An outbreak of multi-drug-resistant Acinetobacter baumannii on a burns ICU and its control with multi-faceted containment measures.

BACKGROUND: Patients in burns centres are at high risk of acquiring multi-drug-resistant organisms (MDROs) due to the reduced skin barrier and long hospital stay. METHODS: This study reports the investigation and control of an outbreak of MDR Acinetobacter baumannii in a burns centre. The 27 patients hospitalized in the centre during the outbreak were screened regularly, and a total of 132 environmental samples were analysed to identify a potential source. Fourier-transform infra-red (FT-IR) spectroscopy and multi-locus sequence typing were applied to characterize the outbreak strain. RESULTS: Between August and November 2022, the outbreak affected eight patients, with 11 infections and three potentially related fatal outcomes. An interdisciplinary and multi-professional outbreak team implemented a bundle strategy with repetitive admission stops, isolation precaution measures, patient screenings, enhanced cleaning and disinfection, and staff education. FT-IR spectroscopy suggested that the outbreak started from a patient who had been repatriated 1 month previously from a country with high prevalence of MDR A. baumannii. Environmental sampling did not identify a common source. Acquisition of the outbreak strain was associated with a higher percentage of body surface area with burn lesions ≥2a [per percent increase: odds ratio (OR) 1.05, 95% confidence interval (CI) 0.99-1.12; P=0.09], and inversely associated with a higher nurse-to-patient ratio (per 0.1 increase: OR 0.34, 95% CI 0.10-1.12; P=0.06). CONCLUSIONS: Burn patients with a higher percentage of body surface area with burn lesions ≥2a are at high risk of colonization and infection due to MDROs, particularly during periods of high workload. A multi-faceted containment strategy can successfully control outbreaks due to MDR A. baumannii in a burns centre.

A new medication-based prediction score for postoperative delirium in surgical patients: Development and proof of feasibility in a retrospective patient cohort.

Structured risk screening for postoperative delirium (POD) considering prehospital medication is not established. We aimed to develop a POD-risk prediction score based on known risk factors and delirium-risk increasing drugs to be used by pharmacists during medication reconciliation at hospital admission, and to test for feasibility in a retrospective cohort of surgical patients. Therefore, established POD-risk factors and drugs were extracted from the literature and a score was generated. Following this, the score was tested for feasibility in a retrospective 3-month-cohort of surgical patients. For patients with higher scores suggesting higher probability of POD, patient charts were screened for documentation of POD. For development of the score, the following POD-risk factors were defined and points assigned for score calculation: age (≥65 years=1 point/≥75 years=2), male sex (1), renal insufficiency (RI; 1), hepatic impairment (HI; Model-of-endstage-liver-disease (MELD) 10-14=1/≥15=2), delirium-risk increasing drugs (1 point per drug class), anticholinergic drug burden (ACB; ≥3=1). In the retrospective test cohort of 1174 surgical patients these factors concerned: age ≥65 years 567 patients (48%)/≥75 years 303 (26%), male 652 (55%), RI 238 (20%), MELD 10-14 106 (9%)/≥15 65 (5%), ≥ 1 delirium-risk increasing drug 418 (36%), ACB ≥3 106 (9%). The median POD-risk prediction score was 2 (range 0-9). Of 146 patients (12%) with a score ≥ 5, POD was documented for 43 (30%), no evidence for POD for 91 (62%) and data inconclusive for 12 (8%). For scores of ≥ 7, POD was documented for 50% of the patients with sufficient POD documentation. Overall, POD documentation was poor. To summarize, we developed and successfully tested the feasibility of a POD-prediction-score assessable by pharmacists at medication reconciliation at hospital admission.

'Double Whamm' and 'Triple Whamm' combinations in hospitalized surgical patients - real life data from a tertiary teaching hospital.

