Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
17207385 Cardiovascular and pupillary autonomic nervous dysfunction in patients with rheumatoid art 2006 Nov OBJECTIVES: Patients with inflammatory diseases often demonstrate autonomic nervous dysfunction. This study was initiated to investigate cardiovascular (CAD) or pupillary autonomic dysfunction (PAD) in patients with rheumatoid arthritis (RA). METHODS: Between 1997 and 1998, 33 RA patients were examined for characteristics, and parameters of CAD and PAD. In a longitudinal part of this study, thirty patients have been re-evaluated 8.3 +/- 0.1 yr later (response rate = 91%). RESULTS: A total of 18 patients (60%) demonstrated either CAD or PAD. The prevalence of CAD was 6/30 (20%) and the prevalence of PAD was 15/30 (50%). Of all cardiovascular tests, the Ewing test demonstrated the worst results (13/30 patients were below the 5th percentile). Similar as in other diseases, several RA patients demonstrated autonomic nervous hyperreflexia with values above the 95 th percentile (relative variation coefficient: 7/30; respiratory sinus arrhythmia measure: 12/30; Valsalva measure: 1/30; Ewing measure: 0/30; latency time of pupillary light reflex: 5/30; maximal pupillary area: 0/30). During the 8-year observation period, 4/30 RA patients died. Non-survivors as compared to survivors had increased heart rate variation in the respiratory arrhythmia test (p= 0.038, hyperreflexia) but largely decreased heart rate variation in the Ewing test (p= 0.009, hyporeflexia). Non-survivors as compared to survivors demonstrated more frequent pupillary autonomic dysfunction (100% vs. 42%, p= 0.035). CONCLUSION: This study demonstrates that CAD and PAD were frequent in patients with RA. Patients with a poor test result in the Ewing test and PAD might have an increased risk of death. This study in RA patients demonstrates similar results as in patients with diabetes mellitus.
16176994 Radiological outcome in rheumatoid arthritis is predicted by presence of antibodies agains 2006 Apr OBJECTIVE: To evaluate the significance of antibodies against cyclic citrullinated peptide (anti-CCP) and rheumatoid factors (RFs), before the onset of rheumatoid arthritis and when presenting as early disease (baseline), for disease activity and progression. METHODS: 93 of a cohort of 138 patients with early rheumatoid arthritis (<12 months of symptoms) had donated blood before symptoms of rheumatoid arthritis (defined as pre-patients) and were identified from among blood donors within the Medical Biobank of northern Sweden. Disease activity (erythrocyte sedimentation rate (ESR), C reactive protein, joint score, global visual analogue scale) and radiological destruction in hands and feet (Larsen score) were assessed at baseline and after two years. Anti-CCP antibodies and RFs were analysed using enzyme immunoassays. HLA shared epitope (SE) alleles (DRB1*0401/0404) were identified. RESULTS: Patients with anti-CCP antibodies before disease onset had significantly higher Larsen score at baseline and after two years. In multiple regression analyses baseline values of anti-CCP/IgA-RF/IgG-RF/IgM-RF, swollen joint count, and Larsen score significantly predicted radiological outcome at two years. In logistic regression analyses, baseline values of anti-CCP antibodies/IgA-RF, therapeutic response at six months, and swollen joint count/ESR significantly predicted radiological progression after two years. The baseline titre of anti-CCP antibodies was higher in patients with radiological progression and decreased significantly in those with response to therapy. SE allele carriage was associated with a positive test for anti-CCP antibodies in pre-patients and in early rheumatoid arthritis. CONCLUSIONS: Presence of anti-CCP antibodies before disease onset is associated with more severe radiological damage. The titre of anti-CCP antibodies is related to disease severity.
19053005 Adalimumab could suppress the activity of non alcoholic steatohepatitis (NASH). 2008 Dec The prevalence of non-alcoholic steatohepatitis (NASH) is increasing. NASH confers an increased risk of liver-related morbidity and mortality with a substantial risk of developing liver cirrhosis. At present, there is no established medical treatment for NASH. The pathogenesis of NASH is incompletely understood. Several lines of evidence suggest that TNF-alpha may be involved in the pathogenesis of NASH by promoting liver inflammation, insulin resistance and hepatocyte apoptosis. Anti-TNF-alpha therapy has not been evaluated for the treatment of NASH. We report here on a patient with NASH who has experienced rapid normalization of liver biochemistry during treatment of an associated rheumatoid arthritis with the humanized anti-TNF-alpha antibody adalimumab. This observation suggests that pilot studies may be warranted to evaluate the role of adalimumab for the treatment of NASH.
