Hypersensitivity to IFN-alpha.
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Antibodies↗
Biomedical subjects
K E Harris
Publications and source records attributed to K E Harris.
Lymphocyte subsets and activation markers in patients with acute episodes of idiopathic anaphylaxis.
BACKGROUND: Idiopathic anaphylaxis (IA), a type of anaphylaxis in which no external allergen can be identified, is a corticosteroid-responsive disease, that suggests that it may have an immunologic pathogenesis. OBJECTIVE: The objective of this study is to compare patients with acute episodes of IA with normals, patients with chronic idiopathic urticaria, and patients with IA in remission relative to lymphocyte subsets and activation markers. METHODS: This is a prospective cohort study of 38 adults: 5 normals, 4 idiopathic urticaria, 11 IA patients in remission, 9 IA patients with acute attacks who had not yet received prednisone, and 9 IA patients who had received prednisone. The main outcome measures were lymphocyte subset and activation markers determined by two and three color flow cytometry (CD2, CD3, CD4, CD5, CD8, CD16, CD19, CD23, CD25, CD56, and HLA-DR). RESULTS: Comparing patients with acute IA with those in remission, the only significant difference was that the acute IA patients had a significantly higher percentage of CD3+HLA-DR+ cells. Normals had a significantly lower percentage of CD3+ HLA-DR+ cells than all other groups. Patients with acute IA on prednisone as well as IA patients in remission had a significantly higher percentage of CD 19+ CD23+ cells than normals. CONCLUSIONS: These results suggest that there are more activated T cells in patients with acute episodes of IA than in patients in remission. Perhaps, these activated T cells have a role in the pathogenesis of IA.
Anaphylaxis↗
Hypersensitivity pneumonitis resulting from community exposure to Canada goose droppings: when an external environmental antigen becomes an indoor environmental antigen.
BACKGROUND: In the past, hypersensitivity pneumonitis has been attributed to occupational, agricultural, or home environmental exposure. OBJECTIVE: This report describes the first case of hypersensitivity pneumonitis due to community exposure to droppings from Canada geese migrating through a suburban environment. METHOD: Clinical and serologic information was used in making the diagnosis of hypersensitivity pneumonitis. RESULTS: Serologic analysis demonstrated precipitating antibodies against goose droppings and against an extract made from washings from a filter taken from the patient's office. These studies also showed that the antigens in the office filter were goose dropping antigens. CONCLUSION: Hypersensitivity pneumonitis can result from exposure to goose dropping antigens in the community that enter buildings through ventilation systems. This represents a new form of an old disease.
Air Pollution, Indoor↗
Multicenter, double-blind, placebo-controlled, multiple-challenge evaluation of reported reactions to monosodium glutamate.
BACKGROUND: The frequency of reactions reported to occur after the consumption of monosodium glutamate (MSG) is the subject of controversy. OBJECTIVE: We conducted a multicenter, multiphase, double-blind, placebo-controlled study with a crossover design to evaluate reactions reportedly caused by MSG. METHODS: In 3 of 4 protocols (A, B, and C), MSG was administered without food. A positive response was scored if the subject reported 2 or more symptoms from a list of 10 symptoms reported to occur after ingestion of MSG-containing foods within 2 hours. In protocol A 130 self-selected reportedly MSG-reactive volunteers were challenged with 5 g of MSG and with placebo on separate days (days 1 and 2). Of the 86 subjects who reacted to MSG, placebo, or both in protocol A, 69 completed protocol B to determine whether the response was consistent and dose dependent. To further examine the consistency and reproducibility of reactions to MSG, 12 of the 19 subjects who responded to 5 g of MSG but not to placebo in both protocols A and B were given, in protocol C, 2 challenges, each consisting of 5 g of MSG versus placebo. RESULTS: Of 130 subjects in protocol A, 50 (38. 5%) responded to MSG only, 17 (13.1%) responded to placebo only (P <. 05), and 19 (14.6%) responded to both. Challenge with increasing doses of MSG in protocol B was associated with increased response rates. Only half (n = 19) of 37 subjects who reacted to 5 g of MSG but not placebo in protocol A reacted similarly in protocol B, suggesting inconsistency in the response. Two of the 19 subjects responded in both challenges to MSG but not placebo in protocol C; however, their symptoms were not reproducible in protocols A through C. These 2 subjects were challenged in protocol D 3 times with placebo and 3 times with 5 g of MSG in the presence of food. Both responded to only one of the MSG challenges in protocol D. CONCLUSION: The results suggest that large doses of MSG given without food may elicit more symptoms than a placebo in individuals who believe that they react adversely to MSG. However, neither persistent nor serious effects from MSG ingestion are observed, and the responses were not consistent on retesting.
