Hepatic encephalopathy （HE） is a common neuropsychiatric abnormality, which complicates the course of patients with liver disease and results from hepatocellular failure and/or portosystemic shunting. The manifestat...Hepatic encephalopathy （HE） is a common neuropsychiatric abnormality, which complicates the course of patients with liver disease and results from hepatocellular failure and/or portosystemic shunting. The manifestations of HE are widely variable and involve a spectrum from mild subclinical disturbance to deep coma. Research interest has focused on the role of circulating gut-derived toxins, particularly ammonia, the development of brain swelling and changes in cerebral neurotransmitter systems that lead to global CNS depression and disordered function. Until recently the direct investigation of cerebral function has been difficult in man. However, new magnetic resonance imaging （MRI） techniques provide a non-invasive means of assessment of changes in brain volume （coregistered MRI） and impaired brain function （fMRI）, while proton magnetic resonance spectroscopy （^1H MRS） detects changes in brain biochemistry, including direct measurement of cerebral osmolytes, such as myoinositol, glutamate and glutamine which govern processes intrinsic to cellular homeostasis, including the accumulation of intracellular water. The concentrations of these intracellular osmolytes alter with hyperammonaemia. MRS-detected metabolite abnormalities correlate with the severity of neuropsychiatric impairment and since MR spectra return towards normal after treatment, the technique may be of use in objective patient monitoring and in assessing the effectiveness of various treatment regimens.展开更多
Hepatocellular carcinoma (HCC) is one of the commonest cancers worldwide, particularly in parts of the developing world, and is increasing in incidence. This article reviews the current modalities employed for the dia...Hepatocellular carcinoma (HCC) is one of the commonest cancers worldwide, particularly in parts of the developing world, and is increasing in incidence. This article reviews the current modalities employed for the diagnosis of HCC, including serum markers, radiological techniques and histological evaluation, and summarises international guidelines for the diagnostic approach to HCC.展开更多
Liver metastases and hepatocellular carcinomas are two of the most common causes of cancer deaths in the world.Radiofrequency ablation(RFA) is a well recognized,effective and minimally invasive means of treating malig...Liver metastases and hepatocellular carcinomas are two of the most common causes of cancer deaths in the world.Radiofrequency ablation(RFA) is a well recognized,effective and minimally invasive means of treating malignant hepatic tumors.This article describes the use of contrast-enhanced 3D ultrasound(CE-3DUS) in the staging,targeting and follow-up of patients with liver tumors undergoing RFA.In particular,its value in the management of large hepatic lesions will be illustrated.Current limitations of CE-3DUS and future developments in the technique will also be discussed.In summary,CE-3DUS is useful in the RFA of liver tumors with improved detection and display of occult lesions and recurrence,in the assessment of lesional geometry and orientation for a more accurate planning and guidance of multiple RFA needle electrodes in large tumors and in the evaluation of residual or recurrent disease within the immediate and/or subsequent follow-up periods.展开更多
Nuclear magnetic resonance spectroscopy allows the study of cellular biochemistry and metabolism, both in the whole body in vivo and at higher magnetic field strengths in vitro. Since the technique is non-invasive and...Nuclear magnetic resonance spectroscopy allows the study of cellular biochemistry and metabolism, both in the whole body in vivo and at higher magnetic field strengths in vitro. Since the technique is non-invasive and non-selective, magnetic resonance spectroscopy methodologies have been widely applied in biochemistry and medicine. In vitro magnetic resonance spectroscopy studies of cells, body fluids and tissues have been used in medical biochemistry to investigate pathophysiologi- cal processes and more recently, the technique has been used by physicians to determine disease abnormalities in vivo. This highlighted topic illustrates the potential of in vitro magnetic resonance spectroscopy in studying the hepatobiliary system. The role of in vitro proton and phosphorus magnetic resonance spectroscopy in the study of malignant and non-malignant liver disease and bile composition studies are discussed, particularly with reference to correlative in vivo whole-body magnetic resonance spectroscopy applications. In summary, magnetic resonance spectroscopy techniques can provide non-invasive biochemical information on disease severity and pointers to underlying pathophysiological processes. Magnetic resonance spectroscopy holds potential promise as a screening tool for disease biomarkers, as well as assessing therapeutic response.展开更多
