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2.
Biosystems ; 201: 104331, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33358828

RESUMO

Cells associated with an abnormal (cancerous) growth exchange flows, morph freely and grow hand-in-glove with their immediate environment, the extracellular matrix (ECM). The cell structure experiences two mass flows in counterflow. Flowing into the structure are nutrients and flowing out is refuse from the metabolically active biomass within. The physical effect of the evolution of the cell and extracellular structure is more flow and mixing in that space, that is, more mixing than in the absence of a biological growth in that space. The objective of the present theory is to predict the increase in the size of the cell cluster as a function of its structure, and also to predict the critical cluster sizes that mark the transitions from one distinct cluster configuration to the next. This amounts to predicting the timing and the main features of the transitions from single cell to clusters with two, four, eight and more cells, including larger clusters with cells organized on its outer surface. The predicted evolution of the size and configuration of the cell cluster is validated successfully by comparison with measurements from several independent studies of cancerous and non-cancerous growth patterns.


Assuntos
Algoritmos , Carcinogênese/metabolismo , Proliferação de Células/fisiologia , Matriz Extracelular/fisiologia , Modelos Biológicos , Neoplasias/fisiopatologia , Animais , Carcinogênese/patologia , Tamanho Celular , Microambiente Celular/fisiologia , Matriz Extracelular/metabolismo , Humanos , Neoplasias/metabolismo , Neoplasias/patologia
3.
Radiat Oncol ; 15(1): 244, 2020 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-33099305

RESUMO

An amendment to this paper has been published and can be accessed via the original article.

4.
Radiat Oncol ; 15(1): 187, 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32736570

RESUMO

The growing acceptance and recognition of Surface Guided Radiation Therapy (SGRT) as a promising imaging technique has supported its recent spread in a large number of radiation oncology facilities. Although this technology is not new, many aspects of it have only recently been exploited. This review focuses on the latest SGRT developments, both in the field of general clinical applications and special techniques.SGRT has a wide range of applications, including patient positioning with real-time feedback, patient monitoring throughout the treatment fraction, and motion management (as beam-gating in free-breathing or deep-inspiration breath-hold). Special radiotherapy modalities such as accelerated partial breast irradiation, particle radiotherapy, and pediatrics are the most recent SGRT developments.The fact that SGRT is nowadays used at various body sites has resulted in the need to adapt SGRT workflows to each body site. Current SGRT applications range from traditional breast irradiation, to thoracic, abdominal, or pelvic tumor sites, and include intracranial localizations.Following the latest SGRT applications and their specifications/requirements, a stricter quality assurance program needs to be ensured. Recent publications highlight the need to adapt quality assurance to the radiotherapy equipment type, SGRT technology, anatomic treatment sites, and clinical workflows, which results in a complex and extensive set of tests.Moreover, this review gives an outlook on the leading research trends. In particular, the potential to use deformable surfaces as motion surrogates, to use SGRT to detect anatomical variations along the treatment course, and to help in the establishment of personalized patient treatment (optimized margins and motion management strategies) are increasingly important research topics. SGRT is also emerging in the field of patient safety and integrates measures to reduce common radiotherapeutic risk events (e.g. facial and treatment accessories recognition).This review covers the latest clinical practices of SGRT and provides an outlook on potential applications of this imaging technique. It is intended to provide guidance for new users during the implementation, while triggering experienced users to further explore SGRT applications.


Assuntos
Neoplasias/radioterapia , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia Guiada por Imagem/métodos , Radioterapia de Intensidade Modulada/métodos , Humanos , Neoplasias/diagnóstico por imagem , Neoplasias/patologia , Dosagem Radioterapêutica
5.
Eye (Lond) ; 32(2): 173-178, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29148529

