Rheumatoid cachexia in early rheumatoid arthritis: prevalence and associated variables.

OBJECTIVE: Rheumatoid cachexia (RC) is prevalent among patients with established rheumatoid arthritis (RA). Although changes in muscle mass and fat mass have been reported in early RA, these findings have not been classified according to existing RC definitions. This study aimed to describe the prevalence of RC and associated variables in patients with early RA. METHOD: This cross-sectional study included 87 patients. Body composition was evaluated with dual-energy X-ray absorptiometry after a median disease duration of 15 months. RC was defined as a fat-free mass index < 10th percentile and fat mass index > 25th percentile. We also assessed the erythrocyte sedimentation rate (ESR), C-reactive protein, Disease Activity Score in 28 joints, aerobic capacity, physical activity, traditional cardiovascular disease risk factors, functional disability, and sociodemographic data. Associations between RC and the independent variables were determined with logistic regression analyses. RESULTS: The prevalence of RC was 24%. RC was significantly associated [odds ratio (95% confidence interval)] with aerobic capacity [0.28 (0.09-0.89), p = 0.030], low-intensity physical activity [0.77 (0.60-0.99), p = 0.048], body mass index [0.78 (0.70-0.92), p = 0.002], waist circumference [0.96 (0.92-0.99), p = 0.023], body weight [0.94 (0.90-0.98), p = 0.004], and ESR at the time of diagnosis [1.02 (1.00-1.05), p = 0.033]. All of these associations remained significant after adjusting for age and gender. CONCLUSION: RC was highly prevalent in early RA. Patient outcome may be improved by detecting this condition early and applying treatments for improving inflammation, aerobic capacity, physical activity, and body composition.

Extent of atherosclerosis after 11-year prospective follow-up in patients with early rheumatoid arthritis was affected by disease severity at diagnosis.

Objective: Cardiovascular disease (CVD) is increased among patients with rheumatoid arthritis (RA). The underlying cause is not clear. In this prospective study, patients with early RA were investigated for associations between subclinical atherosclerosis and CVD risk factors as well as inflammation. Method: At diagnosis, RA patients were recruited into a prospective study. A subgroup was included (n = 55) for ultrasound measurements of intima-media thickness (IMT) at inclusion (T0), and after 5 years (T5) and 11 years (T11). Thirty-one age and gender-matched controls were also included for comparison. Results: IMT increased significantly between T0 and T11 among patients and controls (p < 0.0001). No statistically significant differences in IMT between patients and controls were detected at T11, T5, or T0 (p > 0.05 for all). In simple regression models, IMT at T11 was significantly associated with age (p < 0.0001), as well as systolic blood pressure at T0 (p < 0.01) and T11 (p < 0.01) among RA patients. Furthermore, the composite Systematic COronary Risk Evaluation (SCORE) measurements (p < 0.0001) and Reynolds risk score (p < 0.01) and the radiographic Larsen score (p < 0.05) at T0 were all significantly associated with IMT at T11. Results from conditional logistic regression analysis showed an increased progression rate between T0 and T11 in the RA group compared with controls (p < 0.05). Conclusion: We found increased atherosclerotic development among patients with RA compared with controls 11 years after diagnosis. The atherosclerotic burden was associated with disease severity at baseline.

Physical activity in rheumatoid arthritis: relationship to cardiovascular risk factors, subclinical atherosclerosis, and disease activity.

Objective: To investigate associations between physical activity and risk factors for cardiovascular disease (CVD), subclinical atherosclerosis, and disease activity in patients with early and long-standing rheumatoid arthritis (RA).Method: This cross-sectional study included 84 patients with early and 37 with long-standing RA (disease duration, mean ± sd: 1.4 ± 0.4 and 16.3 ± 2.3 years, respectively). Physical activity was measured using a combined accelerometer and heart-rate monitor. Further assessments were disease activity (erythrocyte sedimentation rate, Disease Activity Score in 28 joints), functional ability (Health Assessment Questionnaire), risk factors for CVD (blood lipids, i.e. triglycerides, high-density lipoprotein, low-density lipoprotein; blood glucose, blood pressure, sleeping heart rate, waist circumference, body mass index, and body fat), and subclinical atherosclerosis (pulse-wave velocity, augmentation index, and carotid intima-media thickness).Results: Physical activity variables did not differ between patients with early and long-standing RA. However, 37% of the patients with early and 43% of those with long-standing RA did not reach the World Health Organization's recommended levels of moderate to vigorous physical activity (MVPA). In a final multiple regression model, adjusted for age, gender, disease duration, and activity monitor wear time, higher total physical activity was associated with lower body fat and higher functional ability. With the same adjustments, more time spent in MVPA was associated with lower high-density lipoprotein and lower sleeping heart rate.Conclusions: Physical activity was associated with more favourable risk factors for CVD. However, many patients were physically inactive, stressing the importance of promoting physical activity in RA.