Adult↗
Review of alleged reaction to monosodium glutamate and outcome of a multicenter double-blind placebo-controlled study.
Monosodium glutamate (MSG) has a long history of use in foods as a flavor enhancer. In the United States, the Food and Drug Administration has classified MSG as generally recognized as safe (GRAS). Nevertheless, there is an ongoing debate exists concerning whether MSG causes any of the alleged reactions. A complex of symptoms after ingestion of a Chinese meal was first described in 1968. MSG was suggested to trigger these symptoms, which were referred to collectively as Chinese Restaurant Syndrome. Numerous reports, most of them anecdotal, were published after the original observation. Since then, clinical studies have been performed by many groups, with varying degrees of rigor in experimental design ranging from uncontrolled open challenges to double-blind, placebo controlled (DBPC) studies. Challenges in subjects who reported adverse reactions to MSG have included relatively few subjects and have failed to show significant reactions to MSG. Results of surveys and of clinical challenges with MSG in the general population reveal no evidence of untoward effects. We recently conducted a multicenter DBPC challenge study in 130 subjects (the largest to date) to analyze the response of subjects who report symptoms from ingesting MSG. The results suggest that large doses of MSG given without food may elicit more symptoms than a placebo in individuals who believe that they react adversely to MSG. However, the frequency of the responses was low and the responses reported were inconsistent and were not reproducible. The responses were not observed when MSG was given with food.
Animals↗
Allergic bronchopulmonary aspergillosis.
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Aspergillosis, Allergic Bronchopulmonary↗
Combination therapy with tirofiban and enoxaparin in acute coronary syndromes.
BACKGROUND: Tirofiban, an intravenous glycoprotein IIb/IIIa antagonist, and enoxaparin, a low molecular weight heparin, have each been shown to be effective at reducing cardiac ischemic events compared to unfractionated heparin alone in separate trials of patients with unstable angina and non-Q-wave myocardial infarction. The combination of these agents may offer further therapeutic benefit. MATERIALS AND METHODS: Fifty-five patients with non-Q-wave myocardial infarction were randomized to receive double-blind treatment with tirofiban (0.1 microgram/kg/min i.v.) for 48-108 h coadministered with either enoxaparin (1 mg/kg sc q 12 h) (n=26) or unfractionated heparin (i.v. adjusted to activated partial-thromboplastin time) (n=27) to evaluate pharmacokinetics, pharmacodynamics, and safety. The primary objective of the study was to investigate the effect of unfractionated heparin versus enoxaparin on the plasma clearance of tirofiban. RESULTS: Coadministration of tirofiban and enoxaparin was generally well tolerated. Plasma clearance of tirofiban was 176.7+/-59.8 and 187.5+/-81.8 ml/min, respectively, for enoxaparin and unfractionated heparin-treated patients (P=NS). The mean difference was well within the prespecified criterion for comparability. Administration of tirofiban with enoxaparin vs. unfractionated heparin resulted in lesser variability and a trend towards greater inhibition of platelet aggregation using 5 microM adenosine phosphate agonist. More patients achieved target inhibition of platelet aggregation >70% in the tirofiban and enoxaparin group (84% vs. 65%, P=0.19). Median bleeding time was 21 min for tirofiban and enoxaparin vs. > or =30 min for tirofiban and unfractionated heparin (P=NS). For a given level of inhibition of platelet aggregation, bleeding time was less prolonged with tirofiban and enoxaparin than tirofiban and unfractionated heparin (adjusted mean bleeding time 19.6 vs. 24.9 min, P=0.02). Tirofiban plasma concentration and clearance were comparable whether coadministered with enoxaparin or unfractionated heparin. There were no major or minor bleeding events in either group by the TIMI criteria. INTERPRETATION: The more consistent inhibition of platelet aggregation and lower adjusted bleeding time of tirofiban and enoxaparin vs. tirofiban and unfractionated heparin support the therapeutic potential of combining these two agents. These data from the first clinical report of coadministration of a glycoprotein IIb/IIIa receptor antagonist and a low molecular weight heparin are consistent with prior data which show differential pharmacodynamic effects of enoxaparin and unfractionated heparin on platelet aggregation.
