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

ID PMID Title PublicationDate abstract
11751969 HLA-DR1 (DRB1*0101) and DR4 (DRB1*0401) use the same anchor residues for binding an immuno 2002 Jan 1 Rheumatoid arthritis is an autoimmune disease in which susceptibility is strongly associated with the expression of specific HLA-DR haplotypes, including DR1 (DRB1*0101) and DR4 (DRB1*0401). As transgenes, both of these class II molecules mediate susceptibility to an autoimmune arthritis induced by immunization with human type II collagen (hCII). The dominant T cell response of both the DR1 and DR4 transgenic mice to hCII is focused on the same determinant core, CII(263-270). Peptide binding studies revealed that the affinity of DR1 and DR4 for CII(263-270) was at least 10 times less than that of the model Ag HA(307-319), and that the affinity of DR4 for the CII peptide is 3-fold less than that of DR1. As predicted based on the crystal structures, the majority of the CII-peptide binding affinity for DR1 and DR4 is controlled by the Phe(263); however, unexpectedly the adjacent Lys(264) also contributed significantly to the binding affinity of the peptide. Only these two CII amino acids were found to provide binding anchors. Amino acid substitutions at the remaining positions had either no effect or significantly increased the affinity of the hCII peptide. Affinity-enhancing substitutions frequently involved replacement of a negative charge, or Gly or Pro, hallmark amino acids of CII structure. These data indicate that DR1 and DR4 bind this CII peptide in a nearly identical manner and that the primary structure of CII may dictate a different binding motif for DR1 and DR4 than has been described for other peptides that bind to these alleles.
15188323 Multifaceted intervention to improve rheumatologists' management of glucocorticoid-induced 2004 Jun 15 OBJECTIVE: To assess the effectiveness of a multifaceted intervention to improve the management of glucocorticoid-induced osteoporosis (GIOP). METHODS: Of 21 rheumatologists, 11 were randomly assigned to a 3-part intervention consisting of a lecture and discussion regarding optimal management of GIOP, a confidential doctor-specific audit regarding management of GIOP, and a reminder mailing including concise pharmacologic recommendations. The remaining 10 rheumatologists received no special education. Patients with rheumatoid arthritis (RA) taking oral glucocorticoids seen in the 2 months after the intervention were followed for 6 months. Medical records were assessed to determine the proportion undergoing bone mineral density testing or receiving pharmacologic interventions for GIOP during the 6 months before and 6 months after the intervention. RESULTS: There were 373 patients with RA taking oral glucocorticoids whose records were assessed. Patients in both arms of the trial were similar with respect to age, sex, menopausal status, glucocorticoid dosage and duration, duration of RA, disease-modifying antirheumatic drug use, and the proportion with comorbid conditions. At baseline, there was no significant difference between the patients with respect to osteoporosis medication use (intervention 32% versus control 34%) or bone densitometry use (intervention 9% versus control 5%). After the intervention and a 6-month followup period, there were no differences in treatment (intervention 33% versus control 38%) or bone densitometry use (intervention 8% versus control 8%). Adjusting for patient and physician characteristics did not significantly change these results. CONCLUSION: A multifaceted intervention for GIOP, including doctor education, practice audit, and treatment suggestions, had no significant benefit on testing or treatment by rheumatologists over a 6-month followup period. Other intervention approaches need to be tested.
15599524 Clinical efficacy of radiation synovectomy in digital joint osteoarthritis. 2005 May PURPOSE: Radiation synovectomy was developed for local treatment of rheumatoid arthritis. In this study, the long-term efficacy of radiation synovectomy was retrospectively evaluated in patients with osteoarthritis (activated arthrosis) of the digital joints using an algofunctional score. METHODS: Fifty-three digital joints in 29 patients (mean age 64.8 years) were treated by intra-articular injection of 169Er citrate. All joints were painful despite pharmacotherapy and showed an elevated blood pool pattern in a pretherapeutic three-phase bone scan, indicative for local synovitis. The patients were asked to classify their complaints with respect to different daily manual activities on a ten-step pain scale from 1 (total disability) to 10 (lack of any impairment) prior to and after treatment, with a mean follow-up of 41 months. Local signs of osteoarthritis such as joint swelling or pain were additionally evaluated and were scored from progression of complaints to excellent improvement based on patient self-evaluation. RESULTS: All patients reported a pronounced improvement in their manual activities. The mean total score of 4.73+/-0.58 for all activities prior to treatment increased significantly to 6.79+/-0.47 after radiation synovectomy (p<0.05). The best results were obtained in the thumb base joints, whereas distal interphalangeal joints were frequently resistant to therapy. CONCLUSION: Radiation synovectomy is highly effective in digital joint osteoarthritis with concomitant local synovitis.
