Age intrinsic loss of telomere protection via TRF1 reduction in endothelial cells.

Aging is a major factor predisposing for multiple diseases. Telomeres at the ends of chromosomes protect the integrity of chromosomal DNA. A specialized six-protein complex termed shelterin protects the telomere from unwanted interaction with DNA damage pathways. The aim of our study was to evaluate the integrity of telomeres and the stability of telomere protection during aging in endothelial cells (EC). We describe that aging EC can be characterized by an increased cell size (40%, p=0.02) and increased expression of PAI 1 (4 fold, p=0.02), MCP1 (10 fold, p=0.001) and GMCSF (15 fold, p=0.004). Telomeric state in aging cells is defined by an increased telomere oxidation (27%, p=0.01), reduced telomere length (62%, p=0.02), and increased DNA damage foci formation (5% in young EC versus 16% in aged EC, p=0.003). This telomeric dysfunction is accompanied by a reduction in the shelterin component TRF1 (33% mRNA, p=0.001; 24% protein, p=0.007). Overexpression of TRF1 in aging EC reduced telomere-associated DNA damage foci to 5% (p=0.02) and reduced expression levels of MCP1 (18% reduction, p=0.008). Aged EC have increased telomere damage and an intrinsic loss of telomere protection. Reestablishing telomere integrity could therefore be a target for rejuvenating endothelial cell function.

Lumbar neuraxial anatomical changes throughout pregnancy: a longitudinal study using serial ultrasound scans.

This observational study was designed to investigate the anatomical changes of the lumbar spine over the course of pregnancy using serial ultrasound scans. We performed paramedian scans on 58 women at the L2-3, L3-4 and L4-5 levels; these were done at four periods of 11+0-13+6, 19+0-23+0, 28+0-32+0 and 38+0-40+0 weeks gestation. At each intervertebral level, the length of the interlaminar space, length of the visible intervertebral posterior dura and depth of the posterior dura mater from the skin were measured. The length of the interlaminar space and length of the visible intervertebral posterior dura mater were longer, and the depth of the posterior dura mater was shallower, with ascending spinal interspace. The depth of the posterior dura mater increased during pregnancy, although it plateaued between the third and fourth measurement periods. The other spinal measurements were not affected by gestation. These findings indicate that the L2-3 level is the most appropriate puncture site for epidural anaesthesia in pregnant women. Our results ought to be embraced as a departure point towards developing neuraxial insertion techniques guided or aided by ultrasound.

Sequential cervical length screening in pregnancies after loop excision of the transformation zone conisation: a retrospective analysis.

OBJECTIVE: To review our experience with a screening programme that included four sequential cervical length (CL) measurements from 16 to 22( ) weeks of gestation. DESIGN: Historical cohort study. SETTING: Tertiary-care centre in a university hospital. POPULATION: There were 312 singleton pregnancies in 321 women with a previous large loop excision of the transformation zone (LLETZ), and 62 pregnancies after a second-trimester miscarriage in a previous pregnancy. METHODS: The CL measurements were performed by transvaginal ultrasound at 16, 18, 20, and 22 completed weeks of gestation. MAIN OUTCOME MEASURES: Early preterm delivery before 34 completed weeks of gestation. RESULTS: Early preterm delivery was found in 7.4%. The CL at 16 completed weeks of gestation was smaller in the LLETZ group (36 mm, interquartile range 30-40 mm) compared with the control group (38 mm, interquartile range 32-42 mm; P = 0.040). For the analysis of risk factors for early preterm delivery after LLETZ, only cases with a complete data set were included (n = 145). In a multivariate analysis, two parameters remained significantly predictive, with CL at 16 completed weeks of gestation being the most significant measure (P < 0.001, OR 0.90, 95% CI 0.83-0.98), followed by conception using IVF treatment (P = 0.031, OR 0.64, 95% CI 1.54-34.80). CONCLUSIONS: Even as early as 16 weeks of gestation, women with early preterm delivery reveal a significantly lower CL than those without. Dynamics in the CL do not add to this information.

Screening of gestational diabetes mellitus in early pregnancy by oral glucose tolerance test and glycosylated fibronectin: study protocol for an international, prospective, multicentre cohort trial.

