RESUMO
OBJECTIVES: The effects of trigger point dry needling (TDN) on myofascial trigger points (MTP) in Achilles tendinopathy (AT) are unknown. We conducted a study to test the feasibility of a large randomized controlled trial (RCT) to compare the effects of TDN to MT and exercise in a patient population with AT. METHODS: Twenty-two subjects were randomly assigned to a control (MT+Ex) or experimental group (TDN+MT+Ex) and completed eight treatment sessions over 4 weeks with follow up at 3 months. TDN was performed to MTPs in the gastrocnemius, soleus or tibialis posterior each session. The same MT and exercise program was conducted in both groups. RESULTS: Two of three criteria for feasibility were met. The attrition rate at 4-week and 3-month follow-up was 18.1% and 68%, respectively. Significant differences (p < .05) reported for within group analysis for FAAM, NPRS, pain pressure threshold and strength in both groups at 4 weeks and 3 months. The GROC was significant for MT + Ex at 3 months. No between group differences were found. The MCID for the FAAM, GROC was surpassed in both groups at 4 weeks and 3 months and NPRS for the MT + Ex group at 4 weeks. DISCUSSION: A large RCT to investigate the effects of TDN on MTP in AT is not feasible without modifications due to low recruitment and high attrition rate. Modifications to study design should give consideration for closed or national health-care system for access to large patient populations and reduced financial burden to subjects. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03261504F.
Assuntos
Tendão do Calcâneo/fisiopatologia , Agulhamento Seco/métodos , Terapia por Exercício/métodos , Manipulações Musculoesqueléticas/métodos , Tendinopatia/terapia , Adulto , Idoso , Terapia Combinada , Estudos de Viabilidade , Humanos , Pessoa de Meia-Idade , Tendinopatia/fisiopatologia , Adulto JovemRESUMO
OBJECTIVES: To report outcome data on the first 5000 consecutive cataract cases at a new paperless eye unit and benchmark against the Royal College of Ophthalmologists' National Ophthalmology Database (RCOphth NOD). METHODS: Using the in-built audit tool of the electronic medical records system, data from all cataract operations performed between 1 April 2014 and 13 January 2017 were compiled. RESULTS: Five thousand and eight cases were recorded of which the overall intra-operative complication rate was 2.4%, the most common being posterior capsular rupture-1.14%. Follow-up data on post-operative complications were recorded in 98.6% of cases. Pre- and post-operative visual acuities was measured in 98.0% of cases. In all, 40.8% of eyes achieved a visual acuity of 6/6 or better and 90.7% achieved 6/12 or better. CONCLUSIONS: A data set of >5000 consecutive cataract operations was obtained in this eye department. The recording of pre- and post-operative visual acuity in 98% of cases compare very favourably to the RCOphth NOD Audit Report 2017 where pre- and post-operative visual acuities were recorded in only 57.1% of operations. Despite this difference, the outcome measures from this unit and RCOphth NOD were very similar, validating the results of the RCOphth NOD audit reports. Significantly, when applying the RCOphth NOD audit criteria for measuring post-operative visual acuity, approximately 15% of cases were excluded from the data set, reducing the completeness of the data set. Paperless ophthalmology units are feasible in today's NHS and can produce near complete cataract data sets; this can ultimately lead to more comprehensive and reliable aggregate cataract outcome data.
