Fifty-eight early postmenopausal women attending metabolic bone disease outpatient clinics were randomly allocated into 4 treatment groups and monitored for up to 4 years. All of the patients received 1 gm per day of elemental calcium. One group received percutaneous administration of hormone replacement therapy and another group received intermittent cyclical etidronate. Another group received both of those therapies and the last group received calcium alone. The combined therapies resulted in an increase in bone mineral density of the vertebra of 10.9% and in the femora of 7.25% at 4 years. For the patients treated with the intermittent cyclical etidronate, the increase was 6.79% and 1.2%, while hormone replacement therapy was 6.78% and 4.01% increase in bone mineral density in the vertebra and femora, respectively. The group treated with calcium alone lost 3.81% and 4.96% of the bone mineral density in the vertebra and femora. Patients who received no specific treatment lost 8.58% from the vertebra and 7.83% from the femora over 4 years. This study shows those treated in early menopause had an additive effect of intermittent cyclical etidronate and hormone replacement therapy on bone mineral density in both the hip and vertebra. The combined therapy prevented the occurrence of osteomalacia associated with etidronate. 22846 [ort, end] Benzo(a)pyrenes are polycyclic aromatic hydrocarbons which are associated with cancer. More benzo(a)pyrenes are consumed through food than from smoking. In a rat model the excretion of benzo(a)pyrene in the bile was reduced by water, carbon, quercetin and chlorogenic acid but was potentiated by corn oil. Extraction of benzo(a)pyrene from foods was affected by solvents. It is hypothesized that reduced solubility, physical adsorption and the formation of chemical adducts between benzo(a)pyrene and some food ingredients may play a role in reducing the absorption of benzo(a)pyrene from the gut. These results suggest that benzo(a)pyrene absorption of the intestinal tract is markedly affected by dietary components. Because of this absorption variability, this may be a factor that contributes to the lack of epidemiologic correlation between human cancers and the benzo(a)pyrene content of foods. It is noted that some components of green vegetables such as quercetin and chlorogenic acid inhibit the availability of benzo(a)pyrene, whereas carbon strongly adsorbs benzo(a)pyrene, thereby reducing its bioavailability. 21370 [can, tox] This study evaluated the antioxidant activity and antimutagenicity of green tea, pouchong tea, oolong tea and black Tea extracts. All tea extracts showed marked antioxidant activity and reducing power, especially oolong tea. Oolong tea inhibited 73.6% peroxidation of linoleic acid. Tea extracts exhibited a 65% to 75% scavenging effect on superoxide at a dose of 1 mg, and a 30% to 50% scavenging effect on hydrogen peroxide at a dose of 400 ug. These teas scavenged 100% hydroxyl radicals at a dose of 4 mg, except the black tea. The antioxidant activity and the scavenging effects on active oxygen decreased in the order of semifermented tea to nonfermented tea to fermented tea. Tea extracts showed strong antimutagenic action against 5 indirect mutagens. Oolong and pouchong teas were particularly effective. The antioxidant activity of the tea extracts correlated well with their antimutagenicity in some patients, but varied with the mutagen and the antioxidative properties. 22053[can] In a rabbit model, the animals were given either a standard diet or a diet supplemented with 2.25% L-arginine in their drinking water for 3 days before, and during 4 weeks after, balloon denudation. After sacrificing the animals at 4 weeks, intimal thickening was found to be reduced from .43 mm2 in the control subjects to .24 mm2 in the treated animals. The neoendothelium- dependent relaxation in treated animals was significantly greater than in controls. Endothelium-independent relaxation did not differ between the 2 groups. The authors conclude that L- arginine, which is a precursor to nitric oxide, reduces neointimal thickening after denudation and improves neoendothelial-dependent acetylcholine-induced relaxation. These results support the hypothesis that endothelium-derived nitric oxide may contribute to growth regulation of smooth muscle cells in the vessel wall. 21340 [car] This is a review article on the role of azelaic acid, a naturally occurring saturated 9-carbon dicarboxylic acid, and its effect on hyperpigmentary disorders and acne. Azelaic acid was chosen as a topical drug for treating hyperpigmentary disorders because it possesses a middle-range of antityrosinase activity, is inexpensive and more soluble to be incorporated into a base cream than other dicarboxylic acids. The therapeutic efficacy of azelaic acid has been shown in clinical trials of patients with acne and melasma. Results of these studies suggests that a topical 20% azelaic acid is as effective as a 5% benzoyl peroxide, 0.05% tretinoin, 2% erythromycin and a 0.5-1 g/d per day oral tetracycline in ameliorating comedonal, papulopustular and nodulocystic acne, but is less effective than oral isotretinoin in a dose of 0.5-1 mg/kg per day in reducing conglobate acne. The few encountered side effects of azelaic acid in topical administration and the lack of overt systemic toxicity indicate that its chronic use may be better tolerated than other agents. Topical 20% azelaic acid has been shown to be as effective as 4% hydroquinone cream and superior to the 2% formulation. The lower incidence of allergic sensitization, exogenous ochronosis, or residual hypopigmentation at the application sites produces an advantage over conventional drugs. Azelaic acid may be used as an alternative therapy for melasma in addition to the use of hydroquinone monotherapy or in combination with corticosteroids. Inadequate evidence supports the use of azelaic acid as a primary agent in the treatment of both lentigo maligna and malignant melanoma, but azelaic acid may be considered as an alternative agent when surgical excision and other forms of therapy prove impractical. Patients with multiple sclerosis were found to develop antibodies against endogenous azelaic acid. This compound may show different therapeutic effects when administered to these patients. Azelaic acid is available in Europe in a 20% cream formulation for cutaneous lesions. It can be applied once daily for 1 week and twice daily thereafter for a period of 2 to 3 months up to 1 year. Treatment may be repeated in recurrent cases. In the USA the patent of azelaic acid is currently licensed to Allergen Herbert, Inc. Its therapeutic application in the treatment of skin disorders has not been approved by the FDA. Azelaic acid has not been marketed in the United States, but once released, it would probably be used for acne and melasma. 22019 [der] This was a 9 week study of 12 elderly females who consumed either a 1.47 or a 2.94 gm protein/kg body cell mass per day diet. The mean nitrogen balance in the low protein group remained negative throughout this study. These subjects had significant loss in lean tissue, immune response and muscle function. The adequate protein group was in nitrogen balance throughout the study without changes in lean tissue and with improvements in immune response, serum immunoglobulins, albumin, total protein values and muscle function. Elderly women fed the low protein diet accommodated to the diet by compromising muscle function capacity, whereas those fed the adequate diet maintained functional capacity. The authors showed longitudinal decreases in various functional variables associated with feeding a diet marginal in protein to elderly women. 22756 [nut] This study evaluated total iron, copper, zinc and selenium and the dietary intake of these nutrients in premenopausal and postmenopausal women who mainly had stage I breast cancer and in omnivores and vegetarian controls. Plasma element levels and ratios did not distinguish breast cancer cases from controls. Only for selenium did plasma depend directly on intake. The plasma copper/diet copper ratio distinguished the premenopausal breast cancer patients from the premenopausal controls and the postmenopausal breast cancer patients from the post menopausal vegetarian controls. This study of dietary and plasma elemental levels in pre and postmenopausal women suggests significant differences in nutrition between omnivores and vegetarians, between premenopausal and postmenopausal women, and between breast cancer patients and controls. 21876 [can] This study evaluated in 14 term pregnant women intravenous dehydroepiandrosterone sulfate on ophthalmic artery blood flow. The 200 mg of intravenous DHEA dissolved in 200 mL of 5% dextrose was given. The DHEA had little effect on blood pressure, heart rate, and peak systolic velocity, increasing the mean end-diastolic volume from 3.7 to 4.9 cm/s and the mean averaged peak velocity from 9.8 to 12.1 cm/s. The mean pulsatility index decreased simultaneously. Dehydroepiandrosterone sulfate vasodilates the ophthalmic artery, increasing blood flows in term pregnant females, and possibly similar changes might occur in other cerebral vessels. It is possible that vasodilative effects of dehydroepiandrosterone sulfate may be beneficial in the treatment of preeclampsia. 22844 [gyn, obs, oph] Fractures from osteoporosis are a major public health problem in the western world. Most of the cost calculations are based on hip fractures. The estimates are between 10 and 20 billion dollars annually in the United States and 0.3 billion in England and Wales. These totals are likely to underestimate the cost of the disease. Within 50 years the cost of hip fractures alone in the United States may exceed 240 billion. There appear to be age-specific increases in incidence which will only aggravate the problem. It is not known to what degree interventions can control this epidemic of fractures in the next century. The author says the future is bleak, since in many countries the incidence is increasingly magnifying the effects of societal aging seen currently in most parts of the world. 21933 [end, ort] This study evaluated issues with regards to sports participation in hot or cold environments. These include thermoregulation, heat, cold, fluid replacement and clothing considerations. A core temperature increase as little as 2ø C can cause significant impairment. Treatment for heat cramps include increasing dietary sodium and improved work rest cycles early in training to reduce salt loss via sweating. With regards to heat exhaustion immediate and appropriate therapy will lead to a full recovery. If the athlete is conscious he should be cooled and rehydrated with an oral .1% saline solution. If unconscious the athlete will require intravenous fluid replacement of 5% dextrose, .9% normal saline, .45% sodium chloride or 5% dextrose in .5% sodium chloride along with appropriate cooling measures which include cool towels, wet blankets or cool water applied to the reclining athlete. Treatment for heat stroke includes rapid cooling. Heat stroke has a high mortality and high morbidity rate and rapid cooling can be life saving. A slatted table designed to spray cool water, wet sheets or blankets, fanning or emersion can be used to cool the athlete. Prevention of heat illness means acclamation. Cold injuries can occur during many sports which include trekking, ice skating, hockey, sledding, skiing, snowshoeing, ice climbing and winter camping. The key to treating frostbite is to increase blood flow at the line of demarcation which is the line dividing viable from nonviable tissues. Increasing oxidation at this point can prevent the line from moving farther proximally. Initial treatment should be rapid, rewarming and improving blood flow as proximally as possible. The decision to rewarm the part must be made with some discretion. If there is any chance that the part will become frozen it is best left frozen. The most damage in frostbite occurs during the freeze-thaw-refreeze cycle. If there is a chance that the injured area will refreeze the part should not be warmed but attempts made to prevent further damage. If there is no chance of refreezing any constrictive clothing should be removed and the part rewarmed rapidly. This can be warmed with the palm of the hand, body heat or water between 40 and 43ø celsius. Higher temperatures, open fires, stoves or ovens should not be used because of potential for burn injury. Rubbing the skin can also cause damage to the superficial epithelium. Risk factors of frostbite include a history of frostbite, high winds and low temperatures, improperly fitting clothing and shoes, wet skin, poor circulation, smoking or contact with cold metals. Common sense along with an awareness of risk factors can prevent frostbite. Treatment for the conscious person with hypothermia involves rewarming. Any wet clothing should be removed and the athlete should be wrapped in warm blankets, sleeping bags or additional dry clothing. This allows the shivering mechanism to rewarm the individual. Active rewarming may be used including the use of hot water bottles or heated blankets only to the individual's trunk. Applying heated objects to the extremities can cause the rush of cold blood back to the heart which may cause rewarming shock. The rush of cold acidotic hyperkalemic blood to the core can cause cardiac arrhythmias and fibrillation. When rewarmed and rehydrated the individual should be encouraged to exercise mildly to increase heat production. The unconscious hypothermic is at significant risk of fibrillation. Any jostling or bumping may result in ventricular fibrillation. The athlete should be insulated and transported as quickly as possible. Cardiopulmonary resuscitation is likely to result in asystole. Prevention of hypothermia includes good preparation. Poor preparation is the primary cause of cold related injuries. The addition of blankets, gloves and hats can significantly reduce hyperthermia. The best preparation includes informing someone of exercise course and time of expected return. Staying dry can dramatically decrease the chances of hypothermia owing to the high conductance of water. Sheltering from the wind and wet is very important. 22444 [exe, env] Two female pediatric patients with advanced stage malignant astrocytoma tumors were followed as out patients for 8 weeks on a ketogenic diet. Ketosis was maintained by consuming a 60% medium chain triglyceride oral-based diet. Within 7 days of initiating the ketogenic diet blood glucose levels declined to a low normal level and blood ketones were elevated 20 to 30-fold. Results of the PET Scans indicated a 21.8% average decrease in glucose uptake at the tumor site in both subjects. One patient exhibited significant clinical improvement in mood and new skill development during this study. She continued the ketogenic diet for an additional 12 months remaining free of disease progression. The authors feel that this preliminary result suggests a potential for the clinical application of this diet and merits further research. It is noted that certain tumors, particularly those of the central nervous system rely on glucose as a predominant source of energy. The apparent reason for such glucose dependency is the lack of key mitochondrial enzymes which limits the ability of the tumor to utilize alternative energy sources principally ketones bodies as a major source of fuel. The elevated glucose consumption by the tumor tissue results in a non-productive cycle between the tumor and host draining host energy reserves to provide ATP necessary for increased gluconeogenesis. In theory decreasing the availability of glucose to the tumor would not only be detrimental to the tumor metabolism but disrupt the non-productive energy drain as well. The only way to accomplish this is to switch from a carbohydrate- based to a fat-based ketogenic diet. Results demonstrated that a ketogenic diet containing 14% protein, 16% carbohydrate, 17% medium chain triglyceride oil supplemented with D-3- hydroxybutyrate at 4 mmol E/kg/day induced a ketotic state. At the time of this writing both patients remained in remission at 5 and 4 years after diagnosis respectively. 22120 [can] Two hundred eight individuals who developed stomach cancer and 77 persons who developed lung cancer were evaluated. The average serum levels of selenium and zinc were slightly but not significantly lower among the cancer cases than the controls. The trends in the risk of cancer with decreasing serum levels were neither linear nor significant. Little or no excess risk of stomach cancer was observed among those with the lowest level of selenium or zinc. This data shows a slightly increased risk of lung cancer associated with lower levels of blood selenium, but suggests little association with either lung or stomach cancer across normal selenium and zinc ranges in this Japanese population. 22008 [can] Zinc enhances insulin secretion and insulin sensitivity and can cause insulin-like effects. This study evaluated frequent intravenous glucose tolerance samplings in 7 healthy volunteers (0.5 g/kg of glucose followed by 2 U Insulin injection at 19 minutes) after subjects had taken 20 mg of zinc gluconate the evening before and 30 minutes before the beginning of the test or placebo. Zinc increased glucose assimilation and glucose effectiveness, whereas the insulin sensitivity index and the insulin first-phase secretion did not significantly increase. This study suggests that zinc improves glucose assimilation, and this may occur mainly from an increase in glucose effectiveness or insulin-like effect rather than an action on insulin response or insulin sensitivity. In conclusion, this experiment shows that an acute oral zinc load at physiologic doses improves glucose-induced glucose disposal and improves intravenous glucose tolerance. This effect can be related to the insulin-like effects of zinc, which have been reported at higher supraphysiological doses in animals. 22039 [end] This study evaluated in 80 patients with osteoarthritis of the knee 2 series of 5 intra-articular injections, at 1 week intervals, of 25 mg or .5 ml of glycosaminoglycan polysulfuric acid (GAGPS) into the knee in a double-blind, placebo-controlled trial. There was an immediate decrease in the pain after the injections of 43% with the GAGPS and 33% with the placebo. Pain relief in the GAGPS versus the placebo was not different at other intervals. At 6 weeks the Lequesne Index decreased 20% after the GAGPS and 9% after the placebo. At 10 weeks the Lequesne Index decreased 24% after the GAGPS and 13% after the placebo. The decrease in the Lequesne Index at 13 weeks was 31% after the GAGPS and 15% after the placebo. Other measured parameters tended to be more favorably influenced by the GAGPS than placebo. There was minimal side effects which occurred in approximately 8% of the cases. The authors concluded that GAGPS may play a role as a symptomatic, slow acting drug for osteoarthritis. Future trials of GAGPS should include 50 and 25 mg intra-articularly of GAGPS in 2 treatment course of 5 to 10 injections each given within 1 year to establish a minimal effective dose and toxicity profile. A double-blind study of GAGPS and other osteoarthritic drugs is also warranted. More objective parameters such as magnetic resonance imaging or ultrasound would also benefit the evaluation of this substance in osteoarthritis. 22891 [ost, rhe] Eight children with severe persistent anemia unresponsive to oral iron therapy were treated with intravenous iron saccharate. Hemoglobin rose from 8 g/dL to 11 g/dL. The concentration of serum transferrin receptor, an indicator of iron deficiency, before intravenous therapy, correlated with the increase in hemoglobin. The authors conclude that intravenous iron saccharate could be an effective treatment for chronic anemia in this condition, especially when the iron deficiency is not responsive to oral iron. 22050 [rhe] This is a case report of a 58-year-old white male paraplegic who required the use of a condom catheter for bladder incontinence following an L1 spinal cord injury in 1967. For 25 years he utilized condom catheters derived from rubber tubing, elastic bandages, silicone adhesive and nonlubricated rubber condoms before experiencing recurrent blisters and sloughing of the epidermal layer on the penile shaft. The patient had known allergies to adhesive bandages but no other history of sensitivities to latex or rubber. The patient is using a silicone condom with no latex or other components. The dermatitis has resolved. 22294 [der] In the first part of this study, sperm was taken from 13 fertile nonsmoking men and treated with varying concentrations of nicotine estimated to approach the residual concentrations of nicotine in the testes of heavy, medium and light smokers. The greater the nicotine concentration the more damage to the sperm in terms of shape, motility and linearity. One researcher suggests that males thinking of reproducing should be advised to think about quitting smoking. If they can't quit they should at least try to smoke less than 10 cigarettes per day. When taking washed sperm from 10 fertile, nonsmoking men and mixing it with different concentrations of nicotine it was found that the lower nicotine concentrations resulted in 30% fewer sperm penetrating the egg. When this nicotine concentration was increased to a pack a day the sperm penetration fell 40%. When the concentration simulated a chain smoker there was a 50% decrease. 21384 [gyn, rep, uro] Of evaluating 833 women during 30 randomly selective 4-hour time blocks, 78% participated in this study. The mean age was 34 years and 62% were unemployed. Forty-nine percent had an annual household income of less than $10,000. The incidence of acute domestic violence among the 418 women with a current male partner was 11.7%. Only 23% of these women subjected to acute domestic violence presented for medical care because of trauma. Only 13% told the staff about the domestic violence or were asked about domestic violence by the emergency department professionals. In 230 women without current partners 5.6% reported an episode of domestic violence within the previous 30 days. The cumulative lifetime prevalence of domestic violence exposure was 54.2%. Women exposed to acute or prior domestic violence were more likely than unexposed women to have made suicide attempts and to consume excess alcohol. Women who have experienced domestic violence are seldom identified by emergency room professionals. 22609 [tra] This study was done to evaluate the role of endogenous hydrogen peroxide in cardiac depression and cytotoxicity during hemorrhagic shock and reinfusion. In this dog model cardiac function and contractility were depressed while plasma creatine kinase, creatine kinase-MB activity and lactate increased during shock. Reinfusion after 2 hours tended to return hemodynamic parameters of plasma lactate levels toward control values. Plasma creatine kinase and CK-MB and creatine kinase-MB and polymorphonuclear leukocytes oxygen radical producing activity increased further. Cardiac malondialdehyde concentrations increased after shock and reinfusion. This suggests oxidative damage. Pretreatment with catalase attenuated the adverse effects of shock and reinfusion on the cardiovascular function and contractility. Catalase's protection was not complete. The results suggest that hydrogen peroxide may partly be involved in the deterioration of cardiac function and cellular injury during hemorrhagic shock and reinfusion. 22218 [car, cri, hem] In a recent study in Arteriosclerosis and Thrombosis and Vascular Biology, 1995;15:169-178 it was shown that eggs eaten every day may increase blood cholesterol levels only moderately. This study was funded by the American Egg Board and the National Heart, Lung and Blood Institute. Thirteen women ages 21 through 25 ate either 3 eggs a day, 1 egg a day or a powdered egg substitute in addition to the diet recommended by The American Heart Association. Women followed each of the egg diets for 8 weeks, followed by a washout period between each diet. For every 100 mg of dietary cholesterol added to the diet per day, the total fasting cholesterol concentration increased by 0.073 mmol/L, LDL cholesterol increased by 0.054 mmol/L and the HDL cholesterol increased by 0.015 mmol/L. There were a wide range of responses among the women. Last year, New York researchers found that 20 young men who ate up to 4 eggs per day for 8 weeks had no significant rise in their cholesterol levels. The American Heart Association and the National Cholesterol Education Program recommended a diet that contains no more than 3 or 4 eggs per week. This study seems to indicate that some healthy individuals can pay less attention to their egg consumption if they maintain a low cholesterol level and low heart disease risk profile. However, for most Americans even small adverse effects of dietary cholesterol can increase the overall risk to coronary heart disease. 21927 [car] This is a review by Dr. Robert Russell from the Human Nutrition Research Center on Aging at Tufts University. Trans-fatty acids may have adverse health consequences. Up to 30% of stick margarines are trans-fatty acids. Americans consume 34 to 36% of their total energy as fat. This includes 2 to 4% of the total energy as trans-fatty acids. Studies have shown that high levels of trans-fatty acids can increase LDL cholesterol and lower HDL cholesterol. In the Nurses' Health Study, a higher intake of trans-fatty acids in 70,000 women during an 8 year period showed that trans-fatty acid intake above the 80th percentile was associated with a 50% greater likelihood to develop coronary artery disease than women who consumed less than the 20th percentile. The author states that butter should not be thought of as better than margarine and that the real public message should be to continue a reduced fat and saturated fat diet which reduce trans-fatty acid intakes. Tub margarines may be better than the stick margarines or butter. There was controversy regarding antioxidant supplementation in 2 studies, 1 regarding lung cancer and the other regarding colonic adenomas. In the Finnish study vitamin E at 50 mg per day and beta-carotene at 20 mg per day were taken alone or in combination to prevent the onset of lung cancer among 30,000 male smokers. The supplements were not effective in lung cancer prevention. In fact, statistically more lung cancers occurred among the study participants who received beta-carotene. This received much press. The author states, to his knowledge, there is no other data suggesting the harmful effects of beta-carotene, and there are many other prospective and retrospective epidemiologic studies showing a beneficial relationship between higher carotene intakes or blood levels and a lower risk of lung cancer. The second intervention trial of antioxidants involving beta-carotene, vitamin C and E showed no useful effect in preventing colonic adenoma recurrence. This is not a surprising finding since the epidemiologic data has shown that the possible protective role of antioxidant nutrients against cancer is generally of the upper digestive tract but not cancer of the lower digestive tract. The author states we do not have the final answers regarding the possible protective role of antioxidant nutrients in specific cancers. The role of antioxidants in protecting against other diseases is being defined. The usefulness of calcium and vitamin D supplements preventing osteoporosis is defined better due to recent advances in the areas of nutrition and aging. Twenty-five million people in the United States have osteoporosis which is a major cause of bone fracture in postmenopausal women and the elderly. In a recent study 1700 mg per day of calcium and vitamin D at 800 I.U. were found to have benefit in retarding bone loss from the femoral neck of women 3 to 6 years after menopause. To achieve the 1,000 to 1,500 mg per day recommended calcium intake an increase in low fat dairy products or calcium supplements is required. It was found that aerobic capacity is not the limiting factor to the mobility of elderly people. Lack of muscle strength is the key limiting circumstance. A decline in muscle strength with age has been linked to fear of falling, actual falls and difficulty in getting from the sitting to the upright position. A 1 year study of a high intensity strength training program increased femoral neck bone mineral density, lumbar spinal bone mineral density, muscle mass, muscle strength and balance in postmenopausal estrogen depleted women. Strength maintenance should be an important part of public health strategy. 22585 [nut] This author gave vitamin A at 200,000 I.U. once orally or a placebo randomly to 47 (group I) and 46 (group II) children with chickenpox who had no clinical evidence of vitamin A deficiency. In addition, 8 of the siblings of the first group who had not had the disease received the same amount of vitamin A during the incubation period of varicella 1 to 3 days before the appearance of eruptions in the patients. Crusting of all lesions occurred earlier in the first group than in the second group. The mean duration of diseases was shorter in the 8 siblings than in those who were given the vitamin A during the incubation period of the disease than in the group of children who initially had the disease. Five children in the placebo group had complications. One was viral pneumonia. Two had conjunctivitis or associated infections such as gastroenteritis. But there were no complications in the vitamin A supplemented group. The authors believe that normal children need no treatment of this benign and self-limited disease. However, vitamin A might be given on the first day of eruption to shorten the crusting period and protect against complications. It is much cheaper than antiviral treatment. Vitamin A should be given to more children during the incubation period of the disease to be certain about its effect in varicella. The authors postulate that the role of vitamin A in acute viral disease may not be due to its absolute deficiency but rather its pharmacologic effect. 22196 [inf] This study evaluated 9 nonsmoking men between 23 and 37 years of age regarding the association between exercise intensity and related oxidative stress. The subjects exercised 30 minutes at their aerobic and anaerobic thresholds. The researchers also tested the effect of oral N-acetylcysteine on exercise-associated rapid glutathione oxidation in the subjects performing 2 identical maximal bicycle ergometer exercise tests. Before the second test, the men took 200 mg 4 times per day of N-acetylcysteine tablets for 2 days and an additional 800 mg on the test morning. Blood samples were drawn before, immediately after and 24 hours after the tests. Total and oxidized glutathione levels in the blood were determined. Though there was an association between a single bout of exercise and leukocyte DNA damage, the study suggested that the parameters may not serve as a sensitive index to assess the role of exercise intensity and the extent of exercise-associated oxidative stress. Plasma thiobarbituric acid reactive substances did not change after the maximal bicycle ergometer exercise test or the same exercise test with N-acetylcysteine supplementation. N-acetylcysteine supplementation resulted in an increase in the pre-exercise net peroxyl radical scavenging capacity. Supplementation may have spared exercise-associated blood glutathione oxidation and thiol redox changes. N-acetylcysteine supplementation increased the net peroxyl scavenging capacity of the plasma, indicating that the antioxidant properties of the drug may enhance the net antioxidative capacity of the plasma. It is possible that exercise- associated changes of the blood glutathione redox status may be circumvented by supplementation with N-acetylcysteine. 22023 [exe, met] This discussion suggests that the increased risk associated with abdominal obesity is mediated by increased levels and fluxes of free fatty acids. The article reviews strategies for reducing free fatty acid levels and or flux which include the very low fat, low glycemic index diet which promotes insulin sensitivity via exercise, chromium supplementation, soluble fiber or drugs, antilipolytic agents, the stimulation of hepatic lipid oxidation with hydroxycitrate, carnitine and possibly omega-3 fatty acids. The authors note that when the treatment of obesity appears to be refractory it may be possible to reduce the cardiovascular risk associated with obesity by modulating free fatty acids. 22905 [car, met, obs] This was a cross-sectional study evaluating 99 women, 44 of whom had silicone breast implants. The results of this study showed that silicon-specific T-cell responses were seen in twice as many symptomatic as asymptomatic women exposed to silicone breast implants. This suggests that cell-mediated immunity plays a role in the development of abnormal reactions associated with silicone. This may provide a new, specific screening test. 21661 [aut, rhe] Chlorophyll fed to laboratory animals had the effect of reducing the absorption of heterocyclic amines, polycyclic hydrocarbons and aflatoxins. The green substances also reduced carcinogen binding to DNA in the liver and other organs. Results look promising for cancer prevention. Chlorophyll can inhibit carcinogenesis in the skin. A diet including salad greens, broccoli, spinach and other green vegetables, along with a basic diet which is high in fruits and vegetables, is encouraged. 21901 [can] This study evaluated the pollution of operating-room air by narcotic gasses in 20 hospitals of Niedersachsen. In several cases the limits had been exceeded. Reasons for the increased levels included insufficient room ventilation, defective air-conditioning plants, technical defects and high gas emission due to special techniques in anesthesia such as bronchoscopy. The recommendations include keeping anesthetic gases as low as possible and to increase room ventilation while avoiding unnecessary emissions. 21587 [env, sur] In 1981 it was estimated by Doll and Peto that of all cancer deaths in the United States 30% were due to tobacco, 3% to alcohol and 35% to diet and other causes. Twelve percent of lung cancers were not attributable to tobacco and dietary factors were implicated in the causation of cancer in tissues other than the gastrointestinal tract. Damage to cellular DNA not only occurs from environmental mutagens but also from the endogenous production of oxidants which damage DNA and other mechanisms related to the conversion of food, in particular fats to energy. Inflammation and the healing process can also result in damage. Dietary antioxidants have also been shown to prevent this oxidative cellular DNA damage; these include vitamin A, the carotene family, vitamin C, E and selenium. In reviewing approximately 200 published studies there was overwhelming evidence that the consumption of fruit and vegetables is associated with reduced cancer incidence. In relation to lung cancer, a protective effect was seen in 30 of 32 studies. Infrequent consumers of fruits and vegetables had, on the average, 2.2 times higher incidence of cancer than frequent consumers. Recently a study of Finnish male smokers found that vitamin E and/or beta-carotene supplementation up to 8 years did not reduce the risk of developing lung cancer. One explanation might be that supplementation by the administration of a single pulse dose of vitamin E and/or beta-carotene does not provide protection that the consumption of diets rich in fruits and vegetables and other antioxidants might. Secondly, the trial may have not lasted long enough or might have started too late in the carcinogenic process. Thirdly, in the case of vitamin E, the dose may have been too small. Despite the results of the Finnish trial it remains clear that in any realistic "pie chart" evaluation factors associated with lung cancer risk might include a portion relating to diet. Smokers tend to eat more fat and less antioxidants than nonsmokers. In the case of exposure to environmental tobacco smoke, the dose of smoked chemicals inhaled by nonsmokers are minute compared with those inhaled with active smokers. 21544 [can] This study evaluated 549 mothers who had neural tube defects and 540 controls for vitamin supplements used either 3 months before or 3 months after conception. Their diet was also looked at 3 months before conception. Women with any use of folic acid containing vitamins 3 months before conception had lower risk of having a neural tube defect pregnancy. The odds ratio were similar for 3 levels of average daily intake of folic acid. Any level of use in the first 3 months after conception resulted in a lower risk of neural tube defects. There was modest reduced risk noted in nonvitamin users whose estimated daily intake of folate was more than .227 mg. The authors observed a decreasing risk for neural tube defects with increasing folate intake from combined dietary sources and vitamin supplements. A reduction in neural tube defect risk associated with folate intake is consistent with other studies. The reduction in risk may be more particular for non Hispanic women and women whose education does not exceed high school. 22331 [neu, obs] This study evaluated risk factors in 9,516 women 65 years of age or older who had no previous hip fractures. During the follow-up, which averaged approximately 4.1 years, 192 women had first hip fractures not due to motor vehicle accidents. A maternal history of hip fracture doubled the risk of hip fracture. Women who had gained weight since the age of 25 had a lower risk of hip fracture. The risk of hip fracture was higher in women who had previous fractures of any type after the age of 50, who were tall at the age of 25, who rated their own health as fair or poor, who had previous hyperthyroidism and had been treated with long acting benzodiazepines or anticonvulsant drugs, those who ingested greater amounts of caffeine or spent 4 hours a day or less on their feet. Examination findings suggesting an increased risk to hip fracture include inability to rise from a chair without using oneþs arms, poor depth perception, poor contrast sensitivity or tachycardia at rest. Low calcaneal bone density was also an independent risk factor. The incidence of hip fracture ranged from 1.1 per 1,000 women-years among women with no more than 2 risk factors and normal calcaneal bone density for their age to 27 per 1,000 women-years among those with 5 or more risk factors and bone density in the lowest 3rd for their age. Women with multiple risk factors and low bone density have an especially high risk of hip fracture. Maintaining body weight, walking for exercise, avoiding long acting benzodiazepines, reducing caffeine intake, and treating impaired visual function are important steps that may decrease the risk of hip fracture. It is noted that the finding that caffeine consumption increased the risk of hip fracture agrees with findings of 2 previous studies. 22016 [ger, ort] There are 3 authorized claims with respect to heart disease accepted by the food and drug administration. These include dietary saturated fat and cholesterol, coronary heart disease; fruits, vegetables and grain products that contain fiber, particularly soluble fiber and the risk of heart disease and sodium and hypertension. Approval of a health claim is based on the totality of the publicly available scientific evidence and significant agreement among experts qualified by scientific training and experience to evaluate the particular relationship. On January 4, 1994 the FDA finalized requirements for health claims on dietary supplements. It is noted that the role of omega-3 fatty acids in heart disease is not authorized as well as dietary fiber by itself in heart disease is not authorized. 22347 [car] Two hundred and ninety-seven hypercholesterolemic patients were evaluated for vitamin E, vitamin C and beta-carotene by three 24 hour dietary recall surveys after 3, 6 and 9 months. Saturated fat exchanges were inversely related to intakes of beta-carotene and vitamin E. As the percent of calories from saturated fat decreased there was an increase in vitamin C and beta-carotene. This data suggests that antioxidant intakes can increase on a cholesterol-lowering diet. 22215 [car, nut] Problems which may specifically effect elderly minorities include lack of culturally sensitive, community-based health and social service systems, poverty-related malnutrition and disabilities that make food preparation and acquisition difficult, and lack of easy access to supermarkets. Another area of concern is malnutrition secondary to diseases such as atherosclerosis, cardiovascular disease, renal disease, diabetes mellitus, high blood pressure and certain cancers and forms of obesity. It is noted over 4/5 of older adults have chronic diseases that are affected by diet, 1/5 have confusion or memory loss and þ feel sad or depressed much of the time. These factors all affect appetite, digestion, weight and feelings of well being. Elderly minority group members may not have enough money for food; also, they are less likely to have access to sound advice about special diets, or have extra money for special foods. Poor dental health and poor fitting dentures may also contribute to malnutrition in the elderly poor. Members of minority groups tend to be poor. Poor or older individuals live in less healthful and safe social and physical environments. Over þ of older Americans live alone. Family support networks are often strong in minority groups. But when such networks are not available, elderly minorities may be limited by language barriers, frailty, different values and interests, or prejudice from making new friends or keeping in touch with old ones. Polypharmacy is a problem in older Americans. Nearly half take multiple medications every day. Poor nutrition may be a result of iatrogenic illness due to multiple medication use. One in 5 elderly Americans have difficulties with activities of daily living. Elderly minorities often present later for care and have more severe disease before they get treatment. During the 21st century, the growth of ethnic minorities among the elderly will continue. Nutrition professionals who provide services for these groups must take into account demographic and cultural realities and be more sensitive and responsive to the special needs of minority elders. 21411 [nut] Two hundred and seventy-five elderly individuals living independently were evaluated by cognitive testing at ages 70 and 76 years of age and were interviewed at ages 76 as to their recent life history focusing on special events during the past 6 years. Intellectual abilities were generally found to decline between 70 and 76 years of age. Two-thirds of the subjects had experienced 1 or more life stress situations mostly related to health or bereavement. These results indicated that the decline in cognitive function occurred regardless of life's stressful experiences. The only exception was the bereavement situation of a spouse or a child which seemed to have a marked effect on cognitive abilities. Men seemed to be most vulnerable to this particular stressor. 22471 [ger, neu, psy] This is a review article on the role of homocysteine lowering by specific vitamins and its effect on cardiovascular disease. There is rapidly accumulating evidence that moderate levels of elevated homocysteine are an independent risk factor for cardiovascular disease. All but 5 of 47 studies, including a total of more than 15,000 investigated patients and controls, support this issue. Both basal elevated levels of homocysteine and hyperhomocysteinemia revealed by a methionine load are markers for increased cardiovascular risk. The finding of a dose-response relationship between plasma homocysteine concentration, over its full range, and the relative risk for the prevalence or severity of cardiovascular disease strongly supports causality. Dietary vitamins B6, B12, folate and their synthetic oral counterparts pyridoxine hydrochloride, cyanocobalamin and folic acid serve as precursors of the cofactors for homocysteine metabolism, Pyridoxal 5 Phosphate, methylcobalamin and methyltetrahydrofolate respectively. In man, vitamin B6 deficiency does not seem to result in basal hyperhomocysteinemia. Folate and vitamin B12 deficiency may result in considerable hyperhomocysteinemia which is rapidly normalized after replenishment of the deficient vitamin. Even within the normal ranges, levels of serum or red cell folate and serum vitamin B12 are strong determinants of plasma homocysteine concentrations. In untreated cases of genetically caused severe hyperhomocysteinemias (homocystinuria), life threatening cardiovascular events are frequent. In general, cofactor supplementation for homocysteine metabolism results in considerable decreases of plasma homocysteine concentration. Renal insufficiency results in moderate hyperhomocysteinemia and accelerated atherosclerosis. Several studies have shown that oral treatment with folic acid at 5 to 10 mg per day reduces renal hyperhomocysteinemia by a factor of 30 to 60%. Oral vitamin B6 has no homocysteine lowering effect in this condition. In fact, the authors found that pyridoxine treatment at 300 mg per day for 18 weeks in uremic patients with low plasma pyridoxal phosphate levels lead to significantly increased plasma homocysteine concentrations. In 2 studies which included 28 non- vitamin deficient healthy subjects, mostly with normal plasma homocysteine levels folic acid at 5 mg per day for 2 to 4 weeks resulted in lowering of homocysteine levels in all but 2 of the individuals. Reductions were in the average larger than 30% and were most marked with high homocysteine levels. Oral treatment over 2 weeks with pyridoxine at 40 mg per day or vitamin B12 at 1 mg per day had no homocysteine lowering effect. In another study, vitamin B6 at 120 mg a day had no effect over 6 weeks on plasma homocysteine concentrations in 16 healthy subjects. The authors propose that the homocysteine lowering effect of folic acid in nonfolate deficient subjects is from the excess folic acid after conversion to methyl tetrahydrofolate increases the rate by which homocysteine is remethylated to methionine. In contrast, excess B12 and folic acid will not decrease plasma homocysteine and unless deficiency is present as these vitamins serve as coenzymes, not as cosubstrates as does methyltetrahydrofolate. In 2 recent studies of patients with vascular disease and hyperhomocysteinemia and 1 study in normal normohomocysteinemic patients the combination of vitamin B6 at 100 to 250 mg per day and folic acid at 5 to 10 mg per day reduced plasma homocysteine levels by a mean of 51, 38 and 30% respectively. In a group of consecutive patients with acute myocardial infarction of whom most were normohomocysteinemic and all had normal serum folate levels, we found that 2.5 mg and 10 mg of folic acid over 6 weeks had a similar homocysteine lowering effect in both plasma homocysteine effect. In both groups plasma homocysteine was reduced by a mean of 27%. Reductions were seen in all but 2 patients, both with low homocysteine values. With few exceptions the response to folic acid was proportional to the pretreatment homocysteine levels. Hyperhomocysteinemia due to vitamin B12 deficiency does not respond to folic acid therapy. It has been shown that men with moderate hyperhomocysteinemia in most cases had suboptimal plasma vitamin B12 and folate levels. Such men were in a 6 week trial either given folic acid at .65 mg per day, pyridoxine at 10 mg per day or cyanocobalamin at .4 mg per day or a combination of these vitamins. Most but not all responded to the folic acid. Pyridoxine had no homocysteine lowering effect in this study whereas cyanocobalamin decreased plasma homocysteine by a mean of 15%. All responded to the combination by a mean of homocysteine reduction of 50% though homocysteine values were not normalized in all subjects during this short trial. There are recent results showing that high dose parenteral administration of cobalamin decreases plasma homocysteine in subjects with normal vitamin B12 levels. There have been several studies which show that patients with premature cardiovascular disease frequently respond to oral methionine loads of 100 mg per kg of body weight with abnormally high increases in plasma homocysteine concentrations. This may be more suggestive of a vitamin B6 deficiency compared to an elevated basal homocysteine concentrations which may be more indicative of vitamin B12 and folic acid deficiency which effects homocysteine remethylation. Several studies have shown that pyridoxine at 100 to 250 mg per day improves abnormal methionine loading tests in many but not all patients. With a combination of vitamin B6 at 100 to 250 mg per day and folic acid 5 to 10 mg per day all the patients responded and the abnormality was mostly normalized. Methionine rich meals normally cause slight increases in plasma homocysteine concentrations. It is quite possible that subjects with abnormal methionine loading tests are also responding abnormally to methionine rich meals leading to transient periods of hyperhomocysteinemia which could be normalized with combined pyridoxine and folic acid therapy. For several reasons it appears wise to combine folic acid with vitamin B12. Folic acid seems to reduce all but low homocysteine levels. Cyanocobalamin will probably secure the full responsiveness of folic acid. In vitamin B12 deficiency erroneous treatment with folic acid may correct the hematologic abnormalities but result in a deterioration of vitamin B12 neuropathy. Before starting therapy vitamin B12 deficiency must be excluded and the combination must contain a dose of cyanocobalamin high enough to prevent the occurrence of vitamin B12 deficiency even if complete intrinsic factor deficiency develops during the course of therapy. At least .2 mg of cyanocobalamin need to be administered. For intervention studies in cardiovascular disease a combination of 1 mg of folic acid and .4 mg of cyanocobalamin is probably sufficient for effective homocysteine lowering. This combination will probably be innocuous and also normalized hyperhomocysteinemia in most patients and reduce the normal homocysteine values leading to a shift of the entire homocysteine distribution towards lower values. This is important because there appears to be a relationship between plasma homocysteine concentrations and the risk of cardiovascular disease. 22074 [car] The three most important environmental allergens in the home are dust mites, animal dander and tobacco smoke. Lesser important agents include pollens, molds, cockroaches and various irritants. Elimination of a source is always a solution. Agents that can trigger bronchospasm include airborne allergens, outdoor pollutants, indoor pollutants, cold weather, weather changes, and prescription & over-the-counter drugs containing beta blockers or nonsteroidal antiinflammatory agents. Agents that can induce and sustain inflammation include microorganisms that cause upper respiratory infections, airborne allergens, occupational chemicals, outdoor pollutants, indoor pollutants and tobacco smoke. Measures to minimize dust mite exposure which are essential include: encase mattresses and box springs in zippered plastic cover, encase pillows in zippered plastic cover or wash weekly at 130ø F, wash bedding at 130 degrees water once weekly, avoid lying on upholstered furniture and remove carpets laid on concrete. Things that are desirable include reducing indoor humidity to less than 50%, removing carpets from the bedroom, limit the number of stuffed animals in the bedroom, use miticide on remaining carpets and upholstered furniture, avoid using vacuum cleaners, stay out of a room that is being vacuumed. Use a dust mask if vacuuming has to be done. If possible use a powerful vacuum cleaner, a central vacuum cleaning system or a vacuum cleaner equipped with a HEPA filter. Cost of dust mite control in the bedroom is approximately $42.00 per mattress cover, $10.00 for box spring cover, and $6.00 for pillow case cover; this totals a one-time cost of $58.00 which can reduce dust mite exposure by 95%. Annual cost of treating the carpet is $90.00; it results in about an 85% reduction in dust mite exposure. Also, washing animals once a week can greatly reduce the amount of antigen shedding. 22017 [all, pul] According to the Organic Farming Research Foundation in Santa Cruz, California. The number of organic farms in the United States has remained fairly steady over the last 15 years, between 10 and 12,000 farms. During the early 1980s the 10 to 20 acre farms were more common, now 160 to 3,000 acre farms have become more common. The number of certified organic farms has more than doubled since 1988 from 244 to 528. The states organic farms now managed 50,409 acres up from 16,755 in 1988. Cotton farming, a traditionally heavily pesticide dependent industry, has seen its organic sector grow dramatically in recent years from 150 organically cultivated acres in 1990 to 10,600 acres in 1994. 22998 [foo] In a severely iodine-deficient area, this study evaluated several hundred children from birth to 3 years of age for neurologic development. The prevalence of moderate and severe neurologic abnormalities among the 120 infants whose mothers received iodine in the first or 2nd trimester was 2% as compared to 9% among the 752 infants who received iodine during the third trimester or after birth. The prevalence of microcephaly decreased from 27% in the untreated children to 11% in the treated children. The mean developmental quotient at 2 years of age increased. Treatment in the third trimester of pregnancy or after delivery did not improve neurologic status but head growth and developmental quotients improved slightly. This research shows that up to the end of the second trimester iodine treatment protects the fetal brain from effects of iodine deficiency. Treatment later in pregnancy or after delivery may improve brain growth and developmental achievements slightly though neurologic improvement does not occur. 21549 [end, nut] Marine fish is an important part of the daily diet of the people of Bangladesh. It is also a leading export. The Bay of Bengal zone is a large production zone for fisheries. Marine fishery contributed nearly 20 to 25% of the total production and supplied 80% of the animal protein requirement to the inhabitants of the coastal belt of Bangladesh. In 1992 there was a monitoring program regarding the radioactivity in the marine lives and in costal environmental samples under the auspices of the Ministry of Science and Technology of the government of Bangladesh. The natural radioactivities of 40K, 238U and 232Th and artificial radioactivities of 137Cs and 134Cs were put into tables with regards to the fish in this study. 22958 [env, nut] This is a review article on the role of vitamin E, omega-3 fatty acids and immune function. The omega-3 family has a significant effect on the ability of the immune cells to produce protein and lipid mediators and to exhibit the effector function. The immune changes that occur with omega-3 fatty acids leads to an anti- inflammatory and antisclerotic effect of fish oil. The problem is that there is an increased free radical formation in lipid peroxidation and in the absence of antioxidant protection. Increasing the proportion of fish in the American diet or consuming fish oil supplements without adequate antioxidant protection may increase peroxidation of these omega-3 fatty acids and reduce the beneficial cardiovascular, antiaggregatory and antiinflammatory effects. The potential of omega-3 fatty acids may be an offset by free radical formation in lipid peroxidation including decreased T cell mediated immunity. The risk of consuming omega-3 fatty acids may be minimized without compromising its beneficial effect by appropriate levels of vitamin E consumption. Further studies are needed to determine the adequate level of vitamin E when omega-3 polyunsaturated fatty acid is increased so that the beneficial effects of fish oil can be achieved without its adverse effect on antioxidant systems and T cell mediated function. 22203 [imm] This is a short review on the role of air pollution and health. Key points include that long term exposure to particulate pollution increases mortality. Lower overall levels of pollution may reduce tolerance to acute rises in levels. This could make for difficulties in defining safe levels of air pollution. 21354 [env] This study evaluated 121 patients with initially localized breast cancer for fatty acid content and adipose tissue. A low level of alpha-linolenic acid in adipose tissue was associated with positive axillary lymph node status and the presence of vascular invasion but was not associated with tumor size or mitotic index. After an average of 31 months of follow-up, 21 patients developed metastases. Large tumor size, high mitotic index, presence of vascular invasion and low levels of alpha-linolenic acid were single factors that were significantly associated with increased risk of metastases. Low alpha-linolenic acid and large tumor size were 2 factors that were predictive of metastases. It is noted that the main cause of death in breast cancer patients is the development of the distant metastases. Reduced alpha- linolenic acid in the content of breast adipose tissue is a determinate of metastases in this patient group therefore supplementation of breast cancer patients to replenish stores of alpha-linolenic acid may delay or even prevent the clinical appearance. The mechanisms of alpha-linolenic acid's role in reduction in adipose tissue needs to be determined before dietary intervention is implemented. 22416 [can] In 22 overweight subjects mean age of 39 years there was a positive correlation between plasma homocysteine levels and systolic and diastolic blood pressure, plasma triglycerides and the waist-to-hip ratio. There was a negative association between plasma homocysteine levels and HDL cholesterol, HDL2-cholesterol, HDL3-cholesterol. Homocysteine's association with these known cardiovascular risk factors supports the concept that homocysteine plays an important role in atherosclerosis. 21611 [car] This study evaluated 25 dogs, 10 of which were supplemented with the EPA-ester at 100 mg/kg body weight per day for 8 weeks; 15 served as controls. After ingesting EPA for 8 weeks the ratio of eicosapentaenoic acid to arachidonic acid in platelet cell membranes was significantly increased. The EPA group had a reduction in the chemotactic response of neutrophils to leukotriene B4. Also in the EPA group the amount of 12-hydroxyeicosatetraenoic acid, one of the chemotactic products of arachidonic acid in the infarcted myocardium, was reduced to 40%. EPA treatment resulted in a significant reduction in the ultimate infarct size. In the EPA group the contractile function of the infarcted myocardium was preserved. Myeloperoxidase activity, which is a sign of infiltration of neutrophils into the infarcted myocardium, was less in the EPA group than in the controls. The authors conclude that dietary supplementation with eicosapentaenoic acid inhibits the ischemic myocardial damage through the inhibition of neutrophil infiltration in the damaged heart tissue. 21922 [car] This is a case report of a 6-year-old who was admitted to the hospital with acute gastroenteritis. On physical examination, she was found to have a lesion about 2.5 cm in diameter on her left foot similar to a 3rd degree burn. The lesion healed in approximately 32 days without leaving any scar. It was discovered that the childþs grandmother had placed crushed garlic cloves under a bandage over the effected area for 2 days prior to admission as a remedy for a minor erosion caused by the shoe. The author notes that in addition to this case report there are only 2 other reports of garlic burns. One case was the development of a second degree burn in a 17-month-old after a garlic petroleum jelly plaster had been applied to the skin of both feet for approximately 8 hours. The lesions healed in 2 weeks with topical medication. In another case, a similar second degree chemical burn occurred in a 6-month- old boy; crushed garlic cloves had been applied on both wrists for 6 hours. These burns healed within a 6 week period. It has been suggested that the same factors which cause allergic dermatitis with garlic contact are also the same substances which may produce the burn. These may be diallyldisulphide, allylpropyldisulphide and allicin. 21647 [der, nut, tra] This study, on 2 occasions, evaluated 12 kidney transplant patients with stable cyclosporine trough levels and received grapefruit juice or water every 3 hours for a period of 30 hours. Grapefruit juice increased the peak concentration of cyclosporine by 185 ng/ml. The ratio in the curve of metabolites of cyclosporin related to the inner end of the curve of cyclosporin was reduced by .137 on the grapefruit day. After grapefruit juice there was no other changes seen. The authors conclude that grapefruit juice inhibits the metabolism of cyclosporine for a brief period after administration which may explain why the inhibition of cytochrome P450 enzymes in the gut wall and, to a lesser extent by inhibited of these enzymes in the liver. Grapefruit juice can be a factor in the pharmacokinetics of cyclosporine. 22167 [nep, tran] The exact pathobiochemical mechanism of atherosclerosis and hyperhomocysteinaemia has not been discovered. This data evaluated lipid peroxidation both in vivo and in vitro in 10 homozygous cystathionine synthase-deficient patients and in a control group of 10 healthy subjects. Oxidation resistance, maximal oxidation rate and extension of oxidation of LDL from cystathionine synthase- deficient patients were not significantly different from those of the LDL from controls. The level of thiobarbituric acid reactive substances was lower than in the matched controls. The increased risk of atherosclerosis in hyperhomocysteinaemia is unlikely due to increased lipid peroxidation. 22957 [car] It has been theorized that fecal gram negative bacteria may be provocative agents in the pathogenesis of ankylosing spondylitis and related spondyloarthropathies. Ultra high temperature heating of milk and milk products may still result in bacterial fragments which can play an allergic or activating role on the immune system. Twenty-five outpatients with spondyloarthropathies and 10 with rheumatoid arthritis were told to exclude milk, cheese, yogurt, ice cream and butter from their diet. In the spondyloarthropathy group at 6 weeks there was a relatively good compliance to the diet in 18 of 25 patients. Thirteen of 25 reported good results and 4 of 24 reported moderate improvement. Among the good responders 8 of 13 could discontinue their nonsteroidal anti-inflammatory therapy. Despite good compliance, no patients with rheumatoid arthritis improved at 6 weeks or could reduce nonsteroid anti-inflammatory medications. When followed-up at three months, 12 of 15 spondyloarthropathy responders were satisfied and kept up with the diet; then, ten at 6 months and 8 at 9 months. Six patients over 2 years are still observing the diet and remain free from any other therapy. None has reported discomfort or frustration with the therapy even after this long duration. The conclusion of this study was that more than half of the patients with spondyloarthropathies noted a subjective improvement of their symptoms on a diet without milk products. They felt better, pain severity was decreased, morning stiffness improved, joint and spine symptoms got better and their nonsteroidal anti-inflammatory medication consumption was reduced. A large number of these patients continued on the diet for a longer period. Benefit appeared within 6 weeks and most of the responders decided to keep the therapy up for months to years. Three patients reported a transient relapse of their symptoms within a few days when there was a lapse in their diet; one patient on the diet was free of recurrent episodes of uveitis for over 2 years. The reason for the possible benefits of this diet remain unclear. Digestion is capable of producing a hypersensitivity reaction and certain associations between connective tissue diseases and foods have been suggested. A diet free of dairy products can modify the content of the intestinal flora and reduce the proliferation of pathogenic bacteria. Some gram negative bacterial fragments may persist despite the ultra high heating of processed milk. It is also possible that chronic, intestinal allergy to milk products could contribute to gut permeability alterations in spondyloarthropathies. 21545 [rhe] This is a review article on the role of antioxidants, lipid peroxides in preeclampsia. Several reports have shown that maternal levels of lipid peroxides, vitamin E and antioxidant activity are increased in normal pregnancy as compared with nonpregnancy. This suggests that both peroxidation and antioxidation reactions are increased during pregnancy. Vitamin E levels increase progressively during gestation. Several investigators have reported that maternal levels of lipid peroxides are significantly elevated in preeclampsia. Antioxidant activity in the maternal blood is significantly decreased in preeclampsia as compared to normal pregnancy. The source of increased maternal circulating levels of lipid peroxides in preeclampsia is most likely the placenta since the placenta produces and secretes lipid peroxides. Peroxides, by stimulating cyclooxygenase, can increase the synthesis of both thromboxane and lipid peroxides. Aspirin by inhibiting cyclooxygenase, can decrease the production of lipid peroxides and thromboxane. Thromboxane is a powerful vasoconstrictor and one of the most potent vasoconstrictors of the placental vasculature. Perfusion of the placenta with peroxide results in increased perfusion pressure and increased vascular resistance. Peroxides are not vasoconstrictors, directly, but produce vasoconstriction by stimulating the production of thromboxane. In a normal pregnancy there is a favoring of antioxidant activity over peroxidation with increasing gestation. In preeclampsia there is an imbalance of increased lipid peroxides and decreased antioxidants. This imbalance might explain the clinical and pathophysiologic features of preeclampsia which include the increased thromboxane and decreased prostacyclin production. 22627 [gyn, obs] This is an extensive review article on the role of alcohol in cancer. Alcohol intake appears not to increase the risk of cancer of the lung, bladder, prostate, stomach, ovary, endometrium or melanoma. Alcohol may be a weak causal factor for pancreatic cancer. Alcohol consumption continues to increase the risk for cancer to the mouth, pharynx, larynx, esophagus and liver. The effect of alcohol consumption on cancer of the breast and the large bowel is not clear. 22106 [can] In an ovine model of early osteoarthritis the effects of intra- articular administration of hyaluronic acid on cartilage integrity and the release into synovial fluid of keratan sulfate peptides was evaluated. Five consecutive weekly injections of hyaluronic acid at 2 ml (20 mg) or saline at 2 ml were initiated 16 weeks after the induced osteoarthritis by meniscectomy. In the saline injected animals keratan sulfate peptide levels increased progressively in the synovial fluid relative to the non-operated controls. Keratan sulfate peptide levels in the synovial fluid of the hyaluronic acid group also increased but were not statistically different from controls. The hyaluronic acid injected joints showed less damage than similar regions of the saline animals. The injection of relatively large amounts of highly purified phospholipid free hyaluronic acid into arthritic joints may be an additional source of binding sites for phospholipids and other bioactive molecules. In the absence of the exogenous purified hyaluronic acid inflammatory mediators could stimulate chondrocyte catabolism. The removal of noxious substances from the joint space through the lymphatic system may be a mechanism which could account for the observed reduction in cartilage damage in osteoarthritic joints after intra-articular hyaluronic acid therapy. 22601 [ost, rhe] This is a review article on the role of oxidative stress in neurodegeneration and neurologic diseases such as amyotrophic lateral sclerosis, Parkinson's disease and Alzheimer's disease. The exact cause has remained unknown. It is noted that a unique subset of neurons is effected in each of the 3 diseases even though there are some overlapping similarities. Evidence is accumulating that these diseases result from free radical damage due to oxidative stress. Antioxidant supplementation may be effective therapy and may include such compounds as vitamin E. The most effective treatments for therapy for neurodegenerative diseases may be specific neurotrophic factors. These neurotrophic proteins have had profound benefits in several animal models in promoting the survival and stimulating the neurotransmitter phenotype of those neurons that degenerate in Alzheimer's disease, Parkinson's disease and Amyotrophic lateral sclerosis. These neurotrophic proteins may stimulate specific antioxidant enzyme systems which may help extend the survival of the neuronal tissue. 22251 [neu] Magnesium Sulfate in conjunction with epidural anesthesia is a physiologically appropriate way to inhibit catecholamine release from adrenal tissue with the potential control of intraoperative hemodynamics without additional vascular therapy. This is a case report of a 37-year-old male with aggressive coronary artery disease and hypertension who presented for adrenalectomy and nephrectomy for recently diagnosed pheochromocytoma. During the surgery, along with other anesthetics, the patient was given 5 gm of Magnesium Sulfate IV prior to endotracheal intubation. A pulmonary catheter was placed via the right internal jugular vein and infusions of Magnesium Sulfate at 2 gm per hour as well as Nitroglycerin were given. After 4 hours of surgery, significant ST depression developed without hemodynamic change. Magnesium Sulfate had been discontinued 40 minutes previously and the patient positioned horizontally 20 minutes previously. Appropriate medical therapy was administered. This is the first report of Magnesium Sulfate administration for pheochromocytoma surgery in the United States. Use of magnesium sulfate has been advocated because of direct vasodilitory effect, potent antiarrhythmic properties and especially in the presence of elevated catecholamines and inhibition of catecholamine release from the adrenal medulla, which provides significant advantage over previously used vasodilators. In conclusion, this case highlights successful interoperative hemodynamic management of a patient with pheochromocytoma and severe coronary artery disease solely with magnesium sulfate and epidural anesthesia. This is the first report of the use of magnesium in pheochromocytoma surgery in the United States and supports previously published data and suggests that the combined technique of Magnesium Sulfate and epidural anesthesia is an efficacious approach. 22986 [cad, end] This study evaluated 185 patients with a history of recurrent venous thrombosis in 220 controls for the general population. Homocysteine concentrations were measured before and 6 hours after an oral methionine load of .1 gm of elemental methionine per kg body weight. Hyperhomocysteinemia was defined as homocysteine concentrations above the fasting or the post-methionine value for the 90th percentile of controls. Of 185 patients with recurrent thrombosis 25% had fasting homocysteine concentrations above the 90th percentile or the controls. After adjusting for variables the odds ratio was 2.0. A similar result was found for the post methionine value with an odds adjusted ratio for 2.6. The authors conclude that hyperhomocysteinemia is a common risk factor for recurrent venous thrombosis and can lead to a 2 to 3-fold increased risk. The underlying mechanism by which hyperhomocysteinemia can cause thrombosis is unknown. There is some evidence that homocysteine contributes to endothelial damage in the arterial vessel but it is not clear. Another mechanism may be the in vitro effect of homocysteine on factor V activation and inhibition of thrombomodulin dependent protein C activation. There may be a thrombocyte aggregatory component caused by homocysteine. Elevated homocysteine may result from a hereditary defect in enzymes involved in methionine metabolism or it may be due to a vitamin deficiency. The authors did not find lower levels of folic acid or vitamin B12 in patients more than controls. In fact, higher homocysteine concentrations at a given folic acid concentration were found in patients than in the controls. This may suggest that some form of decreased enzyme activity and not vitamin deficiency leads to thrombosis. Several studies have shown that vitamin supplementation can lower homocysteine levels. Whether vitamin supplementation for those high values of homocysteine will be beneficial with respect to prevention or venous thrombosis has to be further studied. 22141 [car] This study evaluated 33 estrogen-deficient postmenopausal females with a mean age of 59 years to determine if short-term estrogen replacement therapy also improves endothelium-dependent vasodilation in peripheral circulation. Acute intra-arterial infusion of estradiol, which increased forearm venous estradiol levels, potentiated forearm vasodilation induced by the endothelium-dependent vasodilator acetylcholine. The estradiol infusion also potentiated vasodilation induced by the endothelium-independent vasodilator nitroprusside. After 3 weeks of transdermal estradiol administration at 0.1 mg per day, the vasodilator responses to acetylcholine and to sodium nitroprusside were unchanged from initial measurements taken before administration of estradiol. In 8 women receiving transdermal estradiol, a repeat intra-arterial infusion of estradiol increased forearm venous estradiol levels and again potentiated vasodilator response of acetylcholine. The authors note that although acute intra-arterial infusion of 17B-estradiol potentiates endothelium-dependent vasodilation in the forearms of postmenopausal women, this effect is not maintained with a 3-week cycle of systemic estradiol administration. The different effects of acute and chronic estradiol may be due to the lower plasma levels achieved with chronic administration of the medication. Other long-term antiatherogenic effects of estrogen may result in preservation of endothelial function. 21759 [car, gyn] This study reanalyzed the work of Thomas Chalmers in 1975 which suggested that vitamin C had no benefit in treatment of the common cold in the evaluation of 7 controlled trials. This reanalysis suggests that Chalmers' review had shortcomings. Chalmers did not consider the amount of vitamin C used in the studies and included, in his meta-analysis a study utilizing on .025-.05 gm/day of vitamin C to test subjects. In other studies Chalmers used values that are inconsistent with the origin of published results. Using data from the same studies the authors conclude that vitamin C at 1 to 6 gm per day decreased the duration of cold episodes by .93 days; the relative decrease in episode duration was 21%. The present notion that vitamin C has no effect on the common cold seems to be based in large part on a faulty review written 2 decades ago. This present study shows that the Chalmers analysis is fraught with errors and misleading data from the original studies. Studies using at least 1 gm of vitamin C showed quite a consistent benefit whereas studies with smaller doses showed less results. After the Chalmers review was published, a large number of placebo- controlled double-blind studies have been carried out. The results consistently and persuasively support the conclusion that vitamin C supplementation alleviates symptoms of the common cold. Vitamin C has a rational physiologic explanation. Vitamin C may protect against the reactive oxygen species that are produced by phagocytes during a viral infection. Also vitamin C may enhance proliferative responsive T lymphocytes and increase the production of interferon. The authors note that the safety of the general population of long term ingestion of large doses of vitamin C has been firmly established. Diarrhea and other gastrointestinal complaints are sometimes associated with large doses greater than 4 gm per day in healthy people. It is noted that people with a common infection can often ingest 30 gm per day of vitamin C without getting diarrhea apparently due to changes in vitamin C metabolism. There is evidence that large, therapeutic doses of vitamin C which start early in the course of a common cold episode significantly decrease the severity of symptoms. But the evidence showing the benefit of regular intake is much stronger as nearly all of the trials have studied the effects of regular intake. 22115 [inf, nut] This article is a general review article reviewing the role of blood pressure, cigarette use, atherosclerosis, atrial fibrillation, diabetes mellitus, cholesterol and alcohol and the risk of stroke. In general, the increased incidence or use of all these factors are a risk factor to stroke. 22781 [car, cer] This study was to establish blood characteristics of vitamin E status and correlate them between mother and fetus during gestation. Twenty-four pregnant females were evaluated because of a suspicion of toxoplasmososis or other diseases and malformation or intrauterine growth delay which justified cord blood puncture. There was no correlation in plasma vitamin E in the whole population and in the high lipoprotein (a) and low lipoprotein (a) groups, between the mother and fetus. There was a statistically significant correlation between maternal and fetal red blood cell contents and red blood cell relative charges in vitamin E in the whole population, whereas still higher correlations occurred in the high lipoprotein (a) group. Improved correlations were found in the high lipoprotein (a) group for the interrelationship between vitamin E and plasma lipid contents. Improvement was noted in the low lipoprotein (a) group by positive correlation between age and vitamin E red blood cell content or red blood cell relative charge. The authors conclude that evaluation of red blood cell vitamin E and plasma lipoprotein (a) in mothers could be a useful and antenatal blood analysis in cases of risk of prematurity at birth, to prevent peroxidative membrane damage in neonates, and 85% of the mothers in the current population would benefit from vitamin E supplementation from the viewpoint of fetal red blood cell vitamin E requirement in spite of the rather high maternal lipid normalized vitamin E plasma content. 22987 [gyn] This study evaluated the effect of feeding 8 healthy young women a high protein diet of 1.55 g/kg body weight on vitamin B6 status. The 8 healthy women were in a metabolic unit and went on a depletion diet of less than .05 mg of B6 per day for 11 to 28 days followed by either animal-protein or plant protein diets with successfully increasing vitamin B6 intake at .5, 1.0, 1.5 and 2.0 mg/d for periods of 14 to 21 days. Animal protein sources were primarily from dairy and poultry while plant sources were primarily from beans. The plant protein diet does not elevate the vitamin B6 requirement over that required for the animal protein diet given the high amount of dietary protein used in this study. It was also found that .015 mg of vitamin B6 per gm of protein intake normalized most biochemical indices of vitamin B6 status including functional assessment. .020 mg/kg protein normalized all biochemical measures except for total urinary B6. Adding a margin of safety to either the .015 or the .020 mg/g protein intake would raise the vitamin B6 requirement for young women above the current recommended dietary allowance of .016 mg/g of protein. 22308 [nut] This study evaluated sudden, unexpected, infant deaths in Tasmania from April 1993 to 1994 and observed that 3 of the 14 babies or 21% had been found in a waterbed at the time of death. Four case reports were given. These cases highlight the importance of the death scene investigation in all Sudden Infant Death Syndrome cases. The United States Consumer Product Safety Alert includes a warning that infants 12 months or younger can suffocate while sleeping when they sink into a waterbed mattress while on their stomachs. The authors recommends caution in those caring for infants regarding the potential danger of letting infants sleep on an adult free-flow waterbed. 22276 [ped] This study evaluated all cases of SIDS in Tasmania, Australia between 1975 and 1992. Of the 5,534 infants included in this study, 39 later died of SIDS. The Tasmania SIDS rate decreased from 3.8 deaths per 1,000 live births from 1975 through 1990 to the rate of 1.5 deaths per 1,000 live births in 1991 through 1992. The SIDS mortality rate in the cohort by the period of birth was 7.6 deaths per 1,000 live births for those born from May 1, 1988 through April 30th, 1991 and 4.1 deaths per 1,000 infants for those born from May 1st, 1991 through October 31st, 1992. The prevalence of usual prone sleeping position at 1 month of age was 29.9% and 4.3% in these 2 cohorts respectively. Seventy percent of the SIDS rate reduction in the cohort could be accounted for by the decreased prevalence of the prone sleeping position. Other factors individually contributed less than 10% of the SIDS rate reduction. The authors conclude that the major contributing factor to SIDS rate decline in Tasmania has been the reduction in the proportion of infants usually sleeping prone. 21963 [ped] This is a response by Dr. Charles A. Crenshaw, M.D. on JAMA's review of his book by Dennis L. Breo. The book is entitled J.F.K. Conspiracy of Silence. In this letter Dr. Crenshaw states that he stands by his observations some 31 years ago in Parkland's Emergency Room that there was a gunshot wound from the front and that the throat wound was an entrance wound. The wound in the rear of the head was an exit wound as he had reported. He noted that JAMA did not print his 6,800 word article in rebuttal to the JAMA's 11,000 word article. The original article that JAMA refused to publish is scheduled to be published in 1995 by Open Archives Press, of which James Fetzer is an editor. His paper will be presented along with others submitted by the critics of the JAMA's coverage of the J.F.K. assassination. Dennis L. Breo's reply follows this article on page 1633. 22463 [tra] Amyotrophic lateral sclerosis (ALS) occurs in approximately 1 to 2 individuals per every 100,000 each year. It has a similar incidence as multiple sclerosis. ALS is characterized by muscle weakness, wasting, spasticity and weight loss. Death occurs usually within 2 to 5 years of the onset of symptoms. In general the cases are sporadic but about 5 to 10% of the patients have a positive family history. This article reviews the role of glutamate and oxidative stress in this condition. There is abnormal glutamate metabolism in sporadic amyotrophic lateral sclerosis. Glutamate is a neuroexcitatory and toxic amino acid. Individuals with typical ALS have a constellation of signs and symptoms that reflect involvement of the lower motor neurons which include progressive muscle wasting and fasciculations and upper motor neurons which include spasticity and pathological reflexes. In individuals who only have the disease in the limited form only lower motor neurons are considered as suffering from spinal atrophy. There has been a linkage between the disease of several ALS families and the SOD1 gene with the direct sequencing of this gene revealing the presence of 11 point mutations in 13 families. Enzyme activity for SOD1 was reduced by about 50% in the red blood cells of patients with these mutations. SOD1 is an antioxidant enzyme. The altered glutamate metabolism has been shown in patients with primary amyotrophic lateral sclerosis which accounts for the overwhelming majority of patients with motor neuron disease. The mutations of the SOD1 gene are specifically associated with familial ALS. The glutamatergic abnormalities in primarily ALS suggest a defect in membrane permeability and also suggest SOD1 malfunction which might damage membranes via lipid peroxidation. The membrane abnormalities that occur may cause altered presynaptic glutaminergic mechanisms and selective degeneration of the motor neurons. Failure of antioxidant mechanisms appears to enhance neuroexcitotoxic cell damage. Near cell death which is induced by agents capable of generating free radicals is shown to be inhibited by glutamate receptor blockers. It is possible that multiple metabolic abnormalities which can interfere with different aspects of glutamate transmission and/or cellular defenses against oxidative stress may underlie primary amyotrophic lateral sclerosis. 22502 [neu] This is a review article on the role of behavior monitoring and intervention and the secondary prevention of ischemic heart disease. Studies show that anger, depression and anxiety are major factors in the development of ischemic heart disease. Anger is a strong predictor in the development of ischemic heart disease. The resistance to utilizing behavioral modification is not necessarily based on science as much as the resistance is largely due to paradigmatic scotomata, which is conceptual difficulties for those individuals who are not familiar with biopsychosocial research. Routine evaluation of ischemic heart disease patients with psychometric assessment may provide a cost effective way of getting cardiologists and internists to recognize the elevated levels of emotional stress in their patients. It is rare that cardiologists read psychosomatic journals. An alternative is publishing articles relating to behavior and cardiovascular disease in peer review cardiology-type journals. 21539 [car] In 1992, a study reported that women who had breast augmentation had a significantly lower subsequent risk of breast cancer than the general population, with an incidence ratio of 0.48 overall. This paper was a second analysis of the data. Reanalysis found significant differences in the number of person years at risk, resulting in higher standardized incidence ratios than in the original analysis. The final ratios for all breast cancers using Oct. 1, 1973 as the starting date, were 0.76 and 0.85 and 0.68 for induction periods of 0, 5 and 10 years, respectively. None of these standard incidence ratios were significantly different from one. On the basis of the reanalysis, the incidence of breast cancer among women who had breast augmentation could not be said to be either significantly higher or lower than among the general population. 22548 [can] This letter to the editor raises the concern about alfalfa which has been associated with autoimmune hemolytic anemia, systemic lupus erythematosus, and as a trigger for autoimmune disease. This may be caused by the toxic amino acid, L-canavanine, found in alfalfa. Several case reports are cited of individuals who have consumed large amounts of alfalfa over time and subsequently developed autoimmune diseases. There is also concern raised that vitamin E, which has immunomodulatory effects, may possibly be a triggering agent for autoimmune disease. 21475 [aut, nut, tox] This was a retrospective study of 68 familial Mediterranean fever patients with amyloidosis and proteinuria who benefitted while receiving colchicine at a dose of 1.5 mg per day or more. This dosage was only beneficial in patients with initial serum creatinine levels of less than 1.5 mg/dl. These results suggest that amyloidosis of familial Mediterranean fever may be beneficial prior to the onset of the uremic stage to colchicine treatment. 21506 [rhe] This study evaluated 125 Ethiopian immigrants to Israel and found 5 women who had hypocalcemia. All 5 had low serum levels of 25 hydroxyvitamin D3 and high parathyroid hormone levels. In 4 or 5 patients there was evidence of vitamin D deficiency detected during pregnancy or lactation. Treatment with vitamin D2 for 4 to 13 months resulted in clinical improvement and partially corrected the biochemical abnormalities. But low levels of vitamin D and elevated parathyroid hormone persisted. In one case the vitamin D2 therapy was 2000 I.U. of vitamin D orally per day. The authors conclude that vitamin D deficiency among female Ethiopian immigrants to Israel can be due to either dark skin or low calcium and vitamin D intake or possibly both. 22326 [nut, obs] During exercise white blood cells are recruited to the blood. If there is damage to the muscle cytokine levels are increased. After prolonged and extensive exercise the number of lymphocytes in the blood is reduced and the function of natural killer cells is depressed. During this period of time, or the "open window", the host may be more susceptible to micro-organisms bypassing the first line of defense. At rest, trained subjects have slightly elevated nonspecific immunity. During exercise the white blood cells are recruited to the blood. If muscle damage occurs the cytokine level is enhanced. Therefore, short term, time-limited exercise stress induces an inflammatory response. Many top athletes perform frequent severe exercise without giving the immune system time to recover between bouts. For those doing moderate exercise the immune system is enhanced, but there is no "open window" following exercise. 22574 [exe, inf] Twenty-seven patients with activated cirrhosis and aspartate amino-transferase and alanine amino transferase values 2 to 10 times the upper limit of normal were included in this study. Ursodeoxycholic acid given at 600 mg per day in 2 divided doses of 300 mg each or Silymarin at 420 mg per day in 3 divided doses of 140 mg with meals were evaluated. Each patient was given the treatments according to a crossover design with an interval of 1 month between the 6 months treatment. Patients were examined at 3, 6, 7, 10 and 13 months of the trial. The alanine amino transferase levels declined from 175 U/L to 128 and 138 during the 3 and 6 months of the ursodeoxycholic acid. This was a 21% reduction from baseline. The levels were reduced from 201 U/L to 185 and to 155 in the silymarin treated patients at the same time period. This was a 23% reduction from baseline. Similarly the amino transferase values of 114 U/L went to 83 and 80 after 3 and 6 months of the ursodeoxycholic acid therapy, respectively, and from 125 U/L to 118 and 106 during the silymarin treatment. These were not statistically significant. Gamma GT values dropped significantly initially with the ursodeoxycholic treatment but then returned to normal within 6 months. The silymarin treatment did not effect the gamma GT levels. On the average, total serum bile acids increased 5-fold in the ursodeoxycholic treated group whereas they were virtually unchanged after 6 months of silymarin therapy. In conclusion, both the ursodeoxycholic acid and silymarin appeared to be able to reduce the markers of liver cell necrosis in patients with active cirrhosis as judged by the overall 31 to 43% decrease in serum transaminases during the 25 month treatment period. Morover, they do not influence functional liver mass when given alone or in combination. This data does not support the usefulness of giving ursodeoxycholic acid and silymarin together as combination therapy does not appear to be more effective than either drug alone. These substances could represent one of the treatment options in alcoholic cirrhosis and/or in patients with HCV-related liver cirrhosis who did not respond or who were not likely to respond to Interferon therapy. Long term control studies are needed to evaluate the ability of these two cytoprotective agents to prevent the progression of chronic liver disease. 22740 [gas, hep] Selenium dependent and selenium independent glutathione peroxidase activity was evaluated in the cytosolic fractions from malignant and adjacent normal tissue in 13 patients with oral/oropharyngeal and 10 patients with laryngeal squamous cancer. Tumors from the oral/oropharyngeal region contained significantly less selenium glutathione peroxidase and total glutathione peroxidase activity than laryngeal tumors. Primary oral/oropharyngeal and laryngeal tumors had lower selenium glutathione peroxidase activities than matched normal mucosa. Total glutathione peroxidase activities were similar in both normal and tumor tissue. The metastases contained slightly more selenium glutathione peroxidase and total glutathione peroxidase activity than matched tumor tissue. The authors conclude that the inherent anti-tumor drug resistance of human head and neck squamous cell cancer is not mediated by an increased glutathione peroxidase enzyme activity in tumor tissue. This data does not support the hypothesis that glutathione peroxidase plays a role in the resistance of these tumors to anticancer drugs. 22606 [can] Two groups of eight dogs underwent thoracic aortic cross-clamping for 45 minutes. One group received 3 mg per kg intrathecal magnesium sulfate before aortic cross-clamping compared to the controls. Neurologic outcome was statistically better in the dogs who received the magnesium versus those who did not. None of the 8 dogs in the magnesium group had measurable neurologic entry while 7 of the 8 dogs in the control group which did not receive magnesium developed neurologic injury. In conclusion, intrathecal magnesium can prevent spinal cord injury despite significant negative spinal cord perfusion pressure during thoracic aortic cross-clamping in a canine model of spinal cord ischemia. 21558 [car, neu] This study evaluated a meta-analysis of 38 controlled trials between the relationship of soy protein consumption and serum lipid concentrations in humans. Soy protein intake averaged 47 gm per day during the study. Ingestion of soy protein was associated with a 23.2 mg per dl or 9.3% reduction; low density lipoprotein cholesterol decreased by 21.7 mg or 12.9% and triglycerides decreased by 13.3 mg per dl or 10.5%. The ingestion of soy protein was associated with a nonsignificant 2.4% increase in serum concentrations of high density lipoprotein cholesterol. The authors conclude that the consumption of the soy protein rather than animal protein significantly decreases serum concentrations of total cholesterol, LDL cholesterol and triglycerides. There is a nonsignificant increase in HDL cholesterol. Soy estrogens may be responsible for most of this hypocholesterolemic effect. 22969 [car] This study evaluated lipoprotein(a) levels in 40 male patients with thromboangiitis obliterans, 35 patients with ischemic heart disease who had normal angiograms, 123 subjects with arteriosclerosis obliterans, and 203 ischemic heart disease patients with atherosclerotic coronary lesions. A control group of 316 individuals without ischemic heart disease, arteriosclerosis obliterans, or thromboangiitis obliterans was selected. From this control group, 156 subjects without any diseases or abnormal findings in physical examination were selected as the health control group. Lipoprotein(a) levels of arteriosclerosis obliterans and ischemic heart disease with atherosclerotic coronary lesion were significantly higher than those of the control group and healthy control group. The lipoprotein(a) level of the ischemic heart disease with normal coronary angiogram group was significantly higher, at 18.9 mg/dl, than those of the control and healthy control group. Levels of lipoprotein(a) in the thromboangiitis obliterans group were also much higher, at 21.3 mg/dl, than that of the healthy control group. This study suggests that lipoprotein(a) is an independent risk factor for the development of these atherosclerotic diseases. High levels of lipoprotein(a) in patients with cardiovascular disease without atherosclerotic lesions suggest that lipoprotein(a) could also contribute to the pathogenesis of cardiovascular disease by a mechanism different from atherosclerosis. 21762 [car] Fifty-seven patients with gastrointestinal tumors died during follow-up and 43 were still alive at the closing date of the 68 month study. High levels of glutathione S-transferase ã and the glutathione enzyme activity in tumors were found to have a significant prognostic value for the overall survival of these patients. 22951 [can] This study evaluated total homocysteine values in 26 healthy adults; 79 hospitalized patients whose serum vitamin B12 and folate and erythrocyte folic acid levels were greater than 230 pmol/l, 12 nmol/l and 600 nmol/l respectively; 32 hospitalized patients with serum vitamin B12 levels less than 147 pmol/l, compared to 25 patients whose serum vitamin B12 levels were greater than 147 pmol/l but unmatched in any other parameter; and 194 patients whose blood samples were sent for evaluation of vitamin B12 and folate from a neurological service. None of this later group had megaloblastic anemia. There was a relationship between elevated total homocysteine levels in the serum and low values of serum vitamin B12 and erythrocyte folic acid. This relationship was most significant when vitamin B12 levels were less than 86 pmol/L and erythrocyte folate was less than 335 nmol/L. There were some cases of elevated homocysteine in samples where the serum vitamin B12 and erythrocyte folic acid levels were greater than these. There was a poor correlation between serum folate and serum total homocysteine levels. There was a minimal correlation between neutrophil lobation and total serum homocysteine levels. 21566 [hem] Dietary soybean supplementation may be a more acceptable method of estrogen replacement therapy for women. Hormone replacement therapy can protect against atherosclerosis and osteoporosis, but side effects such as moodiness, bloating and increased cancer risk have kept many women from choosing estrogen replacement therapy. Soy estrogens or phytoestrogens are consumed in great quantities in the Asian diet. Asian countries have lower rates of heart disease, breast and endometrial cancer and hip fractures. This study evaluated 80 postmenopausal women consuming 20 gm of soy with phytoestrogens which is approximately 20 mg of phytoestrogens or conjugated estrogens from Premarin. Early results of this study show a beneficial effect on lipids, and a lowering of bone metabolism rates, without having a high adverse effects on vaginal cytology. Primates fed soy protein plus phytoestrogens have lower cholesterol levels than those fed animal protein alone or soy with phytoestrogens removed. There have be no negative effects seen on endometrial cells like with mammalian estrogens which is the suggestive reason for the increase in endometrial cancer rates. 22127 [can, end, gyn ort] In a rat model it was found that moderate exercise may increase the phagocytic capacity of intratumoral phagocytic cells. These changes did not have an effect on tumor incidence or progression in this study. 21446 [can] In 49 premature infants, high plasma vitamin C levels were associated with lower antioxidant status and poor outcome. Plasma antioxidant activity was significantly lower, plasma vitamin C levels were higher, and the vitamin C to ceruloplasmin ratio was significantly higher in the 8 infants who died compared to the 41 survivors. Vitamin C in premature infants may affect the ferroxidase activity of ceruloplasmin. 21653 [obs, ped] Sources of lead exposure to children include lead based paint, lead contaminated soil, house dust, food and drinking water, leaded gasoline, parental occupations and hobbies, industrial emissions, lead-glazed ceramicware, lead-solder cans and some traditional medicines and cosmetics. Ingestion is a primary route of exposure to children. A survey of 43 directors of medical school affiliated lead clinics located in 18 cities concluded that: 1. There is a wide range of blood lead levels for which chelation therapy is recommended. 2. The majority of children with blood lead levels of 1.21 umol/l to 2.17 umol/l (25 ug/dl to 45 ug/dl) with negative CaEDTA provocation tests do not receive chelation therapy. Oral chelating agents are used in the minority of clinics. There is no common approach for the treatment of lead toxicity as present. In the majority of pediatric centers current management of blood lead elevation did not appear to reflect the new information regarding the effects and treatment of lead poisoning. It is noted that meso- 2,3-dimercaptosuccinic acid (succimer) is a promising new oral treatment for lead poisoning. Succimer is a chemical analog of British antilewisite that forms water soluble complexes with lead that are excreted by the kidneys. Succimer is approved only for the treatment of children with blood lead levels greater than 2.17 umol/l (45 ug/dl). Succimer is equally effective as lowering lead levels in children with levels less than 2.17 umol/l (45 ug/dl). The drug has several advantages in that it is orally administered; it is well tolerated with infrequent side effects and it is a relatively specific chelating agent for lead producing less undesired excretion of zinc, copper, iron and calcium EDTA. Health and nutritional counseling is probably the most cost effective means to approach children with exposures less than .97 umol/l (20 ug/dl). Children with lead levels greater than .97 umol/L (20 ug/dL) should receive more involved intervention. Intervention should include reducing the child's body burden and absorption of lead, chelation therapy, treating calcium and iron deficiency and identifying and removing sources of lead. 22187 [env, tox] This study evaluated over 47,000 male professionals between 40 to 75 years of age and found physical activity inversely associated with a risk for colon cancer. Body mass index was directly associated with a risk for colon cancer independently of physical activity. Waist circumference and waist to hip ratio were strong risk factors for colon cancer. Height was also associated with a higher risk for colon cancer. These results suggest an inverse association between physical activity and the risk for colon cancer whereas height and obesity, particularly abdominal adiposity, are associated with an elevated risk. 21988 [can, exe] This was a case controlled study of factors involved in the prevalence of multiple births with at least 1 live born. Over a 15 month period 380 Greek women who had multiple births were compared to 380 live birth singleton pregnancies delivered at the same hospitals for risk factors. Except for an increasing trend with age there were no significant associations between any of the study variables and the occurrence of monozygotic twins. For dizygotic twins there was a weak association with maternal age and height as well as with parity and number of induced abortions. A history of oral contraceptives was inversely but weakly associated with dizygotic twinning. Each cup of coffee per day was associated with an increment in the odds ratio of 1.23-fold. Restricting the analysis to dizygotic twins of different gender increased the point estimate of odds ratio to 1.31 for each cup of coffee consumed daily. There was no association of tobacco smoking with dizygotic twinning after controlling for coffee intake. The mechanism by which coffee has a relationship to dizygotic twinning is not obvious. It is possible that coffee reduces the levels of estrogen and thereby increases the levels of pituitary gonadotropins and ovarian stimulation. Coffee intake reduces pregnancy estrogens. It is possible that coffee intake which is believed to reduce birthweight increases mechanically the probability of a survival of dizygotic and possibly monozygotic twins and the prevalence of their birth. 22328 [obs] This was a double-blind, 4-week trial of 47 patients who received silymarin compared to 50 control subjects who received a placebo. All had slight acute and subacute liver disease, mostly induced by alcohol. There was a statistically highly significant greater decrease of S-SGPT, S-SGOT in the treated group than in the controls. Serum total and conjugated bilirubin decreased more in the treated group than in the controls, but this was not statistically significant. Normalization of histologic changes in the liver occurred more significantly in the treated group than in the controls. Silymarin is extracted from the food of Silybium marianum. It contains 3 isomeric compounds of the phenyl- chromanone group. 22528 [gas, hep] This study evaluated the relationship between dietary intake of fish and mercury, as well as the mercury content of hair and urine to the risk of acute myocardial infarction and death from coronary heart disease or cardiovascular disease. This relationship was evaluated in 1833 men between 42 and 60 years of age who were free of clinical coronary heart disease, stroke, claudication, and cancer. Seventy-three men had an acute myocardial infarction in 2 to 7 years. Of the 78 deceased men, 18 died of coronary heart disease and 24 died of cardiovascular disease. Men who had consumed local nonfatty fish species had elevated hair mercury contents. Dietary intakes of fish and mercury were associated with significantly increased risks of acute myocardial infarction and death from coronary heart disease, cardiovascular disease, and any death. Men in the highest tertile of hair mercury content had a 2-fold higher risk of acute myocardial infarction and 2.9-fold increased risk of cardiovascular death compared to those with lower hair mercury content. The 24 hour urinary mercury excretion had a significant independent association risk of acute myocardial infarction. Both hair and urinary mercury were associated significantly with immune complexes containing oxidized LDL. This data suggests that the high intake of mercury from nonfatty freshwater fish and the subsequent accumulation of body burden mercury are associated with excess risk of acute myocardial infarction and death from coronary heart disease and cardiovascular disease. Mercury may enhance lipid peroxidation and therefore increase risk. The significance of this study is multi-faceted. Fish consumption may be healthy in general, but some fish may contain substances that are not healthy for the cardiovascular system. These findings suggest that mercury, even in subtoxic amounts, is a risk factor for coronary and fatal cardiovascular disease. Increased mercury would increase coronary heart disease by promoting lipid peroxidation. The prevention of additional pollution of the environment by mercury, and the eventual removal of environmental mercury, should be considered as measures in the prevention of cardiovascular disease. 21714 [car] In questioning 834 family medicine residents in 56 residency programs it was found that most reported they had little or no formal training in drug nutrient interactions in medical school (83%) or residency (80%). Seventy-nine percent believed it was the physician's responsibility to inform patients about drug nutrient interactions although many pharmacists (75%) and dieticians (66%) shared this responsibility. Overall residents answered 61% of the 14 drug-nutrient interaction items correctly. There was a slight increase in the drug-nutrient knowledge as the year of residency increased. Nutrition educators need to provide this information in academic settings for the training of health professionals as well as in patient education settings such as hospitals and public clinics. 22118 [med, nut] Epidemiologically there has been an association between thyroid cancer and seafood consumption. Fish consumption can increase the levels of the long chain fatty acids, eicosapentaenoic acid and docosahexaenoic acid. This study evaluated 74 cases of thyroid cancer compared to 221 matched controls. There was an inverse relation between the sum of arachidonic acid and DHA serum concentrations and thyroid cancer risks. In this study high EPA to arachidonic acid ratios, indicating the consumption of fish fat, were not associated with increased thyroid cancer risk. This data suggests that the association between seafood consumption and increased thyroid cancer risk is probably not related to marine fatty acid consumption. 21492 [can] The Certification Board for Nutrition Specialists which was founded by the American College of Nutrition is offering licensing as a certified nutrition specialist for professionals holding advanced degrees from regionally accredited universities. The Board has scheduled its first examination on October 13, 1995 in Washington, D.C.. For more information you may contact the Board at (212)332- 0774. 22355 [nut] This study evaluated 12 men between 20 and 34 years of age who consumed a diet containing 3.5 or 14.5 mg of zinc per day for two 25 day intervals. Deuterium-labeled folic acid at 800 ug per day, or a placebo was given orally during each phase. In this study, short-term folic acid supplementation did not have any adverse effects on zinc status, and the data suggests that folate utilization was not influenced by level of zinc intake. 21747 [nut] This article describes a 2-component prevention strategy to waterborne illness. The strategy allows an individual to disinfect drinking water immediately after collection, and then store the water in a narrow-mouthed, closed vessel designed to prevent recontamination. New disinfectant generators and better storage vessel designs make this strategy practical and inexpensive. This approach enables households and communities that lack potable water to protect themselves against waterborne pathogens and has potential to decrease the incidence of waterborne diarrheal diseases. 21999 [env, inf] This is a case report of an infant with seizures starting soon after birth. They were controlled by intravenous vitamin B6 within 15 seconds after the injection. After 10 minutes the "burst- suppression paroxysms" reappeared on the EEG but not the clinical seizures. The patient was maintained on a daily dose of 10 mg per kg of pyridoxine with complete control of seizures. The pyridoxine dependent seizures are a disorder of GABA metabolism probably due to a defective binding of pyridoxal phosphate coenzyme with glutamine decarboxylase the rate limiting enzyme of GABA synthesis. This results in GABA deficiency resulting in seizures in infancy. There was an increase in the concentration of CSF GABA under pyridoxine therapy. The authors believe that a trial of pyridoxine should be done in all patients with unexplained seizure disorders starting before the age of 14 months. 22302 [neu] This study evaluated 444 individuals of which 185 met the defined PMS criteria. Treatment data was available on 170 individuals. A double-blind protocol in which 300 mg of oral micronized progesterone, .25 mg of alprazolam, or a placebo was given 4 times a day from day 18 of the menstrual cycle through day 2 of the next cycle, including a taper. The mean daily dose at the 3rd treatment was 1,760 mg of progesterone or 1.5 mg of alprazolam. Alprazolam was significantly better than placebo or progesterone for total premenstrual symptoms and DSR factors of mental function, pain and mood. Thirty-seven percent of the alprazolam group experienced a 50% reduction in total DSR scores. There were no clinically significant withdrawal symptoms when alprazolam administration was restricted to the luteal phase. Oral micronized progesterone therapy was no better than placebo. 22757 [gyn] This editorial notes that tobacco leaves contain significant amounts of cadmium. There is evidence that cadmium in tobacco reaches the lens of the eye. It has been shown that cataract lenses from smokers contain much more cadmium than those from nonsmokers. Smokers with or without cataract have higher cadmium levels in their blood. Smokers have lower levels of vitamin C, E and beta-carotene which lower plasma levels of vitamin C, E and beta-carotene which may explain the increased risk to the development of cataracts. In a recent study there was no decreased levels of vitamin C in smokers among either cataract or non-cataract populations nor was there a decreased level of vitamin C in the cataract lens of smokers. These results make it less likely that the causal pathway for smoking to cataracts is via vitamin C. A study by Ramakrishnan favors the idea that cadmium accumulation in the lens directly causes the damage. Other components in tobacco smoke may play a role. Cyanide and thiocyanate levels are raised in the blood of smokers and cigarette smoke is rich in free radicals and aldehydes. These radicals may cause or damage before reaching the lens but isocyanate from cyanide and aldehydes might find their way to the lens to attack the enzymes and other proteins. Isocyanate can cause lens opacification in vitro. Both aldehydes and isocyanate can modify lens proteins causing changes similar to those seen in human cataracts. If cadmium plays a major role in linking smoking to cataract then workers exposed to high cadmium levels in the cadmium plated steel industry, or those consuming cadmium rich food, such as rice in parts of Japan, might have an increased risk of cataract. 22111 [oph] This study found that freeze-dried cells of lactobacilli incorporated up to 400 ug/g of selenium in the presence of 1 ug/mL selenium in the growth medium. At least 80% of the total selenium is associated with organic molecules. Seleno-cysteine was identified as the only seleno-amino acid present in intracellular selenoproteins. This study shows that species of lactic acid producing bacteria are able to concentrate selenium intracellular as seleno-cysteine, which could be utilized in supplementation studies. 22038 [nut] Nineteen subjects were randomized into 2 groups who received either 8 drops of the alpha-galactosidase solution or 8 drops of a placebo. After a test meal these subjects recorded their symptoms for the next 6 hours. One week later an identical test meal was given but the solutions were reversed. Again subjects recorded symptoms for the next 6 hours. The number of flatulence events per hour was significantly less with the group treated with alpha- galactosidase than the placebo over the 6 hour symptom recording period. The authors conclude that oral alpha-galactosidase solution is beneficial for the prophylaxis of gastrointestinal intolerance of oligosaccharides in some patients. 21329 [gas] Four patients with autism who were hitting or poking their eyes were all found to have hypocalcinuria. Three of these patients reduced or stopped their self-injury when they took calcium supplements. Calcium is associated with seizures and also plays an important role in the biosynthesis of neurotransmitters. 22092 [neu] Thirty-nine patients were evaluated by endoscopy. Then, after an overnight fast, blood was drawn and plasma was assessed for ascorbic acid analysis. A nasogastric tube was inserted and a baseline gastric juice sample was obtained; then, 500 mg of vitamin C was injected intravenously. Gastric juice samples were taken in the patients at 30 and 60 minutes after the injection. In this study there were 11 black males, 4 white males, 17 black females and 7 white females. Twenty-four of the patients were infected with helicobacter pylori. Compared to those who were not infected, those who were infected had a smaller increase in ascorbic acid in gastric juice after intravenous injection. These differences were not statistically significant. Whites had significantly greater increases in vitamin C in gastric juice than blacks both at 30 minutes and at 60 minutes. The black- white disparity in vitamin C was independent of helicobacter pylori status and pH. Whites were more likely than blacks to have a large increase in gastric ascorbic acid at 30 minutes and 60 minutes after the injection. When compared with patients with a gastric acid pH of less than 2, patients with a gastric acid pH of 2 or more were less likely to have a large increase of vitamin C at 30 and at 60 minutes. After controlling for variables there was no significant association between helicobacter pylori status and the observed change in vitamin C concentrations in the juice. The differences seen in the transport of vitamin C in the stomach between ethnic groups and at different levels of pH are large and highly statistically significant, despite the small sample size. The helicobacter pylori effect appears to be mediated by its capacity to increase gastric pH, a finding which can be explained by the oxidation of vitamin C in the gastric lumen. Racial and ethnic characteristics appear to play a role in the gastric acid secretion of vitamin C that is independent of helicobacter pylori status and pH, and is therefore probably independent of the changes in the gastric microenvironment brought on by the infection. These findings suggest that both oxidation of vitamin C in the gastric cavity and efficiency of its transport from the blood to the gastric lumen are important. 21902 [can, gas] This study evaluated over 11,000 infants less than 1 month and 1 to 5 months of age with vitamin A supplementation at 50,000 or 100,000 I.U., respectively, or placebo on 4 month mortality in a randomized, double-mass trial in rural Nepal. There were 130 deaths in the control group and 150 deaths in the vitamin A supplemented group which suggests a relative risk of 1.11 which suggests no overall effect on infant mortality. This data suggests that large oral doses of vitamin A to infants less than 5 to 6 months of age may not benefit short term survival. The is data is in contrast to the results of trials in which older infants and children in the same population were supplemented. 22763 [nut] This study evaluated 54 children who had not been previously vaccinated and who were egg allergic. They were given the MMR vaccine in a dose of .5 ml. All 54 children had positive skin testing with egg. Of the 17 children who underwent skin testing with the MMR vaccine 3 had positive results. All 54 children received the MMR vaccine as a single, subcutaneous injection. None had immediate or delayed adverse reactions. The MMR vaccine can be safely administered in a single dose to children with allergy to eggs. 22362[all, inf] In evaluating 4,400 Vietnam veterans it was found that impotence occurred at a 50% higher rate among current smokers than in nonsmokers or past smokers. The rate of impotence in nonsmokers was 2.2%, 2% for former smokers and 3.7% for current smokers. This work was reported in the American Journal of Epidemiology, 1994;140:1003-1008. 21625 [rep] Drugs with a propensity to cause manic symptoms include levodopa, corticosteroids, and anabolic androgenic steroids. Antidepressants of the tricyclic and monoamine oxidase inhibitor classes can induce mania in patients with pre-existing bipolar affective disorders. Other drugs which may induce mania include dopaminergic anti- Parkinsonian drugs, thyroxine, iproniazid and isoniazid, sympathomimetic drugs, chloroquine, baclofen, alprazolam, captopril, amphetamine and phencyclidine. Elimination of the drug or reducing the dosage is the treatment. Treatment of symptoms with lithium may also be warranted. 22264[psy] This study evaluated 74 boxers who received bromelain 2 tablets given 4 times a day for 4 days or until signs of bruising had disappeared compared to 72 who received a placebo. All signs of bruising cleared completely in 4 days in 58 of the supplemented boxers and the remainder cleared in 8 to 10 days. Among the 72 controls at the end of 4 days only 10 had completely cleared. The remainder took 7 to 14 days to completely clear. 22096 [tra, inf] There are 3 authorized claims with respect to heart disease accepted by the food and drug administration. These include dietary saturated fat and cholesterol, coronary heart disease; fruits, vegetables and grain products that contain fiber, particularly soluble fiber and the risk of heart disease and sodium and hypertension. Approval of a health claim is based on the totality of the publicly available scientific evidence and significant agreement among experts qualified by scientific training and experience to evaluate the particular relationship. On January 4, 1994 the FDA finalized requirements for health claims on dietary supplements. It is noted that the role of omega-3 fatty acids in heart disease is not authorized as well as dietary fiber by itself in heart disease is not authorized. 22347 [car] This article reviews 2 case reports of ginseng, which has been used as a tonic in the east for years, and has recently been extended to western society. The first case is a 37-year-old inpatient with a diagnosis of schizophrenia who received a supply of herbal cigarettes which contained ginseng as an active ingredient. The burning of these cigarettes smells similar to marijuana. The individual smoked these cigarettes and had an increased sense of well-being. It was found that 4 patients with schizophrenia followed the individual's example and were regularly smoking ginseng herbal cigarettes which they claimed made them feel good. All the patients were noted to become generally irritable and uncooperative with their treatment programs and overactive with disturbed sleep. This change in behavior corresponded with the time they had been smoking the ginseng cigarettes. When they stopped smoking the cigarettes their symptoms improved. There was no marked change in their psychotic symptomatology. The second case was a 45- year-old male with a long standing history of schizophrenia. The mother, who had died 5 years previously, had been recommending to medical professionals that her son receive ginseng. In one of her letters she encouraged combining the ginseng with A & D fish liver oil capsules. She also stated that ginseng is "a root like a carrot" and not a drug. "You chew the carrot and the ginseng root and add to your health". The doctors did not prescribe the ginseng. This editorial was written to highlight the fact that ginseng and other medicinal plants should not be dismissed as a "harmless health fad" nor condemned as dangerous mixtures of organic chemicals. They should be recognized for their historical importance and their usefulness. Unlike manufacturers' drugs, they are a combination of pharmacoactive substances which have complex interactions that can be difficult to predict. Physicians should inquire about their patients taking these types of substances and inform them of the effects and side effects of herbal products. 21469 [nut, psy] This study evaluated females who had breast implants in the 10 year period allowed for the induction of breast sarcoma. The average number of women in the U.S. who were 10 or more years post breast implantation was 55,000 for 1973-81 and 509,000 for 1982-1990. When the data was evaluated there was a concomitant rise in female breast sarcoma incidence raised between the 2 time periods. The authors found that the mean-adjusted incidence rates of breast sarcoma was .13 per 100,000 women for the initial 9 year period, 1973-1981, and .12 per 100,000 women for the later 9 year period, 1981-1990. Even though the number of person-years at risk was more than 9 times greater in the latter there was no significant increase observed in breast sarcoma rates. The authors conclude there is no evidence of increased risk of breast sarcoma associated with the use of silicone breast implants. 22690 [can] The U.S. Center For Disease Control and Prevention along with the Food and Drug Administration supports the fortification of food with folic acid. The Center For Disease Control believes 350 ug of folic acid per 100 gm of flour should be the norm. The FDA disagrees and has recommended up to 140 ug/100 gm of flour. This is based on the assumption that dietary supplements provide 400 ug of folic acid per unit; many breakfast cereals are fortified with 100 ug per serving. This correlates to a daily intake just below 1 mg per day. The 190 ug difference, according to the Center For Disease Control, may develop into 500 unnecessary affected births per year. Of the 4 million children born annually, there are 2500 cases of neural tube defect. The U.S. Public Health Service estimates that if all women of child-bearing age took 400 ug of folic acid per day, the incidence of neural tube defects would be cut in half. The FDA argues that a higher intake of folic acid may mask an underlying B12 deficiency. The Center For Disease Control says that these risks have been exaggerated. One-third of the very few cases that might develop B12 deficiency would present with neurologic symptoms which would result in a full investigation. In 1993 the Center For Disease Control estimated that only 11 cases of permanent, functional, neurologic deficit could result from a diagnosis of B12 deficiency being delayed versus 1250 cases of preventable spina bifida and anencephaly. In the United Kingdom, the Wolfscon Institute of Preventive Medicine recommended that voluntary or statutory schemes to fortify flour be introduced. The risk to women is in early pregnancy. This risk can be reduced only if a continuous intake of folic acid occurs before conception. 21500 [gyn, neu] Emotions and behavior can effect several risk factors associated with cardiovascular disease. Studies have recently demonstrated the effect of social support in the prevention of cardiovascular morbidity and mortality. Increased neurohormonal activity, specifically in the adrenocortical, sympathetic, and renin- angiotensin systems, caused by stress contributes to endothelial cell dysfunction, which can be the first sign of vascular injury and the first step in the atherosclerotic process. Stress can increase platelet activity, serum levels of epinephrine and norepinephrine, and cholesterol levels. In some patients stress can lead to myocardial ischemia, and is a direct cause of coronary artery vasospasm. Increases in total systemic resistance and heart rate are consequences of perceived stress in many patients. It is noted that anger is the most important factor in a type A personality that can lead to ischemia. Peaks of labile hypertension can be as strong a risk factor for cardiovascular disease as established hypertension. 21416 [car, psy] This study evaluated 181 individuals who had a sedentary life- style and were on drug therapy for hypertension. They were instructed to walk briskly for 40 minutes 3 times per week with or without salt restriction. There was significant reductions of up to 7 mmHg in systolic blood pressure at 3 months for brisk walking alone and salt restriction alone but not for the combined intervention. There was no significant change found for diastolic blood pressure. It was of note, that simple advice on getting some exercise and restricting sodium in a community setting can significantly lower systolic blood pressure at least for 3 months. The absence in benefit after 6 months raises the concern regarding the long term maintenance of life-style changes. This study indicates that it is possible to lower blood pressure, for short periods, in treated hypertensive patients by the prescription of simple advice on physical activity and salt restriction. 22880 [car] At a recent study from the Harborview Medical Center, in Seattle a recent report notes that nearly ¬ of newly admitted patients were vitamin C deficient and only ¬ of the deficient patients received supplementation. In no cases was supplementation given in high enough dosages and/or long enough to replenish the deficient levels. Vitamin C is important in hospitalized patients to enhance wound healing, fight infection, and act as an antioxidant. Needs are increased in individuals who have undergone trauma or surgery as well as those with infections. Vitamin C is inexpensive and nontoxic and it is questioned whether all hospitalized patients should receive enough vitamin C to replenish possible deficiency states without testing their vitamin C status. In this study vitamin C was evaluated from fasting blood samples from 271 patients within 72 hours of admission. The results found low levels in 41% and deficient levels in 23%. Low levels were between .0 and .45 mg/dL and deficient levels were between .2 mg/dl. Only 16 of the 61 patients who were deficient received supplementation. None of these patients had their vitamin C checked prior to supplementation. It was given incidentally. Only 3 of 16 received adequate vitamin C but it was not given long enough to replenish their deficient state. The recommended daily allowance for vitamin C is 60 mg. Hospitalized patients generally require 100 to 200 mg per day. To replenish vitamin C in deficient patients 200 to 1,000 mg per day for 7 days is required. Hospitalized diets may contain the RDA for vitamin C but many patients do not eat all the food they are given. Many hospitalized patients receive multivitamin supplements or prenatal supplements, but they only contain 1 to 120 mg of vitamin C which is not enough to replenish deficient stores. It is noted that Harborview Medical Center is a regional trauma center and county hospital. Private hospitals with fewer trauma cases and more affluent patient populations have a lower incidence of vitamin C deficiency. 