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Biomedical subjects

R G Slavin

Publications and source records attributed to R G Slavin.

At least 37 records · Page 2Linked to original sources
PubMed1996

Cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations in allergic bronchopulmonary aspergillosis.

The etiology of allergic bronchopulmonary aspergillosis (ABPA) is not well understood. A clinical phenotype resembling the pulmonary disease seen in cystic fibrosis (CF) patients can occur in some individuals with ABPA. Reports of familial occurrence of ABPA and increased incidence in CF patients suggest a possible genetic basis for the disease. To test this possibility, the entire coding region of the cystic fibrosis transmembrane regulator (CFTR) gene was analyzed in 11 individuals who met strict criteria for the diagnosis of ABPA and had normal sweat electrolytes (< or = 40 mmol/liter). One patient carried two CF mutations (deltaF508/R347H), and five were found to carry one CF mutation (four deltaF508; one R117H). The frequency of the deltaF508 mutation in patients with ABPA was significantly higher than in 53 Caucasian patients with chronic bronchitis (P < .0003) and the general population (P < .003). These results suggest that CFTR plays an etiologic role in a subset of ABPA patients.

Adult↗
PubMed1995

Sinusitis in the aged. Optimal management strategies.

Sinusitis is a common medical condition in the elderly; however, the clinical presentation is often subtle and the condition may not be readily diagnosed. The most important clinical clue to the diagnosis of acute sinusitis is the continuation of symptoms after a typical cold has subsided. In chronic sinusitis there is often a distinct lack of symptoms, although most patients will have nasal obstruction and purulent post-nasal drip. On physical examination, the patient with sinusitis will have thick, purulent, green or deep yellow secretions in the nasal passages. The use of radiographic imaging, such as sinus roentgenograms or CT scans, will help confirm the diagnosis. The goal of treatment of sinusitis is eradication of infection with clearance of the infected material from the sinuses. While the use of an appropriate antibiotic is necessary, the use of ancillary therapy is also of utmost importance. Steam and nasal saline, decongestants, topical corticosteroids and mucoevacuants are given in an attempt to reduce nasal obstruction, increase sinus ostia size, promote improved mucociliary function, decrease mucosal inflammation and thin secretions. In selected patients who fail to respond to aggressive medical therapy, functional endoscopic surgery can often provide relief. In patients with poorly controlled asthma, treatment of underlying sinusitis has been shown to dramatically improve the asthmatic state.

Aged↗
PubMed1994

Asp f I CD4+ TH2-like T-cell lines in allergic bronchopulmonary aspergillosis.

Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity lung disease caused by bronchial colonization with Aspergillus fumigatus (Af) characterized by elevated serum total and Af-specific IgE levels and eosinophilia. In order to examine T-cell reactivity to Af antigens, six T-cell lines were established from the peripheral blood of patients with ABPA to Asp f I, an 18 kd protein purified from Af extracts. The Asp f I-specific T-cell lines, analyzed by flow cytometry, were 100% CD3+ CD4+. Lymphoproliferative responses of the T-cell lines were specific for Asp f I stimulation, 28,999 cpm (stimulation index = 12.2), and showed no response to tetanus toxoid stimulation, 2178 cpm (stimulation index = 1.1) (p < 0.001). Furthermore, Asp f I-stimulated lymphoproliferation was inhibited in two experiments by monoclonal anti-interleukin (IL)-4 antibody in a dose-response fashion, 78% and 84% inhibition at 5% concentration of anti-IL-4. In contrast, anti-IL-2 antibody did not inhibit Asp f I-stimulated proliferation. Asp f I-stimulated T-cell lines synthesized predominantly IL-4 (mean, 21.5 ng/ml) after 48 hours of culture, and nondetectable quantities of interferon-gamma and IL-2. In summary, Asp f I-specific T-cell lines established from patients with ABPA were characterized as being CD4+ TH2-like in their cytokine synthesis pattern, and secreted IL-4 behaved in an autocrine fashion, stimulating proliferation.

