Cytokines in rheumatoid arthritis: new therapeutic possibilities

The ingress of inflammatory leukocytes into the synovium is important for the pathogenesis of rheumatoid arthritis. Soluble inflammatory mediators regulate the inflammatory, chemotactic, adhesive, angiogenic events, as well as osteopenia associated with this disease. In this review authors discuss the role of a number of inflammatory mediators, such as cytokines, chemokines and growth factors in these processes. The outcome of arthritis is highly dependent on the imbalance between pro-inflammatory and anti-inflammatory mediators. Cytokine-related research also has important clinical relevance. Many of these proteins are detectable in the serum of rheumatoid patients and may eventually serve as useful laboratory markers of disease activity. Antirheumatic therapy currently used for the treatment of rheumatoid arthritis is often limited. Therefore, we need to consider alternative therapeutic regimens, such as the inhibition of cytokines and other soluble mediators, in order to prevent severe joint destruction. While there are many complex interactions involving cytokine networks and cascades in the arthritic joint, there are promising attempts to eliminate a single cytokine in clinical trials, such as ablation of tumor necrosis factor-alpha. Hopefully, the study of cytokines and their networks will lead to specific immunomodulatory therapies that will benefit rheumatoid patients by preventing joint destruction.     

Longitudinal bone mineral density changes in early rheumatoid arthritis

A prospective longitudinal study of patients with early RA was performed to examine the influence of disease duration, disease activity and physical activity on bone loss. Sixty-seven patients with non-steroid treated RA of less than 5 yr duration, including 16 patients with disease duration less than 6 months, had BMD measurements of the femoral neck and the lumbar spine over a 12-month period using dual energy X-ray absorptiometry. The BMD changes were compared with values from 72 control patients and were also correlated with serial measurements of disease activity (measured by the Stoke Index) and disability [measured by the Health Assessment Questionnaire (HAQ) score], at 3-monthly intervals over the 12-month period. No significant differences in BMD changes were found between RA patients and controls overall. Patients with disease duration of less than 6 months had significantly greater loss of BMD at the femoral neck (-3.9%, S.E.M. 1.5) than the remainder of the cohort (-0.2%, S.E.M. 0.7) (P = 0.02) and controls (-0.8%, S.E.M. 0.6). Lumbar spine BMD changes correlated with the initial Stoke Index (Rs-0.373, P = 0.01) but not mean Stoke Indices. There was no correlation of BMD changes with age or HAQ scores. These findings suggest that significant bone loss occurs within the first few months of disease in patients with RA.     

Is bone turnover a determinant of bone mass in rheumatoid arthritis?

OBJECTIVE: The aim of this study was to measure ultrasound (US) densitometric parameters [Broadband Ultrasound Attenuation (BUA), Speed of Sound (SOS), and stiffness of the os calcis] in patients with inflammatory bowel disease (IBD) and to compare the results with those obtained with conventional x-ray absorptiometry (DXA) of the lumbar spine. METHODS: Twenty-two patients with Crohn's disease (13 with ileal and nine with ileocolonic disease), 11 patients with ulcerative colitis (eight with left-sided and three with pancolitis), and 18 healthy controls. US densitometry of the right heel and DXA of the lumbar spine were performed within the same day. RESULTS: Compared to controls, IBD patients had significantly lower values with both methods, US and DXA. Forty-nine percent of patients had a lumbar T score below -1. Calcaneal SOS and stiffness of these patients were significantly reduced (p < 0.03 and p < 0.05, respectively). Positive significant correlations were found between lumbar DXA and calcaneal US parameters. Lumbar bone density and calcaneal US stiffness correlated inversely with the lifetime prednisone intake (p < 0.03 andp < 0.05, respectively), but not with age or duration of disease. A cut-off level of 80 dB/MHz for calcaneal BUA predicted axial osteopenia correctly in 74%, but some underestimation of spinal BMD was observed, especially in female patients with Crohn's disease. CONCLUSION: US evaluation of the os calcis gives results similar to those of conventional DXA and therefore may be used for screening IBD patients for axial osteoporosis. Because US does not expose patients to radiation, repeated measurements are possible and may be used to assess short term variations and the effect of treatment of IBD-associated bone disease.     

Helplessness and depression in rheumatoid arthritis.

