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1.
Intern Med J ; 54(6): 1010-1016, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38327096

RESUMO

BACKGROUND AND AIMS: Stroke is a leading cause of death in Aotearoa (New Zealand), and stroke reperfusion therapy is a key intervention. Sex differences in stroke care have previously been asserted internationally. This study assessed potential differences in stroke reperfusion rates and quality metrics by sex in Aotearoa (New Zealand). METHODS: This study used data from three overlapping sources. The National Stroke Reperfusion Register provided 4-year reperfusion data from 2018 to 2021 on all patients treated with reperfusion therapy (intravenous thrombolysis and thrombectomy), including time delays, treatment rates, mortality and complications. Linkage to Ministry of Health administrative and REGIONS Care study data provided an opportunity to control for confounders and explore potential mechanisms. T-test and Wilcoxon rank-sum analyses were used for continuous variables, while the chi-squared test and logistic regression were used for comparing dichotomous variables. RESULTS: Fewer women presented with ischaemic stroke (12 186 vs 13 120) and were 4.2 years older than men (median (interquartile range (IQR)) 79 (68-86) vs 73 (63-82) years). Women were overall less likely to receive reperfusion therapy (13.9% (1704) vs 15.8% (2084), P < 0.001) with an adjusted odds ratio of 0.83 (0.77-0.90), P < 0.001. The adjusted odds ratio for thrombolysis was lower for women (0.82 (0.76-0.89), P < 0.001), but lower rates of thrombectomy fell just short of statistical significance ((0.89 (0.79-1.00), P = 0.05). There were no significant differences in complications, delays or documented reasons for non-thrombolysis. CONCLUSIONS: Women were less likely to receive thrombolysis, even after adjusting for age and stroke severity. We found no definitive explanation for this disparity.


Assuntos
Trombectomia , Terapia Trombolítica , Humanos , Nova Zelândia/epidemiologia , Feminino , Masculino , Idoso , Idoso de 80 Anos ou mais , Pessoa de Meia-Idade , Terapia Trombolítica/estatística & dados numéricos , Fatores Sexuais , Trombectomia/estatística & dados numéricos , Reperfusão/estatística & dados numéricos , Acidente Vascular Cerebral/terapia , Acidente Vascular Cerebral/epidemiologia , AVC Isquêmico/terapia , AVC Isquêmico/epidemiologia , Tempo para o Tratamento/estatística & dados numéricos , Sistema de Registros
2.
Pract Neurol ; 23(6): 501-503, 2023 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-37524438

RESUMO

Classic Raymond syndrome is a rare neurological presentation comprising ipsilateral abducens palsy, contralateral facial paresis and contralateral hemiparesis. We present a man in his late 60s who presented with diplopia, dysarthria and right-sided limb weakness. This syndrome is one of a group of 'crossed paralyses' of the caudal pons.


Assuntos
Isquemia Encefálica , Paralisia Facial , AVC Isquêmico , Acidente Vascular Cerebral , Masculino , Humanos , Isquemia Encefálica/complicações , Isquemia Encefálica/diagnóstico por imagem , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/diagnóstico por imagem , Ponte/diagnóstico por imagem , Paralisia Facial/diagnóstico , Paralisia Facial/etiologia , Paresia/etiologia
3.
Adv Health Sci Educ Theory Pract ; 27(1): 147-165, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34687383

RESUMO

Open-book examinations (OBEs) will likely become increasingly important assessment tools. We investigated how access to open-book resources affected questions testing factual recall, which might be easy to look-up, versus questions testing higher-order cognitive domains. Few studies have investigated OBEs using modern Internet resources or as summative assessments. We compared performance on an examination conducted as a traditional closed-book exam (CBE) in 2019 (N = 320) and a remote OBE with free access to Internet resources in 2020 (N = 337) due to COVID-19. This summative, end-of-year assessment focused on basic science for second-year medical students. We categorized questions by Bloom's taxonomy ('Remember', versus 'Understand/Apply'). We predicted higher performance on the OBE, driven by higher performance on 'Remember' questions. We used an item-centric analysis by using performance per item over all examinees as the outcome variable in logistic regression, with terms 'Open-Book, 'Bloom Category' and their interaction. Performance was higher on OBE questions than CBE questions (OR 2.2, 95% CI: 2.14-2.39), and higher on 'Remember' than 'Understand/Apply' questions (OR 1.13, 95% CI: 1.09-1.19). The difference in performance between 'Remember' and 'Understand/Apply' questions was greater in the OBE than the CBE ('Open-Book' * 'Bloom Category' interaction: OR 1.2, 95% CI: 1.19-1.37). Access to open-book resources had a greater effect on performance on factual recall questions than higher-order questions, though performance was higher in the OBE overall. OBE design must consider how searching for information affects performance, particularly on questions measuring different domains of knowledge.


