Comparative phase imaging of live cells by digital holographic microscopy and transport of intensity equation methods.

We describe a microscopic setup implementing phase imaging by digital holographic microscopy (DHM) and transport of intensity equation (TIE) methods, which allows the results of both measurements to be quantitatively compared for either live cell or static samples. Digital holographic microscopy is a well-established method that provides robust phase reconstructions, but requires a sophisticated interferometric imaging system. TIE, on the other hand, is directly compatible with bright-field microscopy, but is more susceptible to noise artifacts. We present results comparing DHM and TIE on a custom-built microscope system that allows both techniques to be used on the same cells in rapid succession, thus permitting the comparison of the accuracy of both methods.

Hemodynamic Response to Exercise for Prediction of Development of Kidney Failure: Revealing a Cardiorenal Secret Cross Talk.

INTRODUCTION: Kidney disease increases the risk of cardiovascular disease. The corollary of that observation should be that cardiovascular disease would not only increase the risk of kidney dysfunction, but also cause kidney damage, a concept not previously proposed. MATERIALS AND METHODS: Hemodynamic response to a graded exercise stress test was measured in 70 candidates to evaluate the association of heart rate and blood pressure change, heart rate reserve, chronotropic incompetence (percentage of achievement of maximal predicted heart rate), and circulatory power with development of kidney failure (glomerular filtration rate < 30 mL/min/1.73 m2) during 123 months of follow-up period. RESULTS: Kidney failure was more likely to develop in patients with lower heart rate change, heart rate reserve, percentage of achievement of maximal predicted heart rate, and circulatory power (P = .002, P = .01, P = .02, and P = .008, respectively), even after adjustment for age, resting pulse pressure, hypertension, diabetes mellitus, and exercise test result (hazard ratios, 5.9, 2.9, 3.3, and 2.9, respectively). A resting pulse pressure of 60 mm Hg and higher was accompanied by 7.4 times (95% confidence interval, 1.8 to 30.9) greater risk of developing kidney failure, independent of age and resting systolic blood pressure (P = .006). CONCLUSIONS: Hemodynamic responses to a standard graded exercise stress test independently predicted the development of kidney failure. Also, arterial stiffness (represented by resting pulse pressure) could be a factor linking ventricular and kidney function. Early diagnosis of kidney disease should include a cardiovascular assessment and vice versa.

The Effect of Body Mass on the 30-15 Intermittent Fitness Test in Rugby Union Players.

PURPOSE: To evaluate the difference in performance of the 30-15 Intermittent Fitness Test (30-15IFT) across 4 squads in a professional rugby union club in the UK and consider body mass in the interpretation of the end velocity of the 30-15IFT (VIFT). METHODS: One hundred fourteen rugby union players completed the 30-15IFT midseason. RESULTS: VIFT demonstrated small and possibly lower (ES = -0.33; 4/29/67) values in the under 16s compared with the under 21s, with further comparisons unclear. With body mass included as a covariate, all differences were moderate to large and very likely to almost certainly lower in the squads with lower body mass, with the exception of comparisons between senior and under-21 squads. CONCLUSIONS: The data demonstrate that there appears to be a ceiling to the VIFT attained in rugby union players that does not increase from under-16 to senior level. However, the associated increases in body mass with increased playing level suggest that the ability to perform high-intensity running increases with age, although not translating into greater VIFT due to the detrimental effect of body mass on change of direction. Practitioners should be aware that VIFT is unlikely to improve, but it needs to be monitored during periods where increases in body mass are evident.

Circulatory syndrome: an evolution of the metabolic syndrome concept!