INTRODUCTION: As the accurate diagnosis and treatment of gestational diabetes mellitus (GDM) is of increasing importance; new diagnostic approaches for the assessment of GDM in early pregnancy were recently suggested. We evaluate the diagnostic power of an 'early' oral glucose tolerance test (OGTT) 75 g and glycosylated fibronectin (glyFn) for GDM screening in a normal cohort. METHODS AND ANALYSIS: In a prospective cohort study, 748 singleton pregnancies are recruited in 6 centres in Switzerland, Austria and Germany. Women are screened for pre-existing diabetes mellitus and GDM by an 'early' OGTT 75 g and/or the new biomarker, glyFn, at 12-15 weeks of gestation. Different screening strategies are compared to evaluate the impact on detection of GDM by an OGTT 75 g at 24-28 weeks of gestation as recommended by the International Association of Diabetes and Pregnancy Study Groups (IADPSG). A new screening algorithm is created by using multivariable risk estimation based on 'early' OGTT 75 g and/or glyFn results, incorporating maternal risk factors. Recruitment began in May 2014. ETHICS AND DISSEMINATION: This study received ethical approval from the ethics committees in Basel, Zurich, Vienna, Salzburg and Freiburg. It was registered under http://www.ClinicalTrials.gov (NCT02035059) on 12 January 2014. Data will be presented at international conferences and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT02035059.

Human papillomavirus in the cervix and placenta.

OBJECTIVE: To determine the prevalence and association of human papillomavirus (HPV) infection in the cervices and placentas of pregnant women. METHODS: Cervical samples were taken from 179 of 226 women who had placental biopsies because of abnormal ultrasound findings or were older than 35 years, to detect HPV infections with hybrid capture II tests. Polymerase chain reaction (PCR) was done on placental tissue of 147 of the 226 women to detect HPV DNA. RESULTS: We found 44 of 179 women (24.6%, 95% confidence interval 18.3, 31.0) to test positive for HPV in their cervices. Logistic regression analyses showed decreased prevalence of HPV infection with increased maternal age (P =.039). The HPV DNA E6 PCR from the villus tissue was negative in the 147 cases examined. However, a significant contingency coefficient between low-risk HPV infection and elevated risk of chromosome aberration was found (φ = V = 0.15, P =.050). CONCLUSION: The infection rate of 24.6% in women without clinical symptoms of HPV infection was high, but there seemed to be no virus transmission to the placenta in women with subclinical infections. Low-risk cervical HPV infection might be associated with a slightly higher risk of abnormal fetal karyotype.

A pilot study of hormone replacement therapy with tibolone in women with mastopathic breasts.

OBJECTIVE: Our purpose was to investigate the effect of tibolone in a prospective randomized, double-blind pilot study in postmenopausal women with clinically palpable mastopathic changes. METHODS: Twenty postmenopausal non-users of hormone replacement therapy undergoing mammography were randomly allocated to receive either 2.5 mg tibolone (Livial, Organon) or placebo (2 mg lactose). Mammographic density according to the Wolfe classification, severity of breast discomfort, parity, smoking habits, body weight and follicle-stimulating hormone (FSH) and estradiol (E(2)) levels were documented at baseline and after 6 months of treatment. RESULTS: There were no statistically significant differences between the two treatment groups in terms of parity, smoking, body weight and FSH and E(2) levels. At 6 months, four patients in the tibolone group showed reduced breast density, compared with one patient in the placebo group. Whereas no significant differences were found between the two treatment groups when the categories 'minimal reduction' and 'reduction' in mammographic density were combined, combination of the categories 'no change' and 'minimal reduction' showed a significant difference (P<0.036). Also, women in the tibolone group showed a statistically significant improvement in breast discomfort (P<0.019). CONCLUSION: This pilot study showed decreases in breast density as well as an attendant significant alleviation of breast discomfort in women with baseline mastopathic changes treated with tibolone for 6 months, which may be due to the inhibitory effect of tibolone on the enzymes involved in the biosynthesis of estradiol demonstrated in previous trials and should be further evaluated in long-term studies.

