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To evaluate clinical-pathological aspects of mitotically active leiomyomas.Twenty patients with smooth muscle tumors of the uterus, with 5-9 mitotic figures per 10 high power fields and without atypia or necrosis were studied. The clinical and pathological characteristics of these tumors were reviewed and analyzed.Patients' ages ranged from 33 to 63 years (mean 42.5 years). The size of the tumors ranged from 1.5 to 9.5 cm (mean 5.4 cm). On gross examination all tumors appeared as typical leiomyomas. Treatment included hysterectomy in 16 patients and myomectomy in four. Follow-up periods ranged from 1.5 to 11 years (mean 6.8 years). None of the patients developed a recurrent tumor.The benign clinical behavior of such tumors supports their current designation as mitotically active leiomyomas, thus deleting the previous misnomer 'smooth muscle tumors of uncertain malignant potential'. Myomectomy is an appropriate treatment, particularly in young patients interested in reproduction.

OBJECTIVE: The aim of this study was to assess the association of diagnosis and treatment delay with established prognostic factors and survival. STUDY DESIGN: The study group comprised 181 consecutive patients with endometrial carcinoma diagnosed between 1970 and 1986, whose records contained details with regard to diagnosis delay; 174 of them also contained details with regard to treatment delay. RESULTS: The significant prognostic factors that we found, namely, age, clinical stage, grade, depth of myometrial invasion, and histologic type, are in line with those of other studies. However, no significant correlation was found between the duration of delay and these prognostic factors or with survival. CONCLUSION: We conclude that delay of diagnosis (

PURPOSE: To study the role of BRCA mutations in ovarian cancer survival. PATIENTS AND METHODS: Blood samples and specimens of ovarian tumors (whenever blood samples were not available) at the time of the primary surgery were obtained in the course of a nationwide case-control study of women with ovarian cancer in Israel. The three common BRCA mutations in Israel (185delAG, 5382insC, and 6174delT) were analyzed with a multiplex polymerase chain reaction to amplify the exons containing the three mutations using fluor-labeled primers in a single reaction. Because each mutation is a small insertion or deletion, they can be detected as length polymorphisms. Patients were followed for up to 5 years (range, 20 to 64 months). Statistical analysis was performed using the Kaplan-Meier method and the log-rank test. Stepwise Cox regression analysis was used for determination of independent prognostic factors. RESULTS: This report is based on 896 blood or tumor specimens analyzed for the presence of the BRCA mutations. Of these, 234 women (26.1%) were found to be positive. A significant difference in survival pattern was found between BRCA1/BRCA2 carriers and noncarriers among the women with invasive ovarian cancer (median survival, 53.4 months v 37.8 months; 3-year survival, 65.8% v 51.9%, respectively). These differences were independent of age at diagnosis or stage of the disease. CONCLUSION: Our data indicate that the survival of patients with ovarian cancer is affected by BRCA germline mutation, at least in the early years after diagnosis.

To analyze the possible correlation between expression of the alphav and beta1 integrin chains and survival in advanced-stage ovarian carcinomas, studying two patient groups with extremely different disease outcome.Sections from 56 primary ovarian carcinomas and metastatic lesions from 34 patients diagnosed with advanced-stage ovarian carcinoma (Fédération Internationale des Gynaecologistes et Obstetristes stages III-IV), divided into long-term (16) and short-term (18) survivors, were evaluated for expression of alphav and beta1 integrin chains using mRNA in situ hybridization. Protein expression was additionally studied in 52 specimens using immunohistochemistry.The mean values for disease-free survival and overall survival were 115 and 132 months for long-term survivors, as compared with 4 and 23 months for short-term survivors, respectively. Expression of alphav integrin mRNA was observed in carcinoma (18 of 56; 32%) and stromal (17 of 56; 30%) cells. beta1 integrin mRNA was similarly detected in carcinoma (25 of 56; 47%) and stromal (19 of 56; 34%) cells. No significant differences were observed when primary and metastatic lesions were compared (P0.05). Alphav integrin mRNA was present more often in carcinoma cells in tumors of short-term survivors (P = 0.017 for carcinoma cells). In univariate survival analysis for all cases, alphav integrin mRNA expression in tumor cells correlated with poor survival (P = 0.012). This finding retained its predictive power in a multivariate survival analysis, in which all of the molecules studied previously in this patient cohort were included (P = 0.031). Immunohistochemistry confirmed the differences in alphav integrin expression in tumor cells of short-term as compared with long-term survivors, whereas beta1 integrin protein expression was comparable in the two groups.To our best knowledge, this is the first evidence associating integrin expression with poor survival in ovarian carcinoma. Alphav integrin is, thus, a novel prognostic marker in advanced-stage ovarian carcinoma.

