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ID PMID Title PublicationDate abstract
15351043 A rapid and simple determination of A77 1726 in human serum by high-performance liquid chr 2004 Sep 21 Leflunomide is a disease-modifying antirheumatic drug, which is bioactivated by formation of A77 1726. In this study a rapid and simple quantitative assay using a reversed phase HPLC-UV method is validated for detection of A77 1726 in human serum. The HPLC-UV method uses a mobile phase consisting of methanol and a KH2PO4-buffer (45 mM, pH = 3) (50:50,v/v), at a flow rate of 1 mL/min. A77 1726 is detected by UV-absorption at 295 nm with a retention time of 8.9 min. Demoxepam is used as internal standard. Validation showed lower and upper limits of quantitation of 0.5 and 100 mg/L, respectively. The assay was linear over the concentration range of 0.5-100 mg/L (r2 > 0.999). Intra- and inter-day precision showed coefficients of variation within 15% over the complete concentration range; accuracy was within 8%. Commonly prescribed drugs to treat rheumatoid arthritis like disease-modifying antirheumatic drugs, analgesics and corticosteroids, and their main metabolites, are separated from A77 1726 with a resolution >2. Serum levels of A77 1726 in 37 patients on leflunomide therapy were determined using this HPLC-UV method. Measured serum A77 1726 serum concentrations in patient samples showed large variability with a range of 3-176 mg/L.
15106941 Scleral structure, organisation and disease. A review. 2004 Mar Although disease of the sclera is unusual, when it occurs it can rapidly destroy both the eye and vision. However, normally the sclera provides an opaque protective coat for the intraocular tissues and a stable support during variations in internal pressure and eye movements, which would otherwise perturb the visual process through distortion of the retina and the lens/iris diaphragm. This stability, which is vital for clear vision is made possible by the organisation and viscoelastic properties of scleral connective tissue. Microscopically, the sclera displays distinct concentric layers including, from outside, Tenon's capsule, episclera, the scleral stroma proper and lamina fusca, melding into underlying choroid. Two sites exhibit specialised structure and function: the perilimbal trabecular meshwork, through which aqueous filters into Schlemm's canal, and the lamina cribrosa, which permits axons of the optic nerve to exit the posterior sclera. Throughout, sclera is densely collagenous, the stroma consisting of fibrils with various diameters combining into either interlacing fibre bundles or defined lamellae in outer zones. Scleral fibrils are heterotypic structures made of collagen types I and III, with small amounts of types V and VI also present. Scleral elastic fibres are especially abundant in lamina fusca and trabecular meshwork. The interfibrillar matrix is occupied by small leucine-rich proteoglycans, decorin and biglycan, containing dermatan and dermatan/chondroitin sulphate glycosaminoglycans, together with the large proteoglycan, aggrecan, which also carries keratan sulphate sidechains. Decorin is closely associated with the collagen fibrils at specific binding sites situated close to the C-terminus of the collagen molecules. Proteoglycans influence hydration, solute diffusion and fluid movement through the sclera, both from the uvea and via the trabecular meshwork. As the sclera is avascular, nutrients come from the choroid and vascular plexi in Tenon's capsule and episclera, where there is an artery to artery anastomosis in which blood oscillates, rather than flows rapidly. This predisposes to the development of vasculitis causing a spectrum of inflammatory conditions of varying intensity which, in the most severe form, necrotising scleritis, may destroy all of the structural and cellular components of the sclera. Scleral cells become fibroblastic and the stroma is infiltrated with inflammatory cells dominated by macrophages and T-lymphocytes. This process resembles, and may be concurrent with, systemic disease affecting other connective tissues, particularly the synovial joints in rheumatoid arthritis. Current views support an autoimmune aetiology for scleritis. Whilst the role of immune complexes and the nature of initial pro-inflammatory antigen(s) remain unknown, the latter may reside in scleral tissue components which are released or modified by viral infection, injury or surgical trauma.