Assuntos
COVID-19 , Estudantes de Medicina , COVID-19/diagnóstico , COVID-19/epidemiologia , Cognição , Avaliação Educacional , Humanos , Faculdades de Medicina
4.
Eur J Neurol ; 29(3): 761-770, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34811840

RESUMO

BACKGROUND AND PURPOSE: To explore the prevalence, risk factors, time correlation, characteristics and clinical outcome of dural arteriovenous fistulas (dAVFs) in a cerebral venous thrombosis (CVT) population. METHODS: We included patients from the International CVT Consortium registries. Diagnosis of dAVF was confirmed centrally. We assessed the prevalence and risk factors for dAVF among consecutive CVT patients and investigated its impact on clinical outcome using logistic regression analysis. We defined poor outcome as modified Rankin Scale score 3-6 at last follow-up. RESULTS: dAVF was confirmed in 29/1218 (2.4%) consecutive CVT patients. The median (interquartile range [IQR]) follow-up time was 8 (5-23) months. Patients with dAVF were older (median [IQR] 53 [44-61] vs. 41 [29-53] years; p < 0.001), more frequently male (69% vs. 33%; p < 0.001), more often had chronic clinical CVT onset (>30 days: 39% vs. 7%; p < 0.001) and sigmoid sinus thrombosis (86% vs. 51%; p < 0.001), and less frequently had parenchymal lesions (31% vs. 55%; p = 0.013) at baseline imaging. Clinical outcome at last follow-up did not differ between patients with and without dAVF. Additionally, five patients were confirmed with dAVF from non-consecutive CVT cohorts. Among all patients with CVT and dAVF, 17/34 (50%) had multiple fistulas and 23/34 (68%) had cortical venous drainage. Of 34 patients with dAVF with 36 separate CVT events, 3/36 fistulas (8%) were diagnosed prior to, 20/36 (56%) simultaneously and 13/36 after (36%, median 115 [IQR 38-337] days) diagnosis of CVT. CONCLUSIONS: Dural arteriovenous fistulas occur in at least 2% of CVT patients and are associated with chronic CVT onset, older age and male sex. Most CVT-related dAVFs are detected simultaneously or subsequently to diagnosis of CVT.


Assuntos
Malformações Vasculares do Sistema Nervoso Central , Trombose Intracraniana , Trombose dos Seios Intracranianos , Trombose Venosa , Malformações Vasculares do Sistema Nervoso Central/complicações , Malformações Vasculares do Sistema Nervoso Central/diagnóstico por imagem , Malformações Vasculares do Sistema Nervoso Central/epidemiologia , Humanos , Trombose Intracraniana/complicações , Trombose Intracraniana/diagnóstico por imagem , Trombose Intracraniana/epidemiologia , Masculino , Fatores de Risco , Trombose dos Seios Intracranianos/complicações , Trombose dos Seios Intracranianos/epidemiologia , Trombose Venosa/complicações , Trombose Venosa/epidemiologia
5.
Neurology ; 95(12): e1706-e1715, 2020 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-32759191

RESUMO

OBJECTIVE: To identify characteristics, predictors, and outcomes of acute symptomatic seizures (ASS) in cerebral venous thrombosis (CVT), we investigated 1,281 consecutive adult patients with CVT included from 12 hospitals within the International CVT Consortium. METHODS: We defined ASS as any seizure between symptom onset and 7 days after diagnosis of CVT. We stratified ASS into prediagnosis and solely postdiagnosis ASS. Status epilepticus (SE) was also analyzed separately. We analyzed predictors for ASS and the association between ASS and clinical outcome (modified Rankin Scale) with multivariable logistic regression. RESULTS: Of 1,281 eligible patients, 441 (34%) had ASS. Baseline predictors for ASS were intracerebral hemorrhage (ICH; adjusted odds ratio [aOR] 4.1, 95% confidence interval [CI] 3.0-5.5), cerebral edema/infarction without ICH (aOR 2.8, 95% CI 2.0-4.0), cortical vein thrombosis (aOR 2.1, 95% CI 1.5-2.9), superior sagittal sinus thrombosis (aOR 2.0, 95% CI 1.5-2.6), focal neurologic deficit (aOR 1.9, 95% CI 1.4-2.6), sulcal subarachnoid hemorrhage (aOR 1.6, 95% CI 1.1-2.5), and female-specific risk factors (aOR 1.5, 95% CI 1.1-2.1). Ninety-three (7%) patients had solely postdiagnosis ASS, best predicted by cortical vein thrombosis (positive/negative predictive value 22%/92%). Eighty (6%) patients had SE, independently predicted by ICH, focal neurologic deficits, and cerebral edema/infarction. Neither ASS nor SE was independently associated with outcome. CONCLUSION: ASS occurred in one-third of patients with CVT and was associated with brain parenchymal lesions and thrombosis of the superficial system. In the absence of prediagnosis ASS, no subgroup was identified with sufficient risk of postdiagnosis ASS to justify prophylactic antiepileptic drug treatment. We found no association between ASS and outcome.


