bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of gonadotrophin releasing hormone antagonist and agonist on the pulsatile release of gonadotrophins and α‐subunit in postmenopausal women*
Authors: Couzinet B. , Lahlou N. , Thomas G. , Thalabard J. C. , Bouchard P. , Roger M. , Schalson G. 
Published: March 2008

SUMMARY objective The present study was designed to further assess the mechanism of action of GnRH and GnRH analogues
design AND PATIENTS Both the Nal‐Glu GnRH antagonist and the D‐Trp6 GnRH agonist were administered sequentially to nine normal, post‐menopausal women. MEASUREMENTS A baseline study of pulsatile LH, FSH and free α‐subunit secretion was performed, with sampling every 10 min for 8 h, and then repeated 8 h after a single subcutaneous injection of Nal‐Glu GnRH antagonist (5 mg). Sampling was repeated 21 days after the intramuscular injection of a depot preparation of D‐Trp6 GnRH (3·75 mg) in the same women.
results The baseline sampling period showed synchronous pulses of LH and free α‐subunit. The antagonist Nal‐Glu decreased plasma LH (71%) and free α‐subunit (43%). However, with the single dose of 5 mg, pulsatile LH and free α‐subunit release were not completely suppressed and remained temporally correlated. The GnRH agonist had a potent inhibitory action on plasma immunoreactive LH (IRMA) (93%). In contrast, it increased the mean plasma levels of free α‐subunit from 1·66·0±01 to 5·06·0±02 μ g/l (205%). The pulsatile secretory patterns of both LH and free α‐subunit were abolished by the agonist. Immunoreactive FSH levels were decreased by the antagonist (24%) and suppressed by the agonist (93%).
conclusions The pulsatile study confirms the different mechanism of action of GnRH analogues. Following antagonist administration, low amplitude free α‐subunit pulses persist and are synchronous with residual LH pulses. In contrast, LH and free α‐subunit are not maintained under agonist treatment. These data provide evidence for the differential regulation of LH and free α‐subunit by GnRH.
Corticosteroid‐induced growth hormone secretion in normal and obese subjects
Authors: Muruals Covadonga , Cordidot Fernando , Moralesf Maria J. , Casanueva Felipe F. , Dléguez Carlos 
Published: March 2008

SUMMARY objective In normal subjects, cortlcosterolds stimulate growth hormone (GH) secretion at 3 hours. Obesity is associated with blunted GH secretion. In order to clarify both the deranged mechanism of GH secretion In obesity and the corticosterold mechanism of action we have assessed In normal and obese subjects the effects of dexamethasone, pyridostigmine (a drug capable of suppressing somatostatln release) and GHRH. We also compared in normal subjects the stimulatory effect of three different cortlcosterolds on plasma GH levels design In both normal and obese subjects the following tests were carried out: placebo; dexamethasone alone (4 mg l.v. at 0 minutes); and dexamethasone plus pyridostigmine (120 mg p.o. at 60 minutes)In normal subjects we also studied the effects of hydrocortisone (100 mg l.v. at 0 minutes) and deflazacort (a corticosteroid that does not cross the blood‐brain barrier) (60 mg l.v. at 0 minutes). In obese subjects we also assessed the effect of dexamethasone plus GHRH (100 μ g l.v. at 150 minutes) on plasma GH levels. patients Ten normal subjects and 22 obese subjects were studied. Normal controls were within 10% of their ideal body weight. Obese subjects had a body mass Index of 37·1±1·1 (mean ± SEM) measurements Plasma GH levels were measured by radioimmunoassay. results Dexamethasone‐induced GH secretion In normal subjects (28·6±7·8 mμ/l, P > 0·05). Cortlcosterolds did not alter GH levels In obese subjects. Pretreatment with pyridostigmine increased dexamethasone‐induced GH release in normal subjects (40·8±6·8 mμ/l) but this did not achieve statistical significance. Dexamethasone plus pyridostigmine did not alter GH levels In obese subjects (8·0±1·6 mU/l). In some subjects, dexamethasone protreatment potentiated GHRH‐stimulated GH secretion, while In half the subjects the basal GH levels were not altered.In control subjects, hydrocortisone and deflazacort caused GH release similar to dexamethasone conclusions Corticosteroids are a new and selective stimulus of GH secretion. They do not cause GH release in obese subjects. Their relative independence from chollnergic control suggest that they act by reducing somatostatin secretion
Effects of pyridostigmine on spontaneous and growth hormone‐releasing hormone stimulated growth hormone secretion in children on daily glucocorticoid therapy after liver transplantation
Authors: Giustina Andrea , Girelli Angela , Albert Danlele , Bossonl Simonetta , Buzl Fabio , Doga Mauro , Schettino Maurlzlo , Wehrenberg William B. 
Published: March 2008

