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Biomedical subjects

C M Hadigan

Publications and source records attributed to C M Hadigan.

11 recordsLinked to original sources

Regulation of adiponectin in adipocytes upon exposure to HIV-1.

OBJECTIVES: Adipose dysregulation, dyslipidemia, and insulin resistance are hallmarks of HIV-related lipodystrophy. The precise mechanisms behind these disturbances are unknown. In HIV-infected patients, we previously demonstrated a strong relationship between lipodystrophy and levels of adiponectin, an adipose peptide implicated in regulation of glucose and lipid metabolisms. In this study we investigated the effect of HIV on adipocytes, to determine whether HIV can directly infect adipocytes and/or alter the regulation and secretion of the adipocyte-derived hormone adiponectin. METHODS: Human subcutaneous preadipocytes and adipocytes were exposed to HIV-1 under various conditions. Adiponectin was measured in supernatants and cell lysates. RESULTS: Although adipocytes expressed CD4, the major HIV receptor, they could not be infected in vitro. However, exposure to HIV dramatically increased the secretion of adiponectin from human adipocytes, in the absence of infection. This was exacerbated with sustained exposure to HIV in a transwell assay. Further, human peripheral mononuclear cells also produced adiponectin, but this was largely dependent upon T-cell activation. CONCLUSIONS: We propose that the stimulation of adiponectin production by HIV can perturb adiponectin regulation, leading to substantially decreased levels upon viral suppression by antiretroviral therapy. These data suggest a potential molecular mechanism of adiponectin regulation in HIV-infected patients.

Adipocytes↗

Increased abdominal visceral fat is associated with reduced bone density in HIV-infected men with lipodystrophy.

OBJECTIVE: To examine the relationship between bone density and changes in regional and whole body composition in HIV-infected men with and without lipodystrophy. DESIGN: Cross-sectional, observational study of HIV-infected men with and without lipodystrophy and matched HIV-negative controls. SETTING: Tertiary care academic medical institution. PATIENTS: A total of 59 men, belonging to three different groups: HIV-positive men with lipodystrophy (n = 21), HIV-positive men without lipodystrophy (n = 20), and age-matched and body mass index-matched HIV-negative controls (n = 18). METHODS: Bone density, markers of bone turnover and indices of calcium metabolism were measured in all subjects. Quantitative computed tomography was used both to determine volumetric bone density of the spine and to quantify abdominal visceral fat. Dual energy X-ray absorptiometry was used to determine whole body composition and bone density. Statistical comparisons were performed according to lipodystrophy categorization and protease inhibitor exposure. RESULTS: Men with HIV-associated lipodystrophy had reduced lumbar spine bone density compared with both HIV-infected non-lipodystrophic men [mean +/- SD, 132 +/- 29 versus 154 +/- 30 mg/cm(3); P = 0.02] and HIV-negative controls [mean +/- SD 132 +/- 29 versus 148 +/- 18) mg/cm(3); P = 0.04]. Lumbar spine bone density was reduced significantly in HIV lipodystrophy patients independently of protease inhibitor use. In an analysis among all HIV-infected subjects, increased visceral abdominal fat area was associated with decreased lumbar spine bone density (r, -0.47; P = 0.002). The association between visceral fat and bone density remained significant (P = 0.007) after controlling for age, body mass index, lowest body weight, protease inhibitor use, and extremity fat in a multivariate regression model. Markers of bone turnover were not related to bone density or lipodystrophy status. CONCLUSIONS: Lumbar spine bone density is reduced in association with increased visceral fat in HIV-infected men with lipodystrophy. Further studies are needed to determine the mechanisms of osteopenia in HIV lipodystrophy and whether increased marrow fat occurs in such patients and affects bone density.

Absorptiometry, Photon↗

Assessment of macronutrient and micronutrient intake in women with anorexia nervosa.

OBJECTIVE: The purpose of this study is to evaluate the accuracy of diet history compared to observed food intake in the nutritional assessment of women with anorexia nervosa (AN) and healthy age-matched controls. METHOD: One-month diet history was compared to 1-day observed food intake in 30 women with AN and 28 control subjects. RESULTS: Reported intake by diet history was similar to observed intake for macronutrient composition and fat intake for patients with AN. Reported energy intake was higher than observed intake (1,602 +/- 200 kcal vs. 1,289 +/- 150 kcal, p <.05), but was in agreement with predicted energy expenditure by the Harris-Benedict equation (1,594 +/- 18 kcal, p =.97) in patients with AN. Micronutrient intake by diet history was highly correlated with observed intake in patients with AN. More than one half of the patients with AN failed to meet the recommended dietary allowance (RDA) for vitamin D, calcium, folate, vitamin B12, zinc, magnesium, and copper when assessed by diet history. In contrast to patients with AN, diet history did not correlate with observed intake of energy, macronutrients, or most micronutrients among the controls. DISCUSSION: Diet history is an accurate tool to assess fat intake and macronutrient composition in patients with AN and demonstrates significant micronutrient deficiencies in this population. The agreement between total energy intake and predicted energy expenditure supports the overall utility of the diet history in the nutritional assessment of patients with AN.

