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Biomedical subjects

J Cicciarelli

Publications and source records attributed to J Cicciarelli.

At least 19 recordsLinked to original sources
PubMed2006

Expanding the donor kidney pool: utility of renal allografts procured in a setting of uncontrolled cardiac death.

The chronic shortage of deceased kidney donors has led to increased utilization of donation after cardiac death (DCD) kidneys, the majority of which are procured in a controlled setting. The objective of this study is to evaluate transplantation outcomes from uncontrolled DCD (uDCD) donors and evaluate their utility as a source of donor kidneys. From January 1995 to December 2004, 75,865 kidney-alone transplants from donation after brain death (DBD) donors and 2136 transplants from DCD donors were reported to the United Network for Organ Sharing. Among the DCD transplants, 1814 were from controlled and 216 from uncontrolled DCD donors. The log-rank test was used to compare survival curves. The incidence of delayed graft function in controlled DCD (cDCD) was 42% and in uDCD kidneys was 51%, compared to only 24% in kidneys from DBD donors (p < 0.001). The overall graft and patient survival of DCD donors was similar to that of DBD donor kidneys (p = 0.66; p = 0.88). Despite longer donor warm and cold ischemic times, overall graft and patient survival of uDCD donors was comparable to that of cDCD donors (p = 0.65, p = 0.99). Concerted efforts should be focused on procurement of uDCD donors, which can provide another source of quality deceased donor kidneys.

Adult↗
PubMed2005

Renal biopsy donor group: the influence of glomerulosclerosis on transplant outcomes.

The UNOS donor population was examined from 1999 to 2002, and approximately 25% of the over 23,000 donors were biopsied (Bx). There was a significant trend (P < .001) of older donors, cardiovascular accident, and hypertension in the Bx group versus the non-Bx group. The percent GS was directly correlated (P < .001) to graft survival, delayed graft function, and primary nonfunction. Cox regression showed significant relative risk (RR) for >10% GS, hypertension, donors over the age of 50, and African American recipients. RR in donors with >10% GS could be ameliorated (P < .001) by choosing donors with <5 HLA-A, -B, or -DR mismatches (MM), or recipients who were nonsensitized, and/or first transplant. Risk should be managed in donors by choosing appropriate recipients and high-risk immunosuppresion protocols.

Adult↗
PubMed2005

Significant HLA matching effect in a large urban transplant center composed primarily of minorities.

In more than 1300 deceased donor transplants, including 75% Hispanics, African-Americans, and Asians, a significant effect of mismatching (MM) was observed for zero to three MM compared to more than three MM (P < .02). There was a significantly better patient survival (P < .002), shorter hospital stay (P < .001), and a trend toward lowered immunosuppression. Zero to three MM were present in 48% of the recipient population in part due to the pre-UNOS algorithm that assigns points for zero MM and other MM grades. However, recently only zero MM receive points, therefore fewer zero to three MM recipients would be expected. The largest minority population is Hispanic. We postulated that at least part of the effect was associated with socioeconomic status and English as a second language parameters of our Hispanic population. Zero to three MM was found to decrease risk and should be used prospectively in minority donor/recipient combinations.

ABO Blood-Group System↗
PubMed2004

Multiplexed analysis of polymorphisms in the HLA gene complex using bead array chips.

A novel custom bead array technology is introduced, and it is applied to multiplexed analysis of highly polymorphic human leukocyte antigen (HLA) genetic loci. Our technology combines the construction of probe libraries on color-encoded microparticles (beads) with semiconductor chip processing to produce custom-designed high-density bead array chips in large quantities. Using this novel assay format, two modes of parallel molecular typing of the HLA complex were implemented, namely direct hybridization, illustrated here for class II HLA-DR, and a novel format of on-chip polymerase-mediated primer elongation, illustrated here for class I HLA-A, HLA-B, and HLA-DR using patient and reference cell-line DNA samples. Hybridization-mediated multiplexed analysis of polymorphism method was validated with 142 samples, resulting in 100% concordance with sequence-specific oligonucleotide typing results and a concomitant average of 40% less allele ambiguity. In addition, elongation and hybridization reactions were combined to identify multiple polymorphisms on the same phase of DNA for allele identification.

HLA Antigens↗
PubMed1999

The influence of donor age on kidney graft survival in the 1990s.

