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ID PMID Title PublicationDate abstract
10908690 Interleukin-4 inhibits interleukin-11 production by rheumatoid synovial cells. 2000 Jul OBJECTIVE: To examine the effect of interleukin-4 (IL-4) on IL-11 production by rheumatoid synovial cells. METHODS: Freshly isolated rheumatoid synovial cells (FRS) were obtained by collagenase digestion of rheumatoid arthritis (RA) synovial tissue specimens taken at the time of operation. Rheumatoid synovial cells at four to eight passages were used as cultured rheumatoid synovial fibroblasts (RSF). IL-11 concentration was measured by ELISA. RESULTS: IL-4 inhibited the production of IL-11 by FRS in a dose-dependent manner. This inhibition was observed in FRS obtained from six patients, and the mean inhibition was 46.5%. The inhibitory effect of IL-4 on IL-11 production was cancelled by the addition of anti-IL-4 antibody. IL-4 also inhibited IL-11 production by IL-1alpha-stimulated cultured RSF. CONCLUSION: IL-4 inhibited IL-11 production by rheumatoid synovial cells. IL-4 has a protective effect on bone resorption. On the contrary, IL-11 participates in bone resorption via osteoclastogenesis. Therefore, IL-4 may exert its protective effect on bone resorption, at least in part, via inhibition of IL-11 production in rheumatoid joints.
11155795 Dynamic thermography of the knee joints in rheumatoid arthritis (RA) in the course of the 2000 Thermography in rheumatology is most often used in a static manner: after having fulfilled the conditions of standardized preparation of the patient in a cold examination room one or more thermograms are taken in standard positions for the respective joints. In our hospital the thermograms are more or less supplementary. The main examination result is a rewarming curve of the skin over the knee joints. The rewarming is provoked by dry cooling of the skin for one minute. Calculation of the slope of the rewarming curve and plotting the slope on a logarithmic scale shows two different rewarming processes in the skin overlying inflamed joints. The faster one is the rewarming by the arterial blood flow in the skin and the slower one is an additional rewarming by a pathological venous skin blood flow originating from deeper tissues under the skin. One has to suppose that the occurrence of excessive nitric oxide production in inflamed tissues is responsible for this pathological venous skin blood flow. Until now only nine patients receiving for the first time methylprednisolone could be included in a therapy study. Therefore only slight indications can be seen in the results. Whereas the erythrocyte sedimentation rate (ESR [mm/h] becomes more homogeneous (lower confidence interval CI 95) over the course of the treatment with decreasing drug dose, the thermal signs of inflammatory activity as measured by dynamic thermography have greater CI 95 values at the end than at the beginning of the treatment under study. This indicates that not all patients had sufficient antiinflammatory medication with the final 6 mg/d of methylprednisolone as measured by dynamic thermography but not by ESR or CRP.
9214070 [Volumes of synovial membrane and joint effusion determined by MR imaging. Markers of seve 1997 Jun 16 Volumes of synovial membrane and joint effusion were determined by MRI in 36 knees with gonarthritis and five healthy knees. In 18 knees MRI was performed before and immediately after arthrocentesis. The difference between MRI-determined and syringe-determined volumes of aspirated joint fluid was 0-7 ml, median 2 ml, corresponding to 0-18%, median 7%, of the pre-aspiration effusion volume. Synovial membrane volumes, determined before and after arthrocentesis varied 0-10 ml, median 3 ml (0-17%, median 7%). No significant systematic misinterpretation of the borderline between joint fluid and synovium was found. The interobserver variation was < 15% in all measurements of synovial volumes > 10 ml and effusion volumes > 5 ml. Patient repositioning resulted in variations < 10%. The synovial volumes in clinically active, clinically inactive and healthy knees were statistically significantly different (median 79 ml, 21 ml and 3 ml, respectively). We conclude that effusion volumes, and in all probability also synovial membrane volumes, can be determined by MRI with a maximal error of approximately 20%. The synovial volume is related to the inflammatory activity of the joint. The results encourage further studies of the value of effusion and synovial membrane volumes as markers of the activity and/or severity of joint inflammation.
