The relationship between ankle landing kinematics, isokinetic strength, muscle activity, and the prevalence of lower extremity injuries in university-level netball players during a single season.

Background: Safe landing in netball is fundamental. Research on the biomechanics of multidirectional landings is lacking, especially among netball players. Furthermore, few studies reporting the associations between ankle kinematics, isokinetic ankle muscle strength, muscle activities, and injury prevalence in South African netball have been undertaken. Objectives: To determine the relationships between ankle kinematics, kinetics, isokinetic strength, and muscle activity during jump-landing tasks, as well as the prevalence of lower extremity injuries in university-level netball players during a single season. Methods: This cross-sectional repeated-measure study consisted of ten university-level female netball players. The injury prevalence data was collected during the 2022 netball season. The ankle muscle activity, kinematic, and kinetic data were collected during multidirectional single-leg landing and muscle strength was collected from plantar- and dorsiflexion trials. Results: Netball players' ankle strength was generally below average. There was evidence of negative correlations between the ankle range of motion (ROM), isokinetic strength, and muscle activity amplitudes. A lack of evidence prevented the conclusion that lower extremity dominance predisposed players to injury, and that any specific body part was more likely to be injured among netball players. Conclusion: Landing forces and muscle activity are direction-dependent, especially for the dominant limb. Lower extremity strength and neuromuscular control (NMC) across multiple jump-landing directions should be an area of focus for female netball players.

Production of interferons and beta-chemokines by placental trophoblasts of HIV-1-infected women.

OBJECTIVE: The mechanism whereby the placental cells of a human immunodeficiency virus (HIV)-1-infected mother protect the fetus from HIV-1 infection is unclear. Interferons (IFNs) inhibit the replication of viruses by acting at various stages of the life cycle and may play a role in protecting against vertical transmission of HIV-1. In addition the beta-chemokines RANTES (regulated on activation T cell expressed and secreted), macrophage inflammatory protein-1-alpha (MIP-1alpha), and MIP-1beta can block HIV-1 entry into cells by preventing the binding of the macrophage-trophic HIV-1 strains to the coreceptor CCR5. In this study the production of IFNs and beta-chemokines by placental trophoblasts of HIV-1-infected women who were HIV-1 non-transmitters was examined. METHODS: Placental trophoblastic cells were isolated from 29 HIV-1-infected and 10 control subjects. Supernatants of trophoblast cultures were tested for the production of IFNs and beta-chemokines by enzyme linked immunosorbent assay (ELISA). Additionally, HIV-1-gag and IFN-beta transcripts were determined by a semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) assay. RESULTS: All placental trophoblasts of HIV-1-infected women contained HIV-1-gag transcripts. There were no statistical differences in the median constitutive levels of IFN-alpha and IFN-gamma produced by trophoblasts of HIV-1 infected and control subjects. In contrast, trophoblasts of HIV-1-infected women constitutively produced significantly higher levels of IFN-beta protein than trophoblasts of control subjects. Furthermore, the median levels of beta-chemokines produced by trophoblasts of HIV-infected and control women were similar. CONCLUSIONS: Since there was no correlation between the placental HIV load and the production of interferons or beta-chemokines, the role of trophoblast-derived IFNs and beta-chemokines in protecting the fetus from infection with HIV-1 is not clear.

Mode of delivery and postpartum morbidity among HIV-infected women: the women and infants transmission study.

