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The magnitude of acute arrhythmogenicity of doxorubicin administration has not been characterized. In this study the type and frequency of cardiac arrhythmia is determined in the first hour and first 24 hours following doxorubicin given as a 10-minute infusion. Twenty-nine patients with diverse malignancies were studied with Holter monitors on 33 postdoxorubicin days. Control recordings were made on days remote from doxorubicin treatment. The frequency of arrhythmia that could be attributed to doxorubicin was low: 3% of studies in the first hour postinfusion and 24% of studies in 1 to 24 hours postinfusion. The most commonly seen arrhythmia was an increased frequency of ventricular premature beats. Arrhythmia following doxorubicin infusion is rare in the first hour and more common in the remainder of the first 24 hours postinfusion. There are no acute or long-term adverse consequences related to the appearance of arrhythmia due to doxorubicin.

In trypanosomes and related kinetoplastida a common short 5' leader sequence is encoded by the highly repetitive mini-exon gene and added to all protein coding mRNAs by trans-splicing. To initiate a search for transcription factors associated with transcription of the mini-exon we have used an electrophoretic mobility shift assay to detect trypanosome nuclear factors which interact specifically with mini-exon DNA. A factor present in the nuclei of both infectious bloodstream forms and non-infectious culture forms of Trypanosoma brucei was shown by DNAase I footprinting and oligonucleotide competition to bind 5' to the transcription start site of the mini-exon. A second factor which bound to the mini-exon itself at a sequence conserved in other kinetoplastida was evident only in the nuclei of infectious bloodstream forms.

When bypass graft surgery is planned, it is appreciated that sequential coronary artery stenoses often entrap the origins of arterial branches that have a significant, but subgraftable, diameter. These branches are routinely not perfused by saphenous vein grafts implanted beyond the second lesion. Data are presented on improving perfusion of such branches in 26 patients by the technique of retrograde intraoperative balloon-catheter dilatation. During coronary artery surgery, specially designed angioplasty catheters, 2 to 3 mm in diameter, were introduced through the coronary arteriotomy and passed retrogradely across the distal lesion. Balloon inflation was performed two to four times at 4 to 7 atm. Lesion size was assessed before and after angioplasty with the use of graduated coronary probes. Probe-determined lesion diameter increased from 1.1 +/- 0.4 to 2.0 +/- 0.4 mm (percent increase, 109 +/- 8). In selected patients, intraoperative balloon-catheter dilatation is a promising technique adjunctive to coronary surgery. Clinical significance and long-term effectiveness of this procedure require further evaluation.

Myocardium salvaged by early thrombolysis and then perfused through a residual stenosis may be at risk for ischemic events. To investigate this possibility, the short-term (2-week) clinical course of 81 consecutive patients managed within a randomized intracoronary thrombolysis trial was reviewed. All patients underwent coronary angiography within 5 hours of symptoms of acute myocardial infarction and were stratified into the following 3 outcome groups: patients with initially subtotal occlusion (subtotal group, n = 17), those with initial total occlusion and infarct artery reperfusion (reperfused group, n = 24) and those with continued infarct artery occlusion (occluded group, n = 40). Recurrent ischemic events were defined as spontaneous typical angina, provokable angina on predischarge exercise testing, and reinfarction. Eleven of 17 patients (65%) in the subtotal and 11 of 23 patients (48%) in the reperfused groups had an ischemic event (difference not significant). In contrast, 4 of 37 patients (11%) with occlusion had an ischemic event (p less than 0.01 compared with patients in the subtotal or reperfused groups). Four patients were excluded because of early (within 72 hours) elective coronary bypass surgery or death from pump failure. To eliminate the impact of multivessel coronary artery disease (CAD), 39 patients with 1-vessel CAD were analyzed separately. Five of 9 patients (56%) in the subtotal group, 3 of 10 (30%) in the reperfused group and only 2 of 20 (10%) in the occluded group had an ischemic event. These observations suggest the need for a more definitive revascularization strategy for acute myocardial infarction.

