Neuromagnetic speech discrimination responses are associated with reading-related skills in dyslexic and typical readers.

Poor neural speech discrimination has been connected to dyslexia, and may represent phonological processing deficits that are hypothesized to be the main cause for reading impairments. Thus far, neural speech discrimination impairments have rarely been investigated in adult dyslexics, and even less by examining sources of neuromagnetic responses. We compared neuromagnetic speech discrimination in dyslexic and typical readers with mismatch fields (MMF) and determined the associations between MMFs and reading-related skills. We expected weak and atypically lateralized MMFs in dyslexic readers, and positive associations between reading-related skills and MMF strength. MMFs were recorded to a repeating pseudoword /ta-ta/ with occasional changes in vowel identity, duration, or syllable frequency from 43 adults, 21 with confirmed dyslexia. Phonetic (vowel and duration) changes elicited left-lateralized MMFs in the auditory cortices. Contrary to our hypothesis, MMF source strengths or lateralization did not differ between groups. However, better verbal working memory was associated with stronger left-hemispheric MMFs to duration changes across groups, and better reading was associated with stronger right-hemispheric late MMFs across speech-sound changes in dyslexic readers. This suggests a link between neural speech processing and reading-related skills, in line with previous work. Furthermore, our findings suggest a right-hemispheric compensatory mechanism for language processing in dyslexia. The results obtained promote the use of MMFs in investigating reading-related brain processes.

Novel VANGL1 Gene Mutations in 144 Slovakian, Romanian and German Patients with Neural Tube Defects.

Neural tube defects (NTDs) are a group of congenital malformations of the central nervous system occurring at an average rate of 1 per 1,000 human pregnancies worldwide. Numerous genetic and environmental factors are discussed to be relevant in their etiology. In mice, mutants in >200 genes including the planar cell polarity (PCP) pathway are known to cause NTDs, and recently, heterozygous mutations in the human VANGL1 gene have been described in a small subset of patients with NTDs. We performed a VANGL1 mutation analysis in 144 unrelated individuals with NTDs from Slovakia, Romania and Germany and identified 3 heterozygous missense mutations: c.613G>A (p.Gly205Arg) with an open spina bifida (lumbosacral meningomyelocele), c.557G>A (p.Arg186His) with a closed spina bifida (tethered cord and spinal lipoma) and c.518G>A (p.Arg173His) with an unknown NTD. The c.613G>A mutation was also found in a healthy sibling. None of the mutations were described previously. Findings support that heterozygous VANGL1 mutations represent hypomorphs or conditional mutants predisposing to NTDs and occur at a frequency of approximately 2.1% of open and closed spinal NTDs. The mutations (p.Arg173His, p.Arg186His, p.Gly205Arg) modified conserved regions of the VANGL1 protein and shared similarities with previously described mutants, providing further evidence for the presence of mutational hot spots in these patients.

Exendin-4 improves the oral glucose tolerance in diabetic rats: pancreas regeneration, better function of pancreatic islets, or impaired glucose uptake?

One major obstacle for successful clinical transplantation of isolated pancreatic islets (PI) is their limited survival in vivo. The aim of this study was to analyze the functional and morphological regeneration of PI in diabetic rats by Exendin-4 (Ex4) treatment in vivo. Male Wistar rats (n = 3/group) received 20 nmol/kg Ex4 i.p. for 20 days (day 0 to day +20). Diabetes was induced with 50 mg/kg streptozotocin i.v. on day -3 or on day +5. Diabetic and normal control rats received 0.9% NaCl i.p. instead. Body weight (BW), daily blood glucose (BG) and levels, oral glucose tolerance (OGT) were tested on day -5, day +10, day +20, and on day +22, ie, 48 hours after the last Ex4 injection. Histology of the pancreata ended the study on day +24. In vivo application of Ex4 could not prevent the development of diabetes. Injection of Ex4 led to a significant decrease in postprandial BG levels to 35% for 12 hours. Surprisingly, Ex4 increased postprandial BG levels up to 20% in normal rats. Ex4-treated rats showed better OGT than untreated controls. Interestingly, 48 hours after the last Ex4 injection on day +22 OGT was completely impaired. The Ex4-treated rats lost BW much faster than the untreated controls, and showed signs of gastroparesis at autopsy. Immunohistochemistry of the pancreata documented no signs of islet regeneration. Improvement of OGT in diabetic rats after Ex4 treatment may be explained by increased insulin release from the individual PI, which was confirmed by perifusion studies with isolated PI in vitro (data not shown). Yet, Ex4 may also exert an influence on the gastrointestinal tract as it delays the uptake of glucose during gastroparesis.

[Antibody treatment in colorectal cancer--what the surgeon needs to know]. / Antikörpertherapie beim metastasierten kolorektalen Karzinom--was der Chirurg wissen sollte.

