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Biomedical subjects

S Todo

Publications and source records attributed to S Todo.

At least 343 records · Page 19Linked to original sources

Conversion of liver allograft recipients from cyclosporine to FK506 immunosuppressive therapy--a clinicopathologic study of 96 patients.

The effect of conversion from cyclosporine-steroid immunosuppression to the new agent FK506 was studied in 96 liver allograft recipients who were experiencing graft dysfunction or cyclosporine toxicity. Patients were stratified according to the cause of graft dysfunction that ultimately led to conversion to FK506. Response to FK506 introduction was monitored pathologically and biochemically. The outcome of a switch from CsA to FK506 was highly favorable in patients experiencing acute and the early stages of chronic rejection, despite optimal conventional therapy. Patients with later stages of chronic rejection did not respond to conversion to FK506 and most eventually lost their liver grafts in this process. Patients in whom we had difficulty separating chronic rejection from chronic persistent or low-grade chronic active hepatitis were mostly unaffected by conversion to FK506. Active hepatitis was a poor indication for conversion, because most of the patients experienced graft failure or died from liver failure. As a group, there was no statistically significant change in renal function 180 days after conversion to FK506. These findings expand the experience with FK506 in human liver allograft recipients.

Adolescent↗

Hepatic artery pseudoaneurysm ligation after orthotopic liver transplantation--a report of 7 cases.

Pseudoaneurysm (PA) is a rare but life-threatening complication of liver transplantation. The authors present their experience on 7 patients treated by ligation of a post-OLT PA. Hepatic artery ligation or embolization was performed from 10 to 70 days after liver transplantation. Of the seven patients, four survived, one developed a biliary stricture, treated by percutaneous balloon dilatation, two died of a complication not related to treatment, and one died of multiple organ failure.

Adult↗

[Recombinant human granulocyte-colony stimulating factor (rhG-CSF) treatment for spleen abscess and periostitis in a patient with chronic granulomatous disease].

A 9-year-old boy with chronic granulomatous disease was hospitalized on May, 1991, because of continued fever and pain in the right elbow. Increased bone intensity at the distal end of right humerus on x-ray and a 33 x 36 mm space-occupying lesion in the spleen on abdominal CT scan were recognized. Under a diagnosis of periosteitis and spleen abscess, intravenous infusion of rhG-CSF at a dose of 200 micrograms/m2/day was started in combination with antimicrobial therapy. Fever, tenderness, swelling in the right elbow and inflammatory indices improved three weeks after the institution of therapy. Hydrogen peroxide (H2O2) formation by neutrophil increased significantly, although intermittently, during the therapy. The spleen abscess had completely vanished on CT scan on February, 1992. The therapy was well tolerated and no significant side effects were observed. The use of rhG-CSF in combination with potent antibiotics is recommended for patients with serious infections in chronic granulomatous disease to avoid a fatal course.

Abscess↗

Stability and sorption of FK 506 in 5% dextrose injection and 0.9% sodium chloride injection in glass, polyvinyl chloride, and polyolefin containers.

The effects of the diluent, the storage container, light, and infusion through various types of tubing on the stability and sorption of FK 506 were studied. Solutions of FK 506 in 0.9% sodium chloride injection or 5% dextrose injection were stored at room temperature (24 +/- 2 degrees C) in glass i.v. bottles, polyvinyl chloride (PVC) minibags, and polyolefin containers. FK 506 solution in 0.9% sodium chloride injection was stored in plastic syringes at room temperature and either exposed to normal room light or stored in the dark. FK 506 solution in 5% dextrose injection was placed in plastic syringes and infused through PVC anesthesia extension tubing, PVC i.v. administration set tubing, and fat emulsion tubing over a two-hour period. The infused samples and samples collected from the containers and syringes at intervals up to 48 hours were analyzed for FK 506 concentration by high-performance liquid chromatography. FK 506 concentrations remained greater than 90% of initial concentration for admixtures in 5% dextrose injection stored in glass bottles for 48 hours and for admixtures in 5% dextrose injection or 0.9% sodium chloride injection stored in polyolefin containers for 48 hours. No change in concentration was measured for admixtures in 0.9% sodium chloride injection stored in plastic syringes, and exposure to light did not affect the stability of FK 506 solution. No substantial change in concentration occurred in FK 506 solution in 5% dextrose injection infused through PVC anesthesia extension tubing, PVC i.v. administration set tubing, or fat emulsion tubing. FK 506 admixtures prepared with 5% dextrose injection or 0.9% sodium chloride injection should be stored in polyolefin containers. If polyolefin containers are not available, solutions should be prepared with 5% dextrose injection and stored in glass bottles.

