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1.
Artigo em Inglês | MEDLINE | ID: mdl-28929537

RESUMO

Registry data on invasive cervical cancers (n = 1,274) from four major hospitals (1984-2012) were analysed to determine their value for informing local service delivery in Australia. The methodology comprised disease-specific survival analyses using Kaplan-Meier product-limit estimates and Cox proportional hazards models and treatment analyses using logistic regression. Five- and 10-year survivals were 72% and 68%, respectively, equating with relative survival estimates for Australia and the USA. Most common treatments were surgery and radiotherapy. Systemic therapies increased in recent years, generally with radiotherapy, but were less common for residents from less accessible areas. Surgery was more common for younger women and early-stage disease, and radiotherapy for older women and regional and more advanced disease. The proportion of glandular cancers increased in-step with national trends. Little evidence of variation in risk-adjusted survival presented over time or by Local Health District. The study illustrates the value of local registry data for describing local treatment and outcomes. They show the lower use of systemic therapies among residents of less accessible areas which warrants further investigation. Risk-adjusted treatment and outcomes did not vary by socio-economic status, suggesting equity in service delivery. These data are important for local evaluation and were not available from other sources.


Assuntos
Adenocarcinoma/terapia , Carcinoma de Células Escamosas/terapia , Acessibilidade aos Serviços de Saúde , Histerectomia , Radioterapia , Sistema de Registros , Neoplasias do Colo do Útero/terapia , Adenocarcinoma/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Austrália , Carcinoma de Células Escamosas/mortalidade , Bases de Dados Factuais , Atenção à Saúde , Gerenciamento Clínico , Feminino , Humanos , Estimativa de Kaplan-Meier , Modelos Logísticos , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Modelos de Riscos Proporcionais , Análise de Sobrevida , Taxa de Sobrevida , Neoplasias do Colo do Útero/mortalidade
2.
Artigo em Inglês | MEDLINE | ID: mdl-28271574

RESUMO

Monitoring screening mammography effects in small areas is often limited by small numbers of deaths and delayed effects. We developed a risk score for breast cancer death to circumvent these limitations. Screening, if effective, would increase post-diagnostic survivals through lead-time and related effects, as well as mortality reductions. Linked cancer and BreastScreen data at four hospitals (n = 2,039) were used to investigate whether screened cases had higher recorded survivals in 13 small areas, using breast cancer deaths as the outcome (M1), and a risk of death score derived from TNM stage, grade, histology type, hormone receptor status, and related variables (M2). M1 indicated lower risk of death in screened cases in 12 of the 13 areas, achieving statistical significance (p < .05) in 5. M2 indicated lower risk scores in screened cases in all 13 areas, achieving statistical significance in 12. For cases recently screened at diagnosis (<6 months), statistically significant reductions applied in 8 areas (M1) and all 13 areas (M2). Screening effects are more detectable in small areas using these risk scores than death itself as the outcome variable. An added advantage is the application of risk scores for providing a marker of screening effect soon after diagnosis.


Assuntos
Neoplasias da Mama/prevenção & controle , Detecção Precoce de Câncer/estatística & dados numéricos , Distribuição por Idade , Idoso , Neoplasias da Mama/mortalidade , Feminino , Humanos , Mamografia/estatística & dados numéricos , Programas de Rastreamento/estatística & dados numéricos , Pessoa de Meia-Idade , Sistema de Registros , Medição de Risco , Análise de Pequenas Áreas , Fatores Socioeconômicos , Austrália do Sul/epidemiologia
3.
Diabet Med ; 33(9): 1211-21, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-26670627

RESUMO

AIM: High iron measured using dietary intake and biomarkers is associated with Type 2 diabetes. It is uncertain whether a similar association exists for gestational diabetes mellitus. The aim of this systematic review was to conduct a cohort study examining first trimester body iron stores and subsequent risk of gestational diabetes, and to include these findings in a systematic review of all studies examining the association between maternal iron status, iron intake (dietary and supplemental) and the risk of gestational diabetes. METHODS: Serum samples from women with first trimester screening were linked to birth and hospital records for data on maternal characteristics and gestational diabetes diagnosis. Blood was analysed for ferritin, soluble transferrin receptor and C-reactive protein. Associations between iron biomarkers and gestational diabetes were assessed using multivariate logistic regression. A systematic review and meta-analysis, registered with PROSPERO (CRD42014013663) included studies of all designs published in English from January 1995 to July 2015 that examined the association between iron and gestational diabetes and included an appropriate comparison group. RESULTS: Of 3776 women, 3.4% subsequently developed gestational diabetes. Adjusted analyses found increased odds of gestational diabetes for ferritin (OR 1.41; 95% CI 1.11, 1.78), but not for soluble transferrin receptor (OR 1.00; 95% CI 0.97, 1.03) per unit increase of the biomarker. Two trials of iron supplementation found no association with gestational diabetes. Increased risk of gestational diabetes was associated with higher levels of ferritin and serum iron and dietary haem iron intakes. CONCLUSIONS: Increased risk of gestational diabetes among women with high serum ferritin and iron levels and dietary haem iron intakes warrants further investigation.


