Cardiovascular findings in adolescent inpatients with anorexia nervosa

Left ventricular function, resting electrocardiograms, and Holter recordings were systematically examined in 25 consecutively hospitalized, seriously ill, emaciated adolescents with anorexia nervosa. We failed to observe serious arrhythmias, abnormal prolongation of QT interval, conduction abnormalities, or depression in left ventricular systolic function.     

Magnetic resonance spectroscopic and relaxometric determination of bone marrow changes in anorexia nervosa

OBJECTIVE: The objective of this study was to assess and quantify bone marrow changes in patients with anorexia nervosa using 1H magnetic resonance spectroscopy and relaxometry. METHODS: The bone marrow fat fraction and the longitudinal and transverse relaxation times (T1 and T2, respectively) of water were measured in the lumbar and femoral marrow of 20 patients with anorexia nervosa and 19 healthy control subjects. RESULTS: Patients with anorexia nervosa showed significant hyperhydration and reduction of the fat fraction in their bone marrow, predominantly in the proximal femur. These changes were associated with hematological abnormalities. In a retest of seven patients after psychotherapy and gain of weight, the pathological changes in marrow proved to be largely reversible in correlation with the increase in body mass index. CONCLUSIONS: Fat depletion and excess of tissue water in the bone marrow in anorexia nervosa can be quantified by 1H magnetic resonance spectroscopy and relaxometry. The distribution of the pathological changes in the lumbar and femoral marrow follows the pattern of normal bone marrow conversion from hematopoietic to cellular during childhood.     

Structural brain changes in patients with anorexia nervosa

Twenty-five patients with anorexia nervosa were compared with 17 normal healthy control subjects in terms of their cerebral computed tomographic (CT) scan appearances. The patients displayed significantly greater ventricular and sulcal enlargement when compared to control subjects. There were no relationships between the CT scan appearance and clinical indices of illness severity or weight loss in the patient group. In 14 patients who had repeat scans after attaining normal body weight, no significant change was observed in the ventricular appearance, but there was a significant lessening in the degree of sulcal widening.     

Hyperinsulinemia; a mediator of decreased food intake and weight loss in anorexia nervosa and major depression

Decreased food intake and weight loss are seen in eating and depressive disorders. No satisfactory pathophysiological mechanisms have been proposed to explain those findings. While it should be kept in mind that the etiology of those diseases is still unclear, it seems reasonable to propose that the maintenance of anorectic behavior in the eating disorders as well as the decreased food intake of major depression, leading to continued weight loss seen in both conditions, are either caused or mediated by insulin in levels which are elevated but insufficient to cause hypoglycemia. A brief review is made of the role of insulin in satiety and in the control of body weight, and of the newly available techniques to accurately quantify secretion, hepatic extraction, and post-hepatic delivery rates of insulin. Neural, metabolic, and endocrine stimuli affect insulin secretion. The hypothesis is therefore compatible with several etiologic factors leading to hyperinsulinemia in anorexia nervosa and major depression, and resulting in decreased food intake and weight loss.     

Bone marrow findings correlate with clinical outcome in systemic AL amyloidosis patients

AIMS: Bone marrow sampling is a key investigation in the work-up of amyloid light chain (AL) amyloidosis, but the relationship between bone marrow findings and the varied phenotype and clinical outcome of AL amyloidosis is unclear. The aim was to determine if bone marrow pathological parameters at diagnosis were related to clinical behaviour in AL amyloidosis patients. METHODS AND RESULTS: Bone marrow findings, clinical features and outcome of 80 patients referred with a diagnosis of systemic AL amyloidosis were evaluated; six patients were subsequently excluded due to re-categorization as other forms of amyloidosis. At latest follow-up (median 66 months), 11 of the 18 patients with no identifiable bone marrow neoplastic cells (61%) versus only seven of the 56 patients with neoplastic plasma cells or non-Hodgkin's lymphoma (13%) were alive (P = 0.0046). However, neither the quantity of the neoplastic cells nor the serum light chain levels were correlated with amyloid burden or patient survival. CONCLUSIONS: Identification of a neoplastic population in the bone marrow of AL amyloidosis patients by histology and immunohistochemistry correlates with poor outcome; however, the neoplastic cell burden is not prognostically significant, suggesting that additional factors are important in determining disease behaviour in AL amyloidosis.     

A histochemical study of bone marrow hypoplasia in anorexia nervosa

Summary The bone marrow in patients with anorexia nervosa is commonly hypoplastic with transformation of marrow fat. The normal fat cells which appear clear and open in the marrow are surrounded by an amorphous, gelatinous material, thought to represent an increase in the ordinary acid mucopolysaccharide ground substance of the bone marrow. Since this lesion has a similar appearance grossly and microscopically to the lesion of serous fat atrophy found in cachectic patients, we have compared the histochemical properties of this amorphous material in a bone marrow from a patient with anorexia nervosa and from cachectic patients with epicardial serous fat atrophy and with the background substance in hypoplastic marrows. Both this fat-associated deposition in the bone marrow and serous fat atrophy were found to be predominantly a hyaluronic acid mucopolysaccharide. In contrast, the background substance contained a less acid mucopolysaccharide. The increase in bone marrow acid mucopolysaccharide in anorexia nervosa may represent a serous fat atrophy change rather than an increase in ground substance.     

