Predicting factors for severity of rheumatoid arthritis: a prospective multicenter cohort study of 172 patients over 3 years.

Rheumatoid arthritis may take an unfavourable course leading to rapid functional decline in a certain percentage of patients. Early identification of these patients is desirable. The aim of this study was to evaluate clinical and laboratory parameters for their value in the prediction of bad outcome. A total of 172 patients with early arthritis were followed for 3 years. Higher initial values for erythrocyte sedimentation rate, IgG and IgM rheumatoid factor, serum concentration of cartilage oligomeric matrix protein, Health Assessment Questionnaire score, Larsen score of feet, disease activity score, and swollen and tender joint count predicted worse outcome. An association with the presence of IgA rheumatoid factor or anti-cyclic-citrullinated peptide could not be established. We conclude that prognosis in an individual with rheumatoid arthritis depends on many factors. The determination of independent prognostic factors for progression of rheumatoid arthritis is a valuable tool in early arthritis to select patients for more aggressive therapy.

[Functional capacity and cartilage oligomeric protein (COMP) in serum of patients with maturity-onset polyarthritis]. / Funktionelle Kapazität und Cartilage Oligomeric Matrix Protein (COMP) im Serum bei Patienten mit Alterspolyarthritis.

OBJECTIVE: To compare late onset with adult onset rheumatoid arthritis. METHODS: Fifty-eight patients with late onset rheumatoid arthritis (LORA) were compared to 117 patients with adult onset rheumatoid arthritis (AORA) with respect to clinical and functional parameters. Furthermore, in 104 patients serum cartilage oligomeric matrix protein (COMP) was measured. Results were compared by means of ANOVA and possible influences of age, gender and clinical parameters were evaluated by Spearman rank correlation. RESULTS: Except a different distribution in gender (40% males in the LORA group) and a higher ESR, no differences could be found with respect to clinical parameters. However, a significantly higher HAQ score and significantly higher serum-COMP levels could be shown in the LORA group. HAQ scores correlated not only with disease activity parameters (C-reactive protein, disease activity score) but also with the age. Serum-COMP levels did show a correlation with the age as well, but not with disease activity. CONCLUSION: It is concluded that the higher serum-COMP levels in late onset rheumatoid arthritis could be due to concomitant osteoarthritic processes in larger joints, which are not symptomatic. The age dependence of the HAQ score is only weak, but may be the reason why patients with LORA show a worse functional capacity compared to patients with adult onset rheumatoid arthritis.

Long-term observation study of Austrian patients with rheumatoid arthritis.

We examined retrospectively in a long-term observation study the outcome of patients with RA in Austria. Eighty-one inpatients with definite rheumatoid arthritis (RA) completed a standardized clinical and laboratory examination 3-8 times between 1978 and 1999. The course of the disease was assessed by determining the disease activity score (DAS), 28-joint count (28 JC), 30 swollen joint count (30 SJC), proximal interphalangeal joint score (PIP), Ritchie index, Stoke index, Steinbrocker stage, and Larsen score. In a mean duration of follow-up of 10 years, we observed a statistically significant improvement in PIP, Ritchie index, Stoke index, and DAS. Steinbrocker stage and Larsen score increased significantly. A high percentage of the patients did not receive any disease-modifying antirheumatic drug (DMARD) within the first 2 years of disease. Of all drugs used, methotrexate (MTX) was continued longer than other DMARDs. The most frequent extra-articular manifestation was sicca syndrome. In our long-term follow-up, a change in treatment from the onset of the disease in the 1980s to a more aggressive treatment within the last decade could be observed. However, with respect to the significant increase in Steinbrocker stage and Larsen score as well, an early aggressive therapy is required. With respect to the association of ANA and extra-articular manifestations, elevated ANA should give rise to an exact organ screening. For the development of predictive factors for the outcome in patients with RA, it would be helpful to refer patients at risk to specialist care as soon as possible.

