Whither recombinant human growth hormone?
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HIV Wasting Syndrome↗
Biomedical subjects
C S Mantzoros
Publications and source records attributed to C S Mantzoros.
Zinc status and serum testosterone levels of healthy adults.
Zinc deficiency is prevalent throughout the world, including the USA. Severe and moderate deficiency of zinc is associated with hypogonadism in men. However, the effect of marginal zinc deficiency on serum testosterone concentration is not known. We studied the relationship between cellular zinc concentrations and serum testosterone cross-sectionally in 40 normal men, 20 to 80 y of age. In four normal young men (27.5 +/- 0.5 y), we measured serum testosterone before and during marginal zinc deficiency induced by restricting dietary zinc intake. We also measured serum testosterone in nine elderly men (64 +/- 9 y) who were marginally zinc deficient before and after 3 to 6 mo of supplementation with 459 mumol/ d oral zinc administered as zinc gluconate. Serum testosterone concentrations were significantly correlated with cellular zinc concentrations in the cross-sectional study (lymphocyte zinc versus serum testosterone, r = 0.43, p = 0.006; granulocyte zinc versus serum testosterone, r = 0.30, p = 0.03). Dietary zinc restriction in normal young men was associated with a significant decrease in serum testosterone concentrations after 20 weeks of zinc restriction (baseline versus post-zinc restriction mean +/- SD, 39.9 +/- 7.1 versus 10.6 +/- 3.6 nmol/L, respectively; p = 0.005). Zinc supplementation of marginally zinc-deficient normal elderly men for six months resulted in an increase in serum testosterone from 8.3 +/- 6.3 to 16.0 +/- 4.4 nmol/L (p = 0.02). We conclude that zinc may play an important role in modulating serum testosterone levels in normal men.
Adult↗
Conicity index as a predictor of blood pressure levels, insulin and triglyceride concentrations of healthy premenopausal women.
Conicity index (C index), an index of abdominal obesity that was developed based on a model of geometric reasoning, proved to be a sensitive and better than the waist to hip ratio indicator of risk for hyperlipidemia in Western populations. To evaluate comparatively the C index and the Waist-to-Hip Ratio (WHR) as predictors of blood pressure levels, insulin and triglyceride concentrations, we performed a cross-sectional study on 280 healthy women, 18-24 year-old. C index was found to be within the expected range (0.95 to 1.73) and significantly correlated with WHR (r = 0.562, p = 0.0001) and body weight (r = 0.312, p = 0.0001). Additionally, C index correlated with fasting insulin levels (r = 0.13, p = 0.03), and systolic blood pressure (r = 0.14, p = 0.02). WHR correlated with fasting insulin levels (r = 0.12, p = 0.05), systolic blood pressure (r = 0.12, p = 0.13) and triglycerides (r = 0.22, p = 0.0006). C index and WHR are equally good, albeit weak, predictors of fasting insulin and blood pressure levels, while WHR proved to be a better than C index predictor of triglyceride concentrations in this population of healthy premenopausal Greek women. Further epidemiologic studies to comparatively evaluate the two indexes as predictors of risk for the development of metabolic disorders and cardiovascular disease in various populations are needed.
Adolescent↗
Evidence for leptin binding to proteins in serum of rodents and humans: modulation with obesity.
Many hormones circulate bound to serum proteins that modulate ligand bioactivity and bioavailability. To understand the biology of leptin action, we investigated the presence of leptin binding proteins in serum. 125I-labeled leptin binds competitively to at least three serum macromolecules with molecular masses of approximately 85, approximately 176, and approximately 240 kDa in rodents and approximately 176 and approximately 240 kDa in humans. The ability to bind appears to involve sulfhydryl/disulfide interactions because it is inhibited under reducing conditions. When serum is added to recombinant 125I-leptin, there is a shift in sedimentation of 125I-leptin as analyzed by sucrose gradient centrifugation from approximately S1.9 to approximately S4.3. This shift is markedly attenuated in serum from obese mice (ob/ob, db/db, brown-fat ablated, gold-thioglucose treated, high-fat fed) compared with that from nonobese controls. The size distribution of endogenous serum leptin as determined by radioimmunoassay (RIA) after sucrose gradient centrifugation is also consistent with saturation of binding in hyperleptinemic obesity. In humans, free leptin increases with BMI. Thus, in lean rodents and humans a large proportion of leptin circulates bound to several serum proteins. Free leptin is increased in serum of obese subjects, which may alter leptin bioactivity, transport, and/or clearance.
