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1.
Ann Oncol ; 34(2): 200-211, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36423745

RESUMO

BACKGROUND: Post-treatment detection of circulating tumour DNA (ctDNA) in early-stage triple-negative breast cancer (TNBC) patients predicts high risk of relapse. c-TRAK TN assessed the utility of prospective ctDNA surveillance in TNBC and the activity of pembrolizumab in patients with ctDNA detected [ctDNA positive (ctDNA+)]. PATIENTS AND METHODS: c-TRAK TN, a multicentre phase II trial, with integrated prospective ctDNA surveillance by digital PCR, enrolled patients with early-stage TNBC and residual disease following neoadjuvant chemotherapy, or stage II/III with adjuvant chemotherapy. ctDNA surveillance comprised three-monthly blood sampling to 12 months (18 months if samples were missed due to coronavirus disease), and ctDNA+ patients were randomised 2 : 1 to intervention : observation. ctDNA results were blinded unless patients were allocated to intervention, when staging scans were done and those free of recurrence were offered pembrolizumab. A protocol amendment (16 September 2020) closed the observation group; all subsequent ctDNA+ patients were allocated to intervention. Co-primary endpoints were (i) ctDNA detection rate and (ii) sustained ctDNA clearance rate on pembrolizumab (NCT03145961). RESULTS: Two hundred and eight patients registered between 30 January 2018 and 06 December 2019, 185 had tumour sequenced, 171 (92.4%) had trackable mutations, and 161 entered ctDNA surveillance. Rate of ctDNA detection by 12 months was 27.3% (44/161, 95% confidence interval 20.6% to 34.9%). Seven patients relapsed without prior ctDNA detection. Forty-five patients entered the therapeutic component (intervention n = 31; observation n = 14; one observation patient was re-allocated to intervention following protocol amendment). Of patients allocated to intervention, 72% (23/32) had metastases on staging at the time of ctDNA+, and 4 patients declined pembrolizumab. Of the five patients who commenced pembrolizumab, none achieved sustained ctDNA clearance. CONCLUSIONS: c-TRAK TN is the first prospective study to assess whether ctDNA assays have clinical utility in guiding therapy in TNBC. Patients had a high rate of metastatic disease on ctDNA detection. Findings have implications for future trial design, emphasising the importance of commencing ctDNA testing early, with more sensitive and/or frequent ctDNA testing regimes.


Assuntos
Antineoplásicos Imunológicos , DNA Tumoral Circulante , Neoplasia Residual , Neoplasias de Mama Triplo Negativas , Humanos , Biomarcadores Tumorais/sangue , Mutação , Recidiva Local de Neoplasia/sangue , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/genética , Estudos Prospectivos , Neoplasias de Mama Triplo Negativas/sangue , Neoplasias de Mama Triplo Negativas/diagnóstico , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/genética , Neoplasia Residual/sangue , Neoplasia Residual/diagnóstico , Neoplasia Residual/tratamento farmacológico , Neoplasia Residual/genética , Antineoplásicos Imunológicos/uso terapêutico , DNA Tumoral Circulante/sangue
2.
Ann Chir Plast Esthet ; 68(3): 260-269, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36967309

RESUMO

Despite the frequency of paediatric hand injuries, recommendations for diagnostic investigations are limited due to paucity of published guidelines. This has led to inappropriate diagnoses and therefore inappropriate management. Ultrasonography is a portable, non-ionising imaging modality that allows rapid real-time evaluation of anatomical structures at a low cost and without sedation. In the adult population, ultrasonography has already been shown to improve accuracy in hand injury diagnoses. However, in the paediatric population, only one narrative review focuses on the application of ultrasonography to diagnose hand injury. A systematic search using PubMed, Google Scholar, EMBASE, Scopus, Cochrane database of systematic reviews and University Library of York, Keele, Edinburgh and King's College London was conducted to assess literature surrounding use of ultrasonography as a diagnostic tool for paediatric hand injuries. The literature search yielded 11,860 articles and 21 studies were identified with a total of 30 patients. Ultrasonography was observed to be an accurate tool for diagnosing bone, tendon, ligament and nerve injuries in children. The results of our study suggest that ultrasonography should be considered as an early diagnostic step for paediatric hand injuries.