[Comparison between early and late inpatient rehabilitation measures after implantation of total hip endoprostheses]. / Vergleich zwischen frühen und späten stationären Rehabilitationsmassnahmen nach Implantation von Hüfttotalendoprothesen.

This study was aimed at answering the question of whether a four-week inpatient early rehabilitation programme, i.e. within the first two months following total hip replacement surgery, will have a favourable impact as compared to later-onset inpatient rehabilitation measures; a total of 219 patients was studied: 137 were admitted during the first two months post-op (group A), 45 within three to four months post op (group B), and 37 patients were admitted at a later date (group C). Assessments were carried out for pain, walking performance and self-help status (scores) as well as for mobility, gait patterns, walking aids, walking speed, and disablement. In group A patients, significant improvement was achieved for all of these parameters: at the end of the rehabilitation programme (2.4 months post-op) these patients already were more mobile than group B patients at the time of admission (3.3 months post-op). In group B, improvements were found for several parameters. At a later time, the natural healing process had brought about so good a baseline situation in the group C patients that no further improvement was possible. The 162 patients treated successfully, i.e. where score reductions occurred, had been admitted significantly (p = 0.0001) earlier (2.9 months post-op) than the remaining 57 patients (5.7 months post-op). Some 14 months after programme participation, follow-up examinations were possible for 90 patients of group A, and for 27 patients from groups B and C. Further significant improvements had occurred in group A patients only, notably relative to muscle strength and reduction of walking aids. It is concluded from our data that inpatient early rehabilitation will achieve the greatest effect and will substantially reduce the recovery phase with its mobility limitations and daily living handicaps.

[Evaluation of 2 questionnaires with reference to their suitability for self-evaluation of patients with gonarthrosis. A contribution to quality assurance in rheumatology]. / Untersuchung von zwei Fragebogen hinsichtlich ihrer Eignung für die Selbstbewertung durch Patienten mit Gonarthrose. Ein Beitrag zur Qualitätssicherung in der Rheumatologie.

Questionnaires are useful instruments to evaluate disability and handicap in patients suffering from rheumatic diseases. Most of the used questionnaires require a time consuming interview with the attending physician or medical health personnel. Two (Larson and Lequesne) well established questionnaires are available for osteoarthritis(OA)-patients. Since it would be desirable to have reliable patients self reporting questionnaires, we have tested the utility and validity of these questionnaires by comparing the results of patients self reports with the results obtained by medical health personnel (4 occupational- and physiotherapists) in the same patients (n = 52). The analysis of the questionnaires revealed that results obtained by the Larson technique gave very different (p < 0.01) global and detail scores as assessed by patients or medical staff. This difference of assessments was not influenced by the stage of arthrosis as defined by x-ray. The Lequesne questionnaires gave essentially similar results, with a significant difference between assessment of disease severity by patients in comparison to results obtained by medical staff. The results obtained by the 4 members of the medical staff did not differ significantly from each other. From our study it is concluded that neither the Larson nor the Lequesne questionnaire can be recommended for scientific use as a reliable patients self reporting evaluation of disease severity in osteoarthritis.

[Effect of inpatient rehabilitation measures on patients with total hip endoprostheses--evaluation 15 months after operation]. / Effekt von stationären Rehabilitationsmassnahmen bei Patienten mit Hüfttotalendoprothesen--Beurteilung 15 Monate nach der Operation.

