bluuebunny/crossref_metadata_2025_split huggingface dataset:
ANDROGEN LEVELS DURING CYPROTERONE ACETATE AND ETHINYL OESTRADIOL TREATMENT OF HIRSUTISM
Authors: RUBENS R. 
Published: March 2008

SUMMARYAndrogen levels were measured before and during 12 months of treatment with cyproterone acetate (50 mg 5th to 16th day of cycle) and ethinyl oestradiol (50 μg 5th to 26th day of cycle) in 26 patients suffering from dysfunctional hirsutism. Patients were included in whom androgen levels after a dexamethasone suppression test fell above the range found in normal non‐hirsute women on dexamethasone. Eighty percent of patients showed a substantial improvement of their Ferriman and Gallwey score after 12 months of treatment. During the treatment the mean level of testosterone was 64%, androstenedione 55%, testosterone oestradiol binding globulin 365%, apparent free testosterone 30%, dihydrotestosterone 74%, 5‐androstanediol 43%, dehydroepiandrosterone 44%, 5‐androstenediol 67% and dehydroepiandrosterone sulphate 74% of basal levels. From the results it is concluded that this treatment is effective both clinically and biochemically in reducing hyperandrogenism.
FAMILIAL ACROMEGALY
Authors: JONES M. K. , EVANS P. J. , JONES I. R. , THOMAS J. P. 
Published: March 2008

SUMMARYAn uncle and nephew with acromegaly are described. Two other families with acromegaly have been reported by others and three other possible cases are reviewed. Our patients are unlikely to form part of the multiple endocrine neoplasia (MEN) type 1 syndrome because of the absence of other endocrine disease at an advanced age. A family history of acromegaly should be considered in those presenting with the disease.
A RECEPTOR ASSAY FOR THE MEASUREMENT OF TSH RECEPTOR ANTIBODIES IN UNEXTRACTED SERUM
Authors: SOUTHGATE KAY , CREAGH FIONUALA , TEECE MICHELLE , KINGSWOOD C. , SMITH B. REES 
Published: March 2008

SUMMARYA receptor assay for TSH receptor antibodies is described in which unextracted serum, detergent solubilised TSH receptors and 125I‐labelled TSH are used. The assay was rapid and reproducible with coefficients of inter‐assay variation of 12·3%, 2·1 and 2·6% at mean inhibition of TSH binding values of 11, 53, and 79 respectively. Assay sensitivity could be increased by reducing the volume of receptors used but some increase in the scatter of values obtained with individual normal sera was also observed. Comparison of human and porcine TSH receptor preparations indicated that porcine tissue gave greater sensitivity. Analysis of different groups of patients and normal subjects (n= 21) showed the absence of detectable TSH receptor antibody activity in 16 patients with rheumatoid arthritis, 10 with multinodular goitre and 12 with Hashimoto's disease. However the antibody was readily detectable in 28 out of 28 GRAVES' patients (treated and untreated) who were hyperthyroid at the time of assay.
EFFECT OF ANDROGENS ON PLASMA SOMATOMEDIN‐C/INSULIN‐LIKE GROWTH FACTOR I RESPONSES TO GROWTH HORMONE
Authors: CRAFT W. H. , UNDERWOOD L. E. 
Published: March 2008

SUMMARYIn search of the mechanism for the relatively high plasma somatomedin‐C (Sm‐C) concentrations in pubertal boys and girls, we have measured the plasma Sm‐C responses to exogenous growth hormone (GH) in prepubertal hypopituitary boys before and after testosterone administration. Sm‐C responses were determined in 5 hypopituitary boys (9–14 years of age) who were given two successive injections of GH (0·1 U/kg) 48 h apart. Eight days later, after administering 200 mg testosterone IM, their Sm‐C responses to the same GH challenge were reassessed. There were no significant differences between the pre‐testosterone Sm‐C response to GH and the post‐testosterone response, despite evidence for reductions in 24 h urinary nitrogen excretion and serum urea nitrogen concentrations in response to testosterone. The results provide no evidence that androgen augments the effect of GH to raise plasma Sm‐C during puberty, or that androgen has a direct stimulatory effect on Sm‐C production. By inference and from published reports, it appears more likely that a sex hormone‐stimulated increase in GH secretion is responsible for the increased Sm‐C observed during puberty.
INFUSION OF GRADED CONCENTRATIONS OF SOMATOSTATIN IN MAN: PHARMACOKINETICS AND DIFFERENTIAL INHIBITORY EFFECTS ON PITUITARY AND ISLET HORMONES
Authors: SKAMENE A. , PATEL Y. C. 
Published: March 2008

