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Biomedical subjects

R P Nelson

Publications and source records attributed to R P Nelson.

At least 37 records · Page 2Linked to original sources
PubMed1998

A phase I/II study of the protease inhibitor ritonavir in children with human immunodeficiency virus infection.

BACKGROUND: Ritonavir, a potent antiretroviral protease inhibitor, has been approved for the treatment of adults and children with human immunodeficiency virus (HIV) infection. In a phase I/II study, we assessed the safety, tolerability, and pharmacokinetic profile of the oral solution of ritonavir in HIV-infected children and studied the preliminary antiviral and clinical effects. METHODS: HIV-infected children between 6 months and 18 years of age were eligible. Four dose levels of ritonavir oral solution (250, 300, 350, and 400 mg/m given every 12 hours) were evaluated in two age groups (</=2 years, >2 years). Ritonavir was administered alone for the first 12 weeks and then in combination with zidovudine and/or didanosine. Clinical and laboratory parameters were monitored every 2 to 4 weeks. RESULTS: A total of 48 children (median age, 7.7 years; range, 0.5 to 14.4 years) were included in this analysis. Dose-related nausea, diarrhea, and abdominal pain were the most common toxicities and resulted in discontinuation of ritonavir in 7 children. Ritonavir was well absorbed at all dose levels, and plasma concentrations reached a peak 2 to 4 hours after a dose. CD4 cells counts increased by a median of 79 cells/mm3 after 4 weeks of monotherapy and were maintained throughout the study. Plasma HIV RNA decreased by 1 to 2 log10 copies/mL within 4 to 8 weeks of ritonavir monotherapy, and this level was sustained in patients enrolled at the highest dose level of 400 mg/m for the 24-week period. CONCLUSIONS: The oral solution of ritonavir has potent antiretroviral activity as a single agent and is relatively well tolerated by children when administered alone or in combination with zidovudine or didanosine.

Administration, Oral↗
PubMed1998

A phase I/II study of the protease inhibitor indinavir in children with HIV infection.

BACKGROUND: Indinavir, an inhibitor of the human immunodeficiency virus type 1 (HIV-1) protease, is approved for the treatment of HIV infection in adults when antiretroviral therapy is indicated. We evaluated the safety and pharmacokinetic profile of the indinavir free-base liquid suspension and the sulfate salt dry-filled capsules in HIV-infected children, and studied its preliminary antiviral and clinical activity in this patient population. In addition, we evaluated the pharmacokinetic profile of a jet-milled suspension after a single dose. METHODS: Previously untreated children or patients with progressive HIV disease despite antiretroviral therapy or with treatment-associated toxicity were eligible for this phase I/II study. Three dose levels (250 mg/m2, 350 mg/m2, and 500 mg/m2 per dose given orally every 8 h) were evaluated in 2 age groups (<12 years and >/=12 years). Indinavir was initially administered as monotherapy and then in combination with zidovudine and lamivudine after 16 weeks. RESULTS: Fifty-four HIV-infected children (ages 3.1 to 18.9 years) were enrolled. The indinavir free-base suspension was less bioavailable than the dry-filled capsule formulation, and therapy was changed to capsules in all children. Hematuria was the most common side effect, occurring in 7 (13%) children, and associated with nephrolithiasis in 1 patient. The combination of indinavir, lamivudine, and zidovudine was well tolerated. The median CD4 cell count increased after 2 weeks of indinavir monotherapy by 64 cells/mm3, and this was sustained at all dose levels. Plasma ribonucleic acid levels decreased rapidly in a dose-dependent way, but increased toward baseline after a few weeks of indinavir monotherapy. CONCLUSIONS: Indinavir dry-filled capsules are relatively well tolerated by children with HIV infection, although hematuria occurs at higher doses. Future studies need to evaluate the efficacy of indinavir when combined de novo with zidovudine and lamivudine.

Adolescent↗
PubMed1997

Multicenter crossover comparison of the safety and efficacy of Intraglobin-F with Gamimune-N, Sandoglobulin, and Gammagard in patients with primary immunodeficiency diseases.

