Amiram Bar-Am

Vascular endothelial growth factor is increased in patients with preeclampsia.

PROBLEM: This study was conducted to determine whether altered levels of vascular endothelial growth factor (VEGF) may play a role in the pathogenesis of preeclampsia.

Mid‐trimester severe intrauterine growth restriction is associated with a high prevalence of thrombophilia

Objective To investigate the association between severe mid‐trimester IUGR, whose causes are unknown in most cases, and maternal thrombophilias.

Plasma interleukin-12 is elevated in patients with preeclampsia.

PROBLEM: Abnormal immune activation has been suggested as a contributor to the development of preeclampsia. We hypothesized that intact interleukin (IL)‐12 directly, or through its main mediator, interferon (IFN)‐γ, contributes to the altered immune response observed in preeclampsia.

Levels of vascular endothelial growth factor are elevated in patients with ectopic pregnancy: is this a novel marker?

OBJECTIVE To determine serum levels of vascular endothelial growth factor (VEGF) and evaluate their capacity to serve as a marker for the diagnosis of ectopic pregnancy (EP). DESIGN Prospective, case-controlled study. SETTING A tertiary care center. PATIENT(S) Twenty women with EP, 10 women with normal intrauterine pregnancy, and 10 women with abnormal intrauterine pregnancy, all at comparable stages of gestation. INTERVENTION(S) Serum samples were obtained from all women. MAIN OUTCOME MEASURE(S) All samples were analyzed for VEGF, progesterone, and beta-hCG by specific methods. RESULT(S) Women with EP had higher serum levels of VEGF than women with normal intrauterine pregnancy and women with abnormal intrauterine pregnancy (median levels, 226.8 pg/mL, 24.4 pg/mL, and 59.4 pg/mL, respectively). With a cutoff level of 200 pg/mL, serum VEGF could distinguish intrauterine from extrauterine pregnancy with a sensitivity of 60%, specificity of 90%, and positive predictive value of 86%. CONCLUSION(S) The increased serum VEGF levels in women with EP may facilitate this challenging diagnosis and reduce maternal morbidity and mortality.

The Classic Approach to Diagnosis of Vulvovaginitis: A Critical Analysis

OBJECTIVE To correlate the symptoms, signs and clinical diagnosis in women with vaginal discharge, based on the combined weight of the character of the vaginal discharge and bedside tests, with the laboratory diagnosis. METHODS Women presenting consecutively to the womens health center with vaginal discharge were interviewed and examined for assessment of the quantity and color of the discharge. One drop of the material was then examined for pH and the whiff test was done; a wet mount in saline and in 10% KOH was examined microscopically. The clinical diagnosis was based on the results of these assessments. Gram stain and cultures of the discharge were sent to the microbiology laboratory. RESULTS One hundred and fifty-three women with vaginal discharge with a clinical diagnosis of vulvovaginitis participated in the study. Fifty-five (35.9%) had normal flora and the other 98 (64.1%) had true infectious vulvovaginitis (kappa agreement = 18%). According to the laboratory, the principal infectious micro-organism causing the vulvovaginitis was Candida species. Candida infection was associated with pH levels of less than 4.5 (p < 0.0001, odds ratio = 4.74, 95% confidence interval: 2.35-9.5, positive predictive value 68.4%). The whiff test was positive in only a small percentage of bacterial vaginosis (BV) (p = not significant (NS)). Clue cells were documented in 53.3% of patients with a laboratory diagnosis of BV (p < 0.02, positive predictive value 26.7%). CONCLUSIONS The current approach to the diagnosis of vulvovaginitis should be further studied. The classical and time-consuming assessments were shown not to be reliable diagnostic measures.

The effects of tamoxifen treatment on the endometrium

OBJECTIVE To investigate the association between tamoxifen and endometrial cancer. BACKGROUND Tamoxifen is a nonsteroidal antiestrogenic drug that has been used successfully for 15 years in the treatment of all stages of breast carcinoma. In light of the positive results, several studies are now being conducted to test prolonged tamoxifen treatment as a prophylaxis against breast cancer in high-risk women. Although tamoxifen was thought to have only a few side effects, reports indicate that it is associated with an increased incidence of proliferative and neoplastic changes in the endometrium. As the current trend is to administer tamoxifen for prolonged periods and for more indications, the detrimental effects on the endometrium have vast implications. METHODS Review of the current literature. RESULTS Tamoxifen treatment is associated with an increased incidence of proliferative and neoplastic changes in the endometrium, with a 1.3 to 7.5 relative risk of developing endometrial carcinoma. CONCLUSIONS The results of tamoxifen treatment in breast carcinoma override the risk of developing endometrial carcinoma. Any vaginal bleeding in women treated with tamoxifen should be investigated carefully and promptly. In the future it may be necessary to advise these women to undergo routine uterine cavity examination.

