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ID PMID Title PublicationDate abstract
14677188 Serum cytokine profiles in patients with adult onset Still's disease. 2003 Nov OBJECTIVE: Adult onset Still's disease (AOSD) is a systemic inflammatory disorder characterized by fever, arthritis, and rash. Although the pathogenesis is not known, immunologically mediated inflammation occurs in active AOSD. To evaluate the pathogenesis and disease activity of AOSD, we measured serial serum concentrations of several cytokines in patients with active and inactive disease. METHODS: Seventeen patients diagnosed as having AOSD were enrolled. We analyzed clinical and laboratory findings retrospectively. Serial serum samples were obtained from 14 patients with active and inactive AOSD. Interleukin 18 (IL-18), soluble IL-2 receptor (sIL-2R), IL-6, interferon-g (IFN-g), and IL-8 were determined by ELISA. RESULTS: Serum levels of IL-18, IFN-g, and IL-8 were significantly higher in patients with AOSD than in healthy controls (p < 0.01), but there were no significant differences between patients with active and inactive AOSD. Serum sIL-2R levels tended to be higher in the active state than in healthy controls, but there was no statistically significant difference between the 2 groups. Serum sIL-2R levels decreased significantly with antiinflammatory therapy (p < 0.05). Serum IL-18 and sIL-2R levels correlated significantly with serum ferritin levels in the active AOSD group (p < 0.05). CONCLUSION: Overproduction of IL-18 may contribute to the pathogenic mechanism of AOSD, and serum sIL-2R levels may be used as a marker for monitoring disease activity in AOSD.
14598044 Clinical and serological associations of autoantibodies to GW bodies and a novel cytoplasm 2003 Dec A novel autoantigen named GW182 was recently identified when the serum from a patient with a sensory ataxic polyneuropathy was used to immunoscreen a HeLa cDNA library. Unique features of the GW182 protein include 39 repeats of glycine (G) and tryptophan (W) residues, binding to a subset of messenger RNA and localization to unique structures within the cytoplasm that were designated GW bodies (GWBs). The goal of the present study was to identify the clinical features of patients with anti-GW182 antibodies and to characterize the B cell anti-GW182 response by defining the epitopes bound by human autoantibodies. The most common clinical diagnosis of patients with anti-GW182 antibodies was Sjögren's syndrome followed by mixed motor/sensory neuropathy, and systemic lupus erythematosus. Of interest, 5 (28%), 9 (50%), and 3 (17%) of the 18 sera that react with GWBs had autoantibodies to the GW182 and the 52 kDa and 60 kDa SS-A/Ro autoantigens, respectively. Epitopes bound by the human autoantibodies were mapped to the GW-rich middle part of the protein, the non-GW rich region, and the C-terminus of GW182 protein. None of the GW182 epitopes had significant sequence similarities to other known proteins. GW182 represents a new category of ribonucleoprotein autoantigens.
12610426 [Anti-SSA/Ro and anti-SSB/La antibodies. What's new?]. 2002 Dec Anti-SSA/Ro and anti-SSB/La autoantibodies recognize different epitopes on polypeptides associated with small RNAs called scYRNA situated mostly in the cytoplasmic compartment (70%) and few in the nuclear compartment (30%). These hYRNPs (h=human) can be found on the cytoplasmic membrane or in small blebs during apoptosis after various stimuli such as UVB, 17-beta-estradiol, viral infection, TNF alpha and other cellular apoptosis inducing molecules. At least two major different proteins are called SSA/Ro: a 52 kDa Ro (with two subtypes alpha and beta) and a 60 kDa Ro. There is only one SSB/La protein of 48 kDa. In some circumstances, other proteins such as calreticuline (MW 57 kDa) join Ro/SSA proteins on some YRNAs. Anti-SSA/Ro antibodies are detected in the sera of 30% of patients with SLE, even during preclinical setting; anti-Ro/SSA are strongly associated (90%) with some subtypes of SLE such as old-onset (>50 y) SLE, subacute lupus erythematosus, drug-induced subacute lupus erythematosus and in patients with hereditary C2 or C4 or C1q deficiency with lupus or lupus-like disease. Anti-SSA/Ro are also associated with primary Sjögren syndrome (50% to 60%) and with undifferenciated connective tissue disease (UCTD). Anti-SSA/Ro antibodies are almost always present in sera of mothers with babies with neonatal lupus syndrome (NNL) and with complete congenital heart block (CCHB). This last event is very unusual in pregnant patients with anti-Ro/SSA antibodies (1% to 2% of primigeste women). Some good evidences such as experimental models in vitro or ex-vivo, argue for the responsibility of maternal anti-Ro/SSA 52 kDa and/or anti-La/SSB antibodies (or associated IgG antibodies) as major etiologic factor of CCHB and NNL. IgG anti-Ro 52 beta kDa has been shown able to interrupt the atrioventricular conduction as well as the L calcium channel influx of fetal cardiocytes. Other factors must be taken into account to explain discordant twins (with and without CCHB). More recently anti-Ro/SSA antibodies were associated with QT interval prolongation in newborns without CCHB.
