The anterior pituitary response to a gonadotropin-releasing hormone challenge test in normal older reproductive-age women

OBJECTIVE: To assess the pituitary responsiveness to GnRH stimulation of premenopausal women relative to age. DESIGN: Older and younger reproductive-age women underwent the GnRH stimulation test in the early follicular phase of the menstrual cycle. SETTING: Female subjects in an academic research environment. PATIENTS: Women aged 21 to 44 years consisting of normal volunteers and infertility patients. INTERVENTIONS: Gonadotropin-releasing hormone was administered intravenously between days 2 and 4 of the menstrual cycle. Blood samples were collected from -20 minutes before to 120 minutes after administration. MAIN OUTCOME MEASURE: Luteinizing hormone, FSH, inhibin, and E2 levels. RESULTS: No significant difference in baseline values existed between older and younger women with regard to LH, inhibin, and E2, but basal FSH levels were higher in older women. A significantly diminished percent of LH and percent FSH change above baseline occurred 30 minutes after GnRH administration in the older women compared with younger women. No change in inhibin or E2 levels could be detected during the sampling period. CONCLUSIONS: The present study demonstrates marked attenuation of the acute pituitary LH response (sensitivity) to GnRH stimulation in older women when compared with a younger cohort.     

The combined corticotropin-releasing hormone/lysine vasopressin test discloses a corticotroph phenotype

The combined administration of CRH and vasopressin to man now offers a powerful means to directly assess the pituitary corticotroph reserve. A double blind, randomized, placebo-controlled, cross-over trial offered the opportunity to perform the combined CRH/lysine vasopressin (LVP) test (100 micrograms ovine CRH, followed by 1 IU LVP over 15 min) on 3 different occasions without treatment in 10 normal male subjects. We showed that peak ACTH plasma levels after stimulation had wide intersubject variation, whereas they were remarkably stable in a given individual, with a mean intraclass correlation coefficient of 0.90 (95% confidence limits, 0.74-0.96). Peak ACTH plasma levels after CRH/LVP administration were not significantly correlated with basal plasma cortisol levels (r = -0.14; P > 0.45), but were strongly and inversely correlated with peak cortisol plasma levels after Cortrosyn stimulation (0.25 mg, im; r = -0.78; P < 0.0001). These data provide the first evidence that the overall hypothalamic-pituitary-adrenocortical axis has an intrinsic activity that is constitutively fixed for a given individual. The power of the combined CRH/LVP test offers a unique means to measure a genuine corticotroph phenotype in each individual.     

Abnormal response of growth hormone to oral glucose tolerance test in obesity

In the first part of this paper we give a brief overview of the development of the different types of clinical assessment used in the UK. Some general problems related to the assessment of clinical practice are outlined. The second part of the paper focuses on the role of the external examiner in the clinical assessment of students. We outline some of the major problems we encountered as internal and external examiners on the same university-based course in which 'I-day' practical assessments were undertaken. We emphasize the particular problems of externally assessing the clinical practice component of the course in this manner and conclude that the continuous assessment model, while not without its own problems, is potentially a more effective approach to student assessment.     

Atrial natriuretic peptide in the subfornical organ reduces drinking induced by angiotensin or in response to water deprivation.

Three experiments tested whether the subfornical organ (SFO) could be a site of action for the antidipsogenic effects of atrial natriuretic peptide (ANP) in rats. Pretreatment with 100, 230, or 500 pmol ANP in the SFO reduced drinking induced by 10 pmol angiotensin II in the SFO. Drinking in response to water deprivation was reduced by ANP in rats having cannulas in or near the SFO, but not in rats having cannulas distant from the SFO or in the ventricles. Finally, ANP had no effect on eating or drinking after food deprivation, suggesting that the rats in the other experiments were not acutely incapacitated. The SFO may mediate the central effects of ANP on drinking induced by angiotensin or in response to water deprivation and could play a similar role in the central effects of ANP on salt appetite, diuresis, vasopressin secretion, and blood pressure. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Atrial natriuretic peptide inhibits evoked catecholamine release by altering sensitivity to calcium

