Graham W. Petley

Ultrasonic propagation in cancellous bone: a new stratified model

The theoretical modeling of ultrasonic propagation in cancellous bone is pertinent to improving the ultrasonic diagnosis of osteoporosis. First, this paper reviews applications of Biots theory to this problem. Next, a new approach is presented, based on an idealization of cancellous bone as a periodic array of bone-marrow layers. Schoenbergs theory is applied to this model to predict wave properties. Bovine bone samples were tested in vitro using pulses centered at 1 MHz over various angles relative to the orientated cancellous structure. Two longitudinal modes (fast and slow waves) were observed for propagation parallel to the structure, but only one was observed for propagation normal to the structure. Angular-dependence of velocities was examined, and the fast wave was found to be strongly anisotropic. These results gave qualitative agreement with predictions of Schoenbergs theory. Although this new model is a simplification of the cancellous architecture, it has potential for future research.

Reference ranges of bone mineral density for women in southern England: the impact of local data on the diagnosis of osteoporosis

The construction of reference ranges that accurately represent the population at large is essential for the correct identification of osteoporosis from bone mineral density (BMD) measurements. In this study, reference data supplied by the manufacturer of the Lunar DPX+ bone densitometer were compared with data obtained locally. Lumbar spine, proximal femur and total body BMD measurements were made in an age-stratified random sample of 702 Southampton women aged 20 to 89 years. Relevant demographic and medical data were recorded for each subject using a questionnaire. Reference curves of BMD (mean +/- SD) were plotted against age for each measurement site and were found to be higher than the manufacturers reference values at all ages and sites. Exclusion of women with factors known to affect bone mass only served to increase this discrepancy. According to World Health Organisation definitions, osteoporosis may be identified from BMD values alone. Based upon neck of femur BMD values, 100 (14.8%) of the women in this study group were categorized as osteoporotic using local young normal reference data, compared with only 39 (5.8%) using the manufacturers data. By normalizing for age distribution, these findings were extrapolated to the local population where it was predicted that 26.0% and 10.1% of females over 50 years of age would be classified as osteoporotic using the respective reference ranges. This study clearly illustrates how the numbers of women diagnosed as osteoporotic vary with the use of different reference populations.

Alcohol consumption alters insulin secretion and cardiac autonomic activity

Background Alcohol may have a cardioprotective effect. One possible mechanism is by modifying insulin resistance/secretion. The aims of this study were: (i) to examine the effect of short‐term alcohol consumption on the metabolic control of glucose tolerance; (ii) to study the influence of short‐term alcohol consumption on cardiac autonomic activity using spectral analysis of heart rate variability.

Gender differences in the relationship between leptin, insulin resistance and the autonomic nervous system

OBJECTIVES Leptin, an important hormonal regulator of body weight, has been shown to stimulate the sympathetic nervous system (SNS) in vitro although the physiological relevance remains unclear. Increased SNS activity has been implicated in the pathogenesis of insulin resistance and an increased cardiovascular risk. We have therefore investigated the relationship between leptin, insulin resistance and cardiac autonomic activity in healthy young adults. 130 healthy men and women age 20.9 years were studied. Insulin sensitivity was assessed using the IVGTT and minimal model with simultaneous measures of leptin. Cardiac autonomic activity was assessed using spectral analysis of heart rate variability. RESULTS Women showed significantly higher fasting leptin, heart rate and cardiac sympathetic activity, and lower insulin sensitivity. Men showed inverse correlations between insulin resistance and heart rate, and between insulin resistance and cardiac sympatho-vagal ratio. Women, in contrast, showed no SNS relationship with insulin resistance, but rather an inverse correlation between leptin and the sympatho-vagal ratio, suggesting that leptin in women is associated with SNS activity. The correlation remained significant after adjustment for BMI and waist-to-hip ratio (beta=-0.33 and p=0.008). CONCLUSION Insulin resistance and SNS activity appear to be linked, although the relationship showed marked gender differences, and the direction of causality was unclear from this cross-sectional study. Leptin appears to exert a greater effect on the SNS in women, possibly because of their greater fat mass.

