Safety and efficacy of abciximab in older adults undergoing percutaneous coronary intervention.

BACKGROUND: As a result of increased cost and bleeding concerns, older patients receive abciximab during percutaneous coronary intervention (PCI) less often than younger patients. OBJECTIVE: The aim of this was to evaluate the safety and efficacy of abciximab in older adults undergoing PCI. DESIGN: Retrospective, observational single centre cohort study. METHODS: The British Cardiovascular Intervention Society (BCIS) database was used to establish the impact of abciximab in people with advanced age (≥ 75 years) on in-hospital bleeding and ischaemic events and all-cause mortality in 5727 consecutive patients undergoing PCI between January 2008 and June 2014. RESULTS: Older patients represented 23% of the study population (n = 1298). Abciximab was used in 198 (15%) older patients and 970 (22%) younger patients (p < 0.001). Unadjusted bleeding and mortality rates were 1.2% and 5.6%, respectively, vs. 0.4% and 1.7% in younger patients (p = 0.001 and p < 0.001 respectively). On multivariate analysis older subjects were at higher risk of bleeding [odds ratio (OR) 2.76, 95% confidence interval (CI) 1.26-6.04, p = 0.011] and had higher in-hospital mortality (OR 2.36, 95% CI 1.48-3.74, p < 0.001). The use of abciximab in older patients was not significantly associated with excess bleeding (adjusted OR 1.86, 95% CI 0.58-5.93, p = 0.3), ischaemic outcomes (adjusted OR, 95% CI, p = 0.12) or in-hospital mortality (adjusted OR, 95% CI, p = 0.11). Older patients having primary PCI had higher risk of bleeding irrespective of abciximab use (adjusted p = 0.042). CONCLUSION: Abciximab may not be associated with excess bleeding complications in older patients compared with younger individuals and may be safe to use in older people if indicated.

Conjugatable water-soluble Pt(II) and Pd(II) porphyrin complexes: novel nano- and molecular probes for optical oxygen tension measurement in tissue engineering.

Measurement of oxygen tension in compressed collagen sheets was performed using matrix-embedded optical oxygen sensors based on platinum(II) and palladium(II) porphyrins supported on polyacrylamide nanoparticles. Bespoke, fully water-soluble, mono-functionalised Pt(II) and Pd(II) porphyrin complexes designed for conjugation under mild conditions were obtained using microwave-assisted metallation. The new sensors display a linear response (1/τ vs. O2) to varying oxygen tension over a biologically relevant range (7.0 × 10(-4) to 2.7 × 10(-1) mM) in aqueous solutions; a behaviour that is maintained following conjugation to polyacrylamide nanoparticles, and following embedding of the nanosensors in compressed collagen sheets, paving the way to innovative approaches for real-time resolution of oxygen gradients throughout 3D matrices useful for tissue regeneration.

Association between a functional polymorphism in Toll-like receptor 3 and chronic hepatitis C in liver transplant recipients.

BACKGROUND: Toll-like receptor 3 (TLR3) is implicated in the pathogenesis of viral diseases owing to its ability to recognize viral double-stranded RNA. We hypothesized that single nucleotide polymorphism (SNP) in TLR3 gene that impairs the function of the protein-receptor influences the outcome of hepatitis C virus (HCV) infection after liver transplantation. METHODS: The clinical characteristics of 611 liver recipients (HCV-infected: n = 153, non-HCV-infected: n = 458) were assessed to investigate the impact of TLR3 L412F SNP on transplant outcomes. RESULTS: TLR3 L412F is common, and it was significantly more prevalent among the HCV-infected cohort (57.5% vs. 45.2%, P = 0.008). In a multivariate analysis, TLR3 L412F was significantly associated with chronic hepatitis C (odds ratio: 1.73, 95% confidence interval [CI]: 1.13-2.65, P = 0.01). In an analysis that compared HCV-infected patients with wild-type versus TLR3 L412F, a marginally higher rate of allograft failure and mortality was observed in the TLR3 L412F group (44.3% vs. 30.8%, P = 0.09). However, in a multivariate analysis, only donor age was significantly associated with allograft failure and mortality (relative risk: 1.04, 95% CI: 1.007-1.06, P = 0.02). CONCLUSION: TLR3 L412F is significantly common in HCV-infected liver recipients, and may be associated with worse outcomes. However, larger studies are needed to determine its significant association with allograft failure and mortality after liver transplantation for chronic hepatitis C.

