[Epidemiological study of juvenile idiopathic arthtitis in the last sixteen years in Asturias (Spain)]. / Estudio epidemiológico de artritis idiopática juvenil en el Principado de Asturias: presentación de la casuística en los últimos dieciséis años.

INTRODUCTION: Juvenile idiopathic arthritis (JIA) is one of the most common chronic diseases in children. The results of several epidemiologic studies have shown surprisingly wide variety in the incidence (0.8 to 22.6 per 100,000 children) and prevalence (7 to 400 per 100,000) of this disease. MATERIAL AND METHODS: We performed a retrospective epidemiological study to identify all patients born after 1989 and resident in Asturias who were diagnosed with JIA using the criteria of the International League of Associations for Rheumatology (ILAR) criteria. RESULTS: Data were obtained from 60 patients (23 boys and 37 girls). The mean age of symptom onset was 5.6 years, with onset of spondyloarthropathies occurring most frequently in the oldest group. An incidence rate of 2.5/10(5) (3.5 at the present time) and a prevalence rate of 51.4/10(5) children and adolescents aged less than 16 years old were calculated. In 50% of patients, JIA started with inflammation in one of the knees. The most frequent form of onset was persistent oligoarticular arthritis (41.7%), followed by spondyloarthropathies (11.7%), conditions that did not meet the criteria for any category (11.7%), polyarticular arthritis (11.7%), systemic disease (10%), psoriatic arthritis (6.7%), and extended oligoarticular arthritis (6.7%). Chronic anterior uveitis was found in 5 patients (pauciarticular group in all 5 patients). Methotrexate was used in 25 children with good response and no relevant adverse events were observed. Only 10% of our patients are currently in the active phase of arthritis. CONCLUSION: An incidence rate of 3.5/10(5) and a prevalence rate of 51.4/10(5) children and adolescents aged less than 16 years old in Asturias were calculated (taking into account the possible bias of our study). The most frequent form of onset was persistent oligoarticular arthritis and the most commonly involved joints were the knees.

Molecular staging of bladder cancer with RT-PCR assay for CK20 in peripheral blood, bone marrow and lymph nodes: comparison with standard histological staging.

BACKGROUND: The aim of this study was to analyze whether the CK20 reverse transcriptase polymerase chain reaction (RT-PCR) is suitable for detecting circulating tumor cells and residual tumor cells in lymph nodes, in patients with muscle invasive transitional cell carcinoma (TCC) of the bladder, and to compare these results with standard histological staging. PATIENTS AND METHODS: The nested RT-PCR assay was used to analyze the CK20 transcript in the peripheral blood, bone marrow, lymph nodes, the tumor and normal biopsies of bladder from 57 patients with invasive TCC of the bladder, who underwent radical cystectomy, and from 9 patients with noninvasive TCC. RESULTS: Lymph node pathological status was positive in 24 out of the 57 patients studied and all of them except I showed expression of CK20, with a correlation between histological technique and RT-PCR of 95.8%. A statistically significant correlation of lymph node CK20 RT-PCR with the standard risk factor of pathological stage (p = 0.04) was observed Blood and bone marrow CK20 RT-PCR showed no correlation with pathological stage. CONCLUSION: Lymph node CK 20 RT-PCR correlates with pathological stage in bladder cancer. The CK20 RT-PCR assay appears to be a highly sensitive and specific method for detecting circulating tumor cells and residual disease in lymph nodes in patients with invasive bladder cancer. Further evaluation of the significance of CK20 as a molecular marker for staging and follow-up in these patients is necessary.

In vitro and in vivo models for the evaluation of new inhibitors of human steroid sulfatase, devoid of residual estrogenic activity.

The goal of our research project is to develop a new class of orally active drugs, estrone sulfatase inhibitors, for the treatment of estrogen-dependent (receptor positive) breast cancer. Several compounds were synthesized and their pharmacological potencies explored. Based on encouraging preliminary results, three of them, TX 1299, TX 1492 and TX 1506 were further studied in vitro as well as in vivo. They proved to be strong inhibitors of estrone sulfatase when measured on the whole human JEG-3 choriocarcinoma and MCF-7 breast cancer cells and their IC(50)s found to be in the range of known standard inhibitors. Their residual estrogenic activity was checked as negative in the test of induction of alkaline phosphatase (APase) activity in whole human endometrial adenocarcinoma Ishikawa cells. In addition, their effect on aromatase activity in JEG-3 cells was also examined, since the goal of inhibiting both sulfatase and aromatase activities appears very attractive. However, it has been unsuccessful so far. Then, in vivo potencies of TX 1299, the lead compound in our chemical series, were evaluated in comparison with 6,6,7-COUMATE, a non-steroidal standard, in two different rat models and by oral route. First, the absence of any residual estrogenic activity for these compounds was checked in the uterotrophic model in prepubescent female rats. Second, antiuterotrophic activity in adult ovariectomized rat supplemented with estrone sulfate (E(1)S), showed that both compounds were potent inhibitors, the power of TX 1299 relative to 6,6,7-COUMATE being around 80%. This assay was combined with uterine sulfatase level determination and confirmed the complete inhibition of this enzyme within the target organ. Preliminary studies indicated that other non-steroid compounds in the Théramex series were potent in vitro and in vivo inhibitors of estrone sulfatase in rats and further studies are in progress.

