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ID PMID Title PublicationDate abstract
11500851 Effects of paclitaxel on cultured synovial cells from patients with rheumatoid arthritis. 2001 Aug 1 BACKGROUND: Proliferation of synovial cells is considered to play a key role in rheumatoid arthritis (RA). Using paclitaxel, a unique antineoplastic agent known to suppress collagen-induced arthritis, we conducted an in vitro study of cell kinetics on cultured synovial cells from patients with RA. METHODS: Alterations of the cell cycle of cultured fibroblast-like synovial cells (FLSs) from patients with RA were studied using flow cytometry and laser scanning cytometry. Apoptosis and accumulation of cyclin concerning effects of paclitaxel were detected. RESULTS: Paclitaxel induced arrest of the cell cycle at G2/M phase and apoptosis in FLSs. The late stage of apoptosis was determined by the positivity of terminal deoxynucleotidyl transferase assay. Morphological observation by combined usage of both annexin V and propidium iodide on FLSs on a slide glass showed early apoptotic changes in detail. FLSs arrested at G2/M phase showed marked accumulation of cyclin B1. The effects of paclitaxel decreased on FLSs, which diminished proliferative activity. CONCLUSIONS: These data indicate that paclitaxel induces cell arrest at G2/M phase followed by apoptosis in human FLSs, which have high proliferative activity, and possible therapeutic effects of paclitaxel on RA.
10599370 Toxicity profile of methotrexate in rheumatoid arthritis. A preliminary survey. 1999 A number of patients with rheumatoid arthritis attending the Rheumatology Clinic at St Luke's Hospital are currently receiving the drug methotrexate as a second line disease-modifying agent. A survey has been conducted to assess the toxicity profile of methotrexate in 33 of these patients who were followed up for at least 1 year or until they developed side effects necessitating discontinuation of treatment. Adverse effects in this group of patients included haematological ones (6%), asymptomatic elevations of liver enzymes (57%), gastrointestinal (6%) and dermatological side effects (3%). These results have been compared to larger studies performed abroad. Regular monitoring of a complete blood count and liver function tests has helped to detect the more serious side effects of methotrexate at an early stage enabling successful intervention in these patients.
10432197 Low prevalence of clinicopathologic and sialographic changes in salivary glands of men wit 1999 Aug Sjögren's syndrome (SS) is uncommon in men and there are few reports that describe their clinical features. In the present study, we investigated salivary gland manifestations in men with SS and compared the results with those in women patients. This study included 12 men and 117 women with SS, and the mean stimulated parotid flow rate in men (4.1 ml/5 min, n = 10) was higher than that of the women (3.1 ml/5 min, n = 101). The prevalence of SS-related sialographic findings, such as globular and punctate sialectasis, was significantly (P<0.05) lower in men (3/11) than in women (72/117). The prevalence of grade 4 cases on labial salivary gland biopsy was also significantly (P<0.01) lower in men (4/11) than in women (82/111). These results indicate a lower prevalence of SS-related clinicopathologic and sialographic changes in men with SS than in women with the same condition.
11451137 Ten- to 14-year clinical followup of the cementless Natural Knee system. 2001 Jul Of 300 consecutive knees (238 patients) that had undergone arthroplasty with the cementless Natural Knee prosthesis from 1985 to 1989, 176 knees (141 patients) were available for followup at an average of 12 +/- 1 years after the operation. Knee function was improved significantly. Modified Hospital for Special Surgery knee scores improved from 59.1 +/- 13.2 points preoperatively to 97.8 +/- 4.7 points at last followup. At last followup, knee range of motion averaged 0 degrees +/- 2 degrees to 120 degrees +/- 10 degrees. Implant survival was 93.4% (including infection and simple polyethylene exchanges) and 95.1% (excluding infection and simple polyethylene exchanges) at 10 years when applying the Kaplan-Meier survival analysis, using loose components, revision, or both as failure criteria. Besides the three revisions for infection, only two femoral and one tibial component required revision. The patellar component survivorship at 10 years was 95.1%. All patellar revisions were attributed to edge wear. Subsequent operative and design changes, including patellar component medialization and countersinking, have decreased the incidence of patellar revision. The long-term results of this cementless knee system compare favorably with those of cemented systems. The Natural Knee design has provided excellent and predictable long-term clinical results in the current series of active patients.
