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Biomedical subjects

R H Jones

Publications and source records attributed to R H Jones.

At least 253 records · Page 14Linked to original sources

Evidence for a direct effect of bacitracin on cell-mediated insulin degradation in isolated hepatocytes.

In freshly isolated hepatocytes, in which extracellular degradation of insulin was very low, the degradation velocity was first-order with respect to the amount of insulin bound at steady state. The addition of bacitracin decreased the degradation velocity considerably, so that a higher proportion of cell-associated radioactivity remained intact. The results demonstrate that bacitracin affects the mechanism of insulin processing by intact hepatocytes.

Animals↗

Biosynthetic human insulin in the treatment of diabetes. A double-blind crossover trial in established diabetic patients.

94 diabetic patients established on treatment with porcine (n = 47) or bovine (n = 47) insulin took part in a double-blind crossover trial, in which 6-week periods of treatment with the appropriate animal insulin were compared with periods of treatment with biosynthetic human insulin (BHI). 6 patients withdrew during the trial, in 3 cases because of hypoglycaemia while taking BHI. In bovine-insulin-treated patients, the mean glucose level (mean of seven capillary-blood samples over 1 day), the modified M index, and total daily insulin requirement were the same on BHI and bovine-insulin treatment. For porcine-insulin-treated patients, mean glucose level and the modified M index were slightly higher on BHI than on porcine-insulin treatment (9.7 vs 9.0 mmol/l and 79.6 vs 65.0, respectively), despite an average increase of 2.3 units/day of BHI after 6 weeks of such treatment. Hypoglycaemic episodes were not significantly more or less frequent on BHI in either group of patients. In both groups fasting blood glucose was higher during BHI treatment than during animal-insulin treatment (14.2 vs 12.8 mmol/l [bovine group]; 12.1 vs 9.6 mmol/l [porcine group]). In bovine-insulin-treated patients blood glucose before the evening insulin injection was higher on BHI than on bovine insulin (11.6 vs 10.0 mmol/l). BHI appears to be a safe alternative to porcine or bovine insulin. Differences in the pharmacokinetics of BHI may account for the observed differences in blood-glucose responses.

Adult↗

Assessment of left ventricular function by resting and exercise radionuclide angiocardiography following acute myocardial infarction.

Left ventricular function was evaluated by first-pass radionuclide angiocardiography in 42 patients at 3 and 8 weeks following acute myocardial infarction. Left ventricular ejection fraction, diastolic volume, and wall motion were measured at rest and submaximal exercise at 3 weeks and at rest, submaximal and maximal exercise at 8 weeks. The mean ejection fraction, end-diastolic volume, and wall motion index did not change between 3 and 8 weeks in any group either at rest or during submaximal exercise. Ventricular function was decreased at rest in patients with previous and anterior myocardial infarctions, but not in patients with inferior and subendocardial myocardial infarctions. During maximal exercise at 8 weeks, nine patients (21%) had ST segment depression, whereas 25 patients (60%) had a decrease in ejection fraction or a deterioration in wall motion. These abnormalities of ventricular function during exercise occurred equally among the infarct groups. Radionuclide angiography in patients with recent myocardial infarction demonstrated highly variable ventricular function at rest and/or during exercise in each infarct subgroup.

Adult↗

Cardiac response to exercise in patients with chronic aortic regurgitation.

Rest and exercise measurements of left ventricular (LV) ejection fraction (EF) and volumes were obtained by radionuclide angiocardiography (RNV) in 30 patients with severe aortic regurgitation (AR). The ratio of peak systolic pressure to end-systolic volume was used as an index of contractility. Volumetric cardiac output (CO) averaged 11.7 +/- 3.8 L/min at rest and 18.4 +/- 5.6 L/min during exercise. Much individual variation occurred in LVEF and end-diastolic volume (EDV) responses to exercise, and there was no consistent change in these measurements. Resting hemodynamic parameters and clinical history correlated poorly with changes observed during exercise. An increase in heart rate was one mechanism used by all 30 patients to increase CO during exercise. An inverse relationship was defined between the change in myocardial contractility and the change in EDV during exercise. Patients with the greatest increase in contractility during exercise showed the greatest decrease in EDV. Less use of an exercise increase in contractility was associated with an exercise increase in EDV to meet the demand for greater CO. Therefore, exercise measurements of LV function provide unique information regarding the degree of impairment of the LV myocardium in these patients with chronic AR.

