bluuebunny/crossref_metadata_2025_split huggingface dataset:
THE INFLUENCE OF ANTITHYROID DRUGS AND IODINE ON THYROID CELL MHC CLASS II ANTIGEN EXPRESSION
Authors: DAVIES TERRY F. , YANG CLEMENT , PLATZER MICHAEL 
Published: March 2008

SUMMARYWe have investigated the influence of antithyroid drugs (methimazole and propylthiouracil) and sodium iodide on the expression of major histocompatibility (MHC) class II antigen expression in human and rat thyroid cells. While methimazole and propylthiouracil significantly inhibited lectin‐induced MHC class II (HLA‐DR) antigen in crude human thyroid monolayer preparations these drugs had no influence on γ‐interferon induction of class II antigens in similar cell preparations. Hence, antithyroid drugs probably had a direct effect on thyroid monolayer T cells which are known to effect the lectin induction of MHC class II antigen via T‐cell secretion of the cytokine, γ‐interferon (IF). Sodium iodide, similarly, had no direct influence on human thyroid cell MHC class II antigen expression induced by γ‐IF. However, iodide significantly inhibited the γ‐IF‐induced expression of MHC class II antigens in a proliferating rat thyroid cell clone derived from FRTL‐5 cells (clone 1B‐6). In the rat thyroid cell clone this antagonistic action appeared to be exerted via inhibition of TSH‐induced proliferation.These data add further support to the multifactorial nature of the profound immunosuppressive influence of antithyroid drugs in autoimmune thyroid disease and experimental thyroiditis. In contrast, iodides may have a major, and often overlooked, influence on thyroid cell proliferation and antigen expression.
ANTITHYROID DRUGS IN THE TREATMENT OF HYPERTHYROIDISM OF Graves' DISEASE: LONG‐TERM FOLLOW‐UP OF 434 PATIENTS
Authors: HEDLEY A. J. , YOUNG R. E. , JONES S. J. , ALEXANDER W. D. , BEWSHER P. D. ,   SCOTTISH AUTOMATED FOLLOW‐UP REGISTER GROUP
Published: March 2008

SUMMARYA study of antithyroid drug (ATD) therapy with a mean follow‐up period of 10 years (range 2–25) in 434 patients with Graves' disease has been made by linking hospital records with those of a central follow‐up register. The majority (89%) were treated with carbimazole and 87% received combined therapy with triiodothyronine (T3) (73%) or thyroxine (T4) (14%). Sixty‐one per cent were assessed for T3 suppression tests on completion of treatment, of whom 61% (95% CL, 55‐67%) suppressed. The overall 5‐year cumulative proportion developing recurrent hyperthyroidism was 54‐62% with rates of 26‐44% in suppressed patients and 65‐79% in those not suppressed. In unsuppressed patients, most (72%) of the recurrences occurred within 1 year with only an additional 10% predicted up to 10 years. In suppressed patients 30% of recurrences occurred in the first year, 60% between 1 and 5 years and a further 10% between 5 and 10 years. Suppression with T3 is probably the best and cheapest predictor of outcome but has an accuracy of only 70% for both positive and negative tests which limits its usefulness in planning long‐term follow‐up and surveillance. A standard format should be adopted for the analysis and reporting of follow‐up studies, based on actuarial methods of estimating the cumulative proportion with recurrences or other events, to facilitate comparisons between different centres.
RELATIONSHIP BETWEEN THE PUBERTAL FALL INSEX HORMONE BINDING GLOBULIN AND INSULIN‐LIKE GROWTH FACTOR BINDING PROTEIN‐I. A SYNCHRONIZED APPROACH TO PUBERTAL DEVELOPMENT?
Authors: HOLLY J. M. P. , SMITH C. P. , DUNGER D. B. , HOWELL R. J. S. , CHARD T. , PERRY L. A. , SAVAGE M. O. , CIANFARANI S. , REES L. H. , WASS J. A. H. 
Published: March 2008