SUMMARY objectives We aimed to investigate both nocturnal spontaneous and morning growth hormone (GH)‐releasing hormone (GHRH)‐induced GH secretion in children on daily glucocorticoid treatment after liver transplantation and to evaluate the effect of pyridostigmine (an acetylcholinesterase inhibitor thought to reduce hypothalamic somatostatin tone) on GH secretion in these patients design We performed a randomized, single‐blind, crossover study patients We studied three male and three female Juvenile patients, within a year of orthotopic liver transplantation and under immunosuppressive glucocorticoid therapy (mean dose ± SEM, 5·92·0±63 mg/day) and five normal children (four males, one female) measurements Both nocturnal spontaneous and morning GHRH‐induced GH secretion were evaluated after administration of placebo, 1 tablet P.O., or pyridostigmine, 2 mg/kg p.o results Spontaneous GH. Placebo: in liver transplanted children nocturnal GH secretion (mean GH level 10·8±2·0 mU/l) was not significantly different with respect to normal children (mean GH level 12·8±1·2 mU/l); pyridostigmine: nocturnal GH secretion was significantly Increased as compared to placebo In subjects with liver transplantation but not In normal children. GHRH test. Placebo: liver transplanted patients showed a blunted GH response to GHRH with respect to normal children; pyridostigmine: the GH responses to GHRH (P > 0·05) Increased as compared to placebo and did not differ sign If Icantly In the two groups. conclusions Our data suggest a steroid‐mediated increase in hypothalamic somatostatin tone in liver transplanted children
Effects of ambient glycaemic state on growth hormone responsiveness in insulin‐dependent diabetes
Authors: Ismail I. S. , Scanlon M. F. , Peters J. R. 
Published: March 2008

SUMMARY objective We wished to examine the effects of ambient glycaemla on hypothalamic somatostatlnerglc tone In Insulin‐dependent diabetes mellitus design After 6‐hour periods of either euglycaemla (15 mmol/l) or hyperglycaemia (15 mmol/l), exercise‐induced GH secretion was measured patients Seven insulin dependent diabetics with no evidence of complications were recruited results There was no significant difference between basal GH levels during euglycaemla and hyperglycaemia (5·50 vs 5·53 mU/l). Nor was there a significant difference when mean Δ GH levels (33·9 vs 27·4 mU/l) or mean area under GH curve (2331 vs 4038 mU min/l) during euglycaemia or hyperglycaemia were compared. conclusions We find no evidence therefore to support short‐term effects of ambient glucose concentration on GH responsiveness, and by inference no direct effect of short‐term changes in glycaemic control on hypothalamic release of somatostatln in the aetiology of GH hypersecretion In insulin‐dependent diabetes mellitus
Circulating levels of inhibin in pregnant women at term: simultaneous disappearance with oestradiol and progesterone after delivery
Authors: Kettel L. M. , Rosati S. J. , Bangah M. L. , Burger H. G. , Yen S. S. C. 
Published: March 2008

SUMMARYCirculating levels of immunoreactive inhibin (ir‐inhibin) and its disappearance after delivery of the placenta were determined in seven pregnant women at term. Serum cestradiol (E2) and progesterone (P4) levels were measured simultaneously and served as comparisons. Fetal contributions of ir‐inhibin were asessed by determining concentrations in the umbilical artery (UA) and vein (UV). Relative changes in circulating levels of ir‐inhibin, E2, and P4 were compared to levels found in nonpregnant women during the early follicular phase (EFP) and mid‐luteal phase (MLP) of the normal menstrual cycle. In pregnant women, ir‐inhibin levels at delivery were 15‐ and 3‐fold higher than EFP and MLP values respectively. The disappearance of all three hormones after removal of the placenta followed a bi‐exponential curve with an initial, rapid component and a second, slower component. There was a highly signifiant positive correlation between the disappearance curves of all three placental hormones (r = 0–97, P > 013001). Concentrations of ir‐inhibin in the cord blood were about half that in maternal serum and without significant difference between levels in UA and UV.
The pathogenesis of the ovarian hyperstimulation syndrome (OHS): a possible role for ovarian renin
Authors: Ong A. C. M. , Eisen V. , Rennie D. P. , Homburg R. , Lachelin G. C. L. , Jacobs H. S. , Slater J. D. H. 
Published: March 2008

