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Normal gastric antral myoelectrical activity in early onset anorexia nervosa.

Anorexia, epigastric discomfort, nausea, and vomiting may result from disordered gastric motility and emptying. These features have been found in many adults with anorexia nervosa, but have never been investigated in early onset anorexia nervosa. In 14 patients with early onset anorexia nervosa (eight of whom had upper gastrointestinal tract symptoms), six children with other eating disorders, four children with non-ulcer dyspepsia, and 10 controls matched for age and sex, the non-invasive technique of surface electrogastrography was used to measure fasting and postprandial gastric antral electrical control activity, which underlies antral motility. The electrical signal was recorded by four bipolar silver/silver chloride electrodes attached to the upper abdomen, amplified and low pass filtered at 0.33 Hz before being displayed on a polygraph, digitised at 1 Hz, and stored on the hard disk of a personal computer for later offline analysis. Patients with non-ulcer dyspepsia had gastric antral dysrhythmias. No significant difference was found in the mean (SD) dominant frequency of the antral electrical control activity between patients with early onset anorexia nervosa (2.86 (0.35) cycles/minute (cpm)), patients with other eating disorders (3.14 (0.65) cpm), and controls (3.00 (0.46) cpm). The amplitude of electrical control activity increased postprandially in all but one subject and the fasting/postprandial amplitude ratio did not significantly differ between patients with early onset anorexia nervosa and controls, though patients with longer established disease had a smaller increase in amplitude. Gastric antral electrical dysrhythmias are not a feature of early onset anorexia nervosa and therefore do not induce or perpetuate food refusal in this disorder.

Adolescent↗

Genetic factors in anorexia nervosa.

Anorexia nervosa is a severe and complex disorder with incompletely known vulnerability factors. It is generally recognized that anorexia nervosa is a familial disorder, but the majority of twin studies have shown that the concordance rate for monozygotic twins is higher (on average 44%) than for dizygotic twins (on average 12.5%). This difference in concordance rates shows that genetic factors, more than common familial environment, may explain why the 'anorexia nervosa' phenotype runs in families. In order to estimate the heritability in the broad sense of anorexia nervosa according to published familial and twin studies, we first assessed the intrapair correlation between monozygotic and dizygotic twins, and secondly calculated the deviation threshold of relatives of affected probands from the relative mean. In this review, we obtained an estimation of the heritability at 0.72 according to all published controlled familial studies (six references quoted in MEDLINE(R)), and 0.71 for all published twin studies (59 references quoted in MEDLINE(R)). This estimation is close to the ones previously proposed, between 0. 5 and 0.8. Familial and twin studies may also help to define the boundaries of the phenotype, shedding light on the complex relationship between anorexia nervosa on the one hand, and bulimia nervosa, mood disorders, and alcoholism on the other. Demonstrating the importance of genetic factors in anorexia nervosa, and more specifically for anorexia of the restrictive type, requires not only prospective and adoption studies (which are still lacking), but also genetic polymorphisms analyses, which began very recently.

Anorexia Nervosa↗

Cutaneous manifestations in anorexia nervosa.

Anorexia nervosa is an eating disorder among adolescent girls and young women which, though common, often goes undetected and untreated. Anorexia nervosa is a response for young people with psychological conflicts who try to win love by having a body corresponding to the present-day image, symbolising strength, beauty, attraction, power and success. Anorexia nervosa involves inadequate calorie intake leading to marked cachexia with metabolic and endocrinological disturbances. We investigated dermatological changes in 21 young female anorectics aged 19-24 in an attempt to find dermatological markers which mirror the dynamics of the disease and thus obtain helpful signs for early diagnosis with its important bearing on the outcome. Extensive histories were taken and whole-body examinations performed. Seven sex- and age-matched persons served as a control group. The most common dermatological findings were xerosis (71%, controls 29%), cheilitis (76%), bodily hypertrichosis (62%), alopecia (24%), dry scalp hair (48%), acral coldness (38%), acrocyanosis (33%), periungual erythema (48%), gingival changes (37%), nail changes (29%) and calluses on dorsum of hand due to self-induced vomiting (67%). Our study documented for the first time that a body mass index of < or = 16 (kg/m2) can be considered a critical value at which skin changes are more frequent. There are remarkable similarities between cutaneous manifestations in anorexia nervosa and in HIV infection. Patients with anorexia nervosa develop early stereotype skin changes which are cardinal diagnostic symptoms and pointers to the diagnosis of eating disorders. During training at the Department of Child and Adolescent Psychiatry in Solothurn one of us (C. H.) was once more able to observe most of the above-described cutaneous and mucocutaneous changes in anorexic adolescents. This paper is intended to stimulate further basic research on this topic. We hope our study will facilitate early diagnosis of anorexia nervosa by the family physician and enable him or her to institute immediate treatment for the eating disorder and thereby improve the prognosis.

