Bladder dose accumulation based on a biomechanical deformable image registration algorithm in volumetric modulated arc therapy for prostate cancer.

Variations in bladder position, shape and volume cause uncertainties in the doses delivered to this organ during a course of radiotherapy for pelvic tumors. The purpose of this study was to evaluate the potential of dose accumulation based on repeat imaging and deformable image registration (DIR) to improve the accuracy of bladder dose assessment. For each of nine prostate cancer patients, the initial treatment plan was re-calculated on eight to nine repeat computed tomography (CT) scans. The planned bladder dose-volume histogram (DVH) parameters were compared to corresponding parameters derived from DIR-based accumulations as well as DVH summation based on dose re-calculations. It was found that the deviations between the DIR-based accumulations and the planned treatment were substantial and ranged (-0.5-2.3) Gy and (-9.4-13.5) Gy for D(2%) and D(mean), respectively, whereas the deviations between DIR-based accumulations and DVH summation were small and well within 1 Gy. For the investigated treatment scenario, DIR-based bladder dose accumulation did not result in substantial improvement of dose estimation as compared to the straightforward DVH summation. Large variations were found in individual patients between the doses from the initial treatment plan and the accumulated bladder doses. Hence, the use of repeat imaging has a potential for improved accuracy in treatment dose reporting.

Whole-heart imaging using undersampled radial phase encoding (RPE) and iterative sensitivity encoding (SENSE) reconstruction.

Whole-heart isotropic nonangulated cardiac magnetic resonance (CMR) is becoming an important protocol in simplifying MRI, since it reduces the need of cumbersome planning of angulations. However the acquisition times of whole-heart MRI are prohibitive due to the large fields of view (FOVs) and the high spatial resolution required for depicting small structures and vessels. To address this problem, we propose a three-dimensional (3D) acquisition scheme that combines Cartesian sampling in the readout direction with an undersampled radial scheme in the phase-encoding plane. Different undersampling patterns were investigated in combination with an iterative sensitivity encoding (SENSE) reconstruction and a 32-channel cardiac coil. Noise amplification maps were calculated to compare the performance of the different patterns using iterative SENSE reconstruction. The radial phase-encoding (RPE) scheme was implemented on a clinical MR scanner and tested on phantoms and healthy volunteers. The proposed method exhibits better image quality even for high acceleration factors (up to 12) in comparison to Cartesian acquisitions.

Chelation of molybdenum in Medicago sativa (alfalfa) grown on reclaimed mine tailings.

Extraction and analytical procedures were developed from 1999 to 2005 for the chemical investigation of molybdenum (Mo) in aerial portions of alfalfa ( Medicago sativa L.) grown on a reclaimed mine tailings site at the Highland Valley Copper Mine in British Columbia, Canada. The purification procedures were guided by colorimetric analyses specific for Mo. The Mo levels in freeze-dried plant samples exceeded 100 ppm, which is more than 20 times the maximum level recommended for livestock feed. In contrast to previous work, which detected the inorganic molybdate anion (MoO4(2-)) in alfalfa from the site, the present study identified the major pool of Mo as a chelate bound to malic acid in five sources of plant material. However, the inorganic form of Mo was characterized in aqueous tailings samples, but once imbibed by vegetation, the anion was chelated to the alpha-hydroxy organic acid. Synthetic chelates were synthesized to differentiate the Mo-malate complex from the Mo-citrate by 95Mo NMR. Crystal structure of the synthetic Mo-malate determined that the Mo was bound to two malato ligands as Na 2[MoO2(malate) 2] x 5H2O, which confirmed the structure of the isolates deduced by 95Mo NMR. The chelation of Mo at the site may well explain the apparent lack of long-term clinical effects in cattle grazing the site.

Accelerating the nonequispaced fast Fourier transform on commodity graphics hardware.

