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M J Slooff

Publications and source records attributed to M J Slooff.

At least 19 recordsLinked to original sources
PubMed2004

['New pathways to organ donation'; a recommendation of the Dutch Health Council].

Despite recent efforts at improvement, the current status of postmortem organ donation in the Netherlands is a reason for serious concern. The waiting lists for all organ transplantations are increasing in length. The Dutch Health Council was asked by the Minister of Health to report on any available alternative sources of donor organs, focusing especially on donation from living donors and postmortem donors in whom the heart is no longer beating. Kidney donation by living relatives is a well-known procedure that has been performed since 1950. Since HLA-matching is now less important due to new immunosuppressive regimens, transplants from unrelated living volunteers are also possible with good results. Live donation from emotionally involved persons should be encouraged. In case of ABO incompatibility, donors could be exchanged via the organ exchange institution. Live donation of liver segments by an adult to benefit a child recipient is justified. In case of an adult recipient this should be performed only under exceptional circumstances. Live donation of lung lobes and segments of intestine is still in a developmental phase. Postmortem donation of kidneys and livers from donors in whom the heart is no longer beating should also be encouraged. Donation of the lungs and pancreas from these donors is still an experimental procedure.

ABO Blood-Group System↗
PubMed2001

Rapid decreases in donor-specific cytotoxic T lymphocyte precursor frequencies and graft outcome after liver and lung transplantation.

BACKGROUND: A decrease in donor-specific T cell precursor frequencies as seen late, one or more years, after transplantation is assumed to reflect transplantation tolerance, a condition important for long term acceptance of the allograft. However, such late decreases also occur in recipients that developed chronic transplant dysfunction questioning its relevance in transplantation tolerance. We investigated whether early, i.e., the first 6 months, decreases in donor-specific T cell precursor frequencies reflect transplantation tolerance and predict graft outcome after liver and lung transplantation. METHODS: Donor and third party specific cytotoxic (CTLp) and helper T lymphocyte precursor (HTLp) frequencies were analyzed in pretransplant and 1 (or 2) and 6-month blood samples taken from liver and lung recipients and were correlated with graft outcome. RESULTS: In liver allograft recipients with good graft function (n=7), mean donor-specific CTLp frequencies decreased as early as 1 month after transplantation and remained low thereafter. In contrast, mean CTLp frequencies did not decrease in liver allograft recipients with chronic transplant dysfunction (n=6). In lung allograft recipients, donor-specific CTLp frequencies remained relatively high and frequencies were not different between recipients without (n=6) or with (n=6) chronic transplant dysfunction. Donor-specific HTLp frequencies did not change significantly after liver or lung transplantation and did not differ between recipients without or with chronic transplant dysfunction. CONCLUSIONS: An early decrease in donor-specific CTLp correlates with good graft outcome after liver transplantation. Such rapid decreases in alloreactivity do not occur after lung transplantation illustrating the unique capacity of liver allografts to induce transplantation tolerance.

Humans↗
PubMed2001

[Liver transplantation from a living donor: necessity or an alternative?].

Liver transplantations using a part of the liver from a living donor are already being performed around the world. The main arguments for performing such transplantations are the shortage of brain-dead donors and the consequently high mortality rate of patients on the waiting list for a liver transplantation. The disadvantages of this option are the mortality and morbidity risk for the living donor. The shortage of brain-dead donors could also be resolved by the implementation of special techniques such as split-liver and domino-liver transplantations or by using compromised and non-heart-beating donors. Furthermore, measures should be taken to reduce the shortage of brain-dead donors in the Netherlands. If such actions do not lead to an increase in the number of brain-dead donors and a willingness to restrict the indications for transplantation is not forthcoming then donation for liver transplantation by living donors is inevitable. Such a program should satisfy certain conditions and have the requisite medical-ethical and public support.

Health Policy↗
PubMed2001

Reduced transfusion requirements by recombinant factor VIIa in orthotopic liver transplantation: a pilot study.

