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Biomedical subjects

W D Weaver

Publications and source records attributed to W D Weaver.

At least 109 records · Page 6Linked to original sources
PubMed1994

New recombinant glycosylated prourokinase for treatment of patients with acute myocardial infarction. Prourokinase Study Group.

OBJECTIVES: Three dosage regimens of a new recombinant glycosylated prourokinase (A-74187) were evaluated by measuring coronary artery patency at 90 min in patients with acute myocardial infarction. BACKGROUND: Prourokinase is a thrombolytic drug with unique pharmacologic properties that may be clinically advantageous. METHODS: Aspirin (325 mg), intravenous heparin and prourokinase (60- or 80-mg monotherapy or 60 mg "primed" with a preceding bolus dose of 250,000 IU of recombinant urokinase) were administered to 128 patients. Coronary angiography was performed at 60 min (wherever possible), 90 min (primary end point) and 24 h to determine arterial patency and reocclusion rates. Plasma was collected serially to measure fibrinogen, plasminogen, thrombin antithrombin III and fibrinopeptide A. Clinical events until hospital discharge were recorded. RESULTS: The coronary artery patency rate at 90 min was similar for all three regimens, averaging 73% (95% confidence interval [CI] 64% to 80%); Thrombolysis in Myocardial Infarction (TIMI) grade 3 flow rates averaged 52% (95% CI 42% to 61%). Arterial patency at 60 min was 62% (95% CI 50% to 73%), and reocclusion occurred in 1.4% (95% CI 0.1% to 4.1%). Prourokinase demonstrated relative fibrin specificity at all doses studied. Fibrinopeptide A and thrombin antithrombin III levels were elevated at baseline and declined rapidly during the 1st 12 h. There was no difference in the baseline values of these thrombin markers between patients with patent versus closed arteries at 90 min. There was one death; no strokes occurred. CONCLUSIONS: A-74187 prourokinase is a rapid-acting, effective fibrin-specific thrombolytic agent. Reocclusion was unusual, possibly because of aggressive anticoagulation with intravenous heparin or unique features of the drug. Full definition of the clinical effectiveness of this drug merits examination in future randomized trials evaluating clinical and angiographic effectiveness.

Aspirin↗
PubMed1994

Prehospital thrombolysis in myocardial infarction.

Studies comparing paramedic-initiated and hospital-initiated therapy show that the critical issue is not where or by whom thrombolysis is started but when it is started. Two of the greatest time-savers--and hence modifiers of infarct size and mortality--have been the introduction of the computer-interpreted ECG and simply alerting the hospital that a patient with a diagnosed acute MI will be arriving shortly.

Electrocardiography↗
PubMed1994

Treatment of myocardial infarction in the United States (1990 to 1993). Observations from the National Registry of Myocardial Infarction.

BACKGROUND: Multiple clinical trials have provided guidelines for the treatment of myocardial infarction, but there is little documentation as to how consistently their recommendations are being implemented in clinical practice. METHODS AND RESULTS: Demographic, procedural, and outcome data from patients with acute myocardial infarction were collected at 1073 US hospitals collaborating in the National Registry of Myocardial Infarction during 1990 through 1993. Registry hospitals composed 14.4% of all US hospitals and were more likely to have a coronary care unit and invasive cardiac facilities than nonregistry US hospitals. Among 240,989 patients with myocardial infarction enrolled, 84,477 (35.1%) received thrombolytic therapy. Thrombolytic recipients were younger, more likely to be male, presented sooner after onset of symptoms, and were more likely to have localizing ECG changes. Among the 60,430 patients treated with recombinant tissue-type plasminogen activator (rTPA), 23.2% received it in the coronary care unit rather than in the emergency department. Elapsed time from hospital presentation to starting rTPA averaged 99 minutes (median, 57 minutes). Among patients receiving thrombolytic therapy, concomitant pharmacotherapy included intravenous heparin (96.9%), aspirin (84.0%), intravenous nitroglycerin (76.0%), oral beta-blockers (36.3%), calcium channel blockers (29.5%), and intravenous beta-blockers (17.4%). Invasive procedures in thrombolytic recipients included coronary arteriography (70.7%), angioplasty (30.3%), and bypass surgery (13.3%). Trend analyses from 1990 to 1993 suggest that the time from hospital evaluation to initiating thrombolytic therapy is shortening, usage of aspirin and beta-blockers is increasing, and usage of calcium channel blockers is decreasing. CONCLUSIONS: This large registry experience suggests that management of myocardial infarction in the United States does not yet conform to many of the recent clinical trial recommendations. Thrombolytic therapy is underused, particularly in the elderly and late presenters. Although emerging trends toward more appropriate treatment are evident, hospital delay time in initiating thrombolytic therapy remains long, aspirin and beta-blockers appear to be underused, and calcium channel blockers and invasive procedures appear to be overused.

