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Biomedical subjects

A D Pinna

Publications and source records attributed to A D Pinna.

At least 55 records · Page 3Linked to original sources

Early experiences with a porcine hepatocyte-based bioartificial liver in acute hepatic failure patients.

Orthotopic liver transplantation (OLT) is the only effective therapeutic modality in severe acute hepatic failure (AHF). The scarcity of organs for transplantation leads to an urgent necessity for temporary liver support treatments in AHF patients. A hepatocyte-based bioartificial liver (BAL) is under investigation with the main purpose to serve as bridging treatment until a liver becomes available for OLT, or to promote spontaneous liver regeneration. We developed a novel radial-flow bioreactor (RFB) for three-dimensional, high-density hepatocyte culture and an integrated pumping apparatus in which, after plasmapheresis, the patient's plasma is recirculated through the hepatocyte-filled RFB. Two hundred thirty grams of freshly isolated porcine hepatocytes were loaded into the RFB for clinical liver support treatment. The BAL system was used 8 times in supporting 7 AHF patients in grade III-IV coma, all waiting for an urgent OLT Three patients with no history of previous liver diseases were affected by fulminant hepatic failure (FHF) due to hepatitis B virus, 3 by primary non-function (PNF) of the transplanted liver, and one by AHF due to previous abdominal trauma and liver surgery. Six out of 7 patients underwent OLT following BAL treatment(s), which lasted 6-24 hours. All patients tolerated the procedures well, as shown by an improvement in the level of encephalopathy, a decrease in serum ammonia, transaminases and an amelioration of the prothrombin time, with full neurological recovery after OLT Our initial clinical experience confirms the safety of this BAL configuration and suggests its clinical efficacy as a temporary liver support system in AHF patients.

Adolescent↗

Intestinal transplantation for the treatment of desmoid tumors associated with familial adenomatous polyposis.

BACKGROUND: Desmoid tumors associated with familial adenomatous polyposis (FAP) are locally invasive. Often occurring in the mesentery of the intestine, they sometimes recur after resection. Complications can include intestinal failure and dependence on parenteral nutrition. We describe 9 patients who underwent intestinal transplantation for the treatment of desmoid tumors associated with FAP. METHODS: Records of patients undergoing intestinal transplantation for desmoid tumors at 2 transplant centers were reviewed for patient age, sex, type of graft, procedure date, tumor site, desmoid complications, medications, extracolonic manifestations, status at follow-up, and length of survival. RESULTS: Nine patients with FAP and intestinal failure caused by desmoid tumors were treated with isolated intestinal (n = 6), multivisceral (n = 2), or combined liver-intestinal transplantation (n = 1). Desmoid tumors recurred in the abdominal walls of 2 patients. Two patients died: one as a result of sepsis, the other because of a rupture of a mycotic aneurysm of the aortic anastomosis. One graft lost to severe rejection was replaced with a second intestinal graft. Eleven to 53 months after transplantation, 7 patients were alive, well, independent of parenteral treatment, and leading apparently normal lifestyles. CONCLUSIONS: Transplantation of the intestine alone or as part of a multivisceral transplantation may help rescue otherwise untreatable patients with complicated desmoid tumors.

Adenomatous Polyposis Coli↗

Sirolimus in pediatric gastrointestinal transplantation: the use of sirolimus for pediatric transplant patients with tacrolimus-related cardiomyopathy.

