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Biomedical subjects

R Yogev

Publications and source records attributed to R Yogev.

At least 55 records · Page 3Linked to original sources
PubMed1998

Occupational sitting and low hip mineral density.

In order to evaluate the contribution of habitual physical activity to bone remodeling, we determined bone mineral density (BMD) at the lumbar spine (L2-4) and the hip by dual energy X-ray absorptiometry in 55 clerks and 44 nurses. Our data indicate similar L2-4 BMD in both groups due to equal weight load of the upper part of the body on the spinal column in both study groups, but higher femur BMD in the nurse group (0.6-0.8 SD, at various hip measurement sites) than in the clerk group. The age-adjusted hip BMD was correlated with serum osteocalcin levels, and was related to the duration of standing at work, indicating a cause and effect relationship. We conclude that prolonged working in a sitting position may induce a low hip BMD, and thereby increase the risk for osteoporotic hip fracture.

Adult↗
PubMed1998

A randomized study of combined zidovudine-lamivudine versus didanosine monotherapy in children with symptomatic therapy-naive HIV-1 infection. The Pediatric AIDS Clinical Trials Group Protocol 300 Study Team.

OBJECTIVE: The Pediatric AIDS Clinical Trials Group (PACTG) Protocol 300 assessed the clinical efficacy and safety of combination zidovudine/lamivudine (ZDV/3TC) compared with either didanosine (ddI) alone or combination ZDV/ddI. STUDY DESIGN: Children with symptomatic human immunodeficiency virus (HIV) infection, 6 weeks through 15 years of age, were stratified according to age and randomly assigned to receive ddI, ZDV/3TC, or ZDV/ddI. The primary endpoint was time to first progression of HIV disease or death. Enrollment in the ZDV/ddI arm stopped after 11 months on the basis of results of PACTG Protocol 152, but blinded follow-up continued. RESULTS: For the 471 children who could be evaluated, the median age was 2.7 years, median CD4 cell count was 699 cells/mm3, and median log10 HIV RNA was 5.1/mL. Median follow-up was 9.4 months. Patients receiving ZDV/3TC had a lower risk of HIV disease progression or death than those receiving ddI alone (15 vs 38 failures, P = .0006) and a lower risk of death (3 vs 15 deaths, P = .0039). Weight and height growth rates, CD4+ cell counts, and RNA concentrations showed results favoring ZDV/3TC. For patients concurrently randomized to all 3 treatment arms, both ZDV/3TC and ZDV/ddI recipients had lower risk of HIV disease progression than those who received ddI alone (P = .0026 and P = .0045). CONCLUSIONS: Combination therapy with either ZDV/3TC or ZDV/ddI was superior, as determined by clinical and laboratory measures, to monotherapy with ddI.

Adolescent↗
PubMed1998

Genetic diversity among Mycobacterium avium complex strains recovered from children with and without human immunodeficiency virus infection.

The genetic diversity and molecular epidemiology of Mycobacterium avium complex (MAC) infections in children with and without human immunodeficiency virus (HIV) infection were evaluated. Isolates recovered from 136 children were subtyped by sequence analysis of a 360-bp region of the gene (hsp65) encoding a 65-kDa heat-shock protein. Twenty-one distinct hsp65 alleles were identified. On the basis of hsp65 genotype, 6 isolates were not MAC organisms. Of the remaining 130 samples, 61% were M. avium, 37% were Mycobacterium intracellulare, and 2% were species nonspecific MAC. Eighty-eight percent of the isolates obtained from HIV-infected children were M. avium. In contrast, only 38% of the isolates obtained from children without HIV infection were M. avium (chi2 test, P < .001). M. avium isolates were further subtyped by Southern blot analysis with insertion element IS1245. Taken together, no evidence for a single clonal M. avium strain causing infection was detected.

AIDS-Related Opportunistic Infections↗
PubMed1998

Pharmacokinetics of nevirapine in human immunodeficiency virus type 1-infected pregnant women and their neonates. Pediatric AIDS Clinical Trials Group Protocol 250 Team.

