bluuebunny/crossref_metadata_2025_split huggingface dataset:
Insulin‐like growth factor (IGF)‐1 and IGF‐binding protein‐1 concentrations in serum of normal subjects after alcohol ingestion: evidence for decreased IGF‐1 bioavailability
Authors: Röjdmark  , Rydvald  , Aquilonius  , Brismar  
Published: March 2003

OBJECTIVEBoth insulin‐like growth factor (IGF)‐1 and insulin‐like growth factor‐binding protein (IGFBP)‐1 are synthesized by the liver. It is well known that chronic alcohol abuse impairs liver function, but less is known about how an acute intake of moderate quantities of alcohol affects hepatic production of IGF‐1 and IGFBP‐1. The objective of the present investigation was to study this issue by measuring serum levels of IGF‐1 and IGFBP‐1 in normal subjects before, during and after ingestion of a moderate dose of ethanol.SUBJECTS AND DESIGNEight healthy subjects were tested on two occasions. On one occasion (experiment A), three 150‐ml doses of ordinary drinking‐water were given at 08.00, 09.30, and 11.00 h. On another occasion (experiment B), three 150‐ml drinks of diluted ethanol were given instead of water. Each drink contained 0.45 g ethanol/kg b.w. Experiments A and B were performed in random order, 1 week apart. Blood samples were collected before, during and after the drinks over a period of 7 h (08.00–15.00 h). One blood sample was also drawn at 08.00 h the following day.MEASUREMENTSBlood glucose and serum concentrations of ethanol, insulin, growth hormone (GH), IGF‐1 and IGFBP‐1 were determined.RESULTSWhen alcohol had been ingested, the serum ethanol concentration rose to a peak value of 28.6 ± 0.9 mmol/l (mean ± SEM). The serum IGF‐1 level declined significantly toward the end of the 7‐h period. The serum IGFBP‐1 level increased promptly in response to ethanol, and reached a maximum 2.7 times above basal as the ethanol level peaked. Neither IGF‐1, nor IGFBP‐1 levels changed significantly after water intake. The IGF‐1 : IGFBP‐1 ratio declined markedly after ethanol (from 15.7 ± 3.9 to 3.9 ± 0.6; P < 0.01), but not after water intake. The blood glucose and serum levels of insulin and GH were unaffected by both ethanol and water.CONCLUSIONSIngestion of moderate amounts of alcohol by healthy individuals results in an acute and profound increase in the serum IGFBP‐1 level and a protracted and less powerful decline in the IGF‐1 level. The mechanism behind the IGFBP‐1 increase is probably a direct effect on the liver, since neither insulin, nor glucose or GH concentrations changed significantly in response to the ethanol challenge.
Vitamin D receptor gene polymorphisms influence susceptibility to type 1 diabetes mellitus in the Taiwanese population
Authors: Chang Tien‐Jyun , Lei Hsien‐Hsien , Yeh Jih‐I , Chiu Ken C. , Lee Kuan‐Ching , Chen Mei‐Chu , Tai Tong‐Yuan , Chuang Lee‐Ming 
Published: March 2003

OBJECTIVEVitamin D and its receptor have been suggested to play a role in the pathogenesis of type 1 diabetes mellitus. We have therefore studied the influence of vitamin D receptor (VDR) gene polymorphisms on susceptibility to type 1 diabetes, and rates of glutamic acid decarboxylase (GAD65) autoantibody and islet cell autoantibody (ICA512) positivity.SUBJECTSAND MEASUREMENTS One hundred and fifty‐seven type 1 diabetic patients and 248 unrelated normal controls were recruited for this study. Genomic DNA was extracted from peripheral blood leucocytes. All type 1 diabetic patients and controls were genotyped using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP), for three restriction sites in the VDR gene, BsmI, ApaI and TaqI. The χ2 test was used to compare the frequency of the VDR gene polymorphisms in patients and normal controls. The association of VDR gene polymorphisms in type 1 diabetes with the presence of GAD65 and ICA512 autoantibodieswere also examined using the χ2 test.RESULTSThe allele frequency of the BsmI and ApaI polymorphisms, but not TaqI polymorphism, differed between patients and controls (BsmI P = 0.015; ApaI P = 0.018; TaqI P = 0.266). However, after correction for the three different polymorphisms tested, only the BsmI was significant (pc = 0.045).CONCLUSIONSVitamin D receptor gene polymorphisms were associated with type 1 diabetes in a Taiwanese population. However, functional studies are needed to establish the role of the vitamin D receptor in the pathogenesis of type 1 diabetes mellitus.
Establishment of reference values for standard dose short synacthen test (250 μg), low dose short synacthen test (1 μg) and insulin tolerance test for assessment of the hypothalamo–pituitary–adrenal axis in normal subjects
Authors: Gonzálbez  , Villabona  , Ramón  , Navarro  , Giménez  , Ricart  , Soler  
Published: March 2003

