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Biomedical subjects

R L Sims

Publications and source records attributed to R L Sims.

14 recordsLinked to original sources

Intimal hyperplasia and wall shear in arterial bypass graft distal anastomoses: an in vivo model study.

The observation of intimal hyperplasia at bypass graft anastomoses has suggested a potential interaction between local hemodynamics and vascular wall response. Wall shear has been particularly implicated because of its known effects upon the endothelium of normal vessels and, thus, was examined as to its possible role in the development of intimal hyperplasia in arterial bypass graft distal anastomoses. Tapered (4-7 mm I.D.) e-PTFE synthetic grafts 6 cm long were placed as bilateral carotid artery bypasses in six adult, mongrel dogs weighing between 25 and 30 kg with distal anastomotic graft-to-artery diameter ratios (DR) of either 1.0 or 1.5. Immediately following implantation, simultaneous axial velocity measurements were made in the toe and artery floor regions in the plane of the anastomosis at radial increments of 0.35 mm, 0.70 mm, and 1.05 mm using a specially designed 20 MHz triple crystal ultrasonic wall shear rate transducer Mean, peak, and pulse amplitude wall shear rates (WSRs), their absolute values, the spatial and temporal wall shear stress gradients (WSSG), and the oscillatory shear index (OSI) were computed from these velocity measurements. All grafts were harvested after 12 weeks implantation and measurements of the degree of intimal hyperplasia (IH) were made along the toe region and the artery floor of the host artery in 1 mm increments. While some IH occurred along the toe region (8.35+/-23.1 microm) and was significantly different between DR groups (p<0.003), the greatest amount occurred along the artery floor (81.6+/-106.5 microm, mean +/- S.D.) (p < 0.001) although no significant differences were found between DR groups. Linear regressions were performed on the paired IH and mean, peak, and pulse amplitude WSR data as well as the absolute mean, peak, and pulse amplitude WSR data from all grafts. The mean and absolute mean WSRs showed a modest correlation with IH (r = -0.406 and -0.370, respectively) with further improvements seen (r = -0.482 and -0.445, respectively) when using an exponential relationship. The overall best correlation was seen against an exponential function of the OSI (r = 0.600). Although these correlation coefficients were not high, they were found to be statistically significant as evidenced by the large F-statistic obtained. Finally, it was observed that over 75 percent of the IH occurred at or below a mean WSR value of 100 s(-1) while approximately 92 percent of the IH occurred at or below a mean WSR equal to one-half that of the native artery. Therefore, while not being the only factor involved, wall shear (and in particular, oscillators wall shear) appears to provide a stimulus for the development of anastomotic intimal hyperplasia.

Anastomosis, Surgical↗

The relationship between employee attitudes and conflicting expectations for lying behavior.

In this study, the author explores the relationship between conflicting ethical expectations for lying behavior and employee attitudes. In a sample of 140 full-time employees, the findings indicated that as the difference between formal codes of ethics and supervisor expectations for lying behavior increases, intentions to turnover and expressed feelings of intrapersonal role conflict increase, and job and organizational satisfaction and affective commitment decrease. However, conflicting ethical expectations were not significantly associated with a commitment to continue in the job.

Adult↗

The effect of graft caliber upon wall shear within in vivo distal vascular anastomoses.

