Predictors of long-term survival in 5,680 patients admitted to a UK major trauma centre with thoracic injuries.

INTRODUCTION: The long-term outcomes of chest trauma are largely unknown. We sought to determine the predictors of in-hospital and long-term survival in patients admitted to a major trauma centre (MTC) with chest injuries and to evaluate spatial patterns of injury in our network area. METHODS: Retrospective analysis of data collected on the National Trauma Audit Research Network (TARN) database using multivariate analysis and Cox regression analysis. Spatial analysis was performed using ArcGis 10.7.1. RESULTS: Some 5,680 patients were admitted with chest trauma between December 1999 and December 2019. Median patient age was 45 years and the median Injury Severity Score (ISS) was 20. The proportion of patients who had an operation was 39.8%. Age, blood transfusion, head injury, shock, emergency thoracotomy and heart disease were predictors of hospital mortality (p < 0.05). However, having an operation on concomitant injuries was protective. ISS and Glasgow Coma Score were discriminators of in-hospital mortality (C-indices 0.76 and 0.80, respectively). The 10-year survival values for patients who survived to discharge from hospital and who were aged <40, 50, 60, 70, 80 and >80 years were 99%, 93%, 95%, 87%, 75% and 43%, respectively. Preadmission lung disease and alcohol/drug misuse were poor predictors of long-term survival (p < 0.05). Hotspot analysis revealed the areas with the highest incidents were all close to the MTC. CONCLUSIONS: The MTC is geographically central to areas with high numbers of trauma incidents. Although emergency thoracotomy was a predictor of poor in-hospital outcomes, having surgery for concomitant injuries improved outcomes. Patients surviving to discharge have good long-term survivals.

Common peroneal and posterior tibial ischemic nerve damage, a rare cause.

A 56-year old gentleman presented to our orthopaedic foot and ankle clinic, with unusual symptoms in his left foot. He described a tight sensation over his toes, "like sandpaper under his skin". The pain had started post operatively following a bilateral aorto-femoral bypass. He was subsequently investigated and found to have an ischemic lesion Identified in his common peroneal and posterior tibial nerve with associated muscle atrophy on EMG. This represents a previously unreported complication of aorto-femoral bypass surgery.

Microwave frequency sensor for detection of biological cells in microfluidic channels.

We present details of an apparatus for capacitive detection of biomaterials in microfluidic channels operating at microwave frequencies where dielectric effects due to interfacial polarization are minimal. A circuit model is presented, which can be used to adapt this detection system for use in other microfluidic applications and to identify ones where it would not be suitable. The detection system is based on a microwave coupled transmission line resonator integrated into an interferometer. At 1.5 GHz the system is capable of detecting changes in capacitance of 650 zF with a 50 Hz bandwidth. This system is well suited to the detection of biomaterials in a variety of suspending fluids, including phosphate-buffered saline. Applications involving both model particles (polystyrene microspheres) and living cells-baker's yeast (Saccharomyces cerevisiae) and Chinese hamster ovary cells-are presented.

Microfluidic electromanipulation with capacitive detection for the mechanical analysis of cells.

The mechanical behavior of cells offers insight into many aspects of their properties. We propose an approach to the mechanical analysis of cells that uses a combination of electromanipulation for stimulus and capacitance for sensing. To demonstrate this approach, polystyrene spheres and yeast cells flowing in a 25 mumx100 mum microfluidic channel were detected by a perpendicular pair of gold thin film electrodes in the channel, spaced 25 mum apart. The presence of cells was detected by capacitance changes between the gold electrodes. The capacitance sensor was a resonant coaxial radio frequency cavity (2.3 GHz) coupled to the electrodes. The presence of yeast cells (Saccharomyces cerevisiae) and polystyrene spheres resulted in capacitance changes of approximately 10 and 100 attoFarad (aF), respectively, with an achieved capacitance resolution of less than 2 aF in a 30 Hz bandwidth. The resolution is better than previously reported in the literature, and the capacitance changes are in agreement with values estimated by finite element simulations. Yeast cells were trapped using dielectrophoretic forces by applying a 3 V signal at 1 MHz between the electrodes. After trapping, the cells were displaced using amplitude and frequency modulated voltages to produce modulated dielectrophoretic forces. Repetitive displacement and relaxation of these cells was observed using both capacitance and video microscopy.

