Computational investigation of in situ chondrocyte deformation and actin cytoskeleton remodelling under physiological loading

Previous experimental studies have determined local strain fields for both healthy and degenerate cartilage tissue during mechanical loading. However, the biomechanical response of chondrocytes in situ, in particular the response of the actin cytoskeleton to physiological loading conditions, is poorly understood. In the current study a three-dimensional (3-D) representative volume element (RVE) for cartilage tissue is created, comprising a chondrocyte surrounded by a pericellular matrix and embedded in an extracellular matrix. A 3-D active modelling framework incorporating actin cytoskeleton remodelling and contractility is implemented to predict the biomechanical behaviour of chondrocytes. Physiological and abnormal strain fields, based on the experimental study of Wong and Sah (J. Orthop. Res. 2010; 28: 1554–1561), are applied to the RVE. Simulations demonstrate that the presence of a focal defect significantly affects cellular deformation, increases the stress experienced by the nucleus, and alters the distribution of the actin cytoskeleton. It is demonstrated that during dynamic loading cyclic tension reduction in the cytoplasm causes continuous dissociation of the actin cytoskeleton. In contrast, during static loading significant changes in cytoplasm tension are not predicted and hence the rate of dissociation of the actin cytoskeleton is reduced. It is demonstrated that chondrocyte behaviour is affected by the stiffness of the pericellular matrix, and also by the anisotropy of the extracellular matrix. The findings of the current study are of particular importance in understanding the biomechanics underlying experimental observations such as actin cytoskeleton dissociation during the dynamic loading of chondrocytes.     

Renal artery aneurysms: diagnosis and surveillance with 3D contrast-enhanced magnetic resonance angiography

The use of contrast-enhanced magnetic resonance angiography (CE-MRA) in screening for suspected renovascular disease may result in increased detection of renal artery aneurysms. We report the CE-MRA findings at diagnosis and follow-up in nine hypertensive patients with unsuspected renal artery aneurysms. A search of renal CE-MRAs of suspected renal artery stenosis at two tertiary referral institutions over 5 1/2 years was performed. All patients underwent CE-MRA using a fast spoiled gradient echo technique (TR/TE/flip 5.1–6 ms/1.6 ms/40°), scan matrix 512×196–224, 1 excitation, FOV 400–450 mm×266–360 mm, 32–50 mm×1.5–2 mm interpolated slices. Gadolinium-enhanced 3D images were obtained during breath holding. Images were evaluated and post-processed on a workstation by a single operator. Nine patients with renal artery aneurysms out of a total of 912 cases were found, all involving the main artery or divisions proximal to the renal hilum. Renal arteries distal to the hilum were not consistently visualized. The aneurysm was bilobed in one patient, multilocular in another and unilocular in all others. Severe stenosis of the renal artery proximal to the aneurysm was present in two. Four patients underwent follow-up showing no change in aneurysm size. CE-MRA reliably identifies aneurysms involving the main renal arteries and proximal branches. Once diagnosed, CE-MRA offers a safe, non-invasive modality for surveillance of aneurysm if active intervention is not planned.     

Effort thrombosis of the upper extremity in a young sportsman: Paget-Schroetter syndrome

Paget-Schroetter syndrome is the spontaneous thrombosis of the axillary/subclavian vein. A 16-year-old male presented with acute onset of right upper limb swelling after vigorous weight training. A venogram confirmed the diagnosis of Paget-Schroetter syndrome. He was started on intravenous thrombolytics followed by oral anticoagulation therapy. His symptoms resolved and he was symptom free at six-month follow-up. Thrombolytics and anticoagulation is the most widely accepted first-line therapy for this syndrome. Defining any anatomical anomaly as the predisposing factor in this condition is essential in the selection of which patients will benefit from thoracic outlet decompression.     

Chronic mitral regurgitation detected on cardiac MDCT: differentiation between functional and valvular aetiologies

Objective

To determine whether cardiac computed tomography (MDCT) can differentiate between functional and valvular aetiologies of chronic mitral regurgitation (MR) compared with echocardiography (TTE).

Methods

Twenty-seven patients with functional or valvular MR diagnosed by TTE and 19 controls prospectively underwent cardiac MDCT. The morphological appearance of the mitral valve (MV) leaflets, MV geometry, MV leaflet angle, left ventricular (LV) sphericity and global/regional wall motion were analysed. The coronary arteries were evaluated for obstructive atherosclerosis.

Results

All control and MR cases were correctly identified by MDCT. Significant differences were detected between valvular and control groups for anterior leaflet length (30?±?7 mm vs. 22?±?4 mm, P?<?0.02) and thickness (3.0?±?1 mm vs. 2.2?±?1 mm, P?<?0.01). High-grade coronary stenosis was detected in all patients with functional MR compared with no controls (P?<?0.001). Significant differences in those with/without MV prolapse were detected in MV tent area (?1.0?±?0.6 mm vs. 1.3?±?0.9 mm, P?<?0.0001) and MV tent height (?0.7?±?0.3 mm vs. 0.8?±?0.8 mm, P?<?0.0001). Posterior leaflet angle was significantly greater for functional MR (37.9?±?19.1° vs. 22.9?±?14°, P?<?0.018) and less for valvular MR (0.6?±?35.5° vs. 22.9?±?14°, P?<?0.017). Sensitivity, specificity, and positive and negative predictive values of MDCT were 100%, 95%, 96% and 100%.

Conclusion

Cardiac MDCT allows the differentiation between functional and valvular causes of MR.     

Quality of Surgery in Malawi: Comparison of Patient-Reported Outcomes After Hernia Surgery Between District and Central Hospitals

Background

District hospitals in Africa could meet the essential surgical needs of rural populations. However, evidence on outcomes is needed to justify investment in this option, given that surgery at district hospitals in some African countries is usually undertaken by non-physician clinicians.