The metabolic syndrome has been a useful, though controversial construct in clinical practice as well as a valuable model in order to understand the interactions of diverse cardiovascular risk factors. However the increasing importance of the circulatory system in particular the endothelium, in both connecting and controlling organ function has underlined the limitations of the metabolic syndrome definition. The proposed "Circulatory Syndrome" is an attempt to refine the metabolic syndrome concept by the addition of recently documented markers of cardiovascular disease including renal impairment, microalbuminuria, arterial stiffness, ventricular dysfunction and anaemia to more classic factors including hypertension, dyslipidemia and abnormal glucose metabolism; all of which easily measured in clinical practice. These markers interact with each other as well as with other factors such as aging, obesity, physical inactivity, diet and smoking. The final common pathways of inflammation, oxidative stress and hypercoagulability thereby lead to endothelial damage and eventually cardiovascular disease. Nevertheless, the Circulatory (MARC) Syndrome, like its predecessor the metabolic syndrome, is only a small step toward an understanding of these complex and as yet poorly understood markers of disease.

What's in a name? Brand name confusion and generic medicines.

We need an urgent review of medicines labelling in Australia and New Zealand.

Evaluation of arterial stiffness and pulse wave reflection for cardiovascular risk assessment in diabetic and nondiabetic kidney transplant recipients.

INTRODUCTION: Evidence demonstrates that cardiovascular risk reduces after kidney transplantation, but is still a major cause of death. With increasing inclusion of diabetic patients for kidney transplantation, the evaluation of cardiovascular disease in this population becomes more important. We compared arterial stiffness and pulse wave reflection as well as other cardiovascular risk factors in kidney transplant patients with and without diabetes mellitus. MATERIALS AND METHODS: One hundred kidney transplant recipients, including 33 diabetic patients, were evaluated for their renal-cardiovascular risk factors, including blood pressure, lipids, glucose control, homocysteine, and arterial stiffness indexes. The tests were repeated after 1 year in 47 individuals. RESULTS: There was no significant difference in pulse wave velocity (PWV) between the diabetic and nondiabetic groups, despite a greater augmentation index (AI) in the diabetic group (20.5 +/- 2.3 versus 13.1 +/- 2.2). Multivariable analysis revealed that diabetes mellitus was a significant determinant for AI independently of age, blood pressure, posttransplant time, gender, and glomerular filtration rate (R2 = 39%). Repeated test after 1 year demonstrated a significant reduction in the carotid-femoral PWV (P = .03) and systolic blood pressure (P = .007). CONCLUSIONS: In contrast to nontransplant groups, AI was significantly greater in diabetic kidney transplant patients compared to their nondiabetic counterparts, despite a comparable PWV. However, carotid-femoral PWV improved after 1 year. These may reflect progressive ventricular and large arterial function improvement despite remained small arterial defects after transplantation. It also suggests potential role of arterial evaluation in risk assessment among kidney transplant patients.

The impact of arm position and pulse pressure on the validation of a wrist-cuff blood pressure measurement device in a high risk population.

Despite the increasing popularity of blood pressure (BP) wrist monitors for self-BP measurement at home, device validation and the effect of arm position remains an issue. This study focused on the validation of the Omron HEM-609 wrist BP device, including an evaluation of the impact of arm position and pulse pressure on BP measurement validation. Fifty patients at high risk for cardiovascular disease were selected (age 65 +/- 10 years). Each patient had two measurements with a mercury sphygmomanometer and three measurements with the wrist BP device (wrist at the heart level while the horizontal arm supported [HORIZONTAL], hand supported on the opposite shoulder [SHOULDER], and elbow placed on a desk [DESK]), in random order. The achieved systolic BP (SBP) and diastolic BP (DBP) wrist-cuff readings were compared to the mercury device and the frequencies of the readings within 5, 10, and 15 mmHg of the gold standard were computed and compared with the British Hypertension Society (BHS) and Association for the Advancement of Medical Instrumentation (AAMI) protocols. The results showed while SBP readings with HORIZONTAL and SHOULDER positions were significantly different from the mercury device (mean difference = 7.1 and 13.3 mmHg, respectively; P < 0.05), the DESK position created the closest reading to mercury (mean difference = 3.8, P > 0.1). Approximately 71% of SBP readings with the DESK position were within +/-10 mmHg, whereas it was 62.5% and 34% for HORIZONTAL and SHOULDER positions, respectively. Wrist DBP attained category D with BHS criteria with all three arm positions. Bland-Altman plots illustrated that the wrist monitor systematically underestimated SBP and DBP values. However a reading adjustment of 5 and 10 mmHg for SBP and DBP (DESK position) resulted in improvement with 75% and 77% of the readings being within 10 mmHg (grade B), respectively. AAMI criteria were not fulfilled due to heterogeneity. The findings also showed that the mismatch between the mercury and wrist-cuff systolic BP readings was directly associated with pulse pressure. In conclusion the DESK position produces the most accurate readings when compared to the mercury device. Although wrist BP measurement may underestimate BP measured compared to a mercury device, an adjustment by 5 and 10 mmHg for SBP and DBP, respectively, creates a valid result with the DESK position. Nevertheless, considering the observed variations and the possible impact of arterial stiffness, individual clinical validation is recommended.

