Design of a Peptide-Based Electronegative Hydrogel for the Direct Encapsulation, 3D Culturing, in Vivo Syringe-Based Delivery, and Long-Term Tissue Engraftment of Cells.

Soft materials that facilitate the three-dimensional (3D) encapsulation, proliferation, and facile local delivery of cells to targeted tissues will aid cell-based therapies, especially those that depend on the local engraftment of implanted cells. Herein, we develop a negatively charged fibrillar hydrogel based on the de novo-designed self-assembling peptide AcVES3-RGDV. Cells are easily encapsulated during the triggered self-assembly of the peptide leading to gel formation. Self-assembly is induced by adjusting the ionic strength and/or temperature of the solution, while avoiding large changes in pH. The AcVES3-RGDV gel allows cell-material attachment enabling both two-dimensional and 3D cell culture of adherent cells. Gel-cell constructs display shear-thin/recovery rheological properties enabling their syringe-based delivery. In vivo cellular fluorescence as well as tissue resection experiments show that the gel supports the long-term engraftment of cells delivered subcutaneously into mice.

[Surgical treatment of acute mediastinitis]. / Therapie der akuten Mediastinitis.

Despite modern intensive care management, acute mediastinitis is still associated with a high morbidity and mortality (up to approximately 40 %). Effective antibiotic therapy, intensive care management, elimination of the causative sources of infection and drainage of the affected mediastinal compartments are the cornerstones of therapy in a multidisciplinary treatment concept. Early diagnosis, prompt and uncompromising initial therapy and planned computed tomography (CT) control after the first stages of therapy in order to decide on the necessity for surgical re-interventions are essential for achieving optimal results. Knowledge of the specific anatomical characteristics is crucial for the understanding of this disease and its treatment; therefore, the current knowledge on fascial layers and interstitial spaces from the neck to the mediastinum is described and discussed. A possible foudroyant spread of the infection, especially within the posterior mediastinum, has to be anticipated. The approach to the mediastinum depends on the mediastinal compartments affected, on the causative disease and on the patient's clinical situation. The surgical approach should be adapted to the particular clinical situation of the individual patient and to the surgical experience of the surgeon. When in doubt, the more invasive approach to the mediastinum, such as bilateral thoracotomy, is recommended. An ascending mediastinitis due to pancreatitis is a very rare condition; however, as chest pains are often the main clinical sign surgeons should be aware of this differential diagnosis. An intraoperative brown-black serous fluid in the mediastinal tissue is virtually pathognomonic. The treatment results of esophageal perforation as the most frequent cause of mediastinitis have been improved by integration of various interventional procedures. Hyperbaric oxygen therapy or immunoglobulin treatment can play an auxiliary role in selected patients with acute mediastinitis.

[Physiology of the upper esophageal sphincter]. / Physiologie des oberen Ösophagussphinkters.

The upper esophageal sphincter (UES) forms a barrier between the pharynx and the esophagus. When opened, the UES allows the food bolus to pass into the esophagus, as well as permitting emesis and eructation. The basal sphincter tone constitutes a barrier function which serves to prevent reflux and passive aerophagia in the case of deep breathing. Basal sphincter tone is dependent on several influencing factors; during swallowing, sphincter opening and closure follow a complex multiphase pattern. This article presents an overview of the current understanding of UES physiology.

[Anatomy of the upper esophageal sphincter]. / Anatomie des oberen Ösophagussphinkters.

The upper esophageal sphincter (UES) forms a barrier between the pharynx and the esophagus. When closed, the barrier function serves to prevent reflux and aerophagia; when open, swallowing, belching and vomiting are possible. The closing muscles include caudal parts of the inferior pharyngeal sphincter and cranial parts of the upper esophagus musculature. Sphincter opening is achieved by muscles that insert from the outside to connect to the larynx and pharynx in the sphincter region. The closing muscles are innervated by branches of the glossopharyngeal and vagal nerves, and central control is probably mediated by several reflexes. This article presents an overview of the current understanding of the complex UES anatomy.

[Cerebral lesions in acute arterial hypertension: the characteristic MRI in hypertensive encephalopathy]. / Zerebrale Veränderungen bei krisenhafter arterieller Hypertonie: MRT-Befunde der hypertensiven Enzephalopathie sind wegweisend für Diagnose und Therapie.

