RESUMO
OBJECTIVES: To prospectively evaluate HiberGene's loop-mediated isothermal amplification (LAMP) assay for detection of group B streptococcus (GBS) in maternal recto-vaginal swabs and compare it with enrichment culture. METHODS: Following ethical approval and informed written consent, two low vaginal and rectal swabs were obtained from 400 pregnant women. One swab was tested for GBS using the rapid LAMP assay (index test), the second swab was tested using enrichment culture (reference standard). Antimicrobial susceptibility testing was performed according to EUCAST guidelines. RESULTS: There were 376 concordant results, 20 discordant and four invalid LAMP results. Among discordant results, six were LAMP negative/culture positive and 14 were LAMP positive/culture negative. The sensitivity was 92.2%, specificity 95.6%, positive predictive value 83.5% and negative predictive value 98.1%. The prevalence of GBS carriage was 19.25% (77/400). Forty-eight of 77 GBS-positive women were colonized vaginally (62.3%) and 70 were colonized rectally (90.9%). Erythromycin resistance was 22.4% (17/76) and clindamycin resistance was 17.1% (13/76). CONCLUSIONS: The LAMP assay is a rapid and simple test with results available in approximately 1 h compared with 48 h for culture. The test has good sensitivity and specificity compared with enrichment culture. This test can be used for rapid antenatal GBS screening.
Assuntos
Técnicas de Amplificação de Ácido Nucleico/métodos , Reto/microbiologia , Infecções Estreptocócicas/diagnóstico por imagem , Streptococcus/genética , Vagina/microbiologia , Feminino , Humanos , Gravidez , Complicações Infecciosas na Gravidez/diagnóstico , Complicações Infecciosas na Gravidez/microbiologia , Prevalência , Estudos Prospectivos , Sensibilidade e Especificidade , Manejo de Espécimes/métodos , Infecções Estreptocócicas/microbiologiaRESUMO
PURPOSE: To report the prevalence of gonococcal conjunctivitis (GC) presenting to a tertiary referral maternity hospital (NMH) and a tertiary referral ophthalmic hospital (RVEEH) from 2011 to 2013 and describe the demographics, clinical presentation, and antibiotic susceptibility of Neisseria gonorrhoeae ocular infections. METHODS: Demographic, clinical, and microbiological data were collected from patients with laboratory confirmed GC. RESULTS: There were 27 556 live births at NMH during the study period, and no case of neonatal GC was identified. Fourteen cases of GC were identified at RVEEH in this period, representing a prevalence of 0.19 cases per 1000 eye emergency attendees. Antibiotic susceptibility data were available on nine cases, of which, all were ceftriaxone- and ciprofloxacin sensitive. 64.3% of patients were male, with a mean age of 18 years. The mean duration of symptoms was 3 days. All patients presented with unilateral conjunctival injection and purulent discharge. Eight cases had visual impairment at presentation and their mean visual acuity was 6/15. Corneal involvement was present in 25% of patients. Uveitis was not detected. On receipt of positive culture and/or PCR results, treatment was altered in two thirds of patients. All patients were referred for full STI screening and all patients showed a full clinical recovery 1 week posttreatment. CONCLUSION: We observed that GC presented in young adults with a male predominance and was rare in neonates. In cases of unilateral purulent conjunctivitis, there should be a high clinical suspicion of GC, early swab for PCR and culture, and knowledge of current CDC-recommended antibiotic guidelines.
