Risk Factors for Normal and High-Tension Glaucoma in Poland in Connection with Polymorphisms of the Endothelial Nitric Oxide Synthase Gene.

AIM: The purpose of this study was to evaluate the influence of polymorphisms of the eNOS gene on the clinical status of patients with normal and high tension glaucoma. METHODS: 266 Polish Caucasian patients with primary open angle glaucoma were studied. Of the 266, 156 had normal tension glaucoma (NTG) and 110 high tension glaucoma (HTG). DNA material was isolated from peripheral venous blood using commercial kits. Real-time PCR reaction was used to amplify the promoter site of the endothelial nitric oxide synthase (eNOS) gene, including the single nucleotide polymorphism (SNP) site T-786C and part of the 7th exon of eNOS, including G894T SNP. Genotypes were determined with TaqMan SNP Genotyping Assays. RESULTS: There were no significant differences in frequencies of the allelic variants of both polymorphisms. In G894T SNP, however, the wild GG form was more common in the HTG group. The SNP of the eNOS gene did not significantly influence the progression rate in either of the groups studied. There were no differences in variants of the eNOS gene regarding the necessity for and success of surgery and the progression of the disease. In the NTG group, no statistical correlation was observed between G894T, T786C polymorphism variants, and risk factors such as optic disc haemorrhages, optic disc notches, and peripapillary atrophy. Mean diastolic and systolic pressure during the day and night were lowest in NTG patients with the CC variant of the T786C polymorphism. No statistical correlation was observed between the G894T and T786C polymorphisms and capillaroscopic examination results. CONCLUSIONS: Genotype frequencies are similar for both the eNOS G894T and T-786C polymorphisms in NTG and HTG patients. These polymorphisms do not correlate with risk factors and do not influence the state of the capillary system in NTG patients. Systolic blood pressure is lower in NTG patients with mutated alleles of both polymorphisms.

Risk Factors in Normal-Tension Glaucoma and High-Tension Glaucoma in relation to Polymorphisms of Endothelin-1 Gene and Endothelin-1 Receptor Type A Gene.

The aim of the research is to analyse the influence of polymorphisms of endothelin-1 gene and endothelin-1 receptor type A gene on the clinical condition of patients with primary open angle glaucoma. Methods. 285 Polish patients took part in the research (160 normal-tension glaucoma and 125 high-tension glaucoma). DNA was isolated by standard methods and genotype distributions of four polymorphisms in genes encoding endothelin-1 (K198N) and endothelin-1 receptor type A polymorphisms (C1222T, C70G, and G231A) were determined. Genotype distributions were compared between NTG and HTG groups. The clinical condition of participants was examined for association with polymorphisms. Results. A similar frequency of occurrence of the polymorphic varieties of the studied genes was observed in patients with NTG and HTG. There is no relation between NTG risk factors and examined polymorphisms. NTG patients with TT genotype of K198N polymorphism presented with the lowest intraocular pressure in comparison to GG + GT genotype (p = 0.03). In NTG patients with CC genotype of C1222T polymorphism (p = 0.028) and GG of C70G polymorphism (p = 0.03) the lowest values of mean blood pressure were observed. Conclusions. The studied polymorphic varieties (K198N, C1222T) do have an influence on intraocular pressure as well as arterial blood pressure in NTG patients.

[Ventilatory disorders in patients with chronic heart failure]. / Zaburzenia czynnosci wentylacyjnej pluc u pacjentów z przewlekla niewydolnoscia serca.

