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1.
Arch Orthop Trauma Surg ; 143(5): 2317-2324, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-35359162

RESUMO

PURPOSE: Vertebral osteomyelitis (VO) is a severe clinical entity associated with significant morbidity and mortality. Several studies have showed that successful treatment of VO patients leads to significantly improved quality of life (QoL). Nevertheless, QoL levels of these patients remained below those of the general population. There are rarely studies focusing on predicting factors for favourable QoL after surgically treated VO. The aim of this study was to identify factors influencing positively the QoL of patients undergoing surgery for VO. METHODS: We conducted a prospective monocentric study including surgically treated VO patients from 2008 to 2016. Data were collected before (T0) and 1 year (T1) after surgery. Primary outcome was favourable QoL defined as back pain with disability restricting normal life activity with a cutoff value ≥ 12 on Oswestry Disability Index (ODI). ETHICS: Ethical approval was given by the Faculty of Medicine at the University of Cologne (09-182). RESULTS: A total of 119 patients surviving 1 year after surgically treated VO were analysed. Favourable QoL was achieved in 35/119 patients. On multivariate analysis, younger age (hazard ratio = HR: 0.95; 95% CI 0.91-0.99; p = 0.022), lower albumin (HR: 0.9; 0.83-0.98; p = 0.019) an ASA score ≤ 2 (HR:4.24; 95%CI 1.42-12.68; p = 0.010), and a lower preoperative leg pain on the VAS (HR: 0.86; 95% CI 0.76-0.97; p = 0.018) were identified as independent risk factors for favourable QoL. Interestingly, the absence of neurological deficits was not predictive for a favourable outcome by means of QoL. CONCLUSION: One-third of surgically treated VO patients (29%) in our cohort achieved favourable QoL by means of ODI. Our findings can facilitate an estimation of the prognosis when informing the patient before surgery, and underscore that spine disability questionnaires, such as ODI, measuring QoL, are mandatory to evaluate comprehensively the outcome of this entity.


Assuntos
Qualidade de Vida , Coluna Vertebral , Humanos , Estudos Prospectivos , Resultado do Tratamento , Coluna Vertebral/cirurgia , Dor nas Costas/epidemiologia , Dor nas Costas/cirurgia , Vértebras Lombares/cirurgia , Avaliação da Deficiência
2.
Pharmacol Rev ; 74(3): 552-599, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35710137

RESUMO

The nitrogen mustards are powerful cytotoxic and lymphoablative agents and have been used for more than 60 years. They are employed in the treatment of cancers, sarcomas, and hematologic malignancies. Cyclophosphamide, the most versatile of the nitrogen mustards, also has a place in stem cell transplantation and the therapy of autoimmune diseases. Adverse effects caused by the nitrogen mustards on the central nervous system, kidney, heart, bladder, and gonads remain important issues. Advances in analytical techniques have facilitated the investigation of the pharmacokinetics of the nitrogen mustards, especially the oxazaphosphorines, which are prodrugs requiring metabolic activation. Enzymes involved in the metabolism of cyclophosphamide and ifosfamide are very polymorphic, but a greater understanding of the pharmacogenomic influences on their activity has not yet translated into a personalized medicine approach. In addition to damaging DNA, the nitrogen mustards can act through other mechanisms, such as antiangiogenesis and immunomodulation. The immunomodulatory properties of cyclophosphamide are an area of current exploration. In particular, cyclophosphamide decreases the number and activity of regulatory T cells, and the interaction between cyclophosphamide and the intestinal microbiome is now recognized as an important factor. New derivatives of the nitrogen mustards continue to be assessed. Oxazaphosphorine analogs have been synthesized in attempts to both improve efficacy and reduce toxicity, with varying degrees of success. Combinations of the nitrogen mustards with monoclonal antibodies and small-molecule targeted agents are being evaluated. SIGNIFICANCE STATEMENT: The nitrogen mustards are important, well-established therapeutic agents that are used to treat a variety of diseases. Their role is continuing to evolve.


