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Biomedical subjects

P D Stein

Publications and source records attributed to P D Stein.

At least 19 recordsLinked to original sources

A prospective investigation of pulmonary embolism in women and men.

OBJECTIVE: The aim of this study was to compare, in women and men suspected of pulmonary embolism, the frequency, risk factors, diagnosis, and presentation of pulmonary embolism as well as the accuracy of the ventilation/perfusion scan (V/Q scan) as a diagnostic tool. DESIGN: Data were collected during a prospective study (the Prospective Investigation of Pulmonary Embolism Diagnosis) to establish the accuracy of the V/Q scan compared with pulmonary angiograms. SETTING: Six tertiary medical centers in Massachusetts, Michigan, Connecticut, Pennsylvania, and North Carolina. PARTICIPANTS: Patients suspected of pulmonary embolism for whom a request was made for a V/Q scan or pulmonary angiogram (496 women and 406 men). RESULTS: Women 50 years old and under had a decreased frequency of pulmonary embolism compared with men of that age (16% vs 32%), but there was no difference in patients over 50 years old (Breslow-Day test, P less than .01). Risk factors for pulmonary embolism, the usefulness of the V/Q scan, and 1-year mortality were not different for women and men. Estrogen use in women was not associated with an increased frequency of pulmonary embolism, except in women using oral contraceptives who had undergone surgery within 3 months; four of five (80%) had emboli compared with four of 28 (14%) age-matched surgical patients not using estrogens (P less than .01). CONCLUSION: Women 50 years old and under (even young women using oral contraceptives) who were suspected of having pulmonary emboli and were enrolled in the Prospective Investigation of Pulmonary Embolism Diagnosis study had a smaller frequency of pulmonary embolism than men of that age, The risk factors for pulmonary embolism were the same for women and men, except that women using oral contraceptives had an increased risk of pulmonary embolism following surgery. Although the V/Q scan was a useful tool in the preliminary evaluation for pulmonary embolism in these women, a pulmonary angiogram was often needed for accurate diagnosis.

Adolescent

Left ventricular response to submaximal exercise in endurance-trained athletes and sedentary adults.

This investigation examines the hypothesis that athletes increase stroke volume with submaximal exercise through an augmentation of left ventricular (LV) end-diastolic volume and a reduction of LV end-systolic volume, whereas sedentary adults only increase stroke volume modestly, because LV end-diastolic volume does not increase. Upright bicycle exercise was performed by 17 endurance-trained male athletes and 15 sedentary men. M-mode echocardiograms were obtained during submaximal exercise at predetermined heart rates. Athletes, at a heart rate of 130 beats/min, increased their stroke volume 67% from 72 +/- 18 ml to 120 +/- 26 ml (p less than 0.001). This resulted from an increase of LV end-diastolic volume from 119 +/- 23 to 152 +/- 28 ml (p less than 0.001) and a reduction in LV end-systolic volume from 46 +/- 14 to 31 +/- 9 ml (p less than 0.001). Sedentary men at the same heart rate increased stroke volume 22% from 63 +/- 15 to 77 +/- 21 ml (p less than 0.05). LV end-diastolic volume did not change (96 +/- 20 vs 97 +/- 28 ml) (p = not significant), but LV end-systolic volume decreased (33 +/- 11 vs 20 +/- 9 ml) (p less than 0.001). In conclusion, athletes increased cardiac output through a more prominent augmentation of stroke volume than sedentary subjects at submaximal exercise. This was accomplished through an augmentation of LV end-diastolic volume. This may have a conserving effect on myocardial oxygen consumption at these levels of exercise.

Adult

Relation of plain chest radiographic findings to pulmonary arterial pressure and arterial blood oxygen levels in patients with acute pulmonary embolism.

Abnormalities of the plain chest radiograph of 123 patients with acute pulmonary embolism (PE) and no prior cardiac or pulmonary disease were related to the pulmonary arterial mean pressure, the partial pressure of oxygen in arterial blood, and the alveolar-arterial oxygen gradient. Patients with either a prominent central pulmonary artery or cardiomegaly had higher pulmonary arterial mean pressures than did patients with atelectasis, a pulmonary parenchymal abnormality or pleural effusion (p less than 0.001). These radiographic findings give clues to the severity of pulmonary hypertension in acute PE and suggest that pulmonary infarction or hemorrhage is associated with less severe PE.