Adolescent↗

Prospective evaluation of radionuclide angiocardiography for the diagnosis of coronary artery disease.

This investigation assesses prospectively the accuracy of rest and exercise radionuclide angiocardiography (RNA) in detecting coronary artery disease (CAD). By retrospective analysis of 496 patients, optimal RNA criteria were determined for the presence or absence of CAD. Multivariate analysis of patients with normal coronary arteries on catheterization provided a formula to predict normal exercise ejection fraction (EF) in a given patient. The presence of CAD was indicated by 1 or more of the following RNA measurements: (1) rest EF less than 0.50, (2) exercise EF at least 0.06 less than the predicted value, (3) exercise increase in end-systolic volume greater than 20 ml, (4) exercise-induced wall motion abnormality. The absence of CAD was indicated by the absence of all 4 criteria. After applying these criteria to 221 consecutive patients, the RNA determinations were compared with the catheterization, determinations. Significant CAD was present in 71% of the patients studied. The sensitivity of the test was 0.87 and the specificity 0.54. Thus, because of its high sensitivity, RNA is of value in screening patients under consideration for cardiac catheterization. No patient with significant left main coronary narrowing and only 4 of 65 patients with 3-vessel disease were misdiagnosed. The poor specificity of the test, however, limits its overall accuracy.

Adult↗

The use of ventilation and perfusion lung scans to document changes following experimental pulmonary embolism.

Ventilation and perfusion lung scans were used to further document haemodynamic and respiratory changes following experimental pulmonary embolism. Changes in alveolar ventilation were only slightly greater in embolised areas of lung compared to unembolised areas, and neither heparin nor isoprenaline made any appreciable difference to ventilation. Perfusion scans revealed that large amounts of blood can flow around a massive pulmonary embolus and most of the increase in pulmonary blood flow following isoprenaline occurred in the non-embolised areas of the lung.

Animals↗

The influence of heparin and isoprenaline on the changes produced by pulmonary embolism.

The haemodynamic and respiratory changes occurring acutely after pulmonary embolism induced in dogs were documented, and the effect of heparin and isoprenaline on the emboli and on the changes induced were also studied. Heparin led to a greater reduction in embolus weight compared to control animals, but in the short time interval of this study it did not lead to improvement, in the respiratory or haemodynamic parameters. Isoprenaline led to increased pulmonary artery flow and a reversal of changes in lung compliance. It is concluded that both these agents should be instituted as soon as possible following pulmonary embolism.

Animals↗

Effects of exercise training on ventricular function in patients with recent myocardial infarction.

We evaluated the effects of 6 months of exercise training (bicycle ergometry, walking and jogging) on exercise performance and ventricular function in patients with recent myocardial infarction. Fifteen patients were selected on the basis of myocardial infarction at least 6 weeks but not more than 6 months before the study and age younger than 65 years. The patients were evaluated by maximal treadmill exercise testing and radionuclide angiography at rest and exercise before and after training. Before exercise training, maximal treadmill exercise time ranged from 1.5 to 11 minutes, ejection fraction at rest from 18% and 67% and end-diastolic volume from 108 to 208 ml. The mean EF was 48 +/- 5% (+/- SD) at rest and did not change at maximal exercise (48.5 +/- 5%). All 11 patients who completed the exercise training program achieved a significant training effect, as defined by a reduction in heart rate at 50% maximal pretraining effort or an increase in maximal treadmill time. The mean ejection fraction and end-diastolic volume and wall motion abnormalities at rest and at comparable pretraining exercise work loads and heart rates were not significantly different after training. Despite a wide range of rest and exercise ventricular function, patients with recent uncomplicated myocardial infarcts significantly increased their exercise performance. Because rest and exercise ventricular function were comparable before and after training, improvement in exercise performance probably resulted from training effects on the peripheral vasculature.

