47 results on '"Waghorn K"'
Search Results
2. Detection of leukemia-associated mutations in peripheral blood DNA of hematologically normal elderly individuals
- Author
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Score, J, Chase, A, Forsberg, L A, Feng, L, Waghorn, K, Jones, A V, Rasi, C, Linch, D C, Dumanski, J P, Gale, R E, and Cross, N C P
- Published
- 2015
- Full Text
- View/download PDF
3. Detection and molecular monitoring of FIP1L1-PDGFRA-positive disease by analysis of patient-specific genomic DNA fusion junctions
- Author
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Score, J, Walz, C, Jovanovic, J V, Jones, A V, Waghorn, K, Hidalgo-Curtis, C, Lin, F, Grimwade, D, Grand, F, Reiter, A, and Cross, N C P
- Published
- 2009
- Full Text
- View/download PDF
4. The severity of FIP1L1–PDGFRA-positive chronic eosinophilic leukaemia is associated with polymorphic variation at the IL5RA locus
- Author
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Burgstaller, S, Kreil, S, Waghorn, K, Metzgeroth, G, Preudhomme, C, Zoi, K, White, H, Cilloni, D, Zoi, C, Brito-Babapulle, F, Walz, C, Reiter, A, and Cross, N C P
- Published
- 2007
- Full Text
- View/download PDF
5. Identification of a novel imatinib responsive KIF5B-PDGFRA fusion gene following screening for PDGFRA overexpression in patients with hypereosinophilia
- Author
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Score, J, Curtis, C, Waghorn, K, Stalder, M, Jotterand, M, Grand, F H, and Cross, N C P
- Published
- 2006
- Full Text
- View/download PDF
6. The t(4;9)(q11;q33) fuses CEP110 to KIT in a case of acute myeloid leukemia
- Author
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Grand, F H, Waghorn, K, Ernst, T, Ohyashiki, K, and Cross, N CP
- Published
- 2011
- Full Text
- View/download PDF
7. Clinical evidence for a graft-versus-tumour effect following allogeneic HSCT for t(8;13) atypical myeloproliferative disorder
- Author
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Townsend, W, Cross, N C P, Waghorn, K, Somana, K, Ramsay, A, Thomson, K, and Peggs, K
- Published
- 2009
- Full Text
- View/download PDF
8. Inactivating mutations of the histone methyltransferase EZH2 in myeloid disorders: V420
- Author
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Ernst, T., Chase, A., Score, J., Hidalgo-Curtis, C., Bryant, C., Jones, A., Waghorn, K., Zoi, K., Ross, F., Reiter, A., Hochhaus, A., Drexler, H., Duncombe, A., Cervantes, F., Oscier, D., Boultwood, J., Grand, F., and Cross, N.
- Published
- 2010
9. A novel ETV6-PDGFRB fusion transcript missed by standard screening in a patient with an imatinib responsive chronic myeloproliferative disease
- Author
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Curtis, C E, Grand, F H, Waghorn, K, Sahoo, T P, George, J, and Cross, N C P
- Published
- 2007
- Full Text
- View/download PDF
10. Geological Controls on Fluid Flow and Gas Hydrate Pingo Development on the Barents Sea Margin
- Author
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Waage, M., primary, Portnov, A., additional, Serov, P., additional, Bünz, S., additional, Waghorn, K. A., additional, Vadakkepuliyambatta, S., additional, Mienert, J., additional, and Andreassen, K., additional
- Published
- 2019
- Full Text
- View/download PDF
11. Inactivating mutations of the histone methyltransferase EZH2 in myeloid disorders
- Author
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Ernst, T, Chase, A, Score, J, Hidalgo-Curtis, C, Bryant, C, Jones, A, Waghorn, K, Zoi, K, Ross, F, Reiter, A, Hochhaus, A, Drexler, H, Duncombe, A, Cervantes, F, Oscier, D, Boultwood, J, Grand, F, and Cross, N
- Published
- 2016
12. Letter to the editor. Detection of leukemia-associated mutations in peripheral blood DNA of hematologically normal elderly individuals
- Author
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Score, J, Chase, A, Forsberg, L.A., Feng, L., Waghorn, K., Jones, A.V., Rasi, C., Linch, D.C., Dumanski, J.P., Gale, R.E., and Cross, N.C.P.
- Published
- 2015
13. Genetic variation at MECOM, TERT, JAK2 and HBS1L-MYB predisposes to myeloproliferative neoplasms
- Author
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Tapper, W., Jones, A.V., Kralovics, R., Harutyunyan, A.S., Zoi, K., Leung, W., Godfrey, A.L., Guglielmelli, P., Callaway, A., Ward, D., Aranaz, P., White, H.E., Waghorn, K., Lin, F., Chase, A.J., Baxter, E., Maclean, C., Nangalia, J., Chen, E., Evans, P., Short, M., Jack, A., Wallis, L., Oscier, D., Duncombe, A.S., Schuh, A., Mead, A.J., Griffiths, M., Ewing, J., Gale, R.E., Schnittger, S., Haferlach, T., Stegelmann, F., Döhner, K., Grallert, H., Strauch, K., Tanaka, T., Bandinelli, S., Giannopoulos, A., Pieri, L., Mannarelli, C., Gisslinger, H., Barosi, G., Cazzola, M., Reiter, A., Harrison, C.N., Campbell, P.J., Green, A.R., Vannucchi, A.M., and Cross, N.C.P.
- Subjects
Adult ,Male ,Genotype ,Genes, myb ,Polymorphism, Single Nucleotide ,Article ,Cohort Studies ,Gene Frequency ,GTP-Binding Proteins ,hemic and lymphatic diseases ,Proto-Oncogenes ,Humans ,Genetic Predisposition to Disease ,HSP70 Heat-Shock Proteins ,Polycythemia Vera ,Telomerase ,Alleles ,Aged ,Myeloproliferative Disorders ,Genetic Variation ,food and beverages ,Janus Kinase 2 ,Middle Aged ,Biochemistry, Genetics and Molecular Biology (all) ,Chemistry (all) ,Physics and Astronomy (all) ,MECOM ,TERT ,JAK2 ,HBS1L-MYB ,myeloproliferative ,Peptide Elongation Factors ,MDS1 and EVI1 Complex Locus Protein ,DNA-Binding Proteins ,Case-Control Studies ,Mutation ,Female ,Calreticulin ,Receptors, Thrombopoietin ,Thrombocythemia, Essential ,Transcription Factors - Abstract
Clonal proliferation in myeloproliferative neoplasms (MPN) is driven by somatic mutations in JAK2, CALR or MPL, but the contribution of inherited factors is poorly characterized. Using a three-stage genome-wide association study of 3,437 MPN cases and 10,083 controls, we identify two SNPs with genome-wide significance in JAK2V617F-negative MPN: rs12339666 (JAK2; meta-analysis P=1.27 × 10−10) and rs2201862 (MECOM; meta-analysis P=1.96 × 10−9). Two additional SNPs, rs2736100 (TERT) and rs9376092 (HBS1L/MYB), achieve genome-wide significance when including JAK2V617F-positive cases. rs9376092 has a stronger effect in JAK2V617F-negative cases with CALR and/or MPL mutations (Breslow–Day P=4.5 × 10−7), whereas in JAK2V617F-positive cases rs9376092 associates with essential thrombocythemia (ET) rather than polycythemia vera (allelic χ2 P=7.3 × 10−7). Reduced MYB expression, previously linked to development of an ET-like disease in model systems, associates with rs9376092 in normal myeloid cells. These findings demonstrate that multiple germline variants predispose to MPN and link constitutional differences in MYB expression to disease phenotype., Somatic mutations drive the clonal proliferation of myeloproliferative neoplasms. Here the authors conduct a genome-wide association study and identify germline variation at multiple loci associated with the development and disease phenotype of these cancers.
