Published Science

The aim of this investigation was to evaluate the environmental exposure to Pb and Cd during 1990-1997 of inhabitants of Katowice District, which is an area of high environmental exposure to lead and cadmium, as well as exposure to Fe, Zn, Cu, Mn, Ni, Cr, Ca, Na, and K, on the basis of concentrations in hair, teeth, and nails. This investigation was to explain if accumulation of Pb and Cd can affect the concentration of such essential metals as Fe, Zn, Cu, and Ca. Inhabitants of the Beskid area constituted a control group. Analysis of the aforementioned elements was carried out on 624 hair samples, 785-tooth- samples, and 338 nail samples taking into consideration sex, age (30 years), and type of teeth (incisor, canine, molar, premolar). Concentrations of elements in the media investigated were determined using atomic absorption spectroscopy. The results were calculated using the Statistica program. The major statistical analysis focuses on determining analysis of variance by MANOVA/ANOVA, Rao R (P

BACKGROUND: Dietary intakes and nutrient status were compared in meat-eaters and non-meat-eaters from the National Diet and Nutrition Survey of children aged 1.5-4.5 years. METHODS: Children (n = 1351) were categorized as 'omnivores' or 'vegetarians', according to whether they consumed meat or meat products during a 4-day dietary record. Blood samples were also obtained for analysis of haematological and biochemical nutrient status. RESULTS: Three per cent of children were 'vegetarian'. They consumed higher proportions of milk and milk products, although this was significant only in older children (P = 0.007), owing to high consumption by the high proportion of Asian children. In vegetarians, energy intakes tended to be lower in both age groups. Percentage energy from protein and fat were lower, while that from carbohydrate was higher compared with omnivores. Cholesterol intakes were lower, significantly so for younger children (P < 0.001). Intakes of micronutrients were either higher (vitamins C and E, potassium) or lower (niacin and sodium) in younger vegetarians compared with omnivores. Energy-adjusted intakes of iron and zinc did not differ significantly from those of omnivores, although both intakes were low in many children (6-20%

BACKGROUND: The effects of a prolonged low-carbohydrate diet rich in n-3 fatty acids on blood lipid profiles have not been addressed in the scientific literature. OBJECTIVE: This study examined the effects of an eight-week ketogenic diet rich in n-3 fatty acids on fasting serum lipoproteins and postprandial triacylglycerol (TG) responses. DESIGN: Ten men consumed a low-carbohydrate diet rich in monounsaturated fat (MUFA) and supplemented with n-3 fatty acids for eight weeks. Fasting blood samples were collected before and after one week of habitual diet and on two consecutive days after 2, 4, 6 and 8 weeks of the intervention diet. Postprandial TG responses to a fat-rich test meal were measured prior to and after the intervention diet. RESULTS: Compared to the habitual diet, subjects consumed significantly (p

Gallic acid is one of the main phenolic components of black tea. The objective of this study was to identify urinary gallic acid metabolites with potential for use as markers of black tea intake. In an initial study, nine compounds, assessed by using gas chromatography-mass spectrometry, were found to increase in concentration in urine after 3 cups of black tea over 3 h. A subsequent study employed a controlled crossover design in which 10 subjects consumed 5 cups per day of black tea or water for 4 weeks in random order. Twenty-four hour urine samples were collected at the end of each period. Of the 9 candidate compounds identified in the initial study, only 3 were present at higher concentrations in urine of all 10 subjects during tea-drinking in comparison to water-drinking periods. These compounds were identified as 4-O-methylgallic acid, 3-O-methylgallic acid, and 3, 4-O-dimethylgallic acid, all methyl ether derivatives of gallic acid. It is suggested that these compounds have the potential to be used as markers of black tea intake.

Epidemiological studies have shown an increased incidence of coronary artery disease in patients with chronic infections and inflammatory disorders. Because oxidative modification of lipoproteins plays a major role in atherosclerosis, the present study was designed to test the hypothesis that the host response to infection and inflammation induces lipoprotein oxidation in vivo. Lipoprotein oxidation was measured in 3 distinct models of infection and inflammation. Syrian hamsters were injected with bacterial lipopolysaccharide (LPS), zymosan, or turpentine to mimic acute infection, acute systemic inflammation, and acute localized inflammation, respectively. Levels of oxidized fatty acids in serum and lipoprotein fractions were measured by determining levels of conjugated dienes, thiobarbituric acid-reactive substances, and lipid hydroperoxides. Our results demonstrate a significant increase in conjugated dienes and thiobarbituric acid-reactive substances in serum in all 3 models. Moreover, LPS and zymosan produced a 4-fold to 6-fold increase in conjugated diene and lipid hydroperoxide levels in LDL fraction. LPS also produced a 17-fold increase in LDL content of lysophosphatidylcholine that is formed during the oxidative modification of LDL. Finally, LDL isolated from animals treated with LPS was significantly more susceptible to ex vivo oxidation with copper than LDL isolated from saline-treated animals, and a 3-fold decrease occurred in the lag phase of oxidation. These results demonstrate that the host response to infection and inflammation increases oxidized lipids in serum and induces LDL oxidation in vivo. Increased LDL oxidation during infection and inflammation may promote atherogenesis and could be a mechanism for increased incidence of coronary artery disease in patients with chronic infections and inflammatory disorders.