OBJECTIVETo assess the integrity of the hypothalamo–pituitary–adrenal(HPA) axis, many authors have proposed the short synacthen test (ACTH1–24, Tetracosactrin) as a replacement for the insulin tolerance test (ITT). The aim of this study was to compare the plasma cortisol response obtained with both short synacthen tests (high dose (HDT, 250 μg) and low dose (LDT, 1 μg)) with the peak reached during the ITT in healthy volunteers, and to establish the plasma cortisol cut‐off level in each test.SUBJECTS AND METHODSThirty healthy subjects (16 F, 14 M), mean age 34 years, underwent both short synacthen tests. Twenty healthy subjects, 15 of whom (11 F, nine M) belonged to the above group, mean age 30 years, underwent an ITT. Plasma cortisol was measured using a chemiluminiscence immunoassay.RESULTSThere were no differences between plasma cortisol 30 minutes after both short synacthen tests (HDT: 684 ± 123, LDT: 669 ± 119 nmol/l) and the peaks reached with the LDT (691 ± 123 nmol/l) and the ITT (673 ± 99 nmol/l).The only difference (P < 0.001) was found in the comparison of plasma cortisol peak reached with the HDT (802 ± 142 nmol/l) with the other tests. Plasma cortisol levels obtained in the 5th percentile in each test were: at + 30 minutes: (HDT: 537, LDT: 489 nmol/l), peak: (HDT 649, LDT 498, ITT: 539 nmol/l).CONCLUSIONSComparison of the plasma cortisol response at + 30 minutes with both short ACTH tests and the peak in the insulin tolerance test did not reveal differences. Each test, for each time point and for each biochemical method, requires its own minimum threshold of normality to assess the hypothalamo–pituitary–adrenal axis.
Androgens and penile erection: evidence for a direct relationship between free testosterone and cavernous vasodilation in men with erectile dysfunction
Authors: Aversa A. , Isidori A. M. , De Martino M. U. , Caprio M. , Fabbrini E. , Rocchietti‐March M. , Frajese G. , Fabbri A. 
Published: March 2003

