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ID PMID Title PublicationDate abstract
10325668 Granisetron (Kytril) suppresses methotrexate-induced nausea and vomiting among patients wi 1999 Mar OBJECTIVE: Methotrexate (MTX) is an increasingly popular anti-rheumatic drug with its usefulness limited by toxicity, most commonly gastrointestinal (GI). The aim of the study was to study the effectiveness of the 5-HT3 receptor antagonist granisetron (GR) in the therapy of MTX-induced nausea. METHODS: A single-blind 8 week pilot study with random allocation to either GR 1 mg or prochlorperazine (Stemetil; PCh) 10 mg was undertaken in 13 patients who were taking or had taken MTX for either rheumatoid arthritis (10) or psoriatic arthritis (3). RESULTS: One in six patients treated with PCh completed the 8 week study compared to 7/7 treated with GR. After switching of symptomatic patients, 11 completed the study on GR and median improvement was by two grades (P < 0.001) with a significantly better visual analogue scale score for patient satisfaction compared to PCh. CONCLUSION: Treatment with GR may be useful in establishing and maintaining some patients on MTX where GI toxicity would have precluded such therapy.
9350294 High levels of neutralizing autoantibodies against IL-1 alpha are associated with a better 1997 Oct Neutralizing autoantibodies to interleukin (IL)-1 alpha were detected in a subset of chronic polyarthritis patients characterized by an increased proportion of patients with primary Sjögren's syndrome or self-limiting inflammatory arthritis, diseases with a much better prognosis than rheumatoid arthritis (RA). The evolution of anti-IL-1 alpha antibody levels was followed over 3 years. Incidence and levels were higher in patients with a benign form of polyarthritis. In these patients levels remained stable or increased over the follow-up period. In contrast, incidence and levels were lower and some RA patients became negative. Negative correlations were observed between the levels of anti-IL-1 alpha antibodies and the clinical and biological indices of disease activity. The relative risk factor of developing RA was 12 in the absence of high anti-IL-1 alpha antibody levels and 18.2 when associated with the presence of HLA-DR4. In conclusion, the presence of anti-IL-1 alpha autoantibodies appears to be protective and their detection could represent a marker of good prognosis for destruction.
9631749 Clinical, laboratory and immunogenetic aspects of post-traumatic psoriatic arthritis: a st 1998 May OBJECTIVE: In a previous study we demonstrated that the prevalence of trauma preceding arthritis was higher in patients with psoriatic arthritis (PsA) than in patients with rheumatoid arthritis (RA) or ankylosing spondylitis (AS); of 300 consecutive patients with PsA, 25 (8%) had a history of trauma before (< 3 months) the onset of the disease. The present study was carried out to characterize the clinical, laboratory and immunogenetic profiles of post-traumatic (PT)-PsA. PATIENTS AND METHODS: The clinical and laboratory features of 25 patients with PT-PsA were studied at onset (first 6 months) and after a follow-up period of 1-7 years, and were compared with those of 275 PsA patients without any history of trauma (nonPT-PsA). HLA typing was performed in PT-PsA patients, and synovial fluid (SF) analysis, including interleukin (IL)-1 and IL-6 determinations, was carried out in 12 subjects with PT-PsA and in 32 with nonPT-PsA. RESULTS: No differences were observed between PT-PsA and nonPT-PsA patients with regard to their clinical evolution. ESR (p < 0.0001) and CRP (p = 0.005) were higher in PT-PsA than in nonPT-PsA patients at disease onset but not after follow-up. No differences were found in the other blood indices. SF analysis revealed higher IL-6 levels in PT-PsA than in nonPT-PsA patients (p < 0.0005). CONCLUSION: Our study demonstrates that the prevalence of trauma preceding arthritis is higher in PsA than in RA or AS. Clinical and laboratory findings in patients with PT-PsA differed from those with nonPT-PsA only at disease onset (first six months), however, showing an abrupt clinical presentation and a more acute phase response. This pattern may be related to the higher levels of IL-6 found in the SF of PT-PsA than in nonPT-PsA patients. However, during the follow-up period the two groups became indistinguishable, and no difference was observed between PT-PsA and nonPT-PsA regarding the evolution of the disease.
