Amenorrhoea in Anorexia Nervosa: Assessment and Treatment with Clomiphene Citrate

Seven patients with anorexia nervosa were studied, three during the acute stages of the illness, and four in whom weight gain had been achieved, but who suffered from persistent amenorrhoea of 18 to 79 months'' duration.In the acute stage all patients had low serum luteinizing hormone (LH) levels which were unresponsive to clomiphene citrate. In those who had regained weight the mean basal LH levels were normal, and they responded to clomiphene with an initial doubling of serum LH during administration of the drug, followed by a second peak of serum LH four to seven days after the drug was stopped. Menstruation occurred in these patients 13 to 19 days after the clomiphene was discontinued, and in two patients regular spontaneous menstruation was initiated.The low LH levels unresponsive to clomiphene in the acute stage provide evidence for a hypothalamic abnormality in anorexia nervosa. After regain of body weight the drug seems to be effective in treating the amenorrhoea which may be persistent.     

Balloon catheter dilatation and thrombectomy for acute aortoiliac occlusion

A case of acute distal aortic thrombosis in an elderly high-risk patient was successfully managed with intraoperative thrombectomy and balloon catheter dilatation of the common iliac arteries. Balloon catheter dilatation may be indicated prior to bypass grafting in high-risk patients with acute aortoiliac thrombosis.     

Resting tachycardia, a warning sign in anorexia nervosa: case report

Background

Among psychiatric disorders, anorexia nervosa has the highest mortality rate. During an exacerbation of this illness, patients frequently present with nonspecific symptoms. Upon hospitalization, anorexia nervosa patients are often markedly bradycardic, which may be an adaptive response to progressive weight loss and negative energy balance. When anorexia nervosa patients manifest tachycardia, even heart rates in the 80–90 bpm range, a supervening acute illness should be suspected.

Case presentation

A 52-year old woman with longstanding anorexia nervosa was hospitalized due to progressive leg pain, weakness, and fatigue accompanied by marked weight loss. On physical examination she was cachectic but in no apparent distress. She had fine lanugo-type hair over her face and arms with an erythematous rash noted on her palms and left lower extremity. Her blood pressure was 96/50 mm Hg and resting heart rate was 106 bpm though she appeared euvolemic. Laboratory tests revealed anemia, mild leukocytosis, and hypoalbuminemia. She was initially treated with enteral feedings for an exacerbation of anorexia nervosa, but increasing leukocytosis without fever and worsening left leg pain prompted the diagnosis of an indolent left lower extremity cellulitis. With antibiotic therapy her heart rate decreased to 45 bpm despite minimal restoration of body weight.

Conclusions

Bradycardia is a characteristic feature of anorexia nervosa particularly with significant weight loss. When anorexia nervosa patients present with nonspecific symptoms, resting tachycardia should prompt a search for potentially life-threatening conditions.     

Evaluation of Diagnostic Significance of Certain Symptoms and Physical Signs in Anaemic Patients

In a study of 133 anaemic and 111 non-anaemic hospital patients pallor of recent onset was the only symptom which was significantly associated with the severity of the anaemia. Dizziness in acute blood loss anaemia, and anorexia and painful tongue in vitamin-B₁₂ deficiency, were the only symptoms which might be helpful in diagnosing the type of anaemia. The frequency of glossitis in patients with megaloblastosis was confirmed, but neither glossitis nor nail changes were significantly more common in patients with iron-deficiency anaemia than in the control patients.     

Clinically apparent eating disorders in young diabetic women: associations with painful neuropathy and other complications.

Of 208 young women with insulin dependent diabetes, 15 (7%) had a clinically apparent eating disorder (anorexia nervosa or bulimia), a much higher prevalence than reported in non-diabetic women. Most, but not all, of these patients had a long history of poor glycaemic control. In contrast with previous suggestions, control did not deteriorate after the onset of the eating disorder. There was a high incidence and an early onset of diabetic complications. Eleven of the 15 patients had retinopathy, six with proliferative changes; six had nephropathy; and six neuropathy. Most strikingly, four patients with anorexia nervosa developed acute painful polyneuropathy. In each case pain started when the eating disorder developed, almost coinciding with the peak of weight reduction. Remission of pain occurred as weight was regained. The symptoms were accompanied by abnormalities in peripheral nerve electrophysiology and autonomic nerve function, some improvements in which accompanied weight recovery. It is suggested that nutritional factors may contribute to the high rate of early onset diabetic complications, particularly neuropathy.     

