RESUMO
Cerebral white matter pathology is a common CNS manifestation of Fabry disease, visualized as white matter hyperintensities on MRI in 42-81% of patients. Diffusion tensor imaging (DTI) MRI is a sensitive technique to quantify microstructural damage within the white matter with potential value as a disease biomarker. We evaluated the pattern of DTI abnormalities in Fabry disease, and their correlations with cognitive impairment, mood, anxiety, disease severity and plasma lyso-Gb3 levels in 31 patients with genetically proven Fabry disease and 19 age-matched healthy control subjects. We obtained average values of fractional anisotropy and mean diffusivity within the white matter and performed voxelwise analysis with tract-based spatial statistics. Using a standardized neuropsychological test battery, we assessed processing speed, executive function, anxiety, depression and disease severity. The mean age (% male) was 44.1 (45%) for patients with Fabry disease and 37.4 (53%) for the healthy control group. In patients with Fabry disease, compared to healthy controls the mean average white matter fractional anisotropy was lower in [0.423 (standard deviation, SD 0.023) versus 0.446 (SD 0.016), P = 0.002] while mean average white matter mean diffusivity was higher (749 × 10-6 mm2/s (SD 32 × 10-6) versus 720 × 10-6 mm2/s (SD 21 × 10-6), P = 0.004]. Voxelwise statistics showed that the diffusion abnormalities for both fractional anisotropy and mean diffusivity were anatomically widespread. A lesion probability map showed that white matter hyperintensities also had a wide anatomical distribution with a predilection for the posterior centrum semiovale. However, diffusion abnormalities in Fabry disease were not restricted to lesional tissue; compared to healthy controls, the normal appearing white matter in patients with Fabry disease had reduced fractional anisotropy [0.422 (SD 0.022) versus 0.443 (SD 0.017) P = 0.003] and increased mean diffusivity [747 × 10-6 mm2/s (SD 26 × 10-6) versus 723 × 10-6 mm2/s (SD 22 × 10-6), P = 0.008]. Within patients, average white matter fractional anisotropy and white matter lesion volume showed statistically significant correlations with Digit Symbol Coding Test score (r = 0.558, P = 0.001; and r = -0.633, P ≤ 0.001, respectively). Average white matter fractional anisotropy correlated with the overall Mainz Severity Score Index (r = -0.661, P ≤ 0.001), while average white matter mean diffusivity showed a strong correlation with plasma lyso-Gb3 levels (r = 0.559, P = 0.001). Our findings using DTI confirm widespread areas of microstructural white matter disruption in Fabry disease, extending beyond white matter hyperintensities seen on conventional MRI. Moreover, diffusion measures show strong correlations with cognition (processing speed), clinical disease severity and a putative plasma biomarker of disease activity, making them promising quantitative biomarkers for monitoring Fabry disease severity and progression.
Assuntos
Doença de Fabry/diagnóstico por imagem , Doença de Fabry/psicologia , Substância Branca/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Ansiedade/etiologia , Ansiedade/psicologia , Encéfalo/diagnóstico por imagem , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/psicologia , Depressão/etiologia , Depressão/psicologia , Imagem de Tensor de Difusão , Função Executiva , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos do Humor/etiologia , Transtornos do Humor/psicologia , Testes Neuropsicológicos , Triexosilceramidas/sangue , Adulto JovemRESUMO
In June 2017, an outbreak of Salmonella Kottbus infection was suspected in Germany. We investigated the outbreak with whole-genome sequencing (WGS) and a case-control study. Forty-six isolates from 69 cases were subtyped. Three WGS clusters were identified: cluster 1 (n = 36), cluster 2 (n = 5) and cluster 3 (n = 3). Compared to controls, cluster 1 cases more frequently consumed raw smoked ham (odds ratio (OR) 10, 95% confidence interval (CI) 1.2-88) bought at supermarket chain X (OR 36, 95% CI 4-356; 9/10 consumed ham Y). All four cluster 2 cases interviewed had consumed quail eggs. Timely WGS was invaluable in distinguishing concurrent outbreaks of a rare Salmonella serotype.
