Published Science

BACKGROUND: Conduct disorder and delinquency are significant problems for children and adolescents and their families, with the potential to consume much of the resources of the health, social care and juvenile justice systems. A number of family and parenting interventions have been recommended and are used for these conditions. The aim of this review was to determine if these interventions are effective in the management of conduct disorder and delinquency in children and adolescents, aged 10-17. OBJECTIVES: To determine if family and parenting interventions improve the child/adolescent's behaviour; parenting and parental mental health; family functioning and relations; and have an effect on the long term psychosocial outcomes for the child/adolescent. SEARCH STRATEGY: Randomised controlled trials were identified through searching the Cochrane Controlled Trial Register (CCTR), databases (MEDLINE, EMBASE, PsycINFO, CINAHL, Sociofile, ERIC, Healthstar), reference lists of articles and contact with authors. SELECTION CRITERIA: Randomised controlled trials with a major focus on parenting and/or family functioning were eligible for inclusion in the review. Trials needed to include at least one objective outcome measure (e.g. arrest rates) or have used a measure that had been published in peer review publications and validated for the relevant purpose. Studies were required to have a control group, which could be a no intervention group, a wait list group or a usual intervention group (e.g. probation). Trials in children and adolescents aged 10 to 17 years with conduct disorder and/or delinquency and their families were considered. Conduct disorder was defined by a standardised psychological assessment (for example, using a child behaviour checklist), or a psychiatric diagnosis. Delinquency was defined by a referral from a juvenile justice or another legal system for a child/adolescent who has committed a serious crime e.g assault and/or offended on at least two occasions. DATA COLLECTION AND ANALYSIS: Two reviewers independently reviewed all eligible studies for inclusion, assessed study quality (allocation concealment, blinding, follow up, clinically important outcomes) and extracted data. Heterogeneity was assessed using the Chi squared test of heterogeneity along with visual inspection of the data. A significance level less than 0.1 was interpreted as evidence of statistically significant heterogeneity. For data where heterogeneity was found the reviewers looked for an explanation. If studies with heterogeneous results were thought to be comparable the statistical synthesis of the results was done using a random effects model. This model takes into account within-study sampling error and between-studies variation in the assessment of uncertainty and will give wider confidence intervals to the effect size and hence a more conservative result. Sensitivity analysis was performed to explore the effects of the varying quality of the studies included on the results. MAIN RESULTS: Of the nine hundred and seventy titles initially identified through the search strategy, eight trials met the inclusion criteria. A total of 749 children and their families were randomised to receive a family and parenting intervention or to be in a control group. In seven of these studies the participants were juvenile delinquents and their families and in only one the participants were children/adolescents with conduct disorder who had not yet had contact with the juvenile justice system. At follow up, family and parenting interventions significantly reduced the time spent by juvenile delinquents in institutions (WMD 51.34 days, 95%CI 72.52 to 30.16). There was also a significant reduction in the risk of a juvenile delinquent being re arrested (RR 0.66, 95%CI 0.44 to 0.98) and in their rate of subsequent arrests at 1-3 years (SMD -0.56, 95% CI -1.100 to - 0.03). For both of these outcomes there was substantial heterogeneity in the results suggesting a need for caution in interpretation. At present there is insufficient evidence that family and parenting interventions reduce the risk of being incarcerated (RR=0.50, 95% CI 0.20 to 1.21). No significant difference was found for psychosocial outcomes such as family functioning, and child/adolescent behaviour. REVIEWER'S CONCLUSIONS: The evidence suggests that family and parenting interventions for juvenile delinquents and their families have beneficial effects on reducing time spent in institutions. This has an obvious benefit to the participant and their family and may result in a cost saving for society. These interventions may also reduce rates of subsequent arrest but at present these results need to be interpreted with caution due to the heterogeneity of the results.

BACKGROUND: Fibromyalgia engulfs patients in a downward, reinforcing cycle of unrestorative sleep, chronic pain, fatigue, inactivity, and depression. In this study we tested whether a mostly raw vegetarian diet would significantly improve fibromyalgia symptoms. METHODS: Thirty people participated in a dietary intervention using a mostly raw, pure vegetarian diet. The diet consisted of raw fruits, salads, carrot juice, tubers, grain products, nuts, seeds, and a dehydrated barley grass juice product. Outcomes measured were dietary intake, the fibromyalgia impact questionnaire (FIQ), SF-36 health survey, a quality of life survey (QOLS), and physical performance measurements. RESULTS: Twenty-six subjects returned dietary surveys at 2 months; 20 subjects returned surveys at the beginning, end, and at either 2 or 4 months of intervention; 3 subjects were lost to follow-up. The mean FIQ score (n = 20) was reduced 46% from 51 to 28. Seven of the 8 SF-36 subscales, bodily pain being the exception, showed significant improvement (n = 20, all P for trend < 0.01). The QOLS, scaled from 0 to 7, rose from 3.9 initially to 4.9 at 7 months (n = 20, P for trend 0.000001). Significant improvements (n = 18, P

Ketone bodies can replace glucose as the major source of brain energy when glucose becomes scarce. Although it is generally assumed that the liver supplies extrahepatic tissues with ketone bodies, recent evidence shows that astrocytes are also ketogenic cells. Moreover, the partitioning of fatty acids between ketogenesis and ceramide synthesis de novo might control the survival/death decision of neural cells. These findings support the notion that astrocytes might supply neurons with ketone bodies in situ, and raise the possibility that astrocyte ketogenesis is a cytoprotective pathway.