18299492 Hematologic malignant neoplasms after drug exposure in rheumatoid arthritis. 2008 Feb 25 BACKGROUND: Rheumatoid arthritis is a severe inflammatory polyarthritis that requires long-term treatment with disease-modifying antirheumatic drugs. There is increasing concern about the influence of rheumatoid arthritis therapy on the risk for hematologic malignant neoplasms. METHODS: We used a case-control design nested in a cohort of 23,810 patients with rheumatoid arthritis assembled from administrative databases covering the population of Quebec, Canada. The study was carried out from January 1, 1980, through December 31, 2003. Case patients having hematologic malignant neoplasms were ascertained from physician billing and hospitalization records; each case patient was matched for age and sex with 10 control subjects. Adjusting for clinical variables and concomitant medications, we used conditional logistic regression to analyze potential associations between disease-modifying antirheumatic drug exposures and risk for hematologic malignant neoplasms. We estimated rate ratios attributable to each disease-modifying antirheumatic drug exposure. RESULTS: During the study, hematologic malignant neoplasms developed in 619 patients, including lymphomas in 346 patients, leukemia in 178 patients, and multiple myelomas in 95 patients. The unadjusted rate ratios for hematologic malignant neoplasms after drug exposures were as follows: methotrexate, 1.18 (95% confidence interval [CI], 0.99-1.40); azathioprine, 1.44 (95% CI, 1.01-2.03); and cyclophosphamide, 2.21 (95% CI, 1.52-3.20). Because biologic agents first appeared in the Régie d'Assurance Maladie du Quebec formulary in 2002, there were few exposures to these drugs. Adjusted estimates suggested that hematologic cancer risk was most elevated after exposure to cyclophosphamide (rate ratio, 1.84; 95% CI, 1.24-2.73). For lymphomas only, the adjusted rate ratio after cyclophosphamide exposure was 2.12 (95% CI, 1.33-3.54). CONCLUSIONS: In this large cohort of patients with rheumatoid arthritis, the greatest relative risk for hematologic malignant neoplasms was noted after use of cyclophosphamide. Assessments of risk related to newer and emerging therapies should carefully consider previous and concomitant medication exposures.
19454108 Rheumatoid arthritis. 2007 Aug 1 INTRODUCTION: Rheumatoid arthritis usually starts as a symmetrical polyarthritis, and its course is marked by flares and remissions. The aims of treatment are to relieve pain and swelling, and to improve function. In addition, disease-modifying antirheumatic drugs (DMARDs) may reduce disease progression. METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of drug treatments in people with rheumatoid arthritis who have not previously received any disease-modifying antirheumatic drug treatment? How do different drug treatments compare in people with rheumatoid arthritis who have either not responded to or are intolerant of first-line disease-modifying antirheumatic drugs? We searched: Medline, Embase, The Cochrane Library and other important databases up to June 2005 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found 62 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. CONCLUSIONS: In this systematic review we present information relating to the effectiveness and safety of the following interventions: adalimumab, anakinra, antimalarial drugs, azathioprine, ciclosporin, corticosteroids, cyclophosphamide, etanercept, infliximab plus methotrexate, leflunomide, methotrexate (alone; or plus sulfasalazine plus hydroxychloroquine), oral gold, parenteral gold, penicillamine, sulfasalazine.
