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Biomedical subjects

D M Canafax

Publications and source records attributed to D M Canafax.

105 records · Page 6Linked to original sources
PubMed1985

A single institution, randomized, prospective trial of cyclosporin versus azathioprine-antilymphocyte globulin for immunosuppression in renal allograft recipients.

Between September 26, 1980 and December 31, 1983, 230 splenectomized, transfused renal allograft recipients were randomized to treatment with either cyclosporin-prednisone (N = 121, 68 diabetic and 53 nondiabetic recipients; 73 cadaver and 48 related donor grafts) or azathioprine-prednisone-antilymphocyte globulin (N = 109, 61 diabetic and 48 nondiabetic recipients; 69 cadaver and 40 related donor grafts). The results were analyzed on March 31, 1984. Actuarial patient survival rates at 2 years were 88% in the cyclosporin and 91% in the azathioprine groups (p = 0.649). Graft survival rates at 2 years were 82% in all cyclosporin and 77% in all azathioprine-treated recipients (p = 0.150); the corresponding figures in the recipients of related donor grafts were 87% vs. 83% (p = 0.656), and in the recipients of cadaver donor grafts were 78% vs. 73% (p = 0.178). The 2-year graft survival rates were 81% in cyclosporin and 74% in azathioprine-treated diabetic recipients (p = 0.150) and 83% in cyclosporin and 81% in azathioprine-treated nondiabetic recipients (p = 0.604). Within the cyclosporin and azathioprine treatment groups, the differences in graft survival rates between diabetic and nondiabetic recipients were not significant (p = 0.822 and 0.423, respectively). Although there were no significant differences in graft survival rates, the cumulative incidence of rejection episodes within the first post-transplant year was significantly lower in the cyclosporin (34%) than in the azathioprine (60%) treated recipients (p = 0.001). In recipients of technically successful cadaver kidney grafts, the incidence of acute tubular necrosis (ATN) was 31% in cyclosporin and 30% in azathioprine-treated recipients (p = 0.822). Graft survival rates in azathioprine- and cyclosporin-treated recipients who did or did not undergo ATN were 72% vs. 89% (p = 0.011). The mean (+/- S.D.) serum creatinine levels (mg/dl) at 1 year were higher in cyclosporin (2.0 +/- 0.6) than in azathioprine (1.5 +/- 0.5) treated recipients (p = less than 0.001). A reduction in cyclosporin dose because of nephrotoxicity was required in 96 of the cyclosporin-treated patients (70%), and 25 were switched to treatment with azathioprine (21%). The incidence of all infections in cyclosporin-treated patients was approximately half of that in azathioprine-treated patients, and only nine per cent of the cyclosporin-treated patients were diagnosed to have cytomegalovirus infections during the first post-transplant year vs. 28% in azathioprine-treated patients (p = 0.002).(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1983

The use of a cosyntropin stimulation test to predict adrenal suppression in renal transplant patients being withdrawn from prednisone.

Eighteen renal transplant patients were studied to identify predictors of steroid-induced adrenal suppression. A cosyntropin adrenal stimulation test was administered to each patient and the response was correlated with the past transplant course and their subsequent prognosis. Eight (44%) of the 18 patients studied had a suppressed cosyntropin stimulation test. The suppressed adrenal response could not be predicted accurately by any one factor, although a history of a total prednisone dose greater than 25 g or a duration of steroid therapy of more than 12 months occurred more often among the suppressed patients. Four of the five deaths occurred among the suppressed patients. These deaths occurred despite maintenance of steroid administration. The cosyntropin stimulation test can be easily performed to identify renal transplant patients at risk of steroid-induced adrenal suppression when rapid steroid tapering is desired. An unsuppressed response gives assurance that steroid withdrawal is safe.

Adolescent↗
PubMed1983

Effect of pH on disintegration and dissolution of ketoconazole tablets.

