PubMed Health⌕ Search

Biomedical subjects

A Deveikis

Publications and source records attributed to A Deveikis.

16 recordsLinked to original sources

Cerebral metabolites in HIV-infected children followed for 10 months with 1H-MRS.

BACKGROUND: Previous studies have shown that HIV-infected children have abnormal cerebral metabolites, measured by proton MR spectroscopy (1H MRS), but the stability of these measurements over time has not been described in HIV-infected children. The authors recently reported a study of cerebral metabolites in 20 HIV-infected children (6 to 16 years of age); the current study followed 12 of these children (10.0 years +/- 3.7 years) and repeated the MR spectroscopy at 24.1 +/- 3.7 weeks and 42.2 +/- 3.5 weeks following the entry time with repeated neuropsychological testing. METHODS: 1H MR spectra were acquired at 1.5 T (GE Signa, PRESS localization, repetition time = 3,000 msec, echo time = 30 msec). Five brain regions were studied: right frontal white matter, left frontal white matter, right basal ganglia, right hippocampus, and midfrontal gray matter. The concentrations of N-acetylaspartate (NAA), choline (CHO), creatine (CR), and myo-inositol (mI) and the ratio of each metabolite to CR were determined. RESULTS: There were no changes in the metabolite concentrations or metabolite/CR ratios at the three time periods. Similarly, during this follow-up period, HIV-positive children showed no changes in clinical signs, HIV viral loads, CD4%, or CD4 counts, except for improved spatial memory with repeat testing. CONCLUSION: In a clinically and neurologically stable group of HIV-infected children, cerebral metabolites were stable over a 10-month time period, suggesting that it is possible to assess changes in cerebral metabolites as a measure of cerebral health, but longer follow-up in a larger sample is needed.

Adolescent↗

Altered neurometabolite development in HIV-infected children: correlation with neuropsychological tests.

BACKGROUND: HIV-infected children have abnormal cerebral metabolites, measured by proton MR spectroscopy ((1)H-MRS), but how these abnormalities relate to brain function is unclear. METHODS: Metabolite concentrations in five brain regions of 20 HIV-infected and 13 control children were measured, and these findings were correlated with age, log(10) plasma viral load, CD4 count, and neuropsychological scores. RESULTS: Compared with control subjects, HIV patients had decreased choline concentration [Cho] in left frontal white matter (LFW) (-12%; p = 0.04); those with high viral load (>5,000 HIV RNA copies/mL) had decreased right basal ganglia (RBG) [Cho] (-15%; p = 0.005), and [Cr] (-13%; p = 0.02). Patients with high viral load also had higher [Cho] in the midfrontal gray matter (MFG) (+25%; p = 0.002) and lower myo-inositol [Ins] in the RBG (-18%; p = 0.04) than patients with low HIV viral load. N-Acetyl aspartate concentration ([NAA]) correlated with age in right frontal white matter (RFW) (r = 0.59, p = 0.04), LFW (r = 0.66, p = 0.02), and right hippocampus (RHIP) (r = 0.69, p = 0.02) only in control subjects. In contrast, [Ins] correlated with age in both RFW and LFW (r = 0.71, p = 0.0006; r = 0.65, p = 0.006) only in the HIV patients. Log(10) plasma viral load correlated positively with [Ins] in RFW (r = 0.54, p = 0.02) and [Cho] in MFG (r = 0.49, p = 0.04). Compared with control subjects, HIV patients had poorer spatial memory (p = 0.045) and delayed spatial memory correlated with [Cho] in RHIP (r = 0.68, p = 0.02). CONCLUSIONS: These data suggest that normal brain development may be affected in children infected with HIV at birth, particularly evidenced by the lack of age-related increases in the neuronal marker [NAA]. Early, aggressive treatment of infants with HIV before development of encephalopathy is warranted.

Adolescent↗

Effect of protease inhibitors combined with standard antiretroviral therapy on linear growth and weight gain in human immunodeficiency virus type 1-infected children.

Children with HIV-1 infection and poor growth have a significant increase in the risk of death. We studied the effects of protease inhibitors on the height and weight of 27 HIV-1-infected children and found that in our small pilot study, protease inhibitor therapy had a positive effect on the heights of HIV-1-infected children. Accelerated height velocity was sustained for at least 18 to 20 months.

