William Strauss

A Comparison of Quality of Life Scores in Patients With Angina Pectoris After Angioplasty Compared With After Medical Therapy Outcomes of a Randomized Clinical Trial

Background Evaluations of therapy for the treatment of angina have traditionally consisted of a combination of objective measures, such as exercise tolerance, and subjective markers, such as angina attack rate. Recently, the need to assess how patients feel-their quality of life (QOL)-has been regarded with increasing importance. Standard instruments are available to assess QOL and its change after therapeutic intervention. Although QOL instruments have been used to assess the efficacy of percutaneous transluminal coronary angioplasty (PTCA), they have not been used previously to compare the impact of PTCA with that of medical therapy in patients with angina pectoris. We report on the changes in self-assessed QOL among patients randomly assigned to treatment by PTCA or medical therapy and relate these measurements to changes in exercise performance and coronary angiograms. Methods and Results Patients with stable angina, a positive exercise tolerance test, and at least 70% stenosis (index lesion) in the proximal two thirds of one major coronary artery were randomly assigned to receive PTCA or medical therapy. Six months after randomization, each patient underwent repeat exercise testing and coronary angiography. Before randomization and at the 6-month visit, patients completed a self-administered QOL questionnaire that measured physical functioning and psychological well-being. We compared the changes in QOL with changes between the baseline and 6-month exercise tests, stratified by terciles (decrease in duration, 0- to 2-minute increase, and >2-minute improvement). We also stratified patients by whether there was more or less than 2 SD change (18.8%) in diameter stenosis of the index lesion (initial minus follow-up angiogram), and we related these to changes in QOL measures. One hundred eighty-two patients with one-vessel disease completed baseline and 6-month questionnaires. At baseline, there were no differences in any QOL measurements between treatment groups. At the 6-month follow-up visit, there was greater improvement in both physical functioning and psychological well-being scores for patients receiving PTCA (+7.36±15.6, PTCA ; +1.98±14.7, medical therapy; P<.02). Improvement in QOL variables was noted only in patients demonstrating an increase in exercise performance. Also, patients assigned to either treatment whose angiograms demonstrated more than 18.8% improvement in index lesion percent stenosis experienced a significant increase in their QOL scores. Conclusions This was the first study of the relative changes in QOL measures assessed with the use of previously validated and standardized instruments in patients randomly assigned to treatment with PTCA or medical therapy. Patients assigned to PTCA demonstrated a significantly greater improvement in both physical and psychological measures. This improvement was noted in patients whose exercise performance improved and whose angiograms demonstrated an improvement in lesion severity. (Circulation. 1995 ;92 :1710-1719.)

Safety and efficacy of diltiazem hydrochloride for the treatment of stable angina pectoris: Report of a cooperative clinical trial

Sixty-three patients completed a multicenter 10 week, double-blind, parallel group protocol evaluating the efficacy of diltiazem versus placebo with respect to rate of attacks of angina, nitroglycerin consumption and duration of treadmill exercise. An additional 36 patients were evaluated for drug safety. A 4 week placebo lead-in phase was followed by a 2 week dose titration period and two treatment evaluation periods of 2 weeks each. Both diltiazem and placebo were associated with a significant reduction in weekly frequency of angina from the baseline rate. Intergroup comparison disclosed a significantly greater reduction for the patients receiving diltiazem than for those receiving placebo. A similar reduction was noted for nitroglycerin consumption. Total exercise duration at week 10 was statistically greater in patients treated with diltiazem. Diltiazem was well tolerated. No abnormalities in hematologic profiles or in routine serum chemistry values were observed; electrocardiographic P-R and QRS intervals were unaffected. Adverse effects that could have been related to drug administration were reported in 11 patients who received diltiazem and in 12 patients who received placebo. Of the 17 episodes in the diltiazem group only 3 were considered significant and drug-related, and only one of these resulted in discontinuation of the drug.

