bluuebunny/crossref_metadata_2025_split huggingface dataset:
EFFECTS OF THE GABAERGIC AGENT SODIUM VALPROATE ON THE ARGININE VASOPRESSIN RESPONSES TO HYPERTONIC STIMULATION AND UPRIGHT POSTURE IN MAN
Authors: CHIODERA P. , GNUDI A. , VOLPI R. , MARCHESI C. , MARCHESI M. , DAVOLI D. , CAPRETTI L. , COIRO V. 
Published: March 2008

SUMMARYIn order to evaluate the possible influence of GABAergic neurotransmission on the arginine vasopressin (AVP) response to osmotic and pressure volumetric stimuli, the GABAergic drug sodium valproate was administered by mouth (200 or 400 mg 16 h, 8 h and just before tests) to eight normal men before osmotic (i.v. infusion of 0.51 m NaCl for 2 h) and orthostatic (standing upright and maintaining an orthostatic position for 20 min) tests. In both experimental conditions, the AVP rise was significantly lower in the presence than in absence of sodium valproate. The maximum AVP responses in the control orthostatic and osmotic tests were respectively 2.3 and 2.5 times higher than basal levels. When 600 mg sodium valproate was given, the maximum AVP rise in response to hypovolaemic and osmotic stimuli were respectively 1.75 and 2.1 times higher than basal value. Similar results were obtained giving 1.2 g sodium valproate. These results suggest that in man a GABAergic pathway is involved in the AVP responses to hypovolaemic and hyperosmotic stimuli.
URINARY GROWTH HORMONE DURING PUBERTY IN NORMAL AND DIABETIC CHILDREN
Authors: EDGE J. A. , HOURD P. , EDWARDS R. , DUNGER D. B. 
Published: March 2008

SUMMARYThe measurement of GH in urine may have many clinical applications, particularly in childhood. We have used a highly sensitive direct immunoradiometric assay to examine urinary GH excretion in children during puberty.Fifty‐five healthy schoolchildren collected timed overnight urine samples. A further 36 children (15 normal, six of short stature and 15 diabetic) collected urine samples during a total of 50 ovenight plasma GH secretory profiles (15‐min sampling).Overnight urinary GH excretion increased during puberty, with a peak at breast stage 2 in girls, and genital stage 4 in boys, before declining at stage 5. There was a positive correlation (r = 0.57, p = 0.003) with height velocity in girls, but not in boys. At each puberty stage except 2, the diabetics excreted more urinary GH than the normal children.There was a highly significant correlation (r= 0.79, p<50.001) between mean overnight plasma GH concentrations and urinary GH excretion, suggesting that the latter accurately reflects physiological GH secretion.
CIRCULATING MONOCYTE (MACROPHAGE)‐SPECIFIC ANTIBODIES IN PATIENTS WITH AUTOIMMUNE THYROID DISEASES
Authors: ZEKI K. , SHIRAKAWA F. , FUJIHIRA T. , KANATANI M. , WATANABE K. , SUZUKI H. , ETO S. 
Published: March 2008

SUMMARYWe investigated the presence of circulating monocyte‐specific antibodies (monocytotoxic activities) by a complement‐dependent cytotoxicity test and the relations between these monocytotoxic activities and other immunological indices in patients with autoimmune thyroid diseases. Antibodies reactive for monocytes (macrophages) were found in the sera from patients with autoimmune thyroid diseases. These antibodies were present in both IgG and IgM fractions and specific for monocytes since they were absorbed by monocytes but not by lymphocytes or granulocytes; furthermore, lymphocytotoxic and granulocytotoxic activities were not changed after the absorption of the sample sera by monocytes. Also, these antibodies did not have cross‐reactivity to thyroid‐specific antigens demonstrated by absorption tests and their specificity was different from anti HLA‐DR antibody demonstrated by a flow cytofluorometric analysis. Monocyte‐specific antibodies are reactive for autologous monocytes as well as allogenic monocytes. Patients who had positive monocytotoxic activities had high levels of TSH receptor antibodies (TRAb) and antimicrosomal antibodies in Graves’disease, and monocytotoxic activities were significantly correlated with the levels of TRAb in Graves’disease. These results suggest that the monocyte‐specific antibodies (monocytotoxic activities) were significantly correlated with the immunological activities in Graves’disease.
CORRECTION OF LOW CIRCULATING LEVELS OF 1,25‐DIHYDROXYVITAMIN D BY 25‐HYDROXYVITAMIN D DURING REVERSAL OF HYPOMAGNESAEMIA
Authors: FUSS M. , BERGMANN P. , BERGANS A. , BAGON J. , COGAN E. , PEPERSACK T. , VAN GOSSUM M. , CORVILAIN J. 
Published: March 2008