Drug Therapy, Combination↗
PubMed1993

Hospital mortality in acute myocardial infarction in the era of reperfusion therapy (the Myocardial Infarction Triage and Intervention Project).

This study was conducted in 19 hospitals in the metropolitan Seattle area and included 6,270 unselected patients who had acute myocardial infarction (AMI) between January 1988 and April 1991. Hospital mortality was determined and related to patient demographic and clinical characteristics, the use of reperfusion therapies, and to complications after AMI. Thrombolytic therapy or direct coronary angioplasty < 6 hours from symptom onset was used to treat 1,185 (19%) and 524 (9%) patients, respectively. There were 629 (10%) hospital deaths; most occurred during the first 3 days of hospitalization. Factors affecting mortality after admission included: recurrent chest pain, recurrent AMI, development of heart failure, and the occurrence of stroke. After adjustment for age, treatment with thrombolytic therapy or direct angioplasty had no independent effect on reducing the overall mortality rate. Hospital mortality rates for AMI have improved considerably since 1970, although recurrent myocardial ischemic events continue to have an adverse effect on outcome. The current use of reperfusion treatments has had minimal causal impact on overall mortality rates, principally because less than one third of patients, who are relatively "low risk," are eligible and receive these treatments.

Adult↗
PubMed1993

Prehospital-initiated vs hospital-initiated thrombolytic therapy. The Myocardial Infarction Triage and Intervention Trial.

OBJECTIVE: To determine the effect of prehospital-initiated vs hospital-initiated treatment of myocardial infarction on clinical outcome. DESIGN: Randomized, controlled clinical trial. SETTING: Multicenter study involving 19 hospitals and all paramedic systems in the Seattle, Wash, metropolitan area. PATIENTS: A total of 360 patients with symptoms for 6 hours or less, no risk factors for serious bleeding, and ST-segment elevation were selected by paramedics and a remote physician for inclusion into the trial. They represented 4% of patients with chest pain who were screened and 21% of those with acute infarction. INTERVENTIONS: Patients were allocated to have aspirin and alteplase treatment initiated before or after hospital arrival. Intravenous sodium heparin was administered to both groups in the hospital. MAIN OUTCOME MEASURE: The primary endpoint was a ranked composite score (combining death, stroke, serious bleeding, and infarct size). The relation between time to treatment and outcome (composite score, infarct size, ejection fraction, and mortality) was also assessed. RESULTS: Initiating treatment before hospital arrival decreased the interval from symptom onset to treatment from 110 to 77 minutes (P < .001). Although more patients whose therapy was initiated before hospital arrival had resolution of pain by admission (23% vs 7%; P < .001), there were no significant differences in the composite score (P = .64), mortality (5.7% vs 8.1%), ejection fraction (53% vs 54%), or infarct size (6.1% vs 6.5%). A secondary analysis of time to treatment and outcome showed that treatment initiated within 70 minutes of symptom onset was associated with better outcome (composite score, P = .009; mortality, 1.2% vs 8.7%, P = .04; infarct size, 4.9% vs 11.2%, P < .001; and ejection fraction, 53% vs 49%, P = .03) than later treatment. Identification of patients eligible for thrombolysis by paramedics reduced the hospital treatment time from 60 minutes (for patients not in the study) to 20 minutes (for study patients allocated to begin treatment in the hospital). CONCLUSION: There was no improvement in outcome associated with initiating treatment before hospital arrival; however, treatment within 70 minutes of symptom onset--whether in the hospital or in the field--minimized the infarct process and its complications.

