bluuebunny/crossref_metadata_2025_split huggingface dataset:
High dose estrogen treatment increases bone mineral density in male-to-female transsexuals receiving gonadotropin-releasing hormone agonist in the absence of testosterone
Authors: Mueller Andreas , Dittrich Ralf , Binder Helge , Kuehnel Werner , Maltaris Theodoros , Hoffmann Inge , Beckmann Matthias W 
Published: July 2005

Objective: To study the effect of estrogen (E) on the male skeleton in the absence of testosterone (T).
Design: Retrospective analyses of 40 middle-aged transsexuals treated with subcutaneous injections of gonadotropin-releasing hormone agonist every 4 weeks and oral 17-beta-estradiol-valerat 6 mg/day over two years until reassignment surgery.
Methods: The bone mineral density (BMD) in the femoral neck and lumbar spine (L2–L4) was measured with dual-energy X-ray absorptiometry at the beginning of cross-sex hormone treatment, after 12 and 24 months, and serum T, E, sex hormone-binding globulin (SHBG), calcitonin (CAL), osteocalcin (OSC), and urinary free deoxypyridinoline (DPD) were measured.
Results: After 12 months, a significant increase in BMD in the lumbar spine from 1.2 to 1.234 g/cm2 and after 24 months to 1.274 g/cm2 was observed. There was a significant increase in BMD in the femoral neck area from 1.068 to 1.109 g/cm2 after 24 months. There was a significant decrease in serum T levels from 18.65 to 0.57 nmol/l after 12 months, and to 0.62 nmol/l after 24 months, a significant increase in SHBG levels from 50.09 to 125 nmol/l after 12 months, and to 130 nmol/l after 24 months, and a significant increase in serum E levels from 73.42 to 881.6 pmol/l after 12 months, and to 923.62 pmol/l after 24 months of cross-sex hormone treatment. Serum levels of CAL, OSC and urinary DPD were unchanged.
Conclusion: We conclude that high dose E treatment is able to increase BMD significantly in the femoral neck and lumbar spine independently of serum T levels in middle-aged men. There is no risk of osteoporosis developing in male-to-female transsexuals receiving GnRHa when there is an adequate E substitution.
Mutational spectrum of steroid 21-hydroxylase and the genotype-phenotype association in Middle European patients with congenital adrenal hyperplasia
Authors: Dolž;an V , Sólyom J , Fekete G , Kovács J , Rakosnikova V , Votava F , Lebl J , Pribilincova Z , Baumgartner-Parzer SM , Riedl S , Waldhauser F , Frisch H , Stopar-Obreza M , Krž;išnik C , Battelino T 
Published: July 2005

Objective: To analyze the mutational spectrum of steroid 21-hydroxylase (CYP21) and the genotype– phenotype correlation in patients with congenital adrenal hyperplasia (CAH) registered in the Middle European Society for Pediatric Endocrinology CAH database, and to design a reliable and rational approach for CYP21 mutation detection in Middle European populations.
Design and methods: Molecular analysis of the CYP21 gene was performed in 432 CAH patients and 298 family members. Low-resolution genotyping was performed to detect the eight most common point mutations. High-resolution genotyping, including Southern blotting and sequencing was performed to detect CYP21 gene deletions, conversions, point mutations or other sequence changes.
Results: CYP21 gene deletion and In2 and Ile172Asn mutation accounted for 72.7% of the affected alleles in the whole study group. A good genotype–phenotype correlation was observed, with the exception of Ile172Asn and Pro30Leu mutations. In 37% of patients low resolution genotyping could not identify the causative mutation or distinguish homozygosity from hemizygosity. Using high-resolution genotyping, the causative mutations could be identified in 341 out of 348 analyzed patients. A novel mutation Gln315Stop was found in one simple virilising CAH (SV-CAH) patient from Austria. In the remaining seven patients polymorphisms were identified as the leading sequence alteration. The presence of elevated basal and ACTH-stimulated 17-hydroxyprogesterone, premature pubarche, advanced bone age and clitoral hypertrophy directly implicated Asn493Ser polymorphism in the manifestation of nonclassical- (NC) and even SV-CAH.
Conclusions: By genotyping for the most common point mutations, CYP21 gene deletion/conversion and the 8 bp deletion in exon 3, it should be possible to identify the mutation in 94–99% of the diseased alleles in any investigated Middle European population. In patients with a mild form of the disease and no detectable mutation CYP21 gene polymorphisms should be considered as a plausible disease-causing mutation.
Endoplasmic reticulum stress induces Wfs1 gene expression in pancreatic β-cells via transcriptional activation
Authors: Ueda Kohei , Kawano June , Takeda Komei , Yujiri Toshiaki , Tanabe Katsuya , Anno Takatoshi , Akiyama Masaru , Nozaki Junichi , Yoshinaga Takeo , Koizumi Akio , Shinoda Koh , Oka Yoshitomo , Tanizawa Yukio 
Published: July 2005