15533683 Simple and rapid determination of adenosine in human synovial fluid with high performance 2004 Nov 19 A simple, fast, sensitive and selective reversed-phase high performance liquid chromatography-mass spectrometry coupling with an electrospray ionization (ESI) interface method is described for the determination of adenosine in human synovial fluid. This method involved the use of the [M + H](+)ions of adenosine and 2-chloroadenosine (internal standard for the assay) at m/z 268 and 302 in positive ion mode with selective ion monitoring (SIM). Separation was carried out on a 2.0 x 150 mm Shimadzu VP-ODS column by using an isocratic elution with a mobile phase consisting of water (94%),methanol (5%) and formic acid (1%). No interference with the components of the biological matrix was observed in the determination conditions. The calibration curve was linear in the range of 0.2-140 microgml(-1). The limits of quantification (LOQ) and detection (LOD) were 0.2 and 0.03 microgml(-1), respectively. The standard recoveries were between 93.3 and 104.0%. The method was successfully applied to determination of adenosine in some synovial fluids of patients affected by rheumatoid arthritis.
15507288 Antiprothrombin antibodies--are they worth assaying? 2004 According to the preliminary classification criteria of the antiphospholipid syndrome (APS) (Sapporo Criteria), beta2-glycoprotein I (beta2GPI)-dependent anticardiolipin antibodies (aCL) and lupus anticoagulant (LA) are the only laboratory tests considered as criteria for the classification of the APS. Recently, antibodies against phosphatidylserine-prothrombin complex (aPS/PT) have been detected and these antibodies, rather than antibodies against prothrombin alone, are closely associated with APS and LA. We assessed the sensitivity and specificity of aPS/PT for the diagnosis of APS in our population of patients with a variety of autoimmune disorders and investigated whether aPS/PT could be used as diagnostic test in patients suspected of having APS. The study population comprised 219 patients with autoimmune diseases including 82 patients with APS and 137 without APS (55 systemic lupus erythematosus, 32 rheumatoid arthritis, 10 primary Sjogren's syndrome, 8 scleroderma, 5 Behcet's disease and 27 other rheumatic diseases). IgG/M aPS/PT were measured by ELISA using phosphatidylserine-prothrombin complex as antigen immobilized on ELISA plates in the presence of CaCl2. IgG/M aCL were measured by standard methods and LA was detected by clotting assays. aPS/PT, aCL and LA were more frequently found in patients with APS (47, 46 and 69, respectively) than in those without APS (11, 19 and 29, respectively) (OR 95% [CI]; 15.4 [7.2-32.7], 7.9 [4.1-15.2, 19.8 [9.6-40.6], respectively]. The sensitivity of each assay for the diagnosis of APS was 57%, 56% and 86% with a specificity of 92%, 86% and 79%, respectively. aPS/PT and aCL have similar diagnostic value for APS, therefore, we propose that aPS/PT should be further explored, not only for research purposes, but also as a candidate of one of the laboratory criteria for the classification of the APS.
15485633 Dyslipidemia associated with atherosclerotic disease systemically alters dendritic cell mo 2004 Oct High LDL and/or low HDL are risk factors for atherosclerosis and are also a common clinical feature in systemic lupus erythematosus, rheumatoid arthritis, and psoriasis. Here, we show that changes in lipid profiles that reflect atherosclerotic disease led to activation of skin murine dendritic cells (DCs) locally, promoted dermal inflammation, and induced lymph node hypertrophy. Paradoxically, DC migration to lymph nodes was impaired, suppressing immunologic priming. Impaired migration resulted from inhibitory signals generated by platelet-activating factor (PAF) or oxidized LDL that acts as a PAF mimetic. Normal DC migration and priming was restored by HDL or HDL-associated PAF acetylhydrolase (PAFAH), which mediates inactivation of PAF and oxidized LDL. Thus, atherosclerotic changes can sequester activated DCs in the periphery where they may aggravate local inflammation even as they poorly carry out functions that require their migration to lymph nodes. In this context, HDL and PAFAH maintain a normally functional DC compartment.