Assuntos
Traumatismos da Mão , Adulto , Humanos , Criança , Ultrassonografia
3.
Ann Oncol ; 32(4): 488-499, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33385521

RESUMO

BACKGROUND: Palbociclib plus endocrine therapy (ET) is the standard treatment of hormone receptor-positive and human epidermal growth factor receptor 2-negative, metastatic breast cancer (MBC). However, its efficacy has not been compared with that of chemotherapy in a phase III trial. PATIENTS AND METHODS: PEARL is a multicentre, phase III randomised study in which patients with aromatase inhibitor (AI)-resistant MBC were included in two consecutive cohorts. In cohort 1, patients were randomised 1 : 1 to palbociclib plus exemestane or capecitabine. On discovering new evidence about estrogen receptor-1 (ESR1) mutations inducing resistance to AIs, the trial was amended to include cohort 2, in which patients were randomised 1 : 1 between palbociclib plus fulvestrant and capecitabine. The stratification criteria were disease site, prior sensitivity to ET, prior chemotherapy for MBC, and country of origin. Co-primary endpoints were progression-free survival (PFS) in cohort 2 and in wild-type ESR1 patients (cohort 1 + cohort 2). ESR1 hotspot mutations were analysed in baseline circulating tumour DNA. RESULTS: From March 2014 to July 2018, 296 and 305 patients were included in cohort 1 and cohort 2, respectively. Palbociclib plus ET was not superior to capecitabine in both cohort 2 [median PFS: 7.5 versus 10.0 months; adjusted hazard ratio (aHR): 1.13; 95% confidence interval (CI): 0.85-1.50] and wild-type ESR1 patients (median PFS: 8.0 versus 10.6 months; aHR: 1.11; 95% CI: 0.87-1.41). The most frequent grade 3-4 toxicities with palbociclib plus exemestane, palbociclib plus fulvestrant and capecitabine, respectively, were neutropenia (57.4%, 55.7% and 5.5%), hand/foot syndrome (0%, 0% and 23.5%), and diarrhoea (1.3%, 1.3% and 7.6%). Palbociclib plus ET offered better quality of life (aHR for time to deterioration of global health status: 0.67; 95% CI: 0.53-0.85). CONCLUSIONS: There was no statistical superiority of palbociclib plus ET over capecitabine with respect to PFS in MBC patients resistant to AIs. Palbociclib plus ET showed a better safety profile and improved quality of life.


Assuntos
Inibidores da Aromatase , Neoplasias da Mama , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Inibidores da Aromatase/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Capecitabina/uso terapêutico , Família de Proteínas EGF/uso terapêutico , Humanos , Piperazinas , Piridinas , Qualidade de Vida , Receptor ErbB-2/genética , Receptores de Estrogênio
4.
Epidemiol Infect ; 148: e13, 2020 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-32000879

RESUMO

In December 2016, Public Health England investigated an outbreak of campylobacteriosis in North West England, with 69 cases in total. Epidemiological, microbiological and environmental investigations associated the illness with the consumption of unpasteurised cows' milk from Farm X, where milk was predominantly sold from a vending machine. Campylobacter was detected in milk samples which, when sequenced, were identical in sequence type as pathogens isolated from cases (Clonal Complex ST-403, Sequence Type 7432). The farm was served with a Hygiene Emergency Prohibition Order to prevent further cases. To our knowledge, this is the first outbreak of campylobacter associated with unpasteurised milk in England since 1996. Our findings highlighted several important lessons, including that the current testing regime in England for unpasteurised milk is not fit for purpose and that the required warning label should include additional wording, underscoring the risk to vulnerable groups. There has been a substantial increase in both the volume of unpasteurised milk consumed in England and the use of vending machines to sell unpasteurised milk over the last 10 years, making unpasteurised milk more readily accessible to a wider population. The evidence generated from outbreaks like this is therefore critical and should be used to influence policy development.


