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ID PMID Title PublicationDate abstract
19735633 Routine histopathologic evaluation in hallux valgus surgery. 2009 Aug BACKGROUND: Anecdotal evidence suggests that specimens submitted for histopathologic assessment during hallux valgus surgery most commonly reveal degenerative changes. The purpose of this study was to evaluate the cost effectiveness of routine examination of tissue from hallux valgus procedures. We hypothesized that such examination rarely diagnoses a new condition and does not alter postoperative management. MATERIALS AND METHODS: Specimens from 315 consecutive primary hallux valgus reconstructions performed between November 1995 and August 2002 were retrospectively analyzed. Patient charts were reviewed to determine the number of cases in which new diagnoses were made or treatment altered based upon histopathologic examination. Cost effectiveness was assessed by identifying the reimbursement for professional fees charged for these analyses. The total reimbursement per new diagnosis made and per alteration of treatment were calculated. RESULTS: Degenerative changes were diagnosed in the majority of speciments (97.5%, 307 of 315). Other diagnoses included rheumatoid arthritis (1.3%, four of 315), gouty arthritis (1.0%, three of 315), and pseudogout (0.3%, one of 315). A new diagnosis was made only in the one patient (0.3%, one of 315) with pseudogout. Postoperative management was unchanged in every case. CONCLUSION: Routine submission of specimens obtained during hallux valgus surgery is not cost effective. New diagnoses are very rare and postoperative management did not change.
19190531 An integrated classification of pediatric inflammatory diseases, based on the concepts of 2009 May Historically, pediatric inflammatory diseases were viewed as autoimmune but developments in genetics of monogenic disease have supported our proposal that "inflammation against self" be viewed as an immunologic disease continuum (IDC), with genetic disorders of adaptive and innate immunity at either end. Innate immune-mediated diseases may be associated with significant tissue destruction without evident adaptive immune responses and are designated as autoinflammatory due to distinct immunopathologic features. However, the majority of pediatric inflammatory disorders are situated along this IDC. Innate immunity has been demonstrated in polygenic disorders, particularly Crohn's disease (CD). A genetic overlap exists between CD and some major histocompatibility complex (MHC) class I-associated diseases, including psoriasis; these diseases seem to represent a true intermediate between autoinflammation and autoimmunity. Conversely, classical autoimmune diseases, with autoantibody and MHC class II associations, including celiac disease and rheumatoid arthritis (RA), have adaptive immune genetic associations, including Cytotoxic T-Lymphocyte Antigen-4 (CTLA4) and PTPN22. This proposed classification is clinically relevant, because innate immune-mediated disorders may respond to cytokine antagonism whereas autoimmune-mediated diseases respond better to anti-T and B cell therapies. Furthermore, the etiopathogenesis of poorly defined "autoimmune" diseases, such as juvenile idiopathic arthritis, may be inferred to have substantial innate immune involvement, based on response to IL-1 antagonism.
