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Heart transplantation (HTx) is a method of treatment for patients with end-stage heart failure with severe symptoms despite complex therapy. Post-transplant difficulties include acute rejection and infectious complications, which are the most common reason of morbidity and mortality in the first year after heart transplant. It requires the patient to remain on immunosuppressive medication to avoid the possibility of graft rejection. Therefore the range of infection is much larger. The diagnosis and treatment of viral, bacterial and fungal infections is often difficult.Key words: heart transplantation - immunosuppression - infection.

The aim is to give basic information about inflammatory bowel disease (IBD) during pregnancy, to highlight the importance of treatment in pregnancy and also show our own experience with the issue.Original work - a retrospective study.Department of Obstetrics and Gynecology, Hospital Hořovice.We provide basic overview information about inheritance, fertility, mutual influence of IBD and pregnancy therapy in pregnancy and childbirth options for patients with IBD. We present also the results of the group of 17 patients with varying degrees of disability IBD (including patients after previous surgeries - bowel resection, hemicolectomy, ileostomy or with a pouch) that gave birth to our workplace.A crucial factor for good results is the degree of inflammation at the time of conception and during pregnancy. If the disease is inactive and nutrition of the diseased sufficient, there is no decrease in fertility, course of pregnancy is seamless, there is no greater risk of deterioration of disease in pregnancy and pregnancy do not differ from the normal population. The opposite situation occurs if there is a pregnancy at the time of disease activity. Then up to 75% pregnancy courses with big problems, fertility is declining, inflammation is also worsening and the risk of exacerbations increases during pregnancy, which aggravates the course of pregnancy and childbirth and has a negative effect on the fetus. Pregnancy is therefore necessary to plan for a longer period of disease stabilization and continue chronic medication and not discontinue drugs for fear of negative impact of medications on fetal development. On the contrary, active inflammation of the mother during pregnancy poses a greater risk to the fetus than adequate treatment. Commonly used drugs-aminosalicylates, corticosteroids, immunosuppressants and biological therapy appears to be safe and well tolerated during pregnancy. Method of delivery is individual and depends on the form and location of the inflammation and the preceding operations.

Kidney transplantation represents the best treatment of end stage renal diseases in respect of patient survival and quality of life. Despite many advances in immunosuppression and surgical techniques, many kidney grafts are being lost in the long term, mainly due to chronic rejection and recurrence of glomerulonephritis. Calcineurin drug nephrotoxicity, which was overestimated in last decades, seems to have only minor impact on graft survival if any. Despite better understanding of mechanisms of kidney graft injuries, which are reflected by never-ending changes in histological classification systems, optimal treatment strategies are not available for majority of cases. Prospective randomized trials generated from transplant community are therefore warranted to solve many questions about the therapy.Key words: chronic rejection - kidney transplantation - nephrotoxicity - recurrence.

Sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease) is a very rare disease belonging to a group of histiocytoses (more precisely non-Langerhans cell histiocytoses). Rosai-Dorfman disease is characterised by the presence of atypical histiocytic cells in the sinuses of lymph nodes or in the extranodal lymphoid tissue, absorbing lymphocytes and plasma cells. The structure and function of the absorbed cells is not impaired and they can leave histiocytes as viable cells. This effect is called emperipolesis, whereas ingestion of cells with their destruction is called phagocytosis. In our text we describe a patient with this disease located, characteristically, in supraclavicular lymph nodes, but also in mediastinal lymph nodes. Along with lymphadenopathy skin alterations appeared which were both clinically and histologically described as eczema dermatitis. At the same time as lymphadenopathy also strong headaches started which the patient had never suffered before. Within the first-line treatment prednisone was administered, but no effect was achieved. 2-chlorodeoxyadenosine in 5 mg/m2 s. c. dose was used in the second-line treatment, for 5 successive days in monthly intervals. There were four cycles of this treatment administered overall. Therapy was tolerated without any manifestations of toxicity. Already after the 1st cycle skin alterations as well as headaches entirely disappeared. To assess the effect of treatment the PET/CT examination with 18F-fluorodeoxyglucose (FDG-PET/CT) was made. After 4 cycles of treatment the mediastinal lymph nodes diminished to a physiological size and the accumulation of fluorodeoxyglucose in them was assessed as physiological. Lymphadenopathy in the neck area also significantly diminished by 50-75 % and the accumulation of fluorodeoxyglucose was reduced as well, though it did not reach the norm. Therefore we evaluate the effect of treatment as a partial remission with complete disappearance of skin alterations and headaches. The cause of the eczema and headaches has not been clarified, however considering the same time of their arising and then disappearance after the application of 2-chlorodeoxyadenosine the causal connection with Rosai-Dorfman disease is likely.Castlemans disease - lenalidomide - Rosai-Dorfman disease - rituximab - sinus lymphadenopathy with massive lymphadenopathy - thalidomide - 2-chlorodeoxyadenosine.

