bluuebunny/crossref_metadata_2025_split huggingface dataset:
An ultrasensitive assay revealed age‐related changes in serum oestradiol at low concentrations in both sexes from infancy to puberty
Authors: Ikegami Saiko , Moriwake Tadashi , Tanaka Hiroyuki , Inoue Masaru , Kubo Toshihide , Suzuki Satoshi , Kanzaki Susumu , Seino Yoshiki 
Published: March 2003

OBJECTIVE Intensive studies of oestrogen receptors have suggested extragonadal functions of oestrogen. However, the in vivo extragonadal functions of oestradiol remain unclear because of the lack of an adequate assay system at low concentrations. In this study, we assessed the usefulness of a new ultrasensitive assay for children.METHODS Serum oestradiol was measured with an ultrasensitive assay (assayable concentration: 5– 1835 pmol/l: ESTR‐US‐CT, CIS biointernational, France). Intra‐ and interassay coefficients of variation at low concentrations (< 36·7 pmol/l) were 8·2 ± 6·8 (0·1–31·2)% and 8·3 ± 3·7 (7·5–12·9)%, respectively.SUBJECTS Sera from 88 healthy children (55 males and 33 females; 1 month to 16 years old) and 31 patients who underwent gonadal suppression therapy were analysed.RESULTS Age‐related changes were observed in both sexes. Serum oestradiol concentrations in childhood decreased slightly compared to those in infancy, then increased at puberty. Most prepubertal children showed oestradiol concentrations lower than 36·7 pmol/l. A study on patients who underwent gonadal suppression therapy revealed oestradiol changes within low concentrations, depending on the stage of the therapy.CONCLUSIONS The new assay was considered precise enough for the assessment of oestradiol secretion at low concentrations in childhood. Age‐related changes in serum oestradiol suggested gonadal activity in the prepubertal period. This assay could be a powerful tool for investigating novel oestradiol functions in vivo.
Factors predicting adult height in girls with idiopathic central precocious puberty: implications for treatment*
Authors: Adan Luis , Chemaitilly Wassim , Trivin Christine , Brauner Raja 
Published: March 2003

Summaryobjectives To optimize the indications for treating girls with idiopathic central precocious puberty with GnRH analogues, since outcomes may vary.design Comparison of adult heights with the data at initial evaluation and the target heights.patients Group 1 patients (n = 43) were treated with GnRH analogue from 7·9 ± 0·2 years to 10·8 ± 0·1 years (bone age: 10·3 ± 0·2 years to 12·2 ± 0·1 years) and group 2 patients (n = 29) were monitored without treatment because their predicted adult heights were > 155 cm. The criteria for treatment were a predicted height < 155 cm and/or a LH/FSH peaks ratio of > 0·6.results At initial evaluation, group 1 patients had greater breast development (P = 0·001) and bone age advances (2·0 ± 0·2 years) than those of group 2 (1·3 ± 0·2 years, P < 0·03), and higher plasma oestradiol concentrations (139 ± 11 pmol/l vs. 62 ± 7 pmol/l, P = 0·0001), LH peak (12·2 ± 1·8 IU/l vs. 5·8 ± 2·2 IU/l, P = 0·0001) and LH/FSH peaks ratio (1·3 ± 0·2 vs. 0·5 ± 0·1, P = 0·0001). The predicted height for group 1 at the onset of treatment (156 ± 1·2 cm) was lower than the adult height (159·5 ± 0·8 cm, P = 0·002), but the two were similar (164·1 ± 1·2 cm vs. 162·7 ± 0·9 cm) for group 2. In group 1, the difference between these heights (mean 3·4 cm) was positively correlated with the bone age advance (r = 0·51, P = 0·001), but not with chronological or bone ages, oestradiol, LH peak, LH/FSH peaks ratio before treatment or its duration. It was 5·3 ± 1·2 cm in the 28 patients with a bone age advance of > 2 years and 0 ± 1·3 cm in the other 15 (P < 0·02). It was 6·1 ± 1·3 cm in the 24 patients with predicted height < 155 cm, and –0·1 ± 1·1 cm in the other 18 (P = 0·002). The 72 patients included nine who attained an adult height over 5 cm shorter than the target height (seven treated and two untreated). The seven treated subjects included two who had retarded intrauterine growth.conclusions Treatment of girls with idiopathic central precocious puberty with GnRH analogues produced a mean height increase of 3·4 cm between the predicted and adult heights. The increase was greater for girls with a bone age advance of > 2 years and a predicted height < 155 cm. Adult height is spontaneously preserved in the slowly progressing form. The classical and slowly progressing forms can be distinguished by the degrees of breast development and bone age advance.
Acromegaly: evidence for a direct relation between disease activity and cardiac dysfunction in patients without ventricular hypertrophy
Authors: Herrmann B. L. , Bruch C. , Saller B. , Bartel T. , Ferdin S. , Erbel R. , Mann K. 
Published: March 2003

