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OBJECTIVE: Fetal growth restriction (FGR) is a major risk factor for stillbirth and most commonly arises from uteroplacental insufficiency. Despite clinical examination and third-trimester fetal biometry, cases of FGR often remain undetected antenatally. Placental insufficiency is known to be associated with altered blood flow resistance in maternal, placental and fetal vessels. The aim of this study was to evaluate the performance of individual and combined Doppler blood flow resistance measurements in the prediction of term small-for-gestational age and FGR. METHODS: This was a prospective study of 347 nulliparous women with a singleton pregnancy at 36 weeks' gestation in which fetal growth and Doppler measurements were obtained. Pulsatility indices (PI) of the uterine arteries (UtA), umbilical artery (UA) and fetal vessels were analyzed, individually and in combination, for prediction of birth weight < 10th , < 5th and < 3rd centiles. Doppler values were converted into centiles or multiples of the median (MoM) for gestational age. The sensitivities, positive and negative predictive values and odds ratios (OR) of the Doppler parameters for these birth weights at â¼ 90% specificity were assessed. Additionally, the correlations between Doppler measurements and other measures of placental insufficiency, namely fetal growth velocity and neonatal body fat measures, were analyzed. RESULTS: The Doppler combination most strongly associated with placental insufficiency was a newly generated parameter, which we have named the cerebral-placental-uterine ratio (CPUR). CPUR is the cerebroplacental ratio (CPR) (middle cerebral artery PI/UA-PI) divided by mean UtA-PI. CPUR MoM detected FGR better than did mean UtA-PI MoM or CPR MoM alone. At â¼ 90% specificity, low CPUR MoM had sensitivities of 50% for birth weight < 10th centile, 68% for < 5th centile and 89% for < 3rd centile. The respective sensitivities of low CPR MoM were 26%, 37% and 44% and those of high UtA-PI MoM were 34%, 47% and 67%. Low CPUR MoM was associated with birth weight < 10th centile with an OR of 9.1, < 5th centile with an OR of 17.3 and < 3rd centile with an OR of 57.0 (P < 0.0001 for all). CPUR MoM was also correlated most strongly with fetal growth velocity and neonatal body fat measures, as compared with CPR MoM or UtA-PI MoM alone. CONCLUSIONS: In this cohort, a novel Doppler variable combination, the CPUR (CPR/UtA-PI), had the strongest association with indicators of placental insufficiency. CPUR detected more cases of FGR than did any other Doppler parameter measured. If these results are replicated independently, this new parameter may lead to better identification of fetuses at increased risk of stillbirth that may benefit from obstetric intervention. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.
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Retardo del Crecimiento Fetal/diagnóstico por imagen , Arteria Cerebral Media/fisiopatología , Insuficiencia Placentaria/fisiopatología , Ultrasonografía Prenatal , Arteria Uterina/fisiopatología , Adulto , Biometría , Femenino , Retardo del Crecimiento Fetal/fisiopatología , Edad Gestacional , Humanos , Arteria Cerebral Media/diagnóstico por imagen , Valor Predictivo de las Pruebas , Embarazo , Tercer Trimestre del Embarazo , Estudios Prospectivos , Valores de Referencia , Arteria Uterina/diagnóstico por imagenRESUMEN
Leigh syndrome (LS) associated with cytochrome c oxidase (COX) deficiency is an early onset, fatal mitochondrial encephalopathy, leading to multiple neurological failure and eventually death, usually in the first decade of life. Mutations in SURF1, a nuclear gene encoding a mitochondrial protein involved in COX assembly, are among the most common causes of LS. LSSURF1 patients display severe, isolated COX deficiency in all tissues, including cultured fibroblasts and skeletal muscle. Recombinant, constitutive SURF1-/- mice show diffuse COX deficiency, but fail to recapitulate the severity of the human clinical phenotype. Pigs are an attractive alternative model for human diseases, because of their size, as well as metabolic, physiological and genetic similarity to humans. Here, we determined the complete sequence of the swine SURF1 gene, disrupted it in pig primary fibroblast cell lines using both TALENs and CRISPR/Cas9 genome editing systems, before finally generating SURF1-/- and SURF1-/+ pigs by Somatic Cell Nuclear Transfer (SCNT). SURF1-/- pigs were characterized by failure to thrive, muscle weakness and highly reduced life span with elevated perinatal mortality, compared to heterozygous SURF1-/+ and wild type littermates. Surprisingly, no obvious COX deficiency was detected in SURF1-/- tissues, although histochemical analysis revealed the presence of COX deficiency in jejunum villi and total mRNA sequencing (RNAseq) showed that several COX subunit-encoding genes were significantly down-regulated in SURF1-/- skeletal muscles. In addition, neuropathological findings, indicated a delay in central nervous system development of newborn SURF1-/- piglets. Our results suggest a broader role of sSURF1 in mitochondrial bioenergetics.
