Gene/Protein Disease Symptom Drug Enzyme Compound
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A series of four patients with pulmonary infiltrates, pleural effusions, hypoxemia, peripheral eosinophilia, and symptoms of dyspnea, fatigue, and weakness is reported. Lung tissue obtained in three patients revealed interstitial pneumonitis, small-to-medium-vessel mixed-cell vasculitis, and alveolar exudate of histiocytes and eosinophils. All patients reported ingestion of L-tryptophan-containing products at a time when an association between L-tryptophan and the eosinophilia-myalgia syndrome was established. This clinical pattern of pulmonary involvement may be part of the continuum of the eosinophilia-myalgia syndrome. The pathophysiology of this syndrome and the relationship with the ingestion of L-tryptophan-containing products have not yet been identified.
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PMID:Acute eosinophilic pulmonary disease associated with the ingestion of L-tryptophan-containing products. 198 92

We describe the cases of three women with pulmonary involvement in the eosinophilia-myalgia syndrome. The illness was characterized by elevated peripheral blood eosinophil counts, myalgias, fatigue, and dyspnea. Two of three patients had bilateral infiltrates on chest roentgenograms. All three had markedly decreased carbon monoxide diffusing capacities and pulmonary hypertension. High-dose prednisone therapy provided only partial resolution of the pulmonary symptoms. Open lung biopsy specimens showed chronic interstitial and perivascular infiltrates in two of the patients and moderate fibrointimal hyperplasia of pulmonary vasculature in the third. High-dose prednisone therapy prior to the biopsies may have modified the original histologic features.
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PMID:Pulmonary involvement in the eosinophilia-myalgia syndrome. 198 90

We describe a patient who developed fever, fatigue, muscle weakness, dyspnea, skin rash, and eosinophilia after taking "high doses" of tryptophan for insomnia for two years. A gallium-67 scan revealed diffuse increased uptake in the lung and no abnormal uptake in the muscular distribution. Bronchoscopy and biopsy confirmed inflammatory reactions with infiltration by eosinophils, mast cells, and lymphocytes. CT scan showed an interstitial alveolar pattern without fibrosis. EMG demonstrated diffuse myopathy. Muscle biopsy from the right thigh showed an inflammatory myositis with eosinophilic and lymphocytic infiltrations.
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PMID:Gallium uptake in tryptophan-related pulmonary disease. 199 38

1. Fifty patients with symptoms due to chronic heart failure despite diuretic therapy were randomised to receive additional treatment with either hydralazine or captopril. The dose was titrated; 24 received hydralazine and 26 captopril up to a maximum daily dosage of 225 mg and 75 mg respectively. Forty-three patients had coronary heart disease and seven dilated cardiomyopathy. 2. Dyspnoea and tiredness were assessed using a visual analogue scale (0-100) before and during 12 weeks' treatment. Captopril produced a significantly greater reduction in breathlessness (F = 31.6, P less than 0.001) and tiredness (F = 65.8, P less than 0.001) compared with hydralazine. 3. There was an increase in treadmill exercise time during treatment with both hydralazine (from 5.5 (3.47-7.53) min to 6.9 (4.87-8.93) min), and captopril (from 5.0 (3.05-6.95) min to 7.8 (5.85-9.75) min), but the degree of improvement was significantly greater in the patients treated with captopril (F = 7.4, P less than 0.001). 4. There was no significant change in right ventricular ejection fraction (from 27.9 (19.3-36.5)% to 28.7 (20.1-37.3)%) or left ventricular ejection fraction (from 22.2 (14.2-30.2)% to 23.9 (15.9-31.9)%) during treatment with hydralazine. However, both right and left ventricular ejection fraction increased significantly during treatment with captopril (from 27.1 (18.9-35.3)% to 32.0 (23.8-40.2)%, P less than 0.05; and from 25.0 (17.2-32.8)% to 29.6 (21.8-37.4)%, P less than 0.05 respectively). 5. These results suggest that in patients with symptoms due to chronic heart failure despite diuretic therapy, treatment with captopril produces a greater symptomatic and haemodynamic improvement than treatment with hydralazine.
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PMID:Which vasodilator drug in patients with chronic heart failure? A randomised comparison of captopril and hydralazine. 201 67

