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ID PMID Title PublicationDate abstract
11000325 Primary and secondary Sjögren's syndrome in children--a comparative study. 2000 Sep Sjögren's syndrome is a chronic inflammatory systemic autoimmune disease mainly affecting the exocrine and, particularly, the salivary and lacrimal glands. The condition usually occurs in adults. In 1994, the criteria for this syndrome were redefined in a multicenter European study. In children, Sjögren's syndrome is a rare and probably underdiagnosed disease. To date, Sjögren's syndrome in children has only been described in case reports and in the comparative presentation of various study results. So far, no study of a comparative classification into primary and secondary Sjögren's syndrome has been carried out in a patient population of any size. Sjögren's syndrome should be considered in the differential diagnosis of children with recurrent parotitis, keratoconjunctivitis sicca, or pronounced and early tooth decay associated with xerostomia. In this study of 23 children and adolescents under the age of 16 with the clinical symptoms and laboratory findings of Sjögren's syndrome, we differentiate between primary and secondary Sjögren's syndrome. The value of the individual methods of assessing the oral and the ophthalmological components and the manifestation of the underlying rheumatic condition are discussed on the basis of the EULAR criteria. The EULAR diagnostic criteria are of limited applicability in children because reliable anamnestic data are frequently lacking. Another problem in diagnosing Sjögren's syndrome is the short-term detection of serological alterations and clinical symptoms. Even if young patients do not completely fulfill the required criteria, Sjögren's syndrome can be assumed or confirmed in the presence of positive testing for oral and ocular manifestations and recurrent salivary gland enlargement.
10381486 Clinical follow up study of 87 patients with sicca symptoms (dryness of eyes or mouth, or 1999 Jul OBJECTIVE: To assess the prognosis of patients with sicca symptoms and to identify the clinical and immunological factors that most sensitively predict the later development of primary Sjögren's syndrome (SS) or other connective tissue diseases. METHODS: Eighty seven patients (72 female, 15 male) with sicca symptoms were re-evaluated after a median follow up time of 11 years (range 8-17). The clinical examination included ophthalmological examination (Schirmer's test, break up time and Rose-Bengal staining). Labial salivary gland biopsy was performed and histological findings graded according to the Chisholm-Mason scale. The immunoserological tests included determination of rheumatoid factor (RF), antinuclear antibodies (ANA), anti-extractable nuclear antigen-antibodies (ENA), serum immunoglobulins IgA, IgG, and IgM, and serum beta2-microglobulin (beta2m). RESULTS: At follow up 31 patients (36%) fulfilled modified Californian criteria (salivary flow measurements were not performed and Chisholm-Mason grades 3-4 were regarded as diagnostic histological findings) for possible or definite SS. Likewise, a significant progression of the histological findings was observed. Labial salivary gland re-biopsy was performed in 42 patients with grade 0-2 findings at baseline, progression to grades 3-4 being observed in 21 (50%) at follow up. The patients who later developed SS were at baseline significantly older (mean (SD) 52 (9) v 44 (14) years, p
