Primary reconstruction of open depressed skull fractures with titanium mesh

Open skull fractures have been traditionally managed in 2 stages: urgent craniotomy and elevation of the fracture with removal of contaminated bone, debridement, and delayed cranioplasty. Primary, single-stage repair of these injures has been said to entail risks such as infections. Recent experience, however, disproved these concerns.We used a primary single-stage reconstruction for patients presenting with open depressed skull fractures. All patients received antibiotic prophylaxis. The patients underwent elevation of the compound fracture and craniotomy if necessary. Debridement was performed, followed by skull reconstruction using a 0.6-mm titanium mesh.We present 5 consecutive male patients (age, 32.2 +/- 15.6 years) who underwent primary reconstruction of open depressed skull fractures. Clinical and radiologic follow-up was performed 2 months after surgery. The duration of the surgery was 2 +/- 1.6 hours. The size of the implanted mesh was 13 +/- 13.1 cm. No infection was detected in our series, with a follow-up period of 22 +/- 6.5 months (range, 16-29 months). The cosmetic result was defined in 4 patients as "excellent" and in 1 patient as "good."Primary reconstruction of open skull fractures with titanium mesh is feasible, safe, and cosmetically preferable than the conventional staged approach. The introduction into clinical practice can be warranted.

Prevention of delayed cerebral vasospasm by continuous intrathecal infusion of glyceroltrinitrate and nimodipine in the rabbit model in vivo

OBJECTIVE: Intrathecal bolus administration of nitric oxide donors and calcium channel antagonists has been proposed to reduce cerebral vasospasm (CVS) in animal subarachnoid hemorrhage (SAH) models. Intrathecal continuous administration of these substances for CVS prevention has not been extensively evaluated. This study compared the efficacy of continuous intrathecal infusions of the NO donor glyceroltrinitrate and nimodipine in preventing delayed CVS associated with SAH in an animal model in vivo. METHODS: New Zealand White rabbits were randomly assigned to six groups: no SAH/NaCl, no SAH/NO, no SAH/nimodipine, SAH/NaCl, SAH/NO, or SAH/nimodipine. Glyceroltrinitrate (GTN) at 0.5 microg/microl (0.5 microl/h) or nimodipine at 0.2 microg/microl (10 microl/h) or NaCl was continuously infused into the cisterna magna via an Alzet osmotic pump from day 0 to day 5 after injection of 1.0 ml autologous blood. The magnitude of spasm in the basilar artery was determined by comparison of pre- and posttreatment angiography and was calculated as proportional change in intraluminal diameter based on automatic measurements. RESULTS: A total of 55 experiments and 110 angiograms were performed. SAH was associated with vasoconstriction of the basilar artery (SAH/NaCl group 19.85+/-2.94%). Continuous intrathecal injection of GTN and nimodipine prevented SAH-induced CVS. There was significant prevention of CVS in animals treated with GTN (SAH/NO group 5.93+/-5.2%, n=11) and nimodipine (SAH/nimodipine group: 0.55+/-2.66%, n=9). There was no significant difference between the treatment groups and controls in prevention of CVS. CONCLUSIONS: This study demonstrates that prophylactic continuous intrathecal administration of either GTN or nimodipine equally prevents SAH-associated CVS in an animal model.

Monitoring protein-protein interactions between the mammalian integral membrane transporters and PDZ-interacting partners using a modified split-ubiquitin membrane yeast two-hybrid system

PDZ-binding motifs are found in the C-terminal tails of numerous integral membrane proteins where they mediate specific protein-protein interactions by binding to PDZ-containing proteins. Conventional yeast two-hybrid screens have been used to probe protein-protein interactions of these soluble C termini. However, to date no in vivo technology has been available to study interactions between the full-length integral membrane proteins and their cognate PDZ-interacting partners. We previously developed a split-ubiquitin membrane yeast two-hybrid (MYTH) system to test interactions between such integral membrane proteins by using a transcriptional output based on cleavage of a transcription factor from the C terminus of membrane-inserted baits. Here we modified MYTH to permit detection of C-terminal PDZ domain interactions by redirecting the transcription factor moiety from the C to the N terminus of a given integral membrane protein thus liberating their native C termini. We successfully applied this "MYTH 2.0" system to five different mammalian full-length renal transporters and identified novel PDZ domain-containing partners of the phosphate (NaPi-IIa) and sulfate (NaS1) transporters that would have otherwise not been detectable. Furthermore this assay was applied to locate the PDZ-binding domain on the NaS1 protein. We showed that the PDZ-binding domain for PDZK1 on NaS1 is upstream of its C terminus, whereas the two interacting proteins, NHERF-1 and NHERF-2, bind at a location closer to the N terminus of NaS1. Moreover NHERF-1 and NHERF-2 increased functional sulfate uptake in Xenopus oocytes when co-expressed with NaS1. Finally we used MYTH 2.0 to demonstrate that the NaPi-IIa transporter homodimerizes via protein-protein interactions within the lipid bilayer. In summary, our study establishes the MYTH 2.0 system as a novel tool for interactive proteomics studies of membrane protein complexes.