Arterial stiffness in kidney transplant recipients: an overview of methodology and applications.

INTRODUCTION: Cardiovascular disease is still a major cause of mortality in kidney transplant patients. This is partially attributed to the nonclassic cardiovascular risk factors including arterial stiffness, an established independent predictor of mortality in several patient populations. MATERIALS AND METHODS: An extensive search was performed to review the evolution process of the method for arterial stiffness assessment and sphygmology and their applications in chronic kidney disease before and after kidney transplantation. RESULTS: Despite a marked change in methodology from the ancient medical practice to the current modern medicine, noninvasive assessment of arterial stiffness is still based on pulse analysis. Currently, pulse wave velocity, augmentation index, and pulse wave reflection are preferred indexes for arterial stiffness. Increased arterial stiffness has been reported in diabetes mellitus, hypertension, chronic kidney disease, cardiovascular disease, and elderly, and reduction of arterial stiffness is a key element for efficacy of the treatment and mortality reduction. CONCLUSION: Noninvasive assessment of arterial stiffness is suggested as a part of clinical assessment for kidney transplant recipients and donors and facilitates defining high-risk patients for development of cardiovascular disease. A combination of techniques is recommended for this purpose.

Potential roles of erythropoietin in the management of anaemia and other complications diabetes.

Erythropoietin (EPO) is a haematopoietic cytokine, mainly generated in the renal cortex, and its secretion and action is impaired in chronic kidney disease (CKD). Early renal damage in diabetes mellitus (DM) is usually not detected because diabetes-induced nephron hypertrophy maintains glomerular filtration rate (GFR) and an elevated plasma creatinine concentration is a relatively late manifestation of diabetic nephropathy. However, anaemia occurs more frequently in subjects with DM when compared with those with non-DM renal disease. While reduced production and a blunted response to EPO occurs in DM with early renal damage, other factors including chronic inflammation, autonomic neuropathy and iron deficiency are also important. Although recombinant human erythropoietin (rhEPO) has been an effective therapeutic agent in CKD anaemia, it appears to be more effective in patients with DM, even in earlier stages. Nevertheless, patients with DM are also more likely to be iron deficient, a barrier to effective rhEPO therapy. The effect of treatment on the reliability of haemoglobin A(1c) as an index of glycaemic control must be remembered. It is proposed that anaemia and its causes must be important components of care in subjects with early diabetic renal damage.

Better management of cardiovascular diseases by pulse wave velocity: combining clinical practice with clinical research using evidence-based medicine.

Arterial stiffness measured by pulse wave velocity (PWV) is an accepted strong, independent predictor of cardiovascular events and mortality. However, lack of a reliable reference range has limited its use in clinical practice. In this evidence-based review, we applied published data to develop a PWV risk stratification model and demonstrated its impact on the management of common clinical scenarios. After reviewing 97 studies where PWV was measured, 5 end-stage renal disease patients, 5 hypertensives, 2 diabetics, and 2 elderly studies were selected. Pooling the data by the "fixed-effect model" demonstrated that the mortality and cardiovascular event risk ratio for one level increment in PWV was 2.41 (1.81-3.20) or 1.69 (1.35-2.11), respectively. There was a significant difference in PWV between survived and deceased groups, both in the low and high risk populations. Furthermore, risk comparison demonstrated that 1 standard deviation increment in PWV is equivalent to 10 years of aging, or 1.5 to 2 times the risk of a 10 mmHg increase in systolic blood pressure. Evidence shows that PWV can be beneficially used in clinical practice for cardiovascular risk stratification. Furthermore, the above risk estimates could be incorporated into currently used cardiac risk scores to improve their predictive power and facilitate the clinical application of PWV.