The safety and clinical efficacy of a liquid, beta-propiolactone-stabilized intravenous gamma-globulin, Intraglobin-F, was evaluated in a multicenter, double-blind study comparing Intraglobin-F to Gamimune-N, Sandoglobulin, or Gammagard. beta-Propiolactone stabilizes the IgG molecule to decrease aggregate formation and is a potent virucidal agent that reduces the risk of viral transmission by intravenous gamma-globulin (IVIG) preparations. Twenty-seven patients with primary immunodeficiency diseases were enrolled at three centers. Each patient received 6 months of therapy with either Intraglobin-F or the IVIG preparation that they had received during the preceding 3 months, then crossed over to the other preparation. Twenty-three patients completed the study. One patient withdrew because of an adverse event, generalized urticaria. A second patient withdrew because of fatigue and perceived decreased efficacy. Adverse reactions were comparable and occurred in 8.7% of the infusions of Intraglobin-F and 6% of the infusions with Sandoglobulin. None were severe or life-threatening. There was no discernible difference in efficacy between any of the products. The number of days when patients noted symptoms in their diaries was similar for Intraglobin-F and the comparison preparations, 4158 vs 4143. Similarly, there were no differences in the number of physician visits (33 vs 22), days missed from work or school (405 vs 404), days with fever (41 vs 47), or days of prophylactic antibiotics (675 vs 642). There was an increase in the number of days when antibiotics were given therapeutically (578 vs 451); most of the difference was attributable to one patient. There also was a difference in the number of days of hospitalization (21 vs 0), but 19 of the days were accounted for by two patients. When the patients were asked to score their feeling of well-being on a scale of 1 to 5, with 1 being entirely well, the mean score for the patients on Intraglobin-F was 1.86 (range, 1.0 to 3.0), compared to 1.85 (range, 1.0 to 3.2) for patients while on the comparison preparations. Trough IgG levels were slightly lower during the period when patients were treated with Intraglobin-F compared to the other products. There were no abnormalities in blood chemistries or hematologic parameters. Thus, Intraglobin-F is comparable to three of the marketed IVIG preparations in efficacy and safety, as well as patient acceptability, and offers the additional benefit of an extra virucidal step to reduce further the risk of transmitting viral infections.

Adolescent↗
PubMed1997

Vertical transmission of human immunodeficiency virus type 1: seroreactivity by maternal antibodies to the carboxy region of the gp41 envelope glycoprotein.

Maternal antibodies against the envelope glycoprotein of human immunodeficiency virus type 1 (HIV-1) have previously been suggested to be important in influencing the rate of vertical transmission. In this study, serum antibody responses in mothers who did or did not transmit HIV-1 infection to their children were measured against the carboxy region of the transmembrane envelope glycoprotein gp41. Results indicate significantly higher binding reactivity of nontransmitter mothers compared with transmitters to three peptides spanning amino acids 771-810 and 841-856. In addition, high neutralization titers in maternal sera against HIV-1(MN) were associated with a nontransmission status. This is the initial report demonstrating a correlation between maternal antibody binding to epitopes within the carboxy region of gp41 envelope glycoprotein and lack of vertical transmission. Immunodetection that identifies antibodies to these regions in gp41 could therefore be considered a strategy to assess the risk of vertical transmission of HIV-1.

Amino Acid Sequence↗
PubMed1996

Diagnosis of pediatric human immunodeficiency virus infection by means of a commercially available polymerase chain reaction gene amplification.