SUMMARYThe resent study was undertaken (1) to determine the plasma levels of somatostatin‐like immunoreactivity (SLI) during constant infusion of graded concentrations of synthetic somatostatin‐14 (S‐14); (2) to determine the half‐life (t1/2) and metabolic clearance rate (MCR) of SLI; (3) to correlate the plasma SLI levels with the degree of inhibition of pituitary and islet hormone secretion and (4) to establish whether the plasma SLI levels capable of inhibiting pituitary and islet hormone secretion fall into the physiological range. Four normal subjects on separate occasions were each infused with saline or S‐14 (25, 50, and 75 μg/h) at a constant rate for 2 1/2 h. Thirty min following the infusions, TRH (200 μg) and arginine (0·5 g/kg) were given i.v. Blood samples were drawn every 15 min for measurement of GH, TSH, insulin, glucagon and SLI (by RIA of acid‐ethanol extracted plasma) and at rapid intervals for 10 min after stopping the infusions for measurement of SLI disappearance. During S‐14 infusions, plasma SLI rose rapidly, reached a plateau from 15–150 min and declined rapidly on cessation of the infusions with a mean t1/2 of 2·72 ± 0·45 min. Mean plateau SLI levels were: 149 ± 3 pg/ml (25 μg/h), 465 ± 35 pg/ml (50 μg/h), and 1244 ± 71 pg/ml (75 μg/h). SLI was cleared rapidly but the MCR exhibited a dose‐dependent decrease from 3225 ± 699 ml/min for the 25 μg infusion to 1249 ± 241 ml/min for the 75 μg/h infusion (P < 0·05). The 25 μg/h infusion dose produced near‐maximal suppression of GH secretion and inhibited insulin secretion but not TSH or glucagon secretion. The intermediate dose significantly inhibited GH, TSH, and insulin but not glucagon whereas the 75 μg/h infusion suppressed all four hormones. In six normal subjects endogenous plasma SLI rose from a basal value of 32·5 ± 4·9 pg/ml to 75·5 ± 9·0 pg/ml following ingestion of a mixed meal. This level was 50% of that resulting from
POSTPARTUM HYPOGONADOTROPHINISM: EVIDENCE FOR INCREASED OPIOID INHIBITION
Authors: ISHIZUKA B. , QUIGLEY M. E. , YEN S. S. C. 
Published: March 2008

SUMMARYTo investigate a proposed role for endogenous opioids in the inhibition of LH: RH‐gonadotrophin release in the postpartum hypogonadotrophic state, LH and FSH responses to naloxone infusion (1·6 mg/h for 2 h) and to a pulse of LHRH (10 μg) were measured in five non breast‐feeding women. Sequential studies were made at four intervals during the first 25 d postpartum. LH and FSH responses to naloxone were absent on Day 10 postpartum, but significant increments were observed in all studies performed between Days 13–25 postpartum. The relative increments of FSH and LH during naloxone varied as the puerperium progressed; a 3‐fold greater release of FSH than LH was found on Day 13 to 15 while the reverse was observed on Day 25. The intermediate days (17–20) yield an equal response. There was a positive linear correlation between the LH and FSH responses to naloxone infusion and to LHRH. These data suggest that the hypogonadotrophinism of the puerperium is due at least in part to increased opioid inhibition of LHRH secretion.
THE FEMINISATION OF GONADOTROPHIN RESPONSES IN INTACT MALE TRANSSEXUALS
Authors: GOH H. H. , RATNAM S. S. , LONDON D. R. 
Published: March 2008

