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1.
Radiother Oncol ; 196: 110326, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38735536

RESUMO

PURPOSE: The oxygen depletion hypothesis has been proposed as a rationale to explain the observed phenomenon of FLASH-radiotherapy (FLASH-RT) sparing normal tissues while simultaneously maintaining tumor control. In this study we examined the distribution of DNA Damage Response (DDR) markers in irradiated 3D multicellular spheroids to explore the relationship between FLASH-RT protection and radiolytic-oxygen-consumption (ROC) in tissues. METHODS: Studies were performed using a Varian Truebeam linear accelerator delivering 10 MeV electrons with an average dose rate above 50 Gy/s. Irradiations were carried out on 3D spheroids maintained under a range of O2 and temperature conditions to control O2 consumption and create gradients representative of in vivo tissues. RESULTS: Staining for pDNA-PK (Ser2056) produced a linear radiation dose response whereas γH2AX (Ser139) showed saturation with increasing dose. Using the pDNA-PK staining, radiation response was then characterised for FLASH compared to standard-dose-rates as a function of depth into the spheroids. At 4 °C, chosen to minimize the development of metabolic oxygen gradients within the tissues, FLASH protection could be observed at all distances under oxygen conditions of 0.3-1 % O2. Whereas at 37 °C a FLASH-protective effect was limited to the outer cell layers of tissues, an effect only observed at 3 % O2. Modelling of changes in the pDNA-PK-based oxygen enhancement ratio (OER) yielded a tissue ROC g0-value estimate of 0.73 ± 0.25 µM/Gy with a km of 5.4 µM at FLASH dose rates. CONCLUSIONS: DNA damage response markers are sensitive to the effects of transient oxygen depletion during FLASH radiotherapy. Findings support the rationale that well-oxygenated tissues would benefit more from FLASH-dose-rate protection relative to poorly-oxygenated tissues.

2.
Health Phys ; 124(2): 139-146, 2023 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-36508552

RESUMO

IMPORTANCE: 177 Lu therapy as part of theranostic treatment for cancer is expanding but it can be a challenge for sites with limited radiation protection staff to implement the radiation safety program required for therapeutic nuclear medicine. OBJECTIVE: To increase the adoption of 177 Lu therapy, especially in smaller centers and clinics, by providing a collection of radiation safety best practices and operational experience. To provide a resource for radiation safety officers supporting the implementation of a 177 Lu therapy program. METHODS: A panel of 11 radiation safety professionals representing sites across Canada and the United States with experience delivering 177 Lu therapy was assembled and discussed their responses to a list of questions focused on the following radiation safety topics: facility layout and design; radiation safety program; and drug management and patient care. RESULTS: A comprehensive set of best practice guidelines for clinical radiation safety during 177 Lu therapy has been developed based on the collective operational experience of a group of radiation safety professionals. Significant findings included that 177 Lu therapy is often safely administered in unshielded rooms, that staff radiation exposure associated with 177 Lu therapy is minimal relative to other nuclear medicine programs, and that some relatively simple preparation in advance including papering of common surfaces and planning for incontinence can effectively control contamination during therapy. CONCLUSION: The guidance contained in this paper will assist radiation safety professionals in the implementation of safe, effective 177 Lu therapy programs, even at smaller sites with limited to no experience in therapeutic nuclear medicine.


Assuntos
Medicina Nuclear , Proteção Radiológica , Humanos , Radioisótopos/efeitos adversos , Lutécio/uso terapêutico
3.
EJNMMI Phys ; 9(1): 2, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-35032234

