RESUMO
BACKGROUND: In the U.S., lung cancer accounts for 14% of cancer diagnoses and 28% of cancer deaths annually. Since no cure exists for advanced lung cancer, the main treatment goal is to prolong survival. Chemotherapy regimens produce side effects with different profiles. Coupling this with individual patient's preferred side effects could result in patient-centered choices leading to better treatment outcomes. There are apparently no previous studies of or tools for assessing and utilizing patient chemotherapy preferences in clinical settings. The long-term goal of the study was to facilitate patients' treatment choices for advanced-stage lung cancer. A primary aim was to determine how preferences for chemotherapy side effects relate to chemotherapy choices. METHODS: An observational, longitudinal, open cohort study of patients with advanced-stage non-small cell lung cancer (NSCLC) was conducted. Data sources included patient medical records and from one to three interviews per subject. Data were analyzed using Chi-square, Fisher's Exact and McNamara's test, and logistic regression. RESULTS: Patients identified the top three chemotherapy side effects that they would most like to avoid: shortness of breath, bleeding, and fatigue. These side effects were similar between first and last interviews, although the rank order changed after patients experienced chemotherapy. CONCLUSIONS: Patients ranked drug side effects that they would most like to avoid. Patient-centered clinical care and patient-centered outcomes research are feasible and may be enhanced by stakeholder commitment. The study results are limited to patients with advanced NSCLC. Most of the subjects were White, since patients were drawn from the U.S. Midwest, a predominantly White population.
Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Neoplasias Pulmonares/epidemiologia , Preferência do Paciente , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Feminino , Humanos , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Fatores SocioeconômicosRESUMO
AIM: Approximately 20% of patients treated with neoadjuvant chemoradiotherapy (nCRT) for locally advanced rectal cancer achieve a pathological complete response (pCR) while the remainder derive the benefit of improved local control and downstaging and a small proportion show a minimal response. The ability to predict which patients will benefit would allow for improved patient stratification directing therapy to those who are likely to achieve a good response, thereby avoiding ineffective treatment in those unlikely to benefit. METHOD: A systematic review of the English language literature was conducted to identify pathological factors, imaging modalities and molecular factors that predict pCR following chemoradiotherapy. PubMed, MEDLINE and Cochrane Database searches were conducted with the following keywords and MeSH search terms: 'rectal neoplasm', 'response', 'neoadjuvant', 'preoperative chemoradiation', 'tumor response'. After review of title and abstracts, 85 articles addressing the prediction of pCR were selected. RESULTS: Clear methods to predict pCR before chemoradiotherapy have not been defined. Clinical and radiological features of the primary cancer have limited ability to predict response. Molecular profiling holds the greatest potential to predict pCR but adoption of this technology will require greater concordance between cohorts for the biomarkers currently under investigation. CONCLUSION: At present no robust markers of the prediction of pCR have been identified and the topic remains an area for future research. This review critically evaluates existing literature providing an overview of the methods currently available to predict pCR to nCRT for locally advanced rectal cancer. The review also provides a comprehensive comparison of the accuracy of each modality.
Assuntos
Quimiorradioterapia , Terapia Neoadjuvante , Recidiva Local de Neoplasia/etiologia , Neoplasias Retais/patologia , Biomarcadores Tumorais/análise , Humanos , Recidiva Local de Neoplasia/patologia , Neoplasias Retais/terapia , Medição de Risco/métodos , Resultado do TratamentoRESUMO
AIM: Pathological complete response to neoadjuvant chemoradiotherapy is found in 20% of patients with rectal cancer undergoing long-course chemoradiotherapy. Some authors have suggested that these patients do not need to undergo surgery and can be managed with careful follow-up, with surgery only used in the event of clinical failure. Widespread adoption of this regimen is limited by the accuracy of methods to confirm a pathological complete response (pCR). METHOD: A systematic search of PubMed, Medline and Cochrane databases was conducted to identify clinical, histological and radiological features in those patients with rectal cancer who achieved a pCR following chemoradiotherapy. Searches were conducted with the following keywords and MeSH search terms: 'rectal neoplasm', 'response', 'neoadjuvant', 'preoperative chemoradiation' and 'tumour response'. After review of title and abstracts, 89 articles addressing the assessment of pCR were identified. RESULTS: Histology and clinical assessment are the most effective methods of assessment of pCR, with histology considered the gold standard. Clinical assessment is limited to low rectal tumours and is open to significant inter-rater variability, while histological examination requires a surgical specimen. Diffusion-weighted MRI and (18) F-fluorodeoxyglucose positron emission tomography/CT demonstrate the greatest potential for the assessment of pCR, but both modalities have limited accuracy. CONCLUSION: Determination of a pCR is crucial if a nonoperative approach is to be undertaken proactively. Various methods are available, but currently they lack sufficient sensitivity and specificity to define management. This is likely to be an area of further research in the future.
