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Biomedical subjects

G Kootstra

Publications and source records attributed to G Kootstra.

At least 127 records · Page 7Linked to original sources
PubMed1989

The beneficial effect of intermediate normothermic perfusion during cold storage of ischemically injured kidneys. A study of renal nucleotide homeostasis during hypothermia in the dog.

The effect of simple cold storage on ice with or without preceding warm ischemic injury on the energy metabolism and posttransplant viability of canine kidneys was examined in the present study. In addition, we investigated the possible beneficial effect of an intermediate normothermic perfusion half-way through the storage period on the preservation of ischemically injured kidneys. Thirty mongrel dogs were allocated to 5 experimental groups. In groups I and II kidneys were simply stored on ice for 24 and 48 hr, respectively. In groups III and IV kidneys were additionally subjected to 30 min warm ischemia before storage. In group 5 kidneys were treated as in group IV, but halfway through the storage period an intermediate normothermic ex-vivo perfusion was performed. The effect of these procedures on renal viability was tested by autologous reimplantation of the kidneys. During implantation the contralateral kidney was immediately removed. In group I all animals survived, whereas in group IV none of the animals survived. In groups II, III, and V, 2 of 6, 1 of 6, and 3 of 6 animals survived, respectively. The relationship, if any, between poststorage renal viability and the tissue levels of adenine nucleotides, guanine nucleotides, IMP, and purine degradation products was assessed by measuring the content of these metabolites in tissue specimen of the renal cortex, on which biopsies were done at various intervals during the experimental procedures. After an initial drop of about 30% in the content of adenine and guanine nucleotides and an increase in IMP, these values remained constant during 48 hr of cold storage. In contrast to kidneys stored for 24 hr, reimplantation of kidneys stored for 48 hr resulted in a significant decrease of adenine nucleotides following 60 min of in vivo reperfusion. Warm ischemia for 30 min prior to cold storage lead to lower initial nucleotide levels at the start of the storage period. During the first 24 hr nucleotide levels did not change, but a further decrease was observed during the following 24 hr of storage. Reimplantation after 24 hr of storage resulted in an additional decrease in the content of nucleotides. This poststorage decrease was absent after 48 hr of cold storage. Intermediate normothermic perfusion halfway through the storage for 48 hr significantly prevented the drop in the nucleotide content observed during the last 24 hr of storage in the corresponding control group. This nucleotide-sparing effect did not increase the level of nucleotides at the end of 60 min of reperfusion following reimplantation.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1989

Focal glomerulosclerosis in neonatal kidney grafts.

Two adult patients received both kidneys from neonatal donors. After grafting an accelerated growth of the kidneys was observed. Five weeks after transplantation the craniocaudal diameter had increased from 4 and 3.4 to 8.3 and 6.1 cm, respectively. Histological examination of the kidneys showed segmental glomerulosclerosis 24 and 3 months after grafting, respectively.

Adult↗
PubMed1989

Recurrence of nephrocalcinosis after renal transplantation in an adult patient with primary hyperoxaluria type I.

The medical history of a 42-year-old patient with primary hyperoxaluria type I is presented. Primary hyperoxaluria was suspected after renal transplantation, when oxalate deposits were found in a biopsy of the kidney graft. Diagnosis of type I hyperoxaluria was confirmed by the finding that significantly increased amounts of glycolic acid and oxalic acid were excreted. Treatment of the patient with 500 mg pyridoxine daily resulted in a decrease of the excretion of oxalate to normal values.

Adult↗
PubMed1989

Amplification of the nephrotoxic effect of cyclosporine by preexistent chronic histological lesions in the kidney.

In contrast to its importance in improving renal graft survival, nephrotoxicity is the most serious side effect of cyclosporine. Dosage reductions of CsA mitigate its nephrotoxic effect. However, CsA nephrotoxicity is still a problem in clinical transplantation. In this study the relationships among preexistent chronic histological lesions, donor age, and renal function after transplantation in 100 CsA treated renal allograft patients are described. Multivariate data analysis revealed a significant statistical effect of the presence of preexistent chronic histological lesions on nonimmediate function (-.42, less than 0.0001) that was relatively twice as large as the effects of cold ischemia time (-.21, less than 0.05). Also in predicting creatinine clearance at 1 and 3 months, preexisting chronic histological lesions had the most important effect (-.39, less than 0.0001; -.57, less than 0.0001, respectively), whereas the presence or absence of rejection episodes was less predictive (.24, less than 0.001; .20, less than 0.01, respectively). Preexistent chronic histological lesions had also significant effects in predicting conversion to azathioprine and prednisolone, because of CsA nephrotoxicity (-.42; less than 0.0001). The degree of CsA nephrotoxicity therefore varies according to the presence of preexistent chronic histological lesions. Because of the increase of these lesions with age, one has to be aware of an exaggerated CsA toxicity, especially in the older donor age group and in older patients treated with CsA for various reasons.