11451133 Long-term followup of the Miller-Galante total knee replacement. 2001 Jul One hundred seventy-two consecutive cemented Miller-Galante-I total knee arthroplasties in 155 patients were compared with 109 consecutive cemented Miller-Galante-II total knee arthroplasties in 92 patients. The average followup was 11 years (range, 8-15 years) and 9 years (range, 8-10 years), respectively. Of the 172 Miller-Galante-I arthroplasties, there have been 21 revisions; 15 patellar revisions; two included femoral revisions attributable to abrasion. Six additional well-fixed femoral and tibial components were revised: two for early instability, one for pain, one for periprosthetic fracture, and two for infection. No component had aseptic loosening or osteolysis. Using revision or loosening of any components as the end point, the Kaplan-Meier 10-year survivorship was 84.1% +/- 4.1%. Of the 109 Miller-Galante-II arthroplasties, there have been no component revisions, no aseptic loosening, and no osteolysis. Using revision or loosening of any components as the end point, the Kaplan-Meier 10-year survivorship was 100%. The Miller-Galante knee systems showed excellent fixation with no loosening and no osteolysis at as many as 15 years. Additionally, there have been no component revisions for late instability at as many as 15 years. Finally, the high prevalence of patellofemoral complications with the Miller-Galante-I design has been obviated with the Miller-Galante-II design.
10365782 Elimination of non-viable 6-thioguanine-sensitive T cells from viable T cells prior to PCR 1999 May 27 The study of T cell clones at the genomic level is expanding our understanding of their role in diseases such as rheumatoid arthritis (RA) and multiple sclerosis (MS). We have been carrying out genotypic analysis by PCR of hypoxanthine phosphoribosyltransferase (hprt) mutations in these cells. Mutant T cells in the population can be cloned on the basis of their resistance to the cytotoxic drug, 6-thioguanine-(6-TG). A difficulty is that the majority of primary human T cells are capable of only limited growth ex vivo, even in the presence of 'feeder' cells. PCR analysis of DNA from such clones is made difficult by the limited number of viable mutant (drug-resistant) T cells and the large number of dead (drug-sensitive) mononuclear cells and feeder cells. DNA from the 'dead' cells remains sufficiently intact for many weeks in culture and can represent a significant source of background in PCR analysis. Here we describe a method employing hypotonic shock and micrococcal nuclease that reliably eliminates non-viable 6-TG-sensitive cells, allowing the study of the hprt gene in < 200 T cells by PCR.
10555598 Minocycline and autoimmunity. 1999 Oct Minocycline is the most widely prescribed systemic antibiotic for the management of acne. In the past several years, increasing attention has been paid to the drug, both for its potential use as a disease-modifying antirheumatic agent and for its propensity to engender untoward autoimmune reactions, including serum sickness-like disease, drug-induced lupus, and autoimmune hepatitis. This paper reviews the evidence for minocycline as an anti-inflammatory and immunomodulatory agent, its utility in the treatment of rheumatoid arthritis, and the spectrum of adverse reactions that have been ascribed to the drug in the past 5 years.
