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PURPOSE: To determine whether the fear response is the same in AN as in controls. METHOD: We recorded the EEG in 10 participants with a history of AN and in 10 controls during a fear stimulus. The response of the brain was recorded using EEG LORETA. The recording was analyzed for a marked increase in activity in the amygdala, uncus, insula, and anterior cingulate from 300 to 500 ms following the stimulus. RESULTS: The order or response of the amygdala, uncus, insula, and anterior cingulate was not significantly different in AN and controls. CONCLUSION: These results suggest that the brain's response to a fear stimulus is not significantly different in AN and controls. LEVEL OF EVIDENCE: Level 3, case-control study.

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PURPOSE: Overweight/obesity, sleep disturbance, night eating, and a sedentary lifestyle are common co-occurring problems. There is a tendency for them to co-occur together more often than they occur alone. In some cases, there is clarity as to the time course and evolution of the phenomena. However, specific mechanism(s) that are proposed to explain a single co-occurrence cannot fully explain the more generalized tendency to develop concurrent symptoms and/or disorders after developing one of the phenomena. Nor is there a clinical theory with any utility in explaining the development of co-occurring symptoms, disorders and behaviour and the mechanism(s) by which they occur. Thus, we propose a specific mechanism-dysregulation of core body temperature (CBT) that interferes with sleep onset-to explain the development of the concurrences. METHODS: A detailed review of the literature related to CBT and the phenomena that can alter CBT or are altered by CBT is provided. RESULTS: Overweight/obesity, sleep disturbance and certain behaviour (e.g. late-night eating, sedentarism) were linked to elevated CBT, especially an elevated nocturnal CBT. A number of existing therapies including drugs (e.g. antidepressants), behavioural therapies (e.g. sleep restriction therapy) and bright light therapy can also reduce CBT. CONCLUSIONS: An elevation in nocturnal CBT that interferes with sleep onset can parsimoniously explain the development and perpetuation of common co-occurring symptoms, disorders and behaviour including overweight/obesity, sleep disturbance, late-night eating, and sedentarism. Nonetheless, a significant correlation between CBT and the above symptoms, disorders and behaviour does not necessarily imply causation. Thus, statistical and methodological issues of relevance to this enquiry are discussed including the likely presence of autocorrelation. LEVEL OF EVIDENCE: Level V, narrative review.

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Environmental factors, such as ambient temperature m(AT), may have a causal role in the development of anorexia nervosa (AN), in addition to factors like the idealization of thinness. We present the literature and a bibliographic analysis that associate AN and a temperate climate.

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BACKGROUND: Rest cramps (also known as nocturnal leg cramps) are very common in a geriatric population. Oral magnesium supplements are marketed for prophylaxis of such cramps but clinical trials exploring the efficacy of oral magnesium conflict. A therapeutic trial of intravenous magnesium overcomes the limited oral bioavailability of magnesium and better assesses its therapeutic potential. METHODS: A double blind, placebo controlled randomized controlled trial was conducted on 46 community-dwelling older adult (69.3 ± 7.7 years) rest cramp sufferers to determine whether 5 consecutive days infusion of 20-mmol (5 g) magnesium sulfate would reduce the frequency of leg cramps per week in the 30 days immediately pre and post infusions. It was also determined whether the response to treatment varied with the extent to which infused magnesium was retained (as measured by 24-hour urinary magnesium excretion). RESULTS: The study population averaged 8.0 cramps per week at baseline. The mean change in number of cramps per week, magnesium versus placebo arms, was -2.4 versus -1.7, p = .51, 95% confidence interval of the difference -3.1 to 1.7. Magnesium retention did not correlate with treatment response. CONCLUSIONS: Intravenous magnesium infusion did not reduce the frequency of leg cramps in a group of older adult rest cramp sufferers regardless of the extent to which infused magnesium was retained. Although oral magnesium is widely marketed to older adults for the prophylaxis of leg cramps, our data suggest that magnesium therapy is not indicated for the treatment of rest cramps in a geriatric population.

