Effect of l-NAME, an inhibitor of nitric oxide synthesis, on plasma levels of IL-6, IL-8, TNFα and nitrite/nitrate in human septic shock

Objectives: We tested the effects of N^G-nitro-L-arginine methyl ester (l-NAME), an inhibitor of nitric oxide (NO) synthesis, on plasma levels of interleukin (IL) IL-6, IL-8, tumor necrosis factor-alpha (TNFα) and nitrite/nitrate (NO ₂ ^? /NO ₃ ^? ) in patients with severe septic shock. Design: Prospective clinical study. Setting: Surgical intensive care unit at a university hospital. Patients: 11 consecutive patients with severe septic shock. Interventions: Standard hemodynamic measurements were made and blood samples taken at intervals before, during, and after a 12-h infusion of l-NAME 1 mg · kg^?1 ·h^?1 for determination of plasma IL-6, IL-8, TNFα and NO ₂ ^? /NO ₃ ^? concentration. Measurements and results: Patients with sepsis had increased plasma levels of IL-6, IL-8, TNFα, and NO ₂ ^? /NO ₃ ^? (p<0.05). Plasma levels of IL-6, IL-8, and NO ₂ ^? /NO ₃ ^? were negatively correlated with systemic vascular resistance (r=?0.62, r=?0.65, and r=?0.78, respectively, all p<0.05). Continuous infusion of l-NAME increased mean arterial pressure and systemic vascular resistance, with a concomitant reduction in cardiac output (all p<0.01). No significant changes were seen in levels of plasma IL-6, IL-8, and NO ₂ ^? /NO ₃ ^? during the 24-h observation period. Plasma levels of TNFα were significantly reduced during l-NAME infusion compared to baseline (p<0.05). Conclusions: NO plays a role in the cardiovascular derangements of human septic shock. Inhibition of NO synthesis with l-NAME does not promote excessive cytokine release in patients with severe sepsis.     

Renal sympathetic denervation therapy in the real world: results from the Heidelberg registry

Introduction

Renal sympathetic denervation (RDN) is a novel treatment option in patients with treatment-resistant arterial hypertension. A subset of recently published randomized and non-randomized trials indicates that RDN leads to sustained lowering of blood pressure (BP) under controlled study conditions. However, registry data that allow evaluation of safety and efficacy in a real-world setting are largely missing.

Methods

Sixty-three consecutive patients with treatment-resistant hypertension underwent RDN with the radiofrequency-based Symplicity? catheter. As part of our prospective registry, treatment efficacy and safety were monitored after 3, 6, and 12 months.

Results

At 6 months follow-up, office systolic BP significantly improved by 19 + 23 mmHg as compared to baseline, while diastolic BP values reduced by 6 + 13 mmHg (p < 0.05). One year after RDN, office BP levels further improved (26 + 25 mmHg in systolic BP and 9 + 13 mmHg in diastolic BP, respectively), even though 19 patients had reduced the number and/or dosage of antihypertensive agents. The response rate, defined as reduction of office systolic BP of ≥10 mmHg, was 73 % after 6 months. Baseline BP was the only significant predictor of blood pressure response, whereas no correlation was found between the number of ablation points and the individual changes in office blood pressure. Interestingly, patients with challenging renal anatomy profited somewhat less from the procedure than those with “normal” renal anatomy. Procedure related adverse events occurred in three patients (4.7 %) and were limited to vascular access complications.

Conclusions

RDN with the Symplicity? system is safe and effective in patients with treatment-resistant hypertension also in a real-world setting.     

Transcutaneous P<Emphasis Type="SmallCaps">tc</Emphasis>CO<Subscript>2</Subscript> measurement in combination with arterial blood gas analysis provides superior accuracy and reliability in ICU patients