Aged↗
PubMed1993

The association between on-site cardiac catheterization facilities and the use of coronary angiography after acute myocardial infarction. Myocardial Infarction Triage and Intervention Project Investigators.

BACKGROUND: During the past decade the use of coronary angiography after acute myocardial infarction has substantially increased. Among the possible contributing factors, the increasing availability of cardiac catheterization facilities was the focus of our investigation. METHODS: We investigated whether the availability of cardiac catheterization facilities at an admitting hospital was associated with the likelihood that a patient would undergo coronary angiography. After adjusting for age, sex, cardiac history, and cardiac complications during hospitalization, we evaluated this association in 5867 consecutive patients with acute myocardial infarction admitted to 19 Seattle-area hospitals. We also assessed the association between the presence of on-site cardiac catheterization facilities and in-hospital mortality. RESULTS: Patients admitted to hospitals with on-site cardiac catheterization facilities were far more likely to undergo coronary angiography (odds ratio, 3.21; 95 percent confidence interval, 2.81 to 3.67) than patients admitted to hospitals where transfer to another institution would be required to perform cardiac catheterization. Admission to a hospital with on-site facilities was more strongly associated with the use of coronary angiography than any characteristic of the patient. Although our study had limited power to detect differences in mortality, the availability of coronary angiography had no discernible association with in-hospital mortality rates (odds ratio for mortality among patients admitted to hospitals with on-site facilities vs. patients admitted to hospitals without such facilities, 0.88; 95 percent confidence interval, 0.71 to 1.09). CONCLUSIONS: In this community-wide study, the availability of on-site cardiac catheterization facilities was associated with a higher likelihood that a patient would undergo coronary angiography. However, admission to hospitals with these facilities did not appear to be associated with lower short-term mortality.

Aged↗
PubMed1993

Thrombolytic therapy.

All patients with symptoms and ECG findings suggestive of acute myocardial infarction (AMI) should be considered for treatment with thrombolytic agents. The decision to use thrombolytic therapy is a clinical judgment based upon a weighing of the potential benefits versus the possible risks. The physician must take into account relative contraindications, age of the patient, area of jeopardized myocardium, and duration of symptoms. Health professionals involved in the care of AMI patients should develop written plans and protocols addressing the following matters: identification of patients with chest pain in the prehospital setting (this applies to hospitals that receive patients from emergency medical services systems), triage of patients in the emergency department, obtaining the 12-lead electrocardiogram, determination of contraindications, authority for ordering thrombolytic therapy, and consultation for atypical cases. There also should be agreed standards for the time interval from arrival in the ED to administration of the thrombolytic agent, as well as a commitment to the prospective monitoring of procedures and times to assure continuous improvement. A time interval for treatment (arrival in ED to administration of drug) of 30 to 60 minutes should be achievable for patients who present with typical symptoms and ECG findings.

Acute Disease↗
PubMed1993

Influence of external defibrillator electrode polarity on cardiac resuscitation.

Eight hundred forty-seven consecutive patients discovered in cardiac arrest by first responding firefighters received initial defibrillation attempts using automatic external defibrillators. The effect of electrode polarity on defibrillation and resuscitation was determined in the subset of 289 (34%) with ventricular fibrillation in a prospective, randomized trial. The ECG was recorded in 205 consecutive patients whose initial rhythm was ventricular fibrillation. Eighty-seven of 114 patients (76%) in whom the apex chest electrode was positive were defibrillated with the first 200-joule shock, compared to 70 of 91 patients (77%) in whom the apex electrode was negative. There was no difference in the type of rhythm established, e.g., organized versus brady-asystole following defibrillation with either electrode polarity. Resuscitation was possible in 56% of patients in whom the apex electrode was positive and 60% of those in whom the apex electrode was of negative polarity. Hospital survival rates (26% vs 27%) were also similar for both treatment groups. Unlike results during experimental external defibrillation of animals or those obtained using implantable defibrillators, this randomized trial of external defibrillation conducted during attempted out-of-hospital resuscitation showed no difference in outcomes related to electrode polarity.

