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R Roberts

Publications and source records attributed to R Roberts.

At least 415 records · Page 23Linked to original sources
PubMed1986

Isolation and sequence analysis of a full-length cDNA for human M creatine kinase.

A full length cDNA for human M creatine kinase has been isolated and sequenced. The cDNA contains 77 bp of 5' untranslated, 338 bp of 3' untranslated sequence and the entire coding region (1146 bp) for human M creatine kinase. The M creatine kinases from different species share considerable sequence homology within the coding region (77-91%) and in amino acid sequence (82-97%). Little or no sequence homology is observed in the 3' untranslated sequence of the mammalian M creatine kinases, although canine and human creatine kinase share overall 80% sequence homology in 5' untranslated sequence. A unique 8 bp sequence was identified in the 5' untranslated regions of mammalian M creatine kinase but is not present in B creatine kinase cDNA. The degree of sequence conservation observed implies an evolutionary constraint on M creatine kinase structure beyond that which would be expected for the maintenance of enzymatic function.

Amino Acid Sequence↗
PubMed1986

Determining optimal therapy--randomized trials in individual patients.

Although the treatment of an individual patient in routine clinical practice has been likened to an experiment, the method is so susceptible to bias that we have come to demand multi-patient, double-blind, randomized controlled trials on matters of efficacy. Unfortunately, such trials have not or cannot be carried out for many clinical disorders; even when they have been executed their results may be difficult to extrapolate to individual patients. To resolve this problem, we have begun to use double-blind randomized trials in which a single patient undergoes a series of pairs of treatments, consisting of one active and one placebo or alternative treatment per pair, with the order determined by random allocation. Appropriate treatment targets (signs, symptoms, or laboratory tests) are used as the measure of efficacy, and the trial is continued until efficacy is established or disproved. We describe such a trial, which resulted in a dramatically beneficial modification of treatment in a patient with partially reversible airflow limitation. We have established a clinical service that facilitates the widespread use of the method in our community.

Aged↗
PubMed1986

Sudden death and its relation to QT-interval prolongation after acute myocardial infarction: two-year follow-up.

Risk of sudden death was assessed in 533 patients who survived 10 days after acute myocardial infarction (AMI) and were followed for up to 24 months (mean 18) in the Multicenter Investigation of the Limitation of Infarct Size. Analysis of clinical and laboratory variables measured before hospital discharge revealed that the QT interval, either corrected (QTc) or uncorrected for heart rate, did not contribute significantly to prediction of subsequent sudden death or total mortality. In this population, frequent ventricular premature complexes (more than 10 per hour) on ambulatory electrocardiographic monitoring and left ventricular (LV) dysfunction (radionuclide LV ejection fraction of 0.40 or less) identify patients at high risk of sudden death. In patients with these adverse clinical findings, the QTc was 0.468 +/- 0.044 second among those who died suddenly and 0.446 +/- 0.032 second in survivors, and was not statistically significant as an additional predictor of sudden death. Consideration of the use of type I antiarrhythmic agents, digoxin, presence of U waves and correction for intraventricular conduction delay did not alter these findings. Although QT-interval prolongation occurs in some patients after acute myocardial infarction, reduced LV ejection fraction and frequent ventricular premature complexes are the most important factors for predicting subsequent sudden death in this patient population.

Adrenergic beta-Antagonists↗
PubMed1986

Effect of inflation pressures on coronary angioplasty balloons.

It is a common conception that the balloons used in percutaneous transluminal coronary angioplasty will inflate to a certain designated diameter and maintain this diameter over the wide range of inflation pressures. With use of an optical magnification system, the diameters of multiple angioplasty dilating catheters made of polyvinyl chloride (USCI) and polyethylene (Advanced Cardiovascular System, Inc.) were measured with designated balloon diameter sizes of 2.0 to 3.7 mm. All balloons had a linear increase in diameter over a range of pressures from 2 to 10 atm. The average increase in diameter over this pressure range was 15% (range 7 to 18%). Polyvinyl chloride balloons reached their specified diameter at less than 5 atm and exceeded it at higher inflation pressures. Polyethylene balloons reached their specified diameter at 8 to 10 atm, and were below specified diameters at lower pressures. There was slight variation in size and only a minimal difference in compliance between balloons of the same material and size. A given balloon achieved the same diameter at a given pressure even after multiple inflations and maintained a stable diameter during prolonged inflations.

Angioplasty, Balloon↗
PubMed1986

Transluminal coronary angioplasty in the elderly.

