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Biomedical subjects

C R Stiller

Publications and source records attributed to C R Stiller.

At least 55 records · Page 3Linked to original sources
PubMed1987

A randomized study of cyclosporine with and without prednisone in renal allograft recipients. Canadian Transplant Group.

Sixty-nine patients receiving Cs after cadaveric or LRD renal transplants were randomly allocated to receive prednisone or no prednisone beginning on the day of transplant. There were 36 in the prednisone group and 33 in the group assigned to no prednisone. Of these latter, only seven (21%) never received prednisone and an additional four had one short course for rejection episodes (11%). Of the remaining 22 who were placed on continuous steroids, only 12 met rejection criteria and either some or all of the remainder probably had Cs nephrotoxicity. The patient and graft survival were better but not statistically so in the no-prednisone group (97% v 89%) and (88% v 78%), and the number of infections was only half that of the prednisone-treated group (22% v 42%). A policy of withholding steroids except for rejection episodes does not prejudice graft or patient survival in Cs-treated patients.

Cyclosporins↗
PubMed1987

Cyclosporin-erythromycin interaction in normal subjects.

We studied the pharmacokinetic interaction between cyclosporin (CYA) and erythromycin in normal subjects. Plasma CYA concentrations were measured by high performance liquid chromatography (h.p.l.c.) and radioimmunoassay (RIA) and estimates of metabolite formation were obtained from inter-assay differences between these measurements. Erythromycin significantly increased the maximum concentration and the area under concentration-time curve. Time to maximum concentration and apparent oral clearance of CYA were significantly decreased. The half-life, however, was not altered. Significant reductions in the proportion of apparent metabolite were observed at times of maximum CYA concentrations but not at later time periods (12 and 24 h). The mechanism of the drug interaction appears to be decreased hepatic first-pass metabolism but an effect on CYA absorption cannot be excluded. These results on normal subjects confirm that patients administered CYA and erythromycin risk CYA toxicity. However, the risk can be reduced by dose reduction based on more frequent CYA monitoring or by using a different antibiotic.

Adult↗
PubMed1986

Nuclear magnetic resonance assessment of renal perfusion and preservation for transplantation.

The feasibility of using proton nuclear magnetic resonance (NMR) relaxation measurement to monitor organ perfusion and preservation was studied using a rat model. Intact kidneys were assessed with NMR following various periods of cold storage. Bilateral en bloc donor nephrectomy was performed on Sprague-Dawley rats with prior in situ flushing with Euro-collins', dextrose and other test solutions via a plastic cannula in the aorta. A paramagnetic agent, gadolinium-DPTA, dissolved in perfusion fluid was then injected into the renal vasculature. NMR analysis was repeated and the kidneys were reflushed with perfusion fluid to remove the gadolinium, followed by another NMR analysis. By sequential flushing and NMR measurement after 24, 48 and 72 hours of cold storage, the thoroughness of flushing, the patency of intrarenal vasculature and capillary integrity could be assessed. With the D5W, the T1 relaxation of kidneys dropped 56% with prolonged cold storage, indicating gadolinium accumulation in the interstitium, in effect loss of capillary integrity. With the Euro-collins', the T1 showed a small drop (23%) and almost complete flush-out, indicating superior tissue preservation and patency of vasculature. The addition of trifluoperazine, (TFP, a calmodulin inhibitor) to the Euro-collins' resulted in only a 9% drop in T1 after 72 hours. This possibly indicates TFP has additional protective action on cold ischemic damage. Using the small animal model presented here, proton NMR spectroscopy appears to be a sensitive technique in assessing renal vascular patency after cold storage and provides a useful tool for the investigation of other agents for organ preservation for transplantation.

Animals↗
PubMed1986

Kidney transplantation.

The current status of bone marrow transplantation is reviewed. The diseases that are treatable with marrow transplantation, the basic transplant procedure, and the potential complications of marrow transplantation are discussed in detail. The future application of marrow transplantation to additional disease processes is considered.

ABO Blood-Group System↗
PubMed1986

Removal of aluminum during hemodialysis: effect of different dialyzer membranes.

Aluminum toxicity is now widely recognized as a major cause of morbidity in patients on maintenance hemodialysis. Desferrioxamine (DFO) chelation therapy has been suggested as a method of AI removal in such patients, though the most appropriate treatment schedule is yet to be established. In the present study, AI removal following DFO infusion was evaluated using two different dialyzer membranes to test the hypothesis that polyacrilonitrile (PAN) membranes permit better AI clearance. All patients studied had significantly elevated plasma AI concentrations (1.22 to 9.45 mumol/L; normal less than 0.56 mumol/L). Plasma AI did not correlate with estimated total AI intake. During hemodialysis with a cuprophane membrane, AI clearance ranged from 33.5 to 42.1 mL/min. Total AI removal was 192.2 +/- 90.4 mumol during cuprophane dialysis. During hemodialysis with a PAN membrane, AI clearance ranged from 35.7 to 54 mL/min. Total AI removal was 154.2 to 93.9 mumol during PAN dialysis. The differences in AI clearance and total AI removal were not statistically significant. It is concluded that use of a PAN membrane does not significantly enhance DFO-AI clearance.

Acrylic Resins↗
PubMed1986

Clinical leukocyte phenotyping by laser flow cytometry and monoclonal antibodies (immunocytometry) in renal transplantation.