The 'Triple-Whamm'-combination (TW) of renin-angiotensin-aldosteron-system-inhibitors (RAASI), diuretics and non-steroidal anti-inflammatory drugs (NSAID) can cause acute kidney injury (AKI), especially with additional risk factors like chronic kidney disease (CKD) or surgery. Thus, patients on 'Double-Whammy'-combination (DW) of RAASI and diuretics should receive postoperative NSAID only following risk-benefit-evaluation. Currently, there are no data how often surgical patients take DW/TW at admission and postoperatively. The objective of this study was to firstly assess the prevalence of DW/TW-patients, secondly, to evaluate postoperative NSAID use in DW-patients and possible effects on renal function (RF). In a seven-month retrospective study, the pre-hospital medication of patients admitted to surgical wards of a tertiary teaching hospital was screened for intake of TW-drugs and renal impairment (RI; eGFR <60 ml/min/1.73 m 2 ), respectively. For patients admitted with a DW-combination of RAASI and diuretic and undergoing surgery, postoperative NSAID use was recorded and checked against internal guidelines for postoperative pain management recommending as first line NSAID therapy ibuprofen in bone surgery and novaminsulfone in visceral surgery. If NSAID were taken, RF was followed for five days. Of 2007 patients, 343 (17.1%) presented with DW in pre-hospital medication and 28 (1.4%) with TW, which 19/28 (67.9%) took only on demand. Upon admission, RI was present in 113 (32.9%) DW-patients and 9 (33.3%) TW-patients. 227/343 (66.2%) DW-patients underwent surgery and 34/227 (15.0%) were prescribed postoperative NSAID. 24/227 (10.6%) actually received NSAID and 4/24 (16.7%) had a decrease of RF with one showing AKI. In our hospitalized surgical patients, TW-combination in pre-hospital medication was rare. The intake of DW-combination was common but only a small number actually received NSAID after surgery. When a TW-combination was given postoperatively, renal function decreased in every sixth patient. Thus, the absolute number of AKI following a TW-combination was small, however, the individual risk for TW-caused AKI should be considered when choosing postoperative pain management. Guidelines for postoperative NSAID use should consider the patient individual risk factors for AKI, thereby increasing drug safety.

[CF Lung Disease - a German S3 Guideline: Module 2: Diagnostics and Treatment in Chronic Infection with Pseudomonas aeruginosa]. / S3-Leitlinie: Lungenerkrankung bei Mukoviszidose ­ Modul 2: Diagnostik und Therapie bei der chronischen Infektion mit Pseudomonas aeruginosa.

Cystic Fibrosis (CF) is the most common autosomal-recessive genetic disease affecting approximately 8000 people in Germany. The disease is caused by mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene leading to dysfunction of CFTR, a transmembrane chloride channel. This defect causes insufficient hydration of the epithelial lining fluid which leads to chronic inflammation of the airways. Recurrent infections of the airways as well as pulmonary exacerbations aggravate chronic inflammation, lead to pulmonary fibrosis and tissue destruction up to global respiratory insufficiency, which is responsible for the mortality in over 90 % of patients. The main aim of pulmonary treatment in CF is to reduce pulmonary inflammation and chronic infection. Pseudomonas aeruginosa (Pa) is the most relevant pathogen in the course of CF lung disease. Colonization and chronic infection are leading to additional loss of pulmonary function. There are many possibilities to treat Pa-infection. This is a S3-clinical guideline which implements a definition for chronic Pa-infection and demonstrates evidence-based diagnostic methods and medical treatment for Pa-infection in order to give guidance for individual treatment options.

[Recent antibiotic use in German acute care hospitals - from benchmarking to improved prescribing and quality care]. / Antibiotika-Anwendung 2012/13 in 109 deutschen Akutkrankenhäusern.