Dermatomyositis is an idiopathic inflammatory disease affecting proximal skeletal muscles and the skin. The manifestation can be acute (over weeks) or chronic (over months to years). Dermatomyositis affects children as well as adults. Very helpful for the diagnosis are laboratory, clinical, EMG and histopathological tests. The disease responds positively to corticosteroid, immunosuppressive or immunoglobulin therapy. Three various cases of DM are described in this article.dermatomyositis , symptoms, diagnostic criteria, treatment.

Autoimmune uveitis is a sight threatening disease which in many cases fails to respond to conventional immunosuppressive or biological therapy. The research in experimental models of autoimmune uveitis helps to find new therapeutical strategies. The aim of this study is to present the clinical and histological signs of experimental autoimmune uveitis (EAU) in mice.EAU was induced in C57BL/6 mice by subcutaneous application of IRBP (interphotoreceptor retinoid binding protein) in complete Freunds adjuvant and intraperitoneal application of pertussis toxin. Clinical evaluation of uveitis was performed in vivo using special imaging system with otoscope. Histological evaluation of uveitis was performed at day 35 post induction of EAU on hematoxylin and eosin stained frozen sections. Clinical and histological grading was used to assess the inflammation intensity of EAU.The intensity of inflammation is depicted on representative fundus images and histological images of retina at day 35 post induction.The model of EAU is robust and reproducible and allows us to study the immunopathological mechanisms of inflammation and its regulation. The inflammatory signs in our model are similar to findings of posterior uveitis of autoimmune etiology in humans, thus we may apply our experimental results in human medicine.

Infective endocarditis in a patient after kidney transplantation is a serious infective complication which increases the risk of loss of the graft and also the mortality of patients. The most important predisposing factor is the immunosuppressive therapy - mainly induction immunosuppression.Material and case description: 250 patients underwent kidney transplantation throughout the period of 12 years in the Transplant Center Martin. This set of patients included 5 patients (2 %) after heart valve replacement. We present the case of a patient after kidney transplantation with development of endocarditis of the bioprosthesis of the aortic valve one month after successful kidney transplantation. Diagnostics of endocarditis by standard procedures (examination by transthoracic echocardiogram, transesophageal echocardiography, hemocultures) was unsuccessful. We rarely diagnosed endocarditis only by PET-CT examination with a consequent change of the antibiotic treatment and successful managing of this post-transplant complication.Endocarditis after kidney transplantation is a serious complication which significantly worsens the mortality of patients. The risk of development of infective endocarditis after transplantation is also increased by induction, mainly by antithymocyte globulin. Diagnostics only by PET-CT examination is rare; however, in this case it fundamentally changed the approach to the patient and led to a successful treatment.

Patients with chronic lymphocytic leukemia have disrupted cellular and humoral immunity with quantitative and qualitative impairment of the cells of the immune system. Immunity disbalance leads to increased incidence of infections and autoimmune cytopenias. Supportive care for chronic lymphocytic leukemia focuses on prevention and treatment of these complications and consists of antimicrobial prophylaxis, substitution of immunoglobulins, immunosuppressive therapy, growth factors and blood transfusions.

Glucocorticoids are derivatives of natural human glucocorticoid cortisol. There are used for treatment of a number of diseases and disorders for more than 65 years mainly because of their immunosuppressive properties. However, their use is accompanied by various side effects that have to be considered when treating patients. The article summarizes biological effects of glucocorticoids, main indications for their use, their side effects and precautions necessary to bear in mind during treatment.

Therapy of Waldenström´s macroglobulinaemia (WM) is indicated in patients with clinically relevant symptoms. Therapeutic plasmapheresis should be performed in cases with hyperviscosity. The intensity of chemotherapy should be adjusted to the degree of cytopenia. Monotherapy with rituximab is recommended in cases with severe cytopenia, also combination of rituximab with dexamethasone should be possible. Patients with symptomatic WM without severe cytopenia should received a rituximab-containing regimens, optimal variant is combination of rituximab + dexamethasone + alkylation drug (such as cyclophosphamide or bendamustine). Possible treatment combinations are for instance R-CHOP (rituximab, cyclophosphamide, vincristine, and prednisone), R-COP (rituximab, cyclophosphamide, and prednisone), or RCD (rituximab, cyclophosphamide, and dexamethasone). The choice of regimen in individual patients will take into consideration performance status, clinical features including renal function, comorbidities and potential candidacy for stem cell transplantation.Chlorambucil and rituximab is possible treatment options for older patients. The choice of treatment of WM relapse depends on the time of treatment response. Retreatment with primary therapy may be appropriate in patients with duration of treatment response at least 2 years. Other treatment possibilities for WM relapse are regimens containing fludarabine, cladribine or bortezomib. Autologous transplantation of peripheral blood stem cells is feasible therapeutic option for relapsed WM in younger, fitter patients with aggressive chemosensitive disease.

