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2.
BMJ Open ; 9(5): e025253, 2019 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-31061024

RESUMO

OBJECTIVES: In takotsubo syndrome, QTc prolongation is a measure of risk of potentially fatal arrhythmia. It is not known how this risk, or derangement of other markers, differs across the echo variants of takotsubo syndrome. Therefore, we sought to explore whether apical takotsubo syndrome differs from the variants of the syndrome in more ways than just regional wall motion pattern. As the region of affected myocardium is usually larger, we hypothesised that patients with the classic apical ballooning form of takotsubo syndrome would have more severe derangement of their markers. DESIGN: Observational study of patients gathered from a prospective database (2010-2018) and by retrospective review (2006-2009). SETTING: The sole tertiary hospital from a New Zealand region in which case clusters of takotsubo syndrome were precipitated by large earthquakes in 2010, 2011 and 2016. PARTICIPANTS: A total of 222 patients who met a modified version of the Mayo criteria for takotsubo syndrome were included. All patients had digitally archived echocardiograms that were over-read by a second echocardiologist blinded to the clinical report. PRIMARY OUTCOME MEASURES: Ejection fraction, peak troponin and QTc interval. RESULTS: Patients with the apical form were older (p=0.011), had a lower initial left ventricular ejection fraction (35% vs 44%, p<0.0001) and a higher peak high-sensitivity troponin I (hsTnI) (p=0.01) than those with variant forms. There was no difference in the electrical abnormalities between the variants (QTc interval, heart rate, PR interval, QRS duration or T-wave axis). There was also no correlation between any of peak hsTnI, peak QTc and ejection fraction. QTc interval increased on day 2 and peaked on day 3 before falling steeply (p<0.0001). CONCLUSIONS: The variants of takotsubo syndrome differ in more ways than just their echo pattern but do not differ in their electrical abnormalities. There is a dissociation between the structural and electrical abnormalities. QTc peaks on day 3 and then falls steeply.

5.
Sci Rep ; 8(1): 7548, 2018 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-29765130

RESUMO

The pathophysiology of stress cardiomyopathy (SCM), also known as takotsubo syndrome, is poorly understood. SCM usually occurs sporadically, often in association with a stressful event, but clusters of cases are reported after major natural disasters. There is some evidence that this is a familial condition. We have examined three possible models for an underlying genetic predisposition to SCM. Our primary study cohort consists of 28 women who suffered SCM as a result of two devastating earthquakes that struck the city of Christchurch, New Zealand, in 2010 and 2011. To seek possible underlying genetic factors we carried out exome analysis, genotyping array analysis, and array comparative genomic hybridization on these subjects. The most striking finding was the observation of a markedly elevated rate of rare, heterogeneous copy number variants (CNV) of uncertain clinical significance (in 12/28 subjects). Several of these CNVs impacted on genes of cardiac relevance including RBFOX1, GPC5, KCNRG, CHODL, and GPBP1L1. There is no physical overlap between the CNVs, and the genes they impact do not appear to be functionally related. The recognition that SCM predisposition may be associated with a high rate of rare CNVs offers a novel perspective on this enigmatic condition.

8.
Methods Mol Biol ; 1493: 185-194, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-27787851

RESUMO

Rotary shadow electron microscopy (EM) of growth cone cytoskeletons provides a high-resolution method for detecting both global and macromolecular changes in cytoskeletal organization or structure. This approach can be used to study responses to repulsive guidance factors such as semaphorin 3A. Here I describe the procedures used to prepare cultured neurons for rotary-shadow EM, allowing detailed comparisons of cytoskeletal structure.


Assuntos
Cones de Crescimento/metabolismo , Microscopia Eletrônica/métodos , Semaforina-3A/metabolismo , Animais , Citoesqueleto/metabolismo , Camundongos , Neurônios/metabolismo
9.
Echocardiography ; 34(1): 122-123, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27804168

RESUMO

We document the fifth pattern of takotsubo cardiomyopathy, in which the mid-LV is hyperdynamic but the apex and base are akinetic or hypokinetic. This is a reverse mid-ventricular takotsubo. The patient is a 79-year-old woman admitted with chest pain and initially a normal EKG. Her troponin I rose to 5.4 µg/L (0.02-0.03 µg/L) and she developed QT prolongation and widespread T-wave inversion. Coronary angiography showed only very mild atheroma. Follow-up echocardiogram six weeks later showed normal left ventricular function.