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BACKGROUND: Overweight and obese persons are at risk of a number of medical conditions which can lead to further morbidity and mortality. The primary objective of this study is to provide an estimate of the incidence of each co-morbidity related to obesity and overweight using a meta-analysis. METHODS: A literature search for the twenty co-morbidities identified in a preliminary search was conducted in Medline and Embase (Jan 2007). Studies meeting the inclusion criteria (prospective cohort studies of sufficient size reporting risk estimate based on the incidence of disease) were extracted. Study-specific unadjusted relative risks (RRs) on the log scale comparing overweight with normal and obese with normal were weighted by the inverse of their corresponding variances to obtain a pooled RR with 95% confidence intervals (CI). RESULTS: A total of 89 relevant studies were identified. The review found evidence for 18 co-morbidities which met the inclusion criteria. The meta-analysis determined statistically significant associations for overweight with the incidence of type II diabetes, all cancers except esophageal (female), pancreatic and prostate cancer, all cardiovascular diseases (except congestive heart failure), asthma, gallbladder disease, osteoarthritis and chronic back pain. We noted the strongest association between overweight defined by body mass index (BMI) and the incidence of type II diabetes in females (RR = 3.92 (95% CI: 3.10-4.97)). Statistically significant associations with obesity were found with the incidence of type II diabetes, all cancers except esophageal and prostate cancer, all cardiovascular diseases, asthma, gallbladder disease, osteoarthritis and chronic back pain. Obesity defined by BMI was also most strongly associated with the incidence of type II diabetes in females (12.41 (9.03-17.06)). CONCLUSION: Both overweight and obesity are associated with the incidence of multiple co-morbidities including type II diabetes, cancer and cardiovascular diseases. Maintenance of a healthy weight could be important in the prevention of the large disease burden in the future. Further studies are needed to explore the biological mechanisms that link overweight and obesity with these co-morbidities.

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BACKGROUND: Anorexia nervosa (AN) and bulimia nervosa (BN) are classified as separate and distinct clinical disorders. Recently, there has been support for a transdiagnostic theory of eating disorders, which would reclassify them as one disorder. OBJECTIVE: To determine whether AN and BN are a single disorder with one cause or separate disorders with different causes. METHOD: Hill's Criteria of Causation were used to test the hypothesis that AN and BN are one disorder with a single cause. Hill's Criteria of Causation demand that the minimal conditions are needed to establish a causal relationship between two items which include all of the following: strength of association, consistency, temporality, biological gradient, plausibility, coherence, experimental evidence and analogy. RESULTS: The hypothesis that AN and BN have a single cause did not meet all of Hill's Criteria of Causation. Strength of association, plausibility, analogy and some experimental evidence were met, but not consistency, specificity, temporality, biological gradient, coherence and most experimental evidence. CONCLUSIONS: The hypothesis that AN and BN are a single disorder with a common cause is not supported by Hill's Criteria of Causation. This argues against the notion of a transdiagnostic theory of eating disorders.

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OBJECTIVE: Severely malnourished patients with anorexia nervosa (AN) are reported to show fewer symptomatic viral infections and a poorer response to bacterial infection than controls. They are also reported to show mild immune system changes, although the relevance of these to altered infection disease presentation in AN and AN pathophysiology is unknown. Thus, in this paper, we suggest a range of immune system changes that might underpin these altered responses to common pathogens, and review a number of recent infectious disease findings for their utility in explaining the pathophysiology of AN. METHODS: A systematic review of the literature pertaining to immunity and infectious disease in AN was performed. RESULTS: AN is associated with leucopenia, and the increased spontaneous and stimulated levels of proinflammatory cytokines [i.e. interleukin (IL)-1ß, IL-6 and tumour necrosis factor α). A range of less consistent findings are also reviewed. Most of these data were not controlled for length of illness, degree of malnutrition, micronutrient or vitamin deficiencies or recent refeeding and starvation. CONCLUSION: Cytokine disturbances have been suggested to be causally related to AN symptomatology and pathophysiology of AN, although the evidence supporting this assertion is lacking. Immune and cytokine changes in AN do, however, occur in association with a decreased incidence of symptomatic viral infection, decreased clinical response to bacterial infection leading to delayed diagnosis and increased morbidity and mortality associated with the infections.

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OBJECTIVE: To compare the prediction of percentage body fat using BMI and visceral adipose tissue (VAT) using waist circumference (WC) in individuals of Chinese, European, and South Asian origin. RESEARCH METHODS AND PROCEDURES: Healthy men and women of Chinese, European, and South Asian origin (n = 627) between the ages of 30 and 65 years were recruited to ensure equal distribution of gender and representation across BMI ranges (18.5 to 24.9, 25 to 29.9, and >or=30 kg/m(2)). Participants were assessed for demographics, anthropometry, lifestyle, and regional adiposity. Percentage body fat and VAT were measured by DXA and computer tomography scan, respectively. RESULTS: BMI and WC were highly correlated with total and regional measures of adiposity in each ethnic group. At any BMI, the percentage body fat of Chinese participants was similar to that of Europeans, but that of South Asians was greater by 3.9% (p < 0.001). Above a WC of 71.0 cm, the Chinese participants had an increasingly greater amount of VAT than the Europeans (p = 0.017 for interaction). South Asians had significantly more VAT than the Europeans at all but the most extreme WC (above 105 cm) (p < 0.05). DISCUSSION: Compared with Europeans, percentage body fat was higher for a given BMI in South Asians, whereas VAT was higher for a given WC in both Chinese and South Asian men and women. These findings support the use of ethnic-specific anthropometric targets.

