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Biomedical subjects

R Yogev

Publications and source records attributed to R Yogev.

At least 19 recordsLinked to original sources
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↗
PubMed1995

Pediatric AIDS.

An estimated 1 million children worldwide have AIDS. Pediatricians should be aware of this disease and its many facets. This article provides information on the etiology and pathogenesis of AIDS in children, as well as its manifestations on the body. Prevention and clinical management are also reviewed.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Fever of unknown origin.

The causes of fever in a child can vary from minor brief illnesses to life-threatening infectious, malignant, or autoimmune diseases. The physician often has to evaluate children with fevers of as yet undiagnosed cause lasting fewer than 2 weeks, in whom it is important to determine whether localizing findings are present. Fever without localizing signs and fevers complicating chronic disease and resulting from specific localized infection are considered in the sections concerning infectious causes, immunodeficiency diseases, and rheumatic diseases. The diagnostic and therapeutic approaches to the child with both prolonged fever and fever of unknown origin are then discussed, with emphasis on rheumatic diseases.

Child↗
PubMed1995

Phase I evaluation of zalcitabine administered to human immunodeficiency virus-infected children.

The safety, tolerability, and pharmacokinetics of zalcitabine (ddC) in a single oral dose (0.02 mg/kg) was evaluated in 23 mildly symptomatic human immunodeficiency virus-infected children (mean age, 4.2 years). After administration of ddC, blood samples were obtained at 0.5, 1, 1.5, 2, 4, 6, and 8 h for analysis. The drug was well tolerated and no side effects were noted. Plasma ddC levels were determined by ion spray liquid chromatography/tandem mass spectrometry. ddC was rapidly absorbed, with a mean maximum plasma concentration of 9.3 ng/mL (range, 3.2-14.1) attained within a mean of 1 h (range, 0.5-2.0). Mean elimination half-life was 1.4 h (range, 1.0-3.5), mean area under the plasma concentration-time curve was 25 ng.h/mL (range, 11-37), and mean total body clearance was 14.6 mL/min/kg (range, 8.9-30.6). Plasma concentrations were lower and the half-life shorter in these children than in adults given comparable doses, suggesting that ddC may be cleared more rapidly in children than adults.

Adult↗
PubMed1995

Sequential, single-dose pharmacokinetic evaluation of meropenem in hospitalized infants and children.

Meropenem is a new carbapenem antibiotic which possesses a broad spectrum of antibacterial activity against many of the pathogens responsible for pediatric bacterial infections. In order to define meropenem dosing guidelines for children, an escalating, single-dose, pharmacokinetic study at 10, 20, and 40 mg/kg of body weight was performed. A total of 73 infants and children in four age groups were enrolled in the study: 2 to 5 months, 6 to 23 months, 2 to 5 years, and 6 to 12 years. The first patients enrolled were those in the oldest age group, who received the lowest dose. Subsequent enrollment was determined by decreasing age and increasing dose. Complete studies were performed on 63 patients. No age- or dose-dependent effects on pharmacokinetic parameter estimates were noted. Mean pharmacokinetic parameter estimates were as follows: half-life, 1.13 +/- 0.15 h; volume of distribution at steady state, 0.43 +/- 0.06 liters/kg; mean residence time, 1.57 +/- 0.11 h; clearance, 5.63 +/- 0.75 ml/min/kg; and renal clearance, 2.53 +/- 0.50 ml/min/liters kg. Approximately 55% of the administered dose was recovered as unchanged drug in the urine during the 12 h after dosing. No significant side effects were reported in any patients. By using the derived pharmacokinetic parameter estimates, a dose of 20 mg/kg given every 8 h will maintain plasma meropenem concentrations above the MIC that inhibits 90% of strains tested for virtually all potentially susceptible bacterial pathogens.

Aging↗
PubMed1995

A gene cluster involved in the utilization of both free heme and heme:hemopexin by Haemophilus influenzae type b.

