Binding by calmodulin is coupled to transient unfolding of the third FF domain of Prp40A.

Human pre-mRNA processing protein 40 homolog A (hPrp40A) is a splicing factor that interacts with the Huntington's disease protein huntingtin (Htt). Evidence has accumulated that both Htt and hPrp40A are modulated by the intracellular Ca2+ sensor calmodulin (CaM). Here we report characterization of the interaction of human CM with the third FF domain (FF3 ) of hPrp40A using calorimetric, fluorescence and structural approaches. Homology modeling, differential scanning calorimetry and small angle X-ray scattering (SAXS) data show FF3 forms a folded globular domain. CaM was found to bind FF3 in a Ca2+ -dependent manner with a 1:1 stoichiometry and a dissociation constant (Kd ) of 25 ± 3 µM at 25°C. NMR studies showed that both domains of CaM are engaged in binding and SAXS analysis of the FF3 -CaM complex revealed CaM occupies an extended configuration. Analysis of the FF3 sequence showed that the anchors for CaM binding must be buried in its hydrophobic core, suggesting that binding to CaM requires unfolding of FF3 . Trp anchors were proposed based on sequence analysis and confirmed by intrinsic Trp fluorescence of FF3 upon binding of CaM and substantial reductions in affinity for Trp-Ala FF3 mutants. The consensus model of the complex showed that binding to CaM binding occurs to an extended, non-globular state of the FF3 , consistent with coupling to transient unfolding of the domain. The implications of these results are discussed in the context of the complex interplay of Ca2+ signaling and Ca2+ sensor proteins in modulating Prp40A-Htt function.

[New aspects in surgery of the nasal tip]. / Neue Aspekte in der Nasenspitzenchirurgie.

The creation of both a functionally and aesthetically pleasing nasal tip contour is demanding and depends on a variety of parameters. Typically, procedures are performed with emphasis on narrowing the nasal tip structure. Excisional techniques alone inevitably lead to reduction in skeletal support and are often prone to unpredictable deformities. But long-term results of classical suture techniques have also shown unfavorable outcomes. Particularly pinching of the alae and displacement of the caudal margin of the lateral crus below the cephalic margin belong in this category. A characteristic loss of structural continuity between the domes and the alar lobule and an undesirable shadowing occur. These effects lead to an unnatural appearance of the nasal tip and frequently to impaired nasal breathing. Stability and configuration of the alar cartilages alone do not allow for an adequate evaluation of the nasal tip contour. Rather a three-dimensional approach is required in order to describe all nasal tip structures. Especially the rotational angle of the alar surface as well as the position of the lateral crus in relation to the cranial septum should be considered in the three-dimensional analysis. Taking the various parameters into account the authors present new aspects in nasal tip surgery which contribute to the creation of a functionally and aesthetically pleasing as well as durable nasal tip contour.

[Flaring spreader flaps and upper lateral advancement. Modified techniques in the reconstruction of the internal nasal valve]. / "Flaring spreader flaps" und "upper lateral advancement". Modifizierte Techniken zur Rekonstruktion der inneren Nasenklappe.

BACKGROUND: A collapse of the internal nasal valve and the formation of an inverted-V deformity represent common findings following dorsal hump removal in rhinoplasty procedures. Spreader grafts are considered as standard both in the prevention and treatment of such undesirable outcomes. The authors introduce modified surgical concepts using flaring spreader flaps and the upper lateral advancement technique to reconstruct the internal nasal valve. METHODS: After mobilization of the mucosa and separation of the upper lateral cartilages from the septum also their attachments to the nasal bones are released. The cartilages then are rotated as spreader flaps into the area of the internal nasal valve and can be used as a replacement for conventional spreader grafts. By crucial modifications of commonly applied suture techniques both the contour and airway are improved. The upper lateral advancement technique is used in cases of already present inverted-V deformities. The upper lateral cartilages are mobilized in a similar fashion and serve as attachments to usual spreader grafts. RESULTS: Flaring spreader flaps have been used in 164 patients undergoing primary rhinoplasty procedures for dorsal hump removals, the treatment of tension noses as well as deviated noses. Postoperatively all cases showed an adequate width of the middle nasal vault and pleasant dorsal aesthetic lines. No signs of an inverted-V deformity or a collapse of the internal nasal valve were present. Nasal breathing was considered significantly improved. The upper lateral advancement technique was applied in 9 patients with a present inverted-V deformity after previous rhinoplasties. During the following revision procedures an adequate reconstruction of the middle nasal vault as well as a subjectively improved airway was achieved in all cases. CONCLUSION: Both flaring spreader flaps and the upper lateral advancement technique represent reliable methods in the reconstruction of the internal nasal valve and treatment of inverted-V deformities. Moreover, flaring spreader flaps can be considered as an appropriate alternative to conventional spreader grafts in patients with only small amounts of cartilage available.

