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Biomedical subjects

Y J Bryson

Publications and source records attributed to Y J Bryson.

At least 37 records · Page 2Linked to original sources
PubMed1996

Perinatal HIV-1 transmission: recent advances and therapeutic interventions.

OBJECTIVES: To review recent advances and current understanding of risk factors associated with perinatal HIV-1 transmission, the critical gaps in our knowledge, and current and future approaches to prevention of transmission. FACTORS INFLUENCING MOTHER-TO-CHILD TRANSMISSION: Perinatal HIV transmission is multifactorial and all potential risk factors must be considered in the context of the timing of transmission in utero, at birth or after birth by breastfeeding. Major factors that have been associated with increased transmission include a high maternal virus load, decreased CD4+ count, lack of HIV neutralizing antibody, advanced clinical disease, primary infection, first-born twins, and obstetric factors including chorioamnionitis, mode of delivery and more than 4 h of ruptured membranes. There are still significant gaps in our knowledge to explain the known variables in transmission, including the fact that 70-80% of infants born of HIV-infected mothers escape infection. APPROACHES TO REDUCE PERINATAL HIV-1 INFECTION: One of the major advances in prevention of perinatal transmission was the AIDS Clinical Trials Group 076 trial, which showed that antiretroviral therapy with zidovudine given to the mother during pregnancy and delivery, and to the infant, reduced transmission by 70%. Current approaches to further reduce transmission and provide practical application worldwide are discussed, including combined potent antivirals, local approaches and immune-based therapy given to the mother and/or infant. CONCLUSIONS: There is reason for optimism for the potential to further reduce perinatal transmission to a level of less than 2%. The challenge will be to increase education and awareness worldwide in order to translate scientific advances into practical approaches that will be applicable in both industrialized and non-industrialized countries.

Clinical Trials as Topic↗
PubMed1995

Clearance of HIV infection in a perinatally infected infant.

BACKGROUND: We describe a child who was identified shortly after birth as infected with the human immunodeficiency virus type 1 (HIV-1), but whose infection appears to have completely cleared. Asymptomatic HIV-1 infection was diagnosed in the mother during the fourth month of pregnancy. The infant was delivered vaginally at 36 weeks, received no blood products, and was not breast-fed. METHODS AND RESULTS: HIV-1 was detected by culture of the infant's peripheral-blood mononuclear cells at 19 and 51 days of age. Plasma from the infant was also culture-positive for HIV-1 at 51 days of age by DNA polymerase chain reaction (PCR). Nucleotide-sequence analysis of HIV-1 DNA showed extremely close homology of the cultures obtained 32 days apart, and forensic markers of genetic identity for the two cultures were identical. Hence, inadvertent viral contamination or error in the collection of specimens was highly unlikely. At 12 months of age the infant was seronegative for HIV-1, and numerous subsequent cultures and tests by PCR have also been negative for HIV-1. The child is five years of age at this writing, is HIV-seronegative, and remains well, with normal growth and development and no laboratory or clinical evidence of HIV-1 infection. CONCLUSIONS: The infant we describe was infected perinatally with HIV-1, but the infection subsequently cleared and the infant remained without detectable HIV-1 infection five years later.

Adult↗
PubMed1995

Correlation of clinical progression in human immunodeficiency virus-infected children with in vitro zidovudine resistance measured by a direct quantitative peripheral blood lymphocyte assay.

A rapid method for determination of zidovudine resistance was developed and results were correlated with clinical outcome in human immunodeficiency virus (HIV)-infected children. The zidovudine susceptibilities of HIV-1 isolates from 34 children were determined through a direct quantitative peripheral blood lymphocyte assay and compared with results of the AIDS Clinical Trials Group resistance assay. Patients' peripheral blood lymphocytes were 5-fold diluted and cocultured with donor lymphocytes and varying concentrations of zidovudine. Isolates were defined as sensitive if inhibited by < or = 1.0 microM zidovudine and resistant at > 1.0 microM. Children (n = 21) with zidovudine-resistant virus had greater evidence of disease progression than did those with zidovudine-sensitive virus (n = 11) as demonstrated by failure to thrive (57% vs. 9%, P = .01) and opportunistic infections (48% vs. 0, P = .006). This assay may be useful as a screening tool for development of clinically relevant zidovudine resistance.

