Fungal infection in cardiothoracic transplant recipients: outcome without systemic amphotericin therapy.

Transplant recipients require immunosuppression to prevent allograft rejection, placing them at risk of opportunistic infections including fungal infection. Difficulties in managing fungal infections include: establishing diagnosis, poor treatment response, drug interactions and toxicity. We report our single centre experience of treating fungal infections using systemic non-Amphotericin current generation antifungals. Patients receiving inpatient antifungal therapy from September 2005 to December 2010 were identified from pharmacy records. Fungal infections were retrospectively classified according to European Organization for Research and Treatment of Cancer (EORTC) criteria. Treatment outcomes were classified in a manner similar to those used in clinical trials. Two hundred and forty-nine recipients received antifungal treatment, 204 lungs and 45 hearts. One hundred and one patients received Voriconazole, 82 Caspofungin and 65 received both agents. One patient was unsuccessfully treated with additional Amphotericin. Treatment duration varied from 1.5 to 12 weeks. One hundred and sixty-five patients had a complete response, 24 had a partial response and in 60 patients treatment was unsuccessful. The response to systemic non-Amphotericin based antifungal therapy was high. We propose that diagnostic criteria without positive identification of a fungus allow treatment to be started early with few clinically relevant side effects.

Native valve Aspergillus endocarditis complicating lung transplantation.

We present 2 cases of Aspergillus endocarditis occurring in lung transplant recipients, both of whom were treated with early surgical intervention and triazole anti-fungal agents. Neither had evidence of airway colonization/infection with Aspergillus post-transplant, suggesting hematogenous spread of fungi at the time of surgery as a possible mechanism of infection. One case was successfully treated and discharged from the hospital, but, despite initial recovery, death occurred 10 months later due to a recurrence of Aspergillus endocarditis. Aspergillus endocarditis should be considered a relapsing disease and survivors of the condition should receive ongoing anti-fungal therapy.

Alteration in CD45RBhi/CD45RBlo T-cell ratio following CD45RB monoclonal-antibody therapy occurs by selective deletion of CD45RBhi effector cells.

Tolerance induction by CD45RB monoclonal antibody (mAb) in murine allograft models is associated with an alteration in the CD45RBlo/CD45RBhi T-cell ratio in favor of CD45RBlo T cells, which can function as regulatory cells and promote tolerance. It has been proposed that inversion of the CD45RBhi/CD45RBlo normal T-cell ratio by mAb can occur by down-regulation of CD45RB surface molecules expressed by T cells. Because CD45RB mAb infusion can lead to a reduction in peripheral T cells, we tested whether other mechanisms might participate in the inversion of the CD45RBhi/CD45RBlo ratio, including apoptosis of CD45RBhi cells. We report that CD45RB mAb led to rapid elimination of both CD4+ and CD8+ T cells in vitro. Importantly, CD45RB mAb selectively eliminated CD45RBhi T cells without affecting the viability of CD45RBlo T cells. Furthermore, the death of T cells occurred with a reduction in mitochondrial transmembrane potential and DNA fragmentation but with little evidence of nuclear condensation and cell shrinkage typically found with cells undergoing apoptosis. We propose that CD45RB mAb therapy may promote a dominant regulatory T-cell population that has the capacity to inhibit rejection by the selective elimination of CD45RBhi effector T cells. This occurs by a process that does not involve the classic morphologic features of apoptosis. Strategies that facilitate an inversion of the CD45RBhi/CD45RBlo T-cell subset ratio may improve the efficacy of CD45RB mAb, and therapeutic measures that prevent deletion of CD45RBhi T cells may need to be avoided to achieve tolerance clinically.

Significance of endothelial cell survival programs for renal transplantation.

Initial and longer term kidney transplant function is determined in part by the renal allograft microcirculation because it provides a thromboresistant surface, regulates cellular infiltration, and elaborates paracrine and autocrine growth and survival factors. Loss of endothelial-derived signaling mediators accelerates vascular injury and endothelial cell (EC) death. EC apoptosis is implicated in accelerated allograft vasculopathy and premature loss of organ function. Renal allograft EC injury and replacement by recipient-derived repair mechanisms has long been proposed to influence allograft acceptance and function. Repair of cellular injury in allografts is linked with cell-survival mechanisms, but few precise indicators exist to predict recovery and repair in organ transplants. The significance of the growth phenotype of the microvascular endothelium for acute and longer term renal allograft survival is presented.

Infection imaging with radiopharmaceuticals in the 21st century

Infection continues to be a major cause of morbidity and mortality worldwide. Nuclear medicine has an important role in aiding the diagnosis of particularly deep-seated infections such as abscesses, osteomyelitis, septic arthritis, endocarditis, and infections of prosthetic devices. Established techniques such as radiolabelled leucocytes are sensitive and specific for inflammation but do not distinguish between infective and non-infective inflammation. The challenge for Nuclear medicine in infection imaging in the 21st century is to build on the recent trend towards the development of more infection specific radiopharmaceuticals, such as radiolabelled anti-infectives (e.g. 99mTc- ciprofloxacin). In addition to aiding early diagnosis of infection, through serial imaging these agents might prove very useful in monitoring the response to and determining the optimum duration of anti-infective therapy. This article reviews the current approach to infection imaging with radiopharmaceuticals and the future direction it might take