Authors compared clinical and economic effeciency of treatment of the classical corticosteroids therapy and modern immunosuppressive treatment or their combination. Retrospective evaluation carried out in 2012, covering 2006-2011, monitored sample of 27 patients, 16 women and 11 men, 45 eyes with disabilities. The average age in the last year of follow-up monitoring was 30.2, ranging from 14 to 76 years. The mean duration of disease for the whole sample is 16.5 years with a range from 6 to 36 years. Three basic diagnoses were included in investigated group: chronic iridocyclitis in 59 % of eyes, intermediate uveitis in 30 % of eyes and sympathetic ophthalmia in 11 % of eyes. The optimal treatment not be determined, however, combined corticosteroid sparing therapy was the most beneficial to maintain in terms of visual acuity with minimal side effects and cost effectiveness. Successful outcomes of treatment were observed for intermediate uveitis, because the visual acuity improved in nine letetters of ETDRS chart in the study. Satisfactory treatment was proved in chronic iridocyclitis and sympathetic ophthalmia in general, because visual acuity improved in a few letters of ETDRS chart, in the same line as in the beginning of the six-year follow-up. Rounded average annual prize for treatment including pharmacotherapy, outpatient and inpatient care and laboratory follow-up was in chronic iridocyclitis € 990, in intermediate uveitis € 310 and sympathetic ophthalmia € 1550. Pharmacotherapy exceeded the financial appraisal of specialized medical and inpatient care in total cost. Key words: uveitis, corticosteorids, immunosuppression, costeffectivness.

The development of immunosuppression has significantly affected the development of liver transplantation and has helped to switch from the experimental method to a standard treatment of life threatening liver conditions. Tacrolimus is the basic immunosuppressant for patients after a liver transplant and thanks to its prolonged-release dosage form, which due to its simplicity and reliability of use, replaces tacrolimus twice daily early after the transplant and in the longterm administration, will apparently, for a while, defend its position. Other widely used medicines include mycophenolic acid and mTOR inhibitors, sirolimus and everolimus. The induction with antilymphocyte antibodies is used in less than 10% of liver recipients. Only a few new immunosuppresants in this century have passed later stages of clinical studies; the last 2 medicines registered for patients after liver transplantation include Advagraf (Astellas) and Certican (Novartis). Personalised immunosuppression should respect at least the following basic clinical situations: recipients renal function, hepatitis C virus infection, and hepatocellular carcinoma as the liver transplant indication. The results of immunotolerance bio-marker research are necessary for a more successful conduct of protocols minimising immunosuppression and leading to immunotolerance, especially under the efforts of complete withdrawal of immunosupression.

The history of liver transplants extends over more than 60 years. During the first 10 years the operations were carried out only as experiments and primarily focused on designing complex surgical techniques. In the 1960s the research focused on the development of immunosuppressants and the first clinical operations were performed. However, the outcomes of these interventions were very poor. The subsequent 2 decades witnessed the development of new and very efficient immunosuppressants, significantly improving patient survival rates. The number of operations and sites performing these interventions increased. In the United States in 1983, liver transplants were recognised as a clinical treatment method for liver conditions where all conservative options had failed. In the same year the first successful liver transplant was performed in Czechoslovakia. New surgical techniques bringing significant reduction of blood loss during the operation, reduction of over extensive grafts, splitting operations - when one organ may be used for 2 recipients - and collection of liver lobes from living donors resulted in a further increase in the number of transplants. The development of new immunosuppressive protocols have contributed to further improved survival rates of the patients while the majority of transplant sites achieve the longterm survival of 90%. However, the future of transplants lies in inducing the immunological tolerance of the body towards the transplanted organ with no immunosuppressive treatment administered.

Myelodysplastic syndrome is one of the most common hematology diseases in the age over the 60. Until recently the therapy of this disease was frustrating and often based only on supportive care. The last decade witnessed the emergence of promising drugs that represent a major breakthrough in the therapy and interest of decoding of the pathogenesis of this disease. In our work we summarize the evolution of MDS therapy with accent on the new drugs contribution.

Thalidomide, the first clinically available immunomodulatory drug, reaches monotherapy treatment response in about 1/ 3 of significantly pretreated patients with multiple myeloma, and in combination with glucocorticoids approximately 50% response rate. After addition of conventional cytostatic into the triple combination, therapeutic response is achieved in 80% of untreated patients or about 60% of pretreated patients. Therapeutic response is achieved even in 1/3 of patients with refractory multiple myeloma resistant to other available treatment. With regard to the frequency of adverse effects, particularly peripheral polyneuropathy, its use as maintenance therapy was nearly abandoned. The combination of thalidomide and bortezomib has a high therapeutic potential that was accompanied by a high frequency of peripheral polyneuropathy in entry studies. After optimizing bortezomib schedule and route of administration, which lead to significant reduction in the frequency of polyneuropathy, this combination is currently a very interesting therapeutic alternative for clinical practice. This is one of the most economically available treatment regimens combining the benefits of two major drug classes in the treatment of multiple myeloma - proteasome inhibitor and imunumodulatory drugs. There is also a renewed interest in thalidomide following sharp decline in its use in recent years in the Czech Republic. Comprehensive work is focused on summarizing the longterm experience with thalidomide, with special reference to combination with bortezomib.

