bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interleukin‐2 given to asymptomatic HIV‐infected individuals leads to an exaggerated response of the pituitary gland to the action of CRH
Authors: Witzke Oliver , Winterhagen Toni , Kribben Andreas , Philipp Thomas , Mann Klaus , Reinhardt Walter 
Published: June 2003

Summarybackground and aims Studies investigating the impact of interleukin‐2 (IL‐2) on the corticotroph axis have shown that IL‐2 can stimulate cortisol and ACTH secretion. However, the site, the time course and the mechanisms of IL‐2 stimulation of the corticotroph axis are still not known. The aim of this study was to gain insight into the mechanisms of IL‐2 stimulation of the corticotroph axis.patients and methods A total of 9 × 106 IU/day IL‐2 were given to 18 male HIV‐infected patients treated with a combination of HIV antiviral drugs (usually two reverse‐transcriptase inhibitors and one protease‐inhibitor) over a course of 4–5 days. Seven of these 18 patients received a second course of IL‐2.results Cortisol levels increased significantly (P < 0·001) from baseline levels (427 ± 118 nmol/l) to 746 ± 132 nmol/l after 4 days of IL‐2 therapy with a gradual decrease to baseline within 10 days after the end of therapy. ACTH showed a similar pattern rising from 5·9 ± 1·9 pmol/l at baseline to 12·4 ± 4·6 pmol/l on day 4 (P < 0·001). The cortisol response after CRH application (carried out at 15·00 h) was significantly more pronounced at the end of IL‐2 application (CRH test B, baseline: 330 ± 59 nmol/l, peak 774 ± 134 nmol/l, 135% increase) when compared to pretreatment (CRH test A, baseline: 226 ± 73 nmol/l, peak 459 ± 103 nmol/l, 103% increase, P ≤ 0·0001). The cortisol response 9 days after the end of IL‐2 administration showed a similar pattern when compared to pretreatment values. The ACTH response after CRH was essentially paralleled by the cortisol response (CRH test B, baseline: 6·1 ± 2·8 pmol/l, peak 16·0 ± 4·4 pmol/l, 170% increase; CRH test A, baseline: 4·3 ± 1·9 pmol/l, peak 9·2 ± 3·1 pmol/l, 110% increase, P = 0·0005). Furthermore, we observed higher ACTH and cortisol concentrations in the morning when compared to late afternoon values during treatment with IL‐2 [cortisol: baseline: 426 ± 73 nmol/l (8·00 h); 226 ± 73 nmol/l (15·00 h)]; day 4: [746 ± 132 nmol/l (8·00 h); 339 ± 59 nmol/l (15·00 h)]; ACTH: baseline: [5·9 ± 1·9 pmol/l (8·00 h); 4·3 ± 1·9 pmol/l (15·00 h)]; day 4: [12·4 ± 4·7 pmol/l (8·00 h); 6·1 ± 2·8 pmol/l (15·00 h)].conclusion The data from this in vivo study suggest that IL‐2 most likely resulted in corticotroph hyperplasia leading to an exaggerated response of the pituitary gland to the action of CRH.
Growth without growth hormone: growth pattern and final height of five patients with idiopathic combined pituitary hormone deficiency
Authors: Lazar Liora , Dan Sivan , Phillip Moshe 
Published: June 2003

Summarybackground Growth without GH has been reported in patients with organic combined pituitary hormone deficiency (CPHD) after resection of craniopharyngiomas and hypothalamic tumours or in septo‐optic dysplasia.methods This study describes the growth pattern and final height of five children (four boys, one girl) with idiopathic CPHD (GH, TSH, ACTH, LH and FSH) who maintained normal growth despite persistent GH deficiency throughout the growth period.results Presenting findings were borderline small penis in two children diagnosed at ages 3 and 9 years, and absence of pubertal signs in three adolescents diagnosed at age 12·8–13·7 years. The latter three patients also exhibited acromegaloid features. The height of all patients was within the 10–25th percentiles, and weight at the 25–50th percentiles. Although they were moderately overweight, accelerated weight gain was not observed. Prepubertal growth rate was 4–5 cm/year. The pubertal growth period, starting after initiation of sex hormone therapy (chronological age 15·9–16·3 years and bone age 12·5–14·5 years) continued for 4–5·5 years. Total pubertal growth was 6–11·7 cm with reduced growth spurt. Final height, which was attained at an advanced age (19–22 years), was 170–179 cm in the boys and 164 cm in the girl, equal to or exceeding the target height range. Repeated hormonal evaluations revealed undetectable GH and IGF‐I levels, and no evidence of hyperprolactinaemia or hyperinsulinism.conclusions Final height attainment within or above target height range may occur in patients with idiopathic CPHD despite persistent GHD. As this was not mediated by GH, IGF‐I, insulin or prolactin, some other growth factors probably played a growth‐promoting role.
Increased fracture rates in Turner's syndrome: a nationwide questionnaire survey
Authors: Gravholt Claus Højbjerg , Vestergaard Peter , Hermann Anne Pernille , Mosekilde Leif , Brixen Kim , Christiansen Jens Sandahl 
Published: June 2003

