Identifying the molecular signature of the interstitial deletion 7q subgroup of uterine leiomyomata using a paired analysis.

Uterine leiomyomata (UL), the most common neoplasm in reproductive-age women, have recurrent cytogenetic abnormalities including interstitial deletion of 7q. To develop a molecular signature, matched del(7q) and non-del(7q) tumors identified by FISH or karyotyping from 11 women were profiled with expression arrays. Our analysis using paired t tests demonstrates this matched design is critical to eliminate the confounding effects of genotype and environment that underlie patient variation. A gene list ordered by genome-wide significance showed enrichment for the 7q22 target region. Modification of the gene list by weighting each sample for percent of del(7q) cells to account for the mosaic nature of these tumors further enhanced the frequency of 7q22 genes. Pathway analysis revealed two of the 19 significant functional networks were associated with development and the most represented pathway was protein ubiquitination, which can influence tumor development by stabilizing oncoproteins and destabilizing tumor suppressor proteins. Array CGH (aCGH) studies determined the only consistent genomic imbalance was deletion of 9.5 megabases from 7q22-7q31.1. Combining the aCGH data with the del(7q) UL mosaicism-weighted expression analysis resulted in a list of genes that are commonly deleted and whose copy number is correlated with significantly decreased expression. These genes include the proliferation inhibitor HPB1, the loss of expression of which has been associated with invasive breast cancer, as well as the mitosis integrity-maintenance tumor suppressor RINT1. This study provides a molecular signature of the del(7q) UL subgroup and will serve as a platform for future studies of tumor pathogenesis.

Neuroimaging in pregnancy: a review of clinical indications and obstetric outcomes.

OBJECTIVE: To determine indications and outcomes of pregnant women requiring neurologic imaging at a tertiary care center. METHODS: We reviewed medical records of women receiving magnetic resonance (MR) head imaging during pregnancy to determine indications for such imaging and their pregnancy outcomes. RESULTS: Between April 2007 and December 2008, 60 pregnant women presented to Brigham and Women's Hospital with severe headache or other acute neurologic complaint and underwent head imaging. Two patients were found to have significant findings considered to be neurologic emergencies: a right thalamic hemorrhage and a subarachnoid hemorrhage. Nine patients had abnormal findings not requiring immediate intervention but deeming further evaluation. Sixteen patients had abnormal findings determined to be incidental and unrelated to their indication for imaging. Thirty-three patients had unremarkable imaging studies. The most common presenting symptoms included headache (70%) and visual disturbances (48%). The most common imaging studies obtained were MR brain without contrast (87%) and MR angiography head without contrast (73%). The majority of patients (96%) delivered in the third trimester without significant complications. CONCLUSIONS: Most women who receive head imaging in pregnancy do not have adverse findings and have good obstetrical outcomes.

Endometrial intraepithelial neoplasia: clinical correlates and outcomes.

OBJECTIVE: To estimate cancer outcome and outcome predictors of women with endometrial intraepithelial neoplasia (EIN). METHODS: Outcomes of women with first diagnosis of EIN ("index biopsy") were determined by follow-up pathology. Patient characteristics were correlated with EIN regression, EIN persistence, and progression to cancer. RESULTS: Fifteen percent (95% confidence interval [CI] 9.8-20.8%, 26 of 177) of index EIN biopsy samples had concurrent cancer. Of the women with cancer-free index EIN biopsy samples and follow-up by hysterectomy or more than 18 months of surveillance, 25% (95% CI 18.4-33.3%, 36 of 142) showed regression, 35% (95% CI 27.4-43.7%, 50 of 142) showed persistence, and 39% (95% CI 31.3-48.0%, 56 of 142) showed progression. Nonwhite ethnicity and progestin treatment reduced cancer outcomes (odds ratio [OR] 0.16, 95% CI 0.03-0.84 and OR 0.24, 95% CI 0.08-0.70, respectively), whereas body mass index greater than 25 increased malignant outcomes (body mass index 25 or higher, OR 3.05, 95% CI 1.10-8.45). CONCLUSION: Endometrial intraepithelial neoplasia confers a high risk of cancer, but individual patient outcomes cannot be predicted. Management should include exclusion of concurrent carcinoma and consideration of hysterectomy.

Comparative evaluation of accuracy of extraction of medication information from narrative physician notes by commercial and academic natural language processing software packages.

Medication information is frequently only found in narrative physician notes. It is now possible to extract medication data from narrative documents using NLP technology. A number of commercial and academic NLP software packages can perform this function. In this paper we report the first comparative evaluation of their accuracy. Evaluation was carried out on 150 notes randomly selected from electronic medical record. NLP software results were compared to manual abstraction of medication data by two independent reviewers. Recall, precision and F-measure for identification of medication names, doses, frequencies, routes and inactive status were computed. For different data categories, recall ranged from 6.6% to 90.6%, and precision from 16.7% to 96.6%. Recall was highest for medication names and lowest for identification of inactive medications; there were no significant differences in precision between data categories. NLP software accuracy improved significantly over the last decade but further improvements are needed, particularly in analysis of complex sentences.