10092062 Expression of CD40/CD40 ligand and Bcl-2 family proteins in labial salivary glands of pati 1999 Mar Lymphocytes infiltrating the salivary glands of patients with Sjögren's syndrome (SS) are activated and resist apoptosis. We determined the role of interactions between CD40 and CD40 ligand (CD40L) in these infiltrating lymphocytes on B-cell differentiation and expression of Bcl-2 family proteins. Ten human T-cell leukemia/lymphoma virus-I (HTLV-I)-seronegative and eight HTLV-I-seropositive SS patients were examined in the present study. Immunohistochemistry was performed to examine the expression of CD3, CD20, PCA-1, CD40, CD40L, Bcl-2, Bax, and Bcl-x on T and B lymphocytes infiltrating labial salivary glands of SS patients. We also examined the expression of CD40 and CD40L on peripheral blood lymphocytes of the same patients by using flow cytometry. CD40L was not expressed on peripheral blood lymphocytes of SS patients. Peripheral blood B cells but not T cells expressed CD40. In contrast, >50% of mononuclear cells, including T and B cells infiltrating the glands, expressed CD40. In addition, a clear expression of CD40L in both infiltrating T cells and B cells, and that of PCA-1, was also demonstrated. Surprisingly, the expression of Bcl-2 and Bcl-x was colocalized with that of CD40 determined by mirror section technique. Bcl-x was also abundantly expressed on infiltrating mononuclear cells, but, Bax expression was relatively less than that of Bcl-2 or Bcl-x. The expression of the above molecules was not different between HTLV-I-seronegative and HTLV-I-seropositive SS patients. Our results indicate that CD40/CD40L pathways could be augmented in salivary glands of SS patients, inducing B-cell differentiation to PCA-1 + plasma cells. Immunohistochemical analysis also suggests that signaling through CD40 by means of CD40L increases the expression of Bcl-2 as well as Bcl-x in infiltrating lymphocytes, providing the resistance against apoptosis. Our findings were commonly observed in SS patients irrespective of HTLV-I seropositivity.
11527804 New coupled-particle light-scattering assay for detection of Ro/SSA (52 and 60 kilodaltons 2001 Sep The diagnostic and analytical performance of the coupled-particle light-scattering assay in detecting anti-Ro/SSA autoantibodies (the 60-kDa [Ro60] and the 52-kDa [Ro52] antibodies) and anti-La/SSB autoantibodies was evaluated. The antigens were obtained by recombinant DNA procedures to include the most immunogenic epitopes for each protein by using a prokaryotic expression system. Serum samples from 151 patients with connective tissue diseases and 52 control subjects (including patients with viral infections, patients with Lyme disease, and healthy subjects) were studied. Sensitivities for detection of anti-Ro/SSA and anti-La/SSB were 88.2 and 95.2%, respectively; specificities were 97.6 and 98.1%, respectively. The intra-assay coefficient of variation (CV) ranged from 4.3 to 10.9% for anti-Ro/SSA and from 2.8 to 12.5% for anti-La/SSB; interassay CVs ranged from 6.5 to 13.2% and from 8.2 to 14.5%, respectively. Among the anti-Ro/SSA-positive samples, Ro60 was recognized by 66% of the test sera and Ro52 was recognized by 95% of the test sera. Thirty-four percent of the Ro/SSA-positive sera were reactive only with the Ro52 antigen, indicating that anti-Ro52 is the most common antibody specificity recognized by anti-Ro/SSA autoantibodies. No differences were found between the prevalences of anti-Ro60 and anti-Ro52 in relation to systemic lupus erythematosus or Sjögren's syndrome. The results of the present study indicate that this new immunoassay is an efficient diagnostic tool for the detection of anti-Ro/SSA and anti-La/SSB antibodies in patients with autoimmune disorders.
