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ID PMID Title PublicationDate abstract
12604155 Gastrointestinal effects of NSAIDs and coxibs. 2003 Feb Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most commonly used drugs in the world, but their use is limited because of their propensity to cause gastrointestinal (GI) injury. All patients are at risk of GI injury but certain risk factors increase the likelihood of adverse GI effects. The most important include a history of ulcer or GI complications, increasing age, concomitant anticoagulation, concomitant corticosteroid use, and high-dose NSAIDs or multiple NSAIDs (including an NSAID plus low-dose aspirin). Concurrent illness (e.g., severe rheumatoid arthritis, heart disease) has also been reported to increase the risk of GI events. NSAID-associated GI side effects markedly increase health care costs, with up to 31% of cost of managing arthritis patients accounted for through the management of GI side effects. The COX-2 specific inhibitors (coxibs) were developed with the aim of maintaining anti-inflammatory efficacy but improving gastrointestinal safety in comparison to non-selective NSAIDs. The use of COX-2 specific inhibitors significantly decreases the rate of endoscopic ulcers as compared to traditional NSAIDs. Prospective GI outcomes studies also indicate that these agents decrease clinical GI events as compared to non-selective NSAIDs. The number of patients needed to treat to avert one clinical event in one year is approximately 40-100. The cost-effectiveness of coxibs increases (the cost per GI event averted decreases) in patients with high-risk clinical features because they have higher rates of GI hospitalizations and greater use of expensive prophylactic co-therapy.
12173278 Arthropathy in art and the history of pain management--through the centuries to cyclooxyge 2002 Apr Preserved human remains, artefacts and works of art contain records of the existence and prevalence of arthropathies, even in the absence of medical texts or formal written accounts, although these also exist for some epochs and cultures. Example objects from the Museum of Medical History in Brussels have been used to illustrate the magnitude of the burden of pain throughout the ages and how rheumatic diseases have indiscriminately afflicted people regardless of their positions in life or occupations. These include both osteoarthritis (OA) and rheumatoid arthritis (RA), as well as the seemingly ubiquitous gout and various skeletal deformities. Adequate pain management has been severely hampered, historically, by obstacles to a comprehensive and systematic classification of diseases posed by the social, religious and philosophical mores of the time, which made differential diagnosis almost impossible to achieve. However, despite this shortcoming, serendipitous events meant that precursors of modern medicines, such as willow bark extracts, were in routine use from the earliest recorded times. It has taken several millennia, however, before empirical treatment has given way to pharmacological rationale. The first clinically acceptable synthetic derivative of the active principle in willow, aspirin, became available only at the turn of the nineteenth century, while non-steroidal anti-inflammatory drugs (NSAIDs) did not arrive on the market until some 60 yr later. At the cusp of the twentieth and twenty-first centuries, physicians have a wider choice of analgesics available than ever before, including the cyclooxygenase-2 inhibitors, which represent the first major advance in NSAID development since the synthesis of the latter compounds themselves.
12051637 Evaluation of Th-1 and Th-2 immune responses in the skin lesions of patients with Blau syn 2002 Jun Blau syndrome is an autosomal dominant syndrome characterized by arthritis, uveitis, skin rash, granuloma, and camptodactyly. It has overlapping symptoms with sarcoidosis and rheumatoid arthritis. Our study was directed toward determining the role of cytokines in granuloma formation in Blau syndrome. Antigenic stimulation usually follows two pathways: Th-1, which activates macrophages and cytotoxic T-lymphocytes and produces interleukin (IL)-2, IL-3, interferon gamma, and tumor necrosis factor alpha, and Th-2, which activates the humoral immune system and produces IL-4, IL-5, and IL-10. The development of cytokine profiles may shed some light on our understanding of this illness. Therefore, we studied the relative roles of two opposing lymphocytes, Th-1 and Th-2, by analyzing their relative expression in the skin lesions of patients with Blau syndrome, using the in situ reverse transcription-polymerase chain reaction technique. Our data revealed a significant upregulation of IL-2, an event that appears to play an important role in the formation of granuloma and in the pathogenesis of Blau syndrome. Expression of IL-10, however, was downregulated, and this may have an inhibitory role in the development of the disease. Further studies would be necessary to confirm the presence of other cytokines and to establish the regulatory roles of Th-1 and Th-2 lymphocytes in the pathogenesis of Blau syndrome.
