Biomedical subjects
Publications and source records attributed to M R Holland.
The simultaneous use of two guiding catheters during angioplasty has been previously described for native coronary artery bifurcation lesions. We describe a case in which a dual guiding catheter, dual guidewire technique is used for angioplasty of a native vessel lesion spanning the anastomotic site of a sequential saphenous vein graft.
Platelet-activating factor (1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine; PAF) is a phospholipid with many physiological actions. It is synthesized by endothelial cells and a variety of others in response to stimulation with receptor-mediated agonists. In endothelial cells it remains associated with the surface of the cell and serves as a signal for adhesive interactions with leukocytes. Thus, its synthesis must be precisely regulated. In previous work we have shown that PAF synthesis is regulated at the initiating step, a phospholipase A2. Here we demonstrate that the subsequent step of PAF synthesis, the acetyl-CoA:lyso-PAF acetyltransferase, is rapidly activated when cells are exposed to thrombin or other agonists. We found that the activity increased from basal values (5 nmol/mg/min) to approximately 3-fold higher within 1 min following the addition of agonists. The enzyme activity returned to basal levels within 10 min. The pattern of activation and inactivation suggested covalent modification of the enzyme. This was supported in experiments in which we showed that homogenates had stable enhanced activity and that there was no evidence for an activator or inhibitor. Pretreatment of the cells with vanadate, an inhibitor of protein phosphatases, markedly prolonged the activation state. In subsequent studies we pretreated intact cells with vanadate to block inactivation of the enzyme and then measured the accumulation of PAF in response to thrombin. We found that it was markedly augmented and prolonged. From this we conclude that the synthesis of PAF in intact cells is regulated by the activity of the acetyltransferase. We characterized requirements for activation of acetyltransferase and found that it was not dependent on the influx of intracellular calcium but that calcium entry did influence the length of time for which the enzyme was activated. The acetyltransferase in endothelial cells was shown to be a specific enzyme that did not catalyze the transfer of long chain acyl groups from acyl-CoA to lysophospholipids and demonstrated modest specificity for the acceptor lysophospholipids. These results suggest that activation of the acetyltransferase is a crucial determinant of the amount of PAF synthesized in activated endothelial cells.
To provide on-line quantification of left ventricular cavity dimensions and function by echocardiography 60 control subjects and 10 patients with cardiac dysfunction were studied. A novel, ultrasound imaging system was used which was developed to detect and track, in real time, ventricular endocardial blood boundaries based on quantitative assessment of acoustic properties of tissue. In addition, lateral gain compensation, a robust and novel image enhancement procedure, was used to provide instantaneous measurement and display of cavity areas and functional indexes on a beat-by-beat basis within regions of interest drawn around the blood pool cavity. In control subjects, short-axis end-diastolic area averaged 13.1 +/- 3.7 cm2 (SD), end-systolic area 5.9 +/- 2.7 cm2, and fractional area change 55.6 +/- 11.2%. Apical views yielded corresponding values of 23.8 +/- 4.5 cm2, 15.5 +/- 3.4 cm2 and 34.7 +/- 7.8%. Instantaneous peak rate of cavity area change approximated 50 cm2/s in systole and 60 cm2/s in diastole in each view. Serial measurements of area and functional index were reproducible over intervals of 2 to 3 weeks. Patients with dilated ventricles exhibited average apical view area values of 49.1 +/- 6.1 cm2 and 43.1 +/- 4.9 cm2 in diastole and systole with a fractional area change of 12.2 +/- 3.0%. Thus, results with on-line echocardiographic backscatter imaging-assisted automated edge detection are reproducible and capable of delineating cardiac dysfunction conveniently, promptly and serially at the bedside.
Quantitative myocardial tissue characterization is being developed to complement and expand conventional echocardiography by delineating the physical state of myocardium under diverse pathophysiologic conditions. Real-time quantitative integrated backscatter imaging has already been applied to patients with ischemic heart disease, hypertrophic cardiomyopathy, and cardiac allograft rejection in clinical investigations performed in the United States, Europe, and Japan. A recently introduced modification of imaging processing algorithms employed for characterization of tissue facilitates automatic detection of endocardial-blood interfaces and on-line quantification of ventricular size and function. Further progress and anticipated developments in quantitative ultrasonic imaging will undoubtedly augment the clinical applications of tissue characterizations based on myocardial integrated backscatter for improved diagnosis, elucidation of pathophysiology, and assessment of cardiac function.
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The annual rate at which patients defaulted from follow up at the Wolverhampton diabetic clinic between 1971 and 1981 was 4.1% overall and 3.5% in white patients. In 1982 a study was started to discover what happened to white patients, born after 1919, who defaulted from the hospital clinic. There were 162 defaulters, of whom 19 had died. Of the remaining 143 patients, 19 were attending another hospital diabetic clinic, 22 had moved out of the area, and 28 refused to participate in the study. Seventy four agreed to participate: 39 were treated with diet, 15 with oral hypoglycaemic agents, and 20 with insulin. They were matched for sex, age, treatment, and duration of diabetes with patients attending the clinic. Non-insulin dependent defaulters were significantly more overweight at diagnosis (40% v 25%; p less than 0.05) and remained more obese. They developed significantly higher diastolic blood pressure (94 v 86 mm Hg; p less than 0.02) and higher haemoglobin A1 (HbA1) concentrations (11.7% v 8.4%; p less than 0.01). They had significantly more neuropathy at reassessment (15 v 6 out of 54; p less than 0.05) and a greater incidence of new retinopathy (p less than 0.02), which correlated with their higher diastolic blood pressures (p less than 0.01) and HbA1 concentration (p less than 0.02). In defaulters who were treated with insulin only the prevalence of neuropathy was significantly different from that in controls (p less than 0.05). Defaulters received minimal medical supervision and suffered greater morbidity than regular attenders at the clinic.
An assessment was made of the degree of metabolic control achieved in diabetic patients attending mini clinics run by general practitioners compared with that in matched diabetic patients attending a hospital clinic. Patients were grouped according to whether they were being treated with diet alone, an oral hypoglycaemic, insulin once daily, or insulin twice daily. Statistical analysis showed no significant difference between patients attending mini clinics and those attending the hospital clinic in retrospective mean blood glucose, retrospective mean glycosylated haemoglobin (HbA1), or prospective HbA1 concentrations. General practitioners providing diabetic care on an organised basis can achieve a degree of glycaemic control in diabetic patients equal to that reached by a hospital clinic.
Different methods can give different results for the same analyte, and inconsistent answers may be obtained if such results are used in linear discriminant functions. This is an important factor to consider when transporting linear discriminant functions from one laboratory to another; the example of alkaline phosphatase activity and the differential diagnosis of hypercalcaemia has recently been given. This study shows that results obtained by the method recommended by the Scandinavian Committee on Enzymes for alkaline phosphatase may be used in the calculation of the discriminant functions used for the differential diagnosis of hypercalcaemia and considers other factors that may affect the discrimination. It is concluded that, with care, linear discriminant functions may be transported from one laboratory to another.
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Explore the source record for details and available documents.