11480812 Cytokine concentrations in stimulated whole saliva among patients with primary Sjögren's 2001 Jun Sjögren's syndrome is an autoimmune disorder which causes diminished salivary flow due to autoimmune sialoadenitis. This decrease in saliva flow is the result of inflammation and atrophy of the salivary glands. Most treatment regimens are palliative in nature, but treatment with interferon (IFN) holds promise for Sjögren's syndrome sufferers. Several studies have investigated cytokine concentrations in the salivary glandular tissues from Sjögren's syndrome patients; however, there is little information concerning cytokine expression in saliva. This is especially true with respect to treatment modalities and their effects on local cytokines. A clinical study was conducted to determine salivary interleukin (IL)-6, IFN, and IL-2, concentrations among subjects diagnosed with primary and secondary Sjögren's syndrome and a healthy control group. The primary Sjögren's syndrome showed significantly higher salivary IL-2 and salivary IL-6 than the control and secondary Sjögren's groups. There were no between group differences for salivary IFN concentrations. In addition, the study assessed salivary IL-6, IFN, and IL-2 concentrations among 18 Sjögren's syndrome patients before and after administration of IFN via the oral mucosal route. The results of the study showed that the mean values for the pre- and post-treatment groups for stimulated whole saliva flow rates were 3.15 and 3.74 ml/5 min, respectively. The post-treatment group exhibited a 16.8% increase in stimulated whole saliva flow rates. The salivary IL-6 concentration was 53.3% lower for the post-treatment group (17.79) as compared to the baseline value (33.35). The values for salivary IFN and salivary total protein were virtually unchanged from their baseline values. Salivary IL-2 values, however, were 50% lower in the post-treatment group (3.07) when compared to their respective baseline values (6.10). The results of this study suggest that healthy individuals exhibit lower salivary IL-2 and IL-6 as compared to individuals suffering from primary and secondary Sjögren's syndrome. The results also suggest that administration of IFN via the oral mucosal route may increase salivary flow rates and depress certain cytokines (IL-2, IL-6) associated with inflammatory destruction of salivary glandular tissues in Sjögren's syndrome patients.
11028851 Sjögren's syndrome, cavitating lung disease and high sustained levels of antibodies to se 2000 A case is described involving Sjögren's syndrome, high sustained levels of antibodies to serine proteinase 3, and cavitating lung disease. Possible diagnoses accounting for this unusual combination include a novel association of Sjögren's syndrome and Wegener's granulomatosis (suggested by the high and sustained levels of antibodies to serine proteinase 3) or a rare presentation of bronchiolitis obliterans organising pneumonia. Identification of the true nature of the patients illness facilitated more active management and a swift resolution of the clinical problem.
11474377 [RS3PE syndrome: an acute edematous polyarthritis of the elderly with variable prognosis]. 2001 Jun The RS3PE syndrome or subacute edematous polyarthritis of the elderly remains a doubtful entity. We report three cases that exhibited different courses: complete recovery, definite rheumatoid polyarthritis, and chronicity as a sign of myelodysplasic disease. These three different courses raise the question of whether RS3PE is a disease or a syndrome. Actually, the use of the term RS3PE syndrome should be restricted to cases with a favorable outcome. Definitive diagnosis thus cannot be reached before complete recovery.
11434467 Capillaroscopic findings in erosive and nodal osteoarthritis of the hands. 2001 Osteoarthritis of the hands is a very common disease that can present a large number of different clinic pictures, such as nodal (NOA) and erosive (EOA) forms. EOA in particular is a rare subset of hand osteoarthritis characterised by faster destructive changes involving the distal interphalangeal (DIP) and proximal interphalangeal (PIP) joints. In the early stages of the disease the differential diagnosis from other arthritides, such as rheumatoid or seronegative arthritis, may pose a challenge. Nailfold capillaroscopy is a non-invasive technique that allows the in vivo study of the microvascular environment. In this study the authors have compared the capillaroscopic microvascular patterns in 56 patients with EOA, in 46 patients with NOA, and in 50 normal controls. The abnormalities that could be found in EOA patients were similar to those described by some authors in patients with psoriatic arthritis. The authors discuss the significance of these abnormalities and the possible relationship between EOA and psoriatic arthritis.