Microscopic colitis is characterized by chronic or intermittent watery diarrhoea. Microscopic colitis is a common cause of chronic diarrhoea in predominantly older adults. The underlying mechanism in the pathogenesis of microscopic colitis remains unspecified. Microscopic colitis including colitis collagenous, lymphocytic, microscopic colitis with incomplete findings, minimal change colitis, eosinophilic colitis, Brainerd´s diarrhoea, graft-versus-host disease, mastocytic enterocolitis and postinfectious irritable bowel syndrome. Careful consideration of the clinical features and colonic mucosal biopsies usually lead to correct diagnosis. Treatments of microscopic colitis were based primarily on case reports and personal experience. Many medications have been proposed that either offer symptomatic relief (loperamide, cholestyramine) or had anti-inflammatory or immunosuppressive properties (aminosalicylates, steroids, adalimumab, azathioprine).

We summarize recommendations for glomerulonephritis treatment, established by internationally recognized experts in the field and sponsored by KDIGO (Kidney Disease Improving Global Outcomes). Up till now, the KDIGO review has been the most prestigious analysis of therapeutic trials on immunosuppressive treatment of glomerulonephritides. The 167 recommendations addresses the following forms of glomerulopathies: steroid-sensitive nephrotic syndrome and steroid resistant nephrotic syndrome in children; minimal change disease and idiopathic focal segmental glomerulosclerosis in children and adults; idiopathic membranous nephropathy; idiopathic membranoproliferative glomerulonephritis; glomerulonephritis associated with infection; immunoglobulin A nephropathy and Henoch-Schönlein purpura nephritis; lupus nephritis; pauci-immune focal and segmental necrotizing glomerulonephritis; and anti--glomerular basement membrane antibody glomerulonephritis. We focused our attention on progress in this topic in the last decade.

Until 2011, the gold standard of treatment for patients with AL amyloidosis was the combination of alkylating cytostatics (melphalan or cyclophosphamide) and dexamethasone. For a selected group of patients under 65 years of age with only moderate damage to their body caused by amyloid and with good cardiac function (EF40%), high-dose chemotherapy with autologous hematopoietic cell transplantation seems to be optimal. Patients with AL amyloidosis and low bone marrow plasma cell count generally undergo the harvest of hematopoietic cells from peripheral blood, followed by high-dose chemotherapy immediately after they are diagnosed. In contrast to multiple myeloma, high-dose chemotherapy is not preceded by several months of conventional treatment. The year 2012 witnessed a release of reports about extensive experience with new drugs that were used in Phase I and Phase II clinical trials, and in isolated cases also in Phase III, for the treatment of patients with AL amyloidosis. Based on these studies it can be concluded that among the new available drugs (bortezomib, thalidomide and lenalidomide) bortezomib is the drug with the greatest curative effect in patients with AL amyloidosis; it achieved 24-37% of complete remissions in monotherapy. The greatest number of treatment responses was reported during the treatment that combined bortezomib, alkylating cytostatics and dexamethasone. This treatment showed significantly more treatment responses during the first-line drug therapy than during therapies that followed. Clinical trials with lenalidomide combined with other drugs saw a lower number of treatment responses than the number described in treatment with bortezomib combined with other drugs. That is the reason why lenalidomide combinations are not considered the optimal first-line therapy, with the exception of AL amyloidosis with bortezomib contraindication (severe neuropathy caused by AL amyloidosis). It was confirmed that lenalidomide combined with other drugs could cause remission in patients whose disease was resistant to the initial bortezomib therapy. Lenalidomide (or alternatively also thalidomide) can therefore be used as second-line therapy if bortezomib therapy proves unsuccessful, with the possibility of achieving a complete remission. The increase in the number of complete remissions brought about by bortezomib therapies in patients with AL amyloidosis poses a question about which treatment should be used for younger patients with only moderate damage to their body, i.e. high-dose chemotherapy with autologous hematopoietic cell transplantation or combined treatment with bortezomib. Additional comparative studies are required to be able to answer that question and determine which of the aforesaid therapy modalities is optimal. A question still remains whether the increase in the number of complete remissions due to bortezomib will also bring about longer survival comparable to the results of high-dose chemotherapy treatment with autologous hematopoietic cell transplantation.

High-dose chemotherapy can be defined as utilization of cytotoxic drug doses that produce bone marrow ablation. Transfusion of autologous graft serves as rescue from otherwise fatal myelotoxicity. Immune reaction of graft versus tumor that lowers relapse rates of malignant disease becomes an important contribution of allogeneic hematopoietic stem cell transplantation. New reduced intensity conditioning regimens with lower initial cytotoxicity rely on this immune effect with the potential of additional elimination of remaining cancer cells. Decreased toxicity of these regimens enables treatment of patients with comorbidity and/or in higher age.