RESUMO

BACKGROUND: Positron emission tomography (PET) with prostate specific membrane antigen (PSMA) have shown superior performance in detecting metastatic prostate cancers. Relative to [18F]fluorodeoxyglucose ([18F]FDG) PET images, PSMA PET images tend to visualize significantly higher-contrast focal lesions. We aim to evaluate segmentation and reconstruction algorithms in this emerging context. Specifically, Bayesian or maximum a posteriori (MAP) image reconstruction, compared to standard ordered subsets expectation maximization (OSEM) reconstruction, has received significant interest for its potential to reach convergence with minimal noise amplifications. However, few phantom studies have evaluated the quantitative accuracy of such reconstructions for high contrast, small lesions (sub-10 mm) that are typically observed in PSMA images. In this study, we cast 3 mm-16-mm spheres using epoxy resin infused with a long half-life positron emitter (sodium-22; 22Na) to simulate prostate cancer metastasis. The anthropomorphic Probe-IQ phantom, which features a liver, bladder, lungs, and ureters, was used to model relevant anatomy. Dynamic PET acquisitions were acquired and images were reconstructed with OSEM (varying subsets and iterations) and BSREM (varying ß parameters), and the effects on lesion quantitation were evaluated. RESULTS: The 22Na lesions were scanned against an aqueous solution containing fluorine-18 (18F) as the background. Regions-of-interest were drawn with MIM Software using 40% fixed threshold (40% FT) and a gradient segmentation algorithm (MIM's PET Edge+). Recovery coefficients (RCs) (max, mean, peak, and newly defined "apex"), metabolic tumour volume (MTV), and total tumour uptake (TTU) were calculated for each sphere. SUVpeak and SUVapex had the most consistent RCs for different lesion-to-background ratios and reconstruction parameters. The gradient-based segmentation algorithm was more accurate than 40% FT for determining MTV and TTU, particularly for lesions [Formula: see text] 6 mm in diameter (R2 = 0.979-0.996 vs. R2 = 0.115-0.527, respectively). CONCLUSION: An anthropomorphic phantom was used to evaluate quantitation for PSMA PET imaging of metastatic prostate cancer lesions. BSREM with ß = 200-400 and OSEM with 2-5 iterations resulted in the most accurate and robust measurements of SUVmean, MTV, and TTU for imaging conditions in 18F-PSMA PET/CT images. SUVapex, a hybrid metric of SUVmax and SUVpeak, was proposed for robust, accurate, and segmentation-free quantitation of lesions for PSMA PET.

4.
J Phys Chem Lett ; 11(14): 5446-5450, 2020 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-32584577

RESUMO

In a lithium/sulfur (Li/S) battery, the reduction of sulfur during discharge involves a particular mechanism, where the active material successively dissolves into the electrolyte to form lithium polysulfide intermediate species (Li2Sx), with x being a function of the state of charge. In this work, sulfur K-edge resonant inelastic X-ray scattering measurements were performed for the characterization of different Li2Sx polysulfide standard solutions. High-energy resolution fluorescence detected X-ray absorption spectroscopy allowed clear separation the pre-edge absorption peak corresponding to terminal sulfur atoms from the main absorption peak due to internal atoms and allowed quantitative evaluation of the evolution of the peak area ratio as a function of the polysulfide chain length. Results of this experimental work demonstrate that the normalized area of the pre-edge is a reliable fingerprint of the Li2Sx mean chain length in agreement with recent theoretical predictions. As a perspective, this work confirms that operando HERFD XAS can be used to differentiate mean polysulfide composition, which is key issue in the characterization of Li/S cells.

5.
Int J Radiat Oncol Biol Phys ; 102(5): 1560-1568, 2018 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-30071294

RESUMO

PURPOSE: To assess the effect of flattening-filter-free (FFF) and 10 MV radiation therapy beams on the peripheral dose received by a population of pediatric patients undergoing volumetric modulated arc therapy (VMAT). METHODS AND MATERIALS: Twenty-six previously delivered 6 MV flattened VMAT pediatric radiation therapy treatments plans were replanned with 6 MV flattened, 6 MV FFF, and 10 MV FFF VMAT. Monte Carlo simulation code EGSnrc was used in conjunction with a measurement-based model to obtain 3-dimensional dose distributions. Peripheral dose delivered by FFF beams was compared with that delivered by 6 MV flattened beams. A statistical analysis was performed to determine whether certain clinical factors (eg, target volume, location) were associated with a change in integral relative radiation dose. Neutron dose measurements assessed the neutron contribution from the 6 MV flattened and 10 MV FFF x-ray beams. RESULTS: Both the 6 MV FFF and 10 MV FFF beams delivered significantly lower peripheral radiation doses than 6 MV flattened (P < .01). The dose reduction was of 3.9% (95% confidence interval [CI] 2.1-5.7) and 9.8% (95% CI, 8.0-11.6) at 5 cm from the PTV and 21.9% (95% CI, 13.7-30.1) and 25.6% (95% CI, 17.6-33.6) at 30 cm for 6 MV FFF and 10 MV FFF beams, respectively. The clinical factors examined did not have a significant effect on the relative magnitude of the peripheral dose reduction. The upper limit on the neutron dose was determined to be 203 µSv for the 6 MV flattened and 522 µSv for the 10 MV FFF beam. CONCLUSIONS: Both FFF beams significantly (P < .01) reduced the peripheral dose. 10 MV FFF was more effective at reducing peripheral dose at distances <5 cm from the PTV edge. The neutron doses delivered by all beams were <1% compared with the photon doses. 10 MV FFF should be used to minimize peripheral dose.


