Biomedical subjects

C Croce

Publications and source records attributed to C Croce.

At least 19 recordsLinked to original sources

PubMed2005

Pancreas transplants from donors aged 45 years or older.

AIMS: Since donor age of 45 years or more is considered a relative contraindication for pancreas transplantation (PTx), we herein report our experience with these donors. METHODS: Pancreases from donors aged 45 years or older were used in 16 of 147 PTx procedures (11%). The final decision to accept a graft for PTx was based mainly on the quality of visceral perfusion and the gross appearance of the pancreas and the vessels. There were 9 men and 7 women, ranging in age from 45 to 55 years (average, 48.9 years) who were donors, due to cerebrovascular accidents (n = 11; 68.7%). Among the donor group, 5 patients were receiving multiple vasopressor agents (31.2%), and 2 had a history of cardiac arrest (12.5%). Pancreases were transplanted either simultaneously with a cadaveric kidney (n = 6) or as solitary grafts (n = 10). RESULTS: After a mean period of cold preservation of 616 minutes (range, 475 to 844 min), delayed endocrine function occurred in 1 recipient (6%), who subsequently achieved insulin independence. Two recipients died suddenly, with functioning grafts. Two further grafts were lost due to portal vein thrombosis (6%) or late arterial thrombosis (6%). Three patients required repeat surgery (18.7%). After a mean follow-up period of 26.6 months, actuarial 1-year and 5-year patient survival rates were 87.5%, with insulin independence in 81.2% and 67.7%, respectively. CONCLUSIONS: Meticulous donor selection and short preservation times allow the safe use of pancreases procured from donors aged 45 years or older, thus expanding the donor pool for PTx procedures.

Age Factors↗

PubMed2005

University of Wisconsin solution versus Celsior solution in clinical pancreas transplantation.

INTRODUCTION: This study compared the safety and efficacy of University of Wisconsin solution (UW) and Celsior solution (C) in pancreas transplantation (PTx). METHODS: A retrospective review of 154 PTx performed over a 61-month period included 77 grafts preserved with UW and 77 with C. The two groups were comparable for both donor and recipient characteristics. RESULTS: After a mean cold ischemia time of 624 minutes (range 360 to 945 minutes) for UW versus 672 minutes (range 415 to 1005 minutes) for C (P = NS), no primary endocrine nonfunction occurred. Delayed endocrine function was diagnosed in two grafts in the UW group (2.6%) versus none in the C group (P = NS). After a minimum follow-up of 4 months (mean 26.5 +/- 15.2 months), 22 recipients (UW = 11 vs C = 11; P = NS) required relaparotomy. Overall, 18 pancreata were lost due to either patient death with functioning graft (UW = 4 vs C = 1; P = NS) or graft loss due to other reasons (UW = 8 vs C = 5; P = NS). Actuarial 1- and 5-year patient survival rates were 93.5% and 86.8% for UW compared with 98.7% and 98.7% for C (P = .04). Actuarial graft survival rates at the same times were 88.3% and 75.0% for UW compared with 90.4% and 90.4% for C (P = NS). CONCLUSIONS: Within the range of cold ischemia times reported in this study, UW and C show similar safety and efficacy profiles for PTx.

Adenosine↗

PubMed2004

Kidney transplantation from donors aged more than 65 years.

