Chest X-rays in COPD screening: are they worthwhile?

The BTS/NICE COPD guideline recommends a chest X-ray at initial COPD evaluation; this is a grade D recommendation based on expert opinion. We have investigated which pathologies other than COPD are detected by chest X-ray and how they alter management. Dundee smokers aged 40 or over and receiving bronchodilators are assessed for COPD by their practice nurse and offered a chest X-ray if there is no record of a chest X-ray within the previous three years. We retrospectively analysed the chest X-ray reports and case records of these patients. The chest X-ray report was structured with 7 specific questions, most importantly "Are there any features of other disease likely to be causing dyspnoea?" and "Are there any features to suggest lung cancer?" Management of patients with chest X-ray findings suggesting other disease causing dyspnoea or lung cancer was assessed by questionnaire and case record study. Five hundred forty-six consecutive chest X-ray reports were analysed. Fourteen percent of all chest X-rays detected potentially treatable dyspnoea causing disease; where management following receipt of X-ray reports was audited, 84% were thought to help. Eleven lung cancers were detected, 3 had stage 1 disease. Considerable benign and malignant pathology is detected by chest X-ray performed at initial COPD assessment. Clinical management is changed in the majority with a potentially treatable abnormality. This evidence suggests that the NICE guideline to perform chest X-ray at initial COPD evaluation should be elevated from a grade D to grade C recommendation.

Chronic hepatitis C infection and sex hormone levels: effect of disease severity and recombinant interferon-alpha therapy.

BACKGROUND: We aimed to investigate the associations between androgen status and markers of liver disease severity and to determine the effect of interferon-alpha (IFN-alpha) treatment on sex hormone levels in the context of hepatitis C infection. METHODS: We audited liver biopsy and sex hormone data from 35 men with chronic hepatitis C and a separate group of 11 men with hepatitis C who received IFN-alpha treatment at Fremantle Hospital. RESULTS: We found that men with low fibrosis scores (0-2) on the modified Knodell histological activity index were more likely to have lower sex hormone-binding globulin (SHBG) levels (38.2 +/- 13.2 vs 66.6 +/- 43.3 nmol/L, P < 0.001) and higher free testosterone levels (380.4 +/- 102.0 vs 255.9 +/-83.0 pmol/L, P = 0.01) than those with higher fibrosis scores (3-6). SHBG directly correlated with fibrosis scores (r = 0.37, P = 0.032). Free testosterone levels inversely correlated with liver fibrosis scores (r = -0.43, P = 0.011). A transient reduction in total testosterone of 5.7 +/- 4.2 nmol/L (P = 0.014) occurred within the first 6 months of IFN-alpha therapy although free testosterone was unaffected. CONCLUSION: More severe liver disease was associated with lower free testosterone and higher SHBG. IFN-alpha therapy reduced total testosterone but not to hypogonadal levels, with no decline in free testosterone. These data suggest that liver disease in hepatitis C infection modulates androgen status indirectly via increased SHBG. Screening for androgen deficiency in the context of hepatitis C infection should selectively target men with more severe liver disease or documented higher grade fibrosis.

Red blood cells from the South American rattlesnake (Crotalus durissus terrificus) regulate volume incompletely following osmotic shrinkage and swelling in vitro.

The ability of rattlesnake (Crotalus durissus terrificus) red blood cells to volume regulate in vitro has been investigated. Blood was drawn through a catheter inserted in the dorsal aorta and equilibrated to gas mixtures of different composition. Cells shrunken osmotically by increasing the extracellular osmolarity from approximately 291 mosm l(-1) (n=3) to approximately 632 mosm l(-1) (calculated) only partially regulated their volume back towards the original volume either at pH 7.51+/-0.05 (mean+/-S.D., n=5) or pH 7. 20+/-0.06 (mean+/-S.D., n=3). There was no improvement of the regulatory volume increase at low haemoglobin oxygen saturation. The limited volume restoration was inhibited by separate additions of amiloride (10(-4) M) or DIDS (10(-4) M) suggesting involvement of the Na(+)/H(+) and Cl(-)/HCO(3)(-) exchangers. Cells that were swollen osmotically by an approximately 30% dilution of the extracellular medium also exhibited a limited ability to recover their volume. Therefore, these cells show little ability to volume regulate when exposed to in vitro conditions that shrink or swell the cell.

Mechanoenergetics characterizing oxygen wasting effect of caffeine in canine left ventricle.