Assuntos
Trombose Intracraniana/complicações , Convulsões/etiologia , Trombose Venosa/complicações , Adulto , Veias Cerebrais/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco
6.
Neurology ; 95(12): e1716-e1723, 2020 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-32759195

RESUMO

OBJECTIVE: To examine the incidence, characteristics, treatment, and predictors of late seizures (LS) after cerebral venous thrombosis (CVT), we described these features in a registry of 1,127 patients with CVT. METHODS: We included consecutive adult patients from an international consortium of 12 hospital-based CVT registries. We excluded patients with a history of epilepsy or with <8 days of follow-up. We defined LS as seizures occurring >7 days after diagnosis of CVT. We used multivariable Cox regression to identify predictors of LS. RESULTS: We included 1,127 patients with CVT. During a median follow-up of 2.0 years (interquartile range [IQR] 1.0-6.3), 123 patients (11%) experienced ≥1 LS (incidence rate for first LS 30 per 1,000 person-years, 95% confidence interval [CI] 25-35). Median time to first LS was 5 months (IQR 1-16 months). Baseline predictors of LS included status epilepticus in the acute phase (hazard ratio [HR] 7.0, 95% CI 3.9-12.6), decompressive hemicraniectomy (HR 4.2, 95% CI 2.4-7.3), acute seizure(s) without status epilepticus (HR 4.1, 95% CI 2.5-6.5), subdural hematoma (HR 2.3, 95% CI 1.1-4.9), and intracerebral hemorrhage (HR 1.9, 95% CI 1.1-3.1). Eighty-five patients (70% of patients with LS) experienced a recurrent seizure during follow-up, despite the fact that 94% received antiepileptic drug treatment after the first LS. CONCLUSION: During a median follow-up of 2 years, ≈1 in 10 patients with CVT had LS. Patients with baseline intracranial bleeding, patients with acute symptomatic seizures, and those who underwent decompressive hemicraniectomy were at increased risk of developing LS. The high recurrence risk of LS justifies epilepsy diagnosis after a first LS.


Assuntos
Trombose Intracraniana/complicações , Convulsões/epidemiologia , Convulsões/etiologia , Trombose Venosa/complicações , Adulto , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Recidiva , Fatores de Risco
7.
J Clin Endocrinol Metab ; 100(4): 1520-8, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25664601

RESUMO

CONTEXT: Prognosis in patients with neuroendocrine tumors (NETs) is often poor, frequently reflecting delayed diagnosis. Hence, accurate and practical NET markers are needed. Cocaine- and amphetamine-regulated transcript (CART) peptide is a potential novel NET marker. DESIGN AND PARTICIPANTS: Circulating levels of CART peptide and the established NET markers chromogranin A (CgA) and chromogranin B (CgB) were measured using RIA in 353 patients with NET (normal renal function) and in controls. Clinical data were collected retrospectively. MAIN OUTCOME MEASURE(S): The comparative and combined utility of CART, CgA, and CgB for diagnosis and assessment of disease progression was measured in different NET subtypes. RESULTS: CgA and CgB in combination improved diagnostic accuracy in patients with gut NETs, nongastroenteropancreatic NETs, and NETs with an unknown primary origin compared with each biomarker alone. Measuring CART did not further improve diagnosis in these NET subtypes. For pancreatic NETs, CgB was superior to CgA and CART in detecting stable disease (P < .007), whereas CgA and CART in combination were most effective in identifying progressive disease. In phaeochromocytomas/paragangliomas (PCC/PGL), CART was the most useful biomarker for identifying stable (P < .001) and progressive (P = .001) disease. Consistent with this, plasma CART decreased following PCC/PGL tumor resection, remaining low in all patients in remission, but increasing in those with progressive disease. CONCLUSIONS: CART is a useful marker for identifying progressive pancreatic NETs. CART is superior to CgA and CgB in detecting stable and progressive PCC/PGLs, and may have a role as a surveillance marker for PCC/PGL patients.


