Ambulatory arterial stiffness index and carotid intima-media thickness in hypertensive rheumatoid patients: a comparative cross-sectional study.

AIM: Rheumatoid arthritis is associated with accelerated atherosclerosis. However, little is known about preclinical atherosclerosis in hypertensive rheumatoid arthritis patients. In this cross-sectional study we assessed the expression of preclinical atherosclerosis in hypertensive rheumatoid arthritis patients in comparison with matched hypertensive non-rheumatoid arthritis patients. METHODS: The study included 52 hypertensive rheumatoid arthritis patients and 42 hypertensive non-rheumatoid arthritis patients. The patients were extensively examined clinically and laboratory tested. The expression of preclinical atherosclerosis was estimated by assessing ambulatory arterial stiffness index and common carotid intima-media thickness. RESULTS: Arterial stiffness index and common carotid intima-media thickness were higher in hypertensive rheumatoid arthritis patients than in hypertensive non-rheumatoid arthritis patients. There was no correlation between arterial stiffness index and common carotid intima-media thickness with markers of inflammation and disease activity in hypertensive rheumatoid arthritis patients. CONCLUSION: The expression of subclinical atherosclerosis is more pronounced in hypertensive rheumatoid arthritis than in hypertensive non- rheumatoid arthritis patients.

The forthcoming era of precision medicine.

The aim of this essay is to present the definition and principles of personalized or precision medicine, the perspective and barriers to its development and clinical application. The implementation of precision medicine in health care requires the coordinated efforts of all health care stakeholders (the biomedical community, government, regulatory bodies, patients' groups). Particularly, translational research with the integration of genomic and comprehensive data from all levels of the organism ("big data"), development of bioinformatics platforms enabling network analysis of disease etiopathogenesis, development of a legislative framework for handling personal data, and new paradigms of medical education are necessary for successful application of the concept of precision medicine in health care. CONCLUSION: In the present and future era of precision medicine, the collaboration of all participants in health care is necessary for its realization, resulting in improvement of diagnosis, prevention and therapy, based on a holistic, individually tailored approach.

Telomerase activity in breast cancer patients: association with poor prognosis and more aggressive phenotype.

Telomerase expression is an important mechanism of tumor unlimited replicative potential. The aim of this study was to evaluate prognostic impact of telomerase activity in breast cancer patients and to correlate telomerase activity with established prognostic factors. We analyzed tissue of 102 malignant breast lesions and 20 healthy breast tissues. Telomerase activity was determined by telomeric repeat amplification protocol assay. Telomerase activity was present in 77 (75.49 %) of 102 breast cancers. Telomerase activity in breast cancers was statistically significantly higher in comparison with the activity in normal breast tissue. The levels of telomerase activity were significantly positively correlated with tumor size, axillary nodal status, histological grade, HER-2/neu protein expression in tumor tissue and expression of the nuclear antigen Ki-67. A statistically significant negative correlation was found between the presence of ER and telomerase activity. There was no correlation between telomerase activity and concentration of PR or the age of patients. Kaplan-Meier analysis showed that patients with higher telomerase activity had significantly shorter 10-year disease-free survival (p < 0.0001) and 10-year overall survival (p < 0.0001) than those with lower telomerase activity. These results were confirmed by logistic regression analysis. Our results support the prognostic role of telomerase activity and its relationship with the more aggressive phenotype of breast cancer.

Differences in the prevalence and characteristics of metabolic syndrome in rheumatoid arthritis and osteoarthritis: a multicentric study.

The purpose of the study was to examine whether rheumatoid arthritis (RA) patients have higher prevalence of metabolic syndrome (MetS) than osteoarthritis (OA) patients in association with a higher level of chronic systemic inflammation in rheumatoid arthritis. A total of 583 RA and 344 OA outpatients were analyzed in this multicentric study. Metabolic syndrome was defined using the National Cholesterol Education Program Adult Treatment Panel III criteria. A 1.6-fold higher prevalence of MetS was found in patients with OA compared with the RA patients. Among the parameters of MetS, patients with OA had significantly higher levels of waist circumference, systolic blood pressure, fasting blood glucose and triglycerides, whereas HDL cholesterol and diastolic blood pressure values were similar in both groups of patients. Higher values of inflammatory markers [C-reactive protein (CRP), erythrocyte sedimentation rate (ESR)] in MetS than in non-MetS patients and higher prevalence of MetS in patients with CRP level ≥5 mg/L in both RA and OA patients were found. In multivariate logistic regression analysis, significant predictors of MetS were type of arthritis (OA vs. RA; OR 2.5 [95 % CI 1.82-3.43]), age (OR 1.04 [95 % CI 1.03-1.06]) and ESR (OR 1.01; [95 % CI 1.00-1.01]). The significant association between OA and MetS was maintained in the regression model that controlled for body mass index (OR 1.87 [95 % CI 1.34-2.61]). The present analysis suggests that OA is associated with an increased risk of MetS, which may be due to a common underlying pathogenic mechanism.