Angiogenic factors play a role in tumor growth and spread. The object of this study was to analyze the correlation between mRNA expression of angiogenesis-related genes and disease outcome in advanced-stage ovarian carcinomas. Sections from 66 primary ovarian carcinomas and metastatic lesions from 41 patients diagnosed with advanced stage ovarian carcinoma (FIGO stages III-IV) were evaluated for expression of basic fibroblast factor (bFGF), interleukin-8 (IL-8), and vascular endothelial growth factor (VEGF) using mRNA In Situ Hybridization (ISH). Patients were divided in two groups based on disease outcome. Long-term survivors (17 patients) and short-term survivors (24 patients) were defined using a double cut-off of 36 months for disease-free survival (DFS) and 60 months for overall survival (OS). Mean follow-up period was 70 months. The mean values for DFS and OS were 116 and 133 months for long-term survivors, as compared to 3 and 21 months for short-term survivors, respectively. Expression of bFGF mRNA, most often intense, was detected in tumor and stromal cells in the majority of cases. Weak expression of IL-8 mRNA was detected in both cell compartments, while VEGF mRNA expression was limited to few cases. Primary tumors displayed higher bFGF and IL-8 mRNA expression. However, these differences did not reach statistical significance (P0.05). bFGF, IL-8 and VEGF mRNA expression in both tumor and stromal cells was comparable in tumors of long-term and short-term survivors, and showed no correlation with disease outcome in survival analysis (P0.05). bFGF is the major angiogenic factor expressed in ovarian carcinoma at the mRNA level. mRNA expression of VEGF, bFGF, and IL-8 does not appear to be a predictor of disease outcome in advanced-stage ovarian carcinoma.

Ets-1 proto-oncogene is a transcription factor involved in several cellular functions, including the activation of several proteases participating in tumor invasion and metastasis. The objective of this study was to analyze the possible correlation between Ets-1 mRNA expression and survival in advanced-stage ovarian carcinomas, studying two patient groups with extremely different disease outcome. Sections from 66 primary ovarian carcinomas and metastatic lesions from 41 patients diagnosed with advanced-stage ovarian carcinoma (International Federation of Gynecologists and Obstetricians stages III and IV) were evaluated for expression of Ets-1 using mRNA in situ hybridization. Patients were divided into long-term (n = 17) and short-term (n = 24) survivors. The mean values for disease-free survival and overall survival were 116 and 133 months for long-term survivors, as compared to 3 and 21 months for short-term survivors, respectively. Expression of Ets-1 mRNA was detected in carcinoma cells and stromal cells in 28 of 66 (42%) and 22 of 66 (33%) lesions, respectively. Ets-1 expression showed an association with mRNA expression of vascular endothelial growth factor (P = 0.001 for carcinoma cells; P = 0.004 for stromal cells), basic fibroblast growth factor (P = 0.049 for carcinoma cells), and membrane type-1 matrix metalloproteinase (P = 0.045), which were previously studied in this patient cohort. Ets-1 mRNA was detected more often in both carcinoma and stromal cells in tumors of short-term survivors (P = 0.038 for carcinoma cells). In univariate survival analysis for all cases, Ets-1 expression in both tumor (P = 0.018) and stroma (P = 0.026) correlated with poor survival. These findings were reproduced in an analysis of primary tumors alone (P = 0.039 for tumor cells; P0.001 for stromal cells). Ets-1 mRNA expression in stromal cells retained its predictive power in a multivariate survival analysis in which all molecules studied previously in this patient cohort were included (P = 0.007). To our knowledge, this is the first evidence associating Ets-1 mRNA expression and poor survival in human epithelial malignancy. Ets-1 is thus a novel prognostic marker in advanced-stage ovarian carcinoma. The association between Ets-1 mRNA expression and the expression of membrane type-1 matrix metalloproteinase and angiogenic genes, first documented here in a study of patient material, points to the central role of this transcription factor in tumor progression in ovarian carcinoma.