Serum thyroid hormone concentrations and their metabolic fate are within the normal range limits in obese subjects. Also serum TSH concentrations and its response to TRH are normal, suggesting that tissue availability of thyroid hormones is normally preserved in these subjects. In contrast, during caloric restriction serum T3 concentrations decrease as a consequence of its reduced production rate from peripheral deiodination of T4. Opposite, serum rT3 concentrations markedly increase as a result of its decreased metabolic clearance rate. During caloric overfeeding serum T3 concentration increase whereas serum rT3 concentrations decrease. In this condition the production rate of T3 increases. During caloric restriction and overfeeding serum T4 concentrations and its production and degradation are not modified.

2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is the most abundant heterocyclic amine carcinogen in the human diet and is a colon carcinogen in the rat. N-Acetyltransferase-2 (NAT2) catalyzes the conversion of PhIP and other heterocyclic amines to a DNA-reactive form. NAT2 has a polymorphic distribution in humans and other mammals, including rats. The rapid NAT2 genotype has been shown to be associated with increased colorectal cancer risk in some, but not all, human epidemiological studies. This investigation was designed to study the role of acetylator genotype in PhIP-induced colon carcinogenesis using aberrant crypt foci (ACF) as an intermediate biomarker. Five-week-old male, rapid-acetylator Fischer 344 (F344) rats and slow-acetylator Wistar-Kyoto (WKY) rats were fed the semipurified AIN76A diet with 0.01% PhIP, 0.04% PhIP, or no PhIP (control) for 8 weeks. PhIP induced ACF in both rapid- and slow-acetylator rats; 0.04% PhIP induced more ACF than 0.01% PhIP. There was no difference in the number of ACF between rapid- and slow-acetylator rats that were fed 0.01% PhIP. However, 0.04% PhIP induced 2-fold higher ACF and a greater dose-dependent increase in PhIP-induced ACF in the rapid-acetylator F344 rats compared with the slow-acetylator WKY rats. The results support human epidemiological studies showing higher risk for colorectal cancer in rapid acetylators who frequently consume meat that is very well done.

OBJECTIVE: To assess food behaviour and determine nutritional intakes of various vegetarian populations in France. DESIGN: A five-day self-administered food record which was mailed to members of the three principal French vegetarian organisations. SUBJECTS: 145 subjects, aged 7-87 y; 94 classical vegetarians (19% of those contacted), 34 Hindu lactovegetarians (17% of those contacted) and 17 macrobiotic (34% of those contacted). SETTING: The survey was conducted between March 1997 and July 1997 in France. RESULTS: Vegetarianism in France is represented by three main classes of food behaviour: ovolactovegetarian (AAV), lactovegetarian (KRI) and macrobiotic (MMK). The geometric mean intakes ranged from 1952 kcal/d (KRI), 2051 kcal/d (MMK) to 2384 kcal/d (AAV) for males and from 1302 kcal/d (MMK), 1675 kcal/d (AAV) to 1804 kcal/d (KRI) for females, after adjusting for age and BMI. The energy consumption in the MMK group was significantly lower than that in the AAV (P<0.05) and KRI groups (P<0.01), respectively. A difference among groups was observed for females (P=0.0002), but not for males. The MMK group consumed less lipid than the other two vegetarian groups, 46 g/d for men and 38 g/d for women vs 80 g/d for men and 61 g/d for women in the AAV group and 93 g/d for men and 81 g/d for women in the KRI group, respectively. Differences with AAV and MMK were statistically significant (P<0.001 for men and women for both groups). Mean protein consumption ranged from 60 g/d (AAV), 64 g/d (KRI) to 77 g/d (MMK) for males and from 46 g/d (MMK), 50 g/d (AAV) to 58 g/d (KRI) for females. Mean carbohydrate intakes ranged from 247 g/d (AAV), 321 g/d (KRI) to 338 g/d (MMK) in males and from 209 g/d (MMK), 228 g/d (AAV) to 242 g/d (KRI) in females. There were no significant differences in protein and carbohydrate intakes between the groups. Median calcium intakes ranged from 758.2 mg/d (MMK), 863 mg/d (AAV) to 989.3 mg/d (KRI) for the men and from 500.8 mg/d (MMK), 863 mg/d (AAV) to 934 mg/d (KRI) for the women. In the men, there was no differences in daily calcium intakes between the three vegetarian groups. However, we found a significant difference for women (P=0. 0041). The women in the MMK group presented significantly lower daily calcium intakes than the women in the AAV (P=0.013) and KRI (P=0.0032) groups. The AAV and KRI groups consumed dairy products supplying respectively 36% and 53% for the men and 39% and 59% for the women of total calcium against 0% for men and women in the MMK group. Median iron intakes ranged between 12.5 mg/d (KRI), 13.2 mg/d (AAV) and 22.5 mg/d (MMK) for the men and between 11.2 mg/d (KRI), 14.6 mg/d (AAV) and 16.9 mg/d (MMK) for the women. MMK (men P=0.0172 and women P=0.0131) and AAV (only in men P=0.037) groups consumed significantly higher quantities of iron than did the KRI group. The heme iron median intake in males and females of the three vegetarian groups was very low (