Assuntos
Infecções por Campylobacter/epidemiologia , Campylobacter/isolamento & purificação , Surtos de Doenças , Contaminação de Alimentos , Doenças Transmitidas por Alimentos/epidemiologia , Leite/microbiologia , Adolescente , Adulto , Idoso , Animais , Campylobacter/classificação , Campylobacter/genética , Bovinos , Criança , Pré-Escolar , Inglaterra/epidemiologia , Feminino , Humanos , Lactente , Masculino , Técnicas Microbiológicas , Pessoa de Meia-Idade , Tipagem Molecular , Estudos Retrospectivos , Análise de Sequência de DNA , Adulto Jovem
5.
Epidemiol Infect ; 144(7): 1386-93, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-26567801

RESUMO

An anecdotal increase in C. perfringens outbreaks was observed in the North East of England during 2012-2014. We describe findings of investigations in order to further understanding of the epidemiology of these outbreaks and inform control measures. All culture-positive (>105 c.f.u./g) outbreaks reported to the North East Health Protection Team from 1 January 2012 to 31 December 2014 were included. Epidemiological (attack rate, symptom profile and positive associations with a suspected vehicle of infection), environmental (deficiencies in food preparation or hygiene practices and suspected vehicle of infection) and microbiological investigations are described. Forty-six outbreaks were included (83% reported from care homes). Enterotoxin (cpe) gene-bearer C. perfringens were detected by PCR in 20/46 (43%) and enterotoxin (by ELISA) and/or enterotoxigenic faecal/food isolates with indistinguishable molecular profiles in 12/46 (26%) outbreaks. Concerns about temperature control of foods were documented in 20/46 (43%) outbreaks. A suspected vehicle of infection was documented in 21/46 (46%) of outbreaks (meat-containing vehicle in 20/21). In 15/21 (71%) identification of the suspected vehicle was based on descriptive evidence alone, in 5/21 (24%) with supporting evidence from an epidemiological study and in 2/21 (10%) with supporting microbiological evidence. C. perfringens-associated illness is preventable and although identification of foodborne outbreaks is challenging, a risk mitigation approach should be taken, particularly in vulnerable populations such as care homes for the elderly.


Assuntos
Infecções por Clostridium/epidemiologia , Clostridium perfringens/fisiologia , Surtos de Doenças , Microbiologia de Alimentos , Doenças Transmitidas por Alimentos/epidemiologia , Infecções por Clostridium/microbiologia , Inglaterra/epidemiologia , Feminino , Doenças Transmitidas por Alimentos/microbiologia , Humanos , Masculino
6.
Lett Appl Microbiol ; 58(6): 535-40, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24461044

RESUMO

UNLABELLED: The Listeria genus comprises 10 recognized species. Listeria monocytogenes causes listeriosis in humans and other animals primarily via contaminated food or animal feed. Listeria ivanovii causes listeriosis in animals and on rare occasions in humans. The identification of nonpathogenic species of Listeria in foods indicates that conditions exist that support the growth of pathogenic strains and is used to facilitate the implementation of control and prevention measures. This study shows the development and evaluation of a 5'exonuclease real-time PCR assay for the rapid identification of Listeria seeligeri, Listeria welshimeri, L. monocytogenes, L. ivanovii, Listeria grayi and Listeria innocua. The assay consists of two triplexes that were evaluated using 53 cultures of Gram-positive bacteria, including 49 Listeria spp. from human, animal, food or food-processing environments. The assay was rapid, specific and reproducible and could identify each of the six species from a mixture of strains. The developed assay proved to be a powerful means of rapidly identifying Listeria species and could be usefully implemented in busy specialist reference laboratories. SIGNIFICANCE AND IMPACT OF THE STUDY: The identification of species of Listeria from foods is important to monitor pathogenic strains and facilitates the implementation of control measures. This study shows the development and evaluation of a 5'exonuclease real-time PCR assay for the rapid identification of L. seeligeri, L. welshimeri, L. monocytogenes and L. ivanovii, L. grayi, L. innocua. The developed assay proved to be specific, rapid and reproducible and therefore could be implemented in busy specialist reference laboratories.


