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Biomedical subjects

D H Watts

Publications and source records attributed to D H Watts.

At least 37 records · Page 2Linked to original sources
PubMed1997

The acquisition of herpes simplex virus during pregnancy.

BACKGROUND: The acquisition of genital herpes during pregnancy has been associated with spontaneous abortion, prematurity, and congenital and neonatal herpes. The frequency of seroconversion, maternal symptoms of the disease, and the timing of its greatest effect on the outcome of pregnancy have not been systematically studied. METHODS: We studied 7046 pregnant women whom serologic tests showed to be at risk for herpes simplex virus (HSV) infection. Serum samples obtained at the first prenatal visit, at approximately 16 and 24 weeks, and during labor were tested for antibodies to HSV types 1 and 2 (HSV-1 and HSV-2) by the Western blot assay, and the results were correlated with the occurrence of antenatal genital infections. RESULTS: Ninety-four of the women became seropositive for HSV; 34 of the 94 women (36 percent) had symptoms consistent with herpes infection. Women who were initially seronegative for both HSV-1 and HSV-2 had an estimated chance of seroconversion for either virus of 3.7 percent; those who were initially seropositive only for HSV-1 had an estimated chance of HSV-2 seroconversion of 1.7 percent; and those who were initially HSV-2-seropositive had an estimated chance of zero for acquiring HSV-1 infection. Among the 60 of the 94 pregnancies for which the time of acquisition of HSV infection was known, 30 percent of the infections occurred in the first trimester, 30 percent in the second, and 40 percent in the third. HSV seroconversion completed by the time of labor was not associated with an increase in neonatal morbidity or with any cases of congenital herpes infection. However, among the infants born to nine women who acquired genital HSV infection shortly before labor, neonatal HSV infection occurred in four infants, of whom one died. CONCLUSIONS: Two percent or more of susceptible women acquire HSV infection during pregnancy. Acquisition of infection with seroconversion completed before labor does not appear to affect the outcome of pregnancy, but infection acquired near the time of labor is associated with neonatal herpes and perinatal morbidity.

Adult↗
PubMed1997

Effect of pregnancy and zidovudine therapy on viral load in HIV-1-infected women.

The objective of this study was to determine the effect of pregnancy and zidovudine (ZDV) on viral load in HIV-1 infected women. A prospective nonrandomized cohort study was conducted at a university medical center and affiliated clinic and included 44 HIV-1-seropositive pregnant women seen between June 1991 and September 1995. Twenty-three women initiated ZDV therapy during their pregnancy. Seventeen women did not take antiretrovirals, and four women took ZDV prior to and throughout pregnancy. HIV-1 viral load as determined by quantitative peripheral blood mononuclear cell (PBMC) culture and quantitative plasma RNA levels was measured at various times during pregnancy and in the postpartum period. HIV-1 load, by both infectivity and RNA levels, was relatively low and remained stable during pregnancy and through 6 weeks post partum. Initiation of ZDV therapy during pregnancy did not result in a significant decrease in viral load at delivery when controlling for the effect of pregnancy. In those women who received ZDV therapy only during pregnancy, there was a trend toward an increase in viral load measured by PBMC infectivity 6 months post partum compared with the levels before the initiation of ZDV. Mother-to-child transmission of HIV-1 occurred in one of 27 (4%) ZDV-treated women and in two of 16 (12.5%) untreated women. Among HIV-1-infected pregnant women with low viral levels, HIV-1 plasma RNA and infectivity remained stable during and after gestation. Although these results are based on a relatively small number of women and should be considered preliminary, the lack of significant ZDV-associated diminution in viral levels suggests that the protective effect of ZDV on the mother-to-child transmission of HIV-1 may not be due to the reduction in maternal viral levels but, by inference, may be due to the prevention of HIV-1 reverse transcription in the newborn.

Anti-HIV Agents↗
PubMed1997

Herpes simplex virus seropositivity and reactivation at delivery among pregnant women infected with human immunodeficiency virus-1.

