Published Science

The aim of this study was to conduct an ecological analysis of the extent to which ultraviolet radiation (UVR) levels might explain the regional variation of multiple sclerosis (MS) in Australia. MS prevalence data for six Australian regions were compared with UVR levels of the largest city in each region, with some other climatic variables and with the melanoma incidence in the same regions. A close association was found between the theoretical MS prevalence predicted from UVR levels and the actual prevalence. Furthermore, the negative correlation between UVR and MS prevalence (r = -0.91, p = 0.01) was higher than the positive correlation observed for UVR and malignant melanoma incidence (r = 0.75, p = 0.15 for males and r = 0.80, p = 0.10 for females). This study demonstrated that the regional variation in MS prevalence in the continent of Australia could be closely predicted by regional UVR levels. It is consistent with the hypothesis that UVR exposure may reduce the risk of MS possibly via T-lymphocyte-mediated immunosuppression. Analytical epidemiology studies are required to investigate this specific hypothesis.

Induced apoptosis of autoreactive T-lymphocyte precursors in the thymus is crucial for the prevention of autoimmune disorders. IGF-I and prolactin, which are lymphocyte growth factors, may have the potential to suppress apoptosis in thymocytes and thus encourage autoimmunity; conversely, dietary fish oil rich in omega-3 fats appears to upregulate apoptosis in lymphocytes. Since whole-food vegan diets may downregulate systemic IGF-I activity, it is proposed that such a diet, in conjunction with fish oil supplementation and treatment with dopamine agonists capable of suppressing prolactin secretion, may have utility for treating and preventing autoimmune disorders. This prediction is consistent with the extreme rarity of autoimmune disorders among sub-Saharan black Africans as long as they followed their traditional quasi-vegan lifestyles, and with recent ecologic studies correlating risks for IDDM and for multiple sclerosis mortality with animal product and/or saturated fat consumption. Moreover, there is evidence that vegan or quasi-vegan diets are useful in the management of rheumatoid arthritis, multiple sclerosis, and possibly SLE. The dopamine agonist bromocryptine exerts anti-inflammatory effects in rodent models of autoimmunity, and there is preliminary evidence that this drug may be clinically useful in several human autoimmune diseases; better tolerated D2-specific agonists such as cabergoline may prove to be more practical for use in therapy. The moderate clinical utility of supplemental fish oil in rheumatoid arthritis and certain other autoimmune disorders is documented. It is not unlikely that extra-thymic anti-inflammatory effects contribute importantly to the clinical utility of vegan diets, bromocryptine, and fish oil in autoimmunity. The favorable impact of low latitude or high altitude on autoimmune risk may be mediated by superior vitamin D status, which is associated with decreased secretion of parathyroid hormone; there are theoretical grounds for suspecting that parathyroid hormone may inhibit apoptosis in thymocytes. Androgens appear to up-regulate thymocyte apoptosis, may be largely responsible for the relative protection from autoimmunity enjoyed by men, and merit further evaluation for the management of autoimmunity in women. It will probably prove more practical to prevent autoimmune disorders than to reverse them once established; a whole-food vegan diet, coupled with fish oil and vitamin D supplementation, may represent a practical strategy for achieving this prevention, while concurrently lowering risk for many other life-threatening 'Western' diseases.

Method: Hospitalized patients with schizophrenia received one to three injections of intramuscular olanzapine, 10 mg, intramuscular haloperidol, 7.5 mg, or intramuscular placebo over a 24-hour period. Agitation was measured with the excited component of the Positive and Negative Syndrome Scale and two additional scales. Results: According to scores on the excited component of the Positive and Negative Syndrome Scale, both intramuscular olanzapine and intramuscular haloperidol reduced agitation significantly more than intramuscular placebo 2 and 24 hours following the first injection. Intramuscular olanzapine reduced agitation significantly more than intramuscular haloperidol 15, 30, and 45 minutes following the first injection. No patients treated with intramuscular olanzapine experienced acute dystonia, compared with 7% of those who were treated with intramuscular haloperidol. No significant QTc interval changes were observed in any patients. Conclusions: Intramuscular olanzapine represents a rapid, effective, and safe treatment for acute agitation in schizophrenia.

OBJECTIVE: To evaluate the effectiveness, tolerability, and adverse effects of the ketogenic diet in infants with refractory epilepsy. METHODS: A retrospective review of 32 infants who had been treated with the ketogenic diet at a large metropolitan institution. RESULTS: Most infants (71%) were able to maintain strong ketosis. The overall effectiveness of the diet in infants was similar to that reported in the literature for older children; 19.4% became seizure-free, and an additional 35.5% had >50% reduction in seizure frequency. The diet was particularly effective for patients with infantile spasms/myoclonic seizures. There were concomitant reductions in antiepileptic medications. The majority of parents reported improvements in seizure frequency and in their child's behavior and function, particularly with respect to attention/alertness, activity level, and socialization. The diet generally was well-tolerated, and 96.4% maintained appropriate growth parameters. Adverse events, all reversible and occurring in one patient each, included renal stone, gastritis, ulcerative colitis, alteration of mentation, and hyperlipidemia. CONCLUSION: The ketogenic diet should be considered safe and effective treatment for infants with intractable seizures.

Thiamine requirements for humans are generally expressed as absolute values per day (mg/d) or in relation to total caloric intake. Limited data are available on the relation between thiamine requirements and the intake of carbohydrates. This study was performed to investigate the influence of stepwise increases of carbohydrate intake on the status of thiamine in healthy volunteers under isocaloric conditions. During an adaptation phase of four days, the carbohydrate intake of twelve healthy volunteers (6 male, 6 female) was 55% of total energy intake. During the subsequent intervention periods, carbohydrate intake was increased to 65% of total energy for four days and to 75% for another four days. Thiamine intake, total energy intake, and physical activity were kept constant throughout the study. HPLC analysis was used to measure thiamine in plasma, urine and feces. Erythrocyte transketolase activity (ETK) was determined enzymatically. During the intervention periods thiamine decreased significantly (p

This paper describes the clinical manifestations of attention-deficit/hyperactivity disorder (ADHD) in adulthood, with particular emphasis placed on issues relating to comorbidity. Prospective and retrospective studies are reviewed to evaluate the degree to which adults with ADHD exhibit clinical features that mirror their childhood counterparts with analogous comorbid psychiatric (e.g., antisocial, mood, and anxiety) and/or cognitive (i.e., learning) disorders. We also address the question of whether comorbid disorders in adults represent independent diagnostic entities and whether the presence of psychiatric comorbidity varies as a function of ADHD subtype (i.e., inattentive, hyperactive-impulsive, combined, and residual). As is the case for ADHD in childhood, comorbidity is not uncommon among adults with ADHD. However, the reported prevalence of comorbid conditions among adults with ADHD varies considerably depending upon whether the research used a prospective or retrospective design.

