Atypical polycystic ovary syndrome--a genetic analysis.

BACKGROUND/AIMS: Although polycystic ovary syndrome (PCOS) is a common endocrinopathy the pathogenesis is not entirely understood. Typically, high androgen levels are associated with increased virilization. We report 2 rare groups of patients with either unexpectedly high testosterone levels despite low virilization as well as patients with low testosterone levels despite high grade of virilization. One possibility for the atypical PCOS may be based on an altered androgen receptor (AR) signaling. METHODS: 6 patients and when available the parents were included in this study. Alterations of the metaphase chromosomes by GTG staining, the length of both the trinucleotide CAG- and GGC-repeats of the androgen receptor (AR) gene was determined by PCR, further the entire AR gene was sequenced and analyzed. RESULTS: The GTG banding revealed no chromosomal alterations and the range of CAG- and GGC-repeat lengths are within the normal range. Interestingly, by sequencing of the entire AR gene few genetic mutations were identified. CONCLUSION: The detected mutations do not alter the AR protein sequence but they change the codon usage towards less frequent codons that potentially may alter AR protein levels and androgen signaling. In addition to this, we postulate also other causes for manifestation of atypical PCOS, which may include AR-coregulators or epigenetic alterations. To our knowledge this is the first report of combining chromosomal analysis of PCOS patients with full sequencing of the human AR gene and linking codon usage to PCOS.

Evaluation of the prognostic meaning of C-reactive protein (CRP) in children and adolescents with classical Hodgkin's lymphoma (HL).

BACKGROUND: In adult cancer patients the negative predictive value of elevated CRP levels has been described for several malignancies. Only few studies have analyzed the prognostic role of CRP in children and adolescents with classical HL. In these studies elevated CRP levels correlate with the presence of classical risk factors and adverse outcome. PATIENTS AND METHODS: The prognostic role of CRP for patients with classical HL admitted to the GPOH-HD-2002 study was analyzed retrospectively. RESULTS: CRP levels were documented for 369 of 573 patients. Significant (p<0.05) increased median CRP levels were found in the presence of B-Symptoms (25.7 vs. 5.1 mg/l), extranodal involvement (21.5 vs. 7.5 mg/l), elevated erythrocyte sedimentation rate (ESR, 13.0 vs. 1.0 mg/l) and stage III/IV disease (15.5 vs. 5.3 mg/l). 83.9% of patients with elevated and 45.8% of patients with normal CRP had an ESR >30 mm/h. CONCLUSION: Elevated CRP levels were associated with classical risk factors of HL. CRP and ESR may reflect different biological processes. CRP was prognostic within early stage TG-1 patients treated with reduced treatment, but not within advanced stage TG-2+3.

[Smoking during pregnancy: risk for intrauterine growth retardation and persisting microsomia]. / Rauchen während der Schwangerschaft - Risiko für intrauterine Wachstumsrestriktion und bleibende Kleinwüchsigkeit.

Smoking during pregnancy is a major risk factor for intrauterine growth retardation. The aim of the Thuringian SGA - (small-for-gestational-age) - study was to evaluate the effects of maternal smoking during pregnancy on birth weight and length as well as postnatal growth dynamics and catch-up growth.Between 1992 and 2002 in all 2 447 liveborn children were assessed with birth weight (GG) <10th percentile and/or birth length (GL) <- 2.0 SDS. A questionnaire was sent to 383 parents of severe SGA children (GG and/or GL <- 2.5 SDS) to report weight and height of the children actually. 108 reports could analysed (mean age 8.0±3.4 years of life).The number of SGA babies in regard to all liveborn children decreased from 14.1% to 9.4% between 1992 and 2002. 14% of SGA babies were born preterm. The mean nicotine abuse was 2 cigarettes per day (range 0-40). 17.6% of the mothers of SGA babies were smoking, whereas in severe SGA 26.9% of smokers was recorded. There is a inverse correlation of nicotine abuse with birth weight (r=- 0.09; p<0.01) or birth length (r=- 0.08; p<0.01). Catch-up growth did not exist in 30.6% of the severe growth restricted children. The risk for short stature in later life was doubled in SGA children.Nicotine abuse during pregnancy is a risk factor for an SGA baby and could have long-lasting effects on growth dynamics during childhood with a lack of catch-up growth.

Management of oncology patients admitted to the paediatric intensive care unit of a general children's hospital - a single center analysis.

BACKGROUND: The improving prognosis of children with cancer has partially been attributed to the increasing importance of pediatric intensive care units (PICU). We analyze whether outcome of these patients on a PICU improved during the last decade and which factors may influence the outcome in our hospital. PATIENTS AND METHODS: The charts of all oncology patients admitted to the PICU between 1998 and 2009 have been reviewed retrospectively. The survival of patients admitted for life threatening complications has been correlated with basic data, organ failure and the PRISM score. The results of 2 consecutive treatment periods (1998-2003 and 2004-2009) were compared. RESULTS: 644 admissions of 226 patients were recorded. 79 admissions were performed because of potentially life threatening complications (Group A), 236 for monitoring (B) and 329 admissions for interventions (C). 62% of Group A patients and all Group B and C patients were discharged alive. Poor outcome was associated with admission >28 days after initial diagnosis, PRISM >10, organ failure >2 organs, sepsis, allogeneic stem cell transplantation, need for mechanical ventilation or for catecholamines. The PICU survival rate of Group A patients admitted between 2004 and 2009 (78%) was higher than in the period between 1998 and 2003 (48%). CONCLUSIONS: PICU provides essential services to support the pediatric oncology ward. Although children with cancer may have had benefit from advances in pediatric intensive care over the past decade, specific scoring systems for early identification of children with cancer needing PICU treatment are required. These systems might further improve PICU outcome in critical ill pediatric cancer patients.

