RESUMEN
Ancient schwannomas are benign tumours arising from the neural sheath of peripheral, cranial and autonomic nerves. They are commonly situated in the inner ear and spine with pelvic manifestations being rare. We present the case of a 30-year-old patient, who presented with an abdominal mass. MRI imaging suggested a broad ligament fibroid and open surgery was undertaken to remove it. Subsequent histology confirmed an ancient schwannoma. This case report details the rarity of such a condition and the need for a high index of suspicion as well as outlining management options and surveillance.
RESUMEN
Primary malignant bone tumours (PMBT) are rare. We have reviewed patient outcomes in Scotland over a 20 year period and provided an update on the principles of current management strategies for the non-specialist practitioner. The Scottish Managed Clinical Network for Sarcoma (MCN) connects the three main management centres for sarcoma in Scotland: Glasgow, Aberdeen and Edinburgh. Prior to the formation of the MCN, all centres were connected via the Scottish Bone Tumour Registry (SBTR), where they would meet on a quarterly basis and all the bone/soft tissue tumour cases were discussed retrospectively. The MCN was introduced in 2006. Our primary aims were to assess the impact of the MCN on patient outcomes and to update clinicians on the recognition, assessment and staging of PMBT. A secondary aim was to compare results from the Scottish centres with other UK sites. The patient information was gathered from the Scottish Bone Tumour Registry, held at the Queen Elizabeth University Hospital in Glasgow. All patients with diagnoses of Osteosarcoma, Chondrosarcoma and Ewing Sarcoma between 1994 and 2014 were included. Results showed that there was no significant change in outcome following the formation of the Scottish Managed Clinical Network for Sarcoma, and that there were little differences in outcome amongst the three major management centres in Scotland. Findings also show Scotland to have similar outcomes to that of the rest of the UK following diagnosis of a primary malignant bone tumour.
RESUMEN
Cryogenian cap carbonates that overlie Sturtian glacial deposits were formed during a post-glacial transgression. Here, we describe microfossils from the Kakontwe Formation of Zambia and the Taishir Formation of Mongolia-both Cryogenian age, post-Sturtian cap carbonates-and investigate processes involved in their formation and preservation. We compare microfossils from these two localities to an assemblage of well-documented microfossils previously described in the post-Sturtian Rasthof Formation of Namibia. Microfossils from both new localities have 10 ± 1 µm-thick walls composed of carbonaceous matter and aluminosilicate minerals. Those found in the Kakontwe Formation are spherical or ovoid and 90 ± 5 µm to 200 ± 5 µm wide. Structures found in the Taishir Formation are mostly spherical, 50 ± 5 µm to 140 ± 5 µm wide, with distinct features such as blunt or concave edges. Chemical and mineralogical analyses show that the walled structures and the clay fraction extracted from the surrounding sediments are composed of clay minerals, especially muscovite and illite, as well as quartz, iron and titanium oxides, and some dolomite and feldspar. At each locality, the mineralogy of the microfossil walls matched that of the clay fractions of the surrounding sediment. The abundance of these minerals in the walled microfossils relative to the surrounding carbonate matrix and microbial laminae, and the presence of minerals that cannot precipitate from solution (titanium oxide and feldspar), suggests that the composition represents the original mineralogy of the structures. Furthermore, the consistency in mineralogy of both microfossils and sediments across the three basins, and the uniformity of size and shape among mineral grains in the fossil walls indicate that these organisms incorporated these minerals by primary biological agglutination. The discovery of new, mineral-rich microfossil assemblages in microbially laminated and other fine-grained facies of Cryogenian cap carbonates from multiple localities on different palaeocontinents demonstrates that agglutinating eukaryotes were widespread in carbonate-dominated marine environments in the aftermath of the Sturtian glaciation.
