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Biomedical subjects

R G Hamilton

Publications and source records attributed to R G Hamilton.

At least 55 records · Page 3Linked to original sources

Laboratory analyses in the diagnosis of human allergic disease.

The clinical immunology laboratory provides support to the allergist in the diagnosis and management of human allergic diseases. Following a clinical history, the detection of allergen-specific immunoglobulin E (IgE) in serum can be useful in the definitive diagnosis of an IgE antibody-mediated hypersensitivity. Total serum IgE, the multiallergen screen, and mast cell tryptase are less commonly measured analytes in the work-up of the allergic patient. More recently, the clinical laboratory has employed monoclonal antibody based-enzyme immunoassays to quantify dust mite, cat, dog, and cockroach indicator aeroallergen levels in indoor home and work environments. Levels of allergenic proteins in environmental and medical/consumer products are measured by other assays such as the competitive inhibition radioallergosorbent test. Methods of quantification, internal quality control, and external proficiency testing programs are emphasized in this report.

Allergens↗

Environmental allergen analyses.

Environmental specimens (dust) from indoor home, school, and work-place environments can be evaluated for the content of aeroallergens produced by dust mite, cat, dog, cockroach, and molds, as a means of determining exposure risk and facilitating avoidance therapy. This article examines the variables that influence the levels of these allergens in indoor environments, methods for sampling, clinical laboratory assays used for testing, and interpretation of aeroallergen results for making decisions about remediation.

Air Pollution, Indoor↗

A double-blind study of the discontinuation of ragweed immunotherapy.

BACKGROUND: Immunotherapy effectively treats the symptoms of allergic rhinitis and improves its pathophysiology. We studied whether the effects of immunotherapy on the early response to nasal challenge with antigen and seasonal symptoms persist after discontinuation. METHODS: Twenty subjects with ragweed allergy who were receiving immunotherapy and who had nasal challenges performed before initiation of treatment were selected. The patients had been receiving maintenance therapy with aqueous ragweed extract at a dose of 12 microg of Amb a 1 equivalent for a minimum of 3 years, at which point they were randomized to receive either placebo injections or to continue with the maintenance dose. Nasal challenges were performed before and 1 year after randomization. Nasal challenges were monitored by counting the number of sneezes and measuring histamine, N-alpha-tosyl-L-arginine methyl ester-esterase activity, and kinins in recovered nasal lavages. In the same year symptom diaries were collected during the ragweed season. RESULTS: The initial immunotherapy significantly reduced responses to nasal challenge in both groups. The group continuing to receive active treatment showed no significant changes from the response before randomization. In contrast, the group randomized to placebo treatment showed a partial return of histamine, kinins, and N-alpha-tosyl-L-arginine methyl ester-esterase in nasal secretions and the numbers of sneezes. IgG antibodies to ragweed declined only in the group switched to placebo treatment. Seasonal rises of IgE antibodies to ragweed did not return during the first season after treatment was stopped. Symptoms reported during the ragweed season were not different between the groups. CONCLUSIONS: One year after discontinuation of ragweed immunotherapy, nasal challenges showed partial recrudescence of mediator responses even though reports during the season appeared to indicate continued suppression of symptoms.

Adolescent↗

Validation of the latex glove provocation procedure in latex-allergic subjects.

BACKGROUND: A latex provocation test is needed to clarify the allergic status of patients who present with a positive clinical history for latex allergy and a negative latex skin test and/or serologic test. OBJECTIVE: In the present study, we aimed to optimize and validate the performance and safety of a latex glove provocation protocol and to employ it to verify the barrier properties of the Dermapor expanded polytetrafluorethylene (ePTFE) glove liner (liner) for latex glove allergen. METHODS: Twenty-one skin test positive latex-allergic subjects donned goggles and a silicone mask, washed their hands and then put high allergen-containing latex gloves (mean = 15,072 AU/mL) on a moist, bare and liner-covered hand. Due to an absence of verifiable reactions on the bare hand in the first five subjects, the protocol was modified to puncture the skin in three sites on the hand prior to donning the liner/glove or latex glove alone. Subjects were observed for 30 minutes for localized allergic symptoms (pruritus and hives). Lined and unlined hands were compared for reactions. RESULTS: Application of highly allergenic latex gloves onto the bare hands of five skin test-positive, latex-allergic subjects produced some mild pruritus but no visually detectable dermatitis. In contrast, all 17 latex-allergic subjects who underwent the modified glove challenge protocol involving a puncture prior to glove application experienced intense pruritus with measurable wheals and erythema at sites where their skin was punctured. Equivalent wheal and erythema reactions were observed at a site where a puncture was performed directly through the glove. These same subjects experienced no pruritus or hives on their opposite hands that received a liner prior to latex glove application. CONCLUSIONS: Direct application of highly allergenic latex gloves onto the hands of skin test-positive, latex-allergic individuals does not commonly produce localized allergic symptoms after minutes, especially if the subject has successfully avoided latex and has no evidence of dermatitis. By puncturing the skin prior to latex glove donning, quantifiable hives are produced within 15 minutes following glove application. A Dermapor ePTFE liner prevents the transfer of allergen from gloves onto the skin and therefore can serve to minimize contact exposure as part of avoidance therapy.

