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Timothy C McCowan

Publications and source records attributed to Timothy C McCowan.

13 recordsLinked to original sources
PubMed2003

Route of hepatocyte delivery affects hepatocyte engraftment in the spleen.

In laboratory animals, intrasplenic hepatocyte transplantation corrects the physiologic abnormalities associated with decompensated liver disease. The clinical experience with hepatocyte transplantation for cirrhosis has been disappointing when compared with laboratory experience. The route of hepatocyte delivery may influence hepatocyte engraftment and function. Outbred pigs were recipients of allogeneic pig hepatocytes. Donor hepatocytes were isolated by collagenase perfusion and labeled using 5(6)-carboxyfluorescein diacetate succinimidyl-ester (CMFSE). Cells were introduced into pig spleens by infusion through the splenic artery or by direct splenic puncture. Direct intrasplenic injection produced engraftment that was far superior to that obtained using splenic artery infusion. Splenic artery infusion produced a gastric erosion and large areas of splenic necrosis secondary to vascular occlusion with hepatocytes, whereas direct splenic injection was associated with clinically insignificant intraabdominal hemorrhage. The route of hepatocyte delivery may influence hepatocyte engraftment and explain the disparity in efficacy of hepatocyte transplantation between the laboratory and clinic.

Animals↗
PubMed2003

Microbubble-augmented ultrasound declotting of thrombosed arteriovenous dialysis grafts in dogs.

PURPOSE: Transcutaneous low-frequency ultrasound (LFUS) can effectively lyse clots in the presence of microbubbles. This study was designed to test the commercially available human albumin microspheres injectable suspension octafluoropropane formulation, Optison, to establish efficacy and assess US parameters of intensity and wave modes in a canine model of a thrombosed arteriovenous (dialysis) graft. MATERIALS AND METHODS: Arteriovenous grafts in five dogs were cannulated, temporarily ligated, and thrombosed. Different declotting techniques were randomized to treat nine groups. Control groups involved direct saline (4.5 mL) clot injection in 0.5-1.0-mL increments. One group underwent peripheral intravenous microbubble injection (13.5 mL). Six groups underwent direct incremental clot injection of 4.5 mL of microspheres with LFUS for 30 minutes in 3-5-minute increments with use of various intensity settings in continuous-wave and pulsed-wave (PW) modes. At each increment, angiography was used to grade flow, declotting, and overall success. RESULTS: One hundred four procedures showed success in all 24 high-intensity PW modes (1.2-2.0 W/cm(2)); only one of 20 control experiments was successful (P <.0001). Medium-intensity modes yielded intermediate success rates. Lowest-intensity direct-injection groups and intravenous and control groups ranked lower. Results at 30 minutes were better than at 15 minutes (P <.0001). CONCLUSIONS: LFUS with direct injection of microbubbles is effective in lysing moderate-sized clots and recanalizing thrombosed arteriovenous grafts. It best succeeds at the higher range of intensity settings tested in PW mode. Further development is justified.

Albumins↗
PubMed2003

Isolated hepatocyte transplantation in an infant with a severe urea cycle disorder.

OBJECTIVE: Transplantation of isolated hepatocytes in animal models has been shown to correct inborn errors of metabolism. Based on these studies and our experience with hepatocyte transplantation in a child with Crigler-Najjar syndrome, isolated hepatocyte transplantation was performed to attempt metabolic reconstitution in a male infant with severe ornithine transcarbamylase (OTC) deficiency. METHODS: An infant with an antenatal diagnosis of OTC deficiency was managed intensively to prevent hyperammonemia. Isolated hepatocytes were obtained by collagenase perfusion of donated livers not used for transplantation. Hepatocytes were infused in batches over the first 4 weeks of life via an umbilical venous catheter positioned in the portal vein. Immunosuppression consisted of tacrolimus and corticosteroids. RESULTS: Over 4 billion viable hepatocytes were transplanted during the first 3.5 weeks of life. A period of metabolic stability was achieved between days 20 and 31 during which normal protein intake was tolerated while phenylbutyrate was weaned. During this time, plasma ammonia and glutamine remained within normal limits. Hyperammonemia reappeared abruptly on day 31 of life. Protein tolerance diminished to baseline; metabolic stability was subsequently reattained only following successful liver transplantation at 6 months of age. CONCLUSIONS: Isolated hepatocyte transplantation appeared to result in temporary relief of hyperammonemia and protein intolerance attributable to OTC deficiency. The metabolic stability achieved was lost after 11 days presumably because of rejection of the transplanted cells because of insufficient immunosuppression. Future attempts at isolated hepatocyte transplantation for inborn errors of metabolism in humans should include adequate immunosuppression and a liver biopsy as a means of proving hepatocyte engraftment and function.

Adult↗
PubMedDate not supplied

Paravertebral block: an improved method of pain control in percutaneous transhepatic biliary drainage.

BACKGROUND AND PURPOSE: Percutaneous transhepatic biliary drainage remains a painful procedure in many cases despite the routine use of large amounts of intravenous sedation. We present a feasibility study of thoracic paravertebral blocks in an effort to reduce pain during and following the procedure and reduce requirements for intravenous sedation. METHODS: Ten consecutive patients undergoing biliary drainage procedures received fluoroscopically guided paravertebral blocks and then had supplemental intravenous sedation as required to maintain patient comfort. Levels T8-T9 and T9-T10 on the right were targeted with 10-20 ml of 0.5% bupivacaine. Sedation requirements and pain levels were recorded. RESULTS: Ten biliary drainage procedures in 8 patients were performed for malignancy in 8 cases and for stones in 2. The mean midazolam use was 1.13 mg i.v., and the mean fentanyl requirement was 60.0 microg i.v. in the block patients. Two episodes of hypotension, which responded promptly to volume replacement, may have been related to the block. No serious complications were encountered. The mean pain score when traversing the chest wall, liver capsule, and upon entering the bile ducts was 0.1 on a scale of 0 to 10, with 1 patient reporting a pain level of 1 and 9 reporting 0. The mean peak pain score, encountered when manipulating at the common bile duct level or when addressing stones there, was 5.4 and ranged from 0 to 10. CONCLUSIONS: Thoracic paravertebral block with intravenous sedation supplementation appears to be a feasible method of pain control during biliary interventions.

Adult↗
PubMedDate not supplied

Popliteal artery disease: diagnosis and treatment.

The popliteal artery is a relatively short vascular segment but is affected by a unique set of pathologic conditions. These conditions, which may be common throughout the arterial system or exclusive to the popliteal artery, include atherosclerosis, popliteal artery aneurysm, arterial embolus, trauma, popliteal artery entrapment syndrome, and cystic adventitial disease. The clinical manifestations, imaging appearances, and treatment options associated with these pathologic conditions differ significantly. Consequently, the radiologist should be familiar with these conditions to direct imaging for accurate diagnosis and treatment and to prevent loss of limb.

Adolescent↗