Assuntos
Microbiologia de Alimentos , Listeria/genética , Animais , Humanos , Listeria/classificação , Tipagem Molecular , Reação em Cadeia da Polimerase Multiplex , Reação em Cadeia da Polimerase em Tempo Real , Reprodutibilidade dos Testes
7.
Front Microbiol ; 14: 1101205, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36846780

RESUMO

The COVID-19 pandemic brought about an urgent need to monitor the community prevalence of infection and detect the presence of SARS-CoV-2. Testing individual people is the most reliable method to measure the spread of the virus in any given community, but it is also the most expensive and time-consuming. Wastewater-based epidemiology (WBE) has been used since the 1960s when scientists implemented monitoring to measure the effectiveness of the Polio vaccine. Since then, WBE has been used to monitor populations for various pathogens, drugs, and pollutants. In August 2020, the University of Tennessee-Knoxville implemented a SARS-CoV-2 surveillance program that began with raw wastewater surveillance of the student residence buildings on campus, the results of which were shared with another lab group on campus that oversaw the pooled saliva testing of students. Sample collection began at 8 am, and the final RT-qPCR results were obtained by midnight. The previous day's results were presented to the campus administrators and the Student Health Center at 8 am the following morning. The buildings surveyed included all campus dormitories, fraternities, and sororities, 46 buildings in all representing an on-campus community of over 8,000 students. The WBE surveillance relied upon early morning "grab" samples and 24-h composite sampling. Because we only had three Hach AS950 Portable Peristaltic Sampler units, we reserved 24-h composite sampling for the dormitories with the highest population of students. Samples were pasteurized, and heavy sediment was centrifuged and filtered out, followed by a virus concentration step before RNA extraction. Each sample was tested by RT-qPCR for the presence of SARS-CoV-2, using the CDC primers for N Capsid targets N1 and N3. The subsequent pooled saliva tests from sections of each building allowed lower costs and minimized the total number of individual verification tests that needed to be analyzed by the Student Health Center. Our WBE results matched the trend of the on-campus cases reported by the student health center. The highest concentration of genomic copies detected in one sample was 5.06 × 107 copies/L. Raw wastewater-based epidemiology is an efficient, economical, fast, and non-invasive method to monitor a large community for a single pathogen or multiple pathogen targets.

8.
Front Microbiol ; 14: 1144026, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37187532

RESUMO

Introduction: Although severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) RNA has been frequently detected in sewage from many university dormitories to inform public health decisions during the COVID-19 pandemic, a clear understanding of SARS-CoV-2 RNA persistence in site-specific raw sewage is still lacking. To investigate the SARS-CoV-2 RNA persistence, a field trial was conducted in the University of Tennessee dormitories raw sewage, similar to municipal wastewater. Methods: The decay of enveloped SARS-CoV-2 RNA and non-enveloped Pepper mild mottle virus (PMMoV) RNA was investigated by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) in raw sewage at 4°C and 20°C. Results: Temperature, followed by the concentration level of SARS-CoV-2 RNA, was the most significant factors that influenced the first-order decay rate constants (k) of SARS-CoV-2 RNA. The mean k values of SARS-CoV-2 RNA were 0.094 day-1 at 4°C and 0.261 day-1 at 20°C. At high-, medium-, and low-concentration levels of SARS-CoV-2 RNA, the mean k values were 0.367, 0.169, and 0.091 day-1, respectively. Furthermore, there was a statistical difference between the decay of enveloped SARS-CoV-2 and non-enveloped PMMoV RNA at different temperature conditions. Discussion: The first decay rates for both temperatures were statistically comparable for SARS-CoV-2 RNA, which showed sensitivity to elevated temperatures but not for PMMoV RNA. This study provides evidence for the persistence of viral RNA in site-specific raw sewage at different temperature conditions and concentration levels.

9.
J R Army Med Corps ; 158(2): 85-95, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22860496

RESUMO

The liver is one of the commonest intra-abdominal organs injured worldwide in blunt and penetrating trauma and its management has evolved significantly in the last 30 years. Mandatory laparotomy has been replaced by an acceptance that for most blunt hepatic trauma, a selective non-operative approach is safe and effective with a failure rate ie the need to proceed to delayed laparotomy of approximately 10%. There is a markedly lower rate of complications in those that are managed non-operatively. Adjuncts to this conservative regimen such as angioembolisation and delayed laparoscopy to treat biliary peritonitis increase the chances of avoiding laparotomy. This belief in non-operative management has also been transferred to some degree to penetrating liver trauma, where there is a gradual accumulation of evidence to support this non-operative approach in a carefully selected group of patients. This article examines the evidence supporting the selective non-operative management of both blunt and penetrating liver trauma and describes the outcomes and complications.


