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Structural brain abnormalities in patients with bulimia nervosa.

Computed tomographic (CT) brain scans were performed in 50 inpatients with bulimia nervosa, 50 anorectic inpatients, and 50 age-matched control subjects. A number of patients with bulimia nervosa had enlarged ventricles and/or sulcal widening, but the degree and frequency of ventricular dilatation and sulcal widening were not so pronounced as in patients with anorexia nervosa. As the bulimic patients were of normal body weight, the CT abnormalities cannot be attributed to emaciation, which has often been suggested as the cause of abnormalities found in anorectic patients. Since many bulimic patients repeatedly attempt to lose weight by going on restrictive diets, the morphological brain alterations may reflect the endocrine and metabolic reactions to starvation--regardless of whether starvation has led to emaciation, as in the case of anorexia nervosa, or only counterbalanced the binges of high-caloric food. This assumption is supported by the finding that in both bulimic and anorectic patients ventricular size is inversely correlated with the plasma levels of triiodothyronine, a low concentration of which is an indicator for starvation.

3-Hydroxybutyric Acid↗

Hypothalamic-pituitary-gonadal function in anorexia nervosa and bulimia.

Patients with anorexia nervosa (AN) exhibit neuroendocrine abnormalities that may result solely from emaciation or may reflect defective endocrine mechanisms which are intrinsic to disordered eating even in the absence of starvation. To distinguish these possibilities, we have studied indices of hypothalamic-pituitary-gonadal (HPG) function in 9 patients with AN, 12 normal weight patients with bulimia and recent or current oligomenorrhea, and 8 normal weight controls. Measurement of 24-hour luteinizing hormone (LH) secretion with 30-min sampling revealed significantly fewer LH secretory spikes and a trend toward lower mean 24-hour LH levels in both bulimic and anorectic patients than in controls. Stimulation with gonadotropin releasing hormone produced elevated LH responses in the bulimic group and blunted LH responses in the anorectic group. Stimulation with estradiol revealed diminished LH augmentative responses and a trend toward diminished follicle stimulating hormone augmentative responses among bulimic as well as AN patients compared to controls. In each instance, the bulimic group tended to show within-group heterogeneity, with some individuals falling within the AN range. These findings suggest that HPG axis abnormalities in eating disordered patients cannot entirely be attributed to emaciation and that factors other than subnormal weight contribute to disturbed hypothalamic-pituitary functioning in these patients.

Amenorrhea↗

Animal immunodeficiency viruses.

Feline immunodeficiency virus (FIV) has morphological, physical and biochemical characteristics similar to human immunodeficiency virus (HIV), the cause of AIDS in man. However, it is antigenically and genetically distinct from HIV; an antigenic relatedness with equine infectious anaemia virus has been demonstrated. FIV has been molecularly cloned and sequenced. Diagnostic tests are commercially available and attempts at preparing inactivated, subunit and molecularly engineered vaccines are being made in different laboratories. During FIV infection a transient primary illness can be recognized, with fever, neutropenia and lymphadenopathy. After a long period of clinical normalcy a secondary stage is distinguished with signs of an immunodeficiency-like syndrome. The incubation period for this stage can be as long as 5 years, during which gradual impairment of immune function develops. Many FIV-infected cats are presented for the first time showing vague signs of illness: recurrent fevers, emaciation, lack of appetite, lymphadenopathy, anaemia, leucopenia and behavioural changes. Later, the predominant clinical signs observed are chronic stomatitis/gingivitis, enteritis, upper respiratory tract infections, and infections of the skin. Neoplasias, neurological, immunological and haematological disorder are seen in a smaller proportion. The immunodeficiency-like syndrome is progressive over a period of months to years. Concomitant infection with feline leukaemia virus has been shown to accelerate the progression of disease. In vitro, phenotypic mixing between FIV and an endogenous feline oncovirus (RD114) has been demonstrated which leads to a broadening of the cell spectrum of the lentivirus. Bovine immunodeficiency virus (BIV) has been isolated only once, and all attempts to obtain additional isolates have failed; it has been recovered from the leucocytes of cattle with persistent lymphocytosis, lymphadenopathy, lesions in the central nervous system, progressive weakness and emaciation. As with the feline representative, BIV also was found to possess a lentivirus morphology and to encode a reverse transcriptase with Mg++ preference; it replicates and induces syncytia in a variety of embryonic bovine tissues in vitro. Antigenic analyses have demonstrated a conservation of epitopes between the major core protein of BIV and HIV. The original isolate has been molecularly cloned and sequenced. Besides the three large open reading frames (ORFs) comprising the gag, pol, and env genes common to all replication-competent retroviruses, five additional small ORFs were found. Numerous point mutations and deletions were found, mostly in the env-encoding ORF. These data suggest that, within a single virus isolate, BIV displays extensive genomic variation.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Effect of nutritional rehabilitation on circulating ghrelin and growth hormone levels in patients with anorexia nervosa.