22089 [inf, med, sur, tra] This study evaluated the eating patterns in 24 children between 18 and 66 months in relationship to the type of milk beverage and their diet choices. Four different menus were served 3 times during the 6 week period. Each menu came with 8 ounces of the test beverages, which included plain milk, chocolate sucrose-sweetened milk and chocolate aspartame-sweetened milk. It was found that the type of milk did not significantly effect the quantity of food eaten during the meal. 21500 [nut] In animal models it was found that lipid peroxidation and lymphocytes before concanavalin stimulation was significantly less than after stimulation. The SOD promoted the lymphocyte proliferation dose dependently. In the presence of selenium there is an inverse correlation between the levels of lipid peroxide in lymphocytes and the stimulated proliferation. The authors conclude that it is hypothesized that active oxygen species scavenging is one of the main mechanisms for selenium promoting immune function. 22783 [car, imm] The Environmental Working Group reported this week that laboratory tests of 8 baby foods contain residues of 16 different pesticides. These pesticides were found in lower levels than allowed by federal regulators, but the group stressed that pesticide standards are set for adults, not infants. The Environmental Working Group stated it found 16 pesticides in 8 of the 9 baby foods tested, including peaches, applesauce, and sweet potatoes. Gerber dominates the baby food market with a 69% share. A company spokesman for Gerber stated that all their products are safe. The Environmental Working Group statements were similar to that of the National Academy of Sciences for pesticide residue standards that take the health risk to infants into account and recommend the phasing out of possible carcinogenic pesticides. 22998 [env, nut] This study evaluated women with premature ovarian failure. Pregnancy occurred in these individuals in the absence of ovarian function. Concentrations of testosterone and androstenedione were very low if not lower than nonpregnant women. These concentrations were significantly increased in normal pregnancies and were even further increased in human menopausal gonadotrophin-treated cycles. This research shows that the ovary is a contributor to the circulating concentrations of testosterone and androstenedione starting within the cycle of conception. 22453 [rep] This study evaluated 131 patients with cholesterol levels between 5.5 and 8.0 mmol/L on 3 different dietary regimens and life-style interventions. The intervention diets were a pamphlet with brief advice, a group dietary counseling or individual dietary counseling. There was significant lower plasma total cholesterol levels seen at 2 months and 6 months with each of the 3 interventions. Both types of dietitian-based counseling resulted in small but significant decreases in plasma low density lipoprotein cholesterol levels at 6 months in a subset of subjects. There was not a statisticly significant difference in efficacy between the 3 types of intervention. It is noted that dieticians have a role to play in setting up counseling programs. 22897 [car] This patient information sheet encourages eating 5 servings of fruits and vegetables each day. Fruits and vegetables which have high levels of fiber include apples, oranges, broccoli, cauliflower, berries, pears, brussels sprouts, lettuce, figs, prunes, carrots, and potatoes. The replacement of white bread with whole grain breads and cereal, and white rice with brown rice is also recommended. Other high-fiber foods include bran muffins, oatmeal, popcorn, and multi-grain cereals, cooked or dry. Other recommendations include eating dry bran cereal for breakfast, adding 1/4 cup of wheat bran to foods such as cooked cereal, applesauce, or meat loaf, and eating cooked beans each week. 21758 [nut] In induced arthritis in rats the antiinflammatory and antiarthritic activity of Curcuma longa given orally in .01 ml/kg doses was compared to that after cortisone acetate at 10 mg per kg. The inflammatory swelling on the third day after the injection was found to be .32 ml in control rats as compared with .65 and .248 respectively observed in the rats receiving the volatile oil of curcuma longa and cortisone acetate. The late arthritic swelling estimated on day 13 was also significantly less in rats treated with volatile oil of Curcuma longa and cortisone acetate respectively as compared to that observed in the control. The early protective effect of the volatile oil of Curcuma longa is attributed to its antihistamine effect while the activation of the adrenohypophyseal axis by the Curcuma longa oil has been considered for inhibition of late inflammatory arthritic changes. 22140 [rhe] Two new important risk factors for coronary artery disease include lipoprotein (a) and homocysteine. Both are associated with an increased frequency of coronary and peripheral vascular events. It is recommended that these 2 substances be measured in symptomatic patients with coronary artery disease, stroke and a strong family history who have low conventional risk factors; in first degree relatives of those with very high lipoprotein (a) or homocysteine levels; and in individuals who need aggressive treatment of metabolic risk factors. It appears that the risk with high serum lipoprotein (a) levels can be remarkably reduced when one lowers low density lipoprotein cholesterol below 3 mmol/L. Diet, HMG-CoA inhibitors and resins have little effect on lowering lipoprotein (a) levels. Fibrates lower lipoprotein (a) by 5 to 15%, neomycin by 24%, niacin by 38%, neomycin and niacin by 45%, estrogen replacement 14 to 50% and LDL apheresis 40 to 60%. Homocysteine can be easily lowered by doses of vitamin B6 at 250 mg a day and folic acid at 5 mg a day. In resistant individuals the addition of betaine at 3 to 5 gm per day can be added to this regimen. Using the Framingham data, use of total cholesterol to HDL cholesterol ratio and/or the National Cholesterol Education Program II guidelines are the best predictors of future cardiovascular events. The goal of treatment regimen should be to: 1. Lower LDL cholesterol. 2. Decrease serum triglycerides. 3. Increase HDL cholesterol. Niacin plays an important role in these goals. Lowering serum LDL cholesterol to below 2.6 mmol/L results in a slowing progression or advancing regression of disease. Studies with gemfibrozil and niacin and other trials in which combination drug treatments have been utilized show that decreasing serum triglycerides and increasing HDL cholesterol are effective in preventing coronary artery disease. The author suggests that in postmenopausal women hormone replacement therapies should be included in a cardiovascular prevention strategy. The author notes that homocysteine may induce vascular damage by endothelial cell desquamation, reduced platelet survival time, decreased thrombomodulin, reduced protein C activation, increased smooth muscle cell growth, reduced endothelial growth in vitro and intracellular accumulation possibly due to leakage into the plasma. 22620 [car] à-amyrin palmitate which is found in the Ghanaian antiarthritic herbal preparation of Alstonia boonei, Eaies guineensis and Rauvolfia vomitoria was evaluated in an adjuvant-induced arthritic rat model. Fifty-six mg/kg of body weight was given daily for 8 days from 11 to 18 days post adjuvant or at 66 mg/kg body weight for 48 hours for 5 days from days 32 to 40. This herbal medication returned the increases in serum hyaluronate and granulocytes towards non-arthritic levels and corrected the moderate edema of adjuvant arthritis. There was reduced synovial proliferation and invasion of joints and reduced leukocyte infiltration of bone marrow and periarticular tissue in treated rats. This data suggests that à-amyrin palmitate contributes to the previously shown antiarthritic effect of herbal preparations. 22717 [rhe] This study evaluated females who had breast implants in the 10 year period allowed for the induction of breast sarcoma. The average number of women in the U.S. who were 10 or more years post breast implantation was 55,000 for 1973-81 and 509,000 for 1982-1990. When the data was evaluated there was a concomitant rise in female breast sarcoma incidence raised between the 2 time periods. The authors found that the mean-adjusted incidence rates of breast sarcoma was .13 per 100,000 women for the initial 9 year period, 1973-1981, and .12 per 100,000 women for the later 9 year period, 1981-1990. Even though the number of person-years at risk was more than 9 times greater in the latter there was no significant increase observed in breast sarcoma rates. The authors conclude there is no evidence of increased risk of breast sarcoma associated with the use of silicone breast implants. 22690 [can] This study evaluated Type II phospholipase in 23 patients with normal pregnancies and 25 patients with preeclampsia. The mean plasma type phospholipase A2 level in the mild preeclampsia group was not different from the control patients. The mean type II phospholipase A2 level in patients with severe preeclampsia was significantly higher when compared with the other 2 groups. Prostacyclin concentrations in the media of endothelial cells exposed to plasma from patients with preeclampsia were elevated with cells incubated with control plasma. The concentration of type II phospholipase A2 in the condition medium was not significantly different. The authors conclude that plasma concentrations of Type II phospholipase A2 are elevated in preeclampsia and correlate well with the severity of the disease. 22077 [gyn] Two days before tumor implantation, rats were given either glutamine at 1 gm/kg/d or an isonitrogenous amount of glycine. During the three weeks of this study, tumor growth decreased by 40% in the glutamine group. This decrease in tumor growth was associated with a 30% increase in natural killer cell activity. This data shows that oral glutamine supplementation enhances glutathione production and may decrease tumor growth by enhancing natural killer cell activity. 21692 [can, imm] This study evaluated 26 asthmatic children. Twenty were treated with slow release theophylline; there were 6 controls. There was a depression of serum pyridoxal 5'-phosphate in asthmatic children treated with theophylline compared to those not receiving theophylline. There was a significant negative correlation between serum levels of pyridoxal 5'-phosphate and theophylline in the study group. 200 mg of oral theophylline given to 5 children with asthma significantly reduced serum pyridoxal 5'-phosphate levels 4 hours after taking the drug whereas theophylline did not affect the serum pyridoxal levels. The authors conclude that theophylline causes a reduction in circulating pyridoxal 5'-phosphate levels in asthmatic children. 21637 [pul] This article reviews the metabolic effects of dioxin-type chemicals in pesticides and other xenobiotics. The most consistent toxic effects of dioxin-type chemicals are hyperlipidemia, body weight loss, anorexia, changes in carbohydrate metabolism and lipid peroxidation. Dioxin-type chemicals affect lipoprotein lipases, low-density lipoprotein receptors, glucose transporter proteins, vitamin C uptake and insulin secretion. It is suggested that 2,3, 7,8-tetrachlorodibenzo-p-dioxin (TCDD) directly acts with isolated cytosolic aryl-hydrocarbon (Ah) receptor under cell-free conditions even without the presence of the nucleus and is capable of activating key protein kinases that are involved in the growth factor signal-transduction pathway. The resulting activation of the primary-response transcription factors in the nucleus appears to play a role in coordinating vital cell program shifts which include lipid metabolism. 21944 [env, nut] This study evaluated 48 children admitted consecutively for surgical correction of congenital heart disease and found a marked degree of under-nutrition evident in all children. Fifty- two percent had weight less than the third centile, 37% were below the third centile for height and 12.5% were below the third centile for triceps skin fold thickness and 18.8% for subscapular skin fold thickness. Mid-arm circumference and arm muscle circumferences were below the fifth centile in 20.1% and 16.7% of the children, respectively. Five or more of the 29 biochemical and haematological measurements were abnormal in 83.3% of the patients. Ten or more were abnormal in 12.5% of the patients. The authors conclude that children with congenital heart disease are frequently undernourished, regardless of what is the exact nature of the cardiac defect and the presence or absence of cyanosis, a sign of lack of oxygen. 22040 [car] This article reviews the important role of diet in atherosclerosis, coronary heart disease, stroke, hyperinsulinemia, hyperlipidemia hypertension, diabetes mellitus, renal failure, rheumatoid arthritis, osteoporosis and cancer. With regards to cardiovascular disease the type of protein as well as its lipid content, coming from plant versus animal, may be of significance. The type of dietary protein with differing amino acid ratios appears to effect the secretion of insulin. Protein restriction and plant protein may have possible benefit in renal failure in renal disease. Rheumatoid arthritic patients have shown benefit on special types of vegetarian diets. It may be that the high calcium requirements in the Western diet may be due to the increased protein intake. A reduction in protein on a total vegetarian diet may allow for a calcium balance with 1/3 to 1/5 the amount of daily calcium required. Cancer of the breast, colon and prostate have a strong dietary relationship. The incidence of cancer is significantly greater on the modern Western diet than on the vegetarian diet. This may be due to the increased antioxidants, fiber, complex carbohydrate, more unsaturated and less saturated fat along with anticancer components in vegetables, grains, legumes, nuts and fruits. The authors conclude that the western diet appears to be a causal factor in a variety of chronic diseases. The authors feel that a committed lifestyle change with a major shift to a plant food diet appears to be the best way to combat these degenerative diseases. Increased protein availability from plant foods is an important technological improvement especially in developing countries. The authors believe that the food industry will create a variety of foods containing plant proteins, lipids, carbohydrates, fiber and minerals that will be palatable to the western diet-conscious population. 22584 [can, car, end, nut, ost, rhe] This is an extensive review article on breast cancer prevention. Current preventive strategies include avoidance of breast irradiation particularly in adolescents, avoidance of cigarette smoking or passive smoke particularly in adolescents, avoidance of alcohol, avoidance of long duration lactation, avoidance of obesity later in life and prophylactic mastectomy. Breast cancer preventive interventions being evaluated in clinical trials include 4-hydroxyphenyl retinamide, tamoxifen and a low fat diet. Breast cancer approaches in the preclinical evaluation include pseudopregnancy, combination oral contraceptives, LHRH agonist hormonal oophorectomy, and modification of estrogen metabolism. Increased exercise and avoidance of excess calories, especially in adolescents, may delay the onset of menarche. Other preventative interventions being evaluated include growth factor control and ornithine decarboxylase inhibitors. Ornithine carboxylase suppression seems to be an integral part of the reversal of tumor promotion. Other ornithine decarboxylase inhibitors include retinoids and nonsteroidal antiinflammatory drugs. The author notes that the increasing incidence of postmenopausal breast cancer is frustrating and treatment gains have been limited. Progress and widespread prevention has been very slow and the multifactorial etiology of breast cancer development is mostly responsible for the delay. 22668 [can] This study evaluated selenium in serum and hair samples from 20 nonpregnant women, 32 healthy mothers with normal newborns and 28 mothers who had a newborn with neural tube defect at delivery. The mean maternal serum and hair selenium concentrations in the neural tube defect group were 42.9 ng/mL and 7.73 ng/g, respectively, which was significantly lower than those of the control healthy mothers of 50.2 ng/mL and 6.10 ng/g, respectively. The nonpregnant women were also higher than the neural tube defect infant group at 58.1 ng/mL and 315 ng/g, respectively. There was a significant decrease in the concentrations of selenium in serum and hair seen in newborns with a neural tube defect compared with healthy newborns. Those levels were 26 ng/mL and 3.71 ng/g, respectively, in the neural tube defect group and 32.6 ng/mL and 204 ng/g, respectively, in healthy newborns. The mean serum selenium concentrations in 18 of 28 mothers with neural tube defect newborns was significantly lower than the 2 groups of controls. Compared with nonpregnant subjects, mothers who had normal newborns had a significantly lower concentration of serum selenium. The mean serum selenium concentrations was also significantly decreased in 25 women with neural tube defect infants compared with those in mothers with normal newborns and nonpregnant women. The combined action of environmental and genetic factors may be responsible for a group of congenital malformations such as neural tube defects. It is possible that selenium deficiency in mothers interacts with genetic, environmental or other maternal factors to cause this anomaly during early gestation. Another explanation is that lowered serum and hair selenium concentrations were secondary manifestations of an abnormal pregnancy and did not contribute to the neural tube defects. Further study needs to be done to understand why the fall in serum and hair selenium was a manifestation of the underlying abnormality. A study of the importance of selenium in pregnancy and neural tube defects is warranted. 22578 [neu, obs, ped] This article reviews the basis for the role of antioxidants in the prevention of coronary heart disease. There is extensive evidence suggesting a free radical damage and antioxidant defense play an important role on the development of coronary heart disease. Epidemiologic data suggests that antioxidants may be protective but have not unequivocally proven this fact that antioxidant consumption may lead to a decrease in cardiovascular disease risk. The authors feel that long term follow-up intervention studies are still needed to prove the antioxidant hypothesis. They don't believe at this time, that antioxidant supplementation as a preventive measure is justifiable. They do recommend increased consumption of fruits and vegetables. The antioxidants discussed are vitamins E, C and beta-carotene and the mineral selenium which is part of the antioxidant enzyme glutathione peroxidase. There are other antioxidants which include the flavonoids that are present in red wine which have been suggested to account for the French paradox which is the low cardiovascular mortality in France despite the high prevalence of known risk factors. The pro-oxidants iron, zinc and copper may also be involved as well as the intake of unsaturated fatty acids which are most susceptible to oxidative damage. Monounsaturated fatty acids may reduce the oxidizability of LDL cholesterol. 22455 [car] This was a double-blind, 4-week trial of 47 patients who received silymarin compared to 50 control subjects who received a placebo. All had slight acute and subacute liver disease, mostly induced by alcohol. There was a statistically highly significant greater decrease of S-SGPT, S-SGOT in the treated group than in the controls. Serum total and conjugated bilirubin decreased more in the treated group than in the controls, but this was not statistically significant. Normalization of histologic changes in the liver occurred more significantly in the treated group than in the controls. Silymarin is extracted from the food of Silybium marianum. It contains 3 isomeric compounds of the phenyl- chromanone group. 22528 [gas, hep] This article reviews the metabolic effects of dioxin-type chemicals in pesticides and other xenobiotics. The most consistent toxic effects of dioxin-type chemicals are hyperlipidemia, body weight loss, anorexia, changes in carbohydrate metabolism and lipid peroxidation. Dioxin-type chemicals affect lipoprotein lipases, low-density lipoprotein receptors, glucose transporter proteins, vitamin C uptake and insulin secretion. It is suggested that 2,3, 7,8-tetrachlorodibenzo-p-dioxin (TCDD) directly acts with isolated cytosolic aryl-hydrocarbon (Ah) receptor under cell-free conditions even without the presence of the nucleus and is capable of activating key protein kinases that are involved in the growth factor signal-transduction pathway. The resulting activation of the primary-response transcription factors in the nucleus appears to play a role in coordinating vital cell program shifts which include lipid metabolism. 21944 [env, nut] This study evaluated 38 patients who were requiring hemodynamic monitoring due to sepsis. After baseline measurements 19 patients received either 150 mg/kg of n-acetylcysteine or 19 received a placebo and 250 ml of 5% dextrose intravenously over 15 minutes. N-acetylcysteine but not the placebo caused a slight but significant increase in cardiac output and a decrease in systemic vascular resistance. During hypoxia there was a significant difference in the Vo2. N-acetylcysteine was 114 ml/min/m2 versus the placebo at 81 ml/min/m2 and the oxygen extraction ratio for n- acetylcysteine was 21 versus 14 in the placebo. The mean decrease in Vo2 was 11% in the n-acetylcysteine group versus 34% in the placebo group. The mean decrease of oxygen extraction was 12% in the n-acetylcysteine group versus 34% in the placebo group. N- acetylcysteine prevented a decrease in intramucosal pH and hyperoxia. N-acetylcysteine preserved a whole body oxygen uptake, oxygen extraction ratio and intramucosal pH during brief hyperoxia in these septic patients. This data suggests that pretreatment with n-acetylcysteine can prevent, to a certain degree, impaired tissue oxygenation during hyperoxia. 22461 [car, gas] A discriminate analysis involving data from the Scottish Heart Health Study regarding antioxidants in coronary heart disease showed that the combined dietary intakes of the antioxidants C, E and carotene differentiate coronary heart disease prevalence as well as the classical risk factors. In women, step wise discriminate analysis showed that the effect of antioxidant vitamins on coronary heart disease is removed by adjustment for the classical risk factors and aging. The authors concluded that dietary antioxidants appear to have a significant effect on the prevalence of coronary heart disease, especially among men. 22514 [car] Measles exposure early in life may be a risk factor for the development of Crohn's disease. The frequency of Crohn's disease, ulcerative colitis, celiac disease and peptic ulceration was evaluated in 3,545 people that had received live measles vaccines in 1964 as part of the measles vaccine trial. A longitudinal birth cohort of 11,407 subjects was one unvaccinated comparison cohort and 2,541 partners of those vaccinated was another. The relative risk compared to the birth cohort of developing Crohn's disease in the vaccinated group was 3.01 and the development of ulcerative colitis was 2.53. There was no difference in celiac disease prevalence between the 2 groups. There was an increased prevalence of inflammatory bowel disease but no celiac disease or peptic ulcerations found in those vaccinated compared with their partners. These findings suggest that the measles virus may play a part in the development of not only Crohn's disease but of ulcerative colitis. This study shows an association between measles vaccination and inflammatory bowel disease. It does not show a causal relationship. 22302 [gas, inf] Sixteen patients with cardiovascular disease underwent cardiopulmonary exercise testing on a cycle ergometer. Arterial potassium concentrations increased from a baseline of 3.8 to at peak exercise 4.8 mEq. The increase in arterial potassium showed a negative and significant correlation with the percent lactate threshold. There was a good correlation in the rate of fall in potassium concentration during recovery and it is increased during exercise. The authors concluded that in patients with impaired exercise tolerance, the greater the degree of exercise intolerance the greater the increase in arterial potassium during the exercise and a steeper fall in potassium concentration during recovery. When exercise exceeded the anaerobic threshold the rise in potassium concentration during exercise and its fall during recovery were greater. Therefore, exercising below the anaerobic threshold is recommended for patients with cardiac diseases. 22397 [exe] It has been a hypothesis that sugars are a cause of excessive energy intake and obesity. Experimental studies provide evidence that an ingestion of 50 gm of sugar or more within 20 to 60 minutes of a meal resulted in reduced meal time food intake which suggests that appetite regulatory centers respond to sugar's energy content. Epidemiologic data suggests that sugar consumption, as well as carbohydrate consumption, is associated with leanness and not obesity. Studies on the effect of sugar energy and sweetness of food intake do not support the conclusion that sugars have an effect on food intake that is not simply predicted by their energy content. The hypothesis that sugar is unique among carbohydrates because it's hedonic properties override food-intake regulatory controls normally shown by carbohydrate foods remains unsupported. 22765 [nut] Aging alters the metabolism of vitamin D and calcium. There is an age-related decline in the skin production of 7- dehydrocholesterol, the precursor of previtamin D3. Therefore, the synthesis of vitamin D3 in the skin is reduced. Intake of vitamin D from exposure to sunlight, especially the housebound or institutionalized elderly, renal production of 1,25- dihydroxyvitamin D, intestinal absorption of calcium and the ability to adapt to a low calcium diet may all be reduced in the elderly. Researchers also found a decrease in the concentration of vitamin D receptors in the intestinal mucosa in aging women. Secondary hyperparathyroidism may result with aging and may increase the risk to bone loss. Postmenopausal osteoporosis is related to estrogen deficiency and tends to occur earlier between the ages of 51 and 65 than senile (age-related) osteoporosis. In a double-blind, 2-year study of 348 postmenopausal women, 70 years of age or older, in the Netherlands, researchersfound that, compared with placebo, 400 I.U. per day of vitamin D3 increased bone mineral density of the femoral neck. There was no side effect noted. Vitamin D3 significantly increases serum 25- hydroxyvitamin D and serum 1,25-dihydroxyvitamin D, lowered serum immunoreactive parathyroid hormone and increased urinary calcium/creatinine ratio. This study suggests that most individuals were depleted in vitamin D, and that vitamin D3 increased bone mineral density by correcting this depletion and the secondary hyperparathyroidism. In larger studies of nursing home or apartment house bound postmenopausal ambulatory women, 800 I.U. of vitamin D3 and 1,200 mg of elemental calcium given daily for 18 months reduced the incidence of hip fracture by 43% and nonvertebral fractures by 32%, compared with no treatment during the final 6 months of treatment. In another study, annual intramuscular injections of vitamin D2, at 150,000 to 300,000 I.U., reduced the incidence of fractures in elderly Finnish men and women and 1 hydroxyvitamin D3 reduced the incidence of vertebral crush fractures in Japanese women with senile osteoporosis. The authors conclude that due to alterations in vitamin D metabolism and nutrition, which maybe widespread in the aging population, this may play a significant role in the pathogenesis of senile osteoporosis. Treatment with vitamin D and its analogs in modest doses may, in certain cases, prevent the loss of bone mass and fractures in the elderly. 22536 [end, ost] This study evaluated 3 gm of eicosapentaenoic acid in a double- blind, randomized, multi-center study that was given from 12 to 14 weeks of gestation onwards. Sixty-three subjects with a history of intrauterine growth retardation with or without pregnancy-induced hypertension in the previous pregnancy were evaluated. One-third of the women developed pregnancy-induced hypertension and þ of the infants had a birth weight below the 10th centile. There was no difference between the placebo and in the eicosapentaenoic acid group. This study suggests that 3 gm of eicosapentaenoic acid daily does not prevent the recurrence of intrauterine growth retardation or pregnancy induced-hypertension in a high risk population. Future studies should utilize higher doses of EPA preferably in combination with a diet low in arachidonic acid. 22189 [obs, ped] In France fecal incontinence effects approximately 11% of the population or 5 million people. This study evaluated 2 groups of incontinent subjects. The first group was 16 patients mean age of 59.9 years. The second group consisted of 8 patients mean age of 62.2 years. Resting pressure of the upper and lower sphincter, maximum squeezing pressure and duration of contraction were not initially different in groups 1 and 2 but were significantly lower in the control group of patients without incontinence. The biofeedback improved continence at 6 months and at 30 months. The score at 6 months was better suggesting the initial good results may deteriorate over a long period of time. The data suggests that it could be useful to reinitiate biofeedback in some patients. 22273 [gas] This is a case report of a 34-year-old woman who had worsening asthma. She had had asthma since 14 years of age. She married a baker and soon after experienced asthma when working in the bakery. An allergist diagnosed her allergy to wheat flour, so she stopped working in the bakery. The family moved to a house that was located far away from the bakery. Her asthma worsened and, in addition, she had year round rhinitis. Skin prick testing was strongly positive to uncooked aspergillus orizae à- amylase. She also developed a systemic reaction with nasal itching, runny nose and wheezing. She was given a double-blind, placebo-controlled food challenge with à-amylase resulting in coughing, wheezing and a decrease in peak expiratory flow rate. The patient was told to avoid all bakery products containing à- amylase. She followed this advice and her improvement was complete. She had no asthma attacks during the 4 subsequent months. 22047 [all] This study evaluated 28 patients with stress and urge incontinence who utilized biofeedback. Biofeedback successfully treated 5 of 14 patients or 36% with stress incontinence and 9 of 21 patients or 43% with urge incontinence. There was a statistically significant decrease in daytime frequency and nocturia following biofeedback. There was improvement in perineal muscle tone with time. The authors conclude that biofeedback is moderately successful for stress and urge incontinence and should be a modality that is offered to patients as a treatment option. Few patients use biofeedback as a primary mode of therapy. Also the availability of other highly successful treatments for stress urinary incontinence makes this therapy unlikely to be a popular treatment. 22193 [uro] This was a double-blind study of cats with feline pruritic dermatitis. The cats were placed on four weeks of intense flea control. Then, in an 8-week random double-blind test, the cats were given either .5 ml of olive oil as a control or 37 mg of GLA from evening primrose oil. In evaluating pruritus, self-trauma, alopecia and the overall skin condition, no significant differences between the two groups were noted. In this study, the GLA- containing supplement from evening primrose oil had no beneficial effects on signs of feline pruritic dermatitis over olive oil. 21518 [der] Eating foods of plant origin result in low rates of chronic disease and long life expectancies. Research shows that an increase of vegetable, fruit and fiber consumption are associated with lower rates of cancer, coronary heart disease, neural tube defects and cataracts. Carotenoids, folic acid and fiber appear to be all abundant in the Mediterranean diet and play a role in preventing these diseases. There is evidence that a high consumption of full- fat dairy products increases the risk to coronary heart disease. Epidemiologic data does not show that high diary product consumption prevents fractures. Several studies have shown an opposite effect. The authors conclude that the abundant fruit and vegetable and whole grains and low to moderate intake of dairy products in the traditional Mediterranean diet are likely to contribute to the low rates of chronic, degenerative diseases that are seen in this population. 22552 [can, car, end, neu, ost] This study evaluated 24 male volunteers who consumed 50 or 100 mg of elemental zinc from zinc sulfate for 7 days in a randomized, crossover trial with a 3 week washout period. There was a significant increase in 24 hour urinary zinc excretion that occurred after supplementation with 100 mg with a change from 48 mg of zinc/mmol creatinine at day 0 to 82.6 at day 7. There was no significant change seen following supplementation with 50 mg of zinc. This data suggests that urinary zinc excretion is sensitive to only extreme changes in dietary zinc intake. 21862 [nut] This is a review article on the role of fibrinogen and cerebrovascular disease. After blood pressure, fibrinogen is the most important potentially treatable risk factor for ischaemic strokes. Fibrinogen could promote atherothromboembolism: Thrombosis through a hypercoagualable state; the acceleration of atherosclerosis or the reduction of blood flow due to high blood or plasma viscosity. Studies relating fibrinogen levels to the degree of carotid artery stenosis support the accelerating influence of fibrinogen on atherosclerosis. Fibrinogen should be considered as a risk factor for ischaemic stroke and included in the assessment of individual risk factors. For stroke prevention individuals with high fibrinogen values but no other risk factors should be considered for therapies to reduce the overall risk of stroke. These therapies include blood pressure reduction, antiplatelet therapy, regular exercise, weight loss and possibly a vegetarian diet. 22084 [car] Metabolic studies showed that diets high in fat are more likely to result in body fat accumulation than are diets high in carbohydrate. There was no suggestion that simple sugars differ from complex sugars in this regard. Epidemiologic data shows a clear and adverse relationship between sugar and fat. A high intake of dietary fat is positively associated with indexes of obesity, where a high intake of sugar is negatively associated with indexes of obesity. The authors conclude that there is a significant amount of evidence associating high fat diets with obesity but, at present no reason to associate high sugar diets with obesity. 22768 [met, nut] Cryptosporidium parvum is a protozoan which is of concern in AIDS patients and can cause cryptosporidiosis resulting in watery diarrhea. Outbreaks have been noted. Neither chlorine nor standard filtration systems eliminate the organism, so water treatment in virtually all major U.S. cities cannot eliminate it. The EPA is establishing new water purification standards. Large outbreaks of cryptosporidiosis are usually in the spring after heavy rains in areas where there is livestock. Oocysts excreted from the infected animals upstream can quickly exceed the usual levels of C. parvum farther down the water. A recent retrospective study of 194 AIDS patients at San Francisco General Hospital found that 5.8% had cryptosporidiosis at the same time that AIDS was diagnosed. This is noted to be a disease of early HIV infection. Patients with CD4 counts below 54 and hematocrits less than 37 survive an average of 600 days after the diagnosis of cryptosporidiosis. Patients with higher CD4 and hematocrit levels live nearly twice as long. Cryptosporidiosis is usually diagnosed by modified acid-fast stain. The treatment is not very efficacious. A few studies suggest that paromomycin, at least 2 gm a day, is of benefit. One home water filter system that works is the Amway American Filter which uses a reverse osmosis/ultraviolet disinfection mechanism. Carbon filters remove some of the Cryptosporidium parvum but not with certainty. Campers need to take along a 1-um filter. The cost to install a 2-stage filtration system in San Francisco is estimated to be 500 million and in New York City over 1 billion. 22640 [inf] This short review notes that reducing sodium intake and adding citrus based fruit juices to the diet can help prevent kidney stones. A high sodium diet increases urinary calcium and increases crystallization of calcium salts in the urine. Citrus juices bind to calcium and decrease urinary calcium and therefore inhibit crystallization of stones. Citrus juices are a natural alternative to potassium citrate which is used to raise urinary citrate and urinary pH. One has to drink approximately 1 liter per day of orange juice to provide an equivalent alkali load. It is noted, though, that increasing juice intake may increase your oxalate in the urine, so any protective effect of raising urinary citrate may be opposed by the increase in oxalate. Patients may choose to drink citrus juices if they are monitored for increase in urinary oxalate. 21615 [uro] This is an editorial on the role of pollution in asthma. There is little doubt that air pollution can increase the respiratory symptoms in the short and long term. Industrial pollution with sulfur dioxide and smoke does not cause asthma but appears to increase its severity. Diesel exhaust fumes and ozone can enhance the effects of inhaled allergens or have an effect on immune function. The rise in asthma prevalence has coincided with a fall in heavy industrial pollution but an increase in motor vehicle emissions. It is possible that air pollution causes asthma but this hypothesis is far from being proven. Newer pollutants such as ozone PM10 and diesel emissions are suspect. 22565 [all, pul] This study evaluated 10 infants with persistent pulmonary hypertension who were not receiving protein or amino acids for at least 24 hours and compared their plasma arginine concentrations to 8 control infants without persistent pulmonary hypertension receiving similar nutrition. Plasma arginine concentrations were 32 and 52 umol/l in infants with persistent pulmonary hypertension and control infants respectively. There were no other significant differences in the concentration of plasma amino acids. Infants with persistent pulmonary hypertension who were later treated with amino acid infusions had plasma arginine concentrations at 115 umol/l. It is noted that nitric oxide, which has shown some benefit in the treatment of infants with persistent pulmonary hypertension, is synthesized in the body from the amino acid L-arginine. 21408 [ped, pul] This study evaluated 35 consecutive cases of infants who presented with fresh blood mixed with their stools. Out of 34 infants who had colonoscopies and biopsies, 25 had macroscopic colitis and 10 infants had marked, nodular lymphoid hyperplasia. Thirty-one infants had histopathological evidence of colitis characterized by a marked eosinophilic infiltrate. Compared with 19 controls, the mean number of eosinophils per high-power field was greater in patients with colitis. Patients with colitis had an elevated mean absolute peripheral eosinophil count and a low mean serum albumin compared to controls. Out of the 31 infants with colitis, 10 were solely receiving breast milk, 9 cow's milk formula, 9 soy formula, 2 breast milk with cow's milk formula or Nutramigen in 1. Nineteen infants had rapid resolution of frank bleeding and gradual correction of serum albumin with dietary change. Colitis characterized histologically by greater than 20 eosinophils per high-power field is a common cause of rectal bleeding in otherwise healthy infants. Resolution of the bleeding and increase in serum albumin after dietary change suggests this is an allergic colitis. 22009 [all, gas, ped] This study evaluated 8,981 patients with multivessel coronary artery disease who were screened at 8 clinical sites. Three hundred and fifty-nine were randomized to either undergo coronary artery bypass surgery (177 patients) or percutaneous transluminal coronary angioplasty (182 patients). After coronary artery bypass grafting hospitalization was longer and Q wave myocardial infarction in relation to the procedure was more frequent whereas in hospital mortality did not differ significantly between the 2 groups. At discharge 93% of the patients in the coronary artery bypass grafting group were free of angina compared to 82% of those in the percutaneous transluminal coronary angioplasty group. During the first year of follow-up 44% needed further intervention in the angioplasty group but only 6% in the coronary artery bypass group. Seventy-four percent of the patients in the coronary artery bypass group and 71% in the angioplasty group were free of angina after 1 year of treatment. Exercise capacity improved similarly in both groups. Twenty-two percent of the coronary artery bypass group as compared to 12% of the angioplasty group did not require antianginal medication. In selected patients with multivessel coronary artery disease percutaneous transluminal coronary angioplasty and coronary artery bypass grafting as initial treatments resulted in equivalent improvements in angina over 1 year. In order to achieve similar clinical outcomes the patients treated with angioplasty were more likely to acquire further interventions than antianginal drugs whereas the patients treated with bypass grafting were more likely to sustain an acute myocardial infarction at the time of the procedure. 22123 [car] This study evaluated nicotinamide in a human model for its ability to prevent insulin-dependent diabetes mellitus. The authors found that standard nicotinamide given at low doses of 2.5 mg/kg per body weight and Enduramide at 6.7 mg/kg of body weight showed no significant differences in kinetics. A dose of Enduramide at 2 gm resulted in greater bioavailability than the long-acting formulation tested. Metabolic clearance pathways of nicotinamide are saturated at the doses currently used in human trials. Eight adult men with an average age of 20 years and an average body weight of 75 kg were evaluated in this study. Insulin-dependent diabetes mellitus has a prediabetic phase in which there is possibility of medications being administered that can halt the autoimmune destruction of the beta cells. Nicotinamide is a derivative of niacin. It is a weak free-radical scavenger and inhibits interleukin-1B-induced nitric oxide synthase and poly(ADP- ribose) synthetase in islets. Poly(ADP-ribose) synthetase is an intracellular enzyme that repairs DNA strand breaks utilizing NAD as an energy source at the expense of other cell functions. Nicotinamide can prevent alloxan induced DNA strand-breaks which has diabetogenic actions. Nicotinamide at 500 mg/kg body weight also prevents the onset of insulin-dependent diabetes mellitus in spontaneously diabetic mice. Studies in humans with newly onset diabetes have shown only marginal and inconsistent improvements in glucose tolerance with nicotinamide. Nicotinamide is believed to be essentially nontoxic. Its use has been largely restricted to adults. It has been given to humans in a long-acting preparation in a dose of 1 to 3 gm per day, which is equivalent to 15 to 45 mg/kg, some 10 to 33 times less than the dose observed to prevent insulin-dependent diabetes mellitus in animal models. More needs to be learned about this medication at high dose . . . not only in adults, but in children as well. 21752 [end] This study evaluated 481 subjects in 44 geriatric and neurologic units. This was a 150-day trial in 4 different phases. There was a placebo treatment phase for 30 days followed by phase T1 and phase T2 of L-acetylcarnitine (LAC) at 1,500 mg per day for 90 days. Phase T3 included another 30 days of the placebo treatment. There was a significant increase in the total score of the Mini Mental State Examination at the end of the LAC treatment. Memory was also shown to be improved after the LAC treatment. The emotional-affective area showed a significant improvement in total scores as well as the Hamilton Rating Scale. The behavioral- relational aspects evaluated by the Family Stress Scale showed a significant decrease in the total score after treatment. No significant adverse drug reactions were seen during the trial. This study showed a significant improvement in several performance scales in mild mental impairment in the elderly during LAC treatment. 22823 [neu] This study evaluated the plasma cholesterol response to an isoenergetic substitution of a milk chocolate bar (46 grams) given daily for a high carbohydrate snack in healthy men on the Step I National Cholesterol Education Program/American Heart Association Diet. Forty-two normal cholesterolemic men were fed the Step I diet for 21 days followed by a 27 day experimental period in which they consumed the same diet plus either a milk chocolate bar or a high carbohydrate snack. After this they consumed the "run-in" diet for 21 days followed by the other snack for 27 days. When the subjects consumed the milk chocolate bar instead of the high carbohydrate snack, high density lipoprotein cholesterol was .08 mmol/l higher and plasma triglycerides were .06 mmol lower. Substitution of the milk chocolate bar for a high carbohydrate snack did not adversely effect low density lipoprotein cholesterol response to the Step I diet despite an increase in total fat and saturated fatty acid content of the diet. This may be due to the fact that the chocolate contains stearic acid. This data suggests that it is not necessary to reduce the stearic acid content of cholesterol lowering diets. This will lead to fewer restrictions on certain foods and provide greater flexibility in planning diets that lower cholesterol. In a broader context this suggests that a food relatively high in fat containing the appropriate fatty acid profiles may be included in the cholesterol lowering program. 21462 [car, nut] This article reviews the role of moderate hyperhomocysteinemia in the development of atherosclerosis in renal failure patients. In chronic renal failure patients homocysteine levels are significantly elevated at an early stage. The kidney plays a very significant role in homocysteine metabolism but this does not occur in chronic renal failure. There is also a decreased extra renal catabolism, which contributes to the hyperhomocysteinemia state. Five mg of folic acid daily, can significantly lower homocysteine levels in chronic renal failure patients. It is noted that cardiovascular disease is a major cause of death in patients on maintenance dialysis. The deaths from cardiovascular disease with people on dialysis is only partially accounted for by the high prevalence of hypertension, smoking, hyperlipidemia and diabetes. Other nutrients such as pyridoxine at approximately 100 mg and vitamin B12 at 1,000 mcg along with betaine may also be of benefit in lowering homocysteine levels. 22902 [car, nep] This is an extensive review article on the role of vitamin C in gastrointestinal cancer. A comparison of preclinical clinical, clinical and epidemiologic studies suggest that ascorbic acid as an inhibitor of carcinogenesis is stronger to gastric cancer and weaker with regards to esophageal and colon/rectal cancer. There is insufficient data to comment on vitamin C's role in the oral cavity and the use of vitamin C in precancerous conditions such as polyposis. There is some evidence that vitamin C may inhibit the progression of precancerous gastrointestinal conditions to tumors. One example is gastric dysplasias as they relate to helicobacter pylori infection and nitrosamine for production. It may be possible that doses in the recommended daily allowance range may not be effective while pharmacologic doses may exert some benefit. 22950 [can, gas] A magnesium load test was used to diagnose magnesium depletion of 16 critically ill patients. In mean plasma magnesium, red blood cell magnesium, and mononuclear magnesium there was no significant difference between the magnesium depleted group and the nondepleted group. The authors conclude that the diagnosis of magnesium depletion cannot be excluded in the face of normal plasma, red blood cell or mononuclear cell concentrations of magnesium. It is noted that the loading test provides 30 mmol (only 3%) of magnesium in the infusion compared to the body pool of 1000 mmol. Therefore, following the magnesium loading test further infusions of magnesium may be necessary to correct deficiency. This study shows that magnesium depletion as diagnosed by the response to the magnesium loading test, cannot be predicted by plasma, red blood cell or mononuclear blood cell concentrations. This provides further evidence that these parameters do not accurately reflect magnesium in other tissues. 21989 [cri] Twelve patients in the intensive care unit received isonitrogenous and isoenergetic parenteral nutrition over 9 days. The control group received a conventional amino acid solution containing 1.5 gm of amino acid per kg per day and the test group received a complete amino acid solution containing the dipeptide L-alanyl-L-glutamine at 20 gm per liter. Excretion of D-xylose during the 5 hour test period was 7.4 gm in the glutamine supplemented group versus 3.8 in the control group. The 2 hour D-xylose concentration was 38.7 mg/100 ml in the test group versus 27.8 mg/100 ml in the control group. With glutamine dipeptide supplementation there was a high maximum D-xylose blood concentration in higher values for the area underneath the curve. These results give strong evidence that glutamine dipeptide inclusion in total parenteral nutrition prevents intestinal atrophy and increased permeability associated with glutamine-free nutrition. This study shows that daily supplementation of 12-15 gm of glutamine can make up for the increased intestinal need for metabolic fuel during critical illness. 21428 [cri, gas] This study compared 116 cases of bladder cancer to 232 controls for the risk of occupational exposure. There was a significantly elevated odds ratio for exposure to pyrolysis and combustion products. In women, there was an elevated odds ratio for ink exposure. 21594 [can] This study evaluated in 14 term pregnant women intravenous dehydroepiandrosterone sulfate on ophthalmic artery blood flow. The 200 mg of intravenous DHEA dissolved in 200 mL of 5% dextrose was given. The DHEA had little effect on blood pressure, heart rate, and peak systolic velocity, increasing the mean end-diastolic volume from 3.7 to 4.9 cm/s and the mean averaged peak velocity from 9.8 to 12.1 cm/s. The mean pulsatility index decreased simultaneously. Dehydroepiandrosterone sulfate vasodilates the ophthalmic artery, increasing blood flows in term pregnant females, and possibly similar changes might occur in other cerebral vessels. It is possible that vasodilative effects of dehydroepiandrosterone sulfate may be beneficial in the treatment of preeclampsia. 22844 [gyn, obs, oph] The U.S. Department of Agriculture stated that Americans barely passed a new measure of healthy eating. Their healthy eating index took data from the government's continuing survey of food intake by individuals for 1989 and 1990. Over the 2 years the nation scored 64% with 3 out of 4 of those surveyed falling between 50 and 80% on the index, another 15% of respondents falling below and 12% scoring higher. 22998 [nut] This was a cross-sectional study evaluating 99 women, 44 of whom had silicone breast implants. The results of this study showed that silicon-specific T-cell responses were seen in twice as many symptomatic as asymptomatic women exposed to silicone breast implants. This suggests that cell-mediated immunity plays a role in the development of abnormal reactions associated with silicone. This may provide a new, specific screening test. 21661 [aut, rhe] Allergy to natural rubber latex, commonly referred to as latex, was an uncommon occurrence before 1980. In the United States, attention to latex allergy occurred with reports of several fatalities due to anaphylaxis induced by latex retention balloons used in barium enema procedures and by frequent intra-operative anaphylaxis among children with spina bifida. This was attributed to the high prevalence of latex allergy among these children which was probably caused by early and repeated exposure. During the past 5 years there has been increasing evidence accumulating regarding latex allergy as a major occupational health risk. The American College of Allergy, Asthma, and Immunology addresses this concern regarding exposure of health care workers and patients to latex. They suggest; 1. Extractable latex allergen levels. 2. Content labeling of consumer goods. 3. Diagnostic testing. 4. Epidemiologic surveillance. All of these measures are justifiable in terms of patients and employee health and welfare. The cost of initiating these approaches are small. In comparison, the same is expected from reducing the administrative medical, disability, and liability costs of latex allergy. 22985 [all] The effects of Norepinephrine at 4 ug/kg, isoproterenol at 10 ug/kg and phenylephrine at 20 ug/kg were evaluated in an anesthetized dog model with normal plasma magnesium and induced hypermagnesemia. Norepinephrine caused a 24% increase in heart rate and a 103% increase in systemic vascular resistance in normo-magnesemic dogs while the hypermagnesemic dogs had values of 13% and 1%, respectively. Isoproterenol increased the heart rate by 48% and 18% in dogs with normo and hypermagnesemia, respectively. Phenylephrine increased the systemic vascular resistance index by 74% only in the normomagnesemic state. The effects of the drugs were significantly different without and with the simultaneous administration of magnesium sulfate resulting with plasma levels of 1.3 mEq/l and 6.8 mEq/l, respectively. The authors conclude that acute induced hypermagnesemia antagonizes circulatory effects of adrenergic stimulation which may explain the antiarrhythmic and hemodynamic effects during acute myocardial ischemia. 22762 [car, end] This study evaluated 42 patients who were randomized into 2 groups. One group received an isocaloric and isonitrogenous placebo diet and the other group was fed the same diet supplemented with arginine at 1.25 gm per 100 ml, RNA at .12 gm per 100 ml, omega-3 fatty acids at 10.5% per 100 ml and omega-6 fatty acids at 8.3% per 100 ml. In those who received the placebo diet interleukin VI concentrations were significantly higher on days 3 and 7 and tumor necrosis factor alpha concentration on day 7. In contrast mean concentrations of interleukin-II receptor was significantly higher on days 3 and 7 and interleukin-I beta and interleukin-II on day 16 in the groups receiving the supplemental diet. The authors conclude that the diet with supplemented arginine, RNA and omega-3 fatty acids can modulate acute phase reaction as indicated by reduction in concentrations of tumor necrosis factor and interleukin-VI in the group fed the supplemental diet. Patients receiving the supplemental diet showed accelerated recovery in concentrations of interleukin-I beta and interleukin-II receptor. Supplementation of enteral nutrition with arginine, RNA and omega-3 fatty acids improved recovery from immune depression induced by cancer and operation. 22687 [can, sur] Lipoprotein (a) is an atherogenic lipoprotein that resembles LDL cholesterol but has an additional apoprotein (a). Lipoprotein (a) was evaluated in 203 Caucasian subjects with coronary artery disease and in 66 subjects without coronary artery disease. Lipoprotein (a) was elevated in coronary artery disease patients compared to subjects without coronary artery disease. There was no difference between patients that had myocardial infarction as a first sign of the disease and those who had only angina pectoris for 2 years. Plasma lipoprotein (a) levels were correlated with the extent of the disease. In those who had coronary artery disease lipoprotein (a) levels were higher in females. In a smaller group of 29 black subjects it was found that lipoprotein (a) was higher than in Caucasians but there was no difference between the subjects with and without coronary artery disease. The data here shows that lipoprotein (a) levels do not influence the clinical presentation of coronary artery disease. Lipoprotein (a) level were correlated with the extent of the disease. Lipoprotein (a) levels were higher in blacks than in Caucasians but in blacks lipoprotein (a) was not predictive of the disease. Smoking was the most important risk factor for the development of coronary artery disease followed by higher plasma apo (b) and lipoprotein (a) concentrations. 23024 [car] This article is a rebuttal to an article which stated that zinc therapy was not beneficial in burns. It is noted, from the author's experience, that supplementation with large doses of zinc during the first week after substantial thermal burns not only enhances zinc levels, but also enhances recovery by improving wound healing, resulting in a shortened hospital stay. 21503 [der, nut] An increasing number of cases have been reported of systemic sclerosis related to aliphatic hydrocarbons, aromatic hydrocarbons, aromatic amines and formaldehyde. This is a case report of a 56- year-old male who developed systemic sclerosis of the skin, lung and pericardium after intense exposure to toluene, heptane, dimethylbuthylphenyldiamine and octhyphenol formaldehyde. The patientþs treatment included nifedipine at 30 mg per day and prednisone at 1 mg per kg per day. He died 12 months after diagnosis of cardiorespiratory failure. It is noted that organic solvents penetrate the skin, can be inhaled and may produce metabolic changes in many organs due to both a direct toxic effect and a possible immunogenetic susceptibility to systemic sclerosis. Avoiding the exposure does not result in clinical improvement. Raynaud's phenomenon is the first symptom in up to 70% of patients with systemic sclerosis. In individuals with Raynaud's phenomenon a complete physical examination should be carried out, as well as a nailfold capillaroscopy and an autoimmune panel including anticentromer and anti-Sc1 70. 21409 [aut] This Finnish study evaluated 350 subjects with a mean age of 46 years. Coronary heart disease mortality was 17% lower in the northern-most area of Finland called Sami (formerly known as Lapp), compared to the reference area, which was six neighboring communities to the south. Those living in the low mortality area showed higher serum-lipid-adjusted vitamin E, albumin, selenium, cholesterol, and LDL cholesterol than those in the reference area. The HDL cholesterol:cholesterol ratio was lower in the Sami area than in the reference area. Serum vitamin E levels increased with the consumption of reindeer meet and serum selenium increased with fish consumption. The authors suggest that vitamin E, albumin, and selenium may play a role in the low mortality from coronary heart disease that is seen in the northern-most areas of Finland. Reindeer meat is rich in protein, essential fatty acids, vitamin E, and selenium, and is low in fat content. There was an increase in serum selenium with fish consumption, and an inverse association of serum selenium to cardiovascular mortality. An antioxidant-rich diet may retard the atherosclerotic vascular process and reduce the mortality from coronary heart disease, even with an unfavorable lipid profile. 21749 [car] This study measured glutathione and cysteine levels in 20 alcohol abusers and compared them to 20 subjects without liver cirrhosis. The glutathione levels were decreased while the cysteine levels were increased in all the patients. Two grams of SAME daily in 250 ml of 0.15 M NaCl for 15 days normalized the erythrocyte thiol alterations. The authors conclude that parenteral treatment with S-adenosyl-L-methionine affects the metabolism of sulfhydryl compounds in the erythrocytes of alcoholic patients. 21892 [gas, hep] In an in vitro study the effect garlic extract and one of its components S-allyl cysteine (SAC) was evaluated for its effect on hydrogen peroxide-induced injury using bovine pulmonary artery endothelial cells. Pretreatment with the age garlic extract (AGE) at 2 to 4 mg/ml and 4 mg/ml significantly reversed the loss of cell viability induced by 50 and 100 um of H202 AGE or SAC also exhibited a dose-dependent inhibition of both LDL release and lipid peroxidation induced by 50 um of H202. These results showed that both AGE and SAC can protect vascular endothelial cells from oxidant injury. The data suggests that these compounds may be useful for the retardation of aging process and for the prevention of cancer in atherosclerosis. 22243 [can, car] One hundred and seventy-four patients referred to the Department of Oral and Maxillofacial Surgery, Central Hospital, Karlstad, Sweden during 1987 and 1989 for lichenoid lesions were evaluated for the relationship to amalgam restorations. One hundred and fifty-nine of the patients were re-examined with the purpose of evaluating long term effect upon performed substitution therapy. Partial or total removal of amalgam had been recommended with specific criteria. The re-examination showed that 62 patients had performed partial and 69 patients total removal of amalgam fillings. Twenty- eight percent had not performed any substitution therapy. The results showed that 92% of the patients with lichenoid lesions only in contact with the amalgam fillings healed or improved clinically following removal of the amalgam. There was no statistical difference in healing between patients who only removed filling in contact and those who had removed all amalgam restorations. More than 60% of the buccal lichenoid lesions without contact with the amalgam had, at the time of referral, disappeared following amalgam substitution. The gingival lichenoid lesions did not respond to the substitution of amalgam to another material. Three of 17 patch-tested patients demonstrated hypersensitivity to mercury. All lichenoid lesions in these patients healed following substitution. Partial or total removal of amalgam fillings were also performed on 10 patients with completely negative patch tests. These patients showed a complete healing of their lichenoid lesions at re-examination. The authors conclude that dental amalgams play a role in the development of lichenoid reactions and should be removed when in clinical contact with the lichenoid lesion. Total removal of the amalgam may also be tried on other patients with long standing atrophic or erosive lesions where other forms of therapies have not had a beneficial result. 22642 [der, den] This study evaluated the pollution of operating-room air by narcotic gasses in 20 hospitals of Niedersachsen. In several cases the limits had been exceeded. Reasons for the increased levels included insufficient room ventilation, defective air-conditioning plants, technical defects and high gas emission due to special techniques in anesthesia such as bronchoscopy. The recommendations include keeping anesthetic gases as low as possible and to increase room ventilation while avoiding unnecessary emissions. 21587 [env, sur] This study compared 1,768 women with breast cancer to 13,905 controls, most of whom were below 55 years of age. The relative risk of breast cancer for women who had ever used depot medroxyprogesterone was 1.1. There was no increased risk with the increasing duration of depot medroxyprogesterone use but the relative risk estimates were higher in certain subgroups of women. Women who had started using depot medroxyprogesterone within the previous 5 years were estimated to have a relative risk of 2.0. The increased risk of breast cancer seen in users could be due to enhanced detection of breast tumors in women using depot medroxyprogesterone or to the acceleration of the growth of pre-existing tumors. Women who had used depot medroxyprogesterone more than 5 years previously had no increased risk of breast cancer regardless of the duration of use. Depot medroxyprogesterone acetate has been now approved for marketing as a contraceptive agent in the United States even though there are still some unresolved issues regarding its relationship to the risk to breast cancer. 21962 [can] In a double-blind, placebo-controlled trial, acetyl-L-carnitine at 3 gm per day was given to 7 probable Alzheimer's disease patients compared to 5 placebo-treated probable Alzheimer's disease patients and 21 age-matched healthy controls over a 1- year period. When compared to placebo, the Alzheimer's disease patients consuming acetyl-L-carnitine showed significantly less deterioration in their Mini-Mental Status and Alzheimer's Disease Assessment Scale test scores. The decrease in the phosphomonoester levels were seen in both acetyl-l-carnitine group and the placebo Alzheimer's group and was normalized in the acetyl-l-carnitine group only. There was a similar normalization of high-energy phosphate levels seen in the acetyl-l-carnitine- treated group, but not in the placebo group. This is the first direct in vivo demonstration of a beneficial effect of a drug on both clinical and CNS neurochemical parameters in Alzheimer's disease. 21803 [neu] Sixty-seven patients greater than 70 years of age admitted to a hospital with acute conditions were followed until death or hospital discharge. Patients with serum albumin concentrations less than 35 g/L showed a lower triiodothyronine (T3), a higher reversed triiodothyronine (rT3) concentrations and a higher death rate. Prior weight loss of greater than 10% did not affect thyroid status but increased the mortality rate. Eleven patients were hypothermic at less than 36.5ø C and a higher mortality, lower total T3 concentration and a higher reversed T3 concentration than normothermic or hypothermic patients. Serum albumin, body weight and total T3 concentrations were higher in 51 survivors than in the 16 nonsurvivors. A continued weight loss and hypoalbuminemia at admission are highly prevalent in elderly subjects with acute disease and can influence their clinical outcome. Mild hypothermia is a good predictor of death. Hypoalbuminemia and hypothermia were associated with low T3 and low rT3 values. 22373 [end, ger, hos] Five hundred and eighty-four healthy subjects of which 204 were women had homocysteine levels were evaluated along with 150 subjects with angiographically documented coronary artery disease. Plasma levels of vitamin B12, B6, pyridoxal phosphate, and folic acid were evaluated. Mean homocysteine levels were higher in the bottom quartiles for folate, vitamin B12, and pyridoxal phosphate. There was a significant correlation between homocysteine levels and folate and vitamin B12 levels. There is no significant correlation between plasma homocysteine levels another one of the classic risk factors. Control men had higher homocysteine levels than control women. Men and women with CAD had higher levels of homocysteine than controls. Men and women with coronary artery disease had similar homocysteine levels. Women and men with coronary artery disease had similar homocysteine levels, the 90th percentile of controls was 18.1% for men and 44.4% for women. There was significantly lower pyridoxal phosphate levels seen in subjects with coronary artery disease. No significant differences were seen for vitamin B12, folate, or B6. The multi-variate analysis revealed that elevated homocysteine is a risk factor for coronary artery disease in French Canadian men and women and that reduced levels of pyridoxal phosphate, folate, and vitamin B12 may contribute to the elevated homocysteine. The authors conclude that the treatment of elevated homocysteine levels on cardiovascular mortality and morbidity must be assessed. The mechanism by which homocysteine induces vascular damage is for the most part unknown. Homocysteine may have an adverse effect on endothelial cell function and may damage endothelial cells. Homocysteine may have an adverse effect on normal prothrombolytic and anticoagulant activities of endothelial cells. 22979 [car] Sixty-four children between 1 month and 6 years of age received 1 gm per kg activated charcoal combined with a 6% solution of magnesium citrate 0 ml/kg, 4 ml/kg, 6 ml/kg or 8 ml/kg. Median times to first charcoal stool were 19.5 hours, 13 hours, 14 hours and 12 hours respectively from 0 to 8 ml per kg. The authors conclude that magnesium citrate reduces gastrointestinal transit time of activated charcoal stools when administered to children who receive activated charcoal for a toxic ingestion. The clinical value of this reduction needs further study. 21864 [tox] This study did a prospective evaluation of over 85,000 women, 34 to 59 years of age without a history of heart disease or cancer. The relative risk of death in drinkers as compared to known drinkers was .83 for women who consumed 1.5 to 4.9 gm of alcohol per day, .88 for those who consumed 5.0 to 29.9 gm per day and 1.19 for those who consumed 30 gm or more per day after adjustment for other predictors of mortality. Light to moderate drinking 1.5 to 29.9 gm per day was associated with a decreased risk of death from cardiovascular disease. Heavier drinking was associated with an increased risk of deaths from other causes, in particular breast and cirrhosis. The beneficial of light to moderate drinking was most apparent in women with risk factors for coronary heart disease and for those 50 years of age or older. Beneficial effect of light to moderate alcohol consumption in reducing mortality appears to be largely confined to women at a greater risk for coronary artery disease. 22361 [age, car] This is a review article on the role of nutrition and incurable diseases. This article reviews some unproven dietary products to improve immune function and the role of nutritional support in palliative care. The use of mega-vitamin and mineral supplementation, which has not been proven in incurable diseases such as HIV infection, is quite popular. It is noted that in AIDS patients a daily multi-vitamin and mineral along with beta-carotene may be of benefit. Beta-carotene in doses of 60 to 180 mg showed a significant increase in CD4 (helper cells) in the 180 mg dosage, whereas there was a small increase in the 60 mg doses of natural killer cells. Reducing levels of linoleic acid and increasing eicosapentaenoic acid in animal models have inhibited the cytokine- mediated effects of endotoxin and suppressed acute phase protein concentrations. Though there is some suggestive evidence that glutamine and arginine need to be increased during stress and infection, the data for dietary lipids and amino acids in HIV infection are not strong enough to make recommendations. Among HIV þfad dietsþ, those rich in whole grains, fruits and vegetables with little or no meat or sugar are very popular. However, these diets are not energy dense; they should be discouraged on the basis that they may promote weight loss and enhance the progression to death. Another popular self-care treatment is the anticandida diet. The restriction of all carbohydrate-rich and yeast-containing foods makes this, as well, a low-energy-density diet. The use of live yogurt should not be recommended; it may possibly contain harmful bacteria. The author cautions about the use of Chinese herbs which may be expensive and have some toxicity associated with them. A painful mouth or throat from candidiasis, aphthous ulcers, side effects of drug therapy, palliative radiotherapy or prolonged malnutrition may require the reduction of all acidic foods and drinks. Many cancer patients have altered sense of taste which needs to be taken into account. Adequate fluid intake is important, and the use fiber encouraged. Bran, a rich source of insoluble fiber, should be avoided. Bananas and porridge may be used as alternative sources of fiber to peas and beans, which cause flatulence. Diarrhea can occur from malabsorption of lipids and can be supported with dietary supplements low in fat. Occasionally, a lactose-free diet or manipulation of dietary fiber can help to eliminate diarrhea symptoms. Aggressive feeding to maintain calories and body weight is important in both cancer and AIDS patients. 21614 [inf, nut] Sixty patients with a history of chronic epicondylalgia with typical pain for at least 3 months received 50 mg of glycosaminoglycan polysulfate injections or a placebo once a week for 5 weeks. The difference in the reduction of painscore ranging between 11.1 percentage units at the half year follow-up and 20.9 percentage units 2 weeks after the treatment period is good. The number of treatment failures in the glycosaminoglycan treated group at the 6 week follow-up was only 13% compared to 40% in the placebo treated group. At the end of the half year follow-up 5 of those who received glycosaminoglycan had experienced a recurrence of their symptoms. The recurrence rate is smaller than most of those reported in control studies with corticosteroids. In the glycosaminoglycan treated group 13 patients noted some local pain after some injections, 2 cases combined with local hematomas, compared with 5 cases of local pain in the placebo group. The results confirmed previous good results of glycosaminoglycan polysulfate injection therapy in subchronic and chronic peritendinitis. Glycosaminoglycan polysulfate injection therapy has a good pain relieving effect in chronic lateral epicondylalgia though there is frequently some transient but local pain at the injection site. The injections were given as infiltrations over an area of 2 cm2 under the ante-brachial fascia at the origin of the musculus extensor carpi radialis brevis. Subperiosteal injections were avoided. The patients were given paracetamole for analgesia. All the patients were asked to avoid the activities causing pain in the elbow until after 6 weeks assessment. After this period they were given a standard set of stretch and strength exercises. 22693 [exe] Osteoarthritis is the most common form of arthritis and affects more than 40 million Americans. It is characterized by joint degeneration, loss of cartilage and alterations of subchondral bone. There is a 35% incidence in the knees as early as age 30. Its incidence increases dramatically with age, affecting 80% of persons over the age of 50. As soon as possible, nonsteroidal antiinflammatories should be reduced, not only because of their gastrointestinal side effects, but also for their ability to inhibit collagen matrix synthesis and the acceleration of cartilage destruction, which may aggravate the osteoarthritic condition. Elimination of the genus Solanaceae (the night shade family of plants) from the diet may also produce benefit. This includes tomatoes, potatoes, egg plant, peppers and tobacco. It is suggested that these alkaloids inhibit normal collagen repair in the joints or promote inflammatory degeneration. Niacinamide at a dose between 900 and 4000 mg per day in divided doses has been shown to be of benefit, but liver damage and glucose intolerance are possible side effects of this treatment. Methionine is a sulfur-containing amino acid and is important in the maintenance of cartilage, especially proteoglycans and glycosaminoglycans. Injectable glycosaminoglycans polysulfate and activated acid-pepsin-digested calf tracheal cartilage, as well as other glycosaminoglycans, have yielded positive results. Glucosamine sulfate is a naturally-occurring substance found in joint structures which stimulates cartilage regeneration, protects against joint destruction, and alleviates the symptoms of osteoarthritis. Glucosamine sulfate is not an analgesic and takes several weeks before a symptomatic relief can be obtained. Vitamin E at 600 mg/d has shown benefit, possibly due to its membrane-stabilizing effect; this could also be due to its ability to inhibit the activities of the lysosomal enzymes and stimulate increased deposition of proteoglycan. Vitamin C between 1,000 and 3,000 mg a day can affect collagen synthesis and repair. In double-blind studies, pulse electromagnetic fields were shown to be of benefit. Also, exercise therapy is of extreme importance. Yucca at 2 to 4 gm 3 times daily is recommended. In a double blind study, the saponin extract of Yucca showed a positive therapeutic benefit. Cherries, Hawthorn berries and blueberries are rich sources of anthocyanidins and proanthocyanidins. These compounds are beneficial in enhancing collagen matrix integrity and structure. Elimination of all refined carbohydrates is recommended. If one is taking nonsteroidal antiinflammatory agents, the consumption of de Glycyrrhiza glabra or Robert's formula is recommended to protect the intestinal tract from the damaging effects of the NSAIDs. An unrefined diet is recommended. 21872 [ort] In culturing organisms that were recovered from the hands of more than 2,000 surgical intensive care unit personnel, up to 35% of the nurses and 27% of the physicians were carrying the candida species. The overall hand carriage rate among the health care workers was 33% in the surgical intensive care unit and 24% in the neonatal intensive care unit. There was considerable variation between the 6 university hospitals studied. As an example, hand carriage rates in the neonatal intensive care units ranged from 38.3% at Columbia- Presbyterian Medical Center in New York to 7.6% at the University of Iowa Medical Center in Iowa City. Physicians in the Iowa hospital had a 3% rate compared to more than 30% at Columbia- Presbyterian Medical Center. The most common candida species found on the health workers hands was Candida parapsilosis. The next most common was Candida albicans followed by Candida lusitaniae. 21376 [inf] In a randomized controlled trial vitamin A supplementation in 1,455 children between 6 and 59 months living in rural Northern Ghana were given 4 monthly oral doses of either 60 mg 200,000 I.U. of retinol or 30 mg for children between 6 and 11 months of age or 100,000 I.U. of retinyl palmitate plus 40 I.U. of vitamin E or placebo. The trial ran over 1 year. There was a tendency for vitamin A supplemented children but not placebo children to have elevated acute phase proteins in association with vomiting or severe diarrhea. The unsupplemented children failed to mount an acute phase response which may have contributed to their increased morbidity from gastrointestinal symptoms. 22972 [inf] This article reviews the combination role of 5-fluorouracil (5- FU) and folinic acid as therapies for colon cancer. The authors feel that a recent group of articles stating that the combination of 5-FU and folinic acid being dangerous is not correct. Careful analysis shows that the combination of 5-FU and folinic acid should be considered a standard therapy for patients with metastatic colorectal cancer. 5-FU plus folinic acid is associated with a higher therapeutic index compared to 5-FU alone. This combination leads to a better tumor control and relief of tumor related symptoms. The authors conclude that in the hands of an experienced physician 5-FU plus folinic acid is a safe treatment and not more toxic than 5-FU alone if dose modification guidelines are followed strictly. 22595 [can] Prudential is the largest supplier of health insurance and the largest owner of for-profit health maintenance organizations in the United States. It owns a big share of 5 of the 6 largest tobacco companies. At the beginning of 1995 Prudential owned over 12 million of R.J.R. Nabisco stock; 100 million of Phillip Morris; almost 97 million of stock in Loes (maker of Lorillard, Heritage, Kent and Newport); over 36 million of American Brands' which makes (Lucky Strike, Carlton and Benson & Hedges cigarettes among others); 44,000 of stock in Brooke Group which owns Laggett. Prudential's tobacco investments amount to at least 248 million. It could not be ascertained what their share was in the other top cigarette producer, British-based Brown and Williamson, which does not file a stock ownership report with the U.S. Securities and Exchange Commission. Even though Prudential has large investments in the tobacco industry, this is not uncommon among insurance companies. Traveler's Insurance Company held over 51 million in American Brands' stock, and 37 million in R.J. Nabisco. Met-Life, which recently merged with Traveler's to form the second largest health insurer, had over 15 million invested in RJR Nabisco. Signa, another insurance giant had invested over 18 million in American Brands' and 57 million in Phillip Morris. William H. Donaldson serves on the boards of Aetna and Phillip Morris. The investment bankers at Kohlberg Kravis Roberts, are the principal owners of R.J.R. Nabisco. R.J.R. Nabisco tried to add California's For-Profit Blue Cross Plan to their portfolio but were outbid. Why did the United States largest health insurers and HMO owners so heavily invest into tobacco? I think the cynical view is that this is a win-win strategy, much like the combination veterinarian/taxidermist who wins either way. From nonsmokers, insurance firms collect premiums and pay few claims. From smokers they collect even higher premiums while profiting from the habit that kills. The author suspects that Prudential's tobacco investment's strategy is more amoral than immoral. Health insurers and HMOs have billions to invest and tobacco, despite its recent bad press, is a good investment. Each day 1,000 U.S. smokers die from their addiction, but the industry recruits 1,000 replacements daily largely by promoting cigarettes to children and to people in the third world. The U.S.A. is progressing towards the world's first corporate-run for profit health care system. The government funded Medicare and Medicaid programs are being subcontracted For- Profit HMO's. Blue Cross plans, formerly not for profit, are selling themselves to investors. One similar firm owns 1/4 of Florida's hospitals and several university medical centers. The large drug firms have established disease management subsidiaries to subcontract HMOs for the care of high-cost chronic disease such as depression and diabetes. Another company bought a half interest in a chain of cancer clinics. It is noted that corporate executives are employed by shareholders not patients. Ultimately the laws of market demand allegiance to profit over health. That will give the incentive for corporate officers to maximize shareholder returns. 22815 [med] This article reviews the role of zinc in the form of an acetate salt and molybdenum in the form of ammonium tetrathiomolybdate in the treatment of Wilson's disease. Zinc can block copper absorption in the intestines by inducing intestinal cell metallothionein and is beneficial for maintenance therapy, treatment of presymptomatic patients from the beginning and the treatment of pregnant patients. Tetrathiomolybdate which complexes copper in a tripartite complex with protein is used for the initial treatment of neurologically presented patients. The dose of zinc is 50 mg of elemental zinc 3 times daily. The author notes that they have now over 100 patients on treatment with zinc on maintenance therapy. The longest treatment of these patients has been treated for greater than 12 years. There was a group of 40 patients who had been treated for greater than 5 years with zinc as their sole anti-copper agent. These patients have done well clinically with no new signs of Wilson's disease. Penicillamine has been used initially for the treatment of patients presenting with neurologic disorders in Wilson's disease. The mechanism is believed to be the immobilization of hepatic copper and subsequent elevation of brain copper or redistribution of copper within the brain which increases its toxicity. Many decades ago it was discovered in Australia and New Zealand that ruminants being on certain pasture developed a syndrome later found to be a copper deficiency. The soil pastures were found to be very high in molybdenum. Molybdenum administered in high doses to the ruminants produced copper deficiency. This supplementation of molybdenum to other mammals such as rats produced little effect. Later it was discovered within the rumen because of high sulfide metabolisms that molybdenum was being converted to thiomolybdate compounds. When these were administered to rats they were very effective anti- copper agents. Tetrathiomolybdate complexes with copper and protein in a tripartite complex. Such complexes of copper cannot be absorbed and cannot be taken by the cells. The molybdenum complex allows for patients to be immediately put into negative copper balance. The tetrathiomolybdate is given between meals in 3 doses to obtain blood absorption. The absorbed tetrathiomolybdate rapidly complexes available copper with albumin and the complex copper is not available for cellular uptake. It is therefore rendered nontoxic. If we give 20 mg of molybdenum 3 times a day with meals and an escalating dose between meals we have complexed all of the nonceruloplasmin plasma copper. The author's experience notes that between meal doses required to reach a state of equilibrium between molybdenum and copper is between 20 and 60 mg 3 times a day. Generally, with relatively rapid dose escalation this is able to be achieved within 3 to 9 days. The authors treat the patients for up to 8 weeks with this regimen of tetrathiomolybdate and then switched to maintenance therapy. Zinc is used in transition and the 2 drugs interact favorably during a 2 week transition period. The authors now have treated 17 patients with tetrathiomolybdate who presented with neurologic or psychiatric disease with complete success. There was no loss of function during the treatment period and most patients recover well over the 6 to 12 months. The author believes that tetrathiomolybdate is an exciting new therapy for the treatment of patients presenting initially with neurological disease. The optimal therapy for treating patients who present with liver disease is not yet clear. Patients who present with liver disease are given a combination of the chelator trien and zinc. It is noted that tetrathiomolybdate is used effectively as an intravenous therapy in copper poisoning to sheep. 22399 [met, tox] This is a response by Dr. Charles A. Crenshaw, M.D. on JAMA's review of his book by Dennis L. Breo. The book is entitled J.F.K. Conspiracy of Silence. In this letter Dr. Crenshaw states that he stands by his observations some 31 years ago in Parkland's Emergency Room that there was a gunshot wound from the front and that the throat wound was an entrance wound. The wound in the rear of the head was an exit wound as he had reported. He noted that JAMA did not print his 6,800 word article in rebuttal to the JAMA's 11,000 word article. The original article that JAMA refused to publish is scheduled to be published in 1995 by Open Archives Press, of which James Fetzer is an editor. His paper will be presented along with others submitted by the critics of the JAMA's coverage of the J.F.K. assassination. Dennis L. Breo's reply follows this article on page 1633. 22463 [tra] This study evaluated 50 pregnant patients with subnormal B12 levels between 45-109 pg/ml and compared them to 25 pregnant controls who had serum B12 levels between 208-508 pg/ml. In the subnormal group mean serum values for methylmalonic acid and total homocysteine were 445.4 nmol/L and 7.03 umol/L respectively which were not significantly different from the mean methylmalonic acid value of 440.5 nmol/L and homocysteine of 6.88 nmol/L in the controls. For the total group of patients neither serum methylmalonic acid nor serum homocysteine levels correlated with vitamin B12. One-third of the pregnant patients showed elevated serum methylmalonic acid levels independent of vitamin B12 status. Significant elevations of homocysteine were taken in only 2 patients with subnormal B12 and hematologic evidence of vitamin B12 deficiency. The authors conclude that the usual fall in serum B12 concentrations in pregnancy does not reflect B12 deficiency at the biochemical level. The authors state that to evaluate true vitamin B12 deficiency in pregnancy, serum levels of homocysteine level but not methylmalonic acid level is of value. The authors conclude that serum homocysteine levels in the absence of folate deficiency is a valid index of tissue vitamin B12 deficiency. 22217 [gyn, nut, obs] This study evaluated 25 dogs, 10 of which were supplemented with the EPA-ester at 100 mg/kg body weight per day for 8 weeks; 15 served as controls. After ingesting EPA for 8 weeks the ratio of eicosapentaenoic acid to arachidonic acid in platelet cell membranes was significantly increased. The EPA group had a reduction in the chemotactic response of neutrophils to leukotriene B4. Also in the EPA group the amount of 12-hydroxyeicosatetraenoic acid, one of the chemotactic products of arachidonic acid in the infarcted myocardium, was reduced to 40%. EPA treatment resulted in a significant reduction in the ultimate infarct size. In the EPA group the contractile function of the infarcted myocardium was preserved. Myeloperoxidase activity, which is a sign of infiltration of neutrophils into the infarcted myocardium, was less in the EPA group than in the controls. The authors conclude that dietary supplementation with eicosapentaenoic acid inhibits the ischemic myocardial damage through the inhibition of neutrophil infiltration in the damaged heart tissue. 21922 [car] One hundred and sixty women who had uncomplicated pregnancies were evaluated for altered maternal zinc metabolism and the association of low birth weight with raised maternal serum alpha-fetoprotein. Mothers with clinically normal pregnancies and normally formed infants but with raised maternal serum alpha-fetoprotein greater than the 90th percentile had lower than normal plasma zinc concentrations, raised leukocyte zinc and a disturbed zinc-albumin relationship. Due to shorter pregnancies and slower intrauterine growth, they delivered offspring with lower birth weight than did normal women with normal maternal serum alpha-fetoprotein. There appears to be a subgroup of mothers associated with low infant birth weight who have raised mean serum alpha-fetoprotein as well as altered zinc distribution. 21906 [obs] This study compared coronary risk factors in a randomly-selected group of 247 migrants from the Indian subcontinent of Punjabi living in West London and 117 of their siblings living in the Punjab in India. Those in the West London group had a greater body mass index, systolic blood pressure, serum cholesterol, apolipoprotein (b), lower HDL cholesterol and higher fasting glucose than siblings in Punjab. Insulin sensitivity was lower in men in the West London group than their counterparts in India. Indians in West London had lower beta cell function than those in Punjab. Serum lipoprotein (a) concentrations were similar in both areas. The lipoprotein levels, though, were higher than white European populations in the United Kingdom. The authors note that increases in serum cholesterol after migrating from India increased coronary risk by high serum lipoprotein (a) concentrations and greater insulin resistance. Such between- country comparisons are an important means of establishing coronary risk factors. In conclusion, body weight, serum cholesterol and blood pressure increased in Indians who migrate to the United Kingdom. They have higher lipoprotein (a) levels than indigenous populations and this is uneffected by migration. Their insulin resistance shows as an increase in blood glucose and an decrease in HDL cholesterol. On migration, they develop a coronary risk factor similar to that of the host community which unmasks the underlying genetic risk of coronary heart disease, resulting in high lipoprotein (a) levels and a predisposition towards insulin resistance. 21825 [car] This article reviews the metabolic effects of dioxin-type chemicals in pesticides and other xenobiotics. The most consistent toxic effects of dioxin-type chemicals are hyperlipidemia, body weight loss, anorexia, changes in carbohydrate metabolism and lipid peroxidation. Dioxin-type chemicals affect lipoprotein lipases, low-density lipoprotein receptors, glucose transporter proteins, vitamin C uptake and insulin secretion. It is suggested that 2,3, 7,8-tetrachlorodibenzo-p-dioxin (TCDD) directly acts with isolated cytosolic aryl-hydrocarbon (Ah) receptor under cell-free conditions even without the presence of the nucleus and is capable of activating key protein kinases that are involved in the growth factor signal-transduction pathway. The resulting activation of the primary-response transcription factors in the nucleus appears to play a role in coordinating vital cell program shifts which include lipid metabolism. 21944 [env, nut] This article reviews the literature regarding the role of smoking and cognitive performance. There has been great variability in results which may have to do with study design and also the different tasks required. While smoking had no negative effect upon performance for simple perceptual tasks, smoking was found to exert measurable negative effects upon performance for more complex information processing tasks. It is interesting to note that smokers are disproportionately involved in motor vehicle accidents, especially rear end collisions. In a computer driving simulator, smokers who had just smoked were involved in almost 3.5 times as many rear end collisions as nonsmokers. Smoking may have a positive impact on the performance of simple repetitive tasks, but may have a negative effect upon the performance of tasks with high demands upon problem solving skills requiring working memory. This negative effect is not overwhelming but under heavy tasks the deficit increases. It is clearly premature to conclude that smoking has positive benefits for behavior efficiency, facilitates storage, or helps concentration . . . or to discuss any beneficial effects of smoking on anything but the most routine and repetitive tasks. 21367 [neu] This article is a rebuttal to an article which stated that zinc therapy was not beneficial in burns. It is noted, from the author's experience, that supplementation with large doses of zinc during the first week after substantial thermal burns not only enhances zinc levels, but also enhances recovery by improving wound healing, resulting in a shortened hospital stay. 21503 [der, nut] This study compared 116 cases of bladder cancer to 232 controls for the risk of occupational exposure. There was a significantly elevated odds ratio for exposure to pyrolysis and combustion products. In women, there was an elevated odds ratio for ink exposure. 21594 [can] This is a editorial on the ability of soy to reduce cholesterol levels. Soy proteins have been repeatedly observed in carefully controlled animal models of hypercholesterolemia. Numerous human trials have attempted to produce these observations. Most of the studies have had too few participants and lacked the statistical power necessary to detect the effects of dietary intervention. In Anderson's review in the New England Journal of Medicine, 1995;333:276-282 a meta-analysis of 38 separate studies involving more than 740 participants, showed the consumption of soy protein rather than animal protein resulted in a significant reduction in serum concentrations of total cholesterol, low density lipoprotein cholesterol and triglycerides without significantly changing the concentration of HDL cholesterol. Soy protein had a greater effect when reducing total cholesterol and LDL cholesterol in subjects with higher initial serum cholesterol concentrations. The effective component in soy may be the soy protein itself. It may be due to the fact that the amino acid pattern in peptide structure as well as nonprotein compounds such as isoflavones and saponins. It may be that 1 or more components of soy modulate functional properties of the vascular endothelium in smooth muscle cells as well as macrophages and T cells that infiltrate evolving atheromatous lesions. The safety of consuming soy appears to be intact since some Asian populations typically consume 20 gm of soy protein daily in soy milk, tofu, and tempeh. There is a long history of safety. Soy protein is close to the quality of animal protein. Allergic reactions to soy protein are rare in adults although soy protein like cow's milk, eggs, and wheat proteins occasionally produce allergic responses in children. Soy products incorporated into a diverse and balanced diet have little effect on mineral status. There is ongoing research to find novel ways to incorporate soy protein into baked foods, drinks, soups, and entrees during 6 month feeding trials involving postmenopausal women with hypercholesterolemia. 22971 [car] This was a nationwide case-controlled study covering a region with 78% of all births in New Zealand between 1987 and 1990. Interviews were completed with the parents of 393 cases of infants who died with sudden infant death syndrome in the postneonatal age group and 1,592 controls. 26% of the SIDS deaths were explained by bed sharing among infants of smoking mothers and 3% by bed sharing among infants of nonsmoking mothers. The majority of SIDS deaths that are attributed to bed sharing occur among infants of smoking mothers. This data should not be interpreted to suggest that bed sharing where the mother is a nonsmoker is safe or protective against SIDS. The authors conclude that an extra 3% of sudden infant deaths could be saved by a general message for all infants not to bed share compared to messages targeted to the infants of smoking mothers. Current favorable attitudes towards infant bed sharing may jeopardize the acceptance of other cot death prevention messages if it is perceived that the evidence does not justify a general recommendation against this practice. 22675 [ped] Exercise should be the prescription for osteoarthritis. The goal is to use a lot fewer nonsteroidal antiinflammatory agents and a lot more exercise. The Arthritis Foundation states that physical therapy may be the most valuable treatment for the estimated 16 million people in the United States who have osteoarthritis. Physicians should prescribe a low impact exercise program involving keeping the joints flexible, preserving the strength of the muscles on which the joints depend for their stability and protecting diseased joints against further damaging stresses. Exercise also requires the patient to take charge of their therapy. It is noted that exercise is one of the prescriptions that doctors feel most uncomfortable writing. In a study of 110 elderly patients with osteoarthritis of the knee and/or hip fewer than 48% had received medical advice to exercise and very few had received enough exercise related teaching in Arthritis Care and Research, 1992;5:36-41. It is noted that the Arthritis Foundation has 70 chapters in the United States and sponsors a series of exercise programs. You can call the foundation at 1 (800) 283- 7800 to determine where to send your patients if you are a physician. Chapters have monthly classes. Those with osteoarthritis may benefit by doing exercise in the morning. Trying to get 10 repetitions is beneficial but if the pain persists they can go down to 5 repetitions. If they have no pain they should work towards 20 repetitions. One study of 102 patients with documented primary osteoarthritis of one or both knees showed that exercising patients decreased medication use when compared to nonexercising individuals. This was in the Annals of Internal Medicine, 1992;116:529-534. Reducing the dose of nonsteroidal anti-inflammatory agents reduces the level of risk to gastrointestinal side effects. One study showed that the rate of gastrointestinal bleeding was 52% in patients receiving 2 nonsteroidal anti-inflammatory agents and 23% of those receiving 1. High dose nonsteroidals have not been shown to change the course of the disease. It is not clear that the joint pain is due to synovitis. The general cost of nonsteroidal antiinflammatory agents in comparison with acetaminophen is generally greater with more significant side effects. It is reasonable to consider acetaminophen as a first line therapy in the symptomatic management of patients with osteoarthritis. Side effects of nonsteroidals include gastropathy, renal insufficiency and neurologic complications are the most common in elderly patients. The annual rate of hospitalizations for peptic ulcer disease among elderly patients taking antiinflammatory doses of nonsteroidal anti-inflammatory agents is nearly 7 in 100, about 4 times the rate for elderly not on nonsteroidals. Also 30% of hospitalizations and deaths related to peptic ulcer disease are attributed to nonsteroidal antiinflammatory drugs (Annals of Internal Medicine, 1991;114:257-263). The higher cost of nonsteroidal anti-inflammatory agents is also changing prescription practices. Managed care is changing around prescription practices where almost a decade ago nonsteroidals were the initial prescription for osteoarthritis in nearly 6 million physicians. 21896 [ort, rhe] This study evaluated 21 women who had experienced at least 3 vaginal candidiasis infections within the previous 12 months and 15 female control subjects. The authors found no difference in mean zinc concentrations of plasma and cervicovaginal secretions between the two groups. Zinc levels of plasma and cervical secretions had no correlation. These results do not confirm the previous hypothesis that zinc deficiency of the serum is a risk factor for recurrent vulvovaginitis. It is possible that the local zinc levels of the cervicovaginal secretions influence antifungal activity of third generation azole antimycotics. 21520 [gyn] Out of a total of 286 individuals, the total cumulative incidence of pressure ulcers was 12.9% or 37 after a median time of 9 days from admission to skin examination. The following characteristics were significantly associated with pressure ulcer development by univariate Kaplan-Meier Survival Analysis: age of 75 years or more, dry skin, nonblanchable erythema, previous ulcer history, immobility, fecal incontinence, depleted triceps skin fold, lymphopenia and decreased body weight. Risk ratios for predictors of pressure ulcer development after regression analysis included nonblanchable erythema at 7.52, lymphopenia at 4.86, immobility at 2.36, dry skin at 2.31 and decreased body weight at 2.18. The 3 week cumulative incidence of pressure ulcers with zero, 1, 2 or 3 or more of these characteristics was 0%, 11.4%, 39.6% and 67.9% respectively. These results suggest that nonblanchable erythema, lymphopenia, immobility, dry skin and decreased body weight are independent and significant risk factors for pressure ulcers in hospitalized patients whose activities are limited to a bed or chair. 21978 [der, hos] This study evaluated 100 patients of which 60 were female and 40 were male. Forty suffered migraine with aura and 60 from migraine without aura. The patients were evaluated in the interictal period. Thirty patients with aura and 48 migraine patients without aura were also assessed ictally. The migraine patients with and without aura in the interictal periods had a reduced mononuclear magnesium content compared to age-matched healthy controls. There was no difference observed between ictal and interictal periods in migraines with and without aura. This lower amount of magnesium in the mononuclear cells could be indirectly related to a reduced brain magnesium concentration which has been shown in the course of migraine. 21556 [neu] This study evaluated 51 patients younger than 65 years and 46 patients 65 years of age or older who were referred for a refeeding after having lost at least 20% of their body weight and at least 10% in 3 months. Total energy intakes were 288% and 282% of the resting energy expenditure in groups 1 and 2, respectively, and the duration of cyclic enteral nutrition was a mean of 27 days in both groups. Tolerance was generally good. In both groups, 7 nutritional parameters and the global nutritional deficiency improved significantly. Body weight, serum albumin, serum prealbumin, serum transferrin, 24-hour urinary creatinine and the global nutritional deficiency improved to a greater extent in younger patients. Cyclic enteral nutrition appears to be well tolerated and an effective means of treating under nutrition in older, malnourished ambulatory patients even though the response to this approach is somewhat less than in younger patients. 21827 [nut] In looking at the documents from the Brown & Williamson Tobacco Corporation, the British American Tobacco Company and other tobacco interests, the documents showed a sophisticated legal and public strategy to avoid liability for the disease induced by tobacco use. The documents showed that lawyers steered scientists away from particular research avenues. It is noted if the company had been unconvinced by the causation and addiction hypothesis, than it should have had no concern that new research would provide ammunition for the enemy. The document shows that the Brown & Williamson Tobacco Company and the British American Tobacco Company knew more than 30 years ago that nicotine is addictive and that tobacco is biologically active in regards to carcinogenesis. 22885 [can, med] Sources of lead exposure to children include lead based paint, lead contaminated soil, house dust, food and drinking water, leaded gasoline, parental occupations and hobbies, industrial emissions, lead-glazed ceramicware, lead-solder cans and some traditional medicines and cosmetics. Ingestion is a primary route of exposure to children. A survey of 43 directors of medical school affiliated lead clinics located in 18 cities concluded that: 1. There is a wide range of blood lead levels for which chelation therapy is recommended. 2. The majority of children with blood lead levels of 1.21 umol/l to 2.17 umol/l (25 ug/dl to 45 ug/dl) with negative CaEDTA provocation tests do not receive chelation therapy. Oral chelating agents are used in the minority of clinics. There is no common approach for the treatment of lead toxicity as present. In the majority of pediatric centers current management of blood lead elevation did not appear to reflect the new information regarding the effects and treatment of lead poisoning. It is noted that meso- 2,3-dimercaptosuccinic acid (succimer) is a promising new oral treatment for lead poisoning. Succimer is a chemical analog of British antilewisite that forms water soluble complexes with lead that are excreted by the kidneys. Succimer is approved only for the treatment of children with blood lead levels greater than 2.17 umol/l (45 ug/dl). Succimer is equally effective as lowering lead levels in children with levels less than 2.17 umol/l (45 ug/dl). The drug has several advantages in that it is orally administered; it is well tolerated with infrequent side effects and it is a relatively specific chelating agent for lead producing less undesired excretion of zinc, copper, iron and calcium EDTA. Health and nutritional counseling is probably the most cost effective means to approach children with exposures less than .97 umol/l (20 ug/dl). Children with lead levels greater than .97 umol/L (20 ug/dL) should receive more involved intervention. Intervention should include reducing the child's body burden and absorption of lead, chelation therapy, treating calcium and iron deficiency and identifying and removing sources of lead. 22187 [env, tox] Elevated homocysteine levels occur frequently in end stage renal disease. This study evaluated total fasting homocysteine, plasma levels of folic acid, pyridoxal 5'-phosphate, plasma vitamin B12 levels, serine, total cholesterol and HDL cholesterol, glucose, creatinine in 24 end stage renal disease patients on dialysis compared to 24 age-matched controls. Mean plasma homocysteine levels were considerably higher in end stage renal disease patients versus controls. End stage renal disease patients were 3 times more likely to have elevated homocysteine levels. These elevated homocysteine levels persisted in end stage renal disease patients despite normal to super normal B vitamin status. Plasma serine levels below the 10th percentile of the control distribution were found in 75% of the end stage renal disease patients. Oral L-serine was given in 3 or 4.5 gm tablets taken twice daily for a total of 3 gm in 1 patient and 4 gm in 3 patients for 7 days and then stopped. This resulted in a 37% increase in plasma serine levels but no effect on plasma homocysteine in 4 end stage renal disease patients with supernormal levels of plasma serine and hyperhomocysteinemia. It is possible that reducing hyperhomocysteinemia might reduce cardiovascular consequences of end stage renal disease. Supplementation trials need to be done to confirm this. 22221 [car, nep] In a random, computer generated sample of 70 family physicians and general practitioners who were selected from 386 eligible participants in the Eastern third of Iowa 53 of these individuals were interviewed in-depth and asked to describe their most memorable errors and the perceived causes. There was a mean report of 8 different causes for each case in which an error was made. In 47% of the cases the patient died following the error whereas in 26% of the cases there was no adverse outcome. Only 4 of 53 errors lead to malpractice suits and none were addressed by peer review organizations. Ten percent of the seventy physicians who were invited to participate could not recall having made any errors. Family physicians attributed their most memorable errors to 34 different causes which fit into the following categories: Physician stressors, process of care factors, patient related factors and physician characteristics. Family physicians attribute their most memorable mistakes to a wide range of causes but most commonly hurrying distraction, lack of knowledge, premature closure of a diagnostic process and inadequate aggressive patient management. It is hoped that physicians who understand the causes of these common errors may be better prepared to prevent them. 22147 [med] This article reviews the role of nutritional support in critically ill patients. Medium-chain fatty acids, branched-chain amino acids and glutamine have shown benefit and should be of common use in the future in critically ill patients. Short chain fatty acids need further investigation. Vitamins E, C, arginine, glutamine and omega-3 fatty acids show promise as pharmacologic agents that can manipulate the stress response. More research needs to be done on nucleotides. Medium-chain triglycerides have helped maintain nitrogen balance. The branched-chain amino acids isoleucine, leucine and valine appear to have benefits during maximal stress; a 45% enrichment is considered optimal. Glutamine is important for nucleotide and protein synthesis and is an important substrate for rapidly dividing cells, including those of the gastrointestinal tract, pancreas, pulmonary alveoli and white blood cells. Oxidation of glutamine via the Krebs cycle results in adenosine triphosphate. Divided doses of 6 to 30 gm per day have been recommended for oral use, and up to .57 g/kg/day for intravenous treatment. Short chain fatty acids are an alternate fuel which are produced in the colon by fermentation of dietary carbohydrates and fiber polysaccharides and are absorbed readily through the colonocyte brush border. Short chain fatty acids are not available as of yet via intravenous infusion. Supplementation of 25 to 37.5 gm of albumin per day intravenously until serum albumin rises to 3 gm% in stressed patients may be of benefit. Supplementation of enteral and parenteral solutions of 50 to 60 I.U. of vitamin E/day and 500 mg of vitamin C/day may also help the stress response. Fifteen to thirty gm of arginine per day may help the stressed patient as well. Dietary nucleotides are important for cell-mediated immunity and helper/inducer T-lymphocyte function. RNA has been found to be a source of nucleotides. Omega-3 fatty acids can help reduce the production of interleukin I, tumor necrosis factor and interleukin VI. In burn models, omega-3 fatty acids have been shown to be of benefit. In one study, a group patients undergoing abdominal surgery for gastrointestinal malignancy consumed either Impact or Osmolite HN. The Impact product contained 1.68 gm of omega-3 fatty acids, 14 gm of arginine, 11.8 gm of glutamic acid and 1.2 gm of ribonucleic acid per 1,000 kcal. The Osmolite HN product contained only 1.73 gm of arginine and 8.7 gm of glutamic acid per 1,000 kcal with no omega-3 fatty acids or ribonucleic acid. The Impact group had fewer wound complications (11% versus 37%), improved lymphocyte mitogenesis and a shortened hospital stay of 15.8 versus 20.2 days. The integration of nutritional therapy hopefully will improve the outcome of critical care patients. As more nutrients become available for intravenous administration, the safety and efficacy of intravenous feedings will likely improve patient outcomes. 21355 [cri, nut] This study evaluated 4 population based cohorts in nationwide cancer registries in which there were 34,641 individuals with non-Hodgkin's lymphoma, 17,400 with chronic lymphocytic leukemia, 34,989 with malignant melanoma, 25,980 with squamous cell cancer. A total of 562,085 person-years were accrued for the study. The relative risk for developing squamous cell cancer was 5.5 among patients with non-Hodgkin's lymphoma and 8.6 among patients with chronic lymphocytic leukemia. The relative risk remained high over 15 years of follow-up. The relative risk for malignant melanoma were 2.4 for past patients with non-Hodgkin's lymphoma and 3.1 for patients with chronic lymphocytic leukemia. After squamous cell skin cancer had been diagnosed, there was a 2-fold increased risk for non-Hodgkin's lymphoma and chronic lymphocytic leukemia. The authors conclude that the occurrence of non- Hodgkin's lymphoma and skin cancer are strongly associated. This supports the hypothesis that "secular" increase in ultraviolet light exposure may be a contributing factor to the increasing incidence of non-Hodgkin's lymphoma in recent decades. 22656 [can, der] In a double-blind, placebo-controlled trial, 30 mild- to moderately-demented patients with probable Alzheimer's disease were randomly assigned to receive either acetyl levocarnitine hydrochloride at 2.5 gm per day for 3 months followed by 3 gm per day for 3 months, or a placebo. After 6 months, the treated group showed significantly less deterioration in timed cancellation tasks and Digit Span, and a trend towards less deterioration in time verbal fluency task. A subgroup with the lowest baseline scores receiving acetyl levocarnitine had significantly less deterioration in verbal memory test and a significant increase in cerebrospinal fluid acetyl levocarnitine levels compared with those receiving a placebo. This data suggests that acetyl levocarnitine may retard the deterioration in some cognitive areas in patients with Alzheimer's disease. 22824 [neu] This study evaluated almost 14,000 residents of a retirement community for a 9 year follow-up period. There were 65 incident cases of pancreatic cancer discovered. Higher intakes of vegetables, fruit, beta-carotene and vitamin C were associated with a reduced risk of pancreatic cancer although none were statistically significant. The risk of pancreatic cancer decreased with increasing tea consumption but was unrelated to coffee. There was no stronger consistent association seen between either smoking or alcohol consumption and the risk of pancreatic cancer. There was a consistent and significant risk following cholecystectomy of pancreatic cancer. It is noted that the findings for the association between pancreatic cancer and cholecystectomy have been inconsistent. Cholecystokinin is a peptide hormone produced by the intestinal mucosa that stimulates the contraction of the gallbladder and pancreatic enzyme secretion. Cholecystokinin has been shown to be important in experimental pancreatic carcinogenesis. Endogenous cholecystokinin appears to be responsible for pancreatic growth following pancreatic juice diversion. Cholecystectomy may result in breakdown of the feedback controlling the release of cholecystokinin, and may precipitate an increased risk of pancreatic cancer by the trophic effect of cholecystokinin on the pancreatic acinar cells. 21608 [can] In evaluating over 14,900 participants in the Physiciansþ Health Study for the relationship of myocardial infarction and fish oil, a lack of association between fish oil levels and the incidence of myocardial infarction was shown. The authors concluded that fish oil does not reduce the risk of myocardial infarction. The effect of very high doses was not evaluated. 21756 [car, nut] This discussion suggests that the increased risk associated with abdominal obesity is mediated by increased levels and fluxes of free fatty acids. The article reviews strategies for reducing free fatty acid levels and or flux which include the very low fat, low glycemic index diet which promotes insulin sensitivity via exercise, chromium supplementation, soluble fiber or drugs, antilipolytic agents, the stimulation of hepatic lipid oxidation with hydroxycitrate, carnitine and possibly omega-3 fatty acids. The authors note that when the treatment of obesity appears to be refractory it may be possible to reduce the cardiovascular risk associated with obesity by modulating free fatty acids. 22905 [car, met, obs] This is an extensive review article on the role of the management pharmacologically and lifestyle wise of hypercholesterolemia. Risk factors to coronary artery disease include age, maleness, lack of estrogen replacement therapy, cigarette smoking, diabetes mellitus, family history of heart attack, low HDL cholesterol less than 35 mg/dl and high blood pressure. A cholesterol lowering diet is recommended using the Step I and Step II outlines from the National Cholesterol Education Program which have carbohydrates of greater than 55%, cholesterol under 200 or 300 mg per dl, protein 15%, total fat 30% with the Step II Diet being more strict on the percent of saturated fat being less than 7% and polyunsaturated fats less than 10%. Among the medications reviewed nicotinic acid is noted to reduce the synthesis of LDL cholesterol by reducing the hepatic synthesis of VLDL cholesterol, increases the synthesis of HDL cholesterol, inhibits lipolysis in the adipose tissue and increases lipase activity. Within 3 to 5 weeks of the initiation of nicotinic acid therapy the LDL cholesterol and triglyceride levels decreased and the HDL cholesterol increases. Nicotinic acid therapy should be considered in patients with elevated LDL cholesterol or in patients with elevated serum cholesterol and triglycerides. The use of nicotinic acid is limited by its side effects which mainly are cutaneous flushing and pruritus and itching. This frequently diminishes after several weeks of therapy. Flushing can be lessened by slowly increasing the dosage or by having the patient take an aspirin 1 hour before each dose. Other side effects include nausea, diarrhea, abdominal pain and elevated liver function. Sustain release preparations are more hepatotoxic. Occasionally nicotinic acid can activate an ulcer, cause arrhythmias, hepatitis, aggravation of diabetes mellitus and elevate uric acid. Nicotinic acid is the cheapest of the cholesterol lowering agents ranging from $3.00 to $29.00 per month. 22198 [car] Fourteen postmenopausal females on hormone replacement therapy had significantly lower concentrations with serum zinc compared with 11 untreated controls and 13 premenopausal females. Impaired intestinal absorption was documented by low urinary zinc in most of the hormone replacement therapy subjects, but 2 had elevated values. Serum albumin concentrations of the hormone replacement group were slightly lower than those of other groups. This might be responsible for the reduction of serum zinc. This study showed that long-term use of hormone replacement therapy produces a reduction in serum zinc concentration. This is partly due to changes in circulating albumin levels, but the hormone replacement may also adversely effect intestinal absorption of zinc. The reduction of serum zinc levels was approximately 2.5 umol/l in the postmenopausal women who received the hormone replacement therapy. 21799 [gyn] This study evaluated women with premature ovarian failure. Pregnancy occurred in these individuals in the absence of ovarian function. Concentrations of testosterone and androstenedione were very low if not lower than nonpregnant women. These concentrations were significantly increased in normal pregnancies and were even further increased in human menopausal gonadotrophin-treated cycles. This research shows that the ovary is a contributor to the circulating concentrations of testosterone and androstenedione starting within the cycle of conception. 22453 [rep] This study evaluated 184 males who were undergoing initial screening for infertility. More than 50% and 70% of the subjects had normal sperm density and motility, respectively. Mean blood lead levels and seminal plasma lead levels were 7.09 ug/dL and 12.98 ug/L respectively. The mean concentrations of cadmium in the blood and in the seminal plasma were 0.95 ug/L and 0.58 ug/L, respectively. Blood cadmium and cigarette-years were significantly and inversely correlated with sperm density. The authors conclude that cigarette smoking appears to affect sperm density, especially in heavy smokers. Cadmium in the cigarettes may be a possible causative agent for low sperm density in smokers. 21742 [env, rep] Mercury vapor from dental amalgam has been demonstrated to exceed the sum of all other sources of mercury exposure. The effects of inorganic mercury exposure on cell function in the brain and intestinal bacteria has recently been examined. In a rat model the authors showed that ADP-ribosylation of tubulin and actin brain proteins is markedly inhibited. The ionic mercury can alter a neurochemical reaction involving the maintenance of neuromembrane structure. In a monkey model mercury from amalgam has been shown to enrich the intestinal flora with mercury resistant bacterial species which can result in resistant strains of bacteria to antibiotics. The authors conclude that from the 2 animal studies they have shown that small amounts of mercury similar to those seen in the tissues from exposure to amalgams can result in profound effects upon cell function. Also occupational exposure to mercury in dental personnel can effect reproductive function. The Dental Association maintains an viewpoint that dental amalgams are safe for human use because of their popularity over the last 150 years. The accumulating medical research continues to support the view that chronic mercury exposure from dental fillings may have important adverse health implications. 22232 [tox] Since the 1960s and 1970s the observation in the Greenland Eskimos of omega-3 fatty acids shifted research towards that group. The Seven Country Study showed an average saturated fat intake to be strongly related to 15 years' mortality from coronary heart disease. These results suggest that a highly saturated fat intake results in a higher mortality from coronary heart disease. In several studies there was no association found between the intake of different fatty acids and coronary heart disease. In the Western Electric Study there was a significant inverse association between polyunsaturated fatty acid intake and coronary heart disease. The studies of Dr. Dyerberg in the 1970s showed that the average intake of omega-3 polyunsaturated fatty acids was 2 to 3 times higher than the intake of omega-6 fatty acids. The diet of the Eskimos were characterized by 39% from fat with a low amount of saturated fat and a high polyunsaturated to saturated fat ratio. The intake of monounsaturated fats was also high. Compared to Danish mortality data only 3 cases of acute myocardial infarction were found when 40 cases were to be expected. The data was exciting in the Eskimos but it did not justify a conclusion in the causal relationship to ischemic heart disease. An analysis of the Zupthon Study from Holland showed that fish consumption at the start of the study was inversely related to mortality from coronary heart disease in the period 10 to 20 years later. Mortality from coronary heart disease is about 2 times lower among males eating at least 30 gm of fish per day compared with non-eaters. The dose response relationship was observed between 0 and 30 gm of fish per day. In 1957 the Western Electric Study evaluating 2,000 males in Chicago showed an inverse relationship found between fish consumption and coronary heart disease during 25 years of follow- up. This was also found in a Swedish study. Two other studies did not confirm the relationship with fish consumption. In the large American MRFIT Study dietary fish intake has been followed and omega-3 fatty acids have been reported to be inversely related to total mortality and mortality from ischemic heart disease. Epidemiologic data in Alaska showed the Eskimos have a substantially lower extent of atherosclerosis as compared to nonnative Alaskans. 22760 [car] Tryptophan and cataracts have been linked for some time. Total serum tryptophan levels are lower in fasting cataract patients than in comparable controls. Tryptamine has been shown to inhibit ATPAs activity in the toad but not in rabbit lenses. Several intermediates in the tryptophan catabolic pathway become reactive on oxygen exposure. Two mechanisms can be proposed for this. First, elevated levels of reactive compounds may act on the lens enzymes to rendered them less active. Another mode of interaction of the reactive oxygen species, not related to the first, is the direct covalent modification of structural proteins in the lens. The human cataract may have its origin in the relativity of metabolites which, under normal circumstances, are found to protect the lens itself from UV-induced photo damage. Hydrogen peroxide may be formed by auto-oxidation of its metabolites within the lens, rather than arising from external sources. This hypothesis can be tested by examining cataract lenses for the presence of adducts characteristic of modification by 3-hydroxykynurenine. 22992 [oph] In the 1920s before anticonvulsant medications were available high fat diets were used to control seizures in epileptic children. Clinical trials are now confirming that this does work "better than any other regimen" according to Dr. John M. Freeman, the director of the Pediatric Epilepsy Clinic at Children's Center in Baltimore, Maryland. He recommends this diet for children who don't respond to anticonvulsants. It is a stringent diet consisting of high fat, low protein, low carbohydrate foods. No drug company is promoting this regimen as they do conventional antiepileptics, so this therapy is not well known. It is estimated by some experts that this diet can lead to a reduction of seizures in 50 to 70%of the children, which few drugs can claim. According to Dr. Freeman the concern about the diet elevating cholesterol levels is not warranted. Dr. Freeman states, þAssume the diet is atherogenic. It is still better than poisoning a child's brain for 10 years.