Acute Disease

Evaluation of left ventricular function during ejection.

Several ejection indices of left ventricular performance are described. The most sensitive is the rate of change of power, especially when measured at the time of peak left ventricular wall tension. When measured at peak tension, the rate of change of power reflects force-velocity-length relations and, therefore, is theoretically appealing. The rate of change of power itself incorporates terms shown to be of functional significance. Among these is the rate of change of flow. This expression is more readily measured than the rate of change of power and can be approximated noninvasively by the measurement of blood acceleration.

Animals

Left ventricular shape: a factor in the etiology of functional mitral regurgitation in heart failure.

The relationship between left ventricular (LV) shape and functional mitral regurgitation (MR) was examined in 18 dogs with long-standing heart failure produced by multiple sequential intracoronary microembolizations. Global LV shape changes were evaluated from angiographic silhouettes obtained at baseline (before embolization) and during heart failure. LV shape changes at end systole and end diastole were quantitated based upon the ratio of the major-to-minor axis and the sphericity index. Among the 18 dogs studied, 11 developed 1+ to 3+ MR during heart failure and seven did not. There was no difference among the two groups with respect to hemodynamics, LV ejection fraction, chamber volume, and regional wall motion. A significant difference, however, was observed between the two groups with respect to the global indexes of LV shape. In dogs with MR, the end-systolic major-to-minor axis ratio decreased 29 +/- 3% between baseline and heart failure compared with only a 16 +/- 3% decrease in dogs without MR (p less than 0.01). In dogs with MR, the end-systolic sphericity index increased 72 +/- 11% between baseline and heart failure compared with an increase of only 30 +/- 5% in dogs without MR (p less than 0.02). Significant and directionally similar differences were observed during end diastole. These data indicate that in heart failure functional MR is associated with a more spherical LV and is not the result of simple LV chamber enlargement. Shape changes of the LV that occur in heart failure may be an important determinant of functional MR.

Animals

Myocardial beta adrenoceptor and voltage sensitive calcium channel changes in a canine model of chronic heart failure.

Effects of chronic heart failure upon receptor binding and cardiac function were studied in mongrel dogs. Heart failure was induced by three to seven, graded, sequential, intracoronary microembolizations performed 1 to 3 weeks apart. Depressed systolic and diastolic left ventricular function, reduced cardiac output, increased systemic vascular resistance, increased plasma norepinephrine concentration, left ventricular hypertrophy, and dilation were associated with the development of heart failure in this model. Three months after the last embolization, the density and affinity of myocardial beta adrenoceptors and voltage sensitive calcium channels were quantified by analyzing saturation isotherms of specific radioligand binding. [3H]Dihydroalprenolol and [3H]nitrendipine bound specifically and with high affinity to cardiac beta adrenoceptors and calcium channels, respectively. Scatchard transformation of the specific binding of these radioligands in membranes prepared following intracoronary embolization demonstrated a 47% decrease in the density of [3H]dihydroalprenolol binding sites (605 +/- 20 fmol/mg, normal, vs. 323 +/- 18 fmol/mg, failed; P < 0.05) and a 20% decrease in [3H]nitredipine binding sites (371 +/- 11 fmol/mg, normal, vs. 298 +/- 17 fmol/mg, failed; P < 0.05). The binding equilibrium dissociation constants for [3H]dihydroalprenolol and [3H]nitrendipine were not significantly different between normal and failed myocardium. There was no difference in the sialic acid content in the sarcolemmal membranes prepared from normal and failed dog hearts (31.07 +/- 0.76 nmol/mg, normal, vs. 30.58 +/- 5.25 nmol/mg, failed). This is inconsistent with the selective purification of membranes utilized in these radioligand binding studies.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Mechanism of functional mitral regurgitation during acute myocardial ischemia.

