PubMed Health⌕ Search

Biomedical subjects

M J Slooff

Publications and source records attributed to M J Slooff.

At least 19 recordsLinked to original sources
PubMed1996

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.

The aim of the present study was to analyze whether acquired transplantation tolerance had developed in patients with a long-term surviving renal 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. In 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.

Cytotoxicity, Immunologic↗
PubMed1996

Tissue pH in cold-stored human donor livers preserved in University of Wisconsin solution. A noninavasive clinical study with 31P-magnetic resonance spectroscopy.

It is not known whether the tissue acidosis that accompanies cold storage is the beginning of irreversible cell injury, ultimately leading to cell death, or whether it is a natural "protective" mechanism for cells to survive hypoxic periods. To answer this question, the tissue pH of 45 cold-stored human donor livers preserved in University of Wisconsin solution (UW) was assessed shortly before implantation using noninvasive 31P magnetic resonance spectroscopy. We conclude that tissue pH during cold storage may be partly dependent upon hepatic glycogen stores and donor age. The wide range of tissue pH values that was observed at the time of implantation does not result in significant effects on cellular damage after transplantation. This indicates that tissue pH is not a major determinant for the viability of UW solution-preserved human donor livers, as indicated by postoperative hepatocellular damage and liver synthesis function. The membrane stabilizing and buffering capacity of UW solution appears to protect liver viability against tissue acidosis. Our results also indicate that liver tissue pH can be lower than has been previously assumed in the literature without significant adverse effects on liver viability.

Adenosine↗
PubMed1996

Bile acids suppress the secretion of very-low-density lipoprotein by human hepatocytes in primary culture.

The existence of a relationship between bile acid and triacylglycerol metabolism in humans has been established, but the underlying mechanism and its physiological relevance have remained unclear. We have studied the effects of bile acids on the secretion of very-low-density lipoprotein (VLDL)-associated triacylglycerol, using [3H]glycerol labeling technique, and apolipoprotein B (apoB) in human hepatocytes in primary culture. Human hepatocytes secrete nascent VLDL with an average diameter of about 40 nm. Lipid composition of the particles resembles that reported for plasma VLDL, with the exception of a markedly lower cholesterylester content. In 24-hour cultured human hepatocytes, physiological (i.e., portal) concentrations of taurocholic acid (10 to 200 mumol/L) suppressed [3H]triacylglycerol secretion dose dependently. The degree of inhibition highly correlated (r = .87, P < .01) with taurocholic acid content of the cells of different preparations (n = 7). ApoB secretion was inhibited by taurocholic acid to a similar extent as [3H]triacylglycerol secretion (r = .93, P < .01). Lipid composition of secreted VLDL particles did not change during taurocholic acid-induced suppression. No effects on intracellular apoB, [3H]triacylglycerol, triacylglycerol, and cholesterol mass were observed, nor did taurocholic acid affect protein synthesis, albumin secretion, or lactate dehydrogenase (LDH) release. Cellular cholesteryl ester (CHE) mass, however, was markedly reduced. Our results show that bile acids strongly interfere with the assembly or secretion of VLDL particles by human hepatocytes, suggesting a physiological function of the enterohepatic circulation of bile acids in the regulation of postprandial serum lipid levels.

Adult↗
PubMed1996

Doppler ultrasound of the hepatic artery and vein performed daily in the first two weeks after orthotopic liver transplantation. Useful for the diagnosis of acute rejection?

RATIONALE AND OBJECTIVES: To analyze changes in Doppler ultrasound variables in relation to liver biopsy findings for the diagnosis of acute rejection after orthotopic liver transplantation (OLT), the authors performed in a prospective study 316 Doppler ultrasound examinations in the first 2 weeks after OLT on 23 patients. METHODS: Recordings were obtained daily from the hepatic artery (resistive index [RI]) and hepatic vein (damping index [DI]). Correlations were explored between the Doppler ultrasound findings and histologic data. The chi-square test was used to analyze differences in Doppler ultrasound variables in patients with and without acute rejection. RESULTS: Serial Doppler ultrasound examinations showed a significant increase in the RI in 11 of 22 patients (50%); the 23rd patient was excluded because of hepatic artery thrombosis. Despite an agreement in 15 of 22 patients (68%) no statistically significant correlation could be found (positive predictive value 6/11 = 55%; negative predictive value 9/11 = 82%; chi-square = 3.14; P > 0.05). A significant increase in the DI was observed in 14 of 23 patients (61%). However, no statistically significant correlation could be found as well with this parameter (positive predictive value 6/14 = 43%; negative predictive value 6/9 = 67%; chi-square = 0.00; P > 0.05). CONCLUSION: Serial Doppler ultrasound examinations were not helpful in predicting acute rejection.