9484654 Soluble recombinant neutral endopeptidase (CD10) as a potential antiinflammatory agent. 1998 Feb Several endogenous peptides, including bradykinin and substance P, have potent inflammatory effects in the joint. Levels of these peptides are regulated by plasma and cell-associated peptide degrading enzymes. One of these peptidases, neutral endopeptidase-24.11 (NEP-24.11), is expressed constitutively and in high density on human synovial cells and is presumed to play a critical role in local regulation of peptide levels in the joint. We examined the role of endogenous NEP-24.11 in regulating bradykinin-mediated effects in an articular model, and investigated the ability of soluble, recombinant human NEP-24.11 to augment the effects of the endogenous enzyme. Our studies demonstrate that endogenous synovial NEP-24.11 does not significantly modulate inflammatory peptide effects on cells when competing with colocalizing peptide receptors expressed in high density. Administration of excess, soluble recombinant NEP-24.11 can overcome this problem, however. Furthermore, the activity of the recombinant enzyme was not compromised in the presence of oxidants or inflammatory joint fluids. Recombinant NEP-24.11 holds promise as a novel therapeutic strategy for the treatment of inflammatory arthritis.
9831332 Possible background mechanisms of the effectiveness of cyclooxygenase-2 inhibitors in the 1998 Oct Cyclooxygenase (COX)-2 was induced in an acute exudative inflammatory model (rat carrageenin-induced pleurisy) in which prostaglandin E2, 6-keto-prostaglandin F1alpha, and thromboxane B2 were generated in the pleural fluid. Selective COX-2 inhibitors, such as NS-398, inhibited the plasma exudation and generation of prostaglandin E2, but not that of thromboxane B2 and 6-keto-prostaglandin F1alpha, in the pleural fluid. In proliferative inflammatory models, COX-2 was induced, and selective COX-2 inhibitors suppressed granuloma formation, particularly, microvessel formation. COX-2 was induced during angiogenesis in a sponge model implanted into skin of rat, and the COX-2 inhibitor suppressed the angiogenesis. As induction of COX-2 was reported in osteoblasts, COX-2 was involved in most characteristic responses of acute exudative inflammation, granuloma formation, bone resorption, and pain in rheumatoid arthritis. The prevention of these COX-2 responses provides a rationale for the effectiveness of COX-2 inhibitors in the treatment of rheumatoid arthritis.
9202064 Anti-A2/RA33 autoantibodies are directed to the RNA binding region of the A2 protein of th 1997 Jul 1 The recently described anti-A2/RA33 autoantibodies occur in 20-40% of patients with RA, SLE, and mixed connective tissue disease (MCTD). They are directed to the A2 protein of the heterogeneous nuclear ribonucleoprotein complex (hnRNP-A2), an abundant nuclear protein associated with the spliceosome. The NH2-terminal half of the antigen contains two conserved RNA binding domains whereas its COOH-terminal part is extremely glycine-rich. The aim of this study was to characterize the autoepitopes of hnRNP-A2 and to investigate the effects of anti-A2/RA33 autoantibodies on possible functions of the antigen. Using bacterially expressed fragments, two major discontinuous epitopes were identified. One containing the complete second RNA binding domain was recognized by the majority of patients with RA and SLE but not by patients with MCTD. The second epitope contained sequences of both RNA binding domains and was preferentially targeted by patients with MCTD. When the RNA binding properties of the antigen were investigated, oligoribonucleotides containing the sequence motif r(UUAG) were found to bind to a site closely adjacent or overlapping with the epitope targeted by autoantibodies from patients with RA and SLE. Moreover, anti-A2/RA33 autoantibodies from patients with RA or SLE, but not from patients with MCTD, inhibited binding of RNA. Thus, anti-A2/RA33 autoantibodies recognize conformation-dependent epitopes located in a functionally important region of the antigen. Furthermore, the specific recognition of an epitope by MCTD patients may be used as another argument in favor of considering MCTD a distinct connective tissue disease.
