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Biomedical subjects

H Pollack

Publications and source records attributed to H Pollack.

At least 19 recordsLinked to original sources

Impaired early growth of infants perinatally infected with human immunodeficiency virus: correlation with viral load.

OBJECTIVE: To evaluate the effect of viral load on the early growth of infants infected with human immunodeficiency virus (HIV). METHODS: Plasma concentrations of p24-antigen and HIV ribonucleic acid were measured retrospectively and correlated with growth parameters for the first 18 months of life in a cohort of 47 term infants born to HIV-infected mothers prospectively enrolled in a study of perinatal HIV transmission. Comparisons of the mean weight and length of the 18 HIV-infected and 29 uninfected infants for each interval and across intervals were made. Viral load was correlated with standard deviation scores. Infants were stratified by high and low viral load during the first 6 months of life. RESULTS: At birth, no difference in weight and length was observed between HIV-infected and uninfected infants. Between birth and 6 months of age, the infected infants grew less rapidly than the uninfected infants, a finding temporally associated with an exponential increase in HIV viremia. The linear growth of infected infants remained consistently less than that of the uninfected infants after 6 months of life, although the differences were no longer statistically significant and tended to decrease with age in parallel with declines in viral load. The median plasma concentration of HIV ribonucleic acid was significantly higher at 3, 6, 12, and 18 months in infected infants in whom growth failure developed. Infants who had a high viral load in the first 6 months of life were significantly more likely to have severe growth failure. Though the mean SD for weight of the infected infants was always less than that of the uninfected infants, the differences were small and not significant. CONCLUSIONS: Our results confirm the observation that stunting is an early frequent finding in perinatal HIV infection. The deleterious effect of HIV on linear growth appears to be correlated with the level of postnatal HIV viremia, although the exact mechanism of this association remains to be elucidated.

Birth Weight

CD8+ T-cell-mediated suppression of HIV replication in the first year of life: association with lower viral load and favorable early survival.

OBJECTIVE AND DESIGN: To study the role and development of non-cytotoxic CD8+ T-cell-mediated suppression of HIV replication in early perinatal HIV infection in a prospective study of vertically infected infants. CD8 T-cell-mediated HIV suppression was measured several times during the first year of life and correlated with viral load, cytotoxic T-cell (CTL) activity, in vitro antibody production (IVAP) and clinical outcome. METHODS: CD8+ T-cell-mediated HIV suppression was measured by comparing the amount of p24 antigen produced by endogenously infected lymphocytes with cultures of the same number of autologous CD4+ T cells from which CD8+ cells were removed immunomagnetically. CD8 viral suppressive activity (VSA) was defined as a > or = 50% reduction in p24 antigen in the cultures containing CD8+ cells. RESULTS: CD8+ T-cell-mediated HIV VSA was detected in 11/16 infants in the first year of life, including six/nine infants studied before 6 months and as early as 3 weeks of age. Infants who demonstrated CD8 VSA had a lower early peak and 6-month 'setpoint' plasma HIV RNA concentration than infants who lacked CD8 VSA [1.51 versus 4.94 and 0.094 versus 0.639 x 10(6) copies/ml, respectively, and higher CD4 percentage at 1 year of age. Survival of infants lacking CD8 VSA (four/six were rapid progressors) was shorter than for infants who demonstrated CD8 VSA (none out of 10 were rapid progressors). CD8 VSA was present before CTL and before or at the same time as IVAP in two of two and 11 of 14 infants studied, respectively. CONCLUSIONS: CD8+ T-cell-mediated VSA can be demonstrated in a large proportion of HIV-infected infants early in the course of infection. This non-cytolytic HIV-suppressive immune response appears to play an important protective role in the early control of perinatal HIV infection at a time when other immune responses are either absent or deficient.

CD4-Positive T-Lymphocytes

KGF facilitates repair of radiation-induced DNA damage in alveolar epithelial cells.