Adolescent↗

Pneumococcal and influenza immunization and human immunodeficiency virus load in children.

OBJECTIVE: HIV-infected children receiving influenza vaccine, pneumococcal vaccine and both vaccines concurrently were studied to examine the effect of immunization on plasma HIV viral load. METHODS: Thirteen children received immunizations: pneumococcal vaccine, 5; pneumococcal and influenza vaccines, 7; and influenza vaccine, 1. Most patients (12 of 13) were receiving combination reverse transcriptase inhibitor antiretroviral therapy without protease inhibitors at the time of immunization. Baseline plasma HIV RNA was determined 1 month prior (11 of 13), 2 weeks prior (12 of 13) and on the day of immunization (12 of 13). Plasma HIV RNA was assayed at 2 weeks (11 of 13), 4 weeks (12 of 13) and 3 months (5 of 13) after immunization. T cell activation markers (HLA-DR+, CD38+ and CD45RO+, CD28+) were examined for both CD4+ and CD8+ lymphocytes on the day of immunization and 2 weeks after immunization for 11 children. RESULTS: Only one child developed a >0.5-log increase in viral load at any time after immunization. There was no correlation between an increase in viral load and antibody response to pneumococcal vaccine. At least one activation marker increased (> 10%) for two children receiving pneumococcal vaccine and two children receiving pneumococcal and influenza vaccines. One of these children experienced an increase in viral load. CONCLUSION: Immunization with pneumococcal and influenza vaccines, alone or in combination, is rarely associated with a significant increase in HIV plasma RNA in children receiving combination antiretroviral therapy.

Anti-HIV Agents↗

A "bloodless cesarean section" and perinatal transmission of the human immunodeficiency virus.

OBJECTIVE: Perinatal transmission of the human immunodeficiency virus is the main pathway for children to become infected with this virus; however, the relative contribution and timing of this transmission, whether transplacental or by exposure through the birth process, have not yet been elucidated. An obvious question is whether the mode of delivery has an impact on this transmission rate. However, a routine cesarean section will primarily diminish the duration of exposure of maternal bodily fluids to the neonate but does not prevent the baby from being exposed to maternal blood coming from the uterine incision. The purpose of this study was to determine whether the rate of perinatal transmission of human immunodeficiency virus could be significantly lowered by delivering the baby with minimal to no exposure to maternal blood or bodily fluids by the use of a surgical technique termed a "bloodless cesarean section." STUDY DESIGN: We performed a prospective cohort study in a group of pregnant women infected with human immunodeficiency virus and evaluated the rate of transmission of this virus to the neonate on the basis of the mode of delivery. One group of patients was delivered by means of a "bloodless cesarean section," in which the baby was delivered and not exposed to any maternal blood or bodily fluid. The control group gave birth either by vaginal delivery or by routine cesarean section. All of the newborns were followed up for a minimum of 15 months or until negative findings were confirmed. Multiple antenatal, intrapartum, and postdelivery variables were collected and analyzed. RESULTS: A total of 108 patients were included in this study and 14 neonates became infected with human immunodeficiency virus (13%). Three of 53 infants delivered by a bloodless cesarean section (5.7%) became infected compared with 11 of 55 control patients (20.0%). This was significant at P = .02 and represented an absolute difference in percentage between the 2 groups of 14.3%, which corresponds to a 71.5% relative reduction in transmission risk (z = 2.27, P = .012). Since the use of zidovudine greatly influences the perinatal transmission rate of human immunodeficiency virus, the study data were reanalyzed with the exclusion of patients who used antenatal or intrapartum zidovudine. Two of 32 infants in the bloodless cesarean section group (6.3%) were infected compared with 9 of 38 in the control group (23.7%). This was significant at P = .04 and revealed an absolute difference in percentage of 17.4%, which corresponds to a 73.4% relative reduction in transmission risk (z = 2.15, P = .016). There was no difference in the transmission rate between the bloodless cesarean section patients who did not use zidovudine (2/32, 6.3%) and the patients who did use zidovudine from the entire study population (3/38, 7.9%). CONCLUSION: In the absence of zidovudine usage, these data show that 70% to 75% of the perinatal transmission of human immunodeficiency virus to a newborn occurs from exposure to maternal blood and bodily fluids at the time of birth. This information is important for patients unable to take zidovudine or other antiretroviral agents, but more important, it introduces the concept of other treatment options for the future.

