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Biomedical subjects

J D Cañete

Publications and source records attributed to J D Cañete.

At least 19 recordsLinked to original sources
PubMed2006

Prognostic factors of radiographic progression in early rheumatoid arthritis: a two year prospective study after a structured therapeutic strategy using DMARDs and very low doses of glucocorticoids.

The objective of the study was to analyze the prognostic factors of radiographic progression in a series of patients with early rheumatoid arthritis (RA) after 2 years of therapy with a structured algorithm using disease-modifying antirheumatic drugs (DMARDs) and very low doses of oral glucocorticoids. One hundred and five patients (81% female) with early RA (disease duration <2 years) treated with the same therapeutic protocol using gold salts and methotrexate in a step-up strategy, together with methylprednisolone (4 mg/day), were followed up for 2 years. The outcome variable was radiographic progression after 2 years of DMARD therapy using the modified Larsen method. Clinical, biological, immunogenetic, and radiographic data were analyzed at study entry and after 1 and 2 years of follow-up. Radiographic progression (increase of four or more units in the Larsen score) was observed in 32% of patients after 2 years of follow-up. The percentage of erosive disease increased from 18.3% at baseline to 28.9% at 12 months and 44.6% at 24 months, in spite of a significant improvement in disease activity. New erosions appeared in 33% of patients after 2 years. Several baseline parameters were associated with radiographic progression in the univariate analysis: shared epitope (SE) homozygozity, HLA-DRB*04 alleles, female gender, hemoglobin, erythrocyte sedimentation rate, and anticyclic citrullinated peptide antibodies (anti-CCP). In the multivariate analysis, female gender [odds ratio (OR) 5.5, 95% confidence interval (CI): 1.1-28.2, p = 0.04], DRB1*04 alleles (OR 3.1, 95% CI 1.1-9, p = 0.03) and, marginally, anti-CCP antibodies (OR 3.6, 95% CI 0.9-14.5, p = 0.06), were associated with progression. Female patients with both DRB1*04 alleles and anti-CCP antibodies showed the highest scores in radiographic progression. The presence, but not the titer, of anti-CCP antibodies predicted progression. The positive predictive value of the multivariate model for progression was only 53.9% whereas the negative predictive value was 80.3%. In a series of early RA patients treated with a structured algorithm using DMARDs and very low doses of glucocorticoids, radiographic progression was observed in one third of patients after 2 years. Female gender, DRB1*04 alleles (rather than the SE), and the presence of anti-CCP antibodies at baseline (independently of the titer) were the most important predictors of progression. The utility of these parameters in clinical practice is limited by their relatively low positive predictive value.

Antirheumatic Agents↗
PubMed2006

Synovial vascular patterns and angiogenic factors expression in synovial tissue and serum of patients with rheumatoid arthritis.

OBJECTIVE: To determine whether subgroups of rheumatoid arthritis (RA) patients classified according to their synovial vascular pattern have a different expression of angiogenic mediators or exhibit distinct clinical or biological characteristics. METHODS: Arthroscopies were performed in 27 patients with RA and synovial samples were obtained. Vascular morphology was classified in three patterns: straight (S), tortuous (T) and mixed (M). Immunostaining was performed with anti-vascular endothelial growth factor (anti-VEGF), anti-vascular endothelial growth factor receptor (VEGFR)-1, anti-VEGFR-2, anti-IL-8 and anti-TGF-beta, and measured by digital image analysis. Serum levels of VEGF, TGF-beta and IL-8, and clinical, radiographic and serological data were also analysed. RESULTS: Eleven (41%) patients had the S pattern, nine (33%) the M pattern and seven (26%) the T pattern. The S and M groups had a higher prevalence of rheumatoid factor positivity and erosive disease, and higher levels of markers of systemic inflammation compared with the T group. Synovial expression of VEGF was higher in the S and T groups compared with the M group, whereas TGF-beta was higher in the T compared with the S and M groups. Distinct synovial distribution of VEGF and TGF-beta between groups was also observed. CONCLUSIONS: This preliminary study suggests that RA patients with the S and M patterns share different clinical, biological and serological characteristics compared with those with the T pattern, which may constitute a group with less severe disease. Differences in the intensity and distribution of synovial expression of VEGF and TGF-beta observed between groups could have pathophysiological relevance. However, larger, prospective multicentre studies would be need to determine the clinical relevance of vascular patterns in RA.

Adult↗
PubMed2005

Effectiveness of reducing infliximab dose interval in non-responder patients with refractory spondyloarthropathies. An open extension of a multicentre study.

