Kooperativer Bibliotheksverbund

Berlin Brandenburg

and
and

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
Filter
  • Medicine
Type of Medium
Language
Year
  • 1
    Language: English
    In: Cancer discovery, November 2011, Vol.1(6), pp.475-6
    Description: mTOR signaling is frequently deregulated in cancer, including brain tumors. Although the signaling of mTOR complex 1 (mTORC1) has been subject to intensive investigations and mTORC1 itself has been a well-established cancer drug target for years, the role of the second complex, mTORC2, remains elusive. Tanaka et al. reveal an EGFRvIII-mTORC2-NFκB signaling cascade and demonstrate that mTORC2 mediates cisplatin resistance through NF-κB in an Akt-independent manner in glioblastoma. Uncovering the role of mTORC2 in chemotherapy resistance in glioblastoma highlights the need for further investigations of mTORC2 inhibition.
    Keywords: Brain Neoplasms -- Metabolism ; Erbb Receptors -- Metabolism ; Glioblastoma -- Metabolism ; Nf-Kappa B -- Metabolism ; Transcription Factors -- Metabolism
    ISSN: 21598274
    E-ISSN: 2159-8290
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 2
    In: Neurology, 2015, Vol.84(17), pp.1782-1787
    Description: OBJECTIVES:: To investigate whether the human sciatic nerve might have a consistent somatotopic organization according to proximal fascicle input by spinal nerves. METHODS:: Twelve patients (55.3 ± 15.5 years) with confirmed lesions of either the L5 or S1 spinal nerve root underwent magnetic resonance neurography of sciatic nerve fascicles including thigh and knee levels (T2-weighted sequence with fat saturation, repetition time/echo time 7,552/52 milliseconds, voxel size 0.27 × 0.27 × 3.0 mm). Twenty healthy subjects and 12 additional patients with an established diagnosis of peripheral polyneuropathy served as 2 separate age- and sex-matched control groups. Two blinded readers assessed patients and controls for presence of distinct lesion patterns. Spatial maps of normalized T2 signal were rendered after segmentation and coregistration of sciatic nerve voxels to detect fascicle lesion patterns. RESULTS:: A clear somatotopic distribution of nerve fascicles was observed on cross-sections along the entire course of the sciatic nerve and was distinct between patients with L5 and those with S1 lesions. Fascicles emerging from L5 were ordered in anterolateral positions within sciatic nerve cross-sections, while fascicles emerging from S1 appeared posteromedially. Visual assessment discriminated these somatotopic lesions in all cases from both healthy and polyneuropathy controls. CONCLUSION:: A distinct pattern of somatotopy was identified within the sciatic nerve according to proximal fascicle input by L5 and S1 spinal nerves. Knowledge of human nerve somatotopy may have clinically useful implications in imaging-aided diagnosis of neuropathies.
    Keywords: Repetition ; Spinal Nerves ; Sciatic Nerve ; Segmentation ; Image Processing ; N.M.R. ; Maps ; Knee ; Polyneuropathy ; Neuropathy ; Neurology & Neuropathology;
    ISSN: 0028-3878
    E-ISSN: 1526632X
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 3
    Language: English
    In: PLoS ONE, 2012, Vol.7(3), p.e33449
    Description: Hypermethylation in the promoter region of the MGMT gene encoding the DNA repair protein O 6 -methylguanine-DNA methyltransferase is among the most important prognostic factors for patients with glioblastoma and predicts response to treatment with alkylating agents like temozolomide. Hence, the MGMT status is widely determined in most clinical trials and frequently requested in routine diagnostics of glioblastoma. Since various different techniques are available for MGMT promoter methylation analysis, a generally accepted consensus as to the most suitable diagnostic method remains an unmet need. Here, we assessed methylation-specific polymerase chain reaction (MSP) as a qualitative and semi-quantitative method, pyrosequencing (PSQ) as a quantitative method, and methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) as a semi-quantitative method in a series of 35 formalin-fixed, paraffin-embedded glioblastoma tissues derived from patients treated in a prospective clinical phase II trial that tested up-front chemoradiotherapy with dose-intensified temozolomide (UKT-05). Our goal was to determine which of these three diagnostic methods provides the most accurate prediction of progression-free survival (PFS). The MGMT promoter methylation status was assessable by each method in almost all cases ( n  = 33/35 for MSP; n  = 35/35 for PSQ; n  = 34/35 for MS-MLPA). We were able to calculate significant cut-points for the continuous methylation signals at each CpG site analysed by PSQ (range, 11.5 to 44.9%) and at one CpG site assessed by MS-MLPA (3.6%) indicating that a dichotomisation of continuous methylation data as a prerequisite for comparative survival analyses is feasible. Our results show that, unlike MS-MLPA, MSP and PSQ provide a significant improvement of predicting PFS compared with established clinical prognostic factors alone (likelihood ratio tests: p 〈0.001). Conclusively, taking into consideration prognostic value, cost effectiveness and ease of use, we recommend pyrosequencing for analyses of MGMT promoter methylation in high-throughput settings and MSP for clinical routine diagnostics with low sample numbers.