Assuntos
Extração de Catarata/estatística & dados numéricos , Registros Eletrônicos de Saúde/organização & administração , Complicações Intraoperatórias/epidemiologia , Oftalmologia/estatística & dados numéricos , Complicações Pós-Operatórias/epidemiologia , Melhoria de Qualidade , Sistema de Registros , Idoso , Confiabilidade dos Dados , Feminino , Seguimentos , Humanos , Incidência , Masculino , Estudos Retrospectivos , Reino Unido/epidemiologia , Acuidade VisualRESUMO
BACKGROUND AND PURPOSE: Differences in structural brain connectivity that underlie inattention have been previously investigated in adolescents with attention deficit/hyperactivity disorder, but not in the context of premature birth, which is often associated with attentional problems. The purpose of this study was to identify the neural correlates of attentional problems in adolescents born prematurely and determine neonatal predictors of those neural correlates and attention problems. MATERIALS AND METHODS: The study included 24 adolescents (12.5 ± 1.8 years of age; 12 girls, 12 boys) who were born prematurely and underwent MR imaging of the brain and cognitive assessment, both shortly after birth and as adolescents. Structural connectivity was assessed at adolescence using diffusion tensor imaging and tractography. RESULTS: Of the 24 subjects, 12 had attention deficits. A set of axonal pathways connecting the frontal, parietal, temporal, and occipital lobes had significantly lower fractional anisotropy in subjects with attentional problems. The temporoparietal connection between the left precuneus and left middle temporal gyrus was the most significantly underconnected interlobar axonal pathway. Low birth weight and ventriculomegaly, but not white matter injury or intraventricular hemorrhage on neonatal MR imaging, predicted temporoparietal hypoconnectivity in adolescence. However, neither birth weight nor other neonatal characteristics were associated with attention deficits directly. CONCLUSIONS: We identified an aberrant structural brain connectivity pattern, involving temporoparietal hypoconnectivity, in prematurely born adolescents with attentional problems. We also identified birth weight as a potential neonatal predictor of the temporoparietal hypoconnectivity. These findings add to our understanding of the neural basis and etiology of inattention in adolescents after premature birth.
Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/patologia , Encéfalo/patologia , Vias Neurais/patologia , Nascimento Prematuro , Adolescente , Transtorno do Deficit de Atenção com Hiperatividade/etiologia , Mapeamento Encefálico/métodos , Criança , Imagem de Tensor de Difusão , Feminino , Humanos , Recém-Nascido , Masculino , GravidezRESUMO
Laguna Bacalar is a sulfate-rich freshwater lake on the Yucatan Peninsula that hosts large microbialites. High sulfate concentrations distinguish Laguna Bacalar from other freshwater microbialite sites such as Pavilion Lake and Alchichica, Mexico, as well as from other aqueous features on the Yucatan Peninsula. While cyanobacterial populations have been described here previously, this study offers a more complete characterization of the microbial populations and corresponding biogeochemical cycling using a three-pronged geobiological approach of microscopy, high-throughput DNA sequencing, and lipid biomarker analyses. We identify and compare diverse microbial communities of Alphaproteobacteria, Deltaproteobacteria, and Gammaproteobacteria that vary with location along a bank-to-bank transect across the lake, within microbialites, and within a neighboring mangrove root agglomeration. In particular, sulfate-reducing bacteria are extremely common and diverse, constituting 7%-19% of phylogenetic diversity within the microbialites, and are hypothesized to significantly influence carbonate precipitation. In contrast, Cyanobacteria account for less than 1% of phylogenetic diversity. The distribution of lipid biomarkers reflects these changes in microbial ecology, providing meaningful biosignatures for the microbes in this system. Polysaturated short-chain fatty acids characteristic of cyanobacteria account for <3% of total abundance in Laguna Bacalar microbialites. By contrast, even short-chain and monounsaturated short-chain fatty acids attributable to both Cyanobacteria and many other organisms including types of Alphaproteobacteria and Gammaproteobacteria constitute 43%-69% and 17%-25%, respectively, of total abundance in microbialites. While cyanobacteria are the largest and most visible microbes within these microbialites and dominate the mangrove root agglomeration, it is clear that their smaller, metabolically diverse associates are responsible for significant biogeochemical cycling in this microbialite system.