The last decade has witnessed an expansion of the arsenal of new immunosuppressive agents to include several novel drugs and antibodies. The main indication of all these immunosuppressive agents is organ transplantation. In terms of its action, tacrolimus resembles cyclosporin A and is employed as the mainstay immunosuppressant or for what is referred to as rescue therapy in refractory rejection. Mycophenolate mofetil is an anti-metabolite replacing azathioprine in immunosuppressive protocols. Sirolimus is an agent for prophylactic use, either as part of a cyclosporin-based regimen to enhance the effect of cyclosporin or as an alternative of non-nephrotoxic immunosuppression to cyclosporin-based regimens; its indications are still being specified. Gusperimus could be used for anti-rejection therapy; however, it is not being used in this country as yet. Recently, two monoclonal antibodies against the IL-2 receptor, chimeric basiliximab and humanized daclizumab, have been employed. Both agents are of non-depletion type and are indicated for induction therapy in the early post-transplant period.

Multiple myeloma is the second most common hematological disease caused by clonal proliferation of B cells. Evaluation of number of plasmocytes in the bone marrow is still one of the basic diagnostic criteria. The aim of this study was to verify if this evaluation has prognostic value even in the era of new drugs.Two groups of MM patients were enrolled in this study. The group T - 45 newly diagnosed MM patients who underwent treatment with thalidomide. Group B - 86 patients in first relapse of MM without autologous transplantation of bone marrow that were treated with thalidomide and bortezomib in various combinations. Percentage of subtypes of plasmocytes in the bone marrow was evaluated based on progressive analysis of nucleus, chromatin and nucleo-cellular ratio (N/C).Mature plasma cells were found in 53.3% (group T) and 53.5% (group B) of patients; proplasmocytes I were found in 22.2% (group T) and 24.4% (group B) of patients; proplasmocytes II were found in 22.2% (group T) and 22.1% (group B) of patients and plasmablasts in 1% (group T) and 0% (group B). Patients who reached treatment response after first treatment had statistically significant number of proplasmocytes II when compared to group without treatment response (median 37% vs. 11%, p = 0.033). Group B patients with mature plasmocytes below 10% had significantly shorter overall survival than other patients when comparison of quartiles was performed. Group B patients with higher infiltration of proplasmocytes I than median of 15% had lower overall survival (median 50.3 months vs. 74.9 months, p = 0,024); the same was true for evaluation of proplasmocytes II (median OS 41.3 months vs. 74.9 months, p = 0,011).Numerical evaluations of plasma cells in the bone marrow remain basic diagnostic criteria of MM even in the era of new genomics analyses. More precise morphological evaluation of 8 subtypes of plasma cells brings important prognostic information that is necessary for new protocols for immunomodulatory drugs and proteasome inhibitors.

Immunosuppressive therapy is crucial for successful kidney transplantation. Induction, antirejection and maintenance immunosuppressive therapy are basic types of immunosuppressive therapy. Base of maintenance immunosuppressive therapy are corticoids + tacrolimus + mycofenolate mofetil. Short and long-term adverse effects are present. Drug interaction with macrolids and antimycotics are substantial. Cooperation between transplantologist and other specialists are crucial for adequate immunosuppressive therapy actualization. Lack of correlation and communication may lead to irrecoverable damage to transplanted kidney.

Myasthenia gravis is very rare autoimmune disease of neuromuscular junction, which presents as a weakness and increased fatiquability of striated muscles. Formerly, myasthenia was largely constraining disease and often ended by death. Recently, advanced diagnostic methods and variety of therapeutic options allow the full compensation of the disease and the quality of patient life is restored. In this review, the methods used during the myasthenia treatment along with the description of the disease itself were detailed.

Venous and arterial graft usage in vascular reconstructions was re-discovered in connection with organ transplantation development. Allografts are employed in many clinics, however, uniform opinion on the use of immunosuppression after the procedure of venous graft transfer from a cadaveric donor, is still lacking.The authors present their own group of patients who underwent vascular reconstructions, and in whom allogenic vein was used. The majority of indications for bypass procedures resulted from critical limb ischemia. Immunosuppressive medication was administered during the vascular procedure and, over the past several years, it purely consisted of tacrolimus monotherapy.In the group of 101 patients, no serious complications due to adverse effects of immunosuppression therapy were recorded.

