[Clinical characteristics and management of cervical necrotizing fasciitis].

Objective:To investigate the clinical characteristics and treatment of cervical necrotizing fasciitis. Method:Clinical data of 61 patients were analyzed retrospectively. All patients were underwent surgical debridement and treated with broad-spectrum antibiotics after diagnose. Result:Complications occurred in 14 patients. Fifty-nine patients were cured while 2 patients died. After 3 months or more follow-up, 3 patients accompanied with sequelae of vocal hoarseness, and no patient recurred or died. Conclusion:Early surgical debridement and the use of antibiotics should be taken as soon as possible after diagnosis of cervical necrotizing fasciitis, as well as control of comorbidities and systemic support treatment in order to prevent complications and deaths.

A power-law rheology-based finite element model for single cell deformation.

Physical forces can elicit complex time- and space-dependent deformations in living cells. These deformations at the subcellular level are difficult to measure but can be estimated using computational approaches such as finite element (FE) simulation. Existing FE models predominantly treat cells as spring-dashpot viscoelastic materials, while broad experimental data are now lending support to the power-law rheology (PLR) model. Here, we developed a large deformation FE model that incorporated PLR and experimentally verified this model by performing micropipette aspiration on fibroblasts under various mechanical loadings. With a single set of rheological properties, this model recapitulated the diverse micropipette aspiration data obtained using three protocols and with a range of micropipette sizes. More intriguingly, our analysis revealed that decreased pipette size leads to increased pressure gradient, potentially explaining our previous counterintuitive finding that decreased pipette size leads to increased incidence of cell blebbing and injury. Taken together, our work leads to more accurate rheological interpretation of micropipette aspiration experiments than previous models and suggests pressure gradient as a potential determinant of cell injury.

Mechanical responsiveness of the endothelial cell of Schlemm's canal: scope, variability and its potential role in controlling aqueous humour outflow.

Primary open-angle glaucoma is associated with elevated intraocular pressure, which in turn is believed to result from impaired outflow of aqueous humour. Aqueous humour outflow passes mainly through the trabecular meshwork (TM) and then through pores formed in the endothelium of Schlemm's canal (SC), which experiences a basal-to-apical pressure gradient. This gradient dramatically deforms the SC endothelial cell and potentially contributes to the formation of those pores. However, mechanical properties of the SC cell are poorly defined. Using optical magnetic twisting cytometry and traction force microscopy, here we characterize the mechanical properties of primary cultures of the human SC cell, and for the first time, the scope of their changes in response to pharmacological agents that are known to modulate outflow resistance. Lysophosphatidic acid, sphingosine-1-phosphate (S1P) and thrombin caused an increase in cell stiffness by up to 200 per cent, whereas in most cell strains, exposure to latrunculin A, isoproterenol, dibutryl cyclic-AMP or Y-27632 caused a decrease in cell stiffness by up to 80 per cent, highlighting that SC cells possess a remarkably wide contractile scope. Drug responses were variable across donors. S1P, for example, caused 200 per cent stiffening in one donor strain but only 20 per cent stiffening in another. Isoproterenol caused dose-dependent softening in three donor strains but little or no response in two others, a finding mirrored by changes in traction forces and consistent with the level of expression of ß(2)-adrenergic receptors. Despite donor variability, those drugs that typically increase outflow resistance systematically caused cell stiffness to increase, while in most cases, those drugs that typically decrease outflow resistance caused cell stiffness to decrease. These findings establish the endothelial cell of SC as a reactive but variable mechanical component of the aqueous humour outflow pathway. Although the mechanism and locus of increased outflow resistance remain unclear, these data suggest the SC endothelial cell to be a modulator of outflow resistance.

Biomechanical effects of environmental and engineered particles on human airway smooth muscle cells.

The past decade has seen significant increases in combustion-generated ambient particles, which contain a nanosized fraction (less than 100 nm), and even greater increases have occurred in engineered nanoparticles (NPs) propelled by the booming nanotechnology industry. Although inhalation of these particulates has become a public health concern, human health effects and mechanisms of action for NPs are not well understood. Focusing on the human airway smooth muscle cell, here we show that the cellular mechanical function is altered by particulate exposure in a manner that is dependent upon particle material, size and dose. We used Alamar Blue assay to measure cell viability and optical magnetic twisting cytometry to measure cell stiffness and agonist-induced contractility. The eight particle species fell into four categories, based on their respective effect on cell viability and on mechanical function. Cell viability was impaired and cell contractility was decreased by (i) zinc oxide (40-100 nm and less than 44 microm) and copper(II) oxide (less than 50 nm); cell contractility was decreased by (ii) fluorescent polystyrene spheres (40 nm), increased by (iii) welding fumes and unchanged by (iv) diesel exhaust particles, titanium dioxide (25 nm) and copper(II) oxide (less than 5 microm), although in none of these cases was cell viability impaired. Treatment with hydrogen peroxide up to 500 microM did not alter viability or cell mechanics, suggesting that the particle effects are unlikely to be mediated by particle-generated reactive oxygen species. Our results highlight the susceptibility of cellular mechanical function to particulate exposures and suggest that direct exposure of the airway smooth muscle cells to particulates may initiate or aggravate respiratory diseases.

Power-law rheology analysis of cells undergoing micropipette aspiration.