þ Giving a pill is much easier than putting a child on a strict diet. Patients initially should be hospitalized to ensure that the metabolic processes derived from the diet will be initiated. In 1 neurologist's experience, one third of the children who start the diet don't tolerate it. Side effects include diarrhea and dehydration. A sample diet for 2 days includes: Breakfast of scrambled eggs, butter, diluted cream, orange juice. Lunch: Lettuce leaf with mayonnaise, spaghetti, squash with butter and Parmesan cheese, orange diet soda mixed with whipped cream. Dinner: Asparagus with butter, chopped lettuce with mayonnaise, hot dog slices with ketchup and vanilla cream popsicle. Day 2, breakfast: Bacon, melon slices, scrambled eggs with butter and a vanilla cream shake. Lunch: Celery and cucumber sticks, tuna with mayonnaise and sugarless jello with whipped cream. Dinner: Chopped lettuce with mayonnaise, broiled chicken breasts and a cinnamon apple slice with butter topped with vanilla ice cream. The ratio of fats to protein and carbohydrates combined is 4:1 for children starting out on the diet; it can usually be lowered to 3:1 after the first year. The ketogenic diet allows children three fourths of the recommended daily allowances of calories for their ideal body weight. Even things like toothpaste need to be taken into consideration with regards to calories. Dr. John M. Freeman has written a book entitled, The Epilepsy Diet Treatment: An Introduction to the Ketogenic Diet, by Demos Publications 1994 of New York. 21550 [neu] Tannin in red wines appears to prevent a rebound platelet aggregating effect that is seen frequently after alcohol consumption. In a model of 144 rats fed water mixed with 6% alcohol from white wine, red wine or straight ethanol, there was a reduction in the blood's tendency to clot by about 70%. When the animals that consumed white wine and straight alcohol were taken off the diet their blood clotting tendency rose dramatically in the 14 hours after drinking, by 46% and 124% respectively. The rats fed the red wine did not suffer a rebound effect, and their platelet aggregation was still reduced by 59%. Tannins appear to be the agent that helps avoid the rebound effect. This benefit could also be from polyphenols and not tannins. Components of red wine can help reduce platelet activity but not make the patient a bleeder. 21705 [car, nut] Forty-seven normal healthy subjects and 27 patients with unstable angina were evaluated for adenosine diphosphate-induced platelet aggregation. The adenosine diphosphate concentration required for half the maximal aggregation was significantly lower in the stable angina patients compared with that for normal individuals. Platelet aggregation is a useful prognostic indicator for unstable angina. 22475 [car] Nine healthy individuals were supplemented with 316 mmol of magnesium per day for 30 days. Total magnesium levels did not change throughout the whole time of the experiment. Ionizable magnesium decreased during the first 10 days and bound magnesium tended to increase. Ionizable magnesium and not calcium was positively associated with parathyroid hormone. On day 0 calcium and ionized magnesium correlated with parathyroid levels. Both of these correlations vanished after magnesium supplementation. By keeping the levels of parathyroid hormone down, it ensures that supplemented magnesium enters the bone and is not liberated along with calcium by possibly increased parathyroid levels, triggered by high circulating magnesium concentrations. 22024 [nut] This study evaluated 548 males 40 years after their birth of which 253 had been exposed to diethylstilbestrol in utero compared to 241 who had not been exposed. Congenital malformations of the genitalia were reported 3 times as often by diethylstilbestrol exposed men as by sons of women in the placebo group. In the exposed group malformations were twice as often reported among those exposed to diethylstilbestrol before the 11th week of gestation as among those exposed later. Men with genital malformation were as fertile as other men. Diethylstilbestrol- exposed men had no impairment of fertility in any measure. Diethylstilbestrol-exposed men had no impairment of sexual function. The authors concluded that high levels of diethylstilbestrol did not lead to impairment of fertility or sexual function in adult men who had been exposed to the drug in utero. 22474 [rep] In a rat model induced glomerulonephritis in a study utilizing a diet that was normal in protein intake yet restricted in L- arginine. This resulted in decreased protein, decreased expression of TGF-B1, messenger RNA and TGF-B1 protein and decrease the production and deposition of matrix components. L-arginine, not D- arginine supplementation to low protein diets reversed this effect. This data suggests arginine is a key component in the beneficial effects of a low protein diet. 22843 [nep, nut] Dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) were formerly thought of as "weak androgens". DHEAS is generated in the liver from the parent adrenal steroid DHEA. It circulates in the blood of man and other primates in very large quantities. DHEA(S) concentrations peak at 20 years of age declining thereafter. By 60 years of age the level is 1/3rd or less of those than in young adults. Decreases of DHEA have been associated with age-related diseases such as ischemic heart disease, non-insulin-dependent diabetes and some form of cancer. In animal models DHEA supplementation has shown benefit in vascular stenosis in heart transplant patients, has had anticarcinogenic effects, has helped reduce weight in obese rats and also may effect the brain. Experimentally DHEA(S) enhances some form of memory and reduces aggression. In some studies DHEA(S) enhances some forms of memory and reduces aggression. DHEA(S) also has a powerful antiglucocorticoid action. Low DHEA(S) may accentuate the immunosuppressive effects of increased corticoids during stress and trauma. Increased cortisol can cause brain damage in animals. Low DHEA(S) in the aging brain may predispose it to damage or allow endogenous normal concentrations of cortisol to act as a neurotoxic agent. DHEA at 50 mg per day has been shown to produce blood levels of early adulthood. Two reports describe administration of DHEA at 50 mg per day to middle age in older people. In one study there was pronounced stimulation of natural killer cell activity. In the other DHEA increased insulin growth factor 1 concentrations. There was remarkable increase in the feelings of well being in about 70% of the subjects, although exactly how this was defined was unclear. The author states that enough is known or suspected to warrant investigation of DHEA(S) as an effective, worthwhile and relatively risk free replacement therapy in advancing age. 22403 [end, nut] This study was a 2 week double-blind trial of 27 subjects. Fourteen subjects received vitamin B12 at 1.5 mg of cyanocobalamin (3 times/day); 13 subjects received a placebo. No differences were found between the 2 groups. In this short term study cyanocobalamin did not appear to be an effective treatment for depression in these Seasonal Affective Disorder patients. Other data suggests that methylcobalamin may be a better hypnotic agent than cyanocobalamin. Further testing on the role of vitamin B12 in Seasonal Affective Disorder should utilize methylcobalamin versus cyanocobalamin. The treatment should be of longer duration; vitamin B12 should be used to enhance light therapy rather than as a therapy of its own. 21348 [psy] Eight human subjects between 29 and 34 years of age who were healthy nonsmokers with normal dietary habits were asked to run on a treadmill until exhaustion and blood samples were taken before and 24 hours after the run. There was a clear increase in DNA strand breakage seen in the 24 hour sample of all probands. Short term supplementation of multi-vitamin pills or vitamin E at 2400 mg total resulted in a significantly smaller increase of DNA effects in WBC of some probands. When the volunteers were given a supplement of 1200 mg of vitamin E for 14 days prior to the run, exercise- induced DNA damage was clearly reduced in all probands. In 4 or 5 subjects vitamin supplementation completely prevented the DNA damage after exhaustive exercise. The intake of vitamin E for 14 days lead to a clear increase in vitamin E serum concentrations. Malondialdehyde concentrations were significantly decreased following vitamin E supplementation but not significantly changed 15 minutes and 24 hours after the run. This data suggests that vitamin E prevents exercise induced DNA damage. It also indicates that DNA damage occurs in white blood cells after exhaustive exercise as a consequence of oxidative stress. 22431 [exe] The Environmental Working Group reported this week that laboratory tests of 8 baby foods contain residues of 16 different pesticides. These pesticides were found in lower levels than allowed by federal regulators, but the group stressed that pesticide standards are set for adults, not infants. The Environmental Working Group stated it found 16 pesticides in 8 of the 9 baby foods tested, including peaches, applesauce, and sweet potatoes. Gerber dominates the baby food market with a 69% share. A company spokesman for Gerber stated that all their products are safe. The Environmental Working Group statements were similar to that of the National Academy of Sciences for pesticide residue standards that take the health risk to infants into account and recommend the phasing out of possible carcinogenic pesticides. 22998 [env, nut] Emotions and behavior can effect several risk factors associated with cardiovascular disease. Studies have recently demonstrated the effect of social support in the prevention of cardiovascular morbidity and mortality. Increased neurohormonal activity, specifically in the adrenocortical, sympathetic, and renin- angiotensin systems, caused by stress contributes to endothelial cell dysfunction, which can be the first sign of vascular injury and the first step in the atherosclerotic process. Stress can increase platelet activity, serum levels of epinephrine and norepinephrine, and cholesterol levels. In some patients stress can lead to myocardial ischemia, and is a direct cause of coronary artery vasospasm. Increases in total systemic resistance and heart rate are consequences of perceived stress in many patients. It is noted that anger is the most important factor in a type A personality that can lead to ischemia. Peaks of labile hypertension can be as strong a risk factor for cardiovascular disease as established hypertension. 21416 [car, psy] This study evaluated 59 patients with moderate hypercholesterolemia who consumed, for 36 weeks, 20 gm of fiber per day. The fiber was a mixture of guar gum, pectin, soy, pea and corn bran. There was no significant effect on triglycerides or high density lipoprotein cholesterol. Levels of total cholesterol and low density lipoprotein cholesterol and the LDL/HDL ratio were reduced significantly during the treatment period. After 51 weeks of treatment there was a 5% reduction for total cholesterol, 9% for LDL-C and 11% for the LDL/HDL ratio. Changes were in evidence after three weeks of treatment, with maximum reductions occurring by the 15th week. 21500 [car] A high fat diet containing 50% fat was given to 28 Chinese healthy volunteers mean age of 28 years for 3 days. After the high fat diet blood glucose and cholesterol increased significantly but other parameters did not. Plasminogen activator inhibitor increased significantly after venous occlusion before or after the high fat diet but the increment was significantly less after the high fat meal. The authors concluded that the immediate effect of the short term high fat diet includes increasing plasma leve ls of glucose and cholesterol and impaired fibrinolytic response in the stress condition. 22124 [car] This is a case report of a 21-year-old female who had severe bronchospasm within minutes of beginning a work place challenge where sanding of latex parts was done. Two of 22 workers reported flushing, rhinoconjunctivitis and wheezing on exposure to sanded doll parts. These 2 workers had a history of atopy and positive immediate-type skin testing responses to raw latex extract and to common aeroallergens. The authors conclude that atopic individuals are most susceptible to developing latex sensitivities in this setting; sanding or grinding of solid latex during the manufacturing process can result in occupational asthma and rhinoconjunctivitis. 21347 [all, pul] à-amyrin palmitate which is found in the Ghanaian antiarthritic herbal preparation of Alstonia boonei, Eaies guineensis and Rauvolfia vomitoria was evaluated in an adjuvant-induced arthritic rat model. Fifty-six mg/kg of body weight was given daily for 8 days from 11 to 18 days post adjuvant or at 66 mg/kg body weight for 48 hours for 5 days from days 32 to 40. This herbal medication returned the increases in serum hyaluronate and granulocytes towards non-arthritic levels and corrected the moderate edema of adjuvant arthritis. There was reduced synovial proliferation and invasion of joints and reduced leukocyte infiltration of bone marrow and periarticular tissue in treated rats. This data suggests that à-amyrin palmitate contributes to the previously shown antiarthritic effect of herbal preparations. 22717 [rhe] This editorial notes that tobacco leaves contain significant amounts of cadmium. There is evidence that cadmium in tobacco reaches the lens of the eye. It has been shown that cataract lenses from smokers contain much more cadmium than those from nonsmokers. Smokers with or without cataract have higher cadmium levels in their blood. Smokers have lower levels of vitamin C, E and beta-carotene which lower plasma levels of vitamin C, E and beta-carotene which may explain the increased risk to the development of cataracts. In a recent study there was no decreased levels of vitamin C in smokers among either cataract or non-cataract populations nor was there a decreased level of vitamin C in the cataract lens of smokers. These results make it less likely that the causal pathway for smoking to cataracts is via vitamin C. A study by Ramakrishnan favors the idea that cadmium accumulation in the lens directly causes the damage. Other components in tobacco smoke may play a role. Cyanide and thiocyanate levels are raised in the blood of smokers and cigarette smoke is rich in free radicals and aldehydes. These radicals may cause or damage before reaching the lens but isocyanate from cyanide and aldehydes might find their way to the lens to attack the enzymes and other proteins. Isocyanate can cause lens opacification in vitro. Both aldehydes and isocyanate can modify lens proteins causing changes similar to those seen in human cataracts. If cadmium plays a major role in linking smoking to cataract then workers exposed to high cadmium levels in the cadmium plated steel industry, or those consuming cadmium rich food, such as rice in parts of Japan, might have an increased risk of cataract. 22111 [oph] This study evaluated 22 females and 7 males with moderate to severe depression with 3 day food records. Females as a group consumed a diet that provided 100% of the RDAs where the diet of the males was deficient in energy and 4 of 16 nutrients. Nutrients in the males which did not meet the RDAs included energy, vitamin B6, calcium, selenium and zinc. Vitamin B1 and riboflavin (vitamin B2) as well as vitamin A barely made the RDAs. 22180 [nut, psy] Sixty-four children between 1 month and 6 years of age received 1 gm per kg activated charcoal combined with a 6% solution of magnesium citrate 0 ml/kg, 4 ml/kg, 6 ml/kg or 8 ml/kg. Median times to first charcoal stool were 19.5 hours, 13 hours, 14 hours and 12 hours respectively from 0 to 8 ml per kg. The authors conclude that magnesium citrate reduces gastrointestinal transit time of activated charcoal stools when administered to children who receive activated charcoal for a toxic ingestion. The clinical value of this reduction needs further study. 21864 [tox] Healthy individuals were given 2 gm of vitamin C per day for 2 months. Vitamin C increased in the blood while whole blood iron, hemoglobin and serum ceruloplasmin levels significantly increased at the end of the first month, but decreased to control levels at the end of the 2nd month. With vitamin C supplementation in guinea pigs, liver ferritin iron, liver copper, serum copper and serum ceruloplasmin levels significantly decreased. There was no significant change in hemosiderin iron while blood ascorbic acid significantly increased at the end of the 2 month period. There was no significant change in serum iron and hematocrit levels. These results suggest that vitamin C has antagonistic effects on copper metabolism in guinea pigs but not in humans either on copper or iron metabolisms. 22004 [nut] In a cross-sectional study comparing birth outcomes between 1985 and 1988 high levels of chemicals were associated with birth defects including cleft palate, low birth weight and cardiac abnormalities. In-home water filters are not highly protective because in the shower chemicals can be inhaled or absorbed through the skin, according to Dr. Frank Bove, senior epidemiologist at the Agency of Toxic Substances and Disease Registry. In New Jersey, according to this study, the state's maximum levels are below the national limits, and water companies must submit samples twice yearly. If the maximum contaminant levels are exceeded additional sampling is required. Dr. Bove notes that since individuals cannot prevent the chemicals from affecting them in their homes the solution is more of a lobbying effort. 22591 [env, ped] This study evaluated 20 patients undergoing operative treatment for chronic pancreatitis (n=11) and acute pancreatitis (n=9) for levels of oxidized substances. In chronic pancreatitis conjugated dienes as well as malondialdehyde concentrations in the tissue were significantly elevated. Reduced glutathione was significantly decreased which suggests glutathione depletion to oxidative stress. In acute pancreatitis only tissue and serum malondialdehyde levels were significantly high whereas conjugated dienes remained within the normal range. Serum malondialdehyde levels correlated significantly with tissue concentrations but not with the clinical course or enzyme elevations. In chronic pancreatitis increased tissue levels of lipid peroxide products and the altered glutathione metabolism suggests ongoing peroxidation of lipids due to enhanced generation of oxygen radicals. In hemorrhagic necrotizing pancreatitis there is no proof of oxygen radical- induced lipid peroxidation. The authors conclude that in chronic pancreatitis tissue levels of lipid peroxidation products and alterations in glutathione metabolism suggest ongoing peroxidation of lipids due to enhanced generation of free radicals. Preliminary data on supplementing with antioxidants in chronic pancreatitis, or increasing glutathione tissue levels in acute pancreatitis by treating with N-acetylcysteine, indicated an improved clinical course and prevention of extrahepatic complications. Well controlled trials are warranted to confirm this. 22146 [gas] In looking at the documents from the Brown & Williamson Tobacco Corporation, the British American Tobacco Company and other tobacco interests, the documents showed a sophisticated legal and public strategy to avoid liability for the disease induced by tobacco use. The documents showed that lawyers steered scientists away from particular research avenues. It is noted if the company had been unconvinced by the causation and addiction hypothesis, than it should have had no concern that new research would provide ammunition for the enemy. The document shows that the Brown & Williamson Tobacco Company and the British American Tobacco Company knew more than 30 years ago that nicotine is addictive and that tobacco is biologically active in regards to carcinogenesis. 22885 [can, med] Overall meat consumption has grown in the United States in the last 2 decades, but the type of meat consumed is changing dramatically. The consumption of beef has declined over the last decade, while the nation has doubled its consumption of poultry since the 1970s. Americans ate more poultry per capita than any other country in the world in 1992. The country was only behind to Argentina and Uruguay in beef consumption. Meat remains the center of many American's diets, despite health experts recommendations to moderate protein and fat intake. Poultry producers have benefited enormously from consumers health concerns, marketing their products as a cheaper, healthier alternative to red meat. Americans almost doubled their annual intake of chicken between 1975 and 1992, from 26.4 pounds to 45.9 pounds, according to the USDA. Turkey consumption has doubled between 1972 and 1992. Beef consumption peaked in the late 1970s, fell during the 1980s, rose slightly last year to 67.6 pounds per person and is expected to continue rising. Beef makers have been creating lower fat varieties of beef. Over the next decade, the Agriculture Department estimates that beef consumption will decline only slightly, while pork and turkey will remain stable and chicken will continue to rise, reaching 94 pounds per person per year by the year 2005. 22052 [nut] This study evaluated 787 consecutive patients who were admitted to the hospital with firearm-related injuries. Seventy-seven percent of the firearm-related injuries occurred in men aged 15 to 44 years. The overall mean and median hospital charges per admission were $52,271 and $28,033, respectively. The overall mean and median hospital costs per admission was $13,794 and $7,964, respectively. The net income per patient ranged from an average loss of $6,980 for each patient having no insurance to an average profit of $28,557 for patients with a health maintenance organization contract. The losses sustained on non-sponsored and Medicaid patients were more than offset by the net income from patients having private health insurance, Medicare or other insurance coverage so that the average profit per admission for a firearm injury was $5,809. If the data from this institution can be extrapolated to the nation, the actual cost of providing medical care for firearm-related injuries in the United States in 1995 is projected to be 4 billion dollars. The majority of this cost will be directly paid by private health insurance. 22610 [tra] This is a case report of a 60-year-old woman who took chaparral for 10 months and developed severe hepatitis for which no other cause was found. Despite aggressive supportive therapy, the patient deteriorated and required orthotopic liver transplantation. She is now well, one year after her transplant. The authors conclude that chaparral can cause serious liver injury and fulminant hepatic failure. Herbal medication should be considered as a potential cause of liver toxicity. 21778 [gas, tox] This is a review article on the role of nitric oxide and arginine in sepsis. Nitric oxide is an unstable free radical. Nitric oxide is produced by the five-electron oxidation of 1 of the 2 equivalent guanidino nitrogens of L-arginine. It has been noted since 1981 that infections cause increased nitrate and nitrite production in man. Nitric oxide is a potent effector molecule in multiple biochemical pathways associated with sepsis in humans and in other mammals. Its functions include cytotoxicity for bacteria, fungi, and parasites, support of chemotaxis, inhibition of platelet aggregation and thrombosis, and free radical detoxification. It also mediates the hypotension of septic shock. During sepsis nitric oxide is produced through a variety of inflammatory cytokines. The induction of nitric oxide synthesis increases demand for arginine in a variety of cell types such as vascular endothelial cells, macrophages and hepatocytes. These cells respond by increasing arginine uptake and synthesis. 22616 [met] Twenty-five hundred babies are born with neural tube defects each year or 1 or 2 per 1,000 births. Many of these may also be spontaneously aborted. Anencephaly and spina bifida are the most common neural tube defects which occur in about equal frequency while encephaloceles are much rarer. Anencephaly is usually fatal before or shortly after birth while spina bifida is compatible with life though they are moderately to severely handicapped and sometimes have mental retardation. Neural tube defects occur within 1 month of conception and over 90% occur in women without a prior family history of the disorder. Published reports have noted that the incidence of neural tube defects can be reduced if folic acid is ingested prior to and through the first weeks of pregnancy. Dose ranges vary from .4 mg to 5 mg started at least 1 month prior to the conception and continue through the first month of trimester. If women continue to ingest .4 mg of folic acid each day through their reproductive lives either alone or a multivitamin preparation a daily intake of .6 of the total of folates is likely. This is probably enough to result in a substantial reduction of neural tube defects. The average diet provides about .2 mg of dietary folate per day. One can get their folic acid from food but it is noted that food folates are less well absorbed than synthetic folates. Fortification of staple foodstuff with folic acid is potentially an effective and inexpensive approach to assisting women with their intake of folic acid. The recommendation for combination of dietary folates and folic acid supplementation is unlikely to exceed .8 mg per day. The American College of Medical Genetics recommends the following: 1. Women should be advised to supplement their diets with .4 mg per day of folic acid throughout the reproductive years. 2. That the Food and Drug Administration should require that enriched cereal grain flowers are fortified with folic acid. 3. Women with a previous history of neural tube defects in their family should obtain genetic counseling concerning their risk of reoccurrence, the management of subsequent pregnancies and the appropriate folic acid intake for them. 22246 [gen, pre] This study evaluated 102 children between 4 and 35 months for early sensitization to peanut through milk formulas which contained peanut oil. Nineteen children had positive skin tests greater than 3 mm. Neither breast feeding nor formulas changed the frequency of sensitization. Vitamin D preparations in ground nut oil significantly increased the risk. The odds ratios were 5.47 in neonatal prescription and 4.82 in delayed prescription; odds increased to 8.25 in allergic children under 2 years who had received oily vitamin D preparations during their neonatal period. These results suggest that ground nut oil (peanut oil) should be left out of all foods and drugs given to infants and young children as required for infant milk formulas. 21959 [all, ped] Mercury vapor from dental amalgam has been demonstrated to exceed the sum of all other sources of mercury exposure. The effects of inorganic mercury exposure on cell function in the brain and intestinal bacteria has recently been examined. In a rat model the authors showed that ADP-ribosylation of tubulin and actin brain proteins is markedly inhibited. The ionic mercury can alter a neurochemical reaction involving the maintenance of neuromembrane structure. In a monkey model mercury from amalgam has been shown to enrich the intestinal flora with mercury resistant bacterial species which can result in resistant strains of bacteria to antibiotics. The authors conclude that from the 2 animal studies they have shown that small amounts of mercury similar to those seen in the tissues from exposure to amalgams can result in profound effects upon cell function. Also occupational exposure to mercury in dental personnel can effect reproductive function. The Dental Association maintains an viewpoint that dental amalgams are safe for human use because of their popularity over the last 150 years. The accumulating medical research continues to support the view that chronic mercury exposure from dental fillings may have important adverse health implications. 22232 [tox] This study evaluated 20 healthy young volunteers, 10 men and 10 women, in a double-blind crossover trial of 6 gm of fish oil/d, with olive oil as a placebo. Fish oil had an independent lowering effect on triglycerides and coagulation factors Vc and VIIc. Both fish and olive oil significantly raised plasminogen activator inhibitor-1 levels and lowered plasma factor Xc and fibrinogen levels in women; the women had higher initial levels than men. Mean fibrinogen levels in the women were lowered from 3.23 to 2.64 and from 3.19 to 2.66 g/l by fish and olive oil respectively. This study raises the question whether any particular fatty acid or group of fatty acids, or another constituent of fish oil such as vitamin E, may be responsible for fibrinogen lowering effect. 21998 [car] Thirty-five different red, white and rose wines in several European countries were evaluated for manganese content. There was a mean concentration of 2.7 mg manganese per liter. There was no statistically significant difference between red and white wines. One exception was the red Beaujolais wines, which had significantly higher manganese content. In citing Couzy et al., the author regards wine as a potentially good source of manganese and other trace elements. 21497 [nut] This study evaluated the phagocytosis of polymorphonuclear cells in 22 patients with inflammatory rheumatic diseases before and after 60 days of treatment with 45 mg of zinc from zinc gluconate or a placebo. In the individuals with rheumatic diseases before zinc supplementation, plasma zinc levels were found to be lower than controls and they had impaired phagocytic activity. Zinc supplementation increased the percentages of phagocytic polymorphonuclear cells and the mean phagocytic activity. This was particular evident in subjects with initially low phagocytosis. Zinc supplementation improved the impaired polymorphonuclear phagocytosis in these patients. The clinical benefit remains to be determined. 22596 [imm, reu] This is a review article of 13 studies utilizing a meta-analysis technique on the relative risk estimate for breast cancer mortality for women age 50 to 74 years of age who underwent screening mammography compared to those who did not. The relative risk was .74. None of the summary relative risk estimates for women ages 40 to 49 years were significantly less than 1.0 irrespective of screening intervention or duration of follow-up. Screening mammography significantly reduced breast cancer mortality in women between 50 and 74 years of age after 7 to 9 years of follow-up regardless of the screening interval or number of mammographic views seen. There was no reduction in breast cancer mortality in women age 40 to 49 years of age after 7 to 9 years of follow-up. Screening mammography may be effective in reducing breast cancer mortality in the 40-to-49 age group after 10 to 12 years of follow-up, but this same benefit could probably be achieved by beginning screening at menopause or at age 50. 21643 [can] This study sent out a questionnaire to 150 cystic fibrosis patients of which 80 returned the survey. Forty-seven percent followed the clinic's recommendation. In those patients not taking extra supplements serum vitamin A and E levels varied widely though most were in the normal range. Only 25% of those that responded had known insurance coverage for vitamins. Of those with minimal pulmonary disease, with a forced vital capacity of greater than 70% of predicted, they were more likely to take vitamins than those with moderate or severe disease. Malabsorption and poor consumption of vitamins A and E may result in low serum vitamin A and E levels especially in patients with moderate to severe lung disease. The authors concluded that health professionals should encourage the use of multivitamin supplements in patients with cystic fibrosis even though all the questions regarding optimal therapy have not been answered. Primary care pediatricians who care for children with cystic fibrosis should inquire about the use of vitamins and encourage them to be consistent in the use of this preventive modality. Specialty physicians who care for children with cystic fibrosis should screen for vitamin A and E deficiency on a yearly basis and should share this information with the patient and also the primary care provider. 22345 [nut, pul] This study evaluated vitamin E and serum lipid levels in 13 inpatients with Crohn's disease comparing them to 12 healthy controls. Serum concentrations of vitamin E were significantly lower in the patients with Crohn's disease compared to the controls. The red blood cell levels of the vitamin did not differ between the 2 groups. Serum concentrations of total lipids and total cholesterol were decreased in the patients with Crohn's disease. There was a significant correlation found between red blood concentrations of vitamin E and serum vitamin E/serum lipid ratios in both groups. There was no correlation between the Crohn's disease activity index and serum or red blood cell vitamin E levels. These results suggest that lowered serum vitamin E levels in patients with Crohn's disease are a symptom of hypolipidemia. Vitamin E deficiency may not be a serious problem in patients diagnosed with Crohn's disease. 21949 [gas, nut] Nineteen patients with Friedreich's ataxia, 13 patients with cerebellar atrophy and 7 with olivopontocerebellar atrophy were given an oral dose of 1,000 mg per day of the levorotatory form of hydroxytryptophan or a placebo over a 10 month period in a 10 month crossover designed trial. The levorotatory form of hydroxytryptophan showed no significant effect on cerebellar symptoms. The authors concluded that the long term treatment with a high dose of levorotatory form of hydroxytryptophan does not improve these patients symptoms of ataxia. Concordant positive effects in all tasks were found in only 2 of the 39 patients and concordant negative effects in all tasks were found in 6 patients. 22439 [neu] This reports several case studies of individuals who during vigorous sex had a spontaneous vision loss. One of the key factors was holding the breath during the period of intense excitement. The hemorrhages were probably caused by a build-up of blood that ruptured some of the blood vessels in the eye according to the researchers. The authors do know that even though these reports are noteworthy that vision loss from intensive sexual activity is probably very rare since a few such cases in light of the frequency of sexual encounters. Prevention of this condition is achieved through not holding one's breath during intense physical exertion. 22953 [oph] This placebo-controlled trial evaluated 16 healthy Caucasian women 66 years of age, who ingested a single large dose of beta- carotene at 120 mg. A single exposure of a small area of 1 volar forearm to a dose of solar simulated light resulted in a 31 to 46% reduction in skin lycopene concentration compared to an adjacent non-exposed area. The same ultraviolet dose did not result in significant changes in skin B-carotene concentration. The authors conclude that a single dose of beta-carotene increases plasma in skin beta-carotene concentrations and has no effect on plasma and skin lycopene concentrations. The amount of lycopene in the plasma and skin are comparable to or even greater than those of beta-carotene. When skin is exposed to ultraviolet light stress, more skin lycopene is destroyed compared to beta- carotene, suggesting a role of lycopene in inhibiting the oxidative damage to tissue. 22876 [can, der] This is a review article on the role of the heavy metals such as cadmium, gold and mercury and autoimmunity. In animal models cadmium treatment of rats and mice result in autoimmune responses. There is no absolute evidence that renal damage from human exposure to cadmium results in autoimmune disease. More clear cut autoimmune effects of preparations containing gold salts have been widely used in arthritis. Gold may cause autoimmune thrombocytopenia, immune complex-mediated glomerulonephritis and other autoimmune disorders. There is solid evidence that mercury can cause autoimmune disease in humans and experimental animals. There is probably a combination of factors, rather than a single mechanism involved in the induction of autoimmune responses with exposure to heavy metals. The inductive event is the exposure to the metal in an individual that is genetically predisposed. Chronic exposure is an important factor, and could take place over several months if not years. The metal may act in association with other environmental factors. Then there is probably activation of the cytokine cascade, with its effects on T and B lymphocytes. Autoantigens are released. Subsets of helper T lymphocytes are stimulated, followed by activation of the suppressor cells and proliferation of B lymphocytes. Therefore exposure to heavy metals may result in autoimmune responses and disease. It is not known why some metals can induce autoimmune responses and others do not. At present there are no published articles of autoimmune responses for silver, arsenic and cobalt. 22096 [auto] This study evaluated 90 mg per day of coenzyme Q10 on the antioxidant status in 22 healthy young subjects evaluated before and after fish oil supplementation at 3 gm per day. There was also 10 mg of vitamin E added to the mixture. Plasma coenzyme Q10 increased significantly. Thiobarbituric acid reactive substances (TBRS) decreased during the first 2 weeks of coenzyme Q10 ingestion while vitamin E increased in the 2nd week and vitamin C did not change. The decrease of thiobarbituric acid reactive substances and the presence of the majority of the orally supplemented coenzyme Q10 in the reduced form in plasma seemed to indicate an antioxidant role of coenzyme Q10 in the blood. 21820 [nut] In looking at the documents from the Brown & Williamson Tobacco Corporation, the British American Tobacco Company and other tobacco interests, the documents showed a sophisticated legal and public strategy to avoid liability for the disease induced by tobacco use. The documents showed that lawyers steered scientists away from particular research avenues. It is noted if the company had been unconvinced by the causation and addiction hypothesis, than it should have had no concern that new research would provide ammunition for the enemy. The document shows that the Brown & Williamson Tobacco Company and the British American Tobacco Company knew more than 30 years ago that nicotine is addictive and that tobacco is biologically active in regards to carcinogenesis. 22885 [can, med] This study compared 116 cases of bladder cancer to 232 controls for the risk of occupational exposure. There was a significantly elevated odds ratio for exposure to pyrolysis and combustion products. In women, there was an elevated odds ratio for ink exposure. 21594 [can] In a double-blind study, 39 hypertensive patients of 26-69 years of age were given 15mmol oral magnesium or a placebo for eight weeks. When magnesium supplementation occurred following the placebo there was a significant decrease in systolic supine and standing blood pressure. There was no decrease in blood pressure following magnesium given at the start. An independent comparison of magnesium and the placebo failed to show a significant decrease in blood pressure. The authors conclude that magnesium supplementation in mild to moderate hypertensive subjects treated with beta blockers can significantly reduce supine and standing blood pressure. 21436 [car] This is a general review article on the accumulating evidence for the use of folic acid as a preventive agent to neural tube defects in dosages ranging from 400 ug to 4 mg per day. This discussion brings up the debate about food fortification and supplementation. High levels of folate supplementation may mask pernicious amemia. Folic acid may help prevent cardiovascular disease by lowering plasma homocysteine levels. In the future the biochemical or genetic pathology of the metabolic blocks that result in neural tube defects will be discovered and it will be easier to decide whether to use widespread food fortification or individual therapy. 21574 [hem, neu, nut] This article reviews the role of prevention in health care reform. Since 1960 prevention of heart disease through lifestyle changes has had a significant impact. Congress has been slow to act on incorporation of preventive treatments in health care reform. President Clinton's package included cholesterol screening, immunizations and regular clinician visits as a means of prevention. A volunteer, Dr. Charles Francis, testified for the need for preventive benefits such as hypertensive screening, exercise and nutritional counseling and smoking cessation to reduce death and disability from cardiovascular disease, which is the nation's #1 killer. Cardiovascular disease is the leading cause of death in women; the American Heart Association highlighted a need for continued research in the area of cardiovascular risk factors for women and the rise in smoking in teenage females. Prenatal care was to be considered a covered benefit with no copayments employed; obstetricians and gynecologists would be considered a woman's primary care physician. Child care and lead screening would also be included in the preventive benefit package. The estimated cost for cardiovascular disease in 1994 by the American Heart Association is 128 billion dollars. This includes the cost of physicians and nursing services, hospital and nursing home services, the cost of medications and loss of productivity. Cigarette smoking is the major preventable risk factor for cardiovascular disease. Nutritional counseling has been recommended as essential to primary and secondary prevention of myocardial infarction as well as cardiovascular disease. Health care reform needs to include: nutrition/weight control counseling, high blood pressure, smoking cessation, physical activity and health risk assessment and educational activity. In addition, it should include signs and signals for survival during cardiovascular emergencies such as heart attack and stroke. Prevention and preventive health programs should not stop with health care reform but must be integrated into all government programs involving wellness. Schools are an ideal place for children to start to learn good lifestyle behaviors. The American Heart Association has distributed its recommended basic preventive cardiovascular services to every member of congress . . . but citizen input is needed so that the message of true health care reform through prevention is delivered to congress. 21352 [car, pre] Beans are a low-fat, high-fiber food that have significant health benefits. Beans are classified as legumes, which means vegetables that come from pods, and include beans, peas and lentils. Soybeans and peanuts are grown for their protein and oil content, while beans, lentils, lima beans, cow peas, fava beans, chick peas and common peas are generally grown as a protein source and are referred to as grain legumes. Even though there is a wide variety of beans, all beans are nutritionally similar. A half-cup serving of most cooked beans gives you 110 to 145 calories. Beans fit into the dietary goals of increasing complex carbohydrate and fiber- containing foods by being approximately 60% to 65% complexed carbohydrates and range in fiber content from 4 to 7 gm per half- cup serving. Beans are rich in soluble fiber that lower blood cholesterol and blood sugar. Half to 1 cup of beans per day can significantly reduce blood cholesterol levels and help control blood sugar levels of people who have diabetes. Beans also have insoluble fiber, which can help with digestion. Beans are a good source of the water-soluble vitamins, especially thiamine, riboflavin, niacin and folic acid. Canned beans are a good source of vitamins, but are often lower in nutrient content than home- cooked fresh beans. Beans are also good for several minerals, including calcium, iron, copper, zinc, phosphorous, potassium and magnesium. However, the body does tend to absorb minerals better from animal sources rather than vegetable sources. An average of 21% to 25% of the calories of beans come from protein, except for soy, which 34% of the calories comes from protein. Tofu contains about 10 gm of protein per 4 oz serving. You pay less for protein in beans than you do for any other source worldwide. Protein from beans isn't as well utilized as proteins from animal foods. Beans with grains or flour, such as beans in rice, corn tortillas and refried beans, and pastas and bean soup create a protein-rich meal. The fat content is very low ranging from 0.8% to 1.5%. Two exceptions are soybeans and peanuts which are 19% and 46% fat, respectively. Beans have no cholesterol, and the fat is primarily unsaturated. Soybeans are extremely rich in phytoestrogens, called isoflavones, which have been reported to prevent cancer. They may be specially effective in reducing the hormone-dependent cancers. A small amount of carbohydrate in beans is from sugars that are difficult for the intestines to digest. These sugars arrive in the large intestine and bacteria that live there feed off and ferment the sugars, producing carbon dioxide, hydrogen and a few other gasses. You can overcome 60% of the gas-producing problem of beans by soaking beans 4 to 5 hours and then discarding the water; adding fresh water in the ratio of 9 cups for every 1 cup of beans and bringing it to boil for 10 minutes and simmer it for a half hour and then, again, throw out the water; if the beans require cooking, add more water, simmer and discard the water as well. Most beans require 1 to 2 hours of cooking. Beans retain most of their nutrients through this process of soaking. The fiber content can cause some gas and, with time, will resolve itself. Any other left over gas producing problem can be relieved by using Beano, an enzyme that helps your body digest the bean sugars. 22544 [nut] This study evaluated 28 subjects with the diagnosis of simple phobia compared to 30 normal controls who were subjected to a 35% carbon dioxide panic provocation. The phobic patients reacted more strongly to the challenge of carbon dioxide than the contro7ls. This increase in anxiety was comparable to the increase of anxiety of panic disorder patients from other studies. The authors conclude that there is a constitutional þpredispositionþ that may lead to panic disorder and to the development of specific phobias. Through a self-administering apparatus subjects received, in a random order, a 7-vital-capacity breath of 35% C02/65% 02 mixture and an 80% N2/20% O2 mixture. Between the 2 inhalations the subjects had a 15 minute break outside the laboratory. It appears possible to use this test to help understand the underlying mechanisms in different anxiety disorders. 21480 [psy]7 Nine healthy women were given a basal diet supplemented with 1.5 mg of beta-carotene for 4 days. For the next 68 days, a basal diet without beta-carotene supplementation was given, and during the last 28 days of the diet each woman was given 15.0 mg of beta- carotene per day. Neither the depletion phase nor the repletion phase significantly changed the proliferation of peripheral blood mononuclear cells cultured by phytohemagglutinin or concanavalin A, in vitro production of soluble interleukin II receptors, or the concentration of circulating lymphocytes and their subsets. The authors concluded that in healthy individuals who have adequate vitamin A status, beta-carotene depletion had no adverse effect on the immune parameters tested. Supplementation resulted in no beneficial effects either. This data suggests that beta-carotene supplementation can improve immune function indexes in individuals with inadequate vitamin A intake or a previously stressed immune system, but not in individuals with adequate vitamin A intake. 21458 [imm, nut] Air pollution, airborne allergens, and changing weather can affect physical activity. High ozone levels can cause restrictive lung dysfunction and high carbon monoxide levels can impair oxygen delivery. Sulfur dioxide worsens nasal symptoms in individuals with allergies and may cause bronchospasm in those who have asthma. Airway irritation from fine particles can lead to bronchospasm. Atopic individuals can have adverse effects to fungi and pollens. Medications may be needed if a change in exercise routine does not relieve the symptoms. People who live in cities that have long term average ambient irritant levels appeared to be at higher risk for respiratory symptoms. In those doing aerobic exercise near traffic carbon monoxide congestion can raise carboxyhemoglobin levels to those found in smokers. It may be beneficial to check the media for reports of allergen and pollution levels that can help those individuals who are sensitive, to avoid peak times of concentration for outdoor exercise. It is important to choose exercises that can be performed in warm, humid environments such as a pool; if one is working out in cold weather, wear a scarf or an industrial type disposal mask over the mouth to limit the exposure of cold air and pollutants; breathe through the nose whenever possible to warm and humidify inspired air; Work out inside when pollutants or allergen levels are high outside; do 5 to 10 minutes of stretching and breathing exercises before a high intensity workout; work out slowly for the first few minutes after a warm-up; do a 10 to 15 minute cool-down after a workout. 22799 [all, pul] This is an extensive review article on the role of lipoproteins, free radicals and calcium in cardiovascular disease. LDL lipoproteins have the ability to alter cell calcium concentrations of a wide variety of cell types. The precise mechanisms of the physical interactions between LDL or its products in the cell is not clear. Most data shows that LDL can alter the transsarcolemmal calcium flux. This probably occurs through the slow calcium channel. Internal sources of calcium like those in the sarcoplasmic reticulum also appear to be altered. The effects of LDL on cellular calcium homeostasis have potential importance in physiological and disease settings. Oxidized LDL has more potential significance than native LDL in disease conditions. Free radical oxidation of LDL during atherosclerosis in ischemic conditions creates an LDL molecule that has greater potency for altering cell calcium and thereby ultimately cell function and viability. The interaction of LDL cholesterol, free radicals and cellular calcium appears to be a critical mechanism for the pathogenesis of specific cardiac diseases. Therapies that prevent their interaction will be important to identify in the future. 22481 [car] This study evaluated 15 male smokers with normal blood lipids who consumed a diet rich in polyunsaturated fatty acids providing 36% of the energy as fat. Eighteen percent of the calories came from meat, dairy products, vegetable oils and fat spreads and 18% from walnuts at 68 gm per day. The subjects consumed a vitamin-free drink daily for 3 weeks and then for 3 weeks they consumed daily supplements of orange juice which had 145 mg of vitamin C and carrot juice which had 16 mg of beta-carotene. The vitamin rich food supplements raised plasma levels of vitamin C 1.6-fold and beta-carotene 2.6-fold. Malondialdehyde was lower in copper- oxidized LDL after vitamin supplementation. The rate of LDL oxidation at lag time before the onset of LDL oxidation was not effected by antioxidant supplementation. The authors conclude that in regular smokers antioxidant vitamins partly protected LDL oxidation despite a diet rich in polyunsaturated fatty acids. Adequate antioxidant intakes could be achieved from food. 22572 [car] This study evaluated 38 patients who were requiring hemodynamic monitoring due to sepsis. After baseline measurements 19 patients received either 150 mg/kg of n-acetylcysteine or 19 received a placebo and 250 ml of 5% dextrose intravenously over 15 minutes. N-acetylcysteine but not the placebo caused a slight but significant increase in cardiac output and a decrease in systemic vascular resistance. During hypoxia there was a significant difference in the Vo2. N-acetylcysteine was 114 ml/min/m2 versus the placebo at 81 ml/min/m2 and the oxygen extraction ratio for n- acetylcysteine was 21 versus 14 in the placebo. The mean decrease in Vo2 was 11% in the n-acetylcysteine group versus 34% in the placebo group. The mean decrease of oxygen extraction was 12% in the n-acetylcysteine group versus 34% in the placebo group. N- acetylcysteine prevented a decrease in intramucosal pH and hyperoxia. N-acetylcysteine preserved a whole body oxygen uptake, oxygen extraction ratio and intramucosal pH during brief hyperoxia in these septic patients. This data suggests that pretreatment with n-acetylcysteine can prevent, to a certain degree, impaired tissue oxygenation during hyperoxia. 22461 [car, gas] This study reanalyzed the work of Thomas Chalmers in 1975 which suggested that vitamin C had no benefit in treatment of the common cold in the evaluation of 7 controlled trials. This reanalysis suggests that Chalmers' review had shortcomings. Chalmers did not consider the amount of vitamin C used in the studies and included, in his meta-analysis a study utilizing on .025-.05 gm/day of vitamin C to test subjects. In other studies Chalmers used values that are inconsistent with the origin of published results. Using data from the same studies the authors conclude that vitamin C at 1 to 6 gm per day decreased the duration of cold episodes by .93 days; the relative decrease in episode duration was 21%. The present notion that vitamin C has no effect on the common cold seems to be based in large part on a faulty review written 2 decades ago. This present study shows that the Chalmers analysis is fraught with errors and misleading data from the original studies. Studies using at least 1 gm of vitamin C showed quite a consistent benefit whereas studies with smaller doses showed less results. After the Chalmers review was published, a large number of placebo- controlled double-blind studies have been carried out. The results consistently and persuasively support the conclusion that vitamin C supplementation alleviates symptoms of the common cold. Vitamin C has a rational physiologic explanation. Vitamin C may protect against the reactive oxygen species that are produced by phagocytes during a viral infection. Also vitamin C may enhance proliferative responsive T lymphocytes and increase the production of interferon. The authors note that the safety of the general population of long term ingestion of large doses of vitamin C has been firmly established. Diarrhea and other gastrointestinal complaints are sometimes associated with large doses greater than 4 gm per day in healthy people. It is noted that people with a common infection can often ingest 30 gm per day of vitamin C without getting diarrhea apparently due to changes in vitamin C metabolism. There is evidence that large, therapeutic doses of vitamin C which start early in the course of a common cold episode significantly decrease the severity of symptoms. But the evidence showing the benefit of regular intake is much stronger as nearly all of the trials have studied the effects of regular intake. 22115 [inf, nut] This is an extensive review article on the role of calcium and blood pressure. The data has been taken since 1987. Intervention and epidemiologic studies are reviewed. Calcium in the diet, the effect of stress on calcium metabolism and calcium in hypertension of pregnancy are specific areas of focus. Calcium dysmetabolism and hypertension may be due to abnormalities in the regulation of extracellular calcium affected by parathyroid hormone, vitamin D and the renin-angiotensin system. It is noted that in pregnancy-induced hypertension there are clear abnormalities noted by hypocalciuria and large increases of intracellular free calcium. Calcium supplementation in certain studies has shown some benefit in lowering blood pressure in doses between 1 to 2 gm per day. Other than the potential development of kidney stones there appears to be no significant safety risk with calcium consumption. The dose ranges for calcium supplementation are not totally clear but there is no evidence to use more than 2 gm per day of calcium in any situation. In reports stating positive outcome to calcium supplementation, beneficial effects of calcium supplementation appear to be long lasting, but there is no documentation on long term effects of high calcium intake. From all available domestic and international data it appears that calcium from dairy products is the most reported source of calcium intake. In review, observational studies of large populations support the possibility that calcium intake plays a role in blood pressure. Contradictions occur in assessing calcium intervention studies in humans. The results have been inconsistent and in most parts negative with the exception of interventions in preeclampsia. There is not enough evidence at present to support calcium deficiency as a cause of hypertension yet its deficiency may exacerbate blood pressure/sodium sensitivity issues. Populations consuming the RDA of 800 mg of calcium per day for males and females greater than 25 years of age and 1,200 mg for pregnant females have a lower incidence of sodium sensitivity and lower prevalence of pregnancy-induced hypertension. There is no clear understanding of how dietary calcium affects blood pressure. Body weight reduction is still the single, most consistent, non- pharmacologic means of controlling blood pressure. Further research is needed on the role of sodium, calcium, potassium and magnesium, body weight and alcohol in blood pressure management. Calcium should be increased in pregnant females, especially when calcium intake is below the RDA. Intakes of calcium-rich foods, particularly dairy products, have been shown to be inversely related to hypertension. 21835 [nut, obs, ort] This is a case report of a 21-year-old female who had severe bronchospasm within minutes of beginning a work place challenge where sanding of latex parts was done. Two of 22 workers reported flushing, rhinoconjunctivitis and wheezing on exposure to sanded doll parts. These 2 workers had a history of atopy and positive immediate-type skin testing responses to raw latex extract and to common aeroallergens. The authors conclude that atopic individuals are most susceptible to developing latex sensitivities in this setting; sanding or grinding of solid latex during the manufacturing process can result in occupational asthma and rhinoconjunctivitis. 21347 [all, pul] This study evaluated cadmium concentrations in the semen samples of 12 men with proven fertility and 44 normozoospermic patients as well as 118 unselected patients of an infertility clinic and 2 industrial workers with occupational exposure to cadmium. There were no significant differences in cadmium in the seminal plasma between the 3 groups. The 2 cadmium exposed patients revealed exceptionally high cadmium levels. There was no significant correlation between seminal cadmium concentrations and conventional semen parameters or between cadmium concentrations and the fertility status of patients. Mean cadmium concentrations in seminal plasma of normozoospermic patients were higher in the group of smokers compared with the group of nonsmokers. There was a weak correlation between cadmium concentration and the number of cigarettes consumed per day. In unexposed fertile or infertile men the authors could not show a significant correlation between cadmium concentration in the seminal plasma and the ejaculate parameters measured. 22692 [rep, tox] Eighteen healthy volunteers between 18 and 33 years of age were studied for the relationship between branch chain amino acid infusions and muscle proteolysis. Eight subjects received a 16 hour overnight infusion at 1.66 umol/kg/min of branch chain amino acids. Ten subjects received a 4 hour saline infusion and served as controls. The overnight branch chain amino acid infusion increased plasma branch chain concentrations by 5 to 8 fold. This was associated with a 20 to 60% decline in arterial concentrations of other amino acids. The authors found that overnight branch chain amino acid infusions caused a sustained decline in most plasma amino acids and a net forearm release of phenylalanine. This is attributable to a sustained suppression of whole body and muscle proteolysis. This suppression occurred without stimulating muscle protein synthesis. 22492 [met, nut] In 36 nonexercising subjects with an average age of 36 years, bone mineral density was markedly weight dependent contributed to by both fat and lean tissue. Percent fat tended to be positively related to areal bone mineral density, where as the percent lean was inversely related to this index. Percent fat was positively related and the percent lean was negatively related to bone mineral density/height throughout the skeleton including the femur. In 63 exercising subjects with an average age of 33 years, fat mass and lean mass were unrelated to bone mineral density/height. The percent lean was positively correlated with bone mineral density and the bone mineral density/height in the femoral neck. The authors conclude that bone density is only associated with fat mass in sedentary women. In exercisers, femoral neck density is related to lean mass, probably due to the effects of weight-bearing exercise on both of these variables. 22669 [end, exe] This study evaluated 23 cigarette-smoking men, 11 tobacco-chewing men and 10 men who did not use tobacco, between 25 and 55 years of age who were in apparent good health for plasma and dietary vitamin C intake. Dietary intakes of vitamin C and E as well as various other lipids of tobacco-chewers, smokers and nonusers was similar in this data. Plasma vitamin C and E levels of tobacco users were significantly lower than nonusers. The use of nitrates and nitrates in chewing tobacco may have made up for the fact that chewers obtained fewer free radicals from tobacco than smokers. It is likely that tobacco smokers and chewers need to ingest more vitamin C and E than nonusers to meet their physiologic needs. Regular users of tobacco may need to consume more than the 1989 RDA for vitamin E. Tobacco users should be encouraged to eat foods that are rich in antioxidant nutrients. 22796 [nut] This study evaluated the profile of the anti-tetanus toxoid IgG subclasses in children receiving vitamin A supplementation, or a placebo, in order to assess the potential utility of the enhanced anti-tetanus toxoid response. In a randomized, double-blind, placebo-controlled clinical trial, the levels of the different anti-tetanus toxoid IgG subclasses were measured two weeks before and three weeks after immunization in 139 Indonesian preschool children between 3 and 6 years of age. Children who were given vitamin A prior to the immunization had significantly increased IgG1 levels, regardless of whether they were undergoing primary or memory reactions. In the group of children who underwent a secondary response to tetanus toxoid, vitamin A supplementation was associated with a modest, but significant, change in the level of anti-tetanus toxoid IgG3. The were only minor changes in the levels of anti-tetanus toxoid IgG2 and IgG4. Because IgG1 is a subclass that is associated with a protective response to tetanus toxoid immunization, these results suggest that vitamin A supplementation may be a safe and effective way to enhance the humoral response to tetanus toxoid and other vaccine antigens. 21784 [imm, inf] This is a review article which goes over the different results seen between magnesium salt infusions and the treatment of suspected, acute, myocardial infarction with the large ISIS-4 Study of over 58,000 patients which showed no overall benefit from magnesium, and even an increased risk compared to the Limit-2 Study in over 2,000 patients with suspected MI which reported magnesium infusion resulted in improved left ventricular function, as well as lowered short term mortality that persists in long term follow-up. The question is why did a meta-analysis of the results of magnesium infusion given to more than 1,300 patients with suspected acute myocardial infarction in small controlled studies show a dramatic reduction in mortality and also decreased post-acute MI arrhythmias that were not seen in a larger study? Did the negative findings of the Mega Trial ISIS-4 negate the findings of the protective effects of magnesium in the early trials? The results of the Limit-2 Studies lead to recommendations that magnesium is safe, simple, inexpensive, and should be entered into clinical practice without delay. Is there now no longer grounds for the use of magnesium in acute myocardial infarction as the authors of the ISIS-4 noted. The authors have reviewed 4 dissimilarities among the protocols used in the ISIS-4 and Limit Studies. 1. The time of initiation of magnesium treatment in relation to thrombolytic therapy. 2. Total dosage of magnesium used in the first 24 hours. 3. Duration of post MI magnesium infusion. 4. Treatment of control groups affect comparative mortality rates. In the smaller studies magnesium infusion was begun as soon as possible after the onset of symptoms and before subsequent fibrinolysis. The amount of magnesium infused over a 24 hour period may account for differences in adverse effects. A range in 24 hours between 50 and 65 mM may be optimal. The optimal amount of magnesium in the first 24 hours could be 55 mM and that exceeding 75 mM may increase mortality. The amount of magnesium infused over 24 hours may be a major factor in morbidity and mortality since magnesium in large doses can increase bradycardias and lead to pump failure. Magnesium treated patients in ISIS-4 when compared with controls had slightly increased 2nd and 3rd blocks, small but significantly increased heart failure and increased deaths due to cardiogenic shock that emerged during or just after the infusion. Another difference between these small and large studies is the duration of post-MI magnesium treatment. Magnesium infusions were continued after the first 24 hours but at lower doses for 12 hours, up to 2 days. A longer duration of post acute myocardial infarction magnesium infusion may be needed to prevent tachydysrhythmias. The greater than 50% reduction in mortality in the magnesium-treated patients versus controls in the small studies reflects the high mortality rate in controls possibly because antiplatelet and fibrinolytic therapy was not customarily done in the 1980s when the small studies were performed. Some of the activities of magnesium which should protect against the extension of acute myocardial infarction induced myocardial damage include antiarrhythmic and calcium- blocking effects, reduction of potassium loss, antiplatelet aggregation and vasodilation effects and protection against free radical-induced injury. The administration of magnesium promptly after the development of signs and symptoms of acute myocardial infarction and before other therapies should maximize the protective effects of magnesium. Adverse effects and increased morbidity and mortality could be minimized by excluding patients with sinoatrial and atrioventricular blocks and by not exceeding the 24 hour optimal dose range of magnesium infusion of 50 to 65 mm. This warrants further study. 22865 [car] This was a nationwide case-controlled study covering a region with 78% of all births in New Zealand between 1987 and 1990. Interviews were completed with the parents of 393 cases of infants who died with sudden infant death syndrome in the postneonatal age group and 1,592 controls. 26% of the SIDS deaths were explained by bed sharing among infants of smoking mothers and 3% by bed sharing among infants of nonsmoking mothers. The majority of SIDS deaths that are attributed to bed sharing occur among infants of smoking mothers. This data should not be interpreted to suggest that bed sharing where the mother is a nonsmoker is safe or protective against SIDS. The authors conclude that an extra 3% of sudden infant deaths could be saved by a general message for all infants not to bed share compared to messages targeted to the infants of smoking mothers. Current favorable attitudes towards infant bed sharing may jeopardize the acceptance of other cot death prevention messages if it is perceived that the evidence does not justify a general recommendation against this practice. 22675 [ped] This study evaluated 125 Ethiopian immigrants to Israel and found 5 women who had hypocalcemia. All 5 had low serum levels of 25 hydroxyvitamin D3 and high parathyroid hormone levels. In 4 or 5 patients there was evidence of vitamin D deficiency detected during pregnancy or lactation. Treatment with vitamin D2 for 4 to 13 months resulted in clinical improvement and partially corrected the biochemical abnormalities. But low levels of vitamin D and elevated parathyroid hormone persisted. In one case the vitamin D2 therapy was 2000 I.U. of vitamin D orally per day. The authors conclude that vitamin D deficiency among female Ethiopian immigrants to Israel can be due to either dark skin or low calcium and vitamin D intake or possibly both. 22326 [nut, obs] The mean percent of energy from total sugars consumed in the United States is 18% according to data from the 1987-1988 U.S. Department of Agriculture Nationwide Food Conservation Program. This data does not include lactose consumption. When the sugar is distributed among the other food groups, 39% come from the "others" group. Consumers of high amounts of sugar do not necessarily have poor quality diets. In the European Union the mean percent energy intake for all sugars is 15.2%. The top 5 sources of sugar contributed 68% of sugar intake but only 11% of fat intake in the United Kingdom. Even though sugar intake varies among the major developed nations there is a consistent inverse relationship between fat and sugar intakes and the scarcity of individuals achieving dietary guidelines. 22764 [nut] This study randomized 260 patients receiving 4 gm of fish oil postoperatively compared to 251 controls. Serum triglyceride concentrations were lowered by 19.1% in the fish oil group but there was no influence on the concentration of cholesterol or apolipoproteins A-I and B-100 seen. The concentration of plasma glucose and serum Insulin and C-peptide were not effected by the fish oil. The activity of liver enzymes increased slightly but significantly in the fish oil group. There was no difference in serum concentrations of thiobarbituric acid reactive substances seen. No adverse effects of long term fish oil supplementation assumed to be of clinical importance were seen. 22105 [car] This study evaluated 39 individuals. Twenty received 10 gm of fish oil per day; 19 received 10 gm of Italian olive oil as a placebo. The number of angina attacks decreased by 41% in the fish oil group and were not changed in the olive oil group. Glyceryl trinitrate consumption decreased in the fish oil group but did not in the olive oil group. Exercise tolerance time increased significantly in the fish oil group 8 and 12 weeks after start of the treatment. There was a smaller but insignificant increase seen in the olive oil group. Serum triglycerides were reduced by 22% at 8 weeks after fish oil supplementation and 11% at 12 weeks. There was a slight increase in triglycerides in the olive oil group. There was no significant change in platelet aggregation ratio or beta thromboglobulin in either group. The authors note that dietary supplementation with low doses of fish oil appear to have beneficial effects on the clinical status of patients with coronary artery disease and in particular angina pectoris. Fish oil had no impact on platelet function. 21511 [car] The National Association of Physicians For The Environment (NAPE) has as their mantra: "Pollution prevention is disease prevention". Founded in 1993, the NAPE membership consists of 19 medical societies and organizations. Presenters at this conference outlined how pollution affects almost every organ system. The airways and lungs are affected by exposure to tobacco smoke, diesel, gas, and rubber by-products. Hearing loss from noise exposure may be aggravated by inhalation of solvents such as toluene, or exposure to asphyxial gases and heavy metals. Exposure to hardwood dust and formaldehyde used in furniture making and leather tanning increases the risk of intestinal and other adenocarcinomas. Men exposed to high levels of wood dust and formaldehyde have 5.3 times higher cancer risks. Heavy metals such as lead, cadmium, and mercury may affect renal function. Halogenated hydrocarbons, organic solvents and pesticides may cause acute or chronic nephrotoxicity. Cancer of the urinary tract has been associated with exposure to aromatic amines from dyes, exhaust fumes, solvents, fuel oils, and tobacco smoke. The pesticide DDT affects the reproductive system by mimicking the action of estrogens in the body. In wild animals, low-level exposure to DDT has been found to feminize males in utero, causing future low-sperm counts. Lead exposure can reduce sperm counts and inhibit testosterone synthesis, and cause peritubular fibrosis. Exposure to lead, carbon disulfide, asbestos, arsenic, ozone, cadmium, vinyl chloride, fluorocarbons, freon and pesticides can result in hypertension and cardiac arrhythmias. Carbon monoxide can make hemoglobin useless for oxygen transport. Lead and arsine can damage the membranes of red blood cells, resulting in anemia. Benzenes and volatile polycyclic hydrocarbons have been associated with leukemia. The extensive use of pesticides and herbicides may be associated with Hodgkin's disease, non-Hodgkin's lymphoma, and aplastic anemia. Chlorofluorocarbons thin the ozone layer, allowing ultraviolet radiation to reach the earth, thereby promoting skin cancer. It is estimated that every 1% decrease in ozone translates in a 2% increase in ultraviolet B radiation, and a 2% increase in skin cancer. During pregnancy, lead stored in bone is released and can harm the fetus. Lead also causes skeletal growth abnormalities. Lead exposure has been associated with antisocial behavior. Pollution may increase stress. It has been noted that there is an association between high pollution levels and psychiatric emergency calls. Beryllium exposure causes a granulomatous form of lung disease. Excessive ozone inhalation may result in lung inflammation. Polycyclic aromatic hydrocarbons suppress immune function. Toluene diisocyanate can trigger hypersensitivity reactions. Mercury has been found to trigger autoimmune disease in the kidneys and lungs. Pollutants can aggravate allergies by their effect on T suppressor cells, T helper cells and the B cells and immunoglobulins. Pollution may increase airway inflammation in asthmatics. Low ozone levels may increase bronchial sensitivity in asthmatics. 21696 [all, imm, pul, tox] This study evaluated childhood cancer in Shanghai, including 82 lymphoma cases and 159 acute leukemia cases compared to controls. After adjusting for variables there was a reduction in risk of lymphoma among children who were breast fed as infants versus those who were not. The reduction in risk was greater for children who had been breast fed longer and was specifically noticed in children with Hodgkin's disease and to the cases diagnosed before 6 years. There was no risk reduction with breast feeding in acute leukemia. 22735 [can, car] This article comments on the role of polyunsaturated fatty acids and cancer. It is noted that polyunsaturated fats have been long regarded as protective against heart disease. Polyunsaturated fats are present in fish oil and a wide range of plant oils and can be divided into 2 classes, depending on the position of the last double bond in the hydrocarbon chain. In those from fish oil this double bond is at the third carbon from the end. These are termed omega-3 fatty acids. In those from the plant sources the last bond is at sixth carbon from the end, giving rise to the omega-6 fatty acids. These two groups of fatty acids behave very differently in the body. Omega-3 fatty acids may help prevent diabetes, cardiovascular disease, hypertension, stroke, hypertriglyceridemia and ulcerative colitis. Fish oil may also be protective against cancers such as bowel and breast cancer. Omega-3 fatty acids have been shown to normalize rectal mucosal cell proliferation in adenoma patients after only 12 weeks of treatment. Mechanisms by which fish oil have their beneficial effects include their effect on protein turnover, on protein kinase C activity, and on HDL-2 levels. Fish oil has also been shown to have a beneficial effect on prostaglandin synthesis. Fish oil eicosanoids generally give rise to the EPA series while plant polyunsaturated fatty acids generally go into the arachidonic acid series. Studies have shown that in patients with colorectal adenomas or carcinomas, the rectal mucosal levels of prostaglandin A2 and arachidonic acid are higher than in control patients. The serum levels of prostaglandin E2 are higher in colorectal cancer patients with metastatic disease than those with only local tumors. EPA replaces arachidonic acid in the gut mucosal tissues and suppresses prostaglandin E2 formation. Nonsteroidal anti-inflammatory agents such as sulindac and piroxicam inhibit the production of prostaglandin E2, cause adenoma regression in familial polyposis patients, and reduce the incidence of large bowel cancer. There are also interesting reports on the use of omega-3 fatty acids in the treatment of metastatic breast cancer. The mechanism by which nonsteroidal anti-inflammatory agents are beneficial in the prevention of colorectal cancer may be similar to that of omega-3 fatty acids. 21676 [can] This study evaluated 104 lactose intolerant patients who had residual discomfort despite lactose elimination after their appropriate diagnosis. Intolerance of fructose or sorbitol was documented in 17.3% and 18.3% of the Crohn's disease and colonic diverticulosis, respectively. Intolerance to both fructose and sorbitol occurred in 41.4% and was independent of sex. The authors conclude that additional carbohydrate intolerance contribute to postcibal discomfort in more than 75% of lactose-intolerant patients who remain symptomatic in spite of adherence to lactose- intolerance regimes. Sixty-two percent of the patients benefited from appropriate dietary measures and enzyme replacement for lactose intolerance, while only 40% of those who were fructose intolerant and 47% who were sorbitol intolerant benefited. 21818 [gas] Fractures from osteoporosis are a major public health problem in the western world. Most of the cost calculations are based on hip fractures. The estimates are between 10 and 20 billion dollars annually in the United States and 0.3 billion in England and Wales. These totals are likely to underestimate the cost of the disease. Within 50 years the cost of hip fractures alone in the United States may exceed 240 billion. There appear to be age-specific increases in incidence which will only aggravate the problem. It is not known to what degree interventions can control this epidemic of fractures in the next century. The author says the future is bleak, since in many countries the incidence is increasingly magnifying the effects of societal aging seen currently in most parts of the world. 21933 [end, ort] This study evaluated 131 patients with histopathologically confirmed basal cell cancer and 200 cancer-free controls with nonmalignant skin disorders. The use of any vitamins, but specifically multivitamins and vitamins A, C and E was associated with a reduced risk of basal cell cancer. After controlling for variables, which include age, sex, use of tobacco, lifetime number of severe sunburns and skin actinic lesions, regular vitamin supplementation was associated with significantly reduced risk of basal cell cancer. The odds ratio decreased as the regular use and daily dosage of the supplements increased. This was especially noted with vitamins A and E. Vitamin supplementation was not associated with alterations in DNA repair. More rigorous studies are needed to establish the effect of supplemental vitamins. 21415 [can, der] Elevated homocysteine levels occur frequently in end stage renal disease. This study evaluated total fasting homocysteine, plasma levels of folic acid, pyridoxal 5'-phosphate, plasma vitamin B12 levels, serine, total cholesterol and HDL cholesterol, glucose, creatinine in 24 end stage renal disease patients on dialysis compared to 24 age-matched controls. Mean plasma homocysteine levels were considerably higher in end stage renal disease patients versus controls. End stage renal disease patients were 3 times more likely to have elevated homocysteine levels. These elevated homocysteine levels persisted in end stage renal disease patients despite normal to super normal B vitamin status. Plasma serine levels below the 10th percentile of the control distribution were found in 75% of the end stage renal disease patients. Oral L-serine was given in 3 or 4.5 gm tablets taken twice daily for a total of 3 gm in 1 patient and 4 gm in 3 patients for 7 days and then stopped. This resulted in a 37% increase in plasma serine levels but no effect on plasma homocysteine in 4 end stage renal disease patients with supernormal levels of plasma serine and hyperhomocysteinemia. It is possible that reducing hyperhomocysteinemia might reduce cardiovascular consequences of end stage renal disease. Supplementation trials need to be done to confirm this. 22221 [car, nep] This is a review article on the role of homocysteine lowering by specific vitamins and its effect on cardiovascular disease. There is rapidly accumulating evidence that moderate levels of elevated homocysteine are an independent risk factor for cardiovascular disease. All but 5 of 47 studies, including a total of more than 15,000 investigated patients and controls, support this issue. Both basal elevated levels of homocysteine and hyperhomocysteinemia revealed by a methionine load are markers for increased cardiovascular risk. The finding of a dose-response relationship between plasma homocysteine concentration, over its full range, and the relative risk for the prevalence or severity of cardiovascular disease strongly supports causality. Dietary vitamins B6, B12, folate and their synthetic oral counterparts pyridoxine hydrochloride, cyanocobalamin and folic acid serve as precursors of the cofactors for homocysteine metabolism, Pyridoxal 5 Phosphate, methylcobalamin and methyltetrahydrofolate respectively. In man, vitamin B6 deficiency does not seem to result in basal hyperhomocysteinemia. Folate and vitamin B12 deficiency may result in considerable hyperhomocysteinemia which is rapidly normalized after replenishment of the deficient vitamin. Even within the normal ranges, levels of serum or red cell folate and serum vitamin B12 are strong determinants of plasma homocysteine concentrations. In untreated cases of genetically caused severe hyperhomocysteinemias (homocystinuria), life threatening cardiovascular events are frequent. In general, cofactor supplementation for homocysteine metabolism results in considerable decreases of plasma homocysteine concentration. Renal insufficiency results in moderate hyperhomocysteinemia and accelerated atherosclerosis. Several studies have shown that oral treatment with folic acid at 5 to 10 mg per day reduces renal hyperhomocysteinemia by a factor of 30 to 60%. Oral vitamin B6 has no homocysteine lowering effect in this condition. In fact, the authors found that pyridoxine treatment at 300 mg per day for 18 weeks in uremic patients with low plasma pyridoxal phosphate levels lead to significantly increased plasma homocysteine concentrations. In 2 studies which included 28 non- vitamin deficient healthy subjects, mostly with normal plasma homocysteine levels folic acid at 5 mg per day for 2 to 4 weeks resulted in lowering of homocysteine levels in all but 2 of the individuals. Reductions were in the average larger than 30% and were most marked with high homocysteine levels. Oral treatment over 2 weeks with pyridoxine at 40 mg per day or vitamin B12 at 1 mg per day had no homocysteine lowering effect. In another study, vitamin B6 at 120 mg a day had no effect over 6 weeks on plasma homocysteine concentrations in 16 healthy subjects. The authors propose that the homocysteine lowering effect of folic acid in nonfolate deficient subjects is from the excess folic acid after conversion to methyl tetrahydrofolate increases the rate by which homocysteine is remethylated to methionine. In contrast, excess B12 and folic acid will not decrease plasma homocysteine and unless deficiency is present as these vitamins serve as coenzymes, not as cosubstrates as does methyltetrahydrofolate. In 2 recent studies of patients with vascular disease and hyperhomocysteinemia and 1 study in normal normohomocysteinemic patients the combination of vitamin B6 at 100 to 250 mg per day and folic acid at 5 to 10 mg per day reduced plasma homocysteine levels by a mean of 51, 38 and 30% respectively. In a group of consecutive patients with acute myocardial infarction of whom most were normohomocysteinemic and all had normal serum folate levels, we found that 2.5 mg and 10 mg of folic acid over 6 weeks had a similar homocysteine lowering effect in both plasma homocysteine effect. In both groups plasma homocysteine was reduced by a mean of 27%. Reductions were seen in all but 2 patients, both with low homocysteine values. With few exceptions the response to folic acid was proportional to the pretreatment homocysteine levels. Hyperhomocysteinemia due to vitamin B12 deficiency does not respond to folic acid therapy. It has been shown that men with moderate hyperhomocysteinemia in most cases had suboptimal plasma vitamin B12 and folate levels. Such men were in a 6 week trial either given folic acid at .65 mg per day, pyridoxine at 10 mg per day or cyanocobalamin at .4 mg per day or a combination of these vitamins. Most but not all responded to the folic acid. Pyridoxine had no homocysteine lowering effect in this study whereas cyanocobalamin decreased plasma homocysteine by a mean of 15%. All responded to the combination by a mean of homocysteine reduction of 50% though homocysteine values were not normalized in all subjects during this short trial. There are recent results showing that high dose parenteral administration of cobalamin decreases plasma homocysteine in subjects with normal vitamin B12 levels. There have been several studies which show that patients with premature cardiovascular disease frequently respond to oral methionine loads of 100 mg per kg of body weight with abnormally high increases in plasma homocysteine concentrations. This may be more suggestive of a vitamin B6 deficiency compared to an elevated basal homocysteine concentrations which may be more indicative of vitamin B12 and folic acid deficiency which effects homocysteine remethylation. Several studies have shown that pyridoxine at 100 to 250 mg per day improves abnormal methionine loading tests in many but not all patients. With a combination of vitamin B6 at 100 to 250 mg per day and folic acid 5 to 10 mg per day all the patients responded and the abnormality was mostly normalized. Methionine rich meals normally cause slight increases in plasma homocysteine concentrations. It is quite possible that subjects with abnormal methionine loading tests are also responding abnormally to methionine rich meals leading to transient periods of hyperhomocysteinemia which could be normalized with combined pyridoxine and folic acid therapy. For several reasons it appears wise to combine folic acid with vitamin B12. Folic acid seems to reduce all but low homocysteine levels. Cyanocobalamin will probably secure the full responsiveness of folic acid. In vitamin B12 deficiency erroneous treatment with folic acid may correct the hematologic abnormalities but result in a deterioration of vitamin B12 neuropathy. Before starting therapy vitamin B12 deficiency must be excluded and the combination must contain a dose of cyanocobalamin high enough to prevent the occurrence of vitamin B12 deficiency even if complete intrinsic factor deficiency develops during the course of therapy. At least .2 mg of cyanocobalamin need to be administered. For intervention studies in cardiovascular disease a combination of 1 mg of folic acid and .4 mg of cyanocobalamin is probably sufficient for effective homocysteine lowering. This combination will probably be innocuous and also normalized hyperhomocysteinemia in most patients and reduce the normal homocysteine values leading to a shift of the entire homocysteine distribution towards lower values. This is important because there appears to be a relationship between plasma homocysteine concentrations and the risk of cardiovascular disease. 22074 [car] The Mediterranean diet, which is high in fruit, vegetable and grain consumption, typically has 1 or 2 drinks per day and appears, when consumed responsibly, to be an important component of the Mediterranean diet and a component of a healthy lifestyle. Alcohol consumption clearly reduces the risk of cardiovascular disease in populations throughout the world and may contribute to lower rates of cardiovascular disease among residents of Mediterranean countries. 22555 [car, nut] This is a retrospective study of the occurrence of cancer in 28,511 patients with cystic fibrosis between 1985 and 1992 in the United States and Canada. Thirty-seven cancers were seen in the North American cohort during the 164,764 person-years of follow- up as compared with the expected number of 45.6 yielding a ratio of observed to expected cancers of 0.8. Thirteen digestive tract cancers were mentioned as compared with an expected number of 2 for a ratio observed to expected cancers of 6.5. In Europe 11 of 39 cancers originated in the digestive tract yielding a positive association between digestive tract tumors and cystic fibrosis. The authors conclude that there is an overall risk in patients with cystic fibrosis of developing digestive tract cancers even though cancers in general appear to have a similar frequency. 21853 [can] This Italian study of 755 cases of lung cancer compared to 755 controls showed that air pollution is a moderate risk factor for certain histologic types of lung cancer. Compared to those in a residential area, those in a rural area had a relative risk of .6. The relative risk was 1.5 for residents in the center of the city and 1.4 for residents in the center of industrial areas in Trieste, Italy. In the center of the city, the excess risk was almost completely related to small cell carcinoma and to large cell carcinoma. 22659 [can] This is a review article on the role of vitamin C and beta- carotene as oxidants and pro-oxidants. Falls in antioxidants such as vitamin C during the acute phase response may be of benefit against endogenous and exogenous stresses by removing a potential pro-oxidant. In these acute phase response situations a low normal concentration of circulating nutrients may be adequate or even optimal for antioxidant requirements. Low concentrations of plasma ascorbic acid may be adequate to maintain the antioxidant properties of the plasma since a mechanism for regeneration that reduces vitamin C has been demonstrated. There is no such mechanism for beta-carotene. But also there is probably no oxidized form of carotenes that have been demonstrated in the tissue. During the acute phase response the host may compromise its own requirements to attain a short term advantage over a suboptimal situation. This may not remain an indefinite advantage. In chronic disease nutritional support may be desirable but it cannot necessarily be assumed to be the case. 21821 [nut] The foundation of a healthy weight gaining program is the combination of a strength training and high carbohydrate calorie packed diet. Some type of aerobic exercise can be beneficial for your heart but it won't help you gain weight. According to the American College of Sports Medicine the best fitness program is aerobic and strength training exercise plus a diet that will help you build lean, toned, tight muscles rather than flabby fat. It used to be thought that eating a lot of dairy products and plenty of meat was needed to build muscle. This diet was most popular during the generation of the 80 body builders which consumed not only lots of meat but lots of fat. The belief was that the more protein in the diet would result in the more muscles that could be built. It has been found that it is not fat and protein that builds muscles but calories, particularly carbohydrates. A study of a liquid, high calorie diet supplement on weight gain, body composition and the strength of weight lifters, compared to those who didn't take the supplement, found that the supplemented group gained considerably more weight than the control group. This was approximately 3« more pounds. The supplemented group also doubled lean body mass, gained more strength and lost .9% fat. The supplemented group consumed approximately 830 calories more per day than the control group. The control group ate a greater percentage of their calories from fat where the supplemented group consumed a greater amount from carbohydrates. Protein requirements are increased when a person exercises. Extra protein can aid strength training by helping build muscle and may aid endurance by replacing the protein that is oxidized for energy during exercise. Strength training athletes need to consume between .6 and .8 gm per pound per day and endurance athletes about .5 to .6. Multiply your body weight and pounds by these numbers to find out how much protein you need each day. There was no evidence that more protein than this will give you additional muscle building advantage. A cup of milk or 1 egg contains 8 grams of protein. One ounce of beef, chicken, fish, nuts or seeds contains 7 grams and a half a cup of dried beans contains 7 grams. It takes energy to do the exercise that builds muscles. You need at least the amount of calories that you burn to maintain your weight. It is important to add 2500 calories per week or 400 to 500 calories per day to build 1 pound of muscle. Gradually increase your calories. Quick weight gain can add fat pounds and not lean body mass pounds. One should consume 60 to 65% of their calories from carbohydrates. This helps fuels your muscles for exercise and helps promote muscle growth and increases the chance that the weight you gained will be more muscle than fat. One should replace the carbohydrates in your muscles within 30 minutes to 2 hours after exercise. Fat should be less than 30% of your calories. It is important to eat all your meals and you may try a meal replacement if missing meals becomes a problem that you can't seem to overcome. The best kinds have about 350 to 400 calories or 65 of their calories from carbohydrate and 20 to 25% of the day's worth of protein, vitamins and minerals. Snack is an important part of a weight gain program. One might need 2 or 3 snacks per day to meet your goals. Snacks can be light meals. Meal replacement sports drinks may also be useful as a snack. Try not to use more than a meal replacement sports drink for more than 1 meal or 1 snack per day. The slower the weight gain the more likely that the weight gain is from muscle and not fat. 22138 [exe, ort] In a double-blind trial, 85 patients, 5 to 39 years of age, with mild lung disease were randomly assigned to receive either ibuprofen or placebo orally twice daily for 4 years. Patients who randomly received ibuprofen had a slower annual rate of change in their FEV1 than patients assigned to placebo; and weight was better maintained in the group that received ibuprofen. Among patients who took ibuprofen for 4 years and had at least a 70% compliance rate, the annual rate of change in FEV1 was even slower. This group of patients also had a significantly slower rate of decline in forced vital capacity, the percentage of ideal body weight and chest radiograph score. There was no significant difference between the ibuprofen and placebo groups in the frequency of hospitalization. One patient was withdrawn from the study because of conjunctivitis, and one because of epistaxis related problems. The authors conclude that in patients with cystic fibrosis and mild lung disease, high- dose ibuprofen, taken consistently for 4 years, significantly slows the progression of lung disease without serious side effects. Antiinflammatory agents represent a new treatment for patients with cystic fibrosis and mild lung disease, and can enhance conventional therapy. The cost of this ibuprofen therapy is less than $200 annually. 22072 [gen, pul] This is an extensive review article on the role of recycling drinking water from secondary waste water. Based on the studies, the authors concluded that properly treated secondary waste water can be recycled into safe drinking water for public consumption. 21505 [env, tox] This is a review article on the ergogenic properties of Ginseng. Ginseng has been used for several thousand years in the Orient as a tonic, prophylactic agent and "restorative." Ginseng has been used by athletes as an ergogenic aid for many years even though there has been an absence of compelling research in support of its use. Most of this evidence is testimonial. In certain animal models ginseng, or its active components, may prolong survival to physical or chemical stress. There has been a wide variety of dosages used in animal and human studies. Dosages in animal models tend to be 10 to 100-fold higher. Research in humans with ginseng has had numerous methodological and statistical shortcomings. There remains a need for well designed trials using this substance as an ergogenic aid. There is no basis to ban ginseng since it has not been shown to enhance performance. 22630 [exe] This study evaluated samples of the isthmic part of the uterus from 42 pregnant patients not in labor, 31 patients in regular labor during a cesarean section and 37 premenopausal patients in whom a hysterectomy was performed. Magnesium concentrations dropped significantly during labor. Calcium concentration showed no significant change in the tissues during labor. Magnesium and calcium concentrations were significantly higher during pregnancy. The distribution of electrolytes in the myometrium differed significantly in from those the corpus, isthmus and cervix uteri. The authors conclude that the electrolyte concentration, specifically calcium and magnesium, in the myometrium depends on the place of removal. A low magnesium concentration in pregnant human myometrium might be a cause of premature labor. It is noted that during pregnancy there is a physiologic accumulation of water in the tissues and a significant decrease in the excretion of magnesium through the kidney. Magnesium requirement of the growing fetus, the placenta and the myometrium can be taken care of with a balanced diet, though in some cases magnesium supplementation may be needed. If premature labor ensues, increasing the magnesium calcium ratio may help in the shortening of the use of beta- mimetics. 22623 [obs] Dental amalgams are the most important source of mercury exposure in the general population. There is debate about their systemic health effects. Mice that were inbred genetically to be susceptible to mercury-induced immune aberrations had implanted in their peritoneal cavity 8-100 mg silver amalgam or silver alloy for 10 weeks or 6 months. Chronic hyperimmunoglobulinemia, serum IgG antibodies targeting the nucleolar protein fibrillarin and systemic immune complex deposits developed in a time- and dose-dependent manner after implantation of the amalgam or alloy. Splenocytes from the mice that had the implanted amalgam or alloy showed an increased expression of class II molecules. Splenic T & B cells were affected in a dose-dependent manner. At 10 weeks of low dose and 6 months of high dose amalgam implantation, there was a strongly increased mitogen-induced T & B cell proliferation; whereas at 10 weeks of high dose implantation there was a decreased proliferation. Mercury and silver accumulated in the spleen and kidneys after amalgam implantation. The authors conclude that dental amalgam implantation in the physiological body context results in chronic stimulation of the immune system with induction of systemic autoimmunity in genetically sensitive mice. Implantation of silver alloy not containing mercury also induced autoimmunity. This latter finding suggests other elements, especially silver, have the potential to induce autoimmunity in genetically susceptible vertebrates. It is possible that accumulation of heavy metals from dental amalgams and other sources can lower the threshold of an individual metal to elicit an immunologic aberration. The authors believe that, under appropriate genetic and environmental body burden conditions, heavy metal exposure from dental amalgams may contribute to immunologic aberrations which could lead to autoimmunity. This particular study showed that dental silver amalgam and silver alloy implanted in the physiologic tissue of the peritoneal cavity released enough metals to adversely affect the murine system. 21923 [env, tox] This study evaluated 1,089 women who received phenytoin (Dilantin) for eclamptic convulsions compared to 1,049 women who received magnesium sulfate. Ten of the women in the Dilantin group had convulsions compared to none in the magnesium sulfate treated group. The therapy in the magnesium regimen consisted of a 10 gm loading dose of 50% magnesium sulfate intramuscularly followed by a maintenance dose of 5 gm intramuscularly every 4 hours. For women with severe preeclampsia, an additional 4 gm loading dose was given intravenously. The phenytoin regimen included a 1,000 mg loading dose infused over a period of an hour, followed by a 500 mg oral dose 10 hours later. With each regimen, the anticonvulsive therapy was continued for 24 hours postpartum. The authors conclude that magnesium sulfate is superior to Dilantin for the prevention of eclampsia in hypertensive pregnant women. This research supports the long practice of using magnesium sulfate in the prevention of eclampsia. 22907 [gyn, obs] The author reports the use of capsaicin on 6 occasions in 4 female patients in an attempt to relieve severe pain of the loin pain/hematuria syndrome. Patients were given a 1 mmol/L solution of capsaicin in 30% ethanol in saline delivered via a balloon catheter sited to obstruct the lower ureter or continuously irrigated via an ureteric catheter with the tip sited in the pelvis. Treatment was continued for 30 minutes. Patient A had a gradual return of pain after 5 months and was retreated at 1 year. Patient B had bilateral loin pain. All the patients have reported loss of pain shortly after treatment but have felt as though they had been kicked in the kidney. This may be due to edema of the renal pelvis. All the patients have immediately complained of severe bladder pain and this may be due to the effects of capsaicin which gets into the bladder but in low dose because it is diluted by the fluid used for cystoscopy. Patient C developed bleeding from the opposite kidney during the treatment and had severe pain on this site immediately after treatment. After the first treatment the patient had a brief rise in skin temperature to 40ø centigrade. Vital signs were normal. All patients reported short lived attacks of pain on 2 or 3 occasions requiring pethidine but freedom from long term continuous pain. All of the patients stopped taking their regular opiod analgesia. It has been reported, by others, that a capsaicin solution can be used in the bladder to modify the detrusor reflex arch in paraplegia. The same concentration of capsaicin solution has been used in the patients the author sees. This study suggests the usefulness of this treatment in both groups of patients and an indepth study into the safety and efficacy of this treatment in the larger group of patients with renal pain is under way. 22142 [nep] Ten healthy subjects who swim regularly in ice cold water during the winter were evaluated before and after this short term whole body exposure. There was a drastic decrease in uric acid concentration seen during and following the exposure to cold stimulus. It is believed that the uric acid decrease is caused by its consumption after formation of free radicals. The level of oxidized glutathione and the ratio of oxidized glutathione/total glutathione increased after cold exposure. Baseline concentration of reduced glutathione was increased and the concentration of oxidized glutathione was decreased in the erythrocytes of winter swimmers as compared to those of non winter swimmers. This appears to be an adaptation to repeated oxidative stress. Hardening is the exposure to a natural stimulus, in this case thermal, which results in an increased tolerance to stress and disease. Exposure to repeated intensive short-term cold stimuli is often utilized in hydrotherapy, which is used in physical medicine for hardening. 21866 [met] Six severely burned men and five young, healthy men were evaluated to assess the acute and protracted adaptive response of peripheral glutamine kinetics to a severe injury. The catabolic hormones epinephrine, cortisol, and glucagon were infused simultaneously into the femoral arteries of the 5 healthy volunteers, simulating the hormonal secretion that occurs during severe injury. Whole-body glutamine flux increased to a similar extent in both the burn patients and the volunteers following catabolic hormone infusion. The hormonally stimulated acute stress in the volunteers induced a significant efflux of glutamine from the leg by greatly increasing the rate of glutamine appearance. The burn patients had a significant decrease in their rate of glutamine appearance and achieved a similar net loss of glutamine from the leg only by a compensatory decrease in peripheral glutamine consumption. These results suggest that in the acute stress response, skeletal muscle preferentially releases glutamine from its free intracellular pool. As this reserve becomes depleted, net glutamine efflux is maintained by decreasing its rate of muscle glutamine utilization. These results suggest a failure of muscle to enhance de novo glutamine synthesis and support the conclusion that glutamine is a conditionally essential amino acid during critical illness. 21792 [sur, tra] This study evaluated 3 gm of eicosapentaenoic acid in a double- blind, randomized, multi-center study that was given from 12 to 14 weeks of gestation onwards. Sixty-three subjects with a history of intrauterine growth retardation with or without pregnancy-induced hypertension in the previous pregnancy were evaluated. One-third of the women developed pregnancy-induced hypertension and þ of the infants had a birth weight below the 10th centile. There was no difference between the placebo and in the eicosapentaenoic acid group. This study suggests that 3 gm of eicosapentaenoic acid daily does not prevent the recurrence of intrauterine growth retardation or pregnancy induced-hypertension in a high risk population. Future studies should utilize higher doses of EPA preferably in combination with a diet low in arachidonic acid. 22189 [obs, ped] This study evaluated the relationship between dietary intake of fish and mercury, as well as the mercury content of hair and urine to the risk of acute myocardial infarction and death from coronary heart disease or cardiovascular disease. This relationship was evaluated in 1833 men between 42 and 60 years of age who were free of clinical coronary heart disease, stroke, claudication, and cancer. Seventy-three men had an acute myocardial infarction in 2 to 7 years. Of the 78 deceased men, 18 died of coronary heart disease and 24 died of cardiovascular disease. Men who had consumed local nonfatty fish species had elevated hair mercury contents. Dietary intakes of fish and mercury were associated with significantly increased risks of acute myocardial infarction and death from coronary heart disease, cardiovascular disease, and any death. Men in the highest tertile of hair mercury content had a 2-fold higher risk of acute myocardial infarction and 2.9-fold increased risk of cardiovascular death compared to those with lower hair mercury content. The 24 hour urinary mercury excretion had a significant independent association risk of acute myocardial infarction. Both hair and urinary mercury were associated significantly with immune complexes containing oxidized LDL. This data suggests that the high intake of mercury from nonfatty freshwater fish and the subsequent accumulation of body burden mercury are associated with excess risk of acute myocardial infarction and death from coronary heart disease and cardiovascular disease. Mercury may enhance lipid peroxidation and therefore increase risk. The significance of this study is multi-faceted. Fish consumption may be healthy in general, but some fish may contain substances that are not healthy for the cardiovascular system. These findings suggest that mercury, even in subtoxic amounts, is a risk factor for coronary and fatal cardiovascular disease. Increased mercury would increase coronary heart disease by promoting lipid peroxidation. The prevention of additional pollution of the environment by mercury, and the eventual removal of environmental mercury, should be considered as measures in the prevention of cardiovascular disease. 21714 [car] This article reviews the chemistry and action of thioctic (à- lipoic) acid which is a drug used for the treatment of diabetic polyneuropathy in Germany. It is believed that thioctic acid acts as an antioxidant and interferes with the pathogenesis of diabetic neuropathy. These authors found that thioctic acid had a prolonged dose-dependent inhibitory effect on CU2+-catalyzed ascorbic acid oxidation and also increased the partition of copper into N-octanol from an aqueous solution suggesting that thioctic acid forms a lipophilic complex with CU2+. Thioctic acid also inhibited CU2+ catalyzed liposomal peroxidation. Thioctic acid inhibited intracellular H202 production in erythrocytes challenged with vitamin C. This study suggests that thioctic acid may work not only by reducing thioctic acid to dihydrolipoic acid may also operate via CU2+-chelation. 22859 [met] This double-blind study evaluated 7 probable Alzheimer's disease patients treated with 3 gm per day of acetyl-L-carnitine for 1 year, 5 probable Alzheimer's disease patients treated with a placebo and 21 controls. Compared to Alzheimer's diseases patients on the placebo, the acetyl-L-carnitine-treated patients showed significantly less deterioration in their Mini-Mental Status and Alzheimer's Disease Assessment Scale test scores. The decrease in the phosphomonoester levels observed in both the acetyl-L-carnitine and placebo Alzheimer's disease groups at entry was normalized in the acetyl-L-carnitine treated-, but not in the placebo-treated, patients. Similar normalization of high- energy phosphate levels was seen in the carnitine group, but not in the placebo-treated group. This research is the first in vivo demonstration of a beneficial effect of a drug on both the clinical and central nervous system neurochemical parameters in Alzheimer's disease. 22822 [neu] Eight children with severe persistent anemia unresponsive to oral iron therapy were treated with intravenous iron saccharate. Hemoglobin rose from 8 g/dL to 11 g/dL. The concentration of serum transferrin receptor, an indicator of iron deficiency, before intravenous therapy, correlated with the increase in hemoglobin. The authors conclude that intravenous iron saccharate could be an effective treatment for chronic anemia in this condition, especially when the iron deficiency is not responsive to oral iron. 22050 [rhe] This study evaluated 14 saphenous vein grafts from patients who needed a second revascularization procedure. Dermatan sulfate is the main glycosaminoglycan seen in both normal saphenous veins and saphenous vein grafts. These tissues also contain chondroitin sulfate and heparin sulfate. Even though the total amount of glycosaminoglycans decreased in the grafts compared with the normal saphenous veins, the grafts showed an increase in the relative amount of dermatan sulfate and chondroitin sulfate. Heparan sulfate was decreased, compared with normal controls. These findings suggest that the involvement of blood vessel glycosaminoglycans are involved in the process of atherosclerosis. This suggests that vein grafts, with regards to glycosaminoglycans, appear to be effected by a similar mechanism to arteries in the atherosclerotic process. 22041 [car] This study evaluated over 47,000 male professionals between 40 to 75 years of age and found physical activity inversely associated with a risk for colon cancer. Body mass index was directly associated with a risk for colon cancer independently of physical activity. Waist circumference and waist to hip ratio were strong risk factors for colon cancer. Height was also associated with a higher risk for colon cancer. These results suggest an inverse association between physical activity and the risk for colon cancer whereas height and obesity, particularly abdominal adiposity, are associated with an elevated risk. 21988 [can, exe] This article reviews a variety of problems that occur in adolescents which include, iron deficiency, obesity, the eating disorders anorexia nervosa, and bulimia nervosa. This article also reviews the Food Guide Pyramid. Rapidly growing adolescents are at high risk for inadequate zinc levels, especially if they limit their intake of flesh foods and dairy products. Pregnant teenagers are specifically susceptible to zinc deficiency due to rapid cell division and growth of the developing fetus and continued personal growth. Pregnant adolescent vegetarians are at risk for calcium, iron, zinc, vitamin B12, and vitamin D deficiency. Adolescents who are capable of getting pregnant should take at least .4 mg of folic acid per day but no more than 1 mg per day. Smoking should be discouraged. 22830 [nut] Chromium is necessary for carbohydrate and lipid metabolism. Insufficient dietary chromium is associated with adult onset diabetes and cardiovascular disease. The dietary intake of chromium is generally less than the recommended safe and adequate intake. The consumption of simple sugars and refined foods increases the problem of insufficient dietary intake since these foods are not only low in dietary chromium but also enhance chromium loss. Pregnancy, strenuous exercise, infection, physical trauma and other forms of stress increase chromium's utilization. Supplementation of chromium has lead to significant improvement in glucose tolerance, HDL cholesterol, insulin and insulin binding. Chromium supplementation can normalize blood sugar. When chromium is supplemented to individuals with elevated blood sugar after a glucose load, there is a decrease in blood sugar. Hypoglycemic individuals respond to supplemental chromium by an increase in their hypoglycemic blood sugar values, enhanced insulin binding and the reduction of their hypoglycemic symptoms. 21620 [car, end, nut] This study evaluated the relationship between milk intake and preeclampsia in over 9,200 pregnant females. A logistic regression analysis showed the relative risk for those who drank 2 glasses of milk per day had the lowest risk. The relative risk for those drinking 1 glass a day was similarly low at 1.2. For those who drank less than 1 glass of milk per day the risk was higher at 1.9. Women drinking 3 or more glasses of milk per day also showed increased risk of 2.0 as did those who drank 4 more glasses per day at a risk of 1.8. The increased risk associated with low milk intake is consistent with studies showing reduced blood pressure with calcium intake. The increased risk with high intake has not been shown previously. 22160 [gyn, obs] Cancer incidence continues to rise. The death rate from cancer continues to rise. The average survival for cancer patients with breast cancer, lung cancer, prostate cancer and ovarian cancer has not changed greatly in the last decade. Yet the combined budget for this nation's yearly war on cancer exceeds 5 billion dollars. The Federal government's national cancer program is approaching 2 billion dollars per year. The American Cancer Society's fundraising efforts are reaching a new high and the spending by the pharmaceutical industry on cancer research and new drug development for cancer treatments are reaching an all time high. Medical care expenditures for cancer treatments continue to increase in spite of record levels of support for cancer education and prevention treatment. Publicly there is doubt about the nation's war on cancer succeeding. There have been improvements with regards to survivors for leukemia, lymphoma, germ cell cancer and to a lesser extent renal cancer, melanoma and other selected less common cancers. The overall evidence regarding gains in common cancers of mankind has been very modest or next to nothing. Despite education and prevention there have been no major changes in the rising incidence of cancer in spite of more than 20 years of warnings on certain habits such as smoking, plus extensive education on early warning signs of cancer. Perhaps this problem should be treated as a business problem; when a business fails, individuals go to the client base and ask what is wrong and why. More attention might be paid to the physicians, nurses and patients on the front line of the "war" on cancer. It is questioned whether the National Cancer Program has become an entitlement program for institutions, physicians and scientists whose livelihood depends upon the funding process. The author states the patient needs to be put first. We need to ask patients, their families and support groups, consumer organizations and practicing oncologists and oncology nurses what the real needs are to deliver a high quality "battle plan" for the war on cancer. It needs to be determined whether pharmaceutical companies are truly facilitating the efforts on the war or whether their influences are inhibitory. The author suggests a "blue ribbon panel" be established to directly advise the present government on how to go about changing the battle plan for the war on cancer. This panel should not include individuals that are currently entitled by the government, American Cancer Society programs, or the pharmaceutical industry. This panel should include patients and consumer representatives, physicians, nurses, biotechnology industry representatives and younger minds who are less rigid about cancer research and the treatment process. A type of patient-centered approach might ultimately result in a reduced incidence of cancer and improved survivorship for cancer patients. 22015 [can] Air pollution, airborne allergens, and changing weather can affect physical activity. High ozone levels can cause restrictive lung dysfunction and high carbon monoxide levels can impair oxygen delivery. Sulfur dioxide worsens nasal symptoms in individuals with allergies and may cause bronchospasm in those who have asthma. Airway irritation from fine particles can lead to bronchospasm. Atopic individuals can have adverse effects to fungi and pollens. Medications may be needed if a change in exercise routine does not relieve the symptoms. People who live in cities that have long term average ambient irritant levels appeared to be at higher risk for respiratory symptoms. In those doing aerobic exercise near traffic carbon monoxide congestion can raise carboxyhemoglobin levels to those found in smokers. It may be beneficial to check the media for reports of allergen and pollution levels that can help those individuals who are sensitive, to avoid peak times of concentration for outdoor exercise. It is important to choose exercises that can be performed in warm, humid environments such as a pool; if one is working out in cold weather, wear a scarf or an industrial type disposal mask over the mouth to limit the exposure of cold air and pollutants; breathe through the nose whenever possible to warm and humidify inspired air; Work out inside when pollutants or allergen levels are high outside; do 5 to 10 minutes of stretching and breathing exercises before a high intensity workout; work out slowly for the first few minutes after a warm-up; do a 10 to 15 minute cool-down after a workout. 22799 [all, pul] This reviewed by regression analysis the role of stearic acid on cholesterol. Unlike other long chain saturated fatty acids stearic acid had no effect on total cholesterol and lipoprotein cholesterol concentrations in men and women. Monounsaturated fat significantly decreased total serum cholesterol and LDL cholesterol and increased HDL cholesterol. The long chain saturated fatty acids of the 12:0, 14:0 and 16:0 structure significantly increased total cholesterol, LDL-C cholesterol and HDL-C cholesterol. Stearic acid which is an 18:0 long chain saturated fatty acid is unique and does not increase plasma total cholesterol and LDL cholesterol concentrations. The authors believe that the previous variable cholesterolemic effect seen from monounsaturated fats are probably due to the relatively high amount of 12:0-16:0 saturated fatty acids in the diet which can obscure the monounsaturated fatty acid response. 22305 [car] The author notes that approximately þ of flu patients are ill from 5 to 14 days while another þ do not recover from the flu as rapidly. Complains of lassitude, lethargy, hypersomnia or insomnia and a few muscle pains and headaches are common symptoms. This post flu syndrome subsides after 3 to 4 weeks. One mg of vitamin B12 intramuscularly can resolve this post flu syndrome literally in a matter of hours. The author suggests a double-blind study be done. 22154 [inf] This is a retrospective study of the occurrence of cancer in 28,511 patients with cystic fibrosis between 1985 and 1992 in the United States and Canada. Thirty-seven cancers were seen in the North American cohort during the 164,764 person-years of follow- up as compared with the expected number of 45.6 yielding a ratio of observed to expected cancers of 0.8. Thirteen digestive tract cancers were mentioned as compared with an expected number of 2 for a ratio observed to expected cancers of 6.5. In Europe 11 of 39 cancers originated in the digestive tract yielding a positive association between digestive tract tumors and cystic fibrosis. The authors conclude that there is an overall risk in patients with cystic fibrosis of developing digestive tract cancers even though cancers in general appear to have a similar frequency. 21853 [can] This study evaluated 94 patients at entry and at 5 year follow-up for the relationship between hyaluronic acid and osteoarthritis of the knee. Hyaluronic acid levels were significantly related to disease duration, minimum joint space and previous surgery at entry. Those who progressed with the disease had significantly higher levels of hyaluronic acid at baseline compared with those whose disease had not progressed. This data suggests that hyaluronic acid levels predict disease outcome and osteoarthritis of the knee and confirm that a serum level of keratin sulfate is not a useful prognostic marker for osteoarthritis. 22658 [art] This article reviews the role of complex carbohydrates and exercise. A low glycemic index food, such as rice, lentils or pasta formed from complex carbohydrates, should be consumed before prolonged exercise. This diet is able to provide an advantage over a high glycemic index diet, such as glucose. This may be related to the slower rate of oxidation which saves carbohydrate substrate for muscle metabolism at a later stage of exercise. Also, lower insulin release helps maintain higher levels of plasma glucose and free fatty acids which could delay the decrease in muscle glycogen levels. Some studies have shown that the endurance time to exhaustion is prolonged after ingestion of a complex carbohydrate meal. 22575 [exe] An association between periodontal disease and coronary artery disease has been reported. This letter to the editor comments that in the Nutrition Examination Survey I Epidemiologic Follow- Up Study a white blood cell count greater than 8,100 cells/mm3, compared to less than 6,600 cells/mm3, was associated with a 31% increase in the risk-adjusted incidence of coronary heart disease in white men and women, and a 43% increase in risk-adjusted total mortality in white men aged 45 to 74 years. It is possible that chronic periodontitis may produce a long-term increase in white blood cell count. Fifty patients with periodontal disease had significantly higher levels of white blood cells and fibrinogen than 50 age-matched controls with healthy periodontal tissue. Serum albumin concentration greater than 44 gm/L was associated with a reduced adjusted risk of coronary heart disease. The risk of total mortality was similarly reduced in individuals with high serum albumin concentrations. It is known that chronic bacterial infection is associated with increased serum gamma globulin and decreased serum albumin concentrations. Additional studies are needed to examine the effect of dental health, dental health interventions, and other variables on the emerging coronary risk factors of white blood cell count and serum albumin levels. 21726 [car] This study evaluated the relationship between calcium intake, bone mineral density and strength in 162 girls, 10 to 15 years of age, from 10 secondary elementary schools. Calcium intake was significantly associated with bone mineral density in the 15-year- old group, but no relationship was seen in the 13-year-old group. Grip strength was significantly and positively related to bone mineral density and bone mineral content. Calcium intakes above 1,000 to 1,200 mg per day had no further effect on bone mineral density. Grip strength, an indicator of overall body strength, was significantly associated with bone mineral density. 21829 [nut, ort] Cancer incidence continues to rise. The death rate from cancer continues to rise. The average survival for cancer patients with breast cancer, lung cancer, prostate cancer and ovarian cancer has not changed greatly in the last decade. Yet the combined budget for this nation's yearly war on cancer exceeds 5 billion dollars. The Federal government's national cancer program is approaching 2 billion dollars per year. The American Cancer Society's fundraising efforts are reaching a new high and the spending by the pharmaceutical industry on cancer research and new drug development for cancer treatments are reaching an all time high. Medical care expenditures for cancer treatments continue to increase in spite of record levels of support for cancer education and prevention treatment. Publicly there is doubt about the nation's war on cancer succeeding. There have been improvements with regards to survivors for leukemia, lymphoma, germ cell cancer and to a lesser extent renal cancer, melanoma and other selected less common cancers. The overall evidence regarding gains in common cancers of mankind has been very modest or next to nothing. Despite education and prevention there have been no major changes in the rising incidence of cancer in spite of more than 20 years of warnings on certain habits such as smoking, plus extensive education on early warning signs of cancer. Perhaps this problem should be treated as a business problem; when a business fails, individuals go to the client base and ask what is wrong and why. More attention might be paid to the physicians, nurses and patients on the front line of the "war" on cancer. It is questioned whether the National Cancer Program has become an entitlement program for institutions, physicians and scientists whose livelihood depends upon the funding process. The author states the patient needs to be put first. We need to ask patients, their families and support groups, consumer organizations and practicing oncologists and oncology nurses what the real needs are to deliver a high quality "battle plan" for the war on cancer. It needs to be determined whether pharmaceutical companies are truly facilitating the efforts on the war or whether their influences are inhibitory. The author suggests a "blue ribbon panel" be established to directly advise the present government on how to go about changing the battle plan for the war on cancer. This panel should not include individuals that are currently entitled by the government, American Cancer Society programs, or the pharmaceutical industry. This panel should include patients and consumer representatives, physicians, nurses, biotechnology industry representatives and younger minds who are less rigid about cancer research and the treatment process. A type of patient-centered approach might ultimately result in a reduced incidence of cancer and improved survivorship for cancer patients. 