Murine malaria: genetic control of resistance to Plasmodium chabaudi.

Strain variation in the level of resistance to malaria was investigated in inbred strains of mice after infection with Plasmodium chabaudi. When infected intraperitoneally with 10(6) P. chabaudi-parasitized erythrocytes, mice of 11 inbred strains could be separated into two groups by using survival time as the criterion; C57BL/6J, C57L/J, DBA/2J, CBA/J, and B10.A/SgSn mice were found to be resistant to P. chabaudi, whereas A/J, DBA/1J, BALB/c, C3H/HeJ, AKR/J, and SJL/J mice were susceptible. An examination of F1 hybrids revealed that resistance was dominant over susceptibility. A segregation analysis of backcross and F2 progeny derived from susceptible A/J and resistant B10.A/SgSn parental mice suggested that host resistance in this strain combination was genetically controlled by a single, dominant, non-H-2-linked gene. Inheritance of resistance was autosomal, but expression of the trait was influenced by the sex of the host, female mice being more resistant than male mice. Phenotypic expression of the resistance gene was apparent within 6 days of infection as a significant difference between resistant and susceptible mice in the level of parasitemia. A preliminary analysis of the mechanism of resistance showed that compared with susceptible A/J mice, resistant B10.A/SgSn hosts had an augmented erythropoietic response during the course of malaria, as well as phenylhydrazine-induced anemia. These results suggest that the ability to replace destroyed erythrocytes quickly and efficiently may determine host survival after infection with P. chabaudi

Canadian 2003 international consensus algorithm for the diagnosis, therapy, and management of hereditary angioedema

C1 inhibitor deficiency (hereditary angioedema [HAE]) is a rare disorder for which there is a lack of consensus concerning diagnosis, therapy, and management, particularly in Canada. European initiatives have driven the approach to managing HAE with 3 C1-INH Deficiency Workshops held every 2 years in Hungary starting in 1999, with the third Workshop having recently been held in May 2003. The European Contact Board has established a European HAE Registry that will hopefully advance our knowledge of this disorder. The Canadian Hereditary Angioedema Society/Societe d'Angioedeme Hereditaire du Canada organized a Canadian International Consensus Conference held in Toronto, Ontario, Canada, on October 24 to 26, 2003, to foster consensus between major European and North American HAE treatment centers. Papers were presented by investigators from Europe and North America, and this consensus algorithm approach was discussed. There is a paucity of double-blind placebo-controlled trials in the treatment of HAE, making levels of evidence to support the algorithm less than optimal. Enclosed is the consensus algorithm approach recommended for the diagnosis, therapy, and management of HAE and agreed to by the authors of this article. This document is only a consensus algorithm approach and requires validation. As such, participants agreed to make this a living 2003 algorithm (ie, a work in progress) and agreed to review its content at future international HAE meetings. The consensus, however, has strength in that it was arrived at by the meeting of patient-care providers along with patient group representatives and individual patients reviewing information available to date and reaching agreement on how to approach the diagnosis, therapy, and management of HAE circa 2003. Hopefully evidence to support approaches to the management of HAE will approach the level of meta-analysis of randomized controlled trials in the near futur