Search PubMed⌕ Search

Biomedical subjects

R Roberts

Publications and source records attributed to R Roberts.

At least 289 records · Page 16Linked to original sources
PubMed1991

Influence of coronary collateral vessels on myocardial infarct size in humans. Results of phase I thrombolysis in myocardial infarction (TIMI) trial. The TIMI Investigators.

BACKGROUND: The influence of coronary collateral vessels on infarct size in humans remains controversial, partly because no previous study has examined the impact of collaterals present at the onset of acute myocardial infarction on infarct size. METHODS AND RESULTS: The present study used the data base of the Thrombolysis in Myocardial Infarction (TIMI) Phase I trial to correlate the presence or absence of angiographically documented collaterals in the initial hours of myocardial infarct evolution with the size of the infarct as assessed by serial measurements of serum creatine kinase (CK). To avoid the confounding effects of reperfusion on enzymatic estimates of infarct size, this report is limited to those 125 patients who failed to recanalize at 90 minutes after administration of tissue plasminogen activator or streptokinase. Patients with angiographically documented collaterals (group A, n = 51) had significantly lower values of peak serum CK than patients without collaterals (group B, n = 74) (1,877 +/- 216 versus 2,661 +/- 212 IU/l, respectively [mean +/- SEM], p = 0.004). Similarly, CK-derived infarct size estimates were significantly lower in group A than in group B (20.6 +/- 2.5 versus 31.4 +/- 2.8 CK gram equivalents, p = 0.001). The infarct size observed in patients with collaterals was less for anterior infarctions as well as for infarctions of other locations; thus, the beneficial effects of collaterals were independent of the site of the infarct. In 65 of the 125 patients who failed to reperfuse, left ventricular ejection fraction (LVEF) was assessed by contrast ventriculography both at initial cardiac catheterization (before thrombolytic therapy) and at hospital discharge. Among the patients who had both studies, global LVEF tended to increase from pretreatment to hospital discharge in group A (from 50.6 +/- 1.8% to 53.4 +/- 1.8%, p = 0.10) but decreased in group B patients (from 50.3 +/- 1.8% to 47.8 +/- 1.7%, p = 0.02). At hospital discharge, global LVEF was greater in patients with coronary collaterals (53.5 +/- 1.7% versus 49.6 +/- 1.7%, p = 0.01). CONCLUSIONS: The results demonstrate that, in patients in whom thrombolytic therapy fails to induce reperfusion, the presence of coronary collateral vessels at the onset of myocardial infarction is associated with limitation of infarct size as assessed enzymatically and with improved ventricular function on discharge as assessed by LVEF.

Collateral Circulation↗
PubMed1991

Localization of gene for familial hypertrophic cardiomyopathy to chromosome 14q1 in a diverse US population.

BACKGROUND: Familial hypertrophic cardiomyopathy, an inherited primary cardiac abnormality characterized by ventricular hypertrophy, is the leading cause of sudden death in the young. Recent application of restriction fragment length polymorphism markers has provided provocative results, with localization to chromosome 18 (Japanese studies), 16 (Italian studies), 14 (US and French-Canadian studies), and two (National Institutes of Health studies) indicating genetic heterogeneity. Interpretation remains speculative until at least one of these loci is confirmed in unrelated pedigrees by independent investigators. METHODS AND RESULTS: We studied eight unrelated families of varied ethnic origins across the United States. DNA from each individual was digested with restriction enzymes TaqI or BamHI and analyzed by Southern blots followed by hybridization with probes T cell receptor alpha (TCRA), myosin heavy chain beta, D14S25, and D14S26. Multipoint linkage analysis showed a maximum lod score of 4.3, placing the locus 10 cM from D14S26 between D14S26 and TCRA, with an odds ratio of 20,000:1 and 90% confidence limits of 12 cM proximal to D14S25 to 4 cM distal to TCRA. The probability of linkage to 14q1 was more than 99%. CONCLUSIONS: These results indicate that the loci for familial hypertrophic cardiomyopathy in our families is primarily 14q1 but does not exclude other loci in a small proportion of the families. Thus, 14q1 appears to be the locus for familial hypertrophic cardiomyopathy in a significant proportion of the US population.