Cesarean delivery before onset of labor and rupture of membranes (i.e., scheduled cesarean delivery) is associated with a lower risk of vertical transmission of HIV. The following a priori hypotheses were tested: among HIV-infected women, scheduled cesarean delivery is associated with a higher risk of postpartum morbidity, longer hospitalization, and a higher risk of rehospitalization than spontaneous vaginal delivery. Postpartum morbidity occurred following 178 of 1,186 (15%) of deliveries during 1990 to 1998 in The Women and Infants Transmission Study. The most commonly reported postpartum morbidity events were: fever without infection, hemorrhage or severe anemia, endometritis, urinary tract infection, and cesarean wound complications. Several time trends were observed: the median duration of ruptured membranes decreased (p < .001), intrapartum antibiotic use increased (p < .001), the median antepartum plasma HIV RNA concentration decreased (p < .001), and the incidence of any postpartum morbidity decreased (p = .02). With spontaneous vaginal delivery as the reference category, both scheduled (odds ratio [OR] = 4.69; 95% confidence interval [95% CI], 2.03-10.84), and nonscheduled (OR, 2.50; 95% CI, 1.24-5.04) cesarean deliveries were associated with fever without infection; with urinary tract infection (OR, 3.79; 95% CI 1.04-13.85; OR, 3.86; 95% CI, 1.55-9.60, respectively), and with any postpartum morbidity (OR, 3.19; 95% CI 1.69-6.00; OR, 4.10; 95% CI, 2.71-6.19, respectively). Nonscheduled cesarean deliveries were more likely to be complicated by endometritis (OR, 6.98; 95% CI, 3.53-13.78). Adjusted ORs relating mode of delivery and each of the outcomes (fever without infection, urinary tract infection, endometritis, and any postpartum morbidity) were similar to unadjusted ORs. Results of this analysis indicate scheduled cesarean delivery is associated with an increased risk of any postpartum morbidity and, specifically, postpartum fever without infection. The potential for postpartum morbidity with scheduled cesarean delivery should be considered in light of possible adverse events associated with other interventions to decrease the risk of vertical transmission of HIV. Counseling of HIV-infected pregnant women regarding scheduled cesarean delivery as a possible intervention to decrease maternal-infant transmission of HIV should include discussion of these results, as well as new data as they become available, regarding the incidence and severity of postpartum morbidity events among HIV-infected women according to mode of delivery.

Virulence factors of Escherichia coli isolated from female reproductive tract infections and neonatal sepsis.

OBJECTIVE: The presence of enterobacteria such as Escherichia coli in the vagina of normal women is not synonymous with infection. However, vaginal E. coli may also cause symptomatic infections. We examined bacterial virulence properties that may promote symptomatic female reproductive tract infections (RTI) and neonatal sepsis. METHODS: E. coli isolated as the causative agent from cases of vaginitis (n = 50), tubo-ovarian abscess (n = 45) and neonatal sepsis (n = 45) was examined for selected phenotypic and genetic virulence properties. Results were compared with the frequency of the same properties among fecal E. coli not associated with disease. RESULTS: A significantly greater proportion of infection E. coli exhibited D-mannose resistant hemagglutination compared with fecal E. coli (p < 0.01). This adherence phenotype was associated with the presence of P fimbriae (pap) genes which were also significantly more prevalent among isolates from all three infection sites (p < 0.01). The majority of pap+ isolates contained the papG3 allele (Class II) regardless of infection type. Increased frequency of Type IC genes among vaginitis and abscess isolates was also noted. No significant differences in frequency of other bacterial adherence genes, fim, sfa, uca (gaf or dra were observed. E. coli associated with vaginitis was significantly more likely to be hemolytic (Hly+) than were fecal isolates (p < 0.05). The Hly+ phenotype was also more prevalent among tubo-ovarian abscess and neonatal sepsis isolates (p < 0.08). CONCLUSIONS: E. coli isolated from female RTI and neonatal sepses possess unique properties that may enhance their virulence. These properties are similar to those associated with other E. coli extra-intestinal infections, indicating that strategies such as vaccination or bacterial interference that may be developed against urinary tract infections (UTI) and other E. coli extra-intestinal infections may also prevent selected female RTI.

Vulvar hypertrophy with lymphedema. A mimicker of aggressive angiomyxoma.

We report the case of a 43-year-old quadriplegic woman with bilateral vulvar enlargement. The clinical impression was labial hypertrophy, but the microscopic features mimicked aggressive angiomyxoma because of the location, hypocellular proliferation of fibroblastic cells in an edematous-myxoid stroma, and vessels with perivascular collagen deposition, which simulated the thick-walled vessels of aggressive angiomyxoma. Since the lesion lacked true thick-walled vessels and contained ectatic tortuous lymphatics, the pathologic interpretation was lymphedema. This vulvar lesion should be recognized to prevent the misdiagnosis of aggressive angiomyxoma.