Assuntos
Doses de Radiação , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia de Intensidade Modulada , Criança , Estudos de Coortes , Humanos , Método de Monte Carlo , Neoplasias/radioterapia , Imagens de Fantasmas , Dosagem Radioterapêutica
6.
Int J Surg Case Rep ; 48: 76-78, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29885916

RESUMO

INTRODUCTION: Massive splenomegaly is indicated by spleen weight exceeding 1000 g and largest spleen dimension greater than 20 cm Poulin et al. (1998). In many cases, splenectomy is the treatment of choice for massive splenomegaly because it releases the pressure on adjacent organs and also provides a definitive histopathological diagnosis of the underlying cause Iriyama et al. (2010), Radhakrishnan (2018). PRESENTATION OF CASE: Herein we present a clinical case of disseminated diffuse large B - cell lymphoma, clinical stage IV, with massive splenomegaly. A 53 - year old man complaining of unintentional major weight loss, palpable abdominal mass in the left hemiabdomen and cervical lymphadenopathy, was admited to Department of abdominal surgery, UMC Ljubljana. Abdominal CT scan showed massive spleen, enlarged retroperitoneal and upper mediastinal lymph nodes and cervical lymphadenopathy. Splenectomy was performed and spleen was sent on histological analysis. Operation and postoperative course were uneventful. Spleen specimen weighed 5034 g (6% of patient body weight) and measured 33 × 24 × 10 cm. Histological and immunohistochemical analysis set the diagnosis of diffuse large B - cell lymphoma. Patients received 5 cycluses of R-CHOP chemotherapy and 2 cycluses of prophylactic intrathecal chemotherapy postoperatively. DISCUSSION: Splenomegaly in combination with weight loss and malaise is very suggestive of underlying neoplastic condition and therefore requires further diagnostic investigations Han et al. (2008). Splenectomy in combination with adjuvant chemotherapy is the treatment of choice in case of spleen infiltration rith tumorous cells of B-cell lymphoma. However there are other possibilities in diagnosing and treatment of massive splenomegaly, including percutaneous image guided splenic needle biopsy and splenic artery embolisation prior to splenectomy. CONCLUSION: Our aim with this case report is to present splenectomy in conjuction with chemotherapy as a safe option of treatment for massive splenomegaly due to B-cell lymphoma infiltration.

8.
Euro Surveill ; 19(5)2014 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-24524234

RESUMO

The 2013/14 influenza season to date in Canada has been characterised by predominant (90%) A(H1N1)pdm09 activity. Vaccine effectiveness (VE) was assessed in January 2014 by Canada's sentinel surveillance network using a test-negative case-control design. Interim adjusted-VE against medically-attended laboratory-confirmed influenza A(H1N1)pdm09 infection was 74% (95% CI: 58-83). Relative to vaccine, A(H1N1)pdm09 viruses were antigenically similar and genetically well conserved, with most showing just three mutations across the 50 amino acids comprising antigenic sites of the haemagglutinin protein.