Adult↗

Grass immunotherapy induces inhibition of allergen-specific human peripheral blood mononuclear cell proliferation.

The peripheral blood mononuclear cells (PBMC) from humans allergic to grass pollens (GR+ subjects) show strong in vitro proliferative responses to purified allergens from Lolium perenne pollen Lol p 1, and to a lesser extent to Lol p 2 and Lol p 3. By contrast, PBMC from grass allergic patients undergoing immunotherapy (GR + IT subjects) exhibit a very poor Lol p-specific proliferative response, similar to that observed in nongrass allergic subjects (GR-subjects). Unlike GR-subjects, both GR+ and GR + IT subjects have high levels of antigen-specific serum IgG and IgE antibodies to Lol p 1, Lol p 2 and Lol p 3. While GR+ subjects exhibit a significant correlation between antigen-specific serum antibody and PBMC responses, GR + IT subjects do not show a correlation between the two responses. The possible mechanisms by which immunotherapy may modulate allergen-specific T cell proliferative response are discussed.

Adult↗

Evaluation of monoclonal antibodies with specificity for human IgA, IgA subclasses and allotypes and secretory component. Results of an IUIS/WHO collaborative study.

51 monoclonal antibodies (McAb) with putative specificity for human IgA, the IgA subclasses, Am allotypes or secretory component (SC) were evaluated for immunoreactivity and specificity by nine laboratories employing immunodiffusion, agglutination, immunohistological assays, immunoblotting and direct binding and competitive inhibition enzyme immunoassays. McAbs specific for IgA PAN (n = 24), IgA1 (n = 7), IgA2 (n = 3), IgA2m(2) (n = 2), non-IgA2m(2) (n = 4) and SC or secretory IgA (n = 5) were identified that were immunoreactive and specific in the assays employed. The McAbs identified as IgA- or SC-reactive were shown to be non-reactive to human IgG, IgM, IgD, IgE, kappa and lambda by direct binding and competitive inhibition immunoassays. Interestingly, no McAbs with restricted specificity for IgA2m(1) were identified. Some McAbs displayed higher affinity and/or better performance in one or several of the assay groups. The IgA- and SC-specific McAbs identified in this international collaborative study have potential as immunochemical reference reagents to identify and quantitate monomeric and polymeric IgA in human serum and secretions.

Animals↗

The 14.6 kd rubber elongation factor (Hev b 1) and 24 kd (Hev b 3) rubber particle proteins are recognized by IgE from patients with spina bifida and latex allergy.

Two major water-insoluble proteins are located on the surface of rubber particles in Hevea brasiliensis latex. A 14.6 kd protein (Hev b 1), found mainly on large rubber particles (> 350 mm in diameter), and a 24 kd protein (Hev b 3), found mainly on small rubber particles (average diameter, 70 nm), are recognized by IgE from patients with spina bifida and latex allergy. Although Hev b 1 (also called the rubber elongation factor [REF]) has previously been reported as a major latex allergen, this conclusion has been disputed on the basis of results from other studies. The allergenicity of Hev b 1 is verified in this study by testing the recombinant protein generated from its gene. Because allergenicity is confined to patients with spina bifida and not observed in adults sensitive to latex, it is not a major latex allergen. The identification of Hev b 3 as another allergen originating from rubber particles is confirmed by immunogold labeling and electron microscopy. Observations with the monoclonal antibody USM/RC2 developed against Hev b 3 show that the protein has a tendency to fragment into several polypeptides of lower molecular weight (from 24 kd to about 5 kd) when stored at -20 degrees C. There is also indication of protein aggregation from the appearance of proteins with molecular weights greater than 24 kd. Fragmentation of Hev b 3 is induced immediately on he addition of latex B-serum, which is normally compartmentalized in the lutoids in fresh latex. In the preparation of ammoniated latex (used for the manufacture of latex products), the lutoids are ruptured, and the released B-serum reacts with Hev b 3 on the rubber particles to give rise to an array of low molecular weight polypeptides that are allergenic to patients with spina bifida.

