H Zakliczynska

Medical University of Silesia in Katowice, Catowice, Silesian Voivodeship, Poland

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Publications (19)38.16 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: BACKGROUND: Disturbed glucose metabolism, particularly in diabetes type 2 (DM2), may result in advanced glycation end product (AGE) formation. One of the possible targets for this reaction is lipofuscin (LF), an intracytoplasmic garbage presumed to be a marker of physiologic and preterm aging of cells. The study was performed to seek for a relationship between AGE and LF in cardiocytes of the failing hearts. MATERIAL AND METHODS: Archived tissue samples from 136 hearts explanted before transplantation (in 14 pts. with ischemic cardiomyopathy (CM) and DM2; 8 pts. with dilated CM and DM2; 67 non-diabetic pts. with ischemic CM; 47 non-diabetic pts. with dilated CM), 14 autopsy cases with DM2, and 20 heart donors (control group) were involved in the study. Immunohistochemical localization of AGE was applied. The coexistence of lipofuscin and AGE was studied by LF autofluorescence in AGE-positive slides. RESULTS: LF granules inside AGE deposits were present in all studied groups with varying frequencies, but the differences were non-significant. LF granules joined significantly with dispersed patterns of AGE i.e. diffuse and mixed, whereas coincidence of LF and AGE forming granular pattern was rare. CONCLUSIONS: We demonstrate that LF may belong to the components of the AGE deposits. The frequency of this phenomenon is dependent on the AGE dispersion grade, but neither on diabetes nor cardiomyopathy presence.
    Experimental gerontology 09/2012; · 3.34 Impact Factor
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    ABSTRACT: Gingival hyperplasia is a common complication of immunosuppressive therapy with cyclosporine A (CyA). However, the association of CyA with increased tissue concentrations of TGF- β(1), a potential causative factor of hyperplasia, remains unknown. The aim of the study was to assess the impact of TGF- β(1) and IL-2 on the development and maintenance of gingival hyperplasia in patients treated with CyA after orthotopic heart transplantation (OHT). Gingival hyperplasia was indexed in 60 patients, in accordance with McGraw and Potter scale. Patients were divided and comparisons were made among 3 groups: Group A (18 patients; 49.0 ± 12.1 y/o) after OHT with gingival hyperplasia (score 1, 2, 3), Group B (12 patients; 40.0 ± 15.1 y/o) after OHT without gingival hyperplasia (score 0), and Group C - the control group - (30 patients; 42.0 ± 10.8 y/o) with clinically healthy paradentium. Cytokines (TGF- β(1) and IL-2) were marked in gingival tissue homogenate. The concentration of CyA was marked in the patients' blood (Groups A and B). The highest mean concentration of TGF- β(1) was obtained in Group A and the lowest concentration was in the control group. A positive correlation was found between TGF- β(1) in gingival tissue and CyA blood concentration in Groups A and B. TGF- β(1) is associated with gingival hyperplasia in patients treated with CyA after OHT procedure.
    Annals of transplantation: quarterly of the Polish Transplantation Society 06/2012; 17(2):45-52. · 0.82 Impact Factor
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    ABSTRACT: Non-enzymatic coupling of protein and lipid cellular structures with glucose leading to the formation of advanced glycation end products (AGE) plays a role in aging and the development of diabetic complications, but its contribution to myocardial pathology is unclear. We aimed to assess the role of heart failure on AGE formation in patients with or without diabetes mellitus type 2 (DM2). Heart tissue specimens from 136 patients undergoing transplantation were grouped as follows: 14 cases of ischemic cardiomyopathy (ICM) and DM2, 8 cases of dilated cardiomyopathy (DCM) and DM2, 67 cases of ICM without DM2, and 47 cases of DCM without DM2. Fourteen heart samples were from the autopsies of patients with DM2 without heart disease, and 20 heart samples were from organ donors in whom the heart was wasted. AGE deposits were localized immunohistochemically counted using a semiquantitative scale and characterized by their staining pattern. Positive staining was present in all samples from both cardiomyopathy groups with DM2, in 71% of healthy hearts from the DM2 subjects, in 51% of ICM non-diabetic hearts, and in 38% of DCM non-diabetic hearts, and in only 15% of the organ donors. Mixed-diffuse and granular AGE patterns were characteristic for DM2, while a diffuse pattern was more frequently observed in heart failure patients without diabetes. The semiquantitative results supported increased AGE accumulation in patients with DM2 and/or cardiomyopathy. The amount of AGE in cardiomyocytes increases significantly in both diabetes and heart failure, with a staining pattern typical for each condition.