SUMMARYIn a cross‐sectional study of 69 normal adolescents we have found sex hormone‐binding globulin (SHBG) levels to fall in both males and females throughout the pubertal period. Multiple regression analysis revealed a close negative correlation with insulin in both sexes. Weaker correlations were also found between SHBG and circulating androgen concentrations, in both males and females. Similar results were also obtained for a second circulating binding protein of primarily hepatic origin. This low molecular weight insulin‐like growth factor (IGF) binding protein I (IBP‐I) is one of two distinct classes of IGF binding proteins which bind IGF‐I and IGF‐II. IGF‐I in turn mediates, at least in part, the actions of growth hormone. IBP‐I also fell throughout puberty, correlating with the increasing insulin levels. In addition IBP‐I correlated with androgen levels in both sexes. These similarities between SHBG and IBP‐I, together with a strong correlation across puberty between the levels of the two binding proteins themselves (r= 0.737, P < 0.001), suggest common mechanisms of control over the circulating levels of these two binding proteins. The association with insulin raises the possibility of a synchronized modulation of the actions of sex steroids and IGFs by nutritional intake. Thus pubertal growth and sexual development may occur over the same time with both modulated according to nutritional intake, linked through pancreatic insulin release, to hepatic production of SHBG and IBP‐I.
PERIFUSION OF HUMAN GRANULOSA‐LUTEAL CELLS: RESPONSE TO LH STIMULATION
Authors: WEISS T. J. , STEELE P. A. , UMAPATHYSIVAM K. 
Published: March 2008

SUMMARYLH pulse frequency and amplitude vary significantly during the menstrual cycle; however, it is not clear what significance the secretory pattern has for the ovary. We have developed an in‐vitro perifusion system in which luteinized human granulosa cells (GC) can be exposed to various patterns of gonadotrophin stimulation. GC were recovered following follicle aspiration for in‐vitro fertilization, grown on Cytodex‐3 for 6 days, and then perifused with medium containing LH (or hCG), delivered with differing pulse frequencies and amplitudes. When pulses of LH were applied to the cells, progesterone secretion rose initially and then fell to the baseline as the LH concentration declined. Pulsatile administration of LH, over a period of 10 h, stimulated progesterone secretion more efficiently than did continuous LH. Finally, delivery to the cells of pulses of hCG, a ligand known to bind to the LH receptor but with binding characteristics distinct from those of LH, failed to elicit pulses of progesterone.
RETURN OF FERTILITY AFTER TWELVE YEARS OF AUTOIMMUNE OVARIAN FAILURE
Authors: TAYLOR R. , SMITH N. M. , ANGUS B. , HORNE C. H. W. , DUNLOP W. 
Published: March 2008

SUMMARYAutoimmune ovarian failure is widely regarded as irreversible, although ovarian biopsy characteristically shows follicles surrounded by lymphocytes. Two previous reports of pregnancy in this condition both followed institution of steroid replacement therapy (Finer et al., 1985; Cowchock et al., 1988). We report a case in which fertility spontaneously returned to normal twelve years after the diagnosis of autoimmune ovarian failure.
THE KIDNEY IS THE MAJOR SITE OF CORTISONE PRODUCTION IN MAN
Authors: WHITWORTH J. A. , STEWART P. M. , BURT D. , ATHERDEN S. M. , EDWARDS C. R. W. 
Published: March 2008

SUMMARYThe major site of cortisol metabolism in man has been thought to be the liver. Studies in patients with either congenital or acquired deficiency of 11β‐hydroxysteroid dehydrogenase (an enzyme responsible for the interconversion of cortisol to cortisone) suggested that the kidney was an important site of cortisone production.In 88 patients with proven renal disease but normal liver function, arbitrarily divided into four groups on the basis of plasma creatinine, 0900 h plasma cortisone was significantly reduced in all groups when compared with 47 controls (e.g. 21 ± 3 nmol/1 (mean ± SEM) in patients with plasma creatinine >0.45 mmol/1 vs 62 ± 3 nmol/1 in controls, P < 0.001). 0900 h plasma cortisol was not significantly different. There was an inverse correlation between plasma creatinine and plasma cortisone (r=−0.55, p < 0.01). Four anephric patients had a 0900 h plasma cortisone level of 6 ± 1 nmol/1.We conclude that the kidney is a major site for the conversion of cortisol to cortisone and hence cortisone production in man. The relevance of this to the pathophysiology of salt and water metabolism in renal disease remains to be elucidated.
EFFECT OF CV 205‐502 IN HYPERPROLACTINAEMIC PATIENTS INTOLERANT OF BROMOCRIPTINE
Authors: NEWMAN CONNIE B. , HURLEY ARLENE M. , KLEINBERG DAVID L. 
Published: March 2008