The object of this study was to analyze the potential association between the expression of MMP-2, MMP-9, MT1-MMP and TIMP-2, and disease outcome in advanced-stage ovarian carcinomas. Sections from 70 paraffin-embedded blocks (36 primary ovarian carcinomas and 34 metastatic lesions) from 45 patients diagnosed with advanced stage ovarian carcinomas (FIGO stages III-IV) were studied using mRNA in situ hybridization (ISH) technique. Patients were divided retrospectively in two groups based on disease outcome. Long-term survivors (21 patients) and short-term survivors (24 patients) were defined using a double cut-off of 36 months for disease-free survival (DFS) and 60 months for overall survival (OS). Mean follow-up period for patients that were diagnosed with advanced-stage carcinoma was 70 months. The mean values for DFS and OS were 109 and 125 months for long-term survivors, as compared to 3 and 21 months for short-term survivors, respectively. Intense mRNA signals were detected more frequently in tumor cells of short-term survivors with use of all four probes. Comparable findings were observed in peritumoral stromal cells with ISH for MMP-2, MMP-9 and TIMP-2 mRNA. Notably, primary tumors with intense mRNA signal for TIMP-2 (No = 14) were uniformly associated with a fatal outcome. In univariate analysis of primary tumors, mRNA levels of TIMP-2 in stromal cells (P = 0.0002), as well as for MMP-9 (P = 0.012) and TIMP-2 (P = 0.02) in tumor cells, correlated with poor outcome. In univariate analysis of metastatic lesions, mRNA levels of TIMP-2 in stromal cells (P = 0.031), as well as for MMP-2 (P = 0.027) and MT1-MMP (P = 0.008) in tumor cells, correlated with poor outcome. Interestingly, the presence of MT1-MMP in stromal cells correlated with longer survival (P = 0.025). In a multivariate analysis of ISH results for primary tumors, TIMP-2 levels in stromal cells (P = 0.006) and MMP-9 levels in tumor cells (P = 0.011) retained their predictive value. We conclude that MMP-2, MMP-9, MT1-MMP and TIMP-2 are valid markers of poor survival in advanced-stage ovarian carcinoma.

There is inherited predisposition to breast and ovarian cancer in 5-10% of all women with these diseases. Germline mutations in BRCA1 and BRCA2 presumably account for most of the genetically susceptible individuals. We summarize 2 years of experience in counseling and testing for inherited predisposition to these cancers. 597 women (from 320 families) have been evaluated since August 1995. 242 were evaluated for inherited predisposition to breast and ovarian cancer. One-third had clear-cut evidence of familial background. 74 families were of Ashkenazi origin; the age range of breast cancer was 30-35, of ovarian cancer 40-45. In 80% of families other cancers were also noted in first degree family members, including lung, colon, and prostate cancer and leukemia. Genetic testing revealed that 45% of affected and 25% of unaffected women were carriers of a mutation in BRCA1 or BRCA2: 67/90 185delAG (BRCA1), 12/90 6174delT (BRCA2), and 4/90 of 5382insC (BRCA1). In addition, a novel mutation in exon 11 of BRCA1 was detected, carried by 7/90 women. The experience gained in oncogenetic counseling and genetic testing for inherited cancer predisposition will eventually enable determining an optimal, rational therapeutic regimen in carriers of mutations.

