RESUMO
The role of probiotics as adjunctive measures in the prevention of Clostridium difficile infection (CDI) has been controversial. However, a growing body of evidence has suggested that they have a role in primary prevention of CDI. Elements of this controversy are reviewed and the proposed mechanisms of action, the value and cost effectiveness of probiotics are addressed with a focus on three agents, Saccharomyces boulardii, Lactobacillus rhamnosus GG and the combination of Lactobacillus acidophilus CL1285, Lactobacillus casei LBC80R, Lactobacillus rhamnosus CLR2 (Bio-K+).
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Infecções por Clostridium/prevenção & controle , Probióticos/administração & dosagem , Infecções por Clostridium/economia , Análise Custo-Benefício , Humanos , Lactobacillus acidophilus/crescimento & desenvolvimento , Lacticaseibacillus casei/crescimento & desenvolvimento , Lacticaseibacillus rhamnosus/crescimento & desenvolvimento , Probióticos/economia , Saccharomyces boulardii/crescimento & desenvolvimentoRESUMO
OBJECTIVE: We sought to determine the economic costs associated with moderate and late preterm birth. DESIGN: An economic study was nested within a prospective cohort study. SAMPLE: Infants born between 32(+0) and 36(+6) weeks of gestation in the East Midlands of England. A sample of infants born at ≥37 weeks of gestation acted as controls. METHODS: Data on resource use, estimated from a National Health Service (NHS) and personal social services perspective, and separately from a societal perspective, were collected between birth and 24 months corrected age (or death), and valued in pounds sterling, at 2010-11 prices. Descriptive statistics and multivariable analyses were used to estimate the relationship between gestational age at birth and economic costs. MAIN OUTCOME MEASURES: Cumulative resource use and economic costs over the first two years of life. RESULTS: Of all eligible births, 1146 (83%) preterm and 1258 (79%) term infants were recruited. Mean (standard error) total societal costs from birth to 24 months were £12 037 (£1114) and £5823 (£1232) for children born moderately preterm (32(+0) -33(+6) weeks of gestation) and late preterm (34(+0) -36(+6) weeks of gestation), respectively, compared with £2056 (£132) for children born at term. The mean societal cost difference between moderate and late preterm and term infants was £4657 (bootstrap 95% confidence interval, 95% CI £2513-6803; P < 0.001). Multivariable regressions revealed that, after controlling for clinical and sociodemographic characteristics, moderate and late preterm birth increased societal costs by £7583 (£874) and £1963 (£337), respectively, compared with birth at full term. CONCLUSIONS: Moderate and late preterm birth is associated with significantly increased economic costs over the first 2 years of life. Our economic estimates can be used to inform budgetary and service planning by clinical decision-makers, and economic evaluations of interventions aimed at preventing moderate and late preterm birth or alleviating its adverse consequences. TWEETABLE ABSTRACT: Moderate and late preterm birth is associated with increased economic costs over the first 2 years of life.