The safety, toxicity, and pharmacokinetics of intrapartum and early newborn nevirapine were evaluated in 17 human immunodeficiency virus type 1-infected women in labor and their newborns. No adverse effects of nevirapine were noted in any study mothers or infants. Following maternal dosing with 200 mg during labor, concentrations exceeding 100 ng/mL (10 times the in vitro IC50) were achieved in the newborns. Nevirapine elimination was prolonged in both mothers and infants, with median half-lives ranging from 36.8 to 65.7 h. Administration of 200 mg orally to the mothers in labor and of a single 2-mg/kg oral dose to the infants at 48-72 h after birth maintained serum concentrations in the infants > 100 ng/mL through 7 days of life.

Adult↗
PubMed1998

HIV viral load.

Explore the source record for details and available documents.

Adolescent↗
PubMed1998

Characteristics of acute pneumonia in human immunodeficiency virus-infected children and association with long term mortality risk. National Institute of Child Health and Human Development Intravenous Immunoglobulin Clinical Trial Study Group.

OBJECTIVE: To describe the epidemiologic, clinical, radiologic, laboratory and treatment characteristics of acute pneumonia and its association with mortality in HIV-infected children. METHODS: Data were collected during a trial of intravenous immunoglobulin (IVIG) for infection prophylaxis (1988 to 1991); CD4+ percentage was measured and HIV RNA was assessed on stored sera collected at baseline and every 3 months. Mortality was recorded during the trial and updated through 1996. All reported physician-diagnosed pneumonia episodes underwent blinded review for trial endpoint classification as acute (new radiologic findings and presence of clinical symptoms) or nonacute. RESULTS: On blinded clinical trial endpoint review of all reported pneumonia episodes (n = 281), only 47% were classified as acute. One hundred thirty-one episodes of acute pneumonia were reported in 93 children (47 in 31 IVIG and 84 in 62 placebo patients, P < 0.01). The incidence of acute pneumonia was 24 episodes per 100 patient years. Findings associated with an acute bacterial process were uncommon (leukocytosis > or =15000/mm3 in 21% and fever > or =103 degrees F in 32% of episodes). Multiple acute episodes occurred in 34% of the children and were associated with increased risk of mortality in a univariate analysis (risk ratio, 2.1; 95% confidence interval, 1.3 to 3.4, P = 0.002), but in a multivariate model only baseline HIV RNA copy number and CD4+ percentage remained independently associated with mortality (relative risk, 2.0 and 1.4, respectively, P < 0.001). CONCLUSION: Acute pneumonia was a common occurrence in HIV-infected children and was associated with long term mortality risk. Multiple episodes of acute pneumonia likely represent a marker of progressive disease and immunologic dysfunction rather than being causally associated with increased long term mortality.

AIDS-Related Opportunistic Infections↗
PubMed1998

Phase I safety and pharmacokinetics study of micronized atovaquone in human immunodeficiency virus-infected infants and children. Pediatric AIDS Clinical Trials Group.

A phase I dose-escalating safety and pharmacokinetic study evaluated an oral suspension of micronized atovaquone (m-atovaquone) in infants and children stratified into age groups from 1 month to 12 years of age. Dosages of 10, 30, and 45 mg/kg of body weight/day were evaluated as single daily doses over a period of 12 days. Steady-state concentrations in plasma were determined on day 12, and single postdose concentrations were measured on days 1, 3, 5, 7, 9, 13, 15, 18, 21, and 24. Prior studies with adults suggest that the average plasma atovaquone concentration of 15 micrograms/ml is associated with therapeutic success in more than 95% of patients with Pneumocystis carinii pneumonitis. The results showed m-atovaquone to be safe and well tolerated. Dosages of 30 mg/kg/day were adequate to achieve an average steady-state concentration of greater than 15 micrograms/ml in children ages 1 to 3 months and 2 to 12 years, but a dosage of 45 mg/kg/day was needed to reach this concentration in infants 3 to 24 months of age. The oral suspension of atovaquone is safe and well tolerated in children. A single daily dose of 30 mg/kg provides bioavailability considered adequate for therapy of P. carinii pneumonia, but infants between 3 and 24 months of age may require a dosage of 45 mg/kg/day.

AIDS-Related Opportunistic Infections↗
PubMed1998

Quantification of human immunodeficiency virus type 1 RNA levels in plasma by using small-volume-format branched-DNA assays.