Defective excitation-contraction coupling in hearts of rats with congestive heart failure.

AIM: We examined the cellular basis for depressed cardiac contractility in rats with congestive heart failure (CHF) secondary to myocardial infarction. METHODS: Six weeks after ligation of the left coronary artery, CHF was confirmed by haemodynamic measures and echocardiographic demonstration of reduced myocardial contractility in vivo. Papillary muscles from CHF animals developed less force than those from sham operated (SHAM) animals. Cell shortening was measured in isolated ventricular myocytes voltage-clamped with high resistance electrodes. Ca2+ transients were measured in fluo-4 loaded myocytes. RESULTS: Contractions triggered by depolarizing test steps from a post conditioning potential of -70 mV were significantly smaller and had significantly reduced velocity of shortening in CHF compared with SHAM myocytes. However, contractions initiated from -40 mV, were similar in amplitude and velocity of shortening in CHF and SHAM cells. L-type Ca2+ current was not significantly different between CHF and SHAM cells, whether activated from -70 or -40 mV. Therefore, in SHAM cells, excitation-contraction coupling exhibited higher gain when contractions were initiated from negative (-70 mV), as compared with depolarized potentials (-40 mV). However, in CHF myocytes, excitation-contraction coupling gain was selectively depressed with steps from -70 mV. This depression of gain in CHF was not accompanied by a significant reduction in sarcoplasmic reticulum Ca2+ content. Isoproterenol increased Ca2+ transients less in CHF than SHAM myocytes. CONCLUSION: In this post-infarction model of CHF, the contractile deficit was voltage dependent and the gain of excitation-contraction coupling was selectively depressed for contractions initiated negative to -40 mV.

Monitoring of landfill leachate dispersion using reflectance spectroscopy and ground-penetrating radar.

The utility of ground-penetrating radar and reflectance spectroscopy in the monitoring of landfill sites has been investigated. Strong correlations between red edge inflection position and chlorophyll and heavy metal concentrations have been demonstrated from grassland species affected by leachate contamination of the soil adjacent to the landfill test site. This study demonstrated that reflectance spectroscopy can identify vegetation affected by leachate-contaminated soil at a range of spatial resolutions. To identify the vegetation affected by leachate contamination, the spectroradiometer must have contiguous bands at sufficient spectral resolution over the critical wave range that measures chlorophyll absorption and the red edge (between 650 and 750 nm). The utility of ground-penetrating radar data to identify leachate escaping from breakout points in the contaminant wall has also been demonstrated. An integrated approach using these techniques, combined with field and borehole sampling and contaminant migration modeling, offers a possible cost-effective monitoring approach for landfill sites.

Synergistic effect of particles and cyclic pressure on cytokine production in human monocyte/macrophages: proposed role in periprosthetic osteolysis.