The rationale for the therapy of acute myocardial infarction is logically based upon recognition of the etiologic role of acute thrombosis; hence the primary therapeutic goal is to restore coronary artery patency (and subsequently to preserve that patency). Multiple thrombolytic drugs are variably successful in accomplishing that objective as, in special circumstances, are acute mechanical interventions. After reperfusion, additional strategies are advocated both to preserve patency and to enhance the benefit of reperfusion. The state of our current understanding has been achieved through a productive combination of individual observations and inventiveness as well as painstaking clinical trials. While the major questions now appear to have satisfactory answers, numerous secondary questions have been generated in an effort to further refine the therapeutic algorithms as well as possibly expand the indications to a wider cohort of patients than have been traditionally treated and/or studied to date.

Fifty-five patients with acute myocardial infarction evaluated within 4 hours of the onset of symptoms were entered into an angiographically controlled trial of intracoronary streptokinase (IC STK). Forty-three patients with total occlusion of their infarct artery were randomized to either IC STK or intracoronary nitroglycerin (IC NTG), and 12 patients with less-than-complete occlusion received only IC NTG. Reperfusion of a totally occluded vessel was achieved in 69% of STK patients and 17% of IC NTG patients. Time from onset of symptoms to peak CK activity was significantly shorter in reperfused patients and patients with subtotal occlusion on initial angiography than in patients with total occlusion who were not reperfused (p less than 0.0001). Comparison of radionuclide ejection fractions (EF) determined acutely and 10 to 14 days after infarction failed to show improvement in either the STK or IC NTG group (mean decrease of 2.8% and 0.4%, respectively). In contrast, patients with subtotal occlusion on baseline angiography demonstrated a significant (p = 0.05) spontaneous improvement in EF over 2 weeks (7.3% increase).

We have previously shown the presence of various purine salvage enzymes in Trypanosoma cruzi, including phosphoribosyltransferase, aminohydrolase, kinase, phosphorylase and hydrolase activities. We now report that a similar situation occurs in Leishmania mexicana amazonensis and Trypanosoma brucei brucei. In all three organisms we found higher levels of activity for the phosphoribosyltransferase enzymes than for the nucleoside kinases, suggesting a preference for the salvage of purine bases rather than nucleosides. Similarly, absence of inosine phosphorylase activity suggests that only one route for the salvage of hypoxanthine is available to the three organisms. The most striking difference was that whereas T. cruzi and T. brucei possessed adenosine aminohydrolase activity, this was not detected in L. mexicana; instead adenine aminohydrolase activity was found. The overall similarity, as judged by the distribution of enzyme activities, of purine salvage in these three members of the kinetoplastida suggest a broad spectrum of activity for any inhibitor acting in this area; the plethora of alternative salvage pathways, however, suggests that in no case would such inhibition be cidal.

The prevalence of cardiac abnormalities in the spectrum of human immunodeficiency virus (HIV) infection is unknown. Sixty consecutive HIV-infected patients were studied using echocardiograms, electrocardiograms (50 patients) and ambulatory electrocardiographic monitoring (43 patients). Group A (25 patients) were seropositive but pre-AIDS, whereas group B (35 patients) had AIDS and included 24 with an active opportunistic infection (group B1) and 11 without it (group B2). Abnormalities were identified in 32 of 60 patients (53%) and were more frequent in group B (23 of 35, 66%) than in group A (9 of 25, 36%, p less than 0.05) but independent of active opportunistic infection (15 of 24, 62%, in group B1 vs 8 of 11, 73%, in group B2). Echocardiographic abnormalities were identified in 21 of 60 patients (35%), including 7 of 25 (28%) in group A vs 14 of 35 (40%) in group B (difference not significant), and 7 of 24 (29%) in group B1 vs 7 of 11 (64%) in group B2 (difference not significant). Those patients with an absolute CD4 lymphocyte count less than or equal to 100/mm3 had a higher prevalence of echocardiographic abnormalities (12 of 22) than those with CD4 counts greater than 100/mm3 (1 of 14, p less than 0.01). Left ventricular dilation or hypokinesis was identified in 14 of 60 patients (23%), including 4 of 25 (16%) in group A and 10 of 35 (29%) in group B. Electrocardiographic abnormalities were seen in 22 of 50 patients (44%) including 5 of 18 (28%) in group A and 17 of 32 (53%) in group B (difference not significant).(ABSTRACT TRUNCATED AT 250 WORDS)

