Allergy & Immunology Specialist, Pediatrician
38 years of experience
Video profile
Accepting new patients
Central LA
University Children's Medical Group
4650 W Sunset Blvd
Los Angeles, CA 90027
323-361-2501
Locations and availability (1)

Education ?

Medical School Score Rankings
UMDNJ (1972)
  • Currently 3 of 4 apples
Top 50%

Awards & Distinctions ?

Awards  
Castle Connolly America's Top Doctors® (2002 - 2008, 2010 - 2014)
Castle Connolly's Top Doctors™ (2012 - 2013)
Patients' Choice Award (2011)
Compassionate Doctor Recognition (2011)
Appointments
University of Southern California School of Medicine
Professor of Clinical Head, Division of Clinical
Associations
American Academy of Hiv Medicine
American Academy of Allergy Asthma and Immunology
American Board of Allergy and Immunology
Long Island Allergy and Asthma Society
American Board of Pediatrics

Affiliations ?

Dr. Church is affiliated with 3 hospitals.

Hospital Affilations

Score

Rankings

  • Hollywood Presbyterian Medical Center
    1300 N Vermont Ave, Los Angeles, CA 90027
    • Currently 3 of 4 crosses
    Top 50%
  • Children's Hospital of Los Angeles *
    4650 W Sunset Blvd, Los Angeles, CA 90027
    • Currently 1 of 4 crosses
  • John Muir Medical Center-Concord Campus
  • * This information was reported to Vitals by the doctor or doctor's office.

    Publications & Research

    Dr. Church has contributed to 96 publications.
    Title Prediction of Individual Brain Maturity Using Fmri.
    Date September 2010
    Journal Science (new York, N.y.)
    Excerpt

    Group functional connectivity magnetic resonance imaging (fcMRI) studies have documented reliable changes in human functional brain maturity over development. Here we show that support vector machine-based multivariate pattern analysis extracts sufficient information from fcMRI data to make accurate predictions about individuals' brain maturity across development. The use of only 5 minutes of resting-state fcMRI data from 238 scans of typically developing volunteers (ages 7 to 30 years) allowed prediction of individual brain maturity as a functional connectivity maturation index. The resultant functional maturation curve accounted for 55% of the sample variance and followed a nonlinear asymptotic growth curve shape. The greatest relative contribution to predicting individual brain maturity was made by the weakening of short-range functional connections between the adult brain's major functional networks.

    Title Survey of R.t.s with Doctorates: Barriers to Conducting Research.
    Date August 2010
    Journal Radiologic Technology
    Excerpt

    In today's health care environment, the need to attract and retain doctorate-holding radiologic science practitioners and provide them the tools and resources necessary to pursue professional research funding and publication cannot be underestimated. To date, however, there have been few studies on the possible barriers that interfere with both research and professional publishing among these highly educated individuals. A review of the literature reveals that the overall lack of research and professional publishing by radiologic science professionals holding doctorates can itself become a barrier in that low academic productivity is associated with a perceived lack of professionalism, lack of respect from external health professions and the lack of creation of new knowledge.

    Title Task Control Signals in Pediatric Tourette Syndrome Show Evidence of Immature and Anomalous Functional Activity.
    Date December 2009
    Journal Frontiers in Human Neuroscience
    Excerpt

    Tourette Syndrome (TS) is a pediatric movement disorder that may affect control signaling in the brain. Previous work has proposed a dual-networks architecture of control processing involving a task-maintenance network and an adaptive control network (Dosenbach et al., 2008). A prior resting-state functional connectivity MRI (rs-fcMRI) analysis in TS has revealed functional immaturity in both putative control networks, with "anomalous" correlations (i.e., correlations outside the typical developmental range) limited to the adaptive control network (Church et al., 2009). The present study used functional MRI (fMRI) to study brain activity related to adaptive control (by studying start-cues signals), and to task-maintenance (by studying signals sustained across a task set). Two hypotheses from the previous rs-fcMRI results were tested. First, adaptive control (i.e., start-cue) activity will be altered in TS, including activity inconsistent with typical development ("anomalous"). Second, group differences found in task-maintenance (i.e., sustained) activity will be consistent with functional immaturity in TS. We examined regions found through a direct comparison of adolescents with and without TS, as well as regions derived from a previous investigation that showed differences between unaffected children and adults. The TS group showed decreased start-cue signal magnitude in regions where start-cue activity is unchanged over typical development, consistent with anomalous adaptive control. The TS group also had higher magnitude sustained signals in frontal cortex regions that overlapped with regions showing differences over typical development, consistent with immature task-maintenance in TS. The results demonstrate task-related fMRI signal differences anticipated by the atypical functional connectivity found previously in adolescents with TS, strengthening the evidence for functional immaturity and anomalous signaling in control networks in adolescents with TS.

    Title Pharmacokinetics of a New 10% Intravenous Immunoglobulin in Patients Receiving Replacement Therapy for Primary Immunodeficiency.
    Date August 2009
    Journal European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences
    Excerpt

    Intravenous immunoglobulin (IVIg) is used in treating immunodeficiencies and autoimmune or inflammatory disorders. As manufacturing processes and storage can alter IgG molecules, pharmacokinetic assessments are important for new preparations. Thus, we studied pharmacokinetics of IgPro10, a new 10% liquid IVIg product stabilised with l-proline, in patients with common variable immunodeficiency (CVID) and X-linked agammaglobulinaemia (XLA). Patients received IgPro10 for >or=4 months (median dose of 444mg/kg, at 3- or 4-week intervals). Median total IgG serum concentrations increased from 10.2g/l pre-infusion to 23.2g/l at infusion end. Serum IgG concentrations decreased in a biphasic manner; median terminal half-life was 36.6 days. Median half-lives were 33.2 for IgG(1), 36.3 for IgG(2), 25.9 for IgG(3) and 36.4 days for IgG(4). Specific antibody concentrations (anti-CMV, anti-Hemophilus influenzae type B, anti-tetanus toxoid and anti-Streptococcus pneumoniae) decreased with median half-lives of 22.3-30.5 days. IgPro10 pharmacokinetics were similar in patients with CVID and XLA, although patients with CVID showed higher levels of anti-tetanus and anti-S. pneumoniae antibodies than patients with XLA, suggesting residual specific antibody production. IgPro10 pharmacokinetics fulfilled expectations for and were similar to intact IgG products. Administration of IgPro10 at 3- or 4-week intervals achieved sufficient plasma concentrations of total IgG, IgG subclasses and antibodies specific to important pathogens.

    Title Functional Brain Networks Develop from a "local to Distributed" Organization.
    Date June 2009
    Journal Plos Computational Biology
    Excerpt

    The mature human brain is organized into a collection of specialized functional networks that flexibly interact to support various cognitive functions. Studies of development often attempt to identify the organizing principles that guide the maturation of these functional networks. In this report, we combine resting state functional connectivity MRI (rs-fcMRI), graph analysis, community detection, and spring-embedding visualization techniques to analyze four separate networks defined in earlier studies. As we have previously reported, we find, across development, a trend toward 'segregation' (a general decrease in correlation strength) between regions close in anatomical space and 'integration' (an increased correlation strength) between selected regions distant in space. The generalization of these earlier trends across multiple networks suggests that this is a general developmental principle for changes in functional connectivity that would extend to large-scale graph theoretic analyses of large-scale brain networks. Communities in children are predominantly arranged by anatomical proximity, while communities in adults predominantly reflect functional relationships, as defined from adult fMRI studies. In sum, over development, the organization of multiple functional networks shifts from a local anatomical emphasis in children to a more "distributed" architecture in young adults. We argue that this "local to distributed" developmental characterization has important implications for understanding the development of neural systems underlying cognition. Further, graph metrics (e.g., clustering coefficients and average path lengths) are similar in child and adult graphs, with both showing "small-world"-like properties, while community detection by modularity optimization reveals stable communities within the graphs that are clearly different between young children and young adults. These observations suggest that early school age children and adults both have relatively efficient systems that may solve similar information processing problems in divergent ways.

    Title Safety and Efficacy of Privigen, a Novel 10% Liquid Immunoglobulin Preparation for Intravenous Use, in Patients with Primary Immunodeficiencies.
    Date June 2009
    Journal Journal of Clinical Immunology
    Excerpt

    The present study was designed to evaluate the efficacy and safety of a novel, 10% liquid formulation of intravenous immunoglobulin, stabilized with 250 mmol/L L-proline (Privigen), in patients with primary immunodeficiency disease.

    Title Control Networks in Paediatric Tourette Syndrome Show Immature and Anomalous Patterns of Functional Connectivity.
    Date March 2009
    Journal Brain : a Journal of Neurology
    Excerpt

    Tourette syndrome (TS) is a developmental disorder characterized by unwanted, repetitive behaviours that manifest as stereotyped movements and vocalizations called 'tics'. Operating under the hypothesis that the brain's control systems may be impaired in TS, we measured resting-state functional connectivity MRI (rs-fcMRI) between 39 previously defined putative control regions in 33 adolescents with TS. We were particularly interested in the effect of TS on two of the brain's task control networks-a fronto-parietal network likely involved in more rapid, adaptive online control, and a cingulo-opercular network apparently important for set-maintenance. To examine the relative maturity of connections in the Tourette subjects, functional connections that changed significantly over typical development were examined. Age curves were created for each functional connection charting correlation coefficients over age for 210 healthy people aged 7-31 years, and the TS group correlation coefficients were compared to these curves. Many of these connections were significantly less 'mature' than expected in the TS group. This immaturity was true not only for functional connections that grow stronger with age, but also for those that diminish in strength with age. To explore other differences between Tourette and typically developing subjects further, we performed a second analysis in which the TS group was directly compared to an age-matched, movement-matched group of typically developing, unaffected adolescents. A number of functional connections were found to differ between the two groups. For these identified connections, a large number of connectional differences were found where the TS group value was out of range compared to typical developmental age curves. These anomalous connections were primarily found in the fronto-parietal network, thought to be important for online adaptive control. These results suggest that in adolescents with TS, immature functional connectivity is widespread, with additional, more profound deviation of connectivity in regions related to adaptive online control.

    Title Association of Staphylococcal Superantigen-specific Immunoglobulin E with Mild and Moderate Atopic Dermatitis.
    Date November 2008
    Journal The Journal of Pediatrics
    Excerpt

    OBJECTIVE: To examine the frequency of allergic sensitization to staphylococcal superantigens in young children with mild to moderate atopic dermatitis (AD). STUDY DESIGN: AD severity was assessed with objective Scoring AD. Serum IgE to staphylococcal enterotoxin (SE) A, SEB, SEC, SED, and toxic shock syndrome toxin-1 were measured with ImmunoCAP. Comparisons between mild AD and moderate AD were performed by using logistic regressions. RESULTS: The prevalence of allergic sensitization to staphylococcal superantigens in patients with mild and moderate AD was 38% and 63%, respectively. Allergic sensitization to staphylococcal superantigens, particularly SEA and SED, was found to be associated with moderate AD, compared with mild AD. CONCLUSIONS: Our results suggest that allergic sensitization to staphylococcal superantigens is common even in young children with mild to moderate AD, and such sensitization may contribute to the disease severity of these patients.