RESUMO

Anterior segment ischemia (ASI) is a potentially serious but rare complication of strabismus surgery. Among several risk factors, ASI occurs after strabismus surgery because of the nature of the anterior segment circulation. Disinsertion of rectus muscles leads to a decrease in the blood supply to the various anterior segment structures. We report a series of retrospective and prospective studies performed by our group focused on determining the risk of anterior segment ischemia following strabismus surgery, diagnosis, and modifications to surgical techniques to minimize the impact on anterior segment circulation. We found a significant decrease in postoperative anterior segment blood flow when operating vertical rectus muscles. Plication procedures preserve anterior segment circulation, and modifications to the technique allow the performance of adjustable sutures. Small adjustable selective procedures that spare the ciliary vessels have been demonstrated to be effective in patients with vertical and torsional diplopia. Ciliary sparing augmented adjustable transposition surgery decreases the risk of anterior segment ischemia while allowing management of potential post-operative alignment complications. Finally, ocular coherence tomography angiography is a valuable quantitative and qualitative technique to evaluate anterior segment ischemia. Strabismus surgeons should be aware of the risks of anterior segment ischemia when operating vertical rectus muscles. Modifications to standard surgical techniques allow surgeons to perform complex strabismus surgery in patients at risk for anterior segment ischemia.


Assuntos
Segmento Anterior do Olho/irrigação sanguínea , Oftalmopatias , Isquemia , Músculos Oculomotores/cirurgia , Procedimentos Cirúrgicos Oftalmológicos , Estrabismo/cirurgia , Oftalmopatias/diagnóstico , Oftalmopatias/etiologia , Oftalmopatias/terapia , Humanos , Isquemia/diagnóstico , Isquemia/etiologia , Isquemia/prevenção & controle , Procedimentos Cirúrgicos Oftalmológicos/efeitos adversos , Procedimentos Cirúrgicos Oftalmológicos/métodos , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Estudos Prospectivos , Estudos Retrospectivos
6.
Leukemia ; 32(2): 510-519, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28663580

RESUMO

The concept of arming antibodies with bioactive payloads for a site-specific therapy of cancer has gained considerable interest in recent years. However, a successful antibody-based targeting approach critically relies on the availability of a tumor-associated target that is not only preferentially expressed in the tumor tissue but is also easily accessible for antibody therapeutics coming from the bloodstream. Here, we perfused the vasculature of healthy and acute myeloid leukemia (AML)-bearing rats with a reactive ester derivative of biotin and subsequently quantified the biotinylated proteins to identify AML-associated bone marrow (BM) antigens accessible from the bloodstream. In total, >1400 proteins were identified. Overall, 181 proteins were >100-fold overexpressed in AML as compared with normal BM. Eleven of the most differentially expressed proteins were further validated by immunohistochemistry and confocal microscopic analyses, including novel antigens highly expressed in AML cells (for example, adaptor-related protein complex 3 ß2) and in the leukemia-modified extracellular matrix (ECM) (for example, collagen-VI-α-1). The presented atlas of targetable AML-associated BM proteins provides a valuable basis for the development of monoclonal antibodies that could be used as carriers for a site-specific pharmacodelivery of cytotoxic drugs, cytokines or radionuclides to the BM in AML.


Assuntos
Anticorpos Monoclonais/farmacologia , Medula Óssea/metabolismo , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/metabolismo , Animais , Medula Óssea/efeitos dos fármacos , Citocinas/metabolismo , Humanos , Imuno-Histoquímica/métodos , Masculino , Ratos , Ratos Endogâmicos BN
7.
Int J Tuberc Lung Dis ; 21(11): 1201-1205, 2017 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-29037303

RESUMO

SETTING AND OBJECTIVE: The International Study of Asthma and Allergies in Childhood (ISAAC) reported asthma prevalence in Peru to be among the highest in the world. We assessed the prevalence and morbidity of self-reported asthma in an underserved, peri-urban area of Lima, Peru, with limited medical access. DESIGN: The study was conducted in the outskirts of Lima from March to May 2011. Five hundred children aged 6-18 years were selected through cluster sampling. Parents completed a modified version of the ISAAC questionnaire. Children underwent spirometry testing. Those with a forced expiratory volume in one second (FEV1% predicted) 80% were tested for reversibility using salbutamol. RESULTS: Of the 500 children selected, 71% participated. The prevalence of asthma was 16.7%. Asthma symptoms were associated with self-reported asthma (P < 0.001); 52.5% of children with asthma had ever used an inhaler (P < 0.001), and 27.1% had never been to the doctor for respiratory problems (P < 0.001). CONCLUSION: We found a high prevalence of self-reported asthma and high morbidity related to asthma symptoms in the previous 12 months among the study cohort. Symptoms were poorly controlled due to limited availability of medication and access to medical services.