Child↗
PubMed1994

A controlled trial of intravenous immune globulin for the prevention of serious bacterial infections in children receiving zidovudine for advanced human immunodeficiency virus infection. Pediatric AIDS Clinical Trials Group.

BACKGROUND: Serious bacterial infections are common in children infected with the human immunodeficiency virus (HIV). Studies performed before zidovudine became standard therapy found that intravenous immune globulin decreases the number of serious bacterial infections in these children. We designed a multicenter study to evaluate the efficacy of intravenous immune globulin in children with advanced HIV infection who were receiving zidovudine. METHODS: In a double-blind trial 255 children between 3 months and 12 years of age who had the acquired immunodeficiency syndrome (AIDS) or AIDS-related complex were randomly assigned to receive either intravenous immune globulin (400 mg per kilogram of body weight) (n = 129) or placebo (0.1 percent albumin) (n = 126) every 28 days. All children received 180 mg of zidovudine per square meter of body-surface area orally four times daily. Treatment assignment was stratified according to whether the patients had a history of one or more serious bacterial infections, had previously been treated with zidovudine, or were currently receiving prophylaxis with trimethoprim-sulfamethoxazole. The median length of follow-up was 30.6 months. RESULTS: The estimated two-year rates of serious bacterial infections with confirmed pathogens were 16.9 percent for the immune globulin group and 24.3 percent for the placebo group (relative risk, 0.60; 95 percent confidence interval, 0.35 to 1.04; P = 0.07). The treatment effect was seen primarily among the 174 children who were not receiving trimethoprim-sulfamethoxazole prophylaxis at entry; the estimated two-year rates of infection were 11.3 percent for the immune globulin group and 26.8 percent for the placebo group (relative risk, 0.45; 95 percent confidence interval, 0.22 to 0.91; P = 0.03). For the 81 children who were receiving trimethoprim-sulfamethoxazole prophylaxis initially, the rates were 27.7 percent in the immune globulin group and 17.7 percent in the placebo group (relative risk, 1.26; 95 percent confidence interval, 0.44 to 3.66; P = 0.67). The two-year survival was similar in the two groups: 79.2 percent among immune globulin recipients and 75.4 percent among placebo recipients (P = 0.41). CONCLUSIONS: In children with advanced HIV disease who are receiving zidovudine, intravenous immune globulin decreases the risk of serious bacterial infections. However, this benefit is apparent only in children who are not receiving trimethoprim-sulfamethoxazole as prophylaxis.

AIDS-Related Complex↗
PubMed1994

T cell activation in pediatric AIDS pathogenesis: three-color immunophenotyping.

Immune activation is an important component of HIV disease in adults that may reflect a protective host response and/or be a component of immunopathogenesis. The goals of this study were to gain understanding of T cell activation in pediatric HIV disease, to assess the usefulness of T cell activation markers as surrogates for disease progression and/or early identification of infection in infants at risk, and to determine any advantages of three- compared to two-color flow cytometric immunophenotyping for the above assessments. We examined the expression of cell-surface activation antigens on the CD4 and CD8 T cells of 26 HIV-infected and 40 HIV-seronegative age-matched control children. Compared with controls, HIV-infected children showed a slight but not significant decrease in the proportion of CD4 cells that coexpressed CD45RA and L-selectin (mean of 83 vs 75% for < 2 years of age, 76 vs 62% for 2-3 years, 64 vs 56% for > or = 4 years). CD4 cells coexpressing CD38 and HLA-DR were significantly increased in HIV+ children (mean of 2 vs 6% for < 2 years of age, 3 vs 11% for 2-3 years, 2 vs 8% for > or = 4 years). There was a striking and significant increase in the proportion of CD8 cells coexpressing CD38 and HLA-DR (mean of 5 vs. 25% for < 2 years, 10 vs 41% for 2-3 years, 6 vs 31% for > or = 4 years); this double positive population of CD8 cells included cells that were approximately 1 log brighter for the expression of CD38 than for that of CD38 single-positive cells. There was a significant reduction in CD45RA+ CD8 cells (means of 92 vs 71% for < 2 years of age, 88 vs 50% for 2-3 years, 80 vs 57% for > or = 4 years) and an increase in CD57+ CD8 cells (mean of 4 vs 8% for < 2 years of age, 8 vs 22% for 2-3 years, 19 vs 31% for > or = 4 years) in HIV+ children. The inclusion of CD3 as an anchor marker for CD8 cell subsets to limit the analysis to CD3+ CD8 cells did not substantially alter the data nor enhance the differences between infected and control children compared with the analysis of all CD8 cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Acquired Immunodeficiency Syndrome↗
PubMed1993