Cardiomyopathy, Hypertrophic↗
PubMed1991

Post-myocardial infarction mortality in patients with ventricular premature depolarizations. Canadian Amiodarone Myocardial Infarction Arrhythmia Trial Pilot Study.

BACKGROUND: Among survivors of acute myocardial infarction, frequent and repetitive ventricular premature depolarizations (VPDs) detected on ambulatory monitoring contribute independently to the risk of all-cause mortality and sudden death. Apart from the beta-blockers, no antiarrhythmic drug has been reliably demonstrated to reduce mortality among patients with VPDs. A pilot study was undertaken to gather data to aid in the design of a multicenter trial of amiodarone for the reduction of mortality from cardiac arrhythmias in such patients. METHODS AND RESULTS: Seventy-seven patients with acute myocardial infarction within the previous 6-30 days and 10 or more VPDs/hr or one or more runs of ventricular tachycardia on 24-hour electrocardiographic recording were randomized in a double-blind fashion in a 2:1 amiodarone-to-placebo ratio. The loading dose was 10 mg/kg/day for 3 weeks. The maintenance dose was 300-400 mg/day with reductions at 4-month intervals in response to VPD suppression, excessive plasma levels, or toxicity. VPD suppression at 1 week and 2 weeks was 63% and 85%, respectively, on amiodarone and 17% and 27%, respectively, on placebo. Apart from thyroid-stimulating hormone elevation and skin reactions, no side effects occurred more frequently with amiodarone. The study drug was stopped for side effects or noncompliance in 35% of amiodarone patients and 34% of placebo patients. Patients were followed for a maximum of 2 years (mean, 20 months). Arrhythmic death or resuscitated ventricular fibrillation occurred in two of 48 amiodarone patients (6%) and four of 29 placebo patients (14%), whereas the rates of all-cause mortality were five of 48 (10%) and six of 29 (21%), respectively. CONCLUSIONS: Amiodarone, in moderate loading and maintenance dosages with adjustments in response to plasma levels, VPD suppression, and side effects, results in effective VPD suppression and acceptable levels of toxicity.

Amiodarone↗
PubMed1991

Effects of inosine on glycolysis and contracture during myocardial ischemia.

The effects of inosine (INO) on substrate metabolism and rigor formation in ischemic myocardium were examined in isolated rabbit hearts. Metabolite content was assessed in tissue extracts by chemical analysis and in the whole heart by 13C and 31P nuclear magnetic resonance spectroscopy. In ischemic hearts metabolizing either [3-13C]pyruvate or [1-13C]glucose, 1 mM INO increased both total and 13C-labeled alanine content; lactate content was unaffected. At 3 minutes of ischemia, tissue alanine was 1.81 +/- 0.11 microM/g wet wt (mean +/- SEM) in hearts perfused with pyruvate+INO versus 1.23 +/- 0.15 microM/g wet wt in hearts perfused with pyruvate alone (p less than 0.05). INO reduced tissue glycogen during ischemia in pyruvate-perfused hearts. Tissue alanine content in ischemic hearts that were supplied glucose+INO (1.29 +/- 0.13 microM/g wet wt) was greater than in ischemic hearts supplied glucose alone (0.65 +/- 0.14 microM/g wet wt). Alanine was found to originate from pyruvate and was a glycolytic end product in glucose-perfused hearts. INO raised the [3-13C]alanine/[3-13C]lactate ratio in ischemic, intact hearts (glucose = 0.24 +/- 0.07 versus glucose+INO = 0.60 +/- 0.09; pyruvate = 0.49 +/- 0.08 versus pyruvate+INO = 0.89 +/- 0.08). At 7 minutes of ischemia, ATP content fell to 70 +/- 3% with glucose+INO versus 58 +/- 5% with glucose alone. Rigor (stone heart) was delayed from 14.7 +/- 1.3 to 23.2 +/- 1.6 minutes with INO. INO did not change ATP content in ischemic hearts that were supplied pyruvate but delayed rigor (pyruvate = 9.9 +/- 1.2 minutes; pyruvate+INO = 15.6 +/- 1.0 minutes), possibly at the expense of glycogen. Supplemental glucose improved the effectiveness of INO with pyruvate to preserve ATP (pyruvate+glucose = 42 +/- 6%; pyruvate+glucose+INO = 72 +/- 6%) and further delayed rigor (pyruvate+glucose = 13.3 +/- 1.5 minutes; pyruvate+glucose+INO = 20.3 +/- 1.8 minutes). Glucose metabolism supported improved energetic and contractile states in ischemic hearts treated with INO. Thus, cardioprotection of the ischemic heart by INO was associated with preservation of functional integrity and improved energy production due to increased glycolytic activity. Activation of glycolysis in the presence of INO was accommodated by augmented alanine production without the additional accumulation of lactate.