BACKGROUND: In view of increasing rates of bacterial resistance and Clostridium difficile infections efforts to enhance appropriate and intelligent antibiotic prescribing have become important. A prerequisite is the availability of reliable antibiotic use data. So far antibiotic consumption data in this country had only a very limited coverage of acute care hospitals. METHODS: We obtained drug dispensing data from 109 German acute care hospital pharmacies and calculated yearly antibiotic use density values stratified for hospital size and type of service / department. Antibiotic use density was expressed as daily doses per 100 patient days (occupied bed days). For daily dose definition, both hospital adapted doses of antibiotics ("recommended daily dose", RDD) as well as the official WHO-defined daily doses (DDD) were used. RESULTS: The overall antibiotic use density was 43.5 RDD/100 patient days (median) with an interquartile range of 36-48 RDD/100 - corresponding to a median of 64.4 DDD/100 (interquartile range, 53-73 DDD/100). The antibiotic use levels in university hospitals were higher than in non-university hospitals that, in turn, showed similar antibiotic use density values across different hospital size categories. Antibiotic use density values for intensive care units were approximately twice as high as for normal wards but the proportion of antibiotic doses prescribed in intensive care per hospital-wide consumption was only 12 % (non-university hospitals) to 18 % (university hospitals). Extensive antibiotic use was also observed in university hospital hematology-oncology departments. Overall, cephalosporins were used slightly more frequently than penicillins, and fluoroquinolones were the third most frequently prescribed drug class. The proportion of first and second generation cephalosporins, and of third and fourth generation cephalosporins ranged between 5-37 % and between < 1 to 29 % of all dispensed antibiotic doses across the hospitals, respectively. The top five used drugs were cefuroxime, piperacillin-tazobactam, ceftriaxon, metronidazole und ciprofloxacin. CONCLUSIONS: Prescribing of antibiotics on almost every second day of hospitalization was extensive and highly variable, and the frequent use of cephalosporins is noteworthy. It is possible that the development of resistance and the rate of Clostridium difficile infection is associated with the diverse antibiotic use intensity and preferences for prescribing of cephalosporins and fluoroquinolones. Continuous antibiotic use surveillance and evaluation of prescribing patterns in acute care with feedback and benchmarking will help optimizing antibiotic use and better assessing strategies to minimize resistance and Clostridium difficile infection, and eventually improve patient safety.

Hemoglobin mass and intravascular volume kinetics during and after exposure to 3,454-m altitude.

High altitude (HA) exposure facilitates a rapid contraction of plasma volume (PV) and a slower occurring expansion of hemoglobin mass (Hbmass). The kinetics of the Hbmass expansion has never been examined by multiple repeated measurements, and this was our primary study aim. The second aim was to investigate the mechanisms mediating the PV contraction. Nine healthy, normally trained sea-level (SL) residents (8 males, 1 female) sojourned for 28 days at 3,454 m. Hbmass was measured and PV was estimated by carbon monoxide rebreathing at SL, on every 4th day at HA, and 1 and 2 wk upon return to SL. Four weeks at HA increased Hbmass by 5.26% (range 2.5-11.1%; P < 0.001). The individual Hbmass increases commenced with up to 12 days of delay and reached a maximal rate of 4.04 ± 1.02 g/day after 14.9 ± 5.2 days. The probability for Hbmass to plateau increased steeply after 20-24 days. Upon return to SL Hbmass decayed by -2.46 ± 2.3 g/day, reaching values similar to baseline after 2 wk. PV, aldosterone concentration, and renin activity were reduced at HA (P < 0.001) while the total circulating protein mass remained unaffected. In summary, the Hbmass response to HA exposure followed a sigmoidal pattern with a delayed onset and a plateau after ∼3 wk. The decay rate of Hbmass upon descent to SL did not indicate major changes in the rate of erythrolysis. Moreover, our data support that PV contraction at HA is regulated by the renin-angiotensin-aldosterone axis and not by changes in oncotic pressure.

CFTR biomarkers: time for promotion to surrogate end-point.