Hyper or hypoventilation may have serious clinical consequences in critically ill patients and should be generally avoided, especially in neurosurgical patients. Therefore, monitoring of carbon dioxide partial pressure by intermittent arterial blood gas analysis (PaCO₂) has become standard in intensive care units (ICUs). However, several additional methods are available to determine PCO₂ including end-tidal (PetCO₂) and transcutaneous (PtcCO₂) measurements. The aim of this study was to compare the accuracy and reliability of different methods to determine PCO₂ in mechanically ventilated patients on ICU. After approval of the local ethics committee PCO₂ was determined in n = 32 ICU consecutive patients requiring mechanical ventilation: (1) arterial PaCO₂ blood gas analysis with Radiometer ABL 625 (ABL; gold standard), (2) arterial PaCO₂ analysis with Immediate Response Mobile Analyzer (IRMA), (3) end-tidal PetCO₂ by a Propaq 106 EL monitor and (4) transcutaneous PtcCO₂ determination by a Tina TCM4. Bland–Altman method was used for statistical analysis; p < 0.05 was considered statistically significant. Statistical analysis revealed good correlation between PaCO₂ by IRMA and ABL (R² = 0.766; p < 0.01) as well as between PtcCO₂ and ABL (R² = 0.619; p < 0.01), whereas correlation between PetCO₂ and ABL was weaker (R² = 0.405; p < 0.01). Bland–Altman analysis revealed a bias and precision of 2.0 ± 3.7 mmHg for the IRMA, 2.2 ± 5.7 mmHg for transcutaneous, and ?5.5 ± 5.6 mmHg for end-tidal measurement. Arterial CO₂ partial pressure by IRMA (PaCO₂) and PtcCO₂ provided greater accuracy compared to the reference measurement (ABL) than the end-tidal CO₂ measurements in critically ill in mechanically ventilated patients patients.     

Non-invasive accurate measurement of arterial PCO2 in a pediatric animal model

The PCO₂ in arterial blood (PaCO₂) is a good parameter for monitoring ventilation and acid–base changes in ventilated patients, but its measurement is invasive and difficult to obtain in small children. Attempts have been made to use the partial pressure of CO₂ in end-tidal gas (PetCO₂), as a noninvasive surrogate for PaCO₂. Studies have revealed that, unfortunately, the differences between PetCO₂ and PaCO₂ are too variable to be clinically useful. We hypothesized that end-inspiratory rebreathing, previously shown to equalize PetCO₂ and PaCO₂ in spontaneously breathing humans, would also be effective with positive pressure ventilation. Eight newborn Yorkshire pigs were mechanically ventilated via a partial rebreathing circuit to implement end-inspiratory rebreathing. Arterial blood was sampled and tested for PaCO₂. A variety of alveolar ventilations resulting in different combinations of end-tidal PCO₂ (30–50 mmHg) and PO₂ (35–500 mmHg) were tested for differences between PetCO₂ and PaCO₂ (Pet-aCO₂). The Pet-aCO₂ of all samples was (mean ± 1.96 SD) 0.4 ± 2.7 mmHg. Our study demonstrates that, in ventilated juvenile animals, end-inspiratory rebreathing maintains Pet-aCO₂ to what would be a clinically useful range. If verified clinically, this approach could open the way for non-invasive monitoring of arterial PCO₂ in critically ill patients.     

Modulatory effect of roxithromycin on human neutrophil function

Neutrophils are thought to play a key role in tissue injury. We investigated the effect of roxithromycin, a 14-membered ring macrolide, on human neutrophil functions. The drug inhibitedN-formyl-methionyl-leucyl-phenylalanine (fMLP)-induced superoxide (O ₂ ^? ) production and Ca²⁺ influx of human neutrophils. The inhibition was overcome by adding an inhibitor of cyclic AMP-dependent protein kinase (PKA), H-89. These results suggest that the drug affects O ₂ ^? production and intracellular Ca²⁺ concentration of neutrophils via the action of PKA. Moreover, roxithromycin ameliorated endothelial cell injury induced by neutrophils, which may be, in part, due to the effect of the drug on neutrophils. Thus, roxithromycin may contribute to the treatment of diseases worsened by the excessive action of neutrophils.     

Oxidant scavenger function of ambroxol in vitro: a comparison withN-acetylcysteine

Highly reactive oxygen metabolites play an important role in inflammatory processes in the lung. Ambroxol (2-amino-3,5-dibromo-N-[trans-4-hydroxycyclohexyl]benzylamine) has been shown to reduce oxidant-mediated cell damage. However, the mechanism of this effect remains unclear. In order to evaluate oxidant scavenger function increasing concentrations of ambroxol (0–10^?3 mol/l) were compared with equimolar concentrations ofN-acetylcysteine (NAC) and glutathione (GSH) in vitro to reduce OH^? (hydroxyl radical), HOCl (hypochlorous acid), O ₂ ^? (superoxide anion) and H₂O₂ (hydrogen peroxide). OH^? was measured spectrophotometrically (deoxyribose assay); O ₂ ^? (xanthine/x-oxidase), H₂O₂ and HOCl (HOCl/OCl^?) were determined by chemiluminescence. Ambroxol, NAC and reduced GSH scavenged OH^? significantly at 10^?3 mol/l, while HOCl was inhibited at concentrations ≥10^?4 mol/l completely (P<0.01). NAC and GSH had no anti-O ₂ ^? function, while ambroxol (10^?4 mol/l) reduced O ₂ ^? by 14.3±6.7%. In contrast, GSH and NAC scavenged H₂O₂ at>10^?6 mol/l (P<0.01), while ambroxol had no anti-H₂O₂ effect. Our data demonstrate direct oxidant-reducing capabilities of ambroxol, which may be directly related to the aromatic moiety of the molecule. However, high concentrations (micromolar concentrations) are needed. Due to differences in direct oxidant scavenger function, a combination of ambroxol and NAC could be beneficial in antioxidant therapy.     