SUMMARYThe effect of 25‐hydroxyvitamin D (250HD), given orally during the reversal of hypomagnesaemia, was studied in five patients with hypomagnesaemic hypocalcaemia and low serum levels of 25OHD and 1,25‐dihydroxyvitamin D (1,25(OH)2D). The results were compared to those obtained in five other patients with similar initial levels of magnesium, calcium, 25OHD and 1,25(OH)2D who did not receive 25OHD. Serum levels of 1,25(OH)2D in the ten hypomagnesaemic patients were lower than in ten control subjects with low serum levels of 25OHD. The reversal of hypomagnesaemia was similar in the two groups of patients and elicited a similar increase of circulating iPTH levels. The expected increase of circulating 25OHD was observed in patients supplemented with 25OHD; their circulating 1,25(OH)2D rose within 48 h to normal levels, contrasting with the delayed and poor increase of 1,25(OH)2D in patients receiving no 25OHD. The evolution of serum calcium was however identical in the two groups. Our results suggest that vitamin D deficiency was a significant factor leading to low circulating levels of 1,25(OH)2D in hypomagnesaemic hypocalcaemic patients. The biological consequences of low serum 1,25(OH)2D in these patients remain unclear, but clearly, normal levels of 1,25(OH)2D are not essential for the correction of hypomagnesaemic hypocalcaemia.
STUDIES OF TWO THYROTROPHIN‐SECRETING PITUITARY ADENOMAS: EVIDENCE FOR DOPAMINE RECEPTOR DEFICIENCY
Authors: BEVAN J. S. , BURKE C. W. , ESIRI M. M. , ADAMS C. B. T. , BALLABIO M. , NISSIM M. , FAGLIA G. 
Published: March 2008

SUMMARYOf 22 previously reported patients with TSH‐secreting pituitary adenomas challenged with dopamine agonists, 18 showed no decrease in serum TSH. There have been few in‐vitro studies of these rare tumours so the mechanism of the dopaminergic resistance has remained obscure. We describe two further patients with thyrotrophinomas; the first was thyrotoxic (T3 6.1 nmol/l, TSH 7 mU/l) and the second was diagnosed after radioiodine for presumed Graves’disease. The second patient had an α‐subunit: TSH molar ratio less than unity (0.27). In‐vivo TSH responses to TRH, bromocriptine and domperidone were compared with those of the resected tumour cells in vitro, the latter studied using a continuous perifusion system. Dopamine receptors were sought in membranes from each tumour using a radioreceptor assay employing 3H‐spiperone. Patient 1 showed significant increases in serum TSH (7 to 13 mU/l) and α‐subunit (18.7 to 385 ng/ml) after 200 μg TRH (i.v.) but patient 2 showed no such increases (TSH: 69 to 72 mU/l, α‐subunit: 4.9 to 5.2 ng/ml). Neither patient showed a change in serum TSH following bromocriptine 2.5 mg (orally) or domperidone 10 mg (i.v.), though serum PRL responded normally. Serum TSH from patient 1 was of apparently normal molecular size but increased bioactivity (B/I ratio 3.8) and that from patient 2 was of increased molecular size but reduced bioactivity (B/I ratio 0.1). Tumour cells from each patient immunostained for TSHβ and α‐subunit, and secreted TSH in vitro. The first showed dose‐dependent TSH release after TRH (1–100 ng/ml) which could not be inhibited by dopamine (5 μmol/l) but the second was unresponsive to TRH in vitro. Neither tumour showed inhibition of TSH release by dopamine (5 μmol/l) or bromocriptine (0.01–10 nmol/l) and neither contained membrane‐bound dopamine receptors. The results suggest that the dopaminergic resistance typical of most TSH‐secreting pituitary adenomas may be due to altered or absent membrane‐bound dopamine receptors.
URINARY EXCRETION OF HUMAN EPIDERMAL GROWTH FACTOR IN THE VARIOUS STAGES OF DIABETIC NEPHROPATHY
Authors: DAGOGO‐JACK S. , MARSHALL S. M. , KENDALL‐TAYLOR P. , ALBERTI K. G. M. M. 
Published: March 2008

