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Biomedical subjects

R H Kerman

Publications and source records attributed to R H Kerman.

At least 91 records · Page 5Linked to original sources
PubMed1987

Factors determining renal transplant outcome at the University of Texas at Houston.

CsA-Pred therapy yields equivalently good patient survival for LRD and 2 degrees CAD versus 1 degree CAD transplants. There is a long-term graft survival advantage for LRD versus 1 degree CAD transplants (5 years; 83% vs 58%). 2 degrees CAD transplants have inferior graft survival when compared with 1 degree CAD grafts (one year; 78% vs 67%). Multiple donor factors adversely affecting graft outcome include increased warm and cold ischemia times, pulsatile perfusion, use of pressors or diuretics in the donor, donor age less than 10 years, donor blood transfusions, and kidneys shipped from other centers. Recipient factors adversely affecting graft outcome include retransplantation and CMV infection as well as noncompliance with therapy. HLA-matching and pretransplant blood transfusions have not contributed in a statistically significant way to graft outcome although they may affect the quality of graft function at this center. Immunosuppressive therapy with CsA-Pred must be tailored to the individual patient. Continuous IV CsA infusion in the preoperative period and slow steroid taper impact favorably on graft outcome. The complications of CsA therapy include neuroectodermal toxicity, hepatotoxicity, and most importantly, nephrotoxicity. Other problems unique to CsA-Pred therapy include hypertension, delayed graft thrombosis, and de novo hemolytic uremic syndrome. Hepatotoxicity may eventuate in biliary and pancreatic complications necessitating surgical therapy. The overall incidence of infection and neoplasm remains low with CsA-Pred therapy. The use of therapeutic trough CsA level monitoring, as well as pharmacokinetic and pharmacodynamic analyses may assist in clinical decision making regarding administered doses, dosing interval, and discrimination between rejection and nephrotoxicity.

Adolescent↗
PubMed1986

Amyotrophic lateral sclerosis. Associated clinical disorders and immunological evaluations.

We examined the family history and associated diseases in 58 patients with amyotrophic lateral sclerosis (ALS), as well as the T-cell phenotypes and functions in 46 consecutive patients with this disorder. A family history of thyroid disease was present in 19%, and an additional 21% of patients described family members with other possible autoimmune disorders. In 19% of the patients with ALS either past or present thyroid disease was documented. Eleven of 47 additional patients with ALS had significant elevations of microsomal and/or thyroglobulin antibody levels. The T-cell phenotypes and functions were comparable in the ALS and control groups, with the exception of the presence of Ia antigen. In patients with ALS, 11.9% of the T cells were positive for the la antigen, while in both a normal control population and a non-ALS neurologic disease population, only 6.4% of T cells have this antigenic determinant. These data support involvement of autoimmune mechanisms in ALS.

Adult↗
PubMed1985

Does cyclosporine influence the results of cadaver retransplantation?

The results of cadaveric retransplantation in 55 recipients immunosuppressed with cyclosporine and prednisone were compared to 156 recipients of primary renal allografts. By 3 yr posttransplant, there is no significant difference in patient survival, but the yearly graft survival for primary (79%, 72%, 72%) as compared to retransplant (69%, 58%, 58%) recipients was significantly (p less than 0.05) better. There was no significant difference in rejection episodes or mean +/- SD serum creatinine (mg/dl) at 2 yr between primary (32%, 2.14 +/- 1.1) and retransplant (33%, 2.08 +/- 1.4) patients, respectively. Donor source, third kidneys, human leukocyte antigen AB and Dr matching, percent reactive antibody levels, and cause of first graft loss do not have significant impact on cyclosporine-treated retransplant outcome. However, retransplant patients who have lost a previous graft in less than 3 months continue to be at high risk for subsequent early graft loss. These results suggest that the combination of cyclosporine and prednisone is the preferred regimen for cadaveric retransplantation.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1985

Impact of cyclosporine on renal transplant practice at the University of Texas Medical School at Houston.