OBJECTIVE: Our purpose was to determine whether pregnant women infected with human immunodeficiency virus-1 have an increased risk of herpes simplex virus-2 seropositivity and herpes simplex virus reactivation at delivery. STUDY DESIGN: Sixty women infected with human immunodeficiency virus and 8408 other patients who were delivered at the University of Washington between 1989 and 1995 had herpes simplex virus serologic determinations at delivery. Genital herpes simplex virus cultures were obtained for 48 (80%) of the human immunodeficiency virus-infected women and 5567 (66%) of the controls. Logistic regression was used to adjust for possible confounding factors. RESULTS: Forty-five (75%) of human immunodeficiency virus-infected women and 2709 (32%) controls were seropositive for herpes simplex virus-2 (p < 0.0001). Eight percent of human immunodeficiency virus-infected women and 2% of controls had herpes simplex virus reactivation in labor (p < 0.05). CONCLUSIONS: Infection with herpes simplex virus-2 is common among pregnant women infected with human immunodeficiency virus. Herpes simplex virus reactivation complicates labor in this group more often than in other obstetric patients. The role of herpes simplex virus in perinatal human immunodeficiency virus transmission warrants further study.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Herpes simplex virus type 2 detection by culture and polymerase chain reaction and relationship to genital symptoms and cervical antibody status during the third trimester of pregnancy.

OBJECTIVES: Our goal was to define the frequency of asymptomatic herpes simplex virus type 2 shedding by culture and polymerase chain reaction and to correlate our findings with cervical anti-herpes simplex virus type 2 immunoglobulin A production. STUDY DESIGN: Women who were seropositive for herpes simplex virus type 2 collected daily genital tract samples during the third trimester for culture and deoxyribonucleic acid quantitation by polymerase chain reaction. Cervical secretions were collected weekly for anti-herpes simplex virus type 2 immunoglobulin A. Asymptomatic shedding by culture versus polymerase chain reaction and anti-herpes simplex virus type 2 immunoglobulin A detection with and without genital shedding were compared by means of McNemar's chi 2 test. RESULTS: Asymptomatic shedding was more frequent by polymerase chain reaction than by culture (13.8% vs 2.3%, p < 0.0001). When cervical anti-herpes simplex virus type 2 immunoglobulin A was present, patients were more likely to have negative results by polymerase chain reaction than positive results (66.7% vs 26.7%, p = 0.001). Anti-herpes simplex virus type 2 immunoglobulin A was detected beyond 37 weeks in only one subject. CONCLUSIONS: Polymerase chain reaction was more sensitive than culture for detecting asymptomatic genital herpes simplex virus. The role of immunoglobulin A in clearing genital herpes simplex virus remains to be determined.

Adult↗
PubMed1997

Analysis of the maternal components of the AIDS clinical trial group 076 zidovudine regimen in the prevention of mother-to-infant transmission of human immunodeficiency virus type 1.

To gain insight into the protective effects of the three components of the zidovudine regimen used in AIDS Clinical Trial Group (ACTG) 076 on mother-to-infant transmission of human immunodeficiency virus (HIV) type 1, 188 zidovudine-treated women and their untreated infants from five HIV-1 obstetric centers were retrospectively studied. The overall rate of mother-to-infant transmission was 12.3% (95% confidence interval [CI], 7.9%-18.0%). When the 38 women with <200 CD4 cells/microL were excluded, the mother-to-infant transmission rate was 8.8% (95% CI, 4.6%-14.8%). This rate compares favorably with the 8.3% transmission in the zidovudine arm of the ACTG 076 study. Apart from low (<200/microL) maternal CD4 cells (P = .016), no factors, including the duration of zidovudine therapy during gestation and intravenous administration of zidovudine during labor, affected the rate of mother-to-infant transmission. These findings suggest that antenatal oral zidovudine may be as effective as antenatal oral plus intravenous zidovudine during labor and the three-component ACTG 076 regimen in decreasing mother-to-infant HIV-1 transmission.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Idiopathic genital ulcers in women infected with human immunodeficiency virus.