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Sistema Nervioso Central/crecimiento & desarrollo , Modelos Animales de Enfermedad , Enfermedad de Leigh/genética , Proteínas de la Membrana/genética , Proteínas Mitocondriales/genética , Sus scrofa/genética , Animales , Animales Modificados Genéticamente , Animales Recién Nacidos , Conducta Animal , Sistemas CRISPR-Cas , Células Cultivadas , Regulación hacia Abajo , Complejo IV de Transporte de Electrones/metabolismo , Femenino , Fibroblastos , Edición Génica , Técnicas de Inactivación de Genes , Humanos , Yeyuno/patología , Enfermedad de Leigh/patología , Masculino , Mitocondrias/patología , Músculo Esquelético/citología , Músculo Esquelético/patología , Técnicas de Transferencia Nuclear , Cultivo Primario de CélulasRESUMEN
Sessile water droplet evaporation in varied gravity and electric fields has been experimentally studied. Specifically, the influences of gravity and electric fields are investigated in the context of the heat flux distribution beneath the droplets, as well as the droplet mechanics and resulting shapes. Experimental testing was carried out during a European Space Agency (ESA) Parabolic Flight Campaign (PFC 66). The droplets tested evaporated with a pinned contact line, a single wettability condition, and varied droplet volume and substrate heat flux. The peak heat transfer was located at the contact line for all cases. The peak heat flux, average heat flux, and droplet evaporation rate were shown to vary strongly with gravity, with higher values noted for hypergravity conditions and lower values in microgravity conditions. The droplet thermal inertia was shown to play a significant role, with larger droplets taking more time to reach thermal equilibrium during the parabolic testing period. No significant impact of the electric field on the droplet evaporation was noted for these test conditions.
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The characteristic imaging finding common to Joubert syndrome and related disorders is the 'molar tooth' sign. The prenatal diagnosis of Joubert syndrome using both ultrasound and fetal magnetic resonance imaging (MRI) in families with an affected child has been reported previously. We report two cases in which the molar tooth sign was identified by sonography at 26 + 4 weeks and at 20 + 6 weeks, respectively, prior to fetal MRI or genetic testing. In both cases the finding was subsequently confirmed on fetal MRI. As definitive prenatal genetic testing may not be conclusive in Joubert syndrome, the ability to identify the molar tooth sign sonographically before 24 weeks provides a valuable adjunct to prenatal diagnosis.
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Anomalías Múltiples/diagnóstico por imagen , Encéfalo/patología , Enfermedades Cerebelosas/diagnóstico por imagen , Ecoencefalografía , Anomalías del Ojo/diagnóstico por imagen , Enfermedades Renales Quísticas/diagnóstico por imagen , Ultrasonografía Prenatal , Anomalías Múltiples/patología , Adulto , Encéfalo/anomalías , Encéfalo/embriología , Enfermedades Cerebelosas/patología , Cerebelo/anomalías , Anomalías del Ojo/patología , Femenino , Humanos , Enfermedades Renales Quísticas/patología , Imagen por Resonancia Magnética , Embarazo , Resultado del Embarazo , Diagnóstico Prenatal , Retina/anomalías , Retina/diagnóstico por imagen , Retina/patologíaRESUMEN
BACKGROUND: Eosinophil accumulation in the lung is an important feature of airway inflammation in asthma. There is therefore much interest in developing novel therapies to prevent this process. Accumulating evidence suggests that statins have anti-inflammatory properties, including inhibition of leucocyte accumulation. We therefore assessed the ability of five statins to inhibit human eosinophil adhesion to recombinant human inter-cellular adhesion molecule (rhICAM)-1 under physiologically relevant flow conditions. METHODS: Purified eosinophils were pre-treated with a panel of statins before elucidation of the adhesion profiles of resting and granulocyte macrophage-colony stimulating factor (GM-CSF)-stimulated cells to rhICAM-1-coated microchannels at a flow rate of 0.5 dynes/cm(2). Images were recorded in real-time at 1 min intervals and analysed using Ducocell software. RESULTS: Fluvastatin and lovastatin (both 10 nm) significantly inhibited GM-CSF-stimulated eosinophil adhesion to rhICAM-1 after 2 min (34.4+/-3.0% inhibition and 37.8+/-12.6% inhibition, respectively, n=4, P<0.05) but had no significant inhibitory effect on unstimulated eosinophil adhesion. Mevastatin, simvastatin, and pravastatin (all 10 nm) had no significant effect on GM-CSF-stimulated eosinophil adhesion to rhICAM-1. A concentration range of fluvastatin and lovastatin inhibited GM-CSF stimulated eosinophil adhesion with significant (P<0.05) inhibition observed at low concentrations of 1 nm for both drugs. Mevalonate (100 nm) reversed fluvastatin-mediated but not lovastatin-mediated inhibition of eosinophil adhesion. CONCLUSIONS: Inhibition of eosinophil adhesion to ICAM-1 by fluvastatin and lovastatin under physiological shear stress represent novel actions by these drugs that may inform the development of anti-inflammatory therapy for allergic disease.
