bluuebunny/crossref_metadata_2025_split huggingface dataset:
Risk‐taking sexual behaviour and self‐reported depression in middle adolescence – a school‐based survey
Authors: Kosunen E. , Kaltiala‐Heino R. , Rimpelä M. , Laippala P. 
Published: August 2003

AbstractBackground Early sexual activity has been widely studied in the context of pregnancies, substance use and antisocial behaviour, but the aspects of psychosexual health have received less attention.Aim To study the associations of early sexual activity and self‐reported depression.Setting A school survey in Finland in 1999 and 2000 in the eighth and ninth grades.Methods Adolescents with experience of sexual intercourse were studied (11 793 girls and 10 443 boys, mean age 15.5 years). Scores of 8 or more in the Beck Depression Inventory were regarded as indicative of self‐reported depression. Associations with sexual behaviour variables were analysed using logistic regression models.Results In both genders, self‐reported depression increased in proportion to the number of sexual partners and with the non‐use of contraception. A higher number of coital experiences correlated with depression only among boys. Adjusting for age and age at menarche/oigarche did not affect the associations detected. In stepwise logistic regression, an increasing number of partners increased the risk for self‐reported depression [for boys with at least five partners odds ratio (OR) 2.5, 95% confidence intervals (CI) 2.2–3.0, and for girls OR 2.7, 95% CI 2.3–3.2]. Boys and girls who did not use contraception showed roughly twice as high a risk as contraceptive users. However, girls with five or more coital experiences had a significantly lower risk for depression compared to girls with only one sexual intercourse.Conclusions Multiple sexual partners and non‐use of contraception may reflect a depressive disorder in both genders. While adolescent health service providers should be aware of the risk for depression among sexually active adolescents, the sexual health of depressed adolescents also warrants special attention.
PPARγ and metabolism: insights from the study of human genetic variants
Authors: Gurnell Mark 
Published: August 2003

SummaryDiabetes, obesity, atherosclerosis and cancer are the principal contributors to morbidity and mortality in Western society. Emerging evidence indicates that a nuclear receptor, the peroxisome proliferator‐activated receptor γ (PPARγ), plays a role in these pathological processes. Furthermore, modulation of receptor action in these diseases may be of therapeutic value, as exemplified by the recent introduction of the thiazolidinediones, a novel class of insulin‐sensitizing agent for the treatment of type 2 diabetes mellitus. The availability of such high‐affinity ligands has facilitated the study of signalling pathways through which PPARγ regulates metabolic processes; these analyses have been complemented by the study of human subjects harbouring (naturally occurring) mutations and polymorphisms within the receptor. The latter have provided unique genetic evidence for a link between PPARγ and mammalian glucose homeostasis, lipid metabolism and regulation of fat mass. This review highlights recent studies which have advanced our understanding of the pivotal role that this receptor plays in metabolism, with particular reference to the consequences of inherited variation in the human receptor gene.