BACKGROUND: There are no agreed criteria to predict the outcome of elderly donor kidneys or to decide between single (SKG) or dual (DKG) kidney graft transplantation. METHODS: Between January 1999 and January 2003, 46 SKG and 14 DKG were performed from elderly donors (mean donor age 71.6 years; range: 66 to 87). Kidney biopsies were scored according to Karpinski. A calculated admission creatinine clearance <50 mL/min and/or a biopsy score of 5 or 6 were used to select kidneys for DKG. Grafts with better function or lower biopsy scores were employed for SKG. RESULTS: Mean cold ischemia time (CIT) was 16.8 hours (range 8.1 to 28.6) in SKG, and 16.3 hours (range 4.6 to 24.3) for the first kidney and 17.4 hours (range 5.1 to 25.9) for the second graft in DKG. Delayed graft function (DGF) occurred in 34.1% SKG and in 28.5% DKG. Acute rejection rates were 9.1% for SKG and 0% for DKG. Three-year actuarial patient survival rates were 97.7% for SKG and 92.9% for DKG; for kidneys, 95.4% and 92.9%. One-year mean serum creatinine levels were 1.8 mg/dL (range 1.1 to 4.0) for SKG and 1.2 mg/dL (range 1.0 to 1.8) for DKG (P =.01). CIT longer than 16 hours was related to increased rates of DGF for both SKG (45.4% vs 22.7%) or DKG (42.9% vs 14.3%) and reduced 3-year graft survival rates (SKG: 90.9% vs 100%; DKG: 85.7% vs 100%). CONCLUSIONS: With stringent selection criteria and short CIT (<16 hours), elderly donor kidneys may show good results, thus meaningfully expanding the donor pool.

Age Factors↗

PubMed2004

Kidney and pancreas transplants in Jehovah's witnesses: ethical and practical implications.

Jehovah's Witnesses refuse blood transfusions but accept solid organ transplants. Six Jehovah's Witnesses received a kidney and/or a pancreas transplant in our center. After a mean follow-up of 31.4 months (range: 18 to 39) all the recipients are alive and well with functioning grafts. However, 1 month after grafting, one recipient required blood transfusions. Hemorrhage was ruled out and the anemia was attributed to drug-related toxicity. Thus, Jehovah's Witnesses can receive a kidney and/or a pancreas transplant without blood transfusions at the time of surgery. However, lifesaving transfusions may be needed later on, which raises additional and unique medical and ethical issues.

Adult↗

PubMed2004

Regional procurement team for abdominal organs.

BACKGROUND: The graft shortages make multiorgan procurements mandatory. We describe the results of a regional procurement team policy that has been employed over a 5-year period. METHODS: Three hundred forty-three multiorgan procurements were performed by a regional team using an en bloc harvesting method. RESULTS: Among 1374 grafts procured, none was discarded because of iatrogenic injuries. In three instances the liver, the pancreas, and the small bowel were procured simultaneously and transplanted to different recipients. In 42 instances the liver was not allocated to our center. Forty liver teams (95%) from 11 institutions agreed to allow the regional procurement team to run the donor procedure. CONCLUSIONS: Our experience confirms that a regional team can successfully manage most multiorgan procurements including complex donor procedures, such as simultaneous procurement of liver, pancreas, and intestine from the same donor for transplantation to different recipients.

Abdomen↗

PubMed2004

Pancreas preservation with University of Wisconsin and Celsior solutions.

BACKGROUND: Although the use of Celsior has been recently described for heart, lung, liver, and kidney transplantation, no data are available on its use for clinical pancreas preservation. METHODS: We herein describe the results of 112 pancreas transplants preserved with either University of Wisconsin (UW; (n = 56) or Celsior (n = 56) solution at two Italian transplant centers. The groups were comparable with regard to all donor and recipient characteristics. RESULTS: Mean cold and warm ischemia times were 10.1 +/- 2.2 hours and 37.2 +/- 8.2 minutes for UW compared to 10.8 +/- 2.4 hours and 38.3 +/- 6.7 minutes for Celsior (P = NS). Delayed endocrine pancreas function was recorded in two UW-preserved grafts (3.6%). Actuarial 1-year patient survival was 94.6% for UW as compared with 100% for Celsior (P = NS). Equivalent graft survival figures were 91.0% for UW as compared with 96.4% for Celsior (P = NS). CONCLUSIONS: Within the range of cold ischemia times reported in this study, UW and Celsior solutions have similar safety profiles for pancreas transplantation.

Adenosine↗

PubMed2004

Portal enteric-drained solitary pancreas transplantation without surveillance biopsy: is it safe?

