L-canavanine, an inhibitor of inducible nitric oxide synthase, improves venous return in endotoxemic rats.

OBJECTIVE: To investigate the hemodynamic effects of L-canavanine (an inhibitor of inducible, but not of constitutive, nitric oxide synthase) in endotoxic shock. DESIGN: Controlled, randomized, experimental study. SETTING: Animal laboratory. SUBJECTS: Wistar rats. INTERVENTIONS: Rats were anesthetized with pentobarbital, and hemodynamically monitored. One hour after an intravenous challenge with 5 mg/kg of Escherichia coli endotoxin, the rats were randomized to receive a continuous infusion of either L-canavanine (20 mg/kg/hr; n = 8) or vehicle only (isotonic saline, n = 11). In all animals, the infusion was given over 5 hrs at a rate of 2 mL/kg/hr. These experiments were repeated in additional rats challenged with isotonic saline instead of endotoxin (sham experiments). MEASUREMENTS AND MAIN RESULTS: Arterial blood pressure, heart rate, thermodilution cardiac output, central venous pressure, mean systemic filling pressure, urine output, arterial blood gases, blood lactate concentration, and hematocrit were measured. In sham experiments, hemodynamic stability was maintained throughout and L-canavanine had no detectable effect. Animals challenged with endotoxin and not treated with L-canavanine developed progressive hypotension and low cardiac output. After 6 hrs of endotoxemia, both central venous pressure and mean systemic filling pressure were significantly below their baseline values, indicating relative hypovolemia as the main determinant of reduced cardiac output. In endotoxemic animals treated with L-canavanine, hypotension was less marked, while cardiac output, central venous pressure, and mean systemic filling pressure were maintained throughout the experiment. L-canavanine had no effect on the time-course of hematocrit. L-canavanine significantly increased urine output and reduced the severity of lactic acidosis. CONCLUSIONS: Six hours after an endotoxin challenge in rats, low cardiac output develops, which appears to be primarily related to relative hypovolemia. L-canavanine, a selective inhibitor of the inducible nitric oxide synthase, increases the mean systemic filling pressure, thereby improving venous return, under these conditions.

Automatic low baseline stereo in urban areas

In this work we propose a new automatic methodology for computing accurate digital elevation models (DEMs) in urban environments from low baseline stereo pairs that shall be available in the future from a new kind of earth observation satellite. This setting makes both views of the scene similarly, thus avoiding occlusions and illumination changes, which are the main disadvantages of the commonly accepted large-baseline configuration. There still remain two crucial technological challenges: (i) precisely estimating DEMs with strong discontinuities and (ii) providing a statistically proven result, automatically. The first one is solved here by a piecewise affine representation that is well adapted to man-made landscapes, whereas the application of computational Gestalt theory introduces reliability and automation. In fact this theory allows us to reduce the number of parameters to be adjusted, and tocontrol the number of false detections. This leads to the selection of a suitable segmentation into affine regions (whenever possible) by a novel and completely automatic perceptual grouping method. It also allows us to discriminate e.g. vegetation-dominated regions, where such an affine model does not apply anda more classical correlation technique should be preferred. In addition we propose here an extension of the classical ”quantized” Gestalt theory to continuous measurements, thus combining its reliability with the precision of variational robust estimation and fine interpolation methods that are necessary in the low baseline case. Such an extension is very general and will be useful for many other applications as well.

Interobserver and intraobserver variability of the apparent diffusion coefficient in treated malignant hepatic lesions on a 3.0T machine: measurements in the whole lesion versus in the area with the most restricted diffusion.