18465584 Thalidomide Celgene Corp. 1998 Aug Thalidomide, in development by Celgene, inhibits the effects of elevated TNFalpha and may consequently be of use in a range of diseases including cachexia, bacterial meningitis, rheumatoid arthritis, septic shock, AIDS, tuberculosis, multiple sclerosis, ulcerative colitis, graft-versus-host disease and systemic lupus erythematosus. In July 1998, Celgene received clearance from the US FDA to market and sell Thalomid (thalidomide) for the treatment of erythema nodosum leprosum (a severe and debilitating condition associated with leprosy) [291919], following a recommendation for approval by the FDA advisory committee in September 1997 [261846,263970]. In that same month, Celgene filed an IND for the treatment of the chronic autoimmune disorders Behcet's disease, and aphthosis [264366]. The trial will be conducted by investigators at the Mayo Clinic and Bowman Gray School of Medicine. It will be divided into two phases, the first phase lasting 4 weeks in which patients will receive 100 mg thalidomide or placebo, and a second open-label phase which will call back all patients to receive the same dose of thalidomide over a 24-week period. It will be determined whether the drug significantly reduces existing ulcerations and inhibits the formation of new lesions. Positive results of a National Institute of Allergy and Infectious Diseases trial for aphthous ulceration of the mouth in HIV-infected patients prompted Celgene to commence a pivotal trial for the same indication. A total of 84 patients will be randomized to 100 mg, 200 mg or 400 mg thalidomide/day for 4 weeks. Patients achieving a full response after 4 weeks will be re-randomized on 100 mg thalidomide or placebo for up to another year [248356]. The company has also completed the pivotal phase III trial for AIDS-related cachexia [225437]. Results from a pivotal phase II/III trial showed that the drug significantly increased body weight in AIDS patients, but also increased viral load initially. A total of 99 patients, who had lost more than 10% of their body weight due to HIV infection, received either 100 or 200 mg/day of thalidomide or placebo orally for 8 weeks. Although there was a significant increase in body weight associated with the 100 mg dose (p = 0.025), there was no difference in body weight changes between patients treated with 200 mg doses and those on placebo. There was a 55% dropout rate at the higher dose due to side-effects such as somnolence, rash, neutropenia, neuropathy and dizziness. Viral load was significantly increased after 4 weeks of treatment. However, there was no further increase in viral load at 8 weeks, and patients were not receiving triple combination antiviral therapy [243943]. In April 1996, Celgene initiated a phase II trial of thalidomide in London for the treatment of chronic intractable diarrhea in HIV positive patients. The double-blind, placebo-controlled trial will involve up to 120 patients, aged 18 to 65 inclusive, at three centers for 28 days of therapy; those on drugs will be orally dosed with 100 mg of thalidomide daily at bedtime. The primary endpoint is reduction in the occurrence of diarrhea [205006,206218]. The trial will be conducted in the US, the UK and Mexico [210069]. The company expanded its clinical trial program in June 1996, for use of thalidomide in graft versus host disease and AIDS complications, such as debilitating ulcers of the digestive system [212461]. A phase II trial for the treatment of cachexia in cancer patients was carried out at St George's Hospital, London. Ten patients received thalidomide (100 mg) orally for 8 weeks and ten received placebo. The study was structured to determine the ability of thalidomide to reduce or stabilize the symptoms of cachexia. Quality of life and levels of disease markers will also be assessed. Results showed that after a 3-week treatment period, patients who received thalidomide gained an average 4.5% in overall body weight versus 0.9% with placebo [190161]. Results from a 65 patient multicenter phase II/III trial for cachexia are still awaited [221227]. Celgene is also conducting a double-blind, placebo-controlled pivotal trial for the treatment of rheumatoid arthritis at New York University's Hospital of Joint Diseases. Levels of TNFalpha are increased in patients with rheumatoid arthritis. Indicators for the trial will be joint swelling and pain and levels of serological markers [177618]. A separate study is being conducted by the US National Institute for Allergy and Infectious Diseases, of thalidomide in combination with Chiron's IL-2 for the treatment of HIV infection [192218]. In vitro evidence suggests that thalidomide can inhibit the replication of HIV type 1 [169245]. In addition to the associated patent, WO-09214455, which discloses the use of thalidomide in TNF-related diseases, another Celgene patent, US-05463063, discloses a scaleable process to make high purity thalidomide [194937].