We have developed small-volume (50 or 250 microl)-format branched-DNA assays for human immunodeficiency virus type 1 (HIV-1) RNA for use with specimens in which the volume is limited and/or a high viral load is anticipated. These formats exhibited good correlation with the standard 1-ml format; high specificity, reproducibility, and linearity; and no significant difference in the quantification of HIV-1 subtypes.

Adolescent↗
PubMed1998

A randomized comparative trial of stavudine (d4T) versus zidovudine (ZDV, AZT) in children with human immunodeficiency virus infection. AIDS Clinical Trials Group 240 Team.

OBJECTIVES: To compare the safety and tolerance of stavudine (d4T) versus zidovudine (ZDV, AZT) in symptomatic human immunodeficiency virus-infected children 3 months to 6 years of age. METHODS: In an initially double-blind trial, 212 evaluable human immunodeficiency virus-infected children who had received no more than 6 weeks of previous antiretroviral therapy were randomized to receive either d4T (1 mg/kg orally every 12 hours, maximum 40 mg orally every 12 hours) or zidovudine (180 mg/m2 orally every 6 hours, maximum 200 mg orally every 6 hours). The study was unblinded after a median follow-up period of 6.3 months; median follow-up at study closure was 17.3 months. Tolerance, safety, disease progression, and immunologic responses were evaluated. RESULTS: The patient population was young (median age, 1.2 years; range, 0.3 to 6.4 years), with a median baseline CD4+ lymphocyte count of 965 cells/microL (range, 18 to 4238 cells/microL). Neutropenia < 400/microL occurred significantly more commonly among zidovudine recipients (1-year event rates of 20% both up to the time of unblinding and throughout the entire study) than among children receiving d4T (1-year event rates of 5% up to the time of unblinding and 6% throughout the entire study). In exploratory activity analyses using all data collected until study closure, children treated with d4T showed consistently greater positive changes from baseline in weight-for-age-and-gender z scores. As expected in this population of young children, median absolute CD4+ lymphocyte counts decreased in both treatment groups. Smaller changes from baseline were noted among d4T recipients. CONCLUSIONS: In children between the ages of 3 months and 6 years, d4T and zidovudine are largely comparable in terms of safety and tolerance. Neutropenia occurs significantly less commonly among children treated with d4T. There was evidence that weight gain and absolute CD4+ lymphocyte counts were better maintained in children receiving d4T.

Anti-HIV Agents↗
PubMed1998

Three-year multicenter surveillance of systemic pneumococcal infections in children.

OBJECTIVE: To track antibiotic susceptibility of Streptococcus pneumoniae isolates obtained from children with systemic infections and determine outcome of treatment. DESIGN: A 3-year (September 1993 through August 1996) prospective surveillance study of all invasive pneumococcal infections in children. PATIENTS: Infants and children cared for at eight children's hospitals in the United States with culture-proven systemic pneumococcal infection. RESULTS: One thousand two hundred ninety-one episodes of systemic pneumococcal infection were identified in 1255 children. An underlying illness was present in the children for 27% of the episodes. The proportion of isolates that were nonsusceptible to penicillin or ceftriaxone increased annually and nearly doubled throughout the 3-year period; for the last year the percentages of isolates nonsusceptible to penicillin and ceftriaxone were 21% and 9.3%, respectively. There was no difference in mortality between patients with penicillin-susceptible or nonsusceptible isolates. Only 1 of 742 patients with bacteremia had a repeat blood culture that was positive > 1 day after therapy was started. All 24 normal children with bacteremia attributable to isolates resistant to penicillin had resolution of their infection; the most common treatment regimen was a single dose of ceftriaxone followed by an oral antibiotic. CONCLUSIONS: The percentage of pneumococcal isolates nonsusceptible to penicillin and ceftriaxone increased yearly among strains recovered from children with systemic infection. Because empiric antibiotic therapy already has changed for suspected pneumococcal infections, antibiotic resistance has not been associated with increased mortality. Careful monitoring of antibiotic susceptibility and outcome of therapy is necessary to continually reassess current recommendations for treatment.

Adolescent↗
PubMed1998

Three-year multicenter surveillance of pneumococcal meningitis in children: clinical characteristics, and outcome related to penicillin susceptibility and dexamethasone use.