Cholelithiasis is the primary expression of obesity in the hepatobiliary system. In obese subjects the risk of developing gallstones is increased due to a higher cholesterol saturation of gall-bladder bile. During weight reduction with very low calorie diets (VLCD) the incidence of gallstones increases, but the mechanism for gallstone formation is not completely understood and several pathogenetic mechanisms have been suggested: increased saturation of bile, increased gall-bladder secretion of mucin and calcium, increased presence of prostaglandins and arachidonic acid. Alterations in gall-bladder motility may contribute to gallstone formation, but few studies have addressed the issue of gall-bladder motility during rapid weight loss and its possible role in gallstone formation. VLCD have been associated with a gall-bladder stasis, as a consequence of reduced gall-bladder stimulation by low fat content of the diets. A threshold quantity of fat (10 g) has been documented to obtain efficient gall-bladder emptying. Ursodeoxycholic acid administered during VLCD seems to have a protective role in developing a biliary cholesterol crystals. Gall-bladder emptying was lower in response to low fat meals with respect to relative higher fat meals, before as well as during the VLCD. This may account the possibility of an adaptative response of the gall-bladder motility to a given diet regimen. Adequate fat content of the VLCD may prevent gallstone formation, maintaining adequate gall-bladder motility and may be more economic and physiologically acceptable than administration of a pharmacological agent.

Posttraumatic stress disorder (PTSD) is a common reaction to traumatic events. Many people recover in the ensuing months, but in a signi®cant subgroup the symptoms persist, often for years. A cognitive model of persistence of PTSD is proposed. It is suggested that PTSD becomes persistent when individuals process the trauma in a way that leads to a sense of serious, current threat. The sense of threat arises as a consequence of: (1) excessively negative appraisals of the trauma and/or its sequelae and (2) a disturbance of autobiographical memory characterised by poor elaboration and contextualisation, strong associative memory and strong perceptual priming. Change in the negative appraisals and the trauma memory are prevented by a series of problematic behavioural and cognitive strategies. The model is consistent with the main clinical features of PTSD, helps explain several apparently puzzling phenomena and provides a framework for treatment by identifying three key targets for change. Recent studies have provided preliminary support for several aspects of the model. # 2000 Elsevier Science Ltd. All rights reserved.

BACKGROUND: The concept of a body weight set point, determined predominantly by genetic mechanisms, has been proposed to explain the poor long-term results of conventional energy-restricted diets in the treatment of obesity. OBJECTIVE: The objective of this study was to examine whether dietary composition affects hormonal and metabolic adaptations to energy restriction. DESIGN: A randomized, crossover design was used to compare the effects of a high-glycemic-index (high-GI) and a low-glycemic-index (low-GI) energy-restricted diet. The macronutrient composition of the high-GI diet was (as percent of energy) 67% carbohydrate, 15% protein, and 18% fat and that of the low-GI diet was 43% carbohydrate, 27% protein, and 30% fat; the diets had similar total energy, energy density, and fiber contents. The subjects, 10 moderately overweight young men, were studied for 9 d on 2 separate occasions. On days -1 to 0, they consumed self-selected foods ad libitum. On days 1-6, they received an energy-restricted high- or low-GI diet. On days 7-8, the high- or low-GI diets were consumed ad libitum. RESULTS: Serum leptin decreased to a lesser extent from day 0 to day 6 with the high-GI diet than with the low-GI diet. Resting energy expenditure declined by 10.5% during the high-GI diet but by only 4.6% during the low-GI diet (7.38 +/- 0.39 and 7.78 +/- 0.36 MJ/d, respectively, on days 5-6; P = 0.04). Nitrogen balance tended to be more negative, and energy intake from snacks on days 7-8 was greater, with the high-GI than the low-GI diet. CONCLUSION: Diets with identical energy contents can have different effects on leptin concentrations, energy expenditure, voluntary food intake, and nitrogen balance, suggesting that the physiologic adaptations to energy restriction can be modified by dietary composition.

Gluconeogenesis (GNG), a key metabolic process, involves the formation of glucose and glycogen from non-glucose precursors via pyruvate. In the strict sense, it also includes the contribution of glycerol as well as recycled glucose carbon (Cori's cycle). The developmental expression of GNG in the fetus and newborn and the quantitative contribution of GNG to glucose has been extensively investigated in humans and other mammalian species. Data from studies in rodents, rabbits, and sheep fetuses show that the development of GNG is a well-orchestrated process that is regulated by the expression of specific factors involved in the transcription of the genes for specific regulating enzymes, which catalyze GNG. These transcription factors and the genes for gluconeogenic enzymes are expressed at specific time periods during development. Although the fetus has the potential for GNG, the actual formation of glucose from pyruvate is not apparent until after birth because the rate limiting enzyme phosphoenolpyruvate carboxykinase appears only after birth in the immediate newborn period. Several tracer isotope methods have been employed to quantify the contribution of GNG to glucose. Of these, the recently developed stable isotope techniques with deuterium labeled water and the mass isotopomer distribution analysis appear to be the most precise and easily applicable in human studies. The available data show that in the human newborn, GNG appears soon after birth and contributes 30% to 70% to glucose produced. Application of new molecular biology techniques, in combination with sensitive tracer isotopic methods, will allow us to identify and examine metabolic disorders that impact GNG and help develop intervention strategies.

