José Vaz Patto

Portuguese Institute of Rheumatology, Lisboa, Lisbon, Portugal

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Publications (25)44.24 Total impact

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    ABSTRACT: To investigate whether CCR5 deletion is associated with susceptibility to Behçet's disease (BD) in a Portuguese population.
    Clinical and experimental rheumatology 09/2014; 32 Suppl 84(4):72-74. · 2.66 Impact Factor
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    ABSTRACT: Behçet's disease (BD) is a rare chronic vasculitis of unclear etiology. It has been suggested that inflammatory response has an important role in BD pathophysiology. Herein, we aimed to study the interplay between inflammation, iron metabolism and endothelial function in BD and search for its putative association with disease activity. Twenty five patients clinically diagnosed with BD were selected and twenty four healthy age-sex matched individuals participated as controls. Results showed an increase of total number of circulating white blood cells and neutrophils, serum transferrin, total iron binding capacity, mieloperoxidase (MPO), ceruloplasmin (Cp), C reactive protein, β2 microglobulin and Cp surface expression in peripheral blood monocytes in BD patients comparatively to healthy individuals (p < 0,05). Of notice, the alterations observed were associated to disease activity status. No significant differences between the two groups were found in serum nitric oxide concentration. The results obtained suggest an important contribution from innate immunity in the pathogenesis of this disease. In particular, surface expression of leukocyte-derived Cp may constitute a new and relevant biomarker to understand BD etiology.
    Clinical hemorheology and microcirculation 04/2014; 56:175-185. · 3.40 Impact Factor
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    ABSTRACT: AimTo explain the missing heritability after the genome-wide association studies era, sequencing studies allow the identification of low-frequency variants with a stronger effect on disease risk. Common variants in the interleukin 10 gene (IL10) have been consistently associated with Behçet's disease (BD) and the goal of this study is to investigate the role of low-frequency IL10 variants in BD susceptibility.Methods To identify IL10 low-frequency variants, a discovery group of 50 Portuguese BD patients were Sanger-sequenced in a 7.7 kb genomic region encompassing the complete IL10 gene, 0.9 kb upstream and 2 kb downstream, and two conserved regions in the putative promoter. To assess if the novel variants are BD- and/or Portuguese-specific, they were assayed in an additional group of BD patients (26 Portuguese and 964 Iranian) and controls (104 Portuguese and 823 Iranian).ResultsRare IL10 coding variants were not detected in BD patients, but we identified 28 known single nucleotide polymorphisms with minor allele frequencies ranging from 0.010 to 0.390, and five novel non-coding variants in five heterozygous cases. ss836185595, located in the IL10 3′ untranslated region, was also detected in one Iranian control individual and therefore is not specific to BD. The remaining novel IL10 variants (ss836185596 and ss836185602 in intron 3, ss836185598 and ss836185604 in the putative promoter region) were not found in the replication dataset.Conclusion This study highlights the importance of screening the whole gene and regulatory regions when searching for novel variants associated with complex diseases, and the need to develop bioinformatics tools to predict the functional impact of non-coding variants and statistical tests which incorporate these predictions.
    International Journal of Rheumatic Diseases 04/2014; · 1.65 Impact Factor
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    ABSTRACT: Behçet's disease (BD) is a complex disease with genetic and environmental risk factors implicated in its etiology; however, its pathophysiology is poorly understood. To decipher BD's genetic underpinnings, we combined gene expression profiling with pathway analysis and association studies. We compared the gene expression profiles in peripheral blood mononuclear cells (PBMCs) of 15 patients and 14 matched controls using Affymetrix microarrays and found that the neuregulin signaling pathway was over-represented among the differentially expressed genes. The Epiregulin (EREG), Amphiregulin (AREG), and Neuregulin-1 (NRG1) genes of this pathway stand out as they are also among the top differentially expressed genes. Twelve haplotype tagging SNPs at the EREG-AREG locus and 15 SNPs in NRG1 found associated in at least one published BD genome-wide association study were tested for association with BD in a dataset of 976 Iranian patients and 839 controls. We found a novel association with BD for the rs6845297 SNP located downstream of EREG, and replicated three associations at NRG1 (rs4489285, rs383632, and rs1462891). Multifactor dimensionality reduction analysis indicated the existence of epistatic interactions between EREG and NRG1 variants. EREG-AREG and NRG1, which are members of the epidermal growth factor (EGF) family, seem to modulate BD susceptibility through main effects and gene-gene interactions. These association findings support a role for the EGF/ErbB signaling pathway in BD pathogenesis that warrants further investigation and highlight the importance of combining genetic and genomic approaches to dissect the genetic architecture of complex diseases.
