Interruption of blood flow and gas exchange to the fetus in the perinatal period, known as perinatal asphyxia, can, if significant, trigger a cascade of neuronal injury, leading on to neonatal encephalopathy(NE) and r...Interruption of blood flow and gas exchange to the fetus in the perinatal period, known as perinatal asphyxia, can, if significant, trigger a cascade of neuronal injury, leading on to neonatal encephalopathy(NE) and resultant long-term damage. While the majority of infants who are exposed to perinatal hypoxia-ischaemia will recover quickly and go on to have a completely normal survival, a proportion will suffer from an evolving clinical encephalopathy termed hypoxic-ischaemic encephalopathy(HIE) or NE if the diagnosis is unclear. Resultant complications of HIE/NE are wide-ranging and may affect the motor, sensory, cognitive and behavioural outcome of the child. The advent of therapeutic hypothermia as a neuroprotective treatment for those with moderate and severe encephalopathy has improved prognosis. Outcome prediction in these infants has changed, but is more important than ever, as hypothermia is a time sensitive intervention, with a very narrow therapeutic window. To identify those who will benefit from current and emerging neuroprotective therapies we must be able to establish the severity of their injury soon after birth. Currently available indicators such as blood biochemistry, clinical examination and electrophysiology are limited. Emerging biological and physiological markers have the potential to improve our ability to select those infants who will benefit most from intervention. Biomarkers identified from work in proteomics, metabolomics and transcriptomics as well as physiological markers such as heart rate variability, EEG analysis and radiological imaging when combined with neuroprotective measures have the potential to improve outcome in HIE/NE. The aim of this review is to give an overview of the literature in regards to short and longterm outcome following perinatal asphyxia, and to discuss the prediction of this outcome in the early hours after birth when intervention is most crucial; looking at both currently available tools and introducing novel markers.展开更多
Liver transplantation (LT) is the best treatment for end-stage hepatic failure, with an excellent survival rates over the last decade. Biliary complications after LT pose a major challenge especially with the increasi...Liver transplantation (LT) is the best treatment for end-stage hepatic failure, with an excellent survival rates over the last decade. Biliary complications after LT pose a major challenge especially with the increasing number of procured organs after circulatory death. Ischaemic cholangiopathy (IC) is a set of disorders characterized by multiple diffuse strictures affecting the graft biliary system in the absence of hepatic artery thrombosis or stenosis. It commonly presents with cholestasis and cholangitis resulting in higher readmission rates, longer length of stay, repeated therapeutic interventions, and eventually re-transplantation with consequent effects on the patient’s quality of life and increased health care costs. The pathogenesis of IC is unclear and exhibits a higher prevalence with prolonged ischaemia time, donation after circulatory death (DCD), rejection, and cytomegalovirus infection. The majority of IC occurs within 12 mo after LT. Prolonged warm ischaemic times predispose to a profound injury with a subsequently higher prevalence of IC. Biliary complications and IC rates are between 16% and 29% in DCD grafts compared to between 3% and 17% in donation after brain death (DBD) grafts. The majority of ischaemic biliary lesions occur within 30 d in DCD compared to 90 d in DBD grafts following transplantation. However, there are many other risk factors for IC that should be considered. The benefits of DCD in expanding the donor pool are hindered by the higher incidence of IC with increased rates of re-transplantation. Careful donor selection and procurement might help to optimize the utilization of DCD grafts.展开更多
Background Ischaemic reperfusion injury (IRI) is inevitable during major liver surgery. Ischaemic preconditioning (IPC) has been proven an effective intervention against hepatic IRI. Recently, it was demonstrated ...Background Ischaemic reperfusion injury (IRI) is inevitable during major liver surgery. Ischaemic preconditioning (IPC) has been proven an effective intervention against hepatic IRI. Recently, it was demonstrated that ischaemic postconditioning (IPO) provided effective cardioprotection on IRI. We evaluated the protective effects of IPO on warm/cold IRI in rat liver by a comparison with IPC and assessed the role of apoptosis in the process.Methods Warm IRI model (clamping hepatic pedicle for 30 minutes) and cold IRI model (orthotopic liver transplantation with 2 hours cold storage) were established. Each model consisted of 3 groups: (1) control group, normal warm/cold IRI; (2) IPC group, 5 minutes of ischaemia followed by 5 minutes of reperfusion twice prior to warm/cold IRI; (3) IPO group, 30 seconds of reperfusion followed by 30 seconds of reocclusion for three times after warm/cold ischaemia. The levels of serum transaminase, glucose, and γ glutamyltransferase (GGT) in bile, histopathological examination, apoptotic activity of hepatocyte, and apoptosis related protein Fas, at 3 hours after operation were compared. Survival rates one week after intervention were also compared.Results IPO and IPC protected the functions of hepatocytes and biliary epithelial cells, inhibited the hepatocellular apoptosis by preventing expression of Fas gene, and elevated the one week survival rate compared with control group in both models (P 〈0.05). IPO and IPC groups were comparable in levels of serum transaminase levels, glucose, and GGT in bile, Fas positive expression index, and one week survival. In cold ischaemic models, IPO had lower apoptotic index than IPC (P 〈0.05).Conclusion Compared with ischaemic preconditioning, ischaemic postconditioning is associated with comparable protections of rat liver from warm or cold ischaemic reperfusion injury.展开更多
Background Despite considerable improvements in the care of patients with cardiovascular disease in various populations over the last few decades, there are still limited data about long-term treatment patterns among ...Background Despite considerable improvements in the care of patients with cardiovascular disease in various populations over the last few decades, there are still limited data about long-term treatment patterns among patients with various atherosclerotic vascular conditions in China, especially the use of statin therapy. Methods Between June 2007 and October 2009, 16 860 patients aged 50-80 years with established history of atherosclerotic vascular disease (coronary heart disease (CHD), atherosclerotic cerebrovascular disease (CVD), or peripheral arterial disease (PAD)) from 51 hospitals in 14 cities of China were screened for a large randomized trial. Detailed information about current use of statins and various other treatments was recorded and analyzed by prior disease history, adjusting for various baseline characteristics. Results Among the 16 860 patients, the mean age was 63 years and 74% were male. Overall, 78% of the patients had documented CHD, 40% had CVD, 5% had PAD and 21% reported more than one condition. The median time from initial diagnosis of vascular disease to screening was 18 months. At screening, the proportions who took various treatments were 83% for antiplatelet agents, 49% for beta-blockers, 47% for statins and 28% for angiotensin-converting enzyme inhibitors. The proportion treated with statin was much higher in CHD than in CVD or PAD patients (61% vs. 10% vs. 22% respectively) and decreased significantly with time from initial diagnosis. Simvastatin (mainly 20 mg) and atorvastatin (mainly 10 mg) each accounted for about 40% of total statin use. Conclusions In urban China, there is still significant underuse of various proven secondary preventive therapies, with particularly low use of statins in patients with ischaemic stroke.展开更多