BACKGROUND: Large transfusion requirements, i.e., excessive blood loss, during orthotopic liver transplantation (OLT) are correlated with increased morbidity and mortality. Recombinant factor VIIa (rF-VIIa) has been shown to improve hemostasis in a variety of conditions, but has never been studied in liver transplantation. METHODS: We performed a single-center, open-label, pilot study in adult patients undergoing OLT for cirrhosis Child-Pugh B or C, to assess efficacy and safety of rFVIIa. rFVIIa (80 microg/kg) was administered at the start of the operation, to be repeated according to predefined criteria. Packed red blood cells (RBC), fresh-frozen plasma, and platelet concentrates were administered according to predefined criteria. Perioperative transfusion requirements in study patients were compared with matched controls. RESULTS: Six patients were enrolled in the study. All received a single dose of rFVIIa. Transfusion requirements (given as median, with range in parentheses) were lower in the study group than in matched controls: 1.5 (0-5) vs. 7 (2-18) units of allogeneic RBC (P=0.006), 0 (0-2) vs. 3.5 (0-23) units of autologous RBC (P=0.043), total amount of RBC 3 (0-5) vs. 9 (4-40) units (P=0.002). Transfused fresh-frozen plasma was 1 (0-7) vs. 8 (2-35) units (P=0.011). Blood loss was 3.5 L (1.4-5.3) vs. 9.8 L (3.7-35.0) (P=0.004). One study patient developed a hepatic artery thrombosis at day 1 postoperatively. CONCLUSIONS: A single dose of 80 microg/kg rFVIIa significantly reduced transfusion requirements during OLT. Further study is needed to establish the optimally effective and safe dose of rFVIIa in orthotopic liver transplantation.

Adult↗
PubMed2001

Retransplantation of the liver in children.

BACKGROUND: Because of the poor outcome of hepatic retransplantation, it is still debated whether this procedure should be performed in an era of donor organ scarcity. The aim of this study was to analyze outcome of hepatic retransplantation in children, to identify risk factors influencing this outcome, and to assess morbidity and causes of death. METHODS: A series of 97 children after a single transplantation and 34 children with one retransplantation was analyzed. RESULTS: The 1-, 3-, and 5-year survival of children with a retransplantation was 70, 63, and 52%, respectively, compared with 85, 82, and 78%, respectively, for children after a single transplantation (P=0.009). Survival of children with a retransplantation within 1 month after primary transplantation was worse (P=0.007) and survival of children with a late retransplantation was comparable (P=0.66) with single transplantation. In early retransplantations, the Child-Pugh score was higher, donors were older and weighed more, and more technical variant liver grafts were used compared with single transplantations. Biliary atresia and a high Child-Pugh score were associated with decreased patient survival after retransplantation. Sepsis was the most important complication and cause of death after retransplantation. CONCLUSIONS: Retransplantation is a significant event after pediatric liver transplantation. Outcome after hepatic retransplantation in children is inferior compared with single transplantation. This difference is explained by low survival after early retransplantation and can be explained by the poor clinical condition of the children at time of retransplantation, especially in children with biliary atresia, and by the predominant use of technical variant liver grafts in retransplantations.

Child↗
PubMed2001

Serum response of hepatocyte growth factor, insulin-like growth factor-I, interleukin-6, and acute phase proteins in patients with colorectal liver metastases treated with partial hepatectomy or cryosurgery.