This article reviews research on the growth and nutrient intake of vegan children and provides guidelines for counselling parents of vegan children. Although diets of vegan children meet or exceed recommendations for most nutrients, and vegan children have higher intakes of fiber and lower intakes of total fat, saturated fat, and cholesterol than omnivore children, some studies indicate that they may be low in calcium. In addition, bioavailability of zinc and iron from plant foods can be low. Protein needs are slightly higher for vegan children but are easily met with a varied diet that provides adequate energy. Special attention should be given to dietary practices that enhance absorption of zinc and iron from plant foods. Further, good sources of the omega-3 fatty acid linolenic acid should be emphasized to enhance synthesis of the long-chain fatty acid docosahexanoic acid. Dietetics professionals who counsel vegan families should help parents identify good sources of vitamin B-12, riboflavin, zinc, calcium and, if sun exposure is not adequate, vitamin D. This should not be problematic, due to the growing number and availability of fortified vegan foods that can help children meet all nutrient needs. Therefore, with appropriate food choices, vegan diets can be adequate for children at all ages.

Appropriately planned vegan diets can satisfy nutrient needs of infants. The American Dietetic Association and The American Academy of Pediatrics state that vegan diets can promote normal infant growth. It is important for parents to provide appropriate foods for vegan infants, using guidelines like those in this article. Key considerations when working with vegan families include composition of breast milk from vegan women, appropriate breast milk substitutes, supplements, type and amount of dietary fat, and solid food introduction. Growth of vegan infants appears adequate with post-weaning growth related to dietary adequacy. Breast milk composition is similar to that of non-vegetarians except for fat composition. For the first 4 to 6 months, breast milk should be the sole food with soy-based infant formula as an alternative. Commercial soymilk should not be the primary beverage until after age 1 year. Breastfed vegan infants may need supplements of vitamin B-12 if maternal diet is inadequate; older infants may need zinc supplements and reliable sources of iron and vitamins D and B-12. Timing of solid food introduction is similar to that recommended for non-vegetarians. Tofu, dried beans, and meat analogs are introduced as protein sources around 7-8 months. Vegan diets can be planned to be nutritionally adequate and support growth for infants.

OBJECTIVE: The study investigated the nutritional status of Chinese lacto-ovo-vegetarian children aged 4-14 years. METHODOLOGY: Dietary intake over 7 days was assessed using a computer program, previously used for a local population-based dietary survey. Anthropometric measurements were made and fasting venous blood was examined for serum lipids, haematological data, iron, vitamin B12 and folate status. Bone mineral density (BMD) of the spine (L2 - L4) was measured as a reflection of calcium status. RESULTS: Fifty-one lacto-ovo-vegetarians aged 4-14 years were investigated. The mean +/- standard deviation (SD) daily energy intake was 1600 +/- 425 kcal. The mean (+/- SD) daily protein intake was 1.6 +/- 0.6 g/kg bodyweight which met the United States recommended dietary allowance. Compared to that of the local omnivore diet, the vegetarian diet was closer to the recommended healthy diet with lower fat (20-23%), more fibre (5.8-8.7 g/day) and better polyunsaturated to saturated fatty acid ratio (1.0-1.1). Growth and BMD of the vegetarian children were comparable to the general omnivore population. Two children had iron deficiency and two children had anaemia. The calcium status, as reflected by the BMD, was not impaired. Serum folate and vitamin B12 were within the normal range. Six (25%) boys and four (15%) girls were obese. Three boys had hyperlipidaemia. CONCLUSIONS: A Hong Kong Chinese vegetarian diet appears healthy, providing adequate iron and vitamin B12 nutrition, but the prevalence of obesity was high.

We examined the effects of a high-fat diet (HFD-CHO) versus a habitual diet, prior to carbohydrate (CHO)-loading on fuel metabolism and cycling time-trial (TT) performance. Five endurance-trained cyclists participated in two 14-day randomized cross-over trials during which subjects consumed either a HFD (> 65% MJ from fat) or their habitual diet (CTL) (30 +/- 5% MJ from fat) for 10 day, before ingesting a high-CHO diet (CHO-loading, CHO > 70% MJ) for 3 days. Trials consisted of a 150-min cycle at 70% of peak oxygen uptake (VáO2peak), followed immediately by a 20-km TT. One hour before each trial, cyclists ingested 400 ml of a 3.44% medium-chain triacylglycerol (MCT) solution, and during the trial, ingested 600 ml/hour of a 10% 14C-glucose + 3.44% MCT solution. The dietary treatments did not alter the subjects' weight, body fat, or lipid profile. There were also no changes in circulating glucose, lactate, free fatty acid (FFA), and b-hydroxybutyrate concentrations during exercise. However, mean serum glycerol concentrations were significantly higher (p < .01) in the HFD-CHO trial. The HFD-CHO diet increased total fat oxidation and reduced total CHO oxidation but did not alter plasma glucose oxidation during exercise. By contrast, the estimated rates of muscle glycogen and lactate oxidation were lower after the HFD-CHO diet. The HFD-CHO treatment was also associated with improved TT times (29.5 +/- 2.9 min vs. 30.9 +/- 3.4 min for HFD-CHO and CTL-CHO, p

The medical and neurological conditions that simulate ADHD are reviewed, as well as those disorders frequently presenting as comorbidities with ADHD. The localization of ADHD has invoked multiple areas, including frontal lobes, nondominant parietal lobe, and basal ganglia, and the neural network theory of cortical-subcortical-cortical loops has been implicated in the pathogenesis of ADHD. The medical evaluation of patients presenting with ADHD should be comprehensive, with an emphasis on demonstrating chronic and permeating symptoms since early childhood without a better medical explanation. Associated thyroid disorders are reviewed, including the syndrome of resistance to thyroid hormone. Suggested laboratory studies are provided, depending on the clinical circumstances.