Assuntos
Vírus da Influenza A Subtipo H1N1/isolamento & purificação , Vacinas contra Influenza/administração & dosagem , Influenza Humana/epidemiologia , Influenza Humana/prevenção & controle , Vigilância de Evento Sentinela , Adolescente , Adulto , Idoso , Canadá/epidemiologia , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Testes de Inibição da Hemaglutinação , Humanos , Lactente , Vírus da Influenza A Subtipo H1N1/genética , Vírus da Influenza A Subtipo H1N1/imunologia , Vacinas contra Influenza/imunologia , Influenza Humana/diagnóstico , Influenza Humana/virologia , Nasofaringe/virologia , Nariz/virologia , Avaliação de Resultados em Cuidados de Saúde , Reação em Cadeia da Polimerase em Tempo Real , Estações do Ano , Sensibilidade e Especificidade , Análise de Sequência de DNA , Vacinação/estatística & dados numéricos
9.
Euro Surveill ; 18(49)2013 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-24330942

RESUMO

We describe a case of vaccine-associated measles in a two-year-old patient from British Columbia, Canada, in October 2013, who received her first dose of measles-containing vaccine 37 days prior to onset of prodromal symptoms. Identification of this delayed vaccine-associated case occurred in the context of an outbreak investigation of a measles cluster.


Assuntos
Vacina contra Sarampo-Caxumba-Rubéola/efeitos adversos , Sarampo/diagnóstico , Colúmbia Britânica , Canadá , Pré-Escolar , Exantema/etiologia , Exantema/virologia , Feminino , Febre/etiologia , Humanos , Sarampo/imunologia , Sarampo/prevenção & controle , Sarampo/virologia , Vacina contra Sarampo-Caxumba-Rubéola/administração & dosagem , Fatores de Tempo
10.
Euro Surveill ; 18(5)2013 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-23399422

RESUMO

The 2012/13 influenza season in Canada has been characterised to date by early and moderately severe activity, dominated (90%) by the A(H3N2) subtype. Vaccine effectiveness (VE) was assessed in January 2013 by Canada's sentinel surveillance network using a test-negative case-control design. Interim adjusted-VE against medically attended laboratory-confirmed influenza A(H3N2) infection was 45% (95% CI: 13-66). Influenza A(H3N2) viruses in Canada are similar to the vaccine, based on haemagglutination inhibition; however, antigenic site mutations are described in the haemagglutinin gene.


Assuntos
Vírus da Influenza A Subtipo H3N2/isolamento & purificação , Vacinas contra Influenza/administração & dosagem , Influenza Humana/epidemiologia , Influenza Humana/prevenção & controle , Vigilância de Evento Sentinela , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos Virais/análise , Canadá/epidemiologia , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Testes de Inibição da Hemaglutinação , Humanos , Vírus da Influenza A Subtipo H3N2/genética , Vírus da Influenza A Subtipo H3N2/imunologia , Vacinas contra Influenza/imunologia , Influenza Humana/diagnóstico , Influenza Humana/virologia , Masculino , Pessoa de Meia-Idade , Nasofaringe/virologia , Nariz/virologia , Médicos de Família , Reação em Cadeia da Polimerase , Análise de Sequência de DNA , Resultado do Tratamento
11.
Front Immunol ; 3: 87, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22586427

RESUMO

Most monoclonal antibodies (mAbs) generated from humans infected or vaccinated with the 2009 pandemic H1N1 (pdmH1N1) influenza virus targeted the hemagglutinin (HA) stem. These anti-HA stem mAbs mostly used IGHV1-69 and bound readily to epitopes on the conventional seasonal influenza and pdmH1N1 vaccines. The anti-HA stem mAbs neutralized pdmH1N1, seasonal influenza H1N1 and avian H5N1 influenza viruses by inhibiting HA-mediated fusion of membranes and protected against and treated heterologous lethal infections in mice with H5N1 influenza virus. This demonstrated that therapeutic mAbs could be generated a few months after the new virus emerged. Human immunization with the pdmH1N1 vaccine induced circulating antibodies that when passively transferred, protected mice from lethal, heterologous H5N1 influenza infections. We observed that the dominant heterosubtypic antibody response against the HA stem correlated with the relative absence of memory B cells against the HA head of pdmH1N1, thus enabling the rare heterosubtypic memory B cells induced by seasonal influenza and specific for conserved sites on the HA stem to compete for T-cell help. These results support the notion that broadly protective antibodies against influenza would be induced by successive vaccination with conventional influenza vaccines based on subtypes of HA in viruses not circulating in humans.