22015 [can] This study evaluated oral arginine supplementation utilizing 30 g of arginine aspartate (net free arginine intake 17 g/d) in 30 subjects or a placebo in 15 subjects for 14 days. The arginine aspartate was dissolved in 60 ml of an aromatic syrup. Two weeks of arginine supplementation lead to an elevation of serum insulin-like growth factor concentrations and improved positive nitrogen balance compared to controls. The arginine supplemented group showed a decreased total serum cholesterol with a reduction in the low density lipoprotein but not the high density lipoprotein fraction which resulted in an increase in the low to high density lipoprotein fraction. No other adverse consequences were noted. The data suggests that oral arginine supplementation may be used safely in elderly humans. Recent data suggests that arginine supplementation may be beneficial in enhancing immune response in trauma and cancer patients and may also promote wound healing. This data showed that pharmacologic doses of arginine had no side effects in the elderly and maintained positive nitrogen balance while reducing cholesterol levels. 22617 [can, car, cri, ger, imm] It is noted in Canada that the utilization of alternative therapies ranges between 20 and 34%. 563 subjects in Alberta, Canada were interviewed. Chiropractic was the most common form of alternative medicine sought after by this group . . . more common, in fact, than visits to a specialist. Chiropractic care was significantly related to age group. This suggests that adults were more likely to see a chiropractor than children. There is a strong relationship between utilization of chiropractors by parents and their children. Women were more likely than men to see a chiropractor or another alternative practitioner. Those who had seen a chiropractor had visited a general practitioner more often than those who had not seen a chiropractor. This study found a larger proportion of adults using alternative practitioners than had been found previously in Alberta (32.3% in this study versus 19% in 1990). It is noted that the majority of alternative medicine users also utilize conventional medicine, so the term þcomplementaryþ may be more appropriate than þalternativeþ medicine. The authors conclude that relatively few people in this rural area use alternative approaches other than chiropractic, which is an insured service under the Alberta Provincial Health Plan. Under said plan, physicians are allowed to refer patients to chiropractors. 21353 [med] This study 121,700 female nurses between 30 and 55 years of age who began the Nurses Health Study in 1976. In 1982 toenail clippings were requested from this cohort and 62,641 participants with no history of cancer returned toenail clippings. Over a 41 month follow-up period 503 cases of cancer other than breast cancer or nonmelanoma skin cancer were analyzed. No adverse association was seen between selenium levels in the toenails and cancer risk. Toenail selenium was not inversely associated with any cancer at any major site which included uterine and colorectal cancer, melanoma, ovarian cancer or lung cancer. There was a nonsignificant positive association observed at several sites. The authors concluded that toenail selenium levels were not inversely associated with cancer risk in the study. 22377 [can] At least a dozen clinical trials have now been done with vitamin A supplementation. These trials have shown a reduction in severe morbidity and mortality from infectious diseases among children who have acute measles or who are from areas where vitamin A deficiency is endemic. Vitamin A deficiency is an immunodeficiency characterized by alterations in immunity, changes in mucosal surfaces, impaired antibody responses, changes in lymphocyte subpopulations, and altered T- and B- cell function. Vitamin A and its metabolites have immune enhancing properties and have been shown to potentiate antibody responses to T-cell-dependent antigens, increase lymphocyte proliferation responses to antigens and mitogens, inhibit apoptosis, and restore mucosal cell surfaces. The specific immune-response genes that may be regulated by vitamin A through its metabolites have yet to be identified. There is a gap in knowledge regarding the effect of vitamin A deficiency and treatment on the function and phagocytosis of natural killer cells. An estimated 124 million children are deficient in vitamin A, and therefore at higher risk of death from infectious diseases. Improvement in vitamin A nutriture is expected to prevent 1.3 to 2.5 million deaths annually, and a periodic high-dose of vitamin A is now widely practiced in many countries where vitamin A deficiency is endemic. High-dose vitamin A supplementation for children with acute measles is expected to contribute to a reduced mortality. Measles is responsible for 2 million deaths annually. Whether vitamin A will be able to reduce the severe morbidity and mortality from malaria and tuberculosis is yet to be discovered. It is estimated that between 38 and 108 million individuals will be infected with HIV by the year 2000. It is not known whether vitamin A supplementation has the ability to alter the outcome of these individuals. Vitamin A costs approximately 2 cents per capsule, and is one of the most cost-effective means of reducing childhood mortality. It remains to be determined whether vitamin A holds promise for the treatment of major immunosuppressive diseases. 21783 [imm, inf] Twenty-four hour urine samples from 63 volunteers between 16 and 49 years of age were evaluated for parameters of acid-base status to characterize the relationship between renal acid secretion and urine pH. The calculated acid-forming potential of more than 100 frequently consumed foods and beverages was evaluated. Among raw fruits, the base-forming potential was similar to that of vegetables. Along with fruits, fruit juices, and vegetables, alkali rich, low-phosphorous beverages have the lowest potential renal acid load values. These foods are followed in the order of gradually increasing average potential renal acid load values by alkali-poor or low phosphorous beverages, fats, oils, milk and non- cheese diary products, bread, noodles, and flour. Fish, meat,meat products, and cheese, are food groups with the highest potential renal acid load. An exchange of only a few foods can dramatically alter the dietary intake of acid equivalents. The calculation methodology which is primarily based on the potential renal acid load allows for the appropriate prediction of effects of diet on acidity of the urine. 22792 [gen] This study evaluated over 1,800 Mexican-American females 20 years of age or older who participated in the Hispanic Health and Nutrition Examination Survey for the relationship between menopause, pregnancy, smoking, and blood lead levels. Blood lead levels were considerably higher among current smokers and postmenopausal women. The number of pregnancies had little impact on blood lead levels among premenopausal women. Among postmenopausal women, never-pregnant women had a higher blood lead level than those who had ever been pregnant. The largest increase was observed among smokers. In postmenopausal women those with recent menopause had blood lead concentrations of 1.4 ug/dl higher than those whose menopause occurred more than 4 years previously. This data, along with an overall slow decline in blood lead levels with each year after menopause suggests that lead is being immobilized at rates consistent with patterns of bone loss placing women with recent menopause at a higher risk for higher blood levels. This leads to the question whether women with larger stores of lead are at an increased risk for bone loss and the development of osteoporosis since it is known that lead can disrupt bone mineral metabolism. 22956 [end] This is a case report of an 83-year-old female who was admitted for increasing congestive heart failure and worsening renal function. She denied a history of digoxin use and was given a loading dose of 1 mg of digoxin over 14 hours on the day after admission and an additional 125 mcg on day two. Six hours later she developed multiple ventricular arrhythmias including ventricular tachycardia. She then divulged a prior history of digoxin treatment. Her serum digoxin level was greater than 6.2 nmol/L 8 hours after her last dose. Her admission digoxin level was found to be at the very upper border of normal. She was admitted to the coronary care unit and given an IV bolus of 2.47 gm (10 mmol) of magnesium sulfate, injected over 5 minutes. Five minutes later her ventricular tachycardia stopped and she developed a junctional rhythm with a ventricular rate of approximately 90 bpm. Within a few minutes a stable rhythm emerged. After approximately 15 minutes she developed intermittent bursts of non-sustained monomorphic ventricular tachycardia lasting up to 30 seconds without any clinical deterioration. Another 2.47 gm of magnesium sulfate was given over 5 minutes followed by a return of the junctional bigeminy. She developed, over the next several days, episodes of nonsustained ventricular tachycardia. On day 9 her serum digoxin level was at 3.0 nmol/L and she was discharged on day 10. Sixteen days after her admission her digoxin was 1.8 nmol/L. Digoxin binds to and inhibits the sarcolemma sodium/potassium ATPase pump leading to increased intracellular calcium concentrations, which enhances myocardial contractility. Magnesium enhances the action of the sodium/potassium ATPase pump without affecting the binding of digoxin. Intravenous magnesium has been shown to stop the digoxin-toxic cardiac arrhythmias in patients without overt heart disease. Hypermagnesemia is unlikely to occur with an initial bolus of 10 to 20 mmol of magnesium, but possibly could occur with continuous infusions or with repeat doses in patients with digitalis toxicity. Intravenous calcium is the antidote and should be kept available. 21745 [car] This study evaluated a single, oral dose of DHEA (dehydroepiandrosterone) at 500 mg on sleep stages, sleep stage- specific electroencephalogram, power spectra, and concurrent hormone secretion in 10 healthy young men. DHEA administration resulted in a significant increase in rapid eye movement (REM) sleep, whereas all other sleep variables remained unchanged compared with the placebo condition. There was significantly enhanced EEG activity in the sigma frequency range during REM sleep in the first two hour sleep period after DHEA administration. The EEG power spectra of non-REM sleep were not affected. These results suggest that DHEA administration has a mixed GABAa- agonistic/antagonistic effect, which is exerted either directly or through the DHEA-induced changes in steroid metabolism. REM sleep has been implicated in memory storage. The enhancement of REM sleep in the present study suggests the potential clinical usefulness of DHEA in age-related dementia. 21707 [end, neu] This was a randomized, double-blind, crossover trial, evaluating gastrointestinal symptoms in 30 individuals who reportedly had severe lactic acidosis and said they consistently had symptoms after ingesting less than 240 ml of milk. Twenty-one percent of the subjects were classified as having lactose intolerance and 9 as being able to absorb lactose. Gastrointestinal symptoms were minimal during the study period. When the periods were compared, there was no statistically significant difference in the severity of the 4 gastrointestinal symptoms which included bloating, abdominal pain, diarrhea, and flatus. For the lactose malabsorption group the difference in episodes of flatus per day were 2.5. There was a high degree of compliance. The ability to digest lactose was measured by the subject's N-alveolar hydrogen concentration after ingesting 15 gm of lactose and 250 ml of water. The subjects then received either 250 ml of lactose-hydrolyzed milk containing 2% fat or 250 ml of milk containing 2% fat and sweetened with aspartame to the approximate taste of lactose-hydrolyzed milk. The authors conclude that those individuals who identify themselves as severely lactose intolerant may mistakenly attribute a variety of abdominal complaints to lactose intolerance. When lactose is limited to the equivalent of 240 ml of milk or less a day, symptoms are likely to be negligible and the use of lactose-digestive aids are unnecessary. 22776 [gas] This letter to the editor comments on possible beneficial effects of breastfeeding on neurological status at nine years of age. This may be caused by longer-chain polyunsaturated fatty acids in breast milk that are absent in most formula milks. The authors have evaluated maternal smoking during pregnancy and breast feeding afterwards in 1,331 mothers of twins from the Netherlands. Maternal smoking during pregnancy and breast feeding were assessed 3 to 6 months after and 2 years after the birth of twins. There was a highly significant association indicating that 39% of the mothers who bottle-fed their children smoked, whereas 27% of the mothers who breast fed their children smoked during pregnancy. The frequency of breastfeeding rises with increasing socio-economic status. The relationship between bottle feeding and smoking during pregnancy suggests the possibility that the association between formula-feeding and neurological status at age 9 is mediated by smoking behavior of the mother. The observations on nicotine exposure in animals suggest a mechanism by which smoking during pregnancy could negatively affect neurological outcome. 21796 [neu] This study evaluated over 15,700 middle-aged adults for vitamin A intake utilizing a food frequency questionnaire. With only one exception, vitamin A intake was unrelated to airway obstruction in all smoking categories. Although there is a theoretic basis that vitamin A intake may prevent obstructive lung disease, this study did not show that relationship. 21528 [pul] This is a case report of a 42-year-old female who was evaluated for severe anemia and neutropenia. A malabsorption syndrome was confirmed by serum carotene of 48 mcg/dl (normal range is 60 to 200 mcg/dl) and a stool fat of 8 g/24 hours. Serum ceruloplasmin was less than 5 mg/dl with a normal of 21-53 mg/dl and serum copper was 12 mcg/dl (normal is 85 to 155 mcg/dl). Urinary copper was 17 mcg/24 hours (normal is 15 to 50 mcg/24 hours) and serum zinc was 182 mcg/dl (normal is 50 to 150 mcg/dl). Three milligrams of elemental copper as copper chloride were administered intravenously twice a week for a total of 10 weeks with subsequent normalization of serum copper and ceruloplasmin levels to 115 mcg/dl and 34 mg/dl, respectively. The peripheral blood counts normalized, and a repeat bone marrow showed normal erythroid and myeloid maturation. Copper deficiency needs to be included in the differential diagnosis of causative anemia and/or neutropenia in individuals with a history of gastric resection or without evidence of intestinal malabsorption disorder. 21808 [hem] This study evaluated 24 hour urine aluminum and lead excretion, plasma aluminum levels, and whole blood lead levels in 30 healthy women. The levels were tested before and during treatment with calcium citrate at 800 mg of elemental calcium per day. During calcium citrate therapy, urinary aluminum excretion and plasma aluminum levels increased significantly. There were no changes in urine or whole blood lead levels. The authors conclude that calcium citrate significantly increases absorption of aluminum from dietary sources. The long term effects of calcium citrate supplementation need to be assessed. 21445 [nut, tox] This was a retrospective study of 68 familial Mediterranean fever patients with amyloidosis and proteinuria who benefitted while receiving colchicine at a dose of 1.5 mg per day or more. This dosage was only beneficial in patients with initial serum creatinine levels of less than 1.5 mg/dl. These results suggest that amyloidosis of familial Mediterranean fever may be beneficial prior to the onset of the uremic stage to colchicine treatment. 21506 [rhe] Cobalamin serum assays were evaluated in 1,599 subjects; low serum cobalamin concentrations were noted in 84 of these patients. Only sixteen of these subjects with low vitamin B12 levels were confirmed as deficient. The positive predictive value of low cobalamin levels in this population was 22.2%. The authors feel that the positive predictive value of the cobalamin assay is low. Low cobalamin levels should not be used to justify lifetime parenteral therapy or to rule out other conditions that may mimic vitamin B12 deficiency. The impact of the false positive serum cobalamin assay results on patient care is significant, especially when one considers that nearly 4 out of 5 patients with low serum cobalamin concentrations have no clinical evidence of deficiency. 21701 [nut] This study evaluated the effects of a diet low in saturated fat and cholesterol in serum lipid concentrations and growth in 1062 healthy 7-month-old infants in a randomized study. Every 1 to 3 months families in the intervention group received dietary advice aimed at getting the calories below 30 to 35% energy as polyunsaturated, monounsaturated and saturated fat in a 1:1:1 ratio and a cholesterol intake of less than 200 mg per day. The control group received an unrestricted diet. Between 7 and 13 months, serum cholesterol and non high-density lipoprotein cholesterol concentrations did not change significantly in the intervention group but increased substantially in the control group. Daily intakes of energy and saturated fat were lower in the intervention group than in the control group at 13 months. The intake of polyunsaturated fats was higher in the intervention group. Growth did not differ between the 2 groups and was normal for their age. Serum cholesterol concentrations fell significantly in the parents of the intervention group. The authors conclude that increases in serum cholesterol and non high density lipoprotein cholesterol concentrations that occur in infants between 7 and 13 months of age can be avoided with individualized diet with no effect on the child's growth. The authors main hypothesis is that the introduction of a low fat diet early in life will make a low fat diet more acceptable later on. These researchers are going to follow the effects of a low saturated fat and cholesterol diet in these children. 21865 [car] This article did a MEDLINE search for clinical reviews and origin of studies on the use of vitamins in medicine. The primary years searched were between 1990 and 1994. Several recommendations for the use of vitamins for the treatment and prevention are reported which include topical vitamin A derivatives (tretinoin) for the treatment of acne and age related skin damage, oral vitamin A derivatives for cystic acne and psoriasis, vitamin D3 for treatment and prevention of osteoporosis in postmenopausal females, topical vitamin D for psoriasis patients, and niacin for serum cholesterol. Folate appears to reduce the risk of neural tube defects during the preconception time of pregnancy. Recent evidence suggests there may be a benefit of vitamin C, E and beta-carotene in the prevention of atherosclerosis and cancer. To enhance vitamin D levels aside from taking oral supplements, 5 to 10 minutes of sunlight 4 to 5 times per week is appropriate. One of the concerns of vitamin D treatment is hypercalcemia. Vitamin D3 derivatives seem to be a viable alternative for the prevention of postmenopausal osteoporosis in those who are unable or unwilling to take estrogen replacement therapy. Niacin has been used to lower cholesterol since the mid 1950s. Niacin is the most effective drug in elevating HDL levels. Niacin also lowers triglycerides and LDL levels. It has low cost and it is efficacious. It has not been used as extensively as other more expensive agents partly because the pharmaceutical industry has promoted other more profitable agents. Because nicotinic acid is available over-the-counter at very reasonable prices minimal promotional activities have been attempted. Side effects such as cutaneous flushing, gastric irritation, nausea, itching, skin rash and elevation of liver enzymes have also reduced its use. Five grains of aspirin or 400 mg of ibuprofen 30 minutes before taking niacin can reduce the flush. One can start on small doses of 50 to 100 mg 3 times per day and eventually build up to 1 to 3 gm orally 3 times daily. The doses for folic acid to prevent neural tube defects begin at .4 mg per day. The author concludes by noting that antioxidant therapy is one of the most exciting in medicine. Toxicities generally do not occur from the antioxidants. 22392 [can, car, der, end, gyn, neu, obs] This study evaluated serum zinc levels in 20 adolescent gymnasts, 12 to 15 years of age. This group had low serum zinc levels when compared to 118 matched controls of sedentary children. Girls had lower zinc levels than boys. Zinc was correlated to isometric adductor strength. Children with serum zinc levels less than 0.6 mg/L had lower insulin-like growth factor binding protein 3 than others. The authors conclude that zinc is lowered in trained adolescent gymnasts and even lower in females. This may play a role in abnormalities of puberty, growth and muscular performance. Adolescent gymnasts appear to be a population at risk for zinc deficiency. 22036 [exe, nut] Epidemiologic studies have shown an association between seafood consumption and the risk of thyroid cancer. Fish meals increase the serum concentrations of the long chain fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid for several days. This study evaluated 74 cases of thyroid cancer compared to 221 matched controls. The main finding was a significant inverse relationship between the sum of arachidonic acid and docosahexaenoic acid serum concentrations and thyroid cancer risk. A high eicosapentaenoic acid/arachidonic acid ratio, which indicates the consumption of fish fat, was not associated significantly with increased thyroid cancer risk. The data indicating the association between seafood ingestion and increased thyroid cancer risk many not be caused by fatty acids that come from marine animals. In conclusion, the data showed a protective effect of high serum levels of arachidonic acid and docosahexaenoic acid on the risk of developing thyroid cancer. High eicosapentaenoic acid/arachidonic acid levels which are associated with the consumption of fish fat and fish oils did not alter thyroid cancer risk. Further data is needed to show how these fatty acids inhibit thyroid cancer at a cellular level. 22417 [can] Twenty patients with long term sporadic Alzheimer's disease received vitamin supplementation of iron, B6 and coenzyme Q10. There was a significant improvement in a variety of mental and functional tests at one year. It is believed that coenzyme Q10 might reduce the free radicals formed by iron, and that B6 plays a role in neurotransmitter synthesis. The combination of these 3 may have a positive effect on reducing the signs and symptoms of Alzheimer's disease. 21436 [ger, neu, nut, psy] This study evaluated the effect of 30 gm of alcohol for 3 menstrual cycles compared to 3 alcohol free cycles on plasma carotenoid concentrations in 18 nonsmoking premenopausal women over a 6 month period. During the alcohol phase of this study plasma alpha and beta-carotene concentrations were significantly higher by 19% and 13%, respectively. The paired difference in mean plasma lutein/zeaxanthin concentration was significantly lower by 17% when the participants consumed alcohol than when they did not. This study is the first to document in women an independent effect of alcohol on plasma carotenoid concentrations without the potential interaction of smoking under controlled dietary conditions. 22752 [nut] Vitamin E succinate which is a derivative of natural vitamin E can inhibit the proliferation of several types of cells in culture. The antiproliferative properties of vitamin E succinate appear to be unique to this particular tocopherol compound since RRR-alpha-tocopherol, RRR-alpha-tocopherol acetate, and all-race- à-tocopherol do not inhibit antiproliferative properties in most cell culture systems. Studies suggest that vitamin E succinate's antiproliferative effects are unique to this form of vitamin E and appear to not involve antioxidant effects. There is evidence that vitamin E succinate may activate transforming growth factor TGF-beta growth-inhibitory signaling system. 22990 [nut] This study evaluated 96 cases of nasal cancer compared to 378 controls. There was a significant increased risk with an odds ratio of 6.8 of sinonasal cancer found in those employed in the whole leather industry. There was an odds ratio of 8.3 when associated with shoe making and leather tanning. This report was based on 110 patients who were accepted in some Italian hospitals during the last 3 years. Twenty-six cases had worked in the leather industry. Adenocarcinoma was the most frequent type of cancer observed. Chromium salts and natural tannins are possible aetiological agents. Nasal cancer in leather workers appears to affect many of those exposed to dust in the preparation of finishing of the heels and soles, which are in many countries tanned with vegetable extracts including extracts of wood. With regards to shoe manufacturing and repair, the leather dusts in tannins are mostly suspected. 22808 [can] Sexual functioning after myocardial infarction is rarely discussed by physicians. Even with instructions more than one-fourth of previously sexually active individuals fail to resume intercourse after a coronary event. Those who had a healthy sexual relationship before the heart attack have a much better chance for full recovery of sexual activity. Most of the patients are physically able to resume intercourse after a coronary event, but many have unnecessary fears that interfere with their activity. Some may be reluctant to mention their fears to the physician. As far as medical management, when a patient can walk 5 level blocks comfortably or climb 2 flights of stairs they can safely resume sexual intercourse. Before intercourse, agents such as beta blockers, calcium channel antagonists or nitrates can be taken. In the past, postcoronary patients were told to assume a "passive position and role" during intercourse because this was believed to put less burden on the heart. Extensive research has not confirmed this assumption. In these studies heart rate and blood pressure readings were actually higher when a patient assumed a new position. Thus it is not necessary for couples to change to an unfamiliar position. If the patient complains of chest pain in a certain position he should be instructed to take medication before intercourse or to avoid that position. Masturbation frequently occurs in the hospital the day after a coronary event, many times for psychological reinforcements of the individual's "manhood". It could be potentially dangerous during the first 72 hours after a myocardial infarction. Masturbation should be avoided until one is out of the high risk period for arrhythmias. 21578 [car, gu, gyn] This study, on 2 occasions, evaluated 12 kidney transplant patients with stable cyclosporine trough levels and received grapefruit juice or water every 3 hours for a period of 30 hours. Grapefruit juice increased the peak concentration of cyclosporine by 185 ng/ml. The ratio in the curve of metabolites of cyclosporin related to the inner end of the curve of cyclosporin was reduced by .137 on the grapefruit day. After grapefruit juice there was no other changes seen. The authors conclude that grapefruit juice inhibits the metabolism of cyclosporine for a brief period after administration which may explain why the inhibition of cytochrome P450 enzymes in the gut wall and, to a lesser extent by inhibited of these enzymes in the liver. Grapefruit juice can be a factor in the pharmacokinetics of cyclosporine. 22167 [nep, tran] This is a review article of 13 studies utilizing a meta-analysis technique on the relative risk estimate for breast cancer mortality for women age 50 to 74 years of age who underwent screening mammography compared to those who did not. The relative risk was .74. None of the summary relative risk estimates for women ages 40 to 49 years were significantly less than 1.0 irrespective of screening intervention or duration of follow-up. Screening mammography significantly reduced breast cancer mortality in women between 50 and 74 years of age after 7 to 9 years of follow-up regardless of the screening interval or number of mammographic views seen. There was no reduction in breast cancer mortality in women age 40 to 49 years of age after 7 to 9 years of follow-up. Screening mammography may be effective in reducing breast cancer mortality in the 40-to-49 age group after 10 to 12 years of follow-up, but this same benefit could probably be achieved by beginning screening at menopause or at age 50. 21643 [can] In septic shock there is an accumulation and enhancement in polymorphonuclear leukocytes, enhanced prostaglandin metabolism and tissue hypoxia which leads to a high concentration of oxygen radicals and their metabolites. There is also excessive high concentrations of nitric oxide in sepsis. High concentrations of nitric oxide cause the typical macro and microcirculatory problems normally seen in sepsis. Both nitric oxide and oxygen radicals are seen in early phases of sepsis and appear to influence the course of the illness. Oxygen scavenger therapy or inhibition of nitric oxide synthetase are promising approaches. It is not known the extent to which oxygen radicals and nitric oxide react with each other, thereby possibly potentiating their effects. Further research is needed. 22450 [met] A survey of 52.5 hours of children's Saturday morning television from 5 major networks recorded 997 commercials selling a product and 68 public service announcements. Of 564 food advertisements, 43% advertised foods classified in the fats, oils and sweets food groups. The most frequently advertised product was high sugar cereals. Commercials broadcast during children's Saturday morning programming promoted foods predominantly high in fat and sugar, many of which are of low nutritional value. In conclusion the foods that are advertised on Saturday morning television are the opposite of what is recommended for healthful eating for children. The authors believe it is important to address the issue of the commercialization of children's television and the effect of television food advertising on children's diet on a national level. 21597 [nut] Male guinea pigs were given low, medium and high vitamin C concentrated diets. Heart vitamin C was strongly dependent on dietary vitamin C; heart vitamin E showed a trend to increase as a function of vitamin C level in the diet. The low vitamin C diet decreased body weight gain, food intake and heart malondialdehyde without changing lipid peroxidation; whereas the high vitamin C intake increased oxidized glutathione and glutathione peroxidase and decreased body growth. A tendency to show higher levels of all the first line antioxidants (reduced glutathione, uric acid, superoxide dismutase, catalase and glutathione peroxidase) at either extreme high or low dietary levels of vitamin C was observed. The guinea pig heart showed capacity for enzymatic but not for nonenzymatic in vitro lipid peroxidation. The authors conclude that dietary vitamin C is able to increase the global antioxidant capacity of the heart tissue. 22005 [car] In evaluating 226 smoking mothers who were pregnant they were noted to have lower vitamin C concentrations in their blood streams compared to 174 nonsmoking participants. It was noted that their fetuses also received less vitamin C. It appears that smokers may need more vitamin C, and, maybe, more of other nutrients that have yet to be identified to get the appropriate amount of nutrients across the placenta to the fetus. The National Research Council included 2/3rds more vitamin C for smokers in its 1989 Recommended Daily Allowance Guidelines. These guidelines did not address the needs of pregnant smokers. On the average smokers had 15% less vitamin C than nonsmokers in their bloodstream. It is noted that smokers consume 30% more vitamin C. It appears that they have a biological craving to consume vitamin C containing foods and juices. This was stated because the smokers did not know that smoking specifically depletes vitamin C. Typically, newborns have twice the vitamin C concentrations of their mothers. Newborns of smokers had only 1.5 times as much as their mothers. This is not just a case of less available vitamin C but a probable transport problem of vitamin C across the placenta. Smoking mothers may need twice as much vitamin C as nonsmokers. The phase of delivery where the uterus expels the placenta takes nearly twice as long for smokers than nonsmokers. This is dangerous because the longer that this stage occurs the more likely hemorrhage may occur. The authors plan to study whether low vitamin C, which plays a role in connective tissue development, lengthens the final stage of labor. 22586 [obs, ped] In a dog model 18 animals were treated with magnesium sulfate soon after coronary occlusion while another 18 remained as controls. The treatment determined only slight reductions in heart rate and arterial blood pressure from the beginning to the end of the experiment. The necrosis was noticed in 63.7% and 44.2% of the risk area in the control and treated groups, respectively. The authors conclude that the magnesium treatment protected the ischemic-reperfused myocardium reducing the final necrosis of the risk area by 30%. The treatment suggests that magnesium in doses which cause minimal hemodynamic changes has a protective effect on the dog myocardium with respect to ischemia following reperfusion. 22763 [car] This study evaluated 8 healthy volunteers who were dehydrated by approximately 2% of their body mass by intermittent cycle exercise. Over a 30-minute period after exercise, the subjects ingested 1 of 4 drinks of a volume equivalent to their body mass loss. Drink A contained 90 mmol/l of Glucose; drink B contained 60 mmol/l sodium chloride; drink C contained 25 mmol/l potassium chloride; and drink D contained 90 mmol/l glucose, 60 mmol/l sodium chloride and 25 mmol/l potassium chloride. The treatment order was randomized. Urine output was greater after ingestion of the drink which contained the 90 mmol/l glucose solution alone than any of the other drinks. On the morning after the trial, the subjects who consumed the glucose-containing solution were in greater negative fluid balance than those who consumed the other 3 drinks. Urine osmolality was lowest after the ingestion of the glucose containing drink. On the morning after the test those test subjects were in greater negative sodium balance after the glucose and potassium chloride trials than after the sodium chloride and combination trials respectively. Negative potassium balance was greater after the glucose and sodium chloride trials than after the potassium chloride and combination trial. Chloride balance was positive after the combination drink and a smaller negative balance was observed after the drink which contained sodium chloride alone and compared to glucose- or potassium chloride-containing drinks. These results suggest that there is better whole body water electrolyte balance resulting from ingestion of electrolyte containing drinks. There was no added effect in including both sodium and potassium. These results showed that rehydration after exercise-induced dehydration in the heat is more effectively achieved when electrolytes are added to the rehydration fluid. 21336 [exe] This article reviews how blood pressure can be elevated due to side effects of drugs, poisons and foods. A chart of chemically induced hypertension is given with many prescription medications, drugs, hormones, toxic elements being listed. Steroids can trigger hypertension. Other agents include contraceptives and estrogens, anabolic steroids, anesthetics, drugs directly activating the sympathetic nervous system, over-the-counter stimulants, monoamine oxidase inhibitors, antidepressive medications, alcohol, nicotine and nonsteroidal anti-inflammatory agents. Also noted is the rebound hypertension phenomenon in response to the withdrawal of antihypertensive medications. 21986 [car] This study evaluated 185 newborns and their mothers with tooth filling surfaces between 0 and 780 mm2. Mothers and newborns showed a highly significant correlation between the median value from .4 resp. .5 ug/Hg/L. The placenta has a retention capability up to 10 times higher mercury values and a low positive correlation to amalgam surfaces. There was no relationship between the blood values of the women and the children and the size and the surfaces of amalgam fillings. A high consumption of fish led to higher mercury values in umbilical cord blood even in mothers without amalgam fillings. Symptoms of diseases such as headaches, allergies and eczemas occurred in both those with and without amalgam fillings. All women gave birth to healthy children. The authors feel that some of the concerns regarding heavy metal contamination during pregnancy are not justified. 22706 [dent, gyn, ped] In a rat model it was found that melatonin administration caused a 2-fold rise in glutathione peroxidase activity in the brain within 30 minutes. It is noted that brain glutathione peroxidase activity is higher at night than during the day which correlates with high night time tissue melatonin levels. Glutathione peroxidase is thought to be the principal enzyme in eliminating peroxides in the brain. Glutathione peroxidase reduces the formation of hydroxyl radicals formed via the iron-catalyzed Fenton-type reactions from hydrogen peroxide by reducing this oxidant to water. The stimulation of brain glutathione peroxidase may be an important mechanism by which melatonin exerts its potent neuroprotective effects. 22579 [met, neu] In a study of 262 females, out of 3,405 consecutive women approximately 8% attending a maternity clinic were anti-thyroid microsomal antibody positive. Out of this group 71 were evaluated for thyroid-stimulating hormone-binding inhibitory immunoglobulin and thyroid stimulating antibodies in early pregnancy and continued serially until 6 months after delivery. Seven of 71 patients with who were antithyroid microsomal antibody positive had positive thyroid stimulating antibodies during their pregnancy. All showed some thyroid dysfunction during the postpartum period; 5 developed Gravesþ Disease - 2 had persistent disease and 3 had transient cases. None of the 64 thyroid stimulating antibody negative patients developed Gravesþ disease though 44 developed various types of thyroid dysfunction as a result of autoimmune thyroiditis. The authors conclude that a positive thyroid stimulating antibody test can help physicians find the 1 in 200 women at risk for postpartum onset of Gravesþ disease during their early pregnancy. 21375 [end] In the 1920s before anticonvulsant medications were available high fat diets were used to control seizures in epileptic children. Clinical trials are now confirming that this does work "better than any other regimen" according to Dr. John M. Freeman, the director of the Pediatric Epilepsy Clinic at Children's Center in Baltimore, Maryland. He recommends this diet for children who don't respond to anticonvulsants. It is a stringent diet consisting of high fat, low protein, low carbohydrate foods. No drug company is promoting this regimen as they do conventional antiepileptics, so this therapy is not well known. It is estimated by some experts that this diet can lead to a reduction of seizures in 50 to 70%of the children, which few drugs can claim. According to Dr. Freeman the concern about the diet elevating cholesterol levels is not warranted. Dr. Freeman states, þAssume the diet is atherogenic. It is still better than poisoning a child's brain for 10 years.þ Giving a pill is much easier than putting a child on a strict diet. Patients initially should be hospitalized to ensure that the metabolic processes derived from the diet will be initiated. In 1 neurologist's experience, one third of the children who start the diet don't tolerate it. Side effects include diarrhea and dehydration. A sample diet for 2 days includes: Breakfast of scrambled eggs, butter, diluted cream, orange juice. Lunch: Lettuce leaf with mayonnaise, spaghetti, squash with butter and Parmesan cheese, orange diet soda mixed with whipped cream. Dinner: Asparagus with butter, chopped lettuce with mayonnaise, hot dog slices with ketchup and vanilla cream popsicle. Day 2, breakfast: Bacon, melon slices, scrambled eggs with butter and a vanilla cream shake. Lunch: Celery and cucumber sticks, tuna with mayonnaise and sugarless jello with whipped cream. Dinner: Chopped lettuce with mayonnaise, broiled chicken breasts and a cinnamon apple slice with butter topped with vanilla ice cream. The ratio of fats to protein and carbohydrates combined is 4:1 for children starting out on the diet; it can usually be lowered to 3:1 after the first year. The ketogenic diet allows children three fourths of the recommended daily allowances of calories for their ideal body weight. Even things like toothpaste need to be taken into consideration with regards to calories. Dr. John M. Freeman has written a book entitled, The Epilepsy Diet Treatment: An Introduction to the Ketogenic Diet, by Demos Publications 1994 of New York. 21550 [neu] Twenty-five hundred babies are born with neural tube defects each year or 1 or 2 per 1,000 births. Many of these may also be spontaneously aborted. Anencephaly and spina bifida are the most common neural tube defects which occur in about equal frequency while encephaloceles are much rarer. Anencephaly is usually fatal before or shortly after birth while spina bifida is compatible with life though they are moderately to severely handicapped and sometimes have mental retardation. Neural tube defects occur within 1 month of conception and over 90% occur in women without a prior family history of the disorder. Published reports have noted that the incidence of neural tube defects can be reduced if folic acid is ingested prior to and through the first weeks of pregnancy. Dose ranges vary from .4 mg to 5 mg started at least 1 month prior to the conception and continue through the first month of trimester. If women continue to ingest .4 mg of folic acid each day through their reproductive lives either alone or a multivitamin preparation a daily intake of .6 of the total of folates is likely. This is probably enough to result in a substantial reduction of neural tube defects. The average diet provides about .2 mg of dietary folate per day. One can get their folic acid from food but it is noted that food folates are less well absorbed than synthetic folates. Fortification of staple foodstuff with folic acid is potentially an effective and inexpensive approach to assisting women with their intake of folic acid. The recommendation for combination of dietary folates and folic acid supplementation is unlikely to exceed .8 mg per day. The American College of Medical Genetics recommends the following: 1. Women should be advised to supplement their diets with .4 mg per day of folic acid throughout the reproductive years. 2. That the Food and Drug Administration should require that enriched cereal grain flowers are fortified with folic acid. 3. Women with a previous history of neural tube defects in their family should obtain genetic counseling concerning their risk of reoccurrence, the management of subsequent pregnancies and the appropriate folic acid intake for them. 22246 [gen, pre] In the adult 6 to 8 gm of S-adenosylmethionine (SAM) is produced daily. Most of it is produced in the liver where it is utilized. The methionine cycle and trans-sulfuration pathways are impaired in human liver disease. One or more of these abnormalities may be responsible for some of the clinical manifestations of liver cirrhosis. The increased breakdown in methionine at the expense of methylation reactions is generated by a need to synthesize hepatic GSH to offset the damaging oxidant effects of ethanol. Paracetamol (acetaminophen) can result in fetal liver damage in overdosed individuals. Two forms of cytochrome P450 convert paracetamol into a reactive metabolite that depletes liver reduced glutathione. Reduced glutathione is a tripeptide containing glycine, glutamic acid and cysteine. It is the most important cellular thiol. N- acetylcysteine, in an hepatic toxic condition resulting from paracetamol overdose can, if given in time, improve survival and reduce liver damage. Different studies have shown SAM to be effective in symptomatic treatment of intrahepatic cholestasis of the liver and of pregnancy. SAM has also been reported to improve liver function in various chronic liver diseases including alcoholic and nonalcoholic cirrhosis. This article also notes that the trans-sulfuration pathway, which can lead to homocystinuria/homocysteinemia, is dependent on enzymes that are cofactors with vitamin B12, folic acid, B6, choline and betaine hydrochloride. Homocysteine is believed to be an independent risk factor for the development of coronary artery disease in man. The molecular basis for homocysteine playing a role in cardiovascular function is not known, but it may be related to its interference with cross-linking of collagen. 21395 [car, hep] This is an extensive review article on the role of alcohol in cancer. Alcohol intake appears not to increase the risk of cancer of the lung, bladder, prostate, stomach, ovary, endometrium or melanoma. Alcohol may be a weak causal factor for pancreatic cancer. Alcohol consumption continues to increase the risk for cancer to the mouth, pharynx, larynx, esophagus and liver. The effect of alcohol consumption on cancer of the breast and the large bowel is not clear. 22106 [can] The Certification Board for Nutrition Specialists which was founded by the American College of Nutrition is offering licensing as a certified nutrition specialist for professionals holding advanced degrees from regionally accredited universities. The Board has scheduled its first examination on October 13, 1995 in Washington, D.C.. For more information you may contact the Board at (212)332- 0774. 22355 [nut] This study evaluated 76 patients during lumbar disc surgery for the calcium/magnesium ratio in the fibrous connective tissue from the ligamenta flava. The calcium/magnesium ratio was almost constant through all age groups. It was concluded that the constancy of the calcium/magnesium ratio throughout the lifetime is an integral quality of elastic fibers which may be explained by the long biological half-life of elastin. Magnesium plays a crucial role in connective fibers with elastic properties. Comparing elastic tissues with non-elastic tissues, with increasing elasticity, a magnesium/calcium ratio in favor of magnesium was found. The calcium/magnesium ratio was almost the same in patients with lumbar disc prolapse and with autoptic material from patients without herniated disks. Disk herniation through sclerotic or even ossified annulus fibrosus may be perceived as extreme aging of collagen. The biological half-life of uninjured elastin, the essential component of elastic fibers of ligamenta flava, is close to the lifetime of man. The authors conclude that the unexpected finding of a virtually unchanged calcium/magnesium ratio in ligamenta flava may be explained by the special biological behavior of elastin. 21785 [neu, ort] This study evaluated 200 white, African-American, Hispanic and Asian parents of infants who died of SIDS between 1989 and 1992 compared to 200 control parents who delivered healthy infants. Conditional logistic regression resulted in overall adjusted odds ratios for SIDS associated with passive smoking from the mother of 2.28, the father of 3.46, other live-in adults of 2.18 and all sources of smoke of 3.50. A dose-response effect was noted for SIDS associated with increasing number of cigarettes as well as the total number of smokers. Breast feeding was protective for SIDS among nonsmokers when adjusted for potential variables. Passive smoking in the same room as the infant increases the risk for SIDS. This fact should be shared by physicians with their patients who are new or prospective parents. 21965 [ped] This doctor notes that he has kidney stone patients sit in a hot tub of nonscalding water for 20 to 30 minutes. This will give them temporary relief. 21980 [uro] This study evaluated perchloroethylene exposure in 28 dry cleaning businesses and in 25 homes occupied by dry cleaners in a town in Italy. The amount of perchloroethylene on the dry-cleaning premises varied from establishment to establishment. Perchloroethylene in alveolar air samples collected at the end of a work day correlated closely with the 8-hour time weighted average values and with alveolar air samples collected at home in the evening and the following morning. The authors discovered that perchloroethylene levels inside the homes of dry-cleaners were significantly higher than in the 29 homes selected as controls. The perchloroethylene alveolar samples collected at home suggests nonoccupational exposure to perchloroethylene for family members of dry cleaners. Little is known about the effect of chronic exposure to perchloroethylene on health, though at low doses it is suspected of being a carcinogen. It is advisable to reduce the risk of perchloroethylene exposure in the general population, particularly when obvious sources of contamination are known. 21719 [can, env, pul] Ginkgolide B is a potent inhibitor of platelet activating factor. This was a randomized, double-blind, placebo-controlled trial in 104 patients who for 7 days 43 received a placebo, 29 received 240 mg per day of Ginkgolide B and 32 received 360 mg per day of Ginkgolide B. There was no statistical difference between the 3 groups for changes in rankin, kurtzke expanded disability status scale and hauser ambulation index scores. There was a trend in favor of the groups treated with Ginkgolide for a change of the Rankin AI scores. The authors conclude that Ginkgolide B is not an effective treatment of exacerbations of multiple sclerosis. Exacerbations of multiple sclerosis are associated with inflammation, white cell passage into the central nervous system and damage to the blood brain barrier. This damage is shown consistently on CT and MRI scans with contrast enhancement. Steroids are supposed to repair the blood brain barrier. Platelet activating factor is an important mediator of inflammation as a pivotal role in the vascular stage in the inflammatory process. Experimental studies have shown that Ginkgolide B is a compound that is a potent inhibitor of platelet activating factor and has been shown to prevent and treat experimental allergic encephalomyelitis, a widely used model of inflammatory demyelination that mimics the exacerbations of multiple sclerosis. The authors conclude that intravenous steroid courses are the only established effective treatment for acute exacerbation of multiple sclerosis. 22085 [neu] In this review article it is concluded that intestinal dysmotility can result in bacterial overgrowth. Bacterial overgrowth may have an effect on digestion and absorption. Bacterial overgrowth may occur in patients with late radiation enteropathy. There is also a possibility that the bacterial overgrowth occurred first even though it is less likely. 22509 [gas] Genuine food intolerance can be due to a variety of mechanisms which include enzyme deficiency, pharmacological reaction, a toxic effect or, an immunologic reaction would be more specifically classified as a food allergy. The relationship to food and behavior is a noteworthy topic among the news media. Foods can have pharmacological effects. Caffeine for example in coffee and other foods can increase wakefulness and concentration but can also cause irritability. The peptides in milk and wheat have exorphin-like activity. Amino acids such as tryptophan in foods are the precursor to vaso-active mediators such as serotonin and can act as precursors for neurotransmitters. Food containing high concentrations of these amino acids may affect behavior, mood and appetite. Foods high in certain additives such as tartrazine have been shown to effect basophil's histamine release. It is not surprising that a high food additive- containing diet might accentuate hyperactive behavior by direct pharmacologic mechanism. The standard for diagnosis of food intolerance is the double-blind food challenge. Few clinics have the experience or the time to devote to this "painstaking" diagnostic procedure. In 1 study of 104 patients with severe migraines 38% improvement on diet, 26 reacted on open challenge with food but only 15% had reproducible symptoms on double-blind challenge. In 1 study 59 of 78 children referred to a diet clinic with hyperactive behavior improved on a few food diet, 19 subsequently had a double-blind challenge with the offending foods and a crossover challenge and clear differences were seen in 14 children with significant difference between active and placebo challenges. Whether total exclusion of a food is necessary or whether only a reduction of the pharmacologically active ingredients to reduce the reaction to food and improve behavior is not known. It is also important to note that in behavior problems in children it is natural for a parent to be lead to the believe that a particular symptom is due to a food which is an extrinsic factor versus some other psychosocial reason. The author concludes by this quote: "There is an association between certain foods and hyperkinetic disorders, but only in the minority of affected children". Still much work is needed to define the association between behavior, food and dietary modification. Individuals with genuine food-associated behavior should be evaluated to identify the underlying pathophysiological mechanisms which might improve the diagnosis and management of this in the future. 22932 [all, psy] This Italian study of 755 cases of lung cancer compared to 755 controls showed that air pollution is a moderate risk factor for certain histologic types of lung cancer. Compared to those in a residential area, those in a rural area had a relative risk of .6. The relative risk was 1.5 for residents in the center of the city and 1.4 for residents in the center of industrial areas in Trieste, Italy. In the center of the city, the excess risk was almost completely related to small cell carcinoma and to large cell carcinoma. 22659 [can] This study evaluated 501 children between 1 to 5 years of age who were classified as exposed or nonexposed to environmental tobacco smoke with a cut off of 10 ng cotinine per mg creatinine in the urine. Exposed children were 3.5 times more likely to have increased respiratory morbidity than nonexposed children after adjusting for variables. Respiratory morbidity was defined as 3 or more episodes during the previous 12 months. The authors concluded that environmental tobacco smoke is an important preventable cause of early childhood respiratory morbidity. 22960 [pal, ped] This is a case report of a 6-year-old who was admitted to the hospital with acute gastroenteritis. On physical examination, she was found to have a lesion about 2.5 cm in diameter on her left foot similar to a 3rd degree burn. The lesion healed in approximately 32 days without leaving any scar. It was discovered that the childþs grandmother had placed crushed garlic cloves under a bandage over the effected area for 2 days prior to admission as a remedy for a minor erosion caused by the shoe. The author notes that in addition to this case report there are only 2 other reports of garlic burns. One case was the development of a second degree burn in a 17-month-old after a garlic petroleum jelly plaster had been applied to the skin of both feet for approximately 8 hours. The lesions healed in 2 weeks with topical medication. In another case, a similar second degree chemical burn occurred in a 6-month- old boy; crushed garlic cloves had been applied on both wrists for 6 hours. These burns healed within a 6 week period. It has been suggested that the same factors which cause allergic dermatitis with garlic contact are also the same substances which may produce the burn. These may be diallyldisulphide, allylpropyldisulphide and allicin. 21647 [der, nut, tra] Under normal circumstances very little protein is metabolized to provide energy for muscle contraction. At rest or low exercise intensity the metabolism of fat provides a considerable portion of energy for resting metabolic processes and muscle contraction. At high intensity exercises the metabolism of bodily carbohydrate, which is blood glucose and liver and muscle glycogen, provides the predominant fuel for muscle contraction. Fatigue occurs when these substrates reach low amounts. For training on a daily basis and over the long term, consumption of a diet containing 10 gm of carbohydrate per kg body weight per day as foods or foods combined with glucose, sucrose or glucose polymers maintain higher muscle glycogen concentration than does a diet of 5 gm of carbohydrate per kg body weight per day. A consumption of food with a higher moderate glycemic index may produce greater muscle glycogen synthesis than do foods with a low glycemic index, although this data has not been totally clarified. The feeding of glucose, sucrose or glucose polymers of 4 to 5 gm per kg body weight 3 to 4 hours before and 1 to 2 gm per kg body weight 1 hour before endurance exercise will maintain or elevate blood glucose, enhance carbohydrate oxidation and improve endurance performance. It is possible that the consumption of fructose as a pre-exercise carbohydrate feeding will improve performance. The consumption of glucose, sucrose or glucose polymers during exercise and before the decline in blood glucose will maintain blood glucose, elevate the rate of carbohydrate oxidation and dramatically improve endurance performance. Fructose can cause gastric distress but fructose feeding during exercise may influence carbohydrate oxidation and influence endurance performance. Glucose, sucrose or glucose polymer ingestion immediately and at 2 hour intervals after or as frequently as possible, up to 1.2 gm per kg body weight per hour, will produce the highest rates of muscle glycogen synthesis. Fructose feedings in similar amounts at similar time intervals will produce a 50% slower rate of muscle glycogen synthesis than will simple carbohydrates and glucose polymers. Chronic consumption of low carbohydrate foods will impair high intensity sprinting exercise. Ingestion of glucose, sucrose or glucose polymers during exercise may improve endurance capability for intermittent exercises such as soccer and ice hockey. 22766 [nut] This is an advertisement put out by Hoffman-LaRoche on the evidence regarding the potential benefits of antioxidants. Free radicals may oxidize LDL enhancing the atherosclerotic process. Ex vivo studies of LDL peroxidation show that the antioxidants vitamin E and beta-carotene neutralize free radicals and are consumed before LDL is oxidized. Vitamin C in solution increased the lag time by 10-fold between the start of the oxidation and the consumption of both vitamin E and beta-carotene. Vitamin C also significantly inhibits LDL oxidation in vitro and synergizes the antioxidant effect of vitamin E. Studies have shown protection against LDL oxidation was significantly increased with vitamin E supplementation. Large epidemiologic studies in Europe show a given serum cholesterol level is associated with significant interpopulation differences in the incidence of coronary heart disease. Recent data suggests substances other than dietary fat intake may affect coronary heart disease incidence. In Southern Europe as opposed to Northern Europe, there are higher amounts of fruits and vegetables consumed which contain high amounts of antioxidants; this high intake correlates with lower coronary heart disease incidence. Controlled intervention trials in antioxidants are being carried out worldwide. Preliminary results from a large scale ongoing study showed a reduced risk of coronary heart disease following 50 mg of beta-carotene on alternative days. However, a study of Finnish smokers did not confirm the epidemiologic observations on the protective roles of beta-carotene and vitamin E. To fulfill antioxidant needs, this ad suggests that everyone should continue to follow dietary guidelines endorsed by the USDA and the National Cancer Institute, which is consuming about 3 servings of fruits and 4 servings of vegetables daily. Less than 10% of Americans comply with these guidelines, leaving more than 90% of the population with a short fall of essential nutrients, including the antioxidant gap. The authors state, when appropriate, one should consider fortifying foods or taking dietary supplements containing vitamin C, E and beta-carotene. With regards to safety, the overall scientific evidence accumulated over many years supports the safety of vitamin C, E and beta-carotene even in reasonably elevated levels. The following epidemiologic studies are associated with high intakes of antioxidants reducing the risk of coronary heart disease: European populations cosponsored by the World Health Organization showed increased serum vitamin E and a decreased CAD incidence; The NHANES Study of over 11,000 individuals showed vitamin C from diet and supplements resulted in a reduction in cardiovascular mortality; The Nurses Health Study of over 87,000 females showed vitamin E supplements greater than 100 I.U. per day versus none showed a 40% risk reduction in coronary artery disease incidence; The Health Professional's Follow-up Study of over 39,000 males showed vitamin E supplements greater than or equal to 100 I.U. per day versus none showed a 37% reduced risk of coronary heart disease. Also, dietary beta-carotene showed a 70% coronary heart disease risk reduction in current smokers and 40% in former smokers; and the Euramic Study of over 1,400 males showed beta- carotene in adipose tissue concentrations and a reduced risk to myocardial infarction in current and former smokers. 21845 [car, nut] This commentary in support of natural family planning methods is considerably different than the "rhythm method" or the Roman Roulette approach. In a multi-center trial of the ovulation method of NFP that was undertaken between 1975 and 1979 one of the authors was a statistician. The main conclusions drawn from this study were that: A. Irrespective of cultural, educational, or economic background, over 95% of fertile women can, and are willing to, recognize the mucus signs of fertility; B. In this fertile group of women having regular intercourse without the use of barrier or chemical methods the fertility rate was 22.6 pregnancies per 100 women years; C. The preovulatory and postovulatory days designated by the ovulation method of NFP Rules as infertile were indeed infertile as the pregnancies in this phase were 4 per 1,000 acts of intercourse; and D. The designated fertile phase was indeed fertile, as intercourse during this phase resulted in conception with increasing frequency the nearer to ovulation the intercourse occurred which was 2 pregnancies for every 3 acts of intercourse on peak days of the mucus sign. The mucus changes to a more stretchy clear substance during the time of ovulation to enhance the viability of the sperm. The authors reviewed total pregnancy rates of natural family planning studies conducted in the 1990s which included broad spectrum of cultures. Three studies with results greater than 5 were all trials of atypical NFP approaches or teaching methods. The results can be compared with reported pregnancy rates of between .18 and 3.6 for artificial contraceptive methods in well motivated couples. NFP is the only method that empowers a couple to control their own fertility irrespective of economic status and independently of distributors of pills and condoms. Natural family planning allows couples to avoid or achieve pregnancy. Those wishing to achieve pregnancy will have extremely high pregnancy rates while those strongly motivated to avoid pregnancy will have extremely low pregnancy rates. A criticism of natural family planning is that the periods of abstinence are detrimental to the marital relationship and the family. It has not turned out since the advent of oral contraceptives that marriages, families, couples and children have benefit. It is noted that at the same time the pill has been around there has been a massive increase in marital and family breakdown. This is not a proven link, but some believe that the availability of uninterrupted sexual intercourse is something that is an unrealistic expectation in marriage and sets the course for the breakdown of marriage. NFP takes understanding and cooperation between the 2 married parties. There needs to be mutual discipline in NFP which can foster marital harmony and enhance relationship. Women note that in the times of avoidance of sexual intercourse there can be an enhanced expression of non-genital physical love which is something that has been longed for and helps their sexual responsiveness. The authors have suggested that there is a monthly honeymoon period which occurs at the resumption after the fertile phase enhances the sexual relationship. Some feel that natural family planning might be a partial solution to the sexual revolution of the last 20 or 30 years which has caused in some individuals, marital and family breakdown on a massive scale and at a vast cost. The authors feel that those who are concerned about the rights of women worldwide should be concerned about why they are not being informed of the symptoms of ovulation which are so easily and universally recognizable. Women are fertile no more than 6 to 8 days in the cycle. These easily recognizable signs should empower women to control their fertility. Many females are dissatisfied with artificial contraceptive methods and do not know of the natural family planning alternative. Many subfertile women who desperately want to achieve conception are not being given this basic information that would enhance their chances. The author feels if one looks at this from an ecological feminist, economic family or just plain common sense point of view all women are entitled to this information. 22901 [end, gyn] The effects of Norepinephrine at 4 ug/kg, isoproterenol at 10 ug/kg and phenylephrine at 20 ug/kg were evaluated in an anesthetized dog model with normal plasma magnesium and induced hypermagnesemia. Norepinephrine caused a 24% increase in heart rate and a 103% increase in systemic vascular resistance in normo-magnesemic dogs while the hypermagnesemic dogs had values of 13% and 1%, respectively. Isoproterenol increased the heart rate by 48% and 18% in dogs with normo and hypermagnesemia, respectively. Phenylephrine increased the systemic vascular resistance index by 74% only in the normomagnesemic state. The effects of the drugs were significantly different without and with the simultaneous administration of magnesium sulfate resulting with plasma levels of 1.3 mEq/l and 6.8 mEq/l, respectively. The authors conclude that acute induced hypermagnesemia antagonizes circulatory effects of adrenergic stimulation which may explain the antiarrhythmic and hemodynamic effects during acute myocardial ischemia. 22762 [car, end] This doctor notes that he has kidney stone patients sit in a hot tub of nonscalding water for 20 to 30 minutes. This will give them temporary relief. 21980 [uro] This article reviews 4 different case reports of inflammatory dermatitis and in each case there was clearing of this previous recalcitrant dermatosis accompanied by psychiatric improvement. The authors conclude that insight-oriented psychotherapy may provide long lasting cutaneous improvement and improve life adjustment and psychologic well being in some cases or recalcitrant inflammatory dermatoses. 22470 [der, psy] This is an editorial on the study by Selhub and colleagues in the February 2, 1995;332 issue of The New England Journal of Medicine. The article suggests that elevated levels of blood homocysteine increase the risk of cardiovascular disease. Consistent findings have emerged from more than 20 case-control and cross-sectional studies of over 2,000 subjects indicating that patients with stroke and other cardiovascular diseases tend to have higher levels of homocysteine than those without the disease even though most have values within the normal range. In the Physician's Health Study, the 271 men who later had myocardial infarctions had significantly higher mean base-line levels of homocysteine than matched controls who were free of infarction. Men whose homocysteine levels were in the highest 5 percent had three times the risk of myocardial infarction than those with lower levels, even after adjustment for coronary risk factors. The prevalence of carotid-artery stenosis has been shown to be related to increasing plasma levels of homocysteine. One hypothesis regarding homocysteine's effects on cardiovascular disease is that damage stems from a toxic effect by homocysteine on vascular endothelium, which impairs the production of endothelium-derived relaxing factor. Homocysteine may stimulate the proliferation of smooth muscle cells, which is part of atherogenesis. Homocysteine can also act as a thrombogenic agent. The most dramatic elevations of homocysteine, which lead to life threatening vascular abnormalities at a young age, are due to an enzyme defect. Inadequate folic acid intake is the main determinant of homocysteine-related increase in carotid- artery thickening. Folic acid, vitamins B6 and B12, all play an important role in homocysteine metabolism. Homocysteine levels reach a stable low level only when folic acid intakes of approximately 400 ug per day or more are sustained. Folic acid supplements in the range of 1 to 2 mg per day are generally innocuous, and usually are sufficient to reduce or normalize high homocysteine levels, even if the elevation is not due to inadequate folic acid supplementation. When folic acid consumption is high the minor and common genetic variances have no clinical significance. But when folic consumption is marginal the risk may be elevated. In the Physician's Health Study, 5 percent of the controls had plasma homocysteine levels above 15.8 umol/L, the level which is associated with a three-fold increased risk of myocardial infarction. In the older and less highly selected population of the Framingham Heart Study, 21 percent had high levels of homocysteine. The author notes, "Because the weight of evidence is substantial and the intervention appears to be benign, it may be possible to make broad preliminary recommendations based on trials of secondary prevention or disease progression rather than wait for large, expensive and prolonged trials of primary prevention. In the meantime, it will be prudent to ensure adequate dietary intake of folate". 21740 [car] This study compared 1,768 women with breast cancer to 13,905 controls, most of whom were below 55 years of age. The relative risk of breast cancer for women who had ever used depot medroxyprogesterone was 1.1. There was no increased risk with the increasing duration of depot medroxyprogesterone use but the relative risk estimates were higher in certain subgroups of women. Women who had started using depot medroxyprogesterone within the previous 5 years were estimated to have a relative risk of 2.0. The increased risk of breast cancer seen in users could be due to enhanced detection of breast tumors in women using depot medroxyprogesterone or to the acceleration of the growth of pre-existing tumors. Women who had used depot medroxyprogesterone more than 5 years previously had no increased risk of breast cancer regardless of the duration of use. Depot medroxyprogesterone acetate has been now approved for marketing as a contraceptive agent in the United States even though there are still some unresolved issues regarding its relationship to the risk to breast cancer. 21962 [can] In a rat model induced glomerulonephritis in a study utilizing a diet that was normal in protein intake yet restricted in L- arginine. This resulted in decreased protein, decreased expression of TGF-B1, messenger RNA and TGF-B1 protein and decrease the production and deposition of matrix components. L-arginine, not D- arginine supplementation to low protein diets reversed this effect. This data suggests arginine is a key component in the beneficial effects of a low protein diet. 22843 [nep, nut] This article reviews the nutritional requirements when the body is faced with environmental and physical stress. Metabolic adaptations to heat, cold and high altitude exposure can result in alterations in nutrient requirements. Energy expenditure is increased in all 3 of the above categories. B vitamin cofactor requirements increase in proportion to energy expenditure due to oxidation of fat and carbohydrate. Increased B vitamin nutrient requirements are usually met by an increasing dietary intake to meet energy needs. Nutrients such as iron may be required in greater amounts to meet the altitude-induced hematopoietic response in females. Additional quantities of vitamins and minerals with antioxidant properties may be beneficial to reduce the increased oxidative stress that is associated with heat, cold or high altitude environments. Women and men working in severe environments may benefit from supplemental antioxidant nutrients, such as vitamins E, C, beta- carotene, selenium, copper, zinc and manganese, to reduce lipid peroxidation and protein and DNA damage. Reflected sunlight from ice, snow or sand, cloudless skies of the desert and high elevations and the rarefied air of high altitude can contribute to the solar load and associated photobiologic effects. These effects, in combination with enhanced aerobic metabolism from increased energy expenditure, result in increased potential for generating reactive oxygen species which may result in the damage of lipid components of membranes, enzyme proteins and DNA. Supplemental antioxidants and/or foods rich in antioxidant nutrients may be valuable during periods of prolonged work and recreation in extreme outdoor environments. 21946 [env, exe, nut] Exercise should be the prescription for osteoarthritis. The goal is to use a lot fewer nonsteroidal antiinflammatory agents and a lot more exercise. The Arthritis Foundation states that physical therapy may be the most valuable treatment for the estimated 16 million people in the United States who have osteoarthritis. Physicians should prescribe a low impact exercise program involving keeping the joints flexible, preserving the strength of the muscles on which the joints depend for their stability and protecting diseased joints against further damaging stresses. Exercise also requires the patient to take charge of their therapy. It is noted that exercise is one of the prescriptions that doctors feel most uncomfortable writing. In a study of 110 elderly patients with osteoarthritis of the knee and/or hip fewer than 48% had received medical advice to exercise and very few had received enough exercise related teaching in Arthritis Care and Research, 1992;5:36-41. It is noted that the Arthritis Foundation has 70 chapters in the United States and sponsors a series of exercise programs. You can call the foundation at 1 (800) 283- 7800 to determine where to send your patients if you are a physician. Chapters have monthly classes. Those with osteoarthritis may benefit by doing exercise in the morning. Trying to get 10 repetitions is beneficial but if the pain persists they can go down to 5 repetitions. If they have no pain they should work towards 20 repetitions. One study of 102 patients with documented primary osteoarthritis of one or both knees showed that exercising patients decreased medication use when compared to nonexercising individuals. This was in the Annals of Internal Medicine, 1992;116:529-534. Reducing the dose of nonsteroidal anti-inflammatory agents reduces the level of risk to gastrointestinal side effects. One study showed that the rate of gastrointestinal bleeding was 52% in patients receiving 2 nonsteroidal anti-inflammatory agents and 23% of those receiving 1. High dose nonsteroidals have not been shown to change the course of the disease. It is not clear that the joint pain is due to synovitis. The general cost of nonsteroidal antiinflammatory agents in comparison with acetaminophen is generally greater with more significant side effects. It is reasonable to consider acetaminophen as a first line therapy in the symptomatic management of patients with osteoarthritis. Side effects of nonsteroidals include gastropathy, renal insufficiency and neurologic complications are the most common in elderly patients. The annual rate of hospitalizations for peptic ulcer disease among elderly patients taking antiinflammatory doses of nonsteroidal anti-inflammatory agents is nearly 7 in 100, about 4 times the rate for elderly not on nonsteroidals. Also 30% of hospitalizations and deaths related to peptic ulcer disease are attributed to nonsteroidal antiinflammatory drugs (Annals of Internal Medicine, 1991;114:257-263). The higher cost of nonsteroidal anti-inflammatory agents is also changing prescription practices. Managed care is changing around prescription practices where almost a decade ago nonsteroidals were the initial prescription for osteoarthritis in nearly 6 million physicians. 21896 [ort, rhe] This study evaluated, in a placebo-controlled, double-blind study, 33 patients with chronic peripheral arterial occlusive disease who carried out a physical training program 3 times a week for 24 weeks. During this time they were given 160 mg/d of Ginkgo biloba extract-EGb 761 or a placebo. The incidence of pain-free walking was higher with Ginkgo biloba extract than with the placebo. The difference was statistically significant. 21662 [car] This is a commentary on the role of the International Physicians for the prevention of nuclear war and their work since the 1980s and the current situation with regards to nuclear weaponry and the threat of war. From a very small start the International Physicians for the Prevention of Nuclear War grew to 200,000 members in nearly 80 countries. In its brief existence it helped persuade millions of people to confront for the first time the reality of nuclear war. The International Physicians for Prevention of Nuclear War began with the meeting of 3 U.S. and 3 Soviet Physicians in Geneva, Switzerland in December 1980. The Soviet participants were doctors Eugene Chazov, Mikhail Kuzin and Leonid Llyin. An historic telecast in 1982 broadcast, on prime time, on the Soviet first channel and transmitted to 12 time zones, was watched by more than 100 million people. There was a graphic description given and how such a war would reduce the Soviet Union to look like moonscape. The shallows of nuclear war will not be eliminated without public education, arousal, and involvement. Politicians do not respond to the insistent calling of history. They rise to the challenge only when a powerful public opinion clamors for change. The authors believe that physician involvement is critical to help resolve a number of crucial global issues of which none is greater than achieving the abolition of nuclear weapons. 22963 [med, rad] Endurance exercise events are often between 6 and 24 hours in duration, and can even extend over several days. Ultra endurance athletes train from 1 to 6 hours per day and multiple training sessions during a single day are not uncommon, especially for triathletes. Some ultra endurance athletes may have to participate in 24 hour races to prepare or qualify for other events. Cyclists tend to have higher energy intakes than runners or triathletes. Endurance athletes have been known to expend 1,000 to 3,000 kcals of energy during training. To maintain glycogen stores ultra endurance athletes should consume 6 to 10 gm of carbohydrate per kg of body weight each day or get approximately 60 to 70% of their total calories from carbohydrates. This can be accomplished by frequent snacking of high carbohydrate foods. Though protein requirements of ultra endurance athletes have not been evaluated critically, there is evidence that protein needs of endurance athletes may depend on the intensity and volume of their training. A protein intake of 1.6 gm per kg is the estimate that has been given to maintain nitrogen balance in the endurance athlete. In general protein needs can be met if 12 to 15% of the energy intake is from protein. Water, carbohydrate beverages, diluted fruit juices or sodas are recommended for fluid replacement. The carbohydrate content should not exceed 12%; 6% to 8% solutions are optimal. Drinking water before a long training session is recommended but excessive water intake during exercise may lead to electrolyte imbalances. The environment may affect nutrient loss. Exercising in hot weather can increase electrolyte and mineral losses from sweating. Urinary zinc losses are increased by running and iron losses are increased during ultra marathons through occult blood loss. The temporary immune suppression from these events and training can increase the incidence of upper respiratory infections. In one report ultra marathon runners supplemented with vitamin C at 600 mg per day for 21 days had a significantly lower incidence of upper respiratory infections compared to a nonsupplemented group. Vitamin E also may modulate the acute phase response to exercise and promote a more rapid recovery. Zinc supplementation at 50 mg per day has been shown to block exercise- induced production of superoxide anions in men who ran on a treadmill to exhaustion. The authors feel that until more research is done on ultra endurance athletes, recommendations regarding vitamin and mineral requirements cannot be made. Prior to competition, glycogen storage can be maximized by consuming 8 to 10 gm of carbohydrate per kg of body weight each day (or 70% of the calories from carbohydrates per kg body weight each day) for 2 or 3 days before the event. Four hours before the event ingestion of 4.5 gm of carbohydrate per kg may enhance performance by maintaining blood glucose levels. To recover athletes should consume 1.5 gm of carbohydrate per kg body weight immediately after the exercise and every 2 hours following the exercise for at least 6 hours to replenish the muscle glycogen stores. Foods with a high glycemic index are more effective in glycogen repletion than low glycemic index foods. During prolonged competition or training an athlete should ingest 250 to 300 ml of a carbohydrate solution at 6 to 8% which contains electrolytes every 30 minutes throughout the exercise period. When exercising in hot weather at an intensity of greater than 70% of maximal capacity, additional fluid, which should not exceed 1600 ml per hour, should be consumed to reduce the risk of dehydration. For rehydration an athlete should ingest, over a period of several hours, at least 1 liter of fluid for every kg of body weight lost. Fluid and sodium replacement are enhanced when the rehydration beverage contains 40 mmol of sodium per liter. 21488 [exe, nut] Studies of nineteen western European and five non-European countries showed premature mortality from coronary heart disease in men below the age of 65, related to food, antioxidant vitamins and other nutrient supply data, between 1985 and 1987. The phenolic antioxidant-rich foods such as wine, vegetables, and vegetable oils were inversely related to coronary heart disease. The alpha- tocopherol component of vitamin E was strongly related to coronary heart disease across Europe. The major determinant of alpha- tocopherol supply was usually sunflower seed oil. Vitamin C and beta-carotene gave moderate correlations. For the majority of countries, there was an inverse association between the supply of vitamin E and coronary heart disease. The authors conclude that vitamin E may provide just as good an explanation as wine for the paradoxically low rates of coronary heart disease in several European countries which have relatively high saturated fat intakes. 21732 [car] The current recommended dietary allowances for calcium and phosphate in 2 to 6-year-old children are both 800 mg per day. There is little data to support these recommendations according to Dr. Jan, Professor of Pediatrics, of the Utah School of Medicine in Salt Lake City. He and his associates recently found that children who ingest more than 11,000 mg per day of each mineral have higher bone mineral content. This study evaluated 50 children between 2 and 6 years of age doing 3 day dietary records, and bone mineral content using single photon absorptiometry. The average daily intake of calcium was 1,087 mg and their average intake of phosphate was 1,202 mg. Dietary intake of both minerals correlated with bone mineral density. Children who ingested less than 1,100 mg of calcium and phosphate per day had a lower bone mineral disease score than those who ingested more. 22303 [end, nut, ost, ped] This study evaluated 2,906 healthy, nonsmoking males on health habits and physical activities and a symptom-limited exercise test. There was a gradual increase in high density lipoprotein cholesterol observed with increased miles run. Most of the changes were associated with distances of 7 to 14 miles per week. Levels of low density lipoprotein cholesterol, triglycerides and the ratio of total cholesterol to HDL lipoprotein cholesterol also improved with weekly mileage. The HDL lipoprotein cholesterol levels correlated significantly with all exercise components, anthropometric measurements and alcohol consumption. These results suggest a dose-response relationship between miles run per week, high density lipoprotein cholesterol and other lipoprotein-lipid levels. Most of the changes occurred in those who ran between 7 and 14 miles a week at a mild to moderate intensity. It is also noted there is a higher risk of injury (foot, ankle, knee, hip) with higher mileage. It appears unnecessary and perhaps counterproductive for most people to jog beyond 14 miles per week to increase HDL-C levels. 21885 [car, exe] The total number of P450 genes is estimated to be at least 60 and possibly several hundred. The cytochrome P450 (CYP) superfamily nomenclature is based on a divergent evolution of genes. Most of the enzymes within gene families CYP1, CYP2, CYP3 and CYP4 appear to have evolved as the body's primary defense against the onslaught of chemicals confronted on a daily basis. More than 3.5 billion years ago, cytochrome P450 enzymes were designed as necessary components of single, transduction pathways. In the past billion years most P450 enzymes have become responsible for detoxification of numerous foreign chemicals. During such oxidative metabolism it is increasingly apparent that these enzymes generate toxic intermediates. More than a dozen human P450 polymorphisms have been characterized. Genetic variability in P450 expression is therefore likely to have significant bearing on individual susceptibility to chemical toxicity. Genetic differences in human P450 expression are outlined and their relationship to autoimmune disease is examined. The speculative role of P450 polymorphism in several lupus-like disorders is reviewed. Cytochromes P450 enzymes are thought to be the primary interface between humans and chemical exposure. The identification of pharmacogenetic polymorphisms, both P450 and other drug-metabolizing enzymes, represents a major current focus of research, aimed at understanding individual variability in chemical toxic responses. Molecular advances, such as the recent availability of many polymerase chain reaction genotyping assays, now enable researchers to identify individual genotypes quickly and correlate them with particular toxic responses. Such studies have given insight into the role of P450 and other foreign chemical-metabolizing enzyme polymorphisms in many human diseases, including certain toxicities and cancer. Conditions include idiopathic, chronic, active hepatitis, drug- induced hepatitis, anticonvulsive hypersensitivity, autoimmune polyendocrine syndrome Type I and idiopathic Addison's disease. 21913 [aut, met] Studies over the last 25 years strongly support the view that raised extracellular magnesium is protective in myocardial ischemia and reperfusion. In the 1970s it was shown that the recovery of the dog heart function after global ischemia with hypothermia induced by aortic route infusion was greatly improved when the basic Ringer's solution was supplemented with 30mM of magnesium. Studies indicated that high extracellular magnesium added to the protection to potassium based cardioplegia by interacting with calcium, sodium and potassium ions and by preventing tissue magnesium loss during ischemia. This lead to the formulation of the St. Thomas' Hospital cardioplegic solution. It was also found, later in animal studies, that high magnesium did not require simultaneous high potassium in order to improve post ischemic function. In a study of reperfusion injury after severe global ischemia in rabbit hearts, it was found that high magnesium improved the final recovery of cardiac function, and by combining high magnesium with low calcium lead to a further improvement. The main effect of high magnesium alone were to reduce tissue magnesium loss and mitochondrial calcium accumulation but not to prevent cellular calcium overload. Small clinical studies since the 1980s indicate a marked reduction in mortality rates by magnesium during acute myocardial infarction. In the first large study the Leicaster Intravenous Magnesium Intervention Trial II (LIMIT-2) in 2,316 patients with suspected acute myocardial infarction. Over a 5 year period myocardial infarction was confirmed in 65%. There was a control group and a magnesium group. Both groups received the same basic treatment which include thrombolysis (35%) and aspirin (65%). The magnesium infusion was a 5 minute bolus of 8mM followed by 65 mM over 24 hours resulting in a mean maintained serum magnesium of no more than 1.5 mM. There was a reduction in 28 day all cause mortality rate by 24%; a parallel 25% reduction in the incidence of acute heart failure within the coronary care unit and long term reduction in cardiac mortality by 21% and all cause deaths by 16%. There was no antiarrhythmic effect found. The benefits appear to be due to the myocardial salvage by magnesium infusion during the acute phase. To explain the benefit of a moderate elevation of serum magnesium in this LIMIT-2 study one has to consider magnesium both as a nutrient which treats a relative deficiency and as a drug. Magnesium results in a reversal of coronary vasospasm; enhancement of endothelial prostacyclin production; and inhibition of platelet aggregation; and improved hemodynamics obtained through a reduction in after load in a moderate lowering of the heart rate. Thus magnesium is an important protective agent in acute myocardial infarction which may work in at least 3 major ways: In delaying ischemic injury; in reversing coronary flow restriction; and in aiding recovery of cardiac metabolism. The end result will be improved post ischemic recovery of cardiac function. 22164 [car] This study evaluated 832 men between 45 and 65 years of age who were free from cardiovascular disease at baseline. There were 97 incident strokes upon follow-up. There was an age adjusted risk of stroke that decreased across increasing quintiles of servings per day of fruits and vegetables. The relative risk for all stroke was .78 for each increase of 3 servings per day. For complete stroke the relative risk was .74; for completed stroke of ischemic origin the relative risk was .76; and for a completed stroke of hemorrhagic origin the relative risk was .49. The authors conclude that intake of fruit and vegetables may be protective against stroke in men. The protective effect does not appear to be mediated through effects on blood pressure. Increasing the intake of fruits and vegetables may not only have a beneficial effect on the incidence of stroke, but other chronic diseases that are leading causes of morbidity and mortality in western societies. 22155 [car] The director of the Bogalusa Heart Study is recommending universal cholesterol screening of children beginning at the age of 4 based on new findings. Selective screening results in underdetection of high cholesterol children. In evaluating over 8,000 children and their parents in the town of Bogalusa, it was found that parental evidence of cardiovascular disease rises as both children and their parents age (Circulation, 1995;91:365- 371). Offspring of parents who have a heart-attack history were significantly overweight after 10 years of age and showed elevated levels of total cholesterol, VLDL cholesterol, LDL cholesterol, insulin and glucose after 17 years of age regardless of their weight. Some of the researchers encourage looking not only for a family history of heart disease in the parents and grandparents, but also for all heart disease, especially premature heart disease or high cholesterol before the age of 55. The professor and chair in the Department of Epidemiology and Biostatistics at the University of California, San Francisco, Dr. Stephen B. Hulley, feels that cholesterol screening in children may do more harm than good. Psychologically having this "air" of adult disease and death hanging over them would be intense. They would be asked to eat differently from their peers at an age in which growing up is difficult enough. At best, universal childhood screening could be used as a "gentle one-time review" of risk factors and beneficial lifestyle. 21703 [car] This study evaluated over 8,000 vaginal deliveries in 3 different cohorts using normal vaginal delivery without episiotomy, normal noninstrumental vaginal delivery with episiotomy, and instrumental vaginal delivery with episiotomy. Over a 7 year period between 1984 and 1991 it was found that among those undergoing noninstrumental delivery, no reduction in the incidence of major lacerations could be shown following episiotomy. In those undergoing episiotomy, the incidence of major lacerations was significantly higher following instrumental delivery. 21992 [obs] This is a case report of a 34-year-old woman who had worsening asthma. She had had asthma since 14 years of age. She married a baker and soon after experienced asthma when working in the bakery. An allergist diagnosed her allergy to wheat flour, so she stopped working in the bakery. The family moved to a house that was located far away from the bakery. Her asthma worsened and, in addition, she had year round rhinitis. Skin prick testing was strongly positive to uncooked aspergillus orizae à- amylase. She also developed a systemic reaction with nasal itching, runny nose and wheezing. She was given a double-blind, placebo-controlled food challenge with à-amylase resulting in coughing, wheezing and a decrease in peak expiratory flow rate. The patient was told to avoid all bakery products containing à- amylase. She followed this advice and her improvement was complete. She had no asthma attacks during the 4 subsequent months. 22047 [all] A rat model evaluated experimental allergic encephalomyelitis with the treatment of hyperbaric oxygen. Animals were exposed to two 3 hour 2 ATA treatments within 24 hours. There were 3 HBO protocols used: a 10 day preventive treatment, a 3 day preventive treatment and a 10 day symptomatic treatment. This study showed that HBO treatment does not reduce the blood brain barrier disturbance and cerebral edema in experimental allergic encephalomyelitis. It tends to provoke reversible blood brain barrier breakdown. Preventive HBO treatments result in modification of the course of experimental allergic encephalomyelitis possible by immune suppressive effect during the initial sensitization step. The HBO treatment generates oxygen free radicals. The variation in the intensity of the blood barrier injury might be due to differences in the animal's susceptibility to oxygen. 22712 [all, neu] This is a case report of a 53-year-old female who came in because of strange feelings in her feet and legs during the previous 3 weeks. She also was clumsy in handling eating utensils, and her handwriting had deteriorated. She had an MCV of 103 with a few hypersegmented neutrophils. The patient began to experience chest discomfort when climbing stairs, as well as a sore mouth and tongue. She saw a dentist who referred her back to her physician for evaluation of B12 deficiency. Her hematocrit was now 24% down from 35% and the MCV was 117 um3. The patient received B12 injections. The patient's symptoms completely resolved during the next 6 months. When peripheral neuropathy is involved and cobalamin deficiency is the cause, most patients should receive 1,000 mcg of B12 per injection. The author feels it is a mistake to administer only 100 mcg per injection. A reasonable schedule for initial replacement is 3 or 4 alternate-day injections followed by an injection 2 weeks later and one 4 weeks later. A 1,000 mcg maintenance injection should be given monthly. Most patients note neurologic improvement several weeks after treatment has begun. If they are really anemic they will notice improvement within the first week. Patients who have residual symptoms after 6 months should not give up since maximal benefit may not be achieved until 18 months thereafter a little improvement will occur. The next case is a 72-year-old woman who presented with a 2 week history of progressive paresthesias in the feet. Two weeks before the onset of symptoms she had undergone a lengthy plastic surgery under nitric oxide anesthesia. Her hematocrit was 34% and her MCV was 112 um3 and a serum B12 level less than 100 pg/ml. Serum gastrin was grossly elevated but her B12 absorption was normal. The patient was advised to take a daily vitamin pill that contained 10 ug of vitamin B12. Her paresthesias gradually resolved. Six months after she began taking the multi-vitamins, her serum B12 level was 308 pg/ml. It was noted that nitric oxide destroys vitamin B12 and is a concerning anesthetic in patients with marginal cobalamin stores or early deficiency. The next case report is an 80-year-old male with generalized fatigue and aching in the lower legs. He was found to have a hematocrit of 41 and an MCV of 85. Serum homocysteine and methylmalonic acid levels were above normal. The serum B12 level was subnormal at 180. The patient received intramuscular vitamin B12 injections and after 6 months serum homocysteine and methylmalonic acid had fell into the normal range and serum B12 levels had risen to 400 pg/ml. His symptoms did not improve. 22845 [hem, neu, nut] Twenty-eight patients with allergic asthma, most with a sensitivity to house-dust mites, randomly received either an oral homeopathic immunotherapy to their principal allergen or a placebo. This treatment was given in conjunction with their unchanged conventional care. A difference in visual analog score in favor of the homeopathic immunotherapy occurred within 1 week of starting the treatment and persisted up to 8 weeks. A meta-analysis of all 3 trials provided evidence that homeopathy does more than placebo. For today's science the main barrier to the acceptance of homeopathy is the issue of serially vibrated dilutions that lack molecules of the original substance. The ability of water or alcohol of fixed biochemical composition to encode differing biological data is questioned. Said another way, does the þchaos- inducing vibration, central to the production of homeopathic dilution, encourage biophysically different fractal-like patterns of diluent, critically dependent upon the starting composition?þ. Theoretical physicists seem to be able to accept this more easily than pharmacologists. Nuclear magnetic resonance alterations in homeopathic dilutions have been reported. If these are reproduced this may offer promise to understanding homeopathic remedies. At present the critical tests are clinical evaluations. The authors conclude, þOur results lead us to conclude that homeopathy differs from placebo in an inexplicable but reproducible way.þ 21470 [all, hom, med] This study evaluated serum levels of manganese and 24-hour manganese excretion by urine in 29 patients with Parkinson's disease and 27 matched controls. There was no difference found between the 2 groups and the authors conclude that serum levels and urinary excretion of manganese are unrelated to the risk of developing Parkinson's disease. 22804 [neu] This study evaluated B12 status in 85 consecutive patients with severe sickle cell disease compared to 100 healthy controls between 17 and 60 years of age. 43.5% of the 85 patients had vitamin B12 levels below normal values without macrocytosis or hypersegmentation. The mean level of vitamin B12 in the remaining 48 patients was normal at 233.3 pmol/l which is below the mean of the normal controls at 327.7 pmol/l. Patients with low vitamin B12 levels had significant improvement when treated with vitamin B12 1 mg intramuscularly weekly for 12 weeks when compared with normal B12 levels. The authors conclude that many patients with severe sickle cell disease may suffer from unrecognized vitamin B12 deficiency. The authors note that although vitamin B12 deficiency is rare in normal individuals it is not uncommon in conditions associated with increased demand or an inadequate supply of absorption. These conditions include concomitant microcytosis from iron deficiency anemia, thalassemia, traits, inherited HbE and HbD hemoglobinopathies and chronic lead poisoning. Functional B12 deficiency can occur in those with normal or elevated vitamin B12 levels, in myeloproliferative disorders, leukocytosis or exposure to nitrous oxide. In sickle cell patients, vitamin B12 deficiency may be looked for in those with vague neurologic or psychiatric symptoms. Routine B12 measurements should occur for these suspected cases. Minimal folate supplement, only 1 mg per day for patients with sickle cell and other hemolytic anemias should be given. Performing ancillary tests when necessary such as the finding of decreased leukocyte alkaline phosphate, increased urinary methylmalonic acid, increased serum methylmalonic acid and homocysteine in patients with suspected B12 deficiency and normal B12 levels, gastroscopy and measurement of gastric pH to rule out achlorhydria and vitamin B12 supplement in cases where proper tests are not available. 22731 [hem] This article reviews the role of role of protein, vitamin A, zinc, vitamin C and E, iron in wound healing. Evidence of significant malnutrition has been found in alcoholics, the poor, the elderly and the chronically ill. Protein malnutrition has been found in up to 25% of all hospitalized patients while 50% of general surgery patients experience moderate to severe protein malnutrition. Inadequate nutrition slows wound healing, decreases immunocompetence, increases susceptibility to infection, causes longer hospital stays and increases mortality and morbidity. Addressing nutritional problems will not only help the patient but reduce health care costs. To support wound healing, the USRDA goes up to 2 to 4 gm per kg per day as opposed to .8 gm per kg per day in healthy subjects. Protein deficiency is considered mild when serum albumin measures 3.5-3.9 g/dL, moderate at 2.5-3.5 g/dL, and severe at less than 2.5 g/dL. Vitamin A deficiency usually occurs without symptoms and is difficult to detect outside a hospital setting. Vitamin A deficiency is common when measured in hospitalized patients. Individuals who are severely injured or burned can become vitamin A deficient, which impedes wound healing. Vitamin A plays an important role in each stage of wound healing. Vitamin A enhances the early inflammatory phase. In vitamin A deficiency there is a reduction in fibronectin on the wound surface with a subsequent decrease in cell chemotaxis, adhesion, and tissue repair. Postoperative vitamin A supplementations for 7 days can increase collagen synthesis, the bursting strength of the scar, and lymphocyte activation. A large supplemental dose of vitamin A can reverse the postoperative suppression of immune response and improve healing retarded by stress, diabetes, and radiation. Infrequent high doses of vitamin A are generally safe when given for vitamin A deficiency. Vitamin A can exhibit an anti-steroid activity. Wounds retarded by anti-inflammatory steroids are stimulated by retinoids far more than normal wounds. To avoid anti- steroid activity, vitamin A can be applied topically to the wound or with sponge implants. Topical vitamin A increases the epithelialization of wounds and improves the cosmetic appearance of scars. Dietary sources include liver, dairy products, egg yolk, yellow and dark green leafy vegetables and deep yellow or orange fruit. Zinc is one of the oldest agents that can help promote wound healing. Zinc was used topically as calamine lotion as far back as 1500 B.C. by the Egyptians. There are approximately 200 zinc requiring enzymes in the body. DNA polymerase is a zinc dependent enzyme which is needed for cell proliferation during healing. Superoxide dismutase is required to remove superoxide radicals produced by leukocytes during debridement. Marginal zinc deficiency is quite common in the United States. The poor, inner city dwellers, and pregnant or breast feeding women are also at risk of zinc deficiency. Plasma zinc concentrations of less than 70 g/dl is considered deficient. The soil is poor in zinc in 32 states. Vegetarians are at risk for zinc deficiency since cereal grains are low in zinc and more is removed during the milling the milling process. In zinc deficiency there is delayed closure of wounds and ulcers. The collagen produced has reduced tensile strength. Zinc deficiency also affects the immune system by causing a reduction in lymphocytes, natural killer cells, and the size of the thymus. There is an increased susceptibility to recurring infection and poor wound healing. Topical zinc oxide inhibits bacterial growth for extended periods, especially of gram-positive bacteria. Hence, zinc oxide is incorporated into dental cement for periodontal dressings. Smell, taste and vision may also be affected by zinc deficiency. Only those with low plasma zinc levels respond positively to oral zinc administration. Postsurgical patients have a low tolerance for food intake and dietary zinc. Zinc can be given by intravenous drip to improve clinical wound healing. Intravenous nutritional therapy of surgical patients can improve healing if it contains trace elements. The benefit is even better if given before surgery. There is an apparent decrease in serum zinc during wound healing. Topical administration of zinc chloride as a spray or ointment reduces the size of the wound, shortens healing time, and produces less dehiscence. Zinc oxide is effective in enhancing wound healing while zinc sulfate is not. Vitamin C is required for the hydroxylation of proline and, subsequently, for the synthesis of strong collagen. Poor wound healing is one of the symptoms of scurvy. A deficiency of vitamin C can lead to the breakdown of already healed wounds. Plasma vitamin C levels decrease during fracture, burns, or major surgeries. The USRDA of 60 to 100 mg increases 500 to 1500 mg per day in burn victims. Stress associated with injury and wound healing results in an increased need for vitamin C. Wound healing is directly accompanied by the oxidation of ascorbic acid. Levels of vitamin C rise in healing tissue and return to normal after it is healed. Dietary supplements from 100 to 300 mg to 1 gm per day can return plasma levels to normal in postoperative patients. Vitamin C in combination with pantothenic acid has been shown to increase skin strength and fibroblastic content of scar tissue. A deficiency of both causes prolonged wound healing. After treatment for 24 hours with vitamin C, human skin fibroblasts in culture showed a 2 to 3-fold increase in type I collagen synthesis. Megadoses of vitamin C, even when given to patients with normal vitamin C levels, can accelerate collagen formation above the degeneration rate of damaged collagen. Vitamin C is useful in leg ulcers. Vitamin C shortly after thermal injury can significantly reduce tissue necrosis. Vitamin E is a lipid soluble antioxidant which accumulates in the cell membranes where it protects polyunsaturated fatty acids from oxidation by free radicals. The USRDA is 15 IU per day. Vitamin E has an anti- inflammatory action due to its ability to inhibit phospholipase-A2 activity and, therefore, the production of prostaglandins. Vitamin E also has a lysosomal-stabilizing ability, which is probably related to its ability to stabilize membranes in general. Vitamin E can also inhibit collagen synthesis. Tendons allowed to heal in the presence of vitamin E had a significantly lower peak strength after an 8 week period than those healed in the absence of vitamin E. Back incisions showed a significant decrease in tensile strength from retarded collagen synthesis in a group of rats treated for 7 days with vitamin E. It was noted that when the incisions did heal, there was a marked decrease in scar formation and the apparent size of the zone of injury. Topical administration for cosmetic purposes may be beneficial. Some patients have developed rashes from topical vitamin E application. Vitamin E enhances the immune response in a dose-dependent fashion. Vitamin E has normalized the breaking strength of wounds in patients receiving preoperative irradiation, probably because of its antioxidant capabilities. Vitamin E in combination with other drugs is recommended for the treatment of burns. Improved wound healing was also observed in patients with a history of deep vein thrombosis. After 4 weeks of oral vitamin E supplementation stasis ulcers were significantly improved. The enzyme that produces deoxyribonucleotides for DNA synthesis, ribonucleotide reductase, requires iron as a cofactor. Cells cannot divide without prior DNA synthesis, so a lack of iron would impair the proliferation of all cells involved in wound debridement and healing. Serum iron levels less than 30 ug/100 ml are deficient. Normal values are 70 to 130 ug/100 m/L. Iron is also involved in the hydroxylation of proline. Proline hydroxylase requires iron. Without hydroxylation of proline, collagen triple helix formation is unstable and results in collagen weakness. Therefore, wound healing during iron deficiency is weaker. Some critically ill patients may require therapeutic doses of nutrients that are approximately 10 times the recommended daily allowance. 21582 [imm] Fifty-eight early postmenopausal women attending metabolic bone disease outpatient clinics were randomly allocated into 4 treatment groups and monitored for up to 4 years. All of the patients received 1 gm per day of elemental calcium. One group received percutaneous administration of hormone replacement therapy and another group received intermittent cyclical etidronate. Another group received both of those therapies and the last group received calcium alone. The combined therapies resulted in an increase in bone mineral density of the vertebra of 10.9% and in the femora of 7.25% at 4 years. For the patients treated with the intermittent cyclical etidronate, the increase was 6.79% and 1.2%, while hormone replacement therapy was 6.78% and 4.01% increase in bone mineral density in the vertebra and femora, respectively. The group treated with calcium alone lost 3.81% and 4.96% of the bone mineral density in the vertebra and femora. Patients who received no specific treatment lost 8.58% from the vertebra and 7.83% from the femora over 4 years. This study shows those treated in early menopause had an additive effect of intermittent cyclical etidronate and hormone replacement therapy on bone mineral density in both the hip and vertebra. The combined therapy prevented the occurrence of osteomalacia associated with etidronate. 22846 [ort, end] This is a review article on the effectiveness of cholesterol- lowering diets. Two trials of dietary therapy utilizing intensive individualized counseling in persons at usual risk for coronary artery disease achieved 75 to 80% of the cholesterol lowering predicted by metabolic ward studies, and produced 5 to 14% reduction in total cholesterol levels. Four studies in high risk individuals exceeded the predictions and achieved a 4% to 17% reduction in total cholesterol levels. Six of 7 trials of diet therapy for secondary prevention had similar benefit. Four trials utilizing the population approach achieved smaller but often significant reductions in total cholesterol levels of 1 to 11%. The effectiveness of diet is enhanced when individualized counseling is utilized, follow-up is maintained and weight reduction is achieved. It is noted that the efficacy of a cholesterol-lowering diet has been clearly shown in the metabolic diet studies where dietary intake can be maximally controlled and confounding variables can be taken into account. Even though approximately 10% of the population at large and a higher percentage of patients in tertiary lipid clinics are diet resistant, dietary modification can still play an important role in lowering cholesterol levels and reducing the risk to coronary heart disease around the world. 21969 [car] This is a review on how primary care physicians can encourage abstinence as a means to promote healthy living. Educating teens and their parents about the consequences of premarital sexual activity may be an important factor in reducing the risk to many sexually transmitted diseases and AIDS. Discussions regarding the high prevalence and inevitability of teenage sexual activity and the lack of ability of parents and society to alter this trend generally leads to contraceptives and condoms being the answer. The author notes that this tertiary preventive strategy has had limited effectiveness in reducing the consequences of premature sexual intercourse. Primary care physicians promote primary prevention for unhealthy behavior such as smoking, drug addiction, etc. The author feels the this is the time to do the same with premature sexual activity. Effective educational strategies to reduce adolescent sexual activity and its consequences in both teens and their families may be more effective than what is presently occurring. The author reviews factors that protect against early initiation of sexual intercourse and factors that contribute to the early initiation of intercourse. The authors reviews the family, parenteral supervision, the school, religion, personality and demographics in each of these areas. Strategies for promoting abstinence in adolescents is also reviewed as well as a reading list on adolescent sexuality for parents and teens. 22598 [sex] A 15 minute questionnaire was given to the pediatric house staff in an academic training center to evaluate their breast feeding attitudes, knowledge and confidence in managing breast feeding problems. The participation rate was 53% or 29 individuals. Overall there was a supportive attitude towards breast feeding. Women agreed more strongly than men that pediatricians should strongly encourage mothers to breast feed and disagreed more strongly than men that breast feeding is instinctive. Even though supportive of breast feeding the house staff was not knowledgeable about breast feeding management, answering only 53% of the questions correctly. Only 14% of the doctors described themselves as confident or very confident to manage common breast feeding problems. The authors conclude that physicians in training have very limited knowledge of breast feeding management. To be truly supportive of breast feeding the physicians need to receive didactic and clinical instruction on breast feeding management. 21844 [nut, obs, ped] This article reviews the theory that cerebral free radicals are removed during sleep. Sleep functions as an antioxidant for the brain. Sleep is required to insure there is minimal neuronal damage due to free radical accumulation during waking. Most people can tolerate a few days without sleep and fully recover. In animal models, prolonged periods of sleep deprivation caused neuronal damage. The free radical theory of sleep expresses sleep as a consequence of neuronal metabolism. It also develops a concept of sleep as an antioxidant defense in and of itself. 21419 [end, neu] This was a nationwide case-controlled study covering a region with 78% of all births in New Zealand between 1987 and 1990. Interviews were completed with the parents of 393 cases of infants who died with sudden infant death syndrome in the postneonatal age group and 1,592 controls. 26% of the SIDS deaths were explained by bed sharing among infants of smoking mothers and 3% by bed sharing among infants of nonsmoking mothers. The majority of SIDS deaths that are attributed to bed sharing occur among infants of smoking mothers. This data should not be interpreted to suggest that bed sharing where the mother is a nonsmoker is safe or protective against SIDS. The authors conclude that an extra 3% of sudden infant deaths could be saved by a general message for all infants not to bed share compared to messages targeted to the infants of smoking mothers. Current favorable attitudes towards infant bed sharing may jeopardize the acceptance of other cot death prevention messages if it is perceived that the evidence does not justify a general recommendation against this practice. 22675 [ped] Twenty-four hour dietary recall was used in recording dietary intake and meal frequencies during a typical flight day. Of the female pilots 75% experienced air sickness and 24% of the males experienced it. In review, the study notes that increased dietary intakes of high sodium snacks and milk and cheese products are correlated with increased air sickness. Higher density foods increase air sickness. This study supports eating 3 or less meals per day and for males eating foods high in carbohydrate content to help prevent air sickness. Also not eating meats, diary products or foods rich in sodium just prior to flight appears to be beneficial. When counseling a female who is susceptible to air sickness one might advise a light meal eaten at least 3 hours prior to the flight that does not consist of high dairy product, high protein rich foods. Females should also consume foods that are high in fruits and vegetables. 22944 [met] Ten lactating females who received cimetidine in a single oral dose of 100 mg, 600 mg and 1200 mg on 3 different days were studied. The researchers found 6 times as much cimetidine in the breast milk as they would have expected. The average dose the infants received was about 6% of the total dose the mothers received. This 6% figure is within the normal therapeutic range for infants. Other drugs or environmental chemicals that have structures similar to cimetidine may also be easily transferred to breast milk. Most drugs get into breast milk by diffusion. Cimetidine may be carried into breast tissue by carrier proteins which transport many of the constituents that normally get into breast milk, such as glucose and amino acids. 21379 [fam, obs, ped] This study evaluated dental caries among children and the relationship to sugar consumption in the total population of 90 countries. DMFT scores tended to increase with sugar consumption. When the data from 29 industrialized nations is evaluated separately there is no evidence of the sugar-caries relationship. There is a considerable lack of strong evidence that a relationship exists between the amount of sugar consumed and dental caries in western societies. In addition to sugar, other factors such as diet, fluoride exposure, and genetics play a role in explaining the variations in caries prevalence. 21449 [den, nut] This study evaluated an in vitro model of zinc sulphadiazines and its effect as an antimicrobial agent in burns. The data showed that the zinc compounds were consistently more potent and were chosen for further development in clinical uses. A similarity between the zinc sulphadiazine and the silver sulphadiazine may be significant to distinguish that from any other zinc sulphadiazine derivative in bioactivity. Zinc sulphadiazine was consistently shown to be a very potent antimicrobial activity and was superior to the other zinc compounds and to silver sulphadiazine. 22836 [sur, tra] This study evaluated 185 patients with a history of recurrent venous thrombosis in 220 controls for the general population. Homocysteine concentrations were measured before and 6 hours after an oral methionine load of .1 gm of elemental methionine per kg body weight. Hyperhomocysteinemia was defined as homocysteine concentrations above the fasting or the post-methionine value for the 90th percentile of controls. Of 185 patients with recurrent thrombosis 25% had fasting homocysteine concentrations above the 90th percentile or the controls. After adjusting for variables the odds ratio was 2.0. A similar result was found for the post methionine value with an odds adjusted ratio for 2.6. The authors conclude that hyperhomocysteinemia is a common risk factor for recurrent venous thrombosis and can lead to a 2 to 3-fold increased risk. The underlying mechanism by which hyperhomocysteinemia can cause thrombosis is unknown. There is some evidence that homocysteine contributes to endothelial damage in the arterial vessel but it is not clear. Another mechanism may be the in vitro effect of homocysteine on factor V activation and inhibition of thrombomodulin dependent protein C activation. There may be a thrombocyte aggregatory component caused by homocysteine. Elevated homocysteine may result from a hereditary defect in enzymes involved in methionine metabolism or it may be due to a vitamin deficiency. The authors did not find lower levels of folic acid or vitamin B12 in patients more than controls. In fact, higher homocysteine concentrations at a given folic acid concentration were found in patients than in the controls. This may suggest that some form of decreased enzyme activity and not vitamin deficiency leads to thrombosis. Several studies have shown that vitamin supplementation can lower homocysteine levels. Whether vitamin supplementation for those high values of homocysteine will be beneficial with respect to prevention or venous thrombosis has to be further studied. 22141 [car] This study evaluated 38 males, 36 to 79 years of age, with squamous metaplasia, of which 21 patients received oral administration of 10 to 20 mg per day of folic acid and 750 mg per day of vitamin B12 for 1 year. The supplemented group showed a significant decrease in their score of cellular atypia, while the control group did not decrease. Plasma folic acid and B12 levels increased significantly in the supplemented groups, while levels in the control group showed a slight increase. The authors concluded that folic acid and vitamin B12 supplementation can reduce cellular atypia squamous metaplasia in heavy smokers. 21829 [can] This study was a placebo-controlled trial of 17 healthy individuals between 24 and 51 years of age who received 400 mg of magnesium for 10 days by consuming Long Life Mineral Water at 200.5 mg per liter, 1.5 liters per day and Magnosolv at 360 mg every other day. Before and after treatment a 7 minute cycle ergometry test was performed at 70% of the personal maximal work load. In evaluating the data, a significant correlation was found between a stress-induced rise in plasmanorepinephrine and blood gas parameters as pO2, HCO3, pH, base excess a.s.o. Blood gas alterations were significantly less pronounced after 10 days of magnesium treatment which correlated with norepinephrine elevations. The stress increase in white blood cells was significantly diminished after magnesium treatment. Magnesium appears to have a calming effect on stress reactions with respect to blood gas changes and white blood cell changes. 21343 [exe] This is a case report of an 83-year-old female who was admitted for increasing congestive heart failure and worsening renal function. She denied a history of digoxin use and was given a loading dose of 1 mg of digoxin over 14 hours on the day after admission and an additional 125 mcg on day two. Six hours later she developed multiple ventricular arrhythmias including ventricular tachycardia. She then divulged a prior history of digoxin treatment. Her serum digoxin level was greater than 6.2 nmol/L 8 hours after her last dose. Her admission digoxin level was found to be at the very upper border of normal. She was admitted to the coronary care unit and given an IV bolus of 2.47 gm (10 mmol) of magnesium sulfate, injected over 5 minutes. Five minutes later her ventricular tachycardia stopped and she developed a junctional rhythm with a ventricular rate of approximately 90 bpm. Within a few minutes a stable rhythm emerged. After approximately 15 minutes she developed intermittent bursts of non-sustained monomorphic ventricular tachycardia lasting up to 30 seconds without any clinical deterioration. Another 2.47 gm of magnesium sulfate was given over 5 minutes followed by a return of the junctional bigeminy. She developed, over the next several days, episodes of nonsustained ventricular tachycardia. On day 9 her serum digoxin level was at 3.0 nmol/L and she was discharged on day 10. Sixteen days after her admission her digoxin was 1.8 nmol/L. Digoxin binds to and inhibits the sarcolemma sodium/potassium ATPase pump leading to increased intracellular calcium concentrations, which enhances myocardial contractility. Magnesium enhances the action of the sodium/potassium ATPase pump without affecting the binding of digoxin. Intravenous magnesium has been shown to stop the digoxin-toxic cardiac arrhythmias in patients without overt heart disease. Hypermagnesemia is unlikely to occur with an initial bolus of 10 to 20 mmol of magnesium, but possibly could occur with continuous infusions or with repeat doses in patients with digitalis toxicity. Intravenous calcium is the antidote and should be kept available. 