bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pyridostigmine fails to increase either spontaneous or GHRH‐stimulated GH secretion during day or night in growth hormone‐insufficient children
Authors: Kirk J. M. W. , Ross R. J. M. , Trainer P. J. , Froud A. L. J. , Davies S. C. , Savage M. O. , Besser G. M. 
Published: March 2008

Summary
objective The aim of the study was to Investigate whether pyridostigmine, a cholinesterase Inhibitor which is thought to act at the hypothalamus to Inhibit somatostatin secretion, would augment spontaneous or GHRH‐stimulated serum GH levels In patients with GH‐insufficiency. DESIGN Oral pyridostigmine 60 mg or placebo was administered at the start of a 9‐h subcutaneous infusion of either GHRH (1–29)NH2 10 μg/kg/h or saline control. Studies were performed during the daytime (0900–1800 h) in five patients, and the night‐time (2100–0600 h) In a further five.
patients Ten short, pre‐pubertal children (aged 6–11 years; eight boys) with growth hormone Insufficiency were studied.
measures Blood for serum GH was sampled every 20 min, and analysed using the PULSAR program.
results The subcutaneous infusion of GHRH 10 μg/kg/h Increased mean serum GH levels (± SEM): by day 17.7(±6.8) vs placebo 2.2(±0.4) mU/I (p>0.01), and by night 26.9(± 3.3) vs 5.5(± 1.3) mU/I (p > 0.05). There was a significant rise In mean ‘baseline’ GH concentration: by day 5.5(±1.7) vs 1.0(±0.0) mU/I (p>0.05); and night 8.2(±2.7) vs 1.3(±0.3) mU/I (p>0.05). Pyridostigmine failed to produce a significant overall increase In either spontaneous or GHRH‐stimulated GH secretion by day or night, although there was a significant rise In mean GH levels during the 3 h following pyridostigmine administration In the morning: 4.4(±1.1) vs 2.4(±0.5) mU/I (p>0.001). GHRH or pyridostigmine given singly or in combination had no significant effect on the number of pulses. Side‐effects attributable to pyridostigmine occurred in seven children.
conclusions Pyridostigmine, either on Its own or as an adjuvant therapy In combination with GHRH, acts for only a brief time and does not offer any potential benefit In the management of children with short stature.
Effect of ritanserin, specific 5HT–2 antagonist, on PRL secretion in normal subjects and in different hyperprolactinaemic conditions*
Authors: Falaschi P. , Rosa M. , Rocco A. , D'Urso R. , Proletti A. , Melts G. B. 
Published: March 2008

SUMMARYThe availability of a new specific anti 5HT–2 compound, ritanserin (RTS), led us to further investigate the role of serotonin in controlling PRL secretion. The drug was administered to normoprolactinaemic subjects and to patients with differing hyperprolactinaemic conditions. While RTS failed to modify PRL levels in normoprolactinaemic subjects and in patients with PRL‐secreting pituitary adenomas, a marked decrease in the hormone was obtained in patients with functional and puerperal hyperprolactinaemia. The lack of effect of RTS in PRL‐secreting pituitary adenomas suggests that the reported suppression of PRL by other antiserotoninergic drugs, such as metergoline, is probably due to their concomitant dopamlnergic activity
The presence of cation‐dependent proteases for insulin‐like growth factor binding proteins does not alter the size distribution of insulin‐like growth factors in pregnancy
Authors: Davies S. C. , Holly J. M. P. , Coulson V. J. , Cotterill A. M. , Abdulla A. F. , Whlttakert P. G. , Chard T. , Wass J. A. H. 
Published: March 2008