11965595 Splenic rupture as the presenting manifestation of vasculitis. 2002 Apr BACKGROUND: Although underreported, histologic splenic involvement in Wegener's granulomatosis (WG) is not unusual. Splenic rupture in association with WG, however, is rare. Only 2 cases of nontraumatic splenic rupture have been reported as the initial feature of WG. Isolated cases of splenic rupture also have been noted in rheumatoid arthritis, systemic lupus erythematosus, and polyarteritis nodosa. OBJECTIVE: To report the third case of splenic rupture as the presenting feature of WG and review the literature concerning splenic rupture in other rheumatologic diseases to better delineate a mechanism for this rare occurrence. METHODS: Descriptive case report of 1 patient with WG with antecedent splenic rupture and a review of the relevant literature using a MEDLINE search from 1950 to 2001. RESULTS: Our patient presented with symptoms and signs of WG 2 weeks after nontraumatic splenic rupture. Two similar cases have been reported: one showed splenic vasculitis histologically and the other only a neutrophilic infiltration at the site of the splenic tear and subcapsular zone after surgery. Although splenic capsular and pulp hemorrhage alone without signs of vasculitis were noted in our patient, no other cause (ie, hematologic, infectious, neoplastic, or otherwise) for splenic rupture was found. CONCLUSIONS AND RELEVANCE: As in the 2 reported cases, WG may have been responsible for splenic rupture in our patient. Regardless, early evaluation for connective tissue disease in a patient with spontaneous splenic rupture without apparent cause merits consideration, as it may affect patient follow-up and treatment.
12579593 Use of the Trust in Physician Scale in patients with rheumatic disease: psychometric prope 2003 Feb 15 OBJECTIVES: To assess the psychometric properties of the Trust in Physician Scale and to identify variables associated with patients' trust in their rheumatologist. METHODS: Analyses of self reported data from 713 patients with rheumatoid arthritis, osteoarthritis, or fibromyalgia. Study variables included the Trust in Physician Scale, a decision-making question, a medical skepticism measure, and demographic and health-related measures. Internal consistency and construct validity were assessed using correlational analyses and factor analysis. A regression analysis was conducted to identify factors associated with trust in the rheumatologist. RESULTS: Internal consistency of the scale was high (Cronbach's alpha = 0.87). Scale items also loaded on a single factor. Construct validity was supported by inverse correlations between higher trust scores and both skepticism and independent decision making. Decreased trust was associated with older age, minority status, higher education, diagnosis of fibromyalgia or osteoarthritis, and poorer health. CONCLUSION: The Trust in Physician Scale is appropriate for patients with rheumatic disease. Several patient characteristics appear to be associated with lower trust in the rheumatologist.
12223102 Autoantibody profiling for the study and treatment of autoimmune disease. 2002 Proteomics technologies enable profiling of autoantibody responses using biological fluids derived from patients with autoimmune disease. They provide a powerful tool to characterize autoreactive B-cell responses in diseases including rheumatoid arthritis, multiple sclerosis, autoimmune diabetes, and systemic lupus erythematosus. Autoantibody profiling may serve purposes including classification of individual patients and subsets of patients based on their 'autoantibody fingerprint', examination of epitope spreading and antibody isotype usage, discovery and characterization of candidate autoantigens, and tailoring antigen-specific therapy. In the coming decades, proteomics technologies will broaden our understanding of the underlying mechanisms of and will further our ability to diagnose, prognosticate and treat autoimmune disease.
15142472 Impact of medical comorbid disease on antidepressant treatment of major depressive disorde 2004 Jun A major factor in evaluating and treating depression is the presence of comorbid medical problems. In this paper, the authors will first evaluate studies showing that medical illness is a risk factor for depression. The authors will review a series of randomized, controlled studies of antidepressant treatment in subjects with major depressive disorder (MDD) and comorbid medical illnesses (myocardial infarction, stroke, diabetes, cancer, and rheumatoid arthritis). Most of these studies report an advantage for an active antidepressant over placebo in improvement of depressive symptoms. The authors also will review a series of studies in which the outcome of antidepressant treatment is compared between subjects with MDD with and without comorbid medical illness. In these studies, subjects with medical illness tend to have lower improvement of depressive symptoms and higher rates of depressive relapse with antidepressant treatment compared with MDD subjects with no medical comorbidity. In addition, the authors will review hypotheses on the mechanism of the interaction between medical illness and clinical response in MDD. The paper will conclude that medical comorbidity is a predictor of treatment resistance in MDD.