    Keywords: Research Article ; Medicine ; Oncology ; Pathology
    E-ISSN: 1932-6203
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 4
    Language: English
    In: 2012, Vol.7(11), p.e49742
    Description: Patients with ulnar neuropathy of unclear etiology occasionally present with lesion extension from elbow to upper arm level on MRI. This study investigated whether MRI thereby distinguishes multifocal neuropathy from focal-compressive neuropathy at the elbow. ; This prospective study was approved by the institutional ethics committee and written informed consent was obtained from all participants. 122 patients with ulnar mononeuropathy of undetermined localization and etiology by clinical and electrophysiological examination were assessed by MRI at upper arm and elbow level using T2-weighted fat-saturated sequences at 3T. Twenty-one patients were identified with proximal ulnar nerve lesions and evaluated for findings suggestive of disseminated neuropathy (i) subclinical lesions in other nerves, (ii) unfavorable outcome after previous decompressive elbow surgery, and (iii) subsequent diagnosis of inflammatory or other disseminated neuropathy. Two groups served as controls for quantitative analysis of nerve-to-muscle signal intensity ratios: 20 subjects with typical focal ulnar neuropathy at the elbow and 20 healthy subjects. ; In the group of 21 patients with proximal ulnar nerve lesion extension, T2-w ulnar nerve signal was significantly (p〈0.001) higher at upper arm level than in both control groups. A cut-off value of 1.92 for maximum nerve-to-muscle signal intensity ratio was found to be sensitive (86%) and specific (100%) to discriminate this group. Ten patients (48%) exhibited additional T2-w lesions in the median and/or radial nerve. Another ten (48%) had previously undergone elbow surgery without satisfying outcome. Clinical follow-up was available in 15 (71%) and revealed definitive diagnoses of multifocal neuropathy of various etiologies in four patients. In another eight, diagnoses could not yet be considered definitive but were consistent with multifocal neuropathy. ; Proximal ulnar nerve T2 lesions at upper arm level are detected by MRI and indicate the presence of a non-focal disseminated neuropathy instead of a focal compressive neuropathy.
