Richard A. Matthay

Theophylline-induced seizures in adults. Correlation with serum concentrations.

Eight patients developed grand mal seizures during intravenous theophylline therapy. None had a history of neurologic disorder, and all were acutely ill with severe pulmonary or cardiovascular disease, or both. Serum theophylline concentrations obtained within 1 hour of the seizure ranged from 25 mug/ml to 70mug/ml, with a mean value (53 plus or minus 4.8 mug/ml) more than twice the upper limit of the recommended therapeutic concentration. This serum theophylline concentration was greater than the concentration found in a group of patients with less severe drug-related symptoms (35 plus or minus 1.8 mug/ml, P less than 0.01). A third group of patients without drug-related symptoms had a mean theophylline serum concentration of 19 plus or minus 2.0 mug/ml, which was less than that found in either group with toxicity symptoms (P less than 0.05). Factors predisposing to the high serum concentrations in the patients with seizures were both higher drug dosage, compared with the other groups (P less than 0.01), and hepatic dysfunction, which was more common in both groups with drug-related symptoms.

Lung Cancer: Epidemiology, Etiology, and Prevention

Lung cancer is the leading cause of cancer death in the United States and around the world. A vast majority of lung cancer deaths are attributable to cigarette smoking, and curbing the rates of cigarette smoking is imperative. Understanding the epidemiology and causal factors of lung cancer can provide additional foundation for disease prevention. This article focuses on modifiable risk factors, including tobacco smoking, occupational carcinogens, diet, and ionizing radiation. It also discusses briefly the molecular and genetic aspects of lung carcinogenesis.

Pulmonary manifestations of systemic lupus erythematosus: review of twelve cases of acute lupus pneumonitis.

Acute lupus pneumonitis was the presenting manifestation of systemic lupus erythematosus in six of 12 cases in this series. The clinical picture was characterized by severe dyspnea, tachypnea, fever and arterial hypoxemia. Radiographic findings included an acinar filling pattern which was invariably found in the lower lobes and was bilateral in 10 of the cases. Studies failed to reveal evidence of infection as a cause of the acute pulmonary infiltrates. All patients were treated with oxygen and corticosteroids; seven received azathioprine. Six patients survived and are clinically well 14 months to four years following their acute illness. Three of these patients have residual interstitial infiltrates with persistent pulmonary function test abnormalities indicating progression to chronic interstitial pneumonitis. Histologic sections of the lungs available from four patients revealed hyaline membranes and interstitial edema (four cases), acute alveolitis (two cases), arteriolar thrombosis (one case) and a prominent lymphocytic interstitial pneumonitis with organizing bronchiolitis (one case).

Assessment of cardiac performance with quantitative radionuclide angiocardiography: Right ventricular ejection fraction with reference to findings in chronic obstructive pulmonary disease

A reproducible noninvasive technique for measuring righ ventricular ejection fraction was developed using first pass quantitative radionuclide angiocardiography. Studies were obtained in the anterior position with a computerized multicrystal scintillation camera with high count rate capabilities. Right ventricular ejection fraction was calculated on a beat to beat basis from the high frequency components of the background-corrected right ventricular time-activity curve. In 50 normal adults, right ventricular ejection fraction averaged 55 percent (range of 45 to 65 percent). This radionuclide measure of right ventricular function was reproducible, with minimal inter- and intraobserver variability, and was sensitive to changes in inotropic state induced with isoproterenol. In 36 patients with chronic obstructive pulmonary disease, right ventricular ejection fraction ranged from 19 to 71 percent. All 10 patients with corpulmonale, as well as 9 additional patients, had an abnormal right ventricular ejection fraction. Arterial oxygen tension and forced expiratory volume were depressed significantly more in patients with abnormal right ventricular ejection fraction than in subjects with normal right ventricular function. There was no relation between abnormalities in right and left ventricular ejection fraction.

Physiologic correlates of right ventricular ejection fraction in chronic obstructive pulmonary disease: A combined radionuclide and hemodynamic study☆

Abstract The pathophysiologic correlates of right ventricular ejection fraction, as well as its relation to contractile function as assessed by systolic pressure-volume data, were evaluated in 20 patients with chronic obstructive pulmonary disease. Radionuclide and hemodynamic measurements were obtained simultaneously. Baseline determinations were obtained in all patients. In seven patients, studies were repeated after intravenous administration of sodium nitroprusside. This procedure allowed characterization of right ventricular performance at decreased afterload and provided two points necessary for definition of the right ventricular systolic pressure-volume relation. Seventeen of the 20 patients had a depressed right ventricular ejection fraction (less than 45 percent). There was a strong inverse linear correlation between right ventricular ejection fraction and afterload as assessed by peak or mean pulmonary arterial pressure (r = −0.81) and pulmonary vascular resistance index (r = −0.73). Right ventricular ejection fraction also correlated, although less strongly, with preload as assessed by right ventricular end-diastolic volume index (r = −0.56) and mean right atrial pressure (r = −0.51). It did not correlate with cardiac index, the ratio of peak pulmonary arterial pressure to right ventricular end-systolic volume index, arterial oxygen tension or left ventricular ejection fraction. After nitroprusside administration, mean arterial pressure, peak pulmonary arterial systolic pressure and pulmonary vascular resistance index decreased significantly. The slope (E) and the volume intercept (V 0 ) of each pressure-volume line were determined. Administration of dobutamine resulted in a leftward shift from the endsystolic pressure-volume line. There were poor correlations between E and right ventricular ejection fraction, as well as between E and the control ratio between pulmonary arterial systolic pressure and end-systolic volume index. These data demonstrate that, in addition to intrinsic contractile influences, right ventricular ejection fraction is highly dependent on afterload, but less dependent on preload. Right ventricular ejection fraction is a poor indicator of the slope of the systolic pressure-volume relation, raising questions concerning its use as an independent index of chamber contractility.