19765672 Diseases and drugs that increase risk of acute large bowel ischemia. 2010 Jan BACKGROUND & AIMS: Information is limited on risk factors for acute large bowel ischemia (ALBI). We investigated diseases and drugs associated with ALBI. METHODS: We compared patients hospitalized with ALBI and controls through multivariate analysis of prior outpatient/emergency department/inpatient diagnoses and pharmacy dispensing records. RESULTS: There were 379 cases and 1516 controls (median age, 69 y; range, 25-97 y; 74.4% female). Disorders that were diagnosed in more cases than controls, based on univariate analysis (P < .05), included hypertension, diabetes, chronic obstructive pulmonary disease, atrial fibrillation, congestive heart failure, depression, asthma, coronary artery disease, dementia, rheumatoid arthritis, irritable bowel syndrome, dialysis dependency, diarrhea, and constipation. Drugs dispensed to more cases than controls were antihypertensives, opioids, statins, female hormones, potentially constipating drugs, histamine H(2)-antagonists, immunomodulators, digoxin, clopidogrel/ticlopidine, taxanes/vinca alkaloids, and antibiotics. In all cases, ALBI was associated independently with hypertension (adjusted odds ratio [AOR], 3.21, 95% confidence interval [CI]; 2.28-4.53; P < .0001), chronic obstructive pulmonary disease (AOR, 3.13; 95% CI, 2.06-4.75; P < .0001), diarrhea (AOR, 2.36; 95% CI, 1.13-4.89; P = .0218), atrial fibrillation (AOR, 2.21; 95% CI, 1.34-3.64; P = .0019), congestive heart failure (AOR, 1.94; 95% CI, 1.11-3.39; P = .0205), diabetes (AOR, 1.82; 95% CI, 1.31-2.53; P = .0004), antibiotics (AOR, 3.30; 95% CI, 2.19-4.96; P < .0001), opioids (AOR, 1.96; 95% CI, 1.43-2.67; P < .0001), and potentially constipating drugs (AOR, 1.75; 95% CI, 1.25-2.44; P = .0012). Analysis of only women revealed similar associations except for diarrhea plus rheumatoid arthritis (AOR, 3.27; 95% CI, 1.07-9.96; P = .0370), irritable bowel syndrome (AOR, 2.72; 95% CI, 1.04-7.14; P = .0424), and female hormones (AOR, 1.88; 95% CI, 1.30-2.73; P = .0009). CONCLUSIONS: Heterogeneous diseases and drugs increase the risk of ALBI, consistent with multifactorial pathogenesis.
21625299 Hepatitis C-related arthropathy: Diagnostic and treatment considerations. 2010 Sep Hepatitis C-related arthropathy is one of the most common extrahepatic manifestations of hepatitis C virus (HCV) infection. Although symptoms can be disabling, the prognosis typically is benign. Patients who have atypical chronic inflammatory arthritis with an unknown cause should be evaluated for HCV infection. Testing for antibodies against cyclic citrullinated peptide is useful for distinguishing HCV-related arthropathy from rheumatoid arthritis. Early recognition of HCV infection greatly influences the selection of drug therapy. Although no clinical guidelines are available, many liver disease specialists favor using a stepwise approach to treatment. Future research efforts that focus on the pathogenesis of HCV-related arthropathy and novel therapeutic approaches are needed. (J Musculoskel Med. 2010;27:351-354).
20558342 Inhibition of bone resorption by Tanshinone VI isolated from Salvia miltiorrhiza Bunge. 2010 May 10 During the last decade, a more detailed knowledge of molecular mechanisms involved in osteoclastogenesis has driven research efforts in the development and screening of compound libraries of several small molecules that specifically inhibit the pathway involved in the commitment of the osteoclast precursor cells. Natural compounds that suppress osteoclast differentiation may have therapeutic value in treating osteoporosis and other bone erosive diseases such as rheumatoid arthritis or metastasis associated with bone loss. In ongoing investigation into anti-osteoporotic compounds from natural products we have analyzed the effect of Tanshinone VI on osteoclasts differentiation, using a physiologic three-dimensional osteoblast/bone marrow model of cell co-culture. Tanshinone VI is an abietane diterpene extracted from the root of Salvia miltiorrhiza Bunge (Labiatae), a Chinese traditional crude drug, "Tan-Shen". Tashinone has been widely used in clinical practice for the prevention of cardiac diseases, arthritis and other inflammation-related disorders based on its pharmacological actions in multiple tissues. Although Tanshinone VI A has been used as a medicinal agent in the treatment of many diseases, its role in osteoclast-related bone diseases remains unknown. We showed previously that Tanshinone VI greatly inhibits osteoclast differentiation and suppresses bone resorption through disruption of the actin ring; subsequently, we intended to examine the precise inhibitory mechanism of Tanshinone VI on osteoclast differentiating factor. This study shows, for the first time, that Tanshinone VI prevents osteoclast differentiation by inhibiting RANKL expression and NFkB induction.
