bluuebunny/crossref_metadata_2025_split huggingface dataset:
Decreased soluble leptin receptor levels in women with polycystic ovary syndrome
Authors: Hahn Susanne , Haselhorst Uwe , Quadbeck Beate , Tan Susanne , Kimmig Rainer , Mann Klaus , Janssen Onno E 
Published: February 2006

Objective: Polycystic ovary syndrome (PCOS) is associated with insulin resistance and a high incidence of obesity. Leptin, the product of the ob gene, is involved in the regulation of energy balance and obesity and circulates in both free and bound forms. The soluble leptin receptor (sOB-R) is the most important leptin-binding protein, thus influencing the biologically active free leptin level.
Design: We assessed the correlation of metabolic and endocrine parameters with leptin and sOB-R levels in 122 PCOS women (aged 27 ± 5.7 years) and 81 healthy controls (aged 25 ± 4.0 years).
Methods: Leptin and sOB-R levels were measured using ELISA kits. In addition, anthropometric variables, body fat and endocrine parameters were evaluated and a glucose tolerance test performed to assess indices of insulin resistance and glucose metabolism.
Results: In PCOS patients, no correlation was found between leptin or sOB-R and parameters of hyper-androgenism. However, as expected, body mass index (BMI), body fat, waist circumference and indices of insulin resistance were significantly correlated with leptin in PCOS subjects and controls. In a subgroup analysis of lean, overweight and obese PCOS patients, significant differences were found in leptin (29.7 ± 20.7 vs 45.4 ± 25.0 vs 67.7 ± 28.8 ng/ml, P < 0.0001) and sOB-R (8.0 ± 3.4 vs 6.4 ± 2.5 vs 5.7 ± 2.3 ng/ml, P < 0.05). Compared with BMI-matched controls, lean PCOS patients had lower sOB-R levels (8.0 ± 3.4 vs 12.7 ± 4.7 ng/ml, P < 0.0001) and higher free leptin indices (4.5 ± 3.9 vs 2.8 ± 2.2, P = 0.0285).
Conclusion: Taking into account that low sOB-R levels supposedly compensate diminished leptin action, PCOS per se might cause leptin resistance.
Elevated transaminases during medical treatment of acromegaly: a review of the German pegvisomant surveillance experience and a report of a patient with histologically proven chronic mild active hepatitis
Authors: Biering H , Saller B , Bauditz J , Pirlich M , Rudolph B , Johne A , Buchfelder M , Mann K , Droste M , Schreiber I , Lochs H , Strasburger C J 
Published: February 2006

Objective: The new GH receptor antagonist pegvisomant is the most effective medical therapy to normalize IGF-I levels in patients with acromegaly. Based on currently available data pegvisomant is well tolerated; however, treatment-induced elevation of transaminases has been reported and led to the necessity for drug discontinuation in some patients in the pivotal studies. The aim of this study was to evaluate and characterize the prevalence of elevated transaminases and to describe in detail the findings in a single case who required drug discontinuation because of elevation of transaminases which emerged during treatment and who underwent liver biopsy.
Design and methods: Retrospective safety analyses were carried out on 142 patients with acromegaly receiving pegvisomant treatment in Germany between March 2003 and the end of 2004. Of these patients, 123 were documented in a post-marketing surveillance study, one case of elevated transaminases was reported spontaneously and the other patients were treated in a clinical study.
Results: Mean treatment duration with pegvisomant in the ongoing observational study at the end of 2004 was 28.3 ± 19.9 (S.D.) weeks. Twelve out of the 142 patients had elevated transaminases above three times the upper limit of normal, likely caused by biliary obstruction in five of the patients. All patients but one affected by elevated transaminases had been previously treated with somatostatin analogues. In six out of 142 (4%) of patients, pegvisomant was permanently withdrawn because of elevated transaminases. The same number of patients showed a transient increase of transaminases with either spontaneous remission without dose modification (n = 4) or no re-increase of transaminases after temporary discontinuation and re-exposure (n = 2). The liver biopsy of one patient who was permanently withdrawn showed a chronic mild hepatitis with a mixed portal inflammation including eosinophilic granulocytes.
Conclusions: Liver function tests should be regularly followed on pegvisomant treatment. Biliary complications, which may arise from restitution of normal gall bladder motility after cessation of somatostatin analogue treatment, need to be differentiated from pegvisomant-induced abnormalities. The histological pattern of the liver biopsy performed in one of the patients showed a mild chronic active hepatitis. The lack of dose dependency and rather low frequency of elevated transaminases in those cases where a biliary disorder was excluded render this reaction an idiosyncratic drug toxicity.
Fetal microchimerism in Hashimoto’s thyroiditis: a quantitative approach
Authors: Klintschar Michael , Immel Uta-Dorothee , Kehlen Astrid , Schwaiger Patrizia , Mustafa Tarek , Mannweiler Sebastian , Regauer Sigrid , Kleiber Manfred , Hoang-Vu Cuong 
Published: February 2006

