Accuracy of pulse interval timing in ambulatory blood pressure measurement.

Blood pressure (BP) monitors rely on pulse detection. Some blood pressure monitors use pulse timings to analyse pulse interval variability for arrhythmia screening, but this assumes that the pulse interval timings detected from BP cuffs are accurate compared with RR intervals derived from ECG. In this study we compared the accuracy of pulse intervals detected using an ambulatory blood pressure monitor (ABPM) with single lead ECG. Twenty participants wore an ABPM for three hours and a data logger which synchronously measured cuff pressure and ECG. RR intervals were compared with corresponding intervals derived from the cuff pressure tracings using three different pulse landmarks. Linear mixed effects models were used to assess differences between ECG and cuff pressure timings and to investigate the effect of potential covariates. In addition, the maximum number of successive oscillometric beats detectable in a measurement was assessed. From 243 BP measurements, the landmark at the foot of the oscillometric pulse was found to be associated with fewest covariates and had a random error of 9.5 ms. 99% of the cuff pressure recordings had more than 10 successive detectable oscillometric beats. RR intervals can be accurately estimated using an ABPM.

Opportunistic detection of atrial fibrillation using blood pressure monitors: a systematic review.

BACKGROUND: Atrial fibrillation (AF) affects around 2% of the population and early detection is beneficial, allowing patients to begin potentially life-saving anticoagulant therapies. Blood pressure (BP) monitors may offer an opportunity to screen for AF. AIM: To identify and appraise studies which report the diagnostic accuracy of automated BP monitors used for opportunistic AF detection. METHODS: A systematic search was performed of the MEDLINE, MEDLINE In-Process and EMBASE literature databases. Papers were eligible if they described primary studies of the evaluation of a BP device for AF detection, were published in a peer-reviewed journal and reported values for the sensitivity and specificity. Included studies were appraised using the QUADAS-2 tool to assess their risk of bias and applicability to opportunistic AF detection. Values for the sensitivity and specificity of AF detection were extracted from each paper and compared. RESULTS AND CONCLUSIONS: We identified seven papers evaluating six devices from two manufacturers. Only one study scored low risk in all of the QUADAS-2 domains. All studies reported specificity >85% and 6 reported sensitivity >90%. The studies showed that BP devices with embedded algorithms for detecting arrhythmias show promise as screening tools for AF, comparing favourably with manual pulse palpation. But the studies used different methodologies and many were subject to potential bias. More studies are needed to more precisely define the sensitivity and specificity of opportunistic screening for AF during BP measurement before its clinical utility in the population of interest can be assessed fully.

Continuous non-invasive measurement of bladder voiding pressure using an experimental constant low-flow test.

PURPOSE: We developed a prototype device using an automatically controlled inflatable penile cuff to measure bladder voiding pressure continuously and non-invasively in men. The purpose of this study was to validate the pressure measurements made by this device by comparison to those during simultaneous invasive PFS. METHODS: A device was developed to automatically modulate flow rate by controlling pressure in a penile cuff. Men undergoing conventional urodynamics studies were recruited to have an additional fill-void cycle whilst using the new device. We report on 40 men using a standardized protocol. Pressure measured by this device was compared with simultaneous vesical pressure by evaluating maximum pressure during voiding, and calculating the root mean square (RMS) difference between p(cuff) and p(ves) . RESULTS: We recruited 80 men of whom 18 were excluded, 22 were involved in initial development phase and 40 in the standard protocol. Mean (SD) difference between maxima of p(cuff) and p(ves) (1.3 (15.6) cmH(2) O) was not significant. In 20 (50%) men, agreement between p(cuff) and p(ves) throughout the void was moderate or good (RMS difference <20 cmH(2) O). Causes of unsuccessful measurements were identified. CONCLUSIONS: Although a prototype device, this technique appears to be promising for continuous non-invasive bladder pressure measurement. From the results of this study a number of improvements have been recommended and implemented. The next generation of this technique will allow assessment of clinical application.

Characterisation of the expression of the Renin-Angiotensin system in primary and immortalised human renal proximal tubular cells.

