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Biomedical subjects

K C Wright

Publications and source records attributed to K C Wright.

At least 55 records · Page 3Linked to original sources

Clot embolic stroke in the vertebrobasilar system of rabbits: a transfemoral angiographic technique.

Previous animal models of thromboembolic stroke have focused upon the carotid artery system. An alternative approach utilizing the vertebrobasilar system in rabbits is presented here. Left vertebral artery catheterization was accomplished relatively simply in this model using transfemoral angiographic techniques. Twenty-four-hour-old clot emboli with calculated volumes in the range of 0.007-0.11 cc were delivered by this route and found to lodge at the juncture of the basilar tip and the Circle of Willis in 11 of 13 rabbits. Intra-arterial infusion of streptokinase in one animal resulted in angiographically complete clearing of clot. Certain technical advantages in this particular approach are discussed.

Animals↗

Experimental comparison between hepatic artery infusion and occlusion-infusion of adriamycin.

Adult mongrel dogs were used to compare hepatic arterial infusion and arterial occlusion-infusion with regard to local and systemic Adriamycin levels. The drug was infused into the right proper hepatic artery of each dog after occlusion of the gastroduodenal artery. Blood and tissue samples were collected at regular intervals for Adriamycin determination. Four weeks later, each dog again received the same agent in the right proper hepatic artery, but this time arterial flow was blocked with an inflated balloon during drug infusion (arterial occlusion-infusion). Blood and tissue drug levels were determined and compared with those obtained using infusion without occlusion. Results indicate that when Adriamycin is administered into the hepatic artery of dogs, occlusion-infusion produces significantly greater hepatic venous drug levels, drug uptake, and drug metabolism than does infusion alone.

Animals↗

Flexible balloon-expanded stent for small vessels. Work in progress.

A new type of flexible, balloon-expanded, stainless steel stent was designed for introduction into small vessels subject to motion. Four stents placed in four dogs were patent at follow-up (4-8 weeks). A fibrocellular proliferation involving the intima and media was responsible for a 20%-25% luminal narrowing observed in all vessels with stents. The stent has longitudinal flexibility, which should permit its insertion into small peripheral, visceral, and coronary arteries.

Animals↗

Self-expanding metallic stents for small vessels: an experimental evaluation.

Thirty-three self-expanding metallic stents were placed in 24 arterial segments of the hind legs and nine arteries of the abdominal viscera in seven dogs. Twelve 5-mm stents, eight 4-mm stents, and 13 3-mm stents were inserted. Follow-up ranged from 4 to 30 weeks. All 4-mm and 5-mm stents were patent at follow-up. Seven (54%) of the 3-mm stents remained patent. Stent wires were completely covered by a proliferation of the intima. No stent migration, occlusion of side branches, or vessel wall perforation was observed. A stent/artery ratio (SAR) was computed using stent and recipient vessel diameters. Good vascular patency was observed when the SAR was less than or equal to 1.2. An SAR greater than 1.2 was associated with immediate spasm, immediate or delayed thrombosis, or excessive intimal proliferation. Selection of correct stent size is a major determinant of patency in small arteries.

Angiography↗

Percutaneous endovascular graft: experimental evaluation.

An arterial endovascular graft was constructed by wrapping a Dacron cylinder around the Gianturco expandable metallic stent. The device was passed through an 11-F Teflon catheter into the normal abdominal or thoracic aortas of nine dogs. At follow-up of 7-35 weeks, all but one graft remained patent. At necropsy, the grafts were almost completely covered by neo-intimal proliferation. Similar proliferation was observed between the graft and the wall of the vessel.

Aneurysm↗

Self-expanding metallic stents: preliminary evaluation in an atherosclerotic model.

The performance of the self-expanding stainless steel (Gianturco) stent in atherosclerotic arteries was examined in a rabbit model. Atherosclerosis was induced by supplementing rabbit chow with 6% peanut oil and 2% cholesterol followed by endothelial disruption of the abdominal aorta with a balloon catheter and continuation on the atherogenic diet for the remainder of the study. Eighteen stents, 1 cm in length and 4 or 5 mm in diameter when fully expanded, were placed in atherosclerotic stenotic lesions in six rabbits. Luminal distention was consistently achieved. At 8 weeks follow-up, no luminal narrowing, stent migration, thrombus formation or branch vessel occlusion had occurred. Atherosclerotic neointimal proliferation occurred around the stent wires following placement, but did not cause significant luminal narrowing.

Animals↗

Experimental combination chemotherapy: intracarotid versus intravenous administration of aziridinylbenzoquinone, BCNU, and cisplatin in dogs.

