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1.
Nature ; 593(7860): 548-552, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33882562

RESUMO

Global peatlands store more carbon than is naturally present in the atmosphere1,2. However, many peatlands are under pressure from drainage-based agriculture, plantation development and fire, with the equivalent of around 3 per cent of all anthropogenic greenhouse gases emitted from drained peatland3-5. Efforts to curb such emissions are intensifying through the conservation of undrained peatlands and re-wetting of drained systems6. Here we report eddy covariance data for carbon dioxide from 16 locations and static chamber measurements for methane from 41 locations in the UK and Ireland. We combine these with published data from sites across all major peatland biomes. We find that the mean annual effective water table depth (WTDe; that is, the average depth of the aerated peat layer) overrides all other ecosystem- and management-related controls on greenhouse gas fluxes. We estimate that every 10 centimetres of reduction in WTDe could reduce the net warming impact of CO2 and CH4 emissions (100-year global warming potentials) by the equivalent of at least 3 tonnes of CO2 per hectare per year, until WTDe is less than 30 centimetres. Raising water levels further would continue to have a net cooling effect until WTDe is within 10 centimetres of the surface. Our results suggest that greenhouse gas emissions from peatlands drained for agriculture could be greatly reduced without necessarily halting their productive use. Halving WTDe in all drained agricultural peatlands, for example, could reduce emissions by the equivalent of over 1 per cent of global anthropogenic emissions.

2.
Clin Radiol ; 78(6): e477-e485, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36958956

RESUMO

AIM: To explain the design and delivery of diagnostic imaging and image-guided intervention services for an international games. The authors share their experiences from the Birmingham Commonwealth Games 2022. MATERIALS AND METHODS: A retrospective analysis was undertaken of anonymised data from the Zillion, Easyvision (RIS and PACS), and Encounter platforms for image viewing, interpretation and reporting during the Games. The data collected included age and gender, type of sport, nature of the injury, and imaging findings with diagnoses. RESULTS: The number of individuals who had radiological investigations at the Birmingham Commonwealth Games was 518 and the vast majority of them were athletes (90 %). The average age of athletes who had imaging was 28 years and that of non-athletes who accessed imaging services was 46.4 years with male predominance. Magnetic resonance imaging was the most frequently used imaging technique and the lower limb was the most frequently imaged body part. Athletes playing netball and beach volleyball had the highest percentage of injuries. CONCLUSION: The authors share their experience from the Birmingham Commonwealth Games 2022 regarding the nuances and challenges in radiology service provision for an international sports event that would be helpful for musculoskeletal radiologists in the design and delivery of similar international events in the future.


Assuntos
Traumatismos em Atletas , Esportes , Masculino , Humanos , Adulto , Feminino , Estudos Retrospectivos , Atletas , Imageamento por Ressonância Magnética
3.
J Helminthol ; 94: e105, 2019 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-31735179

RESUMO

The superfamily Pronocephaloidea Looss, 1899 comprises digeneans occurring in the gut and respiratory organs of fishes, turtles, marine iguanas, birds and mammals. Although many life cycles are known for species of the Notocotylidae Lühe, 1909 maturing in birds and mammals, relatively few are known for the remaining pronocephaloid lineages. We report the cercariae of five pronocephaloid species from marine gastropods of the Queensland coast, Australia. From Lizard Island, northern Great Barrier Reef, we report three cercariae, two from Rhinoclavis vertagus (Cerithiidae) and one from Nassarius coronatus (Nassariidae). From Moreton Bay, southern Queensland, an additional two cercariae are reported from two genotypes of the gastropod worm shell Thylacodes sp. (Vermetidae). Phylogenetic analysis using 28S rRNA gene sequences shows all five species are nested within the Pronocephaloidea, but not matching or particularly close to any previously sequenced taxon. In combination, phylogenetic and ecological evidence suggests that most of these species will prove to be pronocephalids parasitic in marine turtles. The Vermetidae is a new host family for the Pronocephaloidea.