Risk factors for preterm birth, low birth weight, and intrauterine growth retardation in infants born to HIV-infected pregnant women receiving zidovudine. Pediatric AIDS Clinical Trials Group 185 Team.

OBJECTIVE: To evaluate independent contributions of maternal factors to adverse pregnancy outcomes (APO) in HIV-infected women receiving antiretroviral therapy (ART). DESIGN: Risk factors for preterm birth (< 37 weeks gestation), low birth weight (LBW) (< 2500 g), and intrauterine growth retardation (IUGR) (birth weight < 10th percentile for gestational age) examined in 497 HIV-infected pregnant women enrolled in PACTG 185, a perinatal clinical trial. METHODS: HIV RNA copy number, culture titer, and CD4 lymphocyte counts were measured during pregnancy. Information collected included antenatal use of cigarettes, alcohol, illicit drugs; ART; obstetric history and complications. RESULTS: Eighty-six percent were minority race/ethnicity; 86% received antenatal monotherapy, predominantly zidovudine (ZDV), and 14% received combination antiretrovirals. Preterm birth occurred in 17%, LBW in 13%, IUGR in 6%. Risk of preterm birth was independently associated with prior preterm birth [odds ratio (OR) 3.34; P < 0.001], multiple gestation (OR, 6.02; P = 0.011), antenatal alcohol use (OR, 1.91; P = 0.038), and antenatal diagnosis of genital herpes (OR, 0.24; P = 0.022) or pre-eclampsia (OR, 6.36; P = 0.025). LBW was associated with antenatal diagnosis of genital herpes (OR, 0.08; P = 0.014) and pre-eclampsia (OR, 5.25; P = 0.049), and baseline HIV culture titer (OR, 1.41; P = 0.037). IUGR was associated with multiple gestation (OR, 8.20; P = 0.010), antenatal cigarette use (OR, 3.60; P = 0.008), and pre-eclampsia (OR, 12.90; P = 0.007). Maternal immune status and HIV RNA copy number were not associated with APO. CONCLUSIONS: Risk factors for APO in antiretroviral treated HIV-infected women are similar to those reported for uninfected women. These data suggest that provision of prenatal care and ART may reduce APO.

Synthesis of IFN-gamma by CD8(+) T cells is preserved in HIV-infected women with HPV-related cervical squamous intraepithelial lesions.

OBJECTIVE: The aim of this study was to investigate whether coinfection with HIV affects the synthesis of Th1 and Th2 cytokines by peripheral blood T cells of women infected with human papillomavirus (HPV). METHODS: Cervical swabs and peripheral blood were obtained from women referred for colposcopy. HPV DNA by Digene's hybrid capture assay, HIV RNA by Roche's Amplicor assay, and cytokine synthesis of T-cell subsets by flow cytometry were assessed. HPV-associated cervical and HIV-associated immune deficiency diseases were staged using the Bethesda System and the Centers for Disease Control criteria, respectively. RESULTS: Patients with HIV and/or HPV infections had lower percentages of IL-2(+) and higher percentages of IL-10(+) T cells than healthy women. Furthermore, women with both virus infections (HIV(+)/HPV(+)) had significantly fewer IL-2(+) CD4(+), IFN-gamma(+) CD4(+), and TNF-alpha(+) CD4(+) T cells than women with HPV infection alone (HPV(+)). Whereas HIV(+) and healthy women had similar numbers of IFN-gamma(+) CD8(+) T cells, HPV(+) women had significantly fewer IFN-gamma(+) CD8(+) T cells than healthy women. CONCLUSION: HIV infection adversely affects the synthesis of Th1 cytokines by CD4(+), but not IFN-gamma synthesis by CD8(+) T cells of women with active HPV infection. The increase in IFNgamma(+) CD8(+) T cells, a phenotype consistent with cytotoxic T lymphocytes, may account for the stable HIV disease of the women studied. However, the increase in IFN-gamma(+) CD8(+) T cells is less likely to be HPV-specific as there was a higher incidence of HPV-related cervical SIL in HIV(+)/HPV(+) women compared with HPV(+) women.

