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1.
Nat Commun ; 11(1): 1671, 2020 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-32245968

RESUMO

Charge ordering creates a spontaneous array of differently charged ions and is associated with electronic phenomena such as superconductivity, colossal magnetoresistances (CMR), and multiferroicity. Charge orders are usually suppressed by chemical doping and site selective doping of a charge ordered array has not previously been demonstrated. Here we show that selective oxidation of one out of eight distinct Fe2+ sites occurs within the complex Fe2+/Fe3+ ordered structure of 2%-doped magnetite (Fe3O4), while the rest of the charge and orbitally ordered network remains intact. This 'charge order within a charge order' is attributed to the relative instability of the trimeron distortion surrounding the selected site. Our discovery suggests that similar complex charge ordered arrays could be used to provide surface sites for selective redox reactions, or for storing information by doping specific sites.

2.
Adv Dent Res ; 29(1): 48-54, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29355417

RESUMO

This article aims to outline the early development of a King's College London dental spinout company, Reminova, formed to commercialize a novel clinical method of caries remineralization: electrically accelerated and enhanced remineralization (EAER). This method is being developed to address the unmet clinical need identified by modern caries management strategies to keep enamel "whole" through remineralization of clinical caries as a form of nonoperative caries treatment for initial-stage and moderate lesions. A progressive movement within dentistry is shifting away from the restorative-only model, which, it is suggested, has failed. The high prevalence of initial-stage caries across populations provides a significant opportunity to prevent restorations and reduce repeat restorations over a patient's lifetime. Reminova has set out to provide a method to repair lesions without drilling, filling, pain, or injections. The article outlines the rationale for and the chronological stages of the technology and company development. It then outlines corroborative evidence to show that EAER treatment can, in this preliminary in vitro investigation, remineralize clinically significant caries throughout the depth of the lesion as measured by Knoop microhardness and corroborated by scanning electron microscopy. Furthermore, the presented data show that EAER-treated enamel is harder than the healthy enamel measured nearby in each sample and is very similar in appearance to healthy enamel from the subjective interpretation made possible by scanning electron microscopy imagery. The data presented also show that this more "complete" remineralization to a high hardness level has been achieved with 2 remineralizing agents via in vitro human tooth samples. The broad clinical potential of this new treatment methodology seems to be very encouraging from these results. Reminova will strive to continue its mission, to ensure that, in the future, dental teams will not need to drill holes for the treatment of initial-stage and moderate caries lesions.


Assuntos
Cárie Dentária/prevenção & controle , Esmalte Dentário/química , Iontoforese/métodos , Desmineralização do Dente/terapia , Difusão de Inovações , Dureza , Humanos , Propriedades de Superfície , Remineralização Dentária/métodos , Reino Unido
3.
Proc Math Phys Eng Sci ; 473(2207): 20170491, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29225500

RESUMO

This work discusses an experimental technique for studying the mechanics of three-dimensional (3D) granular solids. The approach combines 3D X-ray diffraction and X-ray computed tomography to measure grain-resolved strains, kinematics and contact fabric in the bulk of a granular solid, from which continuum strains, grain stresses, interparticle forces and coarse-grained elasto-plastic moduli can be determined. We demonstrate the experimental approach and analysis of selected results on a sample of 1099 stiff, frictional grains undergoing multiple uniaxial compression cycles. We investigate the inter-particle force network, elasto-plastic moduli and associated length scales, reversibility of mechanical responses during cyclic loading, the statistics of microscopic responses and microstructure-property relationships. This work serves to highlight both the fundamental insight into granular mechanics that is furnished by combined X-ray measurements and describes future directions in the field of granular materials that can be pursued with such approaches.

4.
Chem Commun (Camb) ; 52(27): 4864-7, 2016 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-26908195

RESUMO

A remarkably complex electronic order of Fe(2+)/Fe(3+) charges, Fe(2+) orbital states, and weakly metal-metal bonded Fe3 units known as trimerons, was recently discovered in stoichiometric magnetite (Fe3O4) below the 125 K Verwey transition. Here, the low temperature crystal structure of a natural magnetite from a mineral sample has been determined using the same microcrystal synchrotron X-ray diffraction method. Structure refinement demonstrates that the natural sample has the same complex electronic order as pure synthetic magnetite, with only minor reductions of orbital and trimeron distortions. Chemical analysis shows that the natural sample contains dopants such as Al, Si, Mg and Mn at comparable concentrations to extraterrestrial magnetites, for example, as reported in the Tagish Lake meteorite. Much extraterrestrial magnetite exists at temperatures below the Verwey transition and hence our study demonstrates that the low temperature phase of magnetite represents the most complex long-range electronic order known to occur naturally.