Summarybackground and aims Cardiac abnormalities, such as cardiomegaly and congestive heart failure, occur frequently in advanced acromegaly. Abnormalities of systolic and diastolic function, mostly associated with left ventricular (LV) hypertrophy, have been reported. The impact of disease activity on LV performance in patients with normal or slightly elevated LV muscle mass has not been demonstrated.patients and methods Conventional two‐dimensional/Doppler echocardiography and tissue Doppler imaging (TDI) of the mitral annulus were performed in 13 patients with active acromegaly (AA) and normal or slightly elevated LV muscle mass (< 140 g/m2) and in 19 cured/well‐controlled patients (CA). A group of 21 volunteers without symptoms or signs of cardiac disease served as controls (CON). The combined myocardial performance index (Tei‐Index) was determined in all patients and controls.results Muscle mass index of the left ventricle, ejection fraction, fractional shorting, E/ET‐ratio, systolic (ST) and late diastolic (AT) annular velocities did not differ significantly between the three groups. In the AA group, the early diastolic annular velocity ET[7·13 ± 2·11 (AA); 9·83 ± 3·29 (CA); 10·10 ± 1·70 m/s (CON); P < 0·05 AA vs. CA, P < 0·005 AA vs. CON] and the ET/AT‐ratio [0·71 ± 0·26 (AA); 0·95 ± 0·33 (CA); 1·00 ± 0·15 m/s (CON); P < 0·05 AA vs. CA, P < 0·005 AA vs. CON] were significantly reduced. Patients with AA had a longer deceleration time [209 ± 19 (AA); 179 ± 22 (CA); 185 ± 26 ms (CON); P < 0·05]. The Tei‐Index was significantly higher in AA in comparison with CON [0·50 ± 0·15 (AA); 0·48 ± 0·12 (CA); 0·41 ± 0·10 (CON); P < 0·05 AA vs. CON]. Subjects with CA did not differ significantly from controls with respect to 2‐D/Doppler echo‐ and TDI‐derived parameters.conclusion The data demonstrate that diastolic dysfunction can be verified by tissue Doppler imaging in patients with active acromegaly with normal or slightly elevated muscle mass of the left ventricle and seems to be related to disease activity. The Tei‐Index as a sensitive combined myocardial performance index can be used to complete the assessment of systolic and diastolic LV performance in acromegalic patients.
The GH‐releasing effect of ghrelin, a natural GH secretagogue, is only blunted by the infusion of exogenous somatostatin in humans
Authors: Di Vito Lidia , Broglio Fabio , Benso Andrea , Gottero Cristina , Prodam Flavia , Papotti Mauro , Muccioli Giampiero , Dieguez Carlos , Casanueva Felipe F. , Deghenghi Romano , Ghigo Ezio , Arvat Emanuela 
Published: March 2003

Summaryobjective Ghrelin, a 28‐amino‐acid peptide purified from the stomach and showing a unique structure with an n‐octanoyl ester at the serine 3 residue, is a natural ligand of the GH secretagogue (GHS) receptor (GHS‐R). Ghrelin strongly stimulates GH secretion in both animals and humans, showing a synergistic effect with GH‐releasing hormone (GHRH) but no interaction with synthetic GHS. However, the activity of ghrelin as well as that of non‐natural GHS is not fully specific for GH; ghrelin also induces a stimulatory effect on lactotroph and corticotroph secretion, at least in humans.design To further clarify the mechanisms underlying the GH‐releasing activity of this natural GHS, we studied the effects of somatostatin (SS, 2·0 µg/kg/h from −30 to +90 min) on the endocrine responses to ghrelin (1·0 µg/kg i.v. at 0 min) in seven normal young male volunteers [age (mean ± SEM) 28·6 ± 2·9 years; body mass index (BMI) 22·1 ± 0·8 kg/m2] . In the same subjects, the effect of SS on the GH response to GHRH (1·0 µg/kg i.v. at 0 min) was also studied.measurements Blood samples were taken every 15 min from −30 up to +120 min. GH levels were assayed at each time point in all sessions; PRL, ACTH and cortisol levels were assayed after ghrelin administration alone and during SS infusion.results The GH response to ghrelin (hAUC0′→120′ 2695·0 ± 492·6 µg min/l) was higher (P < 0·01) than that after GHRH (757·1 ± 44·1 µg min/l). SS infusion almost abolished the GH response to GHRH (177·0 ± 37·7 µg min/l, P < 0·01); the GH response to ghrelin was inhibited by SS (993·8 ± 248·5 µg min/l, P < 0·01) but GH levels remained higher (P < 0·05) than with GHRH. Ghrelin induced significant increases in PRL, ACTH and cortisol levels and these responses were not modified by SS.conclusions Ghrelin, a natural GHS‐R ligand, exerts a strong stimulatory effect on GH secretion in humans and this effect is only blunted by an exogenous somatostatin dose which almost abolishes the GH response to GHRH. The stimulatory effect of ghrelin on lactotroph and corticotroph secretion is refractory to exogenous somatostatin, indicating that these effects occur through pathways independent of somatostatinergic influence.
What is the role of the insulin‐like growth factor system in the pathophysiology of cancer cachexia, and how is it regulated?
Authors: Crown A. L. , Cottle K. , Lightman S. L. , Falk S. , Mohamed‐Ali V. , Armstrong L. , Millar A. B. , Holly J. M. P. 
Published: March 2003