12.
J Virol Methods ; 172(1-2): 72-7, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21195111

RESUMO

Highly pathogenic avian influenza (HPAI) A(H5N1) strains have been causing sporadic cases of disease in South East Asia and Africa for many years. These cases are associated with a high fatality rate, and it is feared that the virus could evolve into a strain capable of causing a pandemic. It is likely that a requirement for a A(H5) pandemic to occur is a switch in the receptor affinity of the virus. Candidate mutations in the hemagglutinin glycoprotein have been identified in the literature, and their emergence in circulating viruses would be an ominous development. This study describes a method to identify the presence of these mutations, even within a quasispecies, using RT-PCR followed by in vitro translation and peptide characterization by MALDI-TOF mass spectrometry.


Assuntos
Virus da Influenza A Subtipo H5N1/genética , Virus da Influenza A Subtipo H5N1/metabolismo , Influenza Humana/virologia , Mutação , Receptores de Superfície Celular/metabolismo , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Sequência de Aminoácidos , Sítios de Ligação , Clonagem Molecular , DNA Complementar , Genoma Viral , Glicoproteínas de Hemaglutininação de Vírus da Influenza/química , Glicoproteínas de Hemaglutininação de Vírus da Influenza/genética , Glicoproteínas de Hemaglutininação de Vírus da Influenza/metabolismo , Humanos , Influenza Humana/diagnóstico , Dados de Sequência Molecular , Mutagênese Sítio-Dirigida , Ligação Proteica
13.
Parasitol Int ; 60(1): 25-33, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20887802

RESUMO

Tuna (Thunnus spp.) has been characterized by long distance migrations, highly predatory behavior and longevity, all of which in turn, enable infections with a wide spectrum of different parasitic groups, reflecting in a remarkable diversity of tuna parasite communities. Since 2003, we have been monitoring parasite communities of Atlantic bluefin tuna (Thunnus thynnus) that are caught from the wild and transferred into cages during spring-summer months, as well as assemblages in fish that exit rearing cycle during the winter harvest period after 1.5 years. Interestingly in reared tuna, parasitic populations exhibit a significant decreasing trend at the end of the rearing cycle, rarely observed in other intensive productions that represent a suitable environment for the emergence, establishment and transmission of pathogens. In order to assess epizootiological behavior of tuna parasites assemblages at the beginning (B group) and at the end (A group) of 1.5 year rearing cycle, we examined data on parasite prevalence and abundance over 4 years. The aim was to evaluate parasite diversity indices and emerging differences between newly caught and harvested fish, as well as community compositions and their nestedness in respect to the event in the rearing cycle (capture or harvest time). In order to be able to predict classification of tuna in two categories (newly caught or heavily infected and harvested or less infected fish), based on empirical didymozoids abundances and year of sampling, we built a decision tree model. Results suggest that specificities of parasite assemblages and their dynamics in tuna before and after farming have no similar precedents in aquaculture. A trend of parasitic pauperization repeating in each rearing cycle over four-years time, in once diverse and species rich parasite communities is observed, however, structures of both B and A group rearing assemblages remain nested, with the same species being core parasites (Didymosulcus katsuwonicola and Koellikerioides intestinalis). The B group exhibited significantly higher total parasite richness and mean parasites abundance, as well as the heteroxenous species richness and abundance in comparison to A group, where monoxenous species were not recorded at all. Eleven parasite species out of 26 taxa were selected as important in discriminating between B and A groups' parasites assemblages, while significantly the most abundant in B group were D. katsuwonicola, Platocystis alalongae, K. intestinalis, Koellikerioides internogastricus, Didymocystis abdominalis and Anisakis sp. It is hard to postulate the combination of factors affecting these parasite populations, but environmental, anthropogenic or host intrinsic influence has to be taken into account for further investigation.


