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Biomedical subjects

W Rath

Publications and source records attributed to W Rath.

At least 55 records · Page 3Linked to original sources
PubMed2000

Regulation of interleukin-8 synthesis in human lower uterine segment fibroblasts by cytokines and growth factors.

OBJECTIVE: To investigate the influence of lipopolysaccharide, cytokines, growth factors, and progesterone on the synthesis of interleukin-8 by human lower uterine segment fibroblasts. METHODS: Fibroblasts derived from a lower uterine segment biopsy specimen obtained from a woman undergoing elective cesarean delivery at term were exposed to lipopolysaccharide, interleukin-1beta, transforming growth factor-beta(1), platelet-derived growth factor-AB, and combinations of these substances. All experiments were performed in the absence and presence of progesterone. The concentration of interleukin-8 in the culture medium was determined by enzyme immunoassay after 24 hours. RESULTS: Compared with controls (0.71 +/- 0.04 ng interleukin-8/10(6) cells), fibroblasts exposed to lipopolysaccharide, transforming growth factor-beta(1), or platelet-derived growth factor-AB exhibited no increase, or at most, only a minor but significant increase, in interleukin-8 secretion. Incubation with interleukin-1beta led to a moderate increase, whereas the combinations interleukin-1beta/transforming growth factor-beta(1) (105.0 +/- 7.5 ng interleukin-8/10(6) cells) and interleukin-1beta/platelet-derived growth factor-AB (387.3 +/- 25.6 ng interleukin-8/10(6) cells) increased interleukin-8 secretion dramatically. No further increase was observed with the combination interleukin-1beta/platelet-derived growth factor-AB/transforming growth factor-beta(1). When progesterone was added, interleukin-8 secretion decreased significantly by 16-34%, depending on the stimulator, or did not change. CONCLUSION: The findings indicate that interleukin-8 secretion by human lower uterine segment fibroblasts in vitro is upregulated by interleukin-1beta, transforming growth factor-beta(1), and platelet-derived growth factor-AB in a synergistic fashion. Because interleukin-8 mediates the invasion of neutrophils into the cervical stroma, this may be an important mechanism controlling cervical dilatation during parturition.

Adult↗
PubMed2000

Clinical value of detecting microalbuminuria as a risk factor for pregnancy-induced hypertension in insulin-treated diabetic pregnancies.

OBJECTIVE: We evaluated the role of clinical non-overt stage III diabetic nephropathy concerning the development of more frequent hypertensive complications during pregnancies of women requiring insulin. METHODS: 122 unselected pregnant women treated with insulin were enrolled in the study, of whom 56 were type-1 diabetic patients and 66 patients had gestational diabetes. In 24-h urine samples, excretion rates of albumin (UAE) and beta(2)-microglobulin were determined by nephelometric analysis and a radioimmunoassay, respectively. These parameters were also measured in the serum as well as HbA(1c), fructosamine and daily blood glucose profiles. RESULTS: Sixteen (15.7%) women had an elevated UAE (>30 mg/24 h), of whom three had macroalbuminuria (UAE>300 mg/24 h). Thirteen (12.7%) insulin-treated women showed microalbuminuria during pregnancy, eight with type-1 diabetes and five with gestational diabetes requiring insulin. In the entire group hypertension was observed in seven (6.9%) women of whom six had microalbuminuria. The sensitivity and specificity were 85.7% and 92.6%, respectively. The positive predictive value reached 46.2%, whereas the negative predictive value was 98.9%. CONCLUSION: Measurement of UAE in diabetic pregnancies seems to be an useful additional parameter for risk evaluation of hypertensive disorders.

Adolescent↗
PubMed2000

The endometrium as a novel target for leptin: differences in fertility and subfertility.

