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Biomedical subjects

A Willoughby

Publications and source records attributed to A Willoughby.

At least 19 recordsLinked to original sources

Vertical transmission of human immunodeficiency virus (HIV) infection. Reactivity of maternal sera with glycoprotein 120 and 41 peptides from HIV type 1.

The observation that approximately 70% of HIV-infected pregnant women do not transmit infection vertically suggests that antibody therapy may be effective in the prevention of transmission of HIV infection from mother to child. Currently, there is an incomplete understanding of the processes involved in vertical transmission of HIV infection. The elucidation of the serological basis of maternal immunity as it relates to protection from vertical transmission is the goal of this study. We have screened 20 maternal sera from HIV+ individuals of known vertical transmission status for reactivity with 31 peptides spanning the entire envelope glycoprotein of HIV-1. Of interest was reactivity to regions outside of the V3 loop of gp120. The findings have been examined in relationship to transmission status, as well as to in vitro anti-HIV-1 biological activity. Our results indicate that lack of vertical transmission is correlated with high viral neutralization activity, but not with antisyncytial activity nor with binding to the V3 peptides examined in this study. Also, the transmission group bound to fewer gp41 peptides when compared with the nontransmission group, suggesting that immune responses to gp41 may be important in preventing transmission. These findings may provide insights into the design of passive immunotherapies.

Adult

Clinical utility of HIV-IgA immunoblot assay in the early diagnosis of perinatal HIV infection.

OBJECTIVE: To ascertain the sensitivity, specificity, predictive value, and clinical use of a human immunodeficiency virus (HIV)-IgA immunoblot assay for diagnosing perinatal HIV infection in infants tested at birth to 1 month, 3 months, and 6 months of age. DESIGN: Prospective, longitudinal cohort study of children born to HIV-infected and noninfected women. The HIV-IgA immunoblot assays were performed at birth to 1 month, 3 months, and 6 months of age and compared with the Centers for Disease Control's classification system of HIV infection in the children. Children were followed up for at least 15 months to ensure accuracy of infection status. SETTING: Municipal hospital in central Brooklyn, NY, where the prevalence of HIV infection is high. PATIENTS: Serum samples from 58 children, 22 with documented HIV infection, 18 noninfected children born to seropositive women, and 18 children born to noninfected women, were studied. MAIN OUTCOME MEASURE: Diagnosis of HIV infection using the Centers for Disease Control's classification scheme was compared with diagnosis using the HIV-IgA immunoblot assay for children 6 months of age or younger. RESULTS: The HIV-IgA immunoblot assay yielded negative results at 3 and 6 months of age for all 18 infants born to seronegative women; for the 18 seroreverting, noninfected children born to infected women, the assay yielded negative results at 1 month, 3 months, and 6 months of age. The positive predictive value of the assay was 100%--no false-positive results were identified in the 88 serum samples obtained from noninfected infants. For the HIV-infected children, sensitivity was a function of age: one (5.9%) of 17 infants had an assay that yielded positive results at birth to 1 month of age, 13 (62%) of 21 infants had assays that yielded positive results at 3 months of age, and 17 (77%) of 22 infants had assays that yielded positive results at 6 months of age. The presence or absence of symptoms did not affect the sensitivity. CONCLUSION: The HIV-IgA immunoblot assay can detect a significant proportion of infected children during an early asymptomatic period of their life. This relatively inexpensive, easily standardized assay may allow for institution of therapy before the onset of clinical symptoms.

Female

Prevalence of HIV infection in childbearing women in the United States. Surveillance using newborn blood samples.

A national, population-based survey was initiated in 1988 to measure the prevalence of human immunodeficiency virus (HIV) infection in women giving birth to infants in the United States. Following standardized procedures, residual dried-blood specimens collected on filter paper for newborn metabolic screening were tested anonymously in state public health laboratories for maternal antibody to HIV. As of September 1990, annual survey data were available from 38 states and the District of Columbia. The highest HIV seroprevalence rates were observed in New York (5.8 per 1000), the District of Columbia (5.5 per 1000), New Jersey (4.9 per 1000), and Florida (4.5 per 1000). Nationwide, an estimated 1.5 per 1000 women giving birth to infants in 1989 were infected with HIV. Assuming a perinatal transmission rate of 30%, we estimate that approximately 1800 newborns acquired HIV infection during one 12-month period. Preventing transmission of HIV infection to women and infants is an urgent public health priority.

Anonymous Testing

Hypochloremic metabolic alkalosis from ingestion of a chloride-deficient infant formula: outcome 9 and 10 years later.