Alanine↗
PubMed1991

The vascular smooth muscle alpha-actin gene is reactivated during cardiac hypertrophy provoked by load.

Cardiac hypertrophy triggered by mechanical load possesses features in common with growth factor signal transduction. A hemodynamic load provokes rapid expression of the growth factor-inducible nuclear oncogene, c-fos, and certain peptide growth factors specifically stimulate the "fetal" cardiac genes associated with hypertrophy, even in the absence of load. These include the gene encoding vascular smooth muscle alpha-actin, the earliest alpha-actin expressed during cardiac myogenesis; however, it is not known whether reactivation of the smooth muscle alpha-actin gene occurs in ventricular hypertrophy. We therefore investigated myocardial expression of the smooth muscle alpha-actin gene after hemodynamic overload. Smooth muscle alpha-actin mRNA was discernible 24 h after coarctation and was persistently expressed for up to 30 d. In hypertrophied hearts, the prevalence of smooth muscle alpha-actin gene induction was 0.909, versus 0.545 for skeletal muscle alpha-actin (P less than 0.05). Ventricular mass after 2 d or more of aortic constriction was more highly correlated with smooth muscle alpha-actin gene activation (r = 0.852; P = 0.0001) than with skeletal muscle alpha-actin (r = 0.532; P = 0.009); P less than 0.0005 for the difference in the correlation coefficients. Thus, smooth muscle alpha-actin is a molecular marker of the presence and extent of pressure-overload hypertrophy, whose correlation with cardiac growth at least equals that of skeletal alpha-actin. Induction of smooth muscle alpha-actin was delayed and sustained after aortic constriction, whereas the nuclear oncogenes c-jun and junB were expressed rapidly and transiently, providing potential dimerization partners for transcriptional control by c-fos.

Actins↗
PubMed1991

Reliability of a Standardized Mini-Mental State Examination compared with the traditional Mini-Mental State Examination.

OBJECTIVE: The objective of this study was to compare the reliability of the Mini-Mental State Examination with that of a new Standardized Mini-Mental State Examination, which has expanded guidelines for administration and scoring. METHOD: The subjects were 32 stable elderly residents of a nursing home and 16 elderly residents of a chronic care hospital unit. Six raters administered the Folstein Mini-Mental State to 22 of these stable elderly subjects, and five raters administered the standardized version to 26 of these subjects. Each subject was tested on three different occasions 1 week apart. Each rater tested 4-6 subjects at the first and third weeks and 4-6 different subjects at the second week. The analytic technique used was one-way analysis of variance to estimate the interrater variance and the intrarater variance. RESULTS: The intrarater variance on all occasions was reduced by 86% and the interrater variance was reduced by 76% when the Standardized Mini-Mental State was used; the reductions in variance were significant (p less than 0.003). The intraclass correlation for the Mini-Mental State was 0.69; for the standardized version it was 0.90. It took less time to administer the Standardized Mini-Mental State than the Mini-Mental State. CONCLUSIONS: The Standardized Mini-Mental State had better reliability than the Mini-Mental State in this study group. Although the improved reliability of the Standardized Mini-Mental State was achieved by reducing measurement noise, this advantage would likely occur in a broad spectrum of patients.

