136 results on '"Slooff, MJH"'
Search Results
2. Surgical treatment of giant haemangioma of the liver
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Brouwers, M.A.M., Peeters, PMJG, de Jong, KP, Haagsma, EB, Klompmaker, IJ, Bijleveld, CMA, Zwaveling, JH, Slooff, MJH, Groningen Institute for Organ Transplantation (GIOT), and Guided Treatment in Optimal Selected Cancer Patients (GUTS)
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body regions ,TRANSPLANTATION ,HEPATIC HEMANGIOMAS ,MANAGEMENT ,ENUCLEATION ,Surgery ,EMBOLIZATION ,THERAPY ,CAVERNOUS HEMANGIOMA - Abstract
Background The treatment of giant symptomatic haemangioma of the liver is still controversial. This retrospective study reviewed the results of surgical treatment. Methods Twenty-eight patients with symptomatic giant haemangioma of the liver were treated by liver resection (n = 24) or liver transplantation (n = 4). The median diameter of the haemangiomas was 11 (range 5-20) cm. Results Complications occurred in five of the 24 patients treated by partial liver resection, although all survived and remain alive and well more than 2 years after surgery. In six patients there was residual haemangioma in the liver remnant which did not enlarge during the 2-year follow-up. In four patients the haemangioma was considered irresectable and liver transplantation was performed. One died after a 'two-stage' liver transplantation; the remaining three patients are alive and well, 1, 4 and 9 years after transplantation. Conclusion Liver resection is the treatment of choice for giant haemangioma of the liver where possible. In selected cases liver transplantation is indicated.
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- 1997
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3. Evaluation of experimental internal rectus sheath vascular autograft in dogs
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Nemeth, T, Kobori, L, Dallos, G, Nemes, B, Jaray, J, Perner, F, Manczur, F, Hetyei, C, Slooff, MJH, de Jong, KP, Groningen Institute for Organ Transplantation, and Guided Treatment in Optimal Selected Cancer Patients
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MODEL ,ARTERIAL AUTOGRAFT ,SURGERY ,AUTOLOGOUS PERITONEUM ,GRAFT ,RECONSTRUCTION ,SUBSTITUTE ,DEFECTS ,LIVER-TRANSPLANTATION ,EFFICACY - Abstract
Examinations were done on 16 experimental dogs. Autologous vascular grafting developed from internal rectus sheath was performed on both sided external iliac arteries (32 anastomoses). Dogs in group I.1. were heparinised, the individuals in II.1. were treated with Cyclosporine. Acetyl-salicylate anticoagulation therapy was administered in group I.2., which was also combined with Cyclosporine in group II.2. There was no technical difficulty neither during the development nor during the implantation of the grafts. Perioperative complication was not experienced either. In the postoperative period the physical and the Doppler ultrasonographic examination revealed well correlated results. In group I.1., I.2. and II.1. 2 of each suffered from either obturation by thrombotisation (I.1.) or stenosis at proximal anastomosis (I.2., II.1.). Grafts remained patent at 370 cm/sec flow rate detected and measured by Doppler. All grafts of group II.2. remained patent with an average of 383 cm/sec arterial flow rate. Macroscopic and histopathological evaluation of graft quality 3 months after implantation revealed that patent conduits pulsated normally showing an average of 1,5 mm widening of the lumen during reoperation. Mesothelial layer originated from the rectus sheath was detected just in spots by histopathology. Certain transformation process was dominant characterised by development of proendothelial monolayer from the site of anastomoses covering mostly the entire inner surface of the graft. Elastic fibers as well as smooth muscle structures were found within the wall of the grafts in histology proving angiogenetic processes. Fibrin and small vessels were also detected with fibrin-collagen staining. The positive result of the von Willebrandt staining proved the appearance of proendothelial monolayer in immunohistochemistry. The electromicroscopic examination confirmed the presence of intact fibrin and elastic fibers as well as actin and well structured mitochondria as evidence of proper tissue oxygenisation. Cyclosporine was not proved to have degenerative effect on the rectus sheath graft.
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- 2005
4. Inflammatory bowel disease after liver transplantation: the effect of different immunosuppressive regimens
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Haagsma, EB, Van den Berg, AP, Kleibeuker, JH, Slooff, MJH, Dijkstra, G, Faculteit Medische Wetenschappen/UMCG, Guided Treatment in Optimal Selected Cancer Patients (GUTS), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Groningen Institute for Organ Transplantation (GIOT), and Translational Immunology Groningen (TRIGR)
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RECIPIENTS ,MICE ,surgical procedures, operative ,ULCERATIVE-COLITIS ,FEATURES ,AUTOIMMUNITY ,TACROLIMUS ,PRIMARY SCLEROSING CHOLANGITIS - Abstract
Background: Seemingly conflicting results have been reported on the prevalence and severity of inflammatory bowel disease after liver transplantation. Regimens with different combinations of drugs can be used for immunosuppression after transplantation. Aim: To study retrospectively the prevalence of inflammatory bowel disease after liver transplantation, and the possible relationship with maintenance immunosuppressive regimens. Methods: All 78 patients with end-stage primary sclerosing cholangitis (48 patients) or autoimmune cirrhosis (30 patients), transplanted between 1979 and July 2001, and with a follow-up of at least 1 year, were eligible for this study. In addition to patient and transplant characteristics, data on inflammatory bowel disease and immunosuppression before and after transplantation were collected. The Kaplan-Meier method was used for survival analysis. Possible risk factors for inflammatory bowel disease after transplantation were analysed by Cox univariate and multivariate regression. Results: The median follow-up after transplantation was 7.2 years (range, 1.1-22.3 years). Nine of 25 patients with pre-transplant inflammatory bowel disease experienced flare-ups after transplantation. Six of 53 patients without pre-transplant inflammatory bowel disease developed de novo inflammatory bowel disease after transplantation. The cumulative risks (standard errors in parentheses) for inflammatory bowel disease were 6% (3%), 12% (4%) and 20% (5%) at 1, 3 and 5 years after transplantation, respectively. The inflammatory bowel disease-free survival was significantly higher in patients not receiving tacrolimus vs. those receiving tacrolimus, in patients receiving azathioprine vs. those not receiving azathioprine and in patients taking the regimen prednisolone-azathioprine-ciclosporin A vs. those taking tacrolimus-prednisolone. Pre-transplant inflammatory bowel disease and the use of tacrolimus were found to be independent predictors for inflammatory bowel disease after transplantation. Conclusions: The prevalence of inflammatory bowel disease after liver transplantation is affected by the immunosuppression used. Azathioprine seems to have a protective effect and tacrolimus a promoting effect.
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- 2003
5. Recombinant factor Vlla in orthotopic liver transplantation: influence on parameters of coagulation and fibrinolysis
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Meijer, K, Hendriks, HGD, de Wolf, JTM, Klompmaker, IJ, Lisman, T, Hagenaars, AAM, Slooff, MJH, Porte, RJ, van der Meer, J, Faculteit Medische Wetenschappen/UMCG, Groningen Institute for Organ Transplantation (GIOT), and Vascular Ageing Programme (VAP)
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ACTIVATION ,TRANSFUSION REQUIREMENTS ,TISSUE FACTOR ,BLOOD-LOSS ,orthotopic liver transplantation ,thrombin generation ,fibrinolysis ,coagulation ,FACTOR-VIIA ,recombinant factor Vlla ,RFVIIA - Abstract
The effect of recombinant factor Vila (rFVIIa) on blood loss was evaluated in cirrhotic patients undergoing orthotopic liver transplantation. In the present study, we explored the effect of rFVIIa on coagulation and fibrinolysis during orthotopic liver transplantation. Coagulation factors, parameters of thrombin generation and parameters of fibrinolysis were measured in six patients who had received a single dose of 80 mug/kg rFVIIa and in ten controls, during and after orthotopic liver transplantation. Baseline concentrations and course of coagulation factors were similar in patients and controls. Thrombin generation did not rise after the administration of rFVIIa, but showed a sharp increase after reperfusion in patients, as compared with controls. No difference in fibrinolysis was apparent between patients and controls. No evidence of diffuse intravascular coagulation was seen. We conclude that the use of rFVIIa in orthotopic liver transplantation seems to enhance thrombin generation in a localized and time-limited matter, without causing systemic coagulation. (C) 2003 Lippincott Williams Wilkins.
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- 2003
6. The cost effectiveness of lung transplantation compared with that of heart and liver transplantation in the Netherlands
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Ouwens, JP, van Enckevort, PJ, TenVergert, EM, Bonsel, GJ, van der Bij, W, Haagsma, EB, Rutten, FFH, Slooff, MJH, Koeter, GH, Other departments, Faculteit Medische Wetenschappen/UMCG, and Groningen Institute for Organ Transplantation (GIOT)
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LIFE ,Transplantation ,surgical procedures, operative ,liver transplantation ,cost-benefit analysis ,lung transplantation ,PROGRAM ,heart transplantation - Abstract
This study was performed to assess the main reasons for the unfavorable cost effectiveness of lung transplantation compared with that of heart and liver transplantation. Costs, effects, and cost-effectiveness ratios of Dutch lung, heart, and liver transplantation programs were compared. The data are based on three Dutch technology assessments of transplantation, with minor adjustments for time and methods. In result, mainly follow-up costs of lung transplantation are higher than costs of heart and liver transplantation - US $150,300, US $121,500, and US $95,300, respectively - in the first 3 years after transplantation. The survival gain realized by lung transplantation is small (4.4 years) compared with heart (8.8 years) and liver (14.7years) transplantation. Costs per life-year gained were US $77,000, US $38,000, and US $26,000 for lung, heart, and liver transplantation, respectively. The unfavorable cost effectiveness of lung transplantation is largely related to a relatively small survival gain and high follow-up costs.
