In vivo measurement of tissue oxygenation by time-resolved luminescence spectroscopy: advantageous properties of dichlorotris(1, 10-phenanthroline)-ruthenium(II) hydrate.

Measuring tissue oxygenation in vivo is of interest in fundamental biological as well as medical applications. One minimally invasive approach to assess the oxygen partial pressure in tissue (pO2) is to measure the oxygen-dependent luminescence lifetime of molecular probes. The relation between tissue pO2 and the probes' luminescence lifetime is governed by the Stern-Volmer equation. Unfortunately, virtually all oxygen-sensitive probes based on this principle induce some degree of phototoxicity. For that reason, we studied the oxygen sensitivity and phototoxicity of dichlorotris(1, 10-phenanthroline)-ruthenium(II) hydrate [Ru(Phen)] using a dedicated optical fiber-based, time-resolved spectrometer in the chicken embryo chorioallantoic membrane. We demonstrated that, after intravenous injection, Ru(Phen)'s luminescence lifetime presents an easily detectable pO2 dependence at a low drug dose (1 mg∕kg) and low fluence (120 mJ∕cm2 at 470 nm). The phototoxic threshold was found to be at 10 J∕cm2 with the same wavelength and drug dose, i.e., about two orders of magnitude larger than the fluence necessary to perform a pO2 measurement. Finally, an illustrative application of this pO2 measurement approach in a hypoxic tumor environment is presented.

Prognostic accuracy of cerebral blood flow measurement by perfusion computed tomography, at the time of emergency room admission, in acute stroke patients.

The purpose of this study was to determine the prognostic accuracy of perfusion computed tomography (CT), performed at the time of emergency room admission, in acute stroke patients. Accuracy was determined by comparison of perfusion CT with delayed magnetic resonance (MR) and by monitoring the evolution of each patient's clinical condition. Twenty-two acute stroke patients underwent perfusion CT covering four contiguous 10mm slices on admission, as well as delayed MR, performed after a median interval of 3 days after emergency room admission. Eight were treated with thrombolytic agents. Infarct size on the admission perfusion CT was compared with that on the delayed diffusion-weighted (DWI)-MR, chosen as the gold standard. Delayed magnetic resonance angiography and perfusion-weighted MR were used to detect recanalization. A potential recuperation ratio, defined as PRR = penumbra size/(penumbra size + infarct size) on the admission perfusion CT, was compared with the evolution in each patient's clinical condition, defined by the National Institutes of Health Stroke Scale (NIHSS). In the 8 cases with arterial recanalization, the size of the cerebral infarct on the delayed DWI-MR was larger than or equal to that of the infarct on the admission perfusion CT, but smaller than or equal to that of the ischemic lesion on the admission perfusion CT; and the observed improvement in the NIHSS correlated with the PRR (correlation coefficient = 0.833). In the 14 cases with persistent arterial occlusion, infarct size on the delayed DWI-MR correlated with ischemic lesion size on the admission perfusion CT (r = 0.958). In all 22 patients, the admission NIHSS correlated with the size of the ischemic area on the admission perfusion CT (r = 0.627). Based on these findings, we conclude that perfusion CT allows the accurate prediction of the final infarct size and the evaluation of clinical prognosis for acute stroke patients at the time of emergency evaluation. It may also provide information about the extent of the penumbra. Perfusion CT could therefore be a valuable tool in the early management of acute stroke patients.

Ultimate test bench for pediatric biventricular assist device based on artificial muscles.

Ventricular assist devices (VADs) are used in treatment for terminal heart failure or as a bridge to transplantation. We created biVAD using the artificial muscles (AMs) that supports both ventricles at the same time. We developed the test bench (TB) as the in vitro evaluating system to enable the measurement of performance. The biVAD exerts different pressure between left and right ventricle like the heart physiologically does. The heart model based on child's heart was constructed in silicone. This model was fitted with the biVAD. Two pipettes containing water with an ultrasonic sensor placed on top of each and attached to ventricles reproduced the preload and the after load of each ventricle by the real-time measurement of the fluid height variation proportionally to the exerted pressure. The LabVIEW software extrapolated the displaced volume and the pressure generated by each side of our biVAD. The development of a standardized protocol permitted the validation of the TB for in vitro evaluation, measurement of the performances of the AM biVAD herein, and reproducibility of data.