Summaryobjective and background The cancer cachexia syndrome is characterized by anorexia, weight loss with muscle wasting and increased energy expenditure. It is associated with increased morbidity and mortality, but its aetiology is poorly understood and no effective therapeutic intervention is available. It may result from an imbalance between the activity or effect of anabolic and catabolic hormones, mediated by the inflammatory cytokines. IGF‐I is a potent anabolic agent, with therapeutic potential. Our objective was to investigate the role and regulation of the IGF system in cancer cachexia.design and patients We set up a prospective study of 30 patients with newly diagnosed unresectable non‐small cell lung cancer, together with a cross‐sectional comparison group of healthy volunteers.measurements We examined the relationship between aspects of the IGF system, including IGFBP‐3 proteolysis (using Western ligand and immunoblotting and an in vitro IGFBP‐3 protease assay); the inflammatory cytokines and their soluble receptors; and food intake and nutritional status (including biochemical and anthropometric assessments).results Although we did not observe a marked reduction in food intake in the cancer patients, the majority lost weight and functionally important lean body mass. We observed GH resistance in the cancer patients, and intermittent proteolysis of IGFBP‐3, which correlated with the circulating interleukin‐6 (IL‐6) concentration. The pattern of IGFBP‐3 proteolysis was unusual, with a prominent 17‐kDa fragment. Less IGFBP‐3 proteolysis was associated with more weight loss, suggesting that this could be a protective counter‐regulatory mechanism, increasing IGF‐I bioavailability to the tissues.conclusions Cancer cachexia in humans is a complex condition. Patients tend to be GH resistant. The significance of the intermittent increases in IGFBP‐3 proteolysis, which may be regulated by IL‐6, remains uncertain. A better understanding of the pathophysiology should enable the development of novel therapeutic approaches.
Sympathetic nerve hyperactivity is associated with increased peripheral vascular resistance in hypopituitary patients with growth hormone deficiency
Authors: Scott Eleanor M. , Greenwood John P. , Stoker John B. , Mary David A. S. G. , Gilbey Stephen G. 
Published: March 2003

Summaryobjective Hypopituitary patients with untreated GH deficiency have increased cardiovascular mortality. Sustained vasoconstriction is an important factor in the development of hypertension and insulin resistance. This study was designed to see whether peripheral vascular resistance was increased in subjects with GH deficiency and to examine the mechanisms involved.methods Nine patients with GH deficiency and nine matched control subjects were studied. Calf vascular resistance was measured by venous occlusion plethysmography and sympathetic vasoconstrictor nerve activity by peroneal microneurography.results Subjects with GH deficiency had a significantly lower blood flow (by 31%) and higher vascular resistance (by 48%) than the control group. In addition, they had a significantly higher sympathetic vasoconstrictor activity (by 67%) and this correlated with the vascular resistance (r = 0·45; P < 0·04).conclusions Patients with GH deficiency have an increased peripheral vascular resistance that is contributed to by an increase in central sympathetic vasoconstrictor discharge to the peripheral vasculature. This could be important in the development of cardiovascular disease in this condition.
A comparison of the relative efficacy of antiandrogens for the treatment of acne in hyperandrogenic women
Authors: Carmina Enrico , Lobo Rogerio A. 
Published: March 2003