Leptin and its receptor are involved in endocrine and paracrine regulation of metabolism, obesity and reproduction. Here, we describe the detection of the functional long isoform receptor of leptin in human endometrium. The leptin receptor protein was shown to be expressed in glandular and luminal epithelium and is periodically regulated throughout the menstrual cycle, demonstrating main expression in follicular and mid-luteal phase. In contrast, leptin receptor mRNA is detectable by reverse transcription-polymerase chain reaction (RT-PCR) as a constitutive component. Since RT-PCR analyses showed that leptin is not expressed in this tissue, the present study suggests that the human endometrium is a novel target for leptin. Therefore, we investigated 11 subfertile patients who underwent two biopsies in one menstrual cycle. The patients presented with a repetitive endometrial maturation defect, but showed adequate serum hormone concentrations and normal steroid hormone receptor expression and down-regulation in the endometrium. These patients were, however, deficient for expression of the functional leptin receptor. These analyses provide evidence that the lack of the leptin receptor in an ovulatory cycle may contribute to subfertility by a yet undefined 'endometrial factor'.

Adult↗
PubMed2000

HELLP syndrome.

HELLP syndrome is a serious, life-threatening form of pre-eclampsia with a typical laboratory triad. The incidence of the disease is reported as being 0.17-0.85% of all live births. There has been, to date, neither reliable early recognition nor effective prevention of HELLP syndrome. As a result of endothelial dysfunction, activation of intravascular coagulation occurs with fibrin deposition in the capillaries and consecutive microcirculation disorders. The disease manifests itself on average between 32-34 weeks' gestation. HELLP syndrome will occur postpartum in up to 30% of the cases. The clinical cardinal symptom of the disease is right upper quadrant pain or epigastric pain accompanied with nausea, vomiting and malaise. In 20% of the cases with HELLP syndrome there is no hypertension and 5-15% of the pregnant patients present a low level of proteinuria or none at all. The early recognition of hemolysis is most sensitively managed by the determination of the serum haptoglobin. The increase of the aspartate transaminase (AST) and the alanine transaminase (ALT) often precedes a decrease in platelets. The course of HELLP syndrome is incalculable. It is universally agreed that a pregnancy from 32-34 weeks should be immediately delivered. Before 32-34 weeks, expectant management is generally possible in a perinatal center. The frequency for a repeated hypertensive disease in pregnancy ranges from 27% to 48%.

Diagnosis, Differential↗
PubMed2000

[Ovarian mucinous adenocarcinoma, mucocele of the appendix and pseudomyxoma peritonei: case report with immunohistochemical analysis].

Women with pseudomyxoma peritonei may have both, appendiceal and ovarian mucinous tumors, and there is a considerable debate regarding the site of origin of the tumor in such cases. Recent studies which have investigated the histological and immunohistochemical profile of these tumors showed, that ovarian tumors in most cases are secondary to the appendiceal tumors. In our case report we demonstrate that, despite of extensive immunohistochemical examinations (analysis of CK 7, 18, 20, CEA, HAM 56), it may be difficult to determine the histogenetic origin of pseudomyxoma peritonei.

Adenocarcinoma, Mucinous↗
PubMed2000

[Thrombosis of ovarian veins in puerperium associated with heparin-induced thrombocytopenia type II].

We report for the first time on a puerperal ovarian vein thrombophlebitis associated with heparin-induced thrombocytopenia type II. Two weeks after cesarean section with subsequent prophylactic application of heparin a thrombosis in the left deep femoral and pelvic veins and in the right ovarian vein occurred. Despite only moderately reduced platelet count a heparin-induced thrombocytopenia type II was diagnosed by heparin-induced platelet activation test. By treatment with plasmin activator lysis the thrombus was diminished. An operative procedure had been prevented. We conclude that also in cases with only moderately reduced platelet count during and after administration of heparin, especially in patients with wide spread and accumulating thrombosis, the presence of a heparin-induced thrombocytopenia should be taken into consideration. In contrast to difficulties in the management of puerperal ovarian vein thrombophlebitis--occurring independently from heparin-induced thrombocytopenia (surgical treatment necessary in most cases)--occurrence of puerperal ovarian vein thrombophlebitis in relation to heparin-induced thrombocytopenia seems to response better to fibrinolysis and anticoagulation.

