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Biomedical subjects

Robert G Hamilton

Publications and source records attributed to Robert G Hamilton.

At least 19 recordsLinked to original sources
PubMed2006

Immunotherapy with a ragweed-toll-like receptor 9 agonist vaccine for allergic rhinitis.

BACKGROUND: Conjugating immunostimulatory sequences of DNA to specific allergens offers a new approach to allergen immunotherapy that reduces acute allergic responses. METHODS: We conducted a randomized, double-blind, placebo-controlled phase 2 trial of a vaccine consisting of Amb a 1, a ragweed-pollen antigen, conjugated to a phosphorothioate oligodeoxyribonucleotide immunostimulatory sequence of DNA (AIC) in 25 adults who were allergic to ragweed. Patients received six weekly injections of the AIC or placebo vaccine before the first ragweed season and were monitored during the next two ragweed seasons. RESULTS: There was no pattern of vaccine-associated systemic reactions or clinically significant laboratory abnormalities. AIC did not alter the primary end point, the vascular permeability response (measured by the albumin level in nasal-lavage fluid) to nasal provocation. During the first ragweed season, the AIC group had better peak-season rhinitis scores on the visual-analogue scale (P=0.006), peak-season daily nasal symptom diary scores (P=0.02), and midseason overall quality-of-life scores (P=0.05) than the placebo group. AIC induced a transient increase in Amb a 1-specific IgG antibody but suppressed the seasonal increase in Amb a 1-specific IgE antibody. A reduction in the number of interleukin-4-positive basophils in AIC-treated patients correlated with lower rhinitis visual-analogue scores (r=0.49, P=0.03). Clinical benefits of AIC were again observed in the subsequent ragweed season, with improvements over placebo in peak-season rhinitis visual-analogue scores (P=0.02) and peak-season daily nasal symptom diary scores (P=0.02). The seasonal specific IgE antibody response was again suppressed, with no significant change in IgE antibody titer during the ragweed season (P=0.19). CONCLUSIONS: In this pilot study, a 6-week regimen of the AIC vaccine appeared to offer long-term clinical efficacy in the treatment of ragweed allergic rhinitis. (ClinicalTrials.gov number, NCT00346086 [ClinicalTrials.gov] .).

Adult↗
PubMed2006

Long-term immunologic effects of broad-spectrum aeroallergen immunotherapy.

BACKGROUND: Limited data exist regarding extended, long-term immunologic effects of immunotherapy in polysensitized individuals. To study possible long-term effects, skin tests and specific IgE levels were obtained from subjects who had previously received broad-spectrum aeroallergen immunotherapy years before. METHODS: Eighty-two subjects (78% male, mean age 23 years) previously enrolled in a randomized, placebo-controlled trial of immunotherapy for treatment of childhood allergic asthma were reevaluated in adulthood (mean follow-up interval, 10.8 years) by puncture skin tests and CAP-RAST levels for major aeroallergens. All completed at least 18 months (median 27 months) of maintenance active treatment or placebo injections without subsequent immunotherapy. RESULTS: At adult follow-up, 36% of all skin tests to treatment allergens among subjects who received immunotherapy (n = 41) had significantly reduced intensity versus 26% of skin tests among placebo recipients (n = 41; p = 0.03). No significant differences were noted for individual treatment allergens. No significant differences were observed in the long-term changes of serum-specific IgE antibody levels for all treatment allergens between immunotherapy treatment and placebo groups (p = 0.43). The treatment and placebo groups had a similar acquisition of new skin test sensitivities from time of randomization in the original childhood trial to debriefing (15 vs. 20%; p = 0.28) and to adult follow-up (30 vs. 31%; p = 0.75). CONCLUSIONS: Immunotherapy suppresses skin test sensitivity 8-16 years after discontinuation of treatment, but long-term effects on specific IgE levels in serum are not observed. Broad-spectrum immunotherapy does not appear to affect the acquisition of new inhalant sensitivities.

Adolescent↗
PubMed2006

Clinical and entomological factors influence the outcome of sting challenge studies.

