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ID PMID Title PublicationDate abstract
9807073 Skeletal expansion combined with soft-tissue reduction in the treatment of obstructive sle 1998 Nov Twenty consecutive children, ranging in age from 6 days to 18 years, were treated with skeletal expansion, in addition to soft-tissue reduction, for medically refractory obstructive sleep apnea. The underlying diagnoses were craniofacial microsomia (n = 6), Down syndrome (n = 3), Pierre Robin syndrome (n = 3), cerebral palsy (n = 3), Nager's syndrome (n = 1), Treacher Collins syndrome (n = 1), cri du chat syndrome (n = 1), juvenile rheumatoid arthritis (n = 1), and temporomandibular joint ankylosis (n = 1). Fourteen children had severe medically refractory sleep apnea and were tracheostomy candidates; in the remaining six, tracheostomies were placed shortly after birth and could not be decannulated. Overnight, 12-channel polysomnography was obtained before and after surgery. The mean apnea index improved from 7.42 to 1.26, the mean respiratory disturbance index improved from 25.24 to 1.72, and the mean lowest apnea-related oxygen saturation improved from 68% to 88%. Of the 14 children with medically refractory obstructive sleep apnea, two required tracheostomies. Of the six patients with tracheostomies, five have been decannulated at the time of this writing. Skeletal expansion in conjunction with soft-tissue reduction in the pediatric population permits substantial increases in the volume of both the nasopharynx and oropharynx. Creative use of conventional osteotomies and the application of distraction osteogenesis have enabled surgeons to apply maxillofacial and craniofacial techniques in treating children with obstructive sleep apnea.
9676773 Epidemiology of rheumatic disease in rural Thailand: a WHO-ILAR COPCORD study. Community O 1998 Jul OBJECTIVE: To determine the prevalence rates of musculoskeletal disorders in a rural population of Thailand. METHODS: Nurses applied the WHO-ILAR COPCORD Core Questionnaire to 2463 rural subjects 15 years of age and over. Respondents who had current musculoskeletal pain were examined by 2 rheumatologists within one week after the interview survey. Radiographic and serologic examinations were carried out when required to classify categories of rheumatic disease. RESULTS: Response rates of the interview survey and examination were 99.7 and 94.2%, respectively. Musculoskeletal pain ever by interview was found in 36.2% of respondents. Of these, 22.7, 12.5, 6.5, and 5% had back, knee, hip region, and neck pain, respectively. Four hundred thirty-one cases (17.6%) who had musculoskeletal pain within 7 days of the interview were examined by rheumatologists, who confirmed 12.8, 5.7, 0.08, and 3.4% had back, knee, hip, and neck abnormalities, respectively. Four hundred fifty-eight (18.6%) had past musculoskeletal pain. Total disability rate was 3%, comprising 3.3% in women and 2.6% in men. Treatment rates by self-medication for current and past musculoskeletal pain were 60.3% in women, 65.7% in men. Therapy was by physician 52.1%, paramedics 9.7%, and masseur 6.8%. The rates of disease prevalence were osteoarthritis 11.3%, myofascial pain syndrome 6.3%, low back pain 4.0%, arthralgia 3.2%, gout 0.16%, rheumatoid arthritis and seronegative spondyloarthropathy each 0.12%, and mixed connective tissue disease and unclassified autoimmune disease each 0.04%. CONCLUSION: Back and knee pain caused the greatest burdens of disease, resulting mostly from joint degeneration.
