Gamma-glutamyl-transferase is associated with incident hip fractures in women and men ≥ 50 years: a large population-based cohort study.

The association of serum gamma-glutamyl-transferase (GGT) with hip fracture risk has not been examined in women and men ≥ 50 years. We show that elevated GGT was associated with increased hip fracture risk, particularly in men. GGT could be a candidate serum marker of long-term hip fracture risk in the elderly. INTRODUCTION: We herein examined a possible relation between serum levels of GGT and hip fracture risk in women and men aged ≥ 50 years, which has not been investigated before. METHODS: In this population-based prospective cohort study, approximately 41,000 women and nearly 33,000 men ≥ 50 years participating in a medical prevention program 1985-2005 in western Austria were followed up for the occurrence of osteoporotic hip fractures during 2003-2013. ICD-10 based discharge diagnoses for hip fracture included S72.0, S72.1, and S72.2 available from all regional hospitals. GGT-related hip fracture risk was ascertained at each participant´s first and last examination during the prevention program. In a subset of 5445 participants, alcohol consumption could be included as a covariate. RESULTS: In men, hip fracture risk rose significantly by 75% and 86% for every tenfold increase of GGT measured at the first and last examination, respectively, and in women, hip fracture risk rose by 22% from the last examination. Elevated GGT (≥ 36 U/l in women, ≥ 56 U/l in men) at the first examination was associated with increased hip fracture risk only in men (HR 1.51, 95% CI 1.25-1.82), and at the last examination in both women (HR 1.14, 95% CI 1.02-1.28) and men (HR 1.61, 95% CI 1.33-1.95). Alcohol consumption had no significant influence on GGT-mediated hip fracture risk in women and men. CONCLUSIONS: Our findings identified an association of elevated GGT and hip fracture in women and men ≥ 50 years and suggest GGT as a candidate serum marker of long-term hip fracture risk in an elderly population.

Vaginal prolapse surgery with transvaginal mesh: results of the Austrian registry.

INTRODUCTION AND HYPOTHESIS: Several mesh repair systems for pelvic organ prolapse (POP) were introduced into clinical practice with limited data on safety, complications or success rates, and impact on sexual function. The Austrian Urogynecology Working Group initiated a registry to assess the use of transvaginal mesh devices for POP repair. We looked at perioperative data, as well as outcomes at 3 and 12 months. METHODS: Between 2006 and 2010 a total of 20 gynecology departments in Austria participated in the Transvaginal Mesh Registry. Case report forms were completed to gather data on operations, the postoperative course, and results at 3 and 12 months. RESULTS: A total of 726 transvaginal procedures with 10 different transvaginal kits were registered. Intra- and perioperative complications were reported in 6.8%. The most common complication was increased intraoperative bleeding (2.2%). Bladder and bowel perforation occurred in 6 (0.8%) and 2 (0.3%) cases. Mesh exposure was seen in 11% at 3 and in 12% at 12 months. 24 (10%) previously asymptomatic patients developed bowel symptoms by 1 year. De novo bladder symptoms were reported in 39 (10%) at 3 and in 26 (11%) at 12 months. Dyspareunia was reported by 7% and 10% of 265 and 181 sexually active patients at 3 and 12 months postoperatively respectively. CONCLUSIONS: The 6.8% rate of intra- and perioperative complications is in line with previous reports. Visceral injury was rare. The 12% rate of mesh exposure is consistent with previous series.

Genetic disorders in premature ovarian failure.

This review presents the genetic disorders associated with premature ovarian failure (POF), obtained by Medline, the Cochrane Library and hand searches of pertinent references of English literature on POF and genetic determinants cited between the year 1966 and February 2002. X monosomy or X deletions and translocations are known to be responsible for POF. Turner's syndrome, as a phenotype associated with complete or partial monosomy X, is linked to ovarian failure. Among heterozygous carriers of the fragile X mutation, POF was noted as an unexpected phenotype in the early 1990s. Autosomal disorders such as mutations of the phosphomannomutase 2 (PMM2) gene, the galactose-1-phosphate uridyltransferase (GALT) gene, the FSH receptor (FSHR) gene, chromosome 3q containing the Blepharophimosis gene and the autoimmune regulator (AIRE) gene, responsible for polyendocrinopathy-candidiasis-ectodermal dystrophy, have been identified in patients with POF. In conclusion, the relationship between genetic disorders and POF is clearly demonstrated in this review. Therefore, in the case of families affected by POF a thorough screening, including cytogenetic analysis, should be performed.

