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Biomedical subjects

R H Kerman

Publications and source records attributed to R H Kerman.

At least 55 records · Page 3Linked to original sources
PubMed1991

The role of crossmatching in organ transplantation.

The preoperative crossmatch is one of the most important laboratory tests in organ transplantation. Quality assurance of this laboratory test depends on a number of factors that include the serum samples and methodology utilized. Clinical correlation with laboratory studies and postoperative outcome of the graft and the recipient are essential to understanding this developing field.

Flow Cytometry↗
PubMed1990

Proteinuria in cyclosporine-treated renal transplant recipients.

Of 704 renal transplant recipients receiving long-term cyclosporine immunosuppression, 71 patients experienced proteinuria greater than 1 g/24 hr beyond the first month posttransplant. Eight patients displayed transient proteinuria, defined as lasting less than 3 months. In most cases this condition was attributed to biopsy-proved acute rejection. The transient proteinuria cohort experienced good graft outcome--namely, 87.5% one-year and 52.5% five-year actuarial graft survivals, which was similar to that observed in patients without proteinuria. In contrast, 52.4% of the 63 patients with nontransient proteinuria experienced graft loss within a median time of 6.1 months. The one- and five-year actuarial graft survivals in patients with nontransient proteinuria were 75.3% and 37.5%, respectively. Among the 63 patients with nontransient proteinuria, histopathologic diagnosis included chronic rejection in 19, transplant glomerulopathy in 14, acute rejection in 9, glomerulonephritis (GN) in 7 including 2 cases of membranous GN, and nonspecific interstitial fibrosis in 10 cases. Despite the overall poor prognosis for graft survival among the entire cohort of patients with nontransient proteinuria, the seven with allograft GN maintained prolonged graft function. They showed an 83.3% five-year actuarial graft survival versus 31.2% in patients with other causes of proteinuria (P = 0.043). These results suggest that posttransplant proteinuria in CsA-treated renal transplant recipients arises primarily as a consequence of allograft rejection and portends a poor graft outcome.

Cyclosporins↗
PubMed1990

Improved graft survival for flow cytometry and antihuman globulin crossmatch-negative retransplant recipients.

We compared our standard NIH (extended incubation) crossmatch (XM) with antihuman globulin (AHG) and flow cytometry XMs and correlated the results with rejection episodes and graft survivals. For 89 CsA-Pred, primary renal allograft recipients, AHG and/or FCXM results did not improve on the NIH-XM-negative (NEG) graft survival results, whether testing pretransplant or historical (Hx) sera. Similarly, there was no association of a positive (POS) AHG or FCXM with increased rejection episodes in these primary recipients. However, for retransplant (Re-Tx) recipients a neg AHG or FCXM did discriminate fewer rejections and an improved graft survival compared with the NIH-XM-neg. results. The overall one-year graft survival for the 47 Re-Tx recipients studied herein was 66% (based on a neg pre-Tx NIH-XM). Pre-Tx AHG-NEG, Re-Tx recipients displayed an improved graft survival compared with NIH-XM NEG recipients (77% vs. 66%, P less than 0.05) and with AHG-POS recipients (77% vs. 47%, P less than 0.05). Similarly, pre-Tx, FCXM-NEG, Re-Tx recipients displayed improved graft survivals compared with NIH-XM-NEG recipients (83% vs. 66%, P less than 0.05) and FCXM-POS recipients (83% vs. 48%, P less than 0.05). Re-Tx recipients displaying a POS AHG and/or FCXM experienced a significantly greater number of rejections than NEG-XM recipients (P less than 0.05, respectively). The AHG and FCXM results correlated with rejections and graft survivals whether testing pre-Tx or Hx high-PRA sera. Re-Tx recipients who were AHG-XM-NEG but FCXM-POS, experienced more rejection episodes than recipients who displayed a negative XM reactivity for both AHG and FCXM (P less than 0.02), but with no resulting differences in graft survival. HLA matching, pre-Tx blood transfusions and PRA did not impact on these crossmatch and graft survival results. Use of AHG and/or FCXMs for Re-Tx, but not primary, recipients should help to improve graft survival for these high-risk recipients.

Antibodies, Anti-Idiotypic↗
PubMed1990

Sensitivity of intracellular signals responsible for cell cycle progression to cyclosporine.

