A fast B1-mapping method for the correction and normalization of magnetization transfer ratio maps at 3 T

In neuroimaging, there is increasing interest in magnetization transfer (MT) techniques which yield information about bound water protons. One of the main applications is the investigation of the myelin integrity in the central nervous system (CNS). However, several problems may arise, in particular at high magnetic field strengths: B1 inhomogeneities may yield deviations of the MT saturation angle and thus non-uniformities of the measured MT ratio (MTR). This effect can be corrected for but requires in general additional time consuming B1 mapping. Furthermore, increased values of the specific absorption rate (SAR) may require a reduction of the saturation angle for individual subjects, impairing comparability of results.In this work, a B1 mapping method based on magnetization-prepared FLASH with slice selective preparation and excitation pulses and correction for relaxation effects is presented, yielding B1 maps with whole brain coverage, an in-plane resolution of 4 mm, a slice thickness of 3 mm, and a clinically acceptable duration of 46 s. The method is tested both in vitro and in vivo and applied in a subsequent in vivo study to show that MTR values in human brain tissue depend approximately linearly on the preparation angle, with a slope similar to values reported for 1.5 T. Calibration data and B1 maps are applied to B1 inhomogeneity corrections of MTR maps. Subsequently, it is shown that B1-corrected MTR maps acquired at reduced preparation angles due to individual SAR restrictions can be normalized, allowing for a direct comparison with maps acquired at the full angle.     

Antimycobacterial activity of diphenylpyraline derivatives

2-Substituted derivatives of diphenylpyraline and their 1-phenyl and 1-phenethyl analogues have been prepared in several steps from dihydropyridine-2(1H)-thiones. The structures of all new compounds have been confirmed by NMR spectroscopy. Their activity against Mycobacterium tuberculosis H(37)Rv as well as their cytotoxicity against human cells (HEK-293) have been determined via in vitro assays. The antimycobacterial potency was in general increased by substitution in ring position 2. The most promising modifications were a 2-isopropyl derivative and a 1,2-diphenyl analogue.     

Domestic cat allergen and allergic sensitisation in young children

Studies have presented conflicting associations between cat allergen exposure and sensitisation and atopic disease. We therefore investigated the association between the observed domestic cat allergen level and cat sensitisation in young children in four study populations from three European countries. We recruited children from a nested case-control study, which is composed of four ongoing birth cohorts conducted in three European countries. Children at 2-4 years of age in the four cohorts who were sensitised to cat allergens (n=106) were compared with 554 non-sensitised children (controls). House dust samples were collected when the children were 5 to 7 years old, and cat allergen levels were measured in ng/g dust and ng/m(2) surface area. In the German study population we found a positive association between domestic cat allergen in house dust and cat sensitisation (OR (CI)=3.01 (1.16, 7.99)) while in the Swedish study population, we found a negative association (OR (CI)=0.41 (0.16, 0.98)). No association was found in the Dutch study population (OR (CI)=0.83 (0.22, 2.93)). Looking into the family history of cat keeping, we found the lowest prevalence of cat sensitisation in children who were cat owners at the age of blood sampling (11%) and the highest prevalence was found in those who have had a cat but not anymore, at the age of blood sampling (41%). The mixed results may be explained by differences in age and avoidance patterns.     

Comparison of setup accuracy and intrafraction motion using stereotactic frame versus 3-point thermoplastic mask-based immobilization for fractionated cranial image guided radiation therapy

PurposeProspectively compare patient setup accuracy and intrafraction motion of a standard 3-point thermoplastic mask with the Gill-Thomas-Cosman relocatable stereotactic frame, during fractionated cranial radiation therapy using the ExacTrac system (Brainlab AG Feldkirchen, Germany) for daily online correction.Methods and MaterialsThe number of fractions with all postcorrection and post-treatment errors < 2 mm was assessed in 21 patients undergoing fractionated stereotactic radiation therapy (13 frame setup, 8 mask setup) using daily online correction. Achievable patient setup accuracy and total intrafraction motion were evaluated. The relative contributions of movement during floor rotation and patient movement to intrafraction motion were calculated.ResultsWith daily online correction, patient setup margins can be reduced from 1, 5, and 4 mm in the lateral, longitudinal, and vertical axes for mask setup and from 1-2, 2, and 1 mm, respectively, for frame setup to < 1 mm isotropically for either immobilization system. Intrafraction movement was small for frame setup (mean [SD], ? 0.3 [0.3], ? 1.1[0.4], and ? 0.2 [0.6] in lateral, longitudinal and vertical axes, respectively; maximum, ? 2.7 mm [longitudinal axis]), and mask-setup (mean [SD], ? 0.4 [0.5], ? 0.8 [0.7], and 0.0 [0.3], respectively; maximum, ? 2.0 mm [longitudinal axis]) and is mainly due to floor rotation. Postcorrection and post-treatment errors were all < 2 mm in 95% and 99% of fractions in the mask and frame, respectively, meeting the criteria for a 3-mm clinical target volume-planning target volume margin for either immobilization method.ConclusionsDaily online correction can compensate for less precise immobilization and permits stereotactic margins to be used for standard thermoplastic masks without the need for specialized mask systems.     