15013079 New insight into the mechanism of hip prosthesis loosening: effect of titanium debris size 2004 Mar The incidence of rheumatoid arthritis and osteoarthritis is on the rise due to our expanding elderly population. Total joint arthroplasty is the most successful, prevalent treatment modality for these and other degenerative hip conditions. Despite the wide array of prosthetic devices commercially available, hip prostheses share a common problem with a gradual and then accelerating loss of bone tissue and bone-implant interface integrity, followed by implant instability and loosening. Implant failure is largely the result of inevitable wear of the device and generation of wear debris. To provide information for the development of improved prosthetic wear characteristics, we examined the effects of size-separated titanium particles on bone forming cell populations. We demonstrate unequivocally that particle size is a critical factor in the function, proliferation, and viability of bone-forming osteoblasts in vitro. In addition, we have elucidated the time-dependent distribution of the phagocytosed particles within the osteoblast, indicating an accumulation of particles in the perinuclear area of the affected cells. The report finds that particle size is a critical factor in changes in the bone formation-related functions of osteoblasts exposed to simulate wear debris, and that 1.5-4 microm titanium particles have the greatest effect on osteoblast proliferation and viability in vitro. The size of titanium particles generated through wear of a prosthetic device may be an important consideration in the development of superior implant technology.
14761932 Reduced GRK2 level in T cells potentiates chemotaxis and signaling in response to CCL4. 2004 May Chemokine receptors belong to the family of G-protein-coupled receptors (GPCR). Phosphorylation of GPCR by GPCR kinases (GRKs) is considered to play an important role in desensitization of these receptors. We have recently shown in patients with rheumatoid arthritis that the level of GRK2 in lymphocytes is reduced by approximately 50%. However, the physiological relevance of reduced GRK2 levels in lymphocytes is not known. Here, we investigated whether reduced GRK2 expression changes the chemotactic response of T cells to the chemokines CCL3, CCL4, and CCL5. Activated T cells from GRK2+/- mice, which have a 50% reduction in GRK2 protein levels, showed a significant 40% increase in chemotaxis toward the CCR5 ligand CCL4. In addition, chemotaxis toward the CCR1 and CCR5 ligands CCL3 and CCL5 was also increased. Binding of CCL4 to activated T cells from GRK2+/- and wild-type (WT) mice was similar, but agonist-induced CCR5 phosphorylation was attenuated in GRK2+/- cells. Moreover, the calcium response and phosphorylation of protein kinase B and extracellular-regulated kinase in response to CCL4 were significantly increased in GRK2+/- T cells, showing that signaling is increased when the level of GRK2 is reduced. GRK2+/- and WT cells do become refractory to restimulation with CCL4. In conclusion, a 50% decrease in T cell GRK2 expression results in increased responsiveness to CCL3, CCL4, and CCL5, suggesting that the 50% reduction in lymphocyte GRK2 level as observed during inflammation can have functional consequences for the response of these cells to chemokines.
14679311 Advanced glycation end products in clinical nephrology. 2004 As a result of oxidative and carbonyl stress, advanced glycation end products (AGEs) are involved in the pathogenesis of severe and frequent diseases and their fatal vascular/cardiovascular complications, i.e. diabetes mellitus and its complications (nephropathy, angiopathy, neuropathy and retinopathy, renal failure and uremic and dialysis-associated complications), atherosclerosis and dialysis-related amyloidosis, neurodegenerative diseases, and rheumatoid arthritis. They are formed via non-enzymatic glycation which is specifically enhanced through the presence of oxidative and carbonyl stress, and their ability to form glycoxidation products in peptide and protein structures finally modulating or inducing biological reactivity. Food can be another source of AGEs; however, high serum AGEs in hemodialysis patients might reflect nutritional status better. Several methods of renal replacement therapy have been studied in connection with the AGE removal, but unfortunately the possibilities are still unsatisfactory even if high flux dialysis, hemofiltration, or hemodiafiltration give better results than conventional low flux dialysis. AGEs are currently being studied in the patients on peritoneal dialysis as their precursors can be formed in the dialysis fluid. AGEs can cause damage to the peritoneum and so a loss of ultrafiltration capacity. Many compounds give promising results in AGE inhibition (inhibition of formation of AGEs, inhibition of their action or degradation of AGEs), are tested for these properties, and eventually undergo clinical studies (e.g. aminoguanidine, OPB-9195, pyridoxamine, antioxidants, N-phenacylthiazolium bromide, antihypertensive drugs, angiotensin-converting enzyme inhibitors and angiotensin II receptor-1 antagonists).