- Published
- 2015
14. CHRIMP - Chatham Rise (Methane) Pockmarks
- Author
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Bialas, Jörg, Sarkar, Sudipta, Klaucke, Ingo, Pecher, I., Waghorn, K., Hoffmann, Jasper, Schneider von Deimling, Jens, Dannowski, Anke, Erogluer, Nur, Eckardt, Thomas, Davy, B., Coffin, R., Rose, P., Papenberg, Cord, and Koch, Stephanie
- Published
- 2015
15. CHRIMP - 3D seismic analysis of a large seafloor depression on the Chatham Rise, New Zealand
- Author
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Waghorn, K., Pecher, I., Strachan, L., Crutchley, Gareth, Bialas, Jörg, Sarkar, Sudipta, Davy, B., Papenberg, Cord, Koch, Stephanie, Eckardt, Thomas, Kröger, K., Rose, P., and Coffin, R.
- Published
- 2015
16. Detection of leukemia-associated mutations in peripheral blood DNA of hematologically normal elderly individuals
- Author
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Score, J., Chase, A., Forsberg, Lars, Feng, L., Waghorn, K., Jones, A. V., Rasi, Chiara, Linch, D. C., Dumanski, Jan, Gale, R. E., Cross, N. C. P., Score, J., Chase, A., Forsberg, Lars, Feng, L., Waghorn, K., Jones, A. V., Rasi, Chiara, Linch, D. C., Dumanski, Jan, Gale, R. E., and Cross, N. C. P.
- Published
- 2015
- Full Text
- View/download PDF
17. INACTIVATING MUTATIONS OF THE HISTONE METHYLTRANSFERASE EZH2 ARE ASSOCIATED WITH CHROMOSOME 7 ABNORMALITIES IN MYELOID DISORDERS
- Author
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Ernst, T, Chase, A, Score, J, Hidalgo-Curtis, C, Bryant, C, Jones, A, Waghorn, K, Zoi, K, Ross, F, Reiter, A, Hochhaus, A, Drexler, H, Duncombe, A, Cervantes, F, Oscier, D, Boultwood, J, Grand, F, and Cross, N
- Published
- 2010
18. 3-D Images of a Large Pockmark from the Chatham Rise, New Zealand
- Author
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Pecher, I., primary, Waghorn, K., additional, and Bialas, J., additional
- Published
- 2013
- Full Text
- View/download PDF
19. Investigating a Potential Link between Seafloor Pockmarks, Gas Hydrates and Offshore Hydrocarbon Reservoirs in the Canterbury Basin, New Zealand
- Author
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Hillman, J., primary, Gorman, A.R., additional, Pecher, I., additional, Bialas, J., additional, and Waghorn, K., additional
- Published
- 2013
- Full Text
- View/download PDF
20. Transcription factor mutations in myelodysplastic/myeloproliferative neoplasms
- Author
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Ernst, T., primary, Chase, A., additional, Zoi, K., additional, Waghorn, K., additional, Hidalgo-Curtis, C., additional, Score, J., additional, Jones, A., additional, Grand, F., additional, Reiter, A., additional, Hochhaus, A., additional, and Cross, N. C. P., additional
- Published
- 2010
- Full Text
- View/download PDF
21. Detection and molecular monitoring of FIP1L1-PDGFRA-positive disease by analysis of patient-specific genomic DNA fusion junctions
- Author
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Score, J, primary, Walz, C, additional, Jovanovic, J V, additional, Jones, A V, additional, Waghorn, K, additional, Hidalgo-Curtis, C, additional, Lin, F, additional, Grimwade, D, additional, Grand, F, additional, Reiter, A, additional, and Cross, N C P, additional
- Published
- 2008
- Full Text
- View/download PDF
22. Continuity of nursing care and its link to cesarean birth rate.
- Author
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Gagnon AJ, Meier KM, and Waghorn K
- Published
- 2007
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23. A randomized trial of a program of early postpartum discharge with nurse visitation.
- Author
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Gagnon, A J, Edgar, L, Kramer, M S, Papageorgiou, A, Waghorn, K, and Klein, M C
- Subjects
CLINICAL trials ,COMMUNITY health nursing ,COMPARATIVE studies ,HOME care services ,RESEARCH methodology ,MEDICAL cooperation ,PUERPERIUM ,RESEARCH ,TIME ,EVALUATION research ,RANDOMIZED controlled trials ,DISCHARGE planning - Abstract
Objective: Our purpose was to compare an early postpartum discharge program versus standard postpartum care.Study Design: A randomized controlled trial in a 637-bed university hospital included 175 healthy women recruited at 32 to 38 weeks gestation from physicians' offices and sonograms. Experimental intervention consisted of discharge 6 to 36 hours post partum with nursing care available by telephone or at home at 34 to 38 weeks' gestation and at < or = 48 hours and at 3, 5, and 10 days post partum. The control included a postpartum stay of 48 to 72 hours and standard follow-up.Results: At 1 month no significant differences were seen in perceived maternal competence (Experimental-Control = 4.3 points [95% confidence interval-7.7 to 16.3]), infant weight gain (1.2 gm/ day [-2.8 to 5.2]); identification of significant neonatal hyperbilirubinemia (rate ratio 0.50 [0.10 to 2.51]), infant utilization of health services (rate ratio 0.88 [0.45 to 1.73]), or predominant breast-feeding (adjusted odds ratio 1.25 [0.88 to 1.75]). Program participants did have significantly less frequent infant bilirubin testing (rate ratio 0.39 [0.17 to 0.94]). The program also enhanced perceived maternal competence in recent immigrants (26.9 points [2.7 to 51.5]).Conclusions: Early postpartum discharge coupled with prenatal, postnatal, and home contacts leads to no apparent disadvantage and may yield benefits for some mothers and infants. [ABSTRACT FROM AUTHOR]- Published
- 1997
- Full Text
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24. A randomized trial of one-to-one nurse support of women in labor... including commentary by Hodnett E.
- Author
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Gagnon AJ, Waghorn K, and Covell C
- Published
- 1997
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25. Supportive care by maternity nurses: a work sampling study in an intrapartum unit.
- Author
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Gagnon AJ and Waghorn K
- Published
- 1996
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26. Does episiotomy prevent perineal trauma and pelvic floor relaxation?
- Author
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Michael Klein, Gauthier, R. J., Jorgensen, S. H., Robbins, J. M., Kaczorowski, J., Johnson, B., Corriveau, M., Westreich, R., Waghorn, K., and Gelfand, M. M.
