Left, but not right, ventricular status determines heart failure in adults with Ebstein anomaly - A case-control study based on magnetic resonance.

BACKGROUND: Ebstein anomaly (EA) is a congenital heart defect affecting the right heart. Heart failure (HF) is a significant complication in adults with EA. It may result not only from the right ventricle (RV), but also from the left ventricle (LV) abnormalities. We evaluate the size and function of both ventricles in patients with EA in cardiac magnetic resonance (CMR); to assess their association with the clinical markers of HF. METHODS: Study group: 37 unoperated adults with EA (mean age 43.0 ± 14.4y, 21[56.8%] males). CONTROLS: 25 volunteers (mean age 39.9 ± 10.9y, 15[60%] males). Study protocol included: CMR [ejection fraction (EF), end-diastolic (EDVind) and stroke volumes (SVind) indexed by body surface area]; cardiopulmonary test (peak VO2, %peak VO2, VE/VCO2 slope). RESULTS: Size and systolic function of LV were reduced comparing to the controls [LVEDVind (ml/m2): 63.7(range 38.7-94.2) vs. 79.3(48.7-105.1), p < 0.001; LV SVind (ml/m2): 35.8(22.9-55.1) vs. 49.2(37.8-71.7), p < 0.0001; LVEF(%): 58.3(34-70.5) vs. 62.0(52.0-77.0), p = 0.009]. RV was enlarged comparing to the controls [RVEDVind (ml/m2): 124.3(52.8-378.9) vs. 83.0(64.0-102.0), p < 0.0001) with impaired systolic function (RV SVind (ml/m2): 22.7(11.1-74.1) vs. 48.0(37.8-71.7), p < 0.0001; RVEF(%): 38.0(21.0-66.1) vs. 59.0(49.0-69.0), p < 0.0001). A significant correlation was found between LVEDVind vs. peakVO2 (r = 0.52, p = 0.001); LV SVind vs. peakVO2 (r = 0.47,p = 0.005). There was no correlation between the right ventricular status and exercise capacity. CONCLUSIONS: In adults with Ebstein anomaly the size of left ventricle is reduced, right ventricle is enlarged; the function of both is impaired. Abnormal exercise capacity is associated with left ventricular status. Ventricular interdependence probably plays a role in heart failure pathomechanism.

Psychosocial Late Effects in Adolescent and Young Adult Survivors of Childhood Cancer Diagnosed with Leukemia, Lymphoma, and Central Nervous System Tumor.

Purpose: The prevalence of psychosocial late effects and quality of life in adolescent and young adult (AYA)-aged survivors of pediatric cancer have been studied. Methods: The study was conducted in AYA survivors who had been diagnosed with leukemia, lymphoma, or brain tumor, had completed treatment at least 1 year before the study, and were 15-39 years old at study enrollment. The control group consisted of healthy volunteers. A questionnaire comprised a demographic form, eight questions concerning mental health and the disease, and survey The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30. Controls received a questionnaire without questions concerning an illness. Results: Most of survivors believed that cancer treatment might have a serious influence on their health. Survivors significantly more frequently declared using drugs: neuroleptics, tranquilizers, and antidepressants than controls. Survivors of leukemia demonstrated significantly more problems in cognitive functioning than lymphoma survivors. Females were significantly more disabled in emotional functioning than males. Young adults more often reported dysfunction in emotional functioning compared to adolescents. Survivors who were assessed ≥10 years since therapy reported significantly more disadvantage in social functioning than those assessed <10 years since treatment completion. Survivors reported significantly more disadvantages in social functioning than controls. Allogeneic hematopoietic stem cell transplantation survivors more often suffered cognitive limitations. Irradiated survivors more often attended psychological therapy. Conclusions: Survivors of pediatric cancer are vulnerable to consequences of oncological treatment, making their quality life significantly worse in comparison with healthy controls. They need to be monitored, supported, and educated.

Severity Scores for Ebstein Anomaly: Credibility and Usefulness of Echocardiographic vs Magnetic Resonance Assessments of the Celermajer Index.

