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Biomedical subjects

J Dolovich

Publications and source records attributed to J Dolovich.

At least 73 records · Page 4Linked to original sources
PubMed1993

Airway inflammation in symptomatic and asymptomatic children with methacholine hyperresponsiveness.

A definition of asthma includes symptoms due to reversible airflow limitation and airway hyperresponsiveness. Characteristically, there is also airway inflammation. In children with methacholine airway hyperresponsiveness but no asthma symptoms, we examined whether there were features of asthmatic airway inflammation. Forty one children, aged 11-16 yrs, were studied. Thirteen asymptomatic children with methacholine airway hyperresponsiveness (provocative concentration producing a 20% fall in forced expiratory volume in one second (PC20) geometric mean of 3.35 (range 1.08-7.81) mg.ml-1) were compared with 13 currently symptomatic asthmatics with a similar PC20 of 1.91 (0.42-6.5) mg.ml-1 and 13 normal children with a normal PC20 of 52.4 (17.6 to > 64) mg.ml-1. Breathlessness experienced during a methacholine test was recognized to have occurred previously in 7 out of 13 asymptomatic children and all symptomatic children. Asymptomatic children had significantly more airway responses to hyperventilation with cold dry air (4 out of 13) than normal children (0 out of 13) but less than symptomatic children (11 out of 15). Sputum induced with hypertonic saline contained lower eosinophil counts in the asymptomatic children (median (interquartile range) 0.20 (0.59)%) than in the symptomatic children (1.70 (9.45)%), and not different from the normal children (0.15 (0.61)%). Budesonide, 400 micrograms b.i.d. improved respiratory symptoms, forced expiratory volume in one second (FEV1) and methacholine PC20 in symptomatic children, but this effect did not reach statistical significance in asymptomatic children. We conclude that symptomatic children are more likely to have evidence of asthmatic inflammation than asymptomatic children and this probably explains the symptom difference.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗
PubMed1993

Occupational asthma due to zinc.

We describe a subject who developed asthma symptoms 2 yrs after being employed at a plant where metals were galvanized in heated zinc. The subject was not atopic. Baseline spirometry was normal three months after he left work but there was mild bronchial hyperresponsiveness to methacholine. Monitoring of forced expiratory volume in one second (FEV1) during a day at work showed a maximum fall in FEV1 of 24% at the end of the day and an increase in bronchial responsiveness on the following day. Environmental monitoring revealed that zinc and iron were present in the working environment at concentrations that were lower than the "threshold limit value-short term exposure level" (TLV-STEL) standards. Positive immediate skin tests to zinc sulphate at concentrations of 1 and 10 mg.ml-1 were obtained, although no specific immunoglobulin E (IgE) antibodies to zinc could be found. Skin tests with copper, chromium and cobalt were negative. Specific inhalation challenges were performed, having the subject inhale a solution of zinc sulphate at a 10 mg.ml-1 concentration for 6 min. An immediate reaction was elicited (maximum fall in FEV1 of 23%). We conclude that zinc can cause occupational asthma.

Asthma↗
PubMed1992

Generalized allergic reactions during anesthesia.

Twenty-eight adults with a history of a generalized allergic reaction during anesthesia were investigated. The reactions were systemic in 23 adults, urticaria/angioedema in four, and bronchial obstruction in one adult. The study population and an additional 35 subjects with a history of use of thiopental during anesthesia but without reactions were investigated by methods including thiopental skin test, succinylcholine skin test, and IgE RAST for antibodies to thiopental, succinylcholine, or latex. Among the 28 patients with reactions, 17 had positive thiopental skin tests; 14/28 reactors and 1/35 of the control group had an IgE thiopental RAST value greater than 2 SD above the mean for control sera from ragweed-allergic subjects. The one control subject with a positive thiopental RAST also was the only control subject with a positive thiopental skin test. IgE succinylcholine RAST was negative in all 23 reactor sera tested. The IgE latex RAST was strongly positive in one reactor. In conclusion, evidence of allergy, particularly allergy to thiopental as a possible basis for the reactions, was obtained in greater than 50% of the patients who were investigated. No allergy to succinylcholine was found.

Adolescent↗
PubMed1992

A research method to induce and examine a mild exacerbation of asthma by withdrawal of inhaled corticosteroid.

