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Werner Rath

Publications and source records attributed to Werner Rath.

At least 19 recordsLinked to original sources
PubMed2006

Tubal abortions but not viable tubal pregnancies are characterized by an increased number of CD8+ T cells.

OBJECTIVE: To examine immune cell phenotypes in viable tubal pregnancies (VTP) and in tubal abortions (TA). METHODS: Paraffin-embedded specimens of VTP (n=7) and ongoing TA (n=6) were double-stained for cytokeratin for trophoblast as well as for CD45, CD3, CD8, CD68 and CD20 for immune cell phenotypes. In all cases, the amniotic sac was detected by ultrasound. Histological examination showed no evidence of necrosis within the tissues included in this study. Quantification of the subpopulations was performed in each slide by two independent examiners in five areas (0.085 mm2 each) of the invasion zone as marked by cytokeratin-positive stromal extravillous trophoblast (EVT) cells. For statistical analysis, the non-parametric two-tailed t-test was used (p<0.05). RESULTS: The differences in the number of CD45(+), CD68(+) and CD20(+) cells was significant (p=0.0423, p=0.0469 and p=0.0494, respectively); however, the number of CD3(+), and among those the number of CD8(+) cells, was approximately eight-fold higher in TA than in VTP (p<0.0001 and p=0.0012, respectively). CONCLUSION: The unequal distribution of CD8(+) cells in VTP and TA suggests a significant role of this immune cell phenotype in the further outcome of a tubal pregnancy either to an abortive or a viable, potentially life-threatening, entity.

Abortion, Spontaneous↗
PubMed2006

Expression of the actin stress fiber-associated protein CLP36 in the human placenta.

Differentiation processes in the trophoblast comprise polarization, cell fusion and migration. All these processes involve dramatic reorganizations of cytoskeletal proteins such as intermediate filaments or actin. Due to very restricted knowledge on cytoskeletal changes in trophoblast, we analyzed the protein expression of an actin stress fiber-associated protein, the carboxy-terminal LIM domain protein (CLP36). CLP36 belongs to the enigma family of proteins, binds to alpha-actinin and is involved in the cytoskeletal reorganization and signal transduction of a variety of cells. CLP36 protein was found to be exclusively expressed in the cytotrophoblast layer. Colocalization of CLP36 with Mib-1 revealed that CLP36 protein expression is restricted to proliferative and early post-proliferative trophoblast cells. Blockage of syncytial fusion by culture of villous explants in the presence of caspase 8 inhibitors further supported this notion since CLP36 was only found in the basal and proliferative layer of the multilayered cytotrophoblast. We present evidence for the exclusive protein expression of CLP36 in proliferative and early post-proliferative trophoblast cells. Pathological pregnancy syndromes such as preeclampsia are driven by alterations of trophoblast differentiation and turnover, where it needs to be elucidated whether CLP36 is involved in these alterations.

Actins↗
PubMed2006

The significance of under- or overweight during childhood as a risk factor for hypertensive diseases in pregnancy.

Hypertensive diseases in pregnancy are still a major cause of foetal and maternal mortality. Known risk factors allow identification of only a small number of patients at risk of developing such a complication. However, better knowledge of the risk profile would improve an early adequate monitoring of these pregnancies. We therefore investigated the correlation between under- or overweight during childhood and the development of hypertensive diseases during pregnancy. The study was designed as a cross-sectional case control study. A self-administered questionnaire was distributed to 2600 women, who had contacted the German pre-eclampsia self-help group for information on hypertensive diseases in pregnancy and 1233 control women recruited in different hospitals. Diagnosis according to criteria of the international society for hypertensive diseases in pregnancy was based on medical records. 766 women with a hypertensive disease during their pregnancy and 951 control women with normal pregnancies were evaluated after verifying for exclusion criteria and complete data sets. Student t-test, chi square test and multivariate logistic regression models were used for statistical analysis. A history of under- (OR 2.1, 95% CI 1.23-3.61) or overweight (OR 1.46, 95% CI 1.01-2.12) during childhood is associated with an increased risk for hypertensive diseases in pregnancy, which is at least partly independent of pre-pregnancy BMI. In combination with other risk factors, a history of under- or overweight during childhood will help to identify patients at risk for hypertensive diseases in pregnancy.