9307327 Immunopharmacological studies on collagen-induced arthritis in dark Agouti (DA) rats. 1997 Aug Dark Agouti (DA) and Lewis rat strains were tested for susceptibility to collagen-induced arthritis (CIA) and for development of cellular and humoral immune responses to type II collagen (CII). All of the DA rats developed arthritis following a single intradermal injection of more than 20 microg of CII (130-150 microg/kg rat weight) and showed a swelling rate of more than 100% in the hind paws. The swelling rate showed little deviation among the animals. There was a strong correlation between the severity of the arthritis and the strength of the immune response to CII in DA rats with CIA. Following immunization with even 800 microg of CII (3.8-4.2 mg/kg rat weight), Lewis rats showed a maximum rate of hind paw swelling of only 45%. In the pharmacological studies, prednisolone, indomethacin, FK-506 and mizoribine all suppressed arthritis in DA rats. These findings suggest that DA rats are more susceptible to CIA than Lewis rats and that CIA in DA rats as well as in Lewis rats is serviceable as an experimental animal model of rheumatoid arthritis.
11669176 Polymorphism in the MHC-encoded LMP7 gene: association with JRA without functional signifi 2001 Oct OBJECTIVE: To determine if a polymorphism in the immunoproteasome subunit LMP7 was associated with juvenile rheumatoid arthritis (JRA) and had functional significance. METHODS: The frequency of LMP7QQ+ vs QQ- (QK and KK genotypes) among 207 patients with JRA and 50 controls was determined. JRA subtypes were pauciarticular (53%), polyarticular (33%), and systemic (14%). Onset was before age 6 (early onset) in 60% of patients. The functional significance of the LMP7 polymorphism was determined by comparing incorporation of LMP7Q vs LMP7K into proteasomes. RESULTS: There was an increased frequency of LMP7QQ in patients vs controls (73 vs 56%; p = 0.016), mainly due to the pauciarticular and systemic JRA subtypes (p = 0.037), and more pronounced in early onset disease (77 vs 56%; p = 0.006). The association persisted with stratification for HLA-DR5(11) and -DPB 1 *0201 (p = 0.002 and 0.013). We found no difference in the relative incorporation of LMP7Q and LMP7K into proteasomes. CONCLUSIONS: These results support an association between LMP7QQ homozygosity and JRA, particularly early onset disease. The difference persists with stratification, at least for DR5(11) and DPB1*0201, suggesting that this effect is unlikely to be due to linkage disequilibrium with HLA alleles known to be associated with early onset pauciarticular JRA. Importantly, as there does not appear to be functional significance associated with the LMP7 polymorphism, this may be a marker for another as yet unidentified susceptibility locus.
10908407 Comparison of quantitative calcaneal ultrasound and dual energy X-ray absorptiometry in th 2000 Jul Osteoporosis is a common complication in children with chronic rheumatic diseases (CRD). Although dual energy X-ray absorptiometry (DXA) is increasingly being used to determine bone mineral density (BMD) in children, it exposes the subject to ionizing radiation and does not provide a measure of true bone density; in fact, in growing bones the increase in BMD is mainly caused by the increase in bone size. In recent years, quantitative ultrasound techniques (QUS) have been used in radiation-free assessment of bone density and "bone quality" by measurement of the ultrasound waves attenuation by bone (BUA). In the present study we made a direct comparison of BUA in the calcaneum, determined by the pediatric contact ultrasound bone analyzer (CUBA) with lumbar BMD measured by DXA, in a group of 6-18-year-old patients with CRD. The study group consisted of 53 patients affected with juvenile rheumatoid arthritis (n = 29), systemic lupus erythematosus (n = 13), and juvenile dermatomyositis (n = 11). Mean age was 13.02 +/- 2.69 years. In 22 patients (19 girls, 3 boys) both DXA and CUBA were repeated after 1 year in order to assess the mean percentage rate of BMD and BUA change over this time. Both lumbar spine BMD and calcaneal BUA measurements were lower in the CRD patients compared with a control group (P < 0.001). Calcaneal BUA was significantly correlated (r = 0.83, P < 0.001) with lumbar spine BMD. Age and sex correction (Z-score) did not change the relationship between BUA and BMD (r = 0.80, P < 0.001). A significant correlation between the mean percentage of variation (delta%) of BMD and BUA (r = 0.76, P < 0.001) was also demonstrated in the 22 patients who were evaluated prospectively. Portability, ease of use, lower cost, and absence of radiation make CUBA a promising means of evaluating BMD in children.
