Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
9858423 Ferritin subunits in sera and synovial fluids from patients with rheumatoid arthritis. 1998 Dec OBJECTIVE: To determine the proportion of glycosylated ferritin [ferritin bound to concanavalin A (Con-A)] and ferritin subunits in sera and synovial fluids (SF) from patients with rheumatoid arthritis (RA). METHODS: Ferritin concentrations were measured by a sandwich ELISA using rabbit IgG F(ab')2 anti-human ferritin antibody as a coating antibody. Proportions of glycosylated ferritin were examined using Con-A Sepharose 4B. Ferritin subunits were tested by Western blot analysis. RESULTS: Ferritin concentrations in RA SF were significantly elevated compared to those in osteoarthritis (OA) SF (p < 0.01) and those in RA sera (p < 0.01). Percentages of glycosylated ferritin in SF were low in both RA and OA (RA 11.9 +/- 10.7, n = 41; OA 6.9 +/- 11.0, n = 10). However, percentages of glycosylated ferritin in RA sera (65.9 +/- 15.0, n = 20) were significantly higher than in RA SF (p < 0.01). Western blot analysis revealed both G subunit (23 kDa) and L subunit ( 19 kDa) in RA sera, although SF ferritin was composed mostly of L subunit. CONCLUSION: Significant differences in ferritin molecule composition were observed between sera and SF from patients with RA, which suggests that in RA most SF ferritin is synthesized locally in the affected joint.
9797556 Ceramide, a mediator of interleukin 1, tumour necrosis factor alpha, as well as Fas recept 1998 Aug OBJECTIVES: To examine the effects of ceramide, which is a lipid second messenger of cell surface receptors, including tumour necrosis factor alpha (TNF alpha), interleukin 1 (IL1), and Fas receptors, on rheumatoid arthritis (RA) synovial cells. METHODS: Synovial cells from RA patients and normal skin fibroblasts were cultured with cell permeable ceramide (C2-ceramide). Apoptosis was assessed by microscopic observation of morphological changes, nuclear staining, and DNA electrophoresis. DNA synthesis was examined by thymidine incorporation. RESULTS: C2-ceramide induced reversible morphological changes of synovial cells such as cell rounding within four hours. Subsequently, irreversible nuclear changes characteristic to apoptosis were observed at 48 hours. DNA synthesis was not promoted. The addition of ceramide exerted similar effects on cultured dermal fibroblasts. CONCLUSION: Ceramide induced apoptosis in RA synovial cells. Ceramide could be a second messenger specific for apoptosis of RA synovial cells.
11171679 The national database of the German Collaborative Arthritis Centres: II. Treatment of pati 2001 Mar OBJECTIVE: To describe current treatment of patients with rheumatoid arthritis (RA) in German rheumatology. METHODS: Data from the German rheumatological database of 1998, comprising clinical and patient questionnaire data of 12 992 outpatients with RA seen at 24 collaborative arthritis centres in Germany, were analysed. RESULTS: At the time of documentation, 88% of the patients with RA were undergoing disease modifying antirheumatic drug (DMARD) treatment. Methotrexate (MTX) was prescribed to 56% of the patients (61% with seropositive and 45% with seronegative RA). Combination treatment was used in 15%. MTX was the drug of first choice even in patients with up to one year's disease duration (49%), followed by antimalarial drugs (21%). Patients treated by non-rheumatologists within the previous year had received DMARD treatment in only 33% of the cases. In steroid treatment, low doses (< or = 7.5 mg/day) were used by rheumatologists much more often (44%) than higher doses (12%). 16% of the patients had been inpatients during the previous year, with a median length of stay accumulated over the year of 21 days. Together with stays in inpatient rehabilitation, 22% of all patients had had some form of inpatient treatment. Comprehensive measures such as occupational therapy and patient education were prescribed to fewer than 12% of the patients, mostly during their hospital stay. CONCLUSION: German rheumatologists do follow recent recommendations about early and effective treatment. However, there are still deficits in outpatient care with non-medicinal measures like occupational therapy and patient education, which may partly explain the high hospital admission rates.