Background and purpose Transient ischaemic attack(TIA),transient symptoms with infarction(TSI)and diffusion-weighted imaging(DWI)-negative acute ischaemic stroke(AIS)share similar aetiologies but are considered to hav...Background and purpose Transient ischaemic attack(TIA),transient symptoms with infarction(TSI)and diffusion-weighted imaging(DWI)-negative acute ischaemic stroke(AIS)share similar aetiologies but are considered to have a rather benign prognosis.We intended to investigate the association between intracranial atherosclerotic stenosis(ICAS),extracranial atherosclerotic stenosis(ECAS)and the prognosis of patients with TIA,TSI and DWI-negative AIS.Methods Clinical and imaging data of eligible participants were derived from the Chinese Intracranial Atherosclerosis study,according to symptom duration,acute infarction on DWI and discharge diagnosis.Based on the severity and location of arterial atherosclerosis,we categorised the study population into four groups:no or<50% ICAS and no ECAS;≥50% ICAS but no ECAS;no or<50%ICAS with ECAS;and concurrent≥50% ICAS and ECAS.Using multivariable Cox regression models,we analysed the relationship between the severity and distribution of large artery atherosclerosis and the prognosis of TIA,TSI and DWI-negative AIS.Results A total of 806 patients were included,67.3% of whom were male.The median age of the study participants was 63 years.Patients in the concurrent≥50% ICAS and ECAS subgroup had both a significantly higher 1-year recurrence rate(adjusted HR 3.4(95%CI 1.15 to 10.04),p=0.027)and a higher risk of composite vascular events(adjusted HR 3.82(95%CI 1.50 to 9.72),p=0.005).Conclusions Concurrent ICAS and ECAS is associated with a higher possibility of 1-year recurrent stroke or composite vascular events.Large artery evaluation is necessary to assess patients with transient ischaemic symptoms or DWI-negative AIS.Progress in shortening the time interval between symptom onset and large vessel evaluation is needed.展开更多
Despite regional variations in the prevalence of coronary artery disease (CAD), men are consistently more at risk of developing and dying from CAD than women, and the gender-specific effects of sex hormones are impl...Despite regional variations in the prevalence of coronary artery disease (CAD), men are consistently more at risk of developing and dying from CAD than women, and the gender-specific effects of sex hormones are implicated in this inequality. This 'Perspectives' article reviews the current evidence regarding the cardiovascular effects of testosterone in men including an examination of the age-related decline in testosterone, the relationship between testosterone levels and coronary disease, coronary risk factors and mortality. We also review the vaso-active effects of testosterone, and discuss how these have been used in men with heart failure and angina. We discuss the 'cause' versus 'effect' controversy, regarding low testosterone levels in men with coronary heart disease, as well as concerns over the use of testosterone replacement therapy in middle aged and elderly men. The article concludes with a discussion regarding the future direction for work in this interesting area, including the relative merits of screening for, and treating hypogonadism with testosterone replacement therapy in men with heart disease.展开更多
During liver resection surgery for cancer or liver transplantation,the liver is subject to ischaemia (reduction in blood flow) followed by reperfusion (restoration of blood flow),which results in liver injury [ischemi...During liver resection surgery for cancer or liver transplantation,the liver is subject to ischaemia (reduction in blood flow) followed by reperfusion (restoration of blood flow),which results in liver injury [ischemiareperfusion (IR) or IR injury]. Modulation of IR injury can be achieved in various ways. These include hypothermia,ischaemic preconditioning (IPC) (brief cycles of ischaemia followed by reperfusion of the organ before the prolonged period of ischaemia i.e. a conditioning response),ischaemic postconditioning (conditioning after the prolonged period of ischaemia but before the reperfusion),pharmacological agents to decrease IR injury,genetic modulation of IR injury,and machine perfusion (pulsatile perfusion). Hypothermia decreases the metabolic functions and the oxygen consumption of organs. Static cold storage in University of Wisconsin solution reduces IR injury and has prolonged organ storage and improved the function of transplanted grafts. There is currently no evidence for any clinical advantage in the use of alternate solutions for static cold storage. Although experimental data from animal models suggest that IPC,ischaemic postconditioning,various pharma-cological agents,gene therapy,and machine perfusion decrease IR injury,none of these interventions can be recommended in clinical practice. This is because of the lack of randomized controlled trials assessing the safety and efficacy of ischaemic postconditioning,gene therapy,and machine perfusion. Randomized controlled trials and systematic reviews of randomized controlled trials assessing the safety and efficacy of IPC and various pharmacological agents have demonstrated biochemical or histological improvements but this has not translated to clinical benefit. Further well designed randomized controlled trials are necessary to assess the various new protective strategies in liver resection.展开更多
Background Patients with heart failure were candidates for cardiac resynchronization therapy (CRT) regardless of underlying aetiology. This study observed the effect of CRT in patients with ischaemic or nonischaemic...Background Patients with heart failure were candidates for cardiac resynchronization therapy (CRT) regardless of underlying aetiology. This study observed the effect of CRT in patients with ischaemic or nonischaemic cardiomyopathy. Methods One hundred and forty-two patients with refractory chronic heart failure and left bundle branch block received cardiac resynchronization therapy, 91 men and 51 women, average age 60 years. Left ventricular ejection fraction (LVEF) was severely depressed (mean 29%), left ventricular end diastolic diameter (LVEDD) enlarged (mean 72 mm) and QRS width was lengthened (mean 147 ms). Ninety-eight had nonischaemic cardiomyopathy and 44 had ischaemic cardiomyopathy. Results After cardiac resynchronization therapy, the heart function was significantly improved. The mean LVEF increased from 29% to 36% after pacing. In patients with nonischaemic cardiomyopathy, the LVEF was improved from 28% to 37%, and in patients with ischaemic cardiomyopathy, the LVEF was improved from 30% to 36%. No significant difference of the improvement was found between the two groups (P〉0.05). Conclusions Cardiac resynchronization therapy could significantly improve cardiac function in patients with chronic heart failure regardless of the underlying heart disease.展开更多
Background and purpose Dyslipidaemia is a major risk factor for ischaemic stroke and transient ischaemic attack(TIA).This study aimed to investigate the association between baseline low-density lipoprotein cholesterol...Background and purpose Dyslipidaemia is a major risk factor for ischaemic stroke and transient ischaemic attack(TIA).This study aimed to investigate the association between baseline low-density lipoprotein cholesterol(LDL-C)level,lipid-lowering treatment and short-term risk of new stroke in patients with a minor ischaemic stroke or TIA.Methods We derived data from the Clopidogrel in High-risk patients with Acute Non-disabling Cerebrovascular Events trial.Patients with a minor stroke or TIA were categorised by LDL-C level at baseline(<2.6 or≥2.6 mmol/L(100 mg/dL))and with or without lipid-lowering treatment after symptom onset.The primary outcome was a new ischaemic stroke at 3 months.The association of baseline LDL-C level,lowering treatment and outcomes were assessed.Results Among 3027 patients,2154(71.2%)patients had an initial LDL-C≥2.6 mmol/L,of which 1267(41.9%)received lipid-lowering treatment.Elevated LDL-C level was associated with a higher risk of new ischaemic stroke at 3 months in patients without lipid-lowering treatment(adj.HR=1.35,95%CI:1.19 to 1.53),but not in those with lipid-lowering treatment(adj.HR=0.99,95%CI:0.82 to 1.19)(p for interaction=0.007).Patients with LDL-C≥2.6 mmol/L had a numerically higher risk of ischaemic stroke(11.8%vs 8.0%,adj.HR=1.37,95%CI:0.96 to 1.96)in those without lipid-lowering treatment.For patients with LDL-C≥2.6 mmol/L,lipid-lowering treatment was associated with reduced risk of ischaemic stroke at 3 months(7.9%vs 11.8%;adj.HR=0.54,95%CI:0.39 to 0.75).Conclusions Elevated untreated baseline LDL-C level was associated with an increased short-term risk of ischaemic stroke among patients presenting with minor ischaemic stroke or TIA.There was potential benefit of lipid-lowering treatment in minor stroke or TIA patients with LDL-C≥2.6 mmol/L.Trial registration number NCT00979589.展开更多