SUMMARYTwo patients with severe ovarian hyperstimulation syndrome are described. Increased plasma concentrations of immunoradlometrically determined total renin are shown, together with greatly increased plasma levels of active renin and aldosterone. These very high values for total renin, renin activity and aldosterone were not suppressed when extracellular compartments were greatly expanded; the values subsequently declined to normal levels, despite the use of diuretics. This suggested that the renin was of non‐renal origin since its production was apparently unaffected by influences which control juxtaglomerular secretion. The high concentrations of the rennin—angiotensin—aldosterone system suggest that it contributes to the genesis of the ovarian hyperstimulation syndrome
Use of ketoconazole in the treatment of Cushing's disease and ectopic ACTH syndrome
Authors: Tabarin A. , Navarranne A. , Guérin J. , Corcuff J. ‐B. , Parneix M. , Roger P. 
Published: March 2008

SUMMARYKetoconazole, an imidazole derivative which Inhibits adrenal steroidogenesis, has been used with success for the metabolic control of Cushing's disease. Few data are available about the use of ketoconazole in the management of the ectopic ACTH syndrome. We have used ketoconazole in eight patients: four patients with Cushing's disease, two patients with overt and two with occult ectopic ACTH syndrome. Among patients with Cushing's disease, reversible hypoadrenalism occurred once. All had full clinical and biochemical regression of the disease for more than 6 months with 400–1200 mg ketoconazole per day. Patients with ectopic ACTH syndrome received 1200 mg ketoconazole per day for at least 2 months. Partial biochemical regression was observed in two and a secondary escape to adrenal blockade in two others. These findings further indicate that ketoconazole is a valuable tool for the metabolic control of Cushing's disease. On the contrary, in ectopic ACTH syndrome, this aim can be impossible to reach with ketoconazole although the reasons for its ineffectiveness remain to be determined.
Long‐term follow‐up of treatment of thyrotoxicosis by three different methods
Authors: Franklyn Jayne A. , Daykin Jackie , Drolc Zorka , Farmer Malcolm , Sheppard Michael C. 
Published: March 2008

SUMMARYIn view of continuing debate regarding the best definitive therapy for thyrotoxicosis, we examined the long‐term outcome of radiolodine (131I) or surgical treatment of 1918 thyrotoxic patients divided into three groups: those given 131I at a dose calculated from thyroid size, 131I uptake and effective half‐life to administer a fixed radioactivity dose to the thyroid; those treated with a dose of 131I (110,185 or 370 MBq) chosen empirically; and those treated by partial thyroidectomy. A minimum 10‐year follow‐up was achieved for 1119 patients treated with a calculated 131I dose; a single dose resulted in control of disease in 90.5|X%. At 5 years, 18|X% were hypothyroid, the prevalence rising to 42|X% at 20 years. Of 504 patients treated with an empirical 131I dose and followed for at least 5 years, thyrotoxicosis was controlled by a single dose in 89.7|X%. The rate of hypothyroidism at 5 years (38.5|X%) was higher than that found in the calculated dose group. A minimum 10‐year follow‐up was achieved for 295 surgically treated patients; thyrotoxicosis was controlled in 89.2|X%. The prevalence of hypothyroidism (2|X% at 5 years, 27.5|X% at 20 years) was lower than that found after 131I, whether given by calculated or empirical dose. Each of the treatments employed resulted in an acceptable rate of cure of thyrotoxicosis. If maintenance of euthyroidism is the major objective, our findings suggest that surgery represents the treatment of choice. Furthermore, calculated dose 131I administration has advantages in terms of risk of hypothyroidism over empirical dose treatment. In choosing treatment, these apparent advantages of partial thyroidectomy and calculated 131I doses over empirical doses of 131I must be weighed against surgical morbidity, cost and patient inconvenience.
Increased growth hormone response to growth hormone releasing hormone induced by erythropoietin in uraemic patients
Authors: Cantalamessa L. , Cremagnani L. , Orsatti A. , Vigna L. , Buccianti G. 
Published: March 2008

