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We report a unusual presentation of B-cell lymphoma in the chronically inflamed synovium of a 64-year-old man with an 18-year history of rheumatoid arthritis that was treated with methotrexate.

Iron oxide nanoparticles have been shown to magnetically label cells in order to visualize them in vivo via MR imaging. This technology has yet to be implemented in insulin secreting cells, thus it is not known whether the presence of these nanoparticles in the cytoplasm of the cells affects insulin secretion. This study investigates the effectiveness and consequence of labeling mouse insulinoma betaTC3 and betaTC-tet cells with monocrystalline iron oxide nanoparticles (MION). Our data show that MION can be internalized in both betaTC3 and betaTC-tet cells following a 24h exposure to 0.02mg/ml MION solution. The metabolic and secretory activities of both MION-labeled cell lines were statistically indistinguishable from sham treatment. Furthermore, cell viability and apoptosis remained constant throughout the cell's exposure to MION. Finally, MR images demonstrated significant contrast between labeled and sham-treated cells. Thus, labeling murine insulinoma cell lines with magnetic iron oxide nanoparticles does not hinder their insulin secretion, while it provides MR imaging contrast.

A full account of the development of the first catalytic manifold for the additions of allylboronates to aldehydes is described. The thermal additions (both diastereospecific and enantioselective) of 2-carboxyester 3,3-disubstituted allylboronates 1 to both aromatic and aliphatic aldehydes give biologically and synthetically important exo-methylene butyrolactones 2 containing a beta-quaternary carbon center. Although the thermal reaction requires 14 d at room temperature to reach completion, the presence of certain metal salts allows for a 12-16 h reaction while preserving the diastereospecificity observed in the uncatalyzed process. Preliminary mechanistic studies on the origin of the catalytic effect are described as well as stereoselective transformations of lactones 2 into cyclic and acyclic stereotriads with potential usefulness as synthetic intermediates.

Despite the popularity of boron and silicon allylation reagents in stereocontrolled synthesis, they suffer from a number of inherent limitations that have slowed down their development as synthetic tools for nucleophilic additions to carbonyl compounds and imine derivatives. These limitations are the low reactivity and diastereoselectivity of allyl trialkylsilane reagents, and the lack of catalytic systems for the activation and substoichiometric control of enantioselectivity in the additions of allyl boron reagents. To develop more efficient and general methods for the control of absolute stereochemistry in the resulting homoallylic alcohols, new approaches aimed at solving the problem of activation of allylic boron and silicon reagents are needed. This Minireview describes a number of recent approaches that have been devised to address this problem.

A series of 1,n-dioxa[n](2,7)pyrenophanes (n = 7-12) with increasingly nonplanar pyrene moieties was synthesized by a 9-10 step sequence starting from 5-hydroxyisophthalic acid. The crystal structure of each member of this series was determined crystallographically. Several spectroscopic properties were found to vary with the extent of the nonplanarity of the pyrene unit. The way in which the distortion from planarity of the pyrene system influences its pi-electron delocalization was investigated by using two quantitative descriptors of aromaticity based on geometry (HOMA) and magnetism (magnetic susceptibility and NICS). Both methods suggest that the aromaticity of the pyrene moiety is diminished only slightly upon increasing the bend angle theta from 0 degrees to 109.2 degrees.

This communication successfully challenges the perception that the additions of allylbonates to aldehydes cannot be catalyzed effectively by added Lewis acids. Using a novel class of isomerically pure, tetrasubstituted 2-alkoxycarbonyl allylboronates (1), we describe that some metals (for example, Sc(OTf)(3) and Cu(OTf)(2)) allow these reagents to add onto aldehydes to yield gamma-lactone products 2 in good yields at temperatures almost 100 degrees C lower than the corresponding uncatalyzed reactions. The large rate enhancement over the uncatalyzed reaction provides a highly improved practical approach to access aldol-like adducts with a stereogenic quaternary carbon center. The crucial role of the 2-alkoxycarbonyl group on allylboronates 1 was demonstrated with control experiments using a model allylboronate lacking such an ester group. Moreover, the stereospecificity observed in the uncatalyzed allylborations is preserved. These observations raise intriguing mechanistic issues such as the suggestion that type I allylmetal behavior is maintained in this unprecedented catalytic reaction manifold.

