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The consideration in Canada of risk analysis for microorganisms in food by the Health Protection Branch (HPB) is in its formative stage. These analyses have become necessary because of the need for better control of imported and domestically produced food. A working group has been established between Health Canada and Agriculture and Agrifood Canada to consider a joint approach to risk analysis for foodborne microbiological hazards. Within the Bureau of Microbial Hazards of the HPB four health-risk determinations have been initiated. Three of these are for broad categories of products: dairy, fish and shellfish, and meat and poultry. These are meant as background documents for more specific risk assessments. The fourth, on cracked eggs, is designed to give management options for the control of this commodity. These determinations are being developed as required and different approaches are being considered. The working group is in agreement that standard definitions of terms and methodologies need to be used, and that these should come from discussions with other national and international agencies and associations, such as the Codex Alimentarius Commission. Recommendations include the need both for risk analysis to provide a clear process for food control by government and industry, and for directed research and surveys to provide more information on the status of hazards at different stages of specific processes from preharvest to consumer handling.

The uptake of radiolabeled fibrinogen in canine thrombi was determined at varying times after thrombus induction by electric current. The greatest thrombus/blood ratio was achieved when fibrinogen was administered 4 hr after thrombus induction but definite thrombus fibrinogen uptake was still observed when the tracer was administered up to 72 hr after thrombus induction. There was continued fibrinogen accumulation despite a decrease in weight of older thrombi suggesting that net thrombus propagation is not necessary for labeled fibrinogen uptake. Our results suggest that the fibrinogen uptake test may be useful for the diagnosis of deep vein thrombosis for several days after the onset of thrombosis.

We have examined radioiodinated fibrinogen prepared at high levels of iodination as an agent for improved in vivo thrombus detection. Fibrinogen containing 25, 50, and 100 atoms of iodine per molecule is prepared by an electrolytic procedure and is compared with conventional radiolabeled fibrinogen (less than 0.5 iodine atom per molecule) prepared by the iodine monochloride method. The level of iodination has little effect on the isotopic clottability of the product, but its degree of aggregation and its rate of blood clearance in experimental animals is strongly dependent on iodination level. Isotopic thrombus: blood ratios obtained in recently induced thrombi with the 25 atom per molecule preparation average about 50:1, twice as high as the ratios obtained with conventionally labeled fibrinogen.

We have investigated the in vivo behavior of 99mTc-fibrinogen, prepared by a mild and efficient electrolytic method employing tin electrodes. The clearance mechanisms of this agent were studied, and its efficacy for imaging deep-vein thrombi in dogs with an Anger camera was determined. The 99mTc-fibrinogen preparations, which are stable in vitro, undergo partial rapid exchange of the technetium with other plasma proteins and with anions of the blood buffer system in vivo, resulting in an early drop in the percent of radioactivity associated with clottable protein. However, very little or no oxidation to pertechnetate occurs. The nonclottable material is much more rapidly cleared from the blood than the remaining 99mTc-fibrinogen, and the proportion of clottable protein activity increases with time. The fraction of 99mTc-fibrinogen that remains intact in vivo is biologically active and will incorporate into thrombi. Higher thrombus-to-blood activity ratios are obtained with 99mTc-fibrinogen than with radioidinated fibrinogen when both agents are injected into dogs 4 hr after induction of femoral vein thrombosis. Clearly delineated images of the thrombi are obtained, beginning about 2.5 hr after injection. Thus, 99mTc-fibrinogen may be of clinical use as a thrombus-imaging agent in patients under-going active thrombosis, especially in regions of high blood pool.

The reliable diagnosis of bacterial endocarditis is an important but difficult clinical problem. The potential ability of technetium-99m-labeled antistaphylococcal antibody to detect infective endocarditis was investigated in a rabbit model. Radiolabeling of the purified antibody was effected by a mild electrolytic procedure, with full retention of immunologic activity. Infective endocarditis was induced in rabbits by placing a catheter through the carotid artery into the left ventricle, followed by i.v. injection of Staphylococcus aureus. The labeled antistaphylococcal antibody was subsequently injected, and its clearance and distribution were studied in the infected rabbits and in normal controls. The ratio of radioactivity on the aortic valve to that in the surrounding heart tissue or blood pool was significantly higher for the infected animals (> 10:1) than for the normals, and should permit visualization of the infection site. This radiolabeled antibody technique may provide a feasible approach to detection of infective endocardial lesions.

Prolyl-2-(1',1'-dimethylallyl)tryptophyldiketopiperazine and 12,13-dehydroprolyl-2-(1',1'-dimethylallyl)tryptophyldiketopiperazine, known metabolites of Aspergillus ustus, were produced in low yield by Penicillium italicum in liquid culture and on unsterilized orange peel.

We have reinvestigated radioiodinated plasminogen as an agent for localizing preformed thrombi. Canine plasminogen was isolated from fresh plasma by the affinity chromatography technique on a lysine-sepharose 4B column and tagged with I-123 or I-131, at less than one iodine atom per molecule of enzyme, by the conventional ICI method. When injected into dogs more than 2 days after thrombus induction, radioiodinated plasminogen produced thrombus-to-blood activity ratios of 7.8 +/- 2.4. Thrombi as old as 6 days can be visualized in 80% of the cases. Both the weight of the thrombus and the thrombus-to-blood ratio are more variable for 1-day-old thrombi; this may be associated with plasminogen release accompanying thrombus retraction. The results suggest that radioiodinated plasminogen has potential as an imaging agent for pre-existing thrombi.

A method for producing protein-iodination-grade 123I suitable for use with a compact bio-medical cyclotron is reported. The preparation of highly iodinated fibrinogen (25 123I atoms per molecule) is described, and its successful use as a thrombus-imaging agent in experimental animals is reported. This new agent clears from the blood faster than conventional radioiodinated fibrinogen and gives higher thrombus-to-blood activity ratios. Thus, the detection of deep-vein thrombi in areas of large blood pool is enhanced, and images can be obtained sooner after administration of the radiopharmaceutical. Induced 4--8-hr-old femoral-vien thrombi in dogs can be well visualized with a scintillation camera as early as 4 hr and as late as 15 hr after administration of 1 mCi of 123I-labeled highly iodinated fibrinogen.

Several methods of damaging red blood cells (RBCs) for splenic imaging were compared to determine the optimum approach. The RBCs from donor animals were labeled with 99mTcO4- and damaged by heat, excess acid citrate dextrose (ACD), excess Sn(II) ion, or the sulfhydryl inhibitors N-ethylmaleimide (NEM) or p-hydroxymercuribenzoate (PMB). The organ distributions of undamaged and damaged RBCs were determined in rats, and splenic imaging studies were performed in rabbits. Splenic deposition and spleen-to-liver ratios with heat- or sulfhydryl-damaged 99mTc-RBCs were significantly greater (p less than 0.001) than the values obtained using ACD or Sn(II) ion. Heat-damaging produces good splenic localization of 99mTc-RBCs but requires rigidly controlled incubation conditions. NEM-damaging provides an excellent and predictable alternative approach.