Diminished creatinine clearance in anorexia nervosa: reversal with weight gain.

To assess whether patients with anorexia nervosa have abnormalities in creatinine clearance, we measured plasma creatinine concentration, urinary creatinine excretion, and creatinine clearance in 10 patients with anorexia nervosa before and during treatment. Urinary creatinine excretion and creatinine clearance were diminished in all patients. Nine patients had significant decreases in their plasma creatinine and creatinine clearance was increased even when corrected for body weight and body surface area respectively. The patient who did not show these changes in plasma creatinine concentration and creatinine clearance had gained only 4% in body weight. Body weight and corrected creatinine clearance were significantly correlated, as were percentage increases in body weight and creatinine clearance. Thus anorexia nervosa is associated with a reversible decrease in creatinine clearance. Increase in body weight appears to be cardinal to the recovery of renal function in these patients.     

Radiographic findings in osteoarthritis of the knee joint are not correlated with cartilage histomorphology or immunohistochemistry

The purpose of this study was to investigate whether radiographic joint space narrowing (JSN) of the lateral knee compartment predicts the histomorphological or immunhistochemical grading in cases of osteoarthritis of the knee joint. The lateral joint space was measured on weight-bearing radiographs. Femoral osteochondral plugs of 29 patients undergoing total knee replacement were obtained from lateral condyles. All these patients had severe osteoarthritis of the medial compartment, with the lateral compartment showing different stages of osteoarthritis. The specimens were histomorphologically evaluated with the Mankin score, and the expression of the cartilage-degrading enzymes MMP1 and MMP3 was measured. There was no correlation between the joint space and histomorphological or immunohistochemical data, whereas the enzyme expression was correlated with histomorphological grading. We conclude that radiographic assessment alone is not sufficient to evaluate the cartilage damage of the lateral condyle.     

Plasma levels of neuroactive steroids are increased in untreated women with anorexia nervosa or bulimia nervosa

OBJECTIVE: Animal data suggest that neuroactive steroids, such as 3alpha,5alpha-tetrahydroprogesterone (3a,5a-THP), dehydroepiandrosterone (DHEA), and its sulfated metabolite (DHEA-S), are involved in the modulation of eating behavior, aggressiveness, mood, and anxiety. Anorexia nervosa (AN) and bulimia nervosa (BN) are eating disorders characterized by abnormal eating patterns, depressive and anxious symptoms, enhanced aggressiveness, and endocrine alterations. Previous studies reported decreased blood levels of DHEA and DHEA-S in small samples of anorexic patients, whereas no study has been performed to evaluate the secretion of these neuroactive steroids in BN as well as the production of 3alpha,5alpha-THP in both AN and BN. Therefore, we measured plasma levels of DHEA, DHEA-S, 3alpha,5alpha-THP and other hormones in patients with AN or BN and explored possible relationships between neuroactive steroids and psychopathology. METHOD: Ninety-two women participated in the study. There were 30 drug-free AN patients, 32 drug-free BN patients, and 30 age-matched, healthy control subjects. Blood samples were collected in the morning for determination of hormone levels. Eating-related psychopathology, depressive symptoms, and aggressiveness were rated by using specific psychopathological scales. RESULTS: Compared with healthy women, both AN and BN patients exhibited increased plasma levels of 3alpha,5alpha-THP, DHEA, DHEA-S, and cortisol but reduced concentrations of 17beta-estradiol. Plasma testosterone levels were decreased in anorexic women but not in bulimic women. Plasma levels of neuroactive steroids were not correlated with any clinical or demographic variable. CONCLUSIONS: These findings demonstrate increased morning plasma levels of peripheral neuroactive steroids in anorexic and bulimic patients. The relevance of such hormonal alterations to the pathophysiology of eating disorders remains to be elucidated.     

Intellect,perceptual characteristics,and weight gain in anorexia nervosa

Studied weight gain in a group of primary anorexics by examining two popular psychodiagnostic measures, the Wechsler and Rorschach, for indices that may predict improvement. Twenty-seven successively admitted anorexics to a behavior modification weight gain program at NIMH were studied. Using weight gain as a continuous criterion, multiple regression analyses indicated that perceptual-personality variables did not have any predictive power. Cognitive focusing skills, as measured by the Arithmetic and Digit Span subtests of the Wechsler, were found to account for roughly half of the variance and to be good predictors of weight gain.     

