HLA-DRB1 genes and disease severity in rheumatoid arthritis. The MIRA Trial Group. Minocycline in Rheumatoid Arthritis

OBJECTIVE: To examine the effect of alleles encoding the "shared"/"rheumatoid" epitope on rheumatoid arthritis (RA) disease severity in patients who participated in the minocycline in RA (MIRA) trial. METHODS: Of 205 patients with a week-48 visit, blood was available for typing of HLA-DRB1 and HLA-DQB1 in 174 (85%) and successfully completed in 169 (82%). Baseline erosions were used to assess disease severity and new erosions at the last visit served as a proxy for progression. RESULTS: At baseline, there was no association between the presence of erosive disease or rheumatoid factor status and the dose of rheumatoid epitope (homozygous, heterozygous, none) or the specific alleles identified. At the final visit, a gradient was observed for the 3 allelic subgroups (and their gene doses) in the occurrence of new erosions among the Caucasian placebo-treated, but not the minocycline-treated, patients. A treatment group/HLA-DR4 epitope interaction was demonstrated in multivariate analyses. Approximately two-thirds of African-American patients did not have the rheumatoid epitope. CONCLUSION: HLA-DRB1 oligotyping may be useful in predicting the progression of disease in some Caucasian patients. Our study corroborates the infrequency of the epitope among African-American patients with RA.     

Disturbances of affective prosody in patients with schizophrenia; a cross sectional study

The solutions of nine alpha, omega-bis(3-alkyl(aryl)-4,5-dihydro-1H-1,2,4-triazol-5-on-4-yl) alkanes were titrated with tetrabutylammoniumhydroxide (TBAH) in methanol, using potentiometric methods. The half neutralization potentials values were found for all cases. Potentiometric titration curves of compounds in methanol with 0.03 M TBAH are similar to those of weak acids obtained in aqueous media with strong bases. Methanol is found to be a suitable medium for the weakly acidic compounds titrated since they are poorly dissolved in other organic solvents. A comparison among the compounds having the same alkyl chains between the two ring systems has shown that basicity increases and acidity decreases as the size of alkyl chains increases. However, the compound with a substituted phenyl group was found to be the most acidic one among the examined compounds indicating that phenyl group donates ring electrons less effectively to the system. This can be attributed to the stability of the benzene ring.     

Long-term health outcomes and quality of life in American and Italian inception cohorts of patients with juvenile rheumatoid arthritis. I. Outcome status

OBJECTIVE: To assess the long-term health outcomes and quality of life of patients with juvenile rheumatoid arthritis (JRA) using health and functional assessment questionnaires in 2 populations, one from the USA and one from Italy. METHODS: Patient eligibility criteria: (1) first examined in our units between 1958 and 1990 during the first 6 months after onset of symptoms, (2) diagnosis of JRA by the American College of Rheumatology criteria, (3) disease duration of at least 5 years at the time of assessment of outcome. Instruments used: (1) the Health Assessment Questionnaire (HAQ, short form, or childhood HAQ (CHAQ), and (2) Quality of Life Scales (QOLS, adults only). Eligible patients were identified by computer search and chart review and were then mailed a packet containing a consent/assent form and the assessment instruments. RESULTS: Of 346 patients who met the eligibility criteria were able to locate 301, and 290 verbally agreed to participate and were mailed packets. Signed consent and complete information were received from 227 of the 290 (78%), 178 from the USA and 49 from Italy. Mean duration of disease at the time of outcome assessment was 15 yrs. 127 had pauciarticular, 55 polyarticular, and 45 systemic onset disease. Mean and (median) scores of the outcomes are shown in the table. [table: see text] CONCLUSION: Long-term outcome, as assessed by the instruments used, is very favorable in most patients with JRA 5 years or more after onset of symptoms.     

Total wrist arthroplasty in rheumatoid arthritis. A long-term clinical review

Fourteen total wrist arthroplasties performed in 13 patients with rheumatoid arthritis between 1978 and 1982 were reviewed to evaluate long term outcome. Most patients had Stages III or IV rheumatoid arthritis at the time of surgery. Pain was the primary presenting complaint in 87%. Average followup was 6.5 years (range, 3.5-11.5 years). Pain relief was achieved in 86% of patients. Using objective data obtained from their wrist scores, 72% of the patients had a good result, 14% had a fair result, and 14% had a poor result. No patient had an excellent result. Twenty-seven percent suffered postoperative complications related to their surgical procedure. Although these results help confirm the usefulness of total wrist arthroplasty as an alternative to arthrodesis of the wrist, it is a technically demanding procedure, and should be reserved for the patient who has severely involved arthritis. Additional improvements are needed to decrease the currently high complication and failure rate.     