Assuntos
Idade Gestacional , Nascimento Prematuro/economia , Estudos de Casos e Controles , Serviços de Saúde da Criança/economia , Serviços de Saúde da Criança/estatística & dados numéricos , Pré-Escolar , Serviços de Saúde Comunitária/economia , Serviços de Saúde Comunitária/estatística & dados numéricos , Custos de Medicamentos/estatística & dados numéricos , Inglaterra/epidemiologia , Licença para Cuidar de Pessoa da Família/economia , Feminino , Custos Hospitalares/estatística & dados numéricos , Humanos , Lactente , Recém-Nascido , Tempo de Internação/economia , Tempo de Internação/estatística & dados numéricos , Gravidez , Nascimento Prematuro/epidemiologia , Estudos ProspectivosRESUMO
BACKGROUND: BRAF V600E mutation has been reported to show a high specificity for papillary thyroid carcinoma (PTC). Using this marker to upgrade 'indeterminate' or 'suspicious' thyroid fine needle aspiration (FNA) cytology to 'malignant' could potentially allow one-stage therapeutic total thyroidectomy. METHODS: For a 14-month period, FNA cytology specimens in the Thy3-5 categories, which are the UK equivalents of indeterminate (Thy3a, atypical; Thy3f, follicular), suspicious for malignancy (Thy4) and malignant (Thy5) in the Bethesda System, underwent BRAF mutation testing by melt curve analysis. The results were correlated with histology. RESULTS: We tested 123 cytology specimens of which 12 (9.8%) failed. The BRAF mutation rate in the remainder was 16.2% (18/111), with 93 showing the wild-type. Seventeen mutations were V600E and one was non-V600E. The rate of mutation increased significantly (P < 0.0001 if Thy3a and Thy3f were combined) with the cytology category: 1/42 Thy3a (2.4%), 1/36 Thy3f (2.8%), 4/15 Thy4 (26.7%), 12/18 Thy5 (66.7%). All BRAF mutations correlated with PTC on histology, except for one recurrent PTC without histology. One mutation-positive case with Thy3a cytology showed the target lesion to be a 10-mm follicular adenoma on histology with an immediately adjacent 4-mm micro-PTC, in a patient who did not require total thyroidectomy. CONCLUSION: BRAF mutational analysis by melt curve analysis is feasible in routine thyroid cytology, and in our series had a 100% specificity for PTC in subsequent histology. The application of BRAF analysis could be useful for indeterminate cytology, but we suggest that it would be most appropriate and cost-effective for Thy4/suspicious cases, for which it could enable one-stage therapeutic surgery in the context of multidisciplinary discussion. In contrast, the sensitivity is low and there is no role for avoiding diagnostic thyroid surgery if wild-type BRAF is found.
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Biópsia por Agulha Fina , Carcinoma/genética , Proteínas Proto-Oncogênicas B-raf/genética , Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/genética , Carcinoma/patologia , Carcinoma Papilar , Análise Mutacional de DNA , Humanos , Mutação , Estadiamento de Neoplasias , Desnaturação de Ácido Nucleico/genética , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide/patologia , Nódulo da Glândula Tireoide/genética , Nódulo da Glândula Tireoide/patologiaRESUMO
OBJECTIVE: Ultrasound elastography (USE) assesses lesion stiffness by evaluating tissue distortion in response to stress; it is emerging as a potentially useful tool to augment the ultrasound characterisation of thyroid nodules. The aim of this study was to assess the accuracy of USE examination of thyroid nodules compared with pathological outcome, especially to determine whether USE could reliably detect benign nodules and reduce the numbers of ultrasound guided fine needle aspiration cytology (USgFNAC). DESIGN: Over a three-year period, thyroid nodules were initially characterised by B-mode ultrasound (US) findings. Where USgFNAC was indicated by clinical concern and/or the sonographic appearances, the lesion was then subjected to USE by an experienced operator prior to the USgFNAC. PATIENTS: 147 thyroid nodules were examined by USE and USgFNAC in 146 patients. MEASUREMENTS: The elastographic appearance was subjectively categorized at the time of the examination (soft, intermediate or hard) and subsequently compared with the cytological/histological outcome. RESULTS: A total of 122 nodules were non-neoplastic, 5 nodules were benign neoplasms, 10 nodules had indeterminate cytology and 10 were malignant neoplasms. The sensitivity of USE for malignancy was 90.0%, specificity was 79.6%, PPV was 24.3%, NPV was 99.1% and accuracy was 80.3%. CONCLUSION: Thyroid nodules that are soft at USE have a high likelihood of being non-neoplastic and subjective USE assessment of thyroid nodules by an experienced operator can be a useful means of avoiding USgFNAC for benign nodules. In contrast, we suggest that all nodules that are intermediate or hard on USE undergo USgFNAC.