10972371 Etanercept in the treatment of psoriatic arthritis and psoriasis: a randomised trial. 2000 Jul 29 BACKGROUND: Etanercept, a tumour-necrosis-factor inhibitor, has shown efficacy in the treatment of rheumatoid arthritis. Psoriatic arthritis and psoriasis are disease states in which tumour necrosis factor, a proinflammatory cytokine, is present in increased concentrations in joints and in the skin. Therefore, psoriatic arthritis and psoriasis may be appropriate therapeutic targets for etanercept. METHODS: This randomised, double-blind, placebo-controlled, 12 week study assessed the efficacy and safety of etanercept (25 mg twice-weekly subcutaneous injections) or placebo in 60 patients with psoriatic arthritis and psoriasis. Psoriatic arthritis endpoints included the proportion of patients who met the Psoriatic Arthritis Response Criteria (PsARC) and who met the American College of Rheumatology preliminary criteria for improvement (ACR20). Psoriasis endpoints included improvement in the psoriasis area and severity index (PASI) and improvement in prospectively-identified individual target lesions. FINDINGS: In this 12 week study, 26 (87%) of etanercept-treated patients met the PsARC, compared with seven (23%) of placebo-controlled patients. The ARC20 was achieved by 22 (73%) of etanercept-treated patients compared with four (13%) of placebo-treated patients. Of the 19 patients in each treatment group who could be assessed for psoriasis (> or = 3% body surface area), five (26%) of etanercept-treated patients achieved a 75% improvement in the PASI, compared with none of the placebo-treated patients (p=0.015). The median PASI improvement was 46% in etanercept-treated patients versus 9% in placebo-treated patients; similarly, median target lesion improvements were 50% and 0, respectively. Etanercept was well tolerated. INTERPRETATION: Etanercept offers patients with psoriatic arthritis and psoriasis a new therapeutic option for control of their disease.
10693870 Cyclosporin A prevents the histologic damage of antigen arthritis without inducing fibrosi 2000 Feb OBJECTIVE: To study the effects of cyclosporin A (CSA) in a model of rheumatoid arthritis (RA) and the activation of growth factors related to pannus development at the site of injury. METHODS: Antigen arthritis was induced in the knees of 14 New Zealand rabbits, and the animals were randomized into 2 therapeutic groups: CSA at 10 mg/kg/day and CSA solvent. After 3 weeks of treatment, the rabbits were killed, and synovial tissues were obtained and compared with healthy specimens with regard to histopathologic lesions, deposition of transforming growth factor beta (TGFbeta) and collagens, and messenger RNA expression of platelet-derived growth factor B (PDGF-B) and TGFbeta. The effect of CSA on the expression of TGFbeta and PDGF-B was also examined in cultured synovial cells. RESULTS: CSA administration alleviated the histologic damage and avoided the overdeposition of matrix elements in the injured tissue. It was also able to normalize the enhanced expression of TGFbeta and PDGF-B observed in the untreated rabbits. Despite this modulation found in vivo, CSA up-regulated in a dose-dependent manner the gene expression of both trophic factors by healthy cultured synovial cells. CONCLUSION: The present study shows that continuous administration of CSA prevents the development of chronic synovitis in an experimental model of RA. As reported in other cell types, CSA promoted TGFbeta transcription by synovial cells in vitro, but failed to display a profibrogenic effect in the inflamed environment.
10513491 Effects of an eight-week physical conditioning program on disease signs and symptoms in ch 1999 Feb OBJECTIVE: To investigate the effects of an 8-week, 24-session weight-bearing physical conditioning program on disease signs and symptoms in children with chronic arthritis. METHODS: In a within-subjects, repeated measures design, 25 subjects, ages 8-17 years, with chronic polyarticular juvenile rheumatoid arthritis (JRA), were assessed at study entry, after an 8-week control period, and after an 8-week exercise period, for 1) disease status, based on joint count (JC) and articular severity index (ASI) (sum of scores for joint swelling, pain on motion, tenderness, and limitations of motion); 2) worst pain during the past week, using a 10-cm visual analog scale (VAS), and 3) aerobic endurance, using the 9-minute run-walk test of the Health Related Physical Fitness Test battery. The 60-minute conditioning program included warm-up (10 minutes), low-impact aerobics (25 minutes), strengthening (15 minutes), and cool-down and flexibility exercises (10 minutes). Subjects exercised twice a week at their rheumatology center and once a week at home, using a commercial exercise video-tape supplied by the investigator. RESULTS: Significant improvement was found in the ASI (Friedman analysis of variance [ANOVA]), JC, and 9-minute run-walk test (repeated measures ANOVA) from the pre- to post-exercise tests. Mean VAS pain scores decreased 16% from study entry to the post-exercise test. Statistically significant improvement (reliable change index > 1.96) occurred in 80% of subjects on the ASI and 72% on the JC. CONCLUSION: Children and adolescents with chronic polyarticular JRA can improve their aerobic endurance through participation in weight-bearing physical conditioning programs without disease exacerbation or increased pain, and may achieve decreased joint signs and symptoms through increased physical activity.