Assuntos
Antineoplásicos , Neoplasias , Compostos de Mostarda Nitrogenada , Antineoplásicos/efeitos adversos , Ciclofosfamida/uso terapêutico , Humanos , Neoplasias/tratamento farmacológico , Nitrogênio/uso terapêutico , Compostos de Mostarda Nitrogenada/uso terapêutico
3.
BMJ Open ; 12(4): e054404, 2022 04 29.
Artigo em Inglês | MEDLINE | ID: mdl-35487718

RESUMO

INTRODUCTION: Breast cancer is still the most common malignancy among women worldwide. The Prospective Breast Cancer Biobank (PBCB) collects blood and urine from patients with breast cancer every 6 or 12 months for 11 years from 2011 to 2030 at two university hospitals in Western Norway. The project aims to identify new biomarkers that enable detection of systemic recurrences at the molecular level. As blood represents the biological interface between the primary tumour, the microenvironment and distant metastases, liquid biopsies represent the ideal medium to monitor the patient's cancer biology for identification of patients at high risk of relapse and for early detection systemic relapse.Including patient-reported outcome measures (PROMs) allows for a vast number of possibilities to compare PROM data with biological information, enabling the study of fatigue and Quality of Life in patients with breast cancer. METHODS AND ANALYSIS: A total of 1455 patients with early-stage breast cancer are enrolled in the PBCB study, which has a one-armed prospective observational design. Participants consent to contribute liquid biopsies (i.e., peripheral blood and urine samples) every 6 or 12 months for 11 years. The liquid biopsies are the basis for detection of circulating tumour cells, circulating tumour DNA (ctDNA), exosomal micro-RNA (miRNA), miRNA in Tumour Educated Platelet and metabolomic profiles. In addition, participants respond to 10 PROM questionnaires collected annually. Moreover, a control group comprising 200 women without cancer aged 25-70 years will provide the same data. ETHICS AND DISSEMINATION: The general research biobank PBCB was approved by the Ministry of Health and Care Services in 2007, by the Regional Ethics Committee (REK) in 2010 (#2010/1957). The PROM (#2011/2161) and the biomarker study PerMoBreCan (#2015/2010) were approved by REK in 2011 and 2015 respectively. Results will be published in international peer reviewed journals. Deidentified data will be accessible on request. TRIAL REGISTRATION NUMBER: NCT04488614.


Assuntos
Neoplasias da Mama , MicroRNAs , Adulto , Idoso , Bancos de Espécimes Biológicos , Biomarcadores , Neoplasias da Mama/diagnóstico , Feminino , Humanos , Biópsia Líquida , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estudos Observacionais como Assunto , Medidas de Resultados Relatados pelo Paciente , Estudos Prospectivos , Qualidade de Vida , Microambiente Tumoral
4.
Sci Rep ; 12(1): 2907, 2022 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-35190584

RESUMO

Physical activity (PA) helps prevention and aftercare of sporadic breast cancer (BC), cardiopulmonary fitness (CPF) being an age-independent predictor of tumor-specific mortality. Therefore, we wanted to identify predictors of CPF (represented by peak oxygen uptake: VO2peak) in BRCA1/2 mutation carriers whose risk of developing BC is high. We used cross-sectional data from 68 BRCA1/2 germline mutation carrying women participating in the randomized, prospective, controlled clinical study LIBRE-1. Assessments included cardiopulmonary exercise testing, medical and lifestyle history plus socioeconomic status. Additionally, the participants completed a psychological questionnaire regarding their attitude, subjective norms, perceived behavior control and intention towards PA. A multivariate logistic regression model was used to identify predictors for participants reaching their age- and sex-adjusted VO2peak reference values. 22 participants (median age: 40 years, interquartile range (IQR) 33-46) were cancer-unaffected and 46 cancer-affected (median age: 44 years, IQR 35-50). The strongest predictor for reaching the reference VO2peak value was attitude towards PA (Odds Ratio 3.0; 95% Confidence Interval 1.3-8.4; p = 0.021). None of the other predictors showed a significant association. A positive attitude towards PA seems to be associated with VO2peak, which should be considered in developing therapeutic and preventive strategies.Trial registrations: NCT02087592; DRKS00005736.


Assuntos
Atitude Frente a Saúde , Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias da Mama/genética , Neoplasias da Mama/prevenção & controle , Teste de Esforço , Exercício Físico/psicologia , Mutação em Linhagem Germinativa , Consumo de Oxigênio , Adulto , Neoplasias da Mama/etiologia , Neoplasias da Mama/psicologia , Estudos Transversais , Feminino , Heterozigoto , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Inquéritos e Questionários
5.
J Infect ; 83(3): 314-320, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34146597