Adolescent↗

Steroids and neuroendocrine function in anorexia nervosa.

Anorexia nervosa is a primarily psychiatric syndrome of self-induced weight loss due to an intense fear of becoming obese. Numerous endocrine abnormalities occur in anorexia nervosa patients, and in many respects these alterations reflects the endocrinology of reduced energy intake. However, the basic mechanisms of those alterations are far from being understood. In an attempt to understand the disrupted mechanisms of the hypogonadotropic hypogonadism of the anorectic state, we studied 10 anorectic women in the acute phase of their illness; all met the DSM III criteria. On each patient, two tests were performed with either saline as control or infusion of the opioid antagonist naloxone, and both LH and FSH levels were measured. Four mg of naloxone as bolus was used, followed by a naloxone infusion of 2 mg/h for 4 h. Compared with the pattern of normal women, naloxone did not increase in the anorectic patients either LH or FSH levels nor pulsatility. This result suggests that endogenous opioid peptides are not implicated in the low gonadotropic situation of anorexia nervosa. An alternative explanation could be that the low estrogenic "milieu" of these patients could mask the opioid action. To test this second possibility, another group of 7 anorectic women after partial weight recovery were challenged with estrogen administration. Compared with the pattern of normal women volunteers, all the anorectic patients but one presented an abnormal response in both LH and FSH levels after estrogen administration. In fact, the negative feedback and the delayed positive feedback of LH after estrogen were absent in these patients. Interestingly enough, the only patient with near-normal LH response to estrogen was considered fully recovered by the Psychiatric Unit. Several alterations in the hypothalamic-pituitary-adrenal axis has been reported in anorexia nervosa. Seven anorectic patients and 7 aged-matched women were challenged by ACTH 1-24, 250 micrograms (i.v.) and the ratio of increments in adrenal steroid products to precursors monitored. ACTH-induced increments in cortisol with respect to increments in 17-OH-progesterone was similar in anorectics and controls. On the contrary, the ratio of increments of androstenedione with respect to increments in 17-OH-progesterone were greater in anorexia nervosa than controls. These results suggest that in anorexia nervosa the 11-beta-21-alpha-hydroxylase system is normal but a deficient 17-20 desmolase system is present. Finally, the altered pattern of GH secretion in anorexia was studied using GHRH (1 microgram/kg) as stimulus of pituitary GH secretion.(ABSTRACT TRUNCATED AT 400 WORDS)

Amenorrhea↗

Hematologic and metabolic abnormalities in a patient with anorexia nervosa.

Anorexia nervosa is a common problem in young adults that may present with a variety of metabolic and hematologic abnormalities, as well as weight loss and psychological disturbances. We present a young man with a long history of anorexia nervosa who developed pancytopenia associated with decreased bone marrow cellularity and abnormal architecture and marrow infiltration with an amorphous, gelatinous substance characteristic of anorexia nervosa. The patient also developed osteopenia with evidence of excessive calcium excretion. The pancytopenia and marrow function reverted to normal with therapeutic and dietary intervention. The effects of eating disorders can result in serious consequences with respect to an individual's health and well-being. A host of hematologic abnormalities that are associated with anorexia nervosa have the potential of increasing the risk of infection and bleeding. Additionally, because of the insidious development of anemia in some patients, decreased performance status and chronic fatigue can pose significant compromises in one's daily activities and work effort. Anorexia nervosa is a chronic illness that is distinctly more common in females than in males (ratio of 10 to 1), but can affect males in an equally debilitating manner, requiring multiple modalities of therapeutic intervention and consultation. We present the case of a male referred to the hematology department because of pancytopenia, chronic fatigue, and back pain. A diagnosis of anorexia nervosa had been made 10 years prior at the age of 18 years.

Adult↗

Anesthetic considerations with anorexia nervosa.