9697147 [Cementless hip prosthesis in inflammatory rheumatic diseases]. 1998 Jun We compared the outcome of cementless hip arthroplasty in patients with chronic rheumatic diseases (cases) and patients with osteoarthritis (controls). Between 1985 and 1993 we implanted 26 cementless hips in 22 patients with Rheumatoid Arthritis, Psoriatic Arthritis or Ankylosing Spondylitis. From a pool of more than 600 patients with Osteoarthritis we chose 40 matched controls (41 hips). Matching variables were year of implantation, age, follow-up, height, weight, gender and type of implant. At follow-up (cases: 58 +/- 27 months; controls: 56 +/- 26 Monate) no signs of loosening or migration of the stem were found, neither in the cases nor in the controls. Loose and/or migrated cups were found in 4 patients with rheumatic diseases (after 44, 65, 65 and 107 months) and in 3 patients with osteoarthritis (after 63, 84 and 100 months). Two cups were revised within 18 months in the control group, in the case group one revision was necessary after 5 years. Loosening and revision rates did not differ significantly (p > 0.20). Clinically, those with Osteoarthritis had a better extension (p < 0.02), were more satisfied with their (artificial) hips (p < 0.05) and did better in some activities of daily living (climbing stairs, dressing, sitting/standing up). Within a mean follow-up of 5 years the results of patients with chronic rheumatic diseases seem to be comparable to those of a matched control-group of patients with Osteoarthritis. Differences between the groups concern areas, in which rheumatic patients are handicapped due to their chronic illness. Nevertheless, we need long-term-results, before we can recommend cementless implants for these patients.
11037877 Decreased cellular activity and replicative capacity of osteoblastic cells isolated from t 2000 Oct OBJECTIVE: Periarticular osteopenia is frequently observed in rheumatoid arthritis (RA). Bone loss has been considered to be at least partly due to inadequate bone formation, which in turn, is largely dependent on the number of osteoblasts and the osteoblastic activity. Normal human somatic cells undergo a finite number of cell divisions and ultimately enter a nondividing state called replicative senescence. It has been proposed that the telomere, the terminal sequence of chromosomes, is the mitotic clock that triggers senescence. In the present study, we sought to clarify the relationship between periarticular osteopenia and osteoblast replicative senescence in RA. METHODS: We examined age-related changes in cellular activity (alkaline phosphatase activity, osteocalcin and C-terminal type I procollagen secretion, and cAMP response to parathyroid hormone), replicative capacity, and senescent cell expression in osteoblasts from periarticular bone samples obtained from 15 patients with RA and 15 age-matched patients with osteoarthritis (OA). Cellular replicative capacity was analyzed by the mean telomere length and in vitro remaining replicative lifespan of the cells. RESULTS: In both OA and RA groups, the cell proliferation rate, the levels of osteoblastic markers, mean telomere length, and replicative lifespan in osteoblastic cells gradually decreased with the increasing age of the donor. The percentage of senescent osteoblastic cells in the periarticular bone increased with age in both groups, and the rate of expression of senescent cells was higher in RA patients than in age-matched OA patients. The osteoblastic activities and replicative capacity of osteoblastic cells from RA patients were lower than those from OA patients at any donor age. The age-related decreases in the osteoblastic activity and replicative capacity of osteoblastic cells from periarticular bone were greater in RA patients than in OA patients. CONCLUSION: Our results suggest that osteoblast replicative senescence in periarticular bones occurs more rapidly with aging in RA than in OA patients and contributes to periarticular osteopenia in RA.
9562647 Plasma proteins glycosylation and its alteration in disease. 1997 Jan Most plasma proteins are glycoproteins, that is, they possess oligosaccharide chains attached to the polypeptide core. These oligosaccharides have important structural and functional roles; they serve as recognition markers (ligands), especially for lectin receptors, thus modulating the glycoprotein interactions. Protein glycosylation is a posttranslational event which depends on the proteic core and biosynthetic cell type and results in a set of microheterogeneous forms (glycoforms) of an individual glycoprotein. Under pathological conditions an alteration of the glycosylation pattern of plasma glycoproteins occurs. So, degalactosylated IgG and IgA1 detected in rheumatoid arthritis and IgA nephropathy, respectively, are implicated in the pathogenic mechanisms. Alteration of transferrin, alpha 1-acid glycoprotein and alpha-fetoprotein glycosylation (reduced sialylation and increased branching of oligosaccharide chains) occurs in liver diseases. In inflammations and infections the alteration is dependent on the disease studied, while increased sialylation and fucosylation of acute-phase proteins are detected in cancer sera. Lectin-based methods have been developed for clinical purposes, in order to improve the diagnosis, prognosis evaluation, or treatment monitoring.
