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1.
J Chem Phys ; 148(5): 054310, 2018 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-29421878

RESUMO

This work presents the analysis of non-equilibrium energy transfer and dissociation of nitrogen molecules (N2(Σg+1)) using two different approaches: the direct molecular simulation (DMS) method and the coarse-grain quasi-classical trajectory (CG-QCT) method. The two methods are used to study thermochemical relaxation in a zero-dimensional isochoric and isothermal reactor in which the nitrogen molecules are heated to several thousand degrees Kelvin, forcing the system into strong non-equilibrium. The analysis considers thermochemical relaxation for temperatures ranging from 10 000 to 25 000 K. Both methods make use of the same potential energy surface for the N2(Σg+1)-N2(Σg+1) system taken from the NASA Ames quantum chemistry database. Within the CG-QCT method, the rovibrational energy levels of the electronic ground state of the nitrogen molecule are lumped into a reduced number of bins. Two different grouping strategies are used: the more conventional vibrational-based grouping, widely used in the literature, and energy-based grouping. The analysis of both the internal state populations and concentration profiles show excellent agreement between the energy-based grouping and the DMS solutions. During the energy transfer process, discrepancies arise between the energy-based grouping and DMS solution due to the increased importance of mode separation for low energy states. By contrast, the vibrational grouping, traditionally considered state-of-the-art, captures well the behavior of the energy relaxation but fails to consistently predict the dissociation process. The deficiency of the vibrational grouping model is due to the assumption of strict mode separation and equilibrium of rotational energy states. These assumptions result in errors predicting the energy contribution to dissociation from the rotational and vibrational modes, with rotational energy actually contributing 30%-40% of the energy required to dissociate a molecule. This work confirms the findings discussed in Paper I [R. L. Macdonald et al., J. Chem. Phys. 148, 054309 (2018)], which underlines the importance of rotational energy to the dissociation process, and demonstrates that an accurate non-equilibrium chemistry model must accurately predict the deviation of rovibrational distribution from equilibrium.

2.
Osteoporos Int ; 24(8): 2253-9, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23443412

RESUMO

UNLABELLED: To achieve an efficient molecular diagnosis of osteogenesis imperfecta (OI), Ehlers-Danlos syndrome (EDS), and osteopetrosis (OPT), we designed a next-generation sequencing (NGS) platform to sequence 34 genes. We validated this platform on known cases and have successfully identified the causative mutation in most patients without a prior molecular diagnosis. INTRODUCTION: Osteogenesis imperfecta, Ehlers-Danlos syndrome, and osteopetrosis are collectively common inherited skeletal diseases. Evaluation of subjects with these conditions often includes molecular testing which has important counseling and therapeutic and sometimes legal implications. Since several different genes have been implicated in these conditions, Sanger sequencing of each gene can be a prohibitively expensive and time-consuming way to reach a molecular diagnosis. METHODS: In order to circumvent these problems, we have designed and tested a NGS platform that would allow simultaneous sequencing on a single diagnostic platform of different genes implicated in OI, OPT, EDS, and other inherited conditions, leading to low or high bone mineral density. We used a liquid-phase probe library that captures 602 exons (~100 kb) of 34 selected genes and have applied it to test clinical samples from patients with bone disorders. RESULTS: NGS of the captured exons by Illumina HiSeq 2000 resulted in an average coverage of over 900X. The platform was successfully validated by identifying mutations in six patients with known mutations. Moreover, in four patients with OI or OPT without a prior molecular diagnosis, the assay was able to detect the causative mutations. CONCLUSIONS: In conclusion, our NGS panel provides a fast and accurate method to arrive at a molecular diagnosis in most patients with inherited high or low bone mineral density disorders.


Assuntos
Densidade Óssea/genética , Doenças do Desenvolvimento Ósseo/diagnóstico , Doenças do Desenvolvimento Ósseo/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Adulto , Doenças do Desenvolvimento Ósseo/fisiopatologia , Síndrome de Ehlers-Danlos/diagnóstico , Síndrome de Ehlers-Danlos/genética , Síndrome de Ehlers-Danlos/fisiopatologia , Biblioteca Gênica , Predisposição Genética para Doença , Testes Genéticos/métodos , Humanos , Masculino , Mutação , Osteogênese Imperfeita/diagnóstico , Osteogênese Imperfeita/genética , Osteogênese Imperfeita/fisiopatologia , Osteopetrose/diagnóstico , Osteopetrose/genética , Osteopetrose/fisiopatologia , Análise de Sequência de DNA/métodos
3.
J Laryngol Otol ; 136(12): 1296-1303, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35791976

