Degradation of a chromogenic substrate by α2-macroglobulin from plasma of patients with rheumatoid arthritis

We have shown previously that serum from patients with rheumatoid arthritis (RA) contains a polyclonal B cell activator that is associated with α₂-macroglobulin (α₂M). Some biologic effects of this activator appear to be due to a trypsin-like protease attached to α₂M. Therefore, in the present study, we used an anti-α₂M antibody solid-phase assay, with Chromozym-Try as a substrate, to determine the level of α₂M-protease complexes in plasma α₂M. We found higher levels of these complexes in RA patients than in 2 control groups. Since α₂M-protease complexes have been shown to induce RA-like inflammation in experimental animals and to be produced by lymphoid cells, we speculate that they may be involved in the pathogenesis of RA. However, the role of the other cells or enzyme systems in the formation of these complexes has not yet been ruled out. Results of these investigations could lead to another link between activation of the immune system and joint inflammation.     

Twelve Weeks of Reversed Umbilical Flow in a Fetal Growth Restriction Case Associated with Severe Periconceptional Maternal Anemia

We present a case of a patient diagnosed with severe intrauterine growth restriction and periconceptional severe anemia, where the fetal well-being features, including reversal of umbilical artery end-diastolic flow and abnormal cerebroplacental ratio, remained stationary for 12 weeks. We are not aware of reports with similar findings, and the professionals should take into consideration the possibility of a “frozen” fetal well-being for a long time. Possibly, in our case, the evolution may be due to the prompt correction of the chronic severe maternal anemia. This approach may offer the opportunity to prolong the pregnancy, even in cases with apparently imminent delivery, as the association of reversal of umbilical artery end-diastolic flow.     

Full dynamics of a red blood cell in shear flow

At the cellular scale, blood fluidity and mass transport depend on the dynamics of red blood cells in blood flow, specifically on their deformation and orientation. These dynamics are governed by cellular rheological properties, such as internal viscosity and cytoskeleton elasticity. In diseases in which cell rheology is altered genetically or by parasitic invasion or by changes in the microenvironment, blood flow may be severely impaired. The nonlinear interplay between cell rheology and flow may generate complex dynamics, which remain largely unexplored experimentally. Under simple shear flow, only two motions, “tumbling” and “tank-treading,” have been described experimentally and relate to cell mechanics. Here, we elucidate the full dynamics of red blood cells in shear flow by coupling two videomicroscopy approaches providing multidirectional pictures of cells, and we analyze the mechanical origin of the observed dynamics. We show that contrary to common belief, when red blood cells flip into the flow, their orientation is determined by the shear rate. We discuss the “rolling” motion, similar to a rolling wheel. This motion, which permits the cells to avoid energetically costly deformations, is a true signature of the cytoskeleton elasticity. We highlight a hysteresis cycle and two transient dynamics driven by the shear rate: an intermittent regime during the “tank-treading-to-flipping” transition and a Frisbee-like “spinning” regime during the “rolling-to-tank-treading” transition. Finally, we reveal that the biconcave red cell shape is highly stable under moderate shear stresses, and we interpret this result in terms of stress-free shape and elastic buckling.     

Agreement of multislice CT angiography and MR angiography in assessing the degree of carotid artery stenosis in consideration of different methods of postprocessing

OBJECTIVE: We investigated the agreement of multislice computed tomography angiography (CTA) and magnetic resonance angiography (MRA) in the quantitative measurement of carotid artery stenosis. The dependency of the agreement of the chosen postprocessing procedures was also investigated. METHODS: Fifty consecutive symptomatic patients were included in this study. In all patients, a CTA was performed with a 16-slice CT scanner. Within 30 days, the extracranial vessels were examined using a combined time-of-flight and contrast-enhanced MRA. The CT data sets were used to calculate the degree of stenosis according to the North American Symptomatic Carotid Endarterectomy Trial, European Carotid Surgery Trial, and Common Carotid methods by means of the 1-mm thick, transverse raw data (RD), a sagittal maximum-intensity projection reconstruction, and sagittal multiplanar reconstruction. In addition, a semiautomated analysis was done using a specialized postprocessing software. For all combinations of postprocessing procedures and methods of calculating the degree of stenosis, the correlation coefficient and the agreement based on Bland/Altman plots were calculated. RESULTS: Eleven of the 100 primarily included carotid arteries could not be evaluated. The correlation coefficients for all combinations were comparable and lied in the interval between 0.932 and 0.787. The best correlation was found for the combination of RD/sagittal multiplanar reconstruction and ECST method. The evaluation of the agreement gave a systematic overestimation of CTA between 1.9% and 10.7% with a 95% confidence interval between +/-26.7% and +/-43.3%. With the semiautomated postprocessing software, additional 33 vessels could not be evaluated. The agreement of the calculated degrees of stenoses was worse than that of the planar procedures. CONCLUSIONS: CTA and MRA had a feasible agreement in measuring the degree of stenosis of the carotid arteries. The best result could be obtained for the evaluation of the RD and the NASCET method. In this case one has to take into account a systematic overestimation of CTA of 1.9%. The combination with an additional reconstructive postprocessing procedure did not improve the result but might be useful for the radiologist to identify the location of the closest narrowing.     