Adult↗

Exposure and sensitization to environmental allergen of predominantly Hispanic children with asthma in San Diego's inner city.

BACKGROUND: Environmental living conditions co-sorting with economic status may influence the disease morbidity rate of childhood asthma in ethnic minority urban poor populations. OBJECTIVES: This study was carried out to assess exposure and sensitization to environmental allergens in southeast San Diego children with current asthma-related symptoms and to determine the utility of environmental control measures. METHODS: Children, 9 to 12 years old, with current asthma-related symptoms were identified and enrolled at four school sites. Skin prick testing with aeroallergens was performed, and allergen in collected dust (from mattresses, pillows, and bedroom carpets) was quantified by enzyme immunoassay. Environmental control instruction and products were provided. RESULTS: Of 41 subjects who underwent skin testing, 51.2% were reactive to environmental allergens (39% to mite, 22% to cockroach, and 9.8% to cat). Mean allergen levels for sensitized subjects were: Der p 1 (11 subjects), 18,722 ng/gm dust; Der f 1 (8 subjects), 5345 ng/gm dust; Fel d 1 (3 subjects), 214 ng/gm dust; Bla 1 (8 subjects), 7.15 U/gm dust; and Bla 2 (8 subjects) 7.13 U/gm dust. Environmental allergen exposure levels were not significantly different between sensitized and nonsensitized subjects. Environmental control measures for mite exposure were completed in six homes of sensitized subjects. One month after treatment, allergen levels fell 91.2% for Der p 1, 98.9% for Der f 1, and 88.2% for Fel d 1. One year after treatment, mite and cat allergen levels remained low. Environmental control had no consistent impact on cockroach allergen levels. CONCLUSION: Environmental allergen sensitization and exposure may be cofactors contributing to increased disease severity in urban poor populations.

Air Pollutants↗

Socioeconomic status and race as risk factors for cockroach allergen exposure and sensitization in children with asthma.

BACKGROUND: The domestic cockroach has been identified as an important source of indoor aeroallergens worldwide in both temperate and tropical climates. Because cockroach populations are highest in crowded urban areas, some have suggested that the increased asthma morbidity and mortality rates in inner cities could be related in part to cockroach allergen exposure. We have examined cockroach allergen exposure in the homes of children with asthma in both urban and suburban locations and have related the rates of exposure and sensitization to socioeconomic, racial, and demographic factors. OBJECTIVE: The study was designed to determine the independent contribution of race, socioeconomic status, and place of residence to the risk of cockroach allergen exposure and sensitization in children with asthma. METHODS: Eighty-seven children with moderate to severe allergic asthma, aged 5 to 17 years, participating in a prospective trial of immunotherapy, were evaluated. Extracted dust samples from three home locations were analyzed by using two-site monoclonal immunoassays for major cockroach allergens (Bla g 1 and Bla g 2). A puncture skin test with a mixed cockroach allergen extract was performed in 81 of the 87 subjects. RESULTS: In the 87 homes evaluated, 26% of the bedroom dust samples had detectable levels of cockroach allergen. In homes with detectable bedroom cockroach allergen levels, mean Bla g 1 and Bla g 2 concentrations in urban and suburban homes were similar. Over 80% of children with bedroom Bla g 1 or Bla g 2 of 1 U/gm or greater demonstrated skin sensitivity to cockroach allergen. The rate of cockroach sensitization was directly related to the level of bedroom exposure. African-American race was the only factor that was independently associated with cockroach allergen exposure (p = 0.05). Lower socioeconomic status, age greater than 11 years, cockroach exposure, and African-American race were all independently associated with cockroach allergen sensitization on the basis of stepwise multiple linear regression analysis. CONCLUSIONS: African-American race and low socioeconomic status were both independent, significant risk factors for cockroach allergen sensitization in children with atopic asthma. Cockroach allergen is detectable throughout the house, including the critical bedroom environment.

Adolescent↗

Natural rubber latex skin testing reagents: safety and diagnostic accuracy of nonammoniated latex, ammoniated latex, and latex rubber glove extracts.

