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Biomedical subjects

A G Tzakis

Publications and source records attributed to A G Tzakis.

At least 19 recordsLinked to original sources
PubMed2003

Ten years of sirolimus therapy in orthotopic liver transplant recipients.

BACKGROUND: Sirolimus therapy has been used in orthotopic liver transplant (OLT) recipients diagnosed with a variety of diseases; chronic graft rejection (CR), calcineurin associated renal toxicity, preemptive immune suppression, calcineurin related neurotoxicity, preemptive therapy in transplant recipients with history of hepatocellular carcinoma, and steroid resistant allograft rejection. METHODS: A search for the medical literature and experiences involving sirolimus was done. RESULTS: Several animal and human reports evaluating the use sirolimus in liver transplant recipients are found and discussed. CONCLUSION: Sirolimus has been used for multitude of indications, primarily based on anecdotal experiences. However, reports of sirolimus related side effects have decreased the transplant communities' enthusiasm towards promoting this agent as a safe immune suppression agent.

Creatinine↗
PubMed2003

Intestinal transplantation: advances in immunosuppression and surgical techniques.

Campath-1H is being used as induction immunosuppression for intestinal/multivisceral transplantation. Patient and graft survival in this preliminary experience is similar to previous studies but there has been a significant decrease in the incidence and severity of acute rejections without increase of opportunistic infections. Collage of the abdominal wall (transplantation of a composite graft of the abdominal wall) can provide biologic coverage of the newly transplanted abdominal organs if necessary. Partial abdominal exenteration, ex vivo resection, and intestinal autotransplantation may be useful in removing otherwise unresectable lesions of the root of the mesentery.

Graft Rejection↗
PubMed2001

Liver transplantation for factor VII deficiency.

Factor VII deficiency is a serious, potentially lethal disorder of blood coagulation caused by a defect in hepatic factor VII synthesis. We report two children, sisters, both with severe, recurrent hemorrhagic complications from factor VII deficiency, successfully treated with orthotopic liver transplantation. Postoperatively, they remain symptom free with normal coagulation profiles.

Child↗
PubMed2001

Serum citrulline and rejection in small bowel transplantation: a preliminary report.

BACKGROUND: There is no known serum marker for intestinal rejection. Serum concentrations of the amino acid citrulline arise almost exclusively from the intestinal mucosa. We examined the impact of acute cellular rejection (ACR) of intestinal allografts on serum citrulline levels. METHODS: Citrulline concentrations were assayed in serum samples of healthy volunteers (n=6) and seven patients who underwent small bowel transplants (SBTx). Trends in mean citrulline concentrations versus degree of ACR were assessed by matching posttransplantation citrulline concentrations with patients' grade of ACR at time of serum collection. Rejection was confirmed by biopsy and graded by following standardized criteria. An additional patient had citrulline concentrations determined for 31 sequential specimens 3-60 days posttransplant. RESULTS: Mean citrulline concentrations in controls were significantly higher than posttransplantation samples at any rejection grade. Mean concentrations declined significantly as rejection severity increased. The overall downward trend was statistically significant (P<0.05). In sequential measurements, citrulline levels increased significantly over time with declining severity of rejection. The increase in mean citrulline concentration between posttransplant days 3-16 and 52-60 was significant (P<0.01). CONCLUSIONS: Serum citrulline levels decline with increasing grade of ACR and may be a useful serum marker for intestinal rejection.

Adult↗
PubMed2001

Donor and recipient pretransplant conditioning with nonlethal radiation and antilymphocyte serum improves the graft survival in a rat small bowel transplant model.