In spite of their inherent isomerization tendency and low reactivity, 1-alkoxycarbonyl vinylcopper(I) intermediates from the conjugate addition of organocuprates onto acetylenic esters were trapped with very high cis-addition selectivity with iodomethylboronic esters in the presence of HMPA. The resulting isomerically pure 3,3-disubstituted allylboronates react with aldehydes in a highly diastereo- and enantioselective manner, providing alpha-exomethylene gamma-lactones with a stereogenic quaternary beta-carbon center.

Background: Patients with peripheral arterial disease (PAD) are at an increased risk of cardiovascular mortality and morbidity and thus are an excellent group in whom to evaluate the feasibility and the effect of an aggressive multifactorial intervention on atherosclerotic vascular disease risk factors. The Arterial Disease Multiple Intervention Trial (ADMIT) was designed to determine the efficacy, safety, and compliance of an multifactorial therapy on selected atherosclerotic disease risk factors in patients with PAD., Methods: By a 2 x 2 x 2 factorial design, eligible participants (N = 468) were randomly assigned to low-dose warfarin, antioxidant vitamins, and niacin or its corresponding placebo, and followed up for 1 year. All participants were encouraged to use aspirin. Pravastatin was added to the drug regimen for those who needed to reduce LDL cholesterol to recommended levels., Results: Niacin increased HDL cholesterol levels by 30%, with the majority of effect achieved at a dosage of 500 mg twice daily. Warfarin had an anticoagulant effect. The antioxidant vitamins resulted in a significant increase in vitamin E, C, and beta-carotene plasma levels. Overall, compliance was high and few adverse effects were reported., Conclusions: ADMIT demonstrates that it is both feasible and safe to modify multiple atherosclerotic disease risk factors effectively with intensive combination therapy in patients with PAD.

Background: Patients with peripheral arterial disease (PAD) have high rates of cardiovascular morbidity and mortality, including that caused by associated coronary heart disease and cerebrovascular disease. Previous studies have shown that coagulation parameters are altered in PAD and that altered coagulation may play a critical role in the susceptibility to cardiovascular complications in PAD. It is therefore important to assess the effect of secondary prevention measures on coagulation in patients with PAD. The Arterial Disease Multiple Intervention Trial (ADMIT), a multicenter, randomized, placebo-controlled trial, was conducted to determine the feasibility of a combined lipid-modifying, antioxidant, and antithrombotic treatment regimen in patients with PAD. The objective of this study was to assess the effect of the ADMIT interventions on coagulation., Methods: ADMIT participants were randomly assigned to low-dose warfarin, niacin, and antioxidant vitamin cocktail or corresponding placebos in a 2 x 2 x 2 factorial design. Specialized coagulation studies were performed in a subset of 80 ADMIT participants at baseline and after 12 months of treatment., Results: Low-dose warfarin (1 to 4 mg/d) resulted in a significant decrease in factor VIIc (P <.001) and in plasma F1.2 (P =.001). Unexpectedly, niacin treatment also resulted in significant decrease in both fibrinogen (48 mg/dL; P <.001) and F1.2 (P =.04). von Willebrand factor increased after antioxidant vitamin treatment (P =.04)., Conclusions: A regimen of low-dose warfarin effectively modifies coagulation in patients with PAD. Niacin also favorably modifies fibrinogen and plasma F1.2. Niacin, in addition to its lipid effects, modifies abnormal coagulation factors that accompany PAD.

Patellar contact forces were measured in 7 fresh-frozen cadaver knees during continuous flexion-extension cycling for the normal knee and after total knee arthroplasty without and with patellar resurfacing using 2 prosthesis systems with different designs for the femoral and patellar components. Analysis of variance with specimen as a repeated measure was used to examine the effect of contact surface. When compared to normal knees, total knee arthroplasty without patellar resurfacing resulted in no change in patellar contact forces. The magnitude of the inferosuperior patellar shear force increased significantly after patellar replacement with an oval, biconcave patellar component and increased further after replacement with an oval, domed patellar component. There were no significant changes in the mediolateral and anteroposterior contact force components after patellar replacement.

