Increased synovial immunohistochemistry reactivity of TGF-ß1 in erosive peripheral psoriatic arthritis.

BACKGROUND: Immune and non-immune cells contribute to the pathology of chronic arthritis, and they can contribute to tissue remodeling and repair as well as disease pathogenesis. The present research aimed to analyze inflammation and bone destruction/regeneration biomarkers in patients with psoriatic arthritis (PsA), rheumatoid arthritis (RA), osteoarthritis (OA), and ankylosing spondylitis (AS). METHODS: Samples were obtained from the inflamed knee of patients with knee arthritis who had been referred for undergoing arthroscopies. The synovial membrane was processed for pathological description, IHC analysis, and quantification of mRNA expression ratio by qRT-PCR. Serum levels of TGF-ß1, IL-23, IL-6, IL-17 A, IL-22, Dkk1, Sclerostin, BMP2, BMP4, Wnt1, and Wnt5a were measured by ELISA. All these data were analyzed and compared with the demographic, clinical, blood tests, and radiological characteristics of the patients. RESULTS: The synovial membrane samples were obtained from 42 patients for IHC, extraction, and purification of RNA for synovial mRNA expression analysis, and serum for measuring protein levels from 38 patients. IHC reactivity for TGF-ß1 in the synovial tissue was higher in patients with psoriatic arthritis (p 0.036) and was positively correlated with IL-17 A (r = 0.389, p = 0.012), and Dkk1 (r = 0.388, p = 0.012). Gene expression of the IL-17 A was higher in PsA patients (p = 0.018) and was positively correlated with Dkk1 (r = 0.424, p = 0.022) and negatively correlated with BMP2 (r = -0.396, p = 0.033) and BMP4 (r = -0.472, p = 0.010). It was observed that IHC reactivity for TGF-ß1 was higher in patients with erosive PsA (p = 0.024). CONCLUSIONS: The IHC reactivity of TGF-ß1 in synovial tissue was higher in patients with erosive psoriatic arthritis, and TGF-ß1 was in relation to higher levels of gene expression of IL-17 A and Dkk1.

Population and breast cancer patients' analysis reveals the diversity of genomic variation of the BRCA genes in the Mexican population.

Interpretation of variants of unknown significance (VUS) in genetic tests is complicated in ethnically diverse populations, given the lack of information regarding the common spectrum of genetic variation in clinically relevant genes. Public availability of data obtained from high-throughput genotyping and/or exome massive parallel sequencing (MPS)-based projects from several thousands of outbred samples might become useful tools to evaluate the pathogenicity of a VUS, based on its frequency in different populations. In the case of the Mexican and other Latino populations, several thousands of samples have been genotyped or sequenced during the last few years as part of different efforts to identify common variants associated to common diseases. In this report, we analyzed Mexican population data from a sample of 3985 outbred individuals, and additional 66 hereditary breast cancer patients were analyzed in order to better define the spectrum of common genomic variation of the BRCA1 and BRCA2 genes. Our analyses identified the most common genetic variants in these clinically relevant genes as well as the presence and frequency of specific pathogenic mutations present in the Mexican population. Analysis of the 3985 population samples by MPS identified three pathogenic mutations in BRCA1, only one population sample showed a BRCA1 exon 16-17 deletion by MLPA. This resulted in a basal prevalence of deleterious mutations of 0.10% (1:996) for BRCA1 and 11 pathogenic mutations in BRCA2, resulting in a basal prevalence of deleterious mutations of 0.276% (1:362) for BRCA2, combined of 0.376% (1:265). Separate analysis of the breast cancer patients identified the presence of pathogenic mutations in 18% (12 pathogenic mutations in 66 patients) of the samples by MPS and 13 additional alterations by MLPA. These results will support a better interpretation of clinical studies focused on the detection of BRCA mutations in Mexican and Latino populations and will help to define the general prevalence of deleterious mutations within these populations.

Prevalence, risk factors, and impact of knee pain suggesting osteoarthritis in Spain.

OBJECTIVE: To estimate the point prevalence of knee pain suggesting osteoarthritis (OA) in the adult Spanish population. Secondary objectives were to examine the distribution of associated factors, as well as to assess the impact of knee pain on quality of life and function in the general population. METHODS: A population survey was conducted in year 2000 for which 2,192 subjects over 20 years of age were selected by stratified polystage cluster sampling from the censuses of 20 towns. Trained rheumatologists administered structured interviews that permitted them to rule out the presence of rheumatic symptoms, and which included validated instruments to measure function and quality of life. We used the definition of clinical symptomatic knee OA of the American College of Rheumatology. RESULTS: The estimated prevalence of knee pain suggesting OA in the general adult population is 10.2% (95% confidence interval: 7.9-12.5). Elderly women with fewer studies and from the lower social class, as well as those subjects involved in physically demanding jobs are more frequently affected. Obesity is also an important determinant for knee pain suggesting OA. Knee pain is associated to a significant decrease in functional ability and quality of life, even after adjustment for age, sex, and comorbidity. CONCLUSION: The prevalence of knee pain suggesting OA in the general Spanish population is higher than expected, mainly related to a high rate of knee pain in women over 55. The proportion of very old persons and of those obese are important factors to take into account when comparing the rate of knee OA between populations.

Efficacy and safety of intraarticular hyaluronic acid in the treatment of hip osteoarthritis: a systematic review.

OBJECTIVE: This study sought to use a systematic review to ascertain the efficacy and safety of hyaluronic acid (HA) in the treatment of hip osteoarthritis (OA). DESIGN: A protocolized search was made of a number of electronic databases, including Medline, EMBASE, Cochrane Library and Health Technology Assessment (HTA) among others. Two independent reviewers applied a series of inclusion and exclusion criteria to the studies located in the search, and selected only those that included more than 20 patients; had a follow-up period of more than 1 week; and exclusively assessed the efficacy and/or effectiveness of HA in patients with confirmed hip OA. RESULTS: A total of eight studies, comprising clinical trials and one review, met the inclusion criteria, and had study populations ranging from 22 to 104 patients. Only two of the trials were controlled: one compared two HAs of different molecular weights; and the other compared HA with corticoids and a placebo. Relief of pain was estimated to be around 40-50% by most studies, though the duration of this post-treatment effect was not known. CONCLUSIONS: Based on available evidence, HA treatment should only be used under careful supervision by the clinician and just in those cases where other treatments have failed in hip OA. There are methodologic limitations displayed in the literature, which were mainly the absence of a control group in most of the studies, overly short follow-up periods, and different ways of measuring outcomes.