Assuntos
Bactérias/classificação , Biodiversidade , Biomarcadores/análise , Água Doce/microbiologia , Sedimentos Geológicos/microbiologia , Lipídeos/análise , Bactérias/química , Bactérias/citologia , Sequenciamento de Nucleotídeos em Larga Escala , México , MicroscopiaRESUMO
BACKGROUND: Universal newborn hearing screening (UNHS) targets moderate or greater hearing loss. However, UNHS also frequently detects children with mild loss that results in many receiving early treatment. The benefits of this approach are not yet established. We aimed to (i) compare language and psychosocial outcomes between four hearing loss detection systems for children aged 5-8 years with congenital mild-moderate hearing loss; (ii) determine whether age of detection predicts outcomes; and (iii) compare outcomes between children identified via well-established UNHS and the general population. METHODS: Linear regression adjusted for potential confounding factors was used throughout. Via a quasi-experimental design, language and psychosocial outcomes were compared across four population-based Australian systems of hearing loss detection: opportunistic detection, born 1991-1993, n = 50; universal risk factor referral, born 2003-2005, n = 34; newly established UNHS, born 2003-2005, n = 41; and well-established UNHS, born 2007-2010, n = 21. In pooled analyses, we examined whether age of detection predicted outcomes. Outcomes were similarly compared between the current well-established UNHS system and typically developing children in the Early Language in Victoria Study, born 2003, n = 1217. RESULTS: Age at diagnosis and hearing aid fitting fell steadily across the four systems. For moderate losses, mean expressive language (P for trend .05) and receptive vocabulary (P for trend .06) improved across the four systems, but benefit was not obvious for mild losses. In pooled analyses, diagnosis before age six months predicted better language outcomes for moderate losses. Children with mild-moderate losses exposed to well-established UNHS continue to experience expressive language scores well below children in the general population (adjusted mean difference -8.9 points, 95% CI -14.7 to -3.1). CONCLUSIONS: Treatment arising from UNHS appears to be clearly benefitting children with moderate hearing losses. However, rigorous trials are needed to quantify benefits, versus costs and potential harms, of early aiding of children with mild losses.
Assuntos
Auxiliares de Audição , Perda Auditiva/diagnóstico , Perda Auditiva/terapia , Austrália , Criança , Análise Custo-Benefício , Feminino , Auxiliares de Audição/efeitos adversos , Auxiliares de Audição/economia , Perda Auditiva/economia , Perda Auditiva/fisiopatologia , Testes Auditivos , Humanos , Idioma , Desenvolvimento da Linguagem , Modelos Lineares , Estudos Longitudinais , Masculino , Pessoas com Deficiência Auditiva , Avaliação de Programas e Projetos de Saúde , Ajuste de Prótese/efeitos adversos , Ajuste de Prótese/métodos , Qualidade de Vida , Fatores de Risco , Percepção da FalaRESUMO
BACKGROUND AND PURPOSE: Diffusion and fMRI has been providing insights to brain development in addition to anatomic imaging. This study aimed to evaluate the microstructure of white matter tracts underlying the default mode network in premature infants by using resting-state functional MR imaging in conjunction with diffusion tensor imaging-based tractography. MATERIALS AND METHODS: A cohort of 44 preterm infants underwent structural T1-weighted imaging, resting-state fMRI, and DTI at 3T, including 21 infants with brain injuries and 23 infants with normal-appearing structural imaging as controls. Neurodevelopment was evaluated with the Bayley Scales of Infant Development at 12 months' adjusted age. Probabilistic independent component analysis was applied to resting-state fMRI data to explore resting-state networks. The localized clusters of the default mode network were used as seeding for probabilistic tractography. The DTI metrics (fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity) of the reconstructed primary tracts within the default mode network-cingula were measured. RESULTS: Results revealed decreased fractional anisotropy (0.20 ± 0.03) and elevated radial diffusivity values (1.24 ± 0.16) of the cingula in the preterm infants with brain injuries compared with controls (fractional anisotropy, 0.25 ± 0.03; P < .001; radial diffusivity, 1.06 ± 0.16; P = .001). The Bayley Scales of Infant Development cognitive scores were significantly associated with cingulate fractional anisotropy (P = .004) and radial diffusivity (P = .021); this association suggests that the microstructural properties of interconnecting axonal pathways within the default mode network are of critical importance in the early neurocognitive development of infants. CONCLUSIONS: This study of combined resting-state fMRI and DTI at rest suggests that such studies may allow the investigation of key functional brain circuits in premature infants, which could function not only as diagnostic tools but also as biomarkers for long-term neurodevelopmental outcomes.