Urinary sphincter based on electronics and artificial muscles

Objectives: The AMS 800TM is the current artificial urinary sphincter (AUS) for incontinence due to intrinsic sphincter deficiency. Despite good clinical results, technical failures inherent to the hydraulic mechanism or urethral ischemic injury contribute to revisions up to 60%. We are developing an electronic AUS, called ARTUS to overcome the rigors of AMS. The objective of this study was to evaluate the technical efficacy and tissue tolerance of the ARTUS system in an animal model.Methods: The ARTUS is composed by three parts: the contractile unit, a series of rings and an integrated microprocessor. The contractile unit is made of Nitinol fibers. The rings are placed around the urethra to control the flow of urine by squeezing the urethra. They work in a sequential alternative mode and are controlled by a microprocessor. In the first phase a three-rings device was used while in the second phase a two-rings ARTUS was used. The device was implanted in 14 sheep divided in two groups of six and eight animals for study purpose. The first group aimed at bladder leak point pressure (BLPP) measurement and validation of the animal model; the second group aimed at verifying mid-term tissue tolerance by explants at twelve weeks. General animal tolerance was also evaluated.Results: The ARTUS system implantation was uneventful. When the system was activated, the BLPP was measured at 1.038±0.044 bar (mean±SD). Urethral tissue analysis did not show significant morphological changes. No infection and no sign of discomfort were noted in animals at 12 weeks.Conclusions: The ARTUS proved to be effective in continence achievement in this study. Histological results support our idea that a sequential alternative mode can avoid urethral atrophy and ischemia. Further technical developments are needed to verify long-term outcome and permit human use.

Direct in vivo measurement of glycine and the neurochemical profile in the rat medulla oblongata.

The medulla oblongata (MO) contains a high density of glycinergic synapses and a particularly high concentration of glycine. The aims of this study were to measure directly in vivo the neurochemical profile, including glycine, in MO using a spin-echo-based (1)H MRS sequence at TE?=?2.8 ms and to compare it with three other brain regions (cortex, striatum and hippocampus) in the rat. Glycine was quantified in MO at TE?=?2.8 ms with a Cramér-Rao lower bound (CRLB) of approximately 5%. As a result of the relatively low level of glycine in the other three regions, the measurement of glycine was performed at TE?=?20 ms, which provides a favorable J-modulation of overlapping myo-inositol resonance. The other 14 metabolites composing the neurochemical profile were quantified in vivo in MO with CRLBs below 25%. Absolute concentrations of metabolites in MO, such as glutamate, glutamine, ?-aminobutyrate, taurine and glycine, were in the range of previous in vitro quantifications in tissue extracts. Compared with the other regions, MO had a three-fold higher glycine concentration, and was characterised by reduced (p?<?0.001) concentrations of glutamate (-50?±?4%), glutamine (-54?±?3%) and taurine (-78?±?3%). This study suggests that the functional specialisation of distinct brain regions is reflected in the neurochemical profile.

The significance of pre-existing minority Y181C mutations on virological failure of NNRTI-based, first-line antiretroviral therapy

