Biomedical subjects

Anisur Rahman

Publications and source records attributed to Anisur Rahman.

At least 19 recordsLinked to original sources

PubMed2007

Binding of antiphospholipid antibodies to discontinuous epitopes on domain I of human beta(2)-glycoprotein I: mutation studies including residues R39 to R43.

OBJECTIVE: Pathogenic antiphospholipid antibodies (aPL) bind the self antigen N-terminal domain (domain I) of beta(2)-glycoprotein I (beta(2)GPI), with residues G40-R43 being important. However, peptides homologous to other regions of domain I have also been shown to bind aPL. Furthermore, there are no published reports of the effects of altering R39, which has greater surface exposure than the G40-R43 residues. METHODS: We used a novel, efficient method of production and purification of human domain I by Escherichia coli to create multiple mutants of domain I. These domain I mutants were then screened for binding to a range of polyclonal IgG purified from patients with antiphospholipid syndrome, using both solid-phase and fluid-phase assays. RESULTS: E coli-expressed purified domain I selectively bound IgG derived from patients with antiphospholipid syndrome. In region R39-R43, the R39S mutation had the greatest effect in terms of reducing binding to a panel of aPL in the fluid phase (mean +/- SD inhibition 14 +/- 18.5% versus 44.1 +/- 31.7% for G40E and 62.9 +/- 25.7% for wild-type domain I). Conversely, altering both D8 and D9 to S8 and G9, respectively, had the effect of enhancing binding to aPL in the fluid phase. Adding the remainder of the domain I-II interlinker resulted in enhanced binding over wild-type in the solid phase but not the fluid phase. CONCLUSION: The binding of aPL to beta(2)GPI domain I is complex and likely to involve discontinuous epitopes that include R39 in addition to G40-R43, the domain I-II interlinker, and possibly D8 and D9. Domain I variants with enhanced binding to aPL compared with wild-type domain I may aid in the development of novel therapies.

Antibodies, Antiphospholipid↗

PubMed2006

Prevalence of conventional and lupus-specific risk factors for cardiovascular disease in patients with systemic lupus erythematosus: A case-control study.

OBJECTIVE: Patients with systemic lupus erythematosus (SLE) are significantly more likely to experience a myocardial infarction or a stroke than age-matched controls. We compared the prevalence of conventional and lupus-specific risk factors in patients with SLE just before a cardiovascular event and in matched controls with SLE but no cardiovascular disease (CVD). METHODS: Twenty-nine patients with SLE and CVD were enrolled. For each patient, 2 ethnically- and sex-matched controls were obtained, 1 matched for age and 1 for SLE duration. Data regarding risk factors were collected for the time immediately preceding the relevant cardiovascular event, or at an equivalent time for controls. RESULTS: Patients' median age at event was 49 years (interquartile range 43-54 years) and mean disease duration was 12.0 +/- 7.1 years. Patients with SLE and CVD were more likely than both age and duration controls to be treated for hypertension (P = 0.01 and P = 0.001, respectively) and to have elevated triglyceride levels (P = 0.05 and P = 0.01, respectively). Compared with duration controls, CVD patients were more likely to have lupus anticoagulant (P = 0.03), but less likely to be receiving treatment with hydroxychloroquine (P = 0.003). Compared with age controls, patients were more likely to be current smokers (P = 0.03), to have taken a mean dosage >7.5 mg/day of prednisolone (P = 0.04), and to have been treated with pulsed methylprednisolone (P = 0.03). In multivariable analysis, only hypertension treatment was an independent risk factor for CVD. CONCLUSION: We identified significantly increased prevalence of some conventional and lupus-specific risk factors in patients with SLE immediately before a CVD event compared with controls matched for age or disease duration.

Adult↗

PubMed2006

Arginine residues are important in determining the binding of human monoclonal antiphospholipid antibodies to clinically relevant antigens.

