The difference in blood pressure readings between arms and survival: primary care cohort study

addresses: Primary Care Research Group, Institute of Health Services Research, Peninsula College of Medicine and Dentistry, University of Exeter, Devon EX1 2LU, UK. [email protected]: PMCID: PMC3309155To determine whether a difference in systolic blood pressure readings between arms can predict a reduced event free survival after 10 years

Effect of an oxygen pressure injection (OPI) device on the oxygen saturation of patients during dermatological methyl aminolevulinate photodynamic therapy

Journal Article“The final publication is available at Springer via http://dx.doi.org/10.1007/s10103-012-1188-y"Methyl aminolevulinate photodynamic therapy (MAL-PDT) (a topical treatment used for a number of precancerous skin conditions) utilizes the combined interaction of a photosensitizer (protoporphyrin IX (PpIX)), light of the appropriate wavelength, and molecular oxygen to produce singlet oxygen and other reactive oxygen species which induce cell death. During treatment, localized oxygen depletion occurs and is thought to contribute to decreased efficacy. The aim of this study was to investigate whether an oxygen pressure injection (OPI) device had an effect on localized oxygen saturation levels and/or PpIX fluorescence of skin lesions during MAL-PDT. This study employed an OPI device to apply oxygen under pressure to the skin lesions of patients undergoing standard MAL-PDT. Optical reflectance spectrometry and fluorescence imaging were used to noninvasively monitor the localized oxygen saturation and PpIX fluorescence of the treatment area, respectively. No significant changes in oxygen saturation were observed when these data were combined for the group with OPI and compared to the group that received standard MAL-PDT without OPI. Additionally, no significant difference in PpIX photobleaching or clinical outcome at 3 months between the groups of patients was observed, although the group that received standard MAL-PDT demonstrated a significant increase (p < 0.05) in PpIX fluorescence initially and both groups produced a significant decrease (p < 0.05) after light irradiation. In conclusion, with this sample size, this OPI device was not found to be an effective method with which to improve tissue oxygenation during MAL-PDT. Further investigation is therefore required to find a more effective method of MAL-PDT enhancement. © 2012 Springer-Verlag London Ltd

Stability of urinary albumin and creatinine after 12 months storage at -20 °C and -80 °C.

Increasing albumin to creatinine ratio (ACR) within the normal range is a risk factor for cardiovascular disease in the general population. Clinical and epidemiological studies often store urine samples for long durations prior to ACR assessment. The stability of ACR at the lowest urinary albumin concentrations during prolonged storage has not been previously studied because routine clinical assays can't quantify very low concentrations of albumin.This article is freely available via Open Access. Click on the Publisher URL to access.Published (Open Access

The difference in blood pressure readings between arms and survival: primary care cohort study

Objective To determine whether a difference in systolic blood pressure readings between arms can predict a reduced event free survival after 10 years

Oxygen saturation and perfusion changes during dermatological methylaminolaevulinate photodynamic therapy

Journal ArticleResearch Support, Non-U.S. Gov't"This is the peer reviewed version of the following article: British Journal of Dermatology, Volume 165, Issue 6, pages 1323–1331, December 2011, which has been published in final form at http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2133.2011.10554.x/abstract. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving."BACKGROUND: Methylaminolaevulinate (MAL)-photodynamic therapy (PDT) is a successful topical treatment for a number of (pre)cancerous dermatological conditions. In combination, light of the appropriate wavelength, the photosensitizer protoporphyrin IX (PpIX) and tissue oxygen result in the production of singlet oxygen and reactive oxygen species inducing cell death. OBJECTIVES: This study investigates real-time changes in localized tissue blood oxygen saturation and perfusion in conjunction with PpIX fluorescence monitoring for the first time during dermatological MAL-PDT. METHODS: Oxygen saturation, perfusion and PpIX fluorescence were monitored noninvasively utilizing optical reflectance spectroscopy, laser Doppler perfusion imaging and a fluorescence imaging system, respectively. Patients attending for standard dermatological MAL-PDT were recruited to this ethically approved study and monitored prior to, during and after light irradiation. RESULTS: Significant reductions in mean blood oxygen saturation (P < 0·005) and PpIX fluorescence (P < 0·001) were observed within the first minute of irradiation (4·75 J cm(-2) ) while, in contrast, perfusion was observed to increase significantly (P < 0·01) during treatment. The changes in oxygen saturation and PpIX fluorescence were positively correlated during the initial phase of treatment (r(2) = 0·766). CONCLUSIONS: Rapid reductions in the localized blood oxygen saturation have been observed for the first time to occur clinically within the initial minutes of light irradiation and positively correlate with the concurrent PpIX photobleaching. Furthermore, perfusion increases, suggesting that the microvasculature compensates for the PDT-induced oxygen depletion