In patients with cystic fibrosis, cystic fibrosis transmembrane conductance regulator (CFTR) biomarkers, such as sweat chloride concentration and/or nasal potential difference, are used as end-points of efficacy in phase-III clinical trials with the disease modifying drugs ivacaftor (VX-770), VX809 and ataluren. The aim of this project was to review the literature on reliability, validity and responsiveness of nasal potential difference, sweat chloride and intestinal current measurement in patients with cystic fibrosis. Data on clinimetric properties were collected for each biomarker and reviewed by an international team of experts. Data on reliability, validity and responsiveness were tabulated. In addition, narrative answers to four key questions were discussed and agreed by the team of experts. The data collected demonstrated the reliability, validity and responsiveness of nasal potential difference. Fewer data were found on reliability of sweat chloride concentration; however, validity and responsiveness were demonstrated. Validity was demonstrated for intestinal current measurement, but further information is required on reliability and responsiveness. For all three end-points, normal values were collected and further research requirements were proposed. This body of work adds useful information to support the promotion of CFTR biomarkers to surrogate end-points and to guide further research in the area.

New clinical diagnostic procedures for cystic fibrosis in Europe.

In the majority of cases, there is no difficulty in diagnosing Cystic Fibrosis (CF). However, there may be wide variation in signs and symptoms between individuals which encourage the scientific community to constantly improve the diagnostic tests available and develop better methods to come to a final diagnosis in patients with milder phenotypes. This paper is the result of discussions held at meetings of the European Cystic Fibrosis Society Diagnostic Network supported by EuroCareCF. CFTR bioassays in the nasal epithelium (nasal potential difference measurements) and the rectal mucosa (intestinal current measurements) are discussed in detail including efforts to standardize the techniques across Europe. New approaches to evaluate the sweat gland, future of genetic testing and methods on the horizon like CFTR expression in human leucocytes and erythrocytes are discussed briefly.

Incidence and predictors of indwelling arterial catheter-related thrombosis in children.

BACKGROUND: Indwelling arterial catheters (IACs) are used for monitoring and blood sampling purposes in intensive care units. Very limited information is available on the incidence and risk factors of IAC-related thrombosis in children. OBJECTIVE: To investigate the incidence and predictors of IAC-related thrombosis in a tertiary care pediatric hospital. METHODS: For a period of 12 months, detailed information was prospectively recorded for all consecutive children requiring IACs. RESULTS: Six hundred and fifteen IACs were placed in a total of 473 children at a median age of 0.56 years for a total of 47440.84 catheter hours. Of the 615 IACs, 418 (68%) were placed in the radial artery, 137 (22%) in the femoral artery, 26 (4%) in the umbilical artery, 11 (2%) in the brachial artery, and 23 (3.7%) in another artery. Thrombosis occurred in 20 cases, reflecting an overall incidence of 3.25%. Eighteen of the 20 IAC-related thrombi were located in the femoral arteries, reflecting a relative incidence of 13% (18/137). Newborn age, lower body weight, low cardiac output and increased hematocrit were significantly related with an increased risk of femoral artery thrombosis. In logistic regression analysis, younger age (P<0.001, odds ratio 6.51) was independently associated with an increased thrombotic risk. CONCLUSIONS: This study demonstrates that arterial thrombosis occurs with an increased incidence in children requiring IACs in the femoral location. Younger age is independently associated with an increased risk of thrombosis. The radial location is safe, and should be preferred to the femoral location.

[Vaccination against bluetongue: safety and immune response in the field]. / Impfung gegen die Blauzungenkrankheit: Verträglichkeit und Immunantwort in der Praxis.

Bluetongue, caused by the bluetongue virus serotype 8 has rapidly spread through Europe since 2006. The first cases in Switzerland were detected in October 2007. The European Union and Switzerland launched a vaccination campaign in June 2008. This study aims to demonstrate the safety and the immune response of the three vaccines used in Switzerland under practical conditions in the field. The trial was carried out in cattle, sheep and goats. Based on the results of this study recommendations for the 2009 campaign are presented.