Clinical reactivation of herpes simplex virus type 2 infection in seropositive pregnant women with no history of genital herpes.

OBJECTIVE: To determine the risk for genital herpes and asymptomatic herpes simplex virus (HSV) shedding in late pregnancy and delivery in a population of HSV type 2 (HSV-2)-seropositive but previously asymptomatic pregnant women. DESIGN: A prospective inception cohort study. PARTICIPANTS: A total of 1355 pregnant women with no history of genital herpes referred from three private obstetrics practices between November 1985 and June 1988. MAIN OUTCOME MEASURES: Confidential questionnaires evaluated sexual risk factors in relation to HSV-2 serologic status as determined by Western blot analysis. Herpes simplex virus shedding was determined by viral culture of the cervix and vulva and of any suspicious lesions. RESULTS: Antibody to HSV-2 was detected in 439 of 1355 pregnant women (32%) with no history of genital herpes. Asymptomatic HSV shedding was detected in 5 of 1160 cultures (0.43%) obtained in late pregnancy and during delivery. A first episode of clinical genital herpes was recognized by 43 of 264 HSV-2-seropositive women (16%) during their pregnancy. CONCLUSIONS: Serologic evidence of unknown HSV-2 infection was common in pregnant women without a history of genital herpes. Asymptomatic viral shedding in these women occurred at a rate similar to that seen in women with symptomatic genital HSV-2 infection. To improve recognition of genital herpes near term, obstetricians should counsel pregnant women about the high prevalence and mild and diverse symptoms of genital HSV-2 infection.

Adult↗
PubMed1993

Effect of oral acyclovir on pain resolution in herpes zoster: a reanalysis.

The most frequent complication of herpes zoster is postherpetic neuralgia, usually defined as chronic pain in the area of the exanthem that persists for at least a month after the skin lesions have healed. Several clinical studies of acyclovir showed a reduction in severity and duration of acute pain, but provided no definitive data for chronic pain. In order to determine if acyclovir therapy could reduce chronic pain, we reanalyzed data from the largest U.S. placebo-controlled treatment trial of 187 immunocompetent persons with herpes zoster. By considering pain as a continuum, we found that the median duration of pain in acyclovir recipients was 20 days vs. 62 days for their placebo counterparts (P = 0.02). Thus, acyclovir has been shown to reduce chronic zoster-associated pain. We also noted that the absence of pain at the onset of cutaneous herpes zoster did not preclude its later development.

Acyclovir↗
PubMed1993

The pharmacokinetics and safety of zidovudine in the third trimester of pregnancy for women infected with human immunodeficiency virus and their infants: phase I acquired immunodeficiency syndrome clinical trials group study (protocol 082). Zidovudine Collaborative Working Group.

OBJECTIVES: We measured the pharmacokinetics and safety of zidovudine in pregnant women infected with human immunodeficiency virus and their offspring. STUDY DESIGN: Asymptomatic human immunodeficiency virus-infected women with uncomplicated singleton gestations (28 to 36 weeks) underwent parenteral and oral zidovudine treatment during pregnancy and labor. Maternal and neonatal drug levels were measured at delivery and sequentially for 48 hours. Infants were followed up for 18 months. RESULTS: The total body clearance (26.3 +/- 10.1 ml/min/kg), mean terminal elimination phase zidovudine half-life (1.3 +/- 0.2 hours), and urinary zidovudine recovery were similar to values in nonpregnant adults. Essentially equivalent zidovudine levels in the mother and neonate at delivery implied little, if any, fetal zidovudine metabolism. The half-life of zidovudine in the neonates was tenfold that of the mother. No significant adverse effects were noted in the infant at birth or on follow-up. CONCLUSIONS: In both mothers and infants the drug appeared safe and well tolerated with no significant hematologic abnormalities.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Increased susceptibility of neonatal monocyte/macrophages to HIV-1 infection.

