Nitrous Oxide Use for Intrauterine System Placement in Adolescents.

STUDY OBJECTIVE: To evaluate the impact of nitrous oxide on patient-reported pain for placement of intrauterine systems (IUSs) in adolescents STUDY DESIGN: : Prospective observational study SETTING: : IUS placement in an ambulatory clinic compared with placement with nitrous oxide in a hospital-based sedation unit PARTICIPANTS: : English-speaking adolescents aged 12 to 20 presenting to a pediatric and adolescent gynecologist with a medical indication for IUS placement MAIN OUTCOME MEASURES: : Patient-reported procedural pain measured on a visual analog scale 2 minutes post IUS insertion procedure. Secondary outcome measurement of likelihood of recommending an IUS to a peer. RESULTS: Seventy-four patients agreed to participate. Forty-five patients underwent IUS placement in the clinic. Controlling for age, history of dysmenorrhea, and body mass index, a significant time (change in reported pain scores pre- vs post IUS insertion) by treatment (nitrous oxide vs standard of care) interaction was observed for patient-reported pain (b = -29.32 mm, P < 0.01). Patients receiving nitrous oxide were more likely to recommend an intrauterine placement than patients who received the current standard of care for pain management (b = 0.47, P = 0.02) after controlling for age, baseline pain score, and dysmenorrhea history. CONCLUSION: Patient-reported pain was attenuated for patients who received nitrous oxide relative to those who received standard IUS placement. Patient-reported satisfaction was higher for patients who received nitrous oxide relative to those who received standard IUS placement.

Incisional carcinoma of Mullerian Origin: A case report and review of literature.

Primary incisional carcinoma (PIC) is a rare, delayed complication of surgery, usually attributed to the malignant transformation of endometriosis. We report a case of incisional carcinoma with nodal metastases in a 55-year-old woman, 18 years after cesarean section. She underwent extirpative surgery, including hysterectomy and bilateral salpingo-oophorectomy, without intraperitoneal disease identifed. Adjuvant treatment included sandwiched platinum-based chemotherapy (carboplatin and paclitaxel) and radiation. She remains disease-free 8 months after completing therapy. We identified 46 additional reported cases. Of these, >90% had undergone an "endometrium-exposing" surgery, most commonly cesarean section; while no cases followed adnexal-only surgery. The median time between antecedent surgery and presentation was 18 years. At presentation, tumors were often large (median 8 cm), and symptomatic with pain (63%) and/or mass (26%). Serum CA125 levels were commonly, albeit slightly, elevated (median 57U/ml (IQR 22-96, Range 6-1690)). Lymph node metastases were common (35%), with most following a vulvar-type spread pattern (inguinal first). Most patients (63%) were treated with chemotherapy +/- radiation. Approximately 50% of patients recurred promptly (median < 6 months), but long-term survival was reported following combined chemotherapy/radiation. Lymph node metastases portended a shorter disease-free interval, with 73% of cases recurring (median 5 months) despite chemotherapy-based treatment. These data suggest that some incisional carcinomas may result from displacement of healthy endometrium followed by delayed malignant transformation. Chemotherapy-only and radiation-only treatments are attended by modest prognosis. Taken together, these data suggest there is both need and potential avenues for improved prevention, detection, and treatment of this condition.

High Throughput Analyses of Budding Yeast ARSs Reveal New DNA Elements Capable of Conferring Centromere-Independent Plasmid Propagation.

The ability of plasmids to propagate in Saccharomyces cerevisiae has been instrumental in defining eukaryotic chromosomal control elements. Stable propagation demands both plasmid replication, which requires a chromosomal replication origin (i.e., an ARS), and plasmid distribution to dividing cells, which requires either a chromosomal centromere for segregation or a plasmid-partitioning element. While our knowledge of yeast ARSs and centromeres is relatively advanced, we know less about chromosomal regions that can function as plasmid partitioning elements. The Rap1 protein-binding site (RAP1) present in transcriptional silencers and telomeres of budding yeast is a known plasmid-partitioning element that functions to anchor a plasmid to the inner nuclear membrane (INM), which in turn facilitates plasmid distribution to daughter cells. This Rap1-dependent INM-anchoring also has an important chromosomal role in higher-order chromosomal structures that enhance transcriptional silencing and telomere stability. Thus, plasmid partitioning can reflect fundamental features of chromosome structure and biology, yet a systematic screen for plasmid partitioning elements has not been reported. Here, we couple deep sequencing with competitive growth experiments of a plasmid library containing thousands of short ARS fragments to identify new plasmid partitioning elements. Competitive growth experiments were performed with libraries that differed only in terms of the presence or absence of a centromere. Comparisons of the behavior of ARS fragments in the two experiments allowed us to identify sequences that were likely to drive plasmid partitioning. In addition to the silencer RAP1 site, we identified 74 new putative plasmid-partitioning motifs predicted to act as binding sites for DNA binding proteins enriched for roles in negative regulation of gene expression and G2/M-phase associated biology. These data expand our knowledge of chromosomal elements that may function in plasmid partitioning and suggest underlying biological roles shared by such elements.