BACKGROUND: The severity score of Ebstein anomaly (EA) that corresponds to clinical status is still under research, with the Celermajer index (Cel-ind) being one of those. The agreement between echocardiographic and cardiac magnetic resonance (CMR) assessment of Cel-ind is not known. We determined the agreement between echocardiography- and CMR-derived Cel-ind and its relationship with heart failure markers. METHODS: A total of 37 unoperated adults with EA (mean age, 43.0 ± 14.4 years) underwent echocardiography, CMR, and cardiopulmonary tests. For the Cel-ind, end-diastolic areas in echocardiography or end-diastolic volumes in CMR were used according to the following formula: Cel-ind = (right atrium + atrialized right ventricle)/(functional right ventricle + left atrium + left ventricle). On the basis of this assumption, patients were classified as follows: grade 1 = Cel-ind < 0.5, grade 2 = 0.5 to 0.99, grade 3 = 1.0 to 1.49, grade 4 > 1.5. The agreement between echocardiographic and CMR was determined with the intraclass correlation coefficient or Cohen's kappa (<0.2 poor agreement; 0.2-0.4 fair agreement; 0.4-0.6 moderate agreement; 0.6-0.8 good agreement; 0.8-1.0 very good agreement). RESULTS: The median echoCel-ind was 0.9 (range, 0.4-2.3), and the median cmrCel-ind was 0.7 (range, 0.3-5.3). Grade 1 or 2 was found in 19 patients (51.3%) by echocardiography and in 27 patients (72.9%) by CMR. The agreement between imaging methods was only fair (kappa = 0.39, P = 0.002) for the 4-grade classification and moderate (intra-class correlation coefficient = 0.43; 95% confidence interval, 0.13-0.66) for Cel-ind calculation. Significant correlations between Cel-ind in CMR and cardiopulmonary parameters were found (for peak oxygen uptake: R = -0.35, P = 0.034; for the ventilation/carbon dioxide slope: R = 0.46, P = 0.005). Neither of them correlated with echocardiographic severity score. CONCLUSIONS: The agreement between echocardiographic and CMR assessment of the Cel-ind is at most moderate; echocardiography usually overestimates, but rarely underestimates, EA severity. Cel-ind by CMR seems to be more valuable, because it is associated with heart failure markers.

Hepcidin and Iron Homeostasis in Patients with Subacute Thyroiditis and Healthy Subjects.

PURPOSE: Hepcidin is an acute-phase protein involved also in regulation of iron homeostasis. The aim of the study was to prospectively assess for the first time the hepcidinEL concentration in patients with subacute thyroiditis (SAT), to identify biochemical determinants of hepcidinEL concentration and evaluate the potential role of hepcidin in SAT diagnosis and monitoring. METHODS: Out of 40 patients with SAT initially recruited, restrictive inclusion criteria fulfilled 21 subjects aged 45 ± 10 years and 21 healthy control subjects (CS). HepcidinEL concentration, thyroid status, and iron homeostasis were evaluated at SAT diagnosis and following therapy and compared with CS. RESULTS: The median hepcidinEL concentration at SAT diagnosis is higher than that in CS (48.8 (15.9-74.5) ng/mL vs. 18.2 (10.2-23.3) ng/mL, p = 0.009) and is significantly lower after treatment (4.0 (1.2-10.0) ng/mL, p = 0.007) compared with CS. The ROC analysis for hepcidinEL at SAT diagnosis revealed that area under the curve (AUC) is 0.735 (p = 0.009), and the cut-off for hepcidinEL concentration is 48.8 ng/mL (sensitivity 0.52 and specificity 0.95). HepcidinEL in SAT patients correlated with CRP (r = 0.614, p = 0.003), ferritin (r = 0.815, p < 0.001), and aTPO (r = -0.491, p = 0.024). On multiple regression, the correlation between hepcidinEL and ferritin was confirmed (p < 0.001). CONCLUSIONS: SAT is accompanied by a significant increase in hepcidin, which reflects an acute-phase inflammatory process. Parameters of iron homeostasis improved significantly while inflammatory indices got lower following recovery. The potential role of hepcidin as a predictive factor of the risk of SAT relapse needs to be assessed in studies on larger groups of SAT patients.

Clinical aspects of myocardial fibrosis in adults with Ebstein's anomaly.

Heart failure and arrhythmia are common complications in adults with Ebstein's anomaly. They may result not only from hemodynamic alterations, but also from myocardial fibrosis. Late gadolinium enhancement (LGE) by CMR enables the evaluation of myocardial fibrosis. The aim of the study was to asses the presence of LGE and its relation to clinical outcome. We studied a group of 37 unoperated adults aged 43.0 ± 14.4 years with Ebstein's anomaly from the congenital heart disease outpatient clinic. Study protocol included: cardiopulmonary test, assessment of supraventricular arrhythmia (SVA), and CMR with evaluation of cardiac chambers' morphology and function, and presence of LGE. Variables following normal distribution were shown as mean ± SD if otherwise median (range) was applied. Fibrosis was found in 18 patients (48.6%) and was distributed as follows: 12 patients (32.4%) in the right atrium, 12 (32.4%) in the atrialized right ventricle, and 2 (5.4%) in the functional right ventricle. In patients with fibrosis, the tricuspid regurgitation fraction was bigger (48.3 ± 19.7 vs. 36.1 ± 22.6%, p = 0.048) and SVA was more frequent [12 (66.7%) vs. 6 (31.6%), p = 0.046] when compared to patients without fibrosis. However, exercise capacity did not differ between patients with and without LGE (peak VO2 24.0 ± 4.7 vs. 23.7 ± 4.4, p = 0.87). In adults with Ebstein's anomaly fibrosis estimated by LGE-CMR was localized in the right atrium and the right ventricle only. Volume overload resulting from tricuspid regurgitation might be a factor conducive to fibrosis. Myocardial fibrosis did not influence exercise capacity. Association between myocardial fibrosis and supraventricular arrhythmia was confirmed.

CXCL10 and CXCL13 chemokines in patients with relapsing remitting and primary progressive multiple sclerosis.