9648990 Increased serum levels of vascular endothelial growth factor in patients with inflammatory 1998 May BACKGROUND: Vascular endothelial growth factor (VEGF) is a potent angiogenic, vascular permeability-enhancing, and calcium-dependent enzyme-modulating cytokine with overexpression in various pathologic disorders, including granulomatous inflammation, tissue repair, delayed hypersensitivity reactions, rheumatoid arthritis, and tissue ischemia. The present study investigates the role of VEGF in chronic inflammatory bowel disease. METHODS: Thirty-one patients with Crohn's disease, 15 patients with ulcerative colitis, and 9 healthy volunteers were studied. VEGF serum levels were measured with a solid-phase enzyme-linked immunosorbent assay. RESULTS: Significantly increased VEGF serum levels were observed in both active Crohn's disease and active ulcerative colitis when compared with healthy controls. Patients with active Crohn's disease and active ulcerative colitis showed significantly higher VEGF serum levels than patients with quiescent disease. No difference was observed between inactive disease and healthy controls. In addition, strongly increased VEGF serum levels were found in patients with Crohn's disease with fistulas in the absence of clinical, endoscopic, histologic, and laboratory findings of disease activity. CONCLUSIONS: Significantly increased VEGF serum levels were observed in patients with active Crohn's disease and ulcerative colitis, which suggests that VEGF has an important role in chronic inflammatory bowel disease. Its possible association with fistulas has yet to be determined.
9538252 Crystal structure of human secretory phospholipase A2-IIA complex with the potent indolizi 1998 Apr Phospholipase A2 is a key enzyme in a number of physiologically important cellular processes including inflammation and transmembrane signaling. Human secretory phospholipase A2-IIA is present at high concentrations in synovial fluid of patients with rheumatoid arthritis and in the plasma of patients with septic shock. Inhibitors of this enzyme have been suggested to be therapeutically useful non-steroidal anti-inflammatory drugs. The crystal structure of human secretory phospholipase A2-IIA bound to a novel potent indolizine inhibitor (120-1032) has been determined. The complex crystallizes in the space group P3121, with cell dimensions of a = b = 75.8 A and c = 51.3 A. The model was refined to an R-factor of 0. 183 for the intensity data collected to a resolution of 2.2 A. It was revealed that the inhibitor is located near the active site and bound to the calcium ion. Although the binding mode of the 120-1032 inhibitor to human secretory phospholipase A2-IIA is similar to that previously determined for an indole inhibitor LY311299, the specific interactions between the enzyme and the inhibitor in the present complex include the oxycarboxylate group which was introduced in this inhibitor. The oxycarboxylate group in 120-1032 is coordinated to the calcium ion and included in the water-mediated hydrogen bonding to the catalytic Asp49. In addition, the ethyl group in 120-1032 gains hydrophobic contacts with the cavity wall of the hydrophobic channel of the enzyme.
9126378 Characterization of monoclonal antibody glycosylation: comparison of expression systems an 1997 Apr 5 CAMPATH-1H is a recombinant humanized murine monoclonal immunoglobulin (IgG1) which recognizes the CDw52 antigen of human lymphocytes, and has been the subject of clinical trials for the treatment of non-Hodgkin's lymphoma and rheumatoid arthritis. Peptide mapping by liquid chromatography-mass spectrometry was used to confirm the predicted amino acid sequences and profile glycosylation for two CAMPATH isotypes expressed in a murine myeloma cell line (NS0) and a single isotype expressed in both Chinese hamster ovary (CHO) and NS0 lines. The three major glycoforms identified in CAMPATH are fucosylated biantennary structures, containing zero, one, or two galactose residues. Glycosylation of the IgG1 form of CAMPATH expressed in CHO cells is consistent with normal human IgG. However, IgG1 and IgG4 expressed in NS0 cells include two potentially immunogenic glycoforms which contain either one or two nonreducing terminal alpha-linked galactose residues. Oligosaccharide structures were characterized by a combination of tandem mass spectrometry, methylation analysis, and exoglycosidase digestion. The strategy used here is designed to be widely applicable to recombinant glycoproteins.