Dopamine D4 receptor gene variation moderates the efficacy of bupropion for smoking cessation.

Smokers (≥10 cigarettes per day, N=331) of European ancestry taking part in a double-blind placebo-controlled randomized trial of 12 weeks of treatment with bupropion along with counseling for smoking cessation were genotyped for a variable number of tandem repeats polymorphism in exon III of the dopamine D4 receptor gene. Generalized estimating equations predicting point-prevalence abstinence at end of treatment and 2, 6 and 12 months after the end of treatment indicated that bupropion (vs placebo) predicted increased odds of abstinence. The main effect of Genotype was not significant. A Genotype × Treatment interaction (P=0.005) showed that bupropion predicted increased odds of abstinence in long-allele carriers (odds ratios (OR)=1.31, P<0.0001), whereas bupropion was not associated with abstinence among short-allele homozygotes (OR=1.06, P=0.23). The Genotype × Treatment interaction remained when controlling for demographic and clinical covariates (P=0.01) and in analyses predicting continuous abstinence (P's≤0.054). Bupropion may be more efficacious for smokers who carry the long allele, which is relevant to personalized pharmacogenetic treatment approaches.

Engineering stable topography in dense bio-mimetic 3D collagen scaffolds.

Topographic features are well known to influence cell behaviour and can provide a powerful tool for engineering complex, functional tissues. This study aimed to investigate the mechanisms of formation of a stable micro-topography on plastic compressed (PC) collagen gels. The uni-directional fluid flow that accompanies PC of collagen gels creates a fluid leaving surface (FLS) and a non-fluid leaving surface (non-FLS). Here we tested the hypothesis that the resulting anisotropy in collagen density and stiffness between FLS and non-FLS would influence the fidelity and stability of micro-grooves patterned on these surfaces. A pattern template of parallel-aligned glass fibres was introduced to the FLS or non-FLS either at the start of the compression or halfway through, when a dense FLS had already formed. Results showed that both early and late patterning of the FLS generated grooves that had depth (25 ±7 µm and 19 ±8 µm, respectively) and width (55 ±11 µm and 50 ±12 µm, respectively) which matched the glass fibre diameter (50 µm). In contrast, early and late patterning of the non-FLS gave much wider (151 ±50 µm and 89 ±14 µm, respectively) and shallower (10 ±2.7 µm and 13 ±3.5 µm, respectively) grooves than expected. The depth to width ratio of the grooves generated on the FLS remained unaltered under static culture conditions over 2 weeks, indicating that grooves were stable under long term active cell-mediated matrix remodelling. These results indicate that the FLS, characterised by a higher matrix collagen density and stiffness than the non-FLS, provides the most favourable mechanical surface for precise engineering of a stable micro-topography in 3D collagen hydrogel scaffolds.

Effects of heparin and related drugs on neutrophil function.

We have previously demonstrated that heparin inhibits neutrophil activation, but the precise mechanism of action remains to be elucidated. The current aim was to further investigate the effects of heparin at inducing apoptosis of neutrophils and whether this was related to antagonism at IP(3) receptors. Furthermore, we investigated the ability of heparin and related molecules to inhibit acute neutrophil-induced injury to human bronchial epithelial cells (HBECs) in vitro. Neutrophils were isolated from human peripheral venous blood. Expression of annexin-V was determined in neutrophils following incubation with LMWH. The effects of LMWH and related molecules upon thapsigargin or m-3M3FBS (phospholipase C activator) induced neutrophil elastase (NE) release were also investigated. The cytotoxic effects of fMLP-activated neutrophils following co-incubation with HBECs were quantified through counting adherent cells before and after incubation. There was no detectable increase in annexin-V positive neutrophils following pre-incubation with LMWH at 30 min, 60 min or 16 h, but an increase was observed with Fas-activating antibody at 16 h. LMWH significantly inhibited NE release induced by either m-3M3FBS (73.4 ± 6.1%, 100 IU ml(-1), P < 0.01) or thapsigargin (62.4 ± 6.9%, 100 IU ml(-1), P < 0.01) in a sulphate-dependent manner. LMWH and related sulphated molecules all abrogated the cytotoxic effects of fMLP-activated neutrophils upon HBECs. In conclusion we were not able to demonstrate that heparin induces apoptosis and we did not find any evidence for heparin acting as an IP(3) receptor antagonist in neutrophils. Nonetheless, the potent inhibitory effects of heparin and related molecules upon neutrophil-induced injury to HBECs provide further evidence of the therapeutic potential of heparin and related molecules in the treatment of chronic inflammatory diseases.