Chronic fatigue and indicators of long-term employment disability in psychosomatic inpatients

The major goal of this study was to determine indictors of long-term disability for psychosomatic inpatients with chronic fatigue syndrome. To this end, a cross-sectional study was performed with a random sample of patients (n=1000, response rate: 83.9%) at a psychosomatic inpatient clinic. 51.1% of the patients (n=429) reported intensely persistent exhaustion that had no logical relation to actual exertion. 159 (37.1%) patients in this group were disabled from working and these comprised the main target group of this study. Significantly more patients in the target group worked part time, were disabled for a disproportionately long period of time (50.9% of all were disabled for more than 6 months in the previous year), and felt stressed because of conflicts with their superiors and/or colleagues (in each case, P<0.01). While more frequent psychological comorbidity was not found, they reported physical complaints more often. It was not the patients fit for work who felt more burdened with chronic fatigue, but rather the employment-disabled, who were actually exposed to fewer demands. These patients had, in comparison with those fit to work, a stronger fixation on somatic complaints, inadequate perception of physical and psychic sensations, difficulties getting along with other people and in coping with a regular job (in each case, P<0.01). Prospective examination of these indicators could help detect predictor variables for long-term disability in chronic fatigue. Such predictors could contribute to timely social-medical assessment and treatment.     

Not left ventricular lead position,but the extent of immediate asynchrony reduction predicts long-term response to cardiac resynchronization therapy

Cardiac resynchronization therapy (CRT) is an effective treatment for a large subgroup of chronic heart failure patients. Various attempts to improve the high non-responder rate of 30 % by preoperative asynchrony assessment have failed. We hypothesized that superior response to CRT is correlated with greater acute reduction of asynchrony and that a concordant left ventricular (LV) lead is beneficial compared to a discordant lead. Hundred and eight consecutive CRT patients from our center were prospectively included. Clinical status and asynchrony parameters were assessed before, 1 day and 6 months after CRT implantation. Super-response was defined as an increase of the LV ejection fraction by ≥15 % and a decrease in LV end systolic volume (LVESV) by ≥30 %. When the criteria for super-response were not met, average response was given with a decrease of baseline LVESV ≥15 %. Sixty eight patients were classified as responders (63 %). Comparing super- (n = 19) and average (n = 49) responders, we found that greater acute reduction of LV asynchrony (change of asynchronous segments under CRT: ?1.3 vs. ?0.4, p < 0.05; decrease of LV intraventricular delay: ?34 ms vs. ?16 ms, p < 0.05) is associated with superior reverse remodeling after 6 months. Importantly, asynchrony parameters of super-, average and non-responders were almost identical at baseline. A concordant LV lead (n = 63) was not associated with improved LV reverse remodeling compared to a discordant lead (n = 28): LVEF: +8.6 % vs. +7.8 %, p = 0.91; LVESV: ?30.5 ml vs. ?23.8 mL, p = 0.84. A greater immediate reduction of LV asynchrony predicts superior response. Preoperative asynchrony parameters do not correlate with outcome. A concordant LV lead is not superior to a discordant lead.     

Impact of hip anatomical variations on the cartilage stress: A finite element analysis towards the biomechanical exploration of the factors that may explain primary hip arthritis in morphologically normal subjects

Background

Hip arthritis is a pathology linked to hip-cartilage degeneration. Although the etiology of this disease is not well defined, it is known that age is a determinant risk factor. However, hip arthritis in young patients could be largely promoted by biomechanical factors. The objective of this paper is to analyze the impact of some normal anatomical variations on the cartilage stress distributions numerically predicted at the hip joint during walking.

Methods

A three-dimensional finite element model of the femur and the pelvis with the most relevant axial components of muscle forces was used to simulate normal walking activity. The hip anatomical condition was defined by: neck shaft angle, femoral anteversion angle, and acetabular anteversion angle with a range of 110–130°, 0–20°, and 0–20°, respectively. The direct boundary method was used to simulate the hip contact.

Findings

The hydrostatic stress found at the cartilage and labrum showed that a ± 10° variation with respect to the reference brings significant differences between the anatomic models. Acetabular anteversion angle of 0° and femoral anteversion angle of 0° were the most affected anatomical conditions with values of hydrostatic stress in the cartilage near 5 MPa under compression.

Interpretation

Cartilage stresses and contact areas were equivalent to the results found in literature and the most critical anatomical regions in terms of tissue loads were in a good accordance with clinical evidence. Altogether, results showed that decreasing femoral or acetabular anteversion angles isolatedly causes a dramatic increase in cartilage loads.