Value of noninvasive techniques for predicting early complications in patients with clinical class II acute myocardial infarction

Twenty-six consecutive patients with acute clinical class II myocardial infarction were prospectively evaluated to assess the ability of two-dimensional echocardiography and gated equilibrium radionuclide angiography to predict early morbidity and mortality. Within 48 hours of the onset of symptoms, right heart catheterization, two-dimensional echocardiography and radionuclide angiography were performed. Serious in-hospital complications developed in 7 patients (27%, Group I), while the remaining 19 patients (Group II) had no complications. Mean left ventricular stroke work index was the only hemodynamic variable that differed significantly between Group I and Group II (28 +/- 8 [standard deviation] vs. 39 +/- 13 g-m/m2, respectively, p less than 0.02). Also, Group I compared with Group II had a significantly lower mean left ventricular ejection fraction by two-dimensional echocardiography (26 +/- 5 vs. 51 +/- 10%, p less than 0.001) or by radionuclide angiography (29 +/- 9 vs. 46 +/- 12%, p less than 0.001). Similarly, Group I had a higher average wall motion index than Group II by both techniques (2.2 +/- 0.2 vs. 1.7 +/- 0.3, p less than 0.001 by two-dimensional echocardiography, and 2.1 +/- 0.3 vs. 1.7 +/- 0.3, p less than 0.001 by radionuclide angiography). Selected stepwise multiple regression analysis demonstrated that left ventricular ejection fraction or wall motion index, by two-dimensional echocardiography or radionuclide angiography, had additional value to a history of prior myocardial infarction for predicting in-hospital complications in patients with class II infarction.(ABSTRACT TRUNCATED AT 250 WORDS)     

Serial measurements of left ventricular ejection fraction by radionuclide angiography early and late after myocardial infarction

The left ventricular ejection fraction was determined serially with radioisotope angiography in 63 patients with acute myocardial infarction. After the peripheral injection of a bolus of technetium-99m, precordial radioactivity was recorded with a gamma scintillation camera and the ejection fraction calculated from the high frequency left ventricular time-activity curve. Since this technique requires no assumptions with respect to left ventricular geometry, it is particularly useful in patients with segmental left ventricular dysfunction. Serial measurements during the first 5 days after hospital admission were made in 50 patients, 30 of whom were studied during the subsequent 2 to 39 months (mean 19.9 months). Late follow-up serial studies were also performed in an additional 13 patients who had only one measurement of the left ventricular ejection fraction during the early postinfarction period.Early after infarction, the left ventricular ejection fraction was normal (more than 0.52) in only 15 of the 63 patients, and averaged 0.52 ± 0.05 (standard deviation) in the 27 patients with an uncomplicated infarct. The ejection fraction was reduced in 24 patients with mild to moderate left ventricular failure (0.40 ± 0.05, P < 0.0001) and in the 12 patients with overt pulmonary edema (0.33 ± 0.07, P < 0.0001). In 35 patients the ejection fraction correlated with the mean pulmonary arterial wedge pressure (r = 0.72). In 15 patients with normal left ventricular wall motion by heart motion videotracking, the ejection fraction was significantly higher (0.53 ± 0.08) than in the 26 patients with regional left ventricular dysfunction (0.41 ± 0.10, P < 0.0001). During the early postinfarction period, the left ventricular ejection fraction improved in 55 percent of patients and remained unchanged or decreased in 45 percent. A further increase in the ejection fraction was noted in 61 percent of patients during the late follow-up period. Patients with an initially low or decreasing ejection fraction had a significantly greater incidence of early mortality and left ventricular dysfunction (P < 0.02) than those whose ejection fraction was normal or improved to normal early after infarction. These data indicate that the ejection fraction is a sensitive indicator of left ventricular function after acute myocardial infarction and that serial measurements are helpful in predicting early mortality and morbidity.     