INTERSTITIAL LUNG DISEASE IN POLYMYOSITIS AND DERMATOMYOSITIS: ANALYSIS OF SIX CASES AND REVIEW OF THE LITERATURE

Interstitial pneumonitis may be the presenting manifestation of polymyositis-dermatomyositis, or may occur later in the evolution of the disease. The clinical picture is characterized by non-productive cough, dyspnea and hypoxemia. The chest radiograph demonstrates interstitial infiltrates with predilection for the lung bases, often with an alveolar pattern in addition. The histopathologic features are those of organizing and interstitial pneumonitis and pleuritis, with variable fibrosis. In the present series, the patients with mixed alveolar and interstitial infiltrates on chest radiograph and organizing pneumonia and bronchiolitis obliterans in addition to interstitial pneumonitis. In one patient evolution from pulmonary inflammation to interstitial fibrosis was demonstrated. The etiology of primary lung disease in PM-DM is not known, but cell-mediated autoimmunity to an unidentified component of lung tissue is suggested. Including the present series, 50 percent of patients have responded favorably to corticosteroids with decreased dyspnea, clearing of the chest radiograph and improved pulmonary function tests.

Pulmonary manifestations of systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is an autoimmune disease that primarily affects young women. The respiratory system is more commonly involved in SLE than in any other collagen vascular disease. SLE may affect virtually all components of the respiratory system, including the upper airway, lung parenchyma, pulmonary vasculature, pleura, and respiratory muscles. Respiratory system involvement ranges from symptomatic to fulminant and life threatening. This article reviews the pulmonary manifestations of SLE, including drug-induced SLE.

Right and Left Ventricular Exercise Performance in Chronic Obstructive Pulmonary Disease: Radionuclide Assessment

Right and left ventricular pump performance was assessed at rest and during upright bicycle exercise in 30 patients with chronic obstructive pulmonary disease and in 25 normal control subjects. Right ventricular and left ventricular ejection fractions were ascertained noninvasively using first-pass quantitative radionuclide angiocardiography. The normal ventricular response to exercise was at least a 5% absolute increase in the ejection fraction of either ventricle. In patients the predominant cardiac abnormality involved performance of the right ventricle. Right ventricular ejection fraction was abnormal at rest in eight patients. Twenty-three patients demonstrated an abnormal right ventricular response to submaximal exercise. Airway obstruction and arterial hypoxemia were significantly more severe in patients with abnormal right ventricular exercise reserve than in those with normal reserve. Abnormal left ventricular performance was infrequent either at rest (four patients) or during exercise (six patients). Thus, this radionuclide technique allows noninvasive assessment of biventricular exercise reserve in chronic obstructive pulmonary disease.

Effects of aminophylline upon right and left ventricular performance in chronic obstructive pulmonary disease: Noninvasive assessment by radionuclide angiocardiography

Abstract Although aminophylline is a widely used bronchodilator in chronic obstructive pulmonary disease (COPD), its effects upon cardiac performance have not been fully established. The effect of aminophylline upon right ventricular and left ventricular ejection fraction and the left ventricular ejection rate was evaluated by first-pass quantitative radionuclide angiocardiography in 15 patients with COPD, including four with cor pulmonale, and in five control subjects without cardiopulmonary disease. Aminophylline infusion (9 mg/kg) significantly increased the right ventricular ejection fraction (45 to 52 per cent), left ventricular ejection fraction (60 to 67 per cent) and left ventricular ejection rate (3.4 to 4.1 sec −1 ) in patients with COPD (all parameters, p −1 ) (p 1 ) and forced vital capacity (FVC) increased significantly in patients with COPD but not in control subjects. Arterial carbon dioxide tension decreased significantly in both groups (p These data indicate that aminophylline acutely enhances biventricular performance in COPD. Since comparable cardiovascular changes are induced in normal subjects in whom ventilatory function was not altered, the beneficial effects of aminophylline upon global ventricular performance appear to be independent of the degree of pulmonary compromise.

Cytotoxic drug-induced lung disease

Cytotoxic drugs, principally bleomycin, methotrexate and busulfan, have been associated with pulmonary toxicity. Cytotoxic drug-induced lung disease may be difficult to establish with certainty because other causes of pulmonary disease are frequently present. We discuss the clinical, roentgenographic and histologic effects of the administration of bleomycin, methotrexate, busulfan and other cytotoxic agents on the lungs and suggest that these agents may also cause pulmonary malignancies. We note the importance of careful patient monitoring and withdrawal of a demonstrated offending agent.