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Biomedical subjects

A Langer

Publications and source records attributed to A Langer.

At least 55 records · Page 3Linked to original sources
PubMed1997

Time to treatment with thrombolytic therapy: determinants and effect on short-term nonfatal outcomes of acute myocardial infarction. Canadian GUSTO Investigators. Global Utilization of Streptokinase and + PA for Occluded Coronary Arteries.

OBJECTIVES: To characterize the extent of delay in administration of thrombolytic therapy to patients with acute myocardial infarction (AMI) in Canada, to examine patient-specific predictors of such delay and to measure the effect of delay on short-term nonfatal cardiac outcomes. DESIGN: Secondary cohort analysis of data from the first international Global Utilization of Streptokinase and tPA for Occluded Coronary Arteries (GUSTO-I) trial. SETTING: Sixty-three acute care hospitals across Canada. SUBJECTS: All 2898 Canadian patients with an AMI enrolled in GUSTO-I. MAIN OUTCOMES: Time before arrival at a hospital ("symptom-to-door" time) and time from arrival to administration of therapy ("door-to-needle" time) for patients who had an AMI outside of a hospital, in clinically relevant categories; proportions of patients with nonfatal, serious cardiac events, including shock, sustained ventricular tachycardia, ventricular fibrillation and asystole. RESULTS: Of the total number of patients enrolled, records were complete for 2708; 2542 of these patients (93.9%) had an AMI outside of a hospital. These 2542 patients presented a median 81 (interquartile range 50 to 130) minutes after the onset of symptoms, and the median time to treatment in hospital was 85 (interquartile range 61 to 115) minutes. Whereas a greater proportion of Canadian patients than of patients enrolled in GUSTO-I in other countries reached hospital within 2 hours of symptom onset (71.5% v. 61.2%, p < 0.001), a greater proportion of Canadian patients experienced in-hospital treatment delays of more than 1 hour (75.3% v. 57.1%, p < 0.001). In an analysis of all 2708 patients with complete records, both the unadjusted and adjusted odds of nonfatal cardiac events for those treated 4 to 6 hours after symptom onset were significantly higher than for those treated within 2 hours (odds ratio 1.60, 95% confidence interval 1.09 to 2.37). CONCLUSION: After arrival at a hospital, Canadian patients enrolled in GUSTO-I received thrombolytic therapy more slowly than trial enrollees in other countries. Such delays are already known to decrease the rate of short-term survival after AMI. The findings further show that long time to treatment also increases the odds of nonfatal, serious cardiac events. Hospitals and physicians caring for patients with AMI should routinely assess whether and how they can improve door-to-needle times.

Adult↗
PubMed1997

The Essence Trial: Efficacy and Safety of Subcutaneous Enoxaparin in Unstable Angina and Non-Q-Wave MI: A Double-Blind, Randomized, Parallel-Group, Multicenter Study Comparing Enoxaparin and Intravenous Unfractionated Heparin: Methods and Design.

Antithrombotic therapy reduces the risk of recurrent ischemic events in patients with unstable angina. The primary aim of the ESSENCE trial is to evaluate the efficacy of enoxaparin (low molecular weight heparin) versus unfractionated heparin, plus aspirin, in patients with rest angina or non-Q-wave infarction. This is a randomized, double-blind, placebo-controlled study of 3180 patients comparing enoxaparin, 1 mg/kg sc bid, with unfractionated heparin via continuous iv infusion to maintain the aPTT at 2 x control. Patients within 24 hours of the onset of acute myocardial ischemia without ST elevation are eligible, and trial therapy is administered for a minimum of 48 hours to a maximum of 8 days. Primary endpoints analyzed are death, myocardial infarction (MI), or recurrent angina at 14 days. Currently 3019 patients have been randomized in 10 countries. The mean age is 64 years, 33% are female, and 46% have had a prior MI. The overall event rates at 14 days are 1.7% mortality, 5.9% subsequent MI, and 17% recurrent angina. The composite triple endpoint rate is 23.6%. Recruitment should be complete by June 1996. The methods and design of the study are presented in this article.

Journal Article↗
PubMed1997

The role of diltiazem in treating hypertension and coronary artery disease: new approaches to preventing first events.

