Aktualisierte Kurzfassung der Leitlinien zur Pr?vention, Diagnostik und Therapie der nosokomial erworbenen Pneumonie

Hintergrund:  

Die nosokomiale Pneumonie gehört zu den häufigsten nosokomialen Infektionen und ist die häufigste auf der Intensivstation. Die nosokomiale Pneumonie ist mit einer signifikanten Mortalität und Morbidität assoziiert, und ihr Auftreten verschlechtert die Prognose des Patienten deutlich. Nach der Definition der DRGs auch im deutschen Krankenhaussystem ist die nosokomiale Pneumonie überwiegend Sache des Krankenhauses und kann somit nicht nur das Ergebnis der Patientenbehandlung, sondern auch das finanzielle Ergebnis des Krankenhauses beeinträchtigen.     

The REPAIR-AMI and ASTAMI trials: cell isolation procedures: reply

It obviously escaped the notion of Egeland and Brinchman thatthe protocols additionally differ with regard to the washingsteps and buffer components used in the     

Plasma Norharman (β-Carboline) Levels are Elevated in Chronic Alcoholics

Based on the hypothesis that condensation products of neurotransmitters with aldehydes are involved in the pathogenesis of alcoholism, aromatic beta-carbolines (norharman and harman) were measured in the blood plasma of alcoholics and nonalcoholics. The identity of the extracted compounds was confirmed by various elution conditions of the high performance liquid chromatography (HPLC), newly developed radioreceptor assays, and the mass spectrum of norharman. The levels of norharman and harman in nonalcoholics were unchanged after a load with ethanol (1 g/kg body weight). The norharman levels of the alcoholics were significantly higher than that of the nonalcoholic controls (99.5 +/- 26.6 pg/ml vs. 26.9 +/- 10.7 pg/ml; p less than 0.001) and did not change significantly during a 3-week detoxication period. In the subgroup of alcoholics with delirium or hallucinosis, a slight increase of norharman during detoxication could be detected while in alcoholics with vegetative withdrawal symptoms norharman levels dropped slightly over time (p = 0.07). No difference was found with respect to harman between nonalcoholics and alcoholics. These results suggest disturbed regulatory processes in the formation and/or metabolism of norharman in alcoholics. Further investigations are needed to reveal a possible marker function of norharman in alcoholic patients.     

Barusiban suppresses oxytocin-induced preterm labour in non-human primates

Background

Preterm labour (PTL) is a major cause of neonatal mortality and morbidity, and oxytocin (OT) antagonists are potential tocolytics. Atosiban (TRACTOCILE) is a mixed vasopressin V_1A/OT antagonist registered for acute treatment of PTL in Europe. Other off-label drugs have serious side effects. Barusiban is a selective OT antagonist which has reached clinical development. A monkey model with OT-induced PTL was developed to compare barusiban and atosiban. In addition, the feasibility for long-term treatment of PTL with barusiban was explored.

Methods

Conscious pregnant cynomolgus monkeys were monitored for intrauterine pressure (IUP). A sensor for IUP was implanted into the amniotic cavity, and biopotential sensors for electromyogram were attached to the uterus. For short-term experiments, individual low-dose OT infusions induced stable submaximal uterine contractions. Barusiban and atosiban were administered either as intravenous bolus or infusion at high or low doses. For long-term treatment, low-dose OT was infused daily for 3–6 hours to mimic PTL. In addition, continuous high-dose infusions of barusiban (150 μg kg^-1 h^-1) or fenoterol (3 μg kg^-1 h^-1) were administered.

Results

Contractions of 15–40 mmHg were induced with individual OT infusions at 5–90 mU kg^-1 h^-1, and no OT-related desensitization occurred. Correlation was demonstrated between electromyograms and IUP curves. Barusiban was well tolerated and its potency was 4 times higher than atosiban's. Barusiban and atosiban demonstrated >95% efficacy. However, barusiban's duration of action was >13 hours (atosiban's 1–3 hours) and reversible with high-dose OT in emergency situations. OT control and fenoterol-treated monkeys delivered preterm (ca. day 154) and showed an increase in overall IUP. Barusiban-treated animals delivered normally following end of treatment (ca. day 163).

Conclusion

The presented telemetry model provides an excellent method to evaluate PTL drug candidates. OT induced stable repetitive contractions and no desensitisation. Barusiban and atosiban demonstrated high efficacy and rapid onset of action. Barusiban, a selective OT antagonist has higher potency and prolonged duration of action than atosiban. Barusiban effectively suppressed IUP during daily OT-challenges, delayed labour, and prolonged monkeys' pregnancy till term.