Assuntos
Doenças dos Peixes/epidemiologia , Doenças dos Peixes/parasitologia , Parasitos/fisiologia , Atum/parasitologia , Animais , Biota , Pesqueiros , Análise Multivariada , Dinâmica Populacional , Prevalência
14.
Mol Cell Probes ; 24(6): 364-9, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20727404

RESUMO

Worldwide efforts are ongoing to improve influenza pandemic preparedness, including from the perspective of the clinical virology laboratory. In particular, much work has been devoted to the development of diagnostic assays targeted at the Highly Pathogenic Avian Influenza (HPAI) A(H5N1); much less efforts have been devoted to the A(H2) subtype. Yet, A(H2) subtype has a proven capacity to cause pandemics and is among the subtypes prioritized for surveillance and control. Although the human A(H2N2) virus that caused the pandemic of 1957 no longer circulates, many related avian A(H2) viruses circulate in avian population and could conceivably adapt to infect humans and cause a new pandemic. In this study the design and development of an RT-PCR assay specific for A(H2) subtype is presented. It is shown that the assay is highly sensitive and specific, able to detect human and avian A(H2) viruses, and can be incorporated into a multiplex assay with another previously described assay for HPAI A(H5N1).


Assuntos
Bioensaio/métodos , Vírus da Influenza A Subtipo H2N2/genética , Virus da Influenza A Subtipo H5N1/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Animais , Sequência de Bases , Aves/virologia , Primers do DNA/metabolismo , Humanos , Vírus da Influenza A Subtipo H2N2/isolamento & purificação , Virus da Influenza A Subtipo H5N1/isolamento & purificação , Influenza Aviária/epidemiologia , Influenza Aviária/virologia , Influenza Humana/epidemiologia , Influenza Humana/virologia , Dados de Sequência Molecular , Pandemias , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Alinhamento de Sequência , Análise de Sequência de DNA , Especificidade da Espécie , Sus scrofa/virologia
15.
J Hosp Infect ; 66(1): 40-5, 2007 May.
Artigo em Inglês | MEDLINE | ID: mdl-17350729

RESUMO

We evaluated the ability of ozone gas to inactivate Norovirus and its animal surrogate feline calicivirus (FCV) in dried samples placed at various locations within a hotel room, a cruise liner cabin and an office. Norovirus was measured by quantitative reverse transcriptase real-time polymerase chain reaction (QRT-PCR) assay, and FCV by a combination of QRT-PCR and virus infectivity assays. We were able to reduce the concentration of infectious FCV by a factor of more than 10(3), and in some cases beyond detection, under optimal conditions of ozone exposure with less than an hour of total operation. QRT-PCR assays indicated similar decreases in both viral RNAs. Virus-containing samples dried onto hard surfaces (plastic, steel and glass), and soft surfaces such as fabric, cotton and carpet, were equally vulnerable to the treatment. Our results show that Norovirus can be inactivated by exposure to ozone gas from a portable commercial generator in settings such as hotel rooms, cruise ship cabins and healthcare facilities.


Assuntos
Infecções por Caliciviridae/prevenção & controle , Desinfecção/métodos , Norovirus , Ozônio/farmacologia , Inativação de Vírus , Infecções Comunitárias Adquiridas/prevenção & controle , Infecção Hospitalar/prevenção & controle , Humanos , Norovirus/genética , Norovirus/patogenicidade , Reação em Cadeia da Polimerase Via Transcriptase Reversa
16.
J Virol Methods ; 139(2): 220-6, 2007 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-17118465

RESUMO

Concerns about emergence of a pandemic strain of influenza have been increasing. The strains of highly pathogenic influenza A(H5N1) currently circulating are considered among the most plausible candidates for giving rise to a pandemic strain. In this study the design and development of a RT-PCR assay specific for these highly pathogenic influenza A(H5) strains is presented. This is achieved in part by the design of a primer targeting the coding region for the protease cleavage site of the hemagglutinin, and another primer derived from a pan-hemagglutinin RT-PCR assay also presented in this study. It is shown that the HPAI A(H5) specific assay amplifies only the nucleic acids of highly pathogenic A(H5), with a high sensitivity.