Adolescent↗

Behavioral and neuroendocrine responses to metaCPP in anorexia nervosa.

In response to the partial serotonin agonist meta-chlorophenylpiperazine (metaCPP), patients with obsessive-compulsive disorder have been reported to exhibit an increase in obsessive symptoms and a diminished release of prolactin and/or cortisol compared to controls. We examined the response to metaCPP of 10 patients with anorexia nervosa, before and after weight gain, and of eight healthy controls. Prior to weight gain, the patients exhibited a greater behavioral response to metaCPP than the controls and diminished prolactin and cortisol responses. Only the prolactin abnormality persisted after weight gain. These observations suggest that, in patients with anorexia nervosa, weight loss is associated with the development of neurobiological disturbances which are in some ways similar to those of obsessive-compulsive disorder.

Adult↗

The single-item meal as a measure of binge-eating behavior in patients with bulimia nervosa.

To determine whether the characteristics of binge eating could be observed in a single-item meal, in a laboratory, patients with bulimia nervosa and controls ate two single-item meals and two multiple-item meals. When they were instructed to binge eat, the patients ate significantly more and for a longer time on both single- and multiple-item meals than did controls. When they were instructed not to binge, intakes of the two groups did not differ. Controls, but not most of the patients, showed deceleration in their eating rate when they were asked to binge. Intakes of the single- and multiple-item meals were significantly correlated for the patients under both sets of instructions. These results are consistent with previous reports in indicating that patients with bulimia nervosa eat differently from controls and suggest that a single-item meal can be used to examine the characteristics of binge eating in patients with bulimia nervosa.

Adult↗

Behavioral assessment of satiety in bulimia nervosa.

The abnormalities in eating behavior associated with bulimia nervosa suggest that patients with this illness may have a disturbance in satiety. The present study employed a six-meal protocol to assess satiety in both binge and non-binge eating episodes in women with bulimia nervosa and normal controls by examining whether an increase in the size of a soup preload led to a decrease in the amount of food consumed in a subsequent test meal. In control subjects, the increase in preload size was associated with an increase in fullness and a reduction in consumption of the non-binge test meal. Patients did not report consistent changes in ratings of hunger and fullness in response to the change in preload size, and few patients were able to complete the non-binge meals and refrain from vomiting afterwards. When instructed to binge eat, patients ate considerably more than control subjects, but patients did significantly reduce their intake of the test meal after the large compared to the small preload. These findings demonstrate that, although patients with bulimia nervosa exhibit abnormalities in the development of satiety, some mechanisms responsible for the control of food intake are functional during binge eating episodes.

Adolescent↗

Increased pulse and blood pressure associated with desipramine treatment of bulimia nervosa.

The cardiovascular effects of desipramine were assessed in 74 young women with bulimia nervosa participating in a 6-week double-blind, placebo-controlled study. Desipramine treatment was associated with significant increases in pulse, reclining systolic and diastolic blood pressures, and orthostatic hypotension. These effects were clearly evident in the first week of treatment and remained relatively unchanged during the subsequent 5 weeks. The mean increases in reclining systolic and diastolic pressures were approximately 10 mm Hg. Data from 16 patients treated for an additional 2 months indicated that most of the effects of desipramine on blood pressure diminished over time, whereas the effects on pulse persisted. These results differ from the commonly expected cardiovascular effects of tricyclic anti-depressants in adults. Evidence from the current study and from other reports suggests that the cardiovascular effects of tricyclic antidepressants are age-dependent.

Adolescent↗

Long-term outcome of antidepressant treatment for bulimia nervosa.