Circulating ghrelin and growth hormone (GH) are up-regulated in anorexia nervosa (AN) as a consequence of prolonged starvation. The current study examines the effect of nutritional rehabilitation with improvement of eating behavior on ghrelin and GH levels in AN patients during the course of inpatient treatment. The subjects included 34 female AN patients and 9 age-matched female controls. Fasting blood samples were collected before, during and after treatment. For data analysis, AN subjects were divided into three subtypes. The first group included seven patients with emergent hospitalization (E-AN), who were accompanied by severe emaciation due to their inability for food intake for more than a month. The other two groups included 14 AN with restricting (AN-R) and 13 AN with binge-eating/purging (AN-BP) patients. There were significant correlations between ghrelin, GH and body mass index (BMI) before treatment in all subjects. However, ghrelin levels were not significantly correlated with BMI and GH although there was a relationship between GH and BMI after treatment. Before treatment, E-AN patients had the highest levels of ghrelin and GH with the lowest glucose levels and liver dysfunction. The AN-BP group had a higher level of ghrelin than the AN-R group. During treatment, comparing with the controls group only the AN-R group showed higher level of ghrelin. Contrarily, the ghrelin levels in the E-AN group, who showed improved glucose levels, and the AN-BP group, who stopped vomiting behavior due to our treatment, decreased ghrelin levels. After treatment, only the AN-BP group showed a higher ghrelin level as compared to the controls. Although GH levels of the three AN groups decreased gradually according to our treatment progress, it still showed the higher value than the control group at the end of the treatment because every AN patients could not reach to more than 80% of their ideal body weight at discharge. These findings suggest that (1) severe emaciation with abnormal fasting hypoglycemia in AN patients may cause very high levels of GH and ghrelin, (2) that GH levels in AN patients may relate to nutritional status and (3) that ghrelin may be influenced by not only nutritional status but also the eating behavior of the patients.

Adult↗

The pathology of experimental Trypanosoma evansi infection in the Indonesian buffalo (Bubalus bubalis).

Six Indonesian buffaloes (Bubalus bubalis) were inoculated intravenously with 10(5) Trypanosoma evansi, examined clinically, haematologically and serologically, and then killed 1, 2, 3, 4, 8 or 12 weeks after infection for detailed pathological study. Relapsing fever was related to the waves of parasitaemia and fluctuations of pulse and respiration rates. Anaemic mucous membranes, depression, weakness, refusal to walk, loss of appetite and emaciation were seen. Body weight, packed cell volume, total platelet and red cell counts, and haemoglobin values were below those of two uninfected control buffaloes, as well as below the normal range; on the other hand antibody titres against T. evansi in infected animals were all above those in controls. Emaciation, serous atrophy of fat, hydropericardium, petechial to larger haemorrhages in the pericardium, pneumonia, congested liver and spleen, oedematous enlargement of the superficial lymph nodes and hyperplastic bone marrow were the major gross pathological changes. Histologically, the severity of the disease increased from 1 to 7 weeks after infection and became less obvious at 12 weeks. The most consistent lesions were interstitial pneumonia, interstitial myocarditis, splenic multifocal necrosis, interstitial myositis and hyperplastic bone marrow. The last three lesions appear not to have been reported previously in T. evansi infection in buffaloes or other animals. The clinicopathological findings in this study show that T. evansi is both an intravascular and extravascular parasite.

Animals↗

Influence of age, sex and body condition on zinc, copper, cadmium and metallothioneins in common guillemots (Uria aalge) stranded at the Belgian coast.