We present a fast parallel algorithm to compute the nonequispaced fast Fourier transform on commodity graphics hardware (the GPU). We focus particularly on a novel implementation of the convolution step in the transform as it was previously its most time consuming part. We describe the performance for two common sample distributions in medical imaging (radial and spiral trajectories), and for different convolution kernels as these parameters all influence the speed of the algorithm. The GPU-accelerated convolution is up to 85 times faster as our reference, the open source NFFT library on a state-of-the-art 64 bit CPU. The accuracy of the proposed GPU implementation was quantitatively evaluated at the various settings. To illustrate the applicability of the transform in medical imaging, in which it is also known as gridding, we look specifically at non-Cartesian magnetic resonance imaging and reconstruct both a numerical phantom and an in vivo cardiac image.

In situ diagnostics of the decomposition of silacyclobutane on a hot filament by vacuum ultraviolet laser ionization mass spectrometry.

The gas-phase reaction products of silacyclobutane (SCB) and 1, 1-dideuterio-silacyclobutane (SCB-d(2)) from a hot-wire chemical vapor deposition (HWCVD) chamber were diagnosed in situ using vacuum ultraviolet (VUV) laser single-photon ionization (SPI) coupled with time-of-flight (TOF) mass spectrometry. The SCB molecule was found to decompose at a filament temperature as low as 900 degrees C. Both Si- (silylene, methylsilylene, and silene) and C-containing (ethene and propene) species were produced from the SCB decomposition on the filament. Ethene and propene were detected by the mass spectrometer. It is demonstrated that the formation of ethene is favored over that of propene. The experimental study of hot-wire decomposition of SCB-d(2) shows that propene is most likely produced by a process that is initiated by a 1,2-H(D) migration to form n-propylsilylene, followed by an equilibration with silacyclopropane, which then decomposes to propene. The detection of ethene in our experiment indicates that a competitive route of fragmentation exists for SCB decomposition on the filament. It has been shown that this competitive route occurs without H/D scrambling. The highly reactive silylene, silene, and methylsilylene species produced from SCB decomposition underwent either insertion reactions into the Si-H bonds of the parent molecule or pi-type addition reaction across the double and triple CC bonds. The dimerization product of silene, 1,3-disilacyclobutane, at m/z = 88 was also observed.

The historic camphenyl cation: a detailed structure evaluation including solvation energy calculations.

The structure of the camphenyl cation 1 has been studied in detail, using both experimental and computational approaches. Like others, we find only one structure on the camphenyl-isobornyl cation PE surface, but this single structure shows some unusual features. These include a very soft PE surface for movement along the C2-C6 axis (a nonbonding distance in a classical description of the cation), and a result of this is that very high computational methods (optimization at MP4 or QCI levels) are required in order to get structural minima that "fit" the experimental data. This PE surface has been probed computationally using fixed C2-C6 distances, and when one also calculates chemical shifts for these "fixed" structures, one sees calculated (13)C NMR chemical shifts for the C2 carbon that are hugely dependent on this fixed distance value, giving near-linear slopes of ca. 25 ppm/0.1 A distance change. Since this distance can vary over at least 0.6 A with relatively small calculated energy changes, there is a total range of ca. 150 ppm involved here. In a second part of this work, and in response to a recent paper in which the historic Meerwein "carbocation intermediate" proposal was rejected, we have calculated solvation energies (SCI-PCM method) for four carbocation systems, including 1. We find carbocation solvation energies (epsilon = 10 "solvent") of 45-53 kcal/mol, and where comparison can be made, the data correlate well with the literature. On the basis of these results, we re-affirm the Meerwein "carbocation" mechanism, but in order to accommodate only a single carbocation intermediate, we offer a description that amounts to a subtle variation of both the nonclassical ion proposal and Meerwein's "two cation" mechanism, namely that the camphenyl cation, 1, as a ground-state structure, can be described as only very weakly interacting in the C2-C6 bridging sense, but that the PE surface along this "bond" is so shallow that an energy input of only 4-6 kcal/mol can produce a bridged "structure". This mechanism explains the preferred formation of exo products in both the camphenyl and isobornyl systems, isotopic exchange of chloride in camphenyl chloride, and it allows for partial racemization of the camphenyl-isobornyl products in the reaction.

