Growth hormone improves body composition, fasting blood glucose, glucose tolerance and liver triacylglycerol in a mouse model of diet-induced obesity and type 2 diabetes.

AIMS/HYPOTHESIS: Growth hormone has been used experimentally in two studies to treat individuals with type 2 diabetes, with both reporting beneficial effects on glucose metabolism. However, concerns over potential diabetogenic actions of growth hormone complicate its anticipated use to treat type 2 diabetes. Thus, an animal model of type 2 diabetes could help evaluate the effects of growth hormone for treating this condition. METHODS: Male C57BL/6J mice were placed on a high-fat diet to induce obesity and type 2 diabetes. Starting at 16 weeks of age, mice were treated once daily for 6 weeks with one of four different doses of growth hormone. Body weight, body composition, fasting blood glucose, insulin, glucose tolerance, liver triacylglycerol, tissue weights and blood chemistries were determined. RESULTS: Body composition measurements revealed a dose-dependent decrease in fat and an increase in lean mass. Analysis of fat loss by depot revealed that subcutaneous and mesenteric fat was the most sensitive to growth hormone treatment. In addition, growth hormone treatment resulted in improvement in glucose metabolism, with the highest dose normalising glucose, glucose tolerance and liver triacylglycerol. In contrast, insulin levels were not altered by the treatment, nor did organ weights change. However, fasting plasma leptin and resistin were significantly decreased after growth hormone treatment. CONCLUSIONS/INTERPRETATION: Growth hormone therapy improves glucose metabolism in this mouse model of obesity and type 2 diabetes, providing a means to explore the molecular mechanism(s) of this treatment.

Decisions and ethical issues among BRCA carriers and the use of preimplantation genetic diagnosis.

The lifetime risks for both breast and ovarian cancer for BRCA mutation carriers far exceeds the general population risk of 13% for breast cancer and 1.4% for ovarian cancer. BRCA carriers have unique and medically complicated decisions to make regarding their cancer treatment or risk reduction. As BRCA testing becomes increasingly common among unaffected individuals in families with a previously documented BRCA mutation, there are a growing number of individuals with unique psychosocial needs and concerns. This review paper describes the BRCA 1/2 population, discusses preimplantation genetic diagnosis (PGD), and describes the decisions and ethical issues related to PGD among the BRCA 1/ 2 population.

Serum beta 2-microglobulin in the initial staging and subsequent monitoring of monoclonal plasma cell disorders.

Serum beta 2-microglobulin (beta 2-M) measurements were carried out in 97 patients with monoclonal plasma cell disorders. Twenty-six (87%) of 30 patients with monoclonal gammopathy of undetermined significance (MGUS) had increased beta 2-M levels and serial follow-up in seven patients showed a progressive increase with time. Of the 63 patients with active myeloma, pretreatment serum beta 2-M values were available in 25 for correlation with pretreatment stage. Stage III beta 2-M levels were significantly higher than stages I and II (p less than 0.001). Four patients with smoldering myeloma had beta 2-M values similar to stage I disease. There was, therefore, excellent correlation between beta 2-M and myeloma tumor burden. Levels of beta 2-M decreased with response to chemotherapy induction and low levels in stable remission (plateau phase) were associated with unusually good prognosis. Median survival for stage III patients in stable remission with low serum beta 2-M was greater than 48 months. Conversely, at relapse very high beta 2-M levels were associated with a very fulminant and refractory course. Serum beta 2-M, therefore, appears to be an extremely useful marker in initial stratification and follow-up of myeloma patients.

Neurogenic galactorrhea-amenorrhea.

Neuroendocrine function in two women with galactorrhea-amenorrhea arising from abnormalities in the PRL reflex arc was compared to that of normal women. Basal gonadotropins were lower than normal, and one patient lacked episodic secretion of LH; however, the serum gonadotropin rise after iv LRH was in the normal range in both patients. Mean basal PRL levels were slightly elevated in one patient and were normal in the other, and the PRL levels after TRH, chlorpromazine, and levodopa testing were similar to those seen in normal women. Breast stimulation did not increase PRL levels in either patient. PRL levels fell with bromergocryptine therapy, galactorrhea ceased, and normal menses resumed. These studies indicate that chronic afferent impulses originating in the PRL reflex arc can result in galactorrhea and amenorrhea and that bromergocryptine therapy in such patients can restore normal menses.

Hyperthyroidism with metastatic follicular thyroid carcinoma.

A 70-yr-old woman presented with hyperthyroidism and metastatic follicular carcinoma of the thyroid. The blood level of thyroid stimulating immunoglobulin (TSIg) was elevated. A total thyroidectomy was performed. One month later she remained hyperthyroid. Three weeks after therapy with 218 mCi of I-131 sodium iodide, the patient was euthyroid. Six months after the initial radioiodide therapy, she was again hyperthyroid and was given a second oral treatment dose of I-131 (220 mCi). Five months later, the patient had again become euthyroid. It is likely that initially the woman's metastases were producing sufficient hormone to render her hyperthyroid. After thyroidectomy and two large doses of radioiodide, she has remained euthyroid without having to take exogenous hormone. The blood level of TSIg had become undetectable. Based on this finding, we offer a tentative classification of the causes of hyperthyroidism in patients with thyroid carcinoma.

Oestrogen replacement therapy may improve memory functioning in the absence of APOE epsilon4.

