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Biomedical subjects

R Burgos-Vargas

Publications and source records attributed to R Burgos-Vargas.

At least 19 recordsLinked to original sources

IgG antibodies to enterobacteria 60 kDa heat shock proteins in the sera of HLA-B27 positive ankylosing spondylitis patients.

OBJECTIVE: To study the association of HLA-B27 and the IgG response to the 60 kDa HSPs of Klebsiella pneumoniae, Yersinia enterocolitica, Shigella flexneri, Escherichia coli and Salmonella typhi. METHODS: IgG against the 60 kDa HSPs of enterobacteria was determined by ELISA in the sera from 49 HLA-B27+ ankylosing spondylitis (AS) patients; 41 HLA-B27+ healthy relatives of AS patients and 101 HLA-B27-unrelated healthy individuals. RESULTS: HLA-B27+ patients and healthy individuals, showed significantly higher IgG antibody levels to the Klebsiella, Yersinia and Salmonella HSPs than HLA-B27- healthy controls. B27+ patients had a significantly higher response to E. coli HSP than the two other groups. IgG response anti-Shigella HSP was similar in the three groups. CONCLUSIONS: There is a relationship between HLA-B27 and the response to HSPs 60 from Klebsiella, Yersinia, Escherichia and Salmonella, that may be important in the initiation of AS.

Antibodies, Bacterial↗

Heat shock protein 70 gene polymorphisms in Mexican patients with spondyloarthropathies.

OBJECTIVE: To investigate the role of HSP70 genes as contributors to genetic susceptibility of the spondyloarthropathies (SpA) in the Mexican population. METHODS: The study included 150 patients with SpA (undifferentiated spondyloarthropathy (uSpA) 68, ankylosing spondylitis (AS) 60, and reactive arthritis 22) and 158 healthy controls. HSP70-1, HSP70-2 and HSP70-hom genotypes were analysed by the polymerase chain reaction-restriction fragment length polymorphism technique. Statistical methods included the Mantel-Haenzel, chi(2), Fisher's exact test, and Woolf's method for odds ratio (OR). RESULTS: HSP70-2 B/B genotype frequency was increased in the whole group of patients with SpA (pC<0.05, OR=4.3), as well as in the different clinical subgroups (pC<0.05, OR=4.2 for AS; pC<0.05, OR=4.4 for uSpA; and pC<0.05, OR=4.1 for ReA). This frequency remained significantly increased when the patients with B27 negative SpA were analysed. On the other hand, HSP70-hom locus analysis showed significantly increased frequency of A allele in the whole group of SpA (pC<0.05, OR=3.4), as well as in the groups with AS (pC<0.05, OR=5.6) and with uSpA (pC<0.05, OR=3.1), when compared with healthy controls. In this case, also, the genotype A/A was increased in the whole group of SpA (pC<0.05, OR=4.5), as well as in patients with AS (pC<0.05, OR=6.4) and with uSpA (pC<0.05, OR=3.7). When the patients with B27 negative SpA were analysed the frequencies of HSP70-hom A allele and A/A genotype remained significantly increased in the whole group of SpA (pC<0.05, OR=3.2 for the A allele and pC<0.05, OR=4.2 for the A/A genotype) and in the uSpA subgroup (pC<0.05, OR=3.8 for the A allele and pC<0.05, OR=4.3 for the A/A genotype). CONCLUSION: In addition to the association of SpA with HLA-B27, there is a significant association of HSP70-2 and HSP70-hom alleles with SpA in Mexicans. This association seems to be independent of the susceptibility conferred by HLA-B27 in the group of patients with uSpA.

Adult↗

Development of a radiographic index to assess the tarsal involvement in patients with spondyloarthropathies.

