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Biomedical subjects

G D Wendel

Publications and source records attributed to G D Wendel.

At least 19 recordsLinked to original sources

Acyclovir suppression to prevent recurrent genital herpes at delivery.

OBJECTIVE: To determine if suppressive acyclovir near term decreased the frequency of clinical recurrences at delivery in women with recurrent genital herpes simplex virus (HSV) infection. METHODS: We conducted a prospective, double-blind, randomized trial in 234 women with recurrent genital herpes. Women with genital infection of any frequency were enrolled. Patients received either suppressive oral acyclovir 400 mg three times daily or an identical placebo after 36 weeks' gestation. Clinical lesions were identified, and HSV cultures were obtained at delivery. The frequencies of clinical and subclinical HSV recurrences at delivery were evaluated. RESULTS: Six percent of patients treated with acyclovir, and 14% of patients treated with placebo had clinical HSV at delivery (p = 0.046). No patients in the acyclovir group had positive HSV cultures, compared with 6% of placebo-treated patients (p = 0.029). There was no significant difference in subclinical HSV shedding in the acyclovir group (0%) compared with the placebo-treated group (3%) (p = 0.102). CONCLUSIONS: Suppressive acyclovir therapy significantly decreased the incidence of clinical genital herpes and the overall incidence of HSV excretion at delivery in patients with previous herpes infection.

Acyclovir↗

Fetal syphilis: clinical and laboratory characteristics.

OBJECTIVE: To examine the pathophysiology of fetal syphilis and correlate hematologic, immunologic, and sonographic findings. METHODS: Twenty-four women with untreated syphilis during pregnancy were prospectively identified. Sonography with amniocentesis and percutaneous umbilical blood sampling were performed. Darkfield examination, rabbit infectivity testing, and polymerase chain reaction for detection of Treponema pallidum were performed on amniotic fluid. Hematologic and chemical testing of fetal blood was performed using standard techniques. Fetal antitreponemal IgM was detected by Western blot assay. Maternal syphilis was treated with 2.4 to 4.8 million units of benzathine penicillin G intramuscularly. Neonatal outcomes and signs of congenital syphilis were recorded. RESULTS: Six women had primary, 12 had secondary, and six had early latent syphilis. Sixty-six percent of fetuses (95% confidence interval [CI] 47%, 82%) had either congenital syphilis or detection of Treponema pallidum in amniotic fluid. Sixty-six percent had hepatomegaly, including three fetuses (12.5%, 95% CI 4%, 31%) with ascites. Fetal antitreponemal IgM was detected in three cases. Abnormal liver transaminases were found in 88% (CI 69%, 96%), anemia in 26% (CI 13%, 47%), and thrombocytopenia in 35% (CI 19%, 55%). Maternal treatment was successful in 83% (CI 64%, 93%). Risk of treatment failure was significantly increased when hepatomegaly and ascites were present (P =.01). CONCLUSION: Findings with fetal syphilis are similar to those of neonatal syphilis. We hypothesize that fetal transaminase elevation occurs early in the course of infection; hematologic abnormalities and hydrops occur later. Severity of disease may be associated with risk of treatment failure.

Adult↗

Hepatotoxicity with antiretroviral treatment of pregnant women.

BACKGROUND: Hepatotoxicity in adults with human immunodeficiency virus (HIV) infection has been associated with all classes of antiretroviral drugs and coinfection with hepatitis B and C virus. We treated two HIV-infected pregnant women in whom hepatotoxicity developed after initiating antiretroviral therapy. CASES: The first woman developed icterus, jaundice, hyperbilirubinemia, and elevated serum aminotransferase levels approximately 5 months after beginning combination antiretroviral therapy with zidovudine, lamivudine, and efavirenz. Serum aminotransferase abnormalities improved after discontinuation of antiretroviral medications. The second woman had similar symptoms and laboratory abnormalities 3 months after initiation of zidovudine, lamivudine, and nelfinavir. Despite initial improvement after discontinuing her antiretroviral medications, fulminant hepatic failure developed and she died. Both patients tested negative for hepatitis A, B, and C; Epstein-Barr virus; and cytomegalovirus. There was no history of illicit drug use, alcohol use, or blood transfusions in either case. CONCLUSION: We emphasize the need for careful monitoring for hepatotoxicity after initiation of antiretroviral therapy.