BACKGROUND: Lymphoid tissue within the intestinal graft require immunomodulatory strategies to prevent graft versus host disease (GVHD) after transplant. Herein, we evaluate the potential advantage of donor-specific bone marrow infusions in donor and or recipient preconditioned with total body irradiation and or antilymphocyte serum (ALS) on the incidence of GVHD and rejection after small bowel transplantation. METHODS: Heterotopic SBTx was performed from DA to Lewis rats and distributed in nine groups: control group G0 (n=4) and G1 (n=6) without irradiation; recipients in G2 (n=4) were given 400 rd although in groups 3 (n=5), G4 (n=6), G6 (n=5), G7 (n=5), and G8 (n=6) with 250 rd. Donors in G5 (n=4) and G6 were given 250 rd of total body irradiation 2 hours before intestinal retrieval. Donors and recipients in G7 and donors in G8 additionally received ALS (day -5). G1, 2, 3, 5, 6, 7, and 8 were infused with UDBM and G4 with the same amount of TCDBM. Animals received tacrolimus for 15 days and accessed for rejection, GVHD and for chimerism analysis. RESULTS: High mortality due to GVHD was observed in G2, 3, and 4, and correlated with high levels of donor T cells in recipients blood. G0 and G1 showed early acute rejection with progression toward chronic rejection, in contrast to the preconditioned groups. High and low doses of total body irradiation resulted in allogeneic and in a mixed chimerism, respectively. Decrease in donor chimeric cells after 11 weeks in preconditioned groups was correlated with severe allograft rejection. CONCLUSION: Donor preconditioning with 250 rd and or ALS combined with recipient preconditioning and donor-specific bone marrow infusions prevented GVHD and resulted in a transient mixed chimerism with inhibition of allograft rejection after small bowel transplantation.

Animals↗
PubMed2001

Apoptosis and rejection in rat intestinal transplantation: correlation with FK506 doses and donor specific bone marrow infusions.

BACKGROUND: Our purpose was to investigate the occurrence and the evolution of apoptosis of enterocytes during acute and chronic rejection in an experimental model of allogeneic heterotopic small bowel transplantation (SBTx). METHODS: Forty-five rats were divided in 10 experimental groups according to the dose of FK506 administration and donor bone marrow infusions (DBMI). Groups 1 and 2 did not received BMI. Groups 3 and 4 received 150x106 cells at day 0, groups 5 and 6 received 75x106 cells at days 0-4, groups 7 and 8 received 75x106 cells at days 4 and 10, and groups 9 and 10 received 30x106 cells at days 4, 10, 15, 20, and 25. Animals of groups 1, 3, 5, 7, and 9 were immunosuppressed with 0.5 mg/kg FK 506, although the remaining groups with 1 mg/kg FK 506, from day 0 to 4 after transplant. Fragment end labeling of DNA was used to detect apoptosis. RESULTS: The number of apoptotic cells detected was highest at day 15 (184+/-154) and then progressively decreased thereafter (day 30=159+/-197; day 45=80+/-167; day 60=0). The number of apoptotic enterocytes was found increased during mild (151+/-108) and moderate (281+/-161) allograft rejection, although a low apoptotic rate was observed in cases without rejection (59+/-13) and during severe (53+/-131) and chronic rejection (46+/-136). Furthermore the number of labeled cells was found inversely correlated with fibrosis (P<0.0001). There was no correlation between apoptosis and the presence or absence of DBMI; however, at day 15 rats receiving 1 mg/day of FK 506 had a significantly lower number of apoptotic cells detected (127+/-103 vs. 233+/-174; P<0.02). CONCLUSIONS: In this study the number of apoptotic cells correlated positively with mild and moderate rejection episodes. In case of severe and chronic rejection a low apoptotic rate was found due probably to extensive necrosis and fibrosis of the mucosa. These data suggest an important role of apoptosis in acute and chronic intestinal rejection in a rat model of intestinal transplantation. Determination of apoptosis in allografts might represent an early sign of small bowel rejection and a useful marker in defining the degree of rejection and its outcome/prognosis.

Animals↗
PubMed2001

Six-year clinical effect of donor bone marrow infusions in renal transplant patients.

