Characteristics of circulating endothelial cells obtained from non-ST-segment elevation myocardial infarction patients with additional diastolic dysfunction of left ventricle observed in echocardiography.

BACKGROUND: Circulating endothelial cells (CEC) may be used to find new strategies for the early di-agnosis of cardiovascular diseases. The major objective of the project is to broaden knowledge of CEC biology by determining their phenotypic characteristics. The additional aim is to clarify whether on the basis of these information it is possible to identify the origin of CEC release (from various cardiovascular compartments). METHODS: Circulating endothelial cells were collected from arterial blood prior to angiography, as well as from arterial and venous blood obtained after angiography/coronary angioplasty, from 18 patients with non-ST-segment elevation myocardial infarction (NSTEMI). CECs were quantified by flow cytometry and defined as Syto16 (dye)+, CD45dim/neg, CD31+ and CD146+. The additional CD36+ was establish as a marker of endothelial cells released from small vessels of the microcirculation. RESULTS: The total number of CECs increased significantly after the percutaneous transluminal coronary angioplasty (PTCA) in the arterial system. Number of CECs isolated at similar time points (after invasive procedure) did not differ significantly between arteries and veins, but the number of CD36+ CECs after coronary angioplasty was significantly higher in the venous system, than in the arterial system. CONCLUSIONS: The number of CD36+ in artery samples obtained after coronary angioplasty (PTCA) had tendency to be decreased (in comparison to the sample obtained before angiography). It was major difference between those who had PTCA performed vs. those who had not.

Predictors of atrial fibrillation early recurrence following cryoballoon ablation of pulmonary veins using statistical assessment and machine learning algorithms.

Inflammation, oxidative stress, myocardial injury biomarkers and clinical parameters (longer AF duration, left atrial enlargement, the metabolic syndrome) are factors commonly related to AF recurrence. This study aims to assess the predictive value of laboratory and clinical parameters responsible for early recurrence of atrial fibrillation (ERAF) following cryoballoon ablation (CBA) using statistical assessment and machine learning algorithms. This study group comprised 118 consecutive patients (mean age, 62.5 ± 7.8 years; women 36%) with paroxysmal (54.1%) and persistent (45.9%) AF who underwent their first pulmonary vein isolation (PVI) performed by CBA (Arctic Front Advance 2nd generation 28 mm). The biomarker concentrations were measured at baseline and after CBA in a 24-h follow-up. ERAF was defined as at least a 30-s episode of arrhythmia registered by a 24 h-Holter monitor within the 3 months following the procedure. 56 clinical, laboratory and procedural variables were collected from each patient. We used two classification algorithms: support vector machines, gradient boosted tree. The synthetic minority over-sampling technique (SMOTE) was used to provide a balanced training data set. Within a period of 3 months 21 patients (17.8%) experienced ERAF. The statistical analysis indicated that the lowered levels of post-ablation TnT (p = 0.043) and CK-MB (p = 0.010) with the TnT elevation (p = 0.044) were the predictors of ERAF following CBA. In addition, diabetes and statin treatment were significantly associated with ERAF after CBA (p < 0.05). The machine learning algorithms confirmed the results obtained in the univariate analysis.

Hemolytic-uremic syndrome: Findings of post-acute renal failure in light and electron microscopy.

The blood count test results of six patients (five male adolescents and one female adult) who were diagnosed with the hemolytic-uremic syndrome are presented. Certain diverse lesions and especially, their different intensity, were observed. They were referred to the clinical process and the time from syndrome occurrence to biopsy.

The presence of thin glomerular basement membranes in various glomerulopathies.

Results of 61 cases of various glomerulopathies with thin glomerular basement membranes are presented. The largest group of 31 cases consisted of mesangial glomerulonephritis. The second largest group consisted of 19 patients with small glomerular lesions described as non-specific. This group stood out in both clinical presentations and in the higher diversity of lesions within the lamina densa of the basement membrane. The results of measurements of the lamina densa in various glomerulopathies were compared to those obtained in control groups consisting of thin basement membrane syndrome and submicroscopic glomerulonephritis.

Clinical pharmacokinetics of clopidogrel and its metabolites in patients with cardiovascular diseases.

