Comparison of prone positioning and continuous rotation of patients with adult respiratory distress syndrome: results of a pilot study

OBJECTIVE: To compare prone positioning and continuous rotational therapy with respect to oxygenation and hemodynamics in patients suffering from adult respiratory distress syndrome (ARDS). DESIGN: Randomized, prospective pilot study. SETTING: Intensive care unit at a university hospital. PATIENTS: Twenty-six mechanically ventilated patients with ARDS from nontraumatic causes. INTERVENTIONS: Twelve patients were turned prone (group 1), 14 patients underwent continuous axial rotation from one lateral position to the other with a maximum angle of 124 degrees in specially designed beds (group 2). All patients had received inhaled nitric oxide (NO) therapy before positioning. MEASUREMENTS AND MAIN RESULTS: Gas exchange and hemodynamics were assessed using a pulmonary artery catheter. In both groups, an improvement in PaO2/RFIO2-ratio and intrapulmonary shunt fraction occurred after initiation of NO as well as during the first 72 hrs of positioning therapy. During the study period, seven patients died in group 1 and nine patients in group 2 (p = NS). Comparing the areas under the curve during the first 72 hrs, no significant differences with respect to PaO2/FIO2-ratio, PaCO2, positive end-expiratory and peak inspiratory pressure levels, intrapulmonary shunt fraction, the alveolar-arterial oxygen difference, and oxygen delivery and consumption, as well as cardiac index, pulmonary and arterial blood pressures, and pulmonary arterial occlusion pressure could be detected between the groups. Prone positioning was tolerated well, continuous rotational therapy had to be modified according to hemodynamic instability in three patients. CONCLUSIONS: In severe lung injury, continuous rotational therapy seems to exert effects comparable to prone positioning and could serve as alternative when prone positioning seems inadvisable.     

Evaluation of Seldinger technique emergency cricothyroidotomy versus standard surgical cricothyroidotomy in 200 cadavers

BACKGROUND: Percutaneous cricothyroidotomy is a lifesaving procedure for airway obstruction in trauma victims who need airway establishment and cannot be intubated or in whom intubation has failed. METHODS: The purpose of this study was to examine whether there is a training effect using Seldinger technique emergency cricothyroidotomy (group 1; Arndt Emergency Cricothyroidotomy Catheter Set; Cook Critical Care, Bloomington, IN) versus standard surgical cricothyroidotomy (group 2). Twenty emergency physicians performed five cricothyroidotomies with each method in a total of 200 human cadavers, comparing efficacy and safety (speed, success rate, and injuries). RESULTS: Seven attempts in group 1 and six in group 2 had to be aborted. Time intervals from the start of the procedure to location of the cricothyroid membrane were not significantly different between the groups. However, time to tracheal puncture (P < 0.01) and time to first ventilation (P < 0.001) were significantly longer in group 2. No time effect could be observed in both groups. The airway was accurately placed into the trachea through the cricothyroid membrane in 88.2% (82 of 93) of the cadavers in group 1 and in 84.0% (79 of 94) in group 2 (not significant). No injuries were observed in group 1, whereas there were six punctures of the thyroid vessels in group 2 (P < 0.05). CONCLUSIONS: With respect to time needed for the procedure, the participants performed Seldinger technique emergency cricothyroidotomy significantly faster as compared with standard surgical cricothyroidotomy. Even if no training effect had been observed, the authors believe that it is important to train residents in different methods of cricothyroidotomy in cadavers in addition to training in mannequins to achieve a higher level of efficacy in real-life situations. The shorter time to first ventilation and the fact that no injuries could be observed favor the Seldinger technique.     