Assuntos
Surtos de Doenças , Doenças Transmitidas por Alimentos/epidemiologia , Epidemiologia Molecular/métodos , Tipagem Molecular/métodos , Infecções por Salmonella/epidemiologia , Salmonella enterica/classificação , Sequenciamento Completo do Genoma/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Análise por Conglomerados , Comportamento Alimentar , Feminino , Doenças Transmitidas por Alimentos/microbiologia , Alemanha/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Infecções por Salmonella/microbiologia , Salmonella enterica/genética , Salmonella enterica/isolamento & purificaçãoRESUMO
INTRODUCTION: X-linked hypophosphatemia (XLH) is a rare, lifelong, progressive disease characterised by renal phosphate wasting and abnormal bone mineralisation. Symptoms begin in early childhood, with the development of rickets and related skeletal deformities and reduced growth, progressing to long-term complications, including pseudofractures and fractures, as well as pain, stiffness and fatigue. The present study was designed to explore the patient experience of pain, stiffness and fatigue and the psychosocial impact of XLH in detail. METHODS: A cross-sectional qualitative study was conducted in the United Kingdom (18), Finland (6), France (4), Germany (1) and Luxembourg (1) with XLH patients aged 26 and over. Interview discussion guides were developed in consultation with clinical experts and patient associations. Data were analysed thematically. RESULTS: Participants (N = 30) described pain, stiffness and fatigue as frequently experienced symptoms with a significant impact on physical functioning and activities of daily living (ADLs). Some also described the symptoms as impacting their mood/mental health, relationships, social life and leisure activities. Participants described how common symptoms could interact or aggravate other symptoms. Symptoms had often worsened over time, and for many, were associated with concern about the future. Most participants were worried or felt guilty about having children with XLH. The findings confirmed and extended the existing model of the burden of XLH. CONCLUSION: The present study is the first to provide an in-depth analysis of pain, stiffness and fatigue, their impact and the interrelatedness of these symptoms among adults with XLH. The study also described the psychosocial impact of XLH as a hereditary, lifelong progressive disease.
Assuntos
Atividades Cotidianas/psicologia , Raquitismo Hipofosfatêmico Familiar/psicologia , Dor/psicologia , Qualidade de Vida/psicologia , Adulto , Idoso , Estudos Transversais , Europa (Continente) , Raquitismo Hipofosfatêmico Familiar/diagnóstico , Raquitismo Hipofosfatêmico Familiar/terapia , Fadiga/psicologia , Feminino , Finlândia , Fraturas Ósseas/psicologia , França , Alemanha , Humanos , Masculino , Pessoa de Meia-Idade , Pesquisa Qualitativa , Reino UnidoRESUMO
BACKGROUND AND PURPOSE: Pompe disease is a rare inheritable muscle disorder for which enzyme replacement therapy (ERT) has been available since 2006. Uniform criteria for starting and stopping ERT in adult patients were developed and reported here. METHODS: Three consensus meetings were organized through the European Pompe Consortium, a network of experts from 11 European countries in the field of Pompe disease. A systematic review of the literature was undertaken to determine the effectiveness of ERT in adult patients on a range of clinical outcome measures and quality of life. A narrative synthesis is presented. RESULTS: Consensus was reached on how the diagnosis of Pompe disease should be confirmed, when treatment should be started, reasons for stopping treatment and the use of ERT during pregnancy. This was based on expert opinion and supported by the literature. One clinical trial and 43 observational studies, covering a total of 586 individual adult patients, provided evidence of a beneficial effect of ERT at group level. At individual patient level, the response to treatment varied, but factors associated with a patient's response to ERT were not described in many studies. Eleven observational studies focused on more severely affected patients, suggesting that ERT can also be beneficial in these patients. There are no studies on the effects of ERT in pre-symptomatic patients. CONCLUSIONS: This is the first European consensus recommendation for starting and stopping ERT in adult patients with Pompe disease, based on the extensive experience of experts from different countries.
Assuntos
Terapia de Reposição de Enzimas , Doença de Depósito de Glicogênio Tipo II/tratamento farmacológico , Qualidade de Vida , Adulto , Consenso , Esquema de Medicação , Europa (Continente) , Humanos , Guias de Prática Clínica como AssuntoRESUMO
OBJECTIVES: To determine the effectiveness of enzyme replacement therapy (ERT) for adults with late-onset Pompe disease. DESIGN: A longitudinal cohort study including prospective and retrospective clinical outcome data. Age- and gender-adjusted treatment effects were estimated using generalised linear mixed models. Treated patients contributed data before and during treatment. Untreated patients contributed natural history data. PARTICIPANTS: Consenting adults (N = 62) with a diagnosis of late-onset Pompe disease who attended a specialist treatment centre in England. This cohort represented 83 % of all patients in the UK with a confirmed diagnosis of this rare condition. At study entry, all but three patients were receiving ERT (range of treatment duration, 0 to 3.1 years). OUTCOME MEASURES: Percent predicted forced vital capacity (%FVC); ventilation dependency; mobility; 6 min walk test (6MWT); muscle strength and body mass index (BMI). RESULTS: An association was found between time on ERT and significant increases in the distance walked in the 6MWT (p < 0.001) and muscle strength scores (p < 0.001). Improvements in both these measures were seen over the first 2 years of treatment with ERT. No statistically significant relationship was found between time on ERT and respiratory function or in BMI. CONCLUSIONS: These data provide some further evidence of the effectiveness of ERT in adults with late-onset Pompe disease. SYNOPSIS: The results of this longitudinal cohort study of 62 adults with late-onset Pompe disease, provide further evidence on the effectiveness of ERT in this rare condition.