Aged↗
PubMed1993

Use of direct angioplasty for treatment of patients with acute myocardial infarction in hospitals with and without on-site cardiac surgery. The Myocardial Infarction, Triage, and Intervention Project Investigators.

BACKGROUND: In the Myocardial Infarction, Triage, and Intervention (MITI) registry of acute myocardial infarction, 441 (12%) of 3750 patients had direct angioplasty as initial treatment. Approximately half (233) were performed in hospitals with no on-site surgery. METHODS AND RESULTS: Procedure success rates, use of emergent surgery, and factors influencing outcome were compared in both angioplasty groups as well as with 653 patients treated with thrombolytic therapy in the same hospitals. There was no difference in baseline characteristics between patient groups treated by angioplasty in the two types of hospitals. Patency was established in 88% of patients. Only 1.4% underwent emergent surgery. Overall, survival was 93% but was significantly worse after a failed procedure in all ECG and hemodynamic subsets as well as in those with prior bypass surgery. In a multivariate analysis, age, initial heart rate, blood pressure, and prior bypass surgery but not type of hospital were predictive of survival. Survival rates were similar, but there tended to be fewer strokes (0.6% versus 2.1%, P = .12), shorter hospital stays (7.0 versus 8.1 days, P < .001), and less recurrent ischemia (20% versus 30%, P = .009) in patients treated by angioplasty compared with thrombolysis. Readmission and reinfarction rates were similar for both treatments. CONCLUSIONS: Observations from this community registry suggest that mortality after direct angioplasty is low and the use of emergent surgery is infrequent. Outcome in this registry study was dependent on initial hemodynamic findings and infarct location but not on the presence of on-site surgery. Compared with thrombolytic therapy, the incidence of complications was the same or lower, but this needs confirmation in randomized trials.

Aged↗
PubMed1993

Myocardial infarction, thrombolytic therapy, and stroke. A community-based study. The MITI Project Group.

BACKGROUND: Thrombolytic therapy used in patients with acute myocardial infarction may increase the risk of stroke. Scant information is available from community-based studies. SUMMARY OF REPORT: Among 5,635 consecutive patients admitted with acute myocardial infarction to hospitals in Seattle and surrounding suburban King County, Washington, 116 (2.1%) experienced strokes during hospitalization. Of these strokes, 82 (71%) were ischemic and 34 (29%) were hemorrhagic, defined by a patient's having had a computed tomographic scan of the head that showed blood. Thrombolytic therapy was given to 1,413 of these patients (25%) and was associated with increased risk of hemorrhagic stroke but reduced risk of ischemic stroke. The relative risk of stroke with thrombolytic therapy was estimate using multiple logistic regression to adjust for potential confounding factors. The adjusted relative risk for hemorrhagic stroke was 3.6 (95% confidence interval [CI], 1.7-8.0); for ischemic stroke, 0.4 (95% CI, 0.2-0.9); and for overall stroke, 1.0 (95% CI, 0.6-1.7). The adjusted risk for death from any cause following stroke was 3.0 (95% CI, 1.4-6.4). CONCLUSIONS: Although thrombolytic therapy had little effect on the overall occurrence of stroke, thrombolytic therapy increased the risk of stroke death because more patients with hemorrhagic than ischemic strokes died during their hospitalization. The rates of hemorrhagic stroke with thrombolytic therapy reported in the present study are higher than those reported in clinical trials in which treatment is given to select patients under strict protocols.

Aged↗
PubMed1993

Early feed restriction of broilers: effects on abdominal fat pad, liver, and gizzard weights, fat deposition, and carcass composition.