Summaryobjectives To compare the relative effectiveness of two newer antiandrogens (flutamide and finasteride) with cyproterone acetate (CPA), at both low and high doses in the treatment of moderate to severe acne in hyperandrogenic women.subjects and design Forty‐eight hyperandrogenic women were prospectively randomized to the following treatments for 1 year: CPA 2 mg with 35 µg ethinylestradiol; CPA 50 mg with 25 µg ethinylestradiol (reverse sequential regimen); flutamide 250 mg daily; and finasteride 5 mg daily. Assessment of Cook scores was the primary end‐point of the trial. Blood for androgens was obtained at baseline in these women and 30 ovulatory age‐matched controls.results Serum androgens were elevated in all 48 women and was similar in each of the four treatment groups. Cook scores were significantly and equally decreased (59–71%) with flutamide and both low and high doses of CPA (P < 0·01). The decrease with finasteride (−36 ± 2%) was statistically significant but lower than that obtained with the other agents. All treatments were well tolerated.conclusions In hyperandrogenic women with moderate to severe acne, low doses of certain antiandrogens appear to be effective. Low and high doses of CPA with ethinylestradiol were equally effective and were comparable to the effects of a low dose of flutamide. Finasteride was less beneficial.
Relationship between autonomic cardiac activity, b‐cell function, anthropometrics and metabolic indices in type II diabetics
Authors: Manzella Daniela , Carbonella Marco , Ragno Emilia , Passariello Nicola , Grella Rodolfo , Paolisso Giuseppe 
Published: March 2003

Summaryobjective Recent studies have demonstrated that C‐peptide exerts beneficial effects on the diabetic state, including improvements in kidney and nerve function. Thus, we investigated the effect of residual pancreatic C‐peptide secretion on the cardiac autonomic nervous system in well‐ and poorly controlled type II diabetic patients.design Randomised cross‐sectional study.patients Forty type II diabetic patients free from diabetic neuropathy, with similar anthropometric parameters, volunteered for our study.measurements Insulin action, residual pancreatic C‐peptide secretion and the cardiac autonomic nervous system were investigated by euglycaemic hyperinsulinaemic clamp, glucagon bolus test and heart rate variability, respectively. M‐values were used as an index of insulin sensitivity. High frequency (HF) and low frequency (LF) oscillations in heart rate were analysed.results The patients were categorized into those with good (HbA1c ≤ 7·0) and poor (HbA1c ≥ 8·0) metabolic control. The patients with good metabolic control had fasting plasma glucose and C‐peptide levels, plasma area under the curve (auc) insulin and C‐peptide levels, M‐values, LF values and LF/HF ratio significantly lower than patients with poor metabolic control. In contrast, RR interval, total power and HF values had an opposite trend. Basal plasma C‐peptide correlated with LF/HF in patients with good (r = −0·42; P < 0·05) and poor metabolic control (r = −0·45; P < 0·05). An even stronger correlation between auc C‐peptide and LF/HF in patients with good (r = −0·53, P < 0·002) and poor metabolic control (r = −0·49; P < 0·03), as well as in the whole group (r = −0·83; P < 0·001) was found. By multiple regression analyses performed in all patients, LF/HF were independently associated with auc C‐peptide (t = −8·618; P < 0·001) but not basal C‐peptide levels (t = −0·137; P < 0·88).conclusion Our study demonstrated that preserved C‐peptide secretion is associated with a well balanced cardiac autonomic activity in type II diabetic patients.
Bone metabolism and mass in women with Cushing's syndrome and adrenal incidentaloma
Authors: Francucci Cristiano Maria , Pantanetti Paola , Garrapa Gabriella Giuseppina , Massi Fernando , Arnaldi Giorgio , Mantero Franco 
Published: March 2003

Summaryobjective The aim of this study was to compare bone turnover and mass in women with either Cushing's syndrome (CS) or adrenal incidentaloma (AI), which is a possible model for minimal hypersecretion of cortisol.design and patients We studied 15 patients with CS (seven premenopausal and eight postmenopausal women); 23 patients with AI (five premenopausal and 18 postmenopausal women) and 20 matched controls (seven premenopausal and 13 postmenopausal women). Alkaline phosphatase (ALP), bone alkaline phosphatase (bALP), osteocalcin (BGP), 24‐h urinary pyridinoline (Pyr) and deoxypyridinoline (D‐Pyr) and serum and 24‐h urinary calcium and phosphorus were determined in all subjects. Bone mineral density (BMD) at lumbar spine and proximal femur was measured by dual energy X‐ray absorptiometry (DEXA).results We found a significant reduction of BGP and serum phosphorus in CS and AI (P < 0·05) vs. controls and significantly lower levels of Pyr only in CS (P < 0·05) vs. AI and controls. Spinal and femoral BMD z‐values were significantly lower (P < 0·05) in patients with CS (z‐score: lumbar spine −1·44 ± 1·5 and femoral neck −1·07 ± 1; mean ± SD) compared to AI and controls.conclusions Our data show that hypercortisolism reduces osteoblastic function and bone resorption and that osteocalcin can contribute to the precocious diagnosis of silent glucocorticoid excess. Patients with active CS were found to have lower BMD, particularly at vertebral level.
Contrasting effects of intrauterine growth retardation and premature delivery on adult cortisol secretion and metabolism in man
Authors: Walker Brian R. , Irving R. John , Andrew Ruth , Belton Neville R. 
Published: March 2003