Assuntos
Neoplasias das Glândulas Suprarrenais/diagnóstico , Biomarcadores Tumorais/sangue , Cromogranina A/sangue , Cromogranina B/sangue , Proteínas do Tecido Nervoso/sangue , Tumores Neuroendócrinos/diagnóstico , Paraganglioma/diagnóstico , Feocromocitoma/diagnóstico , Neoplasias das Glândulas Suprarrenais/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Técnicas de Diagnóstico Endócrino , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tumores Neuroendócrinos/sangue , Paraganglioma/sangue , Feocromocitoma/sangue , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Adulto Jovem
8.
Int J Obes (Lond) ; 39(3): 447-55, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25219528

RESUMO

BACKGROUND: High-protein diets promote weight loss and subsequent weight maintenance, but are difficult to adhere to. The mechanisms by which protein exerts these effects remain unclear. However, the amino acids produced by protein digestion may have a role in driving protein-induced satiety. METHODS: We tested the effects of a range of amino acids on food intake in rodents and identified l-cysteine as the most anorexigenic. Using rodents we further studied the effect of l-cysteine on food intake, behaviour and energy expenditure. We proceeded to investigate its effect on neuronal activation in the hypothalamus and brainstem before investigating its effect on gastric emptying and gut hormone release. The effect of l-cysteine on appetite scores and gut hormone release was then investigated in humans. RESULTS: l-Cysteine dose-dependently decreased food intake in both rats and mice following oral gavage and intraperitoneal administration. This effect did not appear to be secondary to behavioural or aversive side effects. l-Cysteine increased neuronal activation in the area postrema and delayed gastric emptying. It suppressed plasma acyl ghrelin levels and did not reduce food intake in transgenic ghrelin-overexpressing mice. Repeated l-cysteine administration decreased food intake in rats and obese mice. l-Cysteine reduced hunger and plasma acyl ghrelin levels in humans. CONCLUSIONS: Further work is required to determine the chronic effect of l-cysteine in rodents and humans on appetite and body weight, and whether l-cysteine contributes towards protein-induced satiety.


Assuntos
Depressores do Apetite/farmacologia , Apetite/efeitos dos fármacos , Cisteína/farmacologia , Ingestão de Alimentos/efeitos dos fármacos , Grelina/antagonistas & inibidores , Adulto , Animais , Depressores do Apetite/administração & dosagem , Cisteína/administração & dosagem , Relação Dose-Resposta a Droga , Feminino , Hormônios Gastrointestinais/metabolismo , Grelina/metabolismo , Humanos , Hipotálamo/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , RNA Mensageiro , Ratos , Ratos Wistar , Receptores dos Hormônios Gastrointestinais/metabolismo , Receptores de Neuropeptídeos/metabolismo , Saciação
9.
J Chem Phys ; 141(3): 034706, 2014 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-25053333

RESUMO

Density functional theory calculations are often used to interpret experimental shifts in core level binding energies. Calculations based on gradient-corrected (GC) exchange-correlation functionals are known to reproduce measured core level shifts (CLS) of isolated molecules and metal surfaces with reasonable accuracy. In the present study, we discuss a series of examples where the shifts calculated within a GC-functional significantly deviate from the experimental values, namely the CLS of C 1s in ethyl trifluoroacetate, Pd 3d in PdO and the O 1s shift for CO adsorbed on PdO(101). The deviations are traced to effects of the electronic self-interaction error with GC-functionals and substantially better agreements between calculated and measured CLS are obtained when a fraction of exact exchange is used in the exchange-correlation functional.

10.
J Phys Condens Matter ; 26(5): 055003, 2014 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-24334623

RESUMO

We have studied the oxidation of CO over Rh(100) using high pressure x-ray photoelectron spectroscopy under CO and O2 pressures ranging from 0.01 to 1 mbar. The results show a very low or no conversion for the CO covered surface found at low temperatures, while the activity rises slightly when the temperature is high enough for some CO to desorb, exposing surface sites for dissociative O2 adsorption. As the temperature is increased further, more CO desorbs and oxygen replaces CO as the dominating species at the surface. At the same time we find a sudden increase in the reactivity, such that all CO that reaches the surface is instantly transformed into CO2. We find that the O coverage in the active state is highly dependent on the total pressure and, although we do not detect any presence of a surface oxide as in previous surface x-ray diffraction studies, the highest O coverage indicates that the surface is close to being oxidized.