Disturbed hemodynamic cardiac exercise stress test response in non-smoking, normolipidemic, normotensive, diabetic subjects.

OBJECTIVE: The hemodynamic response to exercise is affected by diverse factors such as age, gender and exercise load as well as concomitant pathogenic conditions including smoking, hyperlipidemia, hypertension and possibly diabetes. In this study the hemodynamic response to a graded exercise has been evaluated in diabetic and non-diabetic individuals. DESIGN AND METHOD: In 3170 consecutive non-smoker normolipidemic normotensive patients, referred for the treadmill exercise test (age 25-70 years), the exercise-induced change in heart rate (DeltaHR) and blood pressure (DeltaSBP and DeltaDBP) was evaluated in 176 diabetics (DM) compared to non-diabetics (NDM). RESULTS: The results demonstrated that while resting HR and SBP were higher in DM, they had an impaired DeltaHR (62.1+/-20.5 versus 76.4+/-24.2; P<0.0001), DeltaSBP (35.5+/-29.3 versus 42.2+/-24.5; P<0.01) and DeltaDBP (-0.4+/-9.8 versus 2.1+/-15.9; P<0.05) in response to exercise compared to NDM, even among individuals with negative results for exercise test. DM had also lower heart rate reserve, circulatory power and rate-pressure product than NDM (all P<0.0001). While DM were slightly older (57 versus 54.5) and had lower exercise capacity (7.1 versus 8.6 MET) than NDM (both P<0.01), the impact of DM on the hemodynamic changes remained independent and significant after multivariate adjustment for age, exercise load and gender for DeltaHR and DeltaSBP (P<0.01). Exercise-induced DeltaSBP was directly correlated with exercise load and inversely associated with resting pulse pressure (rPP) (P<0.0001). Furthermore, rPP was the second strongest independent predictor for DeltaSBP (beta=-0.22, p<0.0001). CONCLUSION: The impaired hemodynamic response of DM to exercise and its inverse association with rPP supports the early development of arterial and ventricular stiffness in DM, unrelated to other likely risk factors such as hypertension and hyperlipidemia.

Estimation of an age-specific reference interval for pulse wave velocity: a meta-analysis.

OBJECTIVE: To estimate an age-specific reference interval for carotid-femoral pulse wave velocity (PWV), an index of aortic stiffness, and to determine the predictive values of the reference range for detecting those at moderate and high risk of cardiovascular disease (CVD). DESIGN AND METHODS: We searched MEDLINE using PubMed from 1995 to 2005 for all studies in which Carotid-Femoral PWV was measured using a Complior (Colson, Paris, France) apparatus in Caucasian non-pregnant adults. Twenty-five studies were included, covering 30 groups of subjects; these groups were classified a priori into low (normal), moderate, and high CVD risk categories, with 2008, 5979, and 180 (total 8167) subjects, respectively. Individual-level data were simulated for each group, and an age-specific reference interval was calculated by using fractional polynomial functions. RESULTS: We plotted an age-adjusted normal curve for PWV with 2.5, 5, 50, 90, 95, and 97.5 centile limits. Applying this reference interval to the moderate- and high-risk groups using simulations yielded sensitivities of 34.3 [95% confidence interval (CI) 33.2-35.3] and 57.2 (95% CI 55.2-59.3), respectively, specificities of 95.3 (95% CI 94.8-95.8) and 95.3 (95% CI 94.4-96.2), respectively, and positive likelihood ratios of 7.3 and 12.2, respectively. CONCLUSION: We constructed an age-adjusted reference curve for PWV. Using the 95th centile of this curve as a threshold (e.g. 10.94, 11.86, and 13.18 m/s for 20, 40, and 60 years old) shows construct validity, as it appears to identify medium and high CVD risk groups reasonably accurately. This reference range needs to be tested using other datasets.