Allergens↗
PubMed1994

Serum anti-Aspergillus fumigatus antibodies by immunoblot and ELISA in cystic fibrosis with allergic bronchopulmonary aspergillosis.

Allergic bronchopulmonary aspergillosis (ABPA) occurs with a prevalence of 5% to 15% in patients with cystic fibrosis (CF). Because of the frequent colonization with Aspergillus fumigatus (Af) in CF, the causative agent of ABPA, antibody reactivity to Af proteins is frequently observed, which obscures the diagnosis of ABPA. Patients with CF are also categorized according to the presence of positive skin test responses to Af and/or the presence of positive precipitins. In this study we used ELISA and immunoblot assay to detect IgE and IgG anti-Af antibodies in patients with CF and ABPA (n = 13) compared with other groups of patients with CF: those with positive skin test and positive precipitin results (n = 18), those with positive skin test and negative precipitin results (n = 14), those with negative skin test and positive precipitin results (n = 10), and those with negative skin test and negative precipitin results (n = 35). IgE and IgG anti-Af antibodies were significantly elevated in patients with ABPA as determined by both immunoblot assay (p < 0.01) and ELISA (p < 0.01). However, detection of Af antibodies by ELISA was more sensitive in discriminating patients with CF and ABPA from patients with CF who had positive skin test and positive precipitin results but lacked radiographic and clinical evidence of ABPA. In patients with CF and ABPA the immunoblot assays demonstrated a multitude of IgE, IgG, and IgA antibody responses to Af proteins, which ranged in molecular weight from 14 kd to greater than 106 kd. The level of IgE anti-Af antibody to individual proteins decreased during remissions of ABPA.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1993

Henoch-Schoenlein purpura due to streptokinase.

The syndrome of Henoch-Schoenlein purpura developed in a 74-year-old woman after receiving streptokinase as thrombolytic therapy for an acute myocardial infarction. Renal biopsy revealed mesangial hypercellularity with deposits of IgA. Skin biopsy also revealed IgA deposition. Immunological studies showed evidence of sensitization to streptokinase. Elevated IgG, IgA, IgM, and IgE antistreptokinase antibodies were detected in the acute serum. Positive immediate skin reactivity to streptokinase was also present. Serum precipitins to streptokinase disappeared when IgA was removed from the serum. Positive staining with biotinylated streptokinase was seen in the skin in the same pattern of distribution as IgA. These findings strongly support the role of streptokinase and IgA in the pathogenesis of Henoch-Schoenlein purpura in this patient. A control group of streptococcal-infected patients showed no immune response to streptokinase. Another control group of streptokinase-treated patients, who had no untoward reaction, had elevated immunoglobulin classes and precipitins to streptokinase. However, the precipitating antibody was IgG and streptokinase skin tests were negative.

Aged↗
PubMed1993

Occupational asthma to the slime mold Dictyostelium discoideum.

Dictyostelium discoideum is a slime mold that exists in a unicellular amoeboid form under certain nutritional conditions. In this form, it produces unique lysosomal enzymes that are valuable in studying cell-to-cell signaling systems. We report on a research microbiologist who developed rhinoconjunctivitis and asthma after release of D. discoideum from a pressurized canister. Immediate skin test reactivity was demonstrated to whole and lysed organisms. Enzyme-linked immunosorbent assay results revealed IgE antibody against D. discoideum whole organism, lysed organism, and lysosomal enzymes with the strongest response being directed toward lysosomal enzymes. Pulmonary function testing showed a decline in forced expiratory volume in 1 second and forced expiratory flow after modified laboratory exposure to D. discoideum. This case represents the first report of occupational rhinoconjunctivitis and asthma from slime mild.

Adult↗
PubMed1992

Asthma and sinusitis.