Treating acute rhinosinusitis: comparing efficacy and safety of mometasone furoate nasal spray, amoxicillin, and placebo

BACKGROUND: Intranasal corticosteroids used with antibiotics are known to improve rhinosinusitis symptoms compared with antibiotic therapy alone. However, the efficacy of intranasal corticosteroid monotherapy for acute, uncomplicated rhinosinusitis is not established. OBJECTIVES: To evaluate efficacy and safety of mometasone furoate nasal spray (MFNS) versus amoxicillin and placebo in patients with acute, uncomplicated rhinosinusitis. METHODS: In this double-blind, double-dummy trial, subjects (> or =12 years; N = 981) were randomized to MFNS 200 microg once daily or twice daily for 15 days, amoxicillin 500 mg 3 times daily for 10 days, or respective placebo. Follow-up was 14 days. The primary efficacy endpoint was mean am/pm major symptom score over the treatment phase. Secondary efficacy endpoints included total symptom score. Safety assessments included disease recurrence during follow-up and adverse event monitoring. RESULTS: Mometasone furoate nasal spray 200 microg twice daily was significantly superior to placebo (P < .001) and amoxicillin (P = .002) at improving major symptom score. Starting on day 2, MFNS 200 microg twice daily improved total symptom score throughout treatment versus amoxicillin (P = .012) and placebo (P < .001). Global response to treatment was significantly greater with MFNS 200 microg twice daily versus amoxicillin (P = .013) and placebo (P = .001). Although significantly superior to placebo, MFNS 200 microg once daily was not superior to amoxicillin for the primary or secondary efficacy endpoints. All treatments were well tolerated with a similar incidence of adverse events. CONCLUSION: In patients with acute, uncomplicated rhinosinusitis, MFNS 200 microg twice daily produced significant symptom improvements versus amoxicillin and placebo, without predisposing the patient to disease recurrence or bacterial infection.     

Influence of Molecular Weight on Physical and Mechanical Properties of Linear Symmetric S‐(S/B)‐S Triblock Copolymers

Symmetric linear S‐(S/B)‐S triblock copolymers with 80 wt.‐% of PS having a block composition of 20‐60‐20 and a S/B ratio of 70:30 in the middle block are studied with varying molecular weights ( ). Increase in the leads to a change in the morphology from disordered to ordered microphase separated structure, as characterised by TEM and SAXS. Two distinct glass transitions for PS‐ and PB‐rich phases are observed from DMA measurements, which are due to phase separation at high . Rheological studies (master curves) reveal an extended rubbery plateau and a delay in the terminal response with an increase in , whereas a terminal flow behaviour is observed for materials having a disordered nature at low . A brittle‐to‐tough transition is observed from tensile tests with the increase in .

     

Effects of treatment with mometasone furoate dry powder inhaler in children with persistent asthma.

BACKGROUND: Mometasone furoate dry powder inhaler (DPI) has been shown to effectively treat asthma in children. OBJECTIVE: To evaluate the efficacy and safety of 2 dosing regimens of mometasone furoate DPI in the treatment of mild-to-moderate persistent asthma in children previously using inhaled corticosteroids (ICSs). METHODS: A 12-week, multicenter, double-blind, parallel-group, placebo-controlled study evaluated 2 dosing regimens of mometasone furoate DPI (100 microg every evening and 100 microg twice daily) in 296 children 4 to 11 years old with asthma previously using ICSs. The primary efficacy variable was the change in percentage of predicted forced expiratory volume in 1 second (FEV1) from baseline to end point. Secondary efficacy variables included absolute FEV1, forced expiratory flow between 25% and 75% forced vital capacity, morning and evening peak expiratory flow, asthma symptom scores, albuterol use, nocturnal awakenings, response to therapy, and health-related quality of life. RESULTS: Mean changes from baseline at end point in predicted FEV1 were 4.73 and 5.52 percentage points for mometasone furoate DPI, 100 microg every evening and 100 microg twice daily, respectively, the difference of which was not significant, and -1.77 percentage points for placebo (P < or = .002). Significant improvements in secondary efficacy variables were also observed for both mometasone furoate DPI treatments over placebo. Both mometasone furoate DPI doses were well tolerated, and no significant differences were noted among the 3 treatment groups in adverse event reporting. CONCLUSIONS: Both mometasone furoate DPI doses were well tolerated and significantly improved lung function, maintained effective asthma control, and improved quality of life in children with asthma.     