Angina, Unstable↗
Concurrent administration of inactivated hepatitis A vaccine with immune globulin in healthy adults.
301 healthy adult volunteers were randomized to one of three treatment groups: inactivated hepatitis A vaccine alone; inactivated hepatitis A vaccine with immune globulin (Ig) concurrently; or Ig alone. The first two treatment groups received a second dose of hepatitis A vaccine at week 24. Anti-HAV was measured 4, 8, 12, 24 and 28 weeks after the primary immunization. When comparing subjects receiving inactivated hepatitis A vaccine alone to those receiving vaccine and Ig, the seropositivity rates were not significantly different at 4, 8, 12 and 28 weeks, but at week 24 the seropositivity rate was lower in the group receiving both vaccine and Ig compared to the group receiving vaccine alone (92.0% compared to 97.0%). At weeks 8, 12 and 24 the geometric mean titers (GMTs) were significantly lower for subjects receiving both vaccine and Ig. The GMTs were not significantly different after the second dose of vaccine. At all time points, the lower serum antibody concentrations observed in subjects receiving both inactivated hepatitis A vaccine and Ig were nevertheless substantially higher than the cutoff for assay seropositivity and much higher than after Ig alone; these differences are therefore clinically insignificant.
Adolescent↗
Potential effect of the administration of substance P and allergen therapy on immunoglobulin E-mediated allergic reactions in human subjects.
Previously we observed and reported that immunoglobulin E-mediated (IgE-mediated) allergy in rhesus monkeys was decreased by the administration of substance P (SP) and an allergen. We extended these studies to human subjects, giving SP and 1 allergen to subjects with reactivity to more than 1 allergen, using reactivity to a second allergen as a control. SP and an allergen were initially given by aerosol delivery but subsequently were given by injection. The administration of SP and 1 allergen by aerosol delivery or injection resulted in decreased IgE-mediated reactivity to the allergen administered and also to the control allergen. This result occurred in 7 of 8 human subjects. The 2 initial subjects receiving 8 SP and allergen injections had a sharp reduction in their symptoms of ragweed hay fever lasting for 3 years to date. No significant reactions to the injection of SP occurred. Further controlled human research is necessary on the administration of SP and allergen and the mechanisms of action. Unexpected and serendipitous results first observed in rhesus monkeys and reproduced in allergic human subjects provide a new and potential mechanism for control and perhaps obliteration of common IgE-mediated allergies and even more-serious allergic problems.
Aerosols↗
Rush immunotherapy in a dog with severe ragweed and grass pollen allergy.
BACKGROUND: Forty years of study of naturally occurring IgE-mediated allergy in animals is briefly reviewed. These studies provided models for study of bioactive mediators and innovative pharmacologic therapies for IgE-mediated asthma. OBJECTIVE: Based on our experience with canine allergy we evaluated and treated a dog with severe grass and ragweed allergy whose allergic dermatitis was uncontrolled by H1 blockers and topical corticosteroids. The dog was miserable during the Chicago grass and ragweed pollen seasons. METHODS: Rush immunotherapy was initiated during the ragweed season of 1997. RESULTS: Dramatic improvement was seen which persisted through the grass and ragweed seasons of 1998 after maintenance immunotherapy. CONCLUSION: The case is presented not as a model for canine immunotherapy but as an example of how animal research can be of value to both animals and humans.
Allergens↗
Immunoglobulin E antibody against environmental allergens in subjects with trimellitic anhydride-induced asthma.
The purpose of this study was to assess the relationship between atopy and the development of occupational asthma as a consequence of exposure to trimellitic anhydride (TMA). A case-control study was performed, which comprised 16 employees identified as having TMA-induced asthma and 44 similarly exposed controls. Specific immunoglobulin E measurements in response to cat, dust mite, ryegrass, and ragweed antigens were performed. Fifty-six percent of cases and 29% of controls were found to be atopic (P = 0.098). We demonstrated that there was a trend toward employees with TMA asthma being more atopic than those without TMA asthma. Atopy as an assessment of risk for the development of TMA asthma is unlikely to be useful, although further investigation may be warranted.