20415085 [Rehabilitation exercises after single total knee replacement: a report of 38 cases]. 2010 Mar OBJECTIVE: To study the methods and effects of rehabilitation exercises after single total knee replacement (TKR). METHODS: From May 2007 to May 2009, 38 patients with knee joint diseases were treated with artificial total knee replacement, and the postoperative rehabilitation training was conducted. Among the patients, 20 were males and 18 were females, ranging in age from 50 to 82 years, with an average of 65 years. Course of diseases ranged from 4 to 35 years. Thirty patients were traumatic arthritis, 5 patients were osteoarthritis, and 3 patients were rheumatoid arthritis. Clinical symptoms were knee joint pain and dysfunction; some patients had morning stiffness and bone hypertrophy, a few of them accompanied with knee varus or valgus, quadriceps atrophy. X-ray films showed narrow joint space, osteophyte, cystic changes, and subchondral bone sclerosis. RESULTS: All the patients were followed up ranging from 6 to 12 months. According to HSS knee score system, the mean scores were 40.22 +/- 7.39 points before operation, and 87.47 +/- 6.60 points after rehabilitation. The difference was statistically significant (t = 31.56, P < 0.01). CONCLUSION: Rehabilitation training after single total knee replacement is the key to ensure the effects of the operation. The rehabilitation training in our hospital has satisfactory results, and is worth to popularize.
20410258 IL-6: from its discovery to clinical applications. 2010 May In the late 1960s, the essential role of T cells in antibody production was reported. This led to our hypothesis that T-cell-derived soluble factors would have to be involved in the activation of B cells. The factor that induced B cells to produce immunoglobulins was initially named B-cell stimulatory factor-2. In 1986, we successfully cloned the complementary DNA encoding B-cell stimulatory factor-2, now known as IL-6. At the same time, IFN-beta2 and a 26-kDa protein found in fibroblasts were independently cloned and found to be identical to IL-6. Later, a hybridoma/plasmacytoma growth factor and a hepatocyte-stimulating factor were also proven to be the same molecule as IL-6. Now, we know that IL-6 is a pleiotropic cytokine with a wide range of biological activities in immune regulation, hematopoiesis, inflammation and oncogenesis. Since the discovery of IL-6, we have further clarified its activities, the IL-6R system and the IL-6 signal transduction mechanism. On the basis of the findings, a new therapeutic approach to block the actions of IL-6 by use of a humanized anti-IL-6R antibody has been proven to be therapeutically effective for rheumatoid arthritis, systemic juvenile idiopathic arthritis and Castleman's disease. In this review, I discuss the history of IL-6 research as a paradigm of progress from basic science to clinical applications.
20149898 Phosphodiesterase inhibitors in the management of autoimmune disease. 2010 May Phophodiesterases inhibitors (PDEis) act by inhibiting the catabolism of cyclic nucleotides, cAMP and cGMP, which are ubiquitously expressed in cells of the immune system. Increased levels of cAMP and/or cGMP have been reported to decrease the activity of pro-inflammatory TH1 cells, attenuate experimental autoimmune encephalomyelitis and experimental arthritis. PDE5i like Sildenafil improves endothelial dysfunction and vascular remodelling in patients with pulmonary artery hypertension and refractory secondary Raynaud's phenomenon, with a potential to cause disease modification in the former. Studies in animal models of fibrosis suggest that these drugs have anti-fibrotic effect and may be potentially useful in conditions like scleroderma. They also have been shown to have renoprotective effect in animal models. The emerging trends make it necessary to exploit the full therapeutic potential of this class of drugs in various autoimmune diseases like rheumatoid arthritis, scleroderma, profibrotic conditions and PAH.
19916016 Infliximab and anterior optic neuropathy: case report and review of the literature. 2010 Feb BACKGROUND: Anti-tumor necrosis factor alpha (TNF alpha) agents have been increasingly used to treat patients with Crohn's disease, psoriatic arthritis, rheumatoid arthritis, ankylosing spondylitis, and persistent uveitis. We describe a 68-year-old man with Crohn's esophagitis who developed a possible bilateral toxic anterior optic neuropathy during infliximab infusion. METHODS: This is an observational case report, with review of the PubMed literature from 1977 to present. RESULTS: This 68-year-old man with a 2-year history of Crohn's esophagitis developed acute bilateral visual loss during his third infliximab infusion. His clinical features and laboratory tests were characteristic for a bilateral anterior optic neuropathy. Only three cases of possible infliximab-associated anterior optic neuropathy have been reported in the literature to date. CONCLUSION: It is important to consider the possibility of anterior optic neuropathy, in addition to retrobulbar optic neuritis, in patients who experience sudden-onset visual loss while being treated with infliximab.