11940237 A novel lacrimal gland autoantigen in the NOD mouse model of Sjögren's syndrome. 2002 Mar Recent research has demonstrated a crucial role for autoantibodies in the pathogenesis of Sjögren's syndrome (SS)-like disease in the non-obese diabetic (NOD) mouse, but it remains to be determined which antibody species among all those present are directly related to the various aspects of pathology. To identify autoantigens in the NOD mouse system, we have taken the approach of using immunoglobulin (Ig)G purified from sera of NOD mice exhibiting SS-like symptoms to screen cDNA expression libraries derived from exocrine gland mRNA. Here we report the identification of a novel autoantigen, designated LGP10, expressed in lacrimal and submandibular glands. Autoantibodies to this protein are prominent in the sera of NOD mice starting at 11-12 weeks of age, but not in control nonautoimmune mice. LGP10 has no known function, but bears similarities to various other proteins produced by epithelia. Interestingly, all of these similar proteins have been linked to immunosuppression and/or steroid binding, both processes that could have a significant impact on pathological features of SS.
12233881 Interleukin 10 (IL-10) influences autoimmune response in primary Sjögren's syndrome and i 2002 Sep OBJECTIVE: To investigate the association between serum levels of interleukin 10 (IL-10), the synthesis of autoantibodies, salivary gland disease activity, clinical manifestations, and IL-10 microsatellite polymorphism in patients with primary Sjögren's syndrome (pSS). METHODS: Serum IL-10 and autoantibody levels [IgG anti-Ro and anti-La, total and IgA rheumatoid factor (RF)] were measured by ELISA. A minor salivary gland (MSG) biopsy was performed in all patients and the focus score was determined as a measure of salivary gland disease activity. In addition, IL-10 microsatellite typing was performed by polymerase chain reaction technique. RESULTS: IL-10 concentration was higher in patients (n = 39) than in controls (n = 15) (21.4 +/- 6.7 vs 2.5 +/- 3.5 pg/ml; p = 0.001). We found a significant positive correlation between IL-10 levels and titers of IgA RF, anti-Ro, and anti-La antibodies, as well as focus score. In comparison with patients with low IL-10 production (< 9.5 pg/ml), patients producing high IL-10 had significantly more episodes of cutaneous vasculitis and a higher proportion of them carried the IL-10.G9 allele. CONCLUSION: Autoimmune response in pSS patients as well as salivary gland disease activity and cutaneous involvement appears to be mediated by IL-10 levels; in turn, there is a linkage with IL-10 gene polymorphism.
15328883 Dermatomyositis associated with Sjögren's syndrome: VEGF involvement in vasculitis. 2004 Jul Two patients with dermatomyositis complicated with Sjögren's syndrome (SjS), are reported. Both patients exhibited sensory-dominant polyneuropathy, compatible with neurologic involvement in SjS. Vascular endothelial growth factor (VEGF) levels were increased in their plasma. Histological examination demonstrated vasculitic changes in biopsied specimens of muscle and salivary glands from the patients, and VEGF was overexpressed in the vasculitic lesions. These findings suggest that VEGF overexpression was associated with the development of vasculopathy in skeletal muscle and salivary glands and possibly in the peripheral nervous system.