14638701 Inhibition by triptolide of IL-1-induced collagen degradation by corneal fibroblasts. 2003 Dec PURPOSE: Extracts of the herb Tripterygium wilfordii hook f, the major component of which is triptolide, have been used in traditional Chinese medicine for the treatment of rheumatoid arthritis. Triptolide also exerts many other biological actions both in vitro and in vivo. The effect of this agent on collagen degradation by cultured corneal fibroblasts was examined. METHODS: Rabbit corneal fibroblasts were cultured in three-dimensional gels of type I collagen and in the absence or presence of interleukin (IL)-1beta or triptolide. The extent of collagen degradation was determined by measurement of the amount of hydroxyproline generated by acid-heat hydrolysis of the culture supernatants. The activities of matrix metalloproteinase (MMP)-1 and plasmin were measured with the specific substrates thiopeptolide and S-2251, respectively. The release of MMPs into the culture supernatant was assessed by immunoblot analysis and gelatin zymography, and the abundance of MMP mRNAs in the cells was determined by reverse transcription and real-time polymerase chain reaction. RESULTS: Triptolide inhibited the IL-1beta-induced degradation of collagen by corneal fibroblasts in a dose- and time-dependent manner. Neither the activity of purified recombinant MMP-1 nor that of plasmin in culture supernatants was affected by triptolide. The IL-1beta-induced expression of MMP-1, -2, -3, and -9 by corneal fibroblasts was inhibited by triptolide at the protein or mRNA level. CONCLUSIONS: Triptolide inhibits collagen degradation by corneal fibroblasts by inducing downregulation of the production of MMPs, without directly affecting the collagenolytic activity of these enzymes.
12906870 The effect of etanercept and infliximab on the production of tumour necrosis factor alpha, 2003 Aug 7 BACKGROUND/AIMS: Infliximab (Ifx) is effective in the treatment of Crohn's disease (CD) and rheumatoid arthritis (RA), etanercept (Eta) in RA but not in CD. The mechanisms underlying these clinical differences are not fully understood, but this knowledge could be valuable to identify responders and develop new treatments. This study compares Eta and Ifx in vitro regarding transmembrane tumour necrosis factor alpha (tmb-TNF-alpha) expression and interferon-gamma (IFN-gamma), TNF-alpha and granulocyte macrophage colony stimulating factor (GM-CSF) production in intestinal T lymphocytes. METHODS: T lymphocyte cultures were established from biopsies from 10 CD patients and three healthy controls. The cytokine production and the expression of tmb-TNF-alpha were measured in the presence of Ifx/Eta. RESULTS: Eta and Ifx downregulated the production of IFN-gamma and GM-CSF in colonic T lymphocytes from CD patients and healthy controls. Both drugs bound tmb-TNF-alpha on activated T lymphocytes besides neutralising TNF-alpha, Eta less efficiently than Ifx (406 pg/ml (337-475); 133 pg/ml (119-147); p=0.004). TNF-alpha was detectable with the present assay in cell lines cultured in the presence of excess Eta. CONCLUSIONS: We have established that Eta is just as efficient as Ifx in downregulating IFN-gamma and GM-CSF production in vitro and Eta bound to tmb-TNF-alpha. However, Eta bound the TNF-alpha molecule, important in CD, less efficiently than Ifx.