Surgical approach for synovial cyst of the atlantoaxial joint: a case report and review of the literature

STUDY DESIGN: Case report and review of the literature. OBJECTIVE: We describe the first case of a synovial cyst arising from pseudarthrosis of a previous dens fracture. The literature is reviewed and etiological, diagnostic, and therapeutic options of atlantoaxial cysts are discussed. SUMMARY OF BACKGROUND DATA: Symptomatic synovial cysts of the atlantoaxial joint are rare. To the authors' knowledge only 24 cases have been reported.A 60-year-old patient presented with bilateral hand numbness, quadrihyperreflexia, and gait deterioration. Magnetic resonance imaging of the cervical spine disclosed a cystic mass located at the transverse ligament of dens axis causing bulbomedullary compression. METHODS: Surgery was performed via transoral image guided approach. The ventral atlas arch, dens, transverse ligament, tectorial membrane, and the compressing cyst were removed, followed by a C0-C3 fusion. RESULTS: Two months postsurgery the patient recovered completely from the cervical myelopathy with transient remnant dysparesthesia of the finger tips. CONCLUSION: Magnetic resonance imaging findings are not specific enough to establish a preoperative diagnosis. Radical resection via image-guided transoral route followed by posterior fusion allows complete resection of the cystic lesion and results in excellent long-term decompression.

Norepinephrine-induced hypertension dilates vasospastic basilar artery after subarachnoid haemorrhage in rabbits

BACKGROUND: Vasopressor-induced hypertension is routinely indicated for prevention and treatment of cerebral vasospasm (CVS) after subarachnoid haemorrhage (SAH). Mechanisms underlying patients' clinical improvement during vasopressor-induced hypertension remain incompletely understood. The aim of this study was to evaluate angiographic effects of normovolaemic Norepinephrine (NE)-induced hypertension therapy on the rabbit basilar artery (BA) after SAH. METHODS: Cerebral vasospasm was induced using the one-haemorrhage rabbit model; sham-operated animals served as controls. Five days later the animals underwent follow-up angiography prior to and during NE-induced hypertension. Changes in diameter of the BA were digitally calculated in mean microm +/- SEM (standard error of mean). FINDINGS: Significant CVS of 14.2% was documented in the BA of the SAH animals on day 5 compared to the baseline angiogram on day 0 (n = 12, p < 0.01), whereas the BA of the control animals remained statistically unchanged (n = 12, p > 0.05). During systemic administration of NE, mean arterial pressure increased from 70.0 +/- 1.9 mmHg to 136.0 +/- 2.1 mmHg in the SAH group (n = 12, p < 0.001) and from 72.0 +/- 3.1 to 137.8 +/- 1.3 in the control group (n = 12, p < 0.001). On day 5 after SAH, a significant dilatation of the BA in response to norepinephrine could be demonstrated in both groups. The diameter of the BA in the SAH group increased from 640.5 +/- 17.5 microm to 722.5 +/- 23.7 microm (n = 12, p < 0.05; ). In the control group the diameter increased from 716.8 +/- 15.5 microm to 779.9 +/- 24.1 microm (n = 12, p < 0.05). CONCLUSION: This study demonstrated that NE-induced hypertension causes angiographic dilatation of the BA in the SAH rabbit model. Based on these observations, it can be hypothesised that clinical improvement during vasopressor-induced hypertension therapy after SAH might be explained with cerebral vasodilatation mechanisms that lead to improvement of cerebral blood flow.