Assuntos
Biópsia por Agulha Fina , Técnicas de Imagem por Elasticidade , Nódulo da Glândula Tireoide/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Nódulo da Glândula Tireoide/diagnóstico por imagemRESUMO
INTRODUCTION: Return-to-work (RTW) status is an often used outcome in work and health research. In low back pain, work is regarded as a normal activity a worker should return to in order to fully recover. Comparing outcomes across studies and even jurisdictions using different definitions of RTW can be challenging for readers in general and when performing a systematic review in particular. In this study, the measurement properties of previously defined RTW outcomes were examined with data from two studies from two countries. METHODS: Data on RTW in low back pain (LBP) from the Canadian Early Claimant Cohort (ECC); a workers' compensation based study, and the Dutch Amsterdam Sherbrooke Evaluation (ASE) study were analyzed. Correlations between outcomes, differences in predictive validity when using different outcomes and construct validity when comparing outcomes to a functional status outcome were analyzed. RESULTS: In the ECC all definitions were highly correlated and performed similarly in predictive validity. When compared to functional status, RTW definitions in the ECC study performed fair to good on all time points. In the ASE study all definitions were highly correlated and performed similarly in predictive validity. The RTW definitions, however, failed to compare or compared poorly with functional status. Only one definition compared fairly on one time point. CONCLUSIONS: Differently defined outcomes are highly correlated, give similar results in prediction, but seem to differ in construct validity when compared to functional status depending on societal context or possibly birth cohort. Comparison of studies using different RTW definitions appears valid as long as RTW status is not considered as a measure of functional status.
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Dor Lombar/reabilitação , Doenças Profissionais/reabilitação , Licença Médica , Trabalho , Indenização aos Trabalhadores , Adolescente , Adulto , Canadá , Avaliação da Deficiência , Emprego , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Psicometria , Reprodutibilidade dos Testes , Inquéritos e Questionários , Adulto JovemRESUMO
We describe two unrelated men who both developed teratomas in one testis followed by seminomas in the contralateral testis followed by papillary thyroid carcinomas. Neither man had a family history of cancers. Although random occurrence is possible, genetic predisposition and/or environmental influence would seem a likely explanation for this previously unreported combination of tumours.
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Carcinoma Papilar/patologia , Neoplasias Primárias Múltiplas/patologia , Seminoma/patologia , Teratoma/patologia , Neoplasias Testiculares/patologia , Neoplasias da Glândula Tireoide/patologia , Adulto , Carcinoma Papilar/terapia , Humanos , Masculino , Neoplasias Primárias Múltiplas/terapia , Seminoma/terapia , Teratoma/terapia , Neoplasias Testiculares/terapia , Neoplasias da Glândula Tireoide/terapia , Resultado do Tratamento , Adulto JovemRESUMO
Calcitonin-negative medullary thyroid carcinoma is a rare, poorly understood primary neuroendocrine carcinoma of the thyroid characterised by classic medullary thyroid carcinoma morphology without raised serum calcitonin. A 24-year-old woman presented with a slow-growing, right-sided neck swelling. She underwent an ultrasound scan, cytopathological and histopathological examination, and tests for alternative diagnoses. The ultrasound showed a heterogeneous, hyperechoic nodule in the right thyroid lobe. Serum calcitonin was normal. Cytopathology and histopathology showed typical medullary thyroid carcinoma morphology but without calcitonin upon immunostaining and mRNA in situ hybridisation. A 'triple-negative' calcitonin-negative medullary thyroid carcinoma was diagnosed. A completion thyroidectomy with bilateral central lymph node dissection was performed. The patient remains well three-years post-surgery. When cytopathology suggests a medullary thyroid carcinoma, serum calcitonin, pro-calcitonin, carcinoembryonic antigen and calcitonin-gene-related peptide should be measured to identify cases of calcitonin-negative medullary thyroid carcinoma. They should also be measured post-treatment for monitoring purposes. This will aid future calcitonin-negative medullary thyroid carcinoma diagnoses and will inform prognostic stratification and influence treatment decisions.