Presence of magnetic resonance imaging abnormalities of the hypothalamic–pituitary axis is a significant determinant of the first 3 years growth response to human growth hormone treatment in prepubertal children with nonacquired growth hormone deficiency
Authors: Zenaty Delphine , Garel Catherine , Limoni Costanzo , Czernichow Paul , Léger Juliane 
Published: August 2003

Summaryobjective The factors influencing the highly variable growth response to GH treatment in GH‐deficient children are not fully understood. Despite a real benefit with GH treatment in term of growth response, most of these patients attain a mean adult height below their target height and the strategy to optimise final height has to be improved. The aim of this study was to investigate whether the presence of congenital abnormalities of the hypothalamic–pituitary axis on magnetic resonance imaging (MRI) could be a determinant of the growth response in nonacquired prepubertal GH‐deficient children, and to identify which pretreatment variables most significantly affect the first 3 years growth response to human GH (hGH) therapy.patients and methods The growth response to hGH treatment (0·55 ± 0·1 IU/kg/week) was evaluated in 69 prepubertal children with nonacquired GH deficiency, according to the absence (group A: chronological age = 4·8 ± 2·4 years, n= 37) or the presence (group B: chronological age = 3·4 ± 2·7 years, n= 32) of developmental abnormalities on cerebral magnetic imaging and, after controlling for GH dose, age, height, height velocity (SDS) and body mass index at start of treatment, maximum stimulated GH peak concentration, GH deficiency type (isolated vs. multiple deficiency), parental height, size at birth and sex.results After 3 years of treatment, the mean height gain was significantly higher in patients of group B vs. group A (2·2 ± 1·3 vs. 1·6 ± 1 SDS; P < 0·05). In a multiple regression analysis, age (r2 = 0·19, negatively correlated), pretreatment height velocity (r2 = 0·11, negatively correlated), GH dose (r2 = 0·05, positively correlated) and presence of magnetic resonance imaging developmental abnormalities (r2 = 0·05, positively correlated) were found to significantly explain 40% of the variability in growth response.conclusions The detection of congenital abnormalities in the hypothalamic–pituitary area on MRI is more important than the level of maximum stimulated GH to predict the growth response to hGH treatment in prepubertal nonacquired GH‐deficient children. Although the persistence of GH deficiency remains to be confirmed during follow‐up by reassessment of GH secretion in isolated GH‐deficient patients with normal MRI findings, further studies are needed to evaluate whether an increased hGH dose in these patients could improve long‐term growth response.
Insulin resistance and β‐cell dysfunction in normoglycaemic European women with a history of gestational diabetes
Authors: Kousta Eleni , Lawrence Natasha J. , Godsland Ian F. , Penny Anna , Anyaoku Victor , Millauer Barbara A. , Cela Ester , Johnston Desmond G. , Robinson Stephen , McCarthy Mark I. 
Published: August 2003

Summaryobjective Women with previous gestational diabetes (GDM) are at increased risk of subsequent type 2 diabetes. To characterize early metabolic abnormalities associated with this increased risk, we studied normoglycaemic women with a history of GDM.patients and measurements We performed an insulin‐modified, frequently sampled intravenous glucose tolerance test (FSIVGTT) in 34 normoglycaemic European women with previous GDM and 44 European control women, deriving measures of insulin sensitivity, glucose effectiveness, glucose disappearance rate and acute insulin response to glucose.results Post‐GDM women were more obese than controls [body mass index (BMI), geometric mean (95% confidence interval); 25·3 kg/m2 (23·8–27·1 kg/m2) vs. 23·1 kg/m2 (21·9–24·3 kg/m2), P = 0·03]. Evidence of insulin resistance was provided by their lower insulin sensitivity as measured by FSIVGTT [0·6 × 10−4/min/pmol/l (0·3–1·2 × 10−4/min/pmol/l) vs. 1·5 × 10−4/min/pmol/l (1·2–1·8 × 10−4/min/pmol/l), P = 0·01] and by homeostatic model assessment [72% (49–107%) vs. 153% (113–206%), P = 0·004]; and by their higher fasting triglycerides [1·0 mmol/l (0·7–1·5 mmol/l) vs. 0·7 mmol/l (0·6–0·8 mmol/l), P = 0·001]. Though there was no difference between groups in fasting NEFA levels, acute NEFA suppression was diminished in the post‐GDM group (P = 0·01). Concomitant β‐cell dysfunction in the post‐GDM women was revealed by their lower disposition index [0·05/min (0·02–0·10/min) vs. 0·11/min (0·09–0·14/min), P = 0·02] compared to controls. The differences in insulin sensitivity, but not those of β‐cell function, were partly, though not completely, attributable to differences in regional and total adiposity.conclusions European normoglycaemic women with previous GDM display both glucoregulatory and antilipolytic insulin resistance, reduced β‐cell function and dyslipidaemia. These metabolic abnormalities are likely to contribute to their increased risk of future type 2 diabetes.
