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Biomedical subjects

G Kootstra

Publications and source records attributed to G Kootstra.

At least 163 records · Page 9Linked to original sources
PubMed1987

A new variant for whole pancreas grafting.

A new variant for whole pancreas grafting is described in which a segment of the duodenum and the spleen is included in the graft. The graft is placed extraperitoneally as in kidney transplantation. The exocrine drainage is with side-to-side anastomosis between duodenum and bladder. The spleen is irradiated to prevent the occurrence of GVHD, as is reported in splenic transplantation.

Adult↗
PubMed1987

Pancreatic transplantation in patients with type-I diabetes: the experience in Maastricht with a new model.

A successful pancreatic transplant together with a kidney graft makes type-I diabetic patients with end-stage diabetic nephropathy independent from insulin and dialysis. Several surgical techniques for the pancreatic graft are employed. Major problems are thrombosis of the graft and the handling of the exocrine secretion of the pancreas. A transplant model is presented that reduces the risk of thrombosis by including the spleen in the graft. The exocrine secretion is handled by transplanting a segment of duodenum with the graft and by connecting this segment to the recipient's bladder. Experience has been gained in four patients. All are insulin-independent. Severe complications have not been observed, which makes this model suitable for further assessment of the effect of pancreatic transplantation on the course of type-I diabetic patients.

Adult↗
PubMed1986

Analysis of cytotoxic T lymphocyte response in rejecting allografted canine kidneys.

The involvement of cytotoxic T lymphocytes (CTL) in the rejection process of allografted canine kidneys was studied. The frequency of donor-specific (precursor) CTL was determined with a sensitive limiting dilution assay. Longitudinal sampling of peripheral blood and kidney aspiration biopsies were used to obtain information on the CTL response toward the graft. An accurate analysis of CTL kinetics in both kidney and peripheral blood of allografted dogs appeared to be technically possible. During the first days after transplantation precursor CTL (CTLp) frequencies decreased in both blood and kidney. A minimum CTLp frequency of 5-15% of the pretransplant value was reached in the peripheral blood at day 4 after transplantation. The cause of this decrease, which was observed in all 5 allografted dogs is discussed. CTLp frequencies increased after day 4 and showed an exponential rise in the kidney before serum creatinine increased due to loss of kidney function caused by rejection. The data obtained with the quantitative study of CTL show that rejection of a canine kidney allograft is accompanied by a rise in CTL numbers in the kidney. The methodology developed permits extensive functional analysis of cellular processes in allografted organs.

Animals↗
PubMed1986

Local treatment of renal allografts, a promising way to reduce the dosage of immunosuppressive drugs. Comparison of various ways of administering prednisolone.

A method is described for continuous administration of immunosuppressive drugs directly into rat renal allografts. The drug is given via a catheter, introduced into the suprarenal or testicular artery of the transplanted kidney. The cannula is connected to an implantable osmotic minipump that delivers an immunosuppressive drug with continuous flow for 13 days. It is demonstrated that the technique as such has no detrimental or enhancing effects on renal allograft survival. Depending upon the pharmacokinetic properties of the drug administered, this technique allows a more or less selective treatment of renal allograft rejection. The method was used to test the effect of intrarenal administration of prednisolone on renal allograft survival. Intrarenal administration of this drug appeared to be superior to any other way of administration tested. A low dose of 4 mg/kg body weight per day given by continuous intrarenal infusion results in significant prolongation of graft survival, whereas continuous systemic administration of this dose is not effective. To induce prolongation of graft survival by i.p. administration the prednisolone dose had at least to be doubled. The results prove that during graft rejection local events within the graft are vulnerable to prednisolone. It is concluded that local treatment of allograft rejection is possible and that this approach represents a potentially important way to manipulate the immune response.

Animals↗
PubMed1986

Hepatocyte transplantation for enzyme deficiency disease in congenic rats.