The common guillemots, Uria aalge, found stranded at the Belgian coast, display high levels of Cu in both liver and kidneys. The condition index of the animals, defined as the ratio of liver to kidneys mass (Wenzel & Adelung, 1996, The suitability of oiled Guillemots (Uria aalge) as monitoring organisms for geographical comparisons of trace element contaminants. Archives of Environmental Contamination and Toxicology, 31, 368-377), influences both the metal concentration and its binding to metallothioneins (MT): the lower the condition index, the more emaciated the animals, and the higher the total Cu concentration and the concentration of Cu bound to MT. In less robust individuals, our results suggest that Cu could displace Zn from MT, rendering the Zn ions available to induce a new MT synthesis. Sex-related effects also emerged as significantly higher hepatic MT as well as Cu- and Zn-MT concentrations were found in emaciated male guillemots compared to females. In both organs, Cd concentrations remained low and typically demonstrated an age-dependent renal accumulation, with no noticeable effect of the condition index. As a whole, these results suggest that, for guillemots found stranded at the Belgian coast. Cu binding to hepatic and renal MT could function as a protective mechanism, rendering the metal ions unavailable to exert any cytotoxic activity.

Age Factors↗

Pathogenicity for mice and swine of Erysipelothrix isolates from the tonsils of healthy cattle.

The pathogenicity of 79 Erysipelothrix isolates from bovine tonsils for mice and swine was determined. Five (6.3%) isolates were lethal for mice. These isolates belonged to serovars 1b (one isolate), 2 (2), 19 (1) and 21 (1). The 50% lethal dose values of the isolates ranged from 0.33 to 5x10(2) CFUs in mice. Twenty Erysipelothrix isolates (25.3%) were weakly virulent inducing only emaciation while 12 (15.2%) inducing emaciation and ruffled hair. In swine, clinical signs of varying severity were observed. Four isolates were virulent, capable of inducing localized or generalized urticarial lesions accompanied with a rise in body temperature after intradermal inoculation. One isolate each of serovars 1b, 2 and 19 was highly virulent, capable of inducing generalized urticarial lesions while another Erysipelothrix isolate of serovar 2 induced only a localized urticarial lesion at the site of inoculation. Another isolate of serovar 1b induced itching and irritation without obvious urticarial lesion at the site of inoculation. On the other hand, one isolate of serovar 21 and two other isolates of serovar 2 could not induce experimentally any clinical sign of erysipelas other than rise in body temperature. There was a rise in growth agglutination (GA) titer of serum in all the inoculated swine. These observations suggest that Erysipelothrix isolates from cattle are pathogenic for mouse and swine, and may also be pathogenic for other animals and humans.

Agglutination Tests↗

Investigations of the potential influence of environmental contaminants on the thymus and spleen of harbor porpoises (Phocoena phocoena).

Harbor porpoises from the German North and Baltic Seas exhibit a higher incidence of bacterial infections compared to whales from less polluted arctic waters. The potential adverse effect of environmental contaminants such as polychlorinated biphenyls (PCBs) and heavy metals on the immune system and the health status of marine mammals is still discussed controversially. The aim of the present study was to investigate the possible influence of PCB, polybrominated diphenyl ether (PBDE), toxaphene, (p,p'-dichlorodiphenyl)trichlorethane (DDT), and (p,p'-dichlorodiphenyl)dichlorethene (DDE) on the immune system of harbor porpoises. Lymphoid organs are influenced by a variety of factors, and therefore special emphasis was given to separating the confounding effect of age, health status, nutritional state, geographical location, and sex from the effect of contaminant levels upon thymus and spleen. Contaminant analysis and detailed pathological examinations were conducted on 61 by-caught and stranded whales from the North and Baltic Seas and Icelandic and Norwegian waters. Stranded harbor porpoises were more severely diseased than by-caught animals. Thymic atrophy and splenic depletion were significantly correlated to increased PCB and PBDE levels. However, lymphoid depletion was also associated with emaciation and an impaired health status. The present report supports the hypothesis of a contaminant-induced immunosuppression, possibly contributing to disease susceptibility in harbor porpoises. However, further studies are needed to determine if lymphoid depletion is primarily contaminant-induced or secondary to disease and emaciation in this cetacean species.