Purification and characterization of molybdenum species from Medicago sativa (alfalfa) grown on mine tailings.

Extraction, purification, and identification procedures were developed for the chemical investigation of molybdenum (Mo) in freeze-dried aerial portions of alfalfa (Medicago sativa L.) collected from a reclaimed tailings pond at the Highland Valley Copper mine in British Columbia. The purification procedures were guided by ICP and colorimetric analyses. The methods included development of an efficient aqueous extraction protocol, sample cleanup by partitioning against n-butanol, and filtration through diatomaceous earth. Further purification was achieved by anion-exchange chromatography, elution with aqueous NaCl, and desalting by gel filtration. Final purification of the Mo-containing fraction was carried out using preparative anion-exchange HPLC. Molybdenum was found to be present in its purified form as the molybdate anion (MoO(4)(2-)) primarily on the basis of multinuclear ((1)H, (13)C, and (95)Mo) NMR studies.

Origin of diastereofacial selectivity in tertiary 2-adamantyl cations.

The intrinsic factors governing the diastereofacial selectivity of 2-methyl-5-X-2-adamantyl cations (X = F (I(F)), Si(CH(3))(3) (I(Si))) toward a representative nucleophile, i.e., methanol, have been investigated in the gas phase at 750 Torr and in the 20-80 degrees C temperature range. The kinetic results indicate that CH(3)OH addition to I(F) proceeds through tight transition structures (TS(F)(syn) and TS(F)(anti)) characterized by advanced C-O bonding. The same interactions are much less pronounced in the comparatively loose transition structures involved in the CH(3)OH addition to I(Si) (TS(Si)(syn) and TS(Si)(anti)). The experimental evidence indicates that the activation barriers for the anti addition to I(F) and I(Si) are invariably lower than those for the syn attack. Large adverse entropic factors account for the preferred syn diastereoselectivity observed in the reaction with I(F). Entropy plays a minor role in the much looser transition structures involved in the reaction with I(Si), which instead exhibits a preferred anti diastereoselectivity. Comparison of the above gas-phase results with related theoretical and solution data suggests that the diastereofacial selectivity of I(F) and I(Si) measured in solution arises in part from the differential solvation of the two faces of the pyramidalized ions.

A new virtual reality approach for planning of cardiac interventions.

A novel approach to three-dimensional (3D) visualization of high quality, respiratory compensated cardiac magnetic resonance (MR) data is presented with the purpose of assisting the cardiovascular surgeon and the invasive cardiologist in the pre-operative planning. Developments included: (1) optimization of 3D, MR scan protocols; (2) dedicated segmentation software; (3) optimization of model generation algorithms; (4) interactive, virtual reality visualization. The approach is based on a tool for interactive, real-time visualization of 3D cardiac MR datasets in the form of 3D heart models displayed on virtual reality equipment. This allows the cardiac surgeon and the cardiologist to examine the model as if they were actually holding it in their hands. To secure relevant examination of all details related to cardiac morphology, the model can be re-scaled and the viewpoint can be set to any point inside the heart. Finally, the original, raw MR images can be examined on line as textures in cut-planes through the heart models.

Functional rest through intensive treatment with insulin and potassium channel openers preserves residual beta-cell function and mass in acutely diabetic BB rats.