OBJECTIVE: To develop and test an index to evaluate the radiographic changes that occur in the tarsus and adjacent areas of the foot in patients with spondyloarthropathies (SpA). METHODS: The spondyloarthropathy tarsal radiographic index (SpA-TRI) was developed in three consecutive steps: (a) detection of descriptors after reviewing 70 radiographic files; (b) descriptor gradation and subsequent modifications performed by a consensus committee, and (c) interobserver variability assessed by three blinded and independent observers on 272 radiographs: anteroposterior 118, lateral 90, oblique 64 from 121 patients with SpA, and intraobserver variability on 75 radiographs from 25 patients with SpA. Statistical analysis included percentage of agreement and kappa test. SpA-TRI score ranges from 0 to 4 (0=normal; 1=osteopenia or suspicious findings; 2=definite joint space narrowing, bony erosion(s), periosteal whiskering, or enthesophyte(s) in the plantar fascia or Achilleal tendon attachments; 3=para-articular enthesophyte(s); 4=bony ankylosis (joint space fusion or complete bridging)). RESULTS: Complete agreement for every evaluation was >40%, and discordance >1 grade was <15%. The kappa scores among the three observers were acceptable for all the single projections: oblique (0.52, 0.36, 0.35), lateral (0.50, 0.42, 0.56), and anteroposterior (0.40, 0.41, 0.21) views. The combination of lateral and oblique views achieved the highest concordance rates (0.72, 0.33, 0.66), surpassing that of the three projections altogether (0.34, 0.58, 0.37). In every case the concordance was comparable with that of sacroiliac joints (0.47, 0.41, 0.34); intraobserver concordance showed a similar trend. CONCLUSION: The SpA-TRI is an index that includes the most prominent features of tarsal disease and adjacent areas of the foot in SpA and grades them accordingly, it has an adequate reproducibility, and is suitable for use with two or more projections, preferably the combination of oblique and lateral.

Adolescent↗

Effect of HLA-B and HLA-DR genes on susceptibility to and severity of spondyloarthropathies in Mexican patients.

OBJECTIVE: To investigate the role of HLA-B and HLA-DR genes as contributors to genetic susceptibility and clinical expression of the spondyloarthropathies (SpA) in the Mexican population. METHODS: The study included 172 patients with SpA (undifferentiated SpA 83, ankylosing spondylitis (AS) 64, and reactive arthritis 25) and 99 healthy controls. The HLA-B and HLA-DR alleles were detected by the polymerase chain reaction with sequence-specific primers technique. Patient assessment included demographic data, diagnostic categories, and disease patterns. Statistical methods included the Mantel-Haenzel chi(2) test, Fisher's exact test, and Woolf method for odds ratio (OR). Differences of continuous variables between HLA allele groups were calculated by Student's t test. RESULTS: Increased frequencies of HLA-B27 (pCh10(-3), OR=28.7), HLA-DR1 (pC=0.045, OR=2.77), and HLA-B15 (p=0.034, pC=NS, OR=2.04) alleles in the whole group were found. HLA-B27 strength of association (OR) was 41.4 in AS; 20.9 in undifferentiated SpA; 27.2 in reactive arthritis. HLA-DR1 and HLA-B15 were increased in undifferentiated SpA (pC=0.045, OR=2.98 and p=0.004, pC=NS, OR=2.75). By analysing 58 HLA-B27 negative patients it was found that HLA-B15 and HLA-DR1 associations with SpA were independent of HLA-B27; increased frequencies of HLA-B15 were found in the whole SpA group and in patients with undifferentiated SpA (pC=0.03, OR=3.09 and pCh0.01, OR=3.77) and of HLA-DR1 in the latter (p=0.04, pC=NS, OR=3.15). HLA-B27 positive patients were younger than HLA-B27 negative patients at onset (p=0.03), but HLA-DR1 positive patients were older than HLA-DR1 negative patients (p=0.03). Bath indices for disease activity and functioning were higher in HLA-B27 positive patients (p=0.006 and p=0.004 v HLA-B27 negative patients). In contrast, neither HLA-DR1 nor HLA-B15 influenced these indices. CONCLUSION: Apart from HLA-B27, there is a significant association of HLA-DR1 and HLA-B15 with SpA in Mexicans which is independent of B27. HLA-B27 is associated with younger age at onset and increased disease severity and HLA-DR1 with older age at onset. The strength of HLA-B15, HLA-B27, and HLA-DR1 associations varied in different forms of SpA.

Adult↗

Juvenile onset spondyloarthropathies: therapeutic aspects.

