bluuebunny/crossref_metadata_2025_split huggingface dataset:
DETERMINATION OF THE FREQUENCY OF PULSATILE LUTEINIZING HORMONE SECRETION BY TIME SERIES ANALYSIS
Authors: MURDOCH A. P. , DIGGLE P. J. , DUNLOP W. , KENDALL‐TAYLOR P. 
Published: March 2008

SUMMARYStatistical methods of time series analysis, in particular, spectral analysis, have been used to determine the pulse frequency of LH secretion. This method can detect significant harmonic variation within the data. Six normal women in the early follicular phase of the menstrual cycle were studied at 5 and 15 min sampling intervals and significant dominant pulse frequencies were revealed in five subjects (51–120 min). In addition, a low frequency variation (>6 h) was revealed in four subjects and more rapid frequencies (20 and 13.3 min) were seen clearly in one subject. Comparison of repeat studies on four individuals at the same stage of different menstrual cycles and on two individuals in the same cycle failed to demonstrate differences in five of the six subjects. This method of analysis offers a new approach to the analysis of LH pulse frequency. Realistic comparisons of this frequency between and within individuals can now be made. A new observation of superimposed harmonic components of LH pulsatility has also been recorded.
DEVELOPMENT AND APPLICATION OF A MID‐REGION SPECIFIC ASSAY FOR HUMAN PARATHYROID HORMONE
Authors: GLEED J. H. , HENDY G. N. , NUSSBAUM S. R. , ROSENBLATT M. , O'RIORDAN J. L. H. 
Published: March 2008

SUMMARYA new peptide spanning residues 28–54 of human parathyroid hormone (PTH) was synthesized and used to develop a homologous immunoradiometric assay specific for the mid‐region of human PTH. The peptide was coupled to cellulose and used to adsorb mid‐region antibodies from a goat antiserum against intact human PTH. This assay has been applied to the measurement of circulating PTH in man: in normal subjects the concentration in serum ranged from undetectable (> 40 pg/ml) to 70 pg/ml, the reference standard being the human PTH 28–54 peptide. In patients with primary hyperparathyroidism concentrations ranged from 120 to 1800 pg/ml. Hormone was not detected in patients with hypoparathyroidism. In normal subjects and in patients with primary hyperparathyroidism the mid‐region PTH concentrations were similar to those obtained in an aminoterminal specific assay. By contrast, carboxy‐terminal PTH concentrations were markedly higher being 10‐fold greater in both groups studied. In patients with primary hyperparathyroidism undergoing parathyroidectomy and in chronic renal failure patients who were infused with calcium, mid‐region and aminoterminal PTH disappeared much more rapidly than carboxy‐terminal PTH. However, although mid‐region PTH was initially cleared as quickly as aminoterminal PTH, it then reached a plateau and remained at a higher level. Thus the mid‐region specific assay described here is proving to be of value in the study of the secretion and metabolism of PTH.
DEVELOPMENT OF A CYTOCHEMICAL ASSAY FOR PLASMA VASOPRESSIN: APPLICATION TO STUDIES ON WATER LOADING NORMAL MAN
Authors: BAYLIS P. H. , PIPPARD C. , GILL G. V. , BURD J. 
Published: March 2008