In the antiphospholipid syndrome (APS), antiphospholipid Abs (aPL) bind to anionic phospholipids (PL) and various associated proteins, especially beta(2)-glycoprotein I (beta2GPI) and prothrombin. In the present study, we show that altering specific Arg residues in the H chain of a human pathogenic beta2GPI-dependent aPL, IS4, has major effects on its ability to bind these clinically important Ags. We expressed whole human IgG in vitro by stable transfection of Chinese hamster ovary cells with expression plasmids containing different V(H) and V(L) sequences. V(H) sequences were derived from IS4 by altering the number of Arg residues in CDR3. V(L) sequences were those of IS4, B3 (anti-nucleosome Ab), and UK4 (beta2GPI-independent aPL). Binding of the expressed H/L chain combinations to a range of anionic, neutral, and zwitterionic PL, as well as prothrombin, beta2GPI, dsDNA, and chicken OVA, was determined by ELISA. Of four Arg residues in IS4VH CDR3 substituted to Ser, two at positions 100 and 100g, reduced binding to all Ags, while two at positions 96 and 97 reduced binding to beta2GPI but increased or decreased binding to different PL. Eleven of 14 H/L chain combinations displayed weak binding to OVA with Arg to Ser replacements of all four Arg residues enhancing binding to this Ag. Only one H/L chain combination bound neutral PL and none bound dsDNA; hence, these effects are particularly relevant to Ags important in antiphospholipid syndrome. We hypothesize that these four Arg residues have developed as a result of somatic mutations driven by an Ag containing both PL and beta2GPI.

Amino Acid Substitution↗

PubMed2006

Articular presentation of disseminated histoplasmosis.

Histoplasmosis is an important opportunistic disease to consider in immunocompromised patients from endemic areas. Articular presentations of disseminated histoplasmosis are uncommon. We describe the case of a renal transplant recipient originating from South Africa in whom a suppurative arthritis presented as a manifestation of disseminated histoplasmosis.

Arthritis, Infectious↗

PubMed2006

Systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a clinically heterogeneous disease, which is autoimmune in origin and is characterized by the presence of autoantibodies directed against nuclear antigens. It is a multi-system disease, and patients can present in vastly different ways. Prevalence varies with ethnicity, but is estimated to be about 1 per 1000 overall with a female to male ratio of 10:1. The clinical heterogeneity of this disease mirrors its complex aetiopathogenesis, which highlights the importance of genetic factors and individual susceptibility to environmental factors. SLE can affect every organ in the body. The most common manifestations include rash, arthritis and fatigue. At the more severe end of the spectrum, SLE can cause nephritis, neurological problems, anaemia and thrombocytopaenia. Over 90% of patients with SLE have positive anti-nuclear antibodies (ANA). Significant titres are accepted to be of 1:80 or greater. SLE is a relapsing and remitting disease, and treatment aims are threefold: managing acute periods of potentially life-threatening ill health, minimizing the risk of flares during periods of relative stability, and controlling the less life-threatening, but often incapacitating day to day symptoms. Hydroxychloroquine and non-steroidal anti-inflammatory drugs are used for milder disease; corticosteroids and immunosuppressive therapies are generally reserved for major organ involvement; anti-CD20 monoclonal antibody is now used in patients with severe disease who has not responded to conventional treatments. Despite enormous improvements in prognosis since the introduction of corticosteroids and immunosuppressive drugs, SLE continues to have a significant impact on the mortality and morbidity of those affected.

Adult↗

PubMed2006

A novel expression system of domain I of human beta2 glycoprotein I in Escherichia coli.

BACKGROUND: The antiphospholipid syndrome (APS), characterised by recurrent miscarriage and thrombosis, is a significant cause of morbidity and mortality. Domain I (DI) of human beta 2 glycoprotein I (beta2GPI) is thought to contain crucial antibody binding epitopes for antiphospholipid antibodies (aPL), which are critical to the pathogenesis of APS. Expressing this protein in bacteria could facilitate studies investigating how this molecule interacts with aPL. METHODS: Using a computer programme called Juniper, sequentially overlapping primers were designed to be used in a recursive polymerase chain reaction (PCR) to produce a synthetic DI gene. Specifically Juniper incorporates 'major' codons preferred by bacteria altering 41 codons out of 61. This was cloned into the expression plasmid pET(26b) and expressed in BL21(DE3) Escherichia coli (E. coli). By virtue of a pelB leader sequence, periplasmic localisation of DI aided disulphide bond formation and toxicity was addressed by tightly regulating expression through the high stringency T7lac promoter. RESULTS: Purified, soluble his-tagged DI in yields of 750 microg/L bacterial culture was obtained and confirmed on Western blot. Expression using the native human cDNA sequence of DI in the same construct under identical conditions yielded significantly less DI compared to the recombinant optimised sequence. This constitutes the first description of prokaryotic expression of soluble DI of beta2GPI. Binding to murine monoclonal antibodies that recognise conformationally restricted epitopes on the surface of DI and pathogenic human monoclonal IgG aPL was confirmed by direct and indirect immunoassay. Recombinant DI also bound a series of 21 polyclonal IgG samples derived from patients with APS. CONCLUSION: By producing a synthetic gene globally optimised for expression in E. coli, tightly regulating expression and utilising periplasmic product translocation, efficient, soluble E. coli expression of the eukaryotic protein DI of beta2GPI is possible. This novel platform of expression utilising pan-gene prokaryote codon optimisation for DI production will aid future antigenic studies. Furthermore if DI or peptide derivatives of DI are eventually used in the therapeutic setting either as toleragen or as a competitive inhibitor of pathogenic aPL, then an E. coli production system may aid cost-effective production.