Assuntos
Terapia de Reposição de Enzimas/métodos , Doença de Depósito de Glicogênio Tipo II/tratamento farmacológico , Adolescente , Adulto , Idade de Início , Idoso , Índice de Massa Corporal , Inglaterra , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Força Muscular , Estudos Prospectivos , Estudos Retrospectivos , Resultado do Tratamento , Caminhada , Adulto JovemRESUMO
BACKGROUND: Within Europe, the management of pyridoxine (B6) non-responsive homocystinuria (HCU) may vary but there is limited knowledge about treatment practice. AIM: A comparison of dietetic management practices of patients with B6 non-responsive HCU in European centres. METHODS: A cross-sectional audit by questionnaire was completed by 29 inherited metabolic disorder (IMD) centres: (14 UK, 5 Germany, 3 Netherlands, 2 Switzerland, 2 Portugal, 1 France, 1 Norway, 1 Belgium). RESULTS: 181 patients (73% >16 years of age) with HCU were identified. The majority (66%; n=119) were on dietary treatment (1-10 years, 90%; 11-16 years, 82%; and >16 years, 58%) with or without betaine and 34% (n=62) were on betaine alone. The median natural protein intake (g/day) on diet only was, by age: 1-10 years, 12 g; 11-16 years, 11 g; and >16 years, 45 g. With diet and betaine, median natural protein intake (g/day) by age was: 1-10 years, 13 g; 11-16 years, 20 g; and >16 years, 38 g. Fifty-two percent (n=15) of centres allocated natural protein by calculating methionine rather than a protein exchange system. A methionine-free l-amino acid supplement was prescribed for 86% of diet treated patients. Fifty-two percent of centres recommended cystine supplements for low plasma concentrations. Target treatment concentrations for homocystine/homocysteine (free/total) and frequency of biochemical monitoring varied. CONCLUSION: In B6 non-responsive HCU the prescription of dietary restriction by IMD centres declined with age, potentially associated with poor adherence in older patients. Inconsistencies in biochemical monitoring and treatment indicate the need for international consensus guidelines.
Assuntos
Dieta com Restrição de Proteínas , Homocistinúria/dietoterapia , Piridoxina/metabolismo , Adolescente , Adulto , Betaína/administração & dosagem , Criança , Pré-Escolar , Europa (Continente) , Feminino , Homocisteína/sangue , Homocistinúria/sangue , Homocistinúria/epidemiologia , Homocistinúria/patologia , Humanos , Lactente , Masculino , Metionina/metabolismo , Inquéritos e Questionários , Resultado do TratamentoRESUMO
BACKGROUND: To quantify the costs and consequences of managing phenylketonuria (PKU) in the UK and to estimate the potential implications to the UK's National Health Service (NHS) of keeping patients on a phenylalanine-restricted diet for life. METHOD: A computer-based model was constructed depicting the management of PKU patients over the first 36 years of their life, derived from patients suffering from this metabolic disorder in The Health Improvement Network database (a nationally representative database of patients registered with general practitioners in the UK). The model was used to estimate the incidence of co-morbidities and the levels of healthcare resource use and corresponding costs over the 36 years. RESULTS: Patients who remained on a phenylalanine-restricted diet accounted for 38% of the cohort. Forty-seven per cent of patients discontinued their phenylalanine-restricted diet between 15 and 25 years of age. Of these, 73% remained off diet and 27% restarted a restricted diet at a mean 30 years of age. Fifteen per cent of the cohort had untreated PKU. Eleven per cent of patients who remained on a phenylalanine-restricted diet for 36 years received the optimum amount of prescribed amino acid supplements. Patients had a mean 12 general practitioner visits per year and one hospital outpatient visit annually, but phenylalanine levels were only measured once every 18 to 24 months. The mean NHS cost (at 2007/08 prices) of managing a PKU sufferer over the first 36 years of their life was estimated to range between £21 000 and £149 000, depending on the amount of prescribed nutrition they received. CONCLUSION: The findings suggest that the majority of patients with PKU were under-treated. The NHS cost of patient management should not be an obstacle to encouraging patients to remain on a restricted diet until further information becomes available about the long-term clinical impact of stopping such a diet. Nevertheless, patients require counselling and managed follow up regardless of the choices they make about their diet.