Objective: Fetal microchimerism (MCH) has been implicated in the etiology of autoimmune diseases such as autoimmune thyroiditis. The goal of the study was to reliably estimate the number of fetal engrafted cells and to further investigate factors influencing the development of MCH.
Methods: Quantitative real-time PCR amplification using Y-chromosome specific (DYS14) and autosomal (β-globin) loci was performed on thyroid gland specimens. Furthermore, we compared the distribution of ABO and rhesus systems in mothers with and without blood MCH in relation to the blood groups of the children.
Results: MCH was detected in eight of 21 Hashimoto patients in a frequency range of 15 to 4900 male cells per 100 000 total cells (median 97 cells), but in none of 17 healthy thyroid glands. In a third group, consisting of 18 nodular goiters, only one sample was positive (182 male cells/100 000 total cells). No woman who had not had a prior pregnancy with a male fetus showed MCH. Mothers both with and without MCH showed the same rate of mother/child incompatibilities for the ABO and rhesus systems.
Conclusions: The percentage of microchimeric cells varies to a great extent in Hashimoto’s thyroiditis, and this phenomenon can occur in nodular goiter in rare instances, but it appears to be absent from normal thyroid glands. Nevertheless, the biological significance of MCH remains unclear. Moreover, we have concluded that the tested blood group systems (as opposed to their role in graft vs host disease after transplantations) have no effect on fetal MCH.
Leukemia inhibitory factor reduces body fat mass in ovariectomized mice
Authors: Jansson John-Olov , Movérare-Skrtic Sofia , Berndtsson Anna , Wernstedt Ingrid , Carlsten Hans , Ohlsson Claes 
Published: February 2006

Objective: Ovariectomized (OVX) mice are known to gain body fat while exposure to estrogens decreases fat mass. We have previously shown that estrogen replacement therapy enhances the expression of receptors for the cytokine, leukemia inhibitory factor (LIF). LIF and other cytokines acting via the gp130 signal transducing receptor have been reported to decrease obesity. In the present study, we investigated whether LIF treatment can reduce obesity in OVX mice.
Design: Eight-week-old female C57Bl/6 mice were OVX or sham-operated. The mice were treated with LIF, 30 μg/kg or PBS via daily i.p. injections for 15 days (n = 9–10).
Methods: Dual X-ray absorptiometry and computerized tomography.
Results: We found that LIF treatment of OVX mice caused a significant reduction in the weight of white fat depots (P = 0.017) and serum leptin levels (P = 0.011). LIF also caused a significant decrease in brown fat mass (P = 0.036). Treatment with LIF decreased thymus weight but did not affect crown-rump length, femur length, trabecular bone mineral density or the weight of several non-fat organs including the uterus.
Conclusion: The cytokine, LIF, decreases body fat mass in OVX mice, suggesting that estrogen signaling is not required for this effect.
Association between serum ferritin and the insulin resistance syndrome in a representative population
Authors: Wrede C E , Buettner R , Bollheimer L C , Schölmerich J , Palitzsch K-D , Hellerbrand C 
Published: February 2006