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Conjuntivite Bacteriana/epidemiologia , Infecções Oculares Bacterianas/epidemiologia , Gonorreia/epidemiologia , Neisseria gonorrhoeae/isolamento & purificação , Oftalmia Neonatal/diagnóstico , Oftalmia Neonatal/epidemiologia , Adolescente , Antibacterianos/uso terapêutico , Ceftriaxona/uso terapêutico , Criança , Pré-Escolar , Ciprofloxacina/uso terapêutico , Conjuntivite Bacteriana/diagnóstico , Conjuntivite Bacteriana/tratamento farmacológico , Infecções Oculares Bacterianas/diagnóstico , Infecções Oculares Bacterianas/tratamento farmacológico , Feminino , Gonorreia/diagnóstico , Gonorreia/tratamento farmacológico , Maternidades/estatística & dados numéricos , Hospitais Especializados/estatística & dados numéricos , Humanos , Irlanda/epidemiologia , Masculino , Testes de Sensibilidade Microbiana , Neisseria gonorrhoeae/efeitos dos fármacos , Oftalmia Neonatal/tratamento farmacológico , Oftalmologia/estatística & dados numéricos , Reação em Cadeia da Polimerase , Prevalência , Adulto JovemRESUMO
Exercise preconditioning induces neuroprotection after stroke. We investigated the beneficial role of heat shock protein-70 (HSP-70) and phosphorylated extracellular-signal-regulated-kinase 1/2 (pERK 1/2), as they pertain to reducing apoptosis and their influence on Bcl-x(L), Bax, and apoptosis-inducing factor (AIF) in rats subjected to ischemia and reperfusion. Adult male Sprague-Dawley rats were subjected to 30 min of exercise on a treadmill for 1, 2, or 3 weeks. Stroke was induced by a 2-h middle cerebral artery (MCA) occlusion using an intraluminal filament. Protein levels of HSP-70, pERK 1/2, Bcl-x(L), Bax, and AIF were analyzed using Western blot. Neuroprotection was based on levels of apoptosis (TUNEL) and infarct volume (Nissl staining). Immunocytochemistry was used for cellular expression of HSP-70 and pERK 1/2. Significant (P<0.05) up-regulation of HSP-70 and pERK 1/2 after 3 weeks of exercise coincided with significant (P<0.05) reduction in neuronal apoptosis and brain infarct volume. Inhibition of either one of these two factors showed a significant (P<0.05) reversal in the neuroprotection. Bax and AIF were down-regulated, while levels of Bcl-x(L) were up-regulated in response to stroke after exercise. Inhibiting HSP-70 or pERK 1/2 reversed this resultant increase or decrease. Our results indicate that exercise diminishes neuronal injury in stroke by up-regulating HSP-70 and ERK 1/2.
Assuntos
Apoptose/fisiologia , Proteínas de Choque Térmico HSP70/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Degeneração Neural/terapia , Condicionamento Físico Animal/fisiologia , Acidente Vascular Cerebral/terapia , Animais , Proteínas Reguladoras de Apoptose/metabolismo , Infarto Encefálico/fisiopatologia , Infarto Encefálico/prevenção & controle , Infarto Encefálico/terapia , Citoproteção/fisiologia , Modelos Animais de Doenças , Terapia por Exercício/métodos , Imuno-Histoquímica , Infarto da Artéria Cerebral Média/metabolismo , Infarto da Artéria Cerebral Média/fisiopatologia , Infarto da Artéria Cerebral Média/terapia , Masculino , Degeneração Neural/fisiopatologia , Degeneração Neural/prevenção & controle , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/fisiopatologia , Traumatismo por Reperfusão/terapia , Acidente Vascular Cerebral/metabolismo , Acidente Vascular Cerebral/fisiopatologia , Regulação para Cima/fisiologiaRESUMO
AIM: Bone-anchored hearing aids are well established, implanted devices. We present two patients who suffered mixed hearing loss and who underwent titanium implant placement in the temporal bone to enable attachment of bone-anchored hearing aids. Osseointegration is necessary for such implants to function. We report these two cases to highlight how such osseointegration may be disrupted. METHOD: Attached tissue from the explanted or removed titanium implants was examined by transmission electron microscopy and histopathological analysis. RESULTS: Attached tissue from both implants showed the presence of keratinocytes at the titanium implant and living bone interface. This was confirmed by histopathological analysis. In one case, there was frank keratinocyte proliferation, which had led to osseointegration failure; in the other case, such proliferation was present but not so advanced. CONCLUSION: These findings suggest that, in the cases reported, keratinocytes implanted between the titanium and the living bone, leading to disruption of osseointegration.