Assuntos
Asma/epidemiologia , Acessibilidade aos Serviços de Saúde , Estudantes/estatística & dados numéricos , Adolescente , Asma/diagnóstico , Criança , Estudos de Coortes , Feminino , Volume Expiratório Forçado , Humanos , Masculino , Pais , Peru/epidemiologia , Prevalência , Autorrelato , Espirometria , Inquéritos e Questionários , População Urbana
9.
Bone Marrow Transplant ; 51(11): 1441-1448, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27295269

RESUMO

Allogeneic stem cell transplantation (SCT) remains the best curative option for patients with refractory AML or with high-risk myelodysplastic syndrome (MDS). For decades, age alone had been widely used as the primary criterion to assess eligibility for allogeneic SCT; however, prospective studies to evaluate allogeneic SCT in elderly patients are still limited. A total of 187 patients (median age of 64 years, range 60-77 years) with AML (87%) or MDS (13%) transplanted between 1999 and 2014 were included in this retrospective analysis. Relapse-free survival (RFS) and overall survival (OS) at 3 years were 32% (95% confidence interval (CI): 25-39%) and 35% (95%CI: 27-42%), respectively. Overall survival was 49% (95%CI: 35-64%) in AML patients who were transplanted in first complete remission (CR1), but even patients with active disease did benefit from transplantation, showing an OS at 3 years of 30% (95%CI: 20-40%). Multivariate analysis revealed disease- and patient-specific risk indices as independent prognostic factors for OS and non-relapse mortality (NRM). In conclusion, our monocenter results indicate that patients should not be generally withheld from allogeneic SCT because of age or disease status only. Specific risk models incorporating disease status and disease-specific risk factors at the time of transplantation as well as existing comorbidities are helpful tools to assess transplantation-associated risk factors of elderly patients.


Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Leucemia Mieloide Aguda/terapia , Síndromes Mielodisplásicas/terapia , Medição de Risco/métodos , Fatores Etários , Idoso , Feminino , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Leucemia Mieloide Aguda/mortalidade , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/mortalidade , Estudos Retrospectivos , Análise de Sobrevida , Transplante Homólogo , Resultado do Tratamento
10.
Eur J Neurol ; 23(1): 13-20, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26492944

RESUMO

BACKGROUND AND PURPOSE: In Europe intravenous thrombolysis (IVT) for ischaemic stroke is still not approved for patients aged >80 years. However, elderly patients are frequently treated based on individual decision making. In a retrospective observational study a consecutive and prospective stroke registry in southwest Germany was analysed. METHODS: The data registry collected 101,349 patients with ischaemic stroke hospitalized from January 2008 to December 2012. Of these, 38,575 (38%) were aged 80 years and older and 10 286 (10.1%) underwent IVT. Favourable outcome at discharge was defined as modified Rankin Scale (mRS) ≤1 or not worse than prior to stroke. Multiple logistic regression models stratified by 10-year age groups were used to assess the relationship between IVT and mRS at discharge, adjusted for patient characteristics, admitting facility and length of hospital stay. RESULTS: The highest IVT rate was 15% in patients aged <50 years, with a continuous decline down to 8% in patients aged ≥90 years. Adjusted odds ratios and 95% confidence intervals for patients 80-89 years of age were 2.20 (1.95-2.47) (P < 0.0001) and 1.25 (0.88-1.78) (P = 0.21) for patients >90 years of age, compared to patients of the same age decade not treated with IVT. CONCLUSIONS: The evidence from routine hospital care in southwest Germany indicates that IVT is an effective treatment also for aged patients with ischaemic stroke in an age range between 80 and 89 years. Although no clear evidence for the effectiveness of IVT beyond 90 years was found, treatment should also be carefully considered in these patients. High age should not discourage from treatment.


