OBJECTIVE: The transfer of abacavir, a new nucleoside inhibitor, and amprenavir, a new protease inhibitor, used for the treatment of human immunodeficiency virus, has been studied in the ex vivo human placental model. METHODS: The ex vivo human placental model used C14 antipyrine to determine the transport fraction and clearance index of these compounds at both the peak and trough serum concentrations. The clearance index accumulation and tissue concentrations were determined for each drug by high pressure liquid chromatography. RESULTS: The clearance index of abacavir was 0.47 +/- 0.19 and 0.50 +/- 0.07 at peak and trough concentrations, respectively. The clearance index of amprenavir was 0.38 +/- 0.09 and 0.14 +/- 0.08 at peak and trough concentrations, respectively. There was no unusual accumulation of either drug in the media or tissue when the perfusion system was closed. CONCLUSION: Abacavir is the first nucleoside compound studied in the perfusion system with a high clearance index. The transfer of the protease inhibitor amprenavir had a clearance index 2.75 times greater than the clearance index of ritonavir at peak concentration determined in a previous study. At trough concentration the clearance index was much less than at the peak concentration. A similar result was found with ritonavir.
OBJECTIVE: To study maternal and neonatal effects of combination nucleoside analog therapy administered to human immunodeficiency virus (HIV)-infected pregnant women for maternal indications. METHODS: A multicenter, prospective observational study was undertaken at six perinatal centers in the United States and Canada that supported regional referral programs for the treatment of HIV-infected pregnant women. Demographic, laboratory, and pregnancy outcome data were collected for 39 women whose antiretroviral treatment regimens were expanded to include more than one nucleoside analog for maternal indications. The 40 newborns were monitored at pediatric referral centers through at least three months of age to ascertain their HIV infection status. RESULTS: For all 39 women, zidovudine (ZDV) therapy was instituted at 13.4 +/- 8.2 weeks, with a second agent (lamivudine [3TC] in 85% of cases) being added at a mean gestational age of 17.6 weeks. Duration of therapy with two agents was 20.6 +/- 10.4 weeks overall, with no women stopping medications because of side effects or toxicity. No significant changes in maternal laboratory values were seen, except for an increase in mean corpuscular volume, over the course of pregnancy. No clinically significant adverse neonatal outcomes were noted, with all but the three preterm newborns leaving hospital with their mothers. Neonatal anemia (hematocrit < 50%) was seen in 62% of newborns, with no children needing transfusion; mild elevations of liver function tests, primarily aspartate aminotransferase, were noted in 58% of newborns tested, though none were clinically jaundiced. Overall rate of neonatal HIV infection was 2.5% (95% confidence interval: 0.1-13.2%). CONCLUSION: Combination antiretroviral therapy during pregnancy with two nucleoside analogs was well-tolerated by mothers and newborns, with no significant short-term toxicities or side effects noted. Surveillance of exposed newborns' hematologic and liver function appears warranted.
OBJECTIVE: In women undergoing major gynecologic surgery, we wish to determine the frequency and yield of blood culture, urine culture, and chest X-ray evaluation of postoperative fever. METHODS: A retrospective review of 537 consecutive patients undergoing major gynecologic surgery was performed. In patients who developed postoperative fever, it was determined whether blood culture, urine culture, and/or chest X-ray were performed, and, if so, the frequency of positive results was evaluated. RESULTS: Two hundred eleven patients (39%) developed postoperative fever. Blood cultures were obtained in 77 of 211 (37%) febrile patients, urine cultures in 106 of 211 (50%) febrile patients, and chest X-ray in 54 of 211 (26%) febrile patients. Zero of 77 blood cultures were positive, 11 of 106 (10%) urine cultures were positive, and 5 of 54 (9%) chest X-rays were positive. Logistic regression revealed that late onset fever predicted for positive urine cultures and early onset fever and advanced age predicted for pneumonia. Eighty percent of patients with pneumonia were symptomatic. In 92% of patients with postoperative fever, no infections or pathologic process were diagnosed. CONCLUSION: Although postoperative fever is frequently evaluated by blood culture, urine culture, and chest X-ray, evaluation rarely yields positive results.