Assuntos
Fígado/lesões , Ferimentos não Penetrantes/terapia , Ferimentos Penetrantes/terapia , Humanos , Escala de Gravidade do Ferimento , Fígado/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Ultrassonografia , Ferimentos não Penetrantes/diagnóstico , Ferimentos Penetrantes/diagnóstico
10.
eNeuro ; 9(3)2022.
Artigo em Inglês | MEDLINE | ID: mdl-35667848

RESUMO

As Huntington's disease (HD) progresses, there is a significant loss of neurons in the striatum in addition to a distinct thinning of the cerebral cortex. Despite an early presence of sensorimotor deficits in patients with HD, electrophysiological studies designed to assess the integrity of thalamocortical circuits are sparse. Using the R6/2 mouse model of HD, we provide evidence of reduced connectivity between thalamic cells and their targeted cortical regions. Whole-cell patch clamp recordings from ventral anterolateral nucleus (VAL; motor) and ventral posteromedial nucleus (VPM; somatosensory) thalamic neurons in ex vivo brain slices of R6/2 and wild-type (WT) mice revealed that cells in both thalamic nuclei of R6/2 mice exhibited significant differences in passive and active cell membrane properties (smaller cell membrane capacitances, faster decay time constants and increased input resistances) compared with WT cells. Although only cells in the VPM of symptomatic R6/2 mice had more depolarized resting membrane potentials compared with WTs, cells in both nuclei displayed increased excitability in symptomatic, but not presymptomatic, R6/2 mice. Optical activation of VAL and VPM terminals elicited smaller magnitude current responses in cortical pyramidal neurons (CPNs) in both motor cortex (M1CTX) and somatosensory barrel cortex (BCTX) of symptomatic R6/2 mice compared with CPNs in WT mice. Furthermore, we observed a decrease in the frequency of thalamocortical excitatory quantal events in R6/2 BCTX CPNs, with no genotype-dependent differences in AMPA:NMDA response amplitude ratios. These data suggest there is a decrease in the transmission of thalamocortical information that is likely because of impaired neurotransmitter release.


Assuntos
Doença de Huntington , Córtex Motor , Animais , Corpo Estriado , Modelos Animais de Doenças , Humanos , Doença de Huntington/genética , Camundongos , Camundongos Transgênicos , Técnicas de Patch-Clamp
11.
Microbiol Resour Announc ; 10(47): e0104921, 2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34817217

RESUMO

Reported here is a coding-complete genome sequence of a SARS-CoV-2 variant obtained from raw wastewater samples at the University of Tennessee-Knoxville campus. This sequence provides insight into SARS-CoV-2 variants that circulate on large college campuses but remain mostly undetected.

12.
Science ; 204(4400): 1415-7, 1979 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-17814200

RESUMO

The scanning multichannel microwave radiometer results for the Gulf of Alaska Seasat Experiment Workshop are quite encouraging, especially in view of the immaturity of the data-processing algorithms. For open ocean, rain-free cells of highest-quality surface truth wind determinations exhibit standard deviations of 3 meters per second about a bias of 1.5 meters per second. The sea-surface temperature shows a standard deviation of approximately 1.5 degrees C about a bias of 3 degrees to 5 degrees C under a variety of changing meteorological conditions.

13.
Science ; 245(4924): 1367-9, 1989 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-17798743

RESUMO

Images of Neptune obtained by the narrow-angle camera of the Voyager 2 spacecraft reveal large-scale cloud features that persist for several months or longer. The features' periods of rotation about the planetary axis range from 15.8 to 18.4 hours. The atmosphere equatorward of -53 degrees rotates with periods longer than the 16.05-hour period deduced from Voyager's planetary radio astronomy experiment (presumably the planet's internal rotation period). The wind speeds computed with respect to this radio period range from 20 meters per second eastward to 325 meters per second westward. Thus, the cloud-top wind speeds are roughly the same for all the planets ranging from Venus to Neptune, even though the solar energy inputs to the atmospheres vary by a factor of 1000.

14.
Lasers Med Sci ; 24(3): 405-9, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-18566851

RESUMO

Protective eye-wear which utilizes switched liquid crystal can provide protection for operators using intense pulsed light sources (IPLs). Such eye protection devices combine the properties of useful visual transmittance in the nonactivated state and low light transmission in the active blocking state. The performance of a specific LightSpeed device has been determined using a series of bandpass optical filters coupled to photodiode detectors with signals being captured using a USB interface. Such measurements have allowed key switching parameters of these devices to be determined as part of the process of assessing their effectiveness. Measurements of optical density of transmitting state and blocking state were also determined using a double grating spectroradiometer. A simple model of active filter function was developed and applied to specific IPL pulse profiles.