RESUMO

OBJECTIVES: Staphylococcus aureus is the most common cause of pyogenic vertebral osteomyelitis (VO). Studies indicate that S. aureus VO results in poor outcome. We aimed to investigate risk factors for treatment failure in patients with Staphylococcus aureus bloodstream infection (SAB) and VO. METHODS: We conducted a post hoc-analysis of data from a German bi-center prospective SAB cohort (2006-2014). Patients were followed-up for one year. Primary outcome was treatment failure defined as relapse and/or death within one year. RESULTS: A total of 1069 patients with SAB were analyzed, with 92 VO patients. In addition to antibiotic treatment, surgery was performed in 60/92 patients. Treatment failed in 44/92 patients (death, n = 42; relapse, n = 2). Multivariable analysis revealed higher age (HR 1.04 [per year], 95%CI 1.01-1.07), Charlson comorbidity index (HR 1.20, 95%CI 1.06-1.36), presence of neurologic deficits (HR 2.53, 95%CI 1.15-5.53) and local abscess formation (HR 3.35, 95%CI 1.39-8.04) as independent risk factors for treatment failure. In contrast, surgery seemed to be associated with a favourable outcome (HR 0.45 (95%CI 0.20-0.997)). CONCLUSION: SAB patients with VO exhibit a high treatment failure rate. Red flags are older age, comorbidities, neurologic deficits and local abscess formation. Whether these patients benefit from intensified treatment (e.g. radical surgery, prolongation of antibiotics) should be investigated further.


Assuntos
Bacteriemia , Osteomielite , Infecções Estafilocócicas , Idoso , Antibacterianos/uso terapêutico , Bacteriemia/tratamento farmacológico , Bacteriemia/epidemiologia , Humanos , Osteomielite/tratamento farmacológico , Osteomielite/epidemiologia , Estudos Prospectivos , Fatores de Risco , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/epidemiologia , Staphylococcus aureus , Falha de Tratamento
6.
Public Health Nutr ; 23(11): 1924-1930, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32646532

RESUMO

OBJECTIVE: To examine the impact of Nutrition for Life (NFL), a goal-setting nutrition education program, on the knowledge, self-efficacy and behaviour of adults eligible for Supplemental Nutrition Assistance Program-Education. DESIGN: NFL was developed using a 4-week goal-setting behavioural strategy focused on nutrition, physical activity and meal planning techniques. A quantitative repeated-measures design using self-reported data was collected at pre- and post-interventions and at 1-week and 1-month follow-ups. SETTING: Two Federally Qualified Health Centers in Philadelphia, PA, USA. PARTICIPANTS: A total of ninety-eight participants enrolled in the intervention; the majority were women (80·2 %), Black/Non-Hispanic (75·0 %) and 45-54 year old (39·6 %). RESULTS: Participants showed significant improvement in knowledge, self-efficacy and behaviour. Specifically, mean daily intake for vegetables increased by 0·31 cup (P < 0·05) and for fruits by 0·39 cup (P < 0·01) at 1-week follow-up. Participants also showed healthier behaviour at 1-month follow-up. Planning at least seven meals per week increased from 14·8 to 50 % (P < 0·01), completing at least 30 min of physical activity every day in the last week increased from 16·7 to 36 % (P < 0·01) and consuming water with all meals increased from 39 to 70·6 % (P < 0·01). CONCLUSIONS: The implementation of a goal-oriented nutrition education program offers a promising approach at achieving positive behaviour change among SNAP-eligible adults.


Assuntos
Dieta Saudável/psicologia , Comportamento Alimentar/psicologia , Assistência Alimentar , Objetivos , Promoção da Saúde/métodos , Adulto , Dieta Saudável/métodos , Exercício Físico/psicologia , Feminino , Comportamentos Relacionados com a Saúde , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , Planejamento de Cardápio/métodos , Pessoa de Meia-Idade , Philadelphia , Avaliação de Programas e Projetos de Saúde , Autoeficácia
7.
Ann Oncol ; 31(3): 422-429, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32067684