Salsalate, a nonacetylated salicylate, is as efficacious as diclofenac in patients with rheumatoid arthritis. Salsalate-Diclofenac Study Group

OBJECTIVE: To investigate the efficacy of salsalate, a nonacetylated salicylate, in the treatment of patients with rheumatoid arthritis (RA). METHODS: Three hundred and one patients meeting the ACR criteria for RA were drawn from 16 centers. After withdrawal of nonsteroidal antiinflammatory drugs (NSAID) and subsequent flare, patients were randomized to receive either salsalate or diclofenac for 8 weeks, according to a double blind, double dummy protocol. Initial doses of salsalate 3.0 g/day and diclofenac 75 mg/day were titrated for the first 5 weeks. The primary outcome measure was a multivariate analysis at 8 weeks of tender joint count, pain, visual analog scale score, and physician's global assessment. RESULTS: One hundred and ninety patients completed the study. The mean stabilized dose of salsalate was 3.55 g/day, and that of diclofenac 112 mg/day. Discontinuations were due to lack of efficacy (17 salsalate vs 15 diclofenac); adverse events [19 salsalate (mainly tinnitus and hearing loss; p = 0.0001 and p = 0.04, respectively) vs 9 diclofenac]; laboratory abnormalities (3 salsalate vs 1 diclofenac); and other reasons, including protocol violations, intercurrent illness, and personal factors (24 salsalate vs 23 diclofenac). Both treatments produced significant improvement from flare (p < 0.0001). Post hoc power analysis showed that the study had sufficient power (0.60 to 0.90) to detect clinically important differences between the 2 drugs in the primary outcome measures; however, no statistically significant (p = 0.29) or clinically important treatment differences were recorded. Other than a difference in erythrocyte sedimentation rate that favored salsalate, there were no significant differences in secondary outcome measures between the 2 groups. All outcomes showed a tendency for more improvement with salsalate. CONCLUSION: Salsalate is as efficacious as diclofenac. Salsalate may be considered an alternative to other NSAID in the first line treatment of patients with RA.     

The assessment of functional status in rheumatoid arthritis: a cross cultural, longitudinal comparison of the Health Assessment Questionnaire and the Groningen Activity Restriction Scale

OBJECTIVE: To compare a disease specific measure of functional status, the Health Assessment Questionnaire (HAQ) with a generic measure of functional status, the Groningen Activity Restriction Scale (GARS) in a cross cultural and longitudinal setting. Besides the comparison of psychometric properties, sex differences were also studied. METHODS: In a sample of 634 patients with rheumatoid arthritis (RA) (290 from The Netherlands, 116 from France, 228 from Norway), the psychometric properties (Cronbach's alpha and rho) of the GARS and the HAQ were compared among countries. The sensitivity for change between T1 and T2 was tested by means of the standardized response mean for a one year followup; furthermore, the relative efficiency of both instruments was computed. A t test was used to trace sex differences. RESULTS: The psychometric properties of both the HAQ and the GARS were very good. Both form unidimensional scales of hierarchically ordered items; alpha and rho are > 0.91 for both instruments. For patients who improved between T1 and T2, measured by the Ritchie Articular Index, the standardized response mean of the HAQ and the GARS were moderate, whereas for patients who worsened, the standardized response means were small. The results based on the relative efficiency were ambiguous. Furthermore, the mean score for women on the HAQ was 0.25 higher in contrast to scores for men. The GARS did not yield different scores for women and men. CONCLUSION: The internal consistency of the GARS and the HAQ are comparable. The HAQ has yielded different results for women and men. Therefore, when the HAQ is used, sex differences should be taken into account. With respect to sensitivity to change, the GARS and the HAQ obtained much better results for patients who improved in contrast to patients who worsened. The GARS was found to be more sensitive to change for patients who improved.     

