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Biomedical subjects

K C Wright

Publications and source records attributed to K C Wright.

At least 19 recordsLinked to original sources
PubMed1992

Halogenated analogues of tamoxifen: synthesis, receptor assay, and inhibition of MCF7 cells.

This study was conducted to develop a ligand for imaging estrogen-receptor-positive breast tumors by positron emission tomography or single photon emission computed tomography. We synthesized fluoro and iodo analogues of tamoxifen, and these halogenated analogues produced greater affinity for binding to the receptor than tamoxifen. Values of the inhibition affinity constants were as follows: tamoxifen, 15,000 nM; fluoromethyl-N,N-diethyltamoxifen, 2500 nM for the cis isomer and 500 nM for the trans isomer; and iodomethyl-N,N-diethyltamoxifen, 1500 nM for the cis isomer and 1000 nM for the trans isomer. In studies of human MCF7 breast tumor cell growth, concentrations that inhibited tumor growth in 50% of the cases were as follows: tamoxifen, 11 microM; fluoromethyl-N,N-diethyltamoxifen, 4.5 and 11.8 microM for the cis and trans isomers, respectively; and iodomethyl-N,N-diethyltamoxifen, 2.4 and 6.3 microM for the cis and trans isomers, respectively. These studies suggest that both fluoro and iodo analogues of tamoxifen may be useful diagnostic compounds for predicting the response of estrogen-receptor-positive breast tumors to tamoxifen analogues used in chemotherapy.

Animals↗
PubMed1992

Use of the Gianturco self-expanding stent in stenoses of the superior and inferior venae cavae.

Twenty-eight patients with severe superior and inferior vena cava syndromes were treated with self-expandable Gianturco stents. Nineteen patients responded, seven did not respond, and two were unevaluable. Fourteen of the 19 who responded had complete or near complete resolution of their syndrome, and five had a partial remission. Five of the responders did not derive any benefit from stent placement because of additional problems that led to their death within 3 weeks of the stent placement procedure. The main cause for failure was the relatively weak expansile force of the stent. Complications included stent migrations without untoward effects in one patient, stent misplacement in one patient, fracture of the stent wire in two patients, and hemorrhage that could be attributed to the stent in one patient. This uncontrolled study suggests that caval obstruction syndromes in some patients may be effectively palliated with Gianturco stents.

Adult↗
PubMed1992

Development and initial experimental evaluation of a prosthetic aortic valve for transcatheter placement. Work in progress.

A prosthetic caged-ball aortic valve that can be placed with transcatheter techniques was designed, constructed, and initially evaluated in 12 adult mongrel dogs. The prosthesis consisted of a ring, cage, and ball. The ring was made of stainless steel wire coiled in a springlike configuration and covered with an expandable nylon mesh. The cage consisted of a self-expanding Gianturco stent with flat stainless steel wires attached across the cranial end. The ball was a detachable latex balloon filled with a radiopaque silicone prepolymer system. The self-expanding valve was easily passed through an 11- or 12-F Teflon sheath and was placed in the ascending aorta by means of the carotid approach. The stability and efficacy of the prosthesis were evaluated radiographically for as long as the valve remained functional (1-3 hours). The competency of the valve and the patency of the coronary arteries were determined angiographically over the same period. The results of these studies indicate that development and transcatheter placement of a prosthetic aortic valve are feasible.

Animals↗
PubMed1991

Synthesis and in vitro receptor binding studies of fluorotamoxifen analogues.

We describe the synthesis of new fluorotamoxifen analogues with the fluorine atom positioned on the end of the aliphatic chain of tamoxifen. The binding of fluorotamoxifens to cytosol estrogen receptors of rat uteri was determined with [3H]estradiol (5 nM). The fluorotamoxifens had similar or superior binding affinities compared with tamoxifen. The IC50 value was as follows: tamoxifen, 5 x 10(-7) M; fluorotamoxifen (VII), 5 x 10(-7) M; N,N-diethylfluorotamoxifen (IV)-cis, 1 x 10(-6) M, and trans, 2 x 10(-7) M; and (cis) fluoromethyl-N,N-diethyltamoxifen (VI) 1 x 10(-7) M. Therefore, the fluorinated tamoxifens have potential use in imaging estrogen receptors by PET.