OBJECTIVE: The purpose of the study was to assess the effects of Escherichia coli STa (heat stable) toxin on isolated human myometrial response to oxytocin. METHODS: One hundred and sixteen muscle strips were obtained from the lower uterine segment of 42 women undergoing cesarean section at term. Amniotic membranes and decidua were excluded. Uterine contractility in response to cumulative doses of E. coli STa toxin was recorded, as well as uterine response to cumulative doses of oxytocin before and after incubation with STa toxin or vehicle. The 50th percentile effective oxytocin concentration (EC50) of muscle strips with and without spontaneous activity before and after the incubation with STa toxin or vehicle was calculated. A paired t test was used for comparison. RESULTS: Muscle strips with and without spontaneous activity responded to cumulative doses of oxytocin before and after the incubation with STa toxin or vehicle. No differences in contraction force, duration, or frequency were noted between the groups (P > 0.05). Furthermore, this toxin was not able to induce uterine contractility when tested alone. CONCLUSIONS: The inability of this toxin to affect myometrial response to oxytocin in this study may be due to the absence of amnion cells, chorion, or decidua. Other possible explanations for the lack of response are discussed.
OBJECTIVE: The purpose of the study is to determine whether the Gram stain method is superior to the clinical criteria for the diagnosis of bacterial vaginosis in low-income pregnant women seen in a resident clinic setting. The clinical criteria is the current diagnostic method employed to diagnose bacterial vaginosis. STUDY DESIGN: In this study, 51 pregnant women with vaginal discharge were prospectively evaluated. All were screened using the clinical criteria, Gram stain method, and culture of the discharge. The modified scoring system instituted by Nugent et al. (J Clin Microbiol 29:297-301, 1991) was employed in reading the Gram stain smears. The clinical criteria were then compared with the Gram stain method. Isolation of moderate to many Gardnerella vaginalis growth by culture was used as the confirmatory finding. RESULTS: Sensitivity of the Gram stain method (91%) was significantly higher than that of the clinical criteria (46%), (sign test P = 0.0023, < 0.01). The Gram stain method also has both a low false-negative (4%) and high negative predictive value (96%), making it an ideal diagnostic test. CONCLUSION: The Gram stain method is a rapid and cost-effective test that is also highly reproducible and readily available in many laboratories. These features make the Gram stain method a more desirable screening procedure for bacterial vaginosis in a clinic population.
OBJECTIVE: To assess the efficacy of single-dose antibiotic prophylaxis against postpartum endomyometritis in high-risk cesarean section patients. DESIGN: Patients were administered one of three single-dose antibiotic regimens following umbilical cord clamping after cesarean section delivery. SETTING: Prospective randomized trial at a university-based hospital. PATIENTS: The study evaluated 293 consenting women undergoing cesarean section who had either experienced labor for a duration of > or = 6 hr or rupture of amniotic membranes. MAIN OUTCOME MEASURES: Development of postpartum endomyometritis. RESULTS: The incidence of postpartum endomyometritis was 7/95 (7.4%) following the ampicillin/sulbactam regimen, 14/98 (14.3%) after the cefazolin regimen, and 11/99 (11.1%) after the cefotetan regimen. There was no significant difference in postpartum infection among the three study arms. In addition, the incidence of endomyometritis in the three single-dose study arms was not higher than previously noted in studies where three doses of antibiotic were administered. CONCLUSION: Single-dose antibiotic prophylaxis should replace the standard triple-dose therapy for uninfected women undergoing cesarean section who are at risk for postoperative endomyometritis. Ampicillin/sulbactam, cefazolin, and cefotetan are all reasonable antibiotic choices for single-dose therapy.
OBJECTIVE: To determine voluntary human immunodeficiency virus (HIV) testing rates and factors influencing testing in a private obstetric practice. METHODS: Antepartum patients were offered HIV testing after completing a self-assessment questionnaire. Perceived risks and demographics were correlated with testing rates. RESULTS: Overall, 348/600 (58%) women consented to HIV testing. In a univariate analysis, patients with "any" perceived risk(s) were more likely to be tested. Single women and those with an at-risk partner(s) or a history of sexually transmitted disease (STD) were more likely to desire testing. These factors remained independently associated with voluntary testing in a multivariate regression model. No patients tested positive for HIV. CONCLUSIONS: In our private obstetric practice, 26% of women perceived themselves at risk for HIV infection, and testing rates depended on the various risks identified. A history of STDs or an at-risk sexual partner were stronger predictors of voluntary testing than was marital status. Focused HIV counseling among pregnant women at relatively low risk for infection may be possible.