Assuntos
Gastrópodes/parasitologia , Filogenia , Trematódeos/anatomia & histologia , Trematódeos/classificação , Animais , Organismos Aquáticos/classificação , Organismos Aquáticos/parasitologia , Cercárias/anatomia & histologia , Cercárias/classificação , Cercárias/isolamento & purificação , DNA Intergênico/genética , Gastrópodes/classificação , Genótipo , Estágios do Ciclo de Vida , Queensland , RNA Ribossômico 28S/genética , Trematódeos/isolamento & purificação
4.
Ann Oncol ; 28(10): 2581-2587, 2017 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-28961848

RESUMO

BACKGROUND: The BRIM-3 trial showed improved progression-free survival (PFS) and overall survival (OS) for vemurafenib compared with dacarbazine in treatment-naive patients with BRAFV600 mutation-positive metastatic melanoma. We present final OS data from BRIM-3. PATIENTS AND METHODS: Patients were randomly assigned in a 1 : 1 ratio to receive vemurafenib (960 mg twice daily) or dacarbazine (1000 mg/m2 every 3 weeks). OS and PFS were co-primary end points. OS was assessed in the intention-to-treat population, with and without censoring of data for dacarbazine patients who crossed over to vemurafenib. RESULTS: Between 4 January 2010 and 16 December 2010, a total of 675 patients were randomized to vemurafenib (n = 337) or dacarbazine (n = 338, of whom 84 crossed over to vemurafenib). At the time of database lock (14 August 2015), median OS, censored at crossover, was significantly longer for vemurafenib than for dacarbazine {13.6 months [95% confidence interval (CI) 12.0-15.4] versus 9.7 months [95% CI 7.9-12.8; hazard ratio (HR) 0.81 [95% CI 0.67-0.98]; P = 0.03}, as was median OS without censoring at crossover [13.6 months (95% CI 12.0-15.4) versus 10.3 months (95% CI 9.1-12.8); HR 0.81 (95% CI 0.68-0.96); P = 0.01]. Kaplan-Meier estimates of OS rates for vemurafenib versus dacarbazine were 56% versus 46%, 30% versus 24%, 21% versus 19% and 17% versus 16% at 1, 2, 3 and 4 years, respectively. Overall, 173 of the 338 patients (51%) in the dacarbazine arm and 175 of the 337 (52%) of those in the vemurafenib arm received subsequent anticancer therapies, most commonly ipilimumab. Safety data were consistent with the primary analysis. CONCLUSIONS: Vemurafenib continues to be associated with improved median OS in the BRIM-3 trial after extended follow-up. OS curves converged after ≈3 years, likely as a result of crossover from dacarbazine to vemurafenib and receipt of subsequent anticancer therapies. CLINICALTRIALS.GOV: NCT01006980.


Assuntos
Indóis/uso terapêutico , Melanoma/tratamento farmacológico , Mutação , Proteínas Proto-Oncogênicas B-raf/genética , Neoplasias Cutâneas/tratamento farmacológico , Sulfonamidas/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Antineoplásicos Alquilantes/uso terapêutico , Dacarbazina/uso terapêutico , Inibidores Enzimáticos/uso terapêutico , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Melanoma/enzimologia , Melanoma/genética , Melanoma/mortalidade , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas B-raf/antagonistas & inibidores , Neoplasias Cutâneas/enzimologia , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/mortalidade , Resultado do Tratamento , Vemurafenib , Adulto Jovem
5.
Intern Med J ; 47(1): 57-61, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27572474