    Journal of Molecular Medicine 04/2013; · 4.77 Impact Factor
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    ABSTRACT: OBJECTIVE: Behçet's disease (BD) is a chronic, relapsing, inflammatory vascular disease with no pathognomonic test. Low sensitivity of the currently applied International Study Group (ISG) clinical diagnostic criteria led to their reassessment. METHODS: An International Team for the Revision of the International Criteria for BD (from 27 countries) submitted data from 2556 clinically diagnosed BD patients and 1163 controls with BD-mimicking diseases or presenting at least one major BD sign. These were randomly divided into training and validation sets. Logistic regression, 'leave-one-country-out' cross-validation and clinical judgement were employed to develop new International Criteria for BD (ICBD) with the training data. Existing and new criteria were tested for their performance in the validation set. RESULTS: For the ICBD, ocular lesions, oral aphthosis and genital aphthosis are each assigned 2 points, while skin lesions, central nervous system involvement and vascular manifestations 1 point each. The pathergy test, when used, was assigned 1 point. A patient scoring ≥4 points is classified as having BD. In the training set, 93.9% sensitivity and 92.1% specificity were assessed compared with 81.2% sensitivity and 95.9% specificity for the ISG criteria. In the validation set, ICBD demonstrated an unbiased estimate of sensitivity of 94.8% (95% CI: 93.4-95.9%), considerably higher than that of the ISG criteria (85.0%). Specificity (90.5%, 95% CI: 87.9-92.8%) was lower than that of the ISG-criteria (96.0%), yet still reasonably high. For countries with at least 90%-of-cases and controls having a pathergy test, adding 1 point for pathergy test increased the estimate of sensitivity from 95.5% to 98.5%, while barely reducing specificity from 92.1% to 91.6%. CONCLUSION: The new proposed criteria derived from multinational data exhibits much improved sensitivity over the ISG criteria while maintaining reasonable specificity. It is proposed that the ICBD criteria to be adopted both as a guide for diagnosis and classification of BD.
    Journal of the European Academy of Dermatology and Venereology 02/2013; · 2.69 Impact Factor
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    ABSTRACT: Independent replication of the findings from genome-wide association studies (GWAS) remains the gold standard for results validation. Our aim was to test the association of Behçet's disease (BD) with the interleukin-10 gene (IL10) and the IL-23 receptor-IL-12 receptor β2 (IL23R-IL12RB2) locus, each of which has been previously identified as a risk factor for BD in 2 different GWAS. Six haplotype-tagging single-nucleotide polymorphisms (SNPs) in IL10 and 42 in IL23R-IL12RB2 were genotyped in 973 Iranian patients with BD and 637 non-BD controls. Population stratification was assessed using a panel of 86 ancestry-informative markers. Subtle evidence of population stratification was found in our data set. In IL10, rs1518111 was nominally associated with BD before and after adjustment for population stratification (odds ratio [OR] for T allele 1.20, 95% confidence interval [95% CI] 1.02-1.40, unadjusted P [P(unadj) ] = 2.53 × 10(-2) ; adjusted P [P(adj) ] = 1.43 × 10(-2) ), and rs1554286 demonstrated a trend toward association (P(unadj) = 6.14 × 10(-2) ; P(adj) = 3.21 × 10(-2) ). Six SNPs in IL23R-IL12RB2 were found to be associated with BD after Bonferroni correction for multiple testing, the most significant of which were rs17375018 (OR for G allele 1.51, 95% CI 1.27-1.78, P(unadj) = 1.93 × 10(-6) ), rs7517847 (OR for T allele 1.48, 95% CI 1.26-1.74, P(unadj) = 1.23 × 10(-6) ), and rs924080 (OR for T allele 1.29, 95% CI 1.20-1.39, P = 1.78 × 10(-5) ). SNPs rs10489629, rs1343151, and rs1495965 were also significantly associated with BD in all tests performed. Results of meta-analyses of our data combined with data from other populations further confirmed the role of rs1518111, rs17375018, rs7517847, and rs924080 in the risk of BD, but no epistatic interactions between IL10 and IL23R-IL12RB2 were detected. Results of imputation analysis highlighted the importance of IL23R regulatory regions in the susceptibility to BD. These findings independently confirm, extend, and refine the association of BD with IL10 and IL23R-IL12RB2. These associations warrant further validation and investigation in patients with BD, as they may have implications for the development of novel therapies (e.g., immunosuppressive therapy targeted at IL-23p19).