The nonenzymatic glycation of LDL is a naturally occurring chemical modification of apolipoprotein (apo)-B lysine residues by glucose. Once glycated, LDL is only poorly recognized by lipoprotein receptors including the LDL receptor (LDL-R), the LDL-R-related protein (LRP), and scavenger receptors. Glycated LDL (gLDL) is a preferred target for oxidative modifications. Additionally, its presence initiates different processes that can be considered "proatherogenic." Thus, LDL glycation might contribute to the increased atherosclerotic risk of patients with diabetes and familial hypercholesterolemia. Here we investigate whether lipoprotein lipase (LPL) can mediate the cellular uptake of gLDL. The addition of exogenous LPL to the culture medium of human skin fibroblasts, porcine aortic endothelial cells, and mouse peritoneal macrophages enhanced the binding, uptake, and degradation of gLDL markedly, and the relative effect of LPL on lipoprotein uptake increased with the degree of apoB glycation. The efficient uptake of gLDL by LDL-R-deficient fibroblasts and LRP-deficient Chinese hamster ovary cells in the presence of LPL suggested a mechanism that was independent of the LDL-R and LRP. In macrophages, the uptake of gLDL was also correlated with their ability to produce LPL endogenously. Mouse peritoneal macrophages from genetically modified mice, which lacked LPL, exhibited a 75% reduction of gLDL uptake compared with normal macrophages. The LPL-mediated effect required the association of the enzyme with cell surface glycosaminoglycans but was independent of its enzymatic activity. The uptake of gLDL in different cell types by an LPL-mediated process might have important implications for the cellular response after gLDL exposure as well as the removal of gLDL from the circulation.

As we enter the 21st century, a new era of nutrition in the prevention and treatment of disease emerges. Clinical nutrition involves the integration of diet, genetics, environment, and behavior promoting health and well being throughout life. Expertly edited, Nutrition in the Prevention and Treatment of Disease provides overall perspective and current scientifically supported evidence through in-depth reviews, key citations, discussions, limitations, and interpretations of research findings. This comprehensive reference integrates basic principles and concepts across disciplines and areas of research and practice, while detailing how to apply this knowledge in new creative ways. Nutrition in the Prevention and Treatment of Disease is an essential part of the tool chest for clinical nutritionists, physicians, nurse practitioners, and dieticians in this new era of practice. This book prepares the clinical nutrition investigator or practitioner for a life-long commitment to learning. CONTAINS INFORMATION ON: * Diet assessment methodologies * Strategies for diet modification * Clinical status of herbals, botanicals, and modified food products * Preventing common diseases such as cardiovascular disease, diabetes, osteoporosis, and breast cancer through nutrition * The Importance of genetic factors * Understanding of cultural and socio-economic influences on eating and exercise behaviors and integrating that knowledge with biological or functional markers of disease.

Biological amines react with reducing sugars to form a complex family of rearranged and dehydrated covalent adducts that are often yellow-brown and/or fluorescent and include many cross-linked structures. Food chemists have long studied this process as a source of flavor, color, and texture changes in cooked, processed, and stored foods. During the 1970s and 1980s, it was realized that this process, called the Maillard reaction or advanced glycation, also occurs slowly in vivo. Advanced glycation endproducts (AGEs) that form are implicated, causing the complications of diabetes and aging, primarily via adventitious and crosslinking of proteins. Long-lived proteins such as structural collagen and lens crystallins particularly are implicated as pathogenic targets of AGE processes. AGE formation in vascular wall collagen appears to be an especially deleterious event, causing crosslinking of collagen molecules to each other and to circulating proteins. This leads to plaque formation, basement membrane thickening, and loss of vascular elasticity. The chemistry of these later-stage, glycation-derived crosslinks is still incompletely understood but, based on the hypothesis that AGE formation involves reactive carbonyl groups, the authors introduced the carbonyl reagent aminoguanidine hydrochloride as an inhibitor of AGE formation in vivo in the mid 1980s. Subsequent studies by many researchers have shown the effectiveness of aminoguanidine in slowing or preventing a wide range of complications of diabetes and aging in animals and, recently, in humans. Since, the authors have developed a new class of agents, exemplified by 4,5-dimethyl-3-phenacylthiazolium chloride (DPTC), which can chemically break already-formed AGE protein-protein crosslinks. These agents are based on a new theory of AGE crosslinking that postulates that alpha-dicarbonyl structures are present in AGE protein-protein crosslinks. In studies in aged animals, DPTC has been shown to be capable of reverting indices of vascular compliance to levels seen in younger animals. Human clinical trials are underway.