Chronic heart failure (CHF) is a condition in which both structure and functional capacity of cardiac muscle are impaired, resulting in ineffective peripheral tissue perfusion. Affecting numerous organs and systems, it is currently considered to be a systemic illness. Among significant, however until now, hardly recognized consequences of CHF there are ventilatory disorders. Their presence may be explained by proximity of heart and lungs inside rib cage or by close functional cooperation between these two organs. Ventilatory disorders clinically manifest as exacerbations of the underlying disease, i.e. intense dyspnea--primarily exertional in nature, over time, present even at rest. On the basis of functional pulmonary tests, ventilatory disorders may be classified into three categories: restrictive, obstructive and most commonly--mixed. The restrictive model is represented in bodypletysmography as reduction in the total lung capacity to values less than 5th percentile of the predicted values for normals, while Tiffeneau index remains intact. Such condition may probably result from the chronic inflammatory process affecting lung tissue, for which the reaction of macrophage cells to both pulmonary stasis, as well as increased volume of interstitial and alveolar fluid remains the underlying cause. The increased formation of connective tissue fibers engenders thickening of alveolar-capillary membrane, occurrence of disturbed oxygen diffusion and emergence of hypoxemic respiratory failure. Ventilatory disorders of obstructive nature are characterised by reduction of Tiffeneau index--the calculated ratio between forced expiratory volume in 1. second and forced vital capacity--to values below 5th percentile of the predicted range. The research results indicate for the presence of bronchiolar narrowing--dominant in small-diameter bronchi and bronchioles, with larger structures being unaffected--clearly depicted in spirometry as reduced levels of forced expiratory flow after exhaling 50% and 75% of forced vital capacity. Due to a considerable epidemiological problem, as well as significance of the clinical symptoms manifesting ventilatory disorders in course of chronic heart failure, there should be put emphasis on cardiac injury prevention in individuals from risk groups and the proper treatment of patients already suffering from chronic heart failure.

[The involvement of galectin-3 in heart failure]. / Rola galektyny-3 w niewydolnosci serca.

Hart failure (HF) accounts for numerous serious problems: medical, social and financial. HF affects 2-3% adult population and its frequency increases with age. Despite advances in laboratory diagnostics of HR the use of biochemical markers remains limited. Currently, only natriuretic peptides, especially type B natriuretic peptides (BNP) and N-terminal fragment of pro-BNP (NT-proBNP) have been fully approved biomarkers employed in diagnosing HF. The concentration of those peptides fluctuates and largely depends on age, gender, renal function, day/night rhythm and volemia which reflects hemodynamic state rather than hart abnormal structure. As the application of natriuretic peptides is limited in certain groups of patients, it is necessary to search for other more stable biomarkers. Recent investigations have suggested galectin-3 (gal-3) to be a new promising cardiological marker. Gal-3 belongs to a family of lectins that demonstrate binding specificity for ß-galactoside which are produced by activated macrophages. Its operative path involves stimulation of cardiac fibroblasts and collagen production which can result in pathological remodeling of the myocardium structure. Numerous research found substantially increased gal-3 level in patients with chronic HF disregarding the etiology of disease. Moreover, some clinical studies have proved that increased gal-3 concentration is a factor of poor prognosis and predicative of death due to any reason in patients with HF. Contrary to natriuretic peptides, gal-3 is hemodynamically stable which is an additional asset of gal-3 as a marker of myocardial fibrosis.The article presents current state of research into gal-3 involvement in HF pathogenesis and possible use of gal-3 as a diagnostic marker of HF.

Acute respiratory distress syndrome (ARDS) in the course of influenza A/H1N1v infection--genetic aspects.

Influenza is a contagious respiratory disease caused by viruses belonging to the family Ortomyxoviridae. Among the influenza viruses type A, B and C, the A type virus shows the most pathogenic potential. Its surface receptor glycoproteins, hemagglutinin (HA) and neuraminidase (NA), are characterized by high antigenic variation, thus a host organism cannot develop permanent resistance. The case is described of a male patient with severe acute respiratory distress syndrome in the course of influenza A/N1H1v infection, confirmed by virological molecular analysis. During diagnostic procedures based on the MSSCP genotyping it was observed that the WHO recommended RT-PCR kits and/or procedure of sample collection from patients for molecular investigation could lead to false positive A/H1N1 pandemic strain detection because of the co-amplification during the RT-PCR fragments of the human genome.