Comparative value of 2-dimensional echocardiography and radionuclide angiography for quantitating changes in left ventricular performance during exercise limited by angina pectoris

To compare left ventricular (LV) ejection fraction (EF) measurements made during exercise by 2-dimensional echocardiography (2-D echo) and gated equilibrium radionuclide angiography (RNA), 18 patients with angina pectoris were studied during graded upright bicycle ergometry. For RNA, the left anterior oblique view was used with the patient grasping the camera gantry during the 2-minute count acquisition required for EF calculation. For 2-D echo, biapical views were recorded with the patient's arms resting on a platform, and EF was calculated from volume measurements made using Simpson's rule. Exercise duration was similar for both studies, but EF at maximal exertion was higher by RNA than by 2-D echo (46 ± 15 % vs 35 ± 15 %, p < 0.001). However, echo EF determined 1 minute before maximal exertion, which corresponded to the midpoint of the 2-minute count collection period for RNA, was similar to the RNA value at maximal exercise (44 ± 12 %). Analysis of individual EF values by 2-D echo at rest, at 1 minute before maximal exercise and at maximum exercise showed that there was little change in EF during submaximal exercise, but that EF decreased considerably at maximal exertion when the patients had angina pectoris. Therefore, when the time frame of data acquisition is considered, exercise 2-D echo and gated equilibrium RNA provide similar information regarding LVEF. The latter has the advantage of a 100 % successful study frequency and the former is superior in its ability to detect the rapid changes in LV performance during exercise-limiting symptoms.     

Mechanism of inferior electrocardiographic ST-segment depression during acute anterior myocardial infarction in a baboon model

Controversy exists concerning the mechanism of electrocardiographic (ECG) ST-segment depression in leads remote from an area of acute myocardial infarction. Thus, 13 baboons were studied during ligation of the distal third of the left anterior descending coronary artery. The morphologic pattern of the ECG limb leads in the supine baboons resembled that of an asthenic human and did not change when the chest was opened. The visually apparent infarct area of the distal anterior wall was confirmed by epicardial ECG mapping 30 minutes after ligation, and by tissue creatine kinase and histologic study at 24 hours. All 13 baboons had ST depression in leads III and aVF of 0.1 to 1.2 mV at 30 minutes, and 11 of 13 had similar changes in lead II. Also, all 13 baboons had ST elevation in lead aVL (n = 10) or aVR (n = 11), suggesting that the ST vector from the infarct area was directed away from the inferior leads. In no baboon did inferoposterior wall ventricular epicardial mapping show evidence of myocardial ischemia, and mean creatine kinase content from the infarct sites was markedly lower than that from posteroinferior sites (12.7 +/- 2.8 vs 20.6 +/- 2.1 IU/mg protein, p less than 0.01). In addition, the inferoposterior myocardium was normal histologically. In conclusion, acute myocardial infarction often results in reciprocal ST depression at sites distant from the area of acute necrosis and need not represent "ischemia at a distance."     

Accurate estimates of absolute left ventricular volumes from equilibrium radionuclide angiographic count data using a simple geometric attenuation correction

To simplify and clarify the methods of obtaining attenuation-corrected equilibrium radionuclide angiographic estimates of absolute left ventricular volumes, 27 patients who also had biplane contrast cineangiography were evaluated. Background-corrected left ventricular end-diastolic and end-systolic counts were obtained by semiautomated variable and hand-drawn regions of interest and were normalized to cardiac cycles processed, frame rate and blood sample counts. Blood sample counts were acquired on (d degree) and at a distance (d') from the collimator. A simple geometric attenuation correction was performed to obtain absolute left ventricular volume estimates. Using blood sample counts obtained at d degree or d', the attentuation-corrected radionuclide left ventricular end-diastolic volume estimates using both region of interest selection methods correlated with the cineangiographic end-diastolic volumes (r = 0.95 to 0.96). However, both mean radionuclide semiautomated variable left ventricular end-diastolic volumes (179 +/- 100 [+/- 1 standard deviation] and 185 +/- 102 ml, p less than 0.001) were smaller than the average cineangiographic end-diastolic volume (217 +/- 102 ml), and both mean hand-drawn left ventricular end-diastolic volumes (212 +/- 104 and 220 +/- 106 ml) did not differ from the average cineangiographic end-diastolic volume. Using the blood sample counts obtained at d degree or d', the attenuation-corrected radionuclide left ventricular end-systolic volume estimates using both region of interest selection methods correlated with the cineangiographic end-systolic volumes (r = 0.96 to 0.98). Also, using blood sample counts at d degree, the mean radionuclide semiautomated variable left ventricular end-systolic volume (116 +/- 98 ml, p less than 0.05) was less than the average cineangiographic end-systolic volume (128 +/- 98 ml), and the other radionuclide end-systolic volumes did not differ from the average cineangiographic end-systolic volume. Therefore, it is concluded that: 1) a simple geometric attenuation-correction of radionuclide left ventricular end-diastolic and end-systolic count data provides accurate estimates of biplane cineangiographic end-diastolic and end-systolic volumes; and 2) the hand-drawn region of interest selection method, unlike the semiautomated variable method that underestimates end-diastolic and end-systolic volumes, provides more accurate estimates of biplane cineangiographic left ventricular volumes irrespective of the distance blood sample counts are acquired from the collimator.     