OBJECTIVEAndrogens are essential in the maintenance of nitric oxide‐mediated erectile activity in the rat. The objective of the present study was to investigate the role of androgens in regulating trabecular smooth muscle relaxation in the corpus cavernosum in response to vasoactive challenge in men with erectile dysfunction (ED).DESIGNRetrospective, double‐blind correlation analyses.PATIENTSFifty‐two impotent patients without confounding risk factors for ED were obtained from a total of 250 undergoing diagnostic evaluation.MEASUREMENTSAll patients had dynamic colour duplex ultrasound (D‐CDU) and hormonal evaluation for LH, total and free testosterone, SHBG and oestradiol.RESULTSBased upon D‐CDU results patients were diagnosed as having arteriogenic (AR, n = 18; mean age 51) or corporeal venocclusive (CVO, n = 13; mean age 49) ED; in other patients (n = 21, mean age 43) a diagnosis of psychogenic (P)‐ED was made by comprehensive psychogenic testing and confirmed by normal D‐CDU results. AR and CVO patients had altered compliance of cavernous arteries recorded by D‐CDU [20–25% lower resistive index (RI) than patients with psychogenic ED], and lower free testosterone (FT) levels than psychogenic patients [42.3 ± 3.5 SE and 49.3 ± 5.2 vs. 75.2 ± 7.6 pmol/l, respectively; P < 0.01]. More important, in all patients there was a strong direct correlation between resistive index values and FT levels (r = 0.47, P = 0.002); the relationship was maintained also when adjusted for age, SHBG and oestradiol (r = 0.37, P = 0.02).CONCLUSIONSThese results indicate that in men with erectile dysfuntion low free testosterone may correlate independently of age with the impaired relaxation of cavernous endothelial and corporeal smooth muscle cells to a vasoactive challenge. These findings give clinical support to the experimental knowledge of the importance of androgens in regulating smooth muscle function in the penis.
Tall stature in familial glucocorticoid deficiency
Authors: Elias Lucila L. K. , Huebner Angela , Metherell Louise A. , Canas Atilio , Warne Gary L. , Bitti Maria L Manca , Cianfarani Stefano , Clayton Peter E. , Savage Martin O. , Clark Adrian J. L. 
Published: March 2003

OBJECTIVEFamilial glucocorticoid deficiency (FGD) has frequently been associated with tall stature in affected individuals. The clinical, biochemical and genetic features of five such patients were studied with the aim of clarifying the underlying mechanisms of excessive growth in these patients.PATIENTS AND METHODSFive patients with a clinical diagnosis of FGD are described in whom the disorder resulted from a variety of novel or previously described missense or nonsense mutations of the ACTH receptor (MC2‐R). All patients demonstrated excessive linear growth over that predicted from parental indices and increased head circumference.RESULTSGrowth hormone and IGF‐I‐values were normal. Growth charts suggest that the excessive growth is reduced to normal following the introduction of glucocorticoid replacement. A characteristic facial appearance including hypertelorism, marked epicanthic folds and prominent frontal bossing was noted.CONCLUSIONSThese findings indicate that ACTH resistance resulting from a defective ACTH receptor may be associated with abnormalities of cartilage and/or bone growth independently of the GH–IGF‐I axis, but probably dependent on ACTH actions through other melanocortin receptors.
Sweat secretion rates in growth hormone disorders
Authors: Sneppen Simone B. , Main Katharina M. , Juul Anders , Pedersen Lone M. , Kristensen Lars Ø. , Skakkebæk Niels E. , Feldt‐Rasmussen Ulla 
Published: March 2003

BACKGROUNDWhile increased sweating is a prominent symptom in patients with active acromegaly, reduced sweating is gaining status as part of the growth hormone deficiency (GHD) syndrome.DESIGN AND SUBJECTSSweat secretion rate (SSR), as measured by pilocarpine iontophoresis represents the maximal capacity for stimulated sweat secretion in a localized skin area. SSR was studied in 37 patients with a history of acromegaly, 20 adult patients with GHD before and during long‐term GH substitution of GHD adults, and 58 control subjects.RESULTSAcromegaly: Patients with acromegaly had significantly higher SSR than healthy controls (Z‐score + 1.9 (± 1.1) mean (± SD) (P < 0.001)). SSR was increased irrespective of current clinical disease activity. Thus, the SSR Z‐scores in 16 clinically inactive patients were + 2.1 (± 1.2), in 10 slightly or doubtfully active patients + 1.5 (± 0.7) and in 11 active patients + 1.8 (± 1.3). There was no correlation between SSR and IGF‐I. GHD: Twenty adult patients participated in an 18‐month randomised, placebo controlled, double blinded study of physiological dose GH substitution, followed by 18 months of open GH treatment. SSR at baseline was reduced in male but not in female GHD patients. Mean SSR (95% confidence interval) for 11 male patients was 89.0 mg/30 minutes (51.9–126.1) as compared to 133.5 mg/30 minutes (59.2–259.9) (P = 0.01) in 24 male controls, and for 11 female patients 48.2 mg/30 minutes (25.9–70.6) as compared to 49.2 mg/30 minutes (12.6–93.9) in 34 female controls. GH treatment in physiological substitution doses for up to 36 months had no effect on SSR.CONCLUSIONWe have demonstrated that longstanding GH hypersecretion in patients with acromegaly induces irreversible changes of sweat gland function, with persistently elevated SSR despite treatment and clinical cure. In GHD patients, SSR was reduced in males but not in females, which together with the established gender difference in normal controls emphasises the role of androgen deficiency as a cofactor for reduced sweating in hypopituitary patients. Sweat gland development seems to be more susceptible to lack of hormones in childhood and adolescence than in adulthood, whereas growth hormone excess can modify sweat function later in life.
Serum α‐subunit levels in patients with pituitary adenomas
Authors: Samejima Naoyuki , Yamada Shozo , Takada Koji , Sano Toshiaki , Ozawa Yasunori , Shimizu Taeko , Usui Masaaki , Shishiba Yoshimasa 
Published: March 2003