11.
Ann Clin Biochem ; 51(Pt 1): 8-21, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23939195

RESUMO

Neuroendocrine neoplasia (NEN) is a heterogeneous group of tumours and often represents a therapeutic challenge to clinicians. The peptides chromogranin A (CgA), chromogranin B (CgB) and cocaine- and amphetamine-regulated transcript (CART) are widely distributed throughout the neuroendocrine system. CgA and CgB have been used as general NEN biomarkers for many years, while CART has only recently been identified. Of these biomarkers, CgA is the most commonly used. However, circulating CgA concentrations exhibit considerable intra-individual biological variation, are altered by proton pump inhibitors (PPIs) and somatostatin analogues and are elevated in non-NEN malignancies. Therefore, interpretation of CgA results must be in the context of these confounding factors. The effects of treatment and non-NEN conditions on circulating CgB and CART concentrations are less well understood. CgB is less affected by impaired renal function and PPIs than CgA; while, circulating CART concentrations lack a diurnal variation in humans and are more reliable markers of pancreatic NEN malignancy than CgA. The utility of circulating CgA measurements in NEN prognosis, surveillance and disease recurrence has been widely investigated. However, the utility of CgB and CART in NEN management is yet to be elucidated. Further studies are needed to establish whether CgB and CART are useful alternatives to CgA.


Assuntos
Cromogranina A/genética , Cromogranina B/genética , Proteínas do Tecido Nervoso/genética , Tumores Neuroendócrinos/genética , Biomarcadores Tumorais/genética , Humanos , Tumores Neuroendócrinos/diagnóstico , Tumores Neuroendócrinos/patologia , Pâncreas/metabolismo , Pâncreas/patologia , Prognóstico , Somatostatina/metabolismo
12.
Diabet Med ; 30(12): 1495-9, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23796160

RESUMO

AIM: Increased body iron is associated with insulin resistance. Hepcidin is the key hormone that negatively regulates iron homeostasis. We hypothesized that individuals with insulin resistance have inadequate hepcidin levels for their iron load. METHODS: Serum concentrations of the active form of hepcidin (hepcidin-25) and hepcidin:ferritin ratio were evaluated in participants with Type 2 diabetes (n = 33, control subjects matched for age, gender and BMI, n = 33) and participants with polycystic ovary syndrome (n = 27, control subjects matched for age and BMI, n = 16). To investigate whether any changes observed were associated with insulin resistance rather than insulin deficiency or hyperglycaemia per se, the same measurements were made in participants with Type 1 diabetes (n = 28, control subjects matched for age, gender and BMI, n = 30). Finally, the relationship between homeostasis model assessment of insulin resistance and serum hepcidin:ferritin ratio was explored in overweight or obese participants without diabetes (n = 16). RESULTS: Participants with Type 2 diabetes had significantly lower hepcidin and hepcidin:ferritin ratio than control subjects (P < 0.05 and P < 0.01, respectively). Participants with polycystic ovary syndrome had a significantly lower hepcidin:ferritin ratio than control subjects (P < 0.05). There was no significant difference in hepcidin or hepcidin:ferritin ratio between participants with Type 1 diabetes and control subjects (P = 0.88 and P = 0.94). Serum hepcidin:ferritin ratio inversely correlated with homeostasis model assessment of insulin resistance (r = -0.59, P < 0.05). CONCLUSION: Insulin resistance, but not insulin deficiency or hyperglycaemia per se, is associated with inadequate hepcidin levels. Reduced hepcidin concentrations may cause increased body iron stores in insulin-resistant states.


Assuntos
Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 2/sangue , Ferritinas/sangue , Hepcidinas/sangue , Resistência à Insulina , Síndrome do Ovário Policístico/sangue , Adulto , Glicemia/metabolismo , Feminino , Ferritinas/deficiência , Hepcidinas/deficiência , Homeostase , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Masculino , Pessoa de Meia-Idade
13.
Int J Obes (Lond) ; 37(10): 1391-8, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23337772

RESUMO

BACKGROUND: Glucagon and glucagon-like peptide-1 (GLP-1) are evolutionarily related anorectic hormones. Glucagon also increases energy expenditure. The combination of glucagon and GLP-1 could cause weight loss through a simultaneous reduction in food intake and increased energy expenditure. However, the effect of combined administration of glucagon and GLP-1 on food intake and neuronal activation has not previously been studied. Furthermore, the effect of glucagon on neuronal activation in appetite regulating centres has not been assessed. Characterisation of the effects of glucagon when administered singly and in combination with GLP-1 on neuronal activation will be important for determining the mechanism of action of related potential antiobesity therapies. OBJECTIVES: To investigate the effects of peripherally administered GLP-1 and glucagon on food intake, neuronal activation and blood glucose in mice when administered individually and in combination. METHODOLOGY: Food intake, blood glucose and c-fos expression in the hypothalamus, amygdala and brainstem were measured in response to GLP-1 and glucagon, alone and in combination. RESULTS: Peripherally administered GLP-1 and glucagon decreased food intake and increased c-fos expression in the brainstem and amygdala. Doses of GLP-1 and glucagon that individually did not significantly affect feeding, in combination were anorectic and stimulated neuronal activation in the area postrema (AP) and central nucleus of the amygdala. Combined administration of GLP-1 and glucagon prevented the acute hyperglycemic effect of glucagon alone. CONCLUSION: Anorectic doses of glucagon and GLP-1 induced similar patterns of c-fos expression. Combined administration of low dose GLP-1 and glucagon inhibited food intake and induced c-fos expression in the AP and amygdala. The combination of both hormones may offer the opportunity to utilise the beneficial effects of reduced food intake and increased energy expenditure, and may therefore be a potential treatment for obesity.