Administration of exogenous keratinocyte growth factor (KGF) prevents or attenuates several forms of oxidant-mediated lung injury. Because DNA damage in epithelial cells is a component of radiation pneumotoxicity, we determined whether KGF ameliorated DNA strand breaks in irradiated A549 cells. Cells were exposed to 137Cs gamma rays, and DNA damage was measured by alkaline unwinding and ethidium bromide fluorescence after a 30-min recovery period. Radiation induced a dose-dependent increase in DNA strand breaks. The percentage of double-stranded DNA after exposure to 30 Gy increased from 44.6 +/- 3.5% in untreated control cells to 61.6 +/- 5.0% in cells cultured with 100 ng/ml KGF for 24 h (P < 0.05). No reduction in DNA damage occurred when the cells were cultured with KGF but maintained at 0 degree C during and after irradiation. The sparing effect of KGF on radiation-induced DNA damage was blocked by aphidicolin, an inhibitor of DNA polymerases-alpha, -delta, and -epsilon and by butylphenyl dGTP, which blocks DNA polymerase-alpha strongly and polymerases-delta and -epsilon less effectively. However, dideoxythymidine triphosphate, a specific inhibitor of DNA polymerase-beta, did not abrogate the KGF effect. Thus KGF increases DNA repair capacity in irradiated pulmonary epithelial cells, an effect mediated at least in part by DNA polymerases-alpha, -delta, and -epsilon. Enhancement of DNA repair capability after cell damage may be one mechanism by which KGF is able to ameliorate oxidant-mediated alveolar epithelial injury.

Aphidicolin

Neurodevelopment, growth, and viral load in HIV-infected infants.

The relation of HIV-1 infection to infant growth and neurodevelopment was studied prospectively in a cohort of 65 infants born to women at risk for HIV infection. No differences were observed at birth between infected infants (INF) and uninfected infants (SR) of HIV-infected women, and infants of uninfected women (SN) with similar socioeconomic background and exposure to drugs. However, postnatal linear growth and cognitive-motor development of INF infants were impaired when compared to SR and SN infants. Declines in linear growth were observed within the first 6 months of life, whereas delays in neurodevelopment were first appreciated at 12 months. In INF infants, decreased linear growth was positively correlated with developmental delay. Moreover, growth and development were both correlated with HIV viral load. INF infants with high plasma HIV RNA copies (> 5 x 10(5)/ ml) at 6 months of life were more likely to exhibit severe growth and developmental delay than infants with a lower viral burden. The implications of these findings with respect to the mechanism of action of HIV-related growth and neurodevelopmental impairments are discussed.

Body Height

The amount of early p24 antigenemia and not the time of first detection of virus predicts the clinical outcome of infants vertically infected with human immunodeficiency virus.

Twenty-three children vertically infected with human immunodeficiency virus type 1 (HIV-1) were studied for viremia during the first days of life. Nine had HIV-1 infection within the first week (early); 14 had HIV-1 first detected by day 11-90 (late). The groups had similar incidence and time of onset of symptomatic HIV-1 infection and survival. CD4 T cell percentages, rates of CD4 T cell attrition, quantitative cell-associated viremia, and p24 antigen concentrations were comparable. Children with peak antigen concentrations >100 pg/mL during the first 6 months (5 early, 6 late) fared worse than those with lower p24 levels. Thus, HIV-1-infected infants with detectable virus in the first few days of life do not have a worse prognosis than infants whose virus is detectable only later. Elevated p24 antigenemia during the first 6 months of life correlates strongly with poor clinical outcome and is independent of the time virus was first detected.

Age Factors

Shortened survival in infants vertically infected with human immunodeficiency virus with elevated p24 antigenemia.