OBJECTIVE: To review the role of diltiazem in treating and preventing a group of cardiovascular diseases, including painful and silent cardiac ischemia, stroke, nonfatal myocardial infarction and sudden cardiac death, by modulating certain physiological causes that they appear to share. DATA SOURCES: A MEDLINE search was conducted for all clinical articles on the use of diltiazem for hypertension and coronary artery disease. When clinical data were not available, basic research findings were reviewed. DATA EXTRACTION AND SYNTHESIS: Because many cardiovascular events show a marked daily periodicity--which appears to coincide with circadian peaks in the ability of platelets to aggregate, sympathetic activity, coronary tone, blood pressure, heart rate and hematocrit, and a trough in fibrinolytic activity--the impact of diltizazem on these physiological changes was assessed. CONCLUSIONS: Diltiazem influences many of these events by increasing myocardial bloodflow, and reducing myocardial oxygen demand and cardiac workload. However, it differs from other calcium antagonists in its mild negative inotropic and moderate negative dromotropic effects, without apparent stimulation of cardiac performance or contractility. In addition, it inhibits platelet aggregation, decreases catecholamine release, diminishes coronary tone and blocks the vasoconstrictive actions of endothelin-1. This appears to translate into a beneficial effect on ischemia, thrombolysis, arrhythmias, infarct parameters, atherosclerosis and hypertension. Diltiazem has a relatively favourable safety and tolerability profile, and is available in a once-daily dosage form. The most common adverse effects are related to vasodilation (eg, edema and headache), and the most frequent serious adverse event is atrioventricular block, which occurs rarely. In summary, diltiazem appears to be well suited to preventing the first occurrence of cardiovascular events and may even have a role in preventing certain types of secondary events. The data accumulated so far indicate the need for a large scale random clinical trial addressing these outcomes.

Arrhythmias, Cardiac↗
PubMed1996

Heart rate variability assessment early after acute myocardial infarction. Pathophysiological and prognostic correlates. GUSTO ECG Substudy Investigators. Global Utilization of Streptokinase and TPA for Occluded Arteries.

BACKGROUND: Diminished heart rate variability is associated with less favorable prognosis after myocardial infarction. However, the prognostic value of early (first 48 hours) measurement and the influence of thrombolytic strategies, myocardial infarction location, left ventricular function, ST-segment shift, and infarct-related artery patency on heart rate variability have not been examined comprehensively. METHODS AND RESULTS: Heart rate variability and ST-segment analysis of 48-hour Holter tapes were performed with the use of a commercial system in 204 patients who were part of an ST-monitoring substudy of the Global Utilization of Streptokinase and TPA for Occluded Arteries (GUSTO-I) trial. Both time-domain measures (SD of the average normal RR interval for all 5-minute segments of a 24-hour ECG recording [SDANN] and percent difference between adjacent normal RR intervals > 50 ms computed over the entire 24-hour ECG recording [pNN50]) and frequency-domain measures (low frequency [LF], high frequency [HF], and LF/HF ratio) were assessed on days 1 and 2 after acute myocardial infarction. Coronary angiography performed within the first 24 hours was also available in 75% of the patients. All heart rate variability measures decreased between day 1 and day 2 (P = .001) except the LF/HF ratio. There was no difference in heart rate variability among groups assigned to one of four different thrombolytic treatment strategies (streptokinase/subcutaneous heparin, streptokinase/intravenous heparin, accelerated tissue plasminogen activator, and combination streptokinase/tissue plasminogen activator). Heart rate variability measures were lower in anterior versus nonanterior infarcts (SDANN, 53 +/- 21 versus 63 +/- 24 ms; P < .005) and increased with TIMI grade 3 flow (LF, 5.3 +/- 1.0 versus 4.8 +/- 1.2 ms2; P < .01) and better ejection fraction (r = .2, P < .03). An inverse correlation between the duration of ST shift and frequency domain measures was observed (LF, r = -.2, P < .009; HF, r = -2, P < .03). Lower LF/HF ratio by 24 hours after myocardial infarction was seen in those who ultimately died at 30 days (1.0 +/- 0.2 versus 1.3 +/- 0.2, P < .001) or at 1 year (1.17 +/- 0.14 versus 1.26 +/- 0.19, P = .05). CONCLUSIONS: Changes in heart rate variability occurred early after thrombolysis and may be of prognostic value. Heart rate variability measures were improved in patients with better ejection fraction and greater angiographic patency. This suggests a possible mechanism for the enhanced survival observed with TIMI grade 3 flow in the GUSTO angiographic substudy. These data indicate that early heart rate variability assessment after myocardial infarction may be useful in noninvasive risk stratification.