RESUMO

BACKGROUND: Long-term survival of high-risk neuroblastoma patients is still below 50% despite intensive multimodal treatment. This trial aimed to address whether the addition of two topotecan-containing chemotherapy courses compared to standard induction therapy improves event-free survival (EFS) of these patients. PATIENTS AND METHODS: An open-label, multicenter, prospective randomized controlled trial was carried out at 58 hospitals in Germany and Switzerland. Patients aged 1-21 years with stage 4 neuroblastoma and patients aged 6 months to 21 years with MYCN-amplified tumors were eligible. The primary endpoint was EFS. Patients were randomly assigned to standard induction therapy with six chemotherapy courses or to experimental induction chemotherapy starting with two additional courses of topotecan, cyclophosphamide, and etoposide followed by standard induction chemotherapy (eight courses in total). After induction chemotherapy, all patients received high-dose chemotherapy with autologous hematopoietic stem cell rescue and isotretinoin for consolidation. Radiotherapy was applied to patients with active tumors at the end of induction chemotherapy. RESULTS: Of 536 patients enrolled in the trial, 422 were randomly assigned to the control arm (n = 211) and the experimental arm (n = 211); the median follow-up time was 3.32 years (interquartile range 1.65-5.92). At data lock, the 3-year EFS of experimental and control patients was 34% and 32% [95% confidence Interval (CI) 28% to 40% and 26% to 38%; P = 0.258], respectively. Similarly, the 3-year overall survival of the patients did not differ [54% and 48% (95% CI 46% to 62% and 40% to 56%), respectively; P = 0.558]. The response to induction chemotherapy was not different between the arms. The median number of non-fatal toxicities per patient was higher in the experimental group while the median number of toxicities per chemotherapy course was not different. CONCLUSION: While the burden for the patients was increased by prolonging the induction chemotherapy and the toxicity, the addition of two topotecan-containing chemotherapy courses did not improve the EFS of high-risk neuroblastoma patients and thus cannot be recommended. CLINICAL TRIALS. GOV NUMBER: NCT number 03042429.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Quimioterapia de Indução , Neuroblastoma , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Criança , Pré-Escolar , Intervalo Livre de Doença , Alemanha , Humanos , Lactente , Neuroblastoma/tratamento farmacológico , Estudos Prospectivos , Suíça , Resultado do Tratamento , Adulto Jovem
8.
Eur Arch Otorhinolaryngol ; 277(1): 31-35, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31552525

RESUMO

PURPOSE: It is important for the surgeon to determine the position of the CI electrode array during and after its placement within the cochlea. Most preferably, this should be within the scala tympani to obtain the best audiological outcome. Thus, misplacement into the scala vestibuli or tip fold-over should be prevented. Since there are different ways to ensure proper positioning of the electrode array within the scala tympani (e.g., intraoperative radiography, electrophysiological recordings), our study was aimed at detecting intraoperative electrophysiologic characteristics to better understand the mechanisms of those electrode tip fold-overs. MATERIAL AND METHODS: In a multi-centric, retrospective case-control series, patients with a postoperatively by radiography detected tip fold-over in perimodiolar electrodes were included. The point of fold-over (i.e., the electrode position) was determined and the intraoperative Auto-NRT recordings were analysed and evaluated. RESULTS: Four patients were found to have an electrode tip fold-over (out of 85 implantees). Significant changes of the Auto-NRT recordings were not detected. All tip fold-overs occurred in the most apical part of the electrodes. DISCUSSION: Cochlear implantation for hearing impaired patients plays a decisive role in modern auditory rehabilitation. Perimodiolar electrode arrays may fold over during the insertion and, hence, could have a negative impact on audiological outcome. Characteristic electrophysiologic changes to possibly predict this were not found in our series.


Assuntos
Implante Coclear/efeitos adversos , Implantes Cocleares/efeitos adversos , Técnicas de Diagnóstico Otológico , Eletrodiagnóstico/métodos , Perda Auditiva Neurossensorial/cirurgia , Rampa do Tímpano/cirurgia , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
9.
J Pediatr Urol ; 15(1): 62.e1-62.e7, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30482497

