Association between urinary sodium and potassium excretion and blood pressure and inflammation in patients with rheumatoid arthritis

Hypertension is highly prevalent in patients with rheumatoid arthritis (RA). In other populations, high sodium (Na⁺) and low potassium (K⁺) intake are associated with an increased risk of hypertension, and in animal models, a high salt intake exacerbated arthritis. Patients with RA have many comorbidities associated with salt sensitivity, but their salt intake and its relationship to blood pressure and inflammation is unknown. Using the Kawasaki formula, Na⁺ and K⁺ urinary excretion (reflecting intake) was estimated in 166 patients with RA and 92 controls, frequency matched for age, sex, and race. Inflammatory markers and disease activity were measured in RA patients. We tested the associations between blood pressure and Na⁺ and K⁺ excretion. Estimated 24-h Na⁺ excretion was similarly high in both RA (median [IQR] 5.1 g, [3.9–6.6 g]) and controls (4.9 g, [4.0–6.5 g]), p?=?0.9, despite higher rates of hypertension in RA (54 vs. 39%, p?=?0.03). The Na⁺:K⁺ excretion ratio was significantly higher in RA (2.0 [1.6–2.4]) vs. 1.7 [1.5–2.1]), p?=?0.02] compared to controls. In RA, a lower K⁺ excretion was inversely correlated with diastolic blood pressure (adjusted β?=???1.79, p?=?0.04). There was no significant association between Na⁺ or K⁺ excretion and inflammatory markers. Despite a similar Na⁺ excretion, patients with RA had higher rates of hypertension than controls, a finding compatible with increased salt sensitivity. Patients with RA had a lower Na⁺:K⁺ excretion ratio than controls, and lower K⁺ excretion was associated with higher diastolic blood pressure in RA.     

Inflammation-associated insulin resistance: differential effects in rheumatoid arthritis and systemic lupus erythematosus define potential mechanisms

OBJECTIVE: Insulin resistance is increased by inflammation, but the mechanisms are unclear. The present study was undertaken to test the hypothesis that decreased insulin sensitivity is differentially associated with mediators of inflammation by studying 2 chronic inflammatory diseases of different pathogenesis, systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). METHODS: We measured fasting insulin, glucose, and lipid levels, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor alpha (TNFalpha), and coronary artery calcification in 103 patients with SLE and in 124 patients with RA. Insulin sensitivity was measured using the homeostasis model assessment (HOMA) index. RESULTS: The HOMA value was higher in RA patients (median 2.05 [interquartile range (IQR) 1.05-3.54]) than in SLE patients (1.40 [0.78-2.59]) (P = 0.007). CRP and ESR did not differ significantly in RA and SLE patients. Body mass index (BMI) was significantly correlated with the HOMA index in both RA (rho = 0.20) and SLE (rho = 0.54), independently of age, sex, race, and current use of corticosteroids. In RA patients, the HOMA index was also significantly positively correlated with IL-6 (rho = 0.63), TNFalpha (rho = 0.50), CRP (rho = 0.29), ESR (rho = 0.26), coronary calcification (rho = 0.26), and Disease Activity Score in 28 joints (rho = 0.21); associations adjusted for age, sex, race, BMI, and current use of corticosteroids remained significant (P < 0.05). In SLE patients, the HOMA index was also significantly correlated with ESR (rho = 0.35) and CRP (rho = 0.25), but not with other variables. The association between the ESR and the HOMA value in patients with SLE remained significant after adjustment for confounding covariates (P = 0.008). In multivariable models, the major contributing factors to the HOMA index were the BMI in SLE patients, and IL-6 and TNFalpha levels in RA patients. CONCLUSION: The pathogenesis of insulin resistance and its contribution to atherogenesis varies in different inflammatory settings.     

Prognosis of functional peripheral ischemias after partial body vibration

In 125 patients with acknowledged occupational damage due to vibration the results of oscillography of two consecutive expertises were compared at intervals of three years. On the one hand it could be shown that at younger age (less than 50 years) an improvement in functional peripheral circulatory disorders is possible, but on the other hand with increasing interval from the exposition to vibration a downward tendency to deterioration of acral circulatory disorders can be observed.     

Measurement of lung density by computed tomography.

Computed tomography scanners can be calibrated to provide reproducible measurements for a quantitative analysis of lung density. Typical histograms for inspiration and expiration are presented. The reproducibility of the method is demonstrated as well as the limitations caused by artifacts and incomplete inspiration. This method is suggested for follow-up studies of patients with diseases affecting the entire lung. Early detection of interstitial lung disorders also seems possible.     