21745 [car] This article notes that more than 90% of pregnant women in the United States use 1 or more nutritional supplements. There is still a great deal of controversy about which if any nutrients should be supplemented, at what quantities and at what stage of pregnancy. This review, in part, is based on the report by the Subcommittee on Nutritional Supplements of the Committee on Nutrition in Pregnancy and Lactation of the Institute of Medicine. The Institute of Medicine Subcommittee recommended that all pregnant women be supplemented routinely with iron. There is still a great deal that is not understood about the prevalence of iron deficiency in pregnancy, consequences of deficiency and the benefits of supplementation. On the average the pregnant woman consumes only about half of the recommended intake of iron. Iron deficiency is assumed to be relatively common in women in the United States as well as other countries. The prevalence of anemia and particularly iron deficiency anemia diagnoses a low ferritin in addition to a low hemoglobin or hematocrit in pregnancy is uncertain. More information is needed to evaluate the general prevalence of iron deficiency anemia in pregnancy. It is difficult to understand why many anemic pregnant women are not iron deficient and what this means in terms of iron supplementation. It is noted that even in nonpregnant individuals serum ferritin concentration can vary up to 25% from day to day. Hemoglobin concentrations as well can vary during pregnancy. Serum transferrin receptor concentration appears to be a promising test that is more useful in the diagnosis of iron deficiency in pregnancy. These receptors are found in cells that have a high iron requirement such as the erythroid marrow and placenta. In a recent study of these receptors in pregnancy almost half of the women evaluated had serum ferritin levels of less than 12 ug/l in the third trimester. Only 17 of the 78 women with low ferritin also had a high transferrin receptor concentration. Conversely, all the women with high transferrin receptor concentrations had low ferritin suggesting this test is quite specific for iron deficiency. Therefore, low ferritin concentrations failed to identify iron deficiency correctly in the majority of women. There is some evidence that iron deficiency results in adverse outcomes during pregnancy such as a high risk of preterm delivery. In general there is very little evidence that iron intervention trials have been effective in reducing the prevalence of iron deficiency and anemia during pregnancy. One explanation for the ineffectiveness of iron supplementation may be poor compliance. Also iron may not be well absorbed from multi- vitamin supplements. Reducing the amount of calcium carbonate in an iron-containing multivitamin and mineral supplement from 350 to 250 mg or reducing the amount of magnesium oxide from 100 to 25 mg results in a doubling of iron absorption. If the multivitamin and mineral is your source of iron then one should obtain one that contains no more than 250 mg of calcium or select a product that contains 60 mg of iron. More research is needed in the frequency of supplementation. There is a substantial amount of data to show that approximately 6 mg of additional iron must be absorbed daily during pregnancy. This amount can be absorbed from a supplement that provides approximately 30 mg of iron per day or 150 mg of ferrous sulfate, 90 mg of ferrous fumarate or 250 mg of ferrous gluconate. Iron absorption becomes less efficient at higher dosages. Approximately 60 mg is absorbed for every 30 mg of supplement. But less than 10 mg for every 120 mg of supplement. It is therefore not very useful to prescribe it in higher amounts. Side effects occur much less frequently in doses less than 30 mg per day of iron. Iron supplements are known to have adverse effects on zinc absorption especially when the ratio of iron to zinc is greater than 2:1. As a precaution the institute of medicine recommends a multivitamin and mineral containing 50 mg of zinc and 2 mg of copper to be taken at a different time of the day when therapeutic doses of iron at 60 to 120 mg per day are prescribed for anemia. Only hemoglobin assessment is recommended routinely to evaluate iron status. A supplement containing no more than 30 mg of iron per day should be provided routinely for nonanemic women to minimize side effects and to minimize the potentially adverse effects of iron on zinc absorption while supplying the theoretic additional iron requirement. When possible, women should avoid taking the iron supplements with milk, coffee, tea or meals because calcium tannins and other constituents of coffee and phytate and food have a strong inhibitory effect on iron absorption. Taking the supplement with orange juice does not help the absorption of iron ferrous cells. Women diagnosed as anemic early in pregnancy should be treated with 60 to 120 mg of iron daily plus a multivitamin and mineral supplement containing zinc and copper. When the anemia is resolved the dose should be lowered to 30 mg per day. The authors note that there is presently little evidence that folate deficiency anemia is a problem in the United States. And since most females enter care after the 6 week period of conception routine folate supplementation may not be of benefit. It is also recognized that the majority of pregnant women are taking folic acid containing multivitamin and mineral supplements. For women who smoke, abuse alcohol, who are carrying more than 1 fetus or for whatever reason do not consume folate dense foods, the Institute of Medicine Subcommittee recommends a supplement of 300 mcg of folic acid per day during pregnancy. Good food folate sources are fruit, juices, whole grains or fortified cereals and green vegetables. In general, the majority of physicians have an attitude that multi- vitamin and mineral supplements may help and will not harm pregnant females. They advise women to take a supplement and in most cases they assume this will minimize the nutritional risk associated with poor eating habits. There still is a general lack of evidence for the routine supplementation of multivitamins and minerals except for possibly iron. Some at risk pregnancy groups include lactose intolerant individuals who consume low amounts of milk and therefore calcium and vitamin D; substance abusers including smokers; adolescents who may require more vitamin B6, folate and calcium; complete vegetarians who need supplements that provide vitamins D and B12; and women who are carrying more than 1 fetus probably need more of all nutrients, especially B6, folate and vitamin C. About 28% of women drink alcohol to moderate or heavy amounts and this is of concern. Other women have chronic conditions such as diabetes or malabsorption syndromes that effect their nutritional status. There is inadequate information with which to judge whether multiple supplements are beneficial. The Institute of Medicine has developed a guide that includes examples of the kinds of questions that should be asked of patients regarding diet and food behavior as well as information on how to collect, evaluate and follow-up on the information that is obtained from a simple food frequency questionnaire. 22195 [gyn, obs] Seven patients with bullous pemphigoid were given a regimen of 2 gm of Tetracycline combined with 2 gm of nicotinamide daily. There was total remission achieved within 6 to 8 weeks after which the dose was gradually tapered. The duration of therapy was approximately 7 months. The mode of action is unknown. Suppression of chemotaxis of neutrophils and eosinophils is thought to be important. Systemic steroids do not appear to clear the bullous eruptions more rapidly than this combination therapy or prevent relapses. This therapy should be considered as the treatment of choice for bullous pemphigus. 22867 [der] This study evaluated 31 patients between 18 and 44 years of age, all suffering from chronic asthma controlled by bronchodilators and/or inhaled steroids. The patients received either active chiropractic spinal manipulation or sham chiropractic manipulation treatment twice weekly for 4 weeks, and then crossed over to the alternative treatment for another 4 weeks. A two week period without chiropractic treatment preceded and followed each phase. No clinically or statistically significant differences were found in evaluating pulmonary function between the active and sham chiropractic interventions. Objective lung function did not change, but over the course of the study nonspecific bronchohyperreactivity improved by 36% and the patient-rated asthma decreased by 34% compared to baseline values. This study does not support the benefit of chiropractic manipulative therapy over sham spinal manipulation in pharmacologically controlled chronic asthma when given twice weekly for 4 weeks. 21713 [all, chi, psy, pul] In a rabbit model, the induction of myocardial ischemia followed by reperfusion was evaluated in a randomized and blinded fashion. An IV injection of normal saline balanced to the pH 7.4, vitamin C at 150 mg per kg or vitamin C plus Trolox at 150 mg per kg plus 100 mg per kg were given prior to coronary occlusion. Infarct size did not differ among the controls, or the vitamin C plus Trolox group. In this model of ischemia and reperfusion antioxidant vitamins did not alter the myocardial infarction size. 22394 [car] This study evaluated 124 patients undergoing a resection of hepatocellular carcinoma. Sixty-four were randomly assigned to receive perioperative intravenous nutritional support in addition to their diet and 60 patients were randomly assigned to a control group. The perioperative nutritional support solution was enriched with 35% branched-chain amino acids, dextrose and lipid emulsion, of which 50% was medium-chain triglycerides, given intravenously for 14 days perioperatively. There was a reduction in the overall postoperative morbidity rate in the group that received the nutritional support compared to the control group (34% versus 55%). This occurred mainly because of fewer septic complications. There was a reduction in the requirement for diuretic agents to control ascites, less weight loss after hepatectomy, and less deterioration of liver function as measured by the change in the rate of clearance of indocyanine green. Most of these benefits were seen in patients with underlying cirrhosis who underwent major hepatectomy. There were 5 deaths during hospitalization in the perioperative nutrition group compared to 9 in the control group. The authors conclude that perioperative nutritional support can reduce complications after major hepatectomy for hepatocellular carcinoma associated with cirrhosis. 21421 [hep, nut, sur] This article reviews elevations of blood manganese concentrations in 3 patients with biopsy-proven hepatic cirrhosis who had neurologic dysfunction. Magnetic resonance imaging noted accumulation of manganese in the brain which probably contributed to the neurologic dysfunction in patients with liver disease. These patients were between 49 and 65 years of age. It is noted that manganese toxicity and chronic liver disease are associated with very similar clinical, imaging and pathological abnormalities. Manganese toxicity is usually associated with increased intake from occupational exposure poisoning. The authors believe that manganese intoxication can also be caused by impaired elimination of normal dietary manganese. Impaired liver function can lead to manganese overload despite a normal intake. If manganese can be associated with neurologic dysfunction then therapies that diminish manganese intake or enhance its elimination may be beneficial. 21512 [gas, hep, tox] This study evaluated the hypothesis that 3 weeks of oral lactate supplementation affects post exercise lactate disappearance in untrained athletes. Eight men received lactate supplementation which was a drink containing 10 gm of lactate which was of the following composition: 8.2 gm calcium lactate powder, 6.25 ml sodium lactate solution (60% lactate), 2.05 ml of potassium lactate solution (60% lactate), diluted to 100 ml with water. The mineral quantity ingested as a result of the lactate salts amounted to 1.5 gm calcium, 1 gm sodium and .5 gm potassium. The drink was given twice a day or a placebo was given in 7 patients which contained maltodextrin. The 3 week supplementation of oral lactate did not result in differences in lactate disappearance. This data does not support the hypothesis that regular oral lactate intake at rest enhances the removal of lactate during and following exercise. 22968 [exe] Thirty-nine patients were evaluated by endoscopy. Then, after an overnight fast, blood was drawn and plasma was assessed for ascorbic acid analysis. A nasogastric tube was inserted and a baseline gastric juice sample was obtained; then, 500 mg of vitamin C was injected intravenously. Gastric juice samples were taken in the patients at 30 and 60 minutes after the injection. In this study there were 11 black males, 4 white males, 17 black females and 7 white females. Twenty-four of the patients were infected with helicobacter pylori. Compared to those who were not infected, those who were infected had a smaller increase in ascorbic acid in gastric juice after intravenous injection. These differences were not statistically significant. Whites had significantly greater increases in vitamin C in gastric juice than blacks both at 30 minutes and at 60 minutes. The black- white disparity in vitamin C was independent of helicobacter pylori status and pH. Whites were more likely than blacks to have a large increase in gastric ascorbic acid at 30 minutes and 60 minutes after the injection. When compared with patients with a gastric acid pH of less than 2, patients with a gastric acid pH of 2 or more were less likely to have a large increase of vitamin C at 30 and at 60 minutes. After controlling for variables there was no significant association between helicobacter pylori status and the observed change in vitamin C concentrations in the juice. The differences seen in the transport of vitamin C in the stomach between ethnic groups and at different levels of pH are large and highly statistically significant, despite the small sample size. The helicobacter pylori effect appears to be mediated by its capacity to increase gastric pH, a finding which can be explained by the oxidation of vitamin C in the gastric lumen. Racial and ethnic characteristics appear to play a role in the gastric acid secretion of vitamin C that is independent of helicobacter pylori status and pH, and is therefore probably independent of the changes in the gastric microenvironment brought on by the infection. These findings suggest that both oxidation of vitamin C in the gastric cavity and efficiency of its transport from the blood to the gastric lumen are important. 21902 [can, gas] This is a thoughtful review on the role of the scientific community in treating animals that are used for research. The author notes that the social concern about animals with regards to research is from the fact that many people believe that animals deserve a moral status considerably higher than they have traditionally received. Researchers should not expect that this concern for the welfare of laboratory animals is a transient fad. It is more likely to grow as a social movement recognized and a notice that moral questions have done. Mechanisms need to be set in a place which excludes invasive research which produces no benefit but simply advances trivial knowledge or careers. Researchers who throughout their careers have taken this particular use of invasive animal research for granted are not the best sources to eliminate this use. Another concern of the animal research community ought to be to deal with the anticipatory manner in the way in which animals are maintained. Laboratory animals have traditionally been kept in husbandry conditions which are convenient to researchers in terms of cleaning and maintenance. The standard stainless steel or polycarbonate rodent cage was developed for human convenience and efficiency and not for the regard of the animal's welfare. Some have suggested that being forced to live under these conditions is a greater source of suffering than the actual experimental manipulations. An ideal design for these husbandry systems ought to be for the satisfaction of the complex set of mental and physical interests which make up the animal's nature or telos. 22337 [eth] This is an extensive review article on the role of dietary protein and blood pressure. Animal models have suggested that the level of protein in the diet can have a subtle but significant effect on the way an animal responds to the damaging effects of sustained high blood pressure. The increased consumption of protein and metabolism may enhance the excretion of sodium which may be one of the causative factors in the development of cerebral lesions as a result of high blood pressure. There is increasing data that suggests a strong relationship between adequate dietary protein intake with reduced sodium intake would reduce the severity of hypertension. As a whole the data suggests that adequate or increased amounts of dietary protein may be beneficial for hypertension or cerebrovascular disease while a low protein diet may be more appropriate for renal vascular disease. 22499 [car, nep, neu] Vitamin K is important to proteins that are in bone. Serum vitamin K levels are reported to be reduced in older individuals and persons with osteoporotic fracture. Circulating levels of undercarboxylated osteocalcin may be a sensitive marker of vitamin K inadequacy and have been reported to be increased in both postmenopausal women and individuals who sustained hip fractures. It is possible that vitamin K indirectly affects the skeleton by control of renal calcium excretion. The effect of vitamin K antagonists on both renal calcium excretion and bone density is controversial. Thus, many of the reports on vitamin K insufficiency and its role in osteoporosis are conflicting. Vitamin K comes from the diet as phylloquinone or vitamin K1 which is from plants. Menaquinones, referred to as vitamin K2, is produced by bacteria in the bowel and supplies an unknown fraction of the daily requirement. Unlike other fat soluble vitamins, bodily vitamin K stores are rapidly depleted and a rapid onset of deficiency is possible. The metabolic role of vitamin K is required as a cofactor for vitamin K-dependent carboxylase, the microsomal enzyme responsible for post- translational conversion of specific glutamyl to the gamma- carboxyglutamyl residues in a limited number of proteins. The ability of gamma-carboxyglutamyl residues to bind to CA2+ ions and promote protein-CA2+-phospholipid interactions has been shown to be essential in their biological activity. Two of the best characterized vitamin K dependent proteins is not involved in hemostasis or osteocalcin or bone Gla protein and matrix Gla protein. Supplementation with 1 mg per day of phylloquinone has been reported to return serum calcium of undercarboxylated osteocalcin to normal in postmenopausal females between 55 and 75 years of age. Vitamin K supplementation has lead to significant reductions in both urinary calcium and hydroxyproline excretion in the subgroup suggesting a decrease in bone resorption. Review of the overall observations related to vitamin K and osteoporosis include: 1. Low concentrations of circulating vitamin K in patients with bone fractures. 2. Concentrations of circulating under-gamma-carboxylated osteocalcin associated with age, low bone mineral density and hip fracture. 3. Anticoagulant therapy associated with decreased bone density. 4. Vitamin K supplementation decreases bone loss and calcium excretion. There are many unanswered questions. It may be that vitamin K in pharmacologic doses has an anti-resorptive effect and as such may be potentially utilized in the treatment or prevention of osteoporosis in some individuals. It is also plausible that vitamin K insufficiency is much more common than is currently thought and it does contribute to the pathogenesis of osteoporosis and fracture. Further research is needed. 22875 [end, nut] This study evaluated women with premature ovarian failure. Pregnancy occurred in these individuals in the absence of ovarian function. Concentrations of testosterone and androstenedione were very low if not lower than nonpregnant women. These concentrations were significantly increased in normal pregnancies and were even further increased in human menopausal gonadotrophin-treated cycles. This research shows that the ovary is a contributor to the circulating concentrations of testosterone and androstenedione starting within the cycle of conception. 22453 [rep] The director of the Bogalusa Heart Study is recommending universal cholesterol screening of children beginning at the age of 4 based on new findings. Selective screening results in underdetection of high cholesterol children. In evaluating over 8,000 children and their parents in the town of Bogalusa, it was found that parental evidence of cardiovascular disease rises as both children and their parents age (Circulation, 1995;91:365- 371). Offspring of parents who have a heart-attack history were significantly overweight after 10 years of age and showed elevated levels of total cholesterol, VLDL cholesterol, LDL cholesterol, insulin and glucose after 17 years of age regardless of their weight. Some of the researchers encourage looking not only for a family history of heart disease in the parents and grandparents, but also for all heart disease, especially premature heart disease or high cholesterol before the age of 55. The professor and chair in the Department of Epidemiology and Biostatistics at the University of California, San Francisco, Dr. Stephen B. Hulley, feels that cholesterol screening in children may do more harm than good. Psychologically having this "air" of adult disease and death hanging over them would be intense. They would be asked to eat differently from their peers at an age in which growing up is difficult enough. At best, universal childhood screening could be used as a "gentle one-time review" of risk factors and beneficial lifestyle. 21703 [car] This study evaluated the results of 14 controlled trials on the use of hyperbaric oxygen in multiple sclerosis. Eight trials were considered of reasonable high quality. In 1 of the 8 trials results favored hyperbaric oxygen treatment. The others had no clear effects. These patients had chronic progressive or chronic stable multiple sclerosis. In most of the trials hyperbaric oxygen was supplied at pressures of 1.75-2 ATA during 20 sessions of 90 minutes in 4 weeks. Side effects were generally minor but included ear and visual problems. Even though these trials showed little benefit further trials might be done in patients with disease of recent onset or with other dosing regimens. 22440 [neu] This study evaluated 2,710 Japanese Americans between the ages of 55 and 64 years who were free from evidence of coronary heart disease, cerebrovascular disease, cancer or aortic aneurysms. Among men studied 602 atherosclerotic events developed during the 23 year period of follow-up. After adjusting for variables significant positive associations between quartile cut offs of body mass index, systemic blood pressure, serum levels of cholesterol, triglycerides, glucose and uric acid, as well as cigarette smoking and the occurrence of any atherosclerotic end points were seen while an inverse association with alcohol consumption was observed. The results of this study provide additional support for risk factor modification in middle-aged men and for the encouragement of positive, long term lifestyle changes. 22447 [cad] This is an editorial on the role of pollution in asthma. There is little doubt that air pollution can increase the respiratory symptoms in the short and long term. Industrial pollution with sulfur dioxide and smoke does not cause asthma but appears to increase its severity. Diesel exhaust fumes and ozone can enhance the effects of inhaled allergens or have an effect on immune function. The rise in asthma prevalence has coincided with a fall in heavy industrial pollution but an increase in motor vehicle emissions. It is possible that air pollution causes asthma but this hypothesis is far from being proven. Newer pollutants such as ozone PM10 and diesel emissions are suspect. 22565 [all, pul] Under metabolic ward conditions, replacement of carbohydrates by lauric, myristic, and palmitic acids raises both low density lipoprotein cholesterol and high density lipoprotein cholesterol. Stearic acid has little effect. Oleic and linoleic acids raise HDL and slightly lower LDL cholesterol. In general, fatty acids lower fasting triglycerides when substituted for carbohydrates. Trans monounsaturated fatty acids lower HDL and raise LDL cholesterol and lipoprotein(a). Fatty acids that are from unhydrogenated fish oils potently lower triglycerides with variable effects on LDL cholesterol. Palm-kernel and coconut oils are the most hypercholesterolemic fats, followed by butter and palm oil. The replacement of the hard fats, or trans fatty acids, by unsaturated oils will lower LDL. Replacement by carbohydrates will, in addition, decrease HDL cholesterol and increase triglycerides. High oil diets may undo their positive effects on HDL cholesterol and triglycerides by leading to obesity. 21461 [car, nut] The authors note that many patients on high dose chemotherapy for lymphoma or myeloma test positive for prothrombin precursor PIVKA II. These are proteins induced by vitamin K absence or antagonism. The authors randomize patients who are undergoing autologous bone marrow transplantations received weekly 10 mg of intravenous vitamin K supplementation over the 4 week transplant period or to receive extra vitamin K. These specific proteins that are induced by vitamin K absence or antagonism were discovered in only 2 patients given vitamin K compared with 7 who did not receive the supplements. Patients who used vitamin K had dropped below the normal range after chemotherapy were maintained within or above this range after starting supplementation in contrast to the nonsupplemented individuals. Aberrations in vitamin K dependent anticoagulant protein C and S have been noted in patients receiving high dose chemotherapy for breast cancer. This may increase the risk of thrombosis. In patients not receiving vitamin K supplementation adequate production of hemostatic regulators was demonstrated by a fall in factor VII levels and in protein C levels shortly after bone marrow transplantation. Vitamin K administration began 1 week post transplant in the group receiving supplementation when patients had previously been noted to have the lowest plasma levels. By the 3rd week the mean change in factor VII level in the supplement group of a +15% was significantly different from the nonsupplemented group. The authors conclude that the stress of high dose chemotherapy may result in a temporary state of vitamin K deficiency. This vitamin K deficiency state may be prevented by weekly intravenous administration of 10 mg of vitamin K. 22404 [can] This study evaluated the relationship between blood pressure and RBC sodium and potassium concentrations in 1,805 men and women between 25 and 74 years of age. In men, RBC sodium concentrations were not significantly related to systolic or diastolic blood pressure while RBC potassium concentrations were significantly and inversely related to blood pressure. In women, RBC sodium values were significantly and directly correlated with systolic and diastolic blood pressure, but RBC potassium concentrations were not significantly related to blood pressure. In men there was a significant independent and inverse relationship of RBC potassium concentration with hypertension and blood pressure, and in women a significant positive association of RBC sodium concentrations with hypertension. RBC sodium did not relate independently to either systolic or diastolic blood pressure in men or women. The relationship between RBC potassium levels and blood pressure in men and the relationship between RBC sodium levels and hypertension in women was stronger in older individuals between 55 and 74 years than in the younger individuals between 25 and 54 years of age. The authors conclude that the association of RBC sodium and potassium concentrations and hypertension may be sex and age specific. Further studies are warranted. 21717 [car] This letter to the editor notes that there is a hypothesis that red wine phenolics can protect low-density lipoproteins against oxidative modification, thereby reducing the risk of cardiovascular disease. The authors looked at 24 healthy, non- smoking, normolipidemic volunteers who consumed white wine for 2 weeks. They were then randomly assigned to receive 550 ml per day, which is 4 to 5 glasses, of a white wine (Liore 1993) or a red wine (Italian Chianti Classico 1991) for 4 weeks. The subjects followed a flavonoid-poor diet and abstained from tea and red wine. No vitamins or minerals were taken. The oxidation rates and lag times, which indicate the resistance of LDL to oxidative modification, were similar in both wine groups. In contrast to previous research, the authors found that daily consumption of flavonoid-rich red wine did not influence oxidizabilty of LDL. These findings do not support the proposed beneficial effect of red wine consumption on LDL oxidation. 21728 [car] This study evaluated lactose malabsorption with respect to whole milk, skimmed milk, chocolate milk, sucrose, corn flakes, milk with Bifidobacterium organisms and 2% milk. Frozen concentrated cultures of lactobacillus acidophilus were obtained from 2 commercial sources. Ten men and 6 women between 26 and 45 years of age were involved in the study and they exhibited hydrogen breath tests of more than 20 parts per million over baseline after ingesting 360 ml of whole milk containing 18 gm of lactose. Usually an increase of more than 20 ppm is accepted as an indication of lactose malabsorption. Consumption of corn flakes completely alleviated lactose malabsorption as measured by the breath hydrogen testing with a concentration of less than 20 ppm. This was statistically significant. Chocolate milk and skimmed milk with added sucrose did not lower the breath hydrogen concentration to less than 20 ppm but did reduce total breath hydrogen production. Lactic cultures did not have any positive influence on lactose malabsorption. The effectiveness of corn flake consumption with whole milk is in accordance with other studies showing the effect of consumption of milk along with solid foods or meals. 22161 [gas] This study evaluated 97 middle ear infusions during myringotomy and tube placement for chronic otitis media with effusion of a duration greater than 3 months. All these patients had failed multiple courses of antibiotic therapy. Of the 97 specimens of otitis media with effusion 28 tested positive by both culture and PCR for M. catarrhalis, H influenza, or S. pneumoniae. An additional 48% of the specimens were PCR positive/culture negative for these 3 bacteria. Therefore, 77.3% of 97 specimens tested PCR positive for 1 or more of 3 tested organisms. The PCR-based assay can detect the presence of bacterial DNA in a significant percentage of culturally sterile middle ear effusions. This large number of bacterial genomic equivalents that are present in the ears suggest an active process of bacterial infection. This data suggests but does not prove that bacteria may be present in a greater percentage of otitis media with effusion specimens than previously thought. This data also influences the bacterial species and subtypes chosen for vaccine development. 22467 [oto, ped] In the United Kingdom the prevalence of celiac disease is approximately 1 in 2000. This disease peaks in early childhood between 2 and 3 years of age and also in adult life between 30 and 40 years of age. Almost twice as many adult women are diagnosed as men. The mucosal lesion in the small intestine impairs nutrient absorption. When wheat gliadins are eliminated or the equivalent barley, rye and oat prolaminins are withdrawn from the diet, the lesions and nutrient absorptions improve quickly. Patients may develop gastrointestinal symptoms or symptoms of nutritional deficiency. Weight loss, diarrhea and fatigue frequently occur. Occasionally rickets from vitamin D deficiency or bleeding from vitamin K deficiency occurs. The diagnosis of celiac disease is based on histologic findings in upper small intestinal biopsies and the response of the mucosa to a gluten-free diet. Villous atrophy, crypt hyperplasia and infiltration by inflammatory cells, particularly lymphocytes, return to normal after a gluten-free diet. A screening serum antibody test to gluten or one of its components or to reticulin or endomysium may be positive. These antibody tests can have high sensitivities and specificities in over 90%. There is a close association with dermatitis herpetiformis, a skin disease characterized by a symmetrical itchy, blistering eruption usually on the extensor surfaces of the elbows and forearms but also on the buttocks and knees. A lifelong gluten-free diet is the treatment of choice. Sometimes nutritional deficiencies such as iron, folate and vitamin B may need to be restored. Reasons that a gluten-free diet may fail may include continued ingestion of gluten, incorrect diagnosis, temporary lactose intolerance, other food intolerance (eg egg, chicken), zinc deficiency, concomitant bacterial overgrowth or pancreatic insufficiency. Complications of celiac disease include ulceration, stricture or malignancy. Gastrointestinal tract malignancy occurs in approximately 5% of celiac disease cases. Adherence to a gluten-free diet many times needs the experience of a dietitian. Initially there is weight gain due to improved absorption. Problems with a gluten-free diet include weight loss due to food reduction, constipation due to lack of consumption of fibrous foods, fear of eating, resentment from teenagers who often are unhappy with limitations and continued life-long follow-up. Other causes of small bowel abnormalities in the intestinal mucosa include cow's milk protein intolerance, soy protein intolerance, immunodeficiency syndrome, eosinophilic gastroenteropathy, intractable diarrhea of infancy, gastroenteritis in children, parasites, tuberculosis, HIV, contaminated bowel syndrome, Whipple's disease, tropical sprue, arterial disease of the small intestine and drug and radiation damage. 21362 [nut, car] This study evaluated 325 infants who died suddenly and unexpectedly and were diagnosed as having sudden infant death syndrome (SIDS). Data sets from 5,920 randomized controls were evaluated. Smoking during pregnancy was associated with a significant increased risk of SIDS of 2.7. There was a clear dose response relationship between the number of cigarettes smoked and the risk of SIDS. The risk of SIDS was almost doubled if the mothers not only smoked but were also anemic at less than 100 g/l of hemoglobin. These results support the concept that smoking during pregnancy has a direct biological effect on the fetus which is associated with an increased risk later on in life. Maternal smoking is an important modifiable risk factor for Sudden Infant Death Syndrome. 22166 [ped] In this review article it is concluded that intestinal dysmotility can result in bacterial overgrowth. Bacterial overgrowth may have an effect on digestion and absorption. Bacterial overgrowth may occur in patients with late radiation enteropathy. There is also a possibility that the bacterial overgrowth occurred first even though it is less likely. 22509 [gas] This study evaluated total homocysteine values in 26 healthy adults; 79 hospitalized patients whose serum vitamin B12 and folate and erythrocyte folic acid levels were greater than 230 pmol/l, 12 nmol/l and 600 nmol/l respectively; 32 hospitalized patients with serum vitamin B12 levels less than 147 pmol/l, compared to 25 patients whose serum vitamin B12 levels were greater than 147 pmol/l but unmatched in any other parameter; and 194 patients whose blood samples were sent for evaluation of vitamin B12 and folate from a neurological service. None of this later group had megaloblastic anemia. There was a relationship between elevated total homocysteine levels in the serum and low values of serum vitamin B12 and erythrocyte folic acid. This relationship was most significant when vitamin B12 levels were less than 86 pmol/L and erythrocyte folate was less than 335 nmol/L. There were some cases of elevated homocysteine in samples where the serum vitamin B12 and erythrocyte folic acid levels were greater than these. There was a poor correlation between serum folate and serum total homocysteine levels. There was a minimal correlation between neutrophil lobation and total serum homocysteine levels. 21566 [hem] This study evaluated 50 histologically confirmed cases of laryngeal cancer compared to 43 hospital and 46 population controls. The highest odds ratio corresponded to wood workers after adjusting for tobacco and alcohol consumption. The risk increased with the duration of exposure and decreased with the number of years elapsed since leaving it. The odds ratio for wood workers exposed over 20 years was 5.63, which is even greater than the furniture workers subgroup. Other high odds ratio occupations were transport drivers and brick layers and masons. Wood dust or chemical compounds used in the treatment of wood may be the strongest reason for the association found. 22785 [can] This study evaluated 41 nonpregnant females who gave birth to neural tube defect children and 50 control women who previously had normal offspring for homocysteine levels and for fasting blood levels of folate, B12 and B6. The mean values for basal homocysteine and homocysteine following a methionine load of 0.1 gm of L-methionine per kg body weight were significantly increased in the group of women who previously had had neural tube defect infants. In 9 of these subjects and 2 of the controls, the values after methionine ingestion exceeded the mean control by more than 2 standard deviations. These findings suggest a disorder in the remethylation of homocysteine to methionine due to an acquired nutritional or inherited abnormality in folate or vitamin B12 metabolism. Increased homocysteine levels can be normalized by the administration of vitamin B6 or folic acid. The authors recommend the prevention of neural tube defects by periconceptional folate administration which could effectively correct a mild to moderate hyperhomocysteinemia. The doses utilized of folic acid were between 4 mg and 5 mg. 21813 [neu, obs] This study evaluated 352 patients with colon cancer, 217 cases of rectal cancer and 512 controls. High coffee intake was negatively associated with the risk of colon cancer. The odds ratio for those drinking 6 or more cups of coffee per day was 0.55 compared to those drinking 1 or fewer. There was no association between rectal cancer and coffee consumption. For tea, there was no association with colon cancer, but there was an odds ratio for rectal cancer of 0.56 for those who drank 2 or more cups of tea per day. Those who smoked more than 11 cigarettes per day had a 20% to 30% reduction in the risk of colon and rectal cancer. In this population-based controlled study, normal coffee intake was associated with a decrease in colon cancer. Tea appears to have a protective effect against cancer of the rectum. There was no substantial association with cigarette smoking and the risk of cancer of the colon or rectum. 21588 [can] This study evaluated 25 patients with primary hyperoxaluria who had been treated over a 10 year period with orthophosphate and vitamin B6. Treatment with orthophosphate and vitamin B6 reduced urinary supersaturation with calcium oxalate from 8.3 to 2.1 kJ per mole. This therapy also increased inhibition of calcium oxalate formation from 63 to 108 inhibitor units per 24 hours and improved the crystalluria score from 2.6 to 0.6. The authors conclude that treatment of primary hyperoxaluria patients with orthophosphate and pyridoxine decreases urinary oxalate crystallization and preserves renal function. 21420 [nep, uro] Elevated homocysteine levels occur frequently in end stage renal disease. This study evaluated total fasting homocysteine, plasma levels of folic acid, pyridoxal 5'-phosphate, plasma vitamin B12 levels, serine, total cholesterol and HDL cholesterol, glucose, creatinine in 24 end stage renal disease patients on dialysis compared to 24 age-matched controls. Mean plasma homocysteine levels were considerably higher in end stage renal disease patients versus controls. End stage renal disease patients were 3 times more likely to have elevated homocysteine levels. These elevated homocysteine levels persisted in end stage renal disease patients despite normal to super normal B vitamin status. Plasma serine levels below the 10th percentile of the control distribution were found in 75% of the end stage renal disease patients. Oral L-serine was given in 3 or 4.5 gm tablets taken twice daily for a total of 3 gm in 1 patient and 4 gm in 3 patients for 7 days and then stopped. This resulted in a 37% increase in plasma serine levels but no effect on plasma homocysteine in 4 end stage renal disease patients with supernormal levels of plasma serine and hyperhomocysteinemia. It is possible that reducing hyperhomocysteinemia might reduce cardiovascular consequences of end stage renal disease. Supplementation trials need to be done to confirm this. 22221 [car, nep] Thirty-three healthy term infants were given either a soy formula or a soy formula with added selenate at approximately 0.17 umol Se/L. Those who had the soy formula with the selenium had significantly higher plasma and erythrocyte selenium concentrations and glutathione peroxidase activity than those fed the soy formula only. The addition of selenate to the soy formula resulted in selenium intakes that were similar to the 10 ug Se/d in 1989 RDAs for infants between 0 and 6 months of age. 21626 [nut, ped] In a rat model carnitine administration given by intraperitoneal injection to 21 day old rats prevented the increase of thiobarbituric acid-reactive substances which were induced by 30 minutes of hypobaric hypoxia in the cerebral cortex, subcortical structures, medulla oblongata and cerebellum. 22318 [neu] This is a case report of a 46-year-old female with a 6 month history of recurrent erosions in the mouth. She had been treated previously with amphotericin and Acyclovir without results. She was diagnosed as having pemphigus vegetans which is a rare clinical variant of pemphigus which accounts for 1 to 2% of all the cases of pemphigus. In this type of pemphigus the oral mucosa is often effected and the tongue has a "cerebriform appearance". This patient also had esophageal mucosal lesions. The patient was treated with a combination of minocycline 100 mg a day and nicotinamide 1500 mg a day which resulted in complete resolution of the erosive vegetating lesions on the lips and perianal region within a week. The oral mucosal lesions also regressed. She has received this combination therapy for 10 months and her disease remains in remission. 22224 [der] This is a review article on the role of nitric oxide and arginine in sepsis. Nitric oxide is an unstable free radical. Nitric oxide is produced by the five-electron oxidation of 1 of the 2 equivalent guanidino nitrogens of L-arginine. It has been noted since 1981 that infections cause increased nitrate and nitrite production in man. Nitric oxide is a potent effector molecule in multiple biochemical pathways associated with sepsis in humans and in other mammals. Its functions include cytotoxicity for bacteria, fungi, and parasites, support of chemotaxis, inhibition of platelet aggregation and thrombosis, and free radical detoxification. It also mediates the hypotension of septic shock. During sepsis nitric oxide is produced through a variety of inflammatory cytokines. The induction of nitric oxide synthesis increases demand for arginine in a variety of cell types such as vascular endothelial cells, macrophages and hepatocytes. These cells respond by increasing arginine uptake and synthesis. 22616 [met] This study evaluated 28 subjects with the diagnosis of simple phobia compared to 30 normal controls who were subjected to a 35% carbon dioxide panic provocation. The phobic patients reacted more strongly to the challenge of carbon dioxide than the contro7ls. This increase in anxiety was comparable to the increase of anxiety of panic disorder patients from other studies. The authors conclude that there is a constitutional þpredispositionþ that may lead to panic disorder and to the development of specific phobias. Through a self-administering apparatus subjects received, in a random order, a 7-vital-capacity breath of 35% C02/65% 02 mixture and an 80% N2/20% O2 mixture. Between the 2 inhalations the subjects had a 15 minute break outside the laboratory. It appears possible to use this test to help understand the underlying mechanisms in different anxiety disorders. 21480 [psy]7 One hundred eighty-four premature infants who were less than 1800 gm at birth and less than 36 weeks age of gestation were studied for the effects of folate and vitamin B12 supplementation on the anemia of prematurity. Four randomly selected groups received either 0.1 mg of folic acid per day for four months, 100 mcg of vitamin B12 intramuscularly monthly for four months, both supplements, or neither. At the end of 10-12 weeks, infants treated with vitamin B12 alone or in combination with folate had higher hemoglobin values than the untreated or the folate only treated groups. The uncontrolled hematologic factors selenium and glutathione peroxidase were unaffected by the nutritional supplementation. Both of these substances decreased through the first 12 weeks of age. At 6 months the selenium concentration had risen slightly whereas glutathione peroxidase concentrations remained low. Further research needs to be done on the role of selenium and glutathione peroxidase in relation to other nutritional factors that are necessary for optimal red blood cell metabolism in premature infants. 21455 [hem, nut, ped] This study evaluated 185 patients with a history of recurrent venous thrombosis in 220 controls for the general population. Homocysteine concentrations were measured before and 6 hours after an oral methionine load of .1 gm of elemental methionine per kg body weight. Hyperhomocysteinemia was defined as homocysteine concentrations above the fasting or the post-methionine value for the 90th percentile of controls. Of 185 patients with recurrent thrombosis 25% had fasting homocysteine concentrations above the 90th percentile or the controls. After adjusting for variables the odds ratio was 2.0. A similar result was found for the post methionine value with an odds adjusted ratio for 2.6. The authors conclude that hyperhomocysteinemia is a common risk factor for recurrent venous thrombosis and can lead to a 2 to 3-fold increased risk. The underlying mechanism by which hyperhomocysteinemia can cause thrombosis is unknown. There is some evidence that homocysteine contributes to endothelial damage in the arterial vessel but it is not clear. Another mechanism may be the in vitro effect of homocysteine on factor V activation and inhibition of thrombomodulin dependent protein C activation. There may be a thrombocyte aggregatory component caused by homocysteine. Elevated homocysteine may result from a hereditary defect in enzymes involved in methionine metabolism or it may be due to a vitamin deficiency. The authors did not find lower levels of folic acid or vitamin B12 in patients more than controls. In fact, higher homocysteine concentrations at a given folic acid concentration were found in patients than in the controls. This may suggest that some form of decreased enzyme activity and not vitamin deficiency leads to thrombosis. Several studies have shown that vitamin supplementation can lower homocysteine levels. Whether vitamin supplementation for those high values of homocysteine will be beneficial with respect to prevention or venous thrombosis has to be further studied. 22141 [car] This was a prospective study of 40 uremic non-responders to one complete hepatitis B vaccination cycle underwent a second hepatitis B vaccination. In 28 of these patients, zinc substitution was given which was 60 mg of zincaspartate given intravenously in a short infusion after each hemodialysis, which was 3 times per week for 4 months. This was 2 months before the vaccination and 2 months after. The chronic uremic patients showed subnormal predialysis plasma zinc concentrations compared to the healthy controls. In the zinc treated patients, plasma zinc concentrations increased and were maintained during the treatment. After the hepatitis vaccination, a seroconversion was seen of 5 of 28 zinc treated subjects and 2 of 12 controls. This was not a significant difference between the 2 groups. The authors conclude that the diminished response to hepatitis B vaccination in chronic uremic patients is refractory to zinc supplementation. 21798 [inf, nep] Out of 487 patients studied, 106 women were antibody positive for anti-TG or antithyroid peroxidase antibodies or both, and 381 were negative. The overall incidence was a positivity of 22%. In the antibody positive group there was a 32% clinical miscarriage rate in comparison to 16% in the antibody negative group. There was no significant difference between the 2 groups in the incidence of biochemical or ectopic pregnancies. There was no significant difference between groups in age, gravidity or number of prior pregnancy losses. In this study, thyroid antibodies served as a useful marker for identifying women at risk for clinical miscarriage, but they appear not to have an association with biochemical pregnancies. 21993 [all, end, gyn, obs] This study found that children whose mothers received 100 mg per day of elemental iron during pregnancy, regardless of their iron status, had a increased risk of hospitalizations for convulsions compared to mothers who received iron supplementation only if they were anemic. Prenatal exposure to iron appears to cause the child's brain to be more susceptible to injury or increases the risk of infections which have seizures as a complication. One thousand three hundred and thirty patients began taking daily iron supplements no later than the 17th week of pregnancy; compliance rate was 84%. The remaining 1,352 women took supplemental iron only if their hemoglobin fell to less than 10 g/dl. The incidence of hospitalization for convulsions was 2.4% among children born to mothers who took iron whether they were anemic or not, compared to 1% in the group whose mothers took the iron only if they were anemic. This population was a group of well nourished women. 21376 [neu, obs] This was a 1 year prospective study evaluating 266 female and 59 male community dwelling volunteers ages 60 to 93 years who had fallen at least once during the previous year. Frail individuals were more than twice as likely to fall as vigorous individuals. Falls were not strongly associated with the presence of home hazards. Vigorous older persons living with more hazards were more likely to fall than vigorous individuals with lesser hazards. In frail individuals living with more home hazards was not associated with an increased likelihood of falls. Vigorous older individuals should not overlook fall prevention projects. 22748 [ger, ost] This study evaluated the relationship between insulin and weight gain in a prospective study in 97 Pima Indians with normal glucose tolerance. During a mean follow-up period of more than 3 years the average weight increased 2.1% per year in males and 3.5% per year in females. This reflects an annual increase in body fat content of 6.9% per year in both sexes. Insulin secretion was negatively associated with the rate of weight gain. The significance of the relationship between each measure of insulin secretion and weight gain persisted after controlling for variables. Slightly reduced insulin secretion is a significant and independent predictor of the tendency to gain weigh and adiposity in Pima Indians. The presence of relative insulin resistance also conferred an independent reduction in the risk of weight gain in some regression analysis. The authors conclude that insulin resistance and hyperinsulinemia are unlikely to play a causal role in the development of obesity. Relatively reduced insulin secretion is a marker of an increased risk of weight gain in this population. This data supports the hypothesis that the level of insulin secretion plays an important role in long term weight regulation. Relatively reduced insulin secretion contributes to the progression of both obesity and glucose intolerance in subjects who bear the thrifty "genotype", which progresses to overt B-cell failure and non insulin dependent diabetes mellitus. 22685 [end] This study evaluated 96 children of which 58 were boys and 38 were girls. A total of 713 days of food diaries were collected with a mean of 7.4 days per child. A total of 1,057 foods containing caffeine were identified on food diaries and were classified into 6 categories which included soft drinks, tea, baked goods, dairy beverages, candy, and desserts. In the last 4 categories caffeine came from chocolate contained in the foods. None of the children consumed coffee. The mean ages of the boys were 8.4 years and the girls were 8.1 years. The boys consumed more caffeine than girls (17 mg/d vs 14.4 mg/d). Even when adjusting for increases in body weight caffeine consumption tended to increase with age averaging .44, .46, .53 and .68 mg/kg per day for the 4 age groups respectively. Caffeinated soft drinks and chocolate contained almost all the caffeine. Approximately 55% from soft drinks and 38% from chocolate. Baked goods contained 17%, dairy beverages 11%, candy 5% and dairy desserts 5%. Only 7.6% of the caffeine was obtained from tea and then from coffee. The major source of caffeine in our study was caffeinated soft drinks. Soft drinks provide about 26% of the caffeine, but tea was the larger source. This data suggests that the levels of caffeine intake in young children may be less than previously thought. The intake of caffeine from soft drinks and chocolate-containing foods by children in this study was similar to that of previous reports. Consumption of tea and coffee by these children was minimal. Regional patterns of caffeine- containing foods, especially tea and coffee, should be taken into consideration when evaluating caffeine intake. 22794 [nut] This study evaluated over 6,600 English and Spanish speaking adults between 18 and 64 years of age from 41 different areas about their access to health care, their chronic medical conditions and their likelihood of seeking health care. Access to health care was inversely associated with hospitalization rates for 5 chronic medical conditions. These included weight loss of more than 10 pounds without dieting, shortness of breath with light exercise or light work, chest pain when exercising, loss of consciousness, fainting or passing out and bleeding other than nosebleeds not caused by accident or injury. Communities which have poor access to medical care have high rates of hospitalization for chronic diseases. Hospitalization rates may serve as an indicator of access to health care and health outcomes in evaluations of programs and policies. 22910 [med] Twenty patients with long term sporadic Alzheimer's disease received vitamin supplementation of iron, B6 and coenzyme Q10. There was a significant improvement in a variety of mental and functional tests at one year. It is believed that coenzyme Q10 might reduce the free radicals formed by iron, and that B6 plays a role in neurotransmitter synthesis. The combination of these 3 may have a positive effect on reducing the signs and symptoms of Alzheimer's disease. 21436 [ger, neu, nut, psy] This study evaluated 152 individuals, 26 to 65 years of age, for the relationship between antioxidants and coronary heart disease. Lower plasma vitamin E, beta-carotene and higher lipid peroxides were found in those patients with coronary artery disease versus those without risk factors. Dietary intake of vitamins A, C, E and beta-carotene were significantly more in patients without CAD. Smokers and diabetics consume less vitamin C and beta- carotene than their control group counterparts. 21829 [car] Because of the increased risk of becoming infected with salmonella bacteria, pregnant women, children under the age of 2 and people with depressed immune systems should avoid contact with reptiles. Since 1994 health departments in 13 states reported cases of salmonella infection in which people had direct or indirect contact with reptiles including lizards, snakes or turtles. In some cases the infection resulted in serious illness such as meningitis or sepsis. Reptiles are popular pets in the United States. There is about 7.3 million reptiles owned by about 3% of the U.S. households, according to the Center for Disease Control. In most cases the bacteria are transmitted to humans when they come in contact with the animal's feces. 22592 [bac] Eating foods of plant origin result in low rates of chronic disease and long life expectancies. Research shows that an increase of vegetable, fruit and fiber consumption are associated with lower rates of cancer, coronary heart disease, neural tube defects and cataracts. Carotenoids, folic acid and fiber appear to be all abundant in the Mediterranean diet and play a role in preventing these diseases. There is evidence that a high consumption of full- fat dairy products increases the risk to coronary heart disease. Epidemiologic data does not show that high diary product consumption prevents fractures. Several studies have shown an opposite effect. The authors conclude that the abundant fruit and vegetable and whole grains and low to moderate intake of dairy products in the traditional Mediterranean diet are likely to contribute to the low rates of chronic, degenerative diseases that are seen in this population. 22552 [can, car, end, neu, ost] High intensity strength training may reduce a postmenopausal woman's risk for osteoporotic fracture. Such training is protective on bone mineral density and promotes increased muscle mass, strength, dynamic balance and overall activity levels in postmenopausal women. This is the first time that a single program has shown to affect so many different risk factors for osteoporosis. In this study women trained on pneumatic machines. However, a home-based strength training program, using inexpensive dumbbells or water filled milk containers, may also give benefit. The strengthening program is feasible for frail individuals; it may significantly improve strength, mobility and functional status without risk to subjects. In this study, 39 white, sedentary, postmenopausal women were randomized to an exercise training group and a control group. Women in the exercise group participated in high intensity strength training 2 days per week for a year. Pneumatic resistance machines were used; exercises included hip extensions, knee extensions, lateral pull-downs, back extensions and abdominal flexion. At the end of the study femoral neck bone mineral density and lumbar spine density in the strength-trained women had increased 1.0%. In the controls femoral neck bone mineral decreased by 2.5% and lumbar spine bone mineral density decreased by 1.8%. The total body mineral content was preserved in the strength trained women, but a decrease of 1.2% was seen among women in the control group. Total body muscle mass, muscle strength and dynamic balance increased in the strength trained women and decreased in the controls. Women who exercised increased their energy expenditure and activities exclusive of the intervention by 27%. Controls decreased their spontaneous activity by 25%. 21897 [ort] A 3 day meeting at the Federal Office of Alternative Medicine in the Food and Drug Administration reviewed how to determine the safety and effectiveness of botanical treatments. Botanicals are classified as dietary supplements in the United States and sold mainly in health food stores. They are not allowed to advertise specific health claims. The new dietary supplement act allows companies to use objective articles and reputable books and journals that discuss their products as long as they do not mention a brand name. The purpose of the meeting was to put skeptics and believers together in a forum to discuss the range of necessary scientific and regulatory goals that need to be met for botanicals. Botanicals have received more attention since the government opened The Office of Alternative Medicine at the National Institutes of Health in 1992. Another reason for the current interest in botanicals is to lower health care costs. For example, botanicals can be used to treat migraine headaches at 10 to 25› per day, compared to $2.00 to $8.00 for an ordinary prescription per day. Coated garlic tablets, which have been reported to lower cholesterol, can cost 15› per day compared to $4.00 for a daily dose of a prescription drug. It is noted that no really new therapies have been developed for any of the major forms of cancer over the last 2 decades. Therefore it is hoped that botanicals, which have proven successful in treating other ailments, may provide some light in the otherwise-dark cancer tunnel. 21633 [can, car, her, nut] This study evaluated 97 middle ear infusions during myringotomy and tube placement for chronic otitis media with effusion of a duration greater than 3 months. All these patients had failed multiple courses of antibiotic therapy. Of the 97 specimens of otitis media with effusion 28 tested positive by both culture and PCR for M. catarrhalis, H influenza, or S. pneumoniae. An additional 48% of the specimens were PCR positive/culture negative for these 3 bacteria. Therefore, 77.3% of 97 specimens tested PCR positive for 1 or more of 3 tested organisms. The PCR-based assay can detect the presence of bacterial DNA in a significant percentage of culturally sterile middle ear effusions. This large number of bacterial genomic equivalents that are present in the ears suggest an active process of bacterial infection. This data suggests but does not prove that bacteria may be present in a greater percentage of otitis media with effusion specimens than previously thought. This data also influences the bacterial species and subtypes chosen for vaccine development. 22467 [oto, ped] Studies of nineteen western European and five non-European countries showed premature mortality from coronary heart disease in men below the age of 65, related to food, antioxidant vitamins and other nutrient supply data, between 1985 and 1987. The phenolic antioxidant-rich foods such as wine, vegetables, and vegetable oils were inversely related to coronary heart disease. The alpha- tocopherol component of vitamin E was strongly related to coronary heart disease across Europe. The major determinant of alpha- tocopherol supply was usually sunflower seed oil. Vitamin C and beta-carotene gave moderate correlations. For the majority of countries, there was an inverse association between the supply of vitamin E and coronary heart disease. The authors conclude that vitamin E may provide just as good an explanation as wine for the paradoxically low rates of coronary heart disease in several European countries which have relatively high saturated fat intakes. 21732 [car] Nine healthy individuals were supplemented with 316 mmol of magnesium per day for 30 days. Total magnesium levels did not change throughout the whole time of the experiment. Ionizable magnesium decreased during the first 10 days and bound magnesium tended to increase. Ionizable magnesium and not calcium was positively associated with parathyroid hormone. On day 0 calcium and ionized magnesium correlated with parathyroid levels. Both of these correlations vanished after magnesium supplementation. By keeping the levels of parathyroid hormone down, it ensures that supplemented magnesium enters the bone and is not liberated along with calcium by possibly increased parathyroid levels, triggered by high circulating magnesium concentrations. 22024 [nut] This article reviews the suggestion that cancer may be reduced by antioxidants found in fruits and vegetables. The author concludes, in this extensive review, that even though eating fruits and vegetables appears to reduce the risk of getting cancer, the role of antioxidants in the protection of cancer is still unproven. Antioxidant nutrients reviewed include beta- carotene, vitamin C, E, selenium and zinc. 22003 [can] This study evaluated 33 estrogen-deficient postmenopausal females with a mean age of 59 years to determine if short-term estrogen replacement therapy also improves endothelium-dependent vasodilation in peripheral circulation. Acute intra-arterial infusion of estradiol, which increased forearm venous estradiol levels, potentiated forearm vasodilation induced by the endothelium-dependent vasodilator acetylcholine. The estradiol infusion also potentiated vasodilation induced by the endothelium-independent vasodilator nitroprusside. After 3 weeks of transdermal estradiol administration at 0.1 mg per day, the vasodilator responses to acetylcholine and to sodium nitroprusside were unchanged from initial measurements taken before administration of estradiol. In 8 women receiving transdermal estradiol, a repeat intra-arterial infusion of estradiol increased forearm venous estradiol levels and again potentiated vasodilator response of acetylcholine. The authors note that although acute intra-arterial infusion of 17B-estradiol potentiates endothelium-dependent vasodilation in the forearms of postmenopausal women, this effect is not maintained with a 3-week cycle of systemic estradiol administration. The different effects of acute and chronic estradiol may be due to the lower plasma levels achieved with chronic administration of the medication. Other long-term antiatherogenic effects of estrogen may result in preservation of endothelial function. 21759 [car, gyn] This was a multi-center, placebo-controlled, randomized trial testing the efficacy of fish oil in patients with IgA nephropathy who had persistent proteinuria. The daily dose of fish oil was 12 gm while the placebo was olive oil. Fifty-five received the fish oil and 51 received the olive oil. Six percent of the patients in the fish oil group versus 33% in the placebo group had increases of 50% or more in their serum creatinine during the treatment. The annual median changes in serum creatinine concentrations were considerably lower than in the placebo group. Proteinuria was slightly reduced and hypertension was controlled to a comparable degree in both groups. The cumulative percentage of patients who died were at end stage renal diseases 40% in the percent in placebo group after 4 years and 10% in the fish oil group. No patient discontinued the fish oil due to adverse side effects. The authors conclude that patient with IgA nephropathy treated with fish oil for 2 years retards the rate at which renal function is lost. 22396 [nep] This editorial notes that tobacco leaves contain significant amounts of cadmium. There is evidence that cadmium in tobacco reaches the lens of the eye. It has been shown that cataract lenses from smokers contain much more cadmium than those from nonsmokers. Smokers with or without cataract have higher cadmium levels in their blood. Smokers have lower levels of vitamin C, E and beta-carotene which lower plasma levels of vitamin C, E and beta-carotene which may explain the increased risk to the development of cataracts. In a recent study there was no decreased levels of vitamin C in smokers among either cataract or non-cataract populations nor was there a decreased level of vitamin C in the cataract lens of smokers. These results make it less likely that the causal pathway for smoking to cataracts is via vitamin C. A study by Ramakrishnan favors the idea that cadmium accumulation in the lens directly causes the damage. Other components in tobacco smoke may play a role. Cyanide and thiocyanate levels are raised in the blood of smokers and cigarette smoke is rich in free radicals and aldehydes. These radicals may cause or damage before reaching the lens but isocyanate from cyanide and aldehydes might find their way to the lens to attack the enzymes and other proteins. Isocyanate can cause lens opacification in vitro. Both aldehydes and isocyanate can modify lens proteins causing changes similar to those seen in human cataracts. If cadmium plays a major role in linking smoking to cataract then workers exposed to high cadmium levels in the cadmium plated steel industry, or those consuming cadmium rich food, such as rice in parts of Japan, might have an increased risk of cataract. 22111 [oph] This study evaluated the erythrocyte pyridoxal 5'-phosphate concentration and erythrocyte aspartate aminotransferase basal activity and its activation coefficient (alphaEAST) in 109 infants at 2, 4, 6, 9 and 12 months of age. Thirty-six of these children were exclusively breast fed for 9 months. Forty-six infants were exclusively breast fed for 6 months and then given solid food. Twenty-seven were weaned between 2 and 3 months to a cow milk-based formula and given solids from 3 to 4 months. Infant vitamin B6 status was age dependent. It was highest at 4 months and thereafter gradually approached adult values. The larger the intake of formula the higher the vitamin B6 status. In the formula fed infants between 2 and 6 months of age, 71-96% of the erythrocyte pyridoxal 5'-phosphate concentrations and 57-70% of the erythrocyte aspartate amino transferase basal activity values were above the 95th percentile; 35-53% of the alpha erythrocyte aspartate amino transferase basal activity was below the 5th percentile in breast fed infants. These results question the possibility that vitamin B6 content of formulas should be reduced. 21454 [nut, ped] Sixty-seven patients greater than 70 years of age admitted to a hospital with acute conditions were followed until death or hospital discharge. Patients with serum albumin concentrations less than 35 g/L showed a lower triiodothyronine (T3), a higher reversed triiodothyronine (rT3) concentrations and a higher death rate. Prior weight loss of greater than 10% did not affect thyroid status but increased the mortality rate. Eleven patients were hypothermic at less than 36.5ø C and a higher mortality, lower total T3 concentration and a higher reversed T3 concentration than normothermic or hypothermic patients. Serum albumin, body weight and total T3 concentrations were higher in 51 survivors than in the 16 nonsurvivors. A continued weight loss and hypoalbuminemia at admission are highly prevalent in elderly subjects with acute disease and can influence their clinical outcome. Mild hypothermia is a good predictor of death. Hypoalbuminemia and hypothermia were associated with low T3 and low rT3 values. 22373 [end, ger, hos] The cholesterol lowering effect of soy protein has been documented in many species even though it is not understood. This study evaluates the relationship between dietary protein sources and plasma thyroxine concentrations. The theory is that soy protein lowers plasma cholesterol by increasing plasma thyroxine concentrations. Animal studies show that feeding soy protein to laboratory animals consistently elevates plasma thyroxine concentrations. Elevation in plasma thyroxine concentrations comes before changes in plasma cholesterol concentrations which is important to produce a causative effect. It is concluded that there is consistent evidence that dietary protein can increase T4 levels. 22634 [car, end] This article reviews different ways to assess vitamin B12 deficiency. It is noted that the cellular metabolites methylmalonic acid and homocysteine accumulate during cobalamin deficiency. Transcobalamins are markers for cobalamin deficiency. An elevated methylmalonic acid level that is reduced with injections of cobalamin suggest "overt metabolic" vitamin B12 deficiency. This applies also to plasma homocysteine levels but it is less specific for vitamin B12 deficiency than methylmalonic acid. Vitamin B12 assays or methylmalonic acid are good screening tests for vitamin B12 deficiency. Causes of vitamin B12 deficiency include vegan diets, vitamin B12 malabsorption (occurs more frequently with age due to inadequate intrinsic factor), and inborn errors of metabolism, such as lack of transcobalamin (a plasma protein needed to transport cobalamin to the cells). Cobalamin absorption tests such as the Schilling Test are considered of limited value. Gastric atrophy is probably present in patients with increased gastrin or decreased pepsinogen. Vitamin B12 deficiency is not a rare disorder. Vitamin B12 deficiency is considered to be a common condition which presents most frequently as a broad spectrum of uncharacteristic symptoms such as vague neurologic complaints. There is much knowledge about the uptake and transport of vitamin B12 into the cells but there is a limited knowledge of the intracellular metabolism of vitamin B12. To understand cobalamin deficiency more fully, studies of the intracellular pathways of cobalamin and the intracellular enzymes utilizing vitamin B12 as cofactors will be needed. Once vitamin B12 deficiency has been diagnosed, the cause of the deficiency should be found and the patient should be treated for life. 21635 [hem, neu, nut] This study evaluated 30 patients with severe congestive heart failure who had received furosemide in doses of 80 mg per day or more for at least 3 months in a randomized, 1 week, double-blind, inpatient therapy with either IV thiamine at 200 mg per day or placebo. All other previous drugs were continued. Following discharge all 30 patients received oral thiamine at 200 mg per day as outpatients for 6 weeks. Thiamine-pyrophosphate effect, diuresis and left ventricular ejection fraction were unchanged after IV placebo. After IV thiamine the thiamine-pyrophosphate effect decreased from 11.7% to 5.4%. The left ventricular ejection fraction increased from .28 to .32 and diuresis increased from 1731 to 2389 mL/d and the sodium excretion increased from 84 mEq to 116 mEq per day. In 27 patients completing the full 7 week intervention left ventricular ejection fraction rose by 22%. The authors conclude that thiamine repletion can improve ventricular function and the biochemical signs of thiamine deficiency in patients with moderate to severe congestive heart failure who on long term furosemide therapy. The data suggests that thiamine supplementation corrected a subclinical state of thiamine deficiency. The authors concluded that thiamine supplements are beneficial adjuvants to conventional treatment in some patients with moderate to severe heart failure who have received long term therapy with furosemide. This is a simple and cheap, safe drug and it may improve elements of left ventricular systolic dysfunction and decreased functional capacity which are not only due to the heart disease itself but also to unsuspected thiamine deficiency. 22405 [can] Out of every 10,000 hospital admissions 7 to 21 are admitted for renal stone disease and close to 80% of the kidney stones are composed mainly of calcium oxalate. Regular black tea is known to have high oxalate concentrations and its consumption without adding milk has been shown to increase urinary oxalate concentrations. Herbal teas often contain ingredients that are known to contain oxalate such as citrus peels, berries and leaves. This study measured oxalate concentrations of herbal teas to determine whether herbal teas would be an acceptable alternative to reduce the risk to calcium oxalate stones. The oxalate content of herbal teas and coffee ranged from 7 to 32 times less than black tea. The green oolong tea measured in this study contained 1.5 to 3 times less oxalate than black tea steeped for 5 minutes. The difference has to do with the concentrations between green tea and black tea in the tea bag. When expressed oxalate per gram of tea oxalate levels in the green tea were similar to brands of black tea and half concentrations of the other. When black teas were steeped for 1 minute the oxalate content was less than when steeped for 5 minutes. Vigorous stirring of tea steeped for 1 minute caused a marked increase in oxalate concentration. Fourteen commonly available herbal teas that were infused for 5 minutes had low oxalate content even when compared to black tea that was only infused for 1 minute. Coffee prepared from the drip method was also found to have a low oxalate content similar to that of herbal tea. These may be reasonable alternatives for those with a history of calcium oxalate formation. 22264 [nep] By evaluating food frequency questionnaires and medical histories of 76 girls and 51 boys, a relationship between diet and fractures was shown. There was a strong association between cola beverage consumption and bone fractures in the females. A high intake of dietary calcium was protective. There was no association between non cola drinks and bone fractures found. In boys only total caloric intake was inversely associated with the risk of bone fractures. The authors conclude that a high consumption of carbonated beverages and the declining consumption of milk are a significant health risk for girls and women because of the increased risk to osteoporosis in later life. The soft drinks of particular concern are the cola drinks which contain phosphoric acid. Peak bone mass is a significant determinate of osteoporosis in later life. Osteoporotic fractures may be delayed by a change in diet and activity among young women. In one study, by the age of 16 years daughters had accumulated 90 to 97% of the bone mass of their premenopausal mothers. The consumption of carbonated beverages is estimated to be as much as 40 gallons per year per person. In conjunction with the declining consumption of milk, this may increase the risk to osteoporosis in later years. 21543 [ort] This article reviews the potential hepatotoxic effects of herbal medicine, including observed cases of hepatitis from ingestion of germander (Teucrium chamaedrys). Toxicity of pyrrolizidine alkaloids was recognized over 40 years ago. In Africa and Central America intoxication can be endemic since these plants are often used for tea making. In western countries cases of herb-induced hepatitis have been observed after the consumption of preparations containing Symphytum or Chinese herbs. Pyrrolizidine alkaloids cause obstruction of the hepatic venous system and can lead to hepatonecrosis. The prognosis is poor with a death rate of 20 to 30%. Signs and symptoms include abdominal pain, ascites, hepatomegaly and raised serum transaminase enzymes. Another example of herbal toxicity is Atractylis gummifera which includes 26 species that are used for medicinal purposes or for chewing gum. Toxicity usually occurs in the spring and is related to chewing the roots of these plants. Severe hepatocellular lysis can occur in less than 24 hours. Signs and symptoms include hypoglycemia and neurovegetative disorders or subsequent renal failure. These compounds can be effective inhibitors of the Krebs cycle and can lead to severe or fatal liver failure. Other cases resulting in fatal liver accidents have been reported after ingesting Callilepis laureola, an herb which is used by the Zoulous in Natal for medicinal purposes. Extracts of Teucrium chamaedrys, which have been used in France for weight loss, have also resulted in fatal liver events. The authors emphasize that herbal medicines are not harmless. Because of the distribution of many herbal preparations and the risk of self-medication, consumers and clinicians should be vigilant about the potentially hepatotoxic risk. 21410 [tox] Fatty acids with 2 or more unsaturated sites and chain links of 18- 22 were found to be potent inhibitors, in general, of leukotriene B4 binding. Both omega-3 and omega-6 fatty acids were inhibitory. In an in vivo model of leukotriene B4-induced bronchoconstriction, ricinelaidic acid was inhibited by 46% and homogammalinolenic acid by 53%. This was 1 mg/kg IV. The data suggests that essential fatty acids are leukotriene B4 receptor antagonists, which may account, in part, for their anti-inflammatory effects. 22525 [inf] Cigarette smoke contains oxidants as well as several precarcinogens. Metabolism of carcinogens and the steps of carcinogenesis are a balance between forces such as metabolic activation and detoxification, formation and scavenging of radicals and DNA damage and repair. This suggests that carcinogenic compounds can initiate tumor growth only when they saturate detoxification pathways. Glutathione plays a role in the detoxification of xenobiotics. N-acetylcysteine which is an amino thiol and precursor of intracellular cysteine and glutathione has been shown not only to be an efficient antidote in acetaminophen poisoning but also has important chemopreventive properties. N-acetylcysteine appears to exert its chemopreventive effects by multiple mechanisms and may provide protection against different mutagens and carcinogens in different stages of carcinogenesis. N-acetylcysteine has reached the Phase III trial stage in chemoprevention in Europe and has been used in clinical practice for more than 30 years. In large groups of patients with chronic obstructive lung disease N- acetylcysteine has turned out to be a safe agent with minor effects even when prescribed for a prolonged period of time. N- acetylcysteine is well tolerated when taken continuously in a dose of 600 mg per day. Dyspepsia has been reported as a mild side effect. N-acetylcysteine holds promise and it may turn out to be effective in preventing secondary tumors. It may have a wider use in chemopreventive purposes. 22777 [can] In evaluating over 21,000 children who were visited every 4 months over 2 years and in a morbidity study of 1,455 children who were visited weekly for 1 year, there was no difference between the children supplemented with vitamin A and those who were given a placebo in malaria mortality rates or fever incidence based on reported symptoms. There was no correlation between serum retinol at the beginning of the trial and subsequent malaria parasitemia in children receiving placebo. Vitamin A supplementation had no effect on malaria in this population. 22101 [inf] Sixteen hundred and eighty-seven women with eclampsia were recruited into an international, multi-center, randomized trial comparing standard anticonvulsant regimens. Four hundred and fifty-three were given magnesium sulfate at a dose of 4 gm initially over 5 minutes except for the centers in South America which gave 5 gm followed by an infusion of 1 gm per hour for 24 hours. Two to 4 gm were given IV over 5 minutes if the convulsions recurred. Intramuscular injections of 5 gm into each buttock after the loading dose with 5 gm I.M. given every 4 hours if the respiratory rate was greater than 16 per minute, urinary output greater than 25 mL per hour and the presence of knee jerks. The diazepam therapy was a loading dose of 10 mg IV over 2 minutes repeated if convulsions reoccurred and followed by an intravenous infusion of 40 mg and 500 ml of normal saline for 24 hours. The rate of infusion was titrated against the level of consciousness with the aim of overcoming restlessness and keeping the woman sedated but rousable. During the next 24 hours infusion of 20 mg of diazepam in 500 ml normal saline was to be given and slowly reduced. A third regimen was phenytoin. Ten mg of Diazepam was given IV with an additional loading dose of 1 gm IV of phenytoin by slow infusion over 20 minutes. This was followed by 100 mg every 6 hours for the next 24 hours. Women who received the magnesium sulfate had a 52% lower risk of recurrent convulsions than those given the diazepam and 67% lower risk of recurrent convulsions than those given the phenytoin. Maternal mortality was not significantly lower among the women given the magnesium sulfate. Women given magnesium sulfate were less likely to be ventilated, to develop pneumonia and to be admitted to intensive care facilities than those given the phenytoin. The babies of women who had been given magnesium sulfate before delivery were significantly less likely to be intubated at the place of delivery and to be admitted to a special care nursery than babies of mothers who had received the phenytoin. The authors conclude that there is now "compelling" evidence in favor of the use of magnesium sulfate rather than diazepam or phenytoin for the treatment of preeclampsia. Eclampsia is defined as the occurrence of 1 or more convulsions in association with the syndrome of preeclampsia. Preeclampsia is a multisystem disorder that is usually associated with raised blood pressure and proteinuria. In Europe and other developed countries eclampsia occurs in 1 in 2000 deliveries while in developing countries it varies more widely from 1 in 100 to 1 in 1700. Over half a million females die each year of pregnancy related causes and 99% of these causes occur in the developing world. Eclampsia probably accounts for 50,000 maternal deaths a year worldwide. 22604 [neu, pre] Utilizing an in vitro model and the ELISA Technique, it was found that zinc oxide at a concentration of 50 uM and 100 uM significantly inhibited the production of prostaglandin 6KF1/alpha. The study shows that the immunostimulatory effects of zinc oxide are probably related to its involvement in protein synthesis and cell division. Zinc may also show certain anti-inflammatory effects due to its ability to inhibit prostaglandin 6KF1/alpha. 21514 [der] Out of a total of 5,280 students between 11 and 15 years of age celiac disease was diagnosed in 23 cases. Most of these cases were atypical or silent forms. The prevalence of undiagnosed celiac disease was 4.36 per 1,000 screened subjects and 5.03 per 1,000 in the general population. The ratio of known to undiagnosed cases of celiac diseases was 1 to 6.4. There is a high prevalence of undiagnosed celiac disease. Frequent problems found in celiac disease patients include iron deficiency, recurrent aphthous stomatitis, failure to thrive, irritability, recurrent abdominal pain, gluten free diet during infancy, and recurrent diarrhea. This Italian study shows that celiac disease is much more common than previously thought and that most cases remain undiagnosed unless actively identified through serological screening tests. 22718 [gas] There are approximately 1.2 million chemical industrial workers throughout South Africa. In a survey of 78 workers in a chemical factory ocular disorders were more prevalent in the exposed workers (73.1%) than the nonexposed workers (43.6%). Of these ocular disorders found 40.8% were attributed to occupational exposure to chemicals. Occupational exposure to chemicals should be reduced and exposure protocols at work revised in order to reduce the prevalence of occupational related eye disorders. 22282 [env, oph, tox] This study evaluated total iron, copper, zinc and selenium and the dietary intake of these nutrients in premenopausal and postmenopausal women who mainly had stage I breast cancer and in omnivores and vegetarian controls. Plasma element levels and ratios did not distinguish breast cancer cases from controls. Only for selenium did plasma depend directly on intake. The plasma copper/diet copper ratio distinguished the premenopausal breast cancer patients from the premenopausal controls and the postmenopausal breast cancer patients from the post menopausal vegetarian controls. This study of dietary and plasma elemental levels in pre and postmenopausal women suggests significant differences in nutrition between omnivores and vegetarians, between premenopausal and postmenopausal women, and between breast cancer patients and controls. 21876 [can] It is estimated that approximately 55% of breast cancer can be explained by recognized risk factors. Risk factors include familial susceptibility, menstrual characteristics, reproductive behavior and socioeconomic status. Some recent evidence suggests that breast cancer risk can be reduced by vitamin A, carotenoids, C and E and fiber intake. Physical activity may reduce the risk to breast cancer. It was found earlier that females who were athletes during college had a reduced risk of breast cancer. Breast feeding may have some beneficial effect against breast cancer but the most protective pattern of breast feeding is unclear. There appears to be growing evidence that long term use of oral contraceptives increases the risk of early-onset breast cancer. Whether this extends to older ages is unclear. The extended or recent use of menopausal estrogens is associated with approximately 50 to 80% elevation in the risk of breast cancer. Recently attention has been drawn to environmental factors such as organochlorines, electromagnetic radiation, and electric blankets as causes though no definitive data has been found. Recently there was a possible excess of breast cancers among female electrical workers and those chronically exposed to 50-60- Hz electric fields showed increased production of estrogen and prolactin. There is a distinct north south latitudinal trend in breast cancer mortality rates; as well, a correlation with levels of solar radiation has been noted. Hypothesis: Vitamin D and/or its metabolites might reduce the risk to breast cancer. 21617 [can] Cholecystectomy rates increased 22% from 1989 to 1983. The proportion of cholecystectomy in patients with uncomplicated gallstone disease and with elective emissions declined in 1986 to 1989 but then increased rapidly after laparoscopic cholecystectomy was introduced. The age distribution and comorbidities of cholecystectomy patients did not change during the study period. Postoperative mortality rates were stable from 1986 to 1989 but decreased thereafter. The increase in cholecystectomy rates after the introduction of laparoscopic cholecystectomy occurred along with lower clinical thresholds for performing surgery. The authors found that cholecystectomy rates among elderly Medicare beneficiaries in Pennsylvania were stable in the years immediately proceeding the introduction of laparoscopic cholecystectomy in 1989 but then subsequently increased rapidly. The increased surgery rates followed the introduction of the laparoscopic procedure accompanied by lowering of the clinical threshold for performing cholecystectomy. There has been a higher aggregate of direct medical costs for cholecystectomy due to the higher surgery rate since laparoscopic procedures became available. This increase in frequency may be in part offset by the indirect cost savings to the reduced loss of time from work. Indirect cost savings if sufficiently large could lead to lower aggregate societal costs. The additional patient utility resulting from laparoscopic cholecystectomy may be significant. 22465 [gas, sur] In a rat model, severe arthritis was induced in the right knee and paw by an injection of .05 ml of a fine suspension of dead Mycobacterium tuberculosis bacilli. Eugenol at 33 mg/kg and ginger oil at 33 mg/kg given orally for 26 days resulted in a significant reduction of both paw and joint swelling. The authors note that these 2 agents may have a potent anti- inflammatory or anti-rheumatic effect. Eugenol is a popular treatment for pulpitis; it is also used as a disinfectant for dental procedures. Several reports in the past have noted the antirheumatic properties of ginger when given orally to rheumatoid arthritic patients. It is suggested that ginger's effect is due to inhibition of prostaglandin E and leukotriene formation. 21486 [rhe] In a randomized controlled trial vitamin A supplementation in 1,455 children between 6 and 59 months living in rural Northern Ghana were given 4 monthly oral doses of either 60 mg 200,000 I.U. of retinol or 30 mg for children between 6 and 11 months of age or 100,000 I.U. of retinyl palmitate plus 40 I.U. of vitamin E or placebo. The trial ran over 1 year. There was a tendency for vitamin A supplemented children but not placebo children to have elevated acute phase proteins in association with vomiting or severe diarrhea. The unsupplemented children failed to mount an acute phase response which may have contributed to their increased morbidity from gastrointestinal symptoms. 22972 [inf] This study mailed questionnaires to 200 women who were between 40 and 50 years of age and had no history of breast cancer. Each woman was asked about her risk factors for breast cancer and asked to estimate the probability of developing breast cancer and dying within 10 years, with and without screening. The mail questionnaire was completed by 73% of the women. The respondents over estimated the probability of dying from breast cancer within 10 years by more than 20-fold. The respondents over estimated the relative risk reduction by 6-fold and the absolute risk reduction by more than 100-fold. The median perceived estimate of absolute risk reduction was 6.0 breast cancer deaths per 100 women. The median calculated estimate was only .04 per 100 women. This data suggests that many women younger than 50 years of age substantially over estimate their breast cancer risk and the effectiveness of screening. Education about breast cancer risk and screening effectiveness may improve the decision making for women younger than 50 years of age and reduce their anxiety about breast cancer whether or not they choose to be screened. 22676 [can] This is a review article on the effectiveness of cholesterol- lowering diets. Two trials of dietary therapy utilizing intensive individualized counseling in persons at usual risk for coronary artery disease achieved 75 to 80% of the cholesterol lowering predicted by metabolic ward studies, and produced 5 to 14% reduction in total cholesterol levels. Four studies in high risk individuals exceeded the predictions and achieved a 4% to 17% reduction in total cholesterol levels. Six of 7 trials of diet therapy for secondary prevention had similar benefit. Four trials utilizing the population approach achieved smaller but often significant reductions in total cholesterol levels of 1 to 11%. The effectiveness of diet is enhanced when individualized counseling is utilized, follow-up is maintained and weight reduction is achieved. It is noted that the efficacy of a cholesterol-lowering diet has been clearly shown in the metabolic diet studies where dietary intake can be maximally controlled and confounding variables can be taken into account. Even though approximately 10% of the population at large and a higher percentage of patients in tertiary lipid clinics are diet resistant, dietary modification can still play an important role in lowering cholesterol levels and reducing the risk to coronary heart disease around the world. 21969 [car] The effect of 500 mg per day of methyl-B12 or placebo given intravenously once a day for 3 consecutive days given to 5 healthy, 29- to 44-year-old men was evaluated. There was no significant changes in mood or temperature NADIR between the B12 and placebo sessions. The average daytime temperature and alertness were higher during the B12 therapy than the placebo therapy. This higher alertness and temperature in the morning experienced with B12 suggests a possible direct effect of B12 on circadian oscillator. 21829 [neu, psy] There are 3 authorized claims with respect to heart disease accepted by the food and drug administration. These include dietary saturated fat and cholesterol, coronary heart disease; fruits, vegetables and grain products that contain fiber, particularly soluble fiber and the risk of heart disease and sodium and hypertension. Approval of a health claim is based on the totality of the publicly available scientific evidence and significant agreement among experts qualified by scientific training and experience to evaluate the particular relationship. On January 4, 1994 the FDA finalized requirements for health claims on dietary supplements. It is noted that the role of omega-3 fatty acids in heart disease is not authorized as well as dietary fiber by itself in heart disease is not authorized. 22347 [car] Studies have consistently observed a protective effect from oral and pharyngeal cancer with a diet high in fruit. The consumption of fruit results in a 20 to 80% reduction in oral cancer risk. Indigenous dietary practices that were found to increase the risk of oral cancer include a high intake of chili powder and wood stove cooking. Certain types of chewing tobacco also dramatically increase the risk of oral cancer. Supplementation of the diet by the use of prescribed and over-the-counter vitamins has been evaluated extensively. The findings generally point to protective influence of vitamins. One study found that vitamins A, B, C, and E, but not multivitamins, were protective. After other oral cancer risk factors were controlled for, the risk in the vitamin E users was half that of others. In another study, supplementation of vitamins A and C was protective for pharyngeal cancer, but small numbers made this study inconclusive. Vitamin E, but not multivitamins, vitamin B, or vitamin C, exerted a protective effect, after controlling for numerous confounders, in a hospital-based, case-controlled study, in four cities. Controlled chemoprevention trials utilizing retinoids and beta-carotene have shown promise. Five studies showed improvement in oral leukoplakia patients who were treated with all-trans-retinoic acid, 13-cis retinoic acid, etretinate, tocopherol, or beta-carotene. Tobacco and alcohol use definitely are related to a high proportion of oral and pharyngeal cancers in the United States. Despite methodologic difficulties in studying diet, nutrition, and oral and pharyngeal cancer, the epidemiological data shows that nutrition plays an important role in the etiology of these cancers. The most common finding is the protective effect of high fruit consumption and the carcinogenic effect of high alcohol intake. Laboratory, theoretical work, and recent clinical chemoprevention trials strongly support the epidemiological findings. 21774 [can, nut] This study measured dietary iodine intake and urinary output, as well as thyroid activity, in 12 þliving foodþ eaters (individuals who consumed uncooked lactobacilli vegan food). The living food eaters were compared to omnivores. The living food eaters were divided into two groups. There was a high urinary iodine output group which urinated greater than 900 ug/d of iodine, and a low iodine group of less than 200 ug/d. Thyroid activity was within the normal range in both groups. Dietary iodine intake was related to seaweed consumption. The highest amount of dietary iodine seen in this study may be harmful for susceptible individuals. The amount of iodine consumed by the living food eaters did not reach the RDA levels. These living food eaters need to consume seaweed or take kelp supplements to achieve the recommended daily dietary allowances. These products should be consumed with caution, since they have a very high iodine content. 21685 [nut] Over sixty-nine thousand women were evaluated from the Nurses Health Study, ages 30 to 55. With never-users of postmenopausal hormones as a reference group, it was found that ever-users had a relative risk for lupus erythematosus of 2.1, 1.2 for current users, and 1.8 for past users. A proportional increase in the risk for systemic lupus erythematosus was observed with the duration of use of postmenopausal hormones. Postmenopausal hormone therapy is associated with an increased risk for developing systemic lupus erythematosus. 22026 [aut, end] The Greek diet is high in total fat but low in saturated fat. This study evaluated 820 patients with confirmed breast cancer compared to 795 orthopedic patients and 753 hospital visitor controls for the relationship of dietary factors and risk to breast cancer. There was no significant association between total protein, total fat, categories of fat or total carbohydrates with breast cancer risk. Only total protein appeared to be positively associated with the occurrence of breast cancer with some consistency, but this was not near statistical significance. These findings do not support a role for fat or other energy-generating nutrients in the etiology of breast cancer. 21333 [can] This study evaluated adipose tissue samples from 671 men with acute myocardial infarction aged 70 years or less, and 717 men without a history of acute myocardial infarction. There was no overall difference between cases and controls with respect to the proportion of adipose tissue C18:1 trans fatty acids. The risk of acute myocardial infarction did not significantly differ with the amount of trans fatty acid intake between the highest and lowest quartiles. After adjusting for certain variables, there tended to be an increased risk of acute myocardial infarction in the upper quartiles of the C18:1 trans fatty acids, though it was not statistically significant. The authors conclude that there are definitely considerable differences between countries in dietary intakes of trans fatty acids, but these do not suggest a major overall effect of C18:1 trans fatty acids on the risk of acute myocardial infarction. The authors cannot exclude the possibility that a very high intake of trans fatty acids may have a significant impact on acute myocardial infarction. Further evaluation is needed before strong recommendations are made. 21735 [car] Over a 12 month period 46 women underwent removal of 74 silicone gel implants placed for augmentation in 26 and reconstruction in 20. Removal was from the fear of possible consequence of silicone gel in 17 patients, aesthetic concerns related to encapsulation in 14, systemic symptoms in 8, rupture determined by mammography in 7 and fear of interference with mammography or clinical examination of the breasts in 4. Ten of the 26 patients rejected replacement because of their concern about saline devices. But only 2 of the 20 reconstructed patients declined. Capsulectomy was performed in 74% of the patients. Mammography correctly predicted gel implant rupture in 7 of 8 patients. Eleven of 46 consecutive explantations were broken during removal. One of the 7 patients with severe systemic symptoms was asymptomatic postoperatively but with no changes in laboratory values. Two had 3 implants deflate at 10, 13 and 90 days as a result of manufacturing defects. Subcutaneous mastectomy patients had the least aesthetic improvement because of the prominent rippling of the anterior skin of their breasts. Two patients developed infection after capsulectomy. The authors conclude that patients who seek explantation of silicone gel implants because of fear of possible adverse effects of silicone will be pleased despite aesthetic limitations. Also the aesthetic concerns of the patients with previous augmentation exceed those of patients having reconstruction. Patients need to be carefully informed about the limitations of explantation with or without replacement. It is important that the plastic surgeon and the patient communicate regarding many of the ambiguities that are involved in the removal of the implant. The authors conclude by stating, "These patients illustrate the necessity for practicing the art of medicine, especially in the absence of the science". 21893 [sur] This study evaluated 1371 men over 40 years of age for their living habits including daily consumption of green tea and their relationship to cardiovascular disease and disorders of the liver. Increased consumption of green tea was associated with decreased serum concentrations of total cholesterol and triglycerides, and the increased proportion of HDL cholesterol. Also, there was a decrease in the proportion of low and very low LDL cholesterol which reduced the atherogenic index. Increased consumption of green tea, of more than 10 cups a day, was related to decreased concentrations of hepatological markers in the serum, aspartate aminotransferase, alanine transferase and ferritin. Green tea may be protective against cardiovascular disease and disorders of the liver. The inverse association with serum concentrations of ferritin and lipid peroxides and the consumption of green tea suggests that the tea has a protective effect on the development of cancer. 22082 [car, gas, hep] Cholecystectomy rates increased 22% from 1989 to 1983. The proportion of cholecystectomy in patients with uncomplicated gallstone disease and with elective emissions declined in 1986 to 1989 but then increased rapidly after laparoscopic cholecystectomy was introduced. The age distribution and comorbidities of cholecystectomy patients did not change during the study period. Postoperative mortality rates were stable from 1986 to 1989 but decreased thereafter. The increase in cholecystectomy rates after the introduction of laparoscopic cholecystectomy occurred along with lower clinical thresholds for performing surgery. The authors found that cholecystectomy rates among elderly Medicare beneficiaries in Pennsylvania were stable in the years immediately proceeding the introduction of laparoscopic cholecystectomy in 1989 but then subsequently increased rapidly. The increased surgery rates followed the introduction of the laparoscopic procedure accompanied by lowering of the clinical threshold for performing cholecystectomy. There has been a higher aggregate of direct medical costs for cholecystectomy due to the higher surgery rate since laparoscopic procedures became available. This increase in frequency may be in part offset by the indirect cost savings to the reduced loss of time from work. Indirect cost savings if sufficiently large could lead to lower aggregate societal costs. The additional patient utility resulting from laparoscopic cholecystectomy may be significant. 22465 [gas, sur] Fifteen patients between 23 and 66 years of age suffering from different types of cancer including breast, testicular, lung, cavum cancer, myosarcoma and uterine sarcoma, received chemotherapy including adriamycin at 30-60 mg/m2. They were evaluated for lipid peroxidation products and antioxidant systems as well as vitamins and trace elements. Only plasma zinc and selenium were significantly decreased in cancer patients compared to controls. Plasma copper and vitamin A levels remained unchanged. Lipid peroxidation products were not significantly increased in cancer patients compared to controls. Adriamycin administration, along with other cancer drugs, resulted in a significant increase in thiobarbituric acid reactive substances, but not in organic hydroperoxides. Plasma vitamin E decreased significantly whereas the other nutrients remained unchanged after adriamycin administration with other anticancer agents. Adriamycin administration is associated with dose related cardiomyopathy; this increases the risk of heart failure. It is believed that adriamycin induces lipid peroxides and oxidative byproducts that damage the heart. In this study the antioxidants blood glutathione, plasma glutathione peroxidase, selenium and zinc were decreased in cancer patients whereas vitamin E; beta- carotene increased; copper and vitamin A remained unchanged. This study showed that cancer leads to a decrease in selenium and zinc status. Also, with chemotherapy, there is an increase in thiobarbituric acid reactive substance metabolites and a decrease in vitamin E. This study confirms that free radical mechanisms might be involved in the toxicity from anticancer drugs. 22028 [can] This study evaluated 67 patients with alcoholic cirrhosis 33 of whom received vitamin E at 500 mg a day and 34 who received placebos over a 1 year period. Vitamin E levels were significantly lower in patients with more severe liver disease. Vitamin E supplementation significantly increased serum vitamin E levels. Alcohol ingestion and hospitalization were similar in both groups. There was no significant difference in mortality between the 2 groups. The vitamin E supplementation with 500 mg of alpha-tocopheryl acetate formulation during 1 year did not influence liver function parameters, mortality or hospitalization rates of decompensated alcoholics even though vitamin E levels were significantly increased. The lack of vitamin E supplementation benefit suggests that in advanced cirrhosis liver function in these patients cannot be improved. Evidence supporting lipid peroxidation and altered antioxidant mechanisms in response to heavy alcohol consumption appear solid. In order to protect from the hepatic consequences of free radicals intervention needs to be attempted at earlier stages of the disease. 22119 [gas, hep] This letter to the editor comments on a commentary in the August 1994 issue of the American Journal of Clinical Nutrition which suggests that antioxidant supplementation may have pro-oxidant or toxic effects. The authors recognize that the antioxidant supplement debate will be a focus of controversy for many more years. There is no question that a large body of evidence suggests that antioxidants may be of benefit in both the prevention of cardiovascular disease and cancer. It is also noted that some research has shown no benefit and a few reports suggest detrimental effects on antioxidants. The authors encourage objective and healthy debate versus polarizing types of commentary. Conjecture is not what is needed. With regards to the amount of vitamin E and beta-carotene in the Finnish study, it is not known how the effect of 36 years of smoking at 20 cigarettes per day will be affected by antioxidant supplements. 22738 [can, car] This study evaluated endothelial nitric oxide synthase in the lungs of 22 patients with plexogenic pulmonary arteriopathy, 24 patients with secondary pulmonary hypertension and 23 control subjects. Pulmonary hypertension was found to be associated with a reduced expression of endothelial nitric oxide synthase. It is possible that the decreased expression of nitric oxide synthase contributes to the pulmonary vasoconstriction and to the excessive growth of the tunica media that is seen in the disease. L-arginine can stimulate nitric oxide production and has been shown to reduce pulmonary pressure in patients with pulmonary hypertension in the past. 22909 [car, pul] This study evaluated healthy, postmenopausal women who were at least 2 years from the last menstrual cycle. Twenty-eight women were using estrogens and 43 were nonusers. In the estrogen users most were taking conjugated estrogen and approximately 1/2 were receiving a progestin. The estrogen users had better immediate and delayed verbal memory scores than the nonusers. The improvement in verbal memory in the estrogen users was not affected by progestin use. Estrogen use in healthy postmenopausal women is associated with better performance on specific memory tests. Other cognitive function was not affected by the estrogen. 21548 [end, gyn, neu] This study evaluated nicotinamide in a human model for its ability to prevent insulin-dependent diabetes mellitus. The authors found that standard nicotinamide given at low doses of 2.5 mg/kg per body weight and Enduramide at 6.7 mg/kg of body weight showed no significant differences in kinetics. A dose of Enduramide at 2 gm resulted in greater bioavailability than the long-acting formulation tested. Metabolic clearance pathways of nicotinamide are saturated at the doses currently used in human trials. Eight adult men with an average age of 20 years and an average body weight of 75 kg were evaluated in this study. Insulin-dependent diabetes mellitus has a prediabetic phase in which there is possibility of medications being administered that can halt the autoimmune destruction of the beta cells. Nicotinamide is a derivative of niacin. It is a weak free-radical scavenger and inhibits interleukin-1B-induced nitric oxide synthase and poly(ADP- ribose) synthetase in islets. Poly(ADP-ribose) synthetase is an intracellular enzyme that repairs DNA strand breaks utilizing NAD as an energy source at the expense of other cell functions. Nicotinamide can prevent alloxan induced DNA strand-breaks which has diabetogenic actions. Nicotinamide at 500 mg/kg body weight also prevents the onset of insulin-dependent diabetes mellitus in spontaneously diabetic mice. Studies in humans with newly onset diabetes have shown only marginal and inconsistent improvements in glucose tolerance with nicotinamide. Nicotinamide is believed to be essentially nontoxic. Its use has been largely restricted to adults. It has been given to humans in a long-acting preparation in a dose of 1 to 3 gm per day, which is equivalent to 15 to 45 mg/kg, some 10 to 33 times less than the dose observed to prevent insulin-dependent diabetes mellitus in animal models. More needs to be learned about this medication at high dose . . . not only in adults, but in children as well. 21752 [end] This study evaluated 13 individuals between 50 and 84 years of age who had borderline hypercholesterolemia with a range greater than 5.17 mmol/L. Subjects had been participating in a supervised aerobic exercise program for at least 3 months before the study began; all were in good health. The subjects consumed 100 gm of oat bran from the Quaker Oats Company per day for 4 weeks. The subjects received recipes for oat bran cereal and baked products and instructions on substituting these products for starch based products in the normal diet. The mean daily oat bran consumption was in the 94 gm per day range. The mean total and LDL cholesterol levels were reduced significantly. Plasma lipoprotein (a), triglycerides and HDL cholesterol were not changed in this study. These results confirm that oat bran can lower total and LDL cholesterol. Lipoprotein (a), though not affected by oat bran, has been lowered by niacin, weight loss, palm oil and fish oil. 21482 [car, nut] A meta-analysis of a variety of studies shows a relationship between particulate air pollution and exacerbations of illness in people with respiratory disease. The increase in urban air pollution may be related to the observation of increased cardiovascular deaths. The authors hypothesize that acidic ultra- fine particles that are derived from air pollution can provoke alveolar inflammation, causing changes in blood coagulability and releasing the mediators that can trigger acute respiratory illness in susceptible individuals. 21659 [pul] Evidence has shown that even low blood levels of lead may cause harm to the developing nervous system of children. In the U.S.A., the blood lead value that should be a concern was established in 1991 as 10 ug/dl. U.S. public health officials endorse universal lead testing in children under the age of 6 unless the local prevalence of raised concentrations is known to be low as a result of extensive testing. This recommendation has not been successful in many parts of the United States. Health care providers believe that lead is a hazard mainly in deteriorating inner cities of the U.S. north east. Providers in Oregon and other western states believe that lead is not an issue and are reluctant to conduct widespread testing. The rejection of universal lead screening raises the question of what will take its place. The data in Oregon suggests that each year at least 1200 children with potentially harmful blood lead concentrations would go undetected if screening were abandoned. One way to identify children at risk is to ask parents during a child's routine medical visit. This approach has its flaws. If targeted screening is to succeed health care providers and public health officials must work together. There has been a sharp decline in elevated blood lead levels over the last 2 decades mainly due to the elimination of lead from gasoline, food cans, plumbing and paint. Targeted screening programs are important for children who have been exposed despite these preventive efforts. 21471 [env, ped, tox] Numerous studies have noted that oxygen free radicals are involved in the development of tissue damage in acute pancreatitis. Oxygen radicals are generated in the early phase of the disease before tissue damage is detectible by histology. The mechanism which leads to oxidative stress is not fully understood. Scavenger treatment early in experimental acute pancreatitis has shown benefit. Antioxidant treatments with selenium in clinical trials have shown benefit in reducing the lipid peroxidation and improving antioxidant status. Larger trials are needed. 22490 [gas] This study evaluated 58 patients needing hemodynamic monitoring due to septic shock. These patients were evaluated 72 hours after the onset of sepsis. They received either 150 mg/kg of intravenous N- acetylcysteine or a placebo over a 15 minute period, then a continuous infusion of 12.5 mg/hour of N-acetylcysteine or a placebo over approximately 90 minutes. Forty-five percent of the patients responded to the N-acetylcysteine infusion. The N- acetylcysteine responders also showed an increase in gastric intramucosal pH, a decrease in veno-atrial Pco2 and an increase in oxygen delivery, cardiac index, stroke index, and left ventricular stroke work index, as well as a significant decrease in systemic vascular resistance in comparison to baseline. N-acetylcysteine nonresponders and the placebo group had no significant changes in any of these variables. The N-acetylcysteine responders had a 69% survival rate compared to 19% of nonresponders. N-acetylcysteine provided a transient improvement in tissue oxygenation in about half of the septic shock patients, as indicated by an increased V02 and gastric intramucosal pH and a decrease in veno-arterial C02. The fact that there is a varying response to N-acetylcysteine suggests that in some patients sepsis irreversibly damages the microvasculature to the extent that N-acetylcysteine has no effect. Further investigation is needed to determine whether N- acetylcysteine can be effective in the treatment of sepsis or whether the N-acetylcysteine challenge was merely diagnostic. 21654 [cri] diet. 22551 [can, car, nut] This was a randomized, controlled, cross-over study in 14 smoking men with elevated ferritin concentrations. These subjects were heavy smokers and had previously experienced blood letting. During the intervention periods the individuals donated 450 mg (500 ml) of blood 3 times in 14 weeks. Serum ferritin concentrations were reduced by 44% during the venesection periods. The maximal oxidation velocity was decreased by 20% and the lag time to the start of oxidation was lengthened by 33%. These results show that reduction of body iron stores by venesection can increase oxidation resistance of serum VLDL and LDL cholesterols in regularly smoking men. It was noted that plasma vitamin C concentrations tended to increase and the concentrations of oxidized forms of ascorbic acid, dehydroascorbate, tended to decrease during the venesection periods. Changes in plasma vitamin C and oxidized vitamin C correlated with the changes in oxidation resistance of VLDL/LDL. This suggests that iron depletion may have increased the oxidation resistance of lipoproteins in part through the elevation of plasma concentrations of the antioxidatively active form of vitamin C which is the reduced ascorbic acid. Plasma vitamin E concentrations tended to decrease during the blood letting period and to increase during the control period. Mean plasma levels of vitamin E were very low in these heavily smoking individuals. The present study gives indirect support for the role of iron overload in the etiology of coronary heart disease due to the fact that depleting iron results in an increased resistance to lipid oxidation. If the antioxidative effect of donating blood is confirmed than venesection may be a safe and inexpensive therapy which could be used in the prevention and treatment of free radical initiated diseases, especially in persons with high iron stores. 21839 [car] Fifty-eight early postmenopausal women attending metabolic bone disease outpatient clinics were randomly allocated into 4 treatment groups and monitored for up to 4 years. All of the patients received 1 gm per day of elemental calcium. One group received percutaneous administration of hormone replacement therapy and another group received intermittent cyclical etidronate. Another group received both of those therapies and the last group received calcium alone. The combined therapies resulted in an increase in bone mineral density of the vertebra of 10.9% and in the femora of 7.25% at 4 years. For the patients treated with the intermittent cyclical etidronate, the increase was 6.79% and 1.2%, while hormone replacement therapy was 6.78% and 4.01% increase in bone mineral density in the vertebra and femora, respectively. The group treated with calcium alone lost 3.81% and 4.96% of the bone mineral density in the vertebra and femora. Patients who received no specific treatment lost 8.58% from the vertebra and 7.83% from the femora over 4 years. This study shows those treated in early menopause had an additive effect of intermittent cyclical etidronate and hormone replacement therapy on bone mineral density in both the hip and vertebra. The combined therapy prevented the occurrence of osteomalacia associated with etidronate. 22846 [ort, end] Male guinea pigs were given low, medium and high vitamin C concentrated diets. Heart vitamin C was strongly dependent on dietary vitamin C; heart vitamin E showed a trend to increase as a function of vitamin C level in the diet. The low vitamin C diet decreased body weight gain, food intake and heart malondialdehyde without changing lipid peroxidation; whereas the high vitamin C intake increased oxidized glutathione and glutathione peroxidase and decreased body growth. A tendency to show higher levels of all the first line antioxidants (reduced glutathione, uric acid, superoxide dismutase, catalase and glutathione peroxidase) at either extreme high or low dietary levels of vitamin C was observed. The guinea pig heart showed capacity for enzymatic but not for nonenzymatic in vitro lipid peroxidation. The authors conclude that dietary vitamin C is able to increase the global antioxidant capacity of the heart tissue. 22005 [car] This study evaluated 65 pregnant females of whom 27 were enrolled in exercise classes according to Canadian guidelines. Thirty-eight were sedentary controls. No effect of exercise on posture was detected. The results showed that fitness classes for pregnant women designed according to the Canadian guidelines had no detectible benefit on posture during pregnancy. There was some increased curvature of the lumbar spine during pregnancy and lordosis at 4 months postpartum that was still higher than mid pregnancy values. Curvature of the thoracic spine varied little. The factors effecting postpartum changes in posture remain undiscovered. 22298 [obs, ost] Cryoglobulinemia is a pathologic condition characterized by circulating immunoglobulins that precipitate reversibly in the cold. This occurs in approximately 6% of patients with lymphoproliferative, infectious or autoimmune disorders. If no underlying cause is found this syndrome is called essential cryoglobulinemia. In this 8 week double-blind randomized trial of 10 patients with mixed cryoglobulinemia, eicosapentaenoic acid was given at 3 gm per day and docosahexaenoic acid at 2 gm, while another 10 mixed cryoglobulinemia patients received an olive oil placebo. No significant differences were found in clinical symptoms between the 2 groups, however the percentage of patients who reported clinical improvement were higher in the fish oil group. When following serologic parameters there was no change in the placebo group while in the fish oil group there was a significant decrease in cryocrit and rheumatic factor levels. These authors could not show an improvement in clinical symptoms in patients with mixed cryoglobulinemia with fish oil supplementation. This study did show some improvement in serologic parameters possibly involved in the pathogenesis of the disorder. Newer therapeutic trials with higher doses of fish oil and/or for longer periods of time may be warranted in patients with mixed cryoglobulinemia. 21547 [hem, rhe] This is an extensive review article on the role of recycling drinking water from secondary waste water. Based on the studies, the authors concluded that properly treated secondary waste water can be recycled into safe drinking water for public consumption. 21505 [env, tox] This study evaluated 22 females and 7 males with moderate to severe depression with 3 day food records. Females as a group consumed a diet that provided 100% of the RDAs where the diet of the males was deficient in energy and 4 of 16 nutrients. Nutrients in the males which did not meet the RDAs included energy, vitamin B6, calcium, selenium and zinc. Vitamin B1 and riboflavin (vitamin B2) as well as vitamin A barely made the RDAs. 22180 [nut, psy] High intensity strength training may reduce a postmenopausal woman's risk for osteoporotic fracture. Such training is protective on bone mineral density and promotes increased muscle mass, strength, dynamic balance and overall activity levels in postmenopausal women. This is the first time that a single program has shown to affect so many different risk factors for osteoporosis. In this study women trained on pneumatic machines. However, a home-based strength training program, using inexpensive dumbbells or water filled milk containers, may also give benefit. The strengthening program is feasible for frail individuals; it may significantly improve strength, mobility and functional status without risk to subjects. In this study, 39 white, sedentary, postmenopausal women were randomized to an exercise training group and a control group. Women in the exercise group participated in high intensity strength training 2 days per week for a year. Pneumatic resistance machines were used; exercises included hip extensions, knee extensions, lateral pull-downs, back extensions and abdominal flexion. At the end of the study femoral neck bone mineral density and lumbar spine density in the strength-trained women had increased 1.0%. In the controls femoral neck bone mineral decreased by 2.5% and lumbar spine bone mineral density decreased by 1.8%. The total body mineral content was preserved in the strength trained women, but a decrease of 1.2% was seen among women in the control group. Total body muscle mass, muscle strength and dynamic balance increased in the strength trained women and decreased in the controls. Women who exercised increased their energy expenditure and activities exclusive of the intervention by 27%. Controls decreased their spontaneous activity by 25%. 21897 [ort] This study evaluated 24-hour energy expenditures, resting and nonresting energy expenditure and thermic effect of feeding in 18 obese subjects and 23 subjects who had never been obese. The subjects were evaluated at their usual body weight and after losing 10 to 20% of their body weight by underfeeding, or after gaining 10% by over feeding. The maintenance of body weight at a level 10% or more below the initial weight was associated with a mean reduction in total energy expenditure of 6 kcal per kg of fat-free mass per day in subjects who had never been obese and 8 kcal per kg per day in obese subjects. The maintenance of body weight at a level 10% above the usual weight was associated with an increase in total energy expenditure of 9 kcal per kg of fat-free mass per day in subjects who had never been obese and 8 kcal per kg per day in obese subjects. The thermic effect of feeding and nonresting energy expenditure increased by approximately 1 to 2 and 8 to 9 kcal per kg of fat-free mass per day respectively after weight gain. The authors conclude that maintenance of a reduced or elevated body weight is associated with a compensatory change in energy expenditure which opposes the maintenance of the body weight that is different from the usual weight. These changes may account for the poor, long term outcome of treatments for obesity. Many obese individuals who lose weight have metabolic alterations similar to those seen in the test subjects. The reduction of energy to a level of 15% below that predicted for body composition as a result of a 10% decrease in body weight is large, especially when one considers that the average daily intake of 2500 kcal would be associated with a positive energy balance of approximately 375 kcal per day. The sense of hunger or dysphoria that is associated with a state of reduced energy expenditure will promote Uincreased food intake and further widen the difference between the energy output and intake. Physicians need to know that for certain obese patients the achievement of a more healthful body weight may be accompanied by metabolic changes that make it difficult to maintain the lower body weight. 21934 [end, obe] From a total of 789 histologic sections over an 8 year period, 51 cases of allergic fungal sinusitis were identified in patients showing allergic mucin. Thirty-one were diagnosed as having allergic fungal sinusitis utilizing rigid criteria. Twenty cases were classified as allergic fungal sinusitis-like syndrome. The prevalence of strictly defined allergic fungal sinusitis was 4%. Dematiaceous fungi were the predominant species cultured. All the patients had polyps, 54% had asthma, 27% had aspirin sensitivity, 65% had eosinophilia, and 69% had increased total IgE levels. The authors note that allergic fungal sinusitis is not a rare condition. Because of its position it is not a benign condition. Failure to recognize allergic fungal sinusitis can result in complications such as blindness and intracranial abscess. Allergic fungal sinusitis-like syndrome is a new term that describes patients who have clinical and histopathologic features of AFS but fail to demonstrate fungi in the histopathologic sections or cultures of sinus tissue. Treatments include the use of saline/hydrogen peroxide and antifungal nasal washes, inhaled steroids or disodium cromoglycate or oral prednisone and antihistamines, antifungals and avoidance of the antigen. 21871 [all, oto] This study evaluated the effect of Vitamin E supplementation on 30 top-class cyclists for a period of 5 months. The supplemented group took Vitamin E at 110 mg of alpha-tocopherol-acetate 3 times a day for a total of 330 mg per day. Vitamin E levels rose in the supplemented group whereas they tended to decrease in the placebo group. Physical performance did not improve in the vitamin E supplemented group compared to the placebo group. Heart rates did not change significantly. Lactate concentrations at aerobic threshold and anaerobic threshold were similar. There was a significant reduction in creatine kinase in the serum of the vitamin E supplemented group. There was a trend towards a decreased GOT, GPT and LDH in the vitamin E group. There was a significant reduction in malondialdehyde serum levels measured in the vitamin E supplemented group. These results suggest a protective effect of vitamin E supplementation against oxidative stress which is caused by strenuous exercise. 