Diagnostic dilemma. Vocal cord dysfunction.
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Adult↗
Biomedical subjects
P A Greenberger
Publications and source records attributed to P A Greenberger.
T cell proliferation and cytokine secretion to T cell epitopes of Asp f 2 in ABPA patients.
The pathogenesis of allergic bronchopulmonary aspergillosis (ABPA) involves specific cytokines secreted by lymphocytes in response to Aspergillus fumigatus (Af) allergens. To gain information about the lymphoproliferative response and cytokine production against a major Af allergen, Asp f 2, we studied Asp-f-2-specific T cell clones (TCCs) from ABPA patients. TCCs were stimulated with rAsp f 2, its deletion mutants, and synthetic peptides to identify the T cell epitope(s) and to understand cytokine production. PBMCs from four of five ABPA patients showed proliferation in response to Asp f 2. Three TCCs from one patient showed higher IL-5 secretion compared to IL-4 and IFN-gamma. Two TCCs from the second patient showed a mixed Th1/Th2 response, as evidenced by production of IL-4, IL-5, and IFN-gamma. An epitope from the N-terminal region of Asp f 2 induced only IL-5 secretion. High IL-5 secretion might explain the marked eosinophilia observed in ABPA patients.
Amino Acid Sequence↗
Immunologic studies in presumed amniotic fluid embolism.
OBJECTIVE: To evaluate the potential role of immunologic mechanisms that involve mast cell degranulation (anaphylaxis) or complement activation in the mechanism of amniotic fluid embolism. METHODS: This study was a case series of nine women with presumed amniotic fluid embolism and a control group of 22 women who had normal labor. Women were from community and tertiary referral hospitals in Japan and the United States. Main outcome measures were maternal peripartum complement levels (C3 and C4), serum levels of tryptase, urinary histamine concentrations, and serum levels of a fetal antigen (sialyl Tn). RESULTS: Serum tryptase and urinary histamine measurements were negative in women with amniotic fluid embolism; seven of nine had elevated levels of fetal antigen. All eight who had serum available for testing had abnormally low levels of complement. Mean C3 level of 44.0 mg/dL and C4 level of 10.7 mg/dL were significantly lower than corresponding postpartum control values of 117.3 mg/dL and 29.4 mg/dL (P =.018 for C3, P =.012 for C4). Postpartum C3 and C4 levels decreased by 8% and 5%, respectively, compared with intrapartum values (P =.003 for C3, P =.021 for C4) but were still within normal range. CONCLUSION: Serologic findings suggest a role for complement activation in the mechanism of amniotic fluid embolism. Laboratory data from this series did not implicate mast cell degranulation (anaphylaxis) in the pathophysiology of the disease.
Antigens, Tumor-Associated, Carbohydrate↗
Bee pollen-induced anaphylactic reaction in an unknowingly sensitized subject.
BACKGROUND: The food supplement bee pollen has been previously found to cause anaphylactic reactions. It has been proposed as useful for "everything from bronchitis to hemorrhoids." OBJECTIVE: This study describes an atopic patient who experienced a non-life-threatening anaphylactic reaction upon her initial ingestion of bee pollen. Microscopic examination of the pollen sample and ELISA inhibition assays were performed. RESULTS: The patient had a 7 mm/28 mm wheal/erythema reaction to bee pollen at 1 mg/mL concentration. Bee pollen caused 52% inhibition of IgE binding to short ragweed and 55% to ryegrass. Microscopic analysis revealed ragweed, Alternaria, Cladosporium, honeysuckle (Lonicera sp), privet shrub (Ligustrum sp), and vetch (Vicia sativa). CONCLUSIONS: An unknowingly sensitized atopic patient experienced an anaphylactic reaction after ingestion of a small quantity of bee pollen that contained pollens and fungi. Previously administered allergen immunotherapy that had reduced rhinitis symptoms did not prevent this allergic reaction.
Allergens↗
Cloning and expression of Aspergillus fumigatus allergen Asp f 16 mediating both humoral and cell-mediated immunity in allergic bronchopulmonary aspergillosis (ABPA).
BACKGROUND: Aspergillus fumigatus, a ubiquitous fungus, is responsible for a number of lung disorders in atopic and non-atopic individuals. Standardized, pure, and relevant allergens are desirable for reliable immunodiagnosis of the disease and to understand the structural and functional properties of these allergens and the role they play in causing ABPA. OBJECTIVE: Molecular cloning and characterization of a relevant allergen from A. fumigatus cDNA library. MATERIALS AND METHODS: A cDNA library was constructed from 96 h old mycelium of A. fumigatus using lambda ZAP expression vector. A novel gene encoding an A. fumigatus allergen was identified by screening the library with sera from ABPA patients. The gene was cloned and the allergen over-expressed in Escherichia coli. This recombinant allergen, Asp f 16, was evaluated in ELISA and Western blots using sera from patients and normal subjects and peripheral blood mononuclear cells (PBMC) for antigen-induced stimulation. RESULTS: Seventy percent of the patients with ABPA demonstrated high levels of serum IgE antibodies to Asp f 16, a 43-kDa protein, whereas patients with allergic asthma, Aspergillus skin test-positive asthmatics without clinical evidence of ABPA, and normal controls failed to show Asp f 16-specific IgE binding by ELISA. The deduced amino acid sequences of Asp f 16 showed extensive sequence homology to 30.6-kDa Asp f 9 at the N-terminal region of the protein. PBMC from the majority of patients with ABPA exhibited significant proliferation with the recombinant Asp f 16 allergen. CONCLUSION: Specific humoral and cell-mediated immune responses of Af-sensitized patients against Asp f 16 suggest its usefulness in the immunodiagnosis of hypersensitivity diseases due to Af and understanding the pathophysiology of ABPA.