Based on analyses of the UNOS Registry data for cadaver kidney transplants performed between 1991-1999 we showed that: 1. 15-40 year old donor kidneys provided the best one-year graft survival rates. When donors were analyzed with recipients, younger (0-10) and older (70-90) donors and recipients (Table 2) had the lowest one-year graft success rates. 2. Chronic loss rate, the constant rate of graft loss between one and 5 years, showed younger donor kidneys had a significantly lower chronic loss rate compared with each older donor category. Apparently the younger donor kidneys have a resiliency and nephron reserve that provides better long-term function. However, they may have lower short-term (1-yr) graft survival rates, possibly due to their small size. 3. Black and White donor kidneys had similar one-year graft survival rates; however, in every age group, recipients of White donor kidneys had significantly better 5-year graft survival rates than Black donor kidneys. There was also a noticeably lower chronic loss rate among recipients of White than Black donor kidneys. 4. HLA-matched White donor kidneys had better one- and 5-year graft survival rates and lower chronic loss rates than HLA-mismatched kidneys. The matching effect was lost when the donor age increased beyond age 40. PRA had an effect both at one and 5 years after transplantation. The chronic loss rate was similar with high and low PRA. Therefore, PRA had a relatively short-term effect. 5. Cold ischemia time had a modest effect after 35 hours both at one and 5 years. However, the chronic loss rate was unaffected by CIT, suggesting prolonged ischemia time had a relatively short-term effect. 6. More focused attention on sensitization and lowered CIT can both have a significant effect on short-term graft survival rates. However, both matching and younger donor organs provide the best opportunity for better long-term graft success rates.

Adolescent↗
PubMed1996

BCX-34: a novel T-cell selective immunosuppressant: purine nucleoside phosphorylase (PNP) inhibitor.

We evaluated the efficacy of a new purine nucleoside phosphorylase inhibitor, BCX-34, as an immunosuppressive agent. BCX-34 showed a complete inhibitory effect on the proliferation of T-cells in an in vitro system, whereas no influence was observed in B-cell lines. In addition, it was revealed that this inhibitory effect was not due to the suppression of interleukin-2 production. Therefore, BCX-34 might be a potentially useful drug that can be used in combination, not competition, with cyclosporine A and FK506.

Animals↗
PubMed1992

Flow cytometry PRA, a new test that is highly correlated with graft survival.

IgM antibodies present in the recipient sera are not necessarily harmful to the outcome of the graft. However, one primarily measures IgM with panel-reactive antibody (PRA) determined by microcytotoxicity. In order to develop a potentially more correlative PRA measurement, we have utilized the flow cytometer to measure IgG antibody to a panel of lymphocytes representing HLA antigens. This was accomplished by measuring the median channel shift associated with the patient's serum antibody binding to pooled target cells. The correlation between flow PRA and graft outcome was analyzed in 59 regraft recipients using current serum prior to transplantation. The PRA was determined by both cytotoxicity and flow cytometry. One-year follow up was available on all transplant recipients with 62% 1-yr actuarial graft survival. Cytotoxic PRAs were divided into greater than 10% and less than or equal to 10%, with a 72% vs 70% graft survival at 6 months and 62% vs 62% 1 yr graft survival, respectively. Flow cytometry PRA was divided into greater than 10 and less than or equal to 10 channel shift with 63% vs 86% graft survival at 6 months, and 53 vs 79% 1 yr graft survival respectively (p less than 0.05 for both time intervals). Serum creatinine levels were concomitantly lower at 1 and 3 months in the flow PRA-negative recipients. Flow PRA was a simple, rapid test which eliminates "false" positives due to IgM and detects non-complement fixing IgG, which occurred in 25% of the samples.(ABSTRACT TRUNCATED AT 250 WORDS)

Cytotoxicity Tests, Immunologic↗
PubMed1991

HLA matching at a single kidney transplant center.

Over 1000 patients were analyzed in two different time intervals, 1978-1983 and 1984-1989; these corresponded to patient groups not treated with cyclosporine and treated with cyclosporine. Analysis of mismatching showed that there was a significant (P less than 0.05) longterm matching effect in the precyclosporine, era with 0 HLA-DR-mismatched recipients having a 9.5-year half-life compared with a 3-year half-life for the 2 HLA-DR-mismatched transplant recipients. The trend was similar for the cyclosporine-treated groups, but not significant. Risk factors for donor age and race of the recipient (P less than 0.05) were identified in the cyclosporine-treated group. Graft survival in the high-risk patient populations was 70% or better in the 0, 1 HLA-ABDR-mismatched groups as compared with less than 60% graft survival in the high-risk transplant recipients with 2-6 HLA-ABDR mismatches. In the cyclosporine era the HLA-ABDR 0, 1-mismatched patient groups showed a significantly better graft survival than was found in all other categories and at all time intervals analyzed. Matching is a way to ameliorate some of the high risk potential associated with less than optimal donor or recipients.

Age Factors↗