This prospective study of symptom-limited supine ergometry was conducted to determine the contributions of right ventricular (RV) and left ventricular (LV) systolic function to the exercise capacity of a cohort of patients with coronary artery disease (CAD). Patients with unstable angina, angiographically proven CAD (n = 53) and stable symptoms after medical therapy or angioplasty were included. Documented myocardial infarction (greater than or equal to 2 weeks before exercise) was present in 43 of 53 patients. Angina was the limiting symptom in 11 of 53; the other 42 stopped exercise with dyspnea or fatigue, or both. Oxygen consumption was measured on-line during exercise with a metabolic cart. RV ejection fraction and LV ejection fraction were measured by validated methods from gated blood pool radionuclide ventriculography. There were weak but statistically significant correlations between exercise oxygen consumption and exercise RV ejection fraction (r = 0.30, p less than 0.05) and between exercise oxygen consumption and exercise LV ejection fraction (r = 0.38, p less than 0.01). Multivariate regression analysis, including exercise RV ejection fraction, exercise LV ejection fraction and exercise heart rate versus exercise oxygen consumption revealed a better relation (r = 0.48, p less than 0.005) than any variable in univariate regression. The values of RV and LV ejection fraction at rest did not correlate significantly (r = 0.2, difference not significant), but the exercise values did correlate weakly (r = 0.41, p less than 0.01). The reserve of LV ejection fraction, defined as exercise minus rest value, correlated weakly with exercise oxygen consumption (r = 0.32, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Left and right ventricular systolic function and exercise capacity with coronary artery disease. 202 97

Impaired diastolic function of the hypertrophied and stiffened left ventricle is a characteristic feature of hypertrophic cardiomyopathy (Figure 1). Altered left ventricular filling dynamics and reduced left ventricular distensibility or increased left ventricular diastolic chamber stiffness are associated with reduced left ventricular stroke volume, increased left ventricular filling pressures and compressive effects on the coronary microcirculation. These factors contribute importantly to the clinical presentation of many patients, including symptoms of fatigue, dyspnea and angina pectoris. Reduced distensibility results both from factors determining the passive elastic properties of the ventricular chamber (including severity of hypertrophy, fibrosis and cellular disarray) and from factors influencing the rate and extent of active left ventricular relaxation (Figure 2). The factors contributing to impaired relaxation in hypertrophic cardiomyopathy are mediated via either inactivation dependent or load-dependent mechanisms. In laboratory animals, compromise of myocardial inactivation results in a persistent increase in intracellular calcium concentration and in prolonged interaction of the contractile proteins. Additionally, there is evidence for an increased number of active receptors for calcium antagonists and, lastly, for myocardial ischemia (Figure 3). Load-dependent mechanisms include diminished wall tension at the opening of the mitral valve, changes in afterload, contractility and coronary flow. Other factors are nonuniform and asynchronous regional ventricular function due to differing increases in thickness of the ventricular walls and ischemia (Figure 4). Calcium channel blockers exert a favorable influence on left ventricular relaxation and filling (Figure 5); verapamil and diltiazem are preferable to nifedipine. Verapamil increases left ventricular stroke volume without an increase in the end-diastolic pressure (Figure 6), reduces regional asynchrony if present, and leads to a more homogeneous regional diastolic filling (Figure 4).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Left ventricular diastolic function in hypertrophic cardiomyopathy. 202 81

The response of patients with chronic severe heart failure to extended infusions (greater than or equal to 48 hours) of milrinone was evaluated in a multicenter, baseline-controlled, phase III efficacy and safety trial in 189 patients in the United States. Milrinone was given as loading and maintenance infusions according to one of four dose regimens. An effective response was defined as greater than or equal to 20% increases in cardiac index or decreases in pulmonary wedge pressure. All loading doses (range, 37.5 to 75 micrograms/kg/10 min) were effective short term, and maximum response occurred at 15 minutes. For the three effective regimens, cardiac index increased initially (at 15 minutes) by 24% to 42%, and pulmonary wedge pressure decreased by 24% to 33%. Systemic vascular resistance was reduced by 15% to 31%. The maximal acute response was effective in 99% of individual patients. During maintenance therapy, effective responses were seen at infusion doses of 0.375, 0.50, and 0.75 micrograms/kg/min, whereas an infusion of 0.25 micrograms/kg/min was ineffective. During 2 days of maintenance therapy, cardiac index remained augmented by 34% to 39% for the low and intermediate doses and by 44% to 73% for the high-dose infusion regimen. Pulmonary wedge pressure decreased an average of 18% on day 1 and 30% on day 2. Systemic vascular resistance was reduced by 20% to 25%, and stroke work index was augmented by 21% to 58%. Symptomatic improvement was common during intravenous milrinone therapy for symptoms of dyspnea (61% response), orthopnea (63%), edema (62%), and fatigue (40%). Improvement occurred more frequently in those with worse baseline functional indexes and in those with greater hemodynamic responses to therapy. Safety and tolerance were exceptionally good for these patients with advanced heart failure.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hemodynamic and clinical benefits with intravenous milrinone in severe chronic heart failure: results of a multicenter study in the United States. 203 27