Allergens↗
The incidence of antimicrobial allergies in hospitalized patients: implications regarding prescribing patterns and emerging bacterial resistance.
BACKGROUND: The development of antimicrobial guidelines is one way in which institutions attempt to control emerging resistance, but the real challenge falls on promoting and ensuring adherence to these guidelines. Investigating reasons for the prescribing of alternative antimicrobial agents outside of these guidelines is crucial for modifying practices that may adversely impact institutional antimicrobial goals. METHODS: Retrospective cross-referencing of computerized pharmacy printouts and concurrent manual medical record review. RESULTS: Approximately 25% (470/1893) of the patients requiring antimicrobial therapy reported an allergy to at least 1 antimicrobial agent. The most commonly reported antimicrobial allergy was penicillin (295/1893 [15.6%]). Eighty-five patients (18.1%) reported having an allergy to 2 or more antimicrobial agents. Only 4% (27/601) of the reported antimicrobial allergies contained documentation as to the nature of the specific allergic reactions, while a manual medical record review revealed that 32% (23/73) of the antimicrobial allergies contained documentation of the specific allergic reaction. Ninety-eight (39. 7%) of 247 patients reporting an allergy only to penicillin and/or cephalosporin received vancomycin in comparison with 247 (17.4%) of 1423 patients without any antimicrobial allergies (P<.001). Similarly, 53 (21.5%) of 247 patients with reported penicillin and/or cephalosporin allergies received levofloxacin compared with 114 (8.0%) of 1423 patients without any antimicrobial allergy (P<. 001). CONCLUSION: The incidence of penicillin allergy at our institution exceeds population averages. This finding, in combination with limited documentation of drug allergies, appears to lead to the prescribing of alternative antimicrobial agents that do not fit into institutional antimicrobial guidelines and, in some instances, may put the patient at risk for infection and/or colonization with resistant organisms. Use of these alternative agents may adversely impact the ability to manage emerging antimicrobial resistance.
Anti-Bacterial Agents↗
Antibody binding of deletion mutants of Asp f 2, the major Aspergillus fumigatus allergen.
Asp f 2, a 268 amino acid major allergen from Aspergillus fumigatus (Af) demonstrated nine linear IgE binding regions. It is not known whether any of these linear epitopes are also conformatory epitopes. Hence, we constructed deletion mutants of Asp f 2 devoid of one or more epitopes, and the IgE binding of these proteins with sera from patients with ABPA was compared with the full-length Asp f 2 expressed in E. coli and Pichia. The Pichia expressed protein reacted weakly with IgE, but strongly with IgG of ABPA sera compared to E. coli expressed Asp f 2. Weak IgE binding only was seen when the C-terminal or N-terminal was deleted, while depletion of both ends negated all reactivity. The monoclonal antibody IL-B8 and IgE and IgG of ABPA sera bound significantly to the Asp f 2 E-4 fragment indicating that the major B-cell epitope is located at the N-terminal end of Asp f 2.
Allergens↗
Potentially fatal asthma and asthma deaths: knowledge is greater but implementation appears problematic.
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Asthma↗
Selected recombinant Aspergillus fumigatus allergens bind specifically to IgE in ABPA.
BACKGROUND: Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity lung disease resulting from exposure to Aspergillus fumigatus allergens. Patients with ABPA show elevated Aspergillus-specific serum IgE, a major criterion used in the diagnosis of the disease. Crude culture filtrate and mycelial antigens have been used widely to demonstrate IgE antibody to Aspergillus in the sera of patients. While these antigens have been useful in the diagnosis of ABPA, occasionally they present inconsistency in their reactivity and lack of specificity. Although in recent years, a number of purified A. fumigatus allergens have been produced by molecular cloning, no attempt was made to evaluate them systematically. OBJECTIVE: To evaluate the recombinant proteins from A. fumigatus for their IgE antibody binding, we studied sera from ABPA patients and controls by antigen specific enzyme linked immunosorbent assay (ELISA). METHODS: Recombinant Aspergillus allergens Asp f 1, f 2, f 3, f 4, and f 6 were studied for their specific binding to IgE in the sera of ABPA patients, A. fumigatus skin prick test positive asthmatics, and normal controls from the USA and Switzerland. The sera were blinded and studied by ELISA in two different laboratories. RESULTS: All the recombinant allergens showed IgE antibody binding with sera from patients with ABPA, whereas only fewer asthmatics and normal sera showed significant binding. The three selected recombinant allergens together reacted with all the ABPA patients studied. CONCLUSIONS: The results demonstrate that Asp f 2, f 4, and f 6 can be used in the serodiagnosis of ABPA, while IgE antibody binding to Asp f 1 and f 3 was not specific.