OBJECTIVE: To determine whether the amount of p24 antigenemia in the first 6 months of life is a predictor of survival in children infected vertically with human immunodeficiency virus type 1. METHODS: A retrospective study of vertically infected infants and children who were followed prospectively from early infancy and who had quantitation of plasma p24 antigen concentration in the first 6 months of life. Infants were first stratified by duration of survival as infants who died before 2 years of age (short-term survivors) and infants who survived to 2 years of age (intermediate-term survivors). The median p24 antigen concentration and the proportion of infants in each group with high concentrations of antigen were compared. Analyses with and excluding all p24 determinations made after the use of antiretroviral agents were compared Kaplan-Meier product limit analysis was used to compare survival in infants with low and high antigenemia during the first 6 months of life. RESULTS: The median p24 antigen concentration in 15 short-term survivors was 228 pg/ml, compared with 14 pg/ml in 26 intermediate-term survivors (p < 0.05). The proportion of children with > 100 pg/ml of p24 was higher in short-term than in intermediate-term survivors (p = 0.01). Survival to 2 years of age in infants in whom all p24 antigen values during the first 6 months of life were 100 pg/ml or less was 91%, in comparison with 39% in infants with values greater than 100 pg/ml (p = 0.0017). CONCLUSIONS: Elevated p24 antigenemia in the first 6 months of life is associated with shorter survival and may be a useful predictor of outcome.

Antigens, Viral

Comparison of PCR and standard cytological staining for detection of Pneumocystis carinii from respiratory specimens from patients with or at high risk for infection by human immunodeficiency virus.

The detection of Pneumocystis carinii DNA by PCR was compared with routine cytologic staining techniques (CYT). A total of 284 clinical respiratory specimens, including 137 bronchoalveolar lavage (BAL), 63 bronchoalveolar washing, 63 sputum, and 21 induced sputum samples, obtained from patients with or at high risk for human immunodeficiency virus infection were evaluated. Eighty specimens were positive by PCR, and 69 were positive by CYT. PCR was able to detect P. carinii in more bronchoalveolar washing specimens (15 versus 11) and in comparable BAL specimens (53 versus 54) compared with CYT. PCR was particularly more sensitive than CYT in detecting P. carinii in expectorated sputum (12 versus 4 samples). Of the 19 patients whose respiratory specimens were positive for P. carinii by PCR but negative by CYT, 5 had P. carinii pneumonia (PCP) confirmed by subsequent BAL and transbronchial or mediastinal lymph node biopsy and 9 had a clinical course highly suggestive of acute PCP. Eleven (58%) of the 19 patients with discordant PCR and CYT results had received prior anti-PCP prophylaxis. In this clinical setting in particular and in the evaluation of sputum specimens, the ability of PCR to detect a low parasitic load suggests that this technique may become an important additional tool, along with current cytological methods, for the detection of P. carinii.

Adult

The normal prostate and periprostatic structures: correlation between MR images made with an endorectal coil and cadaveric microtome sections.

This pictorial essay illustrates the normal prostate and periprostatic structures seen on MR images obtained with an endorectal coil and correlates them with anatomic structures identified on serial microtome sections of a frozen human cadaver. The correlation shows that high-resolution MR imaging allows detailed visualization of normal anatomic structures. The ability to identify the normal anatomy and to recognize pathologic alterations provides valuable information concerning clinical decision making for both benign and malignant prostatic disease.

Aged

Correlation of perinatal transmission of human immunodeficiency virus type 1 with maternal viremia and lymphocyte phenotypes.

OBJECTIVE: To determine whether maternal transmission of human immunodeficiency virus (HIV) is correlated with increased quantities of HIV, decreased frequencies of CD4+ T cells, or increased levels of CD8+ T cells in the transmitting mother. METHODS: Peripheral blood obtained from HIV-infected women at different times during pregnancy was used to measure quantitative cell-associated HIV-1 and CD3+CD4+ and CD3+CD8+ proportions; the plasma was used to perform measurements of quantitative viremia by culture and subsequently to measure quantitative HIV-1 ribonucleic acid levels. These measurements were analyzed with respect to their association with HIV transmission to the baby, which occurred in one fourth of the cases. The children were also studied to determine whether HIV-1 was detected near birth or not until 1 to 8 weeks of life. RESULTS: Increased clonal frequencies of HIV-1-infected peripheral blood mononuclear cells were found in mothers of infected children; fivefold fewer cells were required for a positive culture result (median cell numbers of 10(4.5) vs 10(5.2); p = 0.008). Higher frequencies of infected cells were seen in mothers of babies with evidence of infection at birth than in mothers of infected babies without evidence of infection at birth (p < 0.05). Plasma viremia was measured in 10% of cultures without regard to whether the mothers transmitted virus to their babies. Increased levels of ribonucleic acid as detected by the branched-chain DNA method were measurable more often (45% vs 17%) in the mothers of infected children than in mothers of uninfected children. Proportions of CD4+ and CD8+ T cells were indistinguishable in these two groups of women. CONCLUSIONS: Increased viremia was present in mothers who transmitted HIV to their offspring. This variable could be used to select women at highest risk of transmitting HIV to their offspring for treatment to decrease the HIV burden five-fold.