Macrophages, activated by particulate wear debris, are important in the process of osteolysis, which occurs during joint implant loosening. We previously found increased levels of interleukin-1beta (IL-1beta), IL-6, and tumor necrosis factor-alpha in cultured macrophages subjected to cyclical pressure of 0.138 MPa, suggesting that cyclic pressure may be another relevant cause of macrophage activation. The current study first investigated the effects of a range of cyclic pressures on cultured macrophages, including an investigation of the time course of cytokine expression. At 0.138 MPa, supernatant levels of TNF-alpha were maximal at 12 h, whereas IL-6 and IL-1beta were maximal at 24 h. All four cyclic pressure levels tested (without particles) resulted in increased production of all three cytokines relative to control. These increases were most marked at 0.069 and 0.035 MPa, and the increase in cytokine production at 0.017 MPa was not statistically significant. Further studies demonstrated that conditioned media from cyclically pressurized macrophages stimulated bone resorption in a neonatal mouse calvarial assay system. There were increased levels of calcium released from calvaria cultured in conditioned media from pressurised monocytes, and an increase in tartate-resistant acid phosphatase-positive osteoclasts was observed microscopically. As particulate wear debris is important in implant loosening, ultra high molecular weight polyethylene particles were also added to the pressurized cell cultures. The experiments compared the effect of atmospheric pressure, cyclic pressure alone, particles alone, and particles and cyclic pressure combined. A combination of ultra high molecular weight polyethylene particles and cyclic pressure at 0.017 MPa resulted in a dramatic synergistic elevation of levels of all three cytokines compared with the levels found with either pressure or particles alone. We propose that monocyte/macrophage activation by cyclic pressure plays a major role in the osteolysis seen in aseptic loosening of implants. The synergistic effect observed between particles and pressure could accelerate implant loosening, and implies that reduction in either cyclic pressure (by improving implant fixation) or wear debris load would reduce osteolysis.

In contrast to forskolin and 3-isobutyl-1-methylxanthine, amrinone stimulates the cardiac voltage-sensitive release mechanism without increasing calcium-induced calcium release.

The objective of this study was to determine whether the voltage-sensitive release mechanism (VSRM) can be stimulated independently from Ca(2+)-induced Ca(2+) release (CICR) by drugs that elevate intracellular cAMP. Contractions were measured in voltage-clamped guinea pig ventricular myocytes at 37 degrees C. Na(+) current was blocked. We compared effects of agents that elevate cAMP through activation of adenylyl cyclase (1 microM forskolin), nonspecific inhibition of phosphodiesterases (PDEs) [100 microM 3-isobutyl-1-methylxanthine (IBMX)], and selective inhibition of PDE III (100-500 microM amrinone) on contractions initiated by the VSRM and CICR. Forskolin and IBMX significantly increased peak Ca(2+) current and CICR. In addition, these agents also markedly increased contractions elicited by test steps from -65 to -40 mV, which activate the VSRM. However, because these steps also induced inward current in the presence of forskolin or IBMX, CICR could not be excluded. In contrast, amrinone caused a large, concentration-dependent increase in VSRM contractions but had no effect on CICR contractions or Ca(2+) current. Sarcoplasmic reticulum Ca(2+), assessed by rapid application of caffeine (10 mM), was increased only modestly by all three drugs. Normalization of contractions to caffeine contractures indicated that amrinone increased fractional release by the VSRM, but not CICR. Forskolin and IBMX increased fractional release elicited by steps to -40 mV. Increases in CICR induced by forskolin and IBMX were proportional to caffeine contractures. Thus, positive inotropic effects of cAMP on VSRM contractions may be compartmentalized separately from effects on Ca(2+) current and CICR.

Cardiac excitation-contraction coupling: role of membrane potential in regulation of contraction.

The steps that couple depolarization of the cardiac cell membrane to initiation of contraction remain controversial. Depolarization triggers a rise in intracellular free Ca(2+) which activates contractile myofilaments. Most of this Ca(2+) is released from the sarcoplasmic reticulum (SR). Two fundamentally different mechanisms have been proposed for SR Ca(2+) release: Ca(2+)-induced Ca(2+) release (CICR) and a voltage-sensitive release mechanism (VSRM). Both mechanisms operate in the same cell and may contribute to contraction. CICR couples the release of SR Ca(2+) closely to the magnitude of the L-type Ca(2+) current. In contrast, the VSRM is graded by membrane potential rather than Ca(2+) current. The electrophysiological and pharmacological characteristics of the VSRM are strikingly different from CICR. Furthermore, the VSRM is strongly modulated by phosphorylation and provides a new regulatory mechanism for cardiac contraction. The VSRM is depressed in heart failure and may play an important role in contractile dysfunction. This review explores the operation and characteristics of the VSRM and CICR and discusses the impact of the VSRM on our understanding of cardiac excitation-contraction coupling.

