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Biomedical subjects

R G Hamilton

Publications and source records attributed to R G Hamilton.

At least 37 records · Page 2Linked to original sources

Protamine allergy as a complication of insulin hypersensitivity: A case report.

BACKGROUND: Although most patients receiving insulin produce insulin-specific IgE, significant allergic symptoms develop in very few of them. Patients receiving neutral protamine Hagedorn (NPH) insulin are at increased risk for the development of protamine hypersensitivity. The case of a 19-year-old woman with insulin-dependent diabetes and regular and NPH insulin hypersensitivity is presented. OBJECTIVE: The purpose of this study was to determine whether desensitization to NPH insulin, as well as standard insulin desensitization, could control allergic symptoms in a patient allergic to both NPH and regular insulin. METHODS: The patient required insulin desensitization for severe urticaria, angioedema, and occasional wheezing resulting from her insulin dose. She underwent a standard protocol for insulin desensitization twice in a 2-month period, with persistence in her symptoms. She was found to have high protamine-specific, as well as insulin-specific, IgE levels, and because of her poor response to regular insulin desensitization, she was desensitized to both regular and NPH insulin. RESULTS: Dual desensitization resulted in marked improvement in her symptoms. The patient had recurrence of urticaria and angioedema a year and a half later, at which point the NPH was stopped and she was desensitized to regular insulin. She continued to receive regular insulin 4 times per day over the following 3 years with only occasional hives. CONCLUSION: Patients with insulin allergy may not have complete resolution of their symptoms after standard desensitization, particularly those patients with concomitant protamine allergy. These patients may require protamine/NPH desensitization, an alternative insulin preparation, or both.

Adult↗

A comparison of skin prick tests, intradermal skin tests, and RASTs in the diagnosis of cat allergy.

BACKGROUND: Skin testing and RASTs are the most commonly used methods for the diagnosis of allergy. Questions remain, however, as to the accuracy of these tests, particularly with regard to the role of intradermal skin tests (IDSTs) in the evaluation of respiratory allergy. OBJECTIVE: The purpose of this study was to determine the predictive value of skin prick tests (SPTs), IDSTs, and RASTs in the diagnosis of cat allergy. METHODS: Patients were challenged with a well-characterized cat exposure model after evaluation by history, SPTs, IDSTs (if SPT results were negative), and RASTs. All patients were evaluated with respect to their upper respiratory responses, although only those patients with asthma were included in the analysis of lower airway responses. Challenge results were considered positive if the mean upper respiratory symptom score was 0.5 or more, the mean lower respiratory symptom score was 0.4 or more, or the maximum fall in FEV1 value was 15% or more. RESULTS: One hundred twenty patients were evaluated. SPT values were positive in 81 patients; of the remaining 39 patients, IDST values were positive in 26 patients. RASTs were performed in 89 patients; the values were positive in 45 of 51 patients with a positive SPT value and were negative in all patients with a negative SPT value. When any positive challenge outcome was considered, positive challenge results were seen in 38 of 41 patients with a positive SPT score, in 10 of 39 patients with a negative SPT score, in 6 of 26 patients with a positive IDST score, in 4 of 13 patients with a negative IDST score, in 27 of 27 patients with a positive RAST score, and in 12 of 44 patients with a negative RAST score. CONCLUSION: Although both SPT and RAST values exhibited excellent efficiency in the diagnosis of cat allergy, IDST scores added little to the diagnostic evaluation.

Adult↗

Diagnostic performance of Food and Drug Administration-cleared serologic assays for natural rubber latex-specific IgE antibody. The Multi-Center Latex Skin Testing Study Task Force.

