Usefulness of direct sequencing in the detection of microchimerism in liver transplant recipients.
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Biomedical subjects
Publications and source records attributed to F Filipponi.
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BACKGROUND: A large animal model of total hepatectomy is suitable to test the efficacy of any system designed to support patients in hepatic coma. The models previously described in the pig entail a significant degree of surgical trauma, which might alter the evolution of the ensuring hepatic failure and compromise the reproducibility of the model. METHODS: Twenty-eight pigs underwent a total hepatectomy according to a new technique. A model was considered satisfactory when it required no blood transfusions and when hematologic and hemodynamic parameters determined before, during, and until 4 hours after hepatectomy showed no significant variations. Moreover, to revive the pattern of hepatic coma produced in the anhepatic model, 7 pigs were monitored until brain death occurred. RESULTS: Twenty-five pigs (89%) underwent a smooth total hepatectomy with minimal variations of the selected parameters. They constituted a highly homogeneous group. Survival of the 7 pigs, followed up until brain death occurred, ranged from 625 to 1595 minutes (mean 1013.57 minutes). The animals remained stable until a few hours before brain death, an event heralded by a final sharp increase of the serum ammonia level and by a well-evident decline of both arterial pressure and liver-dependent clotting factors. CONCLUSIONS: This technique of total hepatectomy allows the construction of a reproducible model of anhepaty suitable to test the efficacy of any system conceived to temporarily replace hepatic functions.
BACKGROUND: To evaluate an early tracheal extubation feasibility in previously unselected orthotopic liver transplantation (OLT) patients. METHODS DESIGN: retrospective analysis. SETTING: National Health System Intensive Care Unit. PATIENTS: all the patients who underwent OLT during 1997 at our institution were evaluated. The anesthestic management was the same for all of them and a veno-venous bypass was always used during the anhepatic phase. Tracheal extubation was performed when metabolic and haemodynamic parameters were stable; the following extubation criteria were also considered: no residual curarization, normocarbia, ability to keep the airway patent, good respiratory drive, ability to carry out simple orders. No pre- or intraoperative criteria, as previously reported in the literature for OLT patients, were followed to perform tracheal extubation in the postoperative period. RESULTS: During 1997 forty OLTs were performed in 38 patients. Twenty-eight patients were successfully extubated within 3 hours from the end of the surgical procedure; three patients were extubated within 6 hours and three within 24 hours from the end of surgery; four patients needed more then 24 hours of ventilation or were impossible to wean. No patient was re-intubated. A correlation appeared evident between early extubation and the amount of the transfused red cell units, kidneys and lungs function, cardiovascular efficiency; no correlation emerged with patients age or the pre-transplant severity of the hepatic disease. CONCLUSIONS: To perform a safe early tracheal extubation in previously unselected OLT patients is feasible and it can be carried out in a wide number of them. The previously reported timing characterizing as "early" a tracheal extubation should be moved from 8 to 3 hours.
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BACKGROUND: Although exceedingly rare, kinking of suprahepatic vena cava after liver transplantation can lead to both graft failure and patient demise. The features of a case of suprahepatic vena caval kinking are herein reported along with the description of an original solution adopted to rescue the graft. METHODS: In order to correct vascular kinking, two surgical gloves filled with sterile saline solution were placed in appropriate positions in the subdiaphragmatic space. RESULTS: Caval obstruction was immediately relieved. Over a period of 7 days, gloves were progressively deflated and eventually removed without need for laparotomy. Vena caval kinking did not recur. CONCLUSIONS: The "water-glove balloon system" described in this report seems to be an efficient and inexpensive method to rescue liver grafts in the presence of kinking or torsion of the suprahepatic vena cava. Surgeons dedicated to the transplantation of the liver should therefore retain this option in their cultural background.