OBJECTIVE: To evaluate the therapeutic effectiveness of reducing the infliximab dose interval to 6 weeks in spondyloarthropathy patients not responding to 5 mg/kg every 8 weeks. METHODS: After 30 weeks of infliximab therapy, 25 patients were classified as responders [Bath Ankylosing Spondylitis Activity Index (BASDAI) <4 cm or ESR <30 mm/h and CRP <5 mg/l, n = 15; group A] or non-responders (patients who did not achieve the response established for group A; n = 10; group B). Responders continued on 5 mg/kg every 8 weeks and non-responders decreased the dose interval to 6 weeks. BASDAI, Bath Ankylosing Spondylitis Functional Index (BASFI), ESR, CRP and ankylosing spondylitis assessment (ASAS) criteria were used to assess response. RESULTS: At 62 weeks, 11 of 15 patients (73.3%, 95% confidence interval = 44.9-92.2%) from group A and three of 10 patients (30%, 95% confidence interval = 6.7-65.2) from group B were responders (P = 0.049). Eighty per cent (eight of 10 patients from group A) and 22.2% (two of 9 patients from group B) achieved 50% BASDAI improvement (P = 0.023), and nine of 11 patients (81.8%) and four of 10 (40%) from groups A and B, respectively, reached ASAS20 at 62 weeks (P = 0.08). CONCLUSION: Patients on infliximab 5 mg/kg every 8 weeks with persistent disease activity may benefit from reducing the dose interval to 6 weeks.

Adult↗
PubMed2005

p53 expression in rheumatoid and psoriatic arthritis synovial tissue and association with joint damage.

BACKGROUND: Overexpression and functional mutations of p53 have been found in the synovial tissue (ST) of patients with rheumatoid arthritis (RA), but their clinical significance remains unclear. OBJECTIVE: To analyse p53 expression in the ST of patients with RA and psoriatic arthritis (PsA) and its association with joint damage. METHODS: Synovial biopsy specimens were obtained by arthroscopy in 45 patients (27 RA, 18 PsA). Radiographs of hands, feet, and the joint undergoing arthroscopy were obtained to evaluate the presence of erosive disease. Synovial cell populations were analysed using CD4, CD8, CD138, CD20, and CD68 monoclonal antibodies (mAbs). The p53 protein was determined by immunohistology using DO7 mAb in 34 patients (18 RA, 16 PsA). In 11 patients with early RA, the association between p53 and 1 year progression of radiographic damage was analysed using the Larsen-Scott method. RESULTS: The p53 protein was detected in 16/18 (89%) patients with RA and in 9/16 (56%) patients with PsA, but its expression in RA was significantly higher than in PsA. In RA, p53 expression was significantly associated with erosive disease, and its scores were higher in patients with radiological progression. CD68 expression was also associated with erosions and radiological progression in RA. No association was found between either p53 or CD68 and erosive disease in PsA. CONCLUSIONS: These results suggest that p53 ST overexpression and association with joint damage is characteristic of RA rather than PsA, and that p53 ST expression might be a prognostic marker of joint damage in RA.

Adult↗
PubMed2001

The clinical significance of amyloid fat deposits in rheumatoid arthritis: a systematic long-term followup study using abdominal fat aspiration.

OBJECTIVE: To analyze the prevalence of subclinical amyloid fat deposits in patients with rheumatoid arthritis (RA) and to evaluate its clinical significance. METHODS: A cohort of 313 adult RA patients were included in this prospective observational study. Systematic abdominal subcutaneous fat aspiration (ASFA) was performed on all patients at study entry. The prevalence of visceral amyloidosis at study entry and at the end of followup was analyzed for patients with a positive ASFA test result. Followup ranged from 1 to 14 years (mean +/- SD 6.7 +/- 4.1 years). Patients with clinical and subclinical amyloidosis were compared with regard to clinical characteristics and the degree of amyloid deposits in abdominal fat. RESULTS: The first ASFA test found amyloid in the abdominal fat of 51 patients (16.3%), and subsequent ASFA tests found amyloid in the abdominal fat of 10 additional patients. At the time of the ASFA test, amyloidosis was subclinical in 45 of these 61 patients, 41 of whom were followed up. During followup, 11 of these 41 patients developed renal involvement, 5 due to amyloid nephropathy. Thus, amyloidosis remained subclinical in at least 30 of 41 patients (73%) throughout followup. Marked amyloid fat deposits were found more frequently in patients with clinical amyloidosis than in those whose amyloidosis remained subclinical at the end of followup (57% versus 22%; P = 0.04). CONCLUSION: Amyloid fat deposits are not uncommon in adult RA. In the majority of patients, the deposits do not indicate clinically evident organic dysfunction, even after several years of followup. Patients with more extensive fat deposits may have a higher risk of developing clinical amyloidosis.

