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ID PMID Title PublicationDate abstract
15620057 [Is bone infection of endogenous or exogenous origin? A pathophysiological approach]. 2004 Nov Osteomyelitis is a bacterial implant in bone matrix. Infection occurs as a result of a bacteremia, an inoculation during aseptic or orthopedic surgery, or a contiguous infectious focus. Persistent and relapsing infection may be due to three situations: underlying conditions such as diabetes mellitus or rheumatoid arthritis, presence of foreign surgical implant, and a causative bacterial strain. The pathogenesis of osteomyelitis has been explored through various experimental models, involving mostly Staphylococcus (S. aureus, S. epidermidis) and has given new insights. Bacterial adherence to implanted devices or bone matrix via surface proteins is critical for bacterial survival. Further bacterial growth depends on various mechanisms: the capacity to exhibit matrix-embedded lifestyle known as biofilm and the ability for bacterial subpopulations to switch to a dormant metabolic state known as small colony variants. In addition to bacterial factors, the presence of foreign material induces a defect in local inflammatory response partly responsible for the high susceptibility to infection.
15454784 Measuring quality of life in children with adenotonsillar disease with the Child Health Qu 2004 Oct OBJECTIVE: To validate the Child Health Questionnaire (CHQ) and assess the quality of life of inner-city British children with adenotonsillar disease. METHODS: The primary caregiver of a consecutive series of 43 patients referred for adenotonsillar disease to a pediatric otolaryngology clinic completed the Child Health Questionnaire. Questionnaires were analyzed for data quality and completeness, items/scale correlation, internal consistency and discriminant validity, interscale correlation, reliability estimates and external validity. RESULTS: CHQ demonstrated excellent measuring characteristics in our population. In a comparison with healthy children, 11 out of 15 measures of quality of life were significantly depressed in our sample. Compared with children with rheumatoid arthritis, scores were equivalent in most areas, with the exception of the global health subscale and overall physical score, where our sample scored significantly lower. CONCLUSION: The CHQ (PF 28 version) is an accurate and reliable way of assessing the impact of adenotonsillar disease on the quality of life in children in Britain. This appears to be quite significant in most aspects of a child's life.
15228395 Update on the immunology, diagnosis and management of systemic lupus erythematosus. 2004 Jun Lupus occurs with a prevalence of 2-9 in 10,000 people, targeting female and indigenous populations in particular. Lupus and related systemic autoimmune syndromes (scleroderma, Sjögren's syndrome, rheumatoid arthritis and polymyositis) result from a similar set of genetically and environmentally modulated immune disturbances, and the diagnostic and management approach to these conditions is broadly comparable. Evanescent, vague symptoms, restrictive diagnostic criteria and low diagnostic suspicion might have resulted in the under-diagnosis of these problems in the past, imposing considerable burdens on sufferers and the community. Serological screening should be employed cautiously and wisely, given the rapidly occurring changes in methodology, which have lowered their specificity. Close liaison with the immunology laboratories performing these tests is therefore advisable. Clinicians should emphasize the improving prognosis of lupus and related conditions as a result of earlier disease detection, improved educational support systems and refined medical therapies.
15202781 Beyond cholesterol--inflammatory cytokines, the key mediators in atherosclerosis. 2004 May The development of atherosclerotic lesions encompasses a cascade of cellular and molecular responses that can at best be characterized as an inflammatory process, and exhibits striking similarities to autoimmune diseases, such as rheumatoid arthritis. Chemokines, cytokines and their receptors are critically involved in initiation and perpetuation of atherosclerosis, and they play important roles at all levels in the pathogenesis of this disease. In the present article, the currently available information on cytokines and chemokines as key mediators in atherosclerosis is reviewed. Furthermore, based on recent experiences of our own with very early stages of atherosclerosis, possible new ways to make use of these parameters toward improved early detection, prevention and treatment of this disease are indicated.
