The first two cases of living donor liver transplantation using dual grafts in Europe.

The major limitation in adult-to-adult living donor liver transplantation (LDLT) is an adequate graft size with special regard to the safety of the donor. Only 20% of the evaluated donors are suitable to donate the right liver, depending mainly on the critical remnant liver volume. We report 2 cases of adult-to-adult LDLT using dual grafts. In the first case we implanted a left lateral lobe together with a left lobe; in the second case we used a left lateral and a right lobe. Dual graft LDLT solves the problem of graft-size insufficiency and avoids critical right lobectomy in the donor. This procedure can be safely performed and opens up the possibility of LDLT to even more families in the Western world.     

Evaluation potenzieller Leberlebendspender

INTRODUCTION: The increasing shortage of cadaveric organs makes living-related liver transplantation a more and more important option. Safety for the donor has the highest priority, and therefore detailed and thorough evaluation is needed. MATERIALS AND METHODS: All potential donors who had been evaluated at our center from January 2001 to March 2002 ( n=100) were included in a retrospective study to analyse the qualitative, logistical, and economic aspects of the evaluation. RESULTS: Seventy-three percent of the potential donors were found to be unsuitable for living donation during the evaluation process. The main reasons were: uncompatible blood group, availability of cadaveric transplant by Eurotransplant, steatosis of more than 10% of hepatocytes in liver biopsy, insufficient liver volume, and psychosocial reasons. The expenditure for all scheduled investigations was 4,469 euro for a complete evaluation. CONCLUSION: While on the one hand, high standards of the evaluation process must be guaranteed, insufficient reimbursement on the other should not lead centers to reduce either quantity or quality of necessary examinations entered in the evaluation protocol.     

Clinical reactivation after liver transplantation with an unusual minor strain of hepatitis B virus in an occult carrier.

Hepatitis B virus (HBV) DNA is detectable in a number of liver transplant candidates who are negative for hepatitis B surface antigen (HBsAg). After liver transplantation (LT), such patients may have molecular and/or serologic evidence of HBV replication. However, clinical disease from reactivation of occult HBV infection after LT has not been described. We report a patient who underwent LT for cryptogenic cirrhosis and had to be retransplanted twice for hepatic artery thrombosis. The patient was negative for HBsAg and positive for anti-hepatitis B core (HBc) and anti-HBs before all LT procedures and developed acute hepatitis B shortly after receiving the third graft. The HBV strain isolated at that time exhibited an unusual in frame insertion of a CAG motif within the HBV polymerase (HBV(INS+)). HBV(INS+) was detected retrospectively as a minor species in pretransplantation sera and the explanted native liver by insertion-specific polymerase chain reaction. This case in an occult HBV carrier shows that clinically apparent, endogenous reinfection of the graft may occur with minor HBV variants that are not detectable in pretransplantation samples by standard diagnostic procedures. This has implications for the analysis of sources of acute hepatitis B in patients after LT and possibly for consideration of antiviral prophylaxis in anti-HBc/anti-HBs/HBV DNA-positive patients.     

X-chromosomal gebundener Hydrozephalus (HSAS) Eine Erkrankung aus der Gruppe der CRASH-Syndrome

Hintergrund.  

Unter CRASH-Syndrom wird eine Gruppe von X-chromosomal vererbten Erkrankungen zusammengefasst, die eine Mutation im L1CAM-Gen vorweisen und nach dem Akronym CRASH folgende Symptome vorweisen k?nnen: Corpus-callosum-Hypoplasie, Retardierung, adduzierte Daumen, spastische Paraplegie und Hydrozephalus. Eine Erkrankung aus dieser Reihe ist der X-chromosomal gebundene Hydrozephalus, erstmals beschrieben von Bickers und Adams 1949 als Hydrozephalus mit ?quaduktstenose (HSAS).     