    Arthritis & Rheumatology 02/2012; 64(8):2761-72. · 7.48 Impact Factor
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    ABSTRACT: To generate and validate at pretest level a cross-culturally adapted Portuguese version of Xerostomia Inventory (XI), a 11-item questionnaire designed to measure specific xerostomia rating of patients complaints. The original English version of the XI was translated into Portuguese following the guidelines for cross-cultural adaptation of health-related quality of life measures. Thirty patients with primary Sjögren syndrome were recruited for this study. The questionnaires were administered by trained and calibrated dental doctors to each patient. XI properties were examined including reliability, internal consistency, and test-retest reliability, using Cronbach's alpha, total and inter-item correlation, and intra-class correlation coefficients (ICC), respectively. Construct validity supported by objective measurements of xerostomia intra-oral signs and salivary secretion was investigated. Alpha was set at 0.05. Informed consents and local ethical committee clearance were obtained. Internal consistency and test-retest reliability were excellent (Cronbach's α=0.9; ICC range=0.79-0.94). Scatterplot interpolation and Pearson correlation coefficient suggested the presence of a strong, negative, and significant correlation between salivation and the XI scores indicating construct validity. The Portuguese version of the XI can be considered a reliable and valid instrument to measure patients' xerostomia symptoms.
    Oral Diseases 11/2011; 18(3):293-8. · 2.38 Impact Factor
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    ABSTRACT: The authors present the revised version of the Portuguese Society of Rheumatology (SPR) guidelines for the treatment of Rheumatoid Arthritis (RA) with biological therapies. In these guidelines the criteria for introduction and maintenance of biological agents are discussed as well as the contraindications and procedures in the case of nonresponders. Biological treatment (with a tumour necrosis factor antagonist, abatacept or tocilizumab) should be considered in RA patients with a disease activity score 28 (DAS 28) equal to or greater than 3.2 despite treatment with at least 20mg-weekly-dose of methotrexate (MTX) for at least 3 months or, if such treatment is not possible, after 3 months of other conventional disease modifying drug or combination therapy. A DAS 28 score between 2.6 and 3.2 with a significant functional or radiological deterioration under treatment with conventional regimens could also constitute an indication for biological treatment. The treatment goal should be remission or, if that is not achievable, at least a low disease activity, defined by a DAS28 lower than 3.2, without significative functional or radiological worsening. The response criteria, at the end of the first 3 months of treatment, are a decrease of at least 0.6 in the DAS28 score. After 6 months of treatment res­ponse criteria is defined as a decrease greater than 1.2 in the DAS28 score. Non-responders, in accordance to the Rheumatologist’s clinical opinion, should try a switch to another biological agent (tumour necrosis factor antagonist, abatacept, rituximab or tocilizumab).