Total GLUT4 content in skeletal muscle from individuals with type 2 diabetes is normal; however, recent studies have demonstrated that translocation of GLUT4 to the plasma membrane is decreased in response to insulin stimulation. It is not known whether physical exercise stimulates GLUT4 translocation in skeletal muscle of individuals with type 2 diabetes. Five subjects (two men, three women) with type 2 diabetes and five normal control subjects (5 men), as determined by a standard 75-g oral glucose tolerance test, were recruited to determine whether an acute bout of cycle exercise activates the translocation of GLUT4 to the plasma membrane in skeletal muscle. Each subject had two open biopsies of vastus lateralis muscle; one at rest and one 3-6 weeks later from the opposite leg after 45-60 min of cycle exercise at 60-70% of VO2max. Skeletal muscle plasma membranes were prepared by subcellular fractionation, and GLUT4 content was determined by Western blotting. Plasma membrane GLUT4 increased in each subject in response to exercise. The mean increase in plasma membrane GLUT4 for the subjects with type 2 diabetes was 74 +/-20% above resting values, and for the normal subjects the increase was 71+/-18% above resting values. Although plasma membrane GLUT4 content was approximately 32% lower at rest and after exercise in the muscle of the subjects with type 2 diabetes, the differences were not statistically significant. We conclude that in contrast to the previously reported defect in insulin-stimulated GLUT4 translocation in skeletal muscle of individuals with type 2 diabetes, a single bout of exercise results in the translocation of GLUT4 to the plasma membrane in skeletal muscle of individuals with type 2 diabetes. These data provide the first direct evidence that GLUT4 translocation is an important cellular mechanism through which exercise enhances skeletal muscle glucose uptake in individuals with type 2 diabetes.

Objectives: We sought to determine whether the prehospital electrocardiogram (ECG) improves the diagnosis of an acute coronary syndrome., Background: The ECG is the most widely used screening test for evaluating patients with chest pain., Methods: Prehospital and in-hospital ECGs were obtained in 3,027 consecutive patients with symptoms of suspected acute myocardial infarction, 362 of whom were randomized to prehospital versus hospital thrombolysis and 2,665 of whom did not participate in the randomized trial. Prehospital and hospital records were abstracted for clinical characteristics and diagnostic outcome., Results: ST segment and T and Q wave abnormalities suggestive of myocardial ischemia or infarction were more common on both the prehospital and hospital ECGs of patients with as compared with those without acute coronary syndromes (p < or = 0.00001). Those with prehospital thrombolysis were more likely to show resolution of ST segment elevation by the time of hospital admission (14% vs. 5% in patients treated in the hospital, p = 0.004). In patients not considered for prehospital thrombolysis, both persistent and transient ST segment and T or Q wave abnormalities discriminated those with from those without acute coronary ischemia or infarction. Compared with ST segment elevation on a single ECG, added consideration of dynamic changes in ST segment elevation between serial ECGs improved the sensitivity for an acute coronary syndrome from 34% to 46% and reduced specificity from 96% to 93% (both p < 0.00004). Overall, compared with abnormalities observed on a single ECG, consideration of serial evolution in ST segment, T or Q wave or left bundle branch block (LBBB) abnormalities between the prehospital and initial hospital ECG improved the diagnostic sensitivity for an acute coronary syndrome from 80% to 87%, with a fall in specificity from 60% to 50% (both p < 0.000006)., Conclusions: ECG abnormalities are an early manifestation of acute coronary syndromes and can be identified by the prehospital ECG. Compared with a single ECG, the additional effect of evolving ST segment, T or Q waves or LBBB between serially obtained prehospital and hospital ECGs enhanced the diagnosis of acute coronary syndromes, but with a fall in specificity.

Somatostatin receptors are present in the normal adrenal cortex and medulla. These receptors are also expressed by tumors that cause Cushing's syndrome and by pheochromocytomas. Somatostatin analogues such as octreotide have been developed to target somatostatin receptors for diagnostic and therapeutic purposes. This article reviews the current knowledge of the biology of somatostatin receptors in the normal adrenal gland and in adrenal tumors and defines the current role of the somatostatin receptor in the diagnosis, staging and management of Cushing's syndrome and pheochromocytomas.