Diverse lamb genotypes. 3. Eating quality and the relationship between its objective measurement and sensory assessment.

The effect of genotype on eating quality was evaluated on m. Longissimus thoracis et lumborum (LTL) muscle of 60 lambs. The lambs were sired by a selection of Texel (T), Poll Dorset (PD), Border Leicester (BL) and Merino (M) rams, crossed with Border Leicester x Merino (BLM) and Merino (M) ewes giving six genotypes (TxBLM, PDxBLM, TxM, PDxM, BLxM and MxM). The relationships between sensory panel assessment of eating quality attributes and pH, cooking loss and shear force were also investigated. No significant differences were observed between genotypes for panel assessment of tenderness, juiciness, aroma liking, aroma strength, flavour liking, overall acceptability and rating. MxM lambs had a significantly (P<0.05) higher flavour strength than BLxM lambs. pH was a poor indicator of any eating quality attributes, except aroma strength (r=0.3, P<0.05). Warner Bratzler shear force value (WB) and tenderness showed a significant (P<0.001) negative correlation (-0.7). Tenderness, flavour and juiciness were the most important sensory attributes, explaining 86.5% of the total variation in overall acceptability.

Regulation of a voltage-sensitive release mechanism by Ca(2+)-calmodulin-dependent kinase in cardiac myocytes.

A role for Ca(2+)-calmodulin-dependent kinase (CamK) in regulation of the voltage-sensitive release mechanism (VSRM) was investigated in guinea pig ventricular myocytes. Voltage clamp was used to separate the VSRM from Ca(2+)-induced Ca(2+) release (CICR). VSRM contractions and Ca(2+) transients were absent in cells dialyzed with standard pipette solution but present when 2-5 microM calmodulin was included. Effects of calmodulin were blocked by KN-62 (CamK inhibitor), but not H-89, a protein kinase A (PKA) inhibitor. Ca(2+) current and caffeine contractures were not affected by calmodulin. Transient-voltage relations were bell-shaped without calmodulin, but they were sigmoidal and typical of the VSRM with calmodulin. Contractions with calmodulin exhibited inactivation typical of the VSRM. These contractions were inhibited by rapid application of 200 microM of tetracaine, but not 100 microM of Cd(2+), whereas CICR was inhibited by Cd(2+) but not tetracaine. In undialyzed myocytes (high-resistance microelectrodes), KN-62 or H-89 each reduced amplitudes of VSRM contractions by approximately 50%, but together they decreased VSRM contractions by 93%. Thus VSRM is facilitated by CamK or PKA, and both pathways regulate the VSRM in undialyzed cells.

Losartan improves recovery of contraction and inhibits transient inward current in a cellular model of cardiac ischemia and reperfusion.

Losartan, a selective angiotensin II (AII) type I receptor antagonist, may protect against myocardial stunning and arrhythmia in ischemia and reperfusion. To examine the cellular basis for these protective actions, we studied effects of losartan and AII on contractile and electrical activity of ventricular myocytes exposed to simulated ischemia and reperfusion. Ionic currents were measured with voltage-clamp techniques and contractions were measured with a video edge detector. After 10 min of superfusion with Tyrode's solution at 37 degrees C, cells were exposed to simulated ischemia (hypoxia, acidosis, hyperkalemia, hypercapnia, lactate accumulation, and substrate deprivation) for 30 min followed by 25 min of reperfusion with normal Tyrode's solution. During ischemia, drug-treated cells were exposed to either 0.1 microM AII, 10 microM losartan, or both simultaneously. In reperfusion, contractions were depressed to 42% of preischemic levels in untreated cells. Losartan treatment significantly improved contractile recovery to 84% (P <. 05) of preischemic levels. AII-treated cells showed contractile recovery similar to untreated cells (40%), whereas cells treated with losartan plus AII recovered to 101% of preischemic levels. Cells exposed to losartan or losartan plus AII also exhibited reduced incidence of transient inward current (I(TI)) (20%, P <.05; 36%) relative to untreated cells (60%). However, I(TI) incidence was not altered by treatment with AII alone (57%). Treatment with exogenous agonist did not potentiate contractile depression or I(TI) incidence, and losartan exerted protective effects in the presence and absence of AII. Thus, losartan may have effects that are independent of AII receptor blockade.

