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ID PMID Title PublicationDate abstract
12215898 Polymorphisms of human CD19 gene: possible association with susceptibility to systemic lup 2002 Oct CD19 regulates the signaling for B lymphocyte development, activation and proliferation. In mice, CD19 deficiency and overexpression were shown to result in hypogammaglobulinemia and autoantibody production, respectively. In the present study, we screened for the polymorphisms of CD19, and examined the detected polymorphisms for the association with rheumatoid arthritis (RA), Crohn's disease and systemic lupus erythematosus (SLE). Two SNPs, c.705G>T (P235P and IVS14-30C>T, were decreased (P = 0.0096 and P = 0.028, respectively), in SLE. A GT repeat polymorphism, c.*132(GT)(12-18), was detected within the 3'-untranslated region, and individuals with > or =15 times repeat was significantly increased in the independent two groups of Japanese SLE patients (P = 0.011 and P = 0.035, respectively); the overall difference between total SLE and controls was striking (P = 0.0061). No association was observed for RA and Crohn's disease. In addition, no variations other than the common polymorphisms were detected in four patients with common variable immunodeficiency, the phenotype of which resembles CD19 deficient mice. In Caucasian SLE families, this GT repeat polymorphism was rare. CD19 mRNA level in the isolated peripheral blood B lymphocytes was lower in individuals possessing (GT)(15-18) alleles compared with those without these alleles, both in controls and in SLE patients; however, the difference did not reach statistical significance. These results suggested that either the slight reduction in the CD19 mRNA level associated with the elongation of GT repeat, or an allele of another locus in linkage disequilibrium with CD19 (GT)(15-18), may be associated with susceptibility to SLE in Japanese.
16038846 Severe pyogenic infections in patients taking infliximab: a regional cohort study. 2005 Jul OBJECTIVE: To evaluate the prevalence and risk factors of severe pyogenic infections in rheumatology patients taking infliximab in everyday practice. METHODS: Regional prospective cohort study of patients taking infliximab for rheumatoid arthritis or ankylosing spondylitis with data collection on standardized forms. The medical records of patients with severe pyogenic infections were subjected to a detailed retrospective review. Patients with and without severe pyogenic infections were compared. RESULTS: The cohort included 83 patients (55 women and 28 men). Severe pyogenic infections occurred in five (6%) patients (three women and two men), all of whom had acute or underlying risk factors. Higher values were found in these five patients for mean age (65.8 +/- 12 vs. 53.9 +/- 13 years, P = 0.04) and mean daily glucocorticoid dosage (15.5 +/- 9 vs. 6.9 +/- 7 mg/day prednisone-equivalent, P = 0.036), as compared to the other patients. CONCLUSION: Older age and high-dose glucocorticoid therapy are associated with an increased risk of severe pyogenic infection during infliximab therapy. Caution is in order when starting and monitoring infliximab therapy in patients with risk factors. Our data also emphasize the need for a careful search for risk factors before each infliximab infusion.
12730536 Can diagnostic triage by general practitioners or rheumatology nurses improve the positive 2003 Jun OBJECTIVES: To determine whether diagnostic triage by general practitioners (GPs) or rheumatology nurses (RNs) can improve the positive predictive value of referrals to early arthritis clinics (EACs). METHODS: Four GPs and two RNs were trained in the assessment of early inflammatory arthritis (IA) by four visits to an EAC supervised by hospital rheumatologists. Patients referred to one of three EACs were recruited for study and assessed independently by a GP, an RN and one of six rheumatologists. Each assessor was asked to record their clinical findings and whether they considered the patient to have IA. Each was then asked to judge the appropriateness of the referral according to predetermined guidelines. The rheumatologists had been shown previously to have a satisfactory level of agreement in the assessment of IA. RESULTS: Ninety-six patients were approached and all consented to take part in the study. In 49 cases (51%), the rheumatologist judged that the patient had IA and that the referral was appropriate. The assessments of GPs and RNs were compared with those of the rheumatologists. Levels of agreement were measured using the kappa value, where 1.0 represents total unanimity. The kappa value was 0.77 for the GPs when compared with the rheumatologists and 0.79 for the RNs. Significant stiffness in the morning or after rest and objective joint swelling were the most important clinical features enabling the GPs and RNs to discriminate between IA and non-IA conditions. CONCLUSION: Diagnostic triage by GPs or RNs improved the positive predictive value of referrals to an EAC with a degree of accuracy approaching that of a group of experienced rheumatologists.