Between April 1995 and November 2005, 500 liver transplantations were performed in 476 patients of age from 3, till 70, at the Transplantation center of the Institute of Clinical and Experimental Medicine (IKEM) in Prague. The most common indications for liver transplantation were alcoholic liver cirrhosis (23%), hepatitis C cirrhosis (17%), and cholestatic cirrhosis (PBC and PSC, 9% each). Mean MELD score of recipients at the transplantation was 15-18 for each year of transplantation. Ten-years patient survival was 79.1 +/- 2.2%, and graft survival 74.1 +/- 2.1% respectively. Best patient and graft survival was achieved among patients transplanted for autoimmune liver diseases, the worst in group of patients with alcoholic cirrhosis. Malignancies were the most common cause of death during the period of follow-up (17 patients).Patients were followed longitudinally at the Department of hepatogastroenterology IKEM according to prospective protocol included protocol biopsies. Hypertension (in 71% of recipients), and overweight or obesity (in 56.3%), were the most prevalent medical complications among long-term survivors. Diabetes was found in 28.6%, of which 14.7% was de-nove diabetes after transplantation. Renal insufficiency (S-creatinin150 micromol/l) was present in 61 of 348 (17.6%) survivors. Out of these, 16 needed chronic hemodialysis, and 12 underwent kidney transplantation subsequently. Protocol biopsy at 5 years after transplantation was evaluated in a sample of 102 unselected liver transplant recipients. Normal liver was found in 4% of recipients, minor non-specific changes in 36% of them. Disease recurrence was present in all of 16 recipients transplanted for HCV cirrhosis, in one third of them graft cirrhosis was already present. Disease recurrence was found in patients transplanted for autoimmune disease frequently, PBC in 40%, PSC in 25%, and autoimmune hepatitis in 60% of recipients. Graft steatosis greater than 33% was present in 13% of recipients.Liver transplantation is highly effective method of treatment of end stage liver disease. Despite frequent medical complications, and disease recurrence on histological examination almost 80% of recipients transplanted in the liver transplantation program in IKEM survived more than 10 years after procedure. The survival achieved was far above that of the European liver transplant registry.

Transplantation of the small intestine is a standard treatment method in patients with small intestinal failures. The aim of this study was to master the surgical technique, optimalize immunosuppression regimes, diagnose acute cellular graft rejection based on cellular and humoral indicators.The authors performed a total of 43 transplantation procedures in pigs. The first, surgical part of the experiment was aimed at mastering two principal methods of vascular anastomosis- firstly, connecting the graft with mesenteric vessels (Group n1 = 18) and secondly, connecting the graft with the aorta and the inferior vena cava (Group n2 = 25). The second part of the experiment included assessment of rejection changes in various immunosuppression regimes. Only animals who did not die because of a technical failure of the procedure or due to internal reasons (n = 24) were assessed. The study animals were assigned to four groups (A (n = 3)--autotransplantation, without immunosuppresion; B (n = 7) and C (n = 8)--allotransplantation with immunosuppression using tacrolimus, resp. in a combination with sirolimus; D (n = 6)--allotransplantation without immunosuppression. Rejection was diagnosed based on histological examination of the grafts@ biopsy samples. Plasmatic citruline was used as a non-invasive humoral indicator of the graft impairment.Procedural complications were observed in 12 (67%) study animals from the first group, and in 3 (12%) animals from the second group. In the assessment of rejection changes, the longest survival was observed with autotransplantations, the shortest survival period was shown with allotransplantations without immunosuppression. No significant survival differences were demonstrated between the both treated groups. (p0.05). Group C showed lower rates of cellular rejections, compared to Group B and D.During the experiment, the authors managed to master the graft collection, as well as the transplantation technique. Lower rates of surgical complications were observed when the graft was supplied by the central vascular system. No significant differencies were observed between the tacrolimus monoterapy regimen and the combination therapy with sirolimus. Histological examination is the golden standard for the cellular rejection diagnostics. Plasmatic citruline has no signifiance in the rejection assessment.

Ischemia reperfusion injury (IRI) represents a serious problem of transplanted kidneys from a non-heart-beating donor (NHBD). It is probably the main cause of primary a function or delayed graft function. The aim of the experimental study was to demonstrate on an experimental model the possibilities of reduction of IRI by intravenous application of antioxidants or immunosuppressives to the recipient before the kidney transplantation.Piglets weighing between 20-25 kg were used (N = 45) for the experiment. Intravenous application of multivitamins (GI) and a combination of immunosuppressives (GII) was tested one hour before the kidney transplantation from the NHBD. As a control a group (GIII) with simple NHBD modelling was used. At intervals of 0, 20, 60 and 120 minutes after the kidney transplantation, plasma levels of malondiadehyde (MDA) and reduced glutathione (GSH) were assessed. Before and 120 minutes after transplantation tissue concentrations of both factors were assessed in the transplanted kidney.A permanent increase in MDA plasma concentrations occurred in GIII. In GI and GII, after a temporary increase of MDA plasma levels in the first 20 minutes after reperfusion, there was their permanent decrease then. (p0.05, resp. p0.01). The differences in the MDA plasma levels of GI and GII groups did not reach statistical significance. The both groups differed from GIII (p0.001). GSH plasma levels and also tissue concentrations of MDA and GSH were not statistically significant in any group in the course of the experiment.Intravenous application of multivitamins or immunosuppressives before kidney transplantation could have a significant influence on the immediate function of transplanted kidneys from a NHBD.