Long-term effects of hepatocyte transplantation (HTX) in the treatment of enzyme deficiency disease were studied. Congenic enzyme-deficient (R/APfd-j/j) and non-enzyme-deficient (R/APfd) rats were used as recipients and donors, respectively. The R/APfd-j/j rat strain is congenitally deficient of bilirubin uridyldiphosphate (UDP)-glucuronyl transferase. R/APfd-j/j rats underwent HTX by intrasplenic injection of 10(7) isolated R/APfd hepatocytes (group 1A). Another group of R/APfd-j/j rats was treated similarly, but underwent splenectomy after 11 weeks (group 1B). Controls consisted of R/APfd-j/j rats grafted with 10(7) R/APfd-j/j hepatocytes (group 2), and R/APfd-j/j rats that underwent a sham operation (group 3). Total plasma bilirubin (TB) levels were significantly reduced in groups 1A and 1B during the experiment (both P less than 0.01). In the control groups TB reduction was not observed. Bile analyses at 30 weeks after HTX showed that in group 1A 13.7 +/- 2.7% of total biliary bilirubin was conjugated. In group 1B a significantly lower fraction was conjugated: 6.6 +/- 1.1% (P less than 0.05). Conjugated bilirubin was not found in bile of groups 2 and 3. Histology showed survival of hepatocytes in all spleens of rats of groups 1A, 1B and 2. It is concluded that congenic hepatocytes from R/APfd donors are not rejected after transplantation into the R/APfd-j/j rat, and maintain long-term function. Splenectomy does not abolish, but does reduce, the therapeutic effect significantly, indicating that part of the transplanted hepatocytes maintains function in the enzyme-deficient host liver. The congenic R/APfd-j/j and R/APfd rat strains represent a new animal model for research in metabolic deficiency disease.

Animals↗
PubMed1986

Prevention and treatment of supraventricular tachycardia shortly after coronary artery bypass grafting: a randomized open trial.

Supraventricular arrhythmias continue to complicate the postoperative course of patients following coronary artery bypass grafting. In a randomized, open, controlled trial we assessed the value of two different beta-blocking agents in the prevention and treatment of these arrhythmias. Of 151 consecutive patients undergoing coronary artery surgery, 39 were treated with metoprolol and 41 were treated with sotalol (a beta blocker with class III antiarrhythmic properties). Fifty patients served as a control group and received no prophylactic therapy. Twenty-one patients were eliminated from the study for various reasons, making a final total of 130 in the study group. In the metoprolol group 15.3% of patients developed supraventricular tachycardia SVT after coronary artery surgery, which was significantly less (p less than 0.05) than the incidence observed in the control group. However, in the group of patients receiving sotalol, 2.4% developed SVT (p less than 0.01 compared with the control group). Of 18 patients in the control group who developed SVT after randomization, 10 received sotalol and 4 metoprolol to terminate the arrhythmia. The mean time of termination of SVT after drug administration was 2.4 +/- 1.8 hours for treatment with sotalol and 13.6 +/- 9.8 hours for treatment with metoprolol. We conclude that sotalol significantly reduces the incidence of supraventricular tachycardia in the early period after coronary artery bypass surgery.

Adrenergic beta-Antagonists↗
PubMed1986

Use of horseshoe kidneys for transplantation.

Report of a case in which a horseshoe kidney was divided and transplanted into two recipients. The literature on transplantation of horseshoe kidneys is reviewed. This renal anomaly is not a contra-indication to its use for transplantation.

Adolescent↗
PubMed1985

Treatment of enzyme deficiency by hepatocyte transplantation in rats.

The inbred, homozygous Gunn rat exhibits unconjugated hyperbilirubinemia due to a hereditary absolute deficiency of bilirubin UDP-glucuronyltransferase activity. The mechanism of action of hepatocyte transplantation (HTX) in the treatment of enzyme deficiency has been investigated in this study. Gunn rats underwent HTX by the injection of isolated hepatocytes from a nondeficient donor rat (Wistar) into the spleen. A transient, statistically significant decrease in total plasma bilirubin (TB) levels was observed. Gunn rats receiving Gunn hepatocytes did not show such a decrease. Histological examination 2-3 months post-HTX of the recipient spleens showed the absence of grafted hepatocytes in the first group and graft survival in the second. Bile specimens from sublethal irradiated Gunn rats, collected 6 days after HTX with viable Wistar hepatocytes, all contained bilirubin mono- and diglucuronides. Control groups consisting of Gunn rats receiving nonviable Wistar hepatocytes or Gunn hepatocytes, and sham-operated Gunn rats did not excrete bilirubin glucuronides in bile. It was also demonstrated that bilirubin UDP-glucuronyltransferase activity, which appeared in Gunn rats after HTX with Wistar hepatocytes, was only transient. It is concluded that the decrease of TB in the Gunn rat after HTX with nondeficient hepatocytes is explained by the appearance of the enzyme, which was absent in the recipient animal. Viable, nondeficient hepatocytes are required for the elicited bilirubin conjugation. Rejection of the transplanted hepatocytes abolishes this effect.

