Abundance of Flt3 and its ligand in astrocytic tumors.

BACKGROUND: Molecular targeted therapies for astrocytic tumors are the subject of growing research interest, due to the limited response of these tumors, especially glioblastoma multiforme, to conventional chemotherapeutic regimens. Several of these approaches exploit the inhibition of receptor tyrosine kinases. To date, it has not been elucidated if fms-like tyrosine kinase-3 (Flt3) and its natural ligand (Flt3L) are expressed in astrocytic tumors, although some of the clinically intended small-molecule receptor tyrosine kinase inhibitors affect Flt3, while others do not. More importantly, the recent proof of principle for successful stimulation of the immune system against gliomas in preclinical models via local Flt3L application requires elucidation of this receptor tyrosine kinase pathway in these tumors in more detail. This therapy is based on recruitment of Flt3-positive dendritic cells, but may be corroborated by activity of this signaling pathway in glioma cells. METHODS: Receptor and ligand expression was analyzed by real-time polymerase chain reaction in 31 astrocytic tumors (six diffuse and 11 anaplastic astrocytomas, 14 glioblastomas) derived from patients of both genders and in glioblastoma cell lines. The two most common activating mutations of the Flt3 gene, ie, internal tandem duplication and D835 point mutation, were assessed by specific polymerase chain reaction. RESULTS: A relatively high abundance of Flt3L mRNA (4%-6% of the reference, b2 microglobulin) could be demonstrated in all tumor samples. Flt3 expression could generally be demonstrated by 40 specific polymerase chain reaction cycles and gel electrophoresis in 87% of the tumors, including all grades, although the small quantities of the receptor did not allow reliable quantification. Expression of both mRNAs was verified in the cell lines, excluding a derivation solely from contaminating lymphocytes or macrophages. No activating mutations were found. CONCLUSION: Our results warrant further analysis of endogenous Flt3 signaling in these tumors prior to application of immunotherapy in human patients.

Lumbar arachnoiditis and thecaloscopy: brief review and proposed treatment algorithm.

The term arachnoiditis describes the inflammation of the meninges and subarachnoid spaces. Lumbar arachnoiditis is characterized by obliterated nerve root sleeves and the adherence of nerve roots to each other in the proximity of the cauda equina, and may be secondary to infectious diseases or tumors, iatrogenic (subsequent to spinal surgery) or idiopathic. It is not very clearly defined epidemiologically or clinically, and various theories regarding its pathophysiology have been proposed; furthermore, its treatment is difficult because there is a lack of evidence-based diagnostic and therapeutic gold standards. Thecaloscopy has been recently described as a novel technique for retrograde transcutaneous neuroendoscopic inspection of the subarachnoid structures of the lumbar thecal sac; it has also been suggested for the treatment of lumbar arachnoiditis. We here review the most modern techniques for the treatment of this disease such as thecaloscopy and neurostimulation.

The PFKFB3 splice variant UBI2K4 is downregulated in high-grade astrocytomas and impedes the growth of U87 glioblastoma cells.

AIMS: Fructose-2,6-bisphosphate, a key regulator of glycolysis, is synthesized and degraded by four different isozymes of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFKFB1-4). The PFKFB3 isozyme is upregulated in several human tumours. Six alternatively spliced variants of PFKFB3 mRNA are known in humans (UBI2K1-6). Here, we studied the role of the PFKFB3 splice variants in human astrocytic gliomas. METHODS: We analysed the PFKFB3 splice variants in 48 astrocytic gliomas by RT-PCR and real-time PCR. The effect of transient and stable overexpression of the PFKFB3 isoforms was studied in U87 glioblastoma cells by MTT, cell counting, clone formation assay and metabolic measurements. RESULTS: UBI2K5 and UBI2K6 are the predominant splice variants in rapidly proliferating high-grade astrocytomas while the expression of UBI2K3 and UBI2K4 is mainly restricted to low-grade astrocytomas and nonneoplastic brain tissue. Overexpression of UBI2K5 or UBI2K6 in the U87 glioblastoma cell line enhances the glycolytic flux but does not affect cell growth. In contrast, overexpression of UBI2K4 reduces cell viability and anchorage-independent growth of U87 cells. The UBI2K4 mRNA level is downregulated in astrocytic gliomas with increasing malignancy grade. Moreover, the UBI2K4 mRNA level correlates with growth rate of several human cancer cell lines derived from different tissue types. CONCLUSIONS: Our results demonstrate that the splice variant UBI2K4 impedes the tumour cell growth and might serve as a tumour suppressor in astrocytic tumours.

Sectioning of filum terminale externum using a rigid endoscope through the sacral hiatus. Cadaver study.