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- 2003
7. Hyperkalaemia after radiofrequency ablation of hepatocellular carcinoma
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Verhoevena, BH, Haagsma, EB, Appeltans, BMG, Slooff, MJH, de Jong, KP, Groningen Institute for Organ Transplantation (GIOT), and Guided Treatment in Optimal Selected Cancer Patients (GUTS)
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RFA ,side effects ,hyperkalaemia ,TUMOR LYSIS SYNDROME ,CRYOABLATION ,potassium ,arrhythmia ,HEPATIC MALIGNANCIES - Abstract
Radiofrequency ablation of liver tumours is a useful therapy for otherwise unresectable tumours. The complication rate is said to be low. In this case report we describe hyperkalaemia after radiofrequency ablation of a hepatocellular carcinoma in a patient with end-stage renal insufficiency. (C) 2002 Lippincott Williams Wilkins.
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- 2002
8. Selective bowel decontamination in elective liver transplantation: no improvement in endotoxaemia, initial graft function and post-operative morbidity
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Maring, JK, Zwaveling, JH, Klompmaker, IJ, Slooff, MJH, and Faculteit Medische Wetenschappen/UMCG
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musculoskeletal diseases ,endotoxin ,RECIPIENTS ,liver transplantation ,selective decontamination ,POSTREPERFUSION SYNDROME ,CIRCULATING ENDOTOXINS ,translocation ,initial poor function ,DONOR ,TNF-ALPHA ,DYSFUNCTION - Abstract
Peri-operative endotoxaemia during liver transplantation has been linked to compromised graft function and infection. Selective decontamination of the digestive tract (SDD) could prevent endotoxaemia by eradicating Gram-negative bacteria from the intestine. In a randomized placebo controlled study we investigated the effects of endotoxaemia and the efficacy of SDD to prevent its occurrence. Thirty-one patients undergoing elective orthotopic liver transplantation received either SDD (n = 15) or placebo (n = 16), which was started at least 7 days before transplantation. Endotoxin levels were measured in blood peroperatively. Patients were scored daily for signs of liver dysfunction and infection. Endotoxaemia was neither associated with initial poor function nor any routine liver function test. Infections were more prominent in patients without endotoxaemia. SDD did not prevent endotoxaemia. Endotoxaemia does not affect post-operative graft function or the incidence of post-operative infections. SDD cannot prevent peri-operative endotoxaemia. Translocation of endotoxin may not be relevant in liver transplantation.
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- 2002
9. Effects of recombinant activated factor VII on coagulation measured by thromboelastography in liver transplantation
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Hendriks, HGD, Meijer, K, de Wolf, JTM, Porte, RJ, Klompmaker, IJ, Lip, H, Slooff, MJH, van der Meer, J, Faculteit Medische Wetenschappen/UMCG, Groningen Institute for Organ Transplantation (GIOT), and Vascular Ageing Programme (VAP)
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FACTOR-X ,liver transplantation ,TISSUE FACTOR ,hemostasis ,thromboelastography ,fibrinolysis ,recombinant activated factor VII ,coagulation ,PROTHROMBIN TIME ,circulatory and respiratory physiology - Abstract
Besides the conventional laboratory tests, thromboelastography (TEG) is used to monitor hemostasis during liver transplantation. A previous pilot study suggested a beneficial effect of recombinant activated factor VII (rFVIIa) on transfusion requirements in liver transplantation. In the present study, we assess the effects of rFVIIa on coagulation variables and TEG. In six study patients, the prothrombin time (PT), the activated partial thromboplastin time (aPTT) and TEG variables [reaction time (r), kinetic time (k), or clot formation time, a angle (a), and maximal amplitude (MA)] were recorded before and after the administration of a bolus of 80,mug/kg rFVIIa. These patients were compared with six controls who did not receive rFVIIa. In contrast with the control group, a significant shortening of PT (P = 0.028) and aPTT (P = 0.028), r (P = 0.046) and k (P = 0.043) values, and a significant incline of the a angle (P = 0.028) were noticed after injection of rFVIIa, whereas MA increased not significantly (P = 0.075). rFVIIa rapidly improved coagulation variables in liver transplant patients including PT and aPTT. Of the TEG variables, r, k and a angle significantly improved, and MA showed a trend to increase. These data suggest that rFVIIa not only influences the speed of clot formation, but also the physical properties of the clot, which cannot be detected by routine coagulation tests.
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- 2002
10. Selective decontamination of the digestive tract to prevent postoperative infection: A randomized placebo-controlled trial in liver transplant patients
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Zwaveling, JH, Maring, JK, Klompmaker, IJ, Haagsma, EB, Bottema, JT, Winter, Heinrich L.J., van Enckevort, PJ, TenVergert, EM, Metselaar, HJ, Bruining, HA, Slooff, MJH, Faculteit Medische Wetenschappen/UMCG, and Groningen Research Institute of Pharmacy
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BACTERIAL ,liver transplantation ,cost effectiveness ,Gram-positive bacterial infection ,fungal infection ,MORTALITY ,costs ,BOWEL DECONTAMINATION ,colonization ,infection ,INTENSIVE-CARE UNIT ,selective decontamination ,postoperative complications ,FAILURE ,Gram-negative bacterial infection ,sepsls - Abstract
Objective., To determine the efficacy of selective decontamination of the digestive tract (SDD) in patients undergoing elective transplantation of the liver. Design: Randomized, double-blind, placebo-controlled study. Setting. Two academic teaching hospitals. Patients. Adult patients undergoing elective liver transplantation: 26 patients receiving SDD and 29 patients receiving a placebo. Interventions: Patients undergoing SDD were administered 400 mg of norfloxacin once daily as soon as they were accepted for transplantation, Postoperative treatment for this group consisted of 2 mg of colistin, 1.8 mg of tobramycin, and 10 mg of amphotericin B, four times daily, combined with an oral paste containing a 2% solution of the same drugs until postoperative day 30. Prophylactic Intravenous administration of antibiotics was not part of the SDD regimen in this study. Control patients were given a similar regimen with placebo drugs. Measurements: The mean number of postoperative bacterial and fungal infections in the first 30 days after transplantation was the primary efficacy end point. Days on a ventilator, days spent in the intensive care unit, and medical costs were registered as secondary outcome variables. Main Results. Of the 26 patients undergoing SOD, 22 (84.5%) developed an infection in the postoperative study period; In the placebo group (n = 29), these numbers were not significantly different (25 patients, 86%). The mean number of postoperative infectious episodes per patient was also not significantly different: 1.77 (SDD) vs. 1.93 (placebo), Infections Involving Gram-negative aerobic bacteria and Candida species were significantly less frequent in patients receiving SOD (p Conclusions. Selective decontamination of the digestive tract does not prevent Infection in patients undergoing elective liver transplantation and increases the cost of their care. It does, however, affect the type of infection. Infections with Gram-negative bacilli and with Candida species are replaced by infections with Gram-positive cocci.
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- 2002
11. Genogrouping and incidence of virulence factors of Enterococcus faecalis in liver transplant patients differ from blood culture and fecal isolates
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Waar, K, Muscholl-Silberhorn, AB, Slooff, MJH, Harmsen, HJM, Degener, JE, Willems, Rob J. L., Man, Biomaterials and Microbes (MBM), and Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI)
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SURFACE PROTEIN ,INFECTIONS ,AGGREGATION SUBSTANCE ,HEMOLYSIN ,ANTIBIOTIC-RESISTANCE ,DNA ,BACTERIAL SEX-PHEROMONE ,STREPTOCOCCUS-FAECALIS ,CONJUGAL TRANSFER ,PLASMID - Abstract
Enterococcus faecalis is a leading cause of infections in liver transplant patients. This study reviewed the incidence of virulence factors such as hemolysin, gelatinase, aggregation substances (asa1 and asa373), or the enterococcal surface protein (Esp) in isolates from liver transplant patients. In total, 133 isolates from liver transplant patients were compared with 47 isolates from feces of healthy volunteers and 66 isolates from blood cultures. Amplified fragment length polymorphism (AFLP) analysis indicates that the isolates from different clinical subgroups can be divided into genogroups with an AFLP similarity of. > 80% and different virulence factors. Hemolysin and asa1 might be associated with infection, as they are more frequent in isolates from blood cultures and transplant patients. Esp might be associated with colonization and spread, because it is more frequent in isolates from feces of healthy volunteers and transplant patients. An epidemic esp gene-positive strain among liver transplant patients supports this hypothesis.
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- 2002
12. Graft loss after pediatric liver transplantation
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Sieders, E, Peeters, PMJG, TenVergert, EM, de Jong, KP, Porte, RJ, Zwaveling, JH, Bijleveld, CMA, Gouw, ASH, Slooff, MJH, Groningen Institute for Organ Transplantation (GIOT), and Guided Treatment in Optimal Selected Cancer Patients (GUTS)
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RECIPIENTS ,MORBIDITY ,surgical procedures, operative ,DONOR LIVER ,SIZE ,FULMINANT HEPATIC-FAILURE ,TACROLIMUS FK506 ,INFECTION ,RISK-FACTORS ,SURVIVAL ,CHILDREN - Abstract
Objective To describe the epidemiology and causes of graft loss after pediatric liver transplantation and to identify risk factors. Summary Background Data Graft failure after transplantation remains an important problem. It results in patient death or retransplantation, resulting in lower survival rates. Methods A series of 157 transplantations in 120 children was analyzed. Graft loss was categorized as early (within 1 month) and late (after 1 month). Risk factors were identified by analyzing recipient, donor, and transplantation variables. Results Kaplan-Meier 1-month and 1 -, 3-, and 5-year patient survival rates were 85%, 82%, 77%, and 71%, respectively, Graft survival rates were 71%, 64%, 59%, and 53%, respectively. Seventy-one of 157 grafts (45%) were lost 18 (25%) by death of patients with functioning grafts and 53 (75%) by graft-related complications. Forty-five grafts (63%) were lost early after transplantation. Main causes of early loss were vascular complications, primary nonfunction, and patient death. Main cause of late graft loss was fibrosis/cirrhosis, mainly as a result of biliary complications or unknown causes, Child-Pugh score, anhepatic phase, and urgent transplantation were risk factors for early loss, Donor age, clonor/recipient weight ratio, blood loss, and technical-variant liver grafts were risk factors for late loss, Conclusions To prevent graft loss after pediatric liver transplantation, potential recipients should be referred early so they can be transplanted in an earlier phase of their disease, Technical-variant liver grafts are risk factors for graft survival. The logistics of the operation need to be optimized to minimize the length of the anhepatic phase.
