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Biomedical subjects

M J Slooff

Publications and source records attributed to M J Slooff.

At least 91 records · Page 5Linked to original sources

Changes in portal hemodynamics and acute rejection in the first 2 weeks after orthotopic liver transplantation. A prospective Doppler ultrasound study.

RATIONALE AND OBJECTIVES: To analyze changes in Doppler ultrasound variables of the portal vein in relation to liver biopsy findings, the authors performed a prospective study of 316 Doppler ultrasound examinations in the first 2 weeks after orthotopic liver transplantation on 23 patients. METHODS: Recordings were obtained daily from the portal vein (diameter, maximum velocity, and flow). 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: In our series of 23 patients, acute rejection was diagnosed by liver biopsy in nine of them (39%). Changes in portal vein diameter, maximum velocity, and flow did not correlate consistently with liver biopsy findings, due to a multifactorial origin. Changes in portal hemodynamics were observed in patients with hepatic artery thrombosis, portal vein stenosis, acute rejection, and sepsis. CONCLUSIONS: Although routine screening using Doppler ultrasound proved to be useful for the determination of rapid changes in portal hemodynamics within a short time, serial Doppler ultrasound examinations were not helpful in predicting acute rejection.

Acute Disease↗

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↗

[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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

Characterization of transport in isolated human hepatocytes. A study with the bile acid taurocholic acid, the uncharged ouabain and the organic cations vecuronium and rocuronium.

The uptake and efflux of three categories of substrates were measured in isolated human hepatocytes and compared to those in rat hepatocytes. In addition, the extent to which the in vitro experiments quantitatively reflect liver function in vivo in both species was investigated. The anionic bile acid taurocholic acid was taken up by isolated human hepatocytes at a considerably lower rate than observed in isolated rat hepatocytes. Taurocholic acid uptake both in human hepatocytes and in liver plasma membrane vesicles showed sodium dependency. The uptake rate of taurocholic acid in isolated hepatocytes of both species was quantitatively compatible with the reported liver clearance of the bile acid in vivo. Ouabain uptake rate in isolated human hepatocytes was lower than in rat hepatocytes. This species difference was in accordance with pharmacokinetic studies in vivo on hepatic clearance of ouabain in man and rat. Uptake of vecuronium into human hepatocytes was about a factor of 10 lower than that in rat hepatocytes. Uptake into and efflux from human hepatocytes was comparable for the two short acting muscle relaxants vecuronium and rocuronium. Since distribution to the liver is considered to be a major factor in termination of action of vecuronium and rocuronium these observations were in line with the human pharmacokinetic profiles. In conclusion, the uptake rate of the studied model compounds in human hepatocytes appeared to be lower than that in rat hepatocytes. These observed transport rates reflected the relative hepatic transport rates observed in these species in the intact organism, but the absolute values in both species for some substrates may have been somewhat lower than calculated from in vivo data. It is concluded that transport studies in isolated hepatocytes are suitable for comparative drug transport studies, but are less precise in the prediction of quantitative membrane transport.

Androstanols↗

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.

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 T1 and T2. 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 T1 (P < 0.05 and P < 0.01, respectively). Sequential measurements in 7 livers demonstrated a firm time relation between the cold storage time and the length of the relaxation times. As cold storage time lengthened, T1 and T2 shortened. T1 of the donor liver showed a significant negative correlation with recipient ASAT and ALAT values on days 1, 2, and 3 after transplantation. T1 in the discarded group was significantly higher than T1 in the accepted group. T2 was not different in the two groups. It is concluded that in UW-preserved human donor livers, the tissue hydration state, as indicated by the tissue MR relaxation times, is largely independent of the clinical condition of the organ donor and the preservation procedure. An optimum tissue hydration state, in UW-preserved donors liver might have protective properties against parenchymal damage, although the clinical consequences appear to be of minor importance. The capacity of relaxometry as a discriminative instrument to accept or to discard donor livers is poor.

Adenosine↗

Ex vivo magnetic resonance imaging of pretransplant human donor liver. Clinical experience in 66 cases.

Magnetic resonance imaging (MRI) was performed on 66 cold-stored human donor livers. Spin echo images were obtained with a clinical whole body MRI system. Various parenchymal and vascular abnormalities were found. An unexpected finding was the abundant presence of intrahepatic air. Although the majority of parenchymal abnormalities that were found would not have precluded transplantation, the rationale of pretransplant MRI was to prevent the introduction of unidentified pathology into the recipient. Guided by the MR images, lesions in the isolated organ can be easily located for biopsy and resection. Unnecessary or inadequate therapeutic interventions after transplantation can thus be avoided. In addition, the visualization of the hepatic veins with their confluence appears to be useful in split-liver procedures.

Humans↗