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A 66-year-old man developed chronic watery diarrhea and progressive dyspnea over 1-year. Colonic biopsy revealed a thickened subepithelial collagen layer consistent with collagenous colitis; open lung biopsy revealed pulmonary fibrosis. Only one previous report links extraintestinal manifestations to collagenous colitis. Although the patient had been taking sulfasalazine, the case supports the idea that collagenous colitis, like inflammatory bowel disease, is part of a systemic disorder.
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Guanosine (GUO) has been shown to act as a neuroprotective agent against glutamatergic excitotoxicity by increasing glutamate uptake and decreasing its release. In this study, a putative effect of GUO action on glutamate transporters activity modulation was assessed in hippocampal slices subjected to oxygen and glucose deprivation (OGD), an in vitro model of brain ischemia. Slices subjected to OGD showed increased excitatory amino acids release (measured by D-[(3)H]aspartate release) that was prevented in the presence of GUO (100 µM). The glutamate transporter blockers, DL-TBOA (10 µM), DHK (100 µM, selective inhibitor of GLT-1), and sulfasalazine (SAS, 250 µM, Xc(-) system inhibitor) decreased OGD-induced D-aspartate release. Interestingly, DHK or DL-TBOA blocked the decrease in glutamate release induced by GUO, whereas SAS did not modify the GUO effect. GUO protected hippocampal slices from cellular damage by modulation of glutamate transporters, however selective blockade of GLT-1 or Xc- system only did not affect this protective action of GUO. OGD decreased hippocampal glutamine synthetase (GS) activity and GUO recovered GS activity to control levels without altering the kinetic parameters of GS activity, thus suggesting GUO does not directly interact with GS. Additionally, the pharmacological inhibition of GS activity with methionine sulfoximine abolished the effect of GUO in reducing D-aspartate release and cellular damage evoked by OGD. Altogether, results in hippocampal slices subjected to OGD show that GUO counteracts the release of excitatory amino acids, stimulates the activity of GS, and decreases the cellular damage by modulation of glutamate transporters activity.
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The definition of psoriatic arthritis may be at least inadequate. Moreover, diagnostic criteria proposed may be too restrictive. This may have affected the collection of reliable epidemiological data and may also influenced the classification of the disease. In this article all these aspects are discussed with the aim of offering an up-date on this intriguing disease. Therapeutic options are also examined.
1427 patients initially seen between 1985 and 1994 were included in the study. Of these, 1244 (87%) received a second line drug, 71% within 1.5 years after the disease onset. Overall, antimalarials and parenteral gold were the most frequently prescribed. Statistically significant trends were observed for the years under study. From 1985 to 1987, the most frequently prescribed initial second line drug was parenteral gold, between 1988 to 1990, sulfasalazine, and after 1991, antimalarials. Methotrexate was rarely used as a first choice. Marked variability was observed among rheumatologists in the use of initial second line drugs. In general, year of prescription and prescribing rheumatologist were significantly associated with the selection of all second line drugs but methotrexate. In addition, disease duration and residence (urban or rural) were associated with the selection of antimalarials and parenteral gold.
Patients were evaluated at study entry and after each diet period. Evaluations included a review of symptoms, flexible sigmoidoscopy, rectal biopsy, and rectal dialysis to measure prostaglandin E2 and leukotriene B4 levels.
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Chronic recurrent multifocal osteomyelitis is an unusual inflammatory process of unknown origin involving multiple osseous sites, often recurrently. Selective immunoglobulin M (IgM) deficiency is a rare primary immunodeficiency disease, which can be associated with autoimmune diseases such as systemic lupus erythematosus, Hashimoto's disease, or hemolytic anemia. Here we report a case of a chronic recurrent multifocal osteomyelitis coexisting with selective IgM deficiency.
The main aims of therapy for inflammatory bowel disease (Crohn disease) in children and adolescents are (1) the induction and maintenance of remission, (2) the correction of nutrient deficits and (3) the restoration of growth and maturation. These goals are reached with the use of a combination of therapeutic methods, including pharmacologic agents, nutritional and psychological support, and surgical intervention. The commonly used drugs sulfasalazine, corticosteroids and metronidazole have all been shown to be safe and efficacious when given to children. Newer steroid preparations that are rapidly degraded either in the target tissue or elsewhere are being studied. Of these, budesonide currently shows promise as an efficacious drug with few side effects, but its use in children needs further study. Newer 5-amino-salicylate preparations such as Asacol have been shown to be effective in children, but the number of patients studied is small. Immunomodulatory drugs such as azathioprine and 6-mercaptopurine appear to be safe and efficacious for children; cyclosporine has been used infrequently to treat refractory Crohn disease in children. The use of other agents such as methotrexate, tacrolimus, monoclonal antibodies to cytokines, antibiotics and specific dietary products such as fish oils have not been intensively studied in children with Crohn disease. Nutritional therapy remains a mainstay of treatment because it corrects nutritional deficits, replaces losses and stimulates growth.
