bluuebunny/crossref_metadata_2025_split huggingface dataset:
Plasma adiponectin levels in newborns are higher than those in adults and positively correlated with birth weight
Authors: Kotani Yumiko , Yokota Ichiro , Kitamura Seiko , Matsuda Junko , Naito Etsuo , Kuroda Yasuhiro 
Published: October 2004

objective  The aim of this study was to examine plasma adiponectin concentrations during perinatal the period and their correlations with fetal anthropometric parameters and other hormones.design  Venous cord blood samples were obtained from 59 full‐term healthy newborns (36 males and 23 females, gestational age 37·0–41·4 weeks, birth weight 2,146–4,326 g, birth length 44·0–54·5 cm). The blood samples were also obtained from 15 neonates (postnatal day 3–7) whose cord blood had already been collected and the changes in adiponectin concentrations were examined.measurements  The adiponectin concentration was determined by enzyme‐linked immunosorbent assay. The leptin concentration was determined by radioimmunoassay. Insulin, GH and IGF‐1 concentrations were determined by immunoradiometric assays.results  The plasma adiponectin concentrations in cord blood ranged from 6·0 to 55·8 µg/ml (median 22·4 µg/ml), which were much higher than those in normal‐weight adults (P < 0·0001). In contrast to the findings in adults, these values were positively correlated with birth weight (r = 0·43, P = 0·0005), body mass index (r = 0·44, P = 0·0005), birth weight/birth length ratio (r = 0·46, P = 0·0002) and the leptin concentrations (r = 0·39, P = 0·004). When the effects of fat mass‐related anthropometric parameters such as the birth weight/birth length ratio were controlled, plasma adiponectin concentrations had a significant inverse correlation with insulin concentrations (r = −0·35, P = 0·01). There was no significant gender difference in adiponectin concentrations among newborns. The adiponectin concentrations in neonates (postnatal day 3–7) did not change significantly compared with those in cord blood.conclusions  In contrast to the findings in adults, these results suggest that the adiponectin concentration increases with the mass of fetal fat.
Abnormalities of proinsulin processing in functioning insulinomas: clinical implications
Authors: Wiesli Peter , Perren Aurel , Saremaslani Parvin , Pfammatter Thomas , Spinas Giatgen A. , Schmid Christoph 
Published: October 2004

Summaryobjective  Abnormal proinsulin processing in insulinomas may result in secretory granules containing both insulin and proinsulin, a finding not encountered in healthy β‐cells. The aim of this study was to test whether such abnormalities in the proinsulin to insulin conversion have clinical implications in patients with hypoglycaemic disorders.design  Case‐series.patients and methods  Fifteen patients with histologically confirmed insulinoma and two patients with islet cell hyperplasia were included. The immunohistochemical distribution pattern of proinsulin within the tumour cells was classified as Golgi pattern (predominantly perinuclear immunolabelling) or diffuse pattern (immunolabelling in the periphery of the cells, indicating the presence of proinsulin in secretory granules). Data obtained from the 72‐h fast and arterial calcium stimulation and hepatic venous sampling (ASVS) test were related to the morphological classification.results  Six insulinomas exhibited a diffuse proinsulin distribution pattern, while nine insulinomas and two islet cell hyperplasias disclosed a Golgi pattern. Median proinsulin concentrations at the termination of the fast tended to be higher in patients with the diffuse proinsulin distribution pattern than in patients with the Golgi pattern (86·9 vs. 18·8 pmol/l, P = 0·07). Higher insulin (P < 0·005) and proinsulin (P < 0·05) concentrations were significantly correlated with earlier occurrence of hypoglycaemia during the prolonged fast. During the ASVS test, tumours with the diffuse proinsulin distribution pattern exhibited a higher increase in both insulin (median, 37·3‐ vs. 10·5‐fold, P < 0·05) and proinsulin (6·3‐ vs. 1·6 fold, P < 0·005) concentrations following calcium stimulation than the tumours with the Golgi pattern.conclusions  Abnormalities in the proinsulin to insulin conversion in patients with insulinomas and islet cell hyperplasia correlate with impaired regulation of both insulin and proinsulin secretion during the prolonged fast as well as the ASVS test.
Inhibition of endothelial proliferation by the somatostatin analogue SOM230
Authors: Adams Robyn L. , Adams Ian P. , Lindow Stephen W. , Atkin Stephen L. 
Published: October 2004