The effect of pH on the in vitro disintegration, dissolution, and solubility of ketoconazole tablets was studied. One 200-mg ketoconazole tablet was added to each of five different buffer solutions having pH values of 2 to 6;900 ml of each solution containing the ketoconazole was placed in a stationary basket dissolution device and stirred at 500 rpm at 37 degrees C for 60 minutes. Single 1-ml samples of each solution were obtained at 1,3, and 5 minutes after addition of the drug, and then every 5 minutes for the duration of the sampling period. This same procedure was repeated using two 200-mg tablets in the buffer solution at pH 3. The effect of pH on ketoconazole solubility was studied by gradually increasing the pH of a ketoconazole solution at pH 3 to pH 10. Samples of this solution were analyzed periodically after allowing a short period for equilibration of pH. All samples were assayed spectrophotometrically against blanks, and concentrations were determined by comparison with a standard curve. Disintegration of ketoconazole tablets occurred within 5 minutes in each buffer solution and was unaffected by pH. At pH 2 and 3, dissolution of ketoconazole was greater than 85% complete after five minutes, and all ketoconazole had dissolved after 30 minutes. As pH increased, the rate and extent of dissolution slowed; only 10% of ketoconazole was dissolved after 60 minutes at pH 6. Ketoconazole precipitated rapidly from solution as the pH of the dissolution medium exceeded 5.5. There was no difference in the rate or extent of dissolution of ketoconazole for the two doses studied at pH 3. In the buffer solutions tested, dissolution but not disintegration of ketoconazole tablets is pH-dependent. Dissolution characteristics of 200- and 400-mg doses of ketoconazole are similar at pH 3.

Hydrogen-Ion Concentration↗
PubMed1982

Aminoglycoside dosing in renal transplant patients. Comparison of nomogram and individualized pharmacokinetic methods in patients with shifting renal function.

Serum amikacin concentrations were compared in infected renal transplant recipients that were compared in infected renal transplant recipients that were dosed using a creatinine-based nomogram (group I) or an individual computer-assisted pharmacokinetic dosing method (group II). A total of 30 treatment courses were administered. Mean postinfusion peak levels were 22 microgram/ml in group I and 23.4 microgram/ml in group II. Mean serum trough levels were 8.8 microgram/ml and 5.5 microgram/ml in groups I and II, respectively. Both peak and trough serum levels were significantly more often in the acceptable therapeutic (peak 20-32 microgram/ml) and nontoxic (through less than 10 microgram/ml) ranges in group 11 patients. Seventy-seven per cent of group II and 38% of group I peak levels were in the therapeutic range, while 87% of group II and 70% of group I trough levels were less than 10 microgram/ml. Ototoxicity developed with similar frequency in both groups and occurred significantly more often with a peak level greater than 32 microgram/ml. Declining renal function, usually as a result of allograft rejection, occurred in seven (44%) group I and only three (25%) group II patients but could not be exclusively related to amikacin in any patient. A serum trough level of greater than 10 microgram/ml was associated with an increased risk of declining renal function independent of other risk factors. Failures of aminoglycoside therapy are frequently associated with inadequate serum levels. Conversely, ototoxicity and nephrotoxicity may be related to elevated serum aminoglycoside concentrations. For these reasons, the computer-assisted pharmacokinetic dosing method should be used in septic surgical patients whose renal function is subject to sudden and unexpected changes.

Adolescent↗
PubMedDate not supplied

Increased dosage requirements of tobramycin and gentamicin for treating Pseudomonas pneumonia in patients with cystic fibrosis.

The pharmacokinetic behavior of tobramycin and gentamicin was evaluated in 27 patients who had cystic fibrosis (CF). A previously studied, age-matched group of 334 patients who had been treated with gentamicin and who did not have CF served as controls. The CF patients, who ranged in age from 2 to 32 years and who had normal renal function, received 36 treatment courses with either tobramycin (19) or gentamicin (17) to treat Pseudomonas pneumonia. Serum concentrations were determined after a 1.5-mg/kg dose to compute half-life (t 1/2), elimination rate constant (k), and apparent volume of distribution (V). From these values, doses were calculated to produce steady-state peak concentrations of 8.0 micrograms/ml with a dosing interval of every six hours. For tobramycin the mean (+/- SD) t1/2 was 1.0 (0.4) hours, V was 0.18 (0.06) l/kg, total body clearance (TBC) was 2.19 (0.71) ml/min/kg, and the calculated dose was 8.2 (2.1) mg/kg/day. For gentamicin t1/2 was 1.1 (0.5) hours, V was 0.20 (0.06) l/kg, TBC was 2.28 (0.89) ml/min/kg, and the calculated dose was 8.8 (2.4) mg/kg/day. The pharmacokinetic parameters were not statistically different between the two drugs, but the mean values of t1/2 and TBC of CF patients differed significantly from those of the control group. The calculated doses were larger than the manufacturer's maximum recommended dose of 7.5 mg/kg/day for 63% of tobramycin and 71% of gentamicin treatment courses. A dosing interval change to every four hours would have been appropriate in 28 of the 36 treatment courses (78%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMedDate not supplied