Characterization of the mouse islet-specific glucose-6-phosphatase catalytic subunit-related protein gene promoter by in situ footprinting: correlation with fusion gene expression in the islet-derived betaTC-3 and hamster insulinoma tumor cell lines

Glucose-6-phosphatase (G6Pase) is a multicomponent system located in the endoplasmic reticulum comprising a catalytic subunit and transporters for glucose-6-phosphate, inorganic phosphate, and glucose. We have recently cloned a novel gene that encodes an islet-specific G6Pase catalytic subunit-related protein (IGRP) (Ebert et al., Diabetes 48:543-551, 1999). To begin to investigate the molecular basis for the islet-specific expression of the IGRP gene, a series of truncated IGRP-chloramphenicol acetyltransferase (CAT) fusion genes were transiently transfected into the islet-derived mouse betaTC-3 and hamster insulinoma tumor cell lines. In both cell lines, basal fusion gene expression decreased upon progressive deletion of the IGRP promoter sequence between -306 and -66, indicating that multiple promoter regions are required for maximal IGRP-CAT expression. The ligation-mediated polymerase chain reaction footprinting technique was then used to compare trans-acting factor binding to the IGRP promoter in situ in betaTC-3 cells, which express the endogenous IGRP gene, and adrenocortical Y1 cells, which do not. Multiple trans-acting factor binding sites were selectively identified in betaTC-3 cells that correlate with regions of the IGRP promoter identified as being required for basal IGRP-CAT fusion gene expression. The data suggest that hepatocyte nuclear factor 3 may be important for basal IGRP gene expression, as it is for glucagon, GLUT2, and Pdx-1 gene expression. In addition, binding sites for several trans-acting factors not previously associated with islet gene expression, as well as binding sites for potentially novel proteins, were identified.     

Vergleichende biomechanische Kompressionsversuche mit einem neuen Wirbelkörperersatzimplantat

The authors present a new titanium implant for replacement of the vertebral body (Synex). Possible indications would be fractures or dislocations with destruction of the anterior column, posttraumatic kyphosis as well as tumors in the throracolumbar spine. The construction has to be completed by a stabilizing implant. For best fit and contact to adjacent end-plates Synex is distractable in situ. The possibility of secondary dislocation or loss of correction should thereby be minimised. OBJECTIVES: We performed comparative compression tests with Synex and MOSS ("Harms mesh cage") on human cadaveric specimens of intact vertebrae (L1). The aim of the study was to measure the compressive strength of the vertebral body end-plate in uniaxial loading via both implants to exclude a caving of Synex in vivo. METHODS: 12 human cadaveric specimens of intact vertebrae (L1) were divided in 2 similar groups (matched pairs) according to bone mineral density (BMD), determined using DE-QCT. The specimens were loaded with axial compression force at a constant speed of 5 mm/min to failure and the displacement was recorded with a continuous load-displacement curve. RESULTS: The mean ultimate compression force (Fmax) showed a tendency towards a higher result testing Synex with 3396 N versus 2719 N (non significant). The displacement until Fmax was 2.9 mm in group S (Synex), which was half as long as in group M (5.8 mm). The difference was significant (p < 0.001). The compression force was twice as high and significantly (p < 0.05) higher with Synex at a displacement of 1 mm, 1.5 mm and 2 mm. A significant (p < 0.001) correlation (R = 0.89) between Fmax and BMD was found. CONCLUSIONS: Synex was found to be at least comparable to MOSS for suspensory replacement of the vertebral body at the thoracolumbar spine. A possible consequence of the significantly higher mean compression forces between 1 and 2 mm displacement might be a decreased segmental deformation or loss of correction.     

A novel, high-performance random array platform for quantitative gene expression profiling

We have developed a new microarray technology for quantitative gene-expression profiling on the basis of randomly assembled arrays of beads. Each bead carries a gene-specific probe sequence. There are multiple copies of each sequence-specific bead in an array, which contributes to measurement precision and reliability. We optimized the system for specific and sensitive analysis of mammalian RNA, and using RNA controls of defined concentration, obtained the following estimates of system performance: specificity of 1:250,000 in mammalian poly(A(+)) mRNA; limit of detection 0.13 pM; dynamic range 3.2 logs; and sufficient precision to detect 1.3-fold differences with 95% confidence within the dynamic range. Measurements of expression differences between human brain and liver were validated by concordance with quantitative real-time PCR (R(2) = 0.98 for log-transformed ratios, and slope of the best-fit line = 1.04, for 20 genes). Quantitative performance was further verified using a mouse B- and T-cell model system. We found published reports of B- or T-cell-specific expression for 42 of 59 genes that showed the greatest differential expression between B- and T-cells in our system. All of the literature observations were concordant with our results. Our experiments were carried out on a 96-array matrix system that requires only 100 ng of input RNA and uses standard microtiter plates to process samples in parallel. Our technology has advantages for analyzing multiple samples, is scalable to all known genes in a genome, and is flexible, allowing the use of standard or custom probes in an array.