Assuntos
Isquemia Encefálica/tratamento farmacológico , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Sistema de Registros , Acidente Vascular Cerebral/tratamento farmacológico , Terapia Trombolítica/estatística & dados numéricos , Administração Intravenosa , Idoso , Idoso de 80 Anos ou mais , Feminino , Alemanha/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
11.
Bone Marrow Transplant ; 50(4): 485-92, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25599163

RESUMO

Non-relapse mortality after Allo-SCT has significantly decreased over the last years. Nevertheless, relapse remains a major cause for post SCT mortality in patients with AML and high-risk myelodysplastic syndrome (MDS). In this retrospective single-center analysis, we have analyzed the treatment outcomes of 108 patients with AML or MDS, who relapsed after Allo-SCT. Seventy of these patients (65%) were treated with salvage therapies containing chemotherapy alone, allogeneic cell-based treatment or the combination of both. Thirty-eight patients (35%) received palliative treatment. Median OS after diagnosis of relapse was 130 days. Compared with patients who received chemotherapy alone, response to salvage therapy was significantly improved in patients treated with a combination of chemo- and allogeneic cell-based therapy (CR rate 57% vs 13%, P=0.002). Among risk factors concerning pretreatment characteristics, disease status before first Allo-SCT, and details of transplantation, only the time interval from Allo-SCT to relapse was an independent predictor of response to salvage therapy and OS. These data confirmed that time to relapse after transplantation is an important prognostic factor. Up to now, only patients eligible for treatment regimens containing allogeneic cell-based interventions achieved relevant response rates.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/terapia , Síndromes Mielodisplásicas/mortalidade , Síndromes Mielodisplásicas/terapia , Terapia de Salvação , Adolescente , Adulto , Idoso , Aloenxertos , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Taxa de Sobrevida , Fatores de Tempo
12.
Strahlenther Onkol ; 189(6): 486-94, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23636349

RESUMO

PURPOSE: To report on chronic adverse events (CAE) and quality of life (QOL) after radiochemotherapy (RCT) in patients with anal cancer (AC). PATIENTS AND METHODS: Of 83 patients who had received RCT at our department between 1988 and 2011, 51 accepted the invitation to participate in this QOL study. CAE were evaluated using the Common Terminology Criteria for Adverse Events (CTCAE) v. 4.0 and QOL was assessed with the Functional Assessment of Cancer Therapy-Colorectal (FACT-C) questionnaire. RESULTS: CAE could be evaluated in 49 patients. There was a tendency toward a higher rate of grade 3 CAE in female patients, i.e. 18 out of 37 (49 %) vs. 2 out of 12 (17 %) male patients (p = 0.089). The most common grade 3 CAE were dyspareunia and vaginal symptoms (itching, burning and dryness) in 35 and 22 % of female patients, respectively, followed by stool incontinence in 13 % of all patients (6 out of 49). Both FACT-C and CAE information were available for 42 patients, allowing evaluation of the impact of CAE on QOL. The median total FACT-C score was 110 (40-132) out of a possible maximum of 136. The absence of grade 3 CAE (115 vs. 94, p = 0.001); an interval of ≥ 67 months after the end of the treatment (111 vs. 107, p = 0.010), no stool incontinence vs. grade 3 stool incontinence (111 vs. 74, p = 0.009), higher education (114 vs. 107, p = 0.013) and no dyspareunia vs. grade 3 dyspareunia (116 vs. 93, p = 0.012) were significantly associated with a higher median FACT-C score. CONCLUSION: The majority of AC patients treated with RCT have acceptable overall QOL scores, which are comparable to those of the normal population. Patients with grade 3 CAE-particularly dyspareunia and fecal incontinence-have a poorer QOL compared to patients without CAE. In order to improve long-term QOL, future strategies might aim at a reduction in dose to the genitalia and more intensive patient support measures.