    Acta reumatologica portuguesa 10/2011; 36(4):385-8. · 0.70 Impact Factor
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    ABSTRACT: To compare salivary pH changes and stimulation efficacy of two different gustatory stimulants of salivary secretion (GSSS) in patients with primary Sjögren syndrome. Portuguese Institute for Rheumatological Diseases. Double-blind randomized controlled trial. Eighty patients were randomized to two intervention groups. Sample size was calculated using an alpha error of 0.05 and a beta of 0.20. Participants were randomly assigned to receive a new GSSS containing a weaker malic acid, fluoride and xylitol or a traditionally citric acid-based one. Saliva collection was obtained by established methods at different times. The salivary pH of the samples was determined with a pH meter and a microelectrode. Salivary pH variations and counts of subjects with pH below 4.5 for over 1 min and stimulated salivary flow were the main outcome measures. Both GSSS significantly stimulated salivary output without significant differences between the two groups. The new gustatory stimulant of salivary secretion presented an absolute risk reduction of 52.78% [33.42-72.13 (95% CI)] when compared with the traditional one. In Xerostomic Primary Sjögren syndrome patients, gustatory stimulants of salivary secretion based on acid mail only with fluoride and xylitol present similar salivary stimulation capacity when compared to citric acid-based ones, besides significantly reducing the number of salivary pH drops below 4.5. This could be related to a diminished risk for dental erosion and should be confirmed with further studies.
    Journal of Oral Pathology and Medicine 04/2011; 40(10):785-92. · 2.06 Impact Factor
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    ABSTRACT: Objectives: To generate and validate a cross culturally adapted Portuguese version of the xerostomia Inventory (XI) a 12 item questionnaire designed to measure specific xerostomia rating of patients complaints. Methods: This was a pilot study in which the original English version of the XI was translated into Portuguese following the guidelines for cross-cultural adaptation of health-related quality of life measures. 30 patients with primary Sjogren syndrome (PSS) attending the Portuguese Institute for Reumathological Diseases were recruited for this study. The questionnaires were administered by trained and calibrated dental doctors twice to each patient within a two week interval. Resulting XI properties were examined including reliability, internal consistency, and test-retest reliability, using Cronbach's alpha, total and inter item correlation, and intraclass correlation coefficients (ICC), respectively. Further, construct validity supported by objective measurements of xerostomia intra oral signs and salivary secretion, was established by calculating ANOVA. Alpha was set at 0.05. Informed consents and local ethical committee clearance were obtained. Results: Internal consistency and test-retest reliability were excellent (Cronbach's alpha= 0,925 ; ICC range= 0,68-0,94). In addition, all associations were significant and in the expected direction. Conclusion: This pilot study indicates that the Portuguese version of the XI questionnaire may be considered a reliable and valid instrument to measure specific xerostomia rating of patients complaints.
    03/2011
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    ABSTRACT: Objectives:To compare salivary stimulation and pH changes of two different Gustatory Stimulants of Salivation (GSSS) (XerosTM) (malic acid 4.33% w/w) and (SST) (malic acid 4.2% and citric acid 2.1% w/w) in patients with Primary Sjgren Syndrome (PSS). Methods:Double blind two arm parallel RCT. 40 patients with PSS attending the Portuguese Institute for Reumathological Diseases were randomized to one of two groups: Xeros (N) or SST (C). Unstimulated, mechanical and GSSS stimulated whole saliva flow rate and pH were measured by previously established methods. Time of GSSS induced pH drop below 4.5 was expressed in minutes as the mean 95% confidence interval. To better quantify risk differences of GSSS induced pH drop below 4.5 a contingency table compiling the counts of subjects with pH drops below 4.5 for over one minute was obtained (TSB), absolute risk reduction (ARR) and number needed to treat (NNT) were also calculated. Means of salivary flow, salivary pH and time of pH drop below 4.5 were analysed with paired or independent Student's t-test or ANOVA and post hoc tests as appropriate. Informed consents and local ethical committee clearance was obtained. Results:No significant differences were found for salivation parameters, but pH drop levels during the GSSS dissolution yielded significant differences between the two groups. The N group presented an ARR of 75% [46.49- 87.62 95% CI]. For TSB values over 1 min when compared with the C group the NNT was 2 (1-2 95% CI), meaning that for each two patients who took lozenge from the N group GSSS an episode of TSB over 1 min was avoided. Conclusions:The results of this study suggest that malic acid based GSSS increases salivary secretion with same magnitude but is safer regarding dental erosion when compared with a traditional citric based GSSS. Study supported by Dentaid Corporation.