A national survey of investigators caring for human immunodeficiency virus (HIV)-infected women was undertaken to describe the clinical presentation of idiopathic genital ulcer disease. Patients with negative syphilis and herpes simplex testing and/or negative genital ulcer biopsy were included in this study. Study participants (n = 29) were generally severely immunocompromised (median CD4 cell count was 50/mm3, and 68% had an acquired immunodeficiency syndrome [AIDS]-defining opportunistic process). Thirty-seven percent had coexistent oral ulcers and 19% had their genital ulcer progress to fistula formation (four rectovaginal and one vaginal-perineal). There was generally a favorable response to topical, systemic, and intralesional steroid treatment. This study suggests that idiopathic or probable aphthous genital ulcers in women have similar clinical characteristics to aphthous oroesophageal ulcers. Although infrequent, these genital ulcers can cause severe morbidity. Further research is warranted to better define the pathophysiology and optimal management.

Adult↗
PubMed1996

Asymptomatic maternal shedding of herpes simplex virus at the onset of labor: relationship to preterm labor.

OBJECTIVE: To determine if fetal growth restriction and prematurity are observed with subclinical shedding of herpes simplex virus (HSV) at the onset of labor. METHODS: Within 48 hours of delivery, cultures were taken from the cervix and external genitalia of 15,923 asymptomatic pregnant women without symptoms or signs of genital HSV infection; results were positive for HSV in 57. Each of these 57 women were compared with a control group composed of the three culture-negative women delivering immediately before and the three delivering immediately after each woman shedding HSV. RESULTS: The median birth weight for infants born to the 57 women with asymptomatic shedding was 3050 g, compared with 3360 g among the 342 women without asymptomatic shedding, a statistically significant difference (P < .002). These differences were due to very low birth weight (LBW) among the five infants of women with subclinical viral shedding secondary to recently acquired primary genital herpes; these five infants had a median gestational age of 33 weeks, compared with 37 weeks for the 14 infants of mothers with nonprimary, first-episode disease and 39 weeks for the 33 infants of women with reactivation disease, also a significant difference (P = .018). CONCLUSIONS: Asymptomatic genital shedding of HSV at the onset of labor because of subclinical primary genital HSV infection is associated with preterm delivery. Women who acquire genital HSV-2 before pregnancy and are shedding subclinically at the onset of labor experience no increase in adverse outcome. Thus, prevention of the prematurity and LBW associated with genital herpes means that acquisition of the infection in late pregnancy must be prevented.

Birth Weight↗
PubMed1996

Bacteremia shortly after placental separation during cesarean delivery.

OBJECTIVE: To assess frequency, risk factors, and microbiology of bacteremia within 15 minutes of placental separation during cesarean delivery. METHODS: Ninety-three women undergoing cesarean delivery after a minimum of 4 hours of labor or ruptured membranes were compared with 26 women not in labor undergoing cesarean. Blood cultures for aerobic and anaerobic bacteria were obtained within 15 minutes of delivery of the placenta and before prophylactic antibiotic administration. Chorioamnionic membranes were also cultured. Demographic, labor, delivery, and postpartum characteristics were abstracted from the medical record. RESULTS: Bacteremia was detected in 13 (11%) of 119 women. Bacteremia occurred in 13 (14%) of 93 women after labor or rupture of membranes compared with zero of 26 women not in labor (P = .02). Isolates included group B streptococcus (n = 5), Gardnerella vaginalis (n = 5), Streptococcus pneumoniae (n = 1), Peptostreptococcus sp (n = 1), and mixed flora of Prevotella bivia, G vaginalis, and viridans streptococci (n = 1). Bacteremia was associated with earlier median gestational age, lower median birth weight, and a positive chorioamnionic membrane culture. After adjustment for gestational age, intrauterine monitoring was also significantly associated with bacteremia. CONCLUSION: Bacteremia was common after labor in this population, especially in preterm deliveries and those with positive chorioamnionic-placental culture. Many of the isolates are capable of causing endocarditis. Appraisal of the risk of bacteremia and the risk of bacterial endocarditis should be made in individual patients to assess the need for antibiotic prophylaxis.

Adult↗
PubMed1995

A comparison between detailed and simple histories in the diagnosis of genital herpes complicating pregnancy.

