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Biomedical subjects

R H Winterbauer

Publications and source records attributed to R H Winterbauer.

13 recordsLinked to original sources

Azathioprine combined with prednisone in the treatment of idiopathic pulmonary fibrosis: a prospective double-blind, randomized, placebo-controlled clinical trial.

Twenty-seven newly diagnosed patients with idiopathic pulmonary fibrosis (IPF) who were previously untreated for IPF were enrolled in a prospective, double-blind, randomized, placebo-controlled study to compare the therapeutic effect of combined prednisone/azathioprine (n = 14) with prednisone plus placebo (n = 13). Prednisone was started at 1.5 mg/kg/day (not to exceed 100 mg/day) for the first 2 wk followed by a biweekly taper to a maintenance dose of 20 mg/day. Azathioprine was administered at a daily dose of 3 mg/kg (not to exceed 200 mg/day). The patients tolerated the use of azathioprine well with few associated side effects. Changes in lung function at 1 yr, as measured by resting alveolar-arterial oxygen difference P[A-a]O2, FVC, and single breath diffusing capacity for carbon monoxide (DLCOSB), were all somewhat better in the azathioprine/prednisone group compared with the prednisone alone group, although none of these comparisons were statistically significant. Six of 14 (43%) patients randomized to prednisone plus azathioprine died during the 9-yr follow-up period, compared with 10 of 13 (77%) patients randomized to prednisone plus placebo. A Cox model survival analysis shows a nonsignificant but potentially large survival advantage for azathioprine/prednisone (hazard ratio 0.48, with 95% confidence interval increasing from 0.17 to 1.38). When adjusted for age, the survival advantage of azathioprine/prednisone becomes marginally significant (hazard ratio 0.26, with 95% confidence interval increasing from 0.08 to 0.88; p = 0.02 by large sample approximation, p = 0.05 by randomization test). We conclude that combined prednisone and azathioprine is a safe and possibly effective regimen for the treatment of IPF.(ABSTRACT TRUNCATED AT 250 WORDS)

Azathioprine

Chronic dyspnea unexplained by history, physical examination, chest roentgenogram, and spirometry. Analysis of a seven-year experience.

The purpose of this article is to describe the spectrum and frequency of diseases presenting as unexplained dyspnea and to develop a logical diagnostic approach to such patients. Seventy-two consecutive physician-referred patients had dyspnea greater than one-month duration unexplained by the initial history, physical examination, chest roentgenogram, and spirometry. Patients underwent a standard diagnostic evaluation. A definite cause for dyspnea was recognized in 58 patients, and no answer was found in 14. Twenty-two diseases were recognized in the patient group. Dyspnea was due to pulmonary disease in 26 (36 percent) patients, cardiac disease in ten (14 percent) patients, hyperventilation in 14 (19 percent) patients, and only 3 patients had extrathoracic disease causing dyspnea. Age younger than 40 years, intermittent dyspnea, and normal alveolar-arterial oxygen pressure difference (P[A-a]O2) at rest breathing room air was strongly predictive of bronchial hyperreactivity or hyperventilation. No patient diagnosed as having disease of the lung parenchyma or vasculature had a P(A-a)O2 less than or equal to 20 mm Hg. The differential diagnosis to explain dyspnea in patients with nondirective histories, normal findings from physical examinations, normal chest roentgenograms, and normal spirograms is extensive. The patient's age and measurement of gas exchange at rest help to formulate a diagnostic approach.

Adult

Slowly resolving, chronic, and recurrent pneumonia.

Slowly resolving, chronic, and recurrent pneumonias are clinical patterns that are often misunderstood and mistreated. This article reviews the natural history, clinical presentation, roentgenography, bacteriology, and relation to underlying illnesses of each of these atypical forms of community-acquired pneumonia. Standard definitions are presented and provide the physician with a means to classify the pneumonias. Appropriate diagnostic evaluation and therapy are also discussed.

Anti-Bacterial Agents

Interstitial lung disease.

The interstitial lung diseases are comprised of a group of pulmonary disorders characterized clinically by diffuse infiltrates on the chest radiograph and histologically by distortion of the gas exchanging portion of the lung. The physiologic correlates are restriction of lung volumes and impaired oxygenation. The term "interstitial" when applied to these diseases is actually a misnomer because it implies that the inflammatory process is limited specifically to the area between the alveolar epithelial and capillary endothelial basement membranes. The diseases currently grouped as "interstitial" also frequently involve the alveolar epithelium, alveolar space, pulmonary microvasculature, and less commonly, the respiratory bronchioles, larger airways, and even the pleura. The enormous differential diagnosis of interstitial lung disease can be made manageable by understanding that pneumoconiosis, drug-induced disease, and hypersensitivity pneumonitis account for over 80% of the responsible entities and can usually be identified from the patient's history. The nine remaining diseases/disease categories include: sarcoidosis, idiopathic pulmonary fibrosis, bronchiolitis obliterans-organizing pneumonia, histiocytosis X, chronic eosinophilic pneumonia, collagen vascular disease-associated interstitial lung disease, granulomatous vasculitis (Wegener's granulomatosis, Churg-Strauss syndrome, lymphomatoid granulomatosis), Goodpasture's syndrome, and pulmonary alveolar proteinosis. The diagnosis of a specific interstitial lung disease can be made via various means including the patient's history, specific serologies, bronchoalveolar lavage, transbronchial biopsy, and biopsy of extrathoracic tissues or open lung biopsy. A directed diagnostic approach can be formulated based on an understanding of these techniques and a thorough knowledge of the clinical presentations and specific diagnostic criteria for each of the major diseases. This monograph will serve as a guide for the clinician to use in evaluating and treating patients with interstitial lung disease. We begin by reviewing the clinical presentation, diagnostic criteria, and management of specific interstitial lung diseases excluding pulmonary infection, neoplasm, and sarcoidosis. Pneumoconiosis and drug-induced syndromes are not discussed in detail, but the agents responsible and pertinent exposures are presented in tabular form in the discussion of the general diagnostic approach.