Human pancreatic polypeptide responsiveness to insulin-induced hypoglycemia in anorexia nervosa

Patients with anorexia nervosa occasionally suffer from hypoglycemic comas. We investigated the role of human pancreatic polypeptide (HPP) in insulin-induced hypoglycemia (0.1 U/kg of regular insulin). Ten female patients with anorexia nervosa (20.7 +/- 2.0 years, mean +/- SEM; 34.9 +/- 1.7 kg, mean +/- SEM) and 8 age-matched female controls (20.9 +/- 0.6 years, 51.5 +/- 0.8 kg) were tested. In the patients with anorexia nervosa, testing was performed before and after the restoration of body weight (45.0 +/- 0.8 kg). There was no significant difference in glucose nadir between patients with anorexia nervosa and the control subjects. However, glucose recovery from nadir was delayed in patients with anorexia nervosa. In anorexia nervosa patients, the plasma pancreatic glucagon responses to insulin-induced hypoglycemia did not differ from those of the controls. Results also showed, however, that HPP responses to insulin-induced hypoglycemia were significantly higher in patients with anorexia nervosa than in controls (p less than 0.01). The increased HPP responses were still present after the restoration of body weight in anorexia nervosa patients. A complete body weight recovery or a longer period of time may be required to normalize the HPP response to insulin-induced hypoglycemia in patients with anorexia nervosa, after the restoration of body weight.     

Leptin role in advanced lung cancer. A mediator of the acute phase response or a marker of the status of nutrition?

Leptin is an anorexia inductor peptide produced by adipocytes and related to fat mass. Leptin is also produced by fat under proinflammatory cytokine action. Our objective is to study serum leptin levels in relation to nutritional status and acute phase response in advanced-stage non-small cell lung cancer.Seventy-six patients newly diagnosed of non surgical non-small cell lung cancer before chemotherapy treatment and 30 healthy controls were included. BMI, serum leptin and cholesterol levels and lymphocyte count were decreased in lung cancer patients. Cytokine IL-6, TNF-alpha, sTNF-RII, sIL-2R, IL-12, IL-10 and IFN-gamma, and other acute phase reactants as alpha1 antitrypsin, ferritin, CRP and platelets were all raised in patients, whereas the IL-2 was decreased. We found a direct relationship between leptin and other indicators of the status of nutrition, especially total fat mass. We also found a close relationship between the status of nutrition and the performance status (Karnofsky index). However, serum leptin and nutritional status were inversely correlated with acute phase proteins and proinflammatory cytokines, suggesting a stress-type malnutrition. Although serum leptin levels, nutritional status and Karnofsky index are related to survival, at multivariate analysis they all were displaced by the acute phase reaction markers.These results suggest that cancer anorexia and cachexia are not due to a dysregulation of leptin production. Circulating leptin concentrations are not elevated in weight-losing cancer patients and are inversely related to the intensity of the inflammatory response. In advanced lung cancer patients serum leptin concentrations only depend on the total amount of fat.     

COX-2-dependent delayed dilatation of cerebral arterioles in response to bradykinin

Bradykinin (BK) is released in the brain during injury and inflammation. Activation of endothelial BK receptors produces acute dilatation of cerebral arterioles that is mediated by reactive oxygen species (ROS). ROS can also modulate gene expression, including expression of the inducible isoform of cyclooxygenase (COX-2). We hypothesized that exposure of the brain to BK would produce acute dilatation, which would be followed by a delayed dilatation mediated by COX-2. To test this hypothesis in anesthetized rats, BK was placed twice in cranial windows for 7 min, after which the windows were flushed to remove residual BK. The two BK exposures were separated by 30 min. Each BK exposure produced acute dilatation of cerebral arterioles, after which diameter rapidly returned to baseline. Over the subsequent 4.5 h after the second BK exposure, arterioles dilated 48 +/- 8%. Treatment of the cranial window with NS-398, a selective COX-2 inhibitor, or dexamethasone, significantly attenuated the delayed dilatation. Aminoguanidine, a selective inhibitor of inducible nitric oxide synthase, did not alter the delayed dilatation. Cotreatment of cranial windows with BK, superoxide dismutase, and catalase also prevented the delayed dilatation. In separate experiments, exposure of the cortical surface to BK upregulated leptomeningeal expression of COX-2 mRNA. Our results suggest that acute, time-limited exposure of the brain to BK produces delayed dilatation of cerebral arterioles dependent on expression and activity of COX-2.     