16846525 A cell-cycle independent role for p21 in regulating synovial fibroblast migration in rheum 2006 Rheumatoid arthritis (RA) is characterized by synovial hyperplasia and destruction of cartilage and bone. The fibroblast-like synoviocyte (FLS) population is central to the development of pannus by migrating into cartilage and bone. We demonstrated previously that expression of the cell cycle inhibitor p21 is significantly reduced in RA synovial lining, particularly in the FLS. The aim of this study was to determine whether reduced expression of p21 in FLS could alter the migratory behavior of these cells. FLS were isolated from mice deficient in p21 (p21(-/-)) and were examined with respect to growth and migration. p21(-/-) and wild-type (WT) FLS were compared with respect to migration towards chemoattractants found in RA synovial fluid in the presence and absence of cell cycle inhibitors. Restoration of p21 expression was accomplished using adenoviral infection. As anticipated from the loss of a cell cycle inhibitor, p21(-/-) FLS grow more rapidly than WT FLS. In examining migration towards biologically relevant RA synovial fluid, p21(-/-) FLS display a marked increase (3.1-fold; p < 0.05) in migration compared to WT cells. Moreover, this effect is independent of the cell cycle since chemical inhibitors that block the cell cycle have no effect on migration. In contrast, p21 is required to repress migration as restoration of p21 expression in p21(-/-) FLS reverses this effect. Taken together, these data suggest that p21 plays a novel role in normal FLS, namely to repress migration. Loss of p21 expression that occurs in RA FLS may contribute to excessive invasion and subsequent joint destruction.
17660221 Associations between genetic factors, tobacco smoking and autoantibodies in familial and s 2008 Apr OBJECTIVES: The objective of this study was to investigate the association between genes (HLA-DRB1 and PTPN22) and tobacco smoking, separately as well as combined, and serological markers of rheumatoid arthritis (RA) in a French population with RA. METHODS: 274 patients with RA with half of them belonging to RA multicase families, were genotyped for HLA-DRB1 allele and for PTPN22-1858 polymorphism. IgM rheumatoid factor and anti-cyclic citrullinated peptide (anti-CCP) antibodies were determined by ELISA method. The search for association relied on chi(2) test and odds ratio with 95% confidence interval calculation. The interaction study relied on the departure-from-additivity-based method. RESULTS: The presence of at least one shared epitope (SE) allele was associated with anti-CCP antibodies presence (82.5% vs. 68.4%, p = 0.02), particularly with HLA-DRB1*0401 allele (28.0% vs. 16.4%, p = 0.01). Tobacco exposure was associated with anti-CCP antibodies, but only in presence of SE. A tendency toward an interaction was found between tobacco, the presence of at least one HLA-DRB1*0401 allele and anti-CCP antibodies (attributable proportion due to interaction = +0.24 (-0.21+0.76)). The cumulative dose of cigarette smoking was correlated with anti-CCP antibody titres (r = 0.19, p = 0.04). The presence of both SE and 1858T alleles was associated with a higher, but not significantly different, risk for anti-CCP antibodies presence than for each separately. No association was found between PTPN22-1858T allele and tobacco smoking for autoantibody positivity. CONCLUSIONS: Our findings suggest an association between SE alleles and tobacco smoking for anti-CCP positivity and a tendency toward an interaction between the HLA-DRB1*0401 allele and smoking for anti-CCP positivity in this sample of RA.
18234077 Cartilage preservation by inhibition of Janus kinase 3 in two rodent models of rheumatoid 2008 INTRODUCTION: CP-690550 is a small molecule inhibitor of Janus kinase 3 (JAK3), a critical enzyme in the signaling pathway of multiple cytokines (interleukin (IL)-2, -7, -15 and -21) that are important in various T cell functions including development, activation and homeostasis. The purpose of this study was to evaluate CP-690550 in murine collagen-induced (CIA) and rat adjuvant-induced (AA) models of rheumatoid arthritis (RA). METHODS: CIA and AA were induced using standard protocols and animals received the JAK3 inhibitor via osmotic mini-pump infusion at doses ranging from 1.5-15 mg/kg/day following disease induction. Arthritis was assessed by clinical scores in the CIA models and paw swelling monitored using a plethysmometer in the AA model until study conclusion, at which time animals were killed and evaluated histologically. RESULTS: CP-690550 dose-dependently decreased endpoints of disease in both RA models with greater than 90% reduction observed at the highest administered dose. An approximate ED50 of approximately 1.5 mg/kg/day was determined for the compound based upon disease endpoints in both RA models examined and corresponds to CP-690550 serum levels of 5.8 ng/ml in mice (day 28) and 24 ng/ml in rats (day 24). The compound also reduced inflammatory cell influx and joint damage as measured histologically. Animals receiving a CP-690550 dose of 15 mg/k/d showed no histological evidence of disease. CONCLUSION: The efficacy observed with CP-690550 in CIA and AA suggests JAK3 inhibition may represent a novel therapeutic target for the treatment of RA.