Intramucosal–arterial PCO 2 gap fails to reflect intestinal dysoxia in hypoxic hypoxia

Introduction

An elevation in intramucosal–arterial PCO ₂ gradient (ΔPCO ₂) could be determined either by tissue hypoxia or by reduced blood flow. Our hypothesis was that in hypoxic hypoxia with preserved blood flow, ΔPCO ₂ should not be altered.

Methods

In 17 anesthetized and mechanically ventilated sheep, oxygen delivery was reduced by decreasing flow (ischemic hypoxia, IH) or arterial oxygen saturation (hypoxic hypoxia, HH), or no intervention was made (sham). In the IH group (n = 6), blood flow was lowered by stepwise hemorrhage; in the HH group (n = 6), hydrochloric acid was instilled intratracheally. We measured cardiac output, superior mesenteric blood flow, gases, hemoglobin, and oxygen saturations in arterial blood, mixed venous blood, and mesenteric venous blood, and ileal intramucosal PCO ₂ by tonometry. Systemic and intestinal oxygen transport and consumption were calculated, as was ΔPCO ₂. After basal measurements, measurements were repeated at 30, 60, and 90 minutes.

Results

Both progressive bleeding and hydrochloric acid aspiration provoked critical reductions in systemic and intestinal oxygen delivery and consumption. No changes occurred in the sham group. ΔPCO ₂ increased in the IH group (12 ± 10 [mean ± SD] versus 40 ± 13 mmHg; P < 0.001), but remained unchanged in HH and in the sham group (13 ± 6 versus 10 ± 13 mmHg and 8 ± 5 versus 9 ± 6 mmHg; not significant).

Discussion

In this experimental model of hypoxic hypoxia with preserved blood flow, ΔPCO ₂ was not modified during dependence of oxygen uptake on oxygen transport. These results suggest that ΔPCO ₂ might be determined primarily by blood flow.     

Measurement of CO2 response with the breath-by-breath automatic acquisition of the breathing pattern and occlusion pressure

Objective. Our objective is to present a methodology for the automated acquisition and storage of BP and P_0.1 during a CO₂ rebreathing test.Methods. The system consists of a microcomputer with additional circuits and an automatic electronically controlled valve to occlude the inspiratory airway. Data collection and data processing are separate programs. Airway pressure and flow are digitized at a 100-Hz rate, whilePetCO₂ is determined and P_0.1 is measured on a breath-by-breath basis. Off-line processing calculates the BP variables, generates a correlation matrix (Ve/PetCO₂,Ttot/PetCO₂,Ti/PetCO₂,Te/PetCO₂, [Vt/Ti]/PetCO₂, [Ti/Ttot]/PetCO₂, P_0.1/PetCO₂), and edits graphic data. The accuracy of the volume and pressure measurements was tested by comparing known volumes provided by a syringe (n=100) and a series of pressures controlled by a water manometer (n=41) on the one hand, with volumes and pressures measured by the device. The accuracy of the time intervals and P_0.1 was assessed by comparing in 10 healthy subjects the values measured manually on a graphic recording with those provided by the device (n=170).Results. Volumes: V_measured=0.99×V_controlled,r=0.99,p<0.001. Pressures: P_measured=0.97×P_controlled+0.09,r=0.98,p<0.001. Inspiratory time:Ti _automatic=0.91×Ti _graphic+0.22,r=0.93,p<0.001. Expiratory time:Te _automatic=0.93×Te _graphic+0.34,r=0.95,p<0.001. Occlusion pressure: P_{0.1 automatic}=0.95×P_{0.1 graphic}+0.62,r=0.94,p<0.001. Reproducibility was assumed to be represented by the intraindividual coefficient of variation of the CO₂ response. The comparison of an automatic breath-to-breath method with a graphic manual recording revealed significantly less variability with the former (Ve/PetCO₂: 15.2±4.5% vs 22.5±6.3%,p<0.01; P_0.1/PetCO₂: 8.3±4.3% vs 19.7±7.2%,p<0.001; [Vt/Ti]/PetCO₂: 9.1±3.5% vs 14.5±5.3%,p<0.05).Conclusion. Our automated acquisition and storage of waveforms and breath-by-breath determination of BP and P_0.1 provide an easy and thorough analysis of the respiratory response to CO₂ and decrease the variability of the results.     