Summaryobjective  Somatostatin (SST) modulates exocrine and endocrine secretion, proliferation and apoptosis via five G protein‐linked receptors (SSTRs 1–5). Long‐acting SST analogues such as Octreotide, and the new analogue SOM230, have been developed for the treatment of neuroendocrine tumours. Octreotide has previously been reported to inhibit endothelial proliferation. We wished to determine if SOM230 is a more potent inhibitor of endothelial cell proliferation than Octreotide.design  We have determined the expression of SSTRs in proliferating human umbilical vein endothelial cells (HUVECs) in vitro, and determined their response to the somatostatin analogues SOM230 and Octreotide, following vascular endothelial growth factor (VEGF) stimulation.measurements  Quantitative RT–PCR and western blotting were used to determine the expression of SSTRs 1–5 in proliferating HUVECs. These cells were grown in media containing 200 pg/ml VEGF and treated with 10−11 to 10−6 M Octreotide or SOM230. The WST‐1 assay was then used to determine the effects of these analogues on HUVEC proliferation.results  Using quantitative RT–PCR and western blotting, HUVECs were found to express SSTRs 1, 2 and 5. SSTRs 3 and 4 were not detected. Using the WST‐1 assay, SOM230 was found to significantly inhibit proliferation by up to 46·0% ± 9·4% (10−6–10−7 M; P < 0·05), whereas in parallel studies Octreotide failed to inhibit HUVEC proliferation.conclusions  The pan SST analogue SOM230 inhibits proliferation of HUVECs, which are unaffected by Octreotide. SOM230 may thus represent a suitable candidate drug for antiangiogenic therapy.
Bone mineral density in hyperthyroidism
Authors: Karga Helen , Papapetrou Peter D. , Korakovouni Areti , Papandroulaki Fotini , Polymeris Antony , Pampouras George 
Published: October 2004

Summaryobjective  To investigate whether previous hyperthyroidism is a cause of permanent secondary osteoporosis.design and patients  In this cross‐sectional study, 164 women with untreated or previously treated overt and symptomatic hyperthyroidism were examined 0–31 years after the initial episode of hyperthyroidism and its treatment, and were compared with a control group of 79 age‐matched women without previous history of hyperthyroidism. Subjects with current or previous metabolic bone disease, any antiresorptive treatment for osteoporosis or treatments and habits known to affect bone metabolism were excluded.measurements  The age of the first manifestation of the disease, the age at the measurement of bone mineral density (BMD) at the spine and femoral neck and the interval between diagnosis and treatment of hyperthyroidism and BMD measurement were recorded and the Z‐scores and T‐scores of BMD were analysed.results  Untreated hyperthyroidism and hyperthyroidism up to 3 years after its diagnosis and treatment were associated with decreased BMD. Three or more years after the first episode of the disease the mean Z‐score at both skeletal sites was near zero and not different from the controls. The age at which hyperthyroidism was manifested for the first time had no effect on the final outcome. Women affected at a young age (13–30 years) had a more pronounced loss of BMD when examined untreated or early (< 3 years) after diagnosis, but a BMD significantly above zero if examined later (> 3 years). Older women (aged 51–70 years) showed a similar pattern, although the differences were not significant. Middle‐aged subjects (31–50 years) had the smallest loss of BMD during the first 3 years. Analysis of T‐scores of former hyperthyroid women aged ≥ 51 years showed no significantly different relative risk (RR) for osteoporosis in comparison with the controls. However, the study was not powered enough to give meaningful RR results.conclusions  Overt symptomatic hyperthyroidism is associated with decreased BMD during the first 3 years after diagnosis and treatment of the disease. After this interval, former hyperthyroid women have a Z‐score near zero and not different from women without a history of the disease, apparently because of recovery of the bone density lost early during the course of the disease. Symptomatic hyperthyroidism does not seem to be a cause of long‐lasting osteoporosis, and the age of the patient during the first episode is irrelevant.
Insulin sensitivity in growth hormone‐deficient children: influence of replacement treatment
Authors: Radetti Giorgio , Pasquino Bruno , Gottardi Elena , Contadin Isabella Boscolo , Rigon Franco , Aimaretti Gianluca 
Published: October 2004

