A multi-institutional initiative on patient-related quality assurance: Independent computational dose verification of fluence-modulated treatment techniques.

PURPOSE: This multi-institutional study investigates whether computational verification of fluence-modulated treatment plans using independent software with its own Strahlerkopfmodel is an appropriate method for patient-related quality assurance (PRQA) in the context of various combinations of linear accelerators (linacs), treatment techniques and treatment planning systems (TPS). MATERIALS AND METHODS: The PRQA-software's (Mobius3D) recalculations of 9 institutions' treatment plans were analyzed for a horseshoe-shaped planning target volume (PTV) inside a phantom. The recomputed dose distributions were compared to a) the dose distributions as calculated by all TPS's and b) the measured dose distributions, which were acquired using the same independent measuring system for all institutions. Furthermore, dose volume histograms were examined. The penumbra deviations and mean gamma values were quantified using Verisoft (PTW). Additionally, workflow requirements for computational verification were discussed. RESULTS: Mobius3D is compatible with all examined TPSs, treatment techniques and linacs. The mean PTV dose differences (Mobius3D-TPS, <3.0%) and 3D gamma passing rates (>95.0%) led to a positive plan acceptance result in all cases. These results are similar to the outcome of the dosimetric measurements with one exception. The mean gamma values (<0.5) show a good agreement between Mobius3D and the TPS dose distributions. CONCLUSION: Using Mobius3D was proven to be an appropriate computational PRQA method for the tested combinations of linacs, treatment techniques and TPS's. The clinical use of Mobius3D has to be complemented with regular dosimetric measurements and thorough linac and TPS QA. Mobius3D's computational verification reduced measurement effort and personnel needs in comparison to dosimetric verifications.

Magnetic Resonance Imaging Artifacts and Cochlear Implant Positioning at 1.5 T In Vivo.

OBJECTIVE: Cerebral magnetic resonance imaging with the magnet of the cochlear implant receiver/stimulator in place causes artifacts and hinders evaluation of intracerebral structures. The aim of this study was to evaluate the internal auditory canal and the labyrinth in a 1.5T MRI with the magnet in place. STUDY DESIGN: Observational study. SETTING: Tertiary referral center. SUBJECTS AND METHODS: The receiver/stimulator unit was placed and fixed onto the head of three volunteers at three different angles to the nasion-outer ear canal (90°-160°) and at three different distances from the outer ear canal (5-9 cm). T1 and T2 weighted sequences were conducted for each position. RESULTS: Excellent visibility of the internal auditory canal and the labyrinth was seen in the T2 weighted sequences with 9 cm between the magnet and the outer ear canal at every nasion-outer ear canal angle. T1 sequences showed poorer visibility of the internal auditory canal and the labyrinth. CONCLUSION: Aftercare and visibility of intracerebral structures after cochlear implantation is becoming more important as cochlear implant indications are widened worldwide. With a distance of at least 9 cm from the outer ear canal the artifact induced by the magnet allows evaluation of the labyrinth and the internal auditory canal.

Patient-related quality assurance with different combinations of treatment planning systems, techniques, and machines : A multi-institutional survey.

PURPOSE: This project compares the different patient-related quality assurance systems for intensity-modulated radiation therapy (IMRT) and volumetric-modulated arc therapy (VMAT) techniques currently used in the central Germany area with an independent measuring system. MATERIALS AND METHODS: The participating institutions generated 21 treatment plans with different combinations of treatment planning systems (TPS) and linear accelerators (LINAC) for the QUASIMODO (Quality ASsurance of Intensity MODulated radiation Oncology) patient model. The plans were exposed to the ArcCHECK measuring system (Sun Nuclear Corporation, Melbourne, FL, USA). The dose distributions were analyzed using the corresponding software and a point dose measured at the isocenter with an ionization chamber. RESULTS: According to the generally used criteria of a 10 % threshold, 3 % difference, and 3 mm distance, the majority of plans investigated showed a gamma index exceeding 95 %. Only one plan did not fulfill the criteria and three of the plans did not comply with the commonly accepted tolerance level of ±3 % in point dose measurement. CONCLUSION: Using only one of the two examined methods for patient-related quality assurance is not sufficiently significant in all cases.

Pathological impact of hepatitis B virus surface proteins on the liver is associated with the host genetic background.

BACKGROUND: While the immune pathogenesis caused by hepatitis B virus (HBV) infection has been studied extensively, little is known about direct pathogenic effects of HBV surface proteins. Here, we have investigated pathological cellular effects of HBV surface protein expression in the liver of transgenic mice with different genetic background. METHODS: The impact of HBV surface protein expression on the liver was studied in two mouse strains, BALB/c and C57BL/6. Histology and hydroxyproline assays were performed to investigate liver morphology and fibrosis. Gene expression and signaling were analyzed by microarray, qPCR and Western blotting. RESULTS: Expression of HBV surface proteins in the liver of transgenic mice induced activation of protein kinase-like endoplasmic reticulum kinase (PERK) and eukaryotic initiation factor 2α (eIF2α) phosphorylation. Phosphorylation of eIF2α resulted in activation of the ER stress markers glucose regulated protein (GRP) 78 and pro-apoptotic C/EBP homologous protein (CHOP) in transgenic mice on BALB/c genetic background leading to stronger liver injury and fibrosis in comparison with transgenic mice on C57BL/6 background. Hepatic stellate cells represented the main collagen-producing liver cells in HBV transgenic mice. The key regulators of hepatocyte proliferation, transcription factors c-Jun and STAT3 were activated in HBV transgenic mice. Tumour incidence in transgenic mice was strain- and sex-dependent. CONCLUSIONS: Extent of liver injury, fibrosis, and tumour development induced by hepatic HBV surface protein expression considerably depends on host genetic background.