Sixteen adult beagles (10-12 kg) were used to evaluate combinations of 2,5-diaziridinyl-3,6-biscarboethoxyamino-1,4-benzoquinone (AZQ, aziridinylbenzoquinone), 1,3-bis-2-chloroethyl-1-nitrosourea (BCNU, carmustine), and cis-dichlorodiammineplatinum(II) (CDDP, cisplatin) administered by intravenous or intracarotid infusion. Moderate to severe systemic toxicities resulted from all drug infusions, but no histopathologic changes were found in the central nervous system (CNS) of any of the dogs. Results indicated that the toxicities were not dependent on the route of administration or the recipient's gender, and they were reversible in most cases with intravenous supportive therapy. Cisplatin seemed to have an additive effect when administered in combination with AZQ and/or BCNU.

Animals↗

Strength testing with a portable dynamometer: reliability for upper and lower extremities.

This study was designed to determine intraobserver and interobserver reliability of maximal muscle strength for upper and lower extremity muscle groups. Four healthy subjects were tested with a portable muscle dynamometer on two separate occasions by three separate examiners to determine maximal isometric strength of lateral pinch between thumb and index finger, elbow flexion, elbow extension, shoulder flexion, hip flexion, hip extension, hip abduction, knee flexion, and ankle dorsiflexion. A break test was also used to evaluate the strength of cervical flexor muscles and extensor hallucis longus. Pearson correlation coefficients for inter- and intraexaminer testing was good for upper extremity test values from 0.85 to 0.99. The variation coefficient of the methodology error (CV) in all upper extremity muscle tests was between 5.1% and 8.3%. These results seemed reliable for clinical muscle strength testing. However, correlation coefficients for lower extremity testing were poor, with values ranging from -0.20 to 0.96. The CV in these tests was much greater than in the upper extremities and ranged from 11.3% to 17.8%. Both break tests also had high CV, with each being greater than 17%. Our results demonstrate that although the dynamometer is reliable for testing upper extremity muscle groups, it is unreliable for testing lower extremity muscle groups. Further work is needed to evaluate muscle strength quantitatively in the clinical setting in an accurate, valid, and reliable manner.

Arm↗

Pulsed arterial infusions. Chemotherapeutic implications.

To simulate the intra-arterial infusion of chemotherapy, ink was infused at a steady rate through a vascular catheter inserted in a transparent tube carrying water at a rate similar to that of arterial blood. The ink ran in one or two discrete streams for 10 to 15 cm before mixing with the water, and there were substantial differences in the concentrations of ink in the water collected from side holes made at various distances from the catheter tip. If the ink was delivered in short pulses, however, it mixed with the water 2 to 3 cm beyond the catheter tip, and the samples collected from the side holes showed similar concentrations of ink. A similar situation may be encountered when chemotherapeutic agents are infused into patients. Therefore, pulsation may produce a more homogeneous drug distribution in the infused tissue. The in vitro data was substantiated in patients by the following: (1) the intra-arterial administration of technetium 99m(99mTc)labeled macroaggregated albumin (MAA) by both steady and pulsed infusions; and (2) changes in the severity of inflammatory skin reactions frequently associated with intra-arterial chemotherapy of the extremities. Improved isotope distribution was noted in 19.3% of the liver and 40% of the extremity studies. Reduced skin reactions were observed in approximately 90% of the extremities receiving pulsed chemotherapeutic infusions.

Antineoplastic Agents↗

Tracheobronchial tree: expandable metallic stents used in experimental and clinical applications. Work in progress.

An expandable stainless steel stent was formulated for use in the treatment of tracheobronchial stenosis, tracheomalacia, and airway collapse following tracheal reconstruction. The stents were placed through an endotracheal tube into the trachea and bronchi of 11 healthy dogs. The stents expanded over time, substantially increasing the diameter of the lumen. Slight migration occasionally occurred, while an inflammatory reaction was noted in each animal. The stents were successfully used in the treatment of two cancer patients to dilate a postoperative bronchial stenosis that caused pneumonia and to support a tracheal graft that collapsed with respiration. Because of the stent migration in experimental studies, designs are being tested to develop stents with greater stability. These stents may be effective in overcoming stenosis caused by scarring, extrinsic compression, and collapse of reconstructed tracheobronchial structures.

Adult↗

Stenosis of the vena cava: preliminary assessment of treatment with expandable metallic stents.

To test the ability of Gianturco expandable metallic stents to dilate and maintain patency in stenotic venae cavae, stenosis of the inferior vena cava was created in seven mongrel dogs by the percutaneous injection of absolute ethanol into the paravascular retroperitoneal space. Gianturco stents, placed across the stenotic segment, resulted in successful dilatation with improved hemodynamics in four dogs. The stents failed to dilate an occluded vena cava in one dog; in the remaining dogs, stent placement was complicated by early migration and occlusion. Gianturco stents were placed in two patients, one with superior vena cava syndrome and one with retroperitoneal fibrosis that obstructed the inferior vena cava, and resulted in immediate relief of presenting symptoms. These results should be viewed cautiously, but further investigation into the clinical use of the stents is indicated, especially for patients for whom other treatments are difficult.

