Biomedical subjects

D W Crawford

Publications and source records attributed to D W Crawford.

At least 19 recordsLinked to original sources

PubMed1995

Sources of pollution and sediment contamination in Newark Bay, New Jersey.

A review of historical water quality and sediment quality data and chemical body burdens in biota reveals significant levels of a wide range of chemicals and water quality stressors throughout the Newark Bay, New Jersey estuary. The estuary, which encompasses the Passaic River, Hackensack River, Kill van Kull, and the Arthur Kill, has been heavily impacted by both industrial and urban expansion for more than 200 years. The available information was sufficient to identify the major sources of pollution and the contributions of various metals and organic chemicals to the aquatic environment. Mass loadings for several chemicals and water quality parameters were estimated for publicly owned treatment works (POTWs) and combined sewer overflows (CSOs), industrial waste discharged either directly to the estuary or through POTWs, stormwater runoff, and accidental spills of petroleum products and hazardous chemicals. The recent trend toward regionalized waste treatment systems to provide secondary levels of treatment have provided some reductions of overall contaminant mass loadings. However, CSOs remain a significant source of untreated waste in the estuary. Additionally, the magnitude of the major sources relative to the ability of the estuary to absorb and dilute the various waste streams suggests that much more must be done to reduce chemical inputs at the source.

History, 19th Century↗

PubMed1994

Historical changes in the ecological health of the Newark Bay Estuary, New Jersey.

A review of ecological conditions in the Newark Bay estuary over the past century was conducted to characterize chemical, physical, and biological indices of the health of the estuary and to evaluate the relationship of these trends with past and current urban-industrial influences within the watershed. The available data indicate that both the diversity and the abundance of aquatic species within the estuary have been substantially reduced since the late 1800s due to the intense industrialization and urbanization that occurred throughout the region. Water and sediment quality in major rivers and bays linked to the estuary have also been severely impacted. In addition, significant natural habitat has been destroyed as a result of industrial development, urban expansion, and shoreline modifications. Each of these parameters directly influences the status and condition of the ecological community, and their deterioration has likely been the cause of multiple adverse impacts on the overall health of the ecosystem. Review of more recent studies of sediment and water quality indicates that pollution control measures and the reduction or control of other environmental stressors have produced a gradual improvement in the ecosystem over the past 2 decades.

Animals↗

PubMed1992

Probucol reduces plasma and aortic wall oxysterol levels in cholesterol fed rabbits independently of its plasma cholesterol lowering effect.

To understand further the antiatherogenic mechanism of probucol, the antioxidant effect of this agent was studied on specific cholesterol oxidation products in plasma and aortic wall in equally hypercholesterolemic New Zealand white rabbits. In order to maintain equal plasma total cholesterol levels, five control rabbits (C group) received a 1% followed by a 0.5% cholesterol enriched diet, while the probucol treated rabbits (C+P group) received a graded increase in the cholesterol supplemented diet from 1% to 3%; probucol supplementation was constant at 1%. After 9 weeks of feeding, the plasma oxysterols, cholest-5-ene-3 beta,7 alpha-diol, cholest-5-ene-3 beta,7 beta-diol, 5,6 beta-epoxy-5 alpha-cholestan-3 beta-ol, 5,6 alpha-epoxy-5 alpha-cholestan-3 alpha-ol and 5 alpha-cholestane-3 beta,5,6 beta-triol significantly increased over baseline levels in both experimental groups. However, the increase in all these products in plasma was 20-60% less in the C+P group than the C group (P < 0.05). Furthermore, the C+P aortic wall cholesterol oxide concentrations were 50-90% less than the C group (P < 0.05). The oxysterol pattern of the aortic wall was similar to plasma. Additionally, the aortic wall cholesterol content in the C+P group was 50% less than the C group (P < 0.05). The plasma cholesterol levels were not significantly different at any time point during the study and the cholesterol oxide content in the diets was the same. These results are consistent with the contention that the antioxidant properties of probucol serve as the basis for its antiatherogenic effects in vivo.