BACKGROUND: Most solitary pancreas transplants (SPTx) fail due to unrecognized rejection episodes. Consequently, SPTx are monitored by drainage into the bladder or by surveillance biopsies. METHODS: Between April 2001 and June 2003, a consecutive series of 48 SPTx were performed using portal enteric drainage (PED). Rejection episodes were diagnosed empirically, based on the elevated pancreatic enzymes without a surveillance biopsy. Immunosuppression consisted of basiliximab (n = 42) or ATG (n = 6), low-dose steroids, MMF, and tacrolimus. Donors (mean age 28.9 year; range 9 to 54 year) were selected according to standard criteria irrespective of HLA match, although the best HLA matching was considered at the time of graft allocation. RESULTS: After a mean cold ischemia time of 676 minutes (range 475 to 900 minutes), all but two pancreata (95.8%) functioned immediately. Relaparotomy was required in seven cases (14.6%). Three grafts were lost in the early posttransplant period due to hyperacute rejection. Two additional grafts were lost later due to arterial thrombosis or to chronic rejection. After a median follow-up period of 12.2 months (range 0.2 to 27 months) three further recipients were diagnosed with rejection episodes that were reversed with steroid boluses. Actuarial 1-year patient and graft survival rates were 100% and 93.1% and 2-year figures 100% and 88.7%, respectively. At the longest follow-up no recipient was diagnosed with a malignancy. CONCLUSIONS: With current immunosuppression protocols SPTx achieves high rates of insulin independence even without surveillance biopsy or routine use of T-cell-depleting therapies.

Biopsy↗

PubMed2004

Single-center, open, prospective, randomized pilot study comparing cyclosporine versus tacrolimus in simultaneous pancreas-kidney transplantation.

BACKGROUND: Although tacrolimus (Prograf) is the calcineurin inhibitor usually employed in simultaneous pancreas-kidney transplantation (SPKTx), no prospective randomized studies have compared its efficacy to cyclosporine (Neoral), when either drug is used in combination with mycophenolate mofetil (MMF) and the pancreas is drained into the portal vein. METHODS: Between May 2001 and June 2003, 16 SPKTx recipients were randomized to be prescribed Neoral and 17 Prograf in addition to basiliximab, steroids, and MMF. All pancreata were drained into the portal vein. RESULTS: After a median follow-up of 15.6 months, six kidney acute rejection episodes were observed with Prograf (36.5%; one steroid-resistant) and one Neoral (n = 1, 6.2%; P =.04). No pancreas rejection episode was recorded. Two infections occurred in two recipients from each group. No major adverse events were noted other than a severe hematological toxicity (Prograf). Metabolic parameters were equivalent in the two groups, save for higher total cholesterol (212 +/- 39 mg/dL vs 173 +/- 23 mg/dL; P =.008), LDL (129 +/- 33 mg/dL vs 101 +/- 21 mg/dL; P =.029), and triglyceride (191 +/- 86 mg/dL vs 126 +/- 40 mg/dL; P =.028), values with Neoral, although the same differences were already present at baseline. One recipient (Neoral) died with functioning grafts. Patient, pancreas, and kidney survival rates were all 94% for Neoral versus 100% for Prograf. CONCLUSIONS: Although a larger series and a longer follow-up are needed, Neoral and Prograf used in combination with MMF seem to achieve equivalent success rates among primary SPKTx when the pancreas is drained into the portal vein.

Cyclosporine↗

PubMed2001

Clinical significance of fragile histidine triad gene expression in adult acute lymphoblastic leukemia.