Assuntos
Neoplasias do Ânus/terapia , Quimiorradioterapia/efeitos adversos , Qualidade de Vida/psicologia , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Ânus/patologia , Quimiorradioterapia/métodos , Quimiorradioterapia/psicologia , Dispareunia/etiologia , Incontinência Fecal/etiologia , Feminino , Seguimentos , Alemanha , Humanos , Masculino , Pessoa de Meia-Idade , Lesões por Radiação/etiologia , Reto/efeitos da radiação , Sistema Urogenital/efeitos da radiação , Vagina/efeitos da radiação
13.
Eur J Neurol ; 20(5): 812-7, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23293855

RESUMO

BACKGROUND AND PURPOSE: The ASCO score has the advantage of allowing a more comprehensive characterization of ischaemic stroke patients and their risk factors, as reflected in different grades of evidence of atherosclerotic changes (A), small vessel disease (S), potential cardiac (C) or other (O) sources. It might also help to characterize patients with recurrent ischaemic stroke and document the etiology of stroke recurrence as well as the further development of risk factor constellations. METHODS: We prospectively screened our stroke database for patients with recurrent ischaemic stroke between 2004 and 2011, and classified each stroke using ASCO. The distribution of etiologies was analysed, and changes in the ASCO score were documented for each patient. RESULTS: We identified 131 patients with recurrence of ischaemic stroke. At the first event, the distribution of etiologies and their grade of evidence was 97 grade 1 (A = 18/S = 32/C = 44/O = 3), six grade 2 (A = 2/S = 1/C = 3/O = 0), 199 grade 3 (A = 85/S = 83/C = 23/O = 8), 204 grade 0 (A = 26/S = 14/C = 44/O = 120) and 18 grade 9 (A = 0/S = 1/C = 17/O = 0). At stroke recurrence, 98 grade 1 (A = 16/S = 24/C = 55/O = 3), 11 grade 2 (A = 2/S = 5/C = 4/O = 0), 210 grade 3 (A = 94/S = 92/C = 13/O = 11), 171 grade 0 (A = 16/S = 9/C = 26/O = 117) and 34 grade 9 (A = 0/S = 1/C = 33/O = 0) were identified. Analysis of each individual showed a modification of the score in 85 patients (64.9%). CONCLUSIONS: Recurrent ischaemic stroke does not always have the same etiology as the previous one(s). Among variable changes of grade 1 etiologies, an increasing prevalence of cardioembolism--often insufficiently treated--at stroke recurrence was a major finding. ASCO proved to be highly useful to monitor risk factor constellations.


Assuntos
Isquemia Encefálica/diagnóstico , Isquemia Encefálica/etiologia , Índice de Gravidade de Doença , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Isquemia Encefálica/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Fatores de Risco , Acidente Vascular Cerebral/complicações
14.
Strahlenther Onkol ; 189(1): 18-25, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23149618

RESUMO

PURPOSE: To report the efficacy and toxicity of radio(chemo)therapy (RCT) in the management of squamous cell anal carcinoma (SQ-AC) and to evaluate the prognostic factors influencing the outcomes. PATIENTS AND METHODS: A consecutive cohort of 138 patients with cT1-4, cN0-3, cM0 SQ-AC were treated with RCT between 1988 and 2011 at our department. Median follow-up time for surviving patients from the start of RCT was 98 months (range, 1-236 months). Patients were treated with a median radiation dose of 56 Gy (range, 4-61 Gy). Concurrent chemotherapy was administered to 119 patients (86%). RESULTS: The survival rates at 2, 5, and 10 years were 88 ± 3, 82 ± 4, and 59 ± 6%, respectively, with a median overall survival (OS) of 167 months. The cumulative incidence for local recurrence at 2 and 5 years was 8 ± 2 and 11 ± 3%, respectively. The median disease-free survival (DFS) and colostomy-free survival (CFS) times were 132 and 135 months, respectively. In 19 patients (14%), a distant metastasis was diagnosed after a median time of 19 months. In the multivariate analysis, UICC (International Union Against Cancer) stage I-II, female gender, Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, and good/moderate histologic differentiation (G1-2) were significantly associated with a better OS, DFS, and CFS. Conformal radiotherapy planning techniques were significantly associated with a lower cumulative incidence of local recurrence (11 ± 3% vs. 38 ± 19% at 5 years, p = 0.006). A higher radiation dose beyond 54 Gy was not associated with an improvement in outcome, neither for smaller-(T1/T2) nor for larger tumors (T3/T4). CONCLUSION: RCT leads to excellent outcomes-especially in patients with stage I/II and G1/G2 tumors-with acceptable toxicity. The probable advantages of high-dose radiotherapy should be considered carefully against the risk of a higher rate of toxicity. Future studies are needed to investigate the role of a more intensified (systemic) treatment for patients with unfavorable prognostic factors such as T3/T4, N+, and/or poor cell differentiation.