BACKGROUND/AIMS: Angiotensin II (AngII) is pivotal in the pathogenesis of progressive kidney disease. We have recently shown that AngII induced an increase in markers of oxidative stress, adaptive responses and upregulated stress-related gene expression in immortalised human proximal tubular (HK-2) cells. However, these observed effects of AngII were not mediated solely via AngII type 1 receptor (ATR1). Both HK-2 cells and primary human renal proximal tubular cells (RPTEC) are useful tools to investigate the renin-angiotensin system (RAS), but data on the local expression of the RAS in these cells remain limited. We therefore characterised RAS expression in RPTEC and HK-2 cells. METHODS: The mRNA and protein expression of RAS in RPTEC and HK-2 cells was examined by RT-PCR, Western blotting and immunoprecipitation. RESULTS: In both cell lines, mRNA for angiotensin-converting enzyme (ACE) and mRNA and protein expression for angiotensinogen, renin, ACE2, ATR1 and ATR4 were detected. Candesartan, a specific ATR1 blocker, effectively blocked the expression of 80% of the stress-related genes that were upregulated in HK-2 cells following exposure to AngII. CONCLUSION: These data support a role for AngII in mediating oxidative stress via other receptor types stimulated by AngII and confirm that it is possible to investigate ATR4 pathways of potential injury in RPTEC.

Interobserver agreement for noninvasive bladder pressure flow recording with penile cuff.

PURPOSE: We assessed variability in interpreting noninvasive measurements of bladder pressure and urine flow between experienced and novice users of the penile cuff. MATERIALS AND METHODS: Urodynamicists at 6 sites were asked to use the penile cuff test as part of clinical assessment in 30 men presenting with lower urinary tract symptoms. After a short training period they measured maximum flow rate and cuff interruption pressure from penile cuff test recordings to enable categorization of bladder outlet obstruction using a nomogram. Similar measurements were then made on the same traces by 2 expert observers from the originating center. Interobserver differences were assessed. RESULTS: Complete agreement on obstruction categorization was seen in 77% of subjects, which increased to 86% when plots positioned on category boundary lines were allocated to the favored category. The 95% confidence limits of interobserver variability in maximum flow rate and cuff interruption pressure measurements were +/- 1.7 ml per second and +/- 13 cm H(2)O, respectively, although a small number of studies yielded discrepancies between observers that were larger than expected. They arose from complex recordings but were equally likely between experts as between expert and novice. Investigation of the causes suggested in some cases how such discrepancies may be avoided in the future. CONCLUSIONS: The excellent level of agreement in measurement and categorization after a short training period suggests that introducing the penile cuff test as part of assessment in men with lower urinary tract symptoms would be straightforward.

Multisite evaluation of noninvasive bladder pressure flow recording using the penile cuff device: assessment of test-retest agreement.

PURPOSE: We performed a pragmatic study of the penile cuff test, a noninvasive method of categorizing bladder outlet obstruction, at a number of United Kingdom urology centers remote from the originating site. We report the agreement of the test and the subsequent retest using the cuff test in the short term. MATERIALS AND METHODS: Men requiring urodynamic investigation for lower urinary tract symptoms were recruited from 6 sites to perform a penile cuff test twice at an interval of approximately 4 weeks. Tests were analyzed by a single interpreter to assess differences in the flow rate, cuff interruption pressure and diagnostic categorization in an individual between the 2 tests due to measurement and physiological error. RESULTS: A total of 136 men (69%) performed 2 suitable cuff tests at a median of 20 days (IQR 8-31). The mean +/- SD difference between the 2 tests in the maximum flow rate was 0.2 +/- 3.7 ml per second and in cuff interruption pressure was 4.0 +/- 26 cm H(2)O. Of the men 33% changed diagnostic category on the Newcastle nomogram, while 47% maintained a consistent diagnosis of obstruction or no obstruction. CONCLUSIONS: Diagnostic category repeatability was similar to that of conventional urodynamics, although there was greater variability in pressure measurements. This supports widespread routine use of the penile cuff test.

Albumin overload induces adaptive responses in human proximal tubular cells through oxidative stress but not via angiotensin II type 1 receptor.

Proteinuria is pathogenic to proximal tubular cells (PTC) and linked with progression to renal failure. The aim of this study was to determine the effects of human serum albumin (HSA) overload on the changes in gene and protein expression stimulated by oxidative stress in PTC and any interaction with ANG II that is pivotal in disease pathogenesis. Markers of oxidative stress, antioxidant defences, transcription factor activation, and the expression of stress-related genes were measured in human PTC (HK-2 cells) overloaded with either globulin-free fatty acid free (GF/FAF) HSA or globulin-free (GF) HSA. The effects of ANG II were also determined. HSA overload in HK-2 cells caused PTC hyperfunction, increased oxidative stress, and an upregulation of adaptive responses and stress-related genes. Some responses were common to both HSAs but others were unique to either HSA and unaffected by addition of ANG II or candesartan (a specific ANG II type 1 receptor blocker). ANG II also independently induced oxidative stress and upregulated other stress-related genes. HSA overload in HK-2 cells stimulated increased oxidative stress and upregulated changes in stress-related gene expression indicating new pathways of PTC injury that are not mediated via ANG II type 1 receptors.