Caffeine causes a considerable O(2) waste for positive inotropism in myocardium by complex pharmacological mechanisms. However, no quantitative study has yet characterized the mechanoenergetics of caffeine, particularly its O(2) cost of contractility in the E(max)-PVA-VO(2) framework. Here, E(max) is an index of ventricular contractility, PVA is a measure of total mechanical energy generated by ventricular contraction, and VO(2) is O(2) consumption of ventricular contraction. The E(max)-PVA-VO(2) framework proved to be powerful in cardiac mechanoenergetics. We therefore studied the effects of intracoronary caffeine at concentrations lower than 1 mmol/l on left ventricular (LV) E(max) and VO(2) for excitation-contraction (E-C) coupling in the excised cross-circulated canine heart. We enhanced LV E(max) by intracoronary infusion of caffeine after beta-blockade with propranolol and compared this effect with that of calcium. We obtained the relation between LV VO(2) and PVA with E(max) as a parameter. We then calculated the VO(2) for the E-C coupling by subtracting VO(2) under KCl arrest from the PVA-independent (or zero-PVA) VO(2) and the O(2) cost of E(max) as the slope of the E-C coupling VO(2)-E(max) relation. We found that this cost was 40% greater on average for caffeine than for calcium. This result, for the first time, characterized integratively cardiac mechanoenergetics of the O(2) wasting effect of the complex inotropic mechanisms of intracoronary caffeine at concentrations lower than 1 mmol/l in a beating whole heart.

Particle sizing in strongly turbid suspensions with the one-beam cross-correlation dynamic light-scattering technique.

The utility of the one-beam cross-correlation dynamic light-scattering system for sizing small particles in suspension was previously limited by its small-intensity signal-to-baseline ratio for strongly turbid suspensions. We describe three improvements in the optical system and sample cell that raise the ratio to a value comparable with that of other cross-correlation dynamic light-scattering systems. These improvements are (i) using a square cross-sectional sample cell to minimize the attenuation of the incident beam and singly scattered light, (ii) placing a 200-microm-wide slit between the sample cell and the detector fibers to mask off the region of weak single scattering and strong multiple scattering from the detectors' field of view, and (iii) aligning the center of the detectors' field of view with the region of strongest single scattering. We analyze a number of suspensions of polystyrene latex spheres with a diameter between 65 and 562 nm in water using this improved one-beam instrument and find that the measured radius is determined in a 2-min data collection time to better than +/-10% for volume fractions of the suspended polystyrene latex spheres up to a few percent.

CT brain scans after acute stroke: how far are we from meeting the Scottish intercollegiate guidelines network (SIGN) recommendations? Results from the year prior to guideline publication.

OBJECTIVE: To determine what proportion of patients admitted to Ninewells Hospital & Medical School in 1996 with acute stroke underwent CT brain scans and in what time frame. To decide if the targets set by the SIGN guidelines can be met, and if not, the reasons for this. DESIGN: Data from the Dundee Ninewells Stroke Register and the Computerised Radiology Information System were used to determine the timing of CT scanning in relation to stroke and admission. Notes were also reviewed to determine why CT scans had not been done in some patients. SETTING: Departments of Medicine and Radiology, Ninewells Hospital & Medical School Dundee. SUBJECTS: All patients admitted with acute stroke in the calendar year 1996. RESULTS: Two hundred and eighty six patients presented with acute stroke in 1996. Of these patients, 250 patients (87%) had a CT brain scan. Eighty three (29%) underwent CT brain scanning within 48 hours of the acute event. A total of 163 (57%) were scanned within a week. Two hundred and thirty three (81%) were scanned within three weeks. Thirty six patients were not scanned after their acute event and the reasons recorded are reviewed. CONCLUSIONS: Less than two-thirds of patients were scanned within the time interval of seven days recommended in the SIGN Guidelines for stroke management. Implementation of the current SIGN Guidelines will therefore, require reorganisation of the service to ensure that all patients receive scans within seven and preferably within two days and may have resource implication.

A new integrative method to quantify total Ca2+ handling and futile Ca2+ cycling in failing hearts.

Ca2+ handling in excitation-contraction coupling requires considerable O2 consumption (VO2) in cardiac contraction. We have developed an integrative method to quantify total Ca2+ handling in normal hearts. However, its direct application to failing hearts, where futile Ca2+ cycling via the Ca2+-leaky sarcoplasmic reticulum (SR) required an increased Ca2+ handling VO2, was not legitimate. To quantify total Ca2+ handling even in such failing hearts, we combined futile Ca2+ cycling with Ca2+ handling VO2 and the internal Ca2+ recirculation fraction via the SR. We applied this method to the canine heart mechanoenergetics before and after intracoronary ryanodine at nanomolar concentrations. We found that total Ca2+ handling per beat was halved after the ryanodine treatment from approximately 60 micromol/kg left ventricle before ryanodine. We also found that futile Ca2+ cycling via the SR increased to >1 cycle/beat after ryanodine from presumably zero before ryanodine. These results support the applicability of the present method to the failing hearts with futile Ca2+ cycling via the SR.