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)     

Gastrin levels and gastric emptying times in rhesus monkeys with a history of acute gastric dilatation

Abstract: Abnormal gastric motility has been suggested as a possible causative factor for acute gastric dilatation observed in nonhuman primates. To evaluate gastric motility in a colony, fasting serum gastrin immunoreactivity and gastric emptying times were assessed in rhesus monkeys that had survived single episodes of acute gastric dilatation. These were paired with age- and weight-matched control monkeys from the same colony. Neither gastric emptying times nor gastrin assays were significantly different between the acute gastric dilatation and control groups.     

The gonadotropin releasing hormone stimulation and the clomiphene tests in female patients with anorexia nervosa.

In 9 female patients suffering from acute anorexia nervosa (a.n.) and in two patients in whom this disease had reached the remission phase, the response of the gonadotropin-producing cells in the adenohypophysis was checked by administration of Gn-RH and the degree to which the hypothalamic-hypophyseal axis could be stimulated was checked by administration of clomiphene (5 x 100 mg). Hormonal screening examinations (cervical score after Insler and hormonal vaginal cytology) were used to assay the basal estrogen production. LH and FSH concentrations in the serum were determined radioimmunologically using the principles of the double antibody technique. The gonadotropin-producing cells did not respond to Gn-RH administration in 8 of the 9 patients with acute a.n. The response was disturbed in one of these patients. The response to Gn-RH stimulation was normal in the two patients in the remission phase. Clomiphene had no stimulatory effect on the hypothalamic-hypophyseal axis during either the acute or remission phase. Hormonal treatment during the acute phase of a.n. is not indicated since, after recovery of a normal body weight, the symptoms recede and the cycle normalises spontaneously.     

Cholecystokinin-induced hypophagia is not potentiated by cancer anorexia

The interaction of cholecystokinin-induced hypophagia with cancer anorexia was investigated within both acute (Walker 256 carcinosarcoma) and chronic (methylcholanthrene-induced sarcoma) animal models of cancer anorexia. Cholecystokinin octapeptide (CCK8) effectively reduced feeding for at least one hour in both groups of rats. However, this peptide was no more effective in inducing hypophagia in tumor-bearing rats than in nontumor-bearing control rats when tested at a variety of doses (0.5, 5.0 and 50.0 microgram/kg; IP) both prior to and after the development of anorexia. Therefore, these data do not support a role of cholecystokinin in the mediation of experimental cancer anorexia, since no synergism of CCK8-induced hypophagia with the anorexia was observed.     

Role for nerve growth factor in the in vivo regulation of glutathione in response to LPS in mice

Since the redox state regulator glutathione (GSH), which influences lipopolysaccharide (LPS) anorexia, may be controlled by cytokines, we studied the roles of tumour necrosis factor-alpha (TNFalpha) and nerve growth factor (NGF) in the GSH response to intraperitoneal (ip) LPS injection in mice. Basal NGF and total reduced GSH (trGSH) levels were up-regulated in brain and liver of TNFalpha-knock-out (KO) mice, and this was associated with attenuated LPS anorexia. The increases in NGF and trGSH presumably contributed to the attenuated anorexia in response to LPS because transgenic mice over-expressing NGF (NGF-tg mice) also had increased trGSH levels and displayed attenuated anorexia compared to the corresponding wild type (WT) mice. Attenuated LPS anorexia in NGF-tg mice was accompanied by reduced serum TNFalpha and IFNgamma levels compared to WT mice. In response to a second injection of LPS, NGF and trGSH levels, but not TNFalpha levels changed. This suggests that in vivo tissue trGSH changes following LPS in LPS-na?ve or LPS-pretreated mice are regulated by NGF rather than TNFalpha. The finding that genetic TNFalpha deficiency did not inhibit the acute trGSH response to LPS supports this interpretation. In sum, the results indicate i) that a decrease or increase in NGF is accompanied by a decrease or increase in trGSH levels and ii) that elevated NGF and/or trGSH levels attenuate some of the responses to LPS such as anorexia and cytokine production.     