Value of the tricuspid valve echogram for estimating right ventricular end-diastolic pressure during vasodilator therapy

To evaluate the potential usefulness of the tricuspid valve echogram for assessing right ventricular end-diastolic pressure, 9 patients with right heart failure and 10 normal subjects were studied. In the nine patients, the initial P-R interval of 184 ± 26 (±1 standard deviation) ms did not differ significantly from the normal subjects' value of 170 ± 17 ms; however, the A-C Interval of 162 ± 23 ms was significantly longer (p < 0.001) and the PR-AC interval of 21 ± 16 ms was shorter (p < 0.001) when compared with corresponding control measurements. Nitroprusside infusion significantly decreased the right ventricular end-diastolic pressure from 15 ± 4 to 8 ± 4 mm Hg in the nine patients (p < 0.001). Additionally, it decreased the average A-C interval to 137 ± 25 ms (p < 0.001) and the mean PR-AC interval to 46 ± 18 ms (p < 0.05). However, the PR-AC interval did not correlate closely with the right ventricular end-diastolic pressure. Furthermore, it did not separate elevated right ventricular end-diastolic pressures from normal pressures. However, a qualitative assessment of the morphologic appearance of tricuspid valve closure motion during the A-C segment was predictive of right ventricular enddiastolic pressure over the wide range produced by nitroprusside infusion. In addition, it reliably identified patients with elevated end-diastolic pressures. All nine patients had a B plateau or hump in the initial resting tricuspid valve echogram when the right ventricular end-diastolic pressure was 9 mm Hg or greater. Therefore, an analysis of morphologic changes in the tricuspid valve closure motion provides a valuable noninvasive tool for assessing right ventricular end-diastolic pressure at rest and during acute vasodilator therapy in patients with right heart failure.     

Repeat treadmill exercise testing: Variability of results in patients with angina pectoris

To assess the reproducibility and individual variability of ECG treadmill exercise test results, we evaluated 23 patients with coronary artery disease and stable exertional angina by means of two control exercise tests performed on different days within a 1 week period. In addition, each control test was followed on the same day by a single dose of placebo or active agent determined in a randomized double-blind manner and the exercise test was repeated. When the mean exercise test results from the control tests on days 1 and 2 were compared, there was a significant increase in exercise duration to angina (7.4 ± 3.2 to 9.0 ± 3.3 minutes, p < 0.05), ST segment depression (7.8 ± 3.9 to 9.6 ± 3.6 minutes, p < 0.01), and maximal exercise (9.7 ± 3.7 to 11.0 ± 4.1 minutes, p < 0.01). In addition, when the mean exercise results on the control test were compared to those on the postplacebo test on the same day, similar increases in exercise duration were observed at each end point (p < 0.01). Individual differences of more than 2 minutes in exercise duration between the two control tests and between the control and postplacebo tests in time to angina, ST segment depression, and maximal exercise were frequent (26% to 33% of patients). However, the mean rate-pressure products on the two control tests performed on days 1 and 2 and on the control and postplacebo tests performed on the same day did not differ at angina, ST segment depression, and maximal exercise. Therefore, we conclude that patients demonstrate considerable variability in the time to angina, ST segment depression, and maximal exercise but not in rate-pressure product at these end points.     

