bluuebunny/crossref_metadata_2025_split huggingface dataset:
MUSCARINIC CHOLINERGIC MEDIATION OF LHRH‐INDUCED LH AND FSH SECRETION IN NORMAL MEN
Authors: CHIODERA P. , VOLPI R. , D'AMATO L. , PETROLINI R. , SALATI G. , FERRARI P. , FAVA A. , COIRO V. 
Published: March 2008

SUMMARYLHRH (100 μg i.v. bolus) was given to six young healthy men under basal conditions and after the administration of pirenzepine (10, 20, 30 or 40 mg i.v. 10 min before LHRH), which is a selective blocker of muscarinic cholinergic receptors. Pretreatment with 10 mg of pirenzepine did not modify LH and FSH responses to LHRH, whereas larger amounts of the drug significantly reduced gonadotrophin responses to LHRH. A dose‐related effect of the drug was not observed, since a maximal reduction of LHRH‐induced gonadotrophin secretion was already present when 20 mg of pirenzepine were used. When the effect of pirenzepine (20 mg) on the basal concentrations of FSH and LH was studied in four additional sex and age matched subjects, no significant changes were observed for at least 120 min after the injection. These results demonstrate that LHRH‐induced LH and FSH secretion involves a muscarinic cholinergic mechanism.
HIGH MOLECULAR WEIGHT VASOPRESSIN: DETECTION OF A LARGE AMOUNT IN THE PLASMA OF A PATIENT
Authors: SMITZ S. , LEGROS J.‐J. , FRANCHIMONT P. , LE MAIRE M. 
Published: March 2008

SUMMARYUsing a sensitive and specific radioimmunoassay for arginine‐vasopressin, we have searched for the presence of high molecular weight (HMW) vasopressin in the plasma of a patient with the syndrome of inappropriate antidiuretic hormone secretion (SIADH) and an oat cell carcinoma of the lung. After incubation in 8 mol/l urea, one millilitre of the plasma from this patient was fractionated on a Sephadex G‐50 column and the immunoreactive vasopressin content was evaluated before and after trypsin treatment of the eluted fractions. A wide peak of apparent mol. wt. 2500–6000 daltons was revealed only after tryptic digestion of each fraction. This peak contained the equivalent of 1900 pg of vasopressin. A tryptic digest of this peak, rechromatographed on Sephadex G‐25, gave two small peptides the major one eluting at a position identical to vasopressin. These results demonstrate the presence of a large amount of HMW vasopressin in the plasma of a patient with SIADH and oat cell carcinoma of the lung.
5α‐REDUCTASE ACTIVITY IN HUMAN PROSTATE CANCER IS RELATED TO THE HISTOLOGICAL DIFFERENTIATION OF THE TUMOUR
Authors: HABIB F. K. , BUSUTTIL A. , ROBINSON R. A. , CHISHOLM G. D. 
Published: March 2008

SUMMARYWe have measured the activities of two androgen metabolizing enzymes in tissue obtained from thirty‐nine patients with carcinoma of the prostate (CaP). The enzyme activities were correlated to the histological differentiation of the tumours based on the Gleason Score and also compared to the activities measured in fourteen age matched patients with nodular prostatic hyperplasia (BPH). Although the mean values for the 5α‐reductase in CaP (9·29 ± 1·47 pmol/mg protein/30 min) were found to be significantly lower than the corresponding values in BPH (16·26 ± 3·04 pmol/mg protein/30 min) (P < 0·05), there were nonetheless significant differences within the cancer group and these were totally dependent on the degree of differentiation of the tumour. A progressively suppressed enzyme activity was measured as the carcinomatous tissue became more anaplastic. No correlation was, however, observed between tumour bulk which was also estimated histologically and 5α‐reductase, indicating that the activity of this enzyme is purely a function of the histological grade of the cancer and as such 5α‐reductase could be used as a biochemical marker for tumour differentiation.We also measured the 3α(β)‐hydroxysteroid dehydrogenase activities in cancer of the prostate but our findings indicated no significant differences between the various stages of the cancer. Furthermore we were unable to correlate the activities of this enzyme with that of the 5α‐reductase. Nonetheless two interesting patterns relating to the 3α(β)‐hydroxysteroid dehydrogenase emerged. Whilst in BPH the activity of this enzyme was confined to a very narrow range (1·04 ± 5·27 pmol/mg protein/30 min), there was a wide spread in the activities of the cancerous specimens with the highest 3α(β)‐hydroxysteroid dehydrogenase activity being usually manifested in specimens with a low 5α‐reductase. Since the capacity of some cancerous specimens to metabolize
FAILURE TO SUPPRESS C‐PEPTIDE SECRETION BY EUGLYCAEMIC HYPERINSULINAEMIA: A NEW DIAGNOSTIC TEST FOR INSULINOMA?
Authors: YKI‐JÄRVINEN H. , PELKONEN R. , KOIVISTO V. A. 
Published: March 2008