PURPOSE: To assess the inter/intraobserver variability of apparent diffusion coefficient (ADC) measurements in treated hepatic lesions and to compare ADC measurements in the whole lesion and in the area with the most restricted diffusion (MRDA). MATERIALS AND METHODS: Twenty-five patients with treated malignant liver lesions were examined on a 3.0T machine. After agreeing on the best ADC image, two readers independently measured the ADC values in the whole lesion and in the MRDA. These measurements were repeated 1 month later. The Bland-Altman method, Spearman correlation coefficients, and the Wilcoxon signed-rank test were used to evaluate the measurements. RESULTS: Interobserver variability for ADC measurements in the whole lesion and in the MRDA was 0.17 x 10(-3) mm(2)/s [-0.17, +0.17] and 0.43 x 10(-3) mm(2)/s [-0.45, +0.41], respectively. Intraobserver limits of agreement could be as low as [-0.10, +0.12] 10(-3) mm(2)/s and [-0.20, +0.33] 10(-3) mm(2)/s for measurements in the whole lesion and in the MRDA, respectively. CONCLUSION: A limited variability in ADC measurements does exist, and it should be considered when interpreting ADC values of hepatic malignancies. This is especially true for the measurements of the minimal ADC.

Variability of radioiodine measurements in the thyroid.

Monte Carlo simulations were carried out to study the response of a thyroid monitor for measuring intake activities of (125)I and (131)I. The aim of the study was 3-fold: to cross-validate the Monte Carlo simulation programs, to study the response of the detector using different phantoms and to study the effects of anatomical variations. Simulations were performed using the Swiss reference phantom and several voxelised phantoms. Determining the position of the thyroid is crucial for an accurate determination of radiological risks. The detector response using the Swiss reference phantom was in fairly good agreement with the response obtained using adult voxelised phantoms for (131)I, but should be revised for a better calibration for (125)I and for any measurements taken on paediatric patients.

Relay card for capacitance measurements

In this bachelor's thesis a relay card for capacitance measurements was designed, built and tested. The study was made for the research and development laboratory of VTI Technologies, which manufactures capacitive silicon micro electro mechanical accelerometers and pressure sensors. As the size of the sensors is decreasing the capacitance value of the sensors also decreases. The decreased capacitance causes a need for new and more accurate measurement systems. The technology used in the instrument measuring the capacitance dictates a framework how the relay card should be designed, thus the operating principle of the instrument must be known. To achieve accurate results the measurement instrument and its functions needed to be used correctly. The relay card was designed using printed circuit board design methods that minimize interference coupling to the measurement. The relay card that was designed in this study is modular. It consists of a separate CPU card, which was used to control the add-on cards connected to it. The CPU card was controlled from a computer through a serial bus. Two add-on cards for the CPU card were designed in this study. The first one was the measurement card, which could be used to measure 32 capacitive sensors. The second add-on card was the MUX card, which could be used to switch between two measurement cards. The capacitance measurements carried out through the MUX card and the measurement cards were characterized with a series of test measurements. The test measurement data was then analysed. The relay card design was confirmed to work and offer accurate measurement results up to a measurement frequency of 10 MHz. The length of the measurement cables limited the measurement frequency.

Improving social measurements: the experience of the ESS first rounds in Spain

With the two aims of monitoring social change and improving social measurement, the European Social Survey is now closing its third round. This paper shows how the accumulated experience of the two first rounds has been used to validate the questionnaire, better adapt the sampling design to the country characteristics and efficiently commit fieldwork in Spain. For example, the dynamic character of the population nowadays makes necessary to estimated design effects at each round from the data of the previous round. The paper also demonstrates how, starting with a response rate of 52% at first round, a 66% response rate is achieved at the third round thanks to an extensive quality control conducted by the polling agency and the ESS national team and based on a detailed analysis of the non-response cases and the incidences reported by the interviewed in the contact form.

