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1.
Int J Radiat Oncol Biol Phys ; 111(3S): e322-e323, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34701181

RESUMO

PURPOSE/OBJECTIVE(S): Radiation courses generally involve multiple visits over the course of weeks, depending on the disease site and treatment technique. Therefore, radiation therapy (RT) may be discontinued prior to planned treatment completion. The purpose of this analysis is to identify any clinical or socioeconomic factors that could serve as predictors of RT discontinuation. MATERIALS/METHODS: Using the National Cancer Database (NCDB) data from 2017, we identified 7,561 cases treated with RT, chemoradiation (CRT), surgery with RT (S+RT), or surgery with CRT (S+CRT) that had information on radiation discontinuation. The variables that we assessed include age (18- < 50, 50- < 70, 70+), gender (male, female), race (White, Black, other), insurance status (private, Medicare, Medicaid/uninsured, other government), income level (< $30,000, $30,000- < $35,000, $35,000- < $46,000, $46,000+), Charlson-Deyo Comorbidity Score (0, 1, ≥2), treatment type (RT, CRT, S+RT or S+CRT), disease site, and distance from patient residence to treatment facility. RT discontinuation was compared to socioeconomic and clinicopathologic characteristics using chi-square analysis for categorical predictors and Wilcoxon-Mann-Whitney test for continuous predictors. RESULTS: Of the 7,561 patients with information on RT discontinuation, 7,349 (97.2%) patients completed RT, whereas RT was discontinued in 212 (2.8%) patients. The reasons for discontinuation are shown in Table 1. Patients who are 70+ years old (3.7%, P = 0.008), male (3.4%, P = 0.014), Black (3.2%, P = 0.030), Medicaid/uninsured (3.9%, P < 0.0001), income < $30,000 (4.9%, P < 0.0001) and Charlson-Deyo Comorbidity Score ≥2 (3.9%, P = 0.005) had the highest percentages of RT discontinuation in their respective categories. By treatment type, CRT (5.94%) had the highest discontinuation rates, followed by RT (3.1%), S+CRT (2.1%), and S+RT (1.8%), P < 0.0001. Disease site correlated with RT discontinuation (P < 0.0001) with the highest rates of RT discontinuation for cancers of the urinary tract (8.8%), head and neck (6.2%), and respiratory tract (6.0%). The median distance between patient residence and treatment facility was 11.2 and 9.6 miles for patients in the RT completion and RT discontinuation groups, respectively (P = 0.294). CONCLUSION: In this NCDB analysis, both clinical and socioeconomic characteristics, including age, gender, race, insurance status, income level, comorbidities, treatment type, and disease site, correlated with RT discontinuation rates. While toxicity of treatment was reported, patient decision was the most common reason for RT discontinuation. Table 1. Reasons for RT discontinuation (N = 212).

2.
Int J Radiat Oncol Biol Phys ; 111(3S): e444, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34701469

RESUMO

PURPOSE/OBJECTIVE(S): The optimal delivery schedule for stereotactic body radiation therapy (SBRT) in treating Stage I non-small cell lung cancer (NSCLC) is unknown. This study utilized the National Cancer Database (NCDB) to examine daily vs. every other day (QOD) SBRT scheduling in the United States, including trends over time and association with survival. MATERIALS/METHODS: The NCDB was used to identify patients with Stage I NSCLC treated with 3, 4, or 5 fraction SBRT between 2004-2016. Daily scheduling was defined as completing SBRT in 3, 4, or 5 days, respectively. QOD scheduling for 3, 4, and 5 fractions was defined as SBRT completion in 5-9, 8-12, and 10-14 days, respectively. Survival analysis was performed using the Kaplan-Meier method and Cox regression modeling. The multivariate model included age, gender, race, insurance status, median income, Charlson-Deyo comorbidity score, clinical T stage, histology, and facility type. RESULTS: Of 15,269 patients who met study criteria, 3,927 (25.7%) received SBRT daily, and 11,342 (74.3%) received treatment QOD. A total of 4,993 (32.7%), 4,278 (28.0%), and 5,998 (39.3%) patients received 3, 4, and 5 fractions, respectively. The most common dose fractionations were 10 Gy x 5 (26.7%), 12 Gy x 4 (18.4%), and 18 Gy x 3 (17.3%). Factors significantly associated with daily SBRT scheduling included lower income (P < 0.0001), lower comorbidities (P = 0.0019), and treatment at academic/research programs (P < 0.0001). The use of daily SBRT scheduling decreased from a peak of 36.8% in 2007 to 21.7% in 2016, while QOD treatment increased from a nadir of 63.2% in 2007 to 78.3% in 2016 (both P < 0.0001). The use of 3-fraction SBRT decreased over time from 81.5% in 2004 to 23.4% in 2016, while 5-fraction SBRT increased from 3.7% in 2004 to 51.4% in 2016 (both P < 0.0001); there was no significant change in use of 4-fraction regimens (P = 0.6). The most common treatment schedule was 3 fractions QOD from 2004-2011 (25.5-70.4%), while more recently 5 fractions QOD was most prevalent from 2012-2016 (rising from 28.5% in 2012 to 41.6% in 2016). Median follow-up was 28.9 months, and median survival was 38.3 months. Median survival for patients who received daily SBRT was 37.9 months vs. 38.4 months for QOD (P = 0.4). On multivariate analysis, no difference was found in overall survival between daily vs. QOD scheduling (hazard ratio [HR] 0.99 [95% confidence interval 0.94-1.04]; P = 0.6). With 3-fraction SBRT, QOD treatment was associated with improved survival vs. daily treatment (HR 0.91 [0.84-0.98]; P = 0.02). With 5-fraction SBRT, QOD treatment was associated with worse survival vs. daily treatment (HR 1.11 [1.02-1.22]; P = 0.02). CONCLUSION: In this NCDB analysis, QOD SBRT schedules were more frequently used to treat Stage I NSCLC than daily regimens by a factor of 3:1. QOD scheduling increased over time, as did 5-fraction treatments, with 5-fraction QOD becoming the most common dose schedule after 2012. No clear association was found between daily vs. QOD scheduling and overall survival.