Summaryobjective Among babies born at term, intrauterine growth retardation (IUGR) predicts adult hypertension and hyperglycaemia. This might be due to elevated circulating glucocorticoids in adulthood, as described in animal models and in several cohorts of men who were low birthweight at term. Recently, we found that premature low birthweight babies also have adult cardiovascular risk factors, irrespective of IUGR. We have now investigated cortisol secretion in this group.design patients and measurements We studied 29 women and 23 men aged 22–25 years who had been recruited at birth as either normal term (mean birthweight 3·1 kg, gestation 39 weeks), premature appropriate for gestational age (AGA; 1·7 kg, 32 weeks), or premature IUGR (1·7 kg, 35 weeks) babies. Body composition was measured by dual‐energy X‐ray absorptiometry (DEXA); plasma was obtained at 0900 h after overnight fast; and cortisol metabolites were measured in a 24‐h urine sample by gas chromatography/mass spectrometry (GCMS).results Cortisol metabolites were different in men and women, so results were analysed separately. Among women, adult body composition did not differ between groups. Plasma cortisol was not different, but total urinary cortisol metabolite excretion was lower in AGA (3·29 ± 1·91 mg/day, n = 7, P < 0·02) than in either normals (6·77 ± 4·10, n = 14) or IUGR (9·47 ± 8·84, n = 8). Relative excretion of cortisol and cortisone metabolites was not different. Statistically significant differences in cortisol parameters between groups were not seen in men.conclusions Premature AGA baby girls have lower cortisol secretion in adulthood but normal plasma cortisol, suggesting impaired metabolic clearance of cortisol. By contrast, premature IUGR babies maintain normal cortisol secretion as adults, suggesting that IUGR, rather than premature delivery, is responsible for programmed activation of the hypothalamic–pituitary–adrenal (HPA) axis. The ability to detect such dramatic differences in a small study suggests that programming has a potent influence on adult cortisol secretion.
Preliminary evidence that an endogenous retroviral long‐terminal repeat (LTR13) at the HLA‐DQB1 gene locus confers susceptibility to Addison's disease
Authors: Pani Michael A. , Seidl Christian , Bieda Katrin , Seissler Jochen , Krause Maren , Seifried Erhard , Usadel Klaus‐H. , Badenhoop Klaus 
Published: March 2003

SummaryOBJECTIVE Addison's disease is associated with particular haplotypes of the human leucocyte antigen (HLA) region [DQA1*0501‐DQB1*0201 (DQ2) and DQA1*0301‐DQB1*0302 (DQ8)]. This locus harbours several human endogenous retroviral (HERV) long‐terminal repeats (LTR). LTRs within the HLA region have been shown to confer additional susceptibility to type 1 diabetes and rheumatoid arthritis.DESIGN We investigated the role of LTR3 and LTR13, both of which are located adjacent to the DQB1 gene, in Addison's disease.PATIENTS Eighty‐seven patients and 160 controls were genotyped for HLA‐DQA, ‐DQB, and the presence or absence of LTR3 and LTR13.RESULTS Significantly more patients’ HLA alleles than those of controls carried the LTR13 insertion (19·0% vs. 10·6%, P = 0·0143), whereas there was only a trend for LTR3 (allele‐wise chi‐squared test: P = 0·0941). Both, LTR3 and LTR13 are in strong linkage disequilibrium with DQ8, which itself was significantly more frequent in patients than in controls (29·9% vs. 15·0%, P = 0·0089). However, significantly more alleles of DQ8+ patients than of DQ8+ controls carried the LTR13 insertion (44·2% vs. 18·8%, P = 0·0119), whereas we did not observe any difference for LTR3 in the DQ8+ subset (30·5 vs. 23·1%, P = 0·9416).CONCLUSIONS We have found preliminary evidence that the endogenous retroviral element DQ‐LTR13, but not LTR3, is associated with Addison's disease. LTR13 appears to enhance HLA‐DQ8 mediated disease risk. This retroviral insertion therefore might represent a novel susceptibility factor in Addison's disease, but these findings need to be confirmed in a larger data set.