Effects of different psychological stimuli on oxytocin (OT) and vasopressin (AVP) secretion are reviewed in animals and in humans. The secretion of neuropituitary hormones is also discussed in various psychiatric diseases such an anorexia nervosa, bipolar disorder, schizophrenia and obsessive-compulsive disorder. AVP and OT are secreted into the hypophyseal portal circulation by neurons which project from the paraventricular nucleus to the external zone of the median eminence. AVP and OT-containing neurons in the suprachiasmatic and paraventricular nuclei project to limbic areas, including the hippocampus, the subiculum, the ventral nucleus of the amygdala and the nucleus of the diagonal band. Specific AVP receptors which are pharmacologically different from the pressor and antidiuretic AVP receptors have been found in the anterior pituitary. OT receptors have been identified in a variety of forebrain sites. The neurohypophyseal secretion is regulated by the cholinergic muscarinic, histaminergic and beta-adrenergic systems. Stress alters the secretion of one or more of the hypothalamic factors which interact at the pituitary to increase the secretion of ACTH. AVP and OT have been shown to modulate the effect of Corticotropin-Releasing Factor (CRF) on ACTH secretion and appear to play a key role in mediating the ACTH response to stress. Although AVP is a relatively weak secretagogue for ACTH, it markedly potentiates the activity of CRF both in vitro and in vivo. The role of OT is more complex. In vitro, OT stimulates ACTH release at high doses whereas in human it inhibits ACTH secretion at low doses. The type of stressor appear to determine the relative importance of these secretatogues in ACTH response. Several recent studies indicate that psychological stressors display a similar degree of variety of secretagogue release patterns as was found earlier for physical stressors. A bewildering array of technique produces a bewildering array of conclusions. In rats, OT may be an important secretagogue during a novel stimulus, whereas the role for AVP is less clear. Indeed two studies out of ten suggest a stimulating role for AVP. In response to frustration and submission, OT and AVP are secreted. Regarding social isolation, results are difficult to interpret and the role of AVP could be species-dependent. In contrast plasma OT levels do not change. After restraint, ACTH release is primarily mediated by the active increase of OT and AVP does not appear to play a role. When restraint is associated with moderate levels of physical components and during immobilisation, all two secretagogs are involved in the ACTH response. With fear, ACTH response appears to be driven by OT. In humans, one study indicates that high emotionality women increase plasma OT in response to uncontrollable noise. Various neuroendocrine dysregulations have been observed in psychiatric disease. Either an increase or a decrease of the hypothalamic-pituitary-adrenal (HPA) function have been described in several illnesses. Effects of OT appear to be reciprocal to the effects of AVP. OT has been called the "amnestic" neuropeptide due to its capacity to attenuate memory consolidation and retrieval. AVP exhibits a central activating action on mood, memory and selective attention. Underweight patients with anorexia nervosa have abnormally high levels of centrally directed AVP and reduced OT levels. These modifications could enhance the retention of cognitive distortions of aversive consequences of eating. Patients with bipolar disorder show a biphasic secretion of AVP. Depressive episodes are associated with decreased vasopressinergic activity whereas manic episodes involve an increased release. AVP might be responsible for an increased catecholamine activity. In addition, lithium could act as an antagonist to AVP. In schizophrenic patients, studies using the apomorphine stimulation suggest increased oxytoninergic and decreased vasopressinergic functions. These findings are consistent with the beneficial role of AVP on schizophrenic symptoms noted in several trials. The increased OT could be responsible for "positive" symptomatology such as delusions and hallucinations. Obsessive compulsive disorder (OCD) includes a range of cognitive and behavioral disturbances that could be influenced by OT. In animals, several studies have emphasized the role of AVP in promoting repetitive grooming behaviors and maintaining conditioned response to aversive stimuli. In OCD patients, one study have reported that AVP/OT ratio was negatively correlated with symptom severity. However, an independent report found similar AVP concentrations in OC patients without a personal or family history of tic disorder and in normal subjects. Whether these modifications are only a consequence of the central disturbances or whether those peptides could participate in the pathogenesis of these affections remains to be elucidated.

Background Intestinal gas is thought to be the cause abdominal discomfort in infants. Little is known about the type and amount of gas produced by the infant's colonic microflora and whether diet influences gas formation. Methods Fresh stool specimens were collected from 10 breast-fed infants, 5 infants fed a soy-based formula, and 3 infants fed a milk-based formula at approximately 1, 2, and 3 months of age. Feces were incubated anaerobically for 4 hours at 37°C followed by quantitation of hydrogen (H 2 ), methane (CH 4 ), carbon dioxide (CO 2 ), hydrogen sulfide (H 2 S), methanethiol (CH 3 SH), and dimethyl sulfide (CH 3 SCH 3 ) in the head-space. Results H 2 was produced in greater amounts by breast-fed infants than by infants in either formula group, presumably the consequence of incomplete absorption of breast milk oligosaccharides. CH 4 was produced in greater amounts by infants fed soy formula than by infants on other diets. CO 2 was produced in similar amounts by infants in all feeding groups. Production of CH 3 SH was conspicuously low by feces of breast-fed infants and production of H 2 S was high by soy-formula–fed infants. CH 3 SCH 3 was not detected. Only modest changes with age were observed and there was no relation between gas production and stool consistency, although stools were more likely to be malodorous when concentrations of H 2 S and/or CH 3 SH were high. Conclusions Gas release by infant feces is strongly influenced by an infant's diet. Of particular interest are differences in production of the highly toxic sulfur gases, H 2 S and CH 3 SH, because of the role that these gases may play in certain intestinal disorders of infants.