2,3-Butanedione monoxime suppresses excitation-contraction coupling in the canine blood-perfused left ventricle.

The negative inotropism of 2,3-butanedione monoxime (BDM) < or = 5 mmol/l has been attributed primarily to directly suppressed crossbridge force development without much suppressed intracellular Ca2+ handling. However, there is evidence that BDM simultaneously or even primarily suppresses myocardial excitation-contraction (E-C) coupling. We therefore studied the mechanoenergetic effects of intracoronary BDM in the left ventricle (LV) of 11 canine excised cross-circulated hearts. We fully utilized the VO2-PVA-Emax framework that we have developed, where VO2 is myocardial O2 consumption, PVA is the systolic pressure-volume area as a measure of the total mechanical energy, and Emax is a contractility index. We gradually depressed Emax from 5.9 to 3.4 mmHg/(ml/100 g) on average by increasing intracoronary BDM to 2.6 +/- 2.1 mmol/l, and then gradually restored Emax to the pre-BDM level by increasing intracoronary CaCl2. We compared the O2 cost of Emax between BDM and Ca2+. We found that BDM and Ca2+ had a similar O2 cost of Emax. BDM did not affect the concentrations of blood-borne catecholamines. We therefore conclude that the negative inotropism of BDM is primarily due to suppressed E-C coupling in canine blood-perfused hearts.

Multiple-scattering suppression by cross correlation.

We describe a new method for characterizing particles in turbid media by cross correlating the scattered intensity fluctuations at two nearby points in the far field. The cross-correlation function selectively emphasizes single scattering over multiple scattering. The usual dynamic light-scattering capability of inferring particle size from decay rate is thus extended to samples that are so turbid as to be visually opaque. The method relies on single-scattering speckle being physically larger than multiple-scattering speckle. With a suitable optical geometry to select nearby points in the far field or equivalently slightly different scattering wave vectors (of the same magnitude), the multiple-scattering contribution to the cross-correlation function may be reduced and in some cases rendered insignificant. Experimental results demonstrating the feasibility of this approach are presented.

Fiber-optics surface-light-scattering spectrometer.

We have developed a fiber-optics surface-light-scattering spectrometer completely designed with optical fiber components. To the best of our knowledge, this is the first demonstration of a noninvasive measurement of the surface tension and the viscosity of simple liquid-vapor interfaces with a fiber-optics-based sensor system. With this approach we obtain a compact size, a significant increase in the signal-to-noise ratio, and the ability to select from a continuum of wave vectors.

Hybrid reflection-transmission surface light-scattering instrument with reduced sensitivity to surface sloshing.

A hybrid reflection-transmission surface light-scattering instrumental design is presented, examined theoretically, and tested experimentally. The purpose of the design is to reduce the sensitivity of the instrument to vibration in general and surface sloshing in particular while sacrificing little performance. Traditional optical arrangements and two new optical configurations with varying trade-offs between slosh resistance and instrumental simplicity and accuracy are examined by use of Fourier optics methods. The most promising design was constructed and tested with acetone, ethanol, and water as subject fluids. The test involved backcalculation of the wave number of the capillary wave examined with the known physical parameters for the test fluids. The agreement of the computed wave number was +/-1.4%.

Ryanodine decreases internal Ca2+ recirculation fraction of the canine heart as studied by postextrasystolic transient alternans.

We tested our hypothesis that the O2 wasting of Ca2+ handling in the excitation-contraction (E-C) coupling in ryanodine-treated failing hearts could be reflected by a decrease in the internal Ca2+ recirculation fraction (RF). We have reported, using canine excised cross-circulated hearts, that intracoronary ryanodine (40 nmol/l blood) halved left ventricular contractility without decreasing myocardial O2 consumption for the E-C coupling. We previously suspected this mechanoenergetic state to manifest energy wasting of Ca2+ handling due to ryanodine causing leakage of Ca2+ from the sarcoplasmic reticulum. To test this hypothesis, we analyzed all the sporadic spontaneous cases of postextrasystolic potentiation (PESP) obtained during the ryanodine experiments. We calculated RF from the beat constant of the exponential decay component of not only the monotonic type but also the transient alternans type of PESP. Results showed that ryanodine significantly decreased the beat constant in both types of PESP from about 2 to 1.5 beats and hence RF from 0.6 to 0.5 on the average, supporting the hypothesis. This organ-level systems approach to Ca2+ handling using transient alternans PESP as well as monotonic PESP may help obtain better insights into the mechanoenergetics of failing hearts.