OBJECTIVES: To evaluate the antibiotic susceptibility of Streptococcus pneumoniae isolates obtained from the blood and cerebrospinal fluid of children with meningitis. To describe and compare the clinical and microbiological characteristics, treatment, and outcome of children with meningitis caused by S pneumoniae based on antimicrobial susceptibility of isolates and the administration of dexamethasone. DESIGN AND PATIENTS: Children with pneumococcal meningitis were identified from among a group of patients with systemic infections caused by S pneumoniae who were enrolled prospectively in the United States Pediatric Multicenter Pneumococcal Surveillance Study at eight children's hospitals in the United States. From September 1, 1993 to August 31, 1996, 180 children with 181 episodes of pneumococcal meningitis were identified and data were collected by retrospective chart review. OUTCOME: Clinical and laboratory characteristics were assessed. All pneumococcal isolates were serotyped and antibiotic susceptibilities for penicillin and ceftriaxone were determined. Clinical presentation, hospital course, and outcome parameters at discharge were compared between children infected with penicillin-susceptible isolates and those with nonsusceptible isolates and for children who did and did not receive dexamethasone. RESULTS: Fourteen (7.7%) of 180 children died; none of the fatalities were because of a documented failure of treatment caused by a resistant strain. Only 1 child, who had mastoiditis and a lymphangioma, experienced a bacteriologic failure with a penicillin-resistant (minimum inhibitory concentration = 2 microgram/mL) organism. Of the 166 surviving children, 41 (25%) developed neurologic sequelae (motor deficits) and 48 (32%) of 151 children had unilateral (n = 26) or bilateral (n = 22) moderate to severe hearing loss at discharge. Overall, 12.7% and 6.6% of the pneumococcal isolates were intermediate and resistant to penicillin and 4.4% and 2.8% were intermediate and resistant to ceftriaxone, respectively. Clinical presentation, cerebrospinal fluid indices on admission, and hospital course, morbidity, and mortality rates were similar for patients infected with penicillin- or ceftriaxone-susceptible versus nonsusceptible organisms. However, the relatively small numbers of nonsusceptible isolates and the inclusion of vancomycin in the treatment regimen for the majority of the patients limit the power of this study to detect significant differences in outcome between patients infected with susceptible and nonsusceptible isolates. Nonetheless, our results show that the nonsusceptible organisms do not seem to be intrinsically more virulent. Forty children (22%) received dexamethasone (>/=8 doses) initiated before or within 1 hour after the first dose of antibiotics. The incidence of any moderate or severe hearing loss was significantly higher in the dexamethasone group (46%) compared with children not receiving any dexamethasone (23%). The incidence of any neurologic deficits, including hearing loss, also was significantly higher in the dexamethasone group (55% vs 33%). However, children in the dexamethasone group more frequently required intubation and mechanical ventilation and had lower initial concentration of glucose in the cerebrospinal fluid than children who did not receive any dexamethasone. When we controlled for the confounding factor, severity of illness (intubation), the incidence of any deafness and of any neurologic sequelae, including deafness, were no longer significantly different between children who did or did not receive dexamethasone. CONCLUSIONS: Children with pneumococcal meningitis caused by penicillin- or ceftriaxone-nonsusceptible organisms and those infected by susceptible strains had similar clinical presentation and outcome. The use of dexamethasone was not associated with a beneficial effect in this retrospective and nonrandomized study. (ABSTRACT TRUNCATED)

Adolescent↗
PubMed1998

Clinical characteristics and outcome of children with pneumonia attributable to penicillin-susceptible and penicillin-nonsusceptible Streptococcus pneumoniae.

