Limited influence of blunt aortic injuries on the outcome of polytraumatized patients: a matched pair analysis.

INTRODUCTION: Traumatic lesions of great vessels such as the aorta are life-threatening injuries. There is limited evidence about the influence of traumatic aortic injuries in multiple trauma patients in particular with regard to posttraumatic complications. The aim of this study was to evaluate the influence of blunt thoracic aortic injuries in multiple trauma patients compared to a multiple trauma cohort without this specific injury. In addition, the safety of Thoracic Endovascular Aortic Repair (TEVAR) in multiple trauma patients was analyzed. MATERIALS AND METHODS: A retrospective study was performed. We included all multiple trauma patients (ISS ≥ 16, age > 14 years) between 2005 and 2014 with (group BTAI) and without (group nBTAI) blunt traumatic aortic injuries who were treated at our level-1 trauma center. Demographic as well as clinical parameters were analyzed including injury pattern, mechanism of injury, posttraumatic complications such as ARDS, multiple organ dysfunction syndrome (MODS) and others. A matched pair analysis was performed by propensity score matching. RESULTS: In total, 721 patients were enrolled (group BTAI: n = 45; nBTAI: n = 676). In the initial study population, surgical intervention was done in n = 32 (71.1%) patients (TEVAR: n = 25; 78.1%), there was an increased AISChest and overall injury severity in group BTAI with associated significantly more posttraumatic complications in group BTAI. The matched pair analysis consisted of 42 patients per group. Beside an increased ventilation time, no significant differences were evident after the matching process. There was a trend to increased risk for SIRS using binary logistic regression analysis. CONCLUSIONS: Multiple trauma patients with blunt thoracic aortic injuries who are treated at a level-1 trauma center show a comparable outcome matched to their counterparts without aortic injuries. Our study confirms that using TEVAR in polytraumatized patients is a safe procedure. In all patients treated with TEVAR, there were no procedure-related complications, especially no neurological deficit.

Infant formula containing galacto-and fructo-oligosaccharides and Bifidobacterium breve M-16V supports adequate growth and tolerance in healthy infants in a randomised, controlled, double-blind, prospective, multicentre study.

The objective of the present study was to evaluate the growth and tolerance in healthy, term infants consuming a synbiotic formula with daily weight gain as the primary outcome. In a randomised, controlled, double-blind, multicentre, intervention study infants were assigned to an extensively hydrolysed formula containing a specific combination of Bifidobacterium breve M-16V and a prebiotic mixture (short-chain galacto-oligosaccharides and long-chain fructo-oligosaccharides in a 9:1 ratio; scGOS/lcFOS; synbiotic group), or the same formula without this synbiotic concept for 13 weeks (control group). Anthropometry, formula intake, tolerance, stool characteristics, blood parameters, faecal microbiota and metabolic faecal profile were assessed. Medically confirmed adverse events were recorded throughout the study. Equivalence in daily weight gain was demonstrated for the intention-to-treat (ITT) population (n 211). In the per-protocol (PP) population (n 102), the 90 % CI of the difference in daily weight gain slightly crossed the lower equivalence margin. During the intervention period, the mean weight-for-age and length-for-age values were close to the median of the WHO growth standards in both groups, indicating adequate growth. The number of adverse events was not different between both groups. No relevant differences were observed in blood parameters indicative for liver and renal function. At 13 weeks, an increased percentage of faecal bifidobacteria (60 v. 48 %) and a reduced percentage of Clostridium lituseburense/C. histolyticum (0·2 v. 2·6 %) were observed in the synbiotic group (n 19) compared with the control group (n 27). In conclusion, this study demonstrates that an extensively hydrolysed formula with B. breve M-16V and the prebiotic mixture scGOS/lcFOS (9:1) supports an adequate infant growth.

TRIM32-dependent transcription in adult neural progenitor cells regulates neuronal differentiation.

In the adult mammalian brain, neural stem cells in the subventricular zone continuously generate new neurons for the olfactory bulb. Cell fate commitment in these adult neural stem cells is regulated by cell fate-determining proteins. Here, we show that the cell fate-determinant TRIM32 is upregulated during differentiation of adult neural stem cells into olfactory bulb neurons. We further demonstrate that TRIM32 is necessary for the correct induction of neuronal differentiation in these cells. In the absence of TRIM32, neuroblasts differentiate slower and show gene expression profiles that are characteristic of immature cells. Interestingly, TRIM32 deficiency induces more neural progenitor cell proliferation and less cell death. Both effects accumulate in an overproduction of adult-generated olfactory bulb neurons of TRIM32 knockout mice. These results highlight the function of the cell fate-determinant TRIM32 for a balanced activity of the adult neurogenesis process.

