R. Osmers

ORIGIN OF CERVICAL COLLAGENASE DURING PARTURITION

Cervical biopsy specimens were obtained under standard conditions from the posterior lip of the uterine cervix in 105 patients. A significant increase of collagenase activity was observed during parturition as determined with an assay with iodine 125-labeled native triple-helical collagen type I as the substrate. The collagenase was not likely to originate from cervical fibroblasts because in situ hybridization failed to detect synthesis of the specific procollagenase messenger ribonucleic acid. However, migration of polymorphonuclear leukocytes into the cervical stroma occurred on onset of labor, and an antibody specific for human leukocyte collagenase that did not cross react with fibroblast collagenase revealed the presence of the enzyme in the granules of polymorphonuclear leukocytes and subsequently in the extracellular matrix of the cervix. Therefore it is likely that the cells critically involved in collagen degradation during cervical dilatation are not resident fibroblasts but rather polymorphonuclear leukocytes emigrating from blood vessels.

Biochemical changes in human cervical connective tissue after intracervical application of prostaglandin E2.

Cervical biopsies were taken during the first trimester from primigravidae and plurigravidae at different time points after intracervical application of prostaglandin E2-gel. Collagenase activity was determined by a highly specific technique using native, triple helical collagen as substrate. Elastase-alpha 1-proteinase-inhibitor complex (elastase) was measured by a commercially available assay, and glycosaminoglycan (GAG) analyses were performed as described by Greiling et al. (5, 6). The maximum activity of collagenase was found 2 hours after PGE2 application in plurigravidae and 4 hours after application in primigravidae. Elastase activity rose nearly 7-fold to maximum values 4 hours after PGE2 application. The total GAG concentrations and the dermatan sulfate concentrations increased by approximately 10%, while the hyaluronic acid concentrations were found to be elevated significantly by nearly 50% in the PGE2-primed cervices. We conclude that a time-dependent enzymatic collagen degradation by collagenases and other proteinases and an increase in hyaluronic acid concentrations are the significant biochemical events underlying PG-induced cervical ripening.

Prediction of fetal Rh D and Rh CcEe phenotype from maternal plasma with real-time polymerase chain reaction

Real-time PCR methods for the detection of RHD and the C, c, and E allele of RHCE were applied for the prediction of fetal Rh phenotype using maternal plasma. In one of 36 samples investigated the DNA extraction failed. When we tested the remaining 35 samples for Rh antigens which were absent on the mothers red cells, the fetal D-status was correctly determined in 26 of 27 cases (1 false negative). Fetal C was tested correctly in 23 samples, c was true positive in the only c-negative woman and the fetal E-status was correctly determined in 35 cases. In conclusion real-time PCR of maternal plasma is a non-invasive method to determine fetal RH genotype. However, more studies are required for routine applications because the method is not 100% sensitive.

Preoperative evaluation of ovarian tumors in the premenopause by transvaginosonography

OBJECTIVE The aim of the study was to establish reproducible sonomorphologic criteria by use of transvaginosonography in the preoperative evaluation of ovarian tumors in the premenopause. STUDY DESIGN In a prospective study from 1987 to 1993 we investigated 1072 ovarian tumors. All tumors > or = 3 cm were included in the study. To avoid unnecessary operations, all tumors we rescanned after 6 weeks. The sonomorphologic criteria were correlated with the histologic findings. RESULTS A total of 4.3% of ovarian tumors in the premenopause were malignant. In the special group of sonographically simple ovarian cysts we found 0.8% malignancies. The incorporation of a control scan after 6 weeks in the management of ovarian cysts reduces the number of unnecessary operations on functional cysts. Only 5.5% of the functional tumors were operated on. The risk for malignancy in cystic-solid ovarian tumors is 17.0%, the highest of all sonomorphologic tumor types. CONCLUSIONS The use of reproducible sonomorphologic criteria in combination with a control scan in premenopausal women with ovarian cysts proved to be efficient to reduce the number of unnecessary operations and to evaluate the risk for malignancy.

Activated protein C resistance and Factor V Leiden in patients with hemolysis, elevated liver enzymes, low platelets syndrome ☆

Objective Hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome is characterized by a distinct activation of the coagulation system. A mutation of the gene coding for coagulation Factor V (Factor V Leiden) has been identified as the most frequent risk factor for thrombosis. To identify risk factors for HELLP syndrome, we determined coagulation parameters and the Factor V Leiden mutation in women who previously had developed HELLP syndrome. Methods Coagulation parameters (activated protein C resistance, antithrombin, protein C, protein S) were determined in 21 women 6 months to 9 years after they had developed HELLP syndrome in the third trimester. In addition, these women were analyzed for the presence of the Factor V Leiden mutation. Results Of these analyzed women, 33% (seven of 21) had an activated protein C resistance (activated protein C ratio less than 2.0). Another 38% of the women had subnormal activated protein C ratios (2.0-2.3). Only 57% of the women with an activated protein C resistance were identified as heterozygous carriers of the Factor V Leiden mutation (four of seven). Conclusion Women with HELLP syndrome have a higher incidence of Factor V Leiden mutations. This increased incidence does not, however, account fully for the increased frequency of activated protein C resistance in these patients.