A single germ line mutation in BRCA1 , (185delAG) is detected in a substantial portion of Jewish Israeli patients with ovarian cancer. Whether disease phenotypes differ in BRCA1 mutation carriers and sporadic cases is presently a subject for debate. To gain insight into this issue, we analysed tumours from 65 Jewish women with ovarian cancer, 29 (45%) were 185delAG BRCA1 mutation carriers, and 36 (55%) were non-carriers of any of the predominant Jewish mutations in BRCA1 or BRCA2 (sporadic). In 19/29 mutation carriers (66%) diagnosis was made prior to age 60 years, compared with 14/36 (39%) of the non-carriers ( P =0.03; Yates corrected P =0.06). Low malignant potential (‘borderline’) tumours were detected less frequently among carriers (2/29; 7%) than non-carriers (9/36; 25%) ( P =0.03; one tail P =0.05). Immunohistochemical analysis in invasive carcinoma ( n =54) showed that 17/27 carriers (63%) and 18/27 non-carriers (67%) had positive nuclear staining with a p53 antibody. In 4/27 carriers (15%) and 3/25 non-carriers (12%), 25% or more of the tumour cells stained positive for Ki-67, an insignificant difference. Results were not altered by including borderline tumours ( n =11) in these analyses. We conclude that the rate of TP53 inactivation and proliferative index in ovarian cancer, are similar for 185delAG BRCA1 mutation carriers and sporadic cases.

CD44 is an integral membrane glycoprotein, functioning as the receptor for hyaluronic acid. CD44 is expressed on epithelial, mesenchymal, lymphoid, and glial cells. CD44 distribution, pattern of staining, and isoform types are altered in neoplastic conditions, including cervical dysplasia and carcinoma. We have studied CD44 expression by immunohistochemistry in 49 patients with cervical intraepithelial neoplasia (CIN) I, II, III invasive squamous cell carcinoma of the uterine cervix and controls. Only membranous staining was considered positive. Diffuse membranous staining was observed in all controls and CIN I cases, but only in 7/10, 3/10, and 4/9 cases of CIN II, CIN III and squamous cell carcinoma, respectively. The remaining cases showed either complete lack of staining, only focal membranous staining or only diffuse inconsistent (weak/cytoplasmic/fragmented) staining. Three invasive carcinomas showed both areas of membranous staining and areas of inconsistent staining in the same section. No correlation was observed between tumor grade and CD44 pattern of staining. Human papillomavirus (HPV) was found in 24/29 high-grade intraepithelial lesions and carcinomas. HPV expression did not correlate with CD44 staining. In conclusion, CD44 expression was found to be reduced in more than 50% of high-grade intraepithelial neoplastic lesions and invasive carcinomas. This might be associated with the loss of cellular adhesion characteristics of pre-invasive and invasive lesions. HPV presence did not seem to influence CD44 expression.

To outline the sonographic and color Doppler flow imaging characteristics of ovarian tumors of low-malignant potential (OCLMP).Fourteen women with ovarian tumors of low-malignant potential were compared with 26 women with ovarian cystadenomas and 23 with ovarian carcinomas.Sonographically, more complex structures and echogenic lesions were found in the OCLMP and malignant tumors than in the cystadenomas, and the difference was statistically significant. Color blood flow imaging revealed a similar resistant index (RI) in the OCLMP (0.487 +/- 0.07) and cystadenomas (0.489 +/- 0.09) when compared with statistically significant lower RI in the ovarian carcinomas (0.391 +/- 0.05) (P0.001).Among young women, the combination of a complex ovarian mass with turbid fluid and echogenic lesions whose color Doppler flow imaging registers in the low range (RI0.5) should raise the suspicion of an ovarian tumor of low-malignant potential.

To determine the role of BRCA1 185delAG mutation in ovarian carcinogenesis.Genetic testing of a subset of cases from an ongoing study of ovarian cancer and of controls.A community-based case-control incidence study.Seventy-nine patients with ovarian cancer, 62 hospitalized women without cancer (controls), and 120 healthy women participating in a fragile X screening program (also controls), examined for the presence of germline BRCA1 185delAG mutation.Polymerase chain reaction-amplified BRCA1 exon 2 fragments generated from patients' and controls' blood samples, analyzed by heteroduplex gel shift assay and direct sequence analyses.The 185delAG mutation was detected in 38.9% (7/18) of ovarian cancer patients with familial history, and 13.1% (8/61) of family history-negative ovarian cancer cases. Only 1 carrier was detected among the 120 healthy controls, and none in the hospital controls. A significant difference in mutation carrier rates between family history-negative cases and control groups of 120 and 62 subjects was identified (Fisher exact test, P=.001 and P=.003, respectively). The median age (+/-SE) at disease diagnosis was lower among both familial and family history-negative mutation carriers, as compared with mutation-negative, family history-negative cases--50 (+/-1.4) vs 60.5 (+/-3.5) years old, respectively (hazard ratio, 1.68; 95% confidence interval, 0.94-3.01).Our data are preliminary but suggest that BRCA1 185delAG germline mutation is frequent in Israeli ovarian cancer patients, irrespective of family history, and may confer an early-onset phenotype of ovarian cancer

