William F. O’Brien

Insights from gene arrays on the development and growth regulation of uterine leiomyomata

OBJECTIVE To use microarray analysis as an unbiased approach to identify genes involved in the induction and growth of uterine leiomyomata. DESIGN Screen by arrays for up to 12,000 genes in leiomyoma (L) and control myometrium (M) from nine patients. SETTING University research laboratories. PATIENT(S) Nine patients in the follicular and luteal phases of the menstrual cycle. INTERVENTION(S) mRNA from L and M was converted to biotin-labeled cRNA and hybridized to cDNA oligonucleotide sequences on the arrays. MAIN OUTCOME MEASURE(S) Greater than two-fold change in gene expression between leiomyoma and matched myometrium. RESULT(S) Prominent among the 67 genes overexpressed in L relative to M were dlk or Pref-1, doublecortin, JM27, ionotropic glutamate receptor subunit 2, apolipoprotein E3, IGF2, semaphorin F, myelin proteolipid protein, MEST, frizzled, CRABP II, stromelysin-3, and TGFbeta3. The genes dlk, IGF2, and MEST are paternally expressed imprinted genes, and the others are involved in tissue differentiation and growth. Prominent among the 78 genes down-regulated in L relative to M were alcohol dehydrogenases 1alpha-gamma, tryptase, dermatopontin, thrombospondin, coxsackievirus receptor, nur77, and c-kit. CONCLUSION(S) Arrays offer large-scale screening of mRNA expression, which will help us differentiate between the genes and metabolic pathways necessary for leiomyoma growth and those regulating myometrial contractions.

Effects of raloxifene in a guinea pig model for leiomyomas

OBJECTIVE Chronic exposure of oophorectomized guinea pigs to 17beta-estradiol causes leiomyoma formation. Our aims were to determine whether these leiomyomas can become estradiol independent after exposure to estradiol and if raloxifene inhibits leiomyoma growth when given concomitantly with estradiol. STUDY DESIGN To induce leiomyoma development, 6 oophorectomized animals received two estradiol implants for 140 days. Next, the estradiol implants were replaced with empty implants in 3 animals, whereas the other 3 received 2 new estradiol implants and raloxifene given per os 10 mg/kg per day for 60 days. Tumor size was monitored biweekly by ultrasonography. RESULTS On estradiol removal, abdominal wall leiomyomas regressed within 15 to 30 days; when estradiol implants were reintroduced, leiomyomas redeveloped. Within 30 days on raloxifene, all abdominal leiomyomas (n = 9) regressed as determined by ultrasonography and verified at laparotomy. Serum raloxifene and estradiol levels were 432 +/- 46 pg/mL and 78 +/- 13 pg/mL (mean +/- SEM, n = 3), respectively, after 60 days of treatment. CONCLUSIONS Leiomyomas did not become estradiol independent, even after long exposure to estradiol; ultrasonography allowed frequent, noninvasive assessment of leiomyoma size, and raloxifene rapidly regressed leiomyomas in this animal model.

Group B Streptococcus: Prevention of Early-onset Neonatal Sepsis

Group B streptococcus (GBS) was recognized as a major pathogen of neonatal disease in the 1970s. With a case-fatality rate of 5% to 20%, prevention of GBS neonatal disease has been an ongoing concern. The Centers for Disease Control and Prevention (CDC), and American College of Obstetricians and Gynecologists (ACOG) published guidelines for preventive strategies in 1996. These strategies, either a risk-based or a culture-based program, have been responsible for reduced incidence of GBS-newborn disease from 1.7 to 0.4 per 1000 live births in the years 1993 to 1999. However, there has been considerable variability in practice patterns. Reanalysis now shows that a culture-based prevention strategy provides greater reduction in early-onset neonatal disease than a risk-based protocol. The CDC replacement guidelines of August 2002 recommend culture-based GBS prevention; the risk-based strategy is no longer supported. Continued efforts to eradicate GBS-newborn disease require an understanding of the pathogen, colonization, and transmission, GBS sampling and detection methods, and maternal therapy. Until a reliable vaccination against GBS is developed, prevention of neonatal GBS disease will rely upon intrapartum treatment of maternal carriers. Target Audience: Obstetricians & Gynecologists, Family Physicians Learning Objectives: After completion of this article, the reader will be able to define the pathogen, Streptococcus agalactiae, describe the methods of transmission and detection, and outline the current recommendations for maternal group B streptococcus therapy.

Combination Antimicrobial Prophylaxis for Hysterectomy… Harm without the Benefit?

OBJECTIVE: Data suggest that combination antimicrobial prophylaxis regimens reduce surgical site infections (SSI) following cesarean deliveries. However, combination regimens are associated with increases in postoperative acute kidney injury (AKI) following nongynecologic surgical procedures. A recent meta-analysis noted the lack of highquality data on the adverse effects of prophylaxis regimens in gynecologic procedures. Thus, we sought to compare postoperative outcomes between hysterectomy patients who received single vs combination antimicrobial prophylaxis.

C. difficile Screening for Colonization among Surgical Ward Admissions Is Feasible and Useful

Abstract Background Identification of patients colonized with C. difficile (CDcol) upon admission and initiation of precautions has been shown to decrease hospital-acquired C. difficileinfection (HA-CDI) in a recent study. We implemented a quality improvement program screening new admissions to a surgical service and evaluated risk factors and outcomes associated with CDcol. Methods Prospective cohort of all patients admitted to the surgical wards including ICU over a 6 month period 10/16–4/17. Upon admission, a perirectal swab was sent for C diff PCR. Patients with positive screens were placed on contact precautions. CDcol patients were not treated. Testing for CDI was done as usual practice only in patients with diarrhea. Main outcome was prevalence of CDcol and relationship to HA-CDI. Results Of 708 surgical admissions, 585 (82.6%) patients were screened, 543 were eligible based on first admission; 19 (3.5%) were colonized. Recent surgical hospitalization (OR 13.2, 95% CI 3.4;52.1) and prior CDI (OR 19.5, 95% CI 2.9;127.7) were independent risk factors for CDcol. Antibiotic and PPI use were not associated. Of those with CDcol, 7 developed CDI (36.8%) compared with 5/524 (0.9%) screen negative patients (adj OR 60, 95% CI 12.6;286). CDcol combined with a prior h/o CDI allowed for detection of 8/12 (75%) cases of HA-CDI compared with 3/12 (25%) if only prior history was available. HA-CDI rates on surgical wards after one month post-implementation were 9.3/10,000 bed days of care compared with 12.2 in 2016 and 12.8 in 2015. No delays in bed flow were identified. Conclusion Admission CDcol prevalence was low in our surgical VA population but was strongly associated with development of HA-CDI. Prior CDI was the strongest risk factor for CDcol and HA-CDI. Knowledge of prior CDI and CDcol status identified 75% of patients who developed CDI, 3 times more than knowledge of prior CDI alone. In certain settings, CDcol screening could improve detection and early isolation of potential CDiff spreaders. Implementation required significant support from administration, nursing and the laboratory, and was successful based on screening percentage without impact on bed flow. Impact on facility CDI rates remains to be fully demonstrated. Disclosures All authors: No reported disclosures.