In vitro Characterization of Uptake Mechanism of l-[methyl-3H]-methionine in Hepatocellular Carcinoma

Purpose

Methionine (Met) could be a useful imaging biomarker for the diagnosis of hepatocellular carcinoma (HCC), as demonstrated by PET imaging with l-[methyl-¹¹C]-Met. In HCC cells, protein synthesis mainly contributes to radiopharmaceutical uptake. In contrast, lipid synthesis via the phosphatidylethanolamine (PE) methylation pathway is the major metabolic route of l-[methyl-¹¹C]-Met in normal hepatocytes, which contributes to the background contrast observed in PET images. However, the mechanisms of amino acid transport and the roles of the two key enzymes, methionine adenosyltransferase (MAT) and phosphatidylethanolamine N-methyltransferase (PEMT), are not yet completely understood. The aim of this study was to investigate the roles of the amino acid transporters and these two key enzymes in the uptake of l-[methyl-¹¹C]-Met in HCC cells.

Procedures

A well-differentiated woodchuck HCC cell line, WCH17, was used for the study. The amino acid transporter of WCH17 cells was assayed to investigate the Met transport process in HCC. WCH17 cells were treated with 5 mM S-adenosylmethionine (SAM) for 8, 16, 24, and 48 h to downregulate MAT2A gene expression. Control or SAM-treated WCH17 cells were pulsed with l-[methyl-³H]-Met for 5 min and chased with cold media to mimic the rapid blood clearance of radiolabeled Met (pulse-chase experiment). In parallel, WCH17 cells were transfected with a mouse liver PEMT2 expression vector, and the pulse-chase experiment was performed to investigate the uptake of the radiolabeled Met in HCC cells. The water-soluble, protein, and lipid phases from the total uptake were subsequently extracted and measured, respectively.

Results

Met was transported into HCC cells via a facilitative transport process, which was characterized as system L and ASC-like, Na⁺ dependent, and low affinity with partial energy dependence. The total uptake of l-[methyl-³H]-Met was decreased in HCC cells with SAM treatment. This reduction pattern followed that of MAT2A expression (the duration of SAM treatment). The incorporated ³H was mostly distributed in the protein phase and, to a lesser degree, in the lipid phase via PE methylation pathway in HCC cells with SAM treatment. The downregulated MAT2A expression led to the decreased uptake in protein and water-soluble phases. In addition, an increased uptake in the lipid phase was observed in WCH17 cells transfected with PEMT2 expression vector.

Conclusions

The amino acid transport processes may be responsible for the rapid accumulation of radiolabeled Met after the intravenous injection of tracers for the imaging of HCC. Upregulated MAT2A expression and impaired PEMT2 activities in HCC are associated with the specific metabolic pattern of l-[methyl-¹¹C]-Met detected by PET.     

Early intermittent noninvasive ventilation for acute chest syndrome in adults with sickle cell disease: a pilot study

Purpose

Alveolar hypoxia and hypoxic vasoconstriction lead to trapping of sickle cells within the pulmonary vasculature. Improving alveolar ventilation and oxygenation may improve the outcome of acute chest syndrome (ACS).

Methods

Prospective randomized single-center open study from November 1998 to February 2002 to test whether noninvasive ventilation (NIV) was more effective than oxygen alone in improving oxygenation on day 3 in adults with ACS and to evaluate the effects on pain, transfusion requirements, and length of stay.

Results

Seventy-one consecutive ACS episodes in 67 patients were randomly allocated to oxygen (n = 36) or NIV (n = 35) for 3 days in a medical step-down unit. Baseline respiratory rate and pain score were higher in the NIV group. NIV promptly lowered the respiratory rate, raised $ {\text{Pa}}_{{\text{O}_{2}}} $ , and decreased alveolar–arterial oxygen gradient $ (({\text{A}} - {\text{a}})_{{{\text{O}}_{ 2} }} ) $ , which remained unchanged with oxygen alone. $ {\text{Pa}}_{{{\text{CO}}_{ 2} }} $ significantly worsened only in the oxygen group. On day 3, the groups did not differ regarding the proportion of episodes with normal $ {\text{Pa}}_{{{\text{O}}_{ 2} }} $ (35% with NIV and 25% with oxygen; P = 0.5) or $ (({\text{A}} - {\text{a}})_{{{\text{O}}_{ 2} }} ) $ . Patient satisfaction and compliance were lower with NIV. No differences were noted in pain relief, transfusions, or length of stay. In the subgroup of patients with severe hypoxemia $ ( {\text{Pa}}_{{{\text{O}}_{ 2} }} \le 6 5\,{\text{mmHg)}} $ , physiological variables also improved faster with NIV, the differences being slightly more pronounced.