The mechanism and temporal manifestation of functional mitral regurgitation after acute myocardial ischemia were examined in eight dogs. Regional ischemia was produced by selective microembolization of the left circumflex coronary artery. Mitral regurgitation and regional left ventricular wall motion abnormalities were evaluated with use of Doppler color flow mapping and two-dimensional echocardiography, respectively. Measurements were made at baseline (before embolization) and were repeated at 30 min and 3 weeks after embolization. Mitral regurgitation developed in all dogs 30 min after embolization and completely subsided 3 weeks later. There was no evidence of mitral valve prolapse, mitral anulus dilation or left ventricular segmental dyskinesia at any time during the study. Regional wall motion analysis showed only hypokinesia of the left ventricular segment overlying the papillary muscle at 30 min with subsequent normalization of the segment at 3 weeks. Mitral regurgitation was accompanied by an increase of the end-systolic distance between the mitral anulus plane and the point of coaptation of the mitral leaflets. This distance was 0.5 +/- 0.1 cm at baseline, increased to 0.9 +/- 0.1 cm 30 min after the embolization (p less than 0.001) and returned to near baseline (0.6 +/- 0.1 cm) 3 weeks after the embolization. These data indicate that mitral valve prolapse, mitral anulus dilation and regional left ventricular dyskinesia are not necessary conditions for the development of functional mitral regurgitation after acute myocardial ischemia. Instead, hypokinesia of the ventricular segment overlying the papillary muscle and leading to retraction of the mitral leaflets toward the apex appears to be a sufficient condition for incomplete leaflet coaptation.

Animals

Left ventricular shape changes during the course of evolving heart failure.

The temporal relationship between left ventricular (LV) shape changes and the development of LV dysfunction, dilation, and sympathoadrenergic hyperactivity was examined in 10 dogs with chronic heart failure produced by multiple sequential intracoronary microembolizations. LV shape was quantitated from serial ventriculograms based on the ratio of the major to minor axis at end systole and end diastole. Measurements were made at baseline (before embolizations) and were repeated at 2, 8, and 16 wk after the last embolization. A significant increase of LV sphericity was present at 2 wk, with only minimal changes occurring thereafter. Despite the tendency for LV shape changes to plateau between 2 and 16 wk, LV ejection fraction continued to decline (31 +/- 1 vs. 20 +/- 2%; P less than 0.001), and LV end-diastolic volume continued to increase (86 +/- 6 vs. 103 +/- 9 ml; P less than 0.01) as did plasma norepinephrine concentration (456 +/- 30 vs. 868 +/- 172 pg/ml; P less than 0.02). These data indicate that in the course of evolving heart failure, LV shape abnormalities precede the development of profound LV dysfunction, dilation, and overt activation of the sympathetic nervous system.

Adrenal Glands

Complications and validity of pulmonary angiography in acute pulmonary embolism.

BACKGROUND: The Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED) addressed the value of ventilation/perfusion scans in acute pulmonary embolism (PE). The present study evaluates the risks and diagnostic validity of pulmonary angiography in 1,111 patients who underwent angiography in PIOPED: METHODS AND RESULTS: Complications were death in five (0.5%), major nonfatal complications in nine (1%), and less significant or minor in 60 (5%). More fatal or major nonfatal complications occurred in patients from the medical intensive care unit than elsewhere: five of 122 (4%) versus nine of 989 (1%) (p less than 0.02). Pulmonary artery pressure, volume of contrast material, and presence of PE did not significantly affect the frequency of complications. Renal dysfunction, either major (requiring dialysis) or less severe, occurred in 13 of 1,111 (1%). Patients who developed renal dysfunction after angiography were older than those who did not have renal dysfunction: 74 +/- 13 years versus 57 +/- 17 years (p less than 0.001). Angiograms were nondiagnostic in 35 of 1,111 (3%), and studies were incomplete in 12 of 1,111 (1%), usually because of a complication. Surveillance after negative angiograms showed PE in four of 675 (0.6%). Angiograms, interpreted on the basis of consensus readings, resulted in an unchallenged diagnosis in 96%. CONCLUSIONS: The risks of pulmonary angiography were sufficiently low to justify it as a diagnostic tool in the appropriate clinical setting. Clinical judgment is probably the most important consideration in the assessment of risk.