Maternal hypothyroxinaemia during early pregnancy and subsequent child development: a 3‐year follow‐up study
Authors: Pop Victor J. , Brouwers Evelien P. , Vader Huib L. , Vulsma Thomas , Van Baar Anneloes L. , De Vijlder Jan J. 
Published: August 2003

Summaryobjective To evaluate the impact of maternal hypothyroxinaemia during early gestation (fT4 below the lowest tenth percentile and TSH within the reference range: 0·15–2·0 mIU/l) on infant development, together with any subsequent changes in fT4 during gestation.design A prospective 3‐year follow‐up study of pregnant women and their children up to the age of 2 years.measurements Child development was assessed by means of the Bayley Scales of Infant Development in children of women with hypothyroxinaemia (fT4 below the tenth percentile at 12 weeks’ gestation) at 12 weeks’ gestation (cases), and in children of women with fT4 between the 50th and 90th percentiles at 12 weeks’ gestation, matched for parity and gravidity (controls). Maternal thyroid function (fT4 and TSH) was assessed at 12, 24 and 32 weeks’ gestation. The mental and motor function of 63 cases and 62 controls was compared at the age of 1 year, and of 57 cases and 58 controls at the age of 2 years.results Children of women with hypothyroxinaemia at 12 weeks’ gestation had delayed mental and motor function compared to controls: 10 index points on the mental scale (95% CI: 4·5–15 points, P = 0·003) and eight on the motor scale at the age of 1 year (95% CI: 2·3–12·8 points, P = 0·02), as well as eight index points on the mental (95% CI: 4–12 points, P = 0·02), and 10 on the motor scale (95%CI: 6–16 points, P = 0·005) at the age of 2 years. Children of hypothyroxinaemic women in whom the fT4 concentration was increased at 24 and 32 weeks’ gestation had similar scores to controls, while in the controls, the developmental scores were not influenced by further declines in maternal fT4 at 24 and 32 weeks’ gestation.conclusions Maternal hypothyroxinaemia during early gestation is an independent determinant of a delay in infant neurodevelopment. However, when fT4 concentrations increase during pregnancy in women who are hypothyroxinaemic during early gestation, infant development appears not to be adversely affected.
Epidemiological survey of thyroid volume and iodine intake in schoolchildren, postpartum women and neonates living in Ulaan Baatar
Authors: Fuse Yozen , Igari Tomoyuki , Yamada Chieri , Sakano Shoji , Ito Harumichi , Umenai Takusei , Irie Minoru 
Published: August 2003

Summaryobjective  Although endemic goiter had been recognized in most parts of the country, there are few available data on iodine‐deficiency disorders (IDDs) in Mongolia. This study aimed to characterize the current status of iodine deficiency in Ulaan Baatar, Mongolia's capital city.design  Cross‐sectional, observational study designed and performed according to the surveillance methods for IDD prevalence recommended by WHO/UNICEF/ICCIDD.subjects  A total of 505 schoolchildren aged 9–14 years (237 girls and 268 boys) and 138 mothers and their neonatal infants were selected to clinical and biochemical examination of the thyroid in 1996 and 1999.measurements  The anthropometric measurements, thyroid volume determined by ultrasound, blood TSH and FT4 concentrations, urinary iodine concentration and iodine content of salt consumed in households.results  Median thyroid volumes based on age were generally higher than those in iodine‐sufficient areas and comparative to those reported in mild iodine‐deficiency areas. Application of the updated WHO/ICCIDD reference values in iodine‐replete European schoolchildren to the Mongolian children aged 10–12 years resulted in a goiter prevalence of 43·3%. The median value of urinary iodine concentration was 152·5 µg/l (1·20 µmol/l) and 40·3% of children excreted iodine below 100 µg/l. Iodized salt (> 40 ppm) was consumed in 63·1% of households and in the children using noniodized salt their urinary iodine concentration was lower than those using ionized salt. In postpartum women, median thyroid volume and urinary iodine concentration were 11·3 ml and 107 µg/l (0·84 µmol/l), respectively, and 46% of women excreted less than 100 µg/l (0·79 µmol/l) of iodine. Of their neonates, 17·8% had elevated blood TSH levels (> 5 mU/l). In a 1999 survey, the goiter prevalence and ratio of low iodine excretion in schoolchildren decreased to 29·8% and 31·3%, respectively, while median urinary iodine concentration remain unchanged (160 µg/l; 1·26 µmol/l).conclusion  The present study clearly indicates the presence of mild iodine deficiency in Mongolia. Enlarged thyroid gland and normal iodine excretion observed in schoolchildren living in Ulaan Baatar may result from the residual effects of iodine deficiency previously and presumably still exist in the city. Slight reduction in the rate of children with enlarged thyroid and low urinary iodine excretion after the onset of national iodinization programme suggests incomplete normalization of thyroid volume in children and that the correction of iodine deficiency is now in progress in Ulaan Baatar. Further nationwide surveys together with monitoring the progress of the national programme eliminating IDD are required in suburban areas surrounding the city and also in rural areas.