15191068 Keys to unlocking the mysteries of rheumatic autoimmune disease. 2004 May Autoimmune diseases are thought to affect between 14 million and 22 million people in this country. Despite decades of research, the underlying mechanisms of disease are poorly understood, diagnosis is often difficult, and therapies that minimize systemic side effects are lacking. Major advances in our understanding of human genetic variation and remarkable new technologies are paving the way for dramatically improving our fundamental knowledge of autoimmune diseases. Gene mapping studies have clearly illustrated the complexity of these diseases, which appear to involve many genes. Very high-throughput microarray assays that can measure the expression levels of thousands of genes simultaneously are revealing important insights into key biological pathways that appear to be perturbed in autoimmune diseases. We review recent advances in genetic and genomic studies, focusing primarily on systemic lupus erythematosus and related rheumatic autoimmune diseases such as Sjögren's syndrome and rheumatoid arthritis. Identification of susceptibility genes and dysregulated biological pathways for these diseases is likely to foster development of novel diagnostic and therapeutic approaches that are increasingly tailored to the underlying pathological mechanisms.
15035789 Place of OTC analgesics and NSAIDs in osteoarthritis. 2003 The risk related to the use of non-steroid anti-inflammatory drugs (NSAIDs) depends on the dose and duration of their use, in addition to the nature of the drug, and patient characteristics. The measures of risk and recent promotion of safer drugs have been mostly based on the results of clinical trials using continuous full-dose use of NSAIDs for periods up to 12 months which may not reflect real-life use and risks of the drugs. To assess this we did two studies of the utilisation of NSAIDs, one in a claims database to measure the amount of drugs dispensed to OA patients over 9 months, which showed that only a small fraction of patients actually bought enough analgesics or NSAIDs to cover the whole study period. On average, patients bought enough NSAIDs to cover 60 of 270 days. The second study was a survey of General Practitioners and rheumatologists to assess the number of users of NSAIDs seen over 2 days' consultations, the indications for and patterns of NSAIDs use. 11% of GP patients and 26% of rheumatologists' patients used NSAIDs, one-third for osteoarthritis (OA), about 8-10% for rheumatoid arthritis (RA) and the rest for various painful conditions. In OA and other conditions patients, more than 70% of patients had been taking their NSAIDs for less than 15 days at the time of consultation, whereas 42% of RA patients had been taking them for more than 6 months.
12776765 Evaluating the impact of stress on systemic disease: the MOST protocol in primary care. 2003 May Mental stress has an enormous impact on physical health. This impact commonly manifests as headache, muscle tension, acne, peptic ulcer disease, or a compromised immune system. Stress is also associated with more serious adverse effects, such as cardiovascular disease and exacerbations of rheumatoid arthritis and systemic lupus erythematosus. As these effects are far-reaching, it is important for primary care physicians to identify and manage the symptoms of mental stress in their patients. This is increasingly possible with office-based mental stress testing, which uses cardiovascular markers to identify patients who are overresponders to mental stress, and, thus, at risk for stress-induced disorders. Mental stress in this population can be managed with nonpharmacologic and pharmacologic interventions to improve patients' responses to stress and decrease morbidity and mortality associated with this condition.
12673904 Profile of a pediatric rheumatology practice in Israel. 2003 Jan BACKGROUND: Several studies from Western countries have analyzed the profile of pediatric rheumatology practices. Due to differences in demography and health care systems the profile in Israel may differ from those countries. OBJECTIVE: To describe the profile of a pediatric rheumatology practice in Israel. METHODS: All new patients seen during the course of 2000 as part of my pediatric rheumatology practice in Northern Israel were registered at their initial encounter. Recorded were demographic data, referral patterns, diagnoses, and disease-related data. Diagnoses were grouped together by types of condition. RESULTS: 242 new patients were seen. 39% of the patients had a rheumatic condition, 39% had non-inflammatory conditions, 12% had periodic fever syndromes and for 10% no definitive diagnosis was determined. 14% had chronic rheumatic diseases. The time until diagnosis was significantly greater and more physicians were involved in the evaluation of periodic fever syndromes than in other disease groups. Seventeen (7%) patients had juvenile rheumatoid arthritis (JRA). The minimum estimated incidence of JRA was 8.8 per 100,000 children. CONCLUSIONS: Most patients seen did not have classic inflammatory rheumatic diseases, similar to data from other Western countries. Distinctive to Israel and the Middle East, periodic fever syndromes comprise a large proportion of the pediatric rheumatology practice. These syndromes are relatively difficult for community physicians to diagnose.