Human kappa light chain targeted Pseudomonas exotoxin A--identifying human antibodies and Fab fragments with favorable characteristics for antibody-drug conjugate development

Antibody-drug conjugates (ADC) represent promising agents for targeted cancer therapy. To allow rational selection of human antibodies with favorable characteristics for ADC development a screening tool was designed obviating the need of preparing individual covalently linked conjugates. Therefore, α-kappa-ETA' was designed as a fusion protein consisting of a human kappa light chain binding antibody fragment and a truncated version of Pseudomonas exotoxin A. α-kappa-ETA' specifically bound to human kappa light chains of human or human-mouse chimeric antibodies and Fab fragments. Antibody-redirected α-kappa-ETA' specifically inhibited proliferation of antigen-expressing cell lines at low toxin and antibody concentrations. Selected antibodies that efficiently delivered α-kappa-ETA' in the novel assay system were used to generate scFv-based covalently linked immunotoxins. These molecules efficiently triggered apoptosis of target cells, indicating that antibodies identified in our assay system can be converted to functional immunoconjugates. Finally, a panel of human epidermal growth factor receptor (EGFR) antibodies was screened--demonstrating favorable characteristics with antibody 2F8. These data suggest that antibodies with potential for Pseudomonas exotoxin A-based ADC development can be identified using the novel α-kappa-ETA' conjugate.     

Evaluation of cardiac scoring models for an Austrian cardiac register

The Austrian Health 2006 Structural Plan of 28 June 2006 requires that reference centres for heart surgery 'participate in result-quality registers (e.g. cardiac registers)'. The aim of the present study was to identify a suitable scoring model for the Austrian register during the run-up to its creation. During the period from November 2004 to December 2005 a survey was done of the actual situation, the organisational and economic possibilities, and the requirements of all Austrian heart centres. General and also specific Austrian basic conditions were defined. Scoring models were then classified and evaluated. The characteristics 'national and international comparability', the associated 'distribution of the scoring system' and 'detailed scientific discussion of the applicability' were found as the main criteria for selection. Economic aspects such as survey and analysis costs, and the everyday practicability of gathering data in the actual situation revealed by the survey, were also included in the evaluation framework. It could be demonstrated that under the given circumstances, the EuroSCORE represented the suitable predictive model.     

Covalent modification of lipids and proteins in rat hepatocytes and in vitro by thioacetamide metabolites

Thioacetamide (TA) is a well-known hepatotoxin in rats. Acute doses cause centrilobular necrosis and hyperbilirubinemia while chronic administration leads to biliary hyperplasia and cholangiocarcinoma. Its acute toxicity requires its oxidation to a stable S-oxide (TASO) that is oxidized further to a highly reactive S,S-dioxide (TASO(2)). To explore possible parallels among the metabolism, covalent binding, and toxicity of TA and thiobenzamide (TB), we exposed freshly isolated rat hepatocytes to [(14)C]-TASO or [(13)C(2)D(3)]-TASO. TLC analysis of the cellular lipids showed a single major spot of radioactivity that mass spectral analysis showed to consist of N-acetimidoyl PE lipids having the same side chain composition as the PE fraction from untreated cells; no carbons or hydrogens from TASO were incorporated into the fatty acyl chains. Many cellular proteins contained N-acetyl- or N-acetimidoyl lysine residues in a 3:1 ratio (details to be reported separately). We also oxidized TASO with hydrogen peroxide in the presence of dipalmitoyl phosphatidylenthanolamine (DPPE) or lysozyme. Lysozyme was covalently modified at five of its six lysine side chains; only acetamide-type adducts were formed. DPPE in liposomes also gave only amide-type adducts, even when the reaction was carried out in tetrahydrofuran with only 10% water added. The exclusive formation of N-acetimidoyl PE in hepatocytes means that the concentration or activity of water must be extremely low in the region where TASO(2) is formed, whereas at least some of the TASO(2) can hydrolyze to acetylsulfinic acid before it reacts with cellular proteins. The requirement for two sequential oxidations to produce a reactive metabolite is unusual, but it is even more unusual that a reactive metabolite would react with water to form a new compound that retains a high degree of chemical reactivity toward biological nucleophiles. The possible contribution of lipid modification to the hepatotoxicity of TA/TASO remains to be determined.