Adult↗
PubMed2006

Satisfaction with medical information in women with hypertensive disorders in pregnancy.

OBJECTIVE: Hypertensive disorders in pregnancy (HDP) are a major cause of maternal death and fetal prematurity. The purpose of this study was to examine HDP patients' reported satisfaction with the medical information provided by their health care providers. METHODS: A convenient sample of N=620 patients with a diagnosis of HDP within 24 months prior to the study period completed a self-administered questionnaire dealing with the medical information received and their reported satisfaction. Chi-square, Fisher's Exact, and Student's t tests were used to determine the differences in sociodemographic data and potential confounders between HDP patients who were satisfied and dissatisfied with medical information. RESULTS: Of the women, 68.6% were not satisfied with the medical information. Women were particularly dissatisfied when they suffered from preeclampsia (PE), were informed of their actual situation, including eventual consequences only after delivery, and in case of fetal disorders resulting from HDP. CONCLUSION: Based on the background information reported on the importance of medical information to the patient, women developing HDP should be informed of their disease and potential sequelae as early and as differentiated as possible. Doctors need to be convinced of the role of the provider in counseling women with HDP. Information has to be repeated and health care providers are supposed to check whether the women understood the information received.

Adult↗
PubMed2006

Influence of childhood sexual abuse on pregnancy, delivery, and the early postpartum period in adult women.

OBJECTIVE: With a prevalence of around 20%, childhood sexual abuse (CSA) is a relevant problem in obstetric care. The aim of our systematic review was to present the current knowledge on the influence of CSA on pregnancy, delivery, and early parenthood. DATA SOURCES: All English, French, or German primary and secondary literature from the reference lists found after screening the data banks Pubmed, PsycInfo, and Psyndex for publications that include the terms CSA or childhood traumatization and pregnancy, birth, delivery, labor, childbearing, breast feeding, or postpartum, and published after 1970 were reviewed for relevant data. METHODS OF STUDY SELECTION: Investigations of psychological/medical data banks and cross references revealed 43 relevant studies. Given the paucity of data on this important subject, we opted to review all of these studies. TABULATION, INTEGRATION, AND RESULTS: Although research projects on this topic are rare and the methodological quality of studies published to date is generally poor, women with a history of CSA seem to present a variety of long-term sequelae referring to pregnancy, delivery, and early parenthood. These sequelae include risk behaviors during pregnancy and disturbance of delivery by sudden memories of sexual abuse situations. Prenatal care is often complicated by the tendency to avoid situations that can trigger memories. CONCLUSIONS: As effective treatment programs to improve sequelae of CSA are available today, the question of such abuse experiences should be raised as early as possible and adequate interdisciplinary models to care for victimized patients should be established. However, to improve knowledge on the long-term effect of sexual abuse experiences in obstetrical care, methodologically well-designed research projects focusing on the kind and incidence of sequelae, mediating factors as well as prophylactic and therapeutic options are needed.

Adolescent↗
PubMed2006

BMI: new aspects of a classical risk factor for hypertensive disorders in pregnancy.