SUMMARYIn order to study the suppression of C‐peptide secretion in 5 patients with insulin‐producing tumours or beta cell hyperplasia, we raised and maintained plasma insulin at a high physiological level and kept plasma glucose unchanged for 2 h with combined infusions of glucose and insulin (insulin clamp technique). No suppression of C‐peptide secretion was seen in any of the patients, in contrast with a 35‐65% decline seen in each of 17 healthy control subjects. In 3 patients surgical removal of beta cell adenoma normalized the response, whereas it remained unchanged in a patient with beta cell hyperplasia after partial pancreatectomy and in another with inoperable carcinoma. These results indicate that insulin secretion by insulinomas is characterized by lack of suppression by insulin. Measurement of the insulin‐insulin feedback loop by the clamp technique may provide a rapid test to reveal autonomous insulin secretion without the risk of hypoglycaemia.
CONGENITAL ADRENAL HYPERPLASIA DUE TO DEFICIENT CHOLESTEROL SIDE‐CHAIN CLEAVAGE ACTIVITY (20, 22‐DESMOLASE) IN A PATIENT TREATED FOR 18 YEARS
Authors: HAUFFA B. P. , MILLER W. L. , GRUMBACH M. M. , CONTE F. A. , KAPLAN SELNA L. 
Published: March 2008

SUMMARYTwo siblings, a 9‐week‐old female and an 18‐year‐old male pseudohermaphrodite are described with deficient cholesterol side‐chain cleavage activity. The female died untreated in 1954; the second sibling, a phenotypically female infant with 46 XY karyotype, was diagnosed at age 5 weeks. Massive adrenal hyperplasia was revealed by intravenous pyelography showing downward displacement of the kidneys. Secretion rates of cortisol, aldosterone, deoxycor‐ticosterone and corticosterone were unmeasurable. Urinary 17‐hydroxycorti‐costeroids (17‐OHCS), tetrahydrocortisol, 17‐ketosteroids (17‐KS), pregnanetriol, pregnanediol, and Δ5‐3β‐ol steroids were not detected during prolonged administration of ACTH. Plasma concentrations and urinary excretion of gonadotrophins were increased. Gonadal mitochondria did not convert radioloabelled cholesterol to pregnenolone. The gluccocorticoid and mineralo‐corticoid deficiencies have been controlled well by steroid replacement therapy. Plasma ACTH concentrations and plasma renin activity remained strikingly elevated even when supraphysiologic doses of glucocorticoids and mineralocor‐ticoids were given. Oestrogen replacement alone induced a pubertal growth spurt. The differential diagnosis, the effects of long‐term steroid replacement therapy, and comparison with previously reported findings are discussed.
DIETARY INTAKE IN THYROTOXICOSIS BEFORE AND AFTER ADEQUATE CARBIMAZOLE THERAPY; THE IMPACT OF DIETARY ADVICE
Authors: ALTON S. , O'MALLEY B. P. 
Published: March 2008