Adult↗
PubMed2000

[Effect of menstrual cycle on Doppler measurements of adnexa tumors].

In a collective of 80 premenopausal women presenting with a total of 83 adnexal masses we tried to find out whether there is any influence on Doppler results by the phase of menstrual cycle. All measurements were performed with a 5.0 MHz transvaginal probe of an Acuson 125 Xp10 between April 1993 and September 1998. In 39 tumours measurements were performed during the follicular phase, in 44 tumours during the luteal phase. Histopathological evaluation showed 72 benign and 11 malignant adnexal masses. A cut-off of 0.69 for PI and 0.45 for RI was used to differentiate preoperatively between benign and malignant masses. In the follicular phase was a sensitivity of 40% and a specificity of 76.5% for RI. Referring values for PI were 60% and 70.6%. In the luteal phase RI led to a sensitivity of 83.3% and a specificity of 71.1%. Regarding PI a sensitivity of 100% and a specificity of 68.4% was achieved. There was no statistically significant difference when sensitivity and specificity for both parameters were compared in the two phases of menstrual cycle. These results are in contrast to the hypothesis that Corpora lutea are responsible for a higher degree of false positive results during the luteal phase. We therefore think that there is no advantage in performing Doppler measurements strictly during the follicular phase.

Adult↗
PubMed2000

[Comparative studies on the biological significance of the marker for proliferation Ki-67-Antigen and PCNA in primary ovarian carcinoma].

OBJECTIVE: It was shown in experimental and clinical investigations, that the biological behavior of malignant tumors is reflected by their proliferative activity. PCNA and Ki-67-Antigen are two nuclear antigens and considered to represent important markers of proliferation. We investigated their proliferation index in primary ovarian carcinomas and correlated the results with tumor stage, grading, histological type and survival. MATERIAL AND METHODS: The expression of PCNA and Ki-67-Antigen was immunohistochemically evaluated using the monoclonal antibodies MIB-1 and PC 10 on formalin-fixed, paraffin-embedded tissue of 49 patients. Statistical data were calculated by means of Fisher's Exact Test and Pearson's Chi 2 Test, survival was estimated by Kaplan Meier Curves. RESULTS: PCNA-expression was shown in all ovarian carcinomas and Ki-67-Antigen-expression was detected with one exception (98%) in all tumors, too. No correlation could be found between Ki-67-Antigen-expression and the prognostic factors mentioned above, whereas a high PCNA-expression was significantly correlated with the tumor grading (G3), (p < 0.05). Patients with ovarian carcinomas with high PCNA proliferation index showed the tendency of a shorter overall survival. DISCUSSION: Ki-67-Antigen and PCNA-expression could be detected in almost all primary ovarian carcinomas. PCNA compared to Ki-67-Antigen is considered to be more useful for the determination of the proliferative activity of ovarian carcinomas, although there was shown just a tendency of overall survival dependent on PCNA-expression, and there was a significant correlation only between PCNA-proliferation index and tumor grading.

Adult↗
PubMed2000

Analysis of the inter- and intravillous placental blood circulation in high-risk pregnancies before and after the hemodilution therapy using the colour-angio-mode.