Conclusions

Respiratory rate and gas exchange improved faster with NIV. However, NIV failed to significantly reduce the number of patients remaining hypoxemic at day 3, and was associated with greater patient discomfort.     

Solvent extraction of rare earths elements from nitrate media in DMDOHEMA/ionic liquid systems: performance and mechanism studies

Extraction of La(iii), Eu(iii) and Fe(iii) was compared in n-dodecane and two ionic liquids (ILs) (1-ethyl-1-butylpiperidinium bis (trifluoromethylsulfonyl)imide [EBPip⁺] [NTf₂⁻] and 1-ethyl-1-octylpiperidinium bis (trifluoromethylsulfonyl)imide [EOPip⁺] [NTf₂⁻]). Using the extractant N,N′-dimethyl-N,N′-dioctylhexylethoxymalonamide (DMDOHEMA), the effect of pH was investigated in detail to recover extraction mechanisms. The use of ILs as the organic solvent instead of n-dodecane, greatly enhances extraction efficiency, and an ionic liquid with a shorter alkyl chain [EBPip⁺] [NTf₂⁻] provides higher extraction than [EOPip⁺] [NTf₂⁻]. The mechanistic study points out that for low nitric acid concentrations ([HNO₃] ≤ 0.01 M), metal is extracted via a cation of the ionic liquids, while for higher nitric acid concentrations ([HNO₃] ≥ 1.0 M), extraction occurs through pure solvation mechanism of DMDOHEMA as in conventional diluents. This latter case is of high interest for applications, as higher extraction can be obtained without any loss of ILs by ion exchange mechanisms.

Extraction of La(iii), Eu(iii) and Fe(iii) was compared in n-dodecane and in two ionic liquids (ILs) [EBPip⁺] [NTf₂⁻] and [EOPip⁺] [NTf₂⁻]. Extraction mechanisms have been investigated as a function of pH.     

Three-dimensional prediction of free-flap volume in autologous breast reconstruction by CT angiography imaging

Purpose

   The diagnostic use of computer tomography angiography (CTA) to identify perforating blood vessels for abdominal free-flap breast reconstruction was extended to estimate the three-dimensional (3D) preoperative flap volume and to compare it with the real intraoperative flap weights in order to (1) evaluate the accuracy of CTA-based 3D flap volume prediction, and (2) to analyze abdominal tissue estimation for required breast volume reconstruction.

Methods

   Preoperative CTA was performed in 54 patients undergoing unilateral breast reconstruction with a free, deep, inferior epigastric artery perforator flap. 3D flap volumes ( \(\hbox {cm}^{3}\) ) based on CTA data were calculated and compared with the actual intraoperative flap weight (g). In addition, a breast volume to flap volume ratio was calculated to analyze whether the estimated 3D abdominal flap volume would match that of the breast to be removed.

Results

   40 CTA data sets (74.1 %) fulfilled the technical requirements for a reliable determination of flap volume. 3D CTA flap volume prediction showed no relevant differences to the actual flap weight (p = 0.44) and high correlations (r = 0.998, \(p < 0.001\) ), allowing a prediction accuracy within 0.29 \(\pm \) 3.0 % (range: from \(-\) 8.77 to 5.67 %) of the real flap weight. Significantly larger flap volumes were harvested compared with the actually required breast volumes ( \(p < 0.001\) ), leading to an average of 21 % of the remnant flap tissue potentially being discarded.

Conclusions

   CTA-based 3D flap volume prediction provides accurate preoperative guidelines concerning the needed amount of abdominal tissue that can be harvested to achieve acceptable symmetry.     

In Vivo Magnetic Resonance Imaging of Transgenic Mice Expressing Human Ferritin

Objective

This study aims to produce the transgenic mice (TG) engineered for magnetic resonance imaging (MRI) studies based on the ubiquitous expression of ferritin MRI reporter gene in diverse tissues.

Procedures

Transgenic mice (TG) expressing myc-tagged human heavy chain ferritin (myc-hFTH) under the control of a ubiquitous CAG promoter were produced. The expression of myc-hFTH in diverse tissues of the myc-hFTH TG was assessed by RT-PCR, Western blotting, and immunohistochemistry. The iron accumulation and the deposition of ferritin aggregates in tissues of myc-hFTH TG and WT were analyzed by Prussian blue staining and transmission electron microscopy. The myc-hFTH TG (n?=?9) and wild-type mice (WT) (n?=?4) were subjected to MRI on 9.4 T MR scanner. An eight-point T ₂ ^* mapping was performed using a multiple gradient echo sequence, and T ₂ ^* value was estimated pixel by pixel by using a routine least-squares fitting algorithm.