OBJECTIVES: Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system characterized by a variable clinical course. Different pathogenic mechanisms responsible for relapsing remitting (RRMS) and primary progressive multiple sclerosis (PPMS) are modulated by immunological process with important role of chemokine network. CXCL10 and CXCL13 chemokines act as chemoattractants and modulators of proinflammatory reactions promoting process of demyelination. In the present study, we investigated the concentrations of CXCL10 and CXCL13 in serum and cerebrospinal fluid (CSF) of patients with RRMS and PPMS. MATERIALS AND METHODS: The study groups comprised 25 RRMS patients (39,5±12years), 24 PPMS patients (49,9±10,5years), 31 healthy individuals (36±10,4years) with tension headache without symptoms of inflammatory diseases. A quantitive test kit based on ELISA has been used for chemokines measurement. Correlations analysis between the levels of CXCL10, CXCL13 and patient age, duration of MS, EDSS and IgG index were done. RESULTS: The mean concentration of CXCL10 in the CSF was statistically significantly higher in RRMS in comparison with the control group. The mean concentration of CXCL13 in the CSF was significantly higher in RRMS and PPMS than in the control group. The results have shown that in the stable phase of MS without relapse, mean concentration of CXCL10 and CXCL13 in CSF did not differ significantly between RRMS and PPMS. In PPMS a positive correlation between IgG index and CSF CXCL10 level or CSF CXCL13 level was observed. In RRMS a positive correlation between IgG index and CSF CXCL13 level was observed. CONCLUSIONS: These data indicate involvement of CXCL10 and CXCL13 chemokines in immunopathogenetic mechanisms in MS. There was no significant difference between mean CXCL10 or CXCL13 concentrations in the CSF in both RRMS and PPMS patients. No significant correlations were found between patient age and chemokines levels in theCSF in all groups. It suggest that these chemokines play similar role in inflammatory process despite more pronounced neurodegenerative process in PPMS.

Percutaneous Trans-Coronary Venous Mitral Annuloplasty in Patients With Functional Mitral Regurgitation: Analysis of Poznan Carillon Registry Data.

OBJECTIVES: The purpose of our study is to verify, whether percutaneous mitral annuloplasty results in reverse remodeling in patients with functional mitral regurgitation (FMR) and impaired ejection fraction (EF) and to investigate which echo parameters may help in prediction of the efficacy of the procedure. BACKGROUND: FMR exacerbates left ventricular (LV) dilatation and contributes to both LV remodeling and heart failure. METHODS: We analyzed baseline and 1 month follow-up data in 22 consecutive patients with FMR, who underwent successful percutaneous trans-coronary venous mitral annuloplasty with the Carillon device. RESULTS: Significant reduction of FMR echo parameters, including vena contracta (VC), effective regurgitant orifice area (EROA), and regurgitant volume (RV) were observed and maintained throughout 1 month follow up and did not correlate with baseline annular, LV or with the left atrial diameters. Baseline mitral tenting area correlated negatively with the relative improvement (% difference) of EROA (r = -0.5898) and RV (r = -0.4363), but not with VC (r = 0.1341). In addition, increased EF as well as a significant reduction in left ventricular diameters were noted. The increase in EF negatively correlated with the change in EROA (r = -0.50058), PISA (r = -0.5327), and RV (r = -0.5457). Baseline mitral tenting area significantly correlated with the 1 month change in EF (r = 0.5946) and stroke volume (r = 0.6913). CONCLUSIONS: The improvement of FMR after treatment with the Carillon device is associated with LV reverse remodeling and an increase in systolic performance, that correlates with the reduction in mitral regurgitation, being not dependent on baseline heart diameters. Mitral tenting area seems to be an important parameter in prediction of benefit from percutaneous mitral annuloplasty.

Comparison of Baseline Heart Rate Variability in Stable Ischemic Heart Disease Patients with and without Stroke in Long-Term Observation.

GOAL: Decreased heart rate variability (HRV) has predictive value in postinfarction as well as in ischemic stroke patients. However, it is unknown if ischemic heart disease (IHD) patients who are at high risk of stroke have different HRV profile. The goal of this study was to compare baseline HRV (traditional and novel indices) in stable IHD patients with and without stroke in long-term observation. METHODS: A total of 139 consecutive patients with stable IHD scheduled for coronary angiography were enrolled. Five-minute electrocardiogram readings were taken. Traditional and novel HRV measures were calculated. After 70.06 ± 4.297 months of follow-up, baseline HRV indices in patients who had had a stroke were compared with indices in patients without the aforementioned cerebrovascular event. RESULTS: During follow-up, 6 patients developed stroke. Compared to patients without such a cerebrovascular event, these patients with stroke had lower values for the following HRV indices: de Hann long-term irregularity (30,521 ± 32,767 versus 46,678 ± 25,328; P < .05), Yeh interval index (.0207 ± .0208 versus .0326 ± .0157; P < .05), Organ BAND (3.0563 ± 3.328 versus 4.515 ± 2.276; P < .05), Dalton standard deviation (SD) (17,887 ± 17,636 versus 29,859 ± 16,478; P < .05), Zugaib short-term variability (.004 ± .00416 versus .00622 ± .00418; P < .05), Zugaib long-term variability (.0161 ± .0151 versus .0247 ± .0115; P < .05), standard deviation of all NN intervals (8,954 ± 8,812 versus 16,724 ± 11,594; P < .05), total power (2,616 ± 4,855 versus 4,678 ± 4,653; P < .05), w2 (.71 ± .338 versus 1.719 ± 1.08; P < .05), w3 (1.399 ± .924 versus 2.552 ± 1.609; P < .05), and w4 (1.367 ± 1.705 versus 2.824 ± 2.027; P < .05). No significant differences in other analyzed indices were observed. CONCLUSIONS: Patients with IHD and stroke in long-term observation have different baseline profiles of HRV indices. Further investigations are needed to assess the usefulness of HRV analysis in stroke risk assessment.