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Adhesión Celular/efectos de los fármacos , Eosinófilos/citología , Eosinófilos/efectos de los fármacos , Ácidos Grasos Monoinsaturados/farmacología , Factor Estimulante de Colonias de Granulocitos y Macrófagos/farmacología , Indoles/farmacología , Molécula 1 de Adhesión Intercelular/metabolismo , Lovastatina/farmacología , Microfluídica , Anticuerpos Monoclonales/inmunología , Anticuerpos Monoclonales/farmacología , Apoptosis/efectos de los fármacos , Forma de la Célula/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Eosinófilos/metabolismo , Fluvastatina , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Molécula 1 de Adhesión Intercelular/genética , Lovastatina/análogos & derivados , Antígeno de Macrófago-1/inmunología , Antígeno de Macrófago-1/metabolismo , Ácido Mevalónico/farmacología , Técnicas Analíticas Microfluídicas , Pravastatina/farmacología , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Simvastatina/farmacología , Molécula 1 de Adhesión Celular Vascular/genética , Molécula 1 de Adhesión Celular Vascular/metabolismoRESUMEN
Hematologic and coagulation studies were conducted on Atlantic bottlenose dolphins and killer whales. Hematologic values were similar to those in man. These animals differed from other mammals in that the Hageman factor (factor XII) was absent and this absence caused marked prolongation of coagulation. Levels of factors VIII and V were high and those of VII and X were low compared with levels in man.
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Cetáceos , Factor XII/análisis , Animales , Pruebas de Coagulación Sanguínea , Factor V/análisis , Factor VII/análisis , Factor VIII/análisis , Factor X/análisis , Tiempo de ProtrombinaRESUMEN
OBJECTIVES: To determine what proportion of men who have sex with men (MSM) attending genitourinary medicine (GUM) clinics are offered and accept an HIV test and to examine clinic and patient characteristics associated with offer and uptake. METHODS: A cross-sectional study of all GUM clinics in the United Kingdom, involving a case note review of up to 30 patient records per clinic and the completion of a clinic policy form. RESULTS: Overall, 86% of MSM were offered a test and of those 82% accepted a test. Attending with symptoms of a sexually transmitted infection (STI), fewer numbers of partners in the past three months and having tested previously were all independently associated with a decreased likelihood of being offered a test. Attending with symptoms of an STI, increasing age, never having had a risk from unprotected anal intercourse or a previous HIV test and increasing time to wait for results were all independently associated with a decreased likelihood of a patient accepting a test. Only a quarter of clinics reported a written policy for HIV testing intervals among MSM; however, all clinics reported offering testing to all new MSM patients at first screening. The testing policy for re-attending patients was less clear. CONCLUSIONS: Testing must reach those at most risk and those less likely to test in order to reduce further the proportion of undiagnosed HIV infection. This study suggests that opportunities to detect infection may be being missed and a move towards universal testing of all MSM attending with a new episode, as well as testing within the window period, is recommended.