RESUMO

PURPOSE: The ventral aspect of the penis in boys with hypospadias is composed of dysplastic tissue of the skin and the urethra. The aim of this study was to assess the pre-operative size and biomechanical properties of urethrae in boys with and without hypospadias using a more objective catheter-based system. MATERIALS & METHODS: In this non-blinded clinical observation study, the study population consisted of 19 boys with hypospadias-the case group (median age 13.9 months [range: 12.2-21.3])-and seven boys without hypospadias-the control group (median age 8.5 months [range: 3.8-18.1]). Modified measurements of impedance were used to assess the size, compliance and viscoelasticity of the urethrae under stepwise increased pressures (between 0, 40 and 60 cmH2O) using a customised Endolumenal Functional Lumen Imaging probe (EndoFLIP®). RESULTS: The sizes of the urethrae in boys with hypospadias are variable but tend towards being narrower and less compliant than those of the control subjects i.e. median diameter for meatus urethra was 3.2 mm (range: 2.98-3.92) in the hypospadias group compared with 3.64 (range: 3.22-4.44) in the control group at 40 cmH2O, and the median change in diameter at meatus urethra was 0.08 mm (range: -0.02 to 0.52) in the hypospadias group compared with 0.23 mm (range: -0.02 to 0.34) when the pressure was increased from 40 to 60 cmH2O. This biomechanical analysis found that there was no significant viscoelasticity of the urethral meatus in both the groups, whereas the remainder of the urethral structure generally had viscoelastic properties in the control group, seen as a creep on the time/diameter curves (Figure). In the group of boys with hypospadias, evaluations of the urethrae revealed varying viscoelastic abilities, ranging from abilities that were comparable with those of the control subjects to no sign of viscoelasticity at all. CONCLUSIONS: This study is the first to measure the biomechanical properties of the urethra in children, which might help to provide an understanding as to the structural and functional changes associated with hypospadias. The urethrae in the subjects with hypospadias were variable in diameter but tended to be narrower overall, especially in the distal portion of the urethra. Furthermore, the urethrae in boys with hypospadias were frequently less viscoelastic than those of controls. CLINICAL RELEVANCE: The EndoFLIP® system may be a future way of objectively estimating the severity of a urethral obstruction and could potentially be included in the postoperative assessment of patients with signs of hampered voiding.


Assuntos
Hipospadia/fisiopatologia , Uretra/fisiopatologia , Fenômenos Biomecânicos , Humanos , Lactente , Masculino
10.
J Laryngol Otol ; 132(3): 224-229, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29103379

RESUMO

BACKGROUND: Preservation of residual hearing is one of the major goals in modern cochlear implant surgery. Intra-cochlear fluid pressure changes influence residual hearing, and should be kept low before, during and after cochlear implant insertion. METHODS: Experiments were performed in an artificial cochlear model. A pressure sensor was inserted in the apical part. Five insertions were performed on two electrode arrays. Each insertion was divided into three parts, and statistically evaluated in terms of pressure peak frequency and pressure peak amplitude. RESULTS: The peak frequency over each third part of the electrode increased in both electrode arrays. A slight increase was seen in peak amplitude in the lateral wall electrode array, but not in the midscalar electrode array. Significant differences were found in the first third of both electrode arrays. CONCLUSION: The midscalar and lateral wall electrode arrays have different intra-cochlear fluid pressure changes associated with intra-cochlear placement, electrode characteristics and insertion.


Assuntos
Cóclea , Implantes Cocleares , Surdez/cirurgia , Eletrodos Implantados , Desenho de Equipamento , Pressão , Implante Coclear , Humanos , Modelos Biológicos
11.
Breast Cancer Res ; 19(1): 125, 2017 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-29183390

RESUMO

BACKGROUND: Controversies exist as to whether the genetic polymorphisms of the enzymes responsible for the metabolism of tamoxifen can predict breast cancer outcome in patients using adjuvant tamoxifen. Direct measurement of concentrations of active tamoxifen metabolites in serum may be a more biological plausible and robust approach. We have investigated the association between CYP2D6 genotypes, serum concentrations of active tamoxifen metabolites, and long-term outcome in tamoxifen treated breast cancer patients. METHODS: From an original observational study comprising 817 breast cancer patients, 99 women with operable breast cancer were retrospectively included in the present study. This cohort of patients were adjuvantly treated with tamoxifen, had provided serum samples suitable for measuring tamoxifen metabolites, and were relapse-free at 3 years after the primary treatment commenced. The median follow-up time from this entry point to breast cancer death was 13.9 years. Patients were CYP2D6 genotyped and grouped into four CYP2D6 phenotype groups (Ultra rapid, extensive, intermediate, and poor metabolizers). Tamoxifen and nine metabolites were quantified in serum (n = 86) and compared with CYP2D6 phenotype groups and outcome. RESULTS: Breast cancer patients with low concentrations of Z-4-hydroxy-tamoxifen (Z-4OHtam; ≤ 3.26 nM) had a breast cancer-specific survival (BCSS) of 60% compared to 84% in patients with Z-4OHtam concentrations > 3.26 nM (p = 0.020, log-rank hazard ratio (HR) = 3.56, 95% confidence interval (CI) = 1.14-11.07). For patients with Z-4-hydroxy-N-desmethyl-tamoxifen (Z-endoxifen) levels ≤ 9.00 nM BCSS was 57% compared to 84% for patients with concentrations > 9.00 nM (p = 0.029, HR = 3.73, 95% CI = 1.05-13.22). Low concentrations of Z-4OHtam and Z-endoxifen were associated with poorer survival also after adjusting for clinically relevant variables (HR = 4.27, 95% CI = 1.35-13.58, and HR = 3.70, 95% CI = 1.03-13.25, respectively). Overall survival analysis showed similar survival differences for both active metabolites. The Antiestrogen Activity Score showed comparable effects, but did not improve the prognostic information. CONCLUSIONS: Patients with Z-4OHtam and Z-endoxifen concentrations lower than 3.26 nM or 9.00 nM, respectively, showed an adverse outcome. Our results suggest that direct measurement of active tamoxifen metabolite concentrations could be of clinical value. Validation in larger study cohorts is warranted.