Microvolt T-wave alternans in adult patients with repaired tetralogy of Fallot.

OBJECTIVE: Indications for sudden cardiac death (SCD) primary prevention are unknown in patients with repaired tetralogy of Fallot (ToF). The role of microvolt T-wave alternans (MTWA) in SCD risk stratification was documented. However, the prevalence of spectral MTWA and its association with ventricular arrhythmia (VA) in adults after ToF repair were not elucidated. DESIGN: Microvolt T-wave alternans, electrocardiogram (ECG), ambulatory ECG monitoring, echocardiography, and spiroergometry were evaluated in 102 adults after ToF repair. Microvolt T-wave alternans results were classified as normal: negative(-), abnormal: positive(+), and indeterminate(ind). Owing to similar prognostic significance, MTWA(+) and MTWA(ind) due to patient factors were combined into nonnegative group: MTWA(abnormal). RESULTS: Microvolt T-wave alternans(abnormal) was more frequent in the studied group as compared with controls (P = .0005). The MTWA(abnormal) group had greater right ventricular end-diastolic diameter (P = .005), higher incidence of pulmonary regurgitation (P = .015), lower peak oxygen consumption (P = .01), and higher VE/VCO2 slope (P = .04) in comparison with MTWA(normal). Univariate logistic regression proved pulmonary regurgitation (OR = 3.57, 95% CI 1.27-10.04), VA (OR = 3.26, 95% CI 1.06-10.05), right ventricular end-diastolic enlargement (OR = 1.11, 95% CI 1.03-1.2), increase in VE/VCO2 slope (OR = 1.08, 95% CI 1.01-1.17), and decrease in peak oxygen uptake (OR = .91, 95% CI 0.83-0.99) to increase MTWA(abnormal) prevalence. CONCLUSIONS: In adults after ToF repair, abnormal MTWA occurred more often than in controls. Probability of abnormal MTWA did not rise with prevalence of malignant VA; however, presence of abnormal MTWA was associated with VA risk factors: pulmonary regurgitation, right ventricular enlargement, and consequent heart failure. The role of MTWA in selecting patients late after ToF repair at risk of SCD needs further observation.

Aerosolized albuterol sulfate delivery under neonatal ventilatory conditions: in vitro evaluation of a novel ventilator circuit patient interface connector.

BACKGROUND: Aerosolized medications that have been used in infants receiving ventilatory support have not been shown to be effective clinically among the smallest patients. The aim of this study was to characterize the delivery of aerosolized albuterol sulfate in vitro under simulated neonatal ventilatory conditions using a novel ventilator circuit/patient interface connector. METHODS: A Babylog(®) ventilator (VN500(®); Draeger), a novel ventilator circuit/patient interface (VC) connector (Afectair(®); Discovery Laboratories, Inc.), a TwinStar(®) HME (Draeger) low-volume filter, and either a test lung (Draeger) or lung simulator ASL 5000(®) (IngmarMed) were used. Intermittent mandatory ventilation conditions were set to replicate the most typical ventilation conditions for premature infants. Continuous positive airway pressure was also used to measure aerosol delivery with active respiratory drive from the patient. Albuterol sulfate (0.5 mg/mL) was loaded into the drug reservoir of a Misty Finity(®) nebulizer (Airlife(®); Cardinal Health) and connected to the ventilator circuit either via a "T" connector as described by the manufacturer [standard of care (SoC)] or via the VC connector. Albuterol extracted from the filters was analyzed using qualified high-performance liquid chromatography. In addition, a laser diffraction spectrometry (Spraytec(®); Malvern) and white-light spectrometry (Welas model 2100; Palas GmbH) were used to determine particle size distribution (PSD). RESULTS: Compared with SoC, the amount of albuterol delivered using the VC connector was significantly greater (p<0.001) under simulated neonatal ventilatory conditions. Additionally, the PSD profile of albuterol sulfate delivered using the VC connector was more representative of the PSD profile directly from the nebulizer. CONCLUSIONS: The use of the VC connector increased the delivery of albuterol sulfate and resulted in a PSD profile at the patient interface that is more consistent with the PSD profile of the selected nebulizer when compared with SoC. This VC connector may be a useful, new approach for the delivery of aerosolized medications to neonates requiring positive pressure ventilatory support.