Adult↗
Six-month angiographic and clinical follow-up of patients prospectively randomized to receive either tirofiban or placebo during angioplasty in the RESTORE trial. Randomized Efficacy Study of Tirofiban for Outcomes and Restenosis.
OBJECTIVES: This study sought to investigate the effects of tirofiban versus placebo on the incidence of adverse cardiac outcomes and coronary artery restenosis at 6 months. BACKGROUND: Tirofiban is a highly selective, short-acting inhibitor of fibrinogen binding to platelet glycoprotein IIb/IIIa. In a recent clinical study, tirofiban reduced the incidence of adverse cardiovascular events at both 2 and 7 days after coronary angioplasty or directional coronary atherectomy. This reduction persisted but was no longer statistically significant at 30 days. METHODS: The Randomized Efficacy Study of Tirofiban for Outcomes and Restenosis (RESTORE) trial was a randomized, double-blind, placebo-controlled trial of tirofiban in patients undergoing balloon angioplasty or directional atherectomy within 72 h of presentation with either unstable angina pectoris or acute myocardial infarction. All patients received an initial bolus (10 microg/kg body weight over 3 min), followed by a 36-h infusion (0.15 microg/kg per min) of either tirofiban or placebo. RESULTS: At 6 months the composite end point (either death from any cause, new myocardial infarction, bypass surgery for angioplasty failure or recurrent ischemia, repeat target vessel angioplasty or stent insertion for actual or threatened abrupt closure) occurred in 1,070 placebo group patients (27.1%) and 1,071 tirofiban group patients (24.1%, p = 0.11). Analysis of 6-month coronary arteriograms by means of quantitative coronary arteriography showed no significant difference between placebo- and tirofiban-treated patients in either the incidence of a > or =50% diameter stenosis (57% vs. 51%, p = NS), a loss of > or =50% of lumen diameter gained (50% vs. 50%, p = NS) or a loss of > or =0.72 mm of lumen diameter (44% vs. 42%, p = NS). CONCLUSIONS: The 3% absolute reduction in the incidence of the composite end point at 6 months (27.1% placebo vs. 24.1% tirofiban) was similar to that previously reported at 2 days (8.7% vs. 5.4%, p < 0.005), and there does not appear to be any late effect of tirofiban on clinical end points between day 2 and 6 months. Tirofiban did not reduce the incidence of restenosis at 6 months when defined in a number of ways.
Adult↗
Hypersensitivity pneumonitis due to humidifier disease: seek and ye shall find.
STUDY OBJECTIVES: This study reports a classic case of hypersensitivity pneumonitis (HP) with classic histologic changes in lung tissue and the research used to identify the causative antigens. DESIGN: A patient with clinical, radiographic, pulmonary function abnormalities and a lung biopsy consistent with HP had no identifiable antigen exposure. SETTING: Evaluation of the patient's activities provided no suggestion of antigen exposure. Her home was evaluated. It was found that her humidifier ran continually without being cleaned but water was added periodically. MEASUREMENTS: Serologic analysis demonstrated precipitating antibodies against her humidifier water and ten antigens in the hypersensitivity lung disease serologic panel. CONCLUSION: Removal of the humidifier, cleaning of the house, and a course of prednisone resulted in the return of the patient to a normal state.
Aged↗
Malignant and corticosteroid-dependent idiopathic anaphylaxis: successful responses to ketotifen.
BACKGROUND: Malignant idiopathic anaphylaxis refers to the most severe form of idiopathic anaphylaxis where defined episodes of idiopathic anaphylaxis are not controlled when the prednisone is reduced below at least 60 mg every other day or 20 mg daily. Corticosteroid-dependent idiopathic anaphylaxis refers to patients with idiopathic anaphylaxis who require continuous daily or alternate day prednisone at threshold doses for control of idiopathic anaphylaxis. Ketotifen has been reported to help induce remission in some patients with idiopathic anaphylaxis and has steroid sparing effects in other patients with idiopathic anaphylaxis. METHODS: We present five patients, two with malignant idiopathic anaphylaxis and three with corticosteroid-dependent idiopathic anaphylaxis, who responded to the administration of ketotifen. RESULTS: All five patients, while receiving ketotifen, had a reduction or resolution of their episodes of idiopathic anaphylaxis and prednisone was tapered and discontinued. CONCLUSION: Ketotifen is shown to be successful in inducing remission in two patients with malignant idiopathic anaphylaxis and in three additional patients with corticosteroid-dependent idiopathic anaphylaxis. An additional patient with malignant idiopathic anaphylaxis had prednisone stopped after elective hip surgery.
