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Biomedical subjects

R Yogev

Publications and source records attributed to R Yogev.

At least 37 records · Page 2Linked to original sources
PubMed2000

CD8+ T cell-mediated suppression of human immunodeficiency virus replication in older children with acquired immunodeficiency syndrome.

BACKGROUND: Suppression of HIV replication by CD8+ T cells and/or their products correlated with the survival of infants. We sought to elucidate the role of CD8+ T cell-mediated suppression in seven older children with AIDS. METHODS: After separation of each child's CD4+ and CD8+ T cells, three different HIV culture assays were performed: (1) patient CD4+ T cells and phytohemagglutinin (PHA)-stimulated donor peripheral blood mononuclear cells (PBMC); (2) patient CD8+ T cells added to the CD4+ T cells and the PHA-stimulated donor PBMC (to test for CD8-mediated T cell suppression of HIV); (3) patient CD8+ cells added across a semipermeable membrane to the CD4+ T cells and the PHA-stimulated donor PBMC [to determine whether the CD8 cells secreted a soluble factor(s) that suppressed HIV]. RESULTS: Cultures from four of seven children showed greater HIV replication with CD4 cells alone than with CD4 and CD8 cells together, demonstrating CD8 suppression; evidence of soluble suppression was also seen. Cultures from two of the seven children showed HIV replication and no evidence of CD8 cell suppression. Cultures from one of the seven children had no appreciable replication of HIV even after removal of CD8 cells. CONCLUSIONS: CD8-mediated suppression is present in at least some children with AIDS. Additional mechanisms may be operating to slow the progression of the disease.

CD4-Positive T-Lymphocytes↗
PubMed2000

Gastrostomy tube insertion for improvement of adherence to highly active antiretroviral therapy in pediatric patients with human immunodeficiency virus.

OBJECTIVES: Newer combination antiretroviral therapies used to treat human immunodeficiency virus (HIV)-infected individuals have resulted in dramatic delays in HIV progression, with reduction in mortality and morbidity. However, adherence to highly active antiretroviral therapy (HAART) may be problematic, particularly in HIV-infected children. Reasons for nonadherence include refusal, drug tolerability, and adverse reactions. We assess: 1) the potential benefits of gastrostomy tube (GT) for the improvement of adherence to HAART in HIV-infected children, and 2) the factors that may result in improved viral suppression after GT placement. METHODS: The medical records of 17 pediatric HIV-infected patients, in whom GT was used to improve HAART adherence, were retrospectively reviewed for clinical and laboratory parameters. Each record was reviewed for the period of 1 year before and after GT insertion. The main outcome parameters were virologic (plasma HIV RNA polymerase chain reaction quantification) and immunologic (CD4 cell counts). Documentation of adherence to medications in medical records was also assessed during the study. Parental questionnaires were used to determine GT satisfaction and medication administration times. The Wilcoxon rank sum test was used to assess change in viral load (VL) and CD4 cell percentages. RESULTS: GT was well-tolerated with minor complications, such as local site tenderness, reported by 4 patients (23%). Before GT insertion, only 6 patients (35%) were documented as being adherent, compared with all patients after GT insertion. Ten patients (58%) had >/=2 log(10) VL decline after GT insertion (median: 3.2 log(10)), compared with 7 patients (42%) who had </=2 log(10) VL decline (median: 1.27 log(10)). Both groups of patients (responders and nonresponders) did not differ significantly in baseline parameters, such as VL, CD4 cell percentages, or previous drug therapy. However, in all 10 patients with >/=2 log(10) VL decline, therapy was changed at the time of or soon after GT insertion (median:.8 months; range: 0-6 months), compared with 7 patients with <2 log(10) VL decline who had therapy changed before GT insertion (median: 3.2 months; range: 1-8 months). Parental questionnaires reported significantly shorter medication administration times after GT insertion, with 70% of patients taking >5 minutes before GT, compared with 0% after GT. Questionnaires indicated satisfaction with GT, with perceived benefits being reduced medication administration time and improved behavior surrounding taking medications. CONCLUSIONS: GT is well-tolerated in pediatric HIV-infected patients and should be considered for selected patients to overcome difficulties with medication administration and to improve adherence. For maximal virologic response, combination therapy should be changed at the time of GT insertion.