Adult↗

Ejection fraction response to exercise in patients with chest pain, coronary artery disease and normal resting ventricular function.

We studied the ejection fraction (EF) response to upright exercise using first-pass radionuclide angiography (RNA) in 281 patients with chest pain, significant coronary artery disease and normal resting ventricular function. A wide range of resting function (heart rate and EF) and exercise function (heart rate, EF and peak work load) was measured in this population. The EF response to exercise (delta EF) varied widely, ranging from a decrease of 36% to an increase of 26%. Twenty-eight clinical, catheterization and RNA variables were examined to determine their relationship to delta EF. Considered individually, the variables showing the strongest relationship were resting pulse pressure, positive exercise ECG changes and adequate exercise. Multivariable analysis identified resting pulse pressure, adequate exercise, resting EF, the change in end-diastolic volume index with exercise, positive exercise ECG changes and, to a lesser degree, the number of diseased vessels as variables that were significant independent predictors of delta EF. These observations indicate that delta EF is a complex response that is influenced by many pathophysiologic variables in the presence of coronary artery disease. Several of these variables are not related to the extent of coronary artery disease.

Adult↗

Acute medicine in a general practitioner hospital.

Admissions during 1980 to a hospital staffed by general practitioners are analysed. Almost all (94 per cent) were acute admissions. The mean length of stay was 11.7 days and the mean age of the patients 63.3 years, with 40 per cent of them under 65 years of age. Two thirds of the patients were discharged to their homes and only 7 per cent of patients spent more than four weeks in hospital. General practitioner hospitals have medical, social and economic advantages over large district hospitals for certain acutely ill patients and have an important role in primary medical care.

Acute Disease↗

Mechanism of action of insulin and insulin analogues. A comparison of the hepatic and peripheral effects on glucose turnover of insulin, proinsulin and three insulin analogues modified at positions A1 and B29.

A [14C]-glucose tracer infusion method was used to compare the effects of insulin infusion on glucose metabolism with the effects of infusion of three semisynthetic modified insulins and of proinsulin. Insulin produced hypoglycaemia in the anaesthetised dog by decreasing hepatic glucose production and increasing peripheral glucose utilisation. Compensatory antihypoglycaemic mechanisms eventually modified these responses. A1, B29-Diacetyl insulin exerted an hypoglycaemic effect entirely by stimulation of peripheral glucose uptake. A1-B29 crosslinked insulins and proinsulin produced hypoglycaemia almost entirely by decreasing hepatic glucose production and had little effect on tissue uptake. These observations suggest that insulin analogues may have actions in vivo that are qualitatively different from those of native insulin and suggest that certain analogues have a predominant action on the liver. This has important therapeutic implications concerning the development of semisynthetic insulins for clinical use.

Animals↗

Cardiac function during rest and exercise in patients with mitral valve prolapse. Role of radionuclear angiocardiography.

The clinical features of mitral valve prolapse syndrome and ischemic coronary disease overlap, making differentiation of the two conditions difficult. Furthermore, many patients have both conditions. This study assessed changes in ventricular function during rest and exercise in patients with mitral valve prolapse alone and in patients with prolapse and concomitant coronary artery disease. Twelve patients with angiographically documented mitral valve prolapse and normal coronary anatomy and 11 patients with normal coronary anatomy and no mitral valve prolapse had increased ejection fraction and demonstrated no wall motion abnormality during exercise. Changes in ventricular function during exercise in 11 additional patients with mitral valve prolapse demonstrated on echocardiography were similar to those in the group with mitral valve prolapse and normal coronary anatomy seen on angiography. In contrast, 6 of 11 patients with mitral valve prolapse and coronary arterial stenosis demonstrated on angiography had a decreased ejection fraction and exhibited wall motion abnormalities during exercise. These results suggest that mitral valve prolapse alone has no detrimental effect on ventricular function during rest and exercise and that exercise-induced abnormalities in ventricular function are related to the presence and severity of coronary artery disease and not to mitral valve prolapse.