Adult↗

A randomized trial that compared oral cefixime and intramuscular ceftriaxone for the treatment of gonorrhea in pregnancy.

OBJECTIVE: The purpose of this study was to evaluate prospectively the Centers for Disease Control recommendations for the treatment of gonococcal infection in pregnancy. STUDY DESIGN: One hundred sixty-one women who were referred with probable endocervical gonorrhea underwent pretreatment endocervical, anal, and oral cultures for Neisseria gonorrhoeae. The women were randomly assigned to receive ceftriaxone 125 mg intramuscularly or cefixime 400 mg orally. Treatment was open and in a 1:1 distribution. There were 95 evaluable patients. The tests of cure cultures were performed 4 to 10 days after treatment. RESULTS: Eighty-six women (91%) had endocervical infection; 39 women (41%) had anal infection, and 11 women (12%) had pharyngeal infection. Fifty of 95 women (53%) had concomitant endocervical chlamydial infection. The overall efficacy was 91 of 95 subjects (95.8%; 95% CI, 89.6%-98.8%). Ceftriaxone was effective in 41 of 43 cases (95%; 95% CI, 84.2%-99.4%), and cefixime was effective in 50 of 52 cases (96%; 95% CI, 86.8%-99.5%). No significant difference was noted in the overall efficacy or by site of infection. Three of the 4 women who experienced treatment failures admitted to unprotected intercourse before their test of cure culture. CONCLUSION: Both intramuscular ceftriaxone 125 mg and oral cefixime 400 mg appear to be effective for the treatment of gonococcal infection in pregnancy.

Administration, Oral↗

Acyclovir suppression to prevent clinical recurrences at delivery after first episode genital herpes in pregnancy: an open-label trial.

OBJECTIVE: To continue evaluation of the use of acyclovir suppression in late pregnancy after first episode genital herpes simplex virus (HSV) infection, using an open-label study design. METHODS: Ninety-six women diagnosed with genital herpes for the first time in the index pregnancy were prescribed suppressive acyclovir 400 mg orally three times daily from 36 weeks until delivery in an open-label fashion. Herpes cultures were obtained when patients presented for delivery. Vaginal delivery was permitted if no clinical recurrence was present; otherwise a Cesarean delivery was performed. Neonatal HSV cultures were obtained and infants were followed clinically. Rates of clinical and asymptomatic genital herpes recurrences and Cesarean delivery for genital herpes were measured, and 95% confidence intervals were calculated. RESULTS: In 82 patients (85%) compliant with therapy, only 1% had clinical HSV recurrences at delivery. In an intent to treat analysis of the entire cohort, 4% had clinical recurrences (compared with 18-37% in historical controls). Asymptomatic shedding occurred in 1% of women without lesions at delivery. Two of the four clinical recurrences were HSV-culture positive. No significant maternal or fetal side-effects were observed. CONCLUSIONS: In clinical practice the majority of patients are compliant with acyclovir suppression at term. The therapy appears to be effective at reducing clinical recurrences after a first episode of genital herpes complicating a pregnancy.

Acyclovir↗

In vitro selection of lentivirus vector-transduced human CD34+ cells.

Human CD34(+) cells with in vivo repopulating potential hold much promise as a target for corrective gene transfer for numerous hematopoietic disorders. However, the efficient introduction of exogenous genes into this small, quiescent population of cells continues to present a significant challenge. To circumvent the need for high initial transduction efficiency of human hematopoietic cells, we investigated a dominant selection strategy using a variant of the DHFR gene (DHFR(L22Y)). For this purpose, we constructed a lentivirus-based bicistronic vector expressing EGFP and DHFR(L22Y). Here we demonstrate efficient in vitro selection and enrichment of lentivirus vector-transduced human CD34(+) hematopoietic cells from fetal liver, umbilical cord blood, bone marrow, and peripheral blood after cytokine mobilization. Growth of transduced human CD34(+) cells in semisolid culture under selective pressure resulted in enrichment of transduced progenitor cells to 99.5% (n = 14). Selection for DHFR(L22Y)(+) cells after expansion of transduced progenitors in liquid culture resulted in a 7- to 13-fold increase in the percentage of marked cells. Thus we have shown that transduced human hematopoietic cells may be effectively enriched in vitro by dominant selection, suggesting that development of such strategies holds promise for future in vivo application.