Acute Disease

Left atrial contribution to ventricular filling during the course of evolving heart failure.

BACKGROUND: Abnormal left ventricular (LV) filling has been observed in patients with heart failure and is characterized by marked heterogeneity of mitral inflow velocity. In the present study, the contribution of the left atrium to LV filling was examined in eight dogs during the course of evolving heart failure. METHODS AND RESULTS: Heart failure was produced by multiple sequential intracoronary embolizations with microspheres. Pulsed Doppler echocardiography was used to measure mitral inflow velocity at baseline, before embolization, and at 3, 8, 15, 23, and 33 weeks after initiation of microembolization. The early rapid LV filling (Ei) and late left atrial filling (Ai) components were quantitated based on the time-velocity integral of the early and late mitral inflow velocity waveforms, respectively. Ei decreased progressively from 7.6 +/- 1.5 cm at baseline to 4.0 +/- 0.4 cm at 33 weeks (p less than 0.01). In contrast, Ai initially increased from 1.8 +/- 0.9 cm at baseline to 2.7 +/- 0.4 cm at 3 weeks (p less than 0.01) and subsequently decreased gradually to below baseline values reaching 0.8 +/- 0.4 cm at 33 weeks (p less than 0.01). These temporal changes of Ei and Ai were accompanied by a gradual reduction of LV ejection fraction (56 +/- 5% versus 22 +/- 2%) (p less than 0.01) (baseline versus 33 weeks) and by a gradual increase of LV end-diastolic wall stress (24 +/- 7 versus 92 +/- 8 g/cm2) (p less than 0.01), left atrial dimension (2.4 +/- 0.2 cm to 3.3 +/- 0.3 cm) (p less than 0.01), and left atrial fractional shortening (22 +/- 3% versus 15 +/- 2%) (p less than 0.01). CONCLUSIONS: The initial rise in left atrium contribution to LV filling may represent a compensatory response to the diminution of the rapid early component of LV filling. With further progression of LV dysfunction, the left atrium contribution to LV filling gradually decreased. This reduction may be mediated by increased workload imposed on the left atrial myocardium due to increased LV diastolic wall stress, which, over time, may have lead to intrinsic left atrium dysfunction.

Animals

The diagnosis of acute pulmonary embolism in patients with chronic obstructive pulmonary disease.

The clinical features and noninvasive tests, including ventilation perfusion (V/Q) lung scans, were assessed in 108 patients with chronic obstructive pulmonary disease (COPD) suspected of having pulmonary embolism (PE). Twenty-one (19 percent) of 108 patients had PE. In the majority of patients, it was impossible to distinguish between patients with and without PE by clinical assessment alone. However, when a high clinical index of suspicion was present, PE was confirmed by angiography in three of three patients, but the V/Q scan was of intermediate probability. No roentgenographic abnormalities distinguished between PE and no PE. There was no difference between the alveolar-arterial oxygen gradients in either group, nor was there evidence of a reduction in the PaCO2 in patients with PE who had prior hypercapnia. Among the 108 patients with COPD, high, intermediate, low, and normal/near normal probability scans were present in 5 percent, 60 percent, 30 percent, and 5 percent, respectively. The frequency of PE in these V/Q scan categories was five (100 percent) of five, 14 (22 percent) of 65, two (6 percent) of 33, and zero (0 percent) of five, respectively. In conclusion, in the majority of patients, the V/Q scan diagnosis is usually intermediate and such patients require further investigational studies, including angiography. However, among the few patients who demonstrated a high probability lung scan, there was a high positive predictive value for PE effectively avoiding the need for further studies. In those patients with low probability or near normal/normal V/Q scans, the negative predictive value was not lower than the general hospital population.

Acute Disease

Diagnosis of acute pulmonary embolism in the elderly.