OBJECTIVES: We sought to determine whether sauna therapy, a thermal vasodilation therapy, improves endothelial function in patients with coronary risk factors such as hypercholesterolemia, hypertension, diabetes mellitus and smoking. BACKGROUND: Exposure to heat is widely used as a traditional therapy in many different cultures. We have recently found that repeated sauna therapy improves endothelial and cardiac function in patients with chronic heart failure. METHODS: Twenty-five men with at least one coronary risk factor (risk group: 38±7 years) and 10 healthy men without coronary risk factors (control group: 35±8 years) were enrolled. Patients in the risk group were treated with a 60°C far infrared-ray dry sauna bath for 15 min and then kept in a bed covered with blankets for 30 min once a day for two weeks. To assess endothelial function, brachial artery diameter was measured at rest, during reactive hyperemia (flow-mediated endothelium-dependent dilation [%FMD]), again at rest and after sublingual nitroglycerin administration (endothelium-independent vasodilation [%NTG]) using high-resolution ultrasound. RESULTS: The %FMD was significantly impaired in the risk group compared with the control group (4.0±1.7% vs. 8.2±2.7%, p\textless0.0001), while %NTG was similar (18.7±4.2% vs. 20.4±5.1%). Two weeks of sauna therapy significantly improved %FMD in the risk group (4.0±1.7% to 5.8±1.3%, p\textless0.001). In contrast, %NTG did not change after two weeks of sauna therapy (18.7±4.2% to 18.1±4.1%). CONCLUSIONS: Repeated sauna treatment improves impaired vascular endothelial function in the setting of coronary risk factors, suggesting a therapeutic role for sauna treatment in patients with risk factors for atherosclerosis. © 2001 by the American College of Cardiology.

The world's advanced countries have easy access to plentiful high-fat food; ironically, it is this rich diet that produces atherosclerosis. In the world's poorer nations, many people subsist on a primarily plant-based diet, which is far healthier, especially in terms of heart disease. To treat coronary heart disease, a century of scientific investigation has produced a device-driven, risk factor-oriented strategy. Nevertheless, many patients treated with this approach experience progressive disability and death. This strategy is a rear-guard defensive one. In contrast, compelling data from nutritional studies, population surveys, and interventional studies support the effectiveness of a plant-based diet and aggressive lipid lowering to arrest, prevent, and selectively reverse heart disease. In essence, this is an offensive strategy. The single biggest step toward adopting this strategy would be to have United States dietary guidelines support a plant-based diet. An expert committee purged of industrial and political influence is required to assure that science is the basis for dietary recommendations. (c)2001 CHF, Inc.

5 pages, 2 tables.

In the United States in the XIXth and early XXth centuries, there was a substantial mortality "penalty" to living in urban places. This circumstance was shared with other nations. By around 1940, this penalty had been largely eliminated, and it was healthier, in many cases, to reside in the city than in the countryside. Despite the lack of systematic national data before 1933, it is possible to describe the phenomenon of the urban mortality transition. Early in the XIXth century, the United States was not particularly urban (only 6.1% in 1800), a circumstance which led to a relatively favorable mortality situation. A national crude death rate of 20-25 per thousand per year would have been likely. Some early data indicate that mortality was substantially higher in cities, was higher in larger relative to smaller cities, and was higher in the South relative to the North. By 1900, the nation had become about 40% urban (and 56% by 1940). It appears that death rates, especially in urban areas, actually rose (or at least did not decline) over the middle of the XIXth century. Increased urbanization, as well as developments in transport and commercialization and increased movements of people into and throughout the nation, contributed to this. Rapid urban growth and an inadequate scientific understanding of disease processes contributed to the mortality crisis of the early and middle nineteenth century in American cities. The sustained mortality transition only began about the 1870s. Thereafter the decline of urban mortality proceeded faster than in rural places, assisted by significant public works improvements and advances in public health and eventually medical science. Much of the process had been completed by the 1940s. The urban penalty had been largely eliminated and mortality continued to decline despite the continued growth in the urban share of the population. Si l'on considère le niveau de la mortalité, vivre dans les villes constituait un handicap dans les États-Unis du XIXe et du début du XXe siècle, tout comme dans d'autres pays. Vers 1940, non seulement cette surmortalité a disparu mais, dans de nombreux cas, il est devenu plus sain de vivre dans les villes qu'à la campagne. En dépit de l'absence de données systématiques avant 1933, il est possible de décrire le phénomène de la transition de la mortalité urbaine. Au début du XIXe siècle, la population des États-Unis n'était pas particulièrement urbaine (6,1% en 1800), ce qui conduisait à une situation relativement favorable de la mortalité : probablement 20-25 pour mille de taux brut de mortalité. Les données les plus anciennes indiquent néanmoins que la mortalité était plus élevée dans les villes, plus forte dans les grandes que dans les petites villes, et dans le Sud que dans le Nord. Vers 1900, la population est à 40 % urbaine et cette proportion grimpe à 56 % en 1940. Les taux de mortalité, en particulier dans les zones urbaines, s'élèvent, ou tout au moins stagnent, à partir du milieu du XIXe siècle. La progression de l'urbanisation, le développement des transports et du commerce, les plus fortes migrations internes mais aussi internationales ont contribué à ce phénomène. La croissance urbaine rapide et une méconnaissance des processus morbides contribuèrent à laisser libre cours aux crises de mortalité des villes américaines jusque vers le milieu du XIXe siècle. La transition de la mortalité se met seulement en place dans les années 1870. Désormais, la baisse de la mortalité urbaine est plus rapide que celle des campagnes, soutenue par les progrès des travaux publics, des avancées de la santé publique et peut-être de la médecine. La majeure partie du processus est achevée dans les années 1940. Le handicap urbain a été largement éliminé et la mortalité continue à baisser en dépit de la poursuite de la croissance de la part de population urbaine.

