bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effects of recombinant human insulin‐like growth factor I on growth hormone secretion in adolescents with insulin dependent diabetes mellitus
Authors: Cheetham Tim D. , Clayton Kharen L. , Taylor Alistair M. , Holly Jeff , Matthews David R. , Dunger David B. 
Published: March 2008

SummaryOBJECTIVE It has been proposed that low IGF‐I levels and reduced IGF‐I bioactivity may lead to elevated GH levels in adolescents with insulin dependent diabetes (IDDM). We have therefore studied the effects of human recombinant insulin‐like growth factor I (rhIGF‐I) administration on GH levels and GH secretion in adolescents with IDDM.PATIENTS Nine late pubertal adolescents (four male and five female) with IDDM.DESIGN A double‐blind placebo controlled study of rhIGF‐I administered subcutaneously in a dose of 40 μg/kg body weight at 1800 h.MEASUREMENTS IGF‐I and GH concentrations were measured at regular intervals throughout the study. Twenty‐two hour GH secretory rates were calculated by deconvolution analysis. Overnight GH profiles were analysed by distribution analysis, and Fourier transformations were performed on both overnight GH concentrations and GH secretory rates.RESULTS Mean IGF‐I levels over the 22‐hour study period were significantly elevated following rhIGF‐I administration (350 ± 26 vs 205 ± 21 μg/l (mean ± SEM), P<0 001). Mean 22‐hour GH levels were reduced following rhIGF‐I administration (19.4 ± 4.0 compared with 33.6 ± 5.8 mU/l; P= 001). Distribution analysis demonstrated that the reduction in GH levels was due to changes in the proportion of values at both high and low concentrations. Deconvolution analysis also revealed a significant overall reduction in GH secretory rate following IGF‐I administration (1.81 ± 0.30 vs 2.98 ± 0.47 mU/min, P= 0.01) which was still apparent during the final 5.5 hours of the study period (1.51 ± 0.30 vs 2.76 ± 0.61 mU/min, P= 002). The dominant periodicity of GH secretory episodes as determined by Fourier transformation was between 120 and 180 minutes after both IGF‐I and placebo.CONCLUSIONS In late pubertal adolescents with IDDM the rise in IGF‐I levels following rhIGF‐l administration in a subcutaneous dose of 40 μg/kg body weight leads to a significant reduction in GH levels and GH secretory rate. The reduction in GH secretion is due to changes in pulse amplitude rather than frequency. A reduction in GH secretion was apparent at the beginning and also towards the end of the 22‐hour study period.
Alteration of the circadian rhythm of intact parathyroid hormone following a 96‐hour fast
Authors: Fraser W. D. , Logue F. C. , Christie J. P. , Cameron D. A. , O'Reilly D. St J. , Beastall G. H. 
Published: March 2008

SummaryOBJECTIVE PTH(1‐84) secretion in normal male subjects follows a circadian rhythm. The control of this rhythm is multifactorial with both neuroendocrine and chemical influences. The aim of this study was to assess the effect of a 96‐hour fast on the circadian rhythm of PTH(1 ‐84), serum calcium, phosphate and nephrogenous cAMP (NcAMP), an index of PTH(1‐84) bioactivity.DESIGN Blood samples for estimation of all analytes were obtained over a 24‐hour period at 30‐minute intervals. Urine samples were obtained 4 hourly during the daytime and overnight. Each subject was studied on two occasions after being randomized to either (a) normal hospital diet or (b) a 96‐hour fast with water freely available.SUBJECTS Six healthy adult males aged between 28 and 40 years, mean 32 years.MEASUREMENTS PTH(1‐84) was measured by an in‐house immunoradiometric assay. Serum calcium, phosphate, albumin, creatinine and urinary creatinine were measured by standard automated techniques. Calcium was adjusted for albumin. Plasma cAMP was estimated by a commercial method and urine cAMP by in‐house radioimmunoassay and NcAMP obtained by calculation. Rhythm parameters were analysed by cosinor techniques. RESULTS There were alterations in the circadian rhythms of serum phosphate, PTH(1–84) and NcAMP following a 96‐hour fast. Fasting abolished the nocturnal rise in phosphate, PTH(1‐84) and NcAMP but had little effect on the pattern of adjusted calcium over a 24‐hour period. The mean concentrations of serum phosphate, adjusted calcium and NcAMP decreased significantly following the fast and mean PTH(1‐84) increased during day time.CONCLUSIONS Fasting for 96 hours significantly alters the circadian rhythm of PTH(1‐84) secretion by lowering the mean calcium concentration and attenuating the circadian rhythm of serum phosphate.
Detection of dimeric inhibin throughout the human menstrual cycle by two‐site enzyme immunoassay
Authors: Groome N. P. , Illingworth P. J. , O'Brien M. , Cooke I , Ganesan T. S. , Baird D. T. , McNeilly A. S. 
Published: March 2008