Objective: Unexplained hepatic iron overload with increased serum ferritin (SF) values has been associated with the insulin resistance syndrome (IRS), defined by the presence of one or more of the following criteria: increased body mass index (BMI), diabetes, hyperlipidemia or hypertension. However, as yet the association between IRS and SF in a representative population has not been investigated.
Methods: The study subjects participated in a nationwide epidemiological survey on metabolic disorders in the adult German population. The 1200 probands included in this study are representative of the German population. To eliminate major causes of secondary iron overload, 114 (9.5%) subjects with excessive alcohol consumption and 16 (1.5%) subjects with serological evidence for hepatitis B or C were excluded. For all remaining 1070 probands, complete clinical data of SF, HbA1c, known diabetes, BMI, cholesterol, high-density lipoprotein-cholesterol and blood pressure were available.
Results: SF values were significantly increased in men and women with high BMI (> 25 kg/m2), increased cholesterol (> 200 mg/dl), and increased systolic (> 160 mmHg) blood pressure, in women with diabetes, and in men with increased diastolic (> 95 mmHg) blood pressure. Furthermore, there was a significant correlation between the number of IRS criteria and SF.
Conclusions: This study shows a significant correlation between SF and the presence of IRS criteria in a large representative population. Interestingly, the severity of the IRS seems to be associated with increased SF levels suggesting a causal connection. Further studies are required to investigate the pathophysiological mechanism and consequences of increased SF levels in patients with IRS.
Plasma adiponectin concentration and tumor necrosis factor-α system activity in lean non-diabetic offspring of type 2 diabetic subjects
Authors: Kowalska Irina , Strączkowski Marek , Nikolajuk Agnieszka , Krukowska Agnieszka , Kinalska Ida , Górska Maria 
Published: February 2006

Objective: There is growing evidence that adiponectin function is related to the pathogenesis of insulin resistance. Insulin resistance might be present even in lean subjects with a strong family history of type 2 diabetes. The aim of the study was to look for adiponectin’s role in the pathogenesis of insulin resistance in offspring of type 2 diabetic patients, and its relation to the activity of the tumor necrosis factor (TNF)-α system.
Research design and methods: The study was carried out in 23 lean offspring of type 2 diabetic subjects and in 23 controls matched for age, sex and body mass index. The oral glucose tolerance test for glucose and insulin estimations and hyperinsulinemic, euglycemic clamp studies were performed in all patients. The plasma concentration of adiponectin, TNF-α, soluble TNF receptors 1 and 2 (sTNFR1, sTNFR2), HbA1c, total cholesterol, high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein-cholesterol and triglycerides were estimated.
Results: The insulin sensitivity index, normalized for fat-free mass (Mffm) and adiponectin concentrations were markedly decreased in offspring of type 2 diabetic subjects compared with the control group (P = 0.0046 and P = 0.00 058 respectively). TNF-α and sTNFR1 concentrations did not differ between the studied groups; however the concentration of sTNFR2 was markedly increased in the offspring of type 2 diabetic patients (P = 0.0002). Adiponectin concentration was positively correlated to the insulin sensitivity index (r = 0.34; P = 0.020) and to HDL-cholesterol (r = 0.29, P = 0.047) and was inversely related to sTNFR2 (r = −0.33, P = 0.027).
Conclusions: The obtained results suggest that adiponectin could play a role in the pathogenesis of insulin resistance in lean offspring of type 2 diabetic subjects.
Prepubertal gynecomastia in Peutz-Jeghers syndrome: incomplete penetrance in a familial case and management with an aromatase inhibitor
Authors: Lefevre Hervé , Bouvattier Claire , Lahlou Najiba , Adamsbaum Catherine , Bougnères Pierre , Carel Jean-Claude 
Published: February 2006