Objectives: This study reports the long-term outcome of patients undergoing percutaneous balloon mitral commissurotomy who were enrolled in the National Heart, Lung, and Blood Institute (NHLBI) Balloon Valvuloplasty Registry., Background: The NHLBI established the multicenter Balloon Valvuloplasty Registry in November 1987 to assess both short- and long-term safety and efficiency of percutaneous balloon mitral commissurotomy., Methods: Between November 1987 and October 1989, 736 patients > or = 18 years old underwent percutaneous balloon mitral commissurotomy at 23 registry sites in North America. The maximal follow-up period was 5.2 years., Results: The actuarial survival rate was 93 +/- 1% (mean +/- SD), 90 +/- 1.2%, 87 +/- 1.4% and 84 +/- 1.6% at 1, 2, 3 and 4 years, respectively. Eighty percent of the patients were alive and free of mitral surgery or repeat balloon mitral commissurotomy at 1 year. The event-free survival rate was 80 +/- 1.5% at 1 year, 71 +/- 1.7% at 2 years, 66 +/- 1.8% at 3 years and 60 +/- 2.0% at 4 years. Important univariable predictors of actuarial mortality at 4 years included age > 70 years (51% survival), New York Heart Association functional class IV (41% survival) and baseline echocardiographic score > 12 (24% survival). Multivariable predictors of mortality included functional class IV, higher echocardiographic score and higher postprocedural pulmonary artery systolic and left ventricular end-diastolic pressures (p < 0.01)., Conclusions: Percutaneous balloon mitral commissurotomy has a favorable effect on the hemodynamic variables of mitral stenosis, and long-term follow-up data suggest that it is a viable alternative with respect to surgical commissurotomy in selected patients.

Hyperthyroidism in the older patient often presents with nonspecific symptoms, such as apathy, weight loss, and atrial fibrillation. General screening is not cost-effective, with the exception of two populations: women over age 40 with one or more nonspecific complaints and patients being admitted to a specialized geriatric unit. The sensitive TSH test is an excellent screen; a low TSH should be confirmed by an actual or estimated high free thyroxine test (FT4). The RAIU can help narrow the differential diagnosis. Radioiodine is the preferred treatment for the older patient with Graves' disease, the most common form of thyrotoxicosis. Graves' must be differentiated from thyroiditis and toxic nodular goiters, as treatment regimens differ for each disorder.

Objectives: We sought to determine the cost-effectiveness of the recommendations of cardiologists for the pharmacologic treatment of hypercholesterolemia., Background: Despite the publication of guidelines such as the report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults, little is known about the national prescribing practices of physicians and how they compare with the recommendations of cost-effectiveness analyses., Methods: Under the auspices of the Cardiovascular Norms Committee of the American College of Cardiology, a nationally representative sample of cardiologists was surveyed, and their recommendations for the pharmacologic treatment of hypercholesterolemia were assessed to determine cost-effectiveness., Results: The 346 responding cardiologists were reasonably representative of the membership of the American College of Cardiology. For the 12 hypothetical patients, the cardiologists recommended pharmacologic treatment more commonly in cases in which previously published studies estimated the treatment to be more cost-effective, although there was a tendency to recommend such treatment for primary prevention even when it was estimated to cost well over $100,000/year of life saved., Conclusions: These findings suggest that the cardiologists' pharmacologic recommendations for lowering lipids are correlated with published cost-effectiveness analyses. However, substantial variation in their recommendations remains, with somewhat less aggressive treatment for secondary prevention and more aggressive treatment for primary prevention than would be recommended on the basis of cost-effectiveness analyses.

Objectives: This study compared the rates of coronary artery bypass graft surgery and 15-year survival for men and women after initial medical or surgical management., Background: There has been concern that women with coronary artery disease are managed differently than men and that men and women have a different prognosis. The Coronary Artery Surgery Study (CASS) registry is a large data base of well characterized patients with long-term follow-up., Methods: Patients underwent cardiac catheterization at 1 of 15 hospitals during 1974 to 1979. Bypass surgery rates were based on 12,452 men and 2,366 women. Survival results were based on 6,018 men and 1,095 women with operable coronary artery disease and initial medical management and 6,922 men and 1,291 women initially managed surgically., Results: At 15 years, bypass surgery rates were 75% for men and 72% for women (p = 0.91). The rates remained similar after adjustment for clinical and angiographic variables. The 15-year survival rate was 50% for men and 49% for women with initial medical treatment (p = 0.53) and 52% for men and 48% for women (p = 0.004) with initial surgical treatment, a difference similar to that for operative mortality (men 2.5%, women 5.3%, p < 0.0001). Survival was improved by bypass surgery in most subgroups, with largest relative risks for high risk patients. Relative risks were similar for men and women., Conclusions: The rate of bypass surgery did not differ between men and women. There were few differences in the survival of men and women. In general, both men and women with initial surgical treatment survived longer, although benefits were clinically and statistically significant only in those at high risk. The benefit was similar in both men and women.