The FHIT (fragile histidine triad) gene, which is located on 3p14.2 and believed to be a tumor suppressor gene, has been reported to lose its expression in several solid tumors and hematologic malignancies, including acute lymphoblastic leukemia (ALL). The clinical relevance of the loss of FHIT expression in ALL is not known. We used western blot and solid-phase radioimmunoassay (RIA) to analyze Fhit protein expression in 90 patients with ALL. Eighteen (20%) of the tested patients had severely reduced Fhit protein (undetectable by western blot), and 43 patients (47%) had levels lower than those detected in normal bone marrows. Interestingly, seven patients (8%) expressed very high levels (>two-fold the level detected in normal bone marrow). A parallel pattern of FHIT RNA expression was also observed. Of the 90 patients, 39 received induction therapy consisting of hyper-CVAD (hyperfractionated cyclophosphamide, vencristine, adriamycine, and dexamethasone) and were followed in our institution. Patients with low Fhit protein levels showed no statistically significant difference in survival or complete remission duration (CRD) from patients with normal levels (P=0.12 and 0.24, respectively). Our study confirms that FHIT is aberrantly expressed in ALL, but suggests it does not have a role as a prognostic factor. Studies with large numbers of patients and evaluation of the mechanisms of FHIT function in ALL are needed.

Acid Anhydride Hydrolases↗

PubMed1999

Cytogenetic profile of lymphoma of follicle mantle lineage: correlation with clinicobiologic features.

Conventional chromosome analysis (CCA) and interphase fluorescence in situ hybridization (FISH) was performed in 42 patients with mantle-cell lymphoma (MCL), with BCL1 rearrangement. The t(11;14)(q13;q32) or 11q abnormalities were detected by CCA in 34 cases, 20 of which had additional aberrations. A normal karyotype was observed in 8 cases. Probes detecting the chromosome aberrations that were observed in at least 3 cases by CCA, ie, +12, 13q14 deletion, and 17p deletion, were used for interphase FISH analysis. FISH detected total or partial +12, 13q14 deletion and 17p- in 28.5%, 52.4%, and 26% of the cases, respectively. The presence of these anomalies was not a function of karyotype complexity. Based on the results of CCA/FISH, three groups of increasing karyotype complexity were recognized: group 1, including 11 patients without detectable aberrations in addition to BCL1 rearrangement; group 2, including 14 patients with 1 to 2 additional anomalies; and group 3, including 17 patients with three or more additional anomalies. Clinical parameters associated with shorter survival were male sex (P =.006) and primary lymph-node involvement compared with primary bone marrow involvement (P =.015). Trisomy 12 was the only single cytogenetic parameter predictive of a poor prognosis (P =.006) and the best prognostic indicator was the derived measure of karyotype complexity (P <.0001), which maintained statistical significance in multivariate analysis (P<.0001). We arrived at the following conclusions: 13q14 deletion occurs at a high incidence in MCL; 17p deletion and total/partial +12 are relatively frequent events in MCL, the latter aberration being associated with a shorter survival; and the degree of karyotype complexity has a strong impact on prognosis in this neoplasia.

Adult↗

PubMed1999

13q14 deletion in non-Hodgkin's lymphoma: correlation with clinicopathologic features.

BACKGROUND AND OBJECTIVE: 13q14 deletion frequently occurs as a single anomaly in chronic lymphocytic leukemia (CLL) with favorable prognosis. This study was performed to assess the distribution of 13q14 deletion in non-Hodgkin's lymphoma (NHL) and to analyze its correlation with salient clinicopathologic features. DESIGN AND METHODS: One hundred and twenty-five NHL were analyzed by cytogenetics and by interphase fluorescence in situ hybridization (FISH), using a 13q14 cosmid probe recognizing DNA sequences between the Rb gene and the D13S25 marker. Clinical records all patients were surveyed. RESULTS: A 13q14 rearrangement was present in the stemline in 10 patients; 15 additional cases were shown by FISH to carry 13q14 deletion in 55-90% of the interphase cells, giving a 20% overall incidence for this anomaly. Six of 44 patients had a low-grade NHL, 14/28 had mantle cell lymphoma (MCL), 5/42 had a high grade NHL (p<0.0001). There was not correlation between 13q, karyotype status and complexity. A statistically significant association was found between 13q-, presence of splenomegaly and PB involvement, lower probability of attaining complete remission (CR) and shorter survival. These findings were not simply a function of the association of 13q- with MCL. In multivariate analysis, a complex karyotype had prognostic importance (p=0.0078), along with age (p=0.01), histology (p=0.001), LDH (p=0.03), PS (p=0.001), sex (p=0.03) and splenomegaly (p=0.02). INTERPRETATION AND CONCLUSIONS: 13q14 deletion represented an early chromosome change and showed a preferential association with MCL, though it was found in virtually all principal histologic subtypes, irrespective of clinical stage, karyotype status and complexity. Patients with 13q14 deletions had a low CR rate, suggesting that genes relevant to lymphomagenesis are located in this chromosome segment that warrants molecular cytogenetic investigation.

