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Biomedical subjects

G C Kane

Publications and source records attributed to G C Kane.

At least 19 recordsLinked to original sources
PubMed2005

Angiotensin II antagonism fails to ameliorate bleomycin-induced pulmonary fibrosis in mice.

Based on current evidence, transforming growth factor (TGF)-beta plays a central pathogenic role in the development of pulmonary fibrosis. There is growing evidence that angiotensin II can serve as a stimulus for TGF-beta-mediated lung fibrosis. However, the role of angiotensin II in the pathobiology of pulmonary fibrosis in vivo remains unclear and the therapeutic potential for targeting angiotensin II in a bleomycin-induced pulmonary fibrosis model is not well known. Therefore, the aim of this study was to test whether the angiotensin II antagonist, losartan, attenuated the development of bleomycin-induced pulmonary fibrosis in two distinct murine strains, C57/BL6 and Sv129. This was determined by histopathology and quantification of collagen content by hydroxyproline assay. Despite demonstrable angiotensin II antagonism in vivo and a reduction in measures of acute lung injury, losartan therapy, at a dose shown to reduce renal and cardiac fibrosis in mice, failed to significantly ameliorate bleomycin-induced pulmonary fibrosis. In conclusion, these data suggest that the pulmonary fibrotic disease process in vivo is not solely dependent on angiotensin II activity and the potential for angiotensin II receptor blockers as a therapeutic strategy in patients with pulmonary fibrosis may be limited.

Angiotensin II Type 1 Receptor Blockers↗
PubMed2001

Bronchial atresia with relapsing pulmonary infection in a middle-aged man.

Congenital bronchial atresia (CBA) is a rare disorder, first reported in 1953. Less than 100 cases are reported in the literature, mostly in young, asymptomatic male patients with involvement of the apical-posterior segment of the left upper lobe. Patients may complain of fever, cough, or shortness of breath, symptoms that result from post-obstructive, sometimes recurrent, infections. Chest radiography and computed tomography reveal a tubular branching density representing mucus impaction or mucocele with surrounding focal hyperinflation. Surgical excision is reserved for symptomatic cases. We report an unusual case of CBA in a middle-aged man with a history of relapsing infections, who was found to have an atretic superior segment of the left lower lobe, with surrounding areas of organizing pneumonia.

Activities of Daily Living↗
PubMed2000

Drug-grapefruit juice interactions.

Grapefruit juice, a beverage consumed in large quantities by the general population, is an inhibitor of the intestinal cytochrome P-450 3A4 system, which is responsible for the first-pass metabolism of many medications. Through the inhibition of this enzyme system, grapefruit juice interacts with a variety of medications, leading to elevation of their serum concentrations. Most notable are its effects on cyclosporine, some 1,4-dihydropyridine calcium antagonists, and some 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors. In the case of some drugs, these increased drug concentrations have been associated with an increased frequency of dose-dependent adverse effects. The P-glycoprotein pump, located in the brush border of the intestinal wall, also transports many cytochrome P-450 3A4 substrates, and this transporter also may be affected by grapefruit juice. This review discusses the proposed mechanisms of action and the medications involved in drug-grapefruit juice interactions and addresses the clinical implications of these interactions.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

A controlled trial of the effect of the 5-lipoxygenase inhibitor, zileuton, on lung inflammation produced by segmental antigen challenge in human beings.