Assuntos
Óxido Ferroso-Férrico/química , Conformação Molecular
5.
Ann Surg Oncol ; 16(4): 1043-50, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19165543

RESUMO

BACKGROUND: The relationship between obesity and cancer has become of particular interest due to the rapidly growing prevalence of overweight individuals. Obesity predisposes individuals to the development of hepatic steatosis and is an independent risk factor for several neoplasms. Toll-like receptor 4 (TLR4) is the innate receptor for endotoxin, and steatotic livers are known to be sensitive to endotoxin. TLR4 signaling has been shown to have proneoplastic effects in vitro due to its effect on immune surveillance. Thus far, studies have predominantly focused on the effect of tumor-cell-derived TLR4 without regard to host TLR4 signaling. RESULTS: In the present study we show that steatotic livers have increased expression of TLR4. Obese animals developed higher metastatic tumor burden in the liver than lean controls regardless of the presence or absence of intact host TLR4. After silencing TLR4 expression using RNAi in the mouse colon cancer cell line MC38, there was a significant decrease in metastatic tumor burden within the liver of obese animals. CONCLUSIONS: These findings demonstrate that steatotic livers have increased susceptibility to metastatic tumor growth and that silencing tumor cell TLR4 reduces metastatic tumor burden in steatotic liver.


Assuntos
Neoplasias Colorretais/genética , Fígado Gorduroso/metabolismo , Inativação Gênica , Neoplasias Hepáticas/genética , Receptor 4 Toll-Like/genética , Carga Tumoral/genética , Animais , Linhagem Celular Tumoral , Neoplasias Colorretais/secundário , Modelos Animais de Doenças , Fígado Gorduroso/etiologia , Fígado Gorduroso/genética , Predisposição Genética para Doença , Neoplasias Hepáticas/secundário , Masculino , Camundongos , Obesidade/complicações , Obesidade/genética , Obesidade/imunologia , Receptor 4 Toll-Like/biossíntese
6.
Acta Crystallogr A ; 64(Pt 1): 169-80, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18156682

RESUMO

Following the seminal work of Von Dreele, powder X-ray diffraction studies on proteins are being established as a valuable complementary technique to single-crystal measurements. A wide range of small proteins have been found to give synchrotron powder diffraction profiles where the peak widths are essentially limited only by the instrumental resolution. The rich information contained in these profiles, combined with developments in data analysis, has stimulated research and development to apply the powder technique to microcrystalline protein samples. In the present work, progress in using powder diffraction for macromolecular crystallography is reported.


Assuntos
Cristalografia por Raios X/métodos , Difração de Pó/métodos , Proteínas/química , Animais , Galinhas , Clara de Ovo/química , Insulina/química , Metamioglobina/química , Modelos Moleculares , Muramidase/química , Membrana Purpúrea/química
7.
J Nanosci Nanotechnol ; 8(11): 5896-902, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19198323

RESUMO

By combining nanosphere lithography (NSL) with metal evaporation at two different chamber pressures, ternary metallic nanostructures with 3D topography were fabricated and characterized by field emission gun scanning electron microscopy (FEG-SEM) and atomic force microscopy (AFM). The nanostructures consist of 340 nm silicon patches surrounded by a chromium mesh of varying height and gold triangular pillars with a height of 40 nm and a diameter of about 200 nm. While NSL was applied due to its ease of use, evaporation at different chamber pressures can be combined with any kind of template mask comprising convex shape to yield novel kinds of ternary nanostructures analogous to the ones presented here. The method shows to be more versatile than plasma-based deposition techniques due to avoidance of substrate charging effects and a freely adjustable chamber pressure.