RESUMO

OBJECTIVE: To study unusual presentations of coronavirus-associated mucormycosis that are rarely seen in sinonasal mucormycosis cases. METHOD: The data of 400 rhino-orbito-cerebral mucormycosis patients admitted to Sawai Man Singh Hospital, Jaipur, from May 2021 to June 2021, were retrospectively collected. The diagnosis of mucormycosis was made by histological examination of biopsy samples. RESULTS: Out of 400 patients, 62 had symptoms other than common symptoms of rhino-orbito-cerebral mucormycosis. Thirty-four patients had facial palsy, 19 complained of gum ulcers, 6 developed a cheek abscess, 2 complained of maggots in the nose along with common rhino-orbito-cerebral mucormycosis symptoms, and 1 had a cerebellar infarct. CONCLUSION: Mucormycosis is a disease with various presentations, and coronavirus-associated mucormycosis has added unusual presentations to the existing list of manifestations of rhino-orbito-cerebral mucormycosis. In this coronavirus disease era, mucormycosis should always be considered as a diagnosis in patients with these unusual presentations.


Assuntos
Coronavirus , Mucormicose , Doenças Orbitárias , Humanos , Masculino , Mucormicose/complicações , Mucormicose/diagnóstico , Estudos Retrospectivos
4.
Psychol Med ; 41(12): 2581-91, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21733215

RESUMO

BACKGROUND: Anorexia nervosa (AN) poses a major burden on families. Carers (e.g. parents or partners) of people with AN are often highly distressed and may inadvertently respond in ways that can contribute to the maintenance of the disorder, e.g. through high levels of over-involvement and criticism [also known as expressed emotion (EE)]. This study aimed to evaluate the efficacy of a novel web-based systemic cognitive-behavioural (CBT) intervention for carers of people with AN, designed to reduce carer distress and teach skills in how to offer effective support. METHOD: Carers of people with AN (n=64) were randomly allocated to either the web-intervention, overcoming anorexia online, with limited clinician supportive guidance (by email or phone), or to ad-hoc usual support from the UK patient and carer organization Beat. Carer outcomes were assessed at post-treatment (4 months) and follow-up (6 months). RESULTS: Compared with the control intervention, web-based treatment significantly reduced carers' anxiety and depression (primary outcome) at post-treatment, with a similar trend in carers' EE. Other secondary outcomes did not favour the online intervention. Gains were maintained at follow-up. CONCLUSIONS: This is the first ever study to use an online CBT program to successfully reduce carer distress and improve carers' ability to support the person with AN.


Assuntos
Anorexia Nervosa/terapia , Cuidadores/educação , Terapia Cognitivo-Comportamental/métodos , Instrução por Computador , Adulto , Anorexia Nervosa/psicologia , Ansiedade/prevenção & controle , Cuidadores/psicologia , Depressão/prevenção & controle , Feminino , Humanos , Internet , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Estresse Psicológico/prevenção & controle , Inquéritos e Questionários , Adulto Jovem
5.
J Laryngol Otol ; 135(5): 442-447, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33827722

RESUMO

OBJECTIVE: To study the possible association between invasive fungal sinusitis (mucormycosis) and coronavirus disease. METHODS: A prospective observational study was conducted at a tertiary care centre over four months, involving all patients with mucormycosis of the paranasal sinuses suffering from or having a history of coronavirus disease infection. RESULTS: Twenty-three patients presented with mucormycosis, all had an association with coronavirus disease 2019. The ethmoids (100 per cent) were the most common sinuses affected. Intra-orbital extension was seen in 43.47 per cent of cases, while intracranial extension was only seen in 8.69 per cent. Diabetes mellitus was present in 21 of 23 cases, and was uncontrolled in 12 cases. All patients had a history of steroid use during their coronavirus treatment. CONCLUSION: New manifestations of coronavirus disease 2019 are appearing over time. The association between coronavirus and mucormycosis of the paranasal sinuses must be given serious consideration. Uncontrolled diabetes and over-zealous use of steroids are two main factors aggravating the illness, and both of these must be properly checked.