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Atención Ambulatoria/estadística & datos numéricos , Infecciones por VIH/diagnóstico , Homosexualidad Masculina , Aceptación de la Atención de Salud/estadística & datos numéricos , Adulto , Anciano , Estudios Transversales , Política de Salud , Accesibilidad a los Servicios de Salud , Humanos , Masculino , Persona de Mediana Edad , Política Organizacional , Reino UnidoRESUMEN
alpha-Mannosidosis is a lysosomal storage disorder resulting from a functional deficiency of the lysosomal enzyme alpha-mannosidase. This deficiency results in the accumulation of various oligosaccharides in the lysosomes of affected individuals, causing somatic pathology and progressive neurological degeneration that results in cognitive deficits, ataxia, and other neurological symptoms. We have a naturally occurring guinea pig model of this disease which exhibits a deficiency of lysosomal alpha-mannosidase and has a similar clinical presentation to human alpha-mannosidosis. Various tests were developed in the present study to characterise and quantitate the loss of neurological function in alpha-mannosidosis guinea pigs and to follow closely the progression of the disease. General neurological examinations showed progressive differences in alpha-mannosidosis animals from approximately 1 month of age. Significant differences were observed in hind limb gait width from 2 months of age and significant cognitive (memory and learning) deficits were observed from 3 months of age. Evoked response tests showed an increase in somatosensory P1 peak latency in alpha-mannosidosis guinea pigs from approximately 2 months of age, as well as progressive hearing loss using auditory brainstem evoked responses. The alpha-mannosidosis guinea pig therefore appears to exhibit many of the characteristics of the human disease, and will be useful in evaluating therapies for treatment of central nervous system pathology.
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Conducta Animal/fisiología , alfa-Manosidosis/fisiopatología , alfa-Manosidosis/psicología , Estimulación Acústica/métodos , Factores de Edad , Animales , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Estimulación Eléctrica/métodos , Electroencefalografía , Potenciales Evocados Auditivos del Tronco Encefálico/fisiología , Femenino , Marcha/fisiología , Cobayas , Masculino , Aprendizaje por Laberinto/fisiología , Examen Neurológico , Tiempo de Reacción , Factores Sexuales , alfa-Manosidasa/deficiencia , alfa-Manosidosis/genéticaRESUMEN
While most genitourinary (GU) medicine clinics achieve a high uptake for testing HIV in new patients, they may still miss testing those at highest risk. Point-of-care testing (POCT) and salivary samples are acceptable and feasible but have not yet been shown to increase uptake among high-risk patients (HRP). This study aimed to describe reasons why HRP decline HIV testing and whether offering POCT along with standard testing would increase the uptake of testing HIV in two London GU medicine clinics. Anonymous self-administered questionnaires were offered to all new and rebooked patients. Eight hundred and ninety-nine questionnaires were analysed of which 598 were HRP. Uptake of HIV testing was 77.1% among HRP and 65.8% among the rest. A total of 51.1% of HRP who declined HIV testing said they would be more likely to accept a POCT and 32.8% a salivary test. Introduction of rapid POCT for HIV would increase patient's choice and may increase the likelihood of HRP accepting an HIV test.
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Serodiagnóstico del SIDA , Infecciones por VIH/diagnóstico , Aceptación de la Atención de Salud , Sistemas de Atención de Punto , Encuestas y Cuestionarios , Instituciones de Atención Ambulatoria , Femenino , Heterosexualidad , Homosexualidad , Humanos , Londres , Masculino , Aceptación de la Atención de Salud/estadística & datos numéricos , Riesgo , Factores de Tiempo , Sistema UrogenitalRESUMEN
The Department of Health provided two recurrent targeted funding of 5 million pounds sterlings and 3 million pounds sterlings for genitourinary (GU) medicine services in 2003 in response to the increasing waiting times for appointments. The British Association for Sexual Health and HIV conducted a survey to find out if the clinics continued to receive their full allocation, if not, the reasons for it, and the workload change from 2002 to 2004. Out of a total of 91 responders, 78 were from acute trusts and 13 from primary care trusts (PCTs). Of the acute trusts and PCTs, respectively, 67.9% and 76.9% received the full allocation; overall 30.8% did not receive their full allocation. In all, 86% of clinics had increases in their workload and of the 26 clinics with shortfall of funds, 24 (92.3%) still managed to increase the workload. This survey showed that the funding and other measures have increased the workload capacity, and also highlights the continuing problem of many clinics in not receiving their full allocation. Such clinics should be targeted for early review by Medical Foundation for AIDS and Sexual Health with involvement of the Special Health Authorities and PCTs in the current national review of GU services.