Assuntos
Cristalização/métodos , Ouro/química , Nanoestruturas/química , Nanoestruturas/ultraestrutura , Nanotecnologia/métodos , Gases/química , Substâncias Macromoleculares/química , Teste de Materiais , Conformação Molecular , Tamanho da Partícula , Propriedades de Superfície
8.
Mikrobiol Z ; 68(4): 10-20, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-17100323

RESUMO

Two orange-pigmented Gram-positive, aerobic bacteria were isolated from enrichment culture during degradation of brown alga Fucus evanescens thalluses. In this work, atomic force microscopy (AFM) has been used to study the cell morphology. The non-contact mode imaging revealed unusual irregular coccoid shape of cells, possessing a single flagellum. Bacteria produced carotenoid pigments, were chemo-organotrophic, alkaliphilic and halo-tolerant growing well on nutrient media containing up to 15% NaCl. Growth temperature ranged from 5 to 45 degrees C. The DNA base compositions were 48 mol% G + C and the level of DNA similarity of two strains was conspecific (98%). A comparative phylogenetic analysis of 16S rRNA gene sequences revealed that the strain KMM 3738 tightly clustered with recently described Planococcus maritimus (99.9% 16S rRNA gene sequence similarity). DNA-DNA hybridisation experiments revealed that DNA from the KMM 3738 showed 12-15% and 16-35% of genetic relatedness with the DNA of type strains of the genera Planomicrobium and Planococcus, respectively, and 87% with DNA from Planococcus maritimus, indicating that new isolates belong to the later species.


Assuntos
Fucus/microbiologia , Bactérias Gram-Positivas/isolamento & purificação , Técnicas de Tipagem Bacteriana , DNA Bacteriano/análise , Bactérias Gram-Positivas/genética , Bactérias Gram-Positivas/ultraestrutura , Microscopia Eletrônica de Transmissão , Filogenia , RNA Bacteriano/análise , RNA Ribossômico 16S/análise
9.
Diabet Med ; 21(1): 32-8, 2004 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-14706051

RESUMO

AIMS: The aim of this study was to evaluate an innovative approach to the provision of primary care-based diabetes services in Bradford, UK. The service model differs from others in comprising 19 clinics which offer a specialist service, intermediate between primary and secondary care, to all patients within the Bradford area. METHODS: The study included: analysis of referral, attendance and register data; questionnaires to general practitioners (GPs) and specialist clinic providers; qualitative interviews with clinic and other professional staff and patients; and an economic analysis. RESULTS: The 19 clinics adopt a range of organizational models. In the first 3 1/2 years, 2415 patients were referred. There was a significant reduction in out-patient attendances at hospital, but also a significant increase in overall patient attendances. Specialist clinic patients differed from hospital patients in being older and having had diabetes for longer since diagnosis. Ten of the 14 clinics run by practising GPs attracted more referrals from within their practices than from outside. GPs and patients across the city believed the clinics were valuable, the main benefits being geographical accessibility, availability of specialists in a community setting, short waiting times for first appointments at most clinics, and continuity of staff. Their reservations included a lack of strategic planning in the location of clinics, long waiting times at some clinics, and poor communication at some clinics with referring GPs. The cost of the primary care clinics is similar to hospital clinics. CONCLUSIONS: This model of specialist primary care services offers an opportunity to develop diabetes services that are convenient to patients, popular with practitioners, and increase capacity. However, the shortcomings as well as the advantages of the model need to be addressed if it is to be implemented elsewhere or for other patient groups.


Assuntos
Atenção à Saúde/organização & administração , Diabetes Mellitus/terapia , Atenção Primária à Saúde/organização & administração , Adulto , Idoso , Instituições de Assistência Ambulatorial/organização & administração , Atitude do Pessoal de Saúde , Atitude Frente a Saúde , Custos e Análise de Custo , Atenção à Saúde/economia , Inglaterra , Medicina de Família e Comunidade/economia , Medicina de Família e Comunidade/organização & administração , Humanos , Pessoa de Meia-Idade , Inovação Organizacional , Aceitação pelo Paciente de Cuidados de Saúde , Médicos de Família/psicologia , Atenção Primária à Saúde/economia , Encaminhamento e Consulta , Sistema de Registros
10.
Cochrane Database Syst Rev ; (1): CD002158, 2002.
Artigo em Inglês | MEDLINE | ID: mdl-11869625

