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I Karlberg

Publications and source records attributed to I Karlberg.

At least 37 records · Page 2Linked to original sources

Renal retransplantation in patients with HLA-antibodies.

The results of 92 consecutive renal retransplantations, performed during a 5-year period in recipients with HLA-antibodies, were retrospectively analysed. The actuarial 1-year graft survival (1-y GS) was 65% for all retransplantations, as compared with 63% for first grafts in sensitized recipients. For the second (n = 56), third (n = 24) and fourth-fifth (n = 12) grafts 1-y GS was 64%, 71% and 58%, respectively. Acute rejection was the major cause of graft loss (45%). Recipients with > 3 years GS of the preceding transplant had significantly better GS at retransplantation. Also, grafts with no HLA mismatches had significantly prolonged GS. One-y GS was 78% when PRA (panel reacting antibody) was less than 50%, and 60% when PRA was more than 50%. A benefit of repeated mismatches was demonstrated in the subgroup with PRA < 50%, in contrast to recipients with PRA > 50%, suggesting that, in some patients, an absence of antibody response against certain antigens might be used as a basis for future deliberate mismatching.

Female↗

Adjuvant treatment with ursodeoxycholic acid prevents acute rejection in rats receiving heart allografts.

Adjuvant treatment with ursodeoxycholic acid (UDCA) for liver-transplant recipients has been reported to reduce the frequency of acute rejection episodes. To explore this effect further, UDCA was given to rats in an experimental heart transplantation model, with or without concomitant immunosuppressive treatment with antihymocyte globulin (ATG). UDCA was administered orally 7 days before and 14 days after transplantation. Rats treated with UDCA alone or in combination with ATG were compared with untreated controls and ATG-treated recipients. Adjuvant treatment with UDCA was found to induce prolonged graft survival and increase the amount of transplant tolerance in rats. Serum levels of bilirubin and aminotransferases were not altered irrespective of the UDCA dose given. The results indicate that UDCA has an immunomodulatory capacity that might not be restricted to the liver, but also might apply to other transplanted organs as well.

Animals↗

The bile acid independent flow is reduced in the transplanted liver.

Bile secretion is an important indicator of liver graft function. Reports on bile formation by the transplanted liver with stable function some months after operation are scarce. In this study bile flow, bile salt secretion rate (BSSR) and biliary clearance of polyethylene glycol (PEG) 900, a marker of canalicular bile flow, were studied in a group of liver-transplanted (LTX) patients (n = 8) 3-6 months after transplantation. A group of cholecystectomized patients with indwelling T-tubes (n = 6) served as a control group. Both groups were treated with oral ursodeoxycholic acid (500 mg/day). On the day of the study bile was drained for 6 h by gravity and four-hourly samples were used in the calculations. The relation between bile flow and BSSR analysed with linear regression showed a reduced bile acid independent flow in the liver-transplanted group (0.11 ml/min) compared with the control group (0.20 ml/min). The relation between biliary clearance of PEG 900 and BSSR showed a significantly steeper slope for the cholecystectomized control patients (1.40 ml/micromol) compared with the liver-transplanted patients (0.30 ml/micromol). We conclude, that in spite of stable graft function with normal liver enzmyes, the transplanted liver has a reduced bile acid independent bile flow. The transplanted liver also has a reduced biliary clearance of PEG 900 indicating a reduced canalicular bile flow. The cause of this impaired bile formation could be due to the influence of the immunosuppressive drug cyclosporin, the result of damage to the liver during preservation and reperfusion or the continuous immunological challenge to the graft.

Adult↗

Adjuvant treatment with ursodeoxycholic acid reduces acute rejection after liver transplantation.

Acute rejection, occurring with a reported frequency of 50-70%, is still a dominating problem after liver transplantation. Medication with ursodeoxycholic acid (UDCA) has beneficial effects in different cholestatic conditions and has also been shown to reduce HLA class I antigen expression on hepatocytes in patients with PBC. Since August 1989 we have consecutively treated all patients with primary graft function with UDCA (n = 41). Patients transplanted in the first half of 1989 served as a control group (n = 8). All patients in this study were given sequential quadruple drug immunosuppression. The treatment group were given oral UDCA 10 mg/kg per day. During the first postoperative month, 17% of the UDCA-treated patients had an episode of acute rejection compared with 75% of the control patients (P < 0.01). Liver biochemistry tests 1 month postoperatively were significantly better in patients treated with UDCA. The results suggest that adjuvant treatment with UDCA reduces acute liver graft rejection.