Assuntos
COVID-19/microbiologia , Mucorales/isolamento & purificação , Mucormicose/microbiologia , Seios Paranasais/microbiologia , Administração Intravenosa , Antifúngicos/administração & dosagem , Antifúngicos/uso terapêutico , COVID-19/complicações , COVID-19/diagnóstico , COVID-19/virologia , Diabetes Mellitus/epidemiologia , Feminino , Humanos , Índia/epidemiologia , Infecções Fúngicas Invasivas/diagnóstico , Infecções Fúngicas Invasivas/epidemiologia , Infecções Fúngicas Invasivas/microbiologia , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Mucorales/efeitos dos fármacos , Mucormicose/diagnóstico , Mucormicose/tratamento farmacológico , Mucormicose/etiologia , Pandemias , Seios Paranasais/diagnóstico por imagem , Estudos Prospectivos , SARS-CoV-2 , Sinusite/diagnóstico , Sinusite/microbiologia , Esteroides/efeitos adversos , Esteroides/uso terapêutico
6.
Cells Tissues Organs ; 191(1): 12-20, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-19546516

RESUMO

The production of engineered cartilage from mesenchymal stem cells is a rapidly developing field. Potential applications include the treatment of degenerative joint disease as well as the treatment of traumatic and surgical bone injury. Prior to clinical application, however, further characterization of the morphology, ultrastructure, biocompatibility, and performance of the engineered tissue is warranted. To achieve this, human mesenchymal stem cells (hMSCs) were grown in vitro in pellet culture for 3 weeks in chondrogenic medium conditions. The resultant engineered cartilage was compared to native adult and fetal tissue. Routine histology, special stains, and ultrastructural and quantitative histomorphometric analyses were performed. The engineered tissue demonstrated a similar chondrocyte phenotype, collagen fibril appearance, and matrix distribution when compared to native cartilage. By histomorphometric analysis, the cell density of the engineered cartilage was between that of native fetal and adult cartilage. The cell-to-matrix ratio and cellular area fraction of engineered cartilage samples was significantly greater than in adult samples, but indistinguishable from fetal cartilage samples, supporting the hypothesis that hMSC-engineered cartilage regeneration may mimic fetal cartilage development.


Assuntos
Cartilagem/fisiologia , Condrócitos/fisiologia , Condrogênese/fisiologia , Matriz Extracelular/fisiologia , Colágenos Fibrilares/fisiologia , Células-Tronco Mesenquimais/fisiologia , Engenharia Tecidual , Adulto , Células da Medula Óssea/citologia , Cartilagem/citologia , Cartilagem/ultraestrutura , Contagem de Células , Condrócitos/citologia , Condrócitos/ultraestrutura , Matriz Extracelular/ultraestrutura , Feto/citologia , Humanos , Células-Tronco Mesenquimais/citologia , Regeneração
7.
J Laryngol Otol ; 133(5): 368-375, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31064425

RESUMO

OBJECTIVE: To propose a new classification of inner-ear anomalies that is more clinically oriented and surgically relevant: the SMS (Sawai Man Singh) classification of cochleovestibular malformations. METHODS: A retrospective multicentric study was conducted of 436 cochlear implantations carried out in 3 Indian tertiary care institutes. Patients with anomalous anatomy were included and classified, as per the new SMS classification, into cochleovestibular malformation types I, II, III and IV, based on cochlear morphology, modiolus and lamina cribrosa. RESULTS: There were 19, 23, 8 and 4 patients with cochleovestibular malformation types I, II, III and IV, respectively. Two-year post-operative Meaningful Auditory Integration Scale scores were statistically analysed. CONCLUSION: This new classification for inner-ear anomalies is a simpler, more practical, outcome-oriented classification that can be used to better plan the surgery. These merits make it a more uniform classification for recording results.


Assuntos
Tomada de Decisão Clínica/métodos , Cóclea/anormalidades , Implante Coclear/estatística & dados numéricos , Avaliação de Resultados em Cuidados de Saúde/classificação , Vestíbulo do Labirinto/anormalidades , Criança , Pré-Escolar , Feminino , Perda Auditiva Neurossensorial/congênito , Perda Auditiva Neurossensorial/diagnóstico , Perda Auditiva Neurossensorial/cirurgia , Humanos , Índia , Masculino , Estudos Retrospectivos , Centros de Atenção Terciária
8.
Br J Psychiatry ; 193(6): 493-500, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19043154