RESUMO

BACKGROUND: It has been suggested that environmental pollution from an earthquake might be associated with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). AIM: To determine the incidence of AAV during the 3-year period before (period 1), and the 3 years following (period 2), the earthquake that occurred on 22 February 2011 in Christchurch, New Zealand. METHODS: All ANCA tests performed in the Canterbury region for 3 years before the earthquake (period 1, 2007-2010), and for 3 years after the earthquake (period 2, 2011-2014) were examined. AAV was defined according to The European Medicines Agency classification algorithm. Medical records were reviewed and cases were included if they were newly diagnosed within the study period. Incidence was calculated using population data from the 2013 New Zealand census. RESULTS: A total of 52 new cases of AAV was identified. The incidence in period 1 was 1.87/100 000/annum (95% C.I. 1.23-2.72), and for period 2 was 1.73/100 000/annum (95% C.I. 1.12-2.55). There was no statistically significant difference in incidence between the two study periods. There was no difference when analysing by myeloperoxidase (MPO) or proteinase-3 status, or restricting the analyses to those residing in an urban environment. The mean age at diagnosis for MPO AAV was significantly younger in period 2 than period 1 (61 years vs 71 years, P = 0.05). There were no other clinically important differences between the two groups. CONCLUSION: This study does not support the hypothesis that an environmental agent, caused by dust pollution related to earthquake damage, has a causative role in the pathogenesis of AAV.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/epidemiologia , Anticorpos Anticitoplasma de Neutrófilos/sangue , Desastres , Terremotos , Adulto , Idoso , Idoso de 80 Anos ou mais , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/diagnóstico , Feminino , Humanos , Incidência , Lactente , Masculino , Pessoa de Meia-Idade , Nova Zelândia/epidemiologia
6.
Nat Genet ; 11(4): 441-3, 1995 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-7493027

RESUMO

The human skin is a complex organ composed of the surface epidermis, the subjacent dermis (in which blood vessels, lymphatics and nerves are located) and the skin appendages. The latter include hair follicles, sebaceous glands (which secrete lipids that may serve as a permeability barrier, emollient or antimicrobial agent), apocrine glands (which secrete scents) and eccrine glands (which produce sweat for temperature control). Hereditary cylindromatosis (MIM 123850) is a rare autosomal dominant disease characterised by the development of multiple neoplasms originating from the skin appendages. These neoplasms have been termed cylindromas due to their characteristic microscopic architecture and are believed to exhibit apocrine or eccrine differentiation. We have carried out a genome search using two families with this disease, which has provided strong evidence for linkage of cylindromatosis to loci on chromosome 16q12-q13. Using markers close to the cylindromatosis gene, consistent loss of the wild-type allele was observed in 19 tumours from four individuals in the two families, indicating that the gene is likely to be a tumour suppressor gene.


Assuntos
Carcinoma Adenoide Cístico/genética , Mapeamento Cromossômico , Cromossomos Humanos Par 16 , Genes Supressores de Tumor , Neoplasias Cutâneas/genética , Feminino , Genes Neoplásicos , Haplótipos , Humanos , Escore Lod , Masculino , Repetições de Microssatélites , Linhagem
7.
Ann Oncol ; 23(3): 577-582, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21821550

RESUMO

BACKGROUND: Melanoma frequently metastasizes to the lung. Improved radiologic techniques may decrease the need for biopsy of such lesions. The aim of this study was to examine factors predictive of a positive biopsy of melanoma. METHODS: Using the Memorial Sloan-Kettering Cancer Center melanoma database, all patients with melanoma who had undergone biopsy of a suspicious new lung lesion from 1996 to 2009 were identified. Age, date of diagnosis, histology, and stage were obtained. Chart review was carried out to obtain medical history, smoking status, radiological appearance, and histology of lung lesions biopsied. RESULTS: Two hundred and twenty-nine patients were identified; median age was 63 years; 48% were never smokers; 27% had a prior nonmelanoma cancer; 88% of lung nodules were malignant: 69% melanoma, 19% other cancers. Among 113 patients undergoing positron emission tomography (PET), proportions of benign, melanoma, and nonmelanoma 2-[fluorine-18]fluoro-2-deoxy-D-glucose-avid nodules did not differ (P = 0.53). On multivariable analysis, >stage I melanoma, negative smoking history, multiple lung nodules, and no prior nonmelanoma cancer were significantly associated with a melanoma biopsy result rather than other cancer. CONCLUSIONS: In this study, 31% of lung lesions were not melanoma. In the subset undergoing PET, this did not differentiate between benign and malignant lesions. Biopsy is mandated in melanoma patients with new lung nodules.