Novel MUC1 splice variants are expressed in cervical carcinoma.

OBJECTIVES: The MUC1 antigen can be used to identify epithelial cells from the background of hemopoietic cells. The present investigation describes patterns of overexpression of two novel MUC1 splice variants in human cervical carcinoma cell lines. METHODS: RT-PCR was carried out to determine MUC1 splice variants in the cervical cancer cell lines C-4 II, C-33A, DoTc 2 4510, C-4 I, SiHa, HT3, Hs 636 T (C4-I), and HeLa. RESULTS: The novel MUC1 splice variant D was expressed in all cell lines and the novel MUC1 splice variant C was expressed in all cell lines but C-33A. Variants A and B were expressed in all (variant A) and all but one (variant B) cell line. MUC1/REP was expressed in all cell lines and MUC1/SEC was positive in all but two cell lines (C-33 A, DoTc 2 4510). All but one cell line (C-33A) expressed MUC1/X and MUC1/Y, and two cell lines (C-33 A, DoTc 2 4510) did not express MUC1/Z, respectively. MUC1 variants A, D, and REP could be demonstrated consistently among all eight cervical carcinoma cell lines we have examined. CONCLUSIONS: The present study describes the feasibility of detecting a large number of MUC1 variants, including MUC1 variants C and D which are described for cervical carcinoma cells for the first time. Further studies will examine the presence of MUC1 splice variants' expression in human cervical carcinoma tissue.

Concentration of vascular endothelial growth factor (VEGF) in the serum of patients with malignant bone tumors.

BACKGROUND: Vascular endothelial growth factor (VEGF) is recognized as an important stimulator of angiogenesis. Formation of new blood vessels by angiogenic factors occurs in many biological processes, both physiological and pathological, among others in growth of primary solid malignant tumors and metastasis. This implies that the inhibition of angiogenic factors like VEGF would result in a suppression of tumor growth and metastasis formation. The aim of the present study was to compare preoperative serum VEGF levels of patients having malignant bone tumors with healthy controls to identify serum VEGF levels as a tumor marker. PROCEDURE: Blood sera from patients with high-grade osteosarcoma (n = 17), chondrosarcoma (n = 4) and Ewing sarcoma (n = 6) were taken at the time of diagnosis before biopsy and compared with sera from 129 healthy persons. To measure VEGF levels in serum, a commercially available ELISA was used (Quantikine Human VEGF Immunoassay; R&D Systems). RESULTS: The observed geometric mean VEGF levels and 95% confidence intervals are 232.0 pg ml(-1) (168.9-318.5) for patients with high-grade osteosarcoma, 325.5 pg ml(-1) (169.3-625.8) for patients with chondrosarcoma, 484.3 pg ml(-1) (284.0-826.0) for patients with Ewing sarcoma, as compared to 216.2 pg ml(-1) (192.8-242.5) for healthy individuals. CONCLUSIONS: While the sample means for the three groups of sarcoma patients were higher than the respective mean for the healthy controls, only the mean for the group with Ewing sarcoma is statistically significantly higher than the mean for the healthy controls. Despite the significant difference, VEGF levels are not suitable as a marker for Ewing sarcoma.

Umbilical venous leptin concentration and gender in newborns.