Renal transplantation in diabetic patients is confirmed therapy while pancreas transplantation should be performed only in an investigational setting.

Kidney transplantation is now firmly established as the standard treatment for all diabetic patients with end-stage renal failure. In an analysis of all renal transplants at the University of Minnesota between June 1, 1980 and May 31, 1987, there were no differences in renal allograft functional survival rates for diabetic and nondiabetic recipients. At one year the survival rates were 84% (n = 151) and 86% (n = 260) for those treated with azathioprine, prednisone and ALG; 86% (n = 101) and 87% (n = 104) for those treated with cyclosporine-prednisone, and 92% (n = 165) and 89% (n = 191) for those treated with triple therapy (cyclosporine, azathioprine, and prednisone). Pancreas transplantation remains an investigational procedure for nonuremic diabetic patients but may be considered therapeutic in diabetic renal allograft recipients because such patients are obligated to immunosuppression and only the surgical risks of pancreas transplantation need to be considered, which are now acceptably low. Recipients of pancreas transplants performed simultaneous with the kidney have patient and pancreas graft survival rates of greater than 90% and +/- 60% at several institutions, including our own. The potential for benefit of pancreas transplantation, however, is greater in the nonuremic nonkidney transplant patient, and pancreas transplantations are being performed in such patients at a few institutions. An early beneficial effect of pancreas transplantation preexisting proliferative retinopathy has not been discerned, although long-term retinopathy has been stable in patients with functioning grafts. Preliminary studies have shown a beneficial effect on neuropathy and on microscopic lesions of diabetic nephropathy, but at the expense of cyclosporine toxicity.(ABSTRACT TRUNCATED AT 250 WORDS)

Diabetes Mellitus, Type 1↗
PubMedDate not supplied

Cyclosporine immunosuppression.

The chemistry, pharmacokinetics, mechanism of action, clinical efficacy in organ transplants, adverse effects, and dosage and administration of cyclosporine, a new immunosuppressant, are reviewed. Advice on counseling patients who take the drug is also included. Cyclosporine is a cyclic undecapeptide with a high molecular weight. Its absorption from the gastrointestinal tract is slow, variable, and incomplete. Cyclosporine is highly protein bound and almost completely eliminated by hepatic metabolism. Its half-life is variable, and it has a volume of distribution of approximately 4 liter/kg and a poorly defined therapeutic range. Cyclosporine acts by blocking T-lymphocyte function without causing myelosuppression. Several randomized prospective trials have compared cyclosporine with standard immunosuppressive drug regimens in kidney and liver transplantations. A European Multicenter Trial treated 117 patients with cyclosporine alone and 115 patients with azathioprine and steroids. Graft survival rates at 11 months were 73% in the cyclosporine group and 53% in the control group. A Canadian Multicenter Trial Group, which studied 209 patients in two groups, found cyclosporine and prednisone to be superior to azathioprine and prednisone therapy. Graft survivals were 83.5% and 67% at nine months. Several studies of hepatic allograft recipients and of cardiac transplantations have found that cyclosporine and low-dose steroid therapy can lead to improved results. The adverse effects of cyclosporine include nephrotoxicity, hepatotoxicity, and electrolyte elevations. The dosage must be individualized. Most patients tolerate initial i.v. doses of 5 mg/kg and oral doses of 14-18 mg/kg. The exact indications for cyclosporine immunosuppression are still being defined for organ transplant recipients. Cyclosporine will likely play an important role in the improvement of transplantation results in the future.

Animals↗