BACKGROUND/AIMS: The aim of the study was to compare the serum response of regeneration factors and acute phase proteins in patients treated with partial hepatectomy or cryosurgery. METHODS: The responses of serum hepatocyte growth factor (HGF), insulin-like growth factor-I (IGF-I) (free and total), interleukin-6 (IL-6) and the acute phase proteins, C-reactive protein (CRP) and serum amyloid A (SAA) were examined in patients with colorectal liver metastases treated with partial hepatectomy (n = 14) or cryosurgery (n = 10). RESULTS: In both groups, IL-6 peak levels at the end of the operation were followed by peak levels at day 1 for HGF and CRP. SAA peak levels occurred on day 1 (hepatectomy group) and on day 4 (cryo group). The total HGF, IGF-I, and IL-6 responses were comparable in both groups. CRP and SAA responses were higher in the patients treated with cryosurgery than in patients after hepatectomy. Free IGF-I trough levels were lower in partial hepatectomy patients than in cryosurgery patients. CONCLUSIONS: In patients with colorectal liver metastases the responses of the regenerating factors HGF, IGF-I, and IL-6 are comparable to those in patients treated with partial hepatectomy. Upregulation of acute phase protein production is higher in patients after cryosurgery than in patients after partial hepatectomy.

Acute-Phase Proteins↗
PubMed2001

Increased cancer risk after liver transplantation: a population-based study.

BACKGROUND/AIMS: Development of de novo malignancies emerges as a serious long term complication after liver transplantation. METHODS: We reviewed the medical records of 174 adult one-year survivors for de novo malignancies. The observed cancer rates were compared with the expected cancer rates in the Dutch population. RESULTS: Twenty-one of the 174 patients developed 23 malignancies (12%). Skin and lip cancer accounted for 12 of the 23 malignancies (52%). Only one patient had a B-cell lymphoma. The cumulative risk for de novo malignancy was 6, 20, and 55% at 5, 10, and 15 years after transplantation, respectively. The overall relative risk (RR) as compared with the general population was 4.3 (95% confidence interval 2.4-7.1). Significantly increased RRs were observed for non-melanoma skin cancer (RR 70.0), non-skin solid cancer (RR 2.7), renal cell cancer (RR 30.0), and colon cancer (RR 12.5). Multivariate analysis showed that an age > 40 years and pretransplant use of immunosuppression were significant risk factors. CONCLUSIONS: An increased risk of cancer exists after liver transplantation, for both for skin/lip cancer, and other solid tumors. Older age and the use of immunosuppression are risk factors.

Adult↗
PubMed2001

Rat liver slices as a tool to study LPS-induced inflammatory response in the liver.

BACKGROUND/AIMS: Inflammation in the liver is a complex interaction between parenchymal and non-parenchymal cells, and therefore can not be studied in vitro in pure cultures of these cells. METHODS: We investigated whether Kupffer cells in the liver slice are still responsive to an inflammatory stimulus of lipopolysaccharide (LPS), and evoke an inflammatory response in the hepatocytes. RESULTS: TNFalpha, IL-1beta and IL-10 were significantly elevated in culture medium of LPS-stimulated rat liver slices. Nitric oxide (NO) production of LPS-treated slices gradually increased from 5 to 24 h (24 h: 81+/-5 microM vs. 14+/-2 microM in control P < 0.05), paralleled by inducible nitric oxide synthase (iNOS) in the hepatocytes, iNOS mRNA was induced after 3 h. NO production but not iNOS induction was significantly inhibited by NOS inhibitors S-methylisothiourea and N(G)-nitro-L-arginine methylester. Both pentoxifylline and dexamethasone inhibited TNFalpha and IL-1beta production, albeit to a different extent, iNOS induction and, as a result thereof, NO production. CONCLUSIONS: These results imply that non-parenchymal cells in liver slices are viable and can be activated by LPS. In addition, it is concluded that the upregulation of iNOS in hepatocytes by LPS is caused by cytokines produced by Kupffer cells because inhibition of TNFalpha and IL-1beta production attenuated iNOS induction.

Alanine Transaminase↗
PubMed2001

Superior diagnostic strength of combined contrast enhanced MR-angiography and MR-imaging compared to intra-arterial DSA in liver transplantation candidates.