    Keywords: Research Article ; Biology ; Medicine ; Immunology ; Physiology ; Neurological Disorders ; Radiology And Medical Imaging
    E-ISSN: 1932-6203
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 5
    In: Neurology, 2016, Vol.87(18), pp.1884-1891
    Description: OBJECTIVE:: To investigate the spatial pattern of lesion dispersion in posterior interosseous neuropathy syndrome (PINS) by high-resolution magnetic resonance neurography. METHODS:: This prospective study was approved by the local ethics committee and written informed consent was obtained from all patients. In 19 patients with PINS and 20 healthy controls, a standardized magnetic resonance neurography protocol at 3-tesla was performed with coverage of the upper arm and elbow (T2-weighted fat-saturated: echo time/repetition time 52/7,020 milliseconds, in-plane resolution 0.27 × 0.27 mm). Lesion classification of the radial nerve trunk and its deep branch (which becomes the posterior interosseous nerve) was performed by visual rating and additional quantitative analysis of normalized T2 signal of radial nerve voxels. RESULTS:: Of 19 patients with PINS, only 3 (16%) had a focal neuropathy at the entry of the radial nerve deep branch into the supinator muscle at elbow/forearm level. The other 16 (84%) had proximal radial nerve lesions at the upper arm level with a predominant lesion focus 8.3 ± 4.6 cm proximal to the humeroradial joint. Most of these lesions (75%) followed a specific somatotopic pattern, involving only those fascicles that would form the posterior interosseous nerve more distally. CONCLUSIONS:: PINS is not necessarily caused by focal compression at the supinator muscle but is instead frequently a consequence of partial fascicular lesions of the radial nerve trunk at the upper arm level. Neuroimaging should be considered as a complementary diagnostic method in PINS.
    Keywords: 120 ; 181 ; Article;
    ISSN: 0028-3878
    E-ISSN: 1526632X
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 6
    In: Neurology, 2014, Vol.82(7), pp.598-606
    Description: OBJECTIVE:: We sought to determine lesion sites and spatial lesion patterns in spontaneous anterior interosseous nerve syndrome (AINS) with high-resolution magnetic resonance neurography (MRN). METHODS:: In 20 patients with AINS and 20 age- and sex-matched controls, MRN of median nerve fascicles was performed at 3T with large longitudinal anatomical coverage (upper arm/elbow/forearm): 135 contiguous axial slices (T2-weighted: echo time/repetition time 52/7,020 ms, time of acquisition: 15 minutes 48 seconds, in-plane resolution: 0.25 × 0.25 mm). Lesion classification was performed by visual inspection and by quantitative analysis of normalized T2 signal after segmentation of median nerve voxels. RESULTS:: In all patients and no controls, T2 lesions of individual fascicles were observed within upper arm median nerve trunk and strictly followed a somatotopic/internal topography: affected were those motor fascicles that will form the anterior interosseous nerve further distally while other fascicles were spared. Predominant lesion focus was at a mean distance of 14.6 ± 5.4 cm proximal to the humeroradial joint. Discriminative power of quantitative T2 signal analysis and of qualitative lesion rating was high, with 100% sensitivity and 100% specificity (p 〈 0.0001). Fascicular T2 lesion patterns were rated as multifocal (n = 17), monofocal (n = 2), or indeterminate (n = 1) by 2 independent observers with strong agreement (kappa = 0.83). CONCLUSION:: It has been difficult to prove the existence of fascicular/partial nerve lesions in spontaneous neuropathies using clinical and electrophysiologic findings. With MRN, fascicular lesions with strict somatotopic organization were observed in upper arm median nerve trunks of patients with AINS. Our data strongly support that AINS in the majority of cases is not a surgically treatable entrapment neuropathy but a multifocal mononeuropathy selectively involving, within the main trunk of the median nerve, the motor fascicles that continue distally to form the anterior interosseous nerve.