Assuntos
Custos de Cuidados de Saúde/estatística & dados numéricos , Modelos Econométricos , Cooperação do Paciente/estatística & dados numéricos , Fenilcetonúrias/dietoterapia , Fenilcetonúrias/economia , Adolescente , Adulto , Orçamentos/estatística & dados numéricos , Comorbidade , Análise Custo-Benefício , Feminino , Recursos em Saúde/economia , Recursos em Saúde/estatística & dados numéricos , Humanos , Incidência , Masculino , Avaliação de Resultados em Cuidados de Saúde , Fenilalanina , Fenilcetonúrias/epidemiologia , Estudos Retrospectivos , Medicina Estatal/economia , Reino Unido/epidemiologiaRESUMO
Pulmonary oedema is a hallmark of acute lung injury (ALI), consisting of various degrees of water and proteins. Physiologically, sodium enters through apical sodium channels (ENaC) and is extruded basolaterally by a sodium-potassium-adenosine-triphosphatase pump (Na(+) /K(+) -ATPase). Water follows to maintain iso-osmolar conditions and to keep alveoli dry. We postulated that the volatile anaesthetic sevoflurane would impact oedema resolution positively in an in-vitro and in-vivo model of ALI. Alveolar epithelial type II cells (AECII) and mixed alveolar epithelial cells (mAEC) were stimulated with 20 µg/ml lipopolysaccharide (LPS) and co-exposed to sevoflurane for 8 h. In-vitro active sodium transport via ENaC and Na(+) /K(+) -ATPase was determined, assessing (22) sodium and (86) rubidium influx, respectively. Intratracheally applied LPS (150 µg) was used for the ALI in rats under sevoflurane or propofol anaesthesia (8 h). Oxygenation index (PaO(2) /FiO(2) ) was calculated and lung oedema assessed determining lung wet/dry ratio. In AECII LPS decreased activity of ENaC and Na(+) /K(+) -ATPase by 17·4% ± 13·3% standard deviation and 16·2% ± 13·1%, respectively. These effects were reversible in the presence of sevoflurane. Significant better oxygenation was observed with an increase of PaO(2) /FiO(2) from 189 ± 142 mmHg to 454 ± 25 mmHg after 8 h in the sevoflurane/LPS compared to the propofol/LPS group. The wet/dry ratio in sevoflurane/LPS was reduced by 21·6% ± 2·3% in comparison to propofol/LPS-treated animals. Sevoflurane has a stimulating effect on ENaC and Na(+) /K(+) -ATPase in vitro in LPS-injured AECII. In-vivo experiments, however, give strong evidence that sevoflurane does not affect water reabsorption and oedema resolution, but possibly oedema formation.
Assuntos
Lesão Pulmonar Aguda/patologia , Pulmão/patologia , Éteres Metílicos/farmacologia , Alvéolos Pulmonares/metabolismo , Edema Pulmonar/patologia , Lesão Pulmonar Aguda/tratamento farmacológico , Anestésicos/farmacologia , Animais , Transporte Biológico Ativo/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Lipopolissacarídeos/farmacologia , Pulmão/efeitos dos fármacos , Masculino , Oxigênio/análise , Alvéolos Pulmonares/efeitos dos fármacos , Edema Pulmonar/metabolismo , Ratos , Ratos Wistar , Síndrome do Desconforto Respiratório/metabolismo , Rubídio/metabolismo , Sevoflurano , Sódio/metabolismo , Canais de Sódio/efeitos dos fármacos , Isótopos de Sódio/metabolismo , ATPase Trocadora de Sódio-Potássio/metabolismoRESUMO
OBJECTIVES: To investigate the posterior fossa of normal fetuses and fetuses with open spina bifida in stored three-dimensional (3D) volumes and to describe signs that might allow early detection of this defect. METHODS: A prospective study of 3D volumes of the fetal brain obtained from 10 normal fetuses and three fetuses with open spina bifida was undertaken. Measurements of the anteroposterior diameters of the cisterna magna and fourth ventricle were taken in the tilted axial view. In the mid-sagittal plane the brainstem (BS) diameter and the brainstem-occipital bone (BSOB) distance were measured. The BS/BSOB ratio was calculated. All measurements were expressed as Z-scores. Structural analysis of the differences in the posterior fossa between normal fetuses and fetuses with open spina bifida was undertaken. RESULTS: In normal fetuses all measurements were within ±2.5 Z-scores. In three fetuses with open spina bifida the BS Z-scores were 2.7, 2.8 and 2.8; the BSOB scores were -3.4, -2.8 and -2.9; the cisterna magna scores were -5.6, -3.7 and -4.2; and the BS/BSOB ratio scores were 4.1, 9.7 and 8.9. In normal fetuses the cisterna magna was posterior to the fourth ventricle and extended along its entire length. In fetuses with open spina bifida the cisterna magna was partially or completely obliterated. CONCLUSIONS: Assessment of the cranial posterior fossa is feasible at 11-13 weeks' gestation. There are distinct signs in fetuses with open spina bifida which can be evaluated by ultrasonography.
