A prevalent mutation with founder effect in Spanish Recessive Dystrophic Epidermolysis Bullosa families

<p>Abstract</p> <p>Background</p> <p>Recessive Dystrophic Epidermolysis Bullosa (RDEB) is a genodermatosis caused by more than 500 different mutations in the <it>COL7A1 </it>gene and characterized by blistering of the skin following a minimal friction or mechanical trauma.</p> <p>The identification of a cluster of RDEB pedigrees carrying the c.6527insC mutation in a specific area raises the question of the origin of this mutation from a common ancestor or as a result of a hotspot mutation. The aim of this study was to investigate the origin of the c.6527insC mutation.</p> <p>Methods</p> <p>Haplotypes were constructed by genotyping nine single nucleotides polymorphisms (SNPs) throughout the <it>COL7A1 </it>gene. Haplotypes were determined in RDEB patients and control samples, both of Spanish origin.</p> <p>Results</p> <p>Sixteen different haplotypes were identified in our study. A single haplotype cosegregated with the c.6527insC mutation.</p> <p>Conclusion</p> <p>Haplotype analysis showed that all alleles carrying the c.6527insC mutation shared the same haplotype cosegregating with this mutation (<b><it>CCGCTCAAA_6527insC</it></b>), thus suggesting the presence of a common ancestor.</p

Functional assessment of coronary artery flow using adenosine stress dual-energy CT: a preliminary study

We attempted to assess coronary artery flow using adenosine-stress and dual-energy mode with dual-source CT (DE-CT). Data of 18 patients with suspected coronary arteries disease who had undergone cardiac DE-CT were retrospectively analyzed. The patients were divided into two groups: 10 patients who performed adenosine stress CT, and 8 patients who performed rest CT as controls. We reconstructed an iodine map and composite images at 120 kV (120 kV images) using raw data with scan parameters of 100 and 140 kV. We measured mean attenuation in the coronary artery proximal to the distal portion on both the iodine map and 120 kV images. Coronary enhancement ratio (CER) was calculated by dividing mean attenuation in the coronary artery by attenuation in the aortic root, and was used as an estimate of coronary enhancement. Coronary stenosis was identified as a reduction in diameter of >50% on CT angiogram, and myocardial ischemia was diagnosed by adenosine-stress myocardial perfusion scintigraphy. The iodine map showed that CER was significantly lower for ischemic territories (0.76 ± 0.06) or stenosed coronary arteries (0.77 ± 0.06) than for non-ischemic territories (0.95 ± 0.21, P = 0.02) or non-stenosed coronary arteries (1.07 ± 0.33, P < 0.001). The 120 kV images showed no difference in CER between these two groups. Use of CER on the iodine map separated ischemic territories from non-ischemic territories with a sensitivity of 86% and a specificity of 75%. Our quantification is the first non-invasive analytical technique for assessment of coronary artery flow using cardiac CT. CER on the iodine map is a candidate method for demonstration of alteration in coronary artery flow under adenosine stress, which is related to the physiological significance of coronary artery disease

A curriculum to teach medical students to care for people with disabilities: development and initial implementation

<p>Abstract</p> <p>Background</p> <p>Lack of knowledge and skills, and negative attitudes towards patients with disabilities, may adversely affect the services available to this group and negatively affect their health outcomes. The objective of this paper is to describe the development and initial implementation of a curriculum for teaching medical students to care for patients with disabilities.</p> <p>Methods</p> <p>We followed the six-step approach for developing curricula for medical education: general needs assessment, specific needs assessment, defining goals and objectives, determining the educational strategies, planning the implementation, and developing an evaluation plan.</p> <p>Results</p> <p>The curriculum has well defined goals and objectives covering knowledge, attitudes and skills. It employs both traditional and non-traditional teaching strategies. The implementation is planned over the four-year medical school curriculum in collaboration with a number of academic departments and specialized community-based agencies. The curriculum evaluation includes an attitudinal survey which is administered using a controlled design (pre- and post- exposure to the curriculum). The initial implementation of the curriculum has been very successful.</p> <p>Conclusion</p> <p>We have developed a longitudinal curriculum to teach medical students to care for people with disabilities. A rigorous evaluation of the impact of the curriculum is needed.</p

Daily life stress and the cortisol awakening response : testing the anticipation hypothesis

Acknowledgments We thank Paul Stewart for his contribution to data collection and Dr Matthew Jones for programming the handheld computers. Author Contributions Conceived and designed the experiments: WS DJP. Performed the experiments: DJP. Analyzed the data: WS. Wrote the paper: WS DJP.Peer reviewedPublisher PD

Turbulent flow as a cause for underestimating coronary flow reserve measured by Doppler guide wire