    Title Improved Estimates of Upper-ocean Warming and Multi-decadal Sea-level Rise.
    Date July 2008
    Journal Nature
    Excerpt

    Changes in the climate system's energy budget are predominantly revealed in ocean temperatures and the associated thermal expansion contribution to sea-level rise. Climate models, however, do not reproduce the large decadal variability in globally averaged ocean heat content inferred from the sparse observational database, even when volcanic and other variable climate forcings are included. The sum of the observed contributions has also not adequately explained the overall multi-decadal rise. Here we report improved estimates of near-global ocean heat content and thermal expansion for the upper 300 m and 700 m of the ocean for 1950-2003, using statistical techniques that allow for sparse data coverage and applying recent corrections to reduce systematic biases in the most common ocean temperature observations. Our ocean warming and thermal expansion trends for 1961-2003 are about 50 per cent larger than earlier estimates but about 40 per cent smaller for 1993-2003, which is consistent with the recognition that previously estimated rates for the 1990s had a positive bias as a result of instrumental errors. On average, the decadal variability of the climate models with volcanic forcing now agrees approximately with the observations, but the modelled multi-decadal trends are smaller than observed. We add our observational estimate of upper-ocean thermal expansion to other contributions to sea-level rise and find that the sum of contributions from 1961 to 2003 is about 1.5 +/- 0.4 mm yr(-1), in good agreement with our updated estimate of near-global mean sea-level rise (using techniques established in earlier studies) of 1.6 +/- 0.2 mm yr(-1).

    Title Down-regulation of Atopic Dermatitis-associated Serum Chemokines by Wet-wrap Treatment: a Pilot Study.
    Date May 2008
    Journal Annals of Allergy, Asthma & Immunology : Official Publication of the American College of Allergy, Asthma, & Immunology
    Title The Maturing Architecture of the Brain's Default Network.
    Date April 2008
    Journal Proceedings of the National Academy of Sciences of the United States of America
    Excerpt

    In recent years, the brain's "default network," a set of regions characterized by decreased neural activity during goal-oriented tasks, has generated a significant amount of interest, as well as controversy. Much of the discussion has focused on the relationship of these regions to a "default mode" of brain function. In early studies, investigators suggested that, the brain's default mode supports "self-referential" or "introspective" mental activity. Subsequently, regions of the default network have been more specifically related to the "internal narrative," the "autobiographical self," "stimulus independent thought," "mentalizing," and most recently "self-projection." However, the extant literature on the function of the default network is limited to adults, i.e., after the system has reached maturity. We hypothesized that further insight into the network's functioning could be achieved by characterizing its development. In the current study, we used resting-state functional connectivity MRI (rs-fcMRI) to characterize the development of the brain's default network. We found that the default regions are only sparsely functionally connected at early school age (7-9 years old); over development, these regions integrate into a cohesive, interconnected network.

    Title Development of Distinct Control Networks Through Segregation and Integration.
    Date October 2007
    Journal Proceedings of the National Academy of Sciences of the United States of America
    Excerpt

    Human attentional control is unrivaled. We recently proposed that adults depend on distinct frontoparietal and cinguloopercular networks for adaptive online task control versus more stable set control, respectively. During development, both experience-dependent evoked activity and spontaneous waves of synchronized cortical activity are thought to support the formation and maintenance of neural networks. Such mechanisms may encourage tighter "integration" of some regions into networks over time while "segregating" other sets of regions into separate networks. Here we use resting state functional connectivity MRI, which measures correlations in spontaneous blood oxygenation level-dependent signal fluctuations between brain regions to compare previously identified control networks between children and adults. We find that development of the proposed adult control networks involves both segregation (i.e., decreased short-range connections) and integration (i.e., increased long-range connections) of the brain regions that comprise them. Delay/disruption in the developmental processes of segregation and integration may play a role in disorders of control, such as autism, attention deficit hyperactivity disorder, and Tourette's syndrome.

    Title Recent Climate Observations Compared to Projections.
    Date May 2007
    Journal Science (new York, N.y.)
    Excerpt

    We present recent observed climate trends for carbon dioxide concentration, global mean air temperature, and global sea level, and we compare these trends to previous model projections as summarized in the 2001 assessment report of the Intergovernmental Panel on Climate Change (IPCC). The IPCC scenarios and projections start in the year 1990, which is also the base year of the Kyoto protocol, in which almost all industrialized nations accepted a binding commitment to reduce their greenhouse gas emissions. The data available for the period since 1990 raise concerns that the climate system, in particular sea level, may be responding more quickly to climate change than our current generation of models indicates.

    Title Nonlinear Pharmacokinetics of High-dose Recombinant Fusion Protein Cd4-igg2 (pro 542) Observed in Hiv-1-infected Children.
    Date April 2007
    Journal The Journal of Allergy and Clinical Immunology
    Title Pectin Anaphylaxis and Possible Association with Cashew Allergy.
    Date January 2007
    Journal Annals of Allergy, Asthma & Immunology : Official Publication of the American College of Allergy, Asthma, & Immunology
    Excerpt

    BACKGROUND: Inhalation of pectin has been identified as a cause of occupational asthma. However, allergic reactions to orally ingested pectin have not been reported. OBJECTIVES: To describe a child with pectin-induced food anaphylaxis and to discuss its possible relationship to cashew allergy. METHODS: A 3 1/2-year-old boy developed anaphylaxis once after eating cashews and later after eating a pectin-containing fruit "smoothie." He also has a history of generalized pruritus after eating grapefruit. Skin tests or radioallergosorbent tests (RASTs) were performed to pectin and other suspected food allergens. RESULTS: The child had a positive skin prick test reaction to pectin and a high RAST reaction to cashew and pistachio. He had a low-level positive RAST reaction to grapefruit. Results of allergy tests for the other potential food allergens were negative. The pectin in the smoothie was confirmed to be of citrus origin. Review of previous case reports of pectin-induced occupational asthma revealed several patients with allergies to and cross-reactivity with cashew. CONCLUSIONS: Ingestion, not only inhalation, of pectin can cause hypersensitivity reactions. Cashew, and possibly pistachio, allergy may be associated with pectin allergy, and the possibility of pectin allergy should be considered in cashew- or pistachio-allergic patients who have unexplained allergic reactions.

    Title Case Report: Evidence for Transplacental Transfer of Maternally Administered Infliximab to the Newborn.
    Date January 2007
    Journal Clinical Gastroenterology and Hepatology : the Official Clinical Practice Journal of the American Gastroenterological Association
    Excerpt

    BACKGROUND & AIMS: Control of Crohn's disease (CD) is important for conception and sustaining a pregnancy to term. Small series of infliximab use during pregnancy have reported favorable fetal and maternal outcomes. As a result of heightened maternal concern triggered by recent labeling changes, infliximab levels were measured in the newborn of a mother treated with infliximab. METHODS: Serum and breast milk infliximab levels were measured by enzyme-linked immunosorbent assay. RESULTS: A 32-year-old woman with treatment-refractory CD continued infliximab therapy throughout pregnancy. Five infusions of infliximab, 10 mg/kg, the last one 2 weeks before delivery, successfully controlled her symptoms. Six weeks after delivery, the breast-fed infant's serum infliximab level was 39.5 microg/mL. Infliximab was not detected in the breast milk. Serial measurements revealed a continued slow decline of the infant's infliximab levels during the following 6 months, despite resumption of breast-feeding and subsequent retreatments of the mother with infliximab. CONCLUSIONS: Clinically significant infliximab levels were detected in the offspring. High infliximab levels in the serum of this infant are likely due to placental transfer, not breast-feeding. Similar to other maternally acquired antibodies, the half-life of infliximab appears prolonged in newborns. The true short-term and long-term implications of exposure to infliximab during the newborn period are unknown. Patients and physicians must be informed about in utero exposure to infliximab and potentially other therapeutic antibodies. The timing of infusions to minimize antibody transfer to the fetus might be an important strategic consideration when therapeutic antibodies are used in pregnancy.

    Title Denial of Insurance Authorization at a Subspecialty Office As a Cause of Missed Opportunities for Influenza Vaccination in Children with Asthma.
    Date October 2006
    Journal Archives of Pediatrics & Adolescent Medicine
    Title Efficacy, Safety and Tolerability of a New 10% Liquid Intravenous Immune Globulin [igiv 10%] in Patients with Primary Immunodeficiency.
    Date September 2006
    Journal Journal of Clinical Immunology
    Excerpt

    The present clinical study was designed to evaluate the efficacy, pharmacokinetics and safety of a new 10% liquid intravenous immune globulin in patients with primary immunodeficiency diseases. Sixty-one adults and children with primary immuno-deficiency diseases received doses of 300-600 mg/kg body weight every 21-28 days for 12 months. No validated acute serious bacterial infections were reported. The 95% confidence interval for the annualized rate of acute serious bacterial infections (primary endpoint) was 0-0.060. A total of four predefined validated other bacterial infections commonly occurring in primary immunodeficiency disease subjects were observed; none were serious, severe or resulted in hospitalization. The median elimination half-life of IgG was 35 days. Median total IgG trough levels varied from 9.6 to 11.2 g/L. Temporally associated adverse experiences were determined for 72 h after each infusion and the most common adverse experience was headache, which was associated with 6.9% of infusions. The study met the primary endpoint for efficacy and demonstrated excellent tolerability of the new 10% liquid intravenous imunoglobulin preparation.

    Title Susceptibility of Pediatric Hiv-1 Isolates to Recombinant Cd4-igg2 (pro 542) and Humanized Mab to the Chemokine Receptor Ccr5 (pro 140).
    Date September 2006
    Journal The Journal of Allergy and Clinical Immunology
    Title Mixed-up Nuts: Identification of Peanuts and Tree Nuts by Children.
    Date September 2006
    Journal Annals of Allergy, Asthma & Immunology : Official Publication of the American College of Allergy, Asthma, & Immunology
    Excerpt

    BACKGROUND: Peanuts and tree nuts frequently cause severe allergic reactions. Nut avoidance is the key treatment, and accurate identification of nuts is essential for successful avoidance. OBJECTIVES: To determine the age at which nut-allergic and nonallergic children can accurately identify various nuts and whether nut-allergic children can identify nuts they should avoid. METHODS: A "nut box" was constructed containing samples of 11 common nuts and pine nuts. Nut-allergic and nonallergic children were asked to identify the nuts, and their responses were compared and correlated by age. Nut-allergic children were asked to identify the nut(s) that they should not eat. RESULTS: One hundred children (37 allergic and 63 nonallergic) were enrolled. The mean number of nuts correctly identified was only 2.7 per child and increased with age, but there was large variation. Fifty-nine children identified 2 or fewer nuts. Peanuts in the shell were identified most often (89% of children), followed by peanuts out of the shell (52%). Other nuts were identified less commonly, ranging from 32% for pistachios to 0% for Brazil nuts. Nut-allergic children were not better able to correctly identify tree nuts and were less able in the case of peanuts. Of the nut-allergic children, 10 (27%) could not identify the peanut or tree nut to which they were allergic. CONCLUSIONS: In general, children, including those who are allergic to nuts, can identify few nuts. This lack of recognition could put them at increased risk for unintentional ingestion. As part of an overall educational plan, nut-allergic children should be taught not only to avoid but also to identify the nut to which they are allergic.

