Use of linezolid in neonatal and pediatric inpatient facilities-results of a retrospective multicenter survey

The purpose of this investigation was to describe the use of linezolid in pediatric inpatient facilities. A retrospective multicenter survey including data from nine participating tertiary care pediatric inpatient facilities in Germany and Austria was undertaken. Data on 126 off-label linezolid treatment courses administered to 108 patients were documented. The survey comprises linezolid treatment in a broad spectrum of clinical indications to children of all age groups; the median age was 6.8 years (interquartile range 0.6-15.5 years; range 0.1-21.2 years; ten patients were older than 18 years of age but were treated in pediatric inpatient units). Of the 126 treatment courses, 27 (21%) were administered to preterm infants, 64 (51%) to pediatric oncology patients, and 5% to patients soon after liver transplantation. In 25%, the infection was related to a medical device. Linezolid iv treatment was started after intensive pre-treatment (up to 11 other antibiotics for a median duration of 14 days) and changed to enteral administration in only 4% of all iv courses. In 39 (53%) of 74 courses administered to children older than 1 week and younger than 12 years of age, the dose was not adjusted to age-related pharmacokinetic parameters. In only 17 courses (13%) was a pediatric infectious disease consultant involved in the clinical decision algorithm. Linezolid seemed to have contributed to a favorable outcome in 70% of all treatment courses in this survey. Although retrospective, this survey generates interesting data on the off-label use of linezolid and highlights several important clinical aspects in which the use of this rescue antibiotic in children might be improved.

Using micropower impulse radar technology to screen for pneumothorax: an international bi-institutional study

Pneumothoraces (PTXs) are a common entity in thoracic trauma. Micropower impulse radar (MIR) has been able to detect PTXs in surgical patients. However, this technology has not been tested previously on trauma patients. The purpose of this study was to determine the sensitivity and specificity of MIR to detect clinically significant PTXs. We hypothesized that MIR technology can effectively screen trauma patients for clinically significant PTXs.

Can handheld micropower impulse radar technology be used to detect pneumothorax? Initial experience in a European trauma centre

BACKGROUND: Pneumothoraces are a common injury pattern in emergency medicine. Rapid and safe identification can reduce morbidity and mortality. A new handheld, battery powered device, the Pneumoscan (CE 561036, PneumoSonics Inc., Cleveland, OH, USA), using micropower impulse radar (MIR) technology, has recently been introduced in Europe for the rapid and reliable detection of PTX. However, this technology has not yet been tested in trauma patients. This is the first quality control evaluation to report on emergency room performance of a new device used in the trauma setting. MATERIAL AND METHODS: This study was performed at a Level I trauma centre in Switzerland. All patients with thoracic trauma and undergoing chest X-ray and CT-scan were eligible for the study. Readings were performed before the chest X-ray and CT scan. The patients had eight lung fields tested (four on each side). All readings with the Pneumoscan were performed by two junior residents in our department who had previously received an instructional tutorial of 15min. The qualitative MIR results were blinded, and stored on the device. We then compared the results of the MIR to those of the clinical examination, chest X-ray and CT-scan. RESULTS: 50 patients were included, with a mean age of 46 (SD 17) years. Seven patients presented with PTX diagnosed by CT; six of these were detected by Pneumoscan, leading to an overall sensitivity of 85.7 (95% confidence interval 42.1-99.6)%. Only two of seven PTX were found during clinical examination and on chest X-ray (sensitivity 28.6 (95% CI 3.7-71.0)%). Of the remaining 43 of 50 patients without PTX, one false-positive PTX was found by the Pneumoscan, resulting in a specificity of 97.7 (95% CI 87.7-99.9)%. DISCUSSION: The Pneumoscan is an easy to use handheld technology with reliable results. In this series, the sensitivity to detect a PTX by the Pneumoscan was higher than by clinical examination and chest X-ray. Further studies with higher case numbers and a prospective study design are needed to confirm our findings.