3.
Braz. j. biol ; 80(3): 565-573, July-Sept. 2020. tab
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1132399

RESUMO

Abstract Due to increased number of herbicide resistant weeds, it is needed to explore the allelopathic potential of plants as an alternative. The research was conducted to investigate allelopathic effects of Carica papaya L. leaf powder and aqueous extract on seeds as well as pre-germinated seeds of Avena fatua L., Helianthus annuus L., Rumex dentatus L., Zea mays L. and Triticum aestivum L. on filter paper and soil in Weed Management Program Laboratory, Department of Plant and Environmental Protection at PARC Institute of Advanced Studies in Agriculture, National Agriculture Research Centre, Islamabad, Pakistan. Germination percentage (%), radicle length (cm) and plumule length (cm) were parameters observed for 'Plant leaf powder bioassay' and 'Aqueous extract method'. Most significant growth inhibition was observed in A. fatua seedlings in filter paper method. A. fatua radicle length was reduced by C. papaya aqueous extract (80%) and leaf powder (89%) bioassays. Plumule length was reduced under the influence of aqueous extract (57-73%) and powdered material (59-77%). The inhibitory effects on other test species were in sequence of H. annuus followed by Z. mays and R. dentatus. The aqueous extract showed non-significant effect on wheat seed germination, radicle and plumule growth. It is suggested that C. papaya aqueous extract can be used as source of weed management in wheat crop.


Resumo Devido ao aumento do número de ervas daninhas resistentes aos herbicidas, é necessário explorar o potencial alelopático das plantas como uma alternativa. A pesquisa foi conduzida com o objetivo de investigar os efeitos alelopáticos do pó foliar de Carica papaya e do extrato aquoso das sementes, bem como das sementes pré-germinadas de Avena fatua, Helianthus annuus, Rumex dentatus, Zea mays e Triticum aestivum em papel de filtro e solo no Laboratório do Programa de Manejo de Ervas Daninhas, Departamento de Plantas e Proteção Ambiental do Instituto PARC de Estudos Avançados em Agricultura, Centro Nacional de Pesquisa Agrícola, Islamabad, Paquistão. A porcentagem de germinação (%), o comprimento radicular e o comprimento da plúmula (cm) foram os parâmetros observados para o 'Bioensaio de Pó de Folha de Planta' e o 'Método de Extração Aquoso'. A maior inibição do crescimento foi observada em mudas de A. fatua no método de papel de filtro. O comprimento radicular de A. fatua foi reduzido com os extratos aquosos de C. papaya (80%) e pó de folhas (89%). O comprimento das plúmulas foi reduzido sob a influência do extrato aquoso (57-73%) e material em pó (59-77%). Os efeitos inibitórios em outras espécies-teste foram na sequência de H. annuus seguido por Z. mays e R. dentatus. O extrato aquoso apresentou efeito não significativo na germinação das sementes de trigo, nos crescimentos radiculares e das plúmulas. Sugere-se que o extrato aquoso de C. papaya pode ser utilizado como fonte de manejo de plantas daninhas na cultura do trigo.