OBJECTIVE: To assess the sensitivity and specificity of polymerase chain reaction (PCR) in infants and children at risk for human immunodeficiency virus (HIV) infection. DESIGN: A prospective, blinded study of 286 HIV-seropositive infants and children. Infection was diagnosed by antibody detection after 18 months of age, two positive direct tests (p24 antigen and HIV culture), or the presence of an illness that defines the acquired immunodeficiency syndrome. SETTING: University of South Florida and All Children's Hospital, St Petersburg, inpatient and outpatient centers. PARTICIPANTS: Two hundred eighty-six infants and children seropositive for HIV who were examined between July 1988 and September 1992. MAIN OUTCOME MEASURES: Sensitivity, specificity, and predictive values of a commercially available PCR test. RESULTS: Five hundred sixty-seven PCR tests were performed on samples from 286 seropositive subjects followed up for a minimum of 16 months. Of the subjects, 105 were confirmed to be infected and 181 uninfected. Overall, 96 of 105 initial PCRs in infected subjects were positive (sensitivity, 91.4%; positive predictive value, 99%). If samples obtained during the first week of life are excluded, 95 to 100 samples were positive (sensitivity, 95%). Of 181 initial PCR tests from seropositive subjects who seroreverted, 180 were negative (specificity, 99.4%,; negative predictive value, 95.2%). The predictive value of a positive test was 90.9% and that of a negative test was 93.1% in the first month of life. All 145 initial samples obtained between 5 weeks and 12 months of age correctly predicted infection status (positive predictive value, 100%). CONCLUSIONS: Gene amplification by means of a commercially available PCR is useful in the diagnosis of HIV infection for infants born to seropositive mothers. Between day 7 through 1 year of age, HIV infection is accurately diagnosed by the PCR assay.

Age Factors↗
PubMed1996

Allergen-specific IgE levels and mite allergen exposure in children with acute asthma first seen in an emergency department and in nonasthmatic control subjects.

BACKGROUND: Sensitization to allergens has been shown to be a risk factor for adults with acute asthma first seen in the emergency department. OBJECTIVE: The purpose of this study was to evaluate the prevalence of specific IgE to common aeroallergens in children with asthma first seen in the emergency department and in control subjects. METHODS: Fifty-four children, aged 3 to 16 years (mean age, 8.34 years) who visited the emergency department for treatment of acute bronchospasm or other illness, were evaluated. Specific IgE to seven common aeroallergens and four common storage mites was determined. Group I consisted of 29 patients who had acute bronchospasm and histories of recurrent asthma. Group II consisted of 25 control subjects who had no clinical history of atopic disease. Group I and II were compared for differences in the prevalence of positive RAST responses to the 11 allergens tested. Dust samples were collected from 17 homes of subjects in group I and from 13 homes of subjects in group II and were analyzed for levels of Der p 1 and Der f 1. RESULTS: Statistically significant differences in the prevalence of positive RAST results between groups I and II were found in response to: Dermatophagoides pteronyssinus, 89.6% versus 36% (p = 0.0001); Blattella germanica, 45.8% versus 9.5% (p = 0.018); Alternaria tenuis, 44.8% versus 4% (p = 0.001); and the storage mites Aleuroglyphus ovatus, 39.2% versus 4% (p = 0.002); Blomia tropicalis, 42.8% versus 0% (p = 0.0002); Chortoglyphus arcuatus, 46.4% versus 0% (p = 0.0001); and Lepidoglyphus destructor, 32.1% versus 0% (p = 0.0019). Mean specific IgE levels, expressed as percent of the total counts bound, were significantly higher in group I compared with group II only in response to D. pteronyssinus, 21.9% versus 2.1% (mean percent of total counts bound) (p = 0.0001). Analysis of dust samples revealed no significant differences between the two groups, except for a higher concentration of Der f 1 in the sofas of subjects in group II. CONCLUSION: Sensitization to D. pteronyssinus, storage mites, and, to a lesser extent, to A. tenuis and B. germanica is associated with acute childhood asthma that requires emergency treatment in Florida.

Acute Disease↗
PubMed1996

Serum total and specific IgE levels in children infected with human immunodeficiency virus.