15223808 Inflammatory mediators in autoimmune lacrimal gland disease in MRL/Mpj mice. 2004 Jul PURPOSE: MRL/MpJ-fas(+)/fas(+) (MRL/+) and MRL/MpJ-fas(lpr)/fas(lpr) (MRL/lpr) mice are congenic substrains of mice that have spontaneously developing lacrimal and salivary gland inflammation and are models for the human disorder Sjögren's syndrome. Nitric oxide (NO) and tumor necrosis factor (TNF)-alpha are proinflammatory and potential mediators of tissue damage. The presence of the inducible form of nitric oxide synthase (iNOS), which catalyzes the production of NO, and the presence TNF-alpha in the lacrimal glands of MRL/MpJ mice were assessed. METHODS: Lacrimal glands from MRL/+ and MRL/lpr mice, at ages 1 through 9 months, were evaluated by real-time RT-PCR for iNOS and TNF-alpha mRNA and by immunohistochemistry for the presence of iNOS and of TNF-alpha. Age-matched BALB/c lacrimal glands were used as the control. RESULTS: By quantitative real-time PCR (qPCR), mRNA for iNOS was detected in the lacrimal glands in significantly greater amounts in both MRL/+ (median, normalized to 18S rRNA, 2.90; P < 0.0003) and MRL/lpr mice (median 6.84, P < 0.001) than in BALB/c mice (median 0.34). By qPCR, mRNA for TNF-alpha in the lacrimal glands was detected in significantly greater amounts in aged MRL/+ mice than in BALB/c mice (median, normalized to actin, 221.8 vs. 77.8, P = 0.011) and in MRL/lpr mice than in BALB/c mice (median 136.7 vs. 72.5, P = 0.001). Immunohistochemistry demonstrated both iNOS and TNF-alpha in scattered mononuclear cells throughout the lacrimal glands and in mononuclear cells at the junction of the focal inflammatory infiltrates and normal acinar tissue in both MRL/+ and MRL/lpr mice. CONCLUSIONS: As demonstrated by the greater presence of iNOS and TNF-alpha in the lacrimal glands of MRL/MpJ mice than in control glands, both NO and TNF-alpha are potential mediators of lacrimal gland damage in these murine models of Sjögren's syndrome.
15153869 A comparison of the hormone levels in patients with Sjogren's syndrome and healthy control 2004 May OBJECTIVE: The purpose of this study was to compare the level and relative ratio of estrogen, progesterone, and prolactin in patients with Sjögren's syndrome and healthy controls. STUDY DESIGN: Serum samples were collected from 17 SS patients and 19 age-, sex- and race-matched controls. All subjects were postmenopausal females who were not currently on hormone replacement therapy. Prolactin levels were measured using ELISA and progesterone and estrogen were measured using EIA. RESULTS: Mann-Whitney U test revealed a significantly higher levels of prolactin among patients than controls (11.41 ng/ml vs. 6.74 ng/ml, p=0.003) with significantly higher prolactin/ progesterone (18.88 vs. 8.14, p=0.02) and estrogen/ progesterone (71.51 vs. 42.02, p=0.05) ratios. No significant differences were observed in the levels of estrogen and progesterone between patients and controls. CONCLUSION: Abnormal levels and relative ratios of hormones may play a role in the pathogenesis of Sjögren's syndrome.