BACKGROUND: Segmental antigen challenge (SAC) and bronchoalveolar lavage (BAL) have been proven useful for investigating IgE-mediated lung inflammation in volunteers with allergies. OBJECTIVE: This model was used to evaluate the pulmonary antiinflammatory effects of an experimental 5-lipoxygenase inhibitor (zileuton) in subjects allergic to ragweed. We hypothesized that decreased generation of leukotrienes by inhibition of the 5-lipoxygenase pathway of arachidonic acid metabolism would diminish the subsequent inflammatory response resulting from antigen challenge. METHODS: Ten subjects with allergies received zileuton or placebo, 600 mg administered orally four times a day for 8 days, and then underwent bronchoscopy, BAL of a control segment, and SAC in the contralateral lung followed by BAL of the challenged segment 24 hours later in a double-blind, placebo-controlled, crossover protocol. Urinary excretion of leukotriene E4 induced by antigen challenge plus total and differential cell counts and the amount of total protein, albumin, urea, and eosinophil cationic protein in BAL fluid were determined. RESULTS: A significant inhibition of leukotriene production (approximately 86%) was observed in subjects receiving zileuton. In addition, there was a statistically significant increase in eosinophils after antigen challenge (0.6 +/- 0.2 x 10(4) eosinophils/ml increasing to 49.0 +/- 25.0 x 10(4) in subjects receiving placebo, whereas the influx of eosinophils in subjects receiving zileuton was not statistically different from baseline (1.1 +/- 0.7 x 10(4) eosinophils/ml increasing to 16.5 +/- 4.1 x 10(4); analysis of variance for repeated measures with post hoc comparisons). CONCLUSIONS: Treatment with zileuton altered the inflammatory response after antigen challenge. Products of the 5-lipoxygenase pathway appear to be important in recruiting eosinophils to the lung after SAC.

Adult↗
PubMed1996

Lung involvement in systemic sclerosis (scleroderma): relation to classification based on extent of skin involvement or autoantibody status.

Lung involvement accounts for significant morbidity and is a leading cause of mortality in patients with systemic sclerosis (SSc). It has been shown that different patterns of pulmonary involvement are seen in different subtypes of SSc. This paper reports a retrospective review of 72 patients with SSc to determine whether disease classification according to the extent of skin involvement alone (diffuse vs. limited) or autoantibody status was predictive of pulmonary parenchymal involvement. The diagnosis of interstitial lung disease was based on pulmonary function tests and chest radiographs. Restrictive lung disease was common in both limited SSc (lSSc) and diffuse SSc (dSSc), occurring in 30% and 50% of these patients respectively (P = 0.16). Radiographic evidence of significant interstitial disease was also comparable between the groups [nine of 32 lSSc patients (28%) vs. six of 17 dSSc patients (32%), P = n.s.]. No significant difference in mean lung function was found between patients with anti-Scl 70 antibody (n = 12) compared to those without (n = 60) (TLC 79.0 +/- SE 5.1% predicted vs. 82.8 +/- 2.2, P = n.s.; DLCO 63.0 +/- 5.1 vs. 59.7 +/- 2.5, P = n.s.). By contrast, statistically significant differences in mean lung function were found between patients with anticentromere antibody (ACA) (n = 24) and those without ACA (n = 48) (TLC 98.6 +/- SE 3.9% predicted vs. 79.7 +/- 3.1%, P < 0.001); and less frequent radiographic evidence of severe interstitial disease (0 of 17 with significant interstitial changes on chest radiograph vs. 15 of 32 (47%), P = 0.002). It is concluded that classification of SSc patients on the basis of the distribution of skin involvement poorly predicts the occurrence of interstitial lung disease. On the other hand, ACA is highly associated with the absence of interstitial lung disease.

Adult↗
PubMed1995

Inhaled albuterol does not inhibit cellular influx or lung injury produced by segmental antigen challenge in humans.

Many experimental protocols and published guidelines for performing bronchoscopy, bronchoalveolar lavage (BAL), bronchial biopsies, and segmental antigen challenge (SAC) of allergic asthmatic subjects recommend treating subjects with a beta-agonist prior to the procedure. However, the effect of beta-agonist pretreatment has not been reported. In a retrospective analysis of ragweed allergic subjects undergoing bronchoscopy, SAC, and BAL, we examined the effect of albuterol pretreatment on cellular influx and lung injury produced by antigen challenge. Forty-eight subjects, 17 who received no pretreatment and 31 who received four puffs of albuterol prior to bronchoscopy, comprised the study groups. No parameter monitored in BAL fluid 24 h after SAC (total cells, macrophages, neutrophils, eosinophils, lymphocytes, total protein, albumin, or eosinophil cationic protein) differed in subjects pretreated with albuterol when compared with subjects who were not pretreated. Although additional, prospective studies are warranted, we conclude that beta-agonist pretreatment of experimental subjects does not alter many aspects of the inflammatory response produced by SAC.