Assuntos
Tonsila do Cerebelo/metabolismo , Apetite/fisiologia , Tronco Encefálico/metabolismo , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Glucagon/metabolismo , Proteínas Proto-Oncogênicas c-fos/metabolismo , Animais , Apetite/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ingestão de Alimentos/efeitos dos fármacos , Metabolismo Energético , Glucagon/farmacologia , Peptídeo 1 Semelhante ao Glucagon/farmacologia , Injeções Intraperitoneais , Masculino , Camundongos , Proteínas Proto-Oncogênicas c-fos/efeitos dos fármacos
14.
Phys Rev Lett ; 110(11): 117601, 2013 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-25166577

RESUMO

We present high-pressure x-ray photoelectron spectroscopy (HP-XPS) and first-principles kinetic Monte Carlo study addressing the nature of the active surface in CO oxidation over Pd(100). Simultaneously measuring the chemical composition at the surface and in the near-surface gas phase, we reveal both O-covered pristine Pd(100) and a surface oxide as stable, highly active phases in the near-ambient regime accessible to HP-XPS. Surprisingly, no adsorbed CO can be detected during high CO(2) production rates, which can be explained by a combination of a remarkably short residence time of the CO molecule on the surface and mass-transfer limitations in the present setup.

15.
Eur J Nucl Med Mol Imaging ; 39(8): 1266-70, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22526961

RESUMO

PURPOSE: To compare the sensitivity of (123)I-metaiodobenzylguanidine (MIBG) SPECT and (68)Ga-DOTATATE PET/CT in detecting phaeochromocytomas (PCC) and paragangliomas (PGL) in the initial diagnosis and follow-up of patients with PCC and PGL disease. METHODS: Retrospective analysis of 15 patients with PCC/PGL who had contemporaneous (123)I-MIBG and (68)Ga-DOTATATE imaging. RESULTS: Of the 15 patients in the series, 8 were concordant with both modalities picking up clinically significant lesions. There were no patients in whom both modalities failed to pick up clinically significant lesions. There was discordance in seven patients: 5 had positive (68)Ga-DOTATATE and negative (123)I-MIBG, and 2 (12 and 14) had negative (68)Ga-DOTATATE and positive (123)I-MIBG. Utilizing (123)I-MIBG as the gold standard, (68)Ga-DOTATATE had a sensitivity of 80 % and a positive predictive value of 62 %. The greatest discordance was in head and neck lesions, with the lesions in 4 patients being picked up by (68)Ga-DOTATATE and missed by (123)I-MIBG. On a per-lesion analysis, cross-sectional (CT and MRI) and (68)Ga-DOTATATE was superior to (123)I-MIBG in detecting lesions in all anatomical locations, and particularly bony lesions. CONCLUSION: First, (68)Ga-DOTATATE should be considered as a first-line investigation in patients at high risk of PGL and metastatic disease, such as in the screening of carriers for mutations associated with familial PGL syndromes. Second, if (123)I-MIBG does not detect lesions in patients with a high pretest probability of PCC or PGL, (68)Ga-DOTATATE should be considered as the next investigation. Third, (68)Ga-DOTATATE hould be considered in preference to (123)I-MIBG in patients in whom metastatic spread, particularly to the bone, is suspected.