Animals↗

Schistosoma bovis in western Uganda.

During routine parasitological surveillance and monitoring activities within a National Control Programme for control of human schistosomiasis in Uganda, it was noted that cattle grazing in a water meadow immediately adjacent to Tonya primary school, where the prevalence of intestinal schistosomiasis in children was in excess of 90%, were unusually emaciated. To test the hypothesis that there may have been an anthropozoonotic focus of Schistosoma mansoni within the local herd, a young female heifer, clearly emaciated and c. 8 months old, was slaughtered from which schistosome worms were later recovered by dissection. As female worms inspected by microscopy were not gravid, morphological identification proved inconclusive but analysis of cytochrome oxidase subunit I (COI) and small subunit (SSU) ribosomal DNA sequences from these worms identified them as Schistosoma bovis Sonsino, 1876. This is the first substantiated report of S. bovis from Lake Albert, western Uganda. Further epidemiological surveys are needed to clarify the extent of bovine schistosomiasis within this region, particularly so since this lakeside plain has been earmarked as a future game reserve.

Animals↗

Heart risk associated with weight loss in anorexia nervosa and eating disorders: electrocardiographic changes during the early phase of refeeding.

Refeeding syndromes with electrolyte aberrations, heart failure and arrhythmias may complicate the nutritional rehabilitation of emaciated patients with eating disorders. Therefore, electrocardiographic (ECG) changes and changes in serum electrolyte concentrations following refeeding were studied in 37 admissions of 32 teenage girls with eating disorders. On admission they were all on a weight-losing course and weighed 37.0+/-8.0 kg (mean +/- SD) following a weight loss of 14.2+/-7.2 kg. On ECG recordings there was a prolongation of the QT interval and an increased QT dispersion. Serum concentrations of sodium, potassium and magnesium were with few exceptions normal. Serum concentrations of creatinine were high in relation to the low body weight, indicating protein catabolism. The first 2 wk of refeeding resulted in a weight gain of 1.7+/-0.2 kg without signs of refeeding syndromes or electrolyte aberrations. QT prolongation and dispersion normalized within the 3 d of refeeding. It is concluded that oral refeeding of patients with eating disorders and weight loss can be performed efficiently and without causing refeeding syndromes. QT pathology, a consequence of acute starvation and a risk factor for cardiac arrhythmias, normalizes within days. In view of the need to balance adequate refeeding and reduction of QT pathology against the risks of refeeding syndromes the start of refeeding of severely emaciated patients is best performed in a hospital setting where monitoring of ECG and serum electrolytes is possible.

Adolescent↗

Surgical syndromes of the hypothalamus.

The clinical syndromes described with lesions of the hypothalamus are summarized in Table 9.5-9.7. The anterior hypothalamic syndrome consists of insomnia and loss of thirst regulatory mechanisms. In occasional larger lesions which interrupt the output from the supraoptic and paraventricular nuclei, diabetes insipidus has been noticed. In the tuberal region of the hypothalamus the most prominent findings are those that are caused by the disruption of the final common pathway to the pituitary. This results in endocrinopathy, most often the syndrome originally reported by Frohlich, with failure of sexual maturation and obesity. In the tuberal region, differences between lesions of the medial and lateral portions are quite marked. Medial lesions result in obesity while bilateral lesions result in anorexia and emaciation. The diencephalic syndrome of infancy with it's severe emaciation in young years and obesity in later years clearly indicates a different organizational pattern in the neonatal hypothalamus. Emotional disorders may be seen with lesions either in the medial or lateral hypothalamus at the tuberal level. Finally, in the posterior hypothalamic region, which includes the greatest effector apparatus, hypersomnia, apathy, and poikilothermia have been reported. Emotional disturbances and the Wernicke-Korsakoff syndrome also seemed to be associated with lesions in this area. The hypothalamus remains the single most important integrator of vegetative and endocrinologic regulation of the body. Cushing said of the hypothalamus, "here in this hidden spot, almost to be covered with a thumb nail, lies the very main spring of primitive existence: vegetative, emotional and reproductive".

Adenoma↗

Adrenal activity in anorexia nervosa.

