William R. Crombleholme

Risk factors for prematurity and premature rupture of membranes a prospective study of the vaginal flora in pregnancy

Prematurity remains a major cause of perinatal mortality in the United States. Some research has indicated that infectious agents play a role in either initiating preterm labor, causing premature rupture of the membranes, or preventing tocolysis. This study attempted to determine if the presence of various vaginal pathogens in early pregnancy was associated with the subsequent development of premature rupture of membranes or preterm labor. We found that among 233 evaluable patients those with Trichomonas vaginalis were significantly more likely to have premature rupture of the membranes (p less than 0.03), and those with Bacteroides sp. were more likely to be delivered of their infants before 37 weeks (p less than 0.03) and to have infants weighing less than 2500 gm (p less than 0.05). Those with Ureaplasma urealyticum more frequently began preterm labor (p less than 0.05). Preterm premature rupture of the membranes was found significantly more often among patients with Bacteroides sp. Stepwise multiple logistic regression analysis indicated that those associations were not related to the number of previous abortions, deliveries, or preterm deliveries or to maternal age. We conclude that microbiologic screening in early pregnancy may aid in the assessment of patient risk for preterm delivery.

High plasma cellular fibronectin levels correlate with biochemical and clinical features of preeclampsia but cannot be attributed to hypertension alone.

Current concepts of the pathogenesis of preeclampsia involve the generalized dysfunction of maternal vascular endothelial cells. We measured the endothelial isoform of fibronectin as a marker of endothelial cell injury throughout pregnancy in a prospective, case-control study. Nineteen women met strict criteria for the diagnosis of preeclampsia. Nineteen normal pregnant women, and 19 women with gestational hypertension but without other stigmata of preeclampsia (transient hypertension) were selected from the same cohort and matched according to race, age, nulliparity, and gestational age at delivery. Plasma levels of cellular fibronectin were significantly elevated in women meeting strict clinical and biochemical criteria for preeclampsia but not in women with normal pregnancies or transient hypertension. Moderate but significant elevations in mean levels were found in the second trimester in women destined to have preeclampsia, as compared with matched normal and transient hypertension groups (p less than 0.05). The results indicate that elevated plasma levels of cellular fibronectin are not simply the result of increased blood pressure but reflect a maternal insult specific to the syndrome of preeclampsia. Elevation of the mean concentration during the midtrimester is consistent with the hypothesis that endothelial cell injury is a specific lesion that occurs early in the course of preeclampsia, before clinical signs and symptoms.

Parturients Infected with Human Immunodeficiency Virus and Regional Anesthesia Clinical and Immunologic Response

Background It is estimated that 1.5 million Americans are infected with the human immunodeficiency virus (HIV‐1), and the consequences of HIV infection are a leading cause of death in women aged 15–44 yr. Thus, HIV‐1 disease, or acquired immunodeficiency syndrome, occurs with increasing frequency in the parturient, and there is little information concerning the risks of regional anesthesia. Fear of spreading infection to the central nervous system or adverse neurologic sequelae have led some clinicians to advise against regional anesthesia. Thus, this study was undertaken to evaluate the possible problems or risks associated with regional anesthesia in parturients infected with HIV‐1 and to determine whether anesthesia affected the clinical course of the disease. Methods The clinical course and immunologic function of 30 parturients infected with HIV‐1 were evaluated prospectively. Extensive medical and laboratory evaluation before delivery and 4–6 months postpartum was undertaken. Medical problems related to HIV‐1 disease and use of antiviral drugs also were monitored. The anesthetic management was dictated by the clinical situation and the patients wishes with careful postpartum follow‐up to evaluate possible neurologic changes or infection. Results Regional anesthesia was administered in 18 parturients, and 12 received small doses of opioids or no analgesia. There were no changes in the immunologic parameters studied (CD4 sup + p24, beta sub 2 microglobulins), and HIV‐1 disease remained stable in the peripartum period. There were no infections, complications, or neurologic changes in the peripartum period. Sixty‐eight percent of the infants were HIV‐l‐negative and, in 21% of infants, the HIV‐1 status was indeterminate (probably negative). Conclusions This prospective study of parturients infected with HIV‐1 demonstrated that regional anesthesia can be performed without adverse sequelae. There were no neurologic or infectious complications related to the obstetric or anesthetic course. The immune function of the parturient was stable in the peripartum period. Although the number of patients studied was small, with careful medical evaluation, regional anesthesia is an acceptable choice in the parturient infected with HIV‐1.