19817662 Poor psychological health status among patients with inflammatory rheumatic diseases and o 2010 PURPOSE: To examine psychological health status among patients with inflammatory rheumatic diseases (i.e. rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis) and osteoarthritis in multidisciplinary rehabilitation, and to describe changes in psychological distress, illness cognitions, and pain coping from pre- to post-treatment. METHOD: Eighty-nine patients referred to multidisciplinary rehabilitation completed a set of questionnaires to assess pain (AIMS2-SF), physical functioning (AIMS2-SF), psychological distress (IRGL), illness cognitions (ICQ) and pain coping (PCI) at pre- and post-treatment. Changes in physical functioning, pain, and psychological health status were determined. On the basis of the cut-off scores of psychological distress, distressed, and non-distressed patients were compared on physical and psychological outcomes. RESULTS: Psychological distress was found in 64% of the study sample. In addition, high levels of helplessness and worrying, low levels of acceptance, and moderate levels of physical functioning were found. After treatment, positive changes in pain, psychological distress, and illness cognitions were observed. However, 69% (29/42) of the distressed patients at baseline still experienced elevated levels of psychological distress and maladaptive cognitions. CONCLUSIONS: Psychological distress and maladaptive illness cognitions are important characteristics of this study sample, and psychological distress remains high after rehabilitation. More attention should be given to the appropriate assessment and treatment of psychological distress within multidisciplinary rehabilitation.
19393857 New chemical entities and their market penetration in Finland during the years 1996 throug 2009 Mar BACKGROUND: There is little empirical information about the role of new chemical entities (NCEs) and to what extent they are being adopted in modern health care. OBJECTIVE: We aimed to investigate which NCEs were launched in Finland during the years 1996 through 2005 and how they penetrated the market in Finland. METHODS: NCEs were identified from Finnish drug compendiums and verified from marketing authorization and drug wholesale databases. Market penetration was determined by extracting data about outpatient drug costs and consumption in the year 2005 from drug wholesale databases. RESULTS: Of the 294 NCEs introduced in 1996 through 2005, 55% were authorized nationally and 45% by the European Commission. Two hundred two NCEs (69%) had pharmacy sales in 2005. Most NCEs were for cancer (19), infections (18), cardiovascular diseases (17), and pain and arthritis (14). NCEs introduced from 1996 through 2005 comprised 38% of total outpatient prescription drug costs and 19% of the total volume of NCEs used by outpatients in 2005. The corresponding figures for the NCEs introduced in 2001 through 2005 were 11% and 4%. All drugs for dementia and multiple sclerosis, all biological drugs for rheumatoid arthritis, and most drugs for erectile dysfunction and osteoporosis were introduced during the study period. The cost of NCEs also accounted for >50% of costs for drugs to treat hyperlipidemia, peptic ulcer, psychosis, and diabetes mellitus. CONCLUSIONS: The use of NCEs was greater when measured in monetary value than in volume. The overall costs of NCEs introduced from 1996 through 2005 were high in several major drug classes, although their share of overall use was modest when measured in volume. The market penetration of drugs introduced during 2001 through 2005 was still rather low in 2005.