Found that scores on a measure of helplessness mediated the relationship between severe, disabling rheumatoid arthritis (RA) and depression in 106 RA patients (aged 23–81 yrs). This association was independent of a previously demonstrated correlation between cognitive distortion and depression in RA patients. However, the association between disease severity and depression was mediated by Ss' views of their ability to control or cope with their disease. Both helplessness and cognitive distortion may be important factors in the development and treatment of depression among RA patients. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Changes in (markers of) bone metabolism during high dose corticosteroid pulse treatment in patients with rheumatoid arthritis

The aim of this study was to validate an incremental field test performed by wheelchair-dependent (WD) athletes. Nine male paraplegic subjects (mean age 28.9 +/- 4.2 years) performed an incremental field test (FT) and a comparable laboratory test (LT) with their own usual wheelchairs. Both tests started with an initial speed of 4 km.hr(-1) and increased by increments of 1 km.hr(-1) every minute until volitional exhaustion. The FT was an adapted Léger and Boucher test (ALBT) and was conducted on a 400 m tartan field marked-off every 50 m with pylons. Ventilatory data were collected every 15 s using a portable telemetric system (Cosmed K2, JFB International, Italy). The LT was performed on an adapted treadmill (Sopur, Germany) and ventilatory data were collected every minute using a breath-by-breath automated system (CPX, Medical Graphics, MN, USA). The LT and the FT were not significantly different for duration (8 min 50 +/- 1 min 24 vs 9 min 55 +/- 29 s), percentage of maximal heart rate (HR, 86.2 +/- 3.9 vs 89.7 +/- 5.3%), maximal minute ventilation (VE, 101.6 +/- 28.5 vs 96.8 +/- 28.2 1.min(-1)) and peak oxygen uptake (VO2 peak, 39.7 + 7.3 vs 36.1 + 5.8 ml.kg(-1).min(-1) assessed with the CPX and the K2, respectively. We concluded that the FT proposed in the present study is a valid test for direct VO2 peak assessment in wheelchair athletes using a portable VO2 telemetric system. Nonetheless, the Léger and Mercier model equation did not accurately predict VO2 max and further investigation is needed to determine a valid VO2 max prediction equation for these subjects during the FT.     

Fluoride therapy in prevention of rheumatoid arthritis induced bone loss

OBJECTIVE: To determine the efficacy of sodium fluoride (40 mg/day) in preventing rheumatoid arthritis (RA) induced bone loss, which may lead to osteoporosis. METHODS: We conducted an 18 month, randomized, double blind, placebo controlled trial in 38 patients with RA. The primary outcome measure was the difference in the percentage change between groups in lumbar spine bone mineral density (BMD) from baseline values after 18 months of therapy. The secondary outcome measures were the differences in the percentage change between groups in femoral neck, Ward's triangle, trochanter, and total body BMD from baseline after 18 months of therapy. RESULTS: There was a significant percentage difference (SD) between groups of 6.2% (7.3%) (p = 0.0005) in lumbar spine BMD after 18 months of treatment in favor of the fluoride group. The fluoride group experienced a 5.2% (8.4%) (p = 0.0125) increase, whereas the placebo group showed a 1.0% (4.8%) (p = 0.8015) decrease in lumbar spine BMD after treatment. No significant differences were found for the femoral neck, Ward's triangle, trochanter, and total body BMD in terms of the percentage changes from baseline within each treatment group or in the differences in the degree of change between groups after therapy. Lumbar spine BMD increased in about 80% of patients treated with fluoride (responders) compared to 44% of patients treated with placebo. CONCLUSION: The results showed that fluoride therapy was well tolerated and increased vertebral bone mass in patients with RA.     

Coping with rheumatoid arthritis.

Argues that despite the widespread assumption that psychological processes play an important role in rheumatoid arthritis (RA), and despite the recent intense activity in health psychology, RA has been ignored by psychological researchers. Questions concerning the extent and variability of dysfunction resulting from RA and the coping mechanisms that may mediate functional capacity are raised. The background literature to address these questions is reviewed, including information concerning diagnostic problems and approaches, adjustment to RA, and methodological problems in studies to date. It is suggested that the literature is clouded by diagnostic inconsistencies and neglect of the variety of areas of adjustment that may be affected by the disease, including employment and financial, physical (including pain), social, self-concept, and emotional. A project underway at the University of Saskatchewan, in which RA patients are being studied for coping behaviors that may contribute to their adaptation and functional capacity, is introduced as one means of addressing some of the outstanding issues in the area. (French abstract) (63 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Bovine bone grafting in occipito-cervical fusion for atlanto-axial instability in rheumatoid arthritis

Bovine bone chips (Surgibone) were used in occipito-cervical fusion in nine patients with atlanto-axial instability due to rheumatoid arthritis. The patients were examined with CT 12-15 months after surgery. Graft resorbtion was observed in one patient. The other 8 patients showed preserved grafts, in most cases the grafts appeared to be in contact with the underlying bone. One patient was revised, and at the grafted site a bony bridge was found. In conclusion, the use of bovine chips in posterior occipito-cervical fusion will not lead to predictable bone union. However, there seem to be exceptions to that rule.     

