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Biomedical subjects

E Wickham

Publications and source records attributed to E Wickham.

11 recordsLinked to original sources

Prediction of valve-related complications for artificial heart valves using adaptive neural networks: a preliminary study.

A novel approach to the prediction of valve-related complications in patients with implanted artificial heart valves is discussed. Adaptive artificial neural networks were used to identify patients at high risk of valve-related events based on preoperative data. Data from a clinical trial on 789 subjects with Carpentier-Edwards pericardial bioprostheses were used. Patients' records were divided into two groups, one of which was used for training the neural network and the other for testing the trained network and determining error rates. Patient information such as age, sex, NYHA class and anticoagulation therapy, as well as valve information such as size and the date of implant, were used as the network inputs. The neural net had a single output variable indicating the risk that an individual patient would develop a valve-related complication resulting in death. The results show that a trained neural network was able to predict valve-related deaths in the specified time interval of 1981-1991 with a high degree of accuracy. The neural network was also successful in classifying patients into high and low risk categories.

Animals↗

The lipid, lipoprotein, and apolipoprotein effects of hydroxychloroquine in patients with systemic lupus erythematosus.

Lipid, lipoprotein, and apolipoprotein effects of hydroxychloroquine were studied in 18 female patients with systemic lupus erythematosus (SLE) with mild or inactive disease. Patients were case matched (200-400 mg hydroxychloroquine daily vs no hydroxychloroquine) on several factors including daily corticosteroid dose in this cross sectional study. All had normal menstrual cycles; none smoked, used alcohol, were taking lipid altering medications or had other concurrent diseases. Patients taking hydroxychloroquine had 35-54% lower total triglyceride, VLDL-triglyceride, LDL-triglyceride, HDL-triglyceride, VLDL-cholesterol, and apolipoprotein CIII levels (p < 0.03). These results are encouraging in that hydroxychloroquine, in addition to being useful for alleviating the primary symptoms of SLE, may also be useful for ameliorating the adverse effects of corticosteroid therapy on triglyceride-rich lipoprotein metabolism.

Adult↗

The Carpentier-Edwards pericardial aortic valve: intermediate results.

The Edwards pericardial aortic valve has unique design features that minimize cusp stress and reduce abrasion wear. Wear tests and in vivo fluid dynamic tests have shown superior performance compared with other bioprostheses. Between August 1981 and July 1985, 719 isolated aortic valves were implanted in 10 US centers. Patients were aged 18 to 90 years (mean, 64 years). Men were 63.3% of the patients. Aortic stenosis was present preoperatively in 63.4% of patients. New York Heart Association functional classes III and IV were assigned to 62% of the patients. Valve sizes were 21 mm or less in 49% of patients. Concomitant procedures (most often coronary artery bypass grafting) were performed in 48% of patients. Hospital mortality was 4.7%. There was one valve-related death due to anticoagulant hemorrhage. Late mortality yielded 23 valve-related deaths: endocarditis (13), anticoagulant hemorrhage (4), thromboembolism (3), structural (2), and pannus overgrowth (1). Freedom from valve-related death at 7 years was 95.5%. Regarding valve survival, cusp tears were not seen. There were 11 calcified valves and eight explants (57 to 107 months). Seven-year freedom from all valve reoperation was 95.5%, with 11% of the patients receiving warfarin sodium, freedom of the total series from hemorrhage at 7 years was 93.3%, and from major thromboembolism, 95.8%. Echocardiographic follow-up of hemodynamics at 7 years yielded the following calculated effective orifice areas: 19 mm, 1 cm2; 21 mm, 1.3 cm2; and 23 mm, 1.4 cm2. Average mean gradient for 19-mm valves was 15 mm Hg. New York Heart Association class improved in 78% of the patients. The Carpentier-Edwards pericardial valve, carefully studied by the Food and Drug Administration guidelines, is easy to use and has excellent hemodynamics.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Relationship of arterial wall uptake of radiolabeled liposomes to the presence of monocyte/macrophage cells in the hypertensive and atherosclerotic arterial wall.

In vivo radiolabeled liposome uptake in 5 sham-operated, 7 coarctation-induced hypertensive, and 8 atherosclerotic arterial walls from New Zealand White rabbits was compared to determine the mechanism of arterial wall uptake of liposomes. Uptake between the three groups was significantly different (P less than 0.001) with a 3-fold difference in uptake between the sham-operated and hypertensive groups and the hypertensive and atherosclerotic groups. Liposome uptake was significantly higher in the atherosclerotic group of animals (P less than 0.05). Avidin-biotin immunoperoxidase staining for monocyte/macrophage cells revealed that liposome uptake increased concomitantly with arterial wall monocyte/macrophage cellular invasion and that liposome localization, determined by autoradiography, paralleled the monocyte/macrophage cellular distribution in both hypertensive and atherosclerotic arterial walls. This study provides the first direct evidence that liposomes can escape from the circulation and enter the diseased arterial wall. Furthermore, it suggests that one possible mechanism of arterial wall uptake of liposomes is via the monocyte/macrophage cell which avidly and preferentially engulfs liposomes and then passively carries them into the arterial wall during hypertensive and atherosclerotic lesion development. Liposomes could potentially be used to carry agents into the arterial wall in the study of arterial wall lesion development.

Animals↗

Prediction of angiographic change in native human coronary arteries and aortocoronary bypass grafts. Lipid and nonlipid factors.

