Ghez D.,Institute Gustave Roussy |
Micol J.-B.,Institute Gustave Roussy |
Pasquier F.,Institute Gustave Roussy |
Auger N.,Institute Gustave Roussy |
And 10 more authors.
European Journal of Cancer | Year: 2013
Even in the tyrosine kinase inhibitors era, the prognosis of patients with chronic myeloid leukaemia in myeloid blast crisis remains dismal with few patients surviving longer than 6 months. Here we report the cases of 5 patients treated with the combination of 5-azacytidine and tyrosine kinase inhibitors for myeloid blast crisis CML. All patients achieved a complete haematological response including two with a complete cytogenetic and major molecular response. Two patients underwent an allogeneic stem cell transplantation. One died from relapse 34 months from diagnosis. The second is alive and free from disease at 11 months from diagnosis. The other 3 patients are still in complete haematological response after 15, 24 and 33 months of follow-up. These results suggest that the combination has a significant activity in myeloid blast crisis and may increase survival. © 2013 Elsevier Ltd. All rights reserved. Source
Mignot C.,University Pierre and Marie Curie |
Lambert L.,University of Lorraine |
Pasquier L.,Service de Genetique Clinique |
Bienvenu T.,University of Paris Descartes |
And 24 more authors.
Journal of Medical Genetics | Year: 2015
Background: Homozygous mutations in WWOX were reported in eight individuals of two families with autosomal recessive spinocerebellar ataxia type 12 and in two siblings with infantile epileptic encephalopathy (IEE), including one who deceased prior to DNA sampling. Methods: By combining array comparative genomic hybridisation, targeted Sanger sequencing and next generation sequencing, we identified five further patients from four families with IEE due to biallelic alterations of WWOX. Results: We identified eight deleterious WWOX alleles consisting in four deletions, a four base-pair frameshifting deletion, one missense and two nonsense mutations. Genotype-phenotype correlation emerges from the seven reported families. The phenotype in four patients carrying two predicted null alleles was characterised by (1) little if any psychomotor acquisitions, poor spontaneous motility and absent eye contact from birth, (2) pharmacoresistant epilepsy starting in the 1st weeks of life, (3) possible retinal degeneration, acquired microcephaly and premature death. This contrasted with the less severe autosomal recessive spinocerebellar ataxia type 12 phenotype due to hypomorphic alleles. In line with this correlation, the phenotype in two siblings carrying a null allele and a missense mutation was intermediate. Conclusions: Our results obtained by a combination of different molecular techniques undoubtedly incriminate WWOX as a gene for recessive IEE and illustrate the usefulness of high throughput data mining for the identification of genes for rare autosomal recessive disorders. The structure of the WWOX locus encompassing the FRA16D fragile site might explain why constitutive deletions are recurrently reported in genetic databases, suggesting that WWOX-related encephalopathies, although likely rare, may not be exceptional. Source
Brochard S.,Center Hospitalo University Morvan |
Brochard S.,French Institute of Health and Medical Research |
Blajan V.,Center Hospitalo University Morvan |
Lempereur M.,Center Hospitalo University Morvan |
And 8 more authors.
European Journal of Paediatric Neurology | Year: 2011
Aims: To determine technical and clinical factors associated with pain when using an analgesic protocol with 50% nitrous oxide/oxygen and anesthetic cream (lidocaine and prilocaine, Emla®) for children with cerebral palsy undergoing botulinum toxin injections. Methods: Monocentric prospective study including 50 children newly injected with a mean age of 6.6 years (±4.32, range 1-18) and 199 injected muscles. Pain was evaluated using the Children's Hospital of Eastern Ontario Pain Scale (CHEOPS). The following variables were noted: gender, age, weight, Gross Motor Function Classification System, type of cerebral palsy (hemiplegic, diplegic, tetraplegic), muscles injected and severe cognitive impairment. The procedure was broken down into three phases for the purpose of pain evaluation: puncture, muscle localization using electrostimulation and injection of botulinum toxin. Results: The mean CHEOPS score was 8.16 (±3.5) and 38% of scores were above the therapeutic threshold of 9. The injection phase was significantly more painful (6.77 ± 3.30) than the puncture (4.88 ± 2.03) and localization (5.46 ± 2.68) phases. The adductor muscles were less painful than other muscles. Children with more severe cognitive impairment seemed to perceive higher levels of pain than the others. Other clinical factors were not associated with pain score. Conclusion: Clinical characteristics seem not strongly correlated to the success or failure of the 50% nitrous oxide/oxygen-Emla® protocol and this pain treatment protocol does not prevent equally all phases of botulinum toxin injections. Future research on the products and its dilution might help to reduce pain level. © 2011 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved. Source