Assuntos
Cisterna Magna/diagnóstico por imagem , Fossa Craniana Posterior/diagnóstico por imagem , Quarto Ventrículo/diagnóstico por imagem , Imageamento Tridimensional , Espinha Bífida Cística/diagnóstico por imagem , Ultrassonografia Pré-Natal/métodos , Abdome , Tronco Encefálico/diagnóstico por imagem , Cisterna Magna/embriologia , Fossa Craniana Posterior/anormalidades , Fossa Craniana Posterior/embriologia , Estudos de Viabilidade , Feminino , Quarto Ventrículo/embriologia , Idade Gestacional , Humanos , Osso Occipital/diagnóstico por imagem , Gravidez , Estudos Prospectivos , Espinha Bífida Cística/embriologiaRESUMO
INTRODUCTION: Fabry disease (FD) is an X-linked lysosomal storage disorder resulting in vascular glycosphingolipid accumulation and increased stroke risk. MRI findings associated with FD include white matter hyperintensities (WMH) and cerebral microbleeds (CMBs), suggesting the presence of cerebral small vessel disease. MRI-visible perivascular spaces (PVS) are another promising marker of small vessel disease associated with impaired interstitial fluid drainage. We investigated the association of PVS severity and anatomical distribution with FD. PATIENTS AND METHODS: We compared patients with genetically proven FD to healthy controls. PVS, WMH, lacunes and CMBs were rated on standardised sequences using validated criteria and scales, blinded to diagnosis. A trained observer (using a validated rating scale), quantified the total severity of PVS. We used logistic regression to investigate the association of severe PVS with FD. RESULTS: We included 33 FD patients (median age 44, 44.1% male) and 20 healthy controls (median age 33.5, 50% male). Adjusting for age and sex, FD was associated with more severe basal ganglia PVS (odds ratio (OR) 5.80, 95% CI 1.03-32.7) and higher total PVS score (OR 4.03, 95% CI 1.36-11.89). Compared with controls, participants with FD had: higher WMH volume (median 495.03 mm3 vs 0, p = 0.0008), more CMBs (21.21% vs none, p = 0.04), and a higher prevalence of lacunes (21.21% vs. 5%, p = 0.23). CONCLUSIONS: PVS scores are more severe in FD than control subjects. Our findings have potential relevance for FD diagnosis and suggest that impaired interstitial fluid drainage might be a mechanism of white matter injury in FD.
Assuntos
Doenças de Pequenos Vasos Cerebrais , Doença de Fabry , Acidente Vascular Cerebral , Substância Branca , Adulto , Biomarcadores , Doença de Fabry/diagnóstico por imagem , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Substância Branca/diagnóstico por imagemRESUMO
Weight loss and gastrointestinal disturbances are often seen during miglustat therapy for lysosomal storage diseases. A retrospective analysis of data from a mixed group of patients treated with miglustat at two UK centres was performed to evaluate the effect of two different dietary interventions on body weight and gastrointestinal tolerability during the initial 6 months of miglustat therapy. Neurological outcomes in these patients are not discussed herein. Data were analysed from a total of 29 patients with varied neurolipidoses (21 children/adolescents; 8 adults). Negative mean changes in body weight were seen in children/adolescents on an unmodified diet (-8.1%), and in adults (-4.1%) and children/adolescents (-5.2%) on a low-lactose diet. Patients on the low-disaccharide diet showed a positive mean change in body weight (+2.0%), although there was high variability in this group. Non-parametric sub-analysis of median body-weight change in children/adolescents also showed high variability both within and between diet groups, with no statistically significant difference between the effects of different diets on body weight (p = 0.062). The low-lactose diet reduced gastrointestinal disturbances; single small doses of loperamide were required in some patients. Patients on the low-disaccharide diet showed the lowest frequency of gastrointestinal effects. In conclusion, simple dietary modifications allowed the maintenance of body-weight gain in line with normal growth potential during miglustat therapy in young patients with lysosomal storage diseases, and reduced gastrointestinal disturbances.