Assuntos
Ecocardiografia/métodos , Ventrículos do Coração/fisiopatologia , Recuperação de Função Fisiológica , Cardiomiopatia de Takotsubo/diagnóstico , Disfunção Ventricular Esquerda/diagnóstico , Função Ventricular Esquerda/fisiologia , Idoso , Eletrocardiografia , Feminino , Seguimentos , Ventrículos do Coração/diagnóstico por imagem , Humanos , Cardiomiopatia de Takotsubo/complicações , Cardiomiopatia de Takotsubo/fisiopatologia , Disfunção Ventricular Esquerda/etiologia , Disfunção Ventricular Esquerda/fisiopatologia
12.
Mol Biol Cell ; 27(3): 500-17, 2016 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-26631553

RESUMO

Nerve growth factor (NGF) promotes growth, differentiation, and survival of sensory neurons in the mammalian nervous system. Little is known about how NGF elicits faster axon outgrowth or how growth cones integrate and transform signal input to motor output. Using cultured mouse dorsal root ganglion neurons, we found that myosin II (MII) is required for NGF to stimulate faster axon outgrowth. From experiments inducing loss or gain of function of MII, specific MII isoforms, and vinculin-dependent adhesion-cytoskeletal coupling, we determined that NGF causes decreased vinculin-dependent actomyosin restraint of microtubule advance. Inhibition of MII blocked NGF stimulation, indicating the central role of restraint in directed outgrowth. The restraint consists of myosin IIB- and IIA-dependent processes: retrograde actin network flow and transverse actin bundling, respectively. The processes differentially contribute on laminin-1 and fibronectin due to selective actin tethering to adhesions. On laminin-1, NGF induced greater vinculin-dependent adhesion-cytoskeletal coupling, which slowed retrograde actin network flow (i.e., it regulated the molecular clutch). On fibronectin, NGF caused inactivation of myosin IIA, which negatively regulated actin bundling. On both substrates, the result was the same: NGF-induced weakening of MII-dependent restraint led to dynamic microtubules entering the actin-rich periphery more frequently, giving rise to faster elongation.


Assuntos
Actomiosina/metabolismo , Cones de Crescimento/fisiologia , Microtúbulos/metabolismo , Fator de Crescimento Neural/fisiologia , Animais , Crescimento Celular , Feminino , Fibronectinas/fisiologia , Gânglios Espinais/citologia , Laminina/fisiologia , Masculino , Camundongos Knockout , Miosina não Muscular Tipo IIA/metabolismo , Miosina não Muscular Tipo IIB/metabolismo , Fosforilação , Processamento de Proteína Pós-Traducional , Técnicas de Cultura de Tecidos , Proteínas rho de Ligação ao GTP/metabolismo
14.
Heart Lung Circ ; 24(6): 551-6, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25637940

RESUMO

BACKGROUND: Increasingly frail patients are being to be referred for invasive cardiac interventions and cardiac surgery. We aimed to evaluate the utility of a quick clinical assessment of frailty against a validated frailty assessment tool in an acute cardiology setting. METHODS: Forty-seven cardiology in-patients ≥70 years were recruited in this prospective study. All patients were first assessed by a senior cardiology registrar as either not-frail or frail. This was based on general observation and brief discussions. Following this, patients were administered the Reported Edmonton Frail Scale (REFS) questionnaire. After a registrar assessment, the foot-of-the bed frailty assessment was independently repeated by one or two consultant cardiologists. RESULTS: None of the three clinicians showed satisfactory similarity to the REFS score. When the two consultants were compared with the registrar, and with each other, the Cohen's kappa was only above 0.7 for the comparison between Consultant 1 and the registrar. Consultant 1 and the registrar were also significantly more likely to disagree at higher REFS score with a mean REFS score of 8.8. CONCLUSION: A quick foot-of-the-bed clinical assessment is not a reliable way to determine frailty.


Assuntos
Atividades Cotidianas , Procedimentos Cirúrgicos Cardíacos/métodos , Avaliação da Deficiência , Idoso Fragilizado , Avaliação Geriátrica/métodos , Idoso , Idoso de 80 Anos ou mais , Procedimentos Cirúrgicos Cardíacos/mortalidade , Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/epidemiologia , Estudos de Coortes , Feminino , Humanos , Masculino , Nova Zelândia , Estado Nutricional , Variações Dependentes do Observador , Estudos Prospectivos , Reprodutibilidade dos Testes , Medição de Risco , Índice de Gravidade de Doença , Estatísticas não Paramétricas , Inquéritos e Questionários , Resultado do Tratamento
15.
J Psychosom Res ; 77(2): 158-60, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25077859

RESUMO

OBJECTIVE: The development of somatoform illnesses is often associated with prior psychiatric illness and life stress. Broken heart syndrome has been associated with a range of stressors and we aimed to investigate if psychiatric illnesses are risk factors for developing broken heart syndrome. METHODS: We systematically assessed for antecedent psychiatric risk factors in two groups of cases (people who developed sporadic and earthquake-related broken heart syndrome) and compared them to a control group of healthy volunteers. RESULTS: We found that of the ten psychiatric risk factors examined, only 'neuroticism' significantly differed between participants with broken heart syndrome and healthy volunteers. CONCLUSION: There was no association between previous psychiatric illness and development of broken heart syndrome in this study. Clinical assessment of psychiatric risk factors may not identify patients at increased risk of broken heart syndrome.