We describe a case of methylmalonic aciduria (MMA) occurred in a 22-month-old boy whose diet was exclusively based upon breast-feeding from a mother following a long-lasting strict vegetarian diet. Clinical picture showed a dramatic onset, with a profound drowsiness associated with a severe metaboli …

PURPOSE: Noninvasive assessment of bone mineral density, geometrical and biomechanical properties in premenopausal women with dietary intake of phytoestrogens and comparison of these parameters with those of age-matched female subjects with "Mediterranean" dietary intake lacking in these substances. MATERIAL AND METHODS: Volumetric cortical, trabecular and total mineral density and bone geometrical properties were evaluated in 15 female subjects with phytoestrogens dietary intake. Peripheral quantitative Computed Tomography (pQCT) was used to make measurements at the distal radius of the nondominant forearm. Fifteen age-matched subjects with "Mediterranean" dietary intake were chosen as a control group. Cross-sectional area (Total A), trabecular area (TA), cortical area (CA), cortical thickness (CThk) and strength strain index (SSI) were assessed as biomechanical parameters. RESULTS: Daily consumption of phytoestrogens was significatively different in the two groups (phy: 17.45 mg/die vs ctr: 0.35; p

Albumin synthesis was calculated in healthy male volunteers consuming diets differing in the relative contribution of protein from animal or vegetable sources. In one study (Study 1, n = 4) two isoenergetic and isonitrogenous diets were consumed for a period of 10 d each. One diet (diet A) was animal protein rich (74%), the other one (diet V) contained 67% of vegetable protein. Albumin synthesis rate was measured from L-[(2)H(5)]phenylalanine incorporation (43 mg/kg) at the end of each dietary period. Both albumin fractional synthesis rate (FSR) (5.7 +/- 0.6 vs. 6.7 +/- 0. 8%/d, P = 0.04) and absolute synthesis rate (ASR) (123 +/- 6 vs. 143 +/- 8 mg. kg(-1). d(-1), P = 0.05) were reduced after diet V. In a second study (Study 2, n = 8) a third dietary treatment was added (Diet VS). This was similar to diet V but supplemented with soy protein (18g/d). The results of study 2 confirmed that albumin synthesis was reduced after diet V (FSR: 5.9 +/- 0.3 vs. 6.7 +/- 0. 5%/d, P = 0.015; ASR: 126 +/- 7 vs. 146 +/- 9 mg. kg(-1). d(-1), P = 0.007), but it also showed that the drop could be prevented by adding supplemental protein to the predominantly vegetarian diet (Diet VS) (FSR: 6.4 +/- 0.3%/d, P = 0.08; ASR: 140 +/- 7 mg. kg(-1). d(-1), P = 0.03). Albumin synthesis appears to be modulated by changes in the proportion of animal vs. vegetable protein occurring in the diet. The mechanism might be related to differences in digestibility and consequently in net amino acid availability between diets.

BACKGROUND: The purpose of this article is to evaluate the impact of low protein and high fiber intakes on risk factors of stone recurrence in idiopathic calcium stone formers (ICSFs). METHODS: Ninety-six ICSFs were randomly assigned a low animal protein diet ( 25 g/day), or a usual diet (control group); all patients were recommended to increase their fluid intake. Their daily urine compositions were analyzed at baseline and at four months. Compliance with dietary recommendations was checked by validated food frequency questionnaires. Compliance with total and animal protein intakes was assessed by 24-hour urea and sulfate outputs, respectively. The nutritional intervention (oral instructions, written leaflet, phoning) and food assessment were carried out by a research dietitian. RESULTS: At baseline, diets and the daily urine composition did not differ between the three groups. At four months, while diets differed significantly, the 24-hour output of calcium and oxalate did not differ significantly within and between groups after adjustment for potential confounders (age, sex, and personal and family history of calcium stones) and baseline values. However, as many as 12 out of 31 ICSFs (95% CI, 22 to 58%) assigned to a low animal protein diet achieved a reduction in the urine urea excretion rate of more than 50 mmol/day and also exhibited a significant decrease in urinary calcium excretion that averaged 1.8 mmol/day. A significant correlation between urea and calcium outputs was observed only among patients with hypercalciuria. CONCLUSIONS: These results show that only ICSFs who markedly decrease their animal protein intake, especially those with hypercalciuria, can expect to benefit from dietary recommendations.

Both anthropologists and nutritionists have long recognized that the diets of modern-day hunter-gatherers may represent a reference standard for modern human nutrition and a model for defense against certain diseases of affluence. Because the hunter-gatherer way of life is now probably extinct in its purely un-Westernized form, nutritionists and anthropologists must rely on indirect procedures to reconstruct the traditional diet of preagricultural humans. In this analysis, we incorporate the most recent ethnographic compilation of plant-to-animal economic subsistence patterns of hunter-gatherers to estimate likely dietary macronutrient intakes (% of energy) for environmentally diverse hunter-gatherer populations. Furthermore, we show how differences in the percentage of body fat in prey animals would alter protein intakes in hunter-gatherers and how a maximal protein ceiling influences the selection of other macronutrients. Our analysis showed that whenever and wherever it was ecologically possible, hunter-gatherers consumed high amounts (45-65% of energy) of animal food. Most (73%) of the worldwide hunter-gatherer societies derived >50% (> or =56-65% of energy) of their subsistence from animal foods, whereas only 14% of these societies derived >50% (> or =56-65% of energy) of their subsistence from gathered plant foods. This high reliance on animal-based foods coupled with the relatively low carbohydrate content of wild plant foods produces universally characteristic macronutrient consumption ratios in which protein is elevated (19-35% of energy) at the expense of carbohydrates (22-40% of energy).