There is currently intense controversy regarding the use of hormone replacement therapy (HRT) in postmenopausal women, in relation to its therapeutic efficacy in Alzheimer's disease (AD). It has been suggested that the benefits of HRT may be modified by apolipoprotein E (APOE) genotype (the major genetic risk factor for AD). Here we report the findings of the first study designed to systematically explore the interaction of (a) oestrogen replacement therapy (ERT) and (b) possession of an epsilon4 allele of APOE on specific elements of episodic learning and memory that are commonly used indices of age-related cognitive decline. This data represents a cross-sectional analysis of the interaction of ERT and APOE genotype on learning and memory in a cohort of 181 healthy postmenopausal women [ERT users (n = 101, mean age 65.40 +/- 6.34); ERT non-users (n = 80, mean age 67.03 +/- 6.80)] residing in Perth, Western Australia. The highest level of learning (trials 2-5; P < 0.05) and memory (e.g. total number of items recalled; P < 0.05) performance was observed in women taking ERT who were not carriers of the APOE epsilon4 allele. APOEepsilon4 carriers receiving ERT performed no better on episodic memory testing than APOE epsilon4 carriers who were not receiving ERT. These cognitive differences related to genetic profile, were noted on both recall and recognition (P = 0.005) tests of memory. The findings have significance for evaluating whether and when ERT may be clinically indicated. Specifically, ERT may benefit the cognitive functioning of women not carrying the APOE epsilon4 allele.

Fatal lipid storage myopathy in an infant: case report and autopsy findings.

The clinical presentation, muscle biopsy appearances and autopsy findings in a male infant dying at the age of 13 weeks with a lipid storage myopathy are described. The primary metabolic abnormality was not elucidated but was thought not to be carnitine deficiency.

Increased psychosocial stress and decreased mucosal immunity in children with recurrent upper respiratory tract infections.

The association between psychosocial stress and susceptibility to upper respiratory tract infection was investigated in 45 children with a history of recurrent colds and flu, and in 45 healthy children of similar age and distribution. In addition, mucosal immune protection against upper respiratory tract infections was assessed by measuring the concentration of secretory immunoglobulin A (sIgA) and its ratio to albumin in saliva. Several dimensions of psychosocial stress, including exposure to stressful experiences, stress-prone personality traits, and signs of emotional disturbance were elevated in children with a history of recurrent colds and flu. Furthermore, lower sIgA/albumin ratios in these children indicated a deficiency in local mucosal immunity. Thus, the findings are consistent with the view that psychosocial stress depletes local immune protection against viral invasion or bacterial colonization of the upper respiratory tract; this depletion may increase susceptibility to colds and flu. Alternatively, psychological disturbances could develop in response to frequent illness.

Psychological treatment for recurrent symptoms of colds and flu in children.

The effect of stress management and relaxation with guided imagery on upper respiratory tract infections (URTIs) was investigated in 45 children with a history of 10 or more infections in the past year. To investigate the influence of psychological treatment on mucosal immunity, secretory immunoglobulin A (sIgA) was measured before and during treatment. The number of symptomatic episodes during 13 weeks of monitoring was similar in treatment and waitlist conditions; however, episodes were shorter in stress management and guided imagery conditions than in the waitlist condition. Levels of sIgA increased toward the end of treatment. These findings were confirmed in a replication study. In addition, symptom reduction and improvements in psychological state persisted at 1-year follow-up. The findings suggest that psychological treatment interrupts a chronic illness cycle in children with symptoms of recurrent URTI.

Pure red cell aplasia and the syndrome of multiple endocrine gland insufficiency.

A 26-year-old female with the syndrome of multiple endocrine gland insufficiency developed pure red cell aplasia. A clinical remission of the pure red cell aplasia was induced with prednisone and cyclophosphamide therapy. The occurrence of these two disorders in a single patient allows speculation on a possible defect in immune surveillance leading to multisystemic immune dysfunction in this patient.

Secretory immunoglobulin A increases during relaxation in children with and without recurrent upper respiratory tract infections.

A diminished mucosal concentration of secretory immunoglobulin A (sIgA) in the upper respiratory tract may increase susceptibility to colds and flu. The aim of the present study was to determine whether sIgA increases during relaxation in children aged between 8 and 12 years with recurrent upper respiratory tract infections. Forty-five healthy children and 45 children with 10 or more upper respiratory tract infections in the previous year were randomly assigned to one of three experimental conditions: relaxation with suggestions to increase immune system proteins, relaxation alone, or a control condition. Samples of saliva were obtained before and after each condition. The concentration of sIgA in the saliva samples was later determined by measuring the rate of precipitation of antigen-antibody complexes to known concentration of sIgA antigen. The concentration of sIgA increased in the relaxation conditions but not in the control condition. The sIgA/albumin ratio (a more specific measure of local mucosal immunity than concentration) increased during the relaxation-suggestion condition but not during the relaxation or control conditions; however, both the concentration of sIgA and the sIgA/albumin ratio increased in proportion to subjective relaxation ratings. Neither response differed between healthy children and children with recurrent infections. The findings indicate that a disturbance in mucosal immunity in children with recurrent colds and flu does not limit increases in sIgA during relaxation. Higher preinfection levels of sIgA correlate with resistance to upper respiratory tract infection, so enhancing the sIgA concentration with relaxation techniques may help children with recurrent infection problems.

African American female basketball players: an examination of alcohol and drug behaviors.

The use of drugs and alcohol by National Collegiate Athletic Association Division I African American female basketball players and their reasons for using these substances were examined. The investigation is part of a broader study investigating the use of alcohol, weight-loss products, tobacco, amphetamines, and anabolic steroids by female college athletes. Of the 50 athletes in this study, 72% reported having consumed alcoholic beverages, and 46% had engaged in binge drinking. Only 8% reported using either weight-loss or tobacco products, and there were no reports of using amphetamines or anabolic steroids. Usage patterns indicated that the athletes in the study were aware of the short-term negative effects of alcohol and tobacco; those respondents who did use these products greatly reduced their consumption during the competitive season. Factors found to influence use include social and peer influences and coaches' rules.