The relative susceptibility of neonatal/cord blood monocyte/macrophages to productive infection with human immunodeficiency virus type 1 (HIV-1) was investigated. In addition, the effect of HIV-1 infection of cord blood monocyte/macrophages in various stages of maturation/differentiation as represented by differing ages of monocytes in culture was examined. Monocyte/macrophages were infected with two viral strains isolated and cloned from primary clinical isolates, each with different cell tropisms. Cord blood and adult monocyte/macrophages were infected with either the macrophage-tropic strain HIV-1(JR-FL) or the predominantly lymphocyte-tropic strain HIV-1(JR-CSF). p24gag antigen levels were measured in supernatants by ELISA. Cord monocyte/macrophages at three different ages in culture (4, 7, and 11 days) were more productively infected by both viral strains than were adult monocyte/macrophages infected in parallel. In addition, the less differentiated cells (cord and adult monocyte/macrophages infected after growing 4 days in culture) were more productively infected than were the more differentiated monocyte/macrophages (cells infected after growing 7 or 11 days in culture). The mechanism for this increased susceptibility of cord monocyte/macrophages to HIV-1 infection as compared to adult cells was also investigated. A measurable increase in DNA synthesis was found in the infected cord cells when compared to infected adult cells and to uninfected adult or cord cells as represented by increased [3H]thymidine incorporation, suggesting that increased cell proliferation of cord monocyte/macrophages may enhance the permissivity of infection. This article suggests that cord monocyte/macrophages may play an important role in the pathogenesis of perinatal HIV-1 infection.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

In vitro insulin-like growth factor-I, growth hormone, and insulin resistance occurs in symptomatic human immunodeficiency virus-1-infected children.

Poor growth is a common feature of symptomatic children (Centers for Disease Control stage P2) infected with human immunodeficiency virus-1 (HIV-1). However, several previous studies have failed to show any relationship between serum hormone levels and poor growth. To assess the roles of hormone deficiency and hormone resistance in the development of poor growth in HIV-1-infected children, we studied six asymptomatic Centers for Disease Control stage P1 [height SD score = 0.01 +/- 1.0 (mean +/- SD)], 10 P2 (height SD score = -2.0 +/- 1.0), and six short, normal children (height SD score = -2.4 +/- 1.2). Mean weight:height SD scores were similar in all three groups, suggesting that gross nutritional status did not differ between groups. There were no significant differences between groups with respect to mean plasma levels of IGF-I, thyroid hormones, TSH, and cortisol. As an index of hormone sensitivity, we quantified in vitro colony formation of erythroid progenitor cells, isolated from peripheral blood of study subjects, in response to IGF-I, growth hormone (GH), and insulin. P2 subjects had a quantitative mean reduction in erythroid progenitor cells colony formation in response to IGF-I of 32% compared with P1 subjects (p = 0.001 by analysis of variance) and 21% compared with controls (p = 0.006); in response to GH of 21% compared with controls (p = 0.015); and in response to insulin of 35% compared with P1 subjects (p = 0.038) and 34% compared with controls (p = 0.004).(ABSTRACT TRUNCATED AT 250 WORDS)

Child↗
PubMed1992

The management of pregnancies complicated by genital infections with herpes simplex virus.

In this review we summarize current knowledge related to the identification of pregnancies that may be complicated by genital herpes and describe the consequences of maternal infections with genital herpes. We address the implications of this information for the management of genital herpes during pregnancy and at delivery and for the care of neonates exposed to herpes simplex virus at delivery. On the basis of the current data, we cannot make specific recommendations concerning many of the clinical problems that are caused by herpes simplex virus infections in pregnant women. We identify and discuss unresolved questions about optimal management.

Female↗
PubMed1991

Induction of interferon-gamma by cord blood mononuclear cells is calcium dependent.