Non-surgical oncology - Guidelines on Parenteral Nutrition, Chapter 19.

Reduced nutritional state is associated with unfavourable outcomes and a lower quality of life in patients with malignancies. Patients with active tumour disease frequently have insufficient food intake. The resting energy expenditure in cancer patients can be increased, decreased, or remain unchanged compared to predicted values. Tumours may result in varying degrees of systemic pro-inflammatory processes with secondary effects on all significant metabolic pathways. Therapeutic objectives are to stabilise nutritional state with oral/enteral nutrition and parenteral nutrition (PN) and thus to prevent or reduce progressive weight loss. The maintenance or improvement of quality of life, and the increase in the effectiveness and a reduction in the side-effects of antitumor therapy are further objectives. Indications for PN in tumour patients are essentially identical to those in patients with benign illnesses, with preference given to oral or enteral nutrition when feasible. A combined nutritional concept is preferred if oral or enteral nutrition are possible but not sufficient. There are generally no accepted standards for ideal energy and nutrient intakes in oncological patients, particularly when exclusive artificial nutrition is administered. The use of PN as a general accompaniment to radiotherapy or chemotherapy is not indicated, but PN is indicated in chronic severe radiogenic enteritis or after allogenic transplantation with pronounced mucositis or GvH-related gastrointestinal damage for prolonged periods, with particular attention to increased risk of bleeding and infection. No PN is necessary in the terminal phase.

The fate of children with microdeletion 22q11.2 syndrome and congenital heart defect: clinical course and cardiac outcome.

BACKGROUND: This study aimed to evaluate the cardiac outcome for children with microdeletion 22q11.2 and congenital heart defect (CHD). METHODS: A total of 49 consecutive children with 22q11.2 and CHD were retrospectively identified. The CHD consisted of tetralogy of Fallot and variances (n = 22), interrupted aortic arch (n = 10), ventricular septal defect (n = 8), truncus arteriosus (n = 6), and double aortic arch (n = 1). Extracardiac anomalies were present in 46 of 47 children. RESULTS: The median follow-up time was 8.5 years (range, 3 months to 23.5 years). Cardiac surgical repair was performed for 35 children, whereas 5 had palliative surgery, and 9 never underwent cardiac surgery. The median age at repair was 7.5 months (range, 2 days to 5 years). The mean hospital stay was 35 days (range, 7-204 days), and the intensive care unit stay was 15 days (range, 3-194 days). Significant postoperative complications occurred for 26 children (74%), and surgery for extracardiac malformations was required for 21 patients (43%). The overall mortality rate was 22% (11/49), with 1-year survival for 86% and 5-year survival for 80% of the patients. A total of 27 cardiac reinterventions were performed for 16 patients (46%) including 15 reoperations and 12 interventional catheterizations. Residual cardiac findings were present in 25 patients (71%) at the end of the follow-up period. CONCLUSIONS: Children with microdeletion 22q11.2 and CHD are at high risk for mortality and morbidity, as determined by both the severity of the cardiac lesions and the extracardiac anomalies associated with the microdeletion.

Comparison of tracheal tube cuff diameters with internal transverse diameters of the trachea in children.