Although the adverse effects of excess adiposity on health outcomes are widely recognized, there is no consensus regarding the most appropriate dietary strategies for managing obesity in youth. Recently, a novel dietary variable termed glycemic load has been postulated to influence hunger and body weight regulation. Glycemic load, a measure of the effects of a meal on blood glucose levels, is determined by the type and the amount of carbohydrate consumed. According to a hypothetical model, ingestion of high-glycemic load meals induces a sequence of hormonal changes that alter partitioning of metabolic fuels, exacerbate hunger, and over the long-term, promote weight gain. This chapter provides an overview of the available evidence suggesting that dietary glycemic load, and its related factor, the glycemic index, should be taken into consideration in the design of weight loss interventions.

In 1996 for the first time a study of state of health, living conditions and nutrition status of 84 persons from the Siberian settlement of the rigorous vegetarians--vegans and 26 aboriginal inhabitants who feed on a traditional mixed diet was carried out. The clinical and laboratory investigations are kept. The positive influencing vegan ration on a serum lipids, body weight, state of cardiovascular system was showed. The contents of vitamin B12 and serum iron in vegans was in normal physiological range. The level of blood calcium was reduced in comparison with control. Increased contents of copper and zinc in blood was marked both in vegans and in control group. The repeated examination of 77 vegans of the same settlement in 1999 has revealed positive alterations in serum lipids: augmentation of cholesterol of high density lipoproteins on the average on 54.3%, that result in a reliable decrease of atherogenicity coefficient. The decrease to normal amounts of blood copper and zinc, and also increase of blood calcium on the average on 16% was marked. However level of calcium remained below than physiological values.

OBJECTIVE: To compare relative weight, weight loss efforts and nutrient intakes among similarly health-conscious vegetarian, past vegetarian and nonvegetarian premenopausal women. METHODS: Demographic data, lifestyle practices and weight loss efforts (by questionnaire), body mass index (BMI;kg/m2) and dietary intake (via multiple-pass 24-hour diet recall) were compared in a convenience sample of 90 current vegetarians, 35 past vegetarians and 68 nonvegetarians. RESULTS: Age (31.9 +/- 8.8), educational attainment, smoking status, alcohol use, physical activity and perceived health status were similar among the three groups of women. BMI did not differ by dietary pattern and averaged 23.7 +/- 4.7 for all women combined. Participants had intentionally lost > or = 10 pounds a mean of 2.1 times, and 39% of women perceived themselves to be overweight; again, no differences were observed among dietary groups. Dietary intakes of vegetarians and current nonvegetarians were consistent with current recommendations for macronutrient composition (< 30% fat,

Rheumatoid arthritis (RA) is characterized by inflammation of the synovial tissues in the joints. A number of papers related to dietary components that are associated with this inflammation are reviewed. In addition, the ecological approach is used to study the links between diet and RA. Multi-country data for prevalence of RA for females from eight and fifteen countries were compared statistically with components of national dietary supply. Fat from meat and offal for the period 2 years before the prevalence data was found to have the highest statistical association with the prevalence of RA (r(2) 0.877, P

The thyroid hormones are very hydrophobic and those that exhibit biological activity are 3',5',3,5-L-tetraiodothyronine (T4), 3',5,3-L-triiodothyronine (T3), 3',5',3-L-triiodothyronine (rT3) and 3,5',-L-diiothyronine (3,5-T2). At physiological pH, dissociation of the phenolic -OH group of these iodothyronines is an important determinant of their physical chemistry that impacts on their biological effects. When non-ionized these iodothyronines are strongly amphipathic. It is proposed that iodothyronines are normal constituents of biological membranes in vertebrates. In plasma of adult vertebrates, unbound T4 and T3 are regulated in the picomolar range whilst protein-bound T4 and T3 are maintained in the nanomolar range. The function of thyroid-hormone-binding plasma proteins is to ensure an even distrubtion throughout the body. Various iodothyronines are produced by three types of membrane-bound cellular deiodinase enzyme systems in vertebrates. The distribution of deiodinases varies between tissues and each has a distinct developmental profile. Thyroid hormones. (1) the nuclear receptor mode is especially important in the thyroid hormone axis that controls plasma and cellular levels of these hormones. (2) These hormones are strongly associated with membranes in tissues and normally rigidify these membranes. (3) They also affect the acyl composition of membrane bilayers and it is suggested that this is due to the cells responding to thyroid-hormone-induced membrane rigidificataion. Both their immediate effects on the physical state of membranes and the consequent changes in membrane composition result in several other thyroid hormone effects. Effects on metabolism may be due primarily to membrane acyl changes. There are other actions of thyroid hormones involving membrane receptors and influences on cellular interactions with the extracellulara matrix. The effects of thyroid hormones are reviewed and appear to b combinations of these various modes of action. During development, vertebrates show a surge in T4 and other thyroid hormones, as well as distinctive profiles in the appearance of the deiodinase enzymes and nuclear receptors. Evidence from the use of analogues supports multiple modes of action. Re-examination of data from th early 1960s supports a membrane action. Findings from receptor 'knockout' mice supports an important role for receptors in the development of the thyroid axis. These iodothyronines may be better thought of as 'vitamone'-like molecules than traditional hormonal messengers.