In 1978 and 1979 two infant formulas, Neo-Mull-Soy and Cho-Free, were found to be deficient in chloride. The Centers for Disease Control received reports that hypochloremic metabolic alkalosis (HMA) had developed in 141 children as a result of exposure to these formulas. Thirty-five of these children were examined at 9 and 10 years of age and compared with a group of 32 children who were exposed to the chloride-deficient formulas but were not reported to experience HMA and a group of 61 children who received chloride-sufficient soy formulas in infancy. The control children were matched to the HMA children on sex, race, age, and maternal education. Growth characteristics, performance on the Wechsler Intelligence Scale for Children-Revised (WISC-R), the Boston Naming Test, the Rey-Osterrieth Test, the Clinical Evaluation of Language Fundamentals-Revised (CELF-R), and subtests from several other speech and language tests were compared across the groups. After adjustment for family income and the level of the father's education, significantly lower scores were observed in the HMA children on the WISC-R Arithmetic subtest (mean = 10.5) compared with the soy control children (mean = 12.0, P less than .05) and on the WISC-R Coding subtest (mean = 9.0) compared with the soy control children (mean = 10.8, P less than .01). All the WISC-R subtest scores were, however, within the normal range. Although no significant differences occurred on the CELF-R between groups, the risk of an HMA child falling below the range expected for a standard population was increased on the CELF-R Composite Total, Receptive, and Expressive Language scores: risk ratios = 2.14, 2.14, and 3.03 respectively. Significant differences were observed between the children exposed, both HMA and non-HMA children, and the soy control children for behavioral problems as determined by the Achenbach Childhood Behavioral Checklist. It is concluded that as a group, children with documented HMA appear to have recovered from their growth failure and have normal cognitive development. They may, however, be at risk for deficits in language skills that require expressive language abilities.

Alkalosis

Serious infections during pregnancy among women with advanced human immunodeficiency virus infection.

Fifty-six human immunodeficiency virus seropositive-women and 76 human immunodeficiency virus seronegative-women had known CD4 cell values and were followed up throughout pregnancy. The women with seronegative results and the 40 with seropositive results and CD4 (helper cell) counts consistently greater than 300 cells/mm3 had no serious infections during pregnancy. Among the 16 with seropositive results and counts that fell below 300 cells/mm3, three developed opportunistic infections, one had pneumonia, and one had a post-cesarean-section abscess. Human immunodeficiency virus seropositive-women with low CD4 counts are at markedly increased risk of serious infections during pregnancy. The consequences of this for fetal health, pregnancy management, maternal well-being, and human immunodeficiency virus testing policies are discussed.

Acquired Immunodeficiency Syndrome

Prevalence of human immunodeficiency virus and hepatitis B virus in unselected hospital admissions: implications for mandatory testing and universal precautions.

The prevalence of human immunodeficiency virus (HIV) and hepatitis B virus in serial unselected hospital admissions was determined to examine the potential efficacy of a system of universal blood and body fluid precautions versus a system based on selected or unselected screening. Serum was obtained from 616 (97%) of the 636 patients admitted during a 1-month period and interviews were completed on 540. Of the 616, 23 (3.7%) were confirmed positive for HIV, and 12 (2.0%) of 612 for hepatitis B surface antigen. Of 33 infected persons, only 8 were known to be positive on admission and only 22 were in "high-risk" groups; therefore, selective precautions would not have been effective. Mandatory testing would have required 1216 tests to identify 25 infected persons and would leave in doubt the presence of other transmissible diseases. On the basis of these data, it appears that universal precautions are a logical system of infection control.

Communicable Disease Control

Exposure to a chloride-deficient formula during infancy: outcome at ages 9 and 10 years.

A school-based survey of the 1978 to 1979 birth cohort of two metropolitan Washington, DC, counties was conducted to find children who had been exposed to the chloride-deficient formulas Neo-Mull-Soy and Cho-Free during infancy. Children who had ingested other soy formulas that had an adequate chloride content were also found and matched to the exposed children by sex, race, birth weight, the age of the child, the mixed feeding status of the child, and maternal education. One hundred seventy-one of the exposed children and 261 soy control children were given a battery of psychologic tests in their homes to determine whether there had been any effect on intellectual development as a result of exposure to the chloride-deficient formulas. There were no differences in scores between the groups on the Wechsler Intelligence Scale for Children-Revised, the Boston Naming Test, the Rey-Osterrieth Test, or the FAS Verbal Fluency Test. There was no correlation between duration of exclusive exposure to the chloride-deficient formulas and the Wechsler Intelligence Scale for Children-Revised Full-Scale IQ Score (Pearson product-moment r = -.0825, P = .28). These results cannot be extrapolated to exposed children with documented hypochloremic metabolic alkalosis. It is concluded that in children without documented evidence of hypochloremic metabolic alkalosis, exposure to the chloride-deficient formulas Neo-Mull-Soy or Cho-Free during infancy has not resulted in any long-term adverse effects on cognitive development.

