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Biomedical subjects

R G Slavin

Publications and source records attributed to R G Slavin.

At least 55 records · Page 3Linked to original sources

Intranasal fluocortin butyl in patients with perennial rhinitis: a 12-month efficacy and safety study including nasal biopsy.

Fluocortin butyl (FCB) is a recently developed topical intranasal corticosteroid that is inhaled as a powder and has been demonstrated to be well tolerated and to improve symptoms and signs of perennial rhinitis in previous short-term studies. This multicenter, open-label study evaluated the efficacy and safety of FCB during a 12-month treatment period in patients with perennial rhinitis. Treatment was initiated with one inhalation of FCB in each nostril three times a day (total dosage, 3 mg/day). In subsequent months, one third of the patients was maintained at the dosage of 3 mg/day, one third at a lower dosage of 2 mg/day, and the remaining one third of the patients at a larger dosage of 4 to 8 mg/day. Of 109 patients enrolled in the study, 90 patients (82.6%) completed all 12 months of treatment. Symptom and sign scores decreased significantly (p less than 0.001) at the 2-month evaluation compared to scores at baseline, and the improvement was maintained throughout the 12-month study period. After 12 months, greater than 80% of the patients had substantial control of symptoms. Specimens of nasal biopsies, performed at the beginning and end of treatment, revealed a decrease in eosinophils and other cellular infiltrates, a slight tendency of an increase in mast cell counts, and a trend toward normalization of the nasal mucosa. There were few adverse effects. Mean plasma cortisol levels were normal before and after corticotropin stimulation at baseline and after 12 months of FCB therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Intranasal↗

Characterization of eosinophils in a continuous ambulatory peritoneal dialysis patient with eosinophilic peritonitis.

A continuous ambulatory peritoneal dialysis patient developed eosinophilic peritonitis and was followed for 7 months. After 1 month, the peritonitis resolved, with a concomitant drop in percentage of hypodense eosinophils (Eos) recovered from peritoneal dialysate (PD) as well as a drop in fluid major basic protein levels. Blood eosinophil differential percentages were low, but the percentage of hypodense Eos in the blood tended to be relatively increased. Stool samples showed no evidence of parasitic infection, and epicutaneous skin tests were negative. Leukotriene C4 levels remained relatively constant as did white blood cell counts. Flow cytometric analysis of lymphocytes and granulocytes from PD and blood revealed high levels of CD23-positive lymphocytes.

Adult↗

T- and B-cell dysregulation of IgE synthesis in cystic fibrosis patients with allergic bronchopulmonary aspergillosis.

Since Aspergillus fumigatus (Af)-specific and polyclonal serum IgE levels are characteristically elevated in patients with allergic bronchopulmonary aspergillosis (ABPA), we evaluated in vitro regulation of IgE synthesis in cystic fibrosis (CF) patients with ABPA. We studied 11 CF patients with ABPA, 37 patients with positive Af prick skin tests and/or IgG precipitating antibodies (ST/PPT+), and 35 patients with no humoral or skin responses to Aspergillus (ST/PPT-). Mean serum IgE concentration was significantly elevated in CF subjects with ABPA compared to ST/PPT+ and ST/PPT- patients, 2866 vs 303 and 61 IU/ml, respectively (P less than 0.01). In vitro studies demonstrated that ABPA patients' B cells spontaneously synthesized significantly increased amounts of IgE compared to ST/PPT positive and negative subjects, 1980 vs 220 and 13 pg/ml, respectively (P less than 0.01). In addition, preformed B-cell-associated IgE was also significantly elevated in ABPA subjects (P less than 0.01), indicating prior in vivo activation. Supernatant cultures of Af-stimulated T cells from ABPA subjects significantly induced allogeneic B-cell IgE synthesis compared to ST/PPT positive and negative CF subjects, 206 vs 13 and 4 pg/ml, respectively (P less than 0.01). Thus T cells stimulated with Aspergillus antigens secrete cytokines that induce B-cell IgE synthesis in ABPA subjects. B-cell IgE hyperactivity is manifested by in vivo and in vitro increased IgE concentrations. Analyses of T-cell regulation and B-cell IgE synthesis distinguish CF subjects with ABPA from Aspergillus sensitive non-ABPA subjects.