Vitamin A deficiency and other nutritional indices during pregnancy in human immunodeficiency virus infection: prevalence, clinical correlates, and outcome. Women and Infants Transmission Study Group.

Vitamin A levels in plasma and other nutritional indices were measured during pregnancy for 449 women enrolled in a multicenter cohort study of mother-to-infant transmission of human immunodeficiency virus type 1 (HIV-1). During the third trimester, 29.6% of the women had low (20 to <30 microg/dL) and 11.1% had very low (<20 microg/dL) vitamin A levels. Vitamin A and body mass index, serum albumin levels, and hemoglobin levels were weakly correlated. After adjustment for other covariates, women with low and very low vitamin A levels before the third trimester were more likely to deliver infants with low birth weight (<2500 g) than were those with higher levels (odds ratio [OR], 4.58; 95% confidence interval [CI], 1.57-13.4; and OR, 6.99; 95% CI, 1.09-45.0, respectively). However, there was no statistically significant association between vitamin A level and mother-to-infant transmission of HIV-1. Anemia and low body mass index before the third trimester were associated with an increased risk of transmission in univariate analyses but not in multivariate analyses.

Obstetric and newborn outcomes in a cohort of HIV-infected pregnant women: a report of the women and infants transmission study.

OBJECTIVE: To determine obstetric and neonatal outcomes in a cohort of HIV-infected pregnant women and to assess whether HIV-related immunosuppression increases the risk of adverse outcomes of pregnancy. METHODS: Between 1989 and 1994, interview, physical examination, laboratory, and medical record data were prospectively collected from HIV-infected pregnant women and on their newborns. Factors associated with adverse pregnancy outcome and HIV disease status were correlated with pregnancy outcome using logistic regression analysis. RESULTS: 634 women delivered after 24 weeks of gestation. Preterm birth, low birth weight, and small-for-gestational-age neonates occurred in 20.5%, 18.9%, and 24.0% of pregnancies, respectively. Factors associated with low birth weight were CD4 percentage <14%, history of adverse pregnancy outcome, pediatric HIV infection, bleeding during pregnancy, and Trichomonas infection. Preterm birth was associated with CD4 percentage <14%, a history of adverse pregnancy outcome, and bleeding during pregnancy. Being small for gestational age was associated with maternal hard drug use during pregnancy, Trichomonas infection, history of adverse pregnancy outcome, and hypertension. CONCLUSIONS: Adverse pregnancy outcomes are common for HIV-infected women and are associated with low maternal CD4 percentage and pediatric HIV infection. Preterm birth, low birth weight, and small-for-gestational-age ranking, however, are also associated with previously recognized sociodemographic and obstetric factors that are not unique to HIV infection.

Efficacy of zidovudine and human immunodeficiency virus (HIV) hyperimmune immunoglobulin for reducing perinatal HIV transmission from HIV-infected women with advanced disease: results of Pediatric AIDS Clinical Trials Group protocol 185.

Pediatric AIDS Clinical Trials Group protocol 185 evaluated whether zidovudine combined with human immunodeficiency virus (HIV) hyperimmune immunoglobulin (HIVIG) infusions administered monthly during pregnancy and to the neonate at birth would significantly lower perinatal HIV transmission compared with treatment with zidovudine and intravenous immunoglobulin (IVIG) without HIV antibody. Subjects had baseline CD4 cell counts /=200/microL) but not with time of zidovudine initiation (5.6% vs. 4.8% if started before vs. during pregnancy; P=. 75). The Kaplan-Meier transmission rate for HIVIG recipients was 4. 1% (95% confidence interval, 1.5%-6.7%) and for IVIG recipients was 6.0% (2.8%-9.1%) (P=.36). The unexpectedly low transmission confirmed that zidovudine prophylaxis is highly effective, even for women with advanced HIV disease and prior zidovudine therapy, although it limited the study's ability to address whether passive immunization diminishes perinatal transmission.