     

The use of telescoping guide catheters for coronary sinus cannulation and sub-selecting tributaries in left ventricular lead placement

Introduction Failure to enter the coronary sinus (CS) with a guiding catheter and entering its tributaries remains challenging in left ventricle (LV) pacing lead implants for cardiac resynchronization therapy (CRT). A dual telescoping catheter system (8F outer/6F inner) is designed to provide the ability to adjust the catheter curve size, shape and/or reach to the patients’ anatomy avoiding the need for catheter change. Methods Five different designs for CS cannulation were randomly tested in 64 patients scheduled for CRT device implant. Results In 33 consecutive patients three adaptable telescoping guiding catheter systems were tested per patient, the adaptable catheters had higher overall cannulation success rates (68, 63 and 62%) compared to the fixed shape catheter (46%) and an greater cannulation success rate when the CS location was not known (70, 53 and 72% vs 33% for the fixed shape). In a second group of 31 CRT patients the two telescoping catheters had similar high levels of success (71–80%), with or without using the inner catheter. Conclusions The telescopic system is adaptable to a wide range of anatomical variations in patients and can result in a higher CS cannulation success rate due to its adjustability in the RA in search for the CS ostium. On top of this the inner catheter allows for sub-selecting the CS tributaries.     

Neonatal Exposure to a Combination of N-Methyl-d-aspartate and γ-Aminobutyric Acid Type A Receptor Anesthetic Agents Potentiates Apoptotic Neurodegeneration and Persistent Behavioral Deficits

Background: During the brain growth spurt, the brain develops and modifies rapidly. In rodents this period is neonatal, spanning the first weeks of life, whereas in humans it begins during the third trimester and continues 2 yr. This study examined whether different anesthetic agents, alone and in combination, administered to neonate mice, can trigger apoptosis and whether behavioral deficits occur later in adulthood.

Methods: Ten-day-old mice were injected subcutaneously with ketamine (25 mg/kg), thiopental (5 mg/kg or 25 mg/kg), propofol (10 mg/kg or 60 mg/kg), a combination of ketamine (25 mg/kg) and thiopental (5 mg/kg), a combination of ketamine (25 mg/kg) and propofol (10 mg/kg), or control (saline). Fluoro-Jade staining revealed neurodegeneration 24 h after treatment. The behavioral tests-spontaneous behavior, radial arm maze, and elevated plus maze (before and after anxiolytic)-were conducted on mice aged 55-70 days.

Results: Coadministration of ketamine plus propofol or ketamine plus thiopental or a high dose of propofol alone significantly triggered apoptosis. Mice exposed to a combination of anesthetic agents or ketamine alone displayed disrupted spontaneous activity and learning. The anxiolytic action of diazepam was less effective when given to adult mice that were neonatally exposed to propofol.     

Synthetic Colloids Attenuate Leukocyte-Endothelial Interactions by Inhibition of Integrin Function

Background: It has been suspected that synthetic colloids may interfere with leukocyte adhesion by down-regulation of endothelial cell adhesion molecules. Although inhibition of endothelial inflammation might reduce leukocyte-related tissue injury, the same mechanism may be detrimental for host defense during severe infection. Regarding the widespread use of colloids, the authors performed a laboratory investigation to determine the mechanisms by which synthetic colloids interfere with leukocyte-endothelial interactions.

Methods: Adhesion molecule expression on native and cytokine-activated endothelium from umbilical veins was measured after pretreatment with gelatin and various preparations of dextran or hydroxyethyl starch. Inhibition of neutrophil adhesion to activated endothelium was examined in a flow chamber by perfusion of untreated and colloid-treated neutrophils over colloid-pretreated endothelium at 2 dyn/cm2. Comparisons were made between untreated controls, colloid-pretreated endothelium, and colloid-cotreated neutrophils.

Results: Intercellular adhesion molecule 1, vascular cell adhesion molecule 1, E-selectin, and P-selectin were not attenuated by any colloid. Accordingly, colloid pretreatment of endothelium alone did not reduce neutrophil adhesion. In contrast, when neutrophils were cotreated by addition of colloids to the perfusate immediately before perfusion, adhesion decreased by 31-51% (P < 0.05) regardless of the colloid type. As indicated by the twofold increased rolling fractions, this reduction was due to an inhibition of neutrophil integrins.