Assuntos
Neoplasias do Ânus/tratamento farmacológico , Neoplasias do Ânus/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Ânus/mortalidade , Neoplasias do Ânus/patologia , Quimioterapia Adjuvante , Colonoscopia , Terapia Combinada , Progressão da Doença , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/radioterapia , Estadiamento de Neoplasias , Prognóstico , Radioterapia/métodos , Dosagem Radioterapêutica , Fatores Sexuais
15.
J Neurol ; 259(9): 1951-7, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22349872

RESUMO

Multiple acute ischemic lesions in different hemispheres or vascular territories are mainly considered to be of proximal embolic origin. However, despite careful diagnostic work-up, the etiological classification often stays undetermined. We propose that multiple acute ischemic lesions can sometimes be a phenomenon observed in small vessel disease (SVD). From a prospectively collected database of more than 7,000 stroke patients, 173 patients with acute bihemispheric infarction were identified. We analyzed those subjects with multiple small (< 15 mm Ø) subcortical acute ischemic lesions on diffusion-weighted MRI (DWI) and concomitant severe small vessel disease (Fazekas grades II-III) without a proximal embolic source as evaluated by cardiological investigations. Twenty patients (mean age 66 ± 12 years, 12 men) with a mean number of 2.95 ± 1.24 acute lesions on DWI (range of 2-7 lesions per patient) were identified (n = 5 Fazekas II°, n = 15 Fazekas III°). Most of the lesions were located in typical areas of lacunar infarction. The mean NIHSS score on admission was 2.95 ± 2.0 (range 0-8). Multiple acute ischemic lesions in different vascular territories might not always be of proximal cardiovascular embolic origin. Simultaneous small subcortical ischemic lesions may reflect remote ischemia due to small vessel disease reflecting simultaneous hemorheological dysfunction.


Assuntos
Vasos Sanguíneos/patologia , Isquemia Encefálica/complicações , Isquemia Encefálica/etiologia , Infarto Cerebral/etiologia , Embolia/complicações , Idoso , Idoso de 80 Anos ou mais , Imagem de Difusão por Ressonância Magnética , Feminino , Seguimentos , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco
16.
J Neurol ; 259(7): 1284-9, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22146904

RESUMO

Precise analysis of stroke subtypes is important for clinical treatment decisions, the prognostic evaluation of patients, as well as defining stroke populations in clinical studies. The TOAST classification is the most widely used and approved form for etiologic subtyping. Increasing knowledge about stroke mechanisms and the introduction of new diagnostic techniques have supported the promotion of the new ASCO phenotypic classification, which aims to characterize patients using different grades of evidence for stroke subtypes. We prospectively assigned 103 consecutive patients from our stroke center for subtype classification using ASCO and TOAST. Clinical features and complementary investigations were recorded according to our standardized acute stroke care protocol. Evidence grade 1 with ASCO was assessed in 12.62% for large artery disease (A), 23.30% small-vessel disease (S), 36.89% cardiac source (C) and 1.94% another cause (O). Evidence grades 1-3 were identified in 60.19% A, 75.73% S, 49.51% C, and 3.88% O. A total of 68.93% of the patients were classified in more than one category, and only 3.88% remained completely undetermined. The κ value for inter-rater agreement was 0.92-1. Using TOAST, the distribution was 9.71% A, 23.30% S, 34.95% C, 1.94% O, and 30.10% undetermined. The ASCO classification showed a good concordance with TOAST. The inter-rater agreement was high. The comprehensive character of ASCO allows the recording of important additional information. This may be helpful for a specific treatment adaptation in each individual patient and creation of different etiological profiles in view of adapted clinical trials.