Abdomen↗
PubMed2000

Differential Th1/Th2 cytokine patterns in chronic arthritis: interferon gamma is highly expressed in synovium of rheumatoid arthritis compared with seronegative spondyloarthropathies.

OBJECTIVE: To investigate possible differences in Th1 and Th2 cytokine mRNA expression in the synovial tissue (ST) of patients with rheumatoid arthritis (RA) and seronegative spondyloarthropathies (SpA) with diagnostic and/or pathogenic interest. METHODS: Eleven RA patients and 14 SpA patients (10 with undifferentiated spondyloarthropathy (USpA), two with ankylosing spondylitis (AS) and two with psoriatic arthritis (PsA)) were included. Th1 (interferon gamma, interleukin 2) and Th2 (interleukin 4, interleukin 5 and interleukin 10) cytokine mRNA levels from arthritic knee ST were quantified by using an optimised polymerase chain reaction method with a computerised analysis system. Protein levels of proinflammatory cytokines (interleukin 1, tumour necrosis factor alpha and interleukin 6) in synovial fluid were quantified with a specific ELISA test. RESULTS: Th1 cytokines were detected in all of RA ST samples in contrast with 58% (interferon gamma) and 71% (interleukin 2) of SpA samples. Th2 cytokines were expressed in 90% of RA ST samples, but the findings in SpA were interleukin 10 in 90%, interleukin 4 in 60% and interleukin 5 in 40% of ST samples. However, when the mRNA levels of each cytokine were quantified and corrected for T cell mRNA levels, only interferon gamma levels were significantly higher in RA than in SpA (p<0.003). Thus, the Th1/Th2 cytokine ratio in RA was fivefold that of SpA. Synovial fluid interleukin 1beta concentrations were higher in RA than in SpA (p<0. 05); there were also higher synovial fluid levels of tumour necrosis factor alpha in RA than in SpA, but without statistical significance. CONCLUSION: This study has detected both Th1 and Th2 cytokine gene expression in ST from RA and SpA patients. Synovium interferon gamma mRNA levels and SF interleukin 1beta protein levels were significantly higher in RA than in SpA, so reflecting the known proinflammatory activity of interferon gamma through macrophage activation. Thus, the Th1 (interferon gamma)/Th2 (interleukin 4) ratio is significantly higher in RA than in SpA ST. These data confirm previous studies on ST Th1/Th2 balance in RA and extend previous work in comparing ST RA with subgroups of SpA distinct of ReA.

Adult↗
PubMed1999

Idiopathic hypoparathyroidism associated with adult rheumatoid arthritis.

A 48-year-old female patient with adult onset idiopathic hypoparathyroidism diagnosed at the age of 28 years developed a typical seropositive rheumatoid arthritis (RA) at 46 years of age after several years of evolution of a palindromic rheumatism. Only one case of an association between idiopathic hypoparathyroidism and RA has been described in the medical literature. Autoimmunity seems to play a pivotal role in the aetiopathogenesis of both diseases, and could explain the nature of this association; nevertheless, a chance association could not be excluded.

Absorptiometry, Photon↗
PubMed1997

Comparative cytokine gene expression in synovial tissue of early rheumatoid arthritis and seronegative spondyloarthropathies.

Interleukin 1-beta (IL-1 beta), IL-2, IL-4, IL-5, IL-6, IL-8, tumour necrosis factor-alpha (TNF-alpha), transforming growth factor-beta (TGF-beta) and granulocyte-macrophage colony-stimulating factor (GM-CSF) gene expression was determined in knee synovium of 16 patients with rheumatoid arthritis (RA) and 16 patients with seronegative spondyloarthropathies (SSP), by using polymerase chain reaction (PCR) amplification. The pattern of cytokines observed in RA synovium is of the macrophage-fibroblast type, with the highest expression of IL-1 beta and TGF-beta. GM-CSF and IL-2 bands were visualized in a minority of patients. Neither IL-4 nor IL-5 could be detected. No significant differences were observed in the cytokine profile between patients with early (< 12 months) and more advanced disease. No differences were observed according to gender, age, rheumatoid factor status and the duration of knee synovitis. The pattern of cytokines in the synovium of SSP patients is similar to that observed in RA patients and does not change in relation to disease duration. IL-2 was the only T-cell cytokine observed. These data provide evidence that the macrophage-fibroblast cells have an important role in early and more advanced rheumatoid synovitis, and show that this is also true for SSP peripheral synovitis.

Adult↗
PubMed1996

Reduced serum creatine kinase activity in inflammatory rheumatic diseases.