12951580 Anti-TNF-alpha therapies: the next generation. 2003 Sep The functioning of the immune system is finely balanced by the activities of pro-inflammatory and anti-inflammatory mediators or cytokines. Unregulated activities of these mediators can lead to the development of serious inflammatory diseases. In particular, enhanced tumour-necrosis factor-alpha (TNF-alpha) synthesis is associated with the development of rheumatoid arthritis, psoriatic arthritis and inflammatory bowel disease. Inhibiting TNF-alpha activities in these diseases has been remarkably successful. However, the current injectable protein therapies have associated risks and limitations. An oral, small molecule that regulates TNF-alpha biology could either replace the injectables or provide better disease control when used alone or in conjunction with existing therapies. In this review, we discuss briefly the present understanding of TNF-alpha-mediated biology and the current injectable therapies in clinical use, and focus on some of the new therapeutic approaches with oral, small-molecule inhibitors.
12406431 Therapy for ankylosing spondylitis: new treatment modalities. 2002 Sep The therapeutic options for patients suffering from the more severe forms of spondyloarthritis (SpA) have been rather limited in recent decades. There is now accumulating evidence that anti-tumour necrosis factor (anti-TNF) therapy is highly effective in SpA, especially in ankylosing spondylitis (AS) and psoriatic arthritis (PsA). Based on the data recently published on more than 200 AS patients, and more than 100 PsA patients, this treatment seems to be even more effective than it is in rheumatoid arthritis (RA). The two major anti-TNF-alpha agents currently available, infliximab (Remicade) and etanercept (Enbrel), are approved for the treatment of RA in Europe and in the USA. The situation in SpA is different from RA because there is an unmet medical need, especially in AS, because disease-modifying anti-rheumatic therapy is not available for severely affected patients. Thus, TNF blockers might even be considered first-line immunosuppressive treatment in patients with active AS who are not sufficiently treated with non-steroidal anti-inflammatory drugs (NSAIDs). For infliximab, a dose of 5mg/kg was required, and intervals between 6 and 12 weeks were necessary for constant suppression of disease activity - a major aim also for long-term treatment. However, it remains to be shown whether patients benefit from long-term therapy and whether radiological progression and ankylosis can be stopped. The optimal doses of infliximab might well be determined individually. Allergic reactions and increased susceptibility to tuberculosis are rare side-effects which need to be recognized early. As it stands now, the benefits of anti-TNF therapy in AS seem to outweigh these shortcomings. The efficacy of etanercept was first demonstrated in PsA. A double-blind study has now been performed in AS - with similar results. There is preliminary evidence that both agents also work in other SpA such as undifferentiated SpA. Hopefully, both agents will be approved soon for the short-term treatment of severe SpA. In parallel, studies should be performed to document the long-term efficacy and safety of this treatment.
14528525 Prevalence of the rheumatic diseases in urban Vietnam: a WHO-ILAR COPCORD study. 2003 Oct OBJECTIVE: To determine the prevalence rates of musculoskeletal disorders in an urban Vietnamese population. METHODS: The Community Oriented Program for Control of Rheumatic Disease (COPCORD) Stage I study was carried out in 16 groups in the Trung Liet Commune, Dong Da District, Hanoi City, Vietnam. Phase 1: the WHO ILAR COPCORD Core Questionnaire was applied by primary health care workers to 2119 urban subjects aged 16 years and over. Phase 2: 276 positive responders who had musculoskeletal complaints were interviewed by nurses and examined one week later. Phase 3: 261 positive responders in phase II were examined by 3 rheumatologists and 38% of these subjects required radiographic and blood tests to classify rheumatic disease categories. RESULTS: The response rates were 94.4%, 86.2%, and 94.6% in phases 1, 2, and 3, respectively. The prevalence of musculoskeletal pain was 14.9%. The most common musculoskeletal complaints were knee pain 18.2%, low back pain 11.2%, and soft tissue disorder 15.4%. Functional disability was reported in 6.04% of the survey population. The prevalence of rheumatic diseases was OA 4.1%, rheumatoid arthritis 0.28%, osteoporosis 0.47%, connective tissue disease 0.09%, and gout 0.14%. CONCLUSION: The prevalence of musculoskeletal pain in 2119 adults in an urban population in Vietnam was 14.5%, and osteoarthritis was the most commonly found arthritis.