Assuntos
Transtornos de Ansiedade , Transtornos Psicofisiológicos/diagnóstico , Transtornos Psicofisiológicos/psicologia , Cardiomiopatia de Takotsubo/diagnóstico , Cardiomiopatia de Takotsubo/psicologia , Adulto , Terremotos , Feminino , Humanos , Masculino , Transtornos Mentais/psicologia , Pessoa de Meia-Idade , Neuroticismo , Fatores de Risco
16.
N Z Med J ; 127(1396): 15-22, 2014 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-24997460

RESUMO

INTRODUCTION: A major earthquake struck Christchurch on 22 February 2011 causing extensive damage to the city and 185 direct fatalities. Within 4 days 21 postmenopausal women presented to Christchurch Hospital with stress cardiomyopathy. We were able to closely examine these patients in the immediate phase of presentation and at 12 months. METHODS: Patients were prospectively identified. Clinical details at presentation were recorded including basic characteristics, symptoms, investigations, results, treatments and complications. At 12 months, telephone interviews were conducted. Patients answered a structured questionnaire to assess their cardiac and general health concerns. Consenting patients also received three psychometric questionnaires to assess psychological wellbeing. RESULTS: The majority of patients had classic features of stress cardiomyopathy. Recovery was prompt with low complication rate. At 12 months, survival rate was 100%. Five patients had hospital readmissions early on--three of which were cardiac related. None had ongoing symptoms or stress cardiomyopathy recurrence. Seven patients had non-cardiac related medical problems. The psychometric questionnaires showed that none had a high level of health anxiety, general anxiety or depression. Four patients endorsed symptoms suggestive of borderline post-traumatic stress disorder. CONCLUSION: The Christchurch Earthquake stress cardiomyopathy cohort has had good short-term and medium-term outcomes without significant cardiac or psychological sequelae.


Assuntos
Terremotos , Cardiomiopatia de Takotsubo , Idoso , Idoso de 80 Anos ou mais , Angiografia Coronária , Progressão da Doença , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Nova Zelândia/epidemiologia , Cardiomiopatia de Takotsubo/diagnóstico , Cardiomiopatia de Takotsubo/epidemiologia
17.
Traffic ; 15(4): 418-32, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24443954

RESUMO

Variable requirements for actin during clathrin-mediated endocytosis (CME) may be related to regional or cellular differences in membrane tension. To compensate, local regulation of force generation may be needed to facilitate membrane curving and vesicle budding. Force generation is assumed to occur primarily through actin polymerization. Here we examine the role of myosin II using loss of function experiments. Our results indicate that myosin II acts on cortical actin scaffolds primarily in the plane of the plasma membrane (bottom arrow) to generate changes that are critical for enhancing CME progression.


Assuntos
Clatrina/fisiologia , Endocitose/fisiologia , Miosina Tipo II/fisiologia , Actinas/metabolismo , Animais , Camundongos , Camundongos Knockout , Músculos/fisiologia , Miosina Tipo II/genética , Transferrina/metabolismo
18.
ACS Nano ; 8(2): 1878-85, 2014 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-24444076

RESUMO

Electrospun nanofibers with uniaxial alignment have recently gained its popularity as scaffolds for neural tissue engineering. Many studies have demonstrated that the nanofibers could guide the neurites to extend along the direction of alignment, resembling the native hierarchy of the nerve tissue. However, the contact cues provided by the nanofibers can be far more complicated than just guiding the neurites to extend along them. In the current study, we used dorsal root ganglia as a model system to systematically investigate the interactions between neurites and uniaxially aligned nanofibers. We demonstrated, for the first time, that the neurites could not only project along the nanofibers, but also be directed to grow along a direction perpendicular to the aligned nanofibers, depending on the following parameters: (i) the density of nanofibers, (ii) the protein deposited on the surfaces of the nanofibers, and (iii) surface properties of the substrate on which the nanofibers were supported. We also investigated the pharmacological effect of myosin II inhibition on the nanofiber-guided growth of neurites by adding blebbistatin to the culture medium. Our findings offer new insights into the design of nanofiber-based scaffolds for nerve injury repair and will provide new guidelines for the construction of well-defined neuronal network architecture (the so-called neural circuits).