15300966 Does disease management improve clinical and economic outcomes in patients with chronic di 2004 Aug 1 PURPOSE: To assess the clinical and economic effects of disease management in patients with chronic diseases. METHODS: Electronic databases were searched for English-language articles from 1987 to 2001. Articles were included if they used a systematic approach to care and evaluated patients with chronic disease, reported objective measurements of the processes or outcomes of care, and employed acceptable experimental or quasi-experimental study designs as defined by the Cochrane Effective Practice and Organization of Care Group. RESULTS: Two reviewers evaluated 16,917 titles and identified 102 studies that met the inclusion criteria. Identified studies represented 11 chronic conditions: depression, diabetes, rheumatoid arthritis, chronic pain, coronary artery disease, asthma, heart failure, back pain, chronic obstructive pulmonary disease, hypertension, and hyperlipidemia. Disease management programs for patients with depression had the highest percentage of comparisons (48% [41/86]) showing substantial improvements in patient care, whereas programs for patients with chronic obstructive pulmonary disease (9% [2/22]) or chronic pain (8% [1/12]) appeared to be the least effective. Of the outcomes more frequently studied, disease management appeared to improve patient satisfaction (71% [12/17]), patient adherence (47% [17/36]), and disease control (45% [33/74]) most commonly and cost-related outcomes least frequently (11% to 16%). CONCLUSION: Disease management programs were associated with marked improvements in many different processes and outcomes of care. Few studies demonstrated a notable reduction in costs. Further research is needed to understand how disease management can most effectively improve the quality and cost of care for patients with chronic diseases.
15144121 Expression of Ro/SS-A and La/SS-B determined by immunohistochemistry in healthy, inflamed 2004 May OBJECTIVE: Autoantibodies to the ribonucleoproteins Ro/SS-A and La/SS-B are found in autoimmune diseases such as primary Sjögren's syndrome (pSS), systemic lupus erythematousus and rheumatoid arthritis. Increased and aberrant expression of Ro/SS-A and La/SS-B in target organs, which have been reported in the recent literature, might contribute to their antigenicity. However, data on the expression of Ro/SS-A and La/SS-B in other inflammatory conditions are scarce. MATERIALS AND METHODS: Using monoclonal antibodies against Ro/SS-A and La/SS-B, we studied the expression of these antigens in paraffin-embedded healthy tissue, aspecific inflamed tissue, the neonatal and adult cardiac conduction systems and labial salivary gland tissues of patients suspected of having pSS. RESULTS: In healthy tissues, the nuclei expressed both Ro/SS-A and La/SS-B. This expression was stronger in inflamed tissues. Nucleoli were negative and cytoplasmic expression was weaker than nuclear expression. No increased or aberrant expression of Ro/SS-A or La/SS-B was observed in either neonatal or adult atrioventricular nodes and bundle branches. More pSS patients showed high La/SS-B immunoreactivity levels in their labial salivary gland ductal cell nuclei than non-Sjögren's syndrome sicca patients. CONCLUSIONS: Ro/SS-A and La/SS-B expression is a generalized cell biological phenomenon and may be upregulated by increased cell activation both in aspecific and autoimmune-mediated inflammation. In pSS the high expression of La/SS-B in labial salivary, gland ductal cell nuclei might contribute to the local immune response.
15022409 [New immunological weapons for medicine in the 21st Century: biological therapy based on t 2003 Dec The fusion of a murine B cell and a myeloma cell generates a hybridoma that produces monoclonal antibody (mAb). These murine mAb induce the HAMA (human anti-mouse antibodies) response. Murine mAb have been modified by genetic engineering, producing molecules with a higher proportion of human protein. At present, chimeric, humanized and fully human mAb are available. mAb block interactions between target molecules and their ligands or trigger the lyses of mAb-coated tumor cells. Numerous mAb have been developed using the recombinant DNA technology and several are available in the market. Trastuzumab, against HER2/neu, is useful in breast cancer; rituximab, against CD20 in B lymphocytes is useful in lymphoma; alemtuzumah, against CD52 is used in lymphoma and leukemia; daclizumab and basiliximab block the IL-2 receptor interaction and reduce acute rejection in kidney transplantation; abciximab, an antagonist of GPIIb/IIIa platelet receptor, is used in patients undergoing acute coronary syndromes. In autoimmunity diseases, blocking tumor necrosis factor by infliximab and adalimumab has demonstrated excellent results. Thus, infliximab is useful in the treatment of rheumatoid arthritis (RA), Crohn's disease and ulcerative colitis while adalimumab is the first fully human mAb available for RA. Infliximab and adalimumab reduce signs and symptoms in RA and they also interfere with progression of joint damage. Finally, the direct benefits of antagonist treatment can occur at the expense of a major adverse effect in some other biological function.