Natriuretic peptides are cyclized peptides produced by cardiovascular and neural tissues. These peptides inhibit various secretory responses such as the release of renin, aldosterone and autonomic neurotransmitters. This report tests the hypothesis that atrial natriuretic peptide reduces dopamine efflux from an adrenergic cell line, rat pheochromocytoma cells, by suppressing intracellular calcium concentrations. The L-type calcium channel inhibitor, nifedipine, markedly suppressed dopamine release from depolarized PC12 cells, suggesting that calcium entering through this channel was the predominant stimulus for dopamine efflux. Atrial natriuretic peptide maximally reduced depolarization-evoked dopamine release 20 +/- 3% at a concentration of 100 nM and this effect was abolished by nifedipine, but not by pretreatment with the N-type calcium channel inhibitor, omega-conotoxin, or an inhibitor of calcium-induced calcium release, ryanodine. In cells loaded with Fura-2, atrial natriuretic peptide both augmented depolarization-induced increases of intracellular free calcium concentrations and accelerated the depolarization-induced quenching of the Fura-2 signal by manganese, findings consistent with enhanced conductivity of calcium channels. Dopamine efflux induced by either the calcium ionophore, A23187, or staphylococcal alpha toxin was attenuated by atrial natriuretic peptide. Additionally, a natriuretic peptide interacting solely with the natriuretic peptide C receptor in these cells, C-type natriuretic peptide, also suppressed calcium-induced dopamine efflux in permeabilized cells. These data are consistent with natriuretic peptides attenuating catecholamine exocytosis in response to calcium but inconsistent with the neuromodulatory effect resulting from a reduction in intracellular calcium concentrations within pheochromocytoma cells.     

Inhibitory effect of aldosterone on the natriuretic response to atrial natriuretic peptide in hypocapnic rats

1. Previous studies have shown that acute hypocapnia blunts the natriuretic effect of atrial natriuretic peptide (ANP) independently of the renal nerves and that the effect of ANP is restored by total adrenalectomy. We investigated the natriuretic response to ANP in potassium canrenoate (aldosterone receptor antagonist)-treated rats to clarify whether aldosterone contributes to the attenuated natriuretic response to ANP during hypocapnia. 2. Wistar rats, challenged with either canrenoate or saline vehicle, were infused with 10 micrograms/kg per h ANP during acute hypocapnia achieved by mechanical ventilation. 3. In saline-treated hypocapnic rats, ANP infusion failed to increase the fractional excretion of sodium (FENa) (from 3.49 +/- 0.26 to 5.03 +/- 0.42%, respectively; n = 6) which was similar to values for time control rats (from 3.00 +/- 0.61 to 4.41 +/- 0.68%; n = 6). The hyporesponsiveness to ANP during hypocapnia was also evident when the FENa was compared with that of normocapnic rats (from 3.92 +/- 0.69 to 7.87 +/- 0.45%; P < 0.05; n = 6). In canrenoate-treated rats, ANP infusion caused greater increases in sodium excretion (FENA from 3.05 +/- 0.71 to 7.21 +/- 0.45%; P < 0.05; n = 8) than saline infusion (FENA from 4.16 +/- 1.11 to 5.47 +/- 0.66%; n = 6), despite the hypocapnia. The increase in FENA after ANP infusion during hypocapnia (4.16 +/- 0.86%) was similar to the increase seen during normocapnia (3.89 +/- 0.86%; n = 9). 4. In conclusion: (i) acute hypocapnia blunts the natriuretic effects of ANP; and (ii) this attenuation is restored by potassium canrenoate treatment. The data suggest that aldosterone plays an important role by limiting the renal actions of ANP during acute hypocapnia.     

A novel cardiac hormone related to A-, B- and C-type natriuretic peptides

Mechanisms acting against accumulation of volume are important in pathophysiological situations with volume and salt overload, such as congestive heart failure. Osmoregulating animals that migrate between environments with high and low salinity are ideal models for studying the defence mechanisms against volume gain. We have now cloned and sequenced from salmon (Salmo salar) a cDNA encoding a novel vasorelaxant cardiac hormone of 29 amino acids which is produced by proteolytic processing of a 148-residue preprohormone. Structural and biological results, as well as its distribution indicate that it belongs to an unrecognized family related to natriuretic peptides, perhaps representing an ancestor of ANP and BNP. We have synthesized the 29-amino acid hormone and set up a specific radioimmunoassay. The distribution of the mRNA and peptide is strictly restricted to the heart, with high levels both in the atrium and ventricle in various fish species. The hormone relaxes aortic smooth muscle derived from salmon at nanomolar concentrations. Its release from isolated perfused salmon ventricle is very sensitive to mechanical load: a 10 mmHg load induces a rapid 5-fold increase in hormone release. Our results indicate that the novel cardiac hormone has an important role in fish volume regulation. They also demonstrate that mechanical stimuli have been central to volume regulation since early evolution.     