Assuntos
Calcitonina/sangue , Carcinoma Neuroendócrino/sangue , Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/sangue , Biomarcadores Tumorais/sangue , Biópsia , Carcinoma Neuroendócrino/diagnóstico , Carcinoma Neuroendócrino/cirurgia , Feminino , Humanos , Fenótipo , Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia/métodos , Tomografia Computadorizada por Raios X , Ultrassonografia , Adulto JovemRESUMO
While social experience has been shown to significantly alter behaviors in a wide range of species, comparative studies that uniformly measure the impact of a single experience across multiple species have been lacking, limiting our understanding of how plastic traits evolve. To address this, we quantified variations in social feeding behaviors across 10 species of Drosophilids, tested the effect of altering rearing context on these behaviors (reared in groups or in isolation) and correlated observed behavioral shifts to accompanying transcriptional changes in the heads of these flies. We observed significant variability in the extent of aggressiveness, the utilization of social cues during food search, and social space preferences across species. The sensitivity of these behaviors to rearing experience also varied: socially naive flies were more aggressive than their socialized conspecifics in some species, and more reserved or identical in others. Despite these differences, the mechanism of socialization appeared to be conserved within the melanogaster subgroup as species could cross-socialize each other, and the transcriptional response to social exposure was significantly conserved. The expression levels of chemosensory-perception genes often varied between species and rearing conditions, supporting a growing body of evidence that behavioral evolution is driven by the differential regulation of this class of genes. The clear differences in behavioral responses to socialization observed in Drosophilids make this an ideal system for continued studies on the genetic basis and evolution of socialization and behavioral plasticity.
Assuntos
Drosophila/genética , Evolução Molecular , Comportamento Social , Transcriptoma , Animais , Drosophila/classificação , Drosophila/fisiologia , Comportamento AlimentarRESUMO
The histopathological features of thyroid cancers can be used to risk stratify patients, allowing prognostication and treatment decisions. A detailed accurate histological assessment by experienced pathologists working within a multidisciplinary context is crucial. Experience is also essential for interpretation of preoperative thyroid cytology specimens, which can be challenging. There is now more international harmonisation of numerical reporting systems for thyroid cytology. Understanding of the molecular basis of thyroid cancer has increased dramatically in recent years. Preoperative molecular pathology testing, when available, can refine cytological diagnosis to rule in or out for surgery, as well as assisting prognostication and enabling targeted treatment for thyroid tumours.
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Biópsia por Agulha Fina/métodos , Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/patologia , HumanosRESUMO
INTRODUCTION Neuroendocrine tumours (NETs) are a heterogeneous group of tumours with a highly variable presentation and prognosis. Management decisions are complex. Ki-67 levels in tissue samples are a key indicator used to grade tumours and guide treatment. This study assessed whether the Ki-67 index and tumour grade generated from tissue samples correlated with that assessed in resection specimens. METHODS This was a retrospective cohort analysis of all patients who had both a tissue sample and a resection specimen analysed in our trust, a tertiary referral centre, during 2012 and 2013. RESULTS Data from 36 patients were reviewed. Ki-67 indices from tissue samples and resection specimens showed strong correlation (r=0.95, p<0.001). Tumour grading was the same in the tissue sample and resection specimens for 22 patients (61.1%). In four patients (11.1%), the tissue sample overestimated the grade while in ten (27.8%), the sample underestimated the grade. CONCLUSIONS In most cases, the Ki-67 index and tumour grade from the tissue sample matched that of the resection specimen. However, in nearly 40% of cases, the tissue sample grading did not match the resection tumour grading. In the majority of these, the tissue sample underestimated disease activity. A low Ki-67 index in a tissue sample should therefore be taken as provisional and should not, in isolation, persuade clinicians to choose a more conservative treatment approach if there is clinical, biochemical or radiological evidence suggestive of a more aggressive disease pathology.
