Search PubMed⌕ Search

Biomedical subjects

G Kootstra

Publications and source records attributed to G Kootstra.

At least 91 records · Page 5Linked to original sources

Survival of arteriovenous fistulas and shunts for haemodialysis.

OBJECTIVE: To formulate a standard for assessing functional patency of vascular access and to present long-term results of vascular access in a group undergoing dialysis, in particular the effects of percutaneous transluminal angioplasty (PTA). DESIGN: Retrospective study 1971-1980, prospective study 1980-1991. SETTING: A unit for haemodialysis in a regional hospital, The Netherlands. SUBJECTS: All 259 patients treated from 1971 to 1991 in a programme for chronic haemodialysis. INTERVENTIONS: All interventions, surgical and radiological, needed to maintain vascular access. MAIN OUTCOME MEASURES: Intervention free periods, patency of access, life expectancy of access, and early failure rate (within 4 days). Patency of access before and after PTA. RESULTS: A total of 1179 interventions were made. 407 Arteriovenous (A-V) fistulas and shunts were constructed, and there were 519 surgical reoperations and 253 PTAs. The secondary cumulative patency rate for the autogenous distal A-V fistulas (Cimino) was 79% at one year, 68% at two years, and 59% at three years. Routine use of PTA from 1986 onwards resulted in a rise in secondary cumulative patency for Cimino A-V fistulas after two years from 65% to 80% (p > 0.05). CONCLUSIONS: To describe and assess vascular access the patency rate alone is not sufficient; intervention free periods and life expectancy must also be given. Routine use of PTA with the Cimino A-V fistula resulted in an appreciable but not significant increase patency at two years.

Adolescent↗

University of Wisconsin solution is superior to histidine tryptophan ketoglutarate for preservation of ischemically damaged kidneys.

The current shortage of transplantable organs has renewed interest in kidneys obtained from non-heart-beating donors. Kidneys from these donors have suffered warm ischemia (WI). The effectiveness of two preservation solutions, i.e., the University of Wisconsin (UW) and the histidine tryptophan ketoglutarate (HTK) solutions, for preservation of kidneys that have been subjected to WI was tested in dogs. The left kidney was autotransplanted after 30 min of WI, and subsequent 24-hr cold storage (CS) in either UW (n = 6) or HTK (n = 6), with immediate contralateral nephrectomy. Surgical biopsies from the cortex were taken before WI, after 30 min of WI, after 24 hr of CS, and after 1 hr of reperfusion for electron microscopy and for analysis of energy metabolites. At 2 weeks after transplantation in the UW group, 4 out of 6 and, in the HTK group, 1 out of 6 dogs survived. As from day 2, serum creatinine was lower in the UW group as compared with the HTK group (P < 0.05). After 24 hr of CS, in the HTK group the luminal membranes of proximal tubular cells were partly denuded of microvilli. Moreover, the tubular lumen was filled with blebs and debris. In the UW group, the brush borders remained intact, although microvilli were swollen. Energy metabolites were analyzed with HPLC. Thirty minutes of WI resulted in a +/- 45% reduction of total adenine nucleotide (TAN) content. During CS, TAN levels further decreased in both groups; however, after 24 hr of CS, the levels of adenosine, inosine, hypoxanthine, and xanthine were significantly higher in the UW group as compared with the HTK group (P < 0.05, P < 0.01, P < 0.01, P < 0.01). At 1 hr of reperfusion, TAN levels were higher in the UW group as compared with the HTK group (4.66 +/- 0.16 vs. 4.02 +/- 0.28, P < 0.05). Our results show that UW is a superior solution compared with HTK in the preservation of ischemically damaged kidneys, demonstrating better survival, better recovery of kidney function, better protection against ischemia-induced ultrastructural damage, and better preservation of energy metabolism indicated by (a faster) regeneration of TAN levels after reperfusion.

Adenine Nucleotides↗

A simple technique to harvest two kidneys from one donor rat for transplantation.

Kidney transplantation in rats is a widely used and well established model in transplantation immunology and preservation research. With the conventional method, only one kidney is harvested from the donor rat. We developed a technique to harvest two kidneys separately from one donor, subsequently both kidneys were successfully implanted into two recipient rats. This technique which leads to a reduction of the number of experimental animals used is discussed in detail.

Animals↗

Nonheart-beating donors: the Maastricht experience.