Prevention of vascular graft infections with antibiotic graft impregnation prior to implantation: in vitro comparison between daptomycin, rifampin and nebacetin.

OBJECTIVE: To compare the in vitro efficacy of graft impregnation with nebacetin versus rifampin versus daptomycin against vascular graft infections caused by Staphylococcus epidermidis and Staphylococcus aureus and nebacetin versus rifampin against Pseudomonas aeruginosa and Escherichia coli. MATERIALS: Twenty-three Dacron-grafts (1 cm2) for each micro-organism were microbiologically tested and eight grafts per antibiotic underwent viability tests against human umbilical vein endothelial cells (ECs). Fifteen grafts (5/antibiotic agent) underwent 15 min impregnation and contamination with 4 ml bacterial solution (optical density (OD (600 nm)): 0.20 ± 0.02). After 24-h-incubation, all grafts were washed with phosphate-buffered saline and underwent sonification to release viable adherent bacteria. OD (600 nm) of the solution was measured. Afterwards, six 1:10 dilution steps took place and colony-forming units (CFUs) were counted. RESULTS: Nebacetin showed comparable efficacy to daptomycin against Gram-positive bacteria. Both eradicated more efficiently S. epidermidis than rifampin (daptomycin:0, rifampin:5 ± 7.3, nebacetin:0 CFU ml(-1), P = 0.0003). All antibiotics showed comparable antibacterial activity against S. aureus. Nebacetin was more efficient than rifampin to eradicate Gram-negative organisms (P. aeruginosa: rifampin:1308 ± 252, nebacetin:8 ± 8 CFU ml(-1), P = 0.01, E. coli: rifampin:294 ± 159, nebacetin:0.2 ± 0.5 CFU ml(-1), P = 0.001), while only rifampin was toxic against ECs (daptomycin:30.88 ± 5.44, rifampin:5.13 ± 5.08, nebacetin:28.50 ± 3.82 ECs/field, P = 0.0003). CONCLUSIONS: Nebacetin showed excellent in vitro antibacterial activity against both Gram-positive and -negative pathogens representing an effective candidate for vascular graft impregnation.

CT scanning the early days.

CT scanning has become an established diagnostic tool within the radiology department. This article covers some of the history of the development and early days of CT scanning. It is based upon the lecture given on the Memorial Day for Sir Godfrey Hounsfield during the British Institute of Radiology President's Conference 2005.

Distribution of HPV 53, HPV 73 and CP8304 in genital epithelial lesions with different grades of dysplasia.

To characterize the risk of malignant progression of cervical epithelial lesions associated with human papillomavirus (HPV) types of yet unknown oncogenic potential the prevalences of these HPVs in different cervical epithelial lesions of 809 patients were determined. HPV types 53, 73, and CP8304 were detected in genital specimens of 16, 22, and 12 of the patients, respectively. The ratio of prevalence in high grade dysplastic lesions or cancers and low grade dysplastic lesions or normal specimens was calculated and compared to corresponding values of well known high-risk (HR) and low-risk (LR) HPVs. For HPV 6, 11, 16, 18, 35, and 73 a ratio of 0.1, 0.2, 5.9, 6.5, 2.5, and 2.4, respectively, was calculated. The ratios of HPV53 and CP8304 were less than 1. Moreover, in contrast to HPV73, these viruses have never been detected in cancer specimens. Thus, HPV53 and CP8304 infections are probably not associated with a high risk of carcinogenesis, while HPV73 could be another HR-HPV type.

Low grade gliomas treated with adjuvant radiation therapy in the modern imaging era.