Accurate quantification of the mechanical properties of living cells requires the combined use of experimental techniques and theoretical models. In this paper, we investigate the viscoelastic response of suspended NIH 3T3 fibroblasts undergoing micropipette aspiration using power-law rheology model. As an important first step, we examine the pipette size effect on cell deformation and find that pipettes larger than ~7 µm are more suitable for bulk rheological measurements than smaller ones and the cell can be treated as effectively continuum. When the large pipettes are used to apply a constant pressure to a cell, the creep deformation is better fitted with the power-law rheology model than with the liquid drop or spring-dashpot models; magnetic twisting cytometry measurement on the rounded cell confirms the power-law behavior. This finding is further extended to suspended cells treated with drugs targeting their cytoskeleton. As such, our results suggest that the application of relatively large pipettes can provide more effective assessment of the bulk material properties as well as support application of power-law rheology to cells in suspension.

Universal behavior of the osmotically compressed cell and its analogy to the colloidal glass transition.

Mechanical robustness of the cell under different modes of stress and deformation is essential to its survival and function. Under tension, mechanical rigidity is provided by the cytoskeletal network; with increasing stress, this network stiffens, providing increased resistance to deformation. However, a cell must also resist compression, which will inevitably occur whenever cell volume is decreased during such biologically important processes as anhydrobiosis and apoptosis. Under compression, individual filaments can buckle, thereby reducing the stiffness and weakening the cytoskeletal network. However, the intracellular space is crowded with macromolecules and organelles that can resist compression. A simple picture describing their behavior is that of colloidal particles; colloids exhibit a sharp increase in viscosity with increasing volume fraction, ultimately undergoing a glass transition and becoming a solid. We investigate the consequences of these 2 competing effects and show that as a cell is compressed by hyperosmotic stress it becomes progressively more rigid. Although this stiffening behavior depends somewhat on cell type, starting conditions, molecular motors, and cytoskeletal contributions, its dependence on solid volume fraction is exponential in every instance. This universal behavior suggests that compression-induced weakening of the network is overwhelmed by crowding-induced stiffening of the cytoplasm. We also show that compression dramatically slows intracellular relaxation processes. The increase in stiffness, combined with the slowing of relaxation processes, is reminiscent of a glass transition of colloidal suspensions, but only when comprised of deformable particles. Our work provides a means to probe the physical nature of the cytoplasm under compression, and leads to results that are universal across cell type.

Single photon emission computerized tomography with capromab pendetide plus computerized tomography image set co-registration independently predicts biochemical failure.

PURPOSE: We evaluate the usefulness of pretreatment (111)Indium capromab pendetide (ProstaScint) planar imaging (immunoscintigraphy) plus single photon emission tomography co-registration with computerized tomography scans to detect occult metastatic disease and predict for biochemical failure, in a cohort of patients with a clinical diagnosis of localized adenocarcinoma of the prostate referred for primary radiotherapy. MATERIALS AND METHODS: Patients were followed after radiotherapy for evidence of biochemical failure using 2 criteria of prostate specific antigen clinical nadir +2 ng/ml and American Society for Therapeutic Radiology and Oncology Consensus definitions. Median followup was 58.8 months (mean 64.8). Clinical risk factors defined 3 risk groups of high (51), intermediate (72) and low (116). RESULTS: Overall biochemical failure was 18.3% vs 11.8% by the 2-BFC at 8-year actuarial analysis with 58.8 months median followup. By the CN +2 definition the control date for the cohort is 34.8 months. Pretreatment SPECT/CT suggested prostate cancer metastasis (22), seminal vesicle extension (20) and organ confined disease (197). Biochemical failure in patients having extra-periprostatic metastatic prostate cancer, seminal vesicle extension and organ confined disease uptake on SPECT/CT was 43.2%, 16.0% vs 14.7% (p = 0.0006); and 33.3%, 15.0% vs 8.7% (p = 0.0017) by the 2-BFC, respectively. Cox multiple regression analysis demonstrated that a finding of extra-periprostatic metastatic prostate on SPECT/CT significantly predicted a 4.2-fold greater risk (p = 0.0012) and a 4.5-fold greater risk (p = 0.0011) of failure by the 2-BFC than organ confined disease adjusting for treatment and risk group. CONCLUSIONS: Unconfirmed findings of extra-periprostatic metastatic prostate cancer on SPECT/CT immunoscintigraphy independently and significantly predicted an increased risk of biochemical failure in patients presenting for radiotherapy with a clinical diagnosis of localized prostate cancer.

Mechanical models for living cells--a review.

As physical entities, living cells possess structural and physical properties that enable them to withstand the physiological environment as well as mechanical stimuli occurring within and outside the body. Any deviation from these properties will not only undermine the physical integrity of the cells, but also their biological functions. As such, a quantitative study in single cell mechanics needs to be conducted. In this review, we will examine some mechanical models that have been developed to characterize mechanical responses of living cells when subjected to both transient and dynamic loads. The mechanical models include the cortical shell-liquid core (or liquid drop) models which are widely applied to suspended cells; the solid model which is generally used for adherent cells; the power-law structural damping model which is more suited for studying the dynamic behavior of adherent cells; and finally, the biphasic model which has been widely used to study musculoskeletal cell mechanics. Based upon these models, future attempts can be made to develop even more detailed and accurate mechanical models of living cells once these three factors are adequately addressed: structural heterogeneity, appropriate constitutive relations for each of the distinct subcellular regions and components, and active forces acting within the cell. More realistic mechanical models of living cells can further contribute towards the study of mechanotransduction in cells.