OBJECTIVE: The purpose of this study was 1) to replicate previous work indicating that antidepressant medication is superior to placebo in the treatment of bulimia nervosa and 2) to assess the long-term efficacy of this form of treatment. METHOD: Eighty patients entered a three-phase treatment protocol. An 8-week double-blind initiation phase was used to compare the effects of desipramine and placebo. Patients who responded satisfactorily to desipramine entered a 16-week maintenance phase. Patients who remained well were then randomly assigned to either desipramine or placebo for 6 additional months (discontinuation phase). The primary outcome measure was binge frequency, which was assessed weekly by self-report diaries. RESULTS: In the initiation phase the superiority of desipramine over placebo in reducing binge frequency was demonstrated. Patients treated with desipramine had a mean reduction in binge frequency of 47% at termination, whereas patients taking placebo experienced a mean increase of 7%. Less than half of the patients treated with desipramine met the criteria for entering the maintenance phase, and 29% of the patients entering that phase relapsed in the following 4 months. There were not enough patients in the discontinuation phase to permit clear conclusions about the need for continued antidepressant medication after 6 months of treatment. CONCLUSIONS: The study documents a beneficial effect of desipramine in the treatment of bulimia nervosa when compared to placebo. However, limited improvement and considerable relapse with continued treatment suggest serious limitations to the long-term efficacy of a single antidepressant trial in treating bulimia nervosa.

Adult↗

Hyperamylasemia in bulimia nervosa.

To determine the value of total serum amylase levels and salivary and pancreatic isoenzyme levels as biologic indices of behavioral disturbance in bulimia nervosa, the authors monitored these levels in 40 bulimic patients participating in a placebo-controlled trial of desipramine and in 25 controls. In the patients, the total and salivary amylase levels were significantly elevated and a significant correlation existed between the frequencies of binge eating and vomiting and the level of salivary amylase. However, the ability to discriminate patients from controls on the basis of serum amylase levels was limited. In addition, a significant positive relationship between binge frequency and level of serum amylase was observed in less than one quarter of 22 patients with five or more amylase determinations. Therefore, although hyperamylasemia is associated with bulimia nervosa, we believe that serum amylase determinations have limited utility in the assessment of patients with this syndrome.

Adolescent↗

Patterns of food selection during meals in women with bulimia.

Eating behavior of women with bulimia was compared with that of control subjects who had no eating disorders. Both groups were presented with two buffet-style multiple-item meals. In one meal subjects were instructed to eat normally and in the other they were instructed to eat as much as they could. The eating patterns of patients differed from control subjects in the quantity of food selected and in the rate of eating. During the binge meal, patients spent more of their meal time eating dessert and snacks than did control subjects and began their dessert and snack consumption earlier than control subjects. Patients distributed their meat consumption more evenly across the meal, whereas control subjects ate meat predominantly early in the meals. Most patients consumed either more or less than control subjects when not binge eating, indicating that the eating disturbances in bulimic patients are not confined to episodes of binge eating.

Adult↗

Eating behavior in bulimia.

Despite our strong belief in the utility of laboratory studies of eating behavior, we also note several caveats on the data thereby obtained. First, it must be assumed that subjects' behavior is influenced by the laboratory environment and is not identical to eating behavior in a "normal" setting. Second, not all bulimic subjects who were screened for these studies actually participated, so that it is possible that the sample of patients from whom we obtained data differed in some ways from a general clinical population of women with bulimia. Nonetheless, we believe that our data provide compelling evidence that the disturbed eating behavior characteristic of bulimia nervosa can be profitably studied in the laboratory. Even under structured laboratory conditions, most bulimic patients rated one of their multicourse meals as typical of a binge, and, during that meal, consumed a much larger amount of food and ate more rapidly than did controls who were asked to overeat. The significant correlations between the sizes of the multicourse and single-course binge meals and between the size of laboratory binge meals and the size of the "naturally occurring" binge meals reported to the dietician suggest that a reproducible phenomenon is being examined. The results of our studies suggest that the abnormalities of eating behavior in bulimia nervosa cannot be viewed simply as a disturbance of carbohydrate consumption or even as the episodic consumption of a certain type of food. Rather, eating behavior in this syndrome appears more generally disturbed. The most striking difference between the binge and the nonbinge meals of bulimic patients and between the binge eating of patients and the overeating of normal persons is the amount of food consumed, not the macronutrient composition of the meals. In addition, for all four meal types, the patients were hungrier after the end of the meal than were the controls, even though the patients' average caloric intakes were generally larger and their average hunger ratings before the meals did not differ from those of the controls. Certainly, self-induced vomiting may contribute to this abnormality, but it was also observed after nonbinge meals when vomiting did not occur. Together, these data are consistent with the notion that the essential appetitive abnormality in bulimia nervosa lies in the control of the amount of food consumed, not in the consumption of a particular macronutrient or type of food. Patients with bulimia nervosa appear less responsive than normal to the signals that lead to the termination of a meal.(ABSTRACT TRUNCATED AT 400 WORDS)

Body Weight↗