Assuntos
Mapeamento Encefálico/métodos , Encéfalo/diagnóstico por imagem , Imagem de Tensor de Difusão/métodos , Recém-Nascido Prematuro/crescimento & desenvolvimento , Imageamento por Ressonância Magnética/métodos , Anisotropia , Encéfalo/crescimento & desenvolvimento , Feminino , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro/fisiologia , Masculino , Substância Branca/diagnóstico por imagem , Substância Branca/crescimento & desenvolvimentoRESUMO
Previous studies of the stoichiometry of thiosulfate oxidation by colorless sulfur bacteria have failed to demonstrate mass balance of sulfur, indicating that unidentified oxidized products must be present. Here the reaction stoichiometry and kinetics under variable pH conditions during the growth of Thiomicrospira thermophila strain EPR85, isolated from diffuse hydrothermal fluids at the East Pacific Rise, is presented. At pH 8.0, thiosulfate was stoichiometrically converted to sulfate. At lower pH, the products of thiosulfate oxidation were extracellular elemental sulfur and sulfate. We were able to replicate previous experiments and identify the missing sulfur as tetrathionate, consistent with previous reports of the activity of thiosulfate dehydrogenase. Tetrathionate was formed under slightly acidic conditions. Genomic DNA from T. thermophila strain EPR85 contains genes homologous to those in the Sox pathway (soxAXYZBCDL), as well as rhodanese and thiosulfate dehydrogenase. No other sulfur oxidizing bacteria containing sox(CD)2 genes have been reported to produce extracellular elemental sulfur. If the apparent modified Sox pathway we observed in T. thermophila is present in marine Thiobacillus and Thiomicrospira species, production of extracellular elemental sulfur may be biogeochemically important in marine sulfur cycling.
Assuntos
Thiobacillus/metabolismo , Tiossulfatos/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Oxirredução , Óxidos/metabolismo , Oxirredutases/genética , Oxirredutases/metabolismo , Enxofre/metabolismo , Compostos de Enxofre/metabolismo , Thiobacillus/enzimologia , Thiobacillus/genéticaRESUMO
OBJECTIVES: The aim of this study was to investigate and compare auditory brainstem response (ABR) thresholds related to otitis media with effusion (OME) in infants with and without cleft palate and/or lip (CP±L). METHODS: Forty-seven infants with CP±L and 67 infants with OME participated in the study. Hearing thresholds of ears of infants with OME were compared between groups and within the group with CP±L. RESULTS: Infants with CP±L and OME presented with similar hearing thresholds as infants with OME and not CP±L. Within the cleft group, infants with isolated cleft palate and OME demonstrated significantly higher hearing thresholds than infants with unilateral cleft lip and palate and OME. CONCLUSION: A high prevalence of infants with CP±L present with OME early in life. Hearing thresholds of these infants are similar to infants without CP±L, but with OME. The ear status and hearing thresholds of infants with CP±L needs to be monitored to be able to provide the best access to hearing in order to fully allow speech and language development.
Assuntos
Fenda Labial/fisiopatologia , Fissura Palatina/fisiopatologia , Potenciais Evocados Auditivos do Tronco Encefálico/fisiologia , Perda Auditiva/epidemiologia , Otite Média com Derrame/fisiopatologia , Feminino , Audição , Perda Auditiva/etiologia , Testes Auditivos , Humanos , Lactente , Masculino , Prevalência , Estudos RetrospectivosRESUMO
The metastatic spread of cancer cells to distant sites represents the major cause of cancer-related deaths in breast cancer patients, and lungs are one of the most common sites for metastatic colonization. Developing a physiologically relevant tissue culture model to mimic lung colonization of breast cancer is crucial for the investigation of the biology of cancer metastasis and evaluation of drug treatment efficacy. Here, we describe an ex vivo lung colonization assay for breast cancer using the native three-dimensional (3D) lung extracellular matrix. The native matrix was isolated from murine lungs using a decellularization technique, and the preservation of extracellular matrix (ECM) composition, integrity and mechanical properties was confirmed. We showed that metastatic MDA-MB 231 and 4T1 cells invaded and colonized in the decellularized lung matrix, whereas only a small mass of non-metastatic MCF7 cells survived under the same condition. Furthermore, knockdown of ZEB1, an epithelial-mesenchymal transition (EMT) inducer, significantly reduced invasion and colonization of MDA-MB 231 cells in the decellularized lung, suggesting an important role of EMT in breast cancer metastasis. We conclude that the decellularized lung retains the biophysical and biochemical properties of the lung ECM and provides a powerful tool to investigate the lung colonization of breast cancer.