Feasibility and safety of same-day home discharge after radiofrequency catheter ablation

Interventional cardiology in a day-case setting might reduce logistic constraints on hospital resources. However, in contrast with coronary angioplasty, few data support the feasibility and safety of radiofrequency catheter ablation (RCA). The aim of this prospective, multicenter cohort study was to evaluate the feasibility and safety of RCA in 1,342 patients (814 men; mean age 57 +/- 17 years) considered eligible for ambulatory RCA, according to specific set of criteria, for common atrial flutter (n = 632), atrioventricular nodal reentrant tachycardia (n = 436), accessory pathways (n = 202), and atrial tachycardia (n = 72). Patients suitable for early discharge (4 to 6 hours after uncomplicated RCA) were scheduled for 1-month follow-up. Predictive factors for delayed complications were studied by multivariate analysis. Of the 1,342 enrolled patients, 1,270 (94.6%) were discharged the same day and followed for 1 month; no deaths occurred, and the readmission rate was 0.79% (95% confidence interval 0.30% to 1.27%). Six patients had significant puncture complications, 2 presented with symptomatic delayed pulmonary embolism, and 2 had new onset of poorly tolerated atrial flutter. None of these complications was life threatening. Multivariate analysis did not identify any significant independent predictors for delayed complications. In conclusion, these data suggest that same-day discharge after uncomplicated RCA for routine supraventricular arrhythmias is safe and may be applicable in clinical practice. This approach is known to be associated with significant patient satisfaction and cost savings and can be considered a first-line option in most patients who undergo routine ablation procedures.

Elevated level of endothelin-1 in cerebrospinal fluid and lack of nitric oxide in basilar arterial plasma associated with cerebral vasospasm after subarachnoid haemorrhage in rabbits

BACKGROUND: The role of endothelin-1 (ET-1) and nitric oxide (NO) as two important mediators in the development of cerebral vasospasm (CVS) after subarachnoid haemorrhage (SAH) is controversial. The objective of this study was to determine whether local levels of ET-1 and NO in cerebral arterial plasma and/or in cerebrospinal fluid (CSF) are associated with the occurrence of CVS after SAH. METHODS: CVS was induced using the one-haemorrhage rabbit model and confirmed by digital subtraction angiography of the rabbits' basilar artery on day 5. Prior to sacrifice, local CSF and basilar arterial plasma samples were obtained by a transclival approach to the basilar artery. Systemic arterial plasma samples were obtained. ET-1 levels were determined by immunometric technique (pg/ml +/- SEM) and total nitrate/nitrite level spectrophotometrically (micromol/l +/- SEM). FINDINGS: Angiographic CVS was documented after SAH induction (n = 12, P < 0.05). The ET-1 level in CSF was significantly elevated by 27.3% to 0.84 +/- 0.08 pg/ml in SAH animals (n = 7) in comparison to controls (0.66 +/- 0.04 pg/ml, n = 7, P < 0.05). There was no significant difference in ET-1 levels in systemic and basilar arterial plasma samples of SAH animals compared to controls. A significant lack of local NO metabolites was documented in basilar arterial plasma after SAH (36.8 +/- 3.1 micromol/l, n = 6) compared to controls (61.8 +/- 6.2 micromol/l, n = 6, P < 0.01). CONCLUSION: This study demonstrates that an elevated ET-1 level in CSF and local lack of NO in the basilar arterial plasma samples are associated with CVS after experimental SAH.

High-resolution three-dimensional 3 T magnetic resonance angiography for the evaluation of experimental aneurysm in the rabbit

OBJECTIVE: The standard technique of two-dimensional intra-arterial digital subtraction angiography (2D-DSA) for the imaging of experimental rabbit aneurysms is invasive and has considerable surgical risks. Therefore, minimally invasive techniques ideally providing three-dimensional imaging for intervention planning and follow-up are needed. This study evaluates the feasibility and quality of three-dimensional 3-T magnetic resonance angiography (3D-3T-MRA) and compares 3D-3T-MRA with 2D-DSA in experimental aneurysms in the rabbit. METHOD: Three microsurgically created aneurysms in three rabbits were evaluated using 2D-DSA and 3D-3T-MRA. Imaging of the aneurysms was performed 2 weeks after creation using 2D-DSA and contrast-enhanced (CE) MRA. Measurements included aneurysm dome (length and width) and aneurysm neck. Aneurysm volumes were determined using CE-MRA. RESULTS: The measurements of the aneurysms' dimensions and the evaluation of vicinity vessels with both techniques showed a good correlation. The mean aneurysm length, aneurysm width and neck width measured with DSA (6.9, 4.1 and 2.8 mm, respectively) correlated with the measurements performed in 3D-3T-MRA (6.9, 4 and 2.5 mm, respectively). The mean aneurysm volumes measured with CE-MRA was 46.7 mm(3). CONCLUSION: 3D-3T CE-MRA is feasible and less invasive and is a safer imaging alternative to DSA for experimental aneurysm. Additionally, aneurysm technique this precise offers the possibility of repetitive 3D aneurysm volumetry for long-term follow-up studies after endovascular aneurysm occlusion.

