<p>Solid organ transplantation is today an established form of treatment for end-stage organ disease. Monitoring of graft function and pharmacological therapy constitutes a maze of clinical observations and histological evaluations of biopsy specimens; with the biopsy results playing a decisive role. The aims of this doctoral research were to investigate the feasibility of detecting acute rejection of transplanted organs and monitoring the effect of anti-rejection treatment, with the use of ultrasmall superparamagnetic iron oxide particles (USPIO) and magnetic resonance (MR) imaging with a clinical MR scanner.</p><p>Allogeneic and syngeneic heterotopic heart transplantations were performed in rats. Three different-sized USPIO were given to one allogeneic and one syngeneic group. The change in MR signal intensity (SI) over time was measured. An increase in SI was interpreted as damage to micro vessels due to the pronounced inflammatory reaction caused by acute rejection, which led to leakage of USPIO into the tissue. A decrease in SI was interpreted as normal vascular structure, since USPIO normally remains in the intravascular space. The same method, using one of the previously tested USPIO, was used in a treatment study in which acute rejection in transplanted rats was induced and subsequently treated. An attempt was also made to detect presence of macrophages in an acutely rejecting graft, since this cell type plays an important role in the acute rejection process; this was done by testing the ability of macrophages to phagocytose the UPSIO compound.</p><p>In permeability studies with MR imaging all three USPIO tested discriminated between rejecting and non-rejecting grafts without any overlap of the groups. Factors that contributed to the ability to distinguish between grafts were the size and half-life of the particle. We were also able to monitor effects of anti-rejection treatment by studying the vascular permeability of USPIO and MR imaging. We did not succeed in detecting macrophages in the rejecting grafts with USPIO and MR imaging.</p><p>This thesis presents a novel approach to detection of acute rejection of transplanted organs and to monitoring the effects of anti-rejection treatment using different USPIO contrast agents and MR imaging in a clinical MR scanner.</p>

Solid organ transplantation is today an established form of treatment for end-stage organ disease. Monitoring of graft function and pharmacological therapy constitutes a maze of clinical observations and histological evaluations of biopsy specimens; with the biopsy results playing a decisive role. The aims of this doctoral research were to investigate the feasibility of detecting acute rejection of transplanted organs and monitoring the effect of anti-rejection treatment, with the use of ultrasmall superparamagnetic iron oxide particles (USPIO) and magnetic resonance (MR) imaging with a clinical MR scanner. Allogeneic and syngeneic heterotopic heart transplantations were performed in rats. Three different-sized USPIO were given to one allogeneic and one syngeneic group. The change in MR signal intensity (SI) over time was measured. An increase in SI was interpreted as damage to micro vessels due to the pronounced inflammatory reaction caused by acute rejection, which led to leakage of USPIO into the tissue. A decrease in SI was interpreted as normal vascular structure, since USPIO normally remains in the intravascular space. The same method, using one of the previously tested USPIO, was used in a treatment study in which acute rejection in transplanted rats was induced and subsequently treated. An attempt was also made to detect presence of macrophages in an acutely rejecting graft, since this cell type plays an important role in the acute rejection process; this was done by testing the ability of macrophages to phagocytose the UPSIO compound. In permeability studies with MR imaging all three USPIO tested discriminated between rejecting and non-rejecting grafts without any overlap of the groups. Factors that contributed to the ability to distinguish between grafts were the size and half-life of the particle. We were also able to monitor effects of anti-rejection treatment by studying the vascular permeability of USPIO and MR imaging. We did not succeed in detecting macrophages in the rejecting grafts with USPIO and MR imaging. This thesis presents a novel approach to detection of acute rejection of transplanted organs and to monitoring the effects of anti-rejection treatment using different USPIO contrast agents and MR imaging in a clinical MR scanner.

Väntan på transplantation kan vara en komplex situation för patient och anhörig. Studiens syfte var att belysa vad patienter och deras anhöriga upplever när de står i kö för en organtransplantation. Metoden som användes var en kvalitativ ansats där fyra självbiografier lästes och analyserades. I resultatet framkom att upplevelserna startade med beskedet om att transplantation var nödvändig för den fortsatta överlevnaden, tills beskedet om transplantation kom och patienterna lades in för operation. Analysen av den insamlade datan resulterade i fem kategorier: Insikten om sjukdomens allvar, Mellan hopp och förtvivlan, Tankar kring döden, Samvetskval och Ett efterlängtat besked. Resultatet kan användas till att öka förståelsen hos vårdpersonal för vad patienterna och deras anhöriga genomgår känslomässigt under deras väntan på organtransplantation. / The waiting period for organ transplantation can be a complex situation for patients and their relatives. The purpose of the study was to enlighten the experiences of patients and their relatives when they stand in queue for organ transplantation. With a qualitative attempt four autobiographies were read and analyzed. The result showed that the experiences started with the information that transplantation was essential for the patients’ continuance of life, to when they were hospitalized for the operation. The analysis of the data resulted in five categories: The insight about the gravity of the disease, Between hope and despair, Thoughts surrounding death, Qualms of conscience and A call much longed for. The result can be used to increase the understanding for what patients and their relatives go through emotionally during their wait for organ transplantation among the nursing staff.