18462359 Comparative histopathological analysis between tenosynovitis and joint synovitis in rheuma 2008 Jun AIMS: To clarify the histological and biological features of tenosynovitis accompanying rheumatoid arthritis (RA). METHODS AND RESULTS: Synovial tissue was obtained from the wrist joint and extensor tendon of the digits of six RA patients and the sections were examined by haematoxylin and eosin staining and immunohistochemical analysis. RA tenosynovitis exhibited the typical histological features of RA joint synovitis, including hyperplasia of the synovial lining and infiltration of leucocytes, largely CD4+ T cells and CD68+ macrophages. Notably, there was a significant correlation in the number of CD4+ T cells and CD68+ macrophages between the tenosynovium and joint synovium in each individual. Real-time reverse transcriptase-polymerase chain reaction analysis revealed similar mRNA expression patterns of various inflammatory mediators in tenosynovitis and joint synovitis. It was also observed that synovial fibroblasts isolated from the tenosynovium behaved in a manner similar to those isolated from the joint synovium with regard to proliferation and the production of inflammatory mediators. CONCLUSIONS: The histopathological features of RA tenosynovitis were indistinguishable from those of joint synovitis. Therefore, it is suggested that the ongoing inflammation is driven by similar mechanisms in the tenosynovium and joint synovium and that RA is probably a tissue-specific disease which targets systemic synovial tissues.
18577108 Novel recombinant congenic mouse strain developing arthritis with enthesopathy. 2008 Jul Based on the hypothesis that the complex pathological and immunological manifestations of rheumatoid arthritis (RA) and the related diseases are under the control of multiple gene loci with allelic polymorphism, a recombinant congenic mouse strain was prepared between an MRL/Mp-lpr/lpr (MRL/lpr) strain, which develops arthritis resembling RA, and a non-arthritic strain C3H/HeJ-lpr/lpr (C3H/lpr). In MRL/lpr x (MRL/lpr x C3H/lpr) F1 mice, the mice developing severe arthritis were selected based on joint swelling to further continue intercrosses, and then an McH-lpr/lpr-RA1 (McH/lpr-RA1) strain was established and its histopathological phenotypes of joints and autoimmune traits were analyzed. Arthritis in McH/lpr-RA1 mice developed at a higher incidence by 20 weeks of age, compared with that in the MRL/lpr mice, who had severe synovitis (ankle, 60.3%; knee, 65.1%), and also fibrous and fibrocartilaginous lesions of articular ligamenta resembling enthesopathy (ankle, 79.4%; knee, 38.1%), resulting in ankylosis. The lymphoproliferative disorder was less, and serum levels of IgG and IgG autoantibodies including anti-dsDNA and rheumatoid factor were lower than those of both MRL/lpr and C3H/lpr strains. McH/lpr-RA1 mice may provide a new insight into the study of RA regarding the common genomic spectrum of seronegative RA and enthesopathy.
17696276 Gold therapy in women planning pregnancy: outcomes in one center. 2007 Sep OBJECTIVE: To review the experience and outcome of pregnancies in women taking gold while planning pregnancy. METHODS: We undertook a chart review of patients attending for gold injection and monitoring between January 1992 and April 2006. For women who became pregnant while being followed taking gold therapy, we extracted demographic, treatment, and disease activity data, information regarding pregnancy complications, outcome, and postpartum course. For details missing from the clinic records, patients were interviewed by the clinic nurse. RESULTS: Fourteen women experienced 20 pregnancies while being followed in the gold monitoring clinic. Mean age at the time of conception was 34.5 years (range 24-41), disease duration 8.5 years (1-16). Rheumatoid factor was positive in 9 of 14 women. Duration taking gold prior to conception was < 12 months in 7 pregnancies, 13-24 months in 4, 25-34 months in 2, and 2-10 years in 7 pregnancies. Four women continued taking gold until delivery. The rest of the women discontinued gold when they knew they were pregnant, with the exception of one who held her gold 4 weeks prior to conception. There were 5 spontaneous abortions in the first trimester; included were 2 spontaneous abortions in a woman with known Robertsonian chromosomal translocation. Sixteen babies were healthy including a pair of twins. One baby was born with weakness of one extraocular muscle requiring surgery; one had blocked tear ducts at birth. Rheumatoid arthritis (RA) flared during 3/15 completed pregnancies and postpartum and post-spontaneous abortion in 18/20 pregnancies. CONCLUSION: Our clinic experience and the published literature support the current practice that in patients with RA, gold may still be considered a treatment option in women planning pregnancy.