Animals↗
PubMed1991

Injection of a silicone prepolymer system into the gallbladder of rabbits.

The aim of this study was to assess the feasibility of a new nonsurgical treatment for cholelithiasis. This involved injecting a liquid prepolymer into the gallbladder which would polymerize in situ, entrapping existing gallstones and permanently filling the gallbladder so as to prevent subsequent gallstone formation. Initially, several silicone prepolymer mixtures were tested in vitro for viscosity, cure time, radiopacity, and consistency when polymerized. The optimal system with regard to these parameters consisted of two room temperature vulcanizing silicones (3110 and 200), a catalyst (F), and barium sulfate. This mixture was then injected into beakers containing human gallstones alone and in combination with bile, and was periodically evaluated over six months. It was also injected into the gallbladder of six rabbits and left for 12 weeks. No clinical complications were noted in any of the animals. The cured silicone system maintained its original shape and did not fragment. At necropsy, the casts were free in the rabbits' gallbladders, with small accumulations of biliary sludge adhered to their surfaces. No mucocele of the gallbladder was found in any of the rabbits. Cholecystic histology was normal in all cases, and only one animal exhibited a mild chronic portal triaditis. These promising results indicate the need for further studies of the technique and refinement of the silicone formulation.

Animals↗
PubMed1991

Prostatic urethra dilatation with the Gianturco self-expanding metallic stent: a feasibility study in cadaver specimens and dogs.

In an effort to develop a transcatheter technique for dilatation of the prostatic urethra without the use of balloons, the feasibility of using Gianturco self-expanding stents was evaluated. Initially, eight human cadaveric prostatic urethras were stented to evaluate the ability of the stent to dilate the lumen. In all cases, the device attained its unconstrained diameter immediately on placement. Subsequently, stents were placed in the prostatic urethra of 12 dogs and followed up for 1 month (four dogs), 3 months (one dog), and 6 months (seven dogs). Five bare straight-end prostheses, one nylon-covered straight-end device, and six flared-end stents were used. Three of the bare straight-end stents migrated during the follow-up, whereas the nylon-covered and flared-end stents did not. Stent diameters greater than 1.3 times the urethral diameter caused moderate to marked edema and inflammation. After 6 months, white deposits were found on the solder points, presumably from electrolysis. Our experience suggests that placement of Gianturco self-expanding stents may be a useful method of dilating and maintaining the luminal diameter of the prostatic urethra, although care must be taken to select the proper stent size.

Adult↗
PubMed1990

Liposome distribution after intravenous and selective intraarterial infusion in dogs.

In an effort to improve hepatic uptake of liposomes for drug delivery, empty vesicles were administered by means of selective arterial infusion. Negatively charged, multilamellar liposomes were labeled with technetium-99m and infused into healthy adult dogs. Each dog received 100 mg/m2 of lipid over 10 minutes at 2 mL/min. Liposomes were administered via the common hepatic artery after proximal occlusion of the gastroduodenal artery, via the cranial mesenteric artery, and via the cephalic vein. Distribution (liver, spleen, and lungs) was determined by computer-assisted external imaging techniques. On the average, after arterial infusion, 69.2% of the total activity was located in the liver, 3.6% in the spleen, 3.2% in the lungs, and 3.5% in the general circulation. Following venous injection, 50.7% of the radioactivity was found in the liver, 9.1% in the spleen, 8.6% in the lungs, and 6.7% in the peripheral blood. Once the liposomes entered the systemic circulation, they were cleared at the same rate (half-life beta = 21.5 hours) independent of their route of administration. Increased hepatic liposome uptake should translate into higher local and lower systemic liposomal drug levels.

Animals↗
PubMed1989

Hepatic arterial infusion of human recombinant tumor necrosis factor-alpha. An experimental study in dogs.

Local and systemic toxicities associated with hepatic arterial infusion of human recombinant tumor necrosis factor (rTNF) were studied in healthy adult mongrel dogs. The animals received saline containing human serum albumin with or without rTNF (0.02, 0.2, or 2.0 mg/m2). Arteriograms were made, and blood samples were collected for hematologic and biochemical analyses at regular intervals. The dogs were killed at 1, 3, and 7 days postinfusion and complete necropsies were performed. Specimens were obtained from various tissues for histopathologic evaluation. Results indicated that all but the highest dose of rTNF were well tolerated. Severe histopathologic changes were found in the liver, spleen, and kidneys of the animals receiving 2.0 mg/m2 rTNF. In addition, focal tubular degeneration was found in one dog administered 0.2 mg/m2 rTNF. These data suggest that the upper dose limit for hepatic arterial infusion of rTNF is between 0.2 and 2.0 mg/m2 and that renal function should be closely monitored after infusion.