Assuntos
Proteína C-Reativa/metabolismo , Diabetes Gestacional/epidemiologia , Suplementos Nutricionais , Ferritinas/metabolismo , Ferro da Dieta/uso terapêutico , Receptores da Transferrina/metabolismo , Adulto , Diabetes Gestacional/metabolismo , Feminino , Humanos , Modelos Logísticos , Análise Multivariada , New South Wales/epidemiologia , Razão de Chances , Gravidez , Estudos Prospectivos , Fatores de Risco , Adulto Jovem
4.
Nature ; 466(7307): 727-9, 2010 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-20686568

RESUMO

To determine the influence of the environment on star formation, we need to study the process in the extreme conditions of massive young star clusters ( approximately 10(4) solar masses) near the centre of our own Galaxy. Observations must be carried out in the near infrared because of very high extinction in visible light within the Galactic plane. We need high resolution to identify cluster members from their peculiar motions, and because most such clusters span more than 1', efficient observation demands a wide field of view. There is at present no space-based facility that meets all these criteria. Ground-based telescopes can in principle make such observations when fitted with ground-layer adaptive optics (GLAO), which removes the optical aberration caused by atmospheric turbulence up to an altitude of approximately 500 m (refs 7-10). A GLAO system that uses multiple laser guide stars has been developed at the 6.5-m MMT telescope, in Arizona. In previous tests, the system improved the resolution of the telescope by 30-50%, limited by wavefront error in the optics, but that was insufficient to allow rapid determination of cluster membership. Here we report observations of the core of the globular cluster M3 made after commissioning a sensor to monitor and remove slowly varying aberration in the optics. In natural seeing of 0.7'', the point spread function at 2.2-mum wavelength was sharpened uniformly to 0.3'' over a field of at least 2'. The wide-field resolution was enhanced by a factor of two to three over previous work, with better uniformity, and extends to a wavelength of 1.2 mum. Entire stellar clusters may be examined in a single pointing, and cluster membership can be determined from two such observations separated by just one year.

5.
Eur J Cancer Care (Engl) ; 25(5): 753-63, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27255681

RESUMO

Data from registries at four major public hospitals in South Australia indicate increased 5-year disease-specific survivals for colorectal cancer from 48% to 63% between 1980-1986 and 2005-2010. For 80+ year olds, the increase was smaller, from 47% to 52%. Risk of case fatality halved overall, adjusting for age, gender, stage, differentiation and sub-site. Patients aged 80+ years had a lower risk reduction of about a third (hazards ratio: 0.69; 95% confidence limits, 0.52-0.92). Percentages having surgery and other specified treatments were lower for 80+ year olds than younger cases, although increases in treatment intensity occurred in this age range during 1980-2010, as seen in younger ages, in accordance with guidelines. The study illustrates the important feedback clinical registries can provide to clinicians on care patterns and outcomes in their hospital settings. Feedback can be the subject of local deliberations on how to achieve the best outcomes, including in the elderly by considering the best trade-offs between optimal cancer care and accommodations for co-morbidity and frailty. Clinical registry data can be used in comparative effectiveness research in local settings where there are sufficient case numbers.