12701043 Kaposi's sarcoma in rheumatic diseases. 2003 Apr OBJECTIVE: To review the clinical features and outcome of all reported cases of Kaposi's sarcoma in patients with rheumatic diseases. METHODS: In addition to our patient, we identified cases from a Medline search between the years 1966 and 2002. Cases associated with human immunodeficiency virus infection were excluded. RESULTS: Including our patient, there were a total of 25 cases reported (11 men and 14 women). Rheumatoid arthritis was present in 8 cases, polymyositis/dermatomyositis in 5, vasculitis syndromes in 5, systemic lupus erythematosus in 3, polymyalgia rheumatica in 2, and 1 each of undifferentiated connective tissue disease and Behcet disease. All but 1 patient had been given systemic corticosteroids for a duration that ranged from 6 weeks to 22 years, and immunosuppressive drugs from 25 days to 3.5 years. The Kaposi's lesions usually involved the skin on the extremities; internal organ involvement occurred in 7 cases. Most lesions responded to a decreasing dosage of corticosteroids and immunosuppressive drugs, or to the administration of radiation or cytotoxic therapy. Six patients died, 4 of which were related to the progression of Kaposi's sarcoma. CONCLUSION: Kaposi's sarcoma in patients with rheumatologic conditions is rare. The clinical features are similar to those with classical Kaposi's sarcoma. Tumor regression usually occurs with decreasing corticosteroids and/or immunosuppressive drugs, local irradiation, or cytotoxic therapy.
12239955 Mono-arthritis following intensified interferon beta therapy for chronic hepatitis C. 2002 Sep A 39-year-old man with chronic hepatitis C was administered interferon beta (3 MU twice a day) daily. Before interferon therapy, he did not have any symptoms and abnormal data related with autoimmune diseases. On the 16th day of interferon, mono-arthritis occurred at his right elbow. Anti-nuclear antigen or rheumatoid factor was still negative. Discontinuation of interferon for a week with non-steroid anti-inflammatory drug relieved his symptom. Re-administration of interferon (6 MU once a day, three times a week) did not induce arthralgia any more. Administration of interferon beta twice a day may accelerate the cellular immunity twice. Careful observation should be taken even in the cases without pre-existing autoimmune diseases.
12511586 Essential role for proteinase-activated receptor-2 in arthritis. 2003 Jan Using physiological, pharmacological, and gene disruption approaches, we demonstrate that proteinase-activated receptor-2 (PAR-2) plays a pivotal role in mediating chronic inflammation. Using an adjuvant monoarthritis model of chronic inflammation, joint swelling was substantially inhibited in PAR-2-deficient mice, being reduced by more than fourfold compared with wild-type mice, with virtually no histological evidence of joint damage. Mice heterozygous for PAR-2 gene disruption showed an intermediate phenotype. PAR-2 expression, normally limited to endothelial cells in small arterioles, was substantially upregulated 2 weeks after induction of inflammation, both in synovium and in other periarticular tissues. PAR-2 agonists showed potent proinflammatory effects as intra-articular injection of ASKH95, a novel synthetic PAR-2 agonist, induced prolonged joint swelling and synovial hyperemia. Given the absence of the chronic inflammatory response in the PAR-2-deficient mice, our findings demonstrate a key role for PAR-2 in mediating chronic inflammation, thereby identifying a novel and important therapeutic target for the management of chronic inflammatory diseases such as rheumatoid arthritis.
