A Monte-Carlo code for the detailed simulation of electron and light-ion tracks in condensed matter.

In an effort to understand the basic mechanism of the action of charged particles in solid radiation dosimeters, we extend our Monte-Carlo code (MC4) to condensed media (liquids/solids) and present new track-structure calculations for electrons and protons. Modeling the energy dissipation process is based on a model dielectric function, which accounts in a semi-empirical and self-consistent way for condensed-phase effects which are computationally intractable. Importantly, these effects mostly influence track-structure characteristics at the nanometer scale, which is the focus of radiation action models. Since the event-by-event scheme for electron transport is impractical above several kilo-electron volts, a condensed-history random-walk scheme has been implemented to transport the energetic delta rays produced by energetic ions. Based on the above developments, new track-structure calculations are presented for two representative dosimetric materials, namely, liquid water and silicon. Results include radial dose distributions in cylindrical and spherical geometries, as well as, clustering distributions, which, among other things, are important in predicting irreparable damage in biological systems and prompt electric-fields in microelectronics.

Radiation dosimetry using three-dimensional optical random access memories.

The ability to determine particle type and energy plays an important role in the dosimetry of heavy charged particles (HCP) and neutrons. A new approach to radiation dosimetry is presented, which is shown to be capable of particle type and energy discrimination. This method is based on utilising radiation induced changes in the digital information stored on three-dimensional optical random access memories (3D ORAM). 3D ORAM is a small cube (a few mm3) composed of poly(methyl methacrylate) doped with a photochromic dye. and it was originally proposed as a memory device in high speed parallel computers. A Nd:YAG laser system is used to write and read binary information (bits) on the ORAM, which functions as a charged particle detector. Both the read and the write processes use two laser beams that simultaneously strike the material to cause a colour change at their intersection (similar to the darkening of light-sensitive sunglasses when exposed to sunlight.) The laser produces colour changes in the ORAM, which then reverts to the original colour ('bit-flips') at sites where energy is deposited from interaction with incident HCP or neutron-recoil protons. The feasibility of this approach was demonstrated both theoretically and experimentally. Calculations based on track structure theory (TST) predict that when HCP interact with the ORAM material, the local energy deposition is capable of inducing measurable 'bit-flips'. These predictions were recently confirmed experimentally using two types of ORAM systems, one based on spirobenzopyran and the other on anthracene, as the photochromic dyes.

Feasibility of a neutron detector-dosemeter based on single-event upsets in dynamic random-access memories.

The feasibility was investigated of a solid-state neutron detector/dosemeter based on single-event upset (SEU) effects in dynamic random-access memories (DRAMs), commonly used in computer memories. Such a device, which uses a neutron converter material to produce a charged particle capable of causing an upset, would be light-weight, low-power, and could be read simply by polling the memory for bit flips. It would have significant advantages over standard solid-state neutron dosemeters which require off-line processing for track etching and analysis. Previous efforts at developing an SEU neutron detector/dosemeter have suffered from poor response, which can be greatly enhanced by selecting a modern high-density DRAM chip for SEU sensitivity and by using a thin 10B film as a converter. Past attempts to use 10B were not successful because the average alpha particle energy was insufficient to penetrate to the sensitive region of the memory. This can be overcome by removing the surface passivation layer before depositing the 10B film or by implanting 10B directly into the chip. Previous experimental data show a 10(3) increase in neutron sensitivity by chips containing borosilicate glass, which could be used in an SEU detector. The results are presented of simulations showing that the absolute efficiency of an SEU neutron dosemeter can be increased by at least a factor of 1000 over earlier designs.

The postsynaptic spectrin/4.1 membrane protein "accumulation machine".

An important aspect of the function of the membrane-associated cytoskeleton has been suggested to be to trap and retain selected transmembrane proteins at points on the cell surface specified by cell adhesion molecules. In the process, cell adhesion molecules are cross-linked to each other, and so junctional complexes are strengthened. In this short review, we will discuss recent advances in understanding the role of this "accumulation machine" in postsynaptic structures. Function in the brain depends on correct ordering of synaptic intercellular junctions, and in particular the recruitment of receptors and other apparatus of the signalling system to postsynaptic membranes. Spectrin has long been known to be a component of postsynaptic densities, and recent advances in molecular cloning indicate that beta spectrins at PSDs are all "long" C-terminal isoforms characterised by pleckstrin homology domains. Isoforms of protein 4.1 are also present at synapses. All four 4.1 proteins are represented in PSD preparations, but it is 4.1R that is most enriched in PSDs. 4.1R binds to several proteins enriched in PSDs, including the characteristic PSD intermediate filament, alpha-internexin. Both 4.1 and spectrin interact with ionotropic glutamate receptors (AMPA and NMDA receptors, respectively): 4.1 stabilises AMPA receptors on the cell surface. By linking these receptors to the cytoskeletal and cell adhesion molecules that specify glutamatergic synapses, the membrane protein accumulation machine is suggested to direct the formation of postsynaptic signalling complexes.

Properties of the C-terminal domain of 4.1 proteins.