27. Low-dose imatinib mesylate leads to rapid induction of major molecular responses and achievement of complete molecular remission in FIP1L1-PDGFRA-positive chronic eosinophilic leukemia
- Author
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Finella Brito-Babapulle, Christoph Walz, Giuseppe Saglio, Rüdiger Hehlmann, Emanuela Ottaviani, Ellen Solomon, Andreas Hochhaus, Catherine Roche-Lestienne, Joannah Score, David Grimwade, Enrico Gottardi, Michela Rondoni, Andreas Reiter, Jelena V. Jovanovic, Katherine Waghorn, Jane F. Apperley, Nicholas C.P. Cross, Claude Preudhomme, Georgia Metzgeroth, Giovanni Martinelli, Helena Popp, Daniela Cilloni, Philipp Erben, Jovanovic JV, Score J, Waghorn K, Cilloni D, Gottardi E, Metzgeroth G, Erben P, Popp H, Walz C, Hochhaus A, Roche-Lestienne C, Preudhomme C, Solomon E, Apperley J, Rondoni M, Ottaviani E, Martinelli G, Brito-Babapulle F, Saglio G, Hehlmann R, Cross NC, Reiter A, and Grimwade D.
- Subjects
Oncology ,medicine.medical_specialty ,Receptor, Platelet-Derived Growth Factor alpha ,Time Factors ,Immunology ,Hypereosinophilia ,Antineoplastic Agents ,Biochemistry ,Polymerase Chain Reaction ,Piperazines ,Fusion gene ,Internal medicine ,hemic and lymphatic diseases ,Hypereosinophilic Syndrome ,Medicine ,Humans ,FIP1L1-PDGFRA ,Molecular lesion ,DNA Primers ,mRNA Cleavage and Polyadenylation Factors ,Chronic eosinophilic leukemia ,Hematology ,business.industry ,Remission Induction ,Imatinib ,Cell Biology ,Exons ,medicine.disease ,United Kingdom ,Kinetics ,Imatinib mesylate ,Pyrimidines ,Treatment Outcome ,Fusion transcript ,CHRONIC EOSINOPHILIC LEUKEMIA ,Benzamides ,Chronic Disease ,Imatinib Mesylate ,medicine.symptom ,business ,medicine.drug - Abstract
The FIP1L1-PDGFRA fusion gene is a recurrent molecular lesion in eosinophilia-associated myeloproliferative disorders, predicting a favorable response to imatinib mesylate. To investigate its prevalence, 376 patients with persistent unexplained hypereosinophilia were screened by the United Kingdom reference laboratory, revealing 40 positive cases (11%). To determine response kinetics following imatinib, real-time quantitative–polymerase chain reaction (RQ-PCR) assays were developed and evaluated in samples accrued from across the European LeukemiaNet. The FIP1L1-PDGFRA fusion transcript was detected at a sensitivity of 1 in 105 in serial dilution of the EOL-1 cell line. Normalized FIP1L1-PDGFRA transcript levels in patient samples prior to imatinib varied by almost 3 logs. Serial monitoring was undertaken in patients with a high level of FIP1L1-PDGFRA expression prior to initiation of imatinib (100 mg/d-400 mg/d). Overall, 11 of 11 evaluable patients achieved at least a 3-log reduction in FIP1L1-PDGFRA fusion transcripts relative to the pretreatment level within 12 months, with achievement of molecular remission in 9 of 11 (assay sensitivities 1 in 103-105). In 2 patients, withdrawal of imatinib was followed by a rapid rise in FIP1L1-PDGFRA transcript levels. Overall, these data are consistent with the exquisite sensitivity of the FIP1L1-PDGFRα fusion to imatinib, as compared with BCR-ABL, and underline the importance of RQ-PCR monitoring to guide management using molecularly targeted therapies.
- Published
- 2007
28. Mutational mechanisms of EZH2 inactivation in myeloid neoplasms.
- Author
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Chase A, Score J, Lin F, Bryant C, Waghorn K, Yapp S, Carreno-Tarragona G, Aranaz P, Villasante A, Ernst T, and Cross NCP
- Subjects
- Animals, Cell Line, Histones genetics, Humans, Lysine genetics, Mice, Enhancer of Zeste Homolog 2 Protein genetics, Mutation genetics, Myeloproliferative Disorders genetics
- Abstract
EZH2, a component of the polycomb repressive complex 2, catalyses the trimethylation of histone H3 lysine 27, a chromatin mark associated with transcriptional repression. EZH2 loss-of-function mutations are seen in myeloid neoplasms and are associated with an adverse prognosis. Missense mutations in the SET/CXC domain abrogate catalytic activity as assessed by in vitro histone methylation assays, but missense mutations clustering in the conserved DI and DII regions retain activity. To understand the role of DI and DII mutations, we initially developed a cell-based histone methylation assay to test activity in a cellular context. Murine induced pluripotent stem cells lacking EZH2 were transiently transfected with wild type or mutant EZH2 (n = 15) and any resulting histone methylation was measured by flow cytometry. All DI mutations (n = 5) resulted in complete or partial loss of methylation activity whilst 5/6 DII mutations retained activity. Next, we assessed the possibility of splicing abnormalities induced by exon 8 mutations (encoding DII) using RT-PCR from primary patient samples and mini-gene assays. Exon 8 mutations resulted in skipping of exon 8 and an out-of-frame transcript. We have therefore shown that mutations within regions encoding EZH2 domains DI and DII are pathogenic by loss of function and exon skipping, respectively.
- Published
- 2020
- Full Text
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29. Molecular response to imatinib in KIT F522C-mutated systemic mastocytosis.
- Author
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Broderick V, Waghorn K, Langabeer SE, Jeffers M, Cross NCP, and Hayden PJ
- Subjects
- Aged, Female, Humans, Mastocytosis, Systemic genetics, Prognosis, Imatinib Mesylate therapeutic use, Mastocytosis, Systemic drug therapy, Mastocytosis, Systemic pathology, Mutation, Protein Kinase Inhibitors therapeutic use, Proto-Oncogene Proteins c-kit genetics
- Published
- 2019
- Full Text
- View/download PDF
30. Ruxolitinib, a potent JAK1/JAK2 inhibitor, induces temporary reductions in the allelic burden of concurrent CSF3R mutations in chronic neutrophilic leukemia.
- Author
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Gunawan AS, McLornan DP, Wilkins B, Waghorn K, Hoade Y, Cross NCP, and Harrison CN
- Subjects
- Biopsy, Blood Cell Count, Bone Marrow pathology, DNA Mutational Analysis, Female, Gene Dosage, Humans, Janus Kinase 1 antagonists & inhibitors, Janus Kinase 2 antagonists & inhibitors, Leukemia, Neutrophilic, Chronic pathology, Middle Aged, Nitriles, Protein Kinase Inhibitors pharmacology, Pyrazoles pharmacology, Pyrimidines, Treatment Outcome, Alleles, Leukemia, Neutrophilic, Chronic drug therapy, Leukemia, Neutrophilic, Chronic genetics, Mutation, Protein Kinase Inhibitors therapeutic use, Pyrazoles therapeutic use, Receptors, Colony-Stimulating Factor genetics