A within-group risk factor analysis was conducted to predict angiographic change in the Cholesterol Lowering Atherosclerosis Study, a randomized, placebo-controlled trial of colestipol plus niacin therapy in men with previous coronary bypass surgery. Global angiographic change, including both native coronary arteries and bypass grafts after 2 treatment years, was the end point. Risk factors included on-trial clinical measures, plasma lipids, lipoproteins, and apolipoproteins. Univariate analysis indicated that risk factors previously observed by others in epidemiologic investigation of ischemic heart disease--total cholesterol, LDL cholesterol, non-HDL cholesterol, triglycerides, apolipoprotein B, and diastolic blood pressure--had significant effects in the placebo-treated group. Univariate analysis indicated significant effects of apolipoprotein C-III in drug- and placebo-treated groups. Multivariate analysis indicated the predominant risk factor predicting the probability of global coronary progression was non-HDL cholesterol in placebo-treated subjects and the content of apolipoprotein C-III in high density lipoproteins of drug-treated subjects. Both drug- and placebo-treated group findings point to an important role for triglyceride-rich lipoproteins in progression and regression of human atherosclerosis.

Apolipoprotein C-III↗

In vivo hypertensive arterial wall uptake of radiolabeled liposomes.

Using five sham-operated and seven aortic coarctation-induced hypertensive New Zealand White rabbits intravenously injected with neutral small unilamellar vesicles loaded with [111In]nitrilotriacetic acid, we demonstrated in vivo that the normal aortic arterial wall participates in liposome uptake and that this uptake is increased in the hypertensive aortic wall by approximately threefold (p less than or equal to 0.0001). Among the three regions examined, aortic arch, thoracic aorta, and lower abdominal aorta, the difference in uptake between the normotensive and hypertensive arterial walls was significantly different, p less than or equal to 0.05, p less than or equal to 0.0001, and p less than 0.05, respectively. The uptake by the different regions of the hypertensive arterial wall is consistent with the pathological changes present in these areas. Furthermore, the extent of liposome uptake by the aortic wall is strongly correlated with the height of the blood pressure (r = 0.85, p = 0.001, n = 11). We conclude that neutral small unilamellar liposomes can be used to carry agents into the arterial wall in vivo in the study of hypertensive vascular disease and could be especially useful for the delivery of pharmacologically or biologically active agents that would otherwise be inactivated within the circulation or are impermeable to the arterial wall.

Animals↗

Evaluation of human panelists in assessing coronary atherosclerosis.

The Cholesterol Lowering Atherosclerosis Study, a randomized, angiographic clinical trial, has demonstrated the beneficial effect of niacin/colestipol therapy on coronary and femoral atherosclerosis. The primary outcome was a panel-determined consensus score evaluating global coronary changes determined angiographically at 2 years. This article presents an evaluation of interreader agreement in independently assessing the status of native coronary arteries and overall coronary condition. Parameters include 1) identification of the presence of lesions and lesion changes; 2) estimation of lesion severity (percent stenosis) and amount of change in lesion severity; and 3) global assessment of change in coronary status. Readers independently agreed on 1) presence of lesions (82%) and change in lesions (51%); 2) percent stenosis +/- 10% (76%) and change in stenosis +/- 10% (81%); and 3) global assessment of change in coronary status within one step (96%). Results of these analyses may be useful in effectively designing angiographic trials that use a panel of human evaluators as well as computerized methods for angiographic interpretation.

Adult↗

Quantitative ultrasound pulsation study in human carotid artery disease.

Pulsation in the human carotid artery during two complete cardiac cycles was studied by using computer digitized video-frames from B-mode ultrasound images. Eight patients with identifiable atherosclerotic lesions in the common carotid immediately proximal to the bulb area were studied. Diameter, strain, and elastic modulus were compared between lesion site and an adjacent reference segment 1 or 2 cm proximal to the bulb. As controls, nine patients without identifiable lesions were analyzed. The results indicate a significantly wider diameter (p less than 0.01) at the proximal reference site in patients with lesions as compared to comparable segments in control patients. The strain was significantly lower (p less than 0.05), whereas the elastic modulus was significantly higher (p less than 0.05), at the lesion site as compared to the proximal reference sites in patients with lesions. These results may indicate that an initial dilation of the carotid artery followed by loss of wall flexibility may be associated with atherosclerotic lesion formation.

Blood Flow Velocity↗

Evaluation of epoxy ether fixed bovine arterial grafts for mutagenic potential.

Two epoxy ether compounds [glycerol polyglycidyl ether (Denacol EX-313) and ethylene glycol diglycidyl ether (Denacol EX-810)] are under consideration as alternatives to glutaraldehyde for use in the processing of an arterial graft. The two are utilized as cross-linking and sterilant agents, respectively. Epoxy resins are multifunctional alkylating agents, and bifunctional alkylating epoxide solutions are known to be mutagenic. The correlation between mutagenic potential and carcinogenicity, in addition to evidence that diepoxides are carcinogenic in mice and rats, prompted the evaluation of the mutagenic potential of the epoxy treated, clinically rinsed graft. Ames and sister chromatid exchange (SCE) test procedures were used to assess mutagenic potential. Normal saline and distilled water were selected as the most physiologically representative and procedurally acceptable extraction mediums for the Ames and SCE tests, respectively. The results of the Ames and SCE tests in both the activated and non activated systems indicated that there were no statistically significant differences detected between various test article concentrates and the spontaneous mutation controls for both the activated and non activated systems. The epoxy treated graft was determined to be non mutagenic and demonstrated no dose related responses by these methods.

Animals↗