Assuntos
Quimiorradioterapia/métodos , Terapia Neoadjuvante/métodos , Recidiva Local de Neoplasia/patologia , Neoplasias Retais/patologia , Neoplasias Retais/terapia , Biópsia por Agulha , Colectomia/métodos , Terapia Combinada , Feminino , Humanos , Imuno-Histoquímica , Masculino , Invasividade Neoplásica/patologia , Recidiva Local de Neoplasia/epidemiologia , Estadiamento de Neoplasias , Prognóstico , Neoplasias Retais/mortalidade , Medição de Risco , Análise de Sobrevida , Resultado do TratamentoRESUMO
A biomechanical musculo-skeletal model of functional electrical stimulation (FES)-induced rat ankle motion was implemented and tested in rat experiments. The muscle model is a new Hill-based model which includes established physiological relations of force-velocity and force-length-frequency. However, the series-elastic component and the activation component of previous Hill-based models are replaced by a new component which accounts for dynamic time delays and recruitment that occur in real muscle force generation during limb movements. The skeletal model includes gravity and dynamic forces that occur in real rat ankle motions. In computer simulations, various FES patterns were applied to the tibialis anterior (TA) and soleus (SO) model muscles to produce walk-like ankle motions. In lab experiments, the same stimulation patterns were applied by epimysial electrodes implanted in the TA and SO muscles of live rats cordotomized at level T7. The resulting rat motions were recorded by video camera. Video data was converted to ankle angle-vs-time files for comparison with corresponding model angle-vs-time files. Over a physiologically significant range of ankle motions, model parameters were adjustable to yield model motions that agreed with rat motions to within 2 degrees (root mean square differences of rat and model ankle angles). This is shown in plots of model and rat motions presented here for representative cases of FES. The accuracy of our model in reproducing real ankle motions supports the hypothesis that our new muscle model generates correct muscle forces over a useful range of limb motions. It suggests that the model may be useful in the design of FES neural prostheses.
Assuntos
Tornozelo/fisiologia , Modelos Biológicos , Sistema Musculoesquelético , Animais , Articulação do Tornozelo/fisiologia , Ratos , Ratos Sprague-DawleyRESUMO
The ELISPOT assay is a highly sensitive technique used for the detection of individual cytokine releasing cells. We have developed an IFN-gamma ELISPOT assay utilizing unfractionated frozen peripheral blood mononuclear cells (PBMC) to quantify the frequency of measles virus (MV)-specific IFN-gamma-secreting T cells in 117 healthy children who had been previously immunized with two doses of the measles-mumps-rubella vaccine. We have also estimated the variability associated with the quantification of ELISPOT plates and compared the number of MV-specific IFN-gamma-secreting T cells for each subject as determined by two different operators of an ELISPOT reader. The median frequency of MV-specific IFN-gamma-producing memory T cells detected by this assay was 0.005 % and 0.01 % as determined by an in-house and commercial operator, respectively. Although we found a significant correlation (r = 0.83, p<0.0001) between the number of spots counted by the commercial and in-house operators of an ELISPOT reader, the median number of spots counted by the commercial operator was twice the number of spots counted by an in-house operator (p<0.001). This demonstrates the importance of using a common ELISPOT reader and operator, among other parameters, to quantify the number of spots when a large volume of plates are being scanned and analyzed.