Assuntos
Neoplasias do Colo/terapia , Neoplasias Retais/terapia , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Colo/mortalidade , Feminino , Hospitais Públicos/estatística & dados numéricos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Neoplasias Retais/mortalidade , Austrália do Sul
6.
Toxicol Appl Pharmacol ; 266(3): 439-42, 2013 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-23201461

RESUMO

Mustard gas, used in chemical warfare since 1917, is a mutagenic and carcinogenic agent that produces severe dermal lesions for which there are no effective therapeutics; it is currently seen as a potential terrorist threat to civilian populations. Sulforaphane, found in cruciferous vegetables, is known to induce enzymes that detoxify compounds such as the sulfur mustards that react through electrophilic intermediates. Here, we observe that a single topical treatment with sulforaphane induces mouse epidermal levels of the regulatory subunit of glutamate-cysteine ligase, the rate-limiting enzyme in glutathione biosynthesis, and also increases epidermal levels of reduced glutathione. Furthermore, a glutathione S-transferase, GSTA4, is also induced in mouse skin by sulforaphane. In an in vivo model in which mice are given a single mutagenic application of the sulfur mustard analog 2-(chloroethyl) ethyl sulfide (CEES), we now show that therapeutic treatment with sulforaphane abolishes the CEES-induced increase in mutation frequency in the skin, measured four days after exposure. Sulforaphane, a natural product currently in clinical trials, shows promise as an effective therapeutic against mustard gas.


Assuntos
Substâncias para a Guerra Química/toxicidade , Glutamato-Cisteína Ligase/biossíntese , Gás de Mostarda/análogos & derivados , Gás de Mostarda/toxicidade , Pele/efeitos dos fármacos , Tiocianatos/farmacologia , Animais , Indução Enzimática/efeitos dos fármacos , Feminino , Glutationa/biossíntese , Glutationa Transferase/biossíntese , Immunoblotting , Isotiocianatos , Camundongos , Camundongos Endogâmicos C57BL , Mutação , Pele/enzimologia , Pele/metabolismo , Sulfóxidos
7.
Toxicol Appl Pharmacol ; 263(2): 203-9, 2012 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-22732900

RESUMO

Sulfur mustard [bis(2-chloroethyl)sulfide, SM] is a well-known DNA-damaging agent that has been used in chemical warfare since World War I, and is a weapon that could potentially be used in a terrorist attack on a civilian population. Dermal exposure to high concentrations of SM produces severe, long-lasting burns. Topical exposure to high concentrations of 2-(chloroethyl) ethyl sulfide (CEES), a monofunctional analog of SM, also produces severe skin lesions in mice. Utilizing a genetically engineered mouse strain, Big Blue, that allows measurement of mutation frequencies in mouse tissues, we now show that topical treatment with much lower concentrations of CEES induces significant dose- and time-dependent increases in mutation frequency in mouse skin; the mutagenic exposures produce minimal toxicity as determined by standard histopathology and immunohistochemical analysis for cytokeratin 6 and the DNA-damage induced phosphorylation of histone H2AX (γ-H2AX). We attempted to develop a therapeutic that would inhibit the CEES-induced increase in mutation frequency in the skin. We observe that multi-dose, topical treatment with 2,6-dithiopurine (DTP), a known chemical scavenger of CEES, beginning 1h post-exposure to CEES, completely abolishes the CEES-induced increase in mutation frequency. These findings suggest the possibility that DTP, previously shown to be non-toxic in mice, may be useful as a therapeutic agent in accidental or malicious human exposures to SM.


Assuntos
Substâncias para a Guerra Química/toxicidade , Gás de Mostarda/análogos & derivados , Mutagênese/efeitos dos fármacos , Purinas/farmacologia , Pele/efeitos dos fármacos , Administração Cutânea , Animais , Dano ao DNA/efeitos dos fármacos , Relação Dose-Resposta a Droga , Feminino , Engenharia Genética , Histonas/efeitos dos fármacos , Histonas/metabolismo , Queratina-6/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Mutantes , Camundongos Transgênicos , Gás de Mostarda/administração & dosagem , Gás de Mostarda/toxicidade , Mutação , Fosforilação/efeitos dos fármacos , Pele/patologia , Fatores de Tempo
8.
Vet Pathol ; 49(1): 106-15, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22146851

RESUMO

A variety of 3-dimensional (3D) digital imaging modalities are available for whole-body assessment of genetically engineered mice: magnetic resonance microscopy (MRM), X-ray microcomputed tomography (microCT), optical projection tomography (OPT), episcopic and cryoimaging, and ultrasound biomicroscopy (UBM). Embryo and adult mouse phenotyping can be accomplished at microscopy or near microscopy spatial resolutions using these modalities. MRM and microCT are particularly well-suited for evaluating structural information at the organ level, whereas episcopic and OPT imaging provide structural and functional information from molecular fluorescence imaging at the cellular level. UBM can be used to monitor embryonic development longitudinally in utero. Specimens are not significantly altered during preparation, and structures can be viewed in their native orientations. Technologies for rapid automated data acquisition and high-throughput phenotyping have been developed and continually improve as this exciting field evolves.