    Title Thymic Volume, T-cell Populations, and Parameters of Thymopoiesis in Adolescent and Adult Survivors of Hiv Infection Acquired in Infancy.
    Date July 2006
    Journal Aids (london, England)
    Excerpt

    OBJECTIVES: Antiretroviral therapy has significantly prolonged the lifespan of children who acquire HIV infection in infancy, but the impact of HIV on thymus-mediated maintenance of T lymphocytes has not been studied. To examine the long-term effects of HIV infection in childhood on thymopoiesis, thymic volume and parameters of thymic function from clinically stable adolescents and young adults with HIV infection acquired in infancy were compared with those from uninfected controls. METHODS: Thymic volume was determined using three-dimensional reconstruction and volumetric analysis of non-contrast enhanced computed tomography images of the upper chest. The degree of fat involution was assessed using a semiquantitive scoring system. CD4 and CD8 T cell populations and T cell receptor recombination excision circles (TREC) concentrations in peripheral blood lymphocytes were measured in all subjects. RESULTS: Twenty youths (aged 17.6 +/- 2.5 years) with HIV infection acquired perinatally (n = 18) or by neonatal transfusion (n = 2) were enrolled whose HIV plasma viral load had been undetectable for a median of 3.1 years, along with 18 seronegative healthy young adults (aged 20.6 +/- 1.3 years). HIV infected subjects and controls had indistinguishable CD4 T cell counts, thymus volumes (20.5 versus 15.8 cm), thymic index scores, and TREC values. Thymic volume correlated with the number and percentage of CD4 T lymphocytes in the control group and with the number of TREC in CD4 lymphocytes in the HIV infected group. CONCLUSIONS: Long term survivors of pediatric HIV infection appear to have retained or recovered thymic volume and thymic activity approximating uninfected youths.

    Title Safety and Immunogenicity of Live Varicella Virus Vaccine in Children with Human Immunodeficiency Virus Type 1.
    Date June 2006
    Journal The Pediatric Infectious Disease Journal
    Excerpt

    Live varicella virus vaccine was administered to 10 stable human immunodeficiency virus type 1 (HIV-1)-infected children. Subjects were monitored for adverse reactions, HIV-1 plasma levels, CD4 T cell counts and immune responses. The vaccine was well-tolerated. Varicella-zoster virus-specific lymphocyte proliferative responses were detected in all subjects by 4 weeks and in 9 of 10 subjects 1 year after vaccination.

    Title Selective Survival of Peripheral Blood Lymphocytes in Children with Hiv-1 Following Delivery of an Anti-hiv Gene to Bone Marrow Cd34(+) Cells.
    Date May 2006
    Journal Molecular Therapy : the Journal of the American Society of Gene Therapy
    Excerpt

    Two HIV-1-infected children on antiretroviral therapy were enrolled into a clinical study of retroviral-mediated transfer of a gene that inhibits replication of HIV-1, targeting bone marrow CD34+ hematopoietic stem/progenitor cells. Two retroviral vectors were used, one encoding a "humanized" dominant-negative REV protein (huM10) that is a potent inhibitor of HIV-1 replication and one encoding a nontranslated marker gene (FX) to serve as an internal control for the level of gene marking. Peripheral blood mononuclear cells (PBMC) containing the huM10 gene or FX gene were detected by quantitative PCR at frequencies of approximately 1/10,000 in both subjects for the first 1-3 months following re-infusion of the gene-transduced bone marrow, but then were at or below the limits of detection (<1/1,000,000) at most times over 2 years. In one patient, a reappearance of PBMC containing the huM10 gene, but not the FX gene, occurred concomitant with a rise in the HIV-1 viral load during a period of nonadherence to the antiretroviral regimen. Unique clones of gene-marked PBMC were detected by LAM-PCR during the time of elevated HIV-1 levels. These findings indicate that there was a selective survival advantage for PBMC containing the huM10 gene during the time of increased HIV-1 load.

    Title Trichosporon Pullulans As a Complication of Chronic Granulomatous Disease in a Patient Undergoing Immunosuppressive Therapy for Inflammatory Bowel Disease.
    Date March 2006
    Journal The Pediatric Infectious Disease Journal
    Excerpt

    We describe a patient with chronic granulomatous disease and receiving immunosuppressive therapy for refractory granulomatous colitis who developed fatal fulminant pneumonia, with Trichosporon pullulans isolated from multiple sites. This case highlights potential difficulties in treating chronic granulomatous disease colitis with high dose immunosuppressants and suggests that T. pullulans may represent an opportunistic organism with high morbidity and mortality in such patients.

    Title White Matter Lesions Are Prevalent but Differentially Related with Cognition in Aging and Early Alzheimer Disease.
    Date January 2006
    Journal Archives of Neurology
    Excerpt

    BACKGROUND: White matter lesions (WMLs) are prevalent in nondemented aging and in Alzheimer disease (AD). Their relationship with cognition in the earliest stages of AD is unknown. OBJECTIVE: To assess the relationship between WMLs and cognition in nondemented aging and in early-stage AD. DESIGN: Cross-sectional study. SETTING: Alzheimer Disease Research Center, St Louis, MO. PARTICIPANTS: Participants were nondemented (n = 88) or had very mild (n = 48) or mild (n = 20) AD. MAIN OUTCOME MEASURES: Regression coefficients for deep WMLs and periventricular WMLs (PVWMLs) as predictors of cognition, after controlling for age, educational achievement, brain atrophy, and infarctlike lesions. RESULTS: White matter lesions were present in nondemented aging and in early-stage AD, with no group differences in deep WML burden and a modest PVWML burden increase in the AD group. The prevalence of infarctlike lesions was equivalent between groups. Age and hypertension were related to deep WML burden and PVWML burden. Deep WML burden and PVWML burden were associated with reduced global cognition in AD but not in nondemented aging. A PVWML x AD status interaction for global cognition suggests that the relationship between PVWMLs and cognition is modified by AD. In AD, global cognitive reductions were related to impairments in visual memory, processing speed, and executive function. CONCLUSIONS: White matter lesions are prevalent in nondemented aging and in early-stage AD, and their presence influences cognitive impairment in the earliest stages of AD. Individuals with early-stage AD may be more vulnerable to the cognitive effect of WMLs than nondemented aging individuals with similar WML burden.

    Title Variable Presentation of Disseminated Nontuberculous Mycobacterial Infections in a Family with an Interferon-gamma Receptor Mutation.
    Date December 2005
    Journal Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America
    Excerpt

    A previously healthy 13-year-old child who had disseminated Mycobacterium avium infection is described. Further history revealed disseminated mycobacterial infections in the patient's father and uncle, starting at 9 years old and 1 year old, respectively. Autosomal dominant interferon- gamma receptor mutation was subsequently identified. Clinical variability among the affected members of the same family is consistent with previous reports suggesting substantial variability in the clinical course of this disorder.

    Title Significant Decadal-scale Impact of Volcanic Eruptions on Sea Level and Ocean Heat Content.
    Date November 2005
    Journal Nature
    Excerpt

    Ocean thermal expansion contributes significantly to sea-level variability and rise. However, observed decadal variability in ocean heat content and sea level has not been reproduced well in climate models. Aerosols injected into the stratosphere during volcanic eruptions scatter incoming solar radiation, and cause a rapid cooling of the atmosphere and a reduction in rainfall, as well as other changes in the climate system. Here we use observations of ocean heat content and a set of climate simulations to show that large volcanic eruptions result in rapid reductions in ocean heat content and global mean sea level. For the Mt Pinatubo eruption, we estimate a reduction in ocean heat content of about 3 x 10(22) J and a global sea-level fall of about 5 mm. Over the three years following such an eruption, we estimate a decrease in evaporation of up to 0.1 mm d(-1), comparable to observed changes in mean land precipitation. The recovery of sea level following the Mt Pinatubo eruption in 1991 explains about half of the difference between the long-term rate of sea-level rise of 1.8 mm yr(-1) (for 1950-2000), and the higher rate estimated for the more recent period where satellite altimeter data are available (1993-2000).

    Title Reduced Occupancy of the Deeply Bound 0d(5/2) Neutron State in 32ar.
    Date October 2004
    Journal Physical Review Letters
    Excerpt

    The 9Be(32Ar, 31Ar)X reaction, leading to the 5/2+ ground state of a nucleus at the proton drip line, has a cross section of 10.4(13) mb at a beam energy of 65.1 MeV/nucleon. This translates into a spectroscopic factor that is only 24(3)% of that predicted by the many-body shell-model theory. We introduce refinements to the eikonal reaction theory used to extract the spectroscopic factor to clarify that this very strong reduction represents an effect of nuclear structure. We suggest that it reflects correlation effects linked to the high neutron separation energy (22.0 MeV) for this state.

    Title Long Term Tolerability and Safety of Enfuvirtide for Human Immunodeficiency Virus 1-infected Children.
    Date September 2004
    Journal The Pediatric Infectious Disease Journal
    Excerpt

    BACKGROUND: Enfuvirtide, a peptide inhibitor of human immunodeficiency virus (HIV)-1-host cell membrane fusion, is the first of a new class of antiretroviral agents, the entry inhibitors. The safety and antiretroviral activity of enfuvirtide treatment of 24 weeks in HIV-1-infected children has been previously documented. Here we present the long term tolerability and safety of enfuvirtide. METHODS: Fourteen children, 4 to 12 years of age, with incompletely suppressed HIV-1 infection were evaluated. Enfuvirtide was administered twice daily by subcutaneous injection. After the first 24 weeks of enfuvirtide dosing, subjects were evaluated every 8 weeks up to 96 weeks of therapy. At each visit, each subject had a physical examination and an assessment for adverse events with particular attention to evaluation of injection site reactions. Laboratory studies obtained at each visit included hematology and blood chemistry values, plasma HIV-1 RNA concentrations and CD4+ T cell counts. RESULTS: Of 14 subjects, 6 completed at least 96 weeks of treatment. One child discontinued enfuvirtide after 22 days of treatment because of an aversion to injections, and 1 child electively discontinued after week 24 because of surgical complications unrelated to study drug. Four subjects discontinued study because of virologic failure, defined as an increase or persistence of plasma HIV-1 RNA 1.0 copies/mL above baseline, which occurred between >or =log10 weeks 40 and 63. Two children experienced grade 3 adverse events resulting in discontinuation of the study drug; 1 subject developed grade 3 thrombocytopenia and 1 developed grade 3 edema at weeks 65 and 77, respectively. Eleven of 14 children had local injection site reactions during the first 24 weeks of treatment, 4 of the 12 subjects who continued treatment beyond week 24 reported local reactions. Generally, these local reactions were 1- to 3-cm tender nodules that developed after the injections and lasted for 1-2 days. Twelve children developed new diagnoses during treatment with enfuvirtide. None was judged to be definitively related to the study drug. Thirty-six percent of children starting enfuvirtide had HIV-1 RNA levels > 1 log10 copies/mL below baseline levels at week 96. Children remaining on enfuvirtide for the entire 96 weeks had a median of 65 cells/mm and 9% increase in CD4+ T cells. CONCLUSIONS: Enfuvirtide was generally safe and, except for a high rate of injection site reactions, well-tolerated in HIV-1-infected children for as long as 96 weeks.