BACKGROUND: The reported frequency of systemic reactions to challenge sting varies greatly. OBJECTIVE: To evaluate the interaction of clinical and entomological factors that determine the outcome of a challenge sting. METHODS: Patients allergic to yellow jacket were stung and monitored for systemic reaction. The frequency and severity of sting reactions were analyzed in relation to the species of insect used and patient characteristics. RESULTS: Objective systemic reactions occurred in 21 of 69 patients (30%) stung with Vespula maculifrons and in 8 of 71 patients (11%) with Vespula germanica (P=.005). Systemic reactions were more frequent in patients with a severe history (9/30; 30%) than in those with a mild or moderate history (21/145; 14%; P=.04). In only 1 of 111 patients (0.9%) was the reaction to sting challenge more severe than previous reactions. The reaction rate was higher when venom skin tests were positive at <1.0 microg/mL (17/75=23%) than when sensitivity was milder (9/100=9%; P=.012). We compared sting outcome and venom-induced histamine release in relation to insects collected in July or in October, and found no difference. CONCLUSION: Allergic reactions to sting challenge are determined by the species of yellow jacket used, the severity of previous sting reactions, and the degree of skin test sensitivity, but not by the time of year. These factors are important to clinicians when they evaluate the chance of reaction to a future sting and to researchers when they design and report sting challenge studies.

Adult↗
PubMed2006

Accuracy of US Food and Drug Administration-cleared IgE antibody assays in the presence of anti-IgE (omalizumab).

BACKGROUND: Although serological IgE measurements can aid in efficacy assessment of patients with asthma on omalizumab (Xolair [Genentech, Inc., South San Francisco, Calif]; humanized IgG1 antihuman IgE Fc), its effect on clinically used IgE assay performance is unknown. OBJECTIVE: This study investigated the hypothesis that IgE:IgG-anti-IgE immune complex formation after omalizumab administration diminishes accuracy and increases variability of IgE assays performed in diagnostic immunology laboratories. METHODS: Plasma from 4 atopic adults was incubated with omalizumab (50 or 200 molar excess to IgE) or buffer. Paired specimens were sent masked to 159 clinical laboratories in the College of American Pathologists Diagnostic Allergy Proficiency Survey (cycles SE-C-2003, SE-A-2005). Inhibitory effects produced by omalizumab on accuracy and reproducibility of US Food and Drug Administration (FDA)-cleared total and allergen-specific IgE assays were computed by using national proficiency survey data. RESULTS: Total serum IgE levels measured in the 2 ImmunoCAP assays were minimally reduced (2.4-9.0%) by the presence of omalizumab, whereas 5 other assays showed marked reductions from 12.5% to 67.2% (P < .001) that increased in proportion to total serum IgE levels. The degree of interference was not large enough to produce detectable misclassification of IgE antibody results (positive to negative) in 4 multiallergen screening assays. Of 11 FDA-cleared IgE antibody assays, only 3 (ImmunoCAP, UniCAP, Immulite-2000) generated quantitative IU/mL results that could be assessed for interference. Omalizumab produced 0.8% to 27.8% reduction in allergen-specific IgE levels across 8 allergen specificities. CONCLUSION: Although as much as 62% loss in accuracy was observed in FDA-cleared human IgE assays, the ImmunoCAP system was sufficiently robust to provide accurate and reproducible total and allergen-specific IgE antibody results in a clinical setting where therapeutic levels of omalizumab are present in serum. CLINICAL IMPLICATIONS: Accurate monitoring of total and allergen-specific IgE, together with free IgE levels, in serum from patients on omalizumab may help optimize dosing and maximize the efficacy of Xolair therapy.

Adult↗
PubMed2006

Latex specific IgE: performance characteristics of the IMMULITE 2000 3gAllergy assay compared with skin testing.