AIM To analyse the risk factors and outcomes of delayed graft function(DGF) in patients receiving a steroid sparing protocol. METHODS Four hundred and twenty-seven recipients of deceased donor kidney transplants were ...AIM To analyse the risk factors and outcomes of delayed graft function(DGF) in patients receiving a steroid sparing protocol. METHODS Four hundred and twenty-seven recipients of deceased donor kidney transplants were studied of which 135(31.6%) experienced DGF. All patients received monoclonal antibody induction with a tacrolimus based, steroid sparing immunosuppression protocol.RESULTS Five year patient survival was 87.2% and 94.9% in the DGF and primary graft function(PGF) group respectively, P = 0.047. Allograft survival was 77.9% and 90.2% in the DGF and PGF group respectively, P < 0.001. Overall rejection free survival was no different between the DGF and PGF groups with a 1 and 5 year rejection free survival in the DGF group of 77.7% and 67.8% compared with 81.3% and 75.3% in the PGF group, P = 0.19. Patients with DGF who received IL2 receptor antibody induction were at significantly higher risk of rejection in the early post-transplant period than the group with DGF who received alemtuzumab induction. On multivariate analysis, risk factors for DGF were male recipients, recipients of black ethnicity, circulatory death donation, preformed DSA, increasing cold ischaemic time, older donor age and dialysis vintage.CONCLUSION Alemtuzumab induction may be of benefit in preventing early rejection episodes associated with DGF. Prospective trials are required to determine optimal immunotherapy protocols for patients at high risk of DGF.展开更多
Objective: This study aimed to evaluate the efficacy of trimetazidine on exercise capacity via a six-minute walk test in patients with ischaemic cardiomyopathy and also evaluate the effect of trimetazidine on left ven...Objective: This study aimed to evaluate the efficacy of trimetazidine on exercise capacity via a six-minute walk test in patients with ischaemic cardiomyopathy and also evaluate the effect of trimetazidine on left ventricular function via echocardiography in the same population. Methods: This prospective observational study, conducted at the National Institute of Cardiovascular Diseases in Dhaka, Bangladesh, enrolled 200 patients with ischaemic cardiomyopathy and a depressed left ventricular ejection fraction (LVEF Results: In this study (n = 200) of ischaemic cardiomyopathy patients, the mean age was 58 years, with 76% of the patients being male. All study subjects received GDMT (Guideline-Directed Medical Therapy) for angina and heart failure. Those who received the modified released form of trimetazidine developed lesions during the 1st and 2nd follow-ups, during which the LVEF, LVIDd, and six-minute walk distance significantly improved (p Conclusion: The findings of the present study demonstrated that the addition of modified-release trimetazidine to GDMT can improve exercise capacity and left ventricular function in patients with ischaemic cardiomyopathy.展开更多
Ischaemic reperfusion injury (IRI) is a crucial element in the pathogenesis of acute ischaemic renal failure and influences the early functional recovery and even long term survival of a transplanted kidney. It is ...Ischaemic reperfusion injury (IRI) is a crucial element in the pathogenesis of acute ischaemic renal failure and influences the early functional recovery and even long term survival of a transplanted kidney. It is generally thought that renal repair following IRI requires the replacement or regeneration of renal tubular epithelial cells that are detached or damaged.1'2 Recently, it has been reported that intravenously infused adult bone marrow-derived stem cells (BMSCs) are able to migrate to injured kidney tissue and differentiate into renal cells, potentially improving renal function.3'4 Nevertheless, the mechanisms by which bone marrow derived, stem cells promote the repair of injured kidney tissue have not been completely elucidated by animal studies.展开更多
Ischaemic heart disease(IHD)is a major cause of morbidity and mortality worldwide.While there have been major advances in this field,these patients are still a higher risk subgroup.As such,strategies to mitigate risk ...Ischaemic heart disease(IHD)is a major cause of morbidity and mortality worldwide.While there have been major advances in this field,these patients are still a higher risk subgroup.As such,strategies to mitigate risk and tailor secondary prevention measures are of the utmost relevance.Cardiac rehabilitation(CR),encompassing several domains including exercise training,cardiovascular risk factor optimization,nutritional and psychological assessments,as well as other ancillary interventions has shown to be one of the pillars in the contemporary management of patients with IHD.Indeed,CR is associated with several benefits in this population,ranging from functional capacity to improvements in outcomes.Whilst this,there are still several issues concerning the optimal application of CR which are still not fully ascertained,such as lack of referral and completion,as well as questions related to programme design(particularly among patients with multiple comorbidities).In this review,we aim at presenting a pragmatic overview on the current role of CR in the management of individuals with IHD,while also discussing some of the caveats in the current data,as well as future concepts which could help improve the uptake and personalization of this pivotal time-tested intervention.展开更多
AIM To investigate the hepatic microcirculatory changes due to Haemoxygenase(HO),effect of HO inhibition on remote ischemic preconditioning(RIPC) and modulation of CINC.METHODS Eight groups of animals were studied- Sh...AIM To investigate the hepatic microcirculatory changes due to Haemoxygenase(HO),effect of HO inhibition on remote ischemic preconditioning(RIPC) and modulation of CINC.METHODS Eight groups of animals were studied- Sham,ischemia reperfusion injury(IRI) the animals were subjected to 45 min of hepatic ischemia followed by three hours of reperfusion,RIPC(remote ischemic preconditioning) + IRI group,remote ischemic preconditioning in sham(RIPC + Sham),PDTC + IR(Pyridodithiocarbamate,HO donor),Zn PP + RIPC + IRI(Zinc protoporphyrin prior to preconditioning),IR-24(45 min of ischemia followed by 24 h of reperfusion),RIPC+IR-24(preconditioning prior to. After 3 and 24 h of reperfusion the animals were killed by exsanguination and samples were taken. RESULTS Velocity of flow(160.83 ± 12.24 μm/s),sinusoidal flow(8.42 ± 1.19) and sinusoidal perfusion index(42.12 ± 7.28) in hepatic IR were lower(P < 0.05) in comparison to RIPC and PDTC(HO inducer). RIPC increased velocity of flow(328.04 ± 19.13 μm/s),sinusoidal flow(17.75 ± 2.59) and the sinusoidal perfusion index(67.28 ± 1.82)(P < 0.05). PDTC(HO induction) reproduced the effects of RIPC in hepatic IR. PDTC restored RBC velocity(300.88 ± 22.109 μm/s),sinusoidal flow(17.66 ± 3.71) and sinusoidal perfusion(82.33 ± 3.5) to near sham levels. Zn PP(HO inhibition) reduced velocity of flow of RBC in the RIPC group(170.74 ± 13.43 μm/s and sinusoidal flow in the RIPC group(9.46 ± 1.34). Zn PP in RIPC(60.29 ± 1.82) showed a fall in perfusion only at 180 min of reperfusion. Neutrophil adhesion in IR injury is seen in both postsinusoidal venules(769.05 ± 87.48) and sinusoids(97.4 ± 7.49). Neutrophil adhesion in RIPC + IR injury is reduced in both postsinusoidal venules(219.66 ± 93.79) and sinusoids(25.69 ± 9.08)(P < 0.05). PDTC reduced neutrophil adhesion in both postsinusoidal venules(89.58 ± 58.32) and sinusoids(17.98 ± 11.01)(P < 0.05) reproducing the effects of RIPC. Zn PP(HO inhibition) increased venular(589.04 ± 144.36) and sinusoidal neutrophil adhesion in 展开更多