The effect of cyclic pressure on human monocyte-derived macrophages in vitro.

Aseptic loosening and osteolysis around prosthetic joints are the principal causes of failure and consequent revision. During this process activated macrophages produce cytokines which are thought to promote osteolysis by osteoclasts. Changes in pressure within the space around implants have been proposed as a cause of loosening and osteolysis. We therefore studied the effect of two different regimes of cyclic pressure on the production of interleukin-1beta (IL-1beta), IL-6 and tumour necrosis factor-alpha (TNF-alpha) by cultured human monocyte-derived (M-D) macrophages. There was a wide variation in the expression of cytokines in non-stimulated M-D macrophages from different donors and therefore cells from the same donor were compared under control and pressurised conditions. Both regimes of cyclic pressure were found to increase expression of IL-6 and TNF-alpha. Expression of IL-1beta was increased by a higher-frequency regime only. Our findings suggest that M-D macrophages are activated by cyclic pressure. Further work will be required to understand the relative roles of frequency, amplitude and duration of applied pressure in the cellular effects of cyclic pressure in this system.

Regulation of contraction and relaxation by membrane potential in cardiac ventricular myocytes.

Control of contraction and relaxation by membrane potential was investigated in voltage-clamped guinea pig ventricular myocytes at 37 degrees C. Depolarization initiated phasic contractions, followed by sustained contractions that relaxed with repolarization. Corresponding Ca(2+) transients were observed with fura 2. Sustained responses were ryanodine sensitive and exhibited sigmoidal activation and deactivation relations, with half-maximal voltages near -46 mV, which is characteristic of the voltage-sensitive release mechanism (VSRM) for sarcoplasmic reticulum Ca(2+). Inactivation was not detected. Sustained responses were insensitive to inactivation or block of L-type Ca(2+) current (I(Ca-L)). The voltage dependence of sustained responses was not affected by changes in intracellular or extracellular Na(+) concentration. Furthermore, sustained responses were not inhibited by 2 mM Ni(2+). Thus it is improbable that I(Ca-L) or Na(+)/Ca(2+) exchange generated these sustained responses. However, rapid application of 200 microM tetracaine, which blocks the VSRM, strongly inhibited sustained contractions. Our study indicates that the VSRM includes both a phasic inactivating and a sustained noninactivating component. The sustained component contributes both to initiation and relaxation of contraction.

Increased expression of the gene for alpha-interferon-inducible protein in cardiomyopathic hamster heart.

Cardiomyopathic (CM) hamsters have a disruption in the delta-sarcoglycan gene which leads to progressive cardiac necrosis by 30 to 40 days of age, hypertrophy by 120 days, and heart failure by 250 days. We used differential display to detect other changes in mRNA levels in 30-, 60-, and 90-day-old wild-type and CM hamsters. We identified a 400-bp cDNA with sequence similarity to the human alpha-interferon-inducible protein (p27). This cDNA annealed with a 570-base mRNA whose steady-state levels were increased in 30-, 60-, and 90-day-old CM compared to wild-type heart. Increased expression of this hamster homolog of p27 (p27-h) was detected in CM hamster cardiac and skeletal muscle at 60 days of age but not in liver, kidney, or brain. Thus, an inherited defect in CM hamsters leads to increased expression of p27-h in advance of the development of hypertrophy and heart failure.

In and on: investigating the functional geometry of spatial prepositions.