Miscoding of hospital discharges as acute myocardial infarction: implications for surveillance programs aimed at elucidating trends in coronary artery disease

The current decline in coronary artery disease mortality (CAD) may be a result of a declining population risk or of a declining case-fatality rate. Information on incidence trends for myocardial infarction (MI) could be used to distinguish between these 2 possibilities. Hospital discharge codes for MI (ICDCM-410) could be used as a convenient proxy for incidence trends, provided that coding of hospital discharges is sufficiently accurate. To evaluate the accuracy of medical records coding of patients signed out with an acute MI code (ICDCM-410), we compared them to an independent cardiology surveillance study of all patients with acute MI admitted to a large county teaching hospital. Over a 12-month period, 110 patients were coded as ICDCM-410 by medical records, but only 67 of these were detected by cardiology surveillance. The charts of the 43 patients not detected by surveillance were reviewed. In none of the 43 was evidence of acute MI found. In 28 of the 43, the discharge summaries listed rule out MI or status post-MI readmitted for further diagnostic workup, but were miscoded as ICDCM-410. Twelve of the 43 patients had cardiac arrests but were coded as ICDCM-410, even though there was no evidence of MI. Therefore, erroneous coding of patients as acute MI (ICDCM-410) may conceal a true downward trend in the incidence of CAD.     

Effects of oral quinidine on left ventricular performance in normal subjects and patients with congestive cardiomyopathy.

To evaluate the effects of oral quinidine therapy on left ventricular performance, 10 normal subjects and 8 patients with cardiomyopathy were studied with echocardiography at rest, after intravenous injection of atropine and during infusion with phenylephrine. The echocardiographic studies were performed during oral quinidine therapy and during placebo administration. In the normal subjects heart rate was significantly faster with quinidine than with placebo (74 +/- 8 (standard deviation) versus 68 +/- 9 beats/min, P less than 0.01), but there was no significant change in blood pressure or left ventricular size and performance. After administration of atropine, heart rate was identical with and without quinidine but the mean normalized velocity of left ventricular dimension shortening was significantly less with quinidine than with placebo (1.28 +/- 0.19 versus 1.44 +/- 0.21, P less than 0.01). During acute pressure loading with phenylephrine there was no difference in left ventricular size or performance during quinidine therapy. In the patients with cardiomyopathy, no significant differences in left ventricular function were detected with this protocol during quinidine therapy. It is concluded that oral quinidine therapy appears to have little adverse effect on left ventricular performance at rest or during acute pressure loading.     

Favorable effects of oral maintenance digoxin therapy on left ventricular performance in normal subjects: Echocardiographic study

Left ventricular performance was assessed with echocardiography in 10 normal subjects before and during maintenance therapy with digoxin (0.5 mg/day orally) in the basal state and after acute pressure loading with intravenously administered phenylephrine. During digoxin therapy, despite a decrease in mean heart rate of 5 beats/min in the basal state, mean left ventricular ejection fraction increased from 74 ± 2 to 79 ± 1 percent (standard error, P < 0.03); percent shortening of a left ventricular minor dimension increased from 37 ± 2 to 41 ± 1 percent (P < 0.04) and the mean rate of left ventricular dimension shortening increased from 5.66 ± 0.22 to 6.31 ± 0.23 cm/sec (P = 0.05). During acute pressure loading with phenylephrine there was no change in mean heart rate after digoxin and mean ejection fraction increased from 69 ± 3 to 75 ± 2 percent; mean percent shortening increased from 33 ± 2 to 38 ± 2 percent; mean rate of shortening increased from 5.46 ± 0.32 to 6.48 ± 0.33 cm/sec and mean normalized rate of shortening increased from 1.11 ± 0.06 to 1.29 ± 0.05 sec⁻¹ (all P < 0.01). In a few subjects the response to digoxin did not coincide with the mean data for the whole group. This variability was largely due to difficulties in exactly matching heart rate between the control and digoxin studies. These data (1) support the concept that long-term oral digoxin therapy exerts a positive inotropic effect on the normal left ventricle, and (2) demonstrate the usefulness of echocardiography in noninvasive assessment of the effects of drugs on left ventricular performance.     