Amino Acid Sequence↗

PubMed2006

Revised British Isles Lupus Assessment Group 2004 index: a reliable tool for assessment of systemic lupus erythematosus activity.

OBJECTIVE: To test the interrater reliability of the revised British Isles Lupus Assessment Group 2004 (BILAG-2004) index for the assessment of systemic lupus erythematosus (SLE) activity. METHODS: Patients with SLE were recruited from 11 centers. Two physician raters separately assessed the patients' disease activity using the BILAG-2004 index in routine clinical practice. Scores ranged from A (for very active disease) to E (for inactivity). Two reliability exercises were performed. Changes were made to the index after the first exercise (E1), and additional training was provided to the raters before the second exercise (E2). E1 and E2 involved 12 and 14 raters, respectively. Interrater reliability was assessed using kappa statistics and intraclass correlation coefficients. Levels of agreement and the extent of major disagreement were also examined. Major disagreement was defined as a score difference between raters of A versus C, D, or E or B versus D or E. RESULTS: For each exercise, 97 patients were recruited. In E1, the mean age of the patients was 42.3 years (range 18.5-82.2 years), 89.7% were women, and 74.2% were white, 8.2% were Afro-Caribbean, and 13.4% were South Asian, and in E2, the mean age was 43.7 years (range 17.7-75 years), 90.7% were women, and 68% were white, 15.5% were Afro-Caribbean, and 11.3% were South Asian. The mean disease duration was 9.4 years (range 0-32.1 years) for patients in E1 and 10 years (range 0-34.8 years) in E2. There was improvement in the interrater reliability and the level of agreement from E1 to E2. Further improvement was achieved after removal of poorly performing items. CONCLUSION: The BILAG-2004 index is a reliable tool to assess SLE activity. The use of a well-defined glossary and training of raters are essential to ensure the optimal performance of the index.

Activities of Daily Living↗

PubMed2006

Systemic lupus erythematosus--2005 annus mirabilis?

We are about to enter a new era in the treatment of patients with systemic lupus erythematosus (SLE). For the past 40 years hydroxychloroquine sulfate and corticosteroids, together with varying combinations of immunosuppressive drugs, have been the main treatments for SLE. Although effective for many patients, some patients fail to respond to these drugs and even more suffer from major side effects due to the generalized nature of the immunosuppression. In this article we review the remarkable confluence of new therapies ranging from newer immunosuppressive drugs with fewer side effects, such as mycophenolate mofetil, to the more targeted approaches offered by biological agents. These agents have been designed to block molecules such as CD20, CD22 and interleukin-10 that are thought to have an integral part in the development of SLE. This wolf might not yet be about to become extinct but its survival is increasingly under threat!

Clinical Trials as Topic↗

PubMed2006

Arsenic exposure in pregnancy: a population-based study in Matlab, Bangladesh.

This study assessed the exposure of pregnant women to arsenic in Matlab, Bangladesh, an area with highly-elevated concentrations of arsenic in tubewells, by measuring concentrations of arsenic in urine. In a defined administrative area, all new pregnancies were identified by urine test in gestational week 6-8, and women were asked to participate in the assessment of arsenic exposure. Urine for analysis of arsenic was collected immediately and in gestational week 30. In total, 3,426 pregnant women provided urine samples during January 2002-March 2003. There was a considerable variation in urinary concentrations of arsenic (total range 1-1,470 microg/L, adjusted to specific gravity 1.012 g/mL), with an overall median concentration of 80 microg/L (25th and 75th percentiles were 37 and 208 microg/L respectively). Similar concentrations were found in gestational week 30, indicating no trend of decreasing exposure, despite the initiation of mitigation activities in the area. Arsenic exposure was negatively associated with socioeconomic classes and achieved educational level. There were marked geographical variations in exposure. The results emphasize the urgent need for efficient mitigation activities and investigations of arsenic-related reproductive effects.

