Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 8396491 | Interference with the cortisol axis by the microtubule antagonist, CPH82. | 1993 Sep | Treatment with CPH 82, a mixture of two benzylidated podophyllotoxin glycosides, has been shown to improve inflammatory activity in patients with RA. The drug has few side effects but some patients have developed clinical features of Cushing's syndrome. We studied the hypothalamic-pituitary-adrenocortical axis in two female patients before and during treatment with CPH82. The results clearly demonstrate that CPH82 was associated with suppression of the endogeneous production of ACTH and cortisol with a concomitant paradoxical picture of clinical hypercortisolism. These observations suggest that CPH82 has glucocorticoid receptor agonistic effects. | |
| 8252317 | Sleep disturbances in patients with primary Sjögren's syndrome. | 1993 Dec | A standardized sleep questionnaire was used to investigate the sleeping habits of outpatients with primary Sjögren's syndrome (pSS) (n = 40) and RA (n = 42). Sleep deficit (difference between need of sleep and actual sleeping time) was significantly higher in patients with pSS when compared with healthy matched controls (P < 0.0001), and with patients suffering from RA (P < 0.001). When trying to fall asleep, patients with pSS were significantly more often disturbed by muscular tension (45%) and restless legs (24%), than patients with RA (12%, P < 0.01 and 2%, P < 0.01), and they were also significantly more troubled by nocturnal pain than patients with RA (P < 0.01). The pSS group reported significantly more disturbing by awakening during the night and was awake for longer periods than the RA group. Fatigue was a significantly more frequent complaint in patients with pSS. Polysomnography showed that all recorded patients (n = 10) had some sleep disturbances; reduced sleep efficiency (n = 8), increased number of awakenings (n = 5) and increased wakefulness surrounded by sleep (n = 9). Five patients had alpha intrusion in their sleep EEGs. The sleep disturbances seen in patients with primary Sjögren's syndrome may contribute to the fatigue associated with this disease. | |
| 8839464 | Threaded steinmann pin fusion of the craniovertebral junction. | 1996 Jul 15 | STUDY DESIGN: In a clinical retrospective study, the authors review long-term results of occipitocervical fusion using a wide diameter, contoured, threaded Steinmann pin. OBJECTIVES: To evaluate the clinical and radiographic results of occipitocervical fusion using this technique in a variety of abnormalities including rheumatoid arthritis. SUMMARY OF BACKGROUND DATA. The various surgical techniques and hardware developed for occipitocervical fusion have been associated with mixed results, particularly in patients with rheumatoid arthritis or basilar invagination. METHODS: Thirty-nine patients with occipitocervical instability were internally fixed with a wide diameter, contoured, threaded Steinmann pin wired to the occiput and cervical laminae or facets. Fusion was facilitated using autologous iliac crest bone graft and a cervical orthosis. Instability resulted from rheumatoid arthritis (n = 12), congenital anomalies (n = 12), trauma (n = 10), tumor (n = 4), or osteogenesis imperfecta (n = 1). Fifteen patients had radiographic evidence of basilar invagination. Long-term outcome (mean follow-up period, 38.9 months; range, 12-78 months) was based on clinical and radiographic review. RESULTS: Thirty-seven patients (97%) had a stable postoperative occipitocervical construct: there were 35 osseous unions, two fibrous unions, and one nonunion. There was on postoperative death from pulmonary complications. No patient developed evidence of new, recurrent, or progressive basilar invagination. CONCLUSION: The authors concluded that rigid segmental fixation of the craniovertebral junction using a wide diameter, contoured, threaded Steinmann pin and supplemental autograft creates excellent fusion with minimal complications. This technique is appropriate for a variety of abnormalities including rheumatoid arthritis. | |
| 1595007 | [Ulnar nerve palsy in a RA patient after total knee replacement: a case report]. | 1992 Apr | A 49-year-old housewife had suffered from classical seropositive rheumatoid arthritis for 24 years. The shoulders and hands were involved but the most severs pain and deformity were in both elbows and knees. Consequently, she was unable to sit on wheel chair and was confined to a bed. And then, she was admitted to the Chiba Rehabilitation Center in September, 1986 for bilateral total knee replacement. In April 1987, she had an operation upon the right knee and in June, she had an operation upon the left knee. About 6 weeks after surgery, she felt numbness in bilateral hands. The diagnosis was cubital tunnel syndrome. This was confirmed by electromyographic studies. Surgical release was undertaken without delay. The day following operation the patient remarked on the absence of numbness in bilateral hands. | |
