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Biomedical subjects

E Benedetti

Publications and source records attributed to E Benedetti.

At least 37 records · Page 2Linked to original sources
PubMed2004

Severe hemolytic anemia due to passenger lymphocytes after living-related bowel transplant.

BACKGROUND: Hemolytic anemia following solid organ transplant may be caused by 'passenger' lymphocytes producing antibodies against erythrocytes. This phenomenon has never been described after intestinal transplant. MATERIALS AND METHODS: We report a case of severe, immune-mediated hemolysis due to symptomatic passenger lymphocyte syndrome (PLS) in a 4-yr-old recipient of living donor small bowel transplant. The Coombs'-positive hemolysis was caused by anti-A,B antibodies derived from donor lymphocytes in an ABO-compatible donor-recipient pair (O into A). RESULTS: This complication was successfully and efficiently treated by the novel combined use of group O RBC transfusion, plasmapheresis and rituximab (anti-CD20). CONCLUSIONS: A severe hemolytic anemia due to PLS can occur in bowel transplantation. This complication should be considered when performing ABO-incompatible bowel transplant with a blood group O donor and an A or B recipient. Treatment with plasmapheresis, blood group O transfusion and rituximab has proved successful in our case.

ABO Blood-Group System↗
PubMed2003

Living-related bowel transplantation to treat short bowel syndrome in a four-year-old child: a case report.

PURPOSE: Short bowel syndrome (SBS) is an extremely challenging clinical problem in children. Although many patients can be maintained for a period of time on total parenteral nutrition (TPN), many of these children suffer from the morbidity and mortality associated with sequential central line infections, venous thromboses, and TPN-induced liver failure. Intestinal transplantation often is the only chance for long-term survival. Unfortunately, many children die every year waiting for size-matched cadaveric intestine to become available. METHODS: After our success with living-related bowel transplantation in adults, the authors successfully transplanted 150 cm of maternal ileum into a 4-year-old 10-kg child with profound malnutrition from SBS and advanced TPN-induced liver failure. Because of the size mismatch, the abdominal cavity could not be closed primarily. The defect was covered with absorbable mesh and subsequently with skin graft. RESULTS: The patient is home with excellent bowel and liver function, off hyperalimentation, and on a regular diet. No rejection has been encountered. CONCLUSIONS: Living-related intestinal transplantation is a life-saving alternative to cadaveric intestinal transplantation in children with short bowel syndrome.

Child, Preschool↗
PubMed2002

The role of molecular monitoring in autotransplantation for non-Hodgkin's lymphoma.

Seventy-two patients with non-Hodgkin's lymphoma were evaluated for the presence of molecular markers (IgH, bcl-1, bcl-2 rearrangement) on bone marrow, at diagnosis and after PBSCT, and on harvests in order to find a possible predictive role of minimal residual disease on treatment outcome. At diagnosis, 41 (59%) out of 69 available bone marrows showed molecular involvement. Fifty-six percent of leukaphereses were involved, mainly indolent lymphoma (P = 0.001) or advanced disease (P = 0.01). Ex vivo purging cleared only one stem collection out of 31 PCR-positive leukaphereses. Aggressive lymphomas showed both a longer overall survival (OS) (P = 0.03) and relapse-free survival RFS (P = 0.02) when transplanted with unpurged stem cells, whereas indolent NHL survival was not influenced by ex vivo purging. Twenty out of 26 samples taken during follow-up had bone marrow involvement at diagnosis. Of these, 15 cleared their bone marrow; both OS and RFS were significantly longer in the PCR-negative cases (P = 0.05 and P = 0.005). At 1 year after PBSCT, 75% of patients were PCR negative, with 50% molecular remissions; the relapse rate was 55% for patients still PCR positive vs 29% for those who were PCR negative. Thus, after high-dose chemotherapy, close molecular monitoring of MRD using qualitative PCR techniques seems to represent a reliable prognostic indicator.

Adolescent↗
PubMed2001

Crystal structure of the wild-type and D30A mutant thioredoxin h of Chlamydomonas reinhardtii and implications for the catalytic mechanism.

Thioredoxins are ubiquitous proteins which catalyse the reduction of disulphide bridges on target proteins. The catalytic mechanism proceeds via a mixed disulphide intermediate whose breakdown should be enhanced by the involvement of a conserved buried residue, Asp-30, as a base catalyst towards residue Cys-39. We report here the crystal structure of wild-type and D30A mutant thioredoxin h from Chlamydomonas reinhardtii, which constitutes the first crystal structure of a cytosolic thioredoxin isolated from a eukaryotic plant organism. The role of residue Asp-30 in catalysis has been revisited since the distance between the carboxylate OD1 of Asp-30 and the sulphur SG of Cys-39 is too great to support the hypothesis of direct proton transfer. A careful analysis of all available crystal structures reveals that the relative positioning of residues Asp-30 and Cys-39 as well as hydrophobic contacts in the vicinity of residue Asp-30 do not allow a conformational change sufficient to bring the two residues close enough for a direct proton transfer. This suggests that protonation/deprotonation of Cys-39 should be mediated by a water molecule. Molecular-dynamics simulations, carried out either in vacuo or in water, as well as proton-inventory experiments, support this hypothesis. The results are discussed with respect to biochemical and structural data.

Amino Acid Sequence↗
PubMed2001

Pyruvate inhibits hepatic ischemia-reperfusion injury in rats.

