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Biomedical subjects

R Roberts

Publications and source records attributed to R Roberts.

At least 487 records · Page 27Linked to original sources
PubMed1983

Chronic beta blockade therapy in patients after myocardial infarction.

This report is a review of greater than 18 years of experience with clinical trials that have examined the effect of beta blockers on mortality after acute myocardial infarction (MI). Despite inadequate sample size, a substantial number of the early randomized trials demonstrated a trend toward reduction in mortality after MI using a number of beta blockers. This review highlights the larger prospective randomized trials, especially the Multicenter International Trial of practolol, the Norwegian Multicenter Study of timolol and the Beta-Blocker Heart Attack Trial (BHAT) of propranolol. The combined strength of these long-term trials, comprising greater than 8,000 patients, demonstrates a consistent and statistically significant reduction in mortality after MI. Both the Norwegian timolol study and BHAT further document a substantial reduction in mortality in patients stratified according to risk groups, with a reduction in mortality after complicated or uncomplicated first MI or in patients with prior MI. These 2 studies also document a reduction in sudden death mortality in the first year after MI. Data regarding subendocardial MI is more variable, but the Norwegian timolol study documents a substantial reduction in mortality after subendocardial MI. Based on this review, we recommend treatment of all patients who can tolerate beta blockade after acute MI, beginning in the late hospitalization phase and continuing for at least 2 years.

Adrenergic beta-Antagonists↗
PubMed1983

Molecular heterogeneity of creatine kinase isoenzymes.

Cytoplasmic creatine kinase (ATP:creatine N-phosphotransferase, EC 2.7.3.2) is a dimeric enzyme exhibiting three isoenzymes (MM, MB and BB). The two subunits have been reported to have identical molecular weights (Mr) of 41 000. We have demonstrated that the M subunits from human, canine, rabbit, mouse and bovine tissue have similar apparent Mr values of 43 000 as determined by SDS-polyacrylamide gel electrophoresis. In contrast, the Mr of the B subunits was different from that of the M subunit and varied with each species (human Mr 44 500; canine Mr 46 000; rabbit Mr 44 000 and mouse Mr 49 000). Cyanogen bromide cleavage showed all M subunits to have identical fragments, while B subunits exhibited cleavage products with patterns unique for each species. Despite the differences in Mr and cyanogen bromide fragment patterns, all B subunits were capable of producing enzymatically active hybrid (MB) molecules in combination with M subunits from any species tested. Mitochondrial creatine kinase subunits exhibited identical molecular weights and were similar to the M subunits and failed to combine with either the cytosolic M or B subunits. Thus, B subunits appear less conserved during evolution compared to M subunits, but have retained the amino acid sequences essential for subunit interaction and enzymatic activity.

Animals↗
PubMed1983

Intravenous nitroglycerin in acute myocardial infarction.

Until recently, the use of nitroglycerin in patients with acute myocardial infarction has been contraindicated primarily because of possible hypotension or tachycardia which, with sublingual or oral preparations, would be difficult to control. The introduction of intravenous nitroglycerin and its use during experimentally induced infarction paved the way for its use in patients with acute myocardial ischemia. It was shown that nitroglycerin, administered intravenously during experimentally induced coronary artery occlusion, redistributed flow to the subendocardium of the ischemic area while it maintained flow to the normal areas and was associated with decreased S-T segment elevation. Preliminary studies in patients with acute infarction have confirmed the beneficial effect of intravenous nitroglycerin on S-T segment elevation, and a subsequent study in 31 patients with acute infarction showed a decrease in infarct size with improved hemodynamics. In a more recent randomized prospective study in 85 patients with acute myocardial infarction, we found that intravenous nitroglycerin was associated with a decrease in infarct size in patients with inferior infarction (36 percent reduction, p less than 0.05) but that it had no effect on infarct size in patients with anterior infarction. Whether or not nitroglycerin should be used routinely for reduction of infarct size remains to be determined, but results indicate that it is effective and safe for the treatment of cardiac failure in patients with acute myocardial infarction.

Blood Pressure↗
PubMed1983

Enzymatic estimation of myocardial infarct size when early creatine kinase values are not available.

