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Biomedical subjects

R Roberts

Publications and source records attributed to R Roberts.

At least 523 records · Page 29Linked to original sources

Comparison of bronchial responses to prostaglandin F2 alpha and methacholine.

We examined bronchial responsiveness to prostaglandin (PG) F2 alpha to determine its applicability in clinical practice and to compare it with bronchial responsiveness to the pharmacologically dissimilar agent, methacholine. Inhalation tests with two fold increasing concentrations of the two agents were carried out in 19 asthmatic and four normal subjects. The results were expressed as the provocation concentration causing a 20% fall in forced expiratory volume in 1 sec (PC20). The range of concentrations required to determine the PC20 was greater with PGF2 alpha (0.0001 to less than 5 mg/ml) than that with methacholine (0.07 to 30.96 mg/ml). Side effects of cough, retrosternal irritation, and expectoration of sputum were more frequent after PGF2 alpha. Repeat measurements in the same subjects showed that response to PGF2 alpha were as highly reproducible (r = 0.98, p less than 0.001) as previously reported with methacholine, and there was a cumulative dose effect (p less than 0.001). PC20PGF2 alpha correlated with PC20 methacholine (r = 0.5, p less than 0.01), but to a lesser degree than was previously demonstrated between histamine and methacholine. The poorer correlation was explained by the results of four subjects tolerant to PGF2 alpha relative to methacholine, three of whom were aspirin (ASA) intolerant; the correlation was much stronger when these subjects were excluded from analysis (r = 0.91, p less than 0.001). The results suggests that (1) PGF2 alpha is not a suitable agent to use in clinical practice to measure nonspecific bronchial responsiveness because of the wide dose range and unpleasant side effects, (2) the bronchial responsiveness of different individuals to PGF2 alpha and methacholine is usually well correlated and is thus unrelated to specific receptor activity, and (3) there is a relative reduction in responsiveness to PGF2 alpha in some asthmatics, particularly those with ASA intolerance.

Adult↗

Laboratory and initial clinical studies of nifedipine, a calcium antagonist for improved myocardial preservation.

This report summarizes five years of laboratory investigations and the initial six-month clinical experience with a calcium antagonist, nifedipine, added to a cold hyperkalemic cardioplegic solution for enhancement of myocardial protection. Regional ischemia was created in 112 dogs and global ischemia in 98 dogs, under normothermic and two hyperthermic states. Control solutions, two clinical cardioplegic solutions, and nifedipine solutions were compared. Infusion of nifedipine during regional ischemia and reperfusion intervals resulted in a two-to-threefold reduction in injury volume and maintenance of normal left ventricular function in contrast infusion of nitroprusside. Nifedipine solutions (0.2 microgram/ml) provided superior preservation of left ventricular function in comparison to the two cardioplegic solutions after one hour of global ischemia at 37 degrees C and two hours at 18 C. In a clinical trial of nifedipine in cold potassium cardioplegia, 38 high risk patients with poor ventricular function have been treated; 22 of which were intensively studied serially with radionuclide ventriculography and pyrophosphate scans, myocardial isoenzyme determinations, 24 hour EKG recordings and intra- and postoperative hemodynamic studies. Of the 35 patients admitted to the intensive care unit (ICU), 33 have survived. Stroke work and cardiac indices return promptly to near normal levels after operation. The time-isoenzyme activity curves are low and radionuclide determined ejection fractions show no change for the study group. Death from acute postischemic cardiac failure did not occur in treated patients and the usage of intra-aortic balloon pump (IABP) has decreased threefold in comparison with 40 similar high risk patients treated concurrently with cardioplegic solution alone. It is concluded that nifedipine is a potent adjunct to cold hyperkalemic cardioplegic solution in high risk patients.

Adult↗

A new scintigraphic technique for assessment of right atrial function.

Gated radionuclide imaging with 99mTc-labeled red blood cells was employed to assess changes in right atrial (RA) volume in 17 subjects. Studies were repeated within two hours in five of 12 normal subjects and at two and ten days after infarction in five patients. Time-activity curves were generated for the RA and right ventricle (RV) from variable regions of interest defined by automatic edge detection. The RA time-activity curve exhibited four phases: filling, early emptying, equilibration, and late emptying. Repeated measurements of RA early emptying rates correlated closely in normals (r = 0.93). Early RA emptying and RV filling rates corresponded closely (r = 0.89). In four patients with infarction, the RA emptying rate was slowed on the first study but had normalized by 10 days. In a patient with inferior infarction and suspected RV infarction, the RA emptying rate was depressed and remained so for 10 days. Thus, relative changes in right atrial volume can be assessed reproducibly by a radionuclide technique, which is relatively independent of geometric assumptions. This technique offers great promise as a method to assess atrial function in health and disease.