<strong>Background:</strong> Hypokalemia is seen on regular basis in medical emergency. The definition of hypokalemia is serum potassium level below 3.5 mmol/L, meanwhile severe hypokalemia is serum potass...<strong>Background:</strong> Hypokalemia is seen on regular basis in medical emergency. The definition of hypokalemia is serum potassium level below 3.5 mmol/L, meanwhile severe hypokalemia is serum potassium level below 2.5 mmol/L [1]. Patient with hypokalemia can present with wide range of presentation including musculoskeletal complaints from numbness to acute paralysis. Severe hypokalemia has tendency to progress to intestinal paralysis and respiratory failure. In some cases of hypokalemia, cardiovascular system can also be affected causing cardiac arrhythmias and heart failure [2]. <strong>Aim:</strong> This case report is to highlight that severe hypokalaemia can present with ECG changes mimicking acute coronary syndrome (ACS) which was fully resolved with correction of potassium level. <strong>Methods:</strong> We report a case of 84 years old Chinese man with underlying triple vessel disease presented with generalised body weakness for 2 days. ECG on arrival noted changes suggestive of ACS with ST segment depression in lead V4-V6 with first degree heart block, however patient had no ischemic symptoms and the potassium level was severe low at 1.6 mmol/L (3.5 - 5.1 mmol/L). He was correctly not treated for ACS. <strong>Outcomes:</strong> Repeated ECG post fast intravenous potassium correction noted complete resolution of the ST segment depression and first degree heart block. Patient discharged well from hospital four days later with potassium level of 3.8 mmol/L. <strong>Conclusions:</strong> Severe hypokalemia with asymptomatic ECG of ACS changes can safely be treated as a single entity clinical emergency with good resolution and no complication after normalizing potassium level.展开更多
Statins have become a cornerstone of risk modification for ischaemic heart disease patients. A number of studies have shown that they are effective and safe. However studies have observed an early benefit in terms of ...Statins have become a cornerstone of risk modification for ischaemic heart disease patients. A number of studies have shown that they are effective and safe. However studies have observed an early benefit in terms of a reduction in recurrent infarct and or death after a myocardial infarction,prior to any significant change in lipid profile. Therefore,pleiotropic mechanisms,other than lowering lipid profile alone,must account for this effect. One such proposed pleiotropic mechanism is the ability of statins to augment both number and function of endothelial progenitor cells. The ability to augment repair and maintenance of a functioning endothelium may have profound beneficial effect on vascular repair and potentially a positive impact on clinical outcomes in patients with cardiovascular disease. The following literature review will discuss issues surrounding endothelial progenitor cell(EPC) identification,role in vascular repair,factors affecting EPC numbers,the role of statins in current medical practice and their effects on EPC number.展开更多
Liver ischaemic preconditioning (IPC) is known to protect the liver from the detrimental effects of ischaemic-reperfusion injury (IRI), which contributes significantly to the morbidity and mortality following majo...Liver ischaemic preconditioning (IPC) is known to protect the liver from the detrimental effects of ischaemic-reperfusion injury (IRI), which contributes significantly to the morbidity and mortality following major liver surgery. Recent studies have focused on the role of IPC in liver regeneration, the precise mechanism of which are not completely understood. This review discusses the current understanding of the mechanism of liver regeneration and the role of IPC in this setting. Relevant articles were reviewed from the published literature using the Medline database. The search was performed using the keywords "liver", "ischaemic reperfusion', "ischaemic preconditioning", "regeneration", "hepatectomy" and "transplantation". The underlying mechanism of liver regeneration is a complex process involving the interaction of cytokines, growth factors and the metabolic demand of the liver. IPC, through various mediators, promotes liver regeneration by up-regulating growth-promoting factors and suppresses growth-inhibiting factors as well as damaging stresses. The increased understanding of the cellular mechanisms involved in IPC will enable the development of alternative treatment modalities aimed at promoting liver regeneration following major liver resection and transplantation.展开更多
Background The optimal time to commence anticoagulation in patients with atrial fibrillation(AF)after ischaemic stroke or transient ischaemic attack(TIA)is unclear,with guidelines differing in recommendations.A limita...Background The optimal time to commence anticoagulation in patients with atrial fibrillation(AF)after ischaemic stroke or transient ischaemic attack(TIA)is unclear,with guidelines differing in recommendations.A limitation of previous studies is the focus on clinically overt stroke,rather than radiologically obvious diffusion-weighted imaging ischaemic lesions.We aimed to quantify silent ischaemic lesions and haemorrhages on MRI at 1month in patients commenced on early(<4days)vs late(≥4days)anticoagulation.We hypothesised that there would be fewer ischaemic lesions and more haemorrhages in the early anticoagulant group at 1-month MRI.Methods A prospective multicentre,observational cohort study was performed at 11 Australian stroke centres.Clinical and MRI data were collected at baseline and follow-up,with blinded imaging assessment performed by two authors.Timing of commencement of anticoagulation was at the discretion of the treating stroke physician.Results We recruited 276 patients of whom 208 met the eligibility criteria.The average age was 74.2 years(SD±10.63),and 79(38%)patients were female.Median National Institute of Health Stroke Scale score was 5(IQR 1–12).Median baseline ischaemic lesion volume was 5mL(IQR 2–17).There were a greater number of new ischaemic lesions on follow-up MRI in patients commenced on anticoagulation≥4days after index event(17%vs 8%,p=0.04),but no difference in haemorrhage rates(22%vs 32%,p=0.10).Baseline ischaemic lesion volume of≤5mL was less likely to have a new haemorrhage at 1month(p=0.02).There was no difference in haemorrhage rates in patients with an initial ischaemic lesion volume of>5mL,regardless of anticoagulation timing.Conclusion Commencing anticoagulation<4days after stroke or TIA is associated with fewer ischaemic lesions at 1month in AF patients.There is no increased rate of haemorrhage with early anticoagulation.These results suggest that early anticoagulation after mild-to-moderate acute ischaemic stroke associated with AF might be safe,but randomised c展开更多
AIM:To investigate the difference in risk factors between non-arteritic anterior ischaemic optic neuropathy(NAION)and central retinal artery occlusion(CRAO)and develop a predictive diagnostic nomogram.METHODS:The stud...AIM:To investigate the difference in risk factors between non-arteritic anterior ischaemic optic neuropathy(NAION)and central retinal artery occlusion(CRAO)and develop a predictive diagnostic nomogram.METHODS:The study included 37 patients with monocular NAION,20 with monocular CRAO,and 24 with hypertension.Gender,age,and systemic diseases were recorded.Blood routine,lipids,hemorheology,carotid and brachial artery doppler ultrasound,and echocardiography were collected.The optic disc area,cup area,and cup-to-disc ratio(C/D)of the unaffected eye in the NAION and CRAO group and the right eye in the hypertension group were measured.RESULTS:The carotid artery intimal medial thickness(C-IMT)of the affected side of the CRAO group was thicker(P=0.039)and its flow-mediated dilation(FMD)was lower(P=0.049)than the NAION group.Compared with hypertension patients,NAION patients had higher whole blood reduced viscosity low-shear(WBRV-L)and erythrocyte aggregation index(EAI;P=0.045,0.037),and CRAO patients had higher index of rigidity of erythrocyte(IR)and erythrocyte deformation index(EDI;P=0.004,0.001).The optic cup and the C/D of the NAION group were smaller than the other two groups(P<0.0001).The diagnostic prediction model showed high diagnostic specificity(83.7%)and sensitivity(85.6%),which was highly related to hypertension,the C-IMT of the affected side,FMD,platelet(PLT),EAI,and C/D.CONCLUSION:CRAO patients show thicker C-IMT and worse endothelial function than NAION.NAION and CRAO may be related to abnormal hemorheology.A small cup and small C/D may be involved in NAION.The diagnostic nomogram can be used to preliminarily identify NAION and CRAO.展开更多