Hypertrophic obstructive cardiomyopathy (HOCM) associated with the use of tacrolimus is a rare complication of liver and intestinal transplantation seen almost exclusively among pediatric patients. Reduction of tacrolimus dosage or conversion to cyclosporin A (CsA) has been used as an effective treatment in reviewed cases. We present three pediatric transplant recipients who developed hypertrophic obstructive cardiomyopathy while under tacrolimus immunosuppression and were treated with conversion to sirolimus (Rapamycin). The patients (ages 6 yr, 12 yr and 11 months) were transplant recipients (liver, n = 2; liver and intestine, n = 1) who developed significant cardiomyopathy 15 and 96 months post-transplant. One patient died of post-transplant lymphoproliferative disorder 21 days after starting sirolimus. One patient had received two liver transplants and had been on CsA for 12 yr before conversion to tacrolimus at 60 months post-transplant for acute and chronic rejection. The surviving patients were receiving mycophenolate mofetil, tacrolimus and steroids at the time of diagnosis. Dose reduction of tacrolimus and treatment with beta blockers failed to alleviate the hemodynamic changes. The patients were converted to sirolimus 1.6, 37 and 148 months post-transplant and maintained a whole-blood trough level of 15-20 ng/mL 21 days after starting sirolimus. Repeat echocardiograms in the surviving patients showed improvement in cardiomyopathy. One patient had one rejection episode (intestinal biopsy, mild acute cellular rejection) after starting sirolimus that responded to a transient increase in steroids. The early demise of the third patient after sirolimus conversion prevented an adequate assessment of cardiomyopathy. Conversion to sirolimus was associated with a reduction in the cardiomyopathy of the two surviving patients while still providing effective immunosuppression. To our knowledge this observation has not been previously reported.

Acute Disease↗

Graft failure secondary to necrotizing enterocolitis in multi-visceral transplantation recipients: two case reports.

We report on two recipients of multi-visceral grafts who exhibited sudden onset of acute abdomen discomfort 2 weeks post-transplantation after a fairly uneventful immediate post-operative course. Both patients were shown to have pneumatosis intestinalis and one had air in the portal vein. Both patients underwent exploration, which showed non-viable intestine (terminal ileum and colon in the first patient and the entire small intestine distal to the ligament of Treitz in the second patient). There was no vascular thrombosis. The necrotic intestine was resected in both cases. The first patient developed sepsis and died 15 days later despite the rescue efforts. The second patient was re-transplanted twice and is doing well. The histopathology of the segments involved revealed cryptitis, vasculitis, and features of transmural necrosis. Accordingly, both clinical and pathologic features are diagnostic of necrotizing enterocolitis. To our knowledge this is the first report of this complication following intestinal or multi-visceral transplantation.

Adolescent↗

Multivisceral transplantation for megacystis microcolon intestinal hypoperistalsis syndrome.

BACKGROUND: Megacystis microcolon intestinal hypoperistalsis syndrome (MMIHS) is a rare autosomal recessive disorder causing a functional neonatal bowel obstruction. Its etiopathogenesis is not fully understood. The prognosis is poor in the majority of cases; most patients die before the age of 6 months. In this report, we describe our experience with three patients with MMIHS in whom multivisceral transplantation was performed. METHODS: Three patients with MMIHS underwent multivisceral transplantation. All patients were females with a history of long-term total parenteral nutrition (TPN) with TPN-related cholestatic liver disease. RESULTS: Patient 1 died 17 months after transplantation because of aspiration after revision of her feeding gastrostomy. At the time of death, the graft was functioning and the patient was completely off TPN. Patient 2 is alive 17 months after transplant. She is a fully functional, active 2-year-old and has also recently begun oral feeding after intensive rehabilitation. Patient 3 died on day 44 of multisystem failure. CONCLUSIONS: This is the first report in the literature of multivisceral transplantation for MMIHS. Although one of the three patients died 44 days after surgery from multiorgan system failure, the other two patients had long-term survival after transplant and both grew well on enteral feeding alone. One patient died 17 months from a non-transplant-related complication, while the other is living at home off of TPN, with almost complete dietary rehabilitation 17 months after transplant. Our case reports suggest that multivisceral transplantation is a valuable therapeutic option for patients affected by MMIHS with TPN-induced liver failure.

Abnormalities, Multiple↗

Thrombocytopenia after liver transplantation.