The utilization of heme bound to the serum glycoprotein hemopexin by Haemophilus influenzae type b (Hib) strain DL42 requires the presence of the 100-kDa heme:hemopexin-binding protein encoded by the hxuA gene (M. S. Hanson, S. E. Pelzel, J. Latimer, U. Muller-Eberhard, and E. J. Hansen, Proc. Natl. Acad. Sci. USA 89:1973-1977, 1992). Nucleotide sequence analysis of a 5-kb region immediately upstream from the hxuA gene revealed the presence of two genes, designated hxuC and hxuB, which encoded outer membrane proteins. The 78-kDa HxuC protein had similarity to TonB-dependent outer membrane proteins of other organisms, whereas the 60-kDa HxuB molecule most closely resembled the ShlB protein of Serratia marcescens. A set of three isogenic Hib mutants with cat cartridges inserted individually into their hxuA, hxuB, and hxuC genes was constructed. None of these mutants could utilize heme:hemopexin. The hxuC mutant was also unable to utilize low levels of free heme, whereas both the hxuA and hxuB mutants could utilize free heme. When the wild-type hxuC gene was present in trans, the hxuC mutant regained its ability to utilize low levels of free heme but still could not utilize heme:hemopexin. The hxuA mutant could utilize heme:hemopexin when a functional hxuA gene from a nontypeable H. influenzae strain was present in trans. Complementation analysis using this cloned nontypeable H. influenzae hxuA gene also indicated that the HxuB protein likely functions in the release of soluble HxuA from the Hib cell. These studies indicate that at least two and possible three gene products are required for utilization of heme bound to hemopexin by Hib strain DL42.

Amino Acid Sequence↗
PubMed1994

Serologic response to standard inactivated influenza vaccine in human immunodeficiency virus-infected children.

We compared the serologic response of 46 human immunodeficiency virus (HIV)-infected children and adolescents and 61 age-matched controls to standard trivalent inactivated influenza vaccine (A/Taiwan (H1N1), A/Shanghai (H3N2), B/Yamagata). Children were immunized according to the package insert recommendations before the 1990 to 1991 influenza season. Serum antibody titers to influenza A were determined before and 1 month after each vaccination and compared for study and control subjects. Serologic responses of HIV-infected participants were correlated with absolute CD4 counts and stage of HIV disease. Regardless of age or HIV status, all groups responded with significant increases in antibody to the influenza A strains (range, 2.1-fold to 11.8-fold), with the exception that antibody to H3N2 rose only 1.5-fold (P = 0.058) among HIV-positive subjects > or = 9 years old. Pre- and postimmunization antibody titers were significantly higher for controls than for HIV-positive subjects. There was no correlation between serologic responses and CD4 counts among HIV-infected subjects, but those with Centers for Disease Control and Prevention-defined acquired immunodeficiency syndrome responded significantly less well to vaccine. We conclude that HIV-infected children and adolescents produce significant antibody rises after inactivated influenza A vaccination but that their absolute antibody concentrations are lower than those seen in age-matched controls.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Tuberculosis in infancy in the 1990s.

In 1990, 25,701 cases of tuberculosis (TB) were reported in the United States, the largest annual increase since 1953. Children younger than 15 years of age accounted for 1596 new cases. The resurgence of TB can largely be contributed to the HIV epidemic. The clinical course, diagnosis, therapy, and prevention of TB in the perinatal period and in infancy are discussed in view of the epidemics of HIV and TB in the adult population.

AIDS-Related Opportunistic Infections↗
PubMed1993

Antibiotic-induced bacterial killing stimulates tumor necrosis factor-alpha release in whole blood.

Rapid lysis of gram-negative bacteria is associated with considerable release of free endotoxin. Production of tumor necrosis factor (TNF) from adult whole blood ex vivo in response to bacterial products generated during antibiotic killing of Haemophilus influenzae type b (Hib) was investigated. Heparinized whole blood released TNF in a dose-dependent fashion in response to purified lipooligosaccharide of Hib. Bacteria (10(4)-10(7) cfu/mL) were placed into a Transwell filter insert (0.1 microns) and incubated with whole blood in the presence of various antibiotics. Exposure to ceftriaxone resulted in significantly greater release of TNF during killing of Hib than did exposure to imipenem, despite similar degrees of bacterial killing at 6 h. Polymyxin B inhibited the ceftriaxone-induced TNF release by 97%-99%, indicating that free endotoxin was the predominant stimulus for the increase in TNF release in this system. These observations suggest that ceftriaxone-induced killing of Hib results in bacterial cell wall products that are more proinflammatory than those produced by imipenem.

Adult↗
PubMed1993

Ventriculoperitoneal shunt infections with gram-negative bacteria.