BACKGROUND: Nonammoniated latex, ammoniated latex, and rubber glove extracts are the only sources of natural rubber (Hevea brasiliensis) latex that have potential for use as skin testing reagents in the diagnosis of latex allergy. Their diagnostic sensitivity and specificity as skin test reagents are unknown. OBJECTIVE: We conducted a phase 1/2 clinical study to examine the safety and diagnostic accuracy (sensitivity and specificity) of nonammoniated latex, ammoniated latex, and rubber glove extracts as skin test extracts to identify the most efficacious source material for future skin test reagent development. METHODS: Twenty-four adults not allergic to latex, 19 adults with hand dermatitis or pruritus, and 59 adults with a latex allergy were identified by clinical history. All provided blood and then received puncture skin tests and intradermal skin tests with nonammoniated latex, ammoniated latex, and rubber glove extracts from Malaysian H. brasiliensis latex by use of sequential titration. A glove provocation test and IgE anti-latex RAST were used to clarify positive history-negative skin test response and negative history-positive skin test response mismatches. RESULTS: All three extracts were biologically safe and sterile. After normalization to 1 mg/ml of total protein, all three extracts produced equivalent diagnostic sensitivity and specificity in puncture skin tests and intradermal skin tests at various extract concentrations. Optimal diagnostic accuracy was safely achieved at 100 micrograms/ml for intradermal skin tests (e.g., nonammoniated latex: puncture skin test sensitivity 96%, specificity 100%; intradermal skin test sensitivity 93%, specificity 96%). The presence of IgE antibody in skin was highly correlated with IgE anti-latex in serum (nonammoniated latex: r = 0.98, p < 0.001; ammoniated latex: r = 0.94, p < 0.001; rubber glove extract: r = 0.96, p < 0.001). All five available subjects with a positive history, negative skin test response, and absence of IgE antibody in serum had a negative glove provocation test response, indicating no clinical evidence of latex allergy. No systemic or large local allergic reactions were observed with puncture skin tests or intradermal skin tests. CONCLUSIONS: Equivalent diagnostic sensitivity and specificity were observed with the nonammoniated latex, ammoniated latex, and rubber glove extract skin test reagents after normalization for total protein; nonammoniated latex may be considered the reagent of choice on the basis of practical quality control and reproducibility considerations.

Adult↗

Absence of cross-reactivity of IgE antibodies from subjects allergic to Hevea brasiliensis latex with a new source of natural rubber latex from guayule (Parthenium argentatum).

BACKGROUND: Natural rubber latex sensitization is caused by proteins from the latex of Hevea brasiliensis, the Brazilian rubber tree. Alternative non-cross-reactive latex rubber sources are needed for the manufacture of nonallergenic medical devices (e.g., catheters) that require elasticity, which is not currently provided by synthetic materials. METHODS: We have studied the ability of IgE antibodies from subjects allergic to Hevea latex and IgG antibodies from hyperimmunized mice to detect proteins derived from guayule (Parthenium argentatum), an alternative rubber source, using a direct binding and competitive inhibition RAST and Western blot analysis. RESULTS: IgE antibodies from 62 subjects allergic to Hevea latex (46 adults and 16 children with spina bifida) and from serum pools of adults allergic to Hevea latex (n = 183), pediatric patients (n = 101), and patients with spina bifida (n = 53), as well as IgG antibodies from hyperimmunized mice, were unable to detect any proteins in guayule by RAST or Western blot analysis. No competitive inhibition of IgE anti-Hevea binding to Hevea solid phase was detected by the preincubation of sera from subjects allergic to Hevea latex with soluble guayule latex before RAST analysis. CONCLUSIONS: These results demonstrate that proteins in guayule latex are not cross-reactive with Hevea latex allergens. Devices that require the elasticity provided by rubber may be manufactured with guayule latex as an alternative rubber source for patients with Hevea latex allergy.

Adult↗

Single doses of intravenous protamine result in the formation of protamine-specific IgE and IgG antibodies.