10646487 Management of patients with newly diagnosed rheumatoid arthritis. 1999 Nov The traditional pyramidal approach to treatment of rheumatoid arthritis (RA) has the unfortunate effect of treating patients with early RA--those patients with the greatest potential for clinical response--with the least effective agents during the most prolonged and most damaging period of inflammation. Given the wide variety of therapies now available, and the fact that the disease itself can be more destructive than the toxicity of drug therapy, it is important to know the likely outcome for an individual patient so that therapy can be targeted accordingly. The rapid development of new imaging techniques has enabled joint damage to be assessed at a very early stage. The correlation of data obtained from these techniques with clinical data, such as the presence of rheumatoid factor and the shared epitope, may provide a basis on which therapies in the future can be tailored for individual patients.
10405932 The responsiveness of health status measures in patients with rheumatoid arthritis: compar 1999 Jul OBJECTIVE: To compare the responsiveness of 2 disease-specific questionnaires, the Modified Health Assessment Questionnaire (MHAQ) and the Arthritis Impact Measurement Scale (AIMS2) with corresponding dimensions (physical function, mental health, pain, and fatigue) in a generic health status measure [the MOS Short Form-36)] in patients with rheumatoid arthritis (RA). METHODS: Within the framework of an observational study, a prospective cohort of 595 patients with RA from a community based patient register responded to a questionnaire at baseline and after 2 years' followup. Changes in patient global disease activity assessed on a categorical verbal rating scale (range 1-5) were used as external indicator of improvement or deterioration. Responsiveness was evaluated with standardized response means (SRM), calculated as mean change score divided by the standard deviation of the mean change score. RESULTS: Changes in patient global disease activity were classified as much better (n = 33), slightly better (n = 108), no change (n = 291), slightly worse (n = 108), and much worse (n = 20). There were no significant differences in responsiveness between SF-36 and the disease-specific measures within the same dimensions of health. The SRM of the tools within the dimension of pain (AIMS2 and SF-36) were moderate (0.5-0.8) to large (> 0.8) consistently in both directions (improvement and deterioration). The physical function subscales detected the same pattern, but the magnitude of the gradients was smaller. The fatigue and mental health subscales did not show any clear and consistent pattern of change. CONCLUSION: In patients with RA, there was no difference in responsiveness of subscales from SF-36 and disease-specific instruments when using changes in patient assessed global disease activity as an external indicator of change in health status. The dimension of pain was most sensitive to changes in patient assessed global disease activity followed by physical function, fatigue, and mental health.
11114284 Short term effects of corticosteroid pulse treatment on disease activity and the wellbeing 2001 Jan OBJECTIVE: To investigate the short term effects of corticosteroid pulse treatment (CPT) on disease activity, functional ability, and psychological wellbeing of patients with active rheumatoid arthritis (RA). METHODS: Of 66 consecutive patients with active RA admitted for CPT, erythrocyte sedimentation rate, C reactive protein level, haemoglobin concentration, platelet count, duration of early morning stiffness, a joint score, and grip strength were assessed before and after CPT. Additionally, a health status questionnaire was administered. Effects of CPT were expressed as before to after intervention effect sizes and, to place them in perspective, compared with the (long term) effect sizes of disease modifying antirheumatic drug (DMARD) treatment in a historical contrast group of patients with early RA. RESULTS: Statistically significant improvement from baseline in disease activity, physical functioning, and psychological wellbeing after CPT was seen, with moderate to large effect sizes, resembling the effects seen after DMARD treatment. Neither depression nor psychosis occurred during and after CPT. CONCLUSION: Qualitatively and quantitatively the short term effects of CPT in patients with active established RA on various dimensions of health status resemble the long term effects of conventional DMARD treatment in patients with early RA. Psychological disorders do not seem to be common short term side effects of CPT in patients with active RA.
10556263 Radiographic joint space in rheumatoid acromioclavicular joints: a 15 year prospective fol 1999 Nov OBJECTIVE: To evaluate radiographically the acromioclavicular joint space in patients with long-term rheumatoid arthritis (RA). METHODS: A cohort of 74 patients with RA was followed prospectively for 15 yr. At the end point, 148 shoulders were radiographed with a standard method. The acromioclavicular (AC) joint space was examined from the radiographs with a method developed previously for population studies; the joint space was measured at its superior and inferior border, and the average of the two measurements, the integral space, calculated. RESULTS: Mean AC joint space in RA patients was 4.9 (S.D. 3.7), range 0-20.5 mm; 6.2 mm (S.D. 5.1) in men and 4.5 mm (S.D. 3. 0) in women. An AC joint space wider than 7 mm in men was found in 11 (31%) out of 36 joints and wider than 6 mm in women in 17 (15%) out of 112 joints. Joint space widening was associated (r=0.87, 95% CI 0.82-0.90) with increasing destruction (Larsen grading) of the joint and it seems to be an inevitable consequence of AC joint affection in RA. Joint space widening is more progressive on the caudal side because of the nature of the erosive destruction. Degeneration with joint space narrowing was observed in 8 (11%) patients (11 joints, 7%; three bilateral). CONCLUSIONS: The largest value of the joint space may be used when evaluating rheumatoid AC joint space. In RA patients, a joint space of >7 mm in men and >5 mm in women is a sign of destructive AC joint affection.