9034996 A systematic review of randomized controlled trials of pharmacological therapy in osteoart 1997 Feb OBJECTIVE: To systematically review all randomized controlled trials (RCT) of pharmacological therapy in osteoarthritis (OA) of the hip. To determine which nonsteroidal antiinflammatory drug (NSAID) is the most effective, and which NSAID is the most toxic. METHODS: A MEDLINE search was used to identify RCT of pharmacological therapy in patients with OA of the hip published between 1966 and August 1994. Qualitative assessments were performed using a quality scoring system designed for NSAID trials in rheumatoid arthritis. Both the design and analysis aspects of the trials were evaluated, each aspect rated on a scale of 0 to 8. A quantitative method, which calculates the ratio of improvement produced by one NSAID to that produced by another, was used to rate the relative efficacy of different NSAID with respect to pain relief. Toxicity comparisons were made according to the authors' findings. RESULTS: 43 RCT were identified, and of these, 39 evaluated NSAID while 4 evaluated only analgesics. The median design and analysis scores were 2 and 4, respectively, 6 NSAID were included in at least 5 trials; of these, indomethacin was rated more effective in 5 of its 7 comparisons, but more toxic in 7 of 12 comparisons. Only 5 of the 29 (17%) NSAID comparisons found statistically significant differences in efficacy. CONCLUSION: NSAID trials in patients with OA of the hip appear to be weakened by the lack of standardization of case definition of OA, and also by the lack of standardization of outcome assessments. No recommendations for the choice of specific NSAID therapy in hip OA can be offered based on this analysis.
9031380 Immunosuppressive drug use during pregnancy. 1997 Feb Women with rheumatic diseases frequently need treatment throughout pregnancy and lactation. Physicians must confront the dual challenge of monitoring the possible effects of the underlying maternal disease and the medications on both mother and child. It is essential that the maternal disease be well controlled before, during, and after pregnancy to ensure the best possible outcome for the mother and child. Corticosteroids have been used extensively and safely in pregnant patients with systemic lupus erythematosus and rheumatoid arthritis; there have been no reports of congenital malformations in the exposed infants. There is considerable experience using azathioprine during pregnancy if the maternal condition requires use of a cytotoxic drug; there has been no increased risk of congenital malformations in the exposed infants. There is limited information on the safety of other medications, including 6-mercaptopurine, cyclophosphamide, and cyclosporine. Methotrexate is contraindicated during pregnancy, and chlorambucil should be avoided because there are other effective immunosuppressive agents available for use. Corticosteroids (prednisone and methylprednisolone) can be used safely during lactation. All other immunosuppressive medications, azathioprine and 6-mercaptopurine, chlorambucil, cyclophosphamide, cyclosporine, and methotrexate, are contraindicated during lactation.
11924836 Anti-cytokine therapies in response to systemic infection. 2001 Dec In the past 5 y, the 28 d mortality in patients with sepsis syndrome has decreased somewhat but still ranges from 30% to 40%; mortality in those patients with septic shock and multiple organ failure is higher. This high mortality is observed despite intensive care units that deliver hemodynamic, metabolic, ventilatory, and renal support. Clearly some patients survive the ordeal but it remains frustrating not being able to stop the downhill course leading to multiple organ failure and death in these patients. New therapies have been sought and tested, including those preventing the biologic activity of two pro-inflammatory cytokines, interleukin-1 (IL-1) and tumor necrosis factor (TNF). Based on animal studies, anti-TNF and IL-1 therapy has been used to "rescue" the patient who continues to deteriorate in the face of considerable support efforts. Unfortunately, these anticytokine therapies have not dramatically reduced 28 d mortality in double-blind, placebo-controlled trials involving nearly 10000 patients, although there is a consistent but statistically nonsignificant decrease in mortality associated with anticytokine therapies. On the other hand, the same anti-TNF and IL-1-based therapies have made a dramatic improvement in the local inflammation and progression of rheumatoid arthritis. It appears that systemic inflammation of sepsis requires more than anticytokine monotherapy to significantly reduce mortality.