12767262 Phospholipase A2 modulates respiratory burst developed by neutrophils in patients with rhe 2003 Jan Activated by bacterial peptides, phorbol esters, calcium ionophores and other agonists, neutrophils (PMNs) release the proinflammatory mediator, arachidonic acid (AA) via the intervention of phospholipase A(2) (PLA(2)). AA may play an essential role in activation of NADPH-oxidase, which is involved in the generation of superoxide anion by neutrophils. The present study is focused on the involvement of PLA(2) in the respiratory burst developed by PMNs isolated from patients with rheumatoid arthritis (RA). PLA(2) exists in very high levels in diseases such as rheumatoid arthritis and may cause acute inflammatory and proliferative changes in synovial structures. The respiratory burst was evaluated as superoxide anion release, using an amplified chemiluminescence method. The assays were performed using PMNs untreated or treated with different doses of stimulatory reagents (phorbol 12-myristate-13-acetate (PMA), calcium ionophore (A23187)). Our data suggested that PMA stimulated the production of superoxide anion in a dose-response manner, as compared with A23187, which did not induce a significant release of superoxide anion in PMNs-RA. The exogenous addition of AA significantly amplified the superoxide anion release by PMNs-RA stimulated with PMA and to a lesser extent, by PMNs stimulated with A23187. AA has also reversed the inhibitory effect of arachidonyl-trifluorometylketone and E-6-(bromomethylene)tetrahydro-3-(1-naphthalenyl)2H-pyran-2-one (BEL) on the superoxide anion release by PMNs-RA. In conclusion, the differential responses to these two agents suggested that different isoforms of PLA(2) were activated by A23187 or PMA, and support the idea that activation of these different PLA(2) served distinct functions of PMNs. Therefore, the inhibition of PLA(2) enzymes might be of great importance in the immunotherapy of rheumatoid arthritis.
14675564 [3H]PK11195 binding sites in human neutrophils: effect of fMLP stimulation and modulation 2004 Jan OBJECTIVE: The objectives of this study were to evaluate the [3H]PK11195 binding parameters in a model of acute inflammation, the N-formylmethionine-leucine-phenylalanine (fMLP)-stimulated neutrophil cell membranes, and to analyze if alterations of peripheral-type benzodiazepine receptor (PBR) characteristics occurred in neutrophil cell membranes of patients affected by osteoarthritis (OA), rheumatoid arthritis (RA), and psoriasic arthritis (PA). DESIGN AND METHODS: Neutrophils were obtained from 15 patients with OA, 15 patients with RA, and 15 patients with PA. fMLP stimulation was performed to aliquots of neutrophils from six healthy individuals. Evaluation of kinetic parameters of PBR was performed using [3H]PK11195, as specific radioligand compared with 15 healthy volunteers. RESULTS: The results showed a significant decrease of Kd and Bmax in fMLP-stimulated neutrophil membranes. Moreover, an increase of PBR binding sites and affinity value was observed in neutrophils membranes from PA patients. CONCLUSIONS: Our data suggested a fMLP modulation on [3H]PK11195 binding in human neutrophils. Moreover, our results showed an up-regulation of PBR in neutrophils of PA patients.