4.
Braz J Biol ; 80(3): 565-573, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31644650

RESUMO

Due to increased number of herbicide resistant weeds, it is needed to explore the allelopathic potential of plants as an alternative. The research was conducted to investigate allelopathic effects of Carica papaya L. leaf powder and aqueous extract on seeds as well as pre-germinated seeds of Avena fatua L., Helianthus annuus L., Rumex dentatus L., Zea mays L. and Triticum aestivum L. on filter paper and soil in Weed Management Program Laboratory, Department of Plant and Environmental Protection at PARC Institute of Advanced Studies in Agriculture, National Agriculture Research Centre, Islamabad, Pakistan. Germination percentage (%), radicle length (cm) and plumule length (cm) were parameters observed for 'Plant leaf powder bioassay' and 'Aqueous extract method'. Most significant growth inhibition was observed in A. fatua seedlings in filter paper method. A. fatua radicle length was reduced by C. papaya aqueous extract (80%) and leaf powder (89%) bioassays. Plumule length was reduced under the influence of aqueous extract (57-73%) and powdered material (59-77%). The inhibitory effects on other test species were in sequence of H. annuus followed by Z. mays and R. dentatus. The aqueous extract showed non-significant effect on wheat seed germination, radicle and plumule growth. It is suggested that C. papaya aqueous extract can be used as source of weed management in wheat crop.


Assuntos
Carica , Germinação , Paquistão , Extratos Vegetais , Folhas de Planta , Sementes
5.
AJNR Am J Neuroradiol ; 40(3): 551-557, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30792250

RESUMO

BACKGROUND AND PURPOSE: Our aim was to identify whether specific patterns of ossification in labyrinthitis ossificans are associated with the known risk factors. Labyrinthitis ossificans has been described as sequela of prior temporal bone trauma, prior infection, and other disorders including sickle cell disease. Specific patterns of mineralization in the membranous labyrinth associated with these risk factors has not been previously described. MATERIALS AND METHODS: This was a retrospective study evaluating temporal bone CT scans at our institution from November 2005 to May 2018 in patients with labyrinthitis ossificans. Membranous labyrinthine structures evaluated for ossification included the following: basal, middle, and apical cochlear turns; lateral, posterior, and superior semicircular canals; and the vestibule for both ears in all patients. These structures were assigned a severity score, 0-4, based on degree of mineralization. Clinical records were reviewed for potential labyrinthitis ossificans risk factors. Basic descriptive statistics and a mixed model were used to correlate the degree and patterns of ossification with clinical history. RESULTS: Forty-four patients (58 ears) with labyrinthitis ossificans were identified and evaluated. The most common risk factors were chronic otomastoiditis (n = 18), temporal bone surgery (n = 9), temporal bone trauma (n = 6), sickle cell disease (n = 5), and meningitis (n = 4). For all etiologies, the semicircular canals were most severely affected, and the vestibule was the least. In patients with prior temporal bone surgery, significantly greater mineralization was seen in the basal turn of the cochlea (P = .027), the vestibule (P = .001), and semicircular canals (P < .001-.008). No significant pattern was identified in patients with meningitis, sickle cell disease, or trauma. CONCLUSIONS: Significant patterns of mineralization in labyrinthitis ossificans were observed in patients with prior temporal bone surgery. For all etiologies, the semicircular canals were most severely affected. No significant mineralization pattern was observed in patients with chronic otomastoiditis, meningitis, sickle cell disease, or prior temporal bone trauma.


Assuntos
Labirintite/patologia , Ossificação Heterotópica/etiologia , Ossificação Heterotópica/patologia , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Humanos , Labirintite/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Ossificação Heterotópica/diagnóstico por imagem , Estudos Retrospectivos , Fatores de Risco , Tomografia Computadorizada por Raios X , Adulto Jovem
6.
AJNR Am J Neuroradiol ; 40(3): 543-550, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30792253