    IADR General Session 2011; 03/2011
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    ABSTRACT: Objectives: To compare salivary stimulation and pH changes of a Gustatory Stimulant of Salivation (SST) (malic acid 4.2% and citric acid 2.1% w/w) in healthy volunteers and patients with Primary Sjgren Syndrome (PSS) Methods: 30 healthy volunteers and 30 patients with PSS attending the Portuguese Institute for Reumathological Diseases or the Dental Clinic of a Portuguese University were to assigned to one of two groups according the presence or not of PSS: PSS Group (N) or Healthy Group (C). Unstimulated, mechanical and GSSS stimulated whole saliva flow rate and pH were measured by previously established methods. Time of GSSS induced pH drop below 4.5 was expressed in minutes as the mean 95% confidence interval. To better quantify risk differences of GSSS induced pH drop below 4.5 a contingency table compiling the counts of subjects with pH drops below 4.5 for over one minute was obtained (TSB), absolute risk increase (ARI) and number needed to harm (NNH) were also calculated. Means of salivary flow, salivary pH and time of pH drop below 4.5 were analysed with paired or independent Student's t-test or ANOVA and post hoc tests as appropriate. Informed consents and local ethical committee clearance was obtained. Results: Significant differences were found for all parameters except unstimulated whole saliva pH. The PSS group presented a significant decrease for mechanical and GSSS stimulated salivary secretion and a significant increase in time of GSSS induced pH drop below 4.5 when compared to the N Group.. For TSB values over 1 min when compared to the healthy patients group the ARI was of 14% and the NNH was 8. Conclusions: The results of this study suggest that PSS exerts a negative effect on saliva secretion and on the ability to counteract salivary pH drop stimulus.
    03/2011
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    ABSTRACT: The authors present the revised version of the Portuguese Society of Rheumatology (SPR) guidelines for the treatment of rheumatoid arthritis (RA) with biological therapies. In these guidelines the criteria for introduction and maintenance of biological agents are discussed as well as the contraindications and procedures in the case of non-responders. Biological treatment should be considered in RA patients with a disease activity score 28 (DAS 28) superior to 3.2 despite treatment with 20mg/week of methotrexate (MTX) for at least 3 months or, if such treatment is not possible, after 6 months of other conventional disease modifying drug or combination therapy. A DAS 28 score between 2.6 and 3.2 with a significant functional or radiological deterioration under treatment with conventional regimens could also constitute an indication for biological treatment. The treatment goal should be remission or, if that is not achievable, at least a low disease activity, characterized by a DAS28 lower than 3.2, without significative functional or radiological worsening. The response criteria, at the end of the first 3 months of treatment, are a decrease of 0.6 in the DAS28 score. After 6 months of treatment response criteria is defined as a decrease of more than 1.2 in the DAS28 score. Non-responders, in accordance to the Rheumatologist's clinical opinion, should try a switch to another biological agent (tumour necrosis factor antagonist, abatacept, rituximab or tocilizumab).