The effects of hormone substitution in depot form on the uterus in a group of 50 perimenopausal women--a vaginosonographic study.

The aim of our study was to examine the effects of hormone replacement on the size of the uterus and the development or increase of myomatas. Fifty perimenopausal women were included in the study (53.8 +/- 5.0 years). Patients received a substitution therapy composed of a combination of 4 mg estradiovalerate and 200 mg prasteronenantate (Gynodian Depot cartridges) given as a muscular injection in 6-10 week intervals (mean 7 weeks +/- 4 days). Prior to the onset of therapy with Gynodian and after a period of 12 months (+/- 13 days) vaginosonography was performed. Measurements taken were length, thickness, height of endometrium, size of ovaries and of myomas. Data obtained were correlated with baseline findings. Within 1 year, significant increases in uterus length from 73.4 mm to 88.2 mm, in uterus thickness from 33.9 mm to 43.5 mm and in endometrium height from 4.1 mm to 6.7 mm were observed (median values). There was an increase in both the number (from 2.2 to 3.5) and the size of the myomatas (29.4-35.0 mm diameter). A statistical analysis conducted by means of the Wilcoxon matched pairs signed-rank sum test showed P < 0.001. No significant change occurred in the size of the ovaries. Our study shows that hormone substitution may have an impact on uterus growth and that therefore vaginosonographical monitoring can be recommended.

[Intrauterine contraception with copper-T 200 device- a retrospective analysis of 334 cases (author's transl)]. / Intrauterine Kontrazeption mit dem Kupfer-T-200-Pessar - eine retrospektive Analyse an Hand von 334 einlagen.

A review is given of the findings obtained in 334 women in whom a Cu-T 200 intrauterine device had been inserted at least two years previously and regular follow-up examinations were subsequently undertaken. The most frequent indications were an expressed preference for IUD on the patient's part (38.3%), poor tolerance to the "pill" (24.8%) and so-called "pill fatigue" (11.1%). Varicose veins led to IUD preference in 8.1% and thromboembolic disease in 6.-%. The failure rate - with 12 pregnancies - was 3.6%, all within 6 months of insertion of the device. Half of the pregnancies went to full term and resulted in the birth of mature, healthy babies. The most frequent complication were menstrual disturbances (20.1%). pain (19.5%), cervicitis (18.3%), and adnexitis (13.8%), necessitating removal of the device in 5.7%, 4.2%, 5.1%, and 0.6% of all cases for the afore-mentioned reasons, respectively. These rates are relatively high. The expulsion rate of 2.7% was relatively low, however. Further analysis of the complications led to the observation that menorrhagia was relatively common in nulliparae and in women with retroversion of the uterus, whereas the pre-insertion finding of a pressure-sensitive uterus with a normal ESR, led in a significantly higher percentage of cases to pain and adnexitis. The diagnosis by vaginal probe of a reduced uterine length led to faulty positioning and an increased tendency to pain in a significantly higher number of cases. The fact that only 56.6% of all women tolerated intrauterine contraception well and remained totally symptom-free supports th view held by us that even today the "pill" remains the contraceptive of choice and should be recommended as such.

PIP: A review is given of the findings obtained in 334 women in whom an IUD had been inserted at least 2 years previously. Regular follow-up examinations were subsequently undertaken. The most frequent indications were an expressed preference for an IUD on the part of the patient (38.3%), poor tolerance of the pill (24.8%), and pill fatigue (11.1%). Varicose veins led to IUD preference in 8.1% and thromboembolic disease in 6.0%. The failure rate, 12 pregnancies, was 3.6%, all within 6 months of device insertion. 1/2 of the pregnancies went to term and resulted in the birth of mature, healthy babies. The most frequent complications were menstrual disturbances (20.1%), pain (19.5%), cervicitis (18.3%), and adnexitis (13.8%), necessitating removal of the device in 5.7%, 4.2%, 5.1%, and 0.6% of all cases respectively. These rates are relatively high. The expulsion rate of 2.7% was relatively low. Further analysis of the complications led to the observation that menorrhagia was relatively common in nulliparae in women with a retroversion of the uterus, whereas the preinsertion finding of a pressure-sensitive uterus with a normal ESR, led in a significantly higher percentage of cases, to pain and adnexitis. The diagnosis by vaginal probe of a reduced uterine length led to faulty positioning and an increased tendency to pain in a significantly higher number of cases. The fact that only 56.6% of all women tolerated IUDs well and remained totally symptom-free, supports the view held by us that even today the pill remains the contraceptive of choice and should be recommended as such. (author's)