SUMMARYCV 205‐502 (Sandoz), an octahydrobenzol [g]quinoline, is a long‐acting dopamine agonist which inhibits prolactin secretion. We conducted a phase 2 clinical study in 10 hyperprolactinaemic women (nine of whom were previously intolerant of bromocriptine) in order to determine (1) the dose at which CV 205–502 exerted its prolactin‐lowering effect; (2) the nature of adverse reactions associated with long‐term therapy; and (3) whether patients who were intolerant of bromocriptine could tolerate CV 205–502. At first patients were randomized to take initial doses of either 0.02 or 0.05 mg daily at bedtime. Thereafter these doses of medication were gradually increased either to the point of normalizing serum prolactin (to 0.70 IU/1 or 20 ng/ml) or to a maximum dose of 0.14 mg daily. The lower initial dose was ineffective and had to be increased in all patients. The higher initial dose (0.05 mg) normalized prolactin in three of five women within 24 h. During chronic administration of the final dose of CV 205–502 (mean 0.09 mg a day), serum prolactin decreased from a mean level of 9.19 |Mp 4.9 (SEM) IU/1 to a mean level of 1.55 ± 0.49 IU/1 (n= 10 patients). Prolactin was normalized in five patients. Two patients, one of whom had been previously unresponsive to bromocriptine, and another unresponsive to pergolide with regard to prolactin inhibition, were also unresponsive to CV 205–502. Nausea, the side‐effect responsible for these patients' previous intolerance of bromocriptine, occurred in six of 10 patients taking CV 205‐502 but was much less disabling and did not cause any of the patients to stop this medication. Only one patient taking CV 205‐502 discontinued treatment because of adverse effects (light‐headedness).
TESTICULAR ENLARGEMENT AND ELEVATED SERUM INHIBIN CONCENTRATIONS OCCUR IN PATIENTS WITH PITUITARY MACROADENOMAS SECRETING FOLLICLE STIMULATING HORMONE
Authors: HESELTINE D. , WHITE M. C. , KENDALL‐TAYLOR P. , DE KRETSER D. M. , KELLY W. 
Published: March 2008

SUMMARYWe studied four male patients with pituitary macroadenomas. Before treatment all had high serum FSH concentrations, but LH and testosterone were normal or subnormal; all patients were found to have large testes. All had had normal sexual function, and three patients had fathered children. After pituitary surgery there were decreases in serum gonadotrophins and testosterone, which were accompanied by decreases in testicular volumes. hCG stimulation tests in two patients showed normal responses of testosterone and oestradiol, confirming normal Leydig cell function. Inhibin levels were increased in two patients studied when FSH levels were high, suggesting a defect in gonadal‐pituitary feedback control. Later, as FSH concentrations decreased to normal, so did inhibin levels. Histology showed that increased testicular size was due to increased lengths of seminiferous tubules. The association of pituitary macroadenomas, large testes and increased serum inhibin has not been reported previously. Assessment of testicular size in patients with raised serum FSH is important, since enlarged testes suggest the likely pathogenesis is that of a pituitary gonadotrophinoma, rather than primary gonadal failure. Increased inhibin levels may then confirm this, and be a biochemical marker for these tumours.
VIRILIZING ADRENAL ADENOMA IN AN ADULT WITH THE BECKWITH‐WIEDEMANN SYNDROME: PARADOXICAL RESPONSE TO DEXAMETHASONE
Authors: CLOUSTON W. M. , CANNELL G. C. , FRYAR B. G. , SEARLE J. W. , MARTIN N. I. , MORTIMER R. H. 
Published: March 2008

