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H J Metselaar

Publications and source records attributed to H J Metselaar.

At least 37 records · Page 2Linked to original sources

Aspergillus osteomyelitis after liver transplantation: conservative or surgical treatment?

We report on a liver transplant recipient who developed coxarthritis and lumbar spondylodiscitis due to Aspergillus flavus. He was treated with high-dose liposomal amphotericin B for 2 months followed by itraconazole. Because of intractable pain and severe, irreversible damage of the left hip, a Girdlestone resection was performed. The spondylodiscitis was treated successfully with anti-fungal agents only, which indicates that, in the absence of neurological impairment, good clinical outcome can be achieved without surgery. This case demonstrates that surgical therapy, which is often proclaimed as unavoidable for the treatment of Aspergillus osteomyelitis, should be considered in particular in the case of intolerable pain due to irreversible joint damage or involvement of vital organs.

Adult↗

Efficacy of influenza vaccination in adult liver transplant recipients.

To assess the efficacy of influenza vaccination in immunocompromised adult liver transplant (LTx) recipients, the serum antibody responses of 61 of these patients and 35 liver cirrhosis patients with those of 45 of their healthy spouses were compared, after one and two vaccinations with a commercial trivalent subunit influenza vaccine. In addition, virus-specific proliferative T-cell responses were measured in LTx recipients and their healthy spouses. In all three study groups, significant rises in geometric mean antibody titers were observed for all three antigens after one vaccination. These titers did not continue to increase significantly after the second vaccination in patients with cirrhosis and control subjects but did rise for LTx recipients. The overall antibody response to all three influenza virus strains proved to be significantly lower in the LTx recipients than in the group of healthy subjects after both one and two vaccinations. More than 68% of the LTx recipients developed hemagglutination-inhibiting serum antibody titers >/=40 against all three vaccine strains after the first vaccination and more than 80% after the second vaccination. These findings correlated with the T-cell responses determined for the group of LTx recipients and healthy control individuals. Testing of the respective serum samples against influenza virus A/Sydney/5/97, which circulated in the 1997-1998 influenza season and showed a considerable mismatch with the vaccine strain A/Nanchang/933/95, indicated that such a mismatch may have significant consequences for vaccine efficacy, especially for LTx recipients. Collectively the data show that LTx recipients can be vaccinated effectively against influenza despite immunosuppressive therapy. A two-dose vaccination regimen improved vaccination efficacy in LTx recipients. Whether transplant patients generally benefit from a two-dose vaccination regimen should be evaluated further.

Adult↗

[Successful pregnancy after liver transplantation].

Two women aged 32 and 30 years became pregnant following orthotopic liver transplantation. The time intervals between transplantation and conception were 9 years and 9 months, respectively. Both women had immunosuppressive prophylaxis. The course of both pregnancies was uneventful; there were no signs or symptoms of graft rejection. At term, both women were delivered vaginally of female infants, weighing 2510 g (2.3rd-5th percentile) and 3200 g (50th-75th percentile), respectively. The second woman had a normal postpartum period while the first one needed blood transfusion for anaemia due to postpartum haemorrhage. From the literature to date it is concluded that apart from an increased likelihood of opportunistic infections, hypertension, diabetes mellitus, osteoporosis, impaired renal function and foetal growth restriction the outcome of pregnancy in women after a liver transplantation is generally favourable. However, the possible long-term effects of medical treatment on maternal and infant health are unknown.

Adult↗

[Acute hepatocytic necrosis during ketoconazole therapy for treatment of onychomycosis. National Foundation for Registry and Evaluation of Adverse Effects].

The imidazole derivative ketoconazole is approved in the Netherlands for treatment of local and systemic fungal infections. Despite the risk of major hepatic damage, this antimycotic drug is still being used in daily practice for the oral treatment of patients with onychomycosis. Since April 1986, 18 cases of relatively severe hepatic damage in the Netherlands were ascribed to the oral use of ketoconazole for the treatment of onychomycosis, skin infection or vaginal candidiasis. Given the potential risk for the patients concerned, ketoconazole should no longer be prescribed for relatively mild cosmetic disorders such as onychomycosis.

Adolescent↗

Increased intragraft IL-15 mRNA expression after liver transplantation.