Assuntos
Neoplasias da Mama , Neoplasias Pulmonares/secundário , Modelos Biológicos , Animais , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Transição Epitelial-Mesenquimal , Matriz Extracelular/patologia , Feminino , Humanos , Neoplasias Pulmonares/patologia , Células MCF-7 , Camundongos , Invasividade NeoplásicaRESUMO
A consensus clinical reasoning framework for best practice for the examination of the cervical spine region has been developed through an iterative consultative process with experts and manual physical therapy organisations. The framework was approved by the 22 member countries of the International Federation of Orthopaedic Manipulative Physical Therapists (October 2012). The purpose of the framework is to provide guidance to clinicians for the assessment of the cervical region for potential of Cervical Arterial Dysfunction in advance of planned management (inclusive of manual therapy and exercise interventions). The best, most recent scientific evidence is combined with international expert opinion, and is presented with the intention to be informative, but not prescriptive; and therefore as an aid to the clinician's clinical reasoning. Important underlying principles of the framework are that 1] although presentations and adverse events of Cervical Arterial Dysfunction are rare, it is a potentially serious condition and needs to be considered in musculoskeletal assessment; 2] manual therapists cannot rely on the results of one clinical test to draw conclusions as to the presence or risk of Cervical Arterial Dysfunction; and 3] a clinically reasoned understanding of the patient's presentation, including a risk:benefit analysis, following an informed, planned and individualised assessment, is essential for recognition of this condition and for safe manual therapy practice in the cervical region. Clinicians should also be cognisant of jurisdictionally specific requirements and obligations, particularly related to patient informed consent, when intending to use manual therapy in the cervical region.
Assuntos
Doenças das Artérias Carótidas/diagnóstico , Vértebras Cervicais/irrigação sanguínea , Manipulação da Coluna/métodos , Cervicalgia/reabilitação , Exame Físico/métodos , Insuficiência Vertebrobasilar/diagnóstico , Doenças das Artérias Carótidas/epidemiologia , Vértebras Cervicais/fisiopatologia , Consenso , Feminino , Seguimentos , Humanos , Internacionalidade , Instabilidade Articular/diagnóstico , Instabilidade Articular/reabilitação , Masculino , Manipulação da Coluna/efeitos adversos , Anamnese , Manipulações Musculoesqueléticas/efeitos adversos , Manipulações Musculoesqueléticas/métodos , Cervicalgia/diagnóstico , Segurança do Paciente , Guias de Prática Clínica como Assunto , Medição de Risco , Resultado do Tratamento , Insuficiência Vertebrobasilar/epidemiologiaRESUMO
While the most common presentation of actinomycosis is cervicofacial disease, or "lumpy jaw syndrome," Actinomyces meyeri has a predilection for pulmonary disease as well as dissemination to distant organs. We describe a 61-year-old Caucasian male with a relapsing-remitting mandibular sinus tract who would go on to develop weight loss, dyspnea, and a cough productive of malodorous sputum. Imaging revealed a right lower lobe pneumonia and a large left sided empyema. He underwent thoracotomy and decortication on the left side, and 1 L of foul-smelling purulent fluid was drained. Culture grew Actinomyces meyeri. He completed an extended antibiotic course and had his teeth extracted with good clinical outcome.
Assuntos
Actinomyces/isolamento & purificação , Actinomicose/microbiologia , Empiema/microbiologia , Doenças Maxilomandibulares/microbiologia , Pneumonia Bacteriana/microbiologia , Humanos , Masculino , Pessoa de Meia-Idade , Extração DentáriaRESUMO
OBJECTIVES: To assess the applicability of the newly developed ICECAP-O capability index in the measurement and valuation of quality of life in a large community based sample of the Australian general population. With origins in Sen's capability theory, the ICECAP-O may more fully encapsulate the multi-dimensional outcomes of public health policies and interventions than traditional health economic constructs. METHODS: 2,937 Australian residents participated in face-to-face interviews. The relationships between ICECAP-O scores according to age groups (<65 or >65 years) and socio-economic status were investigated using descriptive statistics and multivariable linear regression models. RESULTS: Lower income levels and being unemployed or physically unable to work were negatively associated with capability for both age groups. Capability was strongly and positively associated with marriage and cohabitation in the younger age group, whilst being Australian-born was a positive indicator for the older group. CONCLUSIONS: The results provide insights into the assessment of capability in the Australian general population. The ICECAP-O shows promise for application in the measurement and valuation of quality of life in general population surveys, and incorporation into economic evaluations of public health interventions.