11755130 The loss of susceptibility to apoptosis in exudated tissue neutrophils is associated with 2001 Dec 14 Tissue neutrophils, human salivary neutrophils donated from healthy subjects and synovial fluid neutrophils collected from patients with rheumatoid arthritis were compared with circulating blood neutrophils. Concomitant treatment of circulating blood neutrophils with tumor necrosis factor-alpha (TNF-alpha) and cycloheximide induced neutrophil apoptosis, whereas the same treatment failed to induce significant apoptosis in salivary and synovial fluid neutrophils. Caspase-3 activation by TNF-alpha was observed in these tissue neutrophils, although its activity was significantly weaker than that in circulating blood neutrophils. In circulating blood neutrophils, TNF-alpha induced activation of nuclear factor-kappa B (NF-kappa B), whereas, in tissue neutrophils, NF-kappa B had been already activated without any stimulation, and no further activation was induced by the treatment with TNF-alpha. Furthermore, while pretreatment of neutrophils with an NF-kappa B inhibitor produced typical apoptotic changes in circulating blood neutrophils, this inhibitor did not produce any morphological apoptotic changes induced by TNF-alpha in tissue neutrophils. These results indicate that neutrophils undergo marked functional changes such as altered sensitivity to apoptosis-inducing stimuli in association with their exudation from blood into tissue, and that NF-kappa B activation is involved in the acquisition of resistance to TNF-alpha-induced apoptosis.
11387863 [Persistent infiltrative pulmonary disease]. 2001 May 12 Two patients, a woman aged 63 and a man aged 64 years, were admitted with pulmonary complaints and persistent infiltrative lung abnormalities as revealed in chest X-rays. Routine diagnostic analysis did not lead to a diagnosis. However, a pathological examination of biopsies acquired by means of video-assisted thoracoscopic surgery (VATS), revealed bronchiolitis obliterans organising pneumonia (BOOP). In the first patient the BOOP manifested itself as a rapidly progressive disease with fever, pulmonary complaints and X-ray abnormalities. There was no response to standard antibiotic treatment. The other patient had suffered from rheumatoid arthritis for a considerable time and gradually developed BOOP. Both patients recovered following adequate therapy with high doses of oral corticosteroids. BOOP is a pathological-anatomical entity. It is a nonspecific excessive repair response to a variety of stimuli, such as infection, drugs, collagen vascular diseases, inflammatory disorders, transplantation, intoxication and irradiation. BOOP can also occur idiopathically. A high-resolution CT-scan is useful in distinguishing BOOP from interstitial pulmonary fibrosis and other interstitial lung diseases. An open lung biopsy is necessary for the diagnosis BOOP and is best performed by means of VATS. The treatment of BOOP consists of administering high doses of corticosteroids (prednisone 1 mg/kg/day) and if treated adequately, the prognosis is fairly good. Due to the extensive variety in aetiology, the specific diagnostic procedures and the good response to necessary treatment, BOOP should be considered in the differential diagnosis of patients with persistent infiltrative lung disease.
11299025 Transfusion practice in elective orthopaedic surgery. 2001 Apr . The transfusion requirements of 2233 patients who underwent total hip or knee joint arthroplasty procedures at nine Canadian hospitals during 1995-1996 were evaluated. Although 64% of patients were eligible for participation in an autologous blood donation (ABD) programme, only 8% predonated blood. Patients who were eligible for ABD were younger (62 years vs. 70 years) and had fewer medical illnesses (18% vs. 44%) than those who did not predonate. The rate of allogeneic transfusion was 9.0% (95% confidence interval 4.9-13.1%) in patients who predonated as compared with 24.1% (95% confidence interval 22.2-25.9%) in those who did not. Risk factors for the occurrence of an allogeneic transfusion were type of procedure (primary or revision hip arthroplasty), lower baseline haemoglobin, lower body weight, older age and presence of rheumatoid arthritis (P < 0.001). Only patients without risk factors were predicted to have a less than 10% risk of receiving an allogeneic transfusion. Use of preventive strategies was minimal. Two models designed to predict the occurrence of an allogeneic transfusion were evaluated. If allogeneic transfusion rates are to be reduced, eligible patients should be encouraged to participate in ABD programmes. For patients who are ineligible, other preventative strategies should be introduced.