HDP (hypertensive diseases in pregnancy) are one of the leading causes of maternal and fetal mortality and morbidity. BMI (body mass index) is an established risk factor for pre-eclampsia, but its role in HELLP syndrome is unknown. We therefore investigated BMI as a risk factor in the development of HELLP syndrome. At the beginning of pregnancy, BMI was measured in 1067 women with a history of HDP and 1063 controls. Diagnoses of HDP were classified according to ISSHP (International Society for the Study of Hypertension in Pregnancy) and BMI according to WHO (World Health Organization) criteria. After verification of exclusion criteria and matching for confounders, 687 women with hypertensive diseases in pregnancy and 601 controls remained for statistical evaluation by chi(2) test and multiple logistic regressions. As a continuous variable, the increase in BMI was associated with an increase in the development of gestational hypertension {OR (odds ratio), 1.1 [95% CI (confidence interval) 1.062-1.197]} and pre-eclampsia [OR, 1.1 (95% CI, 1.055-1.144)]}, but not for HELLP syndrome. According to WHO definitions, overweight women (BMI > or =25 and <30 kg/m(2)) had a 2-fold (95% CI, 1.365-2.983) risk and obese women (BMI > or =30 kg/m(2)) had a 3.2-fold (95% CI, 1.7-5.909) risk of developing pre-eclampsia when compared with women of normal weight (BMI > or =15.5 and <25 kg/m(2)). Being overweight or having obesity had no effect on the risk of HELLP syndrome. As an increased BMI is correlated with the risk of developing pre-eclampsia but not HELLP syndrome, both diseases have a different risk profile. This finding supports that underlying physiological mechanisms in pre-eclampsia vary from those in HELLP syndrome.

Adult↗
PubMed2006

Smoking and the risk of developing hypertensive diseases in pregnancy: what is the effect on HELLP syndrome?

BACKGROUND: The aim of our study was to investigate the role of smoking in the development of HELLP syndrome, pre-eclampsia and gestational hypertension. METHODS: A self-administered questionnaire was sent to 2,600 women who had contacted the German Pre-eclampsia Self-help Group previously for information on hypertensive disorders in pregnancy and to 1,233 controls. Diagnoses were verified by reviewing medical records and classified according to ISSHP criteria. Student's t-test, Wilcoxon test, Chi-square test, and multiple logistic regressions were used for statistical analysis. RESULTS: After matching age, parity, nationality, and education a total of 905 women with a hypertensive disease in pregnancy and 945 controls were evaluated for the present study. In comparison to the patients, controls smoked significantly more often during their pregnancies (8.5%/18%, p<0.0001). Smoking during pregnancy was associated with a decreased risk of developing hypertensive disorders in pregnancy by 56%. The most prominent effect of smoking was on the risk of developing HELLP syndrome (OR 0.19, 95% CI 0.08-0.43) followed by HELLP syndrome + pre-eclampsia (OR 0.33, 95% CI 0.17-0.63), pre-eclampsia only (OR 0.46, 95% CI 0.26-0.8), and gestational hypertension (OR 0.66, 95% CI 0.41-1.08). CONCLUSIONS: Smoking is associated with an 80% reduction of the risk developing HELLP syndrome. However, pregnant women should be advised to quit smoking. Understanding the different effects of smoking in the etiology of each subtype of hypertensive diseases in pregnancy will improve the knowledge of underlying pathophysiological mechanisms and may help in designing more effective prevention and treatment strategies.

Adult↗
PubMed2006

Altered protease expression by periarterial trophoblast cells in severe early-onset preeclampsia with IUGR.

Adaptation of uteroplacental arteries in patients with early-onset preeclampsia combined with IUGR is compromised due to insufficient invasion of extravillous trophoblast cells (EVT) into the spiral artery wall. The underlying molecular mechanisms are widely unknown. We investigated expression and possible mechanisms of regulation of different matrix-metalloproteases (MMPs) by EVT in placental bed biopsies from patients with early onset preeclampsia combined with IUGR and healthy pregnant women. Expression of MMP-3 and MMP-7 by EVT was markedly reduced in preeclamptic patients, especially close to spiral arteries. In contrast to healthy pregnancies these cells strongly expressed the receptor for leukemia inhibitory factor (LIF). LIF is known to suppress MMP-expression and is produced by uterine natural killer (uNK) cells which we found to be present in higher concentrations in the placental bed of preeclamptic patients, and accumulating aside the spiral arteries. We speculate that in preeclampsia a maternal immune cell network accumulating and interfering in the placental bed leads to an altered cytokine environment, resulting in disturbed trophoblast cell function such as impaired MMP expression and reduced invasiveness.

Apoptosis↗
PubMed2005

Concerted upregulation of CLP36 and smooth muscle actin protein expression in human endometrium during decidualization.