Maternal and perinatal factors related to maternal-infant transmission of HIV-1 in the P2C2 HIV study: the role of EBV shedding. Pediatric Pulmonary and Cardiovascular Complications of Vertically Transmitted HIV-1 Infection (P2C2 HIV) Study Group.

The association of maternal and perinatal factors with mother-infant transmission of HIV-1 was examined in a prospective multicenter cohort of singleton live births to 508 HIV-1-infected women with children of known HIV-1 infection status (91 [18%] HIV-1-infected, 417 [82%] uninfected). From multivariate logistic regression, independent predictors of HIV-1 transmission included maternal CD4 percentage (CD4%) (odds ratio [OR] per 10% increase in CD4% = 0.70; p = .003), ruptured membranes <24 hours (OR = 3.15; p = .02), and maternal bleeding (OR = 2.90; p = .03), whereas maternal zidovudine (ZDV) use was marginally associated (OR = 0.60; p = .08). The associations of maternal urinary cytomegalovirus (CMV) shedding, oropharyngeal Epstein-Barr virus (EBV) shedding, and serology profiles during pregnancy with HIV-1 transmission were examined in the subset of mothers in whom the CMV and EBV measurements were available. Maternal EBV seropositivity, CMV shedding, and CMV seropositivity were 100% (279 of 279), 7% (16 of 229), and 92% (270 of 274), respectively. These rates did not differ between transmitting and nontransmitting mothers. In univariate analyses, maternal EBV shedding was higher among transmitting than nontransmitting mothers (40 of 49 [82%] compared with 154 of 226 [68%]; p = .06) and was independently associated with transmission in multivariate logistic analyses adjusting for CD4%, ruptured membranes, and ZDV use, with an OR of 2.45 (95% confidence interval (CI), 1.03-5.84; p = .04). This permits the conclusion that EBV shedding is associated with maternal-infant HIV-1 transmission, independent of CD4%.

Role of placental cytokines and inflammation in vertical transmission of HIV infection.

In light of new evidence suggesting that maternal human immunodeficiency virus (HIV) infection produces at least a three-fold increase in the number of early spontaneous abortions, it is important to search for factors that may predispose to fetal wastage. Immunological factors are thought to play an important role in permitting the HLA-disparate fetus to continue to term, despite powerful maternal immune forces capable of rejection. In the context of a heightened incidence of spontaneous abortion in HIV infection, evidence is now accumulating that implicates an imbalance in immune factors in contributing to this fetal loss. Soluble immune factors, such as cytokines, have been suggested as contributing agents to recurrent spontaneous abortions. Inflammatory cytokines-interleukin 1beta, interleukin 6 and tumor necrosis factor alpha-have been measured in isolated placental trophoblastic cells in HIV-infected and non-infected pregnant women in an attempt to explore this hypothesis. These inflammatory cytokines and their messenger RNAs were significantly elevated before and after stimulation in HIV-infected women, supporting the belief that HIV-infected women present their fetuses a milieu of imbalanced immune factors capable of contributing to immunological rejection. In addition, these elevated inflammatory cytokine levels may contribute to HIV disease progression in fetuses by virtue of activation of HIV gene transcription factors similar to what has been demonstrated in in vitro systems. We therefore propose that HIV infection in pregnant women produces an altered state of certain soluble immune factors, which in concert with other immune factor abnormalities, such as loss of immune selection in the fetal thymus, predisposes the fetus to advanced HIV infection and possible spontaneous abortion.

Early spontaneous abortions and fetal thymic abnormalities in maternal-to-fetal HIV infection.