Advances in the medical treatment of colorectal cancer patients have resulted in considerable improvements through the introduction of new cytotoxic drugs. The significant progress in molecular and tumour biology has produced a great number of targeted, tumour-specific, monoclonal antibodies that are now in various stages of clinical development. Two of these antibodies, cetuximab (Erbitux) und bevacizumab (Avastin), directed against the epidermal growth factor receptor (EGFR) and the vascular epithelial growth factor (VEGF), respectively, have recently been approved for use in metastatic colorectal cancer. The combination of well-known and newly developed cytotoxic agents with monoclonal antibodies makes the medical treatment of colorectal cancer patients considerably more complex, but also provides additional therapeutic strategies for patients in advanced stages of disease.

[Surgical therapy of proximal extrahepatic bile duct tumors (Klatskin tumors)]. / Die chirurgische Therapie proximaler extrahepatischer Gallengangstumoren (Klatskin-Tumoren).

Due to their anatomical position, the tendency of early infiltrative growth and their poor prognosis without treatment, klatskin tumors are challenging concerning diagnosis and therapy. In contrast to other tumors of the gastrointestinal tract, for which exact diagnostic and stage dependent therapeutic guidelines could be formulated, clear recommendations for klatskin tumors are missing. Thus, survival rates after local resection, e. g. resection of the bile duct bifurcation alone, show high rates of R1/2 resection and early tumor recurrence. With an additional hepatic resection formally curative resections and long-term survival can be improved. Extended liver resections including the portal vein provide the highest rates of R0 resections for hilar carcinomas of the extrahepatic bile duct. Survival rates after liver transplantation for klatskin tumors are not yet convincing. Promising first results have been reported for the combination of neoadjuvant treatment and liver transplantation and might show future perspectives for the treatment of klatskin tumors.

[Obtaining of mesenchymal progenitor cells from the human umbilical cord]. / Gewinnung mesenchymaler Progenitorzellen aus der humanen Nabelschnur.

BACKGROUND: Mesenchymal progenitor cells (MPCs or mesenchymal stem cells, MSC) have the capability for differentiation into various lineages of mesenchymal tissue. MPCs are widely distributed in a variety of tissues in the adult human body and also present in the fetal environment. However, MPCs are a rare population in these tissues. In this study we evaluated the possibility that MPCs or cells with MPC-like potency are present in the umbilical cord (UC). METHODS: Term UCs were collected and stored in sterile saline solution. The UCs (10 cm) were cut into 1 cm length, the vessels were striped manually and the tissue immersed in an enzyme cocktail for 3 h at 37 degrees C. The isolated umbilical cord mesenchymal progenitor cells (UCMPCs) were pelleted by low speed centrifugation, suspended and cultured. RESULTS: (1) Umbilical cord mesenchymal progenitor cells (UMPCs) could be isolated in sufficient quantities and (2) could be cultured easily. (3) These cells demonstrated a fibroblast-like phenotype. (4) They could be expanded in culture and induced to form several different types of cells. (5) In immunochemistry these cells express mesenchymal markers (CD 13, CD 105) but not haematopoetic lineage markers (CD 14 and CD 34). CONCLUSION: Our observation suggested that MPCs are present in human umbilical cord. Instead, it should be considered a valuable resource for the isolation of potent cells for cell-based therapies, especially in general and pediatric surgery.

An alternative classification of incisional hernias enlisting morphology, body type and risk factors in the assessment of prognosis and tailoring of surgical technique.

Incisional hernias occur in 5-10% of patients who have undergone laparotomy and are associated with a high morbidity and significant socioeconomic costs. Better understanding of the anatomy and improved methods for reinforcement of the abdominal wall with alloplastic meshes have reduced the recurrence rate to 1-10% depending on the type of hernia and the technique employed. A number of surgical repair techniques and mesh types are available. However, precise criteria for incorporating patient body type, risk factors for recurrence, hernia morphology, and the available biomaterials into planning of the surgical approach (open versus laparoscopic) have yet to be established. The elaboration of such criteria would require comparative evaluation of long-term results in a sufficiently large number of patients, e.g. in multicentre trials or meta-analyses of standardised data from different centres. Current classifications have the drawback that they fail to take account of prognostically relevant risk factors for recurrence and are not self-explanatory. The authors present a classification of incisional hernias that is self-explanatory and practicable in routine clinical practice. Based on the cornerstones of morphology (M), hernia size in cm (S), and risk factors for recurrence (RF), the scheme enables easy description and documentation of the hernia, and provides evidence for the indications and limitations of the main surgical repair techniques. Since randomised studies can scarcely be conducted on incisional hernias due to the numerous morphological variables, the classification presented here may offer an alternative means for comparative data analysis.