There is growing interest in the use of angioplasty as the primary method to achieve coronary artery reperfusion in patients with acute myocardial infarction. The use of thrombolytic therapy has been established as effective in many large clinical trials, while only a few small studies have been completed comparing primary angioplasty with thrombolytic therapy. This paper briefly compares the use of these two treatment modalities and concludes that primary angioplasty is the preferred approach in patients with cardiogenic shock and for those patients with large myocardial infarctions who have contraindications to thrombolytic therapy. Other patients with AMI should receive thrombolytic therapy unless there are contraindications to this treatment.

To determine the clinical value of simple, widely available variables in estimating left ventricular (LV) function, we performed an analysis on 14,507 patients presenting with chest pain who were enrolled in the Coronary Artery Surgery Study registry. Of these patients, 4,034 had a normal electrocardiogram, and of these, 91.8% had an LV ejection fraction (EF) > 0.50, 7.6% had an EF of 0.36 to 0.50, and only 0.6% had an EF < or = 0.35. The presence of T-wave abnormalities (with normal QRS), left bundle branch block, electrocardiographic evidence of LV hypertrophy or myocardial infarction, cardiomegaly on chest roentgenogram, basilar rales, or third heart sound significantly decreased the likelihood of normal LVEF. Based on these clinical variables, a logistic regression model with a sensitivity of 68% and a specificity of 74% for identifying subjects with normal EF was developed. It was concluded that in patients with chest pain, consideration of such readily available clinical data provides useful information and may decrease the need for more expensive imaging methods.

We carried out a systematic overview using individual patient data from the seven randomised trials that have compared a strategy of initial coronary artery bypass graft (CABG) surgery with one of initial medical therapy to assess the effects on mortality in patients with stable coronary heart disease (stable angina not severe enough to necessitate surgery on grounds of symptoms alone, or myocardial infarction). 1324 patients were assigned CABG surgery and 1325 medical management between 1972 and 1984. The proportion of patients in the medical treatment group who had undergone CABG surgery was 25% at 5 years, 33% at 7 years, and 41% at 10 years: 93.7% of patients assigned to the surgery group underwent CABG surgery. The CABG group had significantly lower mortality than the medical treatment group at 5 years (10.2 vs 15.8%; odds ratio 0.61 [95% CI 0.48-0.77], p = 0.0001), 7 years (15.8 vs 21.7%; 0.68 [0.56-0.83], p < 0.001), and 10 years (26.4 vs 30.5%; 0.83 [0.70-0.98]; p = 0.03). The risk reduction was greater in patients with left main artery disease than in those with disease in three vessels or one or two vessels (odds ratios at 5 years 0.32, 0.58, and 0.77, respectively). Although relative risk reductions in subgroups defined by other baseline characteristics were similar, the absolute benefits of CABG surgery were most pronounced in patients in the highest risk categories. This effect was most evident when several prognostically important clinical and angiographic risk factors were integrated to stratify patients by risk levels and the extension of survival at 10 years was examined (change in survival -1.1 [SE 3.1] months in low-risk group, 5.0 [4.2] months in moderate-risk group, and 8.8 [5.4] months in high-risk group; p for trend < 0.003). A strategy of initial CABG surgery is associated with lower mortality than one of medical management with delayed surgery if necessary, especially in high-risk and medium-risk patients with stable coronary heart disease. In low-risk patients, the limited data show a non-significant trend towards greater mortality with CABG.