The calcineurin inhibitors cyclosporine (CsA) and tacrolimus (Tac) are widely used in the prevention of acute rejection after solid organ transplantation. However, their clinical use is associated with many adverse reactions. The calcineurin inhibitors CsA and Tac have a narrow therapeutic index and show highly variable pharmacokinetics. The low CsA and Tac bioavailability has been attributed to interindividual differences in the expression of the metabolizing enzyme cytochrome P450 3A. The genes for CYP3A4 and 3A5 undergo genetic polymorphism. The results of many studies focusing on the impact of CYP 3A polymorphism on CsA and Tac pharmacokinetics are clear with Tac, where an association between CYP 3A polymorphism and the pharmacokinetic consequences has been shown. However, the results with CsA are controversial.

Thalidomide is one of the drugs which are newly used in the therapy of multiple myeloma. Its immunomodulating action and a number of additional effects have been proven in the treatment of advanced and refractory stage of the disease. However, the best dosing scheme has not yet been discovered and is the subject of research in a number of clinical studies today.On a retrospective basis, we evaluated results for 59 patients with multiple myeloma who were treated with thalidomide in our facility (median dose of 100 mg), in monotherapy or in combination with corticosteroids, between 2000 and 2005. The objective was to determine the percentage of responses to treatment in patients at different stages of the disease. Response to treatment was evaluated in accordance with EBMT standards.Thalidomide was used as 2nd line therapy (1st relapse or primarily resistant disease) in 59% of cases (35 patients), and as 3rd line therapy (2nd relapse) in 37 % of cases (22 patients). 2 patients were receiving thalidomide as 4th line therapy. None of the patients had taken thalidomide as part of previous treatment. The response rate at 1st relapse (CR - complete remission, PR - partial remission, MR - minimum response) was 60% (21 patients), of which CR was recorded in 2 patients (6%), PR was recorded in 12 patients (35%) and MR in 6 patients (17%). The response rate at 2nd relapse was 45% (10 patients), of which CR was recorded in 3 patients (14%), PR in 1 patient (5%) and MR in 5 patients (23%). Even though we did not record any statistically significant difference in the response of the evaluated group of patients to the treatment with thalidomide at 1st and 2nd relapse, a higher percentage or progression during treatment (32% vs. 14%) was observed in patients at 2nd relapse. 2 patients treated with thalidomide at 3rd relapse did not have a satisfactory response to the treatment (progression or short stabilisation of the disease with subsequent progression). Only 3 patients (5%) of the evaluated group had to discontinue the treatment due to severe adverse events (neuropathy, allergic reaction, leukopenia). The follow up time for Thalidomide therapy ranged between 3 and 62 months for both groups (with a median of 10 months) and spanned from 3 to 60 months at 1st relapse (median of 12 months) and from 3 to 57 months at 2nd relapse (median of 6 months). No statistically significant differences were observed between the 1st and 2nd relapse groups of patients in terms of response rates or length of effect.Thalidomide is highly efficient in the treatment of multiple myeloma. The results of study document effectiveness of thalidomide regardless of the disease stage. Comparison of study data with the results of other studies shows that the effectiveness of lower doses we used is comparable with that of higher doses. The fact that lower doses of thalidomide reduce the incidence of adverse events is a clear advantage.

To evaluate our experience with the diagnosis and the treatment of the TINU syndrome. The term TINU syndrome means the intraocular inflammation occurring in association with tubulointerstitial nephritis. The predominance of younger females was established. The uveitis is frequently chronic, moderate, and bilateral. The treatment with immunosuppressive drugs often has positive clinical response.A retrospective study.Five patients, 4 women and 1 man, have been examined and treated for the TINU syndrome in our Department for Diagnosis and Treatment of Uveitis. The age ranged from 8 to 62 years. The treatment with immunosuppressive drugs caused reduction of the inflammatory reaction and visual acuity improvement.Immunosuppressive drugs were effective in all of our patients suffering from the TINU syndrome. The cooperation between ophthalmologist and nephrologist is crucial for the effective control of the disease activity and for drug regimen optimization.

Pemhigus vulgaris is an autoimmune bullous disease of the integument. When not treated, it has a high mortality, the treatment with corticosteroids and immunosuppressives has serious side effects. Our casuistry gives a case of patients with histologically verified diagnosis of pemphigus vulgaris. In this case the stabilization of the disease was difficult and side effects of the combined immunosuppressive therapy developed very early.

Improvements in immunosuppressive therapy during the past decade brought about improvements of the long term tolerance of organ allografts. However, the long-term immunosuppressive therapy has an important limitation, because it can increase the risk of cardivascular diseases, infections and tumors. As compared with age-matched healthy population, organ-transplant recipients have an increased incidence of tumors.

