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Biomedical subjects

C R Stiller

Publications and source records attributed to C R Stiller.

At least 19 recordsLinked to original sources
PubMed1991

Endocrine-metabolic function in remission-phase IDDM during administration of cyclosporine.

We have studied the endocrine-metabolic status of patients in non-insulin-receiving (NIR) remission of insulin-dependent diabetes mellitus (IDDM) within 6-60 mo of diagnosis during administration of cyclosporine, in comparison with nondiabetic subjects. IDDM patients in NIR remission were recognized when target glycemic control (plasma glucose and mean capillary blood glucose levels less than 7.8 mM before meals) was maintained without administration of insulin for at least 2 wk. In so-called isoglycemic tests, 50 g glucose was administered orally, and the glycemic curve was simulated in a subsequent study by programmed intravenous infusion of glucose. Under these conditions, the subjects with diabetes exhibited obvious glucose intolerance: acute beta-cell responses to intravenous glucose were virtually absent but significant, although subnormal responses were present after oral glucose. The responses of plasma immunoreactive gastric inhibitory polypeptide to oral glucose were normal. After bolus intravenous injections of glucose, the patients with diabetes again exhibited glucose intolerance; acute responses of immunoreactive insulin (IRI) and C-peptide were present, although grossly obtunded. On intravenous infusion of arginine (30 g in 30 min), the patients with diabetes showed substantial but subnormal increases in plasma IRI and C-peptide. Intravenous infusion of arginine elicited increments of plasma immunoreactive glucagon (IRGI) in both groups, and this response was slightly exaggerated in the patients with diabetes. On ingestion of a standard mixed meal (Sustacal) delivering 600 cal, there was a modest but significantly greater increase in plasma glucose levels in the diabetic subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

Interaction of bromocriptine and cyclosporine in insulin dependent diabetes mellitus: results from the Canadian open study.

Although cyclosporine A (Cy-A) is effective in modifying the initial course of newly diagnosed insulin dependent diabetes mellitus (IDDM) it has a number of side effects, particularly renal, which limit its use. In this study we investigated the potential synergistic effects of bromocriptine (BCR) therapy in treating patients with newly diagnosed IDDM. Three groups of patients were treated: (1) fourteen patients on Cy-A who required a decrease in their dose due to elevated creatinine; (2) four newly diagnosed patients whose initial therapy consisted of low dose (5 mg/kg/day) Cy-A and 10 mg/day of BCR; (3) eight patients whose glucagon-stimulated connecting-peptide (C-peptide) levels were greater than 0.3 nmol/l but whose insulin requirements were over 0.3 U/kg/day and whose Cy-A was to be discontinued. The results suggest that there was no statistically significant difference in stimulated C-peptide, glycosylated haemoglobin, daily insulin dose or serum creatinine. However, the trend suggested that BCR may have some protective effect on preserving endogenous insulin secretory capacity, although glycosylated haemoglobin and daily insulin dose increased. The results do not suggest that patients with newly diagnosed IDDM significantly benefit from concurrent BCR and Cy-A therapy.

Blood Glucose↗
PubMed1990

Induction and pathophysiology of remission of insulin-dependent diabetes mellitus during administration of ciclosporin. London Diabetes Study Group.

Ciclosporin-induced noninsulin-receiving remissions in insulin-dependent diabetes mellitus are associated with enhancement of beta-cell function. Patients in remission show virtually no insulin responses to parenteral glucose, contrasting with substantial responses to mixed meals, indicating effects of nonglucose nutrients and/or enteroinsular mechanisms. Remission is associated with normal insulin sensitivity; loss of insulin sensitivity can lead to relapse. The risks of the treatment call for studies with lower doses, and it is argued that a continuing search for immunomodulatory interventions that enhance and preserve the clinical remission-phase characteristics should be pursued.

Adolescent↗
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↗
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↗
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↗