Assuntos
Implante Coclear/efeitos adversos , Implantes Cocleares/efeitos adversos , Perda Auditiva Condutiva-Neurossensorial Mista/cirurgia , Queratinócitos/fisiologia , Osseointegração/fisiologia , Idoso , Implantes Cocleares/microbiologia , Humanos , Masculino , Microscopia Eletrônica , Otite Média Supurativa/microbiologia , Falha de PróteseRESUMO
DefibViz is a software application developed for defibrillation simulation and visualization. It exploits both surface techniques and methods for the interactive exploration of volumetric datasets for the analysis of transthoracic defibrillation simulation results. DefibViz\ has a graphical user interface for the specification of the shape, size, position, and applied voltage of a defibrillator's electrodes. An option is provided for using 3-D slice plane widgets, which operate on the volumetric datasets, such that the distribution of the voltage gradient induced by an electric shock can be visually inspected in various tissues throughout the myocardium and torso. One goal of DefibViz is to enhance understanding of how electrode parameters relate to the change of the voltage gradient distribution throughout the heart, which may help lead to optimal defibrillator design. DefibViz; is significant, in that, it is built by using an open-source graphics and visualization framework providing a platform for subsequent modifiability and extensibility. Moreover, it integrates simulation and visualization techniques, which previously required the running of several independent software executables, into an enhanced, seamless, and comprehensive software application.
Assuntos
Cardioversão Elétrica , Eletrodos , Software , Simulação por ComputadorAssuntos
Neoplasias da Mama/patologia , Matriz Extracelular/metabolismo , Fibronectinas/metabolismo , Neoplasias de Tecido Muscular/patologia , Citoesqueleto de Actina/ultraestrutura , Adulto , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/metabolismo , Neoplasias da Mama/cirurgia , Retículo Endoplasmático Rugoso/ultraestrutura , Matriz Extracelular/ultraestrutura , Feminino , Humanos , Muco/metabolismo , Neoplasias de Tecido Muscular/metabolismo , Neoplasias de Tecido Muscular/cirurgia , FenótipoRESUMO
Few studies have assessed longitudinal changes in circulating cytokine levels during normal pregnancy. We have examined the natural history of maternal plasma cytokines from early- to mid-pregnancy in a large, longitudinal cohort. Multiplex flow cytometry was used to measure interleukin (IL)-2, IL-6, IL-12, tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma and granulocyte-macrophage colony-stimulating factor (GM-CSF) in early- (median [IQR]: 8.5 weeks [7.1, 10.0]) and mid-pregnancy (25.0 [24.1, 26.1]) from 1274 Danish women delivering singleton term infants. GM-CSF decreased from early- to mid-pregnancy (median percent change [95% CI]: -51.3% [-59.1%, -41.8%]), while increases were observed in IL-6 (24.3% [4.6%, 43.9%]), IL-12 (21.3% [8.9%, 35.7%]) and IFN-gamma (131.7% [100.2%, 171.6%]); IL-2 (-2.8% [-11.5%, 0.0%]) and TNF-alpha (0% [-5.9%, 25.6%]) remained stable. Positive correlations were found between all cytokines, both in early- and mid-pregnancy (all p<0.001). Early- and mid-pregnancy levels were rank-correlated for IL-2, IL-12, TNF-alpha and GM-CSF, but not IL-6 and IFN-gamma; these correlations were generally weaker than correlations between different cytokines at a single time point in pregnancy. Women with a pre-pregnancy BMI <18.5 had reduced levels of IFN-gamma and GM-CSF compared to women in other BMI categories, while women aged >or=35 years had elevated IL-2, IL-6, TNF-alpha and IFN-gamma. Early-pregnancy levels of TNF-alpha were higher in women with a prior preterm delivery. Cytokine levels were not associated with gravidity. In conclusion, cytokines were detected in plasma during early- and mid-pregnancy, with IL-6, IL-12, IFN-gamma and GM-CSF concentrations varying over pregnancy. Concentrations may depend on BMI, maternal age and prior preterm delivery.