12463462 Anti-tumour necrosis factor (TNF)-alpha therapy in undifferentiated spondyloarthropathy. 2002 Nov The cytokine tumour necrosis factor (TNF)-alpha plays a major role in the spinal inflammatory process of spondyloarthropathy. In contrast to rheumatoid arthritis, disease modifying antirheumatic drugs have not been proved effective against inflammation and progressive ankylosis. Initial studies on TNFalpha inhibitors in ankylosing spondylitis are promising and raise the question as to whether early stages of the disease, mostly classified as "undifferentiated spondyloarthropathy" (uSpA), should also be treated with TNFalpha inhibitors. This article summarises the preliminary results of 11 uSpA patients in 4 different trials treated with TNFalpha inhibitors.
12008112 Effect of diet on cancer development: is oxidative DNA damage a biomarker? 2002 May 15 Free radicals and other reactive species are generated in vivo and many of them can cause oxidative damage to DNA. Although there are methodological uncertainties about accurate quantitation of oxidative DNA damage, the levels of such damage that escape immediate repair and persist in DNA appear to be in the range that could contribute significantly to mutation rates in vivo. The observation that diets rich in fruits and vegetables can decrease both oxidative DNA damage and cancer incidence is consistent with this. By contrast, agents increasing oxidative DNA damage usually increase risk of cancer development. Such agents include cigarette smoke, several other carcinogens, and chronic inflammation. Rheumatoid arthritis and diabetes are accompanied by increased oxidative DNA damage but the pattern of increased cancer risk seems unusual. Other uncertainties are the location of oxidative DNA damage within the genome and the variation in rate and level of oxidative damage between different body tissues. In well-nourished human volunteers, fruits and vegetables have been shown to decrease oxidative DNA damage in several studies, but data from short-term human intervention studies suggest that the protective agents are not vitamin C, vitamin E, beta-carotene, or flavonoids.
11988867 Inhibition of vascular endothelial growth factor expression and production by triptolide. 2002 Apr Triptolide, the major component of the diterpenoids of the Chinese herb Tripterygium wilfordii Hook f. (Celastraceae), inhibited vascular endothelial growth factor expression and secretion in endothelial cells treated by 12-O-tetradecanoylphorbol 13-acetate dose-dependently. This effect may be one of the mechanisms underlying the therapeutic effects of triptolide on rheumatoid arthritis.
24383997 Cyclosporin A therapy for interstitial pneumonitis associated with rheumatic disease. 2002 Dec Abstract To determine the efficacy of cyclosporin A (CysA) for the treatment of steroid-resistant interstitial pneumonitis (IP), we enrolled 25 patients with various rheumatic diseases and steroid-resistant IP in a pilot study [4 patients with rheumatoid arthritis (RA), 2 with systemic lupus erythematosus (SLE), 11 with polymyositis/dermatomyositis (PM/DM), 4 with systemic sclerosis (SSc), 1 with mixed connective tissue disease (MCTD), 3 with Sjögren syndrome (SS)]. Twelve patients (48%) showed a persistent response to CysA therapy, and 7 of them had PM/DM, including so-called amyopathic DM. Patients with a persistent response had moderately elevated lactate dehydroxygenase (LDH) levels, whereas patients who died had much higher LDH levels and hypoxia. Even patients with low blood levels of CysA achieved a persistent response. In responding patients, the symptoms, chest X-ray findings, arterial oxygen tension, and LDH level all improved after less than 4 weeks. In conclusion, CysA seem to be useful for treating patients with steroid-resistant IP, whose duration is short and severity is mild.
11932873 Experience with etanercept in an academic medical center: are infection rates increased? 2002 Feb OBJECTIVES: There is little established information regarding the safety of antitumor necrosis factor therapies used outside the setting of clinical trials. This study evaluated the long-term safety and tolerability of open-label use of etanercept when used to treat patients with a variety of systemic rheumatic diseases. Reduction of concomitant corticosteroid and disease-modifying antirheumatic drug was also assessed. METHODS: Retrospective medical record review of 180 patients who were started on etanercept between December 1998 and April 2000 at an academic medical center. RESULTS: Most patients (81%) remained on therapy for longer than 6 months, and a significant number (43%) of patients for longer than 12 months. Etanercept was prescribed for rheumatoid arthritis (RA) in 144 patients and for diseases other than RA, including ankylosing spondylitis, psoriatic arthritis, and polymyositis, in 36 patients. Fifty-six percent of patients taking corticosteroids were able to reduce their dose and 51% of patients were able to taper their methotrexate dosages. Forty-three patients (26%) discontinued etanercept. Reasons for discontinuing therapy included serious adverse events (2.9%), of which infection was most common. These included a psoas abscess secondary to Mycobacterium avium-intracellulare, septic wrist, bacteremia, and septic total hip replacement. Two deaths associated with infection were seen. CONCLUSIONS: The majority of the studied patients tolerated etanercept for longer than 6 months. Many of these patients were able to subsequently taper or even discontinue corticosteroid and methotrexate therapy. Serious infections occurred in this patient population. Our results underscore the value of long-term observation under the conditions of clinical practice beyond controlled clinical trials.