Assuntos
Isquemia Encefálica , Acidente Vascular Cerebral , Doenças Vasculares , Adulto , Idoso , Idoso de 80 Anos ou mais , Isquemia Encefálica/classificação , Isquemia Encefálica/complicações , Isquemia Encefálica/diagnóstico , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Estudos Prospectivos , Reprodutibilidade dos Testes , Fatores de Risco , Índice de Gravidade de Doença , Acidente Vascular Cerebral/classificação , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/etiologia , Doenças Vasculares/classificação , Doenças Vasculares/complicações , Doenças Vasculares/diagnóstico , Adulto Jovem
17.
J Theor Biol ; 279(1): 29-43, 2011 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-21439301

RESUMO

In a previous paper we introduced a method called augmented sparse reconstruction (ASR) that identifies links among nodes of ordinary differential equation networks, given a small set of observed trajectories with various initial conditions. The main purpose of that technique was to reconstruct intracellular protein signaling networks. In this paper we show that a recursive augmented sparse reconstruction generates artificial networks that are homologous to a large, reference network, in the sense that kinase inhibition of several reactions in the network alters the trajectories of a sizable number of proteins in comparable ways for reference and reconstructed networks. We show this result using a large in-silico model of the epidermal growth factor receptor (EGF-R) driven signaling cascade to generate the data used in the reconstruction algorithm. The most significant consequence of this observed homology is that a nearly optimal combinatorial dosage of kinase inhibitors can be inferred, for many nodes, from the reconstructed network, a result potentially useful for a variety of applications in personalized medicine.


Assuntos
Proteínas/metabolismo , Transdução de Sinais , Algoritmos , Inibidores de Proteínas Quinases/metabolismo , Padrões de Referência
18.
Cytopathology ; 21(2): 86-92, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21054822

RESUMO

A European Federation of Cytology Societies (EFCS) working party of 28 members from 14 European countries met at the European Congress of Cytology in Lisbon in September 2009, with two observers from the USA, to discuss the need for standardising thyroid FNA nomenclature in the light of the National Institute of Cancer (NCI) recommendations resulting from the State of the Science conference in Bethesda in 2007. The data were obtained through two questionnaires sent by email and a transcript of the live discussion at the congress, which is presented in full. The surveys and discussion showed that there were currently no national terminologies for reporting thyroid FNA in the different European countries except in Italy and the UK. Personal, 'local', surgical pathology and descriptive terminologies were in use. All but one of the working party members agreed that thyroid FNA reporting should be standardised. Whilst almost a third would adopt the NCI Bethesda terminology, which offers the advantages of a 'risk of cancer' correlation and is linked to clinical recommendations, more than half favoured a translation of local terminology as the first step towards a unified nomenclature, as has been done recently in the UK. There was some disagreement about the use of: a) the six-tiered as opposed to four or five-tiered systems, b) the use of an indeterminate category and c) the 'follicular neoplasm' category, which was felt by some participants not to be different from the 'suspicious of malignancy' category. The conclusions will be passed to the different national societies of cytology for discussion, who will be asked to map their local terminologies to the Bethesda classification, observe its acceptance by clinicians and audit its correlation with outcome.