12842452 Distinct gene expression of osteopontin in patients with ulcerative colitis. 2003 May 1 BACKGROUND: Ulcerative colitis (UC) is a multifactorial disorder of unknown etiology. Few studies have applied genome-wide gene expression analysis in colon tissue samples of UC. We report the analysis of mucosal gene expression in UC and noninflamed control specimens. MATERIALS AND METHODS: This study included 7 UC patients who received a total colectomy because of severe total colitis. Normal control colon tissues were obtained at least 10 cm from the area of pathology in 3 colon cancer patients. Ten colonic tissue samples (7 UC and 3 normal control samples) were subjected to high-density oligonucleotide array analysis. To compare differences in the level of gene expression between UC and control samples, Mann-Whitney U-test was used, with significance set at P < 0.05. RESULTS: Twenty-five genes had a 3.0 approximately 23.4-fold higher mRNA expression in UC samples compared with normal samples, whereas three genes had a 3.0 approximately 3.4-fold lower expression in UC samples compared with normal samples. Two genes showing more than a 10-fold increase expression in UC samples were a macrophage metalloelastase (L23808) and a osteopontin (AF052124). It has been said that macrophage metalloelastase is related to ulcer formation of the intestine, whereas osteopontin plays an important role in the pathogenesis of systemic lupus erythematosus and rheumatoid arthritis. CONCLUSION: Our present study supports the previous report that macrophage metalloelastase is related to ulcer formation of UC, and it also indicates the possibility that osteopontin plays an important role in the pathogenesis of UC via increased immune activity.
12763679 Anti-cytokine therapeutics and infections. 2003 Jun 1 In view of the increasing use of anti-cytokine-based therapies to treat autoimmune diseases, the role of specific cytokines in host defense against infection has become a highly relevant area of investigation. There are over 300,000 patients worldwide being treated with agents that specifically block the biological activities of interleukin-1 (IL-1) or tumor necrosis factor (TNF) for reducing the severity of autoimmune diseases such as rheumatoid arthritis, Crohn's disease or psoriasis. Those patients receiving anti-TNF-alpha or IL-1 blocking therapies are treated on a chronic basis. Studies suggest that other chronic inflammatory diseases will benefit from anti-cytokine therapies. However, there is a growing body of clinical evidence that neutralization of TNF-alpha is associated with an increased risk of opportunistic infections, including mycobacterial diseases. Blockade of IL-1 activity with the IL-1 receptor antagonist (IL-1Ra) appears, at present, to be relatively safe. However, because of physician under reporting (some estimates of reporting being less than 5% of these infections), the true incidence of infections, both serious and non-serious, will remain unknown. Does the increase in infections associated with anti-cytokine-based therapies come as a surprise? Of the two components of host defense, the innate and the acquired responses, which are affected by anti-cytokine therapies? From a wealth of rodent studies using live infection models, the following conclusions can be drawn: (1) neutralization or gene deletion for TNF-alpha is frequently associated with reduction of host defense in models of live Gram-positive or Gram-negative infections as well as infection by intracellular microbes such as Salmonella and Listeria; (2) absence of the IL-1 receptor can also result in decreased resistance to Listeria or Gram-positive bacteria and (3) TNF-alpha and IFN-gamma are required for defense against infection caused by Mycobacterium tuberculosis.