Assuntos
Citocinas/sangue , Citocinas/imunologia , Gravidez/sangue , Adulto , Fatores Etários , Índice de Massa Corporal , Dinamarca , Feminino , Idade Gestacional , Fator Estimulador de Colônias de Granulócitos e Macrófagos/sangue , Fator Estimulador de Colônias de Granulócitos e Macrófagos/imunologia , Humanos , Interferon gama/sangue , Interferon gama/imunologia , Interleucina-12/sangue , Interleucina-12/imunologia , Interleucina-2/sangue , Interleucina-2/imunologia , Interleucina-6/sangue , Interleucina-6/imunologia , Trabalho de Parto Prematuro/imunologia , Primeiro Trimestre da Gravidez/imunologia , Fatores de Tempo , Fator de Necrose Tumoral alfa/sangue , Fator de Necrose Tumoral alfa/imunologiaRESUMO
The success rate of direct current cardioversion (DCC), the most common method to convert atrial fibrillation (AF) to sinus rhythm (SR), depends on various factors including AF duration, prior anti-arrhythmic therapy, electrode position and size, transthoracic impedance, and the use of biphasic versus monophasic shocks. Recent, small clinical studies have reported using quadruple electrodes to deliver higher energy, in order to increase DCC success rates in refractory patients. This study aims to computationally model and compare double shock defibrillation with conventional single shock DCC, based on the two parameters, defibrillation threshold (DFT) and heterogeneity index (HI). DFT is the energy required to achieve a voltage gradient of 5 V/cm over 95% of the atrial myocardium. HI, calculated as the (95(th)-5(th))/50(th) percentile of atrial electric field magnitudes, is a measure of non-uniformity. The electric field distributions in the myocardium were generated for over five thousand different conventional and quadruple electrode placements with electrodes of two different sizes. Results show that there is a significant decrease in DFT (p0.01) and HI (p0.01) with increase in electrode size and quantity.
Assuntos
Fibrilação Atrial/terapia , Cardioversão Elétrica/métodos , Modelos Cardiovasculares , Fibrilação Atrial/fisiopatologia , Engenharia Biomédica , Simulação por Computador , Cardioversão Elétrica/instrumentação , Cardioversão Elétrica/estatística & dados numéricos , Eletrodos , Fenômenos Eletrofisiológicos , Análise de Elementos Finitos , Humanos , Imageamento TridimensionalRESUMO
OBJECTIVES: This study evaluated the cost effectiveness of adalimumab vs conventional therapy in patients with active ankylosing spondylitis (AS). METHODS: The analysis was based on pooled data from two Phase III studies of adalimumab in active AS. Patients with an inadequate response to >/=1 NSAID received adalimumab 40 mg every other week (n = 246) or placebo (n = 151) for 24 weeks. A microsimulation model was developed with patients being treated with adalimumab according to the International ASAS Consensus Statement and BSR guidelines. The pooled adalimumab data, as well as data from the Outcome Assessment in AS International Study (OASIS) database and the literature, were used to model patients' BASDAI and BASFI scores and costs and health-related quality of life associated with various degrees of disease activity. Costs (in 2004 British pound) of AS, drug, administration, monitoring, hospitalization and AEs were calculated from the perspective of the UK NHS. Discounting was applied at 3.5% per year for costs and benefits as per the NICE reference case for economic evaluations. Uncertainty was addressed via sensitivity analyses. RESULTS: The incremental cost-effectiveness ratio (ICER) of adalimumab vs conventional therapy was estimated to improve with longer time horizons (48 weeks to 5 and 30 yrs). The central estimate was that, over 30 yrs, adalimumab therapy yielded 1.03 more quality-adjusted life-years (QALYs) per patient initiating therapy. Some AS treatment-related costs were estimated to be offset by adalimumab (at 10,750 pounds/patient), leaving a total incremental cost (adalimumab vs conventional therapy) at 23,857 pounds per patient. The 30-yr ICER of adalimumab vs conventional therapy was estimated at 23 pounds 097/QALY. Sensitivity analyses demonstrated robustness of results. When indirect costs were also included (analysis from societal perspective), ICER improved to 5093 pounds/QALY. CONCLUSIONS: This analysis indicates that adalimumab, when used according to UK treatment guidelines, is cost-effective vs conventional therapy for treating AS patients.