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Biomedical subjects

C Knutsen

Publications and source records attributed to C Knutsen.

7 recordsLinked to original sources
PubMed1989

Floxuridine-associated sclerosing cholangitis. A dog model.

The authors developed a dog model for the biliary sclerosis that occurs as a severe complication of protracted hepatic arterial floxuridine (FUDR) infusions (using implanted drug delivery systems) in patients with hepatic cancers. Infusaid pumps attached to hepatic arterial catheters were used for protracted infusions in ten mixed breed hounds. To allow repeated cholangiograms, the animals' gallbladders were removed and catheters connected to subcutaneous infusion ports were positioned in the cystic ducts. Five treated dogs received FUDR 0.3 mg/kg/day through the pump for a total of 30 days. Five control dogs received only saline through the pump. Cholangiograms were obtained before and after treatment in all animals. In the control group, serum liver function test results and the cholangiographic appearance of the biliary tree remained within normal limits. By contrast, in the FUDR-treated group, serum glutamic-pyruvic transaminase and alkaline phosphatase progressively rose above normal, starting 2-3 weeks into FUDR infusion, followed by hyperbilirubinemia (7-28 mg/dl peak levels) beginning 4 to 6 weeks after initiation of the drug infusion. Cholangiograms revealed focal strictures involving the central bile ducts (five dogs) and diffuse attenuation of the intrahepatic ducts (four dogs). Thus, the liver function abnormalities and the cholangiographic findings in this dog model mimic the hepatobiliary toxicity in sensitive patients receiving similar treatment.

Animals↗
PubMed1988

Effects of hepatic arterial yttrium 90 glass microspheres in dogs.

A 22-micron glass microsphere called TheraSphere (Theragenics Corp., Atlanta, GA) has been developed in which yttrium 89 oxide is incorporated into the glass matrix and is activated by neutron bombardment to form the beta-emitting isotope yttrium 90 (Y 90) before using the spheres as radiotherapeutic vehicles. The injection of up to 12 times (on a liver weight basis) the anticipated human dose of nonradioactive TheraSphere into the hepatic arteries of dogs was well tolerated and produced clinically silent alterations within centrolobular areas. The hepatic arterial (HA) injection of radioactive TheraSphere also produced portal changes similar to those observed in humans after external beam therapy. While the extent of damage increased with the delivered dose, radiation exposures in excess of 30,000 cGy did not cause total hepatic necrosis and were compatible with survival. No microspheres distributed to the bone marrow and absolutely no myelosuppression was encountered in any animal. Proposed hepatic exposures to humans of 5000 to 10,000 cGy by means of these microspheres, therefore, would appear to be feasible and tolerable. Radiotherapeutic microsphere administration preceded by regional infusion of a radiosensitizing agent and/or immediately following the redistribution of blood flow toward intrahepatic tumor by vasoactive agents can potentially yield a synergistic, highly selective attack on tumors confined to the liver.

Animals↗
PubMed1988

A simple method for long-term biliary access in large animals.

A simple method to obtain long-term access to the biliary tree in dogs and pigs is presented. In ten dogs and four pigs, a cholecystectomy was performed, the cystic duct isolated, and a catheter inserted into the cut end of the cystic duct. The catheter was connected to a subcutaneous infusion port, producing a closed, internal system to allow long-term access. The catheter placement was successful in three of the pigs and all of the dogs. Thirty-five cholangiograms were obtained in the 13 subjects by accessing the port with a 20 gauge Huber needle and injecting small amounts (4-10 mL) of contrast under fluoroscopic control. Cholangiograms were obtained up to four months after catheter placement without evidence for catheter failure or surgically induced changes in the biliary tree. This model provides a simple, reliable means to obtain serial cholangiograms in a research setting.

Animals↗