Adolescent↗

PubMed2005

"It struck me that they didn't understand pain": the specialist pain clinic experience of patients with chronic musculoskeletal pain.

OBJECTIVE: To explore the experiences of diagnosis and management among patients who attended a specialist musculoskeletal pain clinic and the factors influencing their interpretation of these experiences. METHODS: A postal questionnaire was sent to potential participants 6-20 months after their first clinic attendance. Data were collected on pain presence, severity, and location; health-related quality of life; psychological distress; and care-seeking behavior. Questionnaire data were used to inform combined purposive and theoretical sampling. In-depth interviews were conducted that probed participants' understanding of their chronic musculoskeletal pain and its management in a specialist musculoskeletal pain clinic. RESULTS: Fifteen patients were interviewed. Four main themes were identified: spoiled identity (pain limited patients' activities so extensively that it affected their sense of self); diminishing faith in medicine (patients were disappointed with aspects of their care-seeking experience); making sense of pain (patients made sense of their pain by locating their pain within the context of their lives); and learning to live with the pain (an issue for all patients was whether or not their pain would stop or whether they had to learn to live with it). CONCLUSION: Developing, implementing, and evaluating approaches to address patients' spoiled identities might allow us to improve patient-centered outcomes in chronic musculoskeletal pain.

Activities of Daily Living↗

PubMed2005

Stable expression of a recombinant human antinucleosome antibody to investigate relationships between antibody sequence, binding properties, and pathogenicity.

When purified under rigorous conditions, some murine anti-double-stranded-DNA (anti-dsDNA) antibodies actually bind chromatin rather than dsDNA. This suggests that they may actually be antinucleosome antibodies that only appear to bind dsDNA when they are incompletely dissociated from nucleosomes. Experiments in murine models suggest that antibody-nucleosome complexes may play a crucial role in the pathogenesis of glomerulonephritis in systemic lupus erythematosus. Some human monoclonal anti-DNA antibodies are pathogenic when administered to mice with severe combined immunodeficiency (SCID). Our objective was to achieve stable expression of sequence-altered variants of one such antibody, B3, in Chinese hamster ovary (CHO) cells. Purified antibodies secreted by these cells were tested to investigate whether B3 is actually an antinucleosome antibody. The pathogenic effects of the antibodies were tested by implanting CHO cells secreting them into SCID mice. Purified B3 does not bind to dsDNA unless supernatant from cultured cells is added, but does bind to nucleosomes. The strength of binding to dsDNA and nucleosomes is dependent on the sequence of the light chain. Mice that received CHO cells secreting wild-type B3 developed more proteinuria and died earlier than control mice that received nonsecreting CHO cells or mice that received B3 with a single light chain mutation. However, none of the mice had histological changes or deposition of human immunoglobulin G in the kidneys. Sequence changes may alter the pathogenicity of B3, but further studies using different techniques are needed to investigate this possibility.

Animals↗

PubMed2005

Fresh tympanic membrane perforations heal without significant loss of strength.

HYPOTHESIS: The mechanical and structural properties of the tympanic membrane change after a perforation has healed. BACKGROUND: In previous studies, efforts have been made to enhance the healing process of tympanic membrane perforations. The strength of the healed perforation has been tested with moiré interferometry in gerbils, but in no other species. METHODS: A laser myringotomy was made on 10 Sprague-Dawley rats and 10 CBA mice, and assessments were made after 2 or 4 weeks with moiré interferometry and light and electron microscopy. RESULTS: The mean peak displacement at pressure loads of +350 daPa and of -350 daPa did not differ significantly in the healed perforations as compared with the untouched tympanic membranes. Morphologic assays showed fivefold increased thickness at the site of the perforation due to invaded fibroblasts and extracellular matrix. CONCLUSION: Moiré interferometry was successfully performed in the rat ears, whereas in mouse ears the method was not easily applicable due to technical difficulties. The stress-strain curve of the rat tympanic membrane displays an S-shape. The strength of the spontaneously healed tympanic membrane after myringotomy was not significantly impaired. The site of the perforation became significantly thickened at 2 and 4 weeks post-myringotomy. This information is of clinical importance, because recently closed perforations will be challenged by pressure gradient in everyday life.

Animals↗

PubMed2005

Steroidogenesis in ovarian follicles of chub mackerel, Scomber japonicus.