CD4-CD8 Ratio

Efficacy of primary chemoprophylaxis against Pneumocystis carinii pneumonia during the first year of life in infants infected with human immunodeficiency virus type 1.

To evaluate the efficacy of primary chemoprophylaxis in preventing Pneumocystis carinii pneumonia (PCP) in infants with perinatal human immunodeficiency virus-1 infection during the first year of life, we conducted a retrospective chart review of infants with human immunodeficiency virus-1 infection born at New York University Medical Center-Bellevue Hospital Center, in New York. Between March 1989 and March 1993, 24 infants received primary chemoprophylaxis with trimethoprim-sulfamethoxazole in the first year of life and 24 infants did not receive primary prophylaxis. The CD4+ T-lymphocyte counts in the two groups did not differ during the first year of life. The median age at the time of initiation of prophylaxis was 3 months, and the average duration of prophylaxis was 5.5 months. Among the infants who had not received prophylaxis, five cases of PCP were diagnosed at a median age of 5 months; in contrast, no cases of PCP were observed in the infants receiving prophylaxis (log-rank test, p = 0.017). The probability of surviving after 1 year of age was 92% for the children who received prophylaxis and 74% for those who did not (log-rank test, p = 0.035). These data indicate that chemoprophylaxis is highly effective in preventing primary PCP and improving survival time in infants with human immunodeficiency virus-1 infection.

AIDS-Related Opportunistic Infections

Effects of antiviral therapy on the production of anti-human immunodeficiency virus-specific immunoglobulin in infants and children.

The effect of zidovudine therapy on human immunodeficiency virus (HIV)-specific antibody production was studied in 64 HIV-1-infected infants and children > 6 months old. HIV-specific in vitro antibody production (IVAP) was measured in cultures of peripheral blood mononuclear cells (PBMC). IVAP decreased in 85% of children after zidovudine was initiated (mean decline, 1 log within 2 months). Effects were seen as early as 1 week after starting zidovudine. No change in IVAP was seen in children not treated. In comparison, plasma core (p24) antigen levels declined and CD4+ lymphocytes increased in only 42% and 52%, respectively, of treated subjects. Thus, the production of antibody to HIV-1 decreases rapidly after the initiation of antiretroviral therapy. This response to therapy may provide a simple and sensitive method of monitoring antiretroviral therapy.

Acquired Immunodeficiency Syndrome

Streptococcus pneumoniae in human immunodeficiency virus type 1-infected children.

The purpose of this study was to characterize systemic Streptococcus pneumoniae disease in human immunodeficiency virus type 1 (HIV-1)-infected children. All cases of bacteremia and meningitis caused by S. pneumoniae among children less than 18 years old were collected by review of the Microbiology Laboratory records at the Bellevue Hospital Center during the period August 1, 1978, through July 31, 1993. There were 31 bouts of systemic S. pneumoniae disease in 19 of 235 HIV-1-infected children cared for by the Pediatric Infectious Disease staff and 116 bouts in 113 children not known to be HIV-1-infected. Four of the 19 HIV-1-infected children had multiple episodes of S. pneumoniae bacteremia as compared with 3 of 113 in the general population (P = 0.008). The frequency of serotypes and distribution of infections by season of the year did not differ between the 2 groups. The median ages at the time of the S. pneumoniae infection were 1.8 and 1.1 years for the HIV-1-infected children and the general population of children, respectively, when those children with multiple episodes were included for their initial episode only (P = 0.06). In the HIV-1-infected patients, 10 episodes were associated with pneumonia, 5 with pneumonia and otitis media, 5 with otitis media only, 1 with pneumonia and meningitis, 1 with meningitis only and 1 with periorbital cellulitis; 5 had no apparent focus of infection. One episode of pneumonia was complicated by lung abscess and there were 2 deaths. Most HIV-1-infected patients recovered without significant sequelae, and the clinical course of their systemic infections did not appear to be markedly different than that of healthy children.