Adult↗
Activation of beta(3) adrenergic receptors suppresses leptin expression and mediates a leptin-independent inhibition of food intake in mice.
To examine potential interactions between leptin and the beta3 adrenergic system in the regulation of food intake, we determined the effects of treatment with a selective beta3 adrenergic receptor (AR) agonist (CL 316,243 [1 mg/kg]) on body weight, food intake, and leptin expression. Studies were carried out in C57Bl/6J and FVB male control mice as well as in mice with targeted disruption of the beta3 AR gene. These findings were correlated with measurement of the expression in hypothalamus of neuropeptide Y (NPY) and melanin concentrating hormone (MCH), two neuropeptides that may be involved in the central regulation of food intake. Treatment with CL 316,243 (1 mg/kg) for 12 or 24 h decreased leptin mRNA abundance and circulating levels to 20% of baseline in normal animals. No effect of the CL 316,243 compound was seen in mice with targeted disruption of the beta3 AR gene. Despite the failing leptin levels, beta3 agonist administration acutely suppressed food intake. Finally, the induced suppression of food intake and leptin levels occurred despite unchanged or increased hypothalamic expression of the orexigenic neuropeptides NPY and MCH. Thus, beta3 AR agonists via beta3 ARs suppress leptin levels acutely and simultaneously suppress food intake via a mechanism that operates downstream of leptin and two of its putative central targets.
Adipose Tissue↗
Dehydroepiandrosterone sulfate and testosterone are independently associated with body fat distribution in premenopausal women.
To evaluate the relative importance of androgen and insulin concentrations in predicting body fat distribution, we measured their association with waist-hip ratio in a sample of 151 consecutively enrolled healthy premenopausal women age 18-24 years, after controlling for potential confounding variables. Dehydroepiandrosterone sulfate (DHEAS) and total testosterone were independently associated with waist-hip ratio, whereas insulin and free testosterone did not appear to play a role of comparable importance. Differences in concentrations of circulating DHEAS and total testosterone are independently associated with the waist-hip ratio in premenopausal women, providing epidemiologic support to the "neuroendocrine dysregulation" hypothesis for the pathogenesis of central obesity.
Adipose Tissue↗
Contribution of dihydrotestosterone to male sexual behaviour.
OBJECTIVE: To document the relative importance of endogenous sex steroids in modulating the frequency of orgasms, the dominant aspect of sexual behaviour in healthy eugonadal men. DESIGN: Measurement of adrenal and testicular sex steroids in a sample of army recruits and study of their relation to frequency of orgasms ascertained by questionnaire after potential confounding variables were controlled for. SETTING: Military campus and military hospital laboratories in Athens, Greece. SUBJECTS: 92 consecutively enrolled healthy male recruits aged 18-22 years. MAIN OUTCOME MEASURES: Weekly number of orgasms. Serum concentrations of testosterone, dehydroepiandrosterone sulphate, dihydrotestosterone, oestradiol, oestrone, delta-4-androstenedione, and sex hormone binding globulin. RESULTS: Serum dihydrotestosterone concentration was the only independent hormonal predictor of the frequency of orgasms; an increase in concentration of 1.36 nmol/l (about 2 SD) corresponded to an average increase of one orgasm a week. CONCLUSIONS: Differences in concentrations of circulating dihydrotestosterone within the normal range may represent a major predictor of sexual activity in healthy young men.
Adult↗
Relative androgenicity, blood pressure levels, and cardiovascular risk factors in young healthy women.
To test the hypothesis that androgens may play a role in the pathogenesis of atherosclerosis and hypertension, we investigated the association of delta 5 dehydroepiandrosterone sulfate [DHEAS]) and delta 4 (free testosterone [FT]) androgens with the resting, seated blood pressure (BP) levels and cardiovascular risk factors in 280 young, healthy women 18 to 24 years of age. After application of multiple regression analysis, systolic BP was positively and independently correlated with the ratio of dehydroepiandrosterone sulfate to free testosterone (DHEAS/FT), fasting insulin levels, and the diastolic BP with DHEAS/FT only. The DHEAS/FT ratio proved to be a stronger predictor of the BP levels than either hormone alone. Further, uric acid concentrations and HDL/total cholesterol ratio were independently correlated with both FT and body mass index in these young women. Serum triglycerides were independently correlated with FT and central body fat distribution. These data suggest that serum androgen concentrations are important independent predictors of cardiovascular risk factors and that the ratio of dehydroepiandrosterone sulfate to free testosterone ratio is an independent predictor of blood pressure levels in young women.