Microvolt T-wave alternans in adults with complex congenital heart diseases.

BACKGROUND: Sudden cardiac death (SCD) mostly resulting from ventricular arrhythmia remains a cause of mortality in 19-30% of adults with congenital heart defects. Indications for implantable cardioverter-defibrillators in primary prophylaxis are still under research. MicrovoltT wave alternans (MTWA) is one of the SCD risk stratification methods. We determined the incidence of MTWA in these patients and its coincidence with ventricular arrhythmia, as well as risk factors of ventricular arrhythmia/SCD. METHODS: 204 patients with complex congenital heart anomalies and 45 healthy volunteers underwent ambulatory ECG monitoring, a cardiopulmonary test, B-type natriuretic peptide assessment, echocardiography and an MTWA test. After excluding technically inadequate traces, the remaining 179 patients and 43 controls were classified into MTWA positive (+), negative (-) and indeterminate (ind) subgroups. Additionally, MTWA (+) and MTWA (ind) formed an 'abnormal' group, labeled MTWA (non-). RESULTS: Abnormal MTWA was observed more frequently in the study group compared to controls (59 [33.0%] vs. 1 [2.3%], p = 0.000001). The MTWA (non-) group compared to MTWA (-) presented a higher number of males (61.0% vs. 37.5%, p = 0.005), predominance of patients with NYHA > I (44.1% vs. 25.0%, p = 0.007), pulmonary hypertension (16.9% vs. 0.8%, p = 0.00007), lower blood saturation (97% [73-100] vs. 99% [69-100], p = 0.0003), higher incidence of malignant arrhythmia (9 [15.2%] vs. 3 [2.5%], p = 0.003), lower peak oxygen consumption VO2 [mL/kg/min] (23.1 ± 5.9 vs. 26.3 ± 6.7, p = 0.002), higher VE//VCO2 slope (36.0 [25-74] vs. 31.0 [21-58], p = 0.01). Multivariate logistic regression analysis proved that pulmonary hypertension (OR = 13.7, p = 0.03), male gender (OR = 10.4,p = 0.00002), VE/VCO2 slope (OR = 1.07, p = 0.045) and VO2 (OR = 0.89, p = 0.04) increase the probability of MTWA (non-). CONCLUSIONS: Abnormal MTWA is more frequent in adults with congenital heart diseases than in the healthy population. Its probability increases in patients demonstrating clinical findings conducive to lethal arrhythmia like heart failure and pulmonary hypertension.

Microvolt T wave alternans in adults with congenital heart diseases characterized by right ventricle pathology or single ventricle physiology: a case control study.

BACKGROUND: Among adults with congenital heart diseases (CHD) evaluation of sudden cardiac death (SCD) risk remains a great challenge. Although microvolt T-wave alternans has been incorporated into SCD risk stratification algorithm, its role in adults with CHD still requires investigation. We sought to determine the incidence of MTWA in this specific group and its coincidence with ventricular arrhythmia (VA) and other clinical findings presumably associated with SCD. METHODS: A case-control study was performed in which 102 patients with CHD characterized by right ventricle pathology or single ventricle physiology (TGA, UVH, Ebstein's anomaly, ccTGA, Eisenmenger syndrome, DORV, CAT, unoperated ToF) were compared to 45 age- and sex-matched controls. All subjects underwent spectral MTWA test, ambulatory ecg monitoring, cardiopulmonary test, BNP assessment. After excluding technically inadequate traces, the remaining MTWA results were classified as positive(+), negative(-) and indeterminate(ind). Due to similar prognostic significance MTWA(+) and (ind) were combined into a common group labeled 'abnormal'. RESULTS: Abnormal MTWA was present more often in the study group, compared to controls (39.2% vs 2.3%, p = 0.00001). Sustained ventricular tachycardia (sVT) was observed more often among subjects with abnormal MTWA compared to MTWA(-): 19.4% vs 3.6%, p = 0.026. The patients with abnormal MTWA had a lower blood saturation (p = 0.047), more often were males (p = 0.031), had higher NYHA class (p = 0.04), worse cardiopulmonary parameters: %PeakVO2 (p = 0.034), %HRmax (p = 0.003). Factors proven to increase probability of abnormal MTWA on multivariate linear regression analysis were: sVT (OR = 20.7, p = 0.037) and male gender (OR = 15.9, p = 0.001); on univariate analysis: male gender (OR = 2.7, p = 0.021), presence of VA (OR = 2.6, p = 0.049), NYHA > I (OR = 2.06, p = 0.033), %HRmax (OR = 0.94, p = 0.005), %PeakVO2 (OR = 0.97, p = 0.042), VE/VCO2slope (OR = 1.05, p = 0.037). CONCLUSIONS: Abnormal MTWA occurs significantly more often in adults with the chosen forms of CHD than among healthy subjects. The probability of abnormal MTWA increases in patients with malignant VA, in males and among subjects with heart failure and cyanosis. MTWA might be of potential role in risk stratification for SCD in adults with CHD.