Acute Disease↗
PubMed1996

Evidence for an increased rate of bacterial infections in liver transplant patients with cytomegalovirus infection.

It has been reported that cytomegalovirus (CMV) infections increase the susceptibility of transplant patients for other opportunistic infections. Most of these studies date back from a time when CMV infection was difficult to diagnose and antiviral treatment not available. We therefore analyzed CMV-related morbidity after OLT in 111 consecutive patients. CMV monitoring was done weekly using the antigenemia assay, a quantitative marker of the viral load, in addition to serology. CMV infection occurred in 66/95 (69%) evaluable patients. Antigenemia was detected in 94% of them. The number of CMV antigen-positive cells was helpful to monitor the course of infection and differentiate CMV disease from other complications. CMV infection was symptomatic in 48/66 (73%) patients. Mild disease occurred in 30 patients, and severe constitutional symptoms or organ involvement in 18. No patient died as a direct result of CMV infection, but mortality between day 30 and 180 tended to be higher in CMV-infected patients (15 vs. 0%, p < 0.1). CMV infection was associated with a 2.45-fold higher incidence of major infections between day 30 and 180 after OLT (p < 0.05). Most of these infections were caused by gram-positive cocci. We conclude that CMV not only causes substantial morbidity, but also increases the risk of bacterial infections.

Adolescent↗
PubMed1995

[Good results with liver resection for colorectal liver metastases].

OBJECTIVE: Evaluation of the results of partial liver resections in patients with colorectal carcinoma with liver metastases. DESIGN: Retrospective descriptive study. SETTING: Groningen University Hospital, the Netherlands. METHODS: Between January 1987 and December 1994, 62 patients were referred for liver resection for metastases of colorectal carcinoma (Dukes C 57%, Dukes B 40%, Dukes A 3%). Twenty-five of these patients were women and 37 men, ranging in age from 28 to 77 years (median 57 years). RESULTS: Liver resection was not performed in 29 patients because of unresectability of the liver lesions (n = 18), lymph node metastases found during laparotomy (4), multiple lung metastases (3) and other reasons (4). Thirty-three patients underwent potentially curative resection without mortality and with complications in 25%. Five-year survival and five-year disease-free survival were 51% and 22% respectively. Patients with a solitary metastasis showed a trend towards a longer survival than patients with two or more liver metastases because of a significantly higher rate of recurrent disease in the latter group of patients (p < 0.05). Nineteen patients (58%) developed recurrent disease between 3 to 44 months (median 15 months): relapse of the primary tumor (n = 7; 37%), recurrent liver metastases (6; 32%) lung metastases (5; 26%), and bone metastasis (I). CONCLUSIONS: Partial liver resections for metastatic disease of colorectal carcinoma can be performed without mortality and with acceptable morbidity. In case of solitary metastasis, liver resection is the therapy of choice as this is the only chance of long-term disease-free survival.

Adult↗
PubMed1995

Venous air embolism, preservation/reperfusion injury, and the presence of intravascular air collection in human donor livers: a retrospective clinical study.

In human liver transplantation, air embolism is seldom encountered after graft reperfusion. Nevertheless, despite adequate flushing and clamping routines, air emboli have been reported in transesophageal echocardiography (TEE) studies performed during the reperfusion phase. We retrospectively investigated whether air in the donor liver -- as observed with pretransplant magnetic resonance imaging (MRI) -- resulted in clinical air embolism or contributed to preservation/reperfusion injury. Clinical air embolism was assessed by intraoperative hemodynamics and end-tidal CO2 monitoring. Preservation/reperfusion injury was assessed in postoperative biochemical measurements. The outcomes were compared between patients receiving livers containing significant intrahepatic air and patients receiving livers without intrahepatic air. Forty-three livers were studied, seven which had major intrahepatic air and ten of which had no evidence of air collections. Twenty-six livers showed minor amounts of air and were excluded from further study. One patient who received a liver that did not contain intrahepatic air had clinical evidence of air embolism. Clinical air embolism did not appear to be associated with the presence of significant intrahepatic air based upon pretransplant MRI. Intrahepatic air did not seem to affect the amount of preservation/reperfusion injury. Our data indicate that air bubbles in the portal and arterial branches are absorbed during reperfusion and that the majority of intrahepatic air is effectively removed by the specific flushing routines.