Assuntos
Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/secundário , Melanoma/diagnóstico , Melanoma/secundário , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Bases de Dados Factuais , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/mortalidade , Masculino , Melanoma/mortalidade , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons , Modelos de Riscos Proporcionais , Adulto Jovem
8.
Intern Med J ; 42(4): e23-6, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22498132

RESUMO

Our aim was to describe the treatment and survival characteristics of Wegener's granulomatosis (WG) in Canterbury, New Zealand. The medical records of 48 patients diagnosed between 1 July 1997 and 31 December 2008 and fulfilling validated classification criteria for WG were reviewed to characterise survivorship in the province of Canterbury, New Zealand. The age at diagnosis was 61 years (range 20 to 83 years) with an equal number of males and females. Using Kaplan-Meier product-limit analysis, the probability of survival at 1 and 10 years was 91% and 62% respectively. Of the 12 deaths in the cohort, four occurred within 12 months of diagnosis: two from pulmonary haemorrhage and two from renal failure. Beyond 12 months, two patients died of renal failure, two of myocardial infarction and one from cardiac arrhythmia, one from cerebrovascular disease and two from colorectal carcinoma. The median time to relapse was 6.75 years, and the probability of relapse within 10 years was 67%. Survivorship, treatment response rate and the rate of relapse from WG in a cohort of patients from this high-prevalence southern hemisphere region were similar to that reported for northern hemisphere cohorts with a similar prevalence.


Assuntos
Granulomatose com Poliangiite/tratamento farmacológico , Granulomatose com Poliangiite/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Granulomatose com Poliangiite/mortalidade , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Nova Zelândia/epidemiologia , Prevalência , Prognóstico , Taxa de Sobrevida , Resultado do Tratamento
9.
Eur J Appl Physiol ; 112(5): 1817-25, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-21915700

RESUMO

The purpose of this study was to examine the effect of exercise and pre-exercise dietary manipulation on hepatic triglyceride concentration (HTGC). HTGC was measured by proton magnetic resonance spectroscopy ((1)H-MRS) before and after 90 min of moderate intensity cycling in six endurance trained males following 67 h of mixed diet (M) and an isocaloric minimal carbohydrate (2%) high fat (83%) diet (HF). Diets were administered by balanced crossover design. Whole-body fat oxidation, plasma-free fatty acid (FFA), glycerol and triglyceride concentrations were significantly elevated during exercise in HF versus M (P < 0.05 for all). There was no significant treatment × time interaction for HTGC (P = 0.368). However, there was a significant net increase in HTGC (time effect) during the combined 6 h exercise and post-exercise period (P = 0.037). In conclusion, we observed no measurable net change in the hepatic triglyceride pool across a period involving a prolonged exercise bout. Furthermore, manipulation of pre-exercise dietary intake did not influence the interaction between the hepatic triglyceride concentration and exercise in lean trained men. This supports the contention that hepatic triglycerides do not meaningfully contribute to the high rate of fat oxidation observed during acute exercise, or the enhancement of this with regular exercise training and/or pre-exercise dietary manipulation.


Assuntos
Dieta , Exercício Físico/fisiologia , Ácidos Graxos não Esterificados/sangue , Fígado/metabolismo , Resistência Física/fisiologia , Triglicerídeos/metabolismo , Adulto , Ciclismo/fisiologia , Calorimetria Indireta , Estudos Cross-Over , Humanos , Espectroscopia de Ressonância Magnética , Masculino
10.
J Environ Manage ; 101: 92-103, 2012 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-22406849

RESUMO

Discolouration of natural surface waters due to the humic component of dissolved organic carbon (DOC) is a costly problem for water supply companies. This paper reviews what is known about the impacts of prescribed moorland vegetation burning on water colour. Relevant research has taken place at three scales: laboratory experiments on peat cores, plot scale sampling of soil waters and catchment scale sampling of stream waters. While laboratory studies suggest burning increases colour production, the evidence from catchment and plot studies is contradictory. Plot studies suggest colour production may decrease or remain unchanged following burning although there is evidence for some transient changes. Catchment studies suggest prescribed moorland burning causes stream water colour to increase, although in most cases the evidence is not clear cut since most studies could not clearly disentangle the effects of burning from those of vegetation cover. The differences in findings between plot and catchment studies may be explained by: i) the short-term nature of some studies which do not measure long-term response and recovery times to burning; ii) the lack of colour measurements from shallow soil depths which contribute more to streamflow than soil water from deeper in the peat; and iii) the possibility of hydrological interactions occurring between different experimental plots at some sites. Additionally, the increase in recent patch burning in some catchments that has been statistically attributed by some authors to increases in stream water colour cannot be reconciled with theoretical calculations. When dilution with waters derived from other parts of the catchment are taken into account, large values of colour have to be theoretically derived from those recently burnt areas that occupy a small proportion of the catchment area in order to balance the change in stream water colour observed in recent years. Therefore, much further process-based work is required to properly investigate whether prescribed vegetation burning is a direct driver of enhanced colour and DOC in upland streams, rivers and lakes.