Assuntos
Neoplasias do Sistema Digestório/metabolismo , Antígeno Ki-67/metabolismo , Neoplasias Pulmonares/metabolismo , Tumores Neuroendócrinos/metabolismo , Adulto , Idoso , Biópsia por Agulha Fina , Biópsia com Agulha de Grande Calibre , Estudos de Coortes , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Neoplasias do Sistema Digestório/patologia , Neoplasias do Sistema Digestório/cirurgia , Feminino , Humanos , Neoplasias do Íleo/metabolismo , Neoplasias do Íleo/patologia , Neoplasias do Íleo/cirurgia , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Tumores Neuroendócrinos/patologia , Tumores Neuroendócrinos/cirurgia , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgiaRESUMO
AIMS: The Royal College of Pathologists Thy1-5 thyroid cytology guidance, 2009, second edition 2016, invites audits of its use. This report documents the experience of one department, assessing percentage usage of each Thy category, correlation with subsequent histology and comparison with other published studies. METHODS: Thyroid cytology and subsequent histology reports for 7â years (1 January 2008-31 December 2014) were reviewed, excluding referrals. Years 2008-2010 were compared with 2011-2014. RESULTS: There were 1090 specimens in 2008-2010, 1239 in 2011-2014. Thy usage for 2008-2010/2011-2014, respectively was: Thy1 16.1%/9.8%; Thy1c 10.6%/10.7%; Thy2/2c 52.4%/45.2%; Thy3a 9.6%/14.4%; Thy3f 5.8%/10.9%; Thy4 2.3%/3.6%; Thy5 1.8%/5.4%. 772 specimens had subsequent histology: 415 non-neoplastic lesions; 357 neoplasms (110 benign, 247 malignant). Risk of malignancy (ROM) (including non-histology cases) for 2008-2010/2011-2014: Thy1/1c 5.2%/4.0%; Thy2/2c 1.4%/1.4%; Thy3a 10.0%/14.5%; Thy3f 25.4%/26.7%. Positive predictive values (PPVs) for neoplasia (histology cases only): Thy3a 20.3%/56.9%; Thy3f 60.0%/64.8%; Thy4 58.3%/90.9%; Thy5 100%/100%. PPVs for malignancy (histology cases only): Thy3a 10.2%/36.1%; Thy3f 35.4%/33.3%; Thy4 50.0%/81.8%; Thy5 100%/100%. The Thy3a/Thy5 ratio for 2011-2014 was 2.7. CONCLUSIONS: Numerical reporting categories facilitate audit and comparison with other published results. Technique-related inadequates (Thy1) have reduced but cystic lesions (Thy1c) are stable, in keeping with increased use of ultrasound scanning (USS). Thy2/2c has reduced, probably reflecting increased USS selection of non-benign nodules for sampling. ROMs for Thy1/1c/2/2c are low. Usage of all positive categories, Thy3a, Thy3f, Thy4 and Thy5, has increased. As others have reported for atypia of undetermined significance or follicular lesion of undetermined significance, Thy3a is followed by malignancy more frequently than expected. There is stable prediction of malignancy by Thy3f and Thy5, the latter being 100% throughout.
Assuntos
Glândula Tireoide/patologia , Nódulo da Glândula Tireoide/patologia , Diagnóstico Diferencial , Humanos , Estudos Retrospectivos , Fatores de Risco , Sensibilidade e Especificidade , Terminologia como Assunto , Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/patologia , Nódulo da Glândula Tireoide/diagnóstico por imagem , UltrassonografiaRESUMO
Intrinsic Optical Signal (IOS) imaging has been used extensively to examine activity-related changes within the cerebral cortex. A significant technical challenge with IOS imaging is the presence of large noise, artefact components and periodic interference. Signal processing is therefore important in obtaining quality IOS imaging results. Several signal processing techniques have been deployed, however, the performance of these approaches for IOS imaging has never been directly compared. The current study aims to compare signal processing techniques that can be used when quantifying stimuli-response IOS imaging data. Data were gathered from the somatosensory cortex of mice following piezoelectric stimulation of the hindlimb. The effectiveness of each technique to remove noise and extract the IOS signal was compared for both spatial and temporal responses. Careful analysis of the advantages and disadvantages of each method were carried out to inform the choice of signal processing for IOS imaging. We conclude that spatial Gaussian filtering is the most effective choices for improving the spatial IOS response, whilst temporal low pass and bandpass filtering produce the best results for producing temporal responses when periodic stimuli are an option. Global signal regression and truncated difference also work well and do not require periodic stimuli.