    Acta reumatologica portuguesa 01/2010; 35(1):95-8. · 0.70 Impact Factor
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    ABSTRACT: To evaluate the applicability and utility of unstimulated syalometry and instruments of evaluation of sicca complaints in a Sjögren's syndrome outpatient clinic. We performed unstimulated syalometry to 45 consecutive Primary Sjögren's Syndrome patients (PSS) and 21 healthy asymptomatic individuals age and sex-matched. PSS patients were further evaluated with Schirmer's test. We applied 3 published questionnaires to PSS patients: Xerostomia Inventory (XI), Oral Health Impact Profile-short form (OHIP) and Ocular Surface Disease Index (OSDI), and correlated the results with syalometry and Schirmer's test. Statistical analysis was performed with SPSS (Mann-Whitney U-test and Spearman's correlation). Salivary flux was significantly lower in PSS patients, as compared to controls (0.08+/-0.01 ml/min versus 0.38+/-0.25 ml/min, p=0.000), and decreased with age. Syalometry didn't correlate with Schirmer's test. OHIP scores (mean 26.8 points, ranging from 2 to 43 for a maximum of 56 points) didn't correlate with syalometry neither with Schirmer's test, but showed an association with the XI (p<0.0005) and OSDI (p<0.0005) tests. The XI questionnaire (mean 28.4 points, ranging from 11 to 41 for a maximum of 44 points) correlated with syalometry (p=0.018), with the OHIP questionary (p<0.0005) and with the OSDI scale (p=0.004), although it didn't correlate with Schirmer's test. OSDI scores (mean 56.5 points, ranging from 7 to 90 for a maximum of 100 points) didn't correlate with Schirmer's test neither with syalometry, but associated with the XI (p=0.004) and OHIP (p<0.0005) scales. Unstimulated syalometry is useful in the evaluation of patients suspected of suffering from Sjögren's syndrome, since it can confirm salivary hypofunction in a quick and cheap manner, allowing to differentiate between healthy individuals and patients. In a specialized clinic, the immediate availability of a salivary functional test is important in the classification of PSS or sicca syndrome. The xerostomia and xerophtalmia impact scales were mutually concordant, and since they evaluate the effects of the disease through time, could be helpful in our daily consultation.
    Acta reumatologica portuguesa 01/2009; 34(2A):212-8. · 0.70 Impact Factor
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    ABSTRACT: Human leukocyte antigen (HLA)-B*51 is a well-known genetic factor associated with Behçet's disease (BD). To analyse the influence of HLA-B*51 and other HLA class I alleles in BD susceptibility in a Portuguese population and its association with disease severity, we studied 78 BD patients and 208 healthy controls. The patients were classified into two severity groups as described by Gul et al. As expected, a higher frequency of HLA-B*51 was found. The frequency of HLA-Cw*16 alleles was significantly higher in patients. Regarding severity, HLA-B*27 frequency was higher in the severe group compared with controls and with the mild group. Thus, HLA-B*51 and HLA-Cw*16 seem to confer susceptibility to BD in this patients. HLA-B*27 may be important as a prognostic factor.
    Tissue Antigens 10/2008; 72(4):379-82. · 2.93 Impact Factor
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    ABSTRACT: The objective of this study was to assess whether clinical measures of rheumatoid arthritis activity and severity were influenced by tumor necrosis factor-alpha (TNF-alpha) promoter genotype/haplotype markers. Each patient's disease activity was assessed by the disease activity score using 28 joint counts (DAS28) and functional capacity by the Health Assessment Questionnaire (HAQ) score. Systemic manifestations, radiological damage evaluated by the Sharp/van der Heijde (SvdH) score, disease-modifying anti-rheumatic drug use, joint surgeries, and work disability were also assessed. The promoter region of the TNF-alpha gene, between nucleotides -1,318 and +49, was sequenced using an automated platform. Five hundred fifty-four patients were evaluated and genotyped for 10 single-nucleotide polymorphism (SNP) markers, but 5 of these markers were excluded due to failure to fall within Hardy-Weinberg equilibrium or to monomorphism. Patients with more than 10 years of disease duration (DD) presented significant associations between the -857 SNP and systemic manifestations, as well as joint surgeries. Associations were also found between the -308 SNP and work disability in patients with more than 2 years of DD and radiological damage in patients with less than 10 years of DD. A borderline effect was found between the -238 SNP and HAQ score and radiological damage in patients with 2 to 10 years of DD. An association was also found between haplotypes and the SvdH score for those with more than 10 years of DD. An association was found between some TNF-alpha promoter SNPs and systemic manifestations, radiological progression, HAQ score, work disability, and joint surgeries, particularly in some classes of DD and between haplotypes and radiological progression for those with more than 10 years of DD.