[Age and sex specific differences in bone density of 4,000-year-old individuals. Bone density measurement of early Bronze Age femurs from excavations in Unterhautzenthal, Lower Austria]. / Alters- und geschlechtsspezifische Unterschiede der Knochendichte von 4000 Jahre alten Individuen. Knochendichtemessung an frühbronzezeitlichen Femora von Ausgrabungen aus Unterhautzenthal, NO.

Bone density measurements of 14 individuals (early Bronze Age, 2200-1600 BC), analyzed by dual-energy absorptiometry, showed a distinct difference between women and men. In men, there was a high bone density (+17.9%-0.290 g/cm2 difference). In females, a constant decrease in bone density was found after the age of 20-25 years (from 1.2 g/cm2 at 20 years to 0.8 g/cm2 at 40 years of age). With caution, the results are comparable with those of the present time.

[Effect of high performance sports on female menstrual cycle exemplified by windsurfing]. / Der Einfluss von Leistungssport auf das weibliche Zyklusverhalten am Beispiel Windsurfen.

Questionnaires were sent to all female members (n = 60) of the Austrian Funboard Association (funboard = the most athletic windsurfing class). They included questions about the menstrual cycle, physical capacity, libido and performance dependent on the particular cycle phase. There was no significant libido or capacity peak, neither for the windsurfers nor for a normal collective (n = 100); on the other hand there was an evident low during menstruation. A mean length of the menstrual cycle of 26.5 +/- 2.8 days and a bleeding time of 4.4 +/- 1.2 days were found, while metrorrhaghia and dysmenorrhea were less frequent than in the normal collective. One reason for these findings could be that physical activity reduces dysmenorrhea.

[Effect of low birth weight on menstruation and sex behavior in adulthood]. / Die Auswirkung eines geringen Geburtsgewichtes auf das Menstruations- und Sexualverhalten im Erwachsenenalter.

We report the results of a follow-up study of women, who had low birth weight, and their later gynecological development concerning menarche, menstrual cycle, menstrual complaints, sexual activity and fertility. 50 women with a mean age of 22 years have been divided into three groups (13 women had a birth weight below 1.500 g, 17 women were within the range of 1.500 g and 2.000 g and 20 women between 2.001 and 2.500 g). Considering the parameters menarche, sexual activity and fertility no differences among those three groups were found. Comparing all three groups of low-birth-weight newborns significant differences could be shown in menstrual cycle and menstrual complaints.

Relationship of serum levels of endogenous relaxin to cervical size in the second trimester and to cervical ripening at term.

OBJECTIVE: To assess whether cervical size in the early second trimester and cervical ripening at term may be related to serum levels of endogenous relaxin, 17beta-oestradiol or progesterone. DESIGN: A cross-sectional study investigating the relationship between hormone concentrations and cervical parameters as measured by ultrasound and Bishop score, respectively. PARTICIPANTS: Uncomplicated human pregnancies with normal fetal outcome, 72 women in the second trimester and 40 women at term. METHODS: Vaginal ultrasound and palpation were used to estimate cervical parameters. Hormones were analysed either by dissociation-enhanced fluoroimmunoassay (relaxin) or by automated electrochemiluminescent immunoassays. RESULTS: Cervical length and diameter correlated positively during mid-gestation and negatively at term. During mid-gestation, but not at term, relaxin was significantly associated with cervical length and volume, and with progesterone. Bishop score only correlated inversely with progesterone at term. CONCLUSION: Corpus luteum function is reflected by progesterone and relaxin in the early second trimester. An impact of relaxin on cervical growth, previously demonstrated by animal models and in vitro experiments, was confirmed during human mid-gestation. In contrast to many other species, human cervical ripening was not associated with endogenous relaxin at term, but with decreased progesterone.