OBJECTIVES: To examine the accuracy of a commercial polymerase chain reaction (PCR) test (Amplicor CTR, Roche Diagnostic Systems, Branchburg NJ) for identification of endocervical chlamydial infections through both laboratory evaluation and among a diverse teaching hospital patient population. METHODS: Testing of reliable threshold inocula and reproducibility were carried out using laboratory stock organisms. Paired endocervical samples from patients with a wide range of indications were tested by PCR and an established culture procedure, and discrepant pairs were further analyzed to determine true results. RESULTS: Laboratory evaluation suggested that one copy of target DNA from a viable organism consistently yielded a positive result, and test reproducibility was very good, with an overall coefficient of variation of 15%. Compared to true results in 1,588 paired clinical samples from 1,489 women with a 10% prevalence of infection, the PCR test and culture yielded respective sensitivities of 87.4% and 78.0%, and negative predictive values of 98.6% and 97.6%. Specificity and positive predictive value for both tests were 100%. Cost per specimen was nearly identical at $18.84 and $18.88 respectively. Polymerase inhibitors and organisms lacking target DNA were not found in false-negative PCR samples. CONCLUSION: This commercial PCR test is accurate, cost-competitive, and much faster than culture for diagnosis of endocervical chlamydia infections in our population of intermediate prevalence of chlamydial infection.
Zidovudine was the first agent approved for treatment of HIV disease, and since its widespread availability in 1987, the pharmacokinetic disposition and clinical effects of ZDV have been extensively evaluated. In addition to its utility as a component of a multidrug combination regimen for the treatment of adult and pediatric HIV-1 infection, it is the only agent approved by the FDA for the prevention of mother-to-child HIV-1 transmission. The effectiveness of ZDV for the prevention of mother-to-child HIV-1 transmission has been demonstrated in several studies. The optimal time during gestation to initiate ZDV therapy and the relative importance of the intrapartum and newborn components is the focus of both current interventional and observational studies. Until more information is available from these trials, the combined maternal/newborn ZDV regimen studied in ACTG 076 remains the recommended treatment regimen of choice in the United States.
OBJECTIVE: The aim of this study was to identify human papillomavirus (HPV) in cervical intraepithelial neoplasia (CIN) lesions and to evaluate the persistence of viral DNA after diathermic large loop excision (DLLE) treatment. STUDY DESIGN: Biopsies from 36 patients with low- and high-grade CIN lesions were studied before and after DLLE treatment looking for HPV sequences. DNA was extracted to perform a radioactive polymerase chain reaction (PCR) using GP 5,6 generic primers. PCR products were analyzed by the single-stranded conformational polymorphism (SSCP) which is a simultaneous detection and typing method. Dot-blot hybridization with generic and type-specific biotinylated oligonucleotide probes was applied in some cases. RESULTS: HPV DNA was found in all pretreatment samples, and the viral type was identified in 80% of them, HPV 16 being the most prevalent. The viral type coincided with that detected in the first biopsy in all except one case. Seventy five percent of the patients (27 cases) were negative for CIN at follow up, but 50% of them remained HPV DNA positive. CONCLUSION: DLLE treatment was effective in removing the CIN lesion but not the HPV. This fact points out the need to asses the presence of HPV in DNA during the follow-up, since viral persistence has been considered a high risk factor for recurrence and/or malignant transformation.
