No abstract

In anorexia nervosa, serum GH levels are increased under basal conditions and respond abnormally to provocative stimuli. We report here, for the first time, an analysis of pulsatile GH secretion in these patients performed by Cluster algorithm. Seven anorectic and six normal weight, healthy women underwent serial blood sampling at 20-min intervals form 2030-0830 h for GH estimation. The total area under the curve (AUC; micrograms per L/min) was elevated 4-fold in anorectic patients compared to controls (4743.0 +/- 1520.09 vs. 1148.6 +/- 519.27; P < 0.01), largely due to an increase in the non-pulsatile fraction (3212.5 +/- 990.45 vs. 378.7 +/- 123.27; P < 0.01). Accordingly, the valley mean value was higher in anorectic than in control subjects (5.9 +/- 2.25 vs. 1.0 +/- 1.30 micrograms/L; P < 0.01). Furthermore, pulsatile AUC was also greater in anorectic patients (1530.4 +/- 654.72 vs. 769.8 +/- 404.02; P < 0.01) due to a significant increase in GH peak frequency (5.0 +/- 0.81 vs. 3.0 +/- 0.89; P < 0.01). No correlations were observed in these patients between body mass index and any of the parameters of spontaneous GH release, whereas a positive correlation was found between insulin-like growth factor I levels and pulsatile AUC (r2 = 0.583; P < 0.05), peak height (r2 = 0.743; P = 0.01), peak increment (r2 = 0.801; P < 0.01), and GH valley mean (r2 = 0.576; P < 0.05). In conclusion, it appears that the enhanced GH secretion in anorexia nervosa is the result of an increased frequency of secretory pulses superimposed on enhanced tonic GH secretion. Although this latter is consistent with a reduction of hypothalamic SRIH tone, the former may be accounted for by an increased number of GHRH discharges. Considering that in normal weight and obese subjects parameters of GH release are negatively correlated with adiposity indexes, the lack of such a negative correlation in our patients suggests that the enhancement of spontaneous GH release in anorectic patients is not merely the consequence of malnutrition-dependent impairment of insulin-like growth factor I production, but reflects a more complex hypothalamic dysregulation of GH release.

This study concerns 9 iv drug abusers with acquired immunodeficiency syndrome (AIDS) who developed hypercortisolism without the clinical signs or metabolic consequences of hypercortisolism. All patients were characterized by an Addisonian picture (weakness, weight loss, hypotension, hyponatremia, and intense mucocutaneous melanosis). An acquired form of peripheral resistance to glucocorticoids was suspected. We, therefore, examined glucocorticoid receptor characteristics on mononuclear leukocytes by measuring [3H]dexamethasone binding and the effect of dexamethasone on [3H]thymidine incorporation, which is one of the effects of glucocorticoid receptor activation. Glucocorticoid receptor density was increased in AIDS patients with an Addisonian picture (group 1; 16.2 +/- 9.4 fmol/million cells) compared to values in 12 AIDS patients without an Addisonian picture (group 2; 6.05 +/- 2.6 fmol/million cells; P less than 0.01) and sex- and age-matched controls (3.15 +/- 2.3 fmol/million cells; P less than 0.01). The affinity of glucocorticoid receptors (Kd) was strikingly decreased (9.36 +/- 3.44 nM in group 1; 3.2 +/- 1.5 nM in group 2; 2.0 +/- 0.8 nM in controls; P less than 0.01). [3H]Thymidine incorporation was decreased dose-dependently by dexamethasone in controls and patients; the effect was significantly blunted (P less than 0.05) in group 1 patients, which suggests that activation of glucocorticoid receptor is impaired as a result of the glucocorticoid receptor abnormality. In conclusion, AIDS patients with hypercortisolism and clinical features of peripheral resistance to glucocorticoids are characterized by abnormal glucocorticoid receptors on lymphocytes. Resistance to glucocorticoids implies a complex change in immune-endocrine function, which may be important in the course of immunodeficiency syndrome.

It is not clear whether brain natriuretic peptide (BNP) or N-terminal proBNP (NT-proBNP) is superior as a diagnostic and prognostic indicator in cardiac diseases. Here, we compare the clinical correlations of both peptides in a population of 92 ambulatory patients with heart failure, using a well-established immunoradiometric assay (IRMA) for BNP and an automated electrochemiluminescence immunoassay for NT-proBNP. The analytical correlation between the two peptides was satisfactory over a wide range of concentrations (1-686 pM for BNP) with the equation: NT-proBNP = 3.48 x BNP -19 and a correlation coefficient r2=0.94. In addition, the concentration of both peptides increased in a similar fashion according to the severity of the disease New York Heart Association (NYHA) functional class, left ventricular ejection fraction, etiology) and age; for instance, the ratios between median levels measured in NYHA class III vs. class II patients were comparable for BNP (383 vs. 16 pM, ratio 24) and NT-proBNP (1306 vs. 57 pM, ratio 23). We conclude that N-terminal proBNP, as assayed in the present study, correlates equally to BNP with clinical variables in patients with heart failure.

Discontinuous density sucrose gradient centrifugation was used to isolate membrane vesicles from the left ventricle of three normal subjects (one prospective organ donor and two traffic victims whose hearts were obtained 1 hour after death) and nine patients undergoing cardiac transplantation as a consequence of idiopathic dilated cardiomyopathy. Sarcolemma-enriched subcellular fractions, detected in the interface between 8.55% and 25% sucrose, were identified by the increased activity of Na+,K+-ATPase and by enrichment in beta-adrenergic receptor density. The density of beta-adrenergic receptors was lower in vesicles from diseased hearts (610 +/- 71 fmol/mg protein) than in vesicles from normal hearts (1,410 +/- 226 fmol/mg protein; p less than 0.01). alpha 1-Adrenergic receptors were identified in these membrane vesicles by [3H]prazosin binding. Specific binding of [3H]prazosin was about 50% of the total binding at 1 nM, and alpha 1-adrenergic binding sites were saturable at approximately 3 nM. Scatchard analysis revealed 58 +/- 5 fmol/mg protein (KD = 0.90 +/- 0.08 nM) in pathological hearts and 30 +/- 5 fmol/mg protein (KD = 0.90 +/- 0.03 nM) in normal hearts (p less than 0.01). The displacement curve of (-)-norepinephrine in membrane vesicles from normal hearts delineated one subpopulation of alpha 1-adrenergic receptors; the addition of 0.1 mM GTP did not cause right shift. In membrane vesicles from diseased heart, the displacement curve of (-)-norepinephrine disclosed two subpopulations of alpha 1-adrenergic receptors. A right shift that occurred after addition of GTP showed that in this case alpha 1-adrenergic receptors were functionally coupled with GTP-binding protein.(ABSTRACT TRUNCATED AT 250 WORDS)