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Biomedical subjects

K Mucha

Publications and source records attributed to K Mucha.

At least 19 recordsLinked to original sources
PubMed2004

Proteolytic enzymes activities in patients after myocardial infarction correlate with serum concentration of TGF-beta.

Myocardial infarction (MI) is caused by occlusion of coronary artery and insufficient oxygen supply to a certain area of myocardium. Its necrosis appears as a result of MI. The process of tissue repair after MI is very complicated and it is influenced by numerous factors, including growth factors and proteolytic enzymes. The aim of the study was to determine serum transforming growth factor beta (TGF-beta) concentration on day 2 and 7 after MI and to asses the relationship of this growth factor with serum proteolytic activity of collagenase and elastase. In addition, the effect of fibrynolytic treatment on these factors was evaluated. About 100 patients with MI were enrolled to the study. The control group consisted of 50 healthy individuals. We observed that TGF-beta1 concentration correlated positively with collagenase activity on the second day after MI and that it also correlated positively with elastase activity on day 2 and 7 after MI. Moreover, treatment with streptokinase (SK) caused a significant increase of TGF-beta serum concentration. Our data indicate that TGF-beta1 may be one of the factors involved in tissue repair process after MI. Its effect seems to be mediated by collagenase and elastase and may change with the time that elapsed after MI.

Adult↗
PubMed2003

Effect of immunosuppressive regimen on acute rejection and liver graft function.

Despite the use of modern immunosuppressive drugs, acute liver rejection (AR) continues to affect up to 70% of transplant recipients. The aim of this retrospective study was to assess the incidence of acute rejection episodes in patients treated with different immunosuppressive protocols. In our series, 37.3% of patients developed a clinical episode of AR. Analysis of immunosuppression has shown that the most effective immunosuppressive protocols, with regard to prevention of AR, include: antibody anti-IL-2R (anti-IL-2R) + tacrolimus (Tac) + mycophenolate mofetil (MMF) + prednisolone (Pred); anti-IL-2R + tacrolimus (Tac) + Pred; or Tac + Pred (25% vs 28.6% vs 30.4%, respectively). The highest rate of AR (66.6%) was observed among patients with anti-IL-2R and Tac but no steroid treatment, mostly (77.7%) in the initial period after liver transplantation. There were no statistical differences in liver function tests between the group treated with a CsA-based versus a Tac-based therapy. Strong immunosuppression contributed to a relatively low incidence of clinical AR in our series. The lowest rate of AR was observed among patients treated with anti-IL-2R antibody. Tac, and Pred. Deprivation of steroids in the early phase after liver transplantation substantially increased the risk of acute rejection episodes despite the use of anti-CD25. There were no statistically significant differences in liver function tests among those treated with Tac versus CsA in the short-term follow-up.

Acute Disease↗
PubMed2003

Acute liver transplant rejection: incidence and the role of high-doses steroids.

The aim of this study was to assess the incidence of acute rejection (AR), and the efficacy of high doses of steroids during induction of immunosuppression for AR treatment. Fifty-five patients (33.5%) experienced AR episodes in our series; but, there were no deaths or retransplantations related to AR. The median time from liver transplantation to AR was 18.5 days (range, 2-351 days). In the group with the initial dose of methylprednisolone (MP) </=0.75 g, AR occurred in 32.9% of patients; and in the group with higher dose of MP, 43.6% (P > 0.05). After 1-year observation, liver function tests were similar in both AR and non-AR groups. The only biochemical parameter that was significantly lower in the non-AR group was the aspartate aminotransferase (AST). Liver function tests determined after 1-year follow-up were not significantly different between the groups with AR treated with doses of MP lower versus higher than 1.25 g. However, liver function tests in the group treated for AR with higher doses of MP were slightly better than in the remaining subjects. Recurrence of AR occurred in 5 cases in the group with lower doses of MP (</=1.25 g), and in 2 cases in the group with higher doses of MP (>1.25 g). A relatively low dose of MP was effective to treat AR. The tendency of AR patients treated with higher dose of MP to display better liver function needs further investigation. However, AR does not seem to affect later liver function.

Acute Disease↗
PubMed2003

Cytomegalovirus infection as a common complication following liver transplantation.