We assessed the efficacy of short term intraperitoneal treatment with cisplatin (200 mg/m2) and etoposide (300 mg/m2) in 21 ovarian carcinoma patients who were in complete clinical remission after completion of postoperative cisplatin based chemotherapy. Second-look laparotomy was done in 17 patients prior to intraperitoneal chemotherapy and in 10, minimal residual disease was found. The mean follow-up was 24 (range 9-54) months. The projected overall survival 54 months after diagnosis was 60% and the median PFI 26 months. The median survival and PFI of patients with minimal residual disease at second-look laparotomy was only 27 and 18 months respectively. In all patients with relapse the recurrence was intraperitoneal. The combination intraperitoneal chemotherapy schedule used does not seem to be more effective for ovarian carcinoma patients who are clinically in complete remission than the intraperitoneal treatment with cisplatin alone reported in other series.

In a previously published study we compared the outcome probability within 3 years after diagnosis in two groups of advanced ovarian carcinoma patients in complete clinical remission with minimal or no residual disease at second look laparotomy, performed after completion of cisplatin based combination chemotherapy. One group (n = 18) received after reexploration, abdominopelvic irradiation (RT group), the other diagnosed during a later period (n = 19), received after reexploration three courses of introperitoneal cisplatin chemotherapy with systemic thiosulfate protection (IP) group). In the present study the outcome of the same patients is compared after they have all been followed for at least 5 years or till death. A clear trend towards a more favorable, through statistically not significant, 5 year survival was observed (68%), in the IP group, vs 39% in the RT group (p = 0.07). In patients with a negative second-look laparotomy, the respective 5 year survival rates were 92% and 60% (p = 0.08). While the duration of the progression-free interval was similar in both treatment groups the survival after diagnosis of recurrence was significantly better in the IP group (41% vs 0%, p = 0.03).

The clinical presentation, surgico-pathologic findings and the outcome are described of seven patients with carcinoma of the endometrium, which developed remote after cervical amputation as a treatment for cervical elongation. In six patients, cervical stenosis prevented early uterine bleeding. Four patients when diagnosed, were in advanced surgical stages of the disease (Stages II and III) and all died thereafter. Three patients with surgical Stage I, had no evidence of disease 33, 96, 151 months, after diagnosis and treatment. The role of cervical stenosis in delayed diagnosis and treatment, and therefore poor prognosis is discussed. When cervical stenosis is anticipated, periodic ultrasonographic evaluation of the endometrium is justified, in order to prevent a delay in making a diagnosis of endometrial carcinoma.

Endothelins, potent stimulators of smooth muscle tissue activity, were recently shown to also function as mitogens for numerous cell types. The authors investigated the properties of endothelin-1 (ET-1) receptors in human endometrial tissue compared with human endometrial carcinoma tissue.Tissue samples from 13 patients with endometrial carcinoma and from 12 women undergoing hysterectomy due to uterus myomatous were obtained immediately after surgical removal. Binding properties of the endothelin receptors were studied using 125I-labeled ET-1.A significant difference was demonstrated between binding properties of ET-1 receptors of these two groups. The mean maximal density (Bmax) value of the normal endometrial samples was 2029 +/- 341 fmol/mg protein, whereas that of the neoplastic samples was 356 +/- 121 fmol/mg protein. No differences were found, however, between the mean dissociation constant (Kd) values of these groups.These results might be compatible with the increased blood flow that characterizes malignant endometrial tissue. However, they do not indicate an important mitogenic role for ET-1 in the development of endometrial cancer.

To assess the feasibility of using cytologic examination of ovarian cyst fluid for distinguishing between benign and malignant tumors.Cyst fluid was aspirated at surgery in 83 women with benign and 35 women with malignant (25 invasive and ten borderline) ovarian tumors and submitted for routine cytologic examination.The specificity of the cytologic examination was 100%, but the sensitivity and negative predictive value were only 26 and 76%, respectively.The low sensitivity and negative predictive value of cytologic cyst fluid examination preclude its use for the distinction between benign and malignant ovarian tumors.