Follow-up by combined cytology and human papillomavirus testing for patients post-cone biopsy: results of a long-term follow-up

OBJECTIVE The goal of this study was to evaluate the clinical implications of integrating human papillomavirus (HPV) testing into a long-term follow-up and management protocol for women postconization for high-grade cervical intraepithelial neoplasia (CIN2-3). METHODS Sixty-seven women were followed-up by Pap smears and HPV type and load testing (mean follow-up, 63 months; range, 50-72). Patients with persistent abnormal cytology on two consecutive smears and those with positive HPV test results (whatever their cytologic findings) were referred for colposcopy-directed biopsy. Patients histologically diagnosed with CIN2-3 and those with high-load HPV (whatever their histologic findings) underwent repeat conization or hysterectomy for residual disease. RESULTS At follow-up, 29 (43.2%) women had positive cytology or positive HPV results and were referred for colposcopy. Eleven (37.9%) had high-grade cervical intraepithelial neoplasia or high-load HPV results and were further treated by reconization/hysterectomy. The respective positive predictive values of high-load HPV and low-grade squamous intraepithelial lesions were 100 and 60% for any CIN and 90 and 15% for CIN2-3. Only five of nine cases with a final diagnosis of CIN2-3 were originally identified by cytology: the other four were detected only by parallel evaluation by HPV testing. High-load HPV results with normal cytology or low-grade lesions harbored an 80% risk for CIN2-3. CONCLUSIONS Adding HPV load assessment to the follow-up protocol of women postconization due to CIN2-3 lesions could help detect high-grade residual disease among low-grade lesions and normal cytology cases while concomitantly and safely bestowing the advantage of lowering the rates of colposcopic referrals and surgical procedures.

Do soluble cell adhesion molecules play a role in endometriosis

PROBLEM: Endometriosis is a chronic inflammatory disease associated with diverse immunologic disturbances. Cell adhesion molecules are essential for the development of immune and inflammatory reactions. This study was conducted to investigate whether or not serum and peritoneal levels of soluble cell adhesion molecules are altered in women with endometriosis.
 METHOD OF STUDY: The study group comprised five women with moderate‐to‐severe endometriosis. Eight healthy women with a normal diagnostic laparoscopy served as controls. Serum and peritoneal fluid samples from both groups were analyzed for the soluble isoform of intercellular cell adhesion molecule‐1 (sICAM‐1), vascular cell adhesion molecule‐1 (sVCAM‐1), endothelial selectin (sES), and platelet selectin (sPS).
 RESULTS: Serum levels of sICAM‐1 were significantly increased in women with endometriosis (median levels: 410.4 ng/mL; range: 233.9 ng/mL–598.4 ng/mL vs. 235.7 ng/mL; range: 187.4 ng/mL–323.7 ng/mL; P=0.02). Although the levels of sVCAM‐1, sES, and sPS in both samples were higher in the study group, the differences did not reach significance.
 CONCLUSIONS: Our results suggest a role of ICAM‐1 in the pathophysiology of endometriosis. However, the role of other investigated cell adhesion molecules should be confirmed by further studies.

Efficacy of methotrexate treatment in extrauterine pregnancies defined by stable or increasing human chorionic gonadotropin concentrations

OBJECTIVE To evaluate the efficacy of methotrexate treatment in selected cases of extrauterine pregnancy (EUP) defined by stable or increasing hCG concentration. DESIGN Prospective cohort study. SETTING Gynecology department of the Lis Maternity Hospital. PATIENT(S) Fifty women with EUP diagnosed whenever an intrauterine gestational sac was not seen on transvaginal ultrasonography. INTERVENTION(S) Women received IM methotrexate at a dose of 50 mg/m(2) of body surface area. Failure of hCG levels to fall by >/=15% during any successive week resulted in repeated administration of methotrexate. Surgical intervention was performed for presumed tubal rupture. MAIN OUTCOME MEASURE(S) Serial hCG measurement was performed weekly until hCG concentration reached 15 mIU/mL. Success was defined as the achievement of hCG concentration of 25 mIU/mL without surgical intervention. RESULT(S) Forty-four women (88%) were successfully treated. The mean time from first methotrexate injection to success was 34 +/- 2.4 days. Women treated successfully and unsuccessfully differed significantly only with regard to serum hCG levels of 1,876 +/- 243 and 3,489 +/- 376 mIU/mL, respectively. When the initial hCG levels were lower or higher than 2,000 IU/L, the success rate was 97% and 74%, respectively (significant by Fishers exact test). CONCLUSION(S) When methotrexate treatment is administrated in a selected group of EUP defined by stable or increasing hCG, it may fail more frequently (26%) when initial hCG levels are >2,000 mIU/mL.

Effect of paracentesis of ascitic fluids on urinary output and blood indices in patients with severe ovarian hyperstimulation syndrome

OBJECTIVE To determine the isolated effect of abdominal paracentesis of ascitic fluid in women with severe OHSS on urine production and blood indices. DESIGN Retrospective interventional study. SETTING Gynecology department at the Lis Maternity Hospital, affiliated to Tel Aviv University. PATIENT(S) Thirty women with severe OHSS. INTERVENTION(S) Abdominal paracentesis according to clinical indications. MAIN OUTCOME MEASURE(S) Urinary output, blood urea nitrogen, as well as a complete blood count were measured before and following the procedure. RESULT(S) Urinary output increased from 1890 +/- 128 mL per 24 hours on the day before paracentesis to 2,660 +/- 226 mL per 24 hours after the procedure. Blood urea nitrogen values were 8.9 +/- 0.56 mg/dL and 7.8 +/- 0.53 mg/dL on the days before and after paracentesis, respectively. White blood cell count decreased from 15.4 +/- 1.1 (x 10(3) cells/mm(3)) on the days before the paracentesis to 13.3 +/- 0.9 (x 10(3) cells/mm(3)) after the procedure. Hematocrit was reduced significantly from 35.2 +/- 1.0% before the paracentesis to 33.4 +/- 0.8% after paracentesis. CONCLUSION(S) Paracentesis of ascitic fluids in women with severe OHSS has an isolated effect in improving renal function, as is evident by the increased urinary output and reduced blood urea nitrogen.