OBJECTIVE: All women seropositive for herpes simplex virus-2 are at risk for asymptomatic viral shedding at the onset of labor and neonatal transmission of the virus. Unfortunately, only 20% to 35% of seropositive adults give a history consistent with genital herpes. We evaluated whether more detailed questioning during pregnancy might elucidate symptoms predictive of seropositivity and therefore better identify women at risk for herpes simplex virus shedding at delivery. STUDY DESIGN: During pregnancy 201 randomly selected women were asked in-depth questions about recurrent genital symptoms and whether they "currently have or have ever had genital herpes." An assessment was made whether the patient had a history compatible with genital herpes. This assessment and the "yes/no" history of genital herpes obtained by physicians at the initial prenatal visit were both compared with herpes simplex virus serologic studies by Western blot. RESULTS: Of 201 patients interviewed, 177 gave no history of genital herpes. Of these, 30.4% were seropositive for herpes simplex virus-2. Detailed histories on these 177 patients indicated that among the 159 subjects without suggestive symptoms or with somewhat suggestive symptoms the corresponding rates of seropositivity were 28% and 30%. Among the 18 (10.2%) subjects with highly suggestive symptoms, only 50% were seropositive. The positive predictive values for recurrent genital symptoms to predict herpes simplex virus-2 seropositivity ranged from 30% to 57%. CONCLUSION: A detailed history of genital symptoms is no better at identifying an herpes simplex virus-2 seropositive patient than is simply asking if she has ever had genital herpes. Serologic screening is a more accurate method of identifying women with past genital herpes or those who are at risk for acquiring genital herpes during pregnancy.

Adolescent↗
PubMed1995

Analysis of human papillomavirus type 16 variants indicates establishment of persistent infection.

Sequence differences in the noncoding region of the human papillomavirus type 16 (HPV-16) genome were displayed using single-stranded conformational polymorphism (SSCP) analysis of polymerase chain reaction (PCR)-amplified material. Two variants accounted for 50%-70% of all HPV-16 variants from 3 cohorts in Seattle. Seventy subjects who were repeatedly HPV-16 DNA-positive over 2-8 4-monthly visits showed an identical SSCP pattern at every visit. Only 10%-20% of the specimens showed evidence of infection by multiple variants when assessed by SSCP. However, cloning and sequencing of the PCR products revealed a substantially higher proportion of specimens with > 1 variant. Sequencing many clones from each specimen confirmed that 1 major variant seemed to predominate over time, whereas minor variants appeared more transient. These results suggest that HPV-16 establishes a persistent infection in which a single variant predominates: coinfection with addition HPV-16 variants results in a minor population of HPV-16 genomes.

Base Sequence↗
PubMed1993

Characteristics of women in preterm labor associated with elevated C-reactive protein levels.

OBJECTIVE: To evaluate clinical, microbiologic, and histologic findings associated with elevated C-reactive protein levels among women in preterm labor or with preterm premature rupture of the membranes (PROM). METHODS: Obstetric data, serum C-reactive protein levels, and amniotic fluid (AF) and chorioamniotic membrane cultures and histology were obtained on 203 women presenting between 22-34 weeks' gestation in preterm labor or with PROM. RESULTS: Women with C-reactive protein greater than 1.5 mg/dL were more likely to deliver within 7 days of enrollment (54 of 68, 79%) than were women with normal C-reactive protein levels (45 of 135, 33%) (P < .001). The median C-reactive protein levels and association with rapid delivery did not differ between women with intact versus ruptured membranes. Elevated C-reactive protein levels were associated with a positive AF culture among women in preterm labor with intact membranes. To control for confounding by a long interval to delivery, only the group delivering within 7 days was considered for evaluation of C-reactive protein levels and placental and infant outcome. Among women delivering within 7 days, elevated C-reactive protein was associated with the development of clinical chorioamnionitis and with infant death before hospital discharge, but not with a positive membrane culture or histologic chorioamnionitis. CONCLUSIONS: Elevated C-reactive protein appears to be associated with AF infection, delivery within 7 days of admission, and infant death among women delivering preterm, but not with membrane infection or inflammation. Elevated C-reactive protein may be helpful in determining the need for AF culture and in targeting studies of antibiotic therapy among women in preterm labor or with preterm PROM.