Kontraktur,Zuckung und Calcium

Zusammenfassung Es wurden Überlegungen und Experimente darüber angestellt, ob und wie das Ca bei der Kontraktur und bei der Zuckung von Skeletmuskeln beteiligt ist. Vor allem interessierte die Frage, ob es verschieden gebundenes bzw. lokalisiertes Ca in der Muskelfaser gibt, das unterschiedlich in Funktion treten kann (Kontraktur- bzw. Zuckungs-Ca). Im einzelnen konnten folgende Befunde erhoben werden:1. Wird ein Ganzmuskel (Sartorius) in Ca-freie Ringer-Lösung gebracht, so sinkt das Membranpotential seiner Fasern an der Oberfläche (und wahrscheinlich auch in der Tiefe) relativ langsam und wenig ab.Man kann daraus schließen, daß offenbar noch sehr lange etwas Ca von innen nach außen wandert, das ausreicht, einen großen Teil der Fasern vor stärkerer Depolarisation zu schützen. Trotzdem verliert der Muskel seine Kontrakturfähigkeit. Dies bedeutet, daß während der Ca-Verarmung eines Ganzmuskels die zur Kontrakturunfähigkeit führende Insuffizienz der elektromechanischen Kopplung schon einsetzt, bevor die Muskelfasern im Durchschnitt stärker depolarisiert und deswegen unerregbar geworden sind. Inwieweit diese am Ganzmuskel erhobenen Befunde auch für die isolierte Einzelfaser gelten, muß noch offenbleiben. Diesbezügliche eigene und fremde Untersuchungsergebnisse werden diskutiert.2. Es wird gezeigt, daß das die Kontraktur ermöglichende Ca leicht gebunden und leicht beweglich ist (Kontraktur-Ca). Dies trifft besonders für den Calciummechanismus tonischer Fasern zu. Sie können z.B. leicht Ca aus dem umgebenden Medium aufnehmen und dadurch ihre Kontrakturfähigkeit steigern. Auch Zuckungsfasern können aus einer Careichen Lösung viel Ca aufnehmen, doch wird ihre Kontrakturfähigkeit dadurch im Vergleich zu den tonischen Fasern viel weniger gesteigert. Das Ca wird hier offenbar in der Zelle rasch und so gebunden, daß es selbst durch den Trigger der depolarisierenden Kontraktursubstanz (z. B. KCl) nicht ausreichend mobilisiert werden kann.3. Dieses (im sarkoplasmatischen Reticulum?) fester gebundene Ca wird bei der Ca-Verarmung (Ca-freies Außenmedium) nur schwer und langsam abgegeben. Es scheint für die Zuckung gebraucht zu werden. Denn Zuckungen sind noch möglich, wenn im Verlauf der Ca-Verarmung keine Kontrakturen (und Nachkontrakturen) mehr auslösbar sind, d. h. das locker gebundene Ca der Zelle stark reduziert ist.4. Der Grund für die rasche Ermüdbarkeit Ca-verarmter Muskeln bei wiederholter elektrischer Reizung (Einzelzuckungen und Tetani) liegt weniger in einer Insuffizienz der mechanischen Ankopplung als in einer fortschreitenden Depolarisation der Muskelfasern infolge verlangsamter bzw. ungenügender Repolarisation.5. Es wird folgende Arbeitshypothese aufgestellt:Die Auslösung der Zuckung und der Kontraktur folgt einem verschiedenen Zeitfaktor. Nur der schnelle Trigger des Aktionspotentials vermag das im Zellinnern fester gebundene Ca für die Zuckung freizusetzen, das in einer Folgereaktion rasch wieder gebunden wird. Dagegen mobilisiert die langsame Depolarisation durch Kontrakturstoffe gerade das locker gebundene Ca, das beim Vorhandensein geeigneter Wege bzw. Transportmechanismen (worüber vorzugsweise die tonischen Muskelfasern verfügen) ins Faserinnere diffundieren und die Fibrillen nacheinander aktivieren kann.6. Die kontrakturauslösende Wirkung von H⁺- und Phosphat^–––-Ionen auch bei Ca-verarmten Muskeln beruht wahrscheinlich auf ihrer Fähigkeit, fest gebundenes Ca freizusetzen.