Effect of propofol infusion on the endocrine response to cardiac surgery

PURPOSE: Bilateral lower extremity venous duplex scanning for acute deep venous thrombosis (DVT) has been advocated because of the high incidence of occult contralateral leg involvement. We investigated the clinical necessity of such a policy. METHODS: The results from 2996 venous duplex studies performed during the past 2 years were retrospectively reviewed. A total of 1694 of these scans were performed on patients with symptoms, of whom 248 (15%) were found to have an acute DVT. Symptoms were limited to one side in 198 patients, whereas bilateral complaints were noted in 50 patients. RESULTS: Among the patients with symptoms of acute DVT, 72 (29%) had bilateral involvement. Bilaterality was more likely in patients with bilateral symptoms than in those with only unilateral symptoms (56% vs 22%; p < 0.005). Of the patients with unilateral symptoms and bilateral DVT, all of them had either acute (80%) or acute and chronic (20%) thrombosis in the symptomatic leg. The contralateral asymptomatic limb had fewer acute and more chronic DVT (41% and 55%, respectively). No patient from the entire group admitted with symptoms had an acute DVT in the asymptomatic limb without a concomitant acute DVT in the symptomatic leg. Unilateral scanning would decrease the examination time by 21% and potentially increase total reimbursement for symptomatic venous scans by 9% compared with routine bilateral duplex scanning. CONCLUSIONS: Although bilateral involvement is frequent in patients with symptoms of acute DVT, treatment in these patients is not altered by this finding. We conclude that contralateral venous scanning in patients with unilateral symptoms is not clinically indicated and that unilateral scanning would result in improved cost-efficiency for vascular laboratories.     

Sex differences in children's response to training on a visual-spatial test.

In a study with 133 children in Grades 1, 3, and 5, a brief training procedure designed to improve performance on the Children's Embedded Figures Test, a test of visual ability, resulted in significant improvement for girls but not for boys. No sex difference was observed among children receiving this training. The implications for theories of sex differences in visual–spatial ability are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Enhanced brain natriuretic peptide response to peak exercise in heart transplant recipients

We investigated the atrial (ANP) and brain natriuretic peptides (BNP), catecholamines, heart rate, and blood pressure responses to graded upright maximal cycling exercise of eight matched healthy subjects and cardiac-denervated heart transplant recipients (HTR). Baseline heart rate and diastolic blood pressure, together with ANP (15.2 +/- 3.7 vs. 4.4 +/- 0.8 pmol/l; P < 0.01) and BNP (14.3 +/- 2. 6 vs. 7.4 +/- 0.6 pmol/l; P < 0.01), were elevated in HTR, but catecholamine levels were similar in both groups. Peak exercise O2 uptake and heart rate were lower in HTR. Exercise-induced maximal ANP increase was similar in both groups (167 +/- 34 vs. 216 +/- 47%). Enhanced BNP increase was significant only in HTR (37 +/- 8 vs. 16 +/- 8%; P < 0.05). Similar norepinephrine but lower peak epinephrine levels were observed in HTR. ANP and heart rate changes from rest to 75% peak exercise were negatively correlated (r = -0.76, P < 0.05), and BNP increase was correlated with left ventricular mass index (r = 0.83, P < 0.01) after heart transplantation. Although ANP increase was not exaggerated, these data support the idea that the chronotropic limitation secondary to sinus node denervation might stimulate ANP release during early exercise in HTR. Furthermore, the BNP response to maximal exercise, which is related to the left ventricular mass index of HTR, is enhanced after heart transplantation.     