To inform about the first own experiences and to present opinion on leading pregnancy and delivery after a combined pancreas and kidney transplantation.Case report and review article.Department of Obstetric and Gynecology, 1st Medical Faculty of the Charles University and General Faculty Hospital, Prague.Pregnancies and deliveries after the transplantation of solid organs are not common. Mostly there are experiences with women after kidney transplantation, smaller or no experiences are with women after transplantation of other solid organs. About 25 pancreas transplantation per year are performed in the Czech republic. Two women after the combined kidney and pancreas transplantation were the first in Czech republic to get pregnant spontaneously and delivered by using a chronic immunosupressive. therapy (Prograf, Imuran, Prednison) in 2002 and 2003. These single pregnancies were led as a high-risk pregnancy in Regional Perinatology Center in collaboration with Transplant and Diabetic Center. Both pregnancies were termined from the obstetrical indication before the term by cesarean section. Both children were healthy. The pregnancy of both patients has not affected the function of the transplanted organs and development of both children has been normal.

Intestinal transplantation is the logical alternative to definitive total parenteral nutrition in patients with chronic intestinal failure. It has become a lifesaving procedure for patients with intestinal failure who cannot be treated using conventional therapies. In children (over 50% of the recipients) indications include short gut syndrome, primary disorders of intestinal motility and mucosal diseases. In adults, the major indication for intestinal transplantation is inadaptable short bowel syndrome after total or subtotal resection. Patients with irreversible intestinal failure and total parenteral nutrition dependency without consistent liver disease must be considered as candidates for isolated small bowel transplantation. Patients with irreversible intestinal failure and end-stage liver diseases are candidates for lifesaving procedure such as combined liver-small bowel transplantation. The appropriate timing for transplantation remains vague. Advanced disease has further consequences because a considerable number of patients may die of progressive liver failure or infection before suitable organs are available. Candidates for intestinal transplantation should be assessed early and should undergo transplantation.

The first succesful liver transplantation was made in USA in 1967. These operations had been made only in few centres in the world until the 80-ies of the last century and the results were not so good. However, along with the development of surgical techniques, immunosuppression and postoperational care the results of these operations significantly improved and their amount increased. The liver transplantation was declared the clinical therapy in USA in 1983. In the same year there was made a succesful liver transplantation in Czech republic too. Nowadays there is annually made approximately 10,000 such operations worldwide. During the last decade it is also in Czech republic where the liver transplantation has become an available therapeutic method. There are two workplaces (CKTCH Brno and IKEM Prague) where 70 such operations are made every year. The results of one-year survival are more than 90% and the long-term results and the quality of life of the patients are also very good. The liver transplantation has experienced a dynamic development in the 90-ies of the 20th century and at the edge of the millenium. There were made significant changes in the field of indications and contraindications for transplantation and immunosuppressive therapy. There developed a brand new surgical techniques making possible to use the organs of the donors who are too big, so-called reduction of the implants. Another option constitute so-called split operations when one implant may be divided into left and right lobes and thus each of them may be used separately for the two donees. Due to the significant regeneration ability of the liver tissue it is possible to make the collection of the parts of the liver from the living donor. According to the statistics of the european countries the optimal need should be 10 transplantations/1 million of inhabitants per year. The difference between the need and the real amount of operations in our country is not given by the disability of the transplantation centres to make these operations but by the fact that many suitable patients are not offered this therapeutic modality at all.

In a group of patients after transplantation of the kidney with stabilized graft function treated by Consupren sol. combined with prednisone and azathioprin in 20 patients (group A) Consupren sol. was replaced by Consupren S capsules, in 17 patients (group B) Consupren sol. therapy proceeded without any change. To maintain the cyclosporin blood concentration within the therapeutic range it was necessary after the change of drug form in group A to adjust the dosage of the drug in 12 patients of group A while in group B only in one patient (p0.01). The mean doses and levels of Cy-A however did not change significantly during the three-month investigation period in the two groups and and the bioequivalence of the two preparations was evident. Conversion from Consupren sol. to Consupren S capsules is not associated with the risk of rejection or undesirable effects. It can be implemented at a ratio of 1:1 or 1: the closest dose divisible by 25 (the smallest capsules are 25 mg) and after conversion a check-up or possible modification of the dose is necessary.

Cyclosporine A (CyA), tacrolimus (FK 506), and mycophenolic acid are routinely utilised immunosuppressive drugs used in the prevention of allograft rejection and the treatment of several autoimmune diseases. The monitoring of CyA blood levels plays the most important role to individualize the dosage regiment and to minimize acute rejection risk and drug toxicity. Inadequate low CyA doses and levels may result in the rejection of transplanted organs. Toxic levels of CyA are associated with many serious side effects, including nephrotoxicity, hepatotoxicity, and a range of other complications. In the period of 1999-2002, 12,859 analyses of whole blood CyA levels were performed at our Department of Clinical Biochemistry. The aim of the present paper is to establish a new monitoring strategy of CyA that consists in the use of a single sampling point at 2 hours postdose and the estimation of blood concentration (C2). For the transplant patient, C2 monitoring is a significantly much better predictor of drug exposition and pharmacokinetic estimation than the trough concentration monitoring before the next dose (C0) used until now. The C2 monitoring strategy reduces the incidence and severity of both acute organ rejection and cyclosporine A toxicity.