Diazoxide and the diazoxide-analogue, NNC 55-0118, are potassium channel openers that interfere with insulin secretion from beta-cells. In vitro, we show that these two drugs inhibit insulin release from diabetes-resistant BB rat islets cultured at either low or high glucose concentration and cause an intracellular accumulation of insulin with high glucose. Preservation of beta-cells was investigated in newly diabetic BB rats treated with insulin implants from day 0-8 under oral diazoxide, NNC 55-0118 or solvent gavage once a day from day 0-7. Three of eight rats (37.5%) treated with diazoxide and three of ten (30%) treated with NNC 55-0118 retained near normal C-peptide responses when challenged with glucose/arginine on day 9, whereas none of eight (0%) solvent-treated rats showed a C-peptide response. Immunohistochemical staining for insulin and glucagon showed that all the C-peptide responding rats had insulin-positive cells in their islets. In contrast, islets from non-responding rats displayed marked inflammation or end-stage lesions. Furthermore, rats with C-peptide response and treated with NNC 55-0118 exhibited only minimal signs of islet inflammation, whereas C-peptide responding diazoxide-treated rats had low level islet inflammation. These results imply that it is conceivable to preserve residual beta-cells at diabetes onset by induction of target cell rest with potassium channel openers and continuous insulin treatment.

Functional interplay between p53 and E2F through co-activator p300.

Both E2F and p53 are sequence specific transcription factors that regulate early cell cycle progression. The pathway of control mediated through E2F governs the transition from G1 into S phase whereas p53 in response to genotoxic stress can facilitate cell cycle arrest or apoptosis. The mechanisms which influence the outcome of p53 induction are not clear, although transcription of the p53 target gene, encoding the cdk-inhibitor p21(Waf1/Cip1), correlates with p53-mediated cell cycle arrest. Here using a combination of biochemical and functional assays we identify p300 as a co-activator required for p53-dependent transcriptional activation of Waf1/Cip1. Furthermore, we show that the cdk-inhibitor p21(Waf1/Cip1) autoregulates in a positive fashion transcription through modulating the activity of the p53/p300 complex, whilst negatively regulating the activity of E2F by preventing cdk-dependent phosphorylation of pRb. Consistent with a role for p21(Waf1/Cip1) in the autoregulation of p53-dependent transcription, p300 augments the ability of p53 to cause G1 arrest and, conversely, cells undergoing p53-dependent apoptosis are rescued by p300. Thus, our data suggest that the ability of p300 to interact with p53 influences the physiological consequence of p53 activation. From previous studies it is known that cells expressing aberrant levels of E2F-1 can undergo p53-dependent apoptosis. In addition, we find that E2F-1 can cause apoptosis in p53-/- tumour cells and further p300, which also functions as a co-activator for the E2F/DP heterodimer, enhances the apoptotic activity of E2F-1. In conditions where E2F-1 and p53 co-operate in apoptosis E2F-1 can effectively compete for p300, causing a reduction in p53-dependent transcription. Thus, a functional interaction between p300 and either p53 or E2F-1 has a profound impact on early cell cycle progression, specifically in regulating the contrasting outcomes of cell cycle arrest and apoptosis. These results suggest a critical role for p300 in integrating and co-ordinating the functional interplay between the pathways of growth control mediated by E2F and p53.

Ankle arthroplasty for rheumatoid arthritis and osteoarthritis: prospective long-term study of cemented replacements.

We performed 52 cemented ankle arthroplasties for painful osteoarthritis (OA) (25) or rheumatoid arthritis (RA) (27) using an ankle prosthesis with a near-anatomical design. We assessed the patients radiologically and clinically for up to 14 years using an ankle scoring system. The preoperative median scores were 29 for the OA group and 25 for the RA group and at ten years were 93.5 and 83, respectively. Six ankles in the OA group and five in the RA group required revision or arthrodesis. Survivorship analysis of the two groups showed no significant differences with 72.7% survival for the OA group and 75.5% for the RA group at 14 years.

Orthopedic wound infections. 182 cases after 8913 operations during an 8-year survey.