SummaryOBJECTIVE We have developed and validated a two‐site immunoassay for the measurement of dimeric inhibin in plasma and subsequently measured dimeric inhibin levels in plasma through the normal female menstrual cycle.DESIGN Recombinant inhibin added to plasma samples was quantitatively recovered in both follicular and luteal phase, and serial dilutions of samples were tested for parallelism to similar dilutions of recombinant 32kDa inhibin. Daily samples were assayed from four women through a menstrual cycle.PATIENTS (a) Four groups of six women who (i) were in the follicular phase of a normal menstrual cycle, (ii) were in the luteal phase of a normal menstrual cycle, (iii) were post‐menopausal and (iV) who had received hMG to induce superovulation. (b) Four healthy female volunteers aged 25–33.RESULTS Post‐menopausal women had less than 2ng/l of inhibin whereas six women treated with hMG had dimeric inhibin concentrations up to 1125ng/l.During the early follicular phase, at the time of onset of menstruation, extremely low levels of dimeric inhibin were found (3‐4ng/l (CI 2.2‐5.0)) while in the late follicular phase, there was a marked increase in dimeric inhibin concentration. The concentration of dimeric inhibin was maximal (65.6 ng/l (CI 53.1‐81,1)) in the mid‐luteal phase. The overall pattern of dimeric inhibin concentration during the menstrual cycle was similar to that observed with previous inhibin assays although the magnitude of change was considerably greater.CONCLUSION The human ovary, In particular the corpus luteum, secretes significant amounts of dimeric and therefore biologically active inhibin.
Short‐term fasting in normal women: absence of effects on gonadotrophin secretion and the menstrual cycle
Authors: Soules M. R. , Merriggiola M. C. , Steiner R‐ A. , Clifton D. K. , Toivola B. , Bremner W. J. 
Published: March 2008

SummaryOBJECTIVE In men and male monkeys, a short‐term fast has been reported to have a major effect on the reproductive axis. In this study we investigated the effects of a short‐term fast (72 hours) on female reproductive hormone secretion and menstrual function.DESIGN The study consisted of an admission day (control), three successive fasting days (fast 1, 2 and 3) and a refeeding day (post fast).PATIENTS Eight normal cycling women, ages 21–35, within 10% of ideal body weight, were fasted for 72 hours during the follicular phase of their menstrual cycle.MEASUREMENTS On the admission day, the last day of the fast and the day of refeeding, blood samples were collected at 10‐minute intervals from 0800 to 2000 h for determination of the LH pulse pattern. Daily determinations of immuno LH, FSH, oestradiol (E) and progesterone (P) were performed throughout the menstrual cycle in which the fast occurred.RESULTS Throughout the fasting days, the consistently low serum levels of glucose and insulin confirmed that all the subjects were fasting. However, in spite of profound metabolic changes and a significant loss of weight, the short‐term fast did not have discernible effects upon the reproductive hormones studied. Basal mean LH concentrations did not show any significant variation throughout the study period. The mean ± SEM number of LH pulses was 134 ± 1.5/12h on the control day, 12.4 ± 1.2/12h (NS) on the third day of fasting and 11 0 ± 1.5/12 h (NS) the day of refeeding. Each woman maintained a physiological pattern of LH, FSH, E and P throughout the menstrual cycle including the LH surge; ultrasound evidence of normal growth of a dominant follicle; and cycle length consistent with previous cycles.CONCLUSIONS Our results indicate that in spite of profound metabolic changes, a 72‐hour fast during the follicular phase does not affect the menstrual cycle of normal cycling women. It appears that the female reproductive axis during this phase of the cycle Is more resistant to an acute caloric deprivation than that of men or male monkeys.
Reduced lymphocyte β2‐adrenoceptor density and impaired diastolic left ventricular function in patients with glucocorticoid deficiency
Authors: Allolio Bruno , Ehses Wolfgang , Steffen Hans Michael , Müller Ralf 
Published: March 2008