SUMMARYAn adult woman with Beckwith‐Wiedemann syndrome, hemihypertrophy and an androgen‐secreting adrenal adenoma is described. She presented with a 7‐year history of progressive virilization and was found to have high plasma levels of testosterone and dehydroepiandrosterone (DHEA) sulphate and elevated levels of urinary metabolites of testosterone and its precursors. Administration of dexamethasone was associated with progressive rises in plasma 17 αOH progesterone, 11β‐desoxycortisol, DHEA sulphate, androstenedione and testosterone, together with increased urinary excretion of androsterone, 11βOH androsterone, etiocholanolone, DHEA, and 16αOH DHEA. Hormone levels fell to normal following removal of the tumour.
COMPARISON OF THE ACTH AND CORTISOL RESPONSES TO PROVOCATIVE TESTING WITH GLUCAGON AND INSULIN HYPOGLYCAEMIA IN NORMAL SUBJECTS
Authors: LITTLEY M. D. , GIBSON S. , WHITES A. , SHALET M. 
Published: March 2008

SUMMARYThe glucagon stimulation test (GST) is often used to assess pituitary ACTH reserve, particularly when other tests are contra‐indicated. In a preliminary investigation, in patients with pituitary disease, we failed to demonstrate the ACTH dependence of the cortisol response. We have therefore compared the ACTH, cortisol and glucose responses to glucagon (1 mg s. c.), insulin (0.2 U/kg i. v., ITT) and placebo in six healthy male volunteers, sampling every 10 min for 6 h. During the GST, mean |Mp SD serum cortisol rose from 256 ± 80 nmol/1 to a peak of 481 ± 164 nmol/1 (range 289–717 nmol/1, P < 0.01) in comparison with 280 ± 81 nmol/1 to 602 ± 110 nmol/1 (range 493‐742 nmol/1) during the ITT (P < 0.002). The mean peak cortisol levels achieved in the two tests did not differ significantly. In the GST, plasma ACTH rose from a mean basal value of 10.9 ± 16.6 ng/1 to a mean peak level of 123 ± 76 ng/1 (P < 0.02) (ACTH ng/ 1 × 0.225 = pmol/1). The corresponding values in the ITT were 7.1 ± 16.2 ng/l and 263 ± 91 ng/1(P < 0.001). The mean peak ACTH level was significantly greater during the ITT (P < 0.05). Thus the cortisol response was ACTH dependent in both the GST and the ITT in normal subjects. Furthermore, the ACTH response was of sufficient duration to be detected by the usual procedure of sampling every 30 min. However, in clinical practice, more prolonged sampling should be undertaken during the GST, as two subjects showed their peak cortisol response after 3 h. In addition, this study suggests that the ‘normal’response to GST requires redefinition in view of four subjects in whom the peak cortisol response was less than 500 nmol/1.
DIFFUSE SCLEROSING PAPILLARY CARCINOMA OF THYROID: A WOLF IN SHEEP'S CLOTHING
Authors: WU PATRICIA S‐C. , LESLIE PETER J. , McLAREN KATHRYN M. , TOFT ANTHONY D. 
Published: March 2008

SUMMARYWe describe three patients with a rare, and only recently reported, variant of papillary carcinoma of the thyroid. In each case the clinical presentation and biochemical or serological findings were indicative of benign disease.
INFLUENCE OF OESTRADIOL AND PROGESTERONE ON PULSATILE LH SECRETION IN POSTMENOPAUSAL WOMEN
Authors: CAGNACCI ANGELO , MELIS GIAN BENEDETTO , PAOLETTI ANNA MARIA , GAMBACCIANI MARCO , SOLDANI RENZA , SPINETTI ADRIANA , FIORETTI PIERO 
Published: March 2008