| 8832992 | Citrate in synovial fluid and its relation to inflammation and crystal presence. | 1996 Mar | OBJECTIVE: To investigate the role of citrate in the pathophysiology of arthritides with calcium pyrophosphate dihydrate (CPPD) crystals and/or apatite-like material. METHODS: We measured citrate concentrations in the plasma and synovial fluid (SF) of 23 joints whose SF contained these crystals and 33 joints without crystals. The SF originated from 25 joints each of patients with rheumatoid arthritis (RA) and primary osteoarthritis (OA) and 10 patients with various other inflammatory joint diseases. RESULTS: There was significant correlation between citrate concentrations in the SF and plasma with values globally twice as high in the SF as in the plasma. Citrate concentrations in the SF of patients whose SF contained CPPD crystals and/or apatite-like material were not significantly lower than those without crystals. On the other hand, citrate concentrations were significantly lower in the SF of patients with RA and other inflammatory joint diseases versus those with OA. CONCLUSION: We have no evidence that lower amounts of citrate in SF favor the presence of CPPD crystals or apatite-like material. Our results, however, do suggest a complex regulation of the citrate concentration in SF where cellular metabolic processes and citrates arising from the plasma and neighboring tissues probably interact to produce the levels recorded. | |
| 8620295 | Adhesion of rheumatoid lymphocytes to mucosal endothelium: the gut revisited. | 1996 Mar | By a study of the adhesion of rheumatoid mononuclear cells, we have sought to clarify the homing properties and origins of cells likely to be involved in the pathogenesis of this disease. The adhesion of mononuclear cells from patients with rheumatoid arthritis (RA) was enumerated by an in vitro adherence assay using frozen sections of endothelium-containing gut lamina propria (EGLP) from porcine small intestine. Preliminary studies verified the involvement of known adhesion molecules by inhibition assays using monoclonal antibodies Meca-367, Mel-14 and Hermes-3. Twenty-five paired samples of peripheral blood (PB) and synovial fluid (SF) were studied, plus six from synovial membrane (SM) and eight from patients with other diseases. There was a significantly greater degree of adherence to EGLP by SF cells than PB (mean adherence 266 +/- 22 cells/mm(2), compared to 136 +/- 13 cells/mm(2), respectively, the majority of which were CD8+ cells; P=0.02, Mann-Whitney U-test for 25 paired samples). The results of the monoclonal antibody inhibition assays were in keeping with the involvement of homing receptors to gut endothelium in our assay system. Synovial fluid lymphocytes from RA patients exhibited adhesion properties more in keeping with lymphocytes of mucosal than of lymph node origin. Synovial membrance lymphocytes, by contrast, showed poor adherence to endothelium-containing lamina propria. The gut, as an immune lymphoid organ, may thus play a contributory role in this disease, possibly through the pathological seeding of cells into the synovial space. | |
| 8189646 | [A case of interstitial pneumonia antedating rheumatoid arthritis--differentiation from id | 1994 Mar | A 49-year-old female presented with productive cough, fever and chest pain, and was admitted to Nagoya University Hospital. Her chest X-rays, taken previously and on admission, showed infiltrative shadows in both upper lung fields and left-sided pleural effusion. Rheumatoid factors were positive in serum and the pleural effusion. Antibiotics were ineffective. Transbronchial lung biopsy revealed intraalveolar fibrosis as well as interstitial inflammation. Idiopathic BOOP was suspected on the basis of clinical findings together with the histological features. However, open lung biopsy revealed lymphoid hyperplasia with germinal center formation. The patient was diagnosed as having lung involvement antedating rheumatoid arthritis, despite the absence of joint symptoms at present. | |
| 1588740 | [Gold compounds and D-penicillamine for therapy of rheumatoid arthritis]. | 1992 Mar | Rheumatoid arthritis is a severe disease and it is difficult to prevent the progression of disease. Gold compounds (injectable gold and oral gold) and D-penicillamine (D-PA) have the possibility to retard joint destruction and to slow radiological progression. These drugs are called Disease Modifying Antirheumatic Drugs (DMARD), and they should be tried in cases resisting conventional NSAID's therapy. They are effective in more than 60% in severe rheumatoid patients but they also have many side effects, e.g. eczema, skin rash, renal dysfunction, aplastic anemia. Laboratory checks should be carried out once a month during the first six month, and every 2 or 3 months thereafter. To compare injectable gold with D-PA, discontinuation due to inefficacy of D-PA is higher than with injectable gold, but side effects of injectable gold is greater. Oral gold is less effective than the other 2 drugs, but has a lower rate of side effects. | |