Absolute levels of peripheral blood mononuclear cells were sequentially monitored by immunocytometry in 54 consecutive renal allograft recipients receiving azathioprine/prednisone (STD gp, N = 16) or cyclosporine with or without prednisone (CsA gp, N = 38), before and after transplantation. In the CsA group, but not in those receiving STD therapy, the mean absolute levels of all but OKT4+ cells increased significantly with the duration of therapy. In both treatment groups (STD + CsA), the mean % delta OKT4/8 ratio increased from a prerejection quiescent value of 80 +/- 6% SE to a rejection value of 120 +/- 6% (P less than .001) and fell back to 77 +/- 6% (P less than .0005) in postrejection quiescence. The sensitivity and specificity of such an elevated ratio for rejection were 84.4% and 88.6%, while positive and negative likelihood ratios were 7.40 and 0.15, respectively. In rejection, concomitant immunopathology showed a predominance of OKT8+ cells in the graft with a mean T cell subset ratio of 0.8 +/- 0.3 SE in renal biopsies compared to 2.0 +/- 0.3 for circulating cells (P less than .0125). Parallel donor-antigen-specific assay of lymphocyte-mediated cytotoxicity (LMC) became positive with graft rejection. Immunocytometry with normalization of sequential data in longitudinal analysis thus appears to be a valuable tool in immunologic laboratory monitoring of graft rejection.

Adolescent↗
PubMed1986

Microvascular surgery as an adjunctive tool in renal transplantation.

There has been a serious shortage of suitable kidneys for transplantation since this procedure became the treatment of choice for many patients with end-stage renal failure. Some harvested kidneys are discarded due to complicated or injured renal vasculature and some potential living related donors are judged unsuitable because their kidneys have multiple vessels. The authors review the basic microsurgical techniques they have used in such situations to salvage kidneys for transplantation. They emphasize the ex-vivo, "bench", microsurgical method for protecting the kidney from prolonged warm ischemia time (as with multiple complicated in-situ anastomoses). Several illustrative case reports from their recent experience are presented. The authors conclude that microvascular surgery is an important adjunct to the armamentarium of the transplant surgeon.

Adult↗
PubMed1985

Disappearance and reappearance of islet cell cytoplasmic antibodies in cyclosporin-treated insulin-dependent diabetics.

In 68 newly diagnosed patients with insulin-dependent diabetes mellitus (IDDM) whose treatment included cyclosporin (CyA) the prevalence and mean titre of islet cell cytoplasmic antibodies (ICA) fell faster than they did in the 56 who received only insulin. However, in the CyA-treated patients the prevalence or titre of ICA at diagnosis did not correlate with beta-cell function as measured by glucagon-stimulated C-peptide levels; improvement and recovery of beta-cell function after 30 days of CyA therapy occurred despite the continued presence of ICA; and CyA-induced remission of IDDM (ie, glucagon stimulated plasma C-peptide levels greater than 0.6 pmol/ml) was not predicted by nor coincident with disappearance of ICA. Therefore, although CyA therapy was associated with a higher than expected frequency of remission and faster disappearance of ICA, the two observations were not temporally and may not be causally related. ICA should not be used to identify the target population for or to predict response to immunosuppressive therapy. The contribution of ICA to the pathogenesis of beta-cell destruction in IDDM needs serious re-examination.

Adolescent↗
PubMed1985

Inhibition of human in vivo cytotoxic T lymphocyte generation by cyclosporine following organ transplantation.

The effect of cyclosporine (CsA) on the in vivo cell-mediated immune response to donor antigens was examined sequentially following cadaveric renal transplantation in both immunologically naive and specifically sensitized allograft recipients. Cytotoxic T lymphocytes (CTL) exhibiting preferential specificity for donor antigens were detected in the peripheral blood of all patients receiving azathioprine (AZA) immunosuppression by two weeks posttransplant, disappearing progressively over the first three months with clinical quiescence. In contrast, the generation of donor-reactive CTL was significantly diminished in incidence (P = 0.05) and in magnitude (P = 0.004) in subjects receiving CsA. CTL were detected in only 36% of patients by two weeks posttransplant, and were not detectable in any CsA-treated patient after the sixth posttransplant week. The ability of CsA to inhibit clonal reexpansion of CTL was examined both in vitro and in vivo in subjects exhibiting prior sensitization to donor antigens. In vitro, CsA caused a dose-dependent inhibition of accelerated (72-hr MLC) CTL generation following restimulation with donor spleen cells, which was quantitatively identical to that in parallel cultures using responder PBL from non-sensitized individuals. In vivo, CsA produced a rapid disappearance of circulating CTL posttransplant in patients who exhibited specific cell-mediated sensitization to the graft donor, as evidenced by the presence of circulating donor-reactive CTL prior to transplantation. In contrast, in patients receiving AZA there was a rapid increase in donor-reactive CTL in the peripheral blood following transplantation. CTL persisted for six weeks or longer, and two of four patients lost the graft to irreversible acute rejection within the first four weeks.

Azathioprine↗
PubMed1985

Liver transplantation: the initial experience of a Canadian centre.

At the University Hospital in London, Ont., 19 patients have received 24 liver transplants. The commonest indications for transplantation were primary biliary cirrhosis and cirrhosis from chronic active hepatitis. The first three patients in the series died of infectious complications. Eleven of the subsequent 16 recipients are alive from 5 months to 2 1/2 years after transplantation. Eight patients who are alive more than 1 year after the operation have an excellent quality of life. Cyclosporine and steroids in combination are used for immunosuppression. With current surgical techniques, modern immunosuppression and good patient selection, the restoration of patients with advanced irreversible liver disease to good health by liver transplantation is a realistic goal. Much effort and considerable resources are required to run a liver transplant program.

Adolescent↗