RESUMO

BACKGROUND: Cognitive-behavioural self-care is advocated as a first step in the treatment of bulimia nervosa. AIMS: To examine the effectiveness of a CD-ROM-based cognitive-behavioural intervention in bulimia nervosa and eating disorder not otherwise specified (NOS) (bulimic type) in a routine setting. METHOD: Ninety-seven people with bulimia nervosa or eating disorder NOS were randomised to either CD-ROM without support for 3 months followed by a flexible number of therapist sessions or to a 3-month waiting list followed by 15 sessions of therapist cognitive-behavioural therapy (CBT) (ISRCTN51564819). Clinical symptoms were assessed at pre-treatment, 3 months and 7 months. RESULTS: Only two-thirds of participants started treatment. Although there were significant group x time interactions for bingeing and vomiting, favouring the CD-ROM group at 3 months and the waiting-list group at 7 months, post hoc group comparisons at 3 and 7 months found no significant differences for bingeing or vomiting. CD-ROM-based delivery of this intervention, without support from a clinician, may not be the best way of exploiting its benefits.


Assuntos
Bulimia Nervosa/terapia , CD-ROM , Terapia Cognitivo-Comportamental/métodos , Autocuidado , Adulto , Bulimia Nervosa/psicologia , Terapia Cognitivo-Comportamental/instrumentação , Feminino , Seguimentos , Humanos , Masculino , Cooperação do Paciente , Autocuidado/métodos , Fatores de Tempo , Resultado do Tratamento , Listas de Espera
9.
Colorectal Dis ; 10(9): 935-42, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18294271

RESUMO

OBJECTIVE: Day case surgery is safe and offers potential benefits to both patients and healthcare providers. This study aimed to describe national changes in colorectal day case workload between 1998 and 2005. METHODS: Admission data relating to Office of Population Censuses and Surveys Classification of Surgical Operations and Procedures (4th revision) (OPCS-4) coloproctology operation codes were analysed using the Hospital Episode Statistics (HES) database. Day case rates (DCRs) were calculated as the proportion of elective cases performed on an ambulatory basis. RESULTS: In total, 3 119 058 colorectal admissions were recorded on the HES database between 1998 and 2005; 1 891 474 (61%) of these were for lower gastrointestinal endoscopies. Emergency cases accounted for 527 665 (17%), elective inpatient cases for 406 368 (13%) and elective day cases for 293 551 (9%) admissions. Throughout the study period the DCRs for five commonly performed elective colorectal procedures were: 0.70 for anal lesion excisions (OPCS-4 codes: H48.1, H48.2 and H48.3); 0.16 for haemorrhoidectomy (OPCS-4 code: H51.1); 0.63 for anal fissure procedures (OPCS-4 codes: H56.2 and H56.4); 0.39 for elective procedures for anal fistula (OPCS-4 codes: H55.1, H55.2, H55.3 and H55.4); 0.37 for elective pilonidal surgery (OPCS-4 codes: H59 and H60.2). Two emergency operations, drainage of perianal and pilonidal abscesses (OPCS-4 codes: H58.2 and H60.3 respectively), were identified as operations potentially amenable to day surgery. Over the seven study years, an annual average of 8559 (+/-SD 307) admissions were coded to drainage of a perianal abscess and 4676 (+/-SD 478) admissions to drainage of pilonidal abscess. The average annual bed usage associated with these procedures was 18 831 (+/-SD 718) and 7623 (+/-SD 436) bed days respectively. CONCLUSIONS: Colorectal day case surgery is currently under-exploited in the NHS. By lifting some of the barriers to day case surgery significant resource savings may be possible.


Assuntos
Procedimentos Cirúrgicos Ambulatórios/tendências , Procedimentos Cirúrgicos do Sistema Digestório/tendências , Programas Nacionais de Saúde/estatística & dados numéricos , Endoscopia Gastrointestinal/tendências , Hemorroidas/cirurgia , Humanos , Seio Pilonidal/cirurgia , Fístula Retal/cirurgia , Reino Unido
10.
Pathol Res Pract ; 204(2): 113-20, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-17931791

RESUMO

While reviewing the cardiac histopathology and the postmortem arteriography of patients studied at autopsy, a collection of findings was identified in a small proportion of those with ischemic heart disease. These included varying degrees of hypertrophy and left ventricular dilation and severe multifocal atherosclerotic obstruction of the coronary arteries by gross examination. Histology showed multiple small foci of coagulation or contraction-band necrosis in a circumferential, subendocardial pattern; focal replacement fibrosis of varying ages and size; focal atrophy or vacuolization (a marker of chronic ischemia) of surviving myocytes; and marked dilation of the subendocardial vasculature. This collection of findings described here is termed multifocal ischemic necroses of varying age (MINOVA). Review of patient histories showed that the clinical suspicion for the degree of ischemic heart disease did not correlate well with the severity of the pathological findings.