Usefulness of the free α‐subunit to diagnose hypogonadotropic hypogonadism
Authors: Mainieri Alberto Scofano , Elnecave Regina Helena 
Published: August 2003

Summaryobjective Differentiating constitutional delay of growth and puberty from hypogonadotropic hypogonadism is still a problem in clinical practice. Our previous study demonstrated that the peak/basal ratio of the free α‐subunit of the glycoprotein hormones is higher in normal prepubertal boys than in male adults with hypogonadotropic hypogonadism. The objective of this study was to assess the performance of this ratio in normal male patients at different ages and levels of pubertal development, and in patients with hypogonadotropic hypogonadism, both isolated and combined with other pituitary hormone deficiencies.design Cohort study.patients Twenty‐eight normal prepubertal males between 6 and 8 years; 20 normal prepubertal males between 9 and 13 years; 18 males with constitutional delay of growth and puberty; 26 normal pubertal males; 13 adult men with isolated hypogonadotropic hypogonadism; 21 adult men with complete hypogonadotropic hypogonadism combined with other hormone deficiencies; and 11 adult men with partial hypogonadotropic hypogonadism combined with other hormone deficiencies.measurements Serum levels of free α‐subunit immediately before (basal), and 30 and 60 min after 100 µg intravenous GnRH were measured by immunofluorimetry. Median and P25–P75 range of the peak/basal ratio of the free α‐subunit was determined for each group. A receiver operating characteristics curve was calculated. Results were compared using the Kruskal–Wallis test.results The peak/basal ratio of the free α‐subunit was higher in patients with constitutional delay of growth and puberty (7·46) than in those with isolated hypogonadotropic hypogonadism (2·73), complete combined hypogonadotropic hypogonadism (1·58), and partial combined hypogonadotropic hypogonadism (2·61; P < 0·001). A peak/basal ratio < 3·26 identified hypogonadotropic hypogonadism with 93·2% sensitivity and 94·4% specificity when compared to constitutional delay of growth and puberty. There was no statistical difference between the peak/basal ratio of prepubertal patients between 6 and 8 years (7·20), patients between 8 and 13 years (8·71), normal pubertal males (8·10) and those with constitutional delay of growth and puberty (7·46). In a group of boys with delayed puberty, a cut‐off point of 3·69 defined hypogonadotropic hypogonadism with 95·6% sensitivity and 94·4% specificity. A cut‐off point of 4·81 gave 100% sensitivity (88·9% specificity), and 3·09 gave 100% specificity (86·7% sensitivity).conclusions The peak/basal ratio of the free α‐subunit can be used for the differential diagnosis of constitutional delay of growth and puberty and hypogonadotropic hypogonadism, irrespective of age. This distinction allows early investigation and treatment of patients with hypogonadotropic hypogonadism and reassurance for those with constitutional delay of growth and puberty.