Granulosa cell subtypes vary in response to oxidized low-density lipoprotein as regards specific lipoprotein receptors and antioxidant enzyme activity.

CONTEXT: The oxidized low-density lipoprotein (oxLDL) and its lectin-like oxLDL receptor-1 (LOX-1) are found in the follicular fluid and in granulosa cells. Lipoprotein receptors and antioxidant enzymes could differ in granulosa cell subtypes. OBJECTIVE: Our aim was to reveal cell-specific responses under oxLDL treatment. DESIGN AND SETTING: We conducted basic research at the Institute of Anatomy and the Clinic of Reproductive Medicine. PATIENTS: Women undergoing in vitro fertilization therapy participated in the study. MAIN OUTCOME MEASURES: Cultures of cytokeratin-positive/negative (CK(+)/CK(-)) granulosa cells and of cumulus cells were treated with 150 microg/ml oxLDL or native LDL under serum-free conditions for up to 36 h. Dead cells were determined by uptake of propidium iodide. LOX-1, toll-like receptor 4, and cluster of differentiation 36 (CD36) were examined in lysates by Western blots. The enzyme activities were determined in lysates and in supernatants. RESULTS: Under oxLDL treatment, predominantly CK(+) cells underwent nonapoptotic cell death. Receptors showed a cell-specific pattern of up-regulation: toll-like receptor 4 in CK(+) cells, LOX-1 in CK(-) cells, and CD36 in cumulus cells. An antioxidant ranking occurred: superoxide dismutase activity in CK(+) cells, total glutathione in CK(-) cells, and catalase activity in cumulus cells. The supernatants of oxLDL-treated CK(+) cell cultures contained more catalase activity than in controls, whereas a moderate increase was noted for glutathione peroxidase (GPx) in supernatants of CK(-) and cumulus cells. CONCLUSIONS: Catalase/GPx activity in the supernatants may be due to cell death or to secretion. Oxidative stress could be sensed by CK(+) cells and indicated by changes in catalase/GPx activity in the follicular fluid during ovarian disorders.

[Assessment of skeletal age using a new ultrasound method]. / Abschätzung des Knochenalters mit einer neuen Ultraschallmethode.

PURPOSE: Determination of skeletal development in children is important. The most used evaluation method is to study left hand X-ray based on the standards depicted by Greulich and Pyle. The aim of our study was to compare the accuracy of a new sonographically based method with the standard method. MATERIAL AND METHODS: 160 consecutive evaluated children and adolescents (77 male, 83 female) who received a X-ray of the left hand were evaluated. Ultrasound examination of the same hand was performed on the same day using the BonAge system (Sunlight Medical Ltd., Israel). This system evaluates the relationship between the velocity of the wave (speed of sound) passing thorough the distal radial and ulna epiphysis and growth, using gender- and ethnicity-based algorithms. Three experienced investigators (U1-U3) analysed the X-ray and assigned bone age scores based on the Greulich and Pyle atlas (G and P). The investigators were blinded to the calendary age (CA) of the patient and also for the BonAge result. Correlation between BonAge system results and G and P was performed using SPSS 12.0.1. RESULTS: In 152 patients BonAge measurement could be performed successfully. The correlation between the three investigators using the G and P method was between 0.977 and 0.980; correlation between the BonAge system and the investigators (U1-U3) was 0.902 and 0.920. The paired t-test showed no significant differences between the BonAge system and the three investigators and also for the comparison between U1 and U2. There were significant differences between U1 vs. U3 and U2 vs. U3 (p < 0.05). DISCUSSION: The BonAge device demonstrates the ability to produce an sufficient assessment of bone age using an ultrasound method. The results are correlated with conventional skeletal age evaluation using the G and P method. Advantages of the ultrasound device are objectivity, lack of ionizing radiation, and easy accessibility. In the case of first investigation X-ray is necessary to look for dissociated skeletal age, dysplasia, and mineralisation.

Insulin-like growth factor I correlations to changes of the hormonal status in puberty and age.

IGF-I is considered to be one of the most important growth factors during puberty. Information concerning its correlation to thyroid hormones (T3, T4), adrenal and sex steroids is limited to puberty and the elderly. The presented study included 455 subjects (among them 259 children) ranging in age from newborn to 100 years. Serum IGF-I concentrations increase from childhood to the end of puberty (2 years earlier in girls). There are close positive correlations between IGF-I concentrations and age, height and weight and between IGF-I and estradiol or testosterone concentration in girls and boys respectively, and the DHEA-S level in boys during puberty. Correlations also exist with T3, aldosterone and 17 OH-progesterone in boys and girls in the pubertal stages I-V and with T4 in stages I-IV. Compared to 20-30 year-old subjects IGF-I concentrations amounted to 59% after 60 years, 43% in men and 54% in women after 70 years and 29% after 90 years. It is suggested that increasing adrenal DHEA-S concentrations stimulate IGF-I synthesis and by means of gonadal steroidogenesis, increase the pubertal GH secretion and the further pubertal IGF-I increase. The low IGF-I concentrations in patients > 60 years reflect the more catabolic metabolism of the elderly.