Juvenile onset spondyloarthropathy (SpA) is a term that refers to a group of human leucocyte antigen (HLA)-B27 associated inflammatory disorders affecting children under the age of 16 years, producing a continuum of clinical symptoms through adulthood. This disease is characterised by enthesopathy and arthropathy affecting the joints of the lower extremities and seronegativity for IgM rheumatoid factor and antinuclear antibodies. Children usually present with undifferentiated SpA and progress to differentiated forms over time. Except for the prevalence of some clinical features at onset, the pathogenic and clinical aspects of juvenile onset SpAs resemble those of the adult disease. Thus application of the same or similar therapeutic measures for both juvenile and adult onset SpAs seems logical. Current treatments for juvenile onset SpA provide symptomatic improvement, but do not alter disease progression. The increased expression of tumour necrosis factor alpha (TNFalpha) in synovial tissue of patients with adult and juvenile onset SpA and its correlation with infiltration of inflammatory mediators into the synovia suggest a significant pathogenic role of this cytokine. Clinical trials of anti-TNFalpha antibody (infliximab) therapy in patients with adult onset SpA have demonstrated significant clinical improvement in inflammatory pain, function, disease activity, and quality of life in correlation with histological and immunohistochemical evidence of modulation of synovial inflammatory processes. These promising findings suggest that anti-TNFalpha therapy may confer similar benefits in patients with juvenile onset SpA.

Adolescent↗

Bacterial DNA in synovial fluid cells of patients with juvenile onset spondyloarthropathies.

OBJECTIVE: To identify bacterial DNA in synovial fluid cells of patients with active juvenile onset spondyloarthropathy (SpA). METHODS: The main group of study constituted 22 patients with juvenile onset SpA. In addition, five patients with adult onset SpA and nine with rheumatoid arthritis (RA) were studied. Polymerase chain reaction (PCR) with either genus- or species-specific primers was performed on synovial fluid cells to detect DNA sequences of Chlamydia trachomatis, Yersinia enterocolitica, Salmonella sp., Shigella sp., Campylobacter sp. and Mycobacterium tuberculosis. The presence of antibacterial antibodies in sera and synovial fluid was also determined by enzyme-linked immunoassay. RESULTS: The synovial fluid of nine patients with juvenile onset SpA, three with adult onset SpA and one with RA contained bacterial DNA. Five juvenile onset SpA samples had DNA of one single bacterium; two juvenile onset SpA and three adult onset SpA had DNA of two bacteria and two juvenile onset SpA had DNA of three bacteria. Overall, Salmonella sp. DNA was detected in seven synovial fluid samples, Shigella sp., Campylobacter sp. and M. tuberculosis were found in four samples each, and C. trachomatis was found in two. The bacterial DNA findings correlated with neither diagnosis nor disease duration. One RA synovial fluid had DNA of Campylobacter sp. Neither serum nor synovial fluid antibacterial antibodies correlated with DNA findings or clinical diagnosis. CONCLUSION: In this study, single and several combinations of bacterial DNA were identified in the synovial fluid of patients with long-term undifferentiated and definite juvenile onset SpA and adult onset SpA. Of relevance is that bacterial DNA corresponds to bacteria producing endemic disease in our population.

Adolescent↗

Relation between adverse events associated with allopurinol and renal function in patients with gout.

BACKGROUND: Because serious adverse reactions to allopurinol have been related to a reduce creatinine clearance rate and prolonged half life of oxypurinol, it has been recommended that the dose should be adjusted according to the rate of creatinine clearance. However, in some patients with gout the dose is not sufficient to reduce serum levels of uric acid (< or =390 micromol/l) and to halt disease progression. OBJECTIVE: To determine the prevalence of adverse reactions attributable to allopurinol in patients with primary gout according to dose and creatinine clearance rate. METHODS: Data on 120 patients with gout receiving allopurinol, in whom the starting dose was adjusted according to creatinine clearance rate and later increased in some patients to control the disease, were retrospectively reviewed. Two groups were compared: group A, 52 patients receiving creatinine clearance adjusted maintenance doses of allopurinol and group B, 68 patients receiving non-adjusted higher maintenance doses of allopurinol. RESULTS: During follow up 57% required higher allopurinol doses than those recommended according to their creatinine clearance rate. Only five (4%) of 120 consecutive patients developed allopurinol related adverse reactions: four minor skin reactions and one allopurinol hypersensitivity syndrome (AHS). Three of these (including the case of AHS) occurred in group A and two in group B (p=NS). The duration of allopurinol treatment was the same in both groups (group A: 2.3 (3.3) years; group B: 3.7 (4.8) years). No patient in group A, but 44% in group B had a creatinine clearance rate of <50 ml/min. None of the patients received concomitant diuretics, ampicillin, or azathioprine. CONCLUSIONS: No increase was seen in the prevalence of adverse reactions to allopurinol in patients who received higher allopurinol maintenance doses than those recommended according to creatinine clearance rate.