Bradycardia↗
PubMed1996

Variations in measured vessel diameters using coronary measurement system.

The Coronary Measurement System (CMS, MEDIS, Leiden, Netherlands) is a film-based QCA system that allows the user to vary the intensity of the light source which illuminates the film, thereby changing the brightness of the image viewed by the digitizing video camera. We found that significant variations in calibration factor (mm/pixel) and measured diameter can occur as a result of variations in either of these intensities. We calculated the variability of the measured diameters for a range of light intensities used for vessel measurement and for calibration. The root mean square deviations in estimated vessel diameter for simulated vessels having actual diameters of 2.03, 2.56, 3.03, and 3.55 mm were 0.13, 0.13, 0.13, and 0.11 mm, respectively, while the ranges (maximum-minimum estimates) were 0.47, 0.45, 0.47, and 0.36 mm, respectively. These results show that while mean errors due to changes in brightness are small, there is the potential for larger errors for certain combinations of light intensities.

Coronary Angiography↗
PubMed1996

Ethnography of fertility and menstruation in rural Mexico.

In rural populations in Mexico, the system of ideas in relation to the reproductive cycle is built on a mestizo base, with pre-Colombian and Western elements. The objective of the study was the analysis of concepts and resources related to human reproduction in Morelos, in order to design a primary reproductive health care program. The use of ethnographic methods helped identify bio-cultural constructs on which the communities base their reproductive patterns. Our main research results reveal that these populations attribute great value to the extension of the family through descendants. Women's sexuality is directly linked to reproduction and blood is the supremely feminine substance. Great importance is consistently attributed to menstruation about which well-defined concepts exist in the community, where as pre-menarche changes are perceived as a state of bio-psychosocial maturity. Menarche beyond 14 years of age is considered abnormal and is attributed to an 'excess of cold' in the body, therapy is usually administered by traditional birth attendants. In the mythical explanations given for bleeding, the moon plays a fundamental role, as the first rupture of the hymen is attributed to it. A general lack of knowledge about ovulation and its relation to reproduction was observed, resulting in incorrect contraceptive practices.

Adolescent↗
PubMed1996

The Latin American trial of psychosocial support during pregnancy: effects on mother's wellbeing and satisfaction. Latin American Network For Perinatal and Reproductive Research (LANPER).

A randomized controlled trial including 2235 women at high risk of low birthweight was conducted in four Latin American institutions. The objective of this trial was to evaluate a psychosocial support intervention during pregnancy aimed at improving perinatal health and mothers' psychosocial conditions. The core of the intervention was four to six home visits where emotional support, counseling and strengthening of the woman's social network was provided. Outcomes were measured at 36 weeks of pregnancy, post-partum and 40 days after delivery. The intervention was not successful in either altering women's perception of social support and satisfaction with the reproductive experience, as well as maternal and newborn's health care. It is concluded that although high levels of psychosocial distress during pregnancy may play an independent role in determining adverse pregnancy outcomes, this adverse effect does not appear to be ameliorated by psychosocial interventions conducted only during pregnancy, particularly those of a magnitude that can be realistically implemented (in content and frequency) at public care services in most developing countries.

Adolescent↗
PubMed1996

Late assessment of thrombolytic efficacy (LATE) study: prognosis in patients with non-Q wave myocardial infarction. (LATE Study Investigators)