RESUMO

BACKGROUND AND PURPOSE: Differentiating nodal metastases from reactive adenopathy in HIV-infected patients with [18F] FDG-PET/CT can be challenging because lymph nodes in HIV-positive patients often show increased [18F] FDG uptake. The purpose of this study was to assess CT textural analysis characteristics of HIV-positive and HIV-negative lymph nodes on [18F] FDG-PET/CT to differentiate nodal metastases from disease-specific nodal reactivity. MATERIALS AND METHODS: Nine HIV-positive patients with head and neck squamous cell carcinoma (7 men, 2 women; 29-62 years of age; median age, 48 years) with 22 lymph nodes (≥1 cm) who underwent contrast-enhanced CT with [18F] FDG-PET followed by pathologic evaluation of cervical lymph nodes were retrospectively reviewed. Twenty-six HIV-negative patients with head and neck squamous cell carcinoma with 61 lymph nodes were evaluated as a control group. Each lymph node was manually segmented, and an in-house-developed Matlab-based texture analysis program extracted 41 texture features from each segmented volume. A mixed linear regression model was used to compare the pathologically proved malignant lymph nodes with benign nodes in the 2 enrolled groups. RESULTS: Thirteen (59%) lymph nodes in the HIV-positive group and 22 (36%) lymph nodes in the HIV-negative control group were confirmed as positive for metastases. There were 7 histogram features (P = .017-0.032), 3 gray-level co-occurrence features (P = .009-.025), and 9 gray-level run-length features (P < .001-.033) that demonstrated a significant difference in HIV-positive patients with either benign or malignant lymph nodes. CONCLUSIONS: CT texture analysis may be useful as a noninvasive method of obtaining additional quantitative information to differentiate nodal metastases from disease-specific nodal reactivity in HIV-positive patients with head and neck squamous cell carcinoma.


Assuntos
Interpretação de Imagem Assistida por Computador/métodos , Linfadenopatia/diagnóstico por imagem , Metástase Linfática/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Carcinoma de Células Escamosas de Cabeça e Pescoço/diagnóstico por imagem , Adulto , Diagnóstico Diferencial , Feminino , Fluordesoxiglucose F18 , Infecções por HIV/complicações , Infecções por HIV/patologia , Humanos , Linfadenopatia/etiologia , Linfadenopatia/virologia , Metástase Linfática/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Sensibilidade e Especificidade , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/virologia
7.
AJNR Am J Neuroradiol ; 38(12): 2334-2340, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29025727

RESUMO

BACKGROUND AND PURPOSE: The accurate prediction of prognosis and failure is crucial for optimizing treatment strategies for patients with cancer. The purpose of this study was to assess the performance of pretreatment CT texture analysis for the prediction of treatment failure in primary head and neck squamous cell carcinoma treated with chemoradiotherapy. MATERIALS AND METHODS: This retrospective study included 62 patients diagnosed with primary head and neck squamous cell carcinoma who underwent contrast-enhanced CT examinations for staging, followed by chemoradiotherapy. CT texture features of the whole primary tumor were measured using an in-house developed Matlab-based texture analysis program. Histogram, gray-level co-occurrence matrix, gray-level run-length, gray-level gradient matrix, and Laws features were used for texture feature extraction. Receiver operating characteristic analysis was used to identify the optimal threshold of any significant texture parameter. We used multivariate Cox proportional hazards models to examine the association between the CT texture parameter and local failure, adjusting for age, sex, smoking, primary tumor stage, primary tumor volume, and human papillomavirus status. RESULTS: Twenty-two patients (35.5%) developed local failure, and the remaining 40 (64.5%) showed local control. Multivariate analysis revealed that 3 histogram features (geometric mean [hazard ratio = 4.68, P = .026], harmonic mean [hazard ratio = 8.61, P = .004], and fourth moment [hazard ratio = 4.56, P = .048]) and 4 gray-level run-length features (short-run emphasis [hazard ratio = 3.75, P = .044], gray-level nonuniformity [hazard ratio = 5.72, P = .004], run-length nonuniformity [hazard ratio = 4.15, P = .043], and short-run low gray-level emphasis [hazard ratio = 5.94, P = .035]) were significant predictors of outcome after adjusting for clinical variables. CONCLUSIONS: Independent primary tumor CT texture analysis parameters are associated with local failure in patients with head and neck squamous cell carcinoma treated with chemoradiotherapy.


Assuntos
Carcinoma de Células Escamosas/diagnóstico por imagem , Carcinoma de Células Escamosas/patologia , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Neoplasias de Cabeça e Pescoço/patologia , Interpretação de Imagem Assistida por Computador/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/terapia , Quimiorradioterapia , Feminino , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Curva ROC , Estudos Retrospectivos , Fatores de Risco , Carcinoma de Células Escamosas de Cabeça e Pescoço , Tomografia Computadorizada por Raios X/métodos
8.
AJNR Am J Neuroradiol ; 38(5): 981-985, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28341714

RESUMO

Our aim was to evaluate changes in texture features based on variations in CT parameters on a phantom. Scans were performed with varying milliampere, kilovolt, section thickness, pitch, and acquisition mode. Forty-two texture features were extracted by using an in-house-developed Matlab program. Two-tailed t tests and false-detection analyses were performed with significant differences in texture features based on detector array configurations (Q values = 0.001-0.006), section thickness (Q values = 0.0002-0.001), and acquisition mode (Q values = 0.003-0.006). Variations in milliampere and kilovolt had no significant effect.