BACKGROUND: In this study, we evaluated the ratio of the cuff diameters of the Microcuff paediatric tracheal tube (Microcuff PET, Weinheim, Germany) to fluoroscopically measured internal transverse tracheal diameters in children from birth to adolescence. METHODS: With Institutional Ethics Committee approval and parental consent, we measured the internal transverse tracheal diameters from fluoroscopy images in children undergoing cardiac catheterization requiring general anaesthesia with oro-tracheal intubation. Minimal tracheal sealing pressures were assessed at standardized respirator settings. Internal transverse tracheal diameters were compared with cuff diameters at 20 cmH2O cuff pressure. Linear regression analysis was employed to assess the correlation of tracheal diameters with age, height and weight, and to assess the correlation of the cuff/tracheal diameter ratio with sealing pressures. For all tests, P < 0.05 was considered to be statistically significant. RESULTS: One hundred and forty-five patients were studied (62 girls; 83 boys). Transverse tracheal diameters correlated well with age (r = 0.890; P < 0.0001), height (r = 0.900; P < 0.0001) and weight (r = 0.882; P < 0.0001). Tracheal sealing pressures ranged from 4 to 18 cmH2O. The ratio of the tracheal tube cuff diameter to the internal transverse tracheal diameter ranged from 1.06 in tubes with internal diameters of 6.0 and 4.5 mm to 2.01 in a tube with an internal diameter of 3.5 mm (median, 1.43), and did not correlate with tracheal sealing pressures (r = 0.021, P = 0.7999). CONCLUSIONS: The residual diameters of the Microcuff paediatric tracheal tube cuffs were sufficient to cover the measured internal transverse tracheal diameters of children from birth to adolescence. This allowed the internal tracheal mucosal surface to be draped and the trachea to be sealed at very low cuff pressures.

Advantages and disadvantages of different nasal CPAP systems in newborns.

OBJECTIVE: To compare three different systems of continuous positive airway pressure (CPAP): the naso-pharyngeal tube and two-prong systems in newborns, focusing on duration of CPAP, side effects and cost. DESIGN: Randomized clinical study. PATIENTS: Between July 2000 and September 2001 newborns were randomized to three different CPAP systems. Forty infants in two weight groups (>2500 g and 1250-2500 g; 20 patients in each group) were included. RESULTS: In the group >2500 g the median duration of CPAP was 1.1 days (range 0.25-14.3 days). The median time on a naso-pharyngeal CPAP was 1 day (range 0.25-14.3 days), on Hudson prongs 1.6 days (range 0.5-3.3 days) and on the Infant Flow system 0.7 days (range 0.3-13.6 days; p>0.05 for comparison between groups, Fisher's exact test). With naso-pharyngeal CPAP, 2 patients developed moderate nasal injuries. On Hudson, 2 patients developed moderate and three mild nasal injuries. One patient on the Infant Flow showed mild and one moderate nasal injuries. In the weight group 1250-2500 g the median duration of CPAP was 1.1 days (range 0.1-7.0 days). The median time on the naso-pharyngeal tube was 0.9 days (range 0.1-7 days), on Hudson prongs 1.1 days (range 0.7-6.6 days) and on the Infant Flow system 1.3 days (range 0.25-5.9 days; p>0.05 for comparison between groups, Fisher's exact test). With a naso-pharyngeal tube, one infant developed mild and one moderate nasal injuries. On Hudson prongs, two had moderate nasal injuries. On Infant Flow, one newborn showed a severe nasal injury and two mild injuries. None of the patients developed a pneumothorax. CONCLUSION: The naso-pharyngeal tube is an easy, safe and economical CPAP system usable with every common ventilator. For very low birth weight newborns, a prong system may have advantages.

Measurement of activated clotting time in children--comparison of the Celite i-STAT ACT with the Medtronic ACT II.