To evaluate the diagnostic value of combined contrast enhanced MRA (ce-MRA) and MRI compared to that of intra-arterial DSA (i.a.DSA) in liver transplantation, transjugular porto-systemic (TIPSS) and spleno-renal shunt candidates. 50 patients in the workup for liver transplantation underwent ce-MRA/MRI and i.a.DSA within a three days interval. Both examinations were assessed with respect to vessel anatomy and patency of the arterial, portal venous, porto-systemic collateral and systemic venous system. The results were compared with the intra-operative findings when available. Malignancy detection in ce-MRA/MRI and i.a.DSA were compared. There are no significant differences for the arterial part of the vascular supply to the liver that is important for transplantation. Although the differences for the portal system are not significant, the difference between the two techniques is of clinical importance because i.a.DSA failed to detect portal vein occlusion in 4 patients. Ce-MRA is significantly better for the detection of collaterals (p < 0.001) and the assessment of the inferior vena cava, the hepatic and the renal veins (p < 0.001). Although the detection of liver malignancy is poor in both techniques, ce-MRA/MRI is superior to i.a.DSA. This study shows that a one step diagnostic approach with a combination of ce-MRA and MRI is a valuable radiological tool with a superior diagnostic strength compared to i.a.DSA in the liver transplantation and shunt candidate. Therefore, ce-MRA/MRI should replace i.a.DSA in these patients groups.

Adolescent↗
PubMed2001

Expression of anti-OV6 antibody and anti-N-CAM antibody along the biliary line of normal and diseased human livers.

Following hepatic injury, proliferation of anastomosing ductules can be observed. The origin of this ductular reaction is not completely clear, although there is considerable evidence for proliferation of a putative hepatic progenitor cell, reported to be located in the canals of Hering (CoH) and showing morphologic similarities with rat oval cells. In this study, we analyzed the immunophenotype of solitary oval cell-like cells (SOC), intralobular groups of cuboidal cells that might represent lining cells of CoH, bile ductular cells (BDC), bile duct epithelial cells (BEC), and hepatocytes. We used the antibodies OV6, CK19, and CD56 (NCAM) in a double-staining method in a series of 111 liver specimens. The series consisted of a variety of liver diseases, primary liver tumors, and normal livers. In normal livers, SOC, CoH, BDC, and BEC were uniformly and predominantly CK19+, OV6+, and CD56-. In diseased livers SOC and BDC were CK19+, OV6+, and also CD56+. Occasionally, BEC was CD56+ in damaged bile ducts in diseased liver, e.g., PSC. CoH lining cells were not present in cirrhotic nodules and were indistinguishable from BDC in the fibrous septa. The consistent and uniform staining patterns of SOC, CoH, and BDC support the concept that these cells share the same biliary lineage and might represent one biliary structure. The expression of CD56 on these cells in diseased livers indicates that CD56 is a useful marker for a reparative or regenerative state of the biliary liver-cell constituents but not to discriminate a putative hepatic stem cell.

Antibodies↗
PubMed2001

Comparison of outcome after pediatric liver transplantation for metabolic diseases and biliary atresia.

UNLABELLED: Metabolic diseases (MD) are the second largest indication group for orthotopic liver transplantation (OLTx) in children after biliary atresia (BA). A better outcome after transplantation can be expected because of a better pretransplant condition and the absence of previous abdominal surgery. To prove this statement, patient survival, graft survival, and morbidity were compared between a group of 24 for MD and 52 for BA consecutively transplanted children. The actuarial one- and five-year patient survival rates for MD were 96% and 84%, and for BA 84% and 70%, respectively (p logrank test = 0.17). Three MD children (13%) and 15 BA children (29%) died. The actuarial one- and five-year graft survival rates for MD were 75% and 58%, and for BA 75% and 64%, respectively (p logrank test = 0.76). Seven MD children (29%) and 11 BA children (21%) were retransplanted. Postoperative bleeding and gastrointestinal complications occurred less frequent (4% vs. 18% and 4% vs. 14%, respectively), whereas biliary complications, viral infections, and acute rejection occurred more frequently (38% vs. 21%, 29% vs. 15%, and 50% vs. 37%, respectively) in MD children. The difference in the incidence of the various postoperative complications between both groups was not statistically significant. The mean ICU and ventilator stay was 7.5 and four days, respectively, in MD children and 16 and 10 days, respectively, in BA children (p = ns). The mean infection, complication, intervention, and retransplantation rate was equal in both groups. CONCLUSION: Mortality and morbidity after pediatric liver transplantation for MD and BA are not different despite the better starting point for children with MD.