SUMMARY objective The aim was to Investigate the sera of pregnant women for the presence of specific proteases for insulin‐like growth factor binding proteins (IGFBPs) and to determine the effect of these on the distribution of IGFs in the circulation design The method used was the chromatographic and electrophoretic analysis of patients’ serum
patients Sera were examined from normal women during pregnancy: first trimester (n=4), second trimester (n= 4) and third trimester (n= 10). Eight women with Type I diabetes in the third trimester were also studied along with sera from ten normal adult volunteers. measurements Circulating IGF‐I and IGF‐II levels were measured by RIA and their distribution examined by gel filtration. The pattern and stability of the IGFBPs was Investigated by Western Iigand blotting results A marked reduction in the serum levels of IGFBP‐2, IGFBP‐3 and IGFBP‐4 on Western Iigand blotting, which was associated with the presence of three Independent, cation‐dependent proteases that were specific for different IGFBPs, was found in late pregnancy. Gel filtration of third trimester serum revealed most of the IGF‐I to be present in a complex larger than 130 kDa, with a similar distribution to that found in serum of non‐pregnant women. The enzymatic modification of the binding proteins made apparent by the decrease in binding protein bands on Western Iigand blotting of preincubated samples had no effect on the distribution of IGF‐I following size ractionation conclusions There appear to be at least three Independent enzymes that are Induced or activated during pregnancy to modify IGFBP‐2, IGFBP‐3 and IGFBP‐4 sufficiently to prevent their detection by Iigand blotting. However, this enzymatic processing does not alter the distribution of IGFs, suggesting that the altered binding proteins are still able to carry IGFs but with reduced affinity. Such an alteration in the carrying mechanism of IGFs may have profound effects upon the bioavailability of the IGFs to the maternal tissues and contribute to the altered metabolic demands of pregnancy
The effect of growth hormone (GH) therapy on urinary pyridinoline cross‐links in GH‐deficient adults
Authors: Schlemmer Annette , Johansen Julia S. , Pedersen Saren A. , Jargensen Jens O. L. , Hassager Christian , Christiansen Glaus 
Published: March 2008

SUMMARY objective The aim was to study the effect of growth hormone (GH) on new markers of bone resorption (fasting urinary excretion of pyridinium cross‐links (pyridinoline and deoxypyrWlnoline)) in GH‐deficient adults design Randomized, double‐blind, placebo‐controlled cross‐over study. The treatment periods (GH 2 IU/in2 subcutaneously, or placebo daity for 4 months) were separated by a 4‐month washout period. patients Twenty GH‐deficient adults (aged 18–39) measurements Blood and fasting urine samples were collected at the end of each 4‐month treatment period. Plasma bone Gla protein was measured by radioimmunoassay and urine pyridinoline and deoxypyrfdinoline were measured by spectrofluorometry after high performance liquid chromatography and corrected for urinary creatinine results GH increased fasting urinary excretion of pyridinoline (287 ± 123%, P > 0·001) and deoxypyridinoline (313 ± 140%, P > 0·001). The GH‐induced Increment In these parameters correlated with the increase seen in plasma bone Gla protein (r= 0·83–0·86, P > 0·001). conclusion Four months of GH substitution in GH‐deficient adults increases bone resorption as well as bone formation. The effect on bone mass has yet to be assessed
Insulin secretion, insulin sensitivity and glucose‐mediated glucose disposal in Cushing's disease: a minimal model analysis
Authors: Page Renee , Boolell Mltra , Kalfas Anna , Sawyer Steven , Pestell R. , Ward Glenn , Alford Frank 
Published: March 2008

SUMMARY objective We wished to assess the contributions of Insulin secretion, insulin sensitivity and glucose‐mediated glucose disposal to glucose tolerance in subjects exposed to chronic glucocorticoid excess. DESIGN Patients with Cushing's disease were subjected to a frequently sampled intravenous glucose tolerance test before and at least 3 months after curative surgery and compared to a control group patients Seven patients with clinical and biochemically proven pituitary dependent Cushing's disease and 10 healthy control subjects were studied measurements Paired glucose and insulin plasma profiles were analysed by the Minimal Model method of Bergman, which provided simultaneous estimates of the glucose decay rate, Insulin secretion, insulin sensitivity and glucose‐mediated and non‐insulin‐mediated glucose disposal. Data were evaluated by non‐parametric statistical analysis and reported as median and interquartile ranges results Basal glucose, insulin, C‐peptlde and glucagon levels were significantly raised preoperatively and fell towards normal post‐operatlvely. Glucose tolerance assessed as glucose decay rate was reduced significantly preoperatively (pre: 1·3 (0·8–2·0) vs post: 1·6 (1·5–2·6) per min x 102, p > 0·05). First phase insulin release was similar in the Cushing's disease and control subjects. In contrast, second phase insulin release was significantly greater preoperatively and remained high post‐operatlvely compared to control subjects (pre: 18·8 (16·7–23·6) vs post: 16·7 (8·5–18·8) vs control 11·1 (4·5–15·4) mU/g/min2 x 10‐2, P > 0·002). Median insulin sensitivity was reduced by 60% preoperatively in the Cushing's disease subjects compared to the post‐operative Cushing's disease and control subjects (pre: 2·1 (1·3–4·2) vs post: 5·0 (3·2–7·3) vs control 5·1 (2·2–7·2) per min/mU/l x 104). Median glucose‐mediated glucose disposal was reduced by 40% In the pre and post‐operative Cushing's disease subjects compared to the control group (pre: 1·1 (0·6–2·1) vs post: 1·1 (0·6–2·1) vs control 1·9 (1·4–2·6) per min x 102), but this was not statistically significant. However, non‐insulin‐mediated glucose disposal was significantly reduced In the preoper‐atlve Cushing's disease subjects (pre: 0·55 (0·08–1·59) vs control 1·43 (0·94–2·27) per min x 102, p > 0·05). In the Cushing's disease subjects, glucose tolerance correlated with both Insulin sensitivity (rs= 0·84, P > 0·01) and non‐insulin‐mediated glucose disposal (rs= 0·56, P > 0·05). The fractional clearance rate of insulin was unaltered by Cushing's disease. conclusions Cushing's disease subjects are characterized by impaired glucose tolerance due to both reduced insulin sensitivity and non‐fnsulln‐mediated glucose disposal, In the presence of enhanced Insulin secretion
Serum thyroglobulin measurements in thyroid cancer: evaluation of‘false’ positive results
Authors: Black E. G. , Sheppard M. C. 
Published: March 2008