The human endometrium prepares for implantation of the blastocyst by reorganization of its whole cellular network. Endometrial stroma cells change their phenotype starting around the 23rd day of the menstrual cycle. These predecidual stroma cells first appear next to spiral arteries, and after implantation these cells further differentiate into decidual stroma cells. The phenotypical changes in these cells during decidualization are characterized by distinct changes in the actin filaments and filament-related proteins such as alpha-actinin. The carboxy-terminal LIM domain protein with a molecular weight of 36 kDa (CLP36) is a cytoskeletal component that has been shown to associate with contractile actin filaments and to bind to alpha-actinin supporting a role for CLP36 in cytoskeletal reorganization and signal transduction by binding to signaling proteins. The expression patterns of CLP36, alpha-actinin and actin were studied in endometrial stroma cells from different stages of the menstrual cycle and in decidual stroma cells from the 6th week of gestation until the end of pregnancy. During the menstrual cycle, CLP36 is only expressed in the luminal and glandular epithelium but not in endometrial stroma cells. During decidualization and throughout pregnancy, a parallel upregulation of CLP36 and smooth muscle actin, an early marker of decidualization in the baboon, was observed in endometrial decidual cells. Since both proteins maintain a high expression level throughout pregnancy, a role of both proteins is suggested in the stabilization of the cytoskeleton of these cells that come into close contact with invading trophoblast cells.

Actinin↗
PubMed2005

A clinical evaluation of controlled-release dinoprostone for cervical ripening--a review of current evidence in hospital and outpatient settings.

Labor induction is used in approximately 20% of pregnancies in Europe and North America. Prostaglandins and prostaglandin analogs are favored when women undergoing labor induction have an unripe cervix. Controlled-release dinoprostone, delivered over 24 h from a vaginal insert, results in cervical ripening within 12 h in most women. It is marginally more effective than immediate release formulations and has similar efficacy to misoprostol, a prostaglandin E1 analog used off-label for this indication. The controlled-release preparation offers many advantages compared with an immediate-release formulation: a single application is sufficient; it is less invasive; it is easily administered and removed, allowing greater dose control. The most significant adverse effect, uterine hyperstimulation, with and without an effect on fetal heart rate, occurs in 5-15% of patients, which is comparable with other formulations or misoprostol. The insert can be removed easily on the first sign of uterine hyperstimulation, or as soon as labor starts. The efficacy and safety of controlled-release dinoprostone are comparable whether it is used in the outpatient or the inpatient setting. For low-risk women, outpatient use may be a highly attractive option, potentially reducing hospital costs, and improving patient convenience. The ease of use of controlled-release dinoprostone and women's satisfaction emphasize its benefits over many other agents used to ripen the cervix.

Ambulatory Care↗
PubMed2005

Breast-feeding in women with hypertensive disorders in pregnancy.

AIMS: Breast feeding is particularly important and difficult in children born prematurely, especially after hypertensive diseases in pregnancies (HDP). Therefore, we aimed to investigate breast feeding in women who developed HDP. METHODS: Data on breast-feeding was collected within a nationwide research project on psychosocial factors in HDP. A self-administered questionnaire was given to 2600 women with a suspected history of HDP and 1233 controls. After matching and confirming diagnosis according to ISSHP criteria, 877 women with HDP and 623 controls were included into the study. RESULTS: Control women initiated (48.9/39.2%; P<0.001) and continued (42.2/37.2%; P<0.005) breast-feeding significantly more often than women with HDP. This holds particularly for women who developed HELLP syndrome (48.9/34.7%; P<0.0001, 42.2/33.5%; P<0.0001). A delivery before the 32(nd) gestational week (19.5/81.8%; P<0.0001) and a birth weight of less than 1500 g (18.8/75%; P<0.0001) were associated with the decision not to breast-feed. CONCLUSIONS: Women affected by HDP breast fed significantly less often than control women. This effect is at least partly caused by the increased rate of prematurity. Encouraging and supporting these women in breast-feeding is important to improve neonatal physical and mental development.

