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Battmer R.-D.,UKB | Borel S.,Beaujon | Brendel M.,Advanced Bionics | Buchner A.,MHH | And 13 more authors.
Cochlear Implants International | Year: 2015

Objective: To compare the fitting time requirements and the efficiency in achieving improvements in speech perception during the first 6 months after initial stimulation of computer-assisted fitting with the Fitting to Outcome eXpert’ (FOX) and a standard clinical fitting procedure. Method: Twenty-seven post-lingually deafened adults, newly implanted recipients of the Advanced Bionics HiRes 90K™ cochlear implant from Germany, the UK, and France took part in a controlled, randomized, clinical study. Speech perception was measured for all participants and fitting times were compared across groups programmed using FOX and conventional programming methods. Results: The fitting time for FOX was significantly reduced at 14 days (P< 0.001) but equivalent over the 6- month period. The groups were not well matched for duration of deafness; therefore, speech perception could not be compared across groups. Discussion: Despite including more objective measures of performance than a standard fitting approach and the adjustment of a greater range of parameters during initial fitting, FOX did not add to the overall fitting time when compared to the conventional approach. FOX significantly reduced the fitting time in the first 2 weeks and by providing a standard fitting protocol, reduced variability across centres. Conclusions: FOX computer-assisted fitting can be successfully used at switch on, in different clinical environments, reducing fitting time in the first 2 weeks and is efficient at providing a usable program. © W. S. Maney & Son Ltd 2015.


Andersen C.L.,Roskilde Hospital | Andersen C.L.,Copenhagen University | Mcmullin M.F.,Queen's University of Belfast | Ejerblad E.,Uppsala University Hospital | And 17 more authors.
British Journal of Haematology | Year: 2013

Inhibition of histone deacetylases may be an important target in patients with myeloproliferative neoplasms. This investigator-initiated, non-randomized, open-label phase II multi-centre study included 63 patients (19 essential thrombocythaemia, 44 polycythaemia vera) from 15 centres. The primary objective was to evaluate if vorinostat was followed by a decline in clonal myeloproliferation as defined by European Leukaemia Net. Thirty patients (48%) completed the intervention period (24 weeks of therapy). An intention-to-treat response rate of 35% was identified. Pruritus was resolved [19% to 0% (P = 0·06)] and the prevalence of splenomegaly was lowered from 50% to 27% (P = 0·03). Sixty-five per cent of the patients experienced a decrease in JAK2 V617F allele burden (P = 0·006). Thirty-three patients (52% of patients) discontinued study drug before end of intervention due to adverse events (28 patients) or lack of response (5 patients). In conclusion, vorinostat showed effectiveness by normalizing elevated leucocyte and platelet counts, resolving pruritus and significantly reducing splenomegaly. However, vorinostat was associated with significant side effects resulting in a high discontinuation rate. A lower dose of vorinostat in combination with conventional and/or novel targeted therapies may be warranted in future studies. © 2013 John Wiley & Sons Ltd.


Loukopoulos I.,National and Kapodistrian University of Athens | Sfiniadakis I.,Naval Hospital of Athens | Pillai A.,Guys and St Thomas | Konstantoulakis M.,National and Kapodistrian University of Athens | And 4 more authors.
Journal of Investigative Surgery | Year: 2014

Introduction: Hepatocyte transplantation is proposed as a solution for liver failure. The allotransplantation of hepatocytes has been studied extensively, however, graft rejection remains a major problem. The aim of the present study was to evaluate the immunosuppressive activity of mycophenolate mofetil (MMF), sirolimus, and their combination in an experimental model of hepatocyte allotransplantation in rats with acute liver failure. Materials and methods: Five male Wistar rats were used as hepatocyte donors and 60 male Lewis rats as recipients. The recipients were divided into five groups of 12 animals each. Group 1: no treatment. Group 2: cyclosporine. Group 3: sirolimus. Group 4: MMF. Group 5: MMF and sirolimus. All surviving animals were preserved for 15 days. For the induction of acute liver failure the recipients were injected with N-dimethyl-nitrosamine 24 hr before transplantation. The isolated hepatocytes were transplanted intrasplenically. Results: Analysis of the results showed a statistically significant prolongation of animal survival for groups 3, 4, and 5. More animals in group 5 survived than those in groups 3 and 4, although the difference was not statistically significant. Transplant hepatocyte survival was significantly better in groups 3, 4, and 5. Hepatocytes transplanted in the spleen of animals of group 5 showed better survival compared with those of groups 3 and 4. Conclusion: Use of MMF and sirolimus, as monotherapy or in combination, is both effective and safe as immunosuppressive treatment in hepatocyte transplantation, as was proven in this experimental protocol. © 2014 Informa Healthcare USA, Inc.