We have developed a computer graphics program system for the schematic representation of several protein secondary structure analysis algorithms. The programs calculate the probability of occurrence of alpha-helix, beta-sheet and beta-turns by the method of Chou and Fasman and assign unique predicted structure to each residue using a novel conflict resolution algorithm based on maximum likelihood. A detailed structure map containing secondary structure, hydrophobicity, sequence identity, sequence numbering and the location of putative N-linked glycosylation sites is then produced. In addition, helical wheel diagrams and hydrophobic moment calculations can be performed to further analyze the properties of selected regions of the sequence. As they require only structure specification as input, the graphics programs can easily be adapted for use with other secondary structure prediction schemes. The use of these programs to analyze protein structure-function relationships is described and evaluated.

Recent studies suggest that apolipoproteins and subfractions of high-density lipoprotein (HDL) cholesterol may be better predictors of atherosclerotic coronary artery disease (CAD) than are plasma cholesterol and total HDL cholesterol. To examine this hypothesis, plasma cholesterol and triglyceride, cholesterol of low-density lipoprotein, HDL and its subfractions 2 and 3, apolipoprotein A-I, the apolipoprotein B of low-density lipoprotein, the ratio of apolipoprotein EII to EIII, and ratios of several of these variables were measured in a selected series of 126 patients (83 men and 43 women) who underwent coronary angiography for suspected CAD. Mean values of many of these variables differed significantly between the men with CAD and the men without significant CAD, when controlled for age, use of beta blockers and diuretic drugs. Using multivariate logistic regression analysis, the only variable that made a significant independent contribution in predicting CAD in men was the ratio of HDL cholesterol to total plasma cholesterol (p less than 0.0001). The mean of this ratio was 0.17 +/- 0.01 mg/dl in the men with CAD and 0.23 +/- 0.02 mg/dl in the male controls. All men with ratios of less than 0.15 mg/dl had significant CAD, defined as 50% or greater luminal diameter narrowing of 1 or more of the major coronary arteries. No measurement was a significant univariate or multivariate predictor of CAD in the women, but the power to detect such predictors was reduced because of small group sizes. In conclusion, the ratio of HDL cholesterol to plasma cholesterol may be superior to many of the more recently described lipoprotein and apolipoprotein-derived predictors of CAD.

Clinical and necropsy findings are described in three patients who had angina pectoris at rest, S-T segment elevation on electrocardiography during chest pain, coronary arterial spasm on angiography and sudden death. Although significant "fixed" coronary narrowing (that is, narrowing due to atherosclerotic plaques) was appreciated by angiography in only one of the three patients, necropsy disclosed in all three patients severe fixed coronary narrowings involving particularly the artery in which spasm had been demonstrated during life. Additionally, examination of each 5-mm long segment of the coronary artery that had been spastic during life (two patients) disclosed several focally spastic segments at necropsy, indicating that spasm persisted after death. Although most previously described necropsy patients with Prinzmetal's angina had some fixed coronary narrowing, underlying fixed narrowing may be difficult to identify angiographically as demonstrated by the three patients in this study.

Aortic wall echocardiograms were obtained simultaneously with pulmonary artery wedge pressures (PAWP) in 21 patients free of obstructive mitral valve disease. There was a significant (p < 0.001) negative correlation between the fraction of passive posterior aortic wall motion occurring in the first third of diastole (the atrial emptying index--AEI) and the pulmonary artery wedge pressure (r = -0.91). The AEI for patients with normal PAWP (less than or equal to 12 mm. Hg) was 0.94 +/- 0.06 (mean +/- S.D.) compared with 0.61 +/- 0.20 for those with abnormal PAWP (> 12 mm. Hg). No patient with a normal PAWP had an AEI < 0.80, and no patient with a PAWP > 18 mm. Hg had an AEI > 0.66. These data suggest that analogous to the reported use of the AEI to estimate severity of mitral obstruction, the index provides a noninvasive measure of left ventricular filling pressure when the mitral valve is normal.