A novel fifteen minute test for assessment of individual time-dependent clotting responses to aspirin and clopidogrel using modified thrombelastography

Background: A rapid, reliable, point of care test reflecting patient specific responses to antiplatelet therapy would be of great clinical value in percutaneous coronary intervention (PCI). The aim of this study was to establish whether modified thrombelastography (TEG) can be employed as a 15 minute test of individual patient responses to aspirin and clopidogrel using a novel parameter, percentage clotting inhibition (%CIn). Methods and results: Thirty healthy volunteers and 10 patients undergoing elective PCI were recruited into four groups: 10 volunteers received a single 300 mg dose of aspirin [A1]: 10 volunteers received aspirin 75 mg daily for 7 days [A2]: 10 volunteers received a 600 mg dose of clopidogrel [C1]: 10 patients received a 600 mg loading dose of clopidogrel prior to elective PCI [C2]. In all cases the area under the clotting response curve was measured at 15 minutes (AUC15) and used to calculate a novel parameter, percentage clotting inhibition (%CIn). Large differences were demonstrated in both aspirin and clopidogrel groups in response to therapy as assessed by both the area under the curve at 15 minutes and %CIn. Furthermore, the technique demonstrated important heterogeneity of time-dependent responses between individuals. Conclusion: Modified TEG, employing AUC15 and %CIn, is a promising tool for assessing responses to aspirin and clopidogrel. Further data are now required to assess the potential of this test to optimise individual therapy in PCI patients in order to detect and treat those patients with relative hypo-responsiveness to anti-platelet drugs.

Broadband ultrasonic attenuation: are current measurement techniques inherently inaccurate?

Measurements of broadband ultrasonic attenuation (BUA) are currently made using large aperture, piezoelectric transducers. The use of such a receiver is known to lead to the possibility of an overestimate of ultrasonic attenuation due to phase cancellation and it is shown theoretically that this same effect can also lead to an overestimate of BUA. Using a new scanning approach, BUA was measured using two methods, one sensitive to the phase of the acoustic wave, the other not. The phase sensitive BUA measurements were found to be of significantly higher value (p < 0.0001) than the phase insensitive measurements with a mean difference of 31.2 dB MHz-1. These findings are compatible with the hypothesis that BUA measurement systems with large aperture, piezo-electric receivers are inherently inaccurate.

Effects of positive end-expiratory pressure on transthoracic impedance--implications for defibrillation

The success of defibrillation is determined by trans-myocardial current. This current is inversely proportional to transthoracic impedance (TTI). We proposed that increasing lung volume using positive end-expiratory pressure (PEEP) would increase TTI. 12 healthy subjects aged 21-37 years (6 male) were recruited. TTI between self-adhesive defibrillation pads placed in the standard antero-apical position was measured at 30 kHz at end-expiration using Bodystat MultiScan 5000 equipment. PEEP at 2.5, 5.0, 10.0, 20.0 and 40.0 cm H2O was generated using a standard continuous positive airways pressure (CPAP) circuit. Data were analysed using linear regression and paired t-tests comparing baseline TTI with that at a given PEEP. Mean (+/- S.D.) baseline TTI was 65.7 +/- 6.9 omega. TTI increased linearly with increasing PEEP (r2 = 0.99; P < 0.001). Mean percentage increases in TTI were 0.6% at 2.5 cm H2O PEEP (P = 0.05), 1.5%, at 5.0 cm H2O PEEP (P < 0.001), 3.1% at 10.0 cm H2O PEEP (P < 0.001), 5.6% at 20.0 cm H2O PEEP (P < 0.001) and 10.4% at 40.0 cm H2O PEEP (P < 0.001). PEEP increases TTI, proportionately reducing transthoracic current during defibrillation. Clinically, high levels of PEEP (20-40 cm H2O) may occur during ventilation of patients at cardiac arrest and in acute asthmatics. To maximise peak defibrillation current, PEEP should either be minimised prior to defibrillation or consideration should be given to earlier use of high energy levels for defibrillation.