Background: To identify predictors of long-term outcome after balloon aortic valvuloplasty, we analyzed data on 674 adults (mean age, 78 +/- 9 years; 56% were women) undergoing this procedure at 24 clinical centers who had a mean initial increase in aortic valve area of 0.3 cm2., Methods and Results: Baseline data included clinical, echocardiographic, and catheterization variables. Follow-up data included mortality, cause of death, rehospitalization, 6-month echocardiography, and functional status. Kaplan-Meier curves and log-rank tests were used to evaluate survival in subgroups. Multivariate Cox regression models were used to identify independent predictors of survival. Overall survival was 55% at 1 year, 35% at 2 years, and 23% at 3 years, with the majority of deaths (70%) classified as cardiac by an independent review committee. Rehospitalization was common (64%), although 61% of survivors at 2 years reported improved symptoms. Echocardiography at 6 months (n = 115) showed restenosis from the postprocedural valve area of 0.78 +/- 0.31 cm2 to 0.65 +/- 0.25 cm2 (P < .0001). With stepwise multivariate analysis, sequentially adding clinical, echocardiographic, and catheterization variables, the overall model identified independent predictors of survival as baseline functional status, baseline cardiac output, renal function, cachexia, female gender, left ventricular systolic function, and mitral regurgitation. Baseline and postprocedural variables were examined to identify which subgroup of patients has the best outcome after aortic valvuloplasty. A "lower-risk" subgroup (28% of the study population), defined by normal left ventricular systolic function and mild clinical functional limitation, had a 3-year survival of 36% compared with 17% in the remainder of the study group., Conclusions: Long-term survival after balloon aortic valvuloplasty is poor with 1- and 3-year survival rates of 55% and 23%, respectively. Although survivors report fewer symptoms, early restenosis and recurrent hospitalization are common.

During the crucial stages of tumor cell invasion and metastasis, neoplastic cells must traverse extracellular matrices for their migration to distant sites. Because basement membranes (BM) serve as a critical barrier to such passages, most previous in vitro assay models have utilized either an intact BM or a reconstituted rodent or avian BM-matrix to study this process. We have created a gel-like extracellular matrix derived from human amnions which contained type IV collagen, laminin, entactin, tenascin and heparan sulfate proteoglycan. This matrix, which we called Amgel, was used to study selected steps of invasion including cell attachment to matrix, degradation of it by proteolytic enzymes and movement of human tumor cells through matrix defects. An efficient tumor invasion assay system was developed utilizing filter-supported uniform coatings of this matrix in chambers. Human tumor cells (HT-1080 fibrosarcoma and RL-95 adenocarcinoma), when seeded onto Amgel-coated membranes, attached to matrix within 2 h and initiated a time-dependent migration and invasion process, as verified by biochemical analysis and both light and electron microscopy. In an optimized invasion assay 12-15% of tumor cells completely traversed the matrix during a 72-h period with > 90% viability. In contrast to these highly-invasive cells, normal human foreskin fibroblasts and normal human endometrial stromal cells exhibited minimal migration/matrix penetration during the same time period. When the Amgel-selected tumor cells (i.e. those penetrating the barrier) were isolated, subcultured, and re-exposed to Amgel, they had heightened invasiveness (2-3-fold) as compared to the parental cells. Thus, this improved 'all human' system for quantitating the invasive ability of tumor cells may provide a valuable tool in dissecting out the mechanistic underpinnings of human metastasis. In addition, this assay has the ability to screen agents which have potential anti-invasive and by extension anti-metastatic, activity or chemotactic properties.

Objectives: The aim of this study was to determine whether streptokinase treatment improves long-term survival in patients with acute myocardial infarction., Background: Thrombolytic treatment for acute myocardial infarction reduces early mortality and improves the 1-year survival rate, but the long-term (3 to 8 years) survival benefits of treatment and the relation between survival and baseline clinical characteristics, infarct size and ventricular function have not been established., Methods: We assessed survival status at a minimum of 3 and a mean of 4.9 +/- 2.3 years in 618 patients randomized between 1981 and 1986 to receive conventional treatment (n = 293) or thrombolysis with streptokinase (n = 325) in the Western Washington Intracoronary (n = 250) and Intravenous (n = 368) Streptokinase in Myocardial Infarction trials. The relation between long-term survival and thrombolytic treatment, admission baseline clinical characteristics and late radionuclide tomographic thallium-201 infarct size and ejection fraction was assessed in a subset of patients., Results: Survival at 6 weeks was 94% in patients who received streptokinase versus 88% in the control group (p = 0.01). However, survival at 3 years was 84% in the streptokinase group and 82% in the control group and for the total period of follow-up, there was no significant survival benefit (p = 0.16). Analysis by infarct location showed a higher survival rate at 3 years for patients treated with anterior infarction (76% vs. 67% for the control group), but no overall survival benefit (p = 0.14). Survival at 3 years for patients with an inferior infarction was 89% in the streptokinase group and 91% in the control group (p = 0.62). By stepwise Cox regression analysis, admission clinical variables associated with decreased long-term survival were anterior infarction, advanced age, history of prior infarction and the presence of pulmonary edema or hypotension. Although streptokinase therapy was associated with improved survival, it was not an independent determinant of survival (p = 0.069). Ejection fraction and thallium-201 infarct size measured approximately 8 weeks after enrollment had a strong association with long-term survival. Univariate analysis in a subgroup of 289 patients with complete data selected infarct size, ejection fraction, age and history of prior infarction as predictors of survival. In the multivariate model, only ejection fraction (p < 0.0001), age (p = 0.008) and prior myocardial infarction (p = 0.02) remained strong predictors., Conclusions: In these early trials of thrombolytic therapy for acute myocardial infarction, streptokinase improved early survival, but there was little long-term survival benefit. This failure to show an improvement in the 3- to 8-year survival rate may also reflect the need to study a larger group of patients or to initiate treatment earlier after symptom onset.