Spatial prepositions such as in and on seem to denote semantically indeterminate spatial relations. This reflects, in part, the physical relationships between the objects in the scenes that they are used to portray. We argue that such physical relationships are best represented in terms of an inherently dynamic functional geometry which incorporates notions of location control. Two experiments are reported. They investigate the degree to which independent judgements of location control predict choice of description across a range of scenes. The results show that judgements of location control predict viewer's choice of description under certain circumstances. In the absence of prototypical geometric relations, control information has a strong influence on choice of description. However, when the scenes portray prototypical geometric relations, control information has less of an effect. The results support a hybrid account of the semantic representation underlying the prepositions with both a geometric and a functional component to it.

Role of voltage-sensitive release mechanism in depression of cardiac contraction in myopathic hamsters.

We investigated excitation-contraction (EC) coupling in isolated ventricular myocytes from prehypertrophic cardiomyopathic (CM) hamster hearts. Conventional and voltage-clamp recordings were made with high-resistance microelectrodes, and cell shortening was measured with a video-edge detector at 37 degrees C. Contractions were depressed in myocytes from CM hearts, whether they were initiated by action potentials or voltage-clamp steps. As in guinea pig and rat, contraction in hamster myocytes could be triggered by a voltage-sensitive release mechanism (VSRM) or Ca(2+)-induced Ca(2+) release (CICR). Selective activation of these mechanisms demonstrated that the defect in EC coupling was primarily caused by a defect in the VSRM. However, activation and inactivation properties of the VSRM were not altered. When the VSRM was inhibited, the remaining contractions induced by CICR exhibited identical bell-shaped contraction voltage relations in normal and CM myocytes. Inward Ca(2+) current was unchanged. Thus a defect in the VSRM component of EC coupling precedes the development of hypertrophy and failure in CM hamster heart.

Tetracaine can inhibit contractions initiated by a voltage-sensitive release mechanism in guinea-pig ventricular myocytes.

1. Effects of tetracaine on membrane currents and cell shortening were measured with high resistance electrodes, single-electrode voltage clamp (switch clamp) and a video edge detector at 37 C in cardiac ventricular myocytes. 2. Sequential voltage steps from -65 mV to -40 and 0 mV were used to activate two mechanisms of excitation-contraction (EC) coupling separately. The step to -40 mV activated the voltage-sensitive release mechanism (VSRM); the step to 0 mV1 activated Ca2+-induced Ca2+ release (CICR) coupled to inward Ca2+ current (IL). 3. Exposure to 100-300 microM tetracaine inhibited VSRM contractions but not CICR contractions. Inhibition of VSRM contractions was independent of INa blockade. In contrast, 100 microM Cd2+ blocked IL and CICR contractions, but not VSRM contractions. Simultaneous application of both agents blocked both mechanisms of EC coupling. 4. Contraction-voltage relationships were sigmoidal when the VSRM was available. However, when the VSRM was inhibited with 100-300 microM tetracaine, contraction-voltage relationships became bell-shaped. The tetracaine-insensitive contractions were abolished by 0.1 microM ryanodine, indicating that they were dependent on release of SR Ca2+. 5. At a higher concentration (1 mM) tetracaine also inhibited IL and contractions triggered by IL; however, the time course of effects on IL and associated contractions were different than for VSRM contractions. 6. With continuous application of tetracaine, the VSRM remained inhibited although SR Ca2+ stores increased 4-fold as assessed with caffeine. CICR contractions were not inhibited and maximum amplitude of contraction was not reduced. 7. Rapid application of tetracaine just before and during test steps also inhibited VSRM contractions, but without significantly affecting sarcoplasmic reticulum (SR) Ca2+ stores or CICR contractions. Maximum amplitude of contraction was reduced. 8. Rapid application of tetracaine (100-300 microM) allows preferential inhibition of the VSRM and provides a pharmacological method to assess the contribution of the VSRM to EC coupling.