Anti-HIV Agents↗
PubMed2000

Pneumococcal mastoiditis in children.

OBJECTIVE: To determine the impact of antibiotic resistance on the frequency, clinical features, and management/outcome of mastoiditis attributable to Streptococcus pneumoniae. DESIGN: Retrospective review of the medical records of children with mastoiditis caused by S pneumoniae from September 1993 through December 1998. PATIENTS: Infants and children with pneumococcal mastoiditis cared for at 8 children's hospitals in the United States. RESULTS: Thirty-four children with pneumococcal mastoiditis were identified. The median age of the children was 12 months (range: 2 months-12.5 years); 28 (82%) were </=2 years old. Six children had recurrent otitis media. A subperiosteal abscess was noted in 13 children (37%). The mastoids were abnormal in all 25 patients on whom computed tomography was performed. There was no trend toward increasing numbers of cases per year despite increasing proportions of pneumococcal isolates, which were nonsusceptible to penicillin. Serogroup 19 accounted for 57% of isolates, serogroup 23 for 14.3% of isolates, and serotype 3 for 10. 7% of isolates. Except for receipt of less antibiotic therapy in the previous 30 days, children with penicillin-susceptible isolates had similar demographic features and clinical findings and surgical treatment as did children whose isolates were nonsusceptible to penicillin. CONCLUSIONS: Pneumococcal mastoiditis occurs primarily in children <2 years of age and usually is not associated with a history of recurrent otitis media. The number of cases of mastoiditis caused by S pneumoniae occurring among 8 children's hospitals has remained stable despite increasing rates of antibiotic-resistant S pneumoniae. Serogroup 19 is the leading serogroup associated with pneumococcal mastoiditis. Streptococcus pneumoniae, mastoiditis, serotypes, resistance.

Cephalosporin Resistance↗
PubMed2000

Pneumococcal facial cellulitis in children.

OBJECTIVE: To review the epidemiology and clinical course of facial cellulitis attributable to Streptococcus pneumoniae in children. DESIGN: Cases were reviewed retrospectively at 8 children's hospitals in the United States for the period of September 1993 through December 1998. RESULTS: We identified 52 cases of pneumococcal facial cellulitis (45 periorbital and 7 buccal). Ninety-two percent of patients were <36 months old. Most were previously healthy; among the 6 with underlying disease were the only 2 patients with bilateral facial cellulitis. Fever (temperature: >/=100.5 degrees F) and leukocytosis (white blood cell count: >15 000/mm(3)) were noted at presentation in 78% and 82%, respectively. Two of 15 patients who underwent lumbar puncture had cerebrospinal fluid with mild pleocytosis, which was culture-negative. All patients had blood cultures positive for S pneumoniae. Serotypes 14 and 6B accounted for 53% and 27% of isolates, respectively. Overall, 16% and 4% were nonsusceptible to penicillin and ceftriaxone, respectively. Such isolates did not seem to cause disease that was either more severe or more refractory to therapy than that attributable to penicillin-susceptible isolates. Overall, the patients did well; one third were treated as outpatients. CONCLUSIONS: Pneumococcal facial cellulitis occurs primarily in young children (<36 months of age) who are at risk for pneumococcal bacteremia. They present with fever and leukocytosis. Response to therapy is generally good in those with disease attributable to penicillin-susceptible or -nonsusceptible S pneumoniae. Ninety-six percent of the serotypes causing facial cellulitis in this series are included in the heptavalent-conjugated pneumococcal vaccine recently licensed in the United States.

Cellulitis↗
PubMed1999

Randomised trial of intradermal Mycobacterium vaccae or intradermal hepatitis B immunisation in children with HIV infection.

This study assessed the safety of inactivated Mycobacterium vaccae as a candidate vaccine to prevent disseminated mycobacterial disease in children with HIV infection. 35 children ages 1-8 with CD4 counts > or =300/mm3 in New Hampshire, Boston and Chicago were randomised in a 2:1 schedule to receive a 3-dose series of intradermal M. vaccae vaccine (MV) or hepatitis B vaccine (HBV) at 2-month intervals. Immunisation was safe and well tolerated; 2-day median vaccine site in duration was 5 mm in MV recipients and 0 mm in HBV recipients (p < 0.001). There were no significantly different changes in viral load or CD4 count between the two vaccine groups. No PPD skin test conversions occurred after immunisation. MV is safe and well tolerated and deserves further evaluation as a vaccine to prevent mycobacterial disease in HIV-infected children.

