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Biomedical subjects

J Cicciarelli

Publications and source records attributed to J Cicciarelli.

At least 19 recordsLinked to original sources
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↗
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↗
PubMed1991

HLA matching: univariate and multivariate analyses of UNOS Registry data.

1. Black transplant recipients showed little or no matching effect when HLA-A, B, and DR antigens matched. This may have been due in part to differences in serologically defined antigens found in Black populations. 2. There was a statistically significant (p less than 0.001 for best vs worst match) matching effect in White transplant recipients that occurred at 3 months following grafting and continued through 3 years follow-up. These patients had better graft survival for both 5 and 6, compared to 3 and 4, or as compared to 0-, 1-, and 2-match transplants; the corollary groups for mismatched transplants were also significantly different. At 3 years, there was a 20% difference in graft survival from the best- to the worst-matched transplants. Earlier this difference was 7-10% but significantly different. 3. When the HLA Class I parent antigens as defined in the Materials and Methods section were eliminated, there was an increase in graft survival for the best-matched transplants. This was postulated to occur because of better matching obtained by matching the well-defined HLA specificities. 4. With hierarchy matching, possibly there was a stronger effect of matching HLA Class II antigens at 3 months; however, this effect was quickly lost at 1 and 3 years, and data that support early graft survival advantages by matching Class II antigens were inconclusive. Most importantly, there was a threshold matching effect that showed transplant recipients with 4 or more HLA matches or 2 or less mismatches had significantly better short- and long-term outcome than the poorer-matched groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

UNOS Registry data: effect of transfusions.

1. First cadaver White transplant recipients had a 4-5% increase in graft survival associated with transfusions compared with nontransfused recipients (p less than 0.001). The effect, although small, was significant, occurred at 3 months, and was evident at 1 year. This early effect (3 months) was also noted in regraft transplant recipients, living-related recipients, and 1-haplotype match transfused patients. 2. African-American and Hispanic transplant recipients did not show a transfusion effect. Indeed, African-American transplant recipients showed a reverse transfusion effect, which is in contrast to other previously reported UCLA Registry data. 3. The effect of during-transplant transfusions was negligible (ie, a 1% increase in graft survival). Additionally, one-fourth of all recipients had perioperative transfusions. 4. A transfusion effect was not shown within HLA matching for Class I antigens; similarly, little transfusion effect was found within matching groups for Class II antigens. Again, this contrasts with reported UCLA Registry data which indicated that the transfusion effect had a 10-15% difference in graft survival between the non- and transfused individuals in the 2-mismatch HLA Class II antigen group. 5. One of the most important effects on graft survival is donor age, and the preliminary data indicate that transfusions may help graft function in recipients of older donor kidneys. However, there are very few recipients in this older donor category. 6. The incidence of graft rejection was lower in transfused recipients. Additionally, graft rejection episodes remain a very potent indicator of transplant survival. That is, patients having graft rejection at 3 months showed a 20-25% lower 1-year graft survival rate than those without rejection. There were indications that there was less severe graft rejection in transfused patients; however, this could only be shown if graft rejection occurred at discharge and was not evident at 3 months or 6 months posttransplant. 7. SCr was the best indicator of 1-year graft function, even better than the presence or absence of rejection. Lower SCr levels were found in higher frequency in transfused patients. 8. There was a slight increase in graft survival associated with transfusion and PRA in first-transplant recipients, and in the PRA-positive and PRA-negative groups, there was a trend toward lower graft survival for recipients with antibodies. In regrafts, transfused recipients who did not make antibodies had a 5-10% better graft survival than the nontransfused recipients without antibodies. Perhaps this indicates that transplant candidates who did not make cytotoxic antibodies after being transfused were nonresponders.(ABSTRACT TRUNCATED AT 400 WORDS)

Age Factors↗
PubMed1989

Clinical kidney transplants, 1988.

1. The one-year graft survival rate of cadaver donor transplants has increased from about 40% in 1965 to almost 80% in 1988. Much of the improvement lies in the reduction of the one-month failure rates, which went down from one quarter in 1965 to 10% in 1988. 2. Kidneys that failed to function in the first month occurred in 5% of first graft patients without cytotoxins and increased to 9% if cytotoxins to more than 50% of the random panel were present. The non-function rate was 9% in regrafted patients without antibodies and double (18%) in those with a PRA of less than 50%. 3. Some indication that the harmful antibodies can be detected by flow cytometry is provided by the fact that low graft survival rates resulted when transplants were done across a positive flow cytometry crossmatch in sensitized patients and in second graft recipients. In non-sensitized patients and in first graft patients, flow cytometry crossmatches against T cells were of no value. 4. The difference between first grafts, second grafts and transplants into sensitized patients disappeared when the grafts that did not function at one month were removed. 5. Cold ischemia time up to 36 hours had no effect on 1-3-year survival rates. Cold ischemia had relatively little effect even on delayed function in first transplants. However, in regrafts and in grafts into patients with preformed cytotoxins, increasing cold ischemia resulted in an increased incidence of delayed function.(ABSTRACT TRUNCATED AT 250 WORDS)

Graft Survival↗
PubMed1989

Overview and epitope matching.

1. Kidney graft survival rates have stabilized over the past 4 years, suggesting that gains achieved with CsA have plateaued. The overall 1-year graft survival is 77% for first cadaver donor transplants, 90% for parental donors, and 93% for HLA-identical sibling donors. Patient survival for all categories is now over 95%. 2. The UNOS 6-antigen match program has resulted in outstanding graft survivals. Of 88 kidneys which were transplanted into first graft recipients, the 6-antigen match kidney had a 1-year graft survival of 91% compared to 74% for the contralateral kidney transplanted locally (p less than 0.008). 3. In highly sensitized patients with more than 80% PRA the shipped 6-antigen matched kidney had a 91% 1-year graft survival rate compared to 72% survival in comparable control patients from the registry (p less than 0.005). In patients with less than 80% PRA, 6-antigen matched kidneys had 90% 1-year graft survival compared to 80% in controls (p less than 0.00001). 4. The spread of 1-year graft survival rates at 68 centers that performed more than 100 transplants was 63-94%. The cumulative graft survival of 6-antigen matches performed at 129 different centers was 90%. Thus, the strong center effect was neutralized by the use of matched transplants. 5. In contrast to the 1% of patients who would receive O-B,DR mismatched transplants on a random basis, if kidneys were shared in the national pool, 74% could receive such a transplant. We therefore propose that a keep one-share one policy be adopted for all kidneys harvested in the United States. If no 0-B,DR mismatched patient is available, both kidneys will be kept by the harvesting center. Since 63% of kidneys are currently being shared with other centers for various reasons, the 75% sharing suggested by the new system should not impose a hardship on transplant centers. The UNOS payback agreement will be replaced by this agreement by which shipping will be done only to achieve excellent matches. 6. In order to achieve a better method of excluding the worst mismatches, an attempt was made to develop a new method of mismatching using amino acid sequences of the HLA specificities. Donor and recipient types can be converted to amino acid sequences and the mismatching done on the basis of amino acids of mismatch at each residue or position. For each residue, specific combinations of amino acid substitutions were examined individually to determine their effect on graft survival. From these studies, a list of "immunogenic" amino acids was prepared, and graft survival was then computed for increasing numbers of amino acids of mismatch.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