INTRODUCTION: Fallopian tube damage and subsequent infertility are common sequelae of upper genital tract infection with Chlamydia trachomatis. This fallopian tube damage is thought to be immune mediated. The 60 kilodalton chlamydial heat shock protein (hsp) may be the key antigen associated with this pathogenic response. Our objective was to study the relationship between antibody response to 60 kilodalton chlamydial hsp and tubal factor infertility (TFI). SUBJECTS AND METHODS: Twenty-three women with TFI and 33 women with male factor infertility (controls) were studied. Tubal factor infertility was defined as infertility for one year with hydrosalpinx or distal tubal occlusion. Patients' sera were tested for antibodies to the chlamydial hsp using an enzyme-linked immunosorbent assay (ELISA). A stepwise logistic regression was performed by each patient's age, race/ethnicity, self-reported history of chlamydia infection, gonorrhea, or pelvic inflammatory disease (PID), history of ectopic pregnancy, and antibodies to the chlamydial hsp. RESULTS: Eighteen of the 23 women with TFI had a positive result on the hsp ELISA (78.6%) versus 23.4% of controls. Risk factors for TFI were a history of PID (P = 0.022), "nonwhite" race (P = 0.004), history of ectopic pregnancy (P = 0.027), and antibodies to the 60 kilodalton chlamydial hsp (P < 0.001). CONCLUSIONS: Antibodies to 60 kilodalton chlamydial hsp are strongly associated with TFI.
OBJECTIVE: Abnormal uterine bleeding is a common and troublesome problem in human immunodeficiency virus (HIV)-infected women. We sought to evaluate endometrial pathology among HIV-infected women requiring hysterectomy to explore if endometritis may be common among these patients. METHODS: We performed a retrospective analysis of uterine pathology specimens obtained from HIV-infected and control patients requiring hysterectomy in two urban hospitals between 1988 and 1997 matched for age, surgical indication, and history of gonadotropin-releasing hormone (GnRH) use. Cases were evaluated for the presence of plasma cells and assigned a grade between 0 and 3. RESULTS: Indications included cervical dysplasia (4), carcinoma in situ (2), abnormal uterine bleeding (3), and adnexal mass (3). Some degree of abnormal uterine bleeding occurred in all cases. Plasma cell endometritis was twice as common in HIV-infected women compared to HIV-negative specimens (11/11 versus 11/22) (P < 0.05). Plasma cell endometritis was also of a higher grade in specimens from HIV-infected women than in controls (P = 0.001). CONCLUSION: Chronic endometritis was common and of a higher grade among HIV-infected women requiring hysterectomy in our series. Diagnosis and treatment of endometritis should be considered in HIV-infected women with uterine bleeding and/or tenderness. We speculate that antiretroviral and/or antimicrobial treatment for endometritis may effectively treat endometritis and eliminate the need for surgery in some HIV-infected women. We suggest that consideration and treatment of endometritis in HIV-1 infected women being evaluated for possible hysterectomy has the potential to reduce costs and morbidity for patients and providers who may be exposed during surgical procedures.
Gentamicin is a widely-used antimicrobial agent for obstetric and gynecologic infections. Renewed excitement in this antibiotic has arisen from recent information supporting less frequent dosing. In this symposium, we will describe the pharmacokinetics of gentamicin and review new information advocating the use of once-daily administration of gentamicin.
OBJECTIVE: The influence of 17-beta-estradiol on the stress response of Candida albicans was studied. METHODS: The survival of clinical isolates of C. albicans treated with 17-beta-estradiol after heat and oxidative stress was measured by viable plate counts. Cellular proteins were analyzed via SDS-PAGE. RESULTS: The heat stress response induced by 17-beta-estradiol in C. albicans grown at 25 degrees C protected the organisms against the lethal temperature of 48.5 degrees C, as shown by viable plate counts. 17-beta-estradiol also enhanced protection of C. albicans against oxidative stress (menadione exposure). SDS-PAGE analysis of cytoplasmic extracts revealed proteins induced by 17-beta-estradiol were similar to those induced by heat. CONCLUSION: 17-beta-estradiol enhances survival of C. albicans under heat and oxidative stresses. The proteins induced by 17-beta-estradiol are probably heat shock proteins. Because heat shock proteins are considered to be virulence factors, 17-beta-estradiol may function to promote in vivo survival.