18657999 Hyaline cartilage involvement in patients with gout and calcium pyrophosphate deposition d 2009 Feb OBJECTIVE: The main aim of the present study was to determine the sensitivity, specificity and accuracy of ultrasonography (US) in detecting monosodium urate and calcium pyrophosphate dihydrate crystals deposits at knee cartilage level using clinical definite diagnosis as standard reference. DESIGN: A total of 32 patients with a diagnosis of gout and 48 patients with pyrophosphate arthropathy were included in the study. Fifty-two patients with rheumatoid arthritis (RA), psoriatic arthritis or osteoarthritis (OA) were recruited as disease controls. All diagnoses were made using an international clinical criterion. US examinations were performed by an experienced sonographer, blind to clinical and laboratory data. Hyaline cartilage was assessed to detect two US findings recently indicated as indicative of crystal deposits: hyperechoic enhancement of the superficial margin of the hyaline cartilage and hyperechoic spots within the cartilage layer not generating a posterior acoustic shadow. RESULTS: Hyperechoic enhancement of the chondrosynovial margin was found in at least one knee of 14 out of 32 (43.7%) patients with gout and in a single knee of only one patient affected by pyrophosphate arthropathy (specificity=99%). Intra-cartilaginous hyperechoic spots were detected in at least one knee of 33 out of 48 (68.7%) patients with pyrophosphate arthropathy and in two disease controls one with OA and the second with RA (specificity=97.6%). CONCLUSIONS: The results of the present study indicate that US may play a relevant role in distinguishing cartilage involvement in patients with crystal-related arthropathy. The selected US findings were found to be highly specific.
20096157 Cardiometabolic comorbidities and the approach to patients with psoriasis. 2009 Dec Psoriasis is a chronic inflammatory, immune-mediated skin disease, which may cause significant deterioration in the quality of life. Recent evidence indicates that psoriasis and psoriatic arthritis are frequently associated with cardiometabolic diseases including myocardial infarction, stroke, diabetes, obesity, dyslipidemia and non-alcoholic fatty liver disease. Although the causal relationship between cardiometabolic comorbidities and psoriasis has not yet been completely proven, it appears that obesity is a relevant risk factor for the development of psoriasis and metabolic syndrome. In addition, moderate to severe psoriasis itself is a risk factor for cardiovascular disease and the metabolic syndrome. Some common genetic traits as well as inflammatory mechanisms may underlie the development of psoriasis and cardiometabolic comorbidities. The presence of comorbidities has important implications in the global approach to patients with psoriasis. Traditional systemic anti-psoriatic agents could negatively affect cardiometabolic comorbidities, and may have important interactions with drugs commonly used by psoriasis patients. In contrast, the recent findings that the risk of myocardial infarction is markedly reduced in rheumatoid arthritis patients who respond to anti-TNF-alpha therapy compared with non-responders supports the hypothesis that the anti-inflammatory effect of TNF-alpha blockers might potentially reduce the cardiovascular risk also in psoriasis patients. Finally, patients with moderate to severe psoriasis should be treated promptly and effectively, should also be encouraged to drastically correct their modifiable cardiovascular risk factors, in particular obesity and smoking habit.
21125159 Autoantibodies in patients with psoriatic arthritis on anti-TNFα therapy. 2010 May INTRODUCTION: Anti-TNFα therapy has been effective in the treatment of patients with refractory psoriatic arthritis (PSA). However, the risk of developing autoantibodies commonly found in rheumatic diseases in PSA patients undergoing this therapy is not clear. OBJECTIVE: To evaluate the induction of specific autoantibodies after anti-TNFα therapy in PSA patients. PATIENTS AND METHODS: Serum samples from 23 PSA patients (women: 61%, age: 45.04 ± 12.68 years, polyarticular: 69.6%, disease duration: 13.3 ± 7.7 years, infliximab: 82.60%) obtained immediately before (baseline) and approximately one year after the introduction of anti-TNF therapy (last sample) (385 ± 131.45 days), were analyzed. The analysis included detection of antinuclear antibodies (ANA) and anti-dsDNA antibodies (indirect immunofluorescence on Hep-2 cells and Crithidia luciliae, respectively); anti-RNP and anti-Sm (passive hemagglutination); and anti-Ro/ SS-A and/or anti-La/SS-B, anti-chromatin, anti-histones, anti-citrullinated peptide (CCP), and anti-cardiolipin (ELISA) antibodies. RESULTS: At baseline, ANA was positive in 47.8% of patients, with predominance of homogeneous nuclear pattern (81.8%). All baseline serum samples were negative for rheumatoid factor and antibodies to cardiolipin, RNP, Sm, Ro/SS-A, anti-La/SS-B, anti-histone, and anti-dsDNA antibodies, while two patients were positive for anti-chromatin and one for anti-CCP. All ANA-positive samples at baseline, except for one, remained positive after the introduction of anti-TNF therapy; however, de novo ANA reactivity was observed in four originally negative patients (33.3%). Anti-Ro/SS-A, La/SS-B, cardiolipin, histones, dsDNA, and rheumatoid factor antibodies remained negative in all final serum samples tested, and anti-chromatin positivity was detected in three other patients. CONCLUSION: Our findings have shown that anti-TNF therapy induced ANA positivity in one third of PSA patients. The concomitant use of methotrexate did not interfere with this finding. In addition, all serum samples were systematically negative for specific rheumatic autoantibodies tested after the introduction of the biological treatment.