Objective: TheWFS1gene encodes an endoplasmic reticulum (ER) membrane-embedded protein. HomozygousWFS1gene mutations cause Wolfram syndrome, characterized by insulin-deficient diabetes mellitus and optic atropy. Pancreatic β-cells are selectively lost from the patient’s islets. ER localization suggests that WFS1 protein has physiological functions in membrane trafficking, secretion, processing and/or regulation of ER calcium homeostasis. Disturbances or overloading of these functions induces ER stress responses, including apoptosis. We speculated that WFS1 protein might be involved in these ER stress responses.Design and methods: Islet expression of the Wfs1 protein was analyzed immunohistochemically. Induction of Wfs1 upon ER stress was examined by Northern and Western blot analyses using three different models: human skin fibroblasts, mouse pancreatic β-cell-derived MIN6 cells, and Akita mouse-derivedIns296Y/Yinsulinoma cells. The humanWFS1gene promoter-luciferase reporter analysis was also conducted.Result: Islet β-cells were the major site ofWfs1expression. This expression was also found in δ-cells, but not in α-cells.WFS1expression was transcriptionally up-regulated by ER stress-inducing chemical insults. Treatment of fibroblasts and MIN6 cells with thapsigargin or tunicamycin increasedWFS1mRNA. WFS1 protein also increased in response to thapsigargin treatment in these cells.WFS1gene expression was also increased inIns296Y/Yinsulinoma cells. In these cells, ER stress was intrinsically induced by mutant insulin expression. TheWFS1gene promoter-luciferase reporter system revealed that the humanWFS1promoter was activated by chemically induced ER stress in MIN6 cells, and that the promoter was more active inIns296Y/Ycells thanIns2wild/wildcells.Conclusion:Wfs1expression, which is localized to β- and δ-cells in pancreatic islets, increases in response to ER stress, suggesting a functional link betweenWfs1and ER stress.
Efficacy of chimeric molecules directed towards multiple somatostatin and dopamine receptors on inhibition of GH and prolactin secretion from GH-secreting pituitary adenomas classified as partially responsive to somatostatin analog therapy
Authors: Jaquet P , Gunz G , Saveanu A , Dufour H , Taylor J , Dong J , Kim S , Moreau J-P , Enjalbert A , Culler M D 
Published: July 2005

Objective: This study compared the potency of a somatostatin receptor (sstr)2–sstr5 analog, BIM-23244, of an sstr2-dopamine D2 receptor (sstr2-DAD2) molecule, BIM-23A387 and of new somatostatin-dopamine chimeric molecules with differing, enhanced affinities for sstr2, sstr5 and DAD2, BIM-23A758, BIM-23A760 and BIM-23A761, to suppress GH and prolactin (PRL) from 18 human GH adenomas that are partially responsive to octreotide or lanreotide.Materials and methods: The sstr2, sstr5 and DAD2 mRNA levels were determined by RT-PCR. The effect of drugs was tested in cell cultures at various concentrations.Results: In all tumors, the sstr2, sstr5 and DAD2 mRNA levels were coexpressed (mean levels±s.e.m.0.4±0.1, 5.3±1.9 and 2.0±0.4 copy/copy β-glucuronidase). In 13 tumors, the maximal suppression of GH secretion produced by BIM-23A387 (30±3%) and BIM-23244 (28±3%) was greater than that produced by octreotide (23±3%). In six out of 13 tumors, BIM-23A758, BIM-23A760 and BIM- 23A761 produced greater maximal suppression of GH secretion than octreotide (33±5, 38±2 and 41±2 vs 24±2%). Their EC50values were 10, 2 and 4 pmol/l. BIM-23A761 was more effective than BIM-23A387 in GH suppression (41±2 vs 32±4%). The new chimeric molecules produced maximal PRL suppression greater than octreotide (62±8 to 74±5 vs 46±11%).Conclusions: Novel dopamine-somatostatin chimeric molecules with differing, enhanced activity at sstr2, sstr5 and DAD2, consistently produced significatly greater suppression of GH and PRL than either octreotide or single-receptor-interacting ligands in tumors from patients classified as only partially responsive to octreotide therapy. The higher efficacy of the chimeric compounds was, at least partially, linked to their high affinity for sstr2 (IC501–10 pmol/l). The other mechanisms by which such molecules produce an enhanced inhibition of GH remain to be elucidated.
Children's Residential Weight-Loss Programs Can Work: A Prospective Cohort Study of Short-Term Outcomes for Overweight and Obese Children
Authors: Gately Paul J. , Cooke Carlton B. , Barth Julian H. , Bewick Bridgette M. , Radley Duncan , Hill Andrew J. 
Published: July 2005