12730088 Effects of cyclooxygenases inhibitors on vasoactive prostanoids and thrombin generation at 2003 Jun 1 OBJECTIVE: Balance between vasoactive prostanoids that contribute to homeostasis of the circulatory system can be affected by cyclooxygenases inhibitors. Results of a recent large clinical trial show that myocardial infarction was more frequent among patients with rheumatoid arthritis treated with the selective cyclooxygenase-2 inhibitor rofecoxib compared with those treated with naproxen. Whether this difference was attributable to deleterious cardiovascular effects of rofecoxib or cardioprotective effects of naproxen has not been determined. We tested the hypothesis that naproxen, contrary to rofecoxib, exerts antithrombotic effects. METHODS AND RESULTS: Forty-five healthy men were randomized to receive a 7-day treatment with rofecoxib (50 mg/d), naproxen (1000 mg/d), aspirin (75 mg/d), or diclofenac (150 mg/d). Formation of thromboxane, prostacyclin, and thrombin in the bleeding-time blood at the site of standardized microvascular injury was assessed before and after treatment. Naproxen, like aspirin, caused significant reduction of both thromboxane and prostacyclin, whereas diclofenac depressed prostacyclin synthesis but had no effect on tromboxane formation. Naproxen and aspirin significantly suppressed thrombin generation. Diclofenac showed a similar tendency, which did not reach statistical significance. Rofecoxib had no effect on any variables measured. CONCLUSIONS: In healthy men, naproxen exerts an antithrombotic effect at least as potent as aspirin, whereas rofecoxib does not affect hemostatic balance.
12593604 Perspective of cytokine regulation for periodontal treatment: fibroblast biology. 2003 Jan Efforts to understand the pathogenesis of periodontal diseases have been underway for decades. Studies of immunological aspects in addition to the structural components of gingival fibroblasts showed that the fibroblasts actively participate in immune and inflammatory events in periodontal diseases. Future strategies for the prevention and treatment of periodontal diseases should biologically regulate fibroblast activities. These cells are surrounded by monocyte-derived proinflammatory cytokines such as interleukin-1 beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), and lymphocyte-derived interleukin-6 (IL-6) in inflamed gingival tissue. Recent anti-cytokine therapy for inflammatory diseases including rheumatoid arthritis aimed to inhibit the binding of cytokines to targeted cells such as fibroblasts and condrocytes. IL-1beta and TNF-alpha are thought to be therapeutic targets because these cytokines are essential for the initiation of inflammatory immune reactions and are produced for prolonged periods in inflammatory diseases. IL-6 is also a target, because it is abundantly present in inflammatory lesions and activates fibroblasts in the presence of soluble IL-6 receptor. In addition, these cytokines accelerate gingival fibroblasts to produce collagenolytic enzymes, resulting in tissue destruction. Soluble receptors for IL-1beta and TNF-alpha are suggested to be candidates for therapeutic molecules, but soluble receptor for IL-6 is suggested to be a factor-stimulating fibroblast. This paper will review the utilization of soluble receptors specific to inflammatory cytokines which potentially stimulate fibroblasts to regulate biological events involved in the pathogenesis of periodontal diseases.
12589974 Altered glycosylation of alpha1-acid glycoprotein in patients with inflammation and diabet 2003 Mar BACKGROUND: In certain pathophysiological conditions, such as inflammation rheumatoid arthritis and diabetes mellitus (DM), alterations in asparagine-linked glycan (N-glycan) patterns of the acute-phase protein, alpha(1)-acid glycoprotein (AGP), have been reported. In this study, we investigated N-glycan structures of AGP purified from the sera of patients with acute inflammation (n=5), type 2 diabetes mellitus (n=5), and healthy individuals (n=5). METHODS: N-Glycans were released with peptide N-glycosidase F (PNGase F) from denatured AGP and purified with cellulose cartridge. N-glycans were analyzed by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOFMS) in combination with exoglycosidase digestion. RESULTS: We revealed increases in bi-antennary complex glycans and in alpha1-3 fucosylated bi-, tri-, and tetra-antennary glycans and a decrease in tri-antennary glycans in inflammation patients. These results support increases in bindings to concanavalin A (ConA) and Aleuria aurantia lectins (AALs). In diabetic patients, the pathogenesis-specific change in N-glycan patterns of AGP was not significant. CONCLUSIONS: The MALDI-TOFMS method is sensitive and suitable for profiling analysis of N-glycans in clinical samples.