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- 2002
13. Aprotinin: Safe and effective in all patients undergoing orthotopic liver transplantation?
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Porte, RJ, Slooff, MJH, and Groningen Institute for Organ Transplantation (GIOT)
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PRIMARY BILIARY-CIRRHOSIS ,DOUBLE-BLIND ,REDUCTION ,TRANSFUSION REQUIREMENTS ,BLOOD-LOSS ,MULTICENTER ,FIBRINOLYSIS ,COAGULATION ,PRESERVATION ,PRODUCTS - Published
- 2001
14. Cellular distribution and handling of liver-targeting preparations in human livers studied by a liver lobe perfusion
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Melgert, BN, Olinga, P, Weert, B, Slooff, MJH, Meijer, DKF, Poelstra, K, Groothuis, GMM, Groningen University Institute for Drug Exploration (GUIDE), Nanomedicine & Drug Targeting, Nanotechnology and Biophysics in Medicine (NANOBIOMED), Biopharmaceuticals, Discovery, Design and Delivery (BDDD), Groningen Research Institute for Asthma and COPD (GRIAC), and Groningen Institute for Organ Transplantation (GIOT)
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SLICES ,HUMAN HEPATOCYTES ,TRANSPLANTATION ,ENDOCYTOSIS ,INVIVO ,RAT-LIVER ,DRUGS ,ALBUMIN ,ENDOTHELIAL-CELLS ,CIRRHOSIS - Abstract
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.
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- 2001
15. Rapid decreases in donor-specific cytotoxic T lymphocyte precursor frequencies and graft outcome after liver and lung transplantation
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de Haan, A, van den Berg, AP, van der Bij, W, Hepkema, BG, Bruin-van Dijk, E, van der Gun, [No Value], Lems, SPM, Slooff, MJH, Haagsma, EB, de Leij, LFMH, Prop, J, Faculteit Medische Wetenschappen/UMCG, University of Groningen, and Groningen Institute for Organ Transplantation (GIOT)
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KIDNEY ALLOGRAFT ,surgical procedures, operative ,LIMITING DILUTION ,FUNCTIONAL DELETION ,ANTIGEN-SPECIFIC HYPOREACTIVITY ,BRONCHIOLITIS OBLITERANS SYNDROME ,ALLOGRAFT RECIPIENTS ,CHRONIC REJECTION ,PERIPHERAL-BLOOD ,SUPPRESSOR CELLS ,TOLERANCE INDUCTION - Abstract
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 (Rnp) 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.
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- 2001
16. Reduced transfusion requirements by recombinant factor VIIa in orthotopic liver transplantation - A pilot study
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Hendriks, HGD, de Wolf, JTM, Klompmaker, IJ, Porte, RJ, de Kam, PJ, Hagenaars, AJM, Melsen, T, Slooff, MJH, van der Meer, J, Faculteit Medische Wetenschappen/UMCG, and Groningen Institute for Organ Transplantation (GIOT)
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VASCULAR COMPLICATIONS ,SELECTIVE USE ,BLOOD ,TISSUE FACTOR ,ACTIVATED FACTOR-VII ,VENOVENOUS BYPASS ,APROTININ ,HEMOSTASIS ,PROTHROMBIN - Abstract
Background. Large transfusion requirements, i.e., excessive blood loss, during orthotopic liver transplantation (OLT) are correlated with increased morbidity and mortality, Recombinant factor VIIa (rFVIIa) 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 mug/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). flood 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 mug/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.
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- 2001
17. The applicability of rat and human liver slices to the study of mechanisms of hepatic drug uptake
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Olinga, P, Hof, IH, Smit, M, de Jager, MH, Swart, PJ, Slooff, MJH, Meijer, DKF, Groothuis, GMM, Merema, M.T., Groningen University Institute for Drug Exploration (GUIDE), Nanomedicine & Drug Targeting, Biopharmaceuticals, Discovery, Design and Delivery (BDDD), and Groningen Institute for Organ Transplantation (GIOT)
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ALBUMINS ,lucigenin ,HUMAN HEPATOCYTES ,modified albumins ,digoxin ,VIABILITY ,TRANSPORT ,rhodamine B ,BILE-ACID ,SERUM - Abstract
In the present study we investigated the applicability of the liver slice model to study mechanisms of drug uptake. Four model compounds were investigated that enter hepatocytes via entirely different membrane transport mechanisms. Rhodamine B (RB), which enters hepatocytes by passive diffusion, was homogeneously distributed throughout the rat liver slice (250 mum thickness) within 5 min, indicating that the penetration rate into the slice and the diffusion rate into the cells are rapid. In contrast, lucigenin (LU), which is taken up by hepatocytes through adsorptive endocytosis, was detected in the inner cell layers after 15 min. Digoxin uptake into the slice showed a temperature-dependent component and was stereos electively inhibited by quinine, which is compatible with the involvement of a carrier-mediated uptake mechanism. The neo-glycoalbumin Lactose(27)-Human Serum Albumin (Lact(27)-HSA) and the negatively charged Succinylated-Human Serum Albumin (Suc-HSA) entered the slices and were taken up temperature-dependently into hepatocytes and endothelial cells, respectively. The liver slice preparation is a valuable tool to investigate the mechanisms of cellular uptake of drugs. Moreover, the precision-cut liver slices offer the unique possibility to study both hepatocyte and endothelial cell function in human and rat liver. (C) 2001 Elsevier Science Inc. All rights reserved.
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- 2001
18. Cost effectiveness of selective decontamination of the digestive tract in liver transplant patients
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van Enckevort, PJ, Zwaveling, JH, Bottema, JT, Maring, JK, Klompmaker, IJ, Slooff, MJH, TenVergert, EM, and Faculteit Medische Wetenschappen/UMCG
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musculoskeletal diseases ,CONTROLLED TRIAL ,DOUBLE-BLIND ,BACTERIAL ,INTENSIVE-CARE UNIT ,INFECTIONS ,MULTIPLE TRAUMA PATIENTS ,health care economics and organizations ,COLONIZATION - Abstract
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 3100 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, $US2370 vs $US2590; 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.
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- 2001
19. The capability of isolated hepatocytes and liver slices of donor livers to predict graft function after liver transplantation
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Olinga, P, Maring, JK, Hof, IH, Slooff, MJH, Meijer, DKF, Groothuis, GMM, Merema, M.T., Groningen University Institute for Drug Exploration (GUIDE), Nanomedicine & Drug Targeting, Biopharmaceuticals, Discovery, Design and Delivery (BDDD), and Groningen Institute for Organ Transplantation (GIOT)
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drug transport ,surgical procedures, operative ,viability ,ACID ,graft function ,human hepatocytes ,RISK-FACTORS ,SELECTION CRITERIA ,REPERFUSION ,PRESERVATION ,liver slices ,drug metabolism - Abstract
Aims/Background: In liver transplantation, adequate function tests for donor livers and transplanted livers are of utmost importance to provide an objective basis for decision-making. Isolated hepatocyte and/or slice preparations from human donor liver tissue may be suitable to test the quality of the organ to be transplanted. Methods: Surgical waste material remaining after reduced size or split liver transplantation in children was used to prepare slices and isolated hepatocytes. The viability of these preparations as well as drug transport and metabolism functions were determined and related to graft function in 32 liver recipients. Results: The in vitro tests used in the present study apparently did not select non-viable livers. In vitro preparations of the primary non-function grafts which occurred in the investigated group showed normal viability, metabolic and uptake function. Conclusion: These results indicate that either the presently used viability tests are not sensitive enough to detect potential organ failure or that other factors besides the hepatocyte viability at the time of transplantation are of paramount importance to the graft function of the recipient, such as complications during and after transplantation or the viability of the non-parenchymal cells.
- Published
- 2000
20. End-stage liver disease as the only consequence of a mitochondrial respiratory chain deficiency: no contra-indication for liver transplantation
- Author
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Rake, JP, van Spronsen, FJ, Visser, G, Ruitenbeek, W, Schweizer, JJ, Bijleveld, CMA, Peeters, PMJG, de Jong, KP, Slooff, MJH, Reijngoud, DJ, Niezen-Koning, KE, Smit, GPA, Faculteit Medische Wetenschappen/UMCG, Groningen Institute for Organ Transplantation (GIOT), Guided Treatment in Optimal Selected Cancer Patients (GUTS), and Center for Liver, Digestive and Metabolic Diseases (CLDM)
- Subjects
LACTIC ACIDEMIA ,liver transplantation ,end-stage liver disease ,DISORDERS ,CHILDHOOD ,HEPATIC-FAILURE ,CHOLESTASIS ,inborn errors of metabolism ,DNA ,NEONATAL-ONSET ,mitochondrial respiratory chain deficiency ,OXIDATIVE-PHOSPHORYLATION ,DEPLETION ,CYTOPATHY - Abstract
The prerequisite for liver transplantation as a therapeutic option for inherited metabolic diseases should be that the enzyme defect, being responsible for the major clinical (hepatic and/or extra-hepatic) abnormalities, is localised in the liver. Furthermore? no adequate dietary or pharmacological treatment should be available or such treatment should have an unacceptable influence on the quality of life. We report an infant, who developed end-stage liver disease with persistent lactic acidaemia in his first months of life. Analysis of the mitochondrial respiratory chain in liver tissue revealed a combined partial complex I and IV deficiency. No extra-hepatic involvement could be demonstrated by careful screening for multiple organ involvement, including analysis of the mitochondrial respiratory chain in muscle tissue and cultured skin fibroblasts. The boy received a reduced size liver graft at the age of 8 months. He recovered successfully. almost 5 years after transplantation he is in good clinical condition. No clinical or biochemical signs of any organ dysfunction have been demonstrated. The considerations on which basis it was decided that there was no contra-indication to perform liver transplantation in this patient are discussed. Conclusion The possibility of a mitochondrial respiratory chain deficiency should be considered in liver disease of unknown origin prior to liver transplantation. Liver transplantation is a therapeutic option in mitochondrial respiratory chain deficiency-based end-stage liver disease provided that extra-hepatic involvement is carefully excluded.