Assuntos
Processamento de Imagem Assistida por Computador/métodos , Tomografia Computadorizada por Raios X/métodos , Humanos , Imagens de Fantasmas , Projetos Piloto
9.
AJNR Am J Neuroradiol ; 36(7): 1343-8, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25836725

RESUMO

BACKGROUND AND PURPOSE: Human papillomavirus-associated oropharyngeal squamous cell carcinoma is increasing in prevalence and typically occurs in younger patients than human papillomavirus-negative squamous cell carcinoma. While imaging features of human papillomavirus-positive versus human papillomavirus-negative squamous cell carcinoma nodal metastases have been described, characteristics distinguishing human papillomavirus-positive from human papillomavirus-negative primary squamous cell carcinomas have not been well established. The purpose of this project was to evaluate the use of texture features to distinguish human papillomavirus-positive and human papillomavirus-negative primary oropharyngeal squamous cell carcinoma. MATERIALS AND METHODS: Following institutional review board approval, 40 patients with primary oropharyngeal squamous cell carcinoma and known human papillomavirus status who underwent contrast-enhanced CT between December 2009 and October 2013 were included in this study. Segmentation of the primary lesion was manually performed with a semiautomated graphical-user interface. Following segmentation, an in-house-developed texture analysis program extracted 42 texture features from each segmented volume. A t test was used to evaluate differences in texture parameters between human papillomavirus-positive and human papillomavirus-negative squamous cell carcinomas. RESULTS: Of the 40 included patients, 29 had human papillomavirus-positive oropharyngeal squamous cell carcinoma and 11 had human papillomavirus-negative oropharyngeal squamous cell carcinoma. Significant differences were seen in the histogram parameters median (P = .006) and entropy (P = .016) and squamous cell carcinoma entropy (P = .043). CONCLUSIONS: There are statistically significant differences in some texture features between human papillomavirus-positive and human papillomavirus-negative oropharyngeal tumors. Texture analysis may be considered an adjunct to the evaluation of human papillomavirus status and characterization of squamous cell carcinoma.


Assuntos
Carcinoma de Células Escamosas/virologia , Interpretação de Imagem Assistida por Computador/métodos , Neoplasias Orofaríngeas/virologia , Infecções por Papillomavirus/diagnóstico , Tomografia Computadorizada por Raios X/métodos , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/diagnóstico por imagem , Carcinoma de Células Escamosas/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Orofaríngeas/diagnóstico por imagem , Neoplasias Orofaríngeas/patologia , Infecções por Papillomavirus/epidemiologia
10.
AJNR Am J Neuroradiol ; 32(7): 1195-201, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21757530

RESUMO

BACKGROUND AND PURPOSE: Tumor hypoxia is a known factor of radioresistance in HNSCC. CTP is a noninvasive method of measuring tumor perfusion in vivo. The purpose of our study was to determine serial changes in tumor perfusion in HNSCC during a course of RT by using CTP and to correlate tumor perfusion measurements to LRC. MATERIALS AND METHODS: A prospective study was performed in 15 patients with HNSCC receiving definitive RT who underwent serial CTP before RT; at weeks 2, 4, and 6 of RT; and 6 weeks after RT. The median follow-up was 28 months (range, 6-44 months). Thirteen patients achieved LRC, and 2 patients had LRF. Tumor perfusion parameters, including BF, BV, MTT, and CP, were obtained by using a deconvolution-based analysis. RESULTS: Pretreatment tumor BF was significantly higher in patients who achieved LRC, 118.0 mL/100 g/min, compared with those with LRF, 53.4 mL/100 g/min (P = .004). Similarly, pretreatment CP was higher in patients with LRC, 16.6 mL/100 g/min, compared with those with LRF, 7.7 mL/100 g/min (P = .02). At week 2 of RT, tumor BF parameters showed a 27.5% increase versus an 18.1% decrease from pretreatment BF values (P = .046) in patients with LRC and LRF, respectively. A decrease in BF and BV was observed in both groups 6 weeks after RT compared with these values at baseline scanning. CONCLUSIONS: An increase in tumor BF and CP by using CTP early during a course of RT predicts LRC in patients with HNSCC treated with RT.