12568630 Immunosuppressive and anti-inflammatory mechanisms of triptolide, the principal active dit 2003 Extracts of Tripterygium wilfordii hook. f. (leigong teng, Thundergod vine) are effective in traditional Chinese medicine for treatment of immune inflammatory diseases including rheumatoid arthritis, systemic lupus erythematosus, nephritis and asthma. Characterisation of the terpenoids present in extracts of Tripterygium identified triptolide, a diterpenoid triepoxide, as responsible for most of the immunosuppressive, anti-inflammatory and antiproliferative effects observed in vitro. Triptolide inhibits lymphocyte activation and T-cell expression of interleukin-2 at the level of transcription. In all cell types examined, triptolide inhibits nuclear factor-kappaB transcriptional activation at a unique step in the nucleus after binding to DNA. Further characterisation of the molecular mechanisms of triptolide action will serve to elucidate pathways of immune system regulation.
12475802 Roles for insulin-like growth factor I and transforming growth factor-beta in fibrotic lun 2002 Dec Idiopathic pulmonary fibrosis (IPF) is a lung disease that is characterized by epithelial cell damage and areas of denuded basement membrane resulting in inflammation, fibroblast proliferation, excessive extracellular matrix (ECM) deposition, and remodeling of alveolar gas exchange units. The progressive loss of lung gas exchange units in patients with IPF leads to respiratory failure and eventually to death. While the etiology of this disease is unknown, for many years studies suggested that chronic inflammation was the underlying factor that caused fibroproliferation and structural alterations of the lung. Recent data show that fibroproliferation and fibrosis can occur independently of inflammation, suggesting that IPF is a disease caused by a mesenchymal, rather than an immune disorder. Mesenchymal growth factors, including transforming growth factor (TGF)-beta, insulin-like growth factor (IGF)-I, platelet-derived growth factor, connective tissue growth factor, fibroblast growth factors, and keratinocyte growth factors, as well as proinflammatory cytokines such as tumor necrosis factor-alpha and interleukin-1beta, have been shown to be exaggerated in several fibrotic lung disorders including IPF, ARDS, sarcoidosis, and bronchopulmonary dysplasia, as well as pulmonary manifestations of systemic diseases such as rheumatoid arthritis or progressive systemic sclerosis (scleroderma). We argue that inflammation is required to initiate growth factor production and repair of the damaged alveolar epithelial lining in fibrotic lung diseases and that exaggerated TGF-beta production may be responsible for the fibrotic response seen in diseases such as IPF. We recognize the potential role of several growth factors in the fibroproliferative process in the lung, and in this brief report we focus on the possible roles of the growth factors IGF-I and TGF-beta in cell migration, proliferation, and ECM synthesis in patients with IPF.
23115806 (68)Ga-1,4,7-Triazacyclononane-1,4,7-triacetic acid-c(RGDyK)-S-S-CPLHSpT. 2004 Integrins are a family of heterodimeric glycoproteins on cell surfaces that mediate diverse biological events involving cell–cell and cell–matrix interactions (1). Integrins consist of an α and a β subunit and are important for cell adhesion and signal transduction. The α(v)β(3) integrin is the most prominent receptor affecting tumor growth, tumor invasiveness, metastasis, tumor-induced angiogenesis, inflammation, osteoporosis, and rheumatoid arthritis (2-7). Expression of the α(v)β(3) integrin is strong on tumor cells and activated endothelial cells, whereas expression is weak on resting endothelial cells and most normal tissues. The peptide sequence Arg-Gly-Asp (RGD) has been identified as a recognition motif used by extracellular matrix proteins (vitronectin, fibrinogen, laminin, and collagen) to bind to a variety of integrins, including α(v)β(3). Polo-like kinase 1 (PLK1) regulates cell cycle progression during mitosis (8) and is overexpressed in many different tumors (9). The kinase activity of PLK1 is regulated by a highly conserved C-terminal polo-box domain (PBD) (10). The phosphopeptide Pro-His-Ser-p-Thr (PLHSpT) is a potent selective inhibitor of the PBD of human PLK1. However, PLHSpT does not permeate cell membranes. Binding of PLHSpT to PBD by microinjection into cancer cells induces mitotic arrest and apoptotic cell death. Kim et al. (11) designed and synthesized cRGDyK-S-S-CPLHSpT for tumor treatment and imaging of PLK1. CPLHSpT was delivered to the PLK1 in the nucleus by internalization of cRGDyK-S-S-CPLHSpT via binding of cRGDyK to the integrin receptor and cleavage of cRGDyK-S-S-CPLHSpT in the cytoplasm. For positron emission tomography (PET) imaging, (68)Ga-1,4,7-triazacyclononane-1,4,7-triacetic acid-(cRGDyK)-S-S-CPLHSpT ((68)Ga-NOTA-cRGDyK-CPLHSpT) was evaluated in nude mice bearing human glioblastoma U87MG tumors.