14999731 Methotrexate loaded poly(L-lactic acid) microspheres for intra-articular delivery of metho 2004 Apr A controlled release delivery system that localizes methotrexate (MTX) in the synovial joint is needed to treat inflammation in rheumatoid arthritis (RA). The purpose of this work was to develop and characterize MTX loaded poly(l-lactic acid) (PLLA) microspheres and evaluate in vivo tolerability and MTX plasma concentrations following intra-articular injection into healthy rabbits. MTX loaded PLLA (2 kg/mole) microspheres were prepared using the solvent evaporation method and characterized in terms of size, molecular weight, thermal properties, and release rates into phosphate buffered saline (PBS) (pH 7.4) at 37 degrees C. Biocompatibility was evaluated by observing the swelling of the joints of the rabbits and histological analysis following the injection of the microspheres. MTX concentrations in the plasma and urine samples of rabbits were evaluated by high-performance liquid chromatography (HPLC). MTX loaded microspheres showed a rapid burst phase followed by a slow release phase. MTX loaded and control microspheres were biocompatible and plasma concentrations of MTX were tenfold higher in rabbits injected intra-articularly with free MTX than MTX microspheres. MTX microspheres may retain the drug in the joint by reducing clearance from the joint into the blood.
14965322 Clinical pharmacology of novel selective COX-2 inhibitors. 2004 Novel coxibs (i.e. etoricoxib, valdecoxib, parecoxib and lumiracoxib) with enhanced biochemical cyclooxygenase (COX)-2 selectivity over that of rofecoxib and celecoxib have been recently developed. They have the potential advantage to spare COX-1 activity, thus reducing gastrointestinal toxicity, even when administered at high doses to improve efficacy. They are characterized by different pharmacodynamic and pharmacokinetics features. The higher biochemical selectivity of valdecoxib than celecoxib, evidenced in vitro, may be clinically relevant leading to an improved gastrointestinal safety. Interestingly, parecoxib, a pro-drug of valdecoxib, is the only injectable coxib. Etoricoxib shows only a slightly improved COX-2 selectivity than rofecoxib, a highly selective COX-2 inhibitor that has been reported to halve the incidence of serious gastrointestinal toxicity compared to nonselective nonsteroidal antiinflammatory drugs (NSAIDs). Lumiracoxib, the most selective COX-2 inhibitor in vitro, is the only acidic coxib. The hypothesis that this chemical property may lead to an increased and persistent drug accumulation in inflammatory sites and consequently to an improved clinical efficacy, however, remains to be verified. Several randomized clinical studies suggest that the novel coxibs have comparable efficacy to nonselective NSAIDs in the treatment of osteoarthritis, rheumatoid arthritis and acute pain, but they share similar renal side-effects. The apparent dose-dependence of renal toxicity may limit the use of higher doses of the novel coxibs for improved efficacy. Large-size randomized clinical trials are ongoing to define the gastrointestinal and cardiovascular safety of the novel coxibs.
14871291 Regulation of the human acute phase serum amyloid A genes by tumour necrosis factor-alpha, 2004 Feb The major acute-phase protein serum amyloid A, A-SAA, is upregulated by a variety of inflammatory stimuli, including cytokines and glucocorticoids (GCs). Elevated systemic concentrations of both A-SAA and tumour necrosis factor (TNF)-alpha are a feature of inflammatory diseases, such as rheumatoid arthritis and inflammatory bowel disease. Here, we examine the roles of TNF-alpha, interleukin-6 (IL-6) and GCs on the transcriptional regulation of the two human A-SAA genes (SAA1 and SAA2) and show that these stimuli have different effects on the SAA1 and SAA2 promoters in HepG2 hepatoma and KB epithelial cell lines. Both genes are induced modestly by TNF-alpha and IL-6 alone and synergistically by TNF-alpha plus IL-6. The TNF-driven induction of SAA1, but not that of SAA2, can be enhanced by GCs in both cell lines, whereas GCs alone can upregulate SAA1 only in epithelial cells. The upregulation of both genes by cytokines, and of SAA1 by GCs, is more rapid in epithelial cells than hepatoma cells. We established that the order in which either cell line was treated with TNF-alpha and IL-6 influenced A-SAA promoter transcriptional activation. Treatment with TNF-alpha followed by IL-6 resulted in a much greater induction of both A-SAA genes than treatment with IL-6 followed by TNF-alpha.