Assuntos
Carcinoma de Células Escamosas/diagnóstico por imagem , Carcinoma de Células Escamosas/radioterapia , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Neoplasias de Cabeça e Pescoço/radioterapia , Imagem de Perfusão/métodos , Tomografia Computadorizada por Raios X/métodos , Idoso , Carcinoma de Células Escamosas/irrigação sanguínea , Feminino , Seguimentos , Neoplasias de Cabeça e Pescoço/irrigação sanguínea , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Radioterapia/métodos , Taxa de Sobrevida , Resultado do Tratamento
11.
Neurology ; 75(20): 1766-72, 2010 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-20962290

RESUMO

BACKGROUND: To date, there is no accepted clinical diagnostic test for Parkinson disease (PD) that is based on biochemical analysis of blood or CSF. The discovery of mutations in the SNCA gene encoding α-synuclein in familial parkinsonism and the accumulation of α-synuclein in the PD brain suggested a critical role for this protein in PD etiology. METHODS: We investigated total and α-synuclein oligomers levels in CSF from patients clinically diagnosed with PD, progressive supranuclear palsy (PSP), or Alzheimer disease (AD), and age-matched controls, using ELISA developed in our laboratory. RESULTS: The levels of α-synuclein oligomers and oligomers/total-α-synuclein ratio in CSF were higher in the PD group (n = 32; p < 0.0001, Mann-Whitney U test) compared to the control group (n = 28). The area under the receiver operating characteristic curve (AUC) indicated a sensitivity of 75.0% and a specificity of 87.5%, with an AUC of 0.859 for increased CSF α-synuclein oligomers in clinically diagnosed PD cases. However, when the CSF oligomers/total-α-synuclein ratio was analyzed, it provided an even greater sensitivity of 89.3% and specificity of 90.6%, with an AUC of 0.948. In another cross-sectional pilot study, we confirmed that the levels of CSF α-synuclein oligomers were higher in patients with PD (n = 25) compared to patients with PSP (n = 18; p < 0.05) or AD (n = 35; p < 0.001) or control subjects (n = 43; p < 0.05). CONCLUSION: Our results demonstrate that levels of α-synuclein oligomers in CSF and the oligomers/total-α-synuclein ratio can be useful biomarkers for diagnosis and early detection of PD.


Assuntos
Doença de Parkinson/líquido cefalorraquidiano , Doença de Parkinson/diagnóstico , alfa-Sinucleína/líquido cefalorraquidiano , Adulto , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/líquido cefalorraquidiano , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/metabolismo , Biomarcadores/líquido cefalorraquidiano , Biomarcadores/química , Química Encefálica , Estudos de Coortes , Estudos Transversais/métodos , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/metabolismo , Projetos Piloto , Paralisia Supranuclear Progressiva/líquido cefalorraquidiano , Paralisia Supranuclear Progressiva/diagnóstico , Paralisia Supranuclear Progressiva/metabolismo , Regulação para Cima/fisiologia , alfa-Sinucleína/química
12.
East Afr Med J ; 81(5): 271-3, 2004 May.
Artigo em Inglês | MEDLINE | ID: mdl-15508344

RESUMO

A six year old girl was admitted to the Kenyatta National Hospital paediatric unit with history of headaches, fever, neck stiffness and paraesthesias of the lower limbs. She was empirically commenced on antimeningitic treatment. Her neurological state deteriorated over a period of two months to paraparesis and paraplegia of the lower limbs with urinary and stool incontinence. A neurology review revealed a sensory level at T10 with power grade 2 in the lower limbs. A myelogram revealed a block of contrast at T12. An impression of cord compression by an intraspinal tumour was made. Laminectomy and posterior midline myelotomy was performed. At operation a greyish-white intramedullary mass lesion was found. Histology revealed a schistosoma mansoni ovum surrounded by granulomatous tissue with giant cells and polymorphoneuclear leucocytes. The child was commenced on paziquantel 1000 mg and dexamethasone 24 mg per day in divided doses. There was marked neurological improvement and the patient went home one month later. She was able to walk without support and was continent of urine and stool at the time of discharge.


Assuntos
Esquistossomose mansoni/diagnóstico , Esquistossomose mansoni/terapia , Compressão da Medula Espinal/diagnóstico , Compressão da Medula Espinal/terapia , Anti-Helmínticos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Criança , Dexametasona/uso terapêutico , Feminino , Humanos , Laminectomia , Vértebras Lombares/cirurgia , Praziquantel/uso terapêutico , Esquistossomose mansoni/complicações , Compressão da Medula Espinal/etiologia , Vértebras Torácicas/cirurgia , Resultado do Tratamento
13.
Int J Oncol ; 16(5): 1043-8, 2000 May.
Artigo em Inglês | MEDLINE | ID: mdl-10762643