Efficacy of single-agent therapy for the treatment of acute pelvic inflammatory disease with ciprofloxacin

A prospective, randomized, controlled, non-blind clinical trial was conducted to compare the efficacy of monotherapy with ciprofloxacin with that of a combination of clindamycin plus gentamicin in the treatment of patients with acute pelvic inflammatory disease. Pretreatment and post-treatment cervical culture specimens were obtained for Neisseria gonorrhoeae, Chlamydia trachomatis, Mycoplasma hominis, and Ureaplasma urealyticum. Pretreatment and post-treatment endometrial culture specimens were obtained for those organisms plus facultative and anaerobic bacteria. Minimal inhibitory concentrations were determined on all isolates by agar dilution. Clinical resolution of infection was seen in 31 of 33 (94 percent) ciprofloxacin-treated patients compared with 34 of 35 (97 percent) clindamycin/gentamicin-treated patients. N. gonorrhoeae was eradicated in all cases and C. trachomatis in 12 of 13 cases (92 percent). Ciprofloxacin appeared less effective than clindamycin/gentamicin in eradicating bacterial-vaginosis-associated organisms from post-treatment culture specimens obtained from the endometrium. Comparable clinical response was seen with both regimens. The significance of persistent bacterial-vaginosis-associated organisms following ciprofloxacin therapy is unclear. However, since one goal of treatment of pelvic inflammatory disease should be to eliminate organisms from the upper genital tract, ciprofloxacin may not provide optimal single-agent therapy for pelvic inflammatory disease.

Peripartum cocaine use : estimating risk of adverse pregnancy outcome

Pregnancy outcome of 83 patients with a positive urine toxicology screen for cocaine in the third trimester were reviewed. The outcomes of pregnancies complicated by cocaine abuse were compared to those of matched controls selected from our general obstetric population. We observed a statistically significant increase in the incidence of premature separation of the placenta, low birthweight infants, preterm deliveries, and the incidence of fetal distress requiring cesarean section. On admission, 55% of patients denied recent cocaine use. These observations have implications for planning perinatal services.

Ampicillin/sulbactam versus metronidazole-gentamicin in the treatment of soft tissue pelvic infections

The clinical efficacy and safety of ampicillin/sulbactam versus metronidazole-gentamicin were evaluated in a comparative, randomized, prospective study. Forty-four patients were enrolled: 22 received the ampicillin/sulbactam regimen, and 22 received the metronidazole-gentamicin combination. There were 33 cases of severe acute pelvic inflammatory disease, two tuboovarian abscesses, five cases of endomyometritis, and two cases of posthysterectomy pelvic cellulitis. Aerobic and anaerobic cultures from the infection sites yielded 447 microorganisms from 44 patients (an average of 10 bacteria per infection; 6.4 anaerobes and 3.7 aerobes). The most frequent isolates were Bacteroides sp., 54; Bacteroides bivius, 17; black-pigmented Bacteroides, 12; Bacteroides disiens, 11; Fusobacterium, 13; Peptostreptococcus anaerobius, 24; Peptostreptococcus asaccharolyticus, 21; anaerobic gram-positive cocci, 34; Gardnerella vaginalis, 29; Neisseria gonorrhoeae, 17; alpha-hemolytic streptococci, 15; and Escherichia coli, five. Clinical cure was noted in 19 of 20 patients treated with ampicillin/sulbactam and 18 of 21 patients treated with metronidazole-gentamicin. One treatment failure occurred in the ampicillin/sulbactam group in a patient who required antichlamydial therapy and had a complex left adnexal mass consistent with an abscess. The cases of metronidazole-gentamicin failure included two patients initially diagnosed as having tuboovarian abscesses who required a change in antibiotic therapy to control the infections. The third patient had postabortion endomyometritis that did not respond to metronidazole-gentamicin therapy within 48 hours, and required a change of medication. No adverse hematologic, renal, or hepatic effects were noted in either group of patients.