BACKGROUND: To evaluate a recently introduced blood-saving method for the measurement of activated clotting time (ACT), the Celite i-STAT ACT, by comparing the values obtained with those from the widely used Medtronic ACT II device. METHODS: In a prospective clinical study, we compared ACT values from the i-STAT device with the Medtronic ACT II device in 60 paediatric, interventional, cardiac catheterization procedures necessitating prophylactic heparinization. Blood samples were pair-analyzed using two i-STAT analyzers and one Medtronic ACT II device with double-tube-cartridges before and after heparinization. Data were compared using Bland-Altman bias analysis, Student's t-test and simple regression analysis. RESULTS: Bias and precision between the Medtronic ACT II and the i-STAT ACT values was -5.4 +/- 26.3. The i-STAT and Medtronic ACT II values were similar before heparinization (P = 0.22), but i-STAT ACT values became significantly longer than Medtronic ACT II values after heparinization (P = 0.021). The increase of ACT after heparinization was greater (median 86.3; range 40-187 s) in the i-STAT analyzer than in the Medtronic ACT II analyzer (median 73.0; range 19-235.5 s). Increase in ACT values was inversely affected by intraoperative haemoglobin concentration in the Medtronic ACT II analyzer (P = 0.001) but not in the i-STAT analyzer. CONCLUSION: Activated clotting times obtained from the Celite i-STAT ACT and the Medtronic ACT II demonstrated poor agreement. The technical principles are quite different and the two methods showed diverse susceptibility to intraoperative haemoglobin concentration. Users have to be aware of technique-specific ACT target ranges and their confounders, which need to be provided by the manufacturers.

[Percutaneous carotid angioplasty with stent implantation and protection device against embolism--a prospective study of 100 consecutive cases]. / Perkutane Karotisangioplastiemit Stentimplantation und Embolieprotektion--Eine prospektive Studie bei 100 konsekutiven Behandlungen.

BACKGROUND AND OBJECTIVE: Percutaneous transluminal angioplasty and stenting of internal carotid artery stenosis has been increasingly practiced as an alternative to carotid embolectomy, particularly since the development of cerebral protection devices. 100 consecutive elective percutaneous carotid stenting procedures were carried out in our centre. We here present the clinical outcome and follow-up of these patients. PATIENTS AND METHODS: 69 men and 22 women, average age 69 +/- 10 years with symptomatic (41 %) or asymptomatic and progressive (59 %) > 80 % stenosis of the internal carotid artery were treated. There was a high rate of co-morbidity and a high vascular risk. 64 % would have been excluded from the NASCET trial because of one, 31 % because of two or more contraindications. In 84 % of the patients symptomatic coronary artery disease was present, in 13 % a significantly reduced left ventricular function (LVEF < 40 %).Pre- and post-procedure all patients were given aspirin and clopidogrel and examined by an independent neurologist. 99 stents were placed with the use of an embolic protection device (28 times with distal balloon occlusion, 72 times with a filter device).The follow-up period averaged 10.4 +/- 8.2.(1 - 29 months). RESULTS: The angiographic success rate was 99 %. During the procedure transient neurological symptoms were experienced by 4 % of patients (2x TIA,2x PRIND) and a minor stroke resulted in two. In 90 % of the interventions debris was collected from the embolic protection device. The maximum diameter of particles was 311+/-431 (30 - 1850) micro m. There was some correlation between patients' symptoms prior to stent implantation and maximum particle size (p < 0,04),but none with any other angiographic or clinical parameters. The combined endpoint (death and any stroke) after 30 days occurred 5 times (5 %). A subacute stent thrombosis occurred once, restenosis in two patients. CONCLUSION: Carotid artery stenting with use of a distal embolic protection device is a feasible new alternative to carotid endarterectomy. Our results indicate high success rate and low complication rates, even in patients with severe co-morbidity. The results compare well with surgical figures. Our favourable results are supported by data emerging from current randomized multicenter trials and a large therapy registry. However, long-term follow-up will still be required.

Intracellular calcium: a prerequisite for aldosterone action.