Amniotic Fluid↗
PubMed1993

The relationship of amniotic fluid cytokines and preterm delivery, amniotic fluid infection, histologic chorioamnionitis, and chorioamnion infection.

OBJECTIVE: To assess the association between cytokines in the amniotic fluid (AF) and preterm delivery, the isolation of bacteria from the AF or chorioamnion, and histologic chorioamnionitis. METHODS: Fifty afebrile women with intact membranes in preterm labor at or before 34 weeks' gestation underwent amniocentesis. Cytokine levels were measured in AF, and cultures were performed. Placentas were cultured and examined histologically. RESULTS: Thirty-two (64%) of the 50 patients delivered at or before 34 weeks' gestation. Delivery at or before 34 weeks, compared with delivery after 34 weeks, was related to increased levels of interleukin-6 (IL-6) (88 versus 12%; P < .001), interleukin-1 (IL-1) alpha (50 versus 6%; P = .004), IL-1 beta (42 versus 0%; P = .002), and prostaglandin (PG) E2 (66 versus 22%; P = .008). Bacteria were recovered from the AF of nine (18%) of the 50 patients. All of the cytokines with increased levels, plus tumor necrosis factor (TNF)-alpha, were related to bacteria in the AF. Increased IL-6, IL-1 alpha, IL-1 beta, TNF-alpha, and PGE2 were also associated with histologic chorioamnionitis among women who delivered within 1 week of amniocentesis. Elevated cytokine levels were not related to chorioamnion infection. CONCLUSIONS: Elevated AF cytokines and PGE2 predicted delivery before 34 weeks' gestation and delivery within 7 days of the amniocentesis, as well as AF infection and histologic chorioamnionitis. These findings support the hypothesis that infection is one cause of preterm delivery, operating via a mechanism involving induction of cytokine production.

Adult↗
PubMed1992

A survey of zidovudine use in pregnant women with human immunodeficiency virus infection.

BACKGROUND AND METHODS: The expanding indications for zidovudine treatment make it important to elucidate the safety and toxicity of this drug for pregnant women and their fetuses. We asked pediatricians and obstetricians at the AIDS (acquired immunodeficiency syndrome) Clinical Trials Units to report information about pregnant women infected with the human immunodeficiency virus (HIV) who were continuing their pregnancies and had received, or were receiving, zidovudine during gestation. RESULTS: Reports of 43 women were received from 17 institutions. Doses of zidovudine ranged from 300 to 1200 mg per day, and 24 women took the drug for at least two trimesters. There were two reported instances of maternal toxicity (one gastrointestinal and one hematologic). No teratogenic abnormalities occurred in the 12 infants with first-trimester exposure to zidovudine. All the infants, including two sets of twins, were born alive. The 38 singleton infants born at term for whom birth weights were reported had a mean birth weight of 3287 +/- 670 g; two cases of intrauterine growth retardation were reported among the infants delivered at term. Hemoglobin values, which were available for 31 newborns, ranged from 7.0 to 12.4 mmol per liter (11.2 to 20 g per deciliter); 3 of the 7 newborns with hemoglobin values of less than 8.4 mmol per liter (13.5 g per deciliter) were born prematurely. CONCLUSIONS: Zidovudine was well tolerated by the pregnant women and was apparently not associated with malformations in the newborns, premature birth, or fetal distress. No pattern of hematologic toxicity was observed in the newborns, but the anemia and growth retardation seen in a minority of the infants could, in part, have resulted from their mothers' treatment with zidovudine.

Abnormalities, Drug-Induced↗
PubMed1992

The association of occult amniotic fluid infection with gestational age and neonatal outcome among women in preterm labor.