10902751 Subtyping of juvenile idiopathic arthritis using latent class analysis. British Paediatric 2000 Jul OBJECTIVE: To use statistical techniques to identify underlying subtypes of juvenile idiopathic arthritis (JIA) that best explain the observed relationships of clinical and laboratory variables, and to compare the statistically derived subtypes with those defined by the International League of Associations for Rheumatology (ILAR) criteria and examine them for HLA associations. METHODS: Information on 572 patients diagnosed as having JIA was summarized by 10 clinical and laboratory categorical variables (age at onset, large joint involvement, small joint involvement, polyarthritis, symmetric arthritis, spinal pain, fever, psoriasis, antinuclear antibodies [ANA], and rheumatoid factor). Latent class analysis (LCA) was used to identify underlying ("latent") classes that explained the relationships among the observed variables. Statistical models incorporating 5-8 latent classes were applied to the data. RESULTS: The 7-class model was the most appropriate. Patterns of joint involvement and the presence of ANA were influential in determining latent classes. There was some correspondence between the latent classes and the ILAR categories, but they did not coincide completely. Significant differences between the latent classes were seen for 3 HLA haplotypes (DRB1*04-DQA1*03-DQB1*03, DRB1*13-DQA1*01-DQB1*06, and DRB1*08-DQA1*0401-DQB1*0402). CONCLUSION: LCA provides a novel approach to the task of identifying homogeneous subtypes within the umbrella of JIA. In further work, the identified latent classes will be examined for associations with other candidate genes and for differences in outcome.
10092823 Adenoviral transfer of the viral IL-10 gene periarticularly to mouse paws suppresses devel 1999 Mar 15 Gene therapy is a promising new approach in the treatment of rheumatoid arthritis. Gene delivery to diseased joints offers the prospect of achieving high, local concentrations of a therapeutic gene product in a sustained manner, while minimizing exposure of nontarget organs. We report that a single administration of a modified adenovirus encoding the Epstein-Barr-derived homologue of IL-10 can suppress the development of disease for extended periods of time when injected locally within the periarticular tissue surrounding the ankle joints of mice with collagen type II-induced arthritis. Furthermore, we show that injection of an adenoviral vector carrying the IL-10 gene into a single paw can suppress development of arthritis in other, noninjected paws of the same individual. The systemic protection resulting from local gene therapy occurred in the absence of detectable levels of viral IL-10 in the serum. Circulating Ab levels to heterologous collagen were unaffected; however, treatment with viral IL-10 significantly suppressed the development of Abs to autologous mouse type II collagen. Thus, the treatment of a single joint by local delivery of the vIL-10 gene may protect multiple joints of the same individual while avoiding deleterious side effects often associated with systemic therapy.