OBJECTIVE: To compare the clinical characteristics, treatment, and outcome of pediatric patients with pneumonia attributable to isolates of Streptococcus pneumoniae that were either susceptible or nonsusceptible to penicillin. DESIGN: Multicenter, retrospective study. SETTING: Eight children's hospitals in the United States. PARTICIPANTS: Two hundred fifty-four children with pneumococcal pneumonia identified from patients enrolled in the United States Pediatric Multicenter Pneumococcal Surveillance Study during the 3-year period from September 1, 1993 to August 31, 1996. OUTCOME MEASURES: Demographic and clinical variables including necessity for and duration of hospitalization, frequency of chest tube placement, antimicrobial therapy, susceptibility of isolates, and clinical outcome. RESULTS: There were 257 episodes of pneumococcal pneumonia that occurred in 254 patients. Of the 257 isolates, 22 (9%) were intermediate and 14 (6%) were resistant to penicillin; 7 (3%) were intermediate to ceftriaxone and 5 (2%) were resistant to ceftriaxone. There were no differences noted in the clinical presentation of the patients with susceptible versus nonsusceptible isolates. Twenty-nine percent of the patients had a pleural effusion. The 189 (74%) hospitalized patients were more likely to have an underlying illness, multiple lung lobe involvement, and the presence of a pleural effusion than nonhospitalized patients. Fifty-two of 72 hospitalized patients with pleural effusions had a chest tube placed, and 27 subsequently underwent a decortication drainage procedure. Eighty percent of the patients treated as outpatients and 48% of the inpatients received a parenteral second or third generation cephalosporin followed by a course of an oral antimicrobial agent. Two hundred forty-eight of the patients (97.6%) had a good response to therapy. Six patients died; however, only 1 of the deaths was related to the pneumococcal infection. CONCLUSION: The clinical presentation and outcome of therapy did not differ significantly between patients with penicillin-susceptible versus those with nonsusceptible isolates of S pneumoniae. Hospitalized patients were more likely to have underlying illnesses, multiple lobe involvement, and the presence of pleural effusions than patients who did not require hospitalization. In otherwise normal patients with pneumonia attributable to penicillin-resistant pneumococcal isolates, therapy with standard beta-lactam agents is effective.

Adolescent↗
PubMed1997

Medical students act as Big Brothers/Big Sisters to support human immunodeficiency virus-infected children's psychosocial needs.

OBJECTIVE: To address the special psychosocial and emotional needs and concerns of human immunodeficiency virus-infected children through a medical student-based Big Brother/Big Sister program. DESIGN: A telephone survey of 9 medical students who participated in the program in the last 4 years was undertaken to assess their experiences and feelings about the program. RESULTS: The experiences resulting from participation in the program were unanimously positive. The medical students stated that in no other medical setting were they able to develop a better understanding of the feelings and emotions of living with a terminal illness. The volunteers also believed that the program increased the benefits for the child and the medical student. CONCLUSIONS: Initial evaluation of the Big Brother/Big Sister program for human immunodeficiency virus-infected children suggests that it helped establish a strong, supportive relationship between the affected child and the medical student. A modified program in other medical schools may help to serve many other communities affected by the human immunodeficiency virus epidemic.

Adult↗
PubMed1997

Evaluation of pharmacokinetics, safety, tolerance, and activity of combination of zalcitabine and zidovudine in stable, zidovudine-treated pediatric patients with human immunodeficiency virus infection. AIDS Clinical Trials Group Protocol 190 Team.

A double-blind phase II trial compared zalcitabine (0.03 mg/kg/day) in combination with zidovudine (720 mg/m2/day) and zidovudine monotherapy in 250 clinically stable, previously zidovudine-treated, human immunodeficiency virus-infected children. The combination was well-tolerated except for an increased incidence of neutropenia (14%) compared with that in children receiving monotherapy (5%). No differences were noted for time to first AIDS-defining illness or death, neuropsychologic status, or weight Z scores. In patients in the combination arm, the CD4 cell count decline was slower (13% per year) than in patients receiving monotherapy (25% per year) (P = .03), and quantitative peripheral blood mononuclear cell virus load remained lower at all time points (P = .08). Deaths were fewer in patients receiving combination therapy (4) compared with those in patients receiving monotherapy (10) (P = .083). Thus, administration of zidovudine with zalcitabine to children with prior zidovudine treatment did not result in a significant increase in toxicity compared with that resulting from zidovudine monotherapy and demonstrated improvement in immunologic and virologic surrogate markers.

AIDS-Related Opportunistic Infections↗
PubMed1997

Megestrol acetate treatment of growth failure in children infected with human immunodeficiency virus.