BACKGROUND: Thrombocytopenia after orthotopic liver transplantation (OLT) is a well recognized and prevalent early postoperative complication. The etiology, as well as the effect of this phenomenon on transplant outcome, however, are vague. The aims of this study are to identify factors contributing to thrombocytopenia and to ascertain whether there is any correlation with early rejection and ultimate survival. METHODS: This study examines 541 OLTs (541 grafts in 494 patients) that were transplanted at the University of Miami during the 3-year period from June 1994 to September 1997. The patients with severe postoperative thrombocytopenia (nadir platelet count [PLT] < 20,000/mm3), as well as the whole group of patients, were analyzed. The preoperative PLT, intra-operative platelet transfusion requirements, cross-match, recipient and donor cytomegalovirus (CMV) status, infusion of donor bone marrow cells (DBMC), occurrence of early rejection episodes (in the first posttransplant month), and re-transplantation were factors examined for any association with thrombocytopenia. Total bilirubin (TB) and direct bilirubin (dB), hematocrit, white blood cell count (WBC), aspartate aminotransferase and alanine aminotransferase, determined on the day that platelets reached a nadir (nadir day), were also analyzed. RESULTS: In 90.9% of the cases, there was a 56.5%+/-23.5% fall in platelets in the immediate posttransplant period (first 2 weeks), but the mean PLT exceeded preoperative levels during the 3rd and 4th postoperative weeks. The nadir of the drop in the PLT most commonly occurred on posttransplant day 4. For preoperative PLT, platelet transfusions during the operation, re-transplantation, early rejection, cross-match, and recipient CMV status, there was significant statistical correlation with any degree of postoperative thrombocytopenia. Four of these factors, preoperative PLT, intra-operative platelet transfusions, re-transplantation, and early rejection, were found to be independently associated with thrombocytopenia in general. None of them was found to be independently correlated with severe thrombocytopenia. A statistically significant correlation between bilirubin and WBC on the nadir day and the degree of thrombocytopenia was observed. No correlation was found between infusion of DBMC or donor CMV serology and thrombocytopenia. Both the nadir PLT and the percentage of the platelet fall were independent predictive factors (p<0.01 and 0.005, respectively) of patient and graft survival. CONCLUSIONS: Thrombocytopenia in the immediate posttransplant period is correlated with low preoperative PLT, massive platelet transfusions, and re-transplantation. These factors reflect a poor preoperative condition. There is also a correlation with allograft dysfunction, rejection, and poorer patient and graft survival. A rise in the mean PLT after the 2nd postoperative week reflects proper graft function.

Adolescent↗

Inclusion of entire pancreas in the composite liver and intestinal graft in pediatric intestinal transplantation.

An entire pancreatico-duodenal complex was included in the liver and intestinal graft in eight children who received small-size grafts. This method showed several advantages compared to the traditional approach. They included reducing time for graft preparation by eliminating donor pancreas resection, no necessity of biliary reconstruction and leaving natural tissue support for blood vessels. The method was not associated with an increased risk of complications such as pancreatitis or rejection. It should be considered in pediatric liver and intestinal transplant recipients who require small-size grafts.

Age Factors↗

Unusual presentation of graft-versus-host disease in pediatric liver transplant recipients: evidence of late and recurrent disease.

Graft-versus-host disease (GvHD) is a multi-organ disease caused by mature donor T cells that are activated by alloantigens expressed by the host antigen-presenting cells. GvHD has been reported after solid organ transplantation with two principal presentations: humoral and cellular. In the cellular type of GvHD after liver transplantation the symptoms are identical to the GvHD after bone marrow transplant, except that the liver is spared because it lacks host antigens. We have described three cases of intestinal GvHD after pediatric liver transplant with an unusual recurrent late presentation in two patients. Two patients were female, and their age at the time of transplant was 8 and 9 months, respectively, and one was an 8-month-old male. They all received reduced liver allografts of identical blood type from three different donors. One patient received two doses of donor bone marrow cell infusion. Two patients received double immunosuppressive therapy constituted by tacrolimus at a dose of 0.05 mg/kg p.o. b.i.d. and steroids 10 mg p.o. daily. One patient received a triple drug immunosuppression with tacrolimus (0.05 mg/kg p.o. b.i.d.), steroids (10 mg p.o. daily) and mycophenolate mofetil (125 mg p.o. b.i.d.). Diagnosis of intestinal GvHD was confirmed histologically on intestinal biopsies performed at the time of presentation of the clinical symptoms or at autopsy.