Chromosomally integrated human herpesvirus-6 in transplant recipients.

Human herpesvirus-6 (HHV-6) is unique among human herpesviruses because of its ability to integrate into chromosomes. This entity, termed chromosomally integrated HHV-6 (CIHHV-6), is often mistaken for active infection and treated unnecessarily. The clinical significance of CIHHV-6 in transplant recipients is not defined. Herein, the clinical characteristics of 7 liver transplant patients with CIHHV-6 from our recent study, together with 14 other published cases of CIHHV-6 were reviewed. Of the 21 cases, CIHHV-6B was reported most commonly among solid organ transplant recipients, while CIHHV-6A was mostly seen in allogeneic hematopoietic stem cell recipients. None of the 21 patients developed clinical symptoms related to HHV-6 after transplantation. However, antiviral therapy was administered to 5 asymptomatic patients mistaken to have HHV-6 infection because of their very high HHV-6 DNA levels, 3 who developed symptomatic cytomegalovirus disease, and 1 with graft-versus-host disease that was mistaken for HHV-6 infection. In patients who received antiviral therapy, there was no apparent decline in HHV-6 DNA load, although change in viral kinetics is difficult to discern in the setting of high baseline HHV-6 DNA load. Clinicians should be aware of this entity of CIHHV-6 so that antiviral therapy can be considered in the proper clinical context.

Music preferences and personality among Japanese university students.

Little research has been conducted outside of the European-North American cultural area concerning the personality-based determinants of musical genre preferences The present research investigated the personality profiles and general music genre preferences of 268 Japanese college students. Six dimensions and 24 facets of personality, and 12 music genres, were assessed. Results indicated that, consistent with much previous research, openness (to experience) and particularly the facet of "aesthetic appreciation" were associated with a preference for "reflective" music (jazz, classical, opera, gospel, enka), while one extraversion facet (sociability) was associated with the preference for pop music. Other personality dimensions were less consistently associated with musical preferences, pointing to cultural differences and the need to assess both personality and music genres at more specific levels.

A clinical follow-up study of reserve forces personnel treated for mental health problems following demobilisation.

BACKGROUND: The Reserves Mental Health Programme (RMHP) provides a clinical service for members of the United Kingdom's Reserve Forces deployed to combat operations since 2003. AIM: To assess whether mental health and occupational functioning changed after treatment. METHODS: We examined a treatment group with operationally attributable mental health problems and a non-intervention group with non-operationally attributable problems. A self-report, repeat measures study design examined post traumatic stress disorder (PTSD), common mental disorders, alcohol use and occupational functioning at follow up delivered by either telephone or post. RESULTS: One hundred three reservists were offered an initial assessment. Adjusted response rates were 66.7% (n=16) for the no treatment group and 62.7% (n=37) for the treatment group. The treatment group were more likely to be cases at baseline on all mental health outcome measures other than PTSD, but at follow up, they were no more likely to be so. A one-way ANCOVA was conducted to evaluate treatment outcome. This was not significant for all measures except for PTSD. On completion of treatment, three quarters of serving personnel returned to full occupational fitness. CONCLUSION: The RMHP appears to offer a clinically and occupationally effective intervention to recently de-mobilised reservists with operationally attributable mental health problems.

Switching off angiogenic signalling: creating channelled constructs for adequate oxygen delivery in tissue engineered constructs.

A major question in biomimetic tissue engineering is how much of the structure/function of native vasculature needs to be reproduced for effective tissue perfusion. O2 supplied to cells in 3D scaffolds in vitro is initially dependent upon diffusion through the scaffold and cell consumption. Low O2 (3%) enhances specific cell behaviours, but where O2 is critically low (pathological hypoxia) cell survival becomes compromised. We measured real-time O2 in 3D scaffolds and introduced micro-channelled architecture to controllably increase delivery of O2 to cells and switch off the hypoxic response. Simple static micro-channelling gives adequate perfusion and can be used to control cell generated hypoxia-induced signalling.

Report from the 67th annual meeting of the American Academy of Dermatology.

