Blast crisis is the most advanced stage of chronic myelogenous leukemia (CML) and is highly refractory to therapy. CML is caused by expression of the chimeric BCR-ABL tyrosine kinase oncogene, the product of the t(9;22) Philadelphia translocation. Imatinib (Glivec, formerly STI571) is a rationally developed, orally administered inhibitor of the Bcr-Abl tyrosine kinase. A total of 260 patients with CML were enrolled in a phase II trial, of whom 229 had a confirmed diagnosis of CML in blast crisis. Patients were treated with imatinib in daily oral doses of 400 mg or 600 mg. Imatinib induced hematologic responses in 52% of patients and sustained hematologic responses lasting at least 4 weeks in 31% of patients, including complete hematologic responses in 8%. For patients with a sustained response, the estimated median response duration was 10 months. Imatinib induced major cytogenetic responses in 16% of patients, with 7% of the responses being complete. Median survival time was 6.9 months. Nonhematologic adverse reactions were frequent but generally mild or moderate. Episodes of severe cytopenia were also frequent and were attributable to the underlying condition and treatment with imatinib. Drug-related adverse events led to discontinuation of therapy in 5% of patients, most often because of cytopenia, skin disorders, or gastrointestinal reactions. These results demonstrate that imatinib has substantial activity and a favorable safety profile when used as a single agent in patients with CML in blast crisis. Additional clinical studies are warranted to explore the efficacy and feasibility of imatinib used in combination with other antileukemic drugs. (Blood. 2002;99:3530-3539)

To determine environmental risk factors for sporadic E. coli O157 infection in Scotland we undertook a prospective, matched case-control study between 1 October 1996 and 31 March 1999. One hundred and eighty-three cases and 545 matched controls were recruited. Contact with animal faeces (OR = 3.65; 95% CI 1.81, 7.34: P < 0.0005) and likely contact with animal faeces (OR = 4.8; 95% CI 2.42, 9.48; P < 0.0005) emerged as strong risk factors for infection. Certain exposures (mainly food-related) were inversely associated with infection i.e. were statistically protective. Most striking was the consumption of bottled water (OR = 0.28; 95% CI 0.15, 0.52; P < 0.0005). Transmission of E. coli O157 does not occur simply through contaminated food. Members of the public need to be aware of the potential for acquiring E. coli O157 through contamination of the environment with animal faeces so that they may take measures to mitigate their risk.

A group of ten short tandem repeat (STR) loci suitable for PCR typing from DNA of domestic cats is evaluated for genetic individualization using blinded samples of eight putative feline blood specimens. The ten loci were also typed in a 70 member cat pedigree to demonstrate Mendelian inheritance and independent assortment. A "match window" or measurement precision estimate was empirically established by determining the maximum gel migration difference among alleles identical by descent in different individuals of the pedigree. Hardy-Weinberg equilibrium and abundant heterozygosity was observed for each locus in cat population samples from Canada and the USA. The probabilities of two unrelated individuals matching by chance (Pro) at all ten loci was estimated as 1.35 X 10-m. We present a conservative approach to compute, for forensic consideration, the mathematical likelihood of a chance genotypic match between DNA evidence from a crime scene and the suspect composite STR genotypes for species or populations when genotype frequency information is not available.

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