The effects of cardiac infarction on realistic three-dimensional left ventricular blood ejection.

The effect of cardiac infarction on the flow patterns in cardiac left ventricular ejection was studied using a realistic model which was made from the profile of the left ventricle of a dog heart in diastole. A coordinate measuring machine was used to measure the left ventricular coordinates, and these were input into a three-dimensional flow simulation package. The left ventricular wall motion was described by having the walls moved towards the center of the aortic outlet, and in the case of infarcted tissue, the ventricular wall movement was diminished to simulate infarction flow behavior. The final ventricular volume varied from 25 percent to 54.1 percent of the initial volume in cases without and with infarction, respectively. The maximum blood ejection velocities and ventricular pressure decreased significantly in the presence of infarction. Infarcted areas showed complex blood flow vortex formation not present in the healthy ventricles. The computational technique presented here predicts infarction flow effects which could be observed with measurement techniques such as ultrasound and magnetic resonance imaging, allowing a finer detail of understanding than using either simulation or experimental measurements alone.

Mechanoenergetics of negative inotropism of ventricular wall vibration in dog heart.

Mechanical vibration depresses cardiac contractility. We studied the mechanoenergetic effects of this negative inotropism in the left ventricle (LV) of an isolated, cross-circulated dog heart preparation. We took full advantage of the mechanoenergetic relationship among the LV end-systolic elastance (Emax, contractility index), systolic pressure-volume area (PVA), and myocardial oxygen consumption (VO2). PVA is a measure of the total mechanical energy that cardiac contraction generates. PVA correlates closely with VO2. The VO2 intercept of the VO2-PVA relation reflects the VO2 component for excitation-contraction (E-C) coupling plus basal metabolism (PVA-independent VO2). VO2 above the PVA-independent VO2 reflects the VO2 component for mechanical contraction (PVA-dependent VO2). When we applied 70-Hz vibration of 2-mm amplitude to a LV wall region, it instantly decreased Emax and PVA by 20%, followed by a 10% decrease in VO2 at a fixed volume. However, the vibration neither lowered the VO2-PVA relation obtained at different LV volumes, unlike ordinary negative inotropism, nor changed its slope (1.88 +/- 0.23 vs. 1.86 +/- 0.23 x 10(-5) ml O2.mmHg-1.ml-1). The virtually zero delta PVA-independent VO2/delta Emax with vibration indicates a much smaller O2 cost of Emax than that seen with calcium and propranolol inotropism. These mechanoenergetics support the hypothesis that mechanical vibration primarily suppresses cardiac contractility without suppressing E-C coupling.

Computational fluid mechanical study of the convective heat transfer in a closed space simulating an infant incubator.

The uneven distribution of the ambient temperature in a model of an infant incubator was demonstrated using the computational fluid mechanical (CFM) simulation of the air flow. A finite volume method of CFM calculation was performed on a three-dimensional (3D) model of an infant incubator including a model baby. The time course of the temperature distribution was computed solving the heat transfer equations simultaneously with the momentum equations. An uneven temperature distribution was observed for a long period (60 s) after the warm inflow was introduced into the incubator chamber. The temperature distribution was complex in 3D space and unsteady even after a long time, suggesting that it may take a considerable time to settle and may continue to be unsteady even if the inflow velocity is steady.

Realistic three-dimensional left ventricular ejection determined from computational fluid dynamics.

A realistic model of the left ventricle of the human heart was constructed using a cast from a dog heart which was in diastole. A coordinate measuring machine was used to measure and digitize the coordinates of the left ventricle. From the complex measured left ventricle shape values, a three-dimensional finite volume representation was constructed using a simulation package. The left ventricular walls moved towards the centre of the aortic outlet in order to study the effects of time-varying left ventricular ejection. The left ventricular wall motion was assumed to follow the blood flow and the wall grid was reformed 25 times during the calculation. The 25.8 cm3 ventricular volume was reduced by 75% in 0.25 s. Centreline and cross-sectional velocity vectors greatly increased in magnitude at the aortic outlet, and most of the pressure occurred in the top 15% of the heart. The computational method should make it possible to compare simulation results with important measurement techniques such as ultrasound and magnetic resonance imaging, and this should allow a finer detail of flow understanding than is presently available using either a modelling or imaging method alone.

Cardiac quick-release contraction mechanoenergetics analysis using a cardiac muscle cross-bridge model.