9569072 Synovial lining, endothelial and inflammatory mononuclear cell proliferation in synovial m 1998 Feb The extent of synovial cell proliferation in situ and its relationship to the destructive potential of rheumatoid arthritis (RA) is a matter of continuing debate. Notably, the situation has not been elucidated in other inflammatory arthritides [i.e. reactive (ReA) and psoriatic (PsA)], which, although they share some histopathological similarities with RA, develop different patterns of joint involvement. In order to estimate the proliferation of synovial cells in situ in PsA and ReA, and to compare this with RA and with 'non-inflammatory' joint lesions, we have utilized immunostaining of the Ki-67 antigen complemented with Ki-67/CD68 or Ki-67/leucocyte common antigen (LCA, clones 2B11 and PD7/26) double stainings to assess the extent of mononuclear inflammatory cell proliferation. Synovial samples analysed were from 33 patients: RA (n = 8), PsA (n = 13), ReA (n = 6) and six 'non-inflammatory controls' (degenerative or traumatic joint lesions). Thickening of the synovial lining (in particular in RA) and perivascular accumulations of mononuclear inflammatory cells, predominantly lymphocytes, were characteristic features in all synovitides. In contrast to the thickened avascular synovial lining in RA, in 5/13 cases with PsA, blood vessels were observed in the lining. The percentage of lining cells expressing Ki-67 antigen was higher in RA (median = 4.7, interquartile range [Q3-Q1] = 3.9, mean [95% CI] = 3.5 [1.7-5.2], P = 0.0063), PsA (median = 1.2, [Q3-Q1] = 1.9, mean [95% CI] = 1.6 [0.7-2.5], P = 0.007) and ReA (median = 1.4, [Q3-Q1] = 2.3, mean [95% CI] = 1.6 [0.1-3.1], P = 0.0235) than in controls (median = 0.1, [Q3-Q1] = 0.45, mean [95% CI] = 0.2 [0.07-0.5]). In this respect, the differences between different forms of the inflammatory arthritides were not statistically significant (P > 0.05). In RA, PsA and ReA, the percentage of labelled cells in the inflammatory mononuclear cell-rich areas was higher than in controls. The percentage of proliferating endothelial cells was also significantly higher in RA, PsA and ReA than in controls. However, in RA, endothelial expression of Ki-67 antigen was often seen in small blood vessels, whereas in PsA, Ki-67 antigen was preferably expressed in the medium to large blood vessels. Synovial lining cells of the monocyte/macrophage lineage (type A synoviocytes), but not stromal monocytes, demonstrated modest proliferation in situ. These results indicate that although proliferation of synovial lining fibroblasts is a prominent feature in RA, the extents to which this, or in situ proliferation of lymphocytes, contribute to the histopathology of PsA, ReA and RA are comparable. Vascular involvement is suggested by the proliferation of endothelial cells in RA, PsA and ReA in an overlapping manner, but, based on topological differences, such a response may represent diverse pathological features, such as angiogenesis, vascular enlargement and reparative responses to injury.
10812499 High toxicity of sulfasalazine in adult-onset Still's disease. 2000 Mar OBJECTIVE: Sulfasalazine (SSZ) is an anti-rheumatic drug that has been used to treat chronic arthritis. In many reports, the use of SSZ in children with systemic onset juvenile rheumatoid arthritis (JRA) revealed frequent side effects which required discontinuation of the drug. We examined whether there were frequent side effects of SSZ in patients with adult-onset Still's Disease (AOSD). METHODS: From July 1990 to April 1998, we followed 41 AOSD patients. Ten were given SSZ for the treatment of arthritis and the side effects were studied. We also studied 109 consecutive patients with RA who had been given SSZ, as a control group. In addition, we retrospectively studied the side effects and efficacy of SSZ in both groups through their medical records. RESULTS: Six patients (60%, p < 0.01) with AOSD experienced side effects ranging from mild ones like abdominal pain, nausea and vomiting, urticaria, and facial flushing to severe ones such as high fever, hypotension, and severe myelosuppression as well as fulminant hepatitis, which led to the death of one patient. However, 16 patients (14.7%) with RA stopped using SSZ due to mild side effects such as rash, urticaria, gastrointestinal troubles, mild leukopenia, and fever. Three AOSD patients (30%, p = 0.053) and 15 RA patients (13.8%) stopped using SSZ due to its inefficacy. CONCLUSION: We conclude that SSZ appears to have frequent severe side effects in AOSD, as in systemic onset JRA. These potential adverse effects of SSZ should be considered when it is used to treat chronic arthritides with systemic symptoms. Further study of SSZ in the treatment of AOSD in a multi-center, placebo-controlled environment is needed.