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BACKGROUND: Despite the high prevalence of obesity and diabetes in the Canadian Aboriginal population, it is unknown whether the current thresholds for body mass index and waist circumference derived from white populations are appropriate for Aboriginal people. We compared the risk of cardiovascular disease among Canadian Aboriginal and European populations using the current thresholds for body mass index and waist circumference. METHODS: Healthy Aboriginal (n = 195) and European (n = 201) participants (matched for sex and body mass index range) were assessed for demographic characteristics, lifestyle factors, total and central adiposity and risk factors for cardiovascular disease. Among Aboriginal and European participants, we compared the relation between body mass index and each of the following 3 factors: percent body fat, central adiposity and cardiovascular disease risk factors. We also compared the relation between waist circumference and the same 3 factors. RESULTS: The use of body mass index underestimated percent body fat by 1.3% among Aboriginal participants compared with European participants (p = 0.025). The use of waist circumference overestimated abdominal adipose tissue by 26.7 cm2 among Aboriginal participants compared with European participants (p = 0.007). However, there was no difference in how waist circumference estimated subcutaneous abdominal and visceral adipose tissue among the 2 groups. At the same body mass index and waist circumference, we observed no differences in the majority of cardiovascular disease risk factors among Aboriginal and European participants. The prevalence of dyslipidemia, hypertension, impaired fasting glucose and metabolic syndrome was similar among participants in the 2 groups after adjustment for body mass index, waist circumference, age and sex. INTERPRETATION: We found no difference in the relation between body mass index and risk of cardiovascular disease between men and women of Aboriginal and European descent. We also found no difference between waist circumference and cardiovascular disease risk among these groups. These data support the use of current anthropometric thresholds in the Canadian Aboriginal population.

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OBJECTIVE: Investigators have reported that weight gain attributed to clozapine is associated with its clinical response. However, weight gain is a nonspecific physiological variable that, in itself, does not explain the mechanism underlying this relation. Alternatively, other biological variables that are often associated with weight gain, such as serum lipids, may assist in explaining this observation. The primary objective of this study was to determine whether an increase in serum lipids is associated with improvement in schizophrenia symptoms during steady state treatment with clozapine. METHODS: The data for this study represent a subset of data from a randomized, double-blinded trial that evaluated subjects with schizophrenia who demonstrated a poor treatment response to clozapine. While continuing their clozapine therapy, subjects were randomly assigned to receive either risperidone 3 mg daily or placebo for 8 weeks. This course of treatment was followed by an optional (open-label) 18 weeks of augmentation with risperidone. In the present study, we included all subjects from the previously reported trial who had fasting lipid analyses and Positive and Negative Syndrome Scale (PANSS) scores from days 7 and 63 (n = 55). For the primary analyses, we used multiple regression to examine the association between serum lipid concentrations and PANSS scores, after controlling for weight. RESULTS: The analyses showed that the change in serum lipid concentration predicted change in symptoms over that of change in weight. Specifically, an increase in serum triglyceride concentration was associated with a decrease in the total PANSS score (p = 0.037). In addition, an increase in either serum total cholesterol concentration (p = 0.007), serum triglyceride concentration (p = 0.017) or their combined effect (p = 0.010) was associated with a decrease in PANSS negative subscale scores. CONCLUSION: Elevation of serum lipids is associated with an improvement in schizophrenia symptoms in subjects treated with clozapine. Although the mechanism is unclear, serum lipids may play a role in influencing clozapine's therapeutic activity.

