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Biomedical subjects

K C Wright

Publications and source records attributed to K C Wright.

At least 73 records · Page 4Linked to original sources

Expandable biliary endoprosthesis: an experimental study.

Expandable stents constructed of stainless-steel wire were inserted in the extrahepatic bile ducts of five animals to determine the effect of the endoprosthesis on the ductal wall. The stents were left in place 4-23 weeks, at which time the bile ducts were inspected. The bile ducts remained patent in all animals. Relatively mild reactive inflammatory changes observed in the wall of the bile ducts were more pronounced in animals with stents in place for the longest periods. A relatively small-caliber catheter (9 French) was necessary for the introduction of the stent, which acquired a much larger diameter once it was released from the catheter. This study suggests that expandable wire stents could be safely used to relieve biliary obstruction.

Animals↗

Regional isolation-perfusion: an experimental percutaneous approach tested and compared with arterial occlusion-infusion.

A percutaneous approach was developed for the performance of regional isolation-perfusion, a surgical chemotherapeutic procedure for the intraarterial treatment of neoplasms. This technique was compared with percutaneous transcatheter arterial occlusion-infusion concerning local and systemic drug levels. Floxuridine (FUDR) was administered into a femoral artery of adult mongrel dogs, first by arterial occlusion-infusion, and 4 weeks later by regional isolation-perfusion of the opposite hind limb. Local and systemic plasma samples and local muscle specimens were collected for determination of FUDR levels. Results indicated not only that regional isolation-perfusion could be accomplished percutaneously, using balloon catheters, but also that the technique produced significantly greater local tissue FUDR levels (P less than 0.05) than those achieved with arterial occlusion-infusion.

Angioplasty, Balloon↗

Percutaneous transcatheter filter for the inferior vena cava. A new device for treatment of patients with pulmonary embolism.

A filter for the inferior vena cava has been devised for treatment of pulmonary embolism. Percutaneous insertion of the filter is accomplished with the use of a sheath and an 8-F catheter. Therapeutic results involving 28 patients have been excellent. No embolism has recurred; no vena cava thrombosis has developed. Since minor surgery is unnecessary, the procedure saves time and is cost-effective.

Animals↗

Experimental evaluation of intraarterial occlusion-infusion chemotherapy.

Intraarterial occlusion-infusion of vincristine and Adriamycin was performed in six dogs using balloon infusion catheters. Tissue toxicity was compared with that obtained when the same drugs were administered by simple arterial infusion. Balloon occlusion of the external iliac artery produced reversed blood flow in the deep femoral, caudal femoral, and superficial circumflex iliac arteries, potentially altering the distribution of the drugs. Thrombosis of arterial branches occurred in three dogs, sooner but no more often in the groups receiving occlusion-infusion chemotherapy. Skin ulceration and dilatation of peripheral small vessels were significantly more frequent and extensive in the groups receiving occlusion-infusion. One infusion dog developed a single small ulcer on the hind paw; five of the six occlusion-infusion dogs developed multiple skin ulcers on the thigh and/or distal extremity. These findings suggest that even though intraarterial occlusion-infusion chemotherapy is not applicable in all instances, the technique does produce significantly greater drug-related effects than simple intraarterial infusion.

Animals↗

Experimental percutaneous renal embolization using BCG-saturated gelfoam.

Adult mongrel dogs (20-25 kg) were used to evaluate the administration of Bacillus Calmette-Guerin (BCG) in conjunction with total renal embolization for possible application in the management of metastatic renal cell carcinoma (RCC). Kidneys were surgically removed at 1, 2, and 3 weeks postembolization, examined grossly and microscopically, and then compared with kidneys embolized in the same manner without BCG. The procedure stimulated the reticuloendothelial system more than did renal embolization alone, and although a high dose (6 X 10(8) organisms) of BCG was administered, no complications were encountered. These results warrant a clinical trial of this technique in patients with advanced RCC.

Adenocarcinoma↗

Partial splenic embolization using polyvinyl alcohol foam, dextran, polystyrene, or silicone. An experimental study in dogs.

Partial splenic arterial embolization (50% reduction in flow) was evaluated in dogs using polyvinyl alcohol foam or microspheres (20-500 mu) made of dextran, polystyrene, or silicone. Dextran and polystyrene were found to be superior for several reasons: they were easier to use, did not shatter when agitated, and produced permanent, homogeneous, peripheral occlusion with only one administration. Partial embolization with dextran or polystyrene increased platelet levels within 1 week and markedly reduced splenic size with minimal if any collateral filling within 6 weeks. Microscopically, no acute infarction or necrosis was seen at 6 weeks; there was some fibrosis, but the remaining parenchyma appeared normal.

Animals↗

The effects of prostacyclin (PGI2) on prolactin secretion in vitro.