Assuntos
Cor , Incêndios , Água Doce , Qualidade da Água , Carbono , Água Subterrânea , Lagos , Rios , Solo
11.
Eur Respir J ; 38(2): 303-9, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21177840

RESUMO

There is growing evidence that asthma symptoms can be aggravated or events triggered by exposure to indoor nitrogen dioxide (NO(2)) emitted from unflued gas heating. The impact of NO(2) on the respiratory health of children with asthma was explored as a secondary analysis of a randomised community trial, involving 409 households during the winter period in 2006 (June to September). Geometric mean indoor NO(2) levels were 11.4 µg · m(-3), while outdoor NO(2) levels were 7.4 µg · m(-3). Higher indoor NO(2) levels (per logged unit increase) were associated with greater daily reports of lower (mean ratio 14, 95% CI 1.12-1.16) and upper respiratory tract symptoms (mean ratio 1.03, 95% CI 1.00-1.05), more frequent cough and wheeze, and more frequent reliever use during the day, but had no effect on preventer use. Higher indoor NO(2) levels (per logged unit increase) were associated with a decrease in morning (-17.25 mL, 95% CI -27.63- -6.68) and evening (-13.21, 95% CI -26.03- -0.38) forced expiratory volume in 1 s readings. Outdoor NO(2) was not associated with respiratory tract symptoms, asthma symptoms, medication use or lung function measurements. These findings indicate that reducing NO(2) exposure indoors is important in improving the respiratory health of children with asthma.


Assuntos
Poluição do Ar em Ambientes Fechados/efeitos adversos , Asma/tratamento farmacológico , Dióxido de Nitrogênio/toxicidade , Infecções Respiratórias/induzido quimicamente , Adolescente , Poluição do Ar em Ambientes Fechados/análise , Asma/fisiopatologia , Criança , Tosse/induzido quimicamente , Feminino , Humanos , Masculino , Dióxido de Nitrogênio/análise , Testes de Função Respiratória , Estações do Ano , Espirro/efeitos dos fármacos
12.
AJNR Am J Neuroradiol ; 42(3): 404-413, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33478944

RESUMO

Skull base osteomyelitis is a relatively rare condition, generally occurring as a complication of advanced otologic or sinus infection in immunocompromised patients. Skull base osteomyelitis is generally divided into 2 broad categories: typical and atypical. Typical skull base osteomyelitis occurs secondary to uncontrolled infection of the temporal bone region, most often from necrotizing external otitis caused by Pseudomonas aeruginosa in a patient with diabetes. Atypical skull base osteomyelitis occurs in the absence of obvious temporal bone infection or external auditory canal infection. It may be secondary to advanced sinusitis or deep face infection or might occur in the absence of a known local source of infection. Atypical skull base osteomyelitis preferentially affects the central skull base and can be caused by bacterial or fungal infections. Clinically, typical skull base osteomyelitis presents with signs and symptoms of otitis externa or other temporal bone infection. Both typical and atypical forms can produce nonspecific symptoms including headache and fever, and progress to cranial neuropathies and meningitis. Early diagnosis can be difficult both clinically and radiologically, and the diagnosis is often delayed. Radiologic evaluation plays a critical role in the diagnosis of skull base osteomyelitis, with CT and MR imaging serving complementary roles. CT best demonstrates cortical and trabecular destruction of bone. MR imaging is best for determining the overall extent of disease and best demonstrates involvement of marrow space and extraosseous soft tissue. Nuclear medicine studies can also be contributory to diagnosis and follow-up. The goal of this article was to review the basic pathophysiology, clinical findings, and key radiologic features of skull base osteomyelitis.