Assuntos
Saúde Pública , Qualidade de Vida , Valores Sociais , Inquéritos e Questionários , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Inquéritos Epidemiológicos/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Vigilância da População , Pesquisa Qualitativa , Anos de Vida Ajustados por Qualidade de Vida , Classe Social , Austrália do Sul , Adulto JovemRESUMO
OBJECTIVE: The aim of this study was to develop a measure of social care outcome, an equivalent to the quality-adjusted life year (QALY) in health, which could be used in a range of circumstances. DESIGN: The project drew on previous and parallel work developing the Adult Social Care Outcome Toolkit and the national Adult Social Care Survey. We developed and tested an instrument designed to reflect service users' social care-related quality of life (SCRQoL) and tested it with 30 service users from a variety of user groups and 300 older home care service users. In parallel, we explored discrete choice experiment (DCE) and best-worst scaling (BWS) approaches to preference elicitation with 300 members of the general population, and cognitively tested these with service users. We also cognitively tested a computer-aided time trade-off (TTO) exercise using SCRQoL attributes with members of the general population. In the second phase, using the finalised instruments, BWS interviews were conducted with 500 members of the general population, TTO interviews with a follow-up sample of 126 of these respondents, and BWS interviews with 458 people using equipment services. MAIN OUTCOME MEASURES: The final measure had eight domains: personal cleanliness and comfort, accommodation cleanliness and comfort, food and drink, safety, social participation and involvement, occupation, control over daily life and dignity. In addition to measuring current SCRQoL, the instrument includes questions used to establish service users' views of their 'expected' SCRQoL in the absence of services. The difference between a person's current and 'expected' SCRQoL provides an indicator of service impact. RESULTS: There was good evidence for the validity of the descriptive system and the validity of the current, expected and SCRQoL gain scales. The DCE and BWS approaches yielded similar results and, once introductions made clear, were understood by service users. BWS was used for the main stages, as it had technical and cognitive advantages. The computer-aided approach to TTO worked well, and respondents found questions acceptable and understandable. There were no substantive differences in the preferences of service users and the general population. The key domain was control over daily life, with the lowest and highest levels strongly estimated in all models. After allowing for observable heterogeneity, service users' preferences appeared to be more closely associated with their own SCRQoL than with those of the general population. The consistency of the results with the results of a previous study allowed the final model to be based on the preferences of 1000 members of the general population. A formula based on the relationship between TTO and BWS values was estimated for a social care QALY, with '0' equivalent to 'being dead' and '1' being the 'ideal' SCRQoL state. Members of the population experienced significantly higher SCRQoL than service users. CONCLUSIONS: Although further work is needed, particularly to develop an equivalent measure for informal carers and to explore the links with health QALYs, the measure has considerable potential. A number of methodological advances were achieved, including the first application of TTO in a social care context and use of BWS to establish service user preferences. FUNDING: The National Institute for Health Research Health Technology Assessment programme.
Assuntos
Recursos em Saúde , Avaliação de Resultados em Cuidados de Saúde/métodos , Qualidade da Assistência à Saúde , Anos de Vida Ajustados por Qualidade de Vida , Serviço Social/organização & administração , Idoso , Idoso de 80 Anos ou mais , Inglaterra , Feminino , Humanos , Modelos Lineares , Masculino , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Satisfação do Paciente , Psicometria , Qualidade de Vida , Serviço Social/estatística & dados numéricos , Estatística como AssuntoRESUMO
The aim of this study was to explore whether intellectual performance in children with Sickle Cell Disease and with low risk of stroke as determined with conventional transcranial Doppler ultrasonography (TCD) criteria was associated with hemodynamic parameters in imaging TCD, when controlling for hematological and socio-economical variables and presence of silent infarcts. We performed neuropsychological testing with Kaufman Brief Intelligence Test (K-BIT-IQ) and imaging TCD examinations to measure blood flow velocities and pulsatility indexes (PI) in the middle cerebral arteries (MCA) In 46 children with homozygous HbSS (mean age 108±34 months, range limits: 47-166 months; 24 females), without a history of stroke or transient ischemic attack, with no stenosis on magnetic resonance angiography and with velocities below 170 cm/s in screening conventional TCD. Mean K-BIT IQ Composite and Vocabulary scores (91±13 and 86±14 respectively) were significantly below the average scores of 100 for the age-matched population (one sample t-test=5.21, p<0.001). Using univariate and multivariate regression models, we found that lower PI in the right MCA was associated with lower K-BIT-IQ Composite and Vocabulary scores. Furthermore, we found that interhemispheric differences in PIs were even more strongly associated with neuropsychological performance, whereas flow velocities were not associated with the K-BIT-IQ score. Using a model of chronic anemia, we found that cognitive functioning was associated with cerebral hemodynamics.