RESUMO

This report provides evidence linking activation of Ras GTPase by growth factors and induction of glutathione-S-transferase isozymes in PC12 cells. Ras GTPase was activated by EGF, NGF, insulin and phorbolester in PC12 cells. Activation of Ras GTPase was found to be associated with induction of the expression of GST mu and pi isoenzymes while there was no detectable induction of GST alpha expression. GST pi was found to be induced by all the Ras GTPase activating agents tested while activation of Ras by phorbolester and insulin induced expression of GST mu only. These results suggest a role of Ras, at least in part, in controlling the expression of GST and that there might be independent signalling pathways for the expression of different GST isoenzymes. GST activity was found to be very high (4-fold) in the lysate obtained from retinoic acid treated PC12 cells when compared with untreated cells. Induction of GST expression was found to be initiated within 30 min of retinoic acid treatment in PC12 cells reaching a maximum level at 4 h. However, immunoblot analysis showed that retinoic acid (RA), unlike mitogens/growth factors, weakly induced the expression of GST pi but not the expression of alpha, mu and microsomal GSTs. Overxpression of inhibitory polypeptides that block signals generated from Ras and Cdc42 was found to reverse the retinoic acid activation-dependent induction of GST expression in PC12 cells. These results provide evidence for the first time suggesting a novel role of Ras GTPase in the regulation of GST expression which might have a significant implication in developing drug resistance and/or growth of cancer cells.


Assuntos
Genes ras/fisiologia , Glutationa Transferase/metabolismo , Substâncias de Crescimento/farmacologia , Isoenzimas/metabolismo , Animais , Fator de Crescimento Epidérmico/farmacologia , GTP Fosfo-Hidrolases/metabolismo , Regulação Enzimológica da Expressão Gênica , Insulina/farmacologia , Microssomos/enzimologia , Fator de Crescimento Neural/farmacologia , Células PC12 , Ratos , Acetato de Tetradecanoilforbol/farmacologia , Tretinoína/farmacologia
14.
Chirality ; 11(4): 316-8, 1999.
Artigo em Inglês | MEDLINE | ID: mdl-10224659

RESUMO

An asymmetric synthesis of the optically pure isomers of the minor tobacco alkaloid and CNS nicotine metabolite, nornicotine, has been achieved with moderately high optical purity. The synthetic pathway involves alkylation of a chiral ketimine, prepared from either 1R,2R,5R-(+)- or 1S,2S,5S-(-)-2-hydroxy-3-pinanone and 3-(aminomethyl)pyridine with 3-bromopropan-1-ol. After cleavage of the respective C-alkylated ketimines with NH2OH.HCl, and treatment of the resulting amino alcohols with HBr, followed by base-catalyzed intramolecular ring closure, (S)-(-)-nornicotine and (R)-(+)-nornicotine were obtained with ee values of 91% and 81%, respectively.


Assuntos
Nicotina/análogos & derivados , Piridinas , Alquilação , Indicadores e Reagentes , Modelos Moleculares , Conformação Molecular , Estrutura Molecular , Nicotina/síntese química , Nicotina/química , Estereoisomerismo
15.
Hemoglobin ; 23(1): 33-45, 1999 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-10081984

RESUMO

The unstable Hb Khartoum with a Pro-->Arg replacement at position beta124 was identified by isoelectrofocusing, high performance liquid chromatography, and peptide mapping in a mother and two male children of a Sudanese family. All three were heterozygous for the abnormal hemoglobin; the father and a third male child did not carry the mutation. The mother was also homozygous for two putative gamma+-thalassemia point mutations, one affecting both Agamma and Ggamma genes at IVS-II-115 (A-->G), and one affecting the Ggamma gene at the 3' untranslated region (-A) at position -6 from the polyadenylation site. The father had normal gamma genes. All three children were heterozygous for both the gamma+-thalassemia mutations. The two older children, who were compound heterozygotes for Hb Khartoum/gamma+-thalassemia, presented at birth with severe neonatal jaundice which necessitated exchange blood transfusions. Other causes of neonatal jaundice were excluded. The third male child, who did not carry the Hb Khartoum anomaly but was heterozygous for gamma+-thalassemia, did not develop neonatal jaundice. It is concluded that the instability of Hb Khartoum in combination with gamma+-thalassemia is responsible for neonatal hemolytic anemia in this family.