OBJECTIVE We investigated preoperative and postoperative serum α‐subunit levels and the α‐subunit response to TRH in patients with various types of pituitary tumour and correlated the data with histological findings in order to clarify the significance of α‐subunit measurement in pituitary adenomas.PATIENTS We examined 59 patients with pituitary tumours (22 with GH cell adenomas, 30 with clinically nonfunctioning adenomas and seven with other tumours) treated at Toranomon Hospital between 1996 and 1998.RESULTS The basal α‐subunit level was supranormal in six out of 22 (27%) patients with a GH cell adenoma and in nine out of 30 (30%) patients with a nonfunctioning adenoma. A paradoxical α‐subunit response to TRH was found in seven out of 22 (32%) patients with a GH cell adenoma. These seven patients also showed a paradoxical GH response to TRH administration. In addition, paradoxical response to TRH was found in eight out of 30 (27%) patients with a clinically nonfunctioning adenoma. In contrast, patients with other types of pituitary tumour showed neither a supranormal α‐subunit level nor a paradoxical response to TRH. The supranormal α‐subunit level and the abnormal response to TRH were normalized in both GH cell adenoma and nonfunctioning adenoma patients after successful surgery. Immunohistochemical studies showed α‐subunit positive cells in 51% of GH cell adenomas or nonfunctioning adenomas and there was a good concordance with the serum α‐subunit levels in both GH cell adenoma and nonfunctioning adenoma patients.CONCLUSIONS These findings suggest that supranormal serum α‐subunit levels are mainly due to hypersecretion by the tumour itself, while the paradoxical α‐subunit response to TRH is an associated phenomenon in patients with a GH cell adenoma or nonfunctioning adenoma. The α‐subunit level and the response to TRH may be useful indicators for assessing the operative outcome, especially in nonfunctioning adenoma patients who have no other definite endocrine markers.
Choosing an oestrogen replacement therapy in young adult women with Turner syndrome*
Authors: Guttmann Hadassah , Weiner Zeev , Nikolski Eugenia , Ish‐Shalom Sophia , Itskovitz‐Eldor Joseph , Aviram Michael , Reisner Shimon , Hochberg Ze'ev 
Published: March 2003