Adult↗

Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis. VIGOR Study Group.

BACKGROUND: Each year, clinical upper gastrointestinal events occur in 2 to 4 percent of patients who are taking nonselective nonsteroidal antiinflammatory drugs (NSAIDs). We assessed whether rofecoxib, a selective inhibitor of cyclooxygenase-2, would be associated with a lower incidence of clinically important upper gastrointestinal events than is the nonselective NSAID naproxen among patients with rheumatoid arthritis. METHODS: We randomly assigned 8076 patients who were at least 50 years of age (or at least 40 years of age and receiving long-term glucocorticoid therapy) and who had rheumatoid arthritis to receive either 50 mg of rofecoxib daily or 500 mg of naproxen twice daily. The primary end point was confirmed clinical upper gastrointestinal events (gastroduodenal perforation or obstruction, upper gastrointestinal bleeding, and symptomatic gastroduodenal ulcers). RESULTS: Rofecoxib and naproxen had similar efficacy against rheumatoid arthritis. During a median follow-up of 9.0 months, 2.1 confirmed gastrointestinal events per 100 patient-years occurred with rofecoxib, as compared with 4.5 per 100 patient-years with naproxen (relative risk, 0.5; 95 percent confidence interval, 0.3 to 0.6; P<0.001). The respective rates of complicated confirmed events (perforation, obstruction, and severe upper gastrointestinal bleeding) were 0.6 per 100 patient-years and 1.4 per 100 patient-years (relative risk, 0.4; 95 percent confidence interval, 0.2 to 0.8; P=0.005). The incidence of myocardial infarction was lower among patients in the naproxen group than among those in the rofecoxib group (0.1 percent vs. 0.4 percent; relative risk, 0.2; 95 percent confidence interval, 0.1 to 0.7); the overall mortality rate and the rate of death from cardiovascular causes were similar in the two groups. CONCLUSIONS: In patients with rheumatoid arthritis, treatment with rofecoxib, a selective inhibitor of cyclooxygenase-2, is associated with significantly fewer clinically important upper gastrointestinal events than treatment with naproxen, a nonselective inhibitor.

Adult↗

Recognition of B cells epitopes of the Klebsiella pneumoniae GroEL-like protein by HLA-B27 positive subjects.

The presence of antibodies against antigens of K. pneumoniae in HLA-B27 positive patients with ankylosing spondylitis (AS), has been well documented. We have previously reported that sera from HLA-B27 positive subjects react with the K. pneumoniae GroEL-like protein (HSP60Kp) and have higher titers than HLA-B27 negative individuals. We cloned the gene that codes for this protein, determined hydrophilic regions by computer analysis of the predicted amino acid sequence and found that residues 389-397, 360-368 and 282-290, were possible B cell epitopes. To test this prediction, and to determine if the HLA-B27 positive and negative AS patients recognize the same or different epitopes, we truncated the hsp60Kp gene, from the 3; terminal nucleotide, to obtain fragments having or not the predicted epitopes. Four polypeptides of 40, 37, 30 and 18 kDa were obtained and analysed, by ELISA and inhibition of ELISA, for their reactivity with IgG antibodies from three high responders HLA-B27 positive AS patients and three HLA-B27 negative subjects who recognized the rHSP60Kp. Sera from both HLA-B27 positive and negative subjects reacted equally well with rHSP60Kp or with the 40 and 37 kDa peptides, which do not have residues 389-397 and 360-368, respectively, but reactivity was lost with the 30 kDa peptide, which also lacks residues 282-290. Contrary to what we expected, antibodies from HLA-B27 negative and positive individuals recognized the same epitope of the HSP60Kp. Our results indicate that the important epitope for B cells could be the 282-290 region and that the contribution of the two other predicted regions is minimal. We also conclude that the differences in response to the HSP60Kp in HLA-B27 positive AS patients and HLA-B27 negative individuals is not qualitative, but only quantitative.