BACKGROUND: Plasma homocysteine levels have been directly associated with cardiac disease risk. Current research raises concerns as to whether comprehensive lifestyle approaches including a plant-based diet may interact with other known modulators of homocysteine levels. METHODS: We report our observations of homocysteine levels in 40 self-selected subjects who participated in a vegan diet-based lifestyle program. Each subject attended a residential lifestyle change program at the Lifestyle Center of America in Sulphur, Oklahoma and had fasting plasma total homocysteine measured on enrollment and then after 1 week of lifestyle intervention. The intervention included a vegan diet, moderate physical exercise, stress management and spirituality enhancement sessions, group support, and exclusion of tobacco, alcohol, and caffeine. B vitamin supplements known to reduce blood homocysteine levels were not provided. RESULTS: Subjects' mean homocysteine levels fell 13%: from 8.66 micromol/L (SD 2.7 micromol/L) to 7.53 micromol/L (SD 2.12 micromol/L; P

OBJECTIVE: Young adults frequently experiment with vegetarian and weight-loss diets. Comparisons of their experiences on these two different diets may help in the development of approaches to improve long-term adherence to weight-loss regimens. In the current study vegetarian and weight-loss diets were compared on how long and how strictly they were followed, and reasons why they were initiated and discontinued. RESEARCH METHODS AND PROCEDURES: From 428 college students surveyed, four groups were delineated: 1) 59 participants had been following a vegetarian diet but not a weight-loss diet (Vegetarian), 2) 117 participants had tried a weight-loss diet but not a vegetarian diet (Weight Loss), 3) 133 participants had followed both a vegetarian and a weight-loss diet (Both), and 4) 119 participants had not tried either diet (Neither). RESULTS: Differences were examined by comparing the Vegetarian and Weight-Loss groups as well as by comparing the two diets within the Both group. Duration of the vegetarian diet was much greater than the weight-loss diet; most participants in the Vegetarian group (62%) remained on their diet for more than 1 year, whereas the majority of the Weight-Loss participants (61%) followed their diet for 1 to 3 months. Similar results were found when comparing the two diets within the Both group. How strictly the two diets were followed, however, did not differ. Analyses revealed that reasons for discontinuing a diet varied; participants were more likely to cite boredom as a reason for discontinuing a weight-loss diet than a vegetarian diet (53% vs. 5% between groups and 30% vs. 10% within the Both group). DISCUSSION: The longer duration of the vegetarian diet relative to the weight-loss diet warrants further investigation. Results could possibly be applied to behavioral weight-loss treatment to improve long-term maintenance.

Background: A growing body of preclinical research suggests that brain glutamate systems may be involved in the pathophysiology of major depression and the mechanism of action of antidepressants. This is the first placebocontrolled, double-blinded trial to assess the treatment effects of a single dose of an N-methyl-D-aspartate (NMDA) receptor antagonist in patients with depression. Methods: Seven subjects with major depression completed 2 test days that involved intravenous treatment with ketamine hydrochloride (.5 mg/kg) or saline solutions under randomized, double-blind conditions. Results: Subjects with depression evidenced significant improvement in depressive symptoms within 72 hours after ketamine but not placebo infusion (i.e., mean 25-item Hamilton Depression Rating Scale scores decreased by 14 Ϯ SD 10 points vs. 0 Ϯ 12 points, respectively during active and sham treatment). Conclusions: These results suggest a potential role for NMDA receptor-modulating drugs in the treatment of depression. Biol Psychiatry 2000;47:351–354 © 2000 Society of Biological Psychiatry

Cholesterol- and cholesteryl ester-rich macrophage foam cells, characteristic of atherosclerotic lesions, are often generated in vitro using oxidized low density lipoprotein (OxLDL). However, relatively little is known of the nature and extent of sterol deposition in these cells or of its relationship to the foam cells formed in atherosclerotic lesions. The purpose of this study was to examine the content and cellular processing of sterols in OxLDL-loaded macrophages, and to compare this with macrophages loaded with acetylated LDL (AcLDL; cholesteryl ester-loaded cells containing no oxidized lipids) or 7-ketocholesterol-enriched acetylated LDL (7KCAcLDL; cholesteryl ester-loaded cells selectively supplemented with 7-ketocholesterol (7KC), the major oxysterol present in OxLDL). Both cholesterol and 7KC and their esters were measured in macrophages after uptake of these modified lipoproteins. Oxysterols comprised up to 50% of total sterol content of OxLDL-loaded cells. Unesterified 7KC and cholesterol partitioned into cell membranes, with no evidence of retention of either free sterol within lysosomes. The cells also contained cytosolic, ACAT-derived, cholesteryl and 7-ketocholesteryl esters. The proportion of free cholesterol and 7KC esterified by ACAT was 10-fold less in OxLDL-loaded cells than in AcLDL or 7KCAcLDL-loaded cells. This poor esterification rate in OxLDL-loaded cells was partly caused by fatty acid limitation. OxLDL-loaded macrophages also contained large (approximately 40-50% total cell sterol content) pools of oxidized esters, containing cholesterol or 7KC esterified to oxidized fatty acids. These were insensitive to ACAT inhibition, very stable and located in lysosomes, indicating resistance to lysosomal esterases. Macrophages loaded with OxLDL do not accumulate free sterols in their lysosomal compartment, but do accumulate lysosomal deposits of OxLDL-derived cholesterol and 7-ketocholesterol esterified to oxidized fatty acids. The presence of similar deposits in lesion foam cells would represent a pool of sterols that is particularly resistant to removal.