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OBJECTIVE: To describe the distribution and prevalence of cattle herds with detectable antibody to bovine pestivirus in Queensland in 1994/95. MATERIALS AND METHODS: The study used 7,838 serum samples collected from 250 herds in Queensland, as part of a structured animal health surveillance program conducted in 1994 and 1995. Samples were collected from female cattle bred on the property. In each herd, 10 to 20 heifers less than two years of age and 10 to 15 older cows were sampled giving a 95% probability of detecting one or more seropositive animals if the seroprevalence was approximately 10% or greater. Sera were analysed for antibodies to bovine pestivirus using a virus neutralisation test. RESULTS: Total cattle numbers in sampled herds varied from 62 to 24,600 head, while total area of properties sampled varied from 50 to 395,400 hectares. Eleven percent of herds contained no seropositive animals among those sampled, and in 38% of herds, all sampled cattle aged one to two years of age were seronegative. There was a trend for larger herds to have one or more animals seropositive for bovine pestivirus (chi-squared for Linear trend = 3.656, p = 0.056). Herds with more than 500 head of cattle were significantly more likely than herds with less than 500 head to contain one or more seropositive animals in any age group (prevalence ratio = 1.12; 95% confidence interval 1.01 - 1.23; p = 0.026). Age specific seroprevalence increased from around 10% in heifers, to between 75% and 85% in cows aged 10 years. The average annual incidence risk for bovine pestivirus infection varied from 0.12 to 0.24 seroconversions per cattle year at risk, and did not vary with age. The overall crude seroprevalence adjusted for herd size was 45%. There was a wide range of seroprevalence recorded for each level of stocking intensity. CONCLUSIONS: This survey provides valuable baseline data on bovine pestivirus infection in Queensland cattle herds.
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Anticorpos Antivirais/sangue , Doença das Mucosas por Vírus da Diarreia Viral Bovina/epidemiologia , Vírus da Diarreia Viral Bovina/imunologia , Animais , Bovinos , Feminino , Queensland/epidemiologia , Estudos SoroepidemiológicosRESUMO
The purpose of this study was to examine the frequency and nature of falls and fall-related injuries among older women in the state of Kerala, India. The study involved 82 community living and 63 institutionalized women aged 60 years or older in Trivandrum, Kerala, India. Demographic data and falls profile were collected through the use of a field survey. A significantly lower percentage (45%) of community dwelling participants suffered a fall in the previous year, compared to 64% of those in the Long Term Care (LTC) settings (p < .05). Overall, of those who fell, 74% reported an injury (e.g., cuts and bruises, fractures) as a result of the fall, and 48% of older adults in the community and 70% in the LTC setting required medical treatment as a result of the falls. Falling is emerging as a significant public health problem facing older women in the state of Kerala. Fall prevention strategies to address falls should be explored and implemented within the Indian context.
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Acidentes por Quedas/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Índia/epidemiologia , Pessoa de Meia-Idade , Características de Residência , Fatores Socioeconômicos , Ferimentos e Lesões/epidemiologiaRESUMO
The pathological examination of parathyroid glands is an essential component of the evaluation of hyperparathyroidism. Traditionally, this has involved intraoperative frozen sections during bilateral surgical exploration of the neck, to confirm removal of parathyroid tissue. With recent developments in imaging, some diseased glands can be localised preoperatively, enabling removal by minimally invasive, targetted surgery, with or without additional non-histological intraoperative procedures to confirm the removal of all hyperfunctioning parathyroid tissue. This article reviews these developments and describes the ideal approach to reporting parathyroid specimens.
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Hiperparatireoidismo/patologia , Glândulas Paratireoides/patologia , Adenoma/diagnóstico , Adenoma/patologia , Criopreservação/métodos , Diagnóstico Diferencial , Humanos , Hiperparatireoidismo/diagnóstico , Hiperplasia/diagnóstico , Cuidados Intraoperatórios/métodos , Neoplasias das Paratireoides/diagnóstico , Neoplasias das Paratireoides/patologia , Cuidados Pré-Operatórios/métodosRESUMO
BACKGROUND AND AIM: Freehand fine needle aspiration cytology (FNAC) is an obligatory investigation of the thyroid nodule. Between 5.0-43.1% of FNAC samples are reported as being initially unsatisfactory. In our unit, thyroid freehand FNAs are performed with a small needle (21 or 23G). Non-dominant nodules as part of multinodular goitres, difficult to palpate nodules or nodules with previously unsatisfactory freehand FNACs are sampled under ultrasound scan (USS) guidance with the larger 20G cutting core sampling technique. We aimed to compare the satisfactory sampling rate and safety of the two different methods. PATIENTS AND METHODS: Cytology forms were reviewed for 262 freehand FNACs and USS-guided core samples, performed in our unit over a two-year interval (1 July 1999 to 30 June 2001). RESULTS: Ultrasound-guided core samples for cytology were unsatisfactory (AC0-1) in 19/121 (15.6%) of the cases, compared with 66/141 (46.8%) of freehand FNACs (p value = < 0.0001). Ten out of eleven patients (91%) had a satisfactory USS-guided core after an unsatisfactory freehand FNA; 7/15 patients (46.7%) had satisfactory repeat freehand FNACs following an initial unsatisfactory freehand FNAC (p value = 0.0191). There were no complications as a result of either freehand FNAC or USS-guided core sampling. CONCLUSION: USS-guided cores provided more satisfactory samples for assessment than freehand FNACs. The USS-guided technique is safe despite the use of the larger cuffing needle. The USS-guided core sampling was also a useful tool for repeat thyroid nodule sampling after an unsatisfactory freehand FNAC.