The purpose of this study is to evaluate tumor control and failure patterns in patients with low grade gliomas treated with surgery and conventional adjuvant radiation therapy. Twenty-eight patients with low grade gliomas (7 grade I, 21 grade II) were retrospectively evaluated. Extent of resection was gross total (3), subtotal (17), and biopsy alone (8). All grade I tumors underwent subtotal resection. Median radiation therapy dose was 54 Gy delivered to localized fields. Tumor control and patterns of failure were determined from follow-up computed tomography and/or magnetic resonance scans. Median follow-up was 86 months (range, 2.4-177 months). Thirteen patients (46%) (four grade I, nine grade II) developed tumor progression. The 5-year actuarial progression-free survival rates for grade I and grade II patients were 86% and 51%, respectively. Corresponding 5-year actuarial survival rates were 100% and 70%. All recurrences were within the treated volume. Our results reveal that conventional adjuvant radiation therapy is associated with high rates of local tumor progression in both grade II and incompletely resected grade I low grade gliomas. Alternative strategies need to be explored in these patients in an effort to improve tumor control and outcome.

Structure of the 13-fold symmetric portal protein of bacteriophage SPP1.

We have determined the three-dimensional structure of bacteriophage SPP1 portal protein (gp6) using electron microscopy at liquid-helium temperatures and angular reconstitution. The 13-fold symmetric gp6 oligomer is a turbine-shaped structure with three distinct regions: a conical stem with a central channel; the turbine wings region; and a fringe of small 'tentacles' at the end of the channel exposed to the viral head interior. The tentacle region appears flexible and may be associated with a particular function - sensing when the correct amount of DNA has been packaged. The three-dimensional structure of the gp6 SizA mutant, which packages a smaller chromosome, reveals significant differences in that region.

Stress-induced recrystallization of a protein crystal by electron irradiation.

Ordering of a system of particles into its thermodynamically stable state usually proceeds by thermally activated mass transport of its constituents. Particularly at low temperature, the activation barrier often hinders equilibration--this is what prevents a glass from crystallizing and a pile of sand from flattening under gravity. But if the driving force for mass transport (that is, the excess energy of the system) is increased, the activation barrier can be overcome and structural changes are initiated. Here we report the reordering of radiation-damaged protein crystals under conditions where transport is initiated by stress rather than by thermal activation. After accumulating a certain density of radiation-induced defects during observation by transmission electron microscopy, the distorted crystal recrystallizes. The reordering is induced by stress caused by the defects at temperatures that are low enough to suppress diffusive mass transport. We propose that this defect-induced reordering might be a general phenomenon.

Association of rare human papillomavirus types with genital premalignant and malignant lesions.

Due to the limited number of reports concerning their association with particular dysplastic and neoplastic lesions, the oncogenic potential of so-called rare or novel human papillomavirus (HPV) types is still unclear. Cytologic smears or biopsy specimens from 538 patients were analyzed for dysplastic or neoplastic lesions and HPV infection. The HPV detection and typing system utilized allowed identification of all mucosal HPVs amplifiable by L1 polymerase chain reaction. Considering only patients infected with a single HPV type (n = 329), rare or novel HPVs (HPV-59, HPV-61, HPV-62, HPV-66, HPV-70, HPV-73, MM4, MM7, MM8, CP6108, and CP8304) were detected in 28% of normal specimens (n = 46), none of condylomatous lesions (n = 44), 12% of low-grade squamous intraepithelial lesions (SILs) (n = 42), 8% of high-grade SILs (n = 142), and 4% of cervical cancers (n = 54). Prevalence and oncogenic potential of distinct rare HPV types seems to be higher than previously assumed.

Non-helical perturbations of the flagellar filament: Salmonella typhimurium SJW117 at 9.6 A resolution.

Using a liquid-helium-cooled superconducting electron cryo-microscope, we obtained low-dose images of negatively stained preparations at 4 K and collected structural data to 1/9.6 -1 for flagellar filaments from the strain SJW117 of Salmonella typhimurium (serotype gt). The subunits of this left-handed, straight filament are non-helically perturbed in a pairwise manner. The perturbation corresponds to an alternating conformation in every other row of subunits. These are the 5-start rows and, necessarily, the resulting structure has a seam. The perturbation is not confined to the outside but extends into the structure. We separated the non-symmetric and symmetric parts of the structural data and generated a three-dimensional reconstruction from the latter. The resulting density map is a structure similar in domain organization to the left-handed filament of S. typhimurium SJW1660. Filtered images generated from the non-symmetric component show an ordered and polar structure. The nature of the perturbation was analyzed by model building using a sphere to represent the subunit at low resolution. A lateral shift of approximately 10 degrees mimics the perturbation.

Mononeuropathy multiplex due to infiltration of lymphoma in hematologic remission.