SUMMARY objective Serum thyroglobulin (Tg) should be undetectable in patients successfully treated for thyroid carcinoma. We have examined the course of disease in 19 patients with raised serum Tg (< 5 μ g/l) on initial measurement but no other evidence of residual, recurrent or metastatic cancer. design 416 patients from several centres were followed for periods between 1 and 9 years. Serum Tg was measured at 6–12‐month intervals patients All had differentiated thyroid cancer, treated by partial or total thyroldectomy and/or 131I ablation, and were receiving suppressive thyroxine therapy. measurement Serum Tg was measured and clinical, X‐ray and scan assessment made of presence or absence of residual, recurrent or metastatlc cancer results Of 416 patients initially assessed, only 19 had Tg < 5 μ g/l but no clinical or radiological evidence of disease. At follow‐up, 11 patients had developed overt signs of malignancy; one had been treated with 131I with a subsequent fall in Tg; five had Tg between 5 and 20 μ g/l with incompletely suppressed TSH levels; two subjects remained with slightly elevated Tg and undetectable TSH. conclusion Patients with elevated Tg require careful follow‐up even in the apparent absence of disease. Moderate elevation of serum Tg may be due to inadequate thyroxine suppression therapy, assessed by detectable TSH values measured in a sensitive assay
Androgen dependent stimulation of aromatase activity in genital skin fibroblasts from normals and patients with androgen insensitivity
Authors: Stlllman S. C. , Evans B. A. J. , Hughes I. A. 
Published: March 2008

SUMMARY objective To measure the effect of androgens or aromatase activity as an index of androgen responsiveness in patients with androgen insensitivity design Genital skin fibroblasts were established in culture using primary skin explants obtained from normal males at the time of circumcision and from androgen insensitive patients who had surgery either for gonadectomy (complete androgen insensitivity syndrome) or for reconstruction of the external genitalia (partial androgen insensitivity syndrome) patients Foreskin samples were obtained at the time of circumcision in 27 normal males. Scrotal or labla majora skin was obtained at the time of surgery from 14 patients with the complete and 22 with the partial forms of the androgen insensitivity syndrome measurements Basal and stimulated levels of aromatase activity were measured in genital skin fibroblasts following preincubation with natural and synthetic, non‐metabolizable androgens results Following a 48‐hour preincubation with testosterone or dihydrotestosterone, there was a five to six‐fold stimulation of aromatase activity in normal fibroblasts. Mibolerone, a synthetic androgen, produced similar results. The stimulatory effect was blocked by anti‐androgens. Seven patients with partial androgen insensitivity, of whom four were either receptor deficient or showed a qualitative defect in androgen binding, had reduced mibolerone induced stimulation of aromatase activity. All ten patients with receptor negative complete androgen insensitivity had an absent response. There was no aromatase induction in a further three patients with complete androgen insensitivity who were receptor positive. Two siblings in the latter group had an exon deletion encoding for part of the DNA binding domain of the androgen receptor conclusions Androgens stimulate aromatase activity in genital skin fibroblasts from normals. The response is mediated via the androgen receptor and can be decreased or absent in patients with the androgen insensitivity syndrome. This may be a useful in‐vitro marker of androgen responsiveness in such patients
The relationship between growth hormone (GH) messenger ribonucleic acid levels and hormone release from individual cells derived from human GH‐secreting pituitary adenomas
Authors: Hofland L. J. , Velkeniers B. , van Koetsveld P. M. , Hooghe‐Peters E. L. , Lamberts S. W. J. 
Published: March 2008

