Association of tumor necrosis factor and human leukocyte antigen DRB1 alleles with Graves' ophthalmopathy

Tumor necrosis factor (TNF)-alpha plays a central role in the development of ophthalmopathy in patients with Graves' disease (GD). The aim of this study was to investigate the association of TNF promoter polymorphisms at positions -1031 (T-1031C), -863 (C-863A), -857 (C-857T), -308 (G-308A), and -238 (G-238A) with Graves' ophthalmopathy (GO). We studied the distribution of TNF and human leukocyte antigen (HLA) DRB1 alleles in 228 Polish white patients with GD, 106 of whom had ophthalmopathy (NOSPECS class > or = III) and 248 healthy subjects. TNF -308A and HLA-DRB1*03 alleles were significantly increased in patients with GD compared with healthy subjects. Stratification analysis revealed no independent association of -308A with GD when the DRB1*03 status was considered. Subdividing GD according to eye involvement revealed that the distribution of TNF promoter haplotypes differed significantly in patients with or without ophthalmopathy. The haplotype containing the -238A allele was absent in GO. The association of G-238A with GO was independent of DRB1 alleles. These results indicate that TNF G-308A is associated with susceptibility to GD (however, this association is not independent of HLA-DRB1*03) and that TNF G-238A is associated with the development of ophthalmopathy, suggesting that G-238A or a gene in linkage disequilibrium may be disease modifying in GD.     

PTCA and left ventricular systolic function (evaluation by exercise two-dimensional echocardiography)]

Successful transluminal coronary angioplasty (PTCA) should improve left ventricular systolic function. To assess the effect of this procedure 25 patients with coronary heart disease were examined before and 3-to 5 days after successful PTCA with electrocardiographic treadmill exercise test, and exercise two-dimensional echocardiography (modified Bruce protocol). Echocardiographic examination was obtained prior to and immediately following exercise. Left ventricular ejection fraction and segmental wall motion at the baseline and immediately after exercise were assessed. Electrocardiographic evidence of ischemia was found in 16 of 25 patients prior to PTCA and in 9 patients after PTCA. Following angioplasty, exercise duration was increased and the exercise-induced angina rate was significantly decreased. Ejection fraction did not change significantly in patients prior and after PTCA (52 +/- 10% versus 55 +/- 16%, p = NS). Following angioplasty, ejection fraction increased from 55 +/- 10% (rest) to 64 +/- 11% (exercise) (p less than 0.001). New exercise-induced echocardiographic segmental wall motion abnormalities were found in 16 of 25 patients prior to PTCA and in only one patient following PTCA. Significant improvement of ejection fraction and segmental wall motion were also observed in 11 patients with old myocardial infarction subjected to successful angioplasty of infarct-related coronary artery. Opposite to post-exercise results, the resting mean values of these echocardiographic parameters did not differ significantly between pre and post-PTCA examinations. These data demonstrate an improvement in systolic left ventricular function and better exercise tolerance following successful PTCA. This occurs also in patients with old myocardial infarction after angioplasty of infarct-related coronary artery. Two-dimensional exercise echocardiography may be helpful in assessing the early results of successful angioplasty.     

Variants in the ATM‐CHEK2‐BRCA1 axis determine genetic predisposition and clinical presentation of papillary thyroid carcinoma

The risk of developing papillary thyroid carcinoma (PTC), the most frequent form of thyroid malignancy, is elevated up to 8.6‐fold in first‐degree relatives of PTC patients. The familial risk could be explained by high‐penetrance mutations in yet unidentified genes, or polygenic action of low‐penetrance alleles. Since the DNA‐damaging exposure to ionizing radiation is a known risk factor for thyroid cancer, polymorphisms in DNA repair genes are likely to affect this risk. In a search for low‐penetrance susceptibility alleles we employed Sequenom technology to genotype deleterious polymorphisms in ATM, CHEK2, and BRCA1 in 1,781 PTC patients and 2,081 healthy controls. As a result of the study, we identified CHEK2 rs17879961 (OR = 2.2, P = 2.37e‐10) and BRCA1 rs16941 (odds ratio [OR] = 1.16, P = 0.005) as risk alleles for PTC. The ATM rs1801516 variant modifies the risk associated with the BRCA1 variant by 0.78 (P = 0.02). Both the ATM and BRCA1 variants modify the impact of male gender on clinical variables: T status (P = 0.007), N status (P = 0.05), and stage (P = 0.035). Our findings implicate an important role of variants in the ATM‐ CHEK2‐ BRCA1 axis in modification of the genetic predisposition to PTC and its clinical manifestations. © 2014 Wiley Periodicals, Inc.     