Background: Peutz-Jeghers syndrome (PJS) is a rare autosomal-dominant disorder characterized by multiple gastrointestinal hamartomatous polyps, mucocutaneous pigmentation and increased predisposition to various neoplasms. Endocrine manifestations in PJS include gynecomastia due to calcified Sertoli cell testicular tumors usually referred to as large-cell calcifying Sertoli cell tumors (LSCT).
Objective: To evaluate the value of endocrine markers and aromatase inhibitor treatment in children with PJS and LSCT.
Design and setting: Familial cases, followed in a tertiary care center.
Patients: Two male siblings aged 7 and 9 years with PJS and LSCT.
Intervention: Third generation aromatase inhibitor (anastrozole) in one of the patients.
Main outcome measures: Longitudinal measurements of sex-steroids, gonadotropins, Sertoli cell markers and auxological evaluation.
Results: The two male siblings with PJS had similar bilateral multifocal testicular calcifications and biochemical evidence of Sertoli cell dysfunction manifested by elevated plasma inhibin-α levels. Only one sibling had gynecomastia. Estradiol levels were normal in both. During treatment with anastrozole, estradiol levels, growth and skeletal maturation, as well as Sertoli cell markers (inhibin B, inhibin-α and anti-Mullerian hormone) decreased.
Conclusions: Inhibin-α may be considered as a marker for LSCT in children with PJS, pointing to a specific defect in inhibin regulation in this condition. Moreover, the decrease in Sertoli cell markers during aromatase inhibitor treatment suggests that increased estrogen production is a primary event regulating downstream production of Sertoli cell peptides. Anastrozole is efficient in controlling the clinical features of the disease and should be proposed as an alternative to bilateral orchidectomy, which is often performed in this condition.
The direct effects of the angiotensin-converting enzyme inhibitors, zofenoprilat and enalaprilat, on isolated human pancreatic islets
Authors: Lupi Roberto , Guerra Silvia Del , Bugliani Marco , Boggi Ugo , Mosca Franco , Torri Scilla , Prato Stefano Del , Marchetti Piero 
Published: February 2006

Objective: Data from prospective studies suggest a significant reduction in the risk of new diabetes from drug therapies containing angiotensin-converting enzyme (ACE) inhibitors. Since the renin–angiotensin system (RAS) has been found locally in several tissues and cells, including pancreatic islets, we hypothesized that the positive metabolic effects of ACE inhibitors may be due to a beneficial action of these compounds on insulin-secreting β-cells.
Design and methods: Isolated human pancreatic islets were studied after 24 h of incubation with 22.2 mmol/l glucose, with or without the presence in the incubation medium of 0.5–6.0 mmol/l zofenoprilat or enalaprilat, ACE inhibitor drugs which differ by the presence of a sulphydryl or a carboxyl group in their structural formula. Functional and molecular studies were then performed to assess insulin secretion, redox balance, mRNA and protein expression.
Results: Angiotensinogen, ACE and angiotensin type 1 receptor mRNA expression increased in islets cultured in high glucose; this was similarly prevented by the presence of either ACE inhibitor. As expected, preculture of human islets in high glucose determined a marked reduction in insulin secretion which was associated with enhanced oxidative stress, as shown by increased nitrotyrosine concentrations, and enhanced expression of protein kinase C β and NADPH oxidase. The presence of either of the ACE inhibitors counteracted several of the deleterious effects of high glucose exposure, including reduction of insulin secretion and increased oxidative stress; zofenoprilat showed significantly more marked effects.
Conclusions: These results showed that: (a) RAS molecules are present in human islets and their expression is sensitive to glucose concentration, (b) ACE inhibitors, and in particular zofenoprilat, protect human islets from glucotoxicity and (c) the effects of ACE inhibition are associated with decreased oxidative stress. Together, these findings provide evidence that the possible beneficial effects of ACE inhibitors in human diabetes are due, at least in part, to a protective action on pancreatic β-cells.
Treatment of tall stature in boys with somatostatin analogue 201–995: effect on final height
Authors: Noordam C , van Daalen S , Otten BJ 
Published: February 2006

Background: An optimal treatment for tall stature in boys in terms of efficacy and safety is not available. Treatment with somatostatin analogue 201–995 (SMS) has been tried with positive short-term results.
Methods: We evaluated the effect of SMS treatment on reducing adult height. Over 2 years, 16 boys presenting to our university hospital with tall stature (constitutional tall stature (n = 13), Marfan syndrome (n = 2) and tethered spinal cord (n = 1)) with a predicted final height above 197 cm were included in the study and prospectively followed until final height was reached. As one boy was lost to follow-up we have reported on 15 boys. Treatment with SMS as a single subcutaneous dose was started and continued until final height was reached. In eight boys androgens were given to induce puberty after the start of SMS and five boys were on treatment with androgens prior to SMS treatment. Effect on reduction of final height prediction, calculated with the index of potential height based on the bone age of Greulich and Pyle, was the main outcome measure. Standard anthropometric assessments were performed a year before and every 3 months during treatment. Bone age was assessed by the method of Greulich and Pyle at the start and after 6 and 12 months.
Results: Mean reduction in final height prediction (predicted adult height minus achieved adult height) was −0.1 cm (range −6.4 to +5.7). In three boys, asymptomatic microlithiasis of the gall bladder was diagnosed.
Conclusions: We have concluded that, in spite of encouraging short-term results, long-term treatment with SMS does not reduce final height in a manner sufficient to justify SMS treatment in tall stature.
Celiac disease in North Italian patients with autoimmune Addison’s disease
Authors: Betterle Corrado , Lazzarotto Francesca , Spadaccino Aglaura Cinzia , Basso Daniela , Plebani Mario , Pedini Beniamino , Chiarelli Silvia , Albergoni Mariapaola 
Published: February 2006