11128025 Characterization of the in vitro and in vivo activity of monoclonal antibodies to human IL 2000 Oct IL-18 is a cytokine with potent IFN-gamma inducing activities as well as an important mediator of Th1 polarized immune responses. In this study we demonstrated that IL-18 induces the concentration-dependent production of the proinflammatory mediators IFN-gamma, IL-6, and GM-CSF, but not the anti-inflammatory cytokine, IL-10 from peripheral blood lymphocytes in the presence of mitogen. Three neutralizing IL-18 monoclonal antibodies (MAbs) were investigated, one of which (2C10) inhibited IL-18 bioactivity with an IC50 of 0.1 nM and had a K(D) of 3.9 x 10(-11) M. A NOD/SCID mouse model engrafted with human peripheral blood lymphocytes was developed to test the in vivo efficacy of this MAb. The IFN-gamma production induced by LPS administration was inhibited approximately 90% by prior dosing of MAb 2C10. The therapeutic utility of a high-affinity IL-18 MAb may be of benefit in Th1-driven autoimmune diseases such as rheumatoid arthritis and Crohn's Disease, where elevated levels of IL-18 have been observed.
11128009 Tibiotalocalcaneal arthrodesis. 2000 Oct The purpose of this multicenter retrospective study of 55 patients (56 ankles) who underwent simultaneous tibiotalocalcaneal arthrodesis with severe disease involving the ankle and subtalar joints was to determine improvement of pain and function. The surgical indications included osteoarthritis, posttraumatic injury, failed previous surgery, talar avascular necrosis, osteoarthritis, and rheumatoid arthritis involving the ankle and subtalar joints. The average age at the time of the operation was 53 years. The average time of follow-up was 26 months after the operation. Fusion was achieved in 48 ankles, with an average time of fusion of 19 weeks. Forty-eight of the 55 patients were satisfied with the procedure. The average leg length discrepancy was 1.4 cm. The average amount of dorsiflexion was 2 degrees and plantar flexion was 5 degrees. Following surgery, 42 patients complained of pain, 40 patients required shoe modification or an orthotic device, and 34 patients had a limp. Fourteen patients described their activity as unlimited. Based on the AOFAS evaluation, the patients scored an average of 66 on the ankle-hind foot scale following surgery. The most common complications were nonunion (8 ankles) and wound infection (6 ankles). This study demonstrates that tibiotalocalcaneal arthrodesis is an effective salvage procedure for patients with disease both involving the ankle and subtalar joints.
11074834 The health impact of chronic recurrent rhinosinusitis in children. 2000 Nov OBJECTIVES: To report and quantify the health-related quality of life of children who require surgical intervention for chronic recurrent rhinosinusitis and to assess the perspective of the child vs that of the parent. DESIGN: Prospective, observational. PATIENTS AND INTERVENTION: Twenty-one of a consecutive sample of 35 children undergoing endoscopic sinus surgery for infectious indications completed, along with their parents, the Child Health Questionnaire. The Child Health Questionnaire measures in parallel both child and parent perceptions of health by means of separate parent proxy report (Child Health Questionnaire-Parent Form 50) and child self-report (Child Health Questionnaire-Child Form 87) questionnaires concerning physical and psychosocial functioning. MAIN OUTCOME MEASURES: Tabulated scores from both the Child Health Questionnaire-Parent Form 50 and Child Health Questionnaire-Child Form 87 were compared with published data from age-matched normative populations and several pediatric chronic disease groups. RESULTS: Significant decrements in the general health of children with chronic recurrent rhinosinusitis compared with a normative sample were observed for both child- and parent-reported data, particularly in the physical domains. Children with rhinosinusitis were perceived by their parents to have significantly more bodily pain (P<.001)and to be more limited in their physical activities (P<.05)than children with asthma, juvenile rheumatoid arthritis, and other chronic disorders. Parent-child perceptions did vary, with parents reporting more pain and general behavioral effects relative to their children's reports in these areas. CONCLUSION: The health impact of chronic recurrent rhinosinusitis as reported by the subjective evaluations of pediatric patients and their parents is severe.