Animals↗

PubMed1992

Flow measurements in a highly curved atherosclerotic coronary artery cast of man.

Flow visualization and wall pressure measurements were made in a polyurethane cast of a cadaver coronary artery with a significant "s" shaped reverse curvature. A sucrose solution was used to simulate the kinematic viscosity of blood, with flow rates in the physiologic range. Flow visualization demonstrated significant secondary flow patterns in the wall vicinity, which increased with increasing Reynolds number. Random dye dispersion was observed at a Reynolds number of about 400, but not at 200. Dye filament patterns in the transition between the first and second curved region were predominantly influenced by the second curved region at lower Reynolds numbers, and by the first curved region at higher Re. Local wall pressure measurements demonstrated a significant centrifugal effect with large radial pressure differences across the casting. Flow resistances for the casting were considerably greater than reference Poiseuille flow values, and increased further with pulsatile flow.

Blood Pressure↗

PubMed1992

Wall shear stress estimates in coronary artery constrictions.

Wall shear stress estimates from laminar boundary layer theory were found to agree fairly well with the magnitude of shear stress levels along coronary artery constrictions obtained from solutions of the Navier Stokes equations for both steady and pulsatile flow. The relatively simple method can be used for in vivo estimates of wall shear stress in constrictions by using a vessel shape function determined from a coronary angiogram, along with a knowledge of the flow rate.

Blood Flow Velocity↗

PubMed1992

Immunolocalization of native antioxidant scavenger enzymes in early hypertensive and atherosclerotic arteries. Role of oxygen free radicals.

To elucidate the role of oxygen free radicals and lipid peroxidation in the pathogenesis of early hypertension and atherosclerosis, we studied the native distribution of three primary arterial antioxidant enzymes (AEs). Specific immunohistochemical localization of superoxide dismutase (Cu-Zn SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) was examined in the arterial wall of New Zealand White rabbits: six sham-operated normotensive/normolipidemics (NT/NL), seven coarctation-induced hypertensive/normolipidemics (HT/NL), eight normotensive diet-induced hyperlipidemics (NT/HL), and six hypertensive/hyperlipidemics (HT/HL). All three AEs were confined primarily to the endothelium in NT/NL rabbit aortas. However, in HT and HL rabbits a greater proportion of the arterial wall, including the endothelium, inner media, and middle media, displayed immunolocalization of three AEs. Multiple linear-regression analysis revealed that more than 70% of the total variability in the depth of immunolocalization of arterial AEs could be explained by changes in blood pressure and/or total cholesterol. Also, levels of plasma and arterial cholesterol oxides were significantly different (p less than 0.05) in HT and HL rabbits compared with controls, with twofold increases in NT/HLs, threefold increases in HT/NLs, and fourfold increases in HT/HLs. We conclude that intense free-radical activity in the arterial wall of HT and HL animals is one possibility and that this occurs despite the presence of abundant AEs.

Animals↗

PubMed1992

Evaluation of colestipol/niacin therapy with computer-derived coronary end point measures. A comparison of different measures of treatment effect.

BACKGROUND: The Cholesterol Lowering Atherosclerosis Study has demonstrated beneficial effect of colestipol/niacin on coronary atherosclerosis using a panel-determined global coronary change score. We now report treatment group comparisons using quantitative coronary angiographic (QCA) measures from all processable segments in 85 of 162 randomly selected baseline/2-year film pairs. METHODS AND RESULTS: Treatment benefit was established for percent stenosis for either continuous or categorical analyses with regression established regardless of the per-patient scoring procedure. In addition, treatment benefit favoring regression was established in some cases for roughness and for percent involvement, a longitudinal estimate of the percent of coronary surface involved by raised lesions. Benefit on minimum diameter was directly related to whether the segment was proximal to a graft insertion and hemodynamically related to the bypass graft. QCA correlates of panel-determined progression were increases in percent stenosis and numbers of occluded lesions in native arteries and the number of progressing lesions in bypass grafts. CONCLUSIONS: These results demonstrate that a variety of computer measures can be used as end points in coronary angiographic therapy trials, but change in percent stenosis correlates best with visual panel assessments and best reflects the treatment benefit; when treatment effect sizes are moderate to large, the required sample size of coronary angiographic trials can be reduced when QCA is used.