Asunto(s)
Carbonatos/química , Eucariontes/aislamiento & purificación , Fósiles , Organismos Acuáticos/aislamiento & purificación , Sedimentos Geológicos/química , NamibiaRESUMEN
To investigate tumour progression mechanism in transgenic mouse skin carcinogenesis, inducible PTEN ablation (Δ5PTEN(flx)) was targeted to the epidermis of mice expressing activated ras(Ha)/fos oncogenes (HK1.ras and HK1.fos). RU486-treated HK1.ras/fos-Δ5PTEN(flx) epidermis exhibited significant keratinocyte proliferation resulting in hyperplasia and proliferating cysts. While HK1.ras/fos-Δ5PTEN(flx) papillomatogenesis was accelerated, malignant conversion was delayed and tumours exhibited well-differentiated squamous cell carcinoma (wdSCC) histotypes, suggesting inhibition of early-stage malignant progression. Immediate elevated p53/p21 expression was observed in HK1.ras/fos-Δ5PTEN(flx) hyperplasia, cysts and papillomas, and while malignant conversion required p53 loss, elevated p21 expression persisted in most wdSCCs to limit further progression, unless p21 was also lost and wdSCC progressed to more aggressive carcinomas. In contrast, TPA-promoted (that is, c-fos-activated) bi-genic HK1.ras-Δ5PTEN(flx) cohorts lost p53/p21 expression during early papillomatogenesis and rapidly produced poorly differentiated carcinomas (pdSCCs) with high BrdU-labelling and elevated cyclin D1/E2 expression levels, indicative of a progression mechanism driven by failures in cell-cycle control. Intriguingly, HK1.ras/fos-Δ5PTEN(flx) wdSCCs did not exhibit similar failures, as western and immunofluorescence analysis found downregulated cyclin E2 whenever p21 persisted; further, while westerns detected elevated cyclin D1, immunofluorescence identified reduced expression in proliferative basal layer nuclei and a redistributed expression profile throughout p21-positive wdSCC keratinocytes. These data demonstrate that rapid early epidermal responses to ras(Ha)/fos/ΔPTEN co-operation involve induction of p53/p21 to alter differentiation and divert excessive proliferation into cyst formation. Further, despite three potent oncogenic insults p53 loss was required for malignant conversion, and following p53 loss persistent, p53-independent p21 expression possessed the potency to limit early-stage malignant progression via cyclin D1/E2 inhibition.
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Ciclina D1/antagonistas & inhibidores , Ciclinas/antagonistas & inhibidores , Fosfohidrolasa PTEN/fisiología , Proteínas Proto-Oncogénicas c-fos/fisiología , Proteínas Proto-Oncogénicas p21(ras)/fisiología , Neoplasias Cutáneas/metabolismo , Proteína p53 Supresora de Tumor/fisiología , Animales , Ciclo Celular , Diferenciación Celular , Proliferación Celular , Regulación Neoplásica de la Expresión Génica , Queratinocitos/citología , Ratones , Ratones Transgénicos , Fosfohidrolasa PTEN/genética , Transducción de Señal , Neoplasias Cutáneas/genética , Acetato de Tetradecanoilforbol/químicaRESUMEN
Interpretations of major climatic and biological events in Earth history are, in large part, derived from the stable carbon isotope records of carbonate rocks and sedimentary organic matter. Neoproterozoic carbonate records contain unusual and large negative isotopic anomalies within long periods (10-100 million years) characterized by δ(13)C in carbonate (δ(13)C(carb)) enriched to more than +5 per mil. Classically, δ(13)C(carb) is interpreted as a metric of the relative fraction of carbon buried as organic matter in marine sediments, which can be linked to oxygen accumulation through the stoichiometry of primary production. If a change in the isotopic composition of marine dissolved inorganic carbon is responsible for these excursions, it is expected that records of δ(13)C(carb) and δ(13)C in organic carbon (δ(13)C(org)) will covary, offset by the fractionation imparted by primary production. The documentation of several Neoproterozoic δ(13)C(carb) excursions that are decoupled from δ(13)C(org), however, indicates that other mechanisms may account for these excursions. Here we present δ(13)C data from Mongolia, northwest Canada and Namibia that capture multiple large-amplitude (over 10 per mil) negative carbon isotope anomalies, and use these data in a new quantitative mixing model to examine the behaviour of the Neoproterozoic carbon cycle. We find that carbonate and organic carbon isotope data from Mongolia and Canada are tightly coupled through multiple δ(13)C(carb) excursions, quantitatively ruling out previously suggested alternative explanations, such as diagenesis or the presence and terminal oxidation of a large marine dissolved organic carbon reservoir. Our data from Namibia, which do not record isotopic covariance, can be explained by simple mixing with a detrital flux of organic matter. We thus interpret δ(13)C(carb) anomalies as recording a primary perturbation to the surface carbon cycle. This interpretation requires the revisiting of models linking drastic isotope excursions to deep ocean oxygenation and the opening of environments capable of supporting animals.