SUMMARYDietary intake, including actual nutrient and energy intake, was assessed in 21 successive thyrotoxic patients before and after adequate carbimazole therapy. Group A (10 subjects) received regular formal dietary advice whereas Group B (11 subjects) did not. An age and sex matched control group, comprising 23 normal individuals, was also studied. The mean energy intake of all the thyrotoxic subjects was significantly greater than that of the normal control group (P < 0·0025). There was a greater overall reduction in the energy intake of Group A as compared with Group B (P < 0·01) and the former gained less weight, when expressed as a percentage of pretreatment weight. The mean final weight of all the thyrotoxic subjects exceeded the mean ideal weight for the group, reflecting a degree of true obesity at this stage. The simple measure of incorporating dietary advice into the treatment programme of thyrotoxic patients will usually result in some reduction of energy intake, and thus weight gain, en route to euthyroidism.
THE RESPONSE OF OBESE SUBJECTS TO CONTINUOUS INFUSION OF HUMAN PANCREATIC GROWTH HORMONE‐RELEASING FACTOR 1–44
Authors: DAVIES R. R. , TURNER S. J. , COOK D. , ALBERTI K. G. M. M. , JOHNSTON D. G. 
Published: March 2008

SUMMARYThe growth hormone (GH) response of seven obese subjects to a 4 h continuous infusion of human pancreatic GH‐releasing factor, 0·3 μg/kg/h, has been compared with that obtained in seven sex and age matched controls. The pattern of response was normal in the obese but peak GH levels (mean ± SEM: 13·8 ± 1·9 compared to 30·9 ± 4·7 mU/l, P < 0·01) and integrated GH levels (mean ± SEM: 27·1 ± 3·6 compared to 62·0 ± 9·7 mU/l/h, P < 0·01) were reduced in obese subjects. There was a negative correlation between the integrated GH response and the percentage ideal body weight (r=−0·80, P < 0·05), but no significant correlation with somatomedin‐C levels (r=+ 0·72; P= 0·07). Obese subjects have an impaired GH response to infusion of GH‐releasing factor which is not related to negative feedback by somatomedins.
SELECTIVE α2RECEPTOR BLOCKADE FACILITATES THE INSULIN RESPONSE TO ADRENALINE BUT NOT TO GLUCOSE IN MAN
Authors: STRUTHERS A. D. , BROWN D. C. , BROWN M. J. , SCHUMER B. , BLOOM S. R. 
Published: March 2008

SUMMARYThe adrenergic nervous system plays an important role in the control of insulin release and animal work suggests that this is mediated by way of α2adrenoceptors. A specific α2adrenoceptor antagonist (idazoxan) is now available for use in man and we have studied its effects on insulin release in normal volunteers (a) during the infusion of adrenaline (0·05 μg/kg/min) and (b) after an intravenous dose of glucose (20 g). The infusion of adrenaline alone had no significant effect on insulin release while in the presence of idazoxan, insulin release was markedly stimulated by adrenaline. Despite this, adrenaline‐induced hyperglycaemia was unaffected by pretreatment with idazoxan. In the second study, pretreatment with either idazoxan or a specific α1antagonist (prazosin) had no significant effect on either glucose tolerance, glucose‐induced insulin release or glucose‐induced suppression of glucagon. Intravenous glucose also had no significant effect on pancreatic polypeptide levels. Therefore the effect of adrenaline on insulin release is mediated by way of inhibitory α2adrenoceptors in the pancreas, while the release of insulin in response to glucose in a resting subject is independent of the α‐adrenergic system.
AUGMENTATION OF ANDROGEN‐RECEPTOR BINDING IN VITRO: STUDIES IN NORMALS AND PATIENTS WITH ANDROGEN INSENSITIVITY
Authors: EVANS B. A. J. , HUGHES I. A. 
Published: March 2008