SummaryOBJECTIVE Patients with adrenal crisis are at risk of severe hypotension not responding to administration of catecholamines. As glucocorticoids may be a prerequisite for intact β‐adrenoceptor function, impaired adrenoceptor activity may explain the hypotension and reduced cardiac performance in adrenal insufficiency. The aim of our study was, therefore, to further elucidate the permissive action of glucocorticoids on adrenergic function and cardiac performance.DESIGN Prospective randomized controlled study.PATIENTS Nine patients with adrenal insufficiency were investigated before and 48 hours after glucocorticoid withdrawal. Mineralocorticoid therapy remained unchanged during the study period.MEASUREMENTS Lymphocyte β2‐adrenoceptor density, intracellular c‐AMP response to isoprenaline, platelet α2‐receptor density, plasma catecholamines, serum Cortisol, plasma ACTH, echocardiography.RESULTS Glucocorticoid depletion was demonstrated by a fall in serum Cortisol from mean ± SEM 441 ± 62 to 45 ± 18 nmoI/I. Glucocorticoid withdrawal decreased lymphocyte β2‐receptor density from 798±111 to 498 ± 54 binding sites/cell (P<0.05) and the intracellular c‐AMP response to isoprenaline from 15.0 ± 4.2 to 8.2 ± 1.7 pmol/106 cells (P< 0.05). Echocardiography showed impaired diastolic relaxation after glucocorticoid withdrawal with prolongation of the rapid filling period (80.3 ± 12.5 vs 138.3 ± 11.8 ms, P < 0.05). Plasma catecholamines, platelet α2‐receptor density and systolic left ventricular function were not affected by glucocorticoid deficiency.CONCLUSIONS This study demonstrates the importance of normal glucocorticoid levels for β2‐adrenoceptor function and helps to explain the decreased responsiveness to catecholamines and the impaired cardiac performance in adrenal crisis.
17β‐Oestradiol counteracts the formation of the more acidic isoforms of follicle‐stimulating hormone and luteinizing hormone after menopause
Authors: Wide Leif , Naessén Tord 
Published: March 2008

SummaryOBJECTIVE When the gonadotropin levels increase at midcycle, more basic isoforms of FSH and LH appear in the circulation. However, when these gonadotrophins increase at menopause more acidic forms appear. The present study was done to see whether chronic 17β‐oestradiol (E2) administration to post‐menopausal women could counteract the formation of the more acidic isoforms after the menopause.DESIGN Serum samples were obtained from 16 postmenopausal women, mean age 70 years (range 63‐84 years), 46‐169 days after the subcutaneous insertion of a 20‐mg E2‐implant. FSH, LH and E2 in the sera were measured with fluoroimmunoassays. The median charge and the degree of charge heterogeneity of the FSH and LH isoforms were determined for each serum by electrophoresis in 01% agarose suspension. Sera from an age‐matched control group were analysed in parallel.RESULTS The E2 levels in the E2‐treated women were 230–570 pmoI/I, within the range expected during the midluteal phase of the normal menstrual cycle. The mean serum FSH and LH levels were similar to normal follicular phase FSH and LH levels (8 6 and 20 8% respectively of the control group). It was estimated that individual serum specimens from both groups contained 20–30 different isoforms for both FSH and LH. The median charges of the isoforms of FSH and LH were more basic in all the E2‐treated subjects than in their corresponding untreated controls. The mean median charge for FSH was close to the values for the follicular and luteal phases and that for LH close to that for the luteal phase. In some E2‐treated women the isoforms were even more basic with a charge similar to that at the midcycle peak. The degree of charge heterogeneity for the E2‐treated group was significantly (P<0.001) larger than for the controls and similar to that during the normal menstrual cycle.CONCLUSION Chronic E2 administration to post‐menopausal women counteracted the formation of more acidic isoforms of both FSH and LH after the menopause.
Effect of different treatment regimes on linear growth and final height in β‐thalassaemia major
Authors: De Sanctis Vincenzo , Katz Maurice , Vullo Calogero , Bagni Bruno , Ughi Monica , Wonke Beatrix 
Published: March 2008