The influence of nicotine abuse and diabetes mellitus on the results of primary irradiation in the treatment of carcinoma of the cervix.

References in the literature to the frequent occurrence of cervix carcinoma accompanied by nicotine abuse led us to investigate the effects of cigarette smoking on the results of treatment in primary irradiation of cervix carcinoma. As not only nicotine abuse but also diabetes mellitus can lead to angiopathy, we also investigated the influence of diabetes mellitus on the results of treatment. Of 410 nonsmokers with carcinoma of the cervix in Stages I and II, 260 (63.4%) reached the 5-year limit, but only 62 of 115 smokers survived (53.9%). In Stages III and IV there were significantly less favorable rates of cure in patients with nicotine abuse. Of 626 nonsmokers with cervix carcinoma in Stages III and IV, 212 survived (33.9%); but of 153 smokers, only 31 (20.1%) could be cured (P less than 0.01). The frequency of side effects of primary irradiation was distinctly higher in smokers than in nonsmokers. Reversible complications occurred in 17.5% of the smokers and 15.5% of the nonsmokers. Severe irreversible changes occurred in 28% of the smokers versus 15.2% of the comparative group of nonsmokers (P less than 0.01). The injuries caused by smoking not only reduce the biologic effectiveness of ionizing radiation but also increase the rate of side effects due to the deficient capacity for regeneration of the tissue surrounding the tumor. With diabetes as a complication, however, no significant changes in frequency of side effects were noted. Five-year survival in diabetic patients was affected in Stage I and II, but not in the advanced stages.

[Vaginal ultrasound study of the normal and incompetent cervix: attempting a mathematical assessment]. / Vaginosonographische Studie bei normaler und inkompetenter Zervix: Versuch einer mathematischen Beurteilung.

A group of 217 pregnant patients was examined by vaginosonography. The group could be divided into 62 patients with incompetent cervix and 155 patients with normal findings. We measured the width of the internal os, the length and the thickness of cervix of all patients in intervals of 14 days. We registered a dynamic process pattern of cervical, morphological changes in the group with preterm delivery. We tried to reduce these cervical changes to an arithmetic formula.

[Effects of prostaglandin E1 analogs on the cervix--observations with vaginal sonography]. / Der Einfluss von Prostaglandin-E-1 Analoga auf die Zervix--Beobachtungen mit der Vaginosonographie.

In this study participated 17 patients, in whose pregnancies not viable malformations or intrauterine deaths were diagnosed. The termination of the pregnancies was done with PG-E-1 suppositories Gemeprost (Cergem) 1 mg. Collectively the patients received 3 Cergem suppositories applicated all 3 hours. Before beginning therapy and every 4-6 hours a vaginosonography was done. The cervical changes under the influence of Gemeprost were documented vaginosonographically. The measurements before Gemeprost treatment showed an average cervical length of 44.2 +/- 6.3 mm, a width of 29.5 +/- 1.7 mm and an internal os of 2.5 +/- 0.5 mm. The results of the second ultrasound showed a length of 30.6 +/- 4.1 mm, a width of 32.3 +/- 2.5 mm and an internal os of 7.0 +/- 3.0 mm. The last measurements (ca. 107 minutes before abortion) showed a remaining of cervical length of 15.2 +/- 4.5 mm, a width of 41.5 +/- 4.6 mm, an internal os of 19.2 +/- 4.1 mm and the amniotic membranes bulged into the cervical channel.

[Contraception in preclimacteric women with special regard to oral contraceptives (author's transl)]. / Kontrazeption bei der Frau im Präklimakterium unter besonderer Berücksichtigung der Ovulationshemmer.

During a period of 9 years 143 women at an age over 40 attended for the first time the I. University Clinic of Gynecology and Obstetrics in Vienna for receiving contraceptive treatment. 71 women (49.6%) received oral contraceptives wiD was inplanted because of either internal contraindications of oral contraceptives (mainly high risk for thrombosis) or negation by the patient. 16 patients were sterilised, mostly with the laparascope. The main side effects in the patients receiving oral contraceptives were nervosity, impairment of libido and complaints in the lower extremities. 60.5% of all women over the age of 40 using oral contraception didn't show any complaints. On the basis of the own results and the reports in literature the advantages and disadvantages of oral contraception in comparison with mechanical devices are discussed.