Assuntos
Diagnóstico por Imagem/métodos , Imageamento Tridimensional/métodos , Camundongos Transgênicos , Fenótipo , Animais , Embrião de Mamíferos , Engenharia Genética , Humanos , Camundongos , Modelos Animais , Imagem Corporal Total/métodos
9.
Int J Oral Maxillofac Surg ; 51(3): 366-370, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34366208

RESUMO

The oropharyngeal throat pack is commonly used in oral and maxillofacial surgery despite debated evidence regarding its barrier function. The study objectives were to investigate whether the oropharyngeal pack reduces blood ingestion and to evaluate its relationship with postoperative nausea and vomiting (PONV) and throat pain. This was a single-center, parallel group, single-blind randomized controlled trial. Participants undergoing orthognathic surgery, age ≥16 years, were included in the study. After intubation and prior to surgery start, the treatment group received oropharyngeal packing; the control group received no packing. Outcome variables were the quality of gastric contents aspirated by nasogastric tube (bloody or not bloody), PONV, and throat pain (visual analog scale). Thirty patients (treatment n = 15; control n = 15) were randomized and analyzed. There was no difference between the groups in quality of gastric contents (P = 1.00) or incidence of PONV at 2 hours and 24 hours (P = 1.00). Throat pain incidence and severity at 2 hours were both higher in the treatment group, but this was not statistically significant (P = 0.128, P = 0.223). The results indicate that the oropharyngeal pack is not an effective barrier against blood ingestion. Oropharyngeal packs do not improve or worsen PONV, but may increase throat pain.


Assuntos
Cirurgia Ortognática , Faringe , Adolescente , Método Duplo-Cego , Ingestão de Alimentos , Humanos , Método Simples-Cego , Tampões Cirúrgicos
10.
Int J Oral Maxillofac Surg ; 51(2): 214-218, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33966966

RESUMO

The enhanced recovery after surgery (ERAS) protocol was designed to improve patient outcomes and decrease complications, opioid use, and postoperative nausea and vomiting (PONV). The aim of this retrospective cohort study was to examine the effectiveness of ERAS protocols implemented in orthognathic surgeries from 2017 to 2018 at the University of Alabama at Birmingham Hospital by measuring opioid use and PONV. Two groups were identified through chart review, a non-ERAS group (traditional) of patients who had surgery without a protocol and an ERAS group of patients who had surgery with the ERAS protocol. The anesthesia and surgical teams followed a standardized protocol for perioperative management. All procedures were performed by a single surgeon and included single- and double-jaw surgeries and adjunctive procedures. The patient charts were analyzed for postoperative opioid consumption (measured in morphine milligram equivalents, MME) and PONV. IBM SPSS Statistics version 26 was used to conduct the statistical analyses. The ERAS group received less opioids during the postoperative period than the control group (31.2 MME vs 54.6 MME, P= 0.002). The ERAS group also had a lower incidence of PONV, with 1.2 episodes of PONV compared to 2.4 episodes in the non-ERAS group (P= 0.008). This study demonstrates that the ERAS protocol is effective in decreasing postoperative opioid consumption and PONV.


Assuntos
Recuperação Pós-Cirúrgica Melhorada , Cirurgia Ortognática , Procedimentos Cirúrgicos Ortognáticos , Analgésicos Opioides/uso terapêutico , Humanos , Tempo de Internação , Dor Pós-Operatória , Náusea e Vômito Pós-Operatórios/epidemiologia , Náusea e Vômito Pós-Operatórios/prevenção & controle , Estudos Retrospectivos
11.
Nat Commun ; 13(1): 2159, 2022 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-35444239

RESUMO

Macular degeneration is a leading cause of blindness. Treatments to rescue vision are currently limited. Here, we study how loss of central vision affects lateral feedback to spared areas of the human retina. We identify a cone-driven gain control mechanism that reduces visual function beyond the atrophic area in macular degeneration. This finding provides an insight into the negative effects of geographic atrophy on vision. Therefore, we develop a strategy to restore this feedback mechanism, through activation of laterally projecting cells. This results in improved vision in Cnga3-/- mice, which lack cone function, as well as a mouse model of geographic atrophy. Our work shows that a loss of lateral gain control contributes to the vision deficit in macular degeneration. Furthermore, in mouse models we show that lateral feedback can be harnessed to improve vision following retinal degeneration.