Biosensor-based immunochemical screening assays for the detection of sulfadiazine (SDZ) and sulfamethazine (SMT) in muscle extract from pigs were developed. Samples were extracted with aqueous buffer and then centrifuged. This simple and straightforward preparation allowed up to 40 samples to be processed and analysed in 1 d. The limits of detection for the assays were found to be 5.6 ng g-1 for SDZ and 7.4 ng g-1 for SMT. These figures were well below the European and US legal limits for sulfonamides (100 ng g-1). The precision (RSD) between runs was

The performance of clinic-referred children aged 6-11 (N = 100) was examined using the Conners' Continuous Performance Test (CPT) and measures of auditory attention (Auditory Continuous Performance Test; ACPT), phonological awareness, visual processing speed, and visual-motor competence. The Conners' CPT overall index was unrelated to measures of visual processing speed or visual-motor competence. Although the Conners' CPT converged with the ACPT, the latter demonstrated age and order effects. Significant variance in Conners' CPT parameters was predicted by phonological awareness measures, suggesting that Reading Disordered (RD) children could be "false positives" on the Conners' CPT. The Conners' CPT overall index, phonological awareness, and visual-motor measures were submitted to a 2 x 2 MANCOVA (ADHD vs. RD, covarying for age and socioeconomic status): a main effect for RD status was found. Children with ADHD did not have higher Conners' CPT scores than did clinical controls; however, children with Reading Disorders did. Phonological measures distinguished RD children from ADHD children and other clinical controls. ADHD children who failed the Conners' CPT were rated by teachers as more hyperactive. Despite the strengths of the Conners' CPT, its utility for differential diagnosis of ADHD is questioned.

2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is the most abundant heterocyclic amine formed in meat and fish during cooking and can be used as a model compound for this class of chemicals possibly involved in human carcinogenesis. Knowing the exposure to heterocyclic amines is important for establishing their role in human diseases. Serum albumin (SA) and globin (Gb) adducts were first tested as biomarkers of exposure to PhIP in male Fischer 344 rats given oral doses of 0.1, 0.5, 1 and 10 mg/kg. Blood samples were collected 24 hr after treatment and PhIP released from SA and Gb after acidic hydrolysis was analyzed by gas chromatography-mass spectrometry or liquid chromatography-tandem mass spectrometry. PhIP-SA and Gb adducts increased linearly with the dose. Studies on 35 volunteers with different dietary habits exhibited that diet was a major determinant in the formation of both adducts. PhIP-SA adducts were significantly higher in meat consumers than in vegetarians (6.7 +/- 1.6 and 0.7 +/- 0.3 fmol/mg SA; respectively, mean +/- SE; p = 0.04, Mann-Whitney U test). The Gb adduct pattern was quantitatively lower but paralleled SA (3 +/- 0.8 in meat consumers and 0.3 +/- 0.1 in vegetarians). PhIP-SA adducts were no different in smokers and in non-smokers. The results show for the first time that PhIP-blood protein adducts are present in humans not given the synthetic compound. Both biomarkers appear to be suitable for assessing dietary exposure and internal PhIP dose and may be promising tools for studying the role of heterocyclic amines in the etiology of colon cancer and other diseases. Copyright 2000 Wiley-Liss, Inc.

Drug therapy with statins and other agents can result in dramatic lipidlowering effects. Despite the wealth of data supporting the beneficial effects of pharmacologic therapy on cardiovascular risk, patients often express a desire to accomplish similar goals with diet alone. And, except for patients with extreme cholesterol elevations, consensus panels all promote dietary therapy as an initial step in the treatment of hyperlipidemia. This review examines a variety of dietary strategies designed to lower lipid levels, including the American Heart Association diet, the Ornish diet, the Mediterranean diet, exercise, phytosterols, fiber, soy products, and fish oil. Though the declines in low-density lipoprotein cholesterol levels with these methods range from 0% to 37%, cardiovascular risk may be more significantly impacted than would be predicted from these changes alone. Significant benefits can be reaped from nonpharmacologic measures.

High levels of small, dense LDL in plasma are associated with increased risk for cardiovascular disease. There are some biochemical characteristics that may render small, dense LDL particles more atherogenic than larger, buoyant LDL particles. First, small, dense LDL particles contain less phospholipids and unesterified cholesterol in their surface monolayer than do large, buoyant LDL particles. This difference in lipid content appears to induce changes in the conformation of apolipoprotein B-100, leading to more exposure of proteoglycan-binding regions. This may be one reason for the high-affinity binding of small, dense LDL to arterial proteoglycans. Reduction of the phospholipid content in the surface monolayer LDL by treatment with secretory phospholipase A2 (sPLA2) forms small, dense LDL with an enhanced tendency to interact with proteoglycans. Circulating levels of sPLA2-IIA appears to be an independent risk factor for coronary artery disease and a predictor of cardiovascular events. In addition, in-vivo studies support the hypothesis that sPLA2 proteins contribute to atherogenesis and its clinical consequences. These data suggest that modification of LDL by sPLA2 in the arterial tissue or in plasma may be a mechanism for the generation of atherogenic lipoprotein particles in vivo, with a high tendency to be entrapped in the arterial extracellular matrix.