Gene expression profiles in prostate cancer: identification of candidate non-invasive diagnostic markers.

OBJECTIVE: To analyze gene expression profiles of prostate cancer (PCa) with the aim of determining the relevant differentially expressed genes and subsequently ascertain whether this differential expression is maintained in post-prostatic massage (PPM) urine samples. MATERIAL AND METHODS: Forty-six tissue specimens (36 from PCa patients and 10 controls) and 158 urine PPM-urines (113 from PCa patients and 45 controls) were collected between December 2003 and May 2007. DNA microarrays were used to identify genes differentially expressed between tumour and control samples. Ten genes were technically validated in the same tissue samples by quantitative RT-PCR (RT-qPCR). Forty two selected differentially expressed genes were validated in an independent set of PPM-urines by qRT-PCR. RESULTS: Multidimensional scaling plot according to the expression of all the microarray genes showed a clear distinction between control and tumour samples. A total of 1047 differentially expressed genes (FDR≤.1) were indentified between both groups of samples. We found a high correlation in the comparison of microarray and RT-qPCR gene expression levels (r=.928, P<.001). Thirteen genes maintained the same fold change direction when analyzed in PPM-urine samples and in four of them (HOXC6, PCA3, PDK4 and TMPRSS2-ERG), these differences were statistically significant (P<.05). CONCLUSION: The analysis of PCa by DNA microarrays provides new putative mRNA markers for PCa diagnosis that, with caution, can be extrapolated to PPM-urines.

[Poverty and disease: users of the primary care social services of a primary care center]. / Pobreza y enfermedad: usuarios de los servicios sociales de atención primaria de un centro de atención primaria.

OBJECTIVES: To find the individual and socio-family characteristics of that sector of the population which uses Primary Care Social Services (PCSS) at the Primary Care Centre (PCC) and the social problems which occasion demand. DESIGN: A retrospective descriptive study, based on checking over social work case files. SETTING: A PCC situated in Barcelona's second industrial belt, serving a population with a low socio-economic level. PARTICIPANTS: The population group under study were the users with social work files open from January 1st 1985 to July 31st 1991 (a total of 690 case histories). A representative sample of 296 was selected. MEASUREMENTS AND MAIN RESULTS: In comparison with the population of the basic Health Area, the user population of the PCSS at the PCC was predominantly women, and had an older average age, a higher proportion of divorce/separation and widowhood, and, in the labour context, higher unemployment and retirement. A high proportion of one-parent families (12.8%) was found. Analysis of the work situation showed that 50% of the workers were temporary and 75% of the unemployed received no benefit. 51% of the retired people received the minimum pension and 11% received no pension. Monthly family income, recorded for 46.5% of the cases, was 75,362 pesetas (SD 37,643). The most common problems were those related to the "HEALTH" section (61%). CONCLUSIONS: The user population of the PCSS at the PCC is, in socio-economic terms, deteriorated, a condition closely related to the development of chronic illnesses. Tackling health inequalities from Primary Care is under discussion.

Chromosomal high-polysomies predict tumour progression in T1 transitional cell carcinoma of the bladder.

UNLABELLED: The main prognostic factor generally accepted for tumour progression in T1 transitional cell carcinoma (TCC) of the bladder is histological grade. Despite this fact it is considered inaccurate to make clinical decisions on individuals. It appears that progression from minimally invasive to deeply invasive cancer is concurrent with the acquisition of genomic alterations that increase the malignant potential of cancer cells. The aim of this study is to determine if changes in chromosomes 7, 8, 9 and 17 copy number can be used to predict recurrence and progression in patients with T1 TCC of the urinary bladder. METHODS: Thirty-one T1 TCC samples were analyzed for chromosomal alterations by fluorescence in situ hybridization using centromeric probes for chromosomes 7, 8, 9 and 17. Clinical data were collected from the patients' clinical records and correlated with chromosomal studies. RESULTS: Histological grade was confirmed as a prognostic factor of tumour progression (p=0.01). None of the cytogenetic alterations demonstrated in the studied group could be related to tumour recurrence. The high-polysomies (five or more copies) of chromosomes 8, 9 and 17 showed predictive value (p=0.05, 0.05, 0.03 respectively) for tumour progression since it was observed that patients with high-polysomy of these chromosomes showed more risk of tumour progression towards muscle-invasive disease than those without high-polysomy alteration. CONCLUSION: Our findings suggest a possible prognostic significance of highly aneuploid cells (high-polysomies of chromosomes 8, 9 and 17) in tumour progression of T1 TCC bladder tumours. FISH analysis is a reproducible technique for evaluating cytogenetic alterations and could contribute to the assessment of the individual prognosis of T1 transitional cell carcinoma of the bladder.