Aged↗
PubMed1991

When is a prognostic factor useful? A guide for the perplexed.

Traditionally, a number of variables have been used to predict outcome in patients with early-stage breast cancer. These tests are simple to perform and relatively inexpensive. Recently, a number of new factors, eg, tumor proliferative index, nuclear DNA content, and amplification or overexpression of growth-promoting genes or oncogenes have been identified as potential predictors of outcome in patients with breast cancer. There is now increasing pressure to introduce such tests into routine clinical practice. How does a clinical practitioner identify which test, or group of tests, best predicts adverse outcome and whether any more clinically useful information is provided than with the use of more traditional factors alone? The aim of a prognostic test in breast cancer is to predict which patients are destined to develop a recurrence of cancer and those who are not. The prognostic usefulness of a test can be expressed in terms of relative risk (RR), which is the ratio of the risk of breast cancer recurrence in patients who test positive to the risk in those who test negative. Methodologic guidelines that should be satisfied by a study evaluating the predictive ability of a test include the following: (1) Was an inception cohort assembled? (2) Was the referral pattern described? (3) Were laboratory and clinical outcomes assessed in a blinded fashion? (4) Was complete follow-up achieved? (5) Was adjustment for extraneous prognostic factors carried out? (6) Were appropriate statistical methods used? An approach is suggested to help the clinician choose the test, or combination of tests, likely to discriminate between "high-" and "low-risk" patients in his/her own practice. The decision regarding what particular threshold value (risk) defined by a prognostic test (or series of tests) warrants adjuvant therapy for an individual patient is a complex one but should be based on a clear presentation of the risks and benefits to the patient.

Breast Neoplasms↗
PubMed1991

A standard heparin nomogram for the management of heparin therapy.

A nomogram for the adjustment of heparin dosage was developed to standardize heparin therapy and to reduce delays in achieving and maintaining a therapeutic activated partial thromboplastin time (APTT) result. Fifty consecutive patients with acute venous thromboembolism had their continuous intravenous heparin therapy adjusted according to this heparin nomogram. The effect of the nomogram on heparin therapy in these patients was compared with data from 53 historical control patients. The proportion of patients in the nomogram group who reached a therapeutic APTT at 24 hours after the start of heparin therapy was 66%, which increased to 81% at 48 hours. In contrast, 37% and 58% of the control patients reached a therapeutic APTT at 24 and 48 hours, respectively. The percentage of therapeutic APTT results of the total number of APTT determinations was greater in the nomogram patients than controls. The use of this heparin nomogram resulted in (1) achieving a therapeutic APTT at 24 and 48 hours in a large proportion of patients and (2) reduced periods of inadequate anticoagulation and overanticoagulation during heparin therapy.

Aged↗
PubMed1991

Modulation of cardiac genes by mechanical stress. The oncogene signalling hypothesis.

In cardiac muscle, the selectivity and specificity of gene regulation by heparin-binding and transforming growth factors resembles the characteristic program of fetal gene induction during myocardial hypertrophy produced by load. Shared by isolated cardiac myocytes and intact hearts, these complex and heterogeneous responses provide intriguing systems, which are distinct from other lineages and models of cell growth, for the study of trophic signal transduction by cellular oncogenes. A functional role for peptide growth factors and other oncogene-encoded proteins in myocardial hypertrophy suggests biological pathways which might usefully be exploited to promote compensatory growth following infarction or to interfere with maladaptive changes during a hemodynamic load.

Actins↗
PubMed1991

Development and clinical performance of an automated, portable tungsten-178/tantalum-178 generator.