12468820 The use of the Internet as a resource for health information among patients attending a rh 2002 Dec OBJECTIVES: To determine the proportion of patients attending a rheumatology clinic who have access to a computer with Internet capabilities, to establish how often they search for health information, and how difficult or useful they find this resource. METHODS: We performed a questionnaire-based study of consecutive patients attending a rheumatology clinic in two city teaching hospitals over a 1 week period. Patients were asked if they owned or had access to a computer with Internet capabilities, and if they had searched for information on shopping, holidays, entertainment or health information. Further questions were then directed at the nature of the health information, how useful it was and how easy the patient found it to access the details. Patient demographic data were obtained by case record review. RESULTS: One hundred and forty patients were approached; 138 completed questionnaires were collected. One hundred and one respondents (73%) were female. Median patient age was 58 yr (range 18-84). One hundred and seven (78%) had rheumatoid arthritis, with median disease duration of 8 yr (range 6 months to 49 yr). Sixty (43%) had access to the Internet, mostly at home, and used it most frequently for holiday information. Thirty-seven (27% of all respondents) reported that they had searched for medical information on a median of 2 (range 1-10) occasions in the previous 12 months. Of these, 83% perceived the information as useful, 54% discovered something they had not previously known and 31% reported it was easier than asking their doctor or nurse. Patients searched on-line for information on their arthritis (83%), drug treatment (54%), alternative therapies (31%), diet and arthritis (46%) and patient organizations (11%). No patients recalled being advised to search for information by their doctor or nurse. Patients who searched for medical information were younger (median age 48 vs 62 yr; P<0.001), more likely to be employed (32 vs 16%) and more likely to be married or in a stable relationship (84 vs 66%); there were no differences in sex distribution, diagnosis, disease duration or social deprivation. CONCLUSIONS: One in four patients attending our rheumatology clinic had searched the Internet for medical information in the last 12 months. Almost one-third found it easier than asking their health-care professional. Further studies are required to explore the wider application of this resource and to determine the validity and reliability of the information obtained.
15517649 Common aspects of human and primate seronegative arthritis. 2004 Nov A 27-year-old female lowland gorilla developed an asymmetric oligoarthritis 3 months post-partum. There was no evidence of an antecedent gastrointestinal or genitourinary infection. Serum was negative for rheumatoid factor and antinuclear antibody. Synovial fluid revealed 2000 white blood cells with negative cultures and polarized microscopy. Studies on synoviocytes were the following: (1) FACS analysis revealed surface expression of a B27-like epitope of the cells. (2) Analysis of intracellular clearance kinetics of arthritogenic organisms showed peak intracellular colony-forming units at 48 hours after bacterial invasion, and clearance by 13 days post-invasion. (3) Interferon-y (0.1-10.0 ng/ml)accelerated intracellular microbicidal pathways in a dose-dependent fashion. These findings closely parallel those seen in human synoviocytes of patients with spondyloarthropathy. Primate and human seronegative arthritis share clinical and immunologic features, as well as aspects of host:pathogen defense mechanisms. The interplay of genetic and microbial factors underlying this arthritis appears to be conserved across these species boundaries.
14692140 [The cellular immune reaction in synovial fluid lymphocytes to Ureaplasma antigens in pati 2003 Jul INTRODUCTION: Reiter's syndrome (RS) is an seronegative arthritis that occurs after urogenital or enteric infection which in addition with occular and/or mucocutaneous manifestations presents complete form of disease. According to previous understanding arthritis in the RS is the reactive one, which means that it is impossible to isolate its causative agent. However, there are the more and more authors suggesting that arthritis in the urogenital form of disease is caused by the infective agent in the affected joint. This suggestion is based on numerous studies on the presence of Chlamydia trachomatis and Ureaplasma urealyticum in the inflamed joint by using new diagnostic methods in molecular biology published in the recent literature [1-3]. Besides, numerous studies of the humoral and cell-mediated immune response to "triggering" bacteria in the affected joint have supported previous suggestions [4-7]. Aim of the study was to determine whether synovial fluid T-cells specifically recognize the "triggering" bacteria presumably responsible for the Reiter's syndrome. METHOD: The 3H-thymidine