Relative contributions of connexins 40 and 43 to atrial impulse propagation in synthetic strands of neonatal and fetal murine cardiomyocytes

Atrial tissue expresses both connexin 40 (Cx40) and 43 (Cx43) proteins. To assess the relative roles of Cx40 and Cx43 in atrial electrical propagation, we synthesized cultured strands of atrial myocytes derived from mice with genetic deficiency in Cx40 or Cx43 expression and measured propagation velocity (PV) by high-resolution optical mapping of voltage-sensitive dye fluorescence. The amount of Cx40 and/or Cx43 in gap junctions was measured by immunohistochemistry and total or sarcolemmal Cx43 or Cx40 protein by immunoblotting. Progressive genetic reduction in Cx43 expression decreased PV from 34+/-6 cm/sec in Cx43(+/+) to 30+/-8 cm/sec in Cx43(+/-) and 19+/-11 cm/sec in Cx43(-/-) cultures. Concomitantly, the cell area occupied by Cx40 immunosignal in gap junctions decreased from 2.0+/-1.6% in Cx43(+/+) to 1.7+/-0.5% in Cx43(+/-) and 1.0+/-0.2% in Cx43(-/-) strands. In contrast, progressive genetic reduction in Cx40 expression increased PV from 30+/-2 cm/sec in Cx40(+/+) to 40+/-7 cm/sec in Cx40(+/-) and 45+/-10 cm/sec in Cx40(-/-) cultures. Concomitantly, the cell area occupied by Cx43 immunosignal in gap junctions increased from 1.2+/-0.9% in Cx40(+/+) to 2.8+/-1.4% in Cx40(+/-) and 3.1+/-0.6% in Cx40(-/-) cultures. In accordance with the immunostaining results, immunoblots of the Triton X-100-insoluble fraction revealed an increase of Cx43 in gap junctions in extracts from Cx40-ablated atria, whereas total cellular Cx43 remained unchanged. Our results suggest that the relative abundance of Cx43 and Cx40 is an important determinant of atrial impulse propagation in neonatal hearts, whereby dominance of Cx40 decreases and dominance of Cx43 increases local propagation velocity.

Electrotonic modulation of cardiac impulse conduction by myofibroblasts

Structural remodeling of the myocardium associated with mechanical overload or cardiac infarction is accompanied by the appearance of myofibroblasts. These fibroblast-like cells express alpha-smooth muscle actin (alphaSMA) and have been shown to express connexins in tissues other than heart. The present study examined whether myofibroblasts of cardiac origin establish heterocellular gap junctional coupling with cardiomyocytes and whether ensuing electrotonic interactions affect impulse propagation. For this purpose, impulse conduction characteristics (conduction velocity [theta] and maximal upstroke velocity [dV/dtmax]) were assessed optically in cultured strands of cardiomyocytes, which were coated with fibroblasts of cardiac origin. Immunocytochemistry showed that cultured fibroblasts underwent a phenotype switch to alphaSMA-positive myofibroblasts that expressed connexin 43 and 45 both among themselves and at contact sites with cardiomyocytes. Myofibroblasts affected theta and dV/dtmax in a cell density-dependent manner; a gradual increase of myofibroblast-to-cardiomyocyte ratios up to 7:100 caused an increase of both theta and dV/dtmax, which was followed by a progressive decline at higher ratios. On full coverage of the strands with myofibroblasts (ratio >20:100), theta fell <200 mm/s. This biphasic dependence of theta and dV/dtmax on myofibroblast density is reminiscent of "supernormal conduction" and is explained by a myofibroblast density-dependent gradual depolarization of the cardiomyocyte strands from -78 mV to -50 mV as measured using microelectrode recordings. These findings suggest that myofibroblasts, apart from their role in structural remodeling, might contribute to arrhythmogenesis by direct electrotonic modulation of conduction and that prevention of their appearance might represent an antiarrhythmic therapeutic target.