CsA has improved the outcome of renal allotransplantation with CAD and LRD kidneys. CsA mitigates risk factors heretofore presenting substantial obstacles to CAD transplantation: HLA matching, pretransplant splenectomy, extensive numbers of conditioning blood transfusions, and old age. In LRD transplantation, CsA obviates the need for donor-specific transfusions in the haploidentical situation, and for prednisone in the HLA-identical setting. The incidence of drug-induced nephrotoxicity beyond six months is 30% with the degree of dysfunction proportionate to the degree of histo-incompatibility, suggesting that subclinical allograft rejection due to overzealous dose reduction may compromise allograft function. At present, total conversion from CsA to Aza appears ill-advised; even patients who never suffered allograft rejection under CsA therapy frequently lose their allograft when the inferior level of Aza suppression is substituted. Drug-induced hypertension, a modestly significant factor, diminishes further by two years posttransplant. The benefit of CsA therapy is a reduced incidence of 19% initial and 10% recurrent rejection episodes. Of great importance is the observation that 17% of rejection episodes followed patient noncompliance. Further, the incidence of bacterial infections was greatly reduced, and viral infections modestly lessened. Only the occurrence of pneumocystis carinii was increased, but 92% of patients survived in spite of serious pulmonary infection. Development of a consistent CsA regimen has reduced the median initial hospitalization to 12.5 days for LRD and 14 days for CAD, a level well within the range stipulated for the Disease-Related Guidelines of the Medicare Program. Furthermore, readmission is less frequent; one-third of patients never reenter the hospital.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1985

Successful transplantation of cyclosporine-treated allograft recipients with serologically positive historical, but negative preoperative, donor crossmatches.

Eighteen renal allograft recipients (15 cadaveric and 3 haploidentical living-related donor transplants) with historically (Hx)3 positive, but pretransplant (pre-Tx) negative, donor crossmatches (XM) were treated postoperatively with cyclosporine (CsA) and prednisone (Pred). The one-year allograft survival for the 14 primary allograft recipients was 86% (12/14). This was comparable to, and not significantly different from, the 81% (51/63) graft survival for recipients of primary cadaveric donor allografts transplanted during the same period who displayed a negative donor crossmatch with both Hx and pre-Tx sera. All four retransplant recipients with (+) Hx, but (-) pre-Tx, donor Xms lost their grafts. This result was significantly different (P less than 0.05) from the 75% (27/36) graft survival for retransplant recipients displaying a negative donor crossmatch with both Hx and pre-Tx sera. A significant decrease in PRA of 52 +/- 19% to 19 +/- 16%, P less than 0.05, was displayed by 12/18 CsA patients when comparing (+) Hx to (-) pre-Tx sera, which could have influenced the allograft survival in those patients. However, a graft survival of 44% (4/9) was observed for azathioprine (Aza) and Pred-treated recipients of cadaveric donor renal allografts who also displayed a significant decrease in PRA of 50 +/- 22% to 5 +/- 4%, P less than 0.05 when comparing Hx to pre-Tx sera. The decreasing PRA did not beneficially affect these Aza-Pred patients' graft survival. Therefore, CsA-Pred afforded a beneficial effect when recipients of a primary cadaveric renal allograft displaying a (+) Hx, but (-) pre-Tx, XM were transplanted. Retransplant recipients, however, should receive a cadaveric donor allograft only when they are XM-unreactive, whether testing with pre-Tx or Hx sera.

ABO Blood-Group System↗
PubMed1984

Comparison of biopsy-proven Pneumocystis carinii pneumonia in acquired immune deficiency syndrome patients and renal allograft recipients.

Pneumonia unresponsive to antibacterial agents in patients with acquired immune deficiency syndrome (AIDS) has become a new indication for lung biopsy. In 14 patients, transbronchial or open-lung biopsy demonstrated Pneumocystis carinii. An additional 12 patients, who were immunosuppressed after renal transplantation, were seen with P. carinii pneumonia. The diagnosis was established by transbronchial biopsy in the majority of patients. All patients were treated initially with trimethoprim plus sulfamethoxazole. Pentamidine was added after diagnosis if improvement did not occur. Both groups demonstrated reversal in the T cell helper: suppressor ratio. We compared these two groups of immunocompromised patients with respect to clinical presentation, lung pathology, response to therapy, and survival. Patients with AIDS were seen with a two- to three-week prodrome of fever, lymphadenopathy, weight loss, and malaise followed by hypoxia and leukopenia within 12 hours. Transplant patients became acutely ill with fever and hypoxia within 24 to 36 hours. In both groups, chest roentgenogram showed bilateral diffuse infiltrates; sputum cultures were generally negative; and lung biopsy demonstrated Gomori-Jones periodic acid-methenamine-silver-positive P. carinii. Mortality was substantially higher in patients with AIDS (50% versus 8%). This difference may be explained by the fact that the T cell defect in AIDS has an infectious cause, while the defect in the renal allograft recipient is pharmacologically mediated.