RESUMO

BACKGROUND: A number of different inhaler devices are available to deliver beta2-agonist bronchodilators in asthma. These include hydrofluoroalkane (HFA) or chlorofluorocarbon (CFC)-free propelled pressurised metered dose inhalers (pMDIs) and dry powder devices. OBJECTIVES: To determine the clinical effectiveness of pMDI compared with any other available handheld inhaler device for the delivery of short-acting beta-2 agonist bronchodilators in non-acute asthma in children and adults. SEARCH STRATEGY: The Cochrane Collaboration Clinical Trials register was searched for studies as well as separate additional searches carried out on MEDLINE, EMBASE, CINAHL and also on the Current Contents Index as well as the Science Citation Index. In addition, 17 individual online respiratory journals and 12 electronically available clinical trial databases were also searched. The UK pharmaceutical companies who manufacture inhaled asthma medication were contacted in order to obtain details of any published or unpublished studies. SELECTION CRITERIA: - The full texts of all potentially relevant articles were reviewed independently by two reviewers. DATA COLLECTION AND ANALYSIS: Fixed and random effect models were used. Dichotomous outcomes were assessed using Odds Ratios or Relative Risks (RR) with 95% Confidence Intervals (95%CI). MAIN RESULTS: Eighty-four randomised controlled trials were included in this review, but few could be combined to assess a specific outcome for a given delivery device comparison. Only two studies required demonstration of adequate pMDI technique as an entry requirement. There were no difference between a standard CFC containing pMDI and any other device for most outcomes. Regular use of HFA-pMDI containing salbutamol reduced the requirement for short courses of oral corticosteroids (3 trials, 519 patients: RR 0.67; 95% CI 0.49, 0.91); however the total number of exacerbations were unchanged (3 trials, 1271 patients: RR 1.0; 95% CI 0.75, 1.33). REVIEWER'S CONCLUSIONS: In patients with stable asthma, short-acting beta-2 bronchodilators in standard CFC-pMDI's are as effective as any other devices. The effect of HFA-pMDI on requirement for oral corticosteroid courses to treat acute exacerbations should be confirmed. Effectiveness studies that use an intention-to-treat analysis are required.


Assuntos
Agonistas Adrenérgicos beta/administração & dosagem , Asma/tratamento farmacológico , Broncodilatadores/administração & dosagem , Nebulizadores e Vaporizadores , Adulto , Criança , Humanos , Pressão , Ensaios Clínicos Controlados Aleatórios como Assunto
11.
Aliment Pharmacol Ther ; 15(9): 1323-9, 2001 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-11552902

RESUMO

BACKGROUND: Thromboxanes are produced in excess and platelets are activated in active Crohn's disease. Preliminary reports have suggested that ridogrel, a dual thromboxane synthase inhibitor and receptor antagonist, may have therapeutic benefit in patients with inflammatory bowel disease. AIMS: To investigate the efficacy of ridogrel in patients with active Crohn's disease. PATIENTS AND METHODS: This was an international, multicentre, randomized, double-blind, placebo-controlled trial of 5 mg/day oral ridogrel for 12 weeks in 85 patients with moderately active Crohn's disease. Sixty patients were randomized to receive ridogrel, and 25 to placebo. The Crohn's disease activity index (CDAI) was used to assess disease activity: remission was defined as a CDAI < 150. Changes in clinical condition, as assessed by the Harvey-Bradshaw index, global evaluation by the investigator and the patient, and blood measures of inflammation, were used as secondary outcomes. RESULTS: The patients' mean (s.d.) CDAI at recruitment was 277 (68) in the ridogrel treated group and 265 (70) in the placebo group. At their final assessment, 20 out of 60 (35%) patients who had been given ridogrel in an intention-to-treat analysis and seven out of 25 (28%) patients given placebo were in remission (no significant difference). No significant differences in Harvey- Bradshaw index or global evaluation were noted between patients given ridogrel and those given placebo. Adverse events were similar in both groups. CONCLUSION: A 5-mg dose of oral ridogrel was not more effective than placebo in inducing remission in patients with moderately active Crohn's disease. If thromboxane synthesis and platelet function are to be targeted for the treatment of Crohn's disease, more potent agents require development and assessment.