Haemodialysis-unresponsive blood pressure: cardiovascular mortality predictor?

AIM: The importance of 'conventional' cardiovascular risk factors in haemodialysis (HD) patients has been questioned following evidence that pre-HD blood pressure (BP) might be inversely related to mortality in contrast to post-HD BP. To evaluate this reverse BP epidemiology in HD patients, HD-induced BP changes were compared with aortic pulse wave velocity (PWV), an independent predictor of cardiovascular mortality. METHOD: Aortic PWV was evaluated in a limited care HD cohort, all of whom were asymptomatic of cardiovascular disease. RESULTS: Of 47 limited care patients, 45% were classified as HD responsive, with a 17% fall in mean arterial pressure compared with a 6% increase in the HD-unresponsive group. While there were no significant differences between the two groups in traditional vascular disease risk factors or interdialytic weight loss, PWV was significantly elevated in the HD-unresponsive group (12.9 +/- 2.7 compared with 10.8 +/- 2.9; P < 0.05). Furthermore, there was a positive correlation between the change in BP during HD and PWV in all subjects (r = 0.500; P < 0.001 for systolic blood pressure (SBP), a correlation that also existed for diastolic blood pressure (DBP) (P < 0.01). CONCLUSION: This study suggests that patients with HD-unresponsive BP are more likely to have vascular disease and this association between PWV and HD-induced BP changes might partly explain the apparent paradox of pre- and post-HD BP with mortality. It is proposed that a population with elevated post-HD BP is more likely to be composed of subjects with vascular disease (overt or occult), in contrast to a group with high pre-HD BP, which will be more heterogeneous.

Direct comparison of repeated same-day self and ambulatory blood pressure monitoring.

BACKGROUND AND AIM: The relative roles of self and ambulatory blood pressure monitoring (self BPM, ABPM, respectively) have yet to be clearly defined despite accumulating evidence of self BPM benefits, particularly in hypertension management. In particular, measurements comparable to ABPM have been documented with self-measurement, usually twice daily over one or more days. Nevertheless, ABPM offers a series of recordings performed throughout the day that can be invaluable during drug treatment. Consequently, this study evaluated 18 normotensive and 79 hypertensive patients, including 21 not taking hypotensive agents, and measured their blood pressure at least every 2 h while they were also undergoing ABPM. METHODS AND RESULTS: Self-measurement was performed between five and 12 times during the day with 77% of subjects preferring self BPM rather than daytime ABPM. When compared with the closest ABP measurement, mean systolic and diastolic pressures were not significantly different throughout the day in both normotensive and hypertensive patients. However, a comparison of a series of ABPM hourly averages (three readings performed closest to the respective self BPM reading) throughout the day in all hypertensive subjects found ABPM readings to be slightly but significantly lower (3.3 systolic, 2.2 mmHg diastolic; P < 0.05). CONCLUSION: It is concluded that multiple self-measurements throughout the day provides comparable information to daytime ABPM, is preferred by most patients, and should be a cost-effective alternative in the diagnosis and management of hypertension.

Inaccuracy of wrist-cuff oscillometric blood pressure devices: an arm position artefact?

BACKGROUND: Despite the increasing popularity of wrist-cuff blood pressure (BP) devices, their accuracy has not been established and international guidelines do not support their use. Because arm position influences BP measurement, it is possible that conflicting reports on wrist-cuff device accuracy reflects diverse arm positions. METHOD: This study compared BP measured by two oscillometric devices, the upper arm-cuff OMRON HEM 705 CP and the OMRON R6 oscillometric wrist-cuff device. In the former BP was measured with the arm in two supported positions, dependent on a table (manufacturer's instructions) and horizontal (mid sternum), while the latter followed the manufacturer's instructions. RESULTS: In contrast to the dependent arm where BP was significantly higher (P<0.05), the horizontal arm position with the arm-cuff produced a mean systolic and diastolic BP comparable to the wrist-cuff device where the wrist was at heart level being respectively, 137+/-29/80+/-16 and 134+/-27/77+/-16 mmHg. A close relationship over a wide BP range was also confirmed by least squares, least product linear regression and Bland-Altman analysis. CONCLUSION: This study supports the use of wrist-cuff monitors for self/home use and underlines the need for a more precise definition for arm position when using all BP devices -- mercury and oscillometric.