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Ciclo del Carbono/fisiología , Animales , Canadá , Isótopos de Carbono/análisis , Sedimentos Geológicos/química , Historia Antigua , Mongolia , Namibia , Océanos y Mares , Agua de Mar/químicaRESUMEN
AIMS: To investigate whether glucose lowering with the selective sodium glucose transporter 2 (SGLT2) inhibitor dapagliflozin would prevent or reduce the decline of pancreatic function and disruption of normal islet morphology. METHODS: Female Zucker diabetic fatty (ZDF) rats, 7-8 weeks old, were placed on high-fat diet. Dapagliflozin (1 mg/kg/day, p.o.) was administered for â¼33 days either from initiation of high-fat diet or when rats were moderately hyperglycaemic. Insulin sensitivity and pancreatic function were evaluated using a hyperglycaemic clamp in anaesthetized animals (n = 5-6); ß-cell function was quantified using the disposition index (DI) to account for insulin resistance compensation. Pancreata from a matched subgroup (n = 7-8) were fixed and ß-cell mass and islet morphology investigated using immunohistochemical methods. RESULTS: Dapagliflozin, administered from initiation of high-fat feeding, reduced the development of hyperglycaemia; after 24 days, blood glucose was 8.6 ± 0.5 vs. 13.3 ± 1.3 mmol/l (p < 0.005 vs. vehicle) and glycated haemoglobin 3.6 ± 0.1 vs. 4.8 ± 0.26% (p < 0.003 vs. vehicle). Dapagliflozin improved insulin sensitivity index: 0.08 ± 0.01 vs. 0.02 ± 0.01 in obese controls (p < 0.03). DI was improved to the level of lean control rats (dapagliflozin 0.29 ± 0.04; obese control 0.15 ± 0.01; lean 0.28 ± 0.01). In dapagliflozin-treated rats, ß-cell mass was less variable and significant improvement in islet morphology was observed compared to vehicle-treated rats, although there was no change in mean ß-cell mass with dapagliflozin. Results were similar when dapagliflozin treatment was initiated when animals were already moderately hyperglycaemic. CONCLUSION: Sustained glucose lowering with dapagliflozin in this model of type 2 diabetes prevented the continued decline in functional adaptation of pancreatic ß-cells.
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Diabetes Mellitus Tipo 2/tratamiento farmacológico , Glucósidos/farmacología , Hiperglucemia/tratamiento farmacológico , Islotes Pancreáticos/citología , Obesidad/tratamiento farmacológico , Páncreas/efectos de los fármacos , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Animales , Compuestos de Bencidrilo , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/fisiopatología , Femenino , Hiperglucemia/fisiopatología , Obesidad/fisiopatología , Páncreas/fisiología , Ratas , Ratas ZuckerRESUMEN
BACKGROUND: Silver-Russell syndrome (SRS) is characterised by intrauterine growth restriction, poor postnatal growth, relative macrocephaly, triangular face and asymmetry. Maternal uniparental disomy (mUPD) of chromosome 7 and hypomethylation of the imprinting control region (ICR) 1 on chromosome 11p15 are found in 5-10% and up to 60% of patients with SRS, respectively. As many features are non-specific, diagnosis of SRS remains difficult. Studies of patients in whom the molecular diagnosis is confirmed therefore provide valuable clinical information on the condition. METHODS: A detailed, prospective study of 64 patients with mUPD7 (n=20) or ICR1 hypomethylation (n=44) was undertaken. RESULTS AND CONCLUSIONS: The considerable overlap in clinical phenotype makes it difficult to distinguish these two molecular subgroups reliably. ICR1 hypomethylation was more likely to be scored as 'classical' SRS. Asymmetry, fifth finger clinodactyly and congenital anomalies were more commonly seen with ICR1 hypomethylation, whereas learning difficulties and referral for speech therapy were more likely with mUPD7. Myoclonus-dystonia has been reported previously in one mUPD7 patient. The authors report mild movement disorders in three further cases. No correlation was found between clinical severity and level of ICR1 hypomethylation. Use of assisted reproductive technology in association with ICR1 hypomethylation seems increased compared with the general population. ICR1 hypomethylation was also observed in affected siblings, although recurrence risk remains low in the majority of cases. Overall, a wide range of severity was observed, particularly with ICR1 hypomethylation. A low threshold for investigation of patients with features suggestive, but not typical, of SRS is therefore recommended.