Assuntos
Dispositivos de Proteção dos Olhos , Lasers/efeitos adversos , Cristais Líquidos , Acidentes de Trabalho/prevenção & controle , Humanos , Saúde Ocupacional , Fenômenos Ópticos , Retina/lesões , Retina/efeitos da radiação
15.
J Antimicrob Chemother ; 62(2): 303-15, 2008 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-18467308

RESUMO

OBJECTIVES: The aim of this study was to investigate the persistence of Campylobacter species, strain types, antibiotic resistance and mechanisms of tetracycline resistance in poultry flocks treated with chlortetracycline. METHODS: Three commercially reared broiler flocks, naturally colonized with Campylobacter, were treated with chlortetracycline under experimental conditions. The numbers of Campylobacter isolated, and the species, flaA short variable region allele, and antimicrobial resistance of isolates were determined. RESULTS: For two of three flocks, tetracycline-resistant strains predominated prior to chlortetracycline exposure. Presence of the antibiotic had no discernible effect on the numbers or types of Campylobacter and the tetracycline-resistant strains persisted in numbers similar to those observed before treatment. With all flocks, some faecal samples were obtained that contained no Campylobacter, irrespective of exposure to chlortetracycline; this was more common as the birds grew older. For the third flock, tetracycline-resistant Campylobacter were in the minority of samples before and during exposure to chlortetracycline, but at sampling times after this, no resistant strains were found in the treated (or untreated) birds, irrespective of exposure to the antibiotic. All tetracycline-resistant isolates (MICs 16 to >128 mg/L) contained tet(O) and, for some isolates, this was transferable to Campylobacter jejuni 81116. The efflux pump inhibitor PAbetaN reduced the MICs of tetracycline for these isolates by 4-fold, suggesting that an intact efflux pump, presumably CmeABC, is required for high-level tetracycline resistance. CONCLUSIONS: Our data indicate that chlortetracycline treatment does not eradicate tetracycline-resistant Campylobacter spp. from poultry. However, if a low number of resistant isolates are present, then the antibiotic pressure appears insufficient to select such strains as the dominant population.


Assuntos
Antibacterianos/farmacologia , Campylobacter/efeitos dos fármacos , Clortetraciclina/farmacologia , Aves Domésticas/microbiologia , Resistência a Tetraciclina , Animais , Antibacterianos/administração & dosagem , Proteínas de Bactérias/genética , Transporte Biológico Ativo/efeitos dos fármacos , Campylobacter/classificação , Campylobacter/isolamento & purificação , Proteínas de Transporte/genética , Clortetraciclina/administração & dosagem , Contagem de Colônia Microbiana , DNA Bacteriano/genética , Dipeptídeos/farmacologia , Inibidores Enzimáticos/farmacologia , Fezes/microbiologia , Flagelina/genética , Transferência Genética Horizontal , Testes de Sensibilidade Microbiana
16.
Clin Pharmacol Ther ; 81(1): 83-7, 2007 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17186003

RESUMO

The vasoconstrictive action of angiotensin II (AII) is partly, sympathetically mediated and angiotensin-converting enzyme (ACE) inhibitors appear to exert a sympatholytic effect. We examine the effect of an orally administered, selective AT(1) receptor antagonist (losartan 50 mg) on sympathetically mediated vasoconstriction in healthy volunteers in an observer blind crossover study. Seven healthy, normotensive volunteers (21-32 years), were studied on two occasions at the end of each 6-week treatment period (losartan or placebo). Forearm blood flow (FABF) (ml/dl forearm/min) was measured by venous occlusion plethysmography during the application of lower body negative pressure (LBNP) (-20 cm H(2)O) and at the end of each incremental infusion of norepinephrine (60, 120, and 240 pmol/min). Comparison of blood flow changes was by repeated measures analysis of variance; P<0.05 was taken as statistically significant. Losartan did not alter blood pressure compared to placebo. It did significantly enhance LBNP-induced vasoconstriction in both the left arm compared to placebo (-36.6+/-3.4 vs -23.5+/-3.3%; P=0.017) and the right arm compared to placebo (-39.5+/-3.8 vs -21.0+/-3.6%; P=0.005). The FABF response to all doses of infused norepinephrine (60, 120, and 240 pmol/min) was also enhanced by losartan compared to placebo (-35.0+/-2.7 vs -18.2+/-6.0%; -43.6+/-4.3 vs -28.6+/-5.8%, and -53.9+/-3.2 vs -42.5+/-6.8%; P=0.057, respectively. Losartan enhances locally mediated sympathetic vasoconstriction in the forearm circulation of man, probably through its effect on circulating AII concentrations and we postulate that the adrenergic sympathetic constrictor action of AII is not mediated by the AT(1) receptor or is surmountable at this receptor.


Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Losartan/farmacologia , Vasoconstrição/efeitos dos fármacos , Sistema Vasomotor/efeitos dos fármacos , Adulto , Estudos Cross-Over , Relação Dose-Resposta a Droga , Antebraço/irrigação sanguínea , Humanos , Pressão Negativa da Região Corporal Inferior , Masculino , Norepinefrina/administração & dosagem , Norepinefrina/farmacologia , Pletismografia , Fluxo Sanguíneo Regional/efeitos dos fármacos , Vasoconstritores/administração & dosagem , Vasoconstritores/farmacologia
17.
Clin Oncol (R Coll Radiol) ; 19(5): 349-55, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17379487

RESUMO

AIMS: Computed tomography planning of whole breast radiotherapy (WBRT) improves breast coverage and reduces the normal tissue dose. Computed tomography planning may increase tumour bed boost treatment accuracy. The aims of this investigation were (1) to compare the breast boost volume treated with clinical mark-up with the volume delineated with computed tomography planning and (2) to study tumour bed volume changes between the initial planning computed tomography scan and a second computed tomography scan at the time of breast boost mark-up. MATERIALS AND METHODS: Women receiving adjuvant WBRT and an electron boost after breast-conserving surgery were eligible. As per standard practice, WBRT was computed tomography planned while the boost electron portal was clinically defined. Electron field borders were then traced with wire and a second computed tomography scan was carried out in the boost treatment position. Post-surgical radiological abnormalities were contoured to create a tumour bed clinical target volume (CTV) on both scans (CTV1 and CTV2). A 1cm margin to CTV2 defined the planning target volume (PTV). The proportions of the CTV2 and PTV receiving 90% (V90) and 80% (V80) of the dose were calculated. Changes in volume between CTV1 and CTV2 were analysed. RESULTS: Data from 47 eligible patients were analysed. The mean V90 for the PTV was 61%. Lower electron energy (P<0.001) and small field sizes (P=0.004) were associated with a low V90. The mean CTV decreased by 4.3 cm3 (P=0.014) and was smaller in those with a long surgery to computed tomography interval (P=0.008). On average, the 90% isodose covered 61 cm3 of normal tissue. CONCLUSIONS: Conventional clinical breast boost planning is inaccurate. Electron boost computed tomography planning together with appropriate surgical clip placement and the use of mammograms and pathological information should provide optimal coverage of the tumour site. The boost could usually be planned from the initial computed tomography scan.


Assuntos
Neoplasias da Mama/radioterapia , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador , Tomografia Computadorizada por Raios X , Adulto , Carcinoma in Situ/radioterapia , Elétrons , Feminino , Humanos , Pessoa de Meia-Idade , Radioterapia Adjuvante , Radioterapia de Intensidade Modulada
18.
Plant Dis ; 91(11): 1519, 2007 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30780775