To study T-cell/macrophage interactions at the molecular level in clinical allograft rejection, we measured intragraft mRNA expression of the T-cell derived cytokine IL-2 and the macrophage derived chemokine IL-15, a novel cytokine associated with T-cell activation, in post-transplant liver biopsies (n = 33) and in non-transplanted control liver tissue by reverse transcriptase-polymerase chain reaction (RT-PCR). We analyzed biopsies without evidence of rejection (n = 12), with spontaneously resolving histological rejection (n = 10), or with histological rejection accompanied with clinical rejection (n = 11) defined by rising serum bilirubin and aspartate amino transaminase levels. IL-15 mRNA expression was present in the majority of post-transplant liver biopsies (91%, 30/33) and was significantly upregulated as compared with non-transplanted liver tissue (p = 0.005). However, the increased intragraft IL-15 mRNA level was not indicative for rejection. In contrast to intragraft IL-15 mRNA expression, IL-2 mRNA transcription was measured in the minority of the post-transplant liver biopsies (15%, 5/33) and not detectable in control specimens. In addition, IL-2 mRNA was almost specifically measured in rejection biopsies concurrent with graft dysfunction (36%, 4/11 versus 1/22 without clinical rejection; p = 0.03). No relation between intragraft IL-2 and IL-15 mRNA expression was found. The IL-15 mRNA expression levels were not higher in the IL-2 negative rejections compared with those in IL-2 positive rejections. To conclude, in contrast to IL-2, the function of IL-15 in T-cell mediated rejection remains unclear. The overall high IL-15 mRNA levels in sites of immune responses suggests that the macrophage-derived mediator IL-15 is involved in a constant flow of T-cells from the circulation into the graft.

Biopsy↗

Intragraft IL-4 mRNA expression is associated with down-regulation of liver graft rejection.

The mechanism underlying spontaneously resolving allograft rejection following clinical liver transplantation is unidentified. In this process, immunoregulatory T helper (Th)-2 cytokines like IL-4, often identified with down-regulation of the Th1-dependent (IL-2) cell-mediated response, might play a significant but unknown role. For this reason, we analyzed mRNA expression by reverse transcriptase-polymerase chain reaction (RT-PCR) in 57 biopsies derived from 19 recipients. Specimens included biopsies without evidence of rejection (n = 36), biopsies with histological evidence of rejection (n = 10) not followed by clinical signs of graft rejection, and biopsies with histological rejection that were accompanied with clinical rejection (n = 11), defined by rising serum bilirubin and aspartate amino transaminase (ASAT) levels. Intragraft IL-4 mRNA expression significantly correlated with spontaneously resolving rejections. In 70% (7/10) of these biopsies, IL-4 mRNA was detectable, while only 19% (7/36) of the biopsies without signs of rejection (p < 0.01; Fisher's exact test) and 18% (2/11) of the rejection biopsies concurrent with graft dysfunction expressed the IL-4 gene (p = 0.03). In contrast, IL-2 mRNA expression was not detectable in biopsies derived from the spontaneously resolving rejections. None (0/10) of these samples expressed the IL-2 gene, which was not significantly different from the proportion of biopsies transcribing the IL-2 gene in the absence of rejection (11%, 4/36). IL-2 mRNA expression was found more often in biopsies associated with graft dysfunction (36%, 4/11). These results show that IL-4, in contrast to IL-2 mRNA expression, is associated with spontaneously resolving liver rejection. This suggests that Th2 cells down-regulate the Th1-dependent cell-mediated immune response after clinical liver transplantation.

Aspartate Aminotransferases↗

[Criteria for and results of liver transplantation in patients with acute liver insufficiency].

OBJECTIVE: Evaluation of the results of emergency liver transplantation in patients with acute liver failure. DESIGN: Analysis of 25 patients with acute liver failure. SETTING: University Hospital Rotterdam Dijkzigt. METHOD: Twenty-five patients with acute liver failure were admitted to the Intensive Care Unit in January 1989-May 1993. Patients were selected for emergency liver transplantation according to the Clichy criteria (presence of confusion or coma and factor V activity less than 20-30%). RESULTS: Liver transplantation was indicated in 17 patients and performed in 13. The 1-year survival rate in patients with a liver transplant was 85%. Four patients with an indication for liver transplantation, but who could not be transplanted died. All 8 patients without an indication for emergency liver transplantation survived. CONCLUSION: Survival after liver transplantation for acute hepatic failure is now about 80%; the Clichy criteria appear to be helpful in selecting patients with acute hepatic failure for liver transplantation.