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Epigénesis Genética , Estudios de Asociación Genética/métodos , Síndrome de Silver-Russell/genética , Adolescente , Adulto , Niño , Preescolar , Cromosomas Humanos Par 11/genética , Cromosomas Humanos Par 7/genética , Metilación de ADN , Femenino , Impresión Genómica , Humanos , Lactante , Masculino , Canales de Potasio con Entrada de Voltaje/genética , Estudios Prospectivos , ARN Largo no Codificante , ARN no Traducido/genética , Síndrome de Silver-Russell/patología , Disomía Uniparental , Adulto JovenAsunto(s)
Carcinoma Medular/patología , Enfermedad de Crohn/patología , Neoplasias del Íleon/patología , Inestabilidad de Microsatélites , Proteínas Adaptadoras Transductoras de Señales/genética , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Biomarcadores de Tumor/análisis , Carcinoma Medular/complicaciones , Carcinoma Medular/genética , Enfermedad de Crohn/complicaciones , Enfermedad de Crohn/genética , Silenciador del Gen , Humanos , Neoplasias del Íleon/complicaciones , Neoplasias del Íleon/genética , Masculino , Persona de Mediana Edad , Homólogo 1 de la Proteína MutL , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismoRESUMEN
OBJECTIVES: QF-PCR analysis can be used as a rapid test to diagnose primary trisomy in prenatal samples. Mosaicism in CVS detected by QF-PCR has previously been reported; however, no case has so far been reported in which the QF-PCR result was completely discrepant to that of the karyotype analysis from a long-term culture. METHODS: A CVS, referred because of a high serum screening risk of 1:10 for Down Syndrome and 1:110 for Edwards Syndrome, was tested by QF-PCR analysis and chromosome analysis of cultured cells. Subsequent analyses were carried out on a follow-up amniotic fluid sample and foetal tissue samples. RESULTS: Conflicting results were obtained between QF-PCR analysis on two independent fronds from the chorionic villi and chromosome analysis on cultured CVS. Cytogenetic and molecular analysis on a subsequent amniotic fluid sample indicated trisomy 18 with no evidence of mosaicism. Analysis of follow-up tissue confirmed trisomy in a foetal skin sample and mosaicism for trisomy 18 in four placental sites tested. CONCLUSION: We report here an apparently normal CVS QF-PCR result that was completely discrepant with the trisomy 18 positive karyotype result on long-term culture. This has important implications regarding our current testing protocol.