Visualization of Blood Flow in Small Ovarian Tumor Vessels by Transvaginal Color Doppler Sonography after Echo Enhancement with Injection of Levovist

The echo-enhancing effect of an ultrasound contrast medium (Levovist) in color Doppler sonography of small vessels in ovarian tumors was studied in a group of 30 women. The vascularity of adnexal masses with a suspicion of primary carcinoma in 3 and benign lesions in 27 cases was investigated before and after injection of 300 mg/ml of Levovist. In 17 cases color flow mapping showed increased vascularity either in the cystic wall or in solid structures within the tumor. In all patients we observed enhancement of Doppler signal intensity. Our results show that Levovist facilitates waveform analysis in very small vessels with poor velocity patterns.

Evaluation of ovarian tumors in postmenopausal women by transvaginal sonography

OBJECTIVE The aim of the present study was the evaluation of simple reproducible sonomorphological criteria for the preoperative evaluation of ovarian tumors in postmenopausal women by use of transvaginal sonography. STUDY DESIGN Postmenopausal women (> or =1 year of secondary amenorrhea) with ovarian tumors (n=378; tumors > or =3 cm and <3 cm but with solid parts) were examined in a prospective study by transvaginal sonography prior to surgery between 1987 and 1993. The sonomorphological criteria were correlated with the histological findings of the tumors. RESULTS Of all ovarian tumors in postmenopausal women, 6.3% were functional cysts (follicular or corpus luteum cysts). Almost all of them were detected within the first 5 years of postmenopause. The other ovarian tumors were diagnosed as retention cysts (17.5%), benign neoplasms (39.4%), and malignant tumors (36.8%). Simple ovarian cysts (monolocular, smooth inner wall) represented sonomorphologically the second most frequent type of ovarian tumors in postmenopausal women (35.7%). Of these tumors, 9.6% were diagnosed as malignant. CONCLUSIONS Simple reproducible sonomorphological criteria proved to be a useful clinical parameter in the preoperative evaluation of ovarian tumors.

Collagenase activity in the cervix of non-pregnant and pregnant women.

SummaryCervical biopsies were obtained from non pregnant patients and from pregnant at various stages of gestation and during labour. The tissues were extract with a Ca++-containing buffer, and collagenase activity was determined in these extracts using a solid phase assay in which triple helical125I-labelled collagen was cleaved. Collagenase was detected in all samples but significantly elevated activity was only present in labour at 6–8 cm cervical dilatation. This provides direct evidence for the crucial role of specific collagen degradation during cervical ripening and dilatation.

Efficacy of black cohosh (Cimicifuga racemosa) medicines for treatment of menopausal symptoms – comments on major statements of the Cochrane Collaboration report 2012 “black cohosh (Cimicifuga spp.) for menopausal symptoms (review)”

Abstract Menopausal symptoms management with high-quality plant extracts from Actaea (Cimicifuga. racemosa rootstock is well-established. Efficacy and safety are supported by research and clinical trials since several decades and backed up by official monographs. However, the recent published Cochrane review on black cohosh neglects major evidence for beneficial effects. The authors’ negative conclusions are questionable and call for reply and clarification. Our careful reconsideration of all appropriate placebo-controlled clinical studies reveals a standardized mean difference of 0.385 in favor of black cohosh (p < 0.0001).

Increased serum levels of hyaluronic acid in pregnancies complicated by preeclampsia or hemolysis, elevated liver enzymes, and low platelets syndrome.

OBJECTIVE Fifteen percent of patients who later have hemolysis, elevated liver enzymes, and low platelets syndrome develop initially have nonspecific symptoms. Early diagnosis could ensure adequate obstetric management; however, prognostic biochemical tests are lacking. We hypothesized that elevated hyaluronic acid serum levels might be an early indicator of hemolysis, elevated liver enzymes, and low platelets syndrome because it is known to be a sensitive marker of liver cell function. STUDY DESIGN Hyaluronic acid in serum was measured in patients with normal pregnancies (n = 109) and in those patients with pregnancies complicated by preeclampsia (n = 14) or hemolysis, elevated liver enzymes, and low platelets syndrome (n = 11). RESULTS A significant increase in hyaluronic acid serum concentrations was observed in patients with hemolysis, elevated liver enzymes, and low platelets syndrome or with preeclampsia (p < 0.05). The extent of hyaluronic acid serum levels in hemolysis, elevated liver enzymes, and low platelets syndrome correlated with the clinical severity of the individual course of disease as measured by intensive care unit time (r = 0.72; p < 0.02). CONCLUSIONS Serum levels of hyaluronic acid in preeclampsia and hemolysis, elevated liver enzymes, and low platelets syndrome are significantly elevated and might play an important diagnostic and prognostic role in patients with hemolysis, elevated liver enzymes, and low platelets syndrome.