BACKGROUND: In the absence of a US Food and Drug Administration (FDA)-cleared latex skin testing reagent, in vitro tests remain important for the diagnosis of latex allergy. OBJECTIVE: To evaluate the performance characteristics of IMMULITE 2000 3gAllergy (Immulite), a third-generation, FDA-cleared, continuous random-access immunoanalyzer, for the quantification of latex specific IgE. METHODS: Stored serum samples (N = 201) from patients classified as having positive or negative latex puncture skin test results were measured for latex specific IgE levels using Immulite, and these data were compared with historical results from 3 second-generation, FDA-cleared IgE antilatex assays (AlaSTAT [Ala], AutoCAP [CAP], and HY*TEC enzyme immunoassay [HT]). RESULTS: The diagnostic performances of the CAP, Ala, and Immulite assays (> or = 0.35 kU/L cutoff value) were equivalent in sensitivity and specificity (P > .05). The HT assay (> or = 0.05 kU/L cutoff value) was more sensitive and less specific (P < .05). Immulite (> or = 0.10 kU/L cutoff value) had greater sensitivity than Ala and CAP and greater specificity than HT (P < .05 for both). Diagnostic efficiency was greater for Immulite than for CAP, Ala, and HT (P < .05). CONCLUSIONS: The Immulite system is superior in diagnostic performance, especially at the 0.10 kU/L or greater cutoff level, for the diagnosis of latex allergy compared with older, second-generation assays. Immulite still misclassifies 15.5% of puncture skin test-positive individuals as negative for latex specific IgE. Compared with second-generation assays, Immulite represents a technological advance, with enhanced speed and less operator intervention.

Humans↗
PubMed2006

Should heterogeneity be the basis for conservation? Grassland bird response to fire and grazing.

In tallgrass prairie, disturbances such as grazing and fire can generate patchiness across the landscape, contributing to a shifting mosaic that presumably enhances biodiversity. Grassland birds evolved within the context of this shifting mosaic, with some species restricted to one or two patch types created under spatially and temporally distinct disturbance regimes. Thus, management-driven reductions in heterogeneity may be partly responsible for declines in numbers of grassland birds. We experimentally altered spatial heterogeneity of vegetation structure within a tallgrass prairie by varying the spatial and temporal extent of fire and by allowing grazing animals to move freely among burned and unburned patches (patch treatment). We contrasted this disturbance regime with traditional agricultural management of the region that promotes homogeneity (traditional treatment). We monitored grassland bird abundance during the breeding seasons of 2001-2003 to determine the influence of altered spatial heterogeneity on the grassland bird community. Focal disturbances of patch burning and grazing that shifted through the landscape over several years resulted in a more heterogeneous pattern of vegetation than uniform application of fire and grazing. Greater spatial heterogeneity in vegetation provided greater variability in the grassland bird community. Some bird species occurred in greatest abundance within focally disturbed patches, while others occurred in relatively undisturbed patches in our patch treatment. Henslow's Sparrow, a declining species, occurred only within the patch treatment. Upland Sandpiper and some other species were more abundant on recently disturbed patches within the same treatment. The patch burn treatment created the entire gradient of vegetation structure required to maintain a suite of grassland bird species that differ in habitat preferences. Our study demonstrated that increasing spatial and temporal heterogeneity of disturbance in grasslands increases variability in vegetation structure that results in greater variability at higher trophic levels. Thus, management that creates a shifting mosaic using spatially and temporally discrete disturbances in grasslands can be a useful tool in conservation. In the case of North American tallgrass prairie, discrete fires that capitalize on preferential grazing behavior of large ungulates promote a shifting mosaic of habitat types that maintain biodiversity and agricultural productivity.

Agriculture↗
PubMed2005

Human metapneumovirus infection plays an etiologic role in acute asthma exacerbations requiring hospitalization in adults.

We determined the prevalence of human metapneumovirus (hMPV) infection in adults with asthma who were prospectively enrolled after hospitalization for an acute asthma exacerbation. Nasal wash specimens collected at admission and 3 months after discharge were tested for hMPV by real-time reverse-transcription polymerase chain reaction assays. hMPV was detected in 7 (6.9%) of 101 subjects at hospitalization and in 1 (1.3%) of 75 subjects at follow-up (odds ratio, 7 [95% confidence interval, 0.9-312]; P=.03). None of the patients with hMPV infection at hospitalization tested positive at follow-up, strongly suggesting that hMPV plays a direct etiologic role in acute asthma exacerbations.

Acute Disease↗
PubMed2005

Humoral immune response in acute hepatitis C virus infection.