Gap junction channels and cardiac impulse propagation

The role of gap junction channels on cardiac impulse propagation is complex. This review focuses on the differential expression of connexins in the heart and the biophysical properties of gap junction channels under normal and disease conditions. Structural determinants of impulse propagation have been gained from biochemical and immunocytochemical studies performed on tissue extracts and intact cardiac tissue. These have defined the distinctive connexin coexpression patterns and relative levels in different cardiac tissues. Functional determinants of impulse propagation have emerged from electrophysiological experiments carried out on cell pairs. The static properties (channel number and conductance) limit the current flow between adjacent cardiomyocytes and thus set the basic conduction velocity. The dynamic properties (voltage-sensitive gating and kinetics of channels) are responsible for a modulation of the conduction velocity during propagated action potentials. The effect is moderate and depends on the type of Cx and channel. For homomeric-homotypic channels, the influence is small to medium; for homomeric-heterotypic channels, it is medium to strong. Since no data are currently available on heteromeric channels, their influence on impulse propagation is speculative. The modulation by gap junction channels is most prominent in tissues at the boundaries between cardiac tissues such as sinoatrial node-atrial muscle, atrioventricular node-His bundle, His bundle-bundle branch and Purkinje fibers-ventricular muscle. The data predict facilitation of orthodromic propagation.

[Gerodontology consultation in geriatric facilities: general health status (I)]

Dental undertreatment is often seen in the older population. This is particularly true for the elderly living in nursing homes and geriatric hospitals. The progression of chronic diseases results in loss of their independence. They rely on daily support and care due to physical or mental impairment. The visit of a dentist in private praxis becomes difficult or impossible and is a logistic problem. These elderly patients are often not aware of oral and dental problems or these are not addressed. The geriatric hospital Bern, Ziegler, has integrated dental care in the concept of physical rehabilitation of geriatric patients. A total of 139 patients received dental treatment in the years 2005/2006. Their mean age was 83 years, but the segment with > 85 years of age amounted to 46%. The general health examinations reveald multiple and complex disorders. The ASA classification (American Society of Anesthesiologists, Physical Status Classification System) was applied and resulted in 15% = P2 (mild systemic disease, no functional limitation), 47% = P3 (severe systemic disease, definite functional limitations) and 38% = P4 (severe systemic disease, constant threat to life). Eighty-seven of the patients exhibited 3 or more chronic diseases with a prevalence of cardiovascular diseases, musculoskelettal disorders and dementia. Overall the differences between men and women were small, but broncho-pulmonary dieseases were significantly more frequent in women, while men were more often diagnosed with dementia and depression. Verbal communication was limited or not possible with 60% of the patients due to cognitive impairment or aphasia after a stroke. Although the objective treatment need is high, providing dentistry for frail and geriatric patients is characterized by risks due to poor general health conditions, difficulties in communication, limitations in feasibility and lack of adequate aftercare. In order to prevent the problem of undertreatment, elderly independently living people should undergo dental treatment regularly and in time. Training of nurses and doctors of geriatric hospitals in oral hygiene should improve the awareness. A multidisciplinary assessment of geriatric patients should include the oral and dental aspect if they enter the hospital.

Embedding Moose Facilities Directly in IDEs

Moose is a powerful reverse engineering platform, but its facilities and means to analyze software are separated from the tools developers typically use to develop and maintain their software systems: development environments such as Eclipse, VisualWorks, or Squeak. In practice, this requires developers to work with two distinct environments, one to actually develop the software, and another one (e.g., Moose) to analyze it. We worked on several different techniques, using both dynamic and static analyzes to provide software analysis capabilities to developers directly in the IDE. The immediate availability of analysis tools in an IDE significantly increases the likelihood that developers integrate software analysis in their daily work, as we discovered by conducting user studies with developers. Finally, we identified several important aspect of integrating software analysis in IDEs that need to be addressed in the future to increase the adoption of these techniques by developers.