The thymus is thought to play a major role in the immunopathogenesis of human immunodeficiency virus (HIV) infection, particularly in maternal-to-fetal HIV transmission. Characteristic lesions of the HIV-infected thymus include a prominent CD4+ CD8+ T lymphocyte depletion at the corticomedullary junction, the region of the thymus where immune selection occurs. At least threefold excess early spontaneous abortions were noted in a cohort of 124 HIV-infected pregnant women. In these 13 abortuses a very high rate (54%) of HIV vertical transmission was documented, with the thymus gland particularly affected. It is possible that the thymic insult in HIV-infected fetuses contributes to immune rejection of the fetus, possibly by an imbalance of maternal and fetal T1- and T2-type cytokines, known to be important in HIV disease progression. We propose, therefore, that the early spontaneous abortions occurring in HIV-infected pregnant women are due, at least in part, to abnormal immune forces created by HIV infection of the thymus.

Inflammatory cytokine expression is correlated with the level of human immunodeficiency virus (HIV) transcripts in HIV-infected placental trophoblastic cells.

The inflammatory cytokines interleukin-1beta (IL-1beta), IL-6, and tumor necrosis factor alpha (TNF-alpha) have been associated with increased human immunodeficiency virus (HIV) expression and enhanced lymphocyte adhesion to trophoblastic cells in experimental systems. To determine if there is a correlation between the expression of these cytokines and the levels of HIV transcripts in trophoblasts of term placentas from HIV-infected women, we studied the placentae of 30 HIV-positive and 13 control gravidae. Twenty-three of the HIV-positive women received zidovudine (ZDV) as prophylaxis against HIV vertical transmission; only one of the seven women who did not receive ZDV was a transmitter, for an overall vertical transmission rate of 3.8%. Cytokine production was measured by enzyme-linked immunosorbent assay in the supernatants of trophoblastic cell cultures. Additionally, cytokine transcripts and HIV gag sequences were determined by a quantitative reverse transcription-PCR assay. In general, trophoblastic cells of HIV-positive placentas expressed significantly higher levels of IL-1beta, IL-6, and TNF-alpha than those of control placentas. All placentas from HIV-positive women expressed HIV gag transcripts at either a low (<156 copies per microg of total RNA) or a high (>156 copies per microg of total RNA) level. There was a statistically significant positive association between the basal level of TNF-alpha production and the level of HIV gag transcripts of HIV-positive placental trophoblastic cells. Nevertheless, these data, coupled with a low transmission rate, would indicate that some other factors, perhaps working in concert with cytokines, are necessary for vertical transmission of HIV from mother to infant.

Vaginal colonization or infection with Candida albicans in human immunodeficiency virus-infected women during pregnancy and during the postpartum period. Women and Infants Transmission Study Group.

We evaluated the relationship between immunologic status and vaginal colonization or infection with Candida albicans for 605 women enrolled in a multicenter, prospective cohort study of mother-to-infant transmission of human immunodeficiency virus type 1 (HIV-1). A low CD4+ lymphocyte level (< 14% vs. > or = 14%, which corresponds to an absolute count of approximately 200 x 10(6)/L) was associated with a two- to fivefold increased likelihood of vaginal colonization (odds ratio [OR], 2.28; 95% confidence interval [CI], 1.01-5.19) and vaginal candidiasis (OR, 3.08; 95% CI, 1.21-7.71) during pregnancy and during the postpartum period (OR, 2.98; 95% CI, 1.51-5.88 and OR, 5.45; 95% CI, 1.73-16.6, respectively). These associations persisted in multivariate logistic regression analyses. No associations with CD8+ lymphocyte levels or CD8+ CD38+ or other lymphocyte subset levels were found after adjustment for CD4+ cell level and other covariates. However, postpartum (but not antepartum) antibiotic use and pregnancy were also associated with vaginal colonization and candidiasis (P < or = .001 for each). Vaginal candidiasis was not associated with an increased risk of mother-to-infant transmission of HIV-1; however, a related, more inclusive variable, clinical vaginitis or vaginosis of any etiology at the last antepartum visit, was associated with mother-to-infant transmission (OR, 1.92; 95% CI, 1.07-3.43). These findings emphasize the complex, multifactorial nature of vaginal candidiasis and highlight the need for safe and effective treatment and prevention strategies for women with advanced HIV infection.