Assuntos
3-Iodobenzilguanidina , Neoplasias das Glândulas Suprarrenais/diagnóstico por imagem , Imagem Multimodal/métodos , Compostos Organometálicos , Paraganglioma/diagnóstico por imagem , Feocromocitoma/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Tomografia Computadorizada por Raios X , Adolescente , Adulto , Seguimentos , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Sensibilidade e Especificidade , Adulto Jovem
16.
J Clin Endocrinol Metab ; 97(4): 1187-93, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22278424

RESUMO

CONTEXT: With adequate dose titration, pegvisomant normalizes IGF-I in up to 97% of patients with acromegaly. Pegvisomant is indicated for treatment-resistant disease but is expensive, particularly at a high dose. It has been used successfully in combination with somatostatin analogs. However, there are no therapeutic reports of pegvisomant in combination with dopamine agonists. Cabergoline is orally active, well-tolerated, and relatively inexpensive, and as monotherapy for acromegaly it is reported to normalize IGF-I in up to 30% of patients. OBJECTIVE: The aim of the study was to investigate the efficacy of cabergoline monotherapy and pegvisomant in combination with cabergoline to control serum IGF-I in patients with active acromegaly. Twenty-four patients were recruited into a United Kingdom, multicenter, open-label, prospective clinical trial. MAIN OUTCOME MEASURE: We measured the change in serum IGF-I. RESULTS: After 18 wk of dose titration to a maximum dose of 0.5 mg once daily, cabergoline monotherapy did not significantly reduce IGF-I (454 ± 219 baseline vs. 389 ± 192 ng/ml cabergoline), although two patients did normalize IGF-I. The addition of 10 mg pegvisomant daily for 12 wk significantly reduced IGF-I (389 ± 192 ng/ml cabergoline vs. 229 ± 101 ng/ml combination), and 68% achieved a normal IGF-I. Twelve weeks after cabergoline withdrawal, while continuing to receive pegvisomant 10 mg, only 26% of patients maintained an IGF-I within the reference range (229 ± 101 ng/ml combination vs. 305 ± 177 ng/ml pegvisomant). There were no significant changes in liver transaminases or glucose metabolism throughout the study. CONCLUSION: These data suggest that combination treatment with cabergoline and pegvisomant is more effective at reducing IGF-I levels than either cabergoline or pegvisomant monotherapy.


Assuntos
Acromegalia/tratamento farmacológico , Agonistas de Dopamina/uso terapêutico , Ergolinas/uso terapêutico , Hormônio do Crescimento Humano/análogos & derivados , Receptores da Somatotropina/antagonistas & inibidores , Acromegalia/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Cabergolina , Agonistas de Dopamina/administração & dosagem , Agonistas de Dopamina/efeitos adversos , Monitoramento de Medicamentos , Resistência a Medicamentos/efeitos dos fármacos , Quimioterapia Combinada/efeitos adversos , Ergolinas/administração & dosagem , Ergolinas/efeitos adversos , Feminino , Hormônio do Crescimento Humano/administração & dosagem , Hormônio do Crescimento Humano/efeitos adversos , Hormônio do Crescimento Humano/sangue , Hormônio do Crescimento Humano/uso terapêutico , Humanos , Fator de Crescimento Insulin-Like I/análise , Masculino , Pessoa de Meia-Idade , Pacientes Desistentes do Tratamento , Reino Unido
17.
J Phys Chem Lett ; 3(6): 678-82, 2012 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-26286272

RESUMO

The active phase of Pd during methane oxidation is a long-standing puzzle, which, if solved, could provide routes for design of improved catalysts. Here, density functional theory and in situ surface X-ray diffraction are used to identify and characterize atomic sites yielding high methane conversion. Calculations are performed for methane dissociation over a range of Pd and PdOx surfaces and reveal facile dissociation on either under-coordinated Pd sites in PdO(101) or metallic surfaces. The experiments show unambiguously that high methane conversion requires sufficiently thick PdO(101) films or metallic Pd, in full agreement with the calculations. The established link between high activity and atomic structure enables rational design of improved catalysts.

18.
Eur J Clin Nutr ; 65(4): 508-13, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21245879

RESUMO

BACKGROUND/OBJECTIVE: The sweet-taste receptor (T1r2+T1r3) is expressed by enteroendocrine L-cells throughout the gastrointestinal tract. Application of sucralose (a non-calorific, non-metabolisable sweetener) to L-cells in vitro stimulates glucagon-like peptide (GLP)-1 secretion, an effect that is inhibited with co-administration of a T1r2+T1r3 inhibitor. We conducted a randomised, single-blinded, crossover study in eight healthy subjects to investigate whether oral ingestion of sucralose could stimulate L-cell-derived GLP-1 and peptide YY (PYY) release in vivo. METHODS: Fasted subjects were studied on 4 study days in random order. Subjects consumed 50 ml of either water, sucralose (0.083% w/v), a non-sweet, glucose-polymer matched for sweetness with sucralose addition (50% w/v maltodextrin+0.083% sucralose) or a modified sham-feeding protocol (MSF=oral stimulation) of sucralose (0.083% w/v). Appetite ratings and plasma GLP-1, PYY, insulin and glucose were measured at regular time points for 120 min. At 120 min, energy intake at a buffet meal was measured. RESULTS: Sucralose ingestion did not increase plasma GLP-1 or PYY. MSF of sucralose did not elicit a cephalic phase response for insulin or GLP-1. Maltodextrin ingestion significantly increased insulin and glucose compared with water (P<0.001). Appetite ratings and energy intake were similar for all groups. CONCLUSIONS: At this dose, oral ingestion of sucralose does not increase plasma GLP-1 or PYY concentrations and hence, does not reduce appetite in healthy subjects. Oral stimulation with sucralose had no effect on GLP-1, insulin or appetite.