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Muestra de la Vellosidad Coriónica/métodos , Trastornos de los Cromosomas/diagnóstico , Cariotipificación/métodos , Reacción en Cadena de la Polimerasa/métodos , Trisomía , Adulto , Técnicas de Cultivo de Célula , Cromosomas Humanos Par 18 , Femenino , Humanos , Hibridación Fluorescente in Situ , Embarazo , Piel/patologíaAsunto(s)
Trastornos de los Cromosomas/diagnóstico , Hibridación Fluorescente in Situ , Reacción en Cadena de la Polimerasa , Diagnóstico Prenatal/métodos , Aberraciones Cromosómicas , Análisis Costo-Beneficio , Femenino , Humanos , Hibridación Fluorescente in Situ/economía , Cariotipificación , Reacción en Cadena de la Polimerasa/economía , Embarazo , Diagnóstico Prenatal/economía , Sensibilidad y EspecificidadAsunto(s)
Síndrome de Angelman/genética , Proteínas Cromosómicas no Histona , Proteínas de Unión al ADN/genética , Niño , Preescolar , Estudios de Cohortes , ADN/química , ADN/genética , Análisis Mutacional de ADN , Discapacidades del Desarrollo/genética , Femenino , Humanos , Lactante , Masculino , Proteína 2 de Unión a Metil-CpG , Mutación , Polimorfismo Conformacional Retorcido-Simple , Proteínas Represoras/genética , Factores de TranscripciónAsunto(s)
Síndrome de Beckwith-Wiedemann/etiología , Técnicas Reproductivas Asistidas/efectos adversos , Síndrome de Beckwith-Wiedemann/genética , Estudios de Cohortes , Femenino , Fertilización In Vitro/efectos adversos , Fertilización In Vitro/estadística & datos numéricos , Impresión Genómica/genética , Humanos , Parto , Técnicas Reproductivas Asistidas/estadística & datos numéricos , Inyecciones de Esperma Intracitoplasmáticas/efectos adversos , Inyecciones de Esperma Intracitoplasmáticas/estadística & datos numéricosRESUMEN
Rett syndrome (RTT) is an X-linked dominant neurological disorder, which appears to be the most common genetic cause of profound combined intellectual and physical disability in Caucasian females. This syndrome has been associated with mutations of the MECP2 gene, a transcriptional repressor of unknown target genes. We report a detailed mutational analysis of a large cohort of RTT patients from the UK and Italy. This study has permitted us to produce a hot spot map of the mutations identified. Bioinformatic analysis of the mutations, taking advantage of structural and evolutionary data, leads us to postulate the existence of a new functional domain in the MeCP2 protein, conserved among brain-specific regulatory factors.
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Proteínas Cromosómicas no Histona , Mapeo Cromosómico , Biología Computacional , Análisis Mutacional de ADN , Proteínas de Unión al ADN/genética , Mutación/genética , Proteínas Represoras , Síndrome de Rett/genética , Adolescente , Adulto , Secuencia de Aminoácidos/genética , Secuencia de Bases/genética , Niño , Preescolar , Proteínas de Unión al ADN/metabolismo , Femenino , Factores de Transcripción Forkhead , Humanos , Lactante , Recién Nacido , Italia , Proteína 2 de Unión a Metil-CpG , Datos de Secuencia Molecular , Proteínas Nucleares/genética , Estructura Terciaria de Proteína/genética , Factores de Transcripción/genética , Reino UnidoRESUMEN
BACKGROUND: Multifaceted programs that combine assessment with interventions have been shown to reduce subsequent falls in some clinical trials. We tested this approach to see whether it would be effective if offered as a consultation service using existing health care resources. METHODS: The subjects of this randomized controlled trial had to be aged 65 years or more and had to have fallen within the previous 3 months. They were randomly assigned to receive either usual care or the intervention, which consisted of in-home assessment in conjunction with the development of an individualized treatment plan, including an exercise program for those deemed likely to benefit. The primary outcomes were the proportion of participants who fell and the rate of falling during the following year. Visits to the emergency department and admissions to hospital were secondary outcomes. RESULTS: One hundred and sixty-three subjects were randomly assigned to either the control or the intervention group, and 152 provided data about their falls. There were no significant differences between the control and intervention groups in the cumulative number of falls (311 v. 241, p = 0.34), having one or more falls (79.2% v. 72.0%, p = 0.30) or in the mean number of falls (4.0 v. 3.2, p = 0.43). Analysis of secondary outcomes (health care use) also showed no significant differences between the intervention group and the control group. In the Cox regression analysis, there was no significant difference between the groups in the proportion of subjects having one or more falls (p = 0.55), but there was a significantly (p < 0.001) longer time between falls in the intervention group. In a post hoc subgroup analysis, subjects with more than 2 falls in the 3 months preceding study entry who had been assigned to the intervention group were less likely to fall (p = 0.046) and had a significantly longer time between falls (p < 0.001), when compared with the group who received usual care. INTERPRETATION: The intervention did not decrease significantly the cumulative number of falls, the likelihood of participants having at least one fall over the next year or the mean number of falls. It did increase significantly the time between falls in a survival analysis when age, sex and history of falling were used as covariates.