Assuntos
Atrofia Geográfica , Degeneração Macular , Degeneração Retiniana , Animais , Atrofia Geográfica/genética , Atrofia Geográfica/terapia , Degeneração Macular/genética , Camundongos , Células Fotorreceptoras Retinianas Cones/fisiologia , Degeneração Retiniana/complicações , Degeneração Retiniana/genética , Degeneração Retiniana/terapia , Visão Ocular
12.
Neurobiol Dis ; 42(1): 48-54, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21220022

RESUMO

Absence-like seizures in the Genetic Absence Epilepsy Rats from Strasbourg (GAERS) model are believed to arise in hyperexcitable somatosensory cortical neurons, however the cellular basis of this increased excitability remains unknown. We have previously shown that expression of the Transmembrane AMPA receptor Regulatory Protein (TARP), stargazin, is elevated in the somatosensory cortex of GAERS. TARPs are critical regulators of the trafficking and function of AMPA receptors. Here we examine the developmental expression of stargazin and the impact this may have on AMPA receptor trafficking in the GAERS model. We show that elevated stargazin in GAERS is associated with an increase in AMPA receptor proteins, GluA1 and GluA2 in the somatosensory cortex plasma membrane of adult epileptic GAERS. Elevated stargazin expression is not seen in the epileptic WAG/Rij rat, which is a genetically distinct but phenotypically similar rat model also manifesting absence seizures, indicating that the changes seen in GAERS are unlikely to be a secondary consequence of the seizures. In juvenile (6 week old) GAERS, at the age when seizures are just starting to be expressed, there is elevated stargazin mRNA, but not protein expression for stargazin or the AMPA receptor subunits. In neonatal (7 day old) pre-epileptic GAERS there was no alteration in stargazin mRNA expression in any brain region examined. These data demonstrate that stargazin and AMPA receptor membrane targeting is altered in GAERS, potentially contributing to hyperexcitability in somatosensory cortex, with a developmental time course that would suggest a pathophysiological role in the epilepsy phenotype.


Assuntos
Canais de Cálcio/biossíntese , Epilepsia/genética , Neurônios/metabolismo , Receptores de AMPA/biossíntese , Córtex Somatossensorial/metabolismo , Animais , Canais de Cálcio/genética , Membrana Celular/genética , Membrana Celular/patologia , Membrana Celular/fisiologia , Modelos Animais de Doenças , Epilepsia/patologia , Epilepsia/fisiopatologia , Predisposição Genética para Doença , Neurônios/patologia , Neurônios/fisiologia , Fenótipo , Ratos , Ratos Mutantes , Receptores de AMPA/genética , Córtex Somatossensorial/patologia , Córtex Somatossensorial/fisiopatologia
13.
Acta Crystallogr Sect F Struct Biol Cryst Commun ; 67(Pt 10): 1179-83, 2011 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-22102022

RESUMO

Respiratory syncytial virus (RSV) is a frequent cause of respiratory illness in infants, but there is currently no vaccine nor effective drug treatment against this virus. The RSV RNA genome is encapsidated and protected by a nucleocapsid protein; this RNA-nucleocapsid complex serves as a template for viral replication. Interest in the nucleocapsid protein has increased owing to its recent identification as the target site for novel anti-RSV compounds. The crystal structure of human respiratory syncytial virus nucleocapsid (HRSVN) was determined to 3.6 Å resolution from two crystal forms belonging to space groups P2(1)2(1)2(1) and P1, with one and four decameric rings per asymmetric unit, respectively. In contrast to a previous structure of HRSVN, the addition of phosphoprotein was not required to obtain diffraction-quality crystals. The HRSVN structures reported here, although similar to the recently published structure, present different molecular packing which may have some biological implications. The positions of the monomers are slightly shifted in the decamer, confirming the adaptability of the ring structure. The details of the inter-ring contacts in one crystal form revealed here suggest a basis for helical packing and that the stabilization of native HRSVN is via mainly ionic interactions.