15229946 Sources of discrepancy in patient and physician global assessments of rheumatoid arthritis 2004 Jul OBJECTIVE: To investigate discrepancy in the perception of rheumatoid arthritis (RA) disease activity between patient and physician, and its possible sources. METHODS: Eighty patients with RA rated their level of disease activity on a visual analog scale (VAS). Physician global assessment (MDGA) of disease activity was performed blinded to the patient evaluation except for the results of laboratory tests. A discrepancy score (DS) was calculated by subtracting MDGA from patient global assessment (PTGA), leading to definition of 3 groups of patients: (1) no discrepancy when PTGA and MDGA were within 1.0 or 3.0 cm of each other; (2) negative discrepancy when PTGA was under-rated relative to the physician; and (3) positive discrepancy when PTGA was over-rated relative to the physician. Age, sex, disease duration, education, income, residence area, employment, use of antirheumatic drugs, comorbidity, pain score, Health Assessment Questionnaire (HAQ) rating, tender (TJC) and swollen (SJC) joint count, and Disease Activity Score (DAS28) were recorded. RESULTS: Negative discrepancy was found in 27.5% (VAS 1 cm) and 8.7% (VAS 3 cm) of patients, positive discrepancy in 43.7% (VAS 1 cm) and 23.7% (VAS 3 cm), and no discrepancy in 28.7% (VAS 1 cm) and 67.5% (VAS 3 cm). Patients were predominantly older (mean age near 50 yrs), female, with long disease duration and low income. The negative discrepancy group had a lower level of education and higher C-reactive protein (p < 0.05). The positive discrepancy group presented a higher pain score, HAQ score, and TJC (p < 0.0001). The no-discrepancy group had lower SJC (p < 0.05). CONCLUSION: Our results indicate that for disease activity in patients with RA assessed on pain score, HAQ, and TJC, the only important feature that determined perception of their RA disease activity was education.
14662854 Hypoxia-inducible factor regulates survival of antigen receptor-driven T cells. 2003 Dec 15 Peripheral T lymphocytes undergo activation by antigenic stimulation and function in hypoxic areas of inflammation. We demonstrated in CD3-positive human T cells accumulating in inflammatory tissue expression of the hypoxia-inducible factor-1alpha (HIF-1alpha), indicating a role of hypoxia-mediated signals in regulation of T cell function. Surprisingly, accumulation of HIF-1alpha in human T cells required not only hypoxia but also TCR/CD3-mediated activation. Moreover, hypoxia repressed activation-induced cell death (AICD) by TCR/CD3 stimulation, resulting in an increased survival of the cells. Microarray analysis suggested the involvement of HIF-1 target gene product adrenomedullin (AM) in this process. Indeed, AM receptor antagonist abrogated hypoxia-mediated repression of AICD. Moreover, synthetic AM peptides repressed AICD even in normoxia. Taken together, we propose that hypoxia is a critical determinant of survival of the activated T cells via the HIF-1alpha-AM cascade, defining a previously unknown mode of regulation of peripheral immunity.
12889120 [Effect of lipopolysaccharide on expression of matrix metalloproteinase-9 in human synovio 2003 Apr AIM: To study the effects of lipopolysaccharide (LPS), the supernatant of U937 cells stimulated with LPS and dexamethasone on matrix metalloproteinase-9 (MMP-9) expression in the synoviocyte from patients with rheumatoid arthritis(RA). METHODS: Fibroblast-like cells (FLS) from the joint tissue of patients with rheumatoid arthritis were cultured and incubated for 24 h with LPS (1 mg.L-1) or the supernatant of U937 cells stimulated with LPS (1 mg.L-1) for 24 h. Dexamethasone was added to the supernatant of U937 cells and FLS was incubated for 24 h. The activity of MMP-9 was analyzed by gelatin zymography. Protein expression of MMP-9 was detected by Western blot using special polyclonal antibodies. The mRNA expression of MMP-9 was detected by RT-PCR. RESULTS: The expression of MMP-9 was not markedly changed in FLS treated with LPS. The MMP-9 activity, MMP-9 secretion and MMP-9 mRNA expression were significantly increased in FLS cultured with the supernatant from U937 cell treated with LPS. Dexamethasone markedly inhibited the activity, protein secretion and mRNA expression of MMP-9 in FLS cultured with the supernatant from U937 cell stimulated with LPS, and the inhibitory effects were increased as the concentration of dexamethasone increased. CONCLUSION: LPS did not directly affect the expression of MMP-9 in FLS, but it was found to indirectly cause the increase of MMP-9 expression in FLS by stimulating U937 cell. Dexamethasone was found to inhibit this increase of MMP-9 expression.