Low estimates of dietary acid load are positively associated with bone ultrasound in women older than 75 years of age with a lifetime fracture

Dietary acid load from Western diets may be a risk factor for osteoporosis. It can be estimated by net endogenous acid production (NEAP). No data currently exists for NEAP estimates and bone indices in the very elderly (i.e. > or = 75 y). The aim of this study was to determine the association between NEAP estimates by using the potential renal acid load (PRAL) equation and quantitative bone ultrasound (QUS) measurements at the heel [broadband ultrasound attenuation (BUA)] in Caucasian women. We assessed NEAP and QUS in 401 very elderly Swiss ambulatory women. We evaluated dietary intake and NEAP estimates with a validated FFQ. QUS was measured using Achilles (Lunar). We identified 2 subgroups: 256 women (80.6 y +/- 3; BUA, 96.8 dB/MHz) with a fracture history and the remaining 145 (79.9 y SD 2.9; BUA, 101.7 dB/MHz) without. Women who reported having suffered a fracture had lower BUA (P < 0.001) than nonfractured women but did not differ in nutrient intakes and NEAP. Lower NEAP (P = 0.023) and higher potassium intake (P = 0.033) were correlated with higher BUA, which remained significant even after adjustment for age, BMI, and osteoporosis treatment. BUA was positively correlated with calcium (P = 0.016) and BMI (P < 0.001). Women who reported no fractures had no significant correlations between nutrient intake, NEAP, and BUA. Low nutritional acid load was correlated with higher BUA in very elderly women with a fracture history. Although relatively weak compared with age and BMI, this association was significant and may be an important additional risk factor that might be particularly relevant in frail patients with an already high fracture risk.

Scalable inference of heterogeneous reaction kinetics from pooled single-cell recordings.

Mathematical methods combined with measurements of single-cell dynamics provide a means to reconstruct intracellular processes that are only partly or indirectly accessible experimentally. To obtain reliable reconstructions, the pooling of measurements from several cells of a clonal population is mandatory. However, cell-to-cell variability originating from diverse sources poses computational challenges for such process reconstruction. We introduce a scalable Bayesian inference framework that properly accounts for population heterogeneity. The method allows inference of inaccessible molecular states and kinetic parameters; computation of Bayes factors for model selection; and dissection of intrinsic, extrinsic and technical noise. We show how additional single-cell readouts such as morphological features can be included in the analysis. We use the method to reconstruct the expression dynamics of a gene under an inducible promoter in yeast from time-lapse microscopy data.

Opioid antagonist detoxification under anaesthesia versus traditional clonidine detoxification combined with an additional week of psychosocial support: a randomised clinical trial.

BACKGROUND: While detoxification under anaesthesia accelerates the detoxification procedure, there is a lack of randomised clinical trials evaluating its effectiveness compared to traditional detoxification procedures, and a lack of data on long-term abstinence. METHODS: Prospective randomised clinical trial. Analysis by intention to treat and per protocol. Setting: Specialised substance abuse unit in a psychiatric teaching hospital and an intensive care unit of a general hospital. Participants: Seventy patients with opiate mono-dependence requesting detoxification: 36 randomised to RODA (treatment as allocated received by 26) and 34 randomised to classical clonidine detoxification (treatment as allocated received by 21). Main outcome measures: Successful detoxification, safety and self-reported abstinence at 3, 6 and 12 months after detoxification. RESULTS: Socio-demographics were similar in both groups at baseline. No complications were reported during or after anaesthesia. According to the intention to treat analysis, 28/36 (78%) RODA patients and 21/34 (62%) of the clonidine group successfully completed the detoxification process (p=0.14). In the intention to treat analysis, 30% of RODA patients were abstinent after 3 months compared to 14% in the clonidine group (p=0.11). No difference was found at 6 and 12 months (both groups showed less than 5% abstinence after 12 months). The per-protocol analysis showed similar results with no statistical differences either for ASI mean scores or for the SF36 questionnaire. CONCLUSION: Although the detoxification success rate and abstinence after 3 months were slightly better for the RODA procedure compared to clonidine treatment, these differences were not statistically significant and disappeared completely after 6 and 12 months.

Measurements of three-dimensional glenoid erosion when planning the prosthetic replacement of osteoarthritic shoulders.