OBJECTIVES: We examined the impact of thrombolytic therapy and the prognosis of patients with non-Q wave myocardial infarction in a randomized placebo-controlled trial known as the Late Assessment of Thrombolytic Efficacy (LATE) study. BACKGROUND: Patients with non-Q wave as compared with Q wave myocardial infarction in the era before thrombolytic therapy were traditionally thought to have a higher rate of reinfarction and death between hospital discharge and 1 year such that the overall prognosis for outcome at 1 year was similar in the two groups. METHODS: The study patients began treatment with either recombinant tissue-type plasminogen activator (rt-PA) or matching placebo, 6 to 24 h after the onset of chest pain. Post hoc analysis of mortality and reinfarction was carried out by comparing rt-PA and placebo in various subsets of patients based on the presenting electrocardiogram (ECG) and the evolution of the ECG with respect to the development of Q waves. RESULTS: Among 5,711 participants, 4,759 had a confirmed myocardial infarction, including 1,309 classified as having a non-Q wave infarction at hospital discharge. Irrespective of treatment assignment, all patients with non-Q wave versus Q wave infarction had a lower 1-year mortality rate (13.3% vs. 17.1%, p = 0.001) and a similar 1-year reinfarction rate (8.6% vs. 7.9%, p = 0.7). Of the 4,759 patients with confirmed myocardial infarction, 2,973 presented with ST segment elevation or bundle branch block, 528 with ST depression and 1,258 with neither ST elevation nor depression. No overall benefit from rt-PA versus placebo with respect to mortality rate at 1 year was seen among patients presenting with ST elevation (21.2% vs. 22.4%, p = 0.5 [90% power to detect 20% relative difference]). Patients with ST elevation who were treated with rt-PA versus placebo <3 h after hospital admission had a lower mortality rate at 1 year (15.8% vs. 19.6%, p = 0.028) than did those treated after 3 h (17.6% vs. 13.0%, p = 0.055). Patients presenting initially with ST depression >2 mm had significant benefit from treatment with rt-PA with respect to 1 year mortality rate (20.1% vs. 31.9%, p = 0.006). CONCLUSIONS: Patients with non-Q wave myocardial infarction constitute a heterogeneous group of patients. Although the observations presented here are limited by post hoc analysis, it is apparent that patients classified as having a non-Q wave infarction after thrombolytic therapy have a better prognosis than do those given placebo. Late admission of thrombolytic therapy (after 6 h) may also be beneficial in patients presenting with ST depression >2 mm and confirmed myocardial infarction. These hypotheses require prospective testing in a larger number of patients.

Electrocardiography↗
PubMed1996

Non-invasive prediction of reperfusion and coronary artery patency by continuous ST segment monitoring in the GUSTO-I trial.

In the GUSTO-I ECG ischaemia monitoring substudy, 1067 patients underwent continuous ST segment monitoring, using vector-derived 12-lead (406 patients), 12-lead (373 patients) and 3-lead Holter (288 patients) ECG recording systems. Simultaneous angiograms at 90 or 180 min following thrombolytic therapy were performed as a part of the prospective study in 302 patients. Infarct vessel patency was established as TIMI perfusion grades 2 or 3 and occlusion as TIMI perfusion grades 0 or 1. Coronary artery patency was predicted from ST trends up to the time of angiography. Predictive values at 90 and 180 min after the start of thrombolysis were 70% and 82% for patency and 58% and 64% for occlusion, respectively. In retrospect, accuracy appeared greatest (79-100%) in patients with extensive ST segment elevation (> or = 400 microV), if both speed of ST recovery and extent of ST segment elevation were taken into account. Although the three recording systems differed considerably in signal processing, no significant difference in accuracy was demonstrated among these systems. We conclude that continuous ECG monitoring may help select high risk patients without apparent reperfusion who may benefit from additional reperfusion therapy. As ST recovery may occur early after the start of thrombolytics and accuracy of the test is related to peak ST levels, the use of on-line ECG monitoring devices on emergency wards and cardiac care units is recommended.

Arteries↗
PubMed1996

PROTECT (Prospective Reinfarction Outcomes in the Thrombolytic Era Cardizem CD Trial): a randomized, double-blind clinical trial of diltiazem versus atenolol in secondary prophylaxis post non-Q wave myocardial infarction.

OBJECTIVE: To describe the rationale and design of the Prospective Reinfarction Outcomes in the Thrombolytic Era Cardizem CD Trial (PROTECT). DESIGN: A multicentre, randomized, double-blind, parallel-group comparison of once daily beta-therapy versus heart rate lowering calcium channel blocker therapy, in the reduction of one-year nonfatal reinfarction and cardiovascular death (combined primary end-point) initiated 24 to 96 h post non-Q wave myocardial infarction. SETTING: One hundred and twenty hospitals across Canada. PATIENTS: Over 7500 women and men aged 21 years or older with enzyme-confirmed non-Q wave infarction and without significant left ventricular systolic dysfunction will be recruited over two years. INTERVENTIONS: Once daily beta-blocker therapy (oral atenolol, 50 to 200 mg) versus once daily calcium channel blocker therapy (oral diltiazem 120 to 360 mg) with follow-up for up to three years. CONCLUSIONS: The PROTECT will be the largest all-Canadian cardiovascular trial to date and will compare two commonly prescribed agents for secondary prophylaxis following non-Q wave infarction. The scientific question addressed by the PROTECT is of major public health importance and the results of the study will directly affect current clinical practice.