14709417 Identification of autoantibody against poly (ADP-ribose) polymerase (PARP) fragment as a s 2004 Feb OBJECTIVES: By utilizing serological analysis of a recombinant cDNA expression library (SEREX), we previously found that autoantibodies to poly (ADP-ribose) polymerase (PARP) are specifically present in the sera of patients with SLE. In this study, recombinant proteins of various domains of PARP were used to determine the PARP domain that is associated with SLE. METHODS: We produced four recombinant PARP proteins, which contained various PARP domains, and then carried out enzyme linked immunosorbent assay (ELISA) using these recombinant proteins to identify domains useful for SLE diagnosis. The recombinant proteins used in this analysis were; ADPNF (amino acids 1-234), ET-L2 (amino acids 339-680), ET-L3 (amino acids 681-1014), and ADPCF (amino acids 300-1014). RESULT: ELISA with ADPNF or ET-L2 showed low sensitivity in the sera of patients with SLE (14.3% and 17.0% respectively), whereas ELISA with ET-L3 or ADPCF showed high sensitivity in the sera of patients with SLE (34.0% and 49.1%, respectively). Autoantibodies to ADPCF were not found in the sera of patients with rheumatoid arthritis (0/30), systemic sclerosis (0/30) or healthy donors (0/54) and were rarely found in polymyositis/dermatomyositis (1/30) and Sjogren syndrome (1/14). Autoantibodies to ADPCF were closely associated with the presence of an oral ulcer in SLE (P=0.03, by the chi-square test). CONCLUSION: The high sensitivity and specificity shown by autoantibodies to ADPCF protein could be used as a valuable serologic maker for the diagnosis of SLE.
14679827 The burden of musculoskeletal conditions at the start of the new millennium. 2003 Musculoskeletal conditions are extremely common and include more than 150 different diseases and syndromes, which are usually associated with pain and loss of function. In the developed world, where these conditions are already the most frequent cause of physical disability, ageing of the most populous demographic groups will further increase the burden these conditions impose. In the developing world, successful care of childhood and communicable diseases and an increase in road traffic accidents is shifting the burden to musculoskeletal and other noncommunicable conditions. To help better prepare nations for the increase in disability brought about by musculoskeletal conditions, a Scientific Group meeting was held to map out the burden of the most prominent musculoskeletal conditions at the start of the Bone and Joint Decade. In particular, the Group gathered data on the incidence and prevalence of rheumatoid arthritis, osteoarthritis, osteoporosis, major limb trauma and spinal disorders. Data were collected and organized by world region, gender and age groups to assist with the ongoing WHO Global Burden of Disease 2000 study. The Group also considered what is known about the severity and course of these conditions, along with their economic impact. The most relevant domains to assess and monitor the consequences of these conditions were identified and used to describe health states for the different stages of the conditions. Instruments that measure these most important domains for the different conditions were recommended. It is clear from data collated that the impact from musculoskeletal conditions and trauma varies among different parts of the world and is influenced by social structure, expectation and economics, and that it is most difficult to measure impact in less developed nations, where the predicted increase is greatest.