    Title Rapid Intravenous Desensitization to Antithymocyte Globulin in a Patient with Aplastic Anemia.
    Date February 2004
    Journal Transplantation
    Title Population Pharmacokinetics of Enfuvirtide in Pediatric Patients with Human Immunodeficiency Virus: Searching for Exposure-response Relationships.
    Date December 2003
    Journal Clinical Pharmacology and Therapeutics
    Excerpt

    OBJECTIVE: Our objective was to describe the population pharmacokinetics and pharmacodynamics of enfuvirtide acting on viral ribonucleic acid in children with human immunodeficiency virus 1. METHODS: A 1-compartment population pharmacokinetic model with first-order absorption and elimination was fit to subcutaneous and intravenous dose pharmacokinetic data from a 2-part study, as follows: an intensive-sample pharmacokinetic design (observed dose) (subcutaneous and intravenous, n = 12) followed by a sparse-sample design (unobserved dose) (subcutaneous, n = 15). The parameters of this model are clearance (CL), volume of distribution (V), absorption rate (k(a)), bioavailability (F), and both interindividual and residual variability. Plasma ribonucleic acid concentrations over time were used to build a population viral pharmacodynamics model with the following parameters: viral clearance (CL(v)), initial viral concentration (A(0)), duration (tau) and rate (R) of preinfected cell-based viral input after enfuvirtide was begun, and interindividual and residual variability. RESULTS: The mean population CL and V of enfuvirtide for a child with a mean body weight of 21.3 kg were 1.42 L/h and 5.67 L, respectively. Patient weight affected CL and V. Volume appeared to differ between intensive and sparse sampling occasions, and this difference also affected the residual error variance. Time after the beginning of therapy did not significantly affect any pharmacokinetic parameter, supporting the absence of metabolic induction and inhibition. Although trends were present, no statistically significant relationship was seen between any pharmacokinetic-based individual enfuvirtide exposure measure and any virologic response measure. CONCLUSIONS: Regarding pharmacokinetics and pharmacodynamics, no statistically significant correlation between exposure measures and viral clearance was observed.

    Title Assessment of Thymic Activity in Human Immunodeficiency Virus-negative and -positive Adolescents by Real-time Pcr Quantitation of T-cell Receptor Rearrangement Excision Circles.
    Date October 2003
    Journal Clinical and Diagnostic Laboratory Immunology
    Excerpt

    Circular DNA molecules known as T-cell receptor rearrangement excision circles (TREC) arise during T-cell development and are present in cells that have recently emigrated from the thymus. In cross-sectional studies, the number of peripheral blood lymphocytes bearing TREC decreases with age, consistent with an anatomically demonstrated loss of thymic epithelial tissue. TREC numbers increase following hematopoietic stem cell transplantation and during therapy for human immunodeficiency virus (HIV) infection. Quantitation of TREC has therefore been proposed as a parameter of thymic activity. In this study, we used real-time PCR to quantify TREC in peripheral blood samples obtained longitudinally from HIV-seronegative adolescents. TREC values in peripheral blood T cells were very stable throughout adolescence, once thought to be a time of rapid involution of the thymus. In addition, in a cross-sectional analysis, we examined TREC values in a cohort of HIV-positive adolescents and found evidence of ongoing thymopoiesis in perinatally infected individuals, despite lifelong infection. These data demonstrate the utility of TREC assessment in adolescents and that HIV infection does not uniformly result in accelerated thymic involution in childhood.

    Title New Direct Reaction: Two-proton Knockout from Neutron-rich Nuclei.
    Date August 2003
    Journal Physical Review Letters
    Excerpt

    The reaction 9Be(28Mg,26Ne+gamma)X has been studied at 82 MeV/nucleon together with two similar cases, 30Mg and 34Si. Strong evidence that the reactions are direct is offered by the parallel-momentum distributions of the reaction residues and by the inclusive cross sections. The pattern of the partial cross sections for 28Mg suggests the presence of correlations. A preliminary theoretical discussion based on eikonal reaction theory and the many-body shell model is presented. The reaction holds great promise for the study of neutron-rich nuclei.

    Title Progressive Outer Retinal Necrosis Caused by Varicella-zoster Virus in Children with Acquired Immunodeficiency Syndrome.
    Date June 2003
    Journal The Pediatric Infectious Disease Journal
    Title Safety and Antiretroviral Activity of Chronic Subcutaneous Administration of T-20 in Human Immunodeficiency Virus 1-infected Children.
    Date January 2003
    Journal The Pediatric Infectious Disease Journal
    Excerpt

    BACKGROUND: Entry inhibitors, a new class of antiretroviral agents, interfere with the attachment, coreceptor interaction or fusion of HIV-1 with host target cells. The fusion inhibitor T-20 is the first in this new class, and the present study is the first to examine chronic s.c. administration of T-20 to HIV-1-infected children. METHODS: Fourteen children, 4 to 12 years of age, with incompletely suppressed HIV-1 were studied. The median plasma viral load at baseline was 26,866 copies/ml (4.4 log10), and the median CD4 count was 523 cells/mm3. T-20 was administered twice daily by s.c. injection at 30 or 60 mg per m2 of body surface area per dose. For 7 days T-20 was added to the patients' background antiretroviral regimens; at Day 7 each subject's background therapy was changed to a regimen that was predicted to be virologically active, while T-20 was continued. Results are presented for the first 24 weeks of chronic T-20 dosing. RESULTS: T-20 was generally well-tolerated. One child discontinued the drug because of aversion to injections, but no child discontinued because of adverse events. Eleven (79%) of 14 children had local injection site reactions at some time during the chronic T-20 dosing. Eleven of 14 subjects achieved the protocol-specified milestone of at least a 0.7-log10 reduction in plasma HIV-1 RNA by Day 7. In 10 subjects (71%) virologic suppression of 1.0 log10 or greater was achieved at 24 weeks; 6 subjects (43%) had viral loads <400 copies/ml and 3 (21%) had fewer than 50 copies/ml at 24 weeks. CONCLUSIONS: These results indicate that a 24-week regimen of twice daily s.c. dosing of T-20 in HIV-1-infected children is safe and tolerable and that it is associated with suppression of HIV-1 replication during 24 weeks of administration.

    Title Short-term Complications of Central Line Placement in Children with the Human Immunodeficiency Virus.
    Date April 2002
    Journal Journal of Pediatric Surgery
    Excerpt

    PURPOSE: The aim of this study was to characterize the perioperative complications of central venous catheter placement in children infected with human immunodeficiency virus (HIV) METHODS: A retrospective chart review was conducted of all central venous catheters placed by the surgical service into HIV-infected children from 1988 to 1998 at a large urban children's hospital. Complications occurring within 1 month of catheter placement were analyzed for several host and environmental factors. RESULTS: Forty HIV-positive patients underwent 60 central venous access procedures. Thirty-two of the patients were severely immunosuppressed. Eight catheter placements (13%) resulted in perioperative complications, including hemorrhage (n = 2), site infection (n = 2), catheter sepsis (n = 2), thrombotic occlusion (n = 1), and a pleural effusion secondary to catheter malposition (n = 1). Only 3 patients required catheter removal. There was no significant relationship between either hemophilia or thrombocytopenia and perioperative hemorrhage. No significant relationship was found between infectious complications and preoperative white blood cell count, absolute neutrophil count, CD4% and CD4#, suggesting that a patient's compromised immune status should not be considered a contraindication to central venous catheter placement. CONCLUSION: The complication rate of central venous catheter placement into HIV-infected children is low (<15%), but is still higher than that of the general pediatric population. With careful preoperative preparation this procedure can be performed safely, even in patients with advanced HIV disease. J Pediatr Surg 36:1777-1780.

    Title Mitochondrial Dna Depletion, Near-fatal Metabolic Acidosis, and Liver Failure in an Hiv-infected Child Treated with Combination Antiretroviral Therapy.
    Date July 2001
    Journal The Journal of Pediatrics
    Excerpt

    A child with controlled human immunodeficiency virus infection presented with neurologic deterioration, lactic acidosis, and organic aciduria. Muscle biopsy revealed abnormal mitochondrial (mt) morphology, reduced mt enzyme activities, and mtDNA depletion. After adjustment of antiretroviral therapy to a regimen free of nucleoside analogs, marked improvement was seen in clinical status and mt abnormalities.

    Title Failure of Intravenous Immunoglobulin to Prevent Varicella-zoster Infection.
    Date June 2001
    Journal The Pediatric Infectious Disease Journal
    Title Determination of Dosing Guidelines for Stavudine (2',3'-didehydro-3'-deoxythymidine) in Children with Human Immunodeficiency Virus Infection.
    Date May 2001
    Journal Antimicrobial Agents and Chemotherapy
    Excerpt

    The results of the development of dosing guidelines for stavudine in human immunodeficiency virus (HIV)-infected children are summarized. Included in the integrated analyses were 21 and 33 HIV-infected pediatric and adult patients, respectively, from three phase I-II studies. Data for 21 children and 18 adults who received intravenous doses of 0.125 to 2 and 0.5 to 1 mg/kg of body weight, respectively, were used for the determination of dosing guidelines; exposure data for 16 children and 15 adults who received oral doses of 1 to 2 and 0.5 to 1 mg/kg/day, respectively, were used to validate the dosing recommendations for children. Significant relationships were observed between total body clearance (in milliliters per minute) in children and adults combined and demographic parameters of age, body weight, and body surface area (R(2) = 0.77 to 0.80; P = 0.0001). Models of approximated pediatric dose based on clearance values and direct adult exposure yielded a stavudine dosage of 2 mg/kg/day for children of < or =30 kg of body weight and 1 mg/kg/day (adult dose) for children of >30 kg of body weight.

    Title A Randomized, Double-blind Study of Triple Nucleoside Therapy of Abacavir, Lamivudine, and Zidovudine Versus Lamivudine and Zidovudine in Previously Treated Human Immunodeficiency Virus Type 1-infected Children. The Cnaa3006 Study Team.
    Date January 2001
    Journal Pediatrics
    Excerpt

    Abacavir (ABC) is a potent inhibitor of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase. We compared the efficacy, safety, and tolerability of combination therapy with ABC, lamivudine (3TC), and zidovudine (ZDV) versus 3TC and ZDV in antiretroviral experienced HIV-1-infected children over 48 weeks.