基金Supported by The Health Research Board CSA/2012/40a Science Foundation Ireland Research Centre Award(INFANT-12/RC/2272)
文摘Interruption of blood flow and gas exchange to the fetus in the perinatal period, known as perinatal asphyxia, can, if significant, trigger a cascade of neuronal injury, leading on to neonatal encephalopathy(NE) and resultant long-term damage. While the majority of infants who are exposed to perinatal hypoxia-ischaemia will recover quickly and go on to have a completely normal survival, a proportion will suffer from an evolving clinical encephalopathy termed hypoxic-ischaemic encephalopathy(HIE) or NE if the diagnosis is unclear. Resultant complications of HIE/NE are wide-ranging and may affect the motor, sensory, cognitive and behavioural outcome of the child. The advent of therapeutic hypothermia as a neuroprotective treatment for those with moderate and severe encephalopathy has improved prognosis. Outcome prediction in these infants has changed, but is more important than ever, as hypothermia is a time sensitive intervention, with a very narrow therapeutic window. To identify those who will benefit from current and emerging neuroprotective therapies we must be able to establish the severity of their injury soon after birth. Currently available indicators such as blood biochemistry, clinical examination and electrophysiology are limited. Emerging biological and physiological markers have the potential to improve our ability to select those infants who will benefit most from intervention. Biomarkers identified from work in proteomics, metabolomics and transcriptomics as well as physiological markers such as heart rate variability, EEG analysis and radiological imaging when combined with neuroprotective measures have the potential to improve outcome in HIE/NE. The aim of this review is to give an overview of the literature in regards to short and longterm outcome following perinatal asphyxia, and to discuss the prediction of this outcome in the early hours after birth when intervention is most crucial; looking at both currently available tools and introducing novel markers.
文摘Liver transplantation (LT) is the best treatment for end-stage hepatic failure, with an excellent survival rates over the last decade. Biliary complications after LT pose a major challenge especially with the increasing number of procured organs after circulatory death. Ischaemic cholangiopathy (IC) is a set of disorders characterized by multiple diffuse strictures affecting the graft biliary system in the absence of hepatic artery thrombosis or stenosis. It commonly presents with cholestasis and cholangitis resulting in higher readmission rates, longer length of stay, repeated therapeutic interventions, and eventually re-transplantation with consequent effects on the patient’s quality of life and increased health care costs. The pathogenesis of IC is unclear and exhibits a higher prevalence with prolonged ischaemia time, donation after circulatory death (DCD), rejection, and cytomegalovirus infection. The majority of IC occurs within 12 mo after LT. Prolonged warm ischaemic times predispose to a profound injury with a subsequently higher prevalence of IC. Biliary complications and IC rates are between 16% and 29% in DCD grafts compared to between 3% and 17% in donation after brain death (DBD) grafts. The majority of ischaemic biliary lesions occur within 30 d in DCD compared to 90 d in DBD grafts following transplantation. However, there are many other risk factors for IC that should be considered. The benefits of DCD in expanding the donor pool are hindered by the higher incidence of IC with increased rates of re-transplantation. Careful donor selection and procurement might help to optimize the utilization of DCD grafts.
文摘Background Ischaemic reperfusion injury (IRI) is inevitable during major liver surgery. Ischaemic preconditioning (IPC) has been proven an effective intervention against hepatic IRI. Recently, it was demonstrated that ischaemic postconditioning (IPO) provided effective cardioprotection on IRI. We evaluated the protective effects of IPO on warm/cold IRI in rat liver by a comparison with IPC and assessed the role of apoptosis in the process.Methods Warm IRI model (clamping hepatic pedicle for 30 minutes) and cold IRI model (orthotopic liver transplantation with 2 hours cold storage) were established. Each model consisted of 3 groups: (1) control group, normal warm/cold IRI; (2) IPC group, 5 minutes of ischaemia followed by 5 minutes of reperfusion twice prior to warm/cold IRI; (3) IPO group, 30 seconds of reperfusion followed by 30 seconds of reocclusion for three times after warm/cold ischaemia. The levels of serum transaminase, glucose, and γ glutamyltransferase (GGT) in bile, histopathological examination, apoptotic activity of hepatocyte, and apoptosis related protein Fas, at 3 hours after operation were compared. Survival rates one week after intervention were also compared.Results IPO and IPC protected the functions of hepatocytes and biliary epithelial cells, inhibited the hepatocellular apoptosis by preventing expression of Fas gene, and elevated the one week survival rate compared with control group in both models (P 〈0.05). IPO and IPC groups were comparable in levels of serum transaminase levels, glucose, and GGT in bile, Fas positive expression index, and one week survival. In cold ischaemic models, IPO had lower apoptotic index than IPC (P 〈0.05).Conclusion Compared with ischaemic preconditioning, ischaemic postconditioning is associated with comparable protections of rat liver from warm or cold ischaemic reperfusion injury.
文摘Background Despite considerable improvements in the care of patients with cardiovascular disease in various populations over the last few decades, there are still limited data about long-term treatment patterns among patients with various atherosclerotic vascular conditions in China, especially the use of statin therapy. Methods Between June 2007 and October 2009, 16 860 patients aged 50-80 years with established history of atherosclerotic vascular disease (coronary heart disease (CHD), atherosclerotic cerebrovascular disease (CVD), or peripheral arterial disease (PAD)) from 51 hospitals in 14 cities of China were screened for a large randomized trial. Detailed information about current use of statins and various other treatments was recorded and analyzed by prior disease history, adjusting for various baseline characteristics. Results Among the 16 860 patients, the mean age was 63 years and 74% were male. Overall, 78% of the patients had documented CHD, 40% had CVD, 5% had PAD and 21% reported more than one condition. The median time from initial diagnosis of vascular disease to screening was 18 months. At screening, the proportions who took various treatments were 83% for antiplatelet agents, 49% for beta-blockers, 47% for statins and 28% for angiotensin-converting enzyme inhibitors. The proportion treated with statin was much higher in CHD than in CVD or PAD patients (61% vs. 10% vs. 22% respectively) and decreased significantly with time from initial diagnosis. Simvastatin (mainly 20 mg) and atorvastatin (mainly 10 mg) each accounted for about 40% of total statin use. Conclusions In urban China, there is still significant underuse of various proven secondary preventive therapies, with particularly low use of statins in patients with ischaemic stroke.
