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Biomedical subjects

J Dolovich

Publications and source records attributed to J Dolovich.

At least 127 records · Page 7Linked to original sources

Cellular characteristics of sputum from patients with asthma and chronic bronchitis.

The reproducibility of sputum cell counts was examined and the cell counts in patients with asthma were compared with those in patients with chronic bronchitis. Three groups of subjects were studied. Sputum from eight patients with chronic asthma and with sputum production were studied to determine the reproducibility of sputum cell counts. The findings in 10 non-smokers with asthma uncomplicated by other airway disease examined at the time of an exacerbation with sputum (group 2) were compared with those from eight smokers with chronic cough and sputum but no features of asthma (group 3). Sputum plugs were selected by microscopy to ensure their origin from the lower respiratory tract. A total cell count was performed on a trypsinised suspension, and differential and metachromatic cell counts were performed on undiluted plugs. The within specimen and test-retest reproducibility of these measurements was high (reliability coefficient, R, = 0.99 and 0.89). The sputum of the asthmatic patients was characterised by eosinophilia (69%, range 46-92%) and the presence of formaldehyde blockable metachromatic cells (1.5%, range 0.6-2.8%). In comparison, the sputum of the patients with chronic bronchitis had few eosinophils (0.5%) or metachromatic cells (0.14%); the dominant cell type was the macrophage (83%). It is concluded that sputum cell counts are reproducible in the short term, the inflammation of asthma is characterised by eosinophilia and metachromatic cells in sputum, and sputum may provide a useful source of cells for investigating the cellular characteristics of airway inflammation.

Adult↗

Factors influencing basophilic differentiation of HL-60 cells.

Lineage-specific hematopoietins apparently act in concert with multipotent factors in an orderly sequence of growth and differentiation. We have used the human acute promyelocytic leukemia cell line HL-60 to examine basophilic differentiation, using radioenzymatic assay of histamine content as an end point. Recombinant human interleukin 1 (rhIL-1), rhIL-2, rhIL-4, and recombinant human alpha and gamma interferons did not stimulate basophilic differentiation either in the presence or absence of sodium butyrate, an important cofactor for induction of differentiation. In contrast, rhG-CSF (granulocyte colony-stimulating factor), rhGM (granulocyte-macrophage) CSF, rhIL-3, rhIL-5, nerve growth factor, conditioned medium (CM) from the hairy T cell leukemic line Mo, and nasal polyp epithelial CM stimulated significant increases in histamine content in HL-60 cells at day 5 in vitro. GM-CSF did not account for all of the basophilic differentiating activity in Mo-CM. The data suggest that a unique, lineage-specific, basophilic cell differentiation factor is produced by T cells and point to the possible diagnostic and therapeutic relevance of in situ hematopoietic mechanisms in human respiratory disease.

Biological Factors↗

Allergic rhinitis nasal mucosal conditioned medium stimulates growth and differentiation of basophil/mast cell and eosinophil progenitors from atopic blood.

In previous studies of human nasal polyps and nasal mucosa from subjects with allergic rhinitis, we have demonstrated hematopoietic progenitors, measured as colony-forming units (CFU) in culture, and colony-stimulating activities for basophil/mast cells (BMC) and basophil/eosinophils (Eo). In the present study, conditioned medium (CM) from short-term cultures of nasal mucosal scrapings of subjects with allergic rhinitis are compared with those from normal subjects for colony-stimulating activities, with BMC and Eo CFU in methylcellulose assays of peripheral blood from atopic (N = 6) or nonatopic (N = 6) individuals. CM derived from cultures of nasal mucosal scrapings from subjects with allergic rhinitis stimulated a significantly greater number of BMC/Eo CFU from the peripheral blood of atopic (out-of-season and ragweed-allergic) subjects than from peripheral blood of nonatopic subjects in a series of matched-control experiments (20.6 +/- 4.6 versus 1.9 +/- 0.8; p less than 0.002); in contrast, nasal mucosal CM from normal control subjects did not stimulate an increase in these CFU in peripheral blood from atopic compared to nonatopic subjects. These studies further support the hypothesis that in situ hematopoietic mechanisms are operative in allergic inflammatory reactions and suggest the presence of cells in affected (allergic) epithelium that are "activated" to produce large amounts of BMC and Eo growth and differentiation factors.

Basophils↗

Occupational asthma from reactivity to an alkaline hydrolysis derivative of gluten.