SUMMARYThis study was designed to assess the response of growth hormone (GH) to growth hormone releasing hormone (GHRH) and the possible interaction of acutely administered recombinant human erythropoietin (rhEPO) on GH response to GHRH in a group of uraemic patients. Eight patients on maintenance haemodialysis, not previously treated with rhEPO, and six healthy controls were tested with GHRH (100 μg i.v. in bolus), and with GHRH (100 μg i.v. in bolus) plus rhEPO (40 U/kg in constant infusion for 30 min) on different days. GHRH injection provoked a GH release in five out of eight uraemic patients; the overall mean response did not differ significantly from the GH response obtained in controls (P = 0.30). Erythropoletin infusion significantly increased GH release after GHRH (P > 0.01 at 15, 30, 45, 60 min after GHRH injection) in uraemic patients; in controls, on the contrary, stimulation with GHRH plus rhEPO did not induce a greater increase of OH release compared with that observed after GHRH alone (mean GH peak 37.66 |Mp 7.68 mU/I after GHRH; and 38.0 |Mp 9.18 mU/I after GHRH plus rhEPO; P < 0.5). In this study acutely administered rhEPO significantly potentiated the GH response to GHRH in uraemic patients whereas the same effect was not demonstrable in subjects with normal renal function.
Cyproterone acetate for severe hirsutism:results of a double‐blind dose‐ranging study*
Authors: Barth J. H. , Cherry C. A. , Wojnarowska F. , Dawber R. P. R. 
Published: March 2008

Summary. objective The objective was to determine If cyproterone acetate (CPA) therapy lor hirsute women demonstrated a dose response.design A double‐blind dose‐ranging study of the effect of 3 doses of cyproterone acetate for a period of 12 months.patients Twenty‐one hirsute women received the Dlanette contraceptive pill (35μ ethinyl oestradlol+2 mg CPA, Sobering Healthcare, UK, 20 received Dlanette plus 20 mg CPA and 19 received Dlanette plus 100 mg CPA: supplementary CPA was administered on days 1–10 of the birth control pill cycle as described by Hammersteln.measurementsHair growth was measured using the clinical scale of Ferrlman and Gallwey and by direct measurement of hair shaft diameter and linear growth of hair on the face, forearm, abdomen and thigh.results Thirty‐eight women completed 12 months therapy, eight withdrew due to side‐effects and 14 were lost to follow‐up. All three dose schedules produced significant reductions In clinical hair growth scores. This reduction was seen after 6 months with Dlanette alone (P< 0.005) and after 3 months with both the higher doses (P< 0.01). There were no significant differences between the effect of different doses at any of the three‐monthly time points. Hair diameter measurements were reduced by all doses after 12 months:face by 27*, 37, 37%*, forearm 5, 10, 8%*, abdomen 22*, 39*, 33%*, thigh 12, 24*, 30%* (median reductions (*P< 0.01) for Dianette, D + 20 mg CPA and D + 100 mg CPA respectively. There were no significant reductions in daily linear growth rates. A comparison of the percentage reduction In hair shaft diameter at each site demonstrated no significant difference between doses, although the reductions by the three doses on the forearm, abdomen and thigh suggested a trend towards a dose response.conclusions We conclude that cyproterone acetate 2 mg daily appears to be as effective as higher doses in the therapy of hirsute women.
Critically ill patients have high basal growth hormone levels with attenuated oscillatory activity associated with low levels of insulin–like growth factor‐I
Authors: Ross Richard , Miell John , Freeman Emma , Jones Jennifer , Matthews David , Preece Michael , Buchanan Charles 
Published: March 2008

Summary. objective The aim was to study the relationship between growth hormone (GH) and insulin‐like growth factor‐I (IGF‐I) in critically ill patients.design Case‐control study of critically ill patients admitted to the intensive care unit was carried out.patients Six critically ill patients (51–78 years) who required ventilation and parenteral nutrition and six age, weight, height, and sex‐matched healthy adults were studied.measurements The patients and controls were studied for two 24‐hour periods; the patients before and after starting parenteral feeding, and the controls during a 36‐hour fast and when taking meals equivalent in calories and protein to the patients' parenteral feed. Serum GH was measured at 20‐minute intervals and analysed by a pulse detection algorithm (Pulsar) and Fourier transformation. IGF‐I was measured at 0, 12, and 24 hours.results Patients had low serum IGF‐I levels compared with controls, whether fasted or fed, despite having mean GH levels similar to fasted controls. For fasted patients va fasted controls the mean (1 SD) GH levels were 4.5 . 2.0 vs 4.0 × 2.4 mU/l respectively, and IGF‐I levels at the end of the fast were 0.17 × 0.11 vs 0.78 × 0.29 U/ml (P=0.003). Patients showed elevated baseline GH levels compared with controls when fasted and during parenteral feeding (patients vs controls fasted 3.1 × 1.9 vs 0.8 × 0.5 mU/l, P= 0.01; patients vs controls fed 4.2 × 4.5 vs 0.5 × 0.04 mU/l, P= 0.028). Fourier transformation confirmed oscillatory GH levels in the controls, fasted or fed, but this activity was attenuated in the patients. Parenteral feeding had no effect on the GH profiles or IGF‐I levels of patients, but controls showed greater mean GH levels during their fast than when fed.conclusions We have demonstrated that critically ill patients have low IGF‐I levels associated with augmented baseline GH levels which show reduced oscillatory activity. The results would be compatible with the hypothesis that there is an adaptive change in critically ill patients away from the indirect effects of GH (stimulation of IGF‐I production and anabollsm) and toward the direct effects (lipolysis and Insulin antagonism) which increase the availability of energy substrates. The pattern of GH levels seen In our patients may be important in this adaptation.
Cell kinetics in parathyroid adenomas: evidence for decline in rates of cell birth and tumour growth, assuming clonal origin
Authors: Parfitt A. M. , Wlllgoss D. , Jacobi J. , Lloyd H. M. 
Published: March 2008