Adult↗

Early prognostic indicators in primary perinatal human immunodeficiency virus type 1 infection: importance of viral RNA and the timing of transmission on long-term outcome.

The time of perinatal human immunodeficiency virus type 1 (HIV-1) transmission and the pattern of early plasma viremia as predictors of disease progression were evaluated in infected infants followed from birth. Cox proportional hazards modeling demonstrated that a 1-log higher HIV-1 RNA copy number at birth was associated with a 40% increase in the relative hazard (RH) of developing CDC class A or B symptoms (P = .004), a 60% increase in developing AIDS (P = .01), and an 80% increase in the of risk death (P = .023) over the follow-up period of up to 8 years. The peak HIV-1 RNA copy number for infants during primary viremia was also predictive of progression to AIDS (RH, 9.9; 95% confidence interval [95% CI], 1.8-54.1; P = .008) and death (RH, 6.9; 95% CI, 1.1-43.8; P = .04). The results indicate that high levels of HIV-1 RNA at birth and during primary viremia are associated with early onset of symptoms and rapid disease progression to AIDS and death in perinatally infected children.

Acquired Immunodeficiency Syndrome↗

Identification of levels of maternal HIV-1 RNA associated with risk of perinatal transmission. Effect of maternal zidovudine treatment on viral load.

OBJECTIVE: To determine if there are levels of human immunodeficiency virus type 1 (HIV-1) associated with a high or low risk of perinatal transmission and to ascertain the mechanism by which zidovudine treatment reduces perinatal transmission. DESIGN: A nonrandomized prospective cohort study. SETTING: University medical center and two general hospital affiliates from May 1989 to September 1994. PATIENTS: Ninety-two HIV-1-seropositive women (95 pregnancies) and their 97 infants. INTERVENTION: Forty-two mothers (43 pregnancies) received zidovudine therapy during pregnancy and/or during labor and delivery. Eleven infants received prophylactic zidovudine for the first 6 weeks after delivery. MAIN OUTCOME MEASURE: HIV-1 infection status of the infant. RESULTS: Twenty of the 97 infants were perinatally infected with HIV-1. Transmitting mothers were more likely to have plasma HIV-1 RNA levels higher than 50000 copies per milliliter at delivery than nontransmitting mothers (15 [75.0%] of 20 transmitters vs four [5.3%] of 75 nontransmitters; P < .001). None of the 63 women with less than 20000 HIV-1 RNA copies per milliliter transmitted. Twenty-two women treated with open-label oral zidovudine during gestation showed an eightfold median decrease in plasma RNA levels (median [25th and 75th percentile], 43043 [5699 and 63053] copies per milliliter before zidovudine vs 4238 [603 and 5116] HIV-1 RNA copies per milliliter at delivery; P < .001) and none transmitted. Four zidovudine-treated women with high HIV-1 levels transmitted despite the presence of zidovudine-sensitive virus in vitro in both the mothers and their infants. CONCLUSIONS: Maternal HIV-1 RNA levels were highly predictive of perinatal transmission risk and suggest that certain levels of virus late in gestation and/or during labor and delivery are associated with both a high risk and a low risk of transmission. Our results also suggest that zidovudine exerts a major protective effect by reducing maternal HIV-1 RNA levels prior to delivery and that further strategies are needed to prevent perinatal transmission in women with high or increasing virus levels and/or zidovudine-resistant virus.

AIDS Serodiagnosis↗

Frequent recurrence and persistence of varicella-zoster virus infections in children infected with human immunodeficiency virus type 1.