9330931 A cross sectional assessment of health status instruments in patients with rheumatoid arth 1997 Oct OBJECTIVE: To (1) validate the Short-Form Health Survey (SF-36) as a generic functional health status measure in patients with rheumatoid arthritis (RA); and (2) assess correlations between the SF-36 and other outcome measures used in the Minocycline in Rheumatoid Arthritis (MIRA) Trial. METHODS: We conducted a cross sectional analysis of the final visit outcome measures from the 48 week, multicenter, placebo controlled, double blind MIRA trial. Multitrait scaling analyses assessed convergent and discriminant validity and internal consistency reliability of the SF-36 in the study patients. Responses to comparable items on the SF-36 and modified Health Assessment Questionnaire (M-HAQ) regarding physical functioning were compared and questions from both instruments were also compared to other RA outcome measures. RESULTS: In patients with RA, the SF-36 had high internal consistency and reliability, high discriminant and high convergent validity. Moderate correlations were observed (r = -0.46 to -0.61, p < 0.01 in each case) for comparable items on the SF-36 and M-HAQ regarding dressing, walking, and bending. Joint tenderness score correlations with items on the M-HAQ and SF-36, and joint tenderness score correlations with the SF-36 scales were higher than for joint swelling scores. Physician and patient global assessments were most highly correlated (r = 0.58 and 0.66; p < 0.01, respectively) with the SF-36 bodily pain item. CONCLUSION: The SF-36 is a valid instrument for this RA population. The SF-36 correlates with the M-HAQ and the physician and patient global assessments. The usefulness of the SF-36 in measuring change in RA clinical trials requires testing in longitudinal studies.
9137321 Peripheral beta-endorphin in rheumatoid arthritis. A correlation with the disease activity 1997 Beta-endorphin is a neuroendocrine peptide, with morphine-like effects, produced by anterior pituitary, cells of the immune system, and synovial cells. The clinical significance of Plasma Beta-endorphin was investigated in a well characterized cohort of 20 RA patients and 10 healthy controls. Beta-endorphin extraction and concentration were carried out according to Wardlaw. Plasma Beta-endorphin assay was measured as described by Naber. Plasma Beta-endorphin levels in severe RA patients were significantly lower (16.1 +/- 6.2 pg/ml) than in mild RA patients (45.4 +/- 2.8 pg/ml), P < 0.0001. The mean serum levels of Beta-endorphin were also significantly lower in both RA groups than those in normal controls (62.1 +/- 5.7 pg/ml), P < 0.001. The results indicate that there is an inverse correlation with the plasma Beta-endorphin levels, the rheumatoid disease activity score, and the duration of RA. The depressed plasma Beta-endorphin in patients with RA may be used as an indicator of the disease activity.
11396102 Tumor necrosis factor-alpha blockade in the treatment of rheumatoid arthritis. 2001 May The use of TNF alpha antagonists in RA has been extremely instructive. They have taught us that selective targeting of a pathogenic element can provide substantial clinical benefit. They have reinforced the concept of TNF alpha as a pivotal cytokine in the pathogenesis of RA. Pharmacodynamic studies of TNF alpha antagonists have further clarified the pathogenic processes involved in the disease. TNF alpha antagonists have set a new therapeutic standard for RA. Indeed, they are one of the most important advances in the history of the treatment of the disorder. If clinical efficacy is sustained and the safety profile remains benign over the long term, TNF alpha antagonists may replace MTX as the gold standard and become the agent of choice for combination therapy in RA. Further studies are needed to clarify their ultimate position in the therapeutic algorithm.
