American physicians consider euthanasia.
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Biomedical subjects
Publications and source records attributed to S M Ayres.
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OBJECTIVE: To characterize mortality in persons diagnosed with primary pulmonary hypertension and to investigate factors associated with survival. DESIGN: Registry with prospective follow-up. SETTING: Thirty-two clinical centers in the United States participating in the Patient Registry for the Characterization of Primary Pulmonary Hypertension supported by the National Heart, Lung, and Blood Institute. PATIENTS: Patients (194) diagnosed at clinical centers between 1 July 1981 and 31 December 1985 and followed through 8 August 1988. MEASUREMENTS: At diagnosis, measurements of hemodynamic variables, pulmonary function, and gas exchange variables were taken in addition to information on demographic variables, medical history, and life-style. Patients were followed for survival at 6-month intervals. MAIN RESULTS: The estimated median survival of these patients was 2.8 years (95% Cl, 1.9 to 3.7 years). Estimated single-year survival rates were as follows: at 1 year, 68% (Cl, 61% to 75%); at 3 years, 48% (Cl, 41% to 55%); and at 5 years, 34% (Cl, 24% to 44%). Variables associated with poor survival included a New York Heart Association (NYHA) functional class of III or IV, presence of Raynaud phenomenon, elevated mean right atrial pressure, elevated mean pulmonary artery pressure, decreased cardiac index, and decreased diffusing capacity for carbon monoxide (DLCO). Drug therapy at entry or discharge was not associated with survival duration. CONCLUSIONS: Mortality was most closely associated with right ventricular hemodynamic function and can be characterized by means of an equation using three variables: mean pulmonary artery pressure, mean right atrial pressure, and cardiac index. Such an equation, once validated prospectively, could be used as an adjunct in planning treatment strategies and allocating medical resources.
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Qualitative and quantitative studies were performed on pulmonary blood vessels in lung tissue obtained by biopsy, pneumonectomy, or autopsy from 58 patients in the Registry of Primary Pulmonary Hypertension sponsored by the Heart, Lung, and Blood Institute of the National Institutes of Health. In 49 patients (84%), the hypertensive vascular disease involved predominantly or exclusively muscular pulmonary arteries and arterioles. In each of these 49 patients, pulmonary artery medial hypertrophy was observed, and in 48 patients, it was also associated with intimal or luminal lesions. On the basis of the predominant histopathologic features, 25 of the 48 patients were classified as having pulmonary arteriopathy with plexiform lesions characterized by a combination of concentric laminar intimal fibrosis, eccentric intimal fibrosis, and plexiform lesions; in nine of these 25, recanalized thrombi were also present. Pulmonary arteriopathy with thrombotic lesions, defined by the presence of both eccentric intimal fibrosis and recanalized thrombi but without plexiform lesions, was observed in 19 patients. Intimal fibrosis, either concentric or eccentric, without plexiform or thrombotic lesions was found in four patients. Among the remaining nine patients in the Registry, pulmonary veno-occlusive disease was present in seven and chronic pulmonary venous hypertension in one. Pulmonary blood vessels were microscopically normal in a lung biopsy specimen from another patient. In general, patients with plexiform lesions and those with veno-occlusive disease had a much poorer prognosis than patients with thrombotic lesions. The present study shows the existence of several distinct histopathologic patterns of pulmonary vascular disease in individuals with primary pulmonary hypertension diagnosed by standardized clinical and laboratory criteria.
The hemodynamic responses to acute vasodilator administration were evaluated in 163 patients who were entered into the National Institutes of Health Registry on Primary Pulmonary Hypertension (PPH) between 1981 and 1985. Of a total of 491 drug administrations in these patients, 135 administrations in 104 patients were performed in a manner acceptable to the Registry. A single vasodilator was tried in 79 patients and more than one vasodilator in 25 patients. Two-thirds of the patients were in New York Heart Association Functional Classes III or IV. When the effects of all vasodilators were grouped together, there were significant decreases from baseline in mean pulmonary artery pressure (60 +/- 2 to 57 +/- 2 mm Hg, p less than 0.05) and total pulmonary resistance index (32.5 +/- 1.7 to 25.1 +/- 1.4 mm Hg/L/min/m2, p less than 0.0001), and increases in cardiac index (2.1 +/- 0.1 to 2.7 +/- 0.1 L/min/m2, p less than 0.0001). Mean systemic blood pressure fell (88 +/- 1 to 79 +/- 1 mm Hg, p less than 0.0001), whereas PaO2 was unchanged (70 +/- 3 to 71 +/- 3 mm Hg, p = NS). A fall in total pulmonary resistance greater than 20% was observed in 55% of the adequate drug trials. Adverse effects occurred in 32 of the total 491 patient-drug trials and were generally minor. Hypotension requiring treatment developed in six patients. There were two deaths attributable to vasodilator administration. Patients who died or had hypotension requiring treatment had higher right atrial pressures than did other treated patients (15 +/- 2 versus 9 +/- 1 mm Hg, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
This study investigated the effects of emissions from the internal combustion engine on pulmonary function and respiratory symptoms in men collecting tolls and directing traffic in areas with high levels of air pollution. Bridge and tunnel officers (BTOs) were administered pulmonary function tests and respiratory questionnaires for up to 11 consecutive years (n = 944). Carboxyhemoglobin levels were also measured. Regression coefficients on year tested were calculated on 466 individuals (49% of all BTOs) tested at least 3 years. The tunnel workers had significantly lower FEV1S (forced expiratory volume at one second) and FVCs (forced vital capacity), respiratory symptoms, and higher carboxyhemoglobin levels than the bridge workers. BTOs working over 20 years had the lowest mean pulmonary function values, the steepest slopes, and the most respiratory symptoms. We believe that the data show an association between working as a bridge and tunnel officer and decreased pulmonary function and increased respiratory symptoms, but it was not readily evident whether the effects were of clinical importance.