BACKGROUND: To date, several single- and multicenter clinical trials have attempted to induce specific immunological unresponsiveness using donor bone marrow cell infusions to augment solid organ transplantation, but the outcomes have not been definitive. METHODS: Between September 1994 and May 1998, 63 cadaver (CAD) renal transplant recipients of either one or two postoperative donor bone marrow cell (DBMC) infusions were prospectively compared with 219 non-infused controls given equivalent immunosuppression. There was at least a 1 HLA DR antigen match present between donors and recipients. The immunosuppressive regimen included a 10-day course of OKT3 induction, and tacrolimus, mycophenolate mofetil, and methylprednisolone maintenance. A total 7.01x10(8)+/-1.9x10(8) (SD) DBMC/kg was infused into the CAD recipients on either days 4 and 11 (n=42) or one half of that dose on day 4 (n=21) postoperatively. Clinical follow-up has ranged from 2.9 to 6.3 years (mean, 4.7 years). Studies were also performed of humoral immunity and quantitative cellular chimerism. RESULTS: There is clear-cut equivalence in immunosuppressive dosaging and in the other major demographic variables in both groups. However, only 2/63 DBMC recipients had biopsy-proven chronic rejection, whereas 41/219 showed chronic rejection in the controls (P = <0.01). In both groups, mortality was not associated with rejection. The actuarial graft survival at 6.3 years in the CAD DBMC group was 84.3% compared with 72.2% in the control group (not statistically significant). However, if death with a functioning graft was excluded, graft survival was 94.1% in the DBMC group and 79.8% in the controls (P=0.039). Forty patients in the control group continue to have deteriorating renal function (increasing serum creatinine concentrations to 2 mg/dl and higher), compared with 2 patients in the DBMC group (P=0.04). In the DBMC group, chimerism in iliac crest marrow aspirates has increased 3-fold in yearly sequential measurements between 1 and 4 years postoperatively averaging 1.3+/-0.36% (SE) most recently. This has not occurred in the controls. CONCLUSIONS: There now appears to be more solid long-term evidence, in kidney transplant recipients prospectively receiving DBMC infusions, of an improvement in long-term graft survival, and of the degree of chimerism positively correlating with the absence of graft loss.

Adolescent↗
PubMed2001

Indications for pediatric intestinal transplantation: a position paper of the American Society of Transplantation.

Parenteral nutrition represents standard therapy for children with short bowel syndrome and other causes of intestinal failure. Most infants with short bowel syndrome eventually wean from parenteral nutrition, and most of those who do not wean tolerate parenteral nutrition for protracted periods. However, a subset of children with intestinal failure remaining dependent on parenteral nutrition will develop life-threatening complications arising from therapy. Intestinal transplantation (Tx) can now be recommended for this select group. Life-threatening complications warranting consideration of intestinal Tx include parenteral nutrition-associated liver disease, recurrent sepsis, and threatened loss of central venous access. Because a critical shortage of donor organs exists, waiting times for intestinal Tx are prolonged. Therefore, it is essential that children with life-threatening complications of intestinal failure and parenteral nutrition therapy be identified comparatively early, i.e. in time to receive suitable donor organs before they become critically ill. Children with liver dysfunction should be considered for isolated intestinal Tx before irreversible, advanced bridging fibrosis or cirrhosis supervenes, for which a combined liver and intestinal transplant is necessary. Irreversible liver disease is suggested by hyperbilirubinemia persisting beyond 3-4 months of age combined with features of portal hypertension such as splenomegaly, thrombocytopenia, or prominent superficial abdominal veins; esophageal varices, ascites, and impaired synthetic function are not always present. Death resulting from complications of liver failure is especially common during the wait for a combined liver and intestinal transplant, and survival following combined liver and intestinal Tx is probably lower than following an isolated intestinal transplant. The incidence of morbidity and mortality following intestinal Tx is greater than that following liver or kidney Tx, but long-term survival following intestinal Tx is now at least 50-60%. It is probable that outcomes shall improve in the future with continued refinements in operative technique and post-operative management, including immunosuppression.

Child↗
PubMed2001

Cytomegalovirus prophylaxis with ganciclovir and cytomegalovirus immune globulin in liver and intestinal transplantation.

Liver and intestinal transplant recipients at the University of Miami receive an intensive regimen of cytomegalovirus (CMV) prophylactic therapy consisting of a combination of CMV immune globulin intravenous (CMV-IGIV, CytoGam) and ganciclovir. The 5-year experience with this regimen in liver transplant patients showed effective CMV prophylaxis in this patient population. The importance of an effective prophylactic strategy was underscored by higher observed rates of chronic rejection and post-transplant lymphoproliferative disorder (PTLD) in CMV-infected patients. The use of CMV-positive donors for intestinal transplants did not increase the incidence of CMV disease. Intestinal transplant recipients had improved survival rates, reflecting an aggressive policy of monitoring, immunosuppression, and CytoGam plus ganciclovir prophylaxis.

Adult↗