Morphological and biochemical correlates of chemical induced injury in the lung

We have reviewed some of the factors which contribute to lung damage by various toxicants. These include disposition of the chemical, its metabolism, individual cell type susceptibility and the potential for the tissue to repair. We have discussed the use of biochemical parameters to measure the functional activity of individual cell types in order to predict the damage to specific cell types and concluded that careful morphological analysis of lung tissue is likely to provide a more sensitive and informative measure of specific cell type injury. However, in order to investigate the mechanism of toxicity of pulmonary toxicants it is essential to establish the primary biochemical event that leads to cell damage and morphological change. The importance of separating the relevant biochemical change(s) from the cascade of biochemical events associated with dead and dying cells and the reparative response of the lung is emphasised.This report results from a discussion sponsored and organised by the Advisory Subgroup in Toxicology (AST) of the European Science Foundation's Standing Committee for the European Medical Research Councils and held at the Medical Research Council Toxicology Unit, Carshalton, U. K. Those taking part were: W. N. Aldridge (AST; as above); J. Bignon (Unit for Research in Renal and Pulmonary Pathology, University of Paris, Creteil, France); P. H. Burri (Section of Developmental Biology, Institute of Anatomy, University of Berne, Switzerland); G. M. Cohen (as above); D. Dinsdale (MRC Toxicology Unit, Carshalton U. K.); P. Hedqvist (Dept. of Physiology, Karolinska Institute, Stockholm, Sweden); D. Henschler (AST; Dept. of Toxicology and Pharmacology, University of Wurzburg, FDR); G. J. Laurent (Biochemistry Unit, Cardiothoracic Institute, University of London, London, U. K.); R. Lauwerys (AST Industrial and Medical Toxicology Unit, University of Louvain, Brussels, Belgium); F. Lembeck (AST; Dept. for Experimental and Clinical Pharmacology, University of Graz, Austria); N. Lery (AST; Poison Control Centre, Lyon, France); P. Moldeus (Dept. of Forensic Medicine, Karolinska Institute, Stockholm, Sweden); B. Nemery (MRC Toxicology Unit, Carshalton, U. K.); A. Saria (Dept. for Experimental and Clinical Pharmacology, University of Graz, Austria); L. L. Smith (as above);B. Terracini (AST; Dept. of Pathology and Cancer Epidemiology, University of Turin, Italy)     

Stress injury of the distal radial growth plate

We report 21 cases of stress injury of the distal radial growth plate-occurring in gymnasts before skeletal maturity. The injury appears to be caused by inability of the growth plate to withstand rotational and compressive forces. Our observations have confirmed that the skeletal age of gymnasts is retarded, which increases the length of time during which the epiphysis is at risk of damage.     

Left ventricular aneurysm formation: an iatrogenic cause for the third mogul

Two cases of left ventricular pseudoaneurysm formation developing post-operatively after mitral valve replacement are reported. The chest radiographs showed an abnormal protuberance on the left heart border at the site of the "third mogul". The definitive diagnosis of this protuberance, resulting from the development of a left ventricular aneurysm, was made on angiography in each case. This site is unusual for left ventricular aneurysm formation, with the exception of the annular subvalvular aneurysm described in the negro population. Relevant aetiological factors in the development of these post-operative left ventricular pseudoaneurysms are considered. Since pseudoaneurysms are more prone to rupture than true aneurysms, it is concluded that early diagnosis of development of these left ventricular pseudoaneurysms should be made.     

Inhibition of contact sensitivity reactions to DNFB by topical cyclosporin application in the guinea-pig.

Contact sensitivity skin reactions to dinitrofluorobenzene (DNFB) were inhibited by twice daily topical application of cyclosporin (CsA, 2%) in normal guinea-pigs and in those with enhanced contact sensitivity reactions following pre-treatment with cyclophosphamide. In contrast to oral administration of CsA (25 mg/kg) for 4 days, topical application of the drug over the same period did not result in systemic absorption (as measured by radioimmunoassay) or in any evidence of nephrotoxicity.     