Summarybackground and objectives Reduced bone mineral content (BMC) and bone mineral density (BMD) have previously been reported in Turner's syndrome, although appropriate GH treatment and early induction of puberty seem to permit normal bone mass accumulation. Furthermore, an increased risk of fractures and osteoporosis have been reported in a registry study. The aim of the present study was to further characterize the risk of fractures in TS and to explore risk factors, in a historical follow‐up survey based on a self‐administered questionnaire.study groups The questionnaire was issued to all females with TS (n = 632) in Denmark and to 1888 randomly selected controls (C) matched for age and geographical region. A total of 322 patients (51%) and 1169 controls (62%) returned the questionnaire.results TS women were younger than C (30 years, range: 1–73 years vs. 34 years, range 2–82 years, P < 0·0005), smoked less often (17%vs. 27%, P < 0·0005), and had less frequent spontaneous menstruation (18%vs. 86%, P < 0·0005). In contrast, they used hormonal replacement therapy (HRT) more often (71%vs. 7%, P < 0·0005). The median age at start of HRT was 16 years (range 8–59 years) in TS vs. 42 years (range 12–53 years) in C (P < 0·0005). Above the age of 15 years, 83% of TS and 8% of C used HRT. GH had been used by 37% of TS but only 0·2% of C. Both type 1 and 2 diabetes were increased sevenfold among TS. Altogether, 77 individuals with TS had 109 fractures. The fracture risk was increased in TS [hazard ratio (HR, status) 1·35, confidence interval (CI) 1·04–1·75, P = 0·025]. Time to first fracture was reduced in TS (53 ± 2 vs. 63 ± 1; log‐rank P = 0·03). Spontaneous menstruation was protective in females above 13 years of age (HR: 0·70, CI 0·54–0·93, P = 0·012). A history of parental fractures increased the risk (HR 1·92, CI 1·62–2·27, P < 0·001). Fractures of the forearm was more frequent among TS (P = 0·02).conclusion The present nationwide survey, based on questionnaires, confirms an increased risk of early fractures in TS, especially in those without ovarian function and with a positive family history of fracture and osteoporosis. It thereby emphasizes the need for being vigilant with respect to BMD measurements in these patients.
Relationship between leptin levels and bone mineral density in the elderly
Authors: Zoico Elena , Zamboni Mauro , Adami Silvano , Vettor Roberto , Mazzali Gloria , Tosoni Paolo , Bissoli Luisa , Bosello Ottavio 
Published: June 2003

Summaryobjective To assess the relationship between circulating leptin levels, bone mineral content and density in the elderly.design A cross‐sectional study.patients A cohort of 92 men and 171 women, with ages ranging from 68 to 75 years, selected as a healthy and normal functioning group, in the city centre of Verona.measurements Plasma leptin levels were determined in each participant. Body composition was evaluated with dual energy X‐ray absorptiometry (DXA). Bone mineral content (BMC) and bone mineral density (BMD) were measured at whole‐body, hip and femoral neck level in all subjects.results In both men and women a significant relationship between fat mass and whole‐body BMC or BMD was found. The strength of this association was consistently reduced after adjustment for plasma leptin. A significant association between circulating leptin levels, whole‐body, total hip and femoral neck BMC and BMD was found in both sexes. This association retained the statistical significance after adjustment for fat mass percentage, especially in women. In stepwise multiple linear regression analyses, leptin was shown to be a significant predictor of whole‐body, total hip and femoral neck BMC and BMD, independently of age and the percentage of body fat in both sexes. The circulating levels of leptin accounted for a variance in whole‐body BMC of 8·9% in men and 18·2% in women, and in whole‐body BMD of 10·6% in women.conclusion Our data show a significant relationship between leptin, bone mineral mass and density in healthy elderly men and women.
Left ventricular mass index and ventricular septum thickness are associated with serum dehydroepiandrosterone‐sulphate levels in hypertensive women
Authors: Szathmári Miklós , Treszl András , Vásárhelyi Barna 
Published: June 2003