A total of five experiments were conducted to investigate the effects of early feed restriction on organ weights, fat deposition, and carcass composition in broilers. In Experiments 1 and 2, broiler chicks were reared in litter pens for 49 days, whereas Experiments 3, 4, and 5 were conducted in battery cages for 28 days. Feed restriction in all experiments was accomplished by providing male broiler chicks 40 kcal per bird per day for 7 (Experiments 1 and 2) or 6 (Experiments 3, 4, and 5) days, starting at 4 days of age. Feed restriction of broiler pullets in Experiment 1 was imposed from 4 to 9 days of age. Furthermore, the starter and grower diets in Experiment 2 contained either 1 or 4% added fat and the starter diets in Experiments 3, 4, and 5 contained either 21 or 26% protein. No significant differences were observed for abdominal fat pad and gizzard weights, liver and carcass fat, or carcass protein between early restricted birds and ad libitum controls at 49 days of age in Experiments 1 and 2. Furthermore, with the exception of Experiment 4, no differences in abdominal fat pad weights were observed among the different feeding regimens. Significant increases in abdominal fat pad weights, percentage liver, and percentage carcass fat were noted for females at 49 days of age when compared with male broilers. Carcass fat was significantly higher and carcass protein was significantly lower in broilers fed commercial versus reduced fat diets. Broilers fed a 21% protein diet had significantly heavier abdominal fat pad weights at 28 days of age than birds fed a 26% protein diet.

Adipose Tissue↗
PubMed1993

Characterization of lipogenic and lipolytic activity, muscle tissue composition, and DNA and RNA levels of broilers eating ad libitum or severely restricted at an early age.

Four experiments were conducted to characterize the rates of lipogenic and lipolytic activities and the composition and DNA and RNA concentrations in muscle tissue of broilers that were feed restricted at an early age. In all experiments, feed restriction (40 kcal/day per bird) was initiated at 4 days of age with ad libitum consumption of feed resuming at either 11 (Experiments 1 and 2) or 10 (Experiments 3 and 4) days of age. Female chicks in Experiment 1 were feed restricted at the same level from 4 to 9 days of age. Birds consuming feed ad libitum served as controls in all experiments. Broilers restricted for 7 days had significantly lower plasma very low density plus low density lipoproteins (VLDL+LDL) than the ad libitum birds at 49 days of age in Experiments 1 and 2. However, the reverse was observed at 28 days of age, as plasma triglycerides and lipoproteins and lipogenesis were greater in restricted chicks when compared with controls. No significant differences were observed in plasma triglycerides at 49 days of age or lipolysis, DNA and RNA concentrations, muscle protein, and muscle fat at 28 days of age between restricted and ad libitum broilers. Results from these studies indicate that early feed restriction may have induced a metabolic shift in restricted broilers that increased lipogenesis at 28 days of age, followed by a partitioning of excess nutrients to support anabolic activity at market age.

Adipose Tissue↗
PubMed1992

Influence of coronary bypass surgery on subsequent outcome of patients resuscitated from out of hospital cardiac arrest.

The effect of coronary bypass surgery on recurrent cardiac arrest was estimated in 265 patients resuscitated from out of hospital cardiac arrest between 1970 and 1988. From this cohort, 85 patients (32%) underwent coronary bypass surgery after recovery from cardiac arrest and 180 patients (68%) were treated medically. A multivariate Cox analysis was used to estimate the effect of coronary bypass surgery on subsequent survival after adjusting for effects of age, prior cardiac history, ejection fraction, year of the event, history of angina, antiarrhythmic drug use and whether the arrest was related to acute myocardial infarction. The use of coronary bypass surgery had a significant effect in reducing the incidence of subsequent cardiac arrest during follow-up study (risk ratio [RR] 0.48, 95% confidence interval [CI] 0.24 to 0.97, p less than 0.04). There was also a trend consistent with a reduction in total cardiac mortality (RR 0.65, 95% CI 0.39 to 1.10, p = 0.10). These findings suggest that coronary bypass surgery may reduce the incidence of sudden death in suitable patients resuscitated from an episode of ventricular fibrillation.

Cohort Studies↗