Adolescent↗

Intravascular coagulation in liver transplantation--is it present or not? A comparison between orthotopic and heterotopic liver transplantation.

UNLABELLED: It is still not clear whether disseminated intravascular coagulation (DIC) contributes to the hemostatic disturbances in orthotopic liver transplantation (OLT). Theoretically the lack of hepatic clearance of procoagulant factors during the anhepatic period and the release of thromboplastic material from the graft might trigger DIC. During heterotopic liver transplantation (HLT) the host liver is left in situ and procoagulant factors may still be cleared; DIC, if present, may not occur until after reperfusion. The aim of the present study was to gain more insight into the underlying mechanism of the coagulation changes during liver transplantation by comparison of OLT and HLT. Thrombin-antithrombin-III complexes (TAT), and indicator of thrombin generation, fibrin degradation products (FbDP) and routine clotting times were assayed in 12 OLTs, 18 HLTs and in a control group of 10 partial hepatic resections (PHR). TAT increased dramatically after reperfusion to 136 micrograms/l in OLT and to 94 micrograms/l in HLT (p n.s.). In contrast, FbDP levels increased only in OLT, to a maximum of 13.8 micrograms/ml. Routine clotting times changed mildly and similarly in both OLT and HLT. CONCLUSIONS: Graft reperfusion triggers excessive thrombin formation, but there are no other signs of subsequent DIC. Any thrombin formed is probably rapidly inhibited by antithrombin-III. The rise in FbDP during OLT is the result of increased fibrinolysis, which occurred only in OLT and not in HLT.

Antithrombin III↗

The appearance of donor heparin in the recipient after reperfusion of a liver graft.

The release of heparin has been mentioned as one of the causes of hypocoagulability after reperfusion of the liver graft. It has been ascribed to endogenous heparin released from the donor liver or to exogenous heparin in the preservation fluid that is released into the recipient after sequestration into the graft during preservation. The aim of this study was to investigate whether systemic administration of heparin to the donor before the hepatectomy contributes to the appearance of heparin in the recipient after reperfusion. We studied 20 patients undergoing an auxiliary heterotopic liver transplantation; 15 donors had received heparin immediately before circulation arrest (median 300 IU/kg body weight), but 5 had not. The thrombin time (TT), activated partial thromboplastin time (aPTT), and heparin neutralization test were determined at several intervals during the transplantation.

Adolescent↗

Long-term application of human polyclonal hepatitis-B immunoglobulin to prevent hepatic allograft infection. A review of the literature and presentation of five cases.

Liver transplantation has evolved as the therapy of choice in end-stage liver disease. However, liver transplantation for viral liver disease is associated with recurrence of viral hepatitis in the graft. In this paper we discuss the mechanisms of liver cell damage, the clinical impact of recurrent infection and the use of hepatitis-B-specific immunoglobulin (HBIg) to prevent recurrent infection in the allograft. In addition, we propose an HBIg schedule tailored to each individual patient. Based on the excellent survival results published for acute hepatic failure and chronic liver failure with latent hepatitis B virus (HBV) or hepatitis delta infection, we think that no contraindication exists for liver transplantation in these cases. For patients with active viral replication, liver transplantation should only be considered within a scientific frame to prevent reinfection of the allograft.

Chronic Disease↗

Increased tissue-type plasminogen activator activity in orthotopic but not heterotopic liver transplantation: the role of the anhepatic period.