OBJECTIVE: The aim of the study was to examine the efficiency of a hemodilution (HD) therapy on the inter- and intravillous placental blood circulation in high-risk pregnancies by applying the colour-angio-mode (CAM). PATIENTS AND METHODS: 24 patients were examined who had fetal growth retardation and/or pathological Doppler results. In all cases the hematocrit was >36%. The patients were given 500 ml Ringer solution and 500 ml HAES 10% intravenously per day; maternal heart rate and blood pressure were measured continuously. Prior to and after the therapy the same area of the placenta was examined using CAM; histograms demonstrating the distribution of the intensity values and summation values of the color pixels were calculated. RESULTS: In 14 patients the fetal outcome was good. The histograms showed in 11/14 cases an increase of low intensity values indicating an improvement of the placental circulation. The summation value of the color pixels as measured by CAM was significantly increased after the therapy in these cases (p = 0.022). In 10 patients the fetal outcome was unfavorable. The histograms showed a decrease of the intensity values in 6/10 cases. There was no significant change in the summation values of the color pixels after the therapy (p = 0.139). CONCLUSIONS: CAM sonography demonstrated for the first time a local effect of the HD therapy within the placenta. In the positive case the placental blood circulation will improve and the pregnancy develops favourably (responder). In the negative case there is no change of the placental blood circulation and pregnancy must be terminated due to a pathological fetal heart rate tracing, fetal growth failure or hypertensive disorders (nonresponder).

Adolescent↗
PubMed1999

The role of soluble adhesion molecules in evaluating endothelial cell activation in preeclampsia.

OBJECTIVE: Adhesion molecules, such as vascular cell adhesion molecule 1, are known to be increased in the serum of patients with preeclampsia, indicating that these molecules are possible markers of endothelial cell activation. We investigated the influence of serum from women with preeclampsia on the expression of adhesion molecules by cultured endothelial cells. STUDY DESIGN: Human umbilical vein endothelial cells were cultured in Ham/Iscove modified Dulbecco's medium containing 20% pooled human serum, l -glutamine (200 mmol/L), penicillin, and streptomycin. We stimulated these cells for 24 hours with sera from patients with preeclampsia and then determined the levels of vascular cell adhesion molecule 1, intercellular cell adhesion molecule 1, E-selectin, and P-selectin in the supernatant and in the maternal serum by means of enzyme-linked immunosorbent assay. These results were compared with those of sera obtained from normotensive pregnant and nonpregnant women. In addition, the expressions of these adhesion molecules on the endothelial surface were determined by immunofluo-rescence microscopy. RESULTS: Only for vascular cell adhesion molecule 1 and E-selectin were elevated plasma levels found in hypertensive patients, whereas intercellular cell adhesion molecule 1 and P-selectin showed similar plasma levels in all the patients. No differences in the levels of the adhesion molecules were found between the supernatants of endothelial cell cultures after stimulation with sera from patients with preeclampsia and those after stimulation with normotensive control sera. In contrast, with immunofluorescence microscopy we could detect higher amounts of vascular cell adhesion molecule 1, intercellular cell adhesion molecule 1, and E-selectin on the endothelial surface after stimulation with sera from women with preeclampsia. CONCLUSION: Although vascular cell adhesion molecule 1 and E-selectin were elevated in maternal serum samples from women with preeclampsia and on the endothelial surface after stimulation with such sera, there were no detectable increases in the levels of both of these adhesion molecules in the supernatant of cultured endothelial cells. We therefore assume that sera from women with preeclampsia may cause endothelial cell activation. Because we could not detect elevated concentrations of any of the investigated adhesion molecules in the supernatant of endothelial cells, we believe that factors other than sera from women with preeclampsia seem to play a major role in the release of soluble forms of adhesion molecules from the endothelial membrane.

Adult↗
PubMed1999

Collagenolysis in the lower uterine segment during parturition at term: correlations with stage of cervical dilatation and duration of labor.