Questions remain concerning the effect of variations in cholesterol intake on plasma cholesterol concentration, as well as on the role of factors modulating the metabolic impact of this dietary intervention. To define the impact of wide variations in dietary cholesterol intake on plasma total and low-density lipoprotein (LDL) cholesterol concentrations, as well as testing the hypothesis that resistance to insulin-mediated glucose disposal would accentuate the increase in plasma total and LDL cholesterol concentrations in response to a given increment in dietary cholesterol intake, we performed a prospective, randomized study comparing diets varying in cholesterol content in 65 healthy, postmenopausal women, 31 defined as insulin-resistant and 34 as insulin-sensitive. The changes in total and LDL cholesterol in response to increments in dietary cholesterol of up to approximately 800 mg/day were modest in magnitude, without evidence of a statistically significant diet-induced increase in cholesterol concentration, or of any difference in the responses of insulin-resistant as compared with insulin-sensitive women. These results indicate that relatively large increments in dietary cholesterol intake had little effect on total or LDL cholesterol concentrations in healthy, postmenopausal women, irrespective of whether they were insulin-resistant or insulin-sensitive.

PURPOSE: Little is known about the factors that influence housestaff attitudes toward pharmaceutical industry promotions or, how such attitudes correlate with physician behaviors. We studied these attitudes and practices among internal medicine housestaff. SUBJECTS AND METHODS: Confidential surveys about attitudes and behaviors toward industry gifts were distributed to 1st- and 2nd-year residents at a university-based internal medicine residency program. RESULTS: Ninety percent of the residents (105 of 117) completed the survey. A majority of respondents considered seven of nine types of promotions appropriate. Residents judged the appropriateness of promotions on the basis of their cost (median percentage of items considered appropriate 100% for inexpensive items vs. 60% for expensive ones) more than on the basis of their educational value (80% for educational items vs.75% for noneducational ones; P < .001 for comparison of appropriateness based on cost vs. educational value). Behaviors were often inconsistent with attitudes; every resident who considered conference lunches (n = 13) and pens (n = 18) inappropriate had accepted these gifts. Most respondents (61%)stated that industry promotions and contacts did not influence their own prescribing, but only 16% believed other physicians were similarly unaffected (P

Ketosis, meaning elevation of D-beta-hydroxybutyrate (R-3hydroxybutyrate) and acetoacetate, has been central to starving man's survival by providing nonglucose substrate to his evolutionarily hypertrophied brain, sparing muscle from destruction for glucose synthesis. Surprisingly, D-beta-hydroxybutyrate (abbreviated "betaOHB") may also provide a more efficient source of energy for brain per unit oxygen, supported by the same phenomenon noted in the isolated working perfused rat heart and in sperm. It has also been shown to decrease cell death in two human neuronal cultures, one a model of Alzheimer's and the other of Parkinson's disease. These observations raise the possibility that a number of neurologic disorders, genetic and acquired, might benefit by ketosis. Other beneficial effects from betaOHB include an increased energy of ATP hydrolysis (deltaG') and its linked ionic gradients. This may be significant in drug-resistant epilepsy and in injury and anoxic states. The ability of betaOHB to oxidize co-enzyme Q and reduce NADP+ may also be important in decreasing free radical damage. Clinical maneuvers for increasing blood levels of betaOHB to 2-5 mmol may require synthetic esters or polymers of betaOHB taken orally, probably 100 to 150 g or more daily. This necessitates advances in food-science technology to provide at least enough orally acceptable synthetic material for animal and possibly subsequent clinical testing. The other major need is to bring the technology for the analysis of multiple metabolic "phenotypes" up to the level of sophistication of the instrumentation used, for example, in gene science or in structural biology. This technical strategy will be critical to the characterization of polygenic disorders by enhancing the knowledge gained from gene analysis and from the subsequent steps and modifications of the protein products themselves.

Gallic acid (GA), a food component that is especially abundant in tea, is an antimutagenic, anticarcinogenic and anti-inflammatory agent. We conducted a study using acidum gallicum tablets that contained 10% GA and 90% glucose and a black tea brew that contained 93% of its GA in free form to determine the pharmacokinetics and relative bioavailability of GA in healthy humans. After the administration of a single oral dose of acidum gallicum tablets or tea (each containing 0.3 mmol GA) to 10 volunteers, plasma and urine samples were collected over various time intervals. Concentrations of GA and its metabolite, 4-O-methylgallic acid (4OMGA), were determined, and the pharmacokinetic parameters were calculated. GA from both the tablets and tea was rapidly absorbed and eliminated with mean half-lives of 1.19 +/- 0.07 and 1.06 +/- 0.06 h and mean maximum concentrations of 1.83 +/- 0.16 and 2.09 +/- 0.22 micromol/L (plasma), respectively. After oral administration of the tablets and black tea, 36.4 +/- 4.5 and 39.6 +/- 5.1% of the GA dose were extracted in urine as GA and 4OMGA, respectively. The relative bioavailability of GA from tea compared with that from the tablets was 1.06 +/- 0.26, showing that GA is as available from drinking tea as it is from swallowing tablets of GA.

It is widely appreciated that health food beverages are not appropriate for infants. Because of continued growth, children beyond infancy remain susceptible to nutritional disorders. We report on 2 cases of severe nutritional deficiency caused by consumption of health food beverages. In both cases, the parents were well-educated, appeared conscientious, and their children received regular medical care. Diagnoses were delayed by a low index of suspicion. In addition, nutritional deficiencies are uncommon in the United States and as a result, US physicians may be unfamiliar with their clinical features. Case 1, a 22-month-old male child, was admitted with severe kwashiorkor. He was breastfed until 13 months of age. Because of a history of chronic eczema and perceived milk intolerance, he was started on a rice beverage after weaning. On average, he consumed 1.5 L of this drink daily. Intake of solid foods was very poor. As this rice beverage, which was fallaciously referred to as rice milk, is extremely low in protein content, the resulting daily protein intake of 0.3 g/kg/day was only 25% of the recommended dietary allowance. In contrast, caloric intake was 72% of the recommended energy intake, so the dietary protein to energy ratio was very low. A photograph of the patient after admission illustrates the typical features of kwashiorkor: generalized edema, hyperpigmented and hypopigmented skin lesions, abdominal distention, irritability, and thin, sparse hair. Because of fluid retention, the weight was on the 10th percentile and he had a rotund sugar baby appearance. Laboratory evaluation was remarkable for a serum albumin of 1.0 g/dL (10 g/L), urea nitrogen <0.5 mg/dL (