Contrary to earlier views the main oxidation products of low-density lipoprotein (LDL) are derived from linoleic acid and not arachidonic acid, as determined by GC/MS investigations of the in vitro oxidation of LDL samples. A similar product spectrum, in which epoxyhydroxyoctadecenoic acids such as 1 and 2 have been identified for the first time, is obtained from minimally oxidized (that is, aged) LDL. Since this is still recognized by the LDL receptor, it is concluded that toxic oxidation products are introduced in endothelial cells in vivo and cause damage there.

The present study was designed to establish a dose-response relationship for the efficacy of the ketogenic diet (KD). Sprague-Dawley rats were fed ketogenic diets containing varying ratios of fats; (carbohydrates + proteins) whereas control animals were fed rodent chow. Unless otherwise indicated, all animals were fed calorie-restricted, isocaloric diets beginning at P37 and ketonemia, seizure threshold and neurotoxic effects were determined. Despite being provided isocaloric quantities, animals fed lower ketogenic ratios gained weight relative to those fed diets having greater proportions of fats. A significantly increased metabolic rate was noted for animals fed a high-fat diet, suggesting a basis for the weight differences. Results also showed that the animals fed calorie-restricted high-fat diets exhibited significant ketonemia and protection from pentylenetetrazole (PTZ)-induced seizures. There were no detectable neurotoxic effects for any diet group. For animals of the same age, there was no correlation between beta-hydroxybutyrate (beta-OHB) and seizure threshold. These findings suggest that beta-OHB is not directly involved in the anticonvulsant mechanism of the diet. Also, data presented here show that the conventional 4:1 ketogenic diet does not confer the greatest level of seizure protection. We conclude that a 6:1 ketogenic diet, which shows no evidence of neurotoxicity, may be maximally efficacious in rats.

Attention Deficit/Hyperactivity Disorder (ADHD) is a childhood psychiatric disorder which when carefully defined, affects around 1% of the childhood population [Swanson JM, Sergeant JA, Taylor E, Sonuga-Barke EJS, Jensen PS, Canwell DP. Attention-deficit hyperactivity disorder and hyperkinetic disorder. Lancet 1998;351:429-433]. The primary symptoms: distractibility, impulsivity and overactivity vary in degree and association in such children, which led DSM IV to propose three subgroups. Only one of these subgroups, the combined subtype: deficits in all three areas, meets the ICD-10 criteria. Since the other two subtypes are used extensively in North America (but not in Europe), widely different results between centres are to be expected and have been reported. Central to the ADHD syndrome is the idea of an attention deficit. In order to investigate attention, it is necessary to define what one means by this term and to operationalize it in such a manner that others can test and replicate findings. We have advocated the use of a cognitive-energetic model [Sanders, AF. Towards a model of stress and performance. Acta Psychologica 1983;53: 61-97]. The cognitive-energetic model of ADHD approaches the ADHD deficiency at three distinct levels. First, a lower set of cognitive processes: encoding, central processing and response organisation is postulated. Study of these processes has indicated that there are no deficits of processing at encoding or central processing but are present in motor organisation [Sergeant JA, van der Meere JJ. Convergence of approaches in localizing the hyperactivity deficit. In Lahey BB, Kazdin AE, editors. Advancements in clinical child psychology, vol. 13. New York: Plenum press, 1990. p. 207-45; Sergeant, JA, van der Meere JJ. Additive factor methodology applied to psychopathology with special reference to hyperactivity. Acta Psychologica 1990;74:277-295]. A second level of the cognitive-energetic model consists of the energetic pools: arousal, activation and effort. At this level, the primary deficits of ADHD are associated with the activation pool and (to some extent) effort. The third level of the model contains a management or executive function system. Barkley [Barkley RA, Behavioral inhibition, sustained attention, and executive functions: constructing a unifying theory of ADHD. Psychological Bulletin 1997;121:65-94] reviewed the literature and concluded that executive function deficiencies were primarily due to a failure of inhibition. Oosterlaan, Logan and Sergeant [Oosterlaan J, Logan GD, Sergeant JA. Response inhibition in ADHD, CD, comorbid ADHD + CD, anxious and normal children: a meta-analysis of studies with the stop task. Journal of Child Psychology and Psychiatry 1998;39:411-426] demonstrated that this explanation was not specific to ADHD but also applied to children with the associated disorders of oppositional defiant and conduct disorder. Other executive functions seem to be intact, while others, are deficient. It is argued here that the cognitive-energetic model is a useful guide for determining not only ADHD deficiencies and associated disorders but also linking human cognitive neuroscience studies with neurobiological models of ADHD using animals [Sadile AG. Multiple evidence of a segmental defect in the anterior forebrain of an animal model of hyperactivity and attention deficits. Neuroscience and Biobehavioral Reviews, in press; Sagvolden T, Sergeant JA. Attention-deficit hyperactivity disorder: from brain dysyfunctions to behaviour. Behavioural Brain Research 1998;94:1-10]. A plea for an integrated attack on this research problem is made and the suggestion that conceptual refinement between levels of analysis is essential for further fundamental work to succeed is offered here.