Wall shear has been widely implicated as a contributing factor in the development of intimal hyperplasia in the anastomoses of chronic arterial bypass grafts. Earlier studies have been restricted to either: (1) in vitro or computer simulation models detailing the complex hemodynamics within an anastomosis without corresponding biological responses, or (2) in vivo models that document biological effects with only approximate wall shear information. Recently, a specially designed pulse ultrasonic Doppler wall shear rate (PUDWSR) measuring device has made it possible to obtain three near-wall velocity measurements nonintrusively within 1.05 mm of the vessel luminal surface from which wall shear rates (WSRs) were derived. It was the purpose of this study to evaluate the effect of graft caliber, a surgically controllable variable, upon local hemodynamics, which, in turn, play an important role in the eventual development of anastomotic hyperplasia. Tapered (4-7 mm I.D.) 6-cm-long grafts were implanted bilaterally in an end-to-side fashion with 30 deg proximal and distal anastomoses to bypass occluded common carotid arteries of 16 canines. The bypass grafts were randomly paired in contralateral vessels and placed such that the graft-to-artery diameter ratio, DR, at the distal anastomosis was either 1.0 or 1.5. For all grafts, the average Re was 432 +/- 112 and the average Womersley parameter, alpha, was 3.59 +/- 0.39 based on artery diameter. There was a sharp skewing of flow toward the artery floor with the development of a stagnation point whose position varied with time (up to two artery diameters) and DR (generally more downstream for DR = 1.0). Mean WSRs along the artery floor for DR = 1.0 and 1.5 were found to range sharply from moderate to high retrograde values (589 s-1 and 1558 s-1, respectively) upstream to high antegrade values (2704 s-1 and 2302 s-1, respectively) immediately downstream of the stagnation point. Although there were no overall differences in mean and peak WSRs between groups, there were significant differences (p < 0.05) in oscillatory WSRs as well as in the absolute normalized mean and peak WSRs between groups. There were also significant differences (p < 0.05) in mean and peak WSRs with respect to axial position along the artery floor for both DR cases. In conclusion, WSR varies widely (1558 s-1 retrograde to 2704 s-1 antegrade) within end-to-side distal graft anastomoses, particularly along the artery floor, and may play a role in the development of intimal hyperplasia through local alteration of mass transport and mechano-signal transduction within the endothelium.

Analysis of Variance↗

Controlled delivery of vascular endothelial growth factor promotes neovascularization and maintains limb function in a rabbit model of ischemia.

PURPOSE: Vascular endothelial growth factor (VEGF) modulates new blood vessel development and growth and has been suggested as a potential therapeutic agent that could alleviate debilitating claudication in patients. The objective of this study was to determine whether controlled, local delivery of a low dose of VEGF from an osmotic pump could promote neovascularization, limb perfusion, and functional improvements in the hind limbs of rabbits rendered partially ischemic by surgery. The effects of VEGF were compared with those of the vasodilator nitroglycerin (NTG) and to saline administered similarly. METHODS: Thirty rabbits were randomly assigned to either VEGF (n = 10), NTG (n = 10), or saline (n = 10) treatment groups. Partial ischemia was induced in each left hind limb by surgical ligation of the common and superficial femoral arteries, leaving the internal iliac artery intact. The right limb of each animal served as a nonischemic control. Immediately after vessel ligations, a 28-day osmotic pump was implanted to deliver VEGF (0.22 microg/kg/day), NTG (17.8 microg/kg/day), or saline solution into the common iliac artery just proximal to the ligation site. Comparative vascularity between ischemic and nonischemic limbs within treatment groups and between groups was evaluated by (1) capillary counts from representative fields of hematoxylin and eosin stained muscle tissue taken from hind limbs at day 40; (2) digitized arteriograms of ischemic legs at day 40, which were used to quantify the complexity of vascular branching (fractal dimension index) and the total extent of vascularization (vascular density index); (3) measuring capillary refill times in ischemic limbs; and (4) observations of functional and trophic changes in ischemic limbs. Statistical differences between treatment groups were evaluated by one-way ANOVA. RESULTS: Complexity of vascular branching and vascular density were significantly greater (p < 0.001) in VEGF-treated ischemic limbs compared with NTG- and saline-treated ischemic limbs. By postoperation day 14, all VEGF-treated ischemic limbs had restored capillary refill (p < 0.001), new hair growth, and greatly improved limb function and appearance. Saline-treated limbs exhibited ischemic changes, with poor capillary refill and negligible limb function. Capillary refill in NTG-treated ischemic limbs did not differ significantly from saline-treated limbs. Ischemic VEGF-treated limbs had significantly more capillaries compared with both ischemic and nonischemic limbs in saline-treated animals (p < 0.05). Ischemic NTG-treated limbs also had significantly more capillaries compared with ischemic limbs in saline-treated animals (p < 0.05). Because of high variability, however, capillary counts in VEGF-treated ischemic limbs did not differ significantly from those of contralateral nonischemic limbs, or from capillary counts in either ischemic or nonischemic limbs of NTG-treated rabbits. CONCLUSIONS: Controlled release of microgram quantities of VEGF significantly enhanced neovascularization and vascular perfusion in ischemic limbs compared with controls in this rabbit model of partial ischemia. In addition, VEGF-treated ischemic limbs demonstrated near-normal function and appearance, whereas NTG- and saline-treated ischemic controls remained noticeably impaired. This novel approach of VEGF delivery may prove clinically useful either alone or combined with revascularization procedures.