Important relationships exist between the upper and lower airways. It is well known that sinusitis and asthma coexist in many patients, and evidence is accumulating that there may be a cause-and-effect relationship, that is, that sinusitis is an important trigger for asthma. Studies in children and adults indicate that appropriate medical and/or surgical therapy of sinusitis frequently leads to improvement in the asthmatic state. Possible mechanisms for this relationship include the eosinophil acting as an effector cell, inflammatory mediators, and a vagal reflex. Further investigations need to examine both prospective studies of the effect of medical therapy for sinusitis on asthma and basic mechanisms relating the upper and lower airways.

Asthma↗
PubMed1992

Increased incidence of stings in venom-sensitive patients.

We compared the histories of 29 venom-sensitive and 28 control subjects who were selected from our venom referral and general allergy clinics respectively. The variables in the study included insect avoidance knowledge, the number of stings during the previous 2 years, insects involved, and time spent out of doors per week. There was no significant difference between the two groups with respect to age. All venom-sensitive patients were well versed in avoidance techniques while only 3 of 28 controls (11%) claimed such knowledge. Venom-sensitive subjects were stung almost ten times more frequently than control subjects. Wasp stings were the most common, followed by yellow jacket, honey bee, and hornet. The venom-sensitive patients also reported spending a greater amount of time outdoors (x 17.4 hours versus x 11.8, P < .05). An analysis of covariance showed that this difference in outdoor exposure was insufficient to account for the disparity in the number of stings. We conclude that other factors such as intrinsic attractants must be responsible for this phenomenon.

Adolescent↗
PubMed1992

Allergic bronchopulmonary mycosis complicating cystic fibrosis.

Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity lung disease caused by bronchial colonization with Aspergillus fumigatus that affects approximately 10% of patients with cystic fibrosis (CF). The diagnosis in CF patients is difficult because the cardinal symptoms of ABPA occur frequently in CF, ie, pulmonary infiltrates and wheezing, as well as the frequent colonization with A fumigatus that leads to humoral reactivity. If left untreated, ABPA leads to bronchiectasis and pulmonary fibrosis. The pathogenesis of ABPA seems to be a prolonged asthmatic late-phase reaction orchestrated by CD4+ Th2-like T cells in response to persistent pulmonary A fumigatus allergen exposure. Thus, polyclonal and A fumigatus-specific IgE antibodies (and IgA and IgG) and blood pulmonary eosinophilia are stimulated by Th2-derived cytokines such as IL-4 and IL-5. In addition, IL-4 would also promote pulmonary transendothelial migration of eosinophils, basophils, and lymphocytes via induction of cell adhesion molecules and their ligands. IgE mast cell interactions would also contribute to the bronchial reactivity and inflammation. Recent advances have begun to identify immunodominant A fumigatus allergens. Evaluation of the quantity of IgE antibodies (and IgA and IgG) and T-cell cytokine responses to specific A fumigatus allergens should aid in the diagnosis and immunopathogenesis of ABPA, especially in CF patients.

Antigens, Fungal↗
PubMed1991

Variability in parameters of allergic bronchopulmonary aspergillosis in patients with cystic fibrosis.

Seventy-nine patients with cystic fibrosis (CF) were evaluated and were followed in a longitudinal, prospective fashion during a 6-year period for the development of immune parameters indicating Aspergillus fumigatus (Af) sensitization and allergic bronchopulmonary aspergillosis (ABPA). Although four patients developed frank ABPA, there was considerable variability in immune parameters in non-ABPA. Twenty-four patients became skin test positive to Af with none losing skin reactivity. Twenty-five patients developed serum precipitins to Af, whereas 12 patients lost their precipitins. Of 15 patients with an elevated total serum IgE of greater than or equal to 2 SD, five demonstrated a marked decline of at least 40%. Three of 16 patients with IgE-Af became negative, whereas eight of 27 patients lost their IgG-Af. None of these patients had received corticosteroid therapy that could have accounted for the findings. Thus, patients with CF frequently lose evidence of Af sensitivity spontaneously without corticosteroid intervention. The diagnosis of ABPA in CF should not be based solely on serology and skin test results, since at any point in time, patients with CF may demonstrate variable responses to Af.

Adolescent↗