Methods

Baseline and 2–3-month follow-up measurements were undertaken on 98 patients who had undergone hernia repairs at four district and two central hospitals in Malawi, using a modified quality-of-life tool.

Results

There was no significant difference in outcomes between district and central hospital cases, where a good outcome was defined as no more than one severe and three mild symptoms. Outcomes were marginally inferior at district hospitals (OR 0.79, 95% CI 0.63–1.0). However, in the 46 cases that underwent elective surgery at district hospitals, baseline scores for severe symptoms were worse (mean = 3.5) than in the 23 elective central hospital cases (mean = 2.5), p = 0.004. Also, the mean change (improvement) in symptom score was higher in district versus central hospital cases (3.9 vs. 2.3).

Conclusion

The study results support the case for investing in district hospital surgery in sub-Saharan Africa to increase access to essential surgical care for rural populations. This could free up specialists to undertake more complex and referred cases and reduce emergency presentations. It will require investments in training and resources for district hospitals and in supervision from higher levels.

     

P-selectin glycoprotein ligand 1 and beta2-integrins cooperate in the adhesion of leukocytes to von Willebrand factor

Von Willebrand factor (VWF) is an essential component of hemostasis. However, animal studies using VWF-deficient mice suggest that VWF may also contribute to inflammation. In the present study, we demonstrate that VWF was able to interact with polymorphonuclear leukocytes (PMNs) and monocytes under static and flow conditions. Adhesion under flow was dominated by short-lasting contact with resting PMNs, whereas adhesion of phorbol-12-myristate-13-acetate (PMA)-stimulated PMNs was characterized by firm adhesion. Transient binding of PMNs to VWF appeared to be mediated by P-selectin glycoprotein ligand-1 (PSGL-1). Moreover, recombinant PSGL-1 protein and cell surface-expressed PSGL-1 directly interacted with VWF. As for stable adhesion by PMA-stimulated PMNs, we observed that static adhesion and adhesion under flow were strongly inhibited (greater than 75%) by neutrophil-inhibitory factor, an inhibitor of beta2-integrin function. In addition, the isolated I-domain of alphaMbeta2 bound to VWF, and cell lines expressing alphaLbeta2 or alphaXbeta2 adhered efficiently to VWF. Taken together, our data showed that VWF can function as an adhesive surface for various leukocyte subsets (monocytes, PMNs). Analogous to VWF-platelet interaction, VWF provided binding sites for leukocyte receptors involved in rolling (PSGL-1) and stable (beta2-integrins) adhesion. VWF is unique in its intrinsic capacity to combine the rolling and the stable adhesion step in the interaction with leukocytes.     

Perineal burn care: French working group recommendations

Objectives

Burns to the perineum are frequently exposed to faeces. Diverting colostomy is often described to prevent faecal soiling. Because this technique is invasive with frequent complications, use of non-surgical devices including specifically designed faecal management systems has been reported in perineal burns.

Methods

In order to standardise the faecal management strategy in patients with perineal burns, a group of French experts was assembled. This group first evaluated the ongoing practice in France by analysing a questionnaire sent to every French burn centre. Based on the results of this study and on literature data, the experts proposed recommendations on the management of perineal burns in adults.

Results

Specifically designed faecal management systems are the first-line method to divert faeces in perineal burns. The working group proposed recommendations and an algorithm to assist in decisions in the management of perineal burns in four categories of patients, depending on total burn skin area, depth and extent of the perineal burn.

Conclusion

In France, non-surgical devices are the leading means of faecal diversion in perineal burns. The proposed algorithm may assist in decisions in the management of perineal burns. The expert group emphasises that large clinical studies are needed to better evaluate these devices.     

Potency and time course of mivacurium block during sevoflurane, isoflurane and intravenous anesthesia

PURPOSE: To determine the potency and time course of action of mivacurium neuromuscular block under routine clinical conditions during sevoflurane, isoflurane and intravenous anesthesia. METHOD: Patients were anesthetized with nitrous oxide 66% in oxygen and 1.5 MAC sevoflurane or isoflurane or a propofol infusion, neuromuscular block being monitored using mechanomyography. Potency was determined using administration of single doses of mivacurium of 40-100 micrograms.kg-1 and construction of dose-response curves (n = 72). The onset and duration of action were determined following a bolus dose of 0.2 mg.kg-1 of mivacurium (n = 30). RESULTS: The ED50 and ED95 (with 95% confidence limits) were estimated to be 42 (35-51) and 86 (74-98) micrograms.kg-1, 52 (45-60) and 89 (72-110) micrograms.kg-1, and 53 (45-62) and 95 (81-112) micrograms.kg-1 during sevoflurane, isoflurane and propofol anesthesia respectively (P < 0.05 between sevoflurane and propofol). Following administration of the 0.2 mg.kg-1 dose, neither the times (mean +/- SD) to maximum block (1.6 +/- 0.31, 1.7 +/- 0.21 and 1.6 +/- 0.45 min, respectively) nor the times to 25 and 90% recovery of T1 (20 +/- 4.5 and 33 +/- 8.8 min, 21 +/- 3.8 and 33 +/- 6.5 min, and 18 +/- 4.1 and 28 +/- 5.8 min respectively) were different among groups. The times to recovery of TOF ratio to 0.8 were 40 +/- 10.0, 36 +/- 8.5 and 29 +/- 5.5 min in the sevoflurane, isoflurane and propofol groups respectively (P = 0.017 between the sevoflurane and propofol groups). CONCLUSIONS: Under usual conditions of clinical anesthesia the potency of mivacurium was slightly enhanced during sevoflurane compared with intravenous anesthesia but the duration of action was only minimally prolonged during sevoflurane and isoflurane anesthesia.