10685644 Epstein-Barr virus-associated Hodgkin's lymphoma and legionella pneumophila infection comp 2000 Feb We describe the case of a 53-month-old girl with juvenile rheumatoid arthritis (JRA), complicated by the occurrence of Hodgkin's lymphoma and Legionella pneumophila infection during immunosuppressive treatment with methotrexate (MTX) and cyclosporine A (CSA). The girl had received variable anti-inflammatory combination therapy, including MTX for 28 months and CSA for 3 months. Thirty-six months after the onset of arthritis, the girl presented with an enlargement of the lymph nodes of the mediastinum, the hilum of the lungs, and the abdomen. Concomitantly, a diagnosis of Legionella pneumonia was rendered. Autopsy showed Epstein-Barr virus (EBV)-associated nodular sclerosing Hodgkin's lymphoma. The neoplastic cells were positive for CD15, CD 30, and latent membrane protein 1 (LMP 1). The present case is the second reported to occur in a child, and it lends support to the hypothesis that immunosuppressive treatment may contribute to an increased risk of the development of EBV-associated lymphoproliferative disorders (LPD) in pediatric patients suffering from JRA.
11168012 IL-1 beta- and IL-4-induced down-regulation of autotaxin mRNA and PC-1 in fibroblast-like 2001 Jan Autotaxin (ATX) is a 125-kD ectonucleotide pyrophosphate/phosphodiesterase, which was initially isolated and cloned from human melanoma cells as a potent stimulator of tumour cell motility. ATX shows 44% identity to the plasma cell membrane marker PC-1. Recently, we described the decreased expression of ATX mRNA in cultured fibroblast-like synoviocytes (SFC) of patients with RA by interferon-gamma. In this study using a competitive reverse transcriptase-polymerase chain reaction, we show an increased ATX mRNA expression in SFC from patients with RA in comparison with synoviocytes from non-RA patients. The median ATX mRNA amount in SFC of RA patients (440 pg/microg total RNA) was five-fold higher than the expression in synoviocytes from non-RA patients (80 pg/microg total RNA) or foreskin fibroblasts (MRHF cells, 90 pg/microg total RNA). In contrast to the elevated ATX mRNA expression in SFC of patients with RA, we did not measure increased mRNA amounts of PC-1 in these cells. Both the ATX mRNA amount and the 5'-nucleotide phosphodiesterase (PDE) activity of SFC lysate were reduced after treatment of SFC with the cytokines IL-1beta or IL-4. IL-1beta and IL-4 induced a down-regulation of PC-1 mRNA and protein expression in SFC. In SFC treated with transforming growth factor-beta the expression of PC-1 mRNA and protein was increased, whereas no significant effect on ATX mRNA expression was detectable. Pharmacological drugs used in therapy for RA, such as dexamethasone, cyclosporin, methotrexate and indomethacin, did not show a statistically significant effect on either ATX mRNA or PC-1 mRNA expression. Only pentoxifylline suppressed ATX mRNA as well as PC-1 mRNA expression. In conclusion, we show a tight regulation of ATX and PC-1 gene expression by cytokines detectable in the inflamed tissue of RA. Further investigations will deal with the regulation of ATX protein expression as well as with the function of ATX in RA.