15077310 Mortality and causes of death in primary Sjögren's syndrome: a prospective cohort study. 2004 Apr OBJECTIVE: This study was undertaken to analyze standardized mortality ratios (SMRs) and causes and predictors of death in primary Sjögren's syndrome (SS) diagnosed according to 3 different classification criteria sets (the Copenhagen criteria, the European criteria, and the American-European consensus criteria (AECC). METHODS: A linked registry study using information from the Malmö Primary SS Registry combined with the Swedish Cause-of-Death Registry was performed, and SMRs were calculated. Kaplan-Meier survival curves and log rank tests were used to compare survival probability between subgroups of patients with primary SS. Cox regression analysis was used to study the predictive value of various laboratory findings at the time of diagnosis. RESULTS: Four hundred eighty-four patients with a median followup of 7 years (range 1 month to 17 years 11 months) were included. The SMR for those fulfilling the AECC (n = 265) was 1.17 (95% confidence interval [95% CI] 0.81-1.63). Thirty-four deaths occurred in this group of patients. Excess mortality was found only for lymphoproliferative malignancy (cause-specific SMR 7.89 [95% CI 2.89-17.18]), corresponding to 2.53 excess deaths per 1,000 person-years at risk. In those not fulfilling the AECC (n = 219), 14 deaths occurred, the SMR was 0.71 (95% CI 0.39-1.20), and no excess mortality due to any specific cause was found. Hypocomplementemia, defined as C3 and/or C4 values in the lowest quartile of the SS patients' values at the time of diagnosis, was a significant predictor of death, mainly due to lymphoproliferative malignancy. CONCLUSION: No increased all-cause mortality could be detected for patients with primary SS compared with the general population. When subgroups of primary SS were compared, excess mortality due to lymphoproliferative malignancy was found in patients fulfilling the AECC, the strongest predictor for unfavorable outcome being low C3 and/or C4 levels at the time of diagnosis.
14973428 FasL and Bax genes are differentially expressed in acinar epithelium and inflammatory cell 2003 Oct AIM: Assess the expression of FasL, Bax, TNFa and IL-6, genes in salivary glands of primary Sjögren patients. METHODS: Twenty minor salivary glands from patients with primary Sjögren syndrome were studied by in situ hybridization with cDNA fluorescent probes. An equal number of control biopsies were included. RESULTS: Sjögren salivary glands differentially display the inflammatory cytokines and pro-apoptotic mRNAs as follows: mononuclear infiltrating cells exhibited IL-6 and TNFa, whereas the ductal epithelium and acinary cells mainly expressed FasL and Bax. Control biopsies were negative. CONCLUSION: Present data suggest that local production of inflammatory cytokines would induce the Fas and Bax pathways committing the ductal epithelium and the acinary cells to apoptosis.
14872501 Association of transforming growth factor beta1 and tumor necrosis factor alpha polymorphi 2004 Feb OBJECTIVE: To determine whether cytokine gene polymorphisms of interferon-gamma (IFNgamma), interleukin-6 (IL-6), IL-10, tumor necrosis factor alpha (TNFalpha), and transforming growth factor beta1 (TGFbeta1) predispose subjects to the development of primary Sjögren's syndrome (SS). METHODS: Single-base-exchange cytokine gene polymorphisms were analyzed in 129 French patients with primary SS who fulfilled the American-European Consensus Group criteria, as well as in 96 unrelated healthy subjects. RESULTS: The frequency of the TNF-308A (TNF2) allele was significantly higher in the SS patients (26% versus 11%). This TNF2 association was restricted to patients with anti-SSB (37% versus 11% in controls). Stratification did not reveal an independent effect of TNF2 and HLA-DRB1*03 on disease or on anti-SSB antibody secretion. The frequency of allele C at codon 10 of TGFbeta1 was strongly increased in the subgroup of patients with anti-SSB; this allele acted synergistically with DRB1*03 to predispose patients to the secretion of anti-SSB. The IL-10 GCC haplotype carrier rate was significantly higher in SS patients than in controls (67% versus 48%), but the IL-10 allele and genotype frequencies were not significantly different. No association was found between IL-6 or IFNgamma polymorphisms and primary SS. CONCLUSION: TNF2 was associated with anti-SSB antibody secretion, although this association was not independent of the association with DRB1*03. Allele C at codon 10 of TGFbeta1 was found to act synergistically with DRB1*03 in predisposing patients to the secretion of anti-SSB. These results therefore suggest that most of the known genetic predisposition to primary SS might concern the pattern of autoantibody diversification.