Summaryobjective  Several data indicate that endogenous sex steroids might influence left ventricular mass. Our aim was to examine the association between dehyroepiandrosterone‐sulphate (DHEAS) levels and left ventricular mass index (LVMI) and ventricular septal thickness (VST) in pre‐ and in postmenopausal women with treated essential hypertension.patients and methods  LVMI and VST were related to serum DHEAS in 26 pre‐ and in 34 postmenopausal women. The associations between DHEAS and LVMI, VST were adjusted for body mass index, duration of hypertension, systolic blood pressure, serum cholesterol and testosterone levels using a multiple regression model.results  In premenopausal women there was a significant linear correlation between DHEAS and LVMI (P < 0·02) after adjustment for confounding variables. In contrast, DHEAS was inversely correlated with LVMI and VST in postmenopausal women (r = −0·49, P < 0·02, r =−0·42, P < 0·02, respectively). These associations also remained significant (P = 0·04, P = 0·03, respectively) after adjustment for confounding variables.conclusion  DHEAS might be an independent determinant of LVMI and VST. Its effect on the heart may depend on hormonal milieu. In premenopausal women, DHEAS might have androgenic effects and might enhance fibroblast proliferation; while during the postmenopausal period it is dominantly oestrogenic in action, with antiproliferative effect on cardiac cells.
Characterization of the intracellular mechanisms mediating somatostatin and lanreotide inhibition of DNA synthesis and growth hormone release from dispersed human GH‐secreting pituitary adenoma cells in vitro
Authors: Florio Tullio , Thellung Stefano , Corsaro Alessandro , Bocca Liliana , Arena Sara , Pattarozzi Alessandra , Villa Valentina , Massa Alessandro , Diana Fabrizio , Schettini Daria , Barbieri Federica , Ravetti Jean Louis , Spaziante Renato , Giusti Massimo , Schettini Gennaro 
Published: June 2003

Summaryobjective Somatostatin is an endogenous inhibitor of hormone secretion and cell proliferation. Treatment with somatostatin analogues in humans causes a reduction in size and secretory activity of endocrine tumours, including GH‐secreting pituitary adenomas. This study was aimed to characterize the intracellular mechanisms mediating the in vitro antiproliferative and antisecretory effects of somatostatin and its analogue lanreotide, on primary cultures of GH‐secreting pituitary adenoma cells.design Thirteen GH‐secreting pituitary adenoma postsurgical specimens were analysed for somatostatin receptor (SSTR) mRNA expression and a subset of them was analysed in vitro for the effect of somatostatin on cell proliferation, assessed by means of [3H]‐thymidine uptake, and GH release, using an immunoradiometric assay. Moreover, the intracellular signalling involved in such effects has been studied.results All the adenomas analysed expressed at least one somatostatin receptor subtype mRNA. SSTR2 mRNA was identified in 77% of the adenomas, SSTR1 and SSTR3 in 69% and SSTR5 in 60%. Somatostatin and lanreotide inhibited cell proliferation in phorbol ester (PMA)‐stimulated conditions (10/13 adenomas), as well as after fetal calf serum (3/3 adenomas) or IGF‐I stimulation (2/2 adenomas). Conversely, GHRH or forskolin treatments did not significantly affect DNA synthesis in adenoma cells in the presence or absence of somatostatin (2/2 and 4/4 adenomas, respectively). Vanadate pretreatment reversed somatostatin inhibition of PMA‐induced DNA synthesis suggesting an involvement of tyrosine phosphatase in this effect (2/2 adenomas); this was confirmed by the direct induction of tyrosine phosphatase activity in two adenomas after somatostatin treatment. Somatostatin and also lanreotide caused significant inhibition of phorbol ester, forskolin, GHRH and KCl‐dependent increase of GH secretion in the culture medium. Moreover, voltage‐sensitive calcium channel activity induced by 40 mm KCl depolarization in microfluorimetric analysis, was significantly reduced (5/5 adenomas).conclusions These data show that somatostatin and lanreotide inhibit human GH‐secreting pituitary adenoma cell proliferation and hormone release in vitro, and suggest that the activation of tyrosine phosphatases may represent intracellular signals mediating the antiproliferative effects and that the inhibition of the voltage‐dependent calcium channels and adenylyl cyclase activities may control GH secretion.
Multiple endocrine neoplasia type 1 (MEN1): genetic and clinical analysis in the Southern Chinese
Authors: Tso A. W. K. , Rong R. , Lo C. Y. , Tan K. C. B. , Tiu S. C. , Wat N. M. S. , Xu J. Y. , Villablanca A. , Larsson C. , Teh B. T. , Lam K. S. L. 
Published: June 2003