Assuntos
Antineoplásicos Hormonais/farmacocinética , Neoplasias da Mama/sangue , Neoplasias da Mama/mortalidade , Tamoxifeno/farmacocinética , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Quimioterapia Adjuvante , Citocromo P-450 CYP2D6/genética , Citocromo P-450 CYP2D6/metabolismo , Feminino , Humanos , Pessoa de Meia-Idade , Gradação de Tumores , Variantes Farmacogenômicos , Prognóstico , Estudos Retrospectivos , Tamoxifeno/uso terapêutico
13.
Leukemia ; 31(10): 2048-2056, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28196983

RESUMO

Recent developments in sequencing technologies led to the discovery of a novel form of genomic instability, termed chromothripsis. This catastrophic genomic event, involved in tumorigenesis, is characterized by tens to hundreds of simultaneously acquired locally clustered rearrangements on one chromosome. We hypothesized that leukemias developing in individuals with Ataxia Telangiectasia, who are born with two mutated copies of the ATM gene, an essential guardian of genome stability, would show a higher prevalence of chromothripsis due to the associated defect in DNA double-strand break repair. Using whole-genome sequencing, fluorescence in situ hybridization and RNA sequencing, we characterized the genomic landscape of Acute Lymphoblastic Leukemia (ALL) arising in patients with Ataxia Telangiectasia. We detected a high frequency of chromothriptic events in these tumors, specifically on acrocentric chromosomes, as compared with tumors from individuals with other types of DNA repair syndromes (27 cases total, 10 with Ataxia Telangiectasia). Our data suggest that the genomic landscape of Ataxia Telangiectasia ALL is clearly distinct from that of sporadic ALL. Mechanistically, short telomeres and compromised DNA damage response in cells of Ataxia Telangiectasia patients may be linked with frequent chromothripsis. Furthermore, we show that ATM loss is associated with increased chromothripsis prevalence in additional tumor entities.


Assuntos
Proteínas Mutadas de Ataxia Telangiectasia/fisiologia , Ataxia Telangiectasia/genética , Proteínas de Neoplasias/fisiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Adolescente , Ataxia Telangiectasia/complicações , Proteínas Mutadas de Ataxia Telangiectasia/deficiência , Proteínas Mutadas de Ataxia Telangiectasia/genética , Criança , Pré-Escolar , Cromossomos Humanos/ultraestrutura , Cromotripsia , Reparo do DNA/genética , DNA de Neoplasias/genética , Feminino , Genoma Humano , Instabilidade Genômica , Humanos , Hibridização in Situ Fluorescente , Masculino , Mutação , Proteínas de Neoplasias/deficiência , Proteínas de Neoplasias/genética , Neoplasias/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/etiologia , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , RNA Neoplásico/genética , Análise de Sequência de DNA , Análise de Sequência de RNA , Encurtamento do Telômero/genética , Transcriptoma
14.
HNO ; 65(Suppl 2): 81-86, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28116456

RESUMO

BACKGROUND: Assessment of the internal auditory canal (IAC) and cochlea is of central importance in neurotology. The artefacts and visibility of active auditory implants on magnetic resonance imaging (MRI) vary because of their specific magnetic components. Knowledge of the size of MRI artefacts and the options for handling them is important for the auditory rehabilitation of specific diseases (e. g., vestibular schwannoma). METHODS: The current article is a literature review. RESULTS: MRI assessment of the IAC and cochlea after surgical placement of an active auditory implant is feasible only with a percutaneous bone-anchored hearing aid (BAHA, Ponto). When specific factors (implant position and MRI sequence) are taken into consideration, these structures can be visualized even after cochlear implantation. Complications such as magnet dislocation and pain may occur. CONCLUSION: The possibility of assessing the IAC and cochlea by MRI is an important aspect that needs to be taken into consideration when planning the auditory rehabilitation of patients after acoustic neuroma surgery.