Transport of salt and water in various tissues is under control of the mineralocorticoid hormone aldosterone. As a liphophilic hormone, aldosterone diffuses through the plasma membrane and, then, binds to cytosolic mineralocorticoid receptors in the target cells. After binding to nuclear pore complexes, the activated receptor is translocated to the nucleus where transcription processes are initiated. After a lag period of about 20 minutes hormone-specific early mRNA transcripts leave the nucleus through nuclear pores. Some of the steps in this cascade can be followed by electrophysiology in Xenopus laevis oocyte nuclei. In addition to the genomic pathway, aldosterone exerts a rapid pre-genomic response that involves an increase in intracellular calcium. In this study, we tested for the potential role of Ca(2+) in the genomic response of the hormone. We measured the electrical resistance across the nuclear envelope in response to aldosterone, in presence and absence of intracellular Ca(2+). Nuclear envelope electrical resistance reflects receptor binding to the nuclear pore complexes ("early" resistance peak, 2 minutes after aldosterone), ongoing transcription ("transient" resistance drop, 5-15 minutes after aldosterone) and mRNA export ("late" resistance peak, 20 minutes after aldosterone). Pre-injection of the Ca(2+) chelator EGTA eliminated all electrical responses evoked by aldosterone. The transient resistance drop and the late resistance peak, induced by the hormone, were prevented by the transcription inhibitor actinomycin D, coinjected with aldosterone, while the early resistance peak remained unaffected. We conclude that (i). the presence of intracellular Ca(2+) is a prerequisite for the genomic action of aldosterone. (ii). Intracellular calcium plays a role early in the signaling cascade, either in agonist-receptor interaction, or receptor transport/docking to the nuclear pore complexes.

Variability in infusion pressure and continuous flow rate delivered from pressurized bag pump flush systems.

Using 10 different infusion bag pressure pumps, indicated manometer pressures were compared with measured infusion pressures proximal to the flow-regulating device in an in vitro experiment. Flow rates delivered through the flow-regulating device were gravimetrically measured at different monitored pressure levels. Significant differences were found between manometer and measured infusion pressures among the tested pressure bagpumps (e.g. 500 ml bag volumepressurized to 300 mmHg manometerpressure: 219.6 +/- 7.8 to 407.2 +/- 2.7 mmHg). The infusion pressures were additionally affected by the vertical level of the infusion bag pump and by the volume of the infusion bag. Flow rates delivered through the flow-regulating device were directly correlated to the measured infusion pressure (r2= 0.9926). Differences inflow rates can have a considerable impact on maintaining catheter patency and avoidance of fluid overload and retrograde flushing into the central arterial circulation in neonates and small children. A simple manoeuvre using the invasive pressure transducer allows monitoring and adjustment of the infusion pressure in the clinical setting.

Aldosterone signaling pathway across the nuclear envelope.

We describe the route by which aldosterone-triggered macromolecules enter and exit the cell nucleus of Xenopus laevis oocyte. Oocytes were microinjected with 50 fmol aldosterone and then enucleated 2-30 min after injection. After isolation, nuclear envelope electrical resistance (NEER) was measured in the intact cell nuclei by using the nuclear hourglass technique. We observed three NEER stages: an early peak 2 min after injection, a sustained depression after 5-15 min, and a final late peak 20 min after injection. Because NEER reflects the passive electrical permeability of nuclear pores, we investigated with atomic force microscopy aldosterone-induced conformational changes of individual nuclear pore complexes (NPCs). At the early peak we observed small ( congruent with 100 kDa) molecules (flags) attached to the NPC surface. At the sustained depression NPCs were found free of flags. At the late peak large ( congruent with 800 kDa) molecules (plugs) were detected inside the central channels. Ribonuclease or actinomycin D treatment prevented the late NEER peak. Coinjection of aldosterone (50 fmol) and its competitive inhibitor spironolactone (500 fmol) eliminated the electrical changes as well as flag and plug formation. We conclude: (i) The genomic response of aldosterone can be electrically measured in intact oocyte nuclei. (ii) Flags represent aldosterone receptors on their way into the cell nucleus whereas plugs represent ribonucleoproteins carrying aldosterone-induced mRNA from the nucleoplasm into the cytoplasm. (iii) Because plugs can be mechanically harvested with the atomic force microscopy stylus, oocytes could serve as a bioassay system for identifying aldosterone-induced early genes.