SUMMARYIn castrated animals and hypogonadal men other workers have shown an LH surge following oestrogen administration similar to that found in the normal female. However, there is no evidence that this can be achieved in intact males. We have therefore studied male transsexual patients before and after chronic oestrogen therapy given for at least three months to feminise the body habitus before undergoing plastic surgery. Subjects were assessed for the acute effects of oestradiol valerate on sex steroid hormone levels and gonadotrophin responses to gonadotrophin releasing hormone. The results showed that longterm treatment could transform the normal male pattern of a suppressive eifect of oestrogen on gonadotrophin release to one where the oestrogen increased LH levels and amplified the effect of LHRH on gonadotrophin release. This pattern is similar to that found in normal women and indicates that longterm oestrogen treatment to males can feminise gonadotrophin responses.
FACTORS IN THE CONTROL OF PLASMA RENIN ACTIVITY AND CONCENTRATION IN TYPE 1 (INSULIN‐DEPENDENT) DIABETES
Authors: DRURY P. L. , BODANSKY H. J. , ODDIE C. J. , EDWARDS C. R. W. 
Published: March 2008

SUMMARYPossible factors involved in the control of plasma renin activity (PRA) and concentration (PRC) have been analysed in 49 patients with long‐standing Type 1 diabetes and in 40 healthy controls matched for age and sex. Eighteen of the diabetic subjects were clinically free of all microvascular and macrovascular complications of their disease (Group A); 31 had proliferative retinopathy (Group B). Both lying and standing PRA and PRC were similar in Group A and healthy controls. Mean PRA was 50–115% higher in Group B diabetics than in controls (P<0·001 supine and erect) and 50–70% higher than in Group A diabetics (P<0·05 supine and erect); PRC also was 60% higher in Group B than in Group A (P<0·05 supine and erect). Control subjects showed significant falls in both PRA and PRC with increasing age, while Groups A and B showed significant falls in PRA or PRC with age. Group A showed a significant inverse correlation between systolic blood pressure and supine PRC (r= ‐0·57), but this was not significant in the controls and was completely absent in Group B. With correction for the effect of age there were significant relationships of PRA and PRC with sodium excretion in the controls and in Group A, but not in Group B. PRA and PRC are thus normal in uncomplicated long‐standing Type 1 diabetes, but regulation of renin secretion appears to be impaired in patients with microvascular disease. Renin secretion inappropriate to their blood pressure and sodium status may contribute to maintenance of their relative hypertension.; Correspondence: Dr P. L. Drury, Department of Endocrinology, St Bartholomew's Hospital, London EC1A 7BE.
ABNORMAL DIETARY REGULATION OF ERYTHROCYTE INSULIN RECEPTOR AFFINITY IN NON‐INSULIN‐DEPENDENT DIABETES MELLITUS
Authors: WARD G. M. , NAYLOR B. A. , SARGENT R. M. , TURNER R. C. 
Published: March 2008

SUMMARYDecreased insulin binding to receptors is associated with the insulin resistance of obese and non‐obese non‐insulin‐dependent diabetics. ‘Down Regulation’ by elevated insulin levels has been suggested as the cause, but factors influencing receptor affinity have not been examined. To investigate the control of receptors in diabetes, 10 non‐insulin‐dependent diabetics and 10 normal subjects were studied after 6 d on low and 6 d on high calorie diets of fixed composition (700 and 2800 Kcal/70 kg of ideal body weight). The binding of insulin by erythrocytes of non‐diabetics, as predicted, increased on the low and decreased on the high calorie diets, due to altered affinity. In contrast, the binding in the diabetics did not change significantly, and the responses to the low and high calorie diets were less than in the normal subjects (P < 0·05 and P < 0·001 respectively). Indeed, the insulin binding in all 5 non‐obese diabetics changed in the opposite direction (P < 0·01) to the non‐diabetics, whereas the obese diabetics showed a mixed response. The changes in receptor binding in the diabetics was completely unrelated to the diurnal plasma insulin levels during 24 h studies. We conclude that the dietary regulation of erythrocyte insulin receptor affinity in non‐insulin‐dependent diabetes is abnormal, and insulin receptor affinity is regulated by factors other than insulin. The relation of this abnormality to the insulin resistance needs further investigation.
SPECIFIC SUPPRESSOR T CELL FUNCTION IN A PATIENT WITH GRAVES' DISEASE AND HER HEALTHY IDENTICAL TWIN
Authors: BALÁZS CŠ. , STENSZKY VALERIA , KOZMA L. , FARID NADIR R. 
Published: March 2008