The pattern of oxygen (O2) consumption (VO2), carbon dioxide (CO2) production (VCO2), ventilatory and metabolic responses during and in recovery from supine bicycle exercise was examined in 18 patients with recent myocardial infarction. An increase in VO2 with increasing work load was accomplished by proportional increases in both cardiac output and the arteriovenous O2 difference. During recovery, however, the arteriovenous O2 difference rapidly decreased below levels at rest, whereas VO2 and cardiac output remained elevated, indicating that VO2 during recovery further depended on relatively high cardiac output. The ratio of VCO2 to VO2 further increased after exercise, suggesting that such cardiac output contributed to the remaining high CO2 flow to the lung and therefore enhanced ventilation. Increased arterial catecholamines during exercise remained elevated for the first 5 minutes of recovery. Arterial lactate during this period continued to increase and resulted in profound metabolic acidosis, causing alveolar hyperventilation after exercise. These results suggest that during recovery from exercise, cardiopulmonary responses remain enhanced because of continuing high cardiac output, resulting in subsequent high CO2 flow to the lung and metabolic acidosis, and that this may be associated with profound fatigue or dyspnea after exercise.
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PMID:Oxygen utilization, carbon dioxide elimination and ventilation during recovery from supine bicycle exercise 6 to 8 weeks after acute myocardial infarction. 203 36

To determine whether foot transcutaneous oxygen tension (TcPO2) and ankle systolic blood pressure (SBP) measure similar aspects of peripheral vascular occlusive disease (PVOD), the authors examined their relationship at rest and following treadmill exercise. Thirty-seven PVOD patients (mean age 69.2 +/- 0.8 years) rested supine for twenty minutes, followed by a progressive treadmill walking test at a constant speed of 2 mph. The initial grade was 0%; this increased 2% every two minutes until maximal claudication pain (n = 19) or until the occurrence of such limiting symptoms as volitional fatigue (n = 6), ST segment depression (n = 4), dyspnea (n = 3), multiple premature ventricular contractions (n = 2), and angina (n = 2). Patients then rested supine for fifteen minutes. Foot TcPO2 was recorded before, during, and after exercise, whereas ankle SBP was measured before and after exercise. At rest, a curvilinear relationship was found between foot TcPO2 and ankle SBP (foot TcPO2 = 41.89 + 0.22(ankle SBP) + 0.0005 (ankle SBP2); SEE = 9.2, R = 0.64, R2 = 0.41, p less than 0.001). In contrast, the relationship was stronger and more linear during recovery, particularly at the sixth minute (foot TcPO2) = 8.33 + 0.35 (ankle SBP); SEE = 13.6, R = 0.86, R2 = 0.73, p less than 0.001). At rest, foot TcPO2 and ankle SBP characterized different aspects of PVOD because they shared only 41% common variance. During recovery, they provided similar information because up to 73% of the variance was shared. It is concluded that foot TcPO2 should also be used to assess PVOD patients because unique information is obtained at rest and values can be recorded during exercise.
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PMID:Relationship between foot transcutaneous oxygen tension and ankle systolic blood pressure at rest and following exercise. 204 97

This is a review of the effects of E on the symptoms of CHF which affect patients' (pts) quality of life and the signs associated with pts' prognosis. The review is based on clinical studies which were included in the New Drug Application for Vasotec (enalapril maleate, MSD) in the United States. There were 3 open-label (242 pts) and 4 double-blind, placebo (P)-controlled (661 pts) studies of at least 1 month and up to about 2 years duration. One of these, the CONSENSUS Trial evaluated mortality in 253 pts with class IV CHF. Dyspnea and fatigue are considered the most disabling symptoms causing pts' functional impairment and thus reducing the quality of life. Left ventricular gallop, pulmonary rales, cardiomegaly, and ejection fractions are known to adversely effect pts' prognosis. Evaluations of these signs, symptoms, and scores related to these symptoms were included in most, but not all, studies. The pts' NYHA cardiac status was evaluated in all studies. E alleviated the signs and symptoms of CHF and improved various scores in significant number of pts. Pts' quality of life improved as indicated by the number of pts "feeling better" after Rx with E (p less than 0.01 vs P) in a multinational study of 256 pts; reductions of cardiomegaly and increases in ejection fraction were significantly greater in E than in P treated pts; and in severe CHF (CONSENSUS Trial) the mortality was significantly reduced (p less than 0.003 vs P).
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PMID:Enalapril in the treatment of congestive heart failure: effects on signs, symptoms and mortality. 204 70


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