Assuntos
Proteínas do Nucleocapsídeo/química , Vírus Sincicial Respiratório Humano/química , Cristalografia por Raios X , Modelos Moleculares , Domínios e Motivos de Interação entre Proteínas , Estrutura Quaternária de Proteína , Estrutura Secundária de Proteína , RNA Viral/química
14.
Clin Oncol (R Coll Radiol) ; 33(1): 30-39, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32711920

RESUMO

AIMS: Skin toxicity is a common adverse effect of breast radiotherapy. We investigated whether inverse-planned intensity-modulated radiotherapy (IMRT) would reduce the incidence of skin toxicity compared with forward field-in-field breast IMRT (FiF-IMRT) in early stage breast cancer. MATERIALS AND METHODS: This phase III randomised controlled trial compared whole-breast irradiation with either FiF-IMRT or helical tomotherapy IMRT (HT-IMRT), with skin toxicity as the primary end point. Patients received 50 Gy in 25 fractions and were assessed to compare skin toxicity between treatment arms. RESULTS: In total, 177 patients were available for assessment and the median follow-up was 73.1 months. Inverse IMRT achieved more homogeneous coverage than FiF-IMRT; erythema and moist desquamation were higher with FiF-IMRT compared with HT-IMRT (61% versus 34%; P < 0.001; 33% versus 11%; P < 0.001, respectively). Multivariate analysis showed large breast volume, FiF-IMRT and chemotherapy were independent factors associated with worse acute toxicity. There was no difference between treatment arms in the incidence of late toxicities. The 5-year recurrence-free survival was 96.3% for both FiF-IMRT and HT-IMRT and the 5-year overall survival was 96.3% for FiF-IMRT and 97.4% for HT-IMRT. CONCLUSIONS: Our study showed significant reduction in acute skin toxicity using HT-IMRT compared with FiF-IMRT, without significant reduction in late skin toxicities. On the basis of these findings, inverse-planned IMRT could be used in routine practice for whole-breast irradiation with careful plan optimisation to achieve the required dose constraints for organs at risk.


Assuntos
Neoplasias da Mama , Efeitos Adversos de Longa Duração , Radiodermite , Radioterapia de Intensidade Modulada , Pele , Neoplasias da Mama/patologia , Neoplasias da Mama/radioterapia , Intervalo Livre de Doença , Feminino , Humanos , Efeitos Adversos de Longa Duração/diagnóstico , Efeitos Adversos de Longa Duração/etiologia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Radiodermite/diagnóstico , Radiodermite/etiologia , Radiodermite/prevenção & controle , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia de Intensidade Modulada/efeitos adversos , Radioterapia de Intensidade Modulada/métodos , Pele/patologia , Pele/efeitos da radiação
15.
Osteoarthritis Cartilage ; 18(3): 344-53, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19857510

RESUMO

OBJECTIVE: The goal of this study was to develop an algorithm to semi-automatically segment the meniscus in a series of magnetic resonance (MR) images to use for normal knees and those with moderate osteoarthritis (OA). METHOD: The segmentation method was developed then evaluated on 10 baseline MR images obtained from subjects with no evidence, symptoms, or risk factors of knee (OA), and 14 from subjects with established knee OA enrolled in the Osteoarthritis Initiative (OAI). After manually choosing a seed point within the meniscus, a threshold level was calculated through a Gaussian fit model. Under anatomical, intensity, and range constraints, a threshold operation was completed followed by conditional dilation and post-processing. The post-processing operation reevaluates the pixels included and excluded in the area surrounding the meniscus to improve accuracy. The developed method was evaluated for both normal and degenerative menisci by comparing the segmentation algorithm results with manual segmentations from five human readers. RESULTS: The semi-automated segmentation method produces results similar to those of trained observers, with an average similarity index over 0.80 for normal participants and 0.75, 0.67, and 0.64 for participants with established knee OA with Osteoarthritis Research Society International (OARSI) joint space narrowing (JSN) scores of 0, one, and two respectively. CONCLUSION: The semi-automatic segmentation method produced accurate and consistent segmentations of the meniscus when compared to manual segmentations in the assessment of normal menisci in mild to moderate OA. Future studies will examine the change in volume, thickness, and intensity characteristics at different stages of OA.