Biliary Atresia↗
PubMed2001

Recombinant human interleukin-6 induces hepatocyte growth factor production in cancer patients.

BACKGROUND: Experiments in animals demonstrate an important role for interleukin-6 (IL-6) in liver regeneration. It is suggested that IL-6 initiates hepatocyte growth factor (HGF) synthesis. METHODS: The aim of the study was to examine the effect of exogenously administered recombinant human IL-6 (rhIL-6), in doses of 0.5, 1.0, 2.5, 5, 10 and 20 micrograms/kg/day, on HGF serum levels in humans. Serum HGF levels were measured on days 1, 2, 3, 8 and 15 and were correlated with serum amyloid A (SAA) and C-reactive protein (CRP). RESULTS: Median HGF levels increased to 124% at day 3 (P < 0.05) and 157% (P < 0.05) at day 8 as compared to 100% levels at day 1. An IL-6 dose-dependent increase in HGF was found at day 8 (R = 0.53, P < 0.02). The percentual change in serum HGF level at day 8 correlated with IL-6 serum levels at day 1 R = 0.59, P < 0.01). HGF levels did not correlate with CRP and SAA. CONCLUSION: In humans, rhIL-6 administration resulted in an increase in serum HGF levels.

Adult↗
PubMed2001

Pylorus-preserving pancreatoduodenectomy: influence of a Billroth I versus a Billroth II type of reconstruction on gastric emptying.

BACKGROUND/AIM: Delayed gastric emptying (DGE) is a frequent problem after pylorus-preserving pancreatoduodenectomy. Important risk factors are the presence of intra-abdominal complications. Searching for other causes, this study evaluates the influence of the type of reconstruction after a pancreatoduodenectomy (Billroth I vs. Billroth II; B I vs. B II on DGE. METHODS: A retrospective study was performed evaluating consecutive patients from two surgical institutes. 174 patients were included (B II type of reconstruction n = 123, period 1992-1996; B I type of reconstruction n = 51, period 1988-1998). DGE was defined by gastric stasis requiring nasogastric intubation for 10 days or more or the inability to tolerate a regular diet on or before the 14th postoperative day. RESULTS: After a B I type of reconstruction, there was significantly longer nasogastric intubation period as compared with a B II type of reconstruction (B I median 13 days, range 4-47, B II median 6 days, range 1-40; p < 0.05). There was no difference in postoperative commencement of a normal diet. Also significantly more patients had DGE after a B I (76%) as compared with a B II type of reconstruction (32%; p < 0.05). CONCLUSIONS: The results of this study indicate a significantly higher incidence of DGE after a B I type of reconstruction as compared with a B II type reconstruction. The etiology remains speculative.

Adult↗
PubMed2001

Cost effectiveness of selective decontamination of the digestive tract in liver transplant patients.

OBJECTIVE: To assess the cost effectiveness of selective decontamination of the digestive tract (SDD) in liver transplant patients. DESIGN: Randomised, placebo-controlled, double-blind trial with an integrated economic evaluation. SETTING: Two university hospitals in The Netherlands. Cost effectiveness was assessed from a societal perspective. PATIENTS AND PARTICIPANTS: 58 patients who underwent liver transplantation and received SDD (n = 29) or placebo (n = 29) pre- and postoperatively. INTERVENTIONS: SDD medication and placebo. MAIN OUTCOME MEASURES: Infection episodes, days of infection, costs of SDD and routine cultures, mean other direct medical costs per patient and additional costs of severe infection. RESULTS: Costs of SDD medicine and routine cultures were on average 3,100 US dollars ($US; 1997 values) per patient who underwent SDD. Both preoperatively and postoperatively, costs other than SDD and cultures did not significantly differ between the SDD and the placebo groups (preoperative, $US2,370 vs $US2,590; postoperative, $US25,455 vs $US24,915). Additional postoperative costs of severe infections were $US250 per day per patient. There were no significant differences in the mean number of infection episodes between groups. CONCLUSIONS: SDD leads to the additional costs of SDD medication and routine cultures, whereas no savings in other costs and no improvement in infection episodes are realised. Consequently, SDD may be considered as a nonefficient approach in patients undergoing liver transplantation. The additional costs of severe infection are considerable.