EULAR recommendations for cardiovascular disease risk management in patients with rheumatoid arthritis and other forms of inflammatory joint disorders: 2015/2016 update.

Patients with rheumatoid arthritis (RA) and other inflammatory joint disorders (IJD) have increased cardiovascular disease (CVD) risk compared with the general population. In 2009, the European League Against Rheumatism (EULAR) taskforce recommended screening, identification of CVD risk factors and CVD risk management largely based on expert opinion. In view of substantial new evidence, an update was conducted with the aim of producing CVD risk management recommendations for patients with IJD that now incorporates an increasing evidence base. A multidisciplinary steering committee (representing 13 European countries) comprised 26 members including patient representatives, rheumatologists, cardiologists, internists, epidemiologists, a health professional and fellows. Systematic literature searches were performed and evidence was categorised according to standard guidelines. The evidence was discussed and summarised by the experts in the course of a consensus finding and voting process. Three overarching principles were defined. First, there is a higher risk for CVD in patients with RA, and this may also apply to ankylosing spondylitis and psoriatic arthritis. Second, the rheumatologist is responsible for CVD risk management in patients with IJD. Third, the use of non-steroidal anti-inflammatory drugs and corticosteroids should be in accordance with treatment-specific recommendations from EULAR and Assessment of Spondyloarthritis International Society. Ten recommendations were defined, of which one is new and six were changed compared with the 2009 recommendations. Each designated an appropriate evidence support level. The present update extends on the evidence that CVD risk in the whole spectrum of IJD is increased. This underscores the need for CVD risk management in these patients. These recommendations are defined to provide assistance in CVD risk management in IJD, based on expert opinion and scientific evidence.

Responsiveness of platelets during storage studied with flow cytometry--formation of platelet subpopulations and LAMP-1 as new markers for the platelet storage lesion.

BACKGROUND AND OBJECTIVES: Storage lesions may prevent transfused platelets to respond to agonists and arrest bleeding. The aim of this study was to evaluate and quantify the capacity of platelet activation during storage using flow cytometry and new markers of platelet activation. MATERIALS AND METHODS: Activation responses of platelets prepared by apheresis were measured on days 1, 5, 7 and 12. In addition, comparisons were made for platelet concentrates stored until swirling was affected. Lysosome-associated membrane protein-1 (LAMP-1), P-selectin and phosphatidylserine (PS) exposure were assessed by flow cytometry on platelets in different subpopulations in resting state or following stimulation with platelet agonists (cross-linked collagen-related peptide (CRP-XL), PAR1- and PAR4-activating peptides). RESULTS: The ability to form subpopulations upon activation was significantly decreased already at day 5 for some agonist combinations. The agonist-induced exposure of PS and LAMP-1 also gradually decreased with time. Spontaneous exposure of P-selectin and PS increased with time, while spontaneous LAMP-1 exposure was unchanged. In addition, agonist-induced LAMP-1 expression clearly discriminated platelet concentrates with reduced swirling from those with retained swirling. This suggests that LAMP-1 could be a good marker to capture changes in activation capacity in stored platelets. CONCLUSION: The platelet activation potential seen as LAMP-1 exposure and fragmentation into platelet subpopulations is potential sensitive markers for the platelet storage lesion.

Circulating plasma levels of cathepsin S and L are not associated with disease severity in patients with rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) is characterized by chronic synovitis and articular cartilage destruction. Increased activities of cathepsin S and cathepsin L, two potent cysteine proteases, are thought to play a role in the pathogenesis of the irreversible articular cartilage destruction. Nevertheless, data regarding the potential importance of the cathepsins as circulating biomarkers in RA patients are limited. METHOD: Subjects enrolled in this study are part of a larger study where patients from the three northern counties of Sweden diagnosed with early RA are followed in an ongoing prospective study. In total, 71 patients were included, along with 44 age- and sex-matched control subjects. Plasma levels of cathepsin S and L were analysed. Disease severity was assessed using the 28-joint count Disease Activity Score (DAS28). RESULTS: Plasma levels of cathepsin S and L were significantly increased in patients with RA compared to healthy controls (p < 0.05 for both). However, in the patients with RA, no association between the cathepsins and the severity of the disease, as characterized by DAS28, was observed (p > 0.51). CONCLUSIONS: Although circulating levels of cathepsin S and L were significantly increased in patients with recently diagnosed RA, our data do not support the notion that circulating levels of cathepsins are relevant biomarkers for disease severity.