OBJECTIVE Hormone replacement therapy (HRT) is prescribed to most patients with Turner syndrome (TS) although its use in adult TS patients has not been scientifically evaluated. The present study was performed to compare the short‐term effects in adult women with Turner syndrome of low‐dose oral conjugated oestrogen (0·625 mg, CE) with relatively high dose ethinyl oestradiol (30 µg, EE2); both combined with an oral progestin.DESIGN and PATIENTS After 4 months off HRT, 17 young, otherwise healthy women with TS were enrolled in a random, unblinded, crossover study of the two oestrogenic preparations, each given for 6 months.MEASUREMENTS We compared parameters of oestrogenic activity that would cover immediate changes in hormone levels, biochemistry, bone turnover, uterine and cardiac variables, which constitute risk factors for later development of diabetes, atherosclerosis, osteoporosis and aortic dissection.RESULTS Serum FSH returned to normal follicular phase levels only on the EE2 regimen. The hypotrophic endometria normalized with either of the two oestrogen regimens with no excessive hypertrophy. Hyperinsulinaemia was suppressed to normal by both EE2 and CE. PTH and 1,25‐dihydroxyvitamin D levels increased on HRT (EE2 > CE), and phosphorus decreased. Alkaline phosphatase, osteocalcin and urinary deoxypyridinoline cross‐links (DPD) were high off therapy; the former two suppressed to high–normal levels on the EE2 regimen, but not on CE, and DPD did not normalize with either HRT. Lipid profiles in these young TS patients were normal. Liver enzymes were mildly elevated off therapy and suppressed to normal levels on both regimens, but more so with EE2.CONCLUSIONS The risk factors embodied in hyperinsulinaemia and enhanced bone turnover which, ultimately, have consequences for TS morbidity, are minimized by HRT. In the short term, neither regimen is effective for bone turnover in adult women with Turner syndrome.
Mdm2 and the p53 pathway in human pituitary adenomas
Authors: Suliman Mohamed , Royds Janice , Cullen Derek , Timperley Walter , Powell Tom , Battersby Robert , Jones T. Hugh 
Published: March 2003

Studies on pituitary tumours have failed to identify mutations in the tumour suppressor gene p53 suggesting that the protein identified is wild type. p21WAF−1 is a downstream effector of p53 which promotes growth arrest. Mdm2 (mouse double minute) is a protein induced by wild type p53 and forms an autoregulatory feedback loop suppressing wild type p53 activity. The purpose of this study was to examine a group of pituitary tumours for expression of p53 and its two downstream effector proteins p21WAF−1 and mdm2 and to compare this with their radiological invasive status and proliferative potential as assessed by Ki‐67 expression.Sixty‐nine tumours removed at transsphenoidal surgery were examined by immunocytochemistry using antibodies against p53, p21WAF−1, mdm2 and Ki‐67 (MIB‐1). The invasive status of the tumours was determined from the preoperative CT/MRI scans. p53 was expressed in 42 of 69 (61%) pituitary adenomas but there was no relationship with either pituitary tumour invasive status (P = 0·71) or volume (P = 0·33). p53 expression correlated, however, with the proliferative state of the tumours as assessed by the MIB‐1 labelling index (P = 0·0065). Invasive tumours had a higher growth fraction than non‐invasive ones (P = 0·027). p21WAF−1 was expressed in the nuclei of 58/69 (84%) pituitary adenomas and its expression correlated with that of p53 (r = 0·26, P = 0·03). Mdm2 was expressed in the cytoplasm of 46/69 (67%) tumours and this correlated with the nuclear staining for p53 (P = 0·022) while nuclear staining was seen in 32/69 (46%) tumours but this did not correlate significantly with nuclear p53 staining (P = 0·096).These results suggest that p53, p21WAF−1 and mdm2 are all expressed in pituitary tumours suggesting that the p53 protein detected by immunocytochemistry is wild type. Expression of p53 is associated with tumours which have a higher proliferative status. The p53 activity is probably the result of upstream signals of local stresses mediated through either genetic change, cytokines, hypoxia or hormonal factors. Our results suggest, however, that the downstream pathway mediated through the activities of p21WAF−1 and mdm2 may be dysfunctional in these tumours.
Effect of exogenous melatonin on vascular reactivity and nitric oxide in postmenopausal women: role of hormone replacement therapy
Authors: Cagnacci Angelo , Arangino Serenella , Angiolucci Marco , Melis Gian Benedetto , Facchinetti Fabio , Malmusi Stefania , Volpe Annibale 
Published: March 2003