Detection of Staphylococcal Cassette Chromosome mec Associated DNA Segments in Multiresistant MSSA and Identification of Staphylococcus epidermidis ccrAB4

Methicillin-susceptible Staphylococcus aureus (MSSA) can arise from methicillin-resistant S. aureus (MRSA) following partial or complete excision of staphylococcal cassette chromosome mec (SCCmec). This study investigated whether multiresistant MSSA isolates from Irish hospitals, where MRSA has been endemic for decades, harbor SCCmec DNA. Twenty-five multiresistant MSSA isolates recovered between 2002 and 2006 were tested for SCCmec DNA by PCR and were genotyped by multilocus sequence typing and spa typing. All isolates lacked mecA. Three isolates (12%) harbored SCCmec DNA; two of these (genotype ST8 t190) harbored a 26-kb SCCmec IID (II.3.1.2) remnant that lacked part of mecI and all of mecR1, mecA, and IS431; the third isolate (ST8 t3209) harbored the SCCmec region from dcs to orfX. All three isolates were detected as MRSA using the BD GeneOhm and Cepheid’s Xpert MRSA real-time PCR assays. Six isolates, including both isolates with the SCCmec IID remnant, harbored ccrAB4 with 100% identity to ccrAB4 from the Staphylococcus epidermidis composite island SCC CI. This ccrAB4 gene was also identified in 23 MRSA isolates representative of ST8 t190 MRSA with variant SCCmec II subtypes IIA to IIE, which predominated previously in Irish hospitals. ccrAB4 was located 5,549 bp upstream of the left SCCmec junction in both the MRSA and MSSA isolates with SCCmec elements and remnants and 5,549 bp upstream of orfX in the four MSSA isolates with ccrAB4 only on an SCC CI homologous region. This is the first description of a large SCCmec remnant with ccr and partial mec genes in MSSA and of the S. epidermidis SCC CI and ccrAB4 genes in S. aureus

Circulating soluble IL-6 receptor associates with plaque inflammation but not with atherosclerosis severity and cardiovascular risk

Background: The residual cardiovascular risk in subjects receiving guideline-recommended therapy is related to persistent vascular inflammation and IL-6 represents a target for its treatment. IL-6 binds to receptors on leukocytes and hepatocytes and/or by forming complexes with soluble IL-6 receptors (sIL-6R) binding to gp130 which is present on all cells. Here we aimed to estimate the associations of these two pathways with risk of cardiovascular disease (CVD).Methods: IL-6 and sIL-6R were analyzed using the proximity extension assay. Baseline plasma samples were obtained from participants in the prospective Malmö Diet and Cancer (MDC) study (n = 4661), the SUMMIT VIP study (n = 1438) and the Carotid Plaque Imaging Project (CPIP, n = 285). Incident clinical events were obtained through national registers. Plaques removed at surgery were analyzed by immunohistochemistry and biochemical methods.Results: During 23.1 ± 7.0 years follow-up, 575 subjects in the MDC cohort suffered a first myocardial infarction. Subjects in the highest tertile of IL-6 had an increased risk compared to the lowest tertile (HR and 95% CI 2.60 [2.08-3.25]). High plasma IL-6 was also associated with more atherosclerosis, increased arterial stiffness, and impaired endothelial function in SUMMIT VIP, but IL-6 was only weakly associated with plaque inflammation in CPIP. sIL-6R showed no independent association with risk of myocardial infarction, atherosclerosis severity or vascular function, but was associated with plaque inflammation.Conclusions: Our findings show that sIL-6R is a poor marker of CVD risk and associated vascular changes. However, the observation that sIL-6R reflects plaque inflammation highlights the complexity of the role of IL-6 in CVD.</p

Soluble CD40 levels in plasma are associated with cardiovascular disease and in carotid plaques with a vulnerable phenotype