Visfatin/pre-B-cell colony-enhancing factor (PBEF), a proinflammatory and cell motility-changing factor in rheumatoid arthritis.

Adipokines such as adiponectin and visfatin/pre-B-cell colony-enhancing factor (PBEF) have been recently shown to contribute to synovial inflammation in rheumatoid arthritis (RA). In this study, we evaluated the pathophysiological implication of visfatin/PBEF in the molecular patterns of RA synovial tissue, focusing on RA synovial fibroblasts (RASFs), key players in RA synovium. Expression of visfatin/PBEF in synovial fluid and tissue of RA patients was detected by immunoassays and immunohistochemistry. RASFs were stimulated with different concentrations of visfatin/PBEF over varying time intervals, and changes in gene expression were evaluated at the RNA and protein levels using Affymetrix array, real-time PCR, and immunoassays. The signaling pathways involved were identified. The influence of visfatin/PBEF on fibroblast motility and migration was analyzed. In RA synovium, visfatin/PBEF was predominantly expressed in the lining layer, lymphoid aggregates, and interstitial vessels. In RASFs, visfatin/PBEF induced high amounts of chemokines such as IL-8 and MCP-1, proinflammatory cytokines such as IL-6, and matrix metalloproteinases such as MMP-3. Phosphorylation of p38 MAPK was observed after visfatin/PBEF stimulation, and inhibition of p38 MAPK showed strong reduction of visfatin-induced effects. Directed as well as general fibroblast motility was increased by visfatin/PBEF-induced factors. The results of this study indicate that visfatin/PBEF is involved in synovial fibroblast activation by triggering fibroblast motility and promoting cytokine synthesis at central sites in RA synovium.

Adiponectin-mediated changes in effector cells involved in the pathophysiology of rheumatoid arthritis.

OBJECTIVE: Rheumatoid arthritis (RA) is associated with increased production of adipokines, which are cytokine-like mediators that are produced mainly in adipose tissue but also in synovial cells. Since RA synovial fibroblasts (RASFs), lymphocytes, endothelial cells, and chondrocytes are key players in the pathophysiology of RA, this study was undertaken to analyze the effects of the key adipokine adiponectin on proinflammatory and prodestructive synovial effector cells. METHODS: Lymphocytes were activated in part prior to stimulation. All cells were stimulated with adiponectin, and changes in gene and protein expression were determined by Affymetrix and protein arrays. Messenger RNA and protein levels were confirmed using semiquantitative reverse transcription-polymerase chain reaction (PCR), real-time PCR, and immunoassays. Intracellular signal transduction was evaluated using chemical signaling inhibitors. RESULTS: Adiponectin stimulation of human RASFs predominantly induced the secretion of chemokines, as well as proinflammatory cytokines, prostaglandin synthases, growth factors, and factors of bone metabolism and matrix remodeling. Lymphocytes, endothelial cells, and chondrocytes responded to adiponectin stimulation with enhanced synthesis of cytokines and various chemokines. Additionally, chondrocytes released increased amounts of matrix metalloproteinases. In RASFs, adiponectin-mediated effects were p38 MAPK and protein kinase C dependent. CONCLUSION: Our previous findings indicated that adiponectin was present in inflamed synovium, at sites of cartilage invasion, in lymphocyte infiltrates, and in perivascular areas. The findings of the present study indicate that adiponectin induces gene expression and protein synthesis in human RASFs, lymphocytes, endothelial cells, and chondrocytes, supporting the concept of adiponectin being involved in the pathophysiologic modulation of RA effector cells. Adiponectin promotes inflammation through cytokine synthesis, attraction of inflammatory cells to the synovium, and recruitment of prodestructive cells via chemokines, thus promoting matrix destruction at sites of cartilage invasion.

Furan oligomers and beta-carbolines from terrestrial streptomycetes.

2,5-Bis(hydroxymethyl)furan monoacetate (3) and 2,5-bis(hydroxymethyl)furan diacetate (4) were obtained as new natural products from an ethyl acetate extract of the terrestrial Streptomyces sp. isolate GW11/1695. Another Streptomyces isolate, GW21/1313, delivered a dimer (6) and a trimer (7) of (hydroxymethyl)furfural. The latter strain also produced 4-hydroxy-2-(5-(hydroxymethyl)furan-2-ylmethylene)-5-methylfuran-3-one (5), perlolyrin (8), and two new beta-carboline derivatives, 9 and 10. 2,5-Bis(hydroxymethyl)furan diacetate (4) exhibited weak cytotoxic activity against brine shrimp larvae.