The aim of our study was to assess the incidence course, influence on liver function, diagnostic methods, prophylaxis of, and cost treatment effectiveness of CMV infection among 123 consecutive liver transplant recipients. All patients received immunoglobulin and parenterall gancyclovir as prophylaxis. CMV IgM and IgG antibodies were determined using an ELISA method. Thirty seven patients (30.0%) developed CMV infection. Main indications for primary LTX were: immune liver disease (n = 22), viral hepatitis (n = 5), and other (n = 10). CMV infection occurred between the days 5 and 416. Ten patients (27.0%) developed more than one infection (52 infections in total). Asymptomatic CMV infection was diagnosed in six cases (16.2%), CMV syndrome in 11 cases (29.7%), and hepatitis in 35 cases. All patients were treated with gancyclovir and immunoglobulin (18 cases). The intensity of infection was mild or moderate. There was no case of pneumonia or neurological disease, nor the need to use foscarnet. The correlations between the incidence of CMV infection and acute rejection, tacrolimus versus cyclosporine regimens, dual versus triple immunosupressive schemes were not statistically significant, whereas anti-IL-2R-ab antibodies markedly reduced the incidence of CMV infection (P <.05). The values of CMV IgM significantly differred before/during infection (P <.001) and before/after infection (P <.05). In conclusion, prophylaxis and antiviral treatment result in a mild or moderate intensity of CMV infection with acceptable costs. Among immunosuppressive drugs, only anti-IL-2Rab was proved to significantly reduce the incidence of CMV.

Antibodies, Viral↗
PubMed2003

36-month follow-up of 75 renal allograft recipients treated with steroids, tacrolimus, and azathioprine or mycophenolate mofetil.

OBJECTIVES: The aim of this retrospective study was to assess the incidence of acute rejection episodes (AR), diabetes mellitus (DM), and serum creatinine (SCr) among renal transplant recipients treated with tacrolimus (Tac), steroids (S), and mycophenolate mofetil (MMF) or azathioprine (Aza). METHODS: Seventy-five renal allograft recipients enrolled in the COSTAMP study were followed for a period of 3 years. Patients were randomized to receive either Tac and MMF (n = 41) or Tac and Aza (n = 34) concomitantly with steroids. Follow-up assessments were performed at 3, 6, 12, 24, and 36 months. RESULTS: Patient survival at month 36 was 91.18% in the Tac/Aza/S group and 97.56% in the Tac/MMF/S group. Graft survival at month 36 was 82.35% and 85.37%, respectively. During the study period, 22 cases of biopsy-proven AR were diagnosed in 17 patients (22.6%). After 36 months the total number of AR was 11 in the Aza-treated group (32.4%) and 11 in the MMF-treated group (26.8%). DM was diagnosed de novo in 17 individuals (22.6%). During 36 months, 10 patients from Aza-treated group (29.4%) and seven from MMF-treated group developed DM (17.1%). Serum creatinine values were not significantly different in both arms of the study. Comparison of arterial blood pressure and total cholesterol revealed no significant changes in any of the studied groups. CONCLUSIONS: We conclude that combinations of steroids, tacrolimus, and azathioprine or MMF provide good results with regard to renal function.

Adrenal Cortex Hormones↗
PubMed2003

The impact of experience of a transplantation center on the outcomes of orthotopic liver transplantation.

The so-called learning factor has been disregarded for many years in analyzing the causes of surgical complications and post-operative mortality; it is also the case for OLT. In our center until April 2003, 209 OLT were performed in 196 patients. We evaluated the impact of experience of the transplantation team on the outcomes of liver transplantation. Thirty-four patients died (mortality rate, 16%) and 1-year survival rate, 64%. Mortality rates varied during different periods of observation due to increasing experience of the transplantation team. The causes of mortality were assessed for a series of 34 patients: it was 75% at the beginning of transplantation procedures while recent deaths have not recently exceeded 10% of cases.

Gallbladder Diseases↗
PubMed2003

Anti-CD25 and tacrolimus therapy may not prevent early primary biliary cirrhosis recurrence after liver transplantation: two case reports.