BACKGROUND: In the absence of Food and Drug Administration-approved natural rubber latex skin testing reagents, latex-specific IgE antibody immunoassays are used in the diagnosis of latex allergy. Comparative diagnostic performance of these tests has not been definitively determined. OBJECTIVE: We sought to study the predictive value of available Food and Drug Administration (510K)-cleared latex-specific IgE antibody immunoassays in the diagnosis of latex allergy. METHODS: Subjects (n = 312) were classified as having a positive (n = 117) or a negative (n = 195) latex allergy history (Hx) or having a positive (n = 131) or a negative (n = 181) puncture skin test (PST) response (Greer reagent). The 14 subjects with a negative Hx and a positive PST response had negative responses to glove provocation testing and thus were considered sensitized but asymptomatic. Sera from 22 subjects were split to evaluate intra-assay variation. All 334 coded sera were analyzed for latex-specific IgE antibodies in the Diagnostic Products Corporation microplate AlaSTAT, Hycor HY-TEC EIA System, and Pharmacia-UpJohn CAP System. Variance and diagnostic performance parameters of each test were computed with 95% confidence intervals in relation to the subjects' Hx and PST status. RESULTS: Intra-assay concordance of split sera results was 96.0% for all 3 assays, with coefficients of variation of less than 25% and between-assay coefficients of variation of less than 21%. The diagnostic performance of the CAP and AlaSTAT assays were equivalent in comparison with PST results: sensitivity, CAP 76.3% and ALASTAT 73. 3% and specificity, CAP 96.7% and AlaSTAT 97.2% (P = NS). The HY-TEC assay was more sensitive (91.6%) and less specific (73.3%) than the CAP and AlaSTAT assays (P <.001). From 9% to 25% of the sera were discordant, being positive in at least 1, but not all 3, assays. CONCLUSION: The CAP and AlaSTAT assays produce 24% and 27% of false-negative results, respectively, whereas the HY-TEC produces 27% of false-positive results when compared with the PST.

Antibodies, Anti-Idiotypic↗

Adult onset grape hypersensitivity causing life threatening anaphylaxis.

BACKGROUND: Adverse reactions to foods are encountered much less frequently in adults than in the children. Adult onset hypersensitivity to grapes has not been previously reported. OBJECTIVE: Evaluation of a case of anaphylaxis that occurred as a result of the consumption of white grapes (Vitis vinifera). METHODS AND RESULTS: A 28-year-old woman experienced generalized urticaria, facial/oropharyngeal angioedema, and dizziness after eating a bunch of white grapes. She was treated in an emergency room for anaphylaxis. Previously, she had experienced two similar episodes after eating white grapes. The grape prick skin tests were strongly positive forming a pseudopod type reaction. The total serum IgE was 1918 ng/mL. The grape-specific serum IgE was weakly positive by the modified RAST and negative in the Pharmacia-Upjohn Cap System. CONCLUSION: Hypersensitivity to a commonly consumed fruit such as grapes can develop late in life causing a near-fatal anaphylaxis.

Adult↗

Diagnosis of natural rubber latex allergy: multicenter latex skin testing efficacy study. Multicenter Latex Skin Testing Study Task Force.

BACKGROUND: No characterized diagnostic natural rubber latex skin testing material is licensed for use in the United States. OBJECTIVE: We have conducted a multicenter clinical skin testing study to document the safety and diagnostic sensitivity and specificity of a candidate Hevea brasiliensis nonammoniated latex (NAL) extract. These data are intended to support the licensing of this reagent for the diagnosis of latex allergy in high-risk populations. METHODS: Three hundred twenty-four subjects (304 adults and 20 children) were classified by their clinical history as having latex allergy (LA group, 124 adults and 10 children) or having no latex allergy (NLA group, 180 adults and 10 children). All subjects provided blood samples and then received sequential puncture skin tests (PSTs) at 1, 100, or 1000 microg/mL protein with a bifurcated needle and NAL (Greer Laboratories) from Malaysian Hevea brasiliensis (clone 600) sap. A 2-stage glove provocation test was used to clarify latex allergy status of individuals with positive history/negative PST result and negative history/positive PST result mismatches. RESULTS: Twenty-four subjects (15%) originally designated as having LA on the basis of their initial clinical history were reclassified to the NLA group on the basis of a negative glove provocation test result. Of the 134 subjects with LA, 54 (40%) were highly sensitive to latex, with a positive PST result at 1 microg/mL NAL. The Greer NAL reagent produced a positive PST rate (sensitivity) of 95% and 99% in subjects with LA at 100 microg/mL and 1 mg/mL, respectively. The negative PST rate (specificity) in 190 subjects with a negative history with the NAL extract at 100 microg/mL and 1 mg/mL, was 100% and 96%, respectively. Immediately after the PST, mild systemic reactions (mainly pruritus) were recorded in 16.1 % of the adults in the LA group and 4.4% of the adults in the NLA group. No reactions required treatment with epinephrine. Only mild delayed reactions were observed in 9.6% (LA group) and 2.8% (NLA group) of subjects 24 to 48 hours after PST. Mean wheal and erythema diameters measured in the 10 children in the LA group with spina bifida at 100 microg/mL and 1 mg/mL were similar to those observed in the adults in the LA group, suggesting that children are not at increased risk for systemic reactions compared with adults. CONCLUSIONS: A suggestive clinical history is necessary but not sufficient for a definitive diagnosis of IgE-dependent latex allergy. These data support the safety and diagnostic efficacy of the Greer NAL, skin test reagent at 100 micro/mL and 1 mg/mL for confirmatory PSTs.

