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J Ahonen

Publications and source records attributed to J Ahonen.

At least 145 records · Page 8Linked to original sources

Mechanisms of insulin resistance after kidney transplantation.

In order to study the effect of corticosteroids on energy metabolism in immunosuppressed patients after kidney transplantation, we have examined glucose utilization, energy expenditure, and lean body mass in 10 kidney-transplanted patients receiving steroids (methylprednisolone 8.2 +/- 1.5 mg/day) and in 10 healthy age- and weight-matched control subjects. Glucose utilization was measured during euglycemic insulin clamp in combination with indirect calorimetry and infusion of [3H-3]-glucose, while beta-cell function was measured during a hyperglycemic clamp. The kidney-transplanted patients were resistant to the glucoregulatory effect of insulin, as demonstrated by a 25% reduction in total glucose disposal compared to control subjects. This defect was almost completely accounted for by a defect in storage of glucose as glycogen (3.3 +/- 0.5 vs. 5.0 +/- 0.5 mg/kg LBM min; P less than 0.05). The reduction in nonoxidative glucose disposal was associated with reduced lean body mass and incapacity to release energy as heat after infusion of insulin, i.e. thermogenic defect. In contrast, oxidation of glucose and lipids was not influenced by steroid therapy. Furthermore, suppression of hepatic glucose production was normal, and insulin secretion was normally enhanced in relation to the degree of insulin resistance in the steroid-treated patients. In conclusion, steroid-induced insulin resistance in kidney-transplanted patients is due to alterations in the nonoxidative pathway of glucose metabolism. These findings raise the question of whether steroid therapy directly influences glycogen synthase in man.

Adrenal Cortex Hormones↗

Diagnosis of acute rejection in liver transplantation.

Eleven acute rejections were found in 9 patients with liver transplantation due to end-stage liver cirrhosis. The rejections were diagnosed with fine-needle aspiration biopsy (FNAB) giving the cellular picture of immunoactivation in the liver graft when compared to a simultaneous sample of peripheral blood. s-Alkaline phosphatase and s-bilirubin increased within 1 week after onset of rejection in 7 and 10 cases, respectively. s-Alanine amino-transferase and b-ammonium were of no value in the diagnosis of acute rejection. A core biopsy was obtained only in a case of severe liver damage, mainly to estimate the need for retransplantation. One year after grafting, 6 out of 7 cirrhotic patients are well, all with normal liver function. Two have died of sepsis. One patient died from pulmonary metastases of occult liver carcinoma 6 months after the transplantation. FNAB seems helpful in detecting early acute rejection and also excluding such an event in the liver graft.

Alkaline Phosphatase↗

Fine-needle aspiration biopsy in the monitoring of liver allografts. II. Applications to human liver allografts.

Serial fine-needle aspiration biopsies (FNAB) were used for clinical monitoring of human liver allografts. Nine liver allograft recipients were monitored with FNAB at 1-3 day intervals. No complications were recorded. All patients underwent at least 1 inflammatory episode of acute rejection; altogether 11 episodes, all reversible, were recorded. The inflammatory infiltrate consisted mainly of lymphoid cells, including lymphoid blasts, with minor involvement of monocytes, monoblasts, and macrophages. Further analysis of lymphoid cell subpopulations by immunoperoxidase techniques demonstrated an increase of T cells during rejection, both the CD4 (T4) and CD8 (T8) subsets were increased. A slight increase of B cells in the graft was also seen. The CD4/CD8 (T4/T8) ratio was first low, peaked at the onset, and decreased toward the end of the episode. No clear correlations to the intragraft cellular events were recorded in corresponding blood specimens. However, an episode of eosinophilia was seen in the blood at the beginning of rejection, correlating with fever in the recipient. Degenerative changes in the parenchymal cells and bile droplets in the hepatocytes, indicating cholestasis and hepatocyte damage, were seen during all episodes of rejection, and these changes persisted even 10 days after the inflammation had subsided. The FNAB-findings correlated well with biochemical laboratory parameters, but the diagnosis of rejection could be established by the FNAB already 1-5 days earlier than elevated serum values indicated liver dysfunction.

Alkaline Phosphatase↗

Effects of cyclosporine, azathioprine, and steroids on the renal transplant, on the cytologic patterns of intragraft inflammation, and on concomitant rejection-associated changes in recipient blood.

We have investigated the impact of various immunosuppressive drugs and their combinations on the graft, on the intragraft inflammatory patterns of rejection, and on rejection-associated effects in the recipient circulation by fine-needle aspiration biopsy and an extensive computer program. The patients were randomized into three treatment groups, 32 patients each, with the following postoperative immunosuppression: (1) Aza (2.1 mg/kg/d) plus MP (3.6 mg/kg/d tapered to 0.5 mg/kg/d by day 15), (2) CsA (10 mg/kg/d tapered to 8 mg/kd/d by day 28) and, (3) CsA (as above) plus MP (3.6 mg/kg/d tapered to 0 mg/kg/d by day 9). The groups were homogeneous in regard to all tested pretransplantation parameters. Graft parenchymal cell morphology was significantly (P less than .05) deteriorated and urine output reduced in CsA-treated patients, compared to those receiving Aza + MP; concomitant administration of steroids partially (P = NS) protected against the CsA-associated effects. The first episode of inflammation occurred significantly earlier (P less than .001) in patients receiving initially only CsA, compared to those receiving Aza + MP or CsA + MP, the total duration of intragraft inflammation was longer and the clinical signs of rejection were significantly prolonged (.001 less than P less than .05). Although the influx of lymphocytes and monocytes into the graft and the peak intensity of intragraft inflammation was similar in the three groups of patients, the inflammatory patterns of rejection were distinctly different. The number of (T) lymphoblasts in CsA-treated grafts was significantly (P less than .05) lower and their appearance delayed, compared to those treated with Aza + MP and even lower and more delayed in grafts treated initially with CsA + MP. The number of (B) plasmablasts was also reduced and their appearance delayed, but the differences to conventional treatment with Aza + MP were smaller and no longer significant. On the other hand, a significant (P less than .01) early maturation of blood-borne monocytes into tissue macrophages was observed in the CsA-treated grafts in context of first rejection, which was lacking from those treated with CsA + MP or Aza + MP. In the blood, the first episodes of inflammation under CsA were associated with significant (P less than .001) thrombocytosis, which was lacking from the Aza + MP- and CsA + MP-treated patients.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

Outcome of patients with diabetic nephropathy after kidney transplantation.

During the period 1973-1983, 1,014 patients with end stage renal failure received a kidney graft at the Helsinki University Central Hospital. As a consequence of diabetic nephropathy, 163 of them (16%) developed renal failure. Ten diabetic (6%) and 72 non-diabetic (9%) patients received grafts from a living donor. One-year patient survival did not differ between diabetic and non-diabetic patients (76% and 79%, respectively). From the second post-transplant year onwards patient survival was worse in diabetic than in non-diabetic patients. The two groups did not differ with respect to graft survival. Sixty-two diabetic patients (38%) died during the follow-up period, with myocardial infarction as the most common cause of death (31%), followed by infection (15%) and cerebral stroke (13%). Seven myocardial infarctions out of 19 occurred within three months of transplantation. However, significantly more fatal and non-fatal myocardial infarctions were observed in post-transplant patients who had returned to dialysis therapy than in patients with a functioning kidney graft. Blindness did not influence the outcome of transplantation. Nor did the transplantation significantly affect the course of this diabetic complication. In conclusion, although the early success rate of kidney transplantation in our study population was acceptable, the later outcome was poor, mainly due to advanced disease-related complications.

Cardiovascular Diseases↗