OBJECTIVE: The objective of this study was to quantify the extent of neutrophil infiltration and the concentrations of enzymes involved in collagenolysis in the lower uterine segment in relation to the degree of cervical dilatation and the duration of labor. STUDY DESIGN: Biopsy specimens of the lower uterine segment were obtained from 62 women undergoing cesarean section at term. The number of extravascular neutrophils was assessed with enzyme histochemical evaluation, and the concentrations of matrix metalloproteinase-8, matrix metalloproteinase-9, and tissue inhibitor of metalloproteinases-1 by were assessed by enzyme-linked immunosorbent assay. RESULTS: The neutrophil count and the concentrations of matrix metalloproteinase-8, matrix metalloproteinase-9, and tissue inhibitor of metalloproteinases-1 increased with increasing cervical dilatation. At >6 cm the neutrophil count and the concentrations of matrix metalloproteinase-8, matrix metalloproteinase-9, and tissue inhibitor of metalloproteinases-1 were significantly higher than at <2 cm. An association with the duration of labor was found for the neutrophil count and the concentrations of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinases-1. Multiple linear regression analysis showed that the degree of cervical dilatation is more closely related to the 4 laboratory parameters investigated than to the duration of labor. CONCLUSION: The findings support the hypothesis that local changes (ie, collagenolysis) in the lower uterine segment unrelated to uterine activity play a crucial role in cervical dilatation at term.

Cervix Uteri↗
PubMed1999

Different placentation patterns in viable compared with nonviable tubal pregnancy suggest a divergent clinical management.

OBJECTIVE: In contrast to tubal abortions, viable ectopic pregnancies in color Doppler ultrasonography exhibit a signal-intensive ring around the gestational sac. We investigated the underlying differences in implantation and placentation. STUDY DESIGN: Histologic sections of fallopian tubes carrying viable tubal pregnancies (13 patients) and tubal pregnancies that aborted (8 patients) were immunostained for cytokeratin, MIB-1, CD-34, and CD-68. The data were studied by computer-aided image analysis followed by statistical evaluation (Student t test, P <.05). RESULTS: In contrast to tubal abortions, viable tubal pregnancies are characterized by implantation at the mesosalpingial rather than at the antimesosalpingial side of the organ. They exhibit deeper trophoblast invasion into the thickened tubal wall, more intense trophoblast proliferation (P <.001), and increased villous vascularization (P <.001). CONCLUSION: The morphologic findings correlate with preoperative Doppler ultrasonography. They suggest that trophoblast invasion, placental growth, and the fate of tubal pregnancies depend on the implantation site. They encourage a conservative management of anti-mesosalpingially implanted, nonviable ectopic pregnancies in clinically stable patients.

Antigens, CD↗
PubMed1999

Elevated soluble adhesion molecules in women with pre-eclampsia. Do cytokines like tumour necrosis factor-alpha and interleukin-1beta cause endothelial activation.

OBJECTIVE: The purpose of the present study was to evaluate the clinical significance of tumour necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) for endothelial cell activation in pre-eclampsia. Therefore, we determined and compared the correlations between these cytokines and circulating adhesion molecules in the sera of pre-eclamptic pregnant women, normotensive pregnant women and nonpregnant women. METHODS: The soluble adhesion molecules VCAM-1, ICAM-1, E-selectin, and P-selectin were determined in the serum of 38 pre-eclamptic pregnant women and 40 normotensive pregnant and nonpregnant controls using ELISA-techniques. We correlated these serum concentrations with the serum levels of TNF-alpha and IL-1beta, respectively, also determined by ELISA. RESULTS: Elevated serum levels of VCAM-1 and E-selectin could be detected in pre-eclamptic patients, with and without HELLP-syndrome. In contrast, no increased serum concentration of ICAM-1, P-selectin, TNF-alpha and IL-1beta were found in these patients. While significant correlation between VCAM-1 and E-selectin could be determined (r=0.604; p<0.001) no unambiguous correlations, however, were found between TNF-alpha or between IL-1beta and the examined adhesion molecules or the selectins. CONCLUSIONS: In contrast to in vitro investigations on cultured umbilical vein endothelium, our experimental results indicate that the cytokines TNF-alpha and IL-1beta can not explain endothelial cell activation, and that their measurement in serum is not useful for the detection of pre-eclampsia.

Adult↗
PubMed1999

Antenatal visualization of vascular anastomoses in monochorionic twins using color Doppler sonography: the protective function of these anastomoses and the phenomenon of interference beating.