Adolescent↗

Ragweed-specific antibodies in bronchoalveolar lavage fluids and serum before and after segmental lung challenge: IgE and IgA associated with eosinophil degranulation.

BACKGROUND: Migration of eosinophils and release of eosinophil degranulation products into bronchoalveolar lavage fluid is a consistent finding in studies of late responses to allergen challenge in the lung. However, the mechanism of eosinophil activation and release of eosinophil products in vivo is unclear. OBJECTIVE: We investigated the hypothesis that antigen-specific IgG, IgA, secretory IgA, or IgE is responsible for the eosinophil activation observed in the late-phase pulmonary reaction. METHODS: Ragweed-specific IgE, IgA, secretory IgA, and IgG were measured by monoclonal antibody-based immunoassays in bronchoalveolar lavage (BAL) fluid and in serum from 19 asthmatic subjects allergic to ragweed and six healthy nonallergic control subjects before and 20 hours after segmental lung challenge with ragweed extract. Eosinophil cationic protein (ECP) was also measured in BAL fluid as a marker of eosinophil activation. RESULTS: Most allergic asthmatic subjects had detectable levels of ragweed-specific IgE, IgA, and IgG in their serum and BAL fluid, whereas normal subjects had ragweed-specific IgA with no ragweed-specific IgE and little ragweed-specific IgG. IgA was the dominant ragweed-specific antibody isotype in BAL fluids. Ragweed-specific sIgA (r[s] = 0.52, p = 0.02) and IgA (r[s] = 0.50, p = 0.03) in BAL fluid after segmental lung challenge were significantly correlated with ECP. Ragweed-specific IgE and IgA in serum also correlated with ECP (r[s] = 0.74, p < 0.001 and r[s] = 0.48, p = 0.04, respectively). CONCLUSIONS: The correlation of allergen-specific IgA and IgE antibody levels with ECP as a marker of eosinophil degranulation suggests an important role for IgE antibodies in allergic pulmonary inflammation and a potential role for antigen-specific IgA in eosinophil degranulation in the lung after antigen challenge.

Adult↗

Humanized antibodies as potential therapeutic drugs.

BACKGROUND: Antibodies have been used therapeutically to treat a variety of clinical conditions. The introduction of monoclonal antibodies and more recently, engineered humanized antibodies has greatly refined and expanded the therapeutic potential of this modality of treatment. LEARNING OBJECTIVES: To reinforce the reader's knowledge of the therapeutic application of antibody in the treatment for different diseases. More specifically, to enhance reader's understanding of basic methods employed in the production and clinical use of humanized antibodies. DATA SOURCE: The MEDLINE database was used to review the humanized antibody related literature. CONCLUSION: Humanized antibodies provide a novel approach for the treatment of a broad range of diseases. Expanded use will depend on improvement in their efficacy (avidity and specificity), demonstration of their safety, and reduction of their immunogenicity.

Animals↗

Factors affecting the retention of dust mite allergen on carpet.