Comparison of rapid identification assays for Staphylococcus aureus.

A total of 137 strains of Staphylococcus species were blindly tested by four rapid serological assays, and the results were compared with those of the tube coagulase assay. For the S. aureus isolates, the Sero-STAT Staph assay gave six false-negative results, four of which were for methicillin-resistant strains. The Accu -Staph, Staphylatex , and Staphyloslide assays identified all the coagulase-positive strains as Staphylococcus aureus. Among the coagulase-negative staphylococci, false-positive results were seen with strains of S. capitis. S. saprophyticus, and S. cohnii. The overall accuracy of the kits compared with the tube coagulase test ranged from 95.1 to 100%.     

Molecular identification of a novel deltaproteobacterium as the etiologic agent of epizootic bovine abortion (foothill abortion)

Epizootic bovine abortion (EBA) is endemic in California's coastal range and the foothill regions of the Sierra Nevada, where it has been the primary diagnosed cause of abortion in beef cattle for >50 years. Investigation of these losses has defined a specific fetal syndrome characterized by late-term abortion or birth of weak or dead calves. Although the unusual clinical presentation and unique fetal pathology associated with EBA have been recognized since the 1950s, the identity of the etiologic agent is unknown. In this study, suppression-hybridization PCR was used to identify a fragment of the 16S rRNA gene of a previously undescribed bacterium in thymus tissue derived from affected fetuses. Phylogenetic analysis revealed that this pathogen was a deltaproteobacterium closely related to members of the order Myxococcales. A specific PCR was subsequently developed to detect the presence of this bacterium in DNA extracted from fetal thymuses. Using histopathology as the definitive diagnosis for EBA, this PCR demonstrated 100% specificity and 88% sensitivity. The bacterium was also detected in the argasid tick Ornithodoros coriaceus, which is the recognized vector of EBA. These data imply a close association between this novel agent and the etiology of EBA.     

Detection of reticulo-endothelial blockade with low-dose test agent.

Blood clearance and organ extraction of a low-dose reticulo-endothelial test agent, technetium labelled tin colloid (TTC), was measured in groups of rabbits pretreated with reticulo-endothelial blocking agents. Electron microscopy and ultrastructure analysis confirmed that Kupffer cells extracted TTC. Pretreatment with silica caused reduced Kupffer cell uptake and spillover of TTC into the spleen. Pretreatment with sheep red cells caused reduced Kupffer cell uptake and reduced splenic uptake but anti-fibronectin caused only reduced splenic uptake of TTC. TTC is a suitable agent to detect alteration of reticulo-endothelial function.     

An intercomparison of IMRT delivery techniques: a case study for breast treatment

Intensity-modulated radiotherapy beams can be delivered using a multileaf collimator by one of two methods: either by superposition of a series of multiple-static fields, or by moving the collimators while the beam is on to produce 'dynamically' modulated beams. The leaf trajectories in this dynamic mode are given by a series of linear steps between control points defining each collimator position at known intervals throughout an exposure. The complexity of the resulting modulation is limited in the first case by the number of fields superposed and in the second case by the number of control points defined. Results are presented for an experimental study that investigates the effect of changing both the number of fields for the multiple-static technique, and the number of control points for a dynamic 'close-in' technique. All deliveries studied are clinical intensity-modulated breast fields. The effect of using a universal wedge in conjunction with the multileaf collimator is also studied, together with a comparison of the relative efficiency, time taken and the absolute dosimetric accuracy of the various delivery options. It is shown that all delivery techniques produce equivalent dose distributions when using 15 control points, with 10 control points being sufficient to produce an adequate breast compensator distribution. Except for the case of a four-control-point dynamic delivery, the universal wedge makes no significant difference to the dose distribution. However, it makes the delivery less efficient. The close-in interpreter consistently produces deliveries that are more efficient than the more conventional sliding-window technique and faster than the multiple-static-field technique. Finally the close-in technique is compared to the more 'standard' leaf-sweep technique and shown to be equivalent.