This report concerns the antenatal visualization and velocimetry of an arterioarterial and a venovenous anastomosis in a monochorionic twin pregnancy using color Doppler sonography. The phenomenon of 'interference beating' occurs when two flow velocity waveforms are superimposed in one blood vessel. This characteristic image can be generated antenatally to confirm the existence of a vascular communication. We were able to reveal these anastomoses postnatally using the dye injection technique.

Adult↗
PubMed1999

Analysis of p53 mutation and cyclin D1 expression in breast tumors.

P53 and cyclin D1 are interacting regulatory genes and both are frequently altered in breast cancer. We analysed p53 mutation by SSCP and sequencing methods as well as p53 protein accumulation immunohistochemically in 34 consecutively operated breast tumors. None of 4 fibroadenomas revealed p53 mutation or p53 protein accumulation. Mutation of p53 was present in 7 carcinomas. Immunohistochemistry revealed accumulation of p53 protein in 6 carcinomas and there was a significant correlation between p53 mutation and protein accumulation. Overexpression of cyclin D1 protein was observed in 11 carcinomas by immunohistochemistry and no correlation was observed between cyclin D1 overexpression and p53 mutation or accumulation. Our data support the concept that the p53-cyclin D1 signal pathway and the cyclin D1 cascade are disregulated in breast cancer.

Breast Neoplasms↗
PubMed1999

Parturition at term: parallel increases in interleukin-8 and proteinase concentrations and neutrophil count in the lower uterine segment.

A relationship was sought between the tissue concentrations of interleukin (IL)-8, matrix metalloproteinase (MMP)-8 and MMP-9, and the numbers of the various leukocytes infiltrating the lower uterine segment stroma during parturition. Biopsy specimens of the lower uterine segment were obtained from 63 women undergoing Caesarean section at various stages of cervical dilatation at term. The concentrations of IL-8, MMP-8 and MMP-9 were determined with enzyme-linked immunosorbent assays, and the leukocytes were quantified immunohistochemically. The median IL-8 concentration (pg/mg total protein) rose significantly from 17.2 at < 2 cm dilatation, to 26.5 at 2 to < 4 cm dilatation, and 1954.0 at 4-6 cm dilatation, and remained at approximately this concentration at > 6 cm dilatation. The median MMP-8 concentration (ng/mg total protein) increased significantly from 32.2 at < 2 cm dilatation to 114.2 at > 6 cm dilatation. The median MMP-9 concentration (ng/mg total protein) rose significantly from 15.4 at < 2 cm dilatation to 102.1 at > 6 cm dilatation. The number of neutrophils was significantly higher at 4-6 cm and > 6 cm dilatation than at > 2 cm, reaching maximum values at > 6 cm dilatation. The findings in this study support the hypothesis that IL-8-induced infiltration of the cervical stroma by neutrophils and subsequent release of proteinases may play a key role in parturition.

Adult↗
PubMed1999

Consensus polymerase chain reaction and enzyme-linked immunosorbent assay for human papillomavirus detection and typing in cervical specimens.

Human papillomavirus (HPV) infection is common in cervical intraepithelial neoplasia (CIN). This study investigates HPV detection and typing assay based on polymerase chain reaction amplification of L1 open reading frame with general primers GP5/GP6, followed by enzyme-linked immunosorbent assay detection with type-specific DNA probes. To determine the sensitivity of this assay, formalin-fixed CaSki cells were used as reference cell lines. Fifty copies of viral DNA diluted in DNA from 100,000 noninfected cells could be detected. This assay was also investigated for HPV detection and typing of 67 cervical specimens diagnosed with with CIN III or carcinoma in situ (CIS) and their adjacent squamous epithelium. The CIN III lesions were infected in approximately 80% of the samples, 81% in the neighboring CIN II, and 68% in CIN I. The HPV infection was even detectable in 54% of nondysplastic epithelium located near a CIN III lesion.

Base Sequence↗