基金grants from the National Natural Science Foundation of China(81971091 and 81901177)Beijing Hospitals Authority Youth Programme(QML20190501)+4 种基金Ministry of Science and Technology of the People’s Republic of China(2016YFC0901002,2016YFC0901001,2017YFC1310901,2017YFC1310902,2017YFC1307905,2018YFC1311700 and 2018YFC1311706)Beijing Municipal Administration of Hospitals(SML20150502)Beijing Municipal Science&Technology Commission(D171100003017002 and D151100002015003)National Science and Technology Major Project(2017ZX09304018)Beijing Tiantan Hospital(2018-YQN-1).
文摘Background and purpose Transient ischaemic attack(TIA),transient symptoms with infarction(TSI)and diffusion-weighted imaging(DWI)-negative acute ischaemic stroke(AIS)share similar aetiologies but are considered to have a rather benign prognosis.We intended to investigate the association between intracranial atherosclerotic stenosis(ICAS),extracranial atherosclerotic stenosis(ECAS)and the prognosis of patients with TIA,TSI and DWI-negative AIS.Methods Clinical and imaging data of eligible participants were derived from the Chinese Intracranial Atherosclerosis study,according to symptom duration,acute infarction on DWI and discharge diagnosis.Based on the severity and location of arterial atherosclerosis,we categorised the study population into four groups:no or<50% ICAS and no ECAS;≥50% ICAS but no ECAS;no or<50%ICAS with ECAS;and concurrent≥50% ICAS and ECAS.Using multivariable Cox regression models,we analysed the relationship between the severity and distribution of large artery atherosclerosis and the prognosis of TIA,TSI and DWI-negative AIS.Results A total of 806 patients were included,67.3% of whom were male.The median age of the study participants was 63 years.Patients in the concurrent≥50% ICAS and ECAS subgroup had both a significantly higher 1-year recurrence rate(adjusted HR 3.4(95%CI 1.15 to 10.04),p=0.027)and a higher risk of composite vascular events(adjusted HR 3.82(95%CI 1.50 to 9.72),p=0.005).Conclusions Concurrent ICAS and ECAS is associated with a higher possibility of 1-year recurrent stroke or composite vascular events.Large artery evaluation is necessary to assess patients with transient ischaemic symptoms or DWI-negative AIS.Progress in shortening the time interval between symptom onset and large vessel evaluation is needed.
文摘Despite regional variations in the prevalence of coronary artery disease (CAD), men are consistently more at risk of developing and dying from CAD than women, and the gender-specific effects of sex hormones are implicated in this inequality. This 'Perspectives' article reviews the current evidence regarding the cardiovascular effects of testosterone in men including an examination of the age-related decline in testosterone, the relationship between testosterone levels and coronary disease, coronary risk factors and mortality. We also review the vaso-active effects of testosterone, and discuss how these have been used in men with heart failure and angina. We discuss the 'cause' versus 'effect' controversy, regarding low testosterone levels in men with coronary heart disease, as well as concerns over the use of testosterone replacement therapy in middle aged and elderly men. The article concludes with a discussion regarding the future direction for work in this interesting area, including the relative merits of screening for, and treating hypogonadism with testosterone replacement therapy in men with heart disease.
文摘During liver resection surgery for cancer or liver transplantation,the liver is subject to ischaemia (reduction in blood flow) followed by reperfusion (restoration of blood flow),which results in liver injury [ischemiareperfusion (IR) or IR injury]. Modulation of IR injury can be achieved in various ways. These include hypothermia,ischaemic preconditioning (IPC) (brief cycles of ischaemia followed by reperfusion of the organ before the prolonged period of ischaemia i.e. a conditioning response),ischaemic postconditioning (conditioning after the prolonged period of ischaemia but before the reperfusion),pharmacological agents to decrease IR injury,genetic modulation of IR injury,and machine perfusion (pulsatile perfusion). Hypothermia decreases the metabolic functions and the oxygen consumption of organs. Static cold storage in University of Wisconsin solution reduces IR injury and has prolonged organ storage and improved the function of transplanted grafts. There is currently no evidence for any clinical advantage in the use of alternate solutions for static cold storage. Although experimental data from animal models suggest that IPC,ischaemic postconditioning,various pharma-cological agents,gene therapy,and machine perfusion decrease IR injury,none of these interventions can be recommended in clinical practice. This is because of the lack of randomized controlled trials assessing the safety and efficacy of ischaemic postconditioning,gene therapy,and machine perfusion. Randomized controlled trials and systematic reviews of randomized controlled trials assessing the safety and efficacy of IPC and various pharmacological agents have demonstrated biochemical or histological improvements but this has not translated to clinical benefit. Further well designed randomized controlled trials are necessary to assess the various new protective strategies in liver resection.
文摘Background Patients with heart failure were candidates for cardiac resynchronization therapy (CRT) regardless of underlying aetiology. This study observed the effect of CRT in patients with ischaemic or nonischaemic cardiomyopathy. Methods One hundred and forty-two patients with refractory chronic heart failure and left bundle branch block received cardiac resynchronization therapy, 91 men and 51 women, average age 60 years. Left ventricular ejection fraction (LVEF) was severely depressed (mean 29%), left ventricular end diastolic diameter (LVEDD) enlarged (mean 72 mm) and QRS width was lengthened (mean 147 ms). Ninety-eight had nonischaemic cardiomyopathy and 44 had ischaemic cardiomyopathy. Results After cardiac resynchronization therapy, the heart function was significantly improved. The mean LVEF increased from 29% to 36% after pacing. In patients with nonischaemic cardiomyopathy, the LVEF was improved from 28% to 37%, and in patients with ischaemic cardiomyopathy, the LVEF was improved from 30% to 36%. No significant difference of the improvement was found between the two groups (P〉0.05). Conclusions Cardiac resynchronization therapy could significantly improve cardiac function in patients with chronic heart failure regardless of the underlying heart disease.
基金supported by grants from National Key R&D Program of China(2018YFC1312903)grants from the National Natural Science Foundation of China(81971091,81870905,U20A20358)+1 种基金Beijing Hospitals Authority Youth Programme(QML20190501)grants from Beijing Municipal Science and Technology Commission(D171100003017002,Z181100001818001).