    Arthritis research & therapy 02/2007; 9(2):R37. · 4.27 Impact Factor
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    ABSTRACT: Rheumatic patients with chronic pain describe in a vivid way the influence of climate on pain and disease activity. Several studies seem to confirm this association. To evaluate and compare in a population of rheumatic patients the perceived influence of weather changes on pain and disease activity This is a retrospective cross-sectional study. For three weeks an assisted self-reported questionnaire with nine dimensions and a VAS pain scale was performed on consecutive out-patients in our clinic. 955 patients 787 female 168 male mean age 57.9 years with several rheumatologic diagnosis were evaluated. Overall 70 of the patients believed that the weather influenced their disease and 40 believed that the influence was high. Morning stiffness was influenced in 54 high influenced in 34 . Autumn and Winter were the most influential periods as well as humidity 67 and low temperatures 59 . In our study as well as in literature we found that a high percentage of patients 70 perceived that weather conditions influenced their pain and disease. Fibromyalgia patients seemed to be strongly influenced by weather changes. Our study confirms that patients perception on the influence of climate on pain and therefore their disease is an important clinical factor and it should be considered when evaluating rheumatic patients.
    Acta reumatologica portuguesa 01/2007; 32(4):351-61. · 0.70 Impact Factor
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    ABSTRACT: In Portugal, 13 cases of tuberculosis (TB) were reported, in the period between 1999 and 2005, in 960 patients exposed to anti-TNFalpha treatment (1.35%), 8 females and 5 males. Mean age was 46.7 +/- 13.8 years. 9 patients had rheumatoid arthritis (RA), in 639 exposed patients (1.4%), 3 had ankylosing spondylitis (AS), in 200 exposed patients (1.5%) and 1 had psoriatic arthritis (PA), in 101 exposed patients (1%). The anti-TNFa used was in 8 cases infliximab (in 456 patients exposed, 1.5%), in 4 adalimumab (in 171 patients exposed, 2.3%) and in 1 etanercept (in 333 exposed, 0.3%). Treatment with a biological agent was started 11.1 +/- 8.7 months (min 3 and max 50) before TB onset. Tuberculin skin test (TST) was performed in 9 out of the 13 patients (the other 4 had started biological therapy before 2002). In 3 cases the TST response was 0 mm, in 3 less than 10 mm, in one was 14 mm and in two 20 mm. In the 3 cases with a TST response superior to 10 mm, isoniazid treatment 300 mg/d was prescribed, during 9 months. The time between first symptoms and TB diagnosis was 2.6 +/- 2.9 months. TB involvement was pulmonary in 6 patients, lymph node disease in 2, peritoneal and pulmonary in 2, osteoarticular in one case, lymph node disease and splenic in another and miliar TB in the last case. One death was reported; all of the other cases had a good outcome after anti-TB treatment. In two cases (one treated with adalimumab and the other with infliximab), paradoxical response to treatment occurred. None of the patients has restarted biological therapy after TB treatment.
    Acta reumatologica portuguesa 01/2006; 31(3):247-53. · 0.70 Impact Factor
  • Atherosclerosis 01/2000; 151(1):316-316. · 3.71 Impact Factor
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    ABSTRACT: Introduction. The presence of autoantibodies (Abs) and focal sialoadenitis on labial salivary gland biopsies (LSGB) are considered to be the most specific disease markers in Sjögren's Syndrome (SS). LSGB are time consuming and thus the presence of Abs has increasingly served as a criterion in clinical rheumatologic practice. The aims of our study were to investigate if there is an associa- tion between a histologic diagnosis of the oral component of SS and the presence of Abs; to investi- gate if the presence of Abs is predictive of a positive LSGB. Patients and methods. Retrospective study of clinical records between April 1992 and February 1999. The patients included fulfilled the following inclusion criteria: 1) have a suspected clinical diagnosis of primary SS or SS associated with other connective tissue disease (CTD) 2) have been submitted to LSGB that provided an adequate specimen for histologic examination 3) have at least one determination of rheumatoid factors, ANA, antiSSA and antiSSB. The patients included were 173 (166 F; 7 M); the mean age was 53.3 years (range 17-80; SD 12.0). The suspected clinical diagnosis prior to the biopsies were primary SS in 151 patients and SS associated with other CTD in 22 patients. The LSGB were obtained by punch or incisional techniques until December 1995 and after that by Daniels' technique (1). The histologic criteria for diagnosing SS were the presence of a focus score >1 per 4 mm 2 area of gland. The pathologist did not know the serological profile of each patient. We used the chi-square statistic for analysis of data.