66 research outputs found

    Secretin facilitates GABA transmission in the cerebellum

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    Secretin was the first hormone discovered in human history, and yet, its function as a neuropeptide has been overlooked in the past. The recent discovery of the potential use of secretin in treating autistic patients, together with the conflicting reports on its effectiveness, urges an in-depth investigation of this issue. We show here that in the rat cerebellar cortex, mRNAs encoding secretin are localized in the Purkinje cells, whereas those of its receptor are found in both Purkinje cells and GABAergic interneurons. Immunoreactivity for secretin is localized in the soma and dendrites of Purkinje cells. In addition, secretin facilitates evoked, spontaneous, and miniature IPSCs recorded from Purkinje cells. We propose that secretin is released from the somatodendritic region of Purkinje cells and serves as a retrograde messenger modulating GABAergic afferent activity.published_or_final_versio

    瑪麗醫院進行腹腔鏡腎臟切除術的早期經驗

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    OBJECTIVE: To report our early experience of laparoscopic nephrectomy. DESIGN: Prospective data collection. SETTING: Queen Mary Hospital, Hong Kong. PATIENTS: Transperitoneal laparoscopic nephrectomies were performed on 40 patients between July 1997 and December 2002. MAIN OUTCOME MEASURES: Demographic and perioperative data including operating time, blood loss, postoperative pain score, analgesic requirement, complications, time to resume oral intake, ambulatory state, and length of hospital stay. RESULTS: Laparoscopic nephrectomy was performed for 21 solid renal masses, five transitional cell carcinomas, and 14 non-functioning kidneys. Seven (17.5%) patients had previous abdominal surgery. The mean body mass index of the patients was 23.9 kg/m(2) and the mean operating time was 229 minutes. The mean estimated blood loss was 370 mL, and two patients required conversion to open surgery because of intra-operative bleeding. Other complications include diaphragmatic injury, port-site bleeding, chyle leakage, bleeding peptic ulcer, and myocardial ischaemia. The postoperative mean analgesic requirement was 26 mg of morphine sulphate equivalent. The mean time for patients to resume oral diet and full ambulation was 1.3 and 2.8 days, respectively, and the mean length of hospital stay was 6.7 days. The mean diameter of the solid renal tumour was 4.1 cm and the surgical margins of all resected specimen for malignant tumours were negative. CONCLUSION: Laparoscopic nephrectomy is a safe and efficacious approach for resection of benign non-functioning kidneys and malignant renal tumours.published_or_final_versio

    Primary infective spondylodiscitis caused by Lactococcus garvieae and a review of human L. garvieae infections

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    We report the first case of primary infective spondylodiscitis due to Lactococcus garvieae, confirmed by 16S rRNA gene sequencing, in the absence of concomitant endocarditis in a patient with long-standing gastritis on famotidine. He responded to a 6-week course of ampicillin. The gastrointestinal tract is probably the source of infection. © 2011 The Author(s).published_or_final_versionSpringer Open Choice, 21 Feb 201

    Selective over-expression of endothelin-1 in endothelial cells exacerbates inner retinal edema and neuronal death in ischemic retina

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    The level of endothelin-1 (ET-1), a potent vasoconstrictor, was associated with retinopathy under ischemia. The effects of endothelial endothelin-1 (ET-1) over-expression in a transgenic mouse model using Tie-1 promoter (TET-1 mice) on pathophysiological changes of retinal ischemia were investigated by intraluminal insertion of a microfilament up to middle cerebral artery (MCA) to transiently block the ophthalmic artery. Two-hour occlusion and twenty-two-hour reperfusion were performed in homozygous (Hm) TET-1 mice and their non-transgenic (NTg) littermates. Presence of pyknotic nuclei in ganglion cell layer (GCL) was investigated in paraffin sections of ipsilateral (ischemic) and contralateral (non-ischemic) retinae, followed by measurement of the thickness of inner retinal layer. Moreover, immunocytochemistry of glial fibrillary acidic protein (GFAP), glutamine synthetase (GS) and aquaporin-4 (AQP4) peptides on retinal sections were performed to study glial cell reactivity, glutamate metabolism and water accumulation, respectively after retinal ischemia. Similar morphology was observed in the contralateral retinae of NTg and Hm TET-1 mice, whereas ipsilateral retina of NTg mice showed slight structural and cellular changes compared with the corresponding contralateral retina. Ipsilateral retinae of Hm TET-1 mice showed more significant changes when compared with ipsilateral retina of NTg mice, including more prominent cell death in GCL characterized by the presence of pyknotic nuclei, elevated GS immunoreactivity in Müller cell bodies and processes, increased AQP-4 immunoreactivity in Müller cell processes, and increased inner retinal thickness. Thus, over-expression of endothelial ET-1 in TET-1 mice may contribute to increased glutamate-induced neurotoxicity on neuronal cells and water accumulation in inner retina leading to edema. © 2011 Cheung et al.published_or_final_versio

