Biomedical subjects

Werner Rath

Publications and source records attributed to Werner Rath.

32 records · Page 2Linked to original sources

PubMed2003

GLUT1 messenger RNA and protein induction relates to the malignant transformation of cervical cancer.

We studied whether induction of glucose transporters (GLUTs) 1 to 4 correlates with human papillomavirus (HPV)-dependent malignant transformation of cervical epithelium. Tissue samples of cervical intraepithelial neoplasia (CIN; grades 1 to 3), invasive carcinomas, and lymph node metastasis were examined. HPV typing was performed. Tissue sections were immunostained with GLUT1 to GLUT4 antibodies. Messenger RNA (mRNA) in situ hybridization confirmed GLUT1 protein expression. Weak expression of GLUT1 was found in nondysplastic HPV-positive and HPV-negative epithelium; significant expression was observed in preneoplastic lesions, correlating with the degree of dysplasia. In CIN 3 high-risk HPV lesions, cervical cancer, and metastasis, GLUT1 was expressed at highest levels with a strong correlation of GLUT1 mRNA and protein expression. Immunostains for GLUT2 to GLUT4 were negative. Cervical tumor cells respond to enhanced glucose utilization by up-regulation of GLUT1. The strong induction of GLUT1 mRNA and protein in HPV-positive CIN 3 lesions suggests GLUT1 overexpression as an early event in cervical neoplasia. GLUT1 is potentially relevant as a diagnostic tool and glucose metabolism as a therapeutic target in cervical cancer.

Cell Transformation, Neoplastic↗

PubMed2002

A whole blood flow cytometric determination of platelet activation by unfractionated and low molecular weight heparin in vitro.

The influence of unfractionated (Heparin-Natrium) and low-molecular heparin (Fragmin(R)) on platelet activation in whole blood was investigated by FACS analysis in vitro using antibodies against glycoprotein (gp) IIb/IIIa (CD 41), GMP 140 (CD 62P), gp 53 (CD 63) and fibrinogen. Samples were also labeled with anti-gp Ib (CD 42b). Neither unfractionated heparin (UFH) nor low molecular weight heparin (LMWH) led to significant (i.e., p<0.05) changes in fluorescence intensities of platelets labeled with anti-gp IIb/IIIa or anti-gp 53. Significant platelet activation due to unfractionated heparin could be observed by labeling with anti-GMP 140 (UFH: p=0.009; LMWH: p=0.16). The proportion of platelets with surface-bound fibrinogen was significantly increased (UFH: p=0.00006; LMWH: p=0.008). After incubation with heparins, activation ability of platelets by adenosine diphosphate (ADP) was significantly increased. The potentiating action of unfractionated heparin was larger. Therefore, flow cytometric results of platelet activation in patients receiving heparin should be interpreted carefully.

Adenosine Diphosphate↗

PubMed2002

Messenger ribonucleic acid levels of interleukin-1 beta, interleukin-6 and interleukin-8 in the lower uterine segment increased significantly at final cervical dilatation during term parturition, while those of tumor necrosis factor alpha remained unchanged.

OBJECTIVE: To investigate the content of tumor necrosis factor alpha, interleukin-1 beta, interleukin-6 and interleukin-8 messenger ribonucleic acid (mRNA) in the lower uterine segment during term parturition. STUDY DESIGN: mRNA extracts from the lower uterine segment obtained from 53 women undergoing non-elective caesarean section at term were analyzed by semi-quantitative reverse transcriptase polymerase chain reaction. The patients were grouped according to cervical dilatation (less than 2 cm, n=18; 2 to less than 4 cm, n=13; 4-6 cm, n=7; more than 6 cm, n=15) at the time of caesarean section. RESULTS: Interleukin-1 beta and interleukin-8 mRNA-contents at more than 6 cm cervical dilation were significantly higher than at less than 2 cm. The levels of interleukin-6 were already significantly increased in the 4-6 cm group, while the tumor necrosis factor alpha ribonucleic acid content did not change during parturition. CONCLUSION: The process of cervical dilatation during parturition at term is associated with an increased expression of interleukin-1 beta, interleukin-6 and interleukin-8 mRNA in the lower uterine segment. These findings support the theory that the activation of the inflammatory network plays an important role in the progress of cervical dilatation.