12510071 [Analysis of the causes of failure in carpal tunnel syndrome surgery and the results of re 2002 OBJECTIVES: We investigated the causes of failure and ensuing problems and findings in patients with unrelieved or recurrent carpal tunnel syndrome (CTS) and evaluated the results of revision surgery. METHODS: The study included 26 patients (21 women, 5 men; mean age 52 years; range 30 to 71 years) who underwent reoperation for unrelieved or recurrent symptoms following at least a year (range 1 to 4 years) after the initial surgery. A total of 34 operations had been carried out in 31 hands. All patients were investigated clinically and electrophysiologically. The mean follow-up after reoperation was 19 months (range 12 to 38 months). RESULTS: The diagnosis was confirmed in all patients by clinical and electrophysiologic studies. The primary operations had been performed using 11 transverse incisions, three incisions confined proximally to the wrist crease, 10 incisions without insufficient distal extension, and seven appropriate incisions. The transverse carpal ligament release was inadequate in 23 hands; it had not been released in three hands at all. Excessive fibrous tissue developed in one patient, leading to complete bilateral median nerve compression. Bilateral and unilateral tenosynovitis resulting from rheumatoid arthritis and tuberculosis was detected in two patients, respectively. All patients underwent repeat open carpal tunnel release. Neurolysis and tenosynovectomy were performed in both hands of one patient and in one hand of two patients, respectively. Clinical results were excellent in 24 hands, good in six hands, and fair in one hand. CONCLUSION: Selection of appropriate incision and achievement of complete carpal tunnel release without any injury to the median nerve or its branches are of great importance with regard to postoperative results. Careful imaging studies of the carpal tunnel should be carried out especially in patients with unilateral involvement, presenting with an atypical age or occupation.
12429538 Rhythmic variations in pain, stiffness, and manual dexterity in hand osteoarthritis. 2002 Dec OBJECTIVE: To explore circadian variation in pain, stiffness, and manual dexterity in patients with hand osteoarthritis (OA). METHODS: Twenty one patients with hand OA, as defined by ACR criteria (17 women, four men, mean age 62.2 years, range 52-74 years) self rated pain and stiffness on separate 10 cm horizontal visual analogue scales and performed bead intubation coordinometry (BIC) six times each day (on waking up, at bedtime, and every four hours in between) for 10 consecutive days. Each series (using data with the trend removed if there was a significant trend) was analysed for circadian rhythmicity by a cosine vector technique (single cosinor). With individual data expressed as the percentage of the mean, group rhythm characteristics at period 24 hours were summarised for each variable by population mean cosinor analysis. RESULTS: Individual analyses identified significant circadian rhythms at p
12381508 Treatment trials in ankylosing spondylitis: current and future considerations. 2002 Dec Emerging treatment options in ankylosing spondylitis (AS) are giving new hope to patients with this chronic and potentially disabling disease. Clinical development of new treatments requires that rigorous and well controlled trials be conducted to demonstrate safety and efficacy. A number of classification systems have been developed in recent years as a result of enhanced understanding of the pathogenesis of AS. Although new outcome measures have been developed and a consensus has been reached on the use of assessment instruments in clinical trials, there is still need for improvement and implementation. The ASsessments in Ankylosing Spondylitis (ASAS) Working Group has addressed some of these dilemmas by establishing a core set of domains for the evaluation of AS and by selecting specific assessment methods for each domain. They have also published improvement criteria for assessing short term improvement with symptom modifying antirheumatic drugs and are presently in the process of developing response criteria for disease controlling antirheumatic treatment. Various experts are also currently examining discrepancies and inadequacies of classification systems for AS. Imaging studies, magnetic resonance imaging, in particular, may provide better classification criteria in the near future. In addition to consensus on outcome assessment and classification of AS, lessons learnt from clinical trials in rheumatoid arthritis (RA) may serve as a template for AS. Guidance provided by the United States Food and Drug Administration (FDA) for clinical trials in RA may be of particular use. The FDA has defined the claims that sponsors can receive for RA products and the clinical trial data that would be expected to be submitted to support such claims.