Adult↗

PubMed1991

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↗

PubMed1991

Arterial wall oxygenation, oxyradicals, and atherosclerosis.

The oxygen supply of inner media and thickened intima of atherosclerosis prone arteries depends largely on diffusion from the endothelium. Conditions which increase wall thickness and oxygen diffusion or reduce oxygen transmissibility produce hypoxia and steep PO2 gradients within the wall. Cerebral injury and myocardial reperfusion studies indicate that intermittent hypoxia and steep PO2 gradients lead to oxyradical formation and tissue damage. Products of lipid and sterol peroxidation are found in atherosclerotic plaques and can be generated by arterial wall cells in culture. It is likely that peroxidation occurs directly within the arterial wall. Sufficient oxyradical generation occurs during normal oxygen metabolism that local scavenger mechanisms are required to avoid tissue damage. Experimental hypertension, hyperlipemia and balloon injury produce medial hypoxia with steep PO2 gradients and redistribution of the pattern of arterial wall antioxidant enzymes. This suggests that minor deviations from normal arterial wall anatomy and function can lead to oxyradicals which can be directly injurious and can amplify the atherogenic potential of lipoprotein infiltration.

Animals↗

PubMed1991

Cholesterol feeding increases plasma and aortic tissue cholesterol oxide levels in parallel: further evidence for the role of cholesterol oxidation in atherosclerosis.

To determine the relationship between plasma and arterial wall oxysterols, plasma and aortic tissue from 7 New Zealand White rabbits fed a high cholesterol (1%) diet for 6 weeks was compared to plasma and aortic tissue from 7 normocholesterolemic rabbits fed standard rabbit chow. Cholesterol and cholesterol oxide fractions were isolated and analyzed by gas chromatography. Normocholesterolemic plasma and aortic tissue contained low levels of cholest-5-ene-3 beta, 7 alpha-diol, cholesta-3,5-dien-7-one, 5,6 alpha-epoxy-5 alpha-cholestan-3 alpha-ol, cholest-5-ene-3 beta, 7 beta-diol, and 5 alpha-cholestane-3 beta, 5,6 beta-triol while hypercholesterolemic plasma and atherosclerotic aorta contained significantly higher levels (P less than 0.05) of these products. Furthermore, 5,6 beta-epoxy-5 alpha-cholestan-3 beta-ol not found in normocholesterolemic plasma or aortic tissue was present in substantial amounts in both hypercholesterolemic plasma and atherosclerotic aortic tissue. Cholest-5-ene-3 beta,25-diol and 3 beta-hydroxycholest-5-ene-7- one not present in normocholesterolemic aorta were present in the atherosclerotic aorta. The oxysterol chromatographic patterns of normocholesterolemic plasma and normocholesterolemic aortic tissue were similar to each other as were the oxysterol chromatographic patterns of hypercholesterolemic plasma and atherosclerotic aortic tissue. The chromatographic patterns between the normocholesterolemic and hypercholesterolemic samples differed however. Possible absorption of the low levels of cholesterol oxides present in the cholesterol feed could account for the elevation of only some of the oxysterols. We conclude that cholesterol oxides exist at some basal level in normocholesterolemia and that these levels are increased by cholesterol-feeding which results in hypercholesterolemia. Our findings demonstrate that there is a strong relationship between plasma and aortic arterial wall levels of cholesterol oxides and suggest that in addition to exogenous sources, formation of cholesterol oxides proceeds via free radical oxidation acting upon elevated cholesterol levels resulting in the accumulation of these potentially cytotoxic and atherogenic products.