Acute Disease↗

Cytochrome c oxidase and purine nucleotides in skeletal muscle in tumour-bearing exercising rats.

We have previously shown that spontaneous physical exercise can delay the onset of experimental anorexia and cachexia and retard tumour growth and we now report the effects on the energy metabolism in skeletal muscle. Exercising tumour-bearing animals (TBE) had an increased maximal capacity for oxygen uptake expressed as Vmax of the cytochrome c oxidase compared with their tumour-bearing sedentary controls (TBS) [mean (S.E.) 289.9 (30.7) vs. 141.6 (11.0); P less than 0.05] but an unchanged Km value. The TBS animals had a depressed Vmax as compared with non-tumour-bearing sedentary controls (CS) [141.6 (11.0) vs. 210.1 (15.1); P less than 0.05]. Most of the purine nucleotides in the 'glycolytic' anterior tibial muscle were significantly altered in the TBE animals compared with the TBS animals, but in the mainly 'oxidative' soleus muscle only the level of inosine monophosphate (IMP) was changed. The results indicate that physical exercise can normalise the oxidative capacity and improve the energy state in skeletal muscle in the tumour-bearing host.

Animals↗

A randomized trial of cyclosporine and prednisolone versus cyclosporine, azathioprine, and prednisolone in primary cadaveric renal transplantation.

A randomized trial was performed with the aim to compare two immunosuppressive treatment schedules in adult recipients of first cadaveric renal transplants. A total of 229 patients were randomized to double therapy with cyclosporine and prednisolone and 234 patients were randomized to triple therapy with cyclosporine, azathioprine, and prednisolone. Minimum follow-up was 4 years. The actuarial 5-year patient survival was 79.8% in the double therapy group and 82.3% in the triple therapy group (n.s.). The corresponding graft survival figures were 54.4% and 59.6% in the two groups, respectively (n.s.). There were no differences between the groups regarding cause of death or cause of graft loss. Renal function as determined by serum creatinine did not differ between the groups and was stable throughout the observation period. Azathioprine was instituted in a total of 51 patients randomized to double therapy. This subgroup of patients had a patient and graft survival not different from the remaining patients randomized to double therapy or from the patients randomized to triple therapy. There were no differences between the double and triple therapy groups regarding incidence and timing of acute rejection or infections. The incidence of other medical diseases and adverse events such as nephrotoxicity or malignancy did not differ between the groups. Azathioprine-induced leukopenia was uncommon (19 episodes in the triple therapy group). In a multivariate analysis of the whole series the only covariates that significantly influenced graft survival were age of recipient and occurrence of acute rejection, while among other factors treatment schedule did not. Thus this prospective study, in accordance with previous such studies, failed to find support for the use of triple therapy as first choice immunosuppression in first cadaveric renal transplantation. However, the study could not rule out the possibility that some patients at risk for the development of irreversible rejection or nephrotoxicity of CsA might benefit from the addition of azathioprine to the treatment schedule.

Adult↗

Glomerular volume in kidneys transplanted into diabetic and non-diabetic patients.

Biopsies taken at the time of renal transplantation in 12 non-diabetic and 23 diabetic patients were studied by quantitative light- and electron-microscopy. Repeat biopsies were taken at 6 months and/or after 2-3 years in patients who had acceptable graft function. All patients except two received cyclosporin as part of the immunosuppression. Glomerular volume was significantly increased, + 36(95% CI +6 to +65) % (p = 0.03), in the diabetic patients at 6 months which differed from the change of -20 (-50 to +10) % in the non-diabetic patients (p = 0.03). After 2-3 years glomerular volume was equal to the baseline value in the diabetic patients, while the change from baseline in the non-diabetic patients was -21 (-42 to -1) %. Substantial glomerular occlusion was seen in only three diabetic patients after 2-3 years. Total structural volumes per glomerulus in the 2-3-year biopsies showed an increase in basement membrane material of 0.09 x 10(6) microns 3 in the diabetic patients, significantly different from the change in non-diabetic patients (-0.10 x 10(6) microns 3, p = 0.003). No correlation was obtained between the 6-month increase in glomerular volume and the development of diabetic glomerulopathy at 2-3 years. The fact that glomerular hypertrophy was not present in the entire series may be due to the cyclosporin and to rejection. Nevertheless the diabetic group did show an early hypertrophy which did not seem to play a major role in the ensuing development of diabetic glomerulopathy.

Adult↗