OBJECTIVE: To examine complications and treatment of varicella-zoster virus (VZV) infections in children infected with human immunodeficiency virus type 1 (HIV-1). METHODS: Cases of VZV infection were identified retrospectively by reports to the department of health services and review of medical charts. The CD4+ cell counts were correlated with severity and frequency of VZV episodes. RESULTS: We identified 117 episodes of VZV infection in 73 HIV-1-infected children between Aug. 21, 1986, and Dec. 1, 1993. The most common complications were recurrence and persistence; 38 children (53%) had 69 recurrent episodes of VZV infection. The majority of children (61%) had zoster during the first recurrent episode, and 32% had a disseminated eruption typical of varicella. There was a strong association between an increasing number of episodes of VZV infection and low CD4+ cell count (p = 0.0008). In a subgroup followed for at least 2 years after their primary varicella episode, 10 of 22 children had a recurrence. Persistence of VZV infection was documented in 10 of 73 children, whereas other complications were rare. Thirty-three children (45%) were hospitalized and received acyclovir intravenously. CONCLUSION: Primary, recurrent, and persistent VZV infections are a frequent cause of morbidity and hospitalization for HIV-1-infected children. Studies of improved preventive and therapeutic agents are urgently needed in this population.

AIDS-Related Opportunistic Infections↗

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↗

Rapid increases in load of human immunodeficiency virus correlate with early disease progression and loss of CD4 cells in vertically infected infants.

The relationship between viral burden, timing of transmission, and clinical progression was investigated in 110 children at risk for vertical human immunodeficiency virus (HIV) infection using quantitative polymerase chain reaction, coculture, and immune complex-dissociated p24 antigen assay. In a cross-sectional study, the mean HIV DNA copy number in 19 symptomatic children was significantly higher than in 31 infected, asymptomatic children (420 +/- 125 vs. 87 +/- 78; P < .0001). In a second group of 8 vertically infected infants followed prospectively from birth, 4 defined as infected in utero showed a more rapid increase in virus load, an accelerated loss of CD4 cells, and early progression to symptomatic disease (3-12 weeks) compared with 4 children with late in utero or intrapartum transmission (10-31 months). These data suggest that a direct relationship exists between HIV replication, the timing of transmission and onset and progression of HIV disease in vertically infected children.

Acquired Immunodeficiency Syndrome↗

Functional activities of human antibody induced by the capsular polysaccharide or polysaccharide-conjugate vaccines against Haemophilus influenzae type b.

To determine the in vitro and in vivo activity of human antibody induced by different Haemophilus influenzae type b (Hib) vaccines, pooled human antisera obtained from adults immunized with either polyribosyl ribitol phosphate (PRP) or PRP-conjugated with diphtheria toxoid (PRP-D) vaccines were evaluated for opsonic and protective activity against Hib. In vitro, opsonophagocytic studies revealed that PRP-D induced antisera were approximately 2.5-fold more effective than PRP-induced antisera in supporting neutrophil-mediated killing of an Hib strain. In vivo studies using the infant rat model or Hib disease revealed that the decay of PRP antibody was similar with PRP or PRP-D induced antisera in unchallenged rats. However, in infant rats challenged with Hib, the PRP induced antibody decayed more rapidly than the PRP-D induced antibody as shown by significantly shorter half-life of the former. The protective efficacy was significantly greater with the PRP-D induced antisera than with the PRP induced antisera. This finding was shown by the significantly lower incidence of bacteraemia and the 5-fold lower dose of antibody required for 50% protection against bacteraemia in rats receiving the PRP-D induced antisera. The findings suggest that antibody to PRP induced by PRP-D vaccine is more opsonic and protective against Hib, and also decays more slowly in infant rats challenged with Hib than does antibody induced by PRP vaccine. Further studies are needed to elucidate the reason(s) for this difference in functional activity and in half-life of PRP antibody induced by PRP or by PRP-D vaccines.

Adult↗

Antimicrobial therapy of experimental group B streptococcal infection in mice.

Group B beta-hemolytic streptococci (GB-BHS) frequently cause severe infection in newborns. Previous in vitro studies showed accelerated killing of GB-BHS by ampicillin plus gentamicin as compared with ampicillin alone. To extend the in vitro observations, mice were infected experimentally with GB-BHS and treated with gentamicin plus ampicillin or ampicillin alone. Untreated mice died within 10 to 48 h. Compared with treatment with ampicillin alone, ampicillin-and-gentamicin therapy resulted in improved survival when the antibiotics were given in established infection or as a single dose at the time of infection. Ampicillin and gentamicin accelerated the clearing of bacteremia as compared with treatment with ampicillin alone. In view of these findings, the therapy of GB-BHS infection in newborns and other patients should be reconsidered in that a combination of ampicillin or penicillin G plus gentamicin might be superior to the use of ampicillin or penicillin G alone.