    Title Neonatal Urticaria As a Symptom of a Multisystem Inflammatory Disease.
    Date January 2001
    Journal The Journal of Allergy and Clinical Immunology
    Title Development of an Instrument to Assess Nutritional Risk Factors for Children Infected with Human Immunodeficiency Virus.
    Date March 2000
    Journal Journal of the American Dietetic Association
    Excerpt

    OBJECTIVE: To produce a simple and effective instrument to evaluate and monitor the nutritional risk of children infected with the human immunodeficiency virus (HIV). DESIGN: The test instrument was developed in consultation with 5 physicians, 5 nutritionists, and 5 social workers with expertise in caring for HIV-infected children. Patient information was collected through medical record review for 19 sociodemographic, 10 anthropometric, 4 biochemical, 6 dietary intake, and 19 medical factors. As a part of routine nutrition care, anthropometric data were obtained and the caregiver was asked to complete a 3-day diet record. Also recorded were the most recent CD4+ T-cell numbers and serum HIV p24 antigen and plasma HIV RNA levels. SUBJECTS/SETTING: Thirty-nine HIV-infected children were selected using quota sampling; that is, subjects were stratified by clinical class as defined by the Centers for Disease Control and Prevention. STATISTICAL ANALYSIS: The severity or degree of potential nutritional risk in each section (anthropometric, biochemical, dietary intake, and medical data) was graded (0 to 4, 0 = low risk) and summed. Reliability of internal consistency was determined through covariance matrixes. Validity was determined through Pearson product moment correlation coefficients to measure convergent and divergent validity; predictive validity was determined using analysis of variance. Correlation for validity was compared to 6 selected dependent variables: weight for height, weight growth velocity, lean body mass, serum albumin level, CD4+ T-cell numbers, and quantitative plasma HIV RNA levels. RESULTS: Of the 38 factors that were analyzed for reliability, 11 fell in the strongly reliable range: height for age, weight for age, clinical class, somatic protein stores, mid-arm circumference, weight for height, serum albumin, immunologic status, body mass index, energy intake, and opportunistic infection. CONCLUSIONS: Anthropometric, dietary intake, and medical data were reliable indicators of nutritional risk. The entire instrument was reliable after 8 of the weakest items were removed. The instrument was found to be valid and a good predictor of nutritional risk in HIV-infected children.

    Title Evaluation of the Effects of Oxandrolone on Malnourished Hiv-positive Pediatric Patients.
    Date December 1999
    Journal Pediatrics
    Excerpt

    OBJECTIVE: To determine the safety and efficacy of anabolic therapy to prevent or reverse wasting and malnutrition in human immunodeficiency virus (HIV)-infected pediatric patients. The anabolic steroid, oxandrolone, was evaluated because of its safe and effective use in other pediatric conditions. METHODS: Nine HIV-positive children who were malnourished or at risk for malnutrition (4 females, 5 males; 4-14 years of age) took oxandrolone for 3 months (.1 mg/kg/day orally). Quantitative HIV ribonucleic acid polymerase chain reaction and CD4(+) T-cell levels, complete blood cell count (CBC) and chemistry profile, endocrinologic studies, resting energy expenditure, respiratory quotient, nutritional measures, body composition assessment with quantitative computed tomography, and skinfold body composition measurements were determined before treatment, during treatment (3 months), and for 3 months after treatment. Statistical analyses were completed using the Friedman two-way analysis of variance and Spearman correlation tests. RESULTS: No adverse clinical or laboratory events or changes in Tanner staging or virilization occurred. Quantitative HIV ribonucleic acid polymerase chain reaction and CD4(+) T-cell levels did not change significantly. Insulin-like growth factor 1 increased, suggesting an anabolic effect of treatment. The rate of weight gain increased during treatment and was maintained after treatment. Linear growth continued and was maintained throughout treatment, whereas bone age did not increase significantly. Anthropometric assessments indicated an increase in muscle mass and a decrease in fat while patients were on treatment, and a mild decrease of muscle and increased fat posttreatment. Likewise, computed tomography scan results demonstrated similar changes in muscle mass. Resting energy expenditure and respiratory quotient remained stable throughout treatment and follow-up. No significant changes were seen in the quality of life questionnaire. CONCLUSIONS: Treatment with oxandrolone for 3 months in HIV-infected children was well-tolerated, safe, and associated with markers of anabolism. The latter effect was maintained partially for 3 months after discontinuation of a 3-month course of therapy. Additional studies are needed to assess the potential benefits and risks of a longer course of therapy or a higher dose of oxandrolone in HIV-infected children.

    Title Severe Combined Immunodeficiency: Otolaryngological Presentation and Management.
    Date May 1999
    Journal The Annals of Otology, Rhinology, and Laryngology
    Excerpt

    In order to increase the awareness of otolaryngologists of severe combined immunodeficiency syndrome (SCIDS) so they may contribute to an earlier diagnosis of this disorder, we performed a retrospective chart review of a multicenter series from 2 children's hospital medical centers. Eighteen cases were identified, and 14 had an otolaryngological presentation. The average age of presentation was 3.3 months, and 72% were males. Most cases were inherited in an X-linked fashion. Five patients had thrush; 4 had recurrent otitis media. Other otolaryngological presentations included cough, mouth ulcers, pharyngitis, mastoiditis, and bilateral neck abscess. The most severe form of immunodeficiency, SCIDS is a rare condition that involves a disorder in both T and B cell functions. The manifestations involving the head and neck include recurrent upper respiratory tract infections, otitis media, thrush, oral ulcers, and abscesses. It is important that SCIDS be considered in any infant with recurrences of these common infections.

    Title Ethical Issues of Placebo-controlled Trials.
    Date February 1999
    Journal The Journal of Pediatrics
    Title Serum and Cerebrospinal Fluid Pharmacokinetics of Intravenous and Oral Lamivudine in Human Immunodeficiency Virus-infected Children.
    Date February 1999
    Journal Antimicrobial Agents and Chemotherapy
    Excerpt

    We studied the pharmacokinetics of intravenously and orally administered lamivudine at six dose levels ranging from 0.5 to 10 mg/kg of body weight in 52 children with human immunodeficiency virus infection. A two-compartment model with first-order elimination from the central compartment was simultaneously fitted to the serum drug concentration-time data obtained after intravenous and oral administration. The maximal concentration at the end of the 1-h intravenous infusion and the area under the concentration-time curve after oral and intravenous administration increased proportionally with the dose. The mean clearance of lamivudine (+/- standard deviation) in the children was 0.53 +/- 0.19 liter/kg/h (229 +/- 77 ml/min/m2 of body surface area), and the mean half-lives at the distribution and elimination phases were 0.23 +/- 0.18 and 2.2 +/- 2.1 h, respectively. Clearance was age dependent when normalized to body weight but age independent when normalized to body surface area. Lamivudine was rapidly absorbed after oral administration, and 66% +/- 25% of the oral dose was absorbed. Serum lamivudine concentrations were maintained above 1 microM for >/=8 h of 24 h on the twice daily oral dosing schedule with doses of >/=2 mg/kg. The cerebrospinal fluid drug concentration measured 2 to 4 h after the dose was 12% (range, 0 to 46%) of the simultaneously measured serum drug concentration. A limited-sampling strategy was developed to estimate the area under the concentration-time curve for concentrations in serum at 2 and 6 h.

    Title Adenovirus Viremia in Human Immunodeficiency Virus-infected Children.
    Date July 1997
    Journal The Pediatric Infectious Disease Journal
    Title Acquired Protein S Deficiency in Children Infected with Human Immunodeficiency Virus.
    Date December 1996
    Journal The Pediatric Infectious Disease Journal
    Excerpt

    OBJECTIVES: To determine the prevalence of an acquired deficiency of protein S, a coagulation inhibitor, in children infected with the human immunodeficiency virus (HIV) and to identify clinical and laboratory features associated with this coagulation abnormality. METHODS: A convenience sample of HIV-infected children, ages 2 to 18 years, was evaluated for total, free and functional protein S; total and functional protein C; prothrombin and activated partial thromboplastin times; fibrinogen; antithrombin III activity; dilute Russell viper venom time; IgG anticardiolipin antibodies; von Willebrand factor antigen; C4b-binding protein; CD4+ T lymphocyte counts; HIV p24 antigen concentration; and serum beta 2-microglobulin concentrations. RESULTS: Thirty-four subjects were evaluated. Twenty-four subjects were infected perinatally and 10 by transfusion. Nine of the subjects were CDC Class N (asymptomatic), 13 were Class A/B (symptomatic without AIDS-defining condition) and 12 were Class C (AIDS). None had previously documented thrombosis, nephrosis or significant hepatic dysfunction. Twenty-six subjects (76.5%) had decreased free protein S, and 19 (55.9%) had functional protein S < 2 SD below the mean of laboratory controls. Decreased functional protein S was seen in 33.3% of Class N, 53.8% of Class A/B and 75.0% of Class C subjects. The prevalence of decreased total and functional protein S was greater in those with absolute CD4+ T lymphocyte counts < 200/mm3 compared to those with CD4+ counts > or = 200/mm3 (75.0% vs. 38.9%; chi square, 4.48, P = 0.034). A trend toward negative correlation was observed between protein S and duration of HIV infection only for Class N subjects. No linear correlation was seen between protein S and CD4+ T lymphocyte counts; and no significant relationships were observed between protein S values and CMV status, HIV p24 antigen, C4b-binding protein, von Willebrand factor antigen, IgG anti-cardiolipin antibodies or serum beta 2-microglobulin values. CONCLUSIONS: Acquired protein S deficiency is common in HIV-infected children. The high prevalence of this anticoagulant abnormality suggests an increased risk for thrombotic complications in this population.

    Title Systemic Gaseous Microemboli During Left Atrial Catheterization: a Common Occurrence?
    Date December 1995
    Journal Journal of Cardiothoracic and Vascular Anesthesia
    Excerpt

    Gaseous microemboli during cardiac surgery have been implicated as a potential cause of postoperative neurologic injury. Any monitoring technique that exposes the systemic circulation to atmospheric pressure could introduce gaseous microemboli, causing cerebral microembolization. The incidence of carotid artery gaseous microemboli was studied during left atrial catheter insertion.