We retrospectively analysed 36 (11.4%) of 316 patients with refractory-UC who had been treated with SASP. Clinical and endoscopic activities were evaluated with Lichtiger index and Mayo score, respectively. We analysed the induction-remission rate, predictive factors for the efficacy of SASP, and adverse events.
In the COBRA trial, 155 patients with early RA were treated with sulfasalazine (SSZ) monotherapy (SSZ group) or a combination of step-down prednisolone, methotrexate (MTX) and SSZ (COBRA group). The current 11-year follow-up study of the COBRA trial invited all original patients and performed protocollised scrutiny of clinical records, questionnaires, physical examination, laboratory and imaging tests.
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To analyze whether the intestinal mucosa in rheumatoid arthritis (RA) is immunologically abnormal and whether sulfasalazine (SSZ) possesses any local intestinal immunoregulatory effect.
There is a link between gut and spondyloarthropathies, which extends from the acute ReA triggered by enteritis due to gram-negative bacteria to ankylosing spondylitis and peripheral arthritis in association with Crohn's disease and ulcerative colitis. In addition, in studies using ileocolonoscopy, an unexpectedly high proportion of patients with prolonged or chronic seronegative oligoarthritis or sacroiliitis have inflammatory changes in the terminal ileum or colon or both. These changes have either features of acute gut inflammation or infection, but about one quarter of the patients have chronic lesions, probably early Crohn's disease. The conventional treatment of spondyloarthropathies consists of liberal use of NSAIDs, local corticosteroid injections if indicated, and physiotherapy. In patients with acute ReA, the conventional antimicrobial therapy to eradicate the triggering infection is necessary if there is evidence of chlamydial or gonococcal etiology. This therapy does not, however, influence the course of the subsequent arthritis. Patients with chlamydia arthritis probably host living bacteria for prolonged periods, and they seem to benefit from a prolonged antimicrobial therapy with tetracyclines. In the face of frequent gut involvement in patients with prolonged or chronic spondyloarthropathies, the use of sulfasalazine is the logical alternative, as short-term studies on patients with ankylosing spondylitis indicate.
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Sulphaselazine (SAS) is a drug commonly used to treat patients suffering from chronic inflammatory states such as inflammatory bowel diseases. It was shown that besides bacteriostatic, antiinflammatory and immunosuppressive activity of this drug, the risk of neoplastic changes in the colon and rectum was substantially diminished during ulcerative colitis therapy with SAS. In the present study the effects of SAS and its main metabolites--sulphapyridine (SP) and 5-aminosalicylic acid (5-ASA) on colon adenocarcinoma Caco-2 cells viability and proliferation was evaluated. Significant inhibitory impact of SAS was observed already at 1 mM concentration whereas 5-ASA and SP impaired cellular growth when used at 5 mM concentration. 5 mM SAS exerted a strong cytotoxic effect on Caco-2 cells resulting in their necrotic death. The inhibition of cellular proliferation and the cytotoxic effects of SAS and its metabolites (5-ASA and SP) on the colonic carcinoma cells (Caco-2) confirm the suggestions that these compounds at appropriate concentrations may reduce the risk of neoplastic changes frequently initiated by prolonged inflammatory states.
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The occurrence of ileitis and perianal lesions and also the histopathological findings in our case suggest that HPS and Crohn's disease may truly be associated. Given this similarity and the failure of the standard medical therapy of corticosteroids and azathioprine, our patient received infliximab with marked clinical improvement.
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The course of this single case does not support sulfasalazine treatment or radiotherapy in psoriatic onycho-pachydermo-periostitis.
nIFN-beta may be a safe and effective alternative to induce and maintain remissions in patients with steroid refractory active UC. To validate the presented results, its effect has to be investigated in a randomized, placebo-controlled dose-finding trial.
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Hepatosplenic gammadelta T-cell lymphoma (HS-gammadeltaTCL) is an uncommon type of peripheral T-cell lymphoma, which has been associated in some cases with immunosuppression, mainly after solid organ transplants. We describe a case of HSgammadeltaTCL with a leukaemic course in a patient with Crohn's disease who had received azathioprine during the previous 5.5 years. Sinusoidal infiltration by atypical lymphocytes was observed in the liver, spleen and bone marrow and the typical cytogenetic abnormalities (isochromosome 7 and trisomy 8) were found. The patient did not respond to intensive chemotherapy. This case shows the importance of ruling out HSgammadeltaTCL in patients with hepatosplenomegaly, B-symptoms and any immunosuppressive condition.
