Survival patterns and cancer determinants in families with myotonic dystrophy type 1.

BACKGROUND AND PURPOSE: Research indicates that patients with myotonic dystrophy type 1 (DM1) are at increased risk of cancer and early death. Family data may provide insights given DM1 phenotypic heterogeneity, the broad range of non-muscular manifestations and the usual delays in the diagnosis of DM1. METHOD: Family history data were collected from 397 genetically and/or clinically confirmed DM1 patients (respondents) enrolled in the US or UK myotonic dystrophy registries. Standardized mortality ratios were calculated for DM1 first-degree relatives (parents, siblings and offspring) by their reported DM1 status (affected, unaffected or unknown). For cancer-related analyses, mixed effects logistic regression models were used to evaluate factors associated with cancer development in DM1 families, including familial clustering. RESULTS: A total of 467 deaths and 337 cancers were reported amongst 1737 first-degree DM1 relatives. Mortality risk amongst relatives reported as DM1-unaffected was comparable to that of the general population [standardized mortality ratio (SMR) 0.82, P = 0.06], whilst significantly higher mortality risks were noted in DM1-affected relatives (SMR = 2.47, P < 0.0001) and in those whose DM1 status was unknown (SMR = 1.60, P < 0.0001). In cancer risk analyses, risk was higher amongst families in which the DM1 respondent had cancer (odds ratio 1.95, P = 0.0001). Unknown DM1 status in the siblings (odds ratio 2.59, P = 0.004) was associated with higher cancer risk. CONCLUSION: There is an increased risk of death, and probably cancer, in relatives with DM1 and in those whose DM1 status is unknown. This suggests a need to perform a careful history and physical examination, supplemented by genetic testing, to identify family members at risk for DM1 and who might benefit from disease-specific clinical care and surveillance.

[Relationship between the level of specific antibodies with disease outcome in Cercopithecus aethiops monkeys in experimental Marburg disease]. / O vzaimosviazi urovnia spetsificheskikh antitel s iskhodom zabolevaniiau obez'ian Cerpithecus aethiops pri éksperimental'noi infektsii virus Marburg.

The level of specific antibodies in the blood of Cercopithecus aethiops monkeys with experimental Marburg hemorrhagic fever appreciably affects the incidence of lethal outcomes in immunized animals infected with Marburg virus. This effect manifests starting from the titers as low as just 1:100. The level of humoral immunity with the specific antibody titer of at least 1:100 depends on the method of antigen preparation. Humoral response was higher upon challenge with formalin-inactivated virus isolated from the blood plasma of infected guinea pigs.