Implementation of an image-guided radiation therapy program: Lessons learnt and future challenges

The aim of this paper is to detail the experience obtained in implementing an image-guided radiation therapy program at the Northern Sydney Cancer Centre. This required retrofitting a Varian Clinac 21EX with an on-board imager. The commissioning and quality assurance procedures, organisation of a multidisciplinary image guided radiation therapy group, and the development of clinical protocols for orthogonal kV and cone beam computed tomography implementation are described. Reassessment of the image-guided radiation therapy program has continued as new equipment and software versions were made available in the department.     

水体中克雷伯菌属的分布及其在水源性急性肠道感染中的价值

俄罗斯不同气候地区不同功能水体中克雷伯菌属广泛分布。克雷伯菌属可见于遭受生物、化学污染的集中供水的地表水源,无防护的地下蓄水层,缺乏有效清洁、消毒系统的饮用水。研究表明,水体中的克雷伯菌属具有致病性和毒性,对现代药物和消毒剂(氯、紫外线)具有抗性,很容易穿透进入地下蓄水层。克雷伯菌属细菌有很强的致病性(粘附力、侵袭力、磷酸酯酶、卵磷脂酶、脱氧核糖核酸酶、溶血活性),含有致病性遗传标记cnf-1。克雷伯菌属(100 CFU/dm³)可引起急性肠道感染。在不检测总大肠菌群的情况下,检测水体尤其是饮用水中的克雷伯菌属,可以评估所用水的流行病学危险。     

Proteoglycans in human long-term bone marrow cultures: biochemical and ultrastructural analyses

Proteoglycans within the extracellular matrix of human bone marrow have been implicated in the process of hematopoiesis, but little is known about the structure and composition of these macromolecules in this tissue. Hematopoietically active human long-term bone marrow cultures were incubated with medium containing 35S-sulfate and 3H-glucosamine as labeling precursors. Proteoglycans present in the medium and cell layer were extracted with 4 mol/L guanidine HCI and purified by diethylaminoethyl (DEAE)-Sephacel ion exchange and molecular sieve chromatography. Both culture compartments contain a large chondroitin sulfate proteoglycan (MI, CI) that eluted in the void volume of a Sepharose CL-4B column and contained glycosaminoglycan chains of molecular weight (mol wt) approximately 38,000. A second population of sulfate-labeled material was identified as a broad heterogenous peak (MII, CII) that was included on Sepharose CL-4B at Kav = 0.31. This material when chromatographed on Sepharose CL-6B could be further separated into a void peak (MIIa, CIIa) and an included peak eluting at Kav = 0.39 (MIIb, CIIb). The void peaks (MIIa, CIIa) were susceptible to chondroitinase ABC digestion (99%) but slightly less susceptible to chondroitinase AC digestion (90%). Papain digestion of these peaks revealed them to be proteoglycans with glycosaminoglycan chains of mol wt approximately 38,000. The included peaks on Sepharose CL-6B (MIIb, CIIb) from both medium and cell layer compartments resisted digestion with papain, indicating the presence of glycosaminoglycan chains of mol wt approximately 38,000 either free or attached to a small peptide. Although this material was susceptible to chondroitinase ABC (98%), it was considerably less susceptible to chondrotinase AC (approximately 60%), indicating that it contained dermatan sulfate. A small amount of heparan sulfate proteoglycan was also identified but constituted only approximately 10% of the total sulfated proteoglycan extracted from these cultures. Additionally, approximately 40% of the incorporated 3H- activity radioactivity was present as hyaluronic acid. Electron microscopy revealed a layer of adherent cells covered by a mat containing ruthenium red-positive granules that were connected by thin filaments. The extracellular matrix layer above the adherent cells contained a mixture of hematopoietic cells. Chondroitinase ABC treatment of the cultures completely removed the ruthenium red-positive granules overlying the cells and resulted in a loss of approximately 70% of the 35S-sulfate-labeled material from the cell layer.(ABSTRACT TRUNCATED AT 400 WORDS)     

Relative Bioavailability of Lead from Mining Waste Soil in Rats

The purposes of this study were to determine the extent of absorptionof lead (Pb) in mining waste soil from Butte, Montana, and toinvestigate the effect of mining waste soil dose (g soil/day)on tissue lead concentrations. Young, 7- to 8-week-old maleand female Sprague-Dawley rats (5/sex/group) were given miningwaste soil that contained 810 or 3908 ppm lead mixed in a purifieddiet (AIN-76) at four different dose levels (0.2, 0.5, 2, and5% dietary soil) for 30 consecutive days. Standard groups includeduntreated controls and dosed feed soluble lead acetate groups(1, 10, 25, 100, and 250 µg Pb/g feed). The test soildose levels bracketed a pica child's soil exposure level andthe lead acetate concentrations bracketed the test soil doselevels of lead. Liver, blood, and femur were analyzed for totallead concentration using graphite furnace atomic absorptionspectroscopy. Clinical signs, body weight, food consumption,and liver weights for test soil and standard groups were similarto control. Tissue lead concentrations from test soil animalswere significantly lower than the tissue concentrations forthe lead acetate group. Relative percentage bioavailabilityvalues, based on lead acetate as the standard, were independentof the two different test soils, dose levels, and sex and wereonly slightly dependent on the tissue (blood> bone, liver).Mean relative percentage bioavailability values of lead in theButte mining waste soil were 20% based on the blood data. 9%based on the bone data, and 8% based on the liver data. Theresults of this study will provide the information needed todetermine the significance of lead exposure from Butte soilsin assessing human health risks as part of the Superfund RemedialInvestigation/Feasibility Study process.     