RESUMO

The ectotrophic, root-infecting fungus Magnaporthe poae is the cause of summer patch of Kentucky bluegrass (Poa pratensis). The disease is widely distributed in the mid-Atlantic Region of the United States and west to central Nebraska and Kansas (2). It also has been found in certain locations of Washington and California (2) but has not been confirmed in the Rocky Mountain Region. In August 2005 and 2006, tan patches and rings of dead turf ranging from 10 to 30 cm in diameter were observed in Kentucky bluegrass swards in Grand Junction and Greeley, CO, respectively. The sites, separated by approximately 360 km, are located west and east of the Continental Divide. A network of ectotrophic hyphae were observed on diseased root segments collected from both sites. A fungus morphologically similar to M. poae (2) was consistently isolated from these segments. DNA was extracted from mycelium of one isolate from each location and amplified by PCR with the M. poae species-specific primers MP1 and MP2 (1). A 453-bp DNA fragment was consistently amplified from DNA of both isolates, diagnostic of M. poae. To our knowledge, this is the first report of summer patch in Colorado and indicates that M. poae may be widely distributed in the central Rocky Mountain Region. References: (1) T. E. Bunting et al. Phytopathology 86:398, 1996. (2) B. B. Clarke and A. B. Gould, eds. Turfgrass Patch Diseases Caused by Ectotrophic Root-Infecting Fungi. The American Phytopathological Society, St. Paul, MN, 1993.

19.
Postgrad Med J ; 82(970): 524-7, 2006 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-16891444

RESUMO

OBJECTIVE: To test the hypothesis that an acute increase in plasma homocysteine produced by methionine is associated with an acute increase in pulse wave velocity. DESIGN: A double blind, cross over, placebo controlled design was used and pulse wave velocity, plasma homocysteine, total cholesterol: high density lipoprotein ratio, plasma triglyceride, oxidised low density lipoprotein cholesterol concentrations, apolipoproteins A1 and B, and C reactive protein were measured between 12.5 and 20 hours after methionine loading or placebo. RESULTS: Between 12.5 and 20 hours after exposure to a methionine loading test, arterial pulse wave velocity showed no significant difference compared with placebo. At 12 hours after exposure to the methionine loading test, in the presence of a controlled diet, triglyceride concentration significantly increased by 32.6% (p<0.02), cholesterol: high density lipoprotein ratio increased significantly by 22.5% (p<0.05) compared with placebo. Simultaneously, systolic blood pressure increased significantly by 4.9% (p<0.02). CONCLUSION: In elderly volunteers, acute hyperhomocysteinaemia induced by methionine loading resulted in no overall significant delayed reduction in peripheral arterial distensibility. A significant deterioration in the lipid profile and increased blood pressure was seen during acute hyperhomocysteinaemia.


Assuntos
Homocisteína/metabolismo , Metionina/farmacologia , Idoso , Velocidade do Fluxo Sanguíneo/efeitos dos fármacos , Proteína C-Reativa/metabolismo , Complacência (Medida de Distensibilidade) , Estudos Cross-Over , Método Duplo-Cego , Interações Medicamentosas , Humanos , Lipídeos/sangue , Pessoa de Meia-Idade , Fluxo Pulsátil/efeitos dos fármacos , Fluxo Pulsátil/fisiologia
20.
Respir Med ; 99(2): 220-6, 2005 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-15715190

RESUMO

INTRODUCTION: Older patients are the most prevalent age cohort requiring bronchoscopy. Prior sedation should be offered to improve patient comfort and operator technical ease. Older patients have increased sensitivity to centrally acting drugs increasing the procedural risk. This perceived risk may limit access to bronchoscopy in older patients. There have been no systematic prospective placebo-controlled studies in older patients. We compared a novel premedication regimen-oral temazepam plus nebulised Lignocaine (new treatment) to an established regimen of intravenous alfentanyl (control). METHODS: Consecutive patients 75 years and older referred for bronchoscopy were considered. Twenty-five patients were randomly assigned to each group. The primary outcome measure was the lowest oxygen saturation recorded from the administration of IV drugs and for 30 min post-bronchoscopy. RESULTS: The lowest mean oxygen saturation in the new treatment group was 92.2% (90.3-94.2) and in the control group 91.1% (89.2-93.1). This was not statistically different (P = 0.370). There were no adverse events. CONCLUSION: This is the largest prospective study to date on an older population undergoing bronchoscopy supporting previous retrospective findings regarding the safety of this procedure. Determined by oxygen saturations there is no difference in safety between premedication regimens comprising oral temazepam/nebulised lignocaine or intravenous alfentanyl.


Assuntos
Broncoscopia/métodos , Lidocaína/uso terapêutico , Pneumopatias/diagnóstico , Dor/prevenção & controle , Temazepam/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Masculino , Satisfação do Paciente , Pré-Medicação/métodos , Estudos Prospectivos , Resultado do Tratamento
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