Animals↗
PubMed1985

Cell-mediated cytotoxicity patterns of cloned cytotoxic T lymphocytes. Cytotoxicity directed against canine lymphoblasts, monocytes, and endothelial cells.

Knowledge of the antigens recognized during allograft rejection is still incomplete. Cloned cytotoxic T lymphocytes were used to study the distribution of target determinants in the dog. CTL clones were obtained with a limiting dilution technique from effector cells generated in mixed lymphocyte culture. The clones have been tested for cell-mediated cytotoxicity against PHA-stimulated lymphoblasts, monocytes, and arterial and venous endothelial cells. A limited number of patterns of lysis of one, or more than one, of the four different target cells was observed. The nature of the possible target determinants recognized by these CTL-clones is discussed.

Animals↗
PubMed1985

Complete suppression of skin allograft rejection in rats treated with continuous infusion of 2'deoxycoformycin.

Congenital deficiency of the enzyme adenosine deaminase (ADA) results in severe combined immunodeficiency. 2'deoxycoformycin (2'dcf) is a tightly binding inhibitor of ADA, and the drug makes it possible to mimic a state of ADA deficiency. In this study we tested the immunosuppressive effect of 2'dcf in a rat skin transplantation model. Rats treated with continuous infusion of 2'dcf at doses of 0.3 mg/kg, 0.5 mg/kg and 0.7 mg/kg body wt/day showed significant prolongation of graft survival. 2'dcf given by bolus injections did not prolong graft survival. In rats treated with continuous infusion of 2'dcf at a dose of 0.7 mg/kg body wt/day mean graft survival time (MST) after withdrawal of treatment was equal to MST in untreated animals, suggesting that during 2'dcf treatment allograft rejection was completely suppressed. In vitro, lymphocytes isolated from animals treated with continuous infusion of 2'dcf showed marked suppression of mitogen response. The 2'dcf preferentially effects lymphocytes, but neutrophils seem resistant to the effect of the drug. The lymphocytotoxic effect of the drug is extreme; during therapy splenic weight decreased by almost 50% and the differential lymphocyte count in blood decreased from 85% to 17%. Immunofluorescence studies showed that, within the spleen, the amount of T cells and B cells decreased markedly. Both T cell subsets were affected--OX8+ cells (suppressor/cytotoxic T cells) and W3/25+ (helper T cells). However OX8+ cells were more resistant to the drug than W3/25+ cells. Skin-grafted rats treated with 2'dcf showed a strong decrease in the W3/25: OX8 ratio. In contrast, untreated rats showed a slight increase in the ratio after skin transplantation. It is concluded that 2'dcf is a strong immunosuppressive drug in rats if given by continuous infusion.

Adenosine Deaminase↗
PubMed1984

Canine IL-2: characterization and optimal conditions for production.

The culture requirements for the production of canine I1-2 are reported. Several parameters have been tested, such as concentration of lectin, length of culture period and presence of the additives serum, polyethylene glycol (PEG) and phorbol myristic acetate (PMA). Optimal results have been obtained by stimulation of peripheral blood leukocytes with the lectin PHA (8 micrograms/ml) for 48 h. Techniques for the production of I1-2 containing supernatant free of PHA have been evaluated. Gel filtration chromatography of culture supernatant revealed that canine I1-2 has a molecular weight (m.w.) of approximately 30,000 daltons, similar to the m.w. of I1-2 produced by murine T cells.

Animals↗
PubMed1984

Surgical treatment of organic hyperinsulinism in infancy. Surgical procedure in the absence of a demonstrable insulinoma and a peroperative diagnosis of nesidioblastosis.

This study consists of a review of 5 children operated on for organic hyperinsulinism. The diagnosis could be established by demonstrating the repeated presence of elevated serum insulin levels during hypoglycaemia and/or a rapid glucose disappearance. From our experience with this series and by a review of the literature the following data are relevant to the management of these children. Because of the risk of brain damage there is no justification for prolonged diagnostic and therapeutic trials. Surgical exploration of the pancreas is indicated without delay. When during exploration no localised lesion can be found, the diagnosis "nesidioblastosis" can be established by frozen section evaluation. Whether a diagnosis of nesidioblastosis has been established or not, a 90-95% subtotal pancreatectomy has to be performed subsequently, because this operation will cure most of the children with organic hyperinsulinism, has negligible complications and preserves normal exocrine and endocrine pancreatic function. A near-total pancreatectomy has to be performed without delay in patients with recurrent hypoglycaemia caused by persisting organic hyperinsulinism after the first operation.

Adenoma, Islet Cell↗