Incidence of premature birth and neonatal respiratory disease in infants of HIV-positive mothers. The Pediatric Pulmonary and Cardiovascular Complications of Vertically Transmitted Human Immunodeficiency Virus Infection Study Group.

OBJECTIVE: We sought to determine the prematurity rate in infants of HIV-positive mothers and to characterize the incidence and severity of neonatal respiratory disease in this population. STUDY DESIGN: From 1990 to 1994, 600 live-born infants of HIV-infected mothers were enrolled prenatally (73%) or postnatally (27%) from five U.S. centers. Logistic regression was used to determine the association of HIV status in the infant with prematurity (< or = 37 weeks), low birth weight (< or = 2.5 kg), and very low birth weight (< or = 1.5 kg) rates. The incidence of respiratory distress syndrome (RDS), bronchopulmonary dysplasia, meconium aspiration syndrome, and neonatal pneumonia was compared with anticipated rates for gestational age and birth weight. RESULTS: Very high rates of prematurity (19%), low birth weight (18.3%), and very low birth weight (3.3%) were found in the infants of HIV-positive mothers; and HIV infection in the infant was associated with younger gestational age. The overall incidence of RDS was 3% (17/600), which coincided with the anticipated rate, after adjusting for prematurity and birth weight. Only five infants (all < or = 1.5 kg) had bronchopulmonary dysplasia, and none required assisted ventilation beyond 14 days. Three term infants had mild meconium aspiration syndrome, and there were no cases of documented neonatal pneumonia. CONCLUSION: Infants born to HIV-positive mothers exhibited high prematurity and low birth weight rates, and the odds of prematurity were higher in infants who were infected with HIV. Despite the high incidence of prematurity and perinatal risk of this population, incidence and severity of neonatal respiratory disease were not higher than would be expected from available neonatal data in populations not exposed to HIV.

Excess intrauterine fetal demise associated with maternal human immunodeficiency virus infection.

A prospective study of transplacental transmission of human immunodeficiency virus (HIV) showed an increased rate of spontaneous fetal demise in HIV-seropositive mothers: 14 losses in 124 pregnancies. HIV was detected in placental and fetal tissues in 7 of 14 by in situ hybridization. The proportion of fetal infection far exceeded the transmission rate of 13% in liveborn babies. No association was seen between fetal transmission and a maternal history of drug abuse or coinfections; mothers with AIDS more often had fetal loss associated with HIV transmission than did asymptomatic mothers. In affected fetuses, HIV was detected in many tissues and was associated with thymic pathology. This suggests that maternal HIV infection increases the risk for pregnancy loss associated with HIV transmission. The possibility that HIV may be fetotoxic, that thymic dysfunction may interfere with pregnancy progression, or that the intrauterine milieu in HIV-seropositive pregnancies may be unfavorable (or a combination of factors) should be considered.

Transport of recombinant human CD4-immunoglobulin G across the human placenta: pharmacokinetics and safety in six mother-infant pairs in AIDS clinical trial group protocol 146.

Recombinant CD4-immunoglobulin G (rCD4-IgG) is a 98-kDa human immunoglobulin-like protein that is produced by fusing the gp120 binding domain of CD4 to the Fc portion of the human IgG1 heavy chain. This hybrid molecule was given to human immunodeficiency virus (HIV)-infected pregnant women at the onset of labor by intravenous bolus at 1 mg/kg of body weight (group A; n = 3) and 1 week prior to and at the onset of labor by the same route and at the same dose (group B; n = 3). In addition to pharmacokinetic studies, safety in the mothers and infants was determined through routine chemistries, hematology, and urinalysis; immunologic and HIV infection statuses in the infants were assessed through lymphocyte cultures, p24 antigen level determination, culture of HIV from plasma, PCR, lymphocyte subset enumeration, quantitative immunoglobulin analysis, and lymphocyte proliferation. Thirty minutes after the rCD4-IgG injection, concentrations in maternal serum were 12 to 23 micrograms/ml. These concentrations declined slowly, with initial and terminal half-lives (mean +/- standard deviation) of 9.95 +/- 3.23 and 47.6 +/- 22.3 h, respectively. Infants were born 2.6 to 46.5 h after rCD4-IgG administration; concentrations of rCD4-IgG in cord blood ranged from 28 to 107 ng/ml. The half-life of rCD4-IgG in infants ranged from 5 to 29 h. These data demonstrate that the transfer of rCD4-IgG from the mother to the fetus is rapid and that newborns do not appear to have any difficulty eliminating rCD4-IgG. No safety concerns in mothers or infants were encountered. Although the study did not address the question of efficacy, none of the infants was HIV type 1 infected 36 months later. In summary, these findings document that bifunctional immune molecules can be transported across the placenta, and this general approach may be used in the future to block vertical transmission of HIV type 1.