Adrenocortical activity was studied in 19 emaciated women with anorexia nervosa. Relative to body size the patients' mean cortisol production rates of 0.591 mg/kg/day and 16.4 mg m2/day were significantly elevated compared to those of 0.322 mg/kg/day and 11.4 mg/m2/day for age and sex matched normal controls (p less than 0.001 and 0.02, respectively). The 24-hr mean plasma cortisol concentration in 18 patients was 10.6 microgram/dl and was significantly higher than that of the controls (6.8 microgram/dl, p less than 0.001). The average excretion of urinary free cortisol in nine patients was 205 microgram/day, significantly greater than that of 65 microgram/day in the controls (less than 0.01). Three patients underwent overnight suppression with 1 mg of dexamethasone and had inadequate responses. These data suggest that cortisol production is excessive in emaciated patients with anorexia nervosa due to a disturbance of the hypothalamic-pituitary mechanisms regulating adrenocortical function. The excessive adrenal activity may reflect certain psychobiological disturbances as well as the effects of malnutrition.

Adolescent↗

Effects of rapamycin in experimental organ allografting.

The immunosuppressive effect of rapamycin (RAPA), a macrolide antibiotic produced by Streptomyces hygroscopicus, was tested using allografts in the rat and dog. It was immunosuppressive at a dose of 3.0 mg/kg/day for 8 days in skin allografts and 0.1 mg/kg/day for 11 days using cardiac allografts in the rat. It prevented rejection of renal allografts in beagle dogs at a dose of 0.3 mg/kg; however, emaciation and gastrointestinal toxicity resulted in some deaths in dogs. Mucosal necrosis and vasculitis in the submucosal layer were the predominant findings at autopsy in dogs receiving RAPA. Serum amylase values rose soon after commencement of RAPA treatment. Combined drug treatment with CsA at a nonimmunosuppressive dose of 3.2 mg/kg in the rat or 2.5 mg/kg in the dog was synergistic, with a low dose of 0.1 mg/kg/week RAPA. Combined therapy of CsA and RAPA also inhibited the frequency of vasculitis and emaciation in dogs. The present data suggest that RAPA is immunosuppressive in organ allografting and that the combination of CsA and RAPA would be effective clinically.

Animals↗

Unexpected death in patients suffering from eating disorders. A medico-legal study.

Medico-legal investigation into causes of unexpected death of five persons who suffered from eating disorders did not give distinct pathoanatomical explanations. The analysis disclosed a number of risk factors whose interplay may have resulted in a circulatory catastrophy. These factors were of organisational and ideological character: simultaneous treatment at different departments, lack of contact with psychiatrists, or unclear criteria for admission to hospital; or somatic: circulatory and electrocardiographic S-T and T wave abnormalities, hypopotassemia and hypoglycemia, as well as anergy of the emaciated patient which may have led to symptoms of bronchopneumonia being overlooked. Morphological investigation revealed heart atrophy as well as recent lesions such as haemorrhages, fragmentation and contraction bands of the myofibres. In two extremely emaciated patients there was a disproportion between the size of the mitral valves and the atrophic ventricular wall, an appearance similar to "floppy valves". In one instance an erroneously inserted gastric tube contributed to vomiting, hypopotassemia and sudden death.

Adolescent↗

Pathological investigations on guillemots (Uria aalge) stranded on the Belgian coast during the winter of 1993-94.

Pathological investigations were carried out on 67 guillemots (Uria aalge) washed up on the Belgian coast between November 1993 and March 1994. Emaciation and acute haemorrhagic gastroenteropathy were observed in more than 70 per cent of the birds. There was no statistical relationship between the level of oil contamination and the severity of the lesions. Differences in bodyweight were accounted for by age, sex, emaciation, and acute haemorrhagic gastroenteropathy. The birds had a severe weight deficit but the concentrations of pollutants were below acutely toxic levels.

Animals↗

Comparison of estrogen priming effects with body weight restoration effects on the gonadotropin pattern of patients with anorexia nervosa.