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Antirreumáticos/uso terapêutico , Espondilite Anquilosante/tratamento farmacológico , Espondilite Anquilosante/economia , Adalimumab , Adulto , Anticorpos Monoclonais/economia , Anticorpos Monoclonais Humanizados , Antirreumáticos/economia , Ensaios Clínicos Fase III como Assunto , Análise Custo-Benefício , Custos de Medicamentos/estatística & dados numéricos , Monitoramento de Medicamentos/métodos , Feminino , Custos de Cuidados de Saúde/estatística & dados numéricos , Humanos , Masculino , Guias de Prática Clínica como Assunto , Anos de Vida Ajustados por Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Sensibilidade e Especificidade , Índice de Gravidade de Doença , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Reino UnidoRESUMO
Pigeon circovirus (picv) was detected in cloacal swab samples by means of a newly-developed, sensitive pcr. An initial investigation of 17 Belgian racing pigeons aged up to eight months showed that rates of detection of 88 per cent and above were achieved using samples of cloacal swab, blood and bursa of Fabricius. The sampling of 15 caged pigeons six times when they were from three to 31 weeks of age indicated that picv infections were more readily detected in cloacal swabs than in blood, and that the virus could be detected in cloacal swabs for longer periods after infection than in blood. picv infections were detected in cloacal swabs from 38 of 47 young pigeons aged from two to 31 weeks, from 12 racing lofts, which had clinical signs including diarrhoea and weight loss, regurgitation and respiratory signs. Samples from birds from two infected lofts indicated that picv could be detected in some birds for at least 27 weeks. Although nine of 14 pigeons aged from 32 to 45 weeks were virus-positive, picv was detected in only one of 18 adult pigeons that originated from four infected lofts.
Assuntos
Infecções por Circoviridae/veterinária , Circovirus/isolamento & purificação , Cloaca/virologia , Columbidae/virologia , Doenças das Aves Domésticas/diagnóstico , Fatores Etários , Animais , Bélgica/epidemiologia , Bolsa de Fabricius/virologia , Infecções por Circoviridae/diagnóstico , Infecções por Circoviridae/epidemiologia , Infecções por Circoviridae/prevenção & controle , Reação em Cadeia da Polimerase/métodos , Reação em Cadeia da Polimerase/veterinária , Doenças das Aves Domésticas/epidemiologia , Doenças das Aves Domésticas/prevenção & controle , Estudos SoroepidemiológicosRESUMO
Nineteen racing pigeons aged from one to five years were examined postmortem. pcr tests showed that the spleens of 16 of them were positive for pigeon circovirus, the livers of six were positive, and blood from one of them was positive for the virus. Five of 44 embryos in embryonated eggs collected from three lofts were positive by pcr, but swabs taken from the crops of 64 adult birds which were feeding one- to 10-day-old squabs in these three lofts were negative for the viral dna.
Assuntos
Doenças das Aves/transmissão , Infecções por Circoviridae/veterinária , Circovirus/isolamento & purificação , Columbidae/virologia , Animais , Doenças das Aves/virologia , Bolsa de Fabricius/virologia , Infecções por Circoviridae/transmissão , Infecções por Circoviridae/virologia , Columbidae/embriologia , DNA Viral/análise , Embrião não Mamífero/virologia , Fígado/patologia , Fígado/virologia , Reação em Cadeia da Polimerase/métodos , Reação em Cadeia da Polimerase/veterinária , Baço/patologia , Baço/virologia , Viremia/veterinária , Viremia/virologiaRESUMO
OBJECTIVES: To review the literature relevant to microsporidial infection of muscle and to describe a case of human microsporidial infection involving both skeletal and cardiac muscle. METHODS: Samples from an AIDS patient with myositis have been examined by light and electron microscopy. RESULTS: We describe the findings at autopsy of a 47 year old Australian male with late stage AIDS, who had skeletal and cardiac muscle involvement with the microsporidian Trachipleistophora hominis. This is the third definitively identified case of human T. hominis infection and the first to describe infection of the myocardium. CONCLUSIONS: Microsporidial infection of muscle is rare in humans, but more work is needed to elucidate both the organisms and routes of transmission of this group of parasitic protozoa.