Background: The Coronary Artery Surgery Study (CASS) Registry is used to evaluate the effect of various baseline clinical and angiographic factors on mortality after acute out-of-hospital myocardial infarction (MI) in patients with and without prior coronary bypass surgery., Methods and Results: Among the CASS Registry patients, there were 985 medical and 369 surgical patients who had an MI out of the hospital within 3 years after enrollment. In the medical group, 20% died before hospitalization. Medical patients with baseline three-vessel disease or left ventricular (LV) dysfunction were at high risk of immediate death. For medical patients who were hospitalized with MI, mortality was higher for older patients and those with severe angina as well as for those with extensive disease and LV dysfunction. The total 30-day mortality for medical patients was 36%. In the surgical group, 12% died before hospitalization. Surgical patients with LV dysfunction or prior MI were at highest risk of immediate death. For surgical patients hospitalized with MI, mortality was significantly increased only for patients with baseline LV dysfunction. Mortality was not significantly higher for surgical patients with multivessel disease. The total 30-day mortality for surgical patients was 21%. The prior use of aspirin or beta-blockers was not associated with reduced mortality from subsequent MI for either medical or surgical patients. Although the prevalence of cigarette smoking was high among patients who had an MI, cigarette smoking did not alter the infarct-related mortality rate., Conclusions: The surgical group had lower mortality rates than the medical group both immediately (p = 0.001), after hospitalization (p less than 0.0001), and at 30 days (p less than 0.0001).

The findings in 3,256 consecutive patients hospitalized for acute myocardial infarction were tabulated to assess the history, treatments and outcome in the elderly; 1,848 patients (56%) were greater than 65 years of age, including 28% who were aged greater than or equal to 75 years. The incidence of prior angina, hypertension and heart failure (only 3% of patients less than 55 years of age had a history of heart failure compared with 24% greater than or equal to 75 years old) was found to increase with age. Twenty-nine percent of patients less than 75 years of age were treated with a systemic thrombolytic drug compared with only 5% of patients older than 75 years. Mortality rates increased strikingly with advanced age (less than 2% in patients less than or equal to 55, 4.6% in those 55 to 64, 12.3% in those 65 to 74 and 17.8% in those greater than or equal to 75 years). Both the incidence of complicating illness and a nondiagnostic electrocardiogram (ECG) increased with age. In a multivariate analysis of outcome in older patients (greater than or equal to 65 years), adverse events were related to both prior history of heart failure (odds ratio 3.9) and increasing age (odds ratio 1.4 per each decade of age). Outcome was not improved by treatment with thrombolytic drugs, but these agents were prescribed to only 12% of patients greater than 65 years of age, thereby reducing the power for detecting such an effect.(ABSTRACT TRUNCATED AT 250 WORDS)

The clinical characteristics and long-term survival of 284 patients from the Coronary Artery Surgery Study (CASS) registry data base who had moderate to severe congestive heart failure symptoms and a left ventricular ejection fraction greater than or equal to 0.45 were studied. A control group consisting of registry patients with an ejection fraction greater than or equal to 0.45 who did not have heart failure was used for comparison. Patients who had heart failure were older and more likely to be female and to have a higher incidence of hypertension, diabetes and chronic lung disease than registry patients who did not have heart failure. As a group, patients with heart failure had more severe angina and were more likely to have had a prior myocardial infarction than were registry patients without heart failure. At 6 year follow-up, 82% of patients in the heart failure group survived compared with 91% of patients in the control group (p less than 0.0001). Multivariate analysis using the Cox proportional hazards model identified the following independent predictors of mortality: regional ventricular systolic dysfunction, number of diseased coronary arteries, advanced age, hypertension, lung disease, diabetes, increased left ventricular end-diastolic pressure and heart failure symptoms. Among patients with heart failure, the 6-year survival rate of those who had three-vessel coronary artery disease was 68% compared with 92% for the group without coronary artery disease. However, the 6-year survival rate for patients with heart failure who underwent surgical revascularization of diseased coronary arteries was not significantly improved compared with that of patients treated medically.(ABSTRACT TRUNCATED AT 250 WORDS)