Anorexia nervosa is a chronic illness characterized by a severe loss of weight. It occurs in children and young adults and is seen more frequently in females. Some anorexic patients refuse to eat totally, while others may practice "binge eating." Patients who binge eat and employ postprandial purging are referred to as "bulimic." Anorexia nervosa and bulimia can produce multisystem abnormalities. Dysfunction of organ systems in anorexia is the result of self-induced vomiting, laxative abuse, and severe malnutrition. Diseases of the skeletal, gastrointestinal, pulmonary, endocrine, and cardiovascular systems may have an impact on the plan of anesthesia care. A thorough anesthetic interview and evaluation to assess the debilitation of each patient is essential so that appropriate preparation can be made for comprehensive anesthetic care. This paper focuses on the pathophysiology of anorexia nervosa, discusses a thorough preanesthetic assessment, and guides the appropriate anesthetic management of the anorexic patient. Anorexia bulimia is briefly mentioned, since it is an eating disorder with physiological derangements similar to anorexia nervosa.

Adolescent↗

Unusual accumulation of glycogen in liver parenchymal cells in a patient with anorexia nervosa.

Anorexia nervosa is an eating disorder characterized by a fear of weight gain and a preoccupation with body image. Although hepatic involvement has been reported in patients with anorexia nervosa, the mechanism is not fully understood. We describe a patient with anorexia nervosa with liver function abnormalities. Light and electron microscopic observations revealed a remarkable accumulation of glycogen in hepatocytes. These results suggest that adaptive responses to starvation may alter carbohydrate metabolism in patients with anorexia nervosa.

Adult↗

Composition of plasma fatty acids and non-cholesterol sterols in anorexia nervosa.

Anorexia nervosa is a model of simple starvation accompanied by secondary hyperlipoproteinemia. The pattern of plasma fatty acids influences the levels of plasma lipids and lipoproteins. The concentration of plasma lathosterol is a surrogate marker of cholesterol synthesis de novo, concentrations of campesterol and beta-sitosterol reflect resorption of exogenous cholesterol. The aim of the study was to evaluate fatty acids in plasma lipid classes and their relationship to plasma lipids, lipoproteins, cholesterol precursors and plant sterols. We examined 16 women with anorexia nervosa and 25 healthy ones. Patients with anorexia nervosa revealed increased concentrations of total cholesterol, triglycerides, HDL-cholesterol, campesterol and beta-sitosterol. Moreover, a decreased content of n-6 polyunsaturated fatty acids was found in all lipid classes. These changes were compensated by an increased content of monounsaturated fatty acids in cholesteryl esters, saturated fatty acids in triglycerides and both monounsaturated and saturated fatty acids in phosphatidylcholine. The most consistent finding in the fatty acid pattern concerned a decreased content of linoleic acid and a raised content of palmitoleic acid in all lipid classes. The changes of plasma lipids and lipoproteins in anorexia nervosa are the result of complex mechanisms including decreased catabolism of triglyceride-rich lipoproteins, normal rate of cholesterol synthesis and increased resorption of exogenous cholesterol.

Adult↗

Role of interleukin-6 and transforming growth factor-beta in anorexia nervosa.

Anorexia nervosa is a serious eating disorder characterized by extreme weight loss and abnormalities of the neuroendocrine and immune systems. To determine the potential role of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and transforming growth factor-beta (TGF-beta) in anorexia nervosa, serum concentrations of these cytokines were measured in patients with anorexia nervosa during starvation and after weight gain. Serum IL-6 and TGF-beta concentrations were both significantly elevated during starvation and returned to levels comparable to those of normal-weight controls by the end of therapy. In contrast, serum TNF-alpha levels were undetectable in all patients and controls. Cytokines may play previously unsuspected roles in anorexia nervosa and its complications.

Adolescent↗

Single nucleotide polymorphisms in the leptin receptor gene: studies in anorexia nervosa.

Anorexia nervosa is an eating disorder of unknown aetiology. There is significant evidence for a genetic component in the pathogenesis of this disorder. A region on chromosome 1 has been identified as a susceptibility locus. The leptin receptor has been mapped to a similar region, further upstream of this susceptibility locus. Leptin and its receptor are known to be important factors in the control and regulation of body weight. Single nucleotide polymorphisms (SNPs) in the leptin receptor are associated with measures of body weight. In the present study, SNPs in the coding region of the leptin receptor were analysed and their possible association with anorexia nervosa was investigated. Two cohorts of young women, 176 Caucasian anorexia nervosa patients and 152 normal Caucasian females, were genotyped for three SNPs in the leptin receptor. There was no significant difference in allele or genotype frequency, for any SNP, between the normal controls and the cohort of anorexia subjects. There were no significant associations with any genotype and body mass index in either the control or anorexic cohorts. When the anorexic cohort was subdivided into restricting and bingeing/purging behaviours, we found no significant association with any genotype. Analysis of haplotypes showed no significant evidence of association with anorexia. In summary, leptin receptor SNPs do not appear to be important factors in the regulation of body weight in young, pre-menopausal women or have any significant association with anorexia nervosa.