12810970 Early results of posterior-stabilised NexGen Legacy total knee arthroplasty. 2003 Jun OBJECTIVE: To retrospectively assess the early results of the NexGen Legacy posterior-stabilised total knee prosthesis, which is a newer version of the Insall-Burstein II posterior-stabilised implant. METHODS: 48 consecutive elderly patients had 60 NexGen Legacy posterior-stabilised total knees. The mean follow-up duration was 21 months. Clinical evaluation was performed according to the Knee Society scores and a scoring system for patellofemoral articulation; radiographic assessment followed the guidelines of the Knee Society. Special emphasis was given to any patellofemoral complications, such as patellar clunk syndrome, patellar maltracking, and other disorders of the extensor mechanism. RESULTS: Only one patient had mild patellofemoral anterior knee pain at the latest follow-up; 2 patients had patellofemoral crepitus but no pain. No patellar clunk or any other complication of the patellofemoral articulation, such as patellar fracture or subluxation was found. The mean preoperative and postoperative Knee Society scores were 60 and 85 respectively. The mean postoperative knee flexion was 115 degrees. CONCLUSION: The overall early results from using the new implant were good, probably because of changes in design of the intercondylar box and its associated cam-and-post mechanism, and a more anatomic trochlea surface, so that the trochlea accommodates the natural patella.
12393721 Dysregulated lymphocyte proliferation and differentiation in patients with rheumatoid arth 2002 Dec 15 Rheumatoid arthritis (RA) is a chronic, inflammatory disease of the synovium of uncertain pathogenesis. A number of phenotypic and functional T-cell defects have been described in RA, including abnormal clonal expansions and suppressed proliferative responses, which suggest a defect in T-cell differentiation. Here, we show that RA patients possess fewer naive CD4(+) T cells than healthy controls. Furthermore, a smaller proportion of these cells contains a T-cell receptor excision circle (TREC). Patients with RA also have unusual populations of T cells. These include immature cells characterized as CD45RB(bright)CD45RA(+)CD62L(-) by flow cytometry and a large population that coexpresses CD45RA and CD45RO. These cells are hyperresponsive to mitogen and TCR stimulation when compared to naive cells. Additionally, an unusual putative central memory subset expressing CD62L, but not CD45RA, appears in RA patients at the expense of more typical cells. Levels of C-reactive protein correlate inversely with the TREC content of naive T cells and positively with the sizes of naive and immature atypical T-cell subsets. These data suggest that inflammation drives proliferation of naive T cells in RA and encourages their differentiation into atypical, hyperresponsive progeny. TREC content of individual naive and atypical T-cell subsets suggests an ontogeny consistent with this hypothesis. These studies provide further evidence of a T-cell differentiation defect in RA, which could explain some of the well-characterized immunologic features of the disease.
15343606 Treatment of fetal heart block with maternal steroid therapy: case report and review of th 2004 Sep The presence of maternal autoantibodies to SS-A/Ro and/or SS-B/La is associated with the development of fetal heart block. There are data suggesting that maternal treatment with steroids might reverse heart block. We report on a pregnancy in a mother with secondary Sjögren syndrome and systemic lupus erythematosus with presence of autoantibodies to SS-A/Ro and SS-B/La, which was complicated by the development of incomplete fetal heart block. Oral dexamethasone treatment could not prevent progression to complete heart block and was associated with a number of complications.A review of the literature revealed 19 studies (including ours) in which 93 cases of fetal heart block were treated with maternal steroid therapy. Complete heart block proved irreversible in all cases; and of 13 fetuses with incomplete heart block which received maternal steroid therapy, three had a reduction in their degree of block and one reverted to sinus rhythm. Maternal steroid therapy, initiated early in pregnancy and potentially preventing the onset of heart block, did not decrease the incidence of heart block in nine studies with 43 cases. Furthermore, the literature review revealed numerous serious side effects of maternal steroid administration during pregnancy. Data on these potential side effects are lacking in the 28 studies discussed in this review. Maternal dexamethasone therapy to prevent or treat fetal heart block remains, in our opinion, a questionable intervention and can as yet not be recommended in the clinical situation.