Assuntos
Doença de Crohn/tratamento farmacológico , Ácidos Pentanoicos/uso terapêutico , Piridinas/uso terapêutico , Tromboxano-A Sintase/antagonistas & inibidores , Adulto , Método Duplo-Cego , Feminino , Humanos , Masculino , Pacientes Desistentes do Tratamento , Falha de Tratamento
12.
Pathology ; 33(1): 50-2, 2001 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11280609

RESUMO

We report the case of an elderly woman excreting high levels (about 5 x 10(5) virions per gram of faeces) of Norwalk-like virus (NLV) in the absence of any clinical symptoms of gastroenteritis. Analysis by reverse transcription, polymerase chain reaction and DNA sequencing was carried out on a 342-nucleotide region of open reading frame 1. This indicated that the NLV belonged to genogroup 2 and was more closely related to the Camberwell subgroup, the most common circulating in southeast Australia at present, than to the Norwalk and Mexico viruses.


Assuntos
Infecções por Caliciviridae/virologia , Fezes/virologia , Gastroenterite/virologia , Vírus Norwalk/isolamento & purificação , Eliminação de Partículas Virais , Idoso , Primers do DNA/química , DNA Viral/análise , Feminino , Humanos , Dados de Sequência Molecular , Vírus Norwalk/classificação , Vírus Norwalk/fisiologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Análise de Sequência de DNA
13.
Phys Rev Lett ; 87(26): 266401, 2001 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-11800847

RESUMO

The crystal structure of Fe(3)O(4) below the 122 K Verwey transition has been refined using high-resolution x-ray and neutron powder diffraction data. The refinements give direct evidence for charge ordering (CO) over four independent octahedral Fe sites, two with a charge of +2.4 and the other two of +2.6. CO schemes consistent with our model do not meet the widely accepted Anderson condition of minimum electrostatic repulsion. Instead we propose that CO is driven primarily by a [001] electronic instability, which opens a gap at the transition through a charge density wave mechanism.

14.
Dig Dis Sci ; 44(9): 1899-901, 1999 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-10505732

RESUMO

In order to investigate the role of sucralfate in active ulcerative colitis, 60 patients were randomized to receive either sucralfate enemas (20 g/100 ml) or methylprednisolone enemas (20 mg/100 ml). The enemas were administered twice daily for one week, and then once daily for three weeks. Clinical evaluation was documented at entry and at two weeks and four weeks. The sigmoidoscopic appearance of the rectal mucosa was scored, and rectal biopsies taken at entry and at four weeks. Results indicated similar reduction in diarrhea and rectal bleeding at two weeks and at four weeks. Sigmoidoscopy demonstrated similar significant improvement in the macroscopic appearance of the rectal mucosa in both groups (8.28 to 6.20 in sucralfate group, P < 0.02; and 8.72 to 6.36 in the methylprednisolone treated group, P < 0.04). Histologic assessment, likewise, showed similar improvements in the two groups. This study indicates that sucralfate enemas may be useful in the treatment of ulcerative proctosigmoiditis.


Assuntos
Anti-Inflamatórios/administração & dosagem , Antiulcerosos/administração & dosagem , Colite Ulcerativa/tratamento farmacológico , Metilprednisolona/efeitos adversos , Sucralfato/administração & dosagem , Administração Tópica , Adulto , Anti-Inflamatórios/uso terapêutico , Antiulcerosos/uso terapêutico , Colite Ulcerativa/patologia , Enema , Feminino , Glucocorticoides , Humanos , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/patologia , Masculino , Metilprednisolona/uso terapêutico , Pessoa de Meia-Idade , Estudos Prospectivos , Reto/efeitos dos fármacos , Reto/patologia , Método Simples-Cego , Sucralfato/uso terapêutico
15.
N Engl J Med ; 339(6): 370-4, 1998 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-9691103

