W. Rath

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.

Elevated serum levels of a c-erbB-2 oncogene product in ovarian cancer patients and in pregnancy

Amplification of the proto-oncogene c-erbB-2 (HER-2/neu) has been shown to be a prognostic marker in ovarian cancer. In order to obtain further information on the biological role of the c-erbB-2 gene product p185 it is necessary to quantify expression levels. In this study we evaluated an enzyme-linked immunosorbant assay (ELISA) for the extracellular domain of p185 to determine whether a soluble oncoprotein fragment can be detected in the serum of ovarian cancer patients and in the serum of pregnant women. Sera from 199 women (57 previously untreated ovarian cancer patients, 62 pregnant women and 80 healthy controls) were assaved in a sandwich ELISA utilizing two mouse monoclonal antibodies. To study c-erbB-2 overexpression in ovarian cancer tissue samples we have used an immunohistochemical technique involving a monoclonal antibody specifically reactive with the external domain of the protein p185. The mean serum value for the normal controls was 1203 HNU/ml with a standard deviation (SD) or 279 HNU/ml and a range of 595–1947 HNU/ml. We chose a level of 1761 HNU/ml (2 SD above the mean) as a cut-off to distinguish individuals with elevated levels. The ovarian cancer patients serum values ranged from 526 to 16 332 HNU/ml. Immunohistochemically detectable p185 was noted in 8 of 57 ovarian cancer patients. The oncoprotein fragment levels in the sera from these 8 patients ranged from 878 to 16 332 HNU/ml. Of 8 patients with p185 overexpression in their tumors, 4 had elevated serum levels. In the sera from the 49 cancer patients without overexpression the values were distributed in the range 526–2892 HNU/ml. There was no association between serum oncoprotein fragment levels and tumor stage, histological type or grading. Serum concentrations of the p185 fragment in pregnancy ranged from 612 to 3265 HNU/ml. The highest levels were found in the third trimester. The results of the present study raise the possibility that the soluble c-erbB-2 protein level in serum is an indicator for cell proliferation and therefore deserves further evaluation as a diagnostic tool in ovarian cancer patients and pregnancy.

Haptoglobin as a sensitive marker of hemolysis in HELLP-syndrome.

In a prospective study we measured laboratory variables of hemolysis in 25 patients with HELLP‐syndrome. Reduced haptoglobin levels were observed in all 25 patients at diagnosis. Elevated bilirubin and plasma hemoglobin levels were observed in 5/25 patients while an abnormal peripheral blood smear was found in 11/25 patients. Our results suggest that haptoglobin is a sensitive parameter for early detection of moderate hemolysis in HELLP‐syndrome and should be included in laboratory screening to aid diagnosis.

Histological and electron-microscopic examinations of collagenous connective tissue of the non-pregnant cervix, the pregnant cervix, and the pregnant prostaglandin-treated cervix

SummaryThe histological appearance of the prostaglandin-pretreated cervix of early pregnancy (8–13 weeks) showed the changes found in the pregnant cervix at term. Electron microscopy showed collagen fibrils of normal periodicity (640 Å) and also collagen degradation products. Evidence of splitting of collagen fibrils could only be seen with light microscopy.

The importance of early laboratory screening methods for maternal and fetal outcome in cases of HELLP syndrome

Over a period of 5 years and 3 months 50 patients with HELLP syndrome were treated at our hospitals. All of these patients fulfilled the criteria of this syndrome described by Weinstein. Pre-eclampsia with HELLP syndrome was either diagnosed correctly by the referring doctor or on admission by the obstetrician on the basis of the laboratory findings. The median time interval between admission and delivery was 3 hours (range: 0.5-40 hours). In 49 patients, Caesarean section was performed, one patient developed a HELLP syndrome 18 hours after vaginal delivery. The median gestational age at delivery was 35 weeks (range: 26-40). Only three of 51 infants died before delivery, and there was one neonatal death, resulting in a perinatal mortality of 7.8%. Apgar scores below 7 occurred in 15 of the newborns after 1 min and in only 2 after 5 min. In 47 cases, Caesarean section and hospital course were free of complications; in three patients postoperative hemorrhages required relaparotomy, in two of these patients puerperal hysterectomy had to be performed. In our experience, the relevant laboratory parameters should be determined in any pregnant women with right upper quadrant pain independent of the severity of pre-eclampsia in order to diagnose HELLP syndrome as soon as possible. Both early control and follow-up of the laboratory parameters and immediate delivery--by Caesarean section, if necessary--may lead to a reduction of maternal mortality and morbidity and to an improvement of perinatal results.