Adult↗

Radionuclide angiocardiography in the diagnosis of congenital heart disorders.

Radionuclide angiocardiography provides a noninvasive assessment of cardiac function and blood flow through the heart and lungs. During the past three years, this procedure has been used at the Duke University Medical Center for evaluation of 343 patients with congenital heart disorders. A review of this experience shows tat the resulting data were frequently useful in the surgical management of these patients. In patients with abnormal blood flow patterns, noninvasive imaging of blood flow was useful before and after operative correction. Radionuclide measurements of left-to-right intracardiac shunts were sufficiently accurate for use in the initial evaluation of patients with murmurs and to document the absence of shunt after operative closure of intracardiac septal defects. Moreover, measurements of right-to-left cardiac shunts were of benefit in the management of children with cyanotic heart disease. Measurements of left ventricular function obtained during rest and exercise were most useful in patients with origin of the left coronary artery from the pulmonary artery and in patients with congenital valvular insufficiency. This experience demonstrates that radionuclide angiocardiography provides important measurements of central hemodynamics and cardiac function which are useful in the management of patients with congenital heart disorders.

Adolescent↗

Influence of resting left ventricular function on the left ventricular response to exercise in patients with coronary artery disease.

First-pass radionuclide angiocardiography was used to access the left ventricular response to submaximal exercise in 150 patients with coronary artery disease (CAD). To test the hypothesis that resting systolic left ventricular function as determined by left ventricular ejection fraction (LVEF) was a predictor of the hemodynamic response to exercise, the study group included patients with a wide range of resting LVEF (0.12-0.82). The influences of resting LVEF, resting end-diastolic volume, the number of diseased vessels, exercise end point and exercise double product on the change in LVEF (delta LVEF) during exercise were tested using multiple linear regression analyses. Resting LVEF was a highly significant predictor of the delta LVEF (p = 0.0001). Exercise duration was not related to either the resting LVEF or the delta LVEF. For the 112 patients in whom coronary anatomy was known, resting LVEF retained its significance as a predictor of delta LVEF (p = 0.002) even after adjustment for the significance of the extent of CAD (p = 0.0007) and the exercise end point (p = 0.06). Patients with normal resting LVEF showed the most profound decreases in LVEF, the highest frequency of new regional dysfunction and the largest relative increase in end-diastolic volume during exercise. As rest LVEF decreased, the magnitude of the delta LVEF and the frequency of new regional dysfunction decreased. Therefore, left ventricular function at rest is an important determinant of the direction and magnitude of change in left ventricular function during exercise.

Adult↗

Radionuclide quantitation of right-to-left intracardiac shunts in children.

A simple, noninvasive method for measurement of right-to-left intracardiac shunts would enhance the management of patients with congenital heart disease. This study describes application of data processing techniques used previously in dye-indicator curves to data recorded during the initial transit of radioactive bolus through the central circulation. Radionuclide angiocardiograms were performed in 20 children, mean age 30 months, immediately after cardiac catheterization for congenital heart disease. The radionuclide data recorded over the carotid artery were used to replace arterial sampling required for dye indicators, and forward triangles were fitted to calculate the right-to-left shunt in an approach similar to that of Wood for indicator-dilution curves. Ten of the children had right-to-left shunts by Fick and radionuclide measurement, and 10 of the children with septal defects had no right-to-left shunt by either technique. Both the radionuclide and Fick measurements correlated well (r = 0.95). Therefore, radionuclide angiocardiographic data may be used for accurate calculation of right-to-left shunts in small children, eliminating the need for arterial sampling.

Cardiac Catheterization↗