Efficacy and safety of intravenous amiodarone for incessant tachycardias in infants

Amiodarone is an effective anti-arrhythmic agent for the treatment of supraventricular and ventricular tachycardias. The safety and efficacy of intravenous amiodarone has been described in adults and children but only to a limited extent in infants. The purpose of this study was to evaluate the safety and efficacy of intravenous amiodarone in infants. Between February 1994 and June 2001, 23 infants with a median age of 8 days (range 1-300 days) with life-threatening incessant tachycardias (17 supraventricular, 6 ventricular) were treated with intravenous amiodarone as single anti-arrhythmic agent. At presentation, 22 infants were haemodynamically unstable. Amiodarone was given as an intravenous loading dose of 5mg/kg over 1h followed by an intravenous maintenance dose of 5µg/kg per min with stepwise increase up to 25µg/kg per min until arrhythmia control or side-effects occurred. Amiodarone was effective in 19 infants, partially effective in three and ineffective in one infant. The median time until arrhythmia control was 24h (range 1-96h) and the median maintenance dosage 15µg/kg per min (range 5-26µg/kg per min). Electrophysiological side-effects necessitating dose reduction comprised of sinus bradycardia in two patients. Hypotension in one patient resolved after dose diminution. Neurological side-effects consisted of choreatic movements in one infant, which resolved over time. Amiodarone administration was stopped in one patient with elevated liver enzymes. Conclusion:intravenous amiodarone is a safe and effective therapy for life-threatening incessant tachycardias in infant

Resource-Based Accountability: A Case Study on Multiple Accountability Relations in an Economic Development Nonprofit

In economic development nonprofits, the disparity between the nonprofit's, its donor's and the poor's expectations concerning poverty alleviation has been identified as the main reason for ineffective aid delivery. The study at hand contributes to this discussion by following this question: How do the nonprofit, its donors, the supported SMEs, and the poor refer to the nonprofit's mission of poverty alleviation when negotiating accountability? To answer this question, the study follows the literature on accountability and resource dependency and presents results of an empirical case study on multiple accountability relations between a donor, a development aid nonprofit, its supported SMEs, and the poor living in the environment of the supported SMEs. The results show a pattern we call "resource-based accountability.” This pattern is constituted by the observation that most of the stakeholders tried to meet the expectations of the resource owners with respect to the resource owner's understanding of successful poverty alleviation. Finally, the paper introduces a hypothesis for further studies

Temporary Kirschner Wire Ankle Transfixation and Delayed ORIF: A Staged Operative Treatment for Closed Ankle Fractures with Tibiotalar Dislocations and Soft-Tissue Damage

Abstract : Background and Purpose: : Immediate ORIF (open reduction and internal fixation) is the treatment of choice for displaced ankle fractures. However, definitive treatment may have to be delayed due to compromised soft tissues. The value of temporary Kirschner wire ankle transfixation with staged ORIF for closed displaced ankle fractures with tibiotalar dislocations was determined. Patients and Methods: : In this retrospective case series (1997-2001), 92 patients (mean age 54 years, range 20-86 years) who underwent a staged procedure for isolated and closed displaced ankle fractures with tibiotalar dislocations were studied. Patients were primarily treated by means of immediate closed reduction. For stable fractures and adequate soft tissues a split plaster cast was applied (n = 50). K-wire transfixation was performed for unstable fracture-dislocations and/or critical soft tissues (n = 42). All patients underwent delayed ORIF after recovery of the soft tissues. Results: : In the K-wire group (KWG), local complication rate was 7%. Mean operating time was 30 min (5-65 min). In the plaster cast group (PCG), local complication rate was 10% (p = 0.72, not significant). Three redislocated ankles (6%) had to be transfixed secondarily. A higher grade of soft-tissue injuries in the KWG (p < 0.05) resulted in a longer time interval between primary treatment and staged ORIF (7 vs. 5 days; p < 0.05) and a longer hospital stay (19 vs. 17 days; p < 0.05) for the KWG. Conclusion: : Temporary K-wire ankle transfixation is an effective method for initial treatment of closed displaced ankle fractures with tibiotalar dislocation, if ORIF has to be delayed and immobilization in a split plaster cast is not suitable. Retention is reliable with a low complication rat