[Vaginosonographic imaging of the endometrium of postclimacteric females]. / Vaginosonographische Darstellung des Endometriums postklimakterischer Frauen.

Vaginal sonography of the endometrium is a new method of controlling the substitution therapy with oestrogen and progesterone during the postmenopausal period. The advantages of transvaginal ultrasonic diagnosis are that the uterus can be seen from the fornix vaginae, that it is situated at close range, and that the examination can be conducted whether the bladder is filled or not. The differences in thickness and structure of the endometrium, and the limitation to the surrounding myometrium, enable sonographic detection of most of the changes of the endometrium during the postmenopausal period. In our first group of patients, we found an endometrial carcinoma in 2 out of the 60 women with postmenopausal metrorrhagia. The findings were confirmed histologically. Women who have regular bleedings while undergoing hormone therapy during the postmenopausal period, show signs of proliferation in the endometrium under oestrogen therapy and signs of secretion under progesterone therapy.

[Vaginal ultrasound studies of cervix closure with special reference to parity]. / Vaginosonographische Beobachtungen des zervikalen Verschlussapparates unter besonderer Berücksichtigung der Parität.

In this study, the cervical length, thickness, the width of the internal os, the cervical canal and the external os of 62 primipara and 77 multipara were measured vaginosonographically. Only patients with normal pelvic scores were examined. The measurements were carried out approx. every fortnight between the 16th and 34th gestational week. In the primipara group, the average cervical length was 36.8 mm +/- 12.0 mm, the thickness 27.8 mm +/- 4.4, the width of the internal os 6.3 +/- 2.1 mm, the cervical canal 4.2 +/- 2.0 mm and the external os 5.4 +/- 2.2 mm. In the multipara group, an average cervical length of 40.1 mm +/- 7.4 mm, a thickness of 29.3 +/- 3.9 mm, an internal os of 5.1 +/- 2.6 mm, a cervical canal of 4.3 +/- 1.3 mm and an external os of 5.8 +/- 1.8 mm were found. Contrary to our expectations, there was no statistically significant difference between the two groups. Furthermore we did not find any correlation between the internal and the external os.

[Dynamic measurement of surface tension versus gas chromatography dipalmitoylphosphatidylcholine analysis of amniotic fluid; a comparison of a bedside method with a highly specialized surfactant analysis]. / Dynamische Oberflächenspannungsmessung versus gaschromatographische DPPC-Analyse im Fruchtwasser; ein Vergleich einer "Bedside" Methode mit einer hochspezialisierten Surfactantanalyse.

The diagnosis of fetal lung maturity by analysis of the amniotic fluid still constitutes a present-day problem. In this study the results of measuring the dynamic surface tension by the Wilhelmy-balance were compared with the DPPC (Dipalmitoyl-Phosphatidyl-Choline) and lecithin species-analysis by the quantitative capillary gas chromatography. The first possibility is a "bed-side"-method, which evaluates the effect of the surfactant in the amniotic fluid in its entirety, whereas the second method represents a highly specialized laboratory procedure analysing the most important part of surfactant contact. The surface tension of amniotic fluid is expressed by its value at 20% of the extension of the surface (gamma-min) as well as the hysteresis area. We were able to show a better correlation between the hysteresis area and the DPPC (r = 0.422, p less than 0.012) than between the gamma min and the DPPC (r = 0.370, p less than 0.031). The correlation between the hysteresis area respectively between the gamma-min, and the second gas chromatographically detectable component of the surfactant, PC 30 was not so distinct (r = 0.068, p less than 0.744; R = -0.355, p less than 0.075). Obviously this component of the surfactant is not as active on the surface and therefore not as important. Further we could show, a negative correlation to the lecithin species PC 34; with increasing surface activity and increasing lung maturity this lecithin species quantitatively recedes into the background.