Objective. The evidence base for child obesity treatment is weak. Children's weight-loss camps, despite their popularity, have not been properly evaluated. This study evaluated the effectiveness of a residential weight-loss camp program for overweight and obese children.
Methods. A total of 185 overweight children (mean age: 13.9 years) enrolled in 1 of 4 consecutive programs between 1999 and 2002 (intervention group) were compared with 94 children of similar ages who were not camp attendees, ie, 38 overweight children and 56 normal-weight children. The intervention group attended a 6-week (maximum) summer residential weight-loss camp. The program included a daily schedule of six 1-hour, skill-based, fun, physical activity sessions, moderate dietary restriction, and group-based educational sessions. All children were assessed for body weight, height, and other anthropometric measures, blood pressure, aerobic fitness, self-esteem, and selected sports skills.
Results. Campers, who stayed for a mean of 29 days, lost 6.0 kg, reduced their BMI by 2.4 units, and reduced their BMI SD scores by 0.28. Fat mass decreased significantly (from 42.7 to 37.1 kg), whereas fat-free mass did not change. In contrast, both comparison groups gained weight during this period. Camp attendees also showed significant improvements in blood pressure, aerobic fitness, and self-esteem. Longer durations of stay were associated with greater improvements in outcomes.
Conclusions. In the short term at least, this weight-loss program was effective across a range of health outcomes. Ongoing research is examining the maintenance of these improvements. Future research should investigate whether benefits can be generalized across weight-loss camps and how the intervention can be adapted to nonresidential, term-time settings.
Effects of Atomoxetine on Growth After 2-Year Treatment Among Pediatric Patients With Attention-Deficit/Hyperactivity Disorder
Authors: Spencer Thomas J. , Newcorn Jeffrey H. , Kratochvil Christopher J. , Ruff Dustin , Michelson David , Biederman Joseph 
Published: July 2005

Objective. Treatment for attention-deficit/hyperactivity disorder is maintained typically over periods of months or years and, as a result, the potential effects on growth of pharmacotherapy for this disorder have been an area of concern. This meta-analysis examined the effect on growth of atomoxetine, now approved in the United States for the treatment of attention-deficit/hyperactivity disorder.
Methods. Patients (N = 412) were 6 to 16 years of age at the start of the treatment period and received atomoxetine treatment (maximal dose: 1.8 mg/kg per day) for ≥2 years. Weight and height measurements were analyzed both as actual values and after conversion to percentiles and z scores with growth charts from the Centers for Disease Control and Prevention. Expected weight and height at the end point were calculated through extrapolation from patients' baseline percentiles with the growth charts.
Results. Results indicated that, after 2 years, observed weight and height were close to those predicted on the basis of the patients' baseline weight and height. Weight increased an average of 10.8 kg, a decrease relative to baseline normative weight of 2.7 percentiles, corresponding to 0.87 kg. Height increased an average of 13.3 cm, a decrease relative to baseline normative heights of 2.2 percentiles, corresponding to 0.44 cm. For both weight and height, the quartile of patients who were smallest at baseline had an increase in end-point percentile, whereas patients in the highest quartile had a decrease.
Conclusions. These findings suggested that, at the group level, there was only a minimal effect on height after 2 years of treatment with atomoxetine and, for patients most at risk (the lowest quartile), there seemed to be no effect.
Effect of Nutrition on Growth in Short Stature Before and During Growth-Hormone Therapy
Authors: Zadik Zvi , Sinai Tali , Zung Amnon , Reifen Ram 
Published: July 2005