PURPOSE: In the nine years since the posterior reversible (leuc) encephalopathy syndrome (PRES) was first described, a number of causes have been under discussion. These not only include arterial hypertension, i. e. hypertensive crises, but also various toxic substances, i. e. immunosuppressive or chemotherapeutic agents, that are responsible for the formation of the symptoms and characteristic MR tomographic brain findings. MATERIALS AND METHODS: Initial and follow-up MRI examinations of 8 patients were analyzed. All patients had acute neurological symptoms (headaches, seizures, visual disorders and vigilance disturbances) together with a detectable hypertensive crisis. RESULTS: MRI disclosed increased signal intensity in subcortical and some cortical lesions in all patient FLAIR sequences. These changes were particularly extensive in the posterior circulation (occipital, cerebellum and brain stem) although they were also detected in brain areas supplied by the carotid artery. However, a cytotoxic genesis of the changes was ruled out in each patient by means of a normal DWI. Furthermore, when the blood pressure was normalized, reversibility of the lesions as proof of the diagnosis was detectable. CONCLUSION: The imaging findings can be typically analyzed as a predominantly posterior distribution of encephalopathic lesions with a high probability of reversibility after lowering blood pressure was patients suffering from a critical increase in blood pressure with corresponding neurological symptoms. The exact pathophysiology remains unclear, but the cause currently most favored is a vasculopathy of the posterior circulation due to diminished adrenergic autoregulation in combination with a dysfunction of the endothelial cells. In conclusion, we suggest designating this subpopulation from the non-uniform pool of patients with posterior (leuc) encephalopathy as "hypertensive encephalopathy". "Hypertensive encephalopathy" has to be distinguished from "toxic encephalopathy", particularly due to different therapeutic and prognostic consequences.

Profound midbrain atrophy in patients with Wilson's disease and neurological symptoms?

Wilson's disease (WD) is characterized by impaired hepatic copper secretion and subsequent copper accumulation in many organs predominantly liver and brain, secondary to loss of function mutations in the copper transport protein ATP7B. If the disease is recognized too late or treatment is not adequate, brain copper accumulation leads to progressive neurodegeneration with a variety of clinical symptoms. The nigrostriatal dopaminergic system seems rather vulnerable. Midbrain atrophy, however, has not been recognized as one of the prime features of patients with WD. Here we report quantification of midbrain diameter in 41 patients with WD. Data were correlated to the severity of neurological symptoms and the integrity of dopaminergic neurons measured via dopamine transporter binding. For control, we measured midbrain diameter in 18 patients with no evidence for brainstem dysfunction and 5 patients with progressive supranuclear palsy (PSP). Patients with WD had a reduced midbrain diameter (15.5 +/- 0.4 mm) compared to controls (18.5 +/- 0.2 mm). WD patients without neurological symptoms had midbrain diameter that were not different from controls (18.0 +/- 0.3 mm), while patients with neurological symptoms showed midbrain atrophy similar to patients with PSP (14.4 +/- 0.3 mm versus 14.1 +/- 0.3). There was a strong and significant correlation between midbrain atrophy and the severity of neurological symptoms (r= -0.68, p < 0.001) while midbrain atrophy and dopamine transporter binding correlated significantly but was less pronounced (r=0.46, p < 0.001). In summary, we were able to show, that midbrain diameter is an easy to perform quantification of neurodegeneration induced by brain copper accumulation and that other structures than substantia nigra dopaminergic neurons seem to contribute to midbrain atrophy in WD.

[Correlation of clinical aspects as well as genotype and phenotype in Wilson's disease on the basis of epidemiologic, clinical and cranial MRI findings]. / Klinische und Genotyp-Phänotyp-Korrelation epidemiologischer, bildgebender und neurologischer Befunde bei Patienten mit Morbus Wilson.