12115247 Two NOD Idd-associated intervals contribute synergistically to the development of autoimmu 2002 May OBJECTIVE: The NOD mouse is genetically predisposed to the development of at least 2 autoimmune diseases, autoimmune diabetes and autoimmune exocrinopathy (AEC). More than 19 chromosomal intervals (referred to as Idd regions) that contribute to diabetes susceptibility in the NOD mouse model have been identified, but only 2 chromosomal intervals (associated with Idd3 and Idd5) have been shown to control sialadenitis. In the present study, we bred the Idd3 and Idd5 chromosomal intervals from NOD mice into non-autoimmune C57BL/6 mice to determine if these intervals recreate a Sjögren's syndrome (SS)-like phenotype. METHODS: C57BL/6.NODc3 mice carrying Idd3 and C57BL/6.NODc1t mice carrying Idd5 were crossed and intercrossed to generate a C57BL/6.NODc3.NODc1t mouse line homozygous for the Idd3 and Idd5 chromosomal intervals on an otherwise disease-resistant genetic background. C57BL/6.NODc3.NODc1t mice were evaluated for biochemical, pathophysiologic, and immunologic markers characteristic of the SS-like phenotype present in the NOD mouse. RESULTS: C57BL/6.NODc3.NODc1t mice fully manifested the SS-like phenotype of the NOD mouse, including decreased salivary and lacrimal gland secretory flow rates, increased salivary protein content due in part to less fluid, aberrant proteolytic enzyme activity, decline in amylase activity, appearance of autoantibodies to exocrine gland proteins, and glandular lymphocytic focal infiltrates. Loss of secretory function occurred more rapidly in C57BL/6.NODc3.NODc1t mice (by 12 weeks of age) than in NOD mice (by 16 weeks of age). No signs of insulitis or autoimmune (type 1) diabetes were observed in the C57BL/6.NODc3.NODc1t mice. CONCLUSION: Genes located within the 2 chromosomal intervals Idd3 and Idd5 appear necessary and sufficient for manifestation of AEC. We propose that this murine model of SS-like disease be designated C57BL/6.NOD-Aec1Aec2. Identification of specific genes within the Aec1 and Aec2 genetic regions should help elucidate the mechanism(s) underlying SS-like disease.
15142275 Effect of phospholipase A2 inhibitory peptide on inflammatory arthritis in a TNF transgeni 2004 We evaluated the therapeutic effect of secretory phospholipase A2 (sPLA2)-inhibitory peptide at a cellular level on joint erosion, cartilage destruction, and synovitis in the human tumor necrosis factor (TNF) transgenic mouse model of arthritis. Tg197 mice (N = 18) or wild-type (N = 10) mice at 4 weeks of age were given intraperitoneal doses (7.5 mg/kg) of a selective sPLA2 inhibitory peptide, P-NT.II, or a scrambled P-NT.II (negative control), three times a week for 4 weeks. Untreated Tg197 mice (N = 10) were included as controls. Pathogenesis was monitored weekly for 4 weeks by use of an arthritis score and histologic examinations. Histopathologic analysis revealed a significant reduction after P-NT.II treatment in synovitis, bone erosion, and cartilage destruction in particular. Conspicuous ultrastructural alterations seen in articular chondrocytes (vacuolated cytoplasm and loss of nuclei) and synoviocytes (disintegrating nuclei and vacuoles, synovial adhesions) of untreated or scrambled-P-NT.II-treated Tg197 mice were absent in the P-NT.II-treated Tg197 group. Histologic scoring and ultrastructural evidence suggest that the chondrocyte appears to be the target cell mainly protected by the peptide during arthritis progression in the TNF transgenic mouse model. This is the first time ultrastructural evaluation of this model has been presented. High levels of circulating sPLA2 detected in untreated Tg197 mice at age 8 weeks of age were reduced to basal levels by the peptide treatment. Attenuation of lipopolysaccharide- and TNF-induced release of prostaglandin E2 from cultured macrophage cells by P-NT.II suggests that the peptide may influence the prostaglandin-mediated inflammatory response in rheumatoid arthritis by limiting the bioavailability of arachidonic acid through sPLA2 inhibition.