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Eight patients in shock associated with acute myocardial infarctions were treated with dopamine. We titrated the dopamine dose to increase mean arterial pressure to 65-70 mm Hg and urine output to greater than 40 ml/hr. Increase of heart rate to 120-125 beats/min and occurrence of potentially dangerous arrhythmias were limiting end-points. Dopamine administration averaged 17.2 microgram/kg/min. Heart rate increased from 95 to 118 beats/min (P less than 0.001), and mean arterial pressure rose from 60 to 65 mm Hg (P less than 0.05). Dopamine increased myocardial contractility as indicated by increase in cardiac index and systolic ejection rate, with only moderate decrease in systemic vascular resistance. Pulmonary wedge pressure and right atrial pressure decreased from 23 to 18 mm Hg (P less than 0.05) and from 10 to 8 mm Hg (P less than 0.001) respectively. Improvement in hemodynamic status by dopamine was associated with deterioration of myocardial metabolism. Myocardial oxygen extraction ratios and arterial-coronary sinus oxygen differences increased from 73 to 76% (P less than 0.05) and from 13.02 to 14.19 ml/100 ml (P less than 0.02) respectively. Myocardial lactate production increased from -8 to -15% (P = 0.05). We conclude that dopamine improved cardiac performance at the expense of myocardial oxygenation and that dopamine is potentially harmful to acutely ischemic myocardium.
Improvement of myocardial oxygenation is a major goal in the treatment of ischaemic heart disease. Propranolol, 0-1 mg/kg intravenously, was administered to 20 patients with acute myocardial infarction without clinical evidence of left ventricular failure. The most important haemodynamic response was a substantial decrease in myocardial contractility. This was reflected by a fall in cardiac index (average of 0-4 l/min/M2, P less than 0-001) and of arterial mean pressure (average of 16 mmHg, P less than 0-001) with little change in systemic vascular resistance. Heart rate, not strikingly increased at the control state in the majority of patients, decreased an average of 7 beats/minute (P less than 0-001). Pulmonary wedge pressure varied; it decreased in 6 patients with high values (greater than 15 mmHg) prior to propranolol. These changes in wedge pressure in the presence of decreased contractility are probably related to improved left ventricular compliance, produced by propranolol. Propranolol markedly improved myocardial metabolism. Arterial-coronary sinus oxygen difference decreased an average of 0-72 ml/100 ml (P less than 0-001). Myocardial lactate production shifted to extraction (average of -8% to 14%) or the rate of lactate extraction increased (average of 20% to 29%). Coronary blood flow decreased an average of 13 ml/100 g/min (P less than 0-001). The finding, that myocardial metabolism improved, suggests that decrease in coronary blood flow was mediated by reduced myocardial oxygen requirements. None of the 20 patients developed left ventricular failure or other complications related to beta-adrenergic blockade. Severe chest pain, unresponsive to conventional therapy in four patients, was relieved by propranolol. These findings demonstrate that acutely administered propranolol improves myocardila oxygenation in patients with uncomplicated acute infarction without endangering perfusion of other vital organs.
The method is based on the selective activating capacity of dithiothreitol on creatine kinase isoenzyme MB, after isoenzyme MM is activated by glutathione. Isolated isoenzymes MM and MB of human and canine origin were assayed individually and in mixtures of known activities. When glutathione was present in the assay medium the activity of each isoenzyme could be measured individually, but glutathione did not activate isoenzyme MB if it was present in a mixture with MM. Dithiothreitol, added to the serum before assay, activated the isoenzyme MB in the mixture. Values for MB activities obtained for isolated isoenzyme MB and for the isoenzyme mixture after dithiothreitol was added averaged 110 and 111 U/liter, respectively (r = 0.998; y = 1.007 x + 0.298; n = 10). In the serum of 40 patients with documented acute transmural myocardial infarction, the mean proportion of isoenzyme MB activity measured in this way was 5.5% (coefficient of variation, 7.7%). Isoenzyme MB activities measured by use of dithiothreitol compared well with those obtained by conventional electrophoresis/spectrophotometry (r = 0.998; y = 1.09x -0.65) and spectrofluorometry (r = 0.996; y = 1.10 x + 0.80). The assay of MB activity by the dithiothreitol method was automated, by use of an Abbott Bichromatic Analyser and a Calbiochem Super-Stat Pack Kit. In 60 isoenzyme MB determinations the manual and automated method correlated well (r = 0.990; y = 1.0x -1.36). The simplicity of isoenzyme MB determination by use of dithiothreitol and its ease of automation allow routine monitoring of the isoenzyme activity in patients with ischemic heart disease.