Cervix Uteri↗

PubMed2002

Invasive depth of extravillous trophoblast correlates with cellular phenotype: a comparison of intra- and extrauterine implantation sites.

During intrauterine human placentation, extravillous trophoblast invades uterine tissues starting with proliferating stem cells at the basement membrane of anchoring villi. Transition to the postproliferative invasive phenotype takes place several cell layers distant. Here we show that in intrauterine pregnancies invasive trophoblast comprises three cellular phenotypes: a. Small spindle-shaped trophoblast cells are found along the whole invasive pathway throughout pregnancy. They are embedded in little heterogeneous extracellular matrix but expose only fibronectin receptors (integrins alpha5beta1, alphavbeta3/5), resulting in a partial integrin-matrix mismatch. b. Large polygonal trophoblast cells are rare in early pregnancy but increase in number towards term. They secrete ample heterogeneous extracellular matrix and expose integrins specifically matching the opposing matrix molecules (integrins alpha6beta4, alpha5beta1). c. Multinucleated giant cells in all stages of pregnancy form a kind of peripheral shell of trophoblast. In contrast to intrauterine pregnancies, in viable tubal pregnancies, Mib-1 expression indicating proliferation, extends deeply into the invasive pathway. Trophoblast cells of the invasive pathway mostly belong to the small spindle-shaped phenotype and secrete little extracellular matrix, mainly fibronectins. At the transition to the second cellular layer of cell columns expression of integrin alpha6beta4 switches to expression of alpha5beta1 and alphavbeta3/5. Viable tubal pregnancies are characterised by a broad overlap of proliferative with invasive phenotype as well as a general integrin-matrix mismatch. The differences in proliferation patterns, cellular phenotype and matrix-integrin co-localisation may well explain the increase of invasiveness of normal extravillous trophoblast from term intrauterine via early intrauterine to viable tubal pregnancies.

Cell Count↗

PubMed2002

Quantitation and localization of inflammatory cytokines interleukin-6 and interleukin-8 in the lower uterine segment during cervical dilatation.

PURPOSE: Cervical dilatation during parturition is associated with a significant increase of interleukin (IL)-6 and IL-8. The purpose of this study was to localize the respective messenger RNA and to quantitate their protein levels during various stages of dilatation. METHODS: Protein extracts from 34 biopsy specimens of the lower uterine segment at various stages of cervical dilatation (<2, 2 to <4, 4-6, and >6 cm) were subjected to enzyme linked immunosorbent assay for IL-6 and IL-8 to document their concentration. The respective mRNA expression was studied using reverse transcriptase PCR using IL-6 and IL-8 specific primers. Localization of IL-6 and IL-8 was done by in situ hybridization using biotinylated probes. RESULTS: The IL-6 and IL-8 concentrations increased significantly in the lower uterine segment tissues at 4-6 cm of dilatation. Expression of IL-8 was seen in all the tissues at or more than 4 cm dilatation, whereas IL-6 expression was inconsistent. In situ hybridization localized IL-6 and IL-8 mRNA to the glandular epithelium. CONCLUSIONS: The increase in the inflammatory cytokines (IL-6 and IL-8) during parturition is associated with cervical effacement.

Biopsy↗

PubMed2002

Cytokine concentrations in the amniotic fluid during parturition at term: correlation to lower uterine segment values and to labor.

BACKGROUND: In previous studies a significant increase in interleukin (IL)-6 and IL-8 concentrations in the lower uterine segment parallel to cervical dilatation at term could be found, however only a weak correlation to duration of labor was detected. This study compares amniotic fluid concentrations of interleukin (IL)-6 and IL-8 with those in the lower uterine segment, and the duration of labor. METHODS: Amniotic fluid and lower uterine segment specimens were obtained from 29 patients during cesarean section at term. The patients were divided into groups according to cervical dilatation (< 2 cm, 2-3.9 cm, 4-6 cm, > 6 cm) and to labor (0 h, > 0-12 h, > 12 h). Interleukin-6 and IL-8 concentrations were determined by enzyme immunoassay. RESULTS: Amniotic fluid IL-6 already increased at 2-3.9 cm (p = 0.02), while the steepest increase in IL-8 was observed at > 6 cm (p = 0.003). No correlation with lower uterine segment values was observed for either of the cytokines. However, the amniotic fluid IL-6 concentration correlated with labor (p = 0.0008). CONCLUSION: The increase in the concentration of IL-6 in the amniotic fluid earlier than its increase in the lower uterine segment supports the hypothesis that IL-6 plays a crucial role for the promotion of labor in the first place, and afterwards for the biochemical degradation processes in the lower uterine segment. The fact that the greatest increase in IL-8 concentration occurs only at > 6 cm indicates that this chemotactic cytokine has only minor significance in the initiation of parturition by its concentration in the amniotic fluid.