Assuntos
Imunoensaio/normas , Interferon gama/análise , Interferon gama/metabolismo , Vírus do Sarampo/imunologia , Linfócitos T/imunologia , Linfócitos T/metabolismo , Adolescente , Criança , Feminino , Humanos , Interferon gama/imunologia , Masculino , Vacina contra Sarampo-Caxumba-Rubéola/imunologia , Reprodutibilidade dos Testes , Especificidade por SubstratoRESUMO
Immunity to measles is conferred by the interplay of humoral and cellular immune responses, the latter being critical in maintaining long-term recall response. Therefore, it is important to evaluate measles-specific humoral and cellular immunity in populations several years after vaccination and understand the correlations among these measures of immunity. We examined measles-specific antibodies, lymphoproliferation and the Th1/Th2 signature cytokines, interferon (IFN)-gamma and interleukin (IL)-4, in a population-based cohort of healthy children from Olmsted County, Minnesota after two doses of measles-mumps-rubella-II (MMR-II) vaccine. We detected positive measures of measles-specific cellular and humoral immunity in the majority of our study population. However, a small proportion of subjects demonstrated an immune response skewed towards the Th2 type, characterized by the presence of either IL-4 and/or measles-specific antibodies and a lack of IFN-gamma production. Further, we observed a significant positive correlation between lymphoproliferation and secretion of IFN-gamma (r = 0.20, P = 0.0002) and IL-4 (r = 0.15, P = 0.005). Measles antibody levels were correlated with lymphoproliferation (r = 0.12, P = 0.03), but lacked correlation to either cytokine type. In conclusion, we demonstrated the presence of both long-term cellular and humoral responses after MMR-II vaccination in a significant proportion of study subjects. Further, a positive correlation between lymphoproliferation and IL-4 and IFN-gamma suggests that immunity to measles may be maintained by both Th1 and Th2 cells. We speculate that the Th2 biased response observed in a subset of our subjects may be insufficient to provide long-term immunity against measles. Further examination of the determinants of Th1 versus Th2 skewing of the immune response and long-term follow-up is needed.
Assuntos
Anticorpos Antivirais/imunologia , Citocinas/imunologia , Vírus do Sarampo/imunologia , Vacina contra Sarampo-Caxumba-Rubéola/imunologia , Linfócitos T Auxiliares-Indutores/imunologia , Adolescente , Fatores Etários , Anticorpos Antivirais/biossíntese , Especificidade de Anticorpos/imunologia , Criança , Feminino , Humanos , Imunidade Celular/imunologia , Imunoglobulina G/análise , Interferon gama/imunologia , Interleucina-4/imunologia , Masculino , Vacina contra Sarampo-Caxumba-Rubéola/administração & dosagem , Células Th1/imunologia , Células Th2/imunologiaRESUMO
We describe a protein with the hallmarks of a chemokine, designated CXCL16, that is made by dendritic cells (DCs) in lymphoid organ T cell zones and by cells in the splenic red pulp. CXCL16 contains a transmembrane domain and both membrane-bound and soluble forms are produced. Naïve CD8 T cells, natural killer T cells and a subset of memory CD4 T cells bind CXCL16, and activated T cells migrated chemotactically to the soluble chemokine. By expression cloning, Bonzo (also known as STRL33 and TYMSTR) was identified as a CXCL16 receptor. CXCL16 may function in promoting interactions between DCs and CD8 T cells and in guiding T cell movements in the splenic red pulp. CXCL16 was also found in the thymic medulla and in some nonlymphoid tissues, indicating roles in thymocyte development and effector T cell trafficking.