Aspergillosis, Allergic Bronchopulmonary↗

Serum immunoglobulins E and G anti-Aspergillus fumigatus antibody in patients with cystic fibrosis who have allergic bronchopulmonary aspergillosis.

Patients with cystic fibrosis frequently have pulmonary colonization with Aspergillus fumigatus (Af) and develop anti-Af immunoglobulin E (IgE) and IgG antibodies. The diagnosis of allergic bronchopulmonary aspergillosis in subjects with cystic fibrosis is difficult because of the high incidence of Af colonization, with development of humoral antibody responses. In this study, we sequentially measured serum anti-Af IgE (Af-E) and IgG (Af-G) antibodies by ELISA in subjects with cystic fibrosis. In subjects with cystic fibrosis who have allergic bronchopulmonary aspergillosis, Af-E and Af-G antibodies were significantly increased when compared with other groups of patients with cystic fibrosis who had positive skin tests or precipitins to Af (or both) (p less than 0.01, p less than 0.01, respectively). In addition, increased Af-E and Af-G levels were sometimes seen in other groups, especially subjects with cystic fibrosis who had positive Af skin tests or precipitin tests, two of whom later developed criteria diagnostic of allergic bronchopulmonary aspergillosis. Thus, serum Af-E and Af-G levels were quantitatively increased in subjects with cystic fibrosis who had allergic bronchopulmonary aspergillosis and thus adjunctive data in diagnosis. However, it also suggested that subclinical pulmonary inflammation may also occur.

Adolescent↗

Positive Multi-Test reactions do not cause false positive reactions at adjacent sites.

To answer the question of whether proximity of Multi-Test skin test sites causes false positive reactions, 50 subjects with prior 4+ skin test responses were retested with antigens and ten additional subjects were tested with histamine (1.8 mg/mL). No positive readings occurred at any of the replicate saline control sites adjacent to 3+ or 4+ allergen sites or to 3+ histamine reactions.

Adolescent↗

In vitro T cell responses in patients with cystic fibrosis and allergic bronchopulmonary aspergillosis.

Allergic bronchopulmonary aspergillosis (ABPA) occurs as a complication in patients with cystic fibrosis (CF). Previous studies of the immunopathogenesis of ABPA have indicated that B cells (IgG and IgE antibodies to Aspergillus fumigatus), T cells, and eosinophils are components of the disease. To evaluate T-cell regulation, we examined in vitro immune responses in seven patients with CF and ABPA compared with subjects who had a positive reaction to an A. fumigatus (Af) prick skin test, an IgG precipitating antibody test, or both (ST/PPT), and with subjects with CF who had negative prick skin test results and precipitating antibodies to Af (Af negative). Analyses of T-cell phenotypes revealed that patients with CF and ABPA compared with patients with CF who had ST/PPT positive and Af negative results had slightly increased percentages of T-helper cells, 50.1% versus 43.0% (p not significant) and 42.2 (p less than 0.025), respectively, but comparable percentages and numbers of T-suppressor cells. Serum IgE concentrations were significantly increased in subjects with CF and ABPA versus both subjects who had ST/PPT-positive and Af-negative results, 2916 versus 281 and 73 IU/ml (p less than 0.001 and less than 0.001, respectively). In addition, B cells from patients with CF and ABPA had significantly increased in vitro preformed IgE (p less than 0.01) and increased spontaneous de novo IgE spontaneous synthesis compared with cells from subjects who had ST/PPT positive and Af-negative results (p less than 0.01 and less than 0.01), indicating prior in vivo activation.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigens, Fungal↗

Sinusitis in adults and its relation to allergic rhinitis, asthma, and nasal polyps.

Sinusitis, an infection of the paranasal sinuses, has been linked to allergic rhinitis, asthma, and nasal polyps. Sinusitis is a common complication of allergic rhinitis, which can lead to inflammation of the sinus mucosa, obstruction of the sinus opening or ostium, and generally favorable conditions for bacterial growth. Sinusitis can trigger asthma. Stimulated nerves in an infected sinus may result in parasympathetic stimulation to the bronchial tree and in smooth muscle contraction. Sinusitis may be a cause of nasal polyps, which are common when sinusitis complicates allergic rhinitis and even more common in nonallergic rhinitis. Treatment of sinusitis strives to eliminate infection and promote drainage. Ampicillin or amoxicillin is the antibiotic of choice. All patients with sinusitis should be treated with antibiotic to encourage drainage. Fluids, expectorants, and decongestants, both oral and topical, should be used. As many as half of patients with sinusitis also have marked rhinitis (either allergic or nonallergic), nasal polyps, or swollen, edematous mucosa; these patients should also receive topical steroids, such as flunisolide. Flunisolide promotes drainage and aeration by decreasing inflammation, swelling, and the influx of white blood cells. Persistent sinusitis may need to be treated surgically.