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Financiación Gubernamental/organización & administración , Accesibilidad a los Servicios de Salud/economía , Enfermedades de Transmisión Sexual/economía , Enfermedades de Transmisión Sexual/prevención & control , Encuestas Epidemiológicas , Humanos , Enfermedades de Transmisión Sexual/epidemiología , Medicina EstatalRESUMEN
Of all cancer patients, 28% had gastrointestinal parasites of medical importance.
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Helmintiasis/epidemiología , Parasitosis Intestinales/epidemiología , Neoplasias/complicaciones , Infecciones por Protozoos/epidemiología , Animales , Heces/parasitología , Helmintiasis/parasitología , Infecciones por Uncinaria/epidemiología , Infecciones por Uncinaria/parasitología , Humanos , Parasitosis Intestinales/parasitología , Infecciones por Protozoos/parasitología , Estudios Retrospectivos , Uganda/epidemiologíaRESUMEN
Sebaceous naevus are associated with malignant transformation. They commonly occur in the head and neck region and are associated with malignant transformation into basal cell and squamous cell carcinomas. This case report describes a case of a malignant melanoma arising from a longstanding sebaceous naevus.
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Melanoma , Nevo Sebáceo de Jadassohn/patología , Neoplasias de las Glándulas Sebáceas , Anciano de 80 o más Años , Transformación Celular Neoplásica , Diagnóstico Diferencial , Humanos , Masculino , Melanoma/diagnóstico , Neoplasias de las Glándulas Sebáceas/diagnósticoRESUMEN
alpha-Mannosidosis is a lysosomal storage disease resulting from a deficiency of the enzyme alpha-D-mannosidase. A major feature of alpha-mannosidosis is progressive neurological decline, for which there is no safe and effective treatment available. We have a guinea pig model of alpha-mannosidosis that models the human condition. This study investigates the feasibility of implanting differentiated mouse embryonic stem cells in the neonatal guinea pig brain in order to provide a source of alpha-mannosidase to the affected central nervous system. Cells implanted at a low dose (1.5 x 10(3)cells per hemisphere) at 1 week of age were found to survive in very low numbers in some immunosuppressed animals out to 8 weeks. Four weeks post-implantation, cells implanted in high numbers (10(5) cells per hemisphere) formed teratomas in the majority of the animals implanted. Although implanted cells were found to migrate extensively within the brain and differentiate into mature cells of neural (and other) lineages, the safety issue related to uncontrolled cell proliferation precluded the use of this cell type for longer-term implantation studies. We conclude that the pluripotent cell type used in this study is unsuitable for achieving safe engraftment in the guinea pig brain.
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Encéfalo/citología , Supervivencia de Injerto/fisiología , Células Madre Multipotentes/citología , Trasplante de Células Madre/efectos adversos , alfa-Manosidosis/terapia , Animales , Diferenciación Celular , Movimiento Celular , Modelos Animales de Enfermedad , Cobayas , Inmunohistoquímica , Ratones , Microscopía Confocal , Trasplante de Células Madre/métodos , Teratoma/etiologíaRESUMEN
OBJECTIVES: To determine the seroprevalence and aspects of the epidemiology of canine adenovirus (CAdV) and canine herpesvirus (CaHV-1) in European red foxes (Vulpes vulpes) in Australia. DESIGN: Serum samples were collected opportunistically from foxes in 1991-1994 in Western Australia (WA) and South Australia (SA) and in 1980-1984 and 1990-1994 in New South Wales (NSW) and the Australian Capital Territory (ACT). The sera were examined for antibody to CAdV and CaHV-1 using ELISAs. Seroprevalence in the different regions was determined for both viruses and the CAdV data were analysed for interactions between decade of collection, age, season, region and gender using logistic regression. RESULTS: The overall prevalence of antibody to CAdV was 23.2% (308/1326) but was significantly higher in sera collected in the eastern states of Australia (47%: 233/498) than in WA (9%: 75/828). Overall, in NSW and the ACT, there was a significantly lower prevalence in juveniles than in adults and the prevalence in juveniles in the 1990s was significantly lower than in the 1980s. The prevalence was also significantly lower in the autumn than in the winter for juveniles but the reverse held for adults. The NSW and ACT data were subdivided into eastern (including the ACT) and western regions. This revealed a significantly higher prevalence in the winter than in the autumn for the west and the reverse in the east. In WA, the northern rangeland regions of WA had lower prevalence (1.9%) than the southern agriculture regions (10.7%). Seasonally, there was a peak prevalence in the spring dropping through the summer and autumn and rising again in the winter. This seasonal pattern was also found in the combined data for all sites in the 1990s. There was no gender difference in prevalence of CAdV either overall or in different regions. The overall prevalence of antibody to CaHV-1 was 2.2% (28/1300). The small number of positives allowed only limited statistical analysis that did not reveal any differences in decade of collection, age, season or region. CONCLUSIONS: CAdV infection is common in the Australian fox population whereas CaHV-1 infection is rare. For CAdV, the age and seasonal patterns of seroprevalence were generally consistent with the recruitment of young susceptible foxes into the population in the spring and the accumulation of infections with age. The differences in regional prevalences correlated with fox density. The low prevalence of antibody to CaHV-1 suggests that CaHV-1 may be a more suitable vector than CAdV for bait delivery of immunocontraceptive antigens to foxes in Australia.