SUMMARYEpidermal growth factor (EGF) is a polypeptide mitogen first isolated from mouse submaxillary glands and later from human urine. We have examined the pattern of urinary excretion of human EGF (hEGF) in normal subjects and in diabetic patients with varying degrees of nephropathy. hEGF was measured by homologous radioimmunoassay and expressed in terms of urinary creatinine excretion. On the basis of their albumin excretion rate, the diabetic patients were divided into those with normoalbuminuria (albumin excretion rate 3.5 (1.4–9.8) μg/min; mean (range)), microalbuminuria (albumin excretion rate 75 (30–128) μg/min) and macroalbuminuria (289 (169–879) μg/min). The albumin excretion rate for the normal subjects was 3.7 (1.6–9.7) μg/min. The mean (range) hEGF excretion (nmol hEGF/mmol creatinine) was 0.69 (0.47–1.29) for 19 healthy subjects, 0.60 (0.16–1.36) for the normoalbuminuric group (n= 18; NS), 0.47 (0.10–0.83) for the microalbuminuric patients (n = 19; P < 0.001 vs controls and normoalbuminuric diabetics) and 0.38 (0.10–0.63) for the macroalbuminuric group (n=18; P < 0.001 vs controls and normoalbuminuric diabetics). There was an inverse correlation between albumin excretion rate and hEGF: creatinine ratio (r =−0.49; P= 0.02). These results show a progressive decline in hEGF excretion in diabetic patients with varying degrees of nephropathy and do not support the hypothesis that increased kidney size seen in early nephropathy is due to excessive amounts of EGF in the urine.
ACUTE DEXAMETHASONE SUPPRESSION OF ACTH SECRETION STIMULATED BY HUMAN CORTICOTROPHIN RELEASING HORMONE, AVP AND HYPOGLYCAEMIA
Authors: HOHNLOSER J. , VON WERDER K. , MÜLLER O. A. 
Published: March 2008

SUMMARYIn order to obtain more insight into the mechanisms regulating endogenous ACTH secretion in humans we studied the inhibitory effect of acute i.v. dexamethasone administration on ACTH release under various conditions. Six male volunteers were subjected to six different protocols. After combined i. v. injection of 100 μg corticotrophin releasing hormone (CRH) and 100 μg growth hormone releasing hormone (GRH) there was the expected rise in ACTH (area under the curve, 1053 ± 204 (SE) (pmol/l) min) and cortisol (59788 ± 10098 (nmol/l) min) rise which was suppressed by prior i. v. injection of 2 mg dexamethasone (ACTH: 444 ± 63 (pmol/l) min; cortisol: 28528 ± 2152 (nmol/l) min). Insulin hypoglycaemia (IH) led to a more pronounced ACTH and cortisol rise compared with CRH (6307 ± 817 (pmol/l) min and 82080 ± 21934 (nmol/l) min, respectively) which was not completely suppressed by prior pretreatment with dexamethasone (ACTH, 580 ± 103 (pmol/l) min; cortisol: 55649 ± 5821 (nmol/l) min). Combined AVP/CRH injection (10 IU/100 fig) after pretreatment with dexamethasone (344 ± 41 (pmol/l) min for ACTH; 32832 ± 3173 (nmol/l) min for cortisol) could not reproduce the ACTH secretion following IH after pretreatment with dexamethasone (579 ± 103 (pmol/l) min for ACTH and 55649 ± 5821 (nmol/l) min for cortisol). In all subjects a saline control with 2 mg dexamethasone was performed. These findings confirm the acute inhibitory effect of glucocorticoids on CRH‐stimulated ACTH secretion. Since CRH‐induced ACTH secretion is almost completely abolished by administration of dexamethasone the ACTH rise following IH after dexamethasone can not be mediated by endogenous CRH alone. Moreover, since the addition of AVP to CRH (after dexamethasone suppression) could not reproduce the ACTH rise during IH after dexamethasone pretreatment, an additional, yet unknown factor stimulating ACTH secretion may be involved. In the same protocols, no significant difference could be observed comparing IH and GRH induced GH secretion (4948 ± 1172 (mU/l) min vs 3596 ± 820 (mU/l) min, NS); furthermore, in contrast to results obtained by chronic steroid administration, acute i. v. dexamethasone pretreatment did not affect IH or GRH‐induced GH secretion (4110 ± 666 (mU/l) min vs 2916 ± 462 (mU/l) min, NS). The GRH‐stimulated GH secretion (3596 ± 820 (mU/l) min) was not suppressed by prior intravenous treatment with dexamethasone (2916 ± 504 (mU/l) min, NS).
THE LONG‐TERM OUTCOME OF THYROIDECTOMY FOR SPORADIC NON‐TOXIC GOITRE
Authors: BERGHOUT A. , WIERSINGA W. M. , DREXHAGE H. A. , VAN TROTSENBURG P. , SMITS N. J. , VAN DER GAAG R. D. , TOUBER J. L. 
Published: March 2008