    Keywords: Data Processing ; Median Nerve ; Image Processing ; Joints ; Repetition ; Classification ; Segmentation ; Peripheral Nervous System ; N.M.R. ; Elbow ; Forearm ; Neuropathy ; Topography ; Neuroanatomy, Histology & Cytology;
    ISSN: 0028-3878
    E-ISSN: 1526632X
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 7
    Language: English
    In: Current Neurology and Neuroscience Reports, 2011, Vol.11(3), pp.305-312
    Description: Antiangiogenic treatment has recently become an integral part of modern cancer therapy targeting the vasculature of numerous aggressive malignancies including glioblastoma. There is preclinical evidence that antiangiogenic therapies promote glioma cell invasiveness. In clinical series, upon progression on antiangiogenic therapy with the vascular endothelial growth factor–directed antibody bevacizumab (BEV), glioblastoma has been reported to display a more infiltrative pattern of recurrence. This distant spread at recurrence or progression and a gliomatosis cerebri-like growth pattern is best detectable on fluid-attenuated inversion recovery MRI. The frequency of up to 20% to 30% of such a pattern in BEV-treated patients is higher than expected to occur without BEV. Older reports and common clinical knowledge estimate the frequency of diffuse or distant spread in recurrent glioblastoma at 10%. This observation stimulated two streams of research. One is to overcome this often insidious adverse effect of antiangiogenic treatment, to optimize antiangiogenic therapies and to face this major challenge, integrating antiangiogenic with anti-invasive mechanisms into one combined treatment concept. The second is questioning a specific property of antiangiogenic therapy to induce diffuse or distant spread. Here, alternative hypotheses of increased awareness and better imaging as well as invasiveness being part of the natural course of the disease have been tested. Without doubt, migration and invasiveness are major obstacles to successful glioma therapy, notably local therapies, both in the natural course of the disease and in the concept of “evasive resistance.” However, clinical analyses of case series, matched pairs analyses, and follow-up on the BRAIN trial (A Study to Evaluate Bevacizumab Alone or in Combination with Irinotecan for Treatment of Glioblastoma Multiforme), which led to accelerated approval of BEV for recurrent glioblastoma in the United States, have not supported a specific propensity of BEV to induce diffuse growth or distant spread at recurrence.
    Keywords: Evasive resistance ; Recurrence pattern ; MRI ; Bevacizumab
    ISSN: 1528-4042
    E-ISSN: 1534-6293
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 8
    In: Annals of Neurology, December 2015, Vol.78(6), pp.939-948
    Description: Objective The aim of this work was to localize and quantify alterations of nerve microstructure in diabetic polyneuropathy (DPN) by magnetic resonance (MR) neurography with large anatomical coverage. Methods Patients (N=25) with mild-to-moderate (Neuropathy-Symptom-Score [NSS]/Neuropathy Deficit Score [NDS] 3.8 plus or minus 0.3/2.6 plus or minus 0.5) and patients (n=10) with severe DPN (6.2 plus or minus 0.6/7.4 plus or minus 0.5) were compared to patients (n=15) with diabetes but no DPN and to age-/sex-matched nondiabetic controls (n=25). All subjects underwent MR neurography with large spatial coverage and high resolution from spinal nerve to ankle level: four slabs per leg, each with 35 axial slices (T2- and proton-density-weighted two dimensional turbo-spin-echo sequences; voxel size: 0.40.33.5mm super(3)) and a three-dimensional T2-weighted sequence to cover spinal nerves and plexus. Nerve segmentation was performed on a total of 280 slices per subject. Nerve lesion voxels were determined independently from operator input by statistical classification against the nondiabetic cohort. At the site with highest lesion-voxel burden, signal quantification was performed by calculating nerve proton spin density and T2 relaxation time. Results Total burden of nerve lesion voxels was significantly increased in DPN (p=0.003) with strong spatial predominance at thigh level, where average lesion voxel load was significantly higher in severe (57 plus or minus 18.4; p=0.0022) and in mild-to-moderate DPN (35 plus or minus 4.0; p〈0.001) than in controls (18 plus or minus 3.6). Signal quantification at the site of predominant lesion burden (thigh) revealed a significant increase of nerve proton spin density in severe (360 plus or minus 22.9; p=0.043) and in mild-to-moderate DPN (365 plus or minus 15.2; p=0.001) versus controls (288 plus or minus 13.4), but not of T2 relaxation time (p=0.49). Nerve proton spin density predicted severity of DPN with an odds ratio of 2.9 (95% confidence interval: 2.4-3.5; p〈0.001) per 100 proton spins. Interpretation In DPN, the predominant site of microstructural nerve alteration is at the thigh level with a strong proximal-to-distal gradient. Nerve proton spin density at the thigh level is a novel quantitative imaging biomarker of early DPN and increases with neuropathy severity. Ann Neurol 2015; 78:939-948