To assess the feasibility of using cyst fluid CA 125 levels to distinguish between benign and malignant ovarian cystic neoplasms.CA 125 levels were measured in ovarian cyst fluid and in serum obtained at surgery in 44 women with ovarian cystic tumors of epithelial origin (25 benign, 12 malignant, and seven borderline).The median cyst fluid CA 125 level in malignant neoplasms (671 U/mL) was higher than in benign tumors (175 U/mL), and 86% of the malignant tumors contained levels higher than 100 U/mL in the cyst fluid, compared with only 62% of the benign tumors. However, these differences were not statistically significant.Cyst fluid levels of CA 125 cannot be used to distinguish between benign and malignant ovarian cysts of epithelial origin.

Labor characteristics in 89 women undergoing a second vaginal delivery 10-18 years after the first were compared retrospectively with those of 136 women with an interval of 1-4 years between their first and second vaginal deliveries and with those of 128 nulliparous women. The pelvic findings on admission, average length of stages 1 and 2 of labor, average cervical dilation per hour and rates of surgical intervention in relation to arrest disorders were similar in the two multiparous groups and significantly different from these parameters in the nulliparous group. Women with long intervals between their first and second vaginal deliveries should be managed in the same way as are other multiparas and not like nulliparas with respect to such issues as indications for oxytocin treatment, surgical intervention and use of conduction anesthesia.

Effective second line chemotherapy schedules for recurrent ovarian carcinoma are not available. The combination of cisplatin and VP-16 given as a single dose in such patients gave inconsistent results. Since VP-16 is a dose-schedule dependent drug it was given in this pilot study as a continuous 72 hour infusion at a dose of 100 mg/m2/day. No objective response was observed among 7 patients with refractory or recurrent ovarian carcinoma who received a median of 3 treatment courses.

The CT findings in 6 women with puerperal sepsis after Cesarean section were reviewed. In four patients a right-sided mass was palpated. CT scan confirmed the diagnosis of Tubo-ovarian abscess in two of the patients, puerperal ovarian vein thrombosis (POVT) in the third and an enlarged adnexa with no signs of abscess formation in the fourth patient. The last two patients had normal adnexae but a large amount of gas in the uterus. All patients recovered after appropriate treatment. In patients with severe puerperal sepsis who do not respond to antibiotic therapy, CT scanning of the abdomen and pelvis is useful. This study can demonstrate whether there is an abscess which requires surgical intervention or POVT which needs additional anticoagulant treatment.

Among 114 women with early spontaneous abortions, low beta-human chorionic gonadotropin levels and no ultrasonographically demonstrable residual tissue in the uterine cavity, 68 underwent uterine curettage, and 46 were managed conservatively. No complications, such as bleeding or infection, were observed in either group, and the probability of conception, outcome of subsequent pregnancies and rate of subsequent abortions were similar. Curettage offers no advantage over conservative management in selected patients with early abortions.

Of 207 women who underwent midtrimester induced abortion with intraamniotic prostaglandin F 2 alpha instillation, 30 (14.5%) had had one or more previous uterine operations. Multivariate analysis showed no correlation between a previous uterine operation and the hospitalization length, procedure complication rate or length of the injection-delivery interval (IDI). The IDI was similar in patients with and without a previous uterine operation. No case of uterine rupture occurred. Intraamniotic prostaglandin instillation for midtrimester abortion induction seems to be an effective procedure without severe complications in women with previous uterine operations.Of 207 women who underwent midtrimester induced abortion with intraamniotic prostaglandin (PG) F2alpha instillation, 30 (14.5%) had 1 or more previous uterine operations. Multivariate analysis showed no correlation between a previous uterine operation and the hospitalization length, procedure complication rate, or length of the injection-delivery interval (IDI). The IDI was similar in both patients with and without a previous uterine operation. No case of uterine rupture occurred. Intraamniotic PG instillation for midtrimester abortion induction seems to be an effective procedure without severe complications in women with previous uterine operations.