Administration, Cutaneous↗
PubMed1999

Comparison of a beta-lactam alone versus beta-lactam and an aminoglycoside for pulmonary exacerbation in cystic fibrosis.

UNLABELLED: We determined whether a beta-lactam and an aminoglycoside have efficacy greater than a beta-lactam alone in the management of a pulmonary exacerbation in patients with cystic fibrosis. STUDY DESIGN: Azlocillin and placebo or azlocillin and tobramycin were administered to 76 patients with a pulmonary exacerbation caused by Pseudomonas aeruginosa in a randomized double-blind, third-party monitored protocol. Improvement was assessed by standardized clinical evaluation, pulmonary function testing, sputum bacterial density, sputum DNA content, and time to the next pulmonary exacerbation requiring hospitalization. RESULTS: No significant difference was seen between the 2 treatment groups in clinical evaluation, sputum DNA concentration, forced vital capacity, forced expiratory volume in second 1, or peak expiratory flow rate at the end of treatment (33 receiving azlocillin alone and 43 both antibiotics); adverse reactions were equivalent in each group. Sputum P. aeruginosa density decreased more with combination therapy (P =.034). On follow-up evaluation, an average of 26 days after the end of treatment, all outcome indicators had worsened in both groups. Time to readmission for a new pulmonary exacerbation was significantly longer in the group receiving azlocillin plus tobramycin (P <.001). Treatment-emergent tobramycin resistance occurred in both groups and was more frequent with combination therapy. CONCLUSION: We conclude that the combination of a beta-lactam and an aminoglycoside produces a longer clinical remission than a beta-lactam alone and slightly better initial improvement.

Adolescent↗
PubMed1999

Adrenal suppression in children with the human immunodeficiency virus treated with megestrol acetate.

Symptoms and laboratory evidence of adrenal suppression developed in 2 children with the human immunodeficiency virus after megestrol acetate (MA) therapy was discontinued; both required transient glucocorticoid replacement therapy. High-dose corticotropin stimulation testing performed on children with the human immunodeficiency virus treated or not treated with MA showed that baseline and post-corticotropin cortisol levels were extremely low in 7 of 10 treated patients and normal in 10 of 10 members of a control group (P <.01). MA may suppress adrenal function, and replacement glucocorticoids may prevent or relieve associated symptoms at times of severe stress or on discontinuation of MA therapy.

Adrenal Insufficiency↗
PubMed1999

Toxicity and efficacy of daily vs. weekly dapsone for prevention of Pneumocystis carinii pneumonia in children infected with human immunodeficiency virus. ACTG 179 Study Team. AIDS Clinical Trials Group.

BACKGROUND: Dapsone is an alternative drug for Pneumocystis carinii pneumonia (PCP) prophylaxis in individuals intolerant to trimethoprim-sulfamethoxazole (T/S). There are, however, few data on the pharmacokinetics, toxicity or efficacy of dapsone in children. Design. Randomized, multicenter trial comparing daily (1 or 2 mg/kg) with weekly (4 mg/kg) dapsone regimens in 94 HIV-infected children intolerant to T/S. METHODS: Hematologic and hepatic toxicity was monitored, as well as the occurrence of skin rash, PCP or death. RESULTS: Initial pharmacokinetic data indicated that adequate serum dapsone concentrations were not achieved with the daily 1-mg/kg regimen; the daily dose was then increased to 2 mg/kg. Both short and long term hematologic toxicities were marginally greater in children receiving the daily 2 mg/kg compared with the weekly regimen. Allergic skin rashes were similar in children receiving the daily and weekly regimens (17% in both) and were not associated with prior history of rash with T/S. PCP occurred most frequently with the daily 1-mg/kg regimen (22.0 cases/100 patient years), least frequently with the daily 2-mg/kg regimen (0 case/100 patient years) and at intermediate frequency with the weekly regimen (9.5 cases/100 patient years). More deaths were observed in patients receiving the daily than the weekly regimen (8 vs. 2, respectively), although the deaths were not directly attributable to dapsone treatment. CONCLUSION: Although a weekly dapsone regimen of 4 mg/kg produced less hematologic toxicity than a daily regimen of 2 mg/kg, this advantage was offset by a trend toward higher breakthrough rates of PCP.