BACKGROUND: Human immunodeficiency virus (HIV) infection is associated with polyclonal B-cell activation, and elevated IgE levels are found in infected adults. Chronic nasal symptoms, sinusitis, and otitis media are particularly common in children infected with HIV. The possible allergic cause of nasal symptoms in children infected with HIV has not been explored. OBJECTIVE: The study was designed to evaluate the relationship between HIV infection and IgE levels in a group of children infected with HIV. METHODS: Total serum IgE was measured by enzyme immunoassay and compared with values for age-matched normal subjects. Specific IgE was determined by RAST test to Dermatophagoides pteronyssinus, American cockroach, Bahia grass, short ragweed, cat, and oak. Lymphocyte subpopulations were determined by standard flow cytometry. RESULTS: Fifty-seven total IgE and 342 specific IgE levels were determined from 29 infected children (19 girls and 10 boys; ages, 7 to 150 months; mean age, 49 months). Initial IgE levels of 29 subjects ranged from 1.4 to 787.6 IU/ml (mean = 123.4 +/- 34.4 IU/ml). Nine of 29 (31%) subjects had initial IgE levels greater than two standard deviations higher than age-matched normal subjects. No patients had detectable specific IgE to any of the six aeroallergens. There was no correlation, as determined by linear regression analysis, between IgE levels and absolute CD4 number or CD4:CD8. CONCLUSION: Elevated total but not specific IgE is common in children infected with HIV and does not correlated with absolute CD4 lymphocyte count, suggesting that the elevated IgE level reflects a somewhat independent polyclonal activation of B-lymphocytes.

Adolescent↗
PubMed1995

Predominance of sterile immunoglobulin transcripts in a female phenotypically resembling Bruton's agammaglobulinemia.

The transcription pattern of the heavy chain immunoglobulin gene locus was analyzed in a 6-month-old female with agammaglobulinemia characterized by the absence of mature B cells in peripheral blood, arrested B cell development in the bone marrow and lack of germinal center development. DNA sequencing provided no evidence of mutations within the coding region of the Bruton's tyrosine kinase gene. Polymerase chain reaction-generated cDNA libraries from blood and bone marrow were screened initially using JH and CH oligodeoxynucleotide probes and VH family-specific probes. Only 10% of the transcripts constituted mature VDJC mu recombinations. Ninety percent of the cDNA were sterile immunoglobulin transcripts comprised of: DJC mu (DH-JHC mu), JC mu (JH-C mu), EC mu (enhancer spliced to C mu), SC mu and IC mu [corresponding to switch (S) and intron (I) regions spliced to C mu]. In the mature immunoglobulin transcripts, VH use indicated germline expression with little evidence of somatic mutation. All cDNA were of the C mu type. Different D segments, D-D joining events and unknown D-like elements were noted in the DJC mu and VDJC mu transcripts. This pattern of immunoglobulin rearrangements, along with the phenotypic cell surface antigen characteristics (CD19-), suggest that an earlier arrest in B cell development than is characteristic of Bruton's X-linked agammaglobulinemia has occurred in this patient.

Agammaglobulinaemia Tyrosine Kinase↗
PubMed1995

Maternal and child health and health care reform.

Women and children, because of particular characteristics and vulnerabilities, should be afforded special attention in health care reform. Health care reform provides an opportunity to positively affect the maternal and child health (MCH) status. Universal coverage of a comprehensive benefit package must be combined with a strong public health system of population-based services if benefits are to be realized. There must be an accountable public locus of responsibility for promoting MCH, including clear authority and resources for four primary activities: (1) core public health, (2) systems development, (3) coordinated services for children with special health care needs, and (4) access to care.

Adolescent↗
PubMed1994

Genomic organization and structure of Bruton agammaglobulinemia tyrosine kinase: localization of mutations associated with varied clinical presentations and course in X chromosome-linked agammaglobulinemia.