Assuntos
Virus da Influenza A Subtipo H5N1/isolamento & purificação , Influenza Humana/diagnóstico , Técnicas de Amplificação de Ácido Nucleico/métodos , Animais , Aves , Primers do DNA , Humanos , Virus da Influenza A Subtipo H5N1/classificação , Virus da Influenza A Subtipo H5N1/genética , Virus da Influenza A Subtipo H5N1/patogenicidade , Influenza Aviária/diagnóstico , Influenza Aviária/virologia , RNA Viral/análise , RNA Viral/isolamento & purificação , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Sensibilidade e Especificidade
17.
Vaccine ; 25(15): 2842-51, 2007 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-17081662

RESUMO

INTRODUCTION: We report a case-control design using a sentinel physician network to estimate vaccine effectiveness (VE) against laboratory-confirmed, medically attended influenza (LC-MAI) and provide results for the 2005-2006 season of dual A and B vaccine mismatch in Canada. METHODS: Participants were patients >or=5 years of age presenting with influenza-like illness (ILI) to a sentinel physician in British Columbia, Canada between November 1, 2005 and April 30, 2006. Cases were participants in whom influenza was identified; controls tested negative for influenza A and B by PCR, R-mix and culture. Isolates were characterized by gene-sequencing and hemagglutination-inhibition (HI) assays. Odds ratios (OR) for LC-MAI in vaccinated versus non-vaccinated persons were derived with adjustment for age and chronic conditions. VE was estimated as [1-OR (vaccinated/unvaccinated)]. RESULTS: The sample included 442 patient visits: median age was 26 years, 10% were >or=65 years, 15% had a chronic condition and 22% received the 2005-2006 trivalent inactivated influenza vaccine >or=2 weeks before ILI onset. Two hundred and six participants were positive for influenza; 107 (52%) had influenza A/H3N2 and 99 (48%) had influenza B/Victoria lineage. Gene sequencing identified mutations away from the vaccine strain at key antigenic binding sites of the hemagglutinin (HA) protein of H3N2 isolates; the neuraminidase (NA) protein was conserved. Based on HI assays, three-quarters of influenza A and all B isolates were mismatched to the 2005-2006 vaccine. Point estimates for VE against LC-MAI were in the range of 50 to 70% for both types of influenza. CONCLUSION: 2005-2006 was the third consecutive season of vaccine mismatch based on varying HA for the A/H3N2 component and the third also for the B component since 2001. Vaccine mismatch resulted in diminished VE but substantial cross-protection. More timely detection of drift variants through gene sequencing of isolates facilitates interpretation of VE results. Since it may be more antigenically conserved, the vaccine content and contribution of NA to overall VE should be further evaluated for both A and B components. Infrastructure for real-time epidemiologic assessment of vaccine performance is important annually and in preparation for a pandemic.


Assuntos
Vírus da Influenza A Subtipo H3N2/isolamento & purificação , Vírus da Influenza B/isolamento & purificação , Vacinas contra Influenza/uso terapêutico , Influenza Humana/epidemiologia , Influenza Humana/prevenção & controle , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Canadá/epidemiologia , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Humanos , Influenza Humana/diagnóstico , Influenza Humana/virologia , Masculino , Pessoa de Meia-Idade , Médicos de Família , Vigilância de Evento Sentinela
18.
Can J Infect Dis Med Microbiol ; 18(4): 233-40, 2007 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-18923735

RESUMO

Accurate identification of persons with genital herpes is necessary for optimal patient management and prevention of transmission. Because of inherent inaccuracies, clinical diagnosis of genital herpes should be confirmed by laboratory testing for the causative agents herpes simplex virus type 1 (HSV-1) and HSV type 2 (HSV-2). Further identification of the HSV type is valuable for counselling on the natural history of infection and risk of transmission. Laboratory methods include antigen detection, culture, polymerase chain reaction (PCR) and conventional and type-specific serology (TSS). PCR has, by far, the greater sensitivity and should be the test of choice for symptomatic cases. HSV-2 TSS is indicated for patients with genital lesions in whom antigen detection, culture or PCR fail to detect HSV, and for patients who are asymptomatic but have a history suggestive of genital herpes. HSV-2 TSS is further indicated for patients infected with HIV. HSV-2 TSS along with HSV-1 TSS may be considered, as appropriate, in evaluating infection and/or immune status in couples discordant for genital herpes, women who develop their first clinical episode of genital herpes during pregnancy, asymptomatic pregnant women whose partners have a history of genital herpes or HIV infection, and women contemplating pregnancy or considering sexual partnership with those with a history of genital herpes. The above should be performed in conjunction with counselling of infected persons and their sex partners.