Ascorbic acid supplementation does not attenuate post-exercise muscle soreness following muscle-damaging exercise but may delay the recovery process.

Exercise involving lengthening muscle actions, such as downhill running, results in delayed onset muscle soreness (DOMS), which may be attributable to reactive oxygen species (ROS). Although exercise causes oxidative stress, any link between ROS and DOMS remains speculative. There is emerging evidence to suggest that ROS play an important physiological role, assisting in the recovery process and protecting the cell from future damage; however, this has not been fully established. Despite this uncertainty as to the precise role of ROS, attempts to prevent post-exercise ROS production through antioxidant intervention are still common. The study investigated the effects of ascorbic acid supplementation on ROS production and DOMS following downhill running. Subjects were assigned to two groups. The ascorbic acid group (group AA) received 1 g ascorbic acid 2 h pre-, and for 14 d post-downhill running, whilst the placebo group (Pl group) received a placebo. Blood samples were drawn pre-supplement, pre- and post-exercise, and then 1, 2, 3, 4, 7 and 14 d post-exercise for analysis of ascorbate, malonaldehyde and total glutathione. DOMS was assessed using a visual analogue scale and pressure algometry. Muscle function was assessed using isokinetic dynamometry. Plasma ascorbate was elevated throughout in group AA compared with the Pl group. Downhill running resulted in DOMS in both groups. Muscle function was impaired post-exercise in both groups, although a delayed recovery was noted in group AA. Malonaldehyde increased 4 d post-exercise in the Pl group only. Ascorbic acid supplementation attenuates ROS production following downhill running, without affecting DOMS. Furthermore, ascorbic acid supplementation may inhibit the recovery of muscle function.

Calcineurin inhibitors and proximal renal tubular injury in renal transplant patients with proteinuria and chronic allograft nephropathy.

BACKGROUND: Chronic allograft nephropathy (CAN) is commonly associated with proteinuria. In native nephropathies, proteinuria is linked with proximal renal tubular damage. This study uses regression analysis to link proteinuria with urinary N-acetyl-beta-d-glucosaminidase (NAG) as a marker of tubular injury or hyperfunction in renal transplant patients. METHODS: Proteinuria and urinary NAG were measured and regression analysis applied in 105 transplant patients (42 with CAN). Most were receiving calcineurin inhibitor-based immunosuppression (cyclosporine, n=60; tacrolimus, n=26; and neither drug, n=19). Patients with native nephropathies (n=96) and volunteers (n=21) were also studied. RESULTS: Urinary NAG increased with increasing proteinuria. However, patients taking calcineurin inhibitors had higher urinary NAG at any level of urinary protein than those on alternative therapy, or in native nephropathies. CONCLUSIONS: In groups of transplant patients taking different immunosuppressive regimens, regression analysis of urinary NAG against urinary protein can identify the separate effects of drug-related tubular injury or hyperfunction from that of proteinuria.

Eicosapentaenoic acid and docosahexaenoic acid reduce UVB- and TNF-alpha-induced IL-8 secretion in keratinocytes and UVB-induced IL-8 in fibroblasts.