| 1729804 | Diagnostic efficacy of digitized images vs plain films: a study of the joints of the finge | 1992 Feb | Four hundred fifteen finger joints from 30 patients were evaluated for the presence of joint-space erosion, narrowing, and degenerative spurring on plain films, low-resolution digitized images (1024 x 840 bytes x 12 bit matrix), and high-resolution digitized images (2048 x 1680 bytes x 12 bit matrix). Three hundred four joints were abnormal. Low- and high-resolution digital images were displayed on a 1K x 1K monitor with the ability to change level, window, orientation, and brightness. Five radiologists interpreted images. The presence or absence of each abnormality was determined by consensus of two skeletal radiologists who did not otherwise participate in the study. Receiver-operating-characteristic analysis was used to obtain an area and a true-positive rate at a 0.10 false-positive rate for each interpreter. Randomized block analysis of variance with interpreters as blocks was used to compare areas and true-positive rates among imaging techniques for each type of abnormality; no statistically significant differences were found. In conclusion, the efficacy of display of digitized images on high- and low-resolution modes is not significantly different from that of plain films in the detection of erosions, joint-space narrowing, or degenerative spurring in small joints of the hands. | |
| 8356250 | The need for aggressive therapy of rheumatoid arthritis. | 1993 Feb | We are on the threshold of a new era in the treatment of RA if we learn from the experience of the past and utilize new techniques and therapeutic modalities that the future will bring. New strategies and treatment of RA in the future will need to include earlier recognition of progressive disease, earlier interventions, new preparations for use in therapeutic armamentarium, combinations of agents, and monitoring of long-term outcomes to assess results over 5 to 10 years. There is always concern about new therapies and strategies. As noted by Huskisson, however, "In the absence of knowledge about the cause of disease and the mode of action of the drugs, the only way forward is by clinical trials of different preparations. With trial, there is always the risk of error." Our greatest error, however, will be if we ignore lessons from the past, fail to control the inflammatory process early, and continue to spend years writing "doing well" in the charts of patients who become progressively disabled before our eyes. | |
| 8162466 | Six-year follow-up of multiple joint replacement surgery to the lower limbs. | 1994 Jan | We report a 6-yr follow-up study of an original population of 50 patients who had three or more major joints (hips and knees) replaced. Thirty-one of 32 surviving patients were still ambulant in the community, and all patients described significant pain relief. No RA patient was requiring permanent inpatient or residential care and the family remained the main social support. They remained a very disabled group with a median Health Assessment Questionnaire score of 2.75. Ten required revision surgery: three hips and seven knees; four patients required their fourth lower limb joint (hip/knee) replaced and seven patients required surgery to the upper limbs and nine feet during the follow-up period. The median 10-yr survival of hip and knee arthroplasties in multiple joint replacement (MJR) patients with RA was 90.5 and 78.6% respectively. There was an increased incidence of cervical myelopathy in MJR patients 16.9%. The mortality rate was higher than expected (standardized mortality ratio = 590) but the actual surgery was not implicated. MJR therefore appears to be a worthwhile policy, even at long-term follow-up. | |
| 8575840 | Mycobacterium tuberculosis antigen, interleukin 2 and interleukin 2 inhibitor in patients | 1995 Nov | IL-2 production by the phytohemaglutinin (PHA)-stimulated mononuclear cells (MNC) of peripheral blood (PB) and synovial fluid (SF) from patients with rheumatoid arthritis (RA), other arthritic diseases (OAD) and age-matched normal controls were studied, and the activity of IL-2 inhibitor in sera of studied subject was examined. The significant decreased IL-2 production by PB MNC from the patients with RA (p < 0.05) and OAD (p < 0.05) were observed when compared with normal controls, and no statistical difference was found although IL-2 levels in RA PB were lower than in OAD PB. However, significant statistical difference (p < 0.01) was found when the IL-2 production by RA SF was compared