Estimates of myocardial infarct (MI) size based on plasma creatine kinase (CK) are used widely for prognosis and in the assessment of therapy designed to salvage ischemic myocardium. However, if the initial plasma CK activity is elevated, MI size will be underestimated. To determine the impact of loss of early CK values on estimates of MI size and to develop a procedure to compensate for it, estimates of MI size based on complete and incomplete MB and total CK time-activity curves from 120 patients (experimental group) were compared. Estimates of MI size based on data inclusion intervals beginning at 24, 12, 8, and 4 hours before peak CK were 11, 14, 23, and 47% smaller than values based on complete CK curves, but the correlation was good between complete and incomplete estimates of MI size at any given interval, with r values ranging from 0.91 to 0.98. The derived correction factors were then prospectively applied to a new population (n = 25) with complete CK curves to compensate for purposely omitted early CK values. The corrected estimates of MI size were within 7% of those based on the complete CK curves. Similar results were obtained for transmural and nontransmural and anterior or inferior MI. Thus, if peak plasma CK is known, underestimation of MI size can be compensated for despite the unavailability of early CK values. Since greater than 90% of patients present before plasma CK has reached its peak (24 hours), MI size can be obtained in nearly all patients. Thus, being able to correct for unavailable early CK values makes MI size a more widely applicable endpoint for use in clinical trials and patient management.

Aged↗
PubMed1983

In vitro translation of canine mitochondrial creatine kinase messenger RNA.

The cell-free translation products of mRNA from canine myocardium were immunoprecipitated using antiserum specific for either the MM or mitochondrial creatine kinase subunit. The two subunits were shown to be encoded by the nuclear genome and translated from separate mRNAs. The mitochondrial subunit was translated as a polypeptide with a molecular weight approximately 6,000 greater than the mature form of the enzyme. In contrast, the M-subunit was translated as a polypeptide having a molecular weight identical to that of the mature cytosolic M-subunit. It is assumed that the mitochondrial subunit precursor must be proteolytically processed during translocation from the cytoplasm into mitochondria.

Animals↗
PubMed1983

Usefulness of abrin as a positive control for the human tumor clonogenic assay.

A series of approaches were tested in order to develop a simple technique for introducing a routine positive control into the Human Tumor Clonogenic Assay. Of the various techniques tested, the best proved to be the addition of the toxic plant lectin abrin to the culture system. When added to the agar underlayer of the culture system so that the final abrin concentration in culture was 10 micrograms/ml, survival of human tumor colony-forming units (TCFU) was reduced to less than 1% of control in 16/34 (47%) of human tumors, to less than 10% in 33/34 (97%) and to less than 30% in all tumors tested (100%). A clear dose-response relationship to fractional survival was observed for individual tumors tested at multiple dose levels of abrin. When the dosage of abrin was reduced to 1 micrograms/ml, survival of TCFU was reduced to less than 30% in 25/28 (89.2%) of experiments. Inclusion of abrin controls in clonogenic assays thus provides an excellent and reproducible positive control to which cytotoxic effects of a variety of therapeutic agents can be compared.

Abrin↗
PubMed1983

Estimation of infarct size with MB rather than total CK.

We estimated infarct size in 95 patients with clinically uncomplicated infarction from total CK and results were compared to infarct size index based on plasma MB CK. Among patients with relatively low infarct size index indicative of relatively small infarctions (less than or equal to 20), estimates with total CK correlated closely with those based on MB CK (r = 0.88). In contrast, among patients with larger infarcts (infarct size index greater than 20) the correlation was poor. In this group, values for infarct size index based on total CK were 67 +/- 4 (SE)% greater than those based on MB CK. In the overall population, infarct size index based on MB (14 +/- 1 (SE) CK-gram-equivalents/m2) was less than that based on total CK (21 +/- 2). These disparities appear to reflect occult release of non-cardiac CK in patients with more extensive infarction. Thus, even in patients without overt clinical complications enzymatic estimates of infarct size are more accurate when based on MB rather than total plasma CK.

Adult↗
PubMed1983

Relapse of antibiotic associated colitis: endogenous persistence of Clostridium difficile during vancomycin therapy.