Child

Pregnancy outcomes among mothers infected with human immunodeficiency virus and uninfected control subjects.

Between June 26, 1985, and Feb. 24, 1989, 101 seropositive pregnant women and 129 seronegative pregnant women from the same prenatal clinics in Brooklyn and the Bronx were recruited into a prospective study of human immunodeficiency virus infection in pregnant women and their offspring. This report details the course of pregnancy and short-term neonatal outcomes of 91 seropositive women and 126 seronegative women who gave birth during the study period. Seropositive mothers were significantly more likely to have sexually transmitted diseases (17.6% vs 7.1%, p = 0.017) and medical complications (43.0% vs 25%, p = 0.006) during pregnancy. No other obstetric complications (e. g., chorioamnionitis, endometritis, toxemia, or placental problems) were associated with serologic status. After controlling for confounding variables (drug use, tobacco use, age of mother, and clinic), we found that the mother's serologic status was not significantly associated with birth weight, gestational age, head circumference, or Apgar scores among live infants. For example, after adjustment on confounders we found that children born to seropositive mothers weighed about 7 gm more than children of seronegative mothers (95% confidence interval, -180 to 194 gm). We conclude that in this population human immunodeficiency virus infection has little demonstrable impact on the status at birth of live neonates.

Adult

Population-based study of the developmental outcome of children exposed to chloride-deficient infant formula.

In 1978 and 1979 a large number of US children were fed chloride-deficient soy-based infant formula. A representative sample of such children was identified in a southern county through a mailing to the homes of 3639 first- and second-grade children in the public schools. Of the 2329 (64%) who responded, 56 reported use of deficient formula and were invited to have developmental testing by one of four study psychologists at their school. Of the 310 users of other soy formulas, 112 were selected for testing as matched controls on the basis of their sex, feeding history, age, birth weight, and socioeconomic status (as indicated by school attended). After exclusions and refusals, 42 children who used deficient formula and 66 control children were tested using the McCarthy Scales of Children's Abilities. Examiners were unaware of the child's history of formula use. The mean General Cognitive Index was 102.8 in those using deficient formula and 105.4 in controls. After adjustment for demographic differences the children who used chloride-deficient formula were found to average 4.9 points less than the controls (P = .04, 1-tailed). The largest difference was in the Quantitative subscale (P = .005). These data show a statistically significant although small effect of chloride-deficient formula on the long-term developmental outcome of exposed children; however, further study of these results is needed for full confirmation.

Child

Mother-to-infant transmission of human immunodeficiency virus type 1: association with prematurity or low anti-gp120.

In a prospective study of pregnant women infected with human immunodeficiency virus type 1 (HIV-1) in Brooklyn, New York, USA, 16 (29%) of 55 evaluable infants were infected with HIV-1. 9 infants had paediatric acquired immunodeficiency syndrome, 6 had less severe clinical manifestations of HIV-1 infection, and 1 was symptom-free but was seropositive for HIV-1 beyond 15 months of age. The 10 infants born at 37 weeks of gestation or earlier were at higher risk of HIV-1 infection than infants born at 38 weeks of gestation or later (60% vs 22%) but the median age at appearance of disease was approximately 5 months in both groups. The HIV-1 transmission rate was not associated with predelivery levels of maternal T cells, anti-p24, or neutralising antibodies but it was higher, among full-term infants, for those with mothers in the lowest third of the distribution of anti-gp120 levels (53%). On immunoblot, transmitting mothers lacked a gp120 band but not other bands. Protection was not associated with antibody to recombinant peptides from the hypervariable region of the major neutralising gp120 epitope, and the anti-gp120 endpoint dilution titre was similar in transmitting and non-transmitting mothers. Mothers of uninfected full-term infants appear to confer immunological protection against HIV-1 infection of their offspring by way of a high-affinity antibody to a gp120 epitope, whose specificity has importance for vaccine development and possibly perinatal immunotherapy.

Acquired Immunodeficiency Syndrome

Immunosuppression in pregnant women infected with human immunodeficiency virus.