Human cord blood mononuclear cells (MNCs) are deficient in their ability to produce interferon-gamma (IFN-gamma). Previous studies have shown that phytohemagglutinin (PHA)-stimulated neonatal MNCs produced significantly less IFN-gamma than adult PHA-stimulated MNCs. The deficient IFN-gamma production is partly due to the absence of a macrophage-derived soluble mediator. Supernatants from PHA-stimulated adult macrophages and phorbol myristate acetate (PMA)-stimulated U937 cells (which were dialyzed prior to culture to remove PMA) increased IFN-gamma production in neonatal PHA-stimulated MNC (14 to 217 units/ml and 14 to 293 units/ml, respectively). The requirement for a soluble macrophage mediator was replaced by the addition of exogenous calcium chloride (CaCl2) to PHA-stimulated cord blood MNCs. The increase in IFN-gamma production by exogenous CaCl2 was blocked by the addition of the calcium channel blocker, manganese chloride (MnCl2). Furthermore, the increased IFN-gamma production by PHA-stimulated cord blood MNC in the presence of PHA-stimulated adult macrophage supernatant or PMA-stimulated U937 supernatant was abrogated by the addition of MnCl2, chlorpromazine, and verapamil. These data suggested that the soluble factor produced by PHA-stimulated adult macrophage supernatant and PHA-stimulated U937 supernatant induced IFN-gamma production in PHA-stimulated cord blood MNC by inducing calcium-dependent signals at more than one site.

Calcium↗
PubMed1991

Pharmacokinetics of acyclovir in the term human pregnancy and neonate.

Concern about neonatal herpes often leads to cesarean delivery of infants in women with a history of genital herpes. The antiviral drug acyclovir has been used effectively to suppress genital herpes simplex virus recurrences in nonpregnant adults. Its administration to pregnant women with recurrent genital herpes may reduce herpes simplex virus recurrences and thus may decrease the cesarean section rate among this population. To study the pharmacokinetics, safety, and patient tolerance of suppressive oral acyclovir, either 200 mg (n = 7) or 400 mg (n = 8) was administered orally every 8 hours to pregnant women with a history of recurrent herpes simplex virus, from 38 weeks' gestation until delivery. The mean +/- SD plasma levels for the 200 and 400 mg groups, respectively, were: first dose peak, 1.7 +/- 0.6 and 2.3 +/- 1.0 mumol/L; steady-state trough, 0.7 +/- 0.3 and 0.8 +/- 0.6 mumol/L; steady-state peak, 1.9 +/- 1.0 and 3.3 +/- 1.0 mumol/L. In late gestation maternal acyclovir pharmacokinetics were similar to those of nonpregnant adults from other studies. Acyclovir was concentrated in the amniotic fluid; however, there was no accumulation in the fetus (mean maternal/infant plasma ratio at delivery was 1.3). Acyclovir was well tolerated, and no toxicity was seen in the mothers or infants. The administration of acyclovir, 400 mg every 8 hours, appears appropriate for use in an efficacy and safety study regarding suppression of herpes simplex virus recurrences during the last weeks of pregnancy.

Acyclovir↗
PubMed1991

Uptake of extracellular Ca2+ is a requirement for production of interferon-gamma by cord blood mononuclear cells.

We studied the response of adult peripheral and cord blood mononuclear cells (MNCs) to graded concentrations of phytohemagglutinin (PHA) to characterize the requirements for proliferation and interferon-gamma (IFN-gamma) production. As the concentration of PHA was decreased, the proliferative response of both adult and cord blood MNCs decreased in parallel. At high concentrations of PHA (a: 120) cord blood MNCs display normal high proliferation but IFN-gamma production was greatly diminished compared with adult MNCs. Addition of the calcium ionophore, A23187, to PHA-stimulated adult MNCs had no effect on proliferation or IFN-gamma production at any of the concentrations of PHA tested. Furthermore, A23187 alone had no effect on proliferation or IFN-gamma secretion. Similarly, the addition of A23187 to PHA-stimulated cord-blood MNCs had no effect on proliferation. However, when A23187 was added to high dose (1:120) PHA-stimulated cord blood MNCs IFN-gamma production increased to levels comparable with adult PHA-stimulated MNCs. A similar pattern of response was seen when exogenous calcium chloride was added in place of A23187.

Calcimycin↗