12165033 Helicobacter pylori infection in connective tissue disorders is associated with high level 2002 Aug BACKGROUND: To investigate whether the Helicobacter pylori status influences levels of antibodies against mycobacterial heat shock protein (hsp) 65 and human hsp60 in systemic autoimmune diseases and to study the concentration of anti-H. pylori antibodies in autoimmune patients and healthy controls. MATERIALS AND METHODS: Antibodies against human heat-shock protein hsp60, mycobacterial heat-shock protein hsp65 were analyzed by ELISA. Anti-Helicobacter antibodies were determined by enzyme immunoassay. RESULTS: There was a markedly higher prevalence of H. pylori infection in undifferentiated connective tissue disease (82%) (n = 33) and systemic sclerosis (78%) (n = 55) but not in systemic lupus erythematosus (n = 49), polymyositis/dermatomyositis (n = 14), rheumatoid arthritis (n = 21) or primary Raynaud's syndrome (n = 26) compared with controls (59%) (n = 349). In autoimmune diseases H. pylori infection was associated with elevated levels of antihsp65 (p =.008) but not of antihsp60. Anti-hsp65 levels were significantly higher in H. pylori-infected (n = 129) than in uninfected patients (n = 69) (p =.0007). CONCLUSIONS: These findings indicate that in autoimmune diseases the infection with the H. pylori bacterium is associated with increased concentration of antimycobacterial hsp65.
11801661 Matrix metalloproteinase-19 is expressed in myeloid cells in an adhesion-dependent manner 2002 Feb 1 We have previously reported the isolation of the human matrix metalloproteinase (MMP)-19 (also referred to as RASI) from a synovium of a patient suffering from rheumatoid arthritis and its expression at the cell surface of activated PBMC. In this study, we have analyzed the regulation and cell surface expression of human MMP-19 in several human cell lines and blood-derived cells. Among the cell lines analyzed, MMP-19 is largely expressed by lung fibroblasts as well as by myeloid cell lines THP-1 and HL-60. After fractionating PBMC into CD14- and CD14+ populations we found that only the latter one expresses MMP-19. Although the myeloid cell lines as well as CD14+ cells express MMP-19 without stimulation, its production can be up-regulated by phorbol esters (PMA) or by adhesion. The adhesion-dependent expression was down-regulated or even abrogated by blockade of adhesion or interfering with adhesion-controlling signaling using alpha-tocopherol. We have shown that MMP-19 associates with the cell surface of myeloid cells. This cell surface association was not affected by phospholipase C. However, acidic treatment of the THP-1-derived cell membranes abolished the immunoprecipitation of MMP-19 thereof. Moreover, a high salt treatment of THP-1 cells diminished the MMP-19 detection on the cell surface. This implicates a noncovalent attachment of MMP-19 to the cell surface. Because a truncated form of the MMP-19, in which the hemopexin-like domain was deleted (Delta(hp)MMP-19), does not associate with the surface, the hemopexin-like domain appears to be critical for the cell surface attachment of human MMP-19.