Biomedical subjects

C A Brand

Publications and source records attributed to C A Brand.

9 recordsLinked to original sources

PubMed2005

Clinical, laboratory and genetic markers associated with erosions and remission in patients with early inflammatory arthritis: a prospective cohort study.

We investigated the relationship between clinical, laboratory and genetic markers and outcome measures in 159 patients with recent onset of inflammatory arthritis (IA). The majority of patients were managed in community-based rheumatology practice. Median duration of arthritis at baseline was 3 months with median follow-up of 4.0 years (range 0-10). Markers of disease activity and 1987 ACR criteria for rheumatoid arthritis (RA) were estimated every 6 months for the first 2 years and annually thereafter. Presence of shared epitopes (SE) was established by PCR-based method. Main outcome variables were attainment of remission and presence of erosions on X-rays of hands and feet at 3 years. Remission was seen in 34.3% of patients and was independently related to age 60 and older (odds ratio (OR) 3.2; 95% confidence interval (CI), 1.2-8.7) and inversely to the presence of rheumatoid factor (RF) (OR 8.3; 95% CI, 3.2-21.3 for persistent arthritis). Patients with two SE were likely to have persistent arthritis (P=0.006), but this was not significant when corrected for RF. Independent predictors for erosions at 3 years were RF (OR 7.5; 95% CI, 1.9-29.5) and area under the curve for number of swollen joints (OR 1.08; 95% CI, 1.02-1.16). SE status was not predictive of erosions at 3 years (OR 1.6; 95% CI, 0.7-3.7). In univariate analysis, patients possessing DERAA motif on DRB1 were less likely to have erosive disease than without this motif at 4 years (OR 0.21; 95% CI, 0.0-0.9, P=0.037) but this finding was partly explained by adjusting for RF (adjusted OR 0.24; 95% CI 0.04-1.37). In this study of recent onset IA, active disease and RF were associated with poor outcome. Whilst SE did not predict erosive disease, patients with DERAA motif may be protected against erosions whilst the presence of two SE alleles suggests persistence of arthritis.

Age of Onset↗

PubMed1999

Antibodies to type II collagen and HLA disease susceptibility markers in rheumatoid arthritis.

OBJECTIVE: To seek associations between antibodies to native and denatured type II collagen (NCII and DCII) and HLA in rheumatoid arthritis (RA). METHODS: One hundred fourteen patients with clinically well-defined RA were HLA-DR and DQ typed. Those who were DR4 positive were subtyped for DRB1*0401-*0408 alleles by polymerase chain reaction using allele-specific oligonucleotide probes. Antibodies to human NCII and DCII (heat-denatured) were measured by enzyme-linked immunosorbent assay. The frequency of HLA alleles was compared in patients grouped according to the presence and absence of antibodies to NCII and DCII. RESULTS: Twenty-seven patients (24%) were positive for antibodies to NCII. There was a significant increase in the frequency of HLA-DR7 in anti-NCII-positive patients compared with anti-NCII-negative patients (30% versus 9%; P = 0.019) and a significant decrease in HLA-DR3 (7% versus 28%; P = 0.044). Repeating the analyses after excluding the 16 patients who were DR7 positive revealed a significant increase in the frequency of HLA-DR1 in anti-NCII-positive patients compared with anti-NCII-negative patients (63% versus 27%; P = 0.045). Moreover, antibodies to NCII were associated with the third hypervariability region susceptibility sequence QRRAA that is present in DRB1*0101, *0404, *0405, and *0408 (84% versus 47%; P = 0.0085); 24 of 27 anti-NCII-positive patients were positive for either DR7, DR1, or DRB1*0404 or *0408. Thirty patients (26%) were positive for antibodies to DCII. There was a significant increase in the frequency of HLA-DR3 in anti-DCII-positive patients compared with anti-DCII-negative patients (40% versus 18%; P = 0.028). CONCLUSION: The genetic associations between HLA-DR alleles and antibodies to CII in RA patients is in keeping with the collagen-induced arthritis model and implicates autoimmunity to CII as a major component in the multifactorial pathogenesis of RA.

Alleles↗

PubMed1999

Risk factors for osteoporosis and fracture in patients attending rheumatology outpatient clinics.

BACKGROUND: Bone mineral density (BMD) using dual energy X-ray absorptiometry (DXA) scanning is the best predictor of osteoporotic fracture but may not be cost effective for all patient groups. Risk factors (RF) other than BMD may be useful for fracture prediction. AIM: To assess the prevalence of RF for osteoporosis (OP) and fracture in patients attending a public hospital rheumatology clinic and to document physician awareness of these RF. METHODS: Two hundred and twenty rheumatology outpatients completed a self-administered questionnaire pertaining to known RF for OP and fracture. Initiatives were documented by the treating rheumatologist. RESULTS: One hundred and fifty-four females and 66 males completed questionnaires: 57% had an inflammatory disorder and 32% had received significant glucocorticoid therapy. Forty-five (68%) males and 126 (82%) females had three or more RF for OP and fracture. Diagnosis of rheumatoid arthritis or connective tissue disorder (CTD) was the variable most significantly associated with increasing numbers of RF. Antiosteoporotic medication (AOM) use at assessment (64/219, 29.2%) was accounted for primarily by the use of hormone replacement therapy in females between 45-54 years. Prednisolone use predicted intervention in 103 (48%) patients. CONCLUSION: Many rheumatology outpatients have multiple RF for OP and fracture. Infrequent AOM use could be explained by inadequate awareness of high risk patients and the lack of an ideal long term agent. With restricted outpatient resources, the feasibility of identifying high risk patients for OP and fracture would increase if the hierarchical status of RF was better understood.