    Annals of transplantation: quarterly of the Polish Transplantation Society 06/2012; 17(2):53-61. · 0.82 Impact Factor
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    ABSTRACT: A pilot study of orthotopic heart transplant (OHT) recipients showed that advanced glycation end-product (AGE) deposits were related to acute rejection episodes among subjects with diabetes mellitus (DM); in contrast, among non-DM patients it was associated with prolonged freedom from coronary artery vasculopathy (CAV). However the number of observations in non-diabetic subjects was low. The aim of the current study was to establish the role of AGEs in late endomyocardial biopsies (EMBs) among a larger group of non-diabetic patients. Elective EMBs were performed at 3 years post OHT in 62 subjects with DM, namely, 57 males and 5 females of overall mean age of 50±8 years versus 92 free of DM, including 79 males and 13 females of mean age 51±13 years. We localized AGEs in myocardial paraffin sections using monoclonal mouse anti-AGE antibodies. The presence of AGEs in cardiomyocytes, stromal cells, capillaries, and arterioles was described with a semiquantitative scale. All-cause deaths, CAV, and CAV-related events were observed in 28% versus 23%, 27% versus 29%, and 15% versus 19% of non-DM versus DM patients (P=NS). The occurrence of AGEs was significantly more frequent among non-DM than DM subjects: cardiocytes, 100% versus 69% (P<.0001); stroma, 54% versus 31% (P=.0037); capillaries, 67% versus 31% (P<.0001); and arterioles, 26% versus 3% (P=.0002; chi-square). Among the DM group, mean EMB score correlated with AGE presence in cardiomyocytes (n=0.29; P<.05, Spearman test) AGE presence had no impact on survival or CAV development. AGE presence was more common in late EMB from non-diabetic than diabetic OHT recipients; they had no impact on survival or CAV in non-diabetic patients.
    Transplantation Proceedings 10/2011; 43(8):3058-60. · 0.95 Impact Factor
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    ABSTRACT: Statins are used in orthotopic heart transplant (OHT) recipients to avoid acute rejection episodes (ARE) during the first year after surgery and coronary vasculopathy (CAV) thereafter as established in prospective randomized trials, yielding the grounds for the universal use of this group of drugs. The aim of the study was to describe the occurrence of dyslipidemias among OHT recipients after introduction of guidelines suggesting the use of statins in all individuals able to tolerate this therapy. Medical records of all OHT recipients undergoing routine clinical checkups between January and June 2010 were screened for the presence of dyslipidemia: total cholesterol>5 mmol/L; low-density lipoprotein (LDL)-cholesterol>3 mmol/L; triglycerides>1.65 mmol/L; high-density lipoprotein (HDL)<1 mmol/L in the serum. The study group consisted of 322 subjects including 265 males and 57 females of overall mean age of 53.6±12 and 7±4 years after OHT. There was coronary artery disease (CAD) before OHT in 113 (35%). The average number of ARE was 1.9±1.9 and CAV was diagnosed in 77 (24%) patients. There were 247 (77%) patients on statins. We analyzed clinical, ultrasound, and biochemical evaluations to characterize subjects with dyslipidemias. At least one dyslipidemia was observed among 212 (66%) including hypercholesterolemia in 121 (38%), high LDL in 135 (42%), hypertriglyceridemia in 110 (34%), and low HDL in 48 (15%) patients. The subjects with dyslipidemia were prone to be older, to have CAD before OHT, and to be hypertensive, overweight, and obese, as well as display an higher HbA1C when diabetic. They were treated less frequently with tacrolimus but showed higher drug levels, and more often were prescribed everolimus. Despite almost universal use of statins, dyslipidemias were present in 2/3 of OHT recipients. It was related to typical atherosclerotic risk factors; however, the influence of immunosuppressants seemed to also be significant.