Absolute intensities of NH-stretching transitions in dimethylamine and pyrrole.

Vibrational spectra of vapor-phase dimethylamine (DMA) and pyrrole have been recorded in the 1000 to 13000 cm(-1) region using long path conventional spectroscopy techniques. We have focused on the absolute intensities of the NH-stretching fundamental and overtone transitions; Δν(NH) = 1-4 regions for DMA and the Δν(NH) = 1-3 regions for pyrrole. In the Δν(NH) = 1-3 regions for DMA, evidence of tunneling splitting associated with the NH-wagging mode is observed. For DMA, the fundamental NH-stretching transition intensity is weaker than the first NH-stretching overtone. Also, the fundamental NH-stretching transition in DMA is much weaker than the fundamental transition in pyrrole. We have used an anharmonic oscillator local mode model with ab initio calculated local mode parameters and dipole moment functions at the CCSD(T)/aug-cc-pVTZ level to calculate the NH-stretching intensities and explain this intensity anomaly in DMA.

Overtone spectra of 2-mercaptoethanol and 1,2-ethanedithiol.

Vibrational spectra of vapor-phase 1,2-ethanedithiol and 2-mercaptoethanol were recorded to investigate weak intramolecular interactions. The spectra were recorded with conventional absorption spectroscopy and laser photoacoustic spectroscopy in the 2000-11,000 cm(-1) region. The room temperature spectra of each molecule are complicated by contributions from several conformers. Anharmonic oscillator local-mode calculations of the OH- and SH-stretching transitions have been performed to facilitate assignment of the different conformers in the spectra. We observe evidence of hydrogen-bond-like interactions from OH to S, but not from SH to O or S. The OH to S intramolecular interaction in 2-mercaptoethanol is weak and comparable to that found in the OH to O interaction in ethylene glycol.

Atherothrombotic events in rheumatoid arthritis are predicted by homocysteine - a six-year follow-up study.

OBJECTIVE: The aim of this study was to investigate whether homocysteine is linked to atherothrombotic (AT) events in patients with rheumatoid arthritis (RA). METHODS: Analysis of homocysteine (Hcy) levels was carried out in 235 consecutive RA patients. They were followed-up for 6.5 years or until death, with analysis of AT risk factors and the type and length of DMARD and corticosteroid treatment. The disease history before inclusion was collected. Six categories of AT events were defined. In addition, the diagnosis of the patients at follow-up was co-analyzed with the nationwide population-based Swedish Inpatient Register and Death Register to certify all events. RESULTS: The Hcy level was found to be higher in males (p<0.05) and increased with age (p<0.001). Patients with folic acid supplementation had significantly lower levels, while those on corticosteroids had higher levels. High Hcy levels predicted AT events (n=48) during a 6.5-year follow-up adjusted for age and male sex in a logistic regression analysis. CONCLUSION: In this study, RA patients on folic acid had lower Hcy levels. High Hcy levels (in addition to age, sex and diabetes) predicted AT event prospectively.

Increased incidence of stroke and impaired prognosis after stroke among patients with seropositive rheumatoid arthritis.

OBJECTIVE: To examine the incidence of, and outcome after, a stroke in patients with rheumatoid arthritis (RA) compared with the general population. METHODS: The northern Sweden MONICA register was used to compare the incidence of stroke in a cohort of RA patients with the general population. Forty RA patients who had also suffered a stroke were identified. For each patient with RA, three controls with a history of stroke but without RA were randomly collected from the same register, and matched for age and sex. RESULTS: The standardised incidence ratio (SIR) for stroke was 2.7 in RA patients compared with the general population (p<0.05). During the follow-up, RA patients had a higher overall case fatality (CF) following stroke compared with controls (hazard ratio (HR) =1.70, p<0.05). CONCLUSIONS: Both the incidence of a stroke, and the subsequent CF, were higher among RA patients compared with the general population. The results emphasize the necessity of optimising the prevention of stroke and follow-up care after a stroke in RA.

Vibrational overtone spectroscopy of three-membered rings.

We have recorded vapor-phase photoacoustic spectra of cyclopropane, ethylene oxide, and ethylene sulfide in the third, fourth, and fifth CH-stretching overtone regions. We have used a harmonically coupled anharmonic oscillator local mode model to facilitate analysis of the spectra. Fermi resonance between the CH-stretching and HCH-bending vibrations is essential to explain the observed wide and multistructured CH-stretching overtone bands. A number of weak combination bands can account for the remaining experimental features observed to the blue of the CH-stretching regions. We have reassigned the fundamental spectra of these three-membered rings.