BACKGROUND AND OBJECTIVE: Approximately 5-40 % of patients treated with clopidogrel do not display an adequate antiplatelet response. Clopidogrel resistance may be caused by insufficient drug absorption or impaired metabolic activation of the drug. The aim of this study was to evaluate the pharmacokinetics of clopidogrel and its metabolites in plasma samples from patients treated with high and low doses of clopidogrel, to obtain a possible explanation for antiplatelet resistance. METHODS: The study included patients receiving either a single 300 mg loading dose of clopidogrel (n = 17) or a 75 mg dose (n = 45) for at least 7 days before sample collection. The concentrations of clopidogrel and its metabolites-the inactive H3 and the pharmacologically active H4 isomers of the thiol metabolite and the inactive carboxylic acid metabolite-in plasma samples (stabilized with 2-bromo-3'-methoxyacetophenone) from three patients after 300 mg and from 41 patients after 75 mg of the drug were determined using a validated high-performance liquid chromatography method with tandem mass spectrometry. The non-stabilized samples from the remaining patients were analysed using a validated capillary electrophoresis method. The calculated concentrations were used to determine the pharmacokinetic parameters of the analytes. The pharmacodynamic response to clopidogrel treatment, expressed as adenosine diphosphate-induced platelet aggregation, was measured using a Multiplate analyser. RESULTS: The pharmacokinetic parameter values for the H3 and H4 isomers determined in the studied group of patients treated with clopidogrel 75 mg (maximum plasma concentration [C max] 5.29 ± 5.54 and 7.13 ± 6.32 ng/mL for H3 and H4, respectively; area under the plasma concentration-time curve from time zero to time t [AUC t ] 7.37 ± 6.71 and 11.30 ± 9.58 ng·h/mL for H3 and H4, respectively) were lower than those reported in healthy volunteers, according to the literature data. Platelet aggregation measured with a Multiplate analyser ranged between 37 and 747 AU·min. A significant correlation was found between the C max of the active H4 isomer and platelet aggregation (p = 0.025). CONCLUSION: The C max of the active H4 isomer and platelet aggregation measured by the Multiplate analyser may serve as markers of the patient response to clopidogrel therapy.

Ki-67 and p53 expression in ileal pouches.

Development of dysplastic lesions that may potentially lead to cancer is sometimes reported within the ileal pouches. Dysplasia is in turn associated with increased expression of proliferation indices. The goal of this study was to evaluate the mitotic activity and possible expression of p53 in the epithelium within the ileal pouches in patients with chronic ulcerative colitis. The study involved archive material consisting of ileal pouches surgically removed from 17 patients diagnosed with ulcerative colitis. Several specimens were collected from each pouch. The immunohistochemistry (Ki-67 and p53 protein) control group (14 cases) consisted of the resection line specimens of colons removed due to colorectal adenocarcinoma. Intensity of the expression of the markers under study within the inflammatory infiltrates was assessed using a 5-point scale proposed by Berstein et al. Ki-67 expression was observed in all studied patients with marked intensity (Bernstein scale score +3, +4). Protein p53 expression was observed only in eight patients, and was mostly of low intensity (Bernstein scale score +1, +2). Immunohistochemical results confirmed the histopathological results that revealed dysplastic lesions, which are often an indication for radical procedures in ulcerative colitis patients. Our results suggest the usefulness of these examinations, also in the ileal pouch material.

Focal segmental glomerulosclerosis: a diagnostic problem.

Focal segmental glomerulosclerosis (FSGS) is an important clinical problem as it leads to end-stage renal disease. Clinicians have long been able to treat patients with FSGS. Therefore, the demands the clinicians make on pathomorphologists, which include the diagnosis of FSGS at a possibly early stage, are justifiable. However, early diagnosis of FSGS is difficult. The analysis involved 150 cases of FSGS diagnosed between 2003 and 2008. These constitute 14.53% of renal biopsy material of that period. The test material comes from 138 adults and 12 children. The adult group mostly included patients with albuminuria (58 patients) and nephrotic syndrome (36 patients). Smaller groups included patients with albuminuria and hypertension, erythrocyturia and albuminuria, isolated erythrocyturia. The children group mostly included patients with the nephrotic syndrome. Individual patients suffered from isolated albuminuria and erythrocyturia. In both groups, FSGS NOS lesions prevailed. However, FSGS hilar and FSGS tip lesions, as well as completely sclerotized glomeruli were also present. Diverse symptoms of diseases may pose specific difficulties in clinical diagnosis. Similarly, determination of FSGS lesion type may be difficult due to simultaneous presence of different subtypes in the same punctate.

Postinfarction heart failure: surgical and trans-coronary-venous transplantation of autologous myoblasts.

Increasing experimental evidence indicates that skeletal myoblasts can be considered as a possible source of cells for regeneration of contractile performance in chronic postinfarction myocardial injury. In experimental models, the observed functional benefit of transplanting skeletal myoblasts into an area of chronic fibrotic myocardial scar has led to the development of clinical trials to evaluate the potential use of autologous skeletal myoblasts for myocardial regeneration in patients with postinfarction heart failure. We conducted an independent, phase I clinical trial to evaluate myoblast transplantation during coronary artery bypass grafting. In addition, to test whether the effect of transplanted cells on myocardial contractility was independent of revascularization, we performed a clinical study of percutaneous transvenous myoblast transplantation-the POZNAN trial. These trials have shown the feasibility of myoblast transplantation during cardiac surgery and via a percutaneous route, as well as the safety of both procedures when performed with concurrent prophylactic administration of amiodarone. Here, we review the details of our observations from both of these phase I clinical trials in the context of the clinical work in cardiovascular cell transplantation performed by others.