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The aim of this study was to evaluate the effect of treatment with methotrexate (MTX), by itself or combined with other non-biological disease-modifying antirheumatic drugs (DMARDs) (methotrexate, MTX with prednisolone, MTX with leflunomide, MTX with chloroquine, and MTX with sulfasalazine) on clinimetric outcomes in a retrospective cohort with a 6-month follow-up and under a Treat to Target (T2T) approach. Patients in treatment with conventional DMARDs and classified as moderate disease activity (MDA) and high disease activity (HDA) were included. Changes in disease activity score (DAS28), health assessment questionnaire (HAQ), tender joint count (TJC), and swollen joint count (SJC) are compared using the Wilcoxon nonparametric test for paired data. Hypothesis contrasts were raised in order to look for differences between the different exposure groups and the outcomes defined by means of the Kruskal-Wallis (KW) nonparametric test. Follow-up was documented in 307 patients, including 250 (81.4%) women. At the onset, 243 subjects (79.2%) were classified as MDA and 64 (20.9%) in HDA. A total of 247 subjects (80.4%) presented some degree of improvement, with 156 subjects (51%) entering remission, which is a significant number (p value = 0.047). There were no differences in the level of severity between the treatment groups (p = 0.98). This study, developed in a cohort of patients with RA with moderate or severe disease activity who were treated with MTX by itself or combined with other non-biological DMARDs under T2T strategy, showed a decrease in the severity of disease activity in 80% of patients. The difference between monotherapy (MTX) and the combinations with other non-biological DMARDs could not be established.
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35 patients with classical form of rheumatoid arthritis were treated with Salazopyrin N "Pharmachim" prepared with the basic substance of the firm "AB-Uppsala"--Sweden. Side effects were seen in 9 patients and in 3 of them the treatment had to be discontinued. After a six months course of treatment remission was found in 18 patients (51%), in 8 patients (22.8%) the result was considered "good" with reduction of the inflammatory activity and in the remaining 5 patients there was little or no effect. The results coincide with those of other authors and support the data for the beneficial action of Salazopyrin N as a basic means in the treatment of rheumatoid arthritis. They also prove that the Bulgarian drug Salazopyrin N is of good quality and can be successfully used in the treatment of rheumatoid arthritis.
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Explore the associations between the tongue appearances in Traditional Chinese Medicine (TCM) and effective response (ACR20 response based on American College of Rheumatology) in rheumatoid arthritis (RA) patients treated with Chinese medicine (CM) and western biomedical combination therapy (WM).
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Sulfasalazine has been the most widely prescribed drug for patients with inflammatory bowel disease. Clinical trials have established its usefulness in treating patients with active ulcerative colitis and Crohn colitis and its important role in maintaining remissions in patients with ulcerative colitis. Despite its widespread acceptance, the usefulness of sulfasalazine has been limited by the occurrence of adverse reactions in about 10 to 20% of the patients. Now the aminosalicylates are emerging as a treatment for both ulcerative colitis and Crohn disease. We have critically reviewed the clinical trials assessing the efficacy of 5-ASA molecules. Therapeutic efficacy of 5-ASA appears to be as good as sulfasalazine but causing less adverse effects. In mild to moderate ulcerative colitis relapse, 2g 5-ASA is active while 1 g 5-ASA seems equivalent to 2g sulfasalazine for maintaining remission. 5-ASA enema in the treatment of distal ulcerative colitis is helpful and can replace topical cortisone administration. Administration of 1g 5-ASA enema a day seems to be the best regimen. In case of Crohn's disease, preliminary studies are encouraging but more date are required to define the indications as well as the regimen.
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N-Propargyl-l(R)-aminoindan, rasagiline, an anti-Parkinson drug, was found to increase the protein and mRNA levels of glial cell line-derived neurotrophic factor (GDNF) in human neuroblastoma SH-SY5Y cells, whereas an analogue without a propargyl residue, aminoindan, did not. GDNF is known to protect dopaminergic neurons in animal and cellular models of Parkinson's disease, and the supplement has been tried for the treatment of degenerating dopamine neurons in Parkinsonian patients. In this paper, intracellular mechanism underlying the induction of GDNF was studied. Rasagiline induced phosphorylation of inhibitory subunit (IkappaB) of nuclear factor-kappaB (NF-kappaB), and translocation of active p65 subunit from cytoplasm into nuclei. Activation of NF-kappaB was also quantitatively determined by NF-kappaB p65 transcription assay. Sulfasalazine, an inhibitor of IkappaB kinase, suppressed the activation of NF-kappaB and the increase of GDNF by rasagiline simultaneously, further indicating the involvement of the IkappaB kinase-NF-kappaB pathway. The results on the activation of the transcription factor by rasagiline are discussed in relation to its possible application as a neuroprotective drug to halt declining of neurons in neurodegenerative disorders, such as Parkinson's and Alzheimer's diseases.