At the C-terminus of all known 4.1 proteins is a sequence domain unique to these proteins, known as the C-terminal domain (CTD). Mammalian CTDs are associated with a growing number of protein-protein interactions, although such activities have yet to be associated with invertebrate CTDs. Mammalian CTDs are generally defined by sequence alignment as encoded by exons 18-21. Comparison of known vertebrate 4.1 proteins with invertebrate (Caenorhabditis elegans and Drosophila melanogaster) 4.1 proteins indicates that mammalian 4.1 exon 19 represents a vertebrate adaptation that extends the sequence of the CTD with a Ser/Thr-rich sequence. The CTD was first described as a 22/24-kDa domain by chymotryptic digestion of erythrocyte 4.1 (4.1R) [Leto, T.L. & Marchesi, V.T. (1984) J. Biol. Chem. 259, 4603-4608]. Here we show that in 4.1R the 22/24-kDa fragment is not stable but rapidly processed to a 15-kDa fragment by chymotrypsin. The 15-kDa fragment is extremely stable, being resistant to overnight digestion in chymotrypsin on ice. Analysis of this fragment indicates that it is derived from residues 709-858 (SwissProt accession no. P48193), and represents the CTD of 4.1R. The fragment behaves as a globular monomer in solution. Secondary-structure predictions indicate that this domain is composed of five or six beta strands with an alpha helix before the most C-terminal of these. Together these data indicate that the CTD probably represents an independent folding structure which has gained function since the divergence of vertebrates from invertebrates.

Radiation dosimetry using three-dimensional optical random access memories.

Three-dimensional optical random access memories (3D ORAMs) are a new generation of high-density data storage devices. Binary information is stored and retrieved via a light induced reversible transformation of an ensemble of bistable photochromic molecules embedded in a polymer matrix. This paper describes the application of 3D ORAM materials to radiation dosimetry. It is shown both theoretically and experimentally, that ionizing radiation in the form of heavy charged particles is capable of changing the information originally stored on the ORAM material. The magnitude and spatial distribution of these changes are used as a measure of the absorbed dose, particle type and energy. The effects of exposure on 3D ORAM materials have been investigated for a variety of particle types and energies, including protons, alpha particles and 12C ions. The exposed materials are observed to fluoresce when exposed to laser light. The intensity and the depth of the fluorescence is dependent on the type and energy of the particle to which the materials were exposed. It is shown that these effects can be modeled using Monte Carlo calculations. The model provides a better understanding of the properties of these materials. which should prove useful for developing systems for charged particle and neutron dosimetry/detector applications.

Three-dimensional optical random access memory materials for use as radiation dosimeters.

This article describes the development of the first three-dimensional optical random access memory (3D-ORAM) material and readout system for monitoring energetic neutrons. Two different photochromic dyes, 5'-chloro-6-nitro-1',3',3'-trimethylspiro-[2H-1-benzopyran-2,2'-in doline] (spirobenzopyran) and anthracene, have been investigated for use in these 3-D ORAM dosimeter materials. These dyes were immobilized in a poly(methyl methacrylate) support, and the resulting dosimeter materials were irradiated with neutrons from a Cf-252 source. Fluorescence measurements from the dosimeter show a dramatic decrease in the overall fluorescence intensity of the 3D-ORAM dosimeter exposed to the Cf-252, relative to a nonirradiated dosimeter. In addition, a two-photon excitation readout system has been developed for determining characteristics of the radiation that are necessary for estimating dose.

Review of arterial vascular ultrasound.

Duplex ultrasound (US) is established as having a major role in the assessment of both extracranial carotid disease and lower limb graft surveillance. It is also of considerable value in the assessment of lower limb ischemia when used in conjunction with clinical and pressure measurements, and in the monitoring of abdominal aneurysms. Its many other arterial applications are of interest but are currently less well defined. The impact of power Doppler, contrast agents, harmonic imaging, and 3-dimensional reconstruction techniques is yet to be fully appreciated.

Review of venous vascular ultrasound.

Duplex ultrasound (US) has become the new gold standard in the assessment of acute deep vein thrombosis. In view of the large number of cases with persistent changes, all cases should be reassessed at 6 months to document the extent of residual disease. The role of duplex US in chronic venous disease is less well established but it is evolving as the single most useful examination and is likely to supplant other noninvasive methods in the near future.

Definition of a sequence unique in beta II spectrin required for its axon-specific interaction with fodaxin (A60).

Spectrin isotypes segregate in neurons and are differentially distributed between axons and somatodendritic compartments. Their functions in those compartments are likely to be mediated by proteins that interact selectively with one or other isotype. Fodaxin (an axon-specific protein previously termed A60) colocalizes in CNS neurons with axonal spectrin and in vitro binds brain spectrin (a mixture of alpha I, beta I, and beta II polypeptides) but not erythrocyte spectrin (alpha I and beta I). Because alpha II and beta II spectrin polypeptides are enriched in axons, we investigated a possible binding of fodaxin to the types of spectrin found in axons. Fodaxin did not bind to isolated brain alpha chains. Bacterially expressed C-terminal segments 18-19 of beta II spectrin bound to fodaxin and inhibited the binding of fodaxin to whole brain spectrin. By contrast, recombinant segments 18-19 of the somatodendritic beta I sigma 2 spectrin showed no interaction with fodaxin. Within beta II, fodaxin binding activity was localized to residues 2,087-2,198, which are unique to beta II and link between the end of segment 18 and the pleckstrin homology domain in segment 19. The divergent regions of sequence in segments 19 of beta II and beta I sigma 2 are candidates to mediate the isotype-specific functions of spectrin. Fodaxin is the first protein to be described that discriminates between the unique regions of beta spectrin isoforms.