15496641 Unaltered etanercept pharmacokinetics with concurrent methotrexate in patients with rheuma 2004 Nov The purpose of this study was to evaluate the potential impact of concurrent weekly oral methotrexate administration on the pharmacokinetics of etanercept in patients with rheumatoid arthritis (RA) in a phase 3B trial. As part of a double-blind randomized trial of 682 patients with rheumatoid arthritis who received etanercept (25 mg subcutaneously twice weekly), methotrexate (weekly oral dose, median weekly dose: 20 mg), or etanercept (25 mg subcutaneously twice weekly) plus methotrexate (weekly oral dose, median weekly dose: 20 mg), serum etanercept concentrations were measured in a subset of patients. Serum samples for 98 randomly selected patients (48 receiving etanercept-alone treatment, 50 receiving etanercept plus methotrexate combination treatment) were analyzed to assess the pharmacokinetics of etanercept. A single blood sample was drawn from each patient at baseline and at the week 24 visit. Given the variable sampling time for patients in both groups, a population pharmacokinetic analysis using NONMEM was conducted for etanercept. A final covariate population pharmacokinetic model was constructed based on previously obtained etanercept data from both healthy subjects (n = 53) and patients with RA (n = 212) in 10 prior clinical trials. The predictive performance of the final model was assessed by both bootstrap and data-splitting validation approaches. The final model was then used to estimate Bayesian pharmacokinetic parameters for the patients in both treatments in the current trial. The potential effect of the concurrent administration of methotrexate on the pharmacokinetics of etanercept was examined by comparing the clearance values between 2 treatments using statistical criteria. A population 2-compartment model with first-order elimination from the central compartment and with either zero-order (intravenous administration) or first-order (subcutaneous administration) input was selected based on the data from the prior 10 etanercept clinical studies. The following pharmacokinetic parameters (typical value +/- standard error) were estimated: clearance (CL: 0.072 +/- 0.005 L/h), volume of distribution in the central compartment (V(c): 5.97 +/- 0.45 L), volume of distribution in the peripheral compartment (V(p): 2.05 +/- 0.32 L), intercompartment clearance (Q: 0.0645 +/- 0.0093 L/h), first-order absorption rate constant (k(a): 0.0282 +/- 0.0039 1/h), and absolute bioavailability for subcutaneous administration (F: 0.626 +/- 0.056). Interindividual variability of the pharmacokinetic parameters was quantified for CL (25.1%), V(c) (41.7%), k(a) (53.1%), and F (24.2%). Residual variability consisted of combined additive (11.4 ng/mL) and proportional error (49.9%). Both age (< 17 years) and body weight (< 60 kg) were found to be important covariates on CL. The results of both validation tests indicated the adequate predictive performance of the population model. Based on the bioequivalence criteria, the Bayesian-estimated clearance for patients receiving etanercept alone (mean: 0.070 L/h) was comparable to that for patients receiving a combination of etanercept and methotrexate (mean = 0.066 L/h). The pharmacokinetics of etanercept were not altered by the concurrent administration of methotrexate in patients with rheumatoid arthritis. Thus, no etanercept dose adjustment is needed for patients taking concurrent methotrexate.
12948524 The CC chemokine CCL20 and its receptor CCR6. 2003 Oct CCL20, alternatively named liver and activation-regulated chemokine (LARC), macrophage inflammatory protein-3alpha (MIP-3alpha) or Exodus-1, is the only chemokine known to interact with CC chemokine receptor 6 (CCR6), a property shared with the antimicrobial beta-defensins. The ligand-receptor pair CCL20-CCR6 is responsible for the chemoattraction of immature dendritic cells (DC), effector/memory T-cells and B-cells and plays a role at skin and mucosal surfaces under homeostatic and inflammatory conditions, as well as in pathology, including cancer and rheumatoid arthritis. In this review, the discovery, the gene and protein structure, the in vitro biological activities, the cell and inducer specific expression and the tissue distribution of CCL20 and CCR6 are discussed.