- Published
- 2000
21. Endotoxins and cytokines during liver transplantation: Changes in plasma levels and effects on clinical outcome
- Author
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Maring, JK, Klompmaker, IJ, Zwaveling, JH, van der Meer, J, Limburg, PC, and Slooff, MJH
- Subjects
IL-6 ,INTERLEUKIN-6 ,SERUM LEVELS ,SPLANCHNIC ENDOTOXIN ,INJURY ,FACTOR-ALPHA ,RAT ,HEPATIC ISCHEMIA-REPERFUSION ,TNF-ALPHA ,TUMOR-NECROSIS-FACTOR - Abstract
Endotoxins, tumor necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1), and IL-6 are believed to have a key role in liver transplantation, The origin and course of these factors is not completely known. In this prospective study of 40 patients, we sought more understanding of the relations between these factors and their effects on clinical outcome by sampling at different sites. Endotoxemia was only present in 20% of the patients, In 75% of these patients, it was present during the anhepatic phase and quickly resolved after reperfusion, Endotoxemia was not related to a clinical adverse event, TNF-alpha was released from the graft after reperfusion, and initial levels after reperfusion were related to predonation levels in the donor. Only levels of TNF-alpha in the recipient before transplantation were found to be predictive of postoperative complications, We conclude that monitoring endotoxins and these cytokines is of very limited value in predicting outcome.
- Published
- 2000
22. Scanning electron microscopic analysis of endothelial cell coverage and quality in large vessels from multi-organ donors: effects of preservation on endothelial cell integrity
- Author
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van Leeuwen, EBM, Molema, G, van Luyn, MJA, de Jong, KP, Dijk, F, Slooff, MJH, Ruiters, MHJ, van der Meer, J, Groningen University Institute for Drug Exploration (GUIDE), Nanotechnology and Biophysics in Medicine (NANOBIOMED), Restoring Organ Function by Means of Regenerative Medicine (REGENERATE), Vascular Ageing Programme (VAP), Groningen Institute for Organ Transplantation (GIOT), Guided Treatment in Optimal Selected Cancer Patients (GUTS), Groningen Kidney Center (GKC), and Critical care, Anesthesiology, Peri-operative and Emergency medicine (CAPE)
- Subjects
preservation ,donor vessels ,LIVER-TRANSPLANTATION ,endothelial cells ,DYSFUNCTION ,iliac vessels ,AGE ,INJURY ,GRAFTS ,human ,scanning electron microscopy ,thrombosis ,transplantation ,ARTERY - Abstract
Endothelial cell integrity (coverage and quality) of large donor vessels is important because these vessels are used for vascular reconstructions in solid-organ transplantation. Disruption of the endothelial cell monolayer will initiate blood coagulation and may lead to thrombosis of large vessels, often resulting in the loss of the transplanted organ. Iliac arteries and veins, removed from 10 heart-beating multi-organ donors at the end of the donor procedure. were analyzed using scanning electron microscopy at three different rime points of preservation. Endothelial cell coverage and quality were determined immediately after removal from the donor, after 10 h (time of transplantation) and 7 d storage in 'University of Wisconsin' cold preservation solution (UW). Endothelial cell coverage decreased during the preservation of arteries, but was maintained in veins. Storage of the veins for 7 d in plastic bags showed a decreased endothelial cell coverage compared to storage in glass vials. Early removal of the blood vessels and proper storage, free floating and in clean UW, may improve maintenance of the endothelial cell integrity. These findings may be important in order to reduce the risk of thrombosis and, consequently, organ failure after transplantation. Furthermore, vessels with maintained endothelial cell integrity after 7 d may be used for in vitro research.
- Published
- 2000
23. Early vascular complications after pediatric liver transplantation
- Author
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Sieders, E, Peeters, PMJG, Ten Vergert, EM, de Jong, KP, Porte, RJ, Zwaveling, JH, Bijleveld, CMA, Slooff, MJH, Faculteit Medische Wetenschappen/UMCG, Groningen Institute for Organ Transplantation (GIOT), and Guided Treatment in Optimal Selected Cancer Patients (GUTS)
- Subjects
SURVIVAL ,GRAFT ,VEIN ,HEPATIC-ARTERY THROMBOSIS ,INFANTS ,DONORS ,RECONSTRUCTION ,CHILDREN - Abstract
Vascular complications have a detrimental effect on the outcome after liver transplantation. Most studies focus exclusively on hepatic artery thrombosis (HAT), The current study analyzed the incidence, consequences, and risk factors for HAT, portal vein thrombosis (PVT), and venous outflow tract obstruction (VOTO) in a consecutive series of 157 pediatric liver transplantations. The overall incidence of vascular complications was 21%. The incidences of HAT, PVT, and VOTO were 10%, 4%, and 6%, respectively. Patient survival after PVT and VOTO and graft survival after HAT and PVT were less compared with survival of grafts without vascular complications. To identify risk factors for vascular complications, factors related to recipient, donor, and surgical techniques were analyzed. A low donor-recipient (D/R) age ratio, long surgical time, and use of the proper hepatic artery of the recipient for arterial reconstruction were risk factors for HAT. Young age, low weight, segmental grafts, and piggyback technique were risk factors for PVT Fulminant hepatic failure, high D/R age and weight ratios, and use of segmental grafts were related to VOTO. Vascular complications, which occurred in 21% of the pediatric liver transplantations, had a significant impact on patient and graft survival. Size disparity between donor and recipient was an important risk factor for vascular complications, especially in the case of transplantation of segmental grafts. Patient and graft survival might improve by avoiding the identified risk factors.
- Published
- 2000
24. [H-3]thymidine incorporation into whole liver as an alternative to [H-3]thymidine incorporation into DNA as a parameter of cell proliferation in regenerating liver tissue in rats
- Author
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de Jong, KP, Brinker, M, van Veen, M, Daemen, T, Scherphof, GL, Slooff, MJH, Targeted Gynaecologic Oncology (TARGON), Groningen Institute for Organ Transplantation (GIOT), and Guided Treatment in Optimal Selected Cancer Patients (GUTS)
- Subjects
EXPRESSION ,hepatectomy ,HEPATOCELLULAR PROLIFERATION ,METASTASES ,TUMOR-GROWTH ,INHIBITION ,PARTIAL-HEPATECTOMY ,FACTOR-ALPHA ,thymidine ,liver ,EPIDERMAL GROWTH-FACTOR - Abstract
OBJECTIVE: To monitor liver regeneration following partial hepatectomy, liver cell proliferation can be measured by assaying in vivo [H-3]thymidine incorporation into liver cell DNA. We hypothesized that [H-3]thymidine incorporation into whole liver tissue parallels [H-3]thymidine incorporation into liver cell DNA, both in high proliferating and low proliferating liver. STUDY DESIGN: Liver cell proliferation in rats after partial hepatectomy or a sham operation was studied by measuring incorporation of [H-3]thymidine into various fractions of liver tissue on days 1, 2, 3, 4 and 10 after surgery. RESULTS: [H-3]thymidine incorporation into whole with DNA-specific [H-3]thymidine incorporation into regenerating (r > .80, P .69, P
- Published
- 1999
25. Analysis of survival and morbidity after pediatric liver transplantation with full-size and technical-variant grafts
- Author
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Sieders, E, Peeters, PMJG, TenVergert, EM, Bijleveld, CMA, De Jong, KP, Zwaveling, JH, Boersma, GA, Slooff, MJH, Faculteit Medische Wetenschappen/UMCG, Groningen Institute for Organ Transplantation (GIOT), and Guided Treatment in Optimal Selected Cancer Patients (GUTS)
- Subjects
SHORTAGE ,DONOR LIVER ,INFANTS ,CHILDREN ,WAITING-LIST ,HEPATIC TRANSPLANTATION - Abstract
Background To alleviate the shortage of size-matched whole-donor organs, too-large-for-size cadaveric donor grafts are modified by liver resection techniques. These modifications result in technical-variant liver transplantation (TVLTx). Patient and graft survival rates after TVLTx are considered comparable to those after full-size liver transplantation (FSLTx). However, morbidity after TVLTx is often underexposed. The aim of this study was to analyze the results of FSLTk and TVLTx in terms of patient and graft survival rates and morbidity. Methods. A consecutive series of 97 primary and elective pediatric liver transplantations performed in a single center was retrospectively analyzed. Forty-seven children had a FSLTx and 50 a TVLTx (38 reduced-size liver grafts and 12 split-liver grafts). The overall median follow-up period was 3.5 years. Results. There were no differences in patient and graft survival rates between FSLTx and TVLTx. However, after TVLTx there was a significantly higher complication rate (1.42 vs. 0.81 after FSLTx). TVLTx is more hampered by biliary complications (30% vs. 17%), expressed by a higher incidence of cholangitis and leakage of bile. These complications led to a significantly higher incidence of sepsis (44% vs. 19%) and a significantly higher intervention rate (0.40 vs. 1.28) after TVLTx, There was no difference in the incidence of retransplantations between FSLTx and TVLTx. Conclusions. Both FSLTx and TVLTx offer the same prognosis in terms of patient and graft survival rates for children after a primary and elective liver transplantation. However, TVLTx has a higher morbidity.