20536658 Interstitial type granuloma annulare associated with Sjögren's syndrome. 2010 May We describe a case of granuloma annulare (GA) associated with Sjögren's syndrome (SS) in a 69-year-old woman. She complained of erythematous plaques on the left forearm and neck in addition to dry eyes and mouth. The laboratory and clinical findings also fulfilled the criteria for diagnosis of SS. Histopathological examination revealed the features of interstitial type GA. It is not rare that granulomatous diseases are associated with autoimmune diseases. This case indicated that granulomatous diseases and SS are closely related and that GA should be recognized as a cutaneous manifestation associated with autoimmune diseases, including SS.
19650134 The minor salivary gland biopsy as a diagnostic tool for Sjogren syndrome. 2009 Oct OBJECTIVES/HYPOTHESIS: In suspected cases of Sjogren syndrome (SS), patients are often referred for a labial minor salivary gland biopsy. However, studies have shown this test to be unreliable. Pathologic misinterpretation and immunosuppressive medications may affect the results of the biopsy. As a result, it is best to perform this procedure only when necessary. The purpose of the current study was to review clinical signs and symptoms of patients who underwent a lip biopsy to determine which patients benefited most from this procedure. STUDY DESIGN: Retrospective review. METHODS: A retrospective chart review of patients referred to otolaryngology for a lip biopsy for the diagnosis of SS. RESULTS: Joint pain, salivary gland swelling, and abnormal serology (anti-Sjogren syndrome A/anti-Sjogren syndrome B) were more prevalent in the positive lip biopsy group (grade = 3 or 4). Out of the 12 patients who had both sicca symptoms and positive serology, nine (75%) had a grade = 4. Presence of sicca symptoms and positive serology were predictive of a positive biopsy (P = .017). Excluding those patients who were on immunosuppression for more than 6 weeks prior to the biopsy, the correlation became stronger (P = .011). CONCLUSIONS: In this study, clinical presentation of sicca symptoms and positive serology reliably predicted the results of a lip biopsy. The results of this study suggest that patients with clear criterion for SS may not require a lip biopsy, especially those patients on immunosuppression. When physicians suspect SS, a thorough clinical and laboratory examination is necessary to determine if a patient will benefit from a minor salivary gland biopsy.
19252379 [Study of procedure of labial salivary gland biopsy in Sjögren's syndrome]. 2009 Feb Minor salivary gland biopsy is useful for diagnosis of Sjögren's Syndrome, because it has 87.4% of sensitivity, 87.3% of specificity and 87.4% of accuracy. However, SS cannot be diagnosed solely on focus score (FS). Moreover, FS is at most semi-quantitative. We questioned 30 registered facilities of Society of Japan Sjögren's Syndrome about the method and evaluation of minor salivary gland biopsy. As a result, it turned out that there were no standard methods in the procedure of salivary gland biopsy. The small salivary gland can be reached easily with little invasive method, however there are several problems, which include 1. necessity of a standard technique, 2. minimization of the pain and 3. establishment of proper evaluation system. It is thought that the establishment of a standard technique and evaluation method is necessary to minimize the pain and collect the sufficient amount of tissue. Here we report the analysis of the procedure of minor salivary gland biopsy performed in other institutions as well as in our hospital in order to propose a standardized procedure and evaluation system.