OBJECTIVE: To investigate the relationship between umbilical venous leptin concentration and gender in 20 pairs of newborns matched 1:1 for birth weight and gestational age at sampling. MATERIALS: Blood samples were obtained from 40 women at delivery, identified as having an uncomplicated pregnancy. Umbilical venous blood samples were obtained from their newborns (20 males and 20 females) at birth. Specimens were analyzed using a human leptin 125-I radioimmunoassay. RESULTS: Fetal leptin correlated positively with birth weight (rs = 0.541; P < .001). Umbilical venous leptin concentrations in female newborns (median: 10.7 ng/mL, range: 3.5-34.4 ng/mL) were significantly higher (P = .028) than in male newborns (median: 7.7 ng/mL, range: 2.0-19.3 ng/mL). There was no significant correlation between maternal and fetal leptin concentrations. Multiple logistic regression analysis revealed birth weight and gender to be independent factors influencing fetal cord leptin. CONCLUSION: Our results suggest that in the fetus, as in children and adults, gender and weight are the major determinants of circulating leptin levels.

Decreased maternal serum leptin in pregnancies complicated by preeclampsia.

OBJECTIVE: To determine whether circulating levels of leptin differed between women with preeclampsia and women who had an uncomplicated pregnancy. METHODS: Maternal and umbilical venous plasma leptin concentrations obtained at delivery were compared in 36 pairs of women with either preeclampsia or normal pregnancy, matched 1:1 for prepregnancy body mass index and fetal gestational age at delivery. RESULTS: Prepregnancy body mass index was 21.1 +/- 2.1 kg/m2 in either study group (range 17.6-25.3 kg/m2 and 17.7-25.3 kg/m2 in the normal and preeclamptic group, respectively). Mean fetal gestational age at delivery was 40.1 +/- 1.3 weeks and 40.1 +/- 1.2 weeks in the normal and preeclamptic group, respectively. Median leptin concentrations were significantly lower (P <.0001) in women with preeclampsia (8.3 ng/mL, range 3.5-20.0 ng/mL) than in normal pregnant women (20.2 ng/mL, range 6.0-63.7 ng/mL). Median umbilical venous leptin was not significantly different between groups (preeclampsia 11.8 ng/mL, range 2.0-37.2 ng/mL; normal 7.6 ng/mL, range 1.6-24.3 ng/mL; P = .377). Umbilical venous leptin levels correlated positively with birth weight in both groups (preeclampsia rho = 0.501, P = .002; normal rho = 0.517, P = .001), whereas no correlations were found between maternal and fetal hormone concentrations. Maternal leptin concentrations did not correlate with birth weight. CONCLUSION: Our data suggest that the correlation between umbilical venous leptin concentration and birth weight is independent of the presence of preeclampsia. Given the inconsistency in literature concerning circulating leptin levels in preeclampsia, further studies should investigate the regulatory systems of leptin in preeclampsia.

Maternal serum leptin concentrations do not correlate with cord blood leptin concentrations in normal pregnancy.

OBJECTIVE: To determine whether there is a difference in maternal leptin concentration and cord blood concentration, consistent with the hypothesis of a noncommunicating, two-compartement model of fetoplacental leptin regulation. METHODS: Blood samples were collected from 139 women, identified as having an uncomplicated pregnancy, from an antecubital vein at delivery. Cord blood samples were taken from the umbilical vein. Leptin was measured by radioimmunoassay, and its relationship to fetal and maternal anthropometrics was assessed by Spearman correlation. Differences in maternal and cord blood leptin levels between male and female infants were tested with the Mann-Whitney Utest. Maternal and cord blood leptin were compared by the Wilcoxon signed rank test. The outcome measures were maternal and cord blood leptin at delivery, fetal birth weight, length, weight/length ratio, and ponderal index, maternal prepregnancy body mass index, pregnancy weight gain, relative weight gain, and body mass index at delivery. RESULTS: No correlations were found between maternal and cord blood leptin concentrations. Fetal leptin level correlated with birth weight (rho = 0.665; P <.0001), length (rho = 0.490; P <.0001), ponderal index (rho = 0.260; P =.002), and weight/length ratio (rho = 0.625; P <.0001). Median leptin concentrations were higher in female (9.3 ng/mL, range 1.5-34.4 ng/mL) than in male (8.2 ng/mL, range 1.6-38.3 ng/mL) neonates, but this difference was statistically not significant. Logistic regression analysis showed a significant influence on umbilical venous leptin concentration for birth weight (P <.0001) but not for gender. Maternal leptin concentrations were significantly higher than cord leptin concentrations (P <.0005 for the male and female neonates and the entire group). CONCLUSION: There was no correlation between maternal and cord leptin, which supports the hypothesis of a noncommunicating, two-compartment model of fetoplacental leptin regulation.

