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Biomedical subjects

L Ost

Publications and source records attributed to L Ost.

At least 19 recordsLinked to original sources

Unsatisfactory effect of cyclosporin A treatment in Crohn's disease: a report of five cases.

Five patients with chronic continuous Crohn's colitis were treated with peroral Cyclosporin A (CyA) for 3 months in an open, uncontrolled pilot trial. The CyA dose was 10 mg kg-1 d-1 the first month of study, and thereafter 5 mg kg-1 d-1. Three of the patients initially showed some response to the treatment with decreases in the Crohn's disease activity index, but subsequently deteriorated. In one patient the condition was unchanged and another clearly worsened. Increases in serum creatinine levels were noted in three patients, and all of these also had decreased 51Cr-EDTA clearance indicating impaired renal function. Hypertrichosis and hyperaesthesia were also noted as side-effects. This study does not support the use of CyA in the short-term treatment of Crohn's disease in the colon.

Adult↗

A novel assay for pancreatic cellular damage: III. Use of a pancreas-specific protein as a marker of pancreatic graft dysfunction in humans.

Pancreas-specific protein (PASP) is a recently isolated and partially characterized major protein in the human pancreas. It has not been described previously. Serum levels of PASP and amylase were analyzed in 21 patients subjected to combined renal and segmental pancreatic transplantation with both organs obtained from the same donor and in eight kidney transplant patients. In the pancreas transplant patients, PASP and amylase levels were elevated in episodes of graft pancreatitis. With chronic graft rejection, PASP rose to high levels long before other indications. In episodes of renal rejection, the levels of PASP, but not always of amylase, were elevated on several occasions. They decreased after antirejection therapy. This may indicate accompanying pancreatic graft rejection. PASP and amylase levels were stable in kidney transplant patients and were not affected by serum creatinine levels, renal rejection, or antirejection therapy. The results support earlier observations that renal rejection in combined pancreas and renal transplant patients may or may not be accompanied by a rejection process in the pancreatic graft. PASP may be the means by which to tell when the pancreatic graft is involved.

Adult↗

Impaired glucose tolerance in cyclosporine-prednisolone-treated renal graft recipients.

In 33 renal transplant patients, an intravenous glucose tolerance test (IVGTT) was performed, and fasting plasma C-peptide concentrations analyzed. Nineteen of the patients were on treatment with cyclosporine-prednisolone (CsA-Po), and 14 were treated with azathioprine-prednisolone (Aza-Po). In the Aza-Po group, the K-values at IVGTT were normal in 13/14, but in the CsA-Po group they were only normal in 9/19 (P = 0.02). The fasting C-peptide levels were significantly higher in the CsA-Po group (P less than 0.001). within this group, there was no correlation between C-peptide level and serum-creatinine concentration, i.e. retention of C-peptide due to decreased renal function as judged by serum creatinine level was not suspected. Intrinsic prednisolone clearance was determined in the CsA-Po patients and was found to be lower than that previously described in Aza-Po patients. However, between those CsA-Po-treated patients with a pathologic K-value at IVGTT and those with a normal K-value there was no difference in prednisolone clearance, fasting C-peptide levels, CsA dose, or serum-creatinine concentrations. The pathophysiology of the cyclosporine-induced glucose intolerance is uncertain, and increased insulin resistance is possible.

C-Peptide↗

Hemorrhagic cystitis--a manifestation of graft versus host disease?

In 125 allogeneic bone marrow transplant recipients conditioned with cyclophosphamide (CY) with or without total body irradiation (TBI), three different protocols for prevention of CY urotoxicity have been used. The three protocols consisted of forced alkaline diuresis alone and then in combination with mesna (sodium 2-mercaptoethane sulfonate) at a low or high dose (60-90% and 150% of the CY dose, respectively). Hemorrhagic cystitis (HC) occurred in 21 patients: there were four immediate episodes without subjective symptoms which healed within a week after starting CY and 20 late episodes, starting between 17 and 51 (median 27) days. There was no correlation between the occurrence of HC and the different protocols used for prevention of urothelial toxicity. Late HC, however, except in one patient, always appeared together with acute graft-versus-host disease (GVHD) and the severity of the HC correlated with the severity of the GVHD (p less than 0.001). When acute GVHD commenced the HC started within 24 hours in three patients and in 11 patients when the dose of prednisolone given for an ongoing GVHD was reduced. In four other patients CY was not used for conditioning, but mustargen or melphalan in combination with TBI. In this group no urothelial protection was used. One of these patients developed a severe HC together with a grade II GVHD. Adenovirus and cytomegalovirus infections were not associated with HC.

Acute Disease↗

[20 years' experience with kidney transplantation in Stockholm].