Antigens, CD34↗

Risk of hepatitis B transmission after amniocentesis in chronic hepatitis B carriers.

OBJECTIVE: To measure the risk of perinatal transmission of HBV in chronic carriers who undergo amniocentesis. METHODS: This was a prospective, longitudinal study from 1990 to 1995 of women who were HBV carriers and underwent amniocentesis. The infants of these women were followed from birth to one year of age. Maternal data examined included HBV antigen and antibody status, liver function tests (LFTs) and the amniocentesis report. RESULTS: Twenty-eight women were identified. Two of 28 neonates were stillborn unrelated to hepatitis. Five infants were lost to follow-up leaving 21 mother-child pairs to evaluate. All 21 women were chronic HBV carriers at the time of amniocentesis for delivery. No mother had abnormal LFTs, and only one of 21 women was positive for hepatitis B e antigen (HBeAg). Thirteen amniocenteses were for advanced maternal age, and four were for abnormal maternal serum alphafetoprotein (MSAFP) screening. None of the amniocenteses were recorded as bloody, and the placenta was anterior in 6 of 21 procedures. None of the 21 infants (95% CI: 0-16.8%) were positive for HbsAg during the first month of life or at 12 months of age. All infants received HBV vaccine and HBIG immunoprophylaxis. CONCLUSION: The risk of transmission of HBV to the fetus after amniocentesis in women who are HBV carriers is low. Immunoprophylaxis in these infants was successful.

Amniocentesis↗

Efficacy of treatment for syphilis in pregnancy.

OBJECTIVE: To evaluate prospectively the Centers for Disease Control and Prevention (CDC) recommended regimens for the treatment of antepartum syphilis and prevention of congenital syphilis. METHODS: This was a prospective evaluation of recommended syphilis treatment regimens from September 1, 1987, to August 31, 1989, at Parkland Memorial Hospital, Dallas, Texas. Women with syphilis were staged and treated according to CDC recommendations. Treatment included 2.4 million units of intramuscular (IM) benzathine penicillin G for primary, secondary, or early latent (less than 1 year) syphilis. Women with late latent (uncertain or longer than 1 year) syphilis were treated with 7.2 million units of benzathine penicillin G IM over 3 weeks. RESULTS: During the study period, 448 of 28,552 women (1.6%) delivered were diagnosed with syphilis. One hundred eight were diagnosed at delivery and treated postpartum. The remaining 340 (75.9%) gravidas with untreated syphilis attending prenatal clinic comprised the study group. The success of therapy in preventing congenital syphilis was as follows: primary syphilis, 27 of 27; secondary syphilis, 71 of 75; early latent syphilis, 100 of 102; and late latent syphilis, 136 of 136. The success rate for all stages of syphilis was 334 of 340 (98.2%). The success rate of therapy in secondary syphilis was significantly different from that of the other groups (P = .03). Two of the six fetal treatment failures produced preterm stillborns. Only one maternal treatment failure occurred, in a human immunodeficiency virus-infected woman. CONCLUSION: The CDC-recommended regimens for the prevention of congenital syphilis and treatment of maternal infection are effective, but the highest risk of fetal treatment failure exists with maternal secondary syphilis.

Adult↗

Pituitary gland gumma in congenital syphilis after failed maternal treatment: a case report.

A preterm, very low birth weight infant was born to a mother with early latent syphilis who was treated 10 days and 3 days before delivery with 2.4 mU of benzathine penicillin. The infant had clinical, laboratory, and radiographic abnormalities consistent with congenital syphilis, ie, a Venereal Disease Research Laboratory test titer that was fourfold greater than was the maternal titer, hepatosplenomegaly, abnormal liver function tests, pneumonitis, osteochondritis of the long bones, and cerebrospinal fluid (CSF) examination showing a reactive Venereal Disease Research Laboratory test, pleocytosis, and elevated protein content. The infant died on the third day of life, and an autopsy revealed an evolving gumma of the anterior pituitary. Immunoglobulin M immunoblotting of serum and CSF was positive, and polymerase chain reaction detected Treponema pallidum DNA in endotracheal aspirate and CSF. This case highlights the pathologic abnormalities observed in congenital syphilis and focuses on the rare finding of an evolving anterior pituitary gumma. Furthermore, it documents the failure of maternal syphilis treatment during the last 4 weeks of pregnancy to cure fetal infection and supports the recommendation that all infants born to mothers with syphilis treated during the last 4 weeks of pregnancy should receive penicillin therapy.