SUMMARYGH mRNA expression and GH release by Individual cells derived from four GH‐secreting pituitary adenomas were studied by in‐situ hybridization and the reverse haemolytic plaque assay, respectively. In addition the percentage of PRL mRNA‐containing cells was determined in these cell suspensions. The percentages of GH mRNA‐containing cells varied between 52 and 89 while the percentages of GH plaque forming cells varied between 25 and 77. Frequency distributions of GH mRNA levels in individual cells and of individual GH plaque areas showed a majority of the cells having low GH mRNA levels and secreting low amounts of GH respectively, while there is a low proportion of cells expressing high GH mRNA levels and forming large GH plaques. There was a significant correlation between the GH mRNA levels and the GH plaque areas of individual cells from the four adenomas (P > 0.001). The percentages of PRL mRNA‐containing cells in the four different adenomas amounted to > 1, 5, 2 and 18. Cultured cells from the adenomas consisting of 5 and 18|X% PRL mRNA‐containing cells also contained and released measurable amounts of PRL. Our data show that Individual cells from GH‐secreting pituitary adenomas are heterogeneous with respect to GH mRNA expression, a small proportion of the cells expressing a high amount of GH mRNA. The heterogeneity in GH mRNA expression is correlated with the heterogeneity In GH release. These observations suggest that a considerable part of GH secreted from a GH‐secreting pituitary adenoma is produced by a minority of the GH‐secreting tumour cell population. This might be a basis for the disappointing degree of tumour shrinkage which is observed in most acromegalic patients treated with the somatostatin analogue SMS 201–995.
The relationship between sex steroids and bone mineral content in women soon after the menopause
Authors: Spector T. D. , Thompson P. W. , Perry L. A. , McGarrigle H. H. , Edwards A. C. 
Published: March 2008

SUMMARYPrevention of postmenopausal osteoporosis is now possible with current therapy, if initiated soon after the menopause and continued for at least 10 years. Simple ways of detecting those at risk of subsequent osteoporosis are urgently needed. This study investigated the hypothesis that certain serum sex hormones could predict bone mineral content (BMC) as measured by dual photon densitometry, soon after the menopause. The subjects included 136 healthy white females within 30 months of their last menstrual period with a mean age of 52 years. Of the sex hormones, the adrenal androgen dehydroeplan‐drosterone sulphate (DHEAS) correlated best with spinal BMC, a relationship which was significant using multiple regression (P = 0.02), although the correlation was weak (r =+0.19). A direct physiological role for DHEAS has yet to be found, despite being present in large quantities in serum, although it may act as a marker for other processes. No association was seen between testosterone, sex hormone binding globulin, oestradiol, oestrone and oestrone sulphate and spinal BMC. No significant correlations with any hormones were seen with femoral BMC. The data suggest that serum sex hormones are not useful markers of current bone mineral status soon after the menopause, although further work is needed to explore the relationship with DHEAS
Corticotrophin releasing hormone (CRH1–41) stimulates the secretion of adrenocorticotrophin, vasopressin and oxytocin but not adrenocorticotrophin precursors: evidence from petrosal sinus sampling in man
Authors: Nussey S. S. , Page S. R. , Peterson D. B. , Byrne J. , Crosby S. R. , White A. , Ang V. T. Y. , Jackson R. , Jenkins J. S. 
Published: March 2008