- Published
- 1999
26. Long-term follow-up after liver transplantation for erythropoietic protoporphyria
- Author
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Meerman, L, Haagsma, EB, Gouw, ASH, Slooff, MJH, Jansen, PLM, and Groningen Institute for Organ Transplantation (GIOT)
- Subjects
ERYTHROHEPATIC PROTOPORPHYRIA ,integumentary system ,liver transplantation ,erythropoietic protoporphyria ,cirrhosis ,FERROCHELATASE GENE ,DEFECT ,INDUCED CHOLESTASIS ,polycyclic compounds ,FAILURE ,HEPATIC-DISEASE ,PERFUSED-RAT-LIVER ,PORPHYRINS ,SKIN FIBROBLASTS - Abstract
Objective Erythropoietic protoporphyria (EPP) is an inherited disorder of haem synthesis, causing excess of protoporphyrin in blood, skin, liver and other organs, Protoporphyrin causes rapidly progressive liver failure in a minority of EPP patients. Long-term follow-up after liver transplantation for EPP is poorly documented, Design Two EPP patients were followed for 7 years after liver transplantation. Porphyrin levels were monitored and serial liver biopsies were taken, Results After transplantation, serum protoporphyrin levels remained elevated. In one patient, long periods with normal liver tests, low protoporphyrin levels and the absence of photosensitivity were followed by episodes of cholestasis and elevated protoporphyrin levels in blood, faeces and liver tissue. These episodes could be managed successfully with blood transfusions and changes in medication, The simultaneous rise of protoporphyrin concentration in both blood and faeces in this patient argues for increased protoporphyrin production as the cause of liver cell injury. The other patient acquired hepatitis B infection during the transplantation. From 3 months onwards she had continuously elevated liver tests, cholestasis, elevated protoporphyrin levels in blood, faeces and liver tissue, and photosensitivity. In this case, cholestasis and impaired protoporphyrin excretion may have played an important role in the persistent liver injury, Sequential liver biopsies of both patients showed various degrees of liver injury related to variations of the hepatic protoporphyrin concentrations. Eight and six months respectively after liver transplantation the livers of both patients showed fibrosis and hepatocellular protoporphyrin accumulation. Conclusions The main cause of liver damage in EPP is overproduction of protoporphyrin in the bone marrow, Liver transplantation must be considered as symptomatic therapy with a high-risk for recurrent disease. Eur J Gastroenterol Hepatol 11:431-438 (C) 1999 Lippincott Williams & Wilkins.
- Published
- 1999
27. Ochrobactrum intermedium infection after liver transplantation
- Author
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Moller, LVM, Arends, JP, Harmsen, HJM, Talens, A, Terpstra, P, Slooff, MJH, Faculteit Medische Wetenschappen/UMCG, and Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI)
- Subjects
ANTHROPI BACTEREMIA ,bacterial infections and mycoses ,GROUP VD - Abstract
A case of bacteremia due to Ochrobactrum intermedium, with concomitant liver abscesses, in an orthotopic liver transplant recipient is presented. Identical microorganisms were isolated from fecal specimens and from an aspirate of a liver abscess that was indicative of invasion of the graft by gastrointestinal spread. 16S DNA sequence analysis of the blood isolate revealed the recovery of the recently proposed new species O. intermedium, closely related to Ochrobactrum anthropi and Brucella spp.
- Published
- 1999
28. Percutaneous drainage of emphysematous cholecystitis associated with pneumoperitoneum
- Author
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Zeebregts, CJ, Wijffels, RTM, de Jong, KP, Peeters, PM, Slooff, MJH, Faculteit Medische Wetenschappen/UMCG, Man, Biomaterials and Microbes (MBM), Vascular Ageing Programme (VAP), Groningen Institute for Organ Transplantation (GIOT), and Guided Treatment in Optimal Selected Cancer Patients (GUTS)
- Subjects
percutaneous drainage ,cholecystostomy ,emphysematous cholecystitis ,pneumoperitoneum ,cholecystectomy - Abstract
Emphysematous cholecystitis, a relatively rare variant of acute cholecystitis, is associated with high morbidity and mortality rates. In the presence of a concomitant pneumoperitoneum, these rates may be considered even higher, approaching those of perforation of the gallbladder. The first choice of treatment in cases presenting with pneumoperitoneum is emergency laparotomy. We performed a staged procedure as a second best alternative. In a 65 year-old female patient, initial percutaneous cholecystostomy with a strict intravenous antibiotics regimen, and subsequent cholecystectomy 6 months, later was carried out with successful outcome. A review of the literature revealed 13 other cases of this combination. Treatment modalities and outcome of these patients are discussed.
- Published
- 1999
29. Gastro-intestinale bloedingen
- Author
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van Buuren, Henk, Mulder, CJJ, Lameris, JS, Bleichrodt, RP, Slooff, MJH, van Lanschot, J.J.B., Gouma, D.J., Schouten, W.R., Tytgat, G.N.J., Jansen, P.L.M., Internal Medicine, and Radiology & Nuclear Medicine
- Published
- 1999
30. Levertransplantatie
- Author
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Metselaar, Herold, Jansen, PLM, Slooff, MJH, Terpstra, OT (Onno), van Lanschot, J.J.B., Gouma, D.J., Schouten, W.R., Tytgat, G.N.J., Jansen, P.L.M., Internal Medicine, and Surgery
- Published
- 1999
31. Donor-specific hyporeactivity after liver transplantation - Prominent decreases in donor-specific cytotoxic T lymphocyte precursor frequencies independent of changes in helper T lymphocyte precursor frequencies or suppressor cell activity
- Author
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de Haan, A, van den Berg, AP, Hepkema, BG, van Dijk, E, Haagsma, EB, The, TH, Slooff, MJH, Lems, SPM, de Leij, LFMH, Prop, J, Faculteit Medische Wetenschappen/UMCG, and Groningen Institute for Organ Transplantation (GIOT)
- Subjects
LIMITING DILUTION ,FUNCTIONAL DELETION ,KIDNEY ,REJECTION ,ALLOGRAFT RECIPIENTS ,RAT ,TOLERANCE INDUCTION ,RESPONSES ,APOPTOSIS - Abstract
Background. The development of immunological donor-specific hyporeactivity may account for the low incidence of chronic rejection after clinical liver transplantation. We investigated whether hyporeactivity commonly develops after liver transplantation by analyzing precursor frequencies of donor-reactive cytotoxic (CTLp) and helper (HTLp) T lymphocytes and mixed lymphocyte culture (MLC) reactivity in liver allograft recipients. We further studied whether CTLp hyporeactivity correlated with changes in donor-specific HTLp frequencies or suppressor cell activity. Methods. CTLp and HTLp frequencies and MLC reactivity against donor and third-party spleen cells were determined in pre- and posttransplantation peripheral blood samples from 18 recipients with good graft function 2 years after transplantation. By mixing posttransplantation samples (with "putative" suppressor cell activity) with pretransplantation samples tin which normal CTL activity with no suppressor cell activity is expected), the presence of suppressor cell activity in peripheral blood was analyzed. Results. Two years after transplantation, all but one (94%) of the recipients had developed CTLp hyporeactivity as evidenced by reduced donor-specific CTLp frequencies. The development of hyporeactivity was not specific for any particular underlying disease. The occurrence of HTL hyporeactivity, however, was less frequent: 38% and 20% of recipients were HTLp and MLC hyporeactive, respectively. Decreases in CTLp frequencies did not correlate with decreased donor-specific HTL function or suppressor cell activity in peripheral blood samples. Conclusions. Donor-specific CTLp hyporeactivity can develop in the majority of liver allograft recipients, irrespective of underlying disease. Donor-specific HTL hyporeactivity, however, occurs infrequently. A reduction in donor-specific CTLp frequencies was found to be independent of changes in donor-specific HTLp or suppressor cell activity, suggesting that other mechanisms (e.g., clonal deletion) are operative in the reduction of donor-specific CTLp after liver transplantation.
- Published
- 1998
32. Routine Doppler ultrasound for the detection of clinically unsuspected vascular complications in the early postoperative phase after orthotopic liver transplantation
- Author
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Kok, T, Slooff, MJH, Thijn, CJP, Peeters, PMJG, Verwer, R, Bijleveld, CMA, van den Berg, AP, Haagsma, EB, Klompmaker, IJ, and Groningen Institute for Organ Transplantation (GIOT)
- Subjects
liver transplantation ,ultrasound ,hepatic artery ,cardiovascular system ,HEPATIC-ARTERY THROMBOSIS ,DUPLEX US ,SONOGRAPHY ,DIAGNOSIS - Abstract
To assess the role of routine Doppler ultrasound in the detection of clinically unsuspected vascular complications in the early postoperative phase after orthotopic liver transplantation (OLT), the findings of 858 routinely performed Doppler ultrasound examinations were analyzed in 268 transplants. At various time intervals after OLT, we encountered 46 abnormal Doppler findings: hepatic artery (thrombosis), portal vein [anastomotic stenosis, (non)occlusive thrombosis or reversed flow], inferior vena cava [anastomotic stenosis with reversed flow, no flow or (non)occlusive thrombosis], and hepatic veins (to-and-fro flow or stenosis with reversed flow) in 14, 20, 9, and 2 transplants, respectively. Most of these abnormal Doppler findings were confirmed by angiography, cavography, or surgery. The positive predictive value for hepatic artery thrombosis (HAT) was 12 out of 14, or 86 %. In the first 2 weeks after OLT, routine Doppler ultrasound revealed 20 of the 46 abnormal findings (43 %). Clinically unsuspected complications of the hepatic artery, portal vein, inferior vena cava, and hepatic veins were found in 9 of the 14 (64 %), 6 of the 20 (30 %), 3 of the 9 (33 %), and 2 of the 2 (100 %) transplants, respectively. The highest incidence nine vascular complications - was found on the 1st day. On each of the remaining days (except for the 2nd and 9th days), one or two vascular complications were detected. HAT was found mainly in the Ist week. Vascular complications developed independently or concomitantly. We conclude that routine Doppler ultrasound is very important for the detection of clinically unsuspected vascular complications, particularly HAT, in the first 2 weeks after OLT. We recommend routine Doppler ultrasound of all hepatic vessels every 3 days in the early postoperative phase after OLT Special attention should be paid to the Ist day.