159 patients were examined approximately 15 months after hip arthroplasty. 116 of these patients have had at that time point a postoperative 4 week hospital stay for rehabilitation. A score that considered pain at motion and at rest, maximal walking capacity and activity of daily living was used for evaluation. The preoperative conditions did not differ between patients that had their postoperative hospital stay for rehabilitation (n = 116) and those that did not (n = 43). The results at the time of examination were regarded as excellent (group 1; score 3) in 64 (40.3%) patients, as good (group 2; score 4) in 56 (35.2%) patients and as poor (group 3; score > or = 5) in 39 (24.5%) patients. The amount of patients with a hospital stay for rehabilitation was significantly (p = 0.025) higher in the patient groups with excellent or good results in comparison with the patients with poor postoperative outcome. The most excellent results were obtained in patients who had their rehabilitation within the first two months after surgery (p = 0.008). Apart from the above mentioned score the following-additionally assessed-parameters differed significantly between the 3 groups: hip mobility; pain elicited by pressure on the operated joint; pain in the contralateral hip or knee joints; consumption of analgetics; walking time for 15 meters; degree of handicap as assessed by the patient or the occupational therapist or the physician; coping with household activities (for females only). We conclude that a poor result of hip arthroplasty may be due not only to degenerative joint disease of the lower limbs but also (or in combination) to the lack of a postoperative hospital stay for rehabilitation.

Bronchoalveolar lavage in rheumatoid arthritis.

Bronchoalveolar lavage (BAL) was performed on 70 RA patients, 28 without extra-articular manifestations, nine with pulmonary involvement, 13 with sicca-syndrome, 20 with other extra-articular manifestations such as renal involvement, cutaneous vasculitis and rheumatoid nodules. Fifteen patients without rheumatic or pulmonary disease served as the control group. Compared with the control group RA patients showed a statistically significant increase of lymphocytes, especially of activated (DR+)T(CD3+)-helper (CD4+) cells, resulting in a significantly diminished percentage of alveolar macrophages, B(CD21+)-lymphocytes, T-suppressor (CD8+) cells and an increased CD4/CD8 ratio. This cell distribution pattern was more pronounced in RA patients with lung involvement with significant differences to the other RA patients with regard to lymphocytes, DR positive cells and CD4 positive/DR positive cells. It is concluded that these results indicate an altered balance of immunocompetent cells not only in the joints but also in the lung. The changes are more distinct if local manifestations can be diagnosed clinically.

Bronchoalveolar lavage and lung biopsy in rheumatoid arthritis. In vivo effects of disease modifying antirheumatic drugs.

Bronchoalveolar lavage (BAL) and histology of transbronchial forceps biopsy was performed in 59 patients with rheumatoid arthritis (RA) to evaluate the in vivo effects of disease modifying drugs (DMARD). All patients had no clinical pulmonary symptoms and there was no evidence of drug induced alveolitis. Patients were divided into 5 subgroups according to drug treatment: 9 patients taking chloroquine, 15 patients gold, 8 patients penicillamine, 8 patients methotrexate (MTX) and 19 patients not taking DMARD. Duration of DMARD regimen was more than 3 months. No patient was treated with corticosteroids. BAL results revealed an increased percentage of lymphocytes and a diminished proportion of alveolar macrophages in patients treated with gold, penicillamine, MTX and no DMARD. In contrast, patients receiving chloroquine had a normal distribution of lymphocytes and macrophages as seen in a control group of 15 persons. Patients taking MTX showed a normal distribution of T and B lymphocytes and DR positive cells, whereas patients receiving chloroquine, gold, or penicillamine had an elevated proportion of T lymphocytes and DR positive cells and a diminished percentage of B lymphocytes. The latter was also observed in patients not taking DMARD. The percentage of natural killer cells was significantly elevated only in the penicillamine group. Patients receiving gold had higher absolute values of CD3, CD4 and DR positive cells. Abnormal lung histology was associated with an increased percentage of lymphocytes and with higher DR positive cells in BAL. Patients not receiving DMARD had a significantly higher percentage (42.1%) of abnormal histologic features of lung tissue than patients receiving DMARD (17.5%).(ABSTRACT TRUNCATED AT 250 WORDS)

Lung involvement in rheumatoid factor-negative arthritis.