10922951 [Drug-induced oral ulcerations]. 2000 Jun Different side effects of drugs have been described in the oral cavity, including oral ulcerations. Direct contact between drugs and oral mucosa may induce chemical burn or local hypersensitivity. Less frequently, these drug-induced oral ulcerations are part of a complex reaction with cutaneous or systemic manifestations. Sometimes, one or more oral ulcerations appear as the main side-effect of a drug, or exceptionally as solitary lesions. Solitary oral ulcerations usually appear after few weeks of treatment. In most of cases, these lesions resist to conventional treatments, with a rapid healing following the suppression of the responsible drug. This diagnosis is usually difficult, particularly with patients receiving multiple drug therapy. Besides, special attention must be paid to new drugs. Oral ulcerations following symptoms of burning mouth, metallic taste, dysgueusia or agueusia are strongly suggestive of a pharmacological origin. Most of the molecules able to induce solitary oral ulcerations are commonly prescribed in a) rheumatology: NSAI (diclofenac, flurbiprofen, indomethacin, naproxen), long-term rheumatoid arthritis therapy (azathioprine, methotrexate, penicillamine, gold compounds, tiopronin); b) cardiology: angiotensin-converting-enzyme inhibitors (captopril, enalapril), angiotensin 2-receptor antagonist (losartan), anti-angorous (nicorandil), c) psychiatry: antidepressants (fluoxetine, lithium), d) AIDS therapy (foscarnet, zalcitabine).
10873833 The structures of caspases-1, -3, -7 and -8 reveal the basis for substrate and inhibitor s 2000 Jun BACKGROUND: Peptide inhibitors of caspases have helped define the role of these cysteine proteases in biology. Structural and biochemical characterization of the caspase enzymes may contribute to the development of new drugs for the treatment of caspase-mediated inflammation and apoptosis. RESULTS: The crystal structure of the previously unpublished caspase-7 (Csp7; 2.35 A) bound to the reversible tetrapeptide aldehyde inhibitor acetyl-Asp-Glu-Val-Asp-CHO is compared with crystal structures of caspases-1 (2.3 A), -3 (2.2 A), and -8 (2.65 A) bound to the same inhibitor. Csp7 is a close homolog of caspase-3 (Csp3), and these two caspases possess some quarternary structural characteristics that support their unique role among the caspase family. However, although Csp3 and Csp7 are quite similar overall, they were found to have a significantly different substitution pattern of amino acids in and around the S4-binding site. CONCLUSIONS: These structures span all three caspase subgroups, and provide a basis for inferring substrate and inhibitor binding, as well as selectivity for the entire caspase family. This information will influence the design of selective caspase inhibitors to further elucidate the role of caspases in biology and hopefully lead to the design of therapeutic agents to treat caspase-mediated diseases, such as rheumatoid arthritis, certain neurogenerative diseases and stroke.
10714255 Comparison of patellar resurfacing versus nonresurfacing in total knee arthroplasty. 2000 Feb OBJECTIVES: To determine whether resurfacing the patellar component during total knee replacement (TKR) influences the clinical outcome. DESIGN: A retrospective study of data gathered prospectively during the recovery course of patients who underwent TKR with or without patellar resurfacing. SETTING: Victoria General Hospital, Halifax, NS. PATIENTS: One hundred and eighty-five patients operated on between 1992 and 1995. The inclusion criteria were (a) osteoarthritis, (b) replacement carried out by 2 independent surgeons, (c) no comorbid illness such as rheumatoid arthritis, cancer or infection, (d) pre- and postoperative attendance at the assessment clinics. INTERVENTION: TKR with (45) or without (140) patellar replacement. MAIN OUTCOME MEASURES: Range of motion (ROM), pain assessment, Hospital Severity Score (HSS) and complications. RESULTS: There was no statistical difference between the 2 groups with respect to ROM, pain, HSS and complications postoperatively. CONCLUSIONS: Resurfacing the patella during TKR does not seem to influence the clinical outcome with respect to ROM, pain and overall complications. The decision should be based on individual criteria, depending on the preoperative and intraoperative findings. Randomized clinical trials assessing ROM, pain, complications and cost-effectiveness with long-term follow-up are necessary to further investigate this controversial issue.
