Management of acute rejection 2 years after allogeneic vascularized knee joint transplantation.
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Arthroplasty, Replacement, Knee↗
Biomedical subjects
M Diefenbeck
Publications and source records attributed to M Diefenbeck.
[Treatment of MRSA infection in orthopedic surgery].
INTRODUCTION: Infection with methicillin-resistant Staphylococcus aureus (MRSA) remains a major challenge both therapeutically and hygienically. METHODS: Between January 2000 and January 2002, 27 patients with MRSA infections were treated and evaluated in a prospective clinical study. For effective wound management, operative revisions were performed every 3rd day. Following debridement, the wounds were vacuum sealed and specific i.v. antibiotics were administered. Wound closure was performed if three consecutive wound samples submitted for bacterial culture remained negative. RESULTS: All patients with MRSA infections were treated successfully until signs of infection disappeared and bacterial cultures were negative. An average of 7.3 operations per patient was required to eradicate MRSA infection. Follow-up of patients revealed recurrence of infection in four patients. CONCLUSION: Prevention of further spreading and successful treatment of MRSA infections in reconstructive orthopedic surgery is possible with appropriate surgical and hygienic concepts. In almost every second patient complex revision procedures were required.
Adolescent↗
Monitoring of microhemodynamic changes during ex vivo xenogeneic liver perfusion using intravital microscopy.
The main targets of xenogeneic rejection mechanisms are the endothelial cells of the graft. Their activation and the consequent alteration of the organ's microcirculation lead to the destruction of the xenograft. Microhemodynamic changes occurring during this process are still poorly characterized. The aim of this study was to analyze the microcirculation during xenogeneic ex vivo hemoperfusion of rat livers and to monitor the impact of treatment strategies using intravital fluorescence microscopy. In contrast to the isogeneic control group, blood flow almost completely stopped within the first minutes of xenoperfusion. Simultaneously, perfusion pressure increased and bile production was reduced. Acetylsalicylate (Aspisol) and the platelet-activating factor antagonist WEB 2170 improved the microcirculation and function of the xenoperfused liver. The combination showed a synergistic effect. After apheresis of preformed xenogeneic antibodies, the parameters measured were comparable with those seen in isogeneic experiments. Complement degradation with cobra venom factor revealed a minor improvement in perfusion. A rapid, extensive, and irreversible leukocyte accumulation in terminal portal vessels was observed in all xenogeneic experiments. Blood counts of the perfusate confirmed the early trapping of leukocytes and platelets in the xenoperfused liver, indicating nonimmunological, cellular involvement in this rejection process.
Animals↗
Xenogeneic rejection mechanisms shown by intravital microscopy.
The importance of this model is that it showed exactly where in the organ the xenogeneic damage occurred. The liver received the blood mainly via portal veins, which merge with the pulsatile arterioles in the Disse spaces. This periportal area is followed by the sinusoids and ends in the central or postsinusoidal vein. IVM enables us to differentiate between perfused and unperfused sinusoids and to calculate the ratio. Not all sinusoids are perfused at any time. It appears that 5% to 10% are unperfused. During xenoperfusion, only 65% of sinusoids show blood flow after a perfusion of 12 minutes. This is less than in hemorrhagic shock. Only the combined platelet inhibitors and apheresis resulted in remarkable improvement. The calculation of an index indicates the improvement of acinar perfusion. Thrombocytes and leukocytes remain, however, in the liver. In conclusion, the model used to analyze the dynamics of microvascular liver perfusion and sinusoidal perfusion is suitable for such investigations in a xenogeneic model. It has no major side effects, either on the perfusing blood or on the liver, as proved in the isogeneic control group. The important finding in our eyes is that the perfusion failure begins in the periportal fields, where the blood enters the foreign microvasculature and where the leukocytes first come in contact with the foreign endothelium. All previous manipulations had only a minor impact on this contact of cells with the foreign endothelium. The study indicates that the early events of xenogeneic hyperacute rejection are of unspecific character and involve leukocytes and thrombocytes to a major degree, thus being responsible for the dramatic decrease in the microcirculation in xenogeneic livers.