SUMMARYUsing a simple whole‐cell binding assay, the effect of androgens on receptor binding activity was studied in genital skin fibroblasts (GSF) from normals and patients with either androgen insensitivity syndrome (AIS), isolated micropenis or hypospadias. Expressing the response as a ratio of augmented to basal specific dihydrotestosterone (DHT) binding, there was a 2.4±0.87 (mean±SD) increase following 20 h incubation with 2 nmol/1 [3H] ‐DHT in normal GSF. Mibolerone, a synthetic nonmetabolizable androgen, produced a similar response. Augmentation was temperature dependent, independent of androgen metabolism and suppressed by protein and RNA inhibitors. All patients with isolated micropenis and hypospadias demonstrated normal augmentation of receptor binding activity. There was no response in patients with complete AIS who were receptor negative. In the majority of patients with partial AIS, there was an in vitro response to androgens; those reared as males all virilized with androgen therapy. In contrast, a male patient with partial AIS who failed to respond to high‐dose androgen therapy, showed no augmentation of specific androgen binding in GSF preincubated with androgens. This technique may be a useful in vitro bioassay to predict androgen responsiveness in vivo in patients with androgen insensitivity, either soon after birth in the short‐term, or later at puberty.
ACCURATE LOCALIZATION OF INSULINOMA USING PERCUTANEOUS TRANSHEPATIC PORTAL VENOUS SAMPLING—USEFULNESS OF SIMULTANEOUS MEASUREMENT OF PLASMA INSULIN AND GLUCAGON LEVELS
Authors: KINOSHITA Y. , NONAKA H. , SUZUKI S. , KONDO T. , CHIHARA K. , CHIBA T. , FUJITA T. , KOTOURA Y. , YAMAMURA T. 
Published: March 2008

SUMMARYBy means of percutaneous transhepatic portal venous sampling (PTVS), plasma insulin and glucagon levels were determined simultaneously at various sites of the hepatic portal venous system in two patients with insulinoma and four patients without. In the two cases of insulinoma, an obvious rise of insulin concentration was observed at the vicinity of the tumour, while glucagon levels were not elevated in the blood samples showing an insulin peak. In the remaining four cases without evidence of insulinoma, significant step‐ups of plasma insulin occurred in the splenic vein as well, but were accompanied with concomitant elevation of plasma glucagon levels in the same blood samples. Thus, by measuring insulin alone, false positive data may frequently be obtained when PTVS is performed on patients with suspected insulinomas. The simultaneous measurement of insulin and glucagon might be helpful in avoiding such errors.
CLINICAL AND ENDOCRINE STUDIES ON PATIENTS WITH AMENORRHOEA ASSOCIATED WITH WEIGHT LOSS
Authors: NAKAMURA Y. , YOSHIMURA Y. , ODA T. , KATAYAMA E. , KAMEI K. , TANABE K. , IIZUKA R. 
Published: March 2008

SUMMARYTwo hundred and forty‐three patients with amenorrhoea associated with weight loss were studied. At the onset of amenorrhoea, regardless of percentage weight loss, basal levels of LH were low and LH responses to LHRH were impaired. However, both basal and stimulated levels of FSH were comparable to normal. With resumption of menstruation, the basal and stimulated levels of LH were found to rise to normal, while FSH responses continued to exceed normal. However, 16·6% of 66 unimproved cases had normal responses but remained amenorrhoeic. Furthermore, amenorrhoea persisted in 71% of 31 patients with complete recovery of body weight. No significant correlation was noted between percentage weight loss and responsiveness to LHRH, nor between recovery of body weight and resumption of menstruation. Return to normal weight is desirable for resumption of normal cyclic menstruation and hypothalamic‐pituitary function, but is not always effective.
FAILURE OF HIGH‐DOSE SUSTAINED RELEASE LUTEINIZING HORMONE RELEASING HORMONE AGONIST (BUSERELIN) PLUS ORAL TESTOSTERONE TO SUPPRESS MALE FERTILITY
Authors: MICHEL E. , BENTS H. , AKHTAR FATIMA BINT , HÖNIGL W. , KNUTH U. A. , SANDOW J. , NIESCHLAG E. 
Published: March 2008