Angiography↗
PubMed1989

A new device for transcatheter closure of the patent ductus arteriosus. A feasibility study in dogs.

A new device for transcatheter closure of the patent ductus arteriosus was developed and initially evaluated in the vasculature of adult mongrel dogs. The device consists of a nylon sack that can be made in various sizes and shapes. A small flexible crossbar attached to the distal end maintains the position of the sack while it is filled with a segment of modified guide wire. The device is delivered coaxially through a 10-Fr Teflon catheter and is easily repositioned or retrieved before release. The expansile force of the sack against the vessel wall can be varied, and its stability is easily checked prior to detachment. The device produced immediate and permanent vascular occlusion without inflammation or erosion. Over time, the entire unit became incorporated into the vessel wall by neointimal encasement. Nylon sacks offer a simple, unique method of closing virtually any ductus arteriosus without general anesthesia and major surgery.

Animals↗
PubMed1989

Percutaneously placed endovascular grafts for aortic aneurysms: feasibility study.

This limited study addressed the feasibility of treating aneurysms with a new transcatheter endoprosthesis. Aortic aneurysms were experimentally created in six dogs and subsequently bridged with nylon-covered, self-expanding metallic stents. The dogs were followed up for as long as 7 months (median, 22 weeks). In each dog, the graft effectively reconstituted the aortic lumen, excluding the aneurysm. One dog exhibited minimal (less than 1-mm) residual dilatation at the site of the aneurysm 7 months after graft placement. The nylon material acted as a support and template for neointimal encasement, enabling the formation of a new vascular lumen. It also remained porous at the origin of aortic side branches, preserving the visceral blood supply. One of the endovascular grafts failed to expand completely at its distal end, which promoted thrombus formation within the graft and resulted in the occlusion of both renal arteries. The dog was found comatose 48 hours after graft placement and was killed at that time.

Animals↗
PubMed1988

Self-expanding endovascular graft: an experimental study in dogs.

An arterial endovascular graft was constructed by wrapping an expandable nylon mesh around a framework of Gianturco self-expanding metallic stents. The devices were passed through a 12-French Teflon catheter and positioned in the normal abdominal aorta of five dogs, two of which also had a device placed in an external iliac artery. At follow-up (1-6 months), all grafts remained patent, even though slight luminal narrowing due to neointimal encasement was noted. Histologically, all grafts were covered by neointimal proliferation at the time of removal. The graft material expanded with the stents, resulting in a tight fit between the graft and the vessel wall. Side branches narrowed but remained open because of the size of the nylon mesh. No migration of the grafts equipped with a barbed lead stent was noted. Expandable nylon mesh can be used as an endovascular graft material when wrapped around a framework of self-expanding stents. The resulting device can be easily delivered via transcatheter techniques, and once placed in a vessel, the nylon acts as a support for neointimal encasement, which forms a new vascular lumen.

Animals↗
PubMed1988

Syndrome of diffuse abnormal insertional activity: case report and family study.

In 1979 Wiechers and Johnson described ten patients with diffuse abnormal insertional activity on EMG examination in the absence of neuromuscular disease. We present a family group with identical findings. The propositus is a 53-year-old woman who presented with back pain. EMG studies revealed trains of positive sharp waves with needle movement in all muscles studied. Nerve conduction studies, radiographs, and laboratory studies were all unremarkable. We recruited eight additional family members who underwent a screening EMG of five muscles. Four patients had trains of positive sharp waves present in all five muscles. To our knowledge, this is the first report confirming the findings of Wiechers and Johnson. We concur with them that the abnormality appears to be genetically transmitted in an autosomal dominant pattern. Although without clinical significance, it is important for electromyographers to be aware of this entity so as not to mistakenly ascribe serious neuromuscular disease to these patients.

Adolescent↗
PubMed1987

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↗
PubMed1987

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↗
PubMed1987

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↗
PubMed1987

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↗
PubMed1987

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↗