Huxley's sliding filament cross-bridge muscle model coupled with parallel and series elastic components was simulated to examine the conflicting reports on the amount of energy saved by quick release at the peak contraction time. Cross-bridge energy utilization was determined by considering the ATP hydrolysis for the cross-bridge cycling. The quick-release cases were simulated by letting the muscle fiber suddenly shorten to the resting fiber length at peak systole, and then the contraction was allowed to continue at the resting length. Simulation results demonstrated that, using realistic parameter values, typically approximately 15% of the muscle fiber energy is used after peak systole (and approximately 30% of the cross-bridge energy), but this is also a function of the muscle fiber properties characterized by cross-bridge association and dissociation rate constants. Increasing the kinetic rate constants, the series elasticity, the initial fiber length, or the time of peak intracellular calcium will increase the amount of energy left, which may explain some of the discrepancies in the literature. Cardiac muscle hypertrophy will increase the fraction of muscle fiber energy left after peak systole to approximately 30%. The strongest indicator of the percent energy left at peak systole was the time the fiber reached peak systole, and as the fiber reached peak systole faster, the amount of energy saved by quick release increased.

Flow patterns in three-dimensional left ventricular systolic and diastolic flows determined from computational fluid dynamics.

A realistic model of the left ventricle of the heart was previously constructed, using a cast from a dog heart which was in diastole. Previous studies of the three-dimensional heart model were conducted in systole only. The purpose of this investigation was to extend the model to both systole and diastole, and to determine what the effect of a previous cardiac cycle was on the next cardiac cycle. The 25.8 cc ventricular volume was reduced by 40% in 0.25 seconds, then increased to the original volume in another 0.25 seconds and then allowed to rest for 0.25 seconds. Runs done with an ejection fraction of 60% showed little variation from one cardiac cycle to another after the third cardiac cycle was completed; the maximum velocity could vary by over 30% between the first and second cardiac cycles. In systole, centerline and cross-sectional velocity vectors greatly increased in magnitude at the aortic outlet. Most of the pressure drop occurred in the top 15% of the heart. The diastolic phase showed complex vortex formation not seen in the systolic contractions; these complex vortices could account for experimentally observed turbulent blood flow fluctuations in the aorta.

Three-dimensional analysis of left ventricular ejection using computational fluid dynamics.

We present in this study a method for constructing computational fluid mechanical models in order to study the effects of time-varying left ventricular ejection. A spherical left ventricular model was implemented in which three dimensional flow fields were obtained. The time course of the ventricular wall changes were assumed to have a trigonometrically varying nature. The wall grid was reformed 25 times during the calculation since the left ventricular wall motion was assumed to follow the blood flow, and the ventricle wall radius was reduced by 60 percent in 0.25 seconds. Centerline and cross-sectional velocity vectors greatly increased in magnitude at the aortic outlet, and pressure dropped from 1.17 x 10(4) dynes/cm2 (8.8 mmHg) to zero in the top 10 percent of the heart. The modeling framework will be used with left ventricular cast data coordinates in future studies. There is presently a lack of three-dimensional data based on a realistic model, and the computational method should make it possible to compare simulation results with important measurement techniques such as echocardiography and magnetic resonance imaging.

Three-dimensional simulation of blood flow in an abdominal aortic aneurysm--steady and unsteady flow cases.

Atherosclerosis and atherosclerotic aneurysms can occur in the abdominal aorta. Steady and unsteady three-dimensional flow cases were simulated in abdominal aortic aneurysm using a flow simulation package on a graphics workstation. In the steady case, three aneurysm models of 8.0 cm length were simulated using Reynolds numbers of 350 and 700. In the unsteady case, blood flow in a single asymmetric aneurysm of 8.0 cm length was simulated at Reynolds numbers of 350 and 700 and 1400. In the aneurysm center, two symmetric vortices were formed, and flow separation started at the aneurysm inlet. In the unsteady flow case, the main vortex appeared and disappeared and changed position in the unsteady flow case and induced vortices were formed. Although the centerline view shows the vortices change position with time, cross-sectional views show that two symmetric vortices are present or partially formed throughout the entire flow cycle. Regions of high pressure were observed at the aneurysm exit caused by the symmetric vortices that were formed, implying that this high-pressure region could be an area where rupture is most likely. In the unsteady case, regions of maximum pressure moved depending on the flow cycle time; at peak flow, local pressure maximums were observed at the distal aneurysm; these oscillated, tending to put an additional strain on the distal portion of the aneurysm. The shear stress was low in the aneurysm portion of the vessel, and local maximum values were observed at the distal aneurysm constriction.