SUMMARYPreviously we have demonstrated that sperm counts of normal young men decreased during constant subcutaneous infusion of the LHRH agonist buserelin (118 or 230 μg/d). In order to test whether azoospermia can be achieved with higher doses, seven young men received 450 μg buserelin subcutaneously daily for 12 weeks via extracorporeal osmotic minipumps. To avoid symptoms of androgen deficiency, oral supplementation with 80 mg/d testosterone undecanoate (TU) was initiated in week 5 and was increased to 120 mg/d by week 8. Follow‐up after treatment lasted for another 12 weeks. In order to evaluate possible psychotropic effects of treatment‐related endocrine changes, continuous psychometric testing was performed focusing on personality, emotions and sexuality. After an initial rise, both serum LH and FSH returned to normal. FSH was below normal during the 3rd–5th week following treatment. LHRH stimulation tests performed at the end of treatment showed pituitary desensitization. Serum T (always measured between 0800 and 1300 h at least 12 h after last TU) tended to decrease by week 7 and remained slightly depressed until the end of treatment while libido, potency and emotional well‐being remained unchanged. While testicular volumes showed a reduction from week 7 of treatment to week 10 post‐treatment, sperm counts decreased only insignificantly from 65 ± 10 to 44 ± 14 million per ml in week 12 post‐treatment. Severe oligo‐ or azoospermia was not observed in any of the seven men. It is concluded that full androgen substitution by TU can drastically delay if not abolish the antifertility effect of LHRH‐induced pituitary desensitization.
EFFECTS OF LH SUPPRESSION IN POLYCYSTIC OVARY SYNDROME
Authors: FLEMING R. , BLACK W. P. , COUTTS J. R. T. 
Published: March 2008

SUMMARYA LH‐releasing hormone (LHRH) analogue was administered to subjects with elevated circulating LH concentrations and elevated androgens (polycystic ovary syndrome, PCO) and also to a control group with normal menstrual rhythm and normal LH and androgens. In both groups circulating LH concentrations were reduced to low and indistinguishable concentrations. Oestradiol, oestrone, androstenedione and testosterone levels were all reduced by treatment in both groups. However, the reduction in androgen concentrations was less marked in the patients with PCO. The oestrogen/androgen ratios remained relatively unaltered, but the testosterone levels remained slightly elevated in the PCO patients after treatment. The results suggest that patients with PCO syndrome show a disorder of androgen metabolism independent of elevated LH concentrations.
PREDICTION OF RESPONSE TO ENDOCRINE THERAPY IN PRONOUNCED CYCLICAL MASTALGIA USING DYNAMIC TESTS OF PROLACTIN RELEASE
Authors: KUMAR S. , MANSEL R. E. , HUGHES L. E. , EDWARDS C. A. , SCANLON M. F. 
Published: March 2008

SUMMARYMany of the endocrine agents currently used to treat symptomatic benign breast disease modify the action or secretion of prolactin. We have compared the responses to hormonal therapy with dynamic assessment of prolactin control in 29 patients with cyclical mastalgia and in 7 patients with non‐cyclical mastalgia. The tests of prolactin release used were direct stimulation by TRH or dopaminergic blockade by domperidone. These were carried out before treatment in the mastalgic patients and also in 22 age‐matched asymptomatic controls. The response to treatment was assessed using a special pain chart and visual linear analogue scale. Patients with cyclical mastalgia could be divided into two groups: those in whom the peak prolactin release was exaggerated (>4000 mU/1) and those in whom the prolactin release was less marked and similar to control subjects and patients with non‐cyclical mastalgia. Patients in the cyclical mastalgia group with a high peak prolactin release responded to hormonal treatment significantly more frequently (90%) than those with a normal prolactin release (50%). Basal prolactin levels did not correlate with the response to treatment. In the non‐cyclical mastalgia group, no patient had peak prolactin release >4000 mU/1 and none responded to therapy. This study indicates that dynamic tests of prolactin release in cyclical mastalgia may be useful in predicting the subsequent satisfactory response to endocrine therapy if a high peak prolactin release is induced.
HYPERTHYROIDISM AND THE IMPALPABLE THYROID GLAND
Authors: GREENWOOD R. M. , DALY J. G. , HIMSWORTH R. L. 
Published: March 2008