AIDS-Related Opportunistic Infections↗
PubMed1999

Safety and single-dose pharmacokinetics of abacavir (1592U89) in human immunodeficiency virus type 1-infected children.

Abacavir (formerly 1592U89) is a potent 2'-deoxyguanosine analog reverse transcriptase inhibitor that has been demonstrated to have a favorable safety profile in initial clinical trials with adults with human immunodeficiency virus (HIV) type 1 infection. A phase I study was conducted to evaluate the pharmacokinetics and safety of abacavir following the administration of two single oral doses (4 and 8 mg/kg of body weight) to 22 HIV-infected children ages 3 months to 13 years. Plasma was collected for analysis at predose and at 0.5, 1, 1.5, 2, 2.5, 3, 5, and 8 h after the administration of each dose. Plasma abacavir concentrations were determined by high-performance liquid chromatography, and data were analyzed by noncompartmental methods. Abacavir was well tolerated by all subjects. The single abacavir-related adverse event was rash, which occurred in 2 of 22 subjects. After administration of the oral solution, abacavir was rapidly absorbed, with the time to the peak concentration in plasma occurring within 1.5 h postdosing. Pharmacokinetic parameter estimates were comparable among the different age groups for each dose level. The mean maximum concentration in plasma (Cmax) and the mean area under the curve from time zero to infinity (AUC0-infinity) increased by 16 and 45% more than predicted, respectively, as the abacavir dose was doubled from 4 to 8 mg/kg (Cmax increased from 1.69 to 3.94 micrograms/ml, and AUC0-infinity increased from 2.82 to 8.09 micrograms.h/ml). Abacavir was rapidly eliminated, with a mean elimination half-life of 0.98 to 1.13 h. The mean apparent clearance from plasma decreased from 27.35 to 18.88 ml/min/kg as the dose increased. Neither body surface area nor creatinine clearance were correlated with pharmacokinetic estimates at either dose. The extent of exposure to abacavir appears to be slightly lower in children than in adults, with the comparable unit doses being based on body weight. In conclusion, this study showed that abacavir is safe and well tolerated in children when it is administered as a single oral dose of 4 or 8 mg/kg.

Adolescent↗
PubMed1999

Pharmacokinetics of azithromycin administered alone and with atovaquone in human immunodeficiency virus-infected children. The ACTG 254 Team.

To evaluate if atovaquone (ATQ) interacts pharmacokinetically with azithromycin (AZ) in human immunodeficiency virus-infected children, 10 subjects (ages, 4 to 13 years) were randomized in a crossover study to receive AZ (5 mg/kg/day) alone (ALONE) or AZ (5 mg/kg/day) and ATQ (30 mg/kg/day) simultaneously (SIM) prior to receiving AZ and ATQ staggered by 12 h. Despite a lack of significant difference in the mean AZ pharmacokinetic parameters, the steady-state values of AZ's area under the concentration-time curve from 0 to 24 h and maximum concentration in serum were consistently lower (n = 7 of 7) for the SIM regimen than they were for the ALONE regimen. A larger study will be required to determine if ATQ affects AZ pharmacokinetics and efficacy in a clinically significant manner.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Plasma-soluble CD30 in childhood tuberculosis: effects of disease severity, nutritional status, and vitamin A therapy.