Embolism, Air↗
PubMed1995

Reduced size liver transplantation, split liver transplantation, and living related liver transplantation in relation to the donor organ shortage.

Because of the shortage of cadaveric donors, three techniques of partial liver grafting have been developed. These techniques are placed in perspective in relation to the organ shortage. Reduced size liver transplantation (RSLTx) is widely used and has results comparable to those from whole liver grafting. However, this technique, while benefitting pediatric patients, reduces the adult donor liver pool. It also makes inefficient use of an available adult donor liver. In split liver transplantation (SPLTx), the whole liver is used after bipartition for two recipients. The results are comparable to those of RSLTx. The problem with SPLTx is that it is a very demanding technique applied only in centers with extensive experience with liver resection and reduction. Living related liver transplantation (LRLTx) yields excellent results; however, it places an otherwise healthy person at risk. It is argued that instead of performing risky operations on healthy persons, the health authorities should take specific measures to alleviate the organ shortage. In the meantime, SPLTx should be developed further because of its optimal use of donor tissue. As for LRLTx, its excellent results and the present shortage of size-matched pediatric liver donors justify its use, at least for now.

Adult↗
PubMed1995

Doppler ultrasound and angiography of the vasculature of the liver in children after orthotopic liver transplantation: a prospective study.

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.

Adolescent↗
PubMed1995

Increasing cyanosis after total cavopulmonary connection treated by banding a separate liver vein.

An increasing right-to-left shunt after a total cavopulmonary connection was treated by banding the separate liver vein. As a variation on a fenestrated total cavopulmonary connection, this liver vein was not connected with the intercaval tunnel. After a few days, the shunt increased to an unacceptable level. This was treated by banding the liver vein, which was connected with the right-sided atrium and turned out to be only part of the venous drainage of the liver.

Child, Preschool↗
PubMed1995

Histological and biochemical effects of cyclosporine A withdrawal from a triple drug regimen after over 2 years of treatment in liver transplant patients.

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.

Adult↗
PubMed1995

Magnetic resonance venography in liver bipartition procedures using preservation solution as contrast agent.

To evaluate whether the hepatic veins can be visualized with a rapid noninvasive technique, and if so, whether the obtained images could be helpful in the preparation of split liver grafts for transplantation, six cold stored human donor livers were investigated with magnetic resonance imaging (MRI). The hepatic vein branches and their confluence were clearly visualized. Anatomic variations of the middle hepatic vein with consequences for the choice of the transection plane could be demonstrated. Furthermore, unexpected vascular abnormalities were detected. From these preliminary results it is concluded that visualization of the hepatic veins can be helpful in determining the feasibility of the bipartition procedure and the choice of the transection plane. A potential wide application of this fast and noninvasive technique is possible.

Adenosine↗
PubMed1995

Ex vivo MRI in extracorporeal liver surgery.

Extracorporeal resection of hepatic tumors that were considered inoperable in the past is now possible in selected cases. Such procedures require high-quality preoperative images for the exact delineation of the tumor extent and for an optimal planning of the line of parenchymal division. In-vivo CT and MRI can not always depict the tumor adequately. In such cases, ex-vivo MRI may be a useful additional technique. It combines a high spatial resolution with the best possible soft tissue contrast, as was learned from previous studies on donor livers destined for transplantation. Ex-vivo MRI favours both a sufficiently radical resection as well as sufficient hepatic functional reserve to be present for reimplantation. A case history is reported together with details on the technical procedure.

Adenocarcinoma↗
PubMed1995

Differences in propionate-induced inhibition of cholesterol and triacylglycerol synthesis between human and rat hepatocytes in primary culture.