Swerdlow A.J.,Institute of Cancer Research | Cooke R.,Institute of Cancer Research | Bates A.,Southampton General Hospital | Cunningham D.,Royal Marsden Hospital | And 13 more authors.
Journal of the National Cancer Institute | Year: 2014

Background: Modern treatment of Hodgkin's lymphoma (HL) has transformed its prognosis but causes late effects, including premature menopause. Cohort studies of premature menopause risks after treatment have been relatively small, and knowledge about these risks is limited.Methods: Nonsurgical menopause risk was analyzed in 2127 women treated for HL in England and Wales at ages younger than 36 years from 1960 through 2004 and followed to 2003 through 2012. Risks were estimated using Cox regression, modified Poisson regression, and competing risks. All statistical tests were two-sided.Results: During follow-up, 605 patients underwent nonsurgical menopause before age 40 years. Risk of premature menopause increased more than 20-fold after ovarian radiotherapy, alkylating chemotherapy other than dacarbazine, or BEAM (bis-chloroethylnitrosourea [BCNU], etoposide, cytarabine, melphalan) chemotherapy for stem cell transplantation, but was not statistically significantly raised after adriamycin, bleomycin, vinblastine, dacarbazine (ABVD). Menopause generally occurred sooner after ovarian radiotherapy (62.5% within five years of =5 Gy treatment) and BEAM (50.9% within five years) than after alkylating chemotherapy (24.2% within five years of =6 cycles), and after treatment at older than at younger ages. Cumulative risk of menopause by age 40 years was 81.3% after greater than or equal to 5Gy ovarian radiotherapy, 75.3% after BEAM, 49.1% after greater than or equal to 6 cycles alkylating chemotherapy, 1.4% after ABVD, and 3.0% after solely supradiaphragmatic radiotherapy. Tables of individualized risk information for patients by future period, treatment type, dose and age are provided.Conclusions: Patients treated with HL need to plan intended pregnancies using personalized information on their risk of menopause by different future time points. © The Author 2014. Published by Oxford University Press. All rights reserved.


Swerdlow A.J.,Institute of Cancer Research | Cooke R.,Institute of Cancer Research | Bates A.,Southampton General Hospital | Cunningham D.,Royal Marsden Hospital | And 13 more authors.
Journal of Clinical Oncology | Year: 2012

Purpose: To investigate breast cancer risk after supradiaphragmatic radiotherapy administered to young women with Hodgkin's lymphoma (HL) in a much larger cohort than previously to provide data for patient follow-up and screening individualized according to treatment type, age, and time point during follow-up. Patients and Methods: Breast cancer risk was assessed in 5,002 women in England and Wales treated for HL with supradiaphragmatic radiotherapy at age < 36 years from 1956 to 2003, who underwent follow-up with 97% completeness until December 31, 2008. Results: Breast cancer or ductal carcinoma in situ developed in 373 patients, with a standardized incidence ratio (SIR) of 5.0 (95% CI, 4.5 to 5.5). SIRs were greatest for those treated at age 14 years (47.2; 95% CI, 28.0 to 79.8) and continued to remain high for at least 40 years. The maximum absolute excess risk was at attained ages 50 to 59 years. Alkylating chemotherapy or pelvic radiotherapy diminished the risk, but only for women treated at age ≥ 20 years, not for those treated when younger. Cumulative risks were tabulated in detail; for 40-year follow-up, the risk for patients receiving ≥ 40 Gy mantle radiotherapy at young ages was 48%. Conclusion: This article provides individualized risk estimates based on large numbers for patients with HL undergoing follow-up after radiotherapy at young ages. Follow-up of such women needs to continue for 40 years or longer and may require more-intensive screening regimens than those in national general population programs. Special consideration is needed of potential measures to reduce breast cancer risk for girls treated with supradiaphragmatic radiotherapy at pubertal ages. © 2012 by American Society of Clinical Oncology.


Andersen C.L.,Roskilde University | Bjorn M.E.,Roskilde University | McMullin M.F.,Queen's University of Belfast | Harrison C.,Guys and St Thomas | And 21 more authors.
Leukemia Research | Year: 2014

YKL-40 regulates vascular endothelial growth factors and induces tumor proliferation. We investigated YKL-40 before and after treatment with vorinostat in 31 polycythemia vera (PV) and 16 essential thrombocythemia (ET) patients. Baseline PV patient levels were 2 times higher than in healthy controls (P<. 0.0001) and 1.7 times higher than in ET (P= 0.02). A significant correlation between YKL-40 at baseline and neutrophils, CRP, LDH, JAK2V617F and platelets in PV patients was observed, as well as a significantly greater reduction of YKL-40 levels in PV patients responding to therapy. YKL-40 might be a novel marker of disease burden and progression in myeloproliferative neoplasms. © 2014 Elsevier Ltd.


Kirubakaran S.,Guys and St. Thomas | Gill J.,Guys and St. Thomas | Rinaldi C.A.,Guys and St. Thomas
PACE - Pacing and Clinical Electrophysiology | Year: 2011

A 64-year-old man with nonischemic dilated cardiomyopathy and a biventricular defibrillator presented with recurrent ventricular fibrillation (VF) and defibrillator shocks. Evaluation of the intracardiac electrograms from his defibrillator demonstrated the consistent initiation of VF by unifocal premature ventricular complexes (PVCs). Noncontact mapping demonstrated the origin of the PVC to be near the left ventricular outflow tract toward the mitral valve ring. Several applications of radiofrequency at this position led to complete cessation of PVCs and prevented further VF. He has not had any further ventricular arrhythmias or defibrillator discharges during follow-up. ©2010, The Authors. Journal compilation ©2010 Wiley Periodicals, Inc.


PubMed | Guys and St Thomas
Type: | Journal: BMJ case reports | Year: 2011

The fish-vertebra sign appears as biconcave lumbar vertebrae with bone softening in lateral and posterior-anterior radiographs of the spine as an exaggeration of the normal concavity of the superior and inferior surfaces of one or more vertebral bodies. This is due to ischaemia of the central growth plate of the spine, and is typically seen in sickle cell disease.

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