Summaryobjective  In adults, excessive GH secretion may lead to secondary diabetes mellitus, while prolonged GH treatment may accelerate the onset of type 2 diabetes mellitus in predisposed children. The aim of the study was to evaluate insulin sensitivity (IS) and glucose tolerance (GT) in a group of GH‐deficient children treated with GH for a period of 6 years.patients and design  One hundred and twenty‐eight children (40 females, 88 males) were included in the study. At the beginning of treatment chronological age was 8·9 ± 3·2 years, height standard deviation score (SDS) −2·43 ± 0·90 and body mass index (BMI) SDS 0·18 ± 1·60. At the end of the study chronological age was 13·0 ± 2·9 years, height SDS −1·24 ± 1·27 and BMI SDS 0·23 ± 1·54. GH was administered at a mean weekly dosage of 0·3 mg/kg, injected subcutaneously over 6–7 days. GT was assessed according to the criteria of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. IS was evaluated with the quantitative insulin sensitivity check index (QUICKI).results  No cases of impaired GT or diabetes were recorded during the follow‐up period. IS, already lower than in controls before starting treatment with GH, decreased significantly during the first year of therapy (QUICKI: 0·346 ± 0·033 vs. 0·355 ± 0·044, P < 0·05), with no further decrease in the following years. No correlation was found between QUICKI, BMI, years of treatment and onset of puberty.conclusions  GH treatment in GH‐deficient children does not lead to an impaired GT or type 2 diabetes mellitus, although it does significantly decrease IS.
Children with congenital hypothyroidism are at risk of adult obesity due to early adiposity rebound
Authors: Wong S. C. , Ng S. M. , Didi M. 
Published: October 2004

Summaryobjective  There is some evidence that children with congenital hypothyroidism (CH) are heavier than their reference population. There are few data on adults with CH. The timing of adiposity rebound (AR) in childhood has been shown to have strong correlations with adult obesity. Our aims were to study the timing of AR and factors affecting AR in children with CH.patients and methods  The timing of AR was examined in a retrospective study of children with CH with growth data at least up to 5 years of age. The proportion of children with CH who reached AR by 37 months and by 49 months of age were compared with healthy children and children with acute lymphoblastic leukaemia (ALL) described in the literature. Correlation of timing of AR with body mass index (BMI) standard deviation score (SDS) at 10 years, initial severity of hypothyroidism and age at normalization of TSH were examined. Multiple logistic regression was used to identify independent factors associated with BMI ≥ 20 (overweight) at 10 years of age.results  The study included 53 children (34 females and 19 males). AR had occurred by 37 months in 37·7% children with CH, in 42·7% children treated for ALL (CH vs. ALL, P = 0·58) and in 4·5% healthy British children (CH vs. normal, P < 0·0001). We found that 54·7% children with CH had reached AR compared with 21·4% of normal children (CH vs. normal, P < 0·0001) by the age of 49 months. Timing of AR showed significant negative correlation with BMI SDS at 10 years (r =−0·487, P = 0·01). There were no significant relationships between timing of AR and initial thyroid function or age at normalization of TSH. Multiple logistic regression analysis identified age at AR as an independent factor associated with BMI ≥ 20 at 10 years of age (P = 0·04).conclusions  Children with CH showed significantly earlier AR compared to normal British children. This showed significant negative correlation with BMI SDS at 10 years. AR in CH does not appear to be directly related to the initial severity of hypothyroidism or to treatment factors.
Assessment of the role of 17β‐oestradiol in bone metabolism in men: does the assay technique matter? The MINOS study
Authors: Szulc Pawel , Claustrat Bruno , Munoz Françoise , Marchand François , Delmas Pierre D. 
Published: October 2004

Summaryobjective  17β‐Oestradiol (17β‐E2), mainly its bioavailable fraction (bio‐17β‐E2), is a determinant of bone mineral density (BMD) and bone remodelling in men. As direct measurement of bio‐17β‐E2 is time‐consuming, we compared the value of directly measured bio‐17β‐E2 and of calculated bio‐17β‐E2 and free 17β‐E2 by studying their association with BMD and markers of bone turnover in a cohort of men (MINOS).design  A cross‐sectional study in which the association between BMD and bone markers, on the one hand, and serum levels of 17β‐E2, on the other, was analysed according to the levels of measured and calculated bio‐17β‐E2 and free 17β‐E2 in a cohort of men.subjects  Men from the MINOS cohort including 87 men aged 19–45 to establish the reference control normal range of hormones and 637 men aged 50–85 (studied group).measurements  Total 17β‐E2, testosterone, SHBG and albumin were measured by standard methods. bio‐17β‐E2 was directly measured after the precipitation of SHBG by ammonium sulfate. bio‐17β‐E2 and free 17β‐E2 were calculated using serum SHBG and albumin levels as described by Södegard et al. (J. Steroid Biochem., 16 (1982) 801).results  Calculated bio‐17β‐E2 and free 17β‐E2 were correlated with measured bio‐17β‐E2 and between themselves (r = 0·90–1·00, P < 0·0001). Calculated bio‐17β‐E2 and free 17β‐E2 disclosed a similar association with BMD (difference between lowest and highest quartiles of 17β‐E2: 2·6–6·8%, P < 0·05–0·005) to that of measured bio‐17β‐E2 (3·6–6·1%, P < 0·005–0·001). The association between bone markers levels and measured vs. calculated 17β‐E2 were also similar. Predictive accuracy for lowered BMD and elevated levels of biochemical bone markers (evaluated using receiver operating characteristics) was relatively low (area under curve −0·582 to 0·709) but similar for different forms of bioavailable and free 17β‐E2.conclusions  In elderly men, the concentrations of bioavailable and free 17β‐E2, calculated using equations including either the measured albumin concentration or the constant albumin concentration of 43 g/l, can be used, at least in clinical studies, instead of the bio‐17β‐E2 concentrations measured after ammonium sulfate precipitation.
Long‐term negative impact on quality of life in patients with successfully treated Cushing's disease
Authors: Heald Adrian H. , Ghosh Sandip , Bray Stephanie , Gibson Christine , Anderson Simon G , Buckler Helen , Fowler Helen L. 
Published: October 2004