We incubated different radiolabeled steroid precursors with intact chub mackerel ovarian follicles to clarify the synthetic pathways of steroid hormones during vitellogenesis and following final oocyte maturation (FOM). During vitellogenesis, estradiol-17beta (E2) was synthesized from pregnenolone via 17-hydroxypregnenolone, 17-hydroxyprogesterone, androstenedione, and testosterone. The physiological significance of the intermediate metabolites of E2 in the ovarian follicles was examined by comparing follicular steroidogenesis between gonochoric and hermaphroditic fish species. After vitellogenesis, the steroidogenic pathway shifted from E2 to maturation-inducing hormone (MIH) production owing to the inactivation of 17,20-lyase and the activation of 20 beta-hydroxysteroid dehydrogenase. Of the new steroids produced during FOM, 17,20beta-dihydroxy-4-pregnen-3-one (17,20beta-P) was most effective at inducing germinal vesicle breakdown in vitro. Circulating levels of 17,20beta-P increased specifically around the time of germinal vesicle migration, while another FOM-specific 20beta-hydroxylated progestin, 17,20beta,21-trihydroxy-4-pregnen-3-one, was present at consistently low levels during FOM. These results indicate that 17,20beta-P is the MIH of chub mackerel.

Analysis of Variance↗

PubMed2004

The critical role of arginine residues in the binding of human monoclonal antibodies to cardiolipin.

Previously we reported that the variable heavy chain region (VH) of a human beta2 glycoprotein I-dependent monoclonal antiphospholipid antibody (IS4) was dominant in conferring the ability to bind cardiolipin (CL). In contrast, the identity of the paired variable light chain region (VL) determined the strength of CL binding. In the present study, we examine the importance of specific arginine residues in IS4VH and paired VL in CL binding. The distribution of arginine residues in complementarity determining regions (CDRs) of VH and VL sequences was altered by site-directed mutagenesis or by CDR exchange. Ten different 2a2 germline gene-derived VL sequences were expressed with IS4VH and the VH of an anti-dsDNA antibody, B3. Six variants of IS4VH, containing different patterns of arginine residues in CDR3, were paired with B3VL and IS4VL. The ability of the 32 expressed heavy chain/light chain combinations to bind CL was determined by ELISA. Of four arginine residues in IS4VH CDR3 substituted to serines, two residues at positions 100 and 100 g had a major influence on the strength of CL binding while the two residues at positions 96 and 97 had no effect. In CDR exchange studies, VL containing B3VL CDR1 were associated with elevated CL binding, which was reduced significantly by substitution of a CDR1 arginine residue at position 27a with serine. In contrast, arginine residues in VL CDR2 or VL CDR3 did not enhance CL binding, and in one case may have contributed to inhibition of this binding. Subsets of arginine residues at specific locations in the CDRs of heavy chains and light chains of pathogenic antiphospholipid antibodies are important in determining their ability to bind CL.

Amino Acid Sequence↗

PubMed2004

Is alpha-actinin a target for pathogenic anti-DNA antibodies in lupus nephritis?

OBJECTIVE: Following recent reports that pathogenic murine anti-DNA antibodies bind to alpha-actinin, it was obviously of interest to assess the ability of human pathogenic anti-double-stranded DNA (anti-dsDNA) antibodies to bind this antigen. Both human monoclonal anti-DNA antibodies and antibodies affinity purified from the sera of patients with systemic lupus erythematosus (SLE) were investigated. METHODS: An enzyme-linked immunosorbent assay was established to measure immunoglobulin binding to alpha-actinin. Antibodies binding dsDNA were purified from the sera of SLE patients who either had active renal disease or had never had renal disease. Serum samples were selected at times when the patients' sera exhibited high IgG binding to dsDNA. The binding of supernatants from 3 high-affinity human anti-dsDNA IgG hybridomas (RH14, B3, and DIL-6) and 7 human IgM anti-DNA hybridomas was also investigated. RESULTS: A greater proportion of anti-dsDNA IgG-binding antibodies purified from patients with renal disease bound to alpha-actinin than did those purified from the sera of patients without renal disease. The specificity of binding to the 100-kd alpha-actinin molecule was confirmed by Western blotting. The pathogenic human antibodies RH14 and B3 bound strongly to alpha-actinin, while nonpathogenic DIL-6 bound very weakly. RT84, the IgM antibody that binds dsDNA with the highest affinity, exhibited the greatest binding to alpha-actinin. CONCLUSION: The results of our study support the findings of previous studies using murine anti-DNA monoclonal antibodies, which suggest that pathogenic anti-dsDNA antibodies cross-react with alpha-actinin.

Actinin↗

PubMed2004

Somatic mutations to arginine residues affect the binding of human monoclonal antibodies to DNA, histones, SmD and Ro antigen.