Assuntos
Osteomielite/diagnóstico por imagem , Osteomielite/patologia , Base do Crânio/diagnóstico por imagem , Base do Crânio/patologia , Diagnóstico por Imagem/métodos , Humanos
13.
Sci Total Environ ; 766: 144496, 2021 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-33421775

RESUMO

Afforestation is a significant cause of global peatland degradation. In some regions, afforested bogs are now undergoing clear-felling and restoration, often known as forest-to-bog restoration. We studied differences in water-table depth (WTD) and porewater chemistry between intact, afforested, and restored bogs at a raised bog and blanket bog location. Solute concentrations and principal component analysis suggested that water-table drawdown and higher electrical conductivity (EC) and ammonium (NH4-N) concentrations were associated with afforestation. In contrast, higher dissolved organic carbon (DOC) and phosphate (PO4-P) concentrations were associated with deforestation. Drying-rewetting cycles influenced seasonal variability in solute concentrations, particularly in shallower porewater at the raised bog location. WTD was significantly deeper in the oldest raised bog restoration site (~9 years post-restoration) than the intact bog (mean difference = 6.2 cm). However, WTD in the oldest blanket bog restoration site (~17 years post-restoration), where furrows had been blocked, was comparable to the intact bog (mean difference = 1.2 cm). When averaged for all porewater depths, NH4-N concentrations were significantly higher in the afforested than the intact sites (mean difference = 0.77 mg L-1) whereas significant differences between the oldest restoration sites and the intact sites included higher PO4-P (mean difference = 70 µg L-1) in the raised bog and higher DOC (mean difference = 5.6 mg L-1), EC (mean difference = 19 µS cm-1) and lower SUVA254 (mean difference = 0.13 L mg-1 m-1) in the blanket bog. Results indicate felled waste (brash) may be a significant source of soluble C and PO4-P. Mean porewater PO4-P concentrations were between two and five times higher in furrows and drains in which brash had accumulated compared to other locations in the same sites where brash had not accumulated. Creating and maintaining brash-free buffer zones may therefore minimise freshwater impacts.

14.
Microbiol Resour Announc ; 10(50): e0105021, 2021 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-34913717

RESUMO

Here, we report the genome sequences of three bacterial isolates, Kinneretia sp. strain XES5, Shinella sp. strain XGS7, and Vogesella sp. strain XCS3, which were cultured from skin of adult female laboratory-bred Xenopus laevis.

15.
Ann Oncol ; 21(8): 1718-1722, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20080829

RESUMO

BACKGROUND: We treated melanoma patients with temozolomide (TMZ) in the neoadjuvant setting and collected cryopreserved tumor samples before and after treatment. The primary objective was to determine whether the response proportion was higher than previously reported in widely metastatic patients. A secondary objective was to test the feasibility of obtaining adequate tissue before and after treatment for genetic testing. MATERIALS AND METHODS: Chemotherapy-naive melanoma patients who were candidates for surgical resection were eligible. TMZ was administered orally at 75 mg/m(2)/day for 6 weeks of every 8-week cycle. Cycles were repeated until complete response (CR), progression, or stable disease (SD) for two cycles. RESULTS: Of 19 assessable patients, 2 had CRs and 1 had partial response. Four patients had SD; 12 progressed. Tumor O-6-methylguanine-DNA methyltransferase (MGMT) promoter was unmethylated in all nine patients analyzed including from the two CR patients. Pretreatment tumor microarray results were obtained in 16 of 19 patients. CONCLUSIONS: The response proportion to TMZ in the neoadjuvant setting was 16%, not different than in the metastatic setting. Responses were seen even in tumors with a methylated MGMT promoter. Pretreatment cryopreserved tumor adequate for microarray analysis could be obtained in most, but not all, patients. Post-treatment tumor was unavailable in complete responders.