Assuntos
Apetite/efeitos dos fármacos , Hormônios Gastrointestinais/metabolismo , Sacarose/análogos & derivados , Edulcorantes/farmacologia , Adulto , Glicemia/análise , Estudos Cross-Over , Ingestão de Energia , Feminino , Peptídeo 1 Semelhante ao Glucagon/sangue , Humanos , Insulina/sangue , Masculino , Peptídeo YY/sangue , Método Simples-Cego , Sacarose/farmacologia , Adulto Jovem
19.
SEMERGEN, Soc. Esp. Med. Rural Gen. (Ed. impr.) ; 35(6): 270-272, jun.-jul. 2009. graf
Artigo em Espanhol | IBECS | ID: ibc-140857

RESUMO

Objetivos. Estudiar la cumplimentación del ayuno correcto previo a la realización del análisis de sangre y averiguar si los profesionales sanitarios aconsejan el ayuno de 12 horas. Sujetos y métodos: Se pasó una encuesta a todos los adultos que se realizaron una analítica de sangre en un centro de salud rural (CSR) y en un laboratorio hospitalario (LH) durante periodos de dos y una semanas respectivamente. Se recogieron los datos de: sexo, edad, si comieron después de las 20 horas del día previo, si sabían que debían guardar ayuno y si algún profesional sanitario les advirtió de mantener un ayuno de 12 horas. Resultados: En el CSR se recogieron 202 encuestas, el 58,1% eran mujeres y la edad media de 53,7 ± 18,7. Conocían la importancia del ayuno el 95,3% y comieron después de las 20 horas del día previo el 66,5%. Al 86,6% nadie les dijo que debían guardar ayuno de 12 horas. En el LH se recogieron 243 encuestas, el 54% eran hombres y la edad media, de 54,1 ± 18,7. Conocían la importancia del ayuno el 96,5% y comieron después de las 20 horas el 78,2%. Al 90,2% nadie les dijo que debían guardar ayuno de 12 horas. Conclusiones: La mayoría de la población conoce la importancia del ayuno. El porcentaje de observancia del ayuno de 12 horas es muy bajo, aunque algo mayor en la población rural. Los sanitarios no informamos adecuadamente a nuestros pacientes (AU)


Objetives: 1. Study correct fasting compliance prior to the performance of the blood analysis. 2. Discover if the health care professionals have recommended 12-hour fasting. Subjects and methods: All the adults who underwent a blood test in a rural health care center (RHCS) and in a hospital laboratory (HL) during a two week and one week period, respectively, were surveyed. The survey collected: gender, age, if the subject had eaten after 8 p.m. on the day before the test, if they had known they had to fast and if any health care professional had told them to maintain a 12-hour fast. Results: In the RHCS, 202 surveys were collected (58.1% women). Mean age was 53.7 ± 18.7. A total of 95.3% had known the importance of fasting, and 66.5% had eaten after 8 p.m. the day before the test. A total of 86.6% had not been informed they had to fast for 12 hours. In the HL, 243 surveys were collected, 54% men. Mean age 54.1 ± 18.7. A total of 96.5% knew about the importance of fasting, and 78.2 had eaten after 8 p.m. the day before. A total of 90.2% had not been informed of the need to follow a 12- fasting period. Conclusions: Most of the population knows the importance of fasting. However, observance of a 12-hour fasting period is low, somewhat greater in the rural population. The health care professionals do not adequately inform their patients (AU)


Assuntos
Feminino , Humanos , Masculino , Serviços de Laboratório Clínico/ética , Serviços de Laboratório Clínico , Técnicas de Laboratório Clínico/instrumentação , Coleta de Amostras Sanguíneas/enfermagem , Participação do Paciente/psicologia , Pesquisas sobre Atenção à Saúde/instrumentação , Serviços de Laboratório Clínico/legislação & jurisprudência , Serviços de Laboratório Clínico , Técnicas de Laboratório Clínico/métodos , Coleta de Amostras Sanguíneas/métodos , Participação do Paciente , Pesquisas sobre Atenção à Saúde/métodos
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