Summaryobjective Multiple endocrine neoplasia type 1 (MEN1) is characterized by a triad of neoplasia affecting the parathyroid glands, enteropancreatic endocrine tissue and the anterior pituitary gland.design In order to define the prevalence of MEN1 germ‐line mutations in Southern Chinese patients with MEN1 syndrome, we performed direct sequencing of the entire open reading frame of the MEN1 gene for 12 index patients and their first‐degree relatives.results Six patients had familial MEN1 syndrome and six had apparently sporadic disease. Nine different germ‐line mutations at the MEN1 gene were identified, including three novel mutations [248–249delTT in exon 2, K559X(AAG → TAG) in exon 10 and IVS 2nt + 2(G → T) in intron 2]. All patients with familial MEN1 syndrome were heterozygous carriers of a germ‐line mutation and MEN1‐related disorders were only evident in their first‐degree relatives who also carried the mutation. All patients with an enteropancreatic lesion were mutation carriers and the absence of mutation in three apparently sporadic MEN1 patients with only hyperparathyroidism and pituitary microadenoma might represent the presence of MEN1 phenocopy.conclusions The finding of MEN1 germ‐line mutation in all patients with familial MEN1 syndrome suggests that genetic screening should be useful in our population to identify affected individuals within a kindred and allow early detection of MEN1‐related tumours.
The effect of cryptorchidism on inhibin B in a subfertile population
Authors: De Gouveia Brazao C. A. , Pierik F. H. , Erenpreiss Y. , De Jong F. H. , Dohle G. R. , Weber R. F. A. 
Published: June 2003

objective Prepubertal cryptorchidism may cause fertility problems in adulthood, due to impaired spermatogenesis. Serum inhibin B has emerged as an accurate marker of spermatogenesis. The aim of this study was to evaluate the impact of a history of cryptorchidism on serum inhibin B levels and other markers of spermatogenesis in subfertile men.patients and measurements  In a retrospective study, the effect of cryptorchidism on inhibin B, FSH, LH, free testosterone, testicular volume and semen parameters was assessed in a case–control study within a population of 2613 subfertile men. Of these, 161 and 102 subjects had a history of, respectively, unilateral and bilateral cryptorchidism that was treated by orchiopexy in childhood. Hormone data were complete for 64 cryptorchid patients (32 unilateral and 32 bilateral). A group of 128 patients was randomly selected out of the remaining group of 2350 men with idiopathic subfertility. An additional control group consisted of 32 fertile men from the general population.results In cryptorchid subfertile men, inhibin B concentrations were significantly lower than in noncryptorchid subfertile men and fertile men (103 ng/l, 143 ng/l and 148 ng/l, respectively; P < 0·01). The FSH concentration was significantly higher in cryptorchid men vs. noncryptorchid men and controls (6·1 IU/l vs. 3·3 and 2·9 IU/l, respectively; P < 0·01).Testicular volumes and sperm concentration of cryptorchid men were significantly lower than in noncryptorchid subfertile men (12 vs. 15 ml, P < 0·01 and 3·8 × 106 sperm/ml vs. 17·4 × 106 sperm/ml; P < 0·05). A significantly higher inhibin B level and sperm concentration was observed in men undergoing orchiopexy at an early age (1–4 years) compared with men treated between 5 and 9 years or later (P < 0·05).conclusion Spermatogenesis is more impaired in cryptorchid subfertile men compared to men with idiopathic subfertility, as reflected by a lower inhibin B concentration.
Role of protein binding in renal elimination of leptin
Authors: Landt Michael , Ludbrook Philip A. , Billadello Joseph J. 
Published: June 2003