OBJECTIVE: To determine if serum CK activity is reduced in inflammatory rheumatic diseases and to evaluate whether this phenomenon is linked to disease activity or steroid therapy. METHODS: Serum CK activity was measured in patients with systemic lupus erythematosus (SLE, n = 52), rheumatoid arthritis (RA, n = 80), ankylosing spondylitis (AS, n = 82), spondyloarthropathies other than AS (SpA, n = 22), and a miscellaneous group (MI, n = 27), and in 103 control patients with noninflammatory arthropathies (NIA). Laboratory variables of inflammatory activity such as ESR, CRP, platelet count, and hemoglobin (and anti-DNA antibodies and complement levels in SLE) were measured at the same time. Daily dose of steroids was also evaluated. RESULTS: Serum CK activity was significantly reduced in SLE (mean +/- SD: 49 +/- 41 IU/l), RA (68 +/- 41 IU/l), SpA (88 +/- 53 IU/l), and MI (75 +/- 32 IU/l) compared to controls (111 +/- 38 IU/l) (p = 0.002 for SpA and p < 0.001 for the other groups). No differences in CK values were observed between AS and controls, although AS patients with peripheral arthritis had lower serum CK activity than those without (80 +/- 32 vs 121 +/- 62 IU/l, respectively, p < 0.05. ESR, CRP, and platelets correlated inversely with CK values in RA, AS, and MI. In the SpA group only ESR correlated inversely with CK. In SLE, a positive correlation was found between CK values and CH50 and a negative one with anti-DNA levels. Patients taking steroids had significantly lower CK activity than those without corticotherapy. However, multivariate analysis showed that only inflammatory activity and no steroids had an effect in reducing CK activity. CONCLUSION: Serum CK activity is significantly reduced in several inflammatory rheumatic diseases. Inflammatory activity seems to play the major role in this phenomenon.

Adult↗
PubMed1992

Non-association between 9.2 KB PvuII RFLP and seronegative spondyloarthropathies in Spain.

Several studies of DNA restriction fragment length polymorphism (RFLP) in ankylosing spondylitis (AS) have been carried out. The association between a recently identified class I HLA 9.2 kb PvuII RFLP and AS remain controversial. In order to evaluate this possible association in an Euro-Caucasian population, the genomic DNA of 42 AS patients and 18 patients with Reiter's syndrome (RS) and 42 healthy controls was analysed. Non-association between 9.2 kb PvuII RFLP and AS or RS was observed. As described previously, a strong association between this fragment and HLA-A3 and/or HLA-A9 antigens was demonstrated. A study of two families showed that this RFLP segregates with HLA-A3 and/or HLA-A9 and independently of the HLA-B27. Our findings support the view that the 9.2 kb PvuII fragment is not universally associated with AS.

Arthritis, Reactive↗
PubMed1989

Giant-cell arteritis presenting with ipsilateral hemiplegia and lateral medullary syndrome.

We describe the clinical and anatomopathological findings in an 85-year-old male presenting with a lateral medullary syndrome and ipsilateral hemiplegia (Opalski's syndrome) due to giant-cell arteritis of the vertebral artery. Other common associated symptoms of the disease were absent, and the erythrocyte sedimentation rate was only of 30 mm/h. This case emphasizes that limited intracranial giant-cell arteritis may present rarely as a stroke.

Aged↗
PubMed1988

Immunoglobulin A in the skin of patients with ankylosing spondylitis.

Cutaneous immunofluorescence studies were carried out in 21 patients with ankylosing spondylitis (AS) and the results compared with those for 18 healthy subjects. The most prominent finding was the presence of IgA in dermal vessels of patients with AS (71% compared with 17% of the control group). IgG and IgM cutaneous deposits were also observed in patients with AS, but these results did not differ from those of the control group. A renal biopsy was performed in three of the patients presenting with unexplained microscopic haematuria. One of them had an IgA nephropathy, but no correlation was found between kidney and skin deposits of IgA. These findings suggest that IgA cutaneous deposits in AS are not a marker of IgA nephropathy but stress the role of immunoglobulin A in the pathogenesis of this disease.

Adult↗
PubMed1988

Spinal cord compression by a unifocal eosinophilic granuloma: a case report of an adult with unusual roentgenological features.

We describe an unusual case of unifocal eosinophilic granuloma of the spine in a 38-year-old woman who presented with spinal cord compression. After 2 years of back pain, x-ray films of the spine were normal, but computed tomography and magnetic resonance imaging demonstrated a lytic lesion of the 1st lumbar vertebral body with cephalic extension in the epidural space. The lesion was later confirmed at operation to be an eosinophilic granuloma spreading into the surrounding tissues.

Adult↗