The three-dimensional (3D) correction of glenoid erosion is critical to the long-term success of total shoulder replacement (TSR). In order to characterise the 3D morphology of eroded glenoid surfaces, we looked for a set of morphological parameters useful for TSR planning. We defined a scapular coordinates system based on non-eroded bony landmarks. The maximum glenoid version was measured and specified in 3D by its orientation angle. Medialisation was considered relative to the spino-glenoid notch. We analysed regular CT scans of 19 normal (N) and 86 osteoarthritic (OA) scapulae. When the maximum version of OA shoulders was higher than 10°, the orientation was not only posterior, but extended in postero-superior (35%), postero-inferior (6%) and anterior sectors (4%). The medialisation of the glenoid was higher in OA than normal shoulders. The orientation angle of maximum version appeared as a critical parameter to specify the glenoid shape in 3D. It will be very useful in planning the best position for the glenoid in TSR.

Primary activity measurements with a 4πβ-4πγ coincidence counting system.

The radioactive concentrations of (166m)Ho, (134)Cs and (133)Ba solutions have been standardised using a 4πβ-4πγ coincidence counting system we have recently set up. The detection in the beta channel is performed using various geometries of a UPS-89 plastic scintillator optically coupled to a selected low-noise 1in. diameter photomultiplier tube. The light-tight thin capsule that encloses this beta detector is housed within the well of a 5in.×5in. NaI(Tl) monocrystal detector. The beta detection efficiency can be varied either by optical filtering or electronic discrimination when the electrons loose all their energy in the plastic scintillator. This 4πβ-4πγ coincidence system improves on our 4πβ(PC)-γ system in that its sample preparation is less labour intensive, it yields larger beta- and gamma-counting efficiencies thus enabling the standardisation of low activity sources with good statistics in reasonable time, and it makes standardising short-lived radionuclides easier. The resulting radioactive concentrations of (166m)Ho, (134)Cs and (133)Ba are found to agree with those measured with other primary measurement methods thus validating our 4πβ-4πγ coincidence counting system.

A validated assay for measuring doxorubicin in biological fluids and tissues in an isolated lung perfusion model: matrix effect and heparin interference strongly influence doxorubicin measurements.

Doxorubicin is an antineoplasic agent active against sarcoma pulmonary metastasis, but its clinical use is hampered by its myelotoxicity and its cumulative cardiotoxicity, when administered systemically. This limitation may be circumvented using the isolated lung perfusion (ILP) approach, wherein a therapeutic agent is infused locoregionally after vascular isolation of the lung. The influence of the mode of infusion (anterograde (AG): through the pulmonary artery (PA); retrograde (RG): through the pulmonary vein (PV)) on doxorubicin pharmacokinetics and lung distribution was unknown. Therefore, a simple, rapid and sensitive high-performance liquid chromatography method has been developed to quantify doxorubicin in four different biological matrices (infusion effluent, serum, tissues with low or high levels of doxorubicin). The related compound daunorubicin was used as internal standard (I.S.). Following a single-step protein precipitation of 500 microl samples with 250 microl acetone and 50 microl zinc sulfate 70% aqueous solution, the obtained supernatant was evaporated to dryness at 60 degrees C for exactly 45 min under a stream of nitrogen and the solid residue was solubilized in 200 microl of purified water. A 100 microl-volume was subjected to HPLC analysis onto a Nucleosil 100-5 microm C18 AB column equipped with a guard column (Nucleosil 100-5 microm C(6)H(5) (phenyl) end-capped) using a gradient elution of acetonitrile and 1-heptanesulfonic acid 0.2% pH 4: 15/85 at 0 min-->50/50 at 20 min-->100/0 at 22 min-->15/85 at 24 min-->15/85 at 26 min, delivered at 1 ml/min. The analytes were detected by fluorescence detection with excitation and emission wavelength set at 480 and 550 nm, respectively. The calibration curves were linear over the range of 2-1000 ng/ml for effluent and plasma matrices, and 0.1 microg/g-750 microg/g for tissues matrices. The method is precise with inter-day and intra-day relative standard deviation within 0.5 and 6.7% and accurate with inter-day and intra-day deviations between -5.4 and +7.7%. The in vitro stability in all matrices and in processed samples has been studied at -80 degrees C for 1 month, and at 4 degrees C for 48 h, respectively. During initial studies, heparin used as anticoagulant was found to profoundly influence the measurements of doxorubicin in effluents collected from animals under ILP. Moreover, the strong matrix effect observed with tissues samples indicate that it is mandatory to prepare doxorubicin calibration standard samples in biological matrices which would reflect at best the composition of samples to be analyzed. This method was successfully applied in animal studies for the analysis of effluent, serum and tissue samples collected from pigs and rats undergoing ILP.