OBJECTIVESeveral effects of melatonin are modulated by gonadal steroids and are reduced in ageing women. Administration of melatonin reduces internal carotid artery pulsatility index (PI), and blood pressure in young individuals. Whether these effects are conserved in postmenopausal women and are influenced by hormone replacement therapy (HRT), was herein investigated.DESIGNRandomised, double‐blind placebo controlled study.PATIENTSTwenty‐three postmenopausal women of which 11 were unreplaced with HRT and 12 on the oestrogenic phase of continuous transdermal estradiol (50 µg/day) plus cyclic medroxyprogesterone acetate (5 mg/day × 12 days every 28 days).MEASUREMENTSInternal carotid PI, by colour Doppler, and supine blood pressure were evaluated 90, 180 and 240 minutes following the oral administration of melatonin (1 mg) or placebo. Levels of nitrites/nitrates (NOx), the stable derivatives of nitric oxide, were also evaluated in samples collected 90 minutes following the administration of placebo or melatonin.RESULTSIn women not on replacement therapy melatonin was ineffective. In HRT‐treated women, melatonin reduced internal carotid artery PI (P = 0·005). The effect was maximal within 90 minutes, and maintained for at least 240 minutes, with melatonin levels in the nocturnal physiological range. Systolic and diastolic blood pressures were reduced of 8 mmHg (P = 0·038) and 4 mmHg (P = 0·045), respectively, while NOx levels were significantly increased (P = 0·024).CONCLUSIONSThe circulatory response to melatonin is conserved in postmenopausal women with but not without hormone replacement therapy. Maintenance of the cardiovascular response to melatonin, may be implicated in the reduced cardiovascular risk of postmenopausal women with hormone replacement therapy.
Central precocious puberty: clinical and laboratory features*
Authors: Chemaitilly Wassim , Trivin Christine , Adan Luis , Gall Valérie , Sainte‐Rose Christian , Brauner Raja 
Published: March 2003

To determine whether the initial presentation of patients with central precocious puberty (CPP) varies according to the aetiology, whether this permits the differentiation between idiopathic and organic forms, and whether the body mass index (BMI) and plasma leptin concentrations are linked to gonadotrophin secretion.The clinical and laboratory features of 256 patients (26 boys and 230 girls) with CPP were studied separately in boys and girls. We compared patients with idiopathic CPP (seven boys and 186 girls) to those with organic CPP, whose pubertal development revealed a central nervous system (CNS) lesion (five boys and 11 girls), and to patients with organic CPP associated with a previously treated CNS lesion (14 boys and 33 girls).Boys with organic CPP, having revealed or treated CNS lesions, started their puberty earlier (3·0 ± 1·0 years and 6·7 ± 0·5 years) than boys with idiopathic CPP (8·5 ± 0·2 years, P < 0·01 and < 0·05). Boys with organic CPP associated with a treated CNS lesion had lower luteinizing hormone (LH)/follicle stimulating hormone (FSH) peaks ratio after stimulation with gonadotrophin releasing hormone (GnRH) (1·6 ± 0·5) than did boys with idiopathic CPP (2·2 ± 0·3, P < 0·05). Girls with organic CPP revealing a CNS lesion started their puberty earlier (3·6 ± 0·9 years) than girls with idiopathic CPP (6·6 ± 0·1 years, P < 0·0 l) and had higher LH (P < 0·01) and FSH peaks (< 0·05). Girls with organic CPP associated with a treated CNS lesion had higher BMI (1·8 ± 0·2 z‐score) than did girls with idiopathic CPP (1·3 ± 0·1 zs, P < 0·05), higher leptin concentrations (11·7 ± 1·8 µg/l vs. 7·7 ± 0·5 µg/l, P < 0·0 l), LH peak (P < 0·01), FSH peak (P < 0·05) and LH/FSH peaks ratio (1 ± 0·1 vs. 0·8 ± 0·1, P < 0·05). Only 12·4% of the girls with idiopathic CPP had BMI‐zs < 0, and their plasma leptins were positively correlated with BMI (P < 0·0001).The features of central precocious puberty vary according to the aetiology, but it is impossible to exclude a central nervous system lesion in a given patient with central precocious puberty without performing central nervous system imaging. This imaging remains necessary in all cases of central precocious puberty. Most of the girls with idiopathic central precocious puberty had increased BMI, but we found no correlation between plasma leptin concentrations and gonadotrophin secretion.