Assuntos
Doença da Artéria Coronariana/patologia , Vasos Coronários/patologia , Isquemia Miocárdica/patologia , Miocárdio/patologia , Idoso de 80 Anos ou mais , Autopsia , Estudos de Casos e Controles , Doença Crônica , Circulação Colateral , Angiografia Coronária , Doença da Artéria Coronariana/classificação , Doença da Artéria Coronariana/fisiopatologia , Circulação Coronária , Vasos Coronários/fisiopatologia , Dilatação Patológica , Progressão da Doença , Feminino , Fibrose , Cardiopatias , Ventrículos do Coração/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/classificação , Isquemia Miocárdica/fisiopatologia , Necrose , Índice de Gravidade de Doença , Terminologia como Assunto
11.
Pediatr Neurosurg ; 44(4): 288-95, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18480617

RESUMO

BACKGROUND: The neurological deficits of myelomeningocele (MMC) have been attributed both to a primary neurulation defect and to a secondary injury of the placode in the intrauterine environment. Since astrocytes are involved in glial scar formation after spinal cord injury, the characterization of astrocyte density along the spinal cord upstream of the MMC can be used as a surrogate marker of the extension of the injury beyond the MMC. METHODS: The curly-tail/loop-tail murine model was applied to obtain newborn mice with MMC. The astrocyte density and topography both at the MMC placode level and at the upper segments of the spinal cord was characterized by immunolabeling using the anti-glial fibrillary acidic protein antibody. This was followed by a qualitative evaluation of immunolabeled cells and morphometric analysis of the samples. RESULTS: The topography of astrocytes in the spinal cord of MMC newborn mice was compared with that of newborn control mice (without spina bifida aperta) (n = 8/group). The anti-glial fibrillary acidic protein immunoreactivity was significantly increased in the MMC samples in comparison with the normal spinal cord, indicating the presence of an astrocytic response. Increased astrocytosis was also observed in the transitional area located above the MMC. The astrocytosis decreased progressively along the MMC spinal cord until matching the pattern of the control spinal cords. This transitional area involved a segment of the spinal cord with a length of 240 microm in the newborn mouse. CONCLUSIONS: MMC newborn mice show spinal cord injury that is located upstream of the exposed placode and is characterized by proliferation of astrocytes. This finding offers further support for the hypothesis of a tethering mechanism as part of the spinal cord injury observed in MMC newborns.


Assuntos
Gliose/patologia , Meningomielocele/patologia , Medula Espinal/patologia , Animais , Animais Recém-Nascidos , Feminino , Proteína Glial Fibrilar Ácida/análise , Gliose/metabolismo , Imuno-Histoquímica , Masculino , Meningomielocele/metabolismo , Camundongos , Camundongos Mutantes , Medula Espinal/metabolismo
12.
J Laryngol Otol ; 132(6): 540-543, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30019665

RESUMO

OBJECTIVE: The study primarily aimed to calculate the orientation of the cochlea pre-operatively, using high-resolution computed tomography of the temporal bone, and predict the ease of electrode insertion. METHODS: Pre-operatively, high-resolution computed tomography scans were conducted on children scheduled for cochlear implantation, and two angles, α and ß, were calculated. The values of α and ß were then correlated with intra-operative difficulty in insertion of the electrode array. RESULTS: Ninety-six children were included in the study. Of the seven patients who had an α angle of less than 50 degrees, the surgeon experienced difficulties in electrode insertion. However, there were four patients with an α angle of more than 50 degrees for whom the surgeon also experienced difficulties in electrode insertion. In all these patients, the ß angle was more than 20 degrees. CONCLUSION: Calculation of cochlear orientation and its angle with the surgical axis (α and ß) can aid the planning of surgery, particularly with regard to the cochleostomy site and preservation of residual hearing.