14730616 Genomic absence of the gene encoding T cell receptor Vbeta7.2 is linked to the presence of 2004 Jan OBJECTIVE: It is not yet known whether the absence of certain T cell receptor V(beta) (TCRBV) genes (e.g., due to genomic deletion) has functional significance. We examined this question in relation to a known 21.6-kb insertion/deletion-related polymorphism (IDRP) in the human BV locus. METHODS: New polymerase chain reaction (PCR) genotyping methods were used. Monoclonal antibodies to TCRBV gene products were used to confirm the absence of the relevant proteins. Patients with Sjögren's syndrome (SS) or systemic lupus erythematosus (SLE) were compared with normal controls with regard to TCR genotypes and serologic profiles. RESULTS: There are 3 known haplotypes (I, D1, D2) and 6 possible genotypes related to the 21.6-kb IDRP. Novel PCR-based methods were used to define these genotypes. In subjects with deleted/deleted (D/D) genotypes, T cells could not express V(beta)7.2 TCRs, as assayed with a new antibody specific for V(beta)7.2. This was the sole significant difference between subjects without the insertion and those with either 1 or 2 copies. Surprisingly, we found that the D/D genotype was associated with primary SS, but only when pathogenic autoantibodies were present. CONCLUSION: These results suggest that T cells expressing TCRs with V(beta)7.2 are protective against a pathogenic immune response in SS. Thus, genomic polymorphism of TCR genes (along with the correct HLA alleles) determines whether T cells can direct a pathogenic autoimmune response.
12777459 Salivary gland scintigraphy: the use of semiquantitative analysis for uptake and clearance 2003 Jun OBJECTIVE: Quantitative analysis of (99m)Tc-pertechnetate salivary gland scintigraphy has been used in the evaluation of salivary gland function, but so far no one method can be considered optimal for this task. In this study, a semiquantitative method providing 2 functional parameters for objective assessment of salivary gland function by scintillation camera imaging was tested. METHODS: Twenty-one patients referred for (99m)Tc-pertechnetate thyroid scanning were studied. Two patients with salivary complaints were also included. Dynamic imaging of the anterior head using a scintillation camera was started after a bolus intravenous injection of 185 MBq (5 mCi) (99m)Tc-pertechnetate at 1 frame per 30 s for 30 min. At 15 min after injection, diluted lemon juice was administered orally. Analysis of the dynamic study included time-activity curves of 4 salivary glands (right and left parotid and right and left submandibular). Two parameters of function were defined: uptake rate, taken as the value of the initial slope of the time-activity curve, and washout fraction, which was the relative mobilizable radioactivity from each salivary gland after ingestion of the sialogogue. A parametric image of the washout fraction was also generated. RESULTS: The images showed gradual uptake in the parotid and submandibular glands. Washout was noted immediately after ingestion of the lemon juice. The pattern of the time-activity curve in all glands showed an early fast-rising part followed by a slow-rising component to nearly a plateau within 6-10 min after injection. The mean value of the uptake rate parameter was 0.10 +/- 0.09 cps/s. There was no significant difference between the parotid and submandibular glands or the right and left sides. Uptake in the parotid gland was 1.5-2 times that in the submandibular gland. The washout fraction was 1.40 +/- 1.60 for the parotid glands and 0.77 +/- 0.41 for the submandibular glands (P = 0.005). CONCLUSION: The quantitative analysis method including the uptake rate and the washout fraction parameters would enable objective assessment of salivary function and provide a reproducible means for follow-up of functional impairment in certain diseases.