RESUMO
INTRODUCTION: Perioperative allergic conjunctivitis accelerates the speed of corneal allograft rejection. This study examines the effect of allergic conjunctivitis, with and without dexamethasone treatment, on the early inflammatory response and lymphangiogenesis in the host cornea following corneal transplantation. METHODS: Allogeneic fully MHC-mismatched C57Bl/6 strain donor corneas were transplanted into naive A/J mice and into A/J mice with active allergic conjunctivitis. Further groups of allograft recipients with allergic conjunctivitis were treated post-operatively with twice daily topical dexamethasone 0.1% or phosphate-buffered saline. Mice were killed on days 2 and 6 and corneas were examined by (i) fluorescent immunohistochemistry of frozen sections using anti-CD11b, anti-F4/80 and anti-Gr-1 antibodies, or (ii) whole-mount staining with anti-LYVE-1 antibody. Lymphatic ingrowth and numbers of cells infiltrating the host cornea were compared between groups. RESULTS: There were significantly higher numbers of CD11b(+) cells and LYVE-1(+) vessels in the host cornea at day 2 in allergic compared with naive recipients, but no differences between naive and allergic recipients at day 6. In allergic eyes, dexamethasone treatment significantly inhibited LYVE-1 expression at days 2 and 6, and significantly improved allograft survival in recipients with allergic conjunctivitis if maintained for a week. CONCLUSIONS: The innate immune response to allogeneic corneal tissue is more vigorous in the presence of allergic conjunctivitis than in naive eyes and is associated with accelerated lymphatic ingrowth to host cornea. Topical dexamethasone inhibits lymphatic ingrowth and this may be one mechanism by which topical steroid enhances graft survival.
Assuntos
Conjuntivite Alérgica/imunologia , Córnea/imunologia , Transplante de Córnea , Linfangiogênese/fisiologia , Vasos Linfáticos/imunologia , Animais , Antígenos de Diferenciação/metabolismo , Antígeno CD11b/metabolismo , Conjuntivite Alérgica/tratamento farmacológico , Dexametasona/uso terapêutico , Feminino , Técnica Indireta de Fluorescência para Anticorpo , Glucocorticoides/uso terapêutico , Glicoproteínas/imunologia , Sobrevivência de Enxerto , Linfangiogênese/efeitos dos fármacos , Vasos Linfáticos/efeitos dos fármacos , Proteínas de Membrana Transportadoras , Camundongos , Camundongos Endogâmicos A , Camundongos Endogâmicos C57BL , Período Perioperatório , Receptores de Quimiocinas/imunologiaRESUMO
BACKGROUND/AIMS: Diagnosis of rejection in the mouse model of corneal transplantation is based on subjective judgement of loss of graft transparency. The aims of this study were to (1) evaluate a pachymetry technique to measure changes in mouse corneal thickness and (2) correlate increases in transplant thickness with clinical and histological features of rejection. METHODS: Orthotopic corneal allografts (C57BL/6 strain donor) and syngeneic grafts were performed in A/J mice. Graft transparency was graded and corneal thickness measured by pachymetry on alternate days. Transverse sections of donor cornea excised from eyes representative of clinical opacity grades 1-4 were prepared, photographed, graft section thickness measured and stromal graft-infiltrating cells counted. Intraobserver and interobserver variations in pachymetry were statistically tested. RESULTS: Graft thickness, as measured by pachymetry, increased with each clinical opacity grade. Thickness for opacity grades 0, 1 and 2 was less than 300 microm in all recipients. Graft thickness for grades 3 and 4 was greater than 300 microm in all cases. For measurements up to 400 mum, there was a good correlation between thickness as measured by in vivo pachymetry and in histopathological sections. The mean interobserver bias was -11.35 microm, while the mean intraobserver bias was +3.96 microm. Stromal cellularity increased with increasing corneal thickness up to approximately 300 microm. CONCLUSION: In vivo graft pachymetry provides a new and reliable way to objectively diagnose rejection in the mouse model of corneal transplantation.