Assuntos
Antineoplásicos/uso terapêutico , Dacarbazina/análogos & derivados , Melanoma/tratamento farmacológico , Adulto , Idoso , Antineoplásicos/efeitos adversos , Quimioterapia Adjuvante , Metilação de DNA , Metilases de Modificação do DNA/genética , Enzimas Reparadoras do DNA/genética , Dacarbazina/efeitos adversos , Dacarbazina/uso terapêutico , Feminino , Humanos , Masculino , Melanoma/patologia , Melanoma/cirurgia , Pessoa de Meia-Idade , Regiões Promotoras Genéticas , Temozolomida , Proteínas Supressoras de Tumor/genética
16.
J Neurosci Res ; 88(8): 1651-63, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20077429

RESUMO

Campylobacteriosis is a frequent antecedent event in Guillain-Barré syndrome (GBS), inducing high-titer serum antibodies for ganglioside antigens in the peripheral nervous system (PNS). Molecular mimicry between the lipooligosaccharide (LOS) component of Campylobacter jejuni and human peripheral nerve gangliosides is believed to play an important role in the pathogenesis of GBS. Conventional treatment strategies for patients with GBS include plasmapheresis, intravenous immunoglobulin (IVIG), and immunosuppression, which are invasive or relatively ineffective. In this study, we used our animal model of GBS, in which Lewis rats were immunized with GD3-like LOS isolated from C.jejuni. The animals developed anti-GD3 ganglioside antibodies and manifested neuromuscular dysfunction. To develop novel therapeutic strategies, we treated the animals by intraperitoneal administration of an anti-GD3 antiidiotype monoclonal antibody (BEC2) that specifically interacts with the pathogenic antibody. The treated animals had a remarkable reduction of anti-GD3 antibody titers and improvement of motor nerve functions. The results suggest that ganglioside mimics, such as antiidiotype antibodies, may be powerful reagents for therapeutic intervention in GBS by neutralizing specific pathogenic antiganglioside antibodies.


Assuntos
Anticorpos Anti-Idiotípicos/uso terapêutico , Gangliosídeos/imunologia , Neurite Autoimune Experimental/terapia , Potenciais de Ação/efeitos dos fármacos , Potenciais de Ação/fisiologia , Animais , Biotinilação/métodos , Campylobacter jejuni/imunologia , Técnicas de Cocultura/métodos , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Ensaio de Imunoadsorção Enzimática/métodos , Canais de Potássio Éter-A-Go-Go/imunologia , Canais de Potássio Éter-A-Go-Go/metabolismo , Canais de Potássio Éter-A-Go-Go/farmacocinética , Feminino , Adjuvante de Freund/imunologia , Lipopolissacarídeos , Neurônios Motores/patologia , Neurônios Motores/ultraestrutura , Músculo Esquelético/fisiologia , Proteínas do Tecido Nervoso/imunologia , Proteínas do Tecido Nervoso/metabolismo , Proteínas do Tecido Nervoso/farmacocinética , Neurite Autoimune Experimental/induzido quimicamente , Neurite Autoimune Experimental/complicações , Neurite Autoimune Experimental/imunologia , Doenças da Junção Neuromuscular/tratamento farmacológico , Doenças da Junção Neuromuscular/etiologia , Doenças da Junção Neuromuscular/metabolismo , Técnicas de Cultura de Órgãos , Ratos , Teste de Desempenho do Rota-Rod/métodos , Nervo Isquiático/patologia , Nervo Isquiático/ultraestrutura , Medula Espinal/fisiologia , Fatores de Tempo
17.
Clin Radiol ; 65(6): 431-9, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20451009

RESUMO

Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease caused by reactivation of JC virus in immunosuppressed patients. The diagnosis is usually suggested on imaging and confirmed by cerebrospinal fluid polymerase chain reaction (PCR) for JC virus DNA. In this article, we review the imaging manifestations of PML on computed tomography (CT), magnetic resonance imaging (MRI), diffusion-weighted imaging (DWI), diffusion tensor imaging (DTI), MR spectroscopy, single photon-emission computed tomography (SPECT) and positron-emission tomography (PET), and outline the role of imaging in follow-up and prognostication.