9396372 [A case of polymyalgia rheumatica with excessive increase of rheumatoid factor]. 1997 Oct A 76 year-old woman suffered from muscle pain and stiffness of acute onset in her shoulder girdle and pelvic girdle, which were followed by mild left temporal headache and transient arthralgia. Neither joint swelling nor sicca symptom was observed. Laboratory data showed high ESR (128 mm/hr), positive CRP (12.9 mg/dl), increased fibrinogen (485 mg/dl) and high titer of rheumatoid factor (RF) (RAHA x 640). Other autoantibodies examined were negative. Muscle enzymes and electromyogram were within normal limits. Joint X ray didn't reveal the finding suggestive of RA. After the treatment with prednisolone (PSL) 15 mg/day, clinical symptoms and laboratory data improved dramatically. Though she had excessive increase of RF (RAHA x 10240) during therapy, no recurrence of articular symptoms were recognized. She continues to be well with PSL 5 mg/day after 1 year 5 months from onset. As for polymyalgia rheumatica (PMR) followed by RA, the appearance or exacerbation of arthritis corresponding to the elevation of RF occurred in all previously reported 17 cases. Recurrence of arthralgia corresponding to the elevation of RF was not recognized in this case. In addition, Hunder et al reported that PMR with little or no observable joint swelling after several weeks of symptoms is unlikely to develope RA. Therefore, it is speculated that this case in unlikely to develope RA and assessment of arthritis corresponding to the elevation of RF is important to differentiate PMR and elderly-onset RA. This case of PMR is the 5th case with excessive increase of RF in Japan.
10837550 Progress in development of herpes simplex virus gene vectors for treatment of rheumatoid a 1997 Aug 11 Arthritis is presently incurable and poorly treatable, but there are good grounds for expecting gene therapy to improve matters considerably. Although local ex vivo delivery of anti-arthritic genes to the synovial lining of joints has shown considerable promise, intraarticular gene delivery may be desirable. Herpes simplex virus (HSV) may be a viable vector for in vivo transfer of anti-arthritic genes to joints. HSV has the advantages of high infectivity, large carrying capacity and high titer. The large packaging capacity would permit the inclusion of multiple anti-arthritic genes and necessary regulatory elements. Recombinant vectors produced by this laboratory infect synovial cells efficiently, permitting prolonged expression of transgenes in vitro and in vivo without evidence of cytotoxicity. Further improvements to this vector system include taking advantage of an endogenous HSV 'stealthing' gene, ICP47, which interferes with formation of antigen-class I complexes. Inclusion of inducible promoters to appropriately regulate expression of anti-arthritic genes should further improve this system.
17694363 Etodolac in the management of pain: a clinical review of a multipurpose analgesic. 1997 Etodolac is a non-steroidal anti-inflammatory drug with analgesic properties. Its primary anti-inflammatory mechanism of action is through a selective effect on cyclo-oxygenase-2 (COX-2). It is rapidly absorbed after oral administration, and maximum plasma concentration (C(max)) is reached in 1-2 h, with an elimination half-life (t1/2 ) of 6-8 h.Etodolac has been widely applied in the treatment of inflammatory arthritides such as rheumatoid arthritis, ankylosing spondylitis and gout and in osteoarthritis and has been shown to be efficacious and well tolerated.However, etodolac has other applications which rely primarily on its efficacy as an analgesic. In particular, etodolac has been evaluated in the treatment of a variety of different pain states. Etodolac has been observed to be efficacious in the treatment of acute pain following dental extraction, orthopaedic and urological surgery, and episiotomy, as well as in the treatment of pain due to acute sports injuries, primary dysmenorrhoea, tendonitis, bursitis, periarthritis, radiculalgia and low back pain.These studies indicate that etodolac is a multipurpose analgesic with many clinical applications in addition to its use in the treatment of inflammatory and degenerative forms of arthritis.