Assuntos
Quimiocinas CXC/imunologia , Células Dendríticas/imunologia , Receptores de Citocinas/imunologia , Receptores Acoplados a Proteínas G , Receptores de HIV/imunologia , Receptores Imunológicos , Receptores Virais , Sequência de Aminoácidos , Animais , Quimiocina CXCL16 , Quimiocina CXCL6 , Quimiocinas CXC/genética , Humanos , Ligantes , Proteínas de Membrana/genética , Proteínas de Membrana/imunologia , Camundongos , Dados de Sequência Molecular , Receptores CXCR6 , Receptores de Quimiocinas , Receptores de Citocinas/genética , Receptores de HIV/genética , Receptores Depuradores , Baço/imunologia , Linfócitos T/imunologiaRESUMO
The extremely resorbed edentulous mandible has always presented difficulties for the dentist and patient. This paper describes the use of a heat-cured soft liner to aid in patient comfort. The liner has other applications, notably with cleft palate and oral cancer patients.
Assuntos
Reembasadores de Dentadura , Dimetilpolisiloxanos , Elastômeros de Silicone , Reembasamento de Dentadura , Humanos , Obturadores PalatinosRESUMO
Transfer of the phosphate group of 2-carboxy-D-arabinitol 1-phosphate (CA1P) to 14C-labelled 2-carboxy-D-arabinitol (CA) was catalysed by extracts from leaves of Phaseolus vulgaris. This phosphotransferase activity co-purified with CA1P phosphatase, described previously. This activity was increased, up to 16-fold, by addition of bicarbonate ions at pH 9-10, suggesting rate enhancement by enzyme carbamylation. A V(max) of 1.5 mumol/min per mg of protein and a K(m) (for CA) of 1.8 mM were estimated for the exchange reaction, with the purified phosphatase. 2-Carboxy-D-arabinitol 1,5-bisphosphate and 2-carboxy-D-ribitol 1,5-bisphosphate, but not D-ribulose 1,5-bisphosphate, could replace CA1P as phosphate donor to [14C]CA.
Assuntos
Fabaceae/enzimologia , Pentosefosfatos/metabolismo , Monoéster Fosfórico Hidrolases/metabolismo , Fosfotransferases/metabolismo , Plantas Medicinais , Álcoois Açúcares/metabolismo , Extratos Celulares , Cromatografia em Camada Fina , Concentração de Íons de Hidrogênio , Cinética , Modelos Químicos , Fosfatos/metabolismo , Monoéster Fosfórico Hidrolases/isolamento & purificação , Fosforilação , Fosfotransferases/isolamento & purificação , Bicarbonato de Sódio/farmacologia , Especificidade por SubstratoRESUMO
The use of Molloplast-B silicone rubber for the past 25 years is reviewed. A variety of applications as well as techniques are described. The liner has shown to be acceptable to patients and has aided in their rehabilitation. This processed soft liner is still a viable alternative, even with today's trends in removable prosthodontic service.
Assuntos
Materiais Biocompatíveis , Reembasadores de Dentadura , Dimetilpolisiloxanos , Elastômeros de Silicone , Materiais Biocompatíveis/química , Humanos , Elastômeros de Silicone/químicaRESUMO
The demands for surgical obturators, both in numbers and time restraints, is ever increasing. A quick, simple method to provide these obturators by using the light-cured resins that are currently available is described.
Assuntos
Maxila/cirurgia , Obturadores Palatinos , Desenho de Prótese , Humanos , Fatores de TempoRESUMO
Under matrix management, an organization can recognize and coordinate both its need to implement sweeping changes and its need to maintain day-to-day operations.
Assuntos
Administração Hospitalar , Pessoal Administrativo , Departamentos Hospitalares/organização & administração , Humanos , Modelos Teóricos , Papel (figurativo) , Mudança SocialRESUMO
A procedure was presented to provide an esthetic result in the treatment of electrical burns to the mouth. A removable prosthesis controls the degree of scarring, contracture, and deformity that often occurs from the surgical repair of these burns.
Assuntos
Queimaduras por Corrente Elétrica/terapia , Lábio/lesões , Boca/lesões , Próteses e Implantes , Queimaduras por Corrente Elétrica/cirurgia , Desbridamento , Humanos , Desenho de PróteseRESUMO
A mouth splint has been designed tp be worn through the healing period of an electrical burn of the mouth. The splint is custom-fitted for each child, and it is easily removed. Six children have been so treated and followed up for 4 years. The results to date have been excellent in preventing microstomia.