A complete diet was prepared with cooked pieces of meat, beans, cream starch, and water and presented to the rats in two different textures: a blended purée and a rough mixture that required a lot of chewing. We hypothesized that this texture modification might change both anticipatory reflexes and feeding behavior. Feeding rate, meal size, intermeal intervals, and their correlation were monitored in response to each texture. The long-term (6 wk) effect on body weight was assessed. Periprandial plasma glucose, insulin, glucagon, and lipid concentrations were assayed. Whole and background metabolism, respiratory quotient, and locomotion were measured using a computerized calorimeter of original design. In the short term, rats preferred the mixture. However, after 3 wk, they ingested more purée than mixture and gained more body weight per gram of food ingested as purée. Insulin response declined earlier with the mixture. During meals, glycerol and free fatty acid increased earlier with purée, whereas in the postprandial period, glycerol increased earlier with mixture. The metabolic rate, however, was not significantly affected. We concluded that texture, an everyday manipulation performed on food for human consumption, affects not only palatability of ingestants but also their metabolic management in the short and long term.

The explanatory utility of a theory or model of ADHD or any disorder depends fundamentally on its capacity to address issues of causality. What causes a particular child to develop ADHD? What mechanisms are responsible for temporal and setting-related variations in symptom severity, and how are these mechanisms affected by pharmacological intervention? And, what processes determine whether gains in one domain will propagate across one or more others? It should be evident from the foregoing discussion that comprehensive answers to such questions are most likely to emerge through implementation of research strategies that (a) integrate biological and psychological levels of explanation, (b) permit analysis of causal hypotheses, and (c) address mechanisms involved in both etiology and mediation of treatment response. Although extant neurobiological studies of ADHD are as compelling as they are exciting, they are limited by a troubling reductionistic emphasis. The predominant animal models focus on a narrow range of behaviors that are presumed to be central to ADHD because of the topographic similarity they bear to those represented by the diagnostic criteria incorporated into the diagnostic nomenclature. These models would become increasingly valuable to the extent that future research examined the extent to which ecologically relevant behaviors (e.g., social behavior) are compromised in the animal strains and whether the observed compromises are parallel to the correlates of ADHD observed in humans. Similarly, human molecular genetic studies have provided a glimpse into the possible role that genes related to dopaminergic neurotransmission may play in the etiology of ADHD. Yet, the features of ADHD have been conceptualized in these investigations as a unitary collection of characteristics, and this has precluded analysis of what specific syndromal feature (if any single one) is affected by the implicated genes. It is intriguing to speculate whether varying combinations of genes governing properties of DA receptors and reuptake molecules are associated with different patterns of symptom severity or responses to stimulant medications. As testing procedures for determining genotypes with respect to these features become more affordable and available, it should become increasingly feasible to examine such issues empirically. Research on the utility of stimulant drugs as a treatment for ADHD also has yielded useful information. Although the effects of MPH are of short duration, the breadth of their impact is impressive. The clinical effectiveness of these medications is no longer in doubt, and patterns of relations among outcome measures represent a potentially fruitful target of scientific inquiry. Finally, data supporting a neurobiological substrate for ADHD, evidence indicating that task and setting variables moderate the expression of the syndrome's diagnostic features (see Barkley, 1998, for a review), and the causal emphasis of the conceptual model with which the discussion began collectively argue for a diathesis-stress conception of the syndrome. And, as foregoing comments make clear, task and setting variables and the mechanisms through which they influence symptom expression are as important to the phenomenon as are neurobiological predisposing causes. This has significant implications for assessment strategies employed in diagnosis and evaluation of treatment-outcome. Specifically, it suggests that theory-based experimental manipulations of task and setting variables designed to impose challenge on hypothesized core features of the disorder are more likely to yield insights into the causal mechanisms governing behavioral organization in affected children than strategies emphasizing static identification of diagnostic correlates. It is hoped that such an approach will accelerate the discovery of increasingly effective assessment and intervention strategies.

OBJECTIVE: To evaluate whether subclinical hypothyroidism (SH) affects resting energy expenditure (REE) as well as body composition, lipid profile, and serum leptin in obese patients. RESEARCH METHODS AND PROCEDURES: A total of 108 obese patients with SH defined as normal free thyroxine levels and thyroid-stimulating hormone (TSH) values of > 4.38 microU/ml (mean +/- 2 SD of the values of our reference group of obese patients with normal thyroid function) were compared with a group of 131 obese patients matched for age, sex, and body mass index (BMI) but with normal TSH levels. We assessed estimated daily caloric intake by 7-day recall, REE by indirect calorimetry, body composition by bioelectrical impedance analysis, serum leptin by radioimmunoassay, and lipid profile (i.e., total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides). RESULTS: All of the variables measured were not different between the euthyroid obese patients and those with SH. In a multiple regression model with REE expressed for kilograms of fat free mass (REE/kgFFM) as a dependent variable and percentage of fat mass, BMI, waist-to-hip ratio, age, TSH, free thyroxine, serum leptin, and caloric intake as independent variables, only percentage of fat mass was significantly correlated with REE/kgFFM in both groups. In the SH group only, BMI, waist-to-hip ratio, age, and TSH were related to REE/kgFFM and explained 69.5% of its variability. After dividing the patients with SH using a cutoff TSH value of 5.7 microU/ml, which represents 3 SD above the mean of TSH levels of the group of obese patients with normal thyroid function, only REE/kgFFM was significantly different and lower in the group of more severely hypothyroid patients. DISCUSSION: In patients with obesity, SH affects energy expenditure only when TSH is clearly above the normal range; it does not change body composition and lipid profile. We suggest that, at least in obese patients, evaluation of TSH levels may be useful to rule out a possible impairment of resting energy expenditure due to a reduced peripheral effect of thyroid hormones.

