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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.

Desferrioxamine-human serum albumin conjugate was prepared at pH 4.7 using a water-soluble carbodiimide and at pH 7.8 using glutaraldehyde. The crude conjugate was purified by dialysis and gel filtration. The efficiency of 67Ga labeling of the purified conjugate was greater than 95%, with good in vitro stability. The specific activity ranged from 5 to 50 microCi/mg. Treatment of the conjugate with urea resulted in a 20--30-fold increase in specific activity, suggesting that a number of chelon groups are unavailable for Ga binding due to non-covalent intramolecular cross-linking.

The rate of deiodination of radioiodinated proteins varies with the method of iodination. To elucidate differences in the iodinated protein labeled by various methods, we have hydrolyzed fibrinogen and several small peptides iodinated by the iodine monochloride, chloramine-T, electrolytic and enzymatic methods. Under conditions of either acidic or basic proteolysis, extensive deiodination occurred and the major product was I-. When a protease of Streptomyces griseus was used, radio-iodinated fibrinogen and other polypeptides were degraded to single iodinated amino acid residues and only a small yield of I-. The iodinated amino acids resulting from proteolysis were separated by ion-exchange chromatography. The iodine monochloride and enzymatic methods yielded largely iodotyrosine with small amounts of other iodinated amino acids. The chloramine-T product spectrum varied with the chloramine-T:protein ratio, whereas the electrolytic method yield was a complex function of the reaction conditions. The different methods of iodination lead to some differences in the site of iodination which correlate with stability of the protein-iodine bond.

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.