Adrenal Cortex Hormones↗
A bradykinin antagonist inhibits both bradykinin- and the allergen-induced airway response in primates.
Bradykinin is a mediator of bronchoconstriction and may play a role in the development of the asthmatic response after antigen challenge. Our objective was to study the effectiveness of NPC 17731 as a specific bradykinin beta 2-receptor antagonist and as an antagonist of the allergen-induced early phase of asthma. A primate model was used for all studies. Intracutaneous end-point titrations were performed with bradykinin. A shift of the bradykinin end-point titer was seen when NPC 17731 was injected by the intradermal route prior to performing the end-point titration. Using an aerosolized bradykinin or Ascaris suum antigen airway threshold challenge system, inhibition of the bradykinin or Ascaris airway response was evaluated after pretreatment with aerosolized NPC 17731. NPC 17731 proved to be a safe, effective specific bradykinin receptor antagonist in both cutaneous and airway challenges. NPC 17731 was able to inhibit the antigen-induced airway response in the primate. Bradykinin may play a larger role in mediating the early phase of the antigen-induced asthmatic response than previously was appreciated.
Animals↗
Idiopathic anaphylaxis: a series of 335 cases.
BACKGROUND: Idiopathic anaphylaxis is anaphylaxis with no definable etiology and no trigger by exogenous allergens. Initially described in 1978, idiopathic anaphylaxis has been subsequently characterized and treatment protocols have been established. OBJECTIVE: The demographics and course of 335 patients (225 previously reported) treated with prednisone, hydroxyzine, and albuterol are now reported. RESULTS: Ages ranged from 5 to 83 years. There were nine new pediatric patients in this series totaling 14 (4.2%). Atopy was common (48%) with 34 new patients with asthma. The duration of symptoms prior to presentation ranged from three days to 27 years. One hundred thirty-two patients with idiopathic anaphylaxis were available for follow-up. Twenty of these are currently receiving prednisone for control of idiopathic anaphylaxis, seven of them as part of their initial therapy, and ten for control of recurrence of symptoms. Three patients required continuous alternate day prednisone for control of symptoms (corticosteroid-dependent idiopathic anaphylaxis). Of the 335 patients, there were no longer any patients with the diagnosis of malignant idiopathic anaphylaxis defined as requiring prednisone, 20 mg daily, or 60 mg every other day, for control of idiopathic anaphylaxis. Of the six patients previously diagnosed with malignant idiopathic anaphylaxis, five no longer required prednisone and one has a decreased prednisone requirement of 20 mg on alternate days. Hospital visits were significantly reduced by the management regimens. There were no fatalities from idiopathic anaphylaxis in this series. CONCLUSIONS: The incidence of idiopathic anaphylaxis is increasing in our practice with more patients being evaluated each year. During 1104 patient years of observation (the longest period of single patient observation being 24 years), no inciting agent has been found responsible for the anaphylactic symptoms. Prognosis continues to remain good with the majority of patients achieving remission with pharmacotherapy.
Adolescent↗
Total serum IgE in trimellitic anhydride-induced asthma.
The objective of this study was to determine whether total serum IgE levels are elevated in workers with trimellitic anhydride-induced asthma as compared with anhydride-exposed workers without an occupational immunologic syndrome. Sera from 12 highly exposed workers with trimellitic anhydride-induced asthma, and from 31 similarly exposed workers without occupational immunologic disease, were assayed for total immunoglobulin E (IgE) levels by Total IgE II FAST analysis. The mean total IgE levels were 176.74 ng/mL and 34.55 ng/mL respectively. The difference between the two groups was statistically significant, but considerable overlap of IgE levels between groups was seen. In conclusion, although mean total IgE levels are significantly different between TMA-exposed workers with or without occupational asthma, the significant amount of overlap and poor sensitivity of the test preclude the use of this assay in the individual evaluation of these workers.
Adult↗