11235018 Anti-arthritic effects of KF20444, a new immunosuppressive compound inhibiting dihydroorot 2001 Jan OBJECTIVE AND DESIGN: A newly synthesized inhibitor of pyrimidine de novo biosynthesis, KF20444 (6,7-dihydro-10-fluoro-3-(2-fluorophenyl)-5H-benzo [6,7] cyclohepta [1,2-b] quinoline-8-carboxylic acid), was evaluated as an inhibitor of dihydroorotate dehydrogenase (DHO-DHase) and tested in the rat collagen-induced arthritis (CIA) model. MATERIAL AND METHODS: Female Sprague Dawley rats, 5 weeks-old, were used for evaluation of KF20444 in the CIA model. Arthritis was evaluated by arthritis score, serum anti-type II collagen antibody titer, body weight loss, radiographical and histological changes. TREATMENT: KF20444 was orally administered 5 times per week (0.3, 1, 3 mg/kg/day). RESULTS: KF20444 inhibited rat liver dihydroorotate dehydrogenase in vitro with Ki = 8.5 +/- 3.2 nM, which was a comparable effect to that of brequinar sodium (Ki = 25.3 +/- 5.3 nM). The anti-proliferative effect of KF20444 was caused by cell cycle arrest at the S-phase. Treatment with 3 mg/kg/day of KF20444 completely prevented the development of CIA based on reduction of the arthritis score. The 50% effective dose (ED50) of KF20444 on arthritis score was 0.64 mg/kg. KF20444 ameliorated body weight loss associated with disease onset. The compound also inhibited the increase in serum anti-type II collagen antibody level, and reduced both pannus formation and bone erosion. Importantly, KF20444 suppressed the development of arthritis, even when it was administered after booster immunization of collagen. CONCLUSIONS: KF20444 is a novel immunosuppressant which inhibits DHO-DHase and its effects in CIA suggest that it could be useful in the treatment of rheumatoid arthritis.
11159186 Dynamics of early synovial cytokine expression in rodent collagen-induced arthritis : a th 2001 Feb This study was performed to elucidate pathophysiological events before and during the course of collagen-induced arthritis in Dark Agouti rats, a model for rheumatoid arthritis. Kinetic studies of local cytokine responses were determined using immunohistochemical techniques, quantified by computer-assisted image analysis. We recently reported that the macrophage-pacifying agent CNI-1493 successfully ameliorated collagen-induced arthritis. In the present trial, we investigated the potential of CNI-1493 to down-regulate pro-inflammatory cytokines. Synovial cryosections were analyzed at various time points for the presence of interleukin (IL)-1beta, tumor necrosis factor (TNF), and transforming growth factor (TGF)-beta. Unexpectedly, an early simultaneous TNF and IL-1beta expression was detected in resident cells in the lining layer, preceding disease onset and inflammatory cell infiltration by >1 week. The predominant cytokine synthesis by synovial (ED1+) macrophages coincided with clinical disease. TNF production greatly exceeded that of IL-1beta. CNI-1493 treatment did not affect the early disease-preceding TNF and IL-1beta synthesis in the lining layer. However, after disease onset, CNI-1493 intervention resulted in a pronounced reduced IL-1beta and in particular TNF expression. Furthermore, CNI-1493 significantly up-regulated synthesis of the anti-inflammatory cytokine TGF-beta and thereby shifted the balance of pro-inflammatory and anti-inflammatory cytokines in the arthritic joint in a beneficial way.
12973441 Clinical gene therapy for arthritis. 1999 Apr To overcome problems associated with conventional drug delivery in the treatment of rheumatoid arthritis (RA) our laboratory has been exploring the application of gene transfer as a means to express therapeutic proteins intraarticularly. Initial experiments in rabbit knee joints demonstrated that the gene encoding interleukin (IL)-1 receptor antagonist (IL-1RA) could be delivered to the synovial lining and expressed at a therapeutic level. The success of these experiments has led to the initiation of a clinical trial to assess the safety and efficacy of using gene therapy to treat RA. For this procedure autologous synoviocytes are retrovirally transduced in culture to express IL-1RA, and are transplanted into two metacarpophalangeal (MCP) joints of the hand. For comparative controls nonmodified synoviocytes are injected into the remaining two MCP joints. During scheduled joint replacement surgery articular tissues and fluids are recovered and analyzed for expression of the IL-1RA transgene. Nine patients will be treated in groups of three; with each group receiving successively higher numbers of transduced synoviocytes. To date five patients have completed the procedure. Thus far it has been well tolerated and intraarticular expression of the IL-1 transgene has been detected by both reverse transcriptase-polymerase chain reaction and in situ hybridization analyses. If this procedure indeed proves to be safe and feasible, future trials will address therapeutic efficacy and involve treatment in patients earlier in the progression of RA.