This study evaluated a research method to examine an exacerbation of asthma induced by corticosteroid withdrawal. Ten non-smoking adult asthmatics who were stable on treatment with inhaled steroid underwent a graded reduction of the daily dose by 200 micrograms at weekly intervals until an exacerbation of symptoms occurred. A daily symptom, peak expiratory flow rate (PEF) and medication diary was kept. Weekly clinic visits were used to assess symptoms, spirometry, methacholine airway responsiveness (expressed as the provocative concentration to cause a fall in FEV1 of 20%, PC20), circulating eosinophils, basophils and their progenitors (Eo/B-CFU), and sputum inflammatory cells. The laboratory tests were performed blind to the clinical details. Each subject developed an exacerbation of symptoms, on average at 16 (7-26) days after the onset of steroid reduction. This was accompanied by a deterioration in each of the objective measures. There was a fall in FEV1 by 320 ml (s.e.m. 9.5) and in PC20 from 0.8 to 0.43 mg/ml. Circulating eosinophils rose from 114 (24) x 10(3)/ml to 227 (50) x 10(3)/ml and Eo/B-CFU rose from 31 (5.6) to 44 (11.3)/10(6) cells. Sputum developed in five subjects and contained 36 (5.2)% eosinophils and 1.98 (0.21)% metachromatic cells (mast cells or basophils). The symptom diary and weekly questionnaire were demonstrated to be valid and responsive to change. A deterioration indicated by the daily symptom score preceded changes in PEF. Treatment by an increase in steroid was followed by reversal of each of the changes.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗
PubMed1992

Use of induced sputum cell counts to investigate airway inflammation in asthma.

BACKGROUND: Airway inflammation is considered to be important in asthma but is relatively inaccessible to study. Less invasive methods of obtaining sputum from patients unable to produce it spontaneously should provide a useful investigational tool in asthma. METHODS: A method to induce sputum with inhaled hypertonic saline was modified for use in 17 asthmatic patients and 17 normal subjects who could not produce sputum spontaneously. The success rate and safety of the method, the reproducibility of cell counts, and differences in cell counts between the asthmatic and normal groups were examined. Hypertonic saline solution 3-5% was inhaled for up to 30 minutes after inhalation of salbutamol. Subjects were asked to expectorate sputum every five minutes. The quality of the sample was scored on the volume of plugs and the extent of salivary contamination. Plugs from the lower respiratory tract were selected for a total cell count and for differential cell counts of eosinophils and metachromatic cells (mast cells and basophils) in direct smears. RESULTS: Adequate samples from the lower respiratory tract were obtained in 76% of first attempts. The mean fall in the forced expiratory volume in one second (FEV1) during inhalation of saline was 5.3% and the maximum fall 20%. Eosinophil and metachromatic cell counts were reproducible (reliability coefficient 0.8 and 0.7 respectively). When compared with sputum from normal subjects sputum from asthmatic patients contained a significantly higher proportion of eosinophils (mean 18.5% (SE 3.8%) v 1.9% (0.6%)) and metachromatic cells (0.50% (0.18%) v 0.039% (0.014%)). In the asthmatic group the differential eosinophil count correlated with the baseline FEV1. CONCLUSION: Induced sputum is capable of detecting differences in cell counts between normal and asthmatic subjects and merits further development as a potential means of assessing airway inflammation in asthma.

Adolescent↗
PubMed1992

Changes in the cellular profile of induced sputum after allergen-induced asthmatic responses.

Allergen inhalation causes airway inflammation and an increase in histamine airway responsiveness. We have used cell counts in sputum induced by hypertonic saline aerosol to assess airway inflammation before and 32 h after asthmatic responses to allergen. Twelve asthmatic subjects (mean age, 27.4 yr; range, 20-38 yr) had an inhalation test with D. farinae, ragweed pollen, or cat extract. All of them developed an early response with a fall in FEV1, of 24.8% (SD, 6.3%); nine of 12 had a definite late response (fall in FEV1 greater than or equal to 15%), and 10 of 12 had an increase in airway responsiveness to histamine at 32 h (PC20 reduced by greater than twofold). Sputum was induced by hypertonic saline after the histamine test, before and 32 h after the allergen challenge, at the same time of day. The quality of the sample was scored according to visual inspection and inverted microscopy and by salivary contamination. Plugs arising from the lower respiratory tract were selected for further evaluation. Differential cell counts of eosinophils (Eo) and metachromatic cells (MCC) (mast cell and basophils) were obtained from direct smears, blind to the clinical procedures. The mean fall in FEV1 after hypertonic saline was 6.4% (range, zero to 28%). The sputum samples were adequate in 79.5% of attempts. Eo and MCC increased significantly from 3.8 (4.4) to 18.2 (22.8)% (p = 0.01) and from 0.05 (0.17) to 0.25 (0.76)% (p = 0.04), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Formoterol compared with beclomethasone and placebo on allergen-induced asthmatic responses.