SUMMARYImmunoregulatory defects have been suggested in autoimmune disorders including GRAVES' disease. The finding that Concanavalin A‐induced suppressor T cell function was sub‐optimal in GRAVES' disease has been disputed; a restricted defect in TSH‐receptor antigen‐specific suppressor cells has instead been proposed by Okita et al. (1980). To explore this further, we studied both specific and non‐specific suppressor cell function in a pair of HLA identical twins, one of whom had GRAVES' disease. By contrast to the euthyroid healthy twin and 10 healthy controls (612 cpm/106 cells) the patient's mononuclear cells (MNCs) incorporated more {3H}‐thymidine (7365 cpm/106 cells) in response to thyroid membrane antigen (TMA). Removal of glass‐adherent cells before addition of antigen increased {3H}‐uptake by cells from the healthy twin to 1808 cpm but reduced those from the GRAVES' twin to 3411 cpm. The influence of MNCs cultured with Con A or TMA for 24 h upon {3H}‐thymidine uptake by 2 × 106 indicator cells triggered by Con A for 72 h or TMA for 96 h was taken as a measure of non‐specific and specific suppressor cell function respectively. Both Con A and TMA induced suppressor cells were reduced, the latter to a more marked degree, in the patient compared to the healthy twin; mixing of MNCs from patient and healthy twin in a 1:1 ratio improved the patient suppressor cell function. When the patient's MNCs triggered for 24 h with Con A were mixed in a 1:1 ratio with her fresh MNCs and TMA, less blast transformation was found compared to an equal number of fresh cells (3H‐thymidine uptake 3250 vs 7365 cpm/106). Similarly, preincubated cells from the healthy twin had greater suppressive effect (1820 cpm/106 cells). We conclude that (I) the HLA identical healthy twin has TMA autoreactive lymphocytes regulated by adherent regulatory cells; (2) the increased ratio of helper/suppressor cells in the adherent cell population in the patient leads to a decrease of {3H}incorporation upon their removal; (3) in the patient, the specific suppressor cell defect is more severe than the non‐specific defect; (4) lack of specific TMA induced triggering may be the critical immunoregulatory defect in Graves' disease.
MATERNAL HYPERTHYROIDISM AND CONGENITAL MALFORMATION IN THE OFFSPRING
Authors: MOMOTANI NAOKO , ITO KUNIHIKO , HAMADA NOBORU , BAN YOSHIO , NISHIKAWA YOSHIHIKO , MIMURA TAKASHI 
Published: March 2008

SUMMARYSix hundred and forty‐three neonates from mothers with GRAVES' disease were examined for major malformations of external organs to compare the influence of maternal hyperthyroidism vs. ingestion of methimazole (MMI) during the first trimester on the incidence of congenital malformations. The subjects were divided into four groups according to maternal therapy and thyroid status during the first trimester as follows: (1) infants whose mothers did not receive MMI and were hyperthyroid (Group 1), (2) infants whose mothers did not receive MMI and were euthyroid (Group 2), (3) infants whose mothers received MMI and were hyperthyroid (Group 3) and (4) infants whose mothers received MMI and were euthyroid (Group 4). The prevalence of malformed infants in these four groups was 6·0% (three of 50), 0·3% (one of 350), 1·7% (two of 117) and 0·0% (none of 126), respectively. The incidence in Group 1 was significantly higher than that in Group 2 (P < 0·01). There was no discernible dose dependency of MMI on the occurrence of malformations. These findings suggest that maternal uncontrolled hyperthyroidism may cause congenital malformations and that the beneficial role of MMI treatment outweighs its teratogenic effect, if any.
SALIVARY CORTISOL LEVELS IN TRUE AND APPARENT HYPERCORTISOLISM
Authors: EVANS P. J. , PETERS J. R. , DYAS J. , WALKER R. F. , RIAD‐FAHMY D. , HALL R. 
Published: March 2008