Assuntos
Cartilagem Articular/patologia , Meniscos Tibiais/patologia , Osteoartrite do Joelho/patologia , Algoritmos , Cartilagem Articular/diagnóstico por imagem , Estudos de Casos e Controles , Humanos , Joelho/diagnóstico por imagem , Joelho/patologia , Imageamento por Ressonância Magnética/métodos , Meniscos Tibiais/diagnóstico por imagem , Modelos Estatísticos , Osteoartrite do Joelho/diagnóstico por imagem , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Reprodutibilidade dos Testes , Índice de Gravidade de Doença
16.
Osteoarthritis Cartilage ; 18(11): 1436-40, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20813195

RESUMO

OBJECTIVE: To determine, in serial fixed-flexion (FF) radiographs of subjects with knee osteoarthritis (KOA), the importance of, and basis for, the effect of alignment of the medial tibial plateau (MTP), as determined by the inter-margin distance (IMD), on joint space narrowing (JSN). METHODS: Baseline and 12-month X-rays of 590 knees with Kellgren and Lawrence grade (KLG) 2/3 OA from the public-release dataset of the Osteoarthritis Initiative (OAI) were assigned to subgroups based upon IMD at baseline (IMD(BL)) and the difference between IMD(BL) and IMD(12 mos). Relationships of JSN to IMD(BL) and to the difference between IMD(BL and) IMD(12 mos) were evaluated. RESULTS: In all 590 knees, mean JSN was 0.13 ± 0.51 mm (P<0.0001) and MTP alignment and replication of IMD(BL) in the 12-month film were, in general, poor. JSN was significantly (P=0.012) more rapid in Subgroup A (IMD≤1.70 mm at both time points) than in Subgroup B (both IMDs>1.70 mm): 0.15 ± 0.43; 0.08 ± 0.47. Within Subgroup B we identified a subset, Subgroup B1, in which, although alignment was poor at both time points, the large IMD(BL) was, by chance, highly reproduced by IMD(12 mos) (difference between the two IMDs=0.01 ± 0.27 mm, NS). JSN in Subgroup B1 was 0.06 ± 0.41 mm and did not differ from that in other knees of Subgroup B (P=0.87). The standardized response mean (SRM) in all 590 knees and Subgroups A, B and B1 was 0.25, 0.34, 0.17 and 0.06, respectively. Independent of IMD(BL), JSN correlated significantly with the difference between the IMDs in the two radiographs (r=0.17, P=0.0001). CONCLUSION: Skewed MTP alignment in serial films and poor replication of IMD(BL) in the follow-up exam affect JSN measurement. The magnitude of change in joint space width (JSW) related to the poor quality of alignment that is common with the FF view jeopardizes accurate evaluation of JSN.


Assuntos
Articulação do Joelho/diagnóstico por imagem , Osteoartrite do Joelho/diagnóstico por imagem , Tíbia/diagnóstico por imagem , Idoso , Progressão da Doença , Métodos Epidemiológicos , Feminino , Humanos , Articulação do Joelho/patologia , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/patologia , Radiografia
17.
Chem Res Toxicol ; 23(3): 488-96, 2010 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-20050632

RESUMO

Sulfur mustard (bis-(2-chloroethyl)sulfide) has been used in chemical warfare since World War I and is well known as an acutely toxic vesicant. It has been implicated as a carcinogen after chronic low-level exposure and is known to form interstrand cross-links in DNA. Sulfur and nitrogen mustards are currently of interest as potential chemical threat agents for terrorists because of ease of synthesis. Sulfur mustard and monofunctional analogues (half-mustards, 2-[chloroethyl] alkyl sulfides) react as electrophiles, damaging cellular macromolecules, and thus are potentially subject to scavenging by nucleophilic agents. We have determined rate constants for the reaction of four purine derivatives that contain nucleophilic thiol moieties with several sulfur-half-mustards. Three of these compounds, 2,6-dithiopurine, 2,6-dithiouric acid, and 9-methyl-6-mercaptopurine, exhibit facile reaction with the electrophilic mustard compounds. At near neutral pH, these thiopurines are much better nucleophilic scavengers of mustard electrophiles than other low molecular weight thiols such as N-acetyl cysteine and glutathione. Progress curves calculated by numerical integration techniques indicate that equimolar concentrations of thiopurine provide significant reductions in the overall exposure to the episulfonium ions, which are the major reactive, electrophiles produced when sulfur mustards are dissolved in aqueous solution.