    Title A Rapid and Sensitive Chemiluminescence Assay for Evaluation of Functional Opsonic Activity of Haemophilus Influenzae Type B-specific Antibodies.
    Date October 1995
    Journal Clinical and Diagnostic Laboratory Immunology
    Excerpt

    Luminol-enhanced chemiluminescence (CL) of heterologous neutrophils was used to assess the capacity of a 1-ng/ml concentration of Haemophilus influenzae type b (Hib)-specific antibodies to induce opsonization of Hib with autologous heat-inactivated sera from children immunized with Hib capsular polysaccharide-polyribosylribitolphosphate (Hib-PRP) conjugate vaccine. Serum samples from 15 of 36 children (42%) vaccinated with Hib-PRP conjugate vaccine had protective levels of Hib-specific antibodies of > or = 1,000 ng/ml. Ten of these 15 (67%) had poor or nonfunctional opsonic activity. Of the 10 children whose sera lacked opsonic activity, 5 (50%) presented with recurrent Hib infection. In contrast, none of the sera of 20 healthy adults lacked opsonic capability. CL intensity was proportional to the concentration of anti-Hib antibodies used for opsonization. Furthermore, the titers of Hib-PRP-specific antibody in children and adults did not correlate with opsonic activity. These results suggest that luminol-enhanced CL as described here with minute concentrations of antibody for opsonization can be used to assess functional capacity of anti-Hib antibodies after vaccination or natural infection in the evaluation of patients with recurrent infections.

    Title A Phase I/ii Evaluation of Stavudine (d4t) in Children with Human Immunodeficiency Virus Infection.
    Date September 1995
    Journal Pediatrics
    Excerpt

    OBJECTIVES. To determine the pharmacokinetic properties, tolerance, safety, and preliminary activity of stavudine in human immunodeficiency virus (HIV)-infected children. DESIGN. Phase I/II, open and dose-ranging (0.125 to 4 mg/kg/day in two divided doses). PATIENTS. Thirty-seven HIV-infected children (median age, 5.5 years; range, 7 months to 15 years) with a median CD4+ lymphocyte count at baseline of 242 cells/microL (range 2 to 2290 cells/microL). Thirty children had symptomatic HIV disease at entry; seven had HIV-related immunosuppression alone. Twenty-nine subjects had a history of prior zidovudine (ZDV) therapy. RESULTS. As compared with adults receiving the same weight-adjusted doses, the children we studied had lower maximum observed stavudine plasma concentrations (CMAX) and area under the plasma concentration versus time curves (AUC), and more rapid stavudine elimination. The absolute oral bioavailability of the drug ranged from 61% to 78%. There was no plasma accumulation of the drug between day 1 and week 12. Week 12 cerebrospinal fluid stavudine concentrations in seven subjects, obtained approximately 2 to 3 hours after oral doses, ranged from 16% to 97% of concomitant plasma concentrations. Stavudine was well-tolerated and there were no dose-related clinical or laboratory adverse events. One subject with baseline neurologic abnormalities experienced a transient episode of apparent pain or discomfort in her fingers, possibly related to stavudine. All other adverse events were attributed to underlying disease. Stavudine activity, measured indirectly by CD4+ lymphocyte count and serum p24 antigen concentration changes, was observed in some subjects. Progression of HIV disease and survival correlated with prior ZDV therapy, HIV disease classification, baseline CD4+ lymphocyte count, and weight growth velocity. CONCLUSIONS. Stavudine appears to hold promise for the treatment of HIV infection in children. Its pharmacokinetic properties are consistent and predictable, and it appears to be remarkably well-tolerated and safe. Although our study was not designed to assess the drug's efficacy, preliminary clinical and laboratory evidence of activity was observed.

    Title Sinusitis in Status Asthmaticus.
    Date April 1995
    Journal Clinical Pediatrics
    Excerpt

    The relationship between sinusitis and status asthmaticus (SA) remains obscure. The purposes of this study were to determine the prevalence of abnormal sinus radiographs (SXRs) and investigate possible risk factors among unselected children admitted with SA. Eighty-eight patients over 2 years of age (range 2 to 16 years) consecutively admitted with SA were studied. The principal investigator, blinded to SXR findings, interviewed and examined the patients with respect to 10 physical parameters and 14 historical parameters. Two staff radiologists, blinded to the clinical findings, interpreted the SXRs. Relationship of historical and physical findings with positive SXRs was determined by statistical analysis. Twenty-seven percent of patients were found to have abnormal SXRs, manifesting two thirds or greater opacification of the sinuses. The mean age, sex, and race of patients with abnormal SXRs was not significantly different from those with normal films. A history of two or more admissions per year for SA, and, in children under 5 years of age, a history of chronic otitis media, and the physical finding of otitis media were significantly more frequent among patients with abnormal SXRs. Although not found to be statistically significant, a history of sinusitis and cough occurred more frequently in association with abnormal SXRs.

    Title Pharmacokinetic Evaluation of the Combination of Zidovudine and Didanosine in Children with Human Immunodeficiency Virus Infection.
    Date July 1994
    Journal The Journal of Pediatrics
    Excerpt

    As part of a phase I/II trial in children infected with human immunodeficiency virus, we studied the pharmacokinetics of zidovudine and didanosine administered as single agents and in combination. Zidovudine (60 to 180 mg/m2 per dose) was given orally every 6 hours, and didanosine (60 to 180 mg/m2 per dose) every 12 hours. Pharmacokinetic samples were obtained from 54 patients and the area under the plasma concentration-time curve (AUC) was estimated by means of a previously defined limited sampling strategy. Follow-up blood samples were obtained after 4 and 12 weeks of treatment. The mean AUC for zidovudine ranged from 4.8 mumol.hr per liter at 60 mg/m2 to 11.0 mumol.hr per liter at the 180 mg/m2 level, and increased in proportion to the dose. The mean AUC for didanosine ranged from 2.8 mumol.hr per liter (60 mg/m2) to 8.0 mumol.hr per liter (180 mg/m2), with a wide interpatient variability. The AUCs of zidovudine and didanosine remained unchanged when the agents were administered in combination. There was no significant change in the AUCs of either drug after 4 and 12 weeks in comparison with those on day 3 of therapy. However, there was greater interpatient and intrapatient variability with didanosine than with zidovudine. These observations have implications for the future utility of therapeutic drug monitoring with these agents.

    Title Immunologic and Virologic Effects of Glucocorticoids on Human Immunodeficiency Virus Infection in Children: a Preliminary Study.
    Date June 1994
    Journal The Pediatric Infectious Disease Journal
    Excerpt

    The immune dysfunction in human immunodeficiency virus (HIV) infection is complex and cannot be explained solely on the basis of numerical depletion of T lymphocytes. Inappropriate, uncontrolled activation of the immune system may be involved. In a test of this hypothesis, five HIV-infected children were prospectively treated with prednisone and selected immunologic and virologic indices were analyzed. Subjects had marked T lymphopenia (CD4+ T lymphocytes < 500 cells/ml) and antigenemia (serum p24 antigen > 30 pg/ml) and were free of opportunistic infections. There was a significant drop in serum p24 antigen concentrations from baseline (60.2 +/- 10.1% SEM; P < 0.005) 4 weeks after initiation of prednisone, which returned to baseline concentrations as the prednisone was tapered. Concomitant with this decrease, there was decreased expression of cell surface activation markers (HLA-DR, CD25 (interleukin 2 receptor) and CD26 (Ta-1)) in peripheral T lymphocytes. There was no significant change in either T lymphocyte subset numbers or mitogen and antigen-specific lymphoproliferation. A regulatory dysfunction of the immune system, allowing inappropriate activation of T lymphocytes, may be involved in the pathogenesis of HIV disease, and further studies involving selective immunosuppression in HIV disease are warranted.

    Title Mycobacterium Avium Complex in Hiv-infected Children.
    Date January 1994
    Journal Annals of the New York Academy of Sciences
    Title Management of Asthma.
    Date December 1992
    Journal Pediatric Emergency Care
    Title Human Immunodeficiency Virus Infection in Children Who Received Transfusions in Mexico.
    Date June 1992
    Journal The Western Journal of Medicine
    Title An Inherited Defect of Neutrophil Motility and Microfilamentous Cytoskeleton Associated with Abnormalities in 47-kd and 89-kd Proteins.
    Date September 1991
    Journal Blood
    Excerpt

    A 2-month-old male Tongan infant presented with fever, severe skin and mucosal infections, hepatosplenomegaly, thrombocytopenia, and normal neutrophil counts. While polymorphonuclear neutrophil (PMN) morphology was normal, several neutrophil motile functions were found to be altered in the patient. Furthermore, two siblings had died in infancy with a similar clinical picture, raising the possibility of an inherited neutrophil defect. Random migration and chemotaxis, assessed by the under agarose method, were profoundly impaired. Actin polymerization, as measured by flow cytometry of N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)phallacidin (NBD-phallacidin)-stained PMNs, showed lower basal F-actin and a 1.75-fold increase in response to 10(-7) mol/L formyl-methionyl-leucyl-phenylalanine (FMLP) compared with a 4.51-fold increase in control. Microscopic examination of NBD-phallacidin-stained PMN spread on glass showed decreased area of spreading and F-actin-rich filamentous projections distinct from control. The early phase of FMLP-induced right angle light scattering was absent, similar to the effect caused by cytochalasin-B (CB), an inhibitor of actin polymerization. Accordingly, FMLP induced secretion of elastase without the addition of CB. Staphylococcus aureus killing was 50% of control whereas superoxide production response to FMLP and surface expression of CD11b were greater than twice normal. Partial defects in actin polymerization and scatter were seen in the parents and release of elastase, in the absence of CB, was also increased in both parents. Sodium dodecyl sulfate-polyacrylamide electrophoresis of whole cell proteins from the patient showed a marked decrease in an 89-Kd protein (8% of control) and a marked increase in a 47-Kd protein (4.2-fold). Both mother and father had decreased 89-Kd (77% and 42% of control) and increased 47-Kd proteins (2- and 3.4-fold), although neither had recurrent infections or chemotactic defects. These studies describe a new inherited actin dysfunction syndrome associated with severe propensity to fungal infection and draw attention to the proteins of apparent molecular weights of 89 Kd and 47 Kd, which may be of great importance in the regulation of actin polymerization in human PMNs.

    Title Underdiagnosis and Undertreatment of Chronic Sinusitis in Children.
    Date April 1991
    Journal Clinical Pediatrics
    Excerpt

    A review of outpatients diagnosed with sinusitis during the previous year by the allergy services of Childrens Hospital of Los Angeles and Kaiser Permanente, Orange County, revealed 34 patients who had protracted discomforting and debilitating symptoms. The mean duration of symptoms was approximately six months (range 1-14 months). None had been previously diagnosed as having sinusitis or received appropriate treatment. Although all were referred for evaluation of allergic rhinitis and/or asthma, approximately 1/3 were found to have neither of these conditions. Among patients who had asthma, their asthmatic symptoms were aggravated by the sinusitis. All patients eventually responded favorably to appropriate antibiotic therapy. Earlier diagnosis and appropriate therapy would have foreshortened the course of this very discomforting condition. In recent years, we have observed a marked increase in the number of patients referred with the chief complaint of "worsening allergy" and who were subsequently found to have sinusitis. Most of the patients experienced significant incapacitation for protracted periods before a correct diagnosis was made and treatment instituted. In all but a few cases, prompt and sustained improvement followed appropriate therapy. The purpose of this report is to present a retrospective review of 34 illustrative cases.