A Screening Test for the Detection of Anti-Hiv-1 IgA in Young Infants

A simple dot blot screening test for anti-HIV-1 IgA in infant sera was developed using recombinant HIV proteins. Ten control infants, 19 uninfected infants of seropositive mothers and 12 HIV culture positive infants were studied at 3 month and 18 month time points. Prior to IgG depletion of the serum samples, 11/12 (92%) of the infected infants, 2/19 (11%) of the uninfected and none of the control infants were anti-HIV IgA positive at 3 months of age. After depletion, no anti-HIV IgA antibodies could be detected in the samples from uninfected infants, whereas the antibodies persisted in all 11 samples from the infected infants, resulting in sensitivity and specificity of 91.7% (95% confidence limits 59.8-99.6%) and 100% (79.1-100%) respectively. The assay might prove useful in the early diagnosis of HIV infection and can be performed at a fraction of the cost of commercially available western blot strips.

Sulbactam/ampicillin in the treatment of acute pelvic inflammatory disease

Acute pelvic inflammatory disease is associated with significant adverse reproductive sequelae. To prevent these serious sequelae, treatment regimens must cover the major etiologic agents which are Neisseria gonorrhoeae, Chlamydia trachomatis, and mixed anaerobic‐aerobic bacteria. This report concerns the prospective evaluation of the efficacy of the combination of sulbactam with ampicillin in patients hospitalized with acute pelvic inflammatory disease. Clinical cure was noted in 33 (94%) of 35 patients and post‐treatment cultures demonstrated eradication of N. gonorrhoeae and C. trachomatis in all cases.

Amoxicillin therapy for Chlamydia trachomatis in pregnancy

For treating Chlamydia trachomatis cervical infection in pregnancy, the Centers for Disease Control guidelines recommend either erythromycin base or erythromycin ethylsuccinate. There is no alternate therapy. Because of compliance problems with erythromycin regimens due to gastrointestinal side effects, such an alternative is needed. For this reason, we compared, in an open trial, the efficacy and patient compliance of amoxicillin (500 mg three times a day for 7 days) with those of erythromycin base (500 mg four times a day for 7 days) in treating C trachomatis cervical infections during pregnancy. In the amoxicillin group, 63 of 64 women (98.4%) had negative cervical cultures after treatment, compared with 55 of 58 women (94.8%) treated with erythromycin base. Vertical transmission to the infants was assessed by culture and/or persistent or rising immunoglobulin G antichlamydial antibody. In the amoxicillin group, 37 of 39 infants (94.9%) had no evidence of chlamydial infection, compared with 32 of 36 infants (88.8%) in the erythromycin group. These differences were not significant. The frequency of side effects was higher with erythromycin base than with amoxicillin (15 versus 8%), although not significantly so. However, the frequency of stopping medication because of side effects was significantly higher with erythromycin base than with amoxicillin (13 versus 2%; P<.006). These results suggest that amoxicillin may be an acceptable alternative treatment for chlamydial infections in pregnancy.

Expression of Select Function Associated Antigens During Pregnancy

Pregnancy has long been associated with alterations in phenotypic and functional characteristics of the immune response. We studied a variety of T lymphocyte subsets defined by specific antigen expression during pregnancy using a fluorescence activated cell sorter (FACS) and fluorescein conjugated monoclonal antibodies. Specifically, we performed a cross-sectional analysis of the peripheral blood mononuclear cells from 20 women in the first trimester, 20 women in the second trimester, 26 women in the third trimester and 20 women at the time of delivery. We analyzed for antibody staining of CD3, CD4, CD25 (IL-2 receptor), T cell receptor (beta chain), T cell receptor (delta chain) and two color staining for CD3/CD18 (LFA-1), CD3/CD56 and CD4/CD45R. There was little change in the numbers of cells staining for these antibodies through the three trimesters and at delivery with the exception of T lymphocytes bearing the LFA-1 antigen which were significantly less in the first trimester (P < 0.05). These data s...