21388 [car, exe] This study evaluated 75 white adults between 19 and 25 years of age who were either in a control group or received 1,000 mg of calcium carbonate (two 500 mg Os-Cal tablets) or received 24 fluid ounces of milk either skimmed, 2%, or whole, per day while continuing their usual dietary practices. All systolic blood pressures, regardless of the treatment group, declined over a 6 week period. Diastolic pressures decreased only in the 2 calcium supplemented groups. Serum ionic calcium levels increased from the dietary calcium-supplemented group from 1.08 to 1.15 mmoles/L but not for the calcium carbonate-supplemented group. Dietary intake for calcium in all groups were below the recommended dietary allowance. When the total calcium intakes through diet and supplements were evaluated the treatment group intakes were above the RDA for this age group. Calcium supplementation produced a significant lowering of diastolic blood pressure in this study in normotensive young adults. Dietary supplementation also increased serum ionic calcium. 22653 [car] Magnesium has been used for more than 60 years for the prophylaxis against eclamptic seizures. It became standard treatment over the next 30 years and was associated with a dramatic reduction of maternal and neonatal morbidity related to eclampsia. Whether magnesium was responsible for this outcome, it was never tested in a randomized trial. This approach was criticized because there were better anticonvulsants but magnesium was safe for fetuses at therapeutic effective levels. New data suggests that magnesium is effective as both therapy for and prophylaxis against eclampsia and its not only safe for the neonate but potentially beneficial. Magnesium is far better than Phenytoin in preventing eclamptic seizures. 22917 [gyn, obs] This review article reviews the role of polyunsaturated fatty acids of the omega-6 and omega-3 families and their effect on blood pressure. Most intervention studies show that changing from a high fat, low-linoleic-acid diet to a low-fat, high-linoleic- acid diet lowers blood pressure. Independent studies have not confirmed the linoleic-acid hypothesis. Omega-3 fatty acids have been shown to lower blood pressure only in pharmacologic dosages that generally are not taken by the public. It is believed that the omega-6 and omega-3 fatty acid families work by altering prostaglandin metabolism. 21564 [car] This is a review of a hypothesis which suggests that the essential fatty acids, linoleic acid and gamma-linolenic acid play important roles in cancer treatment. Oxidation of linoleic acid by lipoxidase especially increases tumor cell death while gamma-linolenic acid inhibits urokinase-type plasminogen activator activity. Increased urokinase-type plasminogen activator activity is responsible for cancer invasion and metastasis primarily and secondarily responsible for proteolysis lipoxidase. The authors feel the addition of linoleic acid and gamma-linolenic acid to therapeutic regimens may be beneficial in cancer treatment. 22387 [can] This is an extensive review article on the role of fibrinogen and cardiovascular disease. Fibrinogen is involved in blood coagulation and is an important determinant of blood viscosity and blood flow. Elevated plasma fibrinogen levels have been epidemiologically shown to increase the risk for cardiovascular disorders. These include ischemic heart disease, stroke and other thromboembolic events. Increased plasma fibrinogen may promote a prothrombotic or hypercoagulable state, and may, in part, explain the risk of stroke and thromboembolism in conditions such as atrial fibrillation and cardiac dysfunction. Human fibrinogen is a large glycoprotein (340,000 Da) composed of 3 pairs of nonidentical polypeptide chains (A alpha, B beta and gamma) joined together by disulphide bonds. Fibrinogen is an important determinant of both rheological characteristics of blood flow and of platelet aggregability. Fibrinogen is an essential component of the blood coagulation system, being the precursor of fibrin. Usual plasma levels are between 1.5 and 4.5 g/l, a concentration far greater than the minimum concentration needed of 0.5 to 1 g/l for haemostasis. In 9 out of 10 studies, plasma fibrinogen levels correlated significantly with the degree of coronary artery disease. A positive correlation between plasma fibrinogen and fibrin D-dimer has been seen in patients with atrial fibrillation. Intermediate levels of plasma fibrinogen have also been found in patients with paroxysmal atrial fibrillation. Psychological and mental stress can increase plasma fibrinogen levels. Fibrinogen levels are significantly associated with cerebrovascular disease. Plasma fibrinogen concentrations have been shown to be an important independent predictor of coronary death in patients with intermittent claudication. In patients with systemic hypertension, fibrinogen concentrations and plasma viscosity are independent predictors of blood pressure. In diabetic patients, a significant positive correlation has been found between plasma fibrinogen and fasting glucose levels, serum cholesterol levels, glycosylated hemoglobin and urinary albumin excretion rates. In individuals who use oral contraceptives, an increased risk of thrombotic events measured by elevated platelet aggregation and plasma fibrinogen levels has been discovered. There appears to be a hormonal influence on fibrinogen levels. Smoking has a dose-effect relationship on plasma fibrinogen levels. In obese patients with a body mass index of more than 30, plasma viscosity and fibrinogen levels are significantly increased. Strenuous exercise is associated with lower fibrinogen and cholesterol concentrations. Increased alcohol consumption may have a small but significant effect on decreasing plasma fibrinogen levels. The role of social class and psychosocial factors in determining plasma fibrinogen levels is controversial. Plasma fibrinogen levels are increased in patients with hyperlipidaemia. Dental disease is associated with myocardial infarction, and increased fibrinogen and white blood cell counts may partly explain this. The genetic influence on plasma fibrinogen formation, and genetic heritability, may account for 51% of the variance of plasma fibrinogen levels. There is a wide range of reference values for plasma fibrinogen with a mean "normal" value between 2.3 and 3.1 g/l in different population studies. Elevated plasma fibrinogen levels are consistently associated with various cardiovascular disorders. Because the process of atherogenesis has similarities to inflammatory diseases, the elevation of plasma fibrinogen levels may reflect the severity of the vascular disorder as a secondary phenomenon rather than act as a true prognostic factor. The strong hereditary determination of fibrinogen makes it less likely that raised fibrinogen levels are simply a secondary response to cardiovascular disorders. Raised plasma fibrinogen levels are known to precede in cardiovascular disorders. Raised plasma fibrinogen levels are likely to reflect a pre-existing prothrombotic, or hypercoagulable, state. Acts to lower fibrinogen levels include ceasing smoking and increasing exercise. Drugs that may lower fibrinogen include ticlopidine, stanzolol, oxypentifylline, calcium dobesilate, propanolol, nislodipine and the fibrates. These drugs have other pharmacologic effects other than lowering fibrinogen concentrations and are not practical therapeutic options. There is controversy with regards to diet lowering plasma fibrinogen levels. Fish oil supplementation may result in the reduction in plasma fibrinogen levels. Moderate alcohol consumption, increased garlic, regular exercise, weight loss and better diabetic control are also favorable to lowering fibrinogen levels. 22044 [car] Colchicine's main pharmacologic property is the ability to block mitosis in metaphase because the mitotic spindle fails to form. Cells with the highest rate of division are earlier effected thus preventing the destructive effect of infiltrating neutrophils. Colchicine also prevents the release of histamine-containing granules from mast cells and also the processes involved in the translocation of granules by the microtubular system. The inhibition of tubulin polymerization induced by colchicine prevents intracellular events linked to the function of cytoskeleton including the spread of signals from surface cell receptors to the cytoskeleton, transportation and translocation to the cell membrane and the secretion of molecules via the tubulin system. A direct consequence of this cytoskeleton disruption is the change of cell shape observed also in the glomerular epithelial cells by electron microscopy. Colchicine has been shown to prevent renal allograft rejection by inhibiting adhesion molecules function on epithelial surface. Cultured endothelial cells pre-exposed to colchicine and then challenged with interleukin 1B show a down-regulation of cell surface expression of intracellular adhesion molecule-1 and endothelial leukocyte adhesion molecule. The authors theorize that colchicine in some way inhibit the development of acute experimental glomerulonephritis induced by mesangial trapping of IgA lectin aggregates. This may be due to the inhibition of binding of these complexes to mesangial IgA and lectin receptors which are likely to be disturbed by tubulin depolymerization induced by Colchicine. Colchicine might inhibit integrin expression on mesangial cells with modifications in renal hemodynamics and mesangial channels macromolecular flux, inhibiting the trapping of IgA/lectin complexes and the mesangial cell responses with subsequent nephritogenic process. This rat study showed that pretreatment for 4 days with colchicine by mouth inhibited the development of IgA mesangial deposits. The protective effect of colchicine may be due to the inhibition of binding of the aggregates to IgA and lectin receptors expressed at the surface of the mesangial cells. Another effect might be mediated by the inhibition of integrin expression on the mesangial cells. It may also be that the protective effect of colchicine on the development of experimental IgA nephropathy might be mediated by an inhibitory effect on mesangial cell surface integrins expression, with subsequent modification of the binding cell matrix and the focal contacts between mesangial cells and GMB, which maintain the structure and function of the glomerular tuft. The modifications in renal hemodynamics and mesangial channel macromolecular flux might inhibit the trapping of IgA/lectin complexes, the mesangial cell response and the subsequent nephritogenic process. 22637 [imm, nep] Sixty-four patients were diagnosed with severe preeclampsia. One group of 34 patients received magnesium sulfate at a 4 gm intravenous loading dose over 10 minutes followed immediately by an intravenous infusion of 1 gm per hour as maintaining dose until 1 day after delivery. Both the placebo and the magnesium treated group were given bed rest, a low salt (3 gm) and high protein diet and antihypertensive medication. There was no occurrence of eclampsia in either group. There was no statistical significance in the final delivery method. The magnesium treated group had a higher cesarean section rate which is most significant due to fetal distress. Group 1 had significantly more babies with poor apgar scores than group 2. During the treatment period for those with a gestational age of less than 34 weeks, there were 2 patients with abruptio placenta in the magnesium treated group but none in the placebo group. According to this study, magnesium sulfates minimal efficiency, and adverse side effects, also make magnesium a poor choice in the management of preeclampsia. The authors recommend management of preeclampsia without magnesium sulfate. 22075 [gyn] This study evaluated diet and bone mineral density in 139 premenopausal women, 30-39 years of age, in New York between September 1988 and August 1992. A food frequency questionnaire was used to determine nutrient intake for both the year prior to the year of bone density measurement and for the ages 13 to 17. There was no relation between lumbar spine or distal forearm bone density in any nutrient studied for either the current or the teenage diet. Current dietary calcium intake was modestly related to hip bone density. When fiber intake was added, the association between calcium and hip bone density was strengthened. This is to be expected since fiber affects calcium absorption. In the teenage diet phosphorous and calcium intake were related to hip bone density. A higher lifetime calcium intake was associated with a higher hip bone density compared with a low lifetime calcium intake. An increase in teenage calcium intake from 800 to 1,200 mg per day is estimated to increase hip bone density by 6%. If maintained, the potential increase in bone mass may offer protection against hip fractures. 21849 [nut, ort] Hypericin is a polycyclic, aromatic, naphthodianthrone. Several of its structural analogs are virucidal agents that effectively inactivate retroviral particles including the human immunodeficiency virus type I in vivo and in vitro. Hypericin binds to cell membranes and cross links virus capsid proteins. This action results in the loss of infectivity and ability to retrieve the reverse transcriptase enzymatic activity from the virion. This study evaluated its additive potential to inactivate infective viruses and blood components intended for transfusion. Complete inactivation of 106 tissue culture-infective doses of human immunodeficiency virus was obtained in whole blood and in diluted red packed cells after illumination with fluorescent light for 1 hour. Loss of viral infectivity to cultured CEM cells has been monitored by use of a detection assay for human immunodeficiency virus p55 in enzyme-linked immunosorbent assay and cytopathic assays. In physiologic media hypericin interacts with albumin and lipoproteins retaining the virucidal activity in bound form. This molecule is negatively charged and forms organic inorganic monobasic salts in physiologic pH. There is ion pairs different in their virucidal activity. Hypericin may be useful for inactivation of infectious virus in red cells due to its transfusibility, virucidal activity, the wide range of viruses affected and the absence of effects on stored red cells. 22443 [inf] This discussion suggests that the increased risk associated with abdominal obesity is mediated by increased levels and fluxes of free fatty acids. The article reviews strategies for reducing free fatty acid levels and or flux which include the very low fat, low glycemic index diet which promotes insulin sensitivity via exercise, chromium supplementation, soluble fiber or drugs, antilipolytic agents, the stimulation of hepatic lipid oxidation with hydroxycitrate, carnitine and possibly omega-3 fatty acids. The authors note that when the treatment of obesity appears to be refractory it may be possible to reduce the cardiovascular risk associated with obesity by modulating free fatty acids. 22905 [car, met, obs] This article reviews the nutritional requirements when the body is faced with environmental and physical stress. Metabolic adaptations to heat, cold and high altitude exposure can result in alterations in nutrient requirements. Energy expenditure is increased in all 3 of the above categories. B vitamin cofactor requirements increase in proportion to energy expenditure due to oxidation of fat and carbohydrate. Increased B vitamin nutrient requirements are usually met by an increasing dietary intake to meet energy needs. Nutrients such as iron may be required in greater amounts to meet the altitude-induced hematopoietic response in females. Additional quantities of vitamins and minerals with antioxidant properties may be beneficial to reduce the increased oxidative stress that is associated with heat, cold or high altitude environments. Women and men working in severe environments may benefit from supplemental antioxidant nutrients, such as vitamins E, C, beta- carotene, selenium, copper, zinc and manganese, to reduce lipid peroxidation and protein and DNA damage. Reflected sunlight from ice, snow or sand, cloudless skies of the desert and high elevations and the rarefied air of high altitude can contribute to the solar load and associated photobiologic effects. These effects, in combination with enhanced aerobic metabolism from increased energy expenditure, result in increased potential for generating reactive oxygen species which may result in the damage of lipid components of membranes, enzyme proteins and DNA. Supplemental antioxidants and/or foods rich in antioxidant nutrients may be valuable during periods of prolonged work and recreation in extreme outdoor environments. 21946 [env, exe, nut] Allergic colitis is characterized by inflammatory changes in the rectum and colon as a result of immune reactions to ingested food proteins. This condition predominantly affects infants who, in the first months of life, have rectal bleeding and they generally recover promptly after elimination of the allergen from their diet. The antigens usually come from formulas or may be found in human milk as a result of the maternal diet. Cow's milk allergy is one etiologic factor. Other foods include wheat, eggs, corn, fish, seafood, and nuts. By far the most common antigens in allergic colitis in infants are cow's milk and soy formulas. 22967 [gas, ped] Samples of palladum were obtained at necropsy from 9 cirrhotic patients who died in a hepatic coma. The samples were compared to 12 age-matched control subjects free from hepatic, neurological, or psychiatric disorders. It was found that the mean pallidal manganese concentration was 3-fold higher in the cirrhotic patients per ug/g dry weight compared with controls. Histologic examination revealed Alzheimer type 2 astrocytosis in all cases of hepatic coma but did not demonstrate melanin deposition, hemorrhage, calcification or neurofibromatosis. This data of increased concentrations of manganese in the pallidum of cirrhotic patients offers a plausible explanation for the pallidal signal hyperintensity on T1-weighted MR images observed in these patients. Chronic manganese toxicity results in extrapyramidal symptoms related to alterations of dopamine function, which has been previously described in cirrhotic patients. Extrapyramidal symptoms described in cirrhotic patients could be a result of dopaminergic dysfunction due to increased pallidal manganese concentrations. 22011 [gas, hep] Depression and psychosocial features are risk factors for coronary artery disease. Evidence is increasing that psychosocial treatment such as support groups, behavior therapy and stress management can improve survival in patients following a heart attack by as much as 25% which is comparable to the effect of beta-blockers. The appreciation for the role of psychosocial factors in coronary artery disease has only been apparent the last 3 to 5 years due to definitive epidemiologic data. In a recent study of 222 men and women hospitalized for acute myocardial infarction at the Montreal Heart Institute in 1991 and 1992 depression was found to be an important predictor of death during the first 18 months of follow- up. Those who had a mild or moderate depression as measured by the Beck Depression Inventory had a risk-adjusted 6.5-fold higher likelihood of death compared to MI patients who were not depressed. In depressed patients the risk of death was increased if they had premature ventricular contractions or a left ventricular ejection fraction of less than 35%. Drug therapy or psychotherapy may be of benefit to these patients. In a Mayo Clinic study, 380 patients with coronary artery disease were undergoing cardiac rehabilitation. Those who had psychological stress upon entry into the program had a 3.5-fold increase in the risk of a subsequent cardiac event in the next 2 years. Epidemiologic data shows that, due to depression, 12,000 deaths occur annually in the United States in patients who survive their first heart attack. Many researchers now feel that pharmacologic and behavioral approaches have a potential to save thousands of these lives. Some of the antidepressant medications including the serotonin-specific reuptake inhibitors may be cardioprotective due to their ability to reduce the activity of the sympathetic nervous system. 21551 [car, psy] Typical summer clothing provides less`sun protection than a good sunscreen. Most lightweight cotton cloth increases the length of time one can remain in the sun without sunburn up to 5 to 9 times. When wet, a cotton T-shirt has a sun protective factor of 1 to 3. It is noted that silk and polished cotton will generally block the sun well. Normal skin can burn through polyester crepe. Dacron polyester generally provides good protection, while viscose rayon provides far less. A broader weave of fabric is less protective than a tighter weave. Irregular weaves have lower sun protective factors. Dark colors protect better than light colors because they absorb the ultraviolet light more completely. Sun protection is reduced when fabrics become wet, but how much depends on the weave and the color. Eighty percent of skin cancers occur on the head and neck and 1/3rd on the nose. A hat should be worn regularly and should have a brim that extends around the entire head or at least shades the face. Every inch of brim reduces lifetime skin cancer risk by 10%. There are several companies that have designed clothes specifically for sun protection. They include Frogskin, Inc. (800) 328-4440, Pearl Izumi Technical Wear (800) 777-7080, Sol Lite Active Wear (800) 552-9458, Solar Protective Factory, Inc. 800-SUN-BLOCK, Sun Precautions (800) 882-7860. 22087 [can] This study evaluated almost 14,000 residents of a retirement community for a 9 year follow-up period. There were 65 incident cases of pancreatic cancer discovered. Higher intakes of vegetables, fruit, beta-carotene and vitamin C were associated with a reduced risk of pancreatic cancer although none were statistically significant. The risk of pancreatic cancer decreased with increasing tea consumption but was unrelated to coffee. There was no stronger consistent association seen between either smoking or alcohol consumption and the risk of pancreatic cancer. There was a consistent and significant risk following cholecystectomy of pancreatic cancer. It is noted that the findings for the association between pancreatic cancer and cholecystectomy have been inconsistent. Cholecystokinin is a peptide hormone produced by the intestinal mucosa that stimulates the contraction of the gallbladder and pancreatic enzyme secretion. Cholecystokinin has been shown to be important in experimental pancreatic carcinogenesis. Endogenous cholecystokinin appears to be responsible for pancreatic growth following pancreatic juice diversion. Cholecystectomy may result in breakdown of the feedback controlling the release of cholecystokinin, and may precipitate an increased risk of pancreatic cancer by the trophic effect of cholecystokinin on the pancreatic acinar cells. 21608 [can] This study evaluated liquorice consumption at 50 and 100 gm and its effect on blood pressure in 30 normotensive individuals. One hundred gm of licorice daily in 30 individuals caused a significant rise in systolic blood pressure by a mean of 6.5 mm Hg and a fall in plasma potassium by .24 mmol/L. In a subgroup of 13 females consuming 50 gm of licorice daily there was also a significant rise in systolic blood pressure of 5.6 mm Hg. With the 100 gm licorice consumption there was a significant change in the cortisol/cortisone ratio in the urine which suggests inhibition of the 11B-hydroxysteroid dehydrogenase pathway in the kidneys. The data suggest that licorice-induced hypertension may be more common than has been previously thought. It is important for medical doctors to be aware of this effect in evaluating hypertensive individuals. Licorice appears to inhibit cortisol oxidase by glycyrrhetinic acid which is its active substance. Cortisol oxidase is part of the 11þ-hydroxysteroid dehydrogenase that converts the active glucocorticoid cortisol to the inactive steroid cortisone. Inhibition of this enzyme leads to an accumulation of cortisol in the distal nephron with increased access to minimal corticoid receptors. 22946 [car] In this study, authors noted that the content of vitamin D (ergocalciferol) found in different mushrooms varied significantly. Wild mushrooms contained the highest amounts of ergocalciferol. The contents of 25-hydroxy ergocalciferol were below the limit of detection in all mushrooms. The contribution of previtamin D2 to the total vitamin D activity was less than 10% of that of ergocalciferol in the mushroom species studied. Ninety percent of the total vitamin D content in the mushrooms studied was derived from ergocalciferol, whose content was very high in wild mushrooms, especially the genus Cantharellus. Since the annual consumption of mushrooms in Finland is only 0.61 kg/person, the average vitamin D intake from mushrooms is significantly low. Those whose diets contain an abundance of wild mushrooms may have a significant intake of vitamin D. 21669 [nut] Silicone injection for breast augmentation is still a common practice in Asia even though silicone injection-induced granulomas and associated malignancies have been reported. This is a case report of 24 women who had bilateral silicone injection granulomas in their breasts requiring subcutaneous mastectomy and immediate breast reconstruction. The average age of these patients was 37.5 years; granulomas were removed 3 to 20 years after the silicone injections. All the patient had some lumps; 21% had mastitis; 16% had dermatitis; none had palpable axillary lymph nodes. Subcutaneous mastectomies were done followed by immediate breast reconstruction with double-lumen silicone/saline implants or textured saline-filled implants. Two cases had wound infections as early complications and 2 cases developed hypertrophic scars. At 6 to 41 months follow-up 69% of the patients had Baker II and 31% of the patients had Baker III breast capsular contractures. 21940 [can, sur] This study evaluated 17 healthy individuals who were divided into 2 groups. One group of 8 received 400 ml of red wine per day for 2 weeks; a group of 9 received a similar amount of white wine. Red wine consumption for 2 weeks resulted in a 20% reduction in the likelihood of the plasma to undergo lipid peroxidation as determined by thiobarbituric acid reactive substances assay. Also, red wine consumption reduced the propensity of LDL to undergo lipid peroxidation as determined by a 46%, 72% and 54% decrease in the amount of TBARS, lipid peroxides in conjugated dienes in LDL respectively. Dietary consumption of white wine for 2 weeks resulted in a 34% increase in plasma propensity to undergo lipid peroxidation. There was also a 41% increase in the propensity of LDL to undergo lipid peroxidation. The antioxidant effect of dietary red wine on plasma lipid peroxidation was not secondary to the changes in plasma vitamin E or beta-carotene, but could be related to the elevation of polyphenol concentration in the plasma. 21937 [car] This study evaluated the relationship between diet and blood pressure in 705 men and women between 40 and 59 years of age. Individual intake of sodium was positively associated with systolic blood pressure. There was a positive association between dietary sodium or sodium/potassium found only in the group with calcium intake lower than the median. Daily intake of animal protein, urinary sulphate and certain amino acids were inversely associated with blood pressure. Taurine was found to be highest in the fisherman group and lowest in the farmer group. Lysine was lower in the farmer group. The group which had the highest intake of meat had the highest excretion of 3-methylhistidine, a marker of muscle metabolism; whereas the lowest was in the group that consumed the least amount of meat. Amino acids associated with animal protein intake tended to have an inverse relationship with diastolic or systolic blood pressure. This study lends support to the conclusion that dietary sodium increases blood pressure but dietary calcium and animal protein have a protective effect. 21374 [car] A grassroots association of organic farmers is forming an alliance with environmental and public interest organizations to promote organic foods to consumers. A grant has recently been given by the U.S. Department of Agriculture to help educate the consumer about the benefits of organic substances. Groups involved include the National Coalition Against the Misuse of Pesticides, the Community Nutrition Institute, Public Voice For Food and Health Policy, the Humane Society, World Wildlife Fund, and Mothers & Others. The focus of this group is to develop a plan for a centralized marketing cooperative to help small, organic farmers distribute their goods in the most efficient and effective ways. There will be research involving how to overcome the problems of inadequate supply, transportation and business skills. There is one national and 8 regional events planned for farmers to discuss marketing issues. 22539 [nut, foo] Ginkgolide B is a potent inhibitor of platelet activating factor. This was a randomized, double-blind, placebo-controlled trial in 104 patients who for 7 days 43 received a placebo, 29 received 240 mg per day of Ginkgolide B and 32 received 360 mg per day of Ginkgolide B. There was no statistical difference between the 3 groups for changes in rankin, kurtzke expanded disability status scale and hauser ambulation index scores. There was a trend in favor of the groups treated with Ginkgolide for a change of the Rankin AI scores. The authors conclude that Ginkgolide B is not an effective treatment of exacerbations of multiple sclerosis. Exacerbations of multiple sclerosis are associated with inflammation, white cell passage into the central nervous system and damage to the blood brain barrier. This damage is shown consistently on CT and MRI scans with contrast enhancement. Steroids are supposed to repair the blood brain barrier. Platelet activating factor is an important mediator of inflammation as a pivotal role in the vascular stage in the inflammatory process. Experimental studies have shown that Ginkgolide B is a compound that is a potent inhibitor of platelet activating factor and has been shown to prevent and treat experimental allergic encephalomyelitis, a widely used model of inflammatory demyelination that mimics the exacerbations of multiple sclerosis. The authors conclude that intravenous steroid courses are the only established effective treatment for acute exacerbation of multiple sclerosis. 22085 [neu] This article reviews elevations of blood manganese concentrations in 3 patients with biopsy-proven hepatic cirrhosis who had neurologic dysfunction. Magnetic resonance imaging noted accumulation of manganese in the brain which probably contributed to the neurologic dysfunction in patients with liver disease. These patients were between 49 and 65 years of age. It is noted that manganese toxicity and chronic liver disease are associated with very similar clinical, imaging and pathological abnormalities. Manganese toxicity is usually associated with increased intake from occupational exposure poisoning. The authors believe that manganese intoxication can also be caused by impaired elimination of normal dietary manganese. Impaired liver function can lead to manganese overload despite a normal intake. If manganese can be associated with neurologic dysfunction then therapies that diminish manganese intake or enhance its elimination may be beneficial. 21512 [gas, hep, tox] The director of the Bogalusa Heart Study is recommending universal cholesterol screening of children beginning at the age of 4 based on new findings. Selective screening results in underdetection of high cholesterol children. In evaluating over 8,000 children and their parents in the town of Bogalusa, it was found that parental evidence of cardiovascular disease rises as both children and their parents age (Circulation, 1995;91:365- 371). Offspring of parents who have a heart-attack history were significantly overweight after 10 years of age and showed elevated levels of total cholesterol, VLDL cholesterol, LDL cholesterol, insulin and glucose after 17 years of age regardless of their weight. Some of the researchers encourage looking not only for a family history of heart disease in the parents and grandparents, but also for all heart disease, especially premature heart disease or high cholesterol before the age of 55. The professor and chair in the Department of Epidemiology and Biostatistics at the University of California, San Francisco, Dr. Stephen B. Hulley, feels that cholesterol screening in children may do more harm than good. Psychologically having this "air" of adult disease and death hanging over them would be intense. They would be asked to eat differently from their peers at an age in which growing up is difficult enough. At best, universal childhood screening could be used as a "gentle one-time review" of risk factors and beneficial lifestyle. 21703 [car] This was a random sample of 4,000 members of a health maintenance organization in the Northwest looking at the prevalence of chronic fatigue syndrome. Seventy-seven percent of the members responded. Nineteen percent reported chronic fatigue. Of these 66% had a medical or psychiatric condition that could account for the fatigue. In 37% with chronic fatigue only 3 met the CDC criteria for chronic fatigue syndrome. The remaining 71 were defined as having chronic fatigue alone. The estimated crude point prevalence of the syndrome in this community ranged from 75 to 276 cases per 100,000 persons. The point prevalence of chronic fatigue alone was strikingly higher, ranging from 1,775 to 6,321 cases per 100,000 members. 22926 [met] In evaluating 11 normal-weight bulimia nervosa females there was significantly higher serum levels of free testosterone than age- matched controls. The possibility that women with higher androgen levels are more susceptible to disorders characterized by poor impulse control, such as bulimia nervosa and PMS, needs further evaluation. It is noted that a report of women suffering from obsessive-compulsive disorder, which is a disorder of impaired impulse control, responded to a serotonin reuptake inhibitor. This condition may also be treated with the testosterone antagonist cyproterone acetate. 21357 [end, gyn, nut] This study evaluated 294 probable Alzheimer's disease cases compared to 300 nondemented controls of similar age and gender mean age of 78.5 years. There was a modest association between Alzheimer's disease and depression after adjusting for certain variables. There was an odds ratio for depression of 2.0 occurring more than 10 years before the onset of dementia symptoms and an odds ratio of .9 for depression onset within 10 years of onset of dementia symptoms. Depressive episodes occurring well before dementia symptom onset appeared to increase the risk of Alzheimer's disease. 22787 [neu, psy] This is a review article noting that the recent popular debate regarding trans fatty acids has lost sight of the real problem, that is, saturated fats. The concern is that transfatty acids: 1. Behave like saturated fats. 2. Independently increase the risk to coronary heart disease. 3. May cause other undefined harm to health. In Australia, there is really a low amount of trans fatty acids compared to other western countries; the question is how this country should incorporate trans fatty acids. Normally polyunsaturated fatty acids are in the cis configuration at the carbon double bond which means the hydrogen atoms point in the same direction. In the trans fatty acids the atoms point in opposite directions. A small change like this in oleic acid can reverse its cholesterol lowering potential. Trans fatty acids are produced during the hydrogenation of oils in the manufacture of margarines. It is noted that þ of our dietary trans fatty acids are derived from dairy, beef and sheep fat. Two percent of the total energy intake in the Australian diet is from trans fatty acids compared with 15% from saturated fats; one-third of this is from ruminant sources. Consumption of margarine and other hardened oil products provides approximately 1/10th of the fatty acids likely to raise plasma cholesterol. The author feels that switching from margarines to butter is a þridiculousþ suggestion by some experts. The polyunsaturated fatty acids and monounsaturated fatty acid structures are considerably superior to those of butter with regards to their influence on LDL cholesterol. In the same breath the author suggests that the industry needs to come up with technologies that do not add trans fatty acids to the contents of foods. Trans fatty acids should be counted as saturated fatty acids in calculating the polyunsaturated to unsaturated fats in margarines. The author feels that too much has been stated regarding the claim that trans fatty acids raise the risk to coronary heart disease. In conclusion the author feels that patients should be told that trans fatty acids will raise LDL cholesterol concentrations and some of this will come from margarines and products made from margarines. At present we are far from knowing that the small amount of trans fatty acids in our food supply can cause heart disease other than by raising LDL cholesterol concentrations. There is no other proved adverse consequences of trans fatty acids. In general we should eat less fat, avoiding undefined sources of fat from fast foods and other quick-take-out establishments. Mostly, saturated fat should be avoided; eating butter is not safer than quality poly or monomargarines. 21360 [car, nut] This study was done to evaluate the role of endogenous hydrogen peroxide in cardiac depression and cytotoxicity during hemorrhagic shock and reinfusion. In this dog model cardiac function and contractility were depressed while plasma creatine kinase, creatine kinase-MB activity and lactate increased during shock. Reinfusion after 2 hours tended to return hemodynamic parameters of plasma lactate levels toward control values. Plasma creatine kinase and CK-MB and creatine kinase-MB and polymorphonuclear leukocytes oxygen radical producing activity increased further. Cardiac malondialdehyde concentrations increased after shock and reinfusion. This suggests oxidative damage. Pretreatment with catalase attenuated the adverse effects of shock and reinfusion on the cardiovascular function and contractility. Catalase's protection was not complete. The results suggest that hydrogen peroxide may partly be involved in the deterioration of cardiac function and cellular injury during hemorrhagic shock and reinfusion. 22218 [car, cri, hem] Since the 1960s and 1970s the observation in the Greenland Eskimos of omega-3 fatty acids shifted research towards that group. The Seven Country Study showed an average saturated fat intake to be strongly related to 15 years' mortality from coronary heart disease. These results suggest that a highly saturated fat intake results in a higher mortality from coronary heart disease. In several studies there was no association found between the intake of different fatty acids and coronary heart disease. In the Western Electric Study there was a significant inverse association between polyunsaturated fatty acid intake and coronary heart disease. The studies of Dr. Dyerberg in the 1970s showed that the average intake of omega-3 polyunsaturated fatty acids was 2 to 3 times higher than the intake of omega-6 fatty acids. The diet of the Eskimos were characterized by 39% from fat with a low amount of saturated fat and a high polyunsaturated to saturated fat ratio. The intake of monounsaturated fats was also high. Compared to Danish mortality data only 3 cases of acute myocardial infarction were found when 40 cases were to be expected. The data was exciting in the Eskimos but it did not justify a conclusion in the causal relationship to ischemic heart disease. An analysis of the Zupthon Study from Holland showed that fish consumption at the start of the study was inversely related to mortality from coronary heart disease in the period 10 to 20 years later. Mortality from coronary heart disease is about 2 times lower among males eating at least 30 gm of fish per day compared with non-eaters. The dose response relationship was observed between 0 and 30 gm of fish per day. In 1957 the Western Electric Study evaluating 2,000 males in Chicago showed an inverse relationship found between fish consumption and coronary heart disease during 25 years of follow- up. This was also found in a Swedish study. Two other studies did not confirm the relationship with fish consumption. In the large American MRFIT Study dietary fish intake has been followed and omega-3 fatty acids have been reported to be inversely related to total mortality and mortality from ischemic heart disease. Epidemiologic data in Alaska showed the Eskimos have a substantially lower extent of atherosclerosis as compared to nonnative Alaskans. 22760 [car] This study evaluated the relationship between fasting insulin levels and cardiovascular risk in 390 men between 70 and 89 years of age. The fasting insulin levels were significantly associated with levels of glucose, triglycerides, uric acid, serum albumin, creatinine, fibrinogen and heart rate. There was an inverse association between high density lipoprotein cholesterol and factor VII activity with insulin levels. Men who had elevated fasting insulin levels greater than 80 pmol/L had significantly higher incidence of coronary heart disease, particularly myocardial infarction. This was independent of other potentially confounding variables. There was no association seen between fasting insulin levels and blood pressure in general. The authors conclude that fasting insulin levels are an important predictor of coronary heart disease in elderly men. 21552 [car, end] This study evaluated in 39 patients with insulin-dependent diabetes compared to 34 controls levels of taurine before and after 1.5 gm of oral taurine per day for 90 days. Plasma and platelet taurine concentrations were lower in diabetic patients than control subjects. After oral supplementation there was an increase in both plasma and platelet taurine levels which increased significantly in diabetics reaching the mean value of healthy control subjects. The necessary dose of arachidonic acid needed for the platelets to aggregate was significantly lower in the diabetic patients than in the control subjects. After taurine supplementation in diabetic patients it equaled the mean value for the healthy control subjects. Taurine reduced platelet aggregation in diabetic patients in a dose dependent manner whereas 10 mmol of taurine/l did not modify aggregation in healthy subjects. Taurine may have a direct cytoprotective effect in diabetes even though the mechanisms of taurine-induced decrease in platelet aggregation is still unknown. It has an antioxidant capability that may protect cell membranes as well as other cellular components. Oral administration of taurine brings about a decrease in platelet aggregation. This may reduce diabetic complications such as micro and macroangiopathies which are associated with increased platelet aggregation. This data shows that normal concentrations of taurine could be of importance in restoring the normal clotting disorder and consequently in preventing vascular complications in insulin- dependent diabetes mellitus. 22307 [car, end] A retrospective chart review of children at a county hospital clinic was undertaken and it was found that lead level results were available for 175 children. The average lead level was 4.3 ug/dL for Pakistani/Indian children not using eye cosmetics and 12.9 ug/dL for those using the products. An evaluation of some of the eye cosmetics revealed high lead content. Use of eye cosmetics from Pakistan were reported to be strongly correlated with elevated blood lead levels. Education regarding low level lead toxicity and avoidance of substances containing lead is encouraged specifically for these types of populations. It is noted that importation of leaded eye cosmetics is prohibited by law but it obviously has not been effective in protecting children. 22148 [tox] This article reviews red and white wine and how particularly red wine may trigger a migraine headache. It could be that dietary migraine sufferers may already have a reduced detoxicating ability, which allows noxious phenols to enter the blood stream in sufficient concentrations to provoke a migraine attack. Ingestion of powerful inhibitors of phenolsulphotransferase such as that in red wine could facilitate this process. Red wine also is known to strongly inhibit the binding of 5 hydroxytryptophan to 5 hydroxytryptophan1 receptors. White wine possesses this ability to a lesser extent. This is preliminary work. Sumatriptan, which is a powerful antimigraine medication, is known to strongly act on these receptors. Adversely red wine has been shown to a selective MAO A inhibitor and white wine possess selective inhibition for human MAO B. 22896 [neu] This study evaluated zinc metabolism in 166 pregnant females. Those who had lower plasma zinc levels and raised maternal serum alpha-fetoprotein delivered more low birth weight offspring than those with normal maternal serum alpha-fetoprotein due to both a shorter pregnancy and slower intrauterine growth. 21600 [nut, obs] This is a review of the ISIS 4 study on magnesium and acute myocardial infarction. The author's synopsis states that there are no grounds for magnesium's routine use in myocardial infarction. The authors note that the results of this study are very disappointing. At 35 days of follow-up there had been 2,216 deaths among the 29,011 patients who received magnesium compared to 2,103 among the 2,939 patients who received the standard treatment. With regards to the argument that delays in giving magnesium after thrombolytic treatment could have confounded the results of the ISIS 4 the authors note that after further analysis of the ISIS 4 showed there was no significant benefit among the 10,252 patients randomized within 3 hours of onset of myocardial infarction. The authors feel that a meta-analysis of small trials is not a replacement for large, carefully randomized conducted trials. Also, since most treatments produce either no effect or at least only moderate effects of major outcomes such as mortality, investigators should be skeptical of results obtained which substantially deviate from what is expected. Thoroughly definitive trials should demand levels of evidence that are statistically more reliable. 22110 [car] This is an extensive review article on the role of alcohol in cancer. Alcohol intake appears not to increase the risk of cancer of the lung, bladder, prostate, stomach, ovary, endometrium or melanoma. Alcohol may be a weak causal factor for pancreatic cancer. Alcohol consumption continues to increase the risk for cancer to the mouth, pharynx, larynx, esophagus and liver. The effect of alcohol consumption on cancer of the breast and the large bowel is not clear. 22106 [can] This study evaluated 30 neonates born at 30 weeks who received human milk or were randomized to 3 different formulas. The first formula was based on corn oil. The second was based on soy oil supplied with alpha linolenic acid and formula C was similar to B with added marine oil providing docosahexaenoic acid. The rod photoreceptor test demonstrated higher thresholds and decreased sensitivity in the omega-3 fatty acid deficiency patients. Visual acuity also showed improved function of the brain cortex in human milk and group C infants at follow-up of 57 weeks. These results suggest that omega-3 fatty acids are needed for optimal development of the visual system. Supply of essential fatty acids during early life influences the maturation of the retina and the brain. 21804 [peds] The Center For Science in the Public Interest has recommended that there be a tax increase on pesticides. American farmers spend approximately $15 billion a year on pesticides and chemical fertilizers to grow crops. Pesticides and fertilizers help deliver an abundant and inexpensive food supply and control weeds and pests in cities. But some environmental health problems from the use of pesticide are estimated to cost as much as $8 billion per year. Chemical pesticides impact water quality, food safety, farm worker safety and wildlife habitats. Costs of the pesticides are borne by farmers who are exposed to high levels of these chemicals. Consumers may suffer from exposure to the chemicals in their diet and taxpayers, many times, have to pay for the clean-up costs. Raising small fees on pesticides and fertilizer soils could provide revenues to fund programs designed to promote farming practices that reduce the need for the use of harmful chemicals. An opinion poll in January 1995 demonstrated that consumers strongly support charging a small amount more for pesticides and to have state and federal agricultural programs teach farming methods which reduce overall pesticide use. The taxes and registration fees on pesticides should be increased modestly at the state level. A 1% increase in pesticide tax would raise 85 million dollars annually. In 1995, farm bills should include increased funding for research and programs to help farmers reduce their pesticide and fertilizer usage. According to the EPA approximately 20,000 pesticide products are registered for use in the United States. There are 3 million classes of pesticides, herbicides, insecticides and fungicides. Herbicides are the largest group. Approximately 90% of herbicides are applied to four crops which include corn, soybean, cotton and wheat. Farmers spent $7.4 billion on commercial fertilizers and $6.1 billion on pesticides in 1991. Fertilizer components include nitrogen, phosphate and potash. Nitrogen fertilizers are approximately half of the fertilizers used and are applied to over 90% of the corn, cotton, potato and rice acres and 60% of the wheat acres. Phosphate and potash fertilizers are used extensively to produce vegetables, corn, rice and wheat. States using the most nitrogen fertilizers are Iowa, Illinois, Nebraska and Texas. 22538 [pes] This is a review article on the role of homocysteine lowering by specific vitamins and its effect on cardiovascular disease. There is rapidly accumulating evidence that moderate levels of elevated homocysteine are an independent risk factor for cardiovascular disease. All but 5 of 47 studies, including a total of more than 15,000 investigated patients and controls, support this issue. Both basal elevated levels of homocysteine and hyperhomocysteinemia revealed by a methionine load are markers for increased cardiovascular risk. The finding of a dose-response relationship between plasma homocysteine concentration, over its full range, and the relative risk for the prevalence or severity of cardiovascular disease strongly supports causality. Dietary vitamins B6, B12, folate and their synthetic oral counterparts pyridoxine hydrochloride, cyanocobalamin and folic acid serve as precursors of the cofactors for homocysteine metabolism, Pyridoxal 5 Phosphate, methylcobalamin and methyltetrahydrofolate respectively. In man, vitamin B6 deficiency does not seem to result in basal hyperhomocysteinemia. Folate and vitamin B12 deficiency may result in considerable hyperhomocysteinemia which is rapidly normalized after replenishment of the deficient vitamin. Even within the normal ranges, levels of serum or red cell folate and serum vitamin B12 are strong determinants of plasma homocysteine concentrations. In untreated cases of genetically caused severe hyperhomocysteinemias (homocystinuria), life threatening cardiovascular events are frequent. In general, cofactor supplementation for homocysteine metabolism results in considerable decreases of plasma homocysteine concentration. Renal insufficiency results in moderate hyperhomocysteinemia and accelerated atherosclerosis. Several studies have shown that oral treatment with folic acid at 5 to 10 mg per day reduces renal hyperhomocysteinemia by a factor of 30 to 60%. Oral vitamin B6 has no homocysteine lowering effect in this condition. In fact, the authors found that pyridoxine treatment at 300 mg per day for 18 weeks in uremic patients with low plasma pyridoxal phosphate levels lead to significantly increased plasma homocysteine concentrations. In 2 studies which included 28 non- vitamin deficient healthy subjects, mostly with normal plasma homocysteine levels folic acid at 5 mg per day for 2 to 4 weeks resulted in lowering of homocysteine levels in all but 2 of the individuals. Reductions were in the average larger than 30% and were most marked with high homocysteine levels. Oral treatment over 2 weeks with pyridoxine at 40 mg per day or vitamin B12 at 1 mg per day had no homocysteine lowering effect. In another study, vitamin B6 at 120 mg a day had no effect over 6 weeks on plasma homocysteine concentrations in 16 healthy subjects. The authors propose that the homocysteine lowering effect of folic acid in nonfolate deficient subjects is from the excess folic acid after conversion to methyl tetrahydrofolate increases the rate by which homocysteine is remethylated to methionine. In contrast, excess B12 and folic acid will not decrease plasma homocysteine and unless deficiency is present as these vitamins serve as coenzymes, not as cosubstrates as does methyltetrahydrofolate. In 2 recent studies of patients with vascular disease and hyperhomocysteinemia and 1 study in normal normohomocysteinemic patients the combination of vitamin B6 at 100 to 250 mg per day and folic acid at 5 to 10 mg per day reduced plasma homocysteine levels by a mean of 51, 38 and 30% respectively. In a group of consecutive patients with acute myocardial infarction of whom most were normohomocysteinemic and all had normal serum folate levels, we found that 2.5 mg and 10 mg of folic acid over 6 weeks had a similar homocysteine lowering effect in both plasma homocysteine effect. In both groups plasma homocysteine was reduced by a mean of 27%. Reductions were seen in all but 2 patients, both with low homocysteine values. With few exceptions the response to folic acid was proportional to the pretreatment homocysteine levels. Hyperhomocysteinemia due to vitamin B12 deficiency does not respond to folic acid therapy. It has been shown that men with moderate hyperhomocysteinemia in most cases had suboptimal plasma vitamin B12 and folate levels. Such men were in a 6 week trial either given folic acid at .65 mg per day, pyridoxine at 10 mg per day or cyanocobalamin at .4 mg per day or a combination of these vitamins. Most but not all responded to the folic acid. Pyridoxine had no homocysteine lowering effect in this study whereas cyanocobalamin decreased plasma homocysteine by a mean of 15%. All responded to the combination by a mean of homocysteine reduction of 50% though homocysteine values were not normalized in all subjects during this short trial. There are recent results showing that high dose parenteral administration of cobalamin decreases plasma homocysteine in subjects with normal vitamin B12 levels. There have been several studies which show that patients with premature cardiovascular disease frequently respond to oral methionine loads of 100 mg per kg of body weight with abnormally high increases in plasma homocysteine concentrations. This may be more suggestive of a vitamin B6 deficiency compared to an elevated basal homocysteine concentrations which may be more indicative of vitamin B12 and folic acid deficiency which effects homocysteine remethylation. Several studies have shown that pyridoxine at 100 to 250 mg per day improves abnormal methionine loading tests in many but not all patients. With a combination of vitamin B6 at 100 to 250 mg per day and folic acid 5 to 10 mg per day all the patients responded and the abnormality was mostly normalized. Methionine rich meals normally cause slight increases in plasma homocysteine concentrations. It is quite possible that subjects with abnormal methionine loading tests are also responding abnormally to methionine rich meals leading to transient periods of hyperhomocysteinemia which could be normalized with combined pyridoxine and folic acid therapy. For several reasons it appears wise to combine folic acid with vitamin B12. Folic acid seems to reduce all but low homocysteine levels. Cyanocobalamin will probably secure the full responsiveness of folic acid. In vitamin B12 deficiency erroneous treatment with folic acid may correct the hematologic abnormalities but result in a deterioration of vitamin B12 neuropathy. Before starting therapy vitamin B12 deficiency must be excluded and the combination must contain a dose of cyanocobalamin high enough to prevent the occurrence of vitamin B12 deficiency even if complete intrinsic factor deficiency develops during the course of therapy. At least .2 mg of cyanocobalamin need to be administered. For intervention studies in cardiovascular disease a combination of 1 mg of folic acid and .4 mg of cyanocobalamin is probably sufficient for effective homocysteine lowering. This combination will probably be innocuous and also normalized hyperhomocysteinemia in most patients and reduce the normal homocysteine values leading to a shift of the entire homocysteine distribution towards lower values. This is important because there appears to be a relationship between plasma homocysteine concentrations and the risk of cardiovascular disease. 22074 [car] This study evaluated 272 men and women with chronic renal failure who were compared to 272 controls. There was a significant increased risk of chronic renal failure found for exposure to lead, copper, chromium, tin, mercury, welding fumes, silicon containing compounds, grain dust and oxygenated hydrocarbons. Occupational exposures were high among patients with diabetic nephropathy. This data confirms that additional occupational exposures may be important in the development of chronic renal failure. The role of grain dust and the association between the exposure and diabetic nephropathy warrant further study. 22578 [nep] This study evaluated 68 Alzheimer's disease patients, 46 who were living and 22 who were deceased, and 34 nondemented control subjects. Head injury was reported in 20 of the Alzheimer's disease patients (29%) and in 1 control subject (2.9%). Twenty percent of the familial and 43.5% of the sporadic Alzheimer's disease cases reportedly had a head injury prior to death. Head injury had no effect on the age of dementia onset in subjects. This data suggests that head injury may be a predisposing factor to Alzheimer's disease. 22711 [neu, psy] This study sent out a questionnaire to 150 cystic fibrosis patients of which 80 returned the survey. Forty-seven percent followed the clinic's recommendation. In those patients not taking extra supplements serum vitamin A and E levels varied widely though most were in the normal range. Only 25% of those that responded had known insurance coverage for vitamins. Of those with minimal pulmonary disease, with a forced vital capacity of greater than 70% of predicted, they were more likely to take vitamins than those with moderate or severe disease. Malabsorption and poor consumption of vitamins A and E may result in low serum vitamin A and E levels especially in patients with moderate to severe lung disease. The authors concluded that health professionals should encourage the use of multivitamin supplements in patients with cystic fibrosis even though all the questions regarding optimal therapy have not been answered. Primary care pediatricians who care for children with cystic fibrosis should inquire about the use of vitamins and encourage them to be consistent in the use of this preventive modality. Specialty physicians who care for children with cystic fibrosis should screen for vitamin A and E deficiency on a yearly basis and should share this information with the patient and also the primary care provider. 22345 [nut, pul] Out of every 10,000 hospital admissions 7 to 21 are admitted for renal stone disease and close to 80% of the kidney stones are composed mainly of calcium oxalate. Regular black tea is known to have high oxalate concentrations and its consumption without adding milk has been shown to increase urinary oxalate concentrations. Herbal teas often contain ingredients that are known to contain oxalate such as citrus peels, berries and leaves. This study measured oxalate concentrations of herbal teas to determine whether herbal teas would be an acceptable alternative to reduce the risk to calcium oxalate stones. The oxalate content of herbal teas and coffee ranged from 7 to 32 times less than black tea. The green oolong tea measured in this study contained 1.5 to 3 times less oxalate than black tea steeped for 5 minutes. The difference has to do with the concentrations between green tea and black tea in the tea bag. When expressed oxalate per gram of tea oxalate levels in the green tea were similar to brands of black tea and half concentrations of the other. When black teas were steeped for 1 minute the oxalate content was less than when steeped for 5 minutes. Vigorous stirring of tea steeped for 1 minute caused a marked increase in oxalate concentration. Fourteen commonly available herbal teas that were infused for 5 minutes had low oxalate content even when compared to black tea that was only infused for 1 minute. Coffee prepared from the drip method was also found to have a low oxalate content similar to that of herbal tea. These may be reasonable alternatives for those with a history of calcium oxalate formation. 22264 [nep] There will be a presidential commission on nutraceuticals; these are plant components with pharmacologic activities that need to be regulated. The commission will be established under the Dietary Supplement Health and Education Act of 1994, which defines dietary supplements, regulates their health claims and labeling, and provides for good manufacturing practices. The act defines supplements as any product that contains 1 or more dietary ingredients such as vitamins, herbs or other botanicals, amino acids or ingredients used to supplement the diet. Under this act, if a nutraceutical is marketed as a dietary supplement and is later approved as a new drug, it may remain on the market as a dietary supplement. But if the nutraceutical is approved as a new drug before being marketed as a dietary supplement, it may not later be marketed as a dietary supplement without FDA approval. With this kind of regulatory protection, pharmaceutical companies envision the potential market for nutraceuticals in the billions of dollars annually. Three key plants containing compounds which have pharmacologic activities include licorice, soy and garlic. Dr. Baker from the University of California at San Diego notes similarities between steroid hormones and licorice-derived compounds called flavonoids. Some of the compounds found in licorice could have a benefit on depression. At levels of 500 ug/mL and lower, glycyrrhizin and related compounds of licorice inhibit the formation of giant cells by HIV. In HIV positive patients, giant cells are one of the signals that infection is moving from latency to active AIDS. About 400 compounds have been isolated from the licorice plant. Soy is a source of vitamin E. Garlic extract has been shown to boost immune function and has antioxidant properties, extends the survival of cultured neurons, appears to protect against cardiotoxicity and may lower cholesterol levels. 22018 [nut] This article notes that there is little evidence that dietary carotenoids can improve vitamin A status. This was a 12-week study of 57 patients who received stir-fried vegetables, a second group of 62 patients who received a wafer enriched with beta-carotene, iron, vitamin C and folic acid and a third who received a nonenriched wafer to control for supplementary additional energy intake. These individuals were females who were breast feeding a child 3 to 17 months who had low hemoglobin concentrations less than 130 g/L. In the enriched wafer group there were increases in serum retinol, breast milk retinol and serum beta-carotene. These changes differed significantly from those in the other 2 groups in which the only significant changes were small increases in breast milk, retinol in the control-wafer group and in serum beta-carotene in the vegetable group. Changes in iron were similar in all 3 groups. In this study a daily portion of dark green leafy vegetables did not improve vitamin A status. Trying to combat vitamin A deficiency by increasing the consumption of provitamin A, carotenoids from vegetables may not have the desired effect and needs to be re-examined. 22816 [neu] Sixty-eight percent of 38 Pakistani women and 17% of 38 Norwegian women in their 18th week of pregnancy were found to have ferritin levels below 12 ug/l and a highly significant difference in serum ferritin. A highly significant difference in serum ferritin was found between the groups. Only 1 of the Pakistani and 7 of the Norwegian women were supplemented with iron and there was no significant difference in dietary intake of heme iron, non-heme iron, organic fiber, tea, vitamin C, meat, and cereals. The estimated inositol hexophosphate or phytate and inositol pentaphosphate which are inhibitors of iron absorption, were much higher in the Pakistani diet (1175 umol/d) compared to the Norwegian diet at 507 umol/d. Iron deficiency appears to be more common among pregnant Pakistani's than Norwegians and one of the main reasons is a combination of higher parity and less common use of iron in pregnancy and the higher phytate content of the Pakistani diet. 22922 [nut, gyn, obs] This is a report on two cases of women whose PMS and migraine headaches improved with vitamin D and calcium therapy. The first case was a 33-year-old female who had frequent migraine headaches and PMS. The second case was a 40-year-old female with a history of migraines with aura and a 10-year history of PMS. The first patient was treated with a combination of cholecalciferol at 1600 IU and elemental calcium at 1200 mg per day because of low vitamin D levels. Within 2 months the migraine headache attacks were significantly improved, along her PMS symptoms. A repeat of her 25 hydroxyvitamin D level showed a significant increase into the low normal range of 17.3 ng/mL. Treatment with a higher oral dose of vitamin D2 at 50,000 units per week resulted in elimination of her PMS symptoms. In the second case vitamin D and calcium levels were normal but the patient was placed on cholecalciferol 1,200 I.U. as well as 1,200 mg of elemental calcium per day for 3 months. There was a significant reduction in her migraine headaches as well as her PMS symptoms. Her 25 hydroxyvitamin D level was shown to increase with supplementation. According to the patient further migraine attacks were aborted immediately when chewing the equivalent of 1,200 to 1,600 mg of elemental calcium. The author suggests that 25 hydroxyvitamin D levels should be considered in the evaluation of women with menstrual migraine headaches. 21589 [gyn, neu] This study evaluated iron stores in 847 men and women between 40 and 79 years of age. Ferritin emerged as a strong indicator of carotid artery disease in both sexes between 40 and 59 years with an odds ratio of 1.54 per 100 ug/l. The predictive value of ferritin was found to be synergistic with that of hypercholesterolemia. Variations in body iron stores between the sexes may partly explain the sex difference in the expression of carotid atherosclerosis. In those greater than 60 years of age the predictive significance of ferritin was found to decrease parallel to that of apolipoprotein B. This current data suggests a role for body iron in early atherogenesis. 21894 [car] In this study, the rhizomes of Curcuma longa showed strong preventive activity against carbon tetracwhloride-induced liver injury in vivo and in vitro. The liver-protective effects of some analogs of ferulic acid and p-coumaric acid are the probable metabolites of curcuminoids, which have benefit. Curcuma longa has been used as an aromatic stomachic and diuretic as well as a remedy for jaundice in Oriental medicine. 22527 [gas] This study evaluated 3 gm of eicosapentaenoic acid in a double- blind, randomized, multi-center study that was given from 12 to 14 weeks of gestation onwards. Sixty-three subjects with a history of intrauterine growth retardation with or without pregnancy-induced hypertension in the previous pregnancy were evaluated. One-third of the women developed pregnancy-induced hypertension and þ of the infants had a birth weight below the 10th centile. There was no difference between the placebo and in the eicosapentaenoic acid group. This study suggests that 3 gm of eicosapentaenoic acid daily does not prevent the recurrence of intrauterine growth retardation or pregnancy induced-hypertension in a high risk population. Future studies should utilize higher doses of EPA preferably in combination with a diet low in arachidonic acid. 22189 [obs, ped] Sources of lead exposure to children include lead based paint, lead contaminated soil, house dust, food and drinking water, leaded gasoline, parental occupations and hobbies, industrial emissions, lead-glazed ceramicware, lead-solder cans and some traditional medicines and cosmetics. Ingestion is a primary route of exposure to children. A survey of 43 directors of medical school affiliated lead clinics located in 18 cities concluded that: 1. There is a wide range of blood lead levels for which chelation therapy is recommended. 2. The majority of children with blood lead levels of 1.21 umol/l to 2.17 umol/l (25 ug/dl to 45 ug/dl) with negative CaEDTA provocation tests do not receive chelation therapy. Oral chelating agents are used in the minority of clinics. There is no common approach for the treatment of lead toxicity as present. In the majority of pediatric centers current management of blood lead elevation did not appear to reflect the new information regarding the effects and treatment of lead poisoning. It is noted that meso- 2,3-dimercaptosuccinic acid (succimer) is a promising new oral treatment for lead poisoning. Succimer is a chemical analog of British antilewisite that forms water soluble complexes with lead that are excreted by the kidneys. Succimer is approved only for the treatment of children with blood lead levels greater than 2.17 umol/l (45 ug/dl). Succimer is equally effective as lowering lead levels in children with levels less than 2.17 umol/l (45 ug/dl). The drug has several advantages in that it is orally administered; it is well tolerated with infrequent side effects and it is a relatively specific chelating agent for lead producing less undesired excretion of zinc, copper, iron and calcium EDTA. Health and nutritional counseling is probably the most cost effective means to approach children with exposures less than .97 umol/l (20 ug/dl). Children with lead levels greater than .97 umol/L (20 ug/dL) should receive more involved intervention. Intervention should include reducing the child's body burden and absorption of lead, chelation therapy, treating calcium and iron deficiency and identifying and removing sources of lead. 22187 [env, tox] This study evaluated 10 infants with persistent pulmonary hypertension who were not receiving protein or amino acids for at least 24 hours and compared their plasma arginine concentrations to 8 control infants without persistent pulmonary hypertension receiving similar nutrition. Plasma arginine concentrations were 32 and 52 umol/l in infants with persistent pulmonary hypertension and control infants respectively. There were no other significant differences in the concentration of plasma amino acids. Infants with persistent pulmonary hypertension who were later treated with amino acid infusions had plasma arginine concentrations at 115 umol/l. It is noted that nitric oxide, which has shown some benefit in the treatment of infants with persistent pulmonary hypertension, is synthesized in the body from the amino acid L-arginine. 21408 [ped, pul] Eighty-four patients with primary sclerosing cholangitis randomly received 1 mg of Colchicine daily in 44 patients or a placebo in 40 in a double-blind 3-year study. There was no evidence of a beneficial effect of Colchicine on survival symptoms, serum biochemistry or liver histology in the patients with primary sclerosing cholangitis. 22805 [gas] This is an extensive review article on the role of recycling drinking water from secondary waste water. Based on the studies, the authors concluded that properly treated secondary waste water can be recycled into safe drinking water for public consumption. 21505 [env, tox] This is a case report of a 51-year-old female with a 1 year history of episodic right upper quadrant pain and a recent onset of jaundice who was admitted for a cholecystectomy. She eventually developed oliguria and her serum urea nitrogen and creatinine levels increased to 21.7 mmol/L of urea and 750 umol/L respectively. She was diagnosed as having rapidly progressive glomerulonephritis. Following a short course of hemodialysis the patient's renal function improved. It was noted that she had been on a Chinese herbal medicine, Tung Shueh pills. She had been taking 8 herbal pills daily for 4 weeks. Chemical analysis of the Chinese herbs found that mefenamic acid and diazepam were listed as nonlabeled adulterants. Chemical analysis confirmed the presence of mefenamic acid and diazepam 0.4 mg per pill. The herbal tea she was taking contained caffeine. Renal toxicity associated with mefenamic acid is well documented. Ingredients reported in herbal medicines that are associated with renal failure include phenylbutazone and aristolochic acid. This patient developed acute renal failure following deliberate contamination of an illegally imported herbal medicine with nonlabeled adulterants. Even though adverse drug reactions to herbal medications are relatively uncommon and frequently mild, some reactions can be either life threatening or fatal. The public needs to be aware that these preparations are not entirely innocuous. Physicians need to inquire about herbal medicines when evaluating patients with potential adverse drug reactions. 21683 [her] Many plants contain natural estrogens called phytoestrogens. These compounds have estrogenic agonists-antagonist properties that are organ specific. The potential beneficial activity of estrogenic isoflavones from soy in adults appears to depend on the mixed agonist-antagonist properties of these compounds in part. It also appears to be derived from important biochemical actions of isoflavones such as inhibition of protein kinases. An alternative explanation is that these isoflavones and more specifically the dephenolic compounds may cause cellular effects through a unique orphan receptor that is distinct from well recognized nuclear receptors. There is no epidemiologic evidence of the potential developmental effects of phytoestrogens on the genital tract in populations who consumed large quantities of phytoestrogen rich soy foods, though one needs to be aware of the teratogenic effects of diethylstilbestrol on the developing genital tract of both male and female human fetuses. The authors are unaware of any data indicating the high consumption of soy foods or soy estrogens result in early puberty in human females or later puberty in males. In animal models certain dietary phytoestrogens can disrupt reproductive processes. A study of the dietary effects of phytoestrogens on fertility and reproductive endocrine process in human primates and need to be confirmed. It is known that Asian women who have the lowest rates of breast cancer consume 30 to 50 times more soy products than the American women. The differences in urinary excretion of phytoestrogens between Asian American women are 2,000 to 3,000 nmol/24 hours of genistein and daidzein for Asian women and in American women it is 30 to 40 nmol/24 hours. There is both observational and experimental evidence that phytoestrogens protect against prostate cancer. There is some experimental basis that phytoestrogens are protective against colon cancer. The theory that phytoestrogens may protect against the development of coronary artery atherosclerosis is based on well established evidence that endogenous estrogen protects women from coronary heart disease relative to men at the same age. The fact that there are low rates of coronary heart disease in Asian women is another support of a factor of the phytoestrogen concept protective concept. There is a consensus that dietary soy protein is antiatherogenic compared with a variety of animal proteins. There is some interest in soybean estrogens preventing postmenopausal bone loss in osteoporosis. In a recent study a low dose, not a high dose, of genistien was equivalent to conjugated equine estrogens in maintaining bone mass in a rat model. Further evidence of the bone-protective effect of genistein is increasingly wide use of structurally similar compounds ipriflavone in preventing bone loss menopausal women. 22266 [end] This study evaluated the plasma cholesterol response to an isoenergetic substitution of a milk chocolate bar (46 grams) given daily for a high carbohydrate snack in healthy men on the Step I National Cholesterol Education Program/American Heart Association Diet. Forty-two normal cholesterolemic men were fed the Step I diet for 21 days followed by a 27 day experimental period in which they consumed the same diet plus either a milk chocolate bar or a high carbohydrate snack. After this they consumed the "run-in" diet for 21 days followed by the other snack for 27 days. When the subjects consumed the milk chocolate bar instead of the high carbohydrate snack, high density lipoprotein cholesterol was .08 mmol/l higher and plasma triglycerides were .06 mmol lower. Substitution of the milk chocolate bar for a high carbohydrate snack did not adversely effect low density lipoprotein cholesterol response to the Step I diet despite an increase in total fat and saturated fatty acid content of the diet. This may be due to the fact that the chocolate contains stearic acid. This data suggests that it is not necessary to reduce the stearic acid content of cholesterol lowering diets. This will lead to fewer restrictions on certain foods and provide greater flexibility in planning diets that lower cholesterol. In a broader context this suggests that a food relatively high in fat containing the appropriate fatty acid profiles may be included in the cholesterol lowering program. 21462 [car, nut] Iatrogenic comes from the Greek word which essentially means an illness induced by a physician. This editorial focuses on iatrogenic illness with regards to neurology. In one study from Johns Hopkins Hospital in Baltimore, Maryland 1500 neurologic consultations were followed between 1978 and 1984. Iatrogenic neurologic complications were discovered in 14% of the patients. Previously unrecognized but significant neurologic complications were observed in 27% of these patients. The authors concluded from this data that the incidence of iatrogenic illness has been underestimated. Certain surveillance techniques have been shown to reduce iatrogenic complications. Increased utilization of adverse drug effect and drug-drug interaction data bases in outpatient settings have been beneficial. Health outcome data with improved feedback mechanisms to educate health care providers should help reduce the number of ineffective surgeries and medical treatments. Over the last 30 years research has indicated that at least 5% of hospitalizations result from some adverse consequence of physician- initiated treatment. Half of these are probably preventable. In prospective studies, the incidence of iatrogenic complications in hospitalized patients has ranged from 20 to 40%. Approximately half of such problems appear from adverse drug reactions. The author of this editorial states that neurosurgeons and neurologists need to become more aware of the risks for treatments and procedures that they utilize and perform. Since there is a high incidence of iatrogenic complications with neurologic symptoms or signs, neurologists can play an important role in making the medical community aware of this problem and its prevention. 21478 [med, neu] This study evaluated 351 white male with cases of bladder cancer compared to 855 controls for dietary factors. There was an increased risk of bladder cancer associated with higher calorie intake, but only among those under the age of 65. There was a positive association of risk with fat intake and a decreasing with higher protein intake. Carotenoid consumption appeared to decrease risk with increased consumption of those under age 65. There was no association for other nutrients noted. A higher intake of sodium was associated with an increased risk among both age groups. 21815 [can] This study evaluated 74 boxers who received bromelain 2 tablets given 4 times a day for 4 days or until signs of bruising had disappeared compared to 72 who received a placebo. All signs of bruising cleared completely in 4 days in 58 of the supplemented boxers and the remainder cleared in 8 to 10 days. Among the 72 controls at the end of 4 days only 10 had completely cleared. The remainder took 7 to 14 days to completely clear. 22096 [tra, inf] This study evaluated 76 patients during lumbar disc surgery for the calcium/magnesium ratio in the fibrous connective tissue from the ligamenta flava. The calcium/magnesium ratio was almost constant through all age groups. It was concluded that the constancy of the calcium/magnesium ratio throughout the lifetime is an integral quality of elastic fibers which may be explained by the long biological half-life of elastin. Magnesium plays a crucial role in connective fibers with elastic properties. Comparing elastic tissues with non-elastic tissues, with increasing elasticity, a magnesium/calcium ratio in favor of magnesium was found. The calcium/magnesium ratio was almost the same in patients with lumbar disc prolapse and with autoptic material from patients without herniated disks. Disk herniation through sclerotic or even ossified annulus fibrosus may be perceived as extreme aging of collagen. The biological half-life of uninjured elastin, the essential component of elastic fibers of ligamenta flava, is close to the lifetime of man. The authors conclude that the unexpected finding of a virtually unchanged calcium/magnesium ratio in ligamenta flava may be explained by the special biological behavior of elastin. 21785 [neu, ort] Participants in this survey included 3,115 residents and 1,920 practicing physicians in pediatrics, obstetrics/gynecology, and family medicine. The overall response rate was 68%. Less than 50% of the residents chose appropriate clinical management for a breast-fed jaundiced infant or a breast abscess. Practicing physicians performed slightly better, but still more than 30% chose incorrect advice for mothers with low milk supply. Most of the breast feeding instruction given by residents was from didactic lecture, not patient experience. Only 55% of senior residents recalled even one incidence of precepting related to breast-feeding, and less than 20% had shown breast-feeding techniques at least five times during their residency. More than 50% of all practicing physicians rated their residency training on breast-feeding counseling as inadequate. Physician involvement in breast feeding promotion was endorsed by 90% of the respondents, yet only half rated themselves as effective in counseling breast-feeding patients. The authors concluded that in this review of residents and practicing physicians in three specialties, physicians were ill-prepared to counsel breast- feeding mothers. 21780 [gyn, nut, ped] This study evaluated the relationship between insulin and weight gain in a prospective study in 97 Pima Indians with normal glucose tolerance. During a mean follow-up period of more than 3 years the average weight increased 2.1% per year in males and 3.5% per year in females. This reflects an annual increase in body fat content of 6.9% per year in both sexes. Insulin secretion was negatively associated with the rate of weight gain. The significance of the relationship between each measure of insulin secretion and weight gain persisted after controlling for variables. Slightly reduced insulin secretion is a significant and independent predictor of the tendency to gain weigh and adiposity in Pima Indians. The presence of relative insulin resistance also conferred an independent reduction in the risk of weight gain in some regression analysis. The authors conclude that insulin resistance and hyperinsulinemia are unlikely to play a causal role in the development of obesity. Relatively reduced insulin secretion is a marker of an increased risk of weight gain in this population. This data supports the hypothesis that the level of insulin secretion plays an important role in long term weight regulation. Relatively reduced insulin secretion contributes to the progression of both obesity and glucose intolerance in subjects who bear the thrifty "genotype", which progresses to overt B-cell failure and non insulin dependent diabetes mellitus. 22685 [end] Rationale for consuming fruits and vegetables is that they are a major dietary source of antioxidants. These natural antioxidants appear to protect DNA from cancer causing damage by free radicals. Clinical tests have shown little benefit from beta-carotene, vitamin E, vitamin C and the prevention of cancer. Clinical data has greater support for the use of supplemental antioxidants in the prevention of cardiovascular disease by protecting LDL cholesterol from oxidation and by reducing platelet aggregation. LDL cholesterol lowering agents include limonene, menthol, geraniol, perillyl alcohol, beta ionone, the carotenoids and tocotrienols. These substances also suppress tumor growth. Animals receiving one of the isoprenoids have markedly reduced levels of the enzyme HMGR and the animal's capacity to synthesize cholesterol is limited. These isoprenoids (tocotrienols, terpenoids) are most effective with low cholesterol diets which end up stimulating endogenous cholesterol synthesis. A variety of isoprenoids effectively suppress the growth of tumors in culture. It is proposed that minor isoprenoid constituents of fruits and vegetables suppress tumor growth by limiting the rate of synthesis of prenyl-PPs without bringing into play the side effects of high dose lovastatin. Other approaches to the control of hypercholesterolemia, the use of bile sequestrants, induce HMGR activity and at the same time promote tumor growth. In review, minor isoprenoid constituents of fruits and vegetables suppress hepatic HMGR activity as a rate limiting enzyme for cholesterol synthesis. These isoprenoids also suppress the synthesis of prenyl-PPs required for tumor growth. This data suggests that isoprenoids, which are agents in plant foods, play a role in the prevention of cardiovascular disease and cancer. 22684 [cho, can] This study evaluated sedentary adults which included 69 women and 66 men mean age of 50.6 years. They were either assigned to a control group, a moderate intensity walking group, low intensity walking group, low intensity walking plus relaxation group or a mindful exercise group - a Tai Chi program. Women in the Tai Chi group experienced reductions in mood measurements and improvement in general mood. Women in the walking group noted greater satisfaction with physical attributes and men in the walking group reported increased positive affect. No other differences were observed. The authors state there is equivocal support for the hypothesis that exercise plus positive strategy training are more effective than exercise programs lacking a structured cognitive component in promoting positive psychological benefits. 22847 [exe, psy] This study evaluated 11 healthy men between 21 and 32 years of age during a 90 day metabolic suite study. Daily copper intake for the first 24 days, the next 42 days and the last 24 days of the study was .66, .38 and 2.49 respectively. Feeding the diet with .38 mg of Cu per day was associated with a significant decrease in proliferation of peripheral blood mononuclear cells cultured in a variety of antigens and an increase in the percentage of circulating B cells. There was no effect on the concentration of serum interleukin II receptor, percentage of peripheral monocytes, neutrophils and T cell subsets or neutrophil phagocytic activity. When feeding 2.49 mg of copper per day for 24 days prevented decreases in indexes affected by the low copper diet it did not restore them to their prestudy levels even though plasma copper and ceruloplasmin concentrations were restored to normal. It is possible that other dietary or known dietary factors cause these changes. It is possible that the duration of the high copper intake of 2.49 mg per day for 24 days was not enough to reverse the effects of the low copper intake. Further studies feeding this amount for longer periods than 24 days and/or feeding amounts greater than 2.49 mg of copper per day are needed to clarify the effects of dietary copper on human immune response. 22975 [imm] This article describes a 2-component prevention strategy to waterborne illness. The strategy allows an individual to disinfect drinking water immediately after collection, and then store the water in a narrow-mouthed, closed vessel designed to prevent recontamination. New disinfectant generators and better storage vessel designs make this strategy practical and inexpensive. This approach enables households and communities that lack potable water to protect themselves against waterborne pathogens and has potential to decrease the incidence of waterborne diarrheal diseases. 21999 [env, inf] This study evaluated iron stores in 847 men and women between 40 and 79 years of age. Ferritin emerged as a strong indicator of carotid artery disease in both sexes between 40 and 59 years with an odds ratio of 1.54 per 100 ug/l. The predictive value of ferritin was found to be synergistic with that of hypercholesterolemia. Variations in body iron stores between the sexes may partly explain the sex difference in the expression of carotid atherosclerosis. In those greater than 60 years of age the predictive significance of ferritin was found to decrease parallel to that of apolipoprotein B. This current data suggests a role for body iron in early atherogenesis. 21894 [car] This study evaluated 252 patients with suspected, acute, myocardial infarction in a double-blind and randomized fashion who received 50 mmol of magnesium sulfate infusion under 20 hours or a placebo. Myocardial infarction was confirmed in 117 patients and 59% of these patients had thrombolytic therapy at the same time. One hundred and ninety-four patients had Holter monitoring during the first day in the coronary care unit. An intention-to-treat analysis showed an increase in the long RR-intervals in the magnesium treated group and a tendency towards a reduction in episodes of ventricular, premature, complex triplets. During the hospital stay and through a mean 22 month follow-up, 23 fatal events occurred in the magnesium treated group and 31 fatal events occurred in the placebo group. Mortality rate from cardiac disease was reduced by 54%. A subgroup analysis in acute myocardial infarction patients showed a 48% reduction in mortality risk in the magnesium treated acute myocardial infarction patients compared to the placebo treated patients. There was no significant interaction between the magnesium and the thrombolytic treatment on total mortality or cardiac events. This data is not in accordance with the recent large, ISIS-4 study conclusions but it does support other smaller, double-blind, placebo-controlled studies regarding the effects of magnesium on mortality in acute myocardial infarction. The authors are not clear on why there is this discrepancy between the large ISIS-4 study. It is possible that the antiplatelet effects of magnesium could explain the beneficial effect that magnesium therapy has in early conducted studies, and this effect is later diluted by a combination of thrombolytic and aspirin treatment. There may have been more low risk patients included in the ISIS-4 study. There was also a greater time delay of the open magnesium treatment in the ISIS-4 study which could inhibit the presumed counteracting magnesium effect on intracellular calcium-overload in acute myocardial infarction. It has been shown that magnesium protects the heart from ischemia- reperfusion injury. In the ISIS-4 92% of the randomized patients had acute myocardial infarction confirmed and the time from onset of the symptoms to randomization was a median of 8 hours. In this study 46% of the included patients had an acute myocardial infarction and the median symptom duration for these patients to randomization was 4 hours. The corresponding time in the LIMIT-2 for all randomized patients was a median of 3 hours. In the ISIS-4 the protocol recommended that thrombolytic therapy be given and the lytic phase completed before trial randomization. The likelihood of reperfusion occurring during magnesium treatment in the ISIS-4 study was therefore very low. The authors note that the study design in the ISIS-4 differed significantly from this study and others in the course of magnesium administration. 22478 [car] This is a case report of a 50-year-old steroid dependent, chronic obstructive pulmonary disease patient who had jejunoileal bypass in 1975 for the treatment of obesity. The patient developed ataxia, slurred speech and weakness for 2 days. The patient had 14-days of oral Doxycycline that was given for bacterial bronchitis. Four days later the patient presented similar symptoms 5 hours after ingesting a large pasta meal. No new antibiotics were prescribed. He was discharged on a lactose-free, low carbohydrate diet. Two months later the patient was hospitalized electively to produce D- lactic acidosis syndrome with oral carbohydrates. He received 4,000 Kcal/d in divided meals with 64% carbohydrate, 70% protein and 17% fat. This 60 hour challenge did not reproduce the syndrome. Two months later, the patient presented confusion, slurred speech, anxiety, weakness, ataxia, liquid diarrhea and a high anion gap metabolic acidosis after 3 days of trimethoprim- sulfamethoxazole therapy which had been given to him for a respiratory infection. He had not consumed dairy products or a high carbohydrate diet recently. When the antibiotics were stopped as well as the feedings there was total improvement by the next day. Three months later he tolerated 2 weeks of oral ciprofloxacin from another respiratory infection without development of symptoms. Several weeks later he had another respiratory infection and received trimethoprim-sulfamethoxazole. Three days after the first dose he developed dysarthria which resolved itself after stopping the antibiotic. The patient had developed several episodes of D- lactic acidosis after the antibiotics. Stool cultures yielded lactobacillus acidophilus resistant to the antibiotics. The authors note that oral antibiotics may induce D-lactic acidosis in patients with short bowel syndrome by promoting the overgrowth of resistant D-lactate producing organisms. Interactions between carbohydrate intake and antibiotic use are likely determinates of the development of this syndrome. The periodic use of stool cultures with antimicrobial susceptibility testing may be beneficial in optimizing the selection of the antibiotic therapies. The cautious use of antibiotics in patients with short bowel syndrome along with carbohydrate restriction and avoidance of lactobacillus-containing preparations seems justified. 22568 [gas] This is a review article on the role of behavior monitoring and intervention and the secondary prevention of ischemic heart disease. Studies show that anger, depression and anxiety are major factors in the development of ischemic heart disease. Anger is a strong predictor in the development of ischemic heart disease. The resistance to utilizing behavioral modification is not necessarily based on science as much as the resistance is largely due to paradigmatic scotomata, which is conceptual difficulties for those individuals who are not familiar with biopsychosocial research. Routine evaluation of ischemic heart disease patients with psychometric assessment may provide a cost effective way of getting cardiologists and internists to recognize the elevated levels of emotional stress in their patients. It is rare that cardiologists read psychosomatic journals. An alternative is publishing articles relating to behavior and cardiovascular disease in peer review cardiology-type journals. 21539 [car] This article reviews the role of the primary care physician in reducing polypharmacy in nursing home patients. The goal is to reduce the drug list of those drugs that are most likely to improve or maintain function. Anticonvulsants and antiarrhythmics can often be withdrawn and medications for angina and hypertension can be simplified. Those drugs are used solely for prevention such as lipid lowering agents or anticoagulants may not have a favorable impact on patients with limited life expectancies. The medication list should be reviewed carefully. There is 1.6 million patients in 20,000 nursing homes in the United States. The average age of the nursing home patient is 78 years old and they take 6 to 8 prescription medications. Drug interactions and side effects are common in the elderly. 22391 [ger, pha] In a severely iodine-deficient area, this study evaluated several hundred children from birth to 3 years of age for neurologic development. The prevalence of moderate and severe neurologic abnormalities among the 120 infants whose mothers received iodine in the first or 2nd trimester was 2% as compared to 9% among the 752 infants who received iodine during the third trimester or after birth. The prevalence of microcephaly decreased from 27% in the untreated children to 11% in the treated children. The mean developmental quotient at 2 years of age increased. Treatment in the third trimester of pregnancy or after delivery did not improve neurologic status but head growth and developmental quotients improved slightly. This research shows that up to the end of the second trimester iodine treatment protects the fetal brain from effects of iodine deficiency. Treatment later in pregnancy or after delivery may improve brain growth and developmental achievements slightly though neurologic improvement does not occur. 21549 [end, nut] This article reviews a variety of problems that occur in adolescents which include, iron deficiency, obesity, the eating disorders anorexia nervosa, and bulimia nervosa. This article also reviews the Food Guide Pyramid. Rapidly growing adolescents are at high risk for inadequate zinc levels, especially if they limit their intake of flesh foods and dairy products. Pregnant teenagers are specifically susceptible to zinc deficiency due to rapid cell division and growth of the developing fetus and continued personal growth. Pregnant adolescent vegetarians are at risk for calcium, iron, zinc, vitamin B12, and vitamin D deficiency. Adolescents who are capable of getting pregnant should take at least .4 mg of folic acid per day but no more than 1 mg per day. Smoking should be discouraged. 22830 [nut] This study evaluated photodynamic therapy in 123 patients with esophageal cancer. One hundred-four had squamous cell carcinoma and 19 had adenocarcinoma. A hematoporphyrin derivative was injected 72 hours before laser irradiation with a 630-nm dye laser. Photodynamic therapy was used solely in 56 patients and as part of a multimodal approach in 67 other patients. The 6 month response rate was 87%. The 5-year survival rate was 25%, and the 5-year disease-specific survival rate was 74%. The complete response rate and survival rate were not different between the group that received photodynamic therapy alone and the group that received photodynamic therapy plus the other modalities. There was no difference between the adenocarcinoma and the squamous cell carcinoma groups and those at different stages of cancer. Some of the side-effects of photodynamic therapy included esophageal stenosis, which occurred in 43 patients, and cutaneous photosensitization, which occurred in 16. The authors conclude that in patients who have a high surgical risk, photodynamic therapy is an effective treatment for a small esophageal tumor. 21744 [can] Eighteen adults with significant atopic dermatitis resistant disease that was nonresponsive to conventional therapy were treated with hypnotherapy with significant benefit both measured subjectively and objectively which was maintained for up to 2 years. Twenty children with severe resistant atopic dermatitis were treated with hypnosis and all but 1 showed immediate improvement which was maintained at the 2 following clinic appointments. In 12 children who completed follow-up questionnaires up to 18 months after treatment 10 showed that they had maintained the improvement in the itching and scratching, 9 in sleep disturbances and 7 maintained improvement in mood. The hypnotherapy program appeared to be economical for both time and money as there were 3 or 4 20 minute sessions of hypnotherapy which produced the long term benefit. This therapy is also free from any harmful side effects such as systemic steroids, PUVA or cyclosporin. It is valuable for children to learn these techniques early in the course of their chronic relapsing condition. 22482 [der] This article reviews the metabolic effects of dioxin-type chemicals in pesticides and other xenobiotics. The most consistent toxic effects of dioxin-type chemicals are hyperlipidemia, body weight loss, anorexia, changes in carbohydrate metabolism and lipid peroxidation. Dioxin-type chemicals affect lipoprotein lipases, low-density lipoprotein receptors, glucose transporter proteins, vitamin C uptake and insulin secretion. It is suggested that 2,3, 7,8-tetrachlorodibenzo-p-dioxin (TCDD) directly acts with isolated cytosolic aryl-hydrocarbon (Ah) receptor under cell-free conditions even without the presence of the nucleus and is capable of activating key protein kinases that are involved in the growth factor signal-transduction pathway. The resulting activation of the primary-response transcription factors in the nucleus appears to play a role in coordinating vital cell program shifts which include lipid metabolism. 21944 [env, nut] This study in a randomized, placebo-controlled, crossover trial gave nightly doses of oral DHEA at 50 mg to 13 men and 17 women between 40 and 70 years of age over a 6 month period. DHEA and DHEA sulfate serum levels were restored to those found in young adults within 2 weeks of the DHEA replacement and were sustained throughout the 3 months of the study. There was a two-fold increase in serum levels of androgens (androstenedione, testosterone and dehydrotestosterone) in women with only a small rise in androstenedione in men. There was no change in circulating levels of sex hormone binding globulin, estrone, or estradiol in either gender. High density lipoprotein levels declined slightly in females with no other lipid changes. Insulin-like growth factor-1 increased significantly, and insulin growth factor binding protein-1 decreased significantly for both genders. This was associated with a remarkable increase in physical and psychological well being for the majority of men and women with no change in libido. 22505 [end, ger] Genuine food intolerance can be due to a variety of mechanisms which include enzyme deficiency, pharmacological reaction, a toxic effect or, an immunologic reaction would be more specifically classified as a food allergy. The relationship to food and behavior is a noteworthy topic among the news media. Foods can have pharmacological effects. Caffeine for example in coffee and other foods can increase wakefulness and concentration but can also cause irritability. The peptides in milk and wheat have exorphin-like activity. Amino acids such as tryptophan in foods are the precursor to vaso-active mediators such as serotonin and can act as precursors for neurotransmitters. Food containing high concentrations of these amino acids may affect behavior, mood and appetite. Foods high in certain additives such as tartrazine have been shown to effect basophil's histamine release. It is not surprising that a high food additive- containing diet might accentuate hyperactive behavior by direct pharmacologic mechanism. The standard for diagnosis of food intolerance is the double-blind food challenge. Few clinics have the experience or the time to devote to this "painstaking" diagnostic procedure. In 1 study of 104 patients with severe migraines 38% improvement on diet, 26 reacted on open challenge with food but only 15% had reproducible symptoms on double-blind challenge. In 1 study 59 of 78 children referred to a diet clinic with hyperactive behavior improved on a few food diet, 19 subsequently had a double-blind challenge with the offending foods and a crossover challenge and clear differences were seen in 14 children with significant difference between active and placebo challenges. Whether total exclusion of a food is necessary or whether only a reduction of the pharmacologically active ingredients to reduce the reaction to food and improve behavior is not known. It is also important to note that in behavior problems in children it is natural for a parent to be lead to the believe that a particular symptom is due to a food which is an extrinsic factor versus some other psychosocial reason. The author concludes by this quote: "There is an association between certain foods and hyperkinetic disorders, but only in the minority of affected children". Still much work is needed to define the association between behavior, food and dietary modification. Individuals with genuine food-associated behavior should be evaluated to identify the underlying pathophysiological mechanisms which might improve the diagnosis and management of this in the future. 22932 [all, psy] This study evaluated serum aluminum levels in 356 healthy people. The authors observed that serum aluminum concentration is increased in aging people, in relation to age. It is possible that this is due to enhanced gastric permeability or by an increase in metal accumulation proportional to age. In measuring serum aluminum levels in patients with Alzheimer's disease, patients with other dementias and age-matched controls, researchers found that those with probable Alzheimer's disease have statistically significant higher aluminum levels than the patients with other types of dementias, including alcoholic, vascular and multi-infart, and the controls. When comparing the aluminum levels of patients with senile dementias from other causes with age-matched controls, there is not a significant difference. The authors conclude that human exposure to aluminum should be limited in aging individuals because of the physiologic accumulation of metal during their lifetimes. 22035 [env, neu, tox] This study evaluated the relationship between plasma cortisol, alcohol consumption and smoking with blood pressure in 297 Japanese men between 50 and 54 years of age. Plasma level of cortisol was positively related to systolic and diastolic blood pressure but cortisol levels did not vary substantially with alcohol consumption. Both blood pressure and plasma cortisol levels were lower among current smokers than nonsmokers. The lower blood pressure observed among current smokers is ascribed in part to the plasma cortisol levels. Cortisol levels may contribute to lower blood pressure among current smokers but the data does not support its role in mediating the alcohol-blood pressure relationship. 21907 [car] This article reviews the suggestion that cancer may be reduced by antioxidants found in fruits and vegetables. The author concludes, in this extensive review, that even though eating fruits and vegetables appears to reduce the risk of getting cancer, the role of antioxidants in the protection of cancer is still unproven. Antioxidant nutrients reviewed include beta- carotene, vitamin C, E, selenium and zinc. 22003 [can] This article reviews the chemistry and action of thioctic (à- lipoic) acid which is a drug used for the treatment of diabetic polyneuropathy in Germany. It is believed that thioctic acid acts as an antioxidant and interferes with the pathogenesis of diabetic neuropathy. These authors found that thioctic acid had a prolonged dose-dependent inhibitory effect on CU2+-catalyzed ascorbic acid oxidation and also increased the partition of copper into N-octanol from an aqueous solution suggesting that thioctic acid forms a lipophilic complex with CU2+. Thioctic acid also inhibited CU2+ catalyzed liposomal peroxidation. Thioctic acid inhibited intracellular H202 production in erythrocytes challenged with vitamin C. This study suggests that thioctic acid may work not only by reducing thioctic acid to dihydrolipoic acid may also operate via CU2+-chelation. 22859 [met] Ten cirrhotic patients, between 48 and 65 years of age, were evaluated over a 2 month period while taking S-adenosylmethionine (SAMe) at 800 mg per day. There was no significant change found in the percent composition of biliary amino acids except for an increase in glutamic acid and taurine. There was a trend towards increased percent tauroconjugation of all individual bile acids. There was a significant increase in taurochenodeoxycholic acid and a drop in glycocholic acid. In the cirrhotic liver exogenous S-adenosylmethionine is partially metabolized to taurine which is used for a bile salt. The authors conclude that giving S- adenosylmethionine to cirrhotic patients enhances bile salt tauroconjugation. 21524 [gas] In a mouse model UVB radiation was evaluated on mice skin that had been covered topically with vitamin E acetate 5% in a clear thick oil at room temperature. The concentration applied was approximately 5 mg/cm2. Topical application of vitamin E acetate results in an increase in the concentration of free tocopherol in the skin. There were no qualitative differences in the ultrastructural appearance of the UVB irradiated, tocopherol acetate treated skin on careful examination. In vivo microscopy of blood flow in the venules of irradiated mouse ear revealed a large but not statistically significant decrease in stationary lymphocytes adhering to the venule walls. The delaying of the application of vitamin E acetate up to 8 hours after the ending of the UVB irradiation still offered statistically significant protection as did immediate application of the 5% vitamin E acetate in diluent Myritol 318. 22599 [can, der] This is a review article on the role of vitamin C and fertility. Vitamin C has long been associated with fertility. Vitamin C may benefit fertility through its ability to promote collagen synthesis, its role in hormone production and its ability protect cells from free radicals. Vitamin C accumulates in tissues of the ovary and testis. Both of these tissues have cycles of remodeling and of peptide and steroid secretion which appear to be vitamin C dependent. Vitamin C may prevent these cells from free radical damage during production and fertilization. Data suggests that the supply of vitamin C to the ovary might be a limiting factor in the ability of the preovulatory follicle to grow in response to gonadotropin stimulation. Because of the gene mutation, primates, guinea pigs and bats lack one of the liver enzymes important in the biosynthesis of vitamin C, L-gulono-lactone oxidase. Therefore these animals, including man, require a dietary supply of vitamin C. Tissue content of vitamin C varies, but the highest concentrations occur in the pituitary, adrenal gland, and in gonads. Leukocytes, particularly neutrophils, have very high concentrations of vitamin C, and are probably the primary vehicles for its distribution in the body. Vitamin C is an electron donor and is an essential co-factor for enzymes that hydroxylate proline and lysine residues during the post-transitional processing of pro- collagen. In the absence of vitamin C the pro-collagen is unable to assume its trihelical conformation and cannot be secreted by the cell. Ascorbate is reported to promote collagen production at the gene level. The synthesis of the hormones oxytocin, vasopressin and catecholamine . . . and steroidogenesis . . . all appear to be ascorbate-dependent. The antioxidant properties of vitamin C help protect DNA, proteins, carbohydrates, lipids and biological membranes from free radicals. Low or deficient vitamin C levels have been associated with low sperm count, increased numbers of abnormal sperm, reduced motility, and agglutination. The beneficial effects of vitamin C on sperm may be the destruction of free radicals present as a consequence of environmental pollution and cellular metabolism, which would otherwise cause oxidative damage to DNA. The ovary has long been recognized as a site of ascorbic acid accumulation and turnover. There is a change in the retention and excretion of vitamin C at mid-cycle in women, associated with luteinizing hormone secretion and temperature rise, which has been proposed as a definite marker of ovulation. It appears that vitamin C excretion increases in the late follicular phase, declines immediately prior to ovulation, and increases again immediately after the rise in body temperature. It has been suggested that the retention before ovulation enhances luteal steroidogenesis. Ascorbate appears to be stimulatory to progesterone and oxytocin secretion. The concentration of vitamin C in the corpus luteum appears to be in significant excess of that which is required to facilitate hormone production. An explanation for vitamin C's abundance in the ovary is the high rate of tissue remodeling and collagen synthesis during the follicular-luteal cycle. Collagen synthesis is required for follicular-luteal growth, for repair of the ovulated follicle, and for corpus luteum development. Vitamin C is also needed for secretion of collagen and proteoglycans into follicular fluid. As with males, vitamin C has been suggested as a regulator of female fertility. Vitamin C supplementation enhances the ovulation-inducing effects of clomiphene by an apparently local ovarian effect. Large quantities of vitamin C are utilized during human conception and are necessary to maintain the integrity of fetal membranes. Dietary supplementation during pregnancy may reduce the frequency of birth defects, and a daily supplement of at least 500 mg of vitamin C, starting as early in pregnancy as possible, has been suggested for pregnant mothers. None of these proposals have been translated into clinical practice. The available human data suggests that a re-examination of the clinical potential of vitamin C would be appropriate and timely. 21764 [rep] It is noted that people in Japan smoke more cigarettes than those in western countries, yet their incidence of lung cancer is lower. This has been attributed in part to the high tea consumption in Japan. At the same time laboratory data shows a preventive effect of tea in models of lung cancer. The antioxidant potential of tea lowers the modification of DNA in the lung by hydroxyl radicals or similar active oxygen compounds. John H. Weisburger, Ph.D. who heads the chemoprevention research on tea at The American Health Foundation recommends drinking 4 to 5 cups of tea daily. In mice models, drinking green tea resulted in lung tumor induction being inhibited by 50%. Tea has potent antioxidant power. Green and black tea reduce the incidence of cancer of the lung, forestomach, esophagus, and liver in rats and mice when these were induced by carcinogens. In another rat model, green tea consumption lowered tumor incidence over controls receiving water. Other studies show a lower incidence of colonic polyps in humans drinking green tea. Tea and tea polyphenols may inhibit the initiating events caused by diverse carcinogens through several possible mechanisms. Green and black tea and associated polyphenols decrease the genotoxicity of heterocyclic amines in model systems. Solutions of black tea and green tea and the polyphenols theaflavine gallate from black tea and epigalocarechin gallate from green tea have equivalent inhibiting actions on the mutagenicity of heterocyclic amines in the Ames and Williams Test. The underlying mechanism appears to involve the cytochrome P450 system, and phase II conjugating, detoxifying enzymes. Glucuronyl transferase was similarly increased by green and black tea which suggests that the tea may reduce carcinogenesis by raising the level of detoxifying enzymes. Through mechanisms that remain to be defined, tea stabilizes gap junctions and diminishes the activity of promoters. Tea also has antiviral effects. The powerful antioxidant potential of epigalocarechin and related catechins in green tea, and the theaflavines and thearubins in black tea, may account for the lowered risk of atherosclerosis and coronary heart disease in tea drinkers. The polyphenols in tea have multiple effects influencing the risks for diverse types of cancer. Individuals drinking 4 or more cups of tea per day gain a benefit equivalent to that derived from eating 2 of the recommended 5 to 9 servings of fruits and vegetables daily. Tea consumption is a complement to a healthy lifestyle, which should include avoidance of tobacco use, eating a low-fat and low-salt diet, increasing fiber intake, and exercising regularly. 21917 [can] The increase in Crohn's disease that has taken place over the last 50 years is parallel to the increasing use of antibiotics in human and veterinary medicine. Insufficient doses of antibiotics can induce the capacity for toxin production in bacteria or can make them invasive. Prior antibiotic therapy also promotes the outbreak of Crohn's disease to a statistically demonstrable extent. It may be assumed that Crohn's disease is caused in genetically susceptible persons by intestinal bacteria whose biological but not morphological properties have been altered by antibiotics. Mycobacterium paratuberculosis has been repeatedly suspected though not proven to be a bacterial cause of Crohn's disease. Crohn's disease improves in sections of the intestines that are operatively excluded from fecal flow. It deteriorates again when intestinal continuity is restored. An important finding is the connection between the administration of inadequate amounts of antibiotics and the resulting bacterial toxin production in intestinal organisms. It is also noted that it is not possible to induce colitis in germfree guinea pigs and rats by carrageenan or indomethacin. It is concluded that Crohn's disease, after 1950, spread like an epidemic initially in Northern Europe and the U.S.A., which suggests infectious disease. There appears to be a genetic component as well. The importance of environmental factors is indicated by the effects of migration. The epidemic-like spread of Crohn's disease over roughly the last 50 years started with the introduction of antibiotics and developed in parallel with an increase in antibiotic consumption. The authors hypothesize that Crohn's disease is an infectious disease. Its pathogen is a component of the morphologically normal flora, possibly a coliform bacterium, which suddenly produces immunostimulating toxins or becomes invasive. It has acquired its ability due to contact with nonkilling or insufficient amounts of antibiotics. Organisms toxified in this manner are transmissible. Statistics indicate that wherever antibiotics were used early and in large quantities and no genetic insensitivity is present, as in the United States, England, Scotland and Sweden, the prevalence of Crohn's disease is high. Population groups who for social or other reasons were initially less well supplied with antibiotics, such as persons living in third-world countries, show a delayed increase. Pretreatment with antibiotics for other diseases can encourage the development of Crohn's disease. 21967 [gas, inf] Over a 2 year period 12 asthmatic patients were presented to the Emergency Department with acute respiratory acidosis with a pH of less than 7.35 and Pa-C02 greater than or equal to 45 mmHg. All 12 patients were treated with Heliox which is 60 to 70% helium/30 to 40% oxygen. Five patients receive Heliox through a ventilator and 7 received Heliox via face mask. Sixty-seven percent were responders and 33% were nonresponders. The responders were defined as those having a drop in PaCO2 to normal or by greater than or equal to 15% coupled with a rise in pH by greater than or equal to .05%. The responders had a shorter duration of symptoms of 17.8 hours versus 7 to 8 hours and a lower pre Heliox pH of 7.20 versus 7.30. All other responders presented with 24 hours of symptom onset. Three of 4 of the nonresponders reported prolonged duration of symptoms and 2 eventually required intubation. The authors concluded that Heliox can rapidly improve ventilation in patients presenting to the Emergency Department with acute severe asthma and respiratory acidosis. 22797 [pul] This was a nationwide case-controlled study covering a region with 78% of all births in New Zealand between 1987 and 1990. Interviews were completed with the parents of 393 cases of infants who died with sudden infant death syndrome in the postneonatal age group and 1,592 controls. 26% of the SIDS deaths were explained by bed sharing among infants of smoking mothers and 3% by bed sharing among infants of nonsmoking mothers. The majority of SIDS deaths that are attributed to bed sharing occur among infants of smoking mothers. This data should not be interpreted to suggest that bed sharing where the mother is a nonsmoker is safe or protective against SIDS. The authors conclude that an extra 3% of sudden infant deaths could be saved by a general message for all infants not to bed share compared to messages targeted to the infants of smoking mothers. Current favorable attitudes towards infant bed sharing may jeopardize the acceptance of other cot death prevention messages if it is perceived that the evidence does not justify a general recommendation against this practice. 22675 [ped] This study evaluated the hypothesis that 3 weeks of oral lactate supplementation affects post exercise lactate disappearance in untrained athletes. Eight men received lactate supplementation which was a drink containing 10 gm of lactate which was of the following composition: 8.2 gm calcium lactate powder, 6.25 ml sodium lactate solution (60% lactate), 2.05 ml of potassium lactate solution (60% lactate), diluted to 100 ml with water. The mineral quantity ingested as a result of the lactate salts amounted to 1.5 gm calcium, 1 gm sodium and .5 gm potassium. The drink was given twice a day or a placebo was given in 7 patients which contained maltodextrin. The 3 week supplementation of oral lactate did not result in differences in lactate disappearance. This data does not support the hypothesis that regular oral lactate intake at rest enhances the removal of lactate during and following exercise. 22968 [exe] This study evaluated the relationship between plasma cortisol, alcohol consumption and smoking with blood pressure in 297 Japanese men between 50 and 54 years of age. Plasma level of cortisol was positively related to systolic and diastolic blood pressure but cortisol levels did not vary substantially with alcohol consumption. Both blood pressure and plasma cortisol levels were lower among current smokers than nonsmokers. The lower blood pressure observed among current smokers is ascribed in part to the plasma cortisol levels. Cortisol levels may contribute to lower blood pressure among current smokers but the data does not support its role in mediating the alcohol-blood pressure relationship. 21907 [car] People 65 years of age or older comprise 12% of the population. Those over 85 are the fastest growing segment of the population. This number of older individuals is expected to double to almost 65 million within the next 40 years. Aging can produce physiologic changes that affect the need for several essential nutrients. The most recent edition of the recommended daily allowances (1989) continues to give guidelines for assessing the intake of energy and specific nutrients for adults up to age 50 and for 51 years or above. The physiological features of health status of individuals who are 50 to 60 years of age are very different from those between 80 and 90. One of the issues is whether nutritional requirements should be adjusted on the basis of observed age-associated changes in body composition of physiologic function or whether optimal body composition levels of function should be determined for different age groups and nutrient intakes designed to achieve them. A related RDA issue is whether nutrient requirements should focus on adequate intakes necessary to maintain the existing health for any particular age group or whether nutrient intake should be associated with maximal reduction of disease risk. RDAs based on age alone may be misleading. The possible benefits to middle aged and older individuals of nutrient supplementation beyond the recommended daily allowances remain controversial. There is some evidence that suggests that dietary requirements for some nutrients to prevent deficiency and maintain apparent health in young adults may be considerably less than the optimal amounts necessary to provide protection against degenerative diseases. Some examples in the elderly include the metabolic demand for vitamin B6 to maintain glucose tolerance and normal cognitive function in older adults, which appears to be higher than previously assumed. Vitamins B6 and vitamin E can reverse some trends in immune function and actually enhance this function. Stomach acid secretion of hydrochloric acid reduces with age which may effect the ability to absorb vitamin B12. Elevated homocysteine is an independent risk factor for cardiovascular disease, depression and other neurocognitive functions and can be normalized with vitamin B6, B12 and folic acid status. With aging there is a reduced capacity to synthesize vitamin D from sunlight and a depression in the kidney's ability to convert vitamin D to its biologically active form. Those individuals with higher nutritional status of vitamin C, E and beta-carotene appear to have a reduced risk for cancer, cataracts and heart disease. Marginal zinc deficiency is common among the elderly and is associated with taste acuity, wound healing and mental function. Certain localized deficiencies of vitamins, such as folic acid with cervical dysplasia, vitamin E with fibrocystic breast disease, vitamin C with atrophic gastritis and beta-carotene with oral leukoplakia are also of concern in the elderly. Calcium intake at 1,000 to 1,500 mg per day could be an improvement over the 800 mg RDA for 1989. The RDAs are intended to be "neither minimal requirements nor necessarily optimal levels of intake". Formulation of optimal nutritional allowances that are pertinent to aging should include functional assessment of markers such as homocysteine. Elevated levels of homocysteine appear to be a risk factor for cognitive impairment and vascular disease and deficiencies of vitamins B6, B12 and folic acid. Many of the biological changes and risks to disease that have been attributed to aging are actually caused by suboptimal diet and nutrition. As Dr. Walter Bortz of Stanford University has said, "We live too short and die too long." Recognizing changes in nutrient requirements with age and the selection of nutrient-dense foods by older individuals may add significantly to the quality and functionability of their lives in later years. 