The effects of a strict uncooked vegan diet on serum lipid and sterol concentrations were studied in patients with rheumatoid arthritis. The subjects were randomized into a vegan diet group (n 16), who consumed a vegan diet for 2-3 months, or into a control group (n 13), who continued their usual omnivorous diets. Serum total and LDL-cholesterol and -phospholipid concentrations were significantly decreased by the vegan diet. The levels of serum cholestanol and lathosterol also decreased, but serum cholestanol:total cholesterol and lathosterol:total cholesterol did not change. The effect of a vegan diet on serum plant sterols was divergent as the concentration of campesterol decreased while that of sitosterol increased. This effect resulted in a significantly greater sitosterol:campesterol value in the vegan diet group than in the control group (1.48 (SD 0.39) v. 0.72 (SD 0.14); P

Iodine deficiency (ID) and related disorders are still major, yet unresolved health concerns. Recently, in a systematic survey of school-age children (SAC), we reported severe to moderate ID, in Ankara and three cities from Black Sea region of Turkey. The current study attempted to evaluate selenium (Se) status, thiocyanate (SCN-) overload, and their possible contribution to the goiter endemics and thyroid hormone profile observed in these cities. Thyroid ultrasonography was performed and serum Se, SCN(-), thyroid hormones, sensitive TSH (sTSH) levels, and, urinary iodine concentrations (UICs) were determined from 251 SAC (9-11 yr old). Thyroid volumes (TVs) exceeding recommended upper normal limits and median UIC indicated goitre endemics and moderate to severe ID in the areas studied. Mean serum SCN(-) concentrations were found to be greater than the controls from the literature. The UIC/SCN(-) ratio was found to be lowest in Bayburt and Trabzon denoting that SCN(-) overload may contribute to the goiter endemics. Serum Se concentrations represent a marginal deficiency in the four areas studied. No significant correlations between serum Se concentrations and the other parameters studied (i.e., TV, SCN(-), thyroid hormones, sTSH, UIC) was detected. In conclusion, this study showed that selenium is also marginally deficient in the iodine-deficient endemic areas studied, but this has little or no impact on the thyroid hormone profile and the goiter endemics. SCN(-) overload may contribute to the endemics, especially for the areas where iodine is severely deficient. An effective iodine supplementation program will not only resolve the goiter endemics but also the consequence of SCN(-) overload as well in the endemic goiter areas studied.

Ghrelin, an endogenous ligand for growth hormone secretagogue (GHS) receptor originally isolated from the stomach, occurs in the hypothalamic arcuate nucleus and may play a role in energy homeostasis. Synthetic GHSs have activated the hypothalamic arcuate neurons containing neuropeptide Y (NPY), suggesting the involvement of NPY in some of ghrelin actions. This study was designed to elucidate the role of ghrelin in the regulation of food intake. A single intracerebroventricular (ICV) injection of ghrelin (5-5,000 ng/rat) caused a significant and dose-related increase in cumulative food intake in rats. Ghrelin (500 ng/rat) was also effective in growth hormone-deficient spontaneous dwarf rats. Hypothalamic NPY mRNA expression was increased in rats that received a single ICV injection of ghrelin (500 ng/rat) (approximately 160% of that in vehicle-treated groups, P < 0.05). The ghrelin's orexigenic effect was abolished dose-dependently by ICV co-injection of NPY Y1 receptor antagonist (10-30 microg/rat). The leptin-induced inhibition of food intake was reversed by ICV co-injection of ghrelin in a dose-dependent manner (5-500 ng/rat). Leptin reduced hypothalamic NPY mRNA expression by 35% (P

BACKGROUND: Adjustments of carbohydrate intake and oxidation occur in both normal-weight and overweight individuals. Nevertheless, the contribution of carbohydrates to the accumulation of fat through either reduction of fat oxidation or stimulation of fat synthesis in obesity remains poorly investigated. OBJECTIVE: The objective of this study was to assess the postprandial metabolic changes and the fractional hepatic de novo lipogenesis (DNL) induced by a high-carbohydrate, low-fat meal in lean and overweight young men. DESIGN: A high-carbohydrate, low-fat meal was administered to 6 lean and 7 overweight men after a 17.5-h fast. During the fasting and postprandial periods, energy expenditure (EE), macronutrient oxidation, diet-induced thermogenesis, and serum insulin, glucose, triacylglycerol, and fatty acids were measured. To determine DNL, [1-13C]sodium acetate was infused and the mass isotopomer distribution analysis method was applied. RESULTS: After intake of the high-carbohydrate meal, the overweight men had hyperinsulinemia and higher fatty acid and triacylglycerol concentrations than did the lean men. The overweight group showed a greater EE, whereas there was no significant difference in carbohydrate oxidation between the groups. Nevertheless, the overweight men had a marginally higher protein oxidation and a lower lipid oxidation than did the lean men. DNL was significantly higher before and after meal intake in the overweight men and was positively associated with fasting serum glucose and insulin concentrations. Furthermore, postprandial DNL was positively correlated with body fat mass, EE, and triacylglycerol. CONCLUSION: After a high-carbohydrate, low-fat meal, overweight men had a lower fat oxidation and a higher fractional hepatic fat synthesis than did lean men.

The association of a particular mitochondrial DNA (mtDNA) mutation with different clinical phenotypes is a well-known feature of mitochondrial diseases. A simple genotype-phenotype correlation has not been found between mutation load and disease expression. Tissue and intercellular mosaicism as well as mtDNA copy number are thought to be responsible for the different clinical phenotypes. As disease expression of mitochondrial tRNA mutations is mostly in postmitotic tissues, studies to elucidate disease mechanisms need to be performed on patient material. Heteroplasmy quantitation and copy number estimation using small patient biopsy samples has not been reported before, mainly due to technical restrictions. In order to resolve this problem, we have developed a robust assay that utilizes Molecular Beacons to accurately quantify heteroplasmy levels and determine mtDNA copy number in small samples carrying the A8344G tRNA(Lys) mutation. It provides the methodological basis to investigate the role of heteroplasmy and mtDNA copy number in determining the clinical phenotypes.