- Published
- 2017
- Full Text
- View/download PDF
31. Genetic variation at MECOM, TERT, JAK2 and HBS1L-MYB predisposes to myeloproliferative neoplasms.
- Author
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Tapper W, Jones AV, Kralovics R, Harutyunyan AS, Zoi K, Leung W, Godfrey AL, Guglielmelli P, Callaway A, Ward D, Aranaz P, White HE, Waghorn K, Lin F, Chase A, Baxter EJ, Maclean C, Nangalia J, Chen E, Evans P, Short M, Jack A, Wallis L, Oscier D, Duncombe AS, Schuh A, Mead AJ, Griffiths M, Ewing J, Gale RE, Schnittger S, Haferlach T, Stegelmann F, Döhner K, Grallert H, Strauch K, Tanaka T, Bandinelli S, Giannopoulos A, Pieri L, Mannarelli C, Gisslinger H, Barosi G, Cazzola M, Reiter A, Harrison C, Campbell P, Green AR, Vannucchi A, and Cross NC
- Subjects
- Adult, Aged, Alleles, Calreticulin genetics, Case-Control Studies, Cohort Studies, DNA-Binding Proteins genetics, Female, GTP-Binding Proteins genetics, Gene Frequency, Genes, myb genetics, Genetic Predisposition to Disease, Genetic Variation, Genotype, HSP70 Heat-Shock Proteins genetics, Humans, Janus Kinase 2 genetics, MDS1 and EVI1 Complex Locus Protein, Male, Middle Aged, Mutation, Myeloproliferative Disorders genetics, Peptide Elongation Factors genetics, Polymorphism, Single Nucleotide, Proto-Oncogenes genetics, Receptors, Thrombopoietin genetics, Telomerase genetics, Transcription Factors genetics, Polycythemia Vera genetics, Thrombocythemia, Essential genetics
- Abstract
Clonal proliferation in myeloproliferative neoplasms (MPN) is driven by somatic mutations in JAK2, CALR or MPL, but the contribution of inherited factors is poorly characterized. Using a three-stage genome-wide association study of 3,437 MPN cases and 10,083 controls, we identify two SNPs with genome-wide significance in JAK2(V617F)-negative MPN: rs12339666 (JAK2; meta-analysis P=1.27 × 10(-10)) and rs2201862 (MECOM; meta-analysis P=1.96 × 10(-9)). Two additional SNPs, rs2736100 (TERT) and rs9376092 (HBS1L/MYB), achieve genome-wide significance when including JAK2(V617F)-positive cases. rs9376092 has a stronger effect in JAK2(V617F)-negative cases with CALR and/or MPL mutations (Breslow-Day P=4.5 × 10(-7)), whereas in JAK2(V617F)-positive cases rs9376092 associates with essential thrombocythemia (ET) rather than polycythemia vera (allelic χ(2) P=7.3 × 10(-7)). Reduced MYB expression, previously linked to development of an ET-like disease in model systems, associates with rs9376092 in normal myeloid cells. These findings demonstrate that multiple germline variants predispose to MPN and link constitutional differences in MYB expression to disease phenotype.
- Published
- 2015
- Full Text
- View/download PDF
32. Limited duration of complete remission on ruxolitinib in myeloid neoplasms with PCM1-JAK2 and BCR-JAK2 fusion genes.
- Author
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Schwaab J, Knut M, Haferlach C, Metzgeroth G, Horny HP, Chase A, Tapper W, Score J, Waghorn K, Naumann N, Jawhar M, Fabarius A, Hofmann WK, Cross NC, and Reiter A
- Subjects
- Amino Acid Sequence, Base Sequence, DNA Mutational Analysis, Humans, In Situ Hybridization, Fluorescence, Janus Kinases antagonists & inhibitors, Male, Molecular Sequence Data, Neoplasm Recurrence, Local, Nitriles, Protein Kinase Inhibitors therapeutic use, Proto-Oncogene Proteins c-bcr genetics, Pyrimidines, Remission Induction, Time Factors, Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy, Leukemia, Myelogenous, Chronic, BCR-ABL Positive genetics, Oncogene Proteins, Fusion genetics, Pyrazoles therapeutic use
- Abstract
Rearrangements of chromosome band 9p24 are known to be associated with JAK2 fusion genes, e.g., t(8;9)(p22;p24) with a PCM1-JAK2 and t(9;22)(p24;q11) with a BCR-JAK2 fusion gene, respectively. In association with myeloid neoplasms, the clinical course is aggressive, and in absence of effective conventional treatment options, long-term remission is usually only observed after allogeneic stem cell transplantation (ASCT). With the discovery of inhibitors of the JAK2 tyrosine kinase and based on encouraging in vitro and in vivo data, we treated two male patients with myeloid neoplasms and a PCM1-JAK2 or a BCR-JAK2 fusion gene, respectively, with the JAK1/JAK2 inhibitor ruxolitinib. After 12 months of treatment, both patients achieved a complete clinical, hematologic, and cytogenetic response. Non-hematologic toxicity was only grade 1 while no hematologic toxicity was observed. However, remission in both patients was only short-term, with relapse occurring after 18 and 24 months, respectively, making ASCT indispensable in both cases. This data highlight (1) the ongoing importance of cytogenetic analysis for the diagnostic work-up of myeloid neoplasms as it may guide targeted therapy and (2) remission under ruxolitinib may only be short-termed in JAK2 fusion genes but it may be an important bridging therapy prior to ASCT.
- Published
- 2015
- Full Text
- View/download PDF
33. Recurrent CEP85L-PDGFRB fusion in patient with t(5;6) and imatinib-responsive myeloproliferative neoplasm with eosinophilia.
- Author
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Winkelmann N, Hidalgo-Curtis C, Waghorn K, Score J, Dickinson H, Jack A, Ali S, and Cross NC
- Subjects
- Amino Acid Sequence, Antineoplastic Agents therapeutic use, Base Sequence, Benzamides therapeutic use, Chromosome Breakpoints, Chromosomes, Human, Pair 5, Chromosomes, Human, Pair 6, Humans, Imatinib Mesylate, Male, Middle Aged, Myeloproliferative Disorders drug therapy, Piperazines therapeutic use, Protein Kinase Inhibitors therapeutic use, Pyrimidines therapeutic use, Treatment Outcome, Eosinophilia complications, Myeloproliferative Disorders complications, Myeloproliferative Disorders genetics, Oncogene Proteins, Fusion genetics, Receptor, Platelet-Derived Growth Factor alpha genetics, Receptor, Platelet-Derived Growth Factor beta genetics, Translocation, Genetic
- Abstract
Fusion genes involving the catalytic domain of tyrosine kinases (TKs) play an important role in the pathogenesis of hematological malignancies and solid tumors. In BCR-ABL1-negative myeloproliferative neoplasms (MPNs) several different tyrosine kinase fusion events have been described, most commonly involving the genes encoding the platelet-derived growth factor receptor alpha (PDGFRA) or beta (PDGFRB). Since the introduction of small molecule kinase inhibitors, TK fusions have emerged as prime therapeutic targets. Here, we report a recurrent CEP85L-PDGFRB fusion in a patient with eosinophilia and an MPN. The fusion was confirmed by specific amplification of the genomic breakpoints and reverse transcription polymerase chain reaction (PCR). The patient was treated with imatinib and achieved hematologic and cytogenetic remission. Minimal residual disease screening over 3 years with nested PCR failed to detect CEP85L-PDGFRB mRNA or genomic DNA, confirming a long-term molecular remission on imatinib.