Alprazolam (a benzodiazepine activating GABA receptor) reduces the neuroendocrine responses to insulin‐induced hypoglycaemia in humans
Authors: Giordano Roberta , Grottoli Silvia , Brossa PierClaudio , Pellegrino Micaela , Destefanis Silvia , Lanfranco Fabio , Gianotti Laura , Ghigo Ezio , Arvat Emanuela 
Published: August 2003

Summaryobjective Alprazolam (ALP), a benzodiazepine‐activating GABAergic receptor, possesses clear centrally mediated inhibitory effects on ACTH and cortisol secretion that could reflect an inhibitory influence on CRH‐ and/or AVP‐secreting neurones. An inhibitory effect of ALP on catecholamine release has also been shown while its effect on GH secretion is unclear. To further clarify the neuroendocrine actions of ALP, we studied the ALP effects on the neurohormonal responses to hypoglycaemia in a group of normal subjects.design In eight normal subjects [four women and four men, 22–34 years old, body mass index (BMI) 20–25 kg/m2] the ACTH, cortisol, GH, adrenaline (A) and noradrenaline (NA) responses to insulin‐induced hypoglycaemia [ITT, 0·1 UI/kg regular insulin intravenously (i.v.) at 0 min] preceded by placebo or ALP (0·02 mg/kg orally at −90 min) were studied in two sessions at least 10 days apart.measurements Blood samples were taken basely at −90 and 0 min and every 15 min up to +120 min. ACTH, cortisol, GH, A and NA level were assayed at each time point in both sessions.results All subjects experienced hypoglycaemia (plasma glucose levels below 2·2 mmol/l). After placebo ITT induced clear‐cut increases in ACTH (peak vs. baseline, mean ± SEM: 27·9 ± 3·9 vs. 7·1 ± 1·5 pmol/l), cortisol (438·1 ± 32·0 vs. 237·7 ± 19·3 nmol/l) and GH (38·1 ± 9·7 vs. 5·7 ± 2·0 µg/l) levels (P < 0·05). Marked increase in A (6627·2 ± 116·7 vs. 263·7 ± 71·4 pmol/l) and NA (3·8 ± 1·5 vs. 1·6 ± 1·0 nmol/l) levels were also recorded (P < 0·05). Pretreatment with ALP significantly inhibited the ACTH peak response to ITT (17·8 ± 5·0 pmol/l, P < 0·05), while the cortisol response showed a non significant reduction (342·1 ± 38·7 nmol/l). ALP also significantly reduced the GH (21·7 ± 4·7 µg/l, P < 0·02) and A (3828·0 ± 1400·7 pmol/l, P < 0·02) responses to ITT. On the contrary, ALP lowered basal NA levels (P < 0·05) but did not significantly affect its response to ITT (2·2 ± 1·2 nmol/l). Glucose changes induced by ITT were not modified by ALP.conclusions This study shows that GABAergic activation by alprazolam significantly inhibits the neuroendocrine and adrenomedullary responses to hypoglycaemia.
Peripheral parameters of oxidative stress in Graves’ disease: the effects of methimazole and 131 iodine treatments
Authors: Abalovich M. , Llesuy S. , Gutierrez S. , Repetto M. 