[Stapes surgery : first experiences with the new Soft-CliP piston]. / Steigbügelchirurgie : Erste Erfahrungen mit dem Einsatz des neuen Soft-CliP(R)-Pistons.

BACKGROUND: The first hearing results with a new stapes prosthesis with clip function (Soft-CliP(R) piston) are presented. PATIENTS AND METHODS: This new prosthesis was used in 15 patients (mean age 45.2 years; range 21-63 years) undergoing routine stapes surgery. Soft-CliP(R) piston prostheses with a shaft diameter of 0.4 mm and a length ranging from 4.25 mm to 5.5 mm were used. Postoperative audiological testing and measurement of the air-bone gap were performed after an average of 47.3 days and compared with the preoperative values. RESULTS: The median observed postoperative air-bone gap (ABG) was 8.33 dB +/-4.16 dB. All patients had less than 20 dB ABG and in 53.3% of cases was less than 10 dB. The operating time showed a clear difference between the left (66.5 min +/-37.79 min) and right ears (47.2 min +/-11.08 min). DISCUSSION: This new prosthesis design greatly facilitates a very difficult step in stapes surgery, the prosthesis fixation to the incus. The first postoperative hearing results are very promising but long-term results in a larger group of patients are still pending.

Management of paediatric sinonasal rhabdomyosarcoma.

BACKGROUND AND AIM: Rhabdomyosarcoma is the commonest malignant tumour of the nose and paranasal sinuses in the paediatric population. Due to its rarity and largely unknown biological behaviour, the treatment of this tumour is complex and controversial. We present the results of multimodality treatment of paediatric sinonasal rhabdomyosarcoma, and we explore the role of surgery in the management of this malignancy. METHODS: We retrospectively reviewed the records of 14 patients (median age 7.5 years) with sinonasal rhabdomyosarcoma. Six patients underwent major surgery with post-operative chemoradiation. Eight patients received multi-agent chemotherapy and radiotherapy. The mean follow-up time was 58 months (range seven to 276 months). RESULTS: The five-year overall survival rates for all patients and for the surgery group were 53.9 and 83.3 per cent, respectively. All patients with alveolar rhabdomyosarcoma had a poor prognosis, with a median survival time of 17 months. Intracranial extension and an age greater than 10 years were also associated with an unfavourable outcome. Non- or partial responders to initial chemoradiation died within a year of diagnosis. CONCLUSIONS: Management of paediatric rhabdomyosarcoma requires a combination of chemotherapy, radiotherapy and surgery. Primary chemoradiotherapy is the established treatment approach for advanced tumours. Early stage tumours with favourable histology can be treated successfully with radical surgery, provided that function and cosmetic appearance are preserved.

[Soft tissue navigation and image-guided removal of foreign bodies in head and neck surgery]. / Weichteilnavigation im Kopf-Hals-Bereich und navigierte Fremdkörperentfernung.

BACKGROUND: Soft tissue navigation has traditionally been neglected in computer-aided surgery (CAS) because of unpredictable margins of error. In our study, we examined clinical cases in which standard CAS was applied in soft tissue surgery in the head and neck region. Its extended applicability, margins of error, and general performance are described and discussed. MATERIALS AND METHODS: CAS was applied in surgical procedures for six patients. Five patients had foreign bodies in the head and neck region, and one patient displayed uncertain cervical lymph node enlargement. An optoelectrical navigation system (VectorVision(2), BrainLAB) was used in all cases. RESULTS: Using CAS, 10 out of 11 total foreign bodies were identified. Only one glass splinter attached to the eyeball could not be detected by the navigation system. One glass splinter that was deeply buried within the sphenoid bone was easily found but was left untouched. The parapharyngeal lymph node was identified and extracted in a minimally invasive transpalatinal approach. CONCLUSIONS: Soft tissue navigation was successfully applied in all but one case; the success was due to the altered demands in soft tissue navigation as opposed to skull-base surgery. Easy identification of foreign bodies and lymph nodes was possible in the soft tissues of the head and neck, with an acceptable margin of error.