Background: Reduced re'nal function has been reported with tenofovir disoproxil fumarate (TDF). It is not clear whether TDF co-administered with a boosted protease inhibitor (PI) leads to a greater decline in renal function than TDF co-administered with a non-nucleoside reverse transcriptase inhibitor (NNRTI).Methods: We selected ail antiretroviral therapy-naive patients in the Swiss HIV Cohort Study (SHCS) with calibrated or corrected serum creatinine measurements starting antiretroviral therapy with TDF and either efavirenz (EFV) or the ritonavir-boosted PIs, lopinavir (LPV/r) or atazanavir (ATV/r). As a measure of renal function, we used the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation to estimate the glomerular filtration rate (eGFR). We calculated the difference in eGFR over time between two therapies using a marginal model for repeated measures. In weighted analyses, observations were weighted by the product of their point of treatment and censoring weights to adjust for differences both in the sort of patients starting each therapy and in the sort of patients remaining on each therapy over time.Results: By March 2011, 940 patients with at least one creatinine measurement on a first therapy with either TDF and EFV (n=484), TDF and LPVlr (n=269) or TDF and ATV/r (n=187) had been followed for a median of 1. 7, 1.2 and 1.3 years, respectively. Table 1 shows the difference in average estimated GFR (eGFR) over time since starting cART for two marginal models. The first model was not adjusted for potential confounders; the second mode! used weights to adjust for confounders. The results suggest a greater decline in renal function during the first 6 months if TDF is used with a PI rather than with an NNRTI, but no further difference between these therapies after the first 6 months. TDF and ATV/r may lead to a greater decline in the first 6 months than TDF and LPVlr.Conclusions: TDF co-administered with a boosted PI leads to a greater de cline in renal function over the first 6 months of therapy than TDF co-administered with an NNRTI; this decline may be worse with ATV/r than with LPV/r.

Could a satellite-based navigation system (GPS) be used to assess the physical activity of individuals on earth?

OBJECTIVES: To test whether the Global Positioning System (GPS) could be potentially useful to assess the velocity of walking and running in humans. SUBJECT: A young man was equipped with a GPS receptor while walking running and cycling at various velocity on an athletic track. The speed of displacement assessed by GPS, was compared to that directly measured by chronometry (76 tests). RESULTS: In walking and running conditions (from 2-20 km/h) as well as cycling conditions (from 20-40 km/h), there was a significant relationship between the speed assessed by GPS and that actually measured (r = 0.99, P < 0.0001) with little bias in the prediction of velocity. The overall error of prediction (s.d. of difference) averaged +/-0.8 km/h. CONCLUSION: The GPS technique appears very promising for speed assessment although the relative accuracy at walking speed is still insufficient for research purposes. It may be improved by using differential GPS measurement.

How to Measure Scope Variables when no Metrics Exist : Application to Landscape Quality Measurement and Hedonic Price Evaluation

Landscape is an example of a non-market good where no metrics exist to measure its quality. The paper proposes an original methodology to nevertheless estimate scope variables in those circumstances, allowing then to better test if people's willingnesstopay for such good is sensitive to the scope. The methodology is based on techniques developed in the context of multicriteria decision analysis. It is applied to assess the quality of the landscape of several Swiss alpine resorts. This assessment is then used as an explanatory variable in a hedonic price function to explain the rent of apartments and to derive an implicit price of the landscape quality.

Endoscopic low-coherence topography measurement for upper airways and hollow samples.

To evaluate the severity of airway pathologies, quantitative dimensioning of airways is of utmost importance. Endoscopic vision gives a projective image and thus no true scaling information can be directly deduced from it. In this article, an approach based on an interferometric setup, a low-coherence laser source and a standard rigid endoscope is presented, and applied to hollow samples measurements. More generally, the use of the low-coherence interferometric setup detailed here could be extended to any other endoscopy-related field of interest, e.g., gastroscopy, arthroscopy and other medical or industrial applications where tri-dimensional topology is required. The setup design with a multiple fibers illumination system is presented. Demonstration of the method ability to operate on biological samples is assessed through measurements on ex vivo pig bronchi.