uptake procedure for measuring lymphocyte responses was applied to lymphocytes derived concurrently from synovial fluid (SF) and from peripheral blood (PB) [8]. Ureaplasma antigen and mitogen PHA stimulated lymphocytes in 24 RS patients (24 PB samples, 9 SF samples) and the results were compared with those found in 10 patients with rheumatoid arthritis (RA) (10 PB samples, 5 SF samples). Preparation of ureaplasma antigen. Ureaplasma was cultured on cell-free liquid medium [9]. Sample of 8 ml was heat-inactivated for 15 minutes at 601C and permanently stirred with magnetic mixer. The sample was centrifuged at 2000 x g for 40 minutes and than deposits carefully carried to other sterile glass tubes (Corex) and recentrifuged at 9000 x g for 30 minutes. The deposit was washed 3 times in sterile 0.9% NaCl, and final sediment was resuspended in 1.2 ml sterile 0.9% NaCl. BACTERIOLOGY: Chlamydia trachomatis was isolated by cell culture using cycloheximide-treated McCoy cells [10], while Ureaplasma urealyticum was identified according to its biochemical properties grown on cell-free liquid medium [9]. RESULTS: Proliferative response of the PB lymphocytes to stimulation by mitogen and ureaplasma antigen did not differ between RS and RA patients. Also, there was no difference in proliferative response of SF lymphocytes to mitogen stimulation between RS and RA patients (Figure 1). However, proliferation of SF lymphocytes stimulated by ureaplasma antigen was significantly elevated in RS patients compared with the control group. This difference is statistically significant (p < 0.05) (Figure 2). Difference in proliferative response of the PB and SF lymphocytes stimulated by the ureaplasma antigen was not found in RS patients. DISCUSSION: It was found that SF lymphocytes of RS patients showed significantly elevated proliferative response to stimulation by the ureaplasma antigen compared with SF lymphocytes of the control group. There was no difference when the lymphocytes were stimulated by the mitogen. Our findings suggest that elevated proliferative response of lymphocytes is the sign of stimulation cell-mediated immunity to antigen present in inflamed joint. Hence, the main immune response to Ureaplasma is on the cell-mediated level in the affected joint. This confirms the earlier finding reported by Ford et al. who concluded that synovial rather than peripheral blood lymphocytes indicate the microbiological cause of arthritis [11, 12]. Horowitz et al. demonstrated the correlation between clinical remission after antibiotic therapy and eradication of Ureaplasma, together with a decrease in cellular immune response synovial fluid lymphocytes to ureaplasma antigen stimulation [13]. In that study Horowitz did not find statistically significant difference of ureaplasma proliferative response between PB and SF lymphocytes in patients with RS. We obtained the same results. Than we concluded that sensibilization of immune system exist in the presence of foreign antigen in RS patients. The other authors demonstrated higher stimulation indices than the ones we found in our patients [11-15]. This difference may be the result of different preparation of antigens, in other words selection of serotype of Ureaplasma for antigen preparation different conditions of lymphocyte cultivation. We concluded that the presence of antigen, antigen-specific T cells and efficient antigen-presenting cells (CD4+ T cells) in the joint of RS patients strongly suggests that a T-cell-mediated response to bacteria has the central role in the pathogenesis of Reiter's syndrome.
11796406 Therapeutic use of etanercept in polyarticular course juvenile idiopathic arthritis over a 2002 Feb OBJECTIVE: To analyse the treatment response to etanercept in patients with polyarticular course juvenile idiopathic arthritis (JIA). METHODS: 22 patients with polyarticular course JIA (19 females, three males; mean age 13.9 years; mean disease duration 6.3 years; 15 with polyarticular onset, seven with systemic onset, one with residual systemic activity; eight rheumatoid factor positive; eight with erosive disease) were treated with etanercept for up to 24 months. Etanercept was given subcutaneously at 0.4 mg/kg twice a week. Treatment response was ascertained in an open prospective study. RESULTS: All patients showed impressive clinical improvement, with a decrease in swollen joint count by an average of 10.1 joints (mean of 49% decrease), a decrease in tender joint count by 9.3 joints (mean of 94%), and decrease in total joint count by 11.2 joints (mean of 48%). Duration of morning stiffness decreased to less than 10 minutes. Furthermore, haemoglobin concentration increased on average by 14 g/l (mean of 15.3%) and packed cell volume increased by 0.035 (mean increase of 12%), and erythrocyte sedimentation rate decreased on average by 42.8 mm/1st h (mean decrease of 64%). No major side effects were noted. CONCLUSION: Etanercept continues to be clinically effective and well tolerated in patients with polyarticular course JIA over a two year period.