Following a rollover test performed in 306 nulliparous women in the 28th gestational week, Doppler flow velocity studies were conducted in all 34 women with positive rollover findings and in 67 women selected at random from those with negative findings. The mean systolic diastolic ratios in both the uterine and the umbilical arteries were significantly higher in women with positive rollover findings than in the control group. A review of the patients' medical records after delivery, indicated that this combined two-stage screening approach--a rollover test followed by a Doppler flow study--improved the predictive value and the sensitivity of the screening procedure from 35% and 39% respectively for the rollover test alone, to 56% and 50% with no decline in specificity. The sensitivity of the Doppler flow test as a single one among the 101 flow-studied women was higher--61%. However, broader studies are needed in order to establish its superiority as a single test for early prediction of pregnancy-induced hypertension.

A consistently higher rate of abnormal cervical cytology, colposcopic and histologic findings in 89 DES exposed Israeli Jewish women was found as compared to 318 women in a control group. This trend however reached statistical significance for abnormal colposcopic and histologic findings only in the 25-34 age group. The higher rate of abnormal findings can be attributed to DES exposure and not to an excess of other risk factors in the study group. Routine cytologic and colposcopic examination is recommended for DES exposed Israeli Jewish women who are otherwise at low risk for development of cervical neoplasia.

Among two hundred and twenty-one patients admitted with the diagnosis of pelvic inflammatory disease (PID), 6 had an underlying malignancy. The rate of underlying malignancy was 1.4% in premenopausal patients and 42.8% in postmenopausal patients. This difference was statistically significant, p less than 0.001. In postmenopausal patients presenting with a pelvic inflammatory process pelvic malignancy should be highly suspected and thorough examination made.

Amniotic fluid volume was measured in two ways in 23 subjects admitted for interruption of pregnancy at gestational ages 16-24 weeks. The amniotic fluid volume calculated from sonographic measurements was plotted against the "true" amniotic fluid volume obtained by a dye dilution technique. Linear regression analysis showed a good correlation between the two methods (r = 0.815; P less than .001) and yielded a factor that may be used on a general basis to derive the true amniotic fluid volume from the value obtained by sonography. This approach thus offers a standardized procedure for amniotic fluid volume estimation in the second trimester based on the technical simplicity of ultrasonography with the relative accuracy of the dye dilution technique.

Three patients with primary breast carcinoma and metastases to the endometrium presented with postmenopausal bleeding. All patients had locally advanced breast cancer at the time of diagnosis, and all developed other distant metastases concomitantly or shortly after the diagnosis of endometrial involvement. The treatment of breast carcinoma metastatic to the endometrium is palliative. Distinguishing metastatic carcinoma from primary endometrial carcinoma is of great practical clinical significance, since in the latter surgical intervention is indicated.

(1990). Systemic adverse reaction to an oxytocin preparation. Journal of Obstetrics and Gynaecology: Vol. 10, No. 3, pp. 224-225.

The effects of L-T4 and betamethasone treatment of newborn mice oft the develoment of the cholinergic muscarinic receptor in certain? brain regions was studied using the potent labeled muscarinic antagonist [3H]4-iV-methyl-piperidyl benzilate. Treatment with both L-T4 and betamethasone caused an accelerated accumulation of muscarinic receptors in the cortex 16 days post partum, with a subsequent reduction in level at 30 days. In the cerebellum and caudate putamen, only betamethasone caused a similar early accumulation of muscarinic receptors, while the later effect, namely a reduction in the level at 30 days, was seen with both hormones in these two regions as well as in the hippocampus. The results can explain some behavioral effects observed in other studies after treatment with these hormones.

High levels of prenylated protein methyltransferase are expressed in the developing rat cerebellum and are responsible for methylation of endogenous G-proteins and 50–52 kDa synaptosomal proteins. Enzyme activity in cerebellar synaptosomes of 3 week postnatal rats is 2-fold higher than that found in adult rat cerebellum. A 10-fold rise in activity occurs at the end of the second and during the third postnatal weeks, followed by a subsequent decline. Expression of the enzymes' substrates follows the same pattern. The high methyltransferase activity in 3-week-old cerebellum coincides with the period of granule cell migration and synaptogenesis, suggesting a regulatory role for the enzyme and its substrates in cerebellar ontogenesis.