11329118 Therapeutic uses of gallium nitrate: past, present, and future. 1999 Nov Injectable gallium (Ga) nitrate, approved in the United States for the treatment of hypercalcemia of malignancy, has been known for more than 2 decades to have immunosuppressive properties. At therapeutic doses, it has few adverse effects, although high-dose infusions may result in severe nephrotoxicity, particularly in patients who are not adequately hydrated, and severe anemia. In animal models, Ga has been shown to have efficacy in the treatment of adjuvant arthritis, type 1 diabetes, experimental autoimmune encephalomyelitis, experimental pulmonary inflammation, cardiac allograft rejection, experimental autoimmune uveitis, endotoxic shock, and systemic lupus erythematosus. Clinical trials have demonstrated efficacy in Paget's disease of bone and activity against some malignancies, including epithelial ovarian carcinoma, non-squamous cell carcinoma of the cervix, bladder cancer, and non-Hodgkin's lymphoma. Other clinical trials underway include studies of sarcoidosis and rheumatoid arthritis. Future studies should be conducted not only in other autoimmune diseases, such as multiple sclerosis, but also in graft-versus-host disease, leprosy, and acquired immunodeficiency syndrome (AIDS).
10731301 Balneotherapy at the Dead Sea area for knee osteoarthritis. 1999 Oct BACKGROUND: Balneotherapy at the Dead Sea area has been applied in various inflammatory rheumatic diseases such as rheumatoid arthritis and psoriatic arthritis. The efficacy of balneotherapy at the Dead Sea area for the treatment of degenerative rheumatic diseases has not yet been formally evaluated. OBJECTIVE: To evaluate the efficacy of balneotherapy at the Dead Sea area in patients suffering from osteoarthritis of the knees. METHODS: Forty patients were randomly allocated into four groups of 10 patients. Group I was treated by bathing in a sulphur pool, group 2 by bathing in the Dead Sea, group 3 by a combination of sulphur pool and bathing in the Dead Sea, and group 4 served as the control group receiving no balneotherapy. The duration of balneotherapy was 2 weeks. RESULTS: Significant improvement as measured by the Lequesne index of severity of osteoarthritis was observed in all three treatment groups, but not in the control group. This improvement lasted up to 3 months of follow-up in patients in all three treatment groups. CONCLUSION: Balneotherapy at the Dead Sea area has a beneficial effect on patients with osteoarthritis of the knees, an effect that lastas at least 3 months.
9550479 Characteristic magnetic resonance imaging entheseal changes of knee synovitis in spondylar 1998 Apr OBJECTIVE: To use magnetic resonance imaging (MRI) in patients with rheumatoid arthritis (RA) and spondylarthropathy (SpA) to determine if the primary site of abnormality differs. METHODS: Twenty patients with recent-onset knee effusion (10 with SpA and 10 with RA) were evaluated using fat-suppressed MRI. Knee joint effusion and synovitis were confirmed using ultrasonography. MRI scans were independently scored by 2 observers who were blinded to the patient's diagnosis. RESULTS: All 10 of the SpA patients, but only 4 of the 10 RA patients, had focal peri-entheseal high signal (compatible with fluid or edema) outside the joint (P = 0.01). Six of the SpA patients had bone marrow edema that was maximal at entheseal insertions; in 4 cases this was multifocal. No RA patients showed such an abnormality (P = 0.01). CONCLUSION: Prominent entheseal abnormalities on MRI are a consistent feature of new-onset synovitis in SpA, but are a minor feature of RA. This finding has important implications for the diagnosis, classification, and mechanisms of synovitis in patients with SpA.