In vitro activity of rilopirox against fluconazole-susceptible and fluconazole-resistant Candida isolates from patients with HIV infection

The in vitro antifungal activity of the new hydroxypyridone antimycotic rilopirox has been evaluated against 38 fluconazole-susceptible and -resistant clinical isolates of Candida albicans together with other Candida species isolated from patients with human immunodeficiency virus (HIV) infection and oropharyngeal candidosis. Minimum inhibitory concentrations (MICs) of both rilopirox and fluconazole were measured by a microdilution method using high-resolution medium supplemented with asparagine and glucose at pH 7.0. In comparison, an agar dilution technique was carried out for susceptibility testing of the antifungal agents. Rilopirox was found to be able to inhibit growth of all clinical yeast isolates. The rilopirox MICs at which 50% and 90% of strains were inhibited (MIC50 and MIC90 respectively), as determined by the microdilution method, were 4 and 8 micrograms ml-1 respectively. The highest MIC values for rilopirox using microdilution and the agar dilution method were 32 or 25 micrograms ml-1 respectively. On the other hand, for fluconazole, the MIC50 and MIC90 achieved were 0.5 and 128 micrograms ml-1, respectively, which means that the MIC90 value of fluconazole was 16-fold higher than that of rilopirox. Using the agar dilution technique, the MIC values of rilopirox were in the range 0.006-25 micrograms ml-1 with a median of 3.12 micrograms ml-1. For fluconazole, the MIC90 value was four-fold higher than that for rilopirox, indicating a considerable proportion of yeast strains with high MICs of 100 micrograms ml-1, suggesting in vitro resistance to this azole antifungal. All strains with diminished fluconazole susceptibility were susceptible to rilopirox. Even Candida krusei and Candida glabrata exhibited good in vitro susceptibility to rilopirox. Therefore, this new antifungal agent may be used as an alternative not only in the treatment of vaginal candidosis, but also in oropharyngeal Candida infections, e.g. in AIDS patients.     

Prophylactic corticosteroid use prevents engraftment syndrome in patients after autologous stem cell transplantation

Engraftment syndrome (ES) following autologous stem cell transplantation (ASCT) at the time of neutrophil recovery may comprise fever, rash, pulmonary edema, or diarrhea. Usually, ES is easily manageable using corticosteroids but may prolong hospitalization. In two consecutive cohorts of subsequent patients with myeloma, lymphomas, and testicular/germ cell cancer, we assessed the benefit of corticosteroid use to prevent incidence and severity of ES following ASCT. Whereas Cohort A (82 patients) received no prophylactic corticosteroids, corticosteroids (4 mg dexamethasone oral daily) were started in Cohort B (60 patients) at day +9 until day +13 following ASCT. Steroid prophylaxis significantly reduced the incidence of ES (6/60; 10% vs. 33/82; 40%; p < 0.001). Hospitalization duration was longer in patients with ES than in patients without ES within both cohorts (in Cohort A: p = 0.007; and B: p = 0.011), but did not differ significantly between cohorts A and B. Finally, in Cohort A, there was a trend to an inferior 2‐year overall survival rate in patients without ES compared to patients with ES (p = 0.067), but definite conclusions are not yet allowed. Our results suggest that corticosteroid prophylaxis from days +9 to +13 following ASCT significantly reduces the risk of ES and shortens hospitalization duration.     

GAS64, the first amplified and putative non-translated gene.

Gene amplification occurs frequently in human glioblastomas. We report the amplification and expression analysis of glioma amplified sequence 64 (GAS64) which was recently identified by microdissection mediated cDNA capture from the amplicon at 12q13-15. Herein we analyzed primary tumor tissues for amplification frequency and found amplification of GAS64 in 5 out of 49 glioblastomas. The amplification frequency of 10% for GAS64 found among glioblastomas is comparable to the frequency described for other genes from the 12q13-15 amplicon. To isolate the full-length cDNA of GAS64, we performed cDNA library screening and RACE. Sequence analysis of the gene revealed no open reading frame longer than 191 bp suggesting that the RNA may function as a non-translated RNA. Non-translated RNAs have been reported to function on the RNA level as regulators of gene expression. Northern hybridization of GAS64 revealed an increased GAS64 expression in many human glioblastomas with and without GAS64 gene amplification. This is the first report on an amplified and expressed gene with a short open reading frame (ORF). GAS64 may be a candidate gene for regulating gene expression in glioblastomas at the RNA level, possibly through expression of a non-translated RNA.