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Biomedical subjects

A Laupacis

Publications and source records attributed to A Laupacis.

At least 145 records · Page 8Linked to original sources
PubMed1989

A technology assessment study design.

Randomized controlled trials of drug therapies are now required before the licensing and use of almost all medications. Other health care technologies should be similarly evaluated. The area of competing technologies requires more research, and cemented and noncemented hip prostheses have recently been identified as an important example of such a technology. Although trials such as ours require considerable care in their planning and execution, they can be conducted on a busy clinical teaching ward without adversely affecting the quality and quantity of clinical care.

Bone Cements↗
PubMed1989

Randomized trials in orthopaedics: why, how, and when?

There is increasing recognition that major new medical therapies should be rigorously evaluated before they are put into general clinical use. Randomized controlled trials provide the most unbiased assessment of the risks and benefits of such therapies. In this article, the most important aspects of the design and execution of a randomized clinical trial in orthopaedics are discussed. These include the reasons for and mechanisms of randomization, appropriate selection of patients and therapy, reasons for the blinding of therapy, types of measures of outcome that can be used, aspects of sample-size calculation and analysis of data, and ethics of randomized controlled trials.

Cementation↗
PubMed1987

Effects of cyclosporine in recent-onset juvenile type 1 diabetes: impact of age and duration of disease.

Administration of cyclosporine resulted in reduced insulin requirements and improved glycemic control in patients with insulin-dependent diabetes mellitus of recent onset, but the drug was less effective in young children. Renal toxic effects and other problems related to therapy resolved after discontinuation of the drug. Sustained remission seemed dependent on continued administration of cyclosporine. Although short-term control of diabetes may be achieved in some patients, more studies are needed to determine whether cyclosporine can be given safely as maintenance therapy to maintain glycemic control and prevent the long-term consequences of the disease.

Adolescent↗
PubMed1984

Effects of cyclosporine immunosuppression in insulin-dependent diabetes mellitus of recent onset.

Type I diabetes may be an autoimmune disorder, although the evidence is largely circumstantial. The natural history of the disease after diagnosis includes partial remission in most patients, but only about 3 percent achieve transient insulin independence. beta Cell function, as indicated by the plasma concentration of C-peptide, is lost over 6 to 30 months and islet cell antibodies disappeared over 1 to 2 years. This article describes a pilot study in which 41 patients were treated with the immunosuppressive agent cyclosporine for 2 to 12 months. Of 30 patients treated within 6 weeks of diagnosis, 16 became insulin independent with concentrations of plasma C-peptide in the normal range and decreasing titers of islet cell antibodies. Of 11 patients who entered the study 8 to 44 weeks after diagnosis, two achieved this state. These results indicate that a controlled trial of the effects of cyclosporine in type I diabetes should be conducted.

Adolescent↗
PubMed1984

Evaluation of cyclosporin-phenytoin interaction with observations on cyclosporin metabolites.

We have observed that patients on concurrent cyclosporin and phenytoin therapy required increased doses of cyclosporin to maintain therapeutic concentrations of this novel immunosuppressive drug. We have, therefore, studied the influence of phenytoin on the pharmacokinetics of oral cyclosporin in six healthy male subjects. Cyclosporin concentrations in serum and whole blood were measured by high pressure liquid chromatography (h.p.l.c.) and radioimmunoassay (RIA). Concentrations of cyclosporin in whole blood were consistently higher than corresponding values in serum. Concentrations of cyclosporin determined by RIA were also consistently higher than those determined by h.p.l.c. Irrespective of the biological fluid (serum or whole blood) or the type of drug analysis (h.p.l.c. or RIA), changes in cyclosporin kinetics following phenytoin administration exhibited similar patterns. Phenytoin significantly reduced the maximum concentration and the area under the concentration-time curve and significantly increased total body clearance of cyclosporin. There was a statistically significant reduction of cyclosporin half-life (t 1/2) in whole blood using h.p.l.c. analysis. However, there was no significant change in cyclosporin t 1/2 in serum following phenytoin administration, using either form of drug analysis. Cyclosporin metabolites 17 and 18 were measured by h.p.l.c. in whole blood samples only, since these metabolites were found almost entirely in red blood cells. Phenytoin significantly reduced the Cmax and AUC of both metabolites, but no significant change was observed in the t 1/2 of either. Phenytoin enhanced the metabolism of antipyrine which was co-administered with cyclosporin to assess oxidative enzyme activity. We conclude that patients undergoing organ transplantation should be carefully monitored if they require phenytoin or other drugs known to accelerate oxidative metabolism.