Adult↗
PubMed2004

FDG PET and tumour markers in the diagnosis of recurrent and metastatic breast cancer.

Breast cancer continues to be one of the most common cancers in North America and Western Europe. Positron emission tomography with 2-[fluorine-18]-fluoro-2-deoxy-D-glucose (FDG PET) represents a non-invasive functional imaging modality that is based on metabolic characteristics of malignant tumours. In breast cancer, FDG PET is more accurate than conventional methods for staging of distant metastases or local recurrences and enables early assessment of treatment response in patients undergoing primary chemotherapy. Recent data indicate a rationale for the use of FDG PET in cases of asymptomatically elevated tumour marker levels in the presence of uncertain results of conventional imaging. Despite the fact that PET cannot rule out microscopic disease, it does have particular value in providing, in a single examination, a reliable assessment of the true extent of the disease. This technique is complementary to morphological imaging for primary diagnosis, staging and re-staging. It may become the method of choice for the assessment of asymptomatic patients with elevated tumour marker levels. This method, however, cannot replace invasive procedures if microscopic disease is of clinical relevance.

Biomarkers, Tumor↗
PubMed2004

Ki67, HSP70 and TUNEL for the specification of testing of silicone breast implants in vivo.

This investigation of capsular tissue adjacent to silicone breast implants concerns the long-term tissue response to the implant environment. Fifty-three silicone breast implants have been analyzed at the time of explantation. The implant duration ranged from 2 months to 153 months. The reason for explantation was capsular contracture (57%), dissatisfaction with the effect (11%), local inflammation (6%), implant rupture (4%) and exchange of tissue expanders (21%). The cell turnover within the interface of the silicone device and the fibrous capsule was detected by specific antibodies against Ki67 for cell proliferation, by TUNEL for apoptosis, and by DNA strand breaks and heat shock protein 70 (HSP70) for cell stress. We found a negative correlation between the expression of HSP 70 and the capsular thickness (p < 0.043) and decreased levels in specimens obtained from Baker IV implant capsules. Ki67, and TUNEL were significantly positive (p < 0.001 for both) and HSP 70 were significantly negative (p < 0.001) with signs of inflammation. Both Ki67 and TUNEL indicated decreasing values over time. Ki67 and TUNEL showed no correlation with clinical signs of implant failure, such as the Baker score. The expression of HSP70, on the other hand, was connected with structural changes of the implant capsule, in terms of capsular thickness and the Baker score.

Adult↗
PubMed2004

Her-2/neu gene amplification and protein expression in primary male breast cancer.

The role of HER-2/ neu in male breast cancer is not well defined. The purpose of the current study was to measure the frequency of HER-2/ neu expression in primary male breast cancer, to demonstrate HER-2/ neu gene amplification in cases found to be positive for protein overexpression, and to correlate HER-2/ neu positivity with clinicopathological variables. Formalin-fixed, paraffin-embedded archival material from 99 primary male breast carcinomas was evaluated by immunohistochemistry (IHC) using the HercepTest (DAKO Corp., Hamburg, Germany). Scoring was performed according to established guidelines. All cases demonstrating HER-2/ neu staining by IHC (1+/2+ and 3+) were analyzed for HER-2/ neu gene amplification by fluorescence in situ hybridization (FISH) utilizing the PathVysion assay (Vysis Corp., Downers Grove, Illinois) to assess HER-2/ neu amplification status. The immunohistochemical staining of the HER-2/ neu protein revealed HER-2/ neu positivity in 15/99 (15.1%) cases, eight tumors showed 2+ and 7 tumors 3+ staining. HER-2/ neu gene amplification was observed in 11/99 cases (11,1%), and all of the 3+ and 4/8 from the 2+ cases were amplified. HER-2/ neu gene amplification/protein overexpression did not correlate with tumor state, histological grade or estrogen/progesterone receptor status nor the axillary lymph node status. This is the first comprehensive study of HER-2/ neu gene amplification by FISH analysis in primary male breast cancer. Compared to female primary breast cancer the percentage of HER-2/ neu positivity in our study was lower. Our data provide first evidence for HER-2/ neu gene amplification in male breast cancer. Further studies should be addressed on the potential application of the monoclonal rhuMAB HER-2/ neu antibody for treatment of HER-2/ neu positive male breast cancer.