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Biópsia por Agulha/métodos , Glândula Tireoide/patologia , Nódulo da Glândula Tireoide/patologia , Biópsia por Agulha Fina , Humanos , Auditoria Médica , Viés de Seleção , Resultado do Tratamento , Ultrassonografia/métodosRESUMO
Sickness behaviors have become the focus of great interest in recent years as they represent a clear case of how peripheral disturbances in immune signaling can disrupt quite complex behaviors. In the current study, we were interested in examining whether we could identify any significant morphological disturbances in microglia associated with these sickness-like behaviors in adult male Sprague-Dawley rats. We chose lipopolysaccharide (LPS 100 µg/kg/i.p.), to induce sickness-like behaviors as it is the most well-validated approach to do so in rodents and humans. We were particularly interested in examining changes in microglia within the prefrontal cortex (PFC) as several recent neuroimaging studies have highlighted significant functional changes in this region following peripheral LPS administration. Paraformaldehyde-fixed tissue was collected from animals 24h post LPS administration and labeled immunohistochemically with an antibody directed to bind to Iba-1, a protein known to be involved in the structural remodeling of microglia. To analyze changes, we have made use of two recently described image analysis procedures. The first is known as cumulative threshold spectra (CTS) analysis. The second involves the unsupervised digital reconstruction of microglia. We undertook these complementary analysis of microglial cells in the both the pre- and infralimbic divisions of the PFC. Our results indicated that microglial soma size was significantly enlarged, while cell processes had contracted slightly following LPS administration. To our knowledge this study is to first to definitely demonstrate substantial microglial disturbances within the PFC following LPS delivered at a dose that was sufficient to induce significant sickness-like behavior.
Assuntos
Comportamento de Doença/fisiologia , Lipopolissacarídeos/administração & dosagem , Microglia/citologia , Microglia/efeitos dos fármacos , Córtex Pré-Frontal/citologia , Córtex Pré-Frontal/efeitos dos fármacos , Animais , Peso Corporal/efeitos dos fármacos , Ingestão de Alimentos/efeitos dos fármacos , Processamento de Imagem Assistida por Computador/métodos , Imuno-Histoquímica/métodos , Masculino , Atividade Motora/efeitos dos fármacos , Ratos , Ratos Sprague-DawleyRESUMO
Point mutations of G protein genes that result in the constitutive activation of G proteins have been described. Such mutations have been shown to occur in a number of endocrine diseases. We have examined tissues from patients having more than one organ affected by an endocrine disorder and patients having separate distinct endocrine diseases for G protein gene mutations. G protein genes encoding for Gs alpha and Gi2 alpha were examined for activating mutations at codons 201 and 227 (Gs alpha) and codons 179 and 205 (Gi2 alpha) using site-directed oligonucleotide hybridization and direct sequencing of tissue DNA amplified by polymerase chain reaction. Tissues from six patients were examined. The only mutation that was identified was at codon 201 of Gs alpha (gsp), which encoded a change from arginine to cysteine. Patient 1 had the mutation in a corticotroph adenoma, a chemodectoma, and a nodular hyperplastic adrenal gland. patient 2 had the mutation in an extraadrenal pheochromocytoma, but an adrenal gland with medullary hyperplasia was wild-type. Patient 3 had an aggressive corticotroph adenoma and developed Nelson's syndrome after bilateral adrenalectomy. The corticotroph adenoma was wild-type, but both hyperplastic adrenal glands had the mutation. Patient 4 had the mutation in a parathyroid adenoma and in two hyperplastic parathyroid glands. Patient 5 had the mutation in both a primary and a metastatic pheochromocytoma. Patient 6 had the mutation in a parathyroid adenoma and also in histologically normal thyroid and parathyroid tissue. Leukocyte DNA was examined from five patients and was found to be wild-type in all cases. We conclude that G protein gene mutations occur in a wider range of endocrine conditions than has been recognized hereto. In addition, the presence of gsp mutations in different endocrine disorders in the same patient is suggestive of a common underlying etiology.