文摘Background and purpose Dyslipidaemia is a major risk factor for ischaemic stroke and transient ischaemic attack(TIA).This study aimed to investigate the association between baseline low-density lipoprotein cholesterol(LDL-C)level,lipid-lowering treatment and short-term risk of new stroke in patients with a minor ischaemic stroke or TIA.Methods We derived data from the Clopidogrel in High-risk patients with Acute Non-disabling Cerebrovascular Events trial.Patients with a minor stroke or TIA were categorised by LDL-C level at baseline(<2.6 or≥2.6 mmol/L(100 mg/dL))and with or without lipid-lowering treatment after symptom onset.The primary outcome was a new ischaemic stroke at 3 months.The association of baseline LDL-C level,lowering treatment and outcomes were assessed.Results Among 3027 patients,2154(71.2%)patients had an initial LDL-C≥2.6 mmol/L,of which 1267(41.9%)received lipid-lowering treatment.Elevated LDL-C level was associated with a higher risk of new ischaemic stroke at 3 months in patients without lipid-lowering treatment(adj.HR=1.35,95%CI:1.19 to 1.53),but not in those with lipid-lowering treatment(adj.HR=0.99,95%CI:0.82 to 1.19)(p for interaction=0.007).Patients with LDL-C≥2.6 mmol/L had a numerically higher risk of ischaemic stroke(11.8%vs 8.0%,adj.HR=1.37,95%CI:0.96 to 1.96)in those without lipid-lowering treatment.For patients with LDL-C≥2.6 mmol/L,lipid-lowering treatment was associated with reduced risk of ischaemic stroke at 3 months(7.9%vs 11.8%;adj.HR=0.54,95%CI:0.39 to 0.75).Conclusions Elevated untreated baseline LDL-C level was associated with an increased short-term risk of ischaemic stroke among patients presenting with minor ischaemic stroke or TIA.There was potential benefit of lipid-lowering treatment in minor stroke or TIA patients with LDL-C≥2.6 mmol/L.Trial registration number NCT00979589.
文摘AIM To analyse the risk factors and outcomes of delayed graft function(DGF) in patients receiving a steroid sparing protocol. METHODS Four hundred and twenty-seven recipients of deceased donor kidney transplants were studied of which 135(31.6%) experienced DGF. All patients received monoclonal antibody induction with a tacrolimus based, steroid sparing immunosuppression protocol.RESULTS Five year patient survival was 87.2% and 94.9% in the DGF and primary graft function(PGF) group respectively, P = 0.047. Allograft survival was 77.9% and 90.2% in the DGF and PGF group respectively, P < 0.001. Overall rejection free survival was no different between the DGF and PGF groups with a 1 and 5 year rejection free survival in the DGF group of 77.7% and 67.8% compared with 81.3% and 75.3% in the PGF group, P = 0.19. Patients with DGF who received IL2 receptor antibody induction were at significantly higher risk of rejection in the early post-transplant period than the group with DGF who received alemtuzumab induction. On multivariate analysis, risk factors for DGF were male recipients, recipients of black ethnicity, circulatory death donation, preformed DSA, increasing cold ischaemic time, older donor age and dialysis vintage.CONCLUSION Alemtuzumab induction may be of benefit in preventing early rejection episodes associated with DGF. Prospective trials are required to determine optimal immunotherapy protocols for patients at high risk of DGF.
文摘Objective: This study aimed to evaluate the efficacy of trimetazidine on exercise capacity via a six-minute walk test in patients with ischaemic cardiomyopathy and also evaluate the effect of trimetazidine on left ventricular function via echocardiography in the same population. Methods: This prospective observational study, conducted at the National Institute of Cardiovascular Diseases in Dhaka, Bangladesh, enrolled 200 patients with ischaemic cardiomyopathy and a depressed left ventricular ejection fraction (LVEF Results: In this study (n = 200) of ischaemic cardiomyopathy patients, the mean age was 58 years, with 76% of the patients being male. All study subjects received GDMT (Guideline-Directed Medical Therapy) for angina and heart failure. Those who received the modified released form of trimetazidine developed lesions during the 1st and 2nd follow-ups, during which the LVEF, LVIDd, and six-minute walk distance significantly improved (p Conclusion: The findings of the present study demonstrated that the addition of modified-release trimetazidine to GDMT can improve exercise capacity and left ventricular function in patients with ischaemic cardiomyopathy.
文摘Ischaemic reperfusion injury (IRI) is a crucial element in the pathogenesis of acute ischaemic renal failure and influences the early functional recovery and even long term survival of a transplanted kidney. It is generally thought that renal repair following IRI requires the replacement or regeneration of renal tubular epithelial cells that are detached or damaged.1'2 Recently, it has been reported that intravenously infused adult bone marrow-derived stem cells (BMSCs) are able to migrate to injured kidney tissue and differentiate into renal cells, potentially improving renal function.3'4 Nevertheless, the mechanisms by which bone marrow derived, stem cells promote the repair of injured kidney tissue have not been completely elucidated by animal studies.
文摘Ischaemic heart disease(IHD)is a major cause of morbidity and mortality worldwide.While there have been major advances in this field,these patients are still a higher risk subgroup.As such,strategies to mitigate risk and tailor secondary prevention measures are of the utmost relevance.Cardiac rehabilitation(CR),encompassing several domains including exercise training,cardiovascular risk factor optimization,nutritional and psychological assessments,as well as other ancillary interventions has shown to be one of the pillars in the contemporary management of patients with IHD.Indeed,CR is associated with several benefits in this population,ranging from functional capacity to improvements in outcomes.Whilst this,there are still several issues concerning the optimal application of CR which are still not fully ascertained,such as lack of referral and completion,as well as questions related to programme design(particularly among patients with multiple comorbidities).In this review,we aim at presenting a pragmatic overview on the current role of CR in the management of individuals with IHD,while also discussing some of the caveats in the current data,as well as future concepts which could help improve the uptake and personalization of this pivotal time-tested intervention.
基金Supported by Peter Samuel Grant,Royal Free NHS trust United Kingdom
文摘AIM To investigate the hepatic microcirculatory changes due to Haemoxygenase(HO),effect of HO inhibition on remote ischemic preconditioning(RIPC) and modulation of CINC.METHODS Eight groups of animals were studied- Sham,ischemia reperfusion injury(IRI) the animals were subjected to 45 min of hepatic ischemia followed by three hours of reperfusion,RIPC(remote ischemic preconditioning) + IRI group,remote ischemic preconditioning in sham(RIPC + Sham),PDTC + IR(Pyridodithiocarbamate,HO donor),Zn PP + RIPC + IRI(Zinc protoporphyrin prior to preconditioning),IR-24(45 min of ischemia followed by 24 h of reperfusion),RIPC+IR-24(preconditioning prior to. After 3 and 24 h of reperfusion the animals were killed by exsanguination and samples were taken. RESULTS Velocity of flow(160.83 ± 12.24 μm/s),sinusoidal flow(8.42 ± 1.19) and sinusoidal perfusion index(42.12 ± 7.28) in hepatic IR were lower(P < 0.05) in comparison to RIPC and PDTC(HO inducer). RIPC increased velocity of flow(328.04 ± 19.13 μm/s),sinusoidal flow(17.75 ± 2.59) and the sinusoidal perfusion index(67.28 ± 1.82)(P < 0.05). PDTC(HO induction) reproduced the effects of RIPC in hepatic IR. PDTC restored RBC velocity(300.88 ± 22.109 μm/s),sinusoidal flow(17.66 ± 3.71) and sinusoidal perfusion(82.33 ± 3.5) to near sham levels. Zn PP(HO inhibition) reduced velocity of flow of RBC in the RIPC group(170.74 ± 13.43 μm/s and sinusoidal flow in the RIPC group(9.46 ± 1.34). Zn PP in RIPC(60.29 ± 1.82) showed a fall in perfusion only at 180 min of reperfusion. Neutrophil adhesion in IR injury is seen in both postsinusoidal venules(769.05 ± 87.48) and sinusoids(97.4 ± 7.49). Neutrophil adhesion in RIPC + IR injury is reduced in both postsinusoidal venules(219.66 ± 93.79) and sinusoids(25.69 ± 9.08)(P < 0.05). PDTC reduced neutrophil adhesion in both postsinusoidal venules(89.58 ± 58.32) and sinusoids(17.98 ± 11.01)(P < 0.05) reproducing the effects of RIPC. Zn PP(HO inhibition) increased venular(589.04 ± 144.36) and sinusoidal neutrophil adhesion in
文摘<strong>Background:</strong> Hypokalemia is seen on regular basis in medical emergency. The definition of hypokalemia is serum potassium level below 3.5 mmol/L, meanwhile severe hypokalemia is serum potassium level below 2.5 mmol/L [1]. Patient with hypokalemia can present with wide range of presentation including musculoskeletal complaints from numbness to acute paralysis. Severe hypokalemia has tendency to progress to intestinal paralysis and respiratory failure. In some cases of hypokalemia, cardiovascular system can also be affected causing cardiac arrhythmias and heart failure [2]. <strong>Aim:</strong> This case report is to highlight that severe hypokalaemia can present with ECG changes mimicking acute coronary syndrome (ACS) which was fully resolved with correction of potassium level. <strong>Methods:</strong> We report a case of 84 years old Chinese man with underlying triple vessel disease presented with generalised body weakness for 2 days. ECG on arrival noted changes suggestive of ACS with ST segment depression in lead V4-V6 with first degree heart block, however patient had no ischemic symptoms and the potassium level was severe low at 1.6 mmol/L (3.5 - 5.1 mmol/L). He was correctly not treated for ACS. <strong>Outcomes:</strong> Repeated ECG post fast intravenous potassium correction noted complete resolution of the ST segment depression and first degree heart block. Patient discharged well from hospital four days later with potassium level of 3.8 mmol/L. <strong>Conclusions:</strong> Severe hypokalemia with asymptomatic ECG of ACS changes can safely be treated as a single entity clinical emergency with good resolution and no complication after normalizing potassium level.