Assuntos
Infecções por HIV/complicações , Microsporídios/isolamento & purificação , Microsporidiose/complicações , Músculo Esquelético/parasitologia , Miocardite/parasitologia , Miosite/parasitologia , Infecções Oportunistas Relacionadas com a AIDS/parasitologia , Autopsia , Coração/parasitologia , Humanos , Masculino , Microsporidiose/parasitologia , Pessoa de Meia-Idade , Músculos Peitorais/parasitologiaRESUMO
We use optical darkfield micro-spectroscopy to characterize the plasmon resonance of individual silver nanoparticles in the presence of a substrate. The optical system permits multiple individual nanoparticles to be identified visually for simultaneous spectroscopic study. For silver particles bound to a silanated glass substrate, we observe changes in the Plasmon resonance due to induced variations in the local refractive index. The shifts in the plasmon resonance are investigated using a simple analytical theory in which the contributions from the substrate and environment are weighted with distance from the nanoparticle. The theory is compared with experimental results to determine a weighting factor which facilitates modeling of environmental refractive index changes using standard Mie code. Use of the optical system for characterizing nanoparticles attached to substrates for biosensing applications is discussed.
RESUMO
There has been a resurgence of interest in medical protozoology in the last twenty years or so mainly as a result of the recognition of HIV infection and the opportunistic protozoan infections associated with it. Many new species of microsporidia have been recognised as parasites causing human disease and several rare infections, such as isosporiasis, have become more commonly recognised, even in temperate climates. Some of the infections seen in temperate regions have arrived through foreign travel (tourism, work or immigration), sometimes exacerbated by immunosuppression (due to HIV, organ transplantation or malignancy). Importation of food from around the world and climate change (global warming) may also be contributing to the increase in previously rare protozoan infections now being seen in temperate regions. This article reviews the current status of these new and re-emerging human protozoan infections in temperate, rather than tropical locations.
Assuntos
Clima , Doenças Transmissíveis Emergentes/patologia , Infecções por Protozoários/patologia , Europa (Continente) , HumanosRESUMO
BACKGROUND: In early 2002 reports of outbreaks of gastroenteritis reached unprecedented levels in the UK. Forty five Norovirus outbreaks were reported in January 2002. OBJECTIVES: The objective of the study was to determine whether the outbreaks were Noroviral in origin and if so whether they represented a homogeneous or heterogeneous collection of Noroviruses by applying EIA and sequence analysis to representative faecal samples. STUDY DESIGN: Faecal specimens were collected during the week of highest incidence from 21 outbreaks in a variety of health care settings including hospitals and nursing homes. The outbreaks occurred in geographically distinct regions of the UK and samples were collected by reference laboratories in Glasgow, Manchester, Bristol and Southampton. RESULTS: The samples were all positive for Noroviruses by negative stain electron microscopy (EM) and Lordsdale virus (LV) EIA, therefore reverse transcriptase polymerase chain reaction (RT-PCR) amplification and nucleotide sequencing of the Norovirus RNA polymerase gene was performed on amplicons from samples of each of the 21 outbreaks to investigate the nature and extent of diversity. All samples were very closely related to the reference Lordsdale virus genome sequence. LV was first discovered during an hospital outbreak of gastroenteritis in Southampton General Hospital in March 1993. CONCLUSIONS: Noroviruses are a major cause of outbreaks of gastroenteritis in health care settings. LV is the predominant Norovirus in the UK and was detected in outbreaks that occurred during the national peak of gastroenteritis reports in January 2002.
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Infecções por Caliciviridae/epidemiologia , Surtos de Doenças , Gastroenterite/epidemiologia , Norovirus/isolamento & purificação , Sequência de Aminoácidos , RNA Polimerases Dirigidas por DNA/química , RNA Polimerases Dirigidas por DNA/genética , Fezes/virologia , Humanos , Técnicas Imunoenzimáticas , Dados de Sequência Molecular , Norovirus/classificação , Norovirus/genética , Análise de Sequência de DNA , Reino Unido/epidemiologiaRESUMO
Placement of external electrodes can significantly affect the success rate of transthoracic atrial defibrillation, but studies have not led to agreement on optimal electrode placements. This study aims to (1) develop an anatomically realistic, finite element model of the human torso for external atrial defibrillation, (2) investigate model parameters of skeletal muscle conductivity and anisotropy and the presence of subcutaneous fat, and (3) investigate clinical defibrillation parameters of electrode size, shape, and location. The model predicts atrial defibrillation threshold (ADFT) energy by requiring a voltage gradient of 5 V/cm over at least 95% of atrial myocardium. The model compares favorably with a clinical study of 301 patients that reported an anterior-posterior electrode position required approximately 20% less energy than an anterior-anterior position. Results indicate that a change in electrode size has a different effect for different electrode placements. This study finds that variation in electrode placement by only a few centimeters can change ADFTs by up to 51%. This is the first computer model of transthoracic atrial defibrillation to our knowledge. Our computer model is not limited to a few empirically selected electrode placements as in clinical studies and can test any location, size, and number of electrode placements.