Animals↗

Update on functional assessment tools.

In recent years, there has been a tremendous growth in the development of measurement instruments that evaluate health status, functional status, disability, and quality of life in adults with rheumatic diseases. In the past decade, similar measures have been developed for application in children with rheumatic diseases. These include the Childhood Arthritis Impact Measurement Scales (CHAIMS), the Childhood Health Assessment Questionnaire (CHAQ), the Juvenile Arthritis Functional Assessment Report (JAFAR), the Juvenile Arthritis Self-report Index (JASI), the Juvenile Arthritis Quality of Life Questionnaire (JAQQ), and the Childhood Arthritis Health Profile (CAHP). The latter 2 instruments assess health related quality of life (HRQOL) and they are discussed here. The need to adapt this kind of instrument for use in an international climate creates an interesting dilemma and this is discussed.

Arthritis, Juvenile↗

Cellular immune response to Klebsiella pneumoniae antigens in patients with HLA-B27+ ankylosing spondylitis.

OBJECTIVE: To study the reactivity of peripheral blood mononuclear cells (PBMC) of patients with ankylosing spondylitis (AS) and rheumatoid arthritis (RA) and healthy controls to Klebsiella pneumoniae antigens and to the GroEL-like proteins from K. pneumoniae (HSP60Kp) and Mycobacterium leprae recombinant heat shock protein 65 (rHSP65Ml). METHODS: PBMC of 13 patients with AS and 9 with RA and 10 controls were stimulated in vitro by heat shock induced K. pneumoniae antigens in a cell blot assay, by insolubilized HSP60Kp, by cytosolic proteins (CP) from K. pneumoniae cultivated at 37 degrees C or 45 degrees C, by soluble HSP60Kp, or by rHSP65Ml. RESULTS: In the cell blot assay 7/13 AS and 3/9 RA patients responded to fraction 4, which contains mainly HSP60Kp, and no controls responded (AS vs. controls: p = 0.007). The response to the insolubilized HSP60Kp was positive in 6/13 AS patients but negative in RA patients and controls (p = 0.004). The response to CP45 degrees C was positive in 7/13 AS, in 2/9 RA, and no controls (AS vs controls: p<0.015). Response to the soluble HSP60Kp was found in 7/13 AS and 5/9 RA patients, but no controls (AS vs. controls: p = 0.0075). Response to rHSP65Ml was positive in 3/13 AS, 7/9 RA patients, and 1/10 controls (AS vs RA: p = 0.027; RA vs. controls: p = 0.005; AS vs. controls: nonsignificant). CONCLUSION: In PBMC of the majority of patients with AS and in some with RA, but not in healthy controls, there are cells that proliferate in the presence of HSP60 of K. pneumoniae.

Adolescent↗

Comparison of two schedules for administering oral low-dose methotrexate (weekly versus every-other-week) in patients with rheumatoid arthritis in remission: a twenty-four week, single blind, randomized study.

OBJECTIVE: To compare the efficacy of 2 low-dose oral methotrexate (MTX) schedules in maintaining remission in patients with rheumatoid arthritis (RA). METHODS: Patients with RA were included if they were receiving treatment with weekly MTX for at least 9 months and the RA was in remission (defined by American College of Rheumatology [ACR] criteria) for at least 6 months. Patients were stratified by treatment and randomly assigned to weekly or every-other-weekly (EOW; reducing their monthly dose by half) treatment with MTX. Patients were evaluated by a rheumatologist (blinded to the treatment schedule) at baseline and at 6, 12, and 24 weeks. The evaluations included joint counts, Ritchie Articular Index, Health Assessment Questionnaire Disability Index, physician's and patient's global health assessments, visual analog scale for pain, and incidence of adverse effects. Laboratory evaluations were done at baseline and at week 24. RESULTS: Fifty-one patients were included (26 taking weekly MTX, 25 taking EOW MTX). Baseline comparisons showed no differences between the groups. The mean duration of RA was <3 years in both groups, and they had been started on weekly MTX treatment early after diagnosis. After 24 weeks, >90% of the patients in both groups continued in remission. Evaluations of disease activity at 6 and 12 weeks showed no between-group differences. EOW MTX patients who experienced relapse were switched back to weekly MTX, and after a few weeks, their RA was again controlled. The incidence of adverse effects was slightly higher in the weekly MTX group, although the difference did not reach statistical significance. The observed laboratory values were very similar for both groups, except for the serum aspartate aminotransferase and alanine aminotransferase levels, which decreased in the EOW MTX group and were statistically significant at week 24 (P = 0.04 and P = 0.006, respectively). CONCLUSION: EOW MTX represents a valid therapeutic alternative for a specific subgroup of RA patients, as outlined by the ACR remission criteria. Patients with a short disease duration who were treated early after disease onset with weekly MTX and who achieve sustained remission have a higher probability of success with the EOW MTX schedule.