Assuntos
Leucoencefalopatia Multifocal Progressiva/diagnóstico , Imagem de Difusão por Ressonância Magnética/métodos , Imagem de Tensor de Difusão/métodos , Humanos , Hospedeiro Imunocomprometido , Espectroscopia de Ressonância Magnética/métodos , Tomografia por Emissão de Pósitrons/métodos , Prognóstico , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Estados Unidos
18.
Intern Med J ; 40(8): 561-5, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19811562

RESUMO

AIMS: It has been suggested that elevated mean red cell volume (MCV) may be a predictor of haematological toxicity in rheumatoid arthritis (RA) patients receiving methotrexate (MTX). We wished to identify whether there was an association between MCV, red cell folate and haematological toxicity in patients on MTX monotherapy for the long-term management of RA. METHODS: Evidence of haematological toxicity was sought by note review of patients recruited in a cross-sectional study of MTX monotherapy in RA. Retrospective data included MCVs from before MTX initiation and after 3 and 6 months of treatment. Data were collected prospectively every 6 months for up to 2 years after enrolment. Any record of cytopenia or the development of haematological malignancy was recorded from commencement of MTX until the present day. Red cell folate concentrations were tested on enrolment to the study. RESULTS: A total of 165 patients was included, 74.5% female, median disease duration 7 years (range 3 months-57 years). The median duration of MTX treatment was 74.9 months (range 10-241 months) giving 1030.2 patient-years of MTX exposure. Twenty-four patients (14.5%) had a MCV > 98 fL on study entry. Evidence of haematological abnormality was found in six patients (3.6%); chronic lymphocytic leukaemia (1), persistent lymphocytosis (1), persistent monocytosis (1) and neutropenia (3). There was no association between red cell folate or MCV and haematological toxicity. CONCLUSION: Neutropenia and pancytopenia are rare side-effects of MTX therapy in this cohort. Elevated MCV or low mean red cell folate does not appear to be associated with haematological malignancy or toxicity in this cohort of patients on long-term MTX therapy.


Assuntos
Antirreumáticos/administração & dosagem , Artrite Reumatoide/tratamento farmacológico , Volume de Eritrócitos/efeitos dos fármacos , Doenças Hematológicas/sangue , Metotrexato/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Antirreumáticos/efeitos adversos , Artrite Reumatoide/sangue , Estudos de Coortes , Estudos Transversais , Volume de Eritrócitos/fisiologia , Feminino , Doenças Hematológicas/induzido quimicamente , Humanos , Masculino , Metotrexato/efeitos adversos , Pessoa de Meia-Idade , Neutropenia/sangue , Neutropenia/induzido quimicamente , Pancitopenia/sangue , Pancitopenia/induzido quimicamente , Estudos Prospectivos , Estudos Retrospectivos , Fatores de Tempo , Adulto Jovem
19.
J Exp Child Psychol ; 105(1-2): 20-37, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-19906386

RESUMO

The reported experiments aimed to investigate whether a person and his or her gaze direction presented in the context of a naturalistic scene cause perception, memory, and attention to be biased in typically developing adolescents and high-functioning adolescents with autism spectrum disorder (ASD). A novel computerized image manipulation program presented a series of photographic scenes, each containing a person. The program enabled participants to laterally maneuver the scenes behind a static window, the borders of which partially occluded the scenes. The gaze direction of the person in the scenes spontaneously cued attention of both groups in the direction of gaze, affecting judgments of preference (Experiment 1a) and causing memory biases (Experiment 1b). Experiment 2 showed that the gaze direction of a person cues visual search accurately to the exact location of gaze in both groups. These findings suggest that biases in preference, memory, and attention are caused by another person's gaze direction when viewed in a complex scene in adolescents with and without ASD.


Assuntos
Atenção , Transtornos Globais do Desenvolvimento Infantil/psicologia , Fixação Ocular , Memória , Percepção Visual , Adolescente , Intermitência na Atenção Visual , Criança , Feminino , Humanos , Masculino , Preconceito , Comportamento Social
20.
Br J Cancer ; 100(1): 167-9, 2009 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-19018256

RESUMO

We analysed data on 8987 larynx and 174060 lung cancer patients diagnosed between 1985 and 2004, of which 17.3% of larynx and 35.5% of lung cancers were in females. The age-standardised rates for each cancer declined in both sexes, but since the 1990s, the rates in females over 70 years of age have been diverging.


Assuntos
Neoplasias Laríngeas/epidemiologia , Neoplasias Pulmonares/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Inglaterra/epidemiologia , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Fatores de Tempo
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