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Summary Questions were raised and experiments were done to see if and how Calcium is associated with twitches and contractures of skeletal muscles. The main question that interested us was are there different bound or localized Ca fractions in a muscle fibre, which perform different functions (contracture- or twitch-calcium)? The following facts were shown:1. If a whole muscle (sartorius muscle) was brought into a calciumfree Ringer's solution, then the membrane potential on its surface (and probably in the depth of the fibres also) would sink comparatively slowly and comparatively little.From this fact one can say that apparently for a long time sufficient Ca diffuses from the inside to the outside fibres of the muscle to protect these fibres form a stronger depolarization. Even though the muscle looses its ability to make contractures. This means that the insufficiency of the electromechanical-coupling mechanism (causing the inability for contractures) starts during the Ca-deprivation of a whole muscle before a stronger depolarization and inexcitability of the fibres can be observed on the average. How much one can compare this reaction on the whole muscle with a reaction on a single muscle fibre is still unanswered. Our own experimental results and other experimental results are discussed.2. It is shown that the Ca-fraction that is responsible for contractures is only lightly bound and very lightly mobile (contracture-Ca). This applies especially to the calcium mechanism of tonic muscles. These muscles can, for example, absorb calcium very easily from the surrounding medium and through this they can increase their contracture ability.The twitch fibres can also take up much calcium from a calcium-rich surrounding, but their contracture ability is much less than those of the tonic type. Apparently the Ca is bound fast and in such a way by the cell that even if the cell is depolarized by a contracture substance (for example KCl), it doesn't respond well because the calcium can't be mobilized fast enough.3. This more solidly bound Ca (in the sarcoplasmatic reticulum?) is given off only slowly and with much resistance to the outside by calcium loss (surroundings are free of calcium). This calcium seems to be used for the twitches, because twitsche are still possible during the time of Ca-loss when one can't cause any contractures (or after-contractures), that is, when the loosly bound calcium is reduced.4. The reason that a calcium-deficient muscle gets fatigued so fast after continued electrical irritation (single twitches and tetanus) is not to be found so much in an insufficiency of the mechanical coupling as in an continuing depolarization of the muscle fibres following a slowed up or insufficient repolarization.5. The following working hypothesis is suggested:The causing mechanisms of the twitch and contracture are governed by different time factors. Only the fast trigger of the action potential has the ability to set free the stronger bound calcium in the interior of the cell, which in a following reaction would be very quickly bound again. On the other side, slow depolarization with contracture substances mobilizes just that loosly bound calcium, which in the presence of suitable ways of transportation mechanisms (whereby we have merely here the tonic muscles) diffuses into the centre of the fibre and can activate the fibriles one after another.6. That H⁺- and PO ₄ ^––– -ions, also in calcium deficient muscles can cause contractures is probably based upon the ability of the muscles to set free strongly bound calcium.

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Mit 8 Textabbildungen

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Mit Unterstützung der Deutschen Forschungsgemeinschaft.     

Interaction of hepatocytes and pancreatic islets cotransplanted in polymeric matrices

Heterotopic hepatocyte transplantation (HcTx) in polymeric matrices may become an alternative to liver transplantation for metabolic disorders. Hepatotrophic stimulation by means of a portocaval shunt operation is an established, but invasive, procedure used to optimize hepatocyte engraftment in matrices. We evaluated hepatocyte and pancreatic islet cotransplantation (ICT) as an alternative noninvasive approach to hepatotrophic stimulation. Lewis rats served as donors and recipients. Hepatocytes and islets were isolated using collagenase digestion and seeded into polyvinylalcohol matrices. HcTx and ICT were compared with HcTx plus portocaval shunt and HcTx without stimulation. Matrices were investigated at 1, 3, and 6 months after implantation: the test methods applied were trichrome staining, PAS, immunohistochemistry for insulin, glucagon and incorporated BrdU, and in situ hybridization for albumin RNA. Hepatocytes expressed albumin RNA and formed conglomerates without atypias in all animals. ICT and portocaval shunting increased the number of hepatocytes and BrdU uptake. Alpha cells migrated into the islet-surrounding hepatocytes, whereas beta cells remained immobile. It is concluded that ICT and portocaval shunting supported engraftment of hepatocytes in polymeric matrices equally well. ICT did not interfere with recipient glucose metabolism and did not induce hyperproliferative premalignant foci within the transplanted hepatocytes. The technique is an attractive approach to hepatotrophic stimulation of bioartificial liver equivalents. Received: 10 February 1999 / Accepted: 22 April 1999