9045920 Clonal analysis of immunoglobulin mRNA in rheumatoid arthritis synovium: characterization 1997 Feb Plasma cells secreting IgG, M, and A abound in the synovium of patients with rheumatoid arthritis, yet their immunoglobulin repertoire and clonal relationship remain to be elucidated. Locally synthesized immunoglobulins probably contribute to the chronic joint inflammatory processes which are characteristic of these patients. To determine whether B lymphocyte proliferation contributes to the synovial plasma cell infiltrate, the clonality of IgG mRNA in individual synovial biopsies from an actively inflamed joint of patients with rheumatoid arthritis was investigated by a combination of cDNA length analysis and DNA sequencing. Particular sizes of immunoglobulin cDNA, detectable in subclasses 1, 3, or 4, were expressed in most synovial biopsies from one patient, suggesting their origin from expanded clones present in each biopsy. To prove a clonal relationship between recurrent cDNA lengths, immunoglobulin cDNA was cloned from three regions of synovium in three patients. The sequence of clones with a recurrent cDNA length was determined. An IgG3 clone found in most synovial biopsies of one patient was encoded by an unmutated copy of the V(H)1 gene, DP7. In contrast, IgG3 clones encoded by mutated versions of the V(H)3 gene DP49 or the V(H)4 gene DP63 were expanded in the other two patients. Different somatic mutants of these clones were isolated from different sites in these patients. The ratio of replacement/silent somatic mutations in these two families of clones suggests that the selective clonal expansion in the synovium of patients with rheumatoid arthritis is due to an antigen-driven immune response.
11669152 Endorphin and enkephalin ameliorate excessive synovial cell functions in patients with rhe 2001 Oct OBJECTIVE: To determine whether endorphin (END) and enkephalin (ENK) modulate excessive synovial cell functions in patients with rheumatoid arthritis (RA). METHODS: Effects of leucine-enkephalin (leu-ENK), methionine-enkephalin (met-ENK), and beta-endorphin (END) on proinflammatory cytokine and matrix metalloproteinase (MMP) production by RA synovial cells were analyzed by immunoblotting, and their mRNA expression by reverse transcription-polymerase chain reaction (RT-PCR) using limiting dilution of complementary DNA. Expression of opioid receptors on RA synovial cells was assessed by immunohistochemical staining, radioreceptor assay, and RT-PCR. RESULTS: Leu-ENK, met-ENK, and END inhibited tumor necrosis factor-alpha and interleukin 1beta production at the level of mRNA expression. ENK and END inhibited MMP-9 production and its enzymatic activity by RA synovial cells. The mu-subtype opioid receptor was expressed in the RA synovial lining and sublining cells. Radioreceptor assay suggested expression of high affinity receptor for END on RA synovial cells. The mu-subtype opioid receptor-specific antagonist, naloxone, reversed the inhibitory effect of the opioid peptides. The opioid peptides inhibited nuclear translocation and phosphorylation of the transcription factor, cyclic AMP responsive element binding protein (CREB) in RA synovial cells. CONCLUSION: Leu-ENK, met-ENK, and END inhibited excessive RA synovial cell functions in vitro. The opioid hormones may have not only antinociceptive action, but also antiinflammatory effects on synovitis itself in RA.
9673632 Changing patterns in the use of slow acting antirheumatic drugs for the treatment of rheum 1998 Jun 12 AIM: To report on the changing use of slow acting antirheumatic drugs in the treatment of rheumatoid arthritis by contrasting prescribing patterns in 1990 and 1995. METHOD: Data were extracted from the case notes of 103 outpatients with rheumatoid arthritis. Results were compared with those obtained in 1990 in a survey of 81 patients using identical methods. RESULTS: There was a significant increase in the use of methotrexate between 1990 and 1995, and a marked decrease in the use of auranofin. A new feature was the use of drugs in combination. Methotrexate was the most effective agent and auranofin least effective (p = 0.02). The agent with the highest average toxicity score was D-penicillamine. The long term tolerability of methotrexate was superior, with a median time for remaining on therapy 6.4 times longer than that of the other slow acting antirheumatic drugs (p = 0.01). CONCLUSIONS: Our results suggest that identified trends in the altered use of slow acting antirheumatic drugs for treatment of rheumatoid arthritis are rationally based on the increased use of the most effective agents and decreased use of those with greater toxicity and lesser efficacy.
