Omgaan met schaarste

Schaarste, het thema van mijn oratie, is één van de centrale begrippen in de economie. Volgens Van Dale is schaarste de omstandigheid dat iets in onvoldoende hoeveelheid beschikbaar is. Dagelijks ervaren we de schaarste aan een bepaald goed. Er zijn te weinig betaalbare huizen voor jonge mensen en te weinig leraren in het onderwijs. Soms is er een tekort aan bedden op de afdeling of onvoldoende MRI capaciteit. Maar ook het ontbreken van tijd en geld om die wereldreis te maken met je geliefde is een vorm van schaarste. Kortom schaarste hoort bij het leven…….. en bij de dood. Want die is vaak heel nabij als door een tekort aan organen de transplantatie van een nier, lever of hart niet mogelijk is. Schaarste dwingt tot het maken van keuzes. Schaarste stimuleert ook het zoeken naar creatieve oplossingen. Soms is schaarste de reden voor revolutie en misdaad, aldus de Griekse fi losoof Aristoteles. In het tweede gedeelte van mijn oratie zal ik aantonen dat de zorg voor ernstig zieke leverpatiënten soms tekortschiet door schaarste aan donororganen, nog ontbrekende wetenschappelijke kennis, schaarste aan hepatologen en schaarste aan transplantatiechirurgen. Dat zijn geen natuurverschijnselen die ons overkomen, maar problemen die of met politieke wil of met voldoende onderzoeksgeld zijn op te lossen. Ik zal daarvoor een aantal suggesties doen. Maar eerst zal ik in het kort de geschiedenis van de levertransplantatie (LTx) schetsen. Uiteraard kijk ik daarbij ook speciaal naar Rotterdam

Diagnosis and prevention of cytomegalovirus infection after organtransplantation

Although the introduction of cyclosporin A (GsA) as the main immunosuppressive agent seems to have influenced the incidence and severity of CMV disease in a positive way, the reported incidence of clinical overt CMV infection is still 2 - 23 % and 1 - 3 % of the transplant recipients die from CMV infection. It is therefore obvious that this virus remains a major pathogen after organ transplantation. DIAGNOSIS OF CMV INFECTION When CMV disease is diagnosed, reduction of immunosuppressive therapy will markedly decrease morbidity and mortality without affecting graft survival. Moreover, antiviral therapy with either ganciclovir or foscarnet can be considered in patients with severe symptomatic disease. This management of symptomatic CMV infections (tapering of immunosuppressive drugs and j or antiviral therapy) makes rapid and early diagnosis necessary. Although the measurement of virus specific antibodies is sensitive, the long physiological response-time of antibody synthesis (one to two weeks ) during active CMV infection makes this method inappropriate for rapid and early diagnosis. Moreover, in patients with immunosuppression antibody synthesis can be impaired. Detection of a morphological cytopathological effect (CPE) of CMV in tissue cultures has the same disadvantage. The method takes long time and is sometimes impossible due to bacterial contaminated specimens or coinfection with the herpes simplex virus. In this thesis two methods for rapid and early diagnosis of CMV infection are described. First, we compared in our patients the results obtained by a low-speed centrifugation assay in combination with immunofluorescence by a monoclonal antibody against early antigen of CMV with the results from the conventional tissue culture method. Second, an indirect method for detection of active CMV infection is described. In the peripheral blood of renal transplant recipients mononuclear subpopulations were monitored with monoclonal antibodies before, during and after CMV infection

Incidence of osteonecrosis after renal transplantation

The incidence of osteonecrosis was 24% in 248 patients who had received 262 kidney transplants 1971-1982. However, based only on patients at risk, i.e. alive with functioning transplants, the incidence at 1, 3 and 6 years was found to be 13, 27 and 36%; after six years no new cases were found. the relative increase in body-weight at 180 days was predictive as regards risk for osteonecrosis, while the cumulative dose of steroids was not. This suggests that individual sensitivity to steroids rather than the absolute cumulative dose is involved in the development of osteonecrosis

Fibrinolysis during liver transplantation is enhanced by using solvent/detergent virus-inactivated plasma (ESDEP)

After the introduction of solvent/detergent-treated plasma (ESDEP) in our hospital, an increased incidence of hyperfibrinolysis was observed (75% vs 29%; P = 0.005) compared with the use of fresh frozen plasma for liver transplantation. To clarify this increased incidence, intraoperative plasma samples of patients treated with fresh frozen plasma or ESDEP were analyzed in a retrospective observational study. During the anhepatic phase, plasma levels of D-dimer (6.58 vs 1.53 microg/mL; P = 0.02) and fibrinogen degradation products (60 vs 23 mg/L; P = 0.018) were significantly higher in patients treated with ESDEP. After reperfusion, differences increased to 23.5 vs 4.7 microg/mL (D-dimer, P = 0.002) and 161 vs 57 mg/L (fibrinogen degradation products, P = 0.001). The amount of plasma received per packed red blood cell concentrate, clotting tests, and levels of individual clotting factors did not show significant differences between the groups. alpha(2)-Antiplasmin levels, however, were significantly lower in patients receiving ESDEP during the anhepatic phase (0.37 vs 0.65 IU/mL; P < 0.001) and after reperfusion (0.27 vs 0.58 IU/mL; P = 0.001). Analysis of alpha(2)-antiplasmin levels in ESDEP alone showed a reduction to 0.28 IU/mL (normal >0.95 IU/mL) because of the solvent/detergent process. Therapeutic consequences for the use of ESDEP in orthotopic liver transplantation are discussed in view of an increased incidence of hyperfibrinolysis caused by reduced levels of alpha(2)-antiplasmin in the solvent/detergent-treated plasma. IMPLICATIONS: The use of solvent/detergent virus-inactivated plasma is of increasing importance in the prevention of human immunodeficiency virus and hepatitis C virus transmission. Since the use of this plasma during orthotopic liver transplantation has increased, the incidence of hyperfibrinolysis was observed. Clotting analysis of the patients revealed small alpha(2)-antiplasmin concentrations because of the solvent/detergent process