Objective. Although nutritional counseling is an integral part of the management of rapidly growing children, few studies have focused on the importance of nutritional supervision during growth-hormone (GH) therapy. The objective of this study was to study the effect of caloric intake on growth before and during GH therapy.Methods. A total of 115 short normal prepubertal children who were 7.4 ± 1.2 years of age (mean ± SD) and had height SD score (SDS) of −2.5 ± 0.6 were treated with a GH dose range of 0.13 to 0.52 mg/kg per week for 1 year. A 3-day nutritional recall and blood chemistry analysis were repeated every 3 months.Results. Caloric intake (expressed as % recommended dietary allowance) was positively correlated with the pretreatment growth velocity (SDS) and the increment in growth velocity SDS during the first year of GH therapy (r = 0.363 and 0.493). By stepwise regression analysis, we identified 4 parameters that could predict the 1-year increment in growth velocity SDS: the contribution of each factor (% variability) was pretreatment growth velocity SDS 36%, GH dose (27%), caloric intake 4%, and the integrated concentration of GH 2% (r2 = 0.689). GH therapy induced an alkaline phosphatase increment of 59 ± 49 IU/mL, an insulin-like growth factor-I increment of 32.6 ± 11.9 nmol/L, and a GH binding protein increment of 10.2 ± 2.7%. During GH therapy, an increase in serum transferrin (56.5 ± 35.2 mg/dL) and a decrease in serum iron (20.5.5 ± 20.2 μg/dL) were noted. These changes could not be detected through hemoglobin levels or hematopoietic indexes. Dietary iron supplementation reversed this phenomenon.Conclusions. The nutritional status of GH-treated patients before and throughout the course of GH treatment should be monitored closely to improve the growth response and prevent nutritional deficiencies. Special emphasis should be placed on iron nurture.
The Incidence and Course of Retinopathy of Prematurity: Findings From the Early Treatment for Retinopathy of Prematurity Study
Authors:   Early Treatment for Retinopathy of Prematurity Cooperative Group
Published: July 2005

Objectives. To estimate the incidence of retinopathy of prematurity (ROP) in the Early Treatment for Retinopathy of Prematurity (ETROP) Study and compare these results with those reported in the Cryotherapy for Retinopathy of Prematurity (CRYO-ROP) Study.
Methods. The ETROP Study, as part of its protocol, screened 6998 infants at 26 centers throughout the United States. Serial eye examinations were conducted for infants born weighing &lt;1251 g, making it possible to estimate the frequency of ROP in different birth weight and gestational age categories. ROP was categorized according to the International Classification for ROP.
Results. The incidence of any ROP was 68% among infants of &lt;1251 g. The findings were compared with those for infants born in 1986 and 1987 in the CRYO-ROP Study. The overall incidences of ROP were similar in the 2 studies, but there was more zone I ROP in the ETROP Study. Among infants with ROP, more-severe ROP (prethreshold) occurred for 36.9% of infants in the ETROP Study and 27.1% of infants in the CRYO-ROP Study. The gestational age of onset of ROP of different severities has changed very little since the CRYO-ROP Study was conducted.
Conclusions. ROP remains a common important problem among infants with birth weights of &lt;1251 g. The incidence of ROP, time of onset, rate of progression, and time of onset of prethreshold disease have changed little since the CRYO-ROP natural-history study.
Frequency of Fungemia in Hospitalized Pediatric Inpatients Over 11 Years at a Tertiary Care Institution
Authors: Abelson Jonathan A. , Moore Theodore , Bruckner David , Deville Jaime , Nielsen Karin 
Published: July 2005

Objectives. To determine the frequency of bloodstream fungal infections in children who were admitted to our tertiary institution over an 11-year period.
Methods. We conducted a retrospective cohort study of patients who were aged 0 to 21 years, had bloodstream fungal infections, and were admitted to the University of California, Los Angeles from 1991 through 2001. Patients were identified through the microbiology laboratory database. All positive fungal cultures for pediatric inpatients were reviewed. For each fungemic patient, a review of clinical course, cause, and outcome was performed.
Results. Over 11 years, 1124 pediatric inpatients with 3633 positive cultures had evidence of fungal colonization or infection. The mean incidence of positive fungal cultures increased from 105 between 1991 and 1996 to 129 patients per year between 1997 and 2001. Fungal isolates were mainly Candida species (85%) obtained primarily from respiratory (41%) and urine (27%) cultures. Only 7.5% of positive fungal cultures were from blood, although 24490 pediatric admissions prompted 72960 bacterial and fungal blood cultures, at charges of $2.52 million. Of 14592 fungal blood cultures, &lt;2% (n = 272) were positive, involving &lt;1% (n = 97) of patients. The mean rise in number of children with fungemia was significant, from 6.8 between 1991 and 1996 to 13.0 patients per year between 1997 and 2001. Fungemia was associated with a high all-cause mortality rate (46%), particularly in immunocompromised patients (57%). Organisms recovered were primarily Candida species (91%). There was a decline in C albicans and C glabrata fungemia and an increase in C parapsilosis organisms. In 84% of patients, fungal organisms were isolated from both bacterial and fungal blood cultures, and in 74%, the same organism was isolated from additional body sites.
Conclusions. Episodes of fungemia increased significantly over 11 years as compared with a moderate increase in positive fungal cultures and were associated with high all-cause mortality rates. More sensitive assays for early identification of fungal bloodstream infections are warranted.
Children With Idiopathic Short Stature Are Poor Eaters and Have Decreased Body Mass Index
Authors: Wudy Stefan A. , Hagemann Sandra , Dempfle Astrid , Ringler Gundula , Blum Werner F. , Berthold Lars D. , Alzen Gerhard , Gortner Ludwig , Hebebrand Johannes 
Published: July 2005