GABARAP deficiency modulates expression of NaPi-IIa in renal brush-border membranes

Renal reabsorption of inorganic phosphate (P(i)) is mainly mediated by the Na(+)-dependent P(i)-cotransporter NaPi-IIa that is expressed in the brush-border membrane (BBM) of renal proximal tubules. Regulation and apical expression of NaPi-IIa are known to depend on a network of interacting proteins. Most of the interacting partners identified so far associate with the COOH-terminal PDZ-binding motif (TRL) of NaPi-IIa. In this study GABA(A) receptor-associated protein (GABARAP) was identified as a novel interacting partner of NaPi-IIa applying a membrane yeast-two-hybrid system (MYTH 2.0) to screen a mouse kidney library with the TRL-truncated cotransporter as bait. GABARAP mRNA and protein are present in renal tubules, and the interaction of NaPi-IIa and GABARAP was confirmed by using glutathione S-transferase pulldowns from BBM and coimmunoprecipitations from transfected HEK293 cells. Amino acids 36-68 of GABARAP were identified as the determinant for the described interaction. The in vivo effects of this interaction were studied in a murine model. GABARAP(-/-) mice have reduced urinary excretion of P(i), higher Na(+)-dependent (32)P(i) uptake in BBM vesicles, and increased expression of NaPi-IIa in renal BBM compared with GABARAP(+/+) mice. The expression of Na(+)/H(+) exchanger regulatory factor (NHERF)1, an important scaffold for the apical expression of NaPi-IIa, is also increased in GABARAP(-/-) mice. The absence of GABARAP does not interfere with the regulation of the cotransporter by either parathyroid hormone or acute changes of dietary P(i) content.

JExample: Exploiting Dependencies Between Tests to Improve Defect Localization

To quickly localize defects, we want our attention to be focussed on relevant failing tests. We propose to improve defect localization by exploiting dependencies between tests, using a JUnit extension called JExample. In a case study, a monolithic white-box test suite for a complex algorithm is refactored into two traditional JUnit style tests and to JExample. Of the three refactorings, JExample reports five times fewer defect locations and slightly better performance (-8-12\%), while having similar maintenance characteristics. Compared to the original implementation, JExample greatly improves maintainability due the improved factorization following the accepted test quality guidelines. As such, JExample combines the benefits of test chains with test quality aspects of JUnit style testing.

Object-Oriented Reengineering Patterns

The rapid growth of object-oriented development over the past twenty years has given rise to many object-oriented systems that are large, complex and hard to maintain. Object-Oriented Reengineering Patterns addresses the problem of understanding and reengineering such object-oriented legacy systems. This book collects and distills successful techniques in planning a reengineering project, reverse-engineering, problem detection, migration strategies and software redesign. The material in this book is presented as a set of "reengineering patterns" --- recurring solutions that experts apply while reengineering and maintaining object-oriented systems. The principles and techniques described in this book have been observed and validated in a number of industrial projects, and reflect best practice in object-oriented reengineering.

"...all diese fingierten, notierten, in meinem Kopf ungefähr wieder zusammengesetzten Ichs". Autobiographie und Autofiktion

Dass jede literarische Selbstdarstellung fiktionale Elemente beinhaltet, ist in der gegenwärtigen Autobiographie-Diskussion unbestritten. Mit dem von Serge Doubrovsky geprägten Terminus »Autofiktion« hat sich die Forschung verstärkt literarischen Texten zugewendet, die fiktionales und faktuales Erzählen der eigenen Biographie mehr oder minder offensichtlich vermischen und so die Problematik literarischer Selbstthematisierung reflektieren. Ausgehend von der theoretischen Diskussion um Autobiographie und Autofiktion werden Texte und Textentwürfe von Robert Walser, Annemarie Schwarzenbach, Paul Nizon, Friedrich Dürrenmatt und Urs Widmer mit ihren je eigenen und nicht selten eigenwilligen Konzepten des literarischen Umgangs mit der Biographie untersucht. Mit Beiträgen von Peter Gasser, Wolfram Groddeck, Lucas Marco Gisi, Heidy Margrit Müller, Ulrich Weber, Reto Sorg, Elio Pellin und Irmgard Wirtz.