Results

We generated the myc-hFTH TG expressing myc-hFTH in brain, heart, liver, lung, spleen, pancreas, kidney, and intestine. The myc-hFTH TG showed no apparent pathological symptoms and no histological changes compared to WT. The expression of myc-hFTH in the brain and liver tissues of myc-hFTH TG led to a significant decrease in T₂* values, as shown by noninvasive MRI, compared to WT (P?<?0.05, TG vs. WT).

Conclusions

This study demonstrates that the novel myc-hFTH TG, which expresses an MRI reporter in many tissues, would be a valuable animal model of FTH-based molecular imaging in which to study potential therapies for cell and tissue grafting using an MRI technique. These mice could also serve to study disease related with iron metabolism.     

Prone ventilation reduces mortality in patients with acute respiratory failure and severe hypoxemia: systematic review and meta-analysis

Background

Prone position ventilation for acute hypoxemic respiratory failure (AHRF) improves oxygenation but not survival, except possibly when AHRF is severe.

Objective

To determine effects of prone versus supine ventilation in AHRF and severe hypoxemia [partial pressure of arterial oxygen (PaO₂)/inspired fraction of oxygen (FiO₂) <100 mmHg] compared with moderate hypoxemia (100 mmHg ≤ PaO₂/FiO₂ ≤ 300 mmHg).

Design

Systematic review and meta-analysis.

Data Sources

Electronic databases (to November 2009) and conference proceedings.

Methods

Two authors independently selected and extracted data from parallel-group randomized controlled trials comparing prone with supine ventilation in mechanically ventilated adults or children with AHRF. Trialists provided subgroup data. The primary outcome was hospital mortality in patients with AHRF and PaO₂/FiO₂ <100 mmHg. Meta-analyses used study-level random-effects models.

Results

Ten trials (N = 1,867 patients) met inclusion criteria; most patients had acute lung injury. Methodological quality was relatively high. Prone ventilation reduced mortality in patients with PaO₂/FiO₂ <100 mmHg [risk ratio (RR) 0.84, 95% confidence interval (CI) 0.74–0.96; p = 0.01; seven trials, N = 555] but not in patients with PaO₂/FiO₂ ≥100 mmHg (RR 1.07, 95% CI 0.93–1.22; p = 0.36; seven trials, N = 1,169). Risk ratios differed significantly between subgroups (interaction p = 0.012). Post hoc analysis demonstrated statistically significant improved mortality in the more hypoxemic subgroup and significant differences between subgroups using a range of PaO₂/FiO₂ thresholds up to approximately 140 mmHg. Prone ventilation improved oxygenation by 27–39% over the first 3 days of therapy but increased the risks of pressure ulcers (RR 1.29, 95% CI 1.16–1.44), endotracheal tube obstruction (RR 1.58, 95% CI 1.24–2.01), and chest tube dislodgement (RR 3.14, 95% CI 1.02–9.69). There was no statistical between-trial heterogeneity for most clinical outcomes.

Conclusions

Prone ventilation reduces mortality in patients with severe hypoxemia. Given associated risks, this approach should not be routine in all patients with AHRF, but may be considered for severely hypoxemic patients.     

Usability of unbiased nonlocal means for de-noising intraoperative magnetic resonance images in neurosurgery

Purpose

   Intraoperative magnetic resonance imaging (iMRI) is a powerful tool that allows real-time image-guided excision of brain tumors. However, low magnetic field iMRI devices may produce low-quality images due to nonideal imaging conditions in the operating room and additional noise of unknown origin. The purpose of this study was to evaluate a three-dimensional unbiased nonlocal means filter for iMRI (UNLM-i) that we developed in order to enhance image quality and increase the diagnostic value of iMRI.

Methods

   We first evaluated the effect of UNLM by assessing the modulation transfer function (MTF) and Weiner spectrum (WS) of UNLM in simulated imaging. We then tested the diagnostic value of UNLM-i de-noising by applying it to a series of randomly chosen iMR images that were assessed by 4 neurosurgeons and 4 radiological technologists using a 5-point rating scale to compare 13 parameters, including tumor visibility, edema, and sulci, before and after de-noising.