10955330 Alleles from chromosomes 1 and 3 of NOD mice combine to influence Sjögren's syndrome-like 2000 Aug OBJECTIVE: NOD mice exhibit at least 2 overlapping autoimmune diseases: autoimmune endocrinopathy (Type I, insulin dependent diabetes) and autoimmune exocrinopathy (Sjogren's syndrome, SS). To date, 18 chromosomal regions have been identified that contribute to development of diabetes in NOD mice; however, genetic mapping of similar susceptibility loci for autoimmune exocrinopathy is just beginning. We investigated if these 2 autoimmune diseases share a genetic predisposition. METHODS: Congenic partner strains of NOD and C57BL/6 mice containing defined genetic intervals influencing susceptibility to diabetes (Idd) were screened for histological and biochemical markers for their effect on the development of SS-like disease. Saliva flow rates, protein concentration, amylase activity, and cysteine protease activity were evaluated. RESULTS: In contrast to the nonsusceptible parental C57BL/6 strain, C57BL/6.NOD Idd5 congenic partner strain, containing a genetic region derived from chromosome 1 of the NOD mouse, exhibited pathophysiological characteristics of autoimmune exocrinopathy. Replacement of individual diabetes susceptibility intervals Idd3, Idd5, Idd13, Idd1, and Idd9, as well as a combination of the Idd3, Idd10, and Idd17 intervals, with resistance alleles had little effect on development of autoimmune exocrinopathy. Conversely, NOD mice, in which the chromosome regions containing both Idd5 and Idd3 have been replaced by intervals derived from C57BL mice, exhibit a reduced pathophysiology associated with SS-like autoimmune exocrinopathy. CONCLUSION: Alleles on chromosomes 1 (Idd5) and 3 (Idd3) in combination appear to greatly influence susceptibility and resistance to development of autoimmune exocrinopathy. The association with certain Idd, but not other Idd loci, indicate that genetic overlap is present but probably not inclusive.
10680192 The Chinese anti-inflammatory and immunosuppressive herbal remedy Tripterygium wilfordii H 2000 Feb Various preparations of Tripterygium wilfordii Hook F (TwHF) have been used in the treatment of a number of autoimmune and inflammatory diseases since the 1960s. Accumulated data from the clinical trials suggest efficacy of this treatment in a number of rheumatic diseases, including rheumatoid arthritis and systemic lupus erythematosus. Studies on the relationship of the chemical components of TwHF and its immunosuppressive and anti-inflammatory effects suggest that diterpenoid compounds with epoxide groups account for the therapeutic effects of this herbal remedy. This herbal remedy is therefore a unique and powerful alternative therapy for autoimmune and inflammatory diseases.
11274835 Atlantoaxial joints: patterns of gadolinium enhancement with MR imaging in normal subjects 2001 Jan OBJECTIVE: To evaluate normal patterns of enhancement of signal intensity in and about the atlantoaxial joints following intravenous administration of a gadolinium-containing contrast agent. METHODS AND MATERIAL: Fat-suppressed axial T1 weighted SE images were obtained in 12 patients without evidence of inflammmatory arthritis before and immediately after intravenous administration of a gadolinium-containing contrast agent. Patterns of enhancement of signal intensity in and about the atlantoaxial joints were evaluated qualitatively. RESULTS: Four different MR imaging patterns were observed: no enhancement of signal intensity, enhancement in the form of a single punctate region, enhancement in a confluent pattern, and bandlike enhancement. CONCLUSION: Enhancement occurs around the odontoid process in patients without evidence of rheumatoid arthritis (RA). The dividing line between early synovitis and normal enhancement seems broader than expected. The reasons remain unclear and warant further studies.
11094425 Post-transcriptional regulation of pro-inflammatory gene expression. 2000 The cytokine tumour necrosis factor (TNF)alpha is a vital mediator of the innate immune response, and a pleiotropic regulator of cellular function. Its involvement in rheumatoid arthritis is illustrated by the clinical benefits of TNF alpha blockade. Post-transcriptional regulation (the control of mRNA stability and translation) appears to play a critical role in the regulation of TNF alpha expression by mitogen activated protein kinase signal transduction pathways and by anti-inflammatory agents. The aim of this article is to review some recent advances in our understanding of these processes, and to speculate on mechanisms of regulation of TNF alpha and other pro-inflammatory genes.