Observations on acute gastric dilatation in nonhuman primates.

In the years 1967-1977 we diagnosed 23 cases of acute gastric dilatation in monkeys. Fourteen of these animals were Macaca mulatta, five Macaca fascicularis, and one each of Macaca nemestrina, Aotus trivirgatus, Saimiri sciureus, and Colobus guereza. Fourteen of the animals were males, nine were females, and all were adults or subadults. Mortality was 78% (18 of 23 animals). Thirteen of the animals had received on anesthetic, immobilizing, or tranquilizing drug 1-2 days before developing acute gastric dilatation; seven monkeys were overfed, and two had been transferred from one area to another the day prior to developing the disease. Two animals were found dead in their cages with no apparent cause for the gastric dilatation. Five Macaca mulatta and three Macaca fascicularis recovered following treatment, but two Macaca mulatta subsequently succumbed to another episode of acute gastric dilatation. Treatment consisted of evacuation of the stomach, correction of blood volume deficits and acid-base disturbances by administration of appropriate fluids, and supportive therapy for shock.     

Toxic Dilatation of the Colon in the Course of Ulcerative Colitis

Toxic dilatation of the colon has been observed in a patient suffering from ulcerative colitis during an acute relapse of the disease. This uncommon and serious complication was suspected because there was a gradual worsening of the patient''s condition, accompanied by toxic phenomena. The diagnosis was confirmed by a flat plate of the abdomen which disclosed considerable dilatation of the colon. The etiology of toxic dilatation is not known but the use of opiates and anticholinergic agents has been suggested as a possible factor. These therapeutic agents should be avoided in the acute stage. Barium enema examination during acute relapses of ulcerative colitis may also precipitate the onset of this complication. It is recommended that, during the acute stage of the disease, the barium enema be replaced as often as possible by flat films of the abdomen which also enable diagnosis of this complication.     

Serum leptin levels in patients with anorexia nervosa before and after partial refeeding, relationships to serum lipids and biochemical nutritional parameters.

Leptin is a protein hormone produced by adipocytes that provide information about the body fat content. It was previously reported that serum leptin levels were decreased in patients with anorexia nervosa in comparison with healthy control subjects. The aim of our study was to compare serum leptin levels in patients with anorexia nervosa (n=11, initial mean BMI=15.4 kg/m2) before and after partial recovery with control age-matched subjects (n=11, mean BMI= 20.3 kg/m2) and to study the relationships of leptin levels, serum lipids and biochemical nutritional parameters. We found that serum leptin concentrations in patients with anorexia nervosa were significantly reduced in comparison with control subjects (3.61 vs 9.37 ng.ml(-1), p<0.01). Serum cholesterol, triglycerides, total protein and albumin in patients with anorexia nervosa either before or after partial recovery did not differ from the control group. After partial recovery, a significant increase in serum leptin was observed (4.83 vs 3.61 ng.ml(-1), p<0.05), but the values still remained significantly lower than in the control group (p<0.01) Leptin levels correlated positively with the body mass index in the control group and anorexia nervosa group before recovery. The correlation with BMI in the anorexia nervosa group after refeeding was not significant. No significant correlation was found between leptin concentrations and serum lipids, total protein, albumin and prealbumin, respectively. Serum leptin thus represents a sensitive parameter that reflects the nutritional status in patients with anorexia nervosa suitable for long-term follow up during refeeding therapy.     