19473996 Kinetic analysis of synovial signalling and gene expression in animal models of arthritis. 2010 May BACKGROUND: Animal models of arthritis are frequently used to evaluate novel therapeutic agents. However, their ability to predict responses in humans is variable. OBJECTIVE: To examine the time course of signalling molecule and gene expression in two models of arthritis to assist with selection of the model and timing of drug administration. METHODS: The passive K/BxN serum transfer and collagen-induced arthritis (CIA) models were studied. Activation of MAP kinase and interferon (IFN)-response pathways was evaluated by quantitative PCR and western blot analysis of ankle joints at various time points during the models. RESULTS: The kinetics of gene expression and kinase phosphorylation were strikingly different in passive K/BxN and CIA. All three MAP kinases (ERK, JNK and p38) and upstream kinases were activated within days in passive K/BxN and declined as arthritis severity decreased. Surprisingly, IFN-regulated genes, including IRF7, were not induced in the model. In CIA, activation of ERK and JNK was surprisingly low and p38 phosphorylation mainly peaked late in the disease. IFN-response genes were activated during CIA, with especially prominent peaks at the onset of clinical arthritis. CONCLUSIONS: Timing of treatment and selection of CIA or passive K/BxN might have an important impact on therapeutic response. p38, in particular, increases during the late stages of CIA. ERK and JNK patterns are similar in passive K/BxN and rheumatoid arthritis (RA), while IFN-response genes in CIA and RA are similar. The dichotomy between RA and animal models could help explain the poor correlation between efficacy in RA and preclinical studies.
20818151 [Analysis of epitopes and function of anti-M3 muscarinic acetylcholine receptor antibodies 2010 Sjögren's syndrome (SS) is an autoimmune disease that affects exocrine glands including salivary and lacrimal glands. It is characterized by lymphocytic infiltration into exocrine glands, leading to dry mouth and eyes. A number of auto-antibodies, such as anti-SS-A and SS-B antibodies, are detected in patients with SS. However, no SS-specific pathologic auto-antibodies have yet been found in this condition. M3 muscarinic acetylcholine receptor (M3R) plays a crucial role in the secretion of saliva from salivary glands. It is reported that some patients with SS carried inhibitory auto-antibodies against M3R. To clarify the epitopes and function of anti-M3R antibodies in SS, we examined antibodies to the extracellular domains (N terminal region, the first, second, and third extracellular loop) of M3R by ELISA using synthesized peptide antigens encoding these domains in 42 SS and 42 healthy controls (HC). Titers and positivity of anti-M3R antibodies to every extracellular domain of M3R were significantly higher in SS than in HC. For functional analysis, human salivary gland (HSG) cells were pre-cultured with IgG from anti-M3R antibodies positive SS, negative SS, and HC. HSG cells were stimulated with cevimeline hydrochloride and intracellular calcium concentration ([Ca(2+)](i)) was measured. IgG from anti-M3R antibodies to the second loop positive SS inhibited the increase of [Ca(2+)](i), but IgG from antibodies to the N terminal or the first loop positive SS enhanced it, while IgG from antibodies to the third loop positive SS showed no effect on [Ca(2+)](i) as well as IgG from anti-M3R antibodies negative SS and HC. These findings indicated the presence of several B cell epitopes on M3R in SS and effect of anti-M3R antibodies on the salivary secretion might differ with these epitopes.
19763667 Cyclosporine A-induced neck fibrosis in a patient with adult-onset Still's disease. 2010 Feb Cyclosporine A (CsA) is an immunosuppressive agent used for the prevention of graft rejection during organ and bone marrow transplantation. CsA is also used for the treatment of various inflammatory rheumatic diseases. Although different side effect profiles have been reported, nephrotoxicity, renal vascular damage, hypertension, and gingival hypertrophy are among the most commonly encountered side effects. The development of massive fibrosis in the neck associated with CsA in a 30-year-old male patient with Still's disease is presented herein. Significant regression was observed after the discontinuation of CsA.