The diagnostic features of acute pulmonary embolism among 72 patients greater than or equal to 70 years old were evaluated and compared with characteristics of pulmonary embolism among 144 patients 40 to 69 years and 44 patients less than 40 years old. Syndromes characterized by either 1) pleuritic pain or hemoptysis, 2) isolated dyspnea, or 3) circulatory collapse were observed with comparable frequency among patients greater than or equal to 70 years old and younger patients. One of these presenting syndromes occurred in 64 (89%) of the 72 patients greater than or equal to 70 years old. Those who did not show these syndromes were identified on the basis of unexpected radiographic abnormalities, which may have been accompanied by tachypnea or a history of thrombophlebitis. Among the 72 patients greater than or equal to 70 years with pulmonary embolism, dyspnea or tachypnea (respirations greater than or equal to 20/min) occurred in 66 (92%), dyspnea or tachypnea or pleuritic pain in 68 (94%) and dyspnea or tachypnea or radiographic evidence of atelectasis or a parenchymal abnormality in 72 (100%). Complications of angiography were evaluated among patients with and without pulmonary embolism. Major complications of pulmonary angiography among patients greater than or equal to 70 years old (2 [1%] of 200) were not more frequent than among younger patients (6 [1.1%] of 562) (p = NS). However, renal failure (major or minor) was more frequent in patients greater than or equal to 70 years old than in younger patients (6 [3%] of 200 versus 4 [0.7%] of 562) (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease

Left ventricular shape as a determinant of functional mitral regurgitation in patients with severe heart failure secondary to either coronary artery disease or idiopathic dilated cardiomyopathy.

The relation between left ventricular (LV) shape and functional mitral regurgitation (MR) was evaluated in 39 patients with congestive heart failure. Heart failure was due to coronary artery disease in 23 patients (group I) and to idiopathic dilated cardiomyopathy in 16 (group II). LV shape was quantitated based on the ratio of LV major-to-minor axis and LV sphericity index calculated at end-systole and end-diastole. In group I, 9 patients had angiographic evidence of MR and 14 did not. In group II, 10 patients had MR and 6 did not. Within each group, there were no differences between patients with and without MR with regard to LV chamber volume and regional segmental wall motion abnormalities. In both groups, however, a significant difference was observed between patients with and without MR with respect to end-systolic and end-diastolic LV shape indexes. In group I, the end-systolic major-to-minor axis ratio was lower in patients with (1.42 +/- 0.04) than without (1.72 +/- 0.05) MR (p less than 0.001). Similar differences were observed in group II (1.41 +/- 0.06 vs 1.69 +/- 0.04) (p less than 0.01). In group I, the end-systolic sphericity index was also greater in patients with (0.32 +/- 0.02) than without (0.25 +/- 0.01) MR (p less than 0.02). Similar differences were observed in group II (0.37 +/- 0.03 vs 0.26 +/- 0.01) (p less than 0.02). These data indicate that in patients with severe heart failure, functional MR is present in those who manifest a more spherical LV cavity.

Cardiomyopathy, Dilated

Usefulness of noninvasive diagnostic tools for diagnosis of acute pulmonary embolism in patients with a normal chest radiograph.

The value of bedside examination and noninvasive tests in the diagnosis of acute pulmonary embolism (PE) among patients with a normal chest radiograph was investigated. Normal chest radiographs were present in 20 of 260 patients (8%) with acute PE and in 113 of 642 (18%) with suspected acute PE, in whom the diagnosis was excluded. A partial pressure of oxygen in arterial blood less than or equal to 70 mm Hg in a dyspneic patient with a normal chest radiograph was more often seen among patients with PE (9 of 17, 53%) than among patients in whom PE was excluded (18 of 93, 19%; p less than 0.01). However, no combinations of blood gases, signs and symptoms were strictly diagnostic. High probability ventilation/perfusion scans among patients with a normal chest radiograph were indicative of PE in only 6 of 9 patients (67%). Among patients with low-probability ventilation/perfusion scans, 8 of 47 (17%) had PE. This study showed that the combination of dyspnea and hypoxia in a patient with a normal chest radiograph is a useful clue to the diagnosis of PE. Although intuition suggested that ventilation/perfusion scans would yield better results in patients with a normal chest radiograph, the ability to diagnose PE by ventilation/perfusion scans in this subset of patients was not enhanced, except by a reduction of the percentage of patients with intermediate probability scans.

Acute Disease