Adolescent↗

Comparison of tacrolimus with microemulsion cyclosporine as primary immunosuppression in hepatitis C patients after liver transplantation.

BACKGROUND: Immunosuppression in patients with hepatitis C virus (HCV) following orthotopic liver transplantation can lead to significant increases in serum viral loads. Our aim was to analyze the effect of a randomized study of two immunosuppressive agents (tacrolimus vs. microemulsion cyclosporine) on the outcome of HCV patients following orthotopic liver transplantation. METHODS: From December 1995 to September 1996, 50 adult patients transplanted for HCV cirrhosis were randomly assigned to receive tacrolimus (Prograf) (group 1, 25 patients) or microemulsion cyclosporine (Neoral) (group 2, 24 patients). All patients received alpha-interferon after transplantation, and the overall steroid doses were no different between the groups. Serum RNA levels were measured by signal amplification of Chiron. Biopsies were taken when transaminases were greater than 2x base line or when there was an inappropriate response to alterations in immunosuppression regimens. RESULTS: There were more episodes of rejection in the Neoral group, but there were no differences in bacterial and viral infections, nor in the rate of HCV recurrence between the two groups. There were seven deaths in group 1 and eight in group 2. Overall patient and graft survival rates in the Prograf and Neoral groups at 18 months were 72 and 68% and 67 and 64%, respectively. CONCLUSIONS: (a) Both immunosuppression regimens had similar HCV recurrence rates; (b) there were no differences in bacterial or opportunistic infections; and (c) patient and graft survival was similar between the two groups.

Adult↗

Liver transplantation with cavoportal hemitransposition in the presence of diffuse portal vein thrombosis.

BACKGROUND: Orthotopic liver transplantation is possible even in the presence of recipient portal vein thrombosis, provided that hepatopetal portal flow to the graft can be restored. On rare occasions this is not possible due to diffuse thrombosis of the portal venous system. In these cases, successful liver transplantation has been considered impossible. Portocaval transposition was introduced in the pretransplantation era to study the effect of systemic venous flow on the liver and has been used in three patients for the treatment of glycogen storage disease. We used portocaval hemitransposition (portal perfusion with inflow from the inferior vena cava) in liver transplantation when portal inflow to the graft was not feasible. We are reporting the collective experience of nine patients from four liver transplant centers. METHODS: Cavoportal hemitransposition was used in nine patients. In seven of these cases, the technique was used during the original transplant (primary group). In two cases, it was used after the portal inflow to the first transplant had clotted (secondary group). RESULTS: Five of seven patients in the primary group are alive after intervals of 6-11 months. The two patients in the rescue group died. In the successful cases, liver function and histology were indistinguishable from those of conventional liver transplantation. Ascites disappeared within 3-4 months and the patients were able to return to their normal activities. Postoperative variceal bleeding necessitated splenectomy and gastric devascularization in one case and splenic artery embolization in another case. Bleeding was controlled in both these cases. Splenectomy and gastric devascularization were performed prophylactically in one patient with a history of variceal bleeding in order to prevent this complication after transplantation. CONCLUSION: Portocaval hemitransposition maybe useful in liver transplantation when hepatopetal flow to the liver graft cannot be established by other techniques. Rescue after failure of conventional technique was not possible in two patients.

Adult↗