Analysis of Variance↗

Pharmacologic modulation of intimal hyperplasia in canine vein interposition grafts.

PURPOSE: The purpose of this study was to evaluate the efficacy of three drugs (cilazapril, cyclosporine, and aspirin) in modulating the progression of intimal hyperplasia during short postoperative times in short-segment, autogenous vein bypass grafts in a canine model. The relative effects of the drugs on the progression of intimal hyperplasia were compared with the Gilman parameter, a measure used extensively as a wound healing descriptor. To our knowledge this is the first use of the Gilman parameter in assessing vascular disease. METHODS: Seventy-two conditioned mongrel dogs were randomly and equally divided according to a three-factor analysis of variance. The factors included (1) drug treatments (cilazapril [10 mg/kg/day], cyclosporine [4 mg/kg/day], aspirin [325 mg/day], and control [nonmedicated]), (2) implantation sites (femoral and carotid arteries), and (3) postoperative times of graft harvest (1, 3, and 6 weeks). Each dog had 2 cm segments of autogenous jugular vein interpositioned bilaterally into each of the paired carotid and femoral arteries. Quantitative data on luminal narrowing over time from intimal hyperplasia were compared from calculated Gilman parameters after image analysis of retrieved, histologically processed graft sections. RESULTS: The observed variability in the data was attributed to drug treatments and time. At 1 week after operation the mean Gilman parameters did not differ significantly among the treatment groups in either midgraft or distal graft segments. At 3 weeks the mean Gilman parameters of midgraft and distal graft sections of cyclosporine-treated dogs differed significantly (p < 0.05) from those of the control group and the cilazapril and aspirin-treated groups, which did not differ from each other. At 6 weeks after operation, mean Gilman parameters from aspirin- and cyclosporine-treated dogs differed statistically from control and cilazapril-medicated dogs and from each other (p < 0.001). CONCLUSIONS: These data support the efficacy of aspirin and cyclosporine in reducing intimal hyperplasia in short-segment arterialized vein grafts during short postoperative periods. Additional studies are required to ascertain whether the beneficial effects of aspirin and cyclosporine persist long-term.

Animals↗

A canine model of intimal hyperplasia (IH) in autogenous vein grafting: a preliminary report.

High failure rates (10-40% at 1 year and 2-6% per year thereafter) of autologous vein grafts in peripheral bypass surgery due to progressive intimal hyperplasia (IH) have prompted researchers to search for an animal model that develops IH in a relatively short period of time. This study summarizes our experiences in promoting IH in a canine model. Eight to ten centimeters of both jugular veins were exposed in 40 adult mongrel conditioned dogs. After division into 4-5-cm lengths, the segment of jugular vein most proximal was ballooned at 800-900 mm Hg with a modified 8F Fogarty catheter to induce intimal and medial layer injury. The distal segment was left nonballooned. Segments of these autologous vein grafts, 1.5 cm in length, both ballooned and nonballooned, were then anastomosed, end to end, into the carotid and femoral circulations. Six weeks postoperatively the grafts were perfusion-fixed, harvested, and histologically processed, and the amount of the lumen in midgraft sections occupied by IH was determined by image analysis. In all dogs, the degree of IH was significantly greater in the balloon catheterized vs noncatheterized graft segments. IH was more severe in the femoral than in the carotid arteries. The grafts that developed the most severe intimal hyperplasia were femoral grafts that had been balloon catheterized. We conclude that these protocols are effective in inducing IH in a canine model in short postoperative times.