RESUMO

BACKGROUND: Crohn's disease is often treated with glucocorticoids or mesalamine. We compared the efficacy and safety of controlled-ileal-release budesonide capsules and slow-release mesalamine tablets in patients with active Crohn's disease affecting the ileum, the ascending colon, or both. METHODS: In a double-blind, multicenter trial, we enrolled 182 patients with scores of 200 to 400 on the Crohn's Disease Activity Index (with higher scores indicating greater disease activity) and randomly assigned 93 to receive 9 mg of budesonide once daily and 89 to receive 2 g of mesalamine twice daily for 16 weeks. The primary efficacy variable was clinical remission, defined as a score of 150 or less on the Crohn's Disease Activity Index. RESULTS: In the analysis of all patients who received at least one dose of study drug, the rates of remission after 8 weeks of treatment were 69 percent in the budesonide group and 45 percent in the mesalamine group (P=0.001); the respective rates after 16 weeks of treatment were 62 percent and 36 percent (P<0.001). Seventy-seven patients in the budesonide group completed the 16 weeks of treatment, as compared with 50 patients in the mesalamine group (P<0.001). The numbers of patients with adverse events were similar in the two groups, but those assigned to budesonide had fewer severe adverse events. Among patients who completed 16 weeks of treatment, the morning plasma cortisol value was normal in 67 percent of budesonide-treated patients and 83 percent of mesalamine-treated patients (P=0.06); 90 percent and 100 percent, respectively, had normal increases in cortisol in response to cosyntropin (P=0.02). CONCLUSIONS: In patients with active Crohn's disease affecting the ileum, the ascending colon, or both, a controlled-ileal-release formulation of budesonide was more effective in inducing remission than a slow-release formulation of mesalamine.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Budesonida/uso terapêutico , Doença de Crohn/tratamento farmacológico , Mesalamina/uso terapêutico , Administração Tópica , Adolescente , Adulto , Idoso , Anti-Inflamatórios/efeitos adversos , Anti-Inflamatórios não Esteroides/efeitos adversos , Budesonida/efeitos adversos , Preparações de Ação Retardada , Método Duplo-Cego , Feminino , Humanos , Hidrocortisona/sangue , Masculino , Mesalamina/efeitos adversos , Pessoa de Meia-Idade , Indução de Remissão
16.
J Accid Emerg Med ; 14(3): 134-8, 1997 May.
Artigo em Inglês | MEDLINE | ID: mdl-9193972

RESUMO

OBJECTIVE: The rate of rise of total plasma creatine kinase (CK) activity in the first 12 hours from presentation can be used to diagnose acute myocardial infarction. The aim of this study was to evaluate the performance of an abbreviated form of this test in the diagnosis of acute myocardial infarction in patients in whom the initial electrocardiogram was inconclusive. METHODS: Using a protocol that requires only two CK measurements (separated by four hours) to estimate the rate of rise, the performance of the test was investigated using data accrued from 345 consecutive admissions with suspected acute myocardial infarction. RESULTS: A CK increment (delta CK) of > 20% in the first four hours from presentation had a diagnostic sensitivity of 84.4% (95% confidence interval 75.5 to 93.3), specificity of 85.8% (80.1 to 91.5), positive predictive accuracy of 73.0% (62.9 to 83.1), and negative predictive accuracy of 92.4% (87.9 to 96.9). Using more stringent diagnostic criteria (delta CK > 20% and 4 h CK value > 160 U/litre) resulted in an increase in specificity and positive predictive accuracy to 96.5% and 91.1% respectively, and a small reduction in sensitivity and negative predictive accuracy to 79.7% and 91.3%, respectively, 94% of all infarcts were correctly identified using the ECG as the initial investigation and paired CK measurement as an additional test when this was inconclusive. In the 44 patients who received thrombolysis on the basis of an early biochemical diagnosis of acute myocardial infarction, the median time delay (75th centile) to thrombolysis was 10.75 (SD 15.0) hours. CONCLUSIONS: When the presenting ECG is non-diagnostic, sequential sampling of cardiac enzymes is a feasible alternative in the early diagnosis of patients with suspected myocardial infarction, even in the emergency setting. Further studies are required to define the optimal biochemical assay and timed sampling protocol.


Assuntos
Creatina Quinase/sangue , Eletrocardiografia , Infarto do Miocárdio/diagnóstico , Idoso , Aspartato Aminotransferases/sangue , Intervalos de Confiança , Emergências , Estudos de Avaliação como Assunto , Estudos de Viabilidade , Feminino , Humanos , L-Lactato Desidrogenase/sangue , Masculino , Infarto do Miocárdio/sangue , Infarto do Miocárdio/tratamento farmacológico , Valor Preditivo dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade , Terapia Trombolítica , Fatores de Tempo
17.
J Virol ; 71(2): 1362-9, 1997 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-8995660