10445602 Increased frequency of cystic fibrosis deltaF508 mutation in bronchiectasis associated wit 1999 Jun This study investigated the clinical characteristics and the possible involvement of the cystic fibrosis transmembrane conductance regulator (CFTR) gene in patients with symptomatic diffuse bronchiectasis (DB) associated with rheumatoid arthritis (RA). Twenty-six patients with both RA and DB (group RA+DB) and control groups of 29 consecutive patients with RA but no bronchiectasis (group RA) and 29 patients with symptomatic DB of unknown origin (group DB) were prospectively studied. Among the patients of the RA+DB group, four (15.4%) were heterozygous for the CFTR gene deltaF508 mutation, whereas no deltaF508 mutation was found in patients of the RA and the DB groups (both, p<0.05). This frequency of deltaF508 mutation was also higher than the expected frequency (2.8%) in the general European population (p<0.04). Sweat chloride values and nasal potential differences were normal in three out of four patients carrying the deltaF508 mutation. In the RA+DB group, those with deltaF508 mutation had more frequent chronic sinusitis (p<0.05), a trend toward a more severe pulmonary involvement, and a lower value of nasal potential differences (p<0.01) whereas their rheumatic features had no particularity. In the RA+DB group, patients with adult-onset bronchiectasis (including two with deltaF508 mutation) had a greater reduction in total lung capacity (p<0.05) and lower nasal potential differences (p<0.005) than those with childhood-onset bronchiectasis. This study suggests a possible deleterious effect of the cystic fibrosis transmembrane conductance regulator mutated protein in the airways which may predispose to the development and severity of bronchiectasis in patients suffering from rheumatoid arthritis.
11398914 Rofecoxib: a review of its use in the management of osteoarthritis, acute pain and rheumat 2001 Rofecoxib is a selective cyclo-oxygenase (COX)-2 inhibitor which has little or no effect on the COX-1 isoenzyme at doses up to 1000 mg/day. Rofecoxib has greater selectivity for COX-2 than celecoxib, meloxicam, diclofenac and indomethacin. In well-controlled clinical trials, rofecoxib 12.5 to 500 mg/day has been evaluated for its efficacy in the treatment of osteoarthritis, acute pain and rheumatoid arthritis [lower dosages (5 to 125 mg/day) were generally used in the chronic pain indications]. In the treatment of patients with osteoarthritis, rofecoxib was more effective in providing symptomatic relief than placebo, paracetamol (acetaminophen) and celecoxib and was similar in efficacy to ibuprofen, diclofenac, naproxen and nabumetone. Overall, both the physician's assessment of disease status and the patient's assessment of response to therapy tended to favour rofecoxib. In patients with postsurgical dental pain, pain after spinal fusion or orthopaedic surgery, or primary dysmenorrhoea, rofecoxib provided more rapid and more sustained pain relief and reduced requirements for supplemental morphine use after surgery than placebo. Rofecoxib was more efficacious than celecoxib in patients with acute dental pain and pain after spinal fusion surgery, although celecoxib may have been used at a subtherapeutic dose. In comparison with traditional nonsteroidal anti-inflammatory drugs (NSAIDs) ibuprofen, diclofenac and naproxen sodium, rofecoxib was similar in efficacy in the treatment of acute pain. Although naproxen sodium provided more rapid pain relief than rofecoxib in patients with primary dysmenorrhoea, the reverse was true after orthopaedic surgery: rofecoxib provided more rapid pain relief and less supplemental morphine was needed. Rofecoxib was as effective as naproxen in providing symptomatic relief for over 8700 patients with rheumatoid arthritis. Compared with traditional NSAID therapy, rofecoxib had a significantly lower incidence of endoscopically confirmed gastroduodenal ulceration and, in approximately 13,000 patients with osteoarthritis and rheumatoid arthritis, a lower incidence of gastrointestinal (GI) adverse events. Rofecoxib was generally well tolerated in all indications with an overall tolerability profile similar to traditional NSAIDs. The most common adverse events in rofecoxib recipients were nausea, dizziness and headache. In conclusion, rofecoxib is at least as effective as traditional NSAID therapy in providing pain relief for both chronic and acute pain conditions. Rofecoxib provides an alternative treatment option to traditional NSAID therapy in the management of symptomatic pain relief in patients with osteoarthritis. Initial data from patients with primary dysmenorrhoea and postoperative pain are promising and further trials may confirm its place in the treatment of these indications. Rofecoxib has also shown promising results in patients with rheumatoid arthritis and is likely to become a valuable addition to current drug therapy for this patient population. Importantly, rofecoxib is associated with a lower incidence of GI adverse events than traditional NSAIDs making it a primary treatment option in patients at risk of developing GI complications or patients with chronic conditions requiring long term treatment.