Safety and efficacy of intravenousdiltiazem in atrial fibrillation or atrial flutter

This study examines the efficacy of various doses of intravenous diltiazem to control the ventricular response during atrial fibrillation or atrial flutter. Control of the ventricular response of patients with atrial fibrillation and a rapid ventricular response can provide patients with relief of symptoms and improve hemodynamics. Eighty-four consecutive patients with atrial fibrillation or atrial flutter, or both, received an intravenous bolus dose of diltiazem followed by a continuous infusion of diltiazem at 5, 10, and 15 mg/hour. The mean ventricular response and blood pressure were monitored. Overall, 94% of patients (79 of 84) responded to the bolus dose with a > 20% reduction in heart rate from baseline, a conversion to sinus rhythm, or a heart rate < 100 beats/min. Seventy-eight patients received the continuous infusion. After 10 hours of infusion, 47% of patients (confidence interval [CI]: 36%, 59%) had maintained response with the 5 mg/hour infusion, 68% (CI: 57%, 79%) maintained response after the infusion was titrated to 10 mg/hour, and 76% (CI: 66%, 85%) after titration from the 5 and 10 mg/hour infusion to the 15 mg/hour dose. For the 3 diltiazem infusions studied, mean (+/- SD) heart rate was reduced from a baseline value of 144 +/- 14 beats/min to 98 +/- 19, 107 +/- 25, 107 +/- 22, 101 +/- 22, 91 +/- 17, and 88 +/- 18 beats/min at infusion times 0, 1, 2, 4, 8, and 10 hours, respectively. By the end of the infusion, 18% of patients (14 of 78) had conversion to sinus rhythm.(ABSTRACT TRUNCATED AT 250 WORDS)

Combined Use of Calcium-Channel and Beta-Adrenergic Blockers for the Treatment of Chronic Stable Angina: Rationale, Efficacy, and Adverse Effects

During the past decade, the therapy for stable angina pectoris has greatly expanded with the introduction of the calcium-channel blockers. Initially studied as monotherapy, these agents have been regularly used in combination with other antianginal medications, most notably the beta-adrenergic blockers. Although there are pharmacologic rationales for combining these agents, in daily practice, the major impetus for combination therapy is continuing angina during monotherapy. At least one well-conducted double-blind study was done to confirm that diltiazem, verapamil, and nifedipine each can markedly improve both subjective and objective measures of efficacy when used in combination with a beta-blocker. However, individual patient responses are of chief importance. Many persons do better with monotherapy than with combination treatment. The offsetting hemodynamic effects of nifedipine and a beta-blocker generally work well together; however, minor side effects are not infrequent. In the patient with underlying conduction system disease, this combination is clearly preferable. Diltiazem with a beta-blocker is usually well-tolerated, with a low incidence of adverse effects, similar to the experience with diltiazem monotherapy. Verapamil in conjunction with a beta-blocker warrants the greatest concern; approximately 10% to 15% of patients will have significant bradycardia, heart block, hypotension, or congestive failure. When these agents are used concurrently, reduced dosages, especially of the beta-blocker, will likely result in a lower incidence of adverse effects with maintained efficacy.

Echocardiography in acute and remote myocardial infarction

Two dimensional echocardiography is just beginning to be used to characterize cardiac damage in patients with acute myocardial infarction. The two dimensional approach allows for a more comprehensive evaluation of cardiac anatomy and is able to detect with high sensitivity changes in regional wall motion that previously were sometimes missed or only found with difficulty using M mode echocardiography. Two dimensional echocardiography appears to offer a basis for quantifying the extent of myocardial damage in acute myocardial infarction and thus may permit objective assessment of therapeutic modalities and prognosis. In addition, the technique facilitates recognition of specific complications in acute myocardial infarction. In particular, the technique offers te ability to distinguish true from false ventricular aneurysm, postinfarction ventricular septal defect from papillary muscle dysfunction and rupture, and right ventricular infarction from cardiac tamponade.

Relationship of the genes for Chediak-Higashi syndrome (beige) and the T-cell receptor [gamma] chain in mouse and man

The genetic linkage of Chediak-Higashi syndrome and its murine analog, beige (bg), to the T-cell receptor (TCR-gamma) gamma chain gene is further defined. Previous studies using recombinant inbred strains of mice demonstrated that the murine bg gene is genetically linked to a murine TCR-gamma gene. We report that in the mouse the frequency of recombination between these two markers is 0.025. Further, we tested the hypothesis that these two genes are linked in the human genome by analyzing restriction fragment length polymorphisms (RFLPs) in five families with children afflicted with Chediak-Higashi syndrome. In three families, RFLPs in TCR-gamma genes were inherited discordantly from Chediak-Higashi syndrome, demonstrating nonlinkage. We postulate that there is an evolutionary chromosomal breakpoint between the bg gene and the TCR-gamma gene.

