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S Katznelson

Publications and source records attributed to S Katznelson.

28 records · Page 2Linked to original sources
PubMed1996

Immunosuppressive regimens and their effects on renal allograft outcome.

The distribution and effectiveness of different immunosuppression protocols among recipients of first cadaver donor renal transplants reported to the UNOS Scientific Renal Transplant Registry whose graft survived at least 14 days after transplantation were analyzed. The results showed that between 1988-1993, 50-60% of recipients received triple therapy regimens including cyclosporine, azathioprine and prednisone (CAP). An additional 20% received CAP with antibody induction therapy (OKT3 or ALG). After 1993, there was an increase in the use of other drug combinations which include FK506 and, more recently, Neoral and mycophenylate mofetil. Patient survival was 90% at 3 years regardless of the immunosuppressive protocol. The 3-year graft survival rate was 75% under cyclosporine-based protocols, but was 79% for more recent recipients treated with FK506 (p = 0.015). Antibody induction protocols were not used more frequently for high-risk patients, including those with broadly reactive anti-HLA antibodies, pediatric recipients, transplants with delayed graft function and those with prolonged cold ischemia times. When induction therapies were reported for these higher risk transplants, there was no noticeable improvement in graft survival rates after excluding failures within the first 2 weeks. Any benefit of antibody induction must therefore be manifest with the first 2 weeks after transplantation. Induction protocols significantly reduced the incidence of rejection episodes (prior to hospital discharge) from 31% for those treated with CAP to 12% for those with antibody induction (p < 0.01), however, 24% of those given induction had at least one rejection between discharge and 6 months compared with only 18% of those treated with CAP without induction (p < 0.01). Although graft outcomes might be significantly influenced by the dosing and timing of immunosuppressive drugs, among the different combinations of drugs analyzed, only FK506 resulted in improved graft survival and half life. With the rapid proliferation of newer drugs and immunosuppressive strategies during 1996, it will be interesting to follow the course of these very recent transplants with regard to the effectiveness of changing immunosuppression.

Cadaver↗
PubMed1995

Effect of pravastatin on outcomes after cardiac transplantation.

BACKGROUND: Hypercholesterolemia is common after cardiac transplantation and may contribute to the development of coronary vasculopathy. Pravastatin, a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, has been shown to be effective and safe in lowering cholesterol levels after cardiac transplantation. Cell-culture studies using inhibitors of HMG-CoA reductase have suggested an immunosuppressive effect. METHODS: Early after transplantation, we randomly assigned consecutive patients to receive either pravastatin (47 patients) or no HMG-CoA reductase inhibitor (50 patients). RESULTS: Twelve months after transplantation, the pravastatin group had lower mean (+/- SD) cholesterol levels than the control group (193 +/- 36 vs. 248 +/- 49 mg per deciliter, P < 0.001), less frequent cardiac rejection accompanied by hemodynamic compromise (3 vs. 14 patients, P = 0.005), better survival (94 percent vs. 78 percent, P = 0.025), and a lower incidence of coronary vasculopathy in the transplant as determined by angiography and at autopsy (3 vs. 10 patients, P = 0.049). There was no difference between the two groups in the incidence of mild or moderate episodes of cardiac rejection. In a subgroup of study patients, intracoronary ultrasound measurements at base line and one year after transplantation showed less progression in the pravastatin group in maximal intimal thickness (0.11 +/- 0.09 mm, vs. 0.23 +/- 0.16 mm in the control group; P = 0.002) and in the intimal index (0.05 +/- 0.03 vs. 0.10 +/- 0.10, P = 0.031). In a subgroup of patients, the cytotoxicity of natural killer cells was lower in the pravastatin group than in the control group (9.8 percent vs. 22.2 percent specific lysis, P = 0.014). CONCLUSIONS: After cardiac transplantation, pravastatin had beneficial effects on cholesterol levels, the incidence of rejection causing hemodynamic compromise, one-year survival, and the incidence of coronary vasculopathy.

Cholesterol↗
PubMed1995

HMGCoA reductase inhibitors and omega-3 fatty acids as adjunctive agents in maintenance immunosuppression after solid organ transplantation.

Omega-3 fatty acids have been shown to play a role in preventing development of both acute and chronic rejection. New evidence also suggests that HMGCoA reductase inhibitors may have an immunomodulatory effect and may decrease the incidence of rejection in both animal and human transplant models. Omega-3 fatty acids and HMGCoA reductase inhibitors may be important adjunctive agents in improving short-and long-term allograft function.

Adjuvants, Immunologic↗
PubMed1995

Dual roles of HMG-CoA reductase inhibitors in solid organ transplantation: lipid lowering and immunosuppression.

Hyperlipidemia has been associated with the development of transplant coronary vasculopathy (TCV) in heart transplant recipients and chronic rejection in kidney transplant recipients. HMG-CoA reductase inhibitors (HMGCoARIs) are effective in treating post-transplant hyperlipidemia, but their effects on patient and graft outcome remain unclear. In a prospective randomized trial investigating pravastatin (PVS) use early after heart transplantation, we observed that PVS treated patients had a decreased incidence of clinically severe acute rejection episodes resulting in a significant improvement in one year survival (94% vs. 78% in the control group, P = 0.02), and decreases in both the incidence and progression of TCV. This observation was validated in a prospective randomized study of kidney transplant recipients where we found that PVS reduced the incidence of acute rejection episodes (25% vs. 58% in the control group, P = 0.01). In both the heart and kidney transplant recipients, taking PVS, we noted decreases in natural killer cell (NKC) cytotoxicity. In vitro studies reveal that: PVS inhibits NKC cytotoxicity; PVS acts synergistically with cyclosporine to inhibit cytotoxic lymphocyte activity; and, other HMGCoARIs inhibit T-cell proliferation and monocyte chemotaxis. In conclusion, HMGCoARIs may have immunosuppressive properties in transplant recipients that could be useful in combating acute and chronic rejection.