Amniotic Fluid↗

PubMed2002

Long-term follow-up and prognostic significance of angiogenic basic fibroblast growth factor (bFGF) expression in patients with breast cancer.

The development of distant metastasis in breast cancer patients is the key step towards worse prognosis. The angiogenic basic fibroblast growth factor (bFGF) has been associated with tumorigenesis and metastasis in several human cancers. Therefore, bFGF expression was studied by immunohistochemistry in 111 patients with primary breast cancer. The results were correlated with prognostically relevant clinico-pathological features. such as tumor stage, grading. nodal stage and survival. bFGF was expressed in approximately 70% of the breast cancer tissues; 30% of the tumors showed strongly positive staining. With the exception of histological grading (p < 0.05), no correlation was found between the extent of bFGF expression and prognostic parameters. Analysis of survival showed a significantly (p < 0.05) prolonged survival for patients with a concomitant absence of axillary lymph node metastasis and bFGF immunoreactivity. Our data suggest that increased bFGF expression is a novel parameter for worse prognosis in nodal-negative breast cancer patients.

Aged↗

PubMed2002

Chorioamnionitis: elevated interleukin-6 and interleukin-8 concentrations in the lower uterine segment.

AIMS: To determine interleukin (IL)-6 and IL-8 concentrations in the lower uterine segment in patients with chorioamnionitis compared to those without. METHODS: Biopsy specimens from the lower uterine segment of 33 patients with chorioamnionitis were matched to specimens of 33 patients without. The biopsies had been taken during cesarean section. The concentrations of IL-6 and IL-8 in protein extracts of these specimens were determined by enzyme linked immunosorbent assays. RESULTS: Compared to the controls patients with chorioamnionitis showed significantly lower gestational age and higher parity, and were more likely to receive fenoterol or betamethasone. In the chorioamnionitis group the median IL-6 concentrations were higher than in the controls (61.5 and 19.4 pg/mg protein, respectively [p < 0.01]). The same applies to the median IL-8 concentrations (162.3 and 13.4 pg/mg protein, respectively [p < 0.001]). CONCLUSIONS: To our knowledge this is the first study which could clearly demonstrate significantly increased IL-6 and IL-8 levels in the lower uterine segment of patients with chorioamnionitis. Increased concentrations of pro-inflammatory cytokines may play a pivotal role in cervical softening and dilatation during chorioamniotic infection.

Adult↗

PubMed2002

Anal sphincter injury during vaginal delivery--an argument for cesarean section on request?

AIMS: Fear of damage to the pelvic floor from vaginal delivery and long-term sequelae (urinary and anal incontinence) sometimes being cited as an indication for cesarean section on request. The aim of the present study was to compare the effects of vaginal delivery versus elective cesarean section on anal sphincter function. MATERIAL AND METHODS: We studied 71 consecutive women six weeks before delivery, 52 of them 4-6 weeks after delivery, and all patients with occult sphincter lesions 3 months after delivery. A bowel function questionnaire was completed, and anal endosonography, manometry, and measurement of the pudendal-nerve terminal motor latency were performed. RESULTS: Forty-two (80.8 percent) patients were delivered vaginally, ten (19.2 percent) by elective cesarean section at term. Clinically recognized anal sphincter injuries occurred in 9.5 percent (4) of patients, two of them developed incontinence for gas. The overall incidence of anal incontinence after vaginal delivery was 4.8 percent. Occult sphincter defects were identified endosonographically in 19 percent (8) of women, there was no reported case of any anal incontinence 3 months after delivery. No woman delivered by cesarean section had altered anal continence or any significant change in anal pressures, rectal sensibility, and PNTML. CONCLUSION: Severe sphincter tear is the single most important factor leading to anal incontinence in women, whereas occult sphincter defects are rarely associated with short-term sequelae, but may predispose to the development of anal incontinence later on in life. Elective cesarean section should be recommended for women at increased risk for anal incontinence.