12737445 Early cancer of the stomach arising after successful treatment of gastric MALT lymphoma in 2003 Mar BACKGROUND: Extranodal marginal zone B-cell lymphoma of the mucosa associated lymphoid tissue (MALT lymphoma) arises in lymphoid tissue acquired through chronic antigenic stimulation as exemplified by Helicobacter pylori. Secondary development of gastric cancer, however, is thought to be a rare event. The detection of a signet ring cell carcinoma during follow-up endoscopy after successful therapy of MALT lymphoma in a patient with Sjögren's syndrome prompted us to analyse the frequency of subsequent gastric cancer in patients with underlying autoimmune disease (AD). METHODS: Patients with early stage MALT lymphoma and an underlying AD were evaluated for the occurrence of a secondary gastric cancer during the course of follow-up. Data analysed included the type of AD, stage of MALT lymphoma, H. pylori status, treatment for MALT lymphoma and response, follow-up, the presence of a secondary cancer, and time to development of cancer. In all patients, histologic samples were reassessed for the extent of gastritis, presence of intestinal metaplasia or focal atrophy at the time of lymphoma diagnosis. RESULTS: A total of eight patients with overt AD at the time of diagnosis of MALT lymphoma were identified. All patients were women aged between 56 and 77 years; 5 had Sjögren's syndrome, 2 had autoimmune thyroiditis (1 along with psoriasis) and 1 suffered from polymyalgia rheumatica. All patients had early stage MALT lymphoma restricted to the mucosa and submucosa at the time of diagnosis, and the presence of H. pylori was found in all cases. Two of these patients achieved complete remission (CR) of the lymphoma following H. pylori eradication, while six were judged unresponsive and underwent chemotherapy, resulting in CR in all cases. One patient died from stroke while being in CR for 2 months following chemotherapy. Two patients (25%) developed early cancer limited to the gastric mucosa while being in CR from lymphoma for 9 and 27 months, respectively, and underwent partial gastrectomy. Final staging of gastric cancer revealed pT1pN0M0 in both cases. Of the remaining 5 cases, 1 patient had a local lymphoma relapse 18 months after CR and was salvaged with radiotherapy. In the remaining 4 patients, no evidence of lymphoma recurrence or a second malignancy has been found so far by regular follow-up every 3 months for a time-span between 52 and 63 months after initial diagnosis. CONCLUSION: Patients with concurrent MALT lymphoma and an underlying autoimmune condition show not only an impaired response to H. pylori eradication but might also be at increased risk for the development of gastric cancer. In view of this, such patients should be followed closely by regular endoscopies after remission of MALT lymphoma.
12226825 Epstein-Barr virus (types 1 and 2) in the tear film in Sjogren's syndrome and HIV infectio 2002 Nov Evidence of Epstein-Barr virus (EBV) shedding in the saliva and tear film has been sought to explain the pathogenesis of the oral and ocular features of Sjogren's syndrome. Patients with human immunodeficiency virus (HIV) infection are purported to have a higher incidence of keratoconjunctivitis sicca. Twenty patients with definite Sjogren's syndrome (primary and secondary), 19 with HIV infection, and 15 normal controls were recruited and studied. Human herpes viruses (EBV 1 and 2, CMV, HZV, and HSV-1) in tear film were detected by polymerase chain reaction of DNA extracted from Schirmer strips. HSV-1, VZV, and CMV were not detected in any tear samples. EBV-1 DNA was found in the tear film of 4 patients with Sjogren's syndrome, which was not significantly different from the control group (P = 0.18). Twelve patients with HIV infection had evidence of EBV-1 in their tears, which was significantly different from controls (P = 0.0002) and patients with Sjogren's syndrome (P = 0.014). EBV-2 was found in 3 patients with HIV and in 1 patient with secondary Sjogren's syndrome, and was always found as a co-infection with EBV-1 (P = 0.01). This represents the first report examining EBV types 1 and 2 in the tear film and also EBV in the tear film of patients with HIV. Shedding of EBV in the tear film was not related to the presence of keratoconjunctivitis sicca in Sjogren's syndrome. EBV-2 co-infection with EBV-1 has not been previously reported in the tear film. EBV infection is abnormally regulated in Sjogren's syndrome and HIV, and it is likely that the presence of EBV in the tear film is related to the patients' altered immune status.