AIDS-Related Opportunistic Infections

Imaging in the diagnosis and assessment of prognosis in localized prostate cancer. Consensus Conference on Diagnosis and Prognostic Parameters in Localized Prostate Cancer. Stockholm, Sweden, May 12-13, 1993.

As part of a WHO consensus conference on diagnosis and prognostic parameters in localized prostate cancer, a working group of experts discussed the role of various modern imaging techniques. Special attention was focused on transrectal ultrasound (TRUS) in combination with biopsies, magnetic resonance imaging (MRI) using endorectal coil and recent advances in these techniques. Some experimental techniques, especially hormone receptor scintigraphy and positron emission tomography were also discussed and new results were presented. We concluded that MRI seems to be superior to other imaging techniques in the preoperative assessment of local tumor stage. TRUS defends its place in the diagnostic armament; it is easily combined with multiple biopsies, the results of which are important in the assessment of the biological aggressiveness of prostate cancer. The present development in the field of nuclear medicine may result in techniques for in vivo characterization of tumors and will most certainly have important implications for diagnosis of prostate cancer in the future.

Animals

Ontogeny of anti-human immunodeficiency virus (HIV) antibody production in HIV-1-infected infants.

The early serologic response of infants to infection with human immunodeficiency virus type 1 (HIV-1) is normally obscured by the presence of transplacentally acquired maternal HIV antibody. By measuring HIV antibody produced in vitro by lymphocytes isolated from peripheral blood of infants and children of HIV-1-infected mothers, we have been able to study the natural acquisition of humoral immunity to perinatal HIV-1 infection. One hundred ninety-seven infants of HIV-1-infected women were studied prospectively and longitudinally from birth. In the neonatal period, infected infants produced only small amounts of HIV-specific IgG antibodies to a restricted number of antigens. The amount of immunoglobulin to HIV-1 and the number of HIV-1 antigens recognized increased with age. After 6 months of life 85% of infected infants made detectable antibody to two or more viral proteins. Antibody to gp160 appeared first and was the most frequently found at all ages, followed by antibody to the envelope proteins gp120 and gp41. The amount of HIV antibody produced correlated positively with the percentage of CD4+ T lymphocytes in peripheral blood. This assay provides a method of studying the immunogenicity of vaccines against HIV-1 in HIV-1-infected infants and of assessing the effect of early therapeutic interventions on the humoral response to HIV-1.

Acquired Immunodeficiency Syndrome

A novel detection assay for the early diagnosis of HIV-1 infected infants.

This investigation compares the results of a new method of diagnosing HIV-1 infection in infants < 6 months of age with currently employed techniques including cocultivation, the polymerase chain reaction (PCR), serum p24 antigen, and in vitro antibody production (IVAP) measurements. The new method, called in vitro antigen (IVAG), measures p24 antigen released into culture supernatants of peripheral blood mononuclear cells that are incubated with Epstein-Barr virus (EBV). No activated donor lymphocytes or interleukin 2 (IL-2) are added to the culture. Using this technique, HIV-1 infection was detected in 15 of 17 HIV-1-infected infants < 2 months of age, including 3 of 7 infants tested at birth, and 15 of 15 HIV-1-infected infants between 2 and 6 months of age. None of 83 determinations of 15 uninfected infants were positive. These results were found to be comparable to results obtained by the traditional cocultivation technique and the polymerase chain reaction. Because of its simplicity and reduced cost, this sensitive and specific assay could be a valuable addition to the current methods of diagnosis of HIV-1 infection in young infants.

Cells, Cultured