BACKGROUND: There is little information on the timing, magnitude, specificity, and clinical relevance of the antibody response to acute hepatitis C virus (HCV) infection. We investigated the specificity, titer, and neutralizing potential of antibody responses to acute infection by examining 12 injection drug users before, during, and after infection. METHODS: Seroconversion was defined as incident detection of HCV-specific antibodies by using a commercially available enzyme-linked immuosorbent assay (ELISA). HCV protein-specific antibody responses were measured using recombinant antigens in an ELISA. For neutralization assays, plasma was incubated with human immunodeficiency virus (HIV)-HCV H77 or control HIV-murine leukemia virus (MLV) pseudotype virus and then allowed to infect Hep3B hepatoma cells. RESULTS: The mean time to HCV seroconversion was 6 weeks after the onset of viremia. Antibody responses to nonstructural proteins were detected before responses to the structural proteins, and antibodies to both were primarily restricted to the immunoglobulin G1 (IgG1) subclass. The maximum median end point titers for antibody responses to structural and nonstructural proteins were 1 : 600 and 1 : 6400, respectively. Antibodies that neutralized a retroviral pseudotype bearing HCV 1a envelope glycoproteins were detected at seroconversion in only 1 subject and at 6-8 months after seroconversion in 3 subjects. The delayed appearance of neutralizing antibodies was consistent with the late development of antibodies specific for the viral envelope glycoproteins, which are believed to mediate virus neutralization. CONCLUSION: The humoral immune response to acute HCV infection is of relatively low titer, is restricted primarily to the IgG1 subclass, and is delayed. A better understanding of why production of neutralizing antibody is delayed may improve efforts to prevent HCV infection.

Acute Disease↗
PubMed2005

Assessment of indoor allergen exposure.

Of the four modes of treating human allergic disease, avoidance or separation of the allergic patient from the allergen source is most effective and least expensive. The clinical immunology laboratory has established efficient and inexpensive "reservoir" dust sampling and processing procedures to obtain a surface dust specimen that reflects the allergen burden of the environment. Following extraction, allergens are quantified by reproducible, validated immunoenzymetric assays for the quantification of "indicator" aeroallergen levels in home, school, and work environments. In this paper, the strategies and methods for collecting and processing dust samples are discussed, and assays are reviewed for quantifying indoor aeroallergen exposure from dust mites (Der p 1 and 2, Der f 1 and 2), animals (cat: Fel d 1; dog: Can f 1; mouse: Mus m 1; rat: Rat n 1), and insects (cockroach: Bla g 1 and 2). Accurate quantification of the levels of allergen in indoor environments facilitates avoidance therapy by identifying environmental risk factors for asthma and allergy exacerbation and allowing the allergic patient to monitor the effectiveness of environmental remediation actions.

Air Pollution, Indoor↗
PubMed2005

Adult asthma severity in individuals with a history of childhood asthma.

BACKGROUND: Childhood asthma can have a range of outcomes in adulthood. OBJECTIVE: To identify clinical features and exposures associated with persistence and severity of childhood asthma in adulthood. METHODS: Eighty-five of 121 subjects previously enrolled in a study of immunotherapy for childhood allergic asthma (age 5-12 years) were re-evaluated with allergy skin testing, spirometry, and interviews about asthma symptoms and medications. These young adults (age 17-30 years; 74% male) all had moderate to severe childhood asthma. Adult asthma severity was scored by using a modified version of National Heart, Lung, and Blood Institute severity categories. RESULTS: Thirteen (15.3%) of 85 adult subjects were in remission despite persistent childhood asthma. Another 19 subjects (22.4%) had only intermittent asthma. The remaining 53 had persistent asthma, of whom 12 (14.1%) had mild asthma, 25 (29.4%) had moderate asthma, and 16 (18.8%) had severe asthma. Subjects in remission, compared with subjects with intermittent or persistent asthma, had lower total serum IgE in childhood (412 ng/mL vs 1136 ng/mL vs 968 ng/mL; P = .02) and fewer positive allergy skin tests (7 vs 9 vs 10 from panel of 18; P = .02). Subjects in remission also had milder childhood asthma, indicated by lower average daily medication usage scores (1.6 vs 3.5 vs 4.4; P = .005) and lower percentage of days on inhaled corticosteroids (13.7% vs 24.7% vs 40.9%; P = .008). No significant association was found between current asthma severity and childhood immunotherapy ( P = .46). CONCLUSION: The prognosis of childhood allergic asthma in adulthood is largely determined early in life. The degree of atopy appears to be a critical determinant of asthma persistence.