OBJECTIVES: This study addressed whether food and nutrient intakes were correlated with skin wrinkling in a sun-exposed site. METHODS: 177 Greek-born subjects living in Melbourne (GRM), 69 Greek subjects living in rural Greece (GRG), 48 Anglo-Celtic Australian (ACA) elderly living in Melbourne and 159 Swedish subjects living in Sweden (SWE) participating in the International Union of Nutritional Sciences IUNS "Food Habits in Later Life" study had their dietary intakes measured and their skin assessed. Food and nutrient intakes were assessed using a validated semi-quantitative food frequency questionnaire (FFQ). Skin wrinkling was measured using a cutaneous microtopographic method. RESULTS: SWE elderly had the least skin wrinkling in a sun-exposed site, followed by GRM, GRG and ACA. Correlation analyses on the pooled data and using the major food groups suggested that there may be less actinic skin damage with a higher intake of vegetables (r(s)=-0.31, p<0.0001), olive oil (r(s)=-0.29, p<0.0001), fish (r(s)=-0.24, p<0.0001) and legumes (r(s)=-0.16, p<0.0001), and lower intakes of butter (r(s)=0.46, p<0.0001) and margarine (r(s)=0.24, p<0.001), milk products (r(s)=0.16, p<0.01) and sugar products (r(s)=0.12, p<0.01). Similar findings were obtained using regression analyses, except fish was no longer significant; 32% of the variance for actinic skin damage was predicted by six out of the ten major food groups. In particular, a high intake of vegetables, legumes and olive oil appeared to be protective against cutaneous actinic damage (collectively explaining 20% of the variance); a high intake of meat, dairy and butter appeared to be adverse (explaining

Geological and archeological research indicates that humans "rst colonized the Americas with the use of watercraft along the southern coast of the Bering Land Bridge and the western coast of the Americas. Early dates from a number of archeological sites in the Americas indicate human colonization of the Americas began prior to ca. 13,000 BP. A review of archeological sites in eastern Beringia identi"es several distinctive cultural traditions which had developed by 11,000}10,000 BP. Geological, biological, linguistic evidence, and dated human skeletal remains all suggest human occupation of the Americas prior to ca. 11,500 BP. Glacial geology indicates colonization could have begun ca. 14,000}13,000 BP along the western coasts of the Americas and ended about 5000 BP with deglaciation of the Canadian eastern Arctic and coastal Greenland. The use of watercraft and coastal navigation prior to 11,000 BP are inferentially demonstrated. A model for early coastal and subsequent inland colonization of the Americas along large ecological zones best "ts current geologic and archeological data. 2000 Elsevier Science Ltd. All rights reserved.

A vegan diet in the child and adolescent can induce severe bone sequelae by rickets and osteomalacia and megaloblastic anemia by cobalamin deficiency. CASE REPORT: A 15-year-old adolescent was hospitalized because of lameness and pallor. The lameness was explained by femoral epiphysiolysis caused by rickets with severe hypocalcemia. The pallor, jaundice and splenomegalia were due to cobalamin-deficiency megaloblastic anemia. A prolonged supplemental diet with calcium, vitamins D and B12 as well as orthopedic treatment stabilized the bone lesions. The megaloblastic anemia was cured by parenteral cobalamin. The adolescent and his brother were victims of a diet imposed by a cult and a lack of care due to their parents refusing that a vegan diet was the cause of the deficient pathology. Penal proceedings led to the incarceration of the parents and to the placement of the children. COMMENTS: Deficiencies in calcium and vitamins D and B12 may be severe in a child's development with a vegan diet. This case report reveals the social and legal problems of an inappropriate diet in infancy imposed by parents who are followers of a fundamentalist church. Beyond the management of children in cults, health professionals have to prevent, screen and supplement the deficient diet.

In this review many examples are given of the complexities involved in using some biomarkers in relation to assessing the effects of dietary exposure, when there is frequently a need to determine changes following long-term low level exposure to dietary components. These range from understanding why the biomarker might be valuable and how best it can be measured, to the pitfalls which can occur in the interpretation of data. Analytical technique is considered in relation to folate and selenium, and flavonoid and carotenoid species are used to illustrate how the metabolism of a compound may alter the validity or adequacy of a marker. Vitamin A is discussed in relation to the difficulties which can arise when there are several biomarkers that may be available to assess exposure to one nutrient. Vitamin B12 is discussed in relation to the dietary choices made by individuals. Possible interactions and the role of measuring total antioxidant capacity is considered in some detail. In contrast to most nutrients, there is a marked lack of biomarkers of either exposure or effect for most non-nutrients. The role of biological effect monitoring is considered for dietary contaminants, fumonisins and polyhalogenated aromatic hydrocarbons. Aflatoxins are discussed to exemplify food contaminants for which the biomarker approach has been extensively studied. Finally some compounds which are deliberately added to foods and some which appear as processing contaminants are each considered briefly in relation to the requirement for a biomarker of exposure to be developed.

One of the problems which may beset epidemiological studies is the difficulty of accurately measuring the dietary intakes of participants. Biomarkers of diet promise to provide a more accurate measure of dietary intake and a more objective one in that they are not reliant on the subject's memory. This review considers some issues of importance in epidemiology when information is obtained from biomarkers. The approach taken is to use examples both of normal dietary constituents and of contaminants in relation to a range of diet and health questions to illustrate these points. A brief overview of the role of sample collection, processing and storage is given including some generic recommendations for maximising the reliability of subsequent analytical data. Using the examples of phytoestrogens and iodine the question of whether biomarkers can accurately reflect the intake of the dietary constituents of interest at the population level or at the individual level is considered. The relationship of the biomarker to the natural history of the disease is exemplified using the role of folate in neural tube defects. Finally, intakes of vitamin D and heterocyclic amines are used to illustrate the integration of biomarkers into epidemiological studies of prostate and colorectal cancer, respectively. It is concluded that biomarkers may provide a more accurate and objective measure of diet than estimates of current or usual intake but that this approach also has limitations. A combination of methods will probably prove to be most valuable and this approach is being taken in current large prospective studies.