SUMMARYA cytochemical assay has been developed to measure human plasma arginine vasopressin. It is based on the stimulation of Na+‐K+, ATPase activity located in the outer medulla of the rat kidney, and is capable of detecting very low plasma arginine vasopressin concentrations, limit of detection 0·01 pmol/l. Specificity for vasopressin stimulation of the enzyme is conferred on the assay by the use of specific vasopressin antiserum. Index of precision of the assay is 0·21. Degradation of arginine vasopressin in plasma in inhibited by phenanthro‐line. Samples may be stored up to 8 weeks at ‐ 70°C. Intra‐ and inter‐assay coefficients of variation were 22% (n= 8) and 104% (n=12), respectively. A sustained water load in eight healthy male adults caused a fall in plasma osmolality from a basal of 286·5±2·0 (mean±SEM) to 279·2 ± 2·4 mmol/kg after the load (P> 0.001), which was associated with a reduction in urine osmolality from 867 ± 54 to 69 ± 3 mmol/kg. Plasma immunoreactive arginine vasopressin fell from 1·3 ± 0·3 pmol/l to become undetectable (<0.3 pmol/l), but plasma cytochemical arginine vasopressin decreased from 0·96 ± 0·14 to 0.07 ± 0.02 pmol/l. There was a curvilinear relationship between plasma osmolality and plasma cytochemical arginine vasopressin, which militated against the concept of an osmotic threshold for vasopressin release.
HUMAN PANCREATIC GROWTH HORMONE RELEASING HORMONE FAILS TO STIMULATE HUMAN GROWTH HORMONE BOTH IN CUSHING'S DISEASE AND IN CUSHING'S SYNDROME DUE TO ADRENOCORTICAL ADENOMA
Authors: SMALS A. E. M. , PIETERS G. F. F. M. , SMALS A. G. H. , BENRAAD TH. J. , KLOPPENBORG P. W. C. 
Published: March 2008

SUMMARYAn absent or severely blunted hGH response to an i.v. bolus injection (100 μg) of human pancreatic growth hormone releasing hormone (hpGRF1–44) was found in seven female patients with Cushing's syndrome (five with pituitary dependent Cushing's disease and two due to an adrenal adenoma) and four men with pituitary dependent Cushing's disease. Three of the female and three of the male patients had an adequate hypoglycaemia after insulin administration. All these patients showed an absent or blunted hGH response after insulin induced hypoglycaemia. The GHRH data in these patients are in agreement with those in older literature on hGH responsiveness to stimuli such as L‐dopa, arginine and insulin induced hypoglycaemia. It is concluded that hypercortisolism inhibits hGH release to various stimuli at the pituitary level.
HUMAN PLATELET ARGININE VASOPRESSIN
Authors: NUSSEY S. S. , ANG V. T. Y. , BEVAN D. H. , JENKINS J. S. 
Published: March 2008

SUMMARYApproximately 90% of arginine vasopressin circulating in blood is associated with the platelets. Studies in six patients with cranial diabetes insipidus indicate that the platelet vasopressin originates in the hypothalamus and is taken up from plasma. Extracted platelet vasopressin is chromatographically identical to the posterior pituitary peptide and biologically active. Infusion of low‐doses of exogenous vasopressin into 10 normal male subjects caused a marked rise in both plasma and platelet hormone concentrations. Stimulation of endogenous vasopressin release by hypertonic saline (0·51 mol/l) infusion for 135 min in five male subjects also caused a rise in platelet and plasma peptide concentrations. In seven male smokers, the deep inhalation of two consecutively smoked unfiltered cigarettes caused a significant rise in both platelet and plasma vasopressin. Baseline platelet vasopressin concentrations in the smokers were higher than in the non‐smoking males even after 10 hours abstinence.
COMPARATIVE EVALUATION OF CYCLIC AMP AND IODIDE ACCUMULATION RESPONSES TO THYROID‐STIMULATING IMMUNOGLOBULINS IN CULTURED FRTL‐5 CELLS
Authors: BIDEY S. P. , EKINS R. P. 
Published: March 2008

