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Biomedical subjects

O Jurim

Publications and source records attributed to O Jurim.

At least 55 records · Page 3Linked to original sources

Transduction of hepatic allografts achieves local levels of viral IL-10 which suppress alloreactivity in vitro.

The application of gene therapy in transplantation might be targeted at immunoregulation within the donor graft. Viral IL-10 (vIL-10) down-regulates antigen presenting cells (APC) and effector functions in in vitro and in vivo models of alloreactivity. In the current study, we have constructed a replication-defective adenovirus bearing the cDNA encoding viral IL-10 and examined the level and chronicity of its expression in rat liver allografts up to 7 days after orthotopic transplantation. The results demonstrate that liver allografts may be efficiently transfected with adenovirus expressing viral IL-10. Detection of the recombinant viral cytokine was limited to the allograft without measurable levels in peripheral blood. In parallel, the effect of vIL-10 on mixed leukocyte reaction is also assessed using peripheral blood lymphocytes obtained from naive donor and recipient animals. Equivalent levels of viral IL-10 (5-10 ng/ml) achieved after adenovirus-mediated gene transfer suppress the in vitro alloreactivity of peripheral blood lymphocytes up to 70%. Adenovirus-mediated gene transfer of viral IL-10 offers the promise of effectively and favorably altering the alloreactive immune response.

Adenoviridae↗

Reduced-size grafts--the solution for hepatic artery thrombosis after pediatric liver transplantation?

Reduced-size liver grafts (RSG) were developed to alleviate the donor shortage for pediatric patients, particularly those requiring emergency transplantation. In theory, the large size of the hepatic artery available for anastomosis from RSG, as opposed to whole pediatric grafts, is less likely to lead to hepatic artery thrombosis (HAT). Therefore, the authors reviewed their experience with HAT, comparing RSG and whole-liver grafts in pediatric patients undergoing emergency liver transplantation. Despite the severity of illness of the recipients (UNOS status IV), and the intrinsic damage to the graft during reduction, HAT was not seen after RSG for emergency pediatric transplantation. In contrast, 29% of pediatric recipients who received whole grafts for emergency transplantation had HAT. RSG is a safe alternative to whole-liver grafts for pediatric liver transplantation, and may reduce the incidence of HAT.

Adolescent↗

Living-donor liver transplantation at UCLA.

BACKGROUND: Living-donor (LD) liver transplantation has been developed as an alternative to overcome the shortage of cadaver donor organs for pediatric recipients. PATIENTS AND METHODS: We reviewed our experience with 9 LD transplants performed between August 25, 1993 and August 3, 1994. The median recipient age and weight were 13 months and 10 kilograms. Left lateral segments from parental donors, with aortic inflow via saphenous vein grafts, were used in all cases. RESULTS: At a median follow-up of 160 days, all donors were alive and well. Recipient and graft survival were both 89%. Rates of hepatic artery thrombosis, portal vein thrombosis, biliary complications, and acute rejection were 22%, 11%, 11%, and 67%, respectively. CONCLUSIONS: Excellent outcome can be achieved with LD liver transplantation in small children with minimal donor risk. This procedure has the potential to emerge as the preferred treatment for pediatric liver transplant candidates for whom it is an option.

Adolescent↗

One thousand liver transplants. The lessons learned.

OBJECTIVE: To evaluate the first 1000 liver transplants performed at UCLA Medical Center to determine factors responsible for improved results. SUMMARY BACKGROUND DATA: Liver transplant has evolved impressively since the first case was performed in 1963. The 1980s have highlighted this progress with the development of better organ preservation, standardization of operative procedure, improved immunosuppressive agents, and better understanding of patient selection. METHODS: The first 100 consecutive liver transplants (group 1) performed from February 1984 through October 1986 were compared with the last 200 (group 2) performed between September 1991 and June 1992. An analysis was made of donor use; changes in patient candidacy; patient care variables; morbidity and mortality; survival data; and hospital resource use. RESULTS: In group 1, 31% of donors were refused because of medical unsuitability compared with 4% in group 2 (p < 0.0001). In group 1, alcoholic patients comprised 1% of liver transplant candidates compared with 20% group 2 (p < 0.0001). High-risk patients (United Network for Organ Sharing criteria 4) only comprised 11% of patients in group 1 compared with 37% in group 2 (p < 0.0001). Operative time (7.6 hours compared with 5.4 hours), packed cell replacement (17 units compared with 9.5 units), intensive care unit stay (10 days compared with 5 days), and hospital stay (50 days compared with 31 days) were all significantly improved (p < 0.05). In group 1, the 1-year survival rate was 73% and improved to 88% in group 2 (p < 0.0001). CONCLUSIONS: Despite unfavorable donor characteristics (obesity, cause of death, age, hypotension), most organs function well and should not be refused based on history alone. The older and high-risk patient (renal failure, ventilator dependence, portal vein pathology, and so on) is routinely transplanted with good success. Despite liberalization of both donor and recipient criteria, patient survival after liver transplant is improved, use of hospital resources is maximized, and cost reduction is achieved.

Adult↗

Regeneration-induced accelerated rejection in reduced-size liver grafts.