10225816 HLA-DRB1 alleles associated with polymyalgia rheumatica in northern Italy: correlation wit 1999 May OBJECTIVE: To examine the association of HLA-DRB1 alleles with polymyalgia rheumatica (PMR) in a Mediterranean country and to explore the role of HLA-DRB1 genes in determining disease severity. METHODS: A five year prospective follow up study of 92 consecutive PMR patients diagnosed by the secondary referral centre of rheumatology of Reggio Emilia, Italy was conducted. HLA-DRB1 alleles were determined in the 92 patients, in 29 DR4 positive rheumatoid arthritis (RA) patients, and in 148 controls from the same geographical area by polymerase chain reaction amplification and oligonucleotide hybridisation. RESULTS: No significant differences were observed in the frequencies of HLA-DRB1 types and in the expression of HLA-DRB 70-74 shared motif between PMR and controls. The frequency of the patients with double dose of epitope was low and not significantly different in PMR and in controls. No significant differences in the distribution of HLA-DR4 subtypes were observed between DR4+ PMR, DR+ RA, and DR4+ controls. Results of the univariate analysis indicated that an erythrocyte sedimentation rate (ESR) at diagnosis > 72 mm 1st h, the presence of HLA-DR1, DR10, rheumatoid epitope, and the type of rheumatoid epitope were significant risk factors associated with relapse/recurrence. Cox proportional hazards modelling identified two variables that independently increased the risk of relapse/recurrence: ESR at diagnosis > 72 mm 1st h (RR=1.5) and type 2 (encoded by a non-DR4 allele) rheumatoid epitope (RR=2.7). CONCLUSION: These data from a Mediterranean country showed no association of rheumatoid epitope with PMR in northern Italian patients. A high ESR at diagnosis and the presence of rheumatoid epitope encoded by a non-DR4 allele are independent valuable markers of disease severity.
10920689 [Rapidly progressed secondary amyloidosis in a patient with Still's disease with gamma-all 2000 Jun A fifteen-year-old boy was admitted to our hospital because of lower abdominal pain, watery diarrhea and mucobloody stool. Two years before admission, he was diagnosed to have Still's disease presenting with polyarthritis, sore throat, remittent fever and typical skin rash. He had been treated with non-steroidal anti-inflammatory agents, oral prednisolone and low-dose methotrexate. Although he was almost free of symptoms during the next two years, serum C-reactive protein (CRP) levels continued to be elevated moderately. He began to complain of lower abdominal pain and loose stool in May 1997 and came down with mucous-bloody diarrhea in June. Laboratory data on admission showed an elevated level of serum CRP (13.9 mg/dl). The biopsy of the stomach, ileum, sigmoid colon and rectum revealed the deposition of amyloid protein of AA type, which confirmed the diagnosis of secondary amyloidosis. The dose of prednisolone was increased and dimethyl sulfoxide per os or rectum was instituted, which improved his gastro-intestinal symptoms to some extent. However, fever, arthritis and diarrhea recurred along with tapered prednisolone dosage. In addition to gastro-intestinal symptoms, arrhythmia and proteinuria appeared. These symptoms were considered to reflect general deposition of amyloid in his body. He is now on immunosuppressive agent and high-dose prednisolone. Several studies report the higher frequency of gamma-allele of SAA 1 gene in the cases of rheumatoid arthritis with AA-amyloidosis than in those without. In the patient presented here, molecular biological analysis revealed that his SAA 1 gene was composed of beta- and gamma-allele. The presence of gamma-allele in his SAA 1 gene might be one of the factors that predisposed him for generalized deposition of amyloid protein in such a short period of time.