A 29-year-old female subject had been working for 13 years in a company producing biscuits. She was exposed intermittently to an alkaline hydrolysis wheat gluten derivative (AHGD) that was incorporated into marshmallows. Five years before being referred, she started reporting rhinoconjunctivitis and asthmatic symptoms immediately after handling AHGD. When she was first assessed, she had avoided contact with AHGD for 1 year, and she was asymptomatic. Normal spirometry and bronchial responsiveness to histamine (provocative concentration causing a 20% fall in FEV1, 22 mg/ml) were obtained. There was a positive allergy skin test to ragweed pollen and to AHGD at 0.01 mg/ml. Skin tests with individual extracts of cereals, including wheat, were negative. Inhalation challenge with AHGD for 15 seconds caused immediate rhinoconjunctivitis and bronchoconstriction (maximum fall of 40% in FEV1 30 minutes after the exposure) with complete recovery 2 hours later. There was no reaction thereafter, and the provocative concentration of histamine causing a 20% fall in FEV1 was not significantly changed (13.1 mg/ml) 9 hours after the challenge. Inhalation challenge with wheat flour containing native gluten for 30 minutes did not cause any symptoms or significant change in FEV1. IgE RAST counts were greater with the AHGD than with gluten and the whole wheat extract; the opposite was generally found with sera from individuals with baker's asthma and wheat food allergy. With the serum of the affected worker, AHGD completely inhibited the corresponding RAST, but gluten did not. With wheat food allergy, AHGD was relatively inactive inhibition of the wheat and gluten RAST, but gluten was effective.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Efficacy of continuous treatment with astemizole (Hismanal) and terfenadine (Seldane) in ragweed pollen-induced rhinoconjunctivitis.

Astemizole (Hismanal; Janssen Pharmaceutica Inc., Mississauga, Ontario, Canada) and terfenadine (Seldane; Merrell Dow Pharmaceuticals [Canada], Inc., Concord, Ontario, Canada) were compared for clinical efficacy in a double-blind randomized trial during the ragweed pollen season. Sixty adults, with a history of ragweed-induced rhinoconjunctivitis, were matched according to sensitivity to ragweed pollen. Half took astemizole, 10 mg/day, and the rest took terfenadine, 60 mg twice daily. Medications were started 1 week before and continued daily until 1 week after the ragweed pollen season (7 weeks). If the trial medication was insufficient to keep symptoms well controlled, a steroid nasal spray and/or eye drops were used in the minimum dose that would ensure symptoms were not troublesome. Subjects completed a diary of nocturnal and daytime nasal and eye symptoms and recorded the amount of concomitant medications used. Astemizole showed greater efficacy than terfenadine in controlling rhinorrhea; in addition, the astemizole group used less nasal spray. Other nasal symptoms, eye symptoms, and use of eye drops were similar in the two groups. Skin test sensitivity to serial dilutions of histamine and ragweed extract was determined 1 and 7 weeks after the start of the trial medication. More tachyphylaxis to histamine was shown by the subjects taking terfenadine, as demonstrated by a larger increase in skin sensitivity over the study period. However, a similar change was not observed for ragweed skin sensitivity. These results suggest that when the medication is started before and continued daily throughout the pollen season, astemizole is more efficacious than terfenadine in controlling nasal symptoms, but there is little difference for eye symptoms.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Isolated late cutaneous skin test response to ampicillin: a distinct entity.

A case presentation describes a young woman with a history of two reactions to ampicillin therapy and a reproducible skin test reaction of intermediate timing that disappeared within 48 hours. The skin test response was to ampicillin only and not to other penicillin-related skin test reagents. Tests for serum IgE and IgG antibody to ampicillin were negative. The histology was that of a mononuclear and neutrophilic cellular infiltrate with neutrophil margination in the vessels. There was no immunoglobulin, complement, or fibrin deposition. The skin test reaction began and ended earlier than would be expected for a classic delayed hypersensitivity reaction. It is considered to be an isolated late cutaneous response but cannot yet be designated a late cutaneous allergic response. Reactants characteristic of an Arthus reaction were not present, and no alternative immunologic basis was confirmed.

Adult↗

Early/late response model: implications for control of asthma and chronic cough in children.

The observed airways inflammation in asthma and chronic cough supports the conclusions of clinical trials, namely, that our treatment regimens should emphasize inhaled cromolyn. The need for bronchodilators as backup therapy is real but represents testimony to the fact that in some cases it has not been possible to entirely eliminate the inflammation and the consequent airways hyperresponsiveness.

Asthma↗

Human nasal polyp epithelial basophil/mast cell and eosinophil colony-stimulating activity. The effect is T-cell-dependent.