For over 25 years eggs have been the icon for the fat, cholesterol and caloric excesses in the American diet, and the message to limit eggs to lower heart disease risk has been widely circulated. The "dietary cholesterol equals blood cholesterol" view is a standard of dietary recommendations, yet few consider whether the evidence justifies such restrictions. Over 50 years of cholesterol-feeding studies show that dietary cholesterol does have a small effect on plasma cholesterol concentrations. The 167 cholesterol feeding studies in over 3,500 subjects in the literature indicate that a 100 mg change in dietary cholesterol changes plasma total cholesterol by 2.2 mg/dL. Today we recognize that dietary effects on plasma cholesterol must be viewed from effects on the atherogenic LDL cholesterol as well as anti-atherogenic HDL cholesterol since the ratio of LDL:HDL cholesterol is a major determinant of heart disease risk. Cholesterol feeding studies demonstrate that dietary cholesterol increases both LDL and HDL cholesterol with little change in the LDL:HDL ratio. Addition of 100 mg cholesterol per day to the diet increases total cholesterol with a 1.9 mg/dL increase in LDL cholesterol and a 0.4 mg/dL increase in HDL cholesterol. On average, the LDL:HDL ratio change per 100 mg/day change in dietary cholesterol is from 2.60 to 2.61, which would be predicted to have little effect on heart disease risk. These data help explain the epidemiological studies showing that dietary cholesterol is not related to coronary heart disease incidence or mortality across or within populations.

For over 25 years eggs have been the icon for the fat, cholesterol and caloric excesses in the American diet, and the message to limit eggs to lower heart disease risk has been widely circulated. The "dietary cholesterol equals blood cholesterol" view is a standard of dietary recommendations, yet few consider whether the evidence justifies such restrictions. Over 50 years of cholesterol-feeding studies show that dietary cholesterol does have a small effect on plasma cholesterol concentrations. The 167 cholesterol feeding studies in over 3,500 subjects in the literature indicate that a 100 mg change in dietary cholesterol changes plasma total cholesterol by 2.2 mg/dL. Today we recognize that dietary effects on plasma cholesterol must be viewed from effects on the atherogenic LDL cholesterol as well as anti-atherogenic HDL cholesterol since the ratio of LDL:HDL cholesterol is a major determinant of heart disease risk. Cholesterol feeding studies demonstrate that dietary cholesterol increases both LDL and HDL cholesterol with little change in the LDL:HDL ratio. Addition of 100 mg cholesterol per day to the diet increases total cholesterol with a 1.9 mg/dL increase in LDL cholesterol and a 0.4 mg/dL increase in HDL cholesterol. On average, the LDL:HDL ratio change per 100 mg/day change in dietary cholesterol is from 2.60 to 2.61, which would be predicted to have little effect on heart disease risk. These data help explain the epidemiological studies showing that dietary cholesterol is not related to coronary heart disease incidence or mortality across or within populations.

BACKGROUND: There is lack of agreement on which dietary regimen is most suitable for treatment of hypertriglyceridemia, especially if high triglyceride concentrations are not due to obesity or alcohol abuse. We compared the effects on blood lipids of a diet high in total and unsaturated fat with a low-fat diet in patients with triglyceride concentrations of > 2.3 mmol/l. METHODS: Nineteen non-obese male outpatients with triglycerides ranging from 2.30 to 9.94 mmol/l received two consecutive diets for 3 weeks each: first a modified high-fat diet (39% total fat, 8% SFA, 15% monounsaturated fatty acids, 1.6% marine n-3 polyunsaturated fatty acids), and then a low-fat diet (total fat 28%, carbohydrates 54%). RESULTS: The high-fat diet significantly decreased triglycerides (-63%), total cholesterol (-22%), VLDL cholesterol (-54%), LDL cholesterol ( 16%), total apoC-III (-27%), apoC-III in apoB containing lipoproteins (apoC-III LpB; -31%) and in HDL (apoC-III nonLpB; -29%), apoE in serum (-33%) and apoB-containing lipoproteins (nonHDL-E; -42%), LpA-I (-16%), insulin (-36%), and leptin (-26%) and significantly increased the means of HDL cholesterol (+8%), LDL size (+6%), lipoprotein lipase (LPL, +11%), hepatic lipase (+13%), and lecithin: cholesterol acyltransferase (LCAT, +2%). The subsequent low-fat diet increased triglycerides (+63%), VLDL cholesterol (+19%), apoC-III (+23%), apoC-III LpB (+44%) apoC-III nonLpB (+17%), apoE (+29%) and nonHDL-E (+43%), and decreased HDL cholesterol (-12%), LPL (-3%), and LCAT (-3%). Changes in triglycerides correlated with changes in LPL activity and insulin levels. CONCLUSIONS: In hypertriglyceridemic patients, a modified diet rich in mono- and n-3 polyunsaturated fatty acids is more effective than a carbohydrate-rich low-fat diet in correcting the atherogenic lipoprotein phenotype.