[Selected biochemical parameters of oxidative stress as a result of exposure to tobacco smoke in animals addicted to ethyl alcohol]. / Wybrane parametry biochemiczne stresu oksydacyjnego w wyniku ekspozycji na dym tytoniowy zwierzat uzaleznionych od alkoholu etylowego.

Smoking cigarettes and alcohol addiction are serious problems in health hazard and life of society. Tobacco smoke leads to many kinds of cancer formation and scientific research indicates, that heart-vascular disease and lung cancer are the most common diseases caused by tobacco smoke. While talking about ethanol, it is responsible for liver, pancreas, mucous membrane damage and leads to central and circular nervous disorder. Scientific research indicates, that many smokers drink alcohol and vice versa. Unfortunately in that case the risk of many diseases increases. Both of these stimulants leads to enlarged production of reactive oxygen species, which is connected with unbalance between pro and antioxidant processes in human organism. Free radicals in normal conditions plays positive role but with tobacco smoke and alcohol connection may lead to serious changes in human organism. They damage organs, it comes to protein structure, nucleic acid and fat violation, which in consequence leads to immunity decrease and many pathological changes. Reactive oxygen species also plays role in pathogenesis of many diseases: diabetes mellitus, atherosclerosis and Down syndrome. ROS may also increase the risk of pancreas, lung, larynx and urinary bladder cancer formation. Human organism defends oneself from harmful influence of reactive oxygen species owing to enzymatic and non-enzymatic systems presence-Non-enzymatic antioxidants: glutathione, carotene, bilirubin, tocopherol, uric acid and ions metals temporary complex belong to non-enzymatic systems. To enzymatic ones belong: catalase, superoxide dismutase, glutathione reductase and glutathione peroxidase. The aim of the study was tobacco smoke and ethyl alcohol influence evaluation in rats addicted to these substances on activity of chosen enzymes responsible for organism defense against toxic compounds action. To this study 63 white, Wistar tribe rats at the age of 3,5 months were used - males addicted to ethyl alcohol. They were divided into 3 groups, each consist of 21 rats. Animals of Group I were exposed on harmful tobacco smoke influence. Group II constitute animals, which were given by stomach probe 10% alcohol dilution once at a dose of 2 g/kg weight. The next Group - III, in which animals at first were exposed on tobacco smoke influence. When exposition was over, animals were given by stomach probe 10% alcohol dilution once at a dose of 2 g/kg weight. Depending on the type of marker and studied organ, changes in the levels of selected enzymes, responsible for defending organism against reactive forms of oxygen has been shown. Both tobacco smoke and ethyl alcohol resulted in a change of glutathione levels in the serum and tissues of animals. Tobacco smoke has the biggest influence on protein nitrozylation in the brain and ethyl alcohol had influence on glutathione level in serum, kidney, brain and superoxide dismutase activity in the brain. Application of many oxidative stress markers allows for evaluation of its differential influence on various organs.

Augmentation of central arterial pressure in adult patients after coarctation repair.

OBJECTIVES: Arterial hypertension and its complications are associated with an increased morbidity and mortality in patients after aortic coarctation (CoA) repair. It is debatable whether early surgery can prevent it. Residual stenosis of descending aorta (AoD) and stiffness in the precoarctation region supposedly lead to hypertension. The aim of this study was to evaluate aortic pulse-wave parameters in adult patients after CoA repair and to determine the influence of residual stenosis and age at operation on their values. METHODS: Eighty-five patients underwent CoA repair (53 males; aged 34.6±10.3 years, age at operation: 10.9±8.2 years). The control group consisted of 30 individuals (18 males; aged 33.6±8.2 years). Augmentation pressure (AP), augmentation index (AI), aortic pulse pressure (APP), and pulse-wave velocity (PWV) were measured with applanation tonometry method. RESULTS: Normotensive patients after CoA repair (47/55%) had higher values of AP (7.3±4.6 vs. 4.4±3.6 mmHg; P=0.002), AI (18.6±10.4 vs. 13.5±4.3%; P=0.03), APP (39.6±8.8 vs. 35.1±9.8; P=0.00001), and PWV (6.8±1.2 vs. 5.4±0.9 m/s; P=0.003) than controls. Forty-six patients presented signs of recoarctation. No significant differences in the systolic blood pressure and diastolic blood pressure, AI and PWV were found between AoD(+) and AoD(-) but AoD(+) had significantly higher APP (46.7±13.8 vs. 38.3±6.9; P=0.001) and AP (10.5±6.9 vs. 7.5±4.1; P=0.02). Significant correlations were found between current age and APP, AP, and AI. No significant correlations were found between central parameters and the age at operation. CONCLUSION: Normotensive patients after CoA repair have elevated central parameters, related to the residual AoD gradient, regardless of the age at operation. Even early repair cannot prevent progressive vascular impairment in CoA.

[Analysis of the odds ratio for developing breast cancer in women]. / Analiza ilorazu szans zachorowania na nowotwory zlosliwe gruczolu piersiowego kobiet.