Propionate is a short-chain fatty acid formed in the colon and supposedly involved in the cholesterol-lowering effect of soluble fibre. To explore the underlying mechanism(s) of this fibre action, we have used human hepatocytes in primary culture to study the effects of propionate on hepatic lipid synthesis. Initial experiments with mevalonate and mevinolin, a competitive inhibitor of hydroxymethylglutaryl (HMG)-CoA reductase (EC 1.1.1.88) were performed to evaluate basic regulatory mechanisms in these cells; results were compared with those obtained with rat hepatocytes. Incubation for 24 h with mevalonate caused a similar, concentration-dependent inhibition of [14C]acetate incorporation into cholesterol in human and rat hepatocytes. Likewise, mevinolin (100 mumol/l) inhibited the formation of cholesterol from radiolabelled acetate by about 80% in cells from both species. Propionate inhibited cholesterol as well as triacylglycerol synthesis from [14C]acetate with a similar concentration-dependency in rat hepatocytes. Fifty percent inhibition was obtained at a propionate concentration of only 0.1 mmol/l. This propionate-induced inhibition was not affected by a 100-fold excess of unlabelled acetate. Human hepatocytes were much less susceptible in this respect: propionate concentrations of 10-20 mmol/l were required to obtain similar inhibitory effects in these cells, i.e. values greatly exceeding reported portal propionate concentrations in humans. The results suggest the existence of differences in the regulation of hepatic cholesterol (and triacylglycerol) synthesis between human and rat liver cells. These results do not support the hypothesis that the fibre-induced decrease in plasma cholesterol concentration in man is mediated by a direct effect of propionate on hepatic cholesterol synthesis.

Acetates↗
PubMed1995

Hepatitis B-associated liver cirrhosis as an indication for liver transplantation.

Fourteen HBsAg-positive patients received a liver transplant in Groningen. Two were HBeAg-positive and 12 HBeAg-negative. No anti-HBs immunoglobulin was given at the time. Both HBeAg-positive and 9 of 12 of the HBeAg-negative patients became HBsAg-positive again after transplantation. Virus titers were tested in eight patients. Two HBeAg-negative patients were HBV-DNA-negative at transplantation and are still HBV-DNA-negative one-and-half-years after transplantation, both by the branched DNA hybridization technique and by PCR (cut-off values 0.7 x 10(6) and 10(3) HBV genomes/ml, respectively). One patient who had a low HBV-DNA titer at transplantation remained PCR-positive thereafter, but became HBsAg-negative. All other patients were HBV-DNA-positive and had a recurrence that rapidly led to high HBV titers. The liver histology was characterized by fibrosis and cirrhosis, centrilobular cholestasis and high expression of HBsAg and HBcAg, but with little inflammatory infiltrate. We conclude from these results that without anti-HBs immunoglobulin prophylaxis there is a high rate of HBV recurrence after transplantation. The current policy is that patients who test negative in the HBV-DNA dot-blot assay (< 10(7) genomes/ml) are transplantation candidates and are treated with high-dose anti-HBs immunoglobulin after transplantation. HBV-DNA-positive patients (> 10(7) genomes/ml) remain poor candidates for liver transplantation, even with anti-HBs immunoprophylaxis.

DNA, Viral↗
PubMed1995

The effect of partial hepatectomy on tumor growth in rats: in vivo and in vitro studies.

Residual tumor in the remnant liver after partial hepatectomy (PH) for colorectal liver metastases is a serious clinical problem. This fact is reflected by the high number of recurrences after potentially curative liver resections. Liver regeneration, it appears, might influence the growth of remaining micrometastases in the liver. Using rats, we demonstrated enhancement of growth of a syngeneic colon carcinoma (CC 531) in the remnant liver after 70% PH. Fourteen days after PH, tumor weights in the liver were twice as high as those of sham-operated rats. This difference in tumor weight was not found in extrahepatic tumors. In vitro experiments did not show stimulation of cultured CC 531 cells by portal or systemic serum withdrawn 24 hours or 14 days after hepatectomy as compared with sera obtained after sham operation. Co-cultures of CC 531 cells and hepatocytes (in ratios of 1:10 or 1:1) demonstrated a higher 3H-thymidine incorporation than was the case in separately cultured cells. In co-cultures, bromodeoxyuridine (BrdU) incorporation in DNA was found primarily in CC 531 cells and rarely in hepatocytes. Cell density appeared to be of influence on 3H-thymidine incorporation in co-cultures. Hepatocytes were found to have a stimulating effect on CC 531 cells in low-density cultures, whereas high-density cultures exhibited an inhibiting effect after a culture time of 120 hours. These results show that, depending on cell density in co-cultures, a paracrine stimulating influence of hepatocytes on this type of colon carcinoma cells (CC 531) might be responsible for the increased tumor growth in vivo.

Animals↗