10556260 Apocynin, a plant-derived, cartilage-saving drug, might be useful in the treatment of rheu 1999 Nov OBJECTIVE: To investigate whether apocynin, 1-(4-hydroxy-3-methoxyphenyl)ethanone, is able to diminish inflammation-induced cartilage destruction in rheumatoid arthritis (RA), studied in a human in vitro model. METHODS: Apocynin was added to cultures of RA peripheral blood mononuclear cells (PBMNC). Cartilage-destructive activity was determined by addition of culture supernatant to tissue samples of human articular cartilage. In addition, the proliferation of PBMNC, their production of tumour necrosis factor alpha (TN-Falpha), interleukin (IL)-1 and IL-10, and T-cell production of interferon gamma (IFN-gamma) and IL-4, as measures for T1 and T2 cell activity, were determined. RESULTS: Apocynin was able to counteract RA PBMNC-induced inhibition of cartilage matrix proteoglycan synthesis, while no effect on inflammation-enhanced proteoglycan release was found. The effect was accompanied by a decrease in IL-1 and TNF-alpha production by the MNC. No effect on T-cell proliferation was found, but the production of IFN-gamma, IL-4 and T-cell-derived IL-10 was strongly diminished. Most important, apocynin did not show any direct adverse effects on chondrocyte metabolism; on the contrary, it diminished the release of proteoglycans from the cartilage matrix. CONCLUSION: Apocynin in vitro inhibits inflammation-mediated cartilage destruction without having adverse effects on cartilage. The latter may be an advantage of apocynin over many other non-steroidal anti-inflammatory drugs. Therefore, apocynin might have an added beneficial effect in protecting RA patients from joint destruction.
9529776 Raised IgM antibodies to parvovirus B19 in juvenile rheumatoid arthritis. 1998 Jan To delineate the role of human parvovirus B19 in the etiopathogenesis of juvenile rheumatoid arthritis (JRA), IgM and IgG antibodies specific for parvovirus B19 surface protein antigen(s) were estimated in the sera using commercial ELISA kits. Sera of 69 JRA patients (median age 16 yr, male : female ratio 1.1:1) satisfying the criteria of American Rheumatism Association along with 26 sera of rheumatoid arthritis (RA) and 12 sera of healthy children as disease and normal controls respectively were screened. Of the 69 patients with JRA, 19 (27.5%), 35 (50.7%) and 9 (13%) were positive for IgM, IgG and both IgG and IgM antibodies respectively. Of the 26 disease control sera, 11 (42.3%) were positive for IgG antibodies while none had elevated IgM antibodies. Among 12 healthy controls, 7 (58.3%) were positive for IgG and 1 was positive for both IgG and IgM antibodies. Thus, a statistically significant proportion of children with JRA had evidence of parvovirus B19 infection.
10757027 Novel gene therapy for rheumatoid arthritis by FADD gene transfer: induction of apoptosis 2000 Mar Synovial cells in the rheumatoid synovium show abnormal proliferation, leading to joint destruction. Rheumatoid synovial cells express functional Fas antigen and are susceptible to Fas-mediated apoptosis. We have proposed the induction of apoptosis by Fas/Fas ligand system of proliferative rheumatoid synovium as a novel therapy for rheumatoid arthritis (RA). We have recently reported that Fas-associated death domain protein (FADD) plays a key role in Fas-mediated apoptosis of synovial cells in patients with RA. In this study, we determined whether FADD gene transfer could induce apoptosis of RA synoviocytes in vitro and in vivo. Transfection of FADD gene by adenoviral vector into cultured RA synoviocytes induced up-regulation of FADD expression and apoptosis. In addition, local injection of FADD adenovirus (Ad-FADD) eliminated synoviocytes in vivo by induction of apoptosis of proliferating human rheumatoid synovium engrafted in severe combined immunodeficiency mouse, which is the most suitable animal model of RA for the evaluation of treatment strategy in vivo. In addition, Ad-FADD-induced apoptosis was limited to cells of the synovium tissue and did not affect chondrocytes. Our results strongly suggest that FADD gene transfer can induce apoptosis of RA synoviocytes both in vitro and in vivo, suggesting that FADD gene transfer might be effective in the treatment of RA.