The safety and clinical efficacy of percutaneous transluminal coronary angioplasty (PTCA) in elderly patients has not been established. Of 639 PTCAs performed between March 1980 and May 1984, 119 patients were 65 years or older (mean 70 years). On angiography, elderly patients differed only in the more frequent occurrence of visible calcific deposits (26% vs 8% in younger patients, p less than 0.01). Primary success was achieved in 81%, vs 80% in patients younger than 65 years. Major complication rates were comparable to those of younger patients: emergency coronary artery bypass surgery, 4.1% vs 4.7%; acute myocardial infarction, 2.5% vs 2.9%; and death, 0.8% vs 0. Late clinical follow-up ranging from 5 to 50 months (mean 18) showed that symptomatic improvement was achieved in 91% of patients in whom PTCA was successful, with 55% being asymptomatic. Seventy percent of patients were as active or more active (30%) than before PTCA and 47% were taking fewer medications. Four late deaths occurred, none from cardiac causes. These data support the safety and clinical effectiveness of PTCA in elderly patients and justify the extension of indications for PTCA to selected patients with multivessel disease in this age group.

Aged↗
PubMed1986

Hemodynamic effects of moricizine at rest and during supine bicycle exercise: results in patients with ventricular tachycardia and left ventricular dysfunction.

To evaluate the hemodynamic effects of moricizine, 20 patients with frequent nonsustained ventricular tachycardia (VT) with a mean left ventricular ejection fraction (EF) of 39 +/- 14% were enrolled in a prospective single-blind, placebo-controlled study. Hemodynamic measurements were performed at rest and during supine bicycle exercise on placebo and moricizine therapy (10 mg/kg/day). Although 16 of 19 patients experienced no rest or exercise deterioration in hemodynamic parameters during drug dosing, three patients had acute deterioration of pulmonary capillary wedge pressure and cardiac index (CI) on moricizine. During follow-up of 6 +/- 3 months, two subgroups were identified: 10 of 19 patients had effective long-term reduction in VT, whereas 9 of 19 patients had poor control of ventricular arrhythmia or congestive heart failure and were discontinued from the trial. Baseline EF and hemodynamic parameters at rest were similar in both patient subgroups. However, protocol dropouts had a hemodynamic response to exercise on moricizine that was significantly depressed as compared to patients with a favorable antiarrhythmic outcome (p less than 0.02). The following hemodynamic profile characterizes patients unlikely to have an antiarrhythmic response to moricizine: an increase in CI of less than 1.0 L/min/m2 and no increase in left ventricular stroke work index during supine exercise.

Exercise Test↗
PubMed1986

Complex ventricular arrhythmias associated with the mitral valve prolapse syndrome. Effectiveness of moricizine (Ethmozine) in patients resistant to conventional antiarrhythmics.

On the basis of epidemiologic studies, more than 10 million Americans have echocardiographic evidence of mitral valve prolapse. Although ventricular arrhythmias occur frequently (over 50 percent of patients with mitral valve prolapse), they rarely result in sustained ventricular tachycardia or sudden cardiac death. However, a common problem in clinical practice is a patient with mitral valve prolapse and symptomatic complex ventricular arrhythmias refractory or intolerant to both beta blockers and conventional type I antiarrhythmics. These drugs are known to have frequent side effects, toxicity, and proarrhythmic effects. In 17 patients with mitral valve prolapse who presented with symptomatic complex ventricular arrhythmias and who were unresponsive to an average of the three conventional agents, moricizine (Ethmozine) was effective in suppressing 90 percent of ventricular premature depolarizations, 99 percent of nonsustained runs of ventricular tachycardia, as well as all sustained runs of ventricular tachycardia, resulting in abolition of palpitations, dizziness, and syncopal episodes. Its efficacy as well as its low frequency of minor side effects makes it ideal for future consideration in the population with mitral valve prolapse, who are frequently young and may therefore require therapy for many years.

Adult↗
PubMed1986

Quantitative analysis of thallium-201 uptake and washout before and after transluminal coronary angioplasty.