Adult↗

PubMedDate not supplied

[Psychic disturbances in the postpartum period: an increasing problem?].

Postpartum psychic disorders can be mainly divided into 3 groups: The so-called postpartum blues, the postpartum depression and the postpartum psychosis. The postpartum blues occurs 3 - 5 days postpartum in 50 - 70 % of deliveries mostly disappearing after one week without specific therapy. However, 20 - 30 % of patients will develop a depression in their further postpartum course so that a thorough evaluation concerning depression is warranted, if blues symptoms persist more than 2 weeks. Postpartum depression can be found in 10 - 15 % of deliveries and mostly occurs several weeks or months after delivery with symptoms of depressive mood, sleeping disorders, anxiety, loss of interest and accord and feelings of guilt up to suicidal ideas. In order not to misinterpret them as postpartum blues specific questions concerning the mood of the young mother during the postpartum examination - if necessary using the Edinburgh scale - are recommended. In patients with known risk factors for a postpartum depression (i. e. postpartum depression or psychosis in previous pregnancies, depression disorder, anxiety disorder, bipolar illness), a thorough survey is mandatory and - if necessary - a prophylactic treatment in cooperation with the psychiatrist. Less severe forms of postpartum depression can mostly be treated with psychotherapy and sociotherapy on an outpatient basis. In more severe cases, antidepressant drugs (selective serotonin reuptake inhibitors, SSRIs or some tricyclic drugs) are indicated. Postpartum anxiety and compulsive disorders respond well to psychotherapy; besides in anxiety disorders benzodiazepines are recommended, in compulsive disorders SSRIs. Postpartum psychoses (about 0.1 - 0.2 %) most often occur in bipolar or schizoaffective disorders or after postpartum psychosis. They require a hopitalization mainly because of the danger of suicide and homicide toward the newborn; ideally this is performed in mother-child-units.

Adult↗

PubMedDate not supplied

Importance of ductus venosus Doppler assessment for fetal outcome in cases of intrauterine growth restriction.

OBJECTIVE: The measurement and evaluation of ductus venosus (DV) blood flow velocity waveform in high-risk pregnancies has been studied intensively in recent years in order to find a more intermediate signal of fetal compromise. Our objective was to study the fetal outcome of pregnancies with intrauterine growth retardation (IUGR) and normal pulsatility of DV compared to an IUGR group with increased DV pulsatility. METHODS: The outcome of 42 fetuses before 32 weeks of gestational age without chromosomal or structural aberrations was analyzed. All fetuses showed IUGR <5th percentile based on placental insufficiency diagnosed by pathologic RI >90th percentile of both maternal uterine arteries. One group (30 fetuses; mean weight 730 g/SD 190 g; mean gestational age 197 days/SD 12 days) showed normal, the other (12 fetuses, mean weight 675 g/SD 179 g; mean gestational age 198 days/SD 12 days) reduced, but neither absent nor reverse DV flow during atrial contraction. All 42 fetuses were delivered by cesarean section because of severe variable or prolonged decelerations. We measured blood flow velocities of the DV in every fetus on an average 3.7 days (range 1-5 days) before cesarean section. Fetal outcome was determined by Apgar scores after 5 and 10 min, arterial pH and base excess; neonatal morbidity was recorded by intensive follow-up. RESULTS: There were no significant differences of pH, umbilical artery base excess, Apgar scores and severe neonatal complications between the two groups. CONCLUSIONS: Our own data show no correlation between increased pulsatility in the DV (without absent or reverse flow during atrial contraction) and fetal outcome before 32 gestational weeks, even in cases of severe growth restriction based on placental insufficiency. Therefore in these cases reduced DV flow during atrial contraction should cautiously be interpreted regarding obstetrical decisions.

Blood Flow Velocity↗

PubMedDate not supplied

Estrogen receptor alpha and progesterone receptor A and B concentration and localization in the lower uterine segment in term parturition.