Acetone↗
Outcome of percutaneous transluminal coronary angioplasty in patients with subclinical hypothyroidism.
To determine the outcomes of percutaneous transluminal angioplasty (PTCA) in patients with subclinical hypothyroidism and to compare them with those in euthyroid patients, we studied retrospectively 48 hypothyroid (4 overtly and 44 subclinically hypothyroid) and 122 euthyroid patients who had a PTCA in Boston's Beth Israel Hospital between 1984 and 1994. No significant differences were detected in bradycardia (relative risk, RR: 0.96), tachyarrhythmia (RR: 0.62), heart failure (RR: 2.27), hypotension (RR: 1.95), or bleeding (RR: 2.48) in the immediate postprocedure period between euthyroid and subclinically hypothyroid patients. There was a trend towards an increased incidence of chest pain (43.2 vs 27.5%, RR: 1.57, p = 0.084), dissection (50 vs 33%, RR: 1.51, p = 0.06) as an immediate, and reocclusion as an early (within 2 weeks) postprocedure complication (6.25 vs .9%, RR: 6.81, p = 0.08). However, chest pain accompanied by electrocardiographic changes was not significantly different between the two groups (20.5 vs 14.7%, RR: 1.4, p = 0.47). There was no difference in the number of procedures rated as successful (subclinically hypothyroid vs euthyroid: 90.2 vs 92.7%). Hospital charges, discharge destination, interval to next admission to the hospital, and in-hospital mortality were not different between the two groups. Subclinical hypothyroidism does not appear to be a risk factor for significant morbidity or increased mortality following PTCA. Prospective long-term studies with increased statistical power are needed to clarify whether there is an association between hypothyroidism and complications (especially chest pain, dissection, and/or reocclussion) in the early (2 weeks) and late (6 months) post-PTCA period.
Aged↗
Body mass and physical activity are important predictors of serum androgen concentrations in young healthy men.
The relative importance of body mass index (BMI), demographic, and life-style factors in predicting androgen and sex hormone-binding globulin (SHBG) concentrations of young healthy men has not been clearly established. We evaluated the role of age, BMI, height, habitual physical activity, education, smoking, coffee and alcohol intake as predictors of serum testosterone, dihydrotestosterone, dehydroepiandrosterone sulfate, androstenedione, and SHBG concentrations in 100 healthy men 18-22 years old. BMI was the only independent predictor of dihydrotestosterone and dehydroepiandrosterone sulfate, and both BMI and physical activity were independent predictors of serum testosterone concentrations, whereas other variables did not appear to play a role of comparable importance.
Adolescent↗
Isolated combined growth hormone and gonadotrophin deficiency due to hypothalamic dysfunction, associated with insulin resistance.
A 47-year-old woman was evaluated for congenital dwarfism, primary amenorrhoea due to hypogonadotrophic hypogonadism, severe hyperlipidaemia with pancreatitis, and overt diabetes mellitus associated with severe insulin resistance requiring 2.5-3 units of insulin per kilogram body weight. Chromosomal analysis with trypsin banding was normal and biochemical evaluation revealed low oestrogen levels, inappropriately low gonadotrophins, very low IGF-I concentrations and GH concentrations unresponsive to insulin or L-dopa administration. Prolactin, pituitary-adrenal and pituitary-thyroid axes were normal. Dynamic testing with GnRH and GHRH produced increases in FSH, LH and GH concentrations. A MRI of the brain revealed no discernible hypothalamic abnormalities and a small pituitary. The presence of congenital combined growth hormone and gonadotrophin deficiency on the basis of a suprapituitary defect suggests the existence of common or related pathways regulating GnRH and GHRH synthesis or secretion and may have contributed to the ultimate development of insulin resistance and hyperlipidaemia.
Adult↗
Imaging of the sella in the syndrome of inappropriate secretion of antidiuretic hormone.