Administration, Oral↗

A proposal for the classification of patients for clinical and experimental studies on reactive arthritis.

OBJECTIVE: To propose classification criteria for patients entering clinical and basic studies on reactive arthritis (ReA). METHODS: From a MEDLINE search of articles published between 1980 and 1996, we identified reports on HLA-B27 related ReA and Reiter's syndrome as study groups and analyzed the items that constituted the diagnostic, classification, and inclusion (or entry) criteria of patients. We developed disease categories that constituted our classification proposal. RESULTS: We reviewed 175 articles containing 110 study groups of patients with ReA and 94 with Reiter's syndrome. Most articles (89.7%) relied on arthritis for diagnosis, but only 48.0% relied on infection. Only 22.5% of articles used published criteria for diagnosis. Articles including a bacterial name to further describe a group of patients with ReA relied on cultures at the site of infection, serum antibodies, or both to confirm the diagnosis. There were inter/intra-group variations and overlapping of diagnostic criteria, at least 32 different terms referring to ReA or Reiter's syndrome, and 6 patterns of disease. According to these data, we propose 3 categories of disease for patients entering clinical and basic studies on ReA: probable ReA (2 subgroups); definite ReA triggered by bacteria (2 subgroups); and bacterial-associated undifferentiated oligoarthritis or spondyloarthropathy. CONCLUSION: This proposal provides a rationale for reducing the heterogeneity found in criteria for including patients with ReA in research and to facilitate scientific communication. In contrast to diagnostic criteria, this proposal does not restrict the study population to a minority of patients, but allows the investigator to include several forms of disease and to analyze results according to different categories.

Arthritis, Reactive↗

Intradermal tophi in gout: a case-control study.

OBJECTIVE: To describe the characteristics of intradermal tophi in patients with gout and search for factors associated with their development. METHODS: This is a case-control study of patients with gout: cases (Group A, n = 21) had intradermal (not subcutaneous) plaques of monosodium urate (MSU) crystals located in sites distant to articular or paraarticular structures, and controls (Group B, n = 42) had gout but no intradermal tophi. Both Group A and Group B were paired by sex, age (+/-5 years), and duration of the disease (+/-3 years). Analysis included serum and urinary uric acid levels at first visit, radiographic stage of gout, the presence of associated diseases, and previous therapy, specifically, chronic glucocorticoid and diuretic usage. RESULTS: Intradermal tophi were located in the legs, forearms, buttocks, thighs, arms, and abdominal wall. Patients in Group A had a greater number of nonintradermal tophi in common sites (11.9+/-12.5 vs. 4.2+/-7.9, mean +/- SD; p = 0.018), decreased glomerular filtration rate (46.74+/-25.11 vs. 70.87+/-30.18 ml/min; p = 0.042), advanced radiographic changes (57.2 vs. 7.1%; p = 0.0001), and longterm glucocorticoid self-medication (76 vs. 36%; p = 0.006). We found no differences in other associated diseases between groups. CONCLUSION: Intradermal tophi were commonly found in the legs and forearms, and less frequently in the buttocks, thighs, and abdominal wall of gouty patients, and were associated with longterm self-prescribed glucocorticoids and chronic renal failure. The occurrence of intradermal tophi in these patients appeared to correlate with advanced disease.

Adult↗