OBJECTIVE: To determine the localization and concentrations of estrogen receptor alpha and progesterone receptors A and B in the lower uterine segment during term parturition. METHODS: Biopsies were taken from 70 patients during nonelective cesarean delivery. The patients were at different stages of cervical dilatation (<2 cm, 2-3.9 cm, 4-6 cm, >6 cm) and different duration of labor (< or =6 hours, >6-12 hours, >12 hours). The receptor concentrations were determined with solid phase immunoassays, and their localization was investigated immunohistochemically. RESULTS: Estrogen receptor alpha concentration decreased significantly from 2.12 fmol/mg protein at less than 2 cm dilatation to 1.08 fmol/mg (4-6 cm) but tended to increase at greater than 6 cm. Progesterone receptor A and B concentration was 84.7 fmol/mg at less than 2 cm dilatation, decreased significantly to 36.6 fmol/mg (2-3.9 cm), and increased again with further dilation. Concentrations of both receptors did not depend on duration of labor. By immunohistochemistry only progesterone receptor A and B was found to be expressed by endothelial and smooth muscle cells of the vessels, stromal fibroblasts, smooth muscle cells in the myometrium, and glandular epithelial cells. Regardless of the extent of cervical dilatation, expression of progesterone receptors A and B was marked. CONCLUSION: A decrease in estrogen receptor alpha and progesterone receptor A and B concentration in the early phase of first stage labor may play a role in cervical dilation at term.

Estrogen Receptor alpha↗

PubMedDate not supplied

The value of positron emission tomography in the follow-up for breast cancer.

BACKGROUND: The aim of this study was to investigate the diagnostic value of FDG PET in the follow-up for breast cancer in disease-free patients and patients suspected of having recurrent or metastatic disease. As a single imaging tool, PET can be compared with the conventional diagnostic means used for different examination sites. PATIENTS AND METHODS: A total of 73 PET studies were carried out on 57 patients who had been diagnosed as having breast cancer. Sixteen patients had two PET scans. Thirty-eight scans (52.%) were performed in a follow-up setting. Thirty-five PET scans were performed in patients suspected of having recurrent disease or elevated tumor marker. Depending on the region of suspicion, conventional imaging included computed tomography, magnetic resonance imaging, chest X-ray, ultrasound and X-ray. All the patients in our study were followed-up for a period of 12 months. RESULTS: PET correctly identified metastatic or recurrent disease in 25 out 27 cases of clinical suspicion. In patients examined because of elevated tumour marker CA 15-3, PET was able to detect recurrence or metastatic disease in six of the eight patients. The absence of disease was correctly diagnosed by PET in 35 out of 38 scans in 24 patients in the follow-up for breast cancer. The overall sensitivity and specificity for PET was 80.6% and 97.6%, respectively. On the basis of a yearly rate of disease progression of 5-8%, the mean positive predictive value was 74.5% and the mean negative predictive value 98.3%. CONCLUSION: PET has been shown to have impact on the staging and management of recurrent or metastatic breast cancer in cases of suspicion and in a follow-up setting. The current oncological situation can be clarified with a single basic imaging modality.

Abdominal Neoplasms↗

PubMedDate not supplied

Diffuse growth pattern affects E-cadherin expression in invasive breast cancer.

We investigated the correlations between growth patterns and E-cadherin expression by immunohistochemistry and the presence of mutations of exons 6-10 of the E-cadherin gene by PCR-SSCP, in 79 cases of invasive lobular and ductal breast cancer. E-cadherin expression showed a tendency to be lower in lobular than in ductal carcinomas (p=0.064). In 60% of lobular carcinomas the diffuse growth pattern and in 72% of ductal carcinomas the compact growth pattern predominated. E-cadherin expression was significantly lower in diffuse than in compact tumor area (p<0.001) and not related to carcinoma type when it was considered in tumor areas with either diffuse (p=0.278) or compact (p=0.128) growth pattern. No mutations were detected. In conclusion, loss of E-cadherin expression is related to an increase of diffuse growth pattern in both lobular and ductal types of breast cancer, and the differential proportions of growth patterns in both tumor types cause the tendency for lower E-cadherin expression in the lobular type.

Adult↗