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Infecciones por Adenoviridae/veterinaria , Adenovirus Caninos/aislamiento & purificación , Anticuerpos Antivirales/sangre , Zorros/virología , Infecciones por Herpesviridae/veterinaria , Herpesvirus Cánido 1/aislamiento & purificación , Infecciones por Adenoviridae/epidemiología , Adenovirus Caninos/inmunología , Animales , Anticuerpos Antivirales/análisis , Australia/epidemiología , Femenino , Infecciones por Herpesviridae/epidemiología , Herpesvirus Cánido 1/inmunología , Masculino , Estaciones del Año , Estudios SeroepidemiológicosRESUMEN
INTRODUCTION: Basal Cell Carcinomas are a condition commonly managed by Plastic Surgeons. National guidelines for their management where published in 2008. As part of revalidation, nine surgical subspecialities will publish individual surgeon outcome data for morbidity and mortality. Basal Cell Carcinoma incomplete excision rates have been postulated as an outcome measure for Plastic Surgeons. METHODS: We conducted a retrospective study of all Basal Cell Carcinomas within our unit from the 1st January to 31st December 2011. All patients were identified from the regional histopathology database and each histopathology report was analysed. Incomplete excisions were further analysed using a standard proforma. RESULTS: A total of 392 lesions were excised from 347 patients. In total there where 19 incompletely excised lesions with an overall incomplete excision rate of 4.8%. The temple area and inner canthus areas had the highest incidence of incomplete excision. Trainees encompassed 68% of all incompletely excised lesions. Histopathological analysis of the incompletely excised lesions showed that 60% of Consultant's incomplete excisions were morphoeic. Whereas for trainees, 54% were nodular, 30% infiltrative and the remainder morphoeic. Residual tumour was found in 36% of cases that were re-excised. No incompletely excised lesion that was followed up clinically, recurred after one year. CONCLUSIONS: The incomplete excision rate was low and comparable with other published studies in the literature. Individual surgeon outcome data based on incomplete excision rates for Basal Cell Carcinoma is meaningless unless the location of the lesion and the histopathological subtype have been adjusted for.
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Carcinoma Basocelular/cirugía , Neoplasias de Cabeza y Cuello/cirugía , Neoplasias Cutáneas/cirugía , Cirugía Plástica/normas , Carcinoma Basocelular/patología , Neoplasias de Cabeza y Cuello/patología , Humanos , Auditoría Médica , Cuerpo Médico de Hospitales/normas , Neoplasia Residual , Irlanda del Norte , Reoperación/estadística & datos numéricos , Estudios Retrospectivos , Neoplasias Cutáneas/patologíaRESUMEN
OBJECTIVE: Foetal CT has recently been added to the foetal imaging armamentarium, but this carries with it the risks of ionizing radiation, both to the mother and the foetus. Foetal "black bone" MRI is a new technique that allows assessment of the foetal skeleton without the risk of exposure to ionizing radiation and is a potential new sequence in foetal MRI examination. METHODS: Retrospective review of all foetal MRI studies over the past 4- to 5-year period identified 36 cases where susceptibility weighted imaging was used. Cases were selected from this group to demonstrate the potential utility of this sequence. RESULTS: This sequence is most frequently useful not only in the assessment of spinal abnormalities, most commonly the bony abnormalities in myelomeningocele, but also in cases of scoliosis, segmentation anomalies and sacrococcygeal teratoma. CONCLUSION: Although the utility of this sequence is still being evaluated, it provides excellent contrast between the mineralized skeleton and surrounding soft tissues compared with standard half Fourier acquisition single-shot turbo-spin echo sequences. Further assessment is required to determine whether black bone MRI can more accurately evaluate the level of bony defect in spina bifida aperta, an important prognostic factor. Potential further uses include the assessment of skeletal dysplasias, evaluation of the skull base and craniofacial skeleton in certain congenital anomalies and the post-mortem evaluation of the foetal skeleton potentially obviating the need for necropsy. ADVANCES IN KNOWLEDGE: Foetal black bone MRI can be performed using susceptibility weighted imaging and allows better demonstration of the mineralized skeleton compared with standard sequences.