Chronic kidney disease and automatic reporting of estimated glomerular filtration rate: a position statement.

The systematic staging of chronic kidney disease (CKD) by glomerular filtration measurement and proteinuria has allowed the development of rational and appropriate management plans. One of the barriers to early detection of CKD is the lack of a precise, reliable and consistent measure of kidney function. The most common measure of kidney function is currently serum creatinine concentration. It varies with age, sex, muscle mass and diet, and interlaboratory variation between measurements is as high as 20%. The reference interval for serum creatinine concentration includes up to 25% of people (particularly thin, elderly women) who have an estimated glomerular filtration rate (eGFR) that is significantly reduced (< 60 mL/min/1.73 m). The recent publication of a validated formula (MDRD) to estimate GFR from age, sex, race and serum creatinine concentration, without any requirement for measures of body mass, allows pathology laboratories to "automatically" generate eGFR from data already acquired. Automatic laboratory reporting of eGFR calculated from serum creatinine measurements would help to identify asymptomatic kidney dysfunction at an earlier stage. eGFR correlates well with complications of CKD and an increased risk of adverse outcomes such as cardiovascular morbidity and mortality. We recommend that pathology laboratories automatically report eGFR each time a serum creatinine test is ordered in adults. As the accuracy of eGFR is suboptimal in patients with normal or near-normal renal function, we recommend that calculated eGFRs above 60 mL/min/1.73 m be reported by laboratories as "> 60 mL/min/1.73 m", rather than as a precise figure.

Acute effect of haemodialysis on arterial stiffness: membrane bioincompatibility?

BACKGROUND: Repetitive endothelial damage from dialysis membrane incompatibility is a probable cause of accelerated atherosclerosis in haemodialysis patients. Consequently pulse wave velocity (PWV), a measure of arterial stiffness, was utilized as a surrogate marker of vascular dysfunction during dialysis with two commonly used synthetic dialysers. METHODS: PWV was monitored before, during and after haemodialysis using both polysulphone and polyamide membranes. PWV, an arterial stiffness measure, was calculated from the carotid to the femoral (C-F) and also to the radial (C-R) artery. In a further group, PWV was monitored while polysulphone and polyamide membranes were perfused with blood without dialysate. RESULTS: Mean aortic (C-F) PWV was lower during dialysis with the polyamide membrane, being 14 and 16% less following 75 and 135 min of dialysis (P<0.05) in 24 patients. Because intradialytic intravascular volume changes alter PWV, a subgroup analysis in 11 patients where dialysis fluid removal during both periods was minimal (<1 kg) was performed, and a persistent and significant increase in aortic PWV was detected with the polysulphone kidney being maximal (40%) at 75 min (P<0.01). This increase was negatively correlated with pre-dialysis PWV (P<0.01). In contrast, the polyamide dialyser did not change PWV. An increase in C-R PWV was also noted with the polysulphone membrane (P<0.05). In the nine patients where membranes were perfused with blood without dialysate, aortic PWV was again significantly increased by the polysulphone (P<0.01), but not the polyamide dialyser. CONCLUSIONS: Haemodialysis with polysulphone but not polyamide membranes acutely alters aortic 'stiffness', an effect postulated to be due to membrane bioincompatibility. However, factors including age, time on dialysis and underlying vascular disease, were also found to impact on these acute dialysis-induced changes to vascular function. Since these acute changes disappear post-dialysis, their long-term consequences are uncertain.