This study reports 24 patients with antibiotic associated colitis due to Clostridium difficile. Fifteen patients were treated with vancomycin due to the severity of the colitis and in eight of these a clinical relapse of the colitis occurred after vancomycin therapy was stopped. Bacteriological investigations of these patients indicated that C difficile was able to persist in stool samples during vancomycin therapy in the absence of detectable cytotoxin. This was in contrast with the seven patients successfully treated with vancomycin without relapse, and those not treated with vancomycin where both stool cultures and cytotoxin assays became negative. These results suggest that patients being treated with vancomycin for antibiotic associated colitis due to C difficile should have stool cultures done during and after treatment. Persistence of the organism in the absence of detectable cytotoxin may identify those patients who relapse and lead to either recommencement of vancomycin or alternative therapeutic approaches.

Adolescent↗
PubMed1983

Reduction of infarct size in patients with inferior infarction with intravenous glyceryl trinitrate. A randomised study.

Glyceryl trinitrate was previously said to be contraindicated in patients with acute myocardial infarction. Its intravenous administration during acute infarction, however, was associated with a beneficial effect as determined by ST segment mapping. Most recently in a selected group of patients with acute infarction and abnormal haemodynamics, intravenous glyceryl trinitrate was shown to reduce infarct size estimated by enzymes. The present study was performed to verify the safety of intravenous glyceryl trinitrate in patients with infarction under conventional clinical conditions without invasive monitoring and to determine its effect on infarct size in a prospective randomised trial involving 85 patients with infarction (43 treated and 42 control). Treated patients received glyceryl trinitrate within 10 hours of the onset of symptoms (mean 6.0 hours), and the dose was titrated to preset limits for changes in heart rate and blood pressure. In patients with inferior infarction, infarct size estimated by enzymes in the treated was only 12.2 +/- 1.8 versus 19.1 +/- 3.6 CK gram equivalents per metre squared in the placebo group. A similar but statistically insignificant trend was observed for subendocardial infarction but no difference was observed for anterior infarction. Ventricular arrhythmias determined from 24 hour tapes were more frequent in treated patients though this was not statistically significant. Lignocaine requirements in treated and control (1692 +/- 250 vs 1512 +/- 232 mg/24 h) were similar, as were the requirements for morphine (11.4 +/- 1.8 vs 12.2 +/- 2.2 mg/24 h). Results indicate that intravenous glyceryl trinitrate can be administered safely during evolving infarction without invasive monitoring and reduces infarct size in patients with inferior infarction.

Adult↗
PubMed1983

Right ventricular infarction.

Right ventricular (RV) infarction, once considered rare, is now recognized as common in patients with inferior infarction. It usually involves the posterior wall of the right ventricle and seldom the anterior right ventricle. There is concomitant transmural injury to the posterior wall of the left ventricle and interventricular septum. Severe RV dysfunction may be associated with cardiogenic shock, and conventional treatment may be deleterious. Avoidance of diuretics and administration of fluids is associated with a much better prognosis. Hemodynamic monitoring is necessary and the diagnosis should be confirmed by radionuclide assessment. Exclusion of tamponade and constrictive pericarditis by echocardiography is often essential.

Heart Ventricles↗
PubMed1983

Bronchoconstriction stimulated by airway cooling. Better protection with combined inhalation of terbutaline sulphate and cromolyn sodium than with either alone.

We compared the effect of inhaled terbutaline sulphate (1,000 micrograms), cromolyn sodium (20 mg), terbutaline plus cromolyn, and placebo on the response to respiratory heat loss (RHL) in 10 asthmatics in whom terbutaline alone did not completely inhibit the response to RHL. The medications were taken double-blind in random order 20 min before voluntary isocapnic hyperventilation of subfreezing air (-14 degrees C, 0% humidity) in twofold-increasing amounts. The response was expressed as the provocative dose of RHL to cause a 10 and 20% fall in forced expiratory volume in one second (FEV1). When compared with placebo, terbutaline produced bronchodilation and inhibition of the response to RHL. The degree of bronchodilation was small (mean delta FEV1, 3.9%) and did not correlate with the degree of protection. Cromolyn produced no bronchodilation and similar inhibition. The effect of terbutaline and cromolyn together was additive. We conclude that when bronchoconstriction stimulated by airway cooling is not prevented by a beta agonist or cromolyn given individually, that it will be more effectively inhibited by the 2 drugs given in combination.