BACKGROUND: Protamine reactions are a well-recognized and serious complication of intravenous protamine administration. IgE-mediated anaphylaxis occurs after initial sensitization and subsequent re-exposure to antigens. Subcutaneous protamine in insulin preparations is associated with protamine-specific IgE and IgG antibody production. In contrast, the influence of intravenous protamine administration on protamine-specific IgE and IgG antibody formation has never been investigated. METHODS: Sera from 93 patients were analyzed for protamine-specific IgE and IgG antibodies both before and 4 to 6 weeks after exposure to single doses of intravenous protamine. Specific clinical variables were assessed by univariate and multivariate analyses to determine independent predictors of protamine-specific antibody production. RESULTS: In patients who were previously seronegative, intravenous protamine administration resulted in protamine-specific IgE and IgG antibody production in 17 of 93 (18%) and 15 of 93 (16%) patients, respectively. As determined by multivariate analysis, male gender (p = 0.06) and insulin-dependent diabetes mellitus (p = 0.002) were associated with protamine-specific IgG but not IgE antibody production. CONCLUSION: Single-dose intravenous protamine resulted in protamine-specific IgE and/or IgG antibody production in 26 of 93 (28%) of patients. Seroconversion was associated with male gender and insulin-dependent diabetes mellitus. Patients responding immunologically to protamine may be at increased risk for experiencing reactions on subsequent exposure.

Aged↗

Prevalence of latex-specific IgE antibodies in hospital personnel.

BACKGROUND: Rubber latex hypersensitivity is an important concern for health care workers. PURPOSE: The Center for Devices and Radiological Health, in collaboration with the Consumer Product Safety Commission, conducted a multicenter study of the prevalence of latex-specific IgE antibodies among United States hospital personnel. MATERIALS AND METHODS: Nine hospitals participated in the cross-sectional study. A total of 504 hospital personnel completed questionnaires that provided an array of demographic, occupational, and clinical information, including a history, if any, of allergies and the use of latex and nonlatex gloves. More than three-quarters (76.5%) of the participants were tested for total IgE and latex specific IgE. RESULTS: A total of 21 (5.5%, 95% CI = 3%-7%) of the tested participants were positive for the presence of latex specific IgE antibodies, defined as a latex IgE level of > or = 0.6 ng/mL. Latex specific IgE antibodies were more prevalent in participants who reported tachycardia, palpitations, flushing, or wheezing associated with latex gloves (Odds Ratio = 10.2, 95% CI = 3.7-28.6). CONCLUSION: The study's results suggest that the prevalence of latex-specific IgE antibodies among hospital personnel is appreciable and these personnel and their health care providers should be aware of this entity.

Adult↗

Effect of human immunodeficiency virus type 1 infection on the antibody response to a glycoprotein conjugate pneumococcal vaccine: results from a randomized trial.

Adults (n = 282) were randomized to receive either a pneumococcal glycoprotein conjugate vaccine, composed of pneumococcal serotypes 6B, 14, 18C, 19F, and 23F linked to CRM197, or a 23-valent pneumococcal polysaccharide vaccine. Among human immunodeficiency virus (HIV)-uninfected persons, conjugate vaccine elicited significantly higher IgG antibody geometric mean titers (GMTs) than did polysaccharide vaccine for serotypes 6B, 18C, and 23F: IgG GMTs were 9.0 versus 4.8, 23.2 versus 5.9, and 15.3 versus 4.4 micrograms/mL, respectively. In contrast, the two vaccines elicited similar antibody GMTs in HIV-infected persons: GMTs ranged from 1.3 to 10.8 micrograms/mL for all serotypes. Of note, among persons receiving polysaccharide vaccine, antibody GMTs in HIV-uninfected and -infected persons with CD4 lymphocytes > or = 500/microL were similar. These data underscore the importance of controlled clinical evaluations of newer pneumococcal vaccines in all high-risk groups for whom pneumococcal immunization is recommended and highlight the need for early immunization of HIV-infected persons with currently available polysaccharide vaccines.

AIDS-Related Opportunistic Infections↗

Psyllium laxative-induced anaphylaxis, asthma, and rhinitis.

A 69-year-old nurse was evaluated for a recent episode of anaphylaxis that had occurred after psyllium ingestion. She had experienced recurrent rhinitis and asthma related to psyllium exposure for the past 15 years. The diagnosis of psyllium hypersensitivity was established by a positive psyllium puncture skin test, an elevated psyllium-specific IgE level in serum, and a confirmatory soluble-antigen competitive inhibition test. The patient was symptomatic for several years, and this diagnosis was not considered until she suffered potentially life-threatening anaphylaxis. Psyllium hypersensitivity may be a more common phenomenon than is currently appreciated by physicians and other health-care providers.

Aged↗