11490537 [Follow-up of the patient with spondyloarthropathy]. 1998 Apr Spondylarthropathies consist of several disorders: reactive arthritis, psoriatic arthritis, arthritis associated with inflammatory bowel disease, a subgroup of juvenile chronic arthritis, and ankylosing spondylitis. Their clinical presentation may consist in the following inter-related features: axial involvement, peripheral articular involvement, enthesiopathic lesions, extra-articular disease. The monitoring of these diseases is related more to their clinical presentation than to the precise diagnosis. Modalities for monitoring peripheral arthritis are similar to those of rheumatoid arthritis (essentially based on the number of tender and swollen joints). The modalities of the monitoring of extra-articular features (uveitis, psoriasis,...) are specific to these clinical features and can be categorized in 2 ways: the first one consists in considering the occurrence of the episodes (for example, number of acute anterior uveitis per year), the second one consists in the evaluation of the severity of the clinical features (for example the area of psoriatic skin lesions). Numerous tools have been proposed to evaluate the axial involvement of the disease. The international rheumatologic community (ILAR for International League Against Rheumatism) via specific task force (ASAS for Assessment in Ankylosing Spondylitis) tried to standardize the medical language (at least in clinical research studies) by giving recommendations to evaluate specific domains and within each domain specific tools. Currently, it is generally agreed that pain and functional impairment are the two main domains to consider. For each of these domains, different tools have been proposed (for example the ASFI: Ankylosing Spondylitis Functional Index and the BASFI: Bath Ankylosing Functional Index are both tools proposed to evaluate the functional impairment). The domain "range of motion" is probably one of the most important for long term outcome in clinical research studies and for facilitating the orthopedic indications in daily practice. Finally, radiological tools permitting the evaluation of the structural damage of the disease are available. They take into account the presence and/or the severity of hip and sacroiliac involvement and also the extent of the spinal syndesmophytes. Longitudinal studies are required to evaluate their clinical relevance.
11371660 High in vivo expression of interleukin-17 receptor in synovial endothelial cells and chond 2001 May OBJECTIVE: To evaluate the presence of interleukin-17 (IL-17) and the expression of IL-17 receptor (IL-17R) in joint tissues from subjects with different arthritides. METHODS: Immunohistochemistry was used on frozen synovial and cartilage biopsies to identify cells expressing IL-17 and IL-17R. RESULTS: IL-17 staining was present only in synovial biopsies of rheumatoid arthritis (RA) (seven out of nine cases). IL-17R was expressed by all synovial biopsies evaluated except for three cases of post-traumatic arthritis (PTA). Vascular endothelial cells mainly expressed IL-17R. The percentage of IL-17R(+) vessels was the highest in RA synovium and the lowest in PTA. Chondrocytes from all types of arthritides were negative for IL-17 staining, but expressed IL-17R; the highest percentage of positive chondrocytes was found in seronegative spondylarthritis and the lowest in RA. CONCLUSIONS: IL-17-positive cells are found exclusively in RA. On the other hand, synovial endothelial cells and chondrocytes expressing IL-17R are found in the majority of patients with different types of arthritis. This finding suggests a role for a second ligand for IL-17R, which could be either a different cytokine or a different isoform of IL-17.
10419870 Influence of long term silicone implantation on type II collagen induced arthritis in mice 1999 Aug OBJECTIVES: The use of silicone implants in cosmetic and reconstructive surgery has been implicated in the development of autoimmune connective tissue diseases. Previous investigation of the influence of short-term silicone implantation using an experimental model of rheumatoid arthritis revealed no adverse influence upon disease despite the generation of autoantibodies against silicone bound proteins. This study was designed to examine the influence of long term implantation of different forms of silicone in collagen induced arthritis. METHODS: DBA/1 mice were surgically implanted with silicone elastomers, gel or oil nine months before immunisation with type II collagen emulsified in Freund's incomplete adjuvant. The incidence and severity of arthritis, antibodies to type II collagen, and serum cytokines were assessed and compared with sham implanted mice. Silicone implants were recovered, and autoantibodies to silicone bound proteins evaluated in arthritic and non-arthritic mice. RESULTS: Immunisation with CII/FIA resulted in a 30% arthritis incidence in sham implanted DBA/1 mice. Long term silicone implantation resulted in an increased incidence of arthritis, with a significant increase of 90% arthritis in animals implanted with silicone elastomers. Animals implanted with silicone elastomer also developed foreign body sarcomas during the study. Serum concentrations of interleukin 10 were increased in mice implanted with elastomers and immunised with CII/FIA, while interleukin 5 concentrations were significantly diminished in these mice. The production of autoantibodies to autologous silicone bound proteins, including anti-type I collagen antibody, was also attributed to the implantation of either silicone gel or silicone elastomer in type II collagen immunised animals. CONCLUSIONS: These data suggest that long term silicone implantation results in both the production of autoantibodies to connective tissue antigens and increased susceptibility to an experimental model of autoimmune disease.