Bacteria-on-a-bead: probing the hydrodynamic interplay of dynamic cell appendages during cell separation

Surface attachment of bacteria is the first step of biofilm formation and is often mediated and coordinated by the extracellular appendages, flagellum and pili. The model organism Caulobacter crescentus undergoes an asymmetric division cycle, giving rise to a motile "swarmer cell" and a sessile "stalked cell", which is attached to the surface. In the highly polarized predivisional cell, pili and flagellum, which are assembled at the pole opposite the stalk, are both activated before and during the process of cell separation. We explored the interplay of flagellum and active pili by growing predivisional cells on colloidal beads, creating a bacteria-on-a-bead system. Using this set-up, we were able to simultaneously visualize the bacterial motility and analyze the dynamics of the flagellum and pili during cell separation. The observed activities of flagellum and pili at the new cell pole of the predivisional cell result in a cooperating interplay of the appendages during approaching and attaching to a surface. Even in presence of a functioning flagellum, pili are capable of surface attachment and keeping the cell in position. Moreover, while flagellar rotation decreases the average attachment time of a single pilus, it increases the overall attachment rate of pili in a synergetic manner

Second messenger-mediated tactile response by a bacterial rotary motor

When bacteria encounter surfaces, they respond with surface colonization and virulence induction. The mechanisms of bacterial mechanosensation and downstream signaling remain poorly understood. Here, we describe a tactile sensing cascade in Caulobacter crescentus in which the flagellar motor acts as sensor. Surface-induced motor interference stimulated the production of the second messenger cyclic diguanylate by the motor-associated diguanylate cyclase DgcB. This led to the allosteric activation of the glycosyltransferase HfsJ to promote rapid synthesis of a polysaccharide adhesin and surface anchoring. Although the membrane-embedded motor unit was essential for surface sensing, mutants that lack external flagellar structures were hypersensitive to mechanical stimuli. Thus, the bacterial flagellar motor acts as a tetherless sensor reminiscent of mechanosensitive channels

In situ structure of the Caulobacter crescentus flagellar motor and visualization of binding of a CheY-homolog

Bacterial flagellar motility is controlled by the binding of CheY proteins to the cytoplasmic switch complex of the flagellar motor, resulting in changes in swimming speed or direction. Despite its importance for motor function, structural information about the interaction between effector proteins and the motor are scarce. To address this gap in knowledge, we used electron cryotomography and subtomogram averaging to visualize such interactions inside Caulobacter crescentus cells. In C. crescentus, several CheY homologs regulate motor function for different aspects of the bacterial lifestyle. We used subtomogram averaging to image binding of the CheY family protein CleD to the cytoplasmic Cring switch complex, the control center of the flagellar motor. This unambiguously confirmed the orientation of the motor switch protein FliM and the binding of a member of the CheY protein family to the outside rim of the C ring. We also uncovered previously unknown structural elaborations of the alphaproteobacterial flagellar motor, including two novel periplasmic ring structures, and the stator ring harboring eleven stator units, adding to our growing catalog of bacterial flagellar diversity

Fibrin versus polyethylene glycol sealant: an experimental study in rabbits

Fibrin glue has been applied universally in general surgery as an adhesive, hemostatic, or embolizing agent. In reconstructive surgery, fibrin has been used mainly for nerve and microvascular repair or as a substitute for sutures in skin closure and skin grafting. Another area of increasing use is in face-lift surgery, where the goal is to improve hemostasis on the raw surfaces and to discourage the occurrence of major hematomas. However, as most components of the fibrin glue are derived from human or bovine plasma, they may cause allergic reactions and transmit infectious agents such as hepatitis or AIDS virus, or prions such as the Creutzfeldt-Jakob disease agent. With these risks in mind, we tested polyethylene glycol (PEG) sealant, a recently introduced and purely synthetic vascular sealant, as an alternative to fibrin glue. A 2 × 2cm subcutaneous pocket was created on the dorsal thighs of ten New Zealand White rabbits by an incision medial to the sciatic vein. The pockets were randomly filled with either 0.2ml of thawed fibrin glue or PEG sealant. After the operation, the thighs were inspected macroscopically for hematoma, seroma, or granuloma formation. Eleven weeks later, the animals were killed, and the fibrin and polyethylene glycol-filled pockets were harvested en bloc with the overlying skin and processed for histological examination. A swelling, viewed macroscopically, was visible at the experimental site in three thighs of the fibrin group, but in none of the PEG group. Only two specimens of the fibrin group and five specimens of the PEG group showed no signs of inflammation. All other specimens revealed signs of chronic or granulomatous inflammation, with no significant difference between the groups. This experimental study showed that 11weeks after application of either fibrin or PEG sealant, signs of chronic or even granulomatous inflammation were detectable in 2/3 of the specimens in the fibrin group and in approximately 50% of the specimens in the PEG group. Beyond the comparable potential of both sealants to induce inflammatory tissue reactions, PEG sealant has some notable advantages as it is purely synthetic and therefore carries no risk of transmission of viral pathogens or prions. The combination of this safety profile, the ease of application, and the consistently good reported hemostatic results obtained with PEG sealant makes it an interesting alternative to fibrin glue in plastic surger