SUMMARYPulsatile LH secretion was studied in six healthy postmenopausal women. Blood samples were obtained every 10 min during an 8‐h saline infusion performed before and during the administration of transdermal oestradiol alone (E2; 50 μg/day) and in combination with vaginal progesterone (P; 100 mg twice daily). Plasma E2 and P levels reached values similar to those found in the early follicular phase and in the luteal phase of the menstrual cycle, respectively. The mean plasma LH levels significantly decreased (P < 0.01) during trans‐dermal E2 with and without vaginal P. A significant increase in the frequency (P < 0.025) and the amplitude (P <0.05) of LH pulses was observed during transdermal E2. The administration of vaginal P to oestrongenized women significantly blunted the frequency (P < 0.05) and enhanced the amplitude (P<0.05) of LH pulses. In all experimental conditions, the mean plasma LH levels showed a positive linear correlation with the amplitude of LH pulses. The present results show that peripheral levels of E2, similar to those of the early follicular phase of the menstrual cycle, can influence the pulsatile pattern of LH secretion, enhancing the frequency and the amplitude of LH pulses. In oestrogenized patients, the increase of peripheral P plasma levels to postovulatory values restored a pulsatile pattern of LH secretion similar to that of the early luteal phase of menstrual cycle.
CELL POPULATION KINETICS IN DOG AND HUMAN ADULT THYROID
Authors: COCLET J. , FOUREAU F. , KETELBANT P. , GALAND P. , DUMONT J. E. 
Published: March 2008

SUMMARYCell population kinetics was studied by bromodeoxyuridine (BrdU) histochemical and 3H thymidine radioautographic labelling in dog thyroids. In‐vivo labelling with BrdU and in‐vitro labelling of incubated slices with 3H thymidine gave similar results. This validates the use of in‐vitro labelling of slices for the study of cell kinetics in the thyroid. In‐vitro labelling of human thyroid slices demonstrated a labelling index of 13.4 ± 10−5 for follicular cells; assuming an S phase of 10 h, this corresponds to a turnover time of the order of 8.5 years for the follicular cells. Stromal cells appear to turn over faster. These results show for the first time that human thyroid cells divide about five times during adulthood and therefore that the steady state level of thyroid cell mass results from a balance between cell division and cell loss. A shorter turnover time was found as expected in the thyroid of an adolescent and in follicular colloid nodules.
HORMONES AND HYPERTENSION
Authors: FRASER ROBERT , DAVIES DAVID L. , CONNELL JOHN M. C. 
Published: March 2008

SummaryIt seems clear that hypertension may be a common feature of growth hormone excess, but precise frequency figures cannot be derived from current data due to bias and inadequate epidemiological study techniques. The mechanism of increased blood pressure is also unclear. There is clear evidence of gross sodium retention and hypertrophy of the heart and blood vessels but these occur in both normotensive and hypertensive acromegaly. This is also true of changes in body fluid volumes. Studies of changes in the levels of, and blood pressure sensitivity to, hormones such as ANF, angiotensin II and catecholamines are frequently contradictory and also difficult to interpret at present. The interrelationships between growth hormone, renal function and blood pressure require further careful study.
BROMOCRIPTINE THERAPY FOR NON‐FUNCTIONING PITUITARY ADENOMA
Authors: VAN SCHAARDENBURG D. , ROELFSEMA F. , VAN SETERS A. P. , VIELVOYE G. J. 
Published: March 2008

SUMMARYOver a 6‐year period, 25 patients with non‐functioning pituitary adenomas were treated with bromocriptine, while 18 other patients with this condition underwent surgery as the first therapeutic modality. The medically treated group, consisting of those patients without alarming eye symptoms, was analysed in retrospect. Eight of these patients had previously undergone surgery and radiotherapy. Bromocriptine was used in a dose of 5 to 22.5 mg per day; the mean duration of treatment was 18 months. For 11 patients, radiological findings obtained during the year before treatment with bromocriptine revealed progression in five cases and stable tumour size in the others. Three of the five patients with progression showed tumour size reduction during bromocriptine therapy while no further growth occurred in the other two. When medication was stopped in one responding patient, the tumour grew again. One other patient, without pretreatment radiological investigation, exhibited tumour size reduction during bromocriptine therapy, and one patient exhibited radiological progression during the study period. In one case visual fields improved and in one other deteriorated without parallel changes in tumour size on computerized tomography. The favourable reactions were equally divided between the groups with and without previous radiotherapy. We conclude that bromocriptine is rarely capable of reducing the size of non‐functioning pituitary adenomas (16% in this series). However, pituitary adenomas exhibiting recent growth may be sensitive to this drug, leading to size reduction or growth arrest.
INTERACTION OF CLONIDINE AND GHRH ON GH SECRETION IN VIVO AND IN VITRO
Authors: ALBA‐ROTH JULIA , LOSA MARCO , SPIESS YURIKO , SCHOPOHL JOCHEN , MÜLLER O. ALBRECHT , VON WERDER KLAUS 
Published: March 2008