- Published
- 1998
33. Quantitation of immunosuppression by flow cytometric measurement of the capacity of T cells for interleukin-2 production
- Author
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van den Berg, AP, Twilhaar, WN, Mesander, G, van Son, WJ, van der Bij, W, Klompmaker, IJ, Slooff, MJH, The, TH, de Leij, LHFM, Faculteit Medische Wetenschappen/UMCG, and Groningen Institute for Organ Transplantation (GIOT)
- Subjects
BLOOD ,ANTIGENEMIA ,CHRONIC REJECTION ,CYTOKINES ,CYCLOSPORINE ,LIVER-TRANSPLANTATION ,CALCINEURIN ACTIVITY ,CYTOMEGALOVIRUS-INFECTION ,LEUKOCYTES - Abstract
Background. Methods to quantitate the effects of immunosuppressive drugs on immune reactivity might be helpful for monitoring immunosuppressive treatment. Cyclosporine (CsA) inhibits the induction of cytokine synthesis in T cells, and measurement of interleukin (IL)-2 production might constitute a parameter of this drug's effect. Methods. We determined the percentages of CD4(+) and CD8(+) lymphocytes producing IL-2 upon stimulation by phorbol myristate acetate and calcium ionophore in whole blood culture, using immunostaining of intracytoplasmatic and membrane markers, followed by multiparameter flow cytometry. A total of 38 clinically stable transplant patients on various immunosuppressive protocols were studied. Results. The percentage of CD4(+) T cells producing IL-2 was strongly reduced in patients compared with healthy controls (23% [range, 3-68%] vs. 59.0% [range, 41-70%]; P=0.000035). The percentage of CD4(+) T cells producing IL-2 was negatively correlated with the CSA level (R-c=-0.0821, P=0.00002297) but not with prednisolone or azathioprine doses. Fewer CD8(+) T cells produced IL-2 in transplant patients compared with controls, but the difference failed to reach statistical significance. The percentage of CD8(+) T cells capable of producing IL-2 was inversely correlated to CsA levels (R-c= -0.0375, P=0.0011). Conclusions. These data suggest that the functional effects of CsA in transplant recipients can be quantitatively determined and that the capacity of CD4(+) T cells to produce IL-2 upon stimulation constitutes a functional parameter of CsA effects on the immune system. Prospective studies are required to determine whether this method is useful for clinical monitoring.
- Published
- 1998
34. Liver cell proliferation after partial hepatectomy in rats with liver metastases
- Author
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de Jong, KP, Brouwers, MAM, Huls, GA, Bun, JCAM, Wubbena, AS, Nieuwenhuis, P, Slooff, MJH, Dam, A., Faculteit Medische Wetenschappen/UMCG, Groningen Institute for Organ Transplantation (GIOT), Guided Treatment in Optimal Selected Cancer Patients (GUTS), and Stem Cell Aging Leukemia and Lymphoma (SALL)
- Subjects
HUMAN HEPATOCELLULAR-CARCINOMA ,KUPFFER CELLS ,GROWTH-FACTOR-ALPHA ,TRITIATED-THYMIDINE ,rats, laboratory ,neoplasm metastasis ,hepatectomy ,TUMOR RECURRENCE ,SERUM LEVELS ,RISK-FACTORS ,liver neoplasms, experimental ,NUCLEAR ANTIGEN EXPRESSION ,CURATIVE RESECTION ,IN-VIVO - Abstract
OBJECTIVE: To validate proliferating cell nuclear antigen (PCNA) expression and flow cytometry as proliferation markers in regenerating rat liver containing metastases. STUDY DESIGN: Rats containing colorectal liver metastases were killed at various days after 70% partial hepatectomy or a sham operation. [H-3]thymidine and 5-bromo-2 'deoxyuridine (BrdU) incorporation, PCNA expression and flow cytometry were used to evaluate liver cell proliferation. RESULTS: The assessment of proliferating liver cells by PCNA expression and BrdU incorporation was more reliable than autoradiography. PCNA expression correlated well with BrdU incorporation (r=.68, P=.003) and autoradiography (r=.57, P=.02) in regenerating liver. BrdU incorporation and PCNA expression were higher in hepatectomized rats as compared to sham-operation rats at days 1-4 after hepatectomy. Flow cytometry of propidium-stained nuclei from livers of hepatectomized rats showed a higher proportion of S-phase nuclei as compared to S-phase nuclei in control rats. The correlation coefficients of the number of S-phrase nuclei, BrdU-positive nuclei and PCNA-positive nuclei were .39 (P CONCLUSION: Flow cytometry and PCNA expression are simple and reliable methods of studying proliferation in metastases containing rat liver after partial hepatectomy.
- Published
- 1998
35. Splenic artery aneurysms in liver transplant patients
- Author
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Kobori, L, de Jong, KP, Peeters, PMJG, Klompmaker, IJ, Kok, T, Haagsma, EB, Slooff, MJH, Groningen Institute for Organ Transplantation (GIOT), and Guided Treatment in Optimal Selected Cancer Patients (GUTS)
- Subjects
splenic artery aneurysm ,RUPTURE ,INSTANCE ,orthotopic liver transplantation ,PORTAL-HYPERTENSION ,MANAGEMENT ,portal hypertension ,FETAL SURVIVAL ,cardiovascular diseases ,bleeding ,liver disease - Abstract
Background/Aims: The purpose of the study was to investigate the incidence of Methods: Medical records and the pre- and 1-year postoperative angiograms of 337 liver transplant patients were reviewed to assess the presence and characteristics of these aneurysms. Results: Forty-five patients with aneurysms were identified (13%): 41 cases in 242 adult patients (17%) and four (4%) in 95 children (p Conclusions: The incidence of splenic artery aneurysms in liver transplant patients is 13%, Their are generally multiple and located in the distal third of the splenic artery. The incidence is higher in women and in patients with parenchymal liver disease and portal hypertension, The incidence of rupture was 4%.
- Published
- 1997
36. Poor initial graft function after orthotopic liver transplantation: can it be predicted and does it affect outcome? An analysis of 125 adult primary transplantations
- Author
-
Maring, JK, Klompmaker, IJ, Zwaveling, JH, Kranenburg, K, TenVergert, EM, Slooff, MJH, and University of Groningen
- Subjects
liver transplantation ,primary dysfunction ,ORGAN-TRANSPLANTATION ,graft function ,MARGINAL DONORS ,RISK-FACTORS ,risk factors ,VENOUS BYPASS ,CRITERIA - Abstract
Donor liver shortage is a persistent problem in liver transplantation. A more liberal donor acceptance policy may be a possible solution. However, this might put recipients at risk for initial poor function or even non-function of the graft. Therefore risk factors for initial graft dysfunction should be identified, preferably by using an uniform definition of primary graft dysfunction or non-function. We retrospectively analysed 125 adult liver transplantations in order to identify risk factors for initial poor function and primary non-function. Donor, recipient pretransplant and surgical parameters were evaluated. Since there is no consensus on the criteria of dysfunction we used two definitions known from literature. No risk factors for postoperative dysfunction could be identified for either of the two definition sets. Furthermore, the definition set that included ALAT, prothrombin time and bile production in the first 72 h to identify poor graft function showed no relation with graft or recipient outcome. The other set, using ASAT and prothrombin time, determined from day 2 to day 7, showed that patients with a primary dysfunction had significantly higher morbidity and mortality compared to patients with a well functioning graft. We conclude that initial poor function after liver transplantation remains unpredictable, irrespective of the way it is defined. Moreover, our analysis shows that initial poor function can also develop in recipients that receive 'non-marginal' grafts without prolonged ischemia times. These results may support a more liberal selection of donor livers.
- Published
- 1997
37. Persistent unconjugated hyperbilirubinemia after liver transplantation due to an abnormal bilirubin UDP-glucuronosyltransferase gene promotor sequence in the donor
- Author
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Jansen, PLM, Lems, SPM, Slooff, MJH, Haagsma, EB, and Faculteit Medische Wetenschappen/UMCG
- Subjects
CLEARANCE ,hyperbilirubinemia ,liver transplantation ,CYCLOSPORINE-A ,TATAA box ,DYSFUNCTION GILBERTS SYNDROME ,Gilbert's syndrome ,CRIGLER-NAJJAR SYNDROME ,DIAGNOSIS ,MUTATION ,jaundice ,UDP-glucuronosyltransferase - Abstract
Background/Aims: Gilbert's syndrome is genetically characterized by an extra TA element in the TATAA-box of the promotor region upstream of the bilirubin UDP-glucuronosyltransferase (UGT1A) coding region (Bosma et al. N Engl J Med 1995; 333: 1171-5). Persistent unconjugated hyperbilirubinemia is occasionally observed in liver transplant recipients with an otherwise normal liver function. We postulate that these patients could have received a liver from a donor with the Gilbert's syndrome genotype, Therefore, me investigated the UGT1A-gene TATAA-box in DNA from liver graft donors of jaundiced and non-jaundiced recipients. Methods: DNA was obtained from stored donor lymphocytes and the number of TA elements in the TATAA-box of the UGT1A-gene promotor region was analyzed by polymerase chain-reaction. Results: We observed two liver transplant recipients with persistent unconjugated hyperbilirubinemia. They received liver grafts from donors who were homozygous for an abnormal A(TA)(7)TAA-box in the UGT1A-gene, Four of 10 non-jaundiced recipients received livers from donors who were homozygous for the normal A(TA)(6)TAA-box and six received livers from donors who were heterozygous with a normal A(TA)6TAA-box on one allele and a prolonged A(TA)(7) TAA-box on the other allele. Conclusions: This study shows that liver graft recipients with persistent unconjugated hyperbilirubinemia may have received a liver from a donor with an abnormal TATAA-box in the bilirubin UGT1A-gene promotor region.