Renal transplantations have now been carried out at our hospital for just over 20 years. The results have gradually improved and are now very satisfactory. There are many explanations for this development, but the improvement in immunosuppression has probably been the most crucial development. Renal transplantation is cheaper and it provides greater wellbeing for the patient than does chronic dialysis treatment. The indications have been widened and the number of patients waiting for a new kidney is increasing. An improved retrieval of cadaveric kidneys will be necessary for the required expansion of kidney transplantation programmes.

Cyclosporins↗

Impairment of prednisolone metabolism by cyclosporine treatment in renal graft recipients.

Pharmacokinetics of prednisolone were studied in 64 randomly chosen renal transplant patients treated with azathioprine and prednisolone (Aza-Po) or cyclosporine and prednisolone (CsA-Po). Intrinsic clearance for prednisolone was calculated after an oral test dose of 0.5 mg prednisolone/kg bodyweight. In 38 patients on Aza-Po treatment the mean clearance for prednisolone was 0.17 +/- 0.04 1/kg/hr (range 0.11-0.27) and in 39 patients on CsA-Po the mean prednisolone clearance was 0.12 +/- 0.02 (0.07-0.17) (P less than 0.001). Eight patients on CsA-Po were tested on three occasions; prednisolone clearance at 2-4 weeks was 0.13 +/- 0.02 (range 0.11-0.17), at 3-6 months 0.11 +/- 0.01 (0.10-0.12) and at 2-5 years 0.11 +/- 0.02 (0.09-0.14). In 11 patients the treatment was changed from Aza-Po to CsA-Po. The prednisolone clearance then decreased from 0.18 +/- 0.05 1/kg/hr (range 0.13-0.27) to 0.12 +/- 0.03 (0.10-0.16) (P less than 0.001). When the treatment was changed from CsA-Po to Aza-Po in 2 patients the prednisolone clearance increased from 0.12 and 0.10 to 0.17 and 0.12 1/kg/hr, respectively. These data show not only that the prednisolone metabolism is slower in cyclosporine-treated patients but also that this metabolism is retarded when azathioprine is replaced by cyclosporine, and that it is accelerated when cyclosporine is replaced by azathioprine. In the CsA-Po treated patients the prednisolone clearance was also found to be lower after 3-6 months than after less than one month (P less than 0.05) but there has been no further decrease in the prednisolone metabolism after up to more than 4 years of cyclosporine treatment.

Adolescent↗

Prednisolone excretion in human milk.

Six lactating women receiving long-term treatment with prednisolone in doses from 10 to 80 mg/day were studied. Serum and milk samples were assayed for prednisolone and endogenous cortisol by a specific high-performance liquid chromatographic method. The milk and serum concentrations vs time curves for prednisolone were virtually parallel, and the milk concentrations were 5% to 25% of those in serum. The milk/serum concentration ratio increased with increasing serum concentration. At a daily dose of 80 mg prednisolone, the infant would ingest less than 0.1% of that dose; this corresponds to less than 10% of the infant's endogenous cortisol production. Because there is an equilibrium between the concentration of prednisolone in milk and serum, the exposure of the infant is minimized if breast-feeding is avoided during the first 4 hours after the dose. We conclude that from a quantitative point of view the exposure of the infant is minimal, and breast-feeding may be permitted at maternal prednisolone doses of at least 20 mg once or twice daily. At higher doses, exposure may be minimized if nursing is performed greater than 4 hours after the dose.

Female↗

Clinical value of assessing prednisolone pharmacokinetics before and after renal transplantation.

The value of assessing the kinetics of prednisolone for predicting graft survival and the occurrence of adverse effects of long-term treatment with prednisolone was evaluated in 35 renal transplant patients. The subjects were given an oral test dose of 30 mg prednisolone before, shortly after and 3 months after transplantation. Serum samples were assayed for prednisolone and endogenous hydrocortisone by a specific HPLC method. Intrinsic prednisolone clearance differed less than three-fold (range 0.10-0.27 l/kg X h) between the patients and was relatively stable at different times in each of them. From the data obtained it was not possible to predict rejection episodes. If rejection occurred, however, a high clearance (greater than or equal to 0.20 l/kg X h) appeared to be deleterious for the outcome (p less than 0.05). Patients with Cushingoid habitus did not differ from non-Cushingoid patients with respect to prednisolone clearance or endogenous hydrocortisone level. 7 out of 8 cases of steroid-related complications (steroid diabetes, psychosis, duodenal ulcer, perforation of the colon and osteonecrosis) occurred in patients with a clearance lower than 0.16 l/kg X h (ns). The one-year graft survival rate was 67% in patients with a clearance greater than or equal to 0.16 l/kg X h, compared to 85% in patients with a lower clearance (ns). Although some correlation may exist between prednisolone kinetics, graft survival and steroid-related complications (not statistically significant in the present study), the predictive value of prednisolone kinetics is probably small in routine clinical work.

Adult↗