    Title Immune Functions in Children Treated with Biosynthetic Growth Hormone.
    Date October 1989
    Journal The Journal of Pediatrics
    Title Lymphomatoid Granulomatosis in a 13-month-old Infant.
    Date August 1989
    Journal The Journal of Rheumatology
    Excerpt

    Lymphomatoid granulomatosis is an infrequent, progressive, and frequently fatal vasculitis which typically occurs in middle aged males. We describe a 13-month-old infant with lymphomatoid granulomatosis who presented with chronic otitis media and "failure to thrive." Although it is well recognized that rheumatic conditions may result in failure to thrive, pediatricians often fail to consider this possibility and the proper diagnosis and treatment are correspondingly delayed. Lymphomatoid granulomatosis occurs with increased frequency in immunocompromised patients. In our case both hypogammaglobulinemia and persistent evidence of Epstein-Barr virus infection suggest that the infant was immunocompromised. Whether these factors predisposed this infant to lymphomatoid granulomatosis is uncertain. No patient with the onset of lymphomatoid granulomatosis prior to 7 years of age has been reported.

    Title Lack of Functional Asplenia in Hiv Infection.
    Date July 1989
    Journal Aids Research and Human Retroviruses
    Title Recurrent Fever and Abdominal Pain in a 4-year-old Boy.
    Date June 1989
    Journal Annals of Allergy
    Title Evaluation of a New, Shorter Method of Administration of Adrenergic Aerosols in the Treatment of Asthma.
    Date August 1988
    Journal Annals of Allergy
    Excerpt

    Approximately 15 to 20 minutes are usually required to administer adrenergic agents by nebulization in the treatment of asthma. But young children often do not tolerate these prolonged treatment periods. A "5-breath" method was found to provide comparable improvements in pulmonary function and result in minimal and comparable side effects, but required only one minute to administer. The "5-breath" method may, therefore, be the method of choice in the young or otherwise uncooperative patients.

    Title Cardiac Arrest Associated with Halothane Anesthesia in a Patient Receiving Theophylline.
    Date August 1988
    Journal Annals of Allergy
    Excerpt

    A case of a 10-year-old asthmatic patient who had cardiac arrest during induction for elective ear surgery is presented. The patient's serum theophylline level was 21.6 micrograms/mL one hour after surgery. It is likely that, since other factors that can contribute to cardiac arrest during the perioperative period were not present, the combined use of aminophylline and halothane was responsible.

    Title Okt4 Epitope Deficiency As a Cause of Reduced "helper" T Cells in Children at Risk for Human Immunodeficiency Virus Infection.
    Date August 1988
    Journal The Journal of Pediatrics
    Title Human Immunodeficiency Virus-associated Kaposi's Sarcoma in a Pediatric Renal Transplant Recipient.
    Date October 1987
    Journal Nephron
    Excerpt

    An 11-year-old boy developed Kaposi's sarcoma and progressive T lymphocyte deficiency 5 years after cadaveric kidney transplantation for end-stage renal disease. He had received 17 individual red blood cell transfusions prior to and during transplantation in 1980. Human immunodeficiency virus (HIV) was cultured from blood in cerebrospinal fluid and HIV antibodies were detected with enzyme immunoassay and immunoblot techniques. The recipient of the donor's other kidney was well and HIV antibody-negative. The patient was treated with etoposide with excellent although transient regression of tumor. Allograft function has remained stable despite minimal immunosuppressive therapy and the need for high-dose anticonvulsant therapy. This case represents the first pediatric patient with acquired immune deficiency syndrome (AIDS) and Kaposi's sarcoma following kidney transplantation.

    Title Severe Recurrent Pneumonia and Wheezing in a Young Infant.
    Date May 1987
    Journal Annals of Allergy
    Title Primary Candida Meningitis and Chronic Granulomatous Disease.
    Date June 1986
    Journal The American Journal of the Medical Sciences
    Excerpt

    The occurrence of two rare entities in a single patient can be fortuitous or may signify some deeper relationship. A young boy was recently treated for primary Candida meningitis. Autopsy findings suggested to an experienced pathologist the presence of chronic granulomatous disease (CGD), unrecognized during his life. The patient's identical twin brother was tested and found to have the typical laboratory features of CGD. The literature on Candida meningitis was reviewed and 15 cases were discovered that apparently arose in the absence of recognized predisposing causes. All but one of these cases occurred in males, and most occurred during the first three decades of life. The case reports and literature review presented herein suggest that CGD should be suspected when a case of "primary" Candida meningitis is encountered.

    Title New Scarlet Letter(s), Pediatric Aids.
    Date April 1986
    Journal Pediatrics
    Title Therapy of Acute Asthma: I. Evaluation of Successive Bronchodilator Treatments.
    Date October 1985
    Journal Annals of Allergy
    Excerpt

    Ninety-one children with acute asthma were studied to determine the extent of incremental improvement in pulmonary function afforded by successive doses of subcutaneous epinephrine, and by a bronchodilator aerosol in those patients refractory to epinephrine. A significant proportion of patients (69%), as expected, responded to the first injection. Among those who did not respond to the first injection a significant proportion (30%) responded to the second injection. Markedly fewer patients responded to subsequent bronchodilator treatments, including aerosols, if they did not improve significantly after the first two treatments. Patients with higher initial peak flow rates (PEFR) generally required fewer epinephrine injections, and achieved higher maximal PEFR than those with lower initial PEFR. Most asthmatic patients who required hospital admission had lower initial peak flow rates, were less responsive to epinephrine injections, and achieved lower maximal rates than those who could be discharged home.

    Title Transfusion-associated Acquired Immune Deficiency Syndrome in Infants.
    Date December 1984
    Journal The Journal of Pediatrics
    Excerpt

    Two preterm infant boys not known to be at risk developed clinical, laboratory, and pathologic features of acquired immune deficiency syndrome (AIDS) after receiving multiple blood transfusions in the neonatal period. Their clinical courses were characterized by failure to thrive, recurrent otitis media, hepatomegaly, and fatal interstitial pneumonia. Laboratory evaluation revealed progressive lymphopenia, reversed T helper/suppressor ratios, increased percentages of B-lymphocytes, decreased lymphoproliferative responses to mitogens, hyperimmunoglobulinemia, and high levels of circulating immune complexes. At postmortem examination thymic involution, lymphocyte depletion in spleen and lymph nodes, and micronodular mineralization in the central nervous system were seen. The findings were not specific for other known congenital immune deficiencies and were most indicative of AIDS. The lack of other risk factors suggests transmission of AIDS via blood transfusions in the neonatal period.

    Title Lymphocyte Subsets in Lymphoid Interstitial Pneumonitis.
    Date November 1984
    Journal Archives of Pathology & Laboratory Medicine
    Title Immune Functions in Methylmalonicaciduria.
    Date July 1984
    Journal Journal of Inherited Metabolic Disease
    Excerpt

    A variety of phagocytic cell and lymphocyte assays were employed to evaluate the immune status of four patients with methylmalonicaciduria . One patient had a depressed absolute granulocyte count and two patients had depressed neutrophil and monocyte chemotactic responses. All subjects had normal neutrophil phagocytic and bactericidal activities. One patient had a decreased T-cell number; blastogenic responses to phytohaemagglutinin and pokeweed mitogen were normal in all subjects. B lymphocyte measurements were variably abnormal; two children had decreased B-cell numbers; two had marginally decreased IgG levels; a third had an undetectable rubella titre; and two had elevated serum IgE concentrations. In vitro exposure of normal cells to methylmalonic acid concentrations up to 50 mg/100 ml did not affect chemotactic or lymphoproliferative responses. In conclusion, although B-cell function may be affected, no consistent abnormality of lymphocyte or phagocytic cell functions could be attributed to the metabolic disorder.

    Title Abnormal T-cell Subsets and Mitogen Responses in Hemophiliacs Exposed to Factor Concentrate.
    Date July 1984
    Journal American Journal of Diseases of Children (1960)
    Excerpt

    The acquired immune deficiency syndrome (AIDS) has been reported in hemophiliacs . We examined lymphocyte numbers and functions in 28 patients with hemophilia and 16 healthy adults. Healthy hemophiliacs who had received fewer than 150 commercial factor concentrate (CFC) infusions had normal T-cell numbers, T-cell subsets, and mitogen responses. Healthy hemophiliacs who had received more than 250 CFC infusions had a decreased number of Leu 3+ "helper" T cells, a decreased Leu 3-Leu 2 ratio, and decreased pokeweed mitogen responses. Hemophiliacs who had received greater than 250 CFC infusions and who had persistent lymphadenopathy had decreased Leu 3+ cells, increased Leu 2+ "suppressor" T cells, a decreased Leu 3-Leu 2 ratio, and decreased phytohemagglutinin responses. Abnormal results of T-cell studies were found in 67% of healthy hemophiliacs who had a high degree of CFC exposure and 100% of clinically abnormal hemophiliacs. These findings suggest that hemophiliacs are at risk for the development of the immunologic changes that characterize AIDS and that this risk is related to CFC exposure.

    Title Plasma Fibronectin Levels After Splenectomy and Splenic Autoimplantation in Rats with and Without Dietary Ascorbic Acid Supplementation.
    Date March 1984
    Journal Journal of Pediatric Surgery
    Excerpt

    The critical role of the spleen in protecting subjects from systemic bacterial infection is well known. Plasma fibronectin (PF), cold-insoluble globulin, and opsonic alpha2 surface binding glycoprotein, has regulatory influence on reticuloendothelial system clearance activity and it is important for maximal phagocytosis. Ascorbic acid (AA) also appears to play an important role in phagocytic cell function. The purposes of this study were to determine the effects of splenectomy and splenectomy with autoimplantation, with and without dietary AA supplementation, on PF levels. Six-week-old male Sprague-Dawley rats were divided into four experimental groups of 20 animals each: Nonoperated controls, sham-operated controls, totally splenectomized animals, and splenectomized animals with intraperitoneal autoimplantation. Each group was further randomly divided into two subgroups of 10 animals, those receiving dietary AA supplementation and those not receiving AA. PF levels were measured with a colorimetric assay immediately prior to and at 4 and 8 weeks after operation. Plasma AA determinations documented the effectiveness of dietary AA supplementation. PF levels in nonoperated and sham-operated controls increased significantly during the 8 weeks of experimentation. In contrast, PF levels decreased significantly following total splenectomy from 328 +/- 46 mcg/mL (mean +/- S.D.) to 285 +/- 46 at 4 weeks and rose to 303 +/- 77 at 8 weeks postoperatively in non-AA supplemented animals. Splenic autoimplantation eliminated this decrease in PF levels at 4 weeks. AA supplementation also protected against the decrease in PF levels in the splenectomized group. In the intragroup comparisons, AA supplementation did not produce a significant elevation of PF.(ABSTRACT TRUNCATED AT 250 WORDS)

    Title Induction of Tolerance to Factor Viii in a Child with a High-titer Inhibitor: in Vitro and in Vivo Observations.
    Date February 1984
    Journal The Journal of Pediatrics
    Excerpt

    High dose factor VIII concentrate was infused over 12 months in a 3-year-old child with hemophilia A and a high-titer inhibitor. This regimen was successful in producing clinical tolerance to the factor VIII and was associated with a fall of inhibitor titer from 85 BU to less than 1 BU. Subsequently, a rise in inhibitor to peak at 3.5 BU correlated with a decrease in infusion dose. In vitro studies using a microdroplet assay for immunoglobulin synthesis in the presence of varying concentrations of factor VIII was carried out prior to the clinical trial. This system indicated that the patient's peripheral blood mononuclear cells were stimulated to release IgG by 0.01 U/ml factor VIII coagulant activity and inhibited at 0.9 U/ml FVIIIc. Lymphocyte subsets were monitored during the course of therapy. The ratio of Leu-3a+/Leu-2a+ (helper/suppressor) varied considerably, fluctuating between a peak of 4.4 and low point of 0.6, with the initial pretrial ratio being 1.2.