12847893 [The problem of rheumatoid nephropathy]. 2003 AIM: To study clinical and morphological variants and frequency of renal involvement in patients with rheumatoid arthritis (RA). MATERIAL AND METHODS: Routine laboratory tests, device (urography, dynamic scintigraphy of the kidneys) and ultrasound investigations, lifetime and postmortem examinations of renal tissue using histological, immunohistochemical and electron-microscopic techniques, biopsy of gingival and rectal mucosa for amyloid detected renal lesions in 268 (46.2%) of RA patients followed up for 25 years meeting the ARA criteria. In 98 (37%) patients renal lesions were verified morphologically. Lifetime renal biopsies were made for 60 of them. RESULTS: The diagnosis of chronic pyelonephritis was made in 117 patients, 42 patients had nephrolithlasis, nephroptosis and papillary necrosis were found in 49 and 3 patients, respectively. Arterial hypertension was present in 96 examinees, nephrotic syndrome was diagnosed in 19 and chronic renal failure--in 67 patients. Drug-related nephropathy occurred in 35 cases, in 26 cases symptoms of pyelonephritis arose prior to RA. Combination of renal diseases was found in 197 patients. Renal pathology was not verified morphologically only in 5 cases. Glomerulonephritis (GN) variants were present in 35 patients: mesangioproliferative (n = 27), membraneous (n = 5), mesangiocapillary (n = 3). 12 of them took Au preparations or D-penicillamin, therefore diagnosis of true rheumatoid GN was feasible only in 23 of them. GN was combined with renal amyloidosis (n = 28), minimal morphological changes (n = 19), interstitial/tubulointerstitial nephritis (n = 4), pyelonephritis (n = 4), arteriolosclerotic nephrosclerosis (n = 3). 41 patients with diagnosed pyelonephritis were found morphologically to have amyloidosis (n = 16), GN (n = 10), minimal morphological changes of renal tissue (n = 6), tubulointerstitial nephritis (n = 3), pyelonephritis, pyelonephritis alone (n = 4). CONCLUSION: The above morphological findings point to high occurrence of renal pathology in RA. In many cases morphological signs are more serious than clinical symptoms. If RA activity is not controlled, nephritis of any type may transform into amyloidosis. When it is impossible to formulate morphological diagnosis in RA patients, it is proposed to use the term "nephropathy". Unrelated to RA nephropathy's diagnosis is valid in cases when renal pathology manifested before RA. Renal diseases arising in the presence of RA may be associated with this disease and should be reflected in its classification.
12115397 Incidence of cancer among patients with knee implants in Sweden, 1980-1994. 2002 Jun 1 BACKGROUND: As knee implants become more common, it is important to study their potential health risks. We investigated cancer occurrence in a nationwide population-based cohort of 30,011 patients who underwent knee replacement surgery in Sweden from 1980 to 1994. METHODS: Patients were followed from 1 year after the date of their surgery through December 31, 1995, accruing 122,616 person-years of observation. The average follow-up time was 4.3 years, with 2365 patients followed for 10 years or more. RESULTS: Overall cancer incidence was not elevated compared with the general population of Sweden (standardized incidence ratio [SIR] = 1.03; 95% confidence interval [CI] = 0.98-1.08). A reduced rate for all respiratory cancers (SIR = 0.73; 95% CI = 0.59-0.91) and for lung cancer (SIR = 0.73; 95% CI = 0.58-0.91) was found among both men and women. Elevated rates were found for prostate (SIR = 1.20; 95% CI = 1.06-1.34) and bone cancer (SIR = 6.00; 95% CI = 1.24-17.52) in men. The bone cancer excess was based on three observed cases, two of which occurred at a site unrelated to the implant and the site of the third tumor is unknown. Rates of connective tissue cancer and leukemia-lymphoma were not elevated significantly among knee implant recipients. Long-term follow-up (>or= 10 years) did not show a significant excess risk for all cancer (SIR = 1.10; 95% CI = 0.86-1.38) or for any site-specific cancer, including bone cancer, lymphoma, or leukemia. Subgroup analyses for patients with rheumatoid arthritis produced results similar to the overall results. CONCLUSIONS: This epidemiologic study of cancer risk among patients with knee implants is the largest to date. It provides evidence that the incidence of cancer among patients with knee implants is similar to that of the general population. Continued follow-up of this cohort is warranted to evaluate further potential long-term effects of these implants.