Assuntos
Cóclea/diagnóstico por imagem , Implantes Cocleares , Orelha Interna/diagnóstico por imagem , Imageamento por Ressonância Magnética , Complicações Pós-Operatórias/diagnóstico por imagem , Artefatos , Humanos , Neuroma Acústico/reabilitação
15.
Phys Rev Lett ; 119(26): 267201, 2017 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-29328716

RESUMO

Quantum confinement permits the existence of multiple terahertz magnon modes in atomically engineered ultrathin magnetic films and multilayers. By means of spin-polarized high-resolution electron energy-loss spectroscopy, we report on the direct experimental detection of all exchange-dominated terahertz confined magnon modes in a 3 ML Co film. We demonstrate that, by tuning the structural and magnetic properties of the Co film, through its epitaxial growth on different surfaces, e.g., Ir(001), Cu(001), and Pt(111), one can achieve entirely different in-plane magnon dispersions, characterized by positive and negative group velocities. Our first-principles calculations show that spin-dependent many-body correlation effects in Co films play an important role in the determination of the energies of confined magnon modes. Our results suggest a pathway towards the engineering of the group velocity of confined ultrafast magnons.

16.
HNO ; 65(9): 735-740, 2017 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-27921114

RESUMO

BACKGROUND: Assessment of the internal auditory canal (IAC) and the cochlea is of central importance in neurotology. The artefacts and visibility of the different types of active auditory implants in MRI vary, due to their specific ferromagnetic components. Knowledge of the size of MRI artefacts and the options for handling these is important for the auditory rehabilitation of specific diseases (e. g., vestibular schwannoma). METHODS: The current paper is a literature review RESULTS: MRI assessment of the IAC and cochlea after surgical placement of an active auditory implant is feasible only with a percutaneous bone-anchored hearing aid (BAHA, Ponto). When specific factors (implant position and MRI sequence) are taken into consideration, these structures can be visualized even after cochlear implantation. Complications such as magnet dislocation and pain may occur. CONCLUSION: The possibility of assessing the IAC and cochlea by MRI is an important aspect that needs to be taken into consideration when planning the auditory rehabilitation of patients after acoustic neuroma surgery.


Assuntos
Implante Coclear , Implantes Cocleares , Orelha Interna , Neuroma Acústico , Cóclea/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Neuroma Acústico/diagnóstico por imagem
17.
Eur Arch Otorhinolaryngol ; 273(12): 4251-4256, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27351885

RESUMO

The position of the cochlear electrode array within the scala tympani is essential for an optimal hearing benefit. An intraoperative NRT-ratio was established, which can provide information about the intraoperative intracochlear electrode array position for perimodiolar electrodes. The aims of this study were to verify the longterm reliability for the NRT-ratio in perimodiolar electrodes. In a retrospective controlled study in a Tertiary Referral Center the electrophysiological data sets of 123 patients with implanted Nucleus Contour Advance electrodes were enclosed. Intraoperative and up to 1 year follow-up Auto-NRTs were evaluated. A NRT-ratio was calculated by dividing the average Auto-NRT data from electrode 16 to 18 with the average from electrode 5 to 7. Using a flat panel tomography system, the position of the electrode array was certified radiological. 31 patients with perimodiolar electrodes with 1 year follow-up data were included in the study. Eleven patients showed regular follow-up NRT-ratio with a correlated and radiologically confirmed electrode position. 20 patients showed mismatches between the NRT-ratio and the radiological position. These patients were highly variable in terms of duration of deafness and neural spectrum disorders. The NRT-ratio can be used to determine the intracochlear position of the electrode array for perimodiolar electrodes. Intraoperatively the NRT-ratio predicts the array position within the cochlea highly reliable for perimodiolar electrodes. We showed that after 6 months and a year, the NRT-ratio remains unchanged in most of the cases and shows a good correlation to the radiological determined position of the array. Nevertheless, the condition of the neural structures is highly important for reproducible responses. Limited validity is given in patients with degenerative and structural neural disorders.