10824284 Symptomatic cervicogenic headache. 2000 Mar Cervicogenic headache is a little-known clinical condition whose true importance has only recently been recognized. A number of causes may lie at the basis of the onset of headache (symptomatic cervicogenic headache). However, despite exhaustive attempts, sometimes it is not possible to identify a clear cause responsible for the onset of the syndrome (primitive cervicogenic headache). The genesis of symptomatic cervicogenic headaches sometimes may be easy to identify as a result of a close, pre-existing, cause-effect relationship (i.e. trauma). On other occasions it may be much more laborious to pinpoint the pathology responsible for headache (some cranio-cervical anomalies, etc.). Clinically, it is necessary to perform a thorough preliminary clinical and anamnestic evaluation which can orient subsequent investigations to achieve a diagnosis in the least time possible with the minimum discomfort to the patient and his relatives, not to mention lower costs for society.
10600505 Inflammatory cytokines induced down-regulation of m-calpain mRNA expression in fibroblasti 1999 Dec 20 Our previous reports revealed that calpain has proteoglycanase activity and exists in synovial fluid in osteoarthritis and rheumatoid arthritis. We examined the effects of cytokines on expression of the calpain-calpastatin system in fibroblastic synoviocytes (FLS). Primary cultures of human FLS from osteoarthritis (OA) and rheumatoid arthritis (RA) patients were stimulated with inflammatory cytokines and the amounts of m-calpain and calpastatin mRNAs expressed were determined by Northern blotting. Northern blots were subjected to computerized densitometer and band intensities were determined. Interleukin-1 (IL-1) down-regulated m-calpain and tissue-type calpastatin mRNA expression in OA and RA FLS. In RA FLS, although IL-6 did not alter m-calpain mRNA expression, IL-1 + tumor necrosis factor (TNF) and IL-1 + transforming growth factor (TGF) down-regulated m-calpain mRNA expression. These results provide new information about the effects of inflammatory cytokines on calpain and calpastatin system in OA and RA pathology.
10025103 [Cooperation between the family physician, rheumatologist, hospital and rehabilitation cli 1998 Dec The building-up of multipurpose arthritis centers in Germany led to a network including outpatient and inpatient services, primary care physicians, rheumatologists, physiotherapists, occupational therapists, psychologists, acute care clinics, and rehabilitation centers. The structural improvement in the care of patients with chronic inflammatory rheumatic diseases has to be followed by an improvement of processes in the care of these patients and by an improvement of outcome. Coordination offices can help not only to further improve cooperation between primary care physicians, specialized rheumatologists and hospitals but also to establish a comprehensive clinical quality management.
10332215 [A case of rheumatoid arthritis with bucillamine-induced myasthenia gravis treated by immu 1999 Feb We report a case of 48-year old female with rheumatoid arthritis (RA) complicated with myasthenia gravis. In 1988, she was diagnosed of having RA, and several therapeutic drugs were administered, but her disease activity was in poor control. In July 1993, bucillamine (BU) was started at a dose of 100 mg/day, and her arthritis subsided. However, in October 1996, she was admitted with a rapidly progressive ptosis and double vision in the left eye, which became prominent in the evening. Because serum concentration of the antibody to acetylcholine receptors (AchR Ab) was elevated at 12.6 nmol/l, and the ptosis was reversed immediately after a tensilon test, ocular type myasthenia gravis (MG) was diagnosed and it was thought to have been induced by BU. Immunoadsorption therapy was started after discontinuation of this drug, and was continued for 6 months, resulting in improvement of neurological symptoms and decrease in AchR Ab level. MG has not recurred since. Although several cases of D-penicillamine (DP) induced MG are reported, only two cases are reported which were induced by BU, sulfhydryl compound which has a structure similar to DP. Since BU has been widely used as one of the disease modifying anti-rheumatic drugs in Japan, MG induced by this drug should be paid attention as one of the adverse effects.