- Published
- 2013
- Full Text
- View/download PDF
34. Inactivating mutations of the histone methyltransferase gene EZH2 in myeloid disorders.
- Author
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Ernst T, Chase AJ, Score J, Hidalgo-Curtis CE, Bryant C, Jones AV, Waghorn K, Zoi K, Ross FM, Reiter A, Hochhaus A, Drexler HG, Duncombe A, Cervantes F, Oscier D, Boultwood J, Grand FH, and Cross NC
- Subjects
- Cell Differentiation genetics, DNA-Binding Proteins, Enhancer of Zeste Homolog 2 Protein, Female, Genes, Tumor Suppressor, Histone Methyltransferases, Histone-Lysine N-Methyltransferase, Histones genetics, Humans, Lysine genetics, Male, Polycomb Repressive Complex 2, Proteins genetics, Transcription Factors, Genes, Regulator
- Abstract
Abnormalities of chromosome 7q are common in myeloid malignancies, but no specific target genes have yet been identified. Here, we describe the finding of homozygous EZH2 mutations in 9 of 12 individuals with 7q acquired uniparental disomy. Screening of a total of 614 individuals with myeloid disorders revealed 49 monoallelic or biallelic EZH2 mutations in 42 individuals; the mutations were found most commonly in those with myelodysplastic/myeloproliferative neoplasms (27 out of 219 individuals, or 12%) and in those with myelofibrosis (4 out of 30 individuals, or 13%). EZH2 encodes the catalytic subunit of the polycomb repressive complex 2 (PRC2), a highly conserved histone H3 lysine 27 (H3K27) methyltransferase that influences stem cell renewal by epigenetic repression of genes involved in cell fate decisions. EZH2 has oncogenic activity, and its overexpression has previously been causally linked to differentiation blocks in epithelial tumors. Notably, the mutations we identified resulted in premature chain termination or direct abrogation of histone methyltransferase activity, suggesting that EZH2 acts as a tumor suppressor for myeloid malignancies.
- Published
- 2010
- Full Text
- View/download PDF
35. A polymorphism associated with STAT3 expression and response of chronic myeloid leukemia to interferon α.
- Author
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Kreil S, Waghorn K, Ernst T, Chase A, White H, Hehlmann R, Reiter A, Hochhaus A, and Cross NC
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Child, Drug Resistance, Neoplasm genetics, Female, Humans, Male, Middle Aged, STAT3 Transcription Factor genetics, Signal Transduction genetics, Young Adult, Gene Expression Regulation, Neoplastic, Interferon-alpha therapeutic use, Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy, Leukemia, Myelogenous, Chronic, BCR-ABL Positive genetics, Polymorphism, Single Nucleotide genetics, STAT3 Transcription Factor biosynthesis
- Abstract
Interferon alpha (IFN) induces variable responses in chronic myeloid leukemia (CML), with 8-30% of early chronic phase cases achieving a complete cytogenetic response. We hypothesized that polymorphic differences in genes encoding IFN signal transduction components might account for different patient responses. We studied 174 IFN-treated patients, of whom 79 achieved less than 35% Philadelphia-chromosome (Ph) positive metaphases (responders) and 95 failed to show any cytogenetic response (more than 95% Ph-positive metaphases; non-responders). We compared 17 single nucleotide polymorphisms (SNPs) at IFNAR1, IFNAR2, JAK1, TYK2, STAT1, STAT3 and STAT5a/b between the two groups and found a significant difference for rs6503691, a SNP tightly linked to STAT5a, STAT5b and STAT3 (minor allele frequency 0.16 for non-responders; 0.06 for responders, P=0.007). Levels of STAT3 mRNA correlated with rs6503691 genotype (P<0.001) as assessed by real time quantitative PCR and therefore we conclude that rs6503691 is associated with the STAT3 expression levels and response of CML patients to IFN.
- Published
- 2010
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36. Heterogeneous prognostic impact of derivative chromosome 9 deletions in chronic myelogenous leukemia.
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Kreil S, Pfirrmann M, Haferlach C, Waghorn K, Chase A, Hehlmann R, Reiter A, Hochhaus A, and Cross NC
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Blast Crisis genetics, Child, Disease Progression, Female, Fusion Proteins, bcr-abl genetics, Fusion Proteins, bcr-abl metabolism, Genes, abl genetics, Humans, Karyotyping, Leukemia, Myelogenous, Chronic, BCR-ABL Positive diagnosis, Leukemia, Myelogenous, Chronic, BCR-ABL Positive therapy, Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative diagnosis, Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative genetics, Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative therapy, Male, Middle Aged, Prognosis, Proto-Oncogene Proteins c-bcr genetics, Survival Rate, Chromosome Deletion, Chromosomes, Human, Pair 9 genetics, Leukemia, Myelogenous, Chronic, BCR-ABL Positive genetics
- Abstract
Derivative chromosome 9 deletions are seen in 10% to 15% of patients with chronic myelogenous leukemia and have been associated with a poor prognosis; however, no studies have been performed in the context of a randomized clinical trial. We developed a DNA-based deletion screen and investigated 339 chronic phase patients treated with interferon-alpha as first-line therapy in 3 controlled German studies with a median observation time of 7 years. Deletions were detected in pretreatment DNA of 59 of 339 (17%) patients. Of these, 21 spanned the ABL/BCR junction and 38 were centromeric (n = 20) or telomeric (n = 18) of the breakpoint. There was no significant difference in overall survival between deleted and nondeleted patients. Patients with breakpoint-spanning deletions had poorer survival compared with patients without deletions (4.7 versus 7.8 years; P = .003), but this was not significant when censored at allogeneic stem cell transplantation (n = 129) or imatinib (n = 62) treatment in the first chronic phase (P = .078). Unexpectedly, deletions that did not span the breakpoint were associated with improved survival compared with cases without deletions (P = .001). Multiple Cox regression analysis indicated that deletion status (P = .007), age (P = .018), and spleen enlargement (P < .001) were significant independent indicators of survival and confirmed that only deletions spanning the ABL/BCR breakpoint were associated with an adverse prognosis (P = .039).
- Published
- 2007
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37. Low-dose imatinib mesylate leads to rapid induction of major molecular responses and achievement of complete molecular remission in FIP1L1-PDGFRA-positive chronic eosinophilic leukemia.