Impact of maternal anthropometry and smoking on neonatal birth weight.

The purpose of this study was to determine the effect of maternal pre-pregnancy body mass index (BMI) and maternal smoking habits on neonatal birth weight. We reviewed 10,240 normal singleton term pregnancies between 1985 and 1995 at the University Department of Obstetrics and Gynecology, Vienna. Birth weights of infants of overweight smokers were greater than those of smokers in general and similar to birth weights of nonsmokers, but smoking did have a fetal growth-retarding effect in overweight smoking mothers. Infants of underweight mothers who increased their daily cigarette consumption during pregnancy had significantly lowest birth weight. Our results suggest that the negative effects of smoking during pregnancy cannot be mitigated by a higher pre-pregnancy BMI and/or an improved weight gain during pregnancy. Especially the infants of underweight mothers benefit from their mothers' decision to cease smoking.

Impact of hysteroscopy on disease-free survival in clinically stage I endometrial cancer patients.

Recent data strongly suggest tumor cell dissemination of endometrial carcinoma cells in the course of fluid hysteroscopy. In patients who had endometrial cancer which was (except for peritoneal cytology) confined to the uterus, the disease-free survival (DFS) of 135 patients who underwent hysteroscopy prior to staging laparotomy was compared with the DFS of 127 patients without hysteroscopy. After a median follow-up of 23 months, 10 patients experienced tumor recurrence. Although there was a trend towards a higher incidence of positive peritoneal cytology at laparotomy in patients who underwent hysteroscopy, this difference did not achieve statistical significance (P = 0.47). For 5 years, the DFS was 92.4% in patients with hysteroscopy and 84.7% in patients without hysteroscopy before laparotomy (log-rank, P = 0.782). Our data therefore suggest a similar short-term DFS in endometrial cancer patients with and without hysteroscopy prior to laparotomy.

Serum leptin concentration in cord blood: relationship to birth weight and gender in pregnancies complicated by pre-eclampsia.

The aim of the study was to investigate cord blood leptin concentrations and their relationship to birth weight and gender in term pregnancies complicated by pre-eclampsia. Cord blood samples were obtained from 52 women, identified as having pre-eclampsia, and their newborns (31 males and 21 females) immediately after birth. Specimens were analyzed using a human leptin 125I radioimmunoassay. The relationship between leptin and anthropometrics was assessed by Spearman correlation. Differences in cord blood leptin levels between male and female infants were tested with the Mann-Whitney U test. The correlation between leptin and gender was computed using the product-moment-biseral correlation analysis for continuous and dichotomous variables. The multiple logistic regression analysis examined influences of sex, birth length, birth weight, birth weight/birth length ratio, ponderal index and maternal leptin as covariates on the fetal cord leptin level. Fetal leptin correlated positively with birth weight, length and weight/length ratio, in the total group and in the male subgroup and additionally with ponderal index in the female subgroup. Cord blood leptin concentrations in female newborns were significantly higher than in male newborns (p = 0.015), and concentrations correlated with gender (r = -0.315; p = 0.023). Multiple logistic regression analysis revealed four potential independent factors influencing fetal cord leptin: gender, birth weight, birth weight/birth length ratio and maternal leptin. In conclusion, cord leptin concentrations in pregnancies complicated by pre-eclampsia correlate positively with birth weight and gender. Leptin concentrations in female newborns are higher compared to male newborns.

[Angiogenesis in gynecology and obstetrics]. / Angiogenese in Gynäkologie und Geburtshilfe.