Assuntos
Eritroblastose Fetal/genética , Hemoglobinas Anormais/genética , Adulto , Arginina , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Mutação Puntual , Prolina , Sudão , Talassemia/genética
16.
Oncogene ; 18(54): 7787-93, 1999 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-10618719

RESUMO

Based on the previous experiments with the N17 mutant of CDC42, it has been speculated, but not proved as yet, that CDC42 is required for Ras-induced malignant transformation of fibroblasts. However, since this inhibitor could sequester many GDP-dissociation stimulators (GDSs), such as DBL, OST and Tiam-1 which activate not only CDC42, but also Rho or Rac, in fact it is not a specific inhibitor that inactivates only CDC42. Thus, we have taken the minimum CDC42-binding domain (residues 504 - 545, called ACK42) of the Tyr-kinase ACK-1 that binds only CDC42 in the GTP-bound form, and thereby blocking the interactions of CDC42-GTP with its downstream effectors such as ACKs, PAKs and N-WASP. First of all, using the ACK42-GST fusion protein as a specific ligand for the GTP-CDC42 complex, we have revealed that CDC42 is activated by oncogenic Ras mutants such as v-Ha-Ras in NIH3T3 fibroblasts, and similarly in PC12 cells by both NGF (Nerve Growth Factor) and EGF (Epidermal Growth Factor) which activate the endogenous normal Ras, providing the first direct evidence that CDC42 acts downstream of Ras and NGF/EGF. Furthermore, over-expression of ACK42 completely reversed Ras-induced malignant phenotypes such as focus formation and anchorage/serum-independent growth of the fibroblasts, and a cell-permeable derivative of ACK42 called WR-ACK42 strongly inhibited the growth of Ras transformants, with little effect on the parental normal cell growth, and also abolished Ras-induced filopodium/microspike formation of the fibroblasts which is CDC42-dependent. These observations unambiguously proved for the first time that the RAS-induced activation of CDC42 is indeed essential for Ras to transform the fibroblasts, and furthermore suggest that ACK42 or its peptidomimetics are potentially useful for genotherapy or chemotherapy of Ras-associated cancer.


Assuntos
Transformação Celular Neoplásica , Genes ras , Proteínas Tirosina Quinases/metabolismo , Proteína cdc42 de Ligação ao GTP/metabolismo , Células 3T3 , Animais , Sequência de Bases , Guanosina Trifosfato/metabolismo , Camundongos , Dados de Sequência Molecular , Células PC12 , Proteínas Tirosina Quinases/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Ratos , Proteínas Recombinantes de Fusão/metabolismo , Moldes Genéticos , Trombina/metabolismo , Transfecção , Proteína cdc42 de Ligação ao GTP/antagonistas & inibidores , Proteína cdc42 de Ligação ao GTP/química
18.
East Afr Med J ; 75(11): 671-2, 1998 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-10065185

RESUMO

Magnetic resonance imaging (MRI) is the most suitable modality for evaluation of infectious spondylitis. It is more sensitive than other imaging modalities for detecting presence and extent of such infections. Though it is not always possible to differentiate various infections on the basis of imaging findings alone, there are certain features which along with a good clinical background, can differentiate brucellar spondylitis from other spinal infections. It is useful to follow up such patients after specific chemotherapy to further confirm the diagnosis.


Assuntos
Brucelose/complicações , Vértebras Cervicais , Imageamento por Ressonância Magnética , Espondilite/diagnóstico , Espondilite/microbiologia , Adulto , Animais , Brucelose/tratamento farmacológico , Brucelose/transmissão , Camelus/microbiologia , Cabras/microbiologia , Humanos , Masculino , Leite/microbiologia
19.
Ann Trop Paediatr ; 18(2): 93-9, 1998 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-9924569

RESUMO

All infants born at Al Ain Hospital, United Arab Emirates between 1 January and 30 June 1995 who developed clinically relevant hyperbilirubinaemia defined as jaundice requiring investigation and treatment were prospectively studied. Of the 2300 live births, 85 (3.7%) developed hyperbilirubinaemia. Of these, 22 were premature, 22 had ABO haemolytic disease of the newborn, eight had G6PD deficiency (Mediterranean), seven had breast-milk jaundice, five were born to mothers with diabetes mellitus and one had Rh incompatibility. No specific factor was identified in 20 (24%). Significant differences in the distribution of diagnostic categories were found among the major ethnic groups in the population studied. This first study of the epidemiology of clinically relevant hyperbilirubinaemia in this community identified locally relevant risk factors and highlighted areas of health care which, if modified, might reduce the incidence of hyperbilirubinaemia.


Assuntos
Deficiência de Glucosefosfato Desidrogenase/genética , Icterícia Neonatal/epidemiologia , Ásia Ocidental/etnologia , Aleitamento Materno/efeitos adversos , Eritroblastose Fetal/epidemiologia , Feminino , Deficiência de Glucosefosfato Desidrogenase/epidemiologia , Humanos , Recém-Nascido , Recém-Nascido Prematuro/sangue , Icterícia Neonatal/etiologia , Masculino , Emirados Árabes Unidos/epidemiologia
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