Within the cascade of intracellular activation signals triggering T lymphocyte effector response to alloantigen is a cytoplasmic protein, ADR, that activates DNA replication in isolated nuclei. Quantitative changes in ADR (exclusive to activated cells) regulate cell cycle progression and may indicate changes in intracellular proliferative control. The present communication documents that inhibition of ADR activity reflects the in vitro immunosuppressive effects of Cyclosporine. CsA inhibition of both proliferation and generation of ADR was concentration-dependent and occurred only in the G0 phase of the cell cycle. Drug addition did not affect G1 cells. ADR generation was inhibited both by CsA and by PGE2 alpha, possibly via effects on calcium-dependent activation pathways confined to G0/G1 transition. On the other hand, ADR generation was not inhibited by the immunosuppressive agents 6-mercaptopurine, Enisoprost (a PGE1 analog), or FK506. ADR activity was sensitive to aprotinin, which typically inhibits serine proteases. Using an enzymatic assay to quantitate serine protease activity (SPA) following PHA stimulation revealed that ADR content inversely correlated with SPA: ADR was only present in activated cells; SPA was highest in resting cells and decreased after PHA stimulation. The PHA-induced fall in SPA activity was inhibited by CsA, consistent with the failure to generate ADR. Like ADR, SPA was sensitive to PGE2 alpha and quantitatively unaffected by 6-mercaptopurine, Enisoprost, or FK506. Thus, ADR and SPA may represent opposing components of a cytoplasmic signaling cascade the balance of which reflects the level of immunosuppression, and thus represents a focus for in vitro evaluation of the immunologic response of allografted patients to cyclosporine.

Aprotinin↗
PubMed1990

Immune studies in human immunodeficiency virus infection with myasthenia gravis: a case report.

A patient with human immunodeficiency virus infection had cellular and humoral immune responses studied longitudinally from the onset of generalized myasthenia gravis. Progressive decline in CD4+, CD45R+ and CD4+, CDw29+ T-cells, cellular immune responses to alloantigen and mitogen stimulation, and acetylcholine receptor antibody titers were associated with clinical improvement of all myasthenic symptoms.

Adult↗
PubMed1989

Effect of cyclosporine on rubella virus-specific immune responses in chronic progressive multiple sclerosis.

Cyclosporine A (CsA) has been used in putative autoimmune diseases after sensitization to unknown antigens. We have previously shown that CsA prevented continued activation of T-cells in chronic progressive multiple sclerosis (CPMS) patients. The current study was undertaken to determine whether CsA, or CsA and prednisone (CsA + P) could suppress immune responses to a common recall antigen. Serum antibody levels were higher in all CPMS patients than age-matched normal controls. However, rubella antibody titers in the CsA or CsA + P groups were no different from a placebo-treated CPMS patient group. The lymphocyte responses to inactivated rubella virus of CsA and CsA + P-treated CPMS patients were lower than placebo and control but not statistically different. Therapy with both CSA and CSA + P was associated with significantly lower panel mixed leukocyte responses and Ta1 expression than in the placebo-treated group; CD3, CD4, CD8 antigen expression and active rosette formation by T-cells were similar for the three CPMS groups. These results suggest that while CsA exerts measurable effects on non-specific indicators of cellular immunity in CPMS patients, it may not be as effective in suppressing pre-existent specific immune responses.

Antibodies, Viral↗
PubMed1989

Stability of renal allograft function associated with long-term cyclosporine immunosuppressive therapy--five year follow-up.

To examine the evolution of renal allograft function in kidney transplant recipients receiving long-term cyclosporine therapy, we evaluated 50 cadaveric and 30 living-related renal transplant recipients having graft survival greater than or equal to 12 months and an opportunity for 5 years of follow-up. Linear analysis of long-term allograft function in each patient was undertaken by plotting reciprocal serum creatinine (1/Crs) values vs. time. Mean follow-up was 49 +/- 18 months. Actual 3-year and 5-year allograft survivals were 83.8% (n = 80) [corrected] and 73.3% (n = 75) [corrected], respectively. Collective analyses of values of 1/Crs measured at yearly intervals and of the slopes of the curves obtained by plotting 1/Crs vs. time for each patient suggested that long-term use of CsA is associated with impaired but generally stable allograft function 1-5 years posttransplant. The aggregate rate of decline of renal allograft function in the study population did not differ from that of a historical control group consisting of 59 renal transplant recipients treated with a conventional prednisone-azathioprine immunosuppressive regimen. Donor source, diabetes, and diastolic hypertension (diastolic BP greater than 95 mmHg in more than half the follow-up readings) were not correlated with a more rapid rate of decline of allograft function as reflected in the slopes of the 1/Crs vs. time curves between 12 months posttransplant and the end of follow-up. In contrast, a significantly greater rate of decline of cadaveric allograft function was observed in patients with 12-month Crs values greater than 2.5 mg% and recipients of greater than 2 HLA-A,B-mismatched cadaveric kidneys. The data do not support an indication for routine conversion from CsA to azathioprine following successful renal transplantation.