Trocar-site hernia as a typical postoperative complication of minimally invasive surgery among preschool children.

BACKGROUND: Minimally invasive surgery (MIS) in preschool children (<5 years of age) is not common yet, and few reports evaluating typical complications are available. Trocar site hernias are well described in adult patients but also have been reported for preschool children. The goal of our study was to determine incidence and relevance of trocar site hernias as complications of minimally invasive surgery in preschool children. METHODS: Retrospective analysis of all pediatric patients who underwent minimally invasive surgery at a single institution. Review of the literature. RESULTS: Trocar site hernias are significantly more frequent in preschool children than in older ones (p = 0.006). Complication rates at all are not significantly different. Trocar site hernias in infants are mainly of type 3 (omental protrusion) and occur within the first postoperative week. CONCLUSION: Meticulous suturing of all layers (particularly the peritoneum) even in small incisions (2 mm) is recommended to prevent omental protrusion at trocar site in children up to 5 years of age.

[First experiences with a new nickel-titanium piston with a shape memory feature]. / Einsatz eines Nickel-Titan-Piston mit Memory-Eigenschaften: Erster Erfahrungsbericht.

BACKGROUND: The aim of this study was to describe a new stapes prosthesis with memory characteristics for wire crimping (SMart-Piston). PATIENTS AND METHODS: This technique was used in 15 patients (mean age 43.4 years; range 28-71) undergoing routine stapes surgery. SMart-Piston prostheses with a shaft diameter of 0.5 mm and length ranging from 4.25-4.5 mm were used. Heat induced wire crimping was performed by CO2 laser in five patients, and by bipolar diathermy forceps in ten patients. In 15 patients, postoperative audiological testing was performed at an average 21.9 days and in another 10 again after 435 days following surgery. RESULTS: The median observed air-bone-gap (ABG) postoperatively was 8.7 dB+/-7.7 dB. A total of 73% of all patients had an ABG of 10 dB or less, and all patients had less than 20 dB. In the ten patients controlled after 435 days, the ABG was 4.4 dB+/-2.4 dB. It was lower than 10 dB in all individuals. DISCUSSION: A critical point in every stapes surgery, the prosthesis fixation to the incus, is greatly facilitated by this novel technique. Long-term results in a larger group of patients are pending.

Leptonic and charged kaon decay modes of the phi meson measured in heavy-ion collisions at the CERN super proton synchrotron.

We report on results of a measurement of meson production in central Pb-Au collisions at E(lab) = 158A GeV. For the first time in the history of high energy heavy-ion collisions, phi mesons were reconstructed both in the K+K- and the dilepton decay channels in the same experiment. This measurement yields rapidity densities near midrapidity, from the two decay channels, of 2.05 +/- 0.14(stat) +/- 0.25(syst) and 2.04 +/- 0.49(stat) +/- 0.32(syst), respectively. The shape of the measured transverse momentum spectrum is also in close agreement in both decay channels. The data rule out a possible enhancement of the phi yield in the leptonic over the hadronic decay channel of a factor 1.6 or larger at the 95% C.L. This rules out the discrepancy reported in the literature between measurements of the hadronic and dimuon decay channels by two different experiments.

An automated robotic approach with redundant navigation for minimal invasive extended transsphenoidal skull base surgery.