Assuntos
Proteínas de Ligação ao GTP/genética , Neoplasia Endócrina Múltipla/genética , Mutação , Adulto , Sequência de Bases , DNA de Neoplasias/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sondas Moleculares/genética , Dados de Sequência MolecularRESUMO
The discovery of a series of chromen-2-ones with selective affinity for the dopamine (DA) D4 receptor is described. Target compounds were tested for binding to cloned human DA D2L, D3, and D4.2 receptor subtypes expressed in Chinese hamster ovary K1 cells. Several compounds demonstrated high affinity (<20 nM, K(i)) and greater than 100-fold selectivity for DA D4.2 versus DA D2L receptors. The results of a SAR study are discussed within. In a DA D4 functional assay measuring [(3)H]thymidine uptake, target compounds showed antagonist activity at the D4.2 receptor. Compound 22, 7-[(2-phenylaminoethylamino)methyl]chromen-2-one, increased DOPA (L-3,4-dihydroxyphenylalanine) accumulation 51% in the hippocampus and 23% in the striatum of rat brains when dosed orally at 20 mg/kg.
Assuntos
Antipsicóticos/síntese química , Benzopiranos/síntese química , Antagonistas de Dopamina/síntese química , Antagonistas dos Receptores de Dopamina D2 , Piperazinas/síntese química , Animais , Antipsicóticos/farmacologia , Benzopiranos/farmacologia , Células CHO , Cricetinae , Dopamina/biossíntese , Antagonistas de Dopamina/farmacologia , Desenho de Fármacos , Humanos , Camundongos , Atividade Motora/efeitos dos fármacos , Piperazinas/farmacologia , Ligação Proteica , Ratos , Receptores de Dopamina D4 , Reflexo de Sobressalto/efeitos dos fármacos , Esquizofrenia/tratamento farmacológico , Relação Estrutura-AtividadeRESUMO
A novel dopamine (DA) autoreceptor agonist, 1,2,3,6-tetrahydro-4-phenyl-1- [(3-phenyl-3-cyclohexen-1-yl)methyl]pyridine (14), was identified. The structure-activity relationships surrounding this compound were studied by synthesis of analogues and evaluation of their dopaminergic activity. The cyclohexene substitution pattern was varied along with the length of the chain connecting the 1,2,3,6-tetrahydro-4-phenylpyridine to the cyclohexene. Compound 14, having the 1,3-substitution pattern and a single methylene chain, was the most potent. The 1,2,3,6-tetrahydro-4-phenylpyridine could be replaced by other aryl-cyclic amines with a slight loss in activity. The phenyl group on the cyclohexene ring could be para substituted; electron-donating groups were better tolerated than electron-withdrawing groups. Finally, the enantiomers of 14 were resolved via the 1,1'-binaphthyl-2,2'-diyl hydrogen phosphate salts. Although both isomers were partial DA agonists, the (+)-enantiomer had higher intrinsic activity than the (-)-enantiomer. Syntheses were developed that allowed rapid preparation of analogues. An X-ray crystal structure determination of an intermediate identified the (+)-isomer of 14 as having R configuration. This compound, designated CI-1007 (PD 143188), was found to have antipsychotic-like activity in behavioral tests; in particular, it was orally active in the conditioned avoidance test in squirrel monkeys with an ED50 of 0.6 mg/kg. The overall profile suggests that (R)-(+)-14 may be a clinically useful antipsychotic agent.