17963166 Expression of BAFF and BAFF-R in the synovial tissue of patients with rheumatoid arthritis 2007 Sep OBJECTIVE: The elevated expression of B-cell-activating factor belonging to the TNF family (BAFF) is associated with systemic autoimmune disease, including rheumatoid arthritis (RA). The present study was undertaken to determine the distribution of BAFF and its receptor BAFF-R in the cells residing in the rheumatoid synovium. METHODS: The expression of BAFF and BAFF-R in synovial tissues obtained from 12 RA patients was examined by immunohistochemistry and flow cytometry. The mRNA expression of these molecules was determined by reverse transcriptase polymerase chain reaction (RT-PCR). Soluble BAFF levels were measured with an enzyme-linked immunosorbent assay (ELISA). Fibroblast-like synoviocytes (FLS) purified from the RA (RA-FLS) were co-cultured with peripheral B cells. The degree of apoptosis in the B cells was measured to assess the effects on the viability of the B cells. RESULTS: The RA synovium showed focal or diffuse infiltration of mononuclear cells (MNCs), and one specimen showed germinal centre (GC)-like structures. Synovial sublining cells, but not lining cells, expressed BAFF. These sublining cells were negative for BAFF-R. BAFF and BAFF-R were expressed in B and T cells extracted from the RA synovium. Notably, RA-FLS spontaneously expressed cytoplasmic BAFF after 4-6 passages; however, they did not express BAFF or BAFF-R on their cell surface. RA-FLS could support the survival of B cells by preventing their apoptosis, but its effect on B cells might not be BAFF dependent. CONCLUSIONS: BAFF and BAFF-R are widely expressed in the RA synovium. The cells residing in the RA synovium might affect each other through BAFF.
16979122 Influence of leflunomide on gastrointestinal Candida albicans infection induced in naive a 2006 Nov Mucosal Candida albicans infection in immunocompromised individuals being treated with recently advanced drugs can progress to systemic disease. One such medication applied in patients with rheumatoid arthritis is leflunomide. The object of the present study was to investigate the effect of leflunomide on a model of gastrointestinal (g.i.) C. albicans infection induced in naïve or arthritic mice and on the host resistance to systemic re-infection. Newborn mice were orally inoculated with 1 x 10(5) colony forming units (CFU) of C. albicans and at age of 5 weeks they were treated with 5 mg/kg or 20 mg/kg of leflunomide for 10 consecutive days. Both doses elevated the yeast colonization of the stomach, without the dissemination into the internal organs. This was in parallel with the enhanced delayed type hypersensitivity (DTH) reaction to the yeast. Contrary to that, leflunomide caused a shift to Th2 reactivity by prevalence of IL-4 to IFN-gamma and a suppression of anti-Candida antibody synthesis by a higher dose. It might be supposed that infection increased autoimmune response in arthritic mice, according to stimulated DTH reaction to collagen. The administration of leflunomide during the simultaneous development of infection and arthritis diminished anti-Candida and anti-collagen antibody synthesis compared to untreated infected arthritic mice. The improved survival of arthritic infected animals against severe systemic re-infection was not changed after administration of leflunomide to re-infected arthritic mice. We can conclude that although leflunomide influenced cytokine secretion and suppressed anti-Candida antibody production it neither provokes a progression from gastrointestinal to systemic C. albicans infection nor increases the susceptibility to severe C. albicans re-infection of arthritic mice.