Transluminal coronary angioplasty has become an important therapeutic modality in the treatment of coronary artery disease. The effects of coronary angioplasty on regional myocardial perfusion have been reported in only a small series of patients, employing subjective analysis of thallium-201 perfusion scintigrams. Thus, we studied 61 patients with quantitative analysis of thallium-201 uptake and washout before and after undergoing angioplasty. Prior to angioplasty, there were 105 areas in 47 patients with abnormal thallium-201 uptake during exercise, with a mean uptake of 49 +/- 1.3%. The uptake of thallium-201 in these same areas increased to 71.3 +/- 1.9% post angioplasty (P less than 0.0001), and 68 (65%) of the areas showing abnormal uptake returned to normal. Abnormalities in washout of thallium-201 before angioplasty were seen more frequently than in uptake (150 vs 105 areas, P less than 0.05), with 8 patients having abnormal washout in the presence of totally normal uptake. Thallium-201 washout in the abnormal areas improved from 16 +/- 2.8 pre angioplasty to -23 +/- 1.8% post angioplasty (P less than 0.001). Normalization resulted in 6 of the 8 patients with exclusively washout abnormality. Residual abnormalities in uptake and/or washout were seen in 53% of the patients, usually in areas with prior myocardial infarction or supplied by a vessel with significant stenosis which did not undergo angioplasty. Improved thallium-201 uptake and washout corresponded to reductions in percent coronary area stenosis (89 +/- 1.0 to 36 +/- 2.0%, P less than 0.001) and transstenotic pressure gradient (42 +/- 3.0 to 9.0 +/- 2.0 mm Hg, P less than 0.001). Thus, quantitative analysis of thallium-201 uptake and washout provided objective evidence for improved myocardial perfusion after coronary angioplasty. Due to a fairly high prevalence of residual perfusion abnormalities after this procedure, optimal assessment of benefits requires quantitative comparison of thallium uptake and washout before and after coronary angioplasty.

Adult↗
PubMed1986

Disparity of reperfusion arrhythmias after reversible myocardial ischemia in open chest and conscious dogs.

Myocardial reperfusion after brief, reversible ischemia is frequently associated with malignant arrhythmias in experimental animals. These observations have been extrapolated to humans despite being restricted to anesthetized, open chest preparations. No data are available regarding the incidence of reperfusion arrhythmias after reversible (less than 20 minutes) ischemia in the conscious state. Thus, reperfusion arrhythmias after a 15 minute occlusion of the left anterior descending coronary artery were compared in 24 open chest dogs (17 anesthetized with pentobarbital and 7 with chloralose plus urethane) and 25 conscious, unsedated, trained dogs. The incidence of all rhythm disorders (single premature ventricular complexes, pairs, ventricular tachycardia and fibrillation) was markedly and significantly lower in conscious than in either pentobarbital- or chloralose-anesthetized dogs. The disparity was not accounted for by differences in coronary collateral flow, coronary reactive hyperemia or occluded bed size. The conscious animals, however, exhibited lower heart rates and arterial pressures during reperfusion than did the open chest dogs, suggesting a lower level of adrenergic stimulation, which might have contributed to the reduced incidence of reperfusion arrhythmias. Coronary reperfusion after 15 minutes of occlusion is unlikely to precipitate ventricular tachyarrhythmias in the conscious, trained dog, even after severe ischemia. The occurrence of these rhythm disorders in anesthetized models may reflect the influence of surgical trauma or excessive adrenergic activity, or both. Reperfusion arrhythmias after reversible ischemia may be considerably less common in the clinical setting than previously postulated on the basis of open chest animal experiments.

Anesthesia↗
PubMed1986

N-2-mercaptopropionylglycine improves recovery of myocardial function after reversible regional ischemia.

Myocardial reperfusion after reversible regional ischemia is known to result in delayed recovery of contractile function, but the mechanism responsible for this phenomenon remains unclear. We examined the ability of N-2-mercaptopropionylglycine, a synthetic thiol compound with oxygen free radical scavenging properties, to attenuate postischemic dysfunction in open chest dogs undergoing a 15 minute occlusion of the left anterior descending coronary artery followed by 4 hours of reperfusion. Treated animals received an infusion of N-2-mercaptopropionylglycine (50 mg/kg per h) for 4 hours starting 15 minutes before coronary occlusion. Collateral flow, as determined with radioactive microspheres after 10 minutes of ischemia, was 0.07 +/- 0.01 ml/min per g (mean +/- SE) in both control (n = 20) and treated (n = 13) groups. The occluded vascular bed, as determined by postmortem perfusion, averaged 26.1 +/- 1.2% of the weight of the left ventricle in control and 29.6 +/- 1.3% in treated animals. Systolic wall thickening (an index of regional function) was assessed with an epicardial pulsed Doppler probe. The two groups exhibited comparable systolic thickening under baseline conditions and similar degrees of dyskinesia during ischemia. Nevertheless, recovery of function (expressed as percent of baseline) was considerably greater in the treated dogs at 1 hour (44.6 versus 12.8%, p = 0.05), 2 hours (64.0 versus 31.6%, p less than 0.02), 3 hours (77.1 versus 36.7%, p less than 0.01) and 4 hours of reperfusion (75.0 versus 40.0%, p less than 0.05). Thus, N-2-mercaptopropionylglycine produced a significant and sustained improvement in recovery of contractile function after a brief episode of regional myocardial ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids, Sulfur↗
PubMed1986

Influence of alcohol and caffeine consumption on caffeine elimination.