Infection causes major morbidity and mortality in patients with cerebrospinal fluid (CSF) shunts. The prognosis of CSF shunt infections caused by Gram-negative bacteria (GNB) has been thought to be particularly poor. The authors reviewed all GNB shunt infections treated at Children's Memorial Hospital from January 1986 to January 1990 (n = 23). Of these infections 20 (87%) occurred within 4 weeks after shunt revision (median, 10 days). The most frequent symptoms were fever, lethargy, and irritability; the illness was not severe in the majority of these patients. Escherichia coli was isolated from 12 of 23 patients (52%), Klebsiella pneumoniae from 5 (22%), and mixed GNB from 3 (13%) patients. Initial treatment always included immediate shunt removal, externalized ventricular drainage, and intravenous antibiotics. Extraventricular drainage revision and/or intraventricular antibiotics were required in four patients whose CSF cultures were persistently positive for GNB. At admission, these patients had CSF glucose levels of < 10 mg/dl and CSF positive for GNB by Gram's stain. The overall cure rate was 100%, and no recurrence was observed; however, a subsequent infection with a different organism developed in four patients. Only 2 of 19 patients (11%) who were followed up suffered apparent CNS damage. One patient died of unrelated causes shortly after treatment. Our findings indicate that 1) patients with GNB CSF shunt infections often appear relatively well at presentation; 2) CSF positive for GNB by Gram's stain and very low CSF glucose levels predict continued positive CSF cultures, despite appropriate antibiotic therapy; and 3) GNB CSF shunt infections can be successfully treated by prompt shunt removal, extraventricular drainage, and intravenous antibiotics.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Bacterial Agents↗
PubMed1992

Lymphocyte subsets in healthy children during the first 5 years of life.

OBJECTIVE: To assess whether relative and absolute values of CD4 and CD8 lymphocytes and CD4/CD8 ratio change in relation to age, and to estimate the fifth and 95th percentiles for these values in children of various ages. PATIENTS AND METHODS: Phenotypic analysis of lymphocyte subsets was performed on blood samples from 208 healthy children, aged 1 through 59 months, using standard flow cytometric techniques. RESULTS: Regression analysis demonstrated that CD4 and CD8 lymphocyte counts declined significantly with advancing age (P less than .000001 and P = .03, respectively). Since CD4 and CD8 counts depend on total lymphocyte count, the percentage of total lymphocytes of each phenotype was also analyzed and demonstrated that the CD4 percentage was highly age dependent (P less than .000001). The CD8 percentage increased with age (P = .0001) but not as much as the CD4 percentage decreased. Median CD4 counts (fifth and 95th percentiles) for children 2 through 3, 4 through 8, 12 through 23, and 24 through 59 months of age were 2.83 (1.46 to 5.11), 2.95 (1.69 to 4.61), 2.07 (1.02 to 3.60), and 1.80 (0.90 to 2.86) x 10(9)/L, respectively. CONCLUSION: Healthy children's CD4 lymphocyte counts are considerably higher than previously established adult values. These data demonstrate that age is an important consideration in interpretation of lymphocyte subsets in children. This may be especially relevant in children who are infected with the human immunodeficiency virus, where CD4 lymphocyte values play a central role in monitoring disease progression and determining thresholds for medical interventions.

CD4-CD8 Ratio↗
PubMed1992

Bacterial and fungal colonization of endotracheal tubes in children: a prospective study.

OBJECTIVES: To evaluate both the frequency and route of endotracheal colonization of intubated children by pathogens and to assess the usefulness of Pediatric Risk of Mortality scoring and measurement of gastric pH in predicting this colonization. DESIGN: Prospective data collection. SETTING: A multidisciplinary pediatric ICU. PATIENTS: Nineteen children with medical/surgical problems who were intubated for at least 4 days. INTERVENTIONS: Buccal mucosa, and endotracheal and gastric aspirates were cultured for pathogens immediately after endotracheal intubation and daily for 4 to 5 days. Pediatric Risk of Mortality scores were calculated at the time of endotracheal intubation; gastric pH was measured each time that the cultures were obtained. MEASUREMENTS AND MAIN RESULTS: The buccal mucosae of ten (53%) of 19 children were colonized with Candida species at the time of endotracheal intubation. This colonization correlated with the degree of physiologic instability as measured by Pediatric Risk of Mortality scores (12.9 +/- 2.8 SEM for those patients colonized vs. 4.9 +/- 1.0 for those patients not colonized; p = .01), but not with preintubation antibiotic therapy. Eleven (58%) children acquired 27 endotracheal pathogens after the day of intubation. The buccal mucosa was the initial site of colonization of 19 (70%) of 27 of the acquired pathogens. A gastric pH of > 3.0 at the time of intubation correctly predicted colonization in nine of 11 children (p < .025, Fisher's exact test); a Pediatric Risk of Mortality score of > 8 at the time of endotracheal intubation correctly predicted colonization in eight of 11 patients (p < .05, Fisher's exact test). CONCLUSIONS: Colonization of the buccal mucosa appears to be the crucial antecedent to endotracheal colonization in children. In children, gastric pH and Pediatric Risk of Mortality scores at the time of endotracheal intubation can predict pathogenic endotracheal colonization within 4 days of intubation. Selective decontamination regimes may be appropriate for these patients, especially those regimes that are directed to the buccal mucosa.