21448 [ger, imm, nut] Ten women were evaluated during different stages of reproduction on calcium and bone metabolism. Fractional calcium absorption and concentration of 1,25-dihydroxyvitamin D were higher in the 2nd and 3rd trimesters. Total urinary calcium was higher during pregnancy and lower during the post weaning phases. Parathyroid hormone concentrations were higher only during post weaning. Serum tartrate resistant acid phosphatase and bone specific alkaline phosphatase and urinary deoxypyridinoline markers of bone turnover increased at the 3rd trimester and during lactation. Serum procollagen I carboxypeptides increased only in the 3rd trimester. Bone mineral density by single-photon absorptiometry did not differ during the different periods. The authors conclude that absorption in the urinary excretion of calcium increased during pregnancy whereas bone turnover increases during late pregnancy and lactation. 22371 [end] This study evaluated 22 preeclamptic women and 40 normotensive women for polyunsaturated fatty acid status. After adjusting for variables, women with the lowest level of omega-3 fatty acids were 7.6 times more likely to develop preeclampsia as compared to those women with the highest level of omega-3 fatty acids. A 15% increase in the ratio of omega-3 and omega-6 fatty acids was associated with a 46% reduction in risk of preeclampsia. Low levels of omega-3 fatty acids and high levels of omega-6 fatty acids, particularly arachidonic acid, appeared to be associated with an increased risk of preeclampsia. The data suggests that dietary consumption of omega-3 fatty acids, which is provided in fish oil, can alter eicosanoid metabolism which tends to favor vasodilation. The chemical roles of omega-3 fatty acids in reducing circulating triglycerides and decreasing platelet and leukocyte reactivity, as well as their ability to reduce blood pressure and increase utero placental perfusion, are consistent with this observation. 22650 [obs] Eight children with severe persistent anemia unresponsive to oral iron therapy were treated with intravenous iron saccharate. Hemoglobin rose from 8 g/dL to 11 g/dL. The concentration of serum transferrin receptor, an indicator of iron deficiency, before intravenous therapy, correlated with the increase in hemoglobin. The authors conclude that intravenous iron saccharate could be an effective treatment for chronic anemia in this condition, especially when the iron deficiency is not responsive to oral iron. 22050 [rhe] Bronchopulmonary dysplasia is a chronic lung disease that follows mechanical ventilation which necessitates supplemental oxygen beyond 1 month of age. It is clinically seen most frequently in premature births of 24 to 32 weeks gestation in infants whose breathing must be assisted mechanically. Mechanical ventilation causes pulmonary barotrauma and oxygen toxicity from chronic use of high concentrations of inspired oxygen. This results in stiffer, less compliant lungs and oxygen dependency. Difficulty in ventilating the infants produces chronic hypoxemia and hypercarbia. Undernutrition and poor linear growth are common findings in these infants. Insufficient energy intake reduces the ability to improve oxygenation and therefore slows respiratory muscle development to improve ventilatory effort. An interesting point is that all premature infants with bronchopulmonary dysplasia have functionally immature gastrointestinal tracts which may cause maldigestion. To meet this need, in some medical centers preterm milk is fortified to increase its energy, protein, and mineral content. Studies using fortified preterm human milk demonstrate normal growth in preterm infants, which is a growth that approximates the rate that is seen during the 3rd trimester of intrauterine life. Most premature infant formulas have a caloric density that is greater than that of preterm milk. Infants with bronchopulmonary dysplasia must have a formulation with a higher caloric density than other premature infants. Because energy deficits occur gradually, there must be constant and consistent monitoring of the infantþs energy needs, and an appropriate response in terms of the amount of formula delivered. Attention to this detail will provide the infant enough energy to prevail over the disease. 21477 [gas, ped, pul] This was a prospective study of 40 uremic non-responders to one complete hepatitis B vaccination cycle underwent a second hepatitis B vaccination. In 28 of these patients, zinc substitution was given which was 60 mg of zincaspartate given intravenously in a short infusion after each hemodialysis, which was 3 times per week for 4 months. This was 2 months before the vaccination and 2 months after. The chronic uremic patients showed subnormal predialysis plasma zinc concentrations compared to the healthy controls. In the zinc treated patients, plasma zinc concentrations increased and were maintained during the treatment. After the hepatitis vaccination, a seroconversion was seen of 5 of 28 zinc treated subjects and 2 of 12 controls. This was not a significant difference between the 2 groups. The authors conclude that the diminished response to hepatitis B vaccination in chronic uremic patients is refractory to zinc supplementation. 21798 [inf, nep] Air pollution, airborne allergens, and changing weather can affect physical activity. High ozone levels can cause restrictive lung dysfunction and high carbon monoxide levels can impair oxygen delivery. Sulfur dioxide worsens nasal symptoms in individuals with allergies and may cause bronchospasm in those who have asthma. Airway irritation from fine particles can lead to bronchospasm. Atopic individuals can have adverse effects to fungi and pollens. Medications may be needed if a change in exercise routine does not relieve the symptoms. People who live in cities that have long term average ambient irritant levels appeared to be at higher risk for respiratory symptoms. In those doing aerobic exercise near traffic carbon monoxide congestion can raise carboxyhemoglobin levels to those found in smokers. It may be beneficial to check the media for reports of allergen and pollution levels that can help those individuals who are sensitive, to avoid peak times of concentration for outdoor exercise. It is important to choose exercises that can be performed in warm, humid environments such as a pool; if one is working out in cold weather, wear a scarf or an industrial type disposal mask over the mouth to limit the exposure of cold air and pollutants; breathe through the nose whenever possible to warm and humidify inspired air; Work out inside when pollutants or allergen levels are high outside; do 5 to 10 minutes of stretching and breathing exercises before a high intensity workout; work out slowly for the first few minutes after a warm-up; do a 10 to 15 minute cool-down after a workout. 22799 [all, pul] This was a cross-sectional study evaluating 99 women, 44 of whom had silicone breast implants. The results of this study showed that silicon-specific T-cell responses were seen in twice as many symptomatic as asymptomatic women exposed to silicone breast implants. This suggests that cell-mediated immunity plays a role in the development of abnormal reactions associated with silicone. This may provide a new, specific screening test. 21661 [aut, rhe] It has been a hypothesis that sugars are a cause of excessive energy intake and obesity. Experimental studies provide evidence that an ingestion of 50 gm of sugar or more within 20 to 60 minutes of a meal resulted in reduced meal time food intake which suggests that appetite regulatory centers respond to sugar's energy content. Epidemiologic data suggests that sugar consumption, as well as carbohydrate consumption, is associated with leanness and not obesity. Studies on the effect of sugar energy and sweetness of food intake do not support the conclusion that sugars have an effect on food intake that is not simply predicted by their energy content. The hypothesis that sugar is unique among carbohydrates because it's hedonic properties override food-intake regulatory controls normally shown by carbohydrate foods remains unsupported. 22765 [nut] Menatetrenone or vitamin K2 at greater than 3 times 10-6 M significantly inhibited the calcium release from mouse calvaria induced by 3 x 10-10 M of 1,25(OH)2D3 or 10-7 M of prostaglandin E2. It also inhibited osteoclast-like multinucleated cell formation induced by 10-8 M of 1,25(OH)2D3 in coculture of spleen and stromal cells of the same concentrations. The same dose of vitamin K1 had no effect on bone resorption and multinucleated cell formation (MNC) in these in vitro systems. The inhibitory effect of vitamin K2 on the calcium release from calvaria was not affected by the addition of 3 times 10-5 M of warfarin, an inhibitor of vitamin K cycle. These results suggest that the inhibitory effect of menatetrenone (vitamin K2) on bone resorption is not due to gamma carboxylation and that the side chain of menatetrenone may play an important role in this inhibitory effect. 21881 [ort, mat] This study evaluated 3 gm of eicosapentaenoic acid in a double- blind, randomized, multi-center study that was given from 12 to 14 weeks of gestation onwards. Sixty-three subjects with a history of intrauterine growth retardation with or without pregnancy-induced hypertension in the previous pregnancy were evaluated. One-third of the women developed pregnancy-induced hypertension and þ of the infants had a birth weight below the 10th centile. There was no difference between the placebo and in the eicosapentaenoic acid group. This study suggests that 3 gm of eicosapentaenoic acid daily does not prevent the recurrence of intrauterine growth retardation or pregnancy induced-hypertension in a high risk population. Future studies should utilize higher doses of EPA preferably in combination with a diet low in arachidonic acid. 22189 [obs, ped] High intensity strength training may reduce a postmenopausal woman's risk for osteoporotic fracture. Such training is protective on bone mineral density and promotes increased muscle mass, strength, dynamic balance and overall activity levels in postmenopausal women. This is the first time that a single program has shown to affect so many different risk factors for osteoporosis. In this study women trained on pneumatic machines. However, a home-based strength training program, using inexpensive dumbbells or water filled milk containers, may also give benefit. The strengthening program is feasible for frail individuals; it may significantly improve strength, mobility and functional status without risk to subjects. In this study, 39 white, sedentary, postmenopausal women were randomized to an exercise training group and a control group. Women in the exercise group participated in high intensity strength training 2 days per week for a year. Pneumatic resistance machines were used; exercises included hip extensions, knee extensions, lateral pull-downs, back extensions and abdominal flexion. At the end of the study femoral neck bone mineral density and lumbar spine density in the strength-trained women had increased 1.0%. In the controls femoral neck bone mineral decreased by 2.5% and lumbar spine bone mineral density decreased by 1.8%. The total body mineral content was preserved in the strength trained women, but a decrease of 1.2% was seen among women in the control group. Total body muscle mass, muscle strength and dynamic balance increased in the strength trained women and decreased in the controls. Women who exercised increased their energy expenditure and activities exclusive of the intervention by 27%. Controls decreased their spontaneous activity by 25%. 21897 [ort] Rationale for consuming fruits and vegetables is that they are a major dietary source of antioxidants. These natural antioxidants appear to protect DNA from cancer causing damage by free radicals. Clinical tests have shown little benefit from beta-carotene, vitamin E, vitamin C and the prevention of cancer. Clinical data has greater support for the use of supplemental antioxidants in the prevention of cardiovascular disease by protecting LDL cholesterol from oxidation and by reducing platelet aggregation. LDL cholesterol lowering agents include limonene, menthol, geraniol, perillyl alcohol, beta ionone, the carotenoids and tocotrienols. These substances also suppress tumor growth. Animals receiving one of the isoprenoids have markedly reduced levels of the enzyme HMGR and the animal's capacity to synthesize cholesterol is limited. These isoprenoids (tocotrienols, terpenoids) are most effective with low cholesterol diets which end up stimulating endogenous cholesterol synthesis. A variety of isoprenoids effectively suppress the growth of tumors in culture. It is proposed that minor isoprenoid constituents of fruits and vegetables suppress tumor growth by limiting the rate of synthesis of prenyl-PPs without bringing into play the side effects of high dose lovastatin. Other approaches to the control of hypercholesterolemia, the use of bile sequestrants, induce HMGR activity and at the same time promote tumor growth. In review, minor isoprenoid constituents of fruits and vegetables suppress hepatic HMGR activity as a rate limiting enzyme for cholesterol synthesis. These isoprenoids also suppress the synthesis of prenyl-PPs required for tumor growth. This data suggests that isoprenoids, which are agents in plant foods, play a role in the prevention of cardiovascular disease and cancer. 22684 [cho, can] This article reviews the role of nutrition on gastrointestinal barrier function, especially in the intensive care unit. It is noted that the conditions in the intensive care unit can result in dysregulation of the epithelial barrier. This may lead to absorption of autotoxic macromolecules that are very large and diverse that normally stay in the gut lumen. This may cause significant immunologic problems. It may be that alterations in the intestinal microecology from such intensive care therapies as antibiotics, artificial nutrition and antacids in conjunction with altered mucosal immunity from drug immunosuppression and artificial nutrition may contribute to the systemic inflammatory response syndrome. Because the gastrointestinal tract contains more neutrophils and macrophages than all other organs combined, bacteria that trigger local cytokine release may significantly influence the systemic inflammatory response. Simple attachment of the microbe to the mucosal cellular target can result in activation of a signal transduction pathway in epithelial cells that activate the inflammatory cascade. Nutrition's effect on very early events in this process, specifically mucosal immunity and bacterial adherence, may give valuable insights into the mechanism by which diet influences the systemic inflammatory response. Pharmacologic and neuroendocrine mimicry may be needed for future nutritional formulations for the critically ill patient to reproduce the same immune responses that occur after eating normal food. 21605 [gas, imm] This study evaluated 97 postmenopausal women who were randomized to either a group that was provided with soy foods for 4 weeks or a control group that instructed to eat as usual. The percentage of vaginal superficial cells increased in 19% of those eating the diet compared with 8% of the controls. FSH and LH did not decrease significantly with dietary supplementation as hypothesized, nor did sex hormone binding globulin increase. There was little change in endogenous estradiol concentration or body weight during the diet. Women with large increases in urinary isoflavone concentrations were not more likely to show an estrogenic response than were women with more modest increases. On the basis of published estimates of phytoestrogen potency, a 4 week soy supplemented diet was expected to have an estrogenic effect on liver and pituitary in postmenopausal women, but the estrogenic effect was not seen. At most, there was a small estrogenic effect on vaginal cytology. 22678 [end] This study evaluated 9 nonsmoking men between 23 and 37 years of age regarding the association between exercise intensity and related oxidative stress. The subjects exercised 30 minutes at their aerobic and anaerobic thresholds. The researchers also tested the effect of oral N-acetylcysteine on exercise-associated rapid glutathione oxidation in the subjects performing 2 identical maximal bicycle ergometer exercise tests. Before the second test, the men took 200 mg 4 times per day of N-acetylcysteine tablets for 2 days and an additional 800 mg on the test morning. Blood samples were drawn before, immediately after and 24 hours after the tests. Total and oxidized glutathione levels in the blood were determined. Though there was an association between a single bout of exercise and leukocyte DNA damage, the study suggested that the parameters may not serve as a sensitive index to assess the role of exercise intensity and the extent of exercise-associated oxidative stress. Plasma thiobarbituric acid reactive substances did not change after the maximal bicycle ergometer exercise test or the same exercise test with N-acetylcysteine supplementation. N-acetylcysteine supplementation resulted in an increase in the pre-exercise net peroxyl radical scavenging capacity. Supplementation may have spared exercise-associated blood glutathione oxidation and thiol redox changes. N-acetylcysteine supplementation increased the net peroxyl scavenging capacity of the plasma, indicating that the antioxidant properties of the drug may enhance the net antioxidative capacity of the plasma. It is possible that exercise- associated changes of the blood glutathione redox status may be circumvented by supplementation with N-acetylcysteine. 22023 [exe, met] In a recent study from the University of Georgia published in the August 1994 issue of The Journal of Medicinal Chemistry there appears to be a link between nutrition and the life cycle of the AIDS virus. Selenium's function through its antioxidant activities has slowed the aging process of the body by preserving the quality of tissue. The HIV virus is hypothesized to deplete the body of its stores of selenium. Once the virus has exhausted selenium in the infected cell, the cell bursts and the virus replicates. The theory suggests that the HIV virus produces proteins that use up the body's selenium supply. Reduced selenium levels have been documented in AIDS patients. 21983 [aid, nut] This article reviews red and white wine and how particularly red wine may trigger a migraine headache. It could be that dietary migraine sufferers may already have a reduced detoxicating ability, which allows noxious phenols to enter the blood stream in sufficient concentrations to provoke a migraine attack. Ingestion of powerful inhibitors of phenolsulphotransferase such as that in red wine could facilitate this process. Red wine also is known to strongly inhibit the binding of 5 hydroxytryptophan to 5 hydroxytryptophan1 receptors. White wine possesses this ability to a lesser extent. This is preliminary work. Sumatriptan, which is a powerful antimigraine medication, is known to strongly act on these receptors. Adversely red wine has been shown to a selective MAO A inhibitor and white wine possess selective inhibition for human MAO B. 22896 [neu] In evaluating 4,400 Vietnam veterans it was found that impotence occurred at a 50% higher rate among current smokers than in nonsmokers or past smokers. The rate of impotence in nonsmokers was 2.2%, 2% for former smokers and 3.7% for current smokers. This work was reported in the American Journal of Epidemiology, 1994;140:1003-1008. 21625 [rep] This study evaluated the relationship of vaginal candidiasis and the potential reservoir from the gastrointestinal and rectal areas. Cultures for yeast were obtained from the mouth, rectum, vulva and vagina every 1 to 2 months for 1 year in these patients assessed. In 37 healthy controls 8.1% had yeast cultured from the vulva, vagina and rectum and 10.8% from the mouth. In 193 patients with vaginitis 98.4% had yeast cultured from the vagina, 55.4% from the vulva, 48.2% from the rectum and 26.9% from the mouth. During visits without vaginitis 10.1% had yeast cultured from the rectum, 11.6% from the vulva, 13.1% from the vagina and 15.2% from the mouth. Yeast in the lower bowel during symptomatic vaginitis is higher than in controls but not significantly greater during the asymptomatic period. Recurrence of candida vaginitis is not dependent on the yeast reservoir from the lower gastrointestinal tract between symptomatic episodes. These results suggest that the intestinal reservoir is not a likely source for the recurrence of vaginal candidiasis. Failure of oral nystatin or oral imidazole to prevent recurrences adds further proof to the findings that carriage of yeast in the lower gastrointestinal tract is probably not related to the pathogenesis of chronic, recurrent, vulvovaginitis. There may be mild cellular immunity impairment that is undetected. 21350 [gyn] This study evaluated 177 children with post-measles complications divided into 2 groups. Eighty-nine children received vitamin A in doses of 200,000 I.U. daily on 2 consecutive days in addition to antibacterials and other supportive care; 88 did not receive the vitamin A. The case fatality rate was 16% in those who received vitamin A while it was 32% in those who did not receive vitamin A. There was no statistical difference in the mortality rate among the 2 groups when the children were suffering from severe malnutrition or encephalopathy. There is considerable evidence that vitamin A deficiency occurs during measles. It is possible that the beneficial effect of vitamin A is mediated by an effect on epithelial cell maturation. Vitamin A did not show any beneficial effect in severely malnourished patients in this study. It is possible that there was a defect of utilization of vitamin A in these children. 21870 [inf] This study of Harvard University Alumni evaluated 17,321 men mean age of 46 years and found a graded inverse relationship between total physical activity and morbidity. Vigorous activities but not nonvigorous activities were associated with longevity. Among those men who reported vigorous activity there were 259 deaths and among those who reported nonvigorous activity there was 380 deaths. Physical activity can improve cardiac, mechanical and metabolic function, reduce platelet aggregation and increase fibrinolytic activity. Sedentary individuals should increase their activity level to enhance longevity. Specifically vigorous activities were associated with greater longevity. The authors do note that even nonvigorous exercise is preferable to sedentariness. These findings were only pertinent to all cause mortality. It is noted that modest exercise can improve lipid and glucose profiles. 22245 [exe, ger] This study evaluated 106 statements about drugs during 13 presentations by pharmaceutical representatives for accuracy per the 1993 Physician's Desk Reference or Material Quarterly handed out by the drug representatives. Eleven percent of the 106 statements about drugs were inaccurate. All 12 inaccurate statements were favorably toward the promoted drug whereas 49% of the 79 accurate statements were favorable. None of the 15 statements about the competitor's drug were favorable, but all were accurate, which was significantly different than statements about promoted drugs. In a survey of 27 physicians who attended these presentations 26% recalled any false statements made by the pharmaceutical representative and 37% said information from the representative influenced them in the way they prescribed the drugs. In conclusion, 11% of the statements made by the pharmaceutical representatives about the drugs were different from information available to them. Physicians in general failed to recognize these inaccurate statements. 22263[med, pha] The amine hypothesis of affective disorder suggests a deficiency of cerebral noradrenaline and serotonin as the underlying mechanism for the development of depressive symptoms and remains the most widely accepted model for understanding the biology of depression and therapeutic action of antidepressant treatment. Tetrahydrobiopterin is an essential cofactor for the conversion of phenylalanine to tyrosine and the hydroxylation of tyrosine and tryptophan, the rate limiting steps in the formation of serotonin, noradrenaline and dopamine. BH4 is important for regulating the presynaptic release of neurotransmitters from nerve terminals. BH4 deficiency prevents neurotransmitter synthesis showed by atypical hyperphenylalaninaemias of infancy. Increased biopterin levels have been found in the serum and postmortem brain of young patients with Alzheimer's and Parkinson's diseases. Another researcher has observed decreased urinary biopterin in bipolar patients and low BH4 in postmortem temporal cortex of subjects with a history of severe depression. Raised total biopterin has been found in the urine and plasma. Three out of 4 studies measuring neopterins found levels to be raised in the urine or serum of depressed subjects. There has been improvement in depressive symptoms following treatment with BH4 and evidence that antidepressants increased BH4 turnover in vitro. In conclusion, neopterin:biopterin ratio can be used as an index of functional integrity of the BH4 biosynthetic pathway. BH4 is essential for the biosynthesis of amine neurotransmitters in the regulation of presynaptic release from nerve terminals. Folate is essential for the regeneration of BH4. Within depression the raised N:B ratio indicates reduced availability of BH4 and reduced functional activity of amine neurotransmitters. The raised N:B ratio may be related to interalia to activated cellular immunity causing an increase in neopterins and to reduced BH4 caused by decreased folate which commonly occurs in depression. 22679 [neu] This is a review article noting that the recent popular debate regarding trans fatty acids has lost sight of the real problem, that is, saturated fats. The concern is that transfatty acids: 1. Behave like saturated fats. 2. Independently increase the risk to coronary heart disease. 3. May cause other undefined harm to health. In Australia, there is really a low amount of trans fatty acids compared to other western countries; the question is how this country should incorporate trans fatty acids. Normally polyunsaturated fatty acids are in the cis configuration at the carbon double bond which means the hydrogen atoms point in the same direction. In the trans fatty acids the atoms point in opposite directions. A small change like this in oleic acid can reverse its cholesterol lowering potential. Trans fatty acids are produced during the hydrogenation of oils in the manufacture of margarines. It is noted that þ of our dietary trans fatty acids are derived from dairy, beef and sheep fat. Two percent of the total energy intake in the Australian diet is from trans fatty acids compared with 15% from saturated fats; one-third of this is from ruminant sources. Consumption of margarine and other hardened oil products provides approximately 1/10th of the fatty acids likely to raise plasma cholesterol. The author feels that switching from margarines to butter is a þridiculousþ suggestion by some experts. The polyunsaturated fatty acids and monounsaturated fatty acid structures are considerably superior to those of butter with regards to their influence on LDL cholesterol. In the same breath the author suggests that the industry needs to come up with technologies that do not add trans fatty acids to the contents of foods. Trans fatty acids should be counted as saturated fatty acids in calculating the polyunsaturated to unsaturated fats in margarines. The author feels that too much has been stated regarding the claim that trans fatty acids raise the risk to coronary heart disease. In conclusion the author feels that patients should be told that trans fatty acids will raise LDL cholesterol concentrations and some of this will come from margarines and products made from margarines. At present we are far from knowing that the small amount of trans fatty acids in our food supply can cause heart disease other than by raising LDL cholesterol concentrations. There is no other proved adverse consequences of trans fatty acids. In general we should eat less fat, avoiding undefined sources of fat from fast foods and other quick-take-out establishments. Mostly, saturated fat should be avoided; eating butter is not safer than quality poly or monomargarines. 21360 [car, nut] This study evaluated 68 Alzheimer's disease patients, 46 who were living and 22 who were deceased, and 34 nondemented control subjects. Head injury was reported in 20 of the Alzheimer's disease patients (29%) and in 1 control subject (2.9%). Twenty percent of the familial and 43.5% of the sporadic Alzheimer's disease cases reportedly had a head injury prior to death. Head injury had no effect on the age of dementia onset in subjects. This data suggests that head injury may be a predisposing factor to Alzheimer's disease. 22711 [neu, psy] Forty-one out of 81 elective patients for coronary artery bypass surgery in a randomized, double-blind, clinical trial were given intravenous magnesium sulfate at 4.2 gm before cardiopulmonary bypass followed by an infusion of 11.9 gm of magnesium chloride until the first postoperative morning and a further 5.5 grams until the 2nd postoperative morning. Forty patients received magnesium sulfate only after bypass to a total of 2.9 gm at the first and 1.4 gm at the 2nd postoperative morning. A blood cardioplegia technique was used in both groups which included a bolus dose of magnesium chloride at a total of 2.4 gm and 2.3 gm to the high dose and low dose groups, respectively. Serum magnesium levels peaked in the high dose group on the first postoperative morning at 1.6 mmol/L, whereafter it declined to normal on the 3rd postoperative morning. Patients in the low magnesium group were normomagnesemic except after the start of bypass. Recovery to spontaneous rhythm after declamping of the aorta was better in the high magnesium group. Only 1 patient had ventricular fibrillation in the high magnesium group whereas in the low magnesium group 4 patients had ventricular fibrillation and 5 patients needed a temporary pacemaker. Atrial fibrillation was detected in 7.3% in the high dose group versus 25% in the low dose group within the first 48 postoperative hours. 24.3% in the high dose group and 45% in the low dose group had a total of 19 and 41 episodes of atrial fibrillation during the first postoperative week. Paired ventricular ectopic beats were detected during the first 24 postoperative hours in 42% in the high magnesium group and in 71.1% in the low magnesium group. 22600 [car, sur] This is a review article on the effectiveness of cholesterol- lowering diets. Two trials of dietary therapy utilizing intensive individualized counseling in persons at usual risk for coronary artery disease achieved 75 to 80% of the cholesterol lowering predicted by metabolic ward studies, and produced 5 to 14% reduction in total cholesterol levels. Four studies in high risk individuals exceeded the predictions and achieved a 4% to 17% reduction in total cholesterol levels. Six of 7 trials of diet therapy for secondary prevention had similar benefit. Four trials utilizing the population approach achieved smaller but often significant reductions in total cholesterol levels of 1 to 11%. The effectiveness of diet is enhanced when individualized counseling is utilized, follow-up is maintained and weight reduction is achieved. It is noted that the efficacy of a cholesterol-lowering diet has been clearly shown in the metabolic diet studies where dietary intake can be maximally controlled and confounding variables can be taken into account. Even though approximately 10% of the population at large and a higher percentage of patients in tertiary lipid clinics are diet resistant, dietary modification can still play an important role in lowering cholesterol levels and reducing the risk to coronary heart disease around the world. 21969 [car] This study evaluated adipose tissue samples from 671 men with acute myocardial infarction aged 70 years or less, and 717 men without a history of acute myocardial infarction. There was no overall difference between cases and controls with respect to the proportion of adipose tissue C18:1 trans fatty acids. The risk of acute myocardial infarction did not significantly differ with the amount of trans fatty acid intake between the highest and lowest quartiles. After adjusting for certain variables, there tended to be an increased risk of acute myocardial infarction in the upper quartiles of the C18:1 trans fatty acids, though it was not statistically significant. The authors conclude that there are definitely considerable differences between countries in dietary intakes of trans fatty acids, but these do not suggest a major overall effect of C18:1 trans fatty acids on the risk of acute myocardial infarction. The authors cannot exclude the possibility that a very high intake of trans fatty acids may have a significant impact on acute myocardial infarction. Further evaluation is needed before strong recommendations are made. 21735 [car] Vitamin E supplementation at 6,000 I.U. per day may reduce the clinical signs or decrease the incidence of degenerative myeloencephalopathy (EDM) in foals that are at increased risk from a dam that has produced foals that have had EDM. Some studies have reported lower serum vitamin E levels in foals affected with EDM. Vitamin E is required for the normal function of muscles, nerves, and the immune system. Vitamin E and selenium are part of a very important antioxidant defense system which protects against free radicals. In 1989 the National Resource Council's recommendations for vitamin E were 50 I.U./kg in the diet for maintenance and 80 I.U./kg in the diet for pregnant, lactating, growing or working horses. It is suggested that the maintenance level of vitamin E should be higher than this. 21755 [neu] This article gives 2 case reports of very low birth weight infants who had inadequate levels of plasma vitamin A and E. The infants had been receiving a parenteral multivitamin and mineral preparation at 1.5 ml/kg per day in a dextrose-amino acid solution. A different delivery system was tried, utilizing 2 ml/kg per day and infused for 6 hours from the first day of life. This latter system offered significant improvement in vitamin A and E levels during the first 28 days of life in very low birth weight infants. 21603 [nut, ped] This study evaluated 21 women who had experienced at least 3 vaginal candidiasis infections within the previous 12 months and 15 female control subjects. The authors found no difference in mean zinc concentrations of plasma and cervicovaginal secretions between the two groups. Zinc levels of plasma and cervical secretions had no correlation. These results do not confirm the previous hypothesis that zinc deficiency of the serum is a risk factor for recurrent vulvovaginitis. It is possible that the local zinc levels of the cervicovaginal secretions influence antifungal activity of third generation azole antimycotics. 21520 [gyn] This study evaluated samples of the isthmic part of the uterus from 42 pregnant patients not in labor, 31 patients in regular labor during a cesarean section and 37 premenopausal patients in whom a hysterectomy was performed. Magnesium concentrations dropped significantly during labor. Calcium concentration showed no significant change in the tissues during labor. Magnesium and calcium concentrations were significantly higher during pregnancy. The distribution of electrolytes in the myometrium differed significantly in from those the corpus, isthmus and cervix uteri. The authors conclude that the electrolyte concentration, specifically calcium and magnesium, in the myometrium depends on the place of removal. A low magnesium concentration in pregnant human myometrium might be a cause of premature labor. It is noted that during pregnancy there is a physiologic accumulation of water in the tissues and a significant decrease in the excretion of magnesium through the kidney. Magnesium requirement of the growing fetus, the placenta and the myometrium can be taken care of with a balanced diet, though in some cases magnesium supplementation may be needed. If premature labor ensues, increasing the magnesium calcium ratio may help in the shortening of the use of beta- mimetics. 22623 [obs] This study measured dietary iodine intake and urinary output, as well as thyroid activity, in 12 þliving foodþ eaters (individuals who consumed uncooked lactobacilli vegan food). The living food eaters were compared to omnivores. The living food eaters were divided into two groups. There was a high urinary iodine output group which urinated greater than 900 ug/d of iodine, and a low iodine group of less than 200 ug/d. Thyroid activity was within the normal range in both groups. Dietary iodine intake was related to seaweed consumption. The highest amount of dietary iodine seen in this study may be harmful for susceptible individuals. The amount of iodine consumed by the living food eaters did not reach the RDA levels. These living food eaters need to consume seaweed or take kelp supplements to achieve the recommended daily dietary allowances. These products should be consumed with caution, since they have a very high iodine content. 21685 [nut] This study evaluated the levels of plasma and milk vitamin E in women with insulin-dependent diabetes mellitus, women without insulin-dependent diabetes mellitus and healthy reference women. There was no difference between the groups for plasma vitamin E, which was in the normal range. Vitamin E (ug/g lipid) decreased by approximately 50% in all groups in 7 to 14 days. The trend for milk vitamin E was similar when expressed as ug/dl. Metabolic control of diabetes did not have a significant effect on mean milk or vitamin E concentrations. The results of this study showed that this group of women with insulin-dependent diabetes mellitus produced a milk with vitamin E content similar to the control and reference women. The authors conclude that the infant of a breast- feeding woman with insulin-dependent diabetes mellitus who was in good metabolic control during pregnancy and who receives good prenatal counseling is most likely to receive adequate vitamin E from the mother's milk. 22533 [gyn, ped, und] Most of the research that has been done on the brain and exercise focuses on the influence of exercise upon cerebral blood flow, neurotransmitter availability and neural deficiency. Exercise's influenced upon mental health and cognitive ability has been the primary area of research. Research suggests that exercise has a direct impact upon the brain. This direct effect may indirectly influence brain functioning via exercise. Exercise has an impact on cerebral blood flow, neurotransmitter availability, brain structure and neural efficiency. These changes are related to improved mental health and cognitive function. Future research needs to have a more concentrated focus so that the direct and indirect effects of exercise on brain function can be more clearly linked. Studies need to elucidate the precise mechanisms underlying improvements in cognition and define the exercise, the types of cognition that can be improved, and the populations which might most benefit from exercise. Exercisers have large increases in cerebral blood flow, increases in noradrenaline, and in animal models an increase the number of synapses per Purkinje cells, increased central nervous system inhibitory abilities, faster reaction times and longer P3100 event-related potential latency which is a measure of information processing in elderly fit individuals. 22194 [exe, neu, psy] This study evaluated sudden infant death syndrome (SIDS) in Hordaland, Norway, 3 years before and 3 years after a campaign to discourage prone sleeping. Before the campaign 64% of the random referenced infants were prone versus 8% after the educational program. The rate of SIDS decreased from 3.5 to 1.6 per 1,000 live births during this time period. Prone sleeping was not considered a statistically significant risk factor for SIDS before but was highly significant after the campaign. Prone sleeping is an important risk factor for SIDS but this association in epidemiologic studies may be missed if prone is the predominant sleeping position. 22277 [ped] This is a review article on the re-evaluation of macrocytosis. Macrocytosis with a mean corpuscular volume higher than 100 fL are found in 3 to 4% of the adult population. Thirty to 50% may not have an associated anemia. When results of B12 and folate are normal causes of macrocytosis include alcoholism, liver disease, drugs such as cytotoxic agents, zidovudine, myelodysplastic syndromes, marrow replacement, reticulocytosis from hemolytic anemias, acute blood loss, marrow nutritional response, hypothyroidism, aplastic anemia, sideroblastic anemia, arsenic or chlordane intoxication. A listing of multiple drugs are given that may result in macrocytosis. An algorithm for investigating macrocytosis starts with a mean corpuscular volume greater than 100 fL, a history and physical examination ruling out drug exposure, a hematologic profile, reticulocyte count and peripheral blood smear. If there are no macrocytes in the blood smear and reticulocyte count is normal then rule out artifacts for macrocytosis. If there are no macrocytes on the blood smear and the reticular count site is high then evaluate for hemolysis, bleeding or nutrition response to iron, folate or vitamin B12. If macrocytosis is present and there are round macrocytes, liver function test, T4, TSH studies and a detailed history of alcoholic consumption are done. If these are normal do serum B12 and folic acid studies. If these are low evaluate as needed as the Schilling test. If they are normal consider bone marrow or cytogenetic studies to rule out myelodysplasia. The authors note that folate and vitamin B12 deficiencies may rarely cause macrocytosis compared to alcoholism, liver disease, drugs or myelodysplasia. 22430 [hem] This study evaluated the effect of feeding 8 healthy young women a high protein diet of 1.55 g/kg body weight on vitamin B6 status. The 8 healthy women were in a metabolic unit and went on a depletion diet of less than .05 mg of B6 per day for 11 to 28 days followed by either animal-protein or plant protein diets with successfully increasing vitamin B6 intake at .5, 1.0, 1.5 and 2.0 mg/d for periods of 14 to 21 days. Animal protein sources were primarily from dairy and poultry while plant sources were primarily from beans. The plant protein diet does not elevate the vitamin B6 requirement over that required for the animal protein diet given the high amount of dietary protein used in this study. It was also found that .015 mg of vitamin B6 per gm of protein intake normalized most biochemical indices of vitamin B6 status including functional assessment. .020 mg/kg protein normalized all biochemical measures except for total urinary B6. Adding a margin of safety to either the .015 or the .020 mg/g protein intake would raise the vitamin B6 requirement for young women above the current recommended dietary allowance of .016 mg/g of protein. 22308 [nut] Human zinc deficiency as related to diet was recognized 30 years ago among adolescents in Iran and Egypt. This study comparing the dietary intakes of zinc with requirements suggest that many women and children are at risk of deficiency. Epidemiologic data associate low levels of plasma zinc with abnormal pregnancy outcomes. Controlled trials have shown that zinc repletion improves pregnancy outcomes. Low iron status, which is a common problem in women, has been shown to be associated with low zinc status. The author concludes that the hypothesis that zinc deficiency is a public health problem appears to be valid. The reasons for the lack of recognition of zinc deficiency being as prevalent as it is due to a variety of factors. The evaluation of zinc in relation to the environment and the host is not a usual component of clinical assessment. The risk of zinc deficiency is therefore not appreciated. Another problem is the insensitivity and difficulty of laboratory assessment of zinc status. Analysis of zinc in the plasma, leukocytes and other tissues requires special instrumentation. Plasma zinc, the most common measured index of zinc status, is insensitive. Plasma zinc is often in the normal range unless there is very severe zinc deficiency. Analysis of zinc in the leukocytes is more difficult and generally not available as a clinical tool. The clinical use of enzyme assays for the diagnosis of zinc deficiency has been disappointing. 22449 [nut] This study evaluated 23 chronic uremic patients on hemodialysis suffering from severe itching who received activated powdered charcoal at 6 gm per day. In 10 of the 23 patients the itching disappeared completely, and in another 10 there were partial relief. This relief occurred for several weeks after the discontinuation of the treatment. Only 3 cases were completely unresponsive. There was no significant side effects except for in 1 case. At present the mechanism is unknown. The authors conclude that activated charcoal by mouth is an effective and low cost therapy for patients with uremic pruritus. 22615 [der, nep] Quercitin and kaempherol constitute 2.5-3.8% and 6.0-6.4% of Podophyllin dry substance respectively. Podophyllotoxin is 12.7- 13.8% of Podophyllin dry substance. As approximately 10% of the amount of dry substance in Podophyllin, 20% is composed of 2 mutagenic flavonoids, Quercitin and Kaempherol. Self medication with purified podophyllotoxin .5% may be considered a first line treatment in well educated patients with external genital warts. 22749 [der] Sixty patients with pulmonary tuberculosis and 170 matched controls were evaluated for serum copper and zinc status. In patients with pulmonary tuberculosis the copper level was elevated to 125.33 ug/dl which was significantly higher than controls. Zinc in pulmonary tuberculosis was 81.02 Ug/dl which was significantly lower than controls. In sputum positive and negative individuals no significant difference for serum copper and zinc could be detected. The author suggests that high levels of copper and low zinc levels in the serum are implicated in the etiology of pulmonary tuberculosis. 22320 [inf, pul] This study evaluated 42 patients who were randomized into 2 groups. One group received an isocaloric and isonitrogenous placebo diet and the other group was fed the same diet supplemented with arginine at 1.25 gm per 100 ml, RNA at .12 gm per 100 ml, omega-3 fatty acids at 10.5% per 100 ml and omega-6 fatty acids at 8.3% per 100 ml. In those who received the placebo diet interleukin VI concentrations were significantly higher on days 3 and 7 and tumor necrosis factor alpha concentration on day 7. In contrast mean concentrations of interleukin-II receptor was significantly higher on days 3 and 7 and interleukin-I beta and interleukin-II on day 16 in the groups receiving the supplemental diet. The authors conclude that the diet with supplemented arginine, RNA and omega-3 fatty acids can modulate acute phase reaction as indicated by reduction in concentrations of tumor necrosis factor and interleukin-VI in the group fed the supplemental diet. Patients receiving the supplemental diet showed accelerated recovery in concentrations of interleukin-I beta and interleukin-II receptor. Supplementation of enteral nutrition with arginine, RNA and omega-3 fatty acids improved recovery from immune depression induced by cancer and operation. 22687 [can, sur] This article reviews factors that may aggravate atopic dermatitis, including irritants, airborne allergens, food, micro organisms, sex hormones, stress, sweating and climate. There is some controversy regarding the extent to w hich food may exacerbate atopic dermatitis. Reactions to food may be both allergic and non-allergic and are most often provoked by eggs, peanuts, milk, fish, soy and wheat. Elimination diets should be directed with careful attention to causative items. Consideration should also be given to the effects of such a diet on the patient, as it may cause social isolation, nutritional deficiencies, or lead to anaphylaxis if a nontolerated food is carelessly reintroduced. Daily stress can trigger itching and scratching. Relaxation exercises may be helpful in preventing severe attacks. Avoiding activities and situations that induce sweating, and time spent in favorable climates may reduce discomfort. Many factors may trigger atopic dermatitis. In patients not responding to conventional basic therapy, identification and removal of these factors is best enabled by careful examination and thorough history taking. 21443 [der] This study evaluated 233 pregnant women at high risk of developing proteinuric or nonproteinuric pregnancy induced hypertension or asymmetrical intrauterine growth retardation who received 2.7 gm of MaxEpa which is equivalent to 1.62 gm of eicosapentaenoic acid and 1.08 gm of docosahexaenoic acid. There was no difference between the placebo and the active treatment groups for the occurrence of proteinuric pregnancy induced hypertension, nonproteinuric pregnancy induced hypertension or the duration of pregnancy. The authors concluded there is no beneficial effect of fish oil supplementation in women at high risk of adverse outcomes for pregnancy but a small protective effect is possible. 22497 [gyn, obs] In evaluating 2,424 men's lipoprotein (a) levels, 113 men were found to have intermittent claudication. These men were older at entry, had higher systolic blood pressures and elevated lipoprotein (a) levels (46 vs 33 mg/dl). There was a higher rate of smoking and diabetes among men with intermittent claudication. The risk of intermittent claudication was doubled in men in the 2nd and 3rd tertiles of lipoprotein (a) concentration. High lipoprotein (a) levels are a significant risk factor for intermittent claudication in this population. 22660 [car] Forty-two subjects who underwent culture of gastric and duodenal aspirates as well as pH assessment had paired fasting breath hydrogen concentrations by gas chromatography within 7 days of endoscopy. Paired fasting breath hydrogen concentrations differed in terms of normality or abnormality in 21% of the subjects. Paired concentrations correlated significantly in overgrowth but not in culture negative subjects. Sensitivity for bacterial overgrowth was 4 to 29% and specificity was 71 to 100%. No correlation with gastroduodenal pH was found. The authors state that the clinical relevance of a single fasting breath hydrogen concentration is limited. The efficacy of paired measurements for gastric or small intestinal bacterial overgrowth is poor. 22694 [gas] In a rat model evaluating streptozotocin diabetic peripheral nerves it was found that a vitamin E deficient diet resulted in a rapid depletion of vitamin E in the plasma and sympathetic neurons and a slower depletion in sensory neurons and nerves. This depletion was associated with a reduction in reduced glutathione and an increase in conjugated dienes and hydroperoxides in the normal rats. Similar changes or accented abnormalities occurred in the diabetic nerves. These changes were more pronounced at 1 month than 3, and vitamin E supplementation did not prevent the abnormalities. Vitamin E depletion worsened nerve conduction abnormalities in both sciatic- tibial and caudal nerves. Sensory nerves were more affected than motor nerves. The authors state that this study supports the hypothesis that oxidative stress may cause neuropathy. This might be the mechanism in diabetic neuropathy. 21440 [end, neu] Nitric oxide is a simple chemical substance which was labeled in the past endothelium-dependent vasodilating substance or endothelium-derived relaxing factor. It is a product of the normal endothelial cell. L-arginine is converted to citrulline through a process of oxidation and nitric oxide is formed. Nitric oxide inhibits the adhesion, activation, and aggregation of platelets and promotes an antithrombotic property on the endothelial surface. Inhibition of nitric oxide synthase activity promotes the adhesion and emigration of leukocytes and also increase microvascular permeability. L-arginine impairs the proliferation of the vascular intima after aortic injury in rats. Patients with deficiencies might be treated first with the nitric oxide synthase substrate L-arginine, which has been shown to improve endothelium derived vasodilator function in animal models of pulmonary hypertension. Inhaled nitric oxide may be used as an alternative therapy for individuals who do not have enough residual nitric oxide synthase activity for L-arginine to be effective. 22912 [car] A rat model evaluated experimental allergic encephalomyelitis with the treatment of hyperbaric oxygen. Animals were exposed to two 3 hour 2 ATA treatments within 24 hours. There were 3 HBO protocols used: a 10 day preventive treatment, a 3 day preventive treatment and a 10 day symptomatic treatment. This study showed that HBO treatment does not reduce the blood brain barrier disturbance and cerebral edema in experimental allergic encephalomyelitis. It tends to provoke reversible blood brain barrier breakdown. Preventive HBO treatments result in modification of the course of experimental allergic encephalomyelitis possible by immune suppressive effect during the initial sensitization step. The HBO treatment generates oxygen free radicals. The variation in the intensity of the blood barrier injury might be due to differences in the animal's susceptibility to oxygen. 22712 [all, neu] In a double-blind study, 12 healthy volunteers who did not take any vitamin supplements, prescription medications or nonsteroidal anti- inflammatory agents were randomly assigned either a placebo or 400 I.U. of vitamin E daily. Susceptibility to the skin erythema and sunburn damage was assessed before treatment and after 1 and 6 months of supplementation. Erythema was produced by exposing the skin of the buttocks to increasing doses of ultraviolet B radiation. Each subject received a dose of UVB radiation 3 times the minimal erythema dose, and a biopsy of the exposure site was taken 24 hours later. Plasma levels of alpha-tocopherol were increased by 65% in the subjects receiving oral supplementation. There was no significant difference apparent in the minimum erythema dose between either group at pretreatment or at 1 and 6 months after treatment. The number of cells showing sunburn damage was not statistically different at any of the assessment intervals. The authors found no objective photoprotective effect of long term vitamin E supplementation at 400 I.U. per day. They do note that the administration of vitamin E alone may not be optimal since studies have shown that tocopherol is prone to degradation without the presence of other antioxidant compounds such as vitamin C. 22010 [can, der] This is an extensive review article on the role of calcium and blood pressure. The data has been taken since 1987. Intervention and epidemiologic studies are reviewed. Calcium in the diet, the effect of stress on calcium metabolism and calcium in hypertension of pregnancy are specific areas of focus. Calcium dysmetabolism and hypertension may be due to abnormalities in the regulation of extracellular calcium affected by parathyroid hormone, vitamin D and the renin-angiotensin system. It is noted that in pregnancy-induced hypertension there are clear abnormalities noted by hypocalciuria and large increases of intracellular free calcium. Calcium supplementation in certain studies has shown some benefit in lowering blood pressure in doses between 1 to 2 gm per day. Other than the potential development of kidney stones there appears to be no significant safety risk with calcium consumption. The dose ranges for calcium supplementation are not totally clear but there is no evidence to use more than 2 gm per day of calcium in any situation. In reports stating positive outcome to calcium supplementation, beneficial effects of calcium supplementation appear to be long lasting, but there is no documentation on long term effects of high calcium intake. From all available domestic and international data it appears that calcium from dairy products is the most reported source of calcium intake. In review, observational studies of large populations support the possibility that calcium intake plays a role in blood pressure. Contradictions occur in assessing calcium intervention studies in humans. The results have been inconsistent and in most parts negative with the exception of interventions in preeclampsia. There is not enough evidence at present to support calcium deficiency as a cause of hypertension yet its deficiency may exacerbate blood pressure/sodium sensitivity issues. Populations consuming the RDA of 800 mg of calcium per day for males and females greater than 25 years of age and 1,200 mg for pregnant females have a lower incidence of sodium sensitivity and lower prevalence of pregnancy-induced hypertension. There is no clear understanding of how dietary calcium affects blood pressure. Body weight reduction is still the single, most consistent, non- pharmacologic means of controlling blood pressure. Further research is needed on the role of sodium, calcium, potassium and magnesium, body weight and alcohol in blood pressure management. Calcium should be increased in pregnant females, especially when calcium intake is below the RDA. Intakes of calcium-rich foods, particularly dairy products, have been shown to be inversely related to hypertension. 21835 [nut, obs, ort] This study evaluated the glycemic index and triglyceride response in 30 noninsulin dependent diabetics who were given 50 gm portions of 5 cereal-green leafy vegetable combinations that are traditionally consumed in India. These foods include rice in the form of flakes and puffs, wheat bhakari (wheat flour kneaded, rolled out and shallowed fried), wheat bhakari stuffed with fenugreek, and spinach leaves. The puffed rice and wheat bhakari showed a higher glycemic response than a 50 gm glucose load. Rice flakes and wheat bhakari stuffed with green leafy vegetables had a much lower glycemic response. Puffed rice showed a higher glycemic response as compared with rice flakes and rice alone. The puffing of rice involves parching whereas flaking of rice involves pounding. The parching may alter structural changes which may be responsible for the increased glycemic response to puffed rice. Pounding flattened rice kernels may account for the lowering of the glycemic response. 21570 [end, nut] This study evaluated 25 dogs, 10 of which were supplemented with the EPA-ester at 100 mg/kg body weight per day for 8 weeks; 15 served as controls. After ingesting EPA for 8 weeks the ratio of eicosapentaenoic acid to arachidonic acid in platelet cell membranes was significantly increased. The EPA group had a reduction in the chemotactic response of neutrophils to leukotriene B4. Also in the EPA group the amount of 12-hydroxyeicosatetraenoic acid, one of the chemotactic products of arachidonic acid in the infarcted myocardium, was reduced to 40%. EPA treatment resulted in a significant reduction in the ultimate infarct size. In the EPA group the contractile function of the infarcted myocardium was preserved. Myeloperoxidase activity, which is a sign of infiltration of neutrophils into the infarcted myocardium, was less in the EPA group than in the controls. The authors conclude that dietary supplementation with eicosapentaenoic acid inhibits the ischemic myocardial damage through the inhibition of neutrophil infiltration in the damaged heart tissue. 21922 [car] Eleven patients between 38 and 67 years of age were evaluated during diagnostic coronary arteriography. All patients had stable effort angina and significant coronary artery disease, defined as the presence of greater than a 70% stenosis in one of the major coronary arteries. During the first pacing, all 11 patients complained of angina at a mean heart rate of 134 beats per minute, with ST depression of 1.8 mm. Angina and ST depression were associated with an inversion from lactate extraction to production from ischemic myocardium. An intravenous infusion of magnesium sulfate was begun at 0.4 gm per minute. A second pacing was begun. At the peak of the second pacing, angina was completely prevented in nine patients. In these patients, mean ST segment depression after the interruption of pacing was 0.5 mm, and the mean lactate production of 12% at the peak of the first pacing was converted to a net lactate extraction of 10%. Only 2 of the 11 patients complained of angina associated with ST depression and lactate production. In summary, this study shows that magnesium sulfate infusion at a rate of 0.4 gm per minute prevents pacing-induced myocardial ischemia in patients with coronary artery disease, and this effect is not mediated by an increase in coronary blood flow. The mechanism of magnesium's benefit is possibly due to a reduction in myocardial oxygen requirements, but other mechanisms, such as a direct protective effect on the ischemic myocardium, cannot be excluded. These results provide additional rationale for treating tachyarrhythmias with high-dose magnesium infusion in patients with coronary artery disease. 21760 [car] Irritable bowel syndrome and sexual abuse are intertwined. It is suggested that patients with refractory, severe, irritable bowel syndrome ought to be asked whether they have been a victim of sexual or physical abuse. This conclusion was reached by a consensus panel in a just-completed but not-yet-published report sponsored by The Functional Brain-Gut Research Group of the American Gastroenterological Association. The recommendation was endorsed by outside experts. There is a body of data suggesting that 20 to 54% of patients with irritable bowel syndrome, when asked, will report a history of child molestation or a form of sexual or physical abuse. Certainly any physician would ask a patient about a history of chest pain; it is just as important to ask IBS patients about a history of abuse. Irritable bowel syndrome accounts for approximately half of the typical gastroenterology practice patients. A community survey suggests that 15 to 20% of American adults have irritable bowel-like syndrome. Once the history of sexual abuse is determined one can recommend experts in the fields that deal with this kind of social and psychological event. Published studies of sexual abuse and irritable bowel syndrome in the general population include a survey of nearly 1,300 people who underwent a routine health appraisal at Kaiser Permanente. A study of 217 consecutive Mayo Clinic patients and a population based study of 819 randomly selected residents in Olmstead County, Minnesota found that a history of sexual abuse increased the likelihood of a functional bowel disorder several times. Other studies are noted. 21898 [gas, psy] A food frequency questionnaire assessed daily fruit and vegetable consumption among 23,699 adults in 16 U.S. states. This random telephone survey showed that men consumed fewer servings per day (3.3) than women (3.7). Only 20% of the population consumed the recommended 5 or more servings. There was interstate variation in consumption; there was lower consumption among the young and less educated. The authors conclude that efforts are needed to educate Americans, especially younger adults and those with lower levels of education. The author notes a diet rich in fruits and vegetables is associated with a lower risk of chronic disease. The Year 2,000 Objective for the United States includes increasing the intake of fruits and vegetables to 5 or more servings per day. In this population-based study of U.S. adults from 16 states only about 1 in 5 adults reported an intake of 5 or more servings of fruits and vegetables per day. In fact, only 8% of the population was aware of the 5-a-day recommendation. 21886 [nut] The immune system is equivalent in its size and daily activity to a large organ that produces billions of new cells each day. There is significant evidence that severe deficiencies of single nutrients such as zinc, iron and vitamin A can depress measures of immunity and predispose life threatening infections. Researchers at Cornell have shown that depression of delayed hypersensitivity skin test responses (DHST) in older men exposed to ultraviolet radiation can be prevented by daily consumption of 30 mg of beta-carotene daily. Oregon State University researchers have shown that vitamin B6 at 50 mg per day can significantly enhance in vitro lymphocyte proliferative responses to several mitogens. In another study doses of vitamin E at 60, 200 or 800 I.U. per day increased DHST responses of antibody titers in vaccinated older adults. At 800 mg per day of vitamin E the mitogen responses improved only. Daily consumption of multivitamin and mineral supplements for 1 year by older men and women showed enhanced DHST and mitogen responses. These beneficial effects were reduced and delayed by ingestion of 15 or 100 mg of zinc each day. A study in Newfoundland found that consuming a multivitamin supplement for 1 year increased the mitogen responses, interleukin-II production, natural killer cell activity and antibody responses to the influenza vaccine. The supplemented individuals had fewer days of illness due to infectious disease. In a contrasting study older subjects consuming multivitamins for 4 months did not experience reduced incidence of infections. This may be due to the short duration of the supplementation. The author has found that DHST responses are significantly enhanced in older men and women by daily use of multivitamin and mineral supplements for 1 year. This cumulative data suggests the possible need for higher RDA levels of micronutrients to optimize immune responses in elderly subjects consuming their usual diets. The author recommends: 1. Placebo controlled clinical trials. 2. High dose single nutrients may improve immunity in weeks to months. 3. Some micronutrients may interfere with the beneficial effects of others. 4. Low to moderate doses of multivitamin supplements may require up to 6 months or a year or more for the beneficial immune effects. 7. High and even low dose micronutrient supplements can enhance immune function in the absence of underlying deficiencies. 22215 [can, imm] This study found in 7,264 men over a 12.75 year follow-up 167 major strokes of which 43 were fatal in men between 40 and 59 years of age. Current smokers had 4-fold relative risk of stroke compared with never smokers. Ex-cigarette smokers showed lower risk than current smokers, but showed excess risk compared with never smokers. Those who switched to a pipe or cigar smoking showed a significantly increased risk similar to that of current life smokers. Primary pipe and cigar smokers almost all showed an increased risk. The benefit of giving up smoking completely was seen within 5 years of quitting with no further consistent decline in risk thereafter. This was dependent on the amount of tobacco smoked. Light smokers at less than 20 cigarettes per day reverted to the risk level of those who had never smoked. Heavy smokers retained a more than 2-fold risk compared to never smokers of a stroke. The age-adjusted relative risk of stroke in those who quit smoking during the first 5 years of follow-up were reduced compared with the continuing smokers. The benefit of quitting smoking was seen in normotensive and hypertensive men. The absolute benefit was greater in hypertensive men. Smoking cessation is associated with rapid and significant benefit in decreasing the risk of stroke particularly in light smokers of less than 20 per day. 22810 [car, cer] There is a debate currently going on whether food stamp recipients should be allowed to buy vitamins and minerals with their food stamps or food only. Some concerns is that the poor might get too much of supplements and have toxic reactions while other researchers feel that food stamp recipients should not be denied these substances with potential health benefits. The food supplement industry is supportive of this issue. It would provides more options to food stamp recipients. 22998 [nut] Eleven newborns with respiratory failure and severe persistent pulmonary hypertension were given a loading dose of 200 mg/kg of magnesium sulfate over 20 minutes followed by a continuous infusion of 20 to 150 mg/kg per hour to obtain a blood level between 3.5 and 5.5 mmol/L. The duration of treatment was 75.5 hours. Mean PaO2 values significantly increased from 42.6 before the treatment to 70.3 mm Hg after 24 hours with no change in pH or Pco2. Oxygen index and alveolar-arterial oxygen gradient were significantly lower after 24 hours from 46.8 to 28.0 and from 624.3 to 590 mm Hg, respectively. Mean airway pressure was significantly reduced from 19.5 to 13.9 cm H2O after 72 hours. The mean ventilatory time support was 131 hours and the mean total oxygen dependency was 10 days. No adverse effects or systemic hypotension was noted. All the infants survived and their neurodevelopment was normal at 6 and 12 months of age. The authors conclude that magnesium sulfate is a nonaggressive and low cost treatment of short duration which is easy to apply. 22566 [car, pul, ped] This study evaluated 90 patients with major depressive disorder. Sixty-eight of these individuals were seasonal and 22 were nonseasonal. The subjects were evaluated before and after morning light between 6 and 8 a.m. or evening light between 6 and 8 p.m. for 10 days in a room with a luminance approximately 1500 lx at eye level. In depressed patients with seasonal pattern improvement there was more improvement in nonsignificant nonseasonal patterns which suggests a specific nonplacebo effect of light treatment in depressed patients with seasonal patterns. There were no significant differences in outcome when light treatment was given in the morning or evening. There was no differences between patients with and without atypical symptoms such as carbohydrate craving or increased appetite. Depressed patients with a seasonal pattern responded to 10 days of the light treatment. These patients will be followed to see how long after treatment how many will remain well and how many will suffer a relapse. 22488 [psy] This study evaluated 185 newborns and their mothers with tooth filling surfaces between 0 and 780 mm2. Mothers and newborns showed a highly significant correlation between the median value from .4 resp. .5 ug/Hg/L. The placenta has a retention capability up to 10 times higher mercury values and a low positive correlation to amalgam surfaces. There was no relationship between the blood values of the women and the children and the size and the surfaces of amalgam fillings. A high consumption of fish led to higher mercury values in umbilical cord blood even in mothers without amalgam fillings. Symptoms of diseases such as headaches, allergies and eczemas occurred in both those with and without amalgam fillings. All women gave birth to healthy children. The authors feel that some of the concerns regarding heavy metal contamination during pregnancy are not justified. 22706 [dent, gyn, ped] Nitric oxide can be synthesized from L-arginine. Nitric oxide comes in the vascular endothelium and is important in the regulation of blood flow. Nitric oxide plays an important roles in physiologic regulation of local blood flow and blood pressure, especially during exercise and in response to sheer stresses and other factors in arterials. Nitric oxide is involved in the neurogenic control of the microcirculation through autonomic efferent nerves and it contributes to vasodilation and inflammation associated with activation of sensory nerves. Excess nitric oxide can compromise circulatory function in septic shock, during transplant rejection and during myocardial ischemia and reperfusion. Immunosuppressant drugs like cyclosporin A inhibit the expression of nitric oxide synthase which is derived from L-arginine. Disturbances in the activity and inducible nitric oxide synthase in the arterial wall can accompany the development of atherosclerosis, vasospasm, and thrombosis, and may contribute to some forms of hypertension and diabetic vascular disease. The adversity of the nitric oxide defect of therapeutic agents including angiotensin converting enzyme inhibitors offers promise in protecting against some manifestations of vascular disease. 22878 [car] Vitamin E is the term used for 8 naturally occurring fat soluble nutrients. Alpha-tocopherol is the predominant in this group and has the highest biological activity. Most of plasma vitamin E is in LDL and HDL. Vitamin E may prevent the initiation or progression of spontaneous atherosclerosis. This theory is based on in vitro data. Vitamin E influences the response of vascular endothelial cells, leukocytes, vascular smooth muscle cells and the modification of lipoproteins, especially LDL. This latter could contribute to the initiation/progression of atherosclerosis. In vivo studies are required to firmly establish vitamin E's anti-atherosclerotic properties and therapeutic potential. 21467 [car] Ten unselected consecutive patients between 25 to 58 years of age with child's grade C cirrhosis, who were being assessed for liver transplantation, were evaluated for whole blood manganese concentrations. In these patients with liver cirrhosis there was a significantly increased level of whole blood manganese 34. ug/L versus 10.3 ug/L in the controls. Pallidal signal intensity correlated with blood manganese. Brain tissue samples showed the highest manganese concentrations in the caudate nucleus followed by the quadrigeminal plate and globus pallidus. Manganese accumulates within the basal ganglia and liver ganglia in liver cirrhosis. The similarities between manganese neurotoxicity and chronic hepatic encephalopathy suggested this metal may play a role in the pathogenesis of chronic hepatic encephalopathy. Chelating agents may prove to be a therapeutic option to prevent or reverse this neuropsychiatric syndrome. 22961 [neu, tox] It is noted that intensive exercise has an effect on zinc metabolism. High levels of constant exercise can have long term effects on zinc metabolism. Runners are noted to have lower zinc levels than controls. Long term endurance training has been shown to reduce resting serum zinc levels in both male and female athletes compared to sedentary controls. Zinc is needed for several enzymes and energy metabolism. Low zinc levels would result in reduced endurance capacity theoretically. Zinc deficiency may be related to muscular fatigue. These authors have shown that daily high and maintained physical training over 7 months shows considerable change in the immune system of elite athletes which is accompanied by psychological and a biochemical stress level. The mechanisms of muscular fatigue may be implicated in the cause of chronic fatigue. 22838 [exe, imm] This study evaluated 10 infants with persistent pulmonary hypertension who were not receiving protein or amino acids for at least 24 hours and compared their plasma arginine concentrations to 8 control infants without persistent pulmonary hypertension receiving similar nutrition. Plasma arginine concentrations were 32 and 52 umol/l in infants with persistent pulmonary hypertension and control infants respectively. There were no other significant differences in the concentration of plasma amino acids. Infants with persistent pulmonary hypertension who were later treated with amino acid infusions had plasma arginine concentrations at 115 umol/l. It is noted that nitric oxide, which has shown some benefit in the treatment of infants with persistent pulmonary hypertension, is synthesized in the body from the amino acid L-arginine. 21408 [ped, pul] In 36 nonexercising subjects with an average age of 36 years, bone mineral density was markedly weight dependent contributed to by both fat and lean tissue. Percent fat tended to be positively related to areal bone mineral density, where as the percent lean was inversely related to this index. Percent fat was positively related and the percent lean was negatively related to bone mineral density/height throughout the skeleton including the femur. In 63 exercising subjects with an average age of 33 years, fat mass and lean mass were unrelated to bone mineral density/height. The percent lean was positively correlated with bone mineral density and the bone mineral density/height in the femoral neck. The authors conclude that bone density is only associated with fat mass in sedentary women. In exercisers, femoral neck density is related to lean mass, probably due to the effects of weight-bearing exercise on both of these variables. 22669 [end, exe] This article comments on a previous report that acute tryptophan depletion reversed antidepressive induced remission in patients with depression. The reappearance of the depressive symptoms were more often seen in depressed patients treated with serotonergic antidepressants. The authors tested acute tryptophan depletion in 10 patients with bipolar disorder. They were all in remission and the duration of their illness was 14 years on the average. All the patients had been euthymic for the last year and they were all treated solely with lithium carbonate at a mean dose of 930 mg per day. The study was a double-blind, counter balance, placebo- controlled trial. Each subject consumed a low protein diet during the day proceeding test days which were 1 to 2 weeks apart. Lithium levels did not differ significantly between the 2 groups. Plasma tryptophan concentrations were elevated by 39% at 5 hours after ingestion of the control mixture while the tryptophan deficient amino acid resulted in an 85% reduction in total plasma tryptophan levels. Despite marked decrease in tryptophan concentrations tryptophan depletion in the patients with bipolar depression were stable while on the lithium therapy and did not induce any significant changes in effect of symptoms. These negative effects were in sharp contrast with those reported by others in 1990 on the reversal of the therapeutic effect of antidepressant treatments by tryptophan depletion. The differences in the 2 studies may be accounted for not only by the differences in the pharmacologic properties of the antidepressants and lithium but also by other methodological differences. It is possible that the effects of tryptophan depletion may be too brief to effect mood stability in patients in remission for a year or more. This data is consistent with the relatively modest contribution of serotonin versus other neurotransmitter systems and the mechanism of /action of long term lithium treatment. The results suggest that the therapeutic effects of long term treatment with lithium do no depend primarily on the serotonin availability in the central nervous system. 22349 [psy] This is a review article on the role of the heavy metals such as cadmium, gold and mercury and autoimmunity. In animal models cadmium treatment of rats and mice result in autoimmune responses. There is no absolute evidence that renal damage from human exposure to cadmium results in autoimmune disease. More clear cut autoimmune effects of preparations containing gold salts have been widely used in arthritis. Gold may cause autoimmune thrombocytopenia, immune complex-mediated glomerulonephritis and other autoimmune disorders. There is solid evidence that mercury can cause autoimmune disease in humans and experimental animals. There is probably a combination of factors, rather than a single mechanism involved in the induction of autoimmune responses with exposure to heavy metals. The inductive event is the exposure to the metal in an individual that is genetically predisposed. Chronic exposure is an important factor, and could take place over several months if not years. The metal may act in association with other environmental factors. Then there is probably activation of the cytokine cascade, with its effects on T and B lymphocytes. Autoantigens are released. Subsets of helper T lymphocytes are stimulated, followed by activation of the suppressor cells and proliferation of B lymphocytes. Therefore exposure to heavy metals may result in autoimmune responses and disease. It is not known why some metals can induce autoimmune responses and others do not. At present there are no published articles of autoimmune responses for silver, arsenic and cobalt. 22096 [auto] There are approximately 1.2 million chemical industrial workers throughout South Africa. In a survey of 78 workers in a chemical factory ocular disorders were more prevalent in the exposed workers (73.1%) than the nonexposed workers (43.6%). Of these ocular disorders found 40.8% were attributed to occupational exposure to chemicals. Occupational exposure to chemicals should be reduced and exposure protocols at work revised in order to reduce the prevalence of occupational related eye disorders. 22282 [env, oph, tox] In a rat model of glomerulosclerosis induced by Adriamycin, treatment with D-à-tocopheryl was started 1 day before or 1 day after the Adriamycin injection. This had the effect of reducing serum total cholesterol and triglyceride levels as well as ameliorating the glomerulosclerosis that occurred in rats with Adriamycin-induced progressive renal failure. The vitamin E clearly prevented the renal deterioration in the rats in this model. Vitamin E dosage was 500 I.U./kg/d. 21861 [nep] This article reviews the importance of exercise and mobility in the treatment of low back pain. It notes that bed rest and inactivity should play a relatively small role in the treatment of back pain. Physical exercise and "work hardening" programs have shown to be important for treating low back pain and getting the individual back to work. There is evidence for a role of low back pain in the acute treatment of "mechanical" low back disorders. Manipulative procedures have been shown to bring about more rapid pain and functional relief compared with conservative therapies. Over a longer time frame this advantage appears to disappear. The area of benefit for manipulation appears to be the acute low back when there is restriction to a range or ranges of motion. It is noted that most acute back pain patients recover spontaneously. Mobilization and manipulation are particularly useful in speeding up the recovery and returning to activity. Manipulation of chronic lower back pain appears to be of lesser success. The use of exercise in the treatment of low back pain and rehabilitation is overwhelming. The tissues of the vertebral column need the stresses of exercise, even under conditions of back pain. Numerous studies have shown the harmful effects of disuse on the spinal tissues, and that exercise usually does not increase low back pain. Lumbar function improves during exercise regimes. Low stress mobility exercises play an important role in the early treatment of acute low back pain by insuring the integrity of the musculoskeletal system. In one study 90% of patients subjected to vigorous exercise regimes had a good or excellent outcome based on measurement criteria, and there was a 92% return to work. Four of the 6 patients treated unsuccessfully who went to surgery were found to have spinal stenosis. This particular study is a good model for use of conservative exercise therapy, even when there is a clear diagnosis of a condition such as disk herniation. It is probable that surgery should be reserved for patients in whom function has not been improved through an intensive physical exercise rehabilitation program. 22856 [exe] This study evaluated 14 marathon runners, 12 soccer players, 9 wrestlers, 9 basketball players and 16 controls for vitamin C intake and serum and excretion levels. There was no significant differences in vitamin C status among the variable sport groups or between the sports groups and controls. Only 3 of 44 athletes had ascorbic acid intakes below the recommended dietary allowance of 60 mg per day. The authors conclude that ascorbic acid status is similar in athletes and controls and that vitamin C beyond the normal, daily intake may not be necessary. 21829 [exe] Dr. Pike, a researcher at the University of Southern California School of Medicine at Los Angeles, believes that the way to prevent breast cancer is to lower estrogen and progesterone levels. Exercise may accomplish this, as might a diet very low in fat and high in fiber. Drs. Pike and Bernstein did a study evaluating 545 women who developed breast cancer by the age of 40 and an equal number of healthy controls. The risk of breast cancer for women who exercise at least 4 hours per week (35 minutes per day) was found to be nearly 60% less than sedentary women. It is hoped that a large number of American women will adopt a low fat exercise-oriented lifestyle on their own. 21387 [can, exe] This study compared 116 cases of bladder cancer to 232 controls for the risk of occupational exposure. There was a significantly elevated odds ratio for exposure to pyrolysis and combustion products. In women, there was an elevated odds ratio for ink exposure. 21594 [can] This study evaluated 336 men with prostate cancer compared to 1,098 matched controls for their relationship to prostatic specific antigen. Sensitivity for the entire 10 year follow-up, at a cut off of 4 ng/mL, was 46% for total cases. Sensitivities for detection of total, aggressive and nonaggressive cancers during the first 4 years were 73%, 87% and 53%. The overall specificity of prostatic specific antigen was 91%. The estimated mean lead time for all cancers was 5.5 years. Only 40% of the cancers that were detected more than 5 years from baseline were nonaggressive. Compared with men with prostatic specific antigens less than 1 ng/mL, those with PSA levels between 2 and 3 ng/mL had a relative risk of 5.5. Research found that a single prostatic specific antigen measurement was highly informative. A single PSA level would have detected 80% of all aggressive cancers diagnosed within 5 years and about 50% of the aggressive cancers appearing as much as 9 or 10 years later. Specificity was also high. Only 96 of the 1,098 men who remained free of prostate cancer diagnosis through the 10 years had a false- positive test. These results support the conclusion that the prostatic specific antigen has the highest validity of any circulating cancer screening marker discovered to date. Efforts to identify cost effective screening strategies incorporating the prostatic specific antigen are warranted. 21675 [can] Colchicine's main pharmacologic property is the ability to block mitosis in metaphase because the mitotic spindle fails to form. Cells with the highest rate of division are earlier effected thus preventing the destructive effect of infiltrating neutrophils. Colchicine also prevents the release of histamine-containing granules from mast cells and also the processes involved in the translocation of granules by the microtubular system. The inhibition of tubulin polymerization induced by colchicine prevents intracellular events linked to the function of cytoskeleton including the spread of signals from surface cell receptors to the cytoskeleton, transportation and translocation to the cell membrane and the secretion of molecules via the tubulin system. A direct consequence of this cytoskeleton disruption is the change of cell shape observed also in the glomerular epithelial cells by electron microscopy. Colchicine has been shown to prevent renal allograft rejection by inhibiting adhesion molecules function on epithelial surface. Cultured endothelial cells pre-exposed to colchicine and then challenged with interleukin 1B show a down-regulation of cell surface expression of intracellular adhesion molecule-1 and endothelial leukocyte adhesion molecule. The authors theorize that colchicine in some way inhibit the development of acute experimental glomerulonephritis induced by mesangial trapping of IgA lectin aggregates. This may be due to the inhibition of binding of these complexes to mesangial IgA and lectin receptors which are likely to be disturbed by tubulin depolymerization induced by Colchicine. Colchicine might inhibit integrin expression on mesangial cells with modifications in renal hemodynamics and mesangial channels macromolecular flux, inhibiting the trapping of IgA/lectin complexes and the mesangial cell responses with subsequent nephritogenic process. This rat study showed that pretreatment for 4 days with colchicine by mouth inhibited the development of IgA mesangial deposits. The protective effect of colchicine may be due to the inhibition of binding of the aggregates to IgA and lectin receptors expressed at the surface of the mesangial cells. Another effect might be mediated by the inhibition of integrin expression on the mesangial cells. It may also be that the protective effect of colchicine on the development of experimental IgA nephropathy might be mediated by an inhibitory effect on mesangial cell surface integrins expression, with subsequent modification of the binding cell matrix and the focal contacts between mesangial cells and GMB, which maintain the structure and function of the glomerular tuft. The modifications in renal hemodynamics and mesangial channel macromolecular flux might inhibit the trapping of IgA/lectin complexes, the mesangial cell response and the subsequent nephritogenic process. 22637 [imm, nep] Malnutrition worldwide is the most common cause of folic acid and vitamin B12 deficiency; this affects large areas of Asia and the African continent. In these areas malnutrition of folate is so extreme that the association between intake and requirement is very evident. Elsewhere the imbalance may not be so obvious and other causes have to be considered. In Africa, the Americas and Asia ¬ to more than « of some of these populations are deficient in folic acid, the worst being southern India. In western societies about 10% have inadequate intake of folic acid. The reasons for inadequate intake may be cultural, religious or socioeconomic. Up to 90% of folic acid may be destroyed by cooking; a significant amount of vitamin B12 is also lost to cooking methods. Maybe as little as 50% of either of these nutrients is absorbed from a mixed diet. There is a greater need for folate supplementation than vitamin B12. Recently subclinical deficiencies have been diagnosed by subtle metabolic changes, especially in the elderly. These new metabolic indicators include homocysteine and methylmalonic acid. Methylmalonic acid is specific for vitamin B12 whereas homocysteine elevation can relate to other B vitamins including folic acid. The screening of elderly populations has shown a high incidence of elevated methylmalonic acid and homocysteine. Elevated methylmalonic acid can occur in renal failure, hemoconcentration and small bowel bacterial overgrowth. Homocysteine elevations can occur in renal failure, hemoconcentration, vitamin B6 deficiency and cerebrovascular disease. Other methods for detecting vitamin B12 deficiency include cystathionine and 2-methylcitric acid assays. It is too early to determine whether they are more specific than homocysteine and methylmalonic acid levels. It is clear that no one test will be the single answer for all cases of possible vitamin deficiency. The more tests that are applied the more likely a definitive diagnosis will be reached. With regards to nutritional folic acid and vitamin B12 deficiency, it is doubtful whether required acceptance of substantial changes and dietary habits will ever be accomplished. Fortification of staple foods such as maize and flour with folic acid may be beneficial for pregnant women and may have a wider application. Until this is done, reduction in neural tube defects should be attempted by supplementation of folic acid. Folic acid supplementation may become widespread for vascular disease. The concern regarding neuropathy in cobalamin-deficient subjects on high-dose folic acid has been exaggerated, but patients on such a regimen need supervision. The addition of cobalamin to foods should be also more widely practiced. Refining laboratory diagnosis will lead to many more atypical cases of vitamin deficiency being discovered and their causes determined. 21339 [nut] This study compared coronary risk factors in a randomly-selected group of 247 migrants from the Indian subcontinent of Punjabi living in West London and 117 of their siblings living in the Punjab in India. Those in the West London group had a greater body mass index, systolic blood pressure, serum cholesterol, apolipoprotein (b), lower HDL cholesterol and higher fasting glucose than siblings in Punjab. Insulin sensitivity was lower in men in the West London group than their counterparts in India. Indians in West London had lower beta cell function than those in Punjab. Serum lipoprotein (a) concentrations were similar in both areas. The lipoprotein levels, though, were higher than white European populations in the United Kingdom. The authors note that increases in serum cholesterol after migrating from India increased coronary risk by high serum lipoprotein (a) concentrations and greater insulin resistance. Such between- country comparisons are an important means of establishing coronary risk factors. In conclusion, body weight, serum cholesterol and blood pressure increased in Indians who migrate to the United Kingdom. They have higher lipoprotein (a) levels than indigenous populations and this is uneffected by migration. Their insulin resistance shows as an increase in blood glucose and an decrease in HDL cholesterol. On migration, they develop a coronary risk factor similar to that of the host community which unmasks the underlying genetic risk of coronary heart disease, resulting in high lipoprotein (a) levels and a predisposition towards insulin resistance. 21825 [car] This study evaluated 54 children who had not been previously vaccinated and who were egg allergic. They were given the MMR vaccine in a dose of .5 ml. All 54 children had positive skin testing with egg. Of the 17 children who underwent skin testing with the MMR vaccine 3 had positive results. All 54 children received the MMR vaccine as a single, subcutaneous injection. None had immediate or delayed adverse reactions. The MMR vaccine can be safely administered in a single dose to children with allergy to eggs. 22362[all, inf] This study evaluated 11 healthy men between 21 and 32 years of age during a 90 day metabolic suite study. Daily copper intake for the first 24 days, the next 42 days and the last 24 days of the study was .66, .38 and 2.49 respectively. Feeding the diet with .38 mg of Cu per day was associated with a significant decrease in proliferation of peripheral blood mononuclear cells cultured in a variety of antigens and an increase in the percentage of circulating B cells. There was no effect on the concentration of serum interleukin II receptor, percentage of peripheral monocytes, neutrophils and T cell subsets or neutrophil phagocytic activity. When feeding 2.49 mg of copper per day for 24 days prevented decreases in indexes affected by the low copper diet it did not restore them to their prestudy levels even though plasma copper and ceruloplasmin concentrations were restored to normal. It is possible that other dietary or known dietary factors cause these changes. It is possible that the duration of the high copper intake of 2.49 mg per day for 24 days was not enough to reverse the effects of the low copper intake. Further studies feeding this amount for longer periods than 24 days and/or feeding amounts greater than 2.49 mg of copper per day are needed to clarify the effects of dietary copper on human immune response. 22975 [imm] This study evaluated 14 saphenous vein grafts from patients who needed a second revascularization procedure. Dermatan sulfate is the main glycosaminoglycan seen in both normal saphenous veins and saphenous vein grafts. These tissues also contain chondroitin sulfate and heparin sulfate. Even though the total amount of glycosaminoglycans decreased in the grafts compared with the normal saphenous veins, the grafts showed an increase in the relative amount of dermatan sulfate and chondroitin sulfate. Heparan sulfate was decreased, compared with normal controls. These findings suggest that the involvement of blood vessel glycosaminoglycans are involved in the process of atherosclerosis. This suggests that vein grafts, with regards to glycosaminoglycans, appear to be effected by a similar mechanism to arteries in the atherosclerotic process. 22041 [car] Twenty patients with long term sporadic Alzheimer's disease received vitamin supplementation of iron, B6 and coenzyme Q10. There was a significant improvement in a variety of mental and functional tests at one year. It is believed that coenzyme Q10 might reduce the free radicals formed by iron, and that B6 plays a role in neurotransmitter synthesis. The combination of these 3 may have a positive effect on reducing the signs and symptoms of Alzheimer's disease. 21436 [ger, neu, nut, psy] One hundred and five Finnish national-level female squash players were compared to 50 healthy controls for arm bone mineral density. Compared to the controls the players had a significantly larger side to side difference in bone mineral density at every site. Among players, the differences in bone mineral content were significant. The differences were 2 to 4 times greater in players who had started their playing careers before or at menarche than in those who started more than 15 years after menarche. The authors conclude that bones of the playing extremity from tennis or squash clearly benefited from these sports which increased their mineral mass. The benefit of playing is about 2 times greater in females playing at or before menarche rather than after. Menarche in the completion of longitudinal growth are the first signs that bone mass is stopping. Two years after these developmental changes the expected increase in bone mass is only marginal. Our study provides evidence that physical activity during the pubescent is crucial for maximizing bone loss. This data does not ignore the potential for exercise-induced bone gain in adults but clearly shows that the benefit is about 2 times greater if the woman starts her playing career at or before menarche than after menarche. 22782 [end, ort] Forty healthy premenopausal women with autoimmune thyroiditis taking either physiological or suppressive doses of L-thyroxine were compared with premenopausal volunteers with no history of thyroid function. Twenty-eight patients were followed up more than 1 year later. In all the subjects, bone mineral density, serum osteocalcin, parathyroid hormone and vitamin D, and urinary cross-link excretion did not differ between the 2 groups. The authors did not find any effect of persistent historical TSH suppression on current bone mass. The cross sectional and longitudinal data suggests that a high daily dose of thyroxine in relationship to the patient's body weight might adversely affect bone mass, especially at the hip. These findings do support the possibility that excess exogenous thyroxine might deplete skeletal sites such as the femoral neck rich in cortical bone. 21644 [end, ort] Ten unselected consecutive patients between 25 to 58 years of age with child's grade C cirrhosis, who were being assessed for liver transplantation, were evaluated for whole blood manganese concentrations. In these patients with liver cirrhosis there was a significantly increased level of whole blood manganese 34. ug/L versus 10.3 ug/L in the controls. Pallidal signal intensity correlated with blood manganese. Brain tissue samples showed the highest manganese concentrations in the caudate nucleus followed by the quadrigeminal plate and globus pallidus. Manganese accumulates within the basal ganglia and liver ganglia in liver cirrhosis. The similarities between manganese neurotoxicity and chronic hepatic encephalopathy suggested this metal may play a role in the pathogenesis of chronic hepatic encephalopathy. Chelating agents may prove to be a therapeutic option to prevent or reverse this neuropsychiatric syndrome. 22961 [neu, tox] Nitric oxide is a second messenger important in the control of resting blood pressure. Derangement of the L-arginine:nitric oxide pathway may cause certain types of hypertension specifically salt-sensitive, low-renin hypertension. The use of organic nitrates and nitroprusside produced vasorelaxation by the same guanylate cyclase system used by endogenous nitric oxide. It is noted that nitric oxide is a vasodilator that plays a major role in blood pressure regulation. Nitric oxide is produced endogenously by a family of nitric oxide synthases that utilize L-arginine as a substrate. 22707 [car] Malnutrition is associated with mucosal atrophy and poor intestinal absorption. Malnutrition may effect cytokine production and cytokines produced in response to infection, interleukin-1, interleukin-6 and tumor necrosis factor can be a direct cause of malnutrition and wasting. Malnutrition is an integral part of infections including AIDS because the cytokine network interacts critically with the host defense system which may be altered by nutritional status. Cytokine patterns thought to mediate host defense in the peripheral blood are characteristic of an inflammatory response in the gastrointestinal tract and may precipitate altered nutritional metabolism possibly leading to malnutrition and impaired immune functioning in the host. Inflammatory reactions can increase tumor necrosis factor production in conjunction with regional HIV infection may reduce gastrointestinal absorption. It is noted that the antioxidants C, E and beta-carotene play important antioxidant roles within cell membranes. Copper, zinc and manganese are important in superoxide dismutase and selenium in glutathione peroxidase which help reduce oxygen species within cells. 22489 [gas, imm] In a randomized controlled trial vitamin A supplementation in 1,455 children between 6 and 59 months living in rural Northern Ghana were given 4 monthly oral doses of either 60 mg 200,000 I.U. of retinol or 30 mg for children between 6 and 11 months of age or 100,000 I.U. of retinyl palmitate plus 40 I.U. of vitamin E or placebo. The trial ran over 1 year. There was a tendency for vitamin A supplemented children but not placebo children to have elevated acute phase proteins in association with vomiting or severe diarrhea. The unsupplemented children failed to mount an acute phase response which may have contributed to their increased morbidity from gastrointestinal symptoms. 22972 [inf] A recent study has found that the proportion of children with deficient intakes which is less than 70% of the RDA of nutrients are significantly higher than proportions of non-poor children on 10 of 16 nutrients tested. These findings suggest that large numbers of American children are not receiving adequate nutrients and that poor children are at greater risk of inadequate nutrient intake than non-poor children. These findings are in accordance with other information which suggests that food insecurity and hunger are widespread problems among children who are poor. These findings are consistent with the National Health and Nutrition Examination Survey II which found that for children ages 3 to 5 there was a higher proportion of poor children with intakes less than 50% of the RDA for 3 nutrients. 22472 [nut] In one family a pet dog had persistent vomiting and weight loss after the exterior renovation of the home. He was admitted to a veterinary hospital and the diagnosis of lead poisoning was made. The dog recovered after chelation therapy but was readmitted 9 months later with a blood lead level at 120 ug per dl. Testing a 1- and 3-year-old who were asymptomatic in the same family revealed blood lead levels of 48 and 37 ug per dl. Exposure was traced to the ingestion of lead chips found in the yard. The one-year-old child received chelation therapy with edetate calcium disodium and penicillamine. Blood lead levels fell spontaneously in the other child after relocating to deleaded housing. In a second family a pet cat developed vomiting, somnolence and ataxia one month after the exterior renovation of the neighboring house. The cat was found to have lead poisoning and underwent chelation therapy. An asymptomatic 2-year-old in that family was found to have a lead level of 24 ug per dl. The child is being monitored without chelation therapy. Pets may serve to identify lead-contaminating environments. These cases suggest that lead screening is appropriate in families whose pets have had cases of lead poisoning. 21495 [env, tox] This study evaluated 58 patients needing hemodynamic monitoring due to septic shock. These patients were evaluated 72 hours after the onset of sepsis. They received either 150 mg/kg of intravenous N- acetylcysteine or a placebo over a 15 minute period, then a continuous infusion of 12.5 mg/hour of N-acetylcysteine or a placebo over approximately 90 minutes. Forty-five percent of the patients responded to the N-acetylcysteine infusion. The N- acetylcysteine responders also showed an increase in gastric intramucosal pH, a decrease in veno-atrial Pco2 and an increase in oxygen delivery, cardiac index, stroke index, and left ventricular stroke work index, as well as a significant decrease in systemic vascular resistance in comparison to baseline. N-acetylcysteine nonresponders and the placebo group had no significant changes in any of these variables. The N-acetylcysteine responders had a 69% survival rate compared to 19% of nonresponders. N-acetylcysteine provided a transient improvement in tissue oxygenation in about half of the septic shock patients, as indicated by an increased V02 and gastric intramucosal pH and a decrease in veno-arterial C02. The fact that there is a varying response to N-acetylcysteine suggests that in some patients sepsis irreversibly damages the microvasculature to the extent that N-acetylcysteine has no effect. Further investigation is needed to determine whether N- acetylcysteine can be effective in the treatment of sepsis or whether the N-acetylcysteine challenge was merely diagnostic. 21654 [cri] This study evaluated 107 consecutive patients undergoing coronary angioplasty and their relationship to clotting factors. Fibrinogen, which was measured within 6 months of the follow-up, was significantly increased in all restenosis groups. Patients with a fibrinogen concentration than 3.5 g/L at follow-up had a higher restenosis rate than patients with a concentration of less than 3.5 g/L. There was a significant correlation between fibrinogen level and angiographic loss index. Multivariate analysis confirmed that fibrinogen level predicted restenosis with all definitions. An elevated fibrinogen level during the follow-up is a strong biochemical predictor of restenosis. Fibrinogen should be considered at least an independent marker of restenosis and perhaps a common risk factor for both spontaneous coronary atherosclerosis and post angioplasty restenosis which is an accelerated form of atherosclerosis. 22786 [car] Participants in this survey included 3,115 residents and 1,920 practicing physicians in pediatrics, obstetrics/gynecology, and family medicine. The overall response rate was 68%. Less than 50% of the residents chose appropriate clinical management for a breast-fed jaundiced infant or a breast abscess. Practicing physicians performed slightly better, but still more than 30% chose incorrect advice for mothers with low milk supply. Most of the breast feeding instruction given by residents was from didactic lecture, not patient experience. Only 55% of senior residents recalled even one incidence of precepting related to breast-feeding, and less than 20% had shown breast-feeding techniques at least five times during their residency. More than 50% of all practicing physicians rated their residency training on breast-feeding counseling as inadequate. Physician involvement in breast feeding promotion was endorsed by 90% of the respondents, yet only half rated themselves as effective in counseling breast-feeding patients. The authors concluded that in this review of residents and practicing physicians in three specialties, physicians were ill-prepared to counsel breast- feeding mothers. 21780 [gyn, nut, ped] For 4 weeks a dose of 50 gm flaxseed was given to 10 healthy, young adults mean age of 25 with a body mass index of 21.7 kg/m2. During the flaxseed consumption there was a significant increase in adipose alpha-linolenic acid. Omega-3 fatty acids were increased in plasma lipids. Plasma LDL cholesterol was reduced by up to 8% and total urinary lignan excretion was increased more than 5-fold. Muffins containing 25 gm of flaxseed did not differ significantly from control muffins in their content of thiobarbituric acid- reactive substances and alpha-linolenate. Alpha-linolenic acid in the muffins was not significantly reduced by baking. Antioxidant vitamins and lipid hydroperoxides in the plasma were not significantly affected by flaxseed supplementation. Bowel movements per week increased by 30% while flaxseed was being consumed. In conclusion, flaxseed supplementation in healthy adults improves bowel movements, modestly reduces LDL cholesterol, raises polyunsaturated fatty acids in the plasma and adipose and markedly increases urinary lignan excretion. 21627 [car, gas, nut] This is a case report of a 58-year-old white male paraplegic who required the use of a condom catheter for bladder incontinence following an L1 spinal cord injury in 1967. For 25 years he utilized condom catheters derived from rubber tubing, elastic bandages, silicone adhesive and nonlubricated rubber condoms before experiencing recurrent blisters and sloughing of the epidermal layer on the penile shaft. The patient had known allergies to adhesive bandages but no other history of sensitivities to latex or rubber. The patient is using a silicone condom with no latex or other components. The dermatitis has resolved. 22294 [der] This study evaluated over 126,000 discharge summaries from January 1987 to July 1993 for the relationship between acetaminophen ingestion and hepatotoxicity. Forty-nine patients with acetaminophen hepatotoxicity were identified with an aspartate aminotransferase level greater than 1,000 U/L. Twenty-one patients, or 43%, took acetaminophen for therapeutic purposes. All the patients with hepatotoxicity took more than the recommended limit of 4 gm per day. It is noted that recent fasting was more common than recent alcohol use among those who developed hepatotoxicity after a dose of 4-10 gm of acetaminophen per day. In those who took over 10 gm per day, recent alcohol use was more common than those who took between 4-10 gm per day. Acetaminophen-induced hepatotoxicity after an overdose appears to be enhanced by fasting in addition to alcohol ingestion. Fasting may be an important, predisposing factor for acetaminophen toxicity in patients who consume between 4 and 10 gm of acetaminophen within 24 hours. 21523 [gas, gen] Nutrition screening was done for over 1,100 Alaskan Native residents age 20 years or older. Two hundred and two of these subjects had an oral glucose tolerance test. Athabascan Indians had twice the rate of non insulin dependent diabetes mellitus as the Yup'ik Eskimos with a significantly higher frequency of nonindigenous food intake, plus a lower frequency of indigenous carbohydrate and fat intake. Those subjects less than 30 years of age consumed more nonindigenous protein and fat and low-nutrient- density carbohydrates than those greater than 60 years old. Those who had glucose intolerance reported a greater consumption of nonindigenous protein and less seal oil. The incidence of being overweight was significantly higher than it was 25 years ago. Participants with glucose intolerance were significantly more overweight. The authors conclude that increased frequency of nonindigenous protein, low nutrient-density-carbohydrate and fat intake with less indigenous carbohydrate and fat consumption was found in subjects less than or equal to 30 years of age and were associated with a higher rate of non insulin dependent diabetes mellitus in Athabascan Indians. 22571 [end] This was a 1 year prospective study evaluating 266 female and 59 male community dwelling volunteers ages 60 to 93 years who had fallen at least once during the previous year. Frail individuals were more than twice as likely to fall as vigorous individuals. Falls were not strongly associated with the presence of home hazards. Vigorous older persons living with more hazards were more likely to fall than vigorous individuals with lesser hazards. In frail individuals living with more home hazards was not associated with an increased likelihood of falls. Vigorous older individuals should not overlook fall prevention projects. 22748 [ger, ost] Healthy individuals were given 2 gm of vitamin C per day for 2 months. Vitamin C increased in the blood while whole blood iron, hemoglobin and serum ceruloplasmin levels significantly increased at the end of the first month, but decreased to control levels at the end of the 2nd month. With vitamin C supplementation in guinea pigs, liver ferritin iron, liver copper, serum copper and serum ceruloplasmin levels significantly decreased. There was no significant change in hemosiderin iron while blood ascorbic acid significantly increased at the end of the 2 month period. There was no significant change in serum iron and hematocrit levels. These results suggest that vitamin C has antagonistic effects on copper metabolism in guinea pigs but not in humans either on copper or iron metabolisms. 22004 [nut] This study evaluated Danish women consuming 70 gm of raw onion or 5 gm of raw ginger daily for a period of 7 days. Tx B2 determination showed an increase from 910 to 1005 pmol/ml in the serum and ginger consumption resulted in a reduction of 782 to 498 pmol/ml in the serum. Onion consumption can reduce platelet activity. Onion extract has been shown to be useful in treatment of hypertension and hyperlipidemia. The results of this study show that ginger is effective in inhibiting eicosanoid biosynthesis in vivo. Ginger consumption may provide relief in rheumatoid arthritis by reducing pain and improving movement of joints in patients suffering from arthritis. Ginger may be doing so by being a dual inhibitor of cyclooxygenase and lipoxygenase pathways thereby reducing the amounts of prostaglandins and leukotrienes. 22132 [car, rhe] This study evaluated 94 patients at entry and at 5 year follow-up for the relationship between hyaluronic acid and osteoarthritis of the knee. Hyaluronic acid levels were significantly related to disease duration, minimum joint space and previous surgery at entry. Those who progressed with the disease had significantly higher levels of hyaluronic acid at baseline compared with those whose disease had not progressed. This data suggests that hyaluronic acid levels predict disease outcome and osteoarthritis of the knee and confirm that a serum level of keratin sulfate is not a useful prognostic marker for osteoarthritis. 22658 [art] In evaluating 11 normal-weight bulimia nervosa females there was significantly higher serum levels of free testosterone than age- matched controls. The possibility that women with higher androgen levels are more susceptible to disorders characterized by poor impulse control, such as bulimia nervosa and PMS, needs further evaluation. It is noted that a report of women suffering from obsessive-compulsive disorder, which is a disorder of impaired impulse control, responded to a serotonin reuptake inhibitor. This condition may also be treated with the testosterone antagonist cyproterone acetate. 21357 [end, gyn, nut] This study evaluated 610 patients who underwent coronary artery bypass and who were followed through their first postoperative year. Serum levels of lipoprotein(a) and homocysteine in patients with occluded internal mammary artery grafts were not significantly different from levels in those with open intermammary grafts. Serum lipoprotein(a) levels in patients with greater than or equal to one occluded vein graft were not significantly different from those in patients with all vein grafts open. The number of patients with vein graft occlusions was higher in the lowest quartile of lipoprotein(a) than in the upper three quartiles. There appears to be no association between preoperative serum lipoprotein(a) or homocysteine levels and the frequency of graft occlusion at one year. 21483 [car] This nation has a series of health objectives that they wish to achieve by the year 2,000. To achieve these goals physicians will have to make a very significant commitment. Physicians will have to not only provide the preventive services but also support states and local health departments in establishing these public health policies. Preventive services will include screening for disease in patients without symptoms, counseling patients about lifestyle and providing immunizations or chemoprophylaxis to prevent disease will be part of the physician's job. Physicians at present are not providing all the prevention that patients need or want. Preventive services are provided less often than are recommended and that people expect. The reasons for this include lack of thorough training on how to provide preventive services on clear standards of preventive care, organizational barriers to delivery of preventive services, inadequate reimbursement for preventive services and the patient's lack of access to these services. The current paradigm of medical education at both the predoctoral and post doctoral levels focuses on disease rather than health. Physicians are not trained to ask questions about disease risk nor are they trained to intervene to improve health behaviors. To enhance the level of preventive services by physicians, there needs to be a greater emphasis on preventive medicine and health counseling in medical schools and residency curriculum. The need for standards of care in preventive medicine have been finally recognized. Preventive services are slowly being recognized by payers at all levels. At first to improve the quality of health care provided by health plans are increasingly focused on how physicians are ensuring that their patients receive needed preventive services. Therapeutic services are only required to be safe and effective for reimbursement purposes. Preventive services must be safe and effective and have a positive cost benefit. This is a double standard. For the United States to enjoy the best health status, physicians need to "nurture, advocate for, and support a neglected portion of the health care system - public health. We must not forget that the core of public health functions have been responsible for much of the improvement of health status in the last 100 years. We must ensure that this core health system continues to provide its much needed services". And secondly, physicians need to provide clinical services to their patients. 22177 [med] This study evaluated wintertime 25-hydroxyvitamin D concentrations in 824 elderly people from 11 European countries. Thirty-six percent of the men and 47% of the women had 25-hydroxyvitamin D concentrations below 30 nmol/l. Users of the vitamin D supplements and/or sunlamps had higher 25-hydroxyvitamin D levels than nonusers. The lowest mean 25-hydroxyvitamin D concentrations were seen in Southern European countries. Low 25-hydroxyvitamin D concentrations could be explained by the attitudes towards sunlight exposure and factors of physical health status. Problems with daily living activities and wearing clothes with long sleeves during periods of sunshine were strong indicators of low wintertime vitamin serum 25-hydroxyvitamin D concentrations. This study shows that free living elderly Europeans regardless of their geographical location are at substantial risk for inadequate vitamin D status during winter. Dietary enrichment or supplementation should be seriously considered during the winter months. 22900 [ger, neu] This study evaluated oral arginine supplementation utilizing 30 g of arginine aspartate (net free arginine intake 17 g/d) in 30 subjects or a placebo in 15 subjects for 14 days. The arginine aspartate was dissolved in 60 ml of an aromatic syrup. Two weeks of arginine supplementation lead to an elevation of serum insulin-like growth factor concentrations and improved positive nitrogen balance compared to controls. The arginine supplemented group showed a decreased total serum cholesterol with a reduction in the low density lipoprotein but not the high density lipoprotein fraction which resulted in an increase in the low to high density lipoprotein fraction. No other adverse consequences were noted. The data suggests that oral arginine supplementation may be used safely in elderly humans. Recent data suggests that arginine supplementation may be beneficial in enhancing immune response in trauma and cancer patients and may also promote wound healing. This data showed that pharmacologic doses of arginine had no side effects in the elderly and maintained positive nitrogen balance while reducing cholesterol levels. 22617 [can, car, cri, ger, imm] This study evaluated the association between breast cancer and dietary intake in 2 Chinese populations who are at low risk for breast cancer. These populations have 1/5th the rate of breast cancer than U.S. white women. There were 2 case-controlled studies. In Shanghai 534 women between 20 and 69 years of age with confirmed breast cancer were recruited and in Tianjin there was 300 women between 20 and 55 years of age with confirmed breast cancer. Overall, all the components of dietary fat including saturated, monounsaturated and polyunsaturated fats showed a modest, nonsignificant association with breast cancer after adjusting for energy intake and non-dietary factors for breast cancer. The intake of crude fiber, carotene and vitamin C had a strong significant inverse association with breast cancer risk. The effect was closely associated with the intake of green vegetables. Vitamin E intake was unrelated to breast cancer risk in Shanghai and Tianjin. Shanghai women in the lowest intake of crude fiber intake and the highest tertile of fat intake had a 2.9-fold increased risk for breast cancer relative to those in the highest tertile of crude fiber intake and the lowest tertile of fat intake. This data suggests a strong protective effect against breast cancer development with intakes of food rich in fiber, vitamin C and carotene. This data did not support the hypothesis that a high intake of soy protein protects against breast cancer. 22903 [can] This study evaluated 48 children admitted consecutively for surgical correction of congenital heart disease and found a marked degree of under-nutrition evident in all children. Fifty- two percent had weight less than the third centile, 37% were below the third centile for height and 12.5% were below the third centile for triceps skin fold thickness and 18.8% for subscapular skin fold thickness. Mid-arm circumference and arm muscle circumferences were below the fifth centile in 20.1% and 16.7% of the children, respectively. Five or more of the 29 biochemical and haematological measurements were abnormal in 83.3% of the patients. Ten or more were abnormal in 12.5% of the patients. The authors conclude that children with congenital heart disease are frequently undernourished, regardless of what is the exact nature of the cardiac defect and the presence or absence of cyanosis, a sign of lack of oxygen. 22040 [car] This study evaluated 16 patients who received 50 to 100 mg of beta-carotene on alternate days for 3 weeks following a week-long loading dose of 100 mg per day. Plasma beta-carotene levels rose 5.5-fold while LDL beta-carotene levels rose 8.5-fold. Oxidation of LDL was not significantly delayed after in vivo supplementation with beta-carotene compared with baseline. The lag phase was 75 minutes at baseline and 83 minutes after supplementation. With the oxidation of LDL by Cu2+, the lag phase was 172 at baseline and decreased to 130 after supplementation. There was not a protective effect against copper-induced oxidation when beta-carotene was added to the LDL group in vitro. Supplementation of plasma with B-carotene in vitro prior to LDL isolation did not enhance LDL's resistance to copper in spite of a 5-fold increase in LDL beta-carotene levels over the control vehicle. These results suggest that supplementation with beta-carotene in vivo or in vitro does not enhance the protection of LDL against metal ion-dependent and ion-independent oxidation. 21761 [car] This study evaluated 15 nutrients in 351 low to middle class parents and their preschool children. Boys and anglo Americans had higher total nutrient intake than girls and Mexican-Americans respectively. Mexican-Americans had higher nutrient intakes per energy intake which indicates a micronutrient dense diet. Nutrients most likely to be inadequate included iron, zinc, vitamin D, vitamin C and niacin. Mexican-American girls had significantly lower calcium intakes than other gender ethnic groups. 22737 [nut] Genuine food intolerance can be due to a variety of mechanisms which include enzyme deficiency, pharmacological reaction, a toxic effect or, an immunologic reaction would be more specifically classified as a food allergy. The relationship to food and behavior is a noteworthy topic among the news media. Foods can have pharmacological effects. Caffeine for example in coffee and other foods can increase wakefulness and concentration but can also cause irritability. The peptides in milk and wheat have exorphin-like activity. Amino acids such as tryptophan in foods are the precursor to vaso-active mediators such as serotonin and can act as precursors for neurotransmitters. Food containing high concentrations of these amino acids may affect behavior, mood and appetite. Foods high in certain additives such as tartrazine have been shown to effect basophil's histamine release. It is not surprising that a high food additive- containing diet might accentuate hyperactive behavior by direct pharmacologic mechanism. The standard for diagnosis of food intolerance is the double-blind food challenge. Few clinics have the experience or the time to devote to this "painstaking" diagnostic procedure. In 1 study of 104 patients with severe migraines 38% improvement on diet, 26 reacted on open challenge with food but only 15% had reproducible symptoms on double-blind challenge. In 1 study 59 of 78 children referred to a diet clinic with hyperactive behavior improved on a few food diet, 19 subsequently had a double-blind challenge with the offending foods and a crossover challenge and clear differences were seen in 14 children with significant difference between active and placebo challenges. Whether total exclusion of a food is necessary or whether only a reduction of the pharmacologically active ingredients to reduce the reaction to food and improve behavior is not known. It is also important to note that in behavior problems in children it is natural for a parent to be lead to the believe that a particular symptom is due to a food which is an extrinsic factor versus some other psychosocial reason. The author concludes by this quote: "There is an association between certain foods and hyperkinetic disorders, but only in the minority of affected children". Still much work is needed to define the association between behavior, food and dietary modification. Individuals with genuine food-associated behavior should be evaluated to identify the underlying pathophysiological mechanisms which might improve the diagnosis and management of this in the future. 22932 [all, psy] Thirty-three individuals in 4 different studies had a 2 to 3-fold higher absorption from white wine containing a low concentration of polyphenols than from 2 red wines containing 10-fold higher concentrations of polyphenols. When the alcohol concentration was reduced there was a significant, 28% decrease in non-heme iron absorption with red wine but no effect with the white wine. The inhibitory effect of red wines with reduced alcohol content was about 2-fold greater when they were consumed with a small bread roll than taken without food. This data suggests that the inhibitory effect of phenolic compounds in red wine is unlikely to effect iron balance significantly. A lower incidence of coronary heart disease in wine drinkers in France consuming a high fat diet was recently reported. It is possible that phenolic compounds in red wine produce an inhibition of iron absorption and thereby protect against the development of increasing iron stores with age which may increase risk to cardiovascular disease. Modest inhibition of iron absorption for red wine seen in this study does not support this hypothesis. If there is a benefit in red wine intake in the prevention of ischemic heart disease it is probably due more to the antioxidant properties of red wine polyphenols. 