19.
Med Phys ; 33(1): 96-105, 2006 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-16485414

RESUMO

High precision techniques in radiation therapy, such as intensity modulated radiation therapy, offer the potential for improved target coverage and increased normal tissue sparing compared with conformal radiotherapy. The complex fluence maps used in many of these techniques, however, often lead to more challenging quality assurance with dose verification being labor-intensive and time consuming. A prototype dose verification system has been developed using a tissue equivalent plastic scintillator that provides easy-to-acquire, rapid, digital dose measurements in a plane perpendicular to the beam. The system consists of a water-filled Lucite phantom with a scintillator screen built into the top surface. The phantom contains a silver coated plastic mirror to reflect scintillation light towards a viewing window where it is captured using a charge coupled device camera and a personal computer. Optical photon spread is removed using a microlouvre optical collimator and by deconvolving a glare kernel from the raw images. A characterization of the system was performed that included measurements of linear output response, dose rate dependence, spatial linearity, effective pixel size, signal uniformity and both short- and long-term reproducibility. The average pixel intensity for static, regular shaped fields between 3 cm X 3 cm and 12 cm x 12 cm imaged with the system was found to be linear in the dose delivered with linear regression analysis yielding a correlation coefficient r2 > 0.99. Effective pixel size was determined to be 0.53 mm/pixel. The system was found to have a signal uniformity of 5.6% and a long-term reproducibility/stability of 1.7% over a 6 month period. The system's ability to verify a dynamic treatment field was evaluated using 60 degrees dynamic wedged fields and comparing the results to two-dimensional film dosimetry. Results indicate agreement with two-dimensional film dosimetry distributions within 8% inside the field edges. With further development, this system promises to provide a fast, directly digital, and tissue equivalent alternative to current dose verification systems.


Assuntos
Materiais Biomiméticos/efeitos da radiação , Plásticos/efeitos da radiação , Radiometria/instrumentação , Radioterapia Conformacional/instrumentação , Contagem de Cintilação/instrumentação , Desenho de Equipamento , Análise de Falha de Equipamento , Radiometria/métodos , Dosagem Radioterapêutica , Radioterapia Conformacional/métodos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
20.
J Appl Clin Med Phys ; 6(3): 63-80, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-16143792

RESUMO

This study compared the clinical functionality of BrainSCAN (BrainLAB) and Helios (Eclipse, Varian) for intensity-modulated radiation therapy (IMRT) treatment planning with the aim of identifying practical and technical issues. The study considered implementation and commissioning, dose optimization, and plan assessment. Both systems were commissioned for the same 6 MV photon beam equipped with a high-resolution multileaf collimator (Varian Millennium 120 leaf). The software was applied to three test plans having identical imaging and contour data. Analysis considered 3D axial dose distributions, dose-volume histograms, and monitor unit calculations. Each system requires somewhat different input data to characterize the beam prior to use, so the same data cannot be used for commissioning. In addition, whereas measured beam data was entered directly into Helios with minimal data processing, the BrainSCAN system required configured beam data to be sent to BrainLAB before clinical use. One key difference with respect to system commissioning was that BrainSCAN required high resolution data, which necessitated the use of detectors with small active volumes. This difference was found to impact on the ability of the systems to accurately calculate dose for highly modulated fields, with BrainSCAN being more successful than Helios. In terms of functionality, the BrainSCAN system uses a dynamically penalized likelihood inverse planning algorithm and calculates four plans at once with various relative weighting of the planning target and organ-at-risk volumes. Helios uses a gradient algorithm that allows the user to make changes to some of the input parameters during optimization. An analysis of the dosimetry output shows that, although the systems are different in many respects, they are each capable of producing substantially equivalent dose plans in terms of target coverage and normal tissue sparing.


Assuntos
Algoritmos , Radiometria/métodos , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia Conformacional/métodos , Software , Dosagem Radioterapêutica , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Validação de Programas de Computador
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