14607961 Inhibition of fibrocyte differentiation by serum amyloid P. 2003 Nov 15 Wound healing and the dysregulated events leading to fibrosis both involve the proliferation and differentiation of fibroblasts and the deposition of extracellular matrix. Whether these fibroblasts are locally derived or from a circulating precursor population is unclear. Fibrocytes are a distinct population of fibroblast-like cells derived from peripheral blood monocytes that enter sites of tissue injury to promote angiogenesis and wound healing. We have found that CD14(+) peripheral blood monocytes cultured in the absence of serum or plasma differentiate into fibrocytes within 72 h. We purified the factor in serum and plasma that prevents the rapid appearance of fibrocytes, and identified it as serum amyloid P (SAP). Purified SAP inhibits fibrocyte differentiation at levels similar to those found in plasma, while depleting SAP reduces the ability of plasma to inhibit fibrocyte differentiation. Compared with sera from healthy individuals and patients with rheumatoid arthritis, sera from patients with scleroderma and mixed connective tissue disease, two systemic fibrotic diseases, were less able to inhibit fibrocyte differentiation in vitro and had correspondingly lower serum levels of SAP. These results suggest that low levels of SAP may thus augment pathological processes leading to fibrosis. These data also suggest mechanisms to inhibit fibrosis in chronic inflammatory conditions, or conversely to promote wound healing.
14556316 Photochemical internalization enhances the cytotoxic effect of the protein toxin gelonin a 2003 Sep Further advantages in the treatment of soft-tissue sarcomas will only be achieved by tailoring the adjuvant therapy after surgery. The photochemically directed release of macro-molecules from endosomes and lysosomes into the cytosol is a novel technology, named photochemical internalization (PCI), that has been evaluated for treatment of sarcoma cells in vitro. Two human synovial sarcoma cell lines (SW 982 and CME-1) were treated with the photosensitizer meso-tetraphenylporphine with two sulfonate groups on adjacent phenyl rings (TPPS2a) and a plasmid encoding enhanced green fluorescent protein (EGFP) complexed to poly-L-lysine to investigate the influence of PCI on gene transfer and with 5 micrograms/mL gelonin to investigate PCI of a Type-I ribosome-inactivating protein toxin. In addition, both cell lines were transduced with an Adenovirus serotype 5 encoding the Escherichia coli lacZ gene (AdHCMV-lacZ, expressing beta-galactosidase) and treated with TPPS2a and light to evaluate the effect of PCI on the transduction rate. Photochemically induced transfection with the reporter gene EGFP in CME-1 cells increased from 0% of cells at no light to 40% of the cells after 60 s of light exposure. In contrast, the SW 982 cells showed no enhanced expression of the gene. The fraction of virally transduced cells was about doubled in both cell lines by means of PCI, although the transduction was more efficient in the CME-1 cells. Both cell lines became up to four-fold more sensitive to light when combining photochemical treatment with gelonin incubation. Our experiments showed that PCI induced the endocytic escape of therapeutic substances in cells derived from human soft-tissue sarcomas.
14519760 Generation of a recombinant, membrane-targeted form of the complement regulator CD59: acti 2003 Dec 5 Inappropriate activation of complement contributes to pathology in diverse inflammatory diseases. Soluble recombinant forms of the natural cell membrane regulators of complement are effective in animal models and some human diseases. However, their use is limited for reasons related to cost, short half lives, and propensity to cause unwanted systemic effects. Some of these limitations may be overcome by use of bacterial expression systems, specific targeting moieties, and judicious choice of regulator. Here we describe the application of these strategies to the generation of a membrane-targeted form of CD59. A recombinant soluble form of rat CD59, comprising the first 71 residues of the mature protein and missing the membrane-anchoring signal, was expressed in bacteria, purified, and refolded in a fully active form. The protein was coupled through its carboxyl terminus to a short, synthetic address tag that confers membrane binding activity. Attachment of the membrane address tag markedly increased complement-inhibitory activity assessed in vitro in hemolysis assays. Intra-articular administration of the tagged agent markedly suppressed disease in a model of rheumatoid arthritis in Lewis rats. This novel type of agent, termed sCD59-APT542, offers for the first time the prospect of efficient and specific inhibition of membrane attack complex activity in vivo.