SUMMARYTo examine the relationship between corticotrophin releasing hormone (CRH), arginine vasopressin (AVP) and oxytocin (OXT) we have studied the responses of adenohypophyseal and neurohypophyseal hormones to CRH in eight patients (age 26–64 years, six female) with suspected pituitary‐dependent Cushing's syndrome during bilateral, simultaneous inferior petrosal sinus catheterization. Blood samples were taken from both petrosal sinuses and a peripheral vein before, and at 5‐min intervals for 15 min after, an intravenous injection of 100 μg human CRH1–41. CRH increased sinus AVP concentrations in all eight patients and OXT concentrations in four of five patients studied. Although AVP concentrations often increased in both sinuses, the side of maximal AVP rise was termed sidemax‐AVP. CRH did not affect peripheral or petrosal sinus mean concentrations of LH, FSH, GH or TSH. While there was no change in mean peripheral concentrations of AVP, OXT, ACTH, ACTH precursors or prolactin after CRH, sinus concentrations of OXT, ACTH and prolactin on sidemax‐AVP were markedly elevated over contralateral values. CRH did not increase mean sinus concentrations of ACTH precursors. In seven patients with either no radiological abnormality of the pituitary fossa or a small adenoma the mean ACTH precursor/ACTH ratio in blood sampled from all sites was 2.1 |Mp 0.16 (mean |Mp SEM, n = 50). In a patient with a large, locally invasive tumour the mean ACTH precursor/ACTH molar ratio was 32.1 |Mp 1.3 (n = 12; P > 0.001), suggesting that alterations in this molar ratio may reflect the biological properties of the tumour. The source of CRH‐stimulatable AVP and OXT remains uncertain. While it is recognized that the data were accumulated in patients with pathology of the hypothalamo—hypophyseal—adrenal axis, these observations suggest a novel relationship between AVP, OXT and CRH in the regulation of ACTH secretion in man. We suggest that the relation between plasma AVP and corticosteroids seen in clinical hypoadrenal states could be explained by chronic stimulation of AVP secretion by CRH.
Genetic differences shown by HLA typing among Japanese patients with euthyroid Graves' ophthalmopathy, Graves' disease and Hashimoto's thyroiditis: genetic characteristics of euthyroid Graves' ophthalmopathy
Authors: Inoue Daisuke , Sato Kaoru , Maeda Masahiro , Inoko Hidetoshi , Tsuji Kimiyoshi , Mori Toru , Imura Hiroo 
Published: March 2008

SUMMARYEuthyroid Graves' ophthalmopathy (EO) is an ophthalmic disorder without persistent hyperthyroidism. To elucidate genetic differences among EO, Graves' disease (Gr) and Hashimoto's thyroiditis (H), we analysed HLA‐A, B, C, DR, DO, D and DP types in 23 Japanese EO patients, 88 Gr patients, 46 H patients and 186 control subjects utilizing assays of lymphocyte cytotoxicity and restriction fragment length polymorphism (RFLP). When compared with the control subjects, EO patients showed significant associations with HLA B40 (w61), DR9, DQw3, and Dw15 (P > 0.01) and with HLA B12 and Cw1 (P > 0.05). When allowance was made for the number of antigens tested, only DQw3 was significant. Significant differences were found between EO and Gr (DPw2), and between EO and H (Cw1) even after correction of P values. Comparisons between EO and related subgroups of Gr confirmed the heterogeneity of EO again. It is concluded from these results that EO is associated with different HLA types from Gr and H.
Prevalence and follow‐up of abnormal thyrotrophin (TSH) concentrations in the elderly in the United Kingdom
Authors: Fade J. V. , Franklyn J. A. , Cross K. W. , Jones S. C. , Sheppard M. C. 
Published: March 2008

SUMMARYIncreasing use of assays for TSH with improved sensitivity as a first‐line test of thyroid function has raised questions regarding prevalence and clinical significance of abnormal results, especially values below normal. We have assessed the thyroid status of 1210 patients aged over 60 registered with a single general practice by measurement of serum TSH using a sensitive assay. High TSH values were more common in females (11.6|X%) than males (2.9|X%). TSH values below normal were present in 6.3|X% of females and 5.5|X% of males, with values below the limit of detection of the assay present in 1.5|X% of females and 1.4|X% of males. Anti‐thyroid antibodies were found in 60|X% of those with high TSH but only 5.6|X% of those with subnormal TSH. Eighteen patients were hypothyroid (high TSH, low free thyroxine) and one thyrotoxic (low TSH, raised free thyroxine) at initial testing. Seventy‐three patients with elevated TSH but normal free T4 were followed for 12 months; 13 (17.8|X%) developed low free T4 levels and commenced thyroxine, TSH returned to normal in four (5.5|X%) and 56 (76.7|X%) continued to have high TSH values. Sixty‐six patients with TSH results below normal were followed. Of the 50 subjects with low but detectable TSH at initial testing, 38 (76|X%) returned to normal at 12 months; of those 16 with undetectable TSH followed, 14 (87.5|X%) remained low at 12 months. Only one subject (who had an undetectable TSH) developed thyrotoxicosis. In view of the marked prevalence of thyroid dysfunction in the elderly, we suggest that screening of all patients over 60 should be considered. It is important that those with high TSH are followed in view of the risk of progression to overt hypothyroidism, but the risk of thyrotoxicosis in those with TSH values below normal appears small.