Biomarkers, Tumor↗

PubMed1996

Identification of AF-6 and canoe as putative targets for Ras.

Ras (Ha-Ras, Ki-Ras, N-Ras) is implicated in the regulation of various cell functions such as gene expression and cell proliferation downstream from specific extracellular signals. Here, we partially purified a Ras-interacting protein with molecular mass of about 180 kDa (p180) from bovine brain membrane extract by glutathione S-transferase (GST)-Ha-Ras affinity column chromatography. This protein bound to the GTP gamma S (guanosine 5'-(3-O-thio)triphosphate, a nonhydrolyzable GTP analog).GST-Ha-Ras affinity column but not to those containing GDP.GST-Ha-Ras or GTP gamma S.GST-Ha-Ras with a mutation in the effector domain (Ha-RasA38). The amino acid sequences of the peptides derived from p180 were almost identical to those of human AF-6 that is identified as the fusion partner of the ALL-1 protein. The ALL-1/AF-6 chimeric protein is the critical product of the t (6:11) abnormality associated with some human leukemia. AF-6 has a GLGF/Dlg homology repeat (DHR) motif and shows a high degree of sequence similarity with Drosophila Canoe, which is assumed to function downstream from Notch in a common developmental pathway. The recombinant N-terminal domain of AF-6 and Canoe specifically interacted with GTP gamma S.GST-Ha-Ras. The known Ras target c-Raf-1 inhibited the interaction of AF-6 with GTP gamma S.GST-Ha-Ras. These results indicate that AF-6 and Canoe are putative targets for Ras.

Amino Acid Sequence↗

PubMed1994

In vitro and in vivo impact of a new glycosphingolipid on neutrophils.

A new water-soluble, orally absorbable de-N-acetyl-lysoganglioside (WILD20), breakdown product of the monosialoganglioside GM1, was found to influence some parameters of neutrophil response to inflammation stimuli. Superoxide anion production appears inhibited, along with neutrophil killing properties. A block of both pathways of arachidonic acid cascade and PAF was also found, as well as neutrophil ICAM-1-mediated adhesion to endothelial cells. Of particular interest was the significant reduction of neutrophils observed at the site of inflammation, whichever agonist was used. The effects on neutrophil physiology found in normal or in pathological conditions, are in favour of a WILD20-related inhibitory effect on neutrophil contribution to inflammation.

Animals↗

PubMed1993

Antiplatelet effects of a new de-N-acetyl-lyso-glycosphingolipid.

Gal beta 1-->3GalN beta 1-->4Gal(3<--2 alpha Neu)beta 1-->4Glc beta-->1Sph (WILD20), a new glycosphingolipid, a breakdown product of the monosialoganglioside GM1 obtained through alkaline hydrolysis, shows dose-dependent platelet anti-aggregating properties in vitro and in vivo. This effect is agonist- and species-independent. The family of lysosphingolipids, to which the compound belongs, is present in platelets particularly after thrombin treatment. WILD20 antiplatelet effect is due to the interference with ADP or thrombin-induced aggregation, probably via phospholipase A2 (PLA2) blockade; the substance is also effective when arachidonic acid is used as an agonist. Serotonin blood levels are also reduced. The substance, orally active at dosages of 0.1-0.01 mg/kg as antiplatelets agent, prolonged bleeding time without interfering with the coagulative or fibrinolytic processes.

Animals↗

PubMed1993

Effect of a new de-N-acetyl-lysoglycosphingolipid on chemically-induced inflammatory bowel disease: possible mechanism of action.