RESUMO

Reoviruses isolated from persistently infected cultures (PI viruses) can grow in the presence of ammonium chloride, a weak base that blocks acid-dependent proteolysis of viral outer-capsid proteins during viral entry into cells. We used reassortant viruses isolated from crosses of wild-type (wt) reovirus strain, type 1 Lang, and three independent PI viruses, L/C, PI 2A1, and PI 3-1, to identify viral genes that segregate with the capacity of PI viruses to grow in cells treated with ammonium chloride. Growth of reassortant viruses in ammonium chloride-treated cells segregated with the S1 gene of L/C and the S4 gene of PI 2A1 and PI 3-1. The S1 gene encodes viral attachment protein sigma1, and the S4 gene encodes outer-capsid protein sigma3. To identify mutations in sigma3 selected during persistent reovirus infection, we determined the S4 gene nucleotide sequences of L/C, PI 2A1, PI 3-1, and four additional PI viruses. The deduced amino acid sequences of sigma3 protein of six of these PI viruses contained a tyrosine-to-histidine substitution at residue 354. To determine whether mutations selected during persistent infection alter cleavage of the viral outer capsid, the fate of viral structural proteins was assessed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis after treatment of virions of wt and PI viruses with chymotrypsin in vitro. Proteolysis of PI virus outer-capsid proteins sigma3 and mu1C occurred with faster kinetics than proteolysis of wt virus outer-capsid proteins. These results demonstrate that mutations in either the S1 or S4 gene alter acid-dependent disassembly of the reovirus outer capsid and suggest that increased efficiency of proteolysis of viral outer-capsid proteins is important for maintenance of persistent reovirus infections of cultured cells.


Assuntos
Capsídeo/genética , Genes Virais , Células L/virologia , Vírus Reordenados/genética , Infecções por Reoviridae/virologia , Reoviridae/fisiologia , Montagem de Vírus/genética , Animais , Regulação Viral da Expressão Gênica , Camundongos , Mutação
18.
Aliment Pharmacol Ther ; 9(6): 673-83, 1995 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-8824656

RESUMO

UNLABELLED: INVESTIGATORS: This multicentre study was conducted by 29 principal investigators in 11 countries. AIMS: To compare the safety and efficacy of oral mesalazine (Mesasal/Claversal, 5-ASA) 1.5 g b.d. in comparison with placebo in the maintenance of remission in 286 patients with Crohn's disease. MATERIALS AND METHODS: Patients had to score less than 150 in their Crohn's Disease Activity Index (CDAI), and had to have had one period of clinical activity (CDAI > 150) within 18 months of the study start. Patients were randomized to receive 5-ASA 1.5 g b.d. daily or matching placebo for 12 months. Study visits were scheduled for months 1, 3, 6, 9 and 12, or when symptoms suggested a relapse of the disease. Relapse was defined as a CDAI score greater than 150, with at least a 60-point increase from the baseline index score. None of the patients used glucocorticoids or immunosuppressants during the trial. RESULTS: In the first group, 207 patients with Crohn's colitis or ileocolitis were randomized: there were 101 females and 106 males, in age range 18-71 years. A total of 106 patients (51 in the 5-ASA group and 55 in the placebo group) were withdrawn from the study due to adverse events, insufficient therapeutic effect, or for other reasons. This left 101 patients (51 in the 5-ASA group and 50 in the placebo group) who completed the 12-month trial. In the second group, 79 patients with Crohn's ileitis were randomized to treatment. There were 53 females and 26 males, age range 18-66 years. A total of 41 patients (19 in the 5-ASA group and 22 in the placebo group) were withdrawn from the study. This left 38 patients (17 in the 5-ASA group and 21 in the placebo group) who completed the 12-month trial. The primary efficacy variable was the CDAI. A protocol-eligible analysis and an intent-to-treat analysis were performed. No statistical differences were noted between the two analyses. In patients with Crohn's colitis or ileocolitis, or in those with ileitis, no statistically significant differences were noted with respect to the relapse rates between the 5-ASA and the placebo treatment groups. Adverse events in the gastrointestinal system were the most frequently reported in both treatment groups. Many of the events such as diarrhoea or abdominal pain are symptoms of Crohn's disease. The majority of the events reported were mild or moderate in severity. In neither study was the prevalence of adverse events or the proportion of drop-outs different between patients in the treatment or in the placebo groups. The site of the Crohn's disease had no effect on the frequency of adverse events. CONCLUSION: The relapse rates of Crohn's disease were similar for up to 12 months in both the 5-ASA 1.5 g b.d. and the placebo treatment groups.