Assuntos
Transplante de Córnea , Rejeição de Enxerto/diagnóstico por imagem , Animais , Córnea/patologia , Substância Própria/patologia , Topografia da Córnea/métodos , Criopreservação , Técnicas de Diagnóstico Oftalmológico , Modelos Animais de Doenças , Feminino , Rejeição de Enxerto/patologia , Camundongos , Camundongos Endogâmicos A , Camundongos Endogâmicos C57BL , Reprodutibilidade dos Testes , Índice de Gravidade de Doença , UltrassonografiaRESUMO
As biopsies are not taken at the time of human corneal allograft rejection, most information on the early cellular changes in rejection is from animal models. We examined the phenotype of alloreactive cells present in the human anterior chamber during corneal graft rejection by flow cytometry and quantified aqueous humor levels of cytokines and chemokines using cytometric bead array. Aqueous and peripheral blood samples were taken from patients with graft endothelial rejection (n = 11) and from control patients undergoing cataract surgery (n = 8). CD45(+)CD4(+), CD45(+)CD8(+) and CD45(+)CD14(+) cells were found in aqueous during rejection; no CD45(+) cells were seen in control samples. Higher proportions of CD45(+) cells found in aqueous during rejection were CD14(+), denoting monocyte/macrophage lineage, than were CD4(+) or CD8(+). Large elevations were seen in aqueous levels of IL-6, MCP-1 and IP-10 during rejection compared with controls; smaller but still statistically significant increases were seen in MIP-1alpha and eotaxin. The role of CD14(+) cells in allorejection is unclear as is the potential of these chemokines and their receptors as therapeutic targets. Aqueous humor samples offer a unique opportunity to analyze components of the allogeneic response in direct contact with donor tissue but without artifacts inherent in examination of tissue.
Assuntos
Humor Aquoso/imunologia , Quimiocinas/análise , Citocinas/análise , Rejeição de Enxerto/imunologia , Idoso , Idoso de 80 Anos ou mais , Antígenos CD4/análise , Antígenos CD8/análise , Estudos de Casos e Controles , Quimiocina CCL2/análise , Quimiocina CXCL10/análise , Quimiocinas/imunologia , Transplante de Córnea , Citocinas/imunologia , Feminino , Citometria de Fluxo , Humanos , Interleucina-6/análise , Antígenos Comuns de Leucócito/análise , Receptores de Lipopolissacarídeos/análise , Masculino , Pessoa de Meia-Idade , FenótipoRESUMO
Magnetoencephalography (MEG) is increasingly being used in the preoperative evaluation of pediatric patients with epilepsy. The ability to noninvasively localize ictal onset zones (IOZ) and their relationships to eloquent functional cortex allows the pediatric epilepsy team to more accurately assess the likelihood of postoperative seizure freedom, while more precisely prognosticating the potential functional deficits that may be expected from resective surgery. Confirmation of clinically suggested multifocality may result in a recommendation against resective surgery because the probability of seizure freedom will be low. Current paradigms for motor and somatosensory testing are robust. Paradigms allowing localization of those regions necessary for competent language function, though promising, are under continuous optimization. MR imaging white matter trajectory data, created from diffusion tensor imaging obtained in the same setting as the localization brain MR imaging, provide ancillary information regarding connectivity of the IOZ to sites of rapid secondary spread and the spatial relationship of the IOZ to functionally important white matter bundles, such as the corticospinal tracts. A collaborative effort between neuroradiology, neurology, neurosurgery, neuropsychology, technology, and physics ensures successful implementation of MEG within a pediatric epilepsy program.