We have previously reported highly potent basophil/mast cell (BMC) and basophil/eosinophil (Eo) colony-stimulating activities (CSA) in conditioned medium derived from cultured human nasal polyp epithelial scrapings (NP-CM). We now have examined the involvement of peripheral blood T-cells in the NP-CM stimulation of colony-forming units (cfu) from the blood of atopic and nonatopic subjects. Because the number of BMC- and Eo-cfu was significantly higher in cultures of peripheral blood from subjects with out-of-season ragweed allergic rhinitis than from control subjects (23.8 +/- 4.1 versus 9.0 +/- 2.4, p less than 0.01), we asked whether the observed colony stimulation could be a T-cell-dependent effect. Indeed, peripheral blood target cells consisting of a reconstituted mixture of T-cells and T-cell-depleted peripheral blood mononuclear cells (non-T-cells) yielded a significantly higher number of colonies in the presence of NP-CM than the non-T-cells alone. NP-CM did not stimulate colony formation by isolated T-cells. These observations point to interactions among nasal epithelial growth and differentiation factors, blood-borne progenitors and T-cells in the local accumulation of basophils, mast cells, and eosinophils in nasal polyps.

Basophils↗

Intranasal nedocromil sodium in the treatment of ragweed-allergic rhinitis.

Nedocromil sodium (NS), a new pyranoquinoline dicarboxylic acid derivative, reported to be effective against both mucosal and connective tissue-type mast cells, was studied in ragweed-allergic rhinitis (RAR). Thirty-six patients with RAR were studied in an 8-week, double-blind, placebo-controlled trial. Stratification was based on prick skin test sensitivity and severity of signs and symptoms of previous RAR. NS (1% solution) in a dose of 0.13 ml of nasal spray was administered to each nostril, a minimum twice daily. Concomitant medications were limited to ingested terfenadine, ocular cromolyn, and inhaled medications. Symptoms and medications were noted daily. Active-treatment and placebo-treatment groups were comparable. There were less symptoms of runny nose and itchy eyes in the active-treatment group (p less than 0.05) and also less antihistamine, p less than 0.004. Patients in the active-treatment group were more likely to conclude that symptoms were improved by the nasal spray (p less than 0.01). No side effects were reported. This study indicates that NS is effective and well tolerated in RAR.

Adult↗

Laminar flow air cleaner bed attachment: a controlled trial.

Thirteen house dust mite-allergic young asthmatics were entered into a double-blind, crossover clinical trial to compare "in use" with "non-use" of a laminar flow air cleaner bed attachment. The study design encouraged maintenance of symptom control by adjustment of the dose of medications used. There was a significant reduction in the amount of medications required by the patients during the trial period that the air cleaner was in use. Histamine airway responsiveness was significantly decreased for a group of eight of the subjects tested at the end of a 3-month open trial.

Adolescent↗

Prevention of chymopapain anaphylaxis by screening chemonucleolysis candidates with cutaneous chymopapain testing.

With chymopapain at a concentration of 10 mg/ml, the authors skin tested 540 chemonucleolysis candidates; six were positive, and 534 were negative. None of the positive patients received therapeutic injections of chymopapain. There were no instances of unequivocal anaphylaxis to chymopapain in the patients with negative skin tests treated with chymopapain. When this 0% incidence of systemic reactions in skin test negative patients is compared with the historical rate of 1%, this difference is statistically significant (p less than 0.05). Restriction of chymopapain treatment to patients with negative prick tests can reduce the incidence of systemic reactions.

Anaphylaxis↗

Control of the hypersecretion of vasomotor rhinitis by topical ipratropium bromide.

A randomized, double-blind, placebo-controlled trial of ipratropium bromide nasal spray was performed with 25 patients with vasomotor rhinitis. Criteria for selection of patients were (1) clear watery nasal discharge more than 1 hour each day, (2) absent or mild nasal obstruction, (3) no known allergic cause, and (4) no satisfactory response to previous alternative medications. Ipratropium bromide, two sprays (20 micrograms per spray) in each nasal cavity four times daily, for 3 weeks, produced a major reduction in nasal discharge severity and duration (p less than 0.00005 for daytime reduction in both). There was a decreased daily use of nasal tissues (p = 0.0017). At the end of the trial, 21 patients preferred the drug, two preferred placebo, one had no preference, and one patient dropped out for a reason unrelated to symptoms or treatment. This drug preference in favor of active medication was statistically significant at the 0.01 level. Local mild side effects were reported in 21/25 (84%) with ipratropium bromide and 8/25 (32%) with placebo (p = 0.0004). Pulse and blood pressure were not affected. In an ensuing 1-year open trial in which the frequency of use of ipratropium bromide nasal spray was selected by the subjects, the dosage chosen was considerably lower than that used in the controlled trial. There were seven dropouts caused by insufficient benefit or local side effects. Seventeen subjects continued the use of ipratropium bromide for 1 year and reported good results and no side effects. Topical nasal ipratropium bromide is highly effective in the control of the rhinorrhea of vasomotor rhinitis. Drug dosage is a major determinant of local nasal side effects.

Administration, Topical↗