    Transplantation Proceedings 10/2011; 43(8):3071-3. · 0.95 Impact Factor
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    ABSTRACT: The aim of this retrospective analysis was to assess the influence of rapamycin (RAPA) used perioperatively on surgical complications in heart transplant recipients. The study group consisted of 28 heart transplant recipients (26M/2F, 49.2+/-11 years) receiving 15 mg of RAPA before operation, 10 mg of RAPA on the first postoperative day (POD) and 5 mg daily (n=20) thereafter, or 5 mg daily starting on POD 2 (n=8), until the introduction of cyclosporine-A. A matched historical control group was composed of 28 patients (26M/2F, 49.7+/-9 years) receiving cyclosporine-A from POD 1. We compared a number of surgical complications and reinterventions among groups. Statistical significance was assessed using the chi-square test and the Mann-Whitney U-test. There were 16 (57%) patients in the study group vs. six (21%) in the control group requiring reintervention (p=0.014). Pericardial tamponade decompression was performed in seven (25%) vs. zero patients, and sternum refixation in seven (25%) vs. zero patients (p=0.015). None of the wounds was infected. The overall drainage volume was 4,213+/-5,996 vs. 1,911+/-1,728 mL (p=NS). The frequencies of biopsy-proven rejection and infection were comparable, except lower cytomegalovirus infection rates in the study group: three (11%) vs. 11 (39%) for the control group (p=0.023). The use of RAPA in the perioperative period of heart transplantation increases the risk of surgical wound-healing complications.
    Wound Repair and Regeneration 01/2007; 15(3):316-21. · 2.76 Impact Factor
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    ABSTRACT: Prolonged cold ischemia time (CIT) is one of the most common causes of acute tubular necrosis (ATN) with consequent delayed graft function after kidney transplantation. The aim of the study was to analyze the impact of early donor lymph nodes (LN) procurement in combination with local or central HLA typing on CIT, on donor-recipient HLA mismatches, and on the early results of grafts. Two hundred six cadaveric procedures were performed from 2001 to 2004 including 86 cases out of 119 recipients who were matched locally and 60 cases out of 87 recipients who were matched centrally, wherein LN were obtained before kidney harvest. CIT was significantly shorter when LN were obtained before kidney harvesting both in local (13.6 vs 20.6 hours) and central (20.1 vs 27.7 hours) matching (both P < .001). ATN frequency was significantly lower in patients with LN obtained earlier (27.9%) when matched locally versus (35.0%) when matched centrally. Kidney graft function estimated at 12 months was similar in both groups. CIT longer than 19.5 hours predicted ATN occurrence with 57.7% sensitivity and 66.4% specificity. Local matching resulted in shortening CIT compared to central matching (15.5 vs 22.4 hours); however, the mismatch in HLA class I and HLA class II were significantly worse (HLA A + B 2.76 vs 2.45, HLA DR 1.21 vs 0.82). These discrepancies did not significantly influence the frequency of ATN (36.1% vs 40.0%) or the kidney graft function at 12 months.
    Transplantation Proceedings 01/2006; 38(1):39-41. · 0.95 Impact Factor
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    ABSTRACT: The purpose of this study was to assess the prognostic value of a single IVUS result described by the Stanford scale to predict CAV development. Inclusion criteria were heart transplantation (OHT) before 1997 and at least one IVUS performed before 1998. IVUS studies were performed in 37 patients at 37 +/- 26 months after OHT. Based on the Stanford scale, were divided patients into Four groups: group I (grade 0 or 1): n = 4, 42 +/- 19 years, 2 men/2 women; group II (grade 2): n = 10, 44 +/- 15 years, 9 men/1 woman; group III (grade 3): n = 11, 48 +/- 11 years, 11 men; and group IV (grade 4): n = 12, 46 +/- 8 years, 12 men. We compared the incidence and time of onset of clinically significant CAV, namely significant coronary lesions, myocardial infarction and death caused by CAV. There was no CAV diagnosed in group I. The rates of CAV in coronary angiograms in groups II, III and IV were: 80%, 36%, and 75%, respectively. Significant CAV was found in 30%, 9%, and 50% of patients, respectively. Average times of onset of any CAV in groups II, III and IV were 4.9, 5.6, and 3.3 years, and for significant CAV were 4.1, 3.6, and 5.5 years, respectively. Deaths in groups I to IV were 1, 4, 2, and 5, respectively. CAV was the reason for death in 1 patient from group III, and 3 patients from group IV. Extreme grades on the Stanford scale (0, 1, and 4) describing a single IVUS study in OHT recipients appear useful to stratify patients with the lowest versus the highest risk of CAV development.