Impact of Left Ventricular Remodeling on Ventricular Repolarization and Heart Rate Variability in Patients after Myocardial Infarction Treated with Primary PCI: Prospective 6 Months Follow‐up

Background: The relation between postinfarction left ventricle remodeling (LVR), autonomic nervous system and repolarization process is unclear. Purpose of the study was to assess the influence of LVR on the early (QTpeak) and late (TpeakTend) repolarization periods in patients after myocardial infarction (MI) treated with primary PCI. The day‐to‐night differences of repolarization parameters and the relation between QT and heart rate variability (HRV) indices, as well left ventricle function were also assessed. Methods: The study cohort of 104 pts was examined 6 months after acute MI. HRV and QT indices (corrected to the heart rate) were obtained from the entire 24‐hour Holter recording, daytime and nighttime periods. Results: LVR was found in 33 patients (31.7%). The study groups (LVR+ vs LVR?) did not differ in age, the extent of coronary artery lesions and treatment. Left ventricle ejection fraction (LVEF) was lower (38%± 11% vs 55%± 11%, P < 0.001), both QTc (443 ± 26 ms vs 420 ± 20 ms, P < 0.001) and TpeakTendc (98 ± 11 ms vs 84 ± 12 ms, P < 0.005) were longer in LVR + patients, with no differences for QTpeakc. Trends toward lower values of time‐domain (SDRR, rMSSD) HRV parameters were found in LVR+ pts. Day‐to‐night difference was observed only for SDRR, more marked in LVR‐group. Remarkable relations between delta LVEF (6 months minus baseline), delta LVEDV and TpeakTendc were found, with no such relationships for QTpeakc. Conclusions: The patients with LVR have longer repolarization time, especially the late phase‐ TpeakTend, which represents transmural dispersion of repolarization. Its prolongation seems to be related to local attributes of myocardium and global function of the left ventricle but unrelated to the autonomic nervous influences. Remodeling with moderate LV systolic dysfunction is associated with insignificant decrease in HRV indices and preserved circadian variability.     

Melatonin enhances antioxidant action of α‐tocopherol and ascorbate against NADPH‐ and iron‐dependent lipid peroxidation in human placental mitochondria

Abstract: Human placental mitochondria might be a significant source of NADPH‐ and iron‐dependent production of reactive oxygen species (ROS). Preeclampsia is believed to be a consequence of overproduction of ROS in human placenta. The experimental results presented here show that melatonin inhibits NADPH‐ and iron‐dependent lipid peroxidation of human placental mitochondria in a concentration‐dependent manner. At 1.5 mm concentration, melatonin suppressed this process nearly completely. Melatonin does not influence significantly the iron oxidation at this conditions, indicating that free radical scavenging rather than metal‐chelating phenomenon is the basis of its antioxidant action. The fact of inhibition of lipid peroxidation by melatonin at conditions excluding iron participation also supports this hypothesis. Elucidation of the nature of common interaction among melatonin, ascorbate, and α‐tocopherol in human placental mitochondria was the main aim of this study. In presence of 90 μm ascorbate, the inhibition of lipid peroxidation by melatonin was strong and had a feature of synergistic interaction. At presence of 30 μm ascorbate, which stimulated lipid peroxidation, melatonin caused a loss of pro‐oxidant effect of ascorbate. While the interaction of melatonin with ascorbate indicated synergism, the joint action of melatonin and α‐tocopherol was additive. When all three antioxidants were applied together, the strongest inhibition of lipid peroxidation was observed. The experimental results presented here indicated that melatonin could be considered as an effective component of antioxidant treatment of preeclampsia, allowing the use of reduced doses of vitamin C and E owing to elevated efficiency of their antioxidant activity in placenta when used in combination.     

Sociologic problems of contraception in the opinion of women from urban and rural areas

The paper, having a diagnostic character, discusses the problems of birth control, family planning and contraception methods. The methods of the investigation were a questionnaire, interview and analysis of documentation. The investigation was carried out in two areas: urban--Katowice and rural--Istebna. The investigation was carried out among a group of 100 women between 20 and 55 years of age. All the women questioned have been married for 1-30 years. Most of them have two children--30%. Most women from both the urban and rural areas use natural methods of contraception, in. the town--Billings method and in the country--conjugal diary. Thermal method is less popular as it is time-consuming. The main reasons for choosing a natural method of contraception control are moral, religious and biological aspects, which give the women a psychic comfort and a strong feeling of attachment to the husband. Women from the urban area say that they started to use contraceptive methods after getting married whereas women from the rural area--after giving birth to a child. Contraceptive devices are used by about 30% of women. The most popular are: among women from the town--coitus interruptus, artificial abortion and less popular contraceptive devices such as oral contraceptives, intrauterine devices and chemical substances. Among women from the rural area the most common is coitus interruptus and then 2-1 cases of each of the remaining methods. Women applying contraceptive devices are aware of their harmful effects, their unreliability, immorality and violating nature. Women in the country face a lot of difficulties in buying contraceptive devices and they also (22%) use artificial abortion.(ABSTRACT TRUNCATED AT 250 WORDS)