Adult↗
PubMed1983

Enzymatic estimation of infarct size during reperfusion.

Infarct size estimated enzymatically is an objective end point for assessing interventions in patients with acute myocardial infarction and correlates with acute and long-term morbidity and mortality. However, there is concern whether such estimates are reliable in the setting of reperfusion. Reperfusion during experimental infarction and clinically with streptokinase is associated with higher plasma creatine kinase (CK) levels that peak much earlier than with sustained occlusion, indicating a more rapid release rate. In this report, experimental derivation of the parameters for estimating infarct size--myocardial CK distribution and content, CK depletion, plasma CK disappearance rate and the release ratio--are presented, together with the experimental and clinical validation of these estimates. The close correlation between myocardial CK depletion and morphometric estimates of infarct size (r = .92), which provides the basis for enzymatic estimation of infarct size, remains valid during experimental reperfusion. Plasma CK activity (100-5000 IU/l) assayed before and after incubation of streptokinase (5000 U/ml for 30 minutes at 37 degrees C) showed less than 5% variation. Plasma CK disappearance (kd) in the conscious dog before and during infusion of streptokinase (20,000 U/hour) were identical. The CK release ratio has not been determined during streptokinase therapy or experimental reperfusion, but in the experimental animal during early reperfusion, infarct size was overestimated by the plasma CK method compared with histologic estimates. Despite the overestimation, enzymatic estimates still correlate closely with histologic estimates (r = .90). The presence of a close correlation despite sudden complete early restoration of flow suggests that with the appropriate experimentally determined correction factors, one can obtain reliable enzymatic estimates of infarct size to assess the efficacy of streptokinase.

Animals↗
PubMed1983

Evaluation of problems and needs of veteran lower-limb amputees in the San Francisco Bay Area during the period 1977-1980.

From 1977 through 1980, 251 veterans from the San Francisco Bay Area received permanent lower-extremity prostheses at the two local Veterans Administration hospitals. For a survey, 213 of the 251 were contacted and 179 of them (84%) responded to written or telephone questionnaires concerning their prosthetic problems and complaints and their recommendations regarding prosthetic care. Seventy-four percent of the patients were traumatic amputees and 23 percent were dysvascular amputees. Eighty-six percent of the traumatic amputees said they wore their limbs all day, compared with only 51 percent of the dysvascular group. Seventy-one percent of traumatic and 43 percent of dysvascular amputees engaged in some form of recreational activity. There was a high incidence of complaints of pain in the residual limb: 55 percent among the dysvascular group and 44 percent among the traumatic group. Half of the patients had socket problems. Fifty-four of the 178 patients received a physical examination, a prosthetic evaluation, and a gait analysis. Among this group, 59 percent of the below-knee prostheses and 78 percent of the above-knee prostheses had inadequate socket fitting. Improper shaping of socket margins was the most frequently observed deficiency. Moreover, 41 percent of below-knee and 22 percent of above-knee amputees had mechanical skin irritation or skin breakdown in the examined residual limbs. Faulty suspension and alignment in addition to improper socket fit and construction contributed to this problem. Excessive stiffness of SACH foot heel cushions was the most common prosthetic foot problem and contributed to gait abnormalities.

Activities of Daily Living↗
PubMed1982

Salbutamol: comparison of bronchodilating effect of inhaled powder and aerosol in asthmatic subjects.

In the treatment of asthma salbutamol can be administered as an aerosol with a metered-dose inhaler or as a powder with a breath-actuated device (Rotahaler). The two forms of the drug were compared in a double-blind placebo-controlled study involving 10 asthmatic adults who were known to respond to salbutamol. The bronchodilating effect of the aerosol and the powder at doses of 200 micrograms and of the powder at doses of 200 and 400 micrograms was compared, bronchodilation being measured in terms of forced expiratory volume and vital capacity. The response was far greater to salbutamol than to placebo, but there was no significant difference between the two forms of the drug or between the lower and higher doses of powder. No side effects were observed.

Adult↗