EFFECT OF ANAESTHETIC AGENTS ON BILE FLOW AND BILIARY EXCRETION OF 131I- CHOLYLGLYCYLTYROSINE IN THE RAT

We have compared in the rat the effects of i.v. anaestheticagents on bile flow rate and on the biliary excretion of a novelbile acid, ^131l-cholylglycyltyrosine (¹³¹l-cholylgly.tyr.).Etomidate 1-mg bolus and 2-mg h^–1 infusion, Althesin 3-mgbolus and 14.5-mg h^–1 infusion and propofol 3.3-mg bolusand 3.3-mg h^–1 were given via a tail vein cannula andpentobarbitone 50 mg kg^–1 was given by the intraperitonealroute, to groups of six rats. Each animal received only oneanaesthetic agent. One hour after cannulation of the commonbile duct, ¹³¹l-cholylgly.tyr. 5 µCi was injected intothe jugular vein and bile was collected every 1 min for 10 min.The mean (SD) percentage cumulative biliary excretion of ¹³¹l-cholylgly.tyr.at the end of 10 min was: propofol group 74.1 (5.2)% Althesingroup 82.3 (2.2)%; etomidate group 69.4 (17.6)%; pentobarbitonegroup 76.4 (3.2)%. Propofol and Althesin were relatively morecholeretic, causing bile flow rates twice that produced by pentobarbitone.Only Althesin caused a significant increase in biliary excretionof ¹³¹l-cholylgly.tyr. relative to that in rats that receivedpentobarbitone. Bile flow rates for the respective anaesthetictechniques (µl min^–1/100 g body weight) (mean (SD))were: propofol group 14.1 (1.8); Althesin group 12.5 (1.7);etomidate 8.5 (1.4); pentobarbitone group 7.3 (1.0). There wasa marked metabolic acidosis in all rats except in the propofolgroup, in which normal acid-base status and oxygenation wereobserved. Previously presented at the Medical Research Society and published(abstract form) in Clinical Science and Molecular Medicine 1986;71: 71–72.     

Effects of 1,1-Dichloroethene and of Some of Its Metabolites on the Functional Viability of Mouse Hepatocytes

1,1-Dichloroethene (DCE) is hepatotoxic in rodents, and theexpression of its toxicity involves probably its metabolism.In this study the role of DCE metabolites in the generationof the hepatotoxic lesion was investigated. Hepatocytes frommale BALB/c mice in suspension were used as the experimentalmodel. Cells were incubated with DCE for up to 5 hr and cellularviability was assessed by measurement of the release of lactatedehydrogenase into the medium and by alterations in the reductionof the dye 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazoliumbromide. After incubation for 3 hr DCE at 0.5 mM caused maximaltoxicity, whereas at 0.1 mM DCE was only marginally toxic. Cytotoxicitywas exacerbated by pretreatment of mice with buthionine sulfoximine(1.6 g/kg), an inhibitor of glutathione biosynthesis, given4 hr prior to hepatocyte isolation. Inclusion of N-acetylcysteine(10 mM) into the incubate protected cells against DCE-inducedcytotoxicity. Coincubation with octylamine (0.5 mM), an inhibitorof cytochrome P450, abolished the cytotoxic potential of 0.5mM DCE during incubation for 3 hr. DCE toxicity was increasedin hepatocytes from mice which had received ethanol or acetonein their drinking water, both of which induce levels of thehepatic cytochrome P450 isozyme P450 2E1. Incubation of cellswith the P450 2E1 inhibitors N,N-dimethylformamide (10 mM) ordiethyldithiocarbamate (100 µM) protected liver cellsagainst the detrimental effect of DCE. Pretreatment of animalswith phenobarbital, which induces the P450 2B subfamily, or3-methylcholan-threne, which induces P450 1A1, did not affectthe degree of hepatocytotoxicity elicited by DCE. The DCE metaboliteschloroacetic acid and dichloroacetaldehyde at 0.75 mM were toxictoward the cells; however, their toxic potency was inferiorto that of DCE. Dichloroacetic acid, another product of metabolicDCE oxidation, and S-(chloroacetyl)glutathione and glutathionylacetylglutathione,both of which are generated by conjugation of DCE metaboliteswith glutathione, at concentrations of up to 5 mM did not interferewith hepatocyte viability. The results suggest that (i) DCEundergoes metabolic toxification in mouse hepatocytes, (ii)P450 2E1 is responsible for the metabolic activation of DCE,and (iii) conjugation with glutathione is a detoxification step.