Wilson's disease, a rare autosomal recessive disorder of hepatic copper transport, is characterized by a varying pattern of hepatic, neurologic and psychiatric symptoms. Currently, about 250 causative mutations of the ATP 7B gene are known. However, a correlation between genotype and phenotype according to these mutations is not yet clear. To elucidate a possible correlation in this study 39 patients with Wilson's disease were subdivided into three groups according to the underlying mutation in group I for homocygote respectively group II for compound heterocygote mutation in H1069Q and group III for other mutations. Clinical subtype and extent of neurologic disturbance as well as epidemiologic aspects, presence of psychiatric symptoms, results of acustically evoked potentials (Wave III, interpeak latency III-V) and findings of cranial MRI were considered. While psychopathological symptoms, the results of acustically evoked potentials and cranial MRI show a correlation to the clinical subtype of Wilson's disease there was no genotype-phenotype correlation on the basis of the mutation in H1069Q. The qualitative and quantitative pattern of results do not show any significant differences in the three groups of genotype. Thus, the time of treatment onset still has most influence on the extent of clinical manifestation and reversibility of the toxic copper accumulation.

Evaluation of intra-operative ultrasound imaging in brain tumor resection: a prospective study.

AIMS: The purpose of our study was to evaluate intra-operative ultrasound (IOUS) as a tool of resection control after brain tumor surgery. In addition, we looked for tumor species suitable for ultrasound representation. METHODS: Using a Siemens Omnia Sonoline Ultrasound, 36 tumors were examined, high-grade gliomas (62%), metastases (22%) and others (16%). We focused on tumor imaging by ultrasound with regard to its reliability of tumor expansion and margins. Evaluation of the images was carried out by correlating the ultrasound-based intra-operative measured tumor volume before and after resection with a pre- and post-operative (within 48 hours) measured volume by MRI. The IOUS measurements were performed by the neurosurgeon and the MRI measurements by the neuroradiologist. Thus, the measurement procedures were blinded. Corresponding to a deviation of the ultrasound volume by 10, 20 and > 20% from the MRI volume, the correlation was ranked good, moderate and poor. For assessing the agreement between these two methods of imaging, the statistical analysis was conducted using a method described by Bland and Altman. RESULTS: High-grade gliomas mostly showed a moderate or poor correlation in comparing IOUS- and MRI-tumor volumetry resulting in incomplete resection. Metastases resulted in a good to moderate correlation with a satisfactory extent of resection. The other tumors had poor images with larger tumor residues. The MRI measured volumes tended to be larger on average; the deviation grew with tumor size . CONCLUSION: The reliability of IOUS depends on tumor type. It is beneficial to use IOUS for the resection of metastases and a few high-grade gliomas. Concerning the volumetric accuracy, the value of IOUS is worse than its value of navigation and resection control.

Movement of the upper cervical spine during laryngoscopy: a comparison of the Bonfils intubation fibrescope and the Macintosh laryngoscope.

The movements of the upper cervical spine were measured by fluoroscopy in 20 patients during laryngoscopy with the Bonfils intubation fibrescope and the Macintosh laryngoscope. Laryngoscopy with both the Bonfils intubation fibrescope and the Macintosh laryngoscope resulted in significant extension of the cervical spine as compared to the neutral position but this extension was significantly less with the Bonfils intubation fibrescope than with the Macintosh (p = 0.001). However, the atlanto-occipital distance was significantly greater during laryngoscopy with the Bonfils intubation fibrescope (p = 0.002), and the angle between the occiput and C1 differed significantly between the two techniques (p = 0.001). With the Bonfils intubation fibrescope, significantly less extension was also found at the C1/C2 and C3/C4 levels (p = 0.001 and p = 0.049, respectively). There is therefore significantly less movement of the upper cervical spine during laryngoscopy with the Bonfils fibrescope compared with the Macintosh laryngoscope.

[Tumour necrosis factor receptor-associated periodic syndrome. A rare differential diagnosis of multiple sclerosis]. / TNF-Rezeptor-assoziiertes periodisches Syndrom. Seltene Differenzialdiagnose der Multiplen Sklerose.

Tumour necrosis factor receptor-associated periodic syndrome (TRAPS), a rare autosomal dominant disorder, is characterised by recurrent attacks of fever, myalgias, and abdominal pain. However, manifestations in the central nervous system are hardly known. We describe a family in which one of three affected members developed central nervous system symptoms. First diagnosed as multiple sclerosis (MS), the demyelinisation seems to be a feature of TRAPS rather than MS. The syndrome is discussed as a rare differential diagnosis of MS.

Pediatric MR-guided interventions.