Acute respiratory distress syndrome (ARDS) complicating influenza A/H1N1v infection--a clinical approach.

ARDS is defined as an acute inflammatory syndrome characterized with bilateral parenchymal lung infiltrates on chest radiograph and PaO2/FiO2 ratio<200 resulting from causes other than acute left ventricular dysfunction. Inflammatory lung lesions may be induced by different disorders, with sepsis being the leading cause of ARDS. Other causes include infectious pneumonia, aspiration of gastric contents, drugs, severe trauma, fat embolism, surface burn, massive blood transfusion. Influenza A/H1N1 infection seems to be responsible for the development of extremely severe type of ARDS with poor response to routine treatment. Despite great progress in the management of ARDS with novel agents and sophisticated techniques, including antimicrobial drugs, extracorporeal membrane oxygenation, prostaglandins, nitric oxide, prostacyclin, exogenous surfactant administration and activated protein C, supportive treatment based mostly on advanced mechanical ventilation in the intensive care units seems to be the most important for the prognosis.

Circadian rhythm of spectral indices of heart rate variability in healthy subjects.

Circadian pattern of heart rate variability spectral indices, including hourly, 24-hour, night, day, morning, and sex-adjusted measures of low frequency (LF), high frequency (HF), and LF/HF, was evaluated in healthy persons in 24-hour 3-lead electrocardiogram. HF showed circadian pattern with the greatest night values and LF/HF with the smallest night values. Peaks of hourly LF were found between 5 and 9 am and between 4 and 6 pm. The smallest LF was between 11 pm and 3 am. Hourly HF peaked between 11 pm and 5 am. The smallest HF was observed between midday and 2 pm. LF/HF peaked between 6 and 9 am as well as between 4 and 6 pm with the smallest values between midnight and 5 am. Sex adjustment was of no significance. In healthy subjects, HF and LF/HF have circadian pattern. Evaluation of all 5-minute intervals of 24-hour period seems to be a precise method of heart rate variability analysis.

Circadian rhythm of the QT interval dispersion in healthy subjects. Correlation with heart rate variability circadian pattern.

Circadian variation of QT interval dispersion (QTd) and heart rate variability spectral indices was evaluated in healthy persons in 24-hour 3-lead electrocardiogram. Mean values, SD, and SD/mean were evaluated for 24 hours, each hour separately and in night, day, and morning periods. Table Curve 2D and multiple regression were applied to find correlations between parameters. In 50% of subjects, a significant negative correlation was revealed between QTd and HF. Also, in 50% of persons, a significant positive correlation was found between QTd and low frequency/high frequency. After adjustment for periods, correlations were only observed during morning hours. With Table Curve 2D, 2 models of correlations between QTd and HF were found. Multiple regression analysis revealed relations between mean QTd and R-R as well as mean QTd and HF. It is possible that it is sympathovagal balance, as reflected in heart rate variability, and not the tone of both autonomic components that affects QTd variability.

Dihydrotestosterone treatment in men with coronary artery disease. II. Influence on myocardial ischemia and left ventricle.

The effect of transdermal dihydrotestosterone on left ventricle mass and its systolic and diastolic function as well as on the results of treadmill stress test was assessed in eleven males with coronary artery disease. DHT treatment for 3 months resulted in significant decrease in isovolumetric relaxation time (0.150+/-0.37 s vs. 0.135+/-0.03 s; p < 0.05) indicating the improvement of left ventricle diastolic function. Left ventricle mass and systolic function indices remained unchanged. There was improvement in myocardial ischemia, time to 1 mm ST segment depression increased (p < 0.05) and ST/HR slope decreased (p < 0.01). Correlation coefficients between testosterone concentration at the beginning of the study and differences in selected parameters of ECG stress test were as follows: for T and increased total exercise time (r= -0.83, p=0.002), for T and increased maximum workload (r= -0.84, p=0.001), for T and increased time to 1 mm ST segment depression (r= -0.75, p=0.009) and for T and decreased ST/HR slope (r=0.68, p=0.02).