Transplantation indications

Cyciosporine Aiready known from RCTs Dose/duration of use, long-term effects Reasonable quality Confounding by renal transplant indication... 

Currently, since the safety and efficacy of SRL has not been established in liver or lung transplants, it is recommended that its use be avoided in these populations immediately following transplant. In contrast, limited data on the use of SRL in heart transplantation indicate benefit in reversing acute rejection in patients who do not respond to antilymphocyte therapy. Furthermore, SRL may slow the progression of vasculopathy, which may have an impact on chronic rejection and long-term patient survival after heart transplantation. ... 

Goulet O, et al. Intestinal transplantation Indications, results and strategy. Curr Opin Clin Nutr Metab Care 2000 3 329-338. 

We have observed decreases in serum bilirubin levels of up to 50% and appearance of conjugated bilirubin products in the native bile up to nine weeks post transplantation, indicating metabolic activity in the transplanted cells. While promising, these results were difficult to consistently reproduce, and successful hepatocyte transplantation was limited by cell injury and hypoxia at the time of transplantation. Cell death prevented consistently adequate cell mass engraftment to replace function. 

Alegre C, Jimenez G, Manrique A, Abradelo M, Calvo J, Loinaz C, et al. Everolimus monotherapy or combined therapy in liver transplantation indications and results. Transplant Proc June 2013 45(5) 1971-4. PubMed PMID 23769086. Epub 2013/06/19. eng. 

Cooper DKC, Taniguchi S (1996) Heterotopic heart transplantation - indications, surgical techniques and special considerations. In Cooper DKC, Miller LW, Patterson GA (eds) The transplantation and replacement of thoracic organs. Kluwer, Dordrecht, pp 353-365... 

Fig. 4.1.8. Representative axial computed tomography images demonstrating extensive retrogastric and paraaortic lymphadenopathy following liver transplantation indicating post-transplantation lymphoproliferative disease...

Starnes VA, Barr ML, Cohen RG. Lobar transplantation indications, technique, and outcome. J Thorac Cardiovasc Slug 1994 108 403-411. 

Immunosuppressive agents (immunosuppressants) are drugs that attenuate immune reactions. An application is indicated in case our immune system reacts inadequately leading to serious diseases or normal immune reactions are unwanted, e.g., following transplantations. 

Indications for the clinical use of immunosuppressive drugs are transplantation, autoimmune diseases, chronic inflammatory diseases, allergic reactions. 

Treatment with specific antibodies (ALG, ATG, anti-CD3, anti-CD25) is indicated during the induction phase after transplantation and in the case of acute rejection for short time periods. Therapy with nonhuman antibodies may cause sensitization. Muromonab-CD3 might initiate a cytokine release syndrome (fever, chills, headache). 

Rapamycin has been known for many years to possess immunosuppressive activity by interfering with the activation of B- and T-cells by interleukin-2. Indeed the first clinically approved indication for rapamycin was renal transplantation. Currently, rapamycin and RAD001 also show promise in liver transplantation and cardiac transplantation, respectively. Generally, treatment protocols utilize a combination of an mTORCl inhibitor, a calcineurin inhibitor and steroids to optimize immunosuppression and minimize nephrotoxicity and other side effects. Rapalogs are also... 

The genetic defects known as thalassemias result from the partial or total absence of one or more a or P chains of hemoglobin. Over 750 different mutations have been identified, but only three are common. Either the a chain (alpha thalassemias) or P chain (beta thalassemias) can be affected. A superscript indicates whether a subunit is completely absent (a or p ) or whether its synthesis is reduced (a or P ). Apart from marrow transplantation, treatment is symptomatic. 

Parks, D.A., Tan, S., Poplawski, S.C., Baldwin, S. and Sweeney, S.D. (1992). Uric acid oxidation products indicator of oxidant stress in human liver transplantation. Gastroenterology 102, A232. 

Hepatic reperfusion injury is not a phenomenon connected solely to liver transplantation but also to situations of prolonged hypoperfusion of the host s own liver. Examples of this occurrence are hypovolemic shock and acute cardiovascular injur) (heart attack). As a result of such cessation and then reintroduction of blood flow, the liver is damaged such that centrilobular necrosis occurs and elevated levels of liver enzymes in the serum can be detected. Particularly because of the involvement of other organs, the interpretation of the role of free radicals in ischaemic hepatitis from this clinical data is very difficult. The involvement of free radicals in the overall phenomenon of hypovolemic shock has been discussed recently by Redl et al. (1993). More specifically. Poll (1993) has reported preliminary data on markers of free-radical production during ischaemic hepatitis. These markers mostly concerned indices of lipid peroxidation in the serum and also in the erythrocytes of affected subjects, and a correlation was seen with the extent of liver injury. The mechanisms of free-radical damage in this model will be difficult to determine in the clinical setting, but the similarity to the situation with transplanted liver surest that the above discussion of the role of XO activation, Kupffer cell activation and induction of an acute inflammatory response would be also relevant here. It will be important to establish whether oxidative stress is important in the pathogenesis of ischaemic hepatitis and in the problems of liver transplantation discussed above, since it would surest that antioxidant therapy could be of real benefit. 

The ventricular assist device (VAD) is a surgically implanted pump that reduces or replaces the work of the right, left, or both ventricles. Ventricular assist devices are currently indicated for short-term support in patients refractory to pharmacologic therapies, as long-term bridge therapy (a temporary transition treatment) in patients awaiting cardiac transplant, or in some instances, as the destination therapy (treatment for patients in lieu of cardiac transplant for those who are not appropriate candidates for transplantation).1 The most common complications are infection and thromboembolism. Other... 

Cardiac transplantation is one option for patients with severe heart failure. Candidates for cardiac transplantation generally present with New York Heart Association (NYHA) class III or IV symptoms and have an ejection fraction of less than 25%.1,3 The general indications for cardiac transplantation include rapidly declining cardiac function and a projected 1-year mortality rate of greater than 75%. Mechanical support with an implantable left ventricular assist device may be appropriate while patients await the availability of a viable organ.1,3 Some additional reasons for heart transplant include ... 

Colonization at multiple distinct body sites or with high density of Candida species, however, often precedes invasive infection. Preemptive antifungal therapy may be indicated in colonized high-risk populations such as neutropenic fever, transplant recipients, or following major abdominal surgery. 

Hu H, Aizenstein BD, Puchalski A, Burmania JA, Hamawy MM, Knechtle SJ. Elevation of CXCR3-binding chemokines in urine indicates acute renal-allograft dysfunction. Am J Transplant 2004 4 432M37. 

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