Cardiovascular disturbances in chronic respiratory insufficiency

The mechanical factors by which chronic respiratory insufficiency may influence right and left ventricular performance during both spontaneous and mechanical ventilation are reviewed. During a spontaneous inspiration the right heart distends because of increased inflow and increased pulmonary vascular resistance. This decreases the effective left ventricular compliance, through ventricular interdependence, reducing the gradient for pulmonary venous return. The inspiratory decrease in pleural pressure also effectively increases the impedance to left ventricular ejection. An inspiratory increase in abdominal pressure further increases the left ventricular afterload. These factors combine to impair left ventricular performance. During intermittent positive pressure ventilation, left ventricular stroke volume increases early in inspiration. This increased inspiratory flow cannot be attributed to a phase lag in the right heart output reaching the left heart chambers because, even with a constant pulmonary arterial inflow, aortic flow increases during inspiration. Several factors may act in concert to improve left ventricular performance, despite the adverse effects of intermittent positive pressure ventilation on the right ventricle. These include (1) a decrease in right heart volume, increasing left ventricular compliance and hence the gradient for pulmonary venous return; (2) anterograde emptying of the alveolar capillary bed with lung inflation; (3) the increase in pleural pressure decreasing impedance to left ventricular emptying; and (4) physical compression of the heart by the lungs.     

Role of parietal pericardium in acute, severe mitral regurgitation in dogs

Mitral regurgitation (MR) resulting from acute disruption of the mitral valve apparatus leads to serious hemodynamic sequelae. The lesion produces major elevation of left atrial (LA) and pulmonary artery pressures and decreases forward cardiac output. Clinical studies have shown hemodynamic patterns in acute MR similar to those seen in constrictive pericardial disease, suggesting that the pericardium serves to importantly limit cardiac filling in this condition. This hypothesis has not been tested in an animal model in which the intrapericardial pressure can be directly measured. In the present study intrapericardial and intracardiac pressures were measured in 8 dogs before and after the production of acute MR. After production of MR, mean LA pressure increased from 8 +/- 3 to 20 +/- 7 mm Hg (p = 0.004) and the peak LA V wave averaged 31 +/- 13 mm Hg. Mean right atrial pressure increased slightly, from 4 +/- 2 to 5 +/- 1 mm Hg (p less than 0.008). Intrapericardial pressure increased in each dog, but the increment was invariably small (1 +/- 2 to 3 +/- 2 mm Hg, p = 0.001) and there was no tendency to equalization of pressure between right- and left-sided cardiac chambers. Thus, the role of the pericardium in the immediate hemodynamic response to acute, severe MR is minor.     

Attenuation of coronary vascular resistance by selective alpha 1-adrenergic blockade in patients with coronary artery disease

Alpha-adrenergic-mediated coronary vasoconstriction during stress such as cold pressor testing may contribute to myocardial ischemia by increasing coronary vascular resistance in patients with severe coronary artery disease. Nonselective alpha-receptor blockade with phentolamine abolishes both the peripheral and coronary vasoconstriction during cold pressor testing, but causes reflex tachycardia and increased inotropy. To determine the role of selective alpha 1-receptor blockade, the changes in coronary vascular resistance during cold pressor testing were measured in 18 patients with coronary artery disease before and after intravenous administration of 100 mg of trimazosin. Cold pressor testing was performed at a constant paced subanginal heart rate of 95 +/- 5 beats/min (+/- 1 SD). Before trimazosin, cold pressor testing increased mean arterial pressure by 9 +/- 4% (102 +/- 14 to 111 +/- 14 mm Hg, p less than 0.001) with no change in coronary sinus blood flow, but significantly increased coronary vascular resistance by 15 +/- 19% (1.02 +/- 0.46 to 1.15 +/- 0.57 units, p less than 0.05). Five minutes after trimazosin, cold pressor testing increased mean arterial pressure by 6 +/- 5% (p less than 0.001) with a marked attenuation of the increase in coronary vascular resistance (6 +/- 11%, p = NS), which was significantly less than before trimazosin (p less than 0.02). Trimazosin did not increase plasma norepinephrine concentration at rest, suggesting that in the dosage used trimazosin caused selective alpha 1-receptor blockade.(ABSTRACT TRUNCATED AT 250 WORDS)     

Beneficial hemodynamic effects of intravenous and oral diltiazem in severe congestive heart failure