Assuntos
Ácidos Aminossalicílicos/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Doença de Crohn/tratamento farmacológico , Adulto , Idoso , Ácidos Aminossalicílicos/efeitos adversos , Canadá , Colite/tratamento farmacológico , Método Duplo-Cego , Europa (Continente) , Feminino , Humanos , Ileíte/tratamento farmacológico , Masculino , Mesalamina , Pessoa de Meia-Idade , África do Sul
19.
S Afr Med J ; 85(11): 1176-9, 1995 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-8597010

RESUMO

Debate exists about the role of diet in both the aetiology and the management of ulcerative colitis. To examine the latter, a group of patients with documented ulcerative colitis was studied at the Groote Schuur Hospital Gastro-intestinal Clinic. A total of 18 subjects, 9 female and 9 male, were randomised into active or control groups and followed up weekly for 6 weeks. Subjects in the control group were asked to document but not alter their intake of food and drink. Those in the experimental group had their diets systematically manipulated to exclude foods that appeared to provoke symptoms. The symptoms, sigmoidoscopy and biopsy findings of all subjects were compared before and after. 'Remission' was defined as the passage of normal stools with absence of rectal bleeding. 'Improvement' was defined as a decrease in the number of diarrhoeal stools and/or a diminution of rectal bleeding. At the end of the trial the diet group displayed significantly fewer symptoms than did the controls (P = 0.009; Fisher's exact test). Sigmoidoscopic findings improved in 8 subjects in the diet group compared with 2 of the controls. Histological findings improved in 3 of the diet group as well as in 3 of the controls. There were no foods that provoked symptoms in all patients, though spiced and curried foods and fruits, especially grapes, melon and the citruses, commonly caused diarrhoea. In only 2 patients were symptoms reproduced consistently on reintroduction of a particular food, pork in 1 case and yellow cheese in another.


Assuntos
Colite Ulcerativa/dietoterapia , Adulto , Colite Ulcerativa/complicações , Colite Ulcerativa/patologia , Diarreia/prevenção & controle , Feminino , Hemorragia Gastrointestinal/prevenção & controle , Humanos , Masculino , Indução de Remissão , Sigmoidoscopia , África do Sul
20.
Surg Endosc ; 9(3): 329-31, 1995 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-7597608

RESUMO

An osmotic laxative containing polyethylene glycol and sodium sulfate (Golytely Braintree Laboratories, Inc., Braintree, MA) is widely used to clean the colon for colonoscopy. However, its salty taste makes the mixture unpalatable. We therefore tested the claim that a similar solution but without sodium sulfate (Golytely-RSS Braintree Laboratories, Inc., Braintree, MA) makes preparation of the colon more acceptable to patients in a double-blinded randomized controlled trial. Colonic preparation using polyethylene glycol with or without sodium sulfate was randomized in 100 patients due to undergo colonoscopy. The overall acceptability of the regimen was measured on a linear analogue scale and an estimate of symptoms was obtained. Body weight and serum electrolytes, urea, creatinine, hemoglobin and hematocrit were determined before and after preparation in order to assess fluid absorption. The efficacy of colonic cleansing was graded by the colonoscopist. Four patients did not complete the protocol, 47 received the regimen containing sodium sulfate and 49 received the regimen without it. The two groups did not differ in age or body mass. There was no statistical difference in the overall acceptability of the two regimens to the patients (median acceptability rating 74 for regimen with sodium sulfate, range 4-100 compared with 77 for regimen without, range 3-100, p = 0.32, Mann-Whitney test). Nor was there any difference in taste, nausea, vomiting, cramping or perianal discomfort or in the endoscopists' rating of the cleanliness of the colon. The serum sodium concentration rose slightly (mean 1.6 mmol/L) when the regimen with sodium sulfate was used.(ABSTRACT TRUNCATED AT 250 WORDS)


Assuntos
Catárticos , Colonoscopia , Eletrólitos , Polietilenoglicóis , Sulfatos , Colonoscopia/economia , Custos e Análise de Custo , Método Duplo-Cego , Eletrólitos/química , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Polietilenoglicóis/química , Soluções
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