Oral administration of arginine enhances the growth hormone response to growth hormone releasing hormone in short children

We have evaluated the effect of oral administration of arginine chlorhydrate on the growth hormone response to growth hormone releasing hormone in a group of nine short prepubertal children (six boys and four girls). Arginine chlorhydrate 10 g, administered orally 60 min before an i.v. bolus injection of growth hormone releasing hormone 1-29, 1 microgram/kg, significantly enhanced the growth hormone response to the neuropeptide, confirming the results of previous studies which used the i.v. route. Furthermore, our data strengthen the view that the effects of arginine chlorhydrate on growth hormone secretion are mediated by inhibition of endogenous somatostatin release.     

Effect of age on the response to parathyroid hormone

Serum phosphate (PO4) levels and the tubular threshold for PO4 corrected for glomerular filtration (TP/GF) are age-dependent, being higher in children than in adults. We evaluated the effect of age on the response to infusion of parathyroid hormone(1-34) (PTH) in healthy children (n = 8) and adults (n = 12). In addition, six patients with pseudohypoparathyroidism (PHP) and two with PTH deficiency (hypoparathyroidism [HP]) were also studied. At baseline, TP/GF in normal subjects was inversely correlated with urinary cyclic adenosine monophosphate corrected for glomerular filtration (UcAMP/GF) (P < .0359). After PTH administration in the controls, UcAMP/GF was inversely correlated with TP/GF (P < .0007) and directly correlated with maximal fractional extraction of PO4 (FEP) (P < .0002). The slope of the regression of TP/GF (P < .0076) and FEP (P < .0034) with UcAMP/GF was steeper in children than in adults. Two HP patients had high PTH-stimulated UcAMP/GF levels, but stimulated TP/GF and FEP were not changed commensurate with levels that would expected from the normative data. In six patients with PHP, PTH-stimulated TP/GF was also correlated with peak UcAMP/GF (r = .96, P < .002). PHP patients could be distinguished from normal controls based on the combination of low peak FEP or high TP/GF together with low peak UcAMP/GF. Thus, in normal subjects, the phosphaturic response to PTH is correlated with the increase in urinary cAMP and is age-dependent, with a greater decrease of TP/GF in children than in adults.     

Adrenal cortex response to adrenocorticotropic hormone in dairy cattle

Adult dairy cows were treated with a range of doses (0.0125mg to 0.4mg) of synthetic ACTH1-24 and the plasma cortisol response was measured. Peak response was independent of dose. Higher doses of ACTH had a more prolonged effect such that the integrated response was dose dependent. Dose response curves were examined by regression analyses. Individual cows had a significant effect on y-axis intercept but not on the slope of the regression lines examined. A dose rate of 0.05mg ACTH iv was identified as a suitable dose rate for use in clinical assessment of adrenal cortex function, with 0, 50 and 120 min following ACTH being critical sampling times to identify the response.     

Enhanced endocrine response to novel environment stress and endotoxin in Lurcher mutant mice

Although electron microscopy no longer enjoys the important role in the diagnosis of interstitial lung diseases that it had in the 1960s and 1970s, it remains an important adjunct in the differential diagnosis of certain pulmonary diseases. Examples include various manifestations of systemic lupus erythematous pneumonitis, in which the presence of tubuloreticular structures and electron-dense deposits are useful for diagnosis; immotile cilia disorders, in which qualitative and now quantitative studies of the cilia of respiratory epithelial cells can help to establish the diagnosis; infections by viruses and other subcellular microorganisms as shown by the role played by electron microscopy in the initial diagnosis of the Hantavirus pulmonary syndrome; pneumoconioses, in which, in conjunction with elemental analysis probes, scanning electron microscopy is of critical importance in establishing the presence of offending foreign compounds in lung tissue or fluids; pulmonary fibrilloses, such as amyloidosis, light chain disease, and fibrillary glomerulonephritis, affecting the lung; and cases of alveolar proteinosis or Langerhans cell granulomatosis diagnosed from fluids such as bronchoalveolar lavages or small tissue samples. As important, electron microscopy remains of enormous usefulness in the study of early structural events leading to the pathogenesis of diseases. For example, recent uses of the technique have focused on the alveolar-capillary wall damage induced by alveolitis in hypersensitivity pneumonitis and sarcoidosis. In summary, electron microscopy remains a useful method in the study and diagnosis of some interstitial lung diseases, but because of its expense it is incumbent on the clinician to use good judgment in the selection of cases and diseases for study by this method.