Concern persists about the potential negative inotropic effects of calcium channel blockers in patients with severely depressed myocardial function. Therefore, intravenous diltiazem (100 to 200 micrograms/kg per min infusion) was administered for 40 minutes followed by oral diltiazem (90 to 120 mg/8 hours) for 24 hours to patients with advanced congestive heart failure (New York Heart Association class III to IV, mean ejection fraction 26 +/- 4 [SD]). Intravenous diltiazem (eight patients) increased cardiac index 20% (2.05 +/- 0.8 to 2.47 +/- 0.8 liters/min per m2, p less than 0.01), stroke volume index 50% (22 +/- 9 to 33 +/- 12 ml/m2, p less than 0.001) and stroke work index 27% (19 +/- 10 to 24 +/- 10 g-m/m2, p less than 0.05); while reducing heart rate 23% (97 +/- 18 to 75 +/- 11 beats/min, p less than 0.01), mean arterial pressure 18% (95 +/- 13 to 78 +/- 7 mm Hg) and pulmonary wedge pressure 34% (29 +/- 9 to 19 +/- 7 mm Hg), without altering maximal first derivative of left ventricular pressure (dP/dtmax). Oral diltiazem (seven patients) produced equivalent hemodynamic effects. Transient junctional arrhythmias were observed in three of eight patients with intravenous diltiazem and one of seven patients with oral diltiazem. It is concluded that intravenous and short-term oral diltiazem improve left ventricular performance and reduce myocardial oxygen demand by heart rate and afterload reduction without significantly depressing contractile function in severe congestive heart failure. Caution should be exercised to avoid potential adverse, drug-induced electrophysiologic effects in such patients.     

Comparative study of available medical therapy for hypercalcemia of malignancy

The relative efficacy of five drugs in the treatment of hypercalcemia of malignancy was assessed in a randomized study. The drugs were oral phosphate, mithramycin, glucocorticoids, indomethacin, and ethane-1-hydroxy-1, 1-diphosphonate (EHDP). No single agent was universally effective. Oral phosphate and mithramycin were the most efficacious, each producing a decrease in serum calcium concentrations in four of five patients, although there were serious disadvantages with the use of each. Glucocorticoids were effective in only two of five patients who received randomized treatment. A further five patients received nonrandomized treatment with glucocorticoids, and only three of these showed response. Indomethacin was effective in only one of five patients to whom it was given, and EHDP was effective also in only one of five patients. The new diphosphonate, 3-amino-1-hydroxypropane-1, 1-diphosphonate (APD) was evaluated in the treatment of hypercalcemia in 13 patients with malignant disease and two with primary hyperparathyroidism. APD caused a significant decrease in serum calcium concentration in nine of 12 patients within 72 hours. These results indicate that there is no currently available pharmacologic agent that is entirely satisfactory in the treatment of hypercalcemia. The most effective agents were mithramycin, oral phosphate, and APD. Glucocorticoids and orally administered EHDP showed limited effectiveness, and indomethacin was ineffective in the majority of patients.     

Positive inotropic and vasodilator effects of MDL 17,043 in patients with reduced left ventricular performance

To assess the potential positive inotropic properties of the drug MDL 17,043, 10 patients were studied who had impaired left ventricular (LV) performance and who were undergoing diagnostic cardiac catheterization (LV ejection fraction 16 to 46%). MDL 17,043 was given in repeated i.v. doses of 0.5 mg/kg every 15 minutes until a maximal effect was observed or a total dose of 3 mg/kg was attained. Cardiac output increased from 3.5 +/- 1.0 to 5.3 +/- 0.7 liters/min (p less than 0.005); pulmonary artery wedge pressure decreased from 22 +/- 4 to 9 +/- 5 mm Hg (p less than 0.001); and total systemic resistance decreased from 2,335 +/- 1,147 to 1,310 +/- 365 dyne cm-5 (p less than 0.025). Also, maximal LV dP/dt increased from 1,011 +/- 301 to 1,243 +/- 330 mm Hg/s (p less than 0.001). No significant changes in heart rate, systemic blood pressure, routine blood chemistries, complete blood counts or platelet counts were observed. Thus, MDL 17,043 has hemodynamic effects consistent with positive inotropic and vasodilating properties in patients with reduced LV performance. Because this agent is effective orally, further evaluation in patients with overt congestive heart failure is warranted.     