The prevalence of type 2 diabetes(T2D)has increased worldwide and doubled over the last two decades.It features among the top 10 causes of mortality and morbidity in the world.Cardiovascular disease is the leading cau...The prevalence of type 2 diabetes(T2D)has increased worldwide and doubled over the last two decades.It features among the top 10 causes of mortality and morbidity in the world.Cardiovascular disease is the leading cause of complications in diabetes and within this,heart failure has been shown to be the leading cause of emergency admissions in the United Kingdom.There are many hypotheses and well-evidenced mechanisms by which diabetic cardiomyopathy as an entity develops.This review aims to give an overview of these mechanisms,with particular emphasis on metabolic inflexibility.T2D is associated with inefficient substrate utilisation,an inability to increase glucose metabolism and dependence on fatty acid oxidation within the diabetic heart resulting in mitochondrial uncoupling,glucotoxicity,lipotoxicity and initially subclinical cardiac dysfunction and finally in overt heart failure.The review also gives a concise update on developments within clinical imaging,specifically cardiac magnetic resonance studies to characterise and phenotype early cardiac dysfunction in T2D.A better understanding of the pathophysiology involved provides a platform for targeted therapy in diabetes to prevent the development of early heart failure with preserved ejection fraction.展开更多
Objective. Motor impairment after neonatal and childhoodonset ischemic stroke (IS) is common, although the prevalence and type of hemiparesis differs between the 2 age groups. Lesion topography is an important predict...Objective. Motor impairment after neonatal and childhoodonset ischemic stroke (IS) is common, although the prevalence and type of hemiparesis differs between the 2 age groups. Lesion topography is an important predictor of hemiparesis after neonatal IS, but it is not known if the same topographic predictors of adverse motor outcome apply to childhood-onset IS. We used a consistent approach to define lesion topography and evaluate motor outcome in both age groups to (1) investigate whether early topographic predictors of hemiparesis after unilateral middle cerebral artery-territory stroke are the same in neonates and older children and (2) compare the prevalence of dystonia and loss of independent finger movements between the 2 age groups. Design. Twenty-eight patients with neonatal-onset IS (Hammersmith Hospital, London,United Kingdom)were studied together with 43 patients with childhood-onset IS (Great Ormond Street Hospital, London, United Kingdom). All patients had exclusive unilateral middle cerebral artery-territory IS. Lesion topography was studied by using the first magnetic resonance image acquired after the onset of symptoms and was coded for involvement of cerebral cortex (CC), posterior limb of the internal capsule (PLIC), basal ganglia (BG), and white matter. The primary outcome was hemiparesis, and secondary outcomes were dystonia and loss of age-appropriate independent finger movements. Results. Hemiparesis was more common after childhood-onset IS (56%) than neonatalonset IS (24%). In neonatal-onset IS, concomitant involvement of BG, CC, and PLIC predicts the development of hemiparesis (odds ratio: 99; 95%confidence interval: 5.2-1883.8), and no child with 1 or 2 of these structures involved developed hemiparesis. In contrast, in childhood-onset IS, concomitant BG, CC, and PLIC lesions tended to be associated with hemiparesis (9 of 11), but this adverse outcome was seen also among patients with 1-or 2-site involvement. However, hemiparesis was less likely if the infarction involved BG only (odds ratio: 0.162; 95%confidence interval: 0.036-0.729). Dystonia was present in 15 of 24 in the childhood-onset group with hemiparesis but was not seen after neonatal-onset IS. In both age groups upper-limb impairment was more severe than lower-limb impairment, with frequent loss of independent hand function among hemiparetic patients. Conclusions. In neonatal and childhood-onset IS, early magnetic resonance imaging provides useful prognostic information about subsequent motor outcome. There are differences in the functional response of the neuromotor system to injury between the 2 age groups that cannot be attributed to methodological differences alone.展开更多
基金Supported by grants from BUPA, the Royal College of Physicians of London and Paddington Charitable Trust, St Mary's,London. The European Association for the Study of the Liver, the British Medical Research Council (G9900178)Philips Medical Systems (Cleveland, Ohio, USA) and the United Kingdom Department of Health provided support for some of the studies outlined