Nutrición basada en la evidencia en la pancreatitis aguda y la enfermedad hepática crónica estable

Acute pancreatitis is a disease that, by definition, generates an increase in metabolism. This metabolic reaction, together with the anorexia produced by the disease, clearly increases morbidity and mortality secondary to malnutrition.Malnutrition affects almost 70% of patients with cirrhosis, with a consequent increase in complications. The present review aims to evaluate the utility of the use of total parenteral nutrition (TPN) and/or enteral nutrition (EN) in patients with acute pancreatitis and in those with stable chronic liver disease.In patients with acute pancreatitis, the administration of enteral nutrition seems to confer advantages over parenteral nutrition in clinical variables (infections, surgical interventions, and mean length of hospital stay) (A-B); nevertheless, further studies stratifying patients according to the severity of pancreatitis and probably its etiology should be designed. Glutamine supplementation can be effective in reducing length of hospital stay and duration of nutritional support (B).In patients with stable chronic liver disease, there are no studies that demonstrate the superiority of EN over PN, or vice versa, in relevant clinical variables (mortality, length of hospital stay, etc.). There is only one study that has demonstrated that EN is superior to oral intake in reducing mortality (B).Improved study designs and the need to perform studies according to the type and severity of liver disease should be a research priority.     

Cancer Incidence among Patients with Anorexia Nervosa from Sweden,Denmark and Finland

A diet with restricted energy content reduces the occurrence of cancer in animal experiments. It is not known if the underlying mechanism also exists in human beings. To determine whether cancer incidence is reduced among patients with anorexia nervosa who tend to have a low intake of energy, we carried out a retrospective cohort study of 22 654 women and 1678 men diagnosed with anorexia nervosa at ages 10-50 years during 1968-2010 according to National Hospital Registers in Sweden, Denmark and Finland. The comparison group consisted of randomly selected persons from population registers who were similar to the anorexia nervosa patients in respect to sex, year of birth and place of residence. Patients and population comparisons were followed for cancer by linkage to Cancer Registries. Incidence rate ratios (IRR) were estimated using Poisson models. In total, 366 cases of cancer (excluding non-melanoma skin cancer) were seen among women with anorexia nervosa, and the IRR for all cancer sites was 0.97 (95% CI = 0.87-1.08) adjusted for age, parity and age at first child. There were 76 breast cancers corresponding to an adjusted IRR of 0.61 (95% CI = 0.49-0.77). Significantly increased IRRs were observed for esophageal, lung, and liver cancer. Among men with anorexia nervosa, there were 23 cases of cancer (age-adjusted IRR = 1.08; 95% CI = 0.71-1.66). There seems to be no general reduction in cancer occurrence among patients with anorexia nervosa, giving little support to the energy restriction hypothesis.     

Immediate and long-term outcomes of the use of a Crossflex wire coronary stent in the treatment of patients with different forms of ischemic heart disease

Immediate and medium-term prognoses were studied in patients with coronary heart disease in whom a Crossflex wire coronary stent (Cordis, Johnson & Johnson, USA) had been inserted into the coronary arteries. The study indicated that it could be effectively used in patients with both chronic coronary heart disease and its exacerbation (acute myocardial infarction). It was found that in the vast majority of patients anginal attacks ceased and the clinical course ran smoothly in both immediate and medium-term postoperative periods. In the immediate period, various complications were observed only in 6.7% of cases. In the late period, the incidence of restenosis was 24%. If restenosis occurred, repeated balloon dilatation was successfully made in the great majority of cases by resulting in recovery of the vascular lumen.     

Hypothalamic pituitary adrenal function in patients with anorexia nervosa.

Hypothalamic pituitary adrenal function was studied in 14 patients with anorexia nervosa. Although basal plasma cortisol levels in the morning were elevated in most cases, basal plasma ACTH levels were not suppressed. Oral administration of 1 mg dexamethasone 10 hr before blood sampling failed to suppress plasma ACTH and cortisol levels in most patients with anorexia nervosa. Apparent biological half-life of exogenous cortisol was prolonged in all 4 patients with anorexia nervosa tested. The cortisol response to insulin-induced hypoglycemia and exogenous ACTH appeared to be blunted in these patients. It is concluded that anorexia nervosa has dysfunctions of hypothalamic pituitary adrenal axis, especially an abnormal feedback mechanism on ACTH secretion.