Assuntos
Neuritos , Microscopia Eletrônica de Varredura , Microscopia de Fluorescência , Engenharia Tecidual , Tecidos Suporte
19.
J Neurosci ; 33(41): 16131-45, 2013 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-24107946

RESUMO

Recent evidence suggests that endocytosis, not exocytosis, can be rate limiting for neurotransmitter release at excitatory CNS synapses during sustained activity and therefore may be a principal determinant of synaptic fatigue. At low stimulation frequencies, the probability of synaptic release is linked to the probability of synaptic retrieval such that evoked release results in proportional retrieval even for release of single synaptic vesicles. The exact mechanism by which the retrieval rates are coupled to release rates, known as compensatory endocytosis, remains unknown. Here we show that inactivation of presynaptic myosin II (MII) decreases the probability of synaptic retrieval. To be able to differentiate between the presynaptic and postsynaptic functions of MII, we developed a live cell substrate patterning technique to create defined neural circuits composed of small numbers of embryonic mouse hippocampal neurons and physically isolated from the surrounding culture. Acute application of blebbistatin to inactivate MII in circuits strongly inhibited evoked release but not spontaneous release. In circuits incorporating both control and MIIB knock-out cells, loss of presynaptic MIIB function correlated with a large decrease in the amplitude of evoked release. Using activity-dependent markers FM1-43 and horseradish peroxidase, we found that MII inactivation greatly slowed vesicular replenishment of the recycling pool but did not impede synaptic release. These results indicate that MII-driven tension or actin dynamics regulate the major pathway for synaptic vesicle retrieval. Changes in retrieval rates determine the size of the recycling pool. The resulting effect on release rates, in turn, brings about changes in synaptic strength.


Assuntos
Endocitose/fisiologia , Miosina Tipo II/metabolismo , Neurotransmissores/metabolismo , Sinapses/metabolismo , Transmissão Sináptica/fisiologia , Animais , Hipocampo/metabolismo , Camundongos , Camundongos Knockout , Microscopia Eletrônica de Transmissão , Neurônios/metabolismo , Técnicas de Patch-Clamp , Vesículas Sinápticas/metabolismo
20.
PLoS One ; 8(7): e68504, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23844213

RESUMO

BACKGROUND: Christchurch, New Zealand, was struck by 2 major earthquakes at 4:36 am on 4 September 2010, magnitude 7.1 and at 12:51 pm on 22 February 2011, magnitude 6.3. Both events caused widespread destruction. Christchurch Hospital was the region's only acute care hospital. It remained functional following both earthquakes. We were able to examine the effects of the 2 earthquakes on acute cardiac presentations. METHODS: Patients admitted under Cardiology in Christchurch Hospital 3 week prior to and 5 weeks following both earthquakes were analysed, with corresponding control periods in September 2009 and February 2010. Patients were categorised based on diagnosis: ST elevation myocardial infarction, Non ST elevation myocardial infarction, stress cardiomyopathy, unstable angina, stable angina, non cardiac chest pain, arrhythmia and others. RESULTS: There was a significant increase in overall admissions (p<0.003), ST elevation myocardial infarction (p<0.016), and non cardiac chest pain (p<0.022) in the first 2 weeks following the early morning September earthquake. This pattern was not seen after the early afternoon February earthquake. Instead, there was a very large number of stress cardiomyopathy admissions with 21 cases (95% CI 2.6-6.4) in 4 days. There had been 6 stress cardiomyopathy cases after the first earthquake (95% CI 0.44-2.62). Statistical analysis showed this to be a significant difference between the earthquakes (p<0.05). CONCLUSION: The early morning September earthquake triggered a large increase in ST elevation myocardial infarction and a few stress cardiomyopathy cases. The early afternoon February earthquake caused significantly more stress cardiomyopathy. Two major earthquakes occurring at different times of day differed in their effect on acute cardiac events.


Assuntos
Desastres , Terremotos , Infarto do Miocárdio/diagnóstico , Cardiomiopatia de Takotsubo/diagnóstico , Doença Aguda , Idoso , Angina Pectoris/diagnóstico , Angina Pectoris/fisiopatologia , Angina Instável/diagnóstico , Angina Instável/fisiopatologia , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/fisiopatologia , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/fisiopatologia , Dor no Peito/diagnóstico , Dor no Peito/fisiopatologia , Eletrocardiografia , Feminino , Hospitais Comunitários , Humanos , Masculino , Infarto do Miocárdio/fisiopatologia , Nova Zelândia , Admissão do Paciente/estatística & dados numéricos , Cardiomiopatia de Takotsubo/fisiopatologia , Fatores de Tempo
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