Noninvasive diagnosis of aortic and mitral valve disease with pulsed-doppler spectral analysis

To differentiate normal from abnormal left-sided heart valves, 34 adults (6 normal and 28 abnormal) with 48 valve lesions proved at catheterization were examined using a 3 MHz duplex pulsed Doppler echocardiograph with 2-dimensional verification of sample volume position and on-line display of the Doppler audio spectrum. A uniform protocol was used to position the sample volume for each lesion and to analyze the Doppler spectral data. Intracardiac blood turbulence, manifested by an increased Doppler spectral envelope area, was the noninvasive indicator of disease. The specific lesion present was determined by documenting the intracardiac location and timing of the turbulence. Doppler spectral envelope areas in all normal valve sites were smaller than those measured at the same sites in patients with aortic stenosis, mitral stenosis, and mitral regurgitation (p < 0.01). Except for a single patient with minimal aortic regurgitation, spectral envelope area allowed complete separation of patients with valve disease from normal subjects (p < 0.01). High sensitivity (97%) and specificity (100%) were noted despite the presence of multiple valve lesions in 67% of the patients. The data demonstrate application of a simple, noninvasive method of acquiring and analyzing Doppler echocardiographic data which allows accurate identification or exclusion of left-sided valve disease in adults, even in the presence of multiple valve lesions.     

Association between human tumor colony-forming assay results and response of an individual patient's tumor to chemotherapy

An in vitro tumor colony-forming assay was utilized to measure the sensitivity of 800 individual patients' tumors to a variety of antineoplastic agents. Thirty-six separate histologic types of cancer were represented. Only 199 of the 800 patients' tumors (25 percent) both formed colonies in vitro and had enough cells in the biopsy or fluid specimen to perform drug sensitivity assays. In 123 instances the drug tested in vitro against the tumor was also used clinically to treat the patient. The clinician caring for the patient did not know the results of the in vitro test. When analyzed in a retrospective manner, the probability of a positive prediction from the assay, given the patient responded clinically, was 0.88. The probability for a negative prediction of the assay given the patient did not respond, was 0.94. Associations of in vitro and in vivo results in the 123 correlations were highly significant (p < 0.001). We conclude that, as now constituted, the human tumor colony-forming assay can provide useful sensitivity information for only about 25 percent of the general oncology patients. Secondly, a prospective clinical trial of the assay is needed to insure that the assay is indeed predictive of which drug will produce a patient response and that it is not merely an indicator that a particular patient's tumor is highly responsive in vivo.     

Minimal-change lesion nephrotic syndrome with renal oncocytoma

A renal mass was found in a 49-year-old man presenting with idiopathic nephrotic syndrome. The excised tumor was a well-encapsulated renal oncocytoma. Examination of the kidney revealed a minimal-change glomerular lesion and moderate arterionephrosclerosis. Nephrotic range proteinuria persisted through a postoperative course of prednisone therapy, but diminished and cleared within the subsequent two-year period. Renal function has remained stable and proteinuria has not recurred over a four-year follow-up. The clinical course suggests a previously unreported relationship between renal oncocytoma and minimal-change lesion nephrotic syndrome.     

Cervical fracture complicating ankylosing spondylitis: A report of eight cases and review of the literature

Fracture of the cervical spine is a serious and often fatal complication of ankylosing spondylitis. An evaluation of eight patients and a review of 75 additional cases from the literature are presented. Although this complication is relatively uncommon, it is clear that people with advanced disease and complete ankylosis of the cervical spine are at increased risk of sustaining cervical fracture. When fracture occurs it usually stems from minor trauma resulting most commonly in disruption of the lower cervical segments (fifth through the seventh cervical vertebrae). Fracture is most likely the result of a hyperextension type injury, occurs through what was formerly an intervertebral space, and is unstable. Severe neurologic sequelae occur in 57 percent of the cases and the mortality rate (35 percent) is twice that observed with similar fracture involving normal spines. The majority of patients are best treated with closed reduction with halo traction together with body cast or jacket. Laminectomy is rarely indicated except in the event of an advancing neurologic deficit. With appropriate understanding and execution of management principles, the outcome in these patients can be favorable. Unfortunately, recognition of cervical fracture in patients with ankylosing spondylitis is often needlessly delayed. Distortion of normal anatomy in spondylitics, predominant fracture location in lower cervical spine segments and lack of obvious displacement make identification difficult. Thus, management is often inappropriate resulting in exessive neurologic injury and mortality.