Collagen degradation in the pregnant human cervix at term and after prostaglandin-induced cervical ripening

SummaryThe role of enzymatic collagen degradation in prostaglandin-induced and physiological cervical ripening was studied by determining collagenase and other proteolytic activity in extracts of cervical biopsies. Collagenase activity was assayed in a highly specific and sensitive system using native collagen type I as substrate. The intracervical application of sulprostone gel prior to termination of 1st trimester pregnancy led to a marked improvement in cervical dilatability. Collagenase and proteolytic activity were found to be significantly higher in postpartum samples than in specimens obtained from the nonpregnant or early pregnant cervix. After sulprostone treatment enzymatic activities were only marginally elevated. Analysis of extractable peptides showed that sub partu collagen was degraded in preference to noncollagenous proteins into very small fragments, whereas in the process of prostaglandin-induced cervical ripening collagen degradation appears to be of minor importance.

Vaginosonographic detection of endometrial cancer in postmenopausal women

In a prospective study 155 postmenopausal women not on hormone treatment underwent a vaginal ultrasound investigation. All women were routine patients of the regular ambulance. In addition to uterus biometry, the endometrial thickness was also measured. An endometrium of ≥4 mm thickness was clarified histologically by means of a curettage. In total we found 7 endometrial cancers and 1 cervical cancer. Vaginal sonography proved to be a very sensitive (81%) and specific (89%) method for the detection of endometrial neoplasia.

Objective demonstration of cervical softening with a prostaglandin F2α gel during first trimester abortion

In a prospective study the cervix softening and dilating effects of intracervically applied prostaglandin F2α gel were investigated in 100 patients during induced abortion in the 7–12th week of pregnancy. A specially designed tonometer was used to measure the resistance of the cervical canal before as well as 6–8 h, 4 days and 5–6 weeks after gel application. The cervix of 99 patients proved to be freely passable without use of undue force for at least Hegar 8 after treatment. Measurements in 96 patients 5–6 weeks after the operation showed good general agreement with those values obtained before gel application. No spontaneous or operation‐induced lesions of the cervix occurred. Intracervical prostaglandin gel application proved itself to be a safe, practicable and gentle method for avoiding dilation‐induced complications during first trimester abortions.

Changes in collagen content of the first trimester cervix uteri after treatment with prostaglandin F2α gel

SummaryEight hours after intracervical instillation of prostaglandin F2α gel we found a reduction in the collagen content of the cervix such as occurs at term. This suggests that prostaglandin brings about ripening and dilatation of the cervix in a physiological manner.

Medical prevention and treatment of postpartum hemorrhage: a comparison of different guidelines

BackgroundPostpartum hemorrhage (PPH) remains a common cause of maternal mortality worldwide, mainly caused by uterine atony. Medical intervention plays an important part in prevention and therapies of PPH. Prophylactic interventions include the use of uterotonic drugs. We elaborated the consistency of national and international guidelines on those medical approaches.Materials and methodsMedical approaches in PPH were extracted from recent publications. Furthermore, the current guidelines of the World Health Organization, the FIGO and of the American, British, Canadian and German Societies of Obstetricians and Gynecologists on PPH were analyzed.ResultsOxytocin is considered as therapy of first choice. However, the examined guidelines fail to give unequivocal recommendations on further uterotonics in PPH, which may partially be attributed to differing publication dates of the guidelines.ConclusionInternational guidelines on PPH are characterized by differing recommendations. However, recent publications suggest that adhering to local guidelines significantly reduces the prevalence of severe PPH.