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BACKGROUND: It was suggested that body fat distribution differs across ethnic groups, and this may be important when considering risk of disease. Previous studies have not adequately investigated differences in discrete regions of abdominal adiposity across ethnic groups. OBJECTIVE: We compared the relation between abdominal adipose tissue and total body fat between persons living in Canada of Aboriginal, Chinese, and South Asian origin with persons of European origin. DESIGN: Healthy Aboriginal, Chinese, European, and South Asian participants (n = 822) aged between 30 and 65 y were matched by sex, ethnicity, and body mass index (BMI; in kg/m(2)) range. Total abdominal adipose tissue (TAT), subcutaneous abdominal adipose tissue (SAT), visceral adipose tissue (VAT), total body fat mass, lifestyle, and demographics were assessed. Relations between BMI and total body fat, TAT, SAT, and VAT and between total body fat and TAT, SAT, and VAT were investigated. RESULTS: BMI significantly underestimated VAT in all non-European groups. Throughout a range of total body fat mass, VAT was not significantly different between the Aboriginals and the Europeans. With total body fat >9.1 kg, Chinese participants had increasingly greater amounts of VAT than did the Europeans (P for interaction = 0.008). South Asians had less VAT with total body fat >37.4 kg but more VAT below that amount than did Europeans (P for interaction < 0.001). CONCLUSION: Compared with Europeans, the Chinese and South Asian cohorts had a relatively greater amount of abdominal adipose tissue, and this difference was more pronounced with VAT. No significant differences were observed between the Aboriginals and the Europeans.

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BACKGROUND AND PURPOSE: The association between abdominal obesity and atherosclerosis is believed to be due to excess visceral adipose tissue (VAT), which is associated with traditional risk factors. We hypothesized that VAT is an independent risk factor for atherosclerosis. METHODS: Healthy men and women (N=794) matched for ethnicity (aboriginal, Chinese, European, and South Asian) and body mass index range (<25, 25 to 29.9, or > or =30 kg/m(2)) were assessed for VAT (by computed tomography scan), carotid atherosclerosis (by ultrasound), total body fat, cardiovascular risk factors, lifestyle, and demographics. RESULTS: VAT was associated with carotid intima-media thickness (IMT), plaque area, and total area (IMT area and plaque area combined) after adjusting for demographics, family history, smoking, and percent body fat in men and women. In men, VAT was associated with IMT and total area after adjusting for insulin, glucose, homocysteine, blood pressure, and lipids. This association remained significant with IMT after further adjustment for either waist circumference or the waist-to-hip ratio. In women, VAT was no longer associated with IMT or total area after adjusting for risk factors. CONCLUSIONS: VAT is the primary region of adiposity associated with atherosclerosis and likely represents an additional risk factor for carotid atherosclerosis in men. Most but not all of this risk can be reflected clinically by either the waist circumference or waist-hip ratio measures.

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OBJECTIVE: To report the case of a gastric bezoar in a patient with anorexia nervosa (AN). METHOD: Case report of a bezoar of the stomach occurring in AN and a review of the literature relating to bezoars and AN from PubMed. RESULTS: A 19 year-old female presented with a 2-year history of AN binge-purge subtype. After 7 days of complete adherence to diet and no purging in hospital, she complained of increased nausea. She vomited up a cylindrical mass that was sent for pathology. A literature search yielded only one report of a bezoar in AN. DISCUSSION: Bezoars are agglomerations of food or foreign material in the intestine. They usually present with abdominal pain, intestinal obstruction, weight loss, poor appetite, or vomiting. The CT scan of the abdomen is the preferred method of diagnosis. Clinicians should consider the diagnosis of a bezoar in AN if there is concomitant pica, trichotillomania, or a change in gastrointestinal symptomatology.

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OBJECTIVE: To outline the study design of the Multicultural Community Health Assessment Trial (M-CHAT). The purpose of the study is to compare the relationship between visceral adipose tissue (VAT) and total body fat in men and women of Aboriginal, Chinese, and South Asian origin with a similar group of men and women of European origin. DESIGN: A total of 200 apparently healthy men and women between the ages of 30 and 65 will be recruited from each of the local Aboriginal, Chinese, and South Asian and European communities. Within each sex/ethnic group, an equal representation of participants will have a body mass index between 18.5 to 24.9, 25 to 29.9 and >30. Each participant will undergo an assessment for VAT, total body fat, metabolic risk factors, physical activity, diet, quality of life, and sociodemographics. MAIN OUTCOME MEASURES: The primary outcome of this study is the relationship between VAT and total body fat in each of the Aboriginal, Chinese, and South Asian cohorts; this relationship will be compared to the European cohort after adjustment for age, sex, socioeconomic status, smoking status, physical activity, diet, and body mass index. CONCLUSIONS: This study will be the first to identify differences in body fat distribution in these populations. We anticipate that in populations of Aboriginal, Chinese, and South Asian origin, a greater proportion of total body fat will be deposited as VAT compared to those of European origin.