- Author
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Jovanovic JV, Score J, Waghorn K, Cilloni D, Gottardi E, Metzgeroth G, Erben P, Popp H, Walz C, Hochhaus A, Roche-Lestienne C, Preudhomme C, Solomon E, Apperley J, Rondoni M, Ottaviani E, Martinelli G, Brito-Babapulle F, Saglio G, Hehlmann R, Cross NC, Reiter A, and Grimwade D
- Subjects
- Benzamides, Chronic Disease, DNA Primers chemistry, Exons, Humans, Imatinib Mesylate, Kinetics, Polymerase Chain Reaction, Remission Induction, Time Factors, Treatment Outcome, United Kingdom, Antineoplastic Agents administration & dosage, Hypereosinophilic Syndrome drug therapy, Hypereosinophilic Syndrome genetics, Piperazines administration & dosage, Pyrimidines administration & dosage, Receptor, Platelet-Derived Growth Factor alpha biosynthesis, mRNA Cleavage and Polyadenylation Factors biosynthesis
- Abstract
The FIP1L1-PDGFRA fusion gene is a recurrent molecular lesion in eosinophilia-associated myeloproliferative disorders, predicting a favorable response to imatinib mesylate. To investigate its prevalence, 376 patients with persistent unexplained hypereosinophilia were screened by the United Kingdom reference laboratory, revealing 40 positive cases (11%). To determine response kinetics following imatinib, real-time quantitative-polymerase chain reaction (RQ-PCR) assays were developed and evaluated in samples accrued from across the European LeukemiaNet. The FIP1L1-PDGFRA fusion transcript was detected at a sensitivity of 1 in 10(5) in serial dilution of the EOL-1 cell line. Normalized FIP1L1-PDGFRA transcript levels in patient samples prior to imatinib varied by almost 3 logs. Serial monitoring was undertaken in patients with a high level of FIP1L1-PDGFRA expression prior to initiation of imatinib (100 mg/d-400 mg/d). Overall, 11 of 11 evaluable patients achieved at least a 3-log reduction in FIP1L1-PDGFRA fusion transcripts relative to the pretreatment level within 12 months, with achievement of molecular remission in 9 of 11 (assay sensitivities 1 in 10(3)-10(5)). In 2 patients, withdrawal of imatinib was followed by a rapid rise in FIP1L1-PDGFRA transcript levels. Overall, these data are consistent with the exquisite sensitivity of the FIP1L1-PDGFRalpha fusion to imatinib, as compared with BCR-ABL, and underline the importance of RQ-PCR monitoring to guide management using molecularly targeted therapies.
- Published
- 2007
- Full Text
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38. Durable responses to imatinib in patients with PDGFRB fusion gene-positive and BCR-ABL-negative chronic myeloproliferative disorders.
- Author
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David M, Cross NC, Burgstaller S, Chase A, Curtis C, Dang R, Gardembas M, Goldman JM, Grand F, Hughes G, Huguet F, Lavender L, McArthur GA, Mahon FX, Massimini G, Melo J, Rousselot P, Russell-Jones RJ, Seymour JF, Smith G, Stark A, Waghorn K, Nikolova Z, and Apperley JF
- Subjects
- Adult, Aged, Aged, 80 and over, Benzamides, Biomarkers, Tumor blood, Child, Child, Preschool, Drug Evaluation, Eosinophilia etiology, Female, Follow-Up Studies, Humans, Imatinib Mesylate, Infant, Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative blood, Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative drug therapy, Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative genetics, Male, Middle Aged, Myeloproliferative Disorders blood, Myeloproliferative Disorders genetics, Oncogene Proteins, Fusion genetics, RNA, Messenger blood, RNA, Neoplasm blood, Receptor, Platelet-Derived Growth Factor beta genetics, Retrospective Studies, Reverse Transcriptase Polymerase Chain Reaction, Translocation, Genetic, Treatment Outcome, Antineoplastic Agents therapeutic use, Fusion Proteins, bcr-abl blood, Myeloproliferative Disorders drug therapy, Oncogene Proteins, Fusion blood, Piperazines therapeutic use, Protein Kinase Inhibitors therapeutic use, Pyrimidines therapeutic use, Receptor, Platelet-Derived Growth Factor beta blood
- Abstract
Fusion genes derived from the platelet-derived growth factor receptor beta (PDGFRB) or alpha (PDGFRA) play an important role in the pathogenesis of BCR-ABL-negative chronic myeloproliferative disorders (CMPDs). These fusion genes encode constitutively activated receptor tyrosine kinases that can be inhibited by imatinib. Twelve patients with BCR-ABL-negative CMPDs and reciprocal translocations involving PDGFRB received imatinib for a median of 47 months (range, 0.1-60 months). Eleven had prompt responses with normalization of peripheral-blood cell counts and disappearance of eosinophilia; 10 had complete resolution of cytogenetic abnormalities and decrease or disappearance of fusion transcripts as measured by reverse transcriptase-polymerase chain reaction (RT-PCR). Updates were sought from 8 further patients previously described in the literature; prompt responses were described in 7 and persist in 6. Our data show that durable hematologic and cytogenetic responses are achieved with imatinib in patients with PDGFRB fusion-positive, BCR-ABL-negative CMPDs.
- Published
- 2007
- Full Text
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39. Minimal molecular response in polycythemia vera patients treated with imatinib or interferon alpha.
- Author
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Jones AV, Silver RT, Waghorn K, Curtis C, Kreil S, Zoi K, Hochhaus A, Oscier D, Metzgeroth G, Lengfelder E, Reiter A, Chase AJ, and Cross NC
- Subjects
- Adult, Aged, Alleles, Amino Acid Substitution, Benzamides, Biomarkers blood, Dose-Response Relationship, Drug, Female, Hematopoiesis drug effects, Hematopoiesis genetics, Humans, Imatinib Mesylate, Janus Kinase 2, Male, Middle Aged, Polycythemia Vera blood, Polycythemia Vera genetics, Protein-Tyrosine Kinases antagonists & inhibitors, Protein-Tyrosine Kinases genetics, Proto-Oncogene Proteins antagonists & inhibitors, Proto-Oncogene Proteins genetics, Recombinant Proteins, Remission Induction methods, Antineoplastic Agents administration & dosage, Interferon Type I administration & dosage, Piperazines administration & dosage, Polycythemia Vera drug therapy, Protein Kinase Inhibitors administration & dosage, Pyrimidines administration & dosage
- Abstract
Imatinib and recombinant interferon alpha (rIFNalpha) can induce remission in polycythemia vera (PV) patients, but gauging the depth of responses has not been possible due to lack of a specific disease marker. We found that patients undergoing imatinib (n = 14) or rIFNalpha (n = 7) therapy remained strongly positive for V617F JAK2, although there was a significant reduction in the median percentage of mutant alleles that correlated with hematologic response (P = .001). Furthermore, individuals who achieved complete hematologic remission had lower levels of V617F than those who did not (P = .001). Of 9 imatinib-treated cases for whom pretreatment samples were available, 7 with no or partial hematologic responses showed a marginal increase (median, 1.2-fold; range, 1.0-1.5) in the percentage of V617F alleles on treatment, whereas the 2 patients who achieved complete hematologic remission showed a 2- to 3-fold reduction. Our data indicate that, although PV patients may benefit from imatinib or rIFNalpha, molecular responses are relatively modest.
- Published
- 2006
- Full Text
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40. In-hospital formula supplementation of healthy breastfeeding newborns.