We performed a surveillance of postoperative wound infections at our department for a period of 8 years. The surveillance was based on forms completed by the surgeons at the department. Retrospectively, by scrutinizing the records of patients with recorded infections, the criteria for infections used by the surgeons were compared with the criteria recommended by the Centers for Disease Control, USA, for routine infection surveillance studies: 1) pus present in the wound, 2) bacteria isolated from the wound, 3) spontaneous wound breakdown or surgical intervention due to suspected infection; if culture is performed, it must be positive, 4) evidence of infection at reoperation or at radiologic or histopathologic examination (restricted to deep infections) or 5) diagnosis of infection by a surgeon. 182 infections were recorded; in 106 (58%) pus was present, drained either spontaneously or by surgical intervention, in 24 (13%) no pus was seen, but the culture was positive. In 116 cases, surgical intervention was performed or wounds spontaneously broke down; pus was found in 101 of these and culture of non-purulent material was positive in 13 and negative in 2. In 52 (29%) patients, only criterion 5 was fulfilled. In surveillance studies where the recordings are based on several observers, the subjective criterion 5 may, as in our study, give a falsely high number of infections, also preventing comparison between studies. We recommend that all suspected infections are cultured and that only criteria 1, 2 and 4 are used.

The predominant E2F complex in human primary haemopoietic cells and in AML blasts contains E2F-4, DP-1 and p130.

The E2F family of transcription factors are thought to play an important role in the control of cell cycle progression. There is now also increasing evidence that some family members may act as oncogenes or tumour suppressor genes. The characterization of these proteins in human primary haemopoietic cells and acute myeloid leukaemia (AML) blasts may thus give an insight to the molecular mechanisms governing proliferation and leukaemogenesis in these cells. Therefore we analysed the expression of E2F-DNA binding activity and the constituent proteins found in the complexes in human primary haemopoietic cells of various lineages. We also studied blasts from 18 patients with acute myeloid leukaemia (AML). On electromobility shift assays (EMSA) a single E2F-DNA binding complex was detected in T cells, B cells and monocytes which was shown to contain E2F-4, DP-1 and p130, indicating that all quiescent haemopoietic cells have the same complex. Examination of 18 AML samples by EMSA revealed the presence of E2F binding and no gross abnormalities were detected. An E2F-4/p130 complex was detected in representative samples of all FAB types analysed. Thus abnormalities of E2F function are unlikely to play a primary pathogenic role in AML.

Functional interaction between DP-1 and p53.

The cellular transcription factor DRTF1/E2F and the tumor suppressor protein p53 play important roles in controlling early cell cycle events. DRTF1/E2F is believed to coordinate and integrate the transcription of cell cycle-regulating genes, for example, those involved in DNA synthesis, with the activity of regulatory proteins, such as the retinoblastoma tumor suppressor gene product (pRb), which modulate its transcriptional activity. In contrast, p53 is thought to monitor the integrity of chromosomal DNA and when appropriate interfere with cell cycle progression, for example, in response to DNA damage. Generic DRTF1/E2F DNA binding activity and transcriptional activation arise when members of two distinct families of proteins, such as DP-1 and E2F-1, interact as DP/E2F heterodimers. In many cell types, DP-1 is a widespread component of DRTF1/E2F DNA binding activity which when expressed at high levels oncogenically transforms embryonic fibroblasts. Here, we document an association between DP-1 and p53 and demonstrate its presence in mammalian cell extracts. In vitro p53 interacts with an immunochemically distinct form of DP-1 and in vivo can regulate transcription driven by the DP-1/E2F-1 heterodimer. At the biochemical level, p53 competes with E2F-1 for DP-1, with a consequent reduction in DNA binding activity. Mutational analysis defines within DP-1 a C-terminal region required for the interaction with p53 and within p53 an N-terminal region distinct from that required to bind to MDM2. Our results establish DRTF1/E2F as a common cellular target in growth control mediated through the activities of pRb and p53 and suggest an alternative mechanism through which p53 may regulate cellular proliferation.

Oxygen transport through methacrylate-based hydrogels with potential biological capability.