SUMMARYTo investigate the mechanism by which clonidine stimulates GH‐secretion in vivo and in vitro, we studied its interaction with GHRH. In vivo: eight or six normal male subjects were submitted to five protocols: (1) 150 μg clonidine orally followed by 50 μg GHRH 1–44 i.v. 2 h later, (2) 50 μg GHRH 1–44 i.v. followed by 150 μg clonidine orally 2 h later, (3) 150 μg clonidine orally followed by GHRH i.v. 30 min later, (4) 300 μg clonidine orally followed by 50 μg GHRH i.v. 3 h later and (5) 50 μg GHRH i.v. followed by 300 μg clonidine orally 90 min later. In vitro: Rat anterior pituitary cells were coincubated with clonidine (10‐11, 10‐9, 10‐7 and 10‐5 m) and GHRH (0.005, 0.05, 10 nM) for 4h. Results: 150 μg clonidine alone does not stimulate GH‐secretion. Furthermore, the GH‐increase was not significantly different when GHRH bolus was given before, after or together with clonidine. When 300 μg clonidine was given before GHRH GH‐levels were significantly higher (max 28.6 ± 8.0 mU/1) at 90 min, compared to when clonidine was given after GHRH (max 7.8 ± 3.6 mU/1). The GHRH bolus after clonidine led to a significantly lower GH‐increase (max 31.6 μg 17.0 mU/1) compared to the GHRH‐induced GH‐increase (max 47.2 μg 13.0 mU/1) before clonidine. In vitro, clonidine had no stimulatory effect on GHRH‐stimulated GH secretion. These findings are compatible with clonidine leading to stimulation of GH by inducing endogenous GHRH release.
METHIMAZOLE‐INDUCED AGRANULOCYTOSIS IN JAPANESE PATIENTS WITH GRAVES’ DISEASE
Authors: TAMAI HAJIME , TAKAICHI YUKIHIKO , MORITA TETSUYA , KOMAKI GEN , MATSUBAYASHI SUNAO , KUMA KANJI , WALTER ROBERT M. , KUMAGAI LINDY F. , NAGATAKI SHIGENOBU 
Published: March 2008

SUMMARYWe reviewed the records of approximately 7000 Japanese patients whose hyperthyroidism was treated with methimazole (MMI) alone. Four patients (Group I) developed agranulocytosis during a second course of MMI therapy and eight patients (Group II) during an initial course. Six patients (three in each group) received less than 30 mg MMI daily. Agranulocytosis occurred after more than 2 months of therapy (12 weeks‐1 year) in five patients. Seven patients were less than 40 years of age. One patient displayed a gradual protracted development of agranulocytosis. These results indicate that agranulocytosis after MMI may occur irrespective of dose, age, duration of treatment, and with a second exposure.
ANTIGENICITY AND EFFICACY OF AUTHENTIC SEQUENCE RECOMBINANT HUMAN GROWTH HORMONE (SOMATROPIN): FIRST‐YEAR EXPERIENCE IN THE UNITED KINGDOM
Authors: BUZI F. , BUCHANAN C. R. , MORRELL D. J. , PREECE M. A. 
Published: March 2008

SUMMARYTwenty‐one children were treated for GH deficiency with authentic sequence biosynthetic human GH (somatropin), 60 μg/kg body weight, subcutaneously, three times weekly for 1 year or longer. The magnitude of growth response and rise in serum insulin‐like growth factor I levels were similar to those expected from experience with pituitary GH and somatrem. Three patients developed serum antibodies to GH with a binding capacity < 0.02 μg/l, but in only one patient was the GH binding capacity < 10 μg/l and he showed no attenuation of growth response. Eschericliia coli polypeptide antibodies did not rise significantly and no clinically important side‐effects occurred. Somatropin is safe, effective and of low immunogenicity in the treatment of GH deficiency.