Results

   Unbiased nonlocal means provided better MTF in comparison with other filters, and the WS for UNLM de-noising was reduced for all spatial frequencies. Postprocessing UNLM-i allowed de-noising with preserved edges and \(>\) twofold improvement in the signal-to-noise ratio without extending the MRI scanning time ( \(p < 0.001\) ). The diagnostic value of UNLM-i de-noising was rated as “superior” or “better” in \(>\) 80 % of cases in terms of contrast between white and gray matter and visibility of sulci, tumor, and edema ( \(p < 0.001\) ).

Conclusions

   Unbiased nonlocal means filter for iMRI de-noising proved very useful for image quality enhancement and assistance in the interpretation of iMR images.     

Placental membrane transport

Brush border (microvillous) plasma membranes (BBM) and the basal surfaces (BCM) from the syncytiotrophoblast of human term placenta were prepared by a method of sonication, dialysis and differential centrifugation in specific buffer systems. Such plasma membranes formed closed, osmotically active, right-side-out vesicles in which amino acid transport could be studied unidirectionally by a carefully designed membrane filtration assay under reduced pressure. In such vesicles,l-leucine (1 mM) was found to be transported in a time-dependent manner, peak accumulation being attained at 45 s in both BBM and BCM. The accumulation of leucine in the vesicles was dependent on an inward NaCl gradient, as replacing the Na⁺with K⁺, Li⁺and choline, or replacing the Cl^? with SO ₄ ^2? failed to influence the amino acid movement. Leucine transport in the vesicles also appeared to be dependent on the substrate concentration, indicating saturation at a higher concentration. The transport process showed a k_t (affinity constant) of 3.85 and 6.67 mM, while the values recorded for the J_max (maximum apparent initial velocity) were 270.27 and 384.62 nmol/mg protein^?1 per min in the BBM and BCM respectively. Leucine transport was inhibited by a number of amino acids, among which amino isobutyric acid (AIB) produced the maximum inhibition. The k_i (inhibition constant) for different amino acids has also been listed. Lysine showed the least k_i value, thus showing it to be the most inhibitory compound. These findings are discussed in relation to the mechanism and regulation of transplacental amino acid transfer.     

A pilot study on magnetic navigation for transcatheter aortic valve implantation using dynamic aortic model and US image guidance

Purpose   In this paper, we propose a pilot study for transcatheter aortic valve implantation guided by an augmented magnetic tracking system (MTS) with a dynamic aortic model and intra-operative ultrasound (US) images. Methods    The dynamic 3D aortic model is constructed from the preoperative 4D computed tomography, which is animated according to the real-time electrocardiograph (ECG) input of patient. Before the procedure, the US probe calibration is performed to map the US image coordinate to the tracked device coordinate. A temporal alignment is performed to synchronize the ECG signals, the intra-operative US image and the tracking information. Thereafter, with the assistance of synchronized ECG signals, the spatial registration is performed by using a feature-based registration. Then the augmented MTS guides the surgeon to confidently position and deploy the transcatheter aortic valve prosthesis to the target. Results   The approach was validated by US probe calibration evaluation and animal study. The US calibration accuracy achieved $1.37\pm 0.43\, \text{ mm}$ , whereas in the animal study on three porcine subjects, fiducial, target, deployment distance and tilting errors reached $3.16\pm 0.55\,\text{ mm}$ , $3.80\pm 1.83\,\text{ mm}$ , $3.13\pm 1.12\,\text{ mm}$ and $5.87\pm 2.35^{\circ }$ , respectively. Conclusion   Our pilot study has revealed that the proposed approach is feasible and accurate for delivery and deployment of transcatheter aortic valve prosthesis.     

Multimodal Imaging for Early Functional Response Assessment of 90Y-/177Lu-DOTATOC Peptide Receptor Targeted Radiotherapy with DW-MRI and 68Ga-DOTATOC-PET/CT

Purpose

The purpose of this study is to investigate the utility of contrast-enhanced magnetic resonance imaging (CE-MRI), diffusion-weighted MRI (DW-MRI), and ⁶⁸Ga-DOTATOC positron emission tomography/computer tomography (⁶⁸Ga-DOTATOC PET/CT) in the assessment of response to loco-regional peptide receptor radiotherapy (PRRT) with ⁹⁰Y-/¹⁷⁷Lu-DOTATOC in patients with hepatic metastases from gastro-entero-pancreatic neuroendocrine tumors (GEP-NET).

Procedures

CE-MRI, DW-MRI, and ⁶⁸Ga-DOTATOC-PET/CT images were acquired before and 3 months after one to two cycles of intra-arterial ⁹⁰Y-/¹⁷⁷Lu-DOTATOC therapy in 14 patients (nine female, five male; mean age, 54?±?9 years; range, 41–69 years) with hepatic metastases from GEP-NET. A total of 38 liver metastases were defined as target lesions for which the longest diameter, mean apparent diffusion coefficient (ADC_mean) and maximum standardized uptake value (SUV_max) were assessed. Based on changes in size on follow-up imaging, target lesions were classified as responding (RL) or nonresponding (NRL). Relative changes in tumor size, ADC_mean, and SUV_max were compared between the two subgroups.