Animals↗

An experimental evaluation of microcapsules for arterial chemoembolization.

Microcapsules, 106 micron (range, 50-350 micron), of different capsular materials (monoglyceride, monodiglyceride, natural wax, cellulose polymer, or lactic acid polymer) with and without floxuridine (2'-deoxy-5-fluorouridine, FUDR) were intraarterially injected into dog kidneys. The drug-release characteristics of the microcapsules, as determined by analysis of renal and systemic venous blood samples over a 6-hour period, were uniphasic or multiphasic depending on the capsular material. Histologic changes of varying degrees were noted in all kidneys embolized except for those subjected to capsules of the cellulose polymer. The most striking changes were produced by the lactide polymer capsules. The potential applications of microencapsuled chemotherapeutic agents in intraarterial transcatheter treatment of cancer are discussed.

Animals↗

Experimental enhancement of drug uptake using short-term flow occlusion: a comparison of balloon and tourniquet techniques.

Three groups of dogs, four per group, were used to examine the safety of short-term arterial flow occlusion and potential benefits of balloon and/or tourniquet occlusion-infusion techniques. In part 1, local plasma gases and pH were monitored during a 1-hr period of vascular occlusion. Tourniquet occlusion was found to significantly (p = 0.01) lower pO2. In part 2, local muscle and venous blood samples were obtained during and after a 30-min intraarterial infusion of floxuridine (FUDR). A tourniquet was added to try to eliminate collateral circulation. Local FUDR concentration was increased by 1.3 times in muscle and 19.6 times (p less than 0.01) in ipsilateral femoral vein serum when a tourniquet was added to arterial balloon occlusion-infusion. In addition, the combination of the two occlusion techniques produced a 4.1-fold reduction (p less than 0.05) in systemic venous FUDR levels during infusion when compared to balloon occlusion.

Animals↗

Autonomic dysreflexia in a paraplegic man with catecholamine-secreting neuroblastoma.

Autonomic dysreflexia and catecholamine secreting tumor, each of which causes paroxysmal hypertension, coexisted in a young man. Two years after neuroblastoma was diagnosed, he developed T4 incomplete paraplegia due to metastases to the spine at T5 and L3 levels. Shortly after the onset of paraplegia, paroxysmal hypertension developed. The hypertension was controlled adequately by good bowel and bladder management and oral clonidine. The paroxysmal hypertension is believed to have resulted from the synergistic effect of the high levels of circulating catecholamines from the tumor and the disruption of autonomic pathways.

Adult↗

Percutaneous endovascular stents: an experimental evaluation.

Percutaneous, expanding, endovascular stents were constructed of stainless steel wire formed in a zig-zag pattern. Stents were placed for varying periods of time in the jugular vein, vena cava, and abdominal aorta in each of five adult dogs. The dilating force of the stents could be controlled by different wire size, number and angle of wire bends, and stent length. In addition, multiple stents could be placed one inside the other or one after the other, depending on the circumstance. The stents distended the vessels and increased their diameter. No flow defects, luminal narrowing, or occlusion were noted in any of the stented vessels, even after 6 months. Side branches bridged by the stents remained patent and showed no indication of narrowing. Stent wires became encased by a proliferation of the tunica intima where they contacted the vessel wall. Encasement was slower and less extensive in the abdominal aorta. No vascular erosion or clot formation was found to be associated with any of the stents.

Animals↗

Endovascular stent for use in aortic dissection: an in vitro experiment.

Injection of normal saline and contrast material into the walls of aortic specimens from human cadavers created a narrowing of the aortic lumen, simulating aortic dissection. Endovascular stents were applied to expand the aortic lumen. Successful dilatation of the narrowed aortic lumen was demonstrated in all six specimens.

Aortic Dissection↗

Treatment of the rabbit V-2 carcinoma with intralesional cisplatin.

New Zealand white rabbits were used in the evaluation of intralesional injections of cisplatin for the management of experimentally induced V-2 carcinomas. The tumors were implanted into the right hip by intramuscular injections of an inoculum containing freshly harvested V-2 fragments which gave rise to a single, spherical mass (2-3 cm) 2 weeks after inoculation. All rabbits received two courses of either intralesional cisplatin or saline beginning 2 weeks after inoculation. Cisplatin injections significantly slowed the growth and spread of the primary tumor in all treated rabbits. In addition, intralesional chemotherapy prevented the development of lung metastases in 71% of the animals and produced approximately a threefold increase in survival time. Results indicate that not only is cisplatin active against experimentally induced V-2 carcinomas in rabbits, but direct intralesional injection is also an easy and effective means of administering chemotherapy.

Animals↗