Animals↗
Intravital microscopic investigation of xenogeneic microcirculation and impact of complement depletion by cobra venom factor.
Discordant xenografts are hyperacutely rejected within minutes. Disturbances in the microcirculation are considered to be the central mechanisms of hyperacute xenogeneic rejection (HXR). In this study intravital fluorescence microscopy was applied to investigate the dynamics of microcirculatory alterations in a setting in which HXR was inhibited by complement (C) depletion. Blood flow was measured as rat livers were perfused with isogeneic rat or xenogeneic human blood to assess the pattern of either physiological isogeneic hemoperfusion or in the course of HXR. Next, the complement system of the perfusate was inactivated by cobra venom factor (CVF) in order to inhibit HXR. Liver sinusoids of the isogeneic group were homogeneously perfused (sinusoidal perfusion rate 93.6+/-0.3%), whereas in the xenogeneic group the sinusoidal perfusion rate dropped to 67.1+/-3%. The perfusion in the periportal zone of an acinus was significantly lower ( 59.0+/-3.3%) than in the pericentral zone (76.2+/-3.1%). Treatment with CVF improved the sinusoidal perfusion to a value of 85.6+/-2.3%, physiological perfusion, however could not be reached. In contrast to the isogeneic group, massive white blood cell (WBC) and platelet accumulation was found in the xenogeneic group, especially in the terminal portal vessels and in the periportal zone of liver acini. WBC and platelet counts show that the adherence of these cells appears rapidly in the first 5 min after reperfusion as firm adherence. CVF was not able to inhibit WBC and platelet accumulation, indicating that WBC endothelial interactions do not require an intact complement system. Bile flow, a parameter of liver function, decreased only slightly during isogeneic perfusion. The addition of CVF to the rat blood reduced the bile flow to one half of the untreated isogeneic flow, indicating a hepatotoxic side-effect of CVF. In xenogeneic perfusion the bile flow dropped to 62.6% and with the addition of CVF to 37.5% in the first 15 min after reperfusion. The bile flow of the CVF treated groups recovered during the perfusion but could not reach isogeneic values.
Acute Disease↗
Organs from animals for man.
In the following review some of the problems of xenotransplantation shall be discussed, based on the few experimental data available so far and on reports in the literature describing investigations which may be of importance for xenotransplantation. The impact of gravity on the upright posture of man versus almost all other mammals, the dysfunction between enzymes and hormones in different species and the lack of interactions between interleukins, cytokines and vasoactive substances will be taken into consideration. The question must be asked whether different levels of carrier molecules or serum proteins play a role in the physiological network. Even though the development of transgenic animals or other imaginative manipulations may lead to the acceptance of any type of xenografted organ, it has to be established for how long the products of the xenografts are able to act in the multifactorial orchestra. We are far from understanding xenogeneic molecular mechanisms involved in toxicity, necrosis and apoptosis or even reperfusion injury and ischemia in addition to the immediate mechanisms of the hyperacute xenogeneic rejection. Here, cell adhesion, blood clotting and vasomotion collide and bring micro- and macrocirculation to a standstill. All types of xenogeneic immunological mechanisms studied so far were found to have a more serious impact than those seen in allogeneic transplantation. In addition we are now only beginning to understand that so-called immunological parameters in allogeneic mechanisms act also in a true physiological manner in the xenogeneic situation. These molecular mechanisms occur behind the curtain of hyperacute, accelerated, acute or chronic xenograft rejection of which only some folds have been lifted to allow glimpses of part of the total scene. Other obstacles are likely to arise when long-term survival is achieved. These obstacles include retroviral infections, transfer of prions and severe side effects of the massive immunosuppression which will be needed. Moral, ethical and religious concerns are under debate and the species-specific production of proteins of the foreign donor species developed for clinical use suddenly appears to be a greater problem than anticipated.
Animals↗