SUMMARYTotal plasma cortisol measurements may be misleading when there are variations in the plasma cortisol‐binding protein capacity resulting from drugs, pregnancy or congenital alterations in cortisol‐binding globulin (CBG). Salivary cortisol levels, which represent the free component of plasma cortisol, are less affected by alterations in protein binding and have been used in the investigation of hypothalamic‐pituitary‐adrenal disorders. This study compares these two indices of adrenal function in conditions of true hypercortisolism and spurious hypercortisolism (resulting from oral contraceptive medication or pregnancy). The circadian variation of cortisol in plasma and saliva was studied in six patients with unequivocal hypercortisolism and compared with normal volunteers. In the normal group, plasma and salivary cortisol levels taken at 0900 h were significantly higher than those taken at 2400 h. Patients with Cushing's syndrome failed to show a significant difference between plasma and salivary cortisol levels collected at 0900 and 2400 h. Five patients with pituitary‐dependent Cushing's disease, one patient with an adrenal carcinoma causing Cushing's syndrome and seven normal subjects each received a dexamethasone suppression test using a continuous infusion of dexamethasone sodium phosphate at a rate of 1 mg/h. There was no significant difference in the half‐life disappearance rate of endogenous cortisol in either plasma or saliva comparing grouped data from patients with pituitary‐dependent Cushing's disease with that of normal subjects. Failure of suppression of both plasma and salivary cortisol levels was observed in the one patient with adrenal carcinoma during dexamethasone infusion. The correlation between plasma and salivary cortisol measurements during the dexamethasone infusion was r=0·989 (P < 0·001) for normals and r= 0·982 (P < 0·001) for Cushing's patients. Measurements of plasma and salivary cortisol were compared in pregnancy and during low dose oestrogen therapy; both these conditions are known to be associated with elevated cortisol binding globulin concentrations. A significant difference was demonstrated between the 0900 h plasma cortisol levels of normal subjects and those both in the third trimester of pregnancy of the oestrogen containing contraceptive pill. No difference was observed in the 0900 h salivary cortisol between control and pregnant or oestrogen treated groups.
EFFECT OF METOCLOPRAMIDE ON ALDOSTERONE AND REGULATORY FACTORS IN MAN
Authors: GILCHRIST N. L. , ESPINER E. A. , NICHOLLS M. G. , DONALD R. A. 
Published: March 2008

SUMMARYTo determine the role of known secretagogues in the aldosterone response to dopamine blocking agents, plasma levels of ACTH, angiotensin II, potassium and plasma catecholamines were measured in five normal male subjects before and after intravenous injection of saline or 10 mg metoclopramide. There were no consistent changes in hormone levels after saline injection. After metoclopramide, plasma aldosterone increased three‐fold to peak values at 20 min post‐injection. A significant increase in aldosterone was observed within 10 min during which period there was no significant change in plasma ACTH, plasma renin activity All or K. Plasma levels of cortisol, noradrenaline, adrenaline and dopamine showed no significant changes after injection of metoclopramide which induced a ten‐fold rise in plasma prolactin. These results provide direct evidence that factors other than the plasma concentration of ACTH, All and K—or fluctuations in plasma catecholamines—are likely to be responsible for the acute increase in plasma aldosterone after metoclopramide injection in normal man.
CHOLINERGIC REGULATION OF PANCREATIC POLYPEPTIDE SECRETION IN CHRONIC RENAL FAILURE
Authors: LAMERS C. B. H. W. , VAN LEUSEN R. , DE JONG A. J. L. , VAN LEER E. , DIEMEL J. M. , PEETOOM J. J. , JANSEN J. B. J. M. 
Published: March 2008