Administration, Inhalation↗
PubMed2005

Increased expression of osteopontin is associated with long-term bee venom immunotherapy.

BACKGROUND: Venom allergen immunotherapy (VIT) is proven to be highly effective for insect allergy, but the mechanisms and the biomarkers associated with clinical efficacy remain elusive. OBJECTIVE: The aim of this study was to identify candidate biomarkers associated with successful VIT. METHODS: Gene chip array and clustering analyses of PBMCs from subjects with or without VIT were performed. RESULTS: From gene chip array and clustering analyses, an increased expression of osteopontin was found in patients who completed 5 to 6 years of VIT and discontinued therapy for 3 to 6 years (completed treatment group) compared with the untreated group. A significantly higher level of serum osteopontin was found in the completed treatment group compared with the untreated group (n = 16 in each group; P < .001). CONCLUSION: The upregulation of osteopontin after VIT suggests a role of osteopontin as a candidate biomarker for VIT.

Adult↗
PubMed2005

Proficiency testing of allergen measurements in residential dust.

BACKGROUND: Analyses of household dust for allergens are more common with increased efforts to reduce and control asthma. Currently, no laboratory accreditation or quality assurance program specific to household dust allergen analyses exists. Moreover, there is an absence of peer-reviewed data on within-laboratory and between-laboratory variability that is achievable for these analyses. OBJECTIVES: The purpose of this study was to characterize the levels of intralaboratory and interlaboratory variability in analyses of allergen concentrations in residential dust and to investigate the utility of quality control samples for monitoring laboratory performance. METHODS: Aliquots from homogeneous batches of dust and dust extracts were provided to 8 commercial, academic, and municipal laboratories to be analyzed for as many as 6 allergens (Der p 1, Der f 1, Fel d 1, Can f 1, Bla g 1, Mus m 1) by using ELISA techniques. RESULTS: Coefficients of variation on the estimated geometric means from the analytical results ranged between 61% and 93%. In most cases, between-laboratory variability was the dominant component of total variability. In spite of this between-laboratory variability, reasonable agreement was observed between the means of allergen levels in the reference laboratory characterizations and the estimated geometric means from the model fitting of results across participating laboratories. CONCLUSION: The results from this study indicate that, in most cases, participating laboratories could measure the concentrations of allergens by using ELISA procedures with a level of accuracy and precision that may be acceptable in many situations.

Allergens↗
PubMed2005

Immunological methods for quantifying free and total serum IgE levels in allergy patients receiving omalizumab (Xolair) therapy.

Omalizumab (humanized-IgG1 anti-human IgE Fc, Xolair) complexes circulating IgE, blocking IgE binding to high affinity epsilon Fc receptors (FcepsilonR1) on mast cells and basophils. Free (non-Omalizumab bound) IgE levels in serum are a measure of effective Omalizumab dosing. The goal of this study was to quantify free (non-Omalizumab-complexed) and total serum IgE levels in asthma patients on Xolair. The concentration of (non-Omalizumab bound) free IgE in human serum was measured using a solid phase immunoenzymetric assay (IEMA) in which IgE was captured from serum with monoclonal anti-human IgE (clone HP6061) and detected with labeled-FcepsilonR1alpha. In a companion total human serum IEMA, IgE was captured from serum with the same anti-human IgE (clone HP6061) and all bound IgE was detected with labeled monoclonal anti-human IgE Fc (clone HP6029). Free and total IgE levels were quantified in pre- and 1 and 3 months post Omalizumab therapy sera from 12 allergic asthma patients. In the absence of Omalizumab, working ranges of the free and total IgE IEMAs were comparable (10-1000 kIU/l), with excellent precision, reproducibility and parallelism. Pre-Omalizumab total and free IgE levels by IEMA were highly correlated (r2=0.99, Y=0.9X+0.32, p<0.001), as were total serum IgE levels by IEMA and ImmunoCAP-250 (r2=0.98, Y=1.1X-0.05, p<0.001, n=33). In vitro reduction of free IgE (>90%) occurred at [Omalizumab:IgE] molar ratios of 2-20. Total IgE levels in 12 asthmatics increased from pre-therapy levels (52-658 kIU/l) by 1.5-5.5-fold at 1 month and 1.7-8.6 fold at 3 months of uninterrupted Omalizumab treatment. Free IgE levels fell by 49%-97% at 1 month and 45%-98% by 3 months of Omalizumab treatment. Free and total IgE levels by IEMA aid in monitoring patients receiving Omalizumab therapy.

