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Biomedical subjects

M Topilsky

Publications and source records attributed to M Topilsky.

At least 37 records · Page 2Linked to original sources

Predictive value of response to treatment of T-lymphocyte subpopulations in idiopathic pulmonary fibrosis.

T-cell types are important in maintaining immune homeostasis in the lung and their imbalance may be associated with several diseases. We examined the relationship between bronchoalveolar lavage (BAL) T-cell subset profiles and the clinical course of 46 patients with idiopathic pulmonary fibrosis (IPF). A flow cytometry cell sorter (FACS) was used to analyse the T-cell subsets. Pulmonary function tests (PFT) were performed at baseline and 6-12 months later. Patients were divided into two groups according to their CD4/CD8 ratio: CD4/CD8 >1 (group 1, n=21); and CD4/CD8 <1 (group 2, n=25). A lower percentage of lymphocytes, a higher percentage of CD8/S6F1 cells (cytotoxic T-lymphocytes) and a higher percentage of neutrophils were found in the BAL in group 2 compared to group 1 (11+/-7.5% versus 19+/-13.2%; p=0.024 and 29.8+/-17.6% versus 13.3+/-6.9%; p=0.068, respectively for lymphocytes and cytotoxic T-lymphocytes; and 8+/-11% versus 29+/-27%; p=0.003 for neutrophils). Inversely, in the peripheral blood, the distribution of CD8/S6F1 cells was lower in group 1 than in group 2 (8.3+/-6.9% versus 33.4+/-16.5%; p=0.0048). The patients were followed over a period of 1 yr in order to test whether those findings could determine efficacy of therapy. The baseline transfer factor of the lung for carbon monoxide (TL,CO) capacity in group 1 and group 2 was 59+/-22% and 51+/-21%, respectively (p=0.29), but only in group 1 was the TL,CO capacity improved significantly in response to steroids treatment after 6-12 months. IPF patients with a higher percentage of lymphocytes, a lower percentage of neutrophils, CD4/CD8 >1 and a low percentage of CD8/S6F1 may have a more benign course of disease. These parameters may identify an early stage of reversible disease responsive to therapy. We conclude that these measurements may be a useful tool in monitoring response to treatment in patients with idiopathic pulmonary fibrosis.

Bronchoalveolar Lavage Fluid↗

Impact of early exercise radionuclide cineangiography on long-term prognosis after CABG.

BACKGROUND: The immediate benefits of coronary artery bypass grafting might be only transient. This prospective study examined the capability of exercise radionuclide cineangiography done shortly after coronary artery bypass grafting to predict outcome and long-term prognosis. METHODS: Results of exercise radionuclide cineangiography at 5.5 +/- 0.7 months (range, 4 to 8 months) postoperatively were correlated with mortality, major surgical and nonsurgical cardiac events, and cardiac event-free survival in 100 consecutive patients who underwent coronary artery bypass grafting. Stepwise logistic regression analysis was used to evaluate the incremental value of radionuclide cineangiography beyond the commonly used variables. RESULTS: Left ventricular ejection fraction at rest was normal (> or = 0.45) in 72 patients and increased on exercise in 58. The exercise radionuclide variables that correlated with future cardiac events were change and fractional change in heart rate, ST segment changes, anginal pain and congestive heart symptoms during exercise, rest ejection fraction, and change and fractional changes in ejection fraction. Predictors of event-free survival were exercise heart rate, rest ejection fraction, and change and fractional change in ejection fraction during exercise. Logistic regression analysis revealed that change in ejection fraction was an independent predictor of cardiac death and surgical interventions, whereas resting ejection fraction was a predictor of nonsurgical cardiac events. CONCLUSIONS: Postoperative exercise radionuclide cineangiography carried out soon after coronary artery bypass grafting had definite independent prognostic value and should be performed routinely to help decide treatment protocol.

Adult↗

Multiple antral ulcers in gastric sarcoid.

A 33-year-old woman suffered a week of severe epigastric pain and subsequent weight loss. On upper-gastrointestinal endoscopy several superficial ulcers were evident in the antral region. Mucosal biopsies from the ulcers showed epithelial cell granulomas. Even though no hilar lymphadenopathy was present on the chest radiograph and computed tomographic scan, the patient underwent bronchoscopy and transbronchial biopsy, which showed noncaseating epithelial cell granuloma, and bronchoalveolar lavage, which showed a lymphocytic pattern suggestive of sarcoidosis. Reports of gastric involvement in systemic sarcoidosis with no bilateral hilar lymphadenopathy are rare. We believe this is the first report of symptomatic gastric ulcers leading to endoscopic diagnosis of the underlying sarcoidosis.