A new, orally active de-N-acetylated lysoglycosphingolipid (WILD20) was evaluated as antiinflammatory agent using a model of chemically-induced inflammatory bowel disease (IBD) in the rat to mimic human ulcerative colitis and Chron's disease. IBD was induced by hapten trinitrobenzenesulphonic acid (TNB). WILD20, orally administered as preventive or curative, was demonstrated to be efficacious at daily dosages of 0.1-1 mg/kg for 4-5 days. Damage scores, body weight, spleen weight, colonic tissular levels of LTB4, myeloperoxidase (MPO) and malondialdehyde (MDA) are influenced and brought into parameters of normality. Histological observation demonstrated quicker healing, better repair, reduced inflammation, and poor eosinophil degranulation. The mechanisms underlying WILD20 antiinflammatory effects were investigated: whereas WILD20 fails to show a direct effect on PKC, it reduces PKC translocation to the membrane; cellular PLA2 was consequently greatly reduced through this mechanism and thought to be responsible for WILD20 efficacy towards chemically-induced IBD.

Animals↗

PubMed1991

cDNA cloning and chromosomal localization of the human beta-adrenergic receptor kinase.

The beta-adrenergic receptor kinase (beta ARK) mediates agonist-dependent phosphorylation of the beta 2-adrenergic and related G protein-coupled receptors. A cDNA encoding bovine beta ARK has recently been isolated. In this work we have isolated a cDNA encoding human beta ARK from a retinal cDNA library. The cDNA encodes a protein of 689 amino acids with an overall 98.0% amino acid and 92.5% nucleotide identity with bovine beta ARK. Chromosomal location of the human beta ARK gene was determined by correlating the presence of the beta ARK locus with retention of a specific human chromosome in a rodent-human hybrid panel. This analysis revealed that the human beta ARK locus segregated with the long arm of chromosome 11, centromeric to 11q13.

Amino Acid Sequence↗

PubMed1991

Relationship of the human protooncogene CBL2 on 11q23 to the t(4;11), t(11;22), and t(11;14) breakpoints.

A probe identifying CBL2, the human cellular homolog of the murine oncogene v-cbl and murine cellular protooncogene Cbl-2, and panels of rodent X human somatic cell hybrids were used to study the relationship of this protooncogene to translocations associated with acute leukemia, lymphoma, and Ewing sarcoma. CBL2 was mapped to 11q23 and found to translocate from chromosome 11 to 4 in an acute leukemia cell line possessing a t(4;11)(q21;q23) and from chromosome 11 to 14 in a B-cell lymphoma with a t(11;14)(q23;q32). In an Ewing sarcoma cell line with a t(11;22)(q23;q12), however, CBL2 remained on chromosome 11. Additional studies of other genes in the region of 11q23 allowed the following ordering of these genes and breakpoints: 11cen--q23--NCAM--CD3(E-D-G)--[t(11;14), t(4;11)]--(THY1, CBL2, ETS1)--t(11;22)--11qter. The gross structure of the CBL2 sequences examined was not altered by either of the flanking breakpoints. Given that the 5' and 3' ends of the CBL2 gene are not known and are probably not evaluated by the v-cbl probe, these results do not rule out the possibility of CBL2 involvement in the pathogenesis of a subset of acute leukemias possessing a t(4;11), B-cell lymphomas possessing a t(11;14), or Ewing sarcomas possessing a t(11;22).

Animals↗

PubMed1991

Germ line configuration of the BCL-2 major breakpoint region in hyperplastic lymph nodes.

The configuration of the BCL-2 major breakpoint region was analyzed by Southern blot hybridization and polymerase chain reaction amplification in DNA derived from 44 benign hyperplastic lymph nodes with follicular overgrowth. None of the cases exhibited translocation of the BCL-2 gene at the major breakpoint region of chromosome 18. The potential usefulness of molecular genetic detection of BCL-2 translocation in the differential diagnosis between hyperplastic lymph nodes and lymphomas is suggested.

Base Sequence↗