Assuntos
1-Desoxinojirimicina/análogos & derivados , Dieta com Restrição de Carboidratos , Inibidores Enzimáticos/uso terapêutico , Glucosiltransferases/antagonistas & inibidores , Lactose/administração & dosagem , Doenças por Armazenamento dos Lisossomos do Sistema Nervoso/tratamento farmacológico , 1-Desoxinojirimicina/efeitos adversos , 1-Desoxinojirimicina/uso terapêutico , Adolescente , Desenvolvimento do Adolescente/efeitos dos fármacos , Adulto , Fatores Etários , Criança , Desenvolvimento Infantil/efeitos dos fármacos , Inglaterra , Inibidores Enzimáticos/efeitos adversos , Gastroenteropatias/induzido quimicamente , Gastroenteropatias/prevenção & controle , Glucosiltransferases/metabolismo , Humanos , Doenças por Armazenamento dos Lisossomos do Sistema Nervoso/diagnóstico , Doenças por Armazenamento dos Lisossomos do Sistema Nervoso/enzimologia , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Redução de Peso/efeitos dos fármacos , Adulto JovemRESUMO
OBJECTIVE: To estimate intersonographer and intrasonographer variance components of fetal nuchal translucency (NT) thickness measurement using the traditional manual approach and a new semi-automated system. METHODS: A semi-automated method was developed for measurement of the NT. In this method, the operator places an adjustable box over the relevant area at the back of the fetal neck. The system draws a line through the center of the nuchal membrane and another line at the edge of the soft tissue overlying the cervical spine. The system then identifies the largest vertical distance between the two lines. The images of 12 fetuses at 11-13 weeks of gestation satisfying the guidelines of The Fetal Medicine Foundation for measurement of NT were selected. They were exported in DICOM format from the ultrasound system, and four versions of each image were stored under different names. The resulting 48 images were presented in random order for electronic assessment. A total of 20 sonographers measured the NT in each set of 48 pictures, twice using the semi-automated system and twice using the manual system, according to a randomized block design. Within- and between-operator variance components were estimated. Relative biases were assessed by comparing the means from the two methods. RESULTS: The estimated between-operator SD using the semi-automated method was 0.0149 mm compared with 0.109 mm for the manual method. The respective within-operator SD values were 0.05 mm and 0.126 mm. The intraclass correlation coefficients for different sonographers measuring the same images were 0.98 and 0.85 for the semi-automated method and the manual method, respectively. CONCLUSION: The measurement of fetal NT is more reliable when a semi-automatic approach is used rather than the traditional manual method.
Assuntos
Diagnóstico por Computador/métodos , Síndrome de Down/diagnóstico por imagem , Medição da Translucência Nucal/métodos , Adulto , Feminino , Humanos , Variações Dependentes do Observador , Gravidez , Primeiro Trimestre da Gravidez , Reprodutibilidade dos TestesRESUMO
OBJECTIVE: To determine whether in fetuses with open spina bifida at 11-13 weeks' gestation the frontomaxillary facial angle is decreased. METHODS: The frontomaxillary facial angle was measured in 20 fetuses with open spina bifida and in 100 normal controls matched for crown-rump length (CRL) at 11 + 0 to 13 + 6 weeks and the values in the two groups were compared. RESULTS: In the control group the frontomaxillary facial angle decreased significantly with CRL from a mean of 84.0 degrees at a CRL of 45 mm to 76.5 degrees at a CRL of 84 mm (SD, 3.26 degrees). In the spina bifida group the mean frontomaxillary facial angle, corrected for CRL, was 9.9 degrees lower than in the controls and it was below the 5(th) centile in 18 (90%) of the cases (P < 0.0001). CONCLUSIONS: In fetuses with open spina bifida at 11-13 weeks' gestation the frontomaxillary facial angle is decreased and this measurement may be useful in early screening for this abnormality.
Assuntos
Face/diagnóstico por imagem , Testa/diagnóstico por imagem , Maxila/diagnóstico por imagem , Disrafismo Espinal/diagnóstico por imagem , Aborto Induzido/estatística & dados numéricos , Estudos de Casos e Controles , Estatura Cabeça-Cóccix , Face/anormalidades , Face/embriologia , Feminino , Testa/anormalidades , Testa/embriologia , Idade Gestacional , Humanos , Região Lombossacral/diagnóstico por imagem , Maxila/anormalidades , Maxila/embriologia , Gravidez , Primeiro Trimestre da Gravidez , Disrafismo Espinal/embriologia , Ultrassonografia Pré-NatalRESUMO
OBJECTIVE: To examine the performance of screening for pre-eclampsia (PE) and gestational hypertension (GH) by a combination of maternal factors and various biophysical and biochemical markers at 11-13 weeks' gestation. METHODS: This was a case-control study of 26 cases of early PE, 90 of late PE, 85 of GH and 201 unaffected controls. Maternal history was recorded, the uterine artery with the lowest pulsatility index (L-PI) and mean arterial pressure (MAP) were measured and stored plasma and serum were analyzed for placental growth factor (PlGF), inhibin-A, activin-A, tumor necrosis factor receptor-1, matrix metalloproteinase-9, pentraxin-3 and P-selectin. RESULTS: Multivariate logistic regression analysis demonstrated that significant prediction for early PE was provided by maternal factors, MAP, uterine artery L-PI and serum PlGF. Significant prediction of late PE was provided by maternal factors, MAP, uterine artery L-PI, PlGF, activin-A and P-selectin. For GH significant prediction was provided by maternal factors, MAP, uterine artery L-PI and activin-A. In screening by a combination of maternal factors, biophysical and biochemical markers the estimated detection rates, at a 5% false-positive rate, were 88.5% (95% CI, 69.8-97.4%) for early PE, 46.7% (95% CI, 36.1-57.5%) for late PE and 35.3% (95% CI, 25.2-46.4%) for GH. CONCLUSION: Combined biophysical and biochemical testing at 11-13 weeks could effectively identify women at high risk for subsequent development of hypertensive disorders in pregnancy.