10949441 Occipital bone graft for atlantoaxial fusion. 2000 BACKGROUND: Instability of the atlantoaxial segment is frequently encountered in neurosurgical practice. Numerous fusion techniques have been employed at this level. Most commonly, arthrodesis is achieved through bone and wire techniques. We have employed the use of suboccipital bone in lieu of iliac crest autograft in order to avoid the significant morbidity associated with iliac crest graft harvest. METHODS: Twenty one patients suffering instability from various etiologies underwent C1-C2 fusion at our institution using occipital bone graft and wire fixation. A small craniectomy was performed near the foramen magnum, and the bone graft was notched and secured in place using wire fixation. Patients were placed in a Philadelphia or Aspen collar for 6-12 weeks postoperatively, and flexion/extension plain film of the cervical spine were used to evaluate fusion. RESULTS: Long term follow up was available on all patients (mean 32 months, range 12-48 months). Fusion was achieved in 81% of patients within 12 weeks. Specifically, 71% (5/7) of rheumatoid patients were successfully fused. All patients with traumatic C1-C2 instability were fused. No complications were associated with the harvest of the occipital bone. CONCLUSION: The results of fusion via this technique are comparable to other reported series of C1-C2 fusion. Additionally, the complications associated with iliac crest graft harvest were avoided by the use of occipital bone graft. Occipital bone appears to be a suitable bone graft substance for fusion of the C1-C2 level.
10678062 [One-stage reimplantation for the salvage of total knee arthroplasty complicated by infect 1997 Aug One-stage reimplantation for the salvage of infected total knee arthroplasty in 8 patients was reviewed at an average follow-up of 20.1 months late infections occurred in 7 (87.5%) patients. The timing of the diagnosis of the infection after knee arthroplasty was of the prosthesis averaged 11.5 months. No one had recurrent infection and pain was relieved significantly in all patients. Our results suggest that one-stage reimplantation is a reasonably reliable procedure for the management of an infected prosthesis. The use of Gentamicin-impregnated bone cement and the Streptomicin bead mixed with Gentamicin improve the success of treating or preventing recurrence of the infection. Early one-stage reimplantation was needed as soon as the deep infection was defined in order to decrease more destruction of the bone.
10403282 Apoptotic chondrocyte death in rheumatoid arthritis. 1999 Jul OBJECTIVE: Recently, chondrocytes were shown to undergo apoptosis by the addition of nitric oxide and by coupling of Fas/Fas ligand in vitro, suggesting the possibility that chondrocytes have an inherent programmed cell death pathway that operates in adult cartilage. Chondrocyte apoptosis was verified in situ in articular cartilage samples from humans with osteoarthritis (OA) and from an animal model of OA. The present study investigates apoptotic chondrocyte death and the expression of Bcl-2 and Fas in rheumatoid arthritis (RA) cartilage. METHODS: Cartilage samples were obtained from 13 RA patients at the time of joint replacement surgery and from 8 normal subjects at autopsy. Apoptotic chondrocytes were observed and counted in hematoxylin and eosin-stained cartilage specimens. Apoptosis was verified by TUNEL, electron microscopy, and DNA ladder assay. Bcl-2 and Fas expression were evaluated by immunohistochemistry. RESULTS: Apoptotic cells were frequently observed in RA cartilage, whereas normal cartilage rarely showed apoptotic cells (3.01% versus 0.15%, respectively), a finding that was further confirmed by TUNEL staining. On electron microscopy, numerous apoptotic cells with typical chromatin condensation were observed in RA cartilage. DNA from RA cartilage also revealed 180-basepair nucleosome ladders on electrophoresis. Bcl-2 expression was significantly lower in RA cartilage than in normal cartilage (23.3% versus 43.1%, respectively), whereas Fas expression was not statistically different. CONCLUSION: Apoptotic chondrocyte death and decreased Bcl-2 expression were verified in RA cartilage. They might provide a novel model system for the research of cartilage breakdown and joint destruction in RA.