with OAD SF. Serum IL-2 inhibitory factor was examined by IL-2-dependent mouse helper T cell line (HT-2). Significantly higher inhibitory activity was found in RA patients (p = 0.001) compared to OAD and normal control patients. Mycobacterium tuberculosis (MT) antigen was also examined from patients with RA and OAD, and 55.5% of SF from RA patients were positive for MT antigens and none was detected in OAD by a highly specific and sensitive double-antibody sandwich ELISA. However, no correlation between MT antigens, IL-2 levels and IL-2 inhibitory activities were found in patients with RA. Our results and other indicate that rheumatoid SF MNC, IL-2 inhibitor and MT antigen may play important roles in the pathogenesis of RA. | |
| 8871838 | In vitro effects of methotrexate on polyamine levels in lymphocytes from rheumatoid arthri | 1996 Jul | OBJECTIVE: Several studies have documented increased levels of polyamines in rheumatoid arthritis (RA). We have suggested that one of the mechanisms of action of methotrexate (MTX) involves the inhibition of polyamine synthesis in lymphocytes. In this study, we sought to establish the inhibitory effect of MTX on polyamine synthesis and its specificity. METHODS: Polyamine levels were determined in stimulated RA lymphocytes incubated in vitro with MTX and compared to levels in lymphocytes incubated with hydrocortisone, D-penicillamine, or medium alone. Lymphocyte polyamine levels were correlated with IgM-rheumatoid factor (RF) synthesis. RESULTS: Incubation with MTX resulted in concentration-dependent decreased intracellular levels of spermidine and spermine, while putrescine levels were not affected. Addition of folinic acid or S-adenosyl-methionine (SAM) prevented this MTX-induced inhibition. Incubation with D-penicillamine or hydrocortisone had no significant effect on polyamine levels. There was a positive correlation between intracellular polyamine levels and the inhibition of IgM-RF synthesis by MTX. CONCLUSION: These data suggest that MTX inhibits the synthesis of spermidine and spermine in stimulated RA lymphocytes through inhibition of the SAM-dependent pathway. This inhibition may be related to the immune-modulating properties of MTX. | |
| 1516260 | Oestrogen-induced suppression of collagen arthritis; 17 beta-oestradiol is therapeutically | 1992 Sep | The F1 hybrid mouse strain, from B10Q and DBA/1 parentals (the QD strain), is highly susceptible to induction of type II collagen-induced arthritis, an experimental model for rheumatoid arthritis. Males are more susceptible than females. Oophorectomy enhances susceptibility to arthritis and treatment with physiological doses of 17 beta-oestradiol (E2) suppresses disease. E2 treatment lowers the incidence of arthritis also in non-castrated and castrated males, showing that the anti-arthritic effect by oestrogen is not dependent on either sex hormone imprinting effects or interference with male sex hormones. Testosterone treatment of normal females, but not of castrated females, exaggerated development of the disease. In the testosterone-treated normal females, the oestrogen effect on vaginal smear was abolished and ovarian weight decreased, suggesting that the testosterone-mediated enhancing effect is caused by inhibition of ovarian oestrogen production. The crucial importance of oestrogens for the development of arthritis is focused on the effectiveness of treatment with gestation-related doses of E2 of normal, non-castrated females. | |
| 8853169 | The rheumatoid knee before and after arthrocentesis and prednisolone injection: evaluation | 1996 Jul | In patients with rheumatoid arthritis, intraarticular injection of corticosteroids is an accepted means of treating a symptomatic joint. It has previously been impossible to precisely quantitate the effects of these injections on synovial effusion and pannus. Magnetic resonance imaging (MRI) is a safe, effective means of evaluating joint anatomy, and the use of intravenous gadolinium (Gd)-containing contrast allows clear differentiation of fluid from abnormal synovial tissue. The current study utilized MRI and Gd-labeled diethylene-triamene pentacetic acid (Gd-DTPA) contrast to evaluate serial changes in 6 knees of 6 patients with rheumatoid arthritis, following arthrocentesis and intraarticular injection of prednisolone. One week after the corticosteroid was injected, 2 patients had reduction of pannus width to 20% and 68% of baseline measurements. In these same individuals, follow-up sagittal views showed decreases of total effusion and fluid-plus-pannus width. The other 4 patients, who were followed for 4 weeks, had minimal changes in fluid and synovium. Gd-DTPA-enhanced MRI permits precise assessment of effects of intraarticular injections on synovial fluid and pannus in the rheumatoid knee. | |