15520107 Health care preferences and priorities of adolescents with chronic illnesses. 2004 Nov BACKGROUND: Efforts to make health care for adolescents with chronic illnesses more patient-centered must be grounded in an understanding and clear measures of adolescents' preferences and priorities. OBJECTIVE: To develop a measure of health care preferences of adolescents with chronic illnesses and to determine demographic, developmental, and health factors associated with adolescents' preferences. DESIGN: Mixed-method questionnaire development and survey. SETTING: Subspecialty clinics of a tertiary care children's hospital. PARTICIPANTS: All adolescents (age: 11-19 years) with juvenile rheumatoid arthritis, sickle cell disease, inflammatory bowel disease, or cystic fibrosis of at least 2-year duration who were being treated at the participating center were eligible to participate, and 155 of 251 did so (62%). The participants had a mean age of 15.5 +/- 2.4 years, 45% were male, and 75% were white. INTERVENTION: None. MAIN OUTCOME MEASURES: Ratings of 65 items related to quality of care and 17 items related to physician-patient communication styles. RESULTS: An 82-item questionnaire, devised from qualitative analysis of focus group results, contained 65 Likert scale items that adolescents considered important for health care quality and 17 forced-choice items related to adolescents' preferences for communication. Among the first 65 items, the group of questions related to physician trust and respect had the highest rating of 5.24 +/- 0.62 of 6, followed by patient power and control (mean rating: 4.72 +/- 0.77) and then caring and closeness in the patient-doctor relationship (mean rating: 4.19 +/- 0.91). For the communication items, the adolescents, on average, preferred communication directly to them rather than to their parents and were nearly neutral regarding physicians' inquiries about personal issues. CONCLUSIONS: Participants rated aspects of interpersonal care (especially honesty, attention to pain, and items related to respect) as most important in their judgments of quality. As in most previous studies of adults, technical aspects of care were also rated highly, suggesting that adolescents understand and value both scientific and interpersonal aspects of care.
14674010 Chemokine receptor expression and in vivo signaling pathways in the joints of rats with ad 2003 Dec OBJECTIVE: This study was undertaken to characterize the role of CC chemokines and their receptors in rat adjuvant-induced arthritis (AIA), a model for rheumatoid arthritis (RA). Furthermore, we investigated the signaling pathways associated with CC receptors as well as the cell type distribution of the receptors. METHODS: Using TaqMan real-time reverse transcription-polymerase chain reaction, Western blot analysis, and immunohistochemistry, we defined chemokine and chemokine receptor messenger RNA (mRNA) expression, CC chemokine receptor (CCR) protein activation during the disease course, CCR-associated signaling pathways, and immunopositive CCR5, phosphorylated signal transducer and activator of transcription 1 (p-STAT-1), and p-STAT-3 cells in rat AIA versus control joints. RESULTS: We showed significant up-regulation of CCR1, CCR2, CCR5, and macrophage inflammatory protein 1beta/CCL4 mRNA in AIA on post-adjuvant injection day 18, coincident with peak inflammation. Additionally, increases in tyrosine phosphorylation of CCR1 (days 14, 18, 21, and 24), CCR2 (days 14 and 18), and CCR5 (days 14, 18, and 21) were detected in AIA rats compared with control (nonarthritic) rats. JAK-1, STAT-1, and STAT-3 were associated with CCR1 and were highly tyrosine phosphorylated on days 14 and 18. Moreover, CCR2 was associated with JAK-2, STAT-1, and STAT-3 on day 18. The association of STAT-1 and STAT-3 with CCR5 on days 18 and 21 correlated with JAK-1 phosphorylation and binding on day 18. However, the activation of JNK was not associated with CCR5 activation in rat AIA. Immunohistochemical analysis demonstrated that the expression of CCR5, p-STAT-1, and p-STAT-3 was detected on synovial lining cells, macrophages, and endothelial cells in arthritic rat ankles on post-adjuvant injection day 18. While the majority of the CCR5 and p-STAT-1 immunostaining was on synovial lining cells and macrophages, p-STAT-3 was predominantly expressed on endothelial cells. CONCLUSION: CCR1, CCR2, and CCR5 mRNA expression and tyrosine phosphorylation increased with peak inflammation in the AIA model. CCR1, CCR2, and CCR5 tyrosine phosphorylation are associated with the JAK/STAT-1/STAT-3 pathway at different stages of rat AIA, as well as with macrophage and endothelial cell infiltration. However, their signaling activation overlaps with peak inflammation. Up-regulation and activation of CCRs may play a role in macrophage and endothelial cell infiltration in rat AIA joints in addition to activating the associated signaling pathways. The downstream intermediate signaling proteins associated with CC receptors may be used as potential tools to control inflammation in RA.