Ampicillin↗

Antibiotic-killing kinetics of group B streptococci.

Group B streptococci are uniformly susceptible to penicillin or ampicillin. Nevertheless, morbidity and mortality in newborn infants infected with group B streptococci is a major clinical problem. Bacteriologic determinants in the outcome of this infection were studied. Streptococcal killing kinetics were studied for ampicillin alone and in combination with gentamicin. In all cases killing was accelerated by the combination. The practice of discontinuing administration of the aminoglycoside antibiotic when group B streptococcal infection is confirmed should be re-evaluated.

Ampicillin↗

Alteration of lymphocyte subpopulations with cytomegalovirus infection in infancy.

The distribution of immunoglobulin bearing (Ig+), T, and null lymphocyte subpopulations and the lymphocyte response to phytohaemagglutinin (PHA) and pokeweed mitogen (PWM) were determined in three infants with cytomegalovirus (CMV) infection. These infants had significantly decreased percentages of T cells (13%, 29% and 40%) compared to age-matched controls (61 +/- 2%). Compensatory increases in the percentages of Ig+ and null cells occurred. Decreased lymphocyte reactivity to PHA and PWM occurred in two patients. Purified T cells from these patients had normal reactivity indicating a disproportion of T cells in the peripheral blood. These abnormalities may result from CMV infection of lymphocytes and could be responsible for prolonged CMV viruria.

Cytomegalovirus Infections↗

Factors predictive of maternal-fetal transmission of HIV-1. Preliminary analysis of zidovudine given during pregnancy and/or delivery.

OBJECTIVE: To assess maternal risk factors potentially influencing vertical transmission of human immunodeficiency virus, type 1 (HIV-1), including maternal CD4 cell count; presence of immune complex dissociated (ICD) p24 antigen; maternal zidovudine therapy during pregnancy and/or delivery; complications of pregnancy, such as preterm labor and birth; and obstetric events during labor and delivery, such as duration of labor, mode of delivery, chorioamnionitis, and maternal blood exposure. DESIGN AND SETTING: A nonrandomized prospective cohort study at a university medical center and two general hospital affiliates. PATIENTS: Sixty-three HIV-1-seropositive pregnant women and their 68 infants. INTERVENTION: Twenty-six mothers received zidovudine therapy during pregnancy and/or during labor and delivery. MAIN OUTCOME MEASURE: HIV-1 infection status of the infant. RESULTS: Thirteen of the 68 infants were vertically infected with HIV-1. Mothers with events involving fetal exposure to maternal blood were more likely to transmit infection (four [31%] of 13 vs three [5%] of 55, P = .02), as were women with plasma ICD p24 antigenemia at delivery (six [67%] of nine vs 11 [25%] of 44, P = .02). Zidovudine treatment was associated with a significant reduction in vertical transmission (one [4%] of 26 mothers treated with zidovudine vs 12 [29%] of 42 mothers not treated with zidovudine, P = .01). There was a significant protective effect of zidovudine treatment despite lower mean absolute CD4 cell counts (0.37 x 10(9)/L) in the 24 zidovudine-treated nontransmitters and in the nine non-zidovudine-treated transmitters (0.37 x 10(9)/L) than in the 24 non-zidovudine-treated nontransmitters (0.62 x 10(9)/L) (P = .008). CONCLUSION: Maternal-fetal HIV-1 transmission is multifactorial, with increased risk associated both with ICD p24 antigenemia at term and with intrapartum events that increase fetal exposure to maternal blood. Zidovudine therapy given during pregnancy and/or labor and delivery was associated with a significant reduction in vertical transmission. These data suggest that the beneficial effects of zidovudine therapy in reducing maternal-fetal HIV-1 transmission recently found in protocol 076 of the placebo-controlled Acquired Immunodeficiency Syndrome Clinical Trials Group Study may extend to women with lower CD4 cell counts and suggest that prolonged treatment of infants may not be necessary.

Adult↗