12883354 Confocal microscopy in ocular chrysiasis. 2003 Aug PURPOSE: To describe the presence of gold salt deposits in the corneal tissue of a patient treated with gold sodium thiomalate through confocal microscopy and to relate our findings to temporary corneal dynamics. METHODS: A patient who had been treated with gold sodium thiomalate for 6 years was referred from the Rheumatology Unit of our center for an ophthalmologic examination. At the time of examination she had been treatment-free for 9 years. Besides visual acuity, the examination included slit-lamp biomicroscopy, intraocular pressure, and fundoscopy. Confocal microscopy performed using a Confoscan P4 instrument with a 40x lens to obtain 15 images per second on an S-VHS video system (Panasonic) for subsequent analysis. RESULTS: The basic layered structure of the cornea was unaffected, but the presence of highly reflective particles was noted. These particles were interpreted as gold deposits in the corneal stroma, especially in the anterior and middle stroma. CONCLUSION: Confocal microscopy is a useful method of evaluating the deposition of gold salts in tissues, particularly the cornea. Its future use will help gain a deeper understanding of corneal metabolism.
12525998 Pulmonary hypertension associated with connective tissue disease. 2002 Nov Pulmonary arterial hypertension is a life threatening complication of several connective tissue diseases including scleroderma (both diffuse and limited scleroderma, or the CREST syndrome--calcinosis cutis, Raynaud's phenomenon, esophageal dysfunction, sclerodactyly, and telangectasia), systemic lupus erythomatosis (SLE), mixed connective tissue disease (MCTD), and less commonly, rheumatoid arthritis (RA) and dermatomyositis/polymyositis. This report reviews the occurrence of this complication, potential etiologies, clinical presentation, and treatment options.
12747268 Low-dose glucocorticoids in early rheumatoid arthritis: discordant effects on bone mineral 2003 Mar OBJECTIVE: To investigate the incidence of osteoporotic fractures and effects on bone of low-dose glucocorticoid (GC) monotherapy in a group of previously untreated patients with early active RA we performed a double blind, randomised, placebo-controlled clinical trial. The study duration was 2 years, with an open follow-up during the third year. Patients were randomly allocated to receive 10 mg prednisone or placebo. METHODS: Non-steroidal anti-inflammatory drugs (NSAIDs) were allowed in both groups. After 6 months sulphasalazine (2 gr daily) could be prescribed as rescue therapy in both groups. Except for 500 mg calcium supplement daily, no specific preventive measures were taken. This was a normal procedure at the time the study was designed (1989-1991). At the start of the study and every 6 months, X-rays of the twelfth thoracic and of all lumbar vertebrae were scored using the Kleerekoper method, and every year biochemical parameters of bone metabolism and bone mineral density (BMD, expressed in T-scores) and bone mineral content (BMC, expressed in g/cm) were assessed. RESULTS: In the prednisone group there was a higher incidence during the study of lumbar vertebral fractures than in the placebo group: 7 vs 4 respectively. This difference did not reach statistical significance however, probably because of the small numbers. One patient of the prednisone group suffered an osteoporotic fracture of the pelvis. In the 2-year study and the subsequent follow-up year, no other peripheral fractures were seen in either group. No significant changes from baseline in BMD and BMC of the hips were seen in either group during the study and the follow-up year. In the lumbar spine, BMD in the prednisone group decreased although not statistically significantly during the whole study. No correlation between changes in serum osteocalcin and BMD was observed. CONCLUSION: Low-dose prednisone monotherapy for patients with early active previously untreated RA seems to increase the risk of fractures not only by reducing the BMD but also by changes in bone strength and structure.