12139947 Role of salivary IgA in the pathogenesis of Sjögren syndrome. 2002 Jul Saliva IgA autoantibodies against M(3) muscarinic acetylcholine receptors (mAChRs) could be a new marker for the diagnosis for Sjögren syndrome (SS) dry mouth. Saliva IgA from dry mouth primary SS (pSS) or secondary SS patients tested by ELISA recognized membrane parotid gland acinar cell antigens and the synthetic 25-mer peptide corresponding to the second extracellular loop of human M(3) mAChRs. Moreover, the IgA fraction was able to inhibit the [(3)H]QNB binding to parotid acinar membrane mAChRs. In addition, the IgA prevented carbachol stimulation of protein secretion by the parotid gland. As controls, IgA and saliva from women without dry mouth and from normal control subjects gave negative results on ELISA, binding, and biological assays, thus demonstrating the specificity of the reaction. IgA autoantibodies against mAChR may be considered among the immunoglobulin factors implicated in the pathophysiology of the development of pSS dry mouth and could be a new marker for differentiating SS dry mouth from non-SS dry mouth.
11878756 Establishment of a convenient system for the long-term culture and study of non-neoplastic 2002 Feb Epithelial cells appear to play an important role in the initiation and maintenance of autoimmune lesions in the salivary glands of patients with Sjogren's syndrome. Therefore, the detailed study of immunological function of salivary gland epithelial cells (SGEC) may provide useful information for the understanding of Sjögren's syndrome pathogenesis. In this report we aimed to formulate a protocol for the establishment of human non-neoplastic SGEC lines as a tool for the study of the physiology and pathophysiology of these cells. Pointing towards a practical approach, we sought to establish SGEC lines from quite a limited amount of biopsy tissue obtained during the diagnostic evaluation of patients. Herein, the favorable conditions for the long-term maintenance of human non-neoplastic SGEC lines are presented and involve the successive application of a serum-containing and a serum-free culture medium, supplemented with essential epithelial growth factors. This protocol has been found reliable and convenient, as attested by the reproducible establishment of non-neoplastic SGEC lines. The analysis of SGEC phenotypic features, as well as a coculture system for the study of interactions between epithelial cells and lymphocytes, are also described. Such techniques may provide valuable means for the functional and molecular investigation of human SGEC and particularly for the study of Sjögren's syndrome and other disorders of glandular epithelia.
15535838 The tandem CCCH zinc finger protein tristetraprolin and its relevance to cytokine mRNA tur 2004 Tristetraprolin (TTP) is the best-studied member of a small family of three proteins in humans that is characterized by a tandem CCCH zinc finger (TZF) domain with highly conserved sequences and spacing. Although initially discovered as a gene that could be induced rapidly and transiently by the stimulation of fibroblasts with growth factors and mitogens, it is now known that TTP can bind to AU-rich elements in mRNA, leading to the removal of the poly(A) tail from that mRNA and increased rates of mRNA turnover. This activity was discovered after TTP-deficient mice were created and found to have a systemic inflammatory syndrome with severe polyarticular arthritis and autoimmunity, as well as medullary and extramedullary myeloid hyperplasia. The syndrome seemed to be due predominantly to excess circulating tumor necrosis factor-alpha (TNF-alpha), resulting from the increased stability of the TNF-alpha mRNA and subsequent higher rates of secretion of the cytokine. The myeloid hyperplasia might be due in part to increased stability of granulocyte-macrophage colony-stimulating factor (GM-CSF). This review highlights briefly the characteristics of the TTP-deficiency syndrome in mice and its possible genetic modifiers, as well as recent data on the characteristics of the TTP-binding site in the TNF-alpha and GM-CSF mRNAs. Recent structural data on the characteristics of the complex between RNA and one of the TTP-related proteins are reviewed, and used to model the TTP-RNA binding complex. We review the current knowledge of TTP sequence variants in humans and discuss the possible contributions of the TTP-related proteins in mouse physiology and in human monocytes. The TTP pathway of TNF-alpha and GM-CSF mRNA degradation is a possible novel target for anti-TNF-alpha therapies for rheumatoid arthritis, and also for other conditions proven to respond to anti-TNF-alpha therapy.