    Transplantation Proceedings 04/2005; 37(2):1343-5. · 0.95 Impact Factor
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    ABSTRACT: The purpose of this study was to assess the clinical utility of mycophenolic acid (MPA) trough concentration monitoring in heart transplant recipients. METHODS: We reviewed 456 MPA plasma level measurements (EMIT/Dade-Behring) which were performed in 76 pts. after orthotopic heart transplantation (OHT): 57 M and 21 F, age 41.9 +/- 16, time after OHT (months) 17.6 +/- 24. Daily dose of mycophenolate mofetil (MMF) was 2-3 g before MPA measurement introduction, then it was adjusted to achieve MPA trough levels (TL) of 2-4 microg/ml. Additionally pts. received either cyclosporine-A (CyA) or tacrolimus and prednisone. We analyzed first MPA levels obtained in pts. without previous monitoring, then we looked for a relation between CyA or tacrolimus and MPA level, and finally we checked for a relation between MPA level and the side-effects of MMF RESULTS: In a group of 59 pts. without earlier MPA level monitoring we found that 36 pts. (61%) had MPA level below, 19 pts. (32%) within, and 4 pts. (7%) above target TL. We identified a group of 11 pts. (characterized by unstable CyA TLs and liver impairment) with a significant positive correlation between CyA and MPA level. For the remaining group of pts. we found a non-significant negative correlation between CyA and MPA concentrations. Target MPA TL was achieved in 40% of cases in pts. with CyA TL below 200 ng/ml (Axsym/Abbott), in 40% of cases in pts. with CyA TL 200-300 ng/ml, and in 27% of cases in pts. with CyA TL over 300 ng/ml. There was no correlation between tacrolimus and MPA level. MPA TL over 4 microg/ml occurred in 22% of results from pts. receiving tacrolimus (n=6) and 11% of pts. on CyA (n=17, p = 0.011). 90% of these pts. had symptoms of GI irritation, 33%--leucopoenia, and 14%--anemia. CONCLUSIONS: It is uncommon to achieve MPA TL of 2-4 microg/ml with typical doses of MMF, especially with concomitant high CyA TL. Typical side effects of MMF should be an indication to check MPA TL.
    Annals of transplantation: quarterly of the Polish Transplantation Society 02/2005; 10(2):38-45. · 0.82 Impact Factor
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    ABSTRACT: Transplanted heart coronary artery disease (TxCAD) is the most frequent casue of death occuring > or =5 years after orthotopic heart transplantation (OHT). Considering three basic therapeutic approaches - percutaneous coronary intervention (PCI), surgical revascularisation and retransplantation - PCI seems to be the superior method due to its safety and good short-term results, however, the long-term efficacy of PCI has been less well established. To evaluate long-term results of PCI in the treatment of OHT recipients with TxCAD. The study group consisted of 20 patients (19 males, aged 24-63, median 45.5 years; 14 (70%) had before OHT), who underwent single or multiple PCI of significant coronary lesions, revealed by elective (n=17) or urgent (n=3) coronary angiography (CAG). The overall number of PCI procedures was 26, including 8 with stent implantation. procedures were performed 9-151 (median 61.5) months after OHT. Analysis of PCI results was based on the follow-up CAGs or autopsy in case of death. Follow-up time was 3-90 (median 28) months. At least one CAG was performed in 17 (85%) patients - the overall number of follow-up CAGs was 53. Progression of TxCAD was revealed by 33 (62%) CAGs - the decision to perform subsequent single or multiple PCI was undertaken in 22 (42%) patients. The overall number of re-PCI procedures was 38 (with stent implantation in 11 cases). Out of 38 PCI procedures without stent implantation, significant restenosis was found on control CAG in 16 (42%) patients, and out of 16 PCI with stents -- in 11 (69%) patients, including 8 haemodynamically significant lesions. TxCAD was the cause of 5 out of 9 deaths that occurred during follow-up. PCI is unable to stop TxCAD development in the majority of patients. Stent implantation does not improve long-term results of TxCAD treatment.
    Kardiologia polska 10/2004; 61(10):339-48; discusion 349. · 0.54 Impact Factor
  • Transplantation 01/2004; 78:702-703. · 3.78 Impact Factor
  • Transplantation 01/2004; 78. · 3.78 Impact Factor
  • Transplantation 01/2004; 78. · 3.78 Impact Factor
  • Transplantation 01/2004; 78. · 3.78 Impact Factor
  • Transplantation 01/2004; 78. · 3.78 Impact Factor
  • Transplantation 01/2004; 78. · 3.78 Impact Factor
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    ABSTRACT: A retrospective analysis of all cases when cyclosporine (CyA) was replaced with sirolimus (SIR) to avoid the renal toxicity of CyA late after heart transplant (OHT) was discontinued due to advanced renal impairment in all five heart transplant recipients (four men, 1 women; age 41 years, range 38-45; time after OHT 5 years, range 4-14). The serum creatinine level at the time of SIR introduction, which was 298 micromol/L (range 217-676), had remained stable for the 6 months prior to conversion. Target SIR trough levels were 12-20 ng/mL. In four patients the last dose of CyA was immediately followed by the first dose of SIR, whereas in one patient CyA was tapered gradually in the presence of low-dose SIR. Deterioration of renal function with signs of fluid overload and increased serum creatinine levels (Delta: 77, 33-150 micromol/L) was observed in all patients. Two patients required dialysis during SIR treatment including one case of pulmonary edema requiring emergency hemodialysis. None of four biopsies showed significant rejection. Four patients were converted back to low-dose CyA (including the two patients requiring dialysis during SIR therapy); one was maintained on mycophenolate mofetil. The creatinine level at the time of SIR discontinuation was (range 250-753) micromol/L, 448. Eventually, all patients required dialysis. In conclusion, replacement of cyclosporine with sirolimus in heart transplant recipients with severe renal impairment late after transplantation may accelerate renal failure.