We report a case of progressive mononeuropathy multiplex in a patient with lymphoma in hematologic remission. At the time of presentation there was no evidence of meningeal or central nervous system metastasis. At autopsy, extensive infiltration of tumor cells was found in both femoral nerves. We review the literature pertaining to multifocal malignant lymphoid infiltration of peripheral nerves, which can occur during hematologic remission or in the absence of any evidence of systemic lymphoma.

Thymidylate synthase expression and response to neoadjuvant chemotherapy in patients with advanced head and neck cancer.

BACKGROUND: Thymidylate synthase (TS), an essential enzyme in DNA synthesis, is a target for the fluoropyrimidines, an important group of antineoplastic agents used widely in the treatment of head and neck cancer. PURPOSE: We evaluated relationships between the level and/or pattern of tumor TS expression and response to fluorouracil (5-FU)-based neoadjuvant chemotherapy in patients with advanced head and neck cancer. METHODS: Tumor specimens from 86 patients were available for this retrospective analysis. The patients were enrolled in four consecutive phase II studies that tested combinations of 5-FU, leucovorin, and cisplatin with or without added methotrexate plus piritrexim or interferon alfa-2b (IFN alpha-2b). TS protein expression in the tumors was assessed by use of the TS 106 monoclonal antibody and standard immunohistochemical staining techniques. TS immunostaining was classified according to its level of intensity (TS 0-1 = low, TS 2 = intermediate, and TS 3 = high) and according to its extent (focal pattern = less than 25% of tumor cells positive; diffuse pattern = greater than or equal to 25% of tumor cells positive). Data from 79 patients were available for an analysis of tumor TS expression and patient/tumor characteristics; 70 patients were assessable for their response to neoadjuvant chemotherapy. RESULTS: There was a statistically significant association between the level of tumor TS expression and the degree of tumor differentiation; a higher proportion of patients whose tumors exhibited TS 0-1 immunostaining had undifferentiated or poorly differentiated tumors than patients whose tumors exhibited TS 2 or TS 3 immunostaining (P = .04, Jonckheere-Terpstra trend test). Among the 70 patients who were assessable for response to neoadjuvant chemotherapy, TS 3 tumor immunostaining was associated with a lower rate of complete response (i.e., complete disappearance of clinically detectable disease for a minimum of 4 weeks from time of initial determination) than was TS 2 or TS 0-1 immunostaining, but this association was not statistically significant (P = .09, exact trend test); among the 39 patients who were treated with regimens that included 5-FU, leucovorin, cisplatin, and IFN alpha-2b, this inverse association between TS immunostaining intensity and response was statistically significant (P = .02, exact trend test). Tumor TS immunostaining intensity and overall survival were not found to be associated. Patients with tumors exhibiting a focal pattern of TS immunostaining have experienced significantly longer survival than patients with tumors exhibiting a diffuse pattern; for the 53 patients with diffuse tumor TS immunostaining, the median survival was 24.7 months, whereas the median survival has not yet been reached for the 22 patients with focal tumor TS immunostaining (P = .04, two-tailed logrank test). However, the survival advantage for the focal versus diffuse TS immunostaining pattern was limited to patients whose tumors also exhibited a TS 3 level of immunostaining intensity. CONCLUSIONS AND IMPLICATIONS: Characterization of tumor TS expression may be of value in identifying patients with advanced head and neck cancer who would benefit from fluoropyrimidine-based neoadjuvant chemotherapy.

Solitary fibrous tumor of the orbit.

PURPOSE: We studied a case of solitary fibrous tumor of the orbit in a 75-year-old man. METHODS: The patient had painless, slowly progressive proptosis of eight months' duration. He underwent magnetic resonance imaging, which showed a well-circumscribed retrobulbar mass. The tumor was excised. RESULTS: Examination of the tumor disclosed haphazardly arranged spindle cells alternating with collagenous, hypocellular areas in a richly vascular background without necrosis. Immunoperoxidase stains showed characteristic expression of CD34 and vimentin. CONCLUSION: Solitary fibrous tumor can infrequently involve the orbit and may recur locally and metastasize, necessitating long-term follow-up.

Lipid location in deoxycholate-treated purple membrane at 2.6 A.