The value of ultrasound in the assessment of incompetent perforating veins.

To determine the value of ultrasound in identifying significant perforator disease we assessed 121 perforators in 90 legs of 61 consecutive patients referred for assessment of varicose veins over a 6 month period. Perforators greater than 4mm in diameter demonstrated reflux in approximately 60% of cases, perforators 3-4 mm in diameter demonstrated reflux in approximately 45% and perforators less than 3 mm in diameter demonstrated reflux in approximately 25% of cases. From correlation with previous published data we recommend that all perforators greater than 4 mm in diameter be considered incompetent regardless of whether reflux is demonstrated.

Chaotic phasic pattern as sole ultrasound evidence of extensive post-thrombotic change.

We report three cases of extensive post-thrombotic change confirmed at ascending venography but which did not demonstrate the currently accepted duplex ultrasound criteria for post-thrombotic change. We also document a new ultrasound finding which we describe as a chaotic phasic pattern of deep venous flow which was the only duplex evidence of post-thrombotic change in two of the cases. We suggest that its routine inclusion in duplex ultrasound assessment of the deep veins should be considered.

A comparison of colour duplex ultrasound with venography and varicography in the assessment of varicose veins.

Ninety-three legs in 68 consecutive patients presenting for preoperative assessment of varicose veins were examined by a combination of ascending venography with varicography and also by colour duplex ultrasound. Ninety-one to ninety-two per cent of incompetent sapheno-femoral and sapheno-popliteal communications were demonstrated by ascending venography/varicography and 92-95% by ultrasound. Ascending venography/varicography demonstrated 83-90% of incompetent perforators whilst ultrasound demonstrated only 40-63%. We conclude that ultrasound is an accurate method of assessing primary and recurrent sapheno-femoral and sapheno-popliteal incompetence but is of limited value in assessing perforator incompetence. This is a significant limitation of ultrasound in view of the importance of perforator disease, and it is likely that this technique can only be used in combination with other venographic methods.

Prophylaxis against venous thrombosis after total hip arthroplasty.

Venous thrombosis rates were compared in 200 patients undergoing total hip arthroplasty and randomized to receive either fixed mini-dose warfarin (1 mg daily) or adjusted-dose warfarin to maintain an international normalized prothrombin ratio (INR) of 2.0-4.0. Bilateral lower limb venography was performed between days 11 and 13 inclusive. Fixed mini-dose warfarin was associated with a significantly higher rate of total thrombosis (P less than 0.05). General anaesthesia was associated with a significantly higher rate of thrombosis than spinal anaesthesia (P less than 0.05). Adjusted-dose warfarin was associated with more bleeding complications than mini-dose warfarin although these were not attributable to excessive anticoagulation. A single death from pulmonary embolus occurred in the early postoperative period in a patient receiving adjusted-dose warfarin.

Immunoelectron microscopy of acetylcholine receptors and 43 KD protein after rapid freezing, freeze-substitution, and low-temperature embedding in lowicryl K11M.

To label intracellular determinants of the acetylcholine receptor and associated cytoplasmic proteins while preserving optimal ultrastructure, we developed a post-embedment labeling technique that uses rapid-frozen specimens and freeze-substitution without chemical fixatives. This procedure has been made possible through the use of a low-temperature resin (Lowicryl K11M) that can be polymerized with UV light at -60 degrees C. Rapid-frozen muscle cells were used to evaluate the preservation of structure, and Torpedo electroplaque cells and purified postsynaptic membranes were used to quantitatively evaluate the labeling specificity, efficiency, and resolution of the technique. The labeling efficiency of seven different monoclonal antibodies (MAb) to the acetylcholine receptor varied from 3-13%; there was a correlation between the degree of efficiency and the number of epitopes with which the antibodies reacted. The resolution of the technique was not sufficient to determine whether the anti-acetylcholine receptor MAb were bound to the cytoplasmic or the extracellular surface, but was sufficient to correctly determine the location of the receptor-associated 43 KD protein on the cytoplasmic surface.

Chondrosarcoma presenting as an anterior mediastinal mass.

We describe a chondrosarcoma presenting as an anterior mediastinal mass. The tumour was unusual in that it simulated more commonly occurring mediastinal tumours. There was relatively little destruction of the anterior chest wall and very little calcification within the lesion.

Gallstone dissolution by methyl-tert-butyl ether (MTBE) via percutaneous transhepatic cholecystostomy.

Dissolution of gallbladder stones with MTBE appears to be an effective and safe treatment for patients with symptomatic gallstones who are unfit for surgery. However, the procedure is tedious and the stone recurrence rate is as yet unknown.