An automated, portable 178W/178Ta generator system has been developed for use in first-pass radionuclide angiography studies with the multiwire gamma camera. Eluant (0.03N HCI, 0.1% H2O2) and buffer (0.13 N Na2HPO4) are delivered with a dual channel peristaltic pump. The generator column is a borosilicate glass tube with 30 microns fused glass frit containing 0.75 ml AG1X8 anion exchange resin. This column and associated plumbing are assembled, integrally autoclaved, and then connected to sterile eluant and buffer containers. Automatic push-button elution directly into an injection syringe is provided. Three such generators have been employed in the study of 78 patients in the catheterization laboratory utilizing a mobile, multiwire gamma camera. Over a 3-mo period, 301 sterile pyrogen-free doses ranging from 15 to 99.5 mCi were supplied with a mean breakthrough level of 2.1 +/- 3.6 microCi. This automated, portable, high-yield 178W/178Ta generator represents a major advancement that will significantly facilitate first-pass radionuclide angiography with 178Ta and the multiwire gamma camera.

Angioplasty, Balloon, Coronary↗
PubMed1990

A comparison between heparin and low-dose aspirin as adjunctive therapy with tissue plasminogen activator for acute myocardial infarction. Heparin-Aspirin Reperfusion Trial (HART) Investigators.

BACKGROUND: We report the results of the Heparin-Aspirin Reperfusion Trial, a collaborative study comparing early intravenous heparin with oral aspirin as adjunctive treatment when recombinant tissue plasminogen activator (rt-PA) is used for coronary thrombolysis during acute myocardial infarction. METHODS: Two hundred five patients were randomly assigned to receive either immediate and then continuous intravenous heparin (starting with a 5000-unit bolus; n = 106) or immediate and then daily oral aspirin (80 mg; n = 99) together with rt-PA (100 mg intravenously over a six-hour period) initiated within six hours of the onset of symptoms. We evaluated the patency of the infarct-related artery by angiography 7 to 24 hours after beginning rt-PA infusion, the frequency of reocclusion of the artery by repeat angiography on day 7, and ischemic or hemorrhagic complications during the hospital stay. RESULTS: At the time of the first angiogram, 82 percent of the infarct-related arteries in the patients assigned to heparin were patent, as compared with only 52 percent in the aspirin group (P less than 0.0001). Of the initially patent vessels, 88 percent remained patent after seven days in the heparin group, as compared with 95 percent in the aspirin group (P not significant). The numbers of hemorrhagic events (18 in the heparin and 15 in the aspirin group) and recurrent ischemic events (8 in the heparin and 2 in the aspirin group) were similar in the two groups. CONCLUSIONS: Coronary patency rates associated with rt-PA are higher with early concomitant systemic heparin treatment than with concomitant low-dose oral aspirin. This observation has important implications for clinical practice and should be considered in the design and interpretation of clinical trials involving coronary thrombolytic therapy.

Administration, Oral↗
PubMed1990

Impairment of endothelium-dependent arterial relaxation by lysolecithin in modified low-density lipoproteins.

Atherosclerosis in animals and humans is associated with an unresponsiveness of arteries and arterioles to endothelium-dependent vasodilators--agents acting on smooth muscle indirectly by stimulating the release from endothelial cells of a vasodilator principle (endothelium-derived relaxing factor). Altered vasomotor regulation in atherosclerosis could partly reflect an injurious action of abnormal lipoproteins on endothelium. Recently, 'cell-modified' or 'oxidized' low-density lipoprotein (EC-LDL) has received increasing attention because of its potential cytotoxic and atherogenic properties. We report here that arteries exposed to EC-LDL in vitro show an endothelium-dependent vasoregulatory impairment closely resembling that of atherosclerotic arteries. Our results indicate that transfer of lysolecithin from EC-LDL to endothelial membranes produces a selective unresponsiveness to receptor-regulated endothelium-dependent vasodilators.