Acquired Immunodeficiency Syndrome↗
PubMed1984

Successful transplantation of cyclosporine-treated haploidentical living-related renal recipients without blood transfusions.

A protocol of cyclosporine and prednisone immunosuppression was used in 36 consecutive haploidentical living-related renal transplant recipients from donors displaying marked proliferation in mixed lymphocyte culture (MLC) reactions. All blood transfusions (random third-party and donor-specific) were withheld once a negative crossmatch with the prospective kidney donor was obtained. With a mean follow-up of 13.6 months, patient survival is 97% (35/36) and graft survival is 92% (33/36). One graft was lost to rejection; two were abandoned because of sepsis. Only 14% (5/36) of patients experienced a rejection episode. No significant differences were evident in graft survival, rejection episodes, or renal function between the 15 recipients who were never transfused and the 21 with a history of previous blood transfusions. These findings suggest that pretransplant blood transfusions not only are unnecessary to achieve excellent graft survival, but also may jeopardize donor availability by donor-specific presensitization.

Adolescent↗
PubMed1984

Immunopharmacodynamic evaluation of cyclosporine-treated renal allograft recipients.

Since the mode of action of cyclosporine (CsA) in man is incompletely understood, there are no monitoring tools to assess immunosuppressive effect in vivo. In vitro CsA inhibits lymphoproliferation in response to allogeneic and mitogenic stimuli, presumably due to reversible suppression of T helper cell generation of interleukin-2. Therefore the present studies examined the immunosuppressive effect of patient sera on a third-party mixed lymphocyte reaction (MLR) as a pharmacodynamic approach to quantify patient responses to CsA administration. Four kinetic patterns of in vitro immunosuppressive activity were discerned: 24/28 (86%) patients showing two cycles of MLR inhibition--namely, a first peak corresponding to absorption of CsA and an independent second peak of immunosuppression (type I), were free of rejection; while 17/23 (74%) patients demonstrating one cycle corresponding to the peak of CsA absorption (type II) suffered rejection episodes (P less than 0.001). In addition, 20 patients generating continuously high levels of in vitro serum activity (type III) were almost all free of rejection, but manifested nephrotoxicity; while two patients showing continuously low levels (type IV) suffered graft loss due to irreversible rejection (P less than 0.01). Thus failure to display either a second peak or continuously high levels of MLR inhibition was associated with a markedly increased incidence of rejection (76% versus 16%). The in vitro functional characteristics of peak-2 were similar to those of CsA, as assessed by the kinetics of inhibition of MLR lymphoproliferation or cell-mediated lympholysis (CML), and by gross chemical properties of partitioning into organic solvents and heat stability. These findings suggest that pharmacodynamic analysis by MLR inhibition not only affords a useful parameter of immunosuppression, but also may provide an in vitro model to dissect the generation and biotransformation of active CsA metabolites.

Cyclosporins↗
PubMed1984

The use of cyclosporine in living-related renal transplantation. Donor-specific hyporesponsiveness and steroid withdrawal.

Fourteen HLA-identical (HLA-ID) and 62 haploidentical (HP-ID) living-related donor (LRD) renal allograft recipients were transplanted using cyclosporine (CsA) and prednisone immunosuppression. No patients were preconditioned with pretransplant blood transfusions (third-party or donor-specific)--and, therefore, none were sensitized to their donor. Patient 93% (13/14) and graft 93% (13/14) survival for the HLA-ID patients is not significantly different (P greater than .1) compared with patient 98% (61/62) and graft 91% (56/62) survival in the HP-ID patients, with a mean follow-up of 16.3 (8-30) and 14.7 (2-35) months, respectively. A significant difference was noted in the incidence of treated rejection episodes (0% vs. 31%, P less than .01) and the mean serum (mg/dl) creatinine (1.37 vs. 1.71, P less than .05) at 18 months between the HLA-ID and the HP-ID and HP-ID recipients, respectively. Ten of 22 HP-ID recipients demonstrated donor-specific mixed lymphocyte culture hyporesponsiveness one year posttransplant that may have been due to the emergence of monocytoid suppressor cells. Nine of these HP-ID and seven HLA-ID recipients were subjected to a protocol of steroid withdrawal. Eleven of these patients are currently on CsA monodrug therapy and two are on alternate-day steroids from 9-18 months after discontinuation of prednisone. These findings suggest that CsA is an effective steroid-sparing agent in LRD renal transplantation that diminishes the frequency of treated rejection episodes and may permit monodrug therapy in selected individuals.

Adult↗