Animals↗

PubMed1991

Effects of colestipol-niacin therapy on human femoral atherosclerosis.

The 2-year therapy effect on femoral atherosclerosis was evaluated in the Cholesterol Lowering Atherosclerosis Study (CLAS), a randomized, placebo-plus-diet-controlled angiographic trial of colestipol-niacin therapy plus diet in men with previous coronary bypass surgery. Different diet compositions were prescribed to enhance the differential in blood cholesterol responses between the two groups. The annual rate of change in computer-estimated atherosclerosis (CEA), a measure of lumen abnormality, was evaluated between treatment groups. A significant per-segment therapy effect was found in segments with moderately severe atherosclerosis (p less than 0.04) and in proximal segments (p less than 0.02). When segmental CEA measures were combined into a per-patient score using an adaptation of the National Heart, Lung, and Blood Institute scoring procedure, a significant therapy effect was observed (p less than 0.02). Total variance of the annual change rate in CEA was as predicted from pilot studies, but measurement variation was larger. The therapy effect observed in femoral arteries, although significant, was less marked than the strong and consistent benefit previously reported for both native coronary arteries and aortocoronary bypass grafts.

Arteriosclerosis↗

PubMed1990

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↗

PubMed1990

Flow measurements in a model of the mildly curved femoral artery of man.

Steady flow observations in a smooth curved femoral artery model with a gradual bend revealed a flow pattern like that observed in coiled pipes. A double helical type flow was found to develop, with converging streamlines in the wall vicinity from the upper and lower plane of curvature merging asymptotically along the inner curvature in a stable manner. The helical or swirl angle of the labeled fluid particle paths increased with flow rate and thus Dean number. Flow in the wall vicinity was altered by centrifugal effects almost immediately downstream of the transition from the straight to curved segment for steady flow, although the propagation of this effect was observed farther downstream along the inner curvature side. This observed distance along the inner curvature became shorter with increasing Dean number. Pressure measurements for steady flow revealed progressively larger pressure drops with distance along the entrance region of the curved segment relative to that for a straight lumen. The overall pressure drop or flow resistance increased in a nonlinear way with increasing flow rate and thus Dean number. Time average pressure drop measurements across another similar smooth curved femoral model were found to be about the same for simulation of femoral artery pulsatile flow as for steady flow.

Blood Flow Velocity↗

PubMed1989

Adaptation to arterial wall hypoxia demonstrated in vivo with oxygen microcathodes.

Iliofemoral arteries of 9 rabbits were balloon de-endothelialized resulting in subintimal thickening. Contrary to expectation, enzyme and lactate determinations did not indicate arterial wall hypoxia when compared with arteries of 10 control rabbits. The explanation came from in vivo measurement of oxygen tension profiles across the de-endothelialized and control femoral arteries and from the subsequent histological findings. They showed that the impaired oxygen supply of the de-endothelialized arteries with subintimal thickening was counteracted by a centripetal oxygenation of the arterial wall obviously induced by proliferation of newly formed nutrient vessels in the adventitia. Such adaptation is an important mechanism against hypoxia induced by arterial injury and may be an essential protective factor in atherogenesis.

Animals↗

PubMed1988

The oxygen environment of the arterial media in early rabbit hypertension.

Hypertensive stimuli in experimental animals appear to cause early arterial wall hypermetabolism before hypertension is established and before histomorphic changes are marked. Hypermetabolism and the large diffusion distances for oxygen characteristic of large arteries imply that mural hypoxia could occur early in the disease but this has not been studied. Therefore, we measured aortic wall tissue oxygen distributions in male New Zealand White rabbits 2 weeks (1) after production of upper body hypertension by coarctation of the abdominal aorta, (2) after sham operation, and (3) in normal controls. As compared to normal and sham operated animals, blood pressure in the coarctation animals was significantly elevated from control levels, and the oxygen partial pressures were significantly reduced throughout the media. However, the hypoxic mural oxygen tensions in this relatively thin wall were not low enough to terminate classical respiration. At the time of measurement, moderate microscopic pathology was already present, including increased connective tissue production. The accompanying histomorphic changes are compatible with reports of extrarespiratory oxygen sensitivity of connective tissue metabolism.