SUMMARYTo study the long‐term outcome after thyroidectomy, 113 sporadic non‐toxic goitre patients who underwent thyroidectomy in our hospital in the period 1974–1983, were studied. Five patients complained of recurrent goitre; a goitre was found on inspection and palpation in these five and in 15 others. There were no differences between the 20 patients with goitre and the 93 patients without goitre with regard to sex, age, duration of goitre, indication and type of thyroidectomy, postoperative thyroid hormone medication, period of follow‐up, and T4, T3, or TSH plasma values at the time of follow‐up examination. Twenty‐three patients complained of voice changes since thyroidectomy. In a case control study, included in this follow‐up study, 19 patients with goitre, i.e. thyroid size I and II as estimated by inspection and palpation (cases), and 16 patients without goitre, i.e. thyroid size OA and OB (controls), were studied in more detail. No difference between cases and controls was found in any of the above mentioned parameters that could explain the recurrence of goitre. Thyroid volume (median) was greater in the cases (34–1 ml, range 7.9–83.4) than in the controls (10.3 ml, range 2.5–48.7) (P < 0.001), although a considerable overlap between the two groups was observed. One or more thyroid nodules were found in 89.5% of the cases and in 62–5% of the controls (NS). Serum thyroid growth stimulating immunoglobulin (TGI) was present both in cases (68%) and controls (50%). TGI was present in high titres in all five patients who complained about recurrent goitre. Thyroid volume was negatively related to the plasma level of TSH (r =−0.36, P < 0.05), and positively but not significant to serum TGI. In conclusion: (1) a goitre is found in 17.7% of sporadic non‐toxic patients at long‐term follow‐up after thyroidectomy, not related to age, sex, duration of goitre, indication or type of operation, postoperative thyroid hormone medication, period of follow‐up, or plasma T3, T4, or TSH; (2) TGI is more prevalent in patients who complain of recurrent goitre after thyroidectomy; (3) thyroidal nodular disease persists in the majority of patients after thyroidectomy.
SERUM GROWTH HORMONE BINDING PROTEIN ACTIVITY IN HEALTHY NEONATES, CHILDREN AND YOUNG ADULTS: CORRELATION WITH AGE, HEIGHT AND WEIGHT
Authors: SILBERGELD A. , LAZAR L. , ERSTER B. , KERET R. , TEPPER R. , LARON Z. 
Published: March 2008