RESUMO
It is still unclear what fundamental criteria influence the ability of alternating current (AC) to induce ventricular fibrillation (VF) in vivo. As the VF threshold has a bowl-shaped relationship with frequency (showing a minimum threshold at some frequency), similar to the nervous system, one proposed model has assumed that the mechanisms underlying AC stimulation of nerves are at work for VF induction. More recent work has suggested a second approach, whereby a simple RC-like model is sufficient to understand the cardiac AC stimulation threshold's frequency dependence, suggesting that some unarticulated mechanism is at work for VF. The paper directly tests these two models. In 12 intact dogs and 20 intact guinea pigs, DC pulses were used to stimulate AC square and AC sine waves at 10, 20, 40, 80 and 160 Hz. All electrodes were endocardial, with the return electrode being on a paw or thorax. It was found that, for square and sine wave stimulation in both dogs and guinea pigs, the stimulation threshold increased monotonically with frequency from 10 Hz up to 160 Hz (p < 0.01 for dogs and guinea pigs). Between 80 and 160 Hz, the AC stimulation threshold doubled, exactly as predicted by an RC model. It was concluded that the AC stimulation threshold is not bowl-shaped and is best understood with an RC model. As the VF threshold does exhibit a bowl-shape with frequency, as opposed to the stimulation threshold which does not, the VF induction frequency dependence must have different origins.
Assuntos
Eletricidade/efeitos adversos , Modelos Cardiovasculares , Fibrilação Ventricular/etiologia , Animais , Cães , Estimulação Elétrica/métodos , Segurança de Equipamentos , CobaiasRESUMO
Epithelial-myofibroblast transformation has been argued as playing a role in tubulo-interstitial fibrosis. To investigate this hypothesis, we examined 9 renal biopsy specimens from patients with chronic renal disease by light and electron microscopy. In all cases, electron microscopy confirmed light microscope observations in relation to tubulo-interstitial fibrosis-tubular atrophy, accumulation of extracellular matrix and of mesenchymal interstitial cells, and infiltration by inflammatory cells. Tubular epithelial cells (TECs) contained bundles of actin filaments: mostly lacking the focal densities typical of smooth-muscle myofilaments. The interstitium contained collagen and inflammatory cells. Some endothelial cells showed bundles of myofilaments. Free mesenchymal cells in the matrix were spindled and had sparse rough endoplasmic reticulum (rER), small attachment plaques, few actin filaments and no lamina. In one case, myofibroblasts (defined by abundant rER, myofilaments and fibronexuses) were present. Most of the mesenchymal cells, therefore, did not correspond to myofibroblasts, nor to classical fibroblasts because of the sparse rER and the presence of actin filaments. We therefore called these cells myoid stromal cells, regarding them as stromal mesenchymal elements showing partial activation towards a smooth-muscle phenotype. This paper demonstrates a greater phenotypic complexity of actin-containing stromal cells in the interstitium than previously appreciated, with only a minority conforming to true or fully differentiated myofibroblasts. The widespread presence of actin (as filaments or immunoreactivity) in both TECs and interstitial cells, combined with the absence of evidence of intermediate forms or of migration from epithelium into interstitium, may point to epithelium and interstitium as separate targets for actin upregulation as an alternative hypothesis to epithelial-myofibroblast transformation.