Assuntos
Substâncias para a Guerra Química/metabolismo , Gás de Mostarda/metabolismo , Purinas/farmacologia , Tionucleosídeos/farmacologia , Substâncias para a Guerra Química/química , Gás de Mostarda/análogos & derivados , Purinas/química , Tionucleosídeos/química
18.
Chem Res Toxicol ; 23(3): 497-503, 2010 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-20050631

RESUMO

Sulfur mustard (bis-(2-chloroethyl)sulfide) is a well-known chemical warfare agent that induces debilitating cutaneous toxicity in exposed individuals. It is also known to be carcinogenic and mutagenic because of its ability to damage DNA via electrophilic attack. We previously showed that a nucleophilic scavenger, 2,6-dithiopurine (DTP), reacts chemically with several electrophilic carcinogens, blocking DNA damage in vitro and in vivo and abolishing tumor formation in a two-stage mouse skin carcinogenesis model. To assess the potential of DTP as an antagonist of sulfur mustard, we have utilized monofunctional chemical analogues of sulfur mustard, 2-chloroethyl ethyl sulfide (CEES) and 2-chloroethyl methyl sulfide (CEMS), to induce toxicity and mutagenesis in a cell line, NCTC2544, derived from a human skin tumor. We show that DTP blocks cytotoxicity in CEMS- and CEES-treated cells when present at approximately equimolar concentration. A related thiopurine, 9-methyl-6-mercaptopurine, is similarly effective. Correlated with this, we find that DTP is transported into these cells and that adducts between DTP and CEES are found intracellularly. Using a shuttle vector-based mutagenesis system, which allows enumeration of mutations induced in the skin cells by a blue/white colony screen, we find that DTP completely abolishes the mutagenesis induced by CEMS and CEES in human cells.


Assuntos
Citotoxinas/efeitos adversos , Gás de Mostarda/análogos & derivados , Mutagênese/efeitos dos fármacos , Purinas/farmacologia , Pele/efeitos dos fármacos , Sulfetos/efeitos adversos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Humanos , Gás de Mostarda/efeitos adversos , Pele/citologia
19.
Bull Entomol Res ; 100(6): 671-8, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20482931

RESUMO

Grape phylloxera, Daktulosphaira vitifoliae Fitch, is an important pest of grapevines (Vitis vinifera L.) (Vitaceae). The distribution and frequency of phylloxera clone lineages vary within infested regions of Australia, suggesting the introduction of separate lineages of D. vitifoliae with host associations. Virulence levels of particular phylloxera clones may vary on V. vinifera, but much of this evidence is indirect. In this study, we directly tested the performance of phylloxera clones on V. vinifera using an established excised root assay and a new glasshouse vine assessment. In the root assay, grape phylloxera clones differed in egg production and egg to adult survivorship. In the vine assay, clones differed in the number of immature and adult life stages on roots. In addition vine characteristics, including mean stem weight, root weight, leaf chlorophyll and leaf area, were affected by different phylloxera clones. The two most widespread clones displayed high levels of virulence. These results point to only some phylloxera clones being highly virulent on V. vinifera, helping to explain patterns of field damage, phylloxera distributions and continued survival and production of V. vinifera vines in some infested areas.


Assuntos
Afídeos/fisiologia , Vitis/parasitologia , Animais , Células Clonais/fisiologia , Feminino , Oviposição/fisiologia , Folhas de Planta/parasitologia , Caules de Planta/parasitologia , Densidade Demográfica , Especificidade da Espécie , Análise de Sobrevida
20.
Science ; 276(5314): 939-42, 1997 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-9139655

RESUMO

X-ray emission was discovered in comet Hyakutake (C/1996 B2) by the Röntgen satellite in 1996, and these emissions were attributed to the excitation of high charge state solar wind ions due to electron capture from cometary molecules or atoms. Using the plasma flow in the coma of Hyakutake calculated by a three-dimensional adaptive magnetohydrodynamic model, the density distribution of solar wind ions in the coma and the resulting x-ray emission were computed. The calculated High Resolution Imager count rate of 4.4 per second and the spatial distribution of the x-ray emission agree with the observations. A detailed energy spectrum of cometary x-rays is predicted in the 80 to 2000 electronvolt energy range. Cometary x-rays present a sensitive tool to monitor cometary activity and solar wind ion composition.


Assuntos
Simulação por Computador , Íons , Meteoroides , Raios X , Carbono , Meio Ambiente Extraterreno , Hidrogênio , Neônio , Oxigênio
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