Bronchoalveolar lavage (BAL) was performed on 13 asymptomatic patients with sero (rheumatoid factor)-negative arthritis (SNA); (6 with peripheral psoriatic arthritis, 2 with axial psoriatic arthritis, 3 with ankylosing spondylitis, 2 with sacroiliitis). BAL revealed a significant decrease of neutrophil granulocytes and an increase of B-lymphocytes in patients with SNA in comparison with 64 patiénts with rheumatoid arthritis (RA; 24 seronegative, 39 seropositive) and 15 healthy controls. Patients with SNA and RA had a significant increase of lymphocytes, especially T, T-helper and activated cells. In addition patients with RA had a significant increase of natural killer cells and a lower percentage of alveolar macrophages and T-suppressor cells. Transbronchial biopsy was performed on 9 patients with SNA and on 59 patients with RA. Abnormal histologic features of lung tissue were observed in 4 out of 9 patients with SNA (2 with fibrosis, 1 with follicular lymphoid hyperplasia, 1 with desquamative interstitial pneumonitis). The abnormal lung histology in RA patients was more pronounced, however, the differences between SNA and RA were not significant. The data from BAL and histology suggest, that the pulmonary involvement in SNA and RA is caused by an unspecified immunologic process.

[Rehabilitation after lumbar intervertebral disk operation]. / Rehabilitation nach lumbaler Diskusoperation.

122 patients were admitted 3 months after a lumbar disc operation to a rehabilitation clinic. Conservative treatment during the rehabilitation induced a decrease of low back pain (70 out of 107 patients), of paresis (30/51 patients), and of paresthesia (51/77 patients). More than 20 pre- and post-operative variables were tested with a rank-variance analysis regarding a possible influence on efficacy of the rehabilitation treatment. The success of the conservative treatment measured by improvement of paresis, paresthesia, pain and mobility of lumbar spine was influenced favourably by preoperative paresis (p less than 0.03). Women showed more often than men an improvement of paresis (p = 0.006) immediately after surgery. Patients with a preoperative paresis had a shorter history of radicular symptoms (p = 0.002), an acute onset was seen more often in patients with persistent paresis (p = 0.019). Paresthesia was found more frequently before surgery (p = 0.010) and at begin of rehabilitation (p = 0.006) in patients with paresis compared to patients without paresis. A statistically significant association was also evaluated between decreased lumbar mobility and laminectomy (p = 0.007). Patients with L5/S1 disc operation had a longer duration of radicular symptoms (p = 0.012), a decreased frequency of paresis (p = 0.040), but more often paresthesia (p = 0.001) compared with L4/5 operation.

T-lymphocyte subsets in occupationally exposed persons.

The percentage of CD2+, CD4+, CD8+ and HNK-1+ cells in peripheral blood was investigated in persons occupationally exposed to very low doses of ionizing radiation. Investigations were carried out by monoclonal antibodies and flow cytometry. While significant effects of age and smoking habits on the relative number of CD8 cells and CD4/CD8 ratios could be established, no influence of the very low radiation exposure on the profile of lymphocytic T cells in blood was found, except a very slight effect on the relative number of CD2+ cells.

Investigations on the use of EDTA-permeabilized E. coli cells in liquid suspension and animal-mediated genotoxicity assays.