Acetylcholine↗
PubMed1990

Frequency and significance of late evolution of Q waves in patients with initial non-Q-wave acute myocardial infarction. Diltiazem Reinfarction Study Group.

Serial 12-lead electrocardiogram and plasma creatine kinase (CK)-MB values from 544 patients with confirmed non-Q-wave acute myocardial infarction (AMI) were analyzed to define the rate of progression of non-Q-wave AMI to Q-wave AMI and to examine its relation to CK-MB evidence of extension. The baseline electrocardiogram was obtained 50 +/- 10 hours after AMI and compared with subsequent electrocardiograms at 48 and 72 hours after baseline record and at discharge. Plasma CK-MB was assayed every 12 hours after baseline. A total of 76 patients (14%) progressed to Q-wave AMI. Compared to the 468 patients who retained non-Q-wave AMI, those patients who evolved Q-wave AMI were more likely to exhibit ST elevation greater than or equal to 1.0 mm in greater than or equal to 2 infarct-related leads (49 vs 32%, p less than 0.005), higher peak CK values with the index AMI (754 +/- 625 vs 611 +/- 604 IU; p = 0.0018) and a greater incidence of CK-MB-confirmed extensions (18.5 vs 5.5%, p less than 0.0001). For those patients progressing to Q-wave AMI within 48 hours of baseline electrocardiogram, CK-MB extension occurred in 9.5% (4 of 42) versus 29.4% (10 of 34) of those who progressed after 48 hours (p = 0.0262). A distinct minority (14%) of patients with non-Q-wave AMI will develop Q waves before discharge. The progression to Q-wave AMI after initial non-Q-wave AMI appears to involve 2 different mechanisms: temporal lag in the electrocardiogram, and actual extension by quantitative CK-MB criteria.

Creatine Kinase↗
PubMed1990

A novel chromatographic resolution of 21-hydroxysteroid metabolites of progesterone.

21-Hydroxysteroid metabolites of both progesterone and deoxycorticosterone are excreted in rabbit urine and are eluted from an alumina adsorption column after 21-deoxysteroids. The separation is independent of polarity and dependent on the interaction of the 21-hydroxyl function with the adsorbent. The group separation of these steroids allowed further analysis by high performance liquid chromatography and revealed different proportions of metabolites. This is the first report of the excretion of 21-hydroxysteroid metabolites of progesterone in rabbit urine.

Aluminum Oxide↗
PubMed1990

Differential risk patterns associated with 3 month as compared with 3 to 12 month mortality and reinfarction after non-Q wave myocardial infarction. The Diltiazem Reinfarction Study Group.

Follow-up data for 515 survivors of acute non-Q wave myocardial infarction were categorized according to mortality: 1) between hospital discharge and 3 months after infarction (early), and 2) between 3 and 12 months after infarction (late). The mortality rate decreased steadily for the first 3 months and was constant thereafter. There were 25 early and 32 late deaths. After adjustment for the longer time associated with the 3 to 12 month period, the relative risk per unit time of early as compared with late mortality was 2.64. Risk factors for early mortality were different from those that predicted late mortality. Independent predictors of mortality between hospital discharge to 3 months after infarction were ST segment depression that persisted during hospitalization (p less than 0.0001), in-hospital reinfarction (p = 0.0006) and a history of congestive heart failure (p = 0.0255). Persistent ST depression and in-hospital reinfarction had neither a univariate nor an independent association with 3 to 12 month mortality. Age (p less than 0.0001), reinfarction between discharge and 3 months (p = 0.0147) and diabetes (p = 0.0404) were independently associated with late mortality. Early mortality was only 0.5% (1 of 199) in patients with no ST depression at either baseline or discharge (group 1); 4.8% (8 of 168) in those with ST depression at exactly one time point (group 2) and 13.7% (16 of 117) in those who had ST depression present at both time points (group 3). All pairwise differences were significant (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Double-Blind Method↗