Just as the molecular and chemistry oriented sciences were adopted as the 20th century medical paradigm, incorporation of the patient's perspective into a relationship-centered medical paradigm has been suggested as appropriate for the 21st century. It is the medical dialogue that provides the fundamental vehicle through which the paradigmatic battle of perspectives is waged and the therapeutic relationship is defined.In many regards, the primary challenge to the field is the development of operationally defined and measurable indicators of medical communication that will provide a valid representation of the conceptual models of the therapeutic relationship. The purpose of this essay is to explore the implications of a relationship-centered medical paradigm on the nature of the patient-physician relationship and its expression in the communication of routine medical practice.An organizing framework for distinguishing commonly measured communication elements into conceptually distinct components is suggested. Application of this framework is illustrated through an empirical study of communication in primary care practice. The results of the study demonstrate the usefulness of this approach in linking communication to models of therapeutic relationships.The importance of medical communication is further explored in a summary of studies that establish its association to outcomes and in an overview of future challenges to the field. Copyright (C) 2000 Elsevier Science Ireland Ltd.

The author outlines his concept of reflective function or mentalization, which is defined as the capacity to think about mental states in oneself and in others. He presents evidence to suggest that the capacity for reflective awareness in a child's caregiver increases the likelihood of the child's secure attachment, which in turn facilitates the development of mentalization in the child. He proposes that a secure attachment relationship offers the child a chance to explore the mind of the caregiver, and in this way to learn about minds; he formulates this model of the birth of the psychological self as a variation on the Cartesian cogito: "My caregiver thinks of me as thinking and therefore I exist as a thinker." This model is then applied to provide insight into some personality-disordered individuals who were victims of childhood abuse. The author proposes (1) that individuals who experience early trauma may defensively inhibit their capacity to mentalize to avoid having to think about their caregiver's wish to harm them; and (2) that some characteristics of severe borderline personality disorder may be rooted in developmental pathology associated with this inhibition. He offers evidence for and some qualifications of this model, and argues that the therapeutic effect of psychoanalysis depends on its capacity to activate patients' ability to evolve an awareness of mental states and thus find meaning in their own and other people's behavior.

Modern medical care is influenced by two paradigms: 'evidence-based medicine' and 'patient-centered medicine'. In the last decade, both paradigms rapidly gained in popularity and are now both supposed to affect the process of clinical decision making during the daily practice of physicians. However, careful analysis shows that they focus on different aspects of medical care and have, in fact, little in common. Evidence-based medicine is a rather young concept that entered the scientific literature in the early 1990s. It has basically a positivistic, biomedical perspective. Its focus is on offering clinicians the best available evidence about the most adequate treatment for their patients, considering medicine merely as a cognitive-rational enterprise. In this approach the uniqueness of patients, their individual needs and preferences, and their emotional status are easily neglected as relevant factors in decision-making. Patient-centered medicine, although not a new phenomenon, has recently attracted renewed attention. It has basically a humanistic, biopsychosocial perspective, combining ethical values on 'the ideal physician', with psychotherapeutic theories on facilitating patients' disclosure of real worries, and negotiation theories on decision making. It puts a strong focus on patient participation in clinical decision making by taking into account the patients' perspective, and tuning medical care to the patients' needs and preferences. However, in this approach the ideological base is better developed than its evidence base. In modern medicine both paradigms are highly relevant, but yet seem to belong to different worlds. The challenge for the near future is to bring these separate worlds together. The aim of this paper is to give an impulse to this integration. Developments within both paradigms can benefit from interchanging ideas and principles from which eventually medical care will benefit. In this process a key role is foreseen for communication and communication research. Copyright (C) 2000 Elsevier Science Ireland Ltd.

Plasma carnitine levels were measured in two alternative nutrition groups--strict vegetarians (vegans) and lactoovovegetarians (vegetarians consuming limited amounts of animal products such as milk products and eggs). The results were compared to an average sample of probands on mixed nutrition (omnivores). Carnitine levels were correlated with the intake of essential amino acids, methionine and lysine (as substrates of its endogenous synthesis), since the intake of carnitine in food is negligible in the alternative nutrition groups (the highest carnitine content is in meat, lower is in milk products, while fruit, cereals and vegetables contain low or no carnitine at all). An average carnitine level in vegans was significantly reduced with hypocarnitinemia present in 52.9% of probands. Similarly, the intake of methionine and lysine was significantly lower in this group due to the exclusive consumption of plant proteins with reduced content of these amino acids. Carnitine level in lactoovovegetarians was also significantly reduced, but the incidence of values below 30 micromol/l was lower than in vegans representing 17.8% vs. 3.3% in omnivores. Intake of methionine and lysine was also significantly reduced in this group, but still higher compared to vegans (73% of protein intake covered by plant proteins). Significant positive correlation of carnitine levels with methionine and lysine intake in alternative nutrition groups indicates that a significant portion of carnitine requirement is covered by endogenous synthesis. Approximately two thirds of carnitine requirement in omnivores comes from exogenous sources. The results demonstrate the risks of alternative nutrition with respect to the intake of essential amino acids, methionine and lysine, and with respect to the intake and biosynthesis of carnitine.