Background and Purpose CD40 and CD40 ligand (CD40L) are costimulatory molecules of the tumor necrosis factor receptor superfamily and well known for their involvement in inflammatory diseases: atherosclerotic mouse models with disrupted CD40 signalling develop lesions of reduced size with a more stable plaque profile. This study investigated the potential of plasma and intraplaque levels of CD40 and CD40L as markers for cardiovascular disease (CVD) in humans and their association with plaque stability. Methods Soluble CD40 and CD40L (sCD40L) were measured in plasma in 1,437 subjects from The SUrrogate markers for Micro-and Macro-vascular hard endpoints for Innovative diabetes Tools (SUMMIT) cohort. Intra-plaque levels of sCD40 and sCD40L were measured in atherosclerotic plaque homogenates from 199 subjects of the Carotid Plaque Imaging Project (CPIP) cohort. Results Both plasma sCD40 and sCD40L levels were elevated in individuals with prevalent stroke, while sCD40 levels also were higher in individuals with a prior acute myocardial infarction. Plasma levels of sCD40 correlated with carotid intima-media thickness and total carotid plaque area and were associated with risk of cardiovascular events over a 3-year follow-up period. Intra-plaque levels of sCD40 and sCD40L were associated with plaque components characteristic for plaque vulnerability and extracellular matrix remodelling. Conclusions Higher plasma sCD40 and sCD40L levels are associated with prevalent CVD. Plasma sCD40 levels also correlate with the severity of carotid atherosclerosis and predict future cardiovascular events, while intra-plaque levels correlate with a vulnerable plaque phenotype. Our findings thus demonstrate that elevated levels of sCD40 and sCD40L are markers of CVD.</p

24-h Glycaemic profiles in peritoneal dialysis patients and non-dialysis controls with advanced kidney disease

Background: For patients on peritoneal dialysis (PD), the deleterious effects of high concentrations of dialysate glucose on the peritoneal membrane are well-documented. Systemic effects of peritoneally absorbed glucose are more poorly defined. Using continuous glucose monitoring (CGM), we aimed to describe 24-h glycaemic profiles of PD patients without diabetes and compare with non-dialysis controls with stage 5 chronic kidney disease (CKD-5). Methods: In this cross-sectional, case-control study, 15 patients on PD (9 automated PD (APD) and 6 continuous ambulatory PD (CAPD)) and 16 CKD-5 controls underwent 72 h of CGM and metabolic profiling. CGM was used to derive average glucose concentrations and within-participant standard deviation (SD) of glucose. Data were analysed for the whole 72-h monitoring period and as daytime (09.00 to 21.00) and night-time (21.00 to 09.00). Results: Average glucose concentrations and within-participant SD of glucose for the whole monitoring period were not different between the three groups (p ≥ 0.5). Daytime average glucose concentrations were also similar across the three groups (p = 0.729). APD was associated with a significantly higher nocturnal glucose than CAPD (5.25 mmol/L ± 0.65 vs. 4.28 ± 0.5, p = 0.026). A significant drop in nocturnal glucose compared with daytime average seen in both CAPD patients and controls was absent in APD patients. Conclusions: Systematically different glycaemic patterns were observed in non-diabetic APD and CAPD patients, including an absence of physiological nocturnal glucose dipping in patients on APD. Comprehensive CGM data sets highlight subtleties not appreciated by traditional metabolic biomarkers; this has implications when choosing the most appropriate outcome measures in future research addressing the metabolic impact of PD

An exploratory study of the relationship between systemic microcirculatory function and small solute transport in incident peritoneal dialysis patients

Background: The peritoneal capillary endothelium is widely considered to be the most influential structure in dictating the rate of small solute transport (SST) during peritoneal dialysis (PD). PD patients are at significant risk of systemic microcirculatory dysfunction. The relationship between peritoneal and systemic microcirculations in patients new to PD has not been well studied. We hypothesised that for patients on PD for less than 6 months, dysfunction in the systemic microcirculation would be reflected in the rate of SST. Methods: We recruited 29 patients to a cross-sectional, observational study. Rate of SST was measured using a standard peritoneal equilibration test. Laser Doppler Flowmetry was used to measure response to physical and pharmacological challenge (post-occlusive hyperaemic response and iontophoretic application of vasodilators) in the cutaneous microcirculation. Sidestream Darkfield imaging was used to assess sublingual microvascular density, flow and endothelial barrier properties. Results: We found no moderate or strong correlations between any of the measures of systemic microcirculatory function and rate of SST or albumin clearance. There was however a significant correlation between dialysate interleukin-6 concentrations and both SST (rs = 0.758 p ≤ 0.0001) and albumin clearance (rs = 0.53, p = 0.01). Conclusions: In this study, systemic microvascular dysfunction did not significantly influence the rate of SST even early in patients PD careers. In conclusion, this study demonstrates that intraperitoneal factors particularly inflammation have a far greater impact on rate of SST than systemic factors