Adrenergic beta-Antagonists↗
PubMed1995

Usefulness of ischemic response to mental stress in predicting silent myocardial ischemia during ambulatory monitoring.

To evaluate the relation of mental stress-induced ischemia to silent ischemia on ambulatory monitoring, 46 patients with stable coronary artery disease underwent standardized laboratory mental stress and exercise treadmill testing according to National Institutes of Health protocol during which left ventricular ejection fraction (EF) was determined using the nuclear VEST. Life stress, type A behavior, and hostility were determined using standard interviews. Subsequently, 48-hour ambulatory electrocardiographic monitoring was performed. Twenty-three patients (50%) had an ischemic response (left ventricular EF decrease > or = 5%) to mental stress, which was associated with ambulatory ischemia (13 of 19 with ambulatory ischemia had mental stress-induced ischemia vs 10 of 27 without ambulatory ischemia, p = 0.04). Left ventricular EF response to mental stress was a significant predictor of ambulatory ischemia independent of EF response to exercise (F = 4.8, p = 0.03). Patients with mental stress-induced ischemia had longer total duration (31.4 +/- 57.0 vs 8.3 +/- 18 minutes, p = 0.06) and more frequent episodes of ambulatory ischemia (3.1 +/- 4.6 vs 0.9 +/- 1.9 episodes, p = 0.03). Life stress, type A behavior, and hostility were not associated with prevalence or severity of ambulatory ischemia. In conclusion, an ischemic response to mental stress is significantly associated with higher prevalence, longer duration, and more frequent episodes of ambulatory ischemia.

Aged↗
PubMed1995

Metaiodobenzylguanidine imaging in diabetes mellitus: assessment of cardiac sympathetic denervation and its relation to autonomic dysfunction and silent myocardial ischemia.

OBJECTIVES: This study in patients with diabetes mellitus was undertaken 1) to evaluate cardiac sympathetic innervation in diabetic patients using metaiodobenzylguanidine (MIBG) imaging; 2) to study the relation between autonomic function assessed by clinical maneuvers and abnormalities in MIBG uptake; and 3) to examine the basis for our previous observation of an association between abnormalities in autonomic nervous system dysfunction and silent myocardial ischemia. BACKGROUND: The clinical detection of autonomic dysfunction in diabetes mellitus has been linked to both abnormal perception of pain, including angina, and poor prognosis. METHODS: Uptake of MIBG was measured by dual-isotope imaging in 23 normal subjects and 65 asymptomatic diabetic patients. Silent myocardial ischemia was defined as the presence of a reversible perfusion defect in patients with ST segment depression. RESULTS: The MIBG uptake in the diabetic patients was significantly lower than that in normal subjects in the apex (67 +/- 17% vs. 82 +/- 7%, p = 0.0001), distal third (77 +/- 11% vs. 85 +/- 3%, p = 0.0001), proximal third (77 +/- 9% vs. 84 +/- 3%, p = 0.0001) and base (71 +/- 9% vs. 80 +/- 4%, p = 0.0001) of the left ventricle. Similarly, MIBG uptake was variable across different vascular territories. When MIBG uptake was corrected for perfusion abnormalities, diabetic patients had a greater MIBG uptake defect than normal subjects on visual score assessment (16 +/- 13 vs. 8 +/- 7%, p = 0.0002) and on quantitative MIBG mismatch assessment (13 +/- 15% vs. 2 +/- 2%, p = 0.0001). Diabetic patients with versus without autonomic dysfunction had more extensive MIBG uptake mismatch (17 +/- 17% vs. 4 +/- 6%, p = 0.0001). There was a greater diffuse abnormality in diabetic patients with versus without silent myocardial ischemia detected by sestamibi/MIBG uptake ratio (68 +/- 35% vs. 19 +/- 33%, p = 0.001). CONCLUSIONS: Sympathetic cardiac innervation in normal subjects is inhomogeneous. In contrast to normal subjects, diabetic patients have evidence of a significant reduction in MIBG uptake, most likely on the basis of autonomic dysfunction. Furthermore, diabetic patients with silent myocardial ischemia have evidence of a diffuse abnormality in MIBG uptake, suggesting that abnormalities in pain perception may be linked to sympathetic denervation.

3-Iodobenzylguanidine↗