Summaryobjective Leptin, a hormone produced by fat which signals to the brain the extent of fat stores, is known to be eliminated from circulation primarily by the kidney. The hormone circulates in both free and protein‐bound forms, but there is little information concerning the inter‐relationship of these forms of leptin, or which form is influenced by physiological processes such as renal elimination. We studied total, free and bound concentrations of leptin in ambulatory adults undergoing catheterization for diagnosis/management of congenital cardiac disease.design Blood specimens were collected from both the arterial circulation and the renal vein, for determination of the fractional extraction of leptin resulting from a single pass through the kidney.patients Thirteen subjects were studied.measurements Total leptin concentrations were measured by radioimmunoassay, and free/protein‐bound leptin concentrations were quantified by an high‐performance liquid chromatography method. Adequacy of renal vein sampling was assessed by comparing the creatinine concentration of arterial and venous specimens.results Mean fractional extraction of creatinine was 28 ± 7% in the 13 subjects studied. Fractional extraction of total leptin was 18 ± 8%, significantly less than that for creatinine. Fractional extraction of total leptin was not related to arterial leptin concentration or the fractional extraction of creatinine. Both free and bound fractions of leptin were significantly reduced by passage through the kidney, with fractional extractions of 22% and 25%, respectively. Efficiency of extraction was not influenced by the relative proportion of free or bound leptin fractions. Leptin‐binding capacity (a measure of the concentrations of leptin‐binding proteins) was not altered by passage through the kidney.conclusions Both free and bound leptin are metabolically active with regard to elimination. Protein‐bound leptin equilibrates with the free leptin fraction in circulation as the result of a dynamic equilibrium. The data are consistent with either glomerular filtration or active uptake as mechanisms of elimination. Leptin‐binding proteins are apparently neither eliminated or produced by the kidney.
Drought and aquatic community resilience: the role of eggs and seeds in sediments of temporary wetlands
Authors: Brock M. A. , Nielsen Daryl L. , Shiel Russell J. , Green John D. , Langley John D. 
Published: June 2003

Summary1. A long‐lived bank of propagules consisting of eggs, seeds and spores is one mechanism that allows aquatic communities to survive drought. A drying (drought) event is, for aquatic organisms in a temporary wetland, a phase from which communities must recover. Such a dry phase is often considered a disturbance but should not be considered adverse or catastrophic for the organisms that have evolved to live in temporarily wet habitats.2. This paper explores the parallels between the egg bank of zooplankton and the seed bank of aquatic plants as means of survival in temporary wetlands. The resilience of communities in temporary wetland ecosystems is assessed by examining dormancy, hatching, germination, establishment and reproduction of animals and plants from the egg and seed banks of wetlands with a range of wetting and drying regimes.3. Both the zooplankton and aquatic plants of the temporary wetlands studied rely on their egg and seed banks as a means for surviving drying. These communities recover after the disturbance of drying by means of specific patterns of dormancy, dormancy breakage, hatching, germination, establishment and reproduction. Spatial and temporal patterns of species richness allow resilience through dormancy, as not all species are present at all sites and not all species hatch and germinate at the same time. Multiple generations in the egg and seed bank and complexity of environmental cues for dormancy breakage also contribute to the ecosystem's ability to recover after a drying event. A persistent egg and seed bank allows species‐rich communities to hatch, germinate and develop rapidly once dormancy is broken. Rapid establishment of species‐rich communities that reproduce rapidly and leave many propagules in the egg and seed bank also facilitates community recovery on flooding of a temporary wetland after a drying event.4. To maintain the diversity of temporary wetland communities through droughts and floods we need to manage the dry and wet phases of wetlands. To conserve a wide range of wetland types, we need to maintain a variety of hydrological patterns across the landscape.