Female↗

Opioid detoxification in pregnancy.

OBJECTIVE: Opioid withdrawal has been associated with poor fetal growth, preterm delivery, and fetal death. We sought to evaluate the safety of antepartum opioid detoxification in selected gravidas. METHODS: Between 1990 and 1996, women with singleton gestations who reported opioid use were offered inpatient detoxification. Predetoxification sonography was performed to confirm gestational age and to exclude fetuses with growth restriction and oligohydramnios. Women with mild withdrawal symptoms were given clonidine initially, and methadone was substituted if symptoms persisted. Objective signs of withdrawal were treated with methadone from the outset. Antenatal testing was performed once gestations reached 24 weeks. Newborns were observed for signs of neonatal abstinence syndrome and were treated as necessary. Obstetric and neonatal outcome data were collected. RESULTS: Thirty-four gravidas elected to undergo opioid detoxification at a mean gestational age of 24 weeks. The median maximum dose of methadone was 20 mg per day (range 10-85 mg), and the median time to detoxification was 12 days (range 3-39 days). Overall, 20 women (59%) successfully underwent detoxification and did not relapse, ten (29%) resumed antenatal opioid use, and four (12%) did not complete detoxification and opted for methadone maintenance. There was no evidence of fetal distress during detoxification, no fetal death, and no delivery before 36 weeks. Fifteen percent of neonates were treated for narcotic withdrawal. CONCLUSION: In selected patients, opioid detoxification can be accomplished safely during pregnancy.

Adult↗

In utero infection with Treponema pallidum in early pregnancy.

Amniocentesis was performed under sonographic guidance in gravidas (< 20 weeks' gestation) with untreated syphilis. Five to ten millilitres of amniotic fluid from each patient was used for rabbit infectivity testing (RIT) and polymerase chain reaction (PCR) to detect amniotic fluid infection with Treponema pallidum. Gravidas were treated with benzathine penicillin G. Newborns were examined for clinical and laboratory signs of congenital syphilis including immunoglobulin M (IgM) antibody to T. pallidum by Western blotting (immunoblotting). Eleven patients were enrolled at a mean gestational age of 16.8 weeks. T. pallidum was recovered from amniotic fluid by RIT in four cases (36 per cent), and PCR was positive in three of the amniotic fluid specimens (27 per cent). There were no false-positive PCR results. None of the newborns had clinical evidence of congenital syphilis and their sera lacked IgM reactivity to T. pallidum antigens by immunoblotting. These findings confirm in utero infection with T. pallidum in continuing early pregnancy and indicate that in utero treponemal infection can be eradicated by maternal treatment.

Adolescent↗

Postpartum endometritis caused by herpes simplex virus.

BACKGROUND: Herpes simplex virus (HSV) is rarely the causative agent of endometritis and is usually found in association with pelvic inflammatory disease. Only one case of postpartum HSV endometritis has been reported. CASES: We describe two cases of herpes simplex postpartum endometritis. Neither patient had genital HSV lesions noted at the time of delivery. The first case developed after a preterm cesarean delivery in an 18-year-old primipara. She had persistent puerperal fever despite broad-spectrum anti-microbial treatment. The second case was a 16-year-old primipara whose vaginal delivery was complicated by severe postpartum endometritis. Vulvar and endometrial cultures were positive for HSV alone in both patients. Both infants died from disseminated HSV infection. CONCLUSION: Herpes simplex virus can cause clinical postpartum endometritis.

Adolescent↗

A randomized placebo-controlled evaluation of terbutaline for external cephalic version.