SUMMARYSecretion of pancreatic polypeptide (PP) is regulated mainly by cholinergic mechanisms and we have studied this in patients with chronic renal failure (CRF). Basal serum PP concentrations in 25 patients with CRF (401 ± 80; 116–2100 pmol/1; mean ± SEM and range) were significantly higher than in 65 normal subjects (33 ± 2; 21–120 pmol/1, P<0·001). Ingestion of a standard test meal induced significantly larger increases in serum PP in 11 patients with CRF (304 ± 45; 155–640 pmol/1) than in 11 normal subjects (140 ± 33; 51–440 pmol/1, P < 0·005). Insulin‐hypoglycaemia (0·1 U/kg i.v.) provoked similar increases in serum PP in five patients with CRF (404 ± 79; 170–665 pmol/1) as in five normal subjects (449 ± 92; 180–706 pmol/1). Administration of atropine (1 mg i.v.) did not normalize the elevated basal serum PP concentrations in five patients with CRF. On the other hand, administration of the same dose of atropine 60 min after ingestion of food decreased postprandial serum PP levels to basal values within one hour both in five patients with CRF and in six normal subjects. Sephadex G‐50 column chromatography of basal, postprandial and post‐atro‐pine sera from three patients with CRF revealed at least three different molecular forms. The PP peak coeluting with the 4200 molecular weight human PP standard comprised more than half of total PP immunoreactivity and was the only peak to be influenced by feeding or atropine. We conclude that in patients with CRF, PP secretion stimulated by cholinergic mechanisms is normal. In such patients post‐prandially released PP is dependent mainly upon cholinergic mechanisms, whereas the elevated basal serum PP concentration is not under cholinergic control.
PRELIMINARY EXPERIENCES WITH A BIOASSAY FOR ADRENOCORTICOTROPHIN (ACTH) IN UNEXTRACTED HUMAN PLASMA USING DISPERSED GUINEA‐PIG ADRENAL CELLS
Authors: LAMBERT A. , FROST J. , ROBERTSON W. R. 
Published: March 2008

SUMMARYA simple, accurate and precise dispersed cell bioassay suitable for the assay of ACTH levels >50 ng/1 in unextracted human plasma is described. Isolated adrenal cells were prepared by tryptic digestion of the guinea‐pig adrenal gland and cortisol production by these cells was controlled specifically by ACTH. The cortisol response to 2 ng/1 of human pituitary ACTH (1–39) was always significantly (P < 0·05, n= 17) different from the control. ACTH concentrations between 1 and 20 ng/1 gave a 14 ± 3 fold (n= 17) increment in cortisol response. Dilutions of test plasmas were parallel with standard ACTH (1–39) when the plasma concentrations were maintained throughout at 4% (1 in 25 dilution) by the addition of dexamethasone‐suppressed plasma (‘ACTH free’). Using a 25 fold plasma dilution, the limit of detection of ACTH in unextracted plasma was 50 ng/1. Recovery of ACTH (1–39) spiked into dexamethasone suppressed plasma at concentrations of 250 and 100 ng/1 was 97·10% (n=17) and 114 ± 15% (n= 17) respectively. The within assay coefficient of variation (CV) of both quality control and patients' samples never exceeded 9% while between assay variation was 13%. The sample throughput was 30 plasma samples/week/technician.
PROINSULIN IN HUMAN SERUM: PROBLEMS IN MEASUREMENT AND INTERPRETATION
Authors: GRAY I. P. , SIDDLE K. , DOCHERTY K. , FRANK B. H. , HALES C. N. 
Published: March 2008

SUMMARYThe immunoreactivity of an extracted pancreatic human proinsulin standard in an indirect immunoradiometric assay was found to be at least one hundred times higher than that of biosynthetic human proinsulin. Limited tryptic digestion of the biosynthetic proinsulin increased its immunoreactivity in the assay and this was attributed to the production of partially cleaved proinsulin molecules which still retained the C‐peptide moeity. This inference was confirmed by the finding that pure samples of 65/A1 and 32/33 split proinsulins reacted in the assay very similarly to the pancreatic proinsulin standard. The implications of these results are that the immunoassays of proinsulin using antisera to C‐peptide may recognise the intact proinsulin molecule very poorly, if at all, and that the ‘proinsulin’ measured by such assays of human serum may be largely if not entirely intermediates of proinsulin cleavage.