Digital subtraction left ventriculography using intravenous contrast injection was evaluated as a screening diagnostic method for coronary heart disease. Intravenous ventriculography was performed in 61 patients with 35 cc of contrast medium injected into a central vein (usually the inferior vena cava). Recognition of regional wall motion abnormalities by this technique was shown to be comparable with direct left ventriculography in 40 patients who underwent both imaging modalities at rest. If the rest digital ventriculogram was normal, it was repeated after incremental atrial pacing to the onset of chest pain or to a maximal heart rate of 150 beats/min. Forty-four of the 61 patients had significant coronary artery disease, of whom 10 had a wall motion abnormality at rest on intravenous ventriculography. With pacing, 28 of the 34 remaining patients developed a new wall motion abnormality. Thus, 38 (86%) of 44 patients with coronary heart disease were identified by wall motion abnormalities. One of the 17 patients without coronary artery disease had an abnormal rest study and was incorrectly assigned a diagnosis of coronary disease. Intravenous digital ventriculograms approximate those obtained by direct ventriculography. When combined with atrial pacing they are a sensitive and specific means of detecting coronary artery disease.

To better characterize the changes in left ventricular ejection fraction after myocardial infarction, we compared radionuclide ventriculograms obtained acutely and 2 weeks after acute myocardial infarction in 40 patients. These patients underwent angiography within a mean of 4 hr and 20 min after the onset of symptoms of infarction and either received no therapy (32 patients who were control subjects in a thrombolysis trial) or did not experience reperfusion (eight patients) despite receiving streptokinase infusions. In all 40 patients, the change in left ventricular ejection fraction over 2 weeks was small (+2.6%). Patients were then grouped according to the presence or absence of residual flow on their angiograms. Residual flow was considered to be present in 21 patients, in 12 by virtue of subtotal occlusion of the artery supplying the area of infarct and in nine because of well-developed coronary collaterals to the distal infarct artery. Mean change in ejection fraction for patients with residual flow was +6.9 +/- 2.3% vs -2.2 +/- 1.7% for patients without residual flow (p less than .01). Fourteen of 21 (67%) patients with residual flow had a spontaneous rise in ejection fraction of greater than 5%, as compared with two of 19 (11%) patients without residual flow (p less than .01). Time to peak level of creatine kinase (CK) was significantly shorter in the residual flow group (15 vs 23 hr, p less than .01), while the peak level of CK was lower (1550 vs 2220 IU) in these patients. This latter difference did not reach statistical significance (p = .10).(ABSTRACT TRUNCATED AT 250 WORDS)

The long-term prognostic implications of the electrocardiographic location of a myocardial infarction and the subsequent retention or disappearance of diagnostic Q waves were examined in patients enrolled in the Aspirin Myocardial Infarction Study (AMIS). The 4524 participants, ages 30-69 years, had sustained a myocardial infarction 8 weeks to 60 months before randomization to aspirin and placebo groups. Subjects were followed for at least 3 years (average 38.2 months). Using the Minnesota Code, myocardial infarctions were classified according to three electrocardiographic locations: lateral, inferior and anterior, with further subdivision into major, moderate and minor criteria based on Q-wave duration and Q/R rations. Total mortality was not significantly different among patients with single infarct sites: lateral 11.8%, inferior 8.0% and anterior 9.4%. Patients with multiple electrocardiographic infarct locations had a significantly higher mortality (14.6%, p less than 0.0002). Participants with Minnesota Code major criteria of infarction also had a significantly higher mortality (10.6%) than those with moderate (7.2%) or minor (7.4%) criteria (p less than 0.01). Loss of a previously documented diagnostic Q wave occurred in 14.2% of participants. Mortality among patients who lost Q waves (6.5%) was not significantly different from that among those with persistent Q waves in a single infarct location (8.7%). No long-term prognostic significance can be attributed to the site of infarction or loss of Q wave on the resting ECG. However, major Q-wave criteria and extent of infarction based on multiple coded sites are associated with a higher 3-year mortality.