10516518 Secondary glaucoma in patients with uveitis. 1999 PURPOSE: To evaluate the prevalence of secondary glaucoma (SG), clinical forms of uveitis more frequently associated with glaucoma, and describe the treatment and complications encountered in a cohort of patients with glaucoma and uveitis during a 10-year period. METHODS: The hospital records of patients with uveitis referred to the Immunology Service of the Massachusetts Eye and Ear Infirmary for a decade were reviewed for cases of SG. RESULTS: One hundred and twenty of the 1,254 patients (9.6%) with uveitis developed SG. SG was more frequent in anterior uveitis (67%) but was also associated with posterior uveitis (13%) and pars planitis (4%). Herpetic keratouveitis (22%), Fuchs' iridocyclitis (19%), juvenile rheumatoid arthritis-associated iridocyclitis (16%), syphilis (14%), and sarcoidosis (12%) were the leading types of uveitis associated with SG. Despite aggressive medical and surgical therapy, SG was associated with progressive visual field loss and optic nerve damage in 39 patients (33%). CONCLUSION: SG is an underappreciated, vision-threatening complication in patients with uveitis. Increased vigilance for emergence of this complicating problem during the care of patients with uveitis is warranted, and medical and surgical treatment for reducing IOP should be especially aggressive in these patients. We hypothesize that earlier, more aggressive treatment of uveitis will reduce the presence of glaucoma as an additional vision-robbing complication of uveitis.
10469239 Sulfasalazine prevents T-helper 1 immune response by suppressing interleukin-12 production 1999 Sep Interleukin-12 (IL-12) plays a pivotal role in the development of T-helper 1 (Th1) immune response, which may be involved in the pathogenesis of chronic inflammatory autoimmune disorders. In this study we investigated the effects of sulfasalazine, a drug for treating inflammatory bowel disease and rheumatoid arthritis, on the production of IL-12 from mouse macrophages stimulated with lipopolysaccharide (LPS). Sulfasalazine potently inhibited the production of IL-12 in a dose-dependent manner, in part through the down-regulation of nuclear factor kappaB (NFkappaB) activation in IL-12 p40 gene. Activation of macrophages by LPS resulted in markedly enhanced binding activities to the kappaB site, which significantly decreased upon addition of sulfasalazine as demonstrated by an electrophoretic gel shift assay. Importantly, macrophages pretreated with sulfasalazine either in vitro or in vivo reduced their ability to induce interferon-gamma (IFN-gamma) and increased the ability to induce IL-4 in antigen-primed CD4+ T cells. From these results, sulfasalazine may induce the Th2 cytokine profile in CD4+ T cells by suppressing IL-12 production in macrophages, and sulfasalazine-induced inhibition of IL-12 production in macrophages may explain some of the known biological effects of sulfasalazine.
10410261 Mycobacterium tuberculosis infection in patients with systemic rheumatic diseases. A case- 1999 May OBJECTIVE: To describe the clinical characteristics of patients with systemic rheumatic diseases and tuberculosis. A retrospective case series from 1987 to 1994, drawn from a tertiary-care hospital in Mexico City, was studied. RESULTS: Thirty patients were included (20 women, 10 men), with mean age of 39.8 years (range 14-66), and a mean duration of the systemic rheumatic disease of 44 months (1-372). The rheumatic diseases included systemic lupus erythematosus (SLE) (n = 13), rheumatoid arthritis (7), polymyositis or dermatomyositis (5), and other diseases (5). During the six months previous to the diagnosis of tuberculosis, 22 patients had received corticosteroids, and 13 others immunosuppressants. Mycobacterium tuberculosis was isolated from 18 patients. Pulmonary tuberculosis was found in 10 patients, and extrapulmonary tuberculosis in 20, seven of these with miliary disease. SLE was seen in 6 of the patients with miliary tuberculosis. The clinical manifestations were: fever (67%), weight loss (67%), diaphoresis (60%), cough and sputum (53%), lymph node enlargement (43%), and dyspnea (33%). Sixteen patients had an abnormal chest film. Of 18 patients tested by PPD RT-2, 8 had an induration > 10 mm. Patients were initially treated with 3 or 4 anti-tuberculosis drugs for 15 days to 6 months, followed by 6 to 10 months of isoniazid plus rifampicin. Three relapsed, and 2 died of respiratory failure. CONCLUSIONS: This case series showed a particular pattern of tuberculosis in patients with systemic rheumatic diseases.