Backache--orthopedic diagnosis and special therapeutic possibilities

Back pain is a wide-spread complaint in modern society and in part an adverse effect resulting from present-day lifestyles. To date, too little attention has been drawn to efficient prevention. The treatment of patients affected with back pain today calls for an in-depth pathophysiological knowledge about the mechanism occurring on the spine. Diagnostic methods and non-operative treatment have been complemented specifically by chirotherapeutic methods. A systematic classification of the vertebragenous pain syndromes and the related treatment strategies have proven to be successful. Irrespectively of that, the individuality of diagnosis and the complaint's progress in each patient should be taken into account at all events. Cost-intensive diagnostic imaging should only be undertaken with a clear indication. Today, the overwhelming majority of back pain patients undergo a non-operative treatment. In case the conservative applications prove inefficient, it is possible to successfully operate on patients a with disc prolaps, degenerative instabilities as well as osseous spinal foraminal stenoses. A precondition is a precise causal diagnosis and a clear indication for operative intervention.     

Corticosteroid prescribing in rheumatoid arthritis and psoriatic arthritis

Embryos from certain mouse strains are arrested at the 2-cell stage in cell culture ('2-cell block'), whereas those from other strains develop to the blastocyst stage under the same conditions. It was previously shown that blocking embryos can be rescued in culture by aggregation with an excess of 2-cell stages of a non-blocking strain such as CBA x C57BL/6 F2. Here we have employed a LacZ transgene in a blocking strain (NMRI) to follow the fate of rescued blastomeres up to the blastocyst stage. We found that rescued blastomeres can participate in both inner cell mass and trophoblast formation, thus completely overcoming the 2-cell block.     

Pain coping strategies and depression in rheumatoid arthritis.

A study was conducted to examine the role of pain episodes and the role of active and passive pain coping strategies in depicting depression in 287 patients with rheumatoid arthritis (RA). The independent effects of pain and pain coping strategies, as well as the interaction effects between pain and pain coping strategies on depression, were evaluated cross-sectionally and prospectively over a 6-month interval. The cross-sectional findings revealed that pain, passive coping, and the interaction between pain and passive coping contributed independent variance, all accounting for higher depression. Of principal interest was the finding that the frequent use of passive pain coping strategies in the face of high pain contributed to the most severe level of depression over time. These results were obtained after controlling for the potentially confounding effects of prior depression, functional disability, and medication status. These data imply that there may be a potential benefit of developing techniques to reduce the use of passive pain coping strategies to deal with chronic arthritis pain in cognitive–behavioral pain management programs. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

New diagnostic and therapeutic possibilities in neonatal sepsis

Neonatal sepsis remains a major clinical problem in neonatology, with high morbidity and mortality rates. The host defence against infections is immature in the newborn infant, and this makes the child more susceptible to invasive infection. The neutrophil storage pool and various granulocyte functions are impaired. In addition, the levels of immunoglobulins and complement are low. The detection of raised levels of complement activation products and cytokines may be of diagnostic help at an early stage of neonatal infection. Rapid treatment with antibiotics is essential for a favourable outcome. Possible adjuvant treatment may be to reduce the relative immunodeficiency by giving immunoglobulins or colony-stimulating factors which increase the production of leukocytes. Further, the potent inflammatory reaction initiated by the microorganisms may be suppressed by various therapies. In spite of much research in this field, no such adjuvant treatment has so far been shown to improve the outcome of neonatal sepsis.     

Tumors in rheumatoid arthritis

Benign (bTu) and malignant tumours (mTu) were studied in a randomised autopsy material of 161 patients with rheumatoid arthritis (RA). The tissue specimens were fixed in 8% formaldehyde solution at pH 7.6 and embedded in paraffin. The tumours were diagnosed histologically and confirmed by immunohistochemical methods. Five benign (3.1%), and thirteen malignant tumours (8.1%) found observed in 18 (11.2%) of 161 cases. There was no significant difference between laboratory parameters of patients with malignant tumours and without tumours. One benign (0.62%) and seven malignant (4.35%) tumours led to death in 8 (4.97%) of 18 cases altogether. Neoplasms were detected clinically in 8 of 18 cases (44.4 rel%). None of tumorous patients received immunosuppressive treatment and only five had gold (Tauredon) therapy. Paraneoplastic syndromes with rheumatoid complaints may be excluded by the onset and duration of RA and tumours. Benign neurogenic tumours and malignant bronchioloalveolar carcinoma were frequently associated with RA not treated by immunosuppressive drugs. Our data do not support the assumption of a high risk of malignant lymphomas associated with RA treated with immunosuppressive therapy.