Omega-3 polyunsaturated fatty acids (n-3 PUFA) inhibit ultraviolet B (UVB)-induced inflammation and other inflammatory states, in vivo. We examined whether this may be mediated by modulation of interleukin (IL)-8, a chemokine pivotal to skin inflammation induced by UVB, in epidermal and dermal cells. We also explored the ability of n-3 PUFA to protect against tumor necrosis factor (TNF)-alpha induction of IL-8, and assessed relative potencies of the principal dietary n-3 PUFA, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Pre-supplementation, both HaCaT keratinocyte and CCD922SK fibroblast cell lines showed dose-responses for UVB-induced IL-8 release (p<0.001), assessed 48 h post-irradiation. Cells were supplemented with > or =90% purified EPA, DHA, oleic acid (OA) or vehicle control, for 4.5 d. EPA and DHA supplements were bioavailable to keratinocytes and fibroblasts. In keratinocytes, EPA and DHA were shown to reduce basal secretion of IL-8 by 66% and 63%, respectively (p<0.05), and UVB-induced levels by 66% and 65% at 48 h after 100 mJ per cm2, respectively, (p<0.01). A similar pattern occurred in fibroblasts, whereas OA had no influence on IL-8 release in either cell line. In addition, TNF-alpha-induced IL-8 secretion by keratinocytes was reduced by 54% and 42%, respectively, by EPA and DHA (p<0.001). Hence both n-3 PUFA inhibit production of UVB- and TNF-alpha-induced IL-8 in skin cells; this may be important in the photoprotective and other anti-inflammatory effects conferred by these agents.

Effects of oral vitamin E and beta-carotene supplementation on ultraviolet radiation-induced oxidative stress in human skin.

BACKGROUND: Ultraviolet radiation (UVR) generates reactive oxygen species in skin that can play a role in skin damage, but reports about the photoprotective properties of oral antioxidant supplements are conflicting. OBJECTIVE: We examined the ability of 2 lipid-soluble antioxidants, vitamin E and beta-carotene, to reduce markers of oxidative stress and erythema in human skin exposed to UVR. DESIGN: Sixteen healthy subjects took either alpha-tocopherol (n = 8; 400 IU/d) or beta-carotene (n = 8; 15 mg/d) for 8 wk. Biopsy samples before and after supplementation were taken from unexposed skin and skin 6 h after 120 mJ/cm(2) UVR. The effects of supplements on markers of oxidative stress in skin and the minimal erythema dose to UVR were assessed. RESULTS: Supplementary vitamin E was bioavailable, the plasma concentration increased from 14.0 +/- 0.66 (x +/- SEM) to 18.2 +/- 0.64 mug/mL (P < 0.01), and the skin concentration increased from 0.55 +/- 0.09 to 1.6 +/- 0.19 ng/mg protein (P < 0.01). Supplementary beta-carotene increased plasma concentrations from 1 +/- 0.3 to 2.25 +/- 0.3 mug/mL (P < 0.05), but skin concentrations were undetectable. Before vitamin E supplementation, UVR increased the skin malondialdehyde concentration from 0.42 +/- 0.07 to 1.24 +/- 0.16 nmol/mg protein (P < 0.01), whereas oxidized or total glutathione increased from 9.98 +/- 0.4% to 12.0 +/- 1.0% (P < 0.05). Vitamin E supplementation significantly decreased the skin malondialdehyde concentration, but neither vitamin E nor beta-carotene significantly influenced other measures of oxidation in basal or UVR-exposed skin. CONCLUSIONS: Vitamin E or beta-carotene supplementation had no effect on skin sensitivity to UVR. Although vitamin E supplements significantly reduced the skin malondialdehyde concentration, neither supplement affected other measures of UVR-induced oxidative stress in human skin, which suggested no photoprotection of supplementation.

Large firms' retiree health benefits before Medicare reform: 2003 survey results.

This survey of large, private-sector employers offering retiree health benefits in 2003 provides a detailed baseline of private retiree health plans on the eve of the most sweeping changes to Medicare since its enactment. Total retiree health costs rose 13.7 percent in 2003, and average retiree contributions to premiums for employees age sixty-five and older retiring in 2003 rose 18 percent. Nearly half of surveyed employers have capped their contributions to health coverage for retirees over age sixty-five. Before passage of the new Medicare legislation, 20 percent said that they are likely to eliminate benefits for future retirees within three years.

Oxidative stress in a novel model of chronic acidosis in LLC-PK1 cells.

Chronic metabolic acidosis occurs commonly in chronic renal failure (CRF). The proximal renal tubular cell is the site in the kidney of high oxidative metabolic activity and in CRF is associated with adaptive hypertrophy and hypermetabolism. We hypothesised that chronic acidosis may lead to increased generation of reactive oxygen species due to increased oxidative activity. We developed a novel model of chronic acidosis in LLC-PK1 cells and measured markers of oxidative stress and metabolism. Acidosis led to a reduction in cellular total glutathione and protein thiol content and an increase in glutathione peroxidase activity and NH3 generation. The expression of constitutively expressed heat stress protein (HSP) HSC70 and HSP60 increased at pH 7.0.