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Enfermedades Fetales/diagnóstico , Imagen por Resonancia Magnética/métodos , Columna Vertebral/anomalías , Autopsia , Femenino , Humanos , Masculino , Embarazo , Diagnóstico Prenatal , Estudios Retrospectivos , Columna Vertebral/embriologíaRESUMEN
The purpose of this study was to map the initiation (tsp) and termination points of transcripts arising from an open reading frame (ORF3) found in the inverted terminal repeat of the orf virus genome and also, to identify probable transcriptional control sequences. Early transcripts of approx. 0.76 kb were mapped to ORF3 and found to be transcribed toward the ends of the genome. Using the S1 nuclease and primer-extension methods, the bulk of the tsp were mapped to a position 12-13 nucleotides (nt) downstream from a sequence which resembles A + T-rich vaccinia virus early promoters. The 5' ends were 81-82 nt upstream from the first ATG in ORF3. Most of 3' ends of the transcripts mapped to a region 24-32 nt downstream from a T5NT sequence found near the ORF3 stop codon. A second transcription termination point was found 25 nt downstream from another T5NT sequence located downstream and separated by 85 nt from the first. These results infer that the A + T-rich, early transcriptional control sequences found in other poxvirus genomes have been conserved in the G + C-rich genome of orf virus.
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Genes Virales , Virus del Orf/genética , Regiones Promotoras Genéticas , Regiones Terminadoras Genéticas , Transcripción Genética , Virus Vaccinia/genética , Secuencia de Aminoácidos , Secuencia de Bases , Northern Blotting , Regulación Viral de la Expresión Génica , Datos de Secuencia Molecular , Sistemas de Lectura Abierta , Mapeo Restrictivo , Moldes GenéticosRESUMEN
1. The mitogen-activated protein kinases (MAPKs) consist of the p42/p44 MAPKs and the stress-activated protein kinases, c-Jun N-terminal kinase (JNK) and p38 MAPK. In this study we have examined the effect of histamine H(1) receptor activation on MAPK pathway activation in the smooth muscle cell line DDT(1)MF-2. 2. Histamine stimulated time and concentration-dependent increases in p42/p44 MAPK activation in DDT(1)MF-2 cells. Responses to histamine were inhibited by the histamine H(1) receptor antagonist mepyramine (K(D) 3.5 nM) and following pre-treatment with pertussis toxin (PTX; 57% inhibition). 3. Histamine-induced increases in p42/p44 MAPK activation were blocked by inhibitors of MAPK kinase 1 (PD 98059), tyrosine kinase (genistein and tyrphostin A47), phosphatidylinositol 3-kinase (wortmannin and LY 294002) and protein kinase C (Ro 31-8220; 10 microM; 41% inhibition). Inhibitors of Src tyrosine kinase (PP2) and the epidermal growth factor tyrosine kinase (AG1478) were without effect. Removal of extracellular Ca(2+), chelation of intracellular Ca(2+) with BAPTA and inhibition of focal adhesion assembly (cytochalasin D) had no significant effect on histamine-induced p42/p44 MAPK activation. 4. Histamine stimulated time and concentration-dependent increases in p38 MAPK activation in DDT(1)MF-2 cells but had no effect on JNK activation. Histamine-induced p38 MAPK activation was inhibited by pertussis toxin (74% inhibition) and the p38 MAPK inhibitor SB 203580 (95% inhibition). 5. In summary, we have shown the histamine H(1) receptor activates p42/p44 MAPK and p38 MAPK signalling pathways in DDT(1)MF-2 smooth muscle cells. Interestingly, signalling to both pathways appears to involve histamine H(1) receptor coupling to G(i)/G(o)-proteins.