The 67th Annual Meeting of the American Academy of Dermatology took place in San Francisco on 6-10 March 2009. The flavour of this busy but well-organized convention was a mixture of practical, hands-on teaching sessions, led and delivered by experts, with breakthrough cutting-edge scientific sessions. Aesthetic dermatology comprised a significant part of the meeting. It is impossible to encompass all the important presentations made at the meeting and satellite symposiums, but we highlight here a few medical pearls on dermoscopy, melanoma and oncology, inflammatory dermatoses and community-acquired methicillin-resistant Staphylococcus aureus. Our report is not intended as a substitute for reading the conference proceedings, educational session handouts, online updates and related references quoted in this article.

Neurotrophin-3-enhanced nerve regeneration selectively improves recovery of muscle fibers expressing myosin heavy chains 2b.

The purpose of this study was to evaluate the effect of neurotrophin 3 (NT-3) enhanced nerve regeneration on the reinnervation of a target muscle. Muscle fibers can be classified according to their mechanical properties and myosin heavy chain (MHC) isoform composition. MHC1 containing slow-type and MHC2a or 2b fast-type fibers are normally distributed in a mosaic pattern, their phenotype dictated by motor innervation. After denervation, all fibers switch to fast-type MHC2b expression and also undergo atrophy resulting in loss of muscle mass. After regeneration, discrimination between fast and slow fibers returns, but the distribution and fiber size change according to the level of reinnervation. In this study, rat gastrocnemius muscles (ipsilateral and contralateral to the side of nerve injury) were collected up to 8 mo after nerve repair, with or without local delivery of NT-3. The phenotype changes of MHC1, 2a, and 2b were analyzed by immunohistochemistry, and fiber type proportion, diameter, and grouping were assessed by computerized image analysis. At 8 mo, the local delivery of NT-3 resulted in significant improvement in gastrocnemius muscle weight compared with controls (NT-3 group 47%, controls 39% weight of contralateral normal muscle; P < 0.05). NT-3 delivery resulted in a significant increase in the proportion (NT-3 43.3%, controls 35.7%; P < 0.05) and diameter (NT-3 87.8 micron, controls 70.8 micron; P < 0.05) of fast type 2b fibers after reinnervation. This effect was specific to type 2b fibers; no normalization was seen in other fiber types. This study indicates that NT-3-enhanced axonal regeneration has a beneficial effect on the motor target organ. Also, NT-3 may be specifically affecting a subset of motoneurons that determine type 2b muscle fiber phenotype. As NT-3 was topically applied to cut nerves, our data suggest a discriminating effect of the neurotrophin on neuro-muscular interaction. These results would imply that muscle fibers may be differentially responsive to other neurotrophic factors and indicate the potential clinical role of NT-3 in the prevention of muscle atrophy after nerve injury.

Atomic clouds as distributed sources for the io plasma torus.

Several recent developments have implications for the neutral particle environment of Jupiter. Very hot sulfur ions have been detected in the Io torus with gyrospeeds comparable to the corotation speed, a phenomenon that would result from a neutral sulfur cloud. Current evidence supports the hypothesis that extensive neutral clouds of oxygen and sulfur exist in the Jupiter magnetosphere and that they are important sources of ions and energy for the Io torus.

Grazing by the Echinoid Diadema antillarum Philippi: Formation of Halos around West Indian Patch Reefs.

Between patch reefs and marine grass communities there is normally a zone or "halo" of heavily grazed grass 2 to 10 meters wide. Grazing by the echinoid Diadema antillarum Philippi during nocturnal migrations off the reefs is found to be the major factor in the formation of halos.

Hydrocarbons in open ocean waters.

Nonvolatile hydrocarbons in Atlantic Ocean and nearby waters were found to contain aromatics at lower concentrations than would be expected if the source of the hydrocarbons were crude oil or petroleum refinery products. Hydrocarbons appear to persist in the water to varying degrees with the most persistent being the cycloparaffins, then the isoparaffins, and finally the aromatics.

Surface observations for the evaluation of geophysical measurements from seasat.

The surface observations used in the initial assessment of Seasat are discussed with emphasis on their ability to describe the synoptic-scale winds over the ocean.

Seasat scatterometer: results of the gulf of alaska workshop.

The Seasat microwave scatterometer was designed to measure, globally and in nearly all weather, wind speed to an accuracy of +/- 2 meters per second and wind direction to +/- 20 degrees in two swaths 500 kilometers wide on either side of the spacecraft. For two operating modes in rain-free conditions, a limited number of comparisons to high-quality surface truth indicates that these specifications may have been met.