The growing gap between the number of organs available for transplantation and patients on waiting lists demands additional donor sources. Nonheart-beating (NHB)-donor programs are known to increase the number of kidneys available. The group of potential NHB donors is very diverse and therefore 4 categories have been identified. At the University Hospital Maastricht, a NHB-donor program was implemented in 1980 to harvest kidneys after an in situ perfusion technique. In order to evaluate the function of kidney grafts from NHB donors, a retrospective multicenter study on the NHB-donor kidneys transplanted until 1992 was performed, using a control group of kidneys from heart-beating (HB) donors. The short-term results showed more delayed function (DF) in the NHB-donor group accompanied by higher serum creatinine levels at one-month posttransplant. The long-term outcome, however, was equal in both groups showing similar graft and patient survival rates up to 5 years. Apart from the type of donor, HB or NHB, only the number of HLA-DR mismatches could be identified as a potential risk factor for delayed graft function. NHB donors contribute considerably to reducing the gap between offer and demand in kidney transplantation and transplant centers should include NHB donors in their procurement programs. Meanwhile, efforts should be made to improve the short-term posttransplant graft function. Together with reducing DF, searching for valuable tools in viability assessment should also be an objective. Past viability tests never found broad clinical use but might be important in the optimal and safe usage of the potential NHB donor pool.

Adolescent↗

In situ preservation of kidneys from non-heart-beating donors--a proposal for a standardized protocol.

The growing success in renal transplantation has resulted in an increase in the need for donor organs. Procurement of kidneys from heart-beating (HB) donors is unlikely ever to meet this demand. Non-heart-beating (NHB) donors offer a yet untapped source of renal grafts. Cadaver kidneys from patients who have sustained cardiac standstill are often considered unsuitable for transplantation due to prolonged warm ischemia time. Using an emergency in situ perfusion technique it is possible to limit warm ischemic damage and to salvage these kidneys for transplantation. The procedure requires prompt action and cooperation of emergency service personnel. This report presents a protocol for the emergency in situ preservation procedure that can be practiced in most hospitals. At the University Hospital of Maastricht, The Netherlands, implementation of this procedure resulted in 20% more kidneys available for transplantation. Although NHB donor kidneys showed a higher rate of delayed function compared with a matched HB donor kidney population, there was no significant difference in long-term graft survival between the two groups.

Brain Death↗

The role of the spleen in pancreas transplantation.

Early graft thrombosis and rejection of the graft are the two major causes of graft failure in pancreas transplantation. Inclusion of the spleen in the pancreatic graft has been purported as a possible solution to both complications, but severe graft-versus-host disease led to abolishment of this procedure. By irradiating the donor spleen ex vivo during cold storage, we successfully prevented graft-versus-host disease, allowing us to evaluate the advantages of clinical pancreaticosplenic transplantation. This study reports our experience with 12 pancreaticosplenic transplantations. Using Doppler flow measurements, we have been able to examine the hemodynamic advantages. Our results confirm the purported benefit. Vascular resistance indices in the pancreatic graft are significantly lower when the donor spleen is included. This, however, did not lower the incidence of thrombosis (2 out of 12 cases) in our study. Serial radionuclide studies with 99mTc-hexamethyl propylene amine oxime were performed for further evaluation of graft perfusion. With time the spleen uptake diminishes, compatible with atrophy of the organ. This was confirmed histologically. No indication of an immunologic advantage of transplanting the pancreas together with the spleen was found. All patients went through severe rejection crises. A transient reduction in platelet count (55-88%, mean 71%) of preoperative values was observed. This platelet drop is not seen in patients with a pancreas without spleen transplantation. We conclude that in pancreas transplantation, inclusion of the irradiated spleen has no obvious advantages for early graft thrombosis and rejection of the graft.

Adult↗

Toxicology of FK506 in the cynomolgus monkey: a clinical, biochemical, and histopathological study.

We investigated clinical, biochemical, and histopathological parameters in FK506-treated cynomolgus monkeys. Eight monkeys given oral FK506, 1 (n = 4) or 10 (n = 4) mg/kg daily, survived the 90 days of treatment apparently in good health and without significant changes in biochemical and histopathological parameters, as did 2 control monkeys except one monkey on 10 mg/kg/day FK506 orally, who was found to have a malignant lymphoma. In contrast, monkeys given intramuscular FK506 1 mg/kg daily (n = 4) had to be sacrificed at day 20, 25, 32, and 47 because of severe illness. They showed abnormal biochemical parameters (increased serum urea and aspartate aminotransferase activity) and major histopathological changes in the kidney (mesangial cell proliferation and acute tubular necrosis), pancreas (depletion of beta cells), liver (steatosis), and heart (cardiomyopathy). Intramuscular administration of 1 mg/kg daily resulted in serum levels ranging from 10 to 15 ng/ml, while oral administration at a dose of 1 or 10 mg/kg daily resulted in equal or even higher serum levels (range 2-70 ng/ml). Thus, the height of the serum trough level of FK506 using the enzyme immunoassay is not related to the toxicity of FK506 in cynomolgus monkeys.