文摘Statins have become a cornerstone of risk modification for ischaemic heart disease patients. A number of studies have shown that they are effective and safe. However studies have observed an early benefit in terms of a reduction in recurrent infarct and or death after a myocardial infarction,prior to any significant change in lipid profile. Therefore,pleiotropic mechanisms,other than lowering lipid profile alone,must account for this effect. One such proposed pleiotropic mechanism is the ability of statins to augment both number and function of endothelial progenitor cells. The ability to augment repair and maintenance of a functioning endothelium may have profound beneficial effect on vascular repair and potentially a positive impact on clinical outcomes in patients with cardiovascular disease. The following literature review will discuss issues surrounding endothelial progenitor cell(EPC) identification,role in vascular repair,factors affecting EPC numbers,the role of statins in current medical practice and their effects on EPC number.
文摘Liver ischaemic preconditioning (IPC) is known to protect the liver from the detrimental effects of ischaemic-reperfusion injury (IRI), which contributes significantly to the morbidity and mortality following major liver surgery. Recent studies have focused on the role of IPC in liver regeneration, the precise mechanism of which are not completely understood. This review discusses the current understanding of the mechanism of liver regeneration and the role of IPC in this setting. Relevant articles were reviewed from the published literature using the Medline database. The search was performed using the keywords "liver", "ischaemic reperfusion', "ischaemic preconditioning", "regeneration", "hepatectomy" and "transplantation". The underlying mechanism of liver regeneration is a complex process involving the interaction of cytokines, growth factors and the metabolic demand of the liver. IPC, through various mediators, promotes liver regeneration by up-regulating growth-promoting factors and suppresses growth-inhibiting factors as well as damaging stresses. The increased understanding of the cellular mechanisms involved in IPC will enable the development of alternative treatment modalities aimed at promoting liver regeneration following major liver resection and transplantation.
文摘Background The optimal time to commence anticoagulation in patients with atrial fibrillation(AF)after ischaemic stroke or transient ischaemic attack(TIA)is unclear,with guidelines differing in recommendations.A limitation of previous studies is the focus on clinically overt stroke,rather than radiologically obvious diffusion-weighted imaging ischaemic lesions.We aimed to quantify silent ischaemic lesions and haemorrhages on MRI at 1month in patients commenced on early(<4days)vs late(≥4days)anticoagulation.We hypothesised that there would be fewer ischaemic lesions and more haemorrhages in the early anticoagulant group at 1-month MRI.Methods A prospective multicentre,observational cohort study was performed at 11 Australian stroke centres.Clinical and MRI data were collected at baseline and follow-up,with blinded imaging assessment performed by two authors.Timing of commencement of anticoagulation was at the discretion of the treating stroke physician.Results We recruited 276 patients of whom 208 met the eligibility criteria.The average age was 74.2 years(SD±10.63),and 79(38%)patients were female.Median National Institute of Health Stroke Scale score was 5(IQR 1–12).Median baseline ischaemic lesion volume was 5mL(IQR 2–17).There were a greater number of new ischaemic lesions on follow-up MRI in patients commenced on anticoagulation≥4days after index event(17%vs 8%,p=0.04),but no difference in haemorrhage rates(22%vs 32%,p=0.10).Baseline ischaemic lesion volume of≤5mL was less likely to have a new haemorrhage at 1month(p=0.02).There was no difference in haemorrhage rates in patients with an initial ischaemic lesion volume of>5mL,regardless of anticoagulation timing.Conclusion Commencing anticoagulation<4days after stroke or TIA is associated with fewer ischaemic lesions at 1month in AF patients.There is no increased rate of haemorrhage with early anticoagulation.These results suggest that early anticoagulation after mild-to-moderate acute ischaemic stroke associated with AF might be safe,but randomised c
基金the National Natural Science Foundation of China(No.82201200).
文摘AIM:To investigate the difference in risk factors between non-arteritic anterior ischaemic optic neuropathy(NAION)and central retinal artery occlusion(CRAO)and develop a predictive diagnostic nomogram.METHODS:The study included 37 patients with monocular NAION,20 with monocular CRAO,and 24 with hypertension.Gender,age,and systemic diseases were recorded.Blood routine,lipids,hemorheology,carotid and brachial artery doppler ultrasound,and echocardiography were collected.The optic disc area,cup area,and cup-to-disc ratio(C/D)of the unaffected eye in the NAION and CRAO group and the right eye in the hypertension group were measured.RESULTS:The carotid artery intimal medial thickness(C-IMT)of the affected side of the CRAO group was thicker(P=0.039)and its flow-mediated dilation(FMD)was lower(P=0.049)than the NAION group.Compared with hypertension patients,NAION patients had higher whole blood reduced viscosity low-shear(WBRV-L)and erythrocyte aggregation index(EAI;P=0.045,0.037),and CRAO patients had higher index of rigidity of erythrocyte(IR)and erythrocyte deformation index(EDI;P=0.004,0.001).The optic cup and the C/D of the NAION group were smaller than the other two groups(P<0.0001).The diagnostic prediction model showed high diagnostic specificity(83.7%)and sensitivity(85.6%),which was highly related to hypertension,the C-IMT of the affected side,FMD,platelet(PLT),EAI,and C/D.CONCLUSION:CRAO patients show thicker C-IMT and worse endothelial function than NAION.NAION and CRAO may be related to abnormal hemorheology.A small cup and small C/D may be involved in NAION.The diagnostic nomogram can be used to preliminarily identify NAION and CRAO.