    Keywords: Statistics ; Protons ; Image Processing ; Biomarkers ; Diabetes Mellitus ; Leg ; Spinal Nerves ; Classification ; Segmentation ; Ankle ; N.M.R. ; Brain Slice Preparation ; Polyneuropathy ; Neuropathy ; Neurology & Neuropathology;
    ISSN: 0364-5134
    E-ISSN: 1531-8249
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 9
    Language: English
    In: International Journal of Radiation Oncology, Biology, Physics, 01 July 2010, Vol.77(3), pp.670-676
    Description: To evaluate the toxicity and efficacy of chemoradiotherapy with temozolomide (TMZ) administered in an intensified 1-week on/1-week off schedule plus indomethacin in patients with newly diagnosed glioblastoma. A total of 41 adult patients (median Karnofsky performance status, 90%; median age, 56 years) were treated with preirradiation TMZ at 150 mg/m (1 week on/1 week off), involved-field radiotherapy combined with concomitant low-dose TMZ (50 mg/m ), maintenance TMZ starting at 150 mg/m using a 1-week on/1-week off schedule, plus maintenance indomethacin (25 mg twice daily). The median follow-up interval was 21.7 months. Grade 4 hematologic toxicity was observed in 15 patients (36.6%). Treatment-related nonhematologic Grade 4-5 toxicity was reported for 2 patients (4.9%). The median progression-free survival was 7.6 months (95% confidence interval, 6.2–10.4). The 1-year survival rate was 73.2% (95% confidence interval, 56.8–84.2%). The presence of gene promoter methylation in the tumor tissue was associated with significantly superior progression-free survival. The dose-dense regimen of TMZ administered in a 1-week on/1-week off schedule resulted in acceptable nonhematologic toxicity. Compared with data from the European Organization for Research and Treatment of Cancer/National Cancer Institute of Canada trial 26981-22981/CE.3, patients with an unmethylated gene promoter appeared not to benefit from intensifying the TMZ schedule regarding the median progression-free survival and overall survival. In contrast, data are promising for patients with a methylated promoter.
    Keywords: Glioblastoma ; Indomethacin ; O6-Methylguanine-DNA Methyltransferase ; Mgmt ; Radiotherapy ; Temozolomide ; Medicine
    ISSN: 0360-3016
    E-ISSN: 1879-355X
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 10
    Language: English
    In: Critical care (London, England), 2011, Vol.15(1), pp.R8
    Description: To accomplish early enteral feeding in the critically ill patient a new transnasal endoscopic approach to the placement of postpyloric feeding tubes by intensive care physicians was evaluated. This was a prospective cohort study in 27 critically ill patients subjected to transnasal endoscopy and intubation of the pylorus. Attending intensive care physicians were trained in the handling of the new endoscope for transnasal gastroenteroscopy for two days. A jejunal feeding tube was advanced via the instrument channel and the correct position assessed by contrast radiography. The primary outcome measure was successful postpyloric placement of the tube. Secondary outcome measures were time needed for the placement, complications such as bleeding and formation of loops, and the score of the placement difficulty graded from 1 (easy) to 4 (difficult). Data are given as mean values and standard deviation. Out of 34 attempted jejunal tube placements, 28 tubes (82%) were placed correctly in the jejunum. The duration of the procedure was 28 ± 12 minutes. The difficulty of the tube placement was judged as follows: grade 1: 17 patients, grade 2: 8 patients, grade 3: 7 patients, grade 4: 2 patients. In three cases, the tube position was incorrect, and in another three cases, the procedure had to be aborted. In one patient bleeding occurred that required no further treatment. Fast and reliable transnasal insertion of postpyloric feeding tubes can be accomplished by trained intensive care physicians at the bedside using the presented procedure. This new technique may facilitate early initiation of enteral feeding in intensive care patients.
    Keywords: Critical Care ; Point-of-Care Systems -- Methods ; Enteral Nutrition -- Instrumentation ; Intubation, Gastrointestinal -- Methods ; Medical Staff, Hospital -- Education
    E-ISSN: 1466-609X
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. Further information can be found on the KOBV privacy pages