SUMMARYThe rat thyroid cell strain FRTL‐5 was used to investigate the relationship between cyclic AMP and iodide accumulation responses to thyroid‐stimulating immunoglobulins (TSIg). Immunoglobulin G‐enriched precipitates of sera from 19 of 21 (90%) newly‐diagnosed Graves' disease patients gave significant (P > 0.01) accumulation of iodide (125I), and 16 of these also stimulated intracellular cyclic AMP. Correlation was poor however, with certain TSIg preparations giving widely divergent responses. After initiation of antithyroid treatment, 40% of sera investigated contained TSIg detectable in both bioassay systems, and all but one of the remainder were stimulatory in one of the two bioassays. All patients in remission were devoid of detectable TSIg as determined by iodide accumulation, although a single preparation stimulated cyclic AMP accumulation. LATS‐B, a lyophilized reference serum preparation containing high TSIg activity, enhanced iodide accumulation, which showed evidence of correlation with intracellular cyclic AMP at doses above 0.5 mU/ml. At lower doses, iodide accumulation was observed in the absence of detectable cyclic AMP accumulation. TSH and LATS‐B‐induced iodide accumulation were enhanced, and iodide efflux reduced, by the anion channel blocker 4–4 diisothiocyanate stilbene 2,2′ disulphonic acid (DIDS). In contrast, Ig‐enriched fractions of normal sera decreased both basal and stimulated iodide accumulation, but were without effect on efflux. TSIg from untreated Graves' sera gave widely‐differing iodide accumulation responses which showed poor correlation with both intracellular cyclic AMP and cyclic‐AMP‐ independent iodide efflux. This clear dissociation of responses to serum Ig preparations suggests that iodide uptake in FRTL‐5 cells, which do not organify iodide, may be subject to variable effects of non‐TSIg components of Graves' sera, on both iodide uptake itself, and as inhibitors of TSIg‐induced accumulation of intracellular cyclic AMP.
SERUM IMMUNOREACTIVE SOMATOMEDIN‐C LEVELS IN GROWTH FAILURE AND DELAYED PUBERTY ASSOCIATED WITH CHRONIC HEPATOSPLENIC SCHISTOSOMIASIS
Authors: CAVALIERE H. , LEITE Z. , MEDEIROS‐NETO G. 
Published: March 2008

SUMMARYEleven patients, five males, six females, aged 14–20 years with hepatosplenic schistosomiasis (HSS), growth failure and delayed puberty were submitted to endocrine evaluation. All patients had well preserved parenchymal liver function although several changes were present in the portal system, showing a poorly vascularized liver. Bone age was retarded, thyroid function was normal, the human growth hormone response to hypoglycaemia was within the normal limits and the prolactin response to TRH was normal. LH and FSH basal levels were normal and a normal rise was observed after a provocative test with LHRH. Gonadal function, expressed as serum testosterone or oestradiol levels, was abnormally low for the chronological age. Serum somatomedin‐C levels were also low (range 0·11–2·10 U/ml) for the respective Tanner stage or bone age of each individual patient. One year after a splenorenal shunting in the three patients that returned for follow‐up, it was observed that sexual maturation reached Tanner stage III, linear growth increment ranged from 9·0 to 11·5 cm and serum somatomedin‐C levels increased to 4·3–5·6 U/ml. We concluded that a combination of undernutrition and marked vascular changes in the liver, present in HSS, are associated with decreased serum sex steroids and somatomedin‐C concentrations, resulting in growth failure and delayed puberty in these patients.
EFFECTS OF HIGH DOSE KETOCONAZOLE THERAPY ON THE MAIN PLASMA TESTICULAR AND ADRENAL STEROIDS IN PREVIOUSLY UNTREATED PROSTATIC CANCER PATIENTS
Authors: DE COSTER R. , CAERS I. , COENE M.‐C. , AMERY W. , BEERENS D. , HAELTERMAN C. 
Published: March 2008