11333349 Chemokines and angiogenesis. 2001 May Chemokines mediate the ingress of leukocytes, including neutrophils and monocytes, into the inflamed synovium. Among the four known chemokine families, C-X-C and C-C chemokines seem to be of outstanding importance in this process. Angiogenesis, the formation of new vessels, is also important in the pathogenesis of rheumatoid arthritis. In this review, the authors discuss the role of the most important chemokines in the pathogenesis of rheumatoid synovitis. The most relevant angiogenic factors and angiogenesis inhibitors involved in rheumatoid arthritis are also discussed. Because certain chemokines may also play a role in neovascularization, chemokines and the process of angiogenesis are described in this context as well. Apart from discussing the pathogenic role of these factors, the authors also review the important relevance of chemokines and angiogenesis for therapeutic intervention.
10371274 5'-Nucleotidase as a marker of both general and local inflammation in rheumatoid arthritis 1999 May OBJECTIVES: To evaluate measurements of serum and synovial fluid 5'-nucleotidase (5'N) activity as a marker of general and local inflammation in arthritis, and to resolve a contradiction in the literature as to whether or not the activity of 5'N in the synovial fluids of rheumatoid arthritis (RA) patients is raised in comparison with that in the synovial fluids of other arthritis patients. METHODS: Assays for 5'N were carried out in the presence of inhibitors of other phosphatases, AMP deaminase and of 5'N itself. RESULTS: The 5'N activity in the synovial fluid of RA patients was both significantly higher (mean 1.7-fold) and had a greater variance than that in the synovial fluids of other arthritis patients, and the contradiction in the literature was resolved. There was a strong correlation between the 5'N activity in the sera of RA patients and their erythrocyte sedimentation rate. There was no significant correlation between the 5'N in the serum and synovial fluid for the RA patients, in marked contrast to the strong correlation between the two 5'N activities shown by the osteoarthritis patients. The 5'N activity was greater in the synovial fluid than in the serum for virtually all the patients, showing that it was being made locally. CONCLUSIONS: The 5'N activity in the serum (which came mostly from the liver) could be used as a marker of general inflammation, whereas the 5'N in the synovial fluid was mostly produced locally, and could be used as a marker of joint inflammation, particularly for the RA patients.
9683554 Poor expression of T cell-derived cytokines and activation and proliferation markers in ea 1998 Jul We compared the state of activation and proliferation of T cells in synovial tissue (ST) from rheumatoid arthritis (RA) patients in early and late stages of the disease to find out whether T-cell-driven immune responses vary during the course of the disease. ST was obtained from 12 patients with early RA (< 1 year) and 12 patients with longstanding RA (> 5 years). T cells and interferon-gamma (IFN-gamma)-positive cells were detected in ST using immunohistologic methods. To determine the percentage of T cells expressing the interleukin-2 receptor, IFN-gamma, or the proliferation associated antigen Ki-67, immunofluorescence double-staining techniques were used. The scores for the number of T cells and for the expression of IFN-gamma as well as the percentages of T cells expressing CD25, IFN-gamma, or Ki-67 in rheumatoid synovium were not dependent on disease duration. These results do not support the assumption that the responsiveness of T cells in ST of RA patients differs between early and late stages of the disease. The data indicate that at present no arguments exist that the effect of T-cell-directed interventions on synovial inflammation might vary in different stages of the disease.
10229394 A retrospective study using nail clippings of rheumatoid susceptible alleles of HLA-DRB1 a 1999 Apr OBJECTIVE: To evaluate whether the number of susceptible factors influences disease progression in Japanese patients diagnosed with early rheumatoid arthritis (RA). METHODS: Fifty-eight Japanese outpatients (46 female, 12 male; mean age 48.9 yrs) with early RA of less than one year after onset were enrolled in the study. The criteria for early RA (Japanese Ministry of Welfare) were used. DNA was extracted from fingernail clippings and the gene frequencies of HLA-DRB1 alleles were investigated. The degrees of progression of (1) clinical symptoms, (2) laboratory findings, (3) radiographic changes, and (4) magnetic resonance imaging score were analyzed by a comparison of the above at time of diagnosis and at final examination (an average of 14 months after the time of diagnosis). RESULTS: The frequencies of the susceptible factors (S: 0101, 0401, 0404, 0405, 1001, and 1402) were 17, 3.4, 0.9, 29, 0, and 0%, respectively. The progression of inflammatory autoimmune activity, erosion incidence, and synovial proliferation severity in the S/S group was significantly more rapid than that in the other groups. In the disease activity at each time, the difference between the S/S group and the S/N group was significant, as was that between the S/S group and the N/N group, but the difference between the S/N group and the N/N group was not significant. CONCLUSION: Haplotyping of HLA-DRB1 using the patient's nail clippings may be useful as a prognostic marker for disease progression in early RA.