12923767 High resolution proteome analysis of cryoglobulins using Fourier transform-ion cyclotron r 2003 Aug Cryoglobulins are cold-precipitable serum immunoglobulins associated with a number of infectious, autoimmune and neoplastic disorders such as hepatitis C, Waldenström's macroglobulinemia, multiple myeloma, chronic lymphocytic leukemia, and rheumatoid arthritis. The mechanism(s) of cryoprecipitation has remained obscure hitherto, which has prompted recent intensive efforts on the identification of cryoglobulin components. In the present study, two-dimensional gel electrophoresis (2-DE) combined with high resolution Fourier transform-ion cyclotron resonance (FT-ICR) mass spectrometry has been applied as a powerful approach for the analysis of cryoglobulins. While FT-ICR mass spectrometry has been shown to enable the high resolution identification and structure analysis of biopolymers using both electrospray (ESI) and matrix-assisted laser desorption ionization (MALDI), the recently developed MALDI-FT-ICR source is shown here to provide high (sub-ppm) mass determination accuracy and isotopic fine structure as particular advantages in the identification of proteins. The main protein components in a serum cryoprecipitate from a patient with hepatitis C virus (HCV) infection and presenting type II cryogobulinemia are immunoglobulin (Ig)M and IgG which were identified by MALDI-FT-ICR MS analysis after separation by 2-DE as mu- and gamma-heavy chains, kappa- and lambda-light chains, and J-chains. Furthermore, complementarity determining regions CDR1 and CDR2 from monoclonal IgM-RF variable region (V)L were directly identified using accurate mass determinations by FT-ICR-MS. The presence of Spalpha was ascertained as an IgM-associated protein in the serum cryoprecipitate from a patient with HCV infection.
12902784 A comparison of open reduction and internal fixation and primary total elbow arthroplasty 2003 Aug OBJECTIVE: To compare open reduction and internal fixation (ORIF) with total elbow arthroplasty (TEA) for intraarticular distal humerus fractures in women older than 65 years of age. DESIGN: Retrospective review. SETTING: Information was obtained from a Level 1 trauma center with fellowship-trained traumatologists and a tertiary care center with fellowship-trained shoulder and elbow surgeons. PATIENTS: Patients were 24 women older than age 65 who sustained distal humerus fractures that required surgical treatment with clinical follow-up at a minimum of 2 years. All fractures were OTA classification 13.C2 or 13.C3. No patients were lost to follow-up. INTERVENTION: ORIF or TEA was the treatment method. MAIN OUTCOME MEASUREMENTS: The Mayo Elbow Performance score and the need for revision surgery were established as the means of patient evaluation. RESULTS AND CONCLUSIONS: Using the Mayo Elbow Performance score, the outcomes of the 12 patients treated with ORIF were as follows: 4 excellent, 4 good, 1 fair, and 3 poor (cases that required conversion to TEA). Outcomes of the 12 patients treated with TEA were as follows: 11 excellent and 1 good. There were no fair or poor outcomes in the TEA group. No patients treated with TEA required revision surgery. We believe TEA to be a viable treatment option for distal intraarticular humerus fractures in women older than age 65. This is particularly true for women with associated comorbidities, such as rheumatoid arthritis, osteoporosis, and conditions requiring the use of systemic steroids.
12858463 Learning from pain scales: patient perspective. 2003 Jul OBJECTIVE: Rheumatologists often deal with patients' pain, as commonly measured by clinical scales. However, no published study in the last 25 years has explored patient preferences for the 2 most frequently used clinical scales the verbal rating scale (VRS) and the visual analog scale (VAS). We (1) evaluated patient preferences for the 10 cm horizontal VAS versus the 5 point VRS and identified associated reasons for their preferences; and (2) validated the test-retest reliability and construct validity of these scales. METHODS: Patients with painful rheumatological conditions rated the VAS and the VRS to assess pain intensity and stated which scale they preferred and why. Exploration of tender points and dolorimetry was performed in all cases. RESULTS: Of 113 patients in the sample, 93% were women, 85% of whom had rheumatoid arthritis. In this sample, 52.8% preferred the VRS, 28.3% the VAS, and 18.9% expressed no preference. Patients who preferred the VRS said it was easier than the VAS to understand and rate. They also reported being more comfortable using words than numbers. Patients who preferred the VAS said that numbers classified pain better and that this allowed them to be objective and precise. Patients with 0-6 years of schooling preferred the VRS, while those with > 6 years preferred the VAS. There was a significant association between the number of tender points and pain intensity with both scales, as well as between threshold and tolerance with the VAS. High correlations were found between the VAS and the VRS (r = 0.79) and between tolerance and threshold (r = 0.96). Test-retest showed a high correlation for both scales: VAS = 0.97 and VRS = 0.89. CONCLUSION: Both scales are valid measures of pain intensity. The choice should depend on the setting, the clinician's goal, and the patient's level of education. Patient preference is central to better physician-patient communication.