Accumulation of persistent organic pollutants in Tasmanian platypus (Ornithorhynchus anatinus).

Tailfat samples were collected from 56 platypuses, 38 male and 18 female in Tasmania. No statistically significant, nor apparent, differences between the sexes were found for tailfat lipid levels and DDT and its metabolites. Lindane and PCB concentrations in tailfat lipid. Apparently--but not statistically--significantly different levels of DDT and its metabolites. Lindane and PCB concentrations were found in animals from different geographic regions of the State. Higher concentrations of DDT and its metabolites and Lindane were related to the intensity of agricultural activity and elevated PCB levels were mainly found in animals from zones with industrial and hydroelectric developments.

Use of semi-permeable membrane devices to monitor pollutants in water and assess their effects: a laboratory test and field verification.

Uptake of eight pesticides of different classes (organochlorines, synthetic pyrethroids, dinitroanilines, amides) by semi-permeable membrane devices (SPMDs) was studied in a laboratory continuous-flow system. After 20 days of exposure, membrane concentration factors were in the range of 50 000-120 000 for all the analytes except for the amide herbicides propachlor and alachlor, which were not detected in any of the SPMDs. The kinetic data and mathematical models were used to calculate analyte uptake rate constants, SPMD lipid/water partition coefficients, average sampling rates and concentrations of the pesticides in water. To assess the effects of concentrated pesticides, standard bioassays (Salmonella/histidine reversion assay and bioluminescence inhibition in Vibrio fischeri test) were incorporated in the SPMD technique. To test the method in an environmental situation, SPMDs were deployed in polluted sites in Lithuania. Polynuclear aromatic hydrocarbons were the major pollutants detected in the SPMDs deployed in the field. All the SPMD dialysates were highly toxic in the bioluminescence inhibition test but no mutagenic activity was observed in the Salmonella/histidine reversion assay.

Uptake of organochlorine pesticides by solvent-filled cellulose and polyethylene membranes.

Membrane-based passive samplers were used to study the uptake of organochlorine pesticides (lindane, aldrin, dieldrin, and chlorpyriphos) in a continuous-flow system. The membranes were filled with cyclohexane and a mixture of cyclohexane and triolein. Uptake of the chemicals was 24-84 times faster in polyethylene membranes compared to that in cellulose membranes. This is a clear indication that polar cellulose membrane hinders the transport of lipophilic compounds. Though uptake rates in polyethylene membranes were much higher, they were unable to retain the receiving solvent for longer time periods. The diffusion rate of chemicals through polyethylene membranes was dependent not only on their lipophilicity but their molecular mass as well.

Monitoring of persistent, lipophilic pollutants in water and sediment by solvent-filled dialysis membranes.

Dialysis membranes filled with solvents can be used to monitor persistent, lipophilic pollutants in marine and fresh water environments, to predict levels of bioavailable compounds in organisms, and to study bioaccumulation mechanisms. The membranes are filled with n-hexane and exposed for 1 to several weeks in the water or in the sediment. The solvent impregnates the membrane, makes it unsuitable for periphyton growth, and prevents bacterial degradation. The membranes can also be used in environments too polluted for biological indicators to survive. The use of membranes with a molecular weight cutoff of 1000 Da prevents substances of higher molecular weight from diffusing through their walls, thereby simplifying the cleanup procedure. Internal standards in the solvent can be quantified to ensure that the membrane functions properly during the exposure. Uptake and depuration of organochlorine residues by the membranes seem to be governed by equilibrium partitioning.

Suppression of endocytosis in polyclonally activated Con A-stimulated T lymphocytes by 25-hydroxycholesterol.

Endocytosis in polyclonally activated, Con A-stimulated spleen cell cultures was analyzed. It was found that as lymphocytes differentiate to acquire cytotoxic capability their endocytic activity also increases, reaching a plateau at 48 hr. Inhibition of sterol synthesis reduced endocytic rates by as much as 50% when 25-hydroxycholesterol was added during the first 24 hr of culture, the time at which sterol synthesis is at its maximum. When 25-hydroxycholesterol was added after the cycle of sterol synthesis, little or no suppression of endocytosis was seen. Compactin, which is an allosteric, competitive inhibitor of HMG-CoA reductase (the rate-limiting enzyme in the sterol biosynthetic pathway), produced a similar abrogation of endocytic rate. The effect of inhibition of sterol synthesis on endocytosis can be counteracted by the addition of cholesterol to the cultures. It is hypothesized that the dynamic process of endocytosis plays a role in the reorganization of membrane components necessary for the expression of the differentiated state of cytotoxicity.