17951655 Preparation of mononuclear cells from synovial tissue. 2007 In rheumatoid arthritis (RA), the synovium represents the predominant site of inflammation and joint destruction and is regarded as the key organ involved in disease pathogenesis. It has been studied in different ways over the last 30 yr, yielding information about the mechanisms involved in disease and remains the tool most proximal to understanding the pathogenesis of RA. This chapter outlines how both histological and in vitro studies of dissociated tissue played key roles in the development of biological anti-TNF-alpha therapy and provides detailed protocols used routinely in the laboratory to facilitate studies of RA synovium and its composite cell populations.
16581463 Arthroscopic synovectomy of the knee joint in rheumatoid arthritis: surgical steps for com 2006 Apr For successful arthroscopic total synovectomy in rheumatoid arthritis of the knee, proper sequential steps are required. First, we resect hypertrophied synovial villi on the intercondylar notch to make a gateway for the posterior compartments. We also perform synovectomy at the posterolateral chamber because of the narrower space of the chamber than that of the posteromedial chamber and the intra-articular crowding due to swollen synovial villi with the passage of operation time. Special care should be taken not to overlook both posterior back corners and roofs, which cannot be seen through the transnotch view, even with a 70 degrees arthroscope. The posterior back corners and roofs can be visualized by using the trans-septal approach technique. In this approach, we prefer to perforate the posterior septum in the posterolateral-to-posteromedial direction to avoid damaging the neurovascular structures because the structures are located just behind and lateral to the midline septum and the posteromedial capsule bulges a bit more posteriorly than the posterolateral capsule. Attention is then directed to the medial, lateral, and suprapatellar compartments, and finally the retropatellar compartment. Our surgical steps are safe and effective for complete synovectomy of the rheumatoid arthritic knee joint and other synovial disorders.
17067220 [Prosthetic knee infection caused by Listeria monocytogenes in a woman with rheumatoid art 2006 Jun Listeria are gram-positive bacilli that can be isolated from soil and in the normal fecal flora of many mammals. It is a uncommon pathogen in the general population, but immunocompromised individuals can develop several focal infections, most notably meningoencephalitis and sepsis. Nevertheless, infectious arthritis caused by Listeria monocytogenes is a exceptional event. We report a new case of prosthetic knee arthritis due to Listeria in a woman with seropositive rheumatoid arthritis and Waldenström s macroglobulinemia receiving prednisone and methotrexate. In addition, we review the literature on listeria joint infections.
16583421 Different patterns of illness-related interaction in couples coping with rheumatoid arthri 2006 Apr 15 OBJECTIVE: To learn more about the effect of rheumatoid arthritis (RA) on couples' relationships and how couples manage the illness within their dyad. METHODS: Eight women with RA (ages 31-60 years) and their partners, and 4 men with RA (ages 43-75 years) and their partners were recruited from the rheumatology case load of a hospital in the UK. Interpretative phenomenologic analysis was used for data collection and analysis. During semistructured interviews, couples were asked about the effect of RA on their lives and relationship. RESULTS: This study found clear differences in the way couples managed the illness of one partner and in the nature of their illness-related interactions. Based on these differences, the couples were allocated to 1 of 3 groups: the shared illness management group (SIM), the ill partner in charge group (IPIC), or the conflict over management group (COM). In the SIM group, both partners attended appointments and shared decisions about illness management. In the IPIC group, the ill person claimed and was conceded the right to make autonomous decisions about illness management. In the COM group, the well partner was dissatisfied with the way the ill person was managing the illness, and conflict resulted. CONCLUSION: Heterogeneity exists in the intradyad management of RA. Identifying each couple's style of illness management could make medical consultations and education programs more responsive to the needs and preferences of patients and their partners. Dissatisfaction of either partner with illness management and resulting conflict could be addressed, with benefits for both partners and possible improvement in disease management.
