Imatinib mesylate efficacy in 72 previously treated Philadelphia-positive chronic myeloid leukemia patients with and without additional chromosomal changes: single-center results.

Reported here are 72 previously treated Philadelphia chromosome-positive (Ph+) CML patients on imatinib (IM) therapy, with a focus on patients with additional chromosomal aberrations (CAs). At the start of IM treatment, 49 patients exhibited only the Ph chromosome (68%) and 23 patients (32%) had one or more additional CAs. The most frequent additional changes were deletions on the der(9q) (8 of 23), trisomy 8 (3 of 23), and an extra copy of the Ph chromosome (2 of 23). Five patients had a complex karyotype. At the latest follow-up, 49 of the 72 patients (68%) were alive, including 15 of the 23 patients with additional CAs (65%). Median follow-up was 6.6 years; median duration of IM treatment was 4.4 years. In all, 35 of the 49 patients with Ph only (71%) and 10 of the 23 patients with additional CAs (43%) achieved complete cytogenetic response. All patients with deletion on der(9q) achieved complete cytogenetic response. There was no statistically significant difference in the overall survival of patients with additional CAs and patients with Ph as the sole abnormality. Patients in accelerated phase had significantly worse overall survival on IM, regardless of additional CAs. The present results confirm that the majority of previously treated Ph+ CML patients benefit from starting IM therapy, including patients with defined additional changes. In contrast, patients with complex karyotypes have poor prognosis, even with IM.

Quantitative structure-activity relationships for toxicity and genotoxicity of halogenated aliphatic compounds: wing spot test of Drosophila melanogaster.

Halogenated aliphatic compounds were evaluated for toxic and genotoxic effects in the somatic mutation and recombination test employing Drosophila melanogaster. The tested chemicals included chlorinated, brominated and iodinated; mono-, di- and tri-substituted; saturated and unsaturated alkanes: 1,2-dibromoethane, 1-bromo-2-chloroethane, 1-iodopropane, 2,3-dichloropropene, 3-bromo-1-propene, epibromohydrin, 2-iodobutane, 3-chloro-2-methylpropene, 1,2,3-trichloropropane, 1,2-dichloroethane, 1,2-dichlorobutane, 1-chloro-2-methylpropane, 1,3-dichloropropane, 1,2-dichloropropane, 2-chloroethymethylether, 1-bromo-2-methylpropane and 1-chloropentane. N-methyl-N-nitrosourea served as the positive and distilled water as the negative control. The set of chemicals for the toxicological testing was selected by the use of statistical experiment design. Group of unsaturated aliphatic hydrocarbons were generally more toxic than saturated analogues. The genotoxic effect was observed with 14 compounds in the wing spot test, while 3 substances did not show any genotoxicity by using the wing spot test at 50% lethal concentration. The highest number of wing spots was observed in genotoxicity assay with 1-bromo-2-chloroethane, 1,2-dichloroethane, 1,2-dibromoethane and 1-iodopropane. Nucleophilic superdelocalizability calculated by quantum mechanics appears to be a good parameter for prediction of both toxicity and genotoxicity effects of halogenated aliphatic compounds.

The homozygous KCNQ1 gene mutation associated with recessive Romano-Ward syndrome.

In a 7-year-old boy with normal hearing suffering from repeated syncope an extremely prolonged QTc interval (up to 700 ms) was found. The mother was completely asymptomatic and the father had an intermittently borderline QTc interval (maximum 470 ms) but no symptoms. In the proband a mutation analysis of KCNQ1 gene revealed a homozygous 1893insC mutation. The parents were heterozygous for this mutation. There was no consanguineous marriage in the family. The clinical relevance of these findings is that apparently normal individuals may have a latent reduction of repolarizing currents, a "reduced repolarization reserve," because they are carriers of latent ion channel genes mutations.

Occurrence of notched T wave in healthy family members with the long QT interval syndrome.

The notched T wave is considered 1 of the diagnostic signs of long QT interval syndrome (LQTIS). The investigators report observations of notched T waves in noncarrier members of families with LQTIS and compare the exercise-induced dynamic behavior of these complex T-wave patterns in mutation carriers and noncarriers of 3 families with LQTIS.