Source: Masters Abstracts International, Volume: 47-06, page: 3444. Advisers: Janet S. Butel; Linda B. Piller. Includes bibliographical references.

Background. Diabetes seems to be associated with an increased risk of fractures in the general population. We aimed to determine whether pre-transplant diabetes increases the risk of fractures among patients receiving solid organ transplantation. / Methods. We conducted a nested case-control study in a cohort of subjects 18 years and older who received a first solid organ transplantation in Quebec between January 1st 1986 and July 31st 2005, and who were covered by the RAMQ drug plan at least 1 year before the transplantation and 3 months after the date of discharge from the transplantation hospitalization. Cases were subjects from the cohort who had sustained a fracture between the date of discharge from the hospitalization for transplantation and the end of the study period or the patient's death. The fracture date was the case index date. All incidental fractures were included except fractures of the skull, phalanges of the hand and foot, multiple fractures and pathological fractures, and were identified by medical service claims. Controls were matched to cases on the type of organ transplanted and on the date of the transplantation (+/- 3 months). Crude and adjusted odds ratios (OR) were obtained with univariate and multivariate conditional logistic regression models. / Results. The study included 238 cases and 873 controls. Pre-transplant diabetes was present in 30% of the cases and 22% of the controls (crude OR: 2.16, 95% CI: 1.7--2.8). After adjusting for potential confounders, pre-transplantation diabetes remained a significant risk factor for fractures (adjusted OR: 1.94, 95% CI: 1.5--2.6). / Conclusion. Pre-transplant diabetes appeared to significantly increase post-transplant fractures among adults receiving solid organ transplantation.

Die Wiederaufnahme einer produktiven Beschäftigung ist ein wesentliches Ziel der Rehabilitation nach Organtransplantation. In Deutschland ist jedoch die Mehrheit der organtransplantierten Patienten im erwerbsfähigen Alter frühberentet. Die vorliegende Arbeit hat zum Ziel, die Beschäftigungssituation Organtransplantierter und mögliche Einflussfaktoren am Universitätsklinikum Leipzig zu untersuchen. Dabei interessiert insbesondere der Einfluss der psychischen Komorbidität auf die berufliche Reintegration. Im Rahmen einer katamnestischen Querschnittsstudie wurden insgesamt 82 Patienten ein bis acht Jahre nach Leber-, Nieren- oder Pankreastransplantation befragt. Neben der Beschäftigungssituation und der psychischen Komorbidität (SKID-I, HADS), wurden soziodemografische, medizinische und arbeitsbezogene Merkmale sowie die gesundheitsbezogene Lebensqualität (EORTC QLQ-C30) als potenzielle Einflussfaktoren auf die Arbeitswiederaufnahme und die psychische Komorbidität erhoben. Die Auswertung der Daten zeigt, dass berufstätige Organtransplantierte eine signifikant bessere gesundheitsbezogene Lebensqualität haben und signifikant seltener unter psychischer Komorbidität leiden als frühberentete Organtransplantierte. Dieser Zusammenhang sollte Beachtung finden bei der Rehabilitation und Nachsorge transplantierter Patienten. Ziel muss es sein, die berufliche Reintegration zu fördern und gleichzeitig psychische Komorbidität auch im Langzeitverlauf nach Transplantation frühzeitig zu erkennen und adäquat zu behandeln, um das Risiko für Frühberentung zu senken und eine verbesserte Lebensqualität und damit auch den Gesamterfolg der Transplantation langfristig zu sichern.

Brain death has adverse effects on the organ donor, increasing organ dysfunction and affecting transplantation outcomes. It can also render organs unsuitable for transplantation. Another determinant of organ quality is ischaemia-reperfusion injury, which limits ischaemic storage time for hearts to six hours. The aim of this thesis was to investigate the effectiveness of hormone resuscitation (HR) of the donor to ameliorate the effects of brain death. Another aim was to develop a donor management and organ preservation strategy to ameliorate the effects of ischaemia-reperfusion injury on the heart, thereby extending ischaemic preservation times. A porcine model of the brain-dead multi-organ donor with orthotopic cardiac transplantation was utilised. Donor HR was shown to improve cardiac contractility and haemodynamics, thereby reducing inotrope requirements. A follow-up study investigating the effects of three different donor management protocols demonstrated that donor haemodynamics, renal arterial flow and creatinine clearance were superior in HR animals compared with animals treated with noradrenaline or intravenous fluid alone. Noradrenaline was associated with a significant deterioration in pulmonary function (PaO2 and alveolar-arterial oxygen gradient) and a decline in donor pH. HR was not associated with any detrimental effects on the lungs, liver or pancreas compared with the other two groups. Preservation strategies incorporating glyceryl trinitrate (GTN) and cariporide, a Na+-H+ exchange inhibitor, were investigated to safely extend cardiac ischaemic preservation times. Pre-treatment with intravenous cariporide prior to heart explantation (donor) and reperfusion of the transplanted heart (recipient) was shown to effectively extend ischaemic time to 14 hours, evidenced by weaning off cardiopulmonary bypass. GTN and cariporide-supplemented Celsior, used as a cardioplegic/storage solution, was also effective in extending preservation time to 14 hours, with superior cardiac contractility compared with cariporide pre-treated hearts. Both treatments also ameliorated reperfusion injury, stabilising haemodynamics for up to three hours post-bypass. This thesis has demonstrated the effectiveness of HR to ameliorate the negative effects of donor brain death. It also provides evidence that combined GTN and cariporide-supplemented Celsior improves long-term preservation of the donor heart. These strategies offer the potential to increase the proportion of transplantable organs, to improve donor organ quality, and thereby improve transplantation outcomes.