Allergens↗
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↗
Allergic emergencies in the physician's office.
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Allergens↗
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↗
Sensitization to Aspergillus species in the congenital neutrophil disorders chronic granulomatous disease and hyper-IgE syndrome.
BACKGROUND: Hyper-IgE syndrome (HIE) and chronic granulomatous disease (CGD) are congenital immunodeficiency diseases with increased susceptibility to bacterial and fungal infections. Both carry significant morbidity and mortality rates because of invasive infections by Aspergillus species. We encountered 2 patients, one with HIE and one with CGD, in whom detection of sensitization to Aspergillus species preceded the diagnosis of immunodeficiency. With high-dose systemic corticosteroids for allergic bronchopulmonary aspergillosis (ABPA), an inflammatory disorder caused by sensitization to Aspergillus species, pulmonary abscesses developed in the patient with HIE, and the patient with CGD succumbed to an overwhelming Aspergillus species-induced pneumonia. OBJECTIVE: We sought to assess the prevalence of sensitization to Aspergillus fumigatus and the presence of diagnostic criteria for ABPA in patients with CGD and HIE. METHODS: We measured A fumigatus-specific serum IgE, IgG, and precipitating antibodies as indicators for A fumigatus sensitization in the sera of 18 patients with neutrophil disorders (7 with HIE and 11 with CGD). Hospital records were reviewed for the presence of other diagnostic criteria for ABPA (asthma, elevated total serum IgE concentration, and radiographic abnormalities). RESULTS: Twelve (67%) of 18 patients were sensitized to A fumigatus, as evidenced by precipitating A fumigatus-specific antibodies. Six (33%) of 18 patients had serologic evidence of ABPA. Five of those 6 patients had radiologic abnormalities consistent with a diagnosis of ABPA. One patient with HIE also had asthma, thus fulfilling minimal essential criteria for concurrent ABPA. CONCLUSIONS: Patients with HIE syndrome and CGD have a high incidence of sensitization to Aspergillus species. A clinical picture indistinguishable from ABPA may coexist or emerge in patients with CGD or HIE and create a major management dilemma because systemic corticosteroids may accelerate tissue damage and invasive fungal infections. It is important to distinguish individuals with congenital neutrophil disorders from uncomplicated classic ABPA.
Adult↗
Allergic bronchopulmonary aspergillosis with multiple Streptococcus pneumoniae lung abscesses: an unusual initial case presentation.
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Abscess↗
Bupropion hydrochloride induced serum sickness-like reaction.
BACKGROUND: Bupropion hydrochloride is used frequently in the treatment of depression and in smoking cessation therapy. METHODS: We report a case of bupropion hydrochloride induced serum sickness-like reaction. RESULTS: There was complete resolution of symptoms on discontinuing bupropion and instituting therapy with prednisone and antihistamines. CONCLUSION: This case is seemingly the first report of a serum sickness-like reaction to bupropion hydrochloride.
Adult↗
Clindamycin hypersensitivity appears to be rare.
BACKGROUND: A patient developed a generalized confluent erythematous papular rash after a single injection of clindamycin preoperatively. The literature from two small studies suggested a 10% incidence of cutaneous eruptions to clindamycin which seemed too high. OBJECTIVE: Describe a patient with clindamycin hypersensitivity and determine the incidence of hospital-wide adverse drug reactions from clindamycin from 1995-1997. METHODS: At a tertiary care center, utilizing the Department of Pharmacy records, the incidence of adverse drug reactions was determined with (1) voluntary physician reporting, (2) Health Information Management chart reviews and adverse drug reaction coding, and (3) chart reviews by the Pharmacy and Therapeutics Committee of adverse drug reactions. RESULTS: (I) A 50-year-old patient developed a generalized raised, erythematous rash that worsened over 3.5 days until hydrocortisone was administered. Immediate skin tests with clindamycin were negative. (2) From 3,896 administrations of clindamycin from April 1995 to October 1997, 14 (0.47%) adverse drug reactions occurred but 7 were confounded by other medications also being administered. CONCLUSION: (1) Adverse drug reactions to clindamycin are much lower than reported 25 years ago with an incidence < 1%. (2) A patient who previously had experienced facial edema and a generalized rash after receiving clindamycin and a cephalosporin 6 years ago and who was considered allergic to cephalosporins, was found to be clindamycin allergic when she received a preoperative dose of clindamycin.
Antibiotic Prophylaxis↗