- Author
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Gagnon AJ, Leduc G, Waghorn K, Yang H, and Platt RW
- Subjects
- Adult, Canada, Female, Health Promotion, Hospitals, Maternity standards, Humans, Infant, Newborn, Length of Stay, Male, Maternal Behavior psychology, Milk, Human physiology, Parity, Pregnancy, Referral and Consultation, Time Factors, Breast Feeding, Dietary Supplements adverse effects, Infant Formula administration & dosage, Nurse Midwives psychology, Social Support
- Abstract
The UNICEF/WHO Baby-Friendly Hospital Initiative suggests that breastfeeding activities in hospital are important to later breastfeeding. Understanding reasons for in-hospital supplementation may help to optimize the successful implementation of this initiative. The objective was to identify predictors of in-hospital initial formula supplementation of healthy, breastfeeding newborns. The authors analyzed 564 Canadian mother-infant pairs and interviewed nurses. Half of the study infants (47.9%) received formula in hospital; the median age at first supplementation was 8.4 hours. Risk for supplementation was affected by birth occurring between 7 PM and 9 AM (hazard ratio [HR] varied with time) and high maternal trait anxiety (HR=1.61, 95% confidence interval [CI]=1.01, 2.59). The following variables were protective against supplementation: planning to exclusively breastfeed (HR=0.46, 95% CI=0.33, 0.64), planning to breastfeed for >or=3 months (HR=0.56, 95% CI=0.37-0.86), childbirth education (HR=0.61, 95% CI=0.43, 0.86), mother born in Canada (HR=0.68, 95% CI=0.53, 0.87), completion of community college (HR=0.76, 95% CI=0.59, 0.98), male infant (HR=0.78, 95% CI=0.61, 0.99), and breastfeeding at delivery (HR varied with time). Nurses reported breastfeeding problems, infant behavior, and maternal fatigue as reasons for supplementing. Reassessing patterns of night feeds and encouraging breastfeeding at delivery may decrease supplementation. Trait anxiety reduction and the role of infant gender in supplementation merit further study.
- Published
- 2005
- Full Text
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41. Widespread occurrence of the JAK2 V617F mutation in chronic myeloproliferative disorders.
- Author
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Jones AV, Kreil S, Zoi K, Waghorn K, Curtis C, Zhang L, Score J, Seear R, Chase AJ, Grand FH, White H, Zoi C, Loukopoulos D, Terpos E, Vervessou EC, Schultheis B, Emig M, Ernst T, Lengfelder E, Hehlmann R, Hochhaus A, Oscier D, Silver RT, Reiter A, and Cross NC
- Subjects
- Case-Control Studies, Chronic Disease, Female, Homozygote, Humans, Janus Kinase 2, Male, Microsatellite Repeats, Molecular Epidemiology, Myeloproliferative Disorders epidemiology, Prevalence, Signal Transduction genetics, Mutation, Missense, Myeloproliferative Disorders genetics, Protein-Tyrosine Kinases genetics, Proto-Oncogene Proteins genetics
- Abstract
The analysis of rare chromosomal translocations in myeloproliferative disorders has highlighted the importance of aberrant tyrosine kinase signaling in the pathogenesis of these diseases. Here we have investigated samples from 679 patients and controls for the nonreceptor tyrosine kinase JAK2 V617F mutation. Of the 480 myeloproliferative disorder (MPD) samples, the proportion of positive cases per disease subtype was 30 (20%) of 152 for atypical or unclassified MPD, 2 of 134 (2%) for idiopathic hypereosinophilic syndrome, 58 of 72 (81%) for polycythemia vera, 24 of 59 (41%) essential thrombocythemia (ET), and 15 of 35 (43%) for idiopathic myelofibrosis. V617F was not identified in patients with systemic mastocytosis (n = 28), chronic or acute myeloid leukemia (n = 35), secondary erythrocytosis (n = 4), or healthy controls (n = 160). Homozygosity for V617F was seen in 43% of mutant samples and was closely correlated with chromosome 9p uniparental disomy. Homozygosity was significantly less common in ET compared with other MPD subtypes. In 53 cases analyzed, the median level of PRV1 expression was significantly higher in V617F-positive cases compared with cases without the mutation. We conclude that V617F is widespread in MPDs. Detection of this acquired mutation is likely to have a major impact on the way patients with MPD are diagnosed, as well as serving as an obvious target for signal transduction therapy.
- Published
- 2005
- Full Text
- View/download PDF
42. Indicators nurses employ in deciding to test for hyperbilirubinemia.
- Author
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Gagnon AJ, Waghorn K, Jones MA, and Yang H
- Subjects
- Attitude of Health Personnel, Birth Weight, Case-Control Studies, Clinical Competence standards, Feeding Behavior, Female, Gestational Age, Health Knowledge, Attitudes, Practice, Humans, Hyperbilirubinemia blood, Infant Behavior, Infant, Newborn, Jaundice etiology, Logistic Models, Male, Motor Activity, Nursing Assessment standards, Nursing Evaluation Research, Nursing Staff, Hospital education, Predictive Value of Tests, Surveys and Questionnaires, Time Factors, Decision Making, Hyperbilirubinemia diagnosis, Hyperbilirubinemia nursing, Neonatal Screening nursing, Nursing Assessment methods, Nursing Staff, Hospital psychology, Patient Selection
- Abstract
Objective: To identify the indicators nurses employ in deciding to test healthy full-term newborns for total serum bilirubin in the absence of a written protocol., Design: Secondary analysis of data available on 130 mother-newborn pairs and informal interviews of 30 postpartum unit nurses., Setting: Two university teaching hospitals., Participants: All tested newborns and a 33% random sample of remaining newborns from a control group data set created during a previous study and a convenience sample of postpartum nurses from all shifts., Measurement: Outcome data were obtained from a review of records. Background data were obtained from a review of records and questionnaires. Nurse data were obtained through a modified form of participant observation., Results: Ninety-one percent of newborns tested for bilirubin were tested unnecessarily. In logistic regression analyses, variables predictive of nurse-driven total serum bilirubin testing were presence of jaundice, odds ratio (OR) = 31.95 (95% confidence interval, 6.71, 152.03), and feeding frequency, OR = 0.28 (0.11, 0.72). Identifying both presence and location of jaundice simultaneously did not significantly predict testing, OR = 1.82 (0.66, 5.04). Fifty-three percent of nurses who were interviewed identified both the presence of jaundice and feeding as indicators to consider for testing., Conclusion: Newborns are overtested for bilirubin. Indicators used by nurses in deciding to test a healthy newborn for total serum bilirubin are the presence of jaundice and feeding frequency. Nurses who assess feeding frequency are less likely to order bilirubin testing.
- Published
- 2001
- Full Text
- View/download PDF
43. One-to-one nurse labor support of nulliparous women stimulated with oxytocin.
- Author
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Gagnon AJ and Waghorn K
- Subjects
- Cesarean Section nursing, Female, Humans, Pregnancy, Pregnancy Outcome, Dystocia drug therapy, Dystocia nursing, Nursing Care methods, Obstetric Nursing methods, Oxytocin therapeutic use
- Abstract
Objective: To compare the benefits of one-to-one nurse labor support with the benefits of usual intrapartum nursing care in women stimulated with oxytocin., Design: A secondary analysis of a randomized controlled trial., Setting: A 637-bed university hospital., Participants: One hundred nulliparous women 37 weeks or more gestation, carrying singletons, in labor with vertex presentation, stimulated with oxytocin, less than 5 cm dilated at baseline, and not scheduled for cesarean delivery or induction nor having paid labor support present., Interventions: One-to-one care consisted of the presence of a nurse during labor and birth who provided emotional support, physical comfort, and instruction on relaxation and coping techniques. Usual care consisted of care for 2-3 laboring women with supportive activities varying by nurse., Main Outcome Measure: Cesarean delivery., Results: A beneficial trend because of one-to-one nurse support, with a 56% reduction in risk of total cesarean deliveries [RR of experimental vs. control = 0.44 (95% confidence interval = 0.19 to 1.01)]., Conclusion: The beneficial trend in reducing cesarean deliveries attributed to one-to-one nursing in women stimulated with oxytocin suggests that continuous support by intrapartum nursing staff may benefit women stimulated with oxytocin during labor.