One hundred two pregnant women at high risk of infection with the human immunodeficiency virus (62 who were drug abusers and 40 of Haitian origin) were prospectively examined for immunologic changes during and after pregnancy. Among the 63 human immunodeficiency virus-negative women, levels of CD4+ (helper) cells fell to a nadir at 8 weeks before delivery and rose rapidly just before delivery. The level of CD8+ (cytotoxic/suppressor) cells rose slowly from midpregnancy to delivery. Among the 37 human immunodeficiency virus-positive pregnant women, levels of CD4+ cells fell during pregnancy (except for a transient weak increase just before delivery) and did not recover in the postpartum period. Levels of CD8+ cells were consistently higher in human immunodeficiency virus-positive than human immunodeficiency virus-negative women. Post partum the CD8+ cells in human immunodeficiency virus-negative women stabilized at delivery levels, whereas they increased greatly in human immunodeficiency virus-positive women. The loss of CD4+ cells in human immunodeficiency virus-positive women appeared to be faster during pregnancy than in the postpartum period. These data support the hypothesis that pregnancy may accelerate human immunodeficiency virus-induced depletion of CD4+ cells and increase the risk of acquired immunodeficiency syndrome.

Acquired Immunodeficiency Syndrome

AIDS in women: epidemiology.

Several facts concerning the distribution of AIDS in U.S. female populations are clear. This disease has made significant inroads, in a quantitative sense, into the female segment of our society as documented by AIDS surveillance data, information on pregnant women and parturients, and by screening data from the military. The impact on women in the reproductive years, on the reproductive health of these women, and on the reproductive outcome of their pregnancies is of substantial concern. Monitoring epidemiologic trends in certain groups will require clever and creative strategies like those of Hoff and colleagues. Additional data may be derived from the CDC's Family of Surveys that will examine HIV prevalence in five groups (in addition to the newborn infant survey described above): intravenous drug users, patients admitted to hospitals, sexually transmitted disease clinic patients, women's health and reproductive health clinics, and tuberculosis clinics. It is hoped that the data obtained from these studies, as well as data gathered on college students and Job Corps applicants, will contribute additional information on HIV infection in women. Monitoring the progress of the AIDS epidemic in women will be difficult. Even more difficult will be the effort to respond to the epidemic in the women it most frequently affects: the poor, minority, disenfranchised women who may be involved in illegal activities (drug use, prostitution, illegal immigration) who are not well networked into the medical and social services of our society.

Acquired Immunodeficiency Syndrome

Final report of the United States Department of Health and Human Services Secretary's Work Group on pediatric human immunodeficiency virus infection and disease: content and implications.

Human immunodeficiency virus (HIV) disease is increasing rapidly in the ranks of the leading causes of death among children. It is already the ninth leading cause of death among children 1 to 4 years of age and the seventh in young people between the ages of 15 and 24 years. If current trends continue, AIDS can be expected to move into the top five leading causes of death in the pediatric and adolescent age group in the next 3 or 4 years. To address this problem and also to provide focus for the US Department of Health and Human Services activities dealing with pediatric AIDS, an intradepartmental work group was established as a central health and human services component. This was done to ensure the best possible use of federal resources on behalf of children and adolescents with AIDS. Its recommendations are the basis of this report.

Acquired Immunodeficiency Syndrome

Developmental outcome in children exposed to chloride-deficient formula.

The developmental outcome of 2- and 4-year-old children who had been exposed as infants to chloride-deficient formula was studied. A negative dose-response relationship was demonstrated between use of the formula without additional nutritional supplementation and cognitive outcome as measured by the Bayley Scales of Infant Development (Pearson r = -.55, P = .01) at 2 years of age. A similar negative relationship was demonstrated between this exclusive use of the defective formula and perceptual (Pearson r = -.51, P less than .05), motor (Pearson r = -.52, P less than .05), and fine motor (Pearson r = -.75, P less than .002) ability as measured by the McCarthy Scales of Children's Abilities at 4 years of age. When other know predictors of developmental outcome were taken into account by means of multiple linear regression analyses, exclusive formula use emerged as an important predictor of the children's cognitive functioning at 2 years (model R2 = .59, P less than .005) and of quantitative (model R2 = .58, P less than .006), perceptual (model R2 = .63, P less than .009), and fine motor ability (model R2 = .74, P less than .003) at 4 years of age. These data raise concern about the developmental outcome of the children exposed to chloride-deficient formula.

Child, Preschool