Assuntos
Citoesqueleto de Actina/ultraestrutura , Células Epiteliais/patologia , Fibroblastos/ultraestrutura , Fibrose/patologia , Túbulos Renais/patologia , Nefrite Intersticial/patologia , Citoesqueleto de Actina/metabolismo , Diferenciação Celular , Células Epiteliais/metabolismo , Fibroblastos/metabolismo , Fibrose/metabolismo , Humanos , Túbulos Renais/metabolismo , Microscopia Eletrônica , Microscopia de Fluorescência , Nefrite Intersticial/metabolismoRESUMO
A commercially available enzyme immunoassay, the IDEIA Norwalk-like virus (NLV) enzyme linked immunosorbent assay (ELISA; Dako Cytomation, Ely, UK) for detecting NLV antigen in faecal samples and determining the NLV genogroup was evaluated. The performance of the ELISA was compared with that of electron microscopy and the reverse transcription polymerase chain reaction by testing a panel of faecal samples collected from patients involved in outbreaks of gastroenteritis. When compared with reverse transcription-polymerase chain reaction (RT-PCR), the ELISA had a sensitivity and specificity of 55.5 and 98.3%, respectively. This compares with a sensitivity and specificity for EM of 23.9 and 99.2%, respectively. The sensitivity and specificity of the ELISA for determining the aetiology of a Norwalk virus-like outbreak, based on two or more positive samples within an outbreak, were 52.2 and 100% when two samples were collected from an outbreak and 71.4 and 100% when six or more samples were collected. The ELISA correctly identified the NLV genogroups of viruses previously characterised by partial DNA sequencing. The ELISA is a suitable alternative to the preliminary screening by EM for investigating outbreaks of gastroenteritis. Outbreaks, negative by ELISA should be examined by RT-PCR in order to detect strains non-reactive in the assay and virus strains from representative ELISA positive outbreaks should be characterised fully to allow the genetic diversity of NLVs co-circulating in the population to be described.
Assuntos
Antígenos Virais/análise , Infecções por Caliciviridae/virologia , Ensaio de Imunoadsorção Enzimática , Fezes/virologia , Gastroenterite/virologia , Norovirus/isolamento & purificação , Kit de Reagentes para Diagnóstico , Infecções por Caliciviridae/epidemiologia , Proteínas do Capsídeo/análise , Proteínas do Capsídeo/genética , Proteínas do Capsídeo/imunologia , Surtos de Doenças , Gastroenterite/epidemiologia , Genótipo , Humanos , Microscopia Eletrônica , Norovirus/classificação , Norovirus/genética , Norovirus/imunologia , RNA Viral/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Sensibilidade e EspecificidadeRESUMO
BACKGROUND AND AIMS: Factors that induce luminal bacteria to cross the intestinal epithelium following injury remain poorly defined. The aim of this study was to investigate the interaction between glutamine metabolism, energy supply, and inflammatory mediators in determining the translocation of non-pathogenic bacteria across cultured enterocytes. METHODS: The effect of tumour necrosis factor alpha (TNF-alpha) on translocation of Escherichia coli C25 across Caco-2 epithelial monolayers was studied in the presence of products and inhibitors of glutamine metabolism. Simultaneous measurements of transepithelial electrical resistance (TEER) and flux of lucifer yellow were used to assess effects on the paracellular pathway. Lactate dehydrogenase release was used to monitor enterocyte integrity. Imaging of monolayers in these experimental conditions was undertaken with transmission electron microscopy. RESULTS: Exposure to basolateral TNF-alpha (20 ng/ml) for six hours induced translocation of E coli across Caco-2 but only if accompanied by simultaneous glutamine depletion (p<0.01). Translocation was inhibited by addition of glutamine for two hours (p<0.01) but not by an isonitrogenous mixture of non-glutamine containing amino acids. Inhibition of glutamine conversion to alpha-ketoglutarate, but not blockade of glutathione or polyamine synthesis, also induced translocation in the presence of TNF-alpha. Manipulations that induced bacterial translocation were associated with a marked reduction in enterocyte ATP levels. No effect of these treatments on paracellular permeability or lactate dehydrogenase release was observed. Conditions in which translocation occurred were associated with the presence of bacteria within enterocyte vacuoles but not the paracellular space. CONCLUSIONS: In inflammatory conditions, the availability of glutamine as an enterocyte fuel substrate is essential for the preservation of a functional barrier to microorganisms. In conditions of acute glutamine depletion, cytokine mediated bacterial translocation appears to be primarily a transcellular process.