Continuously superfused rat anterior pituitary cells were used to study the effects of exogenous prostaglandins (PGs) and thromboxanes (TXs) on the secretion of prolactin (PRL). No change in hormone release was observed upon superfusion with TXB2 (10(-5)M) or the TX synthesis inhibitor, imidazole (1.5 mM). PGs A2, B2, D2, E1, E2, F1 alpha, F2 alpha, and endoperoxide analogs, U-44069 and U-46619, also had no effect on PRL secretion (all at 10(-5)M). In contrast 10(-5)M PGI2 was repeatedly found to stimulate PRL release to a level at least 125% above control, while producing no apparent change in the amount of hormone secreted in response to TRH. Somatostatin (SRIF), at a dose of 10(-6)M, maximally inhibited TRH-induced PRL output, but failed to alter the PRL response to PGI2. These studies indicate that PGI2 may have a direct effect on the anterior pituitary to modify PRL secretion.

Animals↗

Dynamics and regulation of TSH secretion by superfused anterior pituitary cells.

Superfused dispersed cells respond rapidly to 2- to 10-min pulses of TRH (10(-10) to 10(-7) M) in a dose-dependent manner. The effects of decreasing the stimulus duration can be overcome by a proportional increase in concentration of TRH. A TRH stimulus of 10 min or greater duration results in a sharp peak in TSH secretion followed by a lower plateau. Somatostatin (10(-8) M inhibits the response to TRH (t X 10(-9) M). T3 (2.0 microgram/dl) inhibits TRH-induced TSH secretion by superfused pituitary fragments, but not by dispersed cells. Corticosterone (50 microgram/dl), however, inhibits crude CRF-induced ACTH secretion by such cells.

Adrenal Glands↗

Effects of various prostanoids on thyrotropin secretion by superfused anterior pituitary cells.

Continuously superfused rat anterior pituitary cells were used to study the effects of prostaglandins (PGs) and a thromboxane (TX) on the secretion of TSH. Indomethacin, a blocker of PG synthetase, inhibited the amount of TSH secreted in response to TRH. This reduction in TRH responsiveness was overcome by administration of PGE2 in combination with the TRH. Arachidonic acid, a prostanoid precursor, increased the amount of TSH released by TRH. Superfusion with TXB2 or imadazole, an inhibitor of TX synthetase, did not change TSH secretion. PGs A2, B2, D2, F1 alpha, F2 alpha, and endoperoxide analogs U-44069 and U-46619 had no effect on hormone release. PGE1 and E2 both increased TRH-stimulated TSH, but neither compound affected basal output; PGI2 was found to stimulate TSH release. Somatostatin inhibited TRH-induced TSH, but failed to block the effects of the PGs. These studies demonstrate that PGs, but no TXs, play a role in TSH secretion. PGE1 and PGE2 appear to modulate TRH responsiveness, while PGI2 directly stimulates hormone output.

Animals↗

Factors modulating the secretion of thyrotropin and other hormones of the thyroid axis.

The first portion of this paper is devoted to an overview of the normal function of the hypothalamo-pituitary-thyroid axis. This section emphasizes areas of current research interest and it identifies several sites and mechanisms that are potentially important interfaces with toxins or toxic mechanisms. We then describe an in vitro technique for the continuous superfusion of enzymatically dispersed pituitary cells; this approach is particularly valuable in studying the dynamics of the TSH responses to the factors known (or suspected) to regulate TSH secretion in vivo. Using this technique, we have found that 10(-5)M prostaglandin (PG)I2 stimulates TSH secretion without altering the response to TRH (10(-8)M), and that this stimulation is not due to its rapid conversion to 6-keto PGF1 alpha. In contrast PGs of the E series (PGE1 and PGE2, 10(-5)M) increase responsiveness to TRH but have no effect alone. We found no effects of any of the other prostanoids tested (PGs A2, B2, F1 alpha, F2 alpha, thromboxanes A2 and B2, and the endoperoxide analog, U-44069. Somatostain (10(-9)M inhibits TRH-induced TSH secretion, but does not alter the responsiveness to PGI2. These findings suggest that somatostatin blocks TSH secretion at a point that is functionally prior to the involvement of the PGs, and perhaps does so by blocking synthesis or limiting availability of selected PGs.

Animals↗

Pharmacological studies of the involvement of hypothalamic prostaglandins in the regulation of thyrotropin secretion.