The potential use of EDTA-permeabilized E. coli cells for the investigation of genotoxic effects of compounds with a large molecular configuration in vitro and in animal-mediated differential DNA-repair assays was studied. The indicator for the induction of (repairable) DNA damage was a pair of E. coli K-12 strains (343/765 and 343/753) differing vastly in DNA-repair capacity (uvr+/rec+ vs. uvrB/recA). Investigations on the influence of EDTA treatment on the viability of these strains show that during short-term exposure (3 min), the EDTA level should not exceed 0.5 mmole/l in the pretreatment mix, since at higher concentrations a marginal titer reduction of the repair-deficient strain occurs, thus indicating a weak genotoxic activity of this chelating agent. Comparisons of the results gained in vitro with permeabilized and untreated cells demonstrate that EDTA exposure leads to a substantial enhancement of the sensitivity of the indicator bacteria towards DNA damage induced by B(a)P and N-Ac-2AAF which is essential for the detection of genotoxic activities of these polycyclic aromatic compounds. Experiments to elucidate the possibility of employing EDTA-treated cells in vivo show that following intravenous and oral administration the recovery rates of permeabilized indicator strains from various mouse organs are substantially lower than those found under identical conditions (exposure time 150 min) with untreated strains. Nevertheless enough viable cells can be recovered from liver, spleen, kidneys, lungs and stomach to allow the investigation of organ-specific genotoxicity. It is furthermore noteworthy that exposure of permeabilized indicator cells in control animals (for 150 min) resulted in a marginal reduction of the relative survival of the repair-deficient strain in all organs investigated, whereas with non-treated strains such effects are only detectable after extended exposure periods. The observation of a slightly elevated genotoxic background under in vivo conditions does not prevent the assessment of the organ distribution of genotoxic effects induced by mutagens and/or carcinogens: in the case of B(a)P, intraperitoneal administration to mice in the dose range of 10-50 mg/kg body weight resulted in a pronounced dose-dependent inactivation of the uvrB/recA cells in the liver. Also in the lungs differential killing effects occurred at the highest dose tested, whereas no genotoxic activities were detectable in stomach, kidneys and spleen of the host animals.

[Local and systemic parameters in the synovial milieu]. / Lokale und systemische Parameter im synovialen Milieu.

Our own results as well as recent data from the literature confirm the already long known fact, that synovial fluid analysis allows only in very few diseases as for example a crystal synovitis a definite diagnosis in the individual case. In the majority of the patients this technique permits only to differentiate between inflammatory and non-inflammatory joint disease as well as an estimation of the local inflammatory activity of joint. The simultaneous histologic examination of synovial membrane according to our experience seems to bring no major additional information which exceeds the information given by each technique alone.

[Blood levels and therapeutic effectiveness of piroxicam as affected by the time of administration]. / Blutspiegelverlauf und therapeutische Wirksamkeit von Piroxicam in Abhängigkeit vom Zeitpunkt der Applikation.

The nonsteroidal antirheumatic preparation hydroxy-2-methyl-N-(2-pyridyl)-2H-1.2-benzothiazine-3-carboxamide 1,1-dioxide (piroxicam, Feldene) from the oxicam group is administered as a single dose of 20 mg/d. The question hence arose as to whether the therapeutic efficacy and the blood level curve (steady state) depend on the time of application. The investigation was carried out in 30 patients with arthroses of peripheral joints receiving the daily dose of piroxicam in the morning, at noon or in the evening. The results showed that irrespective of the time of administration the single dose of 20 mg/d led to a steady-state plasma level with the concentration required for efficacy. The result of therapy attained clinically also proved to be independent of the time of administration.

[Influence of acemetacin on DNA repair and DNA synthesis in vitro and in vivo (author's transl)]. / Untersuchungen über die Beeinflussung von DNS-Reparatur und DNS-Synthese durch Acemetacin in vitro und in vivo.

The effects of [1-(p-chlorobenzoyl)-5-methoxy-2-methyl-indole-3-acetoxy]-acetic acid (acemetacin, TV 1322, Rantudil) on DNA repair (unscheduled DNA synthesis) and semiconservative DNA synthesis have been investigated in vitro in mouse spleen cells and in vivo in human leukocytes. Quantitative determination of DNA repair was made possible by a computer program and additional measurement of parameters of uptake kinetics. in vitro results showed no influence on DNA synthesis and therapeutically relevant concentrations had no influence on DNA repair. 6 female patients with diagnosticized rheumatoid arthritis received acemetacin 4 x 30 mg daily for three months. During the duration of treatment there was no significant change in DNA repair capacity or in semiconservative DNA synthesis in comparison to pre-treatment values.