OBJECTIVE: The syndrome of inappropriate secretion of antidiuretic hormone (SIADH) results either from ectopic production or inappropriate release of antidiuretic hormone from the neurohypophysis. Although magnetic resonance imaging (MRI) has provided new insights into the morphological changes of the hypophysis in health and disease, no previous studies have evaluated its use in SIADH: The aim of this study was to evaluate the MRI appearance of the neurohypophysis in patients with SIADH: DESIGN: Retrospective case-control study. SETTING: Tertiary care teaching hospital. SUBJECTS: We studied retrospectively eight patients with SIADH who had been hospitalized in Boston's Beth Israel between 1984 and 1994 and who had MRI scans including the sella turcica. We also evaluated prospectively the MRIs of the heads of 23 consecutive control patients who had no pituitary pathology and no serum osmolality or electrolyte abnormalities. INTERVENTIONS: Clinical evaluation as well as sagittal and axial T1-MR images. MAIN OUTCOME MEASURES: Presence or absence of the high intensity signal of the neurohypophysis. RESULTS: In seven out of eight patients (87.5%) the normal high intensity signal of the neurohypophysis was not present. In one patient (12.5%), two interpreting radiologists disagreed about its presence. The high intensity signal was present in the neurohypophysis of 20 out of 23 controls (87.5%). CONCLUSIONS: Our data indicate an association of SIADH with the absence of the normal hyperintense signal of the neurohypophysis, confirming the usefulness of MRI as a tool to visualize ADH processing. These data also raise the possibility that the absence of the high intensity signal may be useful diagnostic tool in cases of SIADH that are difficult to diagnose clinically. Additional studies to correlate this signal with various forms of SIADH will be needed.
Adult↗
Insulin resistance in a patient with ovarian stromal hyperthecosis and the hyperandrogenism, insulin resistance and acanthosis nigricans syndrome. Report of a case with a possible endogenous ovarian factor.
Insulin resistance is a common feature of ovarian stromal hyperthecosis and is usually accompanied by hyperandrogenemia. A patient had ovarian stromal hyperthecosis, and her hyperandrogenemia resolved, possibly due to the development of a type of ovarian fibrosis similar to so-called ovarian fibromatosis, without a concomitant improvement in her insulin resistance. The insulin resistance improved markedly, however, after bilateral oophorectomy.
Acanthosis Nigricans↗
Insulin resistance: the clinical spectrum.
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Arteriosclerosis↗
In vitro relaxation of phenylephrine- and angiotensin II-contracted aortic rings by beta-estradiol.
In vivo studies suggest that 17 beta-estradiol (beta E) may regulate vascular tone. Results of recent studies suggest that beta E exerts rapid effects on intracellular calcium, possibly via cell surface receptors, distinct from conventional nuclear receptors for steroids. The present study was designed to determine whether beta E acutely modifies vascular smooth muscle contractile responses to phenylephrine (PE) and angiotensin II (AII). In experiments on tonic responses of aortic rings to 5 x 10(-8) mol/L PE, cumulative additions of beta E reduced tension at concentrations > 10(-6) mol/L. Contractile dose responses to PE were determined in rat aortic rings in absence of sex hormones and then after exposure to beta E (5 x 10(-6) mol/L, n = 6) or vehicle (ETOH, n = 6) for 30 min. beta E increased ED50 and reduced maximal responses. Application of 5 x 10(-6) mol/L beta E for 30 min also reduced the contractile response to 1 mmol/L AII from 69 +/- 4% (vehicle) to 47 +/- 6% (estradiol) of maximal KCl contraction (P < .025, n = 7). These data suggest that beta E acutely attenuates vasoconstrictor responses to PE as well as to AII, possibly by an effect exerted at the cell membrane level.
Angiotensin II↗
Paralytic ileus as a result of diltiazem treatment.
Diltiazem is a widely used calcium channel blocker, and has been found to be effective in the treatment of hypertension, stable, variant and unstable angina, as well as oesophageal spasm. Calcium channel antagonists have been shown to diminish the contractility of gut smooth muscle, but have not as yet been reported to cause clinically significant inhibition of gut motility when used alone. We report a case of reversible functional intestinal obstruction, immediately following diltiazem treatment in a patient with ischaemic heart disease.
Aged↗
Treatment of myxedema-associated cardiogenic shock.
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Humans↗
Extraosseous epidural tuberculoma: case report and review.
Extraosseous epidural tuberculoma has been reported infrequently, in spite of the widespread availability in recent years of computerized axial tomography and magnetic resonance imaging that can detect bony involvement not apparent on roentgenography with plain films. Thirty-two cases of extraosseous epidural tuberculoma have been reported in the English-language literature; however, only seven of these were radiologically and microbiologically confirmed. The single case from North America was reported over 30 years ago. We describe a patient with a spinal epidural mass due to Mycobacterium tuberculosis that was not associated with bony involvement and review the epidemiology, pathophysiology, presentation, and outcome of the previously reported cases.
Adult↗