Animals↗

Manganese content of the cellular components of blood.

We measured the manganese content of whole blood, plasma, platelets, mononucleated cells, polymorphonucleated cells, and erythrocytes. Platelets and blood cells were separated from whole blood by use of discontinuous gradients of colloidal polyvinylpyrrolidone-coated silica (Percoll), and their manganese content was measured by Zeeman graphite furnace atomic absorption spectrophotometry, after digestion with nitric acid and hydrogen peroxide. Erythrocytes account for about 66% of the manganese in whole blood, whereas the "buffy coat"--platelets and leukocytes--accounts for about 30%. The "buffy coat" components turn over more rapidly than do erythrocytes, so their manganese content may better indicate the body's manganese status.

Adult↗

Rationing has begun.

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Health Care Rationing↗

Fighting back.

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Data Collection↗

Severe zinc deficiency: effects on the distribution of nine elements (potassium, phosphorus, sodium, magnesium, calcium, iron, zinc, copper and manganese) in regions of the rat brain.

The effect of severe zinc deficiency on the distribution of nine elements (potassium, phosphorus, sodium, magnesium, calcium, iron, zinc, copper and manganese) in brain regions (olfactory lobes, right and left hippocampi, cerebellum and the rest of the brain) has been studied. After male rats (30 days old) were fed a zinc-deficient diet for 28 days, the zinc concentration of most brain parts was similar to zinc-adequate control values. Olfactory lobe zinc, on the other hand, was slightly depressed. However, the levels of other metals were dependent on zinc nutriture. Zinc deficiency caused an elevation in copper concentrations in most brain parts. Restriction of food intake caused a similar increase in brain copper but generally the effect was less than with zinc deficiency. Levels of calcium, manganese, sodium and potassium, in certain brain regions, also appeared to be altered by the zinc status of an animal. Of the minerals examined, only zinc and copper displayed asymmetrical distribution between the right and left hippocampus, and severe zinc deficiency did not affect lateral distribution of these trace metals in the hippocampus. The data suggest the hypothesis that changes in brain metal content, associated with zinc deficiency, contribute to the behavioral abnormalities that occur.

Animals↗

HSA fosters hospitals' voluntary cooperation in areawide planning.

An HSA convinced the 31 hospitals in its health service area to participate in a voluntary moratorium on expansion and a voluntary planning process through which their long-range institutional plans are reviewed for incorporation into the HSA's areawide plans.

Community Participation↗

Effect of simultaneous thiamin and riboflavin deficiencies on the determination of transketolase and glutathione reductase.

Thiamin and/or riboflavin status have been assessed in rats simultaneously deprived of both vitamins and subsequently repleated with either one or the other in succession. Undernutrition in control rats was found to depress the activity of the erythrocyte enzymes (transketolase and glutathione reductase, respectively) used to assess status. On the other hand, the activity coefficients obtained by in vitro stimulation of the enzymes with their respective missing cofactors were not suppressed. Therefore the activity coefficients were superior indices of thiamin and riboflavin nutriture compared to the enzyme activities. When activity coefficients were used as the indices of vitamin status there did not appear to be interference from the simultaneous deficiency of the alternate vitamin. Apparent interference was encountered when the enzyme activity itself was used as the criteria.

Animals↗