Ten healthy male volunteers were each studied on four separate occasions to assess the role of regular caffeine and alcohol intake on caffeine elimination. Antipyrine disappearance was also studied as an established quantitative test of hepatic microsomal function. Regular caffeine intake in high doses for 1 week failed to alter either antipyrine or caffeine pharmacokinetics. In contrast, alcohol intake of 50 g/day significantly prolonged caffeine half-life by 72% (P less than 0.005) and diminished caffeine clearance by 36% (P less than 0.0005). However, antipyrine kinetics were unaltered. These results demonstrate that alcohol, in amounts commonly consumed, is a strong inhibitor of caffeine metabolism.

Adult↗
PubMed1986

Dissociated expression of c-myc and a fos-related competence gene during cardiac myogenesis.

Cardiac myocytes irreversibly lose their proliferative capacity soon after birth, and cardiac DNA synthesis becomes uncoupled from mitotic division. Therefore, we examined cardiac muscle for developmental down regulation of inducible proto-oncogenes associated with cell proliferation. c-myc mRNA decreased continuously from day 13 of embryonic development and was dissociated from expression of the fos-related gene r-fos, which decreased precipitously between days 3 and 7 after birth.

Animals↗
PubMed1986

Myocardial infarct size quantification by MR imaging early after coronary artery occlusion in dogs.

The feasibility of using magnetic resonance (MR) imaging to estimate myocardial infarct size was explored in an in vitro model using only the inherent differences in contrast between infarcted and noninfarcted myocardium. Eight dogs underwent coronary occlusion; their hearts were removed 6 hours later. Estimates of T2 for normal and infarcted myocardium were derived from MR images. Infarct size was quantified anatomically using triphenyltetrazolium-chloride (TTC) staining and compared with MR estimates. The T2 values derived from the images clearly discriminated between infarcted (126 +/- 22 msec) and normal myocardium (88 +/- 10 msec, P less than .05), providing images with good contrast between normal and infarcted myocardium. Comparable differences in T2 values were also noted from spectrometric determinations. Estimates of infarct size by MR imaging compared well with TTC estimates (r = 0.98) over a wide range of infarct sizes from 3% to 29% of the left ventricular mass. These results suggest the potential for in vivo quantification of infarct size based on the inherent contrast difference between infarcted and normal myocardium.

Animals↗
PubMed1986

Validation of a single crystal for measurement of transmural and epicardial thickening.

Conventional measurement of wall thickening with two transit-time crystals requires considerable skill, is associated with myocardial trauma, and does not discern the function of different layers of the left ventricular (LV) wall. To overcome these limitations, we have developed a 10 MHz pulsed Doppler technique that measures thickening at any depth of the LV wall from a single crystal sutured to the epicardium. To verify its accuracy, we compared measurements of thickening fraction (TF) by pulsed Doppler and transit-time methods in 25 open-chest dogs. The epicardial Doppler crystal was placed over an intramyocardial crystal positioned either in the subendocardium or midwall. The epicardial crystal acted as both the Doppler transducer and the transit-time transmitter, so that TF was measured by each technique at the same site. A wide range of regional function (transmural TF:-28-42%, epicardial TF:-20-28%) was produced by coronary occlusion followed by reperfusion, and by isoproterenol and phenylephrine infusions. There was a good correlation between the two methods, both for transmural TF (r = 0.98, 107 paired measurements) and epicardial TF (r = 0.99, 70 paired measurements). Despite marked changes in function, the two techniques yielded similar measurements under all of the conditions tested (base line, ischemia, 5, 15, 30, 60, 120, and 180 min of reperfusion, isoproterenol and phenylephrine). One-millimeter errors in selecting the depth of the Doppler sample volume did not significantly affect the accuracy of TF measurements. Thus the single pulsed Doppler crystal provides a simple, atraumatic, and accurate means for measuring myocardial function, both transmurally and in selected layers of the LV wall.

Animals↗
PubMed1986

Efficacy and safety of moricizine in patients with ventricular tachycardia: results of a placebo-controlled prospective long-term clinical trial.