Assuntos
Cóclea/diagnóstico por imagem , Implante Coclear/métodos , Perda Auditiva Neurossensorial/cirurgia , Osso Temporal/diagnóstico por imagem , Pré-Escolar , Cóclea/anatomia & histologia , Implantes Cocleares , Eletrodos Implantados , Feminino , Humanos , Lactente , Masculino , Cuidados Pré-Operatórios , Índice de Gravidade de Doença , Tomografia Computadorizada por Raios X
13.
Artigo em Inglês | MEDLINE | ID: mdl-28872760

RESUMO

BACKGROUND: Wireless motility capsule (WMC) findings are incompletely defined in suspected gastroparesis. We aimed to characterize regional WMC transit and contractility in relation to scintigraphy, etiology, and symptoms in patients undergoing gastric emptying testing. METHODS: A total of 209 patients with gastroparesis symptoms at NIDDK Gastroparesis Consortium centers underwent gastric scintigraphy and WMCs on separate days to measure regional transit and contractility. Validated questionnaires quantified symptoms. KEY RESULTS: Solid scintigraphy and liquid scintigraphy were delayed in 68.8% and 34.8% of patients; WMC gastric emptying times (GET) were delayed in 40.3% and showed 52.8% agreement with scintigraphy; 15.5% and 33.5% had delayed small bowel (SBTT) and colon transit (CTT) times. Transit was delayed in ≥2 regions in 23.3%. Rapid transit was rarely observed. Diabetics had slower GET but more rapid SBTT versus idiopathics (P ≤ .02). GET delays related to greater scintigraphic retention, slower SBTT, and fewer gastric contractions (P ≤ .04). Overall gastroparesis symptoms and nausea/vomiting, early satiety/fullness, bloating/distention, and upper abdominal pain subscores showed no relation to WMC transit. Upper and lower abdominal pain scores (P ≤ .03) were greater with increased colon contractions. Constipation correlated with slower CTT and higher colon contractions (P = .03). Diarrhea scores were higher with delayed SBTT and CTT (P ≤ .04). CONCLUSIONS & INFERENCES: Wireless motility capsules define gastric emptying delays similar but not identical to scintigraphy that are more severe in diabetics and relate to reduced gastric contractility. Extragastric transit delays occur in >40% with suspected gastroparesis. Gastroparesis symptoms show little association with WMC profiles, although lower symptoms relate to small bowel or colon abnormalities.


Assuntos
Endoscopia por Cápsula/métodos , Esvaziamento Gástrico , Gastroparesia/diagnóstico por imagem , Cintilografia , Endoscopia por Cápsula/instrumentação , Feminino , Gastroparesia/fisiopatologia , Humanos , Masculino , Pressão , Estudos Prospectivos
14.
Neuroscience ; 146(2): 833-40, 2007 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-17331652

RESUMO

To gain insight into the mechanisms that control the generation or maintenance of the characteristic bipolar morphology of cochlear spiral ganglion neurons, we have taken advantage of our recently developed procedure for culture of dissociated newborn mouse spiral ganglion. In these cultures, inclusion of the cytokine leukemia inhibitory factor (LIF) in the medium increases neuronal survival and the number of bipolar neurons. Here we tested effects of two other LIF-type cytokines (ciliary neurotrophic factor, CNTF; and human recombinant oncostatin M, hOSM) and of bone morphogenetic protein 4 (BMP4) on survival, morphology and neurite lengths of neurons in cultures of dissociated spiral ganglion. Like LIF, CNTF and hOSM increased neuronal survival and the number of surviving bipolar neurons. BMP4 also increased neuronal survival, but unlike LIF, CNTF and hOSM, increased the number of monopolar neurons and neurons with no neurites. In addition, population histograms demonstrate that the population lengths of the longer and shorter neurites of bipolar neurons were shorter in BMP4 containing cultures than in control or LIF cultures. When LIF and BMP4 were simultaneously added to the cultures, the BMP4 effects predominated. These experiments demonstrate that exposure to different environmental conditions can result in different morphologies in the surviving population of spiral ganglion neurons in culture.


Assuntos
Meios de Cultura/farmacologia , Neurônios/classificação , Neurônios/efeitos dos fármacos , Gânglio Espiral da Cóclea/citologia , Análise de Variância , Animais , Animais Recém-Nascidos , Proteína Morfogenética Óssea 4 , Proteínas Morfogenéticas Ósseas/farmacologia , Crescimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Meios de Cultura/química , Relação Dose-Resposta a Droga , Fator Inibidor de Leucemia/farmacologia , Camundongos , Neuritos/efeitos dos fármacos , Neurônios/citologia , Tubulina (Proteína)/metabolismo
15.
J Neurosurg ; 106(6 Suppl): 472-9, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17566405

