Interleukin-23 and its correlation with disease activity,joint damage,and functional disability in rheumatoid arthritis

The purpose of this study was to compare the serum interleukin (IL)-23 levels between rheumatoid arthritis (RA) patients and healthy controls and to determine the correlation of IL-23 levels with disease activity, joint damage and functional disability in RA. Serum samples were obtained from 45 patients with RA and 45 healthy controls. The enzyme-linked immunosorbent assay method was used for quantitative analysis of IL-23. All the RA patients were assessed for disease activity based on the 28-joint disease activity score, joint damage based on modified Sharp score, and functional ability using the Health Assessment Questionnaire–Disability Index. The mean serum IL-23 level was much higher among the RA patients (24.50 ± 13.98 pg/mL) compared to the controls (5.98 ± 3.40 pg/mL; p < 0.01). There was a significant positive relationship between IL-23 levels and disease activity and questionnaire scores (p = 0.003 and 0.020, respectively). On logistic regression analysis, IL-23 levels were significantly higher in patients with moderate to high disease activity (p = 0.008, odds ratio = 1.073, 95% confidence interval = 1.019–1.130) and patients with significant functional disability (p = 0.008, odds ratio = 1.085, 95% confidence interval = 1.021–1.153). RA patients have significantly higher levels of serum IL-23. The IL-23 levels correlate well with disease activity and functional disability but not with radiographic joint damage.     

Functional lengths of the lower limb arterial tree measured by CT angiography centreline analysis: implications for catheter lengths in peripheral angioplasty

Purpose

Lower limb angioplasty is a common procedure. However, arterial lengths have not been well studied and there is no evidence base for the optimum catheter lengths required for the various applications of femoral or distal below-the-knee angioplasty. The industry standard catheter measures 80 cm.

Method

Fifty CT angiograms were post-processed using vessel tracking and centreline analysis tools and lengths were measured from the ipsilateral first segment of the femoral artery (FSFA) (common femoral artery) to the contralateral FSFA and on to the second segment of the femoral artery (superficial femoral artery) and popliteal arteries down to the posterior tibial (PT) artery at the ankle. This allowed clinically meaningful lengths for ‘cross-over’ and ‘antegrade’ angioplasty to be calculated.

Results

Mean cross-over length to the second segment of the femoral artery as it crossed the femoral cortex was 72.3 cm, and the mean cross-over length to the popliteal artery at the knee joint was 83.8 cm, and the length from the FSFA to the PT was 85.1 cm.

Conclusion

Selection of a standard length catheter can result in a situation where the catheter is too short. Optimum catheter length for a particular task will reduce the need for catheter exchanges and use of multiple balloons and therefore reduce complications, procedure time, radiation dose and cost.     

Skin temperature of the hand in multiple system atrophy and Parkinson's disease

AimA previous study on a small number of patients showed that low skin temperature of the hands, the so called “cold hands sign”, may be useful for distinguishing multiple system atrophy (MSA) from Parkinson's disease (PD). We have further investigated skin temperature of the hand in a larger number of patients.MethodsSkin temperature on the palm was measured in 50 MSA (11 MSA-P and 39 MSA-C patients) and 50 PD patients, and 25 normal healthy subjects.ResultsPalm skin temperature was significantly lower in MSA patients (32.0 ± 2.7 °C) than in controls (34.1 ± 0.9 °C, p = 0.0002), but was not different compared with the PD group (32.9 ± 1.8 °C, p = 0.06). Temperatures of <28 °C were observed in 3 MSA patients (6%) and none of the PD patients and controls. There was no significant difference in palm skin temperature between patients with and without orthostatic hypotension for each patient group, or between MSA-P and MSA-C patients.ConclusionThe cold hand (<28 °C) is a useful marker for distinguishing MSA from PD, but it is not common in MSA patients, and its sensitivity may be low for differentiating between MSA and PD.     

Parabrachial nucleus involvement in multiple system atrophy

Multiple system atrophy (MSA) is associated with respiratory dysfunction, including sleep apnea, respiratory dysrhythmia, and laryngeal stridor. Neurons of the parabrachial nucleus (PBN) control respiratory rhythmogenesis and airway resistance. Objectives: The objective of this study is to determine whether there was involvement of putative respiratory regions of the PBN in MSA. Methods: We examined the pons at autopsy in 10 cases with neuropathologically confirmed MSA and 8 age-matched controls. Sections obtained throughout the pons were processed for calcitonin-gene related peptide (CGRP) and Nissl staining to identify the lateral crescent of the lateral PBN (LPB) and the Kölliker-Fuse nucleus (K-F), which are involved in respiratory control. Cell counts were performed using stereology. Results: There was loss of CGRP neurons in the PBN in MSA (total estimated cell counts for the external LPB cluster was 12,584 ± 1146 in controls and 5917 ± 389 in MSA, p < 0.0001); for the external medial PBN (MPB) cluster it was 15,081 ± 1758 in controls and 7842 ± 466 in MSA, p < 0.001. There was also neuronal loss in putative respiratory regions of the PBN, including the lateral crescent of the LPB (13,039 ± 1326 in controls and 4164 ± 872 in MSA, p < 0.0001); and K-F (5120 ± 495 in controls and 999 ± 308 in MSA, p < 0.0001). Conclusions: There is involvement of both CGRP and putative respiratory cell groups in the PBN in MSA. Whereas the clinical implications of CGRP cell loss are still undetermined, involvement of the LPB and K-F may contribute to respiratory dysfunction in this disorder.     

Substrate topography and size determine the fate of human embryonic stem cells to neuronal or glial lineage

Efficient derivation of neural cells from human embryonic stem cells (hESCs) remains an unmet need for the treatment of neurological disorders. The limiting factors for current methods include being labor-intensive, time-consuming and expensive. In this study, we hypothesize that the substrate topography, with optimal geometry and dimension, can modulate the neural fate of hESCs and enhance the efficiency of differentiation. A multi-architectural chip (MARC) containing fields of topographies varying in geometry and dimension was developed to facilitate high-throughput analysis of topography-induced neural differentiation in vitro. The hESCs were subjected to “direct differentiation”, in which small clumps of undifferentiated hESCs were cultured directly without going through the stage of embryoid body formation, on the MARC with N2 and B27 supplements for 7 days. The gene and protein expression analysis indicated that the anisotropic patterns like gratings promoted neuronal differentiation of hESCs while the isotropic patterns like pillars and wells promoted the glial differentiation of hESCs. This study showed that optimal combination of topography and biochemical cues could shorten the differentiation period and allowed derivation of neurons bearing longer neurites that were aligned along the grating axis. The MARC platform would enable high-throughput screening of topographical substrates that could maximize the efficiency of neuronal differentiation from pluripotent stem cells.