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The association between inflammation of the eyes and the intestine is not often recognized by ophthalmologists. We report two patients who developed peripheral corneal ulcers, episcleritis, and scleritis just prior to the onset of Crohn's disease. The severity of the eye disease paralleled that of the intestinal symptoms, and both conditions subsided after treatment with topical steroids, oral prednisone, oral sulfasalazine, and hydrocortisone retention enemas. Inflammatory bowel disease should always be included in the differential diagnosis of scleritis and uveitis, as the patient may be benefited greatly by appropriate, early therapy of this gastrointestinal disorder.
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Desensitization to sulphasalazine was successful in 16 of 21 (76%) arthritic patients who previously had skin rash from sulphasalazine (success rate: 8 of 13, or 62%) or sulphonamide (success rate: 8 out of 8 patients). Desensitization to sulphasalazine is a simple outpatient procedure which allows many subjects who develop a skin rash to sulphonamide or sulphasalazine to start or continue sulphasalazine treatment.
To investigate whether interactions of sulfasalazine (SSZ) with reduced folate carrier (RFC), the dominant cell membrane transporter for natural folates and methotrexate (MTX), may limit the efficacy of combination therapy with MTX and SSZ in patients with rheumatoid arthritis.
The courses of 90 patients with left-sided ulcerative colitis that was unresponsive or intolerant to conventional therapy were retrospectively reviewed. They had been treated with 5-aminosalicylic acid enemas (mesalamine) on a long-term basis. After an initial 12-week course of treatment, 87% of the patients had improved by at least one grade of inflammation (improvement), and 54% of these were asymptomatic with normal colonic mucosa (remission). Overall, there was an 80% remission rate by 34 weeks. Remission rate was not affected by extent of sigmoid or left-sided colon disease before treatment or prior medication use for ulcerative colitis. Treatment with mesalamine enemas allowed patients to decrease or discontinue glucocorticoid treatment. Patients treated for relapse episodes responded as well as they did to the first course of treatment, whether the relapse occurred after discontinuation of mesalamine or during a tapering of the dose. In conclusion, extending mesalamine treatment to at least 34 weeks was beneficial in inducing a complete remission in 80% of patients unresponsive to conventional therapy.
To evaluate the contemporary diagnostic and therapeutic status for Crohn's disease (CD), and analyze its clinical and pathologic manifestation.
In this population-based retrospective cohort study, sulfasalazine at its optimal dose reduced CVD risk in patients with AS. Celecoxib was neutral regarding CVD risk in AS patients.
Rheumatoid arthritis (RA) is a common cause of disability in the western population, with an annual incidence of 0.05% and a prevalence of 1%. Although a small percentage of patients go into natural remission, the untreated disease progresses to cause disability, morbidity and early mortality. Unravelling of the cytokine network in the pathogenesis of RA has led to the development of drugs that target these cytokines and prevent joint damage. Three biological anticytokine agents, etanercept, infliximab and anakinra, are now available for use in RA. More experience will quantify their safety and benefits. The potency of the older disease-modifying antirheumatic drugs (DMARDs), such as methotrexate and sulfasalazine, is also being realised, especially when used early in the disease process and in combination. Leflunomide is a new DMARD with efficacy similar to methotrexate and sulfasalazine. Symptomatic treatment of RA with nonsteroidal anti-inflammatory drugs has also undergone a revolution with the availability of a new class of COX-2-specific inhibitors. These drugs control inflammation and provide pain relief with less GI toxicity. Management of comorbid conditions associated with RA and its treatment (i.e., osteoporosis, cardiovascular and lung disease) has also become a priority for the rheumatologist. It is hoped that more aggressive use of conventional DMARDs and biological agents will result in less disability and a higher proportion of patients achieving remission.
Clinical remission is the ultimate therapeutic goal in rheumatoid arthritis (RA). Although clinical trials have proven this to be a realistic goal, the concept of targeting at remission has not yet been implemented. The objective of this study was to develop, implement, and evaluate a treat-to-target strategy aimed at achieving remission in very early RA in daily clinical practice.