Malignant breast cancer is the most common neoplasm in women in most developed countries. The majority of cases of breast cancer are probably connected with environmental factors and lifestyle. According to the current state of knowledge, modification of risk factors may contribute to the reduction of breast cancer cases and individual assessment performed by selecting a group of women with increased risk may help to reduce mortality. The purpose of the study was to analyze risk factors affecting the increase of odds ratio (OR) for developing breast cancer and to define in which range OR increases or decreases significantly. The participants of the study were healthy women with no changes in mammary glands and women with breast cancer diagnosed on the basis of histopathological examination. The study was carried out in Great Poland and Lubuskie province between 2005 and 2006. The total number of participants was 371 females, aged 35-70 years. The highest risk of breast cancer was observed in women over 55, BMI > 30, who had > 5 deliveries, with cancer family history and suffering from severe depression. Apart from cancer family history all other factors are potentially modifiable. Appropriate education of women can result in reduction of breast cancer risk.

Vascular remodeling in adults after coarctation repair: impact of descending aorta stenosis and age at surgery.

BACKGROUND: Patients after successful repair of coarctation of aorta (CoAo) are at risk of hypertension at rest and associated end-organ damage. The aim of the study was to assess arterial stiffness and function in adults after coarctation repair in relation to descending aorta (AoD) residual coarctation and patient's age at operation. METHODS: 85 patients after CoAo repair (53 males) aged 34.6 ± 10.3 years; median age at operation 0.9 ± 8.2 years. The control group-30 individuals (18 males) at mean age 33.6 ± 8.2 years. The following central parameters: augmentation pressure (AP) and augmentation index (AI) as well as peripheral vascular parameters: flow-mediated dilatation (FMD), nitroglycerin-mediated vasodilatation (NMD), intima-media thickness (IMT) and pulse wave velocity (PWV) were measured. RESULTS: 47 CoAo-repaired patients were normotensive, and compared to control, they presented higher values of central parameters AP (7.3 ± 4.6 vs. 4.4 ± 3.6 mmHg; p = 0.002) and AI (18.6 ± 10.4 vs. 13.5 ± 4.3%; p = 0.03); as well as the increased PWV (6.8 ± 1.2 vs. 5.4 ± 0.9 m/s; p = 0.003), while IMT was comparable (0.53 ± 0.01 vs. 0.51 ± 0.01 mm; p = 0.06). The vasodilatation was impaired in the normotensive patients: FMD (4.8 ± 2.8 vs. 8.5 ± 2.3%; p = 0.00003) and NMD (11.3 ± 4.6 vs. 19.8 ± 7.2%; p = 0.00001). The comparison of recoarctation (46, 54%) to non-recoarctation (39, 46%) patients did not reveal any significant differences in resting systolic and diastolic pressures, as well as the values of AI and the peripheral vascular parameters; the value of AP was higher in the recoarctation patients (10.5 ± 6.9 vs. 7.5 ± 4.1; p = 0.02) and correlated positively with the gradient across AoD (r = 0.295, p = 0.01). There was no significant linear correlation between age at the time of surgery and any of peripheral arterial parameters. CONCLUSIONS: Residual stenosis in AoD does not affect the arterial vasodilatation nor stiffness in patients after CoAo repair. Early operation has no impact on peripheral vascular remodeling or central pressure which supports the claim that coarctation of the aorta is a systemic vascular disorder which leads to progressive vascular and end-organ damage despite early correction.

Parameters of arterial function and structure in adult patients after coarctation repair.

Regardless of a successful operation, patients with coarctation of aorta (CoAo) are exposed to the risk of hypertension and a propensity to vascular and end-organ damage. The aim of this study is to evaluate the influence of residual aorta stenosis as well as the age at the operation on the parameters of arterial function and structure in patients after CoAo repair. Eighty-five patients after CoAo repair (53 males; mean age: 34.6 ± 10.3 years, mean age at the repair: 10.9 ± 8.2 years) were enrolled in the study. The control group consisted of 30 healthy subjects (18 males; mean age: 33.6 ± 8.2 years). Indices of systemic arterial remodeling [flow-mediated dilatation (FMD), nitroglycerine-mediated vasodilatation (NMD), carotid intima-media thickness (IMT), pulse wave velocity (PWV)] were analyzed in all study patients. In normotensive patients after CoAo repair (47/55%), a significantly increased PWV was observed in comparison to the control group (6.8 ± 1.2 vs. 5.4 ± 0.9 m/s; p = 0.003), with no difference in IMT values (0.53 ± 0.1 vs. 0.51 ± 0.1 mm; p = 0.06). Mean FMD (4.8 ± 2.8 vs. 8.5 ± 2.3%; p = 0.00003) and NMD (11.3 ± 4.6 vs. 19.8 ± 7.2%; p = 0.00001) were lower than in the controls. In patients with a residual aorta stenosis (46/54%), defined as an arm-leg pressure gradient ≥ 20 mmHg, no differences were found within the scope of both systolic and diastolic blood pressure and of all of the examined vascular parameters. No significant correlations were revealed between the vascular parameters and the gradient across descending aorta as well as the age at the operation. Residual stenosis in the descending aorta does not affect the arterial vasodilatation nor stiffness in patients after CoAo repair. An early surgery does not influence the remodeling of the vessels, which supports the thesis that CoAo is a generalized vascular disease and that even an early operation cannot prevent the progressive and vascular changes and end-organ damage.