    Transplantation Proceedings 10/2003; 35(6):2331-2. · 0.95 Impact Factor
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    ABSTRACT: Aim of this study was to find features characteristic for steroid resistant cellular rejection (SRR) of the transplanted heart, using phenotypic identification of cells creating infiltrates in endomyocardial biopsies (EMBs) obtained before and after high dose steroids treatment. 146 heart transplant recipients, treated with cyclosporine-A, azathioprine and prednisone, were taken under consideration. EMB results > or = 3A (ISHLT) were considered significant rejection, requiring treatment with 1 g i.v. methylprednizolone for 3 days followed by oral prednisone. SRR was diagnosed in case of increased grade of rejection in control EMB, lack of improvement in 2 consecutive EMBs or increasing hemodynamic compromise. SRR was found in 15 pts. (study group). Control group consisted of remaining 131 pts. Paraffin-embedded blocks containing EMB samples from 9 pts. from study group and randomly chosen 14 pts. from control group were used (2 EMBs per pt.). Significant rejection was present in the first EMB, the second EMB was performed 7 days after beginning of the treatment. In the study group, first 2 EMBs creating a sequence of SRR were analysed. Following antigens were identified: CD45RO (T-cells), CD8 (cytotoxic T-cells), CD20 (B-cells), and CD95 (marker of apoptosis). DR expression and macrophages presence were also quantified. CD45RO was predominant phenotype before and after treatment in both groups. Higher quantity of CD20 cells were observed in study group, however its number increased after treatment in control group. CDB-cells and macrophages were present in low amounts, that did not react to treatment. CD95 positive cells were present only in 3 EMBs. None of above differences was statistically significant. DR expression staining showed no difference either in biopsies taken before steroid treatment or after completing of high dose steroid therapy. Phenotype identification of cells infiltrating myocardium of the transplanted heart was not sufficient to predict or characterise steroid resistant rejection.
    Annals of transplantation: quarterly of the Polish Transplantation Society 02/2003; 8(1):13-8. · 0.82 Impact Factor
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    ABSTRACT: Aim of the study was to assess frequency and risk factors of steroid resistant cellular rejection (SRR) in heart transplant recipients, to determine methods of its treatment, and to evaluate influence of steroid resistant rejection and method of its treatment on short- and long-term results. All pts. received cyclosporine-A, azathioprine and prednisone. Biopsy results > or = 3A (ISHLT) were considered a significant rejection, requiring treatment with 1 g i.v. methylprednizolone for 3 days followed by oral prednisone. SRR was recognized in case of biopsy-proven progression of rejection, lack of improvement in 2 consecutive biopsies, or increasing hemodynamic compromise despite treatment of biopsy-proven rejection. 146 pts. eligible for the study were divided into: study group--15 pts. with SRR (10%), and control group--131 pts. SRR was treated with: cytolytic therapy--ATG (10 pts.), mycophenolate mofetil (3 pts.) or steroids (2 pts.). Number of biopsies > or = 3A, cumulative biopsy score, average biopsy result, effectiveness of SRR treatment, side effects of therapy, and survival were analysed. All parameters characterizing rejection were significantly higher in the study group. No risk factors of SRR were found. In 6 pts. with SRR and hemodynamic compromise (all treated with ATG) improvement was observed in 4 pts, while death occurred in 2 pts. There were no deaths in pts. without hemodynamic compromise--none of 3 methods of treatment was superior, however ATG increased the infection risk. Survival in the 1st year was significantly lower in the study group (67% vs. 89% in the control group). SRR is recognized in about 10% of heart transplant recipients, increasing risk of death in the 1st year after surgery. Cytolytic therapy increases risk of infection, and should be avoided in pts. without hemodynamic compromise.
    Annals of transplantation: quarterly of the Polish Transplantation Society 02/2003; 8(1):25-36. · 0.82 Impact Factor