Adult↗
PubMed2004

GLUT1 mRNA and protein expression in ovarian borderline tumors and cancer.

OBJECTIVES: Increased glucose uptake and utilization is a major feature of malignant tumors. Recent studies suggest that the key mechanism of enhanced glucose metabolism in carcinoma cells involves the overexpression of transmembrane glucose transporter proteins (GLUTs). The aim of the present study was to analyze the expression of different GLUT isoforms (GLUT1-4) and to investigate whether alterations in their expression pattern accompany the malignant transformation and progression of ovarian cancer. METHODS: Tumor tissue of 94 patients suffering from primary ovarian cancer (n = 78) or borderline tumors (n = 16) and tissue from 16 patients with benign ovarian changes were examined in this study. Immunohistochemistry was performed using polyclonal GLUT1-4 antibodies. GLUT1 protein expression was quantified by Western blot analysis. GLUT1 mRNA expression was analyzed by mRNA in situ hybridization. RESULTS: All of the invasive carcinomas were positive for GLUT1. In contrast, GLUT1 expression was moderate in borderline tumors and weak to negative in all benign ovarian neoplasms. High GLUT1 mRNA levels were observed only in ovarian cancer. The intensity of GLUT1 expression in malignant ovarian neoplasms was associated neither with tumor characteristics nor with patient survival. Only GLUT3 revealed weak but homogeneous expression in human ovarian cancer as well as in benign ovarian tumors. GLUT2 and GLUT4 showed no expression in ovarian tissue. CONCLUSIONS: GLUT1 mRNA and protein were found to be expressed specifically in primary ovarian cancer. The close relationship between GLUT1 mRNA and protein expression points towards the potential relevance of GLUT1 as a diagnostic tool and therapeutic target in ovarian cancer.

Adult↗
PubMed2004

HELLP syndrome, multifactorial thrombophilia and postpartum myocardial infarction.

A case of postpartum acute myocardial infarction with intraventricular thrombus occurred in a woman with HELLP syndrome. Since coronary artery disease was ruled out angiographically, the assumed pathophysiological mechanism for myocardial malperfusion was intermittend coronary vasospasm and thrombosis. There were several thrombophilic risk factors detectable (heterozygous factor V Leiden, low levels of antithrombin III, protein S deficiency), whose possible impact in this rare but severe clinical condition is discussed.

Adult↗
PubMed2003

Histological analysis of silicone breast implant capsules and correlation with capsular contracture.

BACKGROUND: A study was undertaken to investigate long-term histological changes in the environment of breast implants and their correlation with complains at the time of capsular contracture defined by the Baker score. METHOD: The collagenous capsules of 53 silicone breast implants from 43 patients (23 smooth and 30 textured devices) were evaluated histologically for capsular thickness, the presence of histiocytes, the amount of silicone and calcification in the capsule, and the presence of synovial-like metaplasia of the inner surface of the capsule with light microscopy and polarised light. All parameters were correlated with the Baker score. RESULTS: A significantly higher degree of the Baker score was found with increasing patient age (p<0.001), implant duration (p<0.02), and capsular thickness (p<0.009). A trend towards greater capsular thickness was documented in patients who had a breast augmentation for cosmetic reasons. Synovial-like metaplasia was seen in 28 capsules (52.8%). The highest incidence was found in textured implants with a duration of less than 5 years. Histiocytic inflammation was more common in patients with clinical symptoms (p<0.001) and around subglandular implants (p<0.096). CONCLUSIONS: The histological findings of breast capsules were related to: the nature of the device surface (smooth versus textured), implant duration, and the degree of capsular contracture. Capsular contracture (Baker score of 3 or 4) was related to implant duration, capsule thickness, patient age, and inflammation.

Adult↗