Plasma-soluble CD30 (sCD30) is the result of proteolytic splicing from the membrane-bound form of CD30, a putative marker of type 2 cytokine-producing cells. We measured sCD30 levels in children with tuberculosis, a disease characterized by prominent type 1 lymphocyte cytokine responses. We postulated that disease severity and nutritional status would alter cytokine responses and therefore sCD30 levels. Samples from South African children enrolled prospectively at the time of diagnosis of tuberculosis were analyzed. (Patients were originally enrolled in a randomized, double-blind placebo-controlled study of the effects of oral vitamin A supplementation on prognosis of tuberculosis.) Plasma samples collected at the time of diagnosis and 6 and 12 weeks later (during antituberculosis therapy) were analyzed. sCD30 levels were measured by enzyme immunoassay. The 91 children included in the study demonstrated high levels of sCD30 at diagnosis (median, 98 U/liter; range, 11 to 1,569 U/liter). Although there was a trend toward higher sCD30 levels in more severe disease (e.g., culture-positive disease or miliary disease), this was not statistically significant. Significantly higher sCD30 levels were demonstrated in the presence of nutritional compromise: the sCD30 level was higher in patients with a weight below the third percentile for age, in those with clinical signs of kwashiorkor, and in those with a low hemoglobin content. There was minimal change in the sCD30 level after 12 weeks of therapy, even though patients improved clinically. However, changes in sCD30 after 12 weeks differed significantly when 46 patients (51%) who received vitamin A were compared with those who had received a placebo. Vitamin A-supplemented children demonstrated a mean (+/- standard error of the mean) decrease in sCD30 by a factor of 0.99 +/- 0.02 over 12 weeks, whereas a factor increase of 1.05 +/- 0.02 was demonstrated in the placebo group (P = 0.02). We conclude that children with tuberculosis had high sCD30 levels, which may reflect the presence of a type 2 cytokine response. Nutritional compromise was associated with higher sCD30 levels. Vitamin A therapy resulted in modulation of sCD30 levels over time.

Adolescent↗
PubMed1999

Central nervous system abnormalities in pediatric human immunodeficiency virus infection.

With the recent improvements in treatment of HIV, the disease has become a chronic one. The mean survival time of HIV-infected children is now 9-10 years, which is more than 4 times the mean age of such children who died in 1990. Yet, the prevalence of HIV encephalopathy has not decreased despite use of HAART. Rather, it is expected that as patients live longer, the prevalence of CNS manifestations will actually increase. Thus, more children can be expected to manifest encephalopathy, cerebral aneurysms and CNS lymphoma. As AIDS patients live longer, newer and more effective drugs to combat the neurological effects of HIV infection will be required. There is little evidence that HIV damages neurons directly; rather, the damage appears to occur indirectly via viral proteins or neurotoxic factors causing excessive stimulation by excitatory amino acids such as glutamate and quinolinate. This common pathway is similar to that seen in acute neuronal injury and CNS degenerative diseases and may make HIV encephalopathy amenable to pharmacotherapy. The very complexity of HIV CNS entry mechanisms and neuropathogenesis provides a host of sites for potential therapeutic interventions and hope for the future.

AIDS Dementia Complex↗
PubMed1999

Multiple recurrent gram-negative cerebrospinal fluid shunt infections associated with a patient with a retained ventricular foreign body.

A 3-year-old boy experienced 10 recurrent gram-negative ventriculoperitoneal shunt (VPS) infections with identical strains over a 17-month period. Multiple cranial MRI and CT scans to identify a retained foreign body were negative. CT myelography and pressure infusion radionuclide cisternography were also unhelpful. Ventriculoscopy revealed a small retained foreign body which was successfully removed, and cultures subsequently yielded gram-negative organisms identical to the previously identified bacteria by pulsed field gel electrophoresis. No further infections were noted after removal of the retained fragment. Exploratory ventriculostomy should be considered in patients with recurrent VPS infections where other techniques fail to reveal a cause.

Cerebral Ventricles↗
PubMed1999

Combination therapy with stavudine (d4T) plus didanosine (ddI) in children with human immunodeficiency virus infection. The Pediatric AIDS Clinical Trials Group 327 Team.