RESUMO

OBJECT: Myelomeningocele (MMC) is the most severe form of spina bifida causing severe neurological deficits. Injury to the placode has been attributed to in utero aggression. In this study, glial and neuronal cell changes in both number and topography in mice with MMC were investigated during gestation. METHODS: The curly tail/loop-tail mice model of MMC was used, and fetuses were harvested using caesarean surgery at Days 14.5, 16.5, and 18.5 (full gestation at 19 days). Immunohistochemical analyses of the MMC placodes and the normal spinal cords from the control group were performed using anti-glial fibrillary acidic protein (astrocytes) and mouse anti-neuronal nuclear (neurons) antibodies. Light microscopy was used along with computer-assisted morphometric evaluation. Progressive increases in astrocytes in the spinal cord of all mouse fetuses were found between Days 14.5 and 18.5 of gestation. This increase was significantly higher in the placodes of mice with MMC than in those of normal mice, particularly in the posterior region. Neuronal labeling at Day 14.5 of gestation was similar between mice with MMC and control mice. At Day 16.5 of gestation there was a deterioration of neural tissue in MMC fetuses, mainly in the posterior region, progressing until the end of gestation with a marked loss of neurons in the entire MMC placode. CONCLUSIONS: This study delineated the quantitative changes in astrocytes and neurons associated with MMC development during the late stages of gestation. The detailed topographic analysis of the MMC defines the timing of the intrauterine insult and how the placode lesions progress. This study supports the current concept of placode protection through in utero surgery for fetuses with MMC.


Assuntos
Astrócitos/patologia , Meningomielocele/embriologia , Neurônios/patologia , Medula Espinal/embriologia , Animais , Astrócitos/metabolismo , Progressão da Doença , Embrião de Mamíferos/metabolismo , Embrião de Mamíferos/patologia , Desenvolvimento Embrionário , Feminino , Idade Gestacional , Imuno-Histoquímica/métodos , Masculino , Meningomielocele/metabolismo , Meningomielocele/patologia , Camundongos , Camundongos Mutantes , Neurônios/metabolismo , Medula Espinal/metabolismo , Medula Espinal/patologia , Coloração e Rotulagem
16.
J Bone Joint Surg Br ; 89(5): 586-90, 2007 May.
Artigo em Inglês | MEDLINE | ID: mdl-17540740

RESUMO

Metal-on-metal bearings for total hip replacement (THR) are becoming increasingly popular. Improved wear characteristics mean that these articulations are being inserted into younger patients in the form of THR and resurfacing procedures. This has led to concerns regarding potential carcinogenicity because of the increased exposure to metal ions that the procedure brings. We have studied the serum cobalt and chromium concentrations in patients who had primary, well-fixed Ring metal-on-metal THRs for more than 30 years. The levels of cobalt and chromium were elevated by five and three times, respectively compared with those in our reference groups. Metal-on-metal articulations appear to be the source of metal ions throughout the life of the prosthesis. In three patients who had undergone revision of a previous metal-on-metal THR to a metal-on-polyethylene replacement the levels of metal ions were within the normal range. The elevations of cobalt and chromium ions seen in our study were comparable with those in patients with modern metal-on-metal THRs.


Assuntos
Artroplastia de Quadril , Cromo/sangue , Cobalto/sangue , Prótese de Quadril , Adulto , Idoso , Idoso de 80 Anos ou mais , Cimentos Ósseos , Feminino , Seguimentos , Articulação do Quadril/diagnóstico por imagem , Humanos , Pessoa de Meia-Idade , Radiografia , Reoperação
18.
Chem Commun (Camb) ; 53(54): 7624-7627, 2017 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-28640293

RESUMO

Traditional methods for deriving computationally-generated collision cross sections for comparisons with ion mobility-mass spectrometry data require 3-dimensional energy-minimized structures and are often time consuming, preventing high throughput implementation. Here, we introduce a method to predict ion mobility collision cross sections of lipids and peptide analogs important in prebiotic chemistry and other fields. Using less than 100 2-D molecular descriptors this approach resulted in prediction errors of less than 2%.

