Predicting Preeclampsia with Noninvasive Measures of Endothelial Dysfunction: A Pilot Study.

Objective This study evaluates the assessment of endothelial function and its prediction for preeclampsia among women with high-risk factors. Study Design A prospective cohort study of 107 pregnant women at 20 weeks or greater gestation with risk factors for developing preeclampsia. Endothelial dysfunction was assessed using peripheral arterial tonometry by generating a reactive hyperemia index (RHI) score. An index score of <1.67 was defined as endothelial dysfunction. The primary outcome was preeclampsia. Logistic regression was used to predict preeclampsia from RHI scores, body mass index, gestational age at RHI evaluation, history of preeclampsia, history of pregestational diabetes mellitus, chronic hypertension, and fetal number. A receiver operating characteristic plot was constructed to predict preeclampsia from the RHI score. Results Among 107 women, 99 had interpretable RHI scores. Among those with an abnormal RHI ( n = 61), 17 (28%) developed preeclampsia. Among women with a normal score ( n = 38), six (16%) developed preeclampsia ( p = 0.166). After logistic regression, there was no significant association. A receiver operating characteristic plot also revealed no association between RHI score and preeclampsia. Conclusion An abnormal RHI score using peripheral arterial tonometry indicating endothelial dysfunction was not predictive of developing preeclampsia in this cohort. Future studies are needed to further evaluate this relationship.

Oral diindolylmethane (DIM): pilot evaluation of a nonsurgical treatment for cervical dysplasia.

OBJECTIVE: Standard surgical treatment for CIN may impair fertility generating a need for alternative treatment options. We tested the efficacy and toxicity of oral DIM in the treatment of CIN 2 or 3 lesions. METHODS: Patients with biopsy-proven cervical intraepithelial neoplasia (CIN) 2 or 3 scheduled for loop electrosurgical excision procedure (LEEP) were randomized 2:1 to receive diindolylmethane (DIM) (BioResponse-DIM, BioResponse, Boulder, CO) orally at approximately 2 mg/kg/day for 12 weeks or placebo (defatted rice bran, BioResponse). Subjects were evaluated every 3-4 months for 1 year. Analysis of data up to 1 year was assessed including Pap smear, HPV, colposcopy, biopsy and physical examination were performed at follow-up. Central pathology review confirmed all histology diagnoses. RESULTS: To date, 64 subjects (mean age 28 years, range 18-61) have been enrolled (45 in the DIM arm, 19 in the placebo arm), with 60 available for analysis. Average follow-up was 6 months. At enrollment, 58% were diagnosed with CIN 2 and 42% with CIN 3, 57% of subjects were Caucasian, 15% African American, 12% Hispanic and 17% Asian. During treatment 2 subjects (3%) complained of nausea (grade 2) at the 3- to 4-month visit. No systemic toxicities were observed (normal CBC, LFTs, comprehensive metabolic). Forty-six subjects had biopsies at first follow-up (77%). Twenty-one subjects (47%) in the DIM group had improved CIN with a decrease by 1-2 grades or a normal result. Median time to improvement was 5 months. Improved Pap smear was seen in 49% (22/45) with either a less severe abnormality or normal result. Colposcopy improved in twenty-five subjects in the DIM group (56%). Of these 25 subjects, 21 (84%) had improved colposcopic impression, 13 (52%) had a decrease in involved quadrants and 18 (72%) had a decrease in lesion number. Complete colposcopic response was observed in 4 subjects (9%). Stratifying by level of dysplasia, age, race, HPV status, tobacco use, contraceptive used did not alter the results. At median follow-up of 6 months, 85% of subjects have not required LEEP based on routine clinical triage of improving global assessment. There was no statistically significant difference in any outcome between the DIM and placebo group. CONCLUSION: Oral DIM at 2 mg/kg/day is well tolerated with no significant toxicity. We observed a high rate of clinically significant improvement in confirmed CIN 2 or 3 lesions among both treatment groups in this randomized clinical trial.

Comparison of endometrial aspiration biopsy techniques: specimen adequacy.

OBJECTIVE: To compare adequacy of specimens obtained by 3 different endometrial aspiration biopsy techniques--corkscrew, modified dilatation and curettage (D&C) and a combination of both, with or without povidone-iodine cervical cleansing. STUDY DESIGN: A retrospective chart review of a single group practice using a single endometrial aspiration biopsy device for all 3 techniques. Each attending indicated their method of use with the device. For diagnostic purposes, specimen adequacy was categorized as "satisfactory," "suboptimal" and "insufficient." RESULTS: There were 66 corkscrew, 71 modified D&C and 55 biopsies performed using the combined technique. Mean age was 48; 62.5% were premenopausal and 89% had a normal-sized uterus. Postmenopausal patients were more likely than younger women to have suboptimal or insufficient samples, 27% vs. 11%, respectively. Using the combined technique was better (95%) than the corkscrew alone (77%) for satisfactory specimens. Diagnosis was possible in 90% of specimens. CONCLUSION: The combined technique appears to be better than using either technique alone. Povidone-iodine cervical cleansing is safe but may be unnecessary. Because of the large numbers of endometrial biopsies performed yearly, even a small difference in test characteristics can have significant clinical ramifications.

Decreased breast cancer rates among women with choriocarcinoma.

OBJECTIVE: We hypothesized that exposure to high levels of hCG in women diagnosed with choriocarcinoma would decrease future breast cancer risk. METHODS: We used the Surveillance, Epidemiology, and End Results (SEER) registry limited-use database (1973-2004) to search for placenta tumors (ICD-10 C58), i.e. choriocarcinoma (CC). Demographics were obtained including patient ID, primary site, year of diagnosis, sex, race, DOB, age group and survival months. Patients with initial choriocarcinoma were searched for subsequent breast cancers. The cohort diagnosis with CC and subsequent breast cancers were compared to general population-based rates of breast cancer. RESULTS: A query for CC yielded 646 women between the ages 15 and 54 years. Of the 646 women, 422 were white, 129 African-American, and 95 "other". Total women-years of observation were 7165.3 with two CC patients developing breast cancer yielding a breast cancer incidence rate of 27.9/100,000 women-years. The incidence rate ratio(IRR) of the CC cohort to the general population was 0.21 (95% CI(0.145-0.327); P<0.01). In women with CC under the age of 35 years the breast cancer rate was 34.1/100,000, IRR 0.27 (95% CI(0.182-0.386); P<0.01). Controlling for race, breast cancer rates in whites were 49.3/100,000 (IRR 0.37, P<0.01); in African-American 1.3/100,000 (IRR 0.01, P<0.001); and 2.6/100,000 (IRR 0.03, P<0.001) in "others" compared to the general population. CONCLUSION: Women with prior CC had a 79% reduction in breast cancer risk compared to the general population regardless of age and race. Given the high level of hCG and decreased rate of breast cancer among women with CC, the hypothesis that hCG is protective against breast cancer seems plausible.