To evaluate the relationships between gestational age, neonatal outcome, and amniotic fluid (AF) bacteria, we obtained AF from women with intact membranes in idiopathic preterm labor. Positive cultures were obtained from 20 (19%) of 105 women. The frequency of positive cultures was inversely related to gestational age: 23-26 weeks, nine of 20; 27-30 weeks, four of 24; and 31-34 weeks, seven of 61 (chi2 for trend, P less than .001). Fusobacterium nucleatum, Bacteroides ureolyticus, and Ureaplasma urealyticum were the most common isolates. Facultative and anaerobic bacteria were more commonly isolated from women at less than 30 weeks' gestation, and Ureaplasma urealyticum was commonly isolated at greater than 30 weeks' gestation. Forty percent of the patients identified as having positive AF facultative and anaerobic cultures by the research laboratory had negative cultures in the clinical laboratory. Clinical characteristics and maternal white blood cell count and differential did not differ between women with and without positive cultures. Elevated C-reactive protein levels and a positive AF Gram stain were the two most sensitive and specific methods to predict positive AF cultures. Women with positive cultures delivered a median of 1.0 day after enrollment, compared with 28.5 days for women with negative cultures. The median gestational age at delivery for women with positive cultures was 27.5 weeks, and the median birth weight was 866 g. Positive AF cultures were associated with respiratory distress syndrome, bronchopulmonary dysplasia, and neonatal death. If occult AF infection among women in preterm labor is a treatable cause of preterm birth, then treatment could markedly reduce both perinatal morbidity and mortality.

Amniotic Fluid↗
PubMed1992

Antiviral agents.

Antiviral agents are less numerous and often more toxic than antibacterial agents. Acyclovir is commonly used for suppression and treatment of recurrent genital herpes simplex virus and may be indicated for pregnant women with disseminated herpes. Zidovudine is indicated for pregnant women with human immunodeficiency virus infection who have low CD4 lymphocyte counts. Ganciclovir, vidarabine, ribavirin, amantadine, didanosine, and foscarnet are rarely indicated in gynecology and are not recommended for use in pregnancy.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Microbiologic causes and neonatal outcomes associated with chorioamnion infection.

Chorioamnion infection is associated with histologic chorioamnionitis and prematurity, but the specific chorioamnion microorganisms associated with histologic chorioamnionitis, prematurity, and poor neonatal outcome have not been identified. Bacteria were recovered from the chorioamnion cultures of 32% of 112 placentas delivered at less than or equal to 34 weeks' gestation and from 19% of 156 placentas delivered at greater than 34 weeks' gestation (odds ratio 2.1; 95% confidence interval 1.1 to 3.8). Chorioamnion bacteria most highly related to both prematurity and histologic chorioamnionitis were group B Streptococcus and Fusobacterium species. Chorioamnion infection with Peptostreptococcus was significantly related only to preterm delivery, and infection with Escherichia coli, Bacteroides, and Ureaplasma were significantly related to histologic chorioamnionitis. Among preterm infants, isolation of bacteria from the chorioamnion was related to an increased risk of neonatal death (rate ratio 3.8; 95% confidence interval 1.4 to 11.6). Bacterial infection of the chorioamnion is related to preterm birth, histologic chorioamnionitis, and neonatal death.

Adolescent↗
PubMed1991

Pharmacokinetic disposition of zidovudine during pregnancy.

Zidovudine pharmacokinetics was determined in three human immunodeficiency virus type 1-seropositive women receiving zidovudine (200 mg orally every 4 h) from 19 to 39 weeks of pregnancy and postpartum. Zidovudine concentrations were measured using high-pressure liquid chromatography, and pharmacokinetic analyses were done using model-independent methods. For the pregnant versus postpartum periods, peak zidovudine levels (mean +/- 1 SD) were 3.9 +/- 1.7 mumol/l versus 4.3 +/- 0.04 mumol/l (P = .56); elimination half-lives were 1.3 +/- 0.6 versus 1.0 +/- 0.3 h (P = .41); areas under the concentration curve were 4.5 +/- 1.0 mumol/l x h and 6.8 +/- 0.5 mumol/l x h (P = .02); apparent total body clearances were 2.5 +/- 0.6 l/h/kg and 1.7 +/- 0.4 l/h/kg (P = .05); and apparent steady state volumes of distribution were 3.9 +/- 1.0 l/kg and 2.6 +/- 0.8 l/kg (P = .07), respectively. Umbilical cord serum levels ranged from 113%-127% of maternal levels. No persistent adverse effects of zidovudine therapy were seen in the three women or their babies.

Adult↗