文摘Hepatic encephalopathy （HE） is a common neuropsychiatric abnormality, which complicates the course of patients with liver disease and results from hepatocellular failure and/or portosystemic shunting. The manifestations of HE are widely variable and involve a spectrum from mild subclinical disturbance to deep coma. Research interest has focused on the role of circulating gut-derived toxins, particularly ammonia, the development of brain swelling and changes in cerebral neurotransmitter systems that lead to global CNS depression and disordered function. Until recently the direct investigation of cerebral function has been difficult in man. However, new magnetic resonance imaging （MRI） techniques provide a non-invasive means of assessment of changes in brain volume （coregistered MRI） and impaired brain function （fMRI）, while proton magnetic resonance spectroscopy （^1H MRS） detects changes in brain biochemistry, including direct measurement of cerebral osmolytes, such as myoinositol, glutamate and glutamine which govern processes intrinsic to cellular homeostasis, including the accumulation of intracellular water. The concentrations of these intracellular osmolytes alter with hyperammonaemia. MRS-detected metabolite abnormalities correlate with the severity of neuropsychiatric impairment and since MR spectra return towards normal after treatment, the technique may be of use in objective patient monitoring and in assessing the effectiveness of various treatment regimens.
基金Supported by The NIHR Biomedical Research Centre funding scheme and the following for authors’ funding and supportAIG is funded by a scholarship from the Egyptian Government+5 种基金SAK is supported by a grant from the Higher Education Funding Council for England (HEFCE)SDTR is funded by grants from the British Medical Research Council (MRC), London, United KingdomThe British Engineering, Physics and Science Research Council (EPSRC), Swindon, United KingdomThe Alan Morement Memorial Fund AMMF, Essex, United KingdomBroad Foundation, Los Angeles, United StatesPfizer Global Research and Development Inc, Sandwich, United Kingdom and GlaxoSmithKline, Ware, United Kingdom
文摘Hepatocellular carcinoma (HCC) is one of the commonest cancers worldwide, particularly in parts of the developing world, and is increasing in incidence. This article reviews the current modalities employed for the diagnosis of HCC, including serum markers, radiological techniques and histological evaluation, and summarises international guidelines for the diagnostic approach to HCC.
文摘Liver metastases and hepatocellular carcinomas are two of the most common causes of cancer deaths in the world.Radiofrequency ablation(RFA) is a well recognized,effective and minimally invasive means of treating malignant hepatic tumors.This article describes the use of contrast-enhanced 3D ultrasound(CE-3DUS) in the staging,targeting and follow-up of patients with liver tumors undergoing RFA.In particular,its value in the management of large hepatic lesions will be illustrated.Current limitations of CE-3DUS and future developments in the technique will also be discussed.In summary,CE-3DUS is useful in the RFA of liver tumors with improved detection and display of occult lesions and recurrence,in the assessment of lesional geometry and orientation for a more accurate planning and guidance of multiple RFA needle electrodes in large tumors and in the evaluation of residual or recurrent disease within the immediate and/or subsequent follow-up periods.
基金Supported by the Hammersmith Hospital Trustees Research Committee, the Medical Research Council, JEOL (UK) Ltd., Phil- ips Medical Systems and the Higher Education Funding Council for England
文摘Nuclear magnetic resonance spectroscopy allows the study of cellular biochemistry and metabolism, both in the whole body in vivo and at higher magnetic field strengths in vitro. Since the technique is non-invasive and non-selective, magnetic resonance spectroscopy methodologies have been widely applied in biochemistry and medicine. In vitro magnetic resonance spectroscopy studies of cells, body fluids and tissues have been used in medical biochemistry to investigate pathophysiologi- cal processes and more recently, the technique has been used by physicians to determine disease abnormalities in vivo. This highlighted topic illustrates the potential of in vitro magnetic resonance spectroscopy in studying the hepatobiliary system. The role of in vitro proton and phosphorus magnetic resonance spectroscopy in the study of malignant and non-malignant liver disease and bile composition studies are discussed, particularly with reference to correlative in vivo whole-body magnetic resonance spectroscopy applications. In summary, magnetic resonance spectroscopy techniques can provide non-invasive biochemical information on disease severity and pointers to underlying pathophysiological processes. Magnetic resonance spectroscopy holds potential promise as a screening tool for disease biomarkers, as well as assessing therapeutic response.