Adult↗

Compliance and outcome in anorexia nervosa.

Anorexia nervosa is notoriously difficult to treat, but little is known regarding the relationship of compliance to treatment outcome. We investigated in 41 adolescents who fulfilled DSM-III-R criteria for anorexia nervosa, the relationship between the completion of a standard psychosocial treatment program, subtypes of anorexia nervosa, and outcome as determined by standardized measurements. These adolescents were observed for an average of 32.4 months. Overall, 29 patients (70%) improved considerably, but 10 (24%) were symptomatic, and 2 (5%) remained in poor condition. There were no deaths. Of the 41 patients, 14 (34%) completed our entire treatment program, 15 (37%) received major treatment and failed in the outpatient follow-up phase only, 7 (17%) dropped out of inpatient treatment before its completion, and 5 (12%) refused treatment in our system altogether. Of all the dropouts, 10 received no further treatment. One patient was admitted to hospital elsewhere but again dropped out in the outpatient phase of that program. Seven patients (17%) received further outpatient treatment only, and 9 (22%) received inpatient and outpatient care and seemingly completed their treatment. Treatment completion significantly affected the measures of global clinical functioning and specific psychopathologic features, but only for those patients who completed the initial program. Bulimic patients did considerably worse on follow-up and were less likely to complete treatment. Patients with restricted anorexia nervosa were more likely to complete treatment than those with a bulimic subtype (P = .03). Differential compliance rates in the two subtypes confound the effects of treatment completion and need to be controlled for in future studies. Depression was not associated with noncompliance but, if present, was associated with poor outcome on follow-up and abated in only a third of those in whom it was initially present.

Adolescent↗

Basal activity of the hypothalamic-pituitary-adrenal axis and cognitive function in anorexia nervosa.

Anorexia nervosa is associated with abnormalities in neuroendocrine function including sustained hypercortisolism, which has been shown elsewhere to be associated with impairment of function in learning, memory and attention. Cognitive impairment has also been observed in anorexia nervosa. These effects may be mediated in part through cortisol effects on the hippocampus, which is dense with glucocorticoid receptors. We investigated the association between cortisol levels and cognitive function in anorexia nervosa by measuring both 24-hour urinary cortisol counts and performance on tasks of learning, memory and attention in patients suffering from the disorder. Cortisol secretion was shown to be significantly higher in the patient group than in a matched control group and patients were also shown to be impaired in memory and attention. However, no correlations were found between the cognitive deficits and cortisol measures. It is suggested that more sensitive profiling of cortisol levels throughout the circadian cycle may be useful in future studies of cognitive function in anorexia nervosa.

Adult↗

[Genetic factors in the etiology of anorexia nervosa].

Anorexia nervosa (AN) is a disease of complex ethiopatogenesis. Population genetics studies suggest a significant role of genetic factors in the morbidity risk. Family and twin studies allow for the estimation of the heritability--the influence of genetic factors on the specific phenotype--of the anorexia nervosa in 50-80%. Due to the low prevalence of the disease, the adoption studies have not been performed. The rapid development of the molecular biology methods gives possibility for the searching of the specific genes increasing the risk of anorexia nervosa. Linkage studies are based on scanning the whole genome for loci associated with susceptibility to a certain disease. In the preliminary studies, no linkage was found between anorexia nervosa and the markers on the chromosomes 1-5, 13 and X. In the association studies, relationship between vulnerability to AN and polymorphism in 5-HT2a receptor and uncoupling proteins gene were reported. These results need further confirmation.

Anorexia Nervosa↗

A review of endocrine changes in anorexia nervosa.