The Lausanne cohort Lc65+: a population-based prospective study of the manifestations, determinants and outcomes of frailty

BACKGROUND: Frailty is a relatively new geriatric concept referring to an increased vulnerability to stressors. Various definitions have been proposed, as well as a range of multidimensional instruments for its measurement. More recently, a frailty phenotype that predicts a range of adverse outcomes has been described. Understanding frailty is a particular challenge both from a clinical and a public health perspective because it may be a reversible precursor of functional dependence. The Lausanne cohort Lc65+ is a longitudinal study specifically designed to investigate the manifestations of frailty from its first signs in the youngest old, identify medical and psychosocial determinants, and describe its evolution and related outcomes. METHODS/DESIGN: The Lc65+ cohort was launched in 2004 with the random selection of 3054 eligible individuals aged 65 to 70 (birth year 1934-1938) in the non-institutionalized population of Lausanne (Switzerland). The baseline data collection was completed among 1422 participants in 2004-2005 through questionnaires, examination and performance tests. It comprised a wide range of medical and psychosocial dimensions, including a life course history of adverse events. Outcomes measures comprise subjective health, limitations in activities of daily living, mobility impairments, development of medical conditions or chronic health problems, falls, institutionalization, health services utilization, and death. Two additional random samples of 65-70 years old subjects will be surveyed in 2009 (birth year 1939-1943) and in 2014 (birth year 1944-1948). DISCUSSION: The Lc65+ study focuses on the sequence "Determinants --> Components --> Consequences" of frailty. It currently provides information on health in the youngest old and will allow comparisons to be made between the profiles of aging individuals born before, during and at the end of the Second World War.

Blood pressure monitoring through pharmacies and team-based care of hypertension.

In the last issue of Blood Pressure Monitoring, (James K, Dolan E, O'Brien E. Making ambulatory blood pressure monitoring accessible in pharmacies. Blood Press Monit 2014;19:134-139) elegantly reported for the first time the characteristics of patients attending pharmacies for ambulatory blood pressure measurement (ABPM) and showed that they were similar to those undergoing ABPM through primary care practices. The authors concluded that pharmacies could be a valuable resource to perform ABPM. In the continuity of this study, we would like to emphasize the results of recent studies as well as recommenda-tions of pharmacist involvement in the management of hypertension, more specifically in a team approach.

Introducing a new MRI classification of lumbar spinal stenosis based on cross-sectional morphology of the dural sac : 37

Introduction: Measures of the degree of lumbar spinal stenosis (LSS) such as antero-posterior diameter of the canal, and dural sac cross sectional area vary, and do not correlate with symptoms or results of surgery. We created a grading system, comprised of seven categories, based on the morphology of the dural sac and its contents as seen on T2 axial images. The categories take into account the ratio of rootlet/ CSF content. Grade A indicates no significant compression, grade D is equivalent to a total myelograhic block. We compared this classification with commonly used criteria of severity of stenosis. Methods: Fifty T2 axial MRI images taken at disc level from 27 symptomatic LSS patients undergoing decompressive surgery were classified twice by two radiologists and three spinal surgeons working at different institutions and countries. Dural sac cross-sectional surface area and AP diameter of the canal were measured both at disc and pedicle level from DICOM images using OsiriX software. Intraand inter-observer reliability were assessed using Cohen's, Fleiss' kappa statistics, and t test. Results: For the morphological grading the average intra-and inter observer kappas were 0.76 and 0.69+, respectively, for physicians working in the study originating country. Combining all observers the kappa values were 0.57 ± 0.19. and 0.44 ± 0.19, respectively. AP diameter and dural sac cross-sectional area measurements showed no statistically significant differences between observers. No correlation between morphological grading and AP diameter or dural sac crosssectional areawas observed in 13 (26%) and 8 cases (16%), respectively. Discussion: The proposed morphological grading relies on the identification of the dural sac and CSF better seen on full MRI series. This was not available to the external observers, which might explain the lower overall kappa values. Since no specific measurement tools are needed the grading suits everyday clinical practice and favours communication of degree of stenosis between practising physicians. The absence of a strict correlation with the dural sac surface suggests that measuring the surface alone might be insufficient in defining LSS as it is essentially a mismatch between the spinal canal and its contents. This grading is now adopted in our unit and further studies concentrating on relation between morphology, clinical symptoms and surgical results are underway.

Usefulness of methadone plasma concentration measurement in patients receiving nevirapine or efavirenz.