OBJECTIVES: Candida albicans is known to produce gliotoxin, which has several prominent biological effects, including immunosuppression. Interference with host defenses may arise from the effects of this toxin on leukocyte structure and function. METHODS: Flow cytometric analysis revealed that polymorphonuclear leukocytes (PMN) were more sensitive to gliotoxin than were mononuclear cells. Structural and various functional aspects of PMN exposed to gliotoxin were studied. RESULTS: Gliotoxin at (1 microgram/mL) did not affect the viability but did diminish PMN chemotaxis and reduced their ability to ingest particles. Other functional aberrations included decreased nitroblue tetrazolium dye reduction, decreased superoxide production, and release of lactoferrin suggesting by degranulation. Gliotoxin also affected the ability of PMN to kill Escherichia coli. CONCLUSIONS: This study suggests a previously unrecognized potential virulence factor of C. albicans that could contribute to persistence of yeast colonization or recurrence of symptomatic infection through diminished host resistance.
OBJECTIVE: To evaluate the pharmacokinetics and cost of once-daily dosing with gentamicin in women with postpartum endometritis. METHODS: Gentamicin in a single daily dose of 4.5 mg/kg was administered intravenously to 10 women with postpartum endometritis. Peak and trough gentamicin levels were measured, and nephrotoxicity and clinical ototoxicity were monitored. Pharmacokinetic data were analyzed, and a cost analysis of once-daily gentamicin administration was performed. RESULTS: The mean elimination constant was 0.105 +/- 0.008 L/h, and the mean volume of distribution was 0.34 +/- 0.07 L/kg. Mean peak gentamicin levels exceeded 11 mg/L, and all trough levels were < 0.3 mg/L. Cost savings of 44% were achieved with once-daily dosing of gentamicin, compared with traditional thrice-daily dosing. CONCLUSIONS: Once-daily dosing with gentamicin in women with postpartum endometritis achieves therapeutic peak levels without drug accumulation. Substantial cost savings are realized with this dosing regimen.
OBJECTIVE: The purpose of this study was to determine the utility of serum CA125 determinations in diagnosing acute salpingitis. METHODS: CA125 levels were determined for 34 women with the clinical diagnosis of pelvic inflammatory disease (PID). Acute salpingitis was confirmed laparoscopically in 28 women (82.3%). RESULTS: Twenty patients (71.4%) with laparoscopically confirmed acute salpingitis had CA125 levels greater than 7.5 units, compared with no patients (0/6) with laparoscopically normal tubes (P = 0.002). The degree of elevation of CA125 levels correlated with the severity of tubal inflammation noted at laparoscopy. All patients with levels above 16 units had laparoscopically severe salpingitis. CONCLUSIONS: We conclude that while CA125 levels above 7.5 units may modestly improve the ability of the clinical diagnosis of PID to accurately reflect visually confirmed acute salpingitis, limitations of the test make its clinical utility questionable.
OBJECTIVES: To assess the knowledge of universal precautions for the delivery and operating rooms by residents and students and to evaluate their use of universal precautions. STUDY DESIGN: Obstetrics and gynecology (ob/gyn) residents (n = 30) and students (n = 31) from an inner-city, teaching hospital were polled by anonymous questionnaire to assess their knowledge of the appropriate barrier equipment for certain ob/gyn procedures. To determine actual compliance with universal precautions, 459 ob/gyn procedures were observed. We noted the use of appropriate barrier equipment for each procedure: gloves for pelvic exam and face shields, gowns, gloves, and booties for vaginal delivery, cesarean delivery, and dilation and curettage. The True Epistat statistical software program was used to perform simple regression analysis. RESULTS: Thirty residents (100%) knew the appropriate barrier equipment required for each type of procedure performed. One student (< 1%) did not know that booties were appropriate for the surgical procedures. Rationale for lack of compliance with universal precautions elicited by the questionnaire included time constraints (64%), inconvenience (52%), and presumption that patient was not infected (34%). The observed rate of compliance with universal precautions by participants indicates that individual compliance was inversely related to the years of experience (overall compliance rate of students was 96%; for first-year residents, 92%, second-year residents, 89%, third-year residents, 84%, fourth-year residents, 78%; r = -0.9918, P = 0.0009). CONCLUSIONS: Knowledge regarding universal precautions was nearly 100%, while overall observed compliance was only 89%. Compliance with universal precautions was better among students (96%) than among residents (88%). Compliance with universal precautions was inversely related to years of experience.