Assuntos
Implante Coclear/métodos , Implantes Cocleares , Eletrodos Implantados , Perda Auditiva Neurossensorial/reabilitação , Telemetria , Adulto , Cóclea/diagnóstico por imagem , Orelha Interna , Fenômenos Eletrofisiológicos , Feminino , Seguimentos , Perda Auditiva Neurossensorial/fisiopatologia , Testes Auditivos , Humanos , Período Intraoperatório , Masculino , Reprodutibilidade dos Testes , Estudos Retrospectivos , Janela da Cóclea , Rampa do Tímpano , Fatores de Tempo , Tomografia/métodos , Tomografia Computadorizada por Raios X
18.
Eur Arch Otorhinolaryngol ; 273(11): 3609-3613, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26993657

RESUMO

To preserve residual hearing in cochlear implant candidates, the atraumatic insertion of the cochlea electrode has become a focus of cochlea implant research. In a previous study, intracochlear pressure changes during the opening of the round window membrane were investigated. In the current study, intracochlear pressure changes during opening of the round window membrane under dry and transfluid conditions were investigated. Round window openings were performed in an artificial cochlear model. Intracochlear pressure changes were measured using a micro-optical pressure sensor, which was placed in the apex. Openings of the round window membrane were performed under dry and wet conditions using a cannula and a diode laser. Statistically significant differences in the intracochlear pressure changes were seen between the different methods used for opening of the round window membrane. Lower pressure changes were seen by opening the round window membrane with the diode laser than with the cannula. A significant difference was seen between the dry and wet conditions. The atraumatic approach to the cochlea is assumed to be essential for the preservation of residual hearing. Opening of the round window under wet conditions produce a significant advantage on intracochlear pressure changes in comparison to dry conditions by limiting negative outward pressure.


Assuntos
Cóclea/fisiologia , Implante Coclear/métodos , Pressão , Janela da Cóclea/cirurgia , Cânula , Implantes Cocleares , Humanos , Lasers , Modelos Biológicos
19.
Phys Rev Lett ; 116(5): 056802, 2016 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-26894727

RESUMO

In scanning tunneling microscopy, orbital selectivity of the tunneling process can make the topographic image dependent on a tip-surface distance. We have found reproducible dependence of the images on the distance for a monatomic layer of iron nitride formed on a Cu(001) surface. Observed atomic images systematically change between a regular dot array and a dimerized structure depending on the tip-surface distance, which turns out to be the only relevant parameter in the image variation. An accompanied change in the weight of Fe-3d local density of states to a tunneling background was detected in dI/dV spectra. These have been attributed to a shift in surface orbitals detected by the tip from the d states to the s/p states with increasing the tip-surface distance, consistent with an orbital assignment from first-principles calculations.

20.
HNO ; 64(3): 156-62, 2016 Mar.
Artigo em Alemão | MEDLINE | ID: mdl-26879879

RESUMO

BACKGROUND: Cochlear implants (CI) are the preferred method of treatment for patients with severe to profound bilateral sensorineural hearing loss and unilateral deafness. For many years, because of the magnetic field during magnetic resonance imaging (MRI) examinations, MRI examinations were contraindicated for CI patients or feasible only under specific circumstances. MRI examinations of CI recipients entail complications and therefore preventive measures have to be considered. The aim of this study was to evaluate the incidence of MRI scans in CI recipients and the occurrence of complications, and furthermore to investigate the preventive measures taken in radiological daily routine. MATERIALS AND METHODS: A retrospective questionnaire was sent to 482 patients that received CIs from 1999-2013. Details of the MRI examination and subjective and objective incidents during and after the MRI scan were evaluated. RESULTS: A total of 204 CI recipients answered the retrospective questionnaire (42.3%). Twenty patients (9.8%) with 23 implants underwent a total of 33 MRI scans with their cochlear implant in place. In 16 cases the scanned region was the head (49%). Preventive measures in the form of head bandages were taken in 20 cases (61%). The most common complication was pain in 23 cases (70%) and the most serious complication was the dislocation of the internal magnet in 3 cases (9%). CONCLUSIONS: The number of CI recipients undergoing MRI scans is quite high. Possible complications and preventive measures attract too little attention in radiological daily routine.


Assuntos
Implantes Cocleares/estatística & dados numéricos , Migração de Corpo Estranho/epidemiologia , Imageamento por Ressonância Magnética/estatística & dados numéricos , Dor/epidemiologia , Adolescente , Adulto , Idoso , Criança , Bandagens Compressivas/estatística & dados numéricos , Contraindicações , Feminino , Migração de Corpo Estranho/diagnóstico , Migração de Corpo Estranho/prevenção & controle , Alemanha/epidemiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Dor/diagnóstico , Dor/prevenção & controle , Proteção Radiológica/estatística & dados numéricos , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
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