SummaryOBJECTIVE The clinical picture of thalassaemia major has changed progressively over the years. Our study is a retrospective analysis of data on growth in a group of patients who have completed puberty spontaneously and have attained their adult height. Our objective was to evaluate the effect of different transfusion regimes and desferrioxamine administration on the growth pattern in β thalassaemia major.DESIGN AND PATIENTS We studied 64 patients (28 males and 36 females). The patients were divided into three groups (A, B and C) according to the different transfusion regimes and the schedules of chelating therapy. Group A consisted of 16 patients who were transfused regularly at low haemoglobin levels (on average 8 5 g/dl) from an early age and started subcutaneous chelation therapy during adolescence. Group B consisted of 19 patients who were transfused regularly at high haemoglobin levels (on average 10 g/dl) from an early age and started subcutaneous therapy during childhood. Group C consisted of 29 patients who were transfused regularly at high haemoglobin levels (on average 10‐5 g/dl) from an early age and started subcutaneous chelation therapy very early, at a mean age of 2 years. Standard auxological measurements were made at 3‐monthly intervals throughout childhood and puberty until adult height was achieved. For group C patients the data on linear growth are provided only until the age of 12 years.RESULTS Our study indicates that group A male and female patients did not grow significantly better than those in group B. Group C male and female patients, surprisingly, grew no faster than those who started chelation therapy late in childhood (group A). The most striking feature in the majority of both group A and B patients was reduced spurt in height at puberty. In addition, in both groups, a reduced sitting height due to spinal growth abnormality was found. An inverse correlation between sitting height and serum ferritin levels was observed in group A patients (r=–055, P<0 05), whereas there was a direct correlation in group B patients (r= 0 42, P< 0.05).CONCLUSIONS These data suggest that an ideal therapeutic regime has yet to be found which avoids the toxic effect of iron overload and on the other hand avoids interference with growth, secondary to desferrioxamine. Therefore we recommend that the growth of thalassaemia patients be monitored routinely at every follow‐up visit and documented on growth velocity charts in order to detect early changes in their growth pattern and to establish an appropriate protocol for investigation and treatment.
Hypothalamic‐pituitary ageing: progressive increase in FSH and LH concentrations throughout the reproductive life in regularly menstruating women*
Authors: Ebbiary N. A. Ahmed , Lenton E. A. , Cooke I. D. 
Published: March 2008

SummaryOBJECTIVE Reproductive ageing is associated with reduced fertility and endocrine changes that become more pronounced during the perimenopausal period. We aimed to assess changes in gonadotrophin concentrations and the onset of these changes during the reproductive life prior to the perimenopause.SUBJECTS Ovarian and pituitary hormones were measured and follicle growth monitored In 500 regularly cycling infertile women aged 20–44 years.MEASUREMENTS Serum levels of FSH and LH were determined during the follicular phase and ultrasonography was used to monitor follicle growth and ovulation. The luteal phase was assessed by sallvary progesterone measurements. Changes In basal FSH and LH with age during ovulatory cycles were assessed.RESULTS There was a significant progressive increase in FSH levels as early as age 29–30 years which was continued throughout the 30s and became more marked in the early 40s. LH levels showed significant Increase at the age of 35–36 years which was maintained till the age of 40 years and followed by a further increase in women aged > 40 years.CONCLUSION An increase in FSH and LH concentrations can be detected In women with regular ovulatory cycles quite early during the reproductive life. The Increase In basal FSH (and later LH) may represent the earliest endocrine marker of reproductive ageing. These age‐related increases in FSH and LH can be used as hormonal markers to counsel patients as to the likelihood of their reproductive potential.
Oestrogen formation in genital and non‐genital skin fibroblasts cultured from patients with hypospadias
Authors: Staib Peter , Kau Nikolaus , Romalo Gabriela , Schweikert Hans‐Udo 
Published: March 2008

SummaryOBJECTIVE Hypospadias is the most common birth defect in males. in most cases the aetiology is unknown. Since penile development is androgen dependent and oestrogen can modify androgen action, we compared the formation of oestrogen In penile tissue from patients with hypospadias to those with normal penile development.DESIGN AND PATIENTS Oestrogen formation was assessed in fibroblast monolayers grown from biopsies of genital and non‐genital skin from 11 males with normal genital development (controls) and 18 males with severe hypospadias utilizing the incorporation of tritium into H2O resulting from the aromatization of 1β‐3H‐androstenedione.RESULTS in paired fibroblast strains from genital and non‐genital skin of nine males with hypospadias, oestrogen formation was significantly (P < 0·025) lower In non‐genital skin. Rates of oestrogen formation were also higher in a subset of foreskins from subjects with hypospadias than In normal controls and the remaining hypospadias subjects. In addition, oestrogen formation in this subset of fibroblast strains from patients with hypospadias was markedly enhanced by incubation of Intact monolayers with either cholera toxin or forskolin, agents known to stimulate CAMP formation. Oestrogen formation in the remaining cell strains (controls and hypospadias) was also enhanced in most instances by cholera toxin and forskolin, although to a much lower degree. Thus, we identified in the hypospadias group a subgroup of fibroblast strains in which unstimulated and stimulated oestrogen formation was markedly higher than in other strains examined.CONCLUSIONS Since oestrogen can modify certain androgen effects within cells and since formation of the male genitalia during embryogenesis is mediated by androgens, elevated oestrogen formation in male genital tissue might be a causative factor of hypospadias in some Instances.
Effect of treatment on established osteoporosis in young women with amenorrhoea
Authors: Gulekli Bulent , Davies Melanie C. , Jacobs Howard S. 
Published: March 2008