- Published
- 1997
38. Low HLA-DR expression on monocytes as a prognostic marker for bacterial sepsis after liver transplantation
- Author
-
VandenBerk, JMM, Oldenbruger, RHJ, VandenBerg, AP, Klompmaker, IJ, Mesander, G, VanSon, WJ, VanderBij, W, Slooff, MJH, The, TH, Faculteit Medische Wetenschappen/UMCG, and Groningen Institute for Organ Transplantation (GIOT)
- Abstract
Background. Low HLA-DR expression on monocytes is associated with an increased risk of infection after surgery or trauma. We determined the value of this parameter as a marker for sepsis after liver transplantation. Methods. The percentage of monocytes expressing HLA-DR was determined by flow cytometry before and after liver transplantation in nine patients. Five lung and 20 kidney transplant recipients served as controls. Results. Bacterial sepsis occurred in 5 of 9 liver transplant patients and 0 of 24 control patients. Monocyte HLA-DR expression decreased 50% in the four liver transplant patients without sepsis. Only 1 of 25 control patients had persistently low monocyte HLA-DR expression. Conclusions. Monitoring of monocyte HLA-DR expression may be helpful in identifying liver transplant patients who have an increased risk of imminent bacterial sepsis.
- Published
- 1997
39. Acute liver failure: Spontaneous recovery or transplantation?
- Author
-
Meerman, L, Zijlstra, JG, Schweizer, JJ, Verwer, R, Slooff, MJH, Haagsma, EB, Faculteit Medische Wetenschappen/UMCG, Critical care, Anesthesiology, Peri-operative and Emergency medicine (CAPE), and Vascular Ageing Programme (VAP)
- Subjects
CONTROLLED TRIAL ,liver transplantation ,FULMINANT HEPATIC-FAILURE ,acute liver failure - Abstract
Background: Decision-making in acute liver failure. Acute liver failure is a disease with multiple organ involvement and a high mortality rate. Conservative management alone will only partly influence the outcome. The option of emergency liver transplantation has greatly improved survival rates, but unables spontaneous recovery. A set of prognostic criteria enables selection of patients who will benefit the most from emergency liver transplantation. Methods: Retrospective review and survey of the Groningen results. Results: Of 52 patients (33 adults and 19 children) admitted for acute liver failure 2 were beyond recovery and died, 9 were treated conservatively and recovered and 41 were listed for emergency liver transplantation because of an estimated survival rate
- Published
- 1997
40. Biliary reconstruction during liver transplantation in patients with primary sclerosing cholangitis
- Author
-
Feith, MP, Klompmaker, IJ, Maring, JK, Peeters, PMJG, vandenBerg, AP, deJong, KP, Haagsma, EB, Gouw, ASH, Slooff, MJH, Groningen Institute for Organ Transplantation (GIOT), and Guided Treatment in Optimal Selected Cancer Patients (GUTS)
- Published
- 1997
41. Incidence, risk factors, and outcome of antithymocyte globulin treatment of steroid-resistant rejection after liver transplantation
- Author
-
Bijleveld, CGE, Klompmaker, IJ, vandenBerg, AP, Gouw, ASH, Hepkema, BG, Haagsma, EB, Slooff, MJH, and Groningen Institute for Organ Transplantation (GIOT)
- Subjects
OKT3 ,TESTS ,steroid-resistant rejection ,THERAPY ,liver transplantation, rejection, ATG - Abstract
We retrospectively analyzed the incidence and outcome of steroid-resistant rejection (SRR) during the first 6 months after OLT in 126 patients receiving triple immunosuppression. A total of 95 patients either did not experience acute rejection at all or had acute rejection that subsided without additional treatment. A total of 31 patients had biopsy-proven acute rejection that required therapy: 18 patients had acute rejection that responded to steroid therapy (steroid-sensitive rejection, SSR); the remaining 13 patients had SRR and received ATG, At the onset of acute rejection, no differences in clinical, biochemical, or immunological parameters were present between patients with SR and SRR. However, the histological grade of acute rejection in the initial biopsy was higher in patients with SRR (P = 0.05), ATG treatment was effective in 10 of the 13 patients and was not associated with an increased incidence of opportunistic infections. Patient and graft survival rates at 2 years were comparable In the three groups. These data show that the incidence of SRR during the first 6 months after OLT is low and that its treatment with ATG is both effective and well tolerated.
- Published
- 1996
42. Adenosine triphosphate-dependent copper transport in human liver
- Author
-
vandenBerg, GJ, Wolters, H, Veld, GI, Slooff, MJH, Heymans, GSA, Kuipers, F, Vonk, RJ, Groningen University Institute for Drug Exploration (GUIDE), and Center for Liver, Digestive and Metabolic Diseases (CLDM)
- Subjects
CANDIDATE GENE ,PLASMA-MEMBRANE VESICLES ,RAT-LIVER ,MENKES DISEASE ,CANALICULAR MEMBRANE ,transport kinetics ,P-TYPE ATPASES ,bile canalicular membrane ,ATP ,copper ,P-type ATPase ,GLUTATHIONE ,WILSON DISEASE GENE ,BILE-SALT ,vesicle ,Wilson disease - Abstract
Background/Aim: The recent cloning and sequencing of the Wilson disease gene indicates that hepatic copper (Cu) transport is mediated by a P-type ATPase. The location of this Cu-transporting protein within the hepatocyte is not known; in view of its proposed function and current concepts of hepatic Cu transport, it may reside in intracellular membranes (endoplasmic reticulum (ER), lysosomes) and/or in the bile canalicular membrane, The objective of this study was to establish characteristics and localization of ATP-dependent Cu transport in human liver. Methods: We have investigated Cu transport in vesicles of human liver plasma membranes showing a gradual increase in enrichment of canalicular domain markers: i.e. basolateral liver plasma membranes (blLPM), a mixed population of basolateral and canalicular (XLPM) and canalicular liver plasma membranes (cLPM). Results: In the presence of ATP (4 mM) and an ATP-regenerating system, uptake of radiolabeled Cu (Cu-64, 10 mu M) into cLPM vesicles and, to a lesser extent, into blLPM and XLPM was clearly stimulated when compared to control AMP values. Initial uptake rates of ATP-dependent Cu transport were 5.6, 7.8 and 13.7 nmol . min(-1). mg(-1) protein for blLPM, XLPM and cLPM, respectively, and showed no relationship with marker enzyme activity of ER and lysosomes (glucose-6-phosphatase and acid-phosphatase, respectively). Leucine aminopeptidase activity, as a marker for the cLPM, significantly correlated with ATP-dependent uptake rates measured in different membrane preparations: r=0.70 (n=9, p Conclusion: This study provides biochemical evidence for the presence of an ATP-dependent Cu transport system in human liver (cCOP), mainly localized at the canalicular domain of the hepatocytic plasma membrane.
- Published
- 1996
43. Comparison of T cell responses in patients with a long-term surviving renal allograft versus a long-term surviving liver allograft - It's a different world
- Author
-
vanTwuyver, E, deHoop, J, tenBerge, RJM, Wilmink, JM, Lems, SPM, vandeBerg, AP, Slooff, MJH, deWaal, LP, and Faculteit Medische Wetenschappen/UMCG
- Subjects
MEDIATED LYMPHOLYSIS ,PRECURSORS ,surgical procedures, operative ,NONREACTIVITY ,HISTOCOMPATIBILITY ,KIDNEY GRAFT-SURVIVAL ,TOLERANCE ,CHIMERISM ,ALLOTRANSPLANTATION ,TRANSPLANT RECIPIENTS ,DONOR - Abstract
The aim of the present study was to analyze whether acquired transplantation tolerance had developed in patients with a long-term surviving rend or liver allograft. Analysis of antidonor cytotoxic T cell precursor frequencies was performed in 31 renal allograft recipients and 9 liver allograft recipients with good graft function 2 years after transplantation. The results demonstrated that, before transplantation, normal antidonor T cell responses were generated in both groups of patients. Two years after transplantation, donor-specific CTL nonresponsiveness had developed in a minority of the renal transplant recipients. Fn contrast, 8 out of 9 liver transplant recipients showed donor-specific mixed lymphocyte culture and CTL nonresponsiveness. These findings indicate that development of donor-specific T cell nonresponsiveness is not a common event after kidney transplantation, whereas liver transplantation seems to induce, at least in vitro, a state of donor-specific T cell nonresponsiveness.
- Published
- 1996
44. Ultrasound and cholangiography for the diagnosis of biliary complications after orthotopic liver transplantation: A comparative study
- Author
-
Kok, T, VanderSluis, A, Klein, JP, VanderJagt, EJ, Peeters, PMJG, Slooff, MJH, Bijleveld, CMA, and Haagsma, EB
- Subjects
SIZE ,liver transplantation ,orthotopic liver transplantation ,TRANS-HEPATIC CHOLANGIOGRAPHY ,sense organs ,SONOGRAPHY ,cholangiography ,skin and connective tissue diseases ,biliary complications - Abstract
The ability of ultrasound to detect biliary obstruction, bile leakage and generalized ductal changes after orthotopic liver transplantation (OLT) was compared to cholangiography. Cholangiography was considered to be the gold standard. Adequate opacification of the biliary tree was achieved in 139 cholangiograms. Biliary obstruction, intermediate or large bile leakage, and generalized ductal changes were diagnosed with cholangiography in 15% (21/139), 14% (20/139), and 16% (22/139), respectively. Normal ultrasound findings could not exclude biliary stricture, generalized ductal changes, or bile leakage, and fluid collections were not correlated with bile leakage. Abnormal ultrasound findings were highly predictive of the cholangiographic diagnosis of biliary obstruction or generalized ductal changes (specificity of 98% and 100%, respectively). An irregular appearance of the bile ducts and increased periductal echogenicity proved to be characteristic features for generalized ductal changes. (C) 1996 John Wiley & Sons, Inc.