Joint destruction after glucocorticoids are withdrawn in early rheumatoid arthritis. Arthritis and Rheumatism Council Low Dose Glucocorticoid Study Group

OBJECTIVE: Prednisolone reduced the progression of joint destruction over 2 yr in early, active rheumatoid arthritis. The response to discontinuation of prednisolone under double-blind conditions is now reported. METHODS: A randomized, double-blind, placebo-controlled trial of prednisolone 7.5 mg daily in addition to routine medication over 2 yr in 128 patients with early rheumatoid arthritis, using radiological progression (changes in the Larsen score) and the development of erosions as primary outcome measures. Study medication was blindly discontinued and follow-up maintained for a further year. Other assessments included disability, joint inflammation, pain and the acute-phase response. RESULTS: Similar results were obtained when all available radiographs were included for each year of assessment (maximum 114) and when only patients with radiographs at all time points were included (75 patients). In these 75, the mean progression in the prednisolone group was 0.21 Larsen units in year 1, 0.04 units in year 2 and 1.01 units in year 3 (P = 0.587, 0.913 and 0.039 for change within each year, respectively). The equivalent placebo group means were 2.34, 1.00 and 1.63 Larsen units (P = 0.001, 0.111 and 0.012; difference between groups: 2.13, 0.96 and 0.67 units, P = 0.082, 0.02 and 0.622). The percentage of hands which had erosions at each time point was: prednisolone group: 27.8, 29.2, 34.7 and 39.2; placebo group: 28.2, 48.7, 59.0 and 66.5. There was little evidence for a flare in clinical symptoms after discontinuation of prednisolone. CONCLUSION: Joint destruction resumed after discontinuation of prednisolone. This corroborates the previously reported therapeutic effect and challenges current concepts of disease pathogenesis.     

Adaptation in patients with chronic rheumatoid arthritis: Application of a general model.

Derived a model of appraisal, coping, and adaptation in patients with rheumatoid arthritis (RA) from the more general theory of R. S. Lazarus and S. Folkman (1984) and examined this model using a longitudinal data set spanning 4 yrs and involving 239 RA patients. This model attempted to identify the short- and long-term adaptational consequences of coping as well as the antecedents (e.g., appraisals, beliefs, social support, disease activity) that promote particular coping styles. Interrelations among the variables were examined using path-analytic techniques. Many observed relations were consistent with the model. Analyses provided support for many observed relations and suggested the existence of a vicious cycle involving helplessness appraisals, passive coping with pain, and psychosocial impairment that promotes maladaptation in the face of RA. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Potential pathogenicity of deglycosylated IgG cross reactive with streptokinase and fibronectin in the serum of patients with rheumatoid arthritis

PURPOSE: Drug free and drug loaded protein-free low density lipoprotein (LDL) models consisting mainly of phospholipids, cholesterol, cholesterol esters, and triglycerides in ratios found for physiological LDL have been prepared. Their physicochemical characteristics were compared with those of physiological LDL. METHODS: Different characterization methods were used: photon correlation spectroscopy, transmission electron microscopy, X-ray solution scattering, and 1H nuclear magnetic resonance spectroscopy (NMR). RESULTS: Particle sizes are highly dependent on the preparation method and in particular on the homogenization conditions. Electron microscopy indicates that the size distributions of model systems are much broader than those of physiological LDL. The X-ray solution scattering patterns of the model systems display a temperature dependent maximum near 3.8 nm similar to that found in the patterns of physiological LDL. NMR indicates a comparable mobility of the lipid molecules in model particles and in physiological LDL. The influence of drug loading is similar to that found earlier for physiological LDL. In particular, the incorporation of the anti-cancer drug WB 4291 seems to have a fluidizing effect on the lipids in the core region of the particles. CONCLUSIONS: The preparation method of LDL model systems is of crucial importance as only the solvent evaporation method yielded systems in the size range of physiological LDL with acceptable high lipid concentrations. The fluidizing influence of temperature and drug incorporation (WB 4291) may be disadvantage in drug targeting.     

Methodological considerations in the refinement of clinical assessment instruments.