9811056 Interleukin-1alpha and tumor necrosis factor alpha synergistically stimulate prostaglandin 1998 Nov OBJECTIVE: Interleukin-11 (IL-11), an IL-6-type cytokine, is thought to be involved in bone resorption via osteoclast differentiation. Here, we characterized the combined effect of IL-1alpha and tumor necrosis factor alpha (TNFalpha), major cytokines in the rheumatoid synovium, on the production of IL-11 by cultured rheumatoid synovial fibroblasts (RSFs). METHODS: The amounts of IL-11, IL-6, and prostaglandin E2 (PGE2) were measured by enzyme-linked immunosorbent assay. IL-11 messenger RNA (mRNA) levels were determined by Northern blotting. Protein expression of cytosolic phospholipase A2 (cPLA2), cyclooxygenase 2 (COX-2), and protein kinase C (PKC) isoforms were determined by Western blotting. RESULTS: IL-1alpha and TNFalpha synergistically stimulated RSFs to produce IL-11 at both the mRNA and protein levels. This synergistic effect was completely inhibited by indomethacin. The inhibition was prevented by PGE2, indicating that the synergistic effect of IL-1alpha and TNFalpha was PGE2-mediated. The cooperative effects of these 2 cytokines were also observed in the production of PGE2 and the expression of 2 regulatory enzymes in PGE2 production, cPLA2 and COX-2. The synergistic induction of IL-11 by IL-1alpha and TNFalpha was completely inhibited by a potent inhibitor of all isoforms of PKC, GF109203X. In contrast, phorbol myristate acetate, which induced a down-regulation of PKC, degrading all PKC isoforms except atypical PKC, did not affect the induction of IL-11. CONCLUSION: These findings suggest that IL-1alpha and TNFalpha synergistically stimulate the production of IL-11 via their effects on PGE2 production in the rheumatoid joint, and that atypical PKC may be another target for down-regulation of IL-11, the bone resorption-associated cytokine.
9292807 The holmium YAG laser in office based arthroscopy of the knee: comparison with standard in 1997 Sep OBJECTIVE: To confirm the feasibility of laser assisted technology in an office based rheumatology practice and to compare selected outcome variables with those of conventional arthroscopic cutting tools. METHODS: A prospective analysis of 70 office based arthroscopies on 70 patients with knee arthritis over an 8 month period. All patients met specific criteria for office based arthroscopy. Thirty-six patients had interventions with conventional cutting tools and 34 patients had interventions with a 40 watt holmium YAG laser. Variables assessed included procedure time, length of recuperative period, and postprocedural pain. RESULTS: Laser assisted arthroscopy was performed in 34 cases without side effects or complications. Patients who received laser treatment had a shorter recuperative period, less postprocedural pain, and fewer hemarthroses than patients treated with conventional methods. CONCLUSION: While recognizing the shortcomings and possible complications associated with laser surgery, we conclude that laser use in an office setting is not only feasible but may in the future be an excellent method for office based arthroscopic treatment of the arthritic knee.