SUMMARY In vitro, ketoconazole has been shown to block testicular and adrenal 17,20‐lyase, which converts progestins to androgens. At higher concentrations, it also inhibits 11β‐hydroxylase, 20,22‐desmolase and 17α‐hydroxylase. To determine the differential hormonal effects of a 2‐week ketoconazole high‐dose therapy, the plasma levels of 10 major androgens, gluco‐ and mineralocorticoids were measured in 14 previously untreated patients with metastatic prostate cancer. Within 24 h, plasma testosterone fell from 14·6 ± 1·4 nmol/l (mean ± SEM) to 3·7 ± 0·7 nmol/l. Thereafter, it decreased to about 2·5 nmol/l and remained at that level. Plasma androstenedione and dehydroepiandrosterone decreased more gradually, respectively from 3·1 ± 0·4 nmol/l to 0·64 ± 0·17 nmol/l and from 6·6 ± 1·0 nmol/l to 2·82 ± 0·55 nmol/l (on day 14). In contrast, 17α‐hydroxyprogesterone and progesterone rose respectively 2‐ and 5‐fold. Plasma cortisol and aldosterone levels remained unchanged whereas 11‐deoxycorticosterone and 11‐deoxycortisol rose by factors of 14 and 6·7 respectively. Plasma corticosterone also increased, but to a much lesser extent (3‐fold). These results demonstrate that ketoconazole high dose therapy blocks mainly the 17,20‐lyase of both adrenal and testis. In addition it inhibits mitochondrial 11β‐hydroxylase to a lesser extent. The inhibition of 20,22‐desmolase also seems to be of little clinical relevance. However, since clinical or laboratory symptoms suggestive of hypo‐adrenalism have been reported in a small minority of patients, replacement therapy should be considered in such cases.
EFFECTS OF SOMATOSTATIN ANALOGUE SMS 201–995 IN NORMAL MAN
Authors: DAVIES R. R. , MILLER MARGARET , TURNER S. J. , GOODSHIP T. H. J. , COOK D. B. , WATSON M. , McGILL A. , ØRSKOV H. , ALBERTI K. G. M. M. , JOHNSTON D. G. 
Published: March 2008

SUMMARYLong‐acting somatostatin analogues may be of benefit in certain hypersecretory endocrine and gastrointestinal disorders. The 24 h hormonal and metabolic profiles of six normal male subjects receiving a twice daily subcutaneous injection of one such analogue SMS 201–995, 50 μg, has been compared to that obtained following placebo injection. Spontaneous daytime peaks of GH secretion were delayed until 1400 h following SMS 201–995 but nocturnal and total 24 h GH secretion were unaffected. The nocturnal rise in thyrotrophin was abolished by SMS 201–995 but thyroid function was unaffected. Insulin levels were suppressed following SMS 201–995 and the response to meals was inhibited. Glucose intolerance followed main meals. Glucagon levels were suppressed for up to 6 h. Circulating alanine levels were raised between 1200 h and 0600 h and there were intermittent elevations in lactate, pyruvate, glycerol and 3‐hydroxybutyrate. Amino acid levels, including branched chain amino acids, were also increased. All six subjects suffered gastrointestinal side‐effects. SMS 201–995, 50 μg, given twice daily shortly before meals does not suppress 24 h GH secretion, but demonstrates significant effects on metabolism and causes side effects in normal subjects.
THE LONG‐TERM EFFECTS OF MEGAVOLTAGE RADIOTHERAPY AS SOLE OR COMBINED THERAPY FOR LARGE PROLACTINOMAS: STUDIES WITH HIGH DEFINITION COMPUTERIZED TOMOGRAPHY
Authors: JOHNSTON D. G. , HALL K. , KENDALL‐TAYLOR P. , ROSS W. M. , CROMBIE A. L. , COOK D. B. , WATSON M. J. 
Published: March 2008

SUMMARYThe long‐term sequelae of external pituitary irradiation alone or in combination with surgery and/or bromocriptine therapy have been studied in 14 patients with large prolactinomas over an observation period of 6–22 years (mean 13 years). Galactorrhoea was abolished in four of the five females with this symptom, but menstrual disturbance persisted in five of six patients. Sexual function was normal without sex hormone replacement in only one of the eight males after treatment. Neurological deficits were abolished or improved by treatment in all 9 patients with this presentation. Serum prolactin levels declined after treatment (P > 0·001) and fell to within the normal range off bromocriptine therapy in six of the 14 patients at a mean of 9 years (range 5–17 years) after radiotherapy. All patients had anterior pituitary deficiency of some degree at reassessment, and 13 required replacement treatment. Serial skull radiographs revealed remineralization of the fossa floor in five patients and a decrease in fossa size in three. All five patients who did not also have surgery had evidence of tumour shrinkage without bromocriptine treatment (on CT scan or metrizamide cisternography). Fourth generation CT scans on completion of the study revealed a decrease in tumour mass in all patients, with varying degrees of empty sella in 13 and a cystic intrasellar tumour in the remaining one. Residual tumour was demonstrated in 10 patients, three of whom had normal serum prolactin levels, while one patient without visible tumour had persistent hyperprolactinaemia. Radiotherapy, alone or in combination with surgery and bromocriptine, effectively decreases prolactin secretion and tumour size in patients with large prolactinomas at the expense of other anterior pituitary function. Circulating prolactin levels are a poor marker of residual tumour volume.
A STUDY OF CORTICOTROPH ADENOMAS IN CUSHING'S DISEASE: NO EVIDENCE OF INTERMEDIATE LOBE ORIGIN
Authors: McNICOL ANNE M. , TEASDALE G. M. , BEASTALL G. H. 
Published: March 2008