BACKGROUND: Doppler-tipped coronary guide-wires (FW) are well-established tools in interventional cardiology to quantitatively analyze coronary blood flow. Doppler wires are used to measure the coronary flow velocity reserve (CFVR). The CFVR remains reduced in some patients despite anatomically successful coronary angioplasty. It was the aim of our study to test the influence of changes in flow profile on the validity of intra-coronary Doppler flow velocity measurements in vitro. It is still unclear whether turbulent flow in coronary arteries is of importance for physiologic studies in vivo. METHODS: We perfused glass pipes of defined inner diameters (1.5 – 5.5 mm) with heparinized blood in a pulsatile flow model. Laminar and turbulent flow profiles were achieved by varying the flow velocity. The average peak velocity (APV) was recorded using 0.014 inch FW. Flow velocity measurements were also performed in 75 patients during coronary angiography. Coronary hyperemia was induced by intra-coronary injection of adenosine. The APV maximum was taken for further analysis. The mean luminal diameter of the coronary artery at the region of flow velocity measurement was calculated by quantitative angiography in two orthogonal planes. RESULTS: In vitro, the measured APV multiplied with the luminal area revealed a significant correlation to the given perfusion volumes in all diameters under laminar flow conditions (r(2 )> 0.85). Above a critical Reynolds number of 500 – indicating turbulent flow – the volume calculation derived by FW velocity measurement underestimated the actual rate of perfusion by up to 22.5 % (13 ± 4.6 %). In vivo, the hyperemic APV was measured irrespectively of the inherent deviation towards lower velocities. In 15 of 75 patients (20%) the maximum APV exceeded the velocity of the critical Reynolds number determined by the in vitro experiments. CONCLUSION: Doppler guide wires are a valid tool for exact measurement of coronary flow velocity below a critical Reynolds number of 500. Reaching a coronary flow velocity above the velocity of the critical Reynolds number may result in an underestimation of the CFVR caused by turbulent flow. This underestimation of the flow velocity may reach up to 22.5 % compared to the actual volumetric flow. Cardiologists should consider this phenomena in at least 20 % of patients when measuring CFVR for clinical decision making

One year follow-up of patients with refractory angina pectoris treated with enhanced external counterpulsation

BACKGROUND: Enhanced external counterpulsation (EECP) is a non-invasive technique that has been shown to be effective in reducing both angina and myocardial ischemia in patients not responding to medical therapy and without revascularization alternatives. The aim of the present study was to assess the long-term outcome of EECP treatment at a Scandinavian centre, in relieving angina in patients with chronic refractory angina pectoris. METHODS: 55 patients were treated with EECP. Canadian cardiovascular society (CCS) class, antianginal medication and adverse clinical events were collected prior to EECP, at the end of the treatment, and at six and 12 months after EECP treatment. Clinical signs and symptoms were recorded. RESULTS: EECP treatment significantly improved the CCS class in 79 ± 6% of the patients with chronic angina pectoris (p < 0.001). The reduction in CCS angina class was seen in patients with CCS class III and IV and persisted 12 months after EECP treatment. There was no significant relief in angina in patients with CCS class II prior to EECP treatment. 73 ± 7% of the patients with a reduction in CCS class after EECP treatment improved one CCS class, and 22 ± 7% of the patients improved two CCS classes. The improvement of two CCS classes could progress over a six months period and tended to be more prominent in patients with CCS class IV. In accordance with the reduction in CCS classes there was a significant decrease in the weekly nitroglycerin usage (p < 0.05). CONCLUSION: The results from the present study show that EECP is a safe treatment for highly symptomatic patients with refractory angina. The beneficial effects were sustained during a 12-months follow-up period

Effects of reducing beta-lactam antibiotic pressure on intestinal colonization of antibiotic-resistant gram-negative bacteria

Background: We determined the effects of two antibiotic policies (predominance of either β-lactam antibiotics or fluroquinolones) on acquisition with third-generation cephalosporin-resistant Enterobacteriaceae (CRE) and fluoroquinolone-resistant CRE (FCRE) in two ICUs, with monitoring of other variables that may influence acquisition. Methods: After an 8-month baseline period, units were randomized to a predominant β-lactam antibiotic regimen (weekly cycling of ceftriaxone, amoxicillin-clavulanic acid and fluroquinolones) or a fluoroquinolone regimen for 3 months, with cross-over for another 3 months. Acquisition of CRE and FCRE was determined by microbiological surveillance. Results: During baseline, acquisition rates for CRE and FCRE were 14/1,000 and 2/1,000 patient days at risk, respectively. Cross-transmission of CRE accounted for ≤25% of acquisitions, and CRE acquisition was associated with the use of β-lactam antibiotics (amoxicillin-clavulanic acid in particular). As compared to baseline, β-lactam antibiotic use [in defined daily dose (DDD)/1,000 patient days] was reduced from 854 to 526 (-39%) and 555 (-35%) during both intervention periods. Fluoroquinolone use was increased from 150 and 129 DDD/1,000 patient days in baseline and the β-lactam period to 514 DDD/1,000 patient days (+243%) in the fluoroquinolone period. Reductions in β-lactam use were not associated with reduced CRE acquisition [adjusted HRs were 1.0 (95% CR: 0.5-2.2) and 1.1 (95% CI: 0.5-2.5) during both periods, respectively]. Increased use of fluoroquinolones was associated with increased acquisition of FCRE [adjusted HR 4.1 (95% CI: 1.4-11.9; p < 0.01]. Infection control variables remained comparable during all periods. Conclusion: A 35-39% reduction of β-lactam exposure was not associated with reduced acquisition of CRE, whereas a 243% increase of fluoroquinolone use increased acquisition of FCRE

Biogenesis and functions of bacterial S-layers.

The outer surface of many archaea and bacteria is coated with a proteinaceous surface layer (known as an S-layer), which is formed by the self-assembly of monomeric proteins into a regularly spaced, two-dimensional array. Bacteria possess dedicated pathways for the secretion and anchoring of the S-layer to the cell wall, and some Gram-positive species have large S-layer-associated gene families. S-layers have important roles in growth and survival, and their many functions include the maintenance of cell integrity, enzyme display and, in pathogens and commensals, interaction with the host and its immune system. In this Review, we discuss our current knowledge of S-layer and related proteins, including their structures, mechanisms of secretion and anchoring and their diverse functions