Summaryobjective  A cohort of pituitary tumour patients, who had undergone definitive treatment within a 15‐year period at a single neuroscience centre, were investigated as to whether there were differences in psychological well‐being and psychosocial functioning, dependent on endocrine pathology and treatment variables.design  A detailed assessment of 114 patients with benign pituitary tumours in relation to primary diagnosis and mode of treatment was carried out. Psychological rating scales used were: the Hospital Anxiety and Depression Scale − UK version (HADS‐UK), the World Health Organization Quality of Life Scale − abbreviated version (WHOQOL‐BREF), General Health Questionnaire 28 (GHQ‐28), the Functional Assessment of Cancer Therapy (FACT) and the Social Adjustment Scale − modified (SAS1 and SAS2; the former completed by the patient and the latter by another person who knows the patient well). All Cushing's patients were biochemically cured as defined by a normal 24‐h urine free cortisol excretion within the previous 6 months.results  Patients with treated Cushing's disease had significantly impaired psychological well‐being and psychosocial functioning across all tested domains compared with all other pituitary tumours, where scores were similar. When participants with Cushing's disease were excluded, patients who had undergone transfrontal surgery scored significantly higher on GHQ and HADS ratings than transsphenoidally treated patients.conclusion  Cushing's disease even when biochemically stable has long‐term adverse effects on mood and social functioning. We hypothesize that this may be related to irreversible changes in central neural function. Further studies are necessary to define the precise pathways involved.
Ghrelin secretion is inhibited by glucose load and insulin‐induced hypoglycaemia but unaffected by glucagon and arginine in humans
Authors: Broglio Fabio , Gottero Cristina , Prodam Flavia , Destefanis Silvia , Gauna Carlotta , Me Elisa , Riganti Fabrizio , Vivenza Daniela , Rapa Anna , Martina Valentino , Arvat Emanuela , Bona Gianni , Van Der Lely Aart Jan , Ghigo Ezio 
Published: October 2004

Summaryobjective  Circulating ghrelin levels are increased by fasting and decreased by feeding, glucose load, insulin and somatostatin. Whether hyperglycaemia and insulin directly inhibit ghrelin secretion still remains matter of debate. The aim of the present study was therefore to investigate further the regulatory effects of glucose and insulin on ghrelin secretion.design and subjects  We studied the effects of glucose [oral glucose tolerance test (OGTT) 100 g orally], insulin‐induced hypoglycaemia [ITT, 0·1 IU/kg insulin intravenously (i.v.)], glucagon (1 mg i.v.), arginine (0·5 mg/kg i.v.) and saline on ghrelin, GH, insulin, glucose and glucagon levels in six normal subjects.measurements  In all the sessions, blood samples were collected every 15 min from 0 up to + 120 min. Ghrelin, GH, insulin, glucagon and glucose levels were assayed at each time point.results  OGTT increased (P < 0·01) glucose and insulin while decreasing (P < 0·01) GH and ghrelin levels. ITT increased (P < 0·01) GH but decreased (P < 0·01) ghrelin levels. Glucagon increased (P < 0·01) glucose and insulin without modifying GH and ghrelin. Arginine increased (P < 0·01) GH, insulin, glucagon and glucose (P < 0·05) but did not affect ghrelin secretion.conclusions  Ghrelin secretion in humans is inhibited by OGTT‐induced hyperglycaemia and ITT but not by glucagon and arginine, two substances able to increase insulin and glucose levels. These findings question the assumption that glucose and insulin directly regulate ghrelin secretion. On the other hand, ghrelin secretion is not associated with the GH response to ITT or arginine, indicating that the somatotroph response to these stimuli is unlikely to be mediated by ghrelin.
K40E: a novel succinate dehydrogenase (SDH)B mutation causing familial phaeochromocytoma and paraganglioma
Authors: McDonnell Ciara M. , Benn Diana E. , Marsh Deborah J. , Robinson Bruce G. , Zacharin Margaret R. 
Published: October 2004