11393661 Tumour necrosis factor 5' promoter single nucleotide polymorphisms influence susceptibilit 2001 Apr Tumour necrosis factor (TNF) plays a pivotal role in the pathogenesis of rheumatoid arthritis (RA) and it has been shown that the TNF-lymphotoxin (TNF-LT) region influences susceptibility to RA. To investigate the role of the TNF-LT locus further, inheritance of TNF 5' promoter alleles was determined in multiplex RA families. Six previously defined TNF promoter single nucleotide polymorphisms (SNPs) (-238, -308, -376, -857, -863, -1031) were observed in these families and in addition, a heretofore undocumented adenine (A) to cytosine (C) substitution at position -572 relative to the transcription start site was defined. TNF 5' promoter SNPs were found to co-segregate with specific TNF microsatellite haplotypes. In particular, the SNP -308A allele was found to be inherited with the TNF a2, b3, c1, d1, e3 (H2) microsatellite haplotype (P < 0.001) which had previously been found to be associated with RA in individuals heterozygous for the HLA-DR 'shared epitope' (SE). When the data were stratified by the presence of the SE with further stratification according to SE DR subtypes and analysed by transmission disequilibrium test (TDT) for which offspring were assumed independent, the -308A and -857T alleles were found to be associated with RA in patients carrying the SE (P = 0.0076 and 0.0063 respectively). The data were further stratified to analyse for association in individuals homozygous or heterozygous for SE alleles. Results showed that the -308A allele was significantly associated with RA susceptibility in individuals heterozygous for the SE (P < 0.001) with the significance only occurring in patients carrying HLA-DR4 (P < 0.001), while the -857T allele was significant in individuals homozygous for the SE (P = 0.0039). Further analysis using the pedigree disequilibrium test (PDT) which conservatively adjusts for all sources of familial correlation except that conferred by linkage disequilibrium still indicated a significant role for the -308A and -857T alleles. These data provide evidence that TNF promoter SNPs may play an independent role in RA susceptibility in specific immunogenetically-defined groups of RA patients.
9208075 The safety of weekly low dose oral methotrexate in an Oriental population with rheumatoid 1997 Mar A retrospective review of 50 oriental patients with rheumatoid arthritis treated with weekly oral methotrexate showed adverse events in 15 (30%) patients with 19 occurrences (38%) of leucopaenia (4%), pancytopaenia (2%), gastrointestinal symptoms (18%), hepatic transaminase elevation (6%), rash (2%) and infections (6%). The median duration of treatment with methotrexate was 11 months (range 1 to 105 months). Pancytopaenia occurred in 1 patient with renal failure. All adverse events resolved with cessation of therapy and on several occasions, despite continued therapy. Methotrexate was discontinued permanently in 2 and temporarily in 7 patients as a result of adverse events. No recurrence of adverse events was noted on restarting methotrexate therapy in patients with non life-threatening adverse events. No increase in adverse events was noted in 14 patients treated with a combination of methotrexate and anti-malarial therapy. We conclude that methotrexate was well tolerated by the Oriental patients with rheumatoid arthritis in our study and could be safely restarted in those patients with non life-threatening adverse events.
10092164 Hypothalamo-pituitary-adrenal axis and growth hormone axis in patients with rheumatoid art 1999 Rheumatoid arthritis (RA) is a systemic disease and is associated with cytokines (IL-1, IL-6, TNF-alpha) production. There is little information on hypothalamo-pituitary-adrenal (HPA) axis and growth hormone (GH) axis in the patients with RA. We have, therefore, investigated these systems in twenty patients with confirmed RA. Ten of the patients had active and 10 patients remitted RA. Serum cortisol, ACTH and GH levels were measured in the basal state and after insulin induced hypoglycaemia. Cortisol, adrenocorticotropic hormone (ACTH) and GH responses were impaired in 65%, 85% and 30% of the patients, respectively. The basal and peak hormone levels were similar between the patients with active RA and the patients in remission. These findings indicate that there is an impairment in HPA and GH axis in patients with active and remitted RA. The site of this impairment is probably hypothalamus and/or pituitary gland.