BACKGROUND: Ischemia/reperfusion (I/R) injury is a limiting factor in liver transplantation. We have recently shown that pyruvate (PY) inhibits intestinal and renal I/R injury. This study aims to evaluate the protective effect of PY on hepatic I/R injury. METHODS: ACI rats were treated with PY, whereas control animals received placebo. Rats were killed after 60 min of partial hepatic ischemia and after 2, 6, 24, and 48 hr of reperfusion. For each time point, serum aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase were measured, and liver biopsy specimens were obtained to evaluate morphology, DNA fragmentation, and apoptosis (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling). RESULTS: The survival rate 48 hr after I/R was 83% in the control group, and 100% in the PY-treated group (P>0.05). Increased enzymatic levels and histologic findings showed increased liver damage in the untreated group compared with PY. In control rats, apoptosis was enhanced after 1 hr of ischemia and peaked after 2 hr of reperfusion, to decrease gradually 48 hr after reperfusion; in the PY group apoptosis was delayed and reduced. After 1 hr of ischemia, the number of apoptotic nuclei was significantly increased in control livers compared with normal preischemic livers, whereas the number was significantly reduced by PY. After 2 hr of reperfusion, the maximum number of apoptotic cells was observed, whereas PY significantly reduced the amount of apoptotic cells (P<0.05). Apoptosis was delayed in PY-treated livers to 6 hr after reperfusion, peaking at a significantly lower count compared with placebo-treated controls (P<0.05). CONCLUSION: These data indicate that PY has a protective effect on I/R injury of the liver.

Animals↗
PubMed2001

Risk factors for failure to meet listing requirements in liver transplant candidates with alcoholic cirrhosis.

BACKGROUND: The majority of liver transplant centers require a 6-month abstinence period before listing candidates for liver transplantation with alcoholic cirrhosis and a persistent sobriety thereafter. We attempted to identify risk factors for failure to comply with these requirements. METHODS: Ninety-nine consecutive patients with alcoholic cirrhosis were referred for liver transplant evaluation between September 1996 and May 1998. The mean age was 49 years, 74% were male, and 54% were hepatitis C virus positive. To be listed, patients had to meet the following requirements. All patients received extensive psychosocial evaluations and were frequently monitored with random urine and blood alcohol tests; patients found positive were excluded or removed from the liver transplant waiting list. Detailed patient information was entered into a computerized database, and 36 discreet variables were analyzed in relation to success (patient listed and remained on the list) or failure (not listed or removed from the list based on noncompliance). RESULTS: Forty-nine patients were successfully listed. Nineteen received a transplant, with a 95% 1-year patient and graft survival rate and 21% alcohol relapse rate after transplantation. Twenty-two patients had either medical contraindication and/or died before transplant listing. Twenty-four patients were never listed and four were removed from the list due to recurrent alcoholism, for a total of 28 failures. Our statistical analysis identified five significant risk factors for failure: (I) living arrangement (alone/family versus community/friend), P=0.006; (II) history of suicide ideation, P=0.03; (III) history of previous alcohol-related hospitalization, P=0.01; (IV) lack of previous alcoholic rehabilitation before transplant evaluation, P=0.001; and (V) failure to accept further alcoholic rehabilitation before orthotopic liver transplantation, P=0.01. CONCLUSIONS: Our experience confirms that transplantation can be extremely successful in properly selected patients with alcoholic cirrhosis. We identified several predictive psychosocial factors of early alcoholic recidivism in transplant candidates.

Contraindications↗
PubMed2001

Structural consequences of metal complexation of cyclo[Pro-Phe-Phe-Ala-Xaa]2 decapeptides.

The conformational features of both free and Ca2+-complexed cyclo[Pro-Phe-Phe-Ala-Xaa]2 (with Xaa= Glu(OtBu), Lys(CIZ), Leu, and Ala) in solution have been determined by NMR spectroscopy and extensive distance-geometry calculations. The decapeptides are conformationally homogeneous in solution and show common structural features in their free and complexed forms. The structures of the free form contain only trans peptide bonds and are topologically similar to the structure of gramicidin-S, folded up in two antiparallel extended structures, stabilized by interstrand hydrogen bonds, and closed at both ends by two beta-turns. In contrast, the Ca2+-complexed peptides present two cis peptide bonds and are generally similar to those observed for the metal-complexed forms of antamanide and related analogues, folded into a saddle shape with two beta-turns. The Glu(OtBu)-, Leu-, and Lys(ClZ)-containing peptides examined here maintain the biological activity of the cyclolinopeptide A in their ability to competitively inhibit cholate uptake. The natural antamanide and cyclolinopeptide A are both able to inhibit the uptake of bile salts into hepatocytes. They share the same postulated active sequence Pro-Phe-Phe. Based on our structural results, we conclude that the ability to adopt a global conformation, characterized by a clear amphipathic separation of hydrophobic and hydrophilic surfaces, is an important feature for the functioning of this class of peptides.

Biological Transport↗
PubMed2001

Progressive functional adaptation of segmental bowel graft from living related donor.

We report a patient with short gut syndrome successfully treated with living related bowel transplantation. A 27-year-old Caucasian man was referred after traumatic loss of almost the entire bowel from the third portion of duodenum to the sigmoid colon. His HLA-identical sister volunteered as a donor. A 200-cm segment of ileum was successfully transplanted under tacrolimus-based immunosuppression. The posttransplant course was uneventful, without rejection or infectious complication. Total parenteral nutrition was discontinued 1 week posttransplant. At 6 months the patient had returned to his preinjury weight. Water and D-xylose absorption as well as fecal fat studies were markedly abnormal 1 month posttransplant but normalized by 6 months. The donor recovery was uneventful. A well-matched segmental ileal graft from living donor can provide complete rehabilitation for patients with short gut syndrome. We documented a progressive functional adaptation of the ileal graft, resulting in normal absorption by 5 months posttransplantation.

Adult↗