OBJECTIVE: To evaluate the effect of megestrol acetate on weight gain and linear growth in human immunodeficiency virus-infected children with growth failure. METHODS: All human immunodeficiency virus-infected children with growth failure treated with megestrol acetate at our institution were evaluated retrospectively. Weight, height, and weight:height ratio were documented from 6 months before initiation of megestrol acetate until 6 months after treatment was discontinued. Measurements were corrected for age and sex by conversion to z-scores. Incremental growth was determined before, during, and after treatment. The potential effects of CD4+ T-lymphocyte count and percentage, antiretroviral therapy, and intercurrent illnesses on growth were evaluated. RESULTS: Nineteen patients were treated with a total of 27 courses of megestrol acetate. The median duration of therapy was 7 months (range, 3 to 11 months), and the median megestrol acetate dose was 7.91 mg/kg/day (range, 4.06 to 8.56 mg/kg/day). From 6 months and 3 months before treatment to the onset of therapy, median changes in weight z-scores were -.27 and -.15, respectively. During megestrol acetate treatment, median changes in weight z-scores were +.29 after 1 month of therapy, +.40 after 3 months, and +.57 after 6 months. After megestrol acetate therapy was discontinued, poor weight gain and weight loss resumed. Median 6-month growth velocities for weight were less than the 10th percentile before megestrol acetate, greater than the 97th percentile during treatment, and less than the 3rd percentile after treatment was discontinued. Megestrol acetate therapy was not associated with changes in linear growth. Antiretroviral therapy, CD4+ T-lymphocyte count or percentage, or intercurrent illnesses were not associated with statistically significant differences in response to megestrol acetate therapy. CONCLUSIONS: Megestrol acetate treatment of growth failure in pediatric human immunodeficiency virus disease is associated with weight gain, without affecting linear growth.

Adolescent↗
PubMed1996

Randomized study of the tolerance and efficacy of high- versus low-dose zidovudine in human immunodeficiency virus-infected children with mild to moderate symptoms (AIDS Clinical Trials Group 128). Pediatric AIDS Clinical Trials Group.

The current dosage of zidovudine for children is 180 mg/m2 every 6 h. To investigate whether a lower dosage was equally effective, human immunodeficiency virus (HIV)-infected children (3 months to 12 years) with mild to moderate symptoms were randomly assigned to receive either high-dose (180 mg/m2/dose) or low-dose (90 mg/m2/dose) zidovudine (double-blind). Treatments were compared with respect to neuropsychologic function, survival, clinical and laboratory evidence of disease progression, and safety and tolerance. Four hundred twenty-six HIV-infected children were enrolled; median time for receipt of study drug was 35 months. Zidovudine in either dose was well tolerated, with no difference in efficacy or tolerance by treatment group using any clinical or laboratory parameter. In children with mild to moderate disease, a reduction of zidovudine to 90 mg/m2/dose will result in substantial cost savings and should be the recommended dose.

AIDS Dementia Complex↗
PubMed1996

Effect of human immunodeficiency virus type 1 protein R (vpr) gene expression on basic cellular function of fission yeast Schizosaccharomyces pombe.

The human immunodeficiency virus type 1 (HIV-1) Vpr protein affects cell morphology and prevents proliferation of human cells by induction of cell cycle G2 arrest. In this study, we used the fission yeast Schizosaccharomyces pombe as a model system to investigate the cellular effects of HIV-1 vpr gene expression. The vpr gene was cloned into an inducible fission yeast gene expression vector and expressed in wild-type S. pombe cells, and using these cells, we were able to demonstrate the specific Vpr-induced effects by induction and suppression of vpr gene expression. Induction of HIV-1 vpr gene expression affected S. pombe at the colonial, cellular, and molecular levels. Specifically, Vpr induced small-colony formation, polymorphic cells, growth delay, and cell cycle G2 arrest. Additionally, Vpr-induced G2 arrest appeared to be independent of cell size and morphological changes. The cell cycle G2 arrest correlated with increased phosphorylation of p34cdc2, suggesting negative regulation of mitosis by HIV-1 Vpr. Treatment of Vpr-induced cell with a protein phosphatase inhibitor, okadaic acid, transiently suppressed cell cycle arrest and morphological changes. This observation implicates possible involvement of protein phosphatase(s) in the effects of Vpr. Together, these data showed that the HIV-1 Vpr-induced cellular changes in S. pombe are similar to those observed in human cells. Therefore, the S. pombe system is suited for further investigation of the HIV-1 vpr gene functions.

CDC2 Protein Kinase↗