BACKGROUND: The aim of this work was to determine the feasibility of a robotic-assisted and fully automated approach to the sphenoid sinus. An image-guided robotic system was designed to address potential human errors in performing transsphenoidal sinus surgery by combining the reproducible accuracy of a robotic system with standard computer navigation. METHODS: A six-degrees of freedom robotic assistance system and an opto-electrical navigation system were combined for image-guided assistance with redundantly controlled robotics. Newly designed endoscopic instruments for robotic surgery have been developed and are described. Telemanipulatory, as well as fully automated procedures, were tested on cadaveric heads as part of a preclinical trial. RESULTS: A fully automated sphenoidotomy as well as a telemanipulatory sphenoidectomy were performed successfully on cadaveric heads. Intraoperative performance, accuracy assessment studies, as well as possible sources of stereotactic offsets are described. The mean measured robotic reproducibility accuracy was 0.056 mm (range: 0.02 - 0.14 mm) and the mean overall navigated robotic accuracy, including all transformation and registration errors was 1.53 mm (range: 1.13 - 1.89 mm) respectively. CONCLUSION: A system for robot-guided surgery in combination with redundant navigational control was developed. It allows highly accurate maneuvers, performed either in a telemanipulation mode as master-slave system or in a fully automated fashion. A sphenoidectomy on cadaveric heads was performed in both telemanipulation and fully automated modes. The overall intraoperative accuracy was in the range of the resolution of the CT images and stereotactic offsets were caused mainly due to deflections of the endoscopic operating instrument.

[Development of an active robot system for multi-modal paranasal sinus surgery]. / Entwicklung eines aktiven Robotersystems für die multimodale Chirurgie der Nasennebenhöhlen.

BACKGROUND: Severe complications in endoscopic paranasal sinus surgery are rare, however, when they occur they are often fatal. Injuries to the optic nerve or the internal carotid artery mostly occur after penetration of the sphenoid sinus' anterior wall. METHODS: We present the robot system "A 73" with its newly designed 4-canal-microendoscope and special instruments that meets the demands of endoscopic paranasal sinus surgery. A fully automated perforation of the sphenoid sinus' anterior wall was performed in five cadaveric specimens. RESULTS: The sphenoid sinus' anterior wall could be perforated without damaging the surrounding structures in all cases. Subsequently, the approach was enlarged to the desired diameter using telemanipulation mode. The analysis of both the transformation error and intraopertive accuracy showed values in the submillimeter range. CONCLUSIONS: Using a newly developed robotic system, a fully automated perforation of the sphenoid sinus' anterior wall was performed precisely and reproducibly. This approach can be enlarged in a telemanipulation mode.

Increased safety in robotic paranasal sinus and skull base surgery with redundant navigation and automated registration.

We present an advanced version of our robotic setup for paranasal sinus surgery that was developed at the Department of Otorhinolaryngology, Head and Neck Surgery in Erlangen, Germany. The system was interconnected with a redundant navigation system for increasing intraoperative safety while performing telemanipulatory as well as fully automated maneuvers.In contrast to the previous "all in one" version, we built a modular three component setup. The basic feature of the computer navigation system is the "CAPPA ENT" station. The system references by automatically detecting a referencing frame mounted on a non-invasive upper jaw mouthpiece. Software components of both systems, navigation and robotics were combined on one user interface. Accuracy as well as clinical applicability studies were carried out. For better surveillance and increased safety, we decided to evaluate the robots reproducibility errors and overall stereotactic accuracy by means of redundant navigational control on a phantom model for paranasal sinus and skull base surgery. Multiple measurements from 14 CT-markers were taken representing different surgical approaches.A modular setup was designed and was deemed feasible in its size and weight dimensions as well as its maneuvrability for application in a routine operating room environment. The navigational feedback is integrated in real time in the robots user interface. In case of blocked visibility to the Dynamic Referencing Frame the robot powers down and activates the force torque sensor, thus softening all articulating joints. We found only adequate accuracies in pinpointing a specific CT-marker both in telemanipulatory and fully automated maneuvers. No significant offsets were observed evaluating accuracies for different surgical approaches.By using redundant navigation feedback, we were able to add another safety feature, the "loss of control" function, which shuts down any robotic action. However, no increase of the absolute accuracy was observed by adding this feature. We conclude that redundant navigational control does not make the robot more accurate, but it adds a potent safety feature to the system.

[Endonasal removal of a large recurrent craniopharyngioma using intraoperative navigation]. / Endonasale Entfernung eines ausgedehnten Kraniopharyngeomrezidivs mit Hilfe der intraoperativen Navigation.