Autoantibodies to a wide variety of antigens are associated with systemic lupus erythematosus (SLE). Antibodies to double-stranded DNA (anti-dsDNA) are thought to be particularly closely related to tissue damage and disease activity in SLE. Autoantibodies to histones, Sm and Ro are found in patients with SLE, but their role in pathogenesis is unclear. Using a transient expression system, we previously showed that particular sequence motifs in CDRs of light chains derived from the human Vlambda gene 2a2 are very important in determining their ability to form a DNA-binding site, when paired with the heavy chain of the human monoclonal anti-dsDNA antibody B3. These motifs are often sites of somatic mutation and/or contain arginine residues. In the experiments reported in this paper, the same expression system was used to show that these CDR motifs also affect binding to histones, Ro antigen and Sm antigen, but that binding to different antigens is affected in diverse ways by particular changes in the sequence of the CDRs. The heavy chain also plays a role in binding to these antigens. Pairing of the same range of 11 2a2 derived light chains with the heavy chain of a different anti-DNA antibody, 33.H11, gave reduced ability to bind DNA in comparison with the results obtained using the B3 heavy chain. Computer-generated models of the three-dimensional structures of these heavy/light chain combinations were used to define the positions occupied by the important sequence motifs at the binding sites of these antibodies, and to explain the different effects exerted by arginine residues at different positions in the light chains.

Amino Acid Sequence↗

PubMed2004

Common patterns of B cell perturbation and expanded V4-34 immunoglobulin gene usage in autoimmunity and infection.

Features of the lymphocyte population in systemic lupus erythematosus (SLE) include a disordered B cell profile and production of autoantibodies. An additional distinctive perturbation is the overexpression of V4-34-encoded serum immunoglobulins (Ig). A similar rise in V4-34-encoded Ig occurs in normal subjects following infection with certain herpesviruses, and is found in Epstein-Barr virus (EBV)-associated infectious mononucleosis (IM). To assess common and distinctive features of B cells in patients with SLE and IM, we compared the B cell profile and V4-34 gene involvement in patients with SLE and IM. B cell profiles from patients with IM paralleled those of patients with SLE, showing a differential loss of naïve and memory B cells and the maintenance of plasmablast/early plasma cells. Class-switched V4-34-encoded IgG from plasmablast/early plasma cells was evident both in patients with SLE and IM and revealed common features of oligoclonal expansions with most having undergone somatic hypermutation. It has been proposed that, in healthy individuals, expression of the V4-34 gene is specifically censored prior to isotype switch as a control on autoreactivity. If so, censoring is bypassed following EBV infection, after which equilibrium is restored. Continuing high serum levels in SLE may arise either by disordered regulation, or by subclinical reactivation of endogenous virus.

Amino Acid Sequence↗

PubMed2004

Important determinants of self-efficacy in patients with chronic musculoskeletal pain.

OBJECTIVE: To define the presenting characteristics of a population of patients with chronic musculoskeletal pain seen in a tertiary rheumatology clinic, and to investigate which factors are associated with self-efficacy in these patients. METHODS: Data were collected prospectively for 196 patients who attended the clinic for the first time between October 2000 and August 2002. The primary outcome measure was self-efficacy, measured using the Pain Self-Efficacy Questionnaire. Secondary outcome measures were pain intensity and disability due to pain. The data were analyzed using both univariate and multiple regression methods. RESULTS: These patients had typically undergone extensive investigations and tried various therapies but were left with persisting pain and poor self-efficacy. Multiple regression analysis showed that after adjustment for other factors, the presence of depressive symptoms and employment status were associated with self-efficacy. Patients who reported depressive symptoms had mean self-efficacy scores 7.0 units lower (95% confidence interval, CI: 2.2-11.9) than those who did not. Being employed was associated with higher self-efficacy. The retired had scores 8.3 units lower than employed people (95% CI: 2.4-14.2), whereas housewives and the unemployed had scores approximately 14 units lower (95% CI: 8.0-20.9 and 7.5-19.0, respectively) than employed people. There was also some evidence that distribution of painful sites was associated with self-efficacy. Patients with extensive pain had scores 4.1 units (95% CI: -0.4-8.6) lower than those with limited pain. CONCLUSION: Depressive symptoms, occupational status, and possibly distribution of pain are associated with the reported confidence of these patients with chronic pain in their ability to carry out everyday activities. Possible links to the idea of legitimacy of pain are discussed.

Activities of Daily Living↗