Formoterol is a new long-acting beta 2-agonist. We compared the protective effect of 24 micrograms formoterol with 200 micrograms beclomethasone and placebo on inhaled allergen-induced asthmatic responses in mild stable asthmatic subjects. We measured airflow rates, histamine airway responsiveness, cell counts from sputum and peripheral blood, and markers of lymphocyte and eosinophil activation. Adjustments were made for the confounding effect of bronchodilatation produced by formoterol in comparisons using a control inhalation of normal saline. Formoterol caused bronchodilation and inhibition of histamine airway responsiveness for at least 24 h. It completely inhibited the early asthmatic responses when beclomethasone had no effect. Control comparisons of the effect of formoterol and beclomethasone on the allergen-induced late asthmatic response and increase in histamine responsiveness showed each to be equally effective but not to inhibit the responses completely. Formoterol caused bronchodilation in addition to preventing bronchoconstriction. Both drugs inhibited the rise in serum eosinophil cationic protein 24 h after allergen, but neither inhibited the allergen-induced increases in sputum or blood eosinophils or CD25+ lymphocytes. These results suggest that formoterol modifies allergen-induced airway responses through functional antagonism rather than the inhibition of inflammatory cell infiltration.

Adult↗
PubMed1992

Histochemical and immunohistochemical characteristics of mast cells in nasal polyps.

In surgically excised nasal polyps, most epithelial mast cells were formalin sensitive, chloroacetate esterase (CAE) negative, and chymase negative. Thus, this represents a population of mast cells not identified by staining for CAE. On the other hand, most stromal mast cells were formalin resistant and CAE positive, and although there was some polyp-to-polyp variability in their content of neutral protease, most of these cells were positive for both tryptase and chymase. The percentage of metachromatic cells in the epithelium and the number of metachromatic cells per unit area of polyp tissue did not correlate with an index of allergy skin test reactivity or the serum IgE concentration. The percentage of mast cells surrounded by pericellular tryptase, suggesting activation/degranulation, was significantly higher in the stroma than in the epithelium. The findings demonstrate differences between the stroma and the epithelium in phenotype and state of activation of mast cells; these are postulated to be due to distinct microenvironmental factors that affect mast cells at these sites.

Acetates↗
PubMed1992

Eosinophils in chronically inflamed human upper airway tissues express transforming growth factor beta 1 gene (TGF beta 1).

Transforming growth factor beta (TGF beta) is a multifunctional protein which has been suggested to play a central role in the pathogenesis of chronic inflammation and fibrosis. Nasal polyposis is a condition affecting the upper airways characterized by the presence of chronic inflammation and varying degrees of fibrosis. To examine the potential role of TGF beta in the pathogenesis of this condition, we investigated gene expression and cytokine production in nasal polyp tissues as well as in the normal nasal mucosa. By Northern blot analysis using a porcine TGF beta 1 cDNA probe, we detected TGF beta 1-specific mRNA in nasal polyp tissues, as well as in the tissue from a patient with allergic rhinitis, but not in the normal nasal mucosa. By the combination of tissue section staining with chromotrope 2R with in situ hybridization using the same TGF beta 1 probe, we found that approximately 50% of the eosinophils infiltrating the polyp tissue express the TGF beta 1 gene. In addition, immunohistochemical localization of TGF beta 1 was detected associated with extracellular matrix as well as in cells in the stroma. These results suggest that in nasal polyposis where eosinophils are the most prevalent inflammatory cell, TGF beta 1 synthesized by these cells may contribute to the structural abnormalities such as stromal fibrosis and basement membrane thickening which characterize this disease.