Adult↗
PubMed2001

Cellular distribution and handling of liver-targeting preparations in human livers studied by a liver lobe perfusion.

We developed and tested a novel method for perfusing parts of human liver to study uptake and handling of drug-targeting preparations. These preparations, designed for the treatment of liver fibrosis in man, have been extensively studied in animals, but little is known about the uptake and handling by human livers. Human liver tissue was obtained from livers procured from multiorgan donors and from cirrhotic livers of patients. To assess tissue viability, perfusate glutamate-oxalacetate-transaminase (GOT), glutamate-pyruvate-transaminase (GPT), and lactate dehydrogenase (LDH) levels were determined. To assess tissue functionality, the uptake of taurocholic acid and phase I and II metabolism of lidocaine and 7-hydroxycoumarin were determined. Uptake of a drug-targeting preparation was studied with Dexa10-HSA, which is designed for targeting of dexamethasone to nonparenchymal cells in the liver. During a 90-min perfusion period, no elevation of either GOT, GPT, or LDH was found. Both healthy control livers and cirrhotic livers showed phase I and II drug metabolism and functional taurocholic acid uptake. Studies with Dexa10-HSA revealed that 60 min after administration, 40% of the dose had been taken up by control livers and only 5% by cirrhotic livers. In control livers, Kupffer and endothelial cells had taken up Dexa10-HSA, whereas in cirrhotic livers only Kupffer cells were responsible for the uptake. Viability parameters and liver function tests clearly showed the applicability of this method. In the perfusion set-up, we showed uptake of the drug-targeting preparation Dexa10-HSA by healthy and cirrhotic human liver tissue, although the distribution patterns differed. This demonstrates the need to study new concepts in (diseased) human tissue.

Anesthetics, Local↗
PubMed2001

Cellular distribution and handling of liver-targeting preparations in human livers studied by a liver lobe perfusion.

We developed and tested a novel method for perfusing parts of human liver to study uptake and handling of drug-targeting preparations. These preparations, designed for the treatment of liver fibrosis in man, have been extensively studied in animals, but little is known about the uptake and handling by human livers. Human liver tissue was obtained from livers procured from multiorgan donors and from cirrhotic livers of patients. To assess tissue viability, perfusate glutamate-oxalacetate-transaminase (GOT), glutamate-pyruvate-transaminase (GPT), and lactate dehydrogenase (LDH) levels were determined. To assess tissue functionality, the uptake of taurocholic acid and phase I and II metabolism of lidocaine and 7-hydroxycoumarin were determined. Uptake of a drug-targeting preparation was studied with Dexa(10)-HSA, which is designed for targeting of dexamethasone to nonparenchymal cells in the liver. During a 90-min perfusion period, no elevation of either GOT, GPT, or LDH was found. Both healthy control livers and cirrhotic livers showed phase I and II drug metabolism and functional taurocholic acid uptake. Studies with Dexa(10)-HSA revealed that 60 min after administration, 40% of the dose had been taken up by control livers and only 5% by cirrhotic livers. In control livers, Kupffer and endothelial cells had taken up Dexa(10)-HSA, whereas in cirrhotic livers only Kupffer cells were responsible for the uptake. Viability parameters and liver function tests clearly showed the applicability of this method. In the perfusion set-up, we showed uptake of the drug-targeting preparation Dexa(10)-HSA by healthy and cirrhotic human liver tissue, although the distribution patterns differed. This demonstrates the need to study new concepts in (diseased) human tissue.

Anesthetics, Local↗