Oceanibulbus indolifex gen. nov., sp. nov., a North Sea alphaproteobacterium that produces bioactive metabolites.

A water sample from the North Sea was used to isolate the abundant heterotrophic bacteria that are able to grow on complex marine media. Isolation was by serial dilution and spread plating. Phylogenetic analysis of nearly complete 16S rRNA gene sequences revealed that one of the strains, HEL-45T, had 97.4% sequence similarity to Sulfitobacter mediterraneus and 96.5 % sequence similarity to Staleya guttiformis. Strain HEL-45T is a Gram-negative, non-motile rod and obligate aerobe and requires sodium and 1-7% sea salts for growth. It contains storage granules and does not produce bacteriochlorophyll. Optimal growth temperatures are 25-30 degrees C. The DNA base composition (G+C content) is 60.1 mol%. Strain HEL-45T has Q10 as the dominant respiratory quinone. The major polar lipids are phosphatidyl glycerol, diphosphatidyl glycerol, phosphatidyl choline, phosphatidyl ethanolamine and an aminolipid. The fatty acids comprise 18 : 1omega7c, 18 : 0, 16 : 1omega7c, 16 : 0, 3-OH 10 : 0, 3-OH 12 : 1 (or 3-oxo 12 : 0) and traces of an 18 : 2 fatty acid. Among the hydroxylated fatty acids only 3-OH 12 : 1 (or 3-oxo 12 : 0) appears to be amide linked, whereas 3-OH 10 : 0 appears to be ester linked. The minor fatty acid components (between 1 and 7%) allow three subgroups to be distinguished in the Sulfitobacter/Staleya clade, placing HEL-45T into a separate lineage characterized by the presence of 3-OH 12 : 1 (or 3-oxo 12 : 0) and both ester- and amide-linked 16 : 1omega7c phospholipids. HEL-45T produces indole and derivatives thereof, several cyclic dipeptides and thryptanthrin. Phylogenetic analysis of 16S rRNA gene sequences and chemotaxonomic data support the description of a new genus and species, to include Oceanibulbus indolifex gen. nov., sp. nov., with the type strain HEL-45T (=DSM 14862T=NCIMB 13983T).

Helquinoline, a new tetrahydroquinoline antibiotic from Janibacter limosus Hel 1+.

The ethyl acetate extract of cultures of Janibacter limosus showed a high biological activity against bacteria, and fungi and delivered two new natural products, a tetrahydroquinoline derivative designated as helquinoline (1), and the N-acetylkynuramine (3a), along with other known secondary metabolites. The structure of 1 has been elucidated as 4-methoxy-2-methyl-1,2,3,4-tetrahydroquinoline-8-carboxylic acid on the basis of 1D and 2D NMR and mass spectra. The relative stereochemistry of the compound 1 was assigned as 2R*,4R* with the aid of coupling constants, NOESY correlation and by comparison with a related compound.

High-dose-rate brachytherapy in the treatment of recurrent and residual head and neck cancer.

OBJECTIVES/HYPOTHESIS: Interstitial and endocavitary brachytherapy are well-accepted kinds of radiotherapy that are commonly used in recurrent head and neck cancer. Most reports about brachytherapy in the successful treatment of head and neck tumors used low-dose-rate brachytherapy. There are only a few reports about high-dose-rate brachytherapy (HDRBT) in head and neck cancer patients. METHODS: After 10 years of experience with HDRBT with Ir 192, we have analyzed the results regarding response rates, survival time, and side effects. Between 1991 and 2000, 90 consecutive patients (68 men, 22 women) were treated with interstitial (68 patients) or intracavitary (22 patients) HDRBT in the head and neck area. Primary tumor locations were as follows: oropharynx (n = 26), tongue/floor of mouth (n = 22), nasopharynx (n = 10), nose/paranasal sinuses (n = 9), salivary glands (n = 5), hypopharynx (n = 5), CUP syndrome (n = 5), and others (n = 8). High-dose-rate brachytherapy was administered in 51 patients with recurrent disease and in 32 patients with residual tumor after primary radiochemotherapy. Seven patients were given exclusive HDRBT in a primary palliative situation. The single dose per fraction ranged from 1.5 to 7.5 Gy (median value, 5 Gy), and the total HDRBT dose ranged from 4.0 to 42.0 Gy (median value, 17.5 Gy). RESULTS: The overall remission rate was 81% with a 46% rate of complete remissions. We observed no change in or progression of tumor in 17 cases (19%). The rate of complete remissions (and median overall survival time) was different in the three therapy groups: in case of recurrent disease, 28% (6 mo); in case of residual tumor, 84% (25 mo); and in primary palliative brachytherapy, 0% (1 mo). Late toxicities III and IV (radiation treatment oncology group score) occurred in 6 of 90 (6.7%) patients. CONCLUSIONS: High-dose-rate brachytherapy proved to be an effective treatment modality in locoregional recurrent head and neck cancer. In cases with persistent or residual tumor after primary radiochemotherapy a local boost with brachytherapy can improve the chance of cure of tumor disease.