Is the prevalence of arterial hypertension in rheumatoid arthritis and osteoarthritis associated with disease?

In this study, we compare the prevalence of arterial hypertension (HT) in rheumatoid arthritis (RA) and osteoarthritis (OA) patients, exposed to high- and low-grade chronic inflammation, respectively, to assess the possible association between chronic inflammation and HT. A total of consecutive 627 RA and 352 OA patients were enrolled in this multicentric study. HT was defined as a systolic blood pressure (BP) ≥ 140 and/or diastolic BP ≥ 90 mmHg or current use of any antihypertensive drug. Overweight/obesity was defined as body mass index (BMI) ≥ 25, and patients ≥65 years were considered elderly. The prevalence of HT was higher in the OA group than in the RA group [73.3 % (95 % CI, 68.4, 77.7) and 59.5 % (95 % CI, 55.6, 68.4) P < 0.001, respectively]. When the results were adjusted for age and BMI, the HT prevalence was similar in both groups [RA 59 % (95 % CI, 55.1, 63.8) OA 60 % (95 % CI, 58.4, 65.0)]. In both groups, the prevalence of HT was higher in the elderly and those who were overweight than in the younger patients and those with a BMI < 25. Overweight (BMI ≥ 25) and age ≥65 were independent predictors of HT in multivariate logistic regression model, which showed no association between HT and the disease (RA or OA). The results indicate a robust association of age and BMI with HT prevalence in both RA and OA. The difference in HT prevalence between RA and OA is due rather to age and BMI than to the features of the disease, putting into question specific association of HT with RA.

Cyclic adenosine 5'-monophosphate in synovial fluid of rheumatoid arthritis and osteoarthritis patients.

The relationship between synovial fluid (SF) cAMP level and IL-18 and PGE2 SF levels in rheumatoid arthritis (RA) and osteoarthritis (OA) patients, and between SF cAMP level and disease as well as inflammatory activity in RA were investigated in 17 RA and 19 OA patients. Erythrocyte sedimentation rate (ESR), serum (S) C-reactive protein (CRP) level and SF IL-18 level were higher in RA than in OA patients. SF PGE2 level was similar in both groups. SF cAMP level was higher in OA than in RA patients. In RA patients, SF cAMP level showed negative correlation with Disease Activity Score including a 28-joint count and S CRP, ESR and SF IL-18 level. The results suggest that cAMP promotes anti-inflammatory response in RA and OA patients, which is higher in the latter. Promotion of anti-inflammatory response by cAMP elevating agents might be useful in the treatment of RA.

Interaction of humic acids with human DNA: proposed mechanisms and kinetics.

Human DNA quantification by quantitative real-time PCR (QRT-PCR) has gained great importance in forensic DNA and ancient DNA studies. However, in such samples, DNA quantification is impaired by the frequently present humic acid (HA). We have previously shown that the addition of synthetic HA inhibits QRT-PCR. In this study we investigated the possible mechanisms of HA interaction with human DNA, and kinetics of QRT-PCR inhibition. In QRT-PCR with pure human DNA and no HA added, VMAX was 40. With DNA sample containing 4 microg/mL of HA, VMAX was 30.30 while the addition of extra Taq polymerase to the same sample changed VMAX into 38.91, amplifying between 80 and 90% of input DNA. The KM/VMAX ratio in all the samples remained constant, indicating that the mechanism of HA inhibition of QRT-PCR is uncompetitive by nature. Moreover, HA shifts the human DNA melting temperature point (Tm) from 75 to 87 degrees C and inhibits DNase I-mediated DNA cleavage, most probably affecting the enzyme's activity.

Academic approach to academic medicine.

Scientific approach to academic medicine crisis would require research to provide evidence for the present state of academic medicine and future actions. The prerequisites for such a research would be clear definitions, appropriate indicators, and measuring instruments. The approach should be holistic, covering tripartite academic medicine activity: education, research, and health care.

Impact of molecular medicine on pathophysiology, medical practice, and medical education.

This article brings an overview of the influence of molecular medicine on pathophysiology, medical practice, and medical education. Various aspects of the growing impact of molecular medicine on clinical practice are discussed: diagnostic and predictive testing, gene and targeted therapy, and pharmacogenomics. Insufficient data from appropriate clinical studies and evidence-based medicine presently limit the applications of molecular medicine in clinical practice. Incorporation of conceptual and clinical aspects of molecular medicine in undergraduate and postgraduate curricula and a continuing education of medical professionals is an urgent imperative for the demands of medical care quality to be met in near future. The emphasis should be put on bedside-orientated molecular medicine. The prerequisite is translational research aimed to translate basic information into the improvement of healthcare of individual patients and the population as a whole.