Adult↗
PubMed1983

Cyclosporin prevents diabetes in BB Wistar rats.

Cyclosporin (U.S.A.N. cyclosporine) was used prophylactically to suppress the development of insulin-dependent diabetes mellitus in BB Wistar rats. In this rat strain diabetes spontaneously develops between 60 and 120 days of age and this condition resembles human type 1 diabetes. In 30 (75%) out of 40 control rats glycosuria and hyperglycaemia developed and these rats became insulin-dependent. Their pancreases showed partial to complete destruction of the islets of Langerhans by lymphocytic infiltration. None of the 40 cyclosporin-treated rats became diabetic and their pancreases were histologically normal. Serum cyclosporin was monitored in a subgroup and the dosage was adjusted accordingly; neither hepatotoxicity nor nephrotoxicity was seen in the treated animals.

Animals↗
PubMed1983

Cyclosporine: action, pharmacokinetics, and effect in the BB rat model.

Cyclosporine (Cy) was given to BB rats in an attempt to prevent the onset of diabetes. A dose of 15 to 20 mg/kg/d given orally or subcutaneously was associated with high Cy trough serum levels and caused nephrotoxicity and severe weight loss. Ten mg/kg/d of Cy was tolerated well. Forty rats were treated with Cy starting at 34 days of age. No Cy-treated rats developed diabetes by day 121, compared with 70% of the control rats. Once Cy was discontinued on day 121, 38% of female and 13% of male rats developed diabetes by day 169. Transient, spontaneously remitting hyperglycemia developed in nine rats. This occurred both in control rats and in rats on Cy, but it was more common in females than in males. Thus, Cy prevents diabetes mellitus in the BB rat when trough Cy serum levels greater than 100 ng/mL are achieved. Diabetes occurs in some rats after Cy is discontinued. In all treatment subgroups, diabetes occurred more frequently in females than in males.

Animals↗
PubMed1983

Renal allograft survival in the baboon using a pretreatment protocol with cyclosporine.

Cyclosporine extends kidney allograft survival in the chacma baboon, and this study explores various administration protocols to generate optimal serum concentrations of the drug, assessed by radioimmunoassay and by inhibition of lymphocyte transformation by phytohemagglutinin and allogeneic lymphocytes in culture. Serum levels commensurate with concentrations that have been shown to be immunosuppressive in humans (150-400 ng/ml) are reached after 14 days of pretreatment with 10 mg cyclosporine/kg, and after 7 days with 20 and 30 mg cyclosporine/kg. The 10-mg dose prolongs median graft survival from 11 to 21 days, which is the same as that obtained with 20 mg/kg administered after transplantation. Further increases in the pretreatment dose to 20 or 30 mg/kg result in survivals of 27 and 31 days, respectively. All the animals died from rejection during therapy and the T-cell-binding avidity, and absorptive or degradative processes may necessitate doses far in excess of those currently used in transplantation.

Absorption↗
PubMed1983

Simplified liquid-chromotographic analysis for cyclosporin A, and comparison with radioimmunoassay.

We describe a simplified isocratic "high-performance" liquid-chromatographic method for measuring a new immunosuppressive drug, cyclosporin A, in biological fluids with use of its analogs cyclosporin C and cyclosporin D as internal standards. The method is reproducible and accurate and appears to be specific for cyclosporin A; the detection limit is 31 micrograms/L. The chromatographic measurements of the concentration of cyclosporin A in serum of patients receiving the drug were invariably lower than those by radioimmunoassay and the difference became more pronounced the greater the period of time after dosing. Because measurements of cyclosporin A in serum standards were almost identical with both techniques, the differences between the two sets of results for patients' samples suggests that the radioimmunoassay is nonspecific and measures metabolites of cyclosporin A.

Adult↗
PubMed1983

CT findings in postpartum renal cortical necrosis.

A 34-year-old woman presented with postpartum renal cortical necrosis. Contrast-enhanced computerized tomography (CT) of her kidneys showed a narrow subcapsular band of increased density that was separated from the medulla by a distinct band of decreased density. This is analogous to the decreased cortical nephrogram seen on arteriography. The CT scan may be a useful, non-invasive diagnostic procedure in renal cortical necrosis.

Acute Kidney Injury↗