Therapy modifications in response to poorly controlled hypertension, dyslipidemia, and diabetes mellitus.

BACKGROUND: Poorly controlled cardiovascular risk factors are common. Evaluating whether physicians respond appropriately to poor risk factor control in patients may better reflect quality of care than measuring proportions of patients whose conditions are controlled. OBJECTIVES: To evaluate therapy modifications in response to poor control of hypertension, dyslipidemia, or diabetes in a large clinical population. DESIGN: Retrospective cohort study within an 18-month period in 2002 to 2003. SETTING: Kaiser Permanente of Northern California. PATIENTS: 253,238 adult members with poor control of 1 or more of these conditions. MEASUREMENTS: The authors assessed the proportion of patients with poor control who experienced a change in pharmacotherapy within 6 months, and they defined "appropriate care" as a therapy modification or return to control without therapy modification within 6 months. RESULTS: A total of 64% of patients experienced modifications in therapy for poorly controlled systolic blood pressure, 71% for poorly controlled diastolic blood pressure, 56% for poorly controlled low-density lipoprotein cholesterol level, and 66% for poorly controlled hemoglobin A1c level. Most frequent modifications were increases in number of drug classes (from 70% to 84%) and increased dosage (from 15% to 40%). An additional 7% to 11% of those with poorly controlled blood pressure, but only 3% to 4% of those with elevated low-density lipoprotein cholesterol level or hemoglobin A1c level, returned to control without therapy modification. Patients with more than 1 of the 3 conditions, higher baseline values, and target organ damage were more likely to receive "appropriate care." LIMITATIONS: Patient preferences and suboptimal adherence to therapy were not measured and may explain some failures to act. CONCLUSIONS: As an additional measure of the quality of care, measuring therapy modifications in response to poor control in a large population is feasible. Many patients with poorly controlled hypertension, dyslipidemia, or diabetes had their therapy modified and, thus, seemed to receive clinically "appropriate care" with this new quality measure.

Comparative resilience of clinical perimetric tests to induced levels of intraocular straylight.

PURPOSE: To investigate the effect of intraocular straylight (IOS) induced by white opacity filters (WOF) on threshold measurements for stimuli employed in three perimeters: standard automated perimetry (SAP), pulsar perimetry (PP) and the Moorfields motion displacement test (MDT).¦METHODS: Four healthy young (24-28 years old) observers were tested six times with each perimeter, each time with one of five different WOFs and once without, inducing various levels of IOS (from 10% to 200%). An increase in IOS was measured with a straylight meter. The change in sensitivity from baseline was normalized, allowing comparison of standardized (z) scores (change divided by the SD of normative values) for each instrument.¦RESULTS: SAP and PP thresholds were significantly affected (P < 0.001) by moderate to large increases in IOS (50%-200%). The drop in motion displacement (MD) from baseline with WOF 5, was approximately 5 dB, in both SAP and PP which represents a clinically significant loss; in contrast the change in MD with MDT was on average 1 minute of arc, which is not likely to indicate a clinically significant loss.¦CONCLUSIONS: The Moorfields MDT is more robust to the effects of additional straylight in comparison with SAP or PP.