Adult↗

Sinusitis in adults.

Sinusitis in adults is being increasingly recognized as a common clinical entity. To protect against infection of the paranasal sinuses, patent ostia, mucous of the proper viscosity, and actively beating cilia are necessary. The superior placement of the maxillary ostia predisposes to maxillary sinusitis. A number of surgical procedures are available to treat chronic sinusitis that does not respond to appropriate medical therapy. The recently introduced technique of endoscopic surgery of the sinuses shows great promise. The association of sinusitis and bronchial asthma is well recognized, but causality is more difficult to prove. There is suggestive evidence in both children and adults that medical or surgical treatment of underlying sinusitis frequently improves the asthmatic state, but well-designed prospective studies are needed that control or measure relevant variables.

Adult↗

A pathologic study of allergic bronchopulmonary aspergillosis.

A lung biopsy specimen was obtained from a 10-year-old boy with cystic fibrosis and allergic bronchopulmonary aspergillosis. Light microscopy revealed a marked inflammatory process that was largely bronchocentric. Infiltrating cells included lymphocytes, plasma cells, monocytes, and numerous eosinophils. Elastin layers were intact in blood vessels and markedly disrupted in bronchioles. By immunofluorescent, major basic protein was demonstrated in eosinophils, was freely deposited outside of eosinophils, especially in the interlobular septum, and was taken up by macrophages. A number of lymphocytes stained positively for IgE. Through an immunoperoxidase stain, septate hyphae of Aspergillus were clearly observed in the lung parenchyma. A significant increase in interleukin-2 positive-staining T cells was observed with an approximate 2:1 ratio of helper to suppressor cells. The use of newer immunohistologic techniques has enabled us to gain additional insights into the pathogenesis of allergic bronchopulmonary aspergillosis.

Aspergillosis, Allergic Bronchopulmonary↗

Decreased T helper cell function in patients with cystic fibrosis.

T cell immune function was further evaluated in cystic fibrosis (CF) patients. CF patients, regardless of severity of pulmonary disease or colonization with Pseudomonas aeruginosa, had lower percentages of T helper cells (p less than 0.01) and decreased T helper function as demonstrated by diminished T help for control B cell pokeweed mitogen-stimulated IgG (p less than 0.01) and IgM (p less than 0.01) synthesis. Increased T suppressor function, measured by co-culture with control B and T cells, was noted in only 25% of CF patients. CF patients' T cells exhibited decreased allogeneic T cell cytotoxicity compared to normal controls (p less than 0.01). This study extends previous studies demonstrating decreased T cell functions in CF patients and indicates a specific decrease in T helper function.

Adolescent↗

Participation of cell-mediated immunity in allergic bronchopulmonary aspergillosis.

While IgE and IgG antibodies are thought to play important pathogenetic roles in allergic bronchopulmonary aspergillosis (ABA), the microscopic lung picture would implicate cell-mediated immunity. Patients with ABA do not manifest delayed skin test reaction to Aspergillus fumigatus (AF). This has been attributed to inhibition of lymphokines by histamine locally released as a result of the immediate skin test reaction. We tested 5 ABA patients for delayed hypersensitivity to AF. An attempt was made to ablate the immediate skin test reaction to determine if a delayed reaction might be unmasked. At concentrations of AF previously shown to produce marked immediate skin test reactions, the combination of cimetidine by mouth and chlorpheniramine mixed with AF in the skin test syringe completely eliminated the immediate skin test reaction in all 5 patients. In no case did a delayed reaction appear. Eight ABA patients showed in vitro lymphocyte stimulation responses to AF that were comparable to those of asthmatics and rhinitics with positive immediate skin test reactions to AF and no clinical evidence of ABA. It thus appears that 'peripheral' cell-mediated immune responses, namely delayed skin reactivity and peripheral blood lymphocyte proliferation to AF, are not present in ABA.

Administration, Oral↗