Published: August 2003

Summarybackground Increased oxidative stress, with elevated levels of free radicals, together with diminished antioxidation have been described previously in models of hyperthyroidism and in patients with Graves’ disease. However, controversial results have been found about the antioxidant status and its response to treatment.aim To evaluate the antioxidant/oxidant balance in active Graves’ disease and the effects of treatment with methimazole (MMI) and 131 iodine (131I).patients and methods We studied 69 hyperthyroid (H) patients, 58 female and 11 male, 16–50 years old; total T3: 8 ± 2 nmol/l, total T4: 264 ± 65 nmol/l (all mean ± SD), TSH: 0·1 ± 0·1 mIU/l, TSH receptor antibody 41 ± 21%, highest 131Iodine uptake: 67 ± 16%. As a control group (C), 19 normal adults were studied.design Parameters evaluated were: tert‐butyl hydroperoxide initiated chemiluminiscence (CL), superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), glutathione peroxidase (GPx) and total reactive antioxidant potential (TRAP).results In patients vs. controls there was an increase in CL levels (6207 ± 1434 vs. 3000 ± 851 cpm/mg of haemoglobin, P < 0·001), decrease in SOD (0·4 ± 0·1 vs. 0·7 ± 0·2 U/mg prot, P < 0·05; corresponding to 0·15 µg/ml), CAT (2·8 ± 0·6 vs. 3·8 ± 0·7 pmol/mg prot, P < 0·001) and GSH (1·2 ± 0·4 vs. 2 ± 0·7 mmol/l erythrocytes, P < 0·05). The decrease in GPx and TRAP did not show significant differences. The parameters were also recorded in 30 patients who became euthyroid after treatment: 20 of them under MMI therapy (2–12 months) and the rest 3–6 months after 131Iodine administration. All the parameters evaluated were normalized after MMI; however, CL levels stayed high after 131I and only CAT and GSH levels returned to normal values.conclusion Our results confirm the imbalance of the antioxidant/oxidant status in hyperthyroid patients. MMI treatment was more effective than 131I therapy to improve that balance. We speculate on the benefits of antioxidant therapy administrated together with the habitual treatment of hyperthyroidism, especially in patients after 131I therapy.
Reduced expression of the growth hormone and type 1 insulin‐like growth factor receptors in human somatotroph tumours and an analysis of possible mutations of the growth hormone receptor
Authors: Kola Blerina , Korbonits Márta , Diaz‐Cano Salvador , Kaltsas Gregory , Morris Damian G. , Jordan Suzanne , Metherell Lou , Powell Michael , Czirják Sándor , Arnaldi Giorgio , Bustin Stephen , Boscaro Marco , Mantero Franco , Grossman Ashley B. 
Published: August 2003

Summaryobjective Clinical acromegaly is characterized by elevated GH secretion in the presence of high circulating IGF‐I levels. We hypothesized that the physiological IGF‐I/GH negative feedback loop may be reset in somatotroph adenomas, specifically in terms of the level of expression of these receptors or mutations of the GH receptor (GH‐R) in such tumours.methods We therefore investigated the full coding sequence of the GH‐R in a series of somatotroph and other pituitary adenomas. We also investigated the mRNA expression of these putative feedback receptors in a series of pituitary adenomas and normal pituitary tissue, and their protein expression by immunostaining. Real‐time RT–PCR assay was used for the quantification of the type 1 IGF receptor (IGF‐R) and GH receptor (GH‐R) mRNA, and sequence analysis was performed on the coding region of the GH‐R gene.results No somatic mutations of the GH‐R mRNA were detected in 18 GH‐secreting tumours or two nonfunctioning pituitary adenomas (NFPAs). However, the levels of GH‐R mRNA were significantly lower in both somatotroph tumours and NFPAs compared to the normal pituitary (P < 0·05 for both). Immunostaining for GH‐R also showed significantly less GH‐R expression in somatotroph adenomas compared to normal pituitary tissue (P < 0·0001). IGF‐R mRNA levels were significantly lower in somatotroph tumours compared to normal pituitary (P = 0·005), and trended lower in corticotroph tumours (P = 0·07), while the other tumour types showed no significant difference from normal pituitary. Immunostaining for IGF‐R also showed less IGF‐R protein in the somatotroph adenomas compared to the normal pituitary tissue (P < 0·01).conclusions Our findings suggest that decreased feedback inhibition of GH because of somatic mutations of the coding region of the GH‐R are unlikely to be a common factor in the pathogenesis of these tumours. Nevertheless, decreased expression of the GH‐R and of IGF‐R in somatotroph tumours (both at the mRNA and protein level) may, at least in part, help explain the continuous secretion of GH from the tumour despite the high circulating levels of IGF‐I and GH.