Etiology of genital ulcer disease in Dakar, Senegal, and comparison of PCR and serologic assays for detection of Haemophilus ducreyi

We used PCR assays to determine the etiology of genital ulcers in patients presenting to a sexually transmitted disease clinic in Dakar, Senegal, and evaluated the ability of two PCR tests (groEL and recD) and two serological tests (adsorption enzyme immunoassay [EIA] and lipooligosaccharide [LOS] EIA) to detect current Haemophilus ducreyi infection. We found that in this population, H. ducreyi, T. pallidum, and herpes simplex virus HSV DNA were detected in 56, 15, and 13% of 39 genital ulcer specimens, respectively, and H. ducreyi DNA was detected in 60% (3 of 5) of samples from ulcerated bubos. Among 40 consecutive patients with genital ulcer disease and with sufficient sample for both PCR assays, the recD and groEL H. ducreyi PCR assays were 83% concordant, with the recD PCR assay detecting six (15%) additional positive specimens and the groEL assay detecting one (3%) additional positive specimen. Compared to PCR, the adsorption EIA and LOS EIA tests had sensitivities of 71 and 59% and specificities of 57 and 90%, respectively, for the diagnosis of current H. ducreyi infection. While these differences in specificity could be due either to previous infection with H. ducreyi or to the detection of cross-reacting antibodies, only 6% of patients from a nearby family planning clinic gave a positive reaction in both the adsorption EIA and LOS EIA assays, indicating that cross-reacting antibodies are not prevalent among clinic attendees in this city. Our studies indicate that the adsorption EIA detects both current and past infection, while the LOS EIA assay is more specific for current infection with H. ducreyi in this population.     

Pharmacogenetics of long-term responses to antiretroviral regimens containing Efavirenz and/or Nelfinavir: an Adult Aids Clinical Trials Group Study

BACKGROUND: Efavirenz and nelfinavir are metabolized by cytochrome P-450 (CYP) 2B6 and CYP2C19, respectively, with some involvement by CYP3A. Nelfinavir is a substrate for P-glycoprotein, which is encoded by MDR1. The present study examined associations between genetic variants and long-term responses to treatment. METHODS: Adult AIDS Clinical Trials Group study 384 randomized antiretroviral-naive subjects to receive efavirenz and/or nelfinavir plus 2 nucleoside analogues, with follow-up lasting up to 3 years. Population pharmacokinetics were estimated from a nonlinear mixed-effects model. Polymorphisms in CYP2B6, CYP2C19, CYP3A4, CYP3A5, and MDR1 were characterized. RESULTS: The 504 participants in the genetic study included 340 efavirenz recipients and 348 nelfinavir recipients (184 of the 504 participants received both efavirenz and nelfinavir). Of the participants, 49% were white, 31% were black, and 19% were Hispanic. Plasma exposure to efavirenz and nelfinavir in each population was significantly associated with the polymorphisms CYP2B6 516G-->T and CYP2C19 681G-->A, respectively. Among efavirenz recipients, the MDR1 position 3435 TT genotype was associated with decreased likelihood of virologic failure and decreased emergence of efavirenz-resistant virus but not with plasma efavirenz exposure. Among nelfinavir recipients, a trend toward decreased virologic failure was associated with the polymorphism CYP2C19 681G-->A. CONCLUSIONS: Genetic variants predict plasma exposure to efavirenz and nelfinavir, and they may predict virologic failure and/or emergence of drug-resistant virus. These associations with treatment responses must be validated in other studies.     

Low risk of ureteral obstruction with "deep" (dorsal/posterior) uterosacral ligament suture placement for transvaginal apical suspension

OBJECTIVE: Transvaginal uterosacral ligament fixation (USLF), often called "high" USLF, is associated with a 1.0% to 10.9% ureteral obstruction rate. Anatomic relations and pelvic rotation with positioning imply "high" (cephalad) suture placement may bring sutures closer to the ureter. We examined the ureteral obstruction rate with a "deep" (dorsal/posterior) uterosacral ligament suture placement modification of a standard USLF procedure. STUDY DESIGN: At the University of Massachusetts and Tufts, 411 consecutive patients underwent Mayo culdoplasty utilizing > or = 3 uterosacral sutures placed "deep" bilaterally. Intraoperative cystoscopy was performed. RESULTS: One patient (0.24% [.01%-1.35%]) had ureteral obstruction attributable to USLF. Two had obstruction secondary to concomitant procedures. Compared with previous published series, the odds of ureteral injury secondary to USLF was 4.6 times lower (95% CI 2.31-9.24; P < .0001). CONCLUSION: Placement of USLF sutures "deep" (dorsal/posterior) increases the margin of safety for the ureter and, in this study, decreased the ureteral injury rate nearly 5-fold.