12219632 [Technique and value of arthrosonography in rheumatologic diagnosis--3: Ultrasound diagnos 2002 Jun The clinical investigation of ankles, feet, and toes is frequently equivocal in rheumatology. Sonography can distinguish between underlying pathologies. We suggest following standard scans: 1) anterior longitudinal scan to diagnose effusions in the ankle and talonavicular joints, to display erosive and osteoarthrotic pathologies, and to diagnose tenosynovitis of the extensor tendons; 2) anterior transverse scan to document the findings in an additional dimension; 3) lateral transverse scan and 4) lateral longitudinal scan to diagnose tenosynovitis of the peroneus tendons; 5) medial transverse scan and 6) medial longitudinal scan to diagnose tenosynovitis of the flexor tendons; 7) posterior longitudinal scan and 8) posterior transverse scan to evaluate the Achilles tendon, the retrocalcaneal bursa, and the posterior recess of the ankle joint. Additionally we suggest optional scans: 9) plantar longitudinal scan for the plantar fascia and the plantar calcaneal surface; 10) distal anterior longitudinal scan to evaluate the midtalar joints; 11) distal anterior longitudinal scan to evaluate the toes; and 12) plantar, distal transverse scan to evaluate the flexor tendons of the toes. Additionally, the correlating longitudinal and transverse scans can be used to confirm the findings. The frequency of the transducer should be about 7.5 MHz for ankles and the peroneus, flexor, and extensor tendons. Ten to over 20 MHz are possible for more superficially located structures. Using modern equipment with higher resolution a hypoechoic border may be normal up to 3 mm in the ankle joints, the MTP joints, and around the peroneus tendons, and up to 4 mm around the tibialis posterior tendons.
12568929 Inhibition of cryogelation by the novel synthetic peptide (Gly-Arg-Lys-Lys-Thr): recogniti 2003 Jan 15 Cryogel is a physical gel formed by the heterophilic aggregation of extra domain A (EDA) containing fibronectin [EDA(+)FN], plasma fibronectin (pFN), fibrinogen (Fbg) and heparin (Hep) in the blood of rheumatoid arthritis (RA) patients. In cryogelation EDA(+)FN cross-links to form an interaggregate of cryogel with Hep. In the present study, we determined the recognition structure of Hep for EDA(+)FN by using oligo- and desulfonated-Hep. The affinity constant (KA) (1.2 x 10(8) per M) of oligo-Hep for EDA(+)FN did not change with a decrease in number-average molecular weight (4.9 x 10(4)-->6.0 x 10(3)). The KA-value of desulfonated-Hep for EDA(+)FN decreased from 3.2 x 10(8) to 1.0 x 10(7) per M with a decrease in the sulfonation ratio (7.0-->4.3%). We also determined the recognition structure of EDA(+)FN for Hep by an inhibition experiment on the heparin binding domain II (HepII) in EDA(+)FN with the synthetic peptides, Arg-Arg-Ala-Arg (RRAR), Asp-Gln-Ala-Arg (DNAR), Ile-Lys-Tyr-Glu-Lys (IKYEK), and Gly-Arg-Lys-Lys-Try (GRKKT). The GRKKT sequence clearly inhibited bonding between EDA(+)FN and Heps containing oligo- and desulfonated-Hep. The amount of cryogel formed in the RA-patient model plasma corresponded to the EDA(+)FN concentration in cryogel (36.7%) normalized by the EDA(+)FN concentration in plasma. When GRKKT was added to plasma, the EDA(+)FN concentration fell to 10.5%. These results demonstrated that inhibition of cryogelation in plasma could progress to a novel treatment for RA.