Chronic Disease↗
PubMed1991

The spectrum of IgE-mediated responses to latex.

A spectrum of IgE-mediated allergic responses to latex is presented in this report of 14 patients, including health care workers, sensitized by exposure to latex gloves. Symptoms often occurred immediately after exposure to latex, and manifestations varied according to the route of latex antigen presentation. Skin exposure usually caused contact urticaria. Exposure to latex in the air elicited allergic rhinitis, conjunctivitis, and asthma. Systemic effects from latex occurred intraoperatively due to the surgeon's latex gloves. Anaphylactic shock included the above symptoms with the addition of tachycardia and hypotension. All patients had positive latex skin tests. Serum IgE antibody to latex was found with a latex radioallergosorbent test in all but one tested patient. Physicians should be aware that latex allergy can present as anaphylaxis during surgery, barium enema, or dental work. Latex skin tests are a satisfactory method of diagnosis. Nonlatex gloves are available and are tolerated by affected people.

Adolescent↗
PubMed1991

Synergistic effects of nerve growth factor and granulocyte-macrophage colony-stimulating factor on human basophilic cell differentiation.

We have recently shown that nerve growth factor (NGF) promotes human granulopoiesis, specifically augmenting basophilic cell differentiation observed in methylcellulose hematopoietic colony assays of human peripheral blood. Because the NGF effect was seen in the presence of conditioned medium derived from a human T-cell line (Mo-CM) containing granulocyte-macrophage colony-stimulating factor (GM-CSF), we examined interactions of purified NGF and recombinant human GM-CSF (rhGM-CSF) on granulocyte growth and differentiation. rhGM-CSF stimulated a dose-dependent increase in methylcellulose colony growth at concentrations between 0.1 U/mL and 10 U/mL, and in the presence of NGF at 500 ng/mL this effect was enhanced. The number of basophilic cell colony-forming units (CFU-Baso) and histamine-positive colonies increased synergistically when NGF was added to rhGM-CSF. Furthermore, because Mo-CM acts with sodium butyrate to promote basophilic differentiation of alkaline-passaged myeloid leukemia cells, HL-60, we also examined the interaction of NGF and Mo-CM or rhGM-CSF using this assay. In the presence of NGF, Mo-CM at concentrations of 0.5% to 20% vol/vol, and rhGM-CSF at concentrations of 0.1 U/mL to 100 U/mL synergistically increased histamine production by butyrate-induced, alkaline-passaged HL-60 cells; this was associated with the appearance of metachromatic, tryptase-negative, IgE receptor-positive cells. The effects of rhGM-CSF or Mo-CM were completely abrogated by a specific anti-rhGM-CSF neutralizing antibody in methylcellulose, with or without NGF; the NGF synergy with rhGM-CSF in the HL-60 assay was also inhibited by either anti-rhGM-CSF or anti-NGF antibody. These studies support the notion that differentiation in the basophilic lineage may be enhanced by NGF acting to increase the number of GM-CSF-responsive basophilic cell progenitors.

Basophils↗
PubMed1991

Intraoperative anaphylaxis: an association with latex sensitivity.

Latex products have recently been identified as the cause of severe intraoperative anaphylactic reactions. We have identified a group of pediatric patients who appear to be at increased risk for such reactions. Fifteen patients with either spina bifida or congenital urologic abnormalities experienced 19 intraoperative anaphylactic reactions. All patients had frequent previous exposures to rubber materials since infancy as part of their management and/or investigative procedures. Seven of 15 patients had a previous history of local skin reactions to rubber. Only four patients were atopic. All patients had undergone multiple (two of 26) operative procedures before their reactions, the onset of which ranged from 40 to 290 minutes after induction of anesthesia. The reactions varied in intensity from urticaria to severe cardiorespiratory collapse. All these patients subsequently had positive allergy skin tests and positive RAST to latex antigen. We conclude that this group is at risk when they are exposed to latex intraoperatively as a result of frequent past exposure to these materials. Allergic evaluation for latex allergy may assist in the preoperative evaluation of similar patients. In sensitized patients, appropriate prophylactic measures, particularly the avoidance of latex, is required.

Adolescent↗