19.
Artigo em Inglês | MEDLINE | ID: mdl-28066953

RESUMO

BACKGROUND: Animal studies have increasingly highlighted the role of macrophages in the development of delayed gastric emptying. However, their role in the pathophysiology of human gastroparesis is unclear. Our aim was to determine changes in macrophages and other cell types in the gastric antrum muscularis propria of patients with diabetic and idiopathic gastroparesis. METHODS: Full thickness gastric antrum biopsies were obtained from patients enrolled in the Gastroparesis Clinical Research Consortium (11 diabetic, 6 idiopathic) and 5 controls. Immunolabeling and quantitative assessment was done for interstitial cells of Cajal (ICC) (Kit), enteric nerves protein gene product 9.5, neuronal nitric oxide synthase, vasoactive intestinal peptide, substance P, tyrosine hydroxylase), overall immune cells (CD45) and anti-inflammatory macrophages (CD206). Gastric emptying was assessed using nuclear medicine scintigraphy and symptom severity using the Gastroparesis Cardinal Symptom Index. RESULTS: Both diabetic and idiopathic gastroparesis patients showed loss of ICC as compared to controls (Mean [standard error of mean]/hpf: diabetic, 2.28 [0.16]; idiopathic, 2.53 [0.47]; controls, 6.05 [0.62]; P=.004). Overall immune cell population (CD45) was unchanged but there was a loss of anti-inflammatory macrophages (CD206) in circular muscle (diabetic, 3.87 [0.32]; idiopathic, 4.16 [0.52]; controls, 6.59 [1.09]; P=.04) and myenteric plexus (diabetic, 3.83 [0.27]; idiopathic, 3.59 [0.68]; controls, 7.46 [0.51]; P=.004). There was correlation between the number of ICC and CD206-positive cells (r=.55, P=.008). Enteric nerves (PGP9.5) were unchanged: diabetic, 33.64 (3.45); idiopathic, 41.26 (6.40); controls, 46.80 (6.04). CONCLUSION: Loss of antral CD206-positive anti-inflammatory macrophages is a key feature in human gastroparesis and it is associates with ICC loss.


Assuntos
Complicações do Diabetes/metabolismo , Gastroparesia/metabolismo , Lectinas Tipo C/metabolismo , Macrófagos/metabolismo , Lectinas de Ligação a Manose/metabolismo , Antro Pilórico/metabolismo , Receptores de Superfície Celular/metabolismo , Adulto , Complicações do Diabetes/patologia , Sistema Nervoso Entérico/metabolismo , Feminino , Fibrose , Gastroparesia/patologia , Humanos , Células Intersticiais de Cajal/metabolismo , Células Intersticiais de Cajal/patologia , Masculino , Receptor de Manose , Pessoa de Meia-Idade , Antro Pilórico/patologia , Adulto Jovem
20.
Neuroscience ; 138(2): 653-62, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16413120

RESUMO

We have systematically characterized neuronal survival and growth in cultures derived from newborn/postnatal day 1 mouse cochlea. Dissociated cultures of the cochlear spiral ganglion provide an experimental environment in which to examine molecular mechanisms of survival, development and physiology of auditory neurons. To relate survival to the total number of neurons present in the source tissue, three cochleas from different newborn CD-1 mice were embedded in Araldite resin and serially sectioned at 5 mum thickness. All neurons were counted. To avoid overcounting, each section served as a lookup section for the next, giving 8240+/-423 (S.D.) neurons per ganglion. Cultures maintained in the presence of adjacent non-neural tissue, brain-derived neurotrophic factor, neurotrophin 3, leukemia inhibitory factor (LIF) and 10% fetal bovine serum returned the best overall survival (30%) at 42 h post-plating. Best overall survival required the continuous presence of a serum component(s) larger than 100,000 MW. Plating efficiency (number of neurons that attach to the well after 4 h) was similar in the presence or absence of LIF. Inclusion of LIF maintained 100% survival of plated neurons over 42 h of culture; without LIF, a large fraction of the neurons did not survive. LIF appeared to maintain survival by preferentially preserving a population of bipolar neurons, while having little effect on the number of monopolar neurons. This work provides quantitative measures of survival and morphology of auditory neurons in vitro. The results support the idea that survival of spiral ganglion neurons in vivo may depend on interactions with adjacent, non-neural tissue and raise the possibility that maintenance of bipolar morphology after hair cell damage may require biochemical mechanisms in addition to those induced by neurotrophins.


Assuntos
Vias Auditivas/anatomia & histologia , Neurônios/citologia , Gânglio Espiral da Cóclea/citologia , Animais , Animais Recém-Nascidos , Vias Auditivas/citologia , Técnicas de Cultura de Células , Sobrevivência Celular , Cóclea/citologia , Cadeias alfa de Integrinas/análise , Camundongos , Camundongos Endogâmicos
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