Adolescent↗
PubMed1988

Serial immune evaluation of cyclosporine- and placebo-treated multiple sclerosis patients.

During an ongoing clinical trial of cyclosporine (CsA) immunosuppression therapy for chronic progressive multiple sclerosis (MS), a comparison was made of the immune responses of 18 CsA- and 18 placebo (P)-treated MS patients. Patients randomized to receive either CsA or P had identical entry immune profiles. However, these MS patients displayed significantly increased T-helper:T-suppressor (TH:TS) ratios (P less than 0.01), percentage (%) active-T (P less than 0.01), % Ia+-T (P less than 0.05) and % Ta1+-T (P less than 0.01) cell phenotypes when compared to age-matched normal controls. Further, the MS-P-treated patients displayed significant increases (all P less than 0.01) in % pan-T, % helper-T, % active-T and % Ta1+-T cell phenotypes as well as panel mixed lymphocyte culture (panel MLC) functional responsiveness from entry to cumulative 12-month study data. In contrast, the MS-CsA-treated patients only displayed an increased % pan-T cell phenotype. The cumulative 12-month follow-up data showed that the MS-P-treated patients displayed significantly higher immune parameters than the MS-CsA-treated patients for % pan-T (P less than 0.05), % helper-T (P less than 0.01), TH:TS ratio (P less than 0.05), % active-T (P less than 0.01), % Ta1+-T cells (P less than 0.01) and panel MLC stimulation index (P less than 0.01). Thus, MS-CsA-treated patients did not display the progressive immune activation seen on serial evaluation during the follow-up time period that characterized the placebo-treated MS group.

Acute Disease↗
PubMed1988

The impact of cytomegalovirus infection on seronegative recipients of seropositive donor kidneys versus seropositive recipients treated with cyclosporine-prednisone immunosuppression.

To assess the impact of cytomegalovirus (CMV) infection in D+R- patients treated with cyclosporine (CsA)-prednisone immunosuppression, we compared the incidence of CMV infection, severity of disease, and the 1, 2, and 3-year actual graft and patient survival rates of CMV-infected D+R- patients with R+ patients from a group of 516 renal allograft recipients at our center. CMV infection occurred more frequently in 27/56 D+R- patients (48%) versus 111/376 R+ patients (29%) (P less than 0.01). The incidence of CMV was also significantly greater in D+R- versus R- patients receiving CAD grafts (59% vs. 32%, P less than 0.01) and first transplants (47% vs. 30%, P less than 0.05). There were no significant differences in CMV disease severity between the aggregate D+R- and R+ patient groups and when subgroups of these patients receiving cadaveric donor (CAD), living-related donor (LRD), first, or retransplant allografts were compared. The actual 1, 2, and 3-year graft survival rates for D+R- patients (68%, 58%, 68%) were not significantly different from rates in R+ patients (83%, 77%, 63%) with CMV infection. When the 1, 2, and 3-year actual graft survival rates in subgroups of D+R- and R+ patients were compared in CAD, LRD, and first and retransplants, there were no significant differences. The actual 1, 2, and 3-year patient survival rates were not significantly different between D+R- (89%, 92%, 100%) and R+ patients (94%, 91%, 86%) with CMV infection, nor were they different when CMV infected D+R- and R+ patients with CAD, LRD, first or retransplant grafts were compared. These data do not support the policy of denying a seropositive kidney to a seronegative recipient, since the severity of CMV disease and the impact of CMV infection is not significantly different comparing D+R- and R+ patients receiving CsA-prednisone immunosuppression.

Adolescent↗