OBJECTIVE: To evaluate the efficacy of subcutaneous terbutaline therapy on the success rate of external cephalic version in term gestation. METHODS: Women with singleton noncephalic gestations were assigned randomly to receive either terbutaline (0.25 mg) or placebo. Physicians were blinded to the assignment. Fifteen to 30 minutes after the study drug was administered, external cephalic version was attempted. It was discontinued after three attempts, for patient discomfort, for fetal heart rate decelerations, or when successful. Patients were discharged home after the procedure and allowed to enter spontaneous labor. Primary outcomes evaluated included initial success of version, presentation in labor, and route of delivery. RESULTS: One hundred three women were enrolled in the study between January 1994 and June 1995, of whom 52 were assigned to terbutaline and 51 to placebo. External cephalic version was successful in 27 of 52 (52%) women receiving terbutaline compared with 14 of 51 (27%) of those receiving placebo (P = .019). This comparison yielded a relative risk (RR) of 1.9 (95% confidence interval [CI] 1.3, 6.5). Four of the 27 (15%) successful versions in the terbutaline group and three of the 14 (21%) successful versions in the placebo group spontaneously reverted to breech presentation. Ultimately, in labor there were 24 (46%) cephalic presentations in the terbutaline group and 13 (25%) in the placebo group (P = .048, RR 1.84, 95% CI 1.1, 5.8). Cesarean delivery rates were 11 of 41 (27%) for women with successful versions and 58 of 62 (94%) among those with failed versions (P < .001). CONCLUSION: Terbutaline (0.25 mg) administered subcutaneously before an attempted version in women at term with noncephalic presentations significantly increased the initial success rate of version and the rate of cephalic presentations in labor while decreasing the rate of cesarean delivery.

Adult↗

Syphilis in pregnancy.

Syphilis in pregnancy remains a problem despite the availability of adequate diagnostic tests and years of penicillin therapy. During pregnancy, syphilis is compounded by its occurrence among populations that under-use the health care system and by its association with cocaine use and infection with HIV. The potentially devastating effect of syphilis on the fetus and attendant adverse outcomes on the pregnancy continue to make syphilis a global problem of major medical and public health consequences.

Female↗

Acyclovir suppression to prevent cesarean delivery after first-episode genital herpes.

OBJECTIVE: To determine if suppressive acyclovir therapy given to term gravidas experiencing a first episode of genital herpes simplex virus (HSV)-infection during pregnancy decreases the need for cesarean delivery for that indication. METHODS: Forty-six pregnant women with first episodes of genital herpes during pregnancy were randomly assigned to receive oral acyclovir 400 mg or placebo, three times per day, from 36 weeks' gestation until delivery as part of a prospective, double-blind trial. Herpes simplex virus cultures were obtained when patients presented for delivery. Vaginal delivery was permitted if no clinical recurrence was present; otherwise, a cesarean was performed. Neonatal HSV cultures were obtained and infants were followed-up clinically. RESULTS: None of the 21 patients treated with acyclovir and nine of 25 (36%) treated with placebo had clinical evidence of recurrent genital herpes at delivery (odds ratio [OR] 0.04, 95% confidence interval [CI] 0.002-0.745; P = .002). No woman treated with acyclovir had a cesarean for herpes, compared with nine of 25 (36%) of those treated with placebo (OR 0.04, CI 0.002-0.745; P = .002). No patient in either treatment group experienced asymptomatic genital viral shedding at delivery. No neonate had evidence of herpes infection or adverse effects from acyclovir. CONCLUSION: Suppressive acyclovir therapy reduced the need for cesarean for recurrent herpes in women whose first clinical episode of genital HSV occurred during pregnancy. Suppressive acyclovir treatment did not increase asymptomatic viral shedding and was not harmful to the term fetus.

Acyclovir↗

Genital herpes during pregnancy: no lesions, no cesarean.

OBJECTIVE: To determine the effects at our hospital of adoption of the 1988 guidelines recommended by ACOG for management of genital herpes infections during pregnancy. METHODS: Between 1984-1986, 96 pregnancies complicated by active genital herpes were delivered at Parkland Hospital. The outcome of these pregnancies were compared with 217 similar pregnancies managed after implementation of the 1988 ACOG herpes guidelines. RESULTS: Adoption of the 1988 ACOG herpes guidelines resulted in a 37% decrease in the use of cesarean delivery for women with genital herpes infections at our hospital. Most of this decrease was because the new guidelines eliminated the need for a confirmatory negative herpes culture before permitting vaginal delivery. No neonatal herpes infections occurred as a result of implementing the ACOG recommendations. CONCLUSION: The rate of cesarean delivery for women with genital herpes infections during pregnancy declined significantly at our hospital as a result of the adoption of ACOG herpes guidelines, and there were no neonatal consequences, such as increased incidence of neonatal herpes simplex virus infection.

Cesarean Section↗