22364 [car] Two hundred eight individuals who developed stomach cancer and 77 persons who developed lung cancer were evaluated. The average serum levels of selenium and zinc were slightly but not significantly lower among the cancer cases than the controls. The trends in the risk of cancer with decreasing serum levels were neither linear nor significant. Little or no excess risk of stomach cancer was observed among those with the lowest level of selenium or zinc. This data shows a slightly increased risk of lung cancer associated with lower levels of blood selenium, but suggests little association with either lung or stomach cancer across normal selenium and zinc ranges in this Japanese population. 22008 [can] This study evaluated 37 patients median age of 37 years with seasonal ataxic syndrome of unclear etiology in Western Nigeria. These individuals were of low socioeconomic status and were maintained on a monotonous diet of high carbohydrate meals with minimal protein supplementation. Prior to the onset of their disease, the patients consumed a stew containing the roasted larvae of Anaphe Venata, a seasonal protein supplement found in the area . These features were similar to those found in acute thiamine deficiency and support the possibility of acute thiamine deficiency in this Seasonal Ataxic Syndrome. This study indicates that Seasonal Ataxic Syndrome occurs exclusively in individuals of low socioeconomic status who consume monotonous diets of heavy carbohydrate meals. There is really no evidence of viral infection as the cause. The authors believe that this Seasonal Ataxic Syndrome is a variant of Wernicke's disease, in which patients become marginally thiamine deficient due to the monotonous type diet. Also, these foods contain thiamine-binding cyanogenetic glycosides which can exacerbate thiamine deficiency seasonally. The authors feel there is a need for entomochemical studies to determine the thiaminase activity of Anaphe venata larvae. 22021 [nut] This study evaluated the levels of plasma and milk vitamin E in women with insulin-dependent diabetes mellitus, women without insulin-dependent diabetes mellitus and healthy reference women. There was no difference between the groups for plasma vitamin E, which was in the normal range. Vitamin E (ug/g lipid) decreased by approximately 50% in all groups in 7 to 14 days. The trend for milk vitamin E was similar when expressed as ug/dl. Metabolic control of diabetes did not have a significant effect on mean milk or vitamin E concentrations. The results of this study showed that this group of women with insulin-dependent diabetes mellitus produced a milk with vitamin E content similar to the control and reference women. The authors conclude that the infant of a breast- feeding woman with insulin-dependent diabetes mellitus who was in good metabolic control during pregnancy and who receives good prenatal counseling is most likely to receive adequate vitamin E from the mother's milk. 22533 [gyn, ped, und] Out of a total of 5,280 students between 11 and 15 years of age celiac disease was diagnosed in 23 cases. Most of these cases were atypical or silent forms. The prevalence of undiagnosed celiac disease was 4.36 per 1,000 screened subjects and 5.03 per 1,000 in the general population. The ratio of known to undiagnosed cases of celiac diseases was 1 to 6.4. There is a high prevalence of undiagnosed celiac disease. Frequent problems found in celiac disease patients include iron deficiency, recurrent aphthous stomatitis, failure to thrive, irritability, recurrent abdominal pain, gluten free diet during infancy, and recurrent diarrhea. This Italian study shows that celiac disease is much more common than previously thought and that most cases remain undiagnosed unless actively identified through serological screening tests. 22718 [gas] In evaluating 72 exposed pottery workers to silica compared to 55 controls from the same socioeconomic background, average age of 35 years, it was found that mean pulmonary function values for men and women were significantly lower in even indirectly exposed pottery workers, compared to controls. These results suggest that silica dust is a risk factor for chronic airflow limitations and it is independent of radiographic changes. 22091 [pul] In 1981 it was estimated by Doll and Peto that of all cancer deaths in the United States 30% were due to tobacco, 3% to alcohol and 35% to diet and other causes. Twelve percent of lung cancers were not attributable to tobacco and dietary factors were implicated in the causation of cancer in tissues other than the gastrointestinal tract. Damage to cellular DNA not only occurs from environmental mutagens but also from the endogenous production of oxidants which damage DNA and other mechanisms related to the conversion of food, in particular fats to energy. Inflammation and the healing process can also result in damage. Dietary antioxidants have also been shown to prevent this oxidative cellular DNA damage; these include vitamin A, the carotene family, vitamin C, E and selenium. In reviewing approximately 200 published studies there was overwhelming evidence that the consumption of fruit and vegetables is associated with reduced cancer incidence. In relation to lung cancer, a protective effect was seen in 30 of 32 studies. Infrequent consumers of fruits and vegetables had, on the average, 2.2 times higher incidence of cancer than frequent consumers. Recently a study of Finnish male smokers found that vitamin E and/or beta-carotene supplementation up to 8 years did not reduce the risk of developing lung cancer. One explanation might be that supplementation by the administration of a single pulse dose of vitamin E and/or beta-carotene does not provide protection that the consumption of diets rich in fruits and vegetables and other antioxidants might. Secondly, the trial may have not lasted long enough or might have started too late in the carcinogenic process. Thirdly, in the case of vitamin E, the dose may have been too small. Despite the results of the Finnish trial it remains clear that in any realistic "pie chart" evaluation factors associated with lung cancer risk might include a portion relating to diet. Smokers tend to eat more fat and less antioxidants than nonsmokers. In the case of exposure to environmental tobacco smoke, the dose of smoked chemicals inhaled by nonsmokers are minute compared with those inhaled with active smokers. 21544 [can] This study evaluated 832 men between 45 and 65 years of age who were free from cardiovascular disease at baseline. There were 97 incident strokes upon follow-up. There was an age adjusted risk of stroke that decreased across increasing quintiles of servings per day of fruits and vegetables. The relative risk for all stroke was .78 for each increase of 3 servings per day. For complete stroke the relative risk was .74; for completed stroke of ischemic origin the relative risk was .76; and for a completed stroke of hemorrhagic origin the relative risk was .49. The authors conclude that intake of fruit and vegetables may be protective against stroke in men. The protective effect does not appear to be mediated through effects on blood pressure. Increasing the intake of fruits and vegetables may not only have a beneficial effect on the incidence of stroke, but other chronic diseases that are leading causes of morbidity and mortality in western societies. 22155 [car] This was a cost benefit analysis on fortifying grain with folic acid to prevent neural tube defects. It is probable that fortification would yield a net economic benefit. The best estimation of this benefit is 94 million dollars worth of low level fortification of 140 mcg per 100 gm of grain and 252 million with high level 350 mcg per 100 gm. The benefit to cost ratio is estimated to be at 4.3:1 for low level and 6.1:1 for high level fortification. By averting the cost of birth defects folic acid fortification of grain in the United States may result in a substantial economic benefit. The authors may have over estimated the net benefits of the cost of neurologic sequelae related to delayed diagnosis of vitamin B12 deficiency which has exceeded their projection. 22381 [nut] Twenty-four men undergoing coronary surgery participated in a randomized, controlled study. Twenty-eight gm of alpha- ketoglutarate were added to the blood cardioplegia for intermittent antegrade intracoronary perfusion in 13 cases. Alpha-ketoglutarate reduced the appearance in blood of the ischemic markers creatinine kinase MB and troponin T. These results suggest that alpha- ketoglutarate may attenuate ischemic injury, possibly secondary to enhanced myocardial oxidative capacity. Alpha-ketoglutarate may be a treatment in the prevention of heart failure in myocardial ischemia and trauma/sepsis. 21910 [car, sur] This study compared 1,768 women with breast cancer to 13,905 controls, most of whom were below 55 years of age. The relative risk of breast cancer for women who had ever used depot medroxyprogesterone was 1.1. There was no increased risk with the increasing duration of depot medroxyprogesterone use but the relative risk estimates were higher in certain subgroups of women. Women who had started using depot medroxyprogesterone within the previous 5 years were estimated to have a relative risk of 2.0. The increased risk of breast cancer seen in users could be due to enhanced detection of breast tumors in women using depot medroxyprogesterone or to the acceleration of the growth of pre-existing tumors. Women who had used depot medroxyprogesterone more than 5 years previously had no increased risk of breast cancer regardless of the duration of use. Depot medroxyprogesterone acetate has been now approved for marketing as a contraceptive agent in the United States even though there are still some unresolved issues regarding its relationship to the risk to breast cancer. 21962 [can] Lipoprotein (a) is an atherogenic lipoprotein that resembles LDL cholesterol but has an additional apoprotein (a). Lipoprotein (a) was evaluated in 203 Caucasian subjects with coronary artery disease and in 66 subjects without coronary artery disease. Lipoprotein (a) was elevated in coronary artery disease patients compared to subjects without coronary artery disease. There was no difference between patients that had myocardial infarction as a first sign of the disease and those who had only angina pectoris for 2 years. Plasma lipoprotein (a) levels were correlated with the extent of the disease. In those who had coronary artery disease lipoprotein (a) levels were higher in females. In a smaller group of 29 black subjects it was found that lipoprotein (a) was higher than in Caucasians but there was no difference between the subjects with and without coronary artery disease. The data here shows that lipoprotein (a) levels do not influence the clinical presentation of coronary artery disease. Lipoprotein (a) level were correlated with the extent of the disease. Lipoprotein (a) levels were higher in blacks than in Caucasians but in blacks lipoprotein (a) was not predictive of the disease. Smoking was the most important risk factor for the development of coronary artery disease followed by higher plasma apo (b) and lipoprotein (a) concentrations. 23024 [car] Fifty percent of 41 premenopausal women average age of 36.4 years received 25-hydroxy vitamin D at 20 mg per day for 34 days. Significantly more calcium was absorbed in the treatment group in the winter compared to summer months. There was a positive relationship between serum vitamin D, intestinal transit and urinary:creatinine ratio on calcium absorption. Vitamin D intestinal receptors and serum 1,25 (OH)2D levels influenced calcium absorption efficiency. 22684 [end] This study evaluated 202 patients who were given a brand of L- tryptophan (Optimax, Merck) over a 5 year period. Fourteen patients were noted to have clinical or laboratory findings suggestive of a diagnosis of eosinophilia-myalgia syndrome. However, the results of clinical examination and measurements of serum aldolase, total eosinophils and antinuclear antibodies did not support this diagnosis in these patients. A further study of 50 consecutive patients on L-tryptophan revealed that 5 had mild eosinophilia but none reached the criteria for eosinophilia-myalgia syndrome. In conclusion, in this study this one particular brand of L-tryptophan did not cause EMS syndrome in these 202 subjects. 21481 [all, imm, neu, nut] This article reviews the role of nutrition on gastrointestinal barrier function, especially in the intensive care unit. It is noted that the conditions in the intensive care unit can result in dysregulation of the epithelial barrier. This may lead to absorption of autotoxic macromolecules that are very large and diverse that normally stay in the gut lumen. This may cause significant immunologic problems. It may be that alterations in the intestinal microecology from such intensive care therapies as antibiotics, artificial nutrition and antacids in conjunction with altered mucosal immunity from drug immunosuppression and artificial nutrition may contribute to the systemic inflammatory response syndrome. Because the gastrointestinal tract contains more neutrophils and macrophages than all other organs combined, bacteria that trigger local cytokine release may significantly influence the systemic inflammatory response. Simple attachment of the microbe to the mucosal cellular target can result in activation of a signal transduction pathway in epithelial cells that activate the inflammatory cascade. Nutrition's effect on very early events in this process, specifically mucosal immunity and bacterial adherence, may give valuable insights into the mechanism by which diet influences the systemic inflammatory response. Pharmacologic and neuroendocrine mimicry may be needed for future nutritional formulations for the critically ill patient to reproduce the same immune responses that occur after eating normal food. 21605 [gas, imm] This study evaluated adipose tissue samples from 671 men with acute myocardial infarction aged 70 years or less, and 717 men without a history of acute myocardial infarction. There was no overall difference between cases and controls with respect to the proportion of adipose tissue C18:1 trans fatty acids. The risk of acute myocardial infarction did not significantly differ with the amount of trans fatty acid intake between the highest and lowest quartiles. After adjusting for certain variables, there tended to be an increased risk of acute myocardial infarction in the upper quartiles of the C18:1 trans fatty acids, though it was not statistically significant. The authors conclude that there are definitely considerable differences between countries in dietary intakes of trans fatty acids, but these do not suggest a major overall effect of C18:1 trans fatty acids on the risk of acute myocardial infarction. The authors cannot exclude the possibility that a very high intake of trans fatty acids may have a significant impact on acute myocardial infarction. Further evaluation is needed before strong recommendations are made. 21735 [car] Nine healthy individuals were supplemented with 316 mmol of magnesium per day for 30 days. Total magnesium levels did not change throughout the whole time of the experiment. Ionizable magnesium decreased during the first 10 days and bound magnesium tended to increase. Ionizable magnesium and not calcium was positively associated with parathyroid hormone. On day 0 calcium and ionized magnesium correlated with parathyroid levels. Both of these correlations vanished after magnesium supplementation. By keeping the levels of parathyroid hormone down, it ensures that supplemented magnesium enters the bone and is not liberated along with calcium by possibly increased parathyroid levels, triggered by high circulating magnesium concentrations. 22024 [nut] Epidemiologically there has been an association between thyroid cancer and seafood consumption. Fish consumption can increase the levels of the long chain fatty acids, eicosapentaenoic acid and docosahexaenoic acid. This study evaluated 74 cases of thyroid cancer compared to 221 matched controls. There was an inverse relation between the sum of arachidonic acid and DHA serum concentrations and thyroid cancer risks. In this study high EPA to arachidonic acid ratios, indicating the consumption of fish fat, were not associated with increased thyroid cancer risk. This data suggests that the association between seafood consumption and increased thyroid cancer risk is probably not related to marine fatty acid consumption. 21492 [can] This study evaluated 272 men and women with chronic renal failure who were compared to 272 controls. There was a significant increased risk of chronic renal failure found for exposure to lead, copper, chromium, tin, mercury, welding fumes, silicon containing compounds, grain dust and oxygenated hydrocarbons. Occupational exposures were high among patients with diabetic nephropathy. This data confirms that additional occupational exposures may be important in the development of chronic renal failure. The role of grain dust and the association between the exposure and diabetic nephropathy warrant further study. 22578 [nep] A physician utilizes, in acute otitis media with intense pain in small children, a 2 ml plain 2% Lidocaine solution plus 1 ml of 4 mg per ml of Decadron (dexamethasone) in the same syringe. After removing the needle, the ear is injected with this substance to fill the auditory canal and the opening is plugged with cotton balls. In most cases a child quickly quiets down and the remainder of the examination is much more peaceful. This helps in gratitude from the patient and the office is much quieter. 22423 [oto] In a randomized controlled trial vitamin A supplementation in 1,455 children between 6 and 59 months living in rural Northern Ghana were given 4 monthly oral doses of either 60 mg 200,000 I.U. of retinol or 30 mg for children between 6 and 11 months of age or 100,000 I.U. of retinyl palmitate plus 40 I.U. of vitamin E or placebo. The trial ran over 1 year. There was a tendency for vitamin A supplemented children but not placebo children to have elevated acute phase proteins in association with vomiting or severe diarrhea. The unsupplemented children failed to mount an acute phase response which may have contributed to their increased morbidity from gastrointestinal symptoms. 22972 [inf] Epidemiologic data states that a high intake of nitrates and nitrosyl compounds, early introduction of cow's milk into the diet, and a short duration or an absence of breast feeding increases the risk of insulin dependent diabetes mellitus. Studies in experimental animals show that cow's milk and soy protein may be diabetogenic. There is interest in the effects of free radical scavengers, such as niacin (vitamin B3) and natural and synthetic antioxidants, on insulin dependent diabetes mellitus. Abdominal obesity is a high risk factor for noninsulin dependent diabetes. Weight management is very important in this group of subjects. 21565 [end] This is an extensive review article on the role of essential fatty acids. In 1956 Sinclair suggested that abnormalities of essential fatty acid metabolism may be underlying factors in many of the degenerative diseases of western society, including cardiovascular disease, cancer and inflammatory disorders. Recent evidence suggests the role of essential fatty acids in cancer, vascular disease, diabetic complications and inflammatory disorders such as arthritis and atopic eczema. In research dating to the 1930's, it was noted that 1 or 2 gm per day of linoleic acid was adequate to control the skin lesions of essential fatty acid deficiency whereas 30 to 60 gm per day of linoleic acid were required to have beneficial effects in atopic eczema. Essential fatty acids were, for almost 20 years, the mainstay of treatment, then fell into disuse with the introduction of topical steroids. There does not appear to be a dietary deficiency in atopic eczema. However, all the metabolites of linoleic acid including gamma-linolenic acid (GLA) dihomogamma-linolenic acid (DGLA) and arachidonic acid (AA) are all reduced. This suggests a block in the conversion of linoleic acid to gamma-linolenic acid. Evening primrose oil (a source of gamma-linolenic acid) at a few grams per day has shown significant improvement in skin disorders and itch compared to placebo. Toxicity from other medications can be reduced. Diabetes has an effect on blocking delta 6 desaturase and delta 5 desaturase enzymes. In eczema, GLA and DGLA tend to be reduced more than arachidonic acid. They all may be lowered in diabetes. Very large doses of linoleic acid have been shown to reduce by two thirds the risk of heart and eye disease over a period of about 6 years. The administration of gamma-linolenic acid from evening primrose oil (EPO) has been shown to reverse and treat diabetic neuropathies in animal models. Double-blind, placebo-controlled trials in humans with diabetic nerve damage have shown that EPO can stop or reverse nerve damage in human diabetics. Animal models have shown that trans fatty acids inhibit the conversion of linoleic acid to its metabolites. There is now strong evidence from a large amount of research that trans fatty acids are likely to evoke cardiovascular disease. In treatment, it is important to give both omega-6 and omega-3 fatty acids. Large amounts of omega-3 fatty acids, when given alone, have the effect of depleting omega-6 fatty acids. This researcher says that the first cardiovascular study which provides omega-6 and omega-3 fatty acids beyond the rate limiting 6- desaturation step has shown a 3-fold reduction in reocclusion after human femoral arteries are open by balloon angioplasty. In a wide range of animal models GLA and DGLA of the n-6 series, and EPA of the n-3 series, are antiinflammatory due to stimulation of antiinflammatory prostaglandins. Both omega-3 and omega-6 fatty acids are probably needed for best results. There is evidence that cancer cells are depleted of essential fatty acids. Oxygenated metabolites of essential fatty acids are produced either by cyclooxygenase or lipoxygenase enzymes and involved in normal control of cell division. Providing essential fatty acids to cancer cells beyond the 6-desaturation step, which appears to be slow in many cancer cells, might control cancer cell division. In vitro and animal evidence has now shown this consistently. Supplementation with GLA, DGLA and EPA are able to kill all human cancer cell lines tested to date at concentrations which do not harm normal cells. For success in utilizing essential fatty acids in cancer, doses must be high and the cancer cells must be exposed to essential fatty acids for an extended period of time. IV administration of the salts of GLA has been developed. The lithium salt has been found to be beneficial due to its reduced toxicity and ability to be easily monitored. In over 30 patients with inoperable pancreatic cancer, and in smaller numbers with terminal breast and colon cancer, there have been some dramatic dose- dependent survival-extending responses. Pancreatic cancer is generally inoperable and no other treatment is given other than radiation. In various studies, the mean duration of survival after the diagnosis has been 80 to 120 days. With regards to GLA supplementation, the mean survival at the highest dose is now 300 days. This constitutes an approximate 3-fold extension of life without side effects. 21515 [all, can, car, der, end, inf] This commentary in support of natural family planning methods is considerably different than the "rhythm method" or the Roman Roulette approach. In a multi-center trial of the ovulation method of NFP that was undertaken between 1975 and 1979 one of the authors was a statistician. The main conclusions drawn from this study were that: A. Irrespective of cultural, educational, or economic background, over 95% of fertile women can, and are willing to, recognize the mucus signs of fertility; B. In this fertile group of women having regular intercourse without the use of barrier or chemical methods the fertility rate was 22.6 pregnancies per 100 women years; C. The preovulatory and postovulatory days designated by the ovulation method of NFP Rules as infertile were indeed infertile as the pregnancies in this phase were 4 per 1,000 acts of intercourse; and D. The designated fertile phase was indeed fertile, as intercourse during this phase resulted in conception with increasing frequency the nearer to ovulation the intercourse occurred which was 2 pregnancies for every 3 acts of intercourse on peak days of the mucus sign. The mucus changes to a more stretchy clear substance during the time of ovulation to enhance the viability of the sperm. The authors reviewed total pregnancy rates of natural family planning studies conducted in the 1990s which included broad spectrum of cultures. Three studies with results greater than 5 were all trials of atypical NFP approaches or teaching methods. The results can be compared with reported pregnancy rates of between .18 and 3.6 for artificial contraceptive methods in well motivated couples. NFP is the only method that empowers a couple to control their own fertility irrespective of economic status and independently of distributors of pills and condoms. Natural family planning allows couples to avoid or achieve pregnancy. Those wishing to achieve pregnancy will have extremely high pregnancy rates while those strongly motivated to avoid pregnancy will have extremely low pregnancy rates. A criticism of natural family planning is that the periods of abstinence are detrimental to the marital relationship and the family. It has not turned out since the advent of oral contraceptives that marriages, families, couples and children have benefit. It is noted that at the same time the pill has been around there has been a massive increase in marital and family breakdown. This is not a proven link, but some believe that the availability of uninterrupted sexual intercourse is something that is an unrealistic expectation in marriage and sets the course for the breakdown of marriage. NFP takes understanding and cooperation between the 2 married parties. There needs to be mutual discipline in NFP which can foster marital harmony and enhance relationship. Women note that in the times of avoidance of sexual intercourse there can be an enhanced expression of non-genital physical love which is something that has been longed for and helps their sexual responsiveness. The authors have suggested that there is a monthly honeymoon period which occurs at the resumption after the fertile phase enhances the sexual relationship. Some feel that natural family planning might be a partial solution to the sexual revolution of the last 20 or 30 years which has caused in some individuals, marital and family breakdown on a massive scale and at a vast cost. The authors feel that those who are concerned about the rights of women worldwide should be concerned about why they are not being informed of the symptoms of ovulation which are so easily and universally recognizable. Women are fertile no more than 6 to 8 days in the cycle. These easily recognizable signs should empower women to control their fertility. Many females are dissatisfied with artificial contraceptive methods and do not know of the natural family planning alternative. Many subfertile women who desperately want to achieve conception are not being given this basic information that would enhance their chances. The author feels if one looks at this from an ecological feminist, economic family or just plain common sense point of view all women are entitled to this information. 22901 [end, gyn] This study evaluated 481 subjects in 44 geriatric and neurologic units. This was a 150-day trial in 4 different phases. There was a placebo treatment phase for 30 days followed by phase T1 and phase T2 of L-acetylcarnitine (LAC) at 1,500 mg per day for 90 days. Phase T3 included another 30 days of the placebo treatment. There was a significant increase in the total score of the Mini Mental State Examination at the end of the LAC treatment. Memory was also shown to be improved after the LAC treatment. The emotional-affective area showed a significant improvement in total scores as well as the Hamilton Rating Scale. The behavioral- relational aspects evaluated by the Family Stress Scale showed a significant decrease in the total score after treatment. No significant adverse drug reactions were seen during the trial. This study showed a significant improvement in several performance scales in mild mental impairment in the elderly during LAC treatment. 22823 [neu] Sexual functioning after myocardial infarction is rarely discussed by physicians. Even with instructions more than one-fourth of previously sexually active individuals fail to resume intercourse after a coronary event. Those who had a healthy sexual relationship before the heart attack have a much better chance for full recovery of sexual activity. Most of the patients are physically able to resume intercourse after a coronary event, but many have unnecessary fears that interfere with their activity. Some may be reluctant to mention their fears to the physician. As far as medical management, when a patient can walk 5 level blocks comfortably or climb 2 flights of stairs they can safely resume sexual intercourse. Before intercourse, agents such as beta blockers, calcium channel antagonists or nitrates can be taken. In the past, postcoronary patients were told to assume a "passive position and role" during intercourse because this was believed to put less burden on the heart. Extensive research has not confirmed this assumption. In these studies heart rate and blood pressure readings were actually higher when a patient assumed a new position. Thus it is not necessary for couples to change to an unfamiliar position. If the patient complains of chest pain in a certain position he should be instructed to take medication before intercourse or to avoid that position. Masturbation frequently occurs in the hospital the day after a coronary event, many times for psychological reinforcements of the individual's "manhood". It could be potentially dangerous during the first 72 hours after a myocardial infarction. Masturbation should be avoided until one is out of the high risk period for arrhythmias. 21578 [car, gu, gyn] This is a case report of a 65-year-old woman who came to a chiropractor's office for examination and treatment of cervical spine injuries suffered in a deceleration-type automobile accident. She had hit the back of a stopped vehicle at approximately 40 miles per hour. Hospital X-rays were reported to be negative for cervical fracture. Subsequent radiographs of the cervical spine showed the presence of a posterior arch fracture at C2. The patient was referred for further imaging and was treated conservatively with bracing of the cervical spine. After 5 months she had substantial recovery with some residual stiffness and headache. The authors conclude that radiographs taken in emergency care settings are often incomplete for the purposes of screening for contraindications to spinal manipulation. Chiropractors should be extremely cautious in initiating manipulative therapy in those patients having sustained cervical spine trauma and who have had prior X-rays that have been reported to be normal. 21748 [neu, ort] In a rat model alcohol induced liver damage and consumption of high dose vitamin E were evaluated. Chronic ethanol treatment resulted in an increase in thiobarbituric acid reactive substances and conjugated dienes in both normal and alpha-tocopherol supplemented animals. In the animals receiving either dextrose or ethanol and their regular diet there was a significant inverse correlation between liver, vitamin E and thiobarbituric acid reactive substances and conjugated dienes. The vitamin E supplemented rats had significantly positive correlations seen between liver, vitamin E and thiobarbituric acid substances and conjugated dienes. Vitamin E had no effect on ethanol-induced pathologic changes in the liver. These results show that intragastric feeding of vitamin E had no protective effect on ethanol-induced liver damage. 22274 [hep] This study evaluated the correlation between dietary calcium intake and bone mineralization in 55 children and adolescents, 5 to 14 years of age, with a mean age of 9.5 years. Children with only positive RAST testing to cow's milk protein were evaluated. Bone density in the femur and lumbar spine increased proportionately with calcium intake. Calcium intake is important for optimal bone mineralization. Even though calcium intake is not the major determinant of bone loss, it is the simplest and most amenable to safe and effective manipulation. 21595 [all, ort] This is an extensive review article on the role of antioxidants, vitamin C, vitamin E, beta-carotene, and selenium as part of glutathione peroxidase, in the prevention of coronary heart disease. These antioxidants theoretically help prevent LDL oxidation. The authors feel that the antioxidant approach to atherosclerosis is a promising hypothesis but long term intervention studies are needed to determine if this hypothesis is true. The authors don't believe preventive use of antioxidant supplementation is warranted at present. The findings do support the increased consumption of fruits and vegetables. 21562 [car] This is a review article on the role of physical activity and bone loss. A reduction in physical activity may increase the risk to fractures. Exercise training has lead to small changes in bone mineral density. Cross sectional studies of athletes favor strength over endurance type training. Prostaglandin release, piezoelectric and streaming potentials, increased bone blood flow, microdamage and increased hormone release are some of the proposed mechanisms for the induction of signals for new bone formation, following alterations in strain. 21900 [ort] Reversible injection occlusion of vas deferens is a safe, effective and simple method of male fertility control. The incidence of sperm disappearance increased with the duration of reversible injection occlusion of vas deferens and reached 90% at the end of 12 months after operation. Before this procedure the mean value of carnitine in the seminal plasma was 366.9 while after this procedure the mean value of seminal plasma carnitine was 112.7 in the group with sperm disappearance and 172.5 in the group without sperm disappearance. There was a significant difference in carnitine content between preoperation and postoperation. After this procedure the carnitine concentration in the seminal plasma of the group with sperm disappearance was lower than that of the group without the sperm disappearance. These results suggest that carnitine content in the seminal plasma following reversible injection occlusion of the vas deferens may be a way of determining the success or failure of this particular procedure. 22283 [rap, uro] This study evaluated serum levels of manganese and 24-hour manganese excretion by urine in 29 patients with Parkinson's disease and 27 matched controls. There was no difference found between the 2 groups and the authors conclude that serum levels and urinary excretion of manganese are unrelated to the risk of developing Parkinson's disease. 22804 [neu] Twenty subjects who met the criteria for major depression evaluated a 3 day food questionnaire which included the consumption of coffee and refined sucrose in the experimental group or a red meat and artificial sweetener free diet in the control group. Subjects who had depression that was reduced after eliminating refined sucrose and caffeine completed a 3 month follow-up. The experimental group showed a significantly greater reduction in depression on all depression measures and on several measures of general psychopathology on post tests. This reduction in depression was maintained for up to 3 months. 22179 [nut, psy] Sixteen studies were identified and 14 were analyzed for the relationship between estrogen replacement therapy and colon cancer. The overall relative risk of estrogen replacement therapy use in colorectal cancer was 0.92. With the results of all the studies taken into consideration there was no association between estrogen replacement therapy and the incidence of colorectal cancer. 22375 [can] This study evaluated 30 Chileans and El Salvadorians who experienced torture, trauma and non-torture/trauma migraines. The individuals were administered the Post-Traumatic Stress Disorder Scale, SCLR-90-R, and the Impact of Events Scale. The data supports the hypothesis that torture survivors show higher levels of the post traumatic stress disorder, psychosomatic impairment and stress response alterations than the trauma and the non-torture trauma groups. 22696 [tra] Numerous studies have shown that elevated plasma homocysteine concentrations are associated with an increased risk to premature vascular disease. Intracellular homocysteine is metabolized by either the transsulfuration pathway or by remethylation to methionine. The remethylation of homocysteine requires methyltetrahydrofolate and vitamin B12 as a cofactor and as a cosubstrate and coenzyme, respectively. The condensation of serine and homocysteine in the first reaction of the transsulfuration pathway is dependent on pyridoxal 5'-phosphate as a cofactor. It has been well established that vitamin B12 or folic acid deficiencies may result in high hyperhomocysteinemia. Methylmalonic acid concentrations in the serum can be used to differentiate between B12 and folic acid deficiencies. Evidence is reviewed regarding these homocysteine lowering nutrients and supports their involvement in atherosclerosis. It is noted, though, that even with all the evidence associating homocysteine with the pathogenesis of coronary heart disease, the effects of homocysteine lowering therapy on coronary heart disease incidence needs to be investigated further in randomized, double-blind, controlled trials which are currently being planned. It obviously will take several years for the results of these trials to be known. In the meantime the authors of this article believe that physicians and nutritionists should concern themselves with homocysteine. Health professionals must outweigh the risk and benefits in the absence of complete information. The correct treatment of elevated plasma homocysteine concentrations with innocuous vitamin supplements does not pose any health risk but may have significant benefits in slowing coronary heart disease progression. It may therefore be prudent to screen for and treat hyperhomocysteinemic patients with a family history of high coronary heart disease incidence. 22498 [cad] In rats exposed to subtoxic levels of selenite, vitamin B12 status was evaluated by urinary methylmalonic acid excretion and by liver and plasma vitamin B12 levels. Selenium absorption was not effected by vitamin B12 dietary intake. A significant interaction of vitamin B12 and selenium was found on the growth of rats fed vitamin B12 deficient or controlled diets. In the vitamin B12 depleted rats there were signs of changes in the liver. In those who were supplemented with B12 there was no gross or histologic evidence of liver toxicity. Rats fed 9 mg/kg of selenium with B12 had significantly lower liver and kidney selenium levels and a significantly higher blood selenium than those fed the diet without vitamin B12. These results support the hypothesis that vitamin B12 deficiency limits selenium methylation and excretion, resulting in higher tissue selenium levels and subsequent toxicity. Selenium methylation is dependent upon vitamin B12 acquired pathways. 21586 [nut] This is a review article on the role of behavior monitoring and intervention and the secondary prevention of ischemic heart disease. Studies show that anger, depression and anxiety are major factors in the development of ischemic heart disease. Anger is a strong predictor in the development of ischemic heart disease. The resistance to utilizing behavioral modification is not necessarily based on science as much as the resistance is largely due to paradigmatic scotomata, which is conceptual difficulties for those individuals who are not familiar with biopsychosocial research. Routine evaluation of ischemic heart disease patients with psychometric assessment may provide a cost effective way of getting cardiologists and internists to recognize the elevated levels of emotional stress in their patients. It is rare that cardiologists read psychosomatic journals. An alternative is publishing articles relating to behavior and cardiovascular disease in peer review cardiology-type journals. 21539 [car] This is a case report of a 43-year-old male, with habitual alcohol intake of 150 mg per day until 1 year before admission. It was noted, upon admission, that he had progressive weakness and paresthesias in his legs and hands. He had had a vagotomy and pyloroplasty because of peptic ulcer 4 years before admission and had been on omeprazole for 3 years. Neurophysiological study revealed axonal polyneuropathy. The polyneuropathy had been getting worse since admission and empirical treatment with intravenous methylprednisolone at 1 gm daily was started on the 1st day of fibreoptic gastroscopy. Two days after the 2nd fibreoptic gastroscopy, the patient experienced sudden chest pain and a chest film showed a dilated heart. Within 4 days he developed acute pulmonary edema. He was suspected of having fulminant beriberi and treated with 200 mg of thiamine given intravenously daily. After a few hours there was progressive clinical improvement. The cardiac silhouette returned to normal on the 4th day. Factors that were involved in the development of the beriberi included empirical treatment with high doses of corticosteroids and the second was large amounts of glucose administered intravenously during the 36 hour fast before the 2nd fibreoptic gastroscopy. The need for vitamin B1 is highest when carbohydrates is the main source of energy. The authors recommend a multi-vitamin treatment for all patients with a history of alcoholism in order to rule out polyneuropathy caused by vitamin deficiency. Also to avoid hyperglycemia and polyneuropathies of unknown etiology when corticosteroid treatment is planned, thiamine should be given. 22850 [car, neu, nut] Ten cirrhotic patients, between 48 and 65 years of age, were evaluated over a 2 month period while taking S-adenosylmethionine (SAMe) at 800 mg per day. There was no significant change found in the percent composition of biliary amino acids except for an increase in glutamic acid and taurine. There was a trend towards increased percent tauroconjugation of all individual bile acids. There was a significant increase in taurochenodeoxycholic acid and a drop in glycocholic acid. In the cirrhotic liver exogenous S-adenosylmethionine is partially metabolized to taurine which is used for a bile salt. The authors conclude that giving S- adenosylmethionine to cirrhotic patients enhances bile salt tauroconjugation. 21524 [gas] This 10-month study evaluated 28 college females between 18 and 25 years, of which 26 were white, 1 black, and 1 Indian. Seventeen of the subjects were athletic and were recruited from university sports programs, 11 were selected from among their peers and identified through questionnaires as individuals who did not get regular exercise. Three mg of boron were given daily. The individuals continued to consume their normal, self- selected, typical Western diet. Serum phosphorous concentrations were lower in the boron- supplemented subjects than the placebo- supplemented subjects. Compared with all other subjects, serum magnesium concentrations were greatest in the sedentary control subjects supplemented with boron and increased with time in all subjects. Exercise training reduced changes in serum phosphorous concentrations caused by boron supplementation. Calcium excretion increased over time in all the groups combined, and boron excretion increased over time in all boron-supplemented subjects. These results suggest that boron supplementation modestly affected mineral status, and that exercise modified the effects of boron supplementation on serum minerals. These findings do not support the work of Nielsen, who found that in postmenopausal women fed low amounts of boron at 0.23 mg per day, boron supplementation elevated plasma normalized calcium and had no effect on plasma total calcium. Magnesium levels, in general, tended to be on the low end of normal. The young female athletes in the study who showed low serum magnesium concentrations and who were voluntarily consuming a low-magnesium diet may be at risk for development of bone metabolism disorders. Blood magnesium values were influenced by activity, being higher in sedentary than in athletic individuals. Boron supplementation was associated with lower serum phosphorous concentrations. Increasing both dietary calcium and boron may be beneficial in balancing blood minerals to optimize bone mineralization during the final developmental period. The author notes there has been widespread interest over the years in assuring adequate calcium intake at critical stages of the female life cycle. This interest should be extended to optimal intakes of all minerals known or suspected to affect bone density, such as calcium, phosphorous, magnesium, and boron. 21766 [ost, end] There are 3 authorized claims with respect to heart disease accepted by the food and drug administration. These include dietary saturated fat and cholesterol, coronary heart disease; fruits, vegetables and grain products that contain fiber, particularly soluble fiber and the risk of heart disease and sodium and hypertension. Approval of a health claim is based on the totality of the publicly available scientific evidence and significant agreement among experts qualified by scientific training and experience to evaluate the particular relationship. On January 4, 1994 the FDA finalized requirements for health claims on dietary supplements. It is noted that the role of omega-3 fatty acids in heart disease is not authorized as well as dietary fiber by itself in heart disease is not authorized. 22347 [car] This study evaluated 17 male healthy subjects between 20 and 40 years of age who consumed fermented soy products of 112 gm of tempeh or unfermented soy at 125 gm soybean pieces. Urinary excretion of isoflavonoids was higher and the excretion of lignans was lower when the subjects consumed soy supplemented diets than when they consumed their regular diet. Urinary isoflavonoid excretion and lignan excretion were similar when subjects consumed tempeh and soybean pieces diets. The recovery of daidzein and genistein was significantly higher when these subjects consumed the tempeh diet than when they consumed the soybean pieces diet. When fed soy 5 of 17 subjects secreted high amounts of equol. Fermentation of soy decreased the isoflavone content of the product fed but increased the urinary isoflavonoid recovery. This suggests that fermentation increases availability of isoflavones in soy. The level of soy believed to be necessary for the reduction of cancer risk is currently above the average of soy intake of 3 gm per day in the United States. The intake of soy products by Americans increased approximately 40% from 1980 to 1990. With this continuation of trend and the addition of new soy products on the market many Americans could reach the proposed levels of soy consumption in the near future. 22382 [can, nut] This study evaluated 41 nonpregnant females who gave birth to neural tube defect children and 50 control women who previously had normal offspring for homocysteine levels and for fasting blood levels of folate, B12 and B6. The mean values for basal homocysteine and homocysteine following a methionine load of 0.1 gm of L-methionine per kg body weight were significantly increased in the group of women who previously had had neural tube defect infants. In 9 of these subjects and 2 of the controls, the values after methionine ingestion exceeded the mean control by more than 2 standard deviations. These findings suggest a disorder in the remethylation of homocysteine to methionine due to an acquired nutritional or inherited abnormality in folate or vitamin B12 metabolism. Increased homocysteine levels can be normalized by the administration of vitamin B6 or folic acid. The authors recommend the prevention of neural tube defects by periconceptional folate administration which could effectively correct a mild to moderate hyperhomocysteinemia. The doses utilized of folic acid were between 4 mg and 5 mg. 21813 [neu, obs] This study evaluated 8,981 patients with multivessel coronary artery disease who were screened at 8 clinical sites. Three hundred and fifty-nine were randomized to either undergo coronary artery bypass surgery (177 patients) or percutaneous transluminal coronary angioplasty (182 patients). After coronary artery bypass grafting hospitalization was longer and Q wave myocardial infarction in relation to the procedure was more frequent whereas in hospital mortality did not differ significantly between the 2 groups. At discharge 93% of the patients in the coronary artery bypass grafting group were free of angina compared to 82% of those in the percutaneous transluminal coronary angioplasty group. During the first year of follow-up 44% needed further intervention in the angioplasty group but only 6% in the coronary artery bypass group. Seventy-four percent of the patients in the coronary artery bypass group and 71% in the angioplasty group were free of angina after 1 year of treatment. Exercise capacity improved similarly in both groups. Twenty-two percent of the coronary artery bypass group as compared to 12% of the angioplasty group did not require antianginal medication. In selected patients with multivessel coronary artery disease percutaneous transluminal coronary angioplasty and coronary artery bypass grafting as initial treatments resulted in equivalent improvements in angina over 1 year. In order to achieve similar clinical outcomes the patients treated with angioplasty were more likely to acquire further interventions than antianginal drugs whereas the patients treated with bypass grafting were more likely to sustain an acute myocardial infarction at the time of the procedure. 22123 [car] Dietary nucleotides can be synthesized endogenously and are thus not essential nutrients. Dietary nucleotides have beneficial effects upon immune function, small intestinal growth and development, lipid metabolism and hepatic function. Natural sources of nucleotides include human milk, organ meats, seafood and legumes. Nucleotides are reported to have significant effects on lymphoid, intestinal and hepatic tissues and lipid metabolism. The mechanism remains unknown. The nutritional role of nucleotides is controversial. Preformed nucleotides supplied by the diet may contribute to tissue nucleotide pools and optimize the metabolic functioning of rapidly dividing tissue as those of the gastrointestinal and immune system. Exogenous sources of nucleotides may be important in individuals with marginal dietary intakes of nucleotides and/or tissues which have an increased need such as rapidly growing infants fed mostly cow's milk based formulas and individuals with disease related immunosuppression, intestinal or liver injury. Nucleotides are nucleic acid precursors, and they are potent inter and intracellular biological mediators. The reported effects of dietary nucleotides in human and animals include promotion of small intestinal growth, increased small intestinal dissacharidase activity, intestinal hyperemia, protection against diarrheal disease, effects upon stool flora, enhanced cellular and humoral immunity, enhanced effect upon hepatic composition, increased blood levels of long chain polyunsaturated fatty acids and effects upon serum lipoproteins. 22448 [nut] The cholesterol lowering effect of soy protein has been documented in many species even though it is not understood. This study evaluates the relationship between dietary protein sources and plasma thyroxine concentrations. The theory is that soy protein lowers plasma cholesterol by increasing plasma thyroxine concentrations. Animal studies show that feeding soy protein to laboratory animals consistently elevates plasma thyroxine concentrations. Elevation in plasma thyroxine concentrations comes before changes in plasma cholesterol concentrations which is important to produce a causative effect. It is concluded that there is consistent evidence that dietary protein can increase T4 levels. 22634 [car, end] Epidemiologic studies in various countries and in the United States in the last century suggest decreased omega-3 fatty acid consumption correlates with increasing rates of depression. This is consistent with a well established positive correlation between depression and coronary artery disease. Long chain polyunsaturated fatty acid deficiency may contribute to depressive symptoms in alcoholism, multiple sclerosis and postpartum depression. Adequate long chain polyunsaturated fatty acids, particularly docosahexaenoic acid (DHA), may reduce the incidence of depression just as omega-3 fatty acids may reduce the incidence of coronary heart disease. 22756 [car, psy] This study evaluated 548 males 40 years after their birth of which 253 had been exposed to diethylstilbestrol in utero compared to 241 who had not been exposed. Congenital malformations of the genitalia were reported 3 times as often by diethylstilbestrol exposed men as by sons of women in the placebo group. In the exposed group malformations were twice as often reported among those exposed to diethylstilbestrol before the 11th week of gestation as among those exposed later. Men with genital malformation were as fertile as other men. Diethylstilbestrol- exposed men had no impairment of fertility in any measure. Diethylstilbestrol-exposed men had no impairment of sexual function. The authors concluded that high levels of diethylstilbestrol did not lead to impairment of fertility or sexual function in adult men who had been exposed to the drug in utero. 22474 [rep] A study evaluated 226 pregnant females who smoked and had lower concentrations of vitamin C in their blood compared to 174 nonsmoking pregnant females. Their fetuses got comparatively less vitamin C even when both women had the same vitamin C concentrations. This suggests that smokers may need more vitamin C and maybe more of other nutrients that have not been identified to receive the appropriate amount of nutrients across the placenta to the fetus. The New York team followed the 400 women through their pregnancies and have found a striking difference in the amount of vitamin C in their blood streams. On the average the smokers had 15% less vitamin C than nonsmokers. It appears that smoking mothers develop a biological craving to contain vitamin C containing foods and juices. It is typical that newborns have twice the vitamin C concentration as their mothers. In smokers the expelling of the placenta takes nearly twice as long. Another study is to be done on whether low vitamin C, which plays a role on connective tissue development, prolongs the final stages of labor. 22573 [nut, rep] This study evaluated serum ionized magnesium levels during intravenous magnesium sulfate therapy of preeclampsia in a female cohort who received a bolus of 4 gm of magnesium sulfate mixed with a 50 ml solution of 5% dextrose-Ringer's Lactate given over 30 minutes followed immediately by a continuous infusion of 2 gm of magnesium sulfate in 50 ml of 5% Ringer's Lactate per hour. There was a strong correlation between ionized and total magnesium throughout the therapy. 22921 [gyn, obs] Vitamin E succinate which is a derivative of natural vitamin E can inhibit the proliferation of several types of cells in culture. The antiproliferative properties of vitamin E succinate appear to be unique to this particular tocopherol compound since RRR-alpha-tocopherol, RRR-alpha-tocopherol acetate, and all-race- à-tocopherol do not inhibit antiproliferative properties in most cell culture systems. Studies suggest that vitamin E succinate's antiproliferative effects are unique to this form of vitamin E and appear to not involve antioxidant effects. There is evidence that vitamin E succinate may activate transforming growth factor TGF-beta growth-inhibitory signaling system. 22990 [nut] A discriminate analysis involving data from the Scottish Heart Health Study regarding antioxidants in coronary heart disease showed that the combined dietary intakes of the antioxidants C, E and carotene differentiate coronary heart disease prevalence as well as the classical risk factors. In women, step wise discriminate analysis showed that the effect of antioxidant vitamins on coronary heart disease is removed by adjustment for the classical risk factors and aging. The authors concluded that dietary antioxidants appear to have a significant effect on the prevalence of coronary heart disease, especially among men. 22514 [car] Hand gun violence is generally a preventable disease that kills 40,000 individuals annually and harms another 240,000 in the United States. Its direct and indirect costs annually are greater than 14 billion dollars, 80% of which is picked up by the tax payer. About 1/4th of those who are involved in the hand gun violence are between 15 to 24 years of age. In this interview with senior staff physician, Dr. John May from the Cermak Health Services of Cook County, who is an advocate of balance, intervention and prevention, an acronym for guns is outlined. The acronym is "G-Is a gun in your home?", "U-Are you around users of alcohol or drugs?", "N-Do you feel a need to protect yourself?", "S-Do any of these situations apply: Seen or being involved in acts of violence? Sadness? School-aged children at home?" Patients in high resident areas are receptive to this idea. When physicians recognize violence as a public health issue they create the framework of preventive strategies. Physicians should be advocates for healthier and safer communities. Speaking at school and to community groups provides physicians with an opportunity to educate the public about the health risks of firearms. Dr. May notes that medical practice evolves as health challenges evolve. There is an epidemic of firearm injuries and deaths at present. The author encourages physicians to counsel his or her patients about the risk of firearms. 22608 [tra] Seven hundred and thirty men and women were evaluated by a 7 day dietary record who had no history of cardiovascular disease. In these elderly subjects the mortality from stroke was highest among those with the lowest vitamin C. Those in the highest 3rd of distribution of vitamin C had a relative risk of .5 compared with those with the lowest third after adjustment for age, sex and cardiovascular risk factors. The relationship between vitamin C and stroke was independent of social class and other dietary variables. There was a similar associated risk with plasma vitamin C concentrations. There was no association between vitamin C status and the risk of coronary heart disease. The authors conclude that in elderly subjects vitamin C concentration whether measured by the diet or plasma is strongly related to the subsequent risk of stroke but not to coronary heart disease. This study followed-up elderly subjects over a 20-year period. In this study vitamin C was as strong a predictor of death from stroke as diastolic blood pressure. Oxidation of LDL cholesterol may enhance the likelihood of an atheroma which vitamin C may have an effect on. Antioxidants may be important in the prevention of cerebrovascular disease. In this study vitamin C status predicted death from stroke. Part of the decline that has occurred from cardiovascular disease may be due to increased consumption of fruits and vegetables. A high intake of vitamin C should be encouraged in the elderly. 22724 [car] The Gottingen Risk Incidence and Prevalence Study (GRIPS) included 6,002 men, aged 40-59.9 years at baseline. Data from a 5-year follow-up is now available from 95% of the participants. This study provides the opportunity to evaluate the impact of Lp(a) as a cardiovascular risk factor on the basis of a large-scale study. Multivariate logistic regression models for the estimation of MI risk confirmed Lp(a) as a significant risk factor, ranking fifth behind LDL cholesterol, family history of MI, plasma fibrinogen, and HDL cholesterol. The data strongly supports strategies for the identification and treatment of persons at increased MI risk which focus on LDL cholesterol. Lipoprotein(a) and fibrinogen need to be considered as additional risk factors. 21789 [car] This article reviews the role of prevention in health care reform. Since 1960 prevention of heart disease through lifestyle changes has had a significant impact. Congress has been slow to act on incorporation of preventive treatments in health care reform. President Clinton's package included cholesterol screening, immunizations and regular clinician visits as a means of prevention. A volunteer, Dr. Charles Francis, testified for the need for preventive benefits such as hypertensive screening, exercise and nutritional counseling and smoking cessation to reduce death and disability from cardiovascular disease, which is the nation's #1 killer. Cardiovascular disease is the leading cause of death in women; the American Heart Association highlighted a need for continued research in the area of cardiovascular risk factors for women and the rise in smoking in teenage females. Prenatal care was to be considered a covered benefit with no copayments employed; obstetricians and gynecologists would be considered a woman's primary care physician. Child care and lead screening would also be included in the preventive benefit package. The estimated cost for cardiovascular disease in 1994 by the American Heart Association is 128 billion dollars. This includes the cost of physicians and nursing services, hospital and nursing home services, the cost of medications and loss of productivity. Cigarette smoking is the major preventable risk factor for cardiovascular disease. Nutritional counseling has been recommended as essential to primary and secondary prevention of myocardial infarction as well as cardiovascular disease. Health care reform needs to include: nutrition/weight control counseling, high blood pressure, smoking cessation, physical activity and health risk assessment and educational activity. In addition, it should include signs and signals for survival during cardiovascular emergencies such as heart attack and stroke. Prevention and preventive health programs should not stop with health care reform but must be integrated into all government programs involving wellness. Schools are an ideal place for children to start to learn good lifestyle behaviors. The American Heart Association has distributed its recommended basic preventive cardiovascular services to every member of congress . . . but citizen input is needed so that the message of true health care reform through prevention is delivered to congress. 21352 [car, pre] This study evaluated healthy, postmenopausal women who were at least 2 years from the last menstrual cycle. Twenty-eight women were using estrogens and 43 were nonusers. In the estrogen users most were taking conjugated estrogen and approximately 1/2 were receiving a progestin. The estrogen users had better immediate and delayed verbal memory scores than the nonusers. The improvement in verbal memory in the estrogen users was not affected by progestin use. Estrogen use in healthy postmenopausal women is associated with better performance on specific memory tests. Other cognitive function was not affected by the estrogen. 21548 [end, gyn, neu] Smoking and diet contribute to 2 of every 3 cases of cancer. Preventive measures can reduce the risk of cancer of the lung, head, neck, skin and possibly breast, colon and uterine cervix. The National Cancer Institute estimates that early detection practices may reduce U.S. cancer mortality rates by 25%. Early detection is an accepted approach for cancer of the breast, uterine cervix, skin, mouth and thyroid gland. The early signs of cancer should be taught by the primary care physicians and patients need to act at the first sign. The American Society Cancer Prevention Guidelines include cessation of smoking and smokeless tobacco; maintaining desirable body weight; eating a varied diet; eating at least 5 servings of fruits and vegetables daily; eating more high fiber foods and whole grain cereals, breads and pastas and vegetable and fruit; cutting down on total fat intake less than 30% of the total caloric intake; limiting consumption of alcohol to more than 2 drinks per day; limited salt-cured, smoked and nitrate-cured foods; and keeping sun exposure to a minimum. Monthly self-examination for the breast, oral cavity, skin and testicles should be done. Annual exams for the breasts should be done over the age of 40, pelvic exams over the age of 18, colon and rectal exams over the age of 40, oral exams at any age, prostate over the age of 50, skin over the age of 40, testicular at any age and thyroid over the age of 40. Cancer detection guidelines from the American Cancer Society include a change in bladder or bowel habits, sores that do not heal, unusual bleeding or discharge, a thickening or lump, indigestion or difficulty in swallowing, obvious change in a mole or wart and a nagging cough or hoarseness. Cancer Prevention and Detection Services Resources can be obtained at the American Cancer Society at 1 (800) ACS-2345, the National Cancer Institute at 1 (800)-4-Cancer and the Cleveland Clinic Cancer Awareness Line at 1 (800) 862-7798. 22743 [can] This is a case report of an 83-year-old female who was admitted for increasing congestive heart failure and worsening renal function. She denied a history of digoxin use and was given a loading dose of 1 mg of digoxin over 14 hours on the day after admission and an additional 125 mcg on day two. Six hours later she developed multiple ventricular arrhythmias including ventricular tachycardia. She then divulged a prior history of digoxin treatment. Her serum digoxin level was greater than 6.2 nmol/L 8 hours after her last dose. Her admission digoxin level was found to be at the very upper border of normal. She was admitted to the coronary care unit and given an IV bolus of 2.47 gm (10 mmol) of magnesium sulfate, injected over 5 minutes. Five minutes later her ventricular tachycardia stopped and she developed a junctional rhythm with a ventricular rate of approximately 90 bpm. Within a few minutes a stable rhythm emerged. After approximately 15 minutes she developed intermittent bursts of non-sustained monomorphic ventricular tachycardia lasting up to 30 seconds without any clinical deterioration. Another 2.47 gm of magnesium sulfate was given over 5 minutes followed by a return of the junctional bigeminy. She developed, over the next several days, episodes of nonsustained ventricular tachycardia. On day 9 her serum digoxin level was at 3.0 nmol/L and she was discharged on day 10. Sixteen days after her admission her digoxin was 1.8 nmol/L. Digoxin binds to and inhibits the sarcolemma sodium/potassium ATPase pump leading to increased intracellular calcium concentrations, which enhances myocardial contractility. Magnesium enhances the action of the sodium/potassium ATPase pump without affecting the binding of digoxin. Intravenous magnesium has been shown to stop the digoxin-toxic cardiac arrhythmias in patients without overt heart disease. Hypermagnesemia is unlikely to occur with an initial bolus of 10 to 20 mmol of magnesium, but possibly could occur with continuous infusions or with repeat doses in patients with digitalis toxicity. Intravenous calcium is the antidote and should be kept available. 21745 [car] Seven patients with bullous pemphigoid were given a regimen of 2 gm of Tetracycline combined with 2 gm of nicotinamide daily. There was total remission achieved within 6 to 8 weeks after which the dose was gradually tapered. The duration of therapy was approximately 7 months. The mode of action is unknown. Suppression of chemotaxis of neutrophils and eosinophils is thought to be important. Systemic steroids do not appear to clear the bullous eruptions more rapidly than this combination therapy or prevent relapses. This therapy should be considered as the treatment of choice for bullous pemphigus. 22867 [der] This study evaluated 2,906 healthy, nonsmoking males on health habits and physical activities and a symptom-limited exercise test. There was a gradual increase in high density lipoprotein cholesterol observed with increased miles run. Most of the changes were associated with distances of 7 to 14 miles per week. Levels of low density lipoprotein cholesterol, triglycerides and the ratio of total cholesterol to HDL lipoprotein cholesterol also improved with weekly mileage. The HDL lipoprotein cholesterol levels correlated significantly with all exercise components, anthropometric measurements and alcohol consumption. These results suggest a dose-response relationship between miles run per week, high density lipoprotein cholesterol and other lipoprotein-lipid levels. Most of the changes occurred in those who ran between 7 and 14 miles a week at a mild to moderate intensity. It is also noted there is a higher risk of injury (foot, ankle, knee, hip) with higher mileage. It appears unnecessary and perhaps counterproductive for most people to jog beyond 14 miles per week to increase HDL-C levels. 21885 [car, exe] Humans and animals cannot synthesize omega-6 and omega-3 fatty acids. The fatty acids present in tissue, including cancer cells, are ultimately derived from the diet. The fatty acid content and composition of the tumor is subject to modification, depending on the type and the amount of fat available in the cells. Polyunsaturated fatty acids are very important to the cell membrane and are precursors or components of bioactive lipids that have regulatory functions. Any property or function of the tumor that is related to polyunsaturated fatty acids should therefore be able to be manipulated by diet or supplementation. Docosahexaenoic acid (DHA) supplements may augment the cytotoxicity of existing modalities. The DHA alone will probably not produce enough growth inhibition to be therapeutically effective. Loading the tumor with DHA which could enhance the free radical response produced by cytotoxic agents like Doxorubicin or ionizing radiation may be more effective. A second approach in the utilization of fatty acids is to develop conjugated fatty acids, a new class of chemotherapeutic agents, using parinaric acid as a prototype. It has been shown that cis-parinaric acid, a polyunsaturated fatty acid containing 4 conjugated double bonds, can sensitize the U937 cells to environmental stress. Parinaric acid may sensitize the tumor cell to ordinary levels of oxidant stress. It is not known whether these fatty acid approaches will sensitize normal tissue causing an increase that is unacceptable in generalized toxicity. It is also not known whether either of these approaches is effective in animal or human models. 22649 [can] The author notes that the data suggests that the therapeutic benefits of ursodeoxycholic acid are superior to colchicine for the treatment of primary biliary cirrhosis. The main concern with ursodeoxycholic acid is the relatively high cost. Other than that it seems to be as safe and as well tolerated as colchicine. Present ursodeoxycholic acid is the favored treatment among hepatologists for primary biliary cirrhosis. 22647 [gas, hep] This study evaluated 96 children of which 58 were boys and 38 were girls. A total of 713 days of food diaries were collected with a mean of 7.4 days per child. A total of 1,057 foods containing caffeine were identified on food diaries and were classified into 6 categories which included soft drinks, tea, baked goods, dairy beverages, candy, and desserts. In the last 4 categories caffeine came from chocolate contained in the foods. None of the children consumed coffee. The mean ages of the boys were 8.4 years and the girls were 8.1 years. The boys consumed more caffeine than girls (17 mg/d vs 14.4 mg/d). Even when adjusting for increases in body weight caffeine consumption tended to increase with age averaging .44, .46, .53 and .68 mg/kg per day for the 4 age groups respectively. Caffeinated soft drinks and chocolate contained almost all the caffeine. Approximately 55% from soft drinks and 38% from chocolate. Baked goods contained 17%, dairy beverages 11%, candy 5% and dairy desserts 5%. Only 7.6% of the caffeine was obtained from tea and then from coffee. The major source of caffeine in our study was caffeinated soft drinks. Soft drinks provide about 26% of the caffeine, but tea was the larger source. This data suggests that the levels of caffeine intake in young children may be less than previously thought. The intake of caffeine from soft drinks and chocolate-containing foods by children in this study was similar to that of previous reports. Consumption of tea and coffee by these children was minimal. Regional patterns of caffeine- containing foods, especially tea and coffee, should be taken into consideration when evaluating caffeine intake. 22794 [nut] This study evaluated the fatty acid status of 102 pregnant women in their third trimester. The women were from low subeconomic communities with an average household income of less than $175.00 per month. They were between 17 and 37 years of age, with gestational periods between 25 and 36 weeks. Dietary information was only available from 72 out of the 102 pregnant women. Fourteen percent delivered preterm infants, defined as those infants delivered less than 37 weeks of gestation. Half of those were low birth weight infants. The main finding in this study was that there was an imbalance of omega-6 to omega-3 fatty acids in all the pregnant women. Women who delivered low birth weight infants had reduced levels of alpha-linolenic acid and increased levels of stearic acid. Daily intake of omega-3 fatty acids appeared to be adequate based on the 1.36 g/d for pregnant women in the third trimester. Most of the dietary omega-3 fatty acids were in the form of alpha-linolenic acid which is poorly converted to long chain polyunsaturated fatty acids, resulting in a reduced availability of fatty acids. The reduced levels of alpha-linolenic acid reflect an inadequate intake of dietary alpha-linolenic acid, despite contrary information provided by a questionnaire that the women had filled out. This study also suggests that the intake of omega-3 fatty acids could be inadequate. The daily intake of omega-6 fatty acids exceeded the recommended 7.9 gm. High levels of linoleic acid reduce the conversion of linoleic acid and alpha- linolenic acid to their respective, long chain C20 and C22 metabolites. The reduced levels of alpha-linolenic acid suggests that even less of the alpha-linolenic acid metabolites will be formed in the presence of high linoleic acid levels, since both fatty acids compete for the same enzyme system. This has serious consequences for the developing fetus since a reduced level of omega-3 fatty acids can affect learning, behavioral, visual, and retinal functions in low birth weight infants. Pregnancy may result in essential fatty acid deficiency as a result of physiological stress. Pregnant women's diets should be modified to contain less linoleic acid and more alpha-linolenic acid so the manufacturing of long chain polyunsaturated fatty acids is optimized. Pregnant women should consume fatty fish regularly so that they may get adequate amounts of docosahexaenoic acid. Fish consumption can increase birth weight by prolonging the gestation period. Smoking abolishes the positive effects of fish omega-3 fatty acids on birth weight. Pregnant women should eat more fish containing long chain omega-3 fatty acids. They should also consume less omega-6 fatty acids by avoiding the frying of food in sunflower oil, which is high in linoleic acid. Boiling, baking or roasting fish without any added fats should be recommended. 21673 [nut, obs, ped] Epidemiologic data states that a high intake of nitrates and nitrosyl compounds, early introduction of cow's milk into the diet, and a short duration or an absence of breast feeding increases the risk of insulin dependent diabetes mellitus. Studies in experimental animals show that cow's milk and soy protein may be diabetogenic. There is interest in the effects of free radical scavengers, such as niacin (vitamin B3) and natural and synthetic antioxidants, on insulin dependent diabetes mellitus. Abdominal obesity is a high risk factor for noninsulin dependent diabetes. Weight management is very important in this group of subjects. 21565 [end] This study included 16 patients with generalized peroxisomal disorders with a diagnosis of either Zellweger's Syndrome or neonatal adrenoleukodystrophy plus 1 patient with isolated bifunctional enzyme deficiency. These patients were between 3 months and 3 years of age. Total fatty acid methyl esters were evaluated. DHA deficiency is a constant finding only in generalized peroxisomal disorders. Under good nutritional conditions X-linked adrenoleukodystrophy and adrenomyeloneuropathy patients have normal levels of DHA as well as other polyunsaturated fatty acids at least in the red blood cells. The data shows that nutrition plays an important role in altering DHEA levels. It is difficult to explain the extreme DHA deficiency in the peroxisomal brain. DHA should be provided to all peroxisomal patients with a clear DHA deficiency. The low values of plasma arachidonic acid in patients with generalized peroxisomal disorders was surprising considering the high levels of polyunsaturated fatty acids in the brains of Zellweger's Syndrome. The low concentration of arachidonic acid in the plasma could be of nutritional origin or possibly of a deficiency of delta 5 or a delta 6 desaturation. It is possible that the low plasma arachidonic acid level could be related to the poor growth in these patients. Normalization of plasma arachidonic acid in conjunction with DHA therapy is recommended since omega-3 fatty acid supplementation alone may cause a further reduction in omega-6 polyunsaturated fatty acids.22353 [neu, nut] In many parts of the world diarrhea that goes on for more than 2 weeks and is associated with malabsorption or altered growth is a major health problem in infants and children. Diarrhea lasting more than 2 weeks is defined as persistent diarrhea. Many times the cause of persistent diarrhea is unknown. Children under 2 years of age are at greatest risk for chronic diarrhea. Breast feeding appears to be protective. Infants who receive mainly animal milk products appear to have a greater stool output and a longer duration of illness than breast fed infants. Other factors in persistent diarrhea include dietary lactose, protein sensitization and osmolality. Evaluation of persistent diarrhea includes a history, physical examination, urinalysis, CBC, sedimentation rate, electrolytes, protein, albumin, liver function, immunoglobulins, the trace minerals (iron, calcium, magnesium, phosphorous, zinc, copper, selenium), vitamins (A, D, E & B complex), stool pH, guaiac, reducing substances, ova & parasite testing, 72-hour fecal fat collection and electrolytes. Special tests include D-xylose, lactose hydrogen breath test, small bowel biopsy, sigmoidoscopy and x-rays. Treatment involves aggressive nutritional repletion. The osmolality of the oral solution should be less than 350 mOsm/L. Important micronutrients includes vitamins A, K, B complex, thiamine, folic acid, iron, zinc, copper, calcium, phosphorous, magnesium and selenium. Of these, vitamin A and zinc have the most important roles in diet therapy of persistent diarrhea. An initial caloric intake of 50 to 100 kcal per kg per day of a nutritionally sufficient diet can be well tolerated. An increase of 25 kcal per kg per day every 1 to 2 days can be instituted if the child tolerates the diet. Maximum weight gain appears to occur at a caloric intake of approximately 140 to 200 kcal/kg/day. 21501 [gas, nut] This is a case report of a 28-year-old female who had a severe headache after ingesting a large quantity of ethanol-extracted ginseng. Cerebral angiograms were consistent with cerebral arteritis. There was a close time association between ginseng intake and the cerebral arteritis which suggests a causal relationship. The recommended daily dose for dry ginseng root is generally between .5 and 2 gm. 22626 [neu] In a recent study in Arteriosclerosis and Thrombosis and Vascular Biology, 1995;15:169-178 it was shown that eggs eaten every day may increase blood cholesterol levels only moderately. This study was funded by the American Egg Board and the National Heart, Lung and Blood Institute. Thirteen women ages 21 through 25 ate either 3 eggs a day, 1 egg a day or a powdered egg substitute in addition to the diet recommended by The American Heart Association. Women followed each of the egg diets for 8 weeks, followed by a washout period between each diet. For every 100 mg of dietary cholesterol added to the diet per day, the total fasting cholesterol concentration increased by 0.073 mmol/L, LDL cholesterol increased by 0.054 mmol/L and the HDL cholesterol increased by 0.015 mmol/L. There were a wide range of responses among the women. Last year, New York researchers found that 20 young men who ate up to 4 eggs per day for 8 weeks had no significant rise in their cholesterol levels. The American Heart Association and the National Cholesterol Education Program recommended a diet that contains no more than 3 or 4 eggs per week. This study seems to indicate that some healthy individuals can pay less attention to their egg consumption if they maintain a low cholesterol level and low heart disease risk profile. However, for most Americans even small adverse effects of dietary cholesterol can increase the overall risk to coronary heart disease. 21927 [car] Four hundred and fifty females, between 35 and 79 years of age, with ovarian cancer were interviewed regarding reproduction and diet. They were compared to 564 randomly selected controls. Saturated fat consumption was associated with an increased risk of ovarian cancer, with an odds ratio of 1.2 for each 10 gm per day of intake. No relationship was seen with the intake of unsaturated fats. Egg consumption resulted in an increased risk of 1.42 for each 100 mg of egg cholesterol per day. Consumption of vegetable fiber, but not fruit or cereal fiber, was associated with a decreased risk, with an odds ratio of .63 for each 10 gm of fiber per day. Reducing the intake of saturated fat and consuming more vegetables appears to lower the risk of ovarian cancer. 21521 [can, gyn] This study evaluated the effects of 1 gm of oral calcium, given as calcium carbonate, on 13 normal men between 51 and 70 years of age. Calcium supplementation was associated with an increase in plasma ionized calcium and a decrease in plasma parathyroid hormone. After the calcium load there was a decrease in urinary hydroxyproline-creatinine ratio from 11 to 7.9. The urinary deoxypyridinoline-creatinine ratio was reduced from 14 to 10 and the urinary pyridinoline-creatinine ratio from 52 to 40 between baseline and 6 hours later. No changes in osteocalcin were noted. This study shows that a 1 gm load of elemental calcium from calcium carbonate suppressed certain biochemical markers of bone resorption for more than 6 hours in normal men. This supports the concept that calcium supplementation may be used in the prevention of bone loss in males. 21457 [end, nut, ort] An oral load of 200 mg of caffeine was given to 13 patients with chronic liver disease and 11 healthy controls. Plasma and urinary excretion of caffeine and its metabolites were evaluated. The caffeine was given orally to 6 patients to confirm the excretion through different pathways. The median half lives of caffeine were 19 hours in the patients and 3.8 hours in the controls. This wide range suggests varying degrees of liver dysfunction. The authors conclude that there is a slowed metabolism of caffeine in chronic liver disease due to a reduction in N3- and N7-demethylations affecting biotransformation through the paraxanthine pathway. It appears that the activity of the enzymes, belonging to the microsomal cytochrome P450 system, are proportionately lower in liver cirrhosis than in the activity of non-microsomal origin. The non-parallel decline in enzyme activities is not pronounced enough to increase the discriminating power of the caffeine elimination test in mild liver disease. 22583 [gas, hep] This study evaluated 40 healthy premenopausal women with autoimmune thyroiditis taking either physiologic doses of thyroid (which maintains a TSH in the normal range), or a suppressive dose (which puts it below the normal range). Compared to matched premenopausal volunteers with no history of thyroid dysfunction, a follow-up of 28 patients one year later revealed no difference in bone density, serum osteocalcin, parathyroid hormone and vitamin D and urinary cross-link excretion. A multivariate analysis of the whole group suggested that bone mineral density at the femoral neck and greater trochanter was related positively to weight and physical activity and negatively to thyroxine dose and patient age. At the lumbar spine bone mineral density was reduced non-specifically in the presence of thyroid disease and treatment, but this effect declined with increasing duration of therapy. A similar analysis of the patient group suggested that urinary cross-link excretion correlated positively with thyroxine dose and negatively with duration of treatment. Annualized changes in bone mineral density were inversely related to thyroxine dose at all sites but most significantly at the femoral neck and Ward's area. The authors did not find any effect of persistent historical TSH suppression on current bone; this might relate to the relative insensitivity of older TSH assays. Cross sectional and longitudinal data suggest that high daily doses of thyroxine in relation to the patient's body mass might adversely affect bone mass, particularly at the hip. These findings support the hypothesis that excessive exogenous thyroxine might deplete skeletal sites rich in cortical bone, such as in the femoral neck . 21920 [end] This study evaluated 58 sporadic medullary thyroid cancers for the place of origin and the place of residence and compared these cases with 408 other thyroid cancers of different histology who attended the same Endocrine Clinics in the Athens area. Clustering of sporadic medullary thyroid cancers were observed in the Ionian islands, where an increased incidence of familial cases had been observed. Patients with sporadic medullary thyroid cancers originated more frequently from rural areas where the main occupation was agriculture. It is possible that exposure to sunshine being greater in rural areas may be a factor, through vitamin D, which could be involved in the development of C-cell tumors in predisposed individuals. Geographical differences and the incidence of medullary thyroid cancer have been reported previously, such as a high incidence in Iceland and a low incidence in Scotland. There is no apparent explanation for the observed difference in the incidence of medullary thyroid cancers between villages and cities in the same country. One difference noted might be dietary habits, which were not evaluated in this study. 22670 [can] This study evaluated the profile of the anti-tetanus toxoid IgG subclasses in children receiving vitamin A supplementation, or a placebo, in order to assess the potential utility of the enhanced anti-tetanus toxoid response. In a randomized, double-blind, placebo-controlled clinical trial, the levels of the different anti-tetanus toxoid IgG subclasses were measured two weeks before and three weeks after immunization in 139 Indonesian preschool children between 3 and 6 years of age. Children who were given vitamin A prior to the immunization had significantly increased IgG1 levels, regardless of whether they were undergoing primary or memory reactions. In the group of children who underwent a secondary response to tetanus toxoid, vitamin A supplementation was associated with a modest, but significant, change in the level of anti-tetanus toxoid IgG3. The were only minor changes in the levels of anti-tetanus toxoid IgG2 and IgG4. Because IgG1 is a subclass that is associated with a protective response to tetanus toxoid immunization, these results suggest that vitamin A supplementation may be a safe and effective way to enhance the humoral response to tetanus toxoid and other vaccine antigens. 21784 [imm, inf] This article reviews the possibility of aluminum uptake from drinking water. Soluble aluminum is more bioavailable in the more potentially toxic form. The authors "gavaged" simulated tap water which contained low levels of radioactive soluble aluminum in the stomach of their animals. Accelerator mass spectrometry showed that trace amounts of aluminum from this single exposure directly entered their brain tissue. If a comparable amount of aluminum was taken up into the human brain from alum-treated drinking water over a prolonged period of time this might contribute to long term health consequences for some people. The authors conclude from this data that soluble aluminum is toxic to brain cells; alum treatment of a raw water source can substantially increase the level of bioavailable soluble aluminum in the Finnish drinking water supply; and aluminum is taken up into the brain of rats which have had 4 milliliters of simulated drinking water gavaged into the stomach. 22322 [neu] This article reviews the role of chemopreventive factors in the human diet. It is noted that diets containing abundant amounts of vegetables, fruits and grains can reduce the risk of several types of cancer, especially colon cancer. Eating vegetables and fruits is likely to reduce the consumption of fat or other more caloric foods. Calorie restriction by itself has been shown to reduce the incidence of cancer. Fruits and vegetables are excellent sources of antioxidants which include vitamins C, E, beta-carotene and flavonoids, which provide mechanisms of defense for removing or scavenging free radicals. Cruciferous vegetables contain dithiolthiones, thiocyanates, isothiocyanates, and sulforaphane, which are reported to have chemopreventive properties. These agents seem to stimulate the production of protective enzymes such as glutathione that detoxify carcinogens. Other elements in fruits and vegetables, such as polyphenols, folic acid, hemin, dietary calcium, dietary fiber, and chlorophyllin may enhance the benefits derived from these vegetables. Phenolic compounds found in grains can block the effect of carcinogens by inhibiting the formation of carcinogenic metabolites. Phenolic antioxidants have been found effective in reducing the incidence of neoplasms and preneoplastic lesions that have been chemically induced in rats. Other compounds in grains, specifically lignans, flavonoids and phytic acid may contribute to their overall chemopreventive effect. Atherogenic risk in hyperlipemic humans can be reduced by supplementing the diet with flaxseed which contains alpha-linolenic acid and fiber, and bread containing 10% flax. This results in a reduction of the serum total and low-density lipoprotein cholesterol and a decrease in platelet aggregation. Flavonoids are polyphenolic antioxidants that occur naturally in fruits, vegetables and in beverages such as tea and wine. Many of them are scavengers of free radicals, antioxidants, chelating agents, and modifiers of enzymatic and other biological functions. The best understood mechanism of flavonoids is their scavenging capacity of oxygen radicals. It is noted the beneficial effects of Ginko Biloba extract have been attributed to the flavonoids myrecetin and quercetin. In addition to its antioxidant properties, tumeric has been known to reduce urinary mutagens in smokers and promote mechanisms that enhance detoxification. Curcumin has been reported to inhibit cancer at the initiation, promotion and progression phases. D-limonene which is a natural constituent of many plants, especially citrus peel, dill weed oil and caraway oil, inhibits formation of carcinogen-induced mammary tumors in animals. The mechanism of its chemopreventive activity appears to be the induction of the detoxifying enzyme glutathione-S- transferase. Effective antioxidants have been found in spices and herbs like rosemary, sesame seed, oregano, chili pepper and ginger. Sesame, dad-lily, green tea, bamboo shoot, red date, and laver . . . which are natural foods commonly used in China . . . have been shown to lower the mutagenicity of aflatoxin B1. Selenium in the salt form appears to be one of the few inorganic chemopreventive substances. Isoflavones and phytoestrogens in soybeans may be the active antitumorogenic components responsible for the lower incidence of breast cancer among women in the Pacific Basin. Genistein is an isoflavonoid found in soy products that may have its chemopreventive effects by affecting angiogenesis. Garlic has considerable evidence supporting its anticancer effect. The chemopreventive potential of garlic in inhibiting tumorigenesis lies in the presence of organosulfur compounds such as diallylsulfide, diallydisulfide and diallylpolysulfides, thiosulfinates, sulfoxides, S-allylcysteine. Garlic powder may also lower blood pressure and serum levels of triglycerides and cholesterol. In one particular study, garlic powder at 3 X 300 mg tablets per day reduced LDL cholesterol by 11% while HDL cholesterol levels were unchanged. Another compound in garlic, ajoene, has been shown to reduce platelet aggregation as well as inhibit reactions by known agonists. Some components in tea, specifically green tea, are not only antimutagenic but also anticarcinogenic. Green tea was found to be protective against tobacco-specific nitrosamine-induced lung tumorigenesis in mice. There are beneficial effects of drinking green tea in relationship to serum cholesterol, lipids and blood pressure. Coffee appears to have some mutagens and some components possessing antimutagenic properties. Some of these components include chlorogenic acid, gallic acid, kahweol and cafestol. Many phenolic flavonoids in red wine have strong antioxidant effects. The phenolic compounds in red wine include catechins, epicatechin, quercetin, resveratrol, anthocyanins, and procyanidines. Red wine extract has been shown to inhibit the oxidation of LDL cholesterol. Antioxidant vitamins include vitamin C, E, and beta-carotene. Selenium stimulates the enzyme glutathione peroxidase which appears to have anticarcinogenic properties. It is noted that some scientists believe there is enough evidence from a number of small scale human studies to make general recommendations about such antioxidants as vitamin C, E, beta-carotene and selenium with regards to supplementation. It is still not well clarified whether the regular daily doses of antioxidant intake are sufficient only to avoid dietary deficiencies, while much larger doses are needed to provide the protective effects against cancer and other chronic diseases. Economic factors may enhance the utilization of certain antioxidants as cancer rates increase if it can be shown that chronic diseases such as cataracts, cardiovascular disease, some forms of cancer could be prevented by taking regular antioxidant supplementation. The cost of supplementing the diet of the general population with these antioxidants would be much cheaper and more appropriate than the treatment of the disease. For example; cataract surgery in the United States is 4 billion dollars a year, and the single biggest expense for Medicare. Yet studies have shown that vitamin C may be a preventive agent for cataract formation. The total cost in the United States associated with neoplastic disease is estimated to be more than 100 billion dollars in 1990. In Canada the economic cost of cardiovascular disease in 1986 was 16.8 billion dollars; in cancer, 9.1 billion. There is controversy remaining on whether to fortify regular foods with specific chemopreventers. Even before recommendations are made it appears that major health benefits for a wide segment of the population can be achieved by increasing the daily consumption of fruits and vegetables. 21396 [can, nut] This study evaluated the relationship of vaginal candidiasis and the potential reservoir from the gastrointestinal and rectal areas. Cultures for yeast were obtained from the mouth, rectum, vulva and vagina every 1 to 2 months for 1 year in these patients assessed. In 37 healthy controls 8.1% had yeast cultured from the vulva, vagina and rectum and 10.8% from the mouth. In 193 patients with vaginitis 98.4% had yeast cultured from the vagina, 55.4% from the vulva, 48.2% from the rectum and 26.9% from the mouth. During visits without vaginitis 10.1% had yeast cultured from the rectum, 11.6% from the vulva, 13.1% from the vagina and 15.2% from the mouth. Yeast in the lower bowel during symptomatic vaginitis is higher than in controls but not significantly greater during the asymptomatic period. Recurrence of candida vaginitis is not dependent on the yeast reservoir from the lower gastrointestinal tract between symptomatic episodes. These results suggest that the intestinal reservoir is not a likely source for the recurrence of vaginal candidiasis. Failure of oral nystatin or oral imidazole to prevent recurrences adds further proof to the findings that carriage of yeast in the lower gastrointestinal tract is probably not related to the pathogenesis of chronic, recurrent, vulvovaginitis. There may be mild cellular immunity impairment that is undetected. 21350 [gyn] Thirty gm per day of fish oil containing 60 I.U. of vitamin E was given to 11 healthy volunteers with normal fibrinogen and C- reactive protein levels. No effects were seen on basal levels of fibrinogen and C-reactive protein. The effect of vitamin E on fibrinogen, C-reactive protein and plasminogen activator inhibitor levels was evaluated in 20 healthy volunteers who received vitamin E which doubled in dose every 2 weeks from 25 to 800 I.U. per day for 12 weeks. No changes in fibrinogen, C- reactive protein and plasminogen activator inhibitor were actively seen. Short-term supplementation of fish oil and vitamin E do not appear to effect these acute phase reactants in healthy volunteers. 21823 [car] More than 79,000 women radiologic technologists were evaluated, there were 600 breast cancer cases identified. Each of the 528 eligible subjects with breast cancer were matched to 5 control subjects. These individuals had been certified as radiologic technologists for a mean of 29 years. Significant increased risk for breast cancer were associated with early age and menarche which was defined as less than 11 years of age, first-degree relative with a history of breast cancer, prior breast biopsy, alcohol consumption, which was greater than 14 drinks per week, thyroid cancer, hyperthyroidism, and residents in the northeastern United States. Jobs involving radiotherapy, radioisotopes or fluoroscopic equipment were not linked to breast cancer risk. Personal exposures to fluoroscopy or multi-film procedures were not associated. Use of birth control pills, postmenopausal estrogens or permanent hair dyes were not risk factors for breast cancer. Among women who worked more than 20 years the relative risk for breast cancer was 1.13. More than 50% of the reported breast cancer cases could be explained by established risk factors. Employment as a radiologic technologist was not found to increase the risk of breast cancer. The contribution of prolonged exposure to relatively low doses of ionizing radiation to breast cancer risk was too small to be detectable at this time. 22962 [can] This study estimated the cost follow-up among colorectal cancer patients treated with curative intent on the broad spectrum of surveillance strategies suggested in the literature. The Medicare charges varied widely for the 5 years of post treatment follow-up from a low of $561 to a high of $16,492. When Medicare-allowed charges were converted to a proxy for actual charges with the conversion ratio of 1.62 and the range was then between $910 to $26,717 dollars or a 28-fold difference in charges. The authors conclude that the charges varied across follow-up strategies with no indication that higher cost strategies increased survival or quality of life. 22667 [can] This study evaluated 33 males and 20 females with chronic hepatitis C virus and found that hepatitis C virus-related liver damage is highlighted by increased iron storage which possibly may be induced by the virus and elicits a free-radical-mediated peroxidation with subsequent steatosis and activation of glutathione turnover. Hepatitis C virus patients are at high risk of hepatocellular carcinoma and the possible role of increased liver iron storage and liver carcinogenesis. 22385 [gas, hep] This study evaluated 21 healthy females over a 10 day period to determine if iron absorption would be affected by calcium intake. The amount of calcium per day was 937 mg, consumed either mainly at breakfast and late evenings or more evenly in all meals. Approximately 30 to 50% more iron was absorbed when no milk or cheese was served with lunch or dinner. The authors suggest that a reasonable separation of iron and calcium intakes could improve iron nutrition. 21629 [nut, gas] External irradiation of the thyroid during childhood has shown in epidemiologic studies increased incidence of thyroid tumors. There was a long latency of these tumors. Irradiation by iodine 131 in adults does not seem to increase the risk of thyroid tumors but in children the data is too scarce to draw a conclusion. The risks following low dose radiation or protacted radiation exposure are still a matter of debate. 22761 [end] This is a case report of 2 siblings with atypical methylmalonic aciduria with progressive encephalopathy. Initial symptoms were failure to thrive and growth retardation during the first year of life. This progressed into severe mental retardation, microcephaly, dystonia, spasticity and cataracts. There was a lower amount of methylmalonic acid in the urine compared to the classical methylmalonic acidemia syndrome. This level was not reduced by vitamin B12 therapy at 1 mg intravenously or protein restriction. The primary defect in this particular type of methylmalonic aciduria was not discovered. 22936 [met, neu, oph] This study evaluated 97 postmenopausal women who were randomized to either a group that was provided with soy foods for 4 weeks or a control group that instructed to eat as usual. The percentage of vaginal superficial cells increased in 19% of those eating the diet compared with 8% of the controls. FSH and LH did not decrease significantly with dietary supplementation as hypothesized, nor did sex hormone binding globulin increase. There was little change in endogenous estradiol concentration or body weight during the diet. Women with large increases in urinary isoflavone concentrations were not more likely to show an estrogenic response than were women with more modest increases. On the basis of published estimates of phytoestrogen potency, a 4 week soy supplemented diet was expected to have an estrogenic effect on liver and pituitary in postmenopausal women, but the estrogenic effect was not seen. At most, there was a small estrogenic effect on vaginal cytology. 22678 [end] This is an editorial which reviews the silicone breast implant controversy and information to date. What is known about silicone breast implants is that fibrous capsule contracture occurs in about 70% of the cases two to four years after implantation. The rate of complications . . . which include breast pain, contracture, rupture, infection, implant migration requiring surgery . . . approaches 50% at 10 years. In a Mayo Clinic study, there was a 30% failure rate at 7.8 years. Rheumatologists have described a veritable array of symptoms in more than 1,000 patients with silicone breast implants. The syndrome includes the symptoms of arthralgia, myalgia, sicca complex, paresthesia, balance disturbance, night sweats, rashes, memory difficulty and fatigue. Autoantibodies to collagen and extracellular matrix proteins and abnormalities of cell-mediated immunity have been found in women with silicone implants and not in controls. There does not appear to be a serologic marker consistently associated with rheumatic disease in these patients. These findings suggest that silicone implants may cause immune dysfunction and rheumatic disease. Much information has been released in the court room. þResearch which showed adjuvant activity and other types of immune dysfunction was kept from the FDA in 1991; manufacturersþ memoranda containing information on silicone toxicity and immune reactions were labeled þPlease discard after readingþ þ. Proposed human studies were not done. Only through the court system has this information been released. Manufacturers have not provided data showing safety. The author notes that the FDAþs decision to ban the use of silicone implants except in controlled clinical studies was a reasonable one. More research into silicone-related disorders is required by a prospective controlled study. 21382 [rhe, sur] There is limited data on vitamin A's effect on the local mucosal immune system. The gastrointestinal tract contains the largest amount of mucosal immune mass approximating almost 50% of the body's total immune mass. The gut mucosal immune system is the first line of protection against the extensive amounts of antigens that come into the gastrointestinal tract. The gut mucosal immune system contains B and T cells, monocytes, macrophages and plasma cells. Vitamin A is a fat soluble vitamin which is absorbed with the help of bile acids. Normal serum levels of vitamin A (retinol) and its retinoid compounds are 40-50 ug/ml and 3-4 ng/ml respectively. Decreased serum vitamin A levels have been associated with an increased morbidity in children and increased tumor rate. The way that vitamin A affects the immune system intracellularly has not been determined. Retinol's specific functional role may be mediated by its metabolites which act as intracellular messengers. Several nuclear receptors for retinoic acid have been discovered giving a good explanation for retinol's effect on cell function. The author feels that the gut mucosal system is a prime target for researchers who are interested in nutrition and immunology. 21653 [imm] In investigating the Brown & Williamson and British American Tobacco Company research related to environmental tobacco smoke in the mid 1970s it was noted that the British American Tobacco Researchers appeared to have determined that side stream smoke produced irritation and it contains toxic substances including N- nitrosamines and that it is "biologically active" (eg, carcinogenic) in laboratory tests. During the 1980s, the primary purpose of the British American Tobacco Company research related to environmental tobacco smoke was to devise a new cigarette that omitted less irritating and less biologically active side stream smoke. Publicly the tobacco industry denies that exposure to environmental tobacco smoke has been proven dangerous to health. The tobacco companies has been critical of the methodology of research on environmental tobacco smoke. The tobacco industry has privately conducted internal research which has supported in part the conclusion that passive smoking is dangerous to health, while it has publicly denied that the hazards have been proven. 22890 [can, med] Eight hundred and fifty-eight nonfatal myocardial infarction cases in women between 45 and 69 years of age were compared to 858 controls for the relationship of coffee drinking. The risk of myocardial infarction increased with increasing number of cups of coffee among both drinkers of any type of coffee and drinkers of caffeine containing coffee only. For consumption of caffeine containing coffee alone the relative risk estimates were 5 to 6 cups, 7 to 9 cups, and 10 or more cups per day relative to less than 1 cup per day were 1.4, 2.1 and 2.5 respectively. There was no increase seen for fewer that 5 cups of coffee per day. The positive association with heavy coffee drinking was seen among nonsmokers as well as smokers. These results suggest that heavy coffee consumption increases the risk of myocardial infarction. 22269 [car] Five healthy subjects between 29 and 44 years of age without significant complaints were evaluated in this study. In one part of the study subjects were given intravenous saline injections, and in the other study they were given intravenous injections of methylcobalamin 10 ug/kg. The intravenous administration of methylcobalamin increased rectal temperature in the latter hours of the daytime during the constant routine. The activity did not change between the treatments in any period during the constant routine. During the later hours of constant routine, alertness assessed with visual analog scale was higher in the methylcobalamin group than in the placebo group. The period in which the drug treatment produced greater alertness almost coincided with that in which the methylcobalamin elevated rectal temperature. The findings for alertness together with those of the temperature rhythm suggests an effect of vitamin B12 on the circadian clock. 22674 [end, neu] This study found that within the first year of life, 12 of 46 cystic fibrosis patients had developed sodium chloride deficiency. Mean plasma sodium, potassium and chloride levels were 122.9, 2.5 and 73.3 mEq/l respectively. Alkalosis and elevated plasma renin activity were seen in all patients. Patients were treated with intravenous fluids and electrolyte solutions. All the patients were less than 7 months of age during their first attack; five received only breast milk and the others received breast milk and formula. Oral salt was supplemented at 2-4 mEq/kg per day. These patients may have a genetic predisposition towards high sodium losses. 21687 [gen, met] This article reviews the role of the larger amount of available iron in the diet of nonbreast fed infants as compared to those given human milk and the relationship to Sudden Infant Death Syndrome. Many studies have noted that Sudden Infant Death Syndrome is more frequent in nonbreast fed infants. Iron in nonbreast fed infants diets can permit the multiplication and toxigenisis of such pathogens as salmonella and clostridium. Excessive quantities of iron in formulas and supplements given to infants less than 6 months of age have been associated with an increased risk of salmonellosis, botulism and SIDS. Evidence is given for the effect of the relationship of increased iron on SIDS. An evaluation of 53 milk proprietary milk formulas sold in Europe and the United States and Japan revealed a range of iron concentrations between 3-1,050 uM. The highest quantities were contained in 6 U.S. formulas which had concentrations greater than 892 uM an amount 3 times higher than the maximal quantity recommended by nutritional scientists. During the first 6 months of postnatal, full term life, breast fed infants without supplemental iron developed neither iron deficiency anemia nor depletion of iron stores. It is well established that iron absorption from breast milk is more efficient than from these formulas. The author questions how prudent it is to add iron to formula for infants less than 6 months of age with as much as 155 times the quantity of iron that is present naturally in breast milk. 22201[nut, ped] This study 121,700 female nurses between 30 and 55 years of age who began the Nurses Health Study in 1976. In 1982 toenail clippings were requested from this cohort and 62,641 participants with no history of cancer returned toenail clippings. Over a 41 month follow-up period 503 cases of cancer other than breast cancer or nonmelanoma skin cancer were analyzed. No adverse association was seen between selenium levels in the toenails and cancer risk. Toenail selenium was not inversely associated with any cancer at any major site which included uterine and colorectal cancer, melanoma, ovarian cancer or lung cancer. There was a nonsignificant positive association observed at several sites. The authors concluded that toenail selenium levels were not inversely associated with cancer risk in the study. 22377 [can] This was a 98 day study evaluating 29 sedentary men with hypercholesterolemia between 38 and 70 years of age. After a 2 week adjustment period on a low-fat controlled diet the subjects were given either a low-fat controlled diet plus 20 gm of corn bran supplement or a low-fat controlled diet with 20 gm of wheat bran supplement. The low-fat diet significantly reduced all the lipid parameters except for HDL cholesterol. The corn fiber supplementation resulted in an additional lowering of serum cholesterol, triglyceride and VLDL-C concentrations. Serum LDL-C and HDL-C concentrations were not significantly altered by the corn fiber or the wheat fiber supplementation. The authors conclude that supplementing a low-fat diet with corn bran is an effective way of reducing serum lipid concentrations in men with hypercholesterolemia. 21599 [car, gas, nut] Twenty patients with long term sporadic Alzheimer's disease received vitamin supplementation of iron, B6 and coenzyme Q10. There was a significant improvement in a variety of mental and functional tests at one year. It is believed that coenzyme Q10 might reduce the free radicals formed by iron, and that B6 plays a role in neurotransmitter synthesis. The combination of these 3 may have a positive effect on reducing the signs and symptoms of Alzheimer's disease. 21436 [ger, neu, nut, psy] Bronchopulmonary dysplasia is a chronic lung disease that follows mechanical ventilation which necessitates supplemental oxygen beyond 1 month of age. It is clinically seen most frequently in premature births of 24 to 32 weeks gestation in infants whose breathing must be assisted mechanically. Mechanical ventilation causes pulmonary barotrauma and oxygen toxicity from chronic use of high concentrations of inspired oxygen. This results in stiffer, less compliant lungs and oxygen dependency. Difficulty in ventilating the infants produces chronic hypoxemia and hypercarbia. Undernutrition and poor linear growth are common findings in these infants. Insufficient energy intake reduces the ability to improve oxygenation and therefore slows respiratory muscle development to improve ventilatory effort. An interesting point is that all premature infants with bronchopulmonary dysplasia have functionally immature gastrointestinal tracts which may cause maldigestion. To meet this need, in some medical centers preterm milk is fortified to increase its energy, protein, and mineral content. Studies using fortified preterm human milk demonstrate normal growth in preterm infants, which is a growth that approximates the rate that is seen during the 3rd trimester of intrauterine life. Most premature infant formulas have a caloric density that is greater than that of preterm milk. Infants with bronchopulmonary dysplasia must have a formulation with a higher caloric density than other premature infants. Because energy deficits occur gradually, there must be constant and consistent monitoring of the infantþs energy needs, and an appropriate response in terms of the amount of formula delivered. Attention to this detail will provide the infant enough energy to prevail over the disease. 21477 [gas, ped, pul] This is an extensive review article on breast cancer prevention. Current preventive strategies include avoidance of breast irradiation particularly in adolescents, avoidance of cigarette smoking or passive smoke particularly in adolescents, avoidance of alcohol, avoidance of long duration lactation, avoidance of obesity later in life and prophylactic mastectomy. Breast cancer preventive interventions being evaluated in clinical trials include 4-hydroxyphenyl retinamide, tamoxifen and a low fat diet. Breast cancer approaches in the preclinical evaluation include pseudopregnancy, combination oral contraceptives, LHRH agonist hormonal oophorectomy, and modification of estrogen metabolism. Increased exercise and avoidance of excess calories, especially in adolescents, may delay the onset of menarche. Other preventative interventions being evaluated include growth factor control and ornithine decarboxylase inhibitors. Ornithine carboxylase suppression seems to be an integral part of the reversal of tumor promotion. Other ornithine decarboxylase inhibitors include retinoids and nonsteroidal antiinflammatory drugs. The author notes that the increasing incidence of postmenopausal breast cancer is frustrating and treatment gains have been limited. Progress and widespread prevention has been very slow and the multifactorial etiology of breast cancer development is mostly responsible for the delay. 22668 [can] Ten healthy subjects who swim regularly in ice cold water during the winter were evaluated before and after this short term whole body exposure. There was a drastic decrease in uric acid concentration seen during and following the exposure to cold stimulus. It is believed that the uric acid decrease is caused by its consumption after formation of free radicals. The level of oxidized glutathione and the ratio of oxidized glutathione/total glutathione increased after cold exposure. Baseline concentration of reduced glutathione was increased and the concentration of oxidized glutathione was decreased in the erythrocytes of winter swimmers as compared to those of non winter swimmers. This appears to be an adaptation to repeated oxidative stress. Hardening is the exposure to a natural stimulus, in this case thermal, which results in an increased tolerance to stress and disease. Exposure to repeated intensive short-term cold stimuli is often utilized in hydrotherapy, which is used in physical medicine for hardening. 21866 [met] This study of Harvard University Alumni evaluated 17,321 men mean age of 46 years and found a graded inverse relationship between total physical activity and morbidity. Vigorous activities but not nonvigorous activities were associated with longevity. Among those men who reported vigorous activity there were 259 deaths and among those who reported nonvigorous activity there was 380 deaths. Physical activity can improve cardiac, mechanical and metabolic function, reduce platelet aggregation and increase fibrinolytic activity. Sedentary individuals should increase their activity level to enhance longevity. Specifically vigorous activities were associated with greater longevity. The authors do note that even nonvigorous exercise is preferable to sedentariness. These findings were only pertinent to all cause mortality. It is noted that modest exercise can improve lipid and glucose profiles. 22245 [exe, ger] This study evaluated 9 nonsmoking men between 23 and 37 years of age regarding the association between exercise intensity and related oxidative stress. The subjects exercised 30 minutes at their aerobic and anaerobic thresholds. The researchers also tested the effect of oral N-acetylcysteine on exercise-associated rapid glutathione oxidation in the subjects performing 2 identical maximal bicycle ergometer exercise tests. Before the second test, the men took 200 mg 4 times per day of N-acetylcysteine tablets for 2 days and an additional 800 mg on the test morning. Blood samples were drawn before, immediately after and 24 hours after the tests. Total and oxidized glutathione levels in the blood were determined. Though there was an association between a single bout of exercise and leukocyte DNA damage, the study suggested that the parameters may not serve as a sensitive index to assess the role of exercise intensity and the extent of exercise-associated oxidative stress. Plasma thiobarbituric acid reactive substances did not change after the maximal bicycle ergometer exercise test or the same exercise test with N-acetylcysteine supplementation. N-acetylcysteine supplementation resulted in an increase in the pre-exercise net peroxyl radical scavenging capacity. Supplementation may have spared exercise-associated blood glutathione oxidation and thiol redox changes. N-acetylcysteine supplementation increased the net peroxyl scavenging capacity of the plasma, indicating that the antioxidant properties of the drug may enhance the net antioxidative capacity of the plasma. It is possible that exercise- associated changes of the blood glutathione redox status may be circumvented by supplementation with N-acetylcysteine. 22023 [exe, met] This study evaluated 820 women with breast cancer and 1548 controls. Vegetable and fruit consumption were independently associated with statistically significant reductions of breast cancer risk by 12 and 8% respectively. Increased olive oil consumption was associated with a significantly reduced risk to breast cancer, whereas increased margarine consumption was associated with a significantly increased risk. The association with olive oil was seen mostly among postmenopausal women. 21935 [can] Twenty patients with long term sporadic Alzheimer's disease received vitamin supplementation of iron, B6 and coenzyme Q10. There was a significant improvement in a variety of mental and functional tests at one year. It is believed that coenzyme Q10 might reduce the free radicals formed by iron, and that B6 plays a role in neurotransmitter synthesis. The combination of these 3 may have a positive effect on reducing the signs and symptoms of Alzheimer's disease. 21436 [ger, neu, nut, psy] Seven patients with bullous pemphigoid were given a regimen of 2 gm of Tetracycline combined with 2 gm of nicotinamide daily. There was total remission achieved within 6 to 8 weeks after which the dose was gradually tapered. The duration of therapy was approximately 7 months. The mode of action is unknown. Suppression of chemotaxis of neutrophils and eosinophils is thought to be important. Systemic steroids do not appear to clear the bullous eruptions more rapidly than this combination therapy or prevent relapses. This therapy should be considered as the treatment of choice for bullous pemphigus. 22867 [der] This study evaluated 28 subjects with the diagnosis of simple phobia compared to 30 normal controls who were subjected to a 35% carbon dioxide panic provocation. The phobic patients reacted more strongly to the challenge of carbon dioxide than the contro7ls. This increase in anxiety was comparable to the increase of anxiety of panic disorder patients from other studies. The authors conclude that there is a constitutional þpredispositionþ that may lead to panic disorder and to the development of specific phobias. Through a self-administering apparatus subjects received, in a random order, a 7-vital-capacity breath of 35% C02/65% 02 mixture and an 80% N2/20% O2 mixture. Between the 2 inhalations the subjects had a 15 minute break outside the laboratory. It appears possible to use this test to help understand the underlying mechanisms in different anxiety disorders. 21480 [psy]7 This study evaluated 60 patients with sporadic colonic adenomas in a double-blind trial receiving 2.5, 5.1 or 7.7 gm of fish oil per day or a placebo for 30 days. In another study 15 patients with polyps received 2.5 gm of fish oil per day. Main proliferative indices and mucosal arachidonic acid levels were significantly decreased in all the treated groups, whereas mucosal eicosapentaenoic acid and docosahexaenoic acid levels increased. Significantly reduced proliferation was seen only in patients with abnormal baseline patterns. These effects lasted during long term low dose treatment. There was a temporary reduction in mucosal vitamin E levels observed after 1 month of treatment. The authors conclude that low dose fish oil supplementation has short and long term benefits on abnormal rectal proliferation patterns associated with increased risk to colon cancer. The authors conclude that low dose omega-3 fatty acid supplementation appears to improve abnormal rectal epithelial cell proliferation patterns in patients at risk for colon cancer and this can be maintained by long term treatment. Whether these proliferative patterns in other segments of the colon are equally effected by fish oil supplementation has not been determined. These results showed that rectal mucosal vitamin E levels are not chronically depleted by this treatment. Yet it still may be advisable to increase vitamin E intake during fish oil administration. 21429 [can, gas] In evaluating over 21,000 children who were visited every 4 months over 2 years and in a morbidity study of 1,455 children who were visited weekly for 1 year, there was no difference between the children supplemented with vitamin A and those who were given a placebo in malaria mortality rates or fever incidence based on reported symptoms. There was no correlation between serum retinol at the beginning of the trial and subsequent malaria parasitemia in children receiving placebo. Vitamin A supplementation had no effect on malaria in this population. 22101 [inf] Three group of patients were evaluated: 18 patients subjected to thrombolytic therapy within 6 hours after the onset of myocardial infarction; 16 patients with coronary artery disease without a history of previous myocardial infarction; and 50 healthy volunteers divided into 2 subgroups according to age. There was modification of zinc, copper, selenium and iron metabolism that followed thrombolysis. Of major importance was the decrease in zinc and iron, an increase in copper, and the stabilization at low levels for selenium. Monitoring essential trace elements could be of great interest for prognosis following thrombolysis after an acute myocardial infarction. 22031 [car] This study evaluated 22 preeclamptic women and 40 normotensive women for polyunsaturated fatty acid status. After adjusting for variables, women with the lowest level of omega-3 fatty acids were 7.6 times more likely to develop preeclampsia as compared to those women with the highest level of omega-3 fatty acids. A 15% increase in the ratio of omega-3 and omega-6 fatty acids was associated with a 46% reduction in risk of preeclampsia. Low levels of omega-3 fatty acids and high levels of omega-6 fatty acids, particularly arachidonic acid, appeared to be associated with an increased risk of preeclampsia. The data suggests that dietary consumption of omega-3 fatty acids, which is provided in fish oil, can alter eicosanoid metabolism which tends to favor vasodilation. The chemical roles of omega-3 fatty acids in reducing circulating triglycerides and decreasing platelet and leukocyte reactivity, as well as their ability to reduce blood pressure and increase utero placental perfusion, are consistent with this observation. 22650 [obs] Sources of lead exposure to children include lead based paint, lead contaminated soil, house dust, food and drinking water, leaded gasoline, parental occupations and hobbies, industrial emissions, lead-glazed ceramicware, lead-solder cans and some traditional medicines and cosmetics. Ingestion is a primary route of exposure to children. A survey of 43 directors of medical school affiliated lead clinics located in 18 cities concluded that: 1. There is a wide range of blood lead levels for which chelation therapy is recommended. 2. The majority of children with blood lead levels of 1.21 umol/l to 2.17 umol/l (25 ug/dl to 45 ug/dl) with negative CaEDTA provocation tests do not receive chelation therapy. Oral chelating agents are used in the minority of clinics. There is no common approach for the treatment of lead toxicity as present. In the majority of pediatric centers current management of blood lead elevation did not appear to reflect the new information regarding the effects and treatment of lead poisoning. It is noted that meso- 2,3-dimercaptosuccinic acid (succimer) is a promising new oral treatment for lead poisoning. Succimer is a chemical analog of British antilewisite that forms water soluble complexes with lead that are excreted by the kidneys. Succimer is