Summary. objective We aimed to provide a cell kinetic explanation for the demonstrated lack of disease progression in most patients with mild, asymptomatic primary hyperparathyroldism.design We compared cell birth rates, estimated at the time of adenoma excision, with the lowest birth rates needed to grow tumours of the observed size.patients Sixty‐three patients with primary hyperparathyroldism due to a single chief cell adenoma who had normal renal function were followed up for long enough to demonstrate cure after surgical excision.measurementsFresh adenoma tissue was incubated with trltlated thymldine. The proportion of cells synthesizing DNA was determined directly by radloautography in 18 cases, and indirectly from the regression of label index on rate of DNA synthesis in 45 cases. The birth rate of new cells was calculated assuming the duration of S phase to be 12 hours. The number o° cells In each adenoma was estimated both from parenchymal weight and from total DNA content, and the minimum birth rate needed to produce this number of cells from a single cell, beginning in utero, was calculated on an exponential model.results The mean observed birth rate of new cells (mean (SD)) was 17.3 (11.1)%/year, and the minimum needed birth rate was 4.28 (21.6)%/year, significantly, (P < 0.001) higher than the observed birth rate.conclusions The rate of mitosis had fallen substantially during the life span of most parathyroid adenomas. To account for this, we propose that the mutation impiled by a clonal origin increases the secretory setpolnt. Because proliferation, as well as hormone secretion, is influenced by calcium In parathyroid cells, the expected result would be rapid initial growth, slowing down as tumour size reached an asymptotic value corresponding to the total rate of hormone secretion needed to raise the plasma calcium to the new setpolnt.
Osmotic and non‐osmotic regulation of thirst and vasopressin secretion in patients with compulsive water drinking
Authors: Thompson C. J. , Edwards C. R. W. , Baylis P. H. 
Published: March 2008

Summary. objective To examine the osmotic and non‐osmotic regulation of thirst and AVP release In patients with compulsive water drinking.design A 2‐hour Intravenous Infusion of hypertonic (855 mmol/l) sodium chloride solution, followed by a 2‐hour drinking period.patients Seven patients with compulsive water drinking, seven patients with diabetes insipidus and seven healthy controls.measurements Plasma AVP, osmolality, sodium and haematocrit, thirst ratings on a visual analogue scale and the volume of water drunk in 2 hours following Infusion. RESULTS Plasma AVP responses to osmotic stimulation, and non‐osmotic inhibition by drinking, were normal In patients with compulsive water drinking. Basal thirst ratings were higher in compulsive water drinking than in either diabetes (P < 0.001) or controls (P < 0.001), despite lower basal plasma osmoialities. There was a significant rise In thirst ratings during saline infusion, which correlated closely with plasma osmolality, in all three groups, but the final thirst ratings were higher in compulsive water drinkers, who subsequently drank more water than In either diabetes insipidus (P < ‐0.01) or controls (P < 0.001). Drinking rapidly lowered thirst ratings in controls and diabetes insipidus before changes occurred in plasma osmolality, but remained elevated in patients with compulsive water drinking. Linear regression analysis defined a lower osmotic threshold for thirst in compulsive water drinking compared with controls or diabetes insipidus.conclusionsThere are abnormalities of the osmotic stimulation and non‐osmotic inhibition of thirst in compulsive water drinking, suggesting that the underlying defect is one of interpretation of osmotic and non‐osmotic inputs. Measurement of thirst responses during hypertonic saline infusion and subsequent water drinking may provide useful diagnostic Information in the differentiation of polyuric states.