This was a prospective, placebo-controlled, single-blind trial of moricizine (ethmozine) in a dose averaging 10 mg/kg/day in 50 patients, the single entrance criterion being the presence of 10 or more runs of nonsustained ventricular tachycardia (VT) on a screening 24 hr ambulatory electrocardiographic (ECG) recording. Electrophysiologic study was not included as part of this trial design. The placebo frequency of VT (average 3 days of recording) was 1036 +/- 479 runs of VT per day. Most patients (31/50) had coronary artery disease. The study population had a mean left ventricular ejection fraction (LVEF) of 36 +/- 16%; 20 patients also had a history of sustained VT. Protocol failure was defined as failure to achieve a 75% or greater reduction in runs of VT (as judged by ambulatory ECG recording) and/or recurrence of sustained VT while on moricizine. Among the 48 patients treated with moricizine, the drug was initially efficacious in 35 (73%), with two-thirds having total abolition of nonsustained VT. Although it was effective in reducing runs of nonsustained VT, moricizine was ineffective in preventing the recurrence of sustained VT (63% failure rate). Side effects were uncommon and the drug was well tolerated in most patients with LVEFs of 30% or less.

Aged↗
PubMed1986

Surgical ablation of ventricular tachycardia: improved results with a map-directed regional approach.

To determine whether a regional approach to surgery for ventricular tachycardia would improve on the results of previously reported methods of endocardial resection, an analysis was performed of our surgical experience over a 5 year period. Of 46 consecutive patients operated on for recurrent sustained ventricular tachycardia or ventricular fibrillation, 39 patients with ischemic heart disease underwent subendocardial resection and/or cryoablation. The mean age of the patients was 61 +/- 8 (SD) years, the mean left ventricular ejection fraction was 32 +/- 11%, and the mean number of ineffective antiarrhythmic drugs was 3.8 +/- 1.2 per patient. In 35 of 39 patients in whom mapping data were obtainable, 56 (86%) tachycardias had earliest sites of activation in the left ventricle and nine (14%) had earliest sites in the right ventricle. Ten patients had 14 tachycardias (21%) mapped to areas outside visible dense scar. Of these 35 patients, 10 underwent localized subendocardial resection and 25 underwent a regional procedure in which all areas activated before the surface QRS during ventricular tachycardia were excised and/or cryoablated. In the operative survivors of electrophysiologically guided surgery, three of eight (38%) patients with the localized and one of 24 (4%) patients who underwent the regional procedure had recurrence of ventricular tachycardia during a follow-up period of 1 to 59 (mean 22 +/- 17) months (p = .04). The favorable outcome of regional surgery was not influenced by the presence of multiple morphologies in 54%, disparate sites of origin in 29%, or inferior wall foci in 46% of patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Abrupt withdrawal of beta-blockade therapy in patients with myocardial infarction: effects on infarct size, left ventricular function, and hospital course.

The effects of abrupt withdrawal or continuation of beta-blockade therapy during acute myocardial infarction were evaluated in 326 patients participating in the Multicenter Investigation of the Limitation of Infarct Size (MILIS). Thirty-nine patients previously receiving a beta-blocker and randomly selected for withdrawal of beta-blockers and placebo treatment during infarction (group 1) were compared with 272 patients previously untreated with beta-blockers who were also randomly assigned to placebo therapy (group 2). There were no significant differences between the two groups in MB creatine kinase isoenzyme (15.8 +/- 10.9 vs 18.2 +/- 14.4 g-eq/m2, respectively) estimates of infarct size, radionuclide-determined left ventricular ejection fractions within 18 hr of infarction (0.44 +/- 0.15 vs 0.47 +/- 0.16) or 10 days later (0.42 +/- 0.14 vs 0.47 +/- 0.16), creatine kinase-determined incidence of infarct extension (13% vs 6%), congestive heart failure (43% vs 37%), nonfatal ventricular fibrillation (5% vs 7%), or in-hospital mortality (13% vs 9%). Patients in group 1 had more recurrent ischemic chest pain (p = .002) within the first 24 hr after infarction, but not thereafter. However, this did not appear to be related to a rebound increase in systolic blood pressure, heart rate, or double product. In a separate analysis, 20 propranolol-eligible group 1 patients randomly selected for withdrawal of beta-blockade (group 3) were compared with 15 patients randomly selected for continuation of prior beta-blockade therapy (group 4). This comparison yielded similar results. These data indicate that the beta-blockade withdrawal phenomenon is not a major clinical problem in patients with acute myocardial infarction. beta-Blockade therapy can be discontinued abruptly during acute myocardial infarction if clinically indicated.

Aged↗