X chromosome-linked agammaglobulinemia is a life-threatening disease that involves a failure in normal development of B lymphocytes and is associated with missense mutations in BTK, a gene encoding a cytoplasmic tyrosine kinase (Bruton agammaglobulinemia tyrosine kinase, EC 2.7.1.112), a member of the Tec family of protein-tyrosine kinases. The genomic organization has been determined by using conventional restriction fragment mapping, extended DNA sequencing, and PCR fragment-sizing approaches. The DNA sequences of the 18 coding exons composing BTK and their flanking-region sequences are reported; an additional exon(s) encodes a 5' untranslated segment. Single-base-pair substitutions and 4-nt deletions resulted in amino acid replacement, premature termination, frameshift, and exon deletion in a group of X chromosome-linked agammaglobulinemia patients exhibiting different clinical presentations and courses. The nature of the mutations is interpreted in terms of the genomic organization of the BTK gene and the disease course in individual patients. Several examples are found in which the same mutation occurs in unrelated patients, and one of these mutations occurs at the same codon that is substituted in the murine form of BTK, resulting in X chromosome-linked immunodeficiency disease. Considerable variation in presentation and disease course in X chromosome-linked agammaglobulinemia appears associated with the nature and position of different missense mutations.

Agammaglobulinaemia Tyrosine Kinase↗
PubMed1994

Coronary risk factors in adolescents related to their knowledge of familial coronary heart disease and hypercholesterolemia: the Muscatine Study.

OBJECTIVE: To determine the utility of a school-based questionnaire, to identify adolescents with adverse coronary risk factor levels. DESIGN: In Muscatine, IA, students (9th through 12th grade) completed a questionnaire providing medical history information about first- and second-degree relatives. Anthropometric measures were obtained and blood pressure, lipid, lipoprotein, and apolipoprotein levels were determined. RESULTS: A history of parental coronary heart disease (CHD) was rare and a history of parental high cholesterol frequently was unknown; however, when known, a history of high cholesterol or early (30 to 55 years of age) or later (> 55 years of age) CHD (myocardial infarction, coronary bypass, or death from a heart attack) in grandfathers enriched the identification of adolescents with adverse coronary risk factors. Parental history of CHD was associated with an increased risk for high body mass index and low apolipoprotein A1 levels in their children. Grandfather history of early or later CHD was associated with an increased risk for low apolipoprotein A1 and high density lipoprotein cholesterol levels and high body mass index in their grandchildren. Students with positive grandfather histories of high cholesterol had higher total cholesterol, low density lipoprotein cholesterol, apolipoprotein B, and low density lipoprotein cholesterol to high density lipoprotein cholesterol ratios. Grandmother histories, because most were negative, did not help identify adolescents in this population with adverse coronary risk factors. CONCLUSIONS: A parental history of CHD as well as a grandfather history of high cholesterol or CHD enriches the identification of children with adverse coronary risk factor levels. The positive predictive values associated with using a school-based history obtained from adolescents, many with the aid of their parents, are small and many adolescents do not know their family history. It is essential that pediatricians inquire about parental and especially grandparental medical histories in accordance with the National Cholesterol Education Program guidelines to help identify children at highest familial risk. The importance of determining parental and grandparental histories of CHD or hypercholesterolemia should be emphasized to families who are uncertain of their histories to identify children and adolescents who require a physician's care. It is also important for pediatricians to remind their colleagues who care for patients with premature ischemic heart disease to refer their progeny for pediatric care so that their lipids and lipoproteins may be screened and counseling provided.

Adolescent↗
PubMed1993

Polycythemia as a complication of human immunodeficiency virus infection.

HIV infection is commonly associated with cytopenias. The occurrence of erythrocytosis is rare, with only one report in the medical literature. We have described the case of an asymptomatic patient found to be seropositive for HIV. The blood counts were initially normal except for mild eosinophilia and thrombocytopenia. Over the next 18 months erythrocytosis developed and thrombocytopenia worsened. Workup at that time revealed elevated red cell mass, suppressed erythropoietin, normal arterial oxygen saturation, and splenomegaly documented by abdominal computed tomography. Zidovudine therapy was started in April 1990, when the CD4 cell count dropped below 500/mm3. Over the next 4 months the hematologic indexes returned to normal levels. The patient remains asymptomatic.

Adult↗