Adult↗

Effect of IL-6 on alveolar fibroblast proliferation in interstitial lung diseases.

Alveolar macrophage-fibroblast interaction may be involved in the pathogenesis of interstitial lung diseases (ILD). Herein, we compared IL-6 secretion from alveolar macrophages (AM) and alveolar fibroblasts (AFb) recovered from patients with sarcoidosis (SA) and with diffuse interstitial fibrosis (DIF). Moreover, we evaluated the effect of IL-6 on the in vitro AFb proliferation in both diseases. AM and AFb from SA patients showed increased spontaneous secretion of IL-6 compared with cells from DIF subjects. Tumor necrosis factor-alpha (TNFalpha) and interleukin-1 (IL-1) enhanced IL-6 secretion and IL-6 mRNA transcription in AFb of SA patients. Addition of anti-IL-6 MoAbs increased AFb proliferation capacity in SA, but suppressed it in DIF. These results show that only SA AM and AFb secrete high levels of IL-6 which have suppressive effect on AFb proliferation. This may indicate a potential role of IL-6 in the fibrogenesis of ILD.

Cell Division↗

Effect of nedocromil sodium and cromoline sodium on atopic basophil function.

Nedocromil sodium (NS) is a new drug for the treatment of bronchial asthma. In the present study, we examined the effect of NS on basophil histamine release stimulated by anti-IgE, anti-IgE+IL-3 (interleukin-3) or ryegrass. The effect of cromoline Na (CrS) on histamine release from basophils to the same stimuli was compared. NS did not affect histamine release from basophils following anti-IgE alone or together with IL-3, but augmented the release following ryegrass. CrS did not affect histamine release after the same three stimuli. We concluded that NS and CrS do not affect bronchial asthma through direct inhibition of histamine release from basophils. Their action may be via an indirect effect on histamine-releasing factor.

Adolescent↗

Changes in sensitivity to methacholine after inhalation with distilled water: the role of the bronchoconstrictive response.

The inhalation of distilled water can induce bronchoconstriction and a transient increase in sensitivity to methacholine in asthmatics. The purpose of this study was to determine the role of the induced bronchoconstriction in the increased sensitivity to methacholine which follows the challenge with distilled water. Eighteen asthmatic children (age 9-17 yrs) were challenged by inhalation of distilled water. Bronchial responsiveness, the provocative concentration of methacholine producing a 20% decrease in forced expiratory volume in one second (PC20), was determined before inhalation of distilled water, and 1.5 and 24 h thereafter. Following inhalation of distilled water, eight patients (Group I) had a greater than 15% decrease in FEV1 (mean 23%); whereas, in the remaining 10 (Group II) the decrease was less than 7% (mean 1%). PC20 to methacholine, geometric mean and 95% confidence interval (CI), decreased transiently only at 1.5 h following inhalation of distilled water. The decrease was from 0.78 mg.ml-1 (95% CI 0.11-5.54 mg.ml-1) at baseline to 0.25 mg.ml-1 (95% CI 0.03-2.14 mg.ml-1) after challenge in Group I; and from 2.67 mg.ml-1 (95% CI 0.35-20.34 mg.ml-1) at baseline to 0.72 mg.ml-1 (95% CI 0.18-14.87 mg.ml-1) after challenge in Group II. The transient increase in sensitivity to methacholine observed following inhalation of distilled water occurred independently of the bronchoconstrictive response. This finding may have important clinical implications when hypo-osmolar solutions are used for delivery of drugs.

Adolescent↗

Long-term results of coronary artery bypass surgery in patients with severely depressed left ventricular function.