Adsorption↗

Tacrolimus (FK 506)--a new therapeutic agent for severe recalcitrant psoriasis.

BACKGROUND: Psoriasis, a disease of unknown etiology, is in some patients severe, extremely debilitating, and unresponsive to conventional therapies, including UV-B, oral psoralen with long-wave UV radiation in the A range (PUVA), oral retinoids, and methotrexate. We report the results from our study of seven patients with refractory psoriasis who were treated with the new immunosuppressive drug, tacrolimus (FK 506). OBSERVATIONS: All seven patients showed a dramatic resolution of psoriasis that remained in remission as long as they received full-dose therapy. Serial skin biopsy specimens demonstrated a rapid disappearance of the inflammatory infiltrate and a slower resolution of the epidermal changes. Tacrolimus was well tolerated during the 5.5 to 14 months of observation. Side effects, including nephrotoxicity and hypertension, were controlled by appropriate modification of drug dosage. CONCLUSIONS: Tacrolimus, a new immunosuppressive agent, is effective in treating patients with severe recalcitrant psoriasis. The mechanism of its action in psoriasis is unknown, but it may be related to its ability to modulate immune function. Further studies will establish criteria for patient selection and drug dosage, to maximize efficacy of this agent in psoriasis, while minimizing its toxicity.

Administration, Oral↗

[Clinical experience with FK 506].

FK 506 is a superior immunosuppressive agent that should improve patient survival after the commonly performed transplant procedures, make feasible transplantations that have been previously impractical, allow immune intervention for serious autoimmune diseases, and create a better spin-off understanding of basic biologic processes including signal transduction.

Autoimmune Diseases↗

Replacement of donor lymphoid tissue in small-bowel transplants.

The presence of recipient lymphocytes in grafts is thought to equate with rejection. Thus, we wished to follow the fate of lymphocytes after transplant of the small bowel. Three complete small-bowel transplants, two with the liver from the same donor also transplanted, were done successfully. Patients were immunosuppressed with FK 506. 5 to 11% of lymphocytes in the recipients' peripheral blood were of donor origin during the early postoperative period when there were no clinical signs of graft-versus-host disease. However, donor cells were no longer detectable after 12 to 54 days. Serial biopsy specimens of the grafted small bowel showed progressive replacement of lymphocytes in the lamina propria by those of the recipient's HLA phenotype. Lymphoid repopulation was complete after 10 to 12 weeks but the epithelial cells of the intestine remained those of the donor. The patients are on enteral alimentation after 5, 6, and 8 months with histopathologically normal or nearly normal intestines. Re-examination of assumptions about the rejection of intestinal grafts and strategies for its prevention are required following these observations.

Anti-Bacterial Agents↗

Studies on mechanisms of augmentation of liver regeneration by cyclosporine and FK 506.

Evidence could not be found of immune modulation of liver regeneration. The powerful immunosuppressive drug FK 506, which augments the response after partial hepatectomy in normal rats, had the same effect in T cell-deficient nude rats. The cytotoxicity of natural killer cells in treated nude rats was not significantly changed by FK 506 therapy. However, the serum of FK 506-treated nude rats increased hepatocyte proliferation when added to third-party hepatocyte cultures, suggesting that FK 506 had induced a serum growth factor in the nude rats or had suppressed an inhibitory factor. A hypothesis was advanced that FK 506 (and cyclosporine) affects hepatic growth by nonimmunological pathways.

Animals↗