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Accidentes por Caídas/prevención & control , Servicios de Salud Comunitaria/organización & administración , Servicios de Salud para Ancianos/organización & administración , Derivación y Consulta , Accidentes por Caídas/estadística & datos numéricos , Anciano , Distribución de Chi-Cuadrado , Femenino , Evaluación Geriátrica , Humanos , Actividades Recreativas , Masculino , Evaluación de Resultado en la Atención de Salud , Modelos de Riesgos Proporcionales , Factores de Riesgo , Estadísticas no Paramétricas , Análisis de SupervivenciaRESUMEN
Although X-linked myotubular myopathy (XLMTM) is a recessive disorder, heterozygous female carriers of MTM1 mutations may present with limb girdle and facial weakness. It is proposed that manifesting heterozygote females with XLMTM have a skewed pattern of X-chromosome inactivation. However, skewed X-chromosome inactivation was not detected in either the lymphocyte or muscle DNA of a woman who presented with limb girdle/facial weakness and was found to be heterozygous for the R224X mutation.
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Tamización de Portadores Genéticos , Ligamiento Genético/genética , Debilidad Muscular/genética , Miopatías Estructurales Congénitas/genética , Proteínas Tirosina Fosfatasas/genética , Cromosoma X/genética , Adulto , Compensación de Dosificación (Genética) , Extremidades/patología , Cara/patología , Femenino , Humanos , Lactante , Masculino , Debilidad Muscular/patología , Músculo Esquelético/patología , Mutación/genética , Miopatías Estructurales Congénitas/patología , Linaje , Proteínas Tirosina Fosfatasas no ReceptorasRESUMEN
Standards for assessing and managing suicide risk were developed and incorporated into a guidance manual for general practitioners. The effects of the manual on opinions and practice were evaluated using a quasi-experimental controlled before/after design, comparing participating general practitioners with others who did not use the manual. Thirty four general practitioners participated over a six-month period. The intervention group showed changes in perceptions, with increased satisfaction with their own methods and in their recognition and assessment of suicide risk. Their practice changed, with increased recording of relevant factors in notes. The comparison group did not change in these ways. It is concluded that general practitioners' practice and opinions in assessing and managing suicide risk were significantly improved using a minimal intervention. Given the importance of the topic and the small size of this study, further research is needed, examining changes in professional practice, knowledge and attitudes.
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Medicina Familiar y Comunitaria/normas , Guías de Práctica Clínica como Asunto , Medición de Riesgo/normas , Suicidio/psicología , Síntomas Afectivos/complicaciones , Síntomas Afectivos/diagnóstico , Competencia Clínica , Depresión/complicaciones , Depresión/diagnóstico , Diagnóstico Diferencial , Humanos , Manuales como Asunto , Auditoría Médica/estadística & datos numéricos , Trastornos Mentales/complicaciones , Trastornos Mentales/diagnóstico , Grupo de Atención al Paciente/normas , Factores de Riesgo , Trastornos Relacionados con Sustancias/complicaciones , Trastornos Relacionados con Sustancias/diagnóstico , Intento de Suicidio , Encuestas y Cuestionarios , Reino Unido , Prevención del SuicidioRESUMEN
Rett syndrome is an X-linked dominant neurological disorder, which appears to be the commonest genetic cause of profound combined intellectual and physical disability in Caucasian females. Recently, this syndrome has been associated with mutations of the MECP2 gene, a transcriptional repressor of still unknown target genes. Here we report a detailed mutational analysis of 62 patients from UK and Italian archives, representing the first comparative study among different populations and one of the largest number of cases so far analyzed. We review the literature on MECP2 mutations in Rett syndrome. This analysis has permitted us to produce a map of the recurrent mutations identified in this and previous studies. Bioinformatic analysis of the mutations, taking advantage of structural and evolutionary data, leads us to postulate the existence of a new functional domain in the MeCP2 protein, which is conserved among brain-specific regulatory factors.