9195516 Nested polymerase chain reaction strategy simultaneously targeting DNA sequences of multip 1997 Jun OBJECTIVE: Bacteria play a crucial pathogenetic role in reactive arthritis (ReA) and other forms of spondyloarthropathy (SpA) and in Lyme arthritis. Although there is evidence of local persistence of bacterial antigens no definitive method revealing microbes in peripheral joints has been established. We detected DNA of individual bacteria in synovial material by PCR. Applying molecular technology we screened simultaneously for 8 bacterial genomes in arthritis and sacroiliitis. METHODS: Sacroiliac (SI) biopsy specimens taken from the SI joint of 8 patients with ankylosing spondylitis (AS, n = 5) and undifferentiated SpA (uSpA, n = 3) by computed tomography guided biopsy were investigated for presence of bacterial DNA. Similarly, synovial membrane samples obtained by office arthroscopy from 15 patients with ReA (n = 5), uSpA (n = 3), undifferentiated oligoarthritis (uOligo, n = 3), and rheumatoid arthritis (RA, n = 4) were screened. Nested PCR was performed for DNA of the following bacteria: Chlamydia trachomatis, C. pneumoniae, Yersinia enterocolitica, Salmonella enteritidis, Campylobacter jejuni, Shigella flexneri, Klebsiella pneumoniae, and Borrelia burgdorferi. RESULTS: No bacterial DNA was found in the SI biopsies of patients with uSpA and AS. DNA of B. burgdorferi (n = 2) and C. trachomatis (n = 1) was detected in 3 patients with uOligo, but not in patients with ReA or RA. DNA of other microbes including K. pneumoniae was not found. Patients' mean disease duration was 5.3 years (2 mo-8.4 yrs). CONCLUSION: We found bacterial DNA in peripheral joints of patients with uOligo, while in patients with ReA, AS, and uSpA no bacterial DNA was detected in peripheral or SI joints. The failure to detect bacterial DNA in patients with SpA suggests autoimmune mechanisms operate in later stages of disease.
10653849 The role of alpha(4) and LFA-1 integrins in selectin-independent monocyte and neutrophil m 2000 Feb Monocytes and neutrophils are chronically recruited to joints in rheumatoid arthritis. In the joints of rats with adjuvant arthritis, this is mediated, in part, by selectin-dependent and selectin-independent mechanisms. To define the selectin-independent mechanisms, (51)Cr-labeled blood monocytes, (111)In-labeled neutrophils and function blocking mAb to the selectins and integrins were utilized. Integrins contributed to the selectin-independent monocyte migration to arthritic joints with 58-70% inhibition of this recruitment by anti-alpha(4) or anti-LFA-1 mAb, relative to selectin blockade alone. alpha(4) plus P-selectin blockade was as effective as combined blockade of alpha(4), P-, E- and L-selectin, mediating approximately 83% of the overall monocyte migration to the joints. In contrast, LFA-1 was the predominant selectin-independent mechanism for neutrophil recruitment to the joints. LFA-1 together with P-selectin had essential roles in the talar joint. In dermal inflammation in the arthritic rats, LFA-1 accounted for most (69%) of the selectin-independent monocyte migration to the chemoattractant C5a(desArg) (zymosan-activated serum), whereas LFA-1 and Mac-1 both contributed to selectin-independent neutrophil recruitment to C5a(desArg). alpha(4) integrin and P-selectin in concert mediated monocyte recruitment to lipopolysaccharide and IFN-gamma lesions (81%). Thus: (1) either alpha(4) or LFA-1 can mediate monocyte migration to arthritic joints in the absence of selectin function and alpha(4) together with P-selectin is particularly important; (2) LFA-1 is the predominant mechanism of selectin-independent migration of neutrophils to inflamed joints; and (3) in arthritic rats, selectin-independent migration of monocytes and neutrophils to dermal inflammation is mediated by alpha(4) or LFA-1 or both LFA-1 and Mac-1, depending on the leukocyte type, and inflammatory stimulus.