Purpose and Background: To demonstrate the application of Leventhal's Self-Regulation Model with a group of Chinese immigrants with type 2 diabetes. Design and Methods: Using qualitative methods and a convenience sample of 30 Chinese immigrants, interviews were analyzed by categorizing data according to the components of the Leventhal model. Participants were recruited from a U.S. West Coast Chinatown health center and were interviewed to identify beliefs about health and illness that are shaped by cultural factors. Findings: Application of the self-regulation model indicated that participants were unclear about the etiology and chronicity of diabetes and interpreted the illness as stigmatizing. Coping strategies included wishful thinking, belief in powerful others, keeping diabetes a secret, and avoiding social situations. Participants lacked the ability to appraise the effects of their coping strategies. Conclusions: Health care providers can help people with type 2 diabetes develop critical-thinking strategies instead of relying on sets of rules to gain control of blood glucose levels. The self-regulation model was useful in profiling a vulnerable group whose diabetes management, social environment, and self-image could be improved through thoughtful patient education strategies.

Irrelevant sound tends to break through selective attention and impair cognitive performance. This observation has been brought under systematic scrutiny by laboratory studies measuring interference with memory performance during exposure to irrelevant sound. These studies established that the degree of interference depends on the properties of the irrelevant sound as well as those of the cognitive task. The way in which this interference increases or diminishes as characteristics of the sound and of the cognitive task are changed reveals key functional characteristics of auditory distraction. A number of important practical implications that arise from these studies are discussed, including the finding that relatively quiet background sound will have a marked effect on efficiency in performing cognitive tasks.

Excessive bruising is a symptom noted by parents of some children treated with the ketogenic diet for epilepsy control, although this side effect is not reported in the literature. We evaluated our cohort of current and past diet-treated patients for symptoms of bruising or bleeding through chart review and prospective screening at clinic follow-up visits. A significant increase in bruising or other minor bleeding was reported and/or observed in 16 of 51 patients (31.4%). There were no differences in sex distribution or number of anticonvulsants used between patients with bruising/bleeding and those without this symptom, although the group with bruising/bleeding was significantly younger. No specific anticonvulsant was associated with bruising/bleeding. Six patients with diet-induced bruising/bleeding underwent an investigation for bleeding diathesis. Five of these patients had prolonged bleeding times and all had diminished responsiveness to various platelet aggregating agents, with no evidence of a release defect. The abnormalities all normalized in the 1 patient tested after ceasing the diet. No patients had serious hemorrhage. One patient had mild von Willebrand disease, which had been asymptomatic before diet initiation. Some patients were Stimate® responsive, suggesting a treatment for more severe bouts of symptoms. These data suggest that a ketogenic diet–related bleeding tendency occurs in about one third of treated patients owing to preexisting factors defining susceptibility in combination with diet-induced depression of platelet responsiveness, possibly related to changes in platelet membrane lipid composition and/or concentration and resultant effects on function of membrane-embedded proteins. Patients on the diet undergoing anticoagulation or surgery should be evaluated carefully for symptoms of bleeding tendency. Ann Neurol 2001;49:98–103

Summary: The use of the Cre/loxP system has greatly empowered the field of gene targeting. Here we describe the successful establishment of a novel knock-in EGFP reporter mouse line to monitor Cre-induced recombination in the vast majority of cell types. The value of this reporter mouse line is demonstrated by the use of a novel Tie2Cre transgenic mouse line that facilitates gene targeting in endothelial and hematopoietic cells. High efficiency of recombination was found in all endothelial cells and in the majority of hematopoietic cells but was absent in other tissues. Furthermore, in the second generation, the Tie2Cre mouse can be used to get 100% recombination of one allele, whilst allowing tissue specific in the second, therefore offering excellent efficiency. genesis 30:36–44, 2001. © 2001 Wiley-Liss, Inc.

We define animal husbandry as prey conservation. Conservation is rare among extant hunters and only likely to occur when prey are highly valued, private goods. The long-term discounted deferred returns from husbandry must also be greater than the short-term returns from hunting. We compare the returns from hunting and husbanding strategies as a function of prey body size. Returns from husbanding are estimated using a maximum sustainable yield (MSY) model. Following Charnov (1993), allometric analyses show that the MSY is nearly independent of prey body size. The opportunity costs of husbanding are measured as prey standing biomass times the discount rate. Since standing biomass scales positively with body size, the opportunity costs of husbanding are greater for larger animals. An evolutionary discount rate is estimated following Rogers (1994) to be between 2.4% and 6%. Using these values, the prey body size for which hunting and meat-only husbanding provide the same return is approximately 40kg. Animals greater than 40kg are predicted to be hunted, [animal husbandry, evolutionary ecology, allometry, hunting, Neolithic transition]

Various components of garlic and aged garlic extract, including allicin, S-allylcysteine (SAC) and volatile metabolites of allicin were determined in breath, plasma and simulated gastric fluids by HPLC, gas chromatography (GC) or HPLC- and GC-mass spectrometry (MS). Data indicate that allicin decomposes in stomach acid to release allyl sulfides, disulfides and other volatiles that are postulated to be metabolized by glutathione and/or S-adenosylmethionine to form allyl methyl sulfide. SAC can be absorbed by the body and can be determined in plasma by HPLC or HPLC-MS using atmospheric pressure chemical ionization (APCI)-MS.

We have tested whether differences in distribution and dietary responsiveness of low-density lipoprotein (LDL) subclasses contribute to the variability in the magnitude of LDL-cholesterol reduction induced by diets low in total and saturated fat and high in carbohydrate. Our studies have focused on a common, genetically influenced metabolic profile, characterized by a predominance of small, dense LDL particles (subclass pattern B), that is associated with a two- to threefold increase in risk for coronary artery disease. We have found that healthy normolipidemic individuals with this trait show a greater reduction in LDL cholesterol and particle number in response to low-fat, high-carbohydrate diets than do unaffected individuals (subclass pattern A). Moreover, such diets result in reduced LDL particle size, with induction of pattern B in a substantial proportion of pattern A men. Recent studies have indicated that this response is under genetic influence. Future identification of the specific genes involved may lead to improved targeting of dietary therapies aimed at reducing cardiovascular disease risk.