Animals↗

PubMed1988

The effect of combined deendothelialization and hypercholesterolemia on some arterial lysosomal and glycolytic enzymes and lactate in rabbits.

In eight New Zealand white male rabbits the abdominal aorta and one iliofemoral artery was balloon deendothelialized (group A). After 2 weeks they were kept for 6 weeks on a high cholesterol diet together with eight unoperated rabbits (group B). Eight more rabbits were kept on a commercial diet only (group C). The degree of atherosclerosis was much higher in the deendothelialized Group A vessels than in the uninjured group B vessels. The activity of lactate dehydrogenase and of the rate-limiting glycolytic pyruvate kinase was significantly increased and the activity of lipoamide dehydrogenase decreased in the group A aortas. In the iliofemoral arteries a similar but statistically insignificant tendency was detected. There was no significant difference, however, in aortic lactate between the three groups. Thus, local hypoxia did not significantly contribute to the high degree of atherosclerosis in the group A animals in spite of the enzyme activity differences. Previous experience of the authors, using arterial microcathode pO2 measurements, indicates that following deendothelialization an adaptive proliferation of nutrient vessels and increased arterial oxygenation takes place. The average activity of the lysosomal N-acetyl-beta-glucosaminidase was five times and that of beta-glucuronidase, seven times higher in the Group A than Group B aortas; in the iliofemoral arteries the differences were even larger. The huge elevation of these hydrolases, which are involved in glycosaminoglycan catabolism, provides indirect indication that accumulation of glycosaminoglycans and possibly their ability to form complexes with apoB-containing lipoproteins played a major role in the much increased degree of atherosclerotic lesions in the Group A rabbits.

Animals↗

PubMed1988

Flow measurements in a human femoral artery model with reverse lumen curvature.

Flow visualization and wall pressure measurements were made in a smooth reverse curvature model that conformed to the gentle "s" shape of a left femoral artery angiogram of a patient in a clinical trial. Observed lesion localization at the inner (lesser) curvatures appeared to be associated with secondary flows in the wall vicinity directed toward the inner curvatures that tended to reverse direction in the flow entering the reverse curvature region. Moderate flow resistance increases of about 20 percent above the Poiseuille flow relation were found at the higher physiological Reynolds numbers Re above about 600-700 and thus Dean numbers for steady flow. For pulsatile flow simulation, flow resistances did not increase up to the largest Re of 470 tested. Apparently, the large variations in velocity during the cardiac cycle disrupted the stronger secondary flow patterns observed at the higher Reynolds numbers for steady flow.

Arteriosclerosis↗

PubMed1988

Flow measurements in an atherosclerotic curved, tapered femoral artery model of man.

Flow visualization and pressure measurements were made for physiological conditions in a model derived from a femoral angiogram of a patient with lesion localization on the inner curvature wall and with vessel taper. Effects of curvature and taper were evaluated separately in other curved, tapered, smooth and straight, tapered, smooth models. Double helical secondary flow patterns were modified by plaque on the inner wall, and flow separations were observed between plaques at higher flow rates and Reynolds numbers. Pressure drop data for the plaque simulation model were similar in trend with Reynolds number as for the smooth model, but flow resistances were 25 to 40 percent higher. Significant pressure drops were measured due to the mild taper which could be estimated from momentum considerations, and smaller increased pressure drops were found due to curvature effects at the higher Dean numbers. Flow resistances for in vivo pulsatile flow simulation were about 10 percent higher than for steady flow for the plaque model, whereas no differences were observed for the smooth model.

Arteriosclerosis↗