15488689 Clinical trials in rheumatic diseases: designs and limitations. 2004 Nov Randomized controlled clinical trials provide the best method to distinguish a drug from placebo without the inevitable selection biases that are seen in standard clinical care. This article reviews designs and limitations of clinical trials that are used in rheumatic diseases. The primary design in clinical trials is a parallel, in which patients are randomized in parallel to different therapies at different dosages or placebo. In recent years, other designs have been used increasingly, including "step-up," "step-down," and "cross-over" designs. Limitations of clinical trials in chronic diseases include a short time frame versus the long duration of disease, inclusion and exclusion criteria, use of surrogate markers that may not represent clinically relevant markers, statistical significance does not necessarily indicate clinical significance necessarily, and the fact that a control group does not assure the absence of bias. Therefore, long-term databases are needed to supplement clinical trials in analyzing results of therapy for rheumatoid arthritis.
15357791 Shoulder hemiarthroplasty to manage haemophilic arthropathy: two case studies. 2004 Sep Bleeds within the shoulder joint can lead to significant joint destruction and may have associated pain, decreased range of movement (ROM), and impaired function. Conservative management should involve prompt administration of Factor VIII and physiotherapy to address all surrounding structures so as to minimize further damage. If conservative management fails to relieve severe, unremitting shoulder pain in the presence of underlying arthropathy, then arthroplasty may be considered. Outcomes of arthroplasties performed for osteoarthritis and rheumatoid arthritis appear favourable. Few articles, however, have addressed shoulder arthroplasty to manage haemophilic arthropathy, and no reports have documented the rehabilitation process. Three hemiarthroplasties were performed at the Royal Brisbane and Women's Hospital on two men with haemophilia. There were no surgical or postoperative complications. Rehabilitation included intensive physiotherapy. The results in each case revealed a decrease in pain, and an increase in ROM and function postoperatively. These findings suggest that hemiarthroplasty with postoperative physiotherapy may be a feasible option to manage severe, chronic and progressing shoulder pain as a result of haemophilic arthropathy of the shoulder.
15304013 Identification of two new HLA-DRB1 alleles: HLA-DRB1*1350 and DRB1*140502. 2004 Sep Two new HLA-DRB1 alleles have been found by using high-resolution sequence-based typing. The two sequences have been officially named DRB1*1350 (HWS10001327-AY048687) and DRB1*140502 (HWS10001790-AY129430). DRB1*1350 differs from DRB1*110101 by two amino acids at positions 37 (Y-->N) and 58 (A-->E). This allele may arise from gene conversion between DRB1*110101 and DRB1*130201 or DRB1*030101, which are commonly found in Taiwan populations. The other allele, DRB1*140502, obtained from a patient with rheumatoid arthritis, differs from DRB1*140501 at codon 58 (GCC-->GCT). However, it causes no change in amino acid sequence and would therefore not have direct clinical implications.
15264435 Technology evaluation: abatacept, Bristol-Myers Squibb. 2004 Jun Bristol-Myers Squibb is developing the fusion protein abatacept for the potential treatment of various immunological disorders, including rheumatoid arthritis, multiple sclerosis and systemic lupus erythematosus. Abatacept is undergoing phase III clinical trials.
15131992 [Methods of monitoring oxidation-reduction balance and its potential role in diagnostics]. 2004 Apr 4 Results of the latest investigations confirm that the injury of redox homeostasis of human organism can be the starting point of many diseases. The pathogenesis of these diseases, including atherosclerosis, diabetes mellitus, chronic liver diseases, renal failure, rheumatoid arthritis and neurodegenerative diseases could be cleared up more deeply by the investigation of parameters of oxidative stress and by the observation of their changes in connection with the different organ and tissue damages. It is well known, that individuals with lowered antioxidant defences may be at greater risk of developing diseases induced by free radicals. The goal of the authors is to direct attention to the possible role of some redox parameters in detecting of general health status of the human body and in the risk assessment of the different diseases. These measurements can perhaps help the clinician in determining optimal treatment and monitoring its effectiveness.