- Published
- 1996
45. Primary sclerosing cholangitis and liver transplantation
- Author
-
Klompmaker, IJ, Haagsma, EB, Jansen, PLM, and Slooff, MJH
- Subjects
CHOLANGIOCARCINOMA ,COMPLICATIONS ,surgical procedures, operative ,liver transplantation ,ULCERATIVE-COLITIS ,INFLAMMATORY BOWEL-DISEASE ,PROGNOSTIC VARIABLES ,primary sclerosing cholangitis ,NATURAL-HISTORY ,DYSPLASIA ,CANCER ,digestive system diseases ,ulcerative colitis - Abstract
Primary sclerosing cholangitis is a chronic disease, strongly associated with ulcerative colitis and cholangiocarcinoma. Ulcerative colitis itself does not influence the liver transplant results. However; intensified screening after liver transplantation for carcinoma of the colon may be necessary. Cholangiocarcinoma, although incidentally found in hepatectomy specimens, has a bad prognosis; Initial reports in the literature indicate a far lower survival when liver transplantation is performed for PSC, in comparison to the results achieved in other transplant indications. This might have been due to surgical interventions which nowadays are avoided. Later reports show a better prognosis than the initial ones. We report on the results of liver transplantation for PSC, as indicated in the literature and on the results of the Groningen transplant centre.
- Published
- 1996
46. DOPPLER ULTRASOUND AND ANGIOGRAPHY OF THE VASCULATURE OF THE LIVER IN CHILDREN AFTER ORTHOTOPIC LIVER-TRANSPLANTATION - A PROSPECTIVE-STUDY
- Author
-
KOK, T, PEETERS, PMJG, HEW, JM, MARTIJN, A, KOETSE, HA, BIJLEVELD, CMA, and SLOOFF, MJH
- Subjects
RADIOLOGIC EVALUATION ,DUPLEX SONOGRAPHY ,COMPLICATIONS ,RECIPIENTS ,cardiovascular system ,HEPATIC-ARTERY THROMBOSIS ,FAILURE ,RECONSTRUCTION ,CYCLOSPORINE ERA - Abstract
Despite the availability of Doppler ultrasound, angiography still forms part of the protocol for evaluating children after orthotopic liver transplantation (OLT) at our department. To investigate whether Doppler ultrasound is a reliable method for evaluating the patency of the hepatic artery, portal vein, inferior vena cava, and the anastomotic site of the portal vein in children after OLT, we performed a prospective study in which Doppler ultrasound was compared with angiography in 38 children with 40 transplants (ten examinations on clinical demand and 49 examinations according to protocol). Good correlation was found in relation to demonstrating a patent hepatic artery (sensitivity 96% and specificity 100%). Two false-negative Doppler ultrasound results were attributable to technical difficulties and rejection. For evaluating the patency of the portal vein, Doppler ultrasound agreed with angiography in 58 of the 59 examinations (98%). The one and only false-positive angiography result was explained by inadequate opacification. Doppler ultrasound visualized stenosis of the portal vein three times more often than angiography. In seven children, Doppler ultrasound findings suspicious of pathology of the inferior vena cava were confirmed using cavography or surgery. Doppler ultrasound proved to be a reliable technique for evaluating the patency of the hepatic artery, inferior vena cava, and portal vein and the anastomotic site of the portal vein.
- Published
- 1995
47. GASTRIC TONOMETRY IN ORTHOTOPIC LIVER-TRANSPLANTATION
- Author
-
MARING, JK, ZWAVELING, JH, GIRBES, ARJ, and SLOOFF, MJH
- Published
- 1995
48. HISTOLOGICAL AND BIOCHEMICAL EFFECTS OF CYCLOSPORINE-A WITHDRAWAL FROM A TRIPLE-DRUG REGIMEN AFTER OVER 2 YEARS OF TREATMENT IN LIVER-TRANSPLANT PATIENTS
- Author
-
KLOMPMAKER, IJ, GOUW, ASH, HAAGSMA, EB, SLOOFF, MJH, and Groningen Institute for Organ Transplantation (GIOT)
- Subjects
RENAL-FUNCTION ,RECIPIENTS ,CYCLOSPORINE A WITHDRAWAL ,LIVER HISTOLOGY ,ALLOGRAFT-REJECTION ,LIVER TESTS - Abstract
Cyclosporine A was withdrawn from a triple drug immunosuppressive regimen in 10 clinically and biochemically stable liver transplant patients, This study reports the effects of cyclosporine A withdrawal on liver tests and liver histology. Serum aspartate amino transferase and serum alanine amino transferase values increased significantly, Seven out of ten patients had histological changes after cyclosporine A withdrawal, but not before, These changes were compatible with acute rejection (consistent with rejection) in two patients and grade I also in two patients, including one patient with a second graft. Only two of these patients needed corticosteroid treatment (one consistent with rejection and one grade I rejection). Cyclosporine A treatment was restarted in three patients, because a coexisting osteoporosis prohibited prolonged corticosteroid recycling, Seven patients were able to maintain stable though slightly elevated transaminases without cyclosporine A, with a follow up of median 26 months. Our results suggest that in stable patients cyclosporine A withdrawal can be considered, for instance 2 years after liver transplantation.
- Published
- 1995
49. THE TISSUE HYDRATION STATE IN UW-PRESERVED HUMAN DONOR LIVERS - A CLINICAL-STUDY OF THE RELATION BETWEEN PROTON MAGNETIC-RESONANCE RELAXATION-TIMES, DONOR CONDITION, PRESERVATION PROCEDURE, AND EARLY GRAFT FUNCTION
- Author
-
WOLF, RFE, DENBUTTER, G, KAMMAN, RL, DEKETH, HP, SLUTTER, WJ, SLOOFF, MJH, and Faculteit Medische Wetenschappen/UMCG
- Subjects
T2 ,T1 ,VOLUME ,RAT-LIVER ,RELAXOMETRY ,TEMPERATURE ,NMR ,BRAIN-EDEMA - Abstract
To determine the relation between tissue hydration state-as indicated by tissue proton magnetic resonance relaxation times-in UW-preserved human donor livers and viability parameters of the donor and early graft function, ''ex vivo'' magnetic resonance relaxometry was performed with a clinical MR imaging system. Relaxometric data were obtained from MR images in which signal intensities were directly proportional to T-1 and T-2. Forty three subsequently transplanted livers and five discarded livers were studied. The donor serum concentrations of direct and total bilirubin had a positive correlation with T-1 (P
- Published
- 1994
50. IS THERE RECURRENCE OF PRIMARY BILIARY-CIRRHOSIS AFTER LIVER-TRANSPLANTATION - A CLINICOPATHOLOGICAL STUDY IN LONG-TERM SURVIVORS
- Author
-
GOUW, ASH, HAAGSMA, EB, MANNS, M, KLOMPMAKER, IJ, SLOOFF, MJH, GERBER, MA, and Groningen Institute for Organ Transplantation (GIOT)
- Subjects
IDENTIFICATION ,T-CELLS ,PRIMARY BILIARY CIRRHOSIS ,CYCLOSPORINE ,LIVER TRANSPLANTATION ,ANTIMITOCHONDRIAL ANTIBODIES ,DISEASE RECURRENCE ,RECURRENCE ,ANTIGENS ,SUBTYPES - Abstract
Liver transplantation has been accepted as a successful therapeutic tool for irreversible liver diseases such as primary biliary cirrhosis. However, removal of the diseased liver may not eliminate this autoimmune disease, and recurrence of primary biliary cirrhosis in the liver graft has been reported as early as within the first posttransplant year. We studied whether or not primary biliary cirrhosis recurs after liver transplantation in follow-up biopsies of 19 primary biliary cirrhosis patients. Biopsies of 14 non-primary biliary cirrhosis patients served as controls. The median follow-up period was 5 years (range 1-11 years). Both groups of patients were selected according to strict criteria which excluded pre- and posttransplant diseases which could mimic primary biliary cirrhosis. The follow-up biopsies were taken according to a protocol at yearly intervals. Established histologic criteria for primary biliary cirrhosis were assessed semi-quantitatively in 119 biopsies in a coded fashion. A longitudinal study was performed after decoding the biopsies, to document the course of morphological changes in time per patient. In addition to data on liver tests and immunosuppression, antimitochondrial antibodies including the primary biliary cirrhosis specific subtypes (anti-PDH-E2 and BCKD-E2) were determined in freeze-stored serum samples. The biopsies showed a striking concordance between the primary biliary cirrhosis and non-primary biliary cirrhosis groups and few overt histologic abnormalities. There was no significant difference in liver-test results and immunosuppression. Overall anti-mitochondrial antibodies remained present in decreased titers. We found portal granulomas as well as mild bile-duct damage in the 3rd year biopsies of two primary biliary cirrhosis patients, but no abnormal liver tests or clinical symptoms. These findings were not conclusive for primary biliary cirrhosis and subsequent biopsies did not show diagnostic features of primary biliary cirrhosis. Based on these results, we conclude that there were no distinctive histologic nor serologic findings for recurrent primary biliary cirrhosis. In the liver transplant patient population of this study, with a posttransplantation follow-up period of 11 years, no cases of recurrent primary biliary cirrhosis were diagnosed. (C) Journal of Hepatology.
- Published
- 1994
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