Development of wound infection or separation after cesarean delivery. Prospective evaluation of 2,431 cases.

Wound infections are a common surgical complication, often requiring a prolonged hospital stay and leading to increased costs. Over a one-year period, 2,431 patients were followed after cesarean delivery with prompt evaluation and culture of all suspicious wounds. Seventy subjects (2.8%) developed confirmed wound infection, and 42 (1.7%) developed noninfected open surgical wounds. Seven (0.3%) fascial dehiscences were diagnosed, requiring surgical repair. Forty of 63 (64%) infected wounds had positive bacterial cultures, with Staphylococcus epidermidis (29%), Enterococcus faecalis (17%), Staphylococcus aureus (17%), Escherichia coli (11%) and Proteus mirabilis (10%) the most frequent isolates. Only 7 of 42 (17%) noninfected wounds had positive cultures, with only S aureus, S epidermidis and Corynebacterium species isolated. Ninety-five percent of the noninfected wounds had blood or serous collections present. Rupture of membranes lasting longer than six hours, emergency cesarean delivery and morbid obesity were associated with a statistically increased likelihood of the development of infected wounds. Emergency cesarean delivery and morbid obesity, but not prolonged rupture of membranes, were associated with an increased likelihood of the development of noninfected wounds. Therefore, it appears that at least two mechanisms are responsible for the development of postcesarean open wounds: (1) increased amniotic fluid and wound colonization due to prolonged rupture of membranes, resulting in a wound infection containing one or more bacterial species derived from the cervicovaginal flora, and (2) increased exogenous bacterial contamination and flora consistent with skin species or breaks in sterile technique, often accompanying difficult or emergency surgery.

Early detection of HIV in infants: aspects of design and analysis for diagnostic test studies.

OBJECTIVE: To review investigations on the early detection of HIV infection in infants to determine adherence to traditional methods of study design and analysis for evaluating new laboratory tests. DATA SOURCES: A National Library of Medicine (MEDLINE) search was conducted to identify such investigations through 1993. Cited references in identified manuscripts were also considered. The search was restricted to investigations of human subjects and those published in the English language. STUDY SELECTION: Final inclusion criteria included (1) report of the age and human immunodeficiency virus (HIV) infection status of the subjects at the time of the diagnostic testing, and (2) presentation of data allowing confirmation of presented analyses and additional analyses. DATA EXTRACTION: Criteria for judging the investigations included (1) whether the criteria used to determine the positive and negative test results were defined; (2) whether the necessary sample size for the study was calculated; (3) whether the patients studied were representative of the patients to whom the test would be applied; (4) whether a gold standard evaluation was performed; (5) whether the outcomes included in the analyses were independent; (6) whether the test characteristics were properly analyzed; and, (7) whether confidence intervals were presented. DATA SYNTHESIS: An informative presentation of a diagnostic test should include as a minimum the seven criteria listed above. Only 21 of 36 (58%) of the studies incorporated at least three of the criteria. CONCLUSIONS: There is a wide variation in the manner in which investigations of diagnostic tests are conducted and the results reported. Increased awareness and use of standard study designs and analyses will allow the application of metanalyses. Such analyses will help guide the direction taken for finding and establishing early diagnostic procedures for HIV infection at birth or during infancy.