Preformed antibodies are involved in xenograft rejection. The purpose of this work was to characterize porcine xenoantigens recognized by human preformed IgG (hpIgG), and to investigate the role of hpIgG in xenogeneic rejection. IgG eluted from porcine livers perfused with human plasma, human sera and total human IgG were immunoblotted on porcine aortic endothelial cell extracts. The amino acid sequence of a 76-kDa antigen constantly revealed was 100% homologous with porcine serotransferrin (psTf). hpIgG from human sera, human IgG1 and IgG2 and F(ab')2gamma specifically bound to psTf. Neutralization by psTf abolished that binding. Although alpha1,3-linked galactose residues (Gal(alpha)1,3Gal) is the dominant epitope recognized by preformed antibodies in the swine-to-human combination, the analysis of carbohydrate composition of psTf showed that the molecule was devoid of Gal(alpha)1,3Gal moieties and that preformed anti-psTf IgG bound to epitopes localized on the peptide core of the molecule. Purified human anti-psTf IgG antibodies were able to bind to psTf linked to its receptor on porcine endothelial cells, and to kill those cells through antibody-dependent cellular cytotoxicity.
BACKGROUND: To evaluate anesthesia and Intensive Care Unit (ICU) costs for Orthotopic Liver Transplantation (OLT) through a point by point analysis of the entire process from anesthesia induction to ICU discharge. DESIGN: Retrospective analysis. SETTING: Regional Transplantation Centre participating to the Italian National Health Care System. METHODS: Anesthesia and ICU costs for each OLT performed during 1997 were estimated through the analysis of costs of the following categories: drugs, medical and nurse staff, blood bank, radiology, laboratory, haemoderivates. RESULTS: Forty OLTs were performed in 38 recipients during the study period. The total charges for the anesthesia and ICU management of these patients calculated in US dollars were 583.433,23 (considering the exchange rates valid in January 1998). ICU costs resulted approximately 2.5 times higher than those for anesthesia. Blood bank and drugs were the categories that had the greatest impact on the final expense whereas laboratory had the lowest. The charges referred to medical and nurse staff resulted higher in the ICU than for anesthesia. CONCLUSIONS: The Italian National Health Care System has to deal with limited resources; costs analysis of high-tech procedures as OLT is of basic importance to optimise resources allocation and to enforce money-saving actions.
BACKGROUND: Epidemiological data are fundamental to adequately plan the activity of a liver transplantation centre. AIM: To evaluate the ratio between need and supply of liver grafts in Tuscany and to develop a regional strategy aimed at increasing donor recruitment. METHODS: The need for liver grafts was estimated on the basis of an epidemiological study: 19 Medical Units were requested to fill in a questionnaire inquiring into all Tuscan patients evaluated for liver disease during three different periods of one month each in 1996. The information collected was matched with the selection criteria currently employed at our centre and the patients were classified into the following four categories: 1. current transplantation candidates; 2. future transplantation candidates; 3. candidates not suitable on account of age; 4. candidates not suitable on account of exclusion criteria. The number of liver donors was obtained from the donor registry. RESULTS: Questionnaires were returned for a total of 452 patients: 27 (5.97%) were classified as current transplantation candidates, 62 (13.72%) as future transplantation candidates and 19 (4.20%) as candidates not suitable on account of age. The annual incidence and prevalence of transplantation candidates were 14.7 and 30.6 cases per million inhabitants, respectively. If age (> or = 61 years) was not considered in the exclusion criteria, the annual prevalence of transplantation candidates reached 52.1 cases per million inhabitants. During the same period there were 44 organ donors (12.2 donors per million inhabitants) of whom 33 were suitable for liver donation (9.3 liver donors per million inhabitants). To reduce this discrepancy a new programme for organ recruitment, based upon the Spanish model, has been recently employed. CONCLUSIONS: The annual need for liver grafts in Tuscany largely exceeds the number of donors currently available. It is hoped that the new regional programme for organ recruitment will improve these figures.
BACKGROUND: Cyclosporine (CsA)-induced acute nephrotoxicity could be reduced by prevention of parenchymal accumulation of the drug itself. The objective of this prospective study was to evaluate whether cilastatin, an inhibitor of active tubular resorption of CsA, reduces CsA-induced acute nephrotoxicity in kidney graft recipients. METHODS: Sixty-nine kidney recipients with immediate graft functional recovery were randomly assigned to either the treatment group (imipenem/cilastatin, n=33) or the control group (ceftazidime, n=36). All patients followed a standard immunosuppressive regimen based on CsA and low-dose prednisone. Graft function and CsA levels were evaluated 3, 5, 10, 15, and 30 days after transplantation. RESULTS: Compared with the control group, imipenem/cilastatin administration reduced the serum creatinine level in the first 2 weeks after transplantation, reaching a significant effect on postoperative day 10 (P<0.05). No significant differences were demonstrated between the two groups for CsA levels, patient and graft survival, and all the other examined parameters. CONCLUSIONS: Our findings support the hypothesis that cilastatin administration can reduce CsA-induced acute nephrotoxicity after kidney transplantation.
