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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
PubMed1993

Human mouse chimeric CD7 monoclonal antibody (SDZCHH380) for the prophylaxis of kidney transplant rejection.

mAb directed against CD7 have been shown to inhibit T cell proliferation in the allogeneic mixed lymphocyte reaction suggesting that CD7 may be an appropriate target for in vivo immunotherapy. We performed a prospective randomized clinical trial with a human-mouse chimeric CD7 mAb (SDZCHH380) and compared it with murine OKT3 for the prophylaxis of kidney transplant rejection. Twenty recipients of first cadaveric renal allografts were randomized to receive either SDZCHH380 or OKT3. SDZCHH380 was well tolerated. Rejection was delayed to day 35. No patients were sensitized to SDZCHH380. In contrast 7/10 OKT3 patients made anti-OKT3 antibodies. SDZCHH380 coated peripheral blood and lymph node T cells and, in contrast to OKT3, induced minimal release of IL-2, IL-6, TNF-alpha, and IFN-gamma. In addition, we showed that CD7-negative T cells mediated rejection in one of the SDZCHH380-treated patients. We conclude that the human-mouse chimeric CD7 mAb SDZCHH380 is well tolerated, is not immunogenic, and merits further study in the prophylaxis of transplant rejection.

Adolescent↗
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↗
PubMed1988

Liver transplantation: the University Hospital-Children's Hospital of Western Ontario experience.

Patients who currently benefit the most from liver transplantation are those with end-stage, non-malignant liver disease. Primary biliary cirrhosis and cirrhosis from chronic active hepatitis (hepatitis B negative) have been the most common indications in our experience. Overall survival rates in excess of 70% at 1 year are now common and those patients who live the first year have a very good prospect of long-term survival. Complete rehabilitation occurs in about 80% of survivors. Patients on life support systems before transplantation and those awaiting urgent retransplantation have the highest mortality rates. Modern anesthetic and surgical techniques have made the operation much safer and more straightforward. Biliary tract complications remain common, especially in patients with a history of previous upper abdominal surgery. Cyclosporine has had a major impact, but in the context of its use in combination with other immunosuppressive agents (antilymphocyte globulin, steroids, azathioprine and OKT3).

Actuarial Analysis↗
PubMed1988

Dialysis or transplant: an integrated approach to end-stage kidney disease management.

Technological and immunological developments within the last decade have evolved a variety of therapeutic modalities by which ESRD may be satisfactorily managed. With the exception of renal transplantation between identical twins, none of these modalities provide permanent and complete correction of the uremic state, however, and the challenge now facing those involved in the management of irreversible renal failure is to devise an individualized treatment program permitting optimal long-term physical and psychological well-being and the maintenance of a valuable and productive role in society. Such a goal is most effectively achieved by an integrated approach combining both dialysis and renal transplantation. In the program proposed and utilized at our institution, all therapeutic options are presented to the patient with incipient renal failure, and a rational long-term management strategy devised based on clinical status, psychological stability, convenience, and acceptability. Dialysis is normally employed as a limited term maintenance procedure pending renal transplantation from a living or cadaver donor, thus permitting optimal correction of the uremic state. Early rehabilitation and social reintegration are actively pursued to minimize disease impact and maximize quality of life. In subjects with chronic deterioration of graft function, retransplantation may be performed prior to requirement for dialysis, thus minimizing hospitalization time, cost, and social disruption. The definition of risk factors predicting graft success has facilitated the individualization of therapy within this integrated program. While allograft survival exceeding 90% may now be anticipated in the non-sensitized first-graft recipient, predicted outcome is poor in subjects who are highly sensitized following previous transplantation or with rapid loss of a prior graft.(ABSTRACT TRUNCATED AT 250 WORDS)

Graft Survival↗
PubMed1988

Effect of cyclosporine on insulin binding to erythrocytes in type 1 diabetes mellitus of recent onset.

The effect of cyclosporine (Cyclosporin A) on insulin binding to erythrocytes was investigated in Type 1 diabetes mellitus of recent onset. The subjects were drawn from a pilot study (The Canadian Open Study on the effects of immunosuppression with Cyclosporine in Type 1 Diabetes Mellitus) in which 50% of the patients demonstrated remission during one year of cyclosporine administration. Specific binding of 125I-insulin was examined before and after 3, 6, or 12 months of cyclosporine in different groups of patients. Those who maintained target control of blood glucose without exogenous insulin for two or more weeks were designated non-insulin requiring. Basal and intravenous glucagon-stimulated immunoreactive plasma C-peptide rose in all groups but to higher levels in non-insulin requiring groups. Insulin binding at tracer concentration, reflecting the number of insulin receptors, was initially normal but tended to decrease with duration of cyclosporine administration. This decrease was significant especially in groups which remained insulin-requiring throughout the study. The affinity of erythrocyte receptors was assessed by determining the insulin concentration required for 50% inhibition of 125I-insulin binding, the ID50. These values suggested that the affinity of insulin receptors was not affected in subjects attaining non-insulin requiring remission; however, in subjects remaining dependent on exogenous insulin, receptor affinity appeared to be adversely affected. Even in subjects who demonstrated complete remission, affinity was decreased during periods of dependence on exogenous insulin. After discontinuation of cyclosporine for one month or more, the mean daily insulin dosage increased and plasma C-peptide decreased. Insulin binding at tracer concentration was not affected but the apparent affinity was decreased after withdrawal of cyclosporine. These results suggest that insulin action at the receptor may be affected by the administration of cyclosporine. The number of insulin receptors appears to be decreased but whether this effect has an impact on insulin sensitivity remains to be seen. Receptor affinity appears to be affected mainly by exogenous insulin. Thus immunosuppression with cyclosporine in newly diagnosed Type 1 diabetes mellitus may have a modest adverse effect on insulin receptors; whether the benefits of cyclosporine treatment outweigh this risk is difficult to assess.

Diabetes Mellitus, Type 1↗