Instrument refinement refers to any set of procedures designed to improve an instrument's representation of a construct. Though often neglected, it is essential to the development of reliable and valid measures. Five objectives of instrument refinement are proposed: identification of measures' hierarchical or aggregational structure, establishment of internal consistency of undimensional facets of measures, determination of content homogeneity of undimensional facets, inclusion of items that discriminate at the desired level of attribute intensity, and replication of instrument properties on an independent sample. The use of abbreviated scales is not recommended. The refinement of behavioral observation procedures is discussed, and the role of measure refinement in theory development is emphasized. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Comparison of the MOS short form-12 (SF12) health status questionnaire with the SF36 in patients with rheumatoid arthritis

Cultured HL-60, HeLa S3 and WiDr cells grown in male BALB/c nu/nu mice were studied by conventional and field-inversion DNA gel electrophoresis (FIGE), as well as by means of cytomorphological approaches, including TdT-mediated dUTP nick end labeling (TUNEL) assay. Chemosensitivity tests revealed HL-60 to be sensitive to vindesine (VDS), and HeLa S3 and WiDr to mitomycin C (MMC). Although VDS-treated HL-60 exhibited condensation of chromatin and a DNA ladder, MMC-exposed HL-60 cells showed apoptotic figures without typical DNA ladders. With MMC-treated WiDr cells, neither DNA ladders nor apoptotic figures were observed. Cells characterized by chromatin condensation were TUNEL-positive in both treated and untreated cases with the exception of the MMC-treated WiDr case, in which many TUNEL-positive cells were observed without cytomorphological changes. On FIGE, DNA fragments of approximately 50, 300 and 400 kbp were detected in groups treated with both effective and ineffective drugs, as well as in untreated controls. Furthermore, change of the time parameters in FIGE resulted in different sizes (550 and 850 kbp) of DNA fragments. These findings indicate that i) cell death is not always detectable in terms of apoptotic figures or DNA oligonucleosomal fragmentation, ii) only the TUNEL assay is a reliable tool to detect DNA damage and, iii) FIGE does not provide accurate size profiles of macromolecular DNA fragments.     

Arthritis and perceptions of quality of life: An examination of positive and negative affect in rheumatoid arthritis patients.

The utility of measuring both positive and negative affective states for assessing rheumatoid arthritis (RA) patients was examined in 3 independent samples of male and female RA patients (Sample A: 179 women, 48 men; Sample B: 177 women, 24 men; Sample C: 134 women, 38 men). Confirmatory factor analyses of each sample indicated that positive and negative affect constituted separate, negatively correlated factors. The relations among disease variables, coping, and affects were consistent with a model in which coping mediates the relationship between disease variables and positive and negative affect. Patients with higher pain and limitation from RA had higher levels of maladaptive coping, and maladaptive coping was associated with lower positive affect and higher negative affect. Those RAs with higher activity limitation also reported less adaptive coping, which was associated with less positive affect. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Predictors of functional disability in patients with rheumatoid arthritis

The ability of nonactivated peritoneal macrophages to induce nitric oxide (NO) secretion in transformed and tumor cells of the same origin differing in tumorigenic (TGA) and spontaneous metastatic activities (SMA) was examined. Low tumorigenic and nonmetastatic spontaneously transformed in vitro hamster embryo cells of the STHE strain in contact with macrophages, or their non-purified soluble product were the highest producers of NO. In vivo selected STHE cell variants characterized by middle or high TGA demonstrated low, or no NO production, respectively (independently of SMA- or SMA+). Two highly tumorigenic RSV-SR (v-src) transformed cell strains (SMA- and SMA+) were both negative in NO production. Thus, NO production by tumor cells appeared to be inversely correlated with TGA level and less dependent on SMA.     

Analysis of pulmonary manifestations in patients with rheumatoid arthritis

We studied chest X rays of 911 patients with rheumatoid arthritis (RA). The findings showed interstitial shadow in 28 patients (3.1%), pleuritis in 13 patients (1.4%) and nodular shadow in 3 patients (0.3%). RA patients with interstitial pneumonia were commonly male and older. And they had significantly high levels of rheumatoid factor (RF), RAPA and IgG-RF in serum, but they were not associated with high score of Lansbary index. All patients with more than 1500 IU/ml in RF value had a complication of interstitial pneumonia. These results suggest the importance of chest X-ray in the management of RA patients with high titer in RF.