An Investigation of the Diagnostic Value of Bilateral Femoral Neck Bone Mineral Density Measurements

Abstract: This paper describes a study to assess the clinical value of bilateral femoral neck bone mineral density (BMD) measurements. Although a range of factors will determine clinical decisions, the classification of the site with the lowest T-score is likely to have significant bearing on the management of a patient. While it is common practice to measure BMD at the lumbar spine and a single neck of femur, knowledge of the BMD of the second femur may also be of diagnostic value. Using dual-energy X-ray absorptiometry, BMD of the lumbar spine and right and left femoral neck was measured in a group of 2372 white, Caucasian women (mean age ± SD, 56.6 ±13.9 years) routinely referred for bone densitometry. Analysis of the measurements showed a significant (p= 0.02) but small difference between the mean BMD of the right (0.840 ± 0.152 g/cm2) and left (0.837 ± 0.150 g/cm2) femoral neck. Further investigation of femur scans revealed 79 (3.3%) patients in whom one side was osteoporotic while the other side and spine were normal or osteopenic using the World Health Organization diagnostic criteria in combination with manufacturer”s reference data. Patients in whom the femoral neck BMD measurements differed by less than the precision error of the system were then excluded. This left only 51 (2.2%) patients, that is 29 (1.2%) for right femur and spine scan and 22 (0.9%) for left femur and spine scan, in whom knowledge of both femoral neck BMD measurements could have altered the classification of the lowest site assessed to osteoporotic. These data suggest that there is only a small benefit from performing bilateral femoral neck BMD measurements. Since BMD measurements are only one of a range of factors considered as part of a patient”s management, it is suggested that the extra time, cost and radiation dose associated with measurement of the second femur may not be justified.

Determining the optimal paddle force for external defibrillation

In summary, 8-kg paddle force achieves 95% of the overall attainable decrease in TTI when using adult defibrillation paddles placed in an anterior-apical position. We recommend that this is the minimum force that should be applied, with a maximum force of 12 kg if physically possible.

Point-of-care platelet function assays demonstrate reduced responsiveness to clopidogrel, but not aspirin, in patients with Drug-Eluting Stent Thrombosis whilst on dual antiplatelet therapy

BackgroundTo test the hypothesis that point-of-care assays of platelet reactivity would demonstrate reduced response to antiplatelet therapy in patients who experienced Drug Eluting Stent (DES) ST whilst on dual antiplatelet therapy compared to matched DES controls. Whilst the aetiology of stent thrombosis (ST) is multifactorial there is increasing evidence from laboratory-based assays that hyporesponsiveness to antiplatelet therapy is a factor in some cases.MethodsFrom 3004 PCI patients, seven survivors of DES ST whilst on dual antiplatelet therapy were identified and each matched with two patients without ST. Analysis was performed using (a) short Thrombelastogram PlateletMapping™ (TEG) and (b) VerifyNow Aspirin and P2Y12 assays. TEG analysis was performed using the Area Under the Curve at 15 minutes (AUC15) as previously described.ResultsThere were no differences in responses to aspirin. There was significantly greater platelet reactivity on clopidogrel in the ST group using the Accumetrics P2Y12 assay (183 ± 51 vs. 108 ± 31, p = 0.02) and a trend towards greater reactivity using TEG AUC15 (910 ± 328 vs. 618 ± 129, p = 0.07). 57% of the ST group by TEG and 43% of the ST cases by Accumetrics PRU had results > two standard deviations above the expected mean in the control group.ConclusionThis study demonstrates reduced platelet response to clopidogrel in some patients with DES ST compared to matched controls. The availability of point-of-care assays that can detect these responses raises the possibility of prospectively identifying DES patients at risk of ST and manipulating their subsequent risk.