AIM: Tethered cord syndrome (TCS) is a stretch-induced functional disorder of the spinal cord, which is directly related to filum fixation. Classic surgical approaches to the filum involve open surgery and include varying amounts of spinal bone removal. In an effort to reduce the morbidity and mortality of these procedures, the authors explored a less invasive method. They evaluated the ability, safety and feasibility for endoscopic sectioning of the filum terminale externum by performing upward orientated navigation in the extradural sacral spinal canal through the sacral hiatus using a rigid endoscope. METHODS: Four adult, phenol-formalin embalmed cadavers were used for endoscopic section of the filum terminale externum at the tip of thecal sac. After preparing the anatomical area of sacral hiatus, a rigid endoscope (Storz, of 3.8 mm external diameter with two working channels, of 1 mm each, one for suction-irrigation and one as working) was inserted into the extradural sacral spinal canal and the filum terminale externum was identified and cut easily at the distal end of thecal sac at the level of S2. In all cases, it was possible to manipulate the rigid endoscope and inspect the full length of the extradural sacral spinal canal, especially at the S1-S2 level. RESULTS: The results indicate that the tested transhiatal approach for upward orientated extradural endoscopy represents a minimally invasive procedure that provides an appropriate and feasible route to the extradural sacral spinal canal. CONCLUSION: Such approach is an attractive alternative for filum terminale externum sectioning in cases where tethered cord syndrome is not accompanied by any other pathology. Moreover if filum terminale internum sectiong is indicated, it can be performed in second stage.

[Adhesive lumbar arachnoiditis. Endoscopic subarachnoepidurostomy as a new treatment]. / Lumbale adhäsive Arachnoiditis. Endoskopische Subarachnoepidurostomie als neue Behandlungsmöglichkeit.

BACKGROUND: Adhesive lumbar arachnoiditis is essentially an unknown, unreported, and unrecognised disease. It was better known at a time when oil-based dye was used for myelography. The factors causing this pathogenesis remain unknown. In addition, diagnosis is hard to achieve and frequently attained only by an exclusion process. Only in severe cases, using high-resolution MRI, is evidence for the diagnosis obtainable. METHOD/PATIENTS: Modern neuroendoscopic techniques allow diagnosis at a reasonable risk (comparable with lumbar tap) and enable us substantially to treat the pain. Taken together, this means a radical new method of treatment for adhesive arachnoiditis. The treatment of a 23-patient research group suffering from adhesive lumbar arachnoiditis is monitored and described. RESULTS: Various endoscopic manoeuvres were carried out. Endoscopic reduction of adhesions and internal shunting for CSF flow between subarachnoidal and epidural space improved both the biomechanical abilities of rootlets and restoration of blocked CSF pathways. Its main result is the significant reduction of long-term pain registered by a visual analogue pain scale. No bad side effect other than temporary headache was found. No CSF leak syndrome was observed. DISCUSSION: The success of the method was directly influenced by the interventional procedure on the disturbed CSF circulation and its partial restoration (subarachnoepidurostomy). In cases of severe lumbar adhesive arachnoiditis, it was found very beneficial to implant special gravity-controlled valve systems for subarachnoid-peritoneal shunts. CONCLUSION: Adhesive lumbar arachnoiditis is no longer a devastating diagnosis. Due to a novel endoscopic treatment of the local CSF disturbances that restores physiologic pathways, the chance exists for long-lasting improvement of the clinical condition.

Thecaloscopy part III: first clinical application.

PURPOSE: We have already dealt with the technical and anatomical basics for thecaloscopy. The first results of clinical application are presented and the indications for its diagnostic and therapeutic use are described. The aetiology of aseptic arachnitis and the term "Wide spinal canal syndrome" are discussed. PATIENTS AND METHODS: Twelve patients who fulfilled the criteria for entry to the study were selected and the criteria were chosen according to German medical and legal rules. All patients underwent an endoscopic inspection and, if necessary, therapeutic manipulation under general anaesthesia. RESULTS: In all cases the procedure was safely and successfully performed. The pathomorphology of the arachnoid was detected and endoscopically treated in almost all cases. Arachnoid cysts were successfully fenestrated and an intraspinal meningocoele treated with endoscopic assistance. CONCLUSION: Thecaloscopy is a safe procedure if skilfully performed. It provides an opening for a wide range of new diagnostic and therapeutic options.

Directed control of electroosmotic flow in nonaqueous electrolytes using poly(ethylene glycol) coated capillaries.

Poly(ethylene glycol) (PEG)-coated capillaries exhibit unique properties in nonaqueous electrolytes. Immobilized PEG interacts significantly with different cations present in nonaqueous electrolytes. This can induce a positive surface charge on PEG-coated capillaries and results in an adjustable anodic electroosmotic flow (EOF) in nonaqueous electrolytes whereas a reduced cathodic EOF is observed in aqueous electrolytes. The EOF can reversibly be adjusted by the variation of the electrolyte constitution, namely the type of the solvent used and the nature and concentration of background cations. In methanol and especially in acetonitrile electrolytes the magnitude and also the direction of EOF is strongly dependent on the water content. Using different alkali metal cations, the EOF can be increased, reduced, or even reversed depending on the nature of the cation. The directed manipulation of EOF in methanolic electrolytes using PEG-coated capillaries was applied for optimization of nonaqueous capillary electrophoretic separations of acidic compounds with regard to reproducibility, resolution, and analysis time.

[Erroneous laterality marking in CT of the head. A case report]. / Fehlerhafte Seitenbezeichnung im Kopf-CT. Fallbericht.

Erroneous left/right side marker during CT-scanning of the head is an extremely rare event. We report a case occurred in emergency situation and present a simple device to avoid such an error.