    Projecting the 10-year costs of care and mortality burden of depression until 2032: a Markov modelling study developed from real-world data

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    \ua9 2024 The Authors. Background: Based on real-world data, we developed a 10-year prediction model to estimate the burden among patients with depression from the public healthcare system payer\u27s perspective to inform early resource planning in Hong Kong. Methods: We developed a Markov cohort model with yearly cycles specifically capturing the pathway of treatment-resistant depression (TRD) and comorbidity development along the disease course. Projected from 2023 to 2032, primary outcomes included costs of all-cause and psychiatric care, and secondary outcomes were all-cause deaths, years of life lived, and quality-adjusted life-years. Using the territory-wide electronic medical records, we identified 25,190 patients aged ≥10 years with newly diagnosed depression from 2014 to 2016 with follow-up until 2020 to observe the real-world time-to-event pattern, based on which costs and time-varying transition inputs were derived using negative binomial modelling and parametric survival analysis. We applied the model as both closed cohort, which studied a fixed cohort of incident patients in 2023, and open cohort, which introduced incident patients by year from 2014 to 2032. Utilities and annual new patients were from published sources. Findings: With 9217 new patients in 2023, our closed cohort model projected the 10-year cumulative costs of all-cause and psychiatric care to reach US309.0millionandUS309.0 million and US58.3 million, respectively, with 899 deaths (case fatality rate: 9.8%) by 2032. In our open cohort model, 55,849–57,896 active prevalent cases would cost more than US322.3millionandUS322.3 million and US60.7 million, respectively, with more than 943 deaths annually from 2023 to 2032. Fewer than 20% of cases would live with TRD or comorbidities but contribute 31–54% of the costs. The greatest collective burden would occur in women aged above 40, but men aged above 65 and below 25 with medical history would have the highest costs per patient-year. The key cost drivers were relevant to the early disease stages. Interpretation: A limited proportion of patients would develop TRD and comorbidities but contribute to a high proportion of costs, which necessitates appropriate attention and resource allocation. Our projection also demonstrates the application of real-world data to model long-term costs and mortality, which aid policymakers anticipate foreseeable burden and undertake budget planning to prepare for the care need in alternative scenarios. Funding: Research Impact Fund from the University Grants Committee, Research Grants Council with matching fund from the Hong Kong Association of Pharmaceutical Industry (R7007-22)

    Endothelial endothelin-1 over-expression using receptor tyrosine kinase tie-1 promoter leads to more severe vascular permeability and blood brain barrier breakdown after transient middle cerebral artery occlusion

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    Endothelin-1 (ET-1) is up-regulated in the endothelial cells and astrocytes under ischemia. Transgenic mice with astrocytic ET-1 over-expression (GET-1) showed more severe neurological deficit and larger infarct after transient middle cerebral artery occlusion (MCAO). Here, the significance of endothelial ET-1 in ischemic brain injury was investigated using transgenic mice with the endothelial ET-1 over-expression (TET-1). Increased ET-1 level was observed in the TET-1 brain infarct core after transient MCAO. ET A receptor expression was induced in the penumbra and ET A antagonist (A-147627) partially normalized the infarct volume and neurological deficit. In the infarct core of TET-1 brain, superoxide, nitrotyrosine, and gp91 phox levels were increased. TET-1 brain displayed increased matrix metalloproteinase-2 expression, water content, immunoglobulin leakage and decreased occludin level in the ipsilateral hemisphere indicative of BBB breakdown and hemispheric edema. Interestingly, AQP-4 expression was increased in the penumbra of TET-1 brain following transient MCAO leading to the water accumulation. Taken together, endothelial ET-1 over-expression and ETA receptor activation contributes to the increased oxidative stress, water accumulation and BBB breakdown after transient MCAO leading to more severe neurological deficit and increased infarct. © 2008 Elsevier B.V. All rights reserved.link_to_subscribed_fulltex
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