An Ia-positive mouse T-cell clone is functional in presenting antigen to other T cells

In this report we present data demonstrating the endogenous expression of I-region associated (la) antigens on a cloned line of mouse T cells, CTLL, as well as transcription of the invariant chain gene in these cells. We demonstrate further that this Ia-bearing T-cell clone, CTLL, can utilize the expressed la molecules to present antigen to la-restricted antigen-specific T cells.

Tissue factor pathway inhibitor (TFPI) activity in uremic patients during hemodialysis

We studied tissue factor pathway inhibitor (TFPI) activity during hemodialysis in 10 uremic patients who were not receiving anticoagulant for at least 120 minutes. TFPI activity before dialysis was normal (patients 107 +/- 5.8%, controls 104 +/- 4.5%). During extracorporeal circuit it rose progressively with a statistically significant difference, reaching a plateau between 60 and 120 minutes. Since thrombin induces a marked redistribution and release of TFPI from stimulated endothelial cells and platelets contain about 10% of TFPI activity that is secreted following activation it is possible that thrombin-induced release of TFPI by endothelium and platelets could account for the increased TFPI we found during hemodialysis. To investigate this possibility we measured during dialysis beta-thromboglobulin (beta-TG), thrombin-antithrombin complex (TAT) and prothrombin fragment 1.2 (F 1.2). The increased levels of beta-TG, TAT and F1.2 we noted during extracorporeal circuit are in keeping with this concept. One hundred eighty minutes after initiation of dialysis, by which time all patients were receiving heparin there was a further increase in TFPI (to more than 200% of baseline), due to the presence of the glycosaminoglycan. This was due the previously reported displacement by heparin of the major intravascular pool of TFPI, from endothelial cell surfaces.

Radioimmunolocation of Hepatic and Pulmonary Metastasis of Human Colon Adenocarcinoma

We have established a large library of monoclonal antibodies against a human hepatoma cell line called FOCUS. One such monoclonal antibody (SF-25) detects a 125-kilodalton cell surface antigen found on FOCUS cells. As both the liver and the colon are of endodermal origin, we examined the possibility of expression in colon adenocarcinomas. This antigen was found in all 23 colon adenocarcinoma tissues surgically obtained but was absent in the adjacent normal mucosal counterpart as determined by a direct radioimmunohistologic technique. In the present study, we have established a model for human metastatic colon adenocarcinoma using the LS 180 cell line. Athymic mice were further immunosuppressed by intravenous injection of anti-NK cell antibodies (antiasialo GM1). After 24 h, mice were injected with LS 180 cells either via the tail vein or into the spleen followed by splenectomy. Macroscopic pulmonary and lymphatic metastasis developed within 2-3 wk after injection of cells and 9 of 10 mice died with advanced metastatic disease 2-3 wk later. In addition, macroscopic hepatic metastases were evident in 4 of 5 mice 3-4 wk after intrasplenic injection. Both hepatic as well as pulmonary and lymphatic tumor spread was localized by nuclear imaging with 125I-SF-25. Furthermore, micrometastases were detected by autoradiography 5-10 days later. Monoclonal antibody SF-25 is a potential candidate for tumor localization and the experimental metastatic colon cancer animal model may be useful for treatment evaluation of monoclonal antibody SF-25 either alone or in combination with other monoclonal antibodies when conjugated to radionucleotides and chemotherapeutic agents.

Serial studies of platelet factor 4 and beta thromboglobulin during exercise in patients with coronary artery disease.

In vivo activation of platelets can be accurately measured by radioimmunoassays of platelet factor 4 (PF4) and beta thromboglobulin (beta TG). Studies that attempt to correlate increases in PF4 and beta TG levels with exercise-induced myocardial ischemia have yielded conflicting results. To further examine the natural history of release of PF4 and beta TG we used a method of serial samplings of these proteins during and after exercise in nine normal subjects and 24 patients with coronary artery disease (CAD). Mean values for PF4 and beta TG at rest, during each stage, and immediately after treadmill exercise were the same for normal subjects and for patients with positive and negative responses to exercise-tolerance tests (ETTs). However, nonparametric analysis and regression equations disclosed differences in trends of PF4 level during exercise; PF4 levels increased in normal subjects during exercise, while patients with positive ETTs had no change in PF4 levels and patients with negative ETTs actually showed a decrease in PF4. This investigation confirmed that exercise-induced myocardial ischemia is not associated with platelet aggregation as manifested by the release of the platelet-specific proteins PF4 and beta TG. Statistical analysis suggested that prior reports of elevated levels of PF4 during exercise could have been caused by technical and methodologic difficulties that were associated with the collection and handling of the samples.