Objective: To determine methadone plasma trough and peak concentrations in patients presenting opiate withdrawal symptoms after introduction of nevirapine or efavirenz. To describe the disappearance of these symptoms after methadone titration based on plasma concentrations rather than on the symptoms. Methods: Nine patients undergoing highly active antiretroviral therapy (HAART) and either nevirapine or efavirenz treatment were monitored daily for opiate withdrawal in a specialized drug addiction center. Methadone dose was titrated daily, and plasma concentrations were measured. The data are retrospective (case series). Results: Several patients complained of symptoms such as nausea, vomiting, accelerated intestinal transit, or insomnia. Even after methadone titration based on clinical symptoms, patients and health-care providers trained in infectious disease did not classify these as withdrawal symptoms and considered them as the side effects of HAART or anxiety. Methadone plasma trough concentration showed low levels of (R)- and (R,S)-methadone. Further methadone dose adjustment according to plasma level resulted in the disappearance of these withdrawal symptoms. The daily methadone dose was split when the peak/trough (R)-methadone ratio was more than 2. Conclusions: When introducing efavirenz or nevirapine to patients undergoing methadone treatment, withdrawal symptoms should be monitored, especially those such as insomnia, vomiting, or nausea. Methadone plasma trough and peak measurements can be of value in preventing unnecessary side effects of HAART.

Modelling the effect of minor orthopaedic day surgery on patient mood at the early post-operative period: a prospective population-based cohort study.

OBJECTIVE: The effect of minor orthopaedic day surgery (MiODS) on patient's mood. METHODS: A prospective population-based cohort study of 148 consecutive patients with age above 18 and less than 65, an American Society of Anaesthesiology (ASA) score of 1, and the requirement of general anaesthesia (GA) were included. The Medical Outcomes Study - Short Form 36 (SF-36), Beck Anxiety Inventory (BAI) and Beck Depression Inventory (BDI) were used pre- and post-operatively. RESULTS: The mean physical component score of SF-36 before surgery was 45.3 (SD=+/-10.1) and 8 weeks following surgery was 44.9 (SD=+/-11.04) [n=148, p=0.51, 95% CI=(-1.03 to 1.52)]. For the measurement of the changes in mood using BDI, BAI and SF-36, latent construct modelling was employed to increase validity. The covariance between mood pre- and post-operatively (cov=69.44) corresponded to a correlation coefficient, r=0.88 indicating that patients suffering a greater number of mood symptoms before surgery continue to have a greater number of symptoms following surgery. When the latent mood constructs were permitted to have different means the model fitted well with chi(2) (df=1)=0.86 for which p=0.77, thus the null hypothesis that MiODS has no effect on patient mood was rejected. CONCLUSIONS: MiODS affects patient mood which deteriorates at 8 weeks post-operatively regardless of the pre-operative patient mood state. More importantly patients suffering a greater number of mood symptoms before MiODS continue to have a greater number of symptoms following surgery.

How are "teaching the teachers" courses in evidence based medicine evaluated? A systematic review.

BACKGROUND: Teaching of evidence-based medicine (EBM) has become widespread in medical education. Teaching the teachers (TTT) courses address the increased teaching demand and the need to improve effectiveness of EBM teaching. We conducted a systematic review of assessment tools for EBM TTT courses.To summarise and appraise existing assessment methods for teaching the teachers courses in EBM by a systematic review. METHODS: We searched PubMed, BioMed, EmBase, Cochrane and Eric databases without language restrictions and included articles that assessed its participants. Study selection and data extraction were conducted independently by two reviewers. RESULTS: Of 1230 potentially relevant studies, five papers met the selection criteria. There were no specific assessment tools for evaluating effectiveness of EBM TTT courses. Some of the material available might be useful in initiating the development of such an assessment tool. CONCLUSION: There is a need for the development of educationally sound assessment tools for teaching the teachers courses in EBM, without which it would be impossible to ascertain if such courses have the desired effect.