| 8216397 | Chimeric CD4 monoclonal antibody cM-T412 as a therapeutic approach to rheumatoid arthritis | 1993 Oct | OBJECTIVE: To investigate the effects of chimeric CD4 monoclonal antibody cM-T412 treatment in patients with rheumatoid arthritis (RA). METHODS: Thirty-two RA patients received daily doses of 10, 50, or 100 mg of cM-T412 intravenously for 7 days. RESULTS: There was a sustained decrease in the number of CD4+ T lymphocytes in all patients. Those who received 50 mg and 100 mg of the antibody experienced significant reductions in disease activity. CONCLUSION: Treatment with cM-T412 appears to have a dose-dependent beneficial effect in RA patients. The clinical effects of cM-T412 are independent of the depressed numbers of circulating CD4+ T cells. | |
| 8165444 | The effect of azathioprine on serum levels of interleukin 6 and soluble interleukin 2 rece | 1994 | Cytokine pathways are central to the perpetuation of synovial inflammation in rheumatoid arthritis (RA). Azathioprine (AZA) has disease modifying activity in RA. This study addressed the effect of AZA on serum IL-6 and soluble IL-2 receptor (sIL-2R) levels in RA. Over a 24 week period of therapy significant clinical improvement was observed. However, serum levels of both IL-6 and soluble IL-2R levels did not significantly change after AZA therapy. AZA therapy did not significantly alter the peripheral blood monocytes ability to produce IL-6 in vitro, either in the presence or absence of LPS. The mechanism by which AZA achieves clinical improvement in RA patients does not appear to be through IL-6 modulation or modification of synovial lymphocyte activation as assessed by serum sIL-2R levels. | |
| 8220920 | Amyloid arthritis associated with IgM kappa lymphoplasmacytoid lymphoma. | 1993 Nov | Amyloid arthritis is an uncommon cause of locomotor disease and may closely resemble RA. Macroglobulinaemia is rarely associated with amyloidosis and there has been only one report of amyloid arthritis in this setting, the patient having had Waldenstrom's macroglobulinaemia. We report the occurrence of amyloid joint disease in the course of an IgM kappa B-cell dyscrasia which evolved over 16 years to an overt lymphoplasmacytoid lymphoma. | |
| 7701526 | Comparison of antinuclear antibody and other immunohematological profiles among primary Sj | 1993 Dec | Sjögren's syndrome (SS) is currently classified into two groups (primary and secondary), because of differences in the disease in the two groups. We determined antinuclear antibody and other immunohematological parameters by using newer, more sensitive serologic methods on patients with primary SS, or secondary SS associated with rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE), and patients with just the systemic disease free of SS. This study defined both distinctive and common features between primary SS and each systemic disease: High titers of fluorescent antinuclear antibodies (FANAs), anti-SS-A/SS-B antibodies, and rheumatoid factors (RFs), as well as leukocytopenia were considered the main features of primary SS. Elevated levels of RFs and C-reactive protein were prominent in RA patients. In contrast, high titers of FANAs and anti-single stranded or anti-double stranded DNA antibodies, positive anti-ribonucleoprotein or Sm antibodies, leukocytopenia, and hypocomplementemia were characteristic for SLE. Furthermore, patients with secondary SS plus RA or SLE were found to have mixed features of SS and the associated systemic disease. The results strongly suggest that patients with secondary SS have two separate diseases, SS and the associated systemic disease. | |
| 8799515 | Effects of food and antacid on the pharmacokinetics of single doses of mycophenolate mofet | 1996 Jun | 1. Mycophenolate mofetil (MMF) is a prodrug of mycophenolic acid (MPA) and is being developed for the prevention of rejection following solid organ transplantation. This crossover study investigated the effect of food and antacid (Maalox TC) on the plasma pharmacokinetics of MPA and its inactive glucuronide metabolite MPAG after giving single 2 g MMF doses orally to rheumatoid arthritis patients. 2. With food, the AUC of MPA in plasma was equivalent to that following an overnight fast. MPA tmax was slightly delayed and Cmax was lowered about 25%, consistent with delay in gastric emptying in the fed state. MPAG Cmax and AUC were higher in the fed relative to the fasting state, suggesting more complex processes involving changes in glucuronidation may also be occurring with food. 3. With antacid, AUC of MPA was lowered about 15% compared with fasting and Cmax was decreased 37%. Plasma MPAG parameters were similarly reduced. These parallel changes in MPA and MPAG are consistent with reduced absorption. 4. The changes in MPA with both food and antacid are small in comparison with the interpatient variability and are not likely to have clinically major effects; the changes in MPAG are of mechanistic interest. |