Anorexia nervosa is a syndrome of unknown etiology. It is associated with multiple endocrine abnormalities. Hypothalamic monoamines (especially serotonin), neuropeptides (especially neuropeptide Y and cholecystokinin) and leptin are involved in the regulation of human appetite, and in several ways they are changed in anorexia nervosa. However, it remains to be clarified whether the altered appetite regulation is secondary or etiologic. Increased secretion of corticotropin-releasing hormone and proopiomelanocortin seems to be secondary to starvation, however, there is evidence that it may maintain and intensify anorexia, excessive physical activity and amenorrhea. Hypothalamic amenorrhea, which is a diagnostic criterion in anorexia nervosa, is not solely related to the low body weight and exercise. Growth hormone resistance with low production of insulin-like growth factor I and high growth hormone secretion reflect the nutritional deprivation. The nutritional therapy of patients with anorexia nervosa might be improved by administering an anabolic agent such as growth hormone or insulin-like growth factor I. So far none of the endocrine abnormalities have proved to be primary, however, there is increasing evidence that some of these might participate in a vicious circle.

Anorexia Nervosa↗

MicroPET imaging in an animal model of anorexia nervosa.

Anorexia nervosa is a life-threatening psychiatric disorder characterized by severe weight loss and high rates of comorbidity and mortality. The current study assessed the feasibility of using microPET imaging to study the effects of chronic food restriction in an animal model of anorexia nervosa. To establish preliminary support for this model, we hypothesized that chronic food restriction would decrease relative 2-deoxy-2-[18F]fluoro-D-glucose (18FDG) uptake in the rat, in effect modeling cerebral glucose hypometabolism reported in the clinical population of anorexia nervosa. Nine adolescent Wistar female rats received a baseline 18FDG scan. The control group received free access to food for a period of 25 days. The food restricted (FR) group received 40% of their baseline daily food intake until a 30% weight loss occurred; body weight was then maintained at 70% of baseline by adjusting daily food intake. The FR group also had free access to a running wheel for a mean period of 10.8+/-6.1 days. Both groups received a follow-up 18FDG scan. Relative 18FDG uptake was significantly increased in the cerebellum and significantly decreased in the hippocampus and striatum in the FR group compared to controls. Moreover, there was a trend towards a decrease in relative 18FDG uptake in the thalamus in the FR compared to control group. This is the first study to establish support for the use of microPET imaging in an animal model of anorexia nervosa as a means for studying the neurobiological changes that occur due to chronic food restriction.

Animals↗

[Sinus bradycardia in anorexia nervosa].

Anorexia nervosa is a frequent condition of malnutrition in industrialized countries. The most frequent causes of death in patients with anorexia nervosa are suicide and sudden death generally in relationship with cardiovascular abnormalities. We report a case of a 42-year-old woman with anorexia nervosa who was admitted to our hospital because of severe weight loss. Her electrocardiogram showed a severe sinus bradycardia of 27 b/min.

Adult↗

Gelatinous degeneration of the bone marrow in anorexia nervosa.

Anorexia nervosa is a chronic psychiatric process characterized by a restrictive disorder in alimentary habits. Hematologic alterations in the peripheral blood include cytopenias involving one or more hematopoietic lineages. Morphologic changes in the bone marrow and stereologic alterations in bone marrow adiopocytes may also be observed in anorexia nervosa. We present a 12-year-old girl who had chronic anorexia and one third of body weight loss during an 8-month period. She was apathetic and had missed several menstrual cycles. The sex maturity rating was Tanner stage IV. There was no lymphadenopathy, no hepatosplenomegaly, and no identifiable tumor mass. She was not anemic, but was found to have leukopenia, neutropenia and a low level of triiodothyronine. Sections of the bone marrow biopsy showed almost complete serous atrophy (gelatinous degeneration) of the bone marrow. In this patient, the bone marrow alteration is related to nutritional deprivation of anorexia nervosa.

Anorexia Nervosa↗

Diagnosis and treatment of anorexia nervosa.

Anorexia nervosa is much like other psychogenic or psychosomatic disorders in that it tends to run a chronic, relapsing course, with a proportion of patients never fully recovering. It is unlike them, however, in that significant mortality rates have been reported. With epidemiological studies now suggesting an increased incidence of the disorder, and follow-up studies indicating the importance of early treatment to favorable outcome, the vital role of family physicians in diagnosis and treatment becomes evident. This paper draws on both published accounts and original case material to summarize the primary diagnostic criteria and secondary signs of anorexia nervosa. An illustrative history of a young woman with chronic anorexia nervosa is followed by a discussion of treatment alternatives. Although still in the experimental stage, behavior therapy is presented for its apparent efficacy and adaptability to the outpatient family practice setting.

Adolescent↗