STUDY OBJECTIVE: The objective of the present study was to evaluate medium- and long-term results of coronary artery bypass grafting (CABG) in patients with severe left ventricular dysfunction (LVD). DESIGN: Prospective evaluation (clinical follow-up and equilibrium radionuclide angiography scan) of all the patients with severe LVD who underwent CABG from November 1986 to November 1991 at the Tel Aviv Medical Center and were referred to the Post Cardiac Surgery Follow-up Clinic at this institution. PATIENTS: Seventy-four consecutive patients (65 men, 9 women, aged 43 to 82 years; mean age, 68.2 years) with left ventricular ejection fraction (LVEF) of 30% or less who underwent isolated CABG (without automatic implantable cardioverter-defibrillator implantation, aneurysmectomy, valve replacement, or other open heart procedures) during a 5-year period and were discharged from hospitalization were prospectively evaluated. Preoperatively, 62% of patients had angina, 65% had congestive heart failure (CHF), and the LVEF ranged from 10 to 30%. The mean number of grafts was 2.98 per patient; the internal mammary artery (IMA) was used in 54 patients. The patients were followed up 4 to 96 months (mean, 64.9 months) post-surgery for survival, clinical status, and left ventricular function. RESULTS: Survival was 96%, 93.2%, 91.9%, 87.8%, 86.5%, 83.8%, and 83.8%, at 1, 2, 3, 4, 5, 6, and 7 years, respectively. Postoperatively, mean angina class improved from 2.9 to 1.4 (p < 0.0001) and mean CHF class improved from 2.7 to 1.8 (p < 0.0001). Mean LVEF improved from 23.5% preoperatively to 35.7% postoperatively (p < 0.0001). CONCLUSIONS: The following occur in patients with coronary artery disease and severe LVD undergoing CABG: (1) good medium- and long-term survival is attained; (2) angina class improves; (3) CHF class improves; (4) LVEF objectively improves; and (5). IMA can be used safely as a conduit.

Adult↗

Bayesian classification of vasculitis: a simulation study.

New classification criteria for vasculitic disorders have recently been proposed by the American College of Rheumatology. These classification criteria have limitations inherent to the method employed in their development. We propose a different approach to the quantitative analysis of the manifestations of vasculitis, which may improve the precision of classification criteria in this domain. Bayesian classifiers were developed for six vasculitides using literature-derived quantitative descriptions of these syndromes. These clinical data were also used in computer programs designed to generate simulations of vasculitis and control cases. The performance of Bayesian classifiers of vasculitis was then compared to that of the American College of Rheumatology criteria, using series of computer-simulated vasculitis cases. Bayesian classifiers identified simulated vasculitis cases with greater accuracy than those of the corresponding American College of Rheumatology 1990 vasculitis criteria in all six diseases studied. As predicted by theoretical considerations, Bayesian classifiers have the potential to identify vasculitis cases more accurately than the proposed American College of Rheumatology 1990 criteria.

Adolescent↗

The effect of exercise on basophil histamine release in patients with bronchial asthma.

There is increasing evidence for the role of basophils in allergic bronchial asthma. We studied the potential role of basophils in the pathogenesis of post-exercise-induced bronchoconstriction by measuring the histamine release from basophils both spontaneously and following ConA, FMLP, anti-IgE and TPA treatment. Two groups of patients with allergic asthma were studied: group I consisted of 8 patients with an exercise-induced fall in FEV1 of 20% or more, and group II had 7 patients with bronchial asthma who had less than a 5% fall in FEV1 following exercise. The mean spontaneous histamine release (SHR%) from basophils for group I was significantly larger than that of group II both before as well as at 5-10 and 60 min following exercise. The SHR% at baseline was 25 +/- 10 in group I (mean +/- SD) and 15 +/- 5 in group II (mean +/- SD). At 5-10 min following exercise it was 24 +/- 6 in group I and 11 +/- 2 in group II, while at 60 min following exercise it was 24 +/- 6 in group I and 17 +/- 2 in group II. There was no significant difference between the two groups in the effect of ConA, FMLP, anti-IgE or TPA treatment on basophil histamine release. The enhanced bronchoconstriction by exercise did not affect histamine release either spontaneously or following those 4 stimuli. It was concluded that, although patients with exercise-induced asthma have a greater degree of spontaneous histamine release, this is not affected by induced bronchoconstriction, a finding which does not support a role for basophils in exercise-induced asthma.

Adolescent↗

Evaluation of asymptomatic subjects with low forced expiratory ratios (FEV1/VC).

BACKGROUND: Heightened bronchial hyperreactivity is frequently associated with airflow limitation, atopy, or cigarette smoking. The purpose of this study was to evaluate healthy subjects with significantly low values of forced expiratory volume in one second/vital capacity % (FEV1/VC%) by measuring their airway response to exercise and methacholine challenge, compared with a control group with normal spirometric values. METHODS: Eighty four healthy subjects with significantly low flow rates (group A, FEV1/VC% < 2 SD% predicted) were evaluated and compared with 37 subjects with normal flow rates (group B). Static lung volumes, spirometric tests, exercise, and methacholine challenges were performed. RESULTS: Lung volumes were normal for both groups. Mean FEV1/VC% was 69% for group A and 82% for the control group. Salbutamol improved baseline FEV1 in eight subjects in group A (mean 15%), while methacholine induced a drop in FEV1 in 12 subjects. The dose-response curve to methacholine reached a plateau in all the responders. None of the subjects in the control group improved their baseline FEV1/VC% to salbutamol, but three showed bronchial hyperreactivity similar to those in group A. CONCLUSIONS: Bronchial hyperreactivity does not occur more often in asymptomatic subjects with mildly low FEV1/VC% so these subjects do not require special investigations for airway disease.