SUMMARYThere is little evidence for a separate functional or anatomical intermediate lobe in the adult human pituitary gland. Nevertheless, Lamberts et al. (1982) proposed that a subgroup of corticotroph adenomas in Cushing's disease arise in that lobe and can be identified by the presence of argyrophil (? neural) fibres, and that these tumours are more often associated with corticotroph hyperplasia and hyperprolactinaemia than those arising in the anterior lobe. We have examined a series of corticotroph adenomas from patients with Cushing's disease for evidence of argyrophil fibres, and have correlated this with tumour site, corticotroph distribution in the para‐adenomatous gland, serum PRL levels and PRL immunoreactive cells in the tumour. Argyrophil fibres were identified not only in tumours adjacent to the posterior lobe, but also in tumours situated deep in the anterior lobe. There was no correlation between the presence of fibres or the site of the tumour and corticotroph hyperplasia. Whilst the two patients with the highest serum PRL levels did have argyrophil fibres they also had a subpopulation of PRL immunoreactive cells in the tumour. On the basis of these results, we propose that the ‘intermediate lobe’ hypothesis as outlined above should not be accepted.
STUDIES OF HYPOTHALAMIC PITUITARY STRUCTURE AND FUNCTION IN PATIENTS PREVIOUSLY TREATED WITH BILATERAL ADRENALECTOMY ALONE FOR CUSHING'S DISEASE
Authors: BEACOM R. , ATKINSON A. B. , KENNEDY A. L. , SHERIDAN B. , HADDEN D. R. , MERRETT J. D. , McILRATH E. 
Published: March 2008

SUMMARYA controversy still exists in regard to hypothalamic pituitary function long‐term after cure of hypercortisolism due to Cushing's disease. In an attempt to resolve this controversy, we have studied 15 patients, treated at least 6 years previously, by bilateral adrenalectomy. None of these patients had had pituitary‐directed therapy. The maximum increment response of serum TSH in response to TRH was < 5 mU/l in 13 of the 15. Serum PRL response to TRH, GH response to insulin‐induced hypoglycaemia, gonadotrophin responses to LHRH and nocturnal PRL secretion were normal in all patients studied. When nocturnal GH secretion was corrected for age, body mass index and menopausal status it was definitely abnormal in only two patients. The mean nocturnal GH secretion did not differ from that measured in a control group of Addisonian patients. The series of patients also did not differ significantly from the Addisonian patients in relation to the pattern of changes in plasma ACTH, over 24 h after an 0800 h oral dose of hydrocortisone. There was a significant rise in plasma ACTH between 2200 h and 0600 h in both groups of patients. The plasma ACTH concentrations were significantly higher in post‐adrenalectomy patients. Hypothalamic pituitary function is normal in the long‐term in the majority of patients treated by bilateral adrenalectomy for Cushing's disease.
PITUITARY PRO‐OPIOMELANOCORTIN‐CELL CARCINOMA OCCURRING IN CONJUNCTION WITH A GLIOBLASTOMA IN A PATIENT WITH CUSHING'S DISEASE AND SUBSEQUENT NELSON'S SYNDROME
Authors: GABRILOVE J. L. , ANDERSON P. J. , HALMI N. S. 
Published: March 2008