Assuntos
Biópsia por Agulha Fina , Doenças da Glândula Tireoide/patologia , Glândula Tireoide/patologia , Biópsia por Agulha Fina/métodos , Biópsia por Agulha Fina/normas , Europa (Continente) , Humanos , Guias de Prática Clínica como Assunto , Terminologia como Assunto
19.
Cytopathology ; 21(3): 147-56, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20482722

RESUMO

This report of the Editorial Advisory Board of Cytopathology gives the results of a survey of medical practitioners in cytopathology, which aimed to find out their views on the current situation in undergraduate and postgraduate training in their institutions and countries. The results show that training in cytopathology and histopathology are largely carried out at postgraduate level and tend to be organized nationally rather than locally. Histopathology was regarded as essential for training in cytopathology by 89.5% of respondents and was mandatory according to 83.1%. Mandatory cytopathology sections of histopathology were reported by 67.3% and specific examinations in cytopathology by 55.4%. The main deficiencies in training were due to its variability; there were insufficient numbers of pathologists interested in cytology and a consequent lack of training to a high level of competence. Pathologists without specific training in cytopathology signed out cytology reports according to 54.7% of responses, more often in centres where training was 3-6 months or less duration. Although 92.2% of respondents thought that specialist cytology should not be reported by pathologists without experience in general cytopathology, that practice was reported by 30.9%, more often in centres with small workloads. The survey report recommends that 6-12 months should be dedicated to cytopathology during histopathology training, with optional additional training for those wanting to carry out independent practice in cytopathology. Formal accreditation should be mandatory for independent practice in cytopathology. When necessary, temporary placements to centres of good practice should be available for trainees intending to practise independently in cytopathology. There should be adequate numbers of pathologists trained in cytopathology to a high level of competence; some of their time could be released by training cytotechnologists and trainee pathologists to prescreen cytology slides and assess adequacy of fine-needle aspiration samples when immediate diagnosis was not required. The survey demonstrated a clear need for European and international guidelines for training in cytopathology.


Assuntos
Citodiagnóstico , Educação Médica/estatística & dados numéricos , Pesquisas sobre Atenção à Saúde , Patologia/educação , Patologia/estatística & dados numéricos , Publicações Periódicas como Assunto , Currículo , Educação de Graduação em Medicina , Avaliação Educacional , Geografia , Inquéritos e Questionários
20.
Bioresour Technol ; 100(17): 3974-81, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19362828

RESUMO

Thermal properties of compost bulking materials affect temperature and biodegradation during the composting process. Well determined thermal properties of compost feedstocks will therefore contribute to practical thermodynamic approaches. Thermal conductivity, thermal diffusivity, and volumetric heat capacity of 12 compost bulking materials were determined in this study. Thermal properties were determined at varying bulk densities (1, 1.3, 1.7, 2.5, and 5 times uncompacted bulk density), particle sizes (ground and bulk), and water contents (0, 20, 50, 80% of water holding capacity and saturated condition). For the water content at 80% of water holding capacity, saw dust, soil compost blend, beef manure, and turkey litter showed the highest thermal conductivity (K) and volumetric heat capacity (C) (K: 0.12-0.81 W/m degrees C and C: 1.36-4.08 MJ/m(3) degrees C). Silage showed medium values at the same water content (K: 0.09-0.47 W/m degrees C and C: 0.93-3.09 MJ/m(3) degrees C). Wheat straw, oat straw, soybean straw, cornstalks, alfalfa hay, and wood shavings produced the lowest K and C values (K: 0.03-0.30 W/m degrees C and C: 0.26-3.45 MJ/m(3) degrees C). Thermal conductivity and volumetric heat capacity showed a linear relationship with moisture content and bulk density, while thermal diffusivity showed a nonlinear relationship. Since the water, air, and solid materials have their own specific thermal property values, thermal properties of compost bulking materials vary with the rate of those three components by changing water content, bulk density, and particle size. The degree of saturation was used to represent the interaction between volumes of water, air, and solids under the various combinations of moisture content, bulk density, and particle size. The first order regression models developed in this paper represent the relationship between degree of saturation and volumetric heat capacity (r=0.95-0.99) and thermal conductivity (r=0.84-0.99) well. Improved knowledge of the thermal properties of compost bulking materials can contribute to improved thermodynamic modeling and heat management of composting processes.


Assuntos
Eliminação de Resíduos , Solo , Temperatura , Difusão , Análise de Regressão
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