Summaryobjective  Germline mutations in succinate dehydrogenase (SDH)B, SDHC and SDHD, encoding three of the four subunits of mitochondrial complex II, have been implicated in the tumourigenesis of familial paragangliomas and phaeochromocytomas. Twenty‐three SDHB mutations have been identified to date.patients  We present a novel missense SDHB exon 2 mutation (c.118 A > G; K40E) identified in an Australian family. The proband was diagnosed with phaeochromocytoma at an early age following an unexpected hypertensive crisis and was found to be SDHB mutation‐positive. Subsequent genetic screening of 26 family members has identified 17 mutation‐positive relatives. In addition to the proband, four mutation positive relatives were found to have clinical symptoms or a lesion and/or catecholamine excess after the identification of the mutation led to further evaluation. Both the proband and an uncle have required surgical removal of a tumour.conclusions  This family indicates the importance of germline screening of first‐degree relatives when a patient presents with an apparently sporadic extra adrenal phaeochromocytoma at a young age or whenever a patient with a nonsecretory paraganglioma is found.
Association of serum paraoxonase activity with insulin sensitivity and oxidative stress in hyperthyroid and TSH‐suppressed nodular goitre patients
Authors: Yavuz Dilek Gogas , Yüksel Meral , Deyneli Oguzhan , Ozen Yesim , Aydin Hasan , Akalin Sema 
Published: October 2004

Summaryobjective  Low serum paraoxonase (PON) activity is thought to be a risk factor for the development of atherosclerosis. The present study was designed to evaluate PON1 activity and its relationship with preatherosclerotic markers such as lipid peroxidation and insulin resistance in hyperthyroid patients before and after propylthiouracil (PTU) treatment and in subjects with iatrogenic subclinical hyperthyroidism.patients and design  Twenty patients with hyperthyroidism, 20 patients with euthyroid multinodular goiter (MNG) and 20 age‐ and sex‐matched healthy controls were enrolled in the study. Insulin sensitivity index, PON activity and lipid peroxidation were measured at baseline and 2 months after achieving euthyroidism or subclinical hyperthyroidism. Levothyroxine was given as a part of TSH suppression therapy in multinodular goitre patients.measurements  Insulin sensitivity was determined by an oral glucose tolerance test (OGTT) based on the insulin sensitivity index (ISI) formula, serum paraoxonase activity was determined with a spectrophotometric method. Lipid peroxidation was measured by the formation of thiobarbituric acid reactive substances (TBARs).results  ISI was significantly lower in the hyperthyroid group than baseline levels in MNG patients and controls (P < 0·001). While ISI increased after treatment in the hyperthyroid group (P < 0·01), it significantly decreased with L‐T4 treatment in the MNG group (P < 0·01). Serum paraoxonase activity was significantly lower in the hyperthyroid group before treatment than baseline and final measurements of other groups (P < 0·05). While PON activity increased after restoration of the euthyroid state in the hyperthyroid group (P < 0·05), it decreased with L‐T4 treatment in the MNG group (P < 0·05). Lipid peroxidation was significantly higher in hyperthyroid group compared to baseline levels of other groups (P < 0·05). It decreased after treatment in the hyperthyroid group (P < 0·05) but a significant increase was observed following L‐T4 treatment in the MNG group (P < 0·05). Serum paraoxonase activity was found to be negatively correlated with serum TT4 (r =−0·32, P = 0·003), TT3 levels (r =−0·31, P = 0·004), TBARs levels (r = 0·32, P = 0·003) and positively correlated with ISI (r = 0·35, P = 0·001) and high‐density lipoprotein (HDL) cholesterol levels (r = 0·35, P = 0·0011) in the hyperthyroid and MNG groupsconclusions  Iatrogenic thyroid hormone excess seems to mimic the effects of endogenous thyroid hormone excess on paraoxonase activity, insulin sensitivity and oxidative stress. These findings suggest that TSH suppression with levothyroxine may increase oxidative stress and LDL oxidation and thereby promote atherogenesis.