SUMMARYSerum growth hormone binding protein (GHBP) activity was estimated in healthy neonates (n=6), children and adolescents (n=97) and young adults (n=19). GHBP activity was measured by incubating 125I‐hGH (human growth hormone) (˜ 25 000 c. p. m.) with serum (100 μ1) in the presence and in the absence of excess unlabelled hGH, followed by separation of specifically bound 1251‐hGHBP complexes from free 125I‐hGH by gel filtration on Ultrogel AcA44 minicolumns. The results are expressed as the percentage specific binding relative to an adult reference serum (%RSB), after correction for endogenous hGH of the unknown serum. The between‐assay coefficients of variation for two sera of %RSB activity of 51.2 and 115.4% were 6.0 and 7.0% respectively. In neonates, low values of serum GHBP were found (%RSB = 27.1 ± 5.0 SEM) followed by a major rise during the first 6 years of life to a mean value (%RSB = 68.3 ± 4.1 SEM) which more than doubled that of neonates. Thereafter, values rose progressively throughout childhood and puberty to reach maximum values in young adults (%RSB =95.0 ± 3.1 SEM). A novel observation was that serum GHBP activity correlated significantly with height standard deviation score (SDS) (males: r= 0.77, P < 0.001; females: r= 0.56, P= 0.01) and weight SDS (P < 0.001) for both sexes before puberty. During puberty GHBP correlated only with weight SDS in males (r=0.60, P < 0.01). In all age groups studied, no correlation could be found between serum GHBP and height velocity.
MEGAVOLTAGE PITUITARY IRRADIATION IN THE MANAGEMENT OF CUSHING'S DISEASE AND NELSON'S SYNDROME: LONG‐TERM FOLLOW‐UP
Authors: HOWLETT T. A. , PLOWMAN P. N. , WASS J. A. H. , REES L. H. , JONES A. E. , BESSER G. M. 
Published: March 2008

SUMMARYWe report the long‐term follow‐up of the clinical and biochemical effects of megavoltage pituitary irradiation (radiotherapy; RT), administered as primary or secondary therapy, for pituitary Cushing's disease and Nelson's syndrome in 52 patients. Irradiation was administered, from a 4–15 MeV linear accelerator, via a three‐field technique (two lateral, one frontal), to a total dose of 4500 cGy (rad) in 25 fractions over 35 days. Twenty‐one patients received RT as primary ablative therapy for Cushing's disease and were under follow‐up 5.8 to 15.5 years later (median 9.5 years). All were initially treated with metyrapone to induce normal mean plasma cortisol levels, and all achieved clinical remission on this therapy. At latest follow‐up, 12 (57%) are off all therapy, in clinical remission, with a normal mean cortisol through the day; however, only two show completely normal plasma cortisol responses to dynamic testing; four remain on medical therapy with metyrapone or op'DDD and all have required a steady dose reduction accompanied by falling plasma ACTH levels; five have required alternative therapy with bilateral adrenalectomy and/or transsphenoidal hypophysectomy. Fifteen patients received RT for Nelson's syndrome, developing after bilateral adrenalectomy, and have been followed up for 1.5 to 17.3 years (median 9–6 years). Fourteen patients showed progressive de‐pigmentation, shrinkage of the pituitary adenoma and fall in plasma ACTH levels to 1–72% (median 16%) of the pre‐RT basal value. In the remaining patient an initial fall in plasma ACTH was followed by tumour enlargement at 6 years, leading to death at 11 years after RT. Of the remaining patients, results are assessed in nine who received RT after unsuccessful transsphenoidal surgery, three after transfrontal surgery for aggressive macroadenomas, and four prophylactically after bilateral adrenalectomy. Radiotherapy remains a valuable second‐line therapy for Cushing's disease and its complications.
TAMOXIFEN PROLONGS LUTEAL PHASE IN PREMENOPAUSAL WOMEN BUT HAS NO EFFECT ON THE SIZE OF UTERINE FIBROIDS
Authors: LUMSDEN M. A. , WEST C. P. , BAIRD D. T. 
Published: March 2008