Biopsy

New diagnostic approaches to the hospitalized patient with pneumonia.

The accurate diagnosis of pneumonia remains a formidable challenge in clinical medicine. The use of sputum, blood, and pleural fluid cultures provides a diagnosis in less than 50% of patients. A number of invasive techniques have recently been applied to the diagnosis of pneumonia. The methods are uniformly designed to separate upper respiratory saprophytic bacterial populations from the organisms responsible for the lower respiratory infection. Preeminent among these techniques is the use of fiberoptic bronchoscopy coupled with quantitative bacterial culture and immunofluorescence demonstration of antibody-coated bacteria. The methodology and results of this technique are described in detail in this paper. Recent clinical experience using transtracheal aspiration, percutaneous needle aspiration of the lung, and open lung biopsy are also reviewed.

Bacteriological Techniques

Idiopathic fibrosing alveolitis: a review with emphasis on ultrastructural and immunohistochemical features.

Fibrosing alveolitis is a usually chronic pulmonary disease affecting middle-aged men and women and causing progressive dyspnea. This review discusses the nosologic, etiologic, immunopathogenic, histologic, immunohistochemical and ultrastructural features of this condition. A hypothesis is presented suggesting microvascular damage as the primary pathologic change in cases associated with collagen vascular diseases and viral pneumonia.

Acquired Immunodeficiency Syndrome

Diffuse interstitial pneumonitis. Clinicopathologic correlations in 20 patients treated with prednisone/azathioprine.

Twenty patients with diffuse interstitial pulmonary disease diagnosed by open lung biopsy received combined prednisone/azathioprine therapy. Twelve patients demonstrated improvement with therapy. Each patient's clinical presentation, roentgenologic features and pathologic findings were correlated with their therapeutic response. Patients with an illness of one year's duration or less had a more favorable response to therapy than patients with a greater than two year duration of illness. Patients with associated extrathoracic abnormalities (anemia, glomerulitis, hepatopathy) exhibited a better therapeutic response that those with only pulmonary disease. The biopsy material from each patient was quantitatively graded on 20 morphologic variables. Statistical analysis using multiple linear regression revealed that a single variable, degree of interstitial fibrosis, was more that 90 per cent accurate in separating those responsive to therapy from those who failed to respond. Patients who respond to treatment had less interstitial fibrosis. Neither the amount of alveolar septal inflammation nor intra-alveolar cellular reaction was discriminatory in predicting response to therapy. A beneficial response to therapy was reflected in both improved lung volumes and gas exchange. Eight patients appeared to have a selective beneficial effect from azathioprine.

Adult

Diffuse pulmonary injury associated with gold treatment.

Two patients had diffuse, reversible pulmonary injury possibly owing to gold sodium thiomalate treatment: a 32-year-old woman with chronic inflammatory arthritis compatible with seronegative rheumatoid arthritis and a 32-year-old man with shoulder arthralgia. The patients had received 420 mg and 325 mg of gold sodium thiomalate, respectively. Cough and dyspnea began in the seventh and fifth weeks of therapy, respectively. In both patients x-ray study showed bilateral pulmonary infiltrates, with no evidence of pleural disease. The woman had no other manifestations of hypersensitivity to gold. The man had exfoliative dermatitis fever and anemia. Lung biopsies from both patients revealed lymphocytes and plasma cells infiltrating the alveolar septa and interstitial fibrosis. The woman improved slowly during four months after discontinuation of therapy. Pulmonary symptoms recurred after additional gold therapy, and again resolved when gold was discontinued. The man, treated with prednisone, showed prompt remission and remains will without medication.

Acute Disease

The infectious complications of sarcoidosis: a current perspective.

The incidence of indections requiring hospitalization was determined in 122 patients with sarcoidosis. The group was remarkably free of infection except for three patients with Aspergillus mycetoma occurring in areas of long-standing parenchymal involvement with cystic degeneration. There was a single instance of complicating pulmonary tuberculosis, and the only extrathoracic infection was a single instance of disseminated herpes zoster. This study confirms that aspergillosis, not tuberculosis, is currently the most common infectious complication of sarcoidosis. Although previous case reports have suggested an increased incidence of invasive fungal infection in patients with sarcoidosis, there is little to support this concept. None of the patients in the present study group developed these fungal infections during a mean 7.2-year follow-up. The clinical presentation of many of the previously reported cases suggests that the entire course of the granulomatous illness was infectious in nature rather than sarcoidosis with complicating infection.

Adrenal Cortex Hormones