A prehospital computer-interpreted electrocardiogram (ECG) was obtained in 1,189 patients with chest pain of suspected cardiac origin during an ongoing trial of prehospital thrombolytic therapy in acute myocardial infarction. Electrocardiograms were performed by paramedics 1.5 +/- 1.2 h after the onset of symptoms. Of 391 patients with evidence of acute myocardial infarction, 202 (52%) were identified as having ST segment elevation (acute injury) by the computer-interpreted ECG compared with 259 (66%) by an electrocardiographer (p less than 0.001). Of 798 patients with chest pain but no infarction, 785 (98%) were appropriately excluded by computer compared with 757 (95%) by an electrocardiographer (p less than 0.001). The positive predictive value of the computer- and physician-interpreted ECG was, respectively, 94% and 86% and the negative predictive value was 81% and 85%. Prehospital screening of possible candidates for thrombolytic therapy with the aid of a computerized ECG is feasible, highly specific and with further enhancement can speed the care of all patients with acute myocardial infarction.

Since 1988, 641 black and 11,892 white patients with chest pain of presumed cardiac origin have been admitted to coronary care units in 19 hospitals in metropolitan Seattle. Black men and women were younger (58 vs 66, p less than 0.0001), more often admitted to central city hospitals (p less than 0.0001), and developed evidence of acute myocardial infarction (AMI) less often (19 vs 23%, p = 0.01). In the subset of 2,870 AMI patients, blacks (n = 121) were younger (59 vs 67, p less than 0.0001) and had less prior coronary artery bypass graft surgery (2 vs 10%, p = 0.005) and more prior hypertension (67 vs 46%, p less than 0.0001). During hospitalization, whites (n = 2,749) had higher rates of coronary angioplasty (18 vs 10%, p = 0.03) and coronary artery bypass graft surgery (10 vs 4%, p = 0.04), although thrombolytic therapy and cardiac catheterization were used equally in the 2 groups. Hospital mortality was 7.4% for black and 13.1% for white patients (p = 0.07). However, after adjustment for key demographic and clinical variables by logistic regression, this difference was not as apparent (p = 0.38). Questions about the premature onset of coronary artery disease, excess systemic hypertension, and the differential use of interventions in black persons have been raised by other investigators. Despite differences in age, referral patterns and the use of coronary angioplasty and bypass surgery, black and white patients with AMI in metropolitan Seattle had similar outcomes.

This study comprised a registry and an emergency department treatment trial using recombinant tissue plasminogen activator. During 1 year, 1,028 patients with documented acute myocardial infarction (AMI) were evaluated for eligibility for thrombolytic therapy. Of these, 221 patients (22%) were eligible for thrombolytic therapy under currently accepted criteria, 175 (79%) of them were correctly identified by emergency department physicians for thrombolytic therapy, and 160 were enrolled in the trial. Only 3 patients (2%) enrolled by emergency department physicians did not subsequently evolve documented AMI. In all, 807 patients (78%) were ineligible for thrombolytic therapy: 335 (33%) because of greater than or equal to 1 contraindications, 364 (36%) because of nondiagnostic electrocardiograms on presentation, and 105 (10%) because of age greater than 75 years, or greater than 6 hours of chest pain at presentation, or both. Mortality in treated patients at 14 days was 5.6%, and survival at 1 year was 92%. The mean time from hospital arrival to thrombolytic treatment was 55 +/- 27 minutes. Initial management of AMI with recombinant tissue plasminogen activator in the emergency department provided rapid and safe treatment comparable to that reported in trials that started treatment in the coronary care unit. The proportions of eligible patients could be increased from 1 in 5 to 1 in 3, if patients currently excluded only because of age greater than 75 years or because of greater than 6 hours of chest pain were offered treatment.