The permeability to oxygen of hydrogels prepared from copolymers of 2-hydroxymethyl methacrylate and p-methacryloxyl-oxyacetanilide have been studied by using an oxygen electrode in combination with a permeometer. The transmissibility Dk/L and the permeability Dk (where D, k and L are, respectively, the diffusion coefficient, the Henry constant and the thickness of the hydrogel) are measured by a combination of steady state and transitory state measurements. Both transport coefficients increase with the water content, which in turn depends on the copolymer composition. The values of these quantities tend toward a limiting value for water-saturated hydrogels. The ratio of the characteristic volume for diffusion of the oxygen molecule to the free volume of water per mole water is found to be in the vicinity of 0.10, and this value increases slightly as the fraction of the hydrophilic comonomer in the hydrogel increases. A detailed comparison of the biogels studied with six commercial contact lenses has also been performed.

Stimulation of E2F1/DP1 transcriptional activity by MDM2 oncoprotein.

The MDM2 proto-oncogene is found amplified in a variety of tumours. The oncogenic capacity of the MDM2 protein is attributed to its ability to bind the p53 tumour-suppressor protein and mask its transcriptional activation potential. Here we show that MDM2 makes a functional contact with two cooperating transcription factors, E2F1 and DP1 (refs 4,5), which are involved in S-phase progression. MDM2 contacts the activation domain of E2F1 using residues conserved in the activation domain of p53. However, in contrast to its repression of p53 activity, MDM2 stimulates the activation capacity of E2F1/DP1. These results indicate that MDM2 not only releases a proliferative block by silencing the tumour suppressor p53, it also positively augments proliferation by stimulating the S-phase inducing transcription factors E2F1/DP1.

DP-1: a cell cycle-regulated and phosphorylated component of transcription factor DRTF1/E2F which is functionally important for recognition by pRb and the adenovirus E4 orf 6/7 protein.

The cellular transcription factor DRTF1/E2F integrates cell cycle events with the transcription apparatus through its cyclical interactions with important regulators of cellular proliferation. Two sequence-specific DNA binding proteins, DP-1 and E2F-1, are components of DRTF1/E2F which synergistically interact in a DP-1/E2F-1 heterodimer. Here, we show that DP-1 is a very frequent, possibly universal, component of DRTF1/E2F in 3T3 cells since it is present in all forms of the DNA binding activity that occur during cell cycle progression. Furthermore, the DP-1 polypeptide, which is phosphorylated, undergoes a phosphorylation-dependent mobility shift during the cell cycle suggesting that its level of phosphorylation is regulated during cell cycle progression. A C-terminal region in DP-1 can interact with pRb which, in the context of the DP-1/E2F-1 heterodimer, contributes to the efficiency of pRb binding. The DP-1/E2F-1 heterodimer specifically interacts with the adenovirus type 5 E4 orf 6/7 protein, to produce a DNA binding activity which binds co-operatively to, and transcriptionally activates through, two appropriately positioned E2F sites in a manner which resembles the regulation of DRTF1/E2F by E4 orf 6/7 during adenovirus infection. We conclude that DP-1 is a frequent and cell cycle-regulated component of DRTF1/E2F, and that in the DP-1/E2F-1 heterodimer it is functionally important for recognition by pRb and the E4 orf 6/7 protein.

[Finger tip injuries. A comparative study of silver sulfadiazine and fucidin gauze]. / Pulpalaesioner. En sammenlignende undersøgelse af sølvsulfadiazin og fusidin-gaze.

Eighty-eight superficial finger-tip lesions were randomized after thorough cleaning to either silver sulphadiazine treatment of Fucidin fusidic acid gauze. In the silver sulphadiazine group the wounds were covered with a non-sterile PVC gloce and redressed at least every third day; in the other group Fucidin gauze was applied and a tubigauze dressing was left in situ for ten days, after which a new dressing was applied. All patients were treated until healed and followed for at least six months after injury. Patients in the silver sulphadiazine group required shorter time for healing and shorter sick leave. The treatment is recommended because of the easy procedure and the good results.