Adolescent↗

Eosinophilic lung reaction to aluminium and hard metal.

A nonsmoker drill polisher with interstitial lung disease is presented. The environmental exposure was mainly to aluminum oxide, aluminum silicate, and hard metals. Bronchoalveolar lavage revealed high eosinophilia, and transbronchial biopsy specimen disclosed interstitial pneumonia with giant cell infiltrates and peribronchiolar accumulation of macrophages laden with opaque dust. Mineralogic studies done from the tissue revealed a high concentration of exogenous particles that were identified as hard metals and aluminum silicate. These findings are compatible with hard metal pneumoconiosis.

Aluminum Compounds↗

Effect of budesonide on bronchial hyperresponsiveness and pulmonary function in patients with mild to moderate asthma.

Thirty-nine subjects were included in this double-blind, placebo-controlled study of bronchial hyperresponsiveness (BHR) in patients with mild to moderate asthma. The time-courses of change of FEV1, PEFR%, bronchial reactivity, and daily measures of asthma control were determined during 8 weeks of treatment after a run-in period of 2 weeks. Bronchial hyperresponsiveness was assessed by the methacholine provocation method, defined as the dose of methacholine causing a 20% fall of FEV1 compared with baseline values. The trends of FEV1 and the percentage change in PEFR from baseline were significantly different between groups, in favor of budesonide (P < .05). Patient assessments of the effect of treatment showed that PEF improved significantly in the budesonide group only. The budesonide group increased their tolerability for methacholine provocation by 1.8 DD (doubling dose), which tended to be higher compared with the 0.8 DD of the placebo group. It is evident from this study and previous studies that more data are needed to establish the dose-effect relationship with time and severity of the disease.

Adolescent↗

Mite asthma in childhood: a study of the relationship between exposure to house dust mites and disease activity.

BACKGROUND: Children with asthma are commonly sensitized to the house dust mite. METHODS: We took monthly measurements from July to December of the amount of mites in the mattresses of asthmatic children and correlated them with symptom score, pulmonary function, and airway hyperreactivity to methacholine. RESULTS: In spite of the high number of Dermatophagoides pteronyssinus throughout this period, symptom and treatment scores, as well as PC20 to methacholine, worsened during the months of September and October. CONCLUSIONS: It is concluded that when asthmatic children allergic to mites are exposed to high levels of mite allergen, the number of mites in the mattress dust no longer correlate with increased symptoms, and that other factors are more likely to be associated with exacerbation.

Adolescent↗

Suppressive mechanisms of alveolar macrophages in interstitial lung diseases: role of soluble factors and cell-to-cell contact.

Alveolar macrophages (AMs) from patients with interstitial lung diseases, such as sarcoidosis and idiopathic pulmonary fibrosis, suppress the phytohaemagglutinin (PHA) stimulation of autologous peripheral lymphocytes. The aim of this study was to determine whether the suppressive effect of alveolar macrophages of patients with interstitial lung disease is due, not only to the secretion of soluble factors prostaglandin E2 (PGE2), interleukin-1 (IL-1) but is also correlated to a direct effect of AMs on the expression of IL-2 receptors (IL-2R: CD25) and on the induction of IL-2 activity. We studied 26 subjects, 8 with sarcoidosis, 7 with idiopathic pulmonary fibrosis, and 11 controls. Alveolar macrophages of sarcoid and idiopathic pulmonary fibrosis patients suppressed proliferation of autologous peripheral lymphocytes by 68 +/- 14% and 53 +/- 4.5%, respectively, compared to enhancement of 19 +/- 11% in three controls and suppression of 25 +/- 11% in the other six controls; the difference between subjects with interstitial lung disease and controls was significant. As already reported, the alveolar macrophages of sarcoid patients secreted large amounts of IL-1 (184 +/- 59 U.ml-1) whereas the alveolar macrophages from idiopathic pulmonary fibrosis patients secreted large amounts of PGE2 (3.6 +/- 2 ng.ml-1 x 10(-5) cells) compared with 23 +/- 19 U.ml-1 IL-1 and 0.34 +/- 0.15 ng.ml-1 x 10(-5) cells respectively, of controls. Suppression by supernatants recovered from lipopolysaccharide (LPS) stimulated alveolar macrophages can only partially explain the high suppressive effect of alveolar macrophages of interstitial lung diseases.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