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Since the very beginning of liver transplantation in humans, research in animals has had close relationship with clinical practice. Results obtained in animals have been transferred to the clinics and problems borne in the clinics have been addressed again in animals for to be answered clearly. In this review the authors report their experience of transplantation in the pig model and discuss the significance of a team cooperation in the laboratory as a preparatory step for clinical practice.
Segmental anatomy has been investigated on 54 pig livers by bench-top radiology and ultrasonography of hepatic and portal vessels and bile ducts and dissection of suprahepatic veins. Eight segments were recognized, homologous to those of the human liver. Major variations were found only of arterial distribution. The inferior vena cava invariably ran within the parenchyma of the right lobe and close to the liver hilum; suprahepatic veins were also entirely intraparenchymal. Therefore, the pig liver can easily be divided into two halves, but only the right one can be used for reduced-size grafting into a recipient.
Alpha-1-antitrypsin deficiency is an inborn metabolism error which can cause emphysema and liver disease. As regards the pathophysiology of liver disease, this deficiency is poorly understood, and it is also not known why only a small proportion of Pi ZZ individuals progress towards cirrhosis and liver failure. Since there is no specific therapy for end-stage liver disease associated with alpha-1-antitrypsin deficiency, patients are considered candidates for liver transplantation. In this paper, the natural history of 16 children who underwent liver transplantation is reviewed. Fourteen patients had neonatal cholestasis as a first symptom of the disease and hepatosplenomegaly was present in all children by the age of 12 months. In 11 children, jaundice recurred, always with liver function deterioration. Two patients had a histological paucity of interlobular bile ducts and required early transplantation due to rapid progression of liver failure. At the time of pretransplant assessment, all the patients in this study had portal hypertension and seven of them had experienced at least one episode of gastrointestinal bleeding. One child had moderate intrapulmonary shunts with hypoxemia, but the others had normal spirometry and blood gases. There was no other extrahepatic complication of alpha-1-antitrypsin deficiency. Eighteen orthotopic liver transplantations were performed in 16 patients. One patient died 8 days after retransplantation due to graft necrosis. Fifteen patients (94%) were alive after a median follow-up of 22 months with an excellent quality of life, normal serum alpha-1-antitrypsin levels and without evidence of liver disease recurrence or pulmonary complications.(ABSTRACT TRUNCATED AT 250 WORDS)
BACKGROUND: Intrahepatic biliary strictures or parenchymal infarcts may occur after liver transplantation as a complication of ischemic damage to the graft. In some selected cases the lesions appear to be confined to a part of the liver. We report our experience with partial graft resection in this setting. METHODS: From January 1984 to December 1991, 286 liver transplantations were performed in 257 recipients. Seven patients, three children and four adults, underwent partial hepatectomy 3 to 218 weeks after liver transplantation of a full-size graft. The clinical presentation included septic parenchymal infarcts (n = 4) and nonanastomotic biliary strictures (n = 3) complicating (n = 5) artery thrombosis or not (n = 2). There were four left hepatectomies, two left lobectomies, and one right hepatectomy. In four instances partial hepatectomy was performed after failed attempt at biliary reconstruction (n = 2) or arterial revascularization (n = 2). Partial graft resection was performed extrafascially without Pringle's maneuver and mobilization of the remnant liver to preserve its vascularization. RESULTS: No surgical complications occurred, and none of the patients experienced acute hepatic failure during the postoperative period. All patients were discharged home 10 to 96 days (median, 23 days) after liver resection. Two patients had recurrent ischemic cholangitis. One patient underwent successful regrafting for recurrent Budd-Chiari syndrome; one patient died of tumor recurrence. Six patients were alive with a follow-up ranging from 12 to 45 months. CONCLUSIONS: These results suggest that partial graft resection is a safe and graft-saving option after liver transplantation in selected patients with localized ischemic damage of the graft.