Adolescent↗
PubMed1991

Clindamycin treatment of chronic pharyngeal carriage of group A streptococci.

We previously demonstrated that chronic pharyngeal carriage of group A beta-hemolytic streptococci (GABHS) can be terminated by intramuscular administration of benzathine penicillin plus 4 days of orally administered rifampin. Because an effective oral regimen would be desirable, we compared clindamycin with P + R for treating GABHS carriage. Healthy, symptom-free GABHS carriers were randomly assigned to receive orally administered clindamycin (20 mg/kg per day) three times a day for 10 days or intramuscularly administered benzathine penicillin with oral doses of rifampin (20 mg/kg per day) twice a day for 4 days. Compliance was documented by antibiotic activity in urine. Throat cultures for GABHS were obtained every 3 weeks for up to 9 weeks after treatment. Patients who had positive throat cultures for their original GABHS T type 3 weeks after randomization were crossed over to the other treatment. Treatment success was defined as eradication of the original GABHS T type, with all follow-up cultures negative. Clindamycin eradicated carriage in 24 (92%) of 26 patients; penicillin plus rifampin was effective in 12 (55%) of 22 patients (p less than 0.025). Including patients crossed over 3 weeks after enrollment, clindamycin was effective in 28 (85%) of 33 treatment courses compared with 12 of 22 courses of penicillin plus rifampin (p less than 0.05). We conclude that 10 days of oral clindamycin therapy was significantly more effective than benzathine penicillin plus 4 days of orally administered rifampin for treatment of symptom-free GABHS carriers.

Administration, Oral↗
PubMed1991

Use of third-generation cephalosporins. Hemophilus influenzae.

Meningitis constitutes the major infection associated with H. influenzae. Caution must be used when selecting antibiotic treatment based on MIC data, alone, because bacterial levels in the cerebrospinal fluid are higher than those in the blood, on which MICs are calculated. Certain third-generation cephalosporins are effective in producing maximum killing of H. influenzae in the CSF. This strong bactericidal activity may actually prove to be detrimental, however, by augmenting the inflammatory response, and thus contributing to the complications and the sequelae of meningitis. The addition of an agent to block the exaggerated response may be possible.

Animals↗
PubMed1991

Serum tumor necrosis factor alpha, interleukin 1-beta, p24 antigen concentrations and CD4+ cells at various stages of human immunodeficiency virus 1 infection in children.

We measured the serum concentrations of tumor necrosis factor (TNF-alpha), interleukin 1-beta (IL-1-beta), p24 antigen, CD4+/CD8+ cells and immunoglobulins in 35 children at various stages of human immunodeficiency virus infection. Serum TNF-alpha concentrations were significantly higher in children with lymphocytic interstitial pneumonitis and in children with mildly symptomatic illness than in asymptomatic children or children with acquired immunodeficiency syndrome. In addition serum IL-1 concentrations were significantly higher in patients with lymphocytic interstitial pneumonitis than in asymptomatic, mildly symptomatic, or acquired immunodeficiency syndrome patients. Children with lymphocytic interstitial pneumonitis had the highest serum TNF-alpha and IL-1 concentrations. Among symptomatic children serum TNF-alpha concentrations correlated positively with those of IL-1, and both were inversely related to the amount of p24 antigen. TNF-alpha values in excess of 50 pg/ml were observed more frequently among patients with CD4+ cell count greater than 400/mm3 than in those with CD4+ cell count less than 400/mm3. We did not find any association between elevated TNF-alpha concentrations and cachexia, opportunistic infections or progressive encephalopathy.

Acquired Immunodeficiency Syndrome↗