Liver regenerative processes are associated with enhanced expression of alloantigens. Accordingly, we tested the hypothesis that such enhanced surface expression of alloantigens during regeneration of reduced-size liver grafts is associated with accelerated rejection. Our OLT model was LEW (RT1) to BN (RT1n), with donor liver resected by 50%. The study group consisted of reduced-size allografts. Control groups were syngeneic reduced-size isografts and full-size allografts. Reduced-size isograft recipients survived indefinitely. Both isografts and allografts regenerated to their prereduction size within 12 days. Recipients of reduced-size allografts died of accelerated rejection within 12.2 +/- 0.8 days, significantly earlier than recipients receiving full-size allografts (36.2 +/- 4.1 days, P < 0.01). The accelerated rejection in the regenerating allografts was mediated both by cellular and humoral mechanisms, evidenced by earlier lymphocytic invasion of the graft, enhanced donor MHC class II expression, and the emergence of IgM antibodies, directed specifically against donor endothelial antigens. These data suggest that regeneration of reduced-size allografts is accompanied by accelerated cellularly and humorally mediated alloreactivity. Recipients of reduced-size allografts may, therefore, benefit from more potent immunosuppression during the period of active liver regeneration.

Animals↗

Role of 99mTc-labeled DISIDA scan in the assessment of marginal liver grafts after orthotopic transplantation.

Accurate prognostic indicators are lacking for livers with early marginal graft function, making the decision to re-transplant a difficult one. Therefore, we studied 99mTc-labeled DISIDA scanning as a predictor of recovery of marginal grafts. Records of 28 liver transplant recipients with prolonged periods of marginal graft function after liver transplantation were analyzed. Twelve of 28 (Group I) had delayed PNF and were re-transplanted within 3-8 days (mean 5.3) of surgery. The remaining 16 (Group II) recovered slowly, with normal graft function at 1 month. All patients received DISIDA scans 2 to 5 d after surgery. Clearance of tracer from the blood pool was slower in Group I patients (77S +/- 241 sec) than in Group II (260 +/- 38 sec; p < 0.01). Qualitative differences in the pattern of parenchymal uptake were also noted. Homogenous uptake, consistent with cholestasis, was seen in 15/16 (94%) Group II patients, with improved uptake after 7-35 d. In contrast, 11/12 Group I patients had non-homogenous uptake, consistent with multiple liver infarctions. This pattern correlated with higher peak SGOT in Group I (4358 +/- 658 U/dl vs 1636 +/- 127 U/dl p < 0.01), and PT (20 +/- 0.7 sec vs. 16.5 +/- 0.36 sec; p < 0.01). In summary, delays in DISIDA tracer clearance from blood, and non-homogenous hepatic uptake correlate with elevated liver function tests and with delayed PNF. Homogenous uptake correlates with graft recovery. DISIDA scans may, therefore, be useful in predicting recovery of marginal grafted livers.

Adult↗

Diagnosis and treatment of bowel perforation following pediatric orthotopic liver transplantation.

OBJECTIVE: Bowel perforation is a frequent cause of mortality after pediatric orthotopic liver transplantation. The aims of this study were to identify the cause of this phenomenon and to examine current methods of treatment. DESIGN: This is a retrospective analysis of 246 pediatric patients who underwent orthotopic liver transplantation at a large, urban, tertiary care medical center between 1984 and 1992. We examined the frequency of bowel perforations after transplantation and identified predisposing factors and signs. In this series, bowel perforations occurred in 24 of 246 recipients and were common in those who had previous liver-related surgery (22 patients). Clinical signs included fever (13 patients), leukocytosis (14 patients), and free air on abdominal roentgenograms (11 patients). RESULTS: Perforation occurred at the Roux-en-Y limb in 15 of 24 recipients as well as in the right transverse colon (five patients), terminal ileum (three patients), and duodenum (one patient). The repair was resection and/or primary closure (18 patients), or diversion (six patients). Recurrent perforations (nine patients) could not be attributed to the method of the repair. Perforation-related sepsis was the primary cause of death in 12 patients (50%) and was more common among patients who developed recurrent perforation (seven [78%] of nine patients). CONCLUSIONS: The occurrence and location of bowel perforation after pediatric orthotopic liver transplantation suggests that the cause is related to bowel injury during difficult hepatectomy. Mortality may be reduced by early second-look operations in high-risk patients.

Child↗

Celiac compression syndrome and liver transplantation.

OBJECTIVE: The authors assessed the prevalence and clinical significance of the celiac compression syndrome in liver transplantation patients. SUMMARY BACKGROUND DATA: Compression of the celiac axis by the median arcuate ligament of the diaphragm, causes a decrease in celiac artery blood flow which may lead to hepatic artery thrombosis in patients undergoing orthotopic liver transplantation. METHODS: From July 1991 to July 1992, 17 (10%) cases of celiac compression syndrome were identified among 164 consecutive adult patients who underwent liver transplantation. The diagnosis was confirmed by blood flow recording demonstrating a typical pattern of accentuated decrease in celiac blood flow during expiration. RESULTS: Surgical transection of the median arcuate ligament resulted in normalization of the hepatic artery blood flow. In two cases (11.7%), an interposition iliac graft from the recipient supra-celiac aorta was used for the arterial reconstruction. During the follow-up period of up to 15 months, there was no incidence of hepatic artery thrombosis. CONCLUSIONS: The clinical significance of the celiac compression syndrome is evident in liver transplantation in which the collateral circulation to the liver is compromised and the celiac artery remains the only source of arterial blood. It is imperative to identify and remove the obstruction of the celiac axis to prevent severe complications and potential graft loss.

Adult↗

Disseminated intravascular coagulopathy caused by acetic acid ingestion.

A case of disseminated intravascular coagulopathy following ingestion of 100% acetic acid is presented. The patient was successfully treated with fresh frozen plasma and cryoprecipitate. Complete resolution of the bleeding diathesis and the disturbed coagulation tests was achieved.

Acetates↗