Carpeting is one of the most common and perhaps the most important reservoir of aeroallergens and other components of dust found in residential or commercial settings. This research evaluated factors that affect the retention of dust mite allergens on different types of tufted carpet commonly found in homes and offices. Twenty-six types of carpet were custom manufactured as part of a two-stage factorial experiment using 182 carpet samples. Carpets differed with respect to fiber denier, cross-sectional shape, presence of fluorocarbon treatment, carpet style, pile height, and pile density. The major hypothesis tested was that the amount of allergen-containing dust recovered from vacuum samples of tufted carpet sources was dependent on micro (fiber) or macro (construction) retention characteristics of the carpets. Carpet samples were doped in a uniform and reproducible manner using an allergen-containing reference dust. A standardized vacuum surface sampler was used to recover dust from samples. Allergen was assayed using a standard, monoclonal antibody ELISA. Carpet-surface area and presence of fluorocarbon were found to have the largest effects on retention and recovery of dust and allergen. Specifically, fluorocarbon treatment of fibers, square-hollow fiber shape, high-denier fiber, low-pile height in cut-pile carpets, and low-pile density in loop carpets were significantly associated with increased release and recovery of allergen. Results from this study suggest that carpet type be considered for both allergen avoidance and allergy and asthma risk assessment.

Allergens↗

Prevalence of latex allergy among anesthesiologists: identification of sensitized but asymptomatic individuals.

BACKGROUND: Occupational exposure to natural rubber latex has led to sensitization of health-care workers. However, the prevalence of latex allergy among occupationally exposed workers in American hospitals has not been reproducibly determined. The objectives of the current study were to determine the prevalence of and risk factors for latex sensitization among a cohort of highly exposed health-care workers. METHODS: Participants were 168 of 171 eligible anesthesiologists and nurse anesthetists working in the Department of Anesthesiology and Critical Care Medicine. A clinical questionnaire was administered, and testing was performed using a characterized nonammoniated latex reagent for puncture skin testing, a Food and Drug Administration-approved assay to quantify latex-specific immunoglobulin E antibody in serum, and, when required for clarification, a validated two-stage (contact-inhalation) latex glove provocation procedure. RESULTS: The prevalence of latex allergy with clinical symptoms and latex sensitization without clinical symptoms was 2.4% and 10.1%, respectively. The prevalence of irritant or contact dermatitis was 24%. The risk factors identified for latex sensitization were atopy (odds ratio, 14.1; 95% CI, 1.8-112.1; P = 0.012); history of allergy to selected fruits, such as bananas, avocados, or kiwis (odds ratio, 9.8; 95% CI, 1.6-61.9; P = 0.015); and history of skin symptoms with latex glove use (odds ratio, 4.6; 95% CI, 1.6-13.4; P = 0.006). CONCLUSIONS: The prevalence of latex sensitization among anesthesiologists is high (12.5%). Of these, 10.1% had occult (asymptomatic) latex allergy. Hospital employees may be sensitized to latex even in the absence of perceived latex allergy symptoms. These data support the need to transform the health-care environment into a latex-safe one that minimizes latex exposure to patients and hospital staff.

Adult↗

Immunoglobulin E and eosinophil counts are increased after sepsis in trauma patients.

OBJECTIVES: To determine the time course of plasma immunoglobulin E (IgE) concentration increases after traumatic injury, if increased IgE concentrations were related to clinical events or complications, and if increased peripheral eosinophil counts could be related to trauma, sepsis, or organ-specific complications. DESIGN: Data relating to severity of injury, clinical complications, plasma concentrations of IgE, and peripheral eosinophil counts were prospectively collected. SETTING: Trauma service, tertiary-care medical center. PATIENTS: One hundred adult trauma patients admitted to the intensive care unit. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Plasma IgE concentrations increased in most patients. However, the greatest increases were observed in patients with sepsis (p = .03), renal dysfunction (p = .04), or pneumonia (p = .02). IgE increases were not related to severity or mechanism of injury, allergy history, or age. The day of highest observed IgE concentration was related to the day of onset of sepsis (p = .012, r = .39), and occurred a mean of 3.8 days after sepsis. Most patients had increased peripheral eosinophil counts and eosinophil percentages of white blood cells during their intensive care unit stays. Eosinophil counts were greater in patients with sepsis (p < .0001), severe sepsis (p < .0001), or pneumonia (p < .002). CONCLUSIONS: Increased IgE concentrations and eosinophil counts were found after sepsis and do not appear to be related to the initial injury. Since IgE and eosinophil production are enhanced by interleukin-4 and interleukin-5, respectively, these findings suggest that T-helper lymphocyte type 2 cytokines are activated in response to sepsis after traumatic injury.

Adolescent↗

Repeated aerosol exposure to small doses of allergen. A model for chronic allergic asthma.