- Published
- 1999
- Full Text
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44. A randomized trial of one-to-one nurse support of women in labor.
- Author
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Gagnon AJ, Waghorn K, and Covell C
- Subjects
- Adult, Female, Humans, Nursing Evaluation Research, Pregnancy, Pregnancy Outcome, Social Support, Labor, Obstetric psychology, Nurse-Patient Relations, Obstetric Nursing organization & administration, Primary Nursing organization & administration
- Abstract
Background: Health researchers and provider groups have recommended that women in labor should receive continuous professional support. The objective of our study was to compare the risks and benefits of one-to-one nurse labor support with usual intrapartum nursing care., Methods: A randomized, controlled trial was conducted in a 637-bed university hospital in Montreal, Quebec, with 413 nulliparous women who were at more than 37 weeks' gestation, carrying singletons, and in labor. Women with scheduled cesarean section, scheduled induction, breech presentation, presence of paid labor support, or cervical dilatation over 4 cm were excluded. One-to-one care consisted of the presence of a nurse during labor and birth who provided emotional support, physical comfort, and instruction for relaxation and coping techniques. Usual care consisted of care for two or three laboring women with various types of supportive activities., Results: A beneficial trend due to one-to-one nurse support was found with a 17 percent reduction in risk of oxytocin stimulation (relative risk of experimental vs control = 0.83; 95% confidence interval = 0.67, 1.04). No significant differences were found in overall labor durations and overall rates of total cesarean section, cesarean section for cephalopelvic disproportion, epidural analgesia, admission to the neonatal intensive care unit, instrumental vaginal delivery, and perineal trauma., Conclusions: The beneficial trend attributed to one-to-one nursing in reduction of oxytocin stimulation suggests that implementation of recommendations for continuous professional support by intrapartum nursing staff may be appropriate in North America.
- Published
- 1997
45. Relationship of episiotomy to perineal trauma and morbidity, sexual dysfunction, and pelvic floor relaxation.
- Author
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Klein MC, Gauthier RJ, Robbins JM, Kaczorowski J, Jorgensen SH, Franco ED, Johnson B, Waghorn K, Gelfand MM, and Guralnick MS
- Subjects
- Adolescent, Adult, Analysis of Variance, Canada, Chi-Square Distribution, Cohort Studies, Female, Humans, Pain, Postoperative etiology, Parity, Perineum physiopathology, Postoperative Complications physiopathology, Pregnancy, Regression Analysis, Urination Disorders etiology, Episiotomy adverse effects, Muscle Relaxation, Pelvic Floor physiopathology, Perineum injuries, Postoperative Complications etiology, Sexual Dysfunction, Physiological etiology
- Abstract
Objective: Our purpose was to compare consequences for women of receiving versus not receiving median episiotomy early and 3 months post partum on the outcomes perineal pain, urinary and pelvic floor functioning by electromyography, and sexual functioning and to analyze the relationship between episiotomy and third- and fourth-degree tears., Study Design: A secondary cohort analysis was performed of participants within a randomized clinical trial, analyzed by type of perineal trauma and pain, pelvic floor, and sexual consequences of such trauma, while controlling for trial arm. The study was conducted in three university or community hospitals; 356 primiparous and 341 multiparous women were studied., Results: Early and 3-month-postpartum perineal pain was least for women who gave birth with an intact perineum. Spontaneous perineal tears were less painful than episiotomy. Sexual functioning was best for women with an intact perineum or perineal tears. Postpartum urinary and pelvic floor symptoms were similar in all perineal groups. At 3 months post partum those delivered with an intact perineum had the strongest pelvic floor musculature, those with episiotomy the weakest. Among primiparous women third- and fourth-degree tears were associated with median episiotomy (46/47). After forceps births were removed and 21 other variables potentially associated within such tears were controlled for, episiotomy was strongly associated with third- and fourth-degree tears (odds ratio +22.08, 95% confidence interval 2.84 to 171.53). Physicians using episiotomy at high rates also used other procedures, including cesarean section, more frequently., Conclusion: Perineal and pelvic floor morbidity was greatest among women receiving median episiotomy versus those remaining intact or sustaining spontaneous perineal tears. Median episiotomy was causally related to third- and fourth-degree tears. Those using episiotomy at the highest rates were more likely use other interventions as well. Episiotomy use should be restricted to specified fetal-maternal indications.
- Published
- 1994
- Full Text
- View/download PDF
46. [Does episiotomy prevent perineal trauma and pelvic floor relaxation?].
- Author
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Klein MC, Gauthier RJ, Jorgensen SH, Robbins JM, Kaczorowski J, Johnson B, Corriveau M, Westreich R, Waghorn K, and Gelfand MM
- Subjects
- Adult, Female, Humans, Muscle Hypotonia prevention & control, Pelvic Floor, Pregnancy, Rupture, Episiotomy, Perineum injuries
- Published
- 1993
47. Does episiotomy prevent perineal trauma and pelvic floor relaxation?
- Author
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Klein MC, Gauthier RJ, Jorgensen SH, Robbins JM, Kaczorowski J, Johnson B, Corriveau M, Westreich R, Waghorn K, and Gelfand MM
- Subjects
- Adult, Coitus, Female, Humans, Labor Stage, Second, Pain, Postoperative, Parity, Pelvic Floor, Pregnancy, Rectum injuries, Time Factors, Urinary Incontinence prevention & control, Wounds and Injuries etiology, Wounds and Injuries prevention & control, Episiotomy adverse effects, Episiotomy methods, Muscle Hypotonia prevention & control, Perineum injuries
- Abstract
Objective: To compare the outcomes of the current practice of liberally or routinely employing episiotomy to prevent perineal tears and pelvic floor relaxation (control group) to a policy of restricting episiotomy use to specific fetal and maternal indications (experimental group)., Design: A randomized controlled trial (RCT)., Setting: Three university hospitals in Montreal., Subjects: Seven hundred three low-risk women enrolled at 30 to 34 weeks of gestation were randomized late in labor to the designated trial arm, by parity, and followed up to 3 months postpartum., Main Outcome Measures: Antepartum and postpartum information on perineal trauma and pain, pelvic floor symptoms (urinary incontinence), and sexual activity was collected through the use of standard questionnaires; pelvic floor function was measured by electromyographic (EMG) perineometry., Results: Restricting episiotomy use in primiparous women was associated with similar sutured perineal trauma to the liberal or routine approach. Multiparous women in the restricted episiotomy group more often gave birth with an intact perineum (31% compared with 19%, odds ratio (OR) = 1.85, 95% confidence interval (CI) = 1.09 to 3.16). All but one 3rd/4th-degree perineal tear was associated with median episiotomy (46 of 47 in primiparous women and 6 of 6 among multiparous women). No difference between trial groups was found in postpartum perineal pain, antepartum and 3-month postpartum EMG perineometry, and urinary and pelvic floor symptoms., Conclusions: We found no evidence that liberal or routine use of episiotomy prevents perineal trauma or pelvic floor relaxation. Virtually all severe perineal trauma was associated with median episiotomy. Restriction of episiotomy use among multiparous women resulted in significantly more intact perineums and less perineal suturing.
- Published
- 1992
- Full Text
- View/download PDF
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