BACKGROUND: Hip fracture, a major health problem in elderly persons, varies in incidence among the populations of different countries and is directly related to animal protein intake, a finding that suggests that bone integrity is compromised by endogenous acid production consequent to the metabolism of animal proteins. If that is so, vegetable foods might provide a countervailing effect, because they are a rich source of base (bicarbonate) in the form of metabolizable organic anions, which can neutralize protein-derived acid and supply substrate (carbonate) for bone formation. METHODS: We analyzed reported hip fracture incidence (HFI) data among countries (N = 33) in women aged 50 years and older, in relation to corresponding country-specific data on per capita consumption of vegetable and animal foods as reported by the United Nations Food and Agriculture Organization. RESULTS: HFI varied directly with total (r = +.67, p < .001) and animal (r = +.82, p < .001) protein intake and inversely with vegetable protein intake (r = .37, p 1.0. By contrast, among the countries in the highest tertile of HFI, animal protein intake exceeded vegetable protein intake in nearly every case (10 of 11 countries). Among all countries, HFI correlated inversely and exponentially with the ratio of vegetable/animal protein intake (r = -.84, p

CONTEXT: Conventional dietary approaches for the treatment of obesity have generally yielded disappointing results. OBJECTIVE: To examine the effects of a low-glycemic index (GI) diet compared with a standard reduced-fat diet in the management of pediatric obesity. DESIGN: Retrospective cohort study of children attending an outpatient pediatric obesity program from September 1997 to December 1998. SETTING: Academic medical center. PARTICIPANTS: One hundred seven obese but otherwise healthy children. MAIN OUTCOME MEASURES: Changes in body mass index (BMI [calculated as weight in kilograms divided by the square of height in meters]) and body weight from first to last clinic visit. RESULTS: A total of 64 patients received the low glycemic index diet and 43 received the reduced-fat diet for 4.3 vs 4.2 months' mean duration of follow-up, with 3.3 vs 3.3 mean number of visits, respectively. Body mass index (-1.53 kg/m(2) [95% confidence interval, -1.94 to -1.12] vs -0.06 kg/m(2) [-0.56 to + 0. 44], P<.001) and body weight (-2.03 kg [95% confidence interval -3. 19 to -0.88] vs +1.31 kg [ -0.11 to + 2.72], P<.001) decreased more in the low-GI group compared with the reduced-fat group. In multivariate models, these differences remained significant (P

Thyroid storm is a rare disorder characterized by hypertension, hyperthermia, and multiple systems involvement. Early recognition and treatment of thyroid storm are essential in reducing morbidity and mortality from this disorder. We present the case of a patient with an atypical (normothermic, normotensive) presentation of thyroid storm, accompanied by multiple organ dysfunction syndrome, including lactic acidosis and liver dysfunction, both of which are very rare complications. This case highlights both the multiple organ systems that can be involved in thyroid storm and the importance of recognizing atypical presentations of thyroid storm.

OBJECTIVE: The effects of GH therapy on thyroid function among previous reports have shown remarkable discrepancies, probably due to differences in hormone assay methods, degree of purification of former pituitary-derived GH preparations, dosage schedules, diagnostic criteria, patient selection, duration of treatment and study design. These considerations motivated us to investigate whether and how GH replacement therapy changes serum thyroid hormone levels, including the much less studied rT3 levels, in a group of unequivocally GH-deficient children receiving long-term recombinant human GH therapy. PATIENTS AND DESIGN: Twenty clinically and biochemically euthyroid children were studied in two therapeutic conditions: on GH replacement therapy for at least 6 months and without GH replacement, either before GH was started or after GH was withdrawn for 30-60 days. Eight patients were on thyroxine replacement treatment and thyroxine doses were kept constant during the study. Blood was collected before and after 15, 20 and 60 minutes of TRH administration in both therapeutic conditions (with GH and without GH). MEASUREMENTS: Concentrations of thyroid hormone levels were determined only in sera obtained before TRH administration. FT4, T3 and TSH were measured by immunoflourimetric assays and rT2 was measured by immunoradioassay. RESULTS: Patients were classified into two groups, according to basal TSH levels: group I (TSH > 0.4 mU/l, n = 12) and group II (on thyroxine and TSH < 0.05 mU/l, n = 8). In both groups, serum FT4 levels decreased (17. 0 +/- 1.1 vs. 14.3 +/- 0.9 mU/l, P < 0.001, and 18.0 +/- 1.7 vs. 14. 2 +/- 1.7 mU/l, P < 0.01, respectively), serum T3 levels increased (1.8 +/- 0.1 vs. 2.4 +/- 0.2 nmol/l, P < 0.001, and 1.9 +/- 0.3 vs. 2.4 +/- 0.2 nmol/l, P < 0.05, respectively), and serum rT3 levels decreased (0.35 +/- 0.03 vs. 0.25 +/- 0.03 nmol/l, P < 0.01, and 0. 48 +/- 0.06 vs. 0.34 +/- 0.06 nmol/l, P