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OBJECTIVE: We determined the standardized mortality ratio (SMR) in our anorexia nervosa (AN) patient population. METHOD: We used a cross-sectional design to study an inception cohort (1981-2000) drawn from the provincial tertiary care eating disorders program at St. Paul's Hospital (British Columbia, Canada). All patients who completed their initial assessment for an eating disorder were included in the study. Vital status, date and cause of death from British Columbia Vital Statistics Agency, date of assessment, date of birth, and diagnosis at the time of assessment were collected for each patient. RESULTS: Of 954 patients, 326 diagnosed with AN completed an assessment over the 20 years. The SMR was 10.5 (95% confidence interval [CI] = 5.5-15.5) for AN. DISCUSSION: Some studies in the literature report that AN has the highest mortality rate of any psychiatric disorder in young females. However, others dispute this fact and report an SMR lower than the normal population mortality (SMR = 0.71). Contrary to some reports in the literature, our study confirms a high mortality rate within the AN population.

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OBJECTIVE: To determine the prevalence of overweight adults living in the Bella Coola Valley. DESIGN: A retrospective chart review of all people attending the Bella Coola Medical Clinic, and residing in the Bella Coola Valley. MAIN OUTCOME MEASURES: Weight (killograms) and body mass index (BMI). RESULTS: More than 92% of clinic charts had a recent measurement of weight and 65% of clinic charts had height measured; accordingly, we were able to calculate the BMI on 65% of the clinic population. Over 50% of the adults residing in the Bella Coola Valley are considered overweight (BMI > 27, the Health Canada definition) and only 25% have a BMI within an acceptable range (20.0 to 24.9). Proportionately more Aboriginal people are overweight (65%) than non-Aboriginal people (47%); men and women were similarly overweight (56% and 53%, respectively); and proportionately more people were overweight with increased age. The prevalence of being overweight in people aged 65 years and older is 66%. As weight increased so did the prevalence of diabetes mellitus, hypertension, hypercholesterolemia, diverticular disease, dyspepsia/gastroesophageal reflux disease (GERD), alcohol issues, asthma, depression, coronary artery disease, and eczematous dermatitis. There was no relationship between increasing weight and atrial fibrillation, cerebrovascular disease, inflammatory arthritis, hypothyroidism, chronic back/neck pain, peripheral vascular disease, chronic obstructive lung disease, congestive heart failure, and cancer. CONCLUSION: Living in a remote community does not protect against obesity and the complications of obesity. Obesity is present in a greater proportion of Aboriginal people. The treatment and prevention of obesity in rural populations of differing ethnicity may need to be individualized.

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OBJECTIVE: We compared the natural history of bacterial infection in patients with anorexia nervosa (AN) with controls, and assessed which of a range of patient characteristics were associated with infection, fever response, and the rate of infectious complications in AN patients. METHOD: The charts of 311 consecutive hospital admissions of AN patients were reviewed. Patients who had a bacterial infection while in the hospital were compared with the AN patients who did not have an infection, with respect to a range of demographic and disease variables. Fever response and infection complication rate also were evaluated in AN patients with a bacterial infection and in nonanorectic control subjects admitted with a bacterial infection. RESULTS: AN patients with a bacterial infection showed a reduced fever response, were often difficult to diagnose because of fewer signs and symptoms, and infection became more frequent with increasing patient age. DISCUSSION: A reduction in fever response and the signs and symptoms of infection significantly delayed diagnosis in AN patients and increased the complication rate from bacterial infection. We recommend that an increased index of suspicion and an early complete blood count and bacteriologic cultures be adopted for the investigation of bacterial infection in AN patients.

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OBJECTIVE: Recovery from anorexia nervosa is confounded by intrusive anorectic cognitions and rituals. It has been observed that olanzapine, an atypical antipsychotic, can reduce this anorexic rumination. A pilot study was designed to test the effectiveness of olanzapine in this role. METHODS: A randomized trial of olanzapine versus chlorpromazine, with anorexic rumination as the primary outcome, was conducted. Of the 26 patients who presented, 15 were randomized in a balanced block design, eight to olanzapine and seven to chlorpromazine. RESULTS: Only the olanzapine group had a significant reduction in the degree of rumination. CONCLUSION: Olanzapine may be of benefit in anorexia nervosa by causing a reduction in anorexic rumination.

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