Primary biliary cirrhosis (PBC) is an immune-mediated disorder of unknown cause characterized by progressive destruction of intrahepatic bile ducts and the presence of antimitochondrial antibodies. There is no known cure for PBC, and treatment generally includes various combinations of ursodeoxycholic acid and immunosuppressive agents. However, in most patients with end-stage PBC, liver transplantation offers a good quality of life. Recurrent PBC after transplantation is controversial, because most patients with suspected recurrent disease are asymptomatic. Antimitochondrial antibodies frequently persist and do not correlate with disease recurrence. However, most studies support disease recurrence within the graft. The effects of immunosuppression may modify or delay disease expression within the graft. If PBC recurs, intermediate-term patient and graft survivals are excellent, but the long-term outcome remains unknown. Many immunosuppressive agents have been studied with regard to their anti-recurrence properties; however, no standard therapy has been established for this group of patients. In this study we present two patients transplanted for PBC who displayed early recurrence of disease confirmed by liver biopsy and elevated serum AMA. Both individuals received the same immunosuppressive regimen. The data suggest that two doses of daclizumab and tacrolimus monotherapy in the early posttransplant period is insufficient to prevent recurrence of PBC. Addition of glucocorticoids may have beneficial effects in these patients.

Adult↗
PubMed2000

Interleukin 12 and indomethacin exert a synergistic, angiogenesis-dependent antitumor activity in mice.

Nonsteroidal anti-inflammatory drugs have been shown to reduce the incidence and mortality from colorectal cancer. It has recently been demonstrated that these drugs are capable of suppressing the production of pro-angiogenic factors from tumor cells. The mechanisms of antitumor action of interleukin 12 include the enforced secretion of anti-angiogenic factors and stimulation of antitumor immunity. Therefore, we hypothesized that the combination of a model nonsteroidal anti-inflammatory drug--indomethacin and interleukin 12--would result in enhanced angiogenesis-dependent antitumor effects against a colon-26 carcinoma cells transplanted into syngeneic mice. As expected the combined administration of both agents simultaneously resulted in a strengthened antitumor activity that was manifested as a retardation of tumor growth and prolongation of mouse survival. Importantly some mice were completely cured after the combined treatment. As administration of interleukin 12 and indomethacin resulted in enhanced inhibition of angiogenesis it seems possible that prevention of new blood vessel formation is one of the mechanisms responsible for the observed antitumor effects.

Animals↗
PubMed1999

Potentiation of antitumor effects of IL-12 in combination with paclitaxel in murine melanoma model in vivo.

The early clinical trials with interleukin-12 (IL-12) have demonstrated substantial toxicity of this cytokine. One way to resolve this problem would be to find other antitumor agents, e.g. chemotherapeutics, synergistically interacting with IL-12. However, analysis of the recent reports on this topic leads to the conclusion that the antitumor effects achieved in such combination treatments are dependent not only on the drug applied but also on the tumor model used. We described previously lack of the potentiation of antitumor effects in combination treatment with IL-12 and paclitaxel in a murine leukemia L1210 model. We investigated whether such treatment could bring therapeutical benefit by using the murine melanoma MmB16 model. significant potentiation of antitumor effects in combination treatment with IL-12 and paclitaxel was observed. These results suggest that combination of IL-12 and paclitaxel could be beneficial in the treatment of certain types of tumors.

Animals↗
PubMedDate not supplied

Posttransplant lymphoproliferative disorder of the lung in a renal transplant recipient treated successfully with surgery.

Posttransplant lymphoproliferative disorders (PTLDs) are a heterogeneous group of lymphoid diseases that occur after solid organ and bone marrow transplantation. Lung-located PTLD has been reported in recipients of the heart, cord blood stem cells, lungs, and bone marrow transplants, but only four cases were reported previously after kidney transplantation. Thoracic location of PTLD must be regarded as an especially dangerous complication. The pathogenesis, and clinical and histological features of PTLD remain poorly defined but predisposing risk factors are becoming better understood. Namely, Epstein-Barr virus (EBV) and immunosuppressive agents appear to be such risk factors. There has been marginal success in treating PTLD using a number of treatment modalities, including combination chemotherapy with anti-CD20 or high-dose chemotherapy with stem cell rescue. We report a renal allograft recipient transplanted in March 2000, diagnosed with EBV-associated and lung-located PTLD. His initial immunosuppression consisted of tacrolimus, azathioprine, and steroids. Azathioprine was withdrawn in September 2001. In November 2001 a high-resolution computed tomography scan revealed two round masses in the right lung. The patient underwent right thoracotomy and resection of the lower and middle lobe. The diagnosis of PTLD was settled by intraoperative histopathological evaluation. The postoperative histological assessment confirmed the diagnosis and revealed positive staining for EBV. The patient remained in complete remission for 3 years with a well-functioning renal allograft, with current serum creatinine of 1.2 mg%. This case illustrates that the treatment of lung-located PTLD may be successful, but it depends on a combination of prompt diagnosis, reduction of immunosuppression, and of course surgery.