SUMMARYA retrospective analysis of 594 unselected cases of hyperthyroidism from one district was made to determine whether the thyroid gland had been palpable on presentation. The thyroid had been diffusely palpable in 374 patients (63%), nodular in 110(19%) and impalpable in 96 (16%); there was no clinical record in 14 (2%) cases. Under 40 years of age a diffuse gland was usual, being present in 86% of cases. The proportion of nodular and impalpable glands both increased progressively with age comprising 30% and 48% respectively in patients older than 70 years. Graves's ophthalmopathy was present in 13% of hyperthyroid patients with diffuse glands, in 12% of those with impalpable glands, but in only 1·5% of those with nodular thyroids. Thyroid autoantibodies were found with a similar frequency in all three groups. There was a very good correspondence between clinical assessment of shape and nodularity of thyroid and the results of isotope scanning; the majority of patients with impalpable glands (86%) had a diffuse uptake of isotope. In the elderly hyperthyroid patient an impalpable thyroid gland is common and is not a factor to weigh against the diagnosis.
INFLUENCE OF ENDOGENOUS AND EXOGENOUS OESTROGENS ON POSTERIOR PITUITARY SECRETION IN WOMEN
Authors: WILLIAMS T. D. M. , EDWARDS A. , FAIRHALL K. M. , ROBINSON I. C. A. F. , McGARRICK G. M. , LIGHTMAN S. L. 
Published: March 2008

SUMMARYFour normally mestruating subjects were studied throughout the menstrual cycle to investigate changes in plasma LH, arginine vasopressin (AVP), oxytocin (OT) and oxytocin associated neurophysin (NPOT). A clear mid‐cycle LH peak was observed in each subject. Mean levels of AVP, OT and NPOT were 2·2 pmol/1, 1·1 pmol/1 and 39 pmol/1, respectively. There were no significant differences between plasma levels during follicular, mid‐cycle and luteal phases for each of these. Two further subjects with anovulatory cycles were studied in a similar way. In the first subject, with polycystic ovarian disease, posterior pituitary peptide levels were in the normal range, whereas the other subject, recovering from anorexia nervosa, had raised plasma levels of all posterior pituitary peptides (AVP 8·1 pmol/1, OT 1·8 pmol/1, NPOT 131 pmol/1, mean values) despite a normal osmolality. Administration of ethinyl oestradiol, 100 μg or 500 μg, had no effect of either AVP or OT, but 100 μg caused a marked rise in NPOT levels in all cases within 12 h (from mean 64 pmol/1 to mean 196 pmol/1) and the levels remained elevated for 3 d.
ESTIMATION OF 1,25 DIHYDROXYVITAMIN D BY CYTORECEPTOR AND COMPETITIVE PROTEIN BINDING ASSAYS WITHOUT HIGH PRESSURE LIQUID CHROMATOGRAPHY
Authors: NICHOLSON G. C. , KENT J. C. , GUTTERIDGE D. H. , RETALLACK R. W. 
Published: March 2008

SUMMARYUsing two different cultured rat osteosarcoma cell lines (UMR 106 and ROS 17/2·8) we have investigated the recently described cytoreceptor assay for 1,25‐dihydroxyvitamin D (1,25‐(OH)2D). The assay method is relatively simple and sensitive to 2·4 fmole per tube. Using either cell line, assay of serum samples, whose only preparation consisted of extraction and purification on a disposable diatomaceous earth column, produced variable values for serum 1,25‐(OH)2D. Additional purification, using a disposable silicic acid minicolumn to remove other vitamin D metabolites resulted in consistent values and additional HPLC resulted in no further decrease in the values obtained. Our results show that a single two stage non‐HPLC column can purify serum samples for assay in the cytoreceptor assay. The method is also applicable to the competitive protein binding assay employing calf thymus cytosol and the correlation between values obtained by both methods is highly significant. It is a sensitive, simple, and accurate method with technical advantages which allow greater sample throughput than other 1,25‐(OH)2D assays.