A case is made for the involvement of pituitary prostaglandins (PGs) in the regulation of thyrotropin (TSH) secretion by citing recent evidence that TSH release in vivo and in vitro is enhanced by treatment with exogenous PGs and is inhibited by drugs (e.g., indomethacin) that block PG synthesis. Pharmacological studies were then performed to test the hypothesis that hypothalamic PGs also affect TSH secretion indirectly via the appropriate hypothalamic hormones that regulate pituitary secretion. The inhibition of thyroidectomy-induced TSH secretion was used as an endpoint in choosing the best of several drugs purported to inhibit PG synthesis. The established effectiveness of indomethacin and aspirin were used for reference in testing the following drugs: naproxen, mefenamic acid, tranylcypromine, and phenelzine. Only naproxen was found to be effective, but since it was no more potent than indomethacin, the latter drug was used for subsequent work. Indomethacin was stereotaxically implanted into several hypothalamic regions known to regulate TSH secretion, and sequential plasma samples were analyzed for TSH by radioimmunoassay. Bilateral implants of indomethacin in the anterior hypothalamic area increased TSH secretion throughout the 72 hr period of study. Sham inplants at this site and indomethacin implants in other nearby sites were ineffective. These findings suggest that endogenous PGs play an inhibitory role in the hypothalamic regulation of pituitary secretion.

Animals↗

Experimental evaluation of ethanol-ethiodol for transcatheter renal embolization.

Adult mongrel dogs were used to evaluate and compare the use of ethanol and ethanol-Ethiodol for transcatheter renal arterial embolization. Each agent was administered into a main renal artery in five dogs and evaluated with regard to ease of use, radiopacity, arterial occlusion, parenchymal damage, and toxicity. Both agents were easy to inject, and no complications were encountered in any of the animals. Ethiodol added the ability to fluoroscopically monitor the infusate for reflux and distribution, yielded a more homogeneous distribution of the ethanol within the renal vasculature, and increased the embolic effects of the ethanol. Adding Ethiodol to ethanol should decrease the latter's complications since administration can be monitored fluoroscopically and a smaller volume of ethanol could perhaps be used to achieve the desired result. Additional research is needed to determine the safety of administering larger volumes of Ethiodol into the renal artery.

Animals↗

Occlusive effect of metallic stents on canine ureters.

A three-part study, with successive modifications based on preceding results, was conducted to evaluate ureteral placement of metallic stents. Gianturco self-expanding (10 mm and 4 mm diameter) and balloon-expanded (4 mm diameter) metallic stents were placed in normal and stenotic canine ureters. No migration or ureteral perforation occurred during the follow-up of 10 mm stents. Varying degrees of hydronephrosis and hydroureter were found on all 1-week pyelograms. At 4 weeks, complete occlusion of the stented ureter was noted in all cases because of mucosal hyperplasia around the stent wires. To prevent this reaction, 4 mm self-expanding stents constructed of smaller wire that was uncoated or coated with either Teflon or poly-urethane were tested in five dogs. In all cases, results were similar to those obtained with the larger prostheses. Finally, 4 mm balloon-expanded stents were placed in a normal ureter of three dogs. In one dog, the stent migrated out of the ureter. No migration or ureteral perforation occurred in the two remaining dogs. In these animals, mucosal hyperplasia and complete ureteral occlusion occurred 6 and 8 weeks after placement. Therefore, ureteral placement of Gianturco self-expanding as well as balloon-expanded metallic stents leads to occlusion of the ureter instead of maintaining its patency. Stents, therefore, may be useful as ureteral occlusion devices.

Animals↗

Monodisk: device for percutaneous transcatheter closure of cardiac septal defects.

The Monodisk, a device to facilitate percutaneous closure of cardiac septal defects, was developed and tested in vitro and in vivo. Atrial septal defects (8-10 mm) were created in five dogs using transcatheter techniques. The defects were then closed with the Monodisk. The device was easily and successfully fixed in place in all dogs. The efficacy of the device was determined radiographically. No shunting of contrast medium was observed in any case. Animals were followed for 6 months. Results showed good biocompatibility and several advantages of the device: it requires only a simple one-step placement procedure; it utilizes a small delivery system; it is easy to place and detach; it is self-centering and stable; and it can be repositioned or retrieved prior to detachment. Its possible clinical applications include correction of atrial septal defects, ventricular septal defects, patent ductus arteriosus, as well as creating an aortopulmonary window.

Animals↗

Treatment of experimentally induced atherosclerosis in swine iliac arteries: a comparison of self-expanding and balloon-expanded stents.

Atherosclerosis was induced in 20 Hanford miniature swine. Subsequently, one iliac artery lesion in each of 16 pigs was stented with either a self-expanding (8 pigs) or a balloon-expanded (8 pigs) stent. Immediately after stent placement, 4 animals in each group were taken off the atherogenic diet and continued on normal chow for the remainder of the study. Four months after stents were placed, atherosclerosis and the mural changes associated with the stent were more clearly evident in the arteries of the pigs continued on the atherogenic diet. These pigs also exhibited significantly more neointimal proliferation. In addition, the arteries containing the balloon-expanded stents showed more extensive and complex intimal changes when compared with arteries with self-expanding stents. Although both stent designs were equally effective in maintaining vascular patency, the balloon-expanded stent was more traumatic to the vessel wall which resulted in a significantly greater neointimal thickness.

Animals↗