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Biomedical subjects

F Filipponi

Publications and source records attributed to F Filipponi.

At least 37 records · Page 2Linked to original sources

Water-glove balloon system: a useful option to salvage liver grafts with postreperfusion suprahepatic vena caval kinking.

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.

Adult↗

Human preformed IgG combining with membrane-bound porcine serotransferrin lyse porcine endothelial cells through antibody-dependent cellular cytotoxicity.

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.

Amino Acid Sequence↗

[Orthotopic liver transplant. Analysis of costs related to anesthesiologic and intensive care phases].

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.

Anesthesia↗

Need and supply of liver grafts in Tuscany.

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.

Aged↗

Effect of cilastatin on cyclosporine-induced acute nephrotoxicity in kidney transplant recipients.

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.

Acute Disease↗

Surgical research in orthotopic liver transplantation: experiences in the pig model.

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.

Anesthesia↗

Segmental organization of the pig liver: anatomical basis of controlled partition for experimental grafting.

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.

Animals↗

Liver transplantation for end-stage liver disease associated with alpha-1-antitrypsin deficiency in children: pretransplant natural history, timing and results of transplantation.

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)

Child↗

Partial hepatic resection for ischemic graft damage after liver transplantation: a graft-saving option?

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.

Adult↗

Orthotopic liver transplantation in the pig: a surgical experience with 124 liver transplants.

From January 1988 to June 1990 one-hundred-twenty-four orthotopic liver transplantation (OLT) were performed in pigs, using a surgical procedure already described in the literature but with two major modifications. One of these modifications was the end-to-end microsurgical anastomosis of the proper hepatic arteries of the donor and recipient; the second one was the reduction in length of the donor suprahepatic vena cava to 1-2 mm before anastomosing it with the recipient suprahepatic vena cava at the level of the diaphragm. The first 24 transplants were used to develop the surgical technique. The latter was then applied to all subsequent 100 transplants, and results are herein presented. Good outcome of surgery appeared to depend on the modifications adopted in surgical technique, use of a pump-driven veno-venous bypass during the anhepatic phase of surgery, administration of cyclosporin A postoperatively, and training of the operator.

Anastomosis, Surgical↗

A new surgical model of acute liver failure in the pig: experimental procedure and analysis of liver injury.

In this research, the effects of portocaval shunt plus 70% partial hepatectomy were evaluated in 11 pigs. Hepatic coma and death from progressive liver failure occurred in 5 pigs between 14 and 64 h from surgery, whereas 3 pigs, which also showed symptoms of progressive liver failure, died of presumed gastric hemorrhage between 17 and 19 h after surgery. In 3 pigs, transient liver failure was followed by complete recovery, as judged by clinical, electroencephalographic and biochemical parameters. No case of death occurred among the pigs treated with portocaval shunt alone or 70% partial hepatectomy alone as controls. This new model for acute liver failure is reproducible, seems to be potentially reversible, causes death due to hepatic failure after a time period sufficiently long to allow for the institution of support procedures, is applied to a large animal and lacks relevant biohazard. Therefore, this model may be used to evaluate possible support procedures during acute liver failure.

Ammonia↗

Immunocytochemical and ultrastructural changes of islet cells in rats treated long-term with cyclosporine at immunotherapeutic doses.

Daily cyclosporine doses of 10 mg/kg body weight for 21 days in Wistar rats cause impairment in glucose homeostasis and changes in the amount of immunostainable hormones and in the ultrastructure of the cells of the pancreatic islets. CsA induces hyperglycemia and reduced glucose tolerance, and causes a decrease in immunoreactive insulin and an increase of somatostatin and pancreatic polypeptide (PP) immunoreactivities, leaving glucagon immunoreactivity unaffected. Ultrastructurally, different degrees of dilation of rough endoplasmic reticulum cisternae and enlargement of Golgi apparatus can be observed in B cells, together with a pronounced reduction in the number of secretory granules. Nevertheless, there were no apparent morphological changes of the other cytoplasmic organelles, suggesting that the drug, besides a depression of protein synthesis, as previously stated, also induces a substantial defect in granulogenesis, probably due to impairment in the intracellular transport of the hormone from the sites of synthesis to the secretory granules. The B cell alterations are not accompanied by any sign of B cell degeneration or death. Non-B cells did not show any of the ultrastructural changes found in B cells and were similar to those of the control rats. The above findings indicate that CsA at immunotherapeutic doses causes impairment in the secretory processes of B cells specifically. An hypothesis on the mode of action of CsA on B cells is drawn.

Animals↗

Morphological changes in rat pancreatic acinar cells induced by long-term treatment with cyclosporine and their reversal after withdrawal.

Cyclosporine (CsA), administered to rats at daily doses of 10 and 50 mg/kg body weight, for 21 days, influenced negatively the structures involved in the synthesis, storage and secretion of digestive enzymes in pancreatic acinar cells. A dose-related, significant reduction in basophilic cell regions, secretion granule content, and overall size of acinar cells was appreciable by light microscopy and morphometry. By electron microscopy, the acinar cells of the rats given 10 mg/kg/day CsA were similar to the controls, whereas with the higher dose most cells showed reduction in the size of nucleoli, increase in the number of lysosomes, and evidence of autophagy. In only a few cells was autophagy particularly severe and involved almost the entire cytoplasm. Nine weeks after withdrawal from CsA treatment, the structural recovery of acinal cells was complete, and features indicating enhanced protein synthesis and mitochondrial multiplication were observed by electron microscopy. In conclusion, prolonged administration of CsA to rats induces changes in the acinar cells indicating a depression of their activity, without substantial impairment in the viability of the most of them, even at high doses. This accounts for complete restoration of the acinar tissue upon withdrawal.

Animals↗

Bioavailability of intramuscular ciclosporin in the pig.

We conducted a cross-over single-dose pharmacokinetic study in 4 pigs to measure the bioavailability of ciclosporin (CS) after intravenous and intramuscular administration. Each animal was given 5 mg/kg i.v. followed by 20 mg/kg i.m. after 1 week. Serial blood samples were taken over 36 h after each dose, and the concentration of CS was assayed by radioimmunologic methods. The pharmacokinetic parameters after intravenous administration were (mean +/- SD; n = 4): clearance = 327 +/- 21 ml/h/kg; volume of distribution = 7.2 +/- 2.8 liters/kg. The same parameters after intramuscular dosing were: clearance = 326 +/- 59 ml/h/kg; volume of distribution = 6.9 +/- 2.1 liters/kg. The percent bioavailability of intramuscular CS was 101.9 +/- 13.3 with a mean absorption time of 10.6 +/- 2.7 h. Our results indicate that following a single dose, the percent bioavailability of intramuscular CS in pigs is considerably greater than that reported in previous studies.

Animals↗

Alterations in the fine structure of the pig liver upon cold ischemia.

The fine structure of the pig liver was examined after 30 min of warm ischemia at 37 degrees C, after 2 h of cold ischemia at 4 degrees C and after 30 min of warm ischemia followed by a further 30 min of cold ischemia. After warm ischemia, limited mitochondrial swelling was observed in hepatocytes. After cold ischemia, alone or following warm ischemia, vesiculation and vacuolation of the hepatocyte cytoplasm and appearance of intrasinusoidal blebs deriving from hepatocytes were observed with different intensity among the animals. These findings suggest that cooling and storing the liver at 4 degrees C may lead to injury, which could negatively influence the viability of the organ, with different intensity from case to case.

Animals↗