Animals↗
PubMed1995

The effect of race and ethnicity on kidney allograft outcome.

Asian recipients of cadaveric renal allografts had the best long-term survival rates. Five-year graft survival rates were 66% for 1,713 Asians, 61% for 4,722 Hispanics and 33,190 Whites, and 47% for 12,948 Blacks. This trend had already been established at one-year posttransplant. Transplant half-lives calculated after 6 months were 12 years for Asians, 10 years for Whites, 9 years for Hispanics and 5 years for Blacks. These have all improved over the last 4 years. Part of the explanation for the outstanding half-life for Asian recipients is the 15 year half-life of the 672 Asian females reported. The superior graft survival for Asian recipients may be due in part to the low incidence of sensitization, the low incidence of acute rejection and chronic rejection leading to graft loss, and the high prevalence of primary disease entities that have been associated with excellent long-term prognoses, especially IgA nephropathy and chronic glomerulonephritis. Hispanic recipients also had excellent short- and long-term graft survival rates. This may be due to having the lowest incidence of early acute rejection episodes compared with all other racial groups, and the limited deleterious effect of ATN on long-term graft survival among Hispanics. The poor overall graft survival for Black recipients may be due to poor HLA matching, a high rate of sensitization and a grim effect of sensitization on graft survival, the high incidences of acute rejection and ATN, and the high incidence of HTN both pre- and posttransplant. The only subgroups of Black recipients who had graft survival rates that were comparable to other racial groups were the zero-HLA-mismatched Black recipients and those Black recipients over age 65. Long-term patient survival rates were the best for Asians and Hispanics (89% and 90% at 5 years, respectively). The 5-year patient survival rates were lower for Blacks and Whites (86% each). There was no difference in patient survival at one-year posttransplant (95-96% for each group). A higher proportion of White diabetic recipients received simultaneous SPK transplants (31%) than Black (10%), Hispanic (11%) or Asian (7%) diabetics. The reasons for this disparity are unclear. However, SPK transplants improved 5-year kidney graft survival for Whites (67% vs 55% in patients receiving kidneys alone), but were not associated with improved 5-year kidney survival among non-Whites. White donors accounted for the majority of all transplanted organs (79%). Matching donor and recipient race ("race matching") led to better long-term allograft survival for White recipients only. There was no donor-recipient "race matching" effect for minority groups.

Adolescent↗
PubMed1994

Primary disease effects and associations.

1. Although graft survival for most primary disease processes are similar at one year, significant divergence occurs by 5 years. ALP, IGA, and PC had the highest 5-year graft survival rates (72.8%, 71.2%, and 68.5%, respectively) whereas HTN and NS, the lowest (51.8% and 46.0%, respectively). 2. When primary diseases are grouped by pathogenic, pathophysiologic, and clinical similarities, the group of diseases with systemic manifestations had the lowest 5-year graft survival (55%), and the group including cystic and inherited diseases had the highest 5-year graft survival (69%). Black recipients had a predominance of "systemic" primary diseases (57%). 3. Despite having overall lower graft survival than Whites (p < 0.00001), there was no significant difference between Black and White 3-year graft survival for recipients with PC, ALP, IGA, and SLE. 4. PC recipients enjoyed excellent long-term graft survival (69%). Black recipients with PC had a 5-year graft survival rate of 64.6%. Recipients with PC had decreased posttransplant dialysis need, decreased early rejection rate, and better HLA matching than most other recipients. 5. Recipients with SLE as their primary disease had among the highest fraction of grafts lost to rejection (45.4% of all grafts lost) and the highest pretransplant sensitization rate (59.6%). 6. Recipients with HTN as their primary disease had overall lower 5-year graft survival (58% versus 63% in Whites, 44% versus 47% in Blacks), a lower rate of early allograft function (10% versus 12%, p < 0.00001), and more posttransplant dialysis needs (28.8% of patients requiring dialysis vs 23.5%, p < 0.00001) than recipients without HTN. Blacks with HTN had the lowest long-term graft survival (44.4%) of any other single group. 7. IDDM patients who expressed DR3 and/or DR4 alleles had significantly higher graft survival than patients without these DR groups. Whites expressing DR3 and DR4 and DR3 or DR4 alleles had better overall HLA matching (p < 0.001) and graft survival (75.4% and 70.7% versus 58.5% and 65.1%, p < 0.00001) than Blacks with similar DR expression. 8. SPK recipients had better 5-year graft survival than KAT recipients (66.2% versus 54.6%, p < 0.000001). This effect is most likely due to the selection of "better" lower-risk patients for SPK grafts.

Adolescent↗
PubMed1984

Efficacy of the condom as a barrier to the transmission of cytomegalovirus.

An in vitro model was used to determine whether latex condoms prevent the transmission of cytomegalovirus. When the condoms were submitted to stretching and trauma that simulated sexual intercourse, no transmission of cytomegalovirus across the condom barrier was detected. Condoms may therefore be used to minimize the transmission of cytomegalovirus via semen in both heterosexual and homosexual intercourse.

Coitus↗
PubMed1981

[Meconium ileus].

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Child, Preschool↗