17343585 Trichosporon inkin subcutaneous infection in a rheumatoid arthritis patient. 2007 Mar A 74-year-old woman presented with painful ulcerative nodules on the left forearm. She had received systemic steroid therapy for rheumatoid arthritis for several years. On physical examination, there were four hemorrhagic ulcerative nodules with a linear distribution on the left forearm (Fig. 1A). These nodules had developed over the course of 2 months, and the number of lesions had increased despite systemic antibiotic therapy. There was no sign of systemic dissemination of the disease. Biopsy of a nodule demonstrated suppurative granulomatous infiltration (Fig. 1B); the hyphae stained positive with periodic acid-Schiff (data is not shown) and Gomori-methenamine silver stains in the dermis (Fig. 1C). The biopsy specimen was cultured in Sabouraud's dextrose agar supplemented with cycloheximide with incubation at 26 degrees C. A yeast-like creamy colony grew in 1 week. The colony became yellowish gray in color and the surface folded radially after 4 weeks of incubation (Fig. 2A). Microscopic examination revealed arthroconidia and blastoconidia (Fig. 2B), and urease activity was positive. The fungus was identified as Trichosporon beigelii by yeast biochemical card (YBC, Biomerieux Vitek, Inc., Hazelwood, MO, USA). The sequences of rDNA obtained from the colony were amplified using polymerase chain reaction (PCR) primer, analyzing the sequences of the 5.8S and 28S rDNA regions for the genetic identification of the Trichosporon species. The sequences of the PCR product matched the corresponding sequences of the T. inkin strain with 99% accuracy (Fig. 2C). The patient was given oral itraconazole for 8 weeks with good clinical results.
16510808 Long-term results of the modified Hoffman procedure in the rheumatoid forefoot. Surgical t 2006 Mar BACKGROUND: Rheumatoid arthritis commonly affects the forefoot, causing metatarsalgia, hallux valgus, and deformities of the lesser toes. Various types of surgical correction have been described, including resection of the lesser-toe metatarsal heads coupled with arthrodesis of the great toe, resection arthroplasty of the proximal phalanx or metatarsal head, and metatarsal osteotomy. We report the results at an average of five and a half years following thirty-seven consecutive forefoot arthroplasties performed in twenty patients by one surgeon using a technique involving resection of all five metatarsal heads. METHODS: All patients were treated with the same technique of resection of all five metatarsal heads through three dorsal incisions. All surviving patients were asked to return for follow-up, which included subjective assessment (with use of visual analogue pain scores, AOFAS [American Orthopaedic Foot and Ankle Society] foot scores, and SF-12 [Short Form-12] mental and physical disability scores), physical examination, and radiographic evaluation. RESULTS: All results were satisfactory to excellent in the short term (six weeks postoperatively), and no patient sought additional surgical treatment for the feet. A superficial infection subsequently developed in two feet, and two feet had delayed wound-healing. At an average of 64.9 months postoperatively, the average AOFAS forefoot score was 64.5 points and the average hallux valgus angle was 22.3 degrees. There were no reoperations. CONCLUSIONS: Resection of all five metatarsal heads in patients with metatarsalgia and hallux valgus associated with rheumatoid arthritis can be a safe procedure that provides reasonable, if rarely complete, relief of symptoms.
18388520 Innovative treatment strategies for patients with rheumatoid arthritis. 2008 May PURPOSE OF REVIEW: The present review provides an update on novel treatment strategies striving for remission in patients with recent onset of rheumatoid arthritis. RECENT FINDINGS: As early treatment is crucial to achieve optimal results, identifying patients with rheumatoid arthritis early is imperative to achieve clinical remission. Patients with early arthritis who will progress to rheumatoid arthritis can be identified, and treating these patients can postpone the diagnosis of rheumatoid arthritis and retard the progression of structural damage. The best way to achieve remission is by adjusting treatments at regular intervals using predetermined response criteria. Specific treatments to rapidly induce remission include disease modifying antirheumatic drugs combinations, especially combined with glucocorticoids or tumor necrosis factor antagonists. The prediction of joint damage progression, or the response to specific drugs is not yet accurately possible. The early institution of tumor necrosis factor antagonists followed by discontinuation leads to sustained clinical benefit. SUMMARY: Early treatment of patients with rheumatoid arthritis with strategies aiming at remission results in the best outcomes. Until the prediction of a severe disease course and treatment response becomes possible, a promising strategy would be to rapidly induce remission using an effective combination of drugs followed by tapering and discontinuation. Tumor necrosis factor antagonists have proven to be highly effective in this approach.