Plasma estradiol (E2), serum LH and FSH, and the gonadotropin response to two consecutive LHRH administrations (10 and 100 micrograms with an interval of 2 h) were determined in 19 patients with anorexia nervosa (AN) at the emaciation phase, before and after estradiol benzoate (E2B) injections (3 micrograms/kg/day for 7 days). The same investigations were repeated after weight restoration in 9 AN patients who remained amenorrheic. Both at the emaciation phase and after weight restoration, E2B enhanced the second LH response to LHRH and decreased serum FSH, suggesting that the functional capacities of the pituitary gonadotrophs are normal in AN. Unlike E2B injections, weight restoration increased all the hormone values, suggesting that the weight restoration effects on the abnormal gonadotropin secretory pattern of AN depend on another mechanism than the E2 lowering. That mechanism is probably a disorder of the hypothalamic LHRH secretion, the consequences of which could be reinforced by the low E2 levels.

Adolescent↗

Visceral mycosis in Chinook salmon (Oncorhynchus tschawytscha) due to Sporobolomyces salmonicolor.

One-month-old Chinook salmon fry from a cold-water hatchery were presented live for euthanasia and necropsy. Gross lesions were emaciation in 90% of the fry and ascites and increased cutaneous pigmentation in the remaining 10%. A cause for the emaciation was not determined. Histologically, the fry with ascites and increased pigmentation had visceral mycosis with aerocystitis, myositis, peritonitis, and dermatitis. Sporobolomyces salmonicolor, a rare human pathogen, was isolated and identified in tissue sections from affected fry.

Animals↗

Experimentally induced selenosis of adult mallard ducks: clinical signs, lesions, and toxicology.

Selenosis is thought to be a significant problem among waterfowl populations in selenium-contaminated wetlands in the western United States. Chemical analysis of avian tissues is currently the principal basis for diagnosis. The purpose of these two 150-day studies was to establish whether morphological criteria for selenosis could be developed to supplement chemical analysis. Forty-eight flightling male mallard ducks were fed either a proprietary waterfowl ration (< 1 ppm selenium) or the same ration amended to contain 10, 25, and 60 ppm selenium supplied as seleno-L-methionine (n = 12/group). In a separate study, 12 birds fed twice daily were offered either a proprietary ration or a selenium-supplemented ration (120 microg/g) for one of two daily feedings. Selenium in whole blood increased from baseline concentrations (< 0.4 microg/ml) to means of 4.5, 8.9, and 16.0 microg/ml in the 10-, 25-, and 60-ppm groups, respectively. All birds in the 60-ppm-dose group rapidly lost weight and were killed (11/12) or died (1/12) between 22 and 50 days of dietary exposure. In addition to emaciation, six of 12 birds (50%) fed the 60-microg/g diet developed mild to moderate generalized hepatopathy with single-cell necrosis, karyomegaly of hepatocytes, hyperplastic bile duct epithelium, and/or iron accumulation in Kupffer cells. The principal lesions in birds exposed to other dietary concentrations of selenium involved integumentary structures containing hard keratin. Gross lesions developed after 76 days of dietary exposure and consisted of bilaterally symmetrical alopecia of the scalp and dorsal cervical midline, broken or lost digital nails, and necrosis of the tip of the beak (maxillary nail). One or more of these three lesions were present in 0/12 birds (0%) fed 10 ppm selenium, 5/12 birds (42%) fed 25 ppm selenium, and 4/9 (44%) birds fed a split-feed diet containing 120 ppm selenium. Controls were unaffected. Histologic lesions in digital and maxillary nails consisted of single-cell to full-thickness necrosis of keratinocytes and multifocal parakeratosis in stratum corneum. Histologic lesions in alopecic skin (necrosis of the epidermal collar, inflammation of the feather pulp, and follicular keratosis) were mild. Some birds with alopecia had no detectable lesions in feather follicles from affected areas of skin. The highest tissue concentrations of selenium were in liver, kidney, and feathers, respectively. Mean hepatic tissue concentrations were 14.5 microg/g (10 ppm group), 29.6 microg/g (25 ppm group), 60.6 microg/g (60 ppm group), 13.0 microg/g (120 ppm split-feed group), and 2.0 microg/g (controls). Integumentary and hepatic lesions may be of value in corroborating a diagnosis of selenosis based on chemical analysis of tissues from naturally intoxicated waterfowl. Some birds with fatal selenosis may have no morphologic lesions other than emaciation.

Alopecia↗