SUMMARYPituitary carcinoma is defined as a malignant pituitary tumour associated with blood‐ or lymph‐borne metastases. Cushing's disease is frequently present in patients with this condition. After adrenalectomy for Cushing's disease, a 37‐year‐old man developed Nelson's syndrome resulting from a pituitary carcinoma with metastases to the spinal cord, cauda equina, heart, liver, and pancreas. The primary tumour and its metastases showed immunocytochemical staining for ACTH, β‐lipotrophin, and variably for β‐endorphin and α‐melanocyte stimulating hormone (α‐MSH). A coincidental glioblastoma was also present. Nine cases of Cushing's disease associated with pituitary carcinoma, including the present patient, are documented in the literature. The case reported is only the second in which immunohistochemical staining of the primary pituitary tumour and its metastases was performed, and the first in which ACTH‐related peptides, in addition to ACTH itself, were demonstrated in the carcinoma cells.
EFFECT OF THE ANTI‐THYROID DRUG METHIMAZOLE ON INTERLEUKIN‐1 AND INTERLEUKIN‐2 LEVELS IN VITRO
Authors: WEETMAN A. P. 
Published: March 2008

SUMMARYThere is now good evidence that anti‐thyroid drugs such as methimazole have immunomodulatory effects which may be important in the treatment of patients with Graves' disease, but the immunological mechanisms by which these agents act are not clear. This study has examined the effect of methimazole on four important soluble mediators of the immune response, interleukin‐1 (IL‐1), interleukin‐2 (IL‐2), γ‐interferon (γ‐IFN) and B‐cell differentiation factor (BCDF). When peripheral blood mononuclear cells from normal subjects were stimulated with mitogens (phytohaemagglutinin, concanavalin A or pokeweed mitogen) in the presence of 10–100 μmol/l methimazole, there was an increase in IL‐2 activity in the culture supernatants. This effect was apparent between 24 and 60 h: enhanced proliferation of T‐cells was also seen in methimazole‐supplemented cultures. There was no effect of the drug on IL‐2 receptor expression or on IL‐1 and γ‐IFN production. BCDF was increased by methimazole in one of three experiments with pokeweed mitogen but not in three experiments with concanavalin A. These results suggest that the enhancement of mitogen‐stimulated T‐cell proliferation in vitro with methimazole is due to an increase in the IL‐2 available to the T‐cells in these cultures. Thus the in‐vivo immunological effects of these drugs are likely to be complex since they may have at least two, possibly related, actions on the intrathyroidal lymphoid infiltrate, namely inhibiting oxygen radical generation and increasing IL‐2 levels.
POSTOPERATIVE PLASMA GH LEVELS AND RESTORATION OF GH DYNAMICS IN ACROMEGALIC PATIENTS SURGICALLY TREATED BY THE TRANSSPHENOIDAL APPROACH
Authors: KARASHIMA T. , KATO K. , NAWATA H. , IKUYAMA S. , IBAYASHI H. , NAKAGAKI H. , KITAMURA K. 
Published: March 2008

SUMMARYIn 44 patients with acromegaly treated by transsphenoidal pituitary microsurgery, the relationship between changes in pre‐ and post‐operative GH dynamics and postoperative fasting plasma GH levels was examined to clarify which is the optimal approach for evaluating postoperative removal of the tumour. TRH, LHRH and bromocriptine tests, which act directly on the pituitary somatotroph, and the oral glucose tolerance test (oGTT) and insulin tolerance test (ITT), which act via hypothalamus, were carried out pre‐ and post‐operatively. Abnormal responses postoperatively were found in most patients with fasting postoperative plasma GH over 5 ng/ml. In 24 patients with postoperative fasting plasma GH level of 5 ng/ml or below, 7 of 17 (41%) showed abnormal responses in the TRH test, 2 of 5 (40%) in the LHRH test and 3 of 13 (23%) patients in the bromocriptine test. All patients with a fasting plasma GH level less than 10 ng/ml, except for those with panhypopituitarism, showed normal responses to ITT and the paradoxical increases with the oGTT were absent. These results indicate that abnormal responses caused by a direct action on adenoma cells do not necessarily disappear even when the fasting plasma GH level is below 5 ng/ml. Abnormal responses caused by indirect actions, through the hypothalamus, disappear when the level is less than 10 ng/ml.