Adult↗
PubMed2005

Contamination of nebulizers with environmental allergens.

BACKGROUND: A previous article described cockroach allergen in the nebulizer reservoir of an asthmatic patient who experienced a life-threatening exacerbation after nebulizer use. OBJECTIVE: To determine whether indoor allergens can be measured in home nebulizers. METHODS: As part of a large study examining nebulizer use in underserved asthmatic children, visiting nurses replaced nebulizer sets in patients' homes. Twenty used sets were randomly selected for analysis, without linkage to clinical or home environmental data. Nebulizer reservoirs and negative controls (buffer and albuterol) were extracted overnight with 2 mL of buffer. For positive controls, nebulizer sets were placed in homes with cats and dogs, and other reservoirs were intentionally contaminated with cat (Fel d 1), dog (Can f 1), cockroach (Bla g 1 and Bla g 2), and mouse (Mus m 1) skin test solutions. Extracts were tested for allergens in a masked manner using enzyme-linked immunosorbent assay. RESULTS: Of 17 reservoirs with adequate specimens for allergen detection, 5 (29%) had measurable levels for at least 1 of 5 allergens tested. One reservoir had measurable Can f 1, 2 had Bla g, 3 had Mus m 1, and none had Fel d 1 allergen. Two of 3 homes with cats where nebulizer setups were placed had measurable Fel d 1 in the reservoir, and 1 of 2 homes with dogs had measurable Can f 1. Reservoirs kept in sealed plastic bags had no detectable allergen. CONCLUSIONS: Indoor allergens can be found in the nebulizer equipment of children with asthma, with the potential for adverse consequences. Storing nebulizer sets in sealed plastic bags may prevent contamination.

Allergens↗
PubMed2005

Genetic predisposition to latex allergy: role of interleukin 13 and interleukin 18.

BACKGROUND: Occupational exposure of healthcare workers to natural rubber latex has led to sensitization and potentially life-threatening anaphylaxis. Although environmental exposure to natural rubber latex products is necessary for sensitization, it is not sufficient. A number of genetic factors also seem to contribute to the latex sensitization; however, the multigenic nature of the allergic phenotype has made the identification of susceptibility genes difficult. The current study tests the hypothesis that known functional polymorphisms in genes encoding interleukin 4, interleukin 13, and interleukin 18 occur in a higher frequency in healthcare workers with natural rubber latex allergy. METHODS: Four hundred thirty-two healthcare workers with occupational exposure to natural rubber latex were screened using a clinical history questionnaire and latex-specific immunoglobulin E serology. Genomic DNA was extracted from peripheral blood lymphocytes and analyzed for single-nucleotide polymorphisms in candidate genes of interest. Data from cases and controls were analyzed by nominal logistic regression, with P < 0.05 considered significant. RESULTS: The latex allergy phenotype was significantly associated with promoter polymorphisms in IL13 -1055 (P = 0.02), IL18 -607 (P = 0.02), and IL18 -656 (P = 0.02) compared with nonatopic controls. CONCLUSIONS: The significant association of IL13 and IL18 promoter polymorphisms with latex allergy suggests a potential location for genetic control in the induction of latex allergy in individuals and extends the understanding of the genetic basis for the induction of immediate-type hypersensitivity in healthcare workers occupationally exposed to natural rubber latex.

Adult↗