OBJECTIVES: To evaluate the safety, tolerance, and antiviral activity of combination therapy with stavudine (d4T) plus didanosine (ddI) in symptomatic human immunodeficiency virus (HIV)-infected children. METHODS: The study enrolled HIV-infected children who successfully completed Pediatric AIDS Clinical Trials Group (PACTG) protocol 240 (d4T versus zidovudine [ZDV] monotherapy) without disease progression or who had received ZDV monotherapy by prescription for at least the preceding 6 months. Children who had received d4T monotherapy in PACTG 240 were assigned to treatment with d4T plus ddI (arm 1). Children who had received ZDV monotherapy in PACTG 240 or by prescription were randomized in a double-blind manner to treatment with either d4T alone (arm 2) or d4T plus ddI (arm 3). Patients were followed for 48 weeks each. RESULTS: A total of 108 children were enrolled. The mean age was 5.0 years (range, 1. 6 to 11.5 years), with mean baseline plasma HIV RNA concentration and CD4(+) lymphocyte count of 4.6 log10 copies/mL (range, 2.6 to 5. 9 log10 copies/mL) and 819 cells/microL (range, 8 to 3431 cells/microL), respectively. Both d4T monotherapy and d4T plus ddI combination therapy were well-tolerated, with 96 (89%) patients completing 48 weeks of study treatment. Plasma HIV RNA concentrations showed larger average declines in arm 3 compared with arm 2 at study week 12 (0.49 vs 0.18 log10 copies/mL, respectively); these average declines were maintained through week 48 (0.51 vs 0.17 log10 copies/mL, respectively). Fewer than 8% of the patients in any of the treatment arms had plasma HIV RNA concentrations below the limit of quantification (200 copies/mL) at any time point. CONCLUSIONS: Combination therapy with d4T plus ddI is safe and well-tolerated in HIV-infected children, producing durable, but incomplete, suppression of virus replication. This combination of nucleoside antiretroviral agents may provide a valuable backbone to protease inhibitor-containing treatment regimens for HIV-infected children.

Anti-HIV Agents↗
PubMed1998

Safety and immunogenicity of HIV recombinant envelope vaccines in HIV-infected infants and children. National Institutes of Health-sponsored Pediatric AIDS Clinical Trials Group (ACTG-218).

Study objectives were to evaluate the safety and immunogenicity of three HIV recombinant glycoproteins in HIV-infected infants and children between 1 month and 18 years of age with asymptomatic (P-1) infection. Using Chiron rgp 120 (SF-2) 15 or 50 microg; MicroGeneSys rgp 160 (IIIB) 40 or 320 microg; Genentech rgp120 (MN) 75 or 300 microg; or adjuvant control (Alum or MF-59), children were randomized to a double-blind, placebo-controlled, dose-escalating study of vaccine administered intramuscularly at entry and 1, 2, 3, 4, and 6 months later. No adverse events were attributed to study vaccines. Between 30% and 56% of volunteers exhibited a lymphoproliferative response as defined in terms of stimulation index (SI) to vaccine antigens; 65% of vaccinees but none of placebo recipients exhibited moderate or strong responses after enzyme immunoassay to HIV specific antigens. CD4 cell counts and quantitative HIV culture did not differ significantly among vaccine and control groups, nor were differences found among groups in HIV disease progression. The rgp160 and gp120 subunit vaccines were safe and immunogenic in this population.

AIDS Vaccines↗
PubMed1998

Lymphocyte subpopulations in healthy 1-3-day-old infants.

The primary objective of this study was to establish reference ranges for the major (B, T, and natural killer; NK) and clinically relevant minor lymphocyte subsets in the peripheral blood of healthy 1-3-day-old infants and then to compare the results with those obtained in a group of healthy adults analyzed simultaneously. Forty-three infants aged 1-3 days and 38 healthy adults were recruited to the study to establish the median, 10th, and 90th percentiles of the proportions and absolute numbers of relevant lymphocyte subsets. The samples obtained from the healthy adults served as a flow cytometry process control in addition to providing a group comparator. The peripheral blood of the newborns (vs. adults) contained elevated proportions of total T cells (83% vs. 77%) and T helper cells (63% vs. 46%), with decreased proportions of T suppressor/cytotoxic cells (23% vs. 28%) and NK cells (4% vs. 10.5%). The newborns had a higher proportion (P < 0.0001) of immature B lymphocytes compared with those of adults (CD10+CD19+, 1.5% vs. 0% and CD20+CD5+, 13% vs. 6%), and the proportion of activated T cells was significantly lower (P < 0.0001; CD3+CD25+, 7.0% vs. 15%;CD3+HLA-DR+, 2.0% vs. 6% and CD8 and CD57, 0.0% vs. 8.0%). In contrast, the proportions of neonatal CD8 cells expressing CD28 (90.2% vs. 67.7%) and CD38 (96.6% vs. 70.9%) were significantly higher (P < 0.0001). The reference ranges for 1-3-day-old healthy newborns generated in this study provides a valuable tool for the assessment of immune abnormalities in very young infants.

Adult↗