In recent years computer-navigation systems have been commonly used in the field of otorhinolaryngology. Taking its limitations and possible failures into account, this technology is considered reasonable and helpful in routine paranasal sinus surgery, particularly in revision cases and complex approaches to the lateral skull base. We report on a patient with a large recurrent craniopharyngioma, and show that the use of intraoperative navigation might even be necessary to accomplish the desired postoperative outcome in certain cases. Future developments will demonstrate whether computer assisted surgery can extend the indications for operative procedures in complex anatomical regions.

[Complications with inflammatory diseases of the nasal sinuses]. / Komplikationen bei entzündlichen Erkrankungen der Nasennebenhöhlen.

The close localization of the paranasal sinuses both to the brain and the orbit can even today lead to severe and potentially lethal complications in patients with sinusitis. These incidents are rare, however, they should be duly diagnosed and treated since fatal outcome is described in 5-10% of cases. Current diagnosis and therapy for acute inflammatory complications and mucoceles of paranasal sinuses are presented in this article.

Semihard scattering unraveled from collective dynamics by two-pion azimuthal correlations in 158A GeV/c Pb+Au collisions.

Elliptic flow and two-particle azimuthal correlations of charged hadrons and high-p(T) pions (p(T)>1 GeV/c) have been measured close to midrapidity in 158A GeV/c Pb+Au collisions by the CERES experiment. Elliptic flow (v(2)) rises linearly with p(T) to a value of about 10% at 2 GeV/c. Beyond p(T) approximately 1.5 GeV/c, the slope decreases considerably, possibly indicating a saturation of v(2) at high p(T). Two-pion azimuthal anisotropies for p(T)>1.2 GeV/c exceed the elliptic flow values by about 60% in midcentral collisions. These nonflow contributions are attributed to nearside and back-to-back jetlike correlations, the latter exhibiting centrality dependent broadening.

Enhanced production of low-mass electron-positron pairs in 40-AGeV Pb-Au collisions at the CERN SPS.

We report on first measurements of low-mass electron-positron pairs in Pb-Au collisions at the CERN SPS beam energy of 40 AGeV. The observed pair yield integrated over the range of invariant masses 0.2e(+)e(-) annihilation with a modified rho propagator. They may be linked to chiral symmetry restoration and support the notion that the in-medium modifications of the rho are more driven by baryon density than by temperature.

Universal pion freeze-out in heavy-ion collisions.

Based on an evaluation of data on pion interferometry and on particle yields at midrapidity, we propose a universal condition for thermal freeze-out of pions in heavy-ion collisions. We show that freeze-out occurs when the mean free path of pions lambda(f) reaches a value of about 1 fm, which is much smaller than the spatial extent of the system at freeze-out. This critical mean free path is independent of the centrality of the collision and beam energy from the Alternating Gradient Synchrotron to the Relativistic Heavy Ion Collider.

[Eicosanoid metabolism in peripheral blood cells in patients with cystic fibrosis]. / Untersuchungen zum Eicosanoidstoffwechsel in peripheren Blutzellen bei Patienten mit zystischer Fibrose.

BACKGROUND: The autosomal recessive inherited cystic fibrosis is the most common genetic disorder in white patients. Disturbances in the eicosanoid metabolism seem to play an important role in the pathogenesis of the disease. The present study shows examinations on the release of prostaglandin E2 (PGE2) and peptide leukotrienes (pLT) in peripheral blood cells. PATIENTS AND METHODS: In this respect heparinised blood samples of 10 cc were obtained from 25 patients with cystic fibrosis. The peripheral blood cells were separated from the remaining blood components. PGE2 and pLT were measured by a particularly developed sensitive enzyme immunoassay with specific monoclonal antibodies. Both the basal release of the metabolites and the concentrations after stimulation with arachidonic acid (AA) were explored. The control group consisted of 25 healthy individuals. RESULTS: A distinct elevation in the basal release of pLT compared to the control group was noticed. Further stimulation with AA could only be achieved to a remarkably smaller extent. In contrast to these findings no elevation of the basal release of PGE2 and no stimulative effect of AA could be detected. In general we observed a distinct shift in the eicosanoid metabolism in favour of pLT and their proinflammatory effects. CONCLUSIONS: The increased synthesis of pLT in patients with cystic fibrosis seems to play an important role in the pathogenesis of the disease. Future studies will have to proof, if we can achieve any improvement in the clinical courses in patients with cystic fibrosis using leukotriene receptor antagonists or 5-lipoxygenase inhibitors.