Results

A total of 27 responding and 11 nonresponding lesions were successfully evaluated. Mean ADC_mean increased significantly in RL (p?=?0.011) as well as NRL (p?=?0.025). A significant correlation was found between baseline ADC_mean and both the percent ADC_mean change (p?=?0.033) and decrease in lesion size after therapy (diameter p?=?0.006; volume p?=?0.002). SUV_max of RL declined significantly by 24.1 % (p?=?0.014) and remained nearly unchanged in NRL. The change of SUV_max correlated significantly with the pretreatment SUV_max (p?<?0.001) and the change in lesion diameter (p?=?0.009). NRL with an ADC_mean change >0.31?×?10^?3 mm²/s on first follow-up imaging showed a decrease in size in the long-term course.

Conclusion

These results suggest that both DW-MRI and DOTATOC-PET imaging provide potential biomarkers for early assessment of treatment and stratification of therapy response, but that DW-MRI should be interpreted only in combination with SSTR expression and morphologic changes.     

The dielectric relaxation behavior induced by sodium migration in the Na2CoSiO4 structure within a three-dimensional Co–O–Si framework

The disodium cobalt(ii) orthosilicate material (NCS) has been synthesized using improved solid-state (NCS-SS) and co-precipitation (NCS-CP) methods of synthesis. The Rietveld refinement of the XRD pattern of Na₂CoSiO₄ has demonstrated an orthorhombic crystal system with the space groups Pna2₁ and Pbca for NCS-SS and NCS-CP respectively. The elemental mapping of microstructures by scanning electron microscopy-energy dispersive spectroscopy (SEM-EDS) showed the porous morphology and the homogenous particles of the Na₂CoSiO₄ powders. Their dielectric properties were measured in the frequency and temperature ranges of 0.1–10⁶ Hz and 383–613 K respectively. Different dielectric relaxation phenomena associated with the Na⁺-ion migration through different paths were displayed in relation with the temperature and frequency. The decrease and increase in the dielectric properties were found to be dependent on the formation of short-range ordered structure formed after the migration of Na⁺-ions. In the present work, an attempt has been made to study the relation between the structural properties and the dielectric process. Thus, interesting insights into the transport behavior of Na⁺-ions in different chemical environments were obtained. This in turn provides an effective procedure to probe the relationship between the diffusion pathway of Na⁺-ions and the dielectric response.

A disodium cobalt(ii) orthosilicate material has been synthesized using improved solid-state and co-precipitation methods of synthesis. The Rietveld refinement of the XRD pattern of Na₂CoSiO₄ demonstrated an orthorhombic crystal system.     

Automated differentiation of glioblastomas from intracranial metastases using 3T MR spectroscopic and perfusion data

Purpose   Differentiation of glioblastomas from metastases is clinical important, but may be difficult even for expert observers. To investigate the contribution of machine learning algorithms in the differentiation of glioblastomas multiforme (GB) from metastases, we developed and tested a pattern recognition system based on 3T magnetic resonance (MR) data. Materials and Methods   Single and multi-voxel proton magnetic resonance spectroscopy (1H-MRS) and dynamic susceptibility contrast (DSC) MRI scans were performed on 49 patients with solitary brain tumors (35 glioblastoma multiforme and 14 metastases). Metabolic (NAA/Cr, Cho/Cr, (Lip  $+$  Lac)/Cr) and perfusion (rCBV) parameters were measured in both intratumoral and peritumoral regions. The statistical significance of these parameters was evaluated. For the classification procedure, three datasets were created to find the optimum combination of parameters that provides maximum differentiation. Three machine learning methods were utilized: Naïve-Bayes, Support Vector Machine (SVM) and $k$ -nearest neighbor (KNN). The discrimination ability of each classifier was evaluated with quantitative performance metrics. Results   Glioblastoma and metastases were differentiable only in the peritumoral region of these lesions ( $p<0.05$ ). SVM achieved the highest overall performance (accuracy 98 %) for both the intratumoral and peritumoral areas. Naïve-Bayes and KNN presented greater variations in performance. The proper selection of datasets plays a very significant role as they are closely correlated to the underlying pathophysiology. Conclusion   The application of pattern recognition techniques using 3T MR-based perfusion and metabolic features may provide incremental diagnostic value in the differentiation of common intraaxial brain tumors, such as glioblastoma versus metastasis.