文摘The prevalence of type 2 diabetes(T2D)has increased worldwide and doubled over the last two decades.It features among the top 10 causes of mortality and morbidity in the world.Cardiovascular disease is the leading cause of complications in diabetes and within this,heart failure has been shown to be the leading cause of emergency admissions in the United Kingdom.There are many hypotheses and well-evidenced mechanisms by which diabetic cardiomyopathy as an entity develops.This review aims to give an overview of these mechanisms,with particular emphasis on metabolic inflexibility.T2D is associated with inefficient substrate utilisation,an inability to increase glucose metabolism and dependence on fatty acid oxidation within the diabetic heart resulting in mitochondrial uncoupling,glucotoxicity,lipotoxicity and initially subclinical cardiac dysfunction and finally in overt heart failure.The review also gives a concise update on developments within clinical imaging,specifically cardiac magnetic resonance studies to characterise and phenotype early cardiac dysfunction in T2D.A better understanding of the pathophysiology involved provides a platform for targeted therapy in diabetes to prevent the development of early heart failure with preserved ejection fraction.
文摘Objective. Motor impairment after neonatal and childhoodonset ischemic stroke (IS) is common, although the prevalence and type of hemiparesis differs between the 2 age groups. Lesion topography is an important predictor of hemiparesis after neonatal IS, but it is not known if the same topographic predictors of adverse motor outcome apply to childhood-onset IS. We used a consistent approach to define lesion topography and evaluate motor outcome in both age groups to (1) investigate whether early topographic predictors of hemiparesis after unilateral middle cerebral artery-territory stroke are the same in neonates and older children and (2) compare the prevalence of dystonia and loss of independent finger movements between the 2 age groups. Design. Twenty-eight patients with neonatal-onset IS (Hammersmith Hospital, London,United Kingdom)were studied together with 43 patients with childhood-onset IS (Great Ormond Street Hospital, London, United Kingdom). All patients had exclusive unilateral middle cerebral artery-territory IS. Lesion topography was studied by using the first magnetic resonance image acquired after the onset of symptoms and was coded for involvement of cerebral cortex (CC), posterior limb of the internal capsule (PLIC), basal ganglia (BG), and white matter. The primary outcome was hemiparesis, and secondary outcomes were dystonia and loss of age-appropriate independent finger movements. Results. Hemiparesis was more common after childhood-onset IS (56%) than neonatalonset IS (24%). In neonatal-onset IS, concomitant involvement of BG, CC, and PLIC predicts the development of hemiparesis (odds ratio: 99; 95%confidence interval: 5.2-1883.8), and no child with 1 or 2 of these structures involved developed hemiparesis. In contrast, in childhood-onset IS, concomitant BG, CC, and PLIC lesions tended to be associated with hemiparesis (9 of 11), but this adverse outcome was seen also among patients with 1-or 2-site involvement. However, hemiparesis was less likely if the infarction involved BG only (odds ratio: 0.162; 95%confidence interval: 0.036-0.729). Dystonia was present in 15 of 24 in the childhood-onset group with hemiparesis but was not seen after neonatal-onset IS. In both age groups upper-limb impairment was more severe than lower-limb impairment, with frequent loss of independent hand function among hemiparetic patients. Conclusions. In neonatal and childhood-onset IS, early magnetic resonance imaging provides useful prognostic information about subsequent motor outcome. There are differences in the functional response of the neuromotor system to injury between the 2 age groups that cannot be attributed to methodological differences alone.