SummaryBACKGROUND AND OBJECTIVE Amenorrhoea in women of reproductive age causes loss of bone mineral. This study assessed the effect of treatment of amenorrhoea on bone mineral density.DESIGN Serial measurements of bone mineral density were obtained in women receiving treatment for amenorrhoea.PATIENTS Eighty‐five women aged 17‐40 with a past or current history of amenorrhoea, from various causes, with median duration of 46.5 months (range 8 months‐21 years).MEASUREMENTS Bone mineral density in the lumbar spine was measured by dual‐energy X‐ray absorptlometry. RESULTS initial vertebral bone mineral density was low, mean 0·85 (SD 0·10) g/cm2. After an interval of 19·6 (SD 7·5) months on treatment there was a highly significant increase to 0·89 (SD 0·10) g/cm2 (P < 0·0005). This was equivalent to a gain in bone mass of 21% per year (95% confidence interval 1·5–2·8%). improvement was seen in ail diagnostic groups (except polycystic ovary syndrome) and with all types of therapy. We observed no difference in the response of previously untreated patients compared with those already on treatment, nor any change in response with increasing duration of treatment. No new fractures were reported during the study. CONCLUSIONS Bone mineral density in young women with amenorrhoea is improved by appropriate treatment, but recovery is not substantial. Hence early diagnosis and therapy is essentlal to prevent bone loss.
Suramin in adrenocortical cancer: limited efficacy and serious toxicity
Authors: Arlt Wiebke , Reincke Martin , Siekmann Lothar , WInkelmann Werner , Allolio Bruno 
Published: March 2008

SummaryOBJECTIVE No satisfactory treatment for adrenocortical carcinoma (ACC) is available. We investigated the efficacy and toxicity of suramin In the treatment of metastatic ACC since suramin has been recently reported to be active as a single agent therapy for patients with ACC and prostatic carcinoma.DESIGN We collected data on 9 patients with metastatic ACC treated with suramin in four centres in Germany between 1987 and 1992.PATIENTS Nine patients (5 women, 4 men; age range 32–67 years) were included. Biochemical evidence of steroid excess was found in 6/9, in three leading to clinical symptoms (hypertension, hyperglycaemla, hirsutism, gynaecomastia).MEASUREMENTS Tumour responses were assessed by radiological and biochemical evaluation. Other investigations included regular measurements of blood cell counts, coagulation, hepatic and renal function parameters, and serum suramin concentrations.RESULTS The patients received cumulative doses ranging from.2 to 30·2 g suramin over periods of 1–15 months. 3/9 achieved a partial response, 2/9 disease stabilization and 4/9 experienced progressive disease. Tumour responses were transient. Suramin treatment was without direct influence on steroid excess. Serious side‐effects included coagulopathy (6/9), thrombocytopenla (6/9), polyneuropathy (2/9) and allergic skin reactions (4/9); the death of two patients was possibly related to suramin therapy. Both toxicity and tumour response were strongly associated with serum level or cumulative dose of suramin.CONCLUSIONS (1) Suramin is of antineoplastic efficacy in the treatment of metastatic adrenocortical carcinoma. (2) The clinical use of suramln is limited by a narrow therapeutic window with the risk of serious and possibly lethal toxicity at one extreme, and loss of efficacy at the other. Strict monitoring of suramin serum levels is mandatory aiming at levels between 200 and 250mg/l. Suramin should not be considered as first‐line treatment for metastatic adrenocortical carcinoma. (3) To improve treatment options in adrenocortical carcinoma as well as for further investigation on the usefulness of suramin, controlled prospective trials are urgently needed.