    Title Antimuscle Antibody in Infantile Botulism.
    Date May 1983
    Journal The Western Journal of Medicine
    Title Isoetharine-isoproterenol: a Comparison of Effects in Childhood Status Asthmaticus.
    Date June 1982
    Journal Annals of Allergy
    Excerpt

    Eighteen children in status asthmaticus, six to 14 years of age, were systematically studied to compare the efficacy of aerosolized isoetharine and isoproterenol. The studies were conducted in a randomized, double-blind fashion. Five inhalations of 1% isoetharine and 0.5% isoproterenol were administered via a wall-mounted air/O2 nebulizing unit. Pulse, respiratory rate, blood pressure, FVC, PEFR, FEV1 and FEF25-75 were measured at the patient's bedside. Isoetharine produced significantly less cardiac side effect and tended to produce a greater improvement in pulmonary function than did isoproterenol. In addition, no change from baseline was noted in any of the parameters at 120 minutes following treatment with either medication.

    Title Antibody Responses After Splenectomy and Splenic Autoimplantation in Rats.
    Date December 1981
    Journal The Journal of Surgical Research
    Title Lymphoid Interstitial Pneumonitis and Hypogammaglobulinemia in Children.
    Date December 1981
    Journal The American Review of Respiratory Disease
    Excerpt

    Lymphoid interstitial pneumonitis is an uncommon process, and an association with hypogammaglobulinemia in children is rare. Three patients, a 10-yr-old boy (Patient 1), a 17-yr-old girl (Patient 2), and a 13-yr-old boy (Patient 3) were evaluated for progressive interstitial pneumonitis and hypogammaglobulinemia. At presentation, symptoms or signs of lung disease had been present for 9, 6, and 1.5 yr and consisted of severe exertional dyspnea asymptomatic pneumonitis on roentgenogram, and mild exertional dyspnea, respectively. Serum immunoglobulin deficiencies were variable with IgG and IgA being depressed in all patients and IgM being within normal limits in Patient 2. In vitro neutrophil function and T lymphocyte number and mitogen responses were normal. Measurement of in vitro immunoglobulin production suggested a primary B lymphocyte dysfunction. Pulmonary function testing revealed restrictive lung disease in Patient 1, arterial hypoxemia in Patients 1 and 2, and increased alveolar-arterial oxygen differences in all patients. Microscopic examination of lung specimens from each patient revealed diffuse lymphoid parenchymal infiltration with formation of follicles with occasional germinal centers, varying degrees of fibrosis, and negative examinations for viruses, bacteria, and fungi. The factors responsible for the cessation of antibody production and for the striking lympho-proliferative process seen in these patients remain to be identified.

    Title Circulating Immune Complexes in Patients with Cystic Fibrosis.
    Date November 1981
    Journal Chest
    Excerpt

    Circulating immune complexes (CICs) were measured in the sera of clinically stable and acutely infected patients with cystic fibrosis (CF). Twenty CF patients were studied when clinically stable; and additional 18 patients were studied during an acute exacerbation of pulmonary infection as evidenced by fever, tachypnea, increased white blood cell count, increased sputum production, and acute chest x-ray film changes. Three methods for determining CICs were employed: polyethyelene glycol precipitation, a C1q phase assay, and the Raji cell radioimmune assay. Ten of 20 clinically stable CF patients had one or two positive assays for CICs; two of 20 had two positive assays. In contrast, 16 of 18 acutely infected CF patients had a positive CIC test, and 12 of these were positive with two or three of the assays employed. Serum C3 and C4 concentrations and total hemolytic complement activity did not correlate with the presence of CICs in either patient group. These findings suggest that immune complex formation may mediate some of the tissue damage characteristic of CF, although this usually does not involve intravascular complement activation.

    Title A Self-help Program for Childhood Asthma in a Residential Treatment Center.
    Date August 1981
    Journal Clinical Pediatrics
    Excerpt

    A structured program designed to enhance self-treatment was successfully implemented in a residential center for asthmatic children. The ultimate objective of the program was to improve compliance with therapeutic regimens, which was felt to be a factor that had necessitated placement of many of the patients. The program was designed to educate the patient and the patient's family regarding the nature of asthma, its treatment and the importance of self-help. Efforts were also made to enhance the emotional maturity of the child. Patients remembered to take their medication over 90% of the time within 1 month of implementation of the program. a similar program was instituted for outpatient use.

    Title Neutrophil and Monocyte Chemotaxis in Acutely Infected Patients with Cystic Fibrosis.
    Date December 1980
    Journal Annals of Allergy
    Excerpt

    The purpose of this investigation was to determine if an acquired dysfunction of neutrophil or monocyte chemotaxis contributes to the susceptibility of cystic fibrosis patients to persistent infection. Leukocyte chemotaxis and the ability to generate chemotactic factors were measured in acutely infected cystic fibrosis patients and clinically well adult volunteers with an agarose technique. Chemotaxis of neutrophils and monocytes from cystic fibrosis patients were not found to differ from those of normal adult cells. Sera from test subjects produce chemotactic factors for normal neutrophils and monocytes.

    Title Abnormal Absorption of a Sustained-release Theophylline Preparation.
    Date October 1980
    Journal Annals of Allergy
    Title Normal Neutrophil and Monocyte Chemotaxis in Patients with Cystic Fibrosis.
    Date August 1979
    Journal The Journal of Pediatrics
    Title Steroid-dependent Asthma Treated with Inhaled Beclomethasone Dipropionate in Children.
    Date January 1979
    Journal Annals of Allergy
    Excerpt

    The efficacy of beclomethasone diproprionate aerosal (BDA) was studied in 27 steroid-dependent asthmatic children. In the double-blind portion of the study BDA was found to be superior to placebo. The benefits of BDA therapy were sustained through the two-year, open-label portion of the study. Adverse effects were few and minor. Transfer from oral corticosteroid therapy to BDA was carried out uneventfully and was not associated with untoward effects.

    Title Hyposmia Associated with Atopy.
    Date April 1978
    Journal Annals of Allergy
    Title Improvement of Idiopathic Nephrotic Syndrome Following Allergy Therapy.
    Date December 1977
    Journal Annals of Allergy
    Title Selective Food-specific Ige Antibodies in a Patient with Hyperimmunoglobulinemia E, Recurrent Infections and Severe Eczema.
    Date September 1977
    Journal Annals of Allergy
    Title A Modified Technique for the Radioallergosorbent Test.
    Date August 1976
    Journal Journal of Immunological Methods
    Excerpt

    A modification of the radioallergosorbent test (RAST) is described utilizing a multiple automated sample harvester. The technique increases the efficiency of the procedure by shortening the time required for its performance. A study is reported in which this method is compared to that recommended by the manufacturer.

    Title T Lymphocyte Dysfunction, Hyperimmunoglobulinemia E, Recurrent Bacterial Infections, and Defective Neutrophil Chemotaxis in a Negro Child.
    Date August 1976
    Journal The Journal of Pediatrics
    Title Serum Immunoglobulin E Concentrations and Radioallergosorbent Tests in Children with Atopic Dermatitis.
    Date March 1976
    Journal Pediatric Research
    Excerpt

    Serum IgE concentrations and the presence of allergen-specific IgE were determined in a series of 23 children with atopic dermatitis. In this group 83% had significantly elevated serum levels of IgE, 91% had coexistent respiratory allergy, 70% had radioallergosorbent test (RAST) evidence of pollen hypersensitivity, and 43% gave a history and demonstrated a RAST score consistent with milk or egg hypersensitivity. In patients with eczema a significant proportion of the elevated serum IgE appears to be antigen specific.

    Title The Effect of Miracil D Upon the Template Properties of Polynucleotides for a Bacterial Rna Polymerase.
    Date November 1972
    Journal Biochimica Et Biophysica Acta
    Title A Developmental Fmri Study of Reading and Repetition Reveals Changes in Phonological and Visual Mechanisms over Age.
    Date
    Journal Cerebral Cortex (new York, N.y. : 1991)
    Excerpt

    In this study of reading development, children (ages 7-10) and adults (ages 18-32) performed overt single-word reading and aural repetition tasks on high-frequency word stimuli during functional magnetic resonance imaging. Most regions showed similar activity across age groups. These widespread regions of similarity indicate that children and adults use largely overlapping mechanisms when processing high-frequency words. Significant task-related differences included greater activity in occipital cortex for the read task, and greater activity in temporal cortex for the repeat task; activity levels in these regions were similar for adults and children. However, age group differences were found in several posterior regions, including a set of regions implicated in adult reading: the left supramarginal gyrus, the left angular gyrus, and bilateral anterior extrastriate cortex. The angular and supramarginal gyrus regions, hypothesized to play a role in phonology, showed decreased activity in adults relative to children for high-frequency words. The extrastriate regions had significant activity for both the visual read task and auditory repeat task in children, but just for the read task in adults, showing significant task and age interactions. These results are consistent with decreasing reliance on phonological processing, and increasing tuning of visual mechanisms, with age.

    Title Parcellation in Left Lateral Parietal Cortex is Similar in Adults and Children.
    Date
    Journal Cerebral Cortex (new York, N.y. : 1991)
    Excerpt

    A key question in developmental neuroscience involves understanding how and when the cerebral cortex is partitioned into distinct functional areas. The present study used functional connectivity MRI mapping and graph theory to identify putative cortical areas and generate a parcellation scheme of left lateral parietal cortex (LLPC) in 7 to 10-year-old children and adults. Results indicated that a majority of putative LLPC areas could be matched across groups (mean distance between matched areas across age: 3.15 mm). Furthermore, the boundaries of children's putative LLPC areas respected the boundaries generated from the adults' parcellation scheme for a majority of children's areas (13/15). Consistent with prior research, matched LLPC areas showed age-related differences in functional connectivity strength with other brain regions. These results suggest that LLPC cortical parcellation and functional connectivity mature along different developmental trajectories, with adult-like boundaries between LLPC areas established in school-age children prior to adult-like functional connectivity.


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