To improve our understanding of the pathophysiology of chronic allergic asthma, we mimicked natural allergen exposure by giving tiny doses of dust-mite extract (equivalent to estimated daily exposure in a typical bedroom) in three weekly sessions for 4 wk. Nine mild asthmatic adults who were highly sensitive to dust-mite allergen participated in the study. Serial assessments of bronchial reactivity by methacholine challenge, pulmonary function, symptoms, and bronchodilator requirements were obtained. Seven of nine subjects had a twofold or more (median: 6, range: 2.7 to 25) reduction (p = 0.008) in PC20, after which saline inhalations were substituted for dust-mite extract. Bronchial reactivity returned to normal within 2 to 3 wk after cessation of dust-mite inhalations in all but one subject. Predosing FEV1 dropped 10% over 4 wk of provocation (p = 0.001) and 7 of 9 returned to prestudy level within 2 wk after dosing was stopped. Late-phase responses were seen in 6 of 9 subjects. We conclude that repeated aerosol exposure to dust-mite allergen in doses comparable to natural bedroom exposure is sufficient to adversely affect pulmonary function and bronchial hyperractivity in sensitized individuals. These changes are rapidly reversible. This low-dose provocational strategy provides an attractive model for the experimental study of allergic asthma. Arshad SH, Hamilton RG, Adkinson NF, Jr. Repeated aerosol exposure to small doses of allergen: a model for chronic allergic asthma.

Adolescent↗

Down-regulation of Fc(epsilon)RI expression on human basophils during in vivo treatment of atopic patients with anti-IgE antibody.

Treatment of allergic disease by decreasing circulating IgE with anti-IgE Abs is currently under clinical study. Based on previous unrelated studies, it appeared likely that Fc(epsilon)RI expression on basophils and mast cells might also be regulated by levels of circulating IgE Ab. Therefore, the expression of IgE and Fc(epsilon)RI on human basophils was examined in 15 subjects receiving humanized anti-IgE mAb intravenously. Treatment with the anti-IgE mAb decreased free IgE levels to 1% of pretreatment levels and also resulted in a marked down-regulation of Fc(epsilon)RI on basophils. Median pretreatment densities of Fc(epsilon)RI were approximately 220,000 receptors per basophil and after 3 mo of treatment, the densities had decreased to a median of 8,300 receptors per basophil. Flow cytometric studies, conducted in parallel, showed similar results and also showed in a subset of 3 donors that receptors decreased with a t1/2 of approximately 3 days. The responsiveness of the cells to IgE-mediated stimulation using anti-IgE Ab was marginally decreased (approximately 40%) while the response of the same cells to stimulation with dust mite Ag, Dermatophagoides farinae, was reduced by approximately 90%. One possible explanation for these results is that Fc(epsilon)RI density is directly or indirectly regulated by plasma-free IgE levels.

Adult↗

A controlled trial of immunotherapy for asthma in allergic children.

BACKGROUND: Injections of allergens are widely prescribed for patients with asthma, but little is known about the effectiveness of immunotherapy. METHODS: We conducted a double-blind, placebo-controlled trial of multiple-allergen immunotherapy in 121 allergic children with moderate-to-severe, perennial asthma. The children, who required daily medication for their asthma, were randomly assigned to receive subcutaneous injections of either a mixture of up to seven aeroallergen extracts or a placebo. Maintenance injections were continued for 18 months or longer. Medications were adjusted every two to three weeks on the basis of peak flow rates and symptoms. The principal outcome was the daily medication score. Bronchial sensitivity to methacholine (the concentration provoking a 20 percent decrease in the forced expiratory volume in one second [PC20]) was measured twice yearly. RESULTS: The median medication score declined from 5.4 to 4.9 in the immunotherapy group (P<0.001) and from 5.2 to 5.0 in the placebo group (P<0.001), but there was no significant difference between the groups (P>0.6). The number of days on which oral corticosteroids were used was similar in the two groups. Partial or complete remission of asthma occurred in 31 percent of the immunotherapy group and in 28 percent of the placebo group (P>0.5). There was no difference between the groups in the use of medical care, symptoms, or peak flow rates. The median PC20 increased significantly in both groups, but again with no difference between the two groups. CONCLUSIONS: Immunotherapy with injections of allergens for over two years was of no discernible benefit in allergic children with perennial asthma who were receiving appropriate medical treatment.

Adolescent↗