Bone marrow findings in lupus patients with pancytopenia

The marrow findings of 23 lupus patients with pancytopenia were reported. The most common findings were dyserythropoiesis and hypoplasia, both occurring in 9/23 (39%) of the cases. Neither feature was definitely related to cytotoxic drug therapy since most cases were treated by steroids only. Three of the hypoplastic marrows also showed gelatinous transformation, a condition characterized by disruption of marrow architecture, fat atrophy, and deposition of hyaluronic acid. Another common finding was lymphocytosis which occurred in 5/23 (22%) of the cases, 2 of which also had associated plasmacytosis. Two cases were associated with hyperplastic marrow, indicating peripheral destruction of blood cells and compensatory marrow hyperplasia. Reports in the literature on bone marrows in systemic lupus erythematosus are conflicting, describing mainly hypoplasia, vasculitis, plasmacytosis, red cell aplasia, and myelofibrosis. In our series, we found hypoplasia and lymphocytosis/plasmacytosis; in addition we described findings previously unreported: gelatinous transformation, dyserythropoiesis, and marrow hyperplasia.     

Capacity to produce cytokines during weight restoration in patients with anorexia nervosa.

OBJECTIVE: Anorexic patients are surprisingly free of infectious complications despite their seriously undernourished state. To study this phenomenon, we longitudinally measured the capacity to produce cytokines in restricting-type anorexic patients. METHODS: Lymphoproliferative responses with phytohemagglutinin (PHA) and the capacity of whole blood to produce cytokines, such as interleukin-1 (IL-1), IL-6, tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), and granulocyte-colony stimulating factor (G-CSF), were longitudinally measured before and after weight gain, that is, at admission and at less than 60, 65, and 75% of standard body weight (SBW), in 17 patients with restricting-type anorexia nervosa and in 17 control subjects. RESULTS: Cytokine production of IL-1, IL-6, and TNF-alpha per monocyte in the anorexic patients recovered only with the start of refeeding, whereas IFN-gamma production per lymphocyte was similar to that in control subjects and did not change during weight restoration. Only G-CSF production, even at 75% SBW, did not improve during weight restoration. Between the weight at admission and 65% SBW, the increase in the percentage of SBW and improvement of the total protein level were significantly correlated with improvement of the lymphocyte proliferative response with PHA. CONCLUSIONS: The capacity to produce most cytokines recovered with the start of weight gain; however, recovery was not correlated with weight gain. The results suggest that the capacity to produce cytokines in these anorexic patients was dependent on something other than the absolute value of body weight, such as the start of refeeding, the neuroendocrine system, or the autonomic nervous system.     

Dieting changes serotonergic function in women, not men: implications for the aetiology of anorexia nervosa?

The increase in plasma prolactin which follows intravenous administration of L-tryptophan (LTP) was used to assess changes in brain 5-hydroxytryptamine (5-HT) function in normal male and female subjects, following a three week period of dieting. In women, but not men, there was a marked increase in the prolactin response to LTP, suggesting that dieting had caused alterations in brain 5-HT-mediated responses. In contrast, dieting did not alter the prolactin response to thyrotropin releasing hormone in either men or women, indicating that the changes in response to LTP could not be attributed to an increase in pituitary reserve of prolactin. These findings suggest that dieting alters brain 5-HT function in women but not in men. Biological factors as well as greater psychosocial pressures to diet may contribute to the high prevalence of eating disorders amongst women.     

Bone marrow progenitors are not the source of expanding oval cells in injured liver

Liver progenitor/oval cells differentiate into hepatocytes and biliary epithelial cells, repopulating the liver when the regenerative capacity of hepatocytes is impaired. Recent studies have shown that hematopoietic bone marrow (BM) stem/progenitor cells can give rise to hepatocytes in diseased/damaged liver. One study has reported that BM cells can transdifferentiate into liver progenitor/oval cells, but it has not been proven that the latter can repopulate the liver. To answer this question, we have lethally irradiated female DPP4(-) mutant F344 rats and transplanted them with 50 million wild-type male F344 BM cells. One month after transplantation, the recipient BM was reconstituted with male hematopoietic cells, determined by quantitative polymerase chain reaction using primers for Y chromosome-specific sry gene. In addition, DPP4(+) cells, single or in clusters and predominantly in the periportal region, were detected in all liver sections of recipient rats. Animals were subjected to the following three different liver injury protocols for activation and expansion of oval cells: D-galactosamine, retrorsine/partial hepatectomy (Rs/PH), and 2-acetylaminofluorene/partial hepatectomy (2-AAF/PH). In all three models, prominent expansion and accumulation of cytokeratin 19-positive (CK-19(+)) oval cells was observed. However, most of the DPP4(+) clusters dispersed over time, and their total number decreased. Very few oval cells (less than 1%) showed double DPP4/CK-19 labeling. None of the small hepatocytic clusters in the Rs/PH or 2-AAF/PH model were comprised of DPP4(+) cells. These data demonstrate that the sources of oval cells and small hepatocytes in the injured liver are endogenous liver progenitors and that they do not arise through transdifferentiation from BM cells.