Crystal structure of Caulobacter crescentus polynucleotide phosphorylase reveals a mechanism of RNA substrate channelling and RNA degradosome assembly

Polynucleotide phosphorylase (PNPase) is an exoribonuclease that cleaves single-stranded RNA substrates with 3′–5′ directionality and processive behaviour. Its ring-like, trimeric architecture creates a central channel where phosphorolytic active sites reside. One face of the ring is decorated with RNA-binding K-homology (KH) and S1 domains, but exactly how these domains help to direct the 3′ end of single-stranded RNA substrates towards the active sites is an unsolved puzzle. Insight into this process is provided by our crystal structures of RNA-bound and apo Caulobacter crescentus PNPase. In the RNA-free form, the S1 domains adopt a ‘splayed’ conformation that may facilitate capture of RNA substrates. In the RNA-bound structure, the three KH domains collectively close upon the RNA and direct the 3′ end towards a constricted aperture at the entrance of the central channel. The KH domains make non-equivalent interactions with the RNA, and there is a marked asymmetry within the catalytic core of the enzyme. On the basis of these data, we propose that structural non-equivalence, induced upon RNA binding, helps to channel substrate to the active sites through mechanical ratcheting. Structural and biochemical analyses also reveal the basis for PNPase association with RNase E in the multi-enzyme RNA degradosome assembly of the α-proteobacteria

Do Predictors Exist for a Successful Withdrawal of Preoperative Prostaglandin E1 from Neonates with d-Transposition of the Great Arteries and Intact Ventricular Septum?

Prostaglandin E1 (PGE1) is given to neonates with d-transposition of the great arteries (d-TGA) to reduce cyanosis by reopening and maintaining the patency of the ductus arteriosus. To avoid side effects, this medication can be stopped for hemodynamically stable patients after balloon atrial septostomy (BAS). A consecutive series of neonates with d-TGA and an intact ventricular septum (IVS) presenting from 2000 through 2005 was analyzed retrospectively to search for side effects of PGE1 and to identify predictors for a safe preoperative withdrawal. The medication was stopped for hemodynamically stable patients with transcutaneous oxygen saturations higher than 80% after BAS and reinitiated for patients with an oxygen saturation lower than 65%. Patients successfully weaned were compared with those who had failed weaning in terms of atrial septal defect (ASD) size, ductus arteriosus size, and the transcutaneous oxygen saturation. Prostaglandin E1 was initiated for all 43 neonates with d-TGA. The median maintenance dose of PGE1 was 0.00625μg/kg/min (range, 0.00313-0.050μg/kg/min) for a median duration of 6days (range, 1-12days). For 16 patients, PGE1 was preoperatively withdrawn but then had to be reinitiated for 7 of the 16 patients. No predictors for a successful weaning of PGE1 were found based on ASD size, ductus arteriosus size, or oxygen saturation. The adverse effects of PGE1 were apnea in 10 patients and fever in 19 patients. Neither seizures nor necrotizing enterocolitis was documented. Prostaglandin E1 was successfully withdrawn for a minority of hemodynamically stable patients with d-TGA. No predictors for a successful weaning could be identified. Because apnea and fever are common side effects, withdrawal of PGE1 after BAS may improve patient safety and comfort. In this patient group, if PGE1 withdrawal was not well tolerated, it could be safely reinitiated. There were no serious side effects of PGE