Age Factors↗
PubMed1988

Determination of warm ischemia time at donor nephrectomy.

To assess the warm ischemia time of kidneys with obscure donor histories we attempted to develop an index for the duration of ischemia by analysis of adenine nucleotides and their degradation products in cortical biopsies of canine kidneys. Two biopsy harvesting techniques were compared. The use of a laboratory technique (dentist's drill) resulted in higher concentrations of adenosine triphosphate (ATP) in normoxic tissue specimens as compared with a clinical method of harvesting biopsies (wedge biopsy). However the sum of adenine nucleotides (AN) (ATP, adenosine diphosphate [ADP], and adenosine monophosphate [AMP]) was not significantly different in both groups (P less than 0.05). Therefore, wedge biopsies were used to study the degradation of AN following 0, 30, 60, 90, and 120 min of ischemia. Adenine nucleotides and their degradation products were assayed by high-performance liquid chromatography. Concentrations of individual adenine nucleotides did not show a consistent correlation with warm ischemia time. However, as the sum of the AN and the sum of their degradation products (DP) decreased and increased, respectively, the balance between these metabolites offered a good correlation with duration of warm ischemia. The ratio of DP to AN was significantly different at each interval (P less than 0.05). To study the influence of temperature on the degradation process, ischemia was induced at 37 degrees C and 32 degrees C. Lowering of the temperature reduced the catabolic rate of the AN. The ratio of DP to AN was significantly different from corresponding values at 37 degrees C. In biopsies of nonischemic human donor kidneys, concentrations of adenine nucleotides and their degradation products were measured. Biopsies weighing less than 0.01% of total renal mass were large enough to meet analytical demands. The ratio of DP to AN in human kidney biopsies was in the same range as in the corresponding dog kidney biopsies. These findings demonstrate that the ratio of DP to AN, as determined from concentrations of purine metabolites in canine cortical wedge biopsies, is a sensitive and potentially useful index of warm ischemia time.

Adenine Nucleotides↗
PubMed1988

The cytokinetic behavior of donor hepatocytes after syngenic hepatocyte transplantation into the spleen.

The cytokinetic behavior of isolated hepatocytes transplanted into the spleen of syngenic normal Wistar rats was studied. Hepatocyte transplantation (HTX) was performed by the intrasplenic injection of 10(7) isolated hepatocytes. The proliferation index (PI) of intrasplenic donor hepatocytes was assessed by immunocytochemical visualization of DNA-synthesizing cells after pulse-labeling with bromodeoxyuridine (BrdU), a thymidine analogue. A method for determination of intrasplenic liver mass based on tissue glutamate dehydrogenase content was developed. The spontaneous PI of donor hepatocytes at 12 and at 20 weeks post-HTX amounted to around 3%. A significant increase of intrasplenic liver mass was demonstrated between the 12th and 20th week post-HTX (from 8.1 +/- 0.8% to 10.8 +/- 0.8% of spleen weight, P less than 0.05). After partial hepatectomy (PH) at 12 weeks post-HTX, the PI of liver cells in the spleen showed a transient increase up to about 10%, which rapidly declined to the "spontaneous" level of 3%. However, PH did not cause an additional increase in intrasplenic liver mass. This study shows that continuous mitotic activity of intrasplenic hepatocytes results in an actual increase of liver mass in spleen. Although a short-lived increase of proliferative activity of ectopically grafted hepatocytes was shown to occur after PH in the HTX-treated rat, this procedure did not result in an additional increase of intrasplenic liver tissue.

Animals↗
PubMed1988

Transplantation of isolated hepatocytes into the pancreas.

In previous research into hepatocyte transplantation (HTX) the spleen was the preferred acceptor organ for isolated donor hepatocytes. In this study the pancreas was tested as an acceptor organ for HTX. HTX into the pancreas or spleen was performed by injection of 10(7) isolated hepatocytes into the parenchyma of these organs. Intrapancreatic hepatocytes showed good viability 3 months after syngenic HTX as assessed by histological and immunocytochemical parameters. Definite proof of sustained metabolic activity of normal hepatocytes, 3 months after transplantation into the pancreas of congenitally jaundiced rats, was obtained by demonstration of bilirubin conjugates in bile of the recipients: 4.0% of total biliary bilirubin was conjugated. Intrasplenic HTX, however, was more effective and resulted in a conjugated fraction of 17.7% of total biliary bilirubin (p less than 0.001). Reduction of total plasma bilirubin was significant with both methods, but more pronounced in intra-splenic HTX. Bile drainage from the hepatocellular transplant via the pancreatic excretory system into the gut was not observed: conjugated bilirubins were not found in pancreatic juice of HTX-treated jaundiced rats. Intrapancreatic HTX did not adversely affect the host rat; evidence of pancreatitis or diabetes was not found. It is concluded that the pancreas is a suitable acceptor organ for HTX. However, intrapancreatic HTX appears to be less effective than intrasplenic HTX in the treatment of enzyme deficiency disease.

Animals↗