In current scientific discussion, increasing importance is being given to the clinical significance of the new formation of vessels (angiogenesis) in the course of physiological, inflammatory and neoplastic processes. Angiogenesis is best studied in the growth of malignant tumors, since cancer may be regarded as the most important angiogenesis-dependent disease in terms of social and economic aspects. The significance of angiogenesis in gynecological oncology is as follows: 1) Intratumoral vessel density is an indicator for the emergence and growth of malignant tumours and their precursor lesions, 2) intratumoral vessel density is an independent prognostic factor for solid malignancies and 3) the inhibition of tumor angiogenesis by means of anti-angiogenetic substances causes tumor growth to be suppressed. Angiogenesis also plays an important role in the regulation of the female menstrual cycle. Proliferation of the endometrium and the formation of the corpus luteum in the second half of the menstrual cycle are examples of angiogenesis in the physiological field. The function of angiogenetic factors in the emergence of endometriosis and in female and male infertility are currently under study. In obstetrics, the new formation of blood vessels is significant for the implantation of impregnated blastocysts and for the development and growth of the placenta. Preeclempsia (gestational toxicosis), for instance, is a typical pregnancy-related disease whose pathophysiological mechanism is attributed to a disturbed development and function of small placental vessels. The present paper is an overview of current knowledge and current approaches of research concerning angiogenesis in the field of gynecology and obstetrics. The paper is focused on the clinical significance of angiogenesis.

Prognostic significance of tumor angiogenesis in epithelial ovarian cancer.

Since angiogenesis is considered essential for tumor growth and the development of metastasis, we assessed the correlation of microvessel density (MVD) with overall survival in patients with epithelial ovarian cancer. Histologic slides were immunostained for CD34-antigen. MVD was determined within each tumor by enumeration under a light microscope at 200x magnification and an examination area of 0.25 mm2. The Cox proportional-hazards model was used for multivariate analysis. In 63 patients with epithelial ovarian cancer the 5-year survival rate (OS-%) was as follows: 55.0% (+/-12.5) in 18 patients whose tumors had an MVD < 10/field, and 23.6% (+/-6.7) in 45 patients whose tumors had an MVD(10/field (log-rank P = 0.038). MVD showed a significant influence on survival in univariate analysis, but failed to attain a significant value after adjustment for established prognostic parameters such as patients' age at diagnosis, stage of disease, and histologic grading. High MVD was significantly associated with advanced patients' age at diagnosis. This and a considerable heterogenity in the vascular architecture of ovarian carcinoma tissue might be the reasons why MVD did not reveal prognostic significance in multivariate analysis. In contrast to a variety of solid neoplasms, MVD does not seem to be a useful predictor of survival in patients with epithelial ovarian cancer.

Concentration of vascular endothelial growth factor (VEGF) in the serum of patients with suspected ovarian cancer.

As a promoter of angiogenesis, vascular endothelial growth factor (VEGF) is believed to play a pivotal role in tumour growth and metastasis. The aim of this study was to determine the value of preoperative serum VEGF levels in the early diagnosis of ovarian cancer and in the differential diagnosis of adnexal masses. We examined preoperative serum VEGF levels in healthy women (n = 131), patients with benign ovarian cysts (n = 81) and in ovarian cancer patients (n = 44) by using an ELISA (R&D Systems, Minneapolis, MN, USA). A logistic regression model was carried out to determine the influence of VEGF and CA 125 on the probability of malignancy. VEGF revealed a significant influence on the odds of presenting with malignancy vs healthy women (P = 0.001). At 363.7 pg ml(-1), VEGF achieved a sensitivity of 54% and a specificity of 77%. With respect to the differentiation between benign cysts and ovarian cancer, CA 125 (P < 0.0001) but not VEGF (P = 0.229) predicts the presence of malignancy in a multivariate model. In conclusion, VEGF does not appear to be a useful tool in the early diagnosis of ovarian cancer or for indicating the absence or presence of malignancy in patients with an adnexal mass.