Assuntos
Pré-Eclâmpsia/sangue , Proteína Plasmática A Associada à Gravidez/análise , Fluxo Pulsátil/fisiologia , Artéria Uterina/fisiopatologia , Adulto , Biomarcadores/sangue , Estudos de Casos e Controles , Reações Falso-Positivas , Feminino , Idade Gestacional , Humanos , Programas de Rastreamento/métodos , Pré-Eclâmpsia/diagnóstico por imagem , Gravidez , Primeiro Trimestre da Gravidez/sangue , Ultrassonografia Doppler , Artéria Uterina/diagnóstico por imagemRESUMO
The extremely rare syndrome including absent pulmonary valve associated with membranous tricuspid atresia or severe tricuspid stenosis, intact ventricular septum and patent ductus arteriosus has been reported sporadically in the postnatal literature. This cardiac defect is characterized by right ventricular dysplasia with asymmetrical ventricular septal hypertrophy, ventricular septum bulging into the left ventricle, small right ventricular cavity, membranous tricuspid atresia or severe stenosis with abnormal papillary muscles and leaflets and absence of the pulmonary valve leaflets. The only prenatal case reported so far was diagnosed at 33 weeks of gestation and terminated shortly thereafter; the natural history of prenatally diagnosed cases is therefore unknown. We report on the intrauterine course of a case diagnosed at 17 weeks of gestation that had a favorable postnatal outcome after palliation.
Assuntos
Coração Fetal/diagnóstico por imagem , Comunicação Interventricular/diagnóstico por imagem , Valva Pulmonar/anormalidades , Atresia Tricúspide/diagnóstico por imagem , Adulto , Aneurisma/diagnóstico por imagem , Aneurisma/embriologia , Aneurisma/cirurgia , Feminino , Comunicação Interventricular/embriologia , Comunicação Interventricular/cirurgia , Humanos , Recém-Nascido , Masculino , Gravidez , Resultado da Gravidez , Artéria Pulmonar/diagnóstico por imagem , Artéria Pulmonar/embriologia , Artéria Pulmonar/cirurgia , Valva Pulmonar/embriologia , Atresia Tricúspide/embriologia , Atresia Tricúspide/patologia , Ultrassonografia Pré-NatalRESUMO
OBJECTIVE: To evaluate the intrauterine course and outcome of tricuspid atresia detected in the fetus. METHODS: This was a retrospective review of all confirmed cases of tricuspid atresia detected prenatally between 1998 and 2006 in three tertiary referral centers in Germany. RESULTS: Fifty-four cases of tricuspid atresia were detected prenatally during the study period and confirmed postnatally: 28 (51.9%) cases had a concordant ventriculoarterial connection of which 14 also had pulmonary outflow obstruction; 25 (46.3%) cases had a discordant ventriculoarterial connection of which 14 also had aortic outflow obstruction, six had pulmonary outflow tract obstruction and two had other associated intracardiac anomalies; and one (1.9%) had a common arterial trunk. The peak velocity index for veins in the ductus venosus was significantly elevated in 19 of the 37 (51.4%) cases assessed; however, this finding did not correlate with adverse intrauterine outcome. There were associated extracardiac anomalies in 12 cases: five with chromosomal anomalies, two with VACTERL association, one with unilateral renal agenesis, one with hypospadia, one with hydrothorax, one with megacystis and one with agenesis of the ductus venosus. Seventeen of the 54 (31.5%) cases underwent termination of pregnancy, two (3.7%) died in utero, two (3.7%) died in infancy and 33 (61.1%) children survived with a median follow-up of 26 (range, 12-120) months. Prenatal echocardiography correctly anticipated the postnatal course and the need for neonatal intervention in 29/35 (82.9%) continued pregnancies; in the remaining six (17.1%) cases the right outflow tract obstruction had been underestimated. CONCLUSIONS: Tricuspid atresia and the frequently associated intracardiac anomalies can be diagnosed in the fetus with considerable accuracy. A thorough search for extracardiac malformations should be performed in order to rule out chromosomal anomalies and multiple malformation syndromes. Elevated pulsatility in the ductus venosus does not indicate cardiac failure. The short-term overall survival in continued pregnancies in our study exceeded 89%, with the greatest rate of loss being in the first year of postnatal life.