Objective. In children with idiopathic short stature (ISS), studies investigating body mass index (BMI) or parameters of satiety regulation are scarce, and studies analyzing eating behavior are lacking.
Methods. We recruited 214 children (123 index cases and 91 siblings) with ISS from 123 families. Affected children had to have a body height &lt;5th percentile, or, in the case of siblings, the body height of 1 child had to be &lt;5th percentile and the other &lt;15th percentile. Medical histories were recorded by using structured and standardized interviews. Eating behavior was assessed by using the Child Eating Behavior Questionnaire. Percent energy intake as fat was assessed by using the Leeds Food Frequency Questionnaire. Endocrine markers of body weight regulation (leptin, ghrelin) were determined in serum.
Results. Compared with population norms, BMI was significantly lower (mean: −0.33 standard deviation score). Furthermore, there was decreased food responsiveness (mean Child Eating Behavior Questionnaire score: 1.9; population mean: 2.4), reduced enjoyment of food (3.2 vs 3.9), emotional undereating (2.6 vs 3.0), lower desire to drink (2.0 vs 2.8), and increased fussiness over food (3.2 vs 2.9). When the sample was subdivided into the 2 groups of “good” and “poor” eaters according to the mothers' assessment of the current eating behavior, reduction in BMI as well as the behavioral characteristics already delineated in the total sample were found to be even more consistent in the subgroup of poor eaters. In the total sample of our children, as well as in both subgroups, serum leptin (adjusted for gender, BMI, and Tanner stage) was found to be moderately raised but did not differ between poor and good eaters. Total serum ghrelin was not different between poor and good eaters.
Conclusions. Our clinical, behavioral, and endocrinologic findings in patients with ISS point to an altered eating behavior that possibly contributes to their short stature.
The Epidemiology of Recurrent Abdominal Pain From 2 to 6 Years of Age: Results of a Large, Population-Based Study
Authors: Ramchandani Paul G. , Hotopf Matthew , Sandhu Bhupinder , Stein Alan ,   and the ALSPAC Study Team
Published: July 2005

Objective. Recurrent abdominal pain (RAP) is one of the most common complaints of childhood and is associated with several adverse outcomes in adulthood. Few large, population-based, longitudinal studies have been conducted. The purpose of this study was to investigate the prevalence and epidemiologic features of RAP through early childhood.Design. We report findings from a large, population-based, cohort study of childhood (the Avon Longitudinal Study of Parents And Children). The prevalence and continuity of RAP from 2 to 6 years of age were explored, with associated physical and psychological symptoms among the children and their parents.Results. In a population cohort of 13971 children, RAP was reported for 11.8% of 6-year-old children. It was less common at ages 2 years (3.8%) and 3 years (6.9%). There was a striking degree of continuity of RAP between the ages of 2 and 6 years. RAP was associated with headaches and limb pains among children and with higher rates of anxiety among both children (adjusted odds ratio: 2.12; 95% confidence interval: 1.70–2.65) and their mothers (odds ratio: 1.75; 95% confidence interval: 1.30–2.36).Conclusions. In a large, population-based, cohort study, RAP was found to be increasingly common up to the age of 6 years. Children with RAP at a young age have a high risk of RAP later in childhood. RAP is associated with other somatic pain symptoms among children and with symptoms of anxiety among children and their mothers. These findings highlight the high prevalence and continuity of RAP through early childhood and the importance of considering psychological symptoms for these children and their families.