Carbamazepine intoxication in alcohol dependent epileptic patients.

Carbamazepine is frequently administrated to alcohol addict patients. The aim of this study was to evaluate the influence of alcohol addiction on carbamazepine pharmacokinetics and severity of drug intoxication. The total of 158 carbamazepine intoxicated patients participated in the study (76 non-alcohol-dependent, and 82 alcohol-dependent subjects). The results of the study indicate that the level of unconsciousness depends on carbamazepine concentration. The frequency of anticholinergic toxidrome was higher in alcohol-dependent patients (88.6% - alcohol-abused subjects, and 78.3% - alcoholics in abstinency) comparing to non-alcohol-dependent epileptics (67.1%). The average biological half-life of carbamazepine in non-addicted epileptics was 41.5 h, 43.5 h for alcohol-dependent patients during abstinency, and 38.6 in abused patients. It may be concluded that ethanol doesn't influence the pharmacokinetic and pharmacodynamic of carbamazepine in acute drug intoxication.

Predictors of mortality in adult patients with congenital heart disease.

BACKGROUND: Most patients with congenital heart disease (CHD) reach adulthood thanks to the successful efforts of cardiac surgeons. However, sudden cardiac deaths are significantly more prevalent in this population, and survival is reduced when compared to the general population. The aim of this study is to define the prognostic value of selected clinical parameters to predict mortality in adult CHD patients referred to the specialist outpatient centre. The following parameters were analyzed as potential predictors of long-term survival: complexity of heart defect, past surgical intervention, heart failure (functional class according to NYHA > I), cyanosis, age and gender. METHODS: We analyzed data gathered from 1,304 patients (568 male) aged 18 to 72 (mean 29.4 +/- 10.6) between 1995 and 2004. Mean duration of follow-up was 3.52 +/- 1.83 years. RESULTS: During follow-up, 29 deaths were recorded (2.2%). Higher mortality was found in the group of patients with complex as oppposed to simple CHD (28 [6.7%] vs. 1 [0.1%]; p = 0.00001), in subjects without surgical correction as opposed to those operated on (21 [6.1%] vs. 8 [0.8%], p = 0.00001). General survival was 99.1% at two years and 96.6% at five years. In univariate survival analysis, all single clinical variables except patient gender were associated with increased risk of death (p = 0.00001 for all). All patients who died presented with heart failure. In multivariate analysis, the independent predictor of mortality was cyanosis (heart rate 38.1). Complexity of lesion (heart rate 6.4) represented a relative risk factor. CONCLUSIONS: Heart failure and cyanosis are negative predictors of survival in adult patients with CHD. Complexity of the lesion increases the relative risk of mortality. Past cardiac surgery is associated with better survival, but, as with age and gender, it is not a significant prognostic factor.

Risk factors of supraventricular arrhythmia in adults with congenital heart disease.

BACKGROUND: Supraventricular arrhythmia (SVA) is a frequent clinical complication in adult patients with congenital heart disease (CHD). The aim of this study is prognostic evaluation of congenital heart defect complexity, performed cardiac surgery, initial functional impairment of the heart - NYHA > I, cyanosis, age and sex of the adult patients with CHD, presenting for the first time to an outpatient clinic, on SVA occurrence during long-term observation. METHODS: We looked at 1,304 patients (586 men), aged 18-72 years (mean 29.4 +/- 10.6 years), and followed-up from 1995 to 2004. The mean observation period was 3.52 +/- 1.83 years. SVA in the form of atrial flutter/fibrillation (FA/FLA) and supraventricular tachycardia was observed in 133 patients, 10.3% of the study population. Ten-year follow-up showed that the likelihood of SVA occurrence in the whole studied population after two years was 5.2%, and 14.4% after ten years. RESULTS: Univariate analysis proved that the incidence of SVA is greater in patients with complex heart defects (p = 0.0001), those not previously operated upon (p = 0.0001), those with baseline impairment of cardiac function (NYHA > I; p = 0.0001) and those with cyanosis (0.0001). The patient's sex seems to have little significance. Cox regression analysis showed that baseline heart failure is the strongest risk factor for SVA (HR = 4.66). Congenital heart defect complexity (HR = 2.31) and the patient's age are also significant prognostic factors of this arrhythmia (HR = 1.32). Cardiac surgery, cyanosis and patient sex are not significant in prognosis. CONCLUSIONS: Baseline impairment of heart function, heart defect complexity and patient's age all increase the risk of SVA in the population of adults with congenital heart disease. Cyanosis and the lack of cardiac surgery in the past led to a higher incidence of the analyzed arrhythmia but are not risk factors for its occurrence. Gender has no prognostic significance for SVA.