11037892 A cost-effectiveness analysis of treatment options for patients with methotrexate-resistan 2000 Oct OBJECTIVE: Recently, new treatment options for rheumatoid arthritis (RA) patients with an inadequate response to methotrexate (MTX) have become available. Given the wide variability in efficacy and costs among these different treatment options, we sought to determine their cost-effectiveness (CE) in order to guide policy in different cost-constrained settings. METHODS: We performed a CE analysis comparing 6 treatment options for patients with MTX-resistant RA: 1) etanercept + MTX, 2) etanercept monotherapy, 3) cyclosporine + MTX, 4) triple therapy (hydroxychloroquine, sulfasalazine, and MTX), 5) continuation of MTX monotherapy, and 6) no second-line agent. A decision model was used with a time horizon of 6 months. We used 2 measures of effectiveness based on published clinical trial data: the American College of Rheumatology 20% response criteria (ACR 20); and a weighted average of proportions of patients achieving responses of ACR 70, ACR 50, and ACR 20 (ACR 70 weighted response [ACR 70WR]). Incremental CE ratios were calculated as the additional cost per patient achieving either outcome, compared with the next least expensive option. To help interpret CE relative to these RA-specific outcomes, we conducted a separate, "reference" CE analysis of MTX use in MTX-naive RA patients, using the same outcomes. RESULTS: In our reference analysis, MTX therapy for MTX-naive RA cost $1,100 per ACR 20 outcome and $1,500 per ACR 70WR, compared with no second-line agent. In our base-case analysis with either outcome, MTX continuation, cyclosporine + MTX, and etanercept monotherapy cost more, but either were not more efficacious or had a higher incremental CE ratio than the next most expensive option (i.e., they were dominated). Therefore, these options were not cost-effective. The least expensive option, triple therapy, cost 1.3 times more per patient with ACR 20 outcome ($1,500/ACR 20) and 2.1 times more per ACR 70WR ($3,100/ACR 70WR) than MTX therapy for MTX-naive RA. The most efficacious option, the combination of etanercept and MTX, cost 38 times more per patient with ACR 20 outcome ($4,600/ACR 20) and 23 times more per ACR 70WR ($34,800/ACR 70WR) than MTX therapy for MTX-naive RA. Overall, the results of extensive sensitivity analyses did not substantially affect these results. CONCLUSION: Our analysis indicates that if 15 mg/week MTX is cost-effective for achieving ACR 20 or ACR 70WR in MTX-naive RA over a 6-month period, then most likely so is triple therapy in MTX-resistant RA. Whether etanercept + MTX is cost-effective depends on whether $34,800/ACR 70WR (or $42,600/ACR 20) over a 6-month period is considered acceptable.
9368193 Quality of life and lifestyle disruption in euthymic bipolar disorder. 1997 Sep The objective was to assess the extent and pattern of illness intrusiveness, one measure of quality of life, in subjects with bipolar disorder (BD) and to determine whether specific illness variables had influenced the degree of intrusiveness experienced. To compare findings from BD subjects relative to published findings for subjects with chronic medical conditions. The study involved the administration of a self-report assessment tool to euthymic outpatients with BD attending a university based hospital clinic. Of the 155 eligible participants, 112 completed a standardized psychiatric interview (SADS-L) and 87 of these met study criteria for euthymia and were approached to participate in the study. Sixty-eight completed self-report measures were returned. The main outcome measure was the Illness Intrusiveness Rating Scale (IIRS) which was analysed along with a composite measure of life events. It resulted that individuals' with BD experience significant illness intrusiveness into a number of life domains even after controlling for negative life events. Factors such as type of BD, the presence of a depressive episode in the preceding year and current Hamilton depression rating scale score contributed to the total illness intrusiveness. The degree of total illness intrusiveness experienced by individuals with BD was similar to that of subjects with multiple sclerosis and greater than subjects with end stage renal disease and rheumatoid arthritis. It seems apparent that quality of life, as determined by illness intrusiveness, is compromised in subjects with BD even during periods of euthymia. BD is at least as intrusive as several chronic medical conditions. Those with a type II BD report greater impairment in all domains compared with type I. Future research should determine specific psychosocial interventions aimed at reducing the impact of BD.