Assuntos
Anormalidades Múltiplas/diagnóstico por imagem , Doenças Fetais/diagnóstico por imagem , Coração Fetal/diagnóstico por imagem , Atresia Tricúspide/diagnóstico por imagem , Anormalidades Múltiplas/genética , Anormalidades Múltiplas/mortalidade , Aborto Induzido , Feminino , Doenças Fetais/epidemiologia , Doenças Fetais/genética , Alemanha/epidemiologia , Idade Gestacional , Humanos , Recém-Nascido , Masculino , Gravidez , Resultado da Gravidez , Estudos Retrospectivos , Atresia Tricúspide/genética , Atresia Tricúspide/mortalidade , Ultrassonografia Pré-NatalAssuntos
Doenças Desmielinizantes Hereditárias do Sistema Nervoso Central/diagnóstico , Adrenoleucodistrofia/diagnóstico , Adrenoleucodistrofia/patologia , Adulto , Idade de Início , Biópsia , Encéfalo/patologia , CADASIL/diagnóstico , CADASIL/patologia , Diagnóstico Diferencial , Doenças Desmielinizantes Hereditárias do Sistema Nervoso Central/patologia , Humanos , Leucodistrofia de Células Globoides/diagnóstico , Leucodistrofia de Células Globoides/patologia , Leucodistrofia Metacromática/diagnóstico , Leucodistrofia Metacromática/patologia , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Neuroimagem , Xantomatose Cerebrotendinosa/diagnóstico , Xantomatose Cerebrotendinosa/patologiaRESUMO
BACKGROUND: With improvements in the treatment of children with organic acidaemias (OA), the number surviving to adulthood is increasing. To plan appropriate services for their care it is important to know what their needs are. OBJECTIVE: To describe the clinical and social problems affecting adult patients with OA. PATIENTS AND METHODS: We reviewed the medical records of 15 adult patients diagnosed with OA. Social attainment (housing, schooling and occupation) was analysed. Nutritional status was evaluated by body mass index (BMI) and laboratory studies. Neurological and visceral complications were noted. Cognitive outcome was evaluated by psychometric testing and/or educational attainment. RESULTS: Seven had methylmalonic acidaemia (MMA), 4 isovaleric acidaemia (IVA) and 4 propionic acidaemia (PA). Ten were female, and median age was 23.5 years (range 18-48). All but three had late-onset disease. Two patients became pregnant during follow up. Four patients had obtained university degrees and were working. Three-quarters of the patients required some kind of social support. All had a good nutritional status. Height was normal in IVA and 3 PA patients. Osteoporosis was present in 2 out of 8 patients assessed. A variety of neurocognitive or visceral complications were seen in two-thirds of the patients. Metabolic decompensations were unusual. CONCLUSIONS: The approach to adult patients with OA has to be multidisciplinary, with the clinician and dietician as the core of the team, but with the collaboration of clinical nurses specialists, social workers and other specialist services and the support of a biochemical and molecular laboratory.
Assuntos
Erros Inatos do Metabolismo dos Aminoácidos/diagnóstico , Erros Inatos do Metabolismo dos Aminoácidos/terapia , Necessidades e Demandas de Serviços de Saúde , Adolescente , Adulto , Idade de Início , Erros Inatos do Metabolismo dos Aminoácidos/sangue , Erros Inatos do Metabolismo dos Aminoácidos/epidemiologia , Pré-Escolar , Estudos de Coortes , Feminino , Necessidades e Demandas de Serviços de Saúde/estatística & dados numéricos , Humanos , Lactente , Assistência de Longa Duração , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemRESUMO
Multi-colour flow cytometry is the only technological platform that can analyse the highly complex cellular composition of the immune system in parallel and at a single cell resolution. Analysis of the T cell compartment, in particular, requires the simultaneous measurement of multiple markers in order to account for lineage, phenotype and function. Flow cytometry also enables the analysis of intracellular signalling events. By combining the expression of surface markers, intracellular cytokines, phosphorylated versus unphosphorylated kinases, cell proliferation and DNA profile, mechanistic and kinetic information of subset-specific signalling may be obtained: this has not previously been achieved. Here we present a protocol which permits all of these aspects to be explored simultaneously. By comparing basic procedures previously described we were able to optimise different variables, including the choice of antibody/fluorochrome pairs, permeabilisation, fixation and labelling time, to obtain the best DNA staining of different cell types. We applied this method to study subset-specific signalling related to cytokine production and DNA synthesis in T cells responding to specific antigens.