10415620 In vitro superfusion method to study nerve-immune cell interactions in human synovial memb 1999 Jun 22 Reports on patients with hemiparalysis indicate the importance of the nervous system for the pathophysiology of rheumatoid arthritis (RA) or osteoarthritis (OA). Norepinephrine (NE) and opioids seem to be more antiinflammatory neurotransmitters whereas substance P is proinflammatory. The study aimed to investigate the direct noradrenergic nerve-immune cell interaction in human synovial membrane. We used a recently developed superfusion technique with electrical stimulation of synovial membrane to elicit local NE from synovial membrane slices. The readout parameter of synovial immune cells was interleukin-6 (IL-6). IL-6 was spontaneously secreted from RA and OA synovial membranes. Electrical field stimulation intensively reduced IL-6 secretion. In patients with OA or RA, this electrically induced reduction of IL-6 secretion was not significantly changed by alpha- or beta-adrenergic antagonists. The study demonstrates that local endogenous NE seem to play a minor role, which may be due to a depletion of NE or loss of noradrenergic fibers during chronic RA and OA.
9489813 Longterm prospective study of methotrexate in rheumatoid arthritis: conclusion after 132 m 1998 Feb OBJECTIVE: To conclude observations of efficacy of longterm methotrexate (MTX) treatment of rheumatoid arthritis (RA). METHODS: Twenty-six patients with RA entered a prospective study of MTX in 1983. The study was completed after 132 months of therapy. RESULTS: Significant improvement (p < 0.001) was noted in the number of painful joints, swollen joints, and physician and patient global assessments. There was 50% improvement in the joint pain index and joint swelling index in > 65% of the patients. A significant reduction in prednisone dose was achieved. Sixteen patients withdrew from the study. Toxicity led to 3 drug related withdrawals of study patients (alopecia 1; pneumonitis 2). At 132 months, 10 patients (38%) had completed the study; 3 patients (11%) discontinued due to MTX toxicity. CONCLUSION: MTX was an effective treatment for RA in this 132 month prospective study.
9801344 Human T-cell lymphotropic virus type 1 tax among American blood donors. 1998 Nov In the United States, all blood used for transfusion is tested for the presence of antibodies to the structural components of the human T-cell lymphotropic viruses types 1 and 2 (HTLV-1 and -2). Based on such serologic tests, the prevalence of HTLV-1 infection is estimated to range from 0.016 to 0.1%. As a consequence of studies of patients with mycosis fungoides and some of their healthy relatives who are antibody negative but were found to carry the tax sequence of HTLV-1 in their lymphocytes and who had antibodies to the p40(tax) protein, a study was undertaken to determine the prevalence of the "tax-only" state in 250 healthy blood donors and other volunteers. Using PCR and Southern analysis for cell lysates and using Western blotting for plasmas, 8.6% of the blood donors proved to be tax sequence positive and antibody positive. Sequence analysis of specimens from 22 individuals proved that 20 of the sequences were homologous with that of HTLV-1 while 2 resembled the HTLV-2 sequence. The latter were obtained from volunteers of Indian origin. The possible clinical significance of the tax-only carrier state is discussed.
10520307 [Abdominal actinomycosis after stomach surgery in a patient with long-term rheumatoid arth 1999 Sep 17 HISTORY AND ADMISSION FINDINGS: A 78-year-old woman had a 30-year history of rheumatoid arthritis, of late treated with prednisolone and methotrexate. A week before admission she had first noticed a mass about 3 cm in diameter, at the lower end of a scar from a Billroth II gastric resection for gastric ulcer, performed 4 months before. She reported to have lost 6.5 kg in weight. On admission a moderately mobile, hard mass was palpated on the abdomen. INVESTIGATIONS: Ultrasound and computed tomography revealed a superficial, inhomogenous space-occupying lesion with poorly circumscribed margins. TREATMENT AND COURSE: After two days the skin over the mass became reddened and a laparotomy was performed because an incarcerated herniation was suspected. An abscess and inflammatory adhesions were found in the area of the transverse colon, histologically shown to be a chronic purulent abscess with granular clusters of pathogens indicating actinomycosis. After 3 weeks' treatment with imipenem i.v. the patient became free of symptoms, oral doxycyclin was continued for a further 6 months. CONCLUSION: Actinomycosis should be considered in the differential diagnosis of a tumour of undetermined benignity in the region of the head, chest or abdomen in immunosuppressed patients. This bacterial infection should be thought of especially if the gastrointestinal mucosa has been penetrated by invasive procedures.