The major cause of the increased tissue-type plasminogen activator activity during orthotopic liver transplantation is still unclear. Both the lack of hepatic clearance of tissue-type plasminogen activator in the anhepatic period and increased endothelial release from the graft on reperfusion have been proposed as the major causes. Heterotopic liver transplantation avoids the resection of the host liver and is a useful model to help differentiate between these two possibilities. In this study the fibrinolytic system was evaluated in 10 orthotopic liver transplantations, 18 heterotopic liver transplantations and a control group of 10 partial hepatic resections. A marked increment in tissue-type plasminogen activator activity, from 0.2 to 5.2 IU/ml (p less than 0.02), was observed during the anhepatic period of orthotopic liver transplantation, which rapidly normalized after reperfusion. In contrast, tissue-type plasminogen activator activity levels remained normal in heterotopic liver transplantation and partial hepatic resections. In orthotopic liver transplantation and in heterotopic liver transplantation no increase occurred in tissue-type plasminogen activator activity after reperfusion. The first venous hepatic outflow after reperfusion did not contain elevated tissue-type plasminogen activator activity levels. Plasma degradation products of fibrin and fibrinogen increased during the anhepatic period of orthotopic liver transplantation (from 2.60 to 8.80 micrograms/ml [p less than 0.008] and from 0.40 to 1.60 micrograms/ml [p less than 0.04], respectively) and remained elevated thereafter. In heterotopic liver transplantation and partial hepatic resections these levels remained low. In conclusion, the lack of hepatic clearance during the anhepatic period is probably the most important factor in the evolution of increased tissue-type plasminogen activator activity during orthotopic liver transplantation.

Blood Transfusion↗

Donor directed cytotoxicity of cardiac graft infiltrating cells during cytomegalovirus infection.

We investigated whether cytomegalovirus (CMV) infection had an effect on donor directed cytotoxicity of cardiac graft infiltrating cells. The group we studied comprised 89 heart transplant recipients. Thirty eight showed signs of CMV infection, and in 27 of them cytolytic activity of biopsy-derived cultures could be tested during the infection. Fifty-one patients had never had CMV infection, and they were used as the control group. Eight patients had a primary, and 19 a secondary infection. We found that during CMV infection, both primary and secondary, a significantly higher proportion of the biopsy-derived cultures showed cytotoxicity against donor antigens (P < 0.01 when compared to the control group). In secondary infections, this was only due to an increase in donor class I directed cytotoxicity, while in primary infections a significant increase of class II directed cytotoxicity was also found (P < 0.005 when compared to secondary infection).

Cell Culture Techniques↗

Increased fibrinolysis in orthotopic but not in heterotopic liver transplantation: the role of the anhepatic phase.

The major cause of increased tissue-type plasminogen activator (t-PA) activity during orthotopic liver transplantation (OLT) is still unclear. Both lack of hepatic clearance of t-PA in the anhepatic period and/or increased endothelial release from the graft upon reperfusion have been suggested. Heterotopic liver transplantation (HLT) avoids resection of the host liver and is therefore a useful model to differentiate these two possibilities. The fibrinolytic system was evaluated in ten patients with OLT and in 18 patients with HLT. A marked increment in t-PA activity was observed during the anhepatic period of OLT, which rapidly normalized after reperfusion. In contrast t-PA activity levels remained normal in HLT. As a reflection of the increased t-PA activity fibrin degradation products were markedly elevated during OLT and plasminogen and alpha2-antiplasmin decreased simultaneously during the anhepatic period. In conclusion, the lack of hepatic clearance during the anhepatic period is the most important factor in the evolution of increased t-PA activity during OLT.

Fibrinolysis↗

[Favorable results of auxiliary heterotopic liver transplantation in patients with end-stage chronic liver insufficiency].

Auxiliary heterotopic liver transplantation (HLT), which avoids removal of the host liver, may improve the results of liver transplantation in patients with end-stage chronic liver disease. However, the results of HLT have so far been disappointing. In 1986 a program of HLT was started in the University Hospital Rotterdam-Dijkzigt. Eighteen patients with chronic liver failure underwent HLT. Twelve out of 18 (67%) patients were discharged 25 days after transplantation with normal liver function. Six patients died within 3 months after operation due to septic causes. Three months after transplantation ascites was no longer detectable and oesophageal varices had disappeared in all surviving recipients of HLT. The actuarial 3 and 12 months survival rate was 67%. Hepatitis B virus reinfection was seen in all patients. In two patients cirrhosis of the graft developed within one year. These data suggest that HLT in patients with chronic liver failure gives long-term metabolic support and adequate decompression of portal system, and is associated with a morbidity and mortality comparable to that of orthotopic liver transplantation.

Adult↗