The introduction of laparoscopy as a routine diagnostic tool for pelvic disorders has prompted its use in the management of uterine perforation as well. A retrospective review of 52 patients with uterine perforation secondary to curettage is presented. In 23 (44.2%) the curettage was discontinued, and the postperforation course was uneventful. Eight patients (15.4%) underwent immediate exploratory laparotomy without laparoscopy; in three of them no internal organ injury or bleeding was found. Eighteen patients (34.6%) underwent postperforation laparoscopy; seven of these women underwent subsequent laparotomy. The indications and objectives of postperforation laparoscopy are outlined. Its judicious use allows proper selection of patients for exploratory laparotomy.

Prenatal real-time ultrasonographic diagnosis of exophthalmus is presented. Diagnosis was made at the 35th week of gestation in a fetus of a patient affected with Crouzon syndrome (craniofacial dysotosis). Recognition of exophthalmus as a part of Crouzon syndrome and the easy visualization of the eye balls and palpebrae in the third trimester made the diagnosis possible.

A 29-year old, gravida 2, para 2, presented with colicky lower abdominal pain and vaginal bleeding. A Saf-T-Coil had been inserted 8 months previously. Due to menometrorrhagia, she was treated wtih methylergometrine maleate (Methergin), 0.125 mg thrice daily for from 2 weeks until 1 week prior to admission. Examination revealed perforation of the posterior cervical lip by the vertical limb of the IUD. The purpose of the presentation is to alert physicians to the possible etiologic role of Methergin in this complication. (author's)

The initial postoperative treatment of 31 patients with stage I-II ovarian cancer of epithelial origin, consisted of abdominopelvic radiotherapy. The 5-year survival was significantly better in stage I as compared to stage II (81.1% vs 36.3%). There was a consistent trend in both stages for better outcome in grades 1-2. This trend, however, reached statistical significance only for PFI. Most of the patients with recurrent disease had grade 3 tumors. While satisfactory treatment results may be achieved with postoperative radiotherapy for stage I-II tumors which are well or moderately differentiated, it is not recommended for undifferentiated tumors.

Reassessment of the pathological slides of 31 Israeli patients confirmed the initial diagnosis of uterine sarcoma in 28 cases. The review diagnosis of the histological subcategory was not always identical with the original one. The most common tumor (32.1%) was mixed heterologous sarcoma. Abnormal bleeding was the most common symptom and a presumed myomatous uterus the most common clinical finding. Although almost half the patients were diagnosed in Stage I, the overall survival was 26%. Survival was influenced by both the stage at diagnosis and the histological category.

The possible interaction between the muscarinic receptors and the antiestrogenic drug clomiphene citrate was investigated in competition experiments using the highly specific tritiated antagonist N-methyl-4-piperidyl benzilate (4-NMPB) in various regions of rat brain. It was found that clomiphene can displace muscarinic antagonists from their receptor-ligand complexes. Binding analyses as well as determinations of the kinetics of dissociation of [3H]4-NMPB-receptor complexes indicate the binding of more than one molecule of clomiphene in a positively cooperative pattern. These findings suggest that the nonsteroidal antiestrogenic drugs, e.g., clomiphene, might exert their effects not only through the specific estrogen receptor but also in conjunction with the muscarinic system.

Over a period of eight years, 13,344 consecutive patients underwent curettage in our hospital for various indications. Uterine perforation occurred in 22 (0.16%) of them. An additional seven patients were admitted with existing uterine perforation. The most common site of perforation was the uterine fundus and the instrument most often involved was a sharp curette. The perforation rates in curettage performed for postpartum hemorrhage and intrauterine adhesions were relatively high (5.1 and 1.8%, respectively); the rates in those for elective abortion and postmenopausal bleeding were intermediate (0.4 and 0.2%, respectively); and in those performed for other indications, the rate was very low (less than or equal to 0.06%). After uterine perforation occurred 15 patients (51.7%) were managed by observation only and the course was uneventful. In 10 patients (34.5%), exploratory laparotomy was performed; in three of them, no active bleeding organ injury was found. Judicious use of laparoscopy after uterine perforation allows proper selection of patients for further surgery.