Administration, Inhalation↗
PubMed1995

Insights into IgE-mediated lung inflammation derived from a study employing a 5-lipoxygenase inhibitor.

We have recently reported that the 5-lipoxygenase (5-LO) inhibitor, zileuton, alters lung inflammation produced by segmental antigen challenge in ragweed-allergic human subjects. Specifically, zileuton inhibited the urinary excretion of leukotriene E4 produced by antigen challenge, and the significant increase in bronchoalveolar lavage (BAL) eosinophils observed in subjects on placebo was not seen in subjects on zileuton. In this manuscript, we report additional data obtained during that study which provide information about mechanisms important during IgE-mediated inflammatory reactions in the lung. Three different areas are addressed: 1) the time to recovery of the lung from an IgE-mediated inflammatory response; 2) mechanisms related to the generation of cyclooxygenase products in the lung after antigen challenge and the effect of 5-LO inhibition on the production of cyclooxygenase metabolites; and 3) mechanisms responsible for the production of peptide leukotrienes in the lung and lung injury (as shown by albumin influx into the alveolar air space) 24 h after antigen challenge. We observed the following: 1) a significant BAL eosinophilia and basophilia remained 31 days (range 21-48) after segmental antigen challenge and bronchoalveolar lavage; 2) a decreased quantity of BAL cyclooxygenase products, as well as lipoxygenase products, in the presence of 5-LO inhibition; and 3) correlative analyses which suggest that while eosinophils appear most important for the production of peptide leukotrienes and lung injury 24 h after antigen challenge in subjects taking placebo, other effector mechanisms, perhaps those involving basophils and the initial mast cell triggering event, appear to gain in importance when the IgE-mediated inflammatory reaction is blunted by 5-LO inhibition.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1995

Pulmonary inflammation after segmental ragweed challenge in allergic asthmatic and nonasthmatic subjects.

Inflammatory reactions in the airways are thought to play an important role in asthma pathogenesis. The goal of this work was to test prospectively the hypothesis that the pulmonary inflammatory response to segmental antigen challenge is greater in allergic asthmatic (AA) subjects than in allergic nonasthmatic (ANA) subjects. A total of 46 ragweed-allergic subjects, 27 AA and 19 ANA, took part in these studies. Subjects had normal or nearly normal pulmonary function, were on no chronic medication, and were characterized as to their skin sensitivity to intradermal ragweed injection, their nonspecific responsiveness to methacholine, and the presence (or absence) of a late asthmatic response after whole-lung antigen challenge. Subjects then underwent bronchoscopy, bronchoalveolar lavage (BAL) of a control lung segment, antigen lung challenge of a contralateral lung segment with 5 ml of a concentration of ragweed solution 100-fold higher than that required to produce a positive skin reaction, and finally, BAL of the challenged segment after 24 h. AA did not differ from ANA in any inflammatory parameter measured in BAL fluid (total cells/ml, macrophages/ml, lymphocytes/ml, eosinophils/ml, neutrophils/ml, total protein, albumin, urea, or eosinophil cationic protein) 24 h after challenge. In addition, there was no relationship between nonspecific bronchial responsiveness to methacholine and eosinophils recruited to the lung by segmental antigen challenge. Rather, in both groups a marked inflammatory response was seen only in the subgroup of subjects who demonstrated a late airway reaction after whole-lung antigen challenge, regardless of disease classification.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

67Gallium scans in Löfgren's syndrome.

Comparison of 67Gallium scans of head and neck showed no significant difference in intensity of uptake between patients with Löfgren's syndrome and sarcoidosis patients with similar chest x rays having other modes of onset. Uptake was the same in the 12 white and 18 black patients studied. Thus, the increased bronchoaveolar lavage lymphocytosis which has been shown to be a feature of Löfgren's syndrome is not paralleled by gallium uptake. Gallium scores had no predictive value regarding outcome showing no significant difference between 13 patients who recovered within a year and 15 patients who developed chronic disease. The outcome was more favorable in white patients and in those whose onset was with Löfgren's syndrome.

Black People↗