<p>Väntan på transplantation kan vara en komplex situation för patient och anhörig. Studiens syfte var att belysa vad patienter och deras anhöriga upplever när de står i kö för en organtransplantation. Metoden som användes var en kvalitativ ansats där fyra självbiografier lästes och analyserades.</p><p>I resultatet framkom att upplevelserna startade med beskedet om att transplantation var nödvändig för den fortsatta överlevnaden, tills beskedet om transplantation kom och patienterna lades in för operation.</p><p>Analysen av den insamlade datan resulterade i fem kategorier: Insikten om sjukdomens allvar, Mellan hopp och förtvivlan, Tankar kring döden, Samvetskval och Ett efterlängtat besked. Resultatet kan användas till att öka förståelsen hos vårdpersonal för vad patienterna och deras anhöriga genomgår känslomässigt under deras väntan på organtransplantation.</p> / <p>The waiting period for organ transplantation can be a complex situation for patients and their relatives. The purpose of the study was to enlighten the experiences of patients and their relatives when they stand in queue for organ transplantation. With a qualitative attempt four autobiographies were read and analyzed.</p><p>The result showed that the experiences started with the information that transplantation was essential for the patients’ continuance of life, to when they were hospitalized for the operation.</p><p>The analysis of the data resulted in five categories: The insight about the gravity of the disease, Between hope and despair, Thoughts surrounding death, Qualms of conscience and A call much longed for. The result can be used to increase the understanding for what patients and their relatives go through emotionally during their wait for organ transplantation among the nursing staff.</p>

Chronic immune insult and immunosuppressant-related toxicities have remained an enduring challenge in organ transplantation. Long-term survival of transplant patients has improved marginally in recent decades due to these challenges. To circumvent these issues, transplant investigators have researched immune tolerance mechanisms that demonstrate potential to induce immunosuppression and rejection-free survival in the clinic. One mechanism in particular, the liver tolerance effect, has already demonstrated this experimentally and clinically. Liver transplants in experimental models and human patients have exhibited the ability to become spontaneously accepted without being rejected by the recipient’s immune system. Research in recent decades has revealed that the liver parenchymal and non-parenchymal cell populations harbor potent immunomodulatory properties. In the context of liver transplantation, it has been found that two cell populations in particular, the mesenchyme-derived liver sinusoidal endothelial cells and hepatic stellate cells, mediate the induction of liver transplant tolerance through a mechanism known as mesenchyme-mediated immune control.

Feo-hifomicose refere-se a infecções por fungos pigmentados escuros. Revisamos a casuística brasileira entre 1953 e 2010, apresentando as características clínico-epidemiológicas e diagnósticas de 17 casos. Nas quais a coloração de hematoxilina-eosina foi usada para visualizar alterações estruturais nas lesões; a coloração da prata para identificação dos microrganismos; e coloração de Fontana-Masson confirmou a melanina na parede fúngica. Os fungos cresceram sob aspecto de micélio e produziam pigmentos de melanina, que dão às colônias cor negra característica. A observação das características microscópicas dos cultivos forneceu a identificação etiológica. A feo-hifomicose está amplamente disseminada no Brasil. Entretanto, é subestimada devido a fixação das biopsias em formol, o que impede o isolamento em cultivos. / Phaeohyphomycosis refers to infection caused by darkly pigmented fungi. We reviewed the Brazilian casuistic from 1953 to 2010 and presented the clinicalepidemiologic and diagnostic features of addictional 17 cases. In the cases hematoxilin and eosin stain was used to look for structural changes of the infected lesion; Gomori’s methenamine-silver stain identified these organisms; and Fontana-Masson staining confirm the presence of melanin fungal cell wall. The organisms formed mycelial colonies and produced melanin-like pigments that give the colonies the characteristic dark color. The microscopic study of cultures identified etiology. The phaeohyphomycosis is a widespread tropical disease in Brazil. However, it is underestimated due to formalin fixation tissue specimens that oppose the prior cultures.