SUMMARYTamoxifen (20 mg per day) was administered for at least 3 months to six premenopausal women with uterine fibromyomata. In all the women there was an increased variability in the length of the menstrual and ovarian cycle associated with a significant lengthening of the luteal phase (16.9 ± 3.5 vs 12.5 ± 1.5 days, mean ± SD, P < 0.02). The concentration of oestradiol and progesterone in plasma and their metabolites in urine (oestrone glucuronide and pregnanediol) increased reflecting multiple follicular development and ovulation. There was a significant rise in the concentration of FSH during the luteal phase of the cycle (8.0 ± 2.9 vs 2.0 ± 1.7 U/I, P < 0.01). There was no change in the size of the uterine leiomyomata. These results demonstrate that the antioestrogen tamoxifen results in an increased secretion of gonadotrophins by antagonizing the effects of oestradiol at the hypothalamus and anterior pituitary. The lengthening of the luteal phase suggests oestradiol may play a role in the mechanism of luteal regression either locally or via feedback effect on gonadotrophins.
AN ATTEMPT TO ALTER THE PATHOPHYSIOLOGY OF POLYCYSTIC OVARY SYNDROME USING A GONADOTROPHIN HORMONE RELEASING HORMONE AGONIST—NAFARELIN
Authors: WILLIAMS IOLA A. , SHAW ROBERT W. , BURFORD GRAHAM 
Published: March 2008

SUMMARYThe aim of this study was to see whether the pathophysiology of polycystic ovary syndrome could be altered by suppressing the abnormal cycle of events associated with abnormal gonadotrophins and androgens. Fifteen women with polycystic ovary syndrome were treated with the GnRH agonist Nafarelin at a dosage of 200 μg twice daily intranasally for a period of 3 or 6 months. Eight of these women also had a dexamethasone suppression test 0.5 mg four times daily for 48 h before and after treatment with Nafarelin, in order to differentiate between an adrenal and ovarian source for the excess androgens. Gonadotrophins and androgens were well suppressed, LH to a mean of 1.5 IU/1, testosterone to 1.1 nmol/1 and androstenedione to 6.4 nmol/1. Three months after discontinuing Nafarelin, all these hormones had returned to pretreatment levels. The ultrasound appearance of the ovaries showed no consistent reduction in ovarian volume or the disappearance of ovarian follicles. Hirsutism showed slight improvement in four out of seven patients. After treatment one patient out of the eight complaining of infertility, conceived spontaneously and one patient ovulated on a reduced dosage of clomiphene. There was no change in the menstrual pattern of the others. Despite the achievement of good hormonal suppression, there was no change in the condition after therapy was discontinued suggesting that whatever the cause of the condition it remains a permanent situation.
PITUITARY FUNCTION IN ISOLATED GONADOTROPHIN DEFICIENCY
Authors: YEH JOHN , REBAR ROBERT W. , LIU JAMES H. , YEN SAMUEL S. C. 
Published: March 2008

SUMMARYHypothalamic‐pituitary function was assessed in 24 individuals with isolated gonadotrophin deficiency (IGD). Thirteen had normal olfaction (Group I) while 11 (Group II) had anosmia (Kallmann's syndrome). In response to a 10 pg intravenous (i.v.) bolus of GnRH, the minimal dose required to evoke a consistent gonadotrophin response in normal subjects, the patients responded with significant LH and FSH increases over baseline (P < 0.01). In Group II patients, large doses (150 μg) of GnRH, which elicit maximal release of gonadotrophin in normal subjects did not increase gonadotrophin release beyond that produced by a 10 μg bolus. In response to two 10 μg GnRH doses, at times 0 and 120 min, the IGD patients responded with similar LH increases to both boluses (both P < 0.01 compared to baseline). The maximal PRL responses to arginine infusion and to TRH in the male patients were similar to those of normal males. However, in the IGD females, the PRL response to TRH was less than in normal females. The TSH responses to TRH in IGD males and females were similar to each other and similar to normal. The IGD male GH response to arginine infusion was comparable to that in normal males. We conclude that (1) IGD patients appear to retain minimal endogenous GnRH secretion so that the IGD pituitary responds to a minimal dose of GnRH without priming; (2) IGD is a heterogeneous syndrome in which affected individuals with and without normal olfaction represent parts of the spectrum of the same disease; and (3) except for the PRL response in females, the PRL, TSH and GH responses demonstrate that the IGD pituitaries are largely intact.