Administration, Oral↗

The impact of ischemic lesions in the donor kidney, donor age, recipient age and HLA (A, B, C, DR, DQ) matching on clinical course after kidney grafting.

It is generally accepted that HLA matching improves graft survival. However, there is no consensus on whether this improvement is reflected on daily clinical course. Clinical course after renal transplantation depends on many factors, such as donor age, recipient age, ischemic score in the kidney, and HLA matching. The relative contribution of these factors is unknown. Because management of the recipients in the various centers differs considerably, only a single centre study would reveal the relative contribution of all these factors. Therefore, in our centre we studied the influence of these parameters on the clinical course after renal allografting.

Age Factors↗

Perfusion imaging of pancreas allografts using technetium-99m hexamethyl propylene amine oxime.

The vascular integrity and major changes in perfusion can be determined by visual interpretation of radionuclide flow studies. We studied the potential of a new radiopharmaceutical technetium-99m hexamethyl propylene amine oxime (99mTc-HMPAO) in the particular setting of pancreas transplantation. Perfusion was measured by perfusion indices (PI). Changes in graft perfusion were estimated by three independent observers. A predefined scale from 0 to 4 was used, with 0 representing no visualisation of the graft and 4 denoting sharp countour delineation and distinct demarcation from the background. In order to investigate the relation between perfusion of the pancreas graft and its exocrine function, we measured the amylase excretion rate (AER) in the urine, expressed in units per hour. It is concluded that 99mTc-HMPAO is a suitable radiopharmaceutical for pancreas allograft imaging. For the assessment of the vascular integrity in the direct postoperative period, the scintigram is very reliable. Although a correlation between exocrine function of the graft and the perfusion score was not established, it is possible to make a clear sorting of AER measurements into different groups.

Amylases↗

Reperfusion injury of pancreas allografts: relation to islet cell function.

It is unknown to what extent preservation and/or reperfusion may damage islet cells in pancreas allografts. In this study, the release of insulin after reperfusion was used as a marker of injury to the islet cell and compared with the best insulin secretory response (ISR) after glucagon stimulation over a period of 100 days after pancreas transplantation.

Adult↗

The effect of FK506 treatment on pancreaticoduodenal allotransplantation in the primate.

The effect of FK506 monotherapy on pancreaticoduodenal allotransplantation was studied in a primate model. The recipients were made diabetic by total pancreatectomy, thus glycemic control depended on the graft. In control animals hyperglycemia occurred after 14 +/- 3 days and the animals died after 36 +/- 15 days. For FK506-treated animals, the time until development of hyperglycemia was 60 +/- 12 days (P less than 0.05). The animals were then sacrificed by day 90 (P less than 0.05). All three control animals lost their graft function because of severe rejection, as verified by postmortem examination. Only one of the five treated animals showed evidence of a moderate-to-severe rejection at 90 days, one animal having a mild rejection as judged by the histological findings. The drug was clinically well tolerated in all except one animal that became apathetic and refused to eat. Hyperglycemia and an elevated serum creatinine level, which were probably related to the FK506 treatment, occurred in one animal each. Both of these side-effects were reversed by reducing the dose. Thus the use of FK506 permits successful single pancreatic transplantation in primates.

Amylases↗

FK506-induced impairment of glucose metabolism in the primate--studies in pancreatic transplant recipients and in nontransplanted animals.

The effect of FK506 on glucose metabolism was studied in five cynomolgus monkeys after pancreatic transplantation and in 10 nontransplanted cynomolgus monkeys. We have clearly demonstrated that FK506 can induce hyperglycemia in these animals. In the orally treated nontransplanted animals the hyperglycemia was usually very mild (4.5-6.0 mmol/L). In one of the five transplanted animals, hyperglycemia was induced by the FK506 treatment, since histological signs of rejection were absent and since plasma glucose levels normalized on dose reduction. The glucose disappearance rates, as indicated by the K-values, decreased from a mean of 3.0 +/- 0.5%/min before FK506 treatment to 2.4 +/- 0.6%/min at one month and 1.5 +/- 0.4%/min at three months in the nontransplanted animals. In the transplant group, the K values decreased significantly from 4.2 +/- 0.6%/min in the donor animals to 1.4 +/- 0.4%/min at day 10 posttransplantation (P < 0.02). At one and three months postoperatively, the mean K-values were 1.4 +/- 0.2%/min and 1.2 +/- 0.6%/min, respectively. We conclude that FK506 is diabetogenic in the cynomolgus monkey. This side effect, however, was found to be reversible on dose reduction.

Animals↗