Objective: Patients with autoimmune Addison’s disease (AAD) are prone to develop other autoimmune manifestations. An increased prevalence of celiac disease (CD) has recently been demonstrated in Northern European patients with AAD. IgA deficiency is the most frequent type of immunodeficiency among humans and is present in about one in every 600 individuals in the population. IgA deficiency is frequent in patients with other autoimmune diseases, but data concerning AAD are still unavailable.
Design: The aim was to define the prevalence of CD and of IgA deficiency in a group of Italian patients with AAD.
Methods: One hundred and nine patients with AAD were enrolled and examined for tissue transglutaminase autoantibodies of the IgA class, circulating levels of IgA and adrenal cortex antibodies.
Results: Two (1.8%) of the patients were affected by already diagnosed CD and were already on a gluten-free diet. Out of the remaining 107 patients, four (3.7%) were found to be positive for IgA antibodies to human tissue transglutaminase. Three of the four patients who were positive for tissue transglutaminase autoantibodies agreed to undergo endoscopy and duodenal biopsies and, in one, a latent form of CD was identified. The clinical, silent or latent form of CD was present in six out of 109 (5.4%). This prevalence was significantly higher (P = 0.0001) than that reported for the Northern Italian population which was equal to 0.063%. Specifically, CD was present in 12.5% of the autoimmune polyglandular syndrome (APS) type 1 cases, in four out of 60 (6.7%) of the APS type 2 cases and in one out of 40 (2.5%) of the isolated AAD cases. IgA deficiency was present in two out of 109 patients (1.8%), all of whom had normal IgG anti-gliadin. Autoantibodies to the adrenal cortex were detected in 81 out of 109 patients (74.3%).
Conclusions: In patients with AAD there is a high prevalence of both CD and IgA deficiency. Consequently, it is important to screen for CD with tissue transglutaminase autoantibodies of the IgA class and for IgA levels.
Systemic monocyte chemoattractant protein-1 concentrations are independent of type 2 diabetes or parameters of obesity: results from the Cooperative Health Research in the Region of Augsburg Survey S4 (KORA S4)
Authors: Herder Christian , Müller-Scholze Sylvia , Rating Philipp , Koenig Wolfgang , Thorand Barbara , Haastert Burkhard , Holle Rolf , Illig Thomas , Rathmann Wolfgang , Seissler Jochen , Wichmann H-Erich , Kolb Hubert 
Published: February 2006

Objective: Data on the relevance of monocyte chemoattractant protein (MCP)-1 in the pathophysiology of type 2 diabetes (T2D) and obesity are inconsistent. Since MCP-1 is produced by adipocytes and has been postulated to be involved in macrophage infiltration into adipose tissue, we wanted to test whether serum MCP-1 levels were correlated with T2D or obesity.
Design and methods: Out of 1653 individuals aged 55 to 74 years participating in the population-based KORA Survey S4 (KORA/Cooperative Health Research in the Region of Augsburg) in Southern Germany, 236 patients with T2D, 242 subjects with impaired glucose tolerance and 244 normoglycaemic controls matched for age and sex were analysed for circulating MCP-1 concentrations.
Results: MCP-1 serum concentrations were not associated with impaired glucose tolerance, type 2 diabetes or several parameters of obesity. Moreover, systemic MCP-1 levels were not significantly correlated with all but one (fasting triglycerides) of the biochemical markers tested.
Conclusions: Our data indicate that MCP-1 levels are not associated with T2D and that the contribution of fat mass to systemic MCP-1 protein might be low, suggesting that the possible local pathogenic role of MCP-1 may not be reflected by increased systemic levels of MCP-1.