Adolescent↗

PubMed1997

The effect of HLA-DRB1 disease susceptibility markers on the expression of RA.

The study was designed to examine the effect on clinical expression of rheumatoid arthritis (RA) of HLA alleles, particularly DR4 and DR1 that contain susceptibility sequences for RA in the third hypervariable region (HVR3) of HLA-DRB1. We studied 114 consecutive Australian patients with RA attending a hospital outpatient clinic. The effects on indices of disease severity and activity of HLA DR4 and DR1, the DRB1*04 subtypes, and the polymorphism in the RA susceptibility sequence (QRRAA or QKRAA) were examined. The patients were initially divided into 6 groups, DR4,4; DR4,1; DR1,1; DR4/X; DR1,X, and DRX/X, and then further subdivided according to the actual HVR3 susceptibility sequence. The high risk conferred by the HVR3 susceptibility sequence, present in 76%, was confirmed, but 24% of the patients with long-standing seropositive erosive RA lacked this sequence. Among these those with DR2 had early-onset severe disease, and those with DR3 had late-onset milder disease. Differences in expression correlated with polymorphisms in the susceptibility sequence, in that active RA was associated more with QRRAA than QKRAA. There was no correlation of any HLA allele with disease severity. Our finding that the presence of the HVR3 sequence confers susceptibility and also influences the clinical expression and tempo of progression of RA suggests a role in pathogenesis for antigen presentation, whether of an autoantigenic molecule or a persisting infection.

Adult↗

PubMed1992

Epitope specificity of antibodies to type II collagen in rheumatoid arthritis and systemic lupus erythematosus.

Antibodies to human type II collagen were examined in the sera of 105 patients with rheumatoid arthritis (RA), 44 patients with systemic lupus erythematosus (SLE) and 11 patients who fulfilled the criteria of both diseases (RA-SLE overlap), using a solid-phase radioimmunoassay (RIA). The frequencies of antibodies to native and denatured human type II collagen were 20% and 27% in RA, 14% and 16% in SLE, and 45% and 36% in RA-SLE overlap. The specificity of the antibodies was further examined by inhibition with native and denatured type II collagen, by immunoblotting on native and denatured type II collagen, and by immunoblotting on cyanogen-bromide derived polypeptides of type II collagen. We could not identify any disease-specific patterns of reactivity. Thus, in the three disease groups the antibody response was polyclonal; there were antibody populations that reacted with native and/or denatured collagen, and epitopes could be assigned to at least three CB peptides, CB10.5, CB11 and CB8.

Antibodies↗

PubMed1992

Coexistent rheumatoid arthritis and systemic lupus erythematosus: clinical, serological, and phenotypic features.

The clinical and serological features and HLA phenotypes are reported for 11 patients with coexistent features of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). All patients had a symmetrical small joint polyarthritis and features of SLE such as rash, photosensitivity, oral ulceration, serositis, cytopenia, and biopsy proved lupus nephritis. Eight had hypocomplementaemia. Autoantibodies were characteristic of the two diseases: all patients had rheumatoid factor and antibodies to double stranded DNA, eight (73%) had antibodies to collagen, and five (46%) had antibodies to Ro (SS-A). There was also an overlap of HLA phenotypes. Six patients were DR4 and seven were DR2 or DR3 positive, and of the five patients who were DR4 negative, four shared class I alleles often associated with DR4. If RA and SLE share a common autoimmune dysfunction, those patients who have the two diseases do so because they have genetic determinants of both.

Antibodies, Antinuclear↗

PubMed1985

Popliteal cysts and deep venous thrombosis: Tc-99m red blood cell venography.

Thirty-four patients who clinically were suspected of having deep venous thrombosis (DVT) underwent Tc-99m red blood cell (RBC) venography followed by contrast venography. The sensitivity (88%) and specificity (94%) of Tc-99m RBC venography for DVT confirmed findings of previous studies. Twenty-four patients who had proved popliteal cysts and swollen calves also were examined using Tc-99m RBC venography. Large cysts (greater than 9 X 4 X 4 cm) showed lack of DVT features, photon deficient cold areas in the popliteal fossa, and diversion of venous flow around the photon deficient area. These features were seen in 25% of the study population (six patients), and assisted in the distinction between the two conditions.

Adult↗

PubMed1984

Psoriatic arthritis and myasthenia gravis.

A B27 positive woman, with a past history of myasthenia gravis and thymectomy, was found to have psoriatic arthritis. The implications of this association are briefly discussed.

Arthritis↗

PubMedDate not supplied

New bone formation in acromegaly: pathogenetic implications for diffuse idiopathic skeletal hyperostosis.

Radiographs of spinal and heel entheseal areas and the skull were examined for new bone formation in 30 acromegalic patients. Forty-seven percent satisfied accepted criteria for Diffuse Idiopathic Skeletal Hyperostosis (DISH), 67% had marked heel enthesopathic change and 87% had Hyperostosis Frontalis Interna (HFI). Such hyperostotic changes were indistinguishable from those seen in DISH and the extent and degree of such changes increased with duration of acromegaly. It is proposed that a common metabolic factor, e.g., hyperinsulinaemia, may be responsible for the hyperostotic changes seen in both DISH and acromegaly.

Acromegaly↗