12012021 A new ditriazine inhibitor of NF-kappaB modulates chronic inflammation and angiogenesis. 2002 May We have previously shown that a ditriazine derivative 4,10-dichloropyrido[5,6:4,5]thieno[3,2- d':3,2- d]-1, 2, 3-ditriazine (DTD) modulates acute inflammation in murine models by inhibition of leukocyte functions and expression of inducible enzymes including nitric oxide synthase and cyclooxygenase-2 (COX-2). In the present work, we have demonstrated the anti-inflammatory effect of DTD after oral administration in the rat adjuvant-induced arthritis, by reduction of interleukin-1beta and tumour necrosis factor-alpha levels and COX-2 expression in the inflamed tissues. These mediators were also significantly decreased by DTD treatment in the angiogenesis-dependent murine air pouch granuloma model, where this agent exerted anti-inflammatory and antiangiogenic effects. In vitro experiments indicated that DTD is an inhibitor of the nuclear factor-kappaB (NF-kappaB) pathway of cellular activation in macrophages, in parallel with the regulation of cytokine release. Our results suggest that the anti-inflammatory and antiangiogenic properties of DTD can be related to the inhibition of cytokine and PGE(2) production by interfering with NF-kappaB activation. This compound thus offers a therapeutic potential for the treatment of chronic inflammatory diseases with an angiogenic component, such as rheumatoid arthritis.
12603636 Does chronic daily headache arise de novo in association with regular use of analgesics? 2003 Mar BACKGROUND: The prevalence of chronic daily headache in association with regular use of analgesics is about 2%. Whether regular use of analgesics has a causal or consequential relationship to daily headache has not been established. A causal relationship has been suggested consequent to the observation of improvement or resolution of headache following analgesic withdrawal in patients attending headache clinics, but this observation has not been validated by controlled trials. PURPOSE: The aim of our investigation was to determine whether regular use of analgesics is associated with the development of chronic daily headache de novo and to characterize the clinical phenotype of those headaches by carefully studying chronic daily headache in patients with regular use of analgesics for a nonheadache indication. METHODS: Patients attending a rheumatology-monitoring clinic of second-line agents were interviewed by a training neurologist with regard to their analgesic and headache history. Headache classification was according to the criteria of the International Headache Society. Daily headache characteristics were surveyed via a standardized questionnaire, and headache features were further explored by a trained medical interviewer. RESULTS: Of 110 patients presenting to a rheumatology-monitoring clinic, 73% had a diagnosis of rheumatoid arthritis, 23% had seronegative arthritis, and 4% comprised a miscellaneous group. One hundred three were using one or more analgesics regularly for their arthritis. Of this group, 8 (7.6%) reported a history of chronic daily headache, each of whom reported a history of migraine. The onset of migraine occurred before the onset of chronic daily headache in 7 patients and at about the same time as the chronic daily headache in 1 patient. In those with onset of migraine prior to chronic daily headache, the mean interval before the onset of headache was 30 years (range, 10 to 50 years). Regular use of analgesics preceded the onset of daily headache in 5 patients by a mean of 5.4 years (range, 2 to 10 years). In 1 patient, analgesic use and the development of daily headache occurred at about the same time. In 1 patient, the onset of daily headache preceded regular use of analgesics by almost 30 years. Five of those with regular use of analgesics had been taking an opiate-based preparation in combination with a nonsteroidal anti-inflammatory agent in 4. Two had been on a combination of acetaminophen (paracetamol) and a nonsteroidal anti-inflammatory drug. The minimum number of tablets per week was 7, and the mean was 48 (range, 7 to 87). Of those patients who did not have daily headache, 41% had a history of migraine and 27% reported a history of tension-type headache. CONCLUSION: These findings suggest that individuals with primary headache, specifically migraine, are predisposed to developing chronic daily headache in association with regular use of analgesics.
15041916 [Sjögren's syndrome: clinical and therapeutic features. A review of the literature]. 2004 Jan Sjögren' Syndrome (SS), also named Sicca Syndrome, is a complex disease, characterized by a series of clinical symptoms and signs chiefly represented by xerostomia, xerophthalmia and connectival diseases. The pathogenetic mechanisms consist of an autoimmune process leading to salivary and lacrimal glands progressive destruction. There is a primary form with salivary and lacrimal glands compromission only and a second form in which xerostomia and/or xerophthalmia are associated with connectival diseases like rheumatoid arthritis, systemic lupus erythematosus and scleroderma. The diagnosis of SS is rather difficult and it is based on various world-wide established and accepted criteria: the labial minor salivary glands biopsy and the research of specific seric autoantibodies are the basic elements. From the therapeutic point of view, various types of immunomodulant treatments based on cyclosporine, corticosteroids, methotrexate or alpha-interferon have been proposed with different RESULTS: Cholinergic drugs, like pilocarpine and cevimeline, are also used in order to stimulate the gland functionality.