Adult↗

Pseudodiphtheria: prominent pharyngeal membrane associated with fatal paraquat ingestion.

Three patients presented with prominent pharyngeal membranes suggestive of tonsillar-pharyngeal diphtheria, but later found to be caused by oral ingestion of the herbicide paraquat. In all cases appropriate therapy was delayed because of failure to include paraquat in the differential diagnosis: Paraquat ingestion should be considered in all patients with prominent tongue and pharyngeal membranes.

Adult↗

Nifedipine and acute myocardial infarction.

In consideration of the results of experimental studies indicating that nifedipine, a vasodilating calcium antagonist with little inotropic or electrophysiological effects, increases coronary flow to both normal and ischemic zones potentially rendering protection of ischemic myocardium as well as the results of clinical studies in patients with angina pectoris, this pilot study was carried out in patients with acute myocardial infarction to evaluate the clinical, hemodynamic and electrophysiological responses. Nifedipine was administered sublingually in a dosage of 10 mg initially, after an interval of 1 to 1.5 hours and thereafter to maintain the pressure at the level prevailing after three hours. As compared with a control group, the frequency of ventricular dysrhythmia as well as the frequency of complex dysrhythmias in the 17 treated patients were similar (mean 313 vs. 325 PVCs/24 hours; and 5.9 vs. 3.6 episodes respectively in treated and controls). No patient developed evidence of second or third degree AV block. Systemic vascular resistance fell from 1661 to 1283 dyne . s . cm-5 and cardiac index increased from 3.2 to 3.59 l/min/m2 at one hour. Arterial pressure decreased from 146/93 to 131/88 mm Hg. Pulmonary artery pressure remained unchanged in five patients and decreased by more than 3 mm Hg in four. Thus, in patients with acute myocardial infarction nifedipine decreases systemic resistance and, provided preload is not substantially reduced, increases cardiac output. Neither an exacerbation of chest pain nor an increase in ventricular dysrhythmia was observed. Extensive clinical investigation will be needed to definitively characterize effects of nifedipine on infarct size, coronary flow and prognosis of patients with acute myocardial infarction.

Acute Disease↗

The effect of hyperbaric oxygen on infarct size in the conscious animal.

The effect of hyperbaric oxygen (HBO) on infarct size associated with myocardial infarction remains uncertain. Accordingly, the present study was performed in 46 conscious dogs with experimental infarction to determine the effect of HBO on enzymatic estimates of infarct size. Since HBO may affect plasma creatine kinase (CK) release or disappearance, parameters used to calculate enzymatic estimates of infarct size from plasma CK, we assessed infarct size by directly measuring myocardial CK depletion. Twenty-three animals were given HBO (2 atm of pressure) for 3 h immediately after coronary occlusion and results of infarct size compared to those in 23 dogs with occlusion who remained in room air. In 10 other animals CK release was measured after coronary occlusion in 5 controls and compared to 5 treated. In 5 normal animals the CK disappearance rate of purified canine CK was determined before and after HBO. Infarct size was determined 24 h after coronary occlusion and in the treated animals averaged 25.4 +/- 1.3% of LV (mean +/- SEM), and being similar to controls (26.7 +/- 1.4, P greater than 0.25). The plasma CK disappearance rate before and after HBO was the same being 0.0072 +/- 0.0022 (min-1) and 0.0073 +/- 0.0021, respectively. Total CK released into the plasma was also the same in treated and controls (2232 +/- 210 IU and 2011 +/- 232), as was the ratio of CK released to that depleted from the myocardium (0.15 +/- 2% vs 0.15 +/- 3%). Our results indicate: (1) HBO does not reduce infarct size produced experimentally in the conscious dog; (2) HBO does not affect CK release or disappearance; and (3) estimates of infarct size by plasma CK remain valid despite administration of HBO.

Animals↗

Improved radioimmunoassay for creatine kinase isoenzymes in plasma.