A high resolution projection at 2.6 A of deoxycholate-treated purple membrane using only images has been obtained with a 200 keV FEG microscope operated at liquid helium temperature. Examination of this high quality map has allowed the following conclusions to be made: Comparison between the internal structure of the trimers of the native and the deoxycholate-treated crystal forms shows that almost every detail of the structure at high resolution is identical. The cell dimension change from 62.4 A to 57.9 A is accompanied by a loss of about half the normal lipids and a 2 degrees anticlockwise rotation of the trimer as a rigid body. Three of the lipids per bacteriorhodopsin molecule remain in identical positions relative to the trimer. In addition, from the projection map together with a packing analysis using the atomic model for bacteriorhodopsin, space for three further lipids has been identified making a total of six lipids per bacteriorhodopsin molecule in this crystal form. Finally, the surprisingly small rotation of the trimer between the two crystal forms with completely different Van der Waals contacts suggest that the crystals are held together by strong, long-range electrostatic interactions.

Definitive identification of a gene that confers resistance against Toxoplasma cyst burden and encephalitis.

Control of resistance to cyst burden following per-oral infection with Toxoplasma gondii has been mapped previously to a region of mouse chromosome 17 of approximately 140 kb. This region is contiguous with and contains the class I gene, Ld. Resistance to development of toxoplasmic encephalitis has also been reported to be controlled by genes in this region of H-2. TNF-alpha, D and L genes, as well as unidentified genes, are also in this region. The work described here was performed to identify definitively the gene(s) in this 140 kb region that confers resistance to cysts and encephalitis. The study demonstrates that relative resistance to T. gondii organisms and cyst burden in brain, and toxoplasmic encephalitis, 30 days following per-oral T. gondii infection is correlated absolutely with the presence of the Ld gene in inbred, recombinant, mutant and C3H.Ld transgenic mice. Mice with the Ld gene had lower cyst burdens and less encephalitis than those without the Ld gene. Specifically, 30 days after infection mice with the Ld gene had minimal perivascular inflammation and meningeal inflammation and very few Toxoplasma cysts or organisms in immunoperoxidase-stained preparations of their brains. Mice without the Ld gene had a similar pattern of inflammation, but in addition they had collections of inflammatory cells in the brain parenchyma. Free tachyzoites were found within these foci of inflammation and cysts were present in these areas as well as in contiguous areas without inflammatory cells. There were CD4+ and CD8+ T lymphocytes in the areas of inflammation and throughout the brain parenchyma. Mice that were resistant to cysts and encephalitis had little detectable brain cytokine mRNA expression, while mice that were susceptible had elevated levels of mRNA for a wide range of cytokines, consistent with their greater amounts of inflammation. The present work definitively demonstrates that a Ld-restricted response decreases the number of organisms and cysts within the brain and thereby limits toxoplasmic encephalitis and levels of interferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha), interleukin-2 (IL-2), IL-6, IL-10, transforming growth factor-beta (TGF-beta), IL-1 alpha, IL1 beta and macrophage inhibiting protein (MIP) mRNA in the brain 30 days after per-oral infection.

An atomic model for the structure of bacteriorhodopsin, a seven-helix membrane protein.

A three-dimensional map of bacteriorhodopsin has been obtained, at near-atomic resolution, by collecting and analysing electron diffraction patterns and electron micrographs from crystals of bacteriorhodopsin preserved at very low temperatures. The map shows a resolution of 3.5 degrees in a direction parallel to the plane of the membrane, but poorer resolution perpendicular. It shows many features well resolved from the main density of the seven alpha-helices, which we interpret as the bulky sidechains of tyrosine, phenylalanine and tryptophan, as well as a very dense feature, which is the beta-ionone ring of the retinal chromophore. Using these bulky side chains as starting points and taking account of bulges of density for the smaller side chains such as leucine, we built an atomic model for the residues between 8 and 225. There are 21 amino acids from all 7 helices surrounding the retinal and 26 amino acids contributed by 5 helices that form the proton channel. Ten of the amino acids in the middle of the proton channel are also part of the retinal-binding site. The model provides a useful basis for considering the mechanism of proton pumping and in the interpretation of other experimental data. In particular, the model suggests that the pK changes in the Schiff base must act as the means by which light energy is converted to proton pumping through the channel. Asp-96 is on the pathway from the cytoplasm to the Schiff base and asp-85 on the pathway from the Schiff base to the extracellular surface. The experimental map and the building of the model of the structure will be described, as well as our interpretation of the structural basis of the mechanism.