MRI guided interventions are a relatively new but steadily growing field within surgery in pediatric age. Besides the advantages of MRI, such as multiplanar capability and excellent soft tissue contrast and spatial resolution, particularly relevant for the pediatric population is the lack of ionizing radiation. There is meanwhile a group of well defined diagnostic or therapeutic indications for applying MR imaging during pediatric interventions. Aim of this review is to give an overview about indications of MR-guided procedures in children as well as the advantages and disadvantages of MR-guided interventions. We also briefly discuss interventional MR-systems and MR-compatible devices. It is our opinion that MR-guidance for pediatric interventions is a promising technique at the beginning of its development.

Fatal bihemispheric intracerebral hemorrhage after burrhole evacuation of chronic subdural hematoma in a bone marrow-transplanted patient: case report and review of the literature.

BACKGROUND: Intracranial hemorrhage seems to be a relatively frequent complication following bone marrow transplantation (BMT). The neurosurgical management of these patients can be problematic. CASE DESCRIPTION: We report about a 46-year-old patient, who had BMT because of a Pre-T-ALL and who developed symptomatic bihemispheric chronic subdural hematomas (cSDHs). Pre-T-ALL is a form of an acute lymphatic leukemia of T cell type characterized by certain immunologic markers with a worse prognosis. A few hours after evacuation of the cSDHs, the patient developed a fulminant intracerebral hemorrhage on each hemisphere and expired 2 days later. We reviewed the literature reporting similar cases to discuss the indication for a neurosurgical intervention. CONCLUSION: We presume a higher incidence of intracranial hemorrhage in BMT patients than reported. This is caused by the pathologically altered parenchyma related to the extensive therapy in these patients. BMT patients are typically at high risk for intracranial bleeding and are treated conservatively or surgically. We cannot generally recommend the conservative management for symptomatic subdural hematomas/hygromas. The risk for an acute worsening, secondary to repeated hemorrhage, is equivalent to the risk of surgical intervention. Although the outcome of our case is tragic, it should not deter surgical intervention.

[First clinical experience with extended planning and navigation in an interventional MRI unit]. / Erste klinische Erfahrungen mit einer erweiterten Eingriffsplanung und Navigation am interventionellen MRT.

PURPOSE: To present an advanced concept for patient-based navigation and to report on our first clinical experience with interventions in the cranium, of soft-tissue structures (breast, liver) and in the musculoskeletal system. MATERIALS AND METHODS: A PC-based navigation system was integrated into an existing interventional MRI environment. Intraoperatively acquired 3D data were used for interventional planning. The information content of these reference data was increased by integration of additional image modalities (e. g., fMRI, CT) and by color display of areas with early contrast media enhancement. Within 18 months, the system was used in 123 patients undergoing interventions in different anatomic regions (brain: 64, paranasal sinus: 9, breast: 20, liver: 17, bone: 9, muscle: 4). The mean duration of 64 brain interventions was compared with that of 36 procedures using the scanner's standard navigation. RESULTS: In contrast with the continuous scanning mode of the MR system (0.25 fps), the higher quality as well as the real time display (4 fps) of the MR images reconstructed from the 3D reference data allowed adequate hand-eye coordination. With our system, patient movement and tissue shifts could be immediately detected intraoperatively, and, in contrast to the standard procedure, navigation safely resumed after updating the reference data. The navigation system was characterized by good stability, efficient system integration and easy usability. Despite additional working steps still to be optimized, the duration of the image-guided brain tumor resections was not significantly longer. CONCLUSION: The presented system combines the advantage of intraoperative MRI with established visualization, planning, and real time capabilities of neuronavigation and can be efficiently applied in a broad range of non-neurosurgical interventions.

Laser-induced thermotherapy of neoplastic lesions in the brain--underlying tissue alterations, MRI-monitoring and clinical applicability.

Laser-induced thermotherapy (LITT) is a minimally invasive neurosurgical approach to the stereotactic treatment of brain tumors in poorly accessible regions. Its clinical applicability has been shown in several experimental and clinical studies under on-line monitoring by magnetic resonance imaging (MRI). This review characterizes LITT as an alternative neurosurgical approach with specific focus on the typical histological alterations and ultrastructural cellular changes following laser irradiation in the central nervous system. The spatial and temporal pattern of these changes is discussed in their relevance to the neurosurgical treatment of neoplastic lesions using LITT.