Ten pairs of normal men were overfed by 5 MJ/d for 21 d with either a carbohydrate-rich or a fat-rich diet (C- and F-group). The two subjects in each pair were requested to follow each other throughout the day to ensure similar physical activity and were otherwise allowed to maintain normal daily life. The increase in body weight, fat free mass and fat mass showed great variation, the mean increases being 1.5 kg, 0.6 kg and 0.9 kg respectively. No significant differences between the C- and F-group were observed. Heat production during sleep did not change during overfeeding. The RQ during sleep was 0.86 and 0.78 in the C- and F-group respectively. The accumulated faecal loss of energy, DM, carbohydrate and protein was significantly higher in the C- compared with the F-group (30, 44, 69 and 51% higher respectively), whereas the fat loss was the same in the two groups. N balance was not different between the C- and F-group and was positive. Fractional contribution from hepatic de novo lipogenesis, as measured by mass isotopomer distribution analysis after administration of [1-(13)C]acetate, was 0.20 and 0.03 in the C-group and the F-group respectively. Absolute hepatic de novo lipogenesis in the C-group was on average 211 g per 21 d. Whole-body de novo lipogenesis, as obtained by the difference between fat mass increase and dietary fat available for storage, was positive in six of the ten subjects in the C-group (mean 332 (SEM 191)g per 21 d). The change in plasma leptin concentration was positively correlated with the change in fat mass. Thus, fat storage during overfeeding of isoenergetic amounts of diets rich in carbohydrate or in fat was not significantly different, and carbohydrates seemed to be converted to fat by both hepatic and extrahepatic lipogenesis.

The high-fat American diet is responsible for an epidemic of coronary artery disease. A plant-based diet with less than 10% fat will prevent coronary disease from developing, halt the progress of existing disease, and even reverse the disease in many patients. Given proper support and education, motivated patients with a history of coronary disease can follow this diet and prevent future cardiac events.

OBJECTIVE: Stool diluting effects of relatively inert material, such as unfermentable dietary fiber, has been proposed as an effect of fiber beneficial to the colon. Stool dilution by increasing bacterial mass may be beneficial or deleterious, depending on bacterial metabolic products. The purpose of this study was to determine the basis for stool weight when two stepwise increases of fiber from all classes of fiber-containing foods were consumed. METHODS: Stool from five men consuming three constant diets containing 15, 30 and 42 g/d of dietary fiber were fractionated into plant material and bacteria and analyzed for neutral and amino sugar content. Fecal nitrogen, fat and ash were measured. RESULTS: Daily gravimetric yield and sugar content of the plant fraction from stool increased with each fiber addition. Compared to the low fiber diet, the medium fiber diet decreased the concentration of the bacterial mass in wet stool by 11% and the high fiber diet by an additional 32%. The high fiber diet decreased stool fat concentration; the medium and high fiber diets decreased stool nitrogen concentration to the same extent. Apparent digestibility of plant-derived neutral sugars decreased with each fiber addition. CONCLUSIONS: Inherently less fermentable plant material modulates the colon environment in three beneficial ways: it is a relatively unreactive diluent of lumenal contents; it adds mass to promote distal movement of waste; it does not promote a large bacterial mass.

Brain tryptophan is low in fibromyalgia. Intake of protein rich in large neutral amino acids is reported to lower brain tryptophan. This study was undertaken to assess whether any reduction of such proteins by exclusion of animal protein from the diet reduced pain and morbidity in fibromyalgia patients. It was an open, randomized controlled trial. 37 subjects with fibromyalgia were enrolled in the vegetarian diet and 41 in the amitriptyline groups. The outcome was assessed with the help of frequencies of fatigue, insomnia & non-restorative sleep, pain score on a 10-point VAS and tender point count. Fatigue, insomnia and non-restorative sleep were present in 41, 26 and 32 subjects before and in 3, 0 and 0 subjects respectively at six weeks of treatment in the amitriptyline group. The pain score and tender point count were 6.2 +/- 1.9 & 16.1 +/- 2.3 before and 2.3 +/- 1.3 & 6.4 +/- 3.0 after treatment. All these differences were significant (P

We report on a 50-year-old man who presented with benign, symmetric lipomatosis and chronic alcoholic liver disease. The characteristic clinical features and a brief review of the current literature are presented. © 2000 Elsevier Science B.V.

Mean serum insulin-like growth factor-I was 9% lower in 233 vegan men than in 226 meat-eaters and 237 vegetarians (P = 0.002). Vegans had higher testosterone levels than vegetarians and meat-eaters, but this was offset by higher sex hormone binding globulin, and there were no differences between diet groups in free testosterone, androstanediol glucuronide or luteinizing hormone. © 2000 Cancer Research Campaign

Mean serum insulin-like growth factor-I was 9% lower in 233 vegan men than in 226 meat-eaters and 237 vegetarians (P = 0.002). Vegans had higher testosterone levels than vegetarians and meat-eaters, but this was offset by higher sex hormone binding globulin, and there were no differences between diet groups in free testosterone, androstanediol glucuronide or luteinizing hormone.

Mean serum insulin-like growth factor-I was 9% lower in 233 vegan men than in 226 meat-eaters and 237 vegetarians (P = 0.002). Vegans had higher testosterone levels than vegetarians and meat-eaters, but this was offset by higher sex hormone binding globulin, and there were no differences between diet groups in free testosterone, androstanediol glucuronide or luteinizing hormone.