Aged↗
PubMedDate not supplied

Patient with liver epithelioid hemangioendothelioma treated by transplantation: 3 years' observation.

Epithelioid hemangioendothelioma (EHE) is a rare neoplasm of vascular origin, but unknown etiology that occurs in the liver, lungs and other organs. Its hepatic form (HEHE) generally behaves as a low-grade malignant tumor with a slowly progressive phenotype. Surgical resection or liver transplantation (OLT) has been recommended after diagnosis. We present a 30-year-old woman with primary HEHE of the liver treated by OLT in 2002. Her medical history started 3 years prior when an abdominal ultrasound examination revealed multiple focal changes in the liver. The histopathological diagnosis from a needle biopsy was carcinoma cholangiogenes desmoplasticum. For 2 years the patient was treated with chemotherapy combinations. To explain the lack of efficacy of chemotherapy, a laparoscopic biopsy was performed and HEHE diagnosed. Immunohistochemistry revealed positive staining for the factor VIII-related antigens, CD34 and CD31, which have been previously described as HEHE markers. The patient underwent OLT in March 2002. In the first month after OLT, the thyroid stimulating hormone concentration was elevated but they continuously decreased from 11.4 to 2.4 uIU/mL in May 2002 and thereafter remains normal. After 3 years observation the patient presented with good liver function and no signs of tumor recurrence. We concluded that immunohistochemical staining for characteristic endothelial cell markers may facilitate the correct diagnosis of HEHE. After diagnosis, OLT followed by immunosuppressive therapy, consisting of basiliximab, corticoids, low doses of tacrolimus and temporary administration of rapamycin, may be safe and effective. Monitoring of thyroid-stimulating hormone concentrations should be performed in patients with HEHE.

Adult↗
PubMedDate not supplied

How to choose a statin after kidney transplantation: case analyses.

Statins are effective to reduce total cholesterol and low-density lipoprotein fractions in a dose-dependent manner. Moreover, they have an excellent safety profile. Besides cholesterol-lowering properties, statins have additional actions described in the present case report. The diverse effects of these drugs means that many patients with different disease entities, such as cardiovascular diseases, can benefit from their effects. However, the problem of so called "class effect" remains controversial. The question whether each drug within the group is equivalent appears important, as long as statins must be taken long-term and as the therapy affects patient quality of life and survival. To address this question, we present two renal transplant recipients treated with statins. The induction of pharmacokinetic tolerance and damage to hepatic cells during administration of statins is discussed. Presented data suggest that the choice of statin should be based on individual patient requirements and adapted to the individual treatment response.

Adult↗
PubMedDate not supplied

Recurrence of primary sclerosing cholangitis in patients after liver transplantation.

BACKGROUND: Primary sclerosing cholangitis (PSC) is a chronic cholestatic disease that progresses to end-stage liver disease. There are several specific problems related to the posttransplantation period in these patients. The aim of this study was to analyze a single center experience with 17 orthotopic liver transplantations (OLT) due to PSC. PATIENTS AND METHODS: Seventeen patients were included (10 men, 7 women). Actuarial patient and graft survival rates and the incidence of recurrent sclerosing cholangitis were determined at 1, 5, and 7 years. RESULTS: Fifteen patients received single grafts, whereas two patients required retransplants. Patients received either cyclosporine (n = 7) or tacrolimus (n = 10) based immunosuppression. The 1-, 5-, and 7-year patient survival rates were 80%, 60%, and 60%, respectively, whereas the graft survival rates were 88%, 65%, and 65%, respectively. Two patients had cholangiocarcinomas (CCA) diagnosed during OLT; both recurred within 6 months and had a fatal outcome. Two patients (12%) developed recurrent sclerosing cholangitis, as assessed by liver histology and imaging of biliary tree. CONCLUSIONS: Liver transplantation provides good patient and graft survival rates in cases affected with PSC. CCA is associated with poor recipient survival. Recurrent PSC occurs in approximately 12% of cases but does not significantly affect patient survival.

Adult↗