We describe convenient and relatively rapid procedures for purifying creatine kinase isoenzymes MM, BB, and MB, and their use in an improved radioimmunoassay for creatine kinase isoenzymes in plasma. The modifications include use of: (a) BB with a specific activity of 400 kU/g, which can be labeled with a specific radioactivity of 20 Ci/g; (b) albumin-free purified MB as inhibitor; (c) antiserum to MB creatine kinase; and (d) a second-antibody technique that necessitates only a 15-min incubation. The radioimmunoassay for MB has a sensitivity of 0.2 microgram/L (80 mU/L) and a CV of less than 5%. Plasma MB average 22 (SD 12) microgram/L in 200 normal subjects; 24 (SD 12) microgram/L in 200 patients with chest pain without infarction; and 23 (SD 7) microgram/L in 43 patients with renal disease, whether measured before or after dialysis. Peak values for plasma MB averaged 191 (SD 86) microgram/L in 325 patients with documented myocardial infarction; BB was negligible. Extensive clinical experience indicates the radioimmunoassay to be suitably rapid, highly sensitive, and reliable as a diagnostic assay for MB in plasma.

Brain↗

A comparison of digoxin and dobutamine in patients with acute infarction and cardiac failure.

The hemodynamic effects of dobutamine were compared with those of digoxin in six patients with cardiac failure within 24 hours of onset of acute myocardial infarction. Dobutamine (8.5 microgram per kilogram of body weight per minute) was given intravenously for 30 minutes and then discontinued until hemodynamics returned toward base line. Digoxin (12.5 microgram per kilogram) was then given intravenously, and hemodynamics were recorded for 90 minutes. Dobutamine decreased left ventricular filling pressure (from 22.3 to 9.8 mm Hg, P < 0.02) and systemic vascular resistance (1686 +/- 188 to 1259 +/- 108 dynes . sec . cm-5), and increased cardiac index (from 2.4 to 3.2 liters per minute per square meter of body-surface area, P < 0.005) and stroke work index (from 24.6 to 36.6 g . m per square meter, P < 0.02), without changing heart rate or arterial pressure. In contrast, digoxin had no effect on filling pressure (18.3 versus 17.0) and only a slight effect on cardiac index (2.2 versus 2.4, P < 0.05) and stroke work index (21.9 versus 27.6, P < 0.05). Thus, dobutamine markedly increased cardiac output, decreased filling pressure, and relieved pulmonary congestion. Digoxin, did not affect preload or afterload.

Aged↗

Purification of canine myocardial mitochondrial creatine kinase.

Mitochondrial creatine kinase, purified for the first time, is a dimeric molecule with a mol. wt of 82,000 and does not hybridize with M or B subunits or react to their specific antiserum. A specific antiserum to the mitochondrial form was developed which does not cross-react with the B or M subunits. Thus, the mitochondrial form is biochemically and immunologically unique.

Animals↗

Purification of mitochondrial creatine kinase. Biochemical and immunological characterization.

Mitochondrial creatine kinase was purified from canine myocardium. The preparation exhibited a positively charged isoenzyme free of other creatine kinase isoenzymes and on sodium dodecyl sulfate gel exhibited a single protein band. Amino acid composition showed mitochondrial creatine kinase to be different from that of MM or BB creatine kinase and did not hybridize with the M or B subunits of the cytosolic forms. Antiserum was developed to mitochondrial creatine kinase which did not cross-react with cytosolic creatine kinases. Antiserum to cytosolic creatine kinase exhibited no reaction to mitochondrial creatine kinase. Utilizing the specific antiserum, a radioimmunoassay was developed for the specific detection of mitochondrial creatine kinase. Thus, mitochondrial creatine kinase was purified and shown to be comprised of a unique subunit which is biochemically and immunologically distinct from the cytosolic creatine kinases.

Amino Acids↗

The relevance to family physicians of core content review: evaluation of a program of continuing education.

The Core Content Review of Family Medicine was assessed for its relevance to family practice. Three sets of questionnaires were completed and assessed by 48 experienced, certificated family physicians, of whom half were faculty members from university departments of family medicine and half were in private practice. The answers to 57% of the questions were correct. In the opinion of the panelists the answers to 62% of the questions permitted discrimination between physicians providing care of good quality and those providing care that was less than adequate. The panelists rated 78% of the questions as being educationally useful. Two thirds of the questions were deemed relevant according to a composite criterion. Examples are given of the questions considered most relevant and of those considered least relevant.

Canada↗