Obesity is among the most important medical problems in America today. Currently, approximately 1 in 4 children and 1 in 2 adults are overweight, prevalence rates that have increased by 50% since the 1960s. In an attempt to combat this problem, the Federal government and various official medical agencies have advocated decreasing intake of total fat and sugar, while increasing consumption of "complex carbohydrate." Despite a recent reduction in fat consumption to near the recommended 30% of total energy, rates of obesity have continued to rise, suggesting that other dietary factors may play a critical role in body weight regulation. One such factor may be glycemic index. This review examines the physiologic effects of glycemic index and argues for the need for controlled clinical trials of a low glycemic index diet in the treatment of obesity.

Mammographic parenchymal patterns are related to breast cancer risk and are also thought to be affected by diet. We designed a case-control study comprising 200 cases with high-risk (P2 and DY) mammographic parenchymal pattern and 200 controls with low-risk (N1 and P1) patterns in order to investigate the effect of food and nutrient intake on mammographic patterns. Mammograms were evaluated according to the Wolfe classification system. Dietary data were obtained from 7-day food diaries. Mean daily intake of nutrients was computed from standard UK food tables. The adjusted odds ratio (OR) of having a high-risk pattern in women in the highest tertile of total protein and carbohydrate intake was twice that of women in the lowest tertile (OR = 2.00; 95% confidence interval (CI) 1.06-3.77; P = 0.04 and OR = 1.93; 95% CI 1.03-3.59; P = 0.04 respectively). There was no excess risk for fat intake. In addition, there was no association between intake of vitamins and mammographic parenchymal patterns. Total meat intake was strongly and positively associated with high-risk patterns among post-menopausal women (OR = 2.50, 95% CI 1.09-5.69, P = 0.03). Our study suggests that certain macronutrients and foods such as protein, carbohydrate and meat intake influence the risk of breast cancer through their effects on breast tissue morphology, whereas fat and vitamins do not affect mammographic density. It seems that parenchymal pattern acts as an informative biomarker of the effect of some macronutrient and foodstuffs intake on breast cancer risk. (C) 2000 Cancer Research Campaign.

"Explores the history of western society's concern for constipation as a serious threat to health, and discusses the extraordinary variety of preventive and curative measures that have been developed to save people from the presumed toxic effects of intestinal irregularity."--Jacket.

More than one-third of adult Americans are obese. A major portion of the diseases that cause the highest morbidity and mortality, eg, heart disease, cancer, diabetes, stroke, and hypertension, can be attributed to diet. Yet, despite the demand for more nutrition education, few medical schools have an adequate nutrition curriculum. Many medical schools are reducing the number of lecture hours in favor of problem-based tutorial discussions, so an addition of another mandatory lecture course is not likely. The organization of nutrition as a theme throughout the 4-y medical school curriculum can pull together many hours of nutrition information taught during various courses, eg, biochemistry, physiology, pathophysiology, clinical clerkships, and electives. Emphasis should be placed on the identification of available resources (eg, faculty throughout the medical school and affiliated hospitals, textbooks, research, and clinical experiences) and applied to practical clinical situations so that students are able to identify, assess, and appropriately manage the frequent nutritional problems seen in outpatients and inpatients. Strategies and techniques such as curriculum analysis, computer-aided instruction modules, Internet Web sites, case-based tutorial discussions, use of physician nutrition specialists and dietitians, administratively separate nutrition units, observed structured clinical examinations, and faculty development are listed and discussed in this article.

BACKGROUND: Pure vegetarian diets might cause cobalamin deficiency due to lack of dietary intake. It was hypothesized that a population following a vegan diet consuming mostly raw fruits and vegetables, carrot juice, and dehydrated barley grass juice would be able to avoid vitamin B12 deficiency naturally. METHODS: Subjects were recruited at a health ministers' reunion based on adherence to the Hallelujah diet for at least 2 years. Serum cobalamin and urinary methylmalonic acid (MMA) assays were performed. Follow-up with sublingual tablets, nutritional yeast, or probiotic supplements was carried out on subjects with abnormal MMA results. RESULTS: 49 subjects were tested. Most subjects (10th to 90th percentile) had followed this diet 23-49 months. 6 subjects had serum B12 concentrations <147 pmol/l (200 pg/ml). 37 subjects (76%) had serum B12 concentrations <221 pmol/l (300 pg/ml). 23 subjects (47%) had abnormal urinary MMA concentrations above or equal to 4.0 microg/mg creatinine. Sublingual cyanocobalamin and nutritional yeast, but not probiotic supplements, significantly reduced group mean MMA concentrations (tablet p < 0.01; yeast p 0.20). CONCLUSIONS: The urinary MMA assay is effective for identifying early metabolic cobalamin deficiency. People following the Hallelujah diet and other raw-food vegetarian diets should regularly monitor their urinary MMA levels, consume a sublingual cobalamin supplement, or consume cobalamin in their food.