Abstract:
:Epilepsy affects 50 million persons worldwide, a third of whom continue to experience debilitating seizures despite optimum anti-epileptic drug (AED) treatment. Twelve-month remission from seizures is less likely in female patients, individuals aged 11-36 years and those with neurological insults and shorter time between first seizure and starting treatment. It has been found that the presence of multiple seizures prior to diagnosis is a risk factor for pharmacoresistance and is correlated with epilepsy type as well as intrinsic severity. The key role of neuroinflammation in the pathophysiology of resistant epilepsy is becoming clear. Our work in this area suggests that high-mobility group box 1 isoforms may be candidate biomarkers for treatment stratification and novel drug targets in epilepsy. Furthermore, transporter polymorphisms contributing to the intrinsic severity of epilepsy are providing robust neurobiological evidence on an emerging theory of drug resistance, which may also provide new insights into disease stratification. Some of the rare genetic epilepsies enable treatment stratification through testing for the causal mutation, for example SCN1A mutations in patients with Dravet's syndrome. Up to 50% of patients develop adverse reactions to AEDs which in turn affects tolerability and compliance. Immune-mediated hypersensitivity reactions to AED therapy, such as toxic epidermal necrolysis, are the most serious adverse reactions and have been associated with polymorphisms in the human leucocyte antigen (HLA) complex. Pharmacogenetic screening for HLA-B*15:02 in Asian populations can prevent carbamazepine-induced Stevens-Johnson syndrome. We have identified HLA-A*31:01 as a potential risk marker for all phenotypes of carbamazepine-induced hypersensitivity with applicability in European and other populations. In this review, we explore the currently available key stratification approaches to address the therapeutic challenges in epilepsy.
journal_name
J Intern Medjournal_title
Journal of internal medicineauthors
Walker LE,Mirza N,Yip VLM,Marson AG,Pirmohamed Mdoi
10.1111/joim.12322subject
Has Abstractpub_date
2015-02-01 00:00:00pages
218-234issue
2eissn
0954-6820issn
1365-2796journal_volume
277pub_type
杂志文章,评审abstract::A patient with undiagnosed, long-standing coeliac disease had multiple hot spots on skeletal scintigraphy, similar to those observed in malignant disease metastatic to the skeleton. A gluten-free diet corrected the pathological laboratory values, and a repeat skeletal scintigram 15 months after the first one was norma...
journal_title:Journal of internal medicine
pub_type: 杂志文章
doi:10.1111/j.1365-2796.1990.tb00252.x
更新日期:1990-10-01 00:00:00
abstract:OBJECTIVE:Therapeutic paracentesis in patients with cirrhosis is associated with a circulatory dysfunction. Intravenous albumin has been used to prevent the circulatory dysfunction; however, the use of albumin is controversial and costly. Splanchnic vasodilation is mainly responsible for circulatory dysfunction in thes...
journal_title:Journal of internal medicine
pub_type: 杂志文章,随机对照试验
doi:10.1111/j.1365-2796.2006.01654.x
更新日期:2006-07-01 00:00:00
abstract::Hypertriglyceridaemia, as defined by fasting triglyceride levels of greater than 2.8 mmol l-1, is a prevalent dyslipoproteinaemia in our population. The underlying pathophysiological mechanisms that result in elevations of plasma triglycerides are heterogeneous and, in most cases, incompletely understood. However, in ...
journal_title:Journal of internal medicine
pub_type: 杂志文章,评审
doi:10.1111/j.1365-2796.1992.tb01256.x
更新日期:1992-06-01 00:00:00
abstract:OBJECTIVES:To assess the coexistence of hypertension and diabetes, associations with cardiovascular risk factors and the achievement of current treatment goals. DESIGN:A community-based, cross-sectional, observational study. SETTING:Hypertension and diabetes outpatient clinics in primary health care, Skara, Sweden. ...
journal_title:Journal of internal medicine
pub_type: 杂志文章
doi:10.1046/j.1365-2796.1998.00286.x
更新日期:1998-03-01 00:00:00
abstract:OBJECTIVES:In this study, we explore the associations of decreased thyroid hormone levels with inflammation, wasting and survival in biochemically euthyroid patients with end-stage renal disease (ESRD). DESIGN:After exclusion of 23 patients with thyroid-stimulating hormone (TSH) values outside the normal range (0.1-4....
journal_title:Journal of internal medicine
pub_type: 杂志文章
doi:10.1111/j.1365-2796.2007.01865.x
更新日期:2007-12-01 00:00:00
abstract::The fight against doping in sports commenced as a result of the death of a Danish cyclist during the Rome Olympic Games in 1960. The International Olympic Committee (IOC) established a Medical Commission (IOC-MC) which had the task of designing a strategy to combat the misuse of drugs in Olympic Sport. Some Internatio...
journal_title:Journal of internal medicine
pub_type: 杂志文章,评审
doi:10.1111/j.1365-2796.2008.01993.x
更新日期:2008-08-01 00:00:00
abstract::In Sweden, prophylactic treatment of boys with severe haemophilia has been practised since 1958 in an attempt to convert the disease from a severe to a milder form. The present study population consisted of 60 severe haemophiliacs (52 A, 8 B), aged 3-32 years. Treatment is started when the boys are 1-2 years of age, t...
journal_title:Journal of internal medicine
pub_type: 杂志文章
doi:10.1111/j.1365-2796.1992.tb00546.x
更新日期:1992-07-01 00:00:00
abstract:OBJECTIVE:To investigate the demographic, clinical, biochemical and genotypic features of patients with erythropoietic protoporphyria (EPP) in a Swedish cohort. DESIGN:Cross-sectional questionnaire, biochemical and genetic study. SETTING:Sweden. SUBJECTS:Fifty-one Swedish individuals known in 2008 to have EPP confir...
journal_title:Journal of internal medicine
pub_type: 杂志文章
doi:10.1111/j.1365-2796.2010.02236.x
更新日期:2011-03-01 00:00:00
abstract:OBJECTIVES:There is currently widespread exposure to the toxic metal cadmium through the diet as well as through smoking, and it has been suggested that cadmium exposure may increase the risk of cardiovascular disease. Here we examined whether cadmium exposure is associated with prevalence and growth of atherosclerotic...
journal_title:Journal of internal medicine
pub_type: 杂志文章
doi:10.1111/j.1365-2796.2012.02578.x
更新日期:2012-12-01 00:00:00
abstract::Findings from preclinical and clinical studies show that vascular normalization represents a novel strategy to enhance the efficacy of and overcome the acquired resistance to anti-angiogenic therapies in cancer. Several mechanisms of tumour vessel normalization have been revealed. Amongst them, secreted class 3 semaph...
journal_title:Journal of internal medicine
pub_type: 杂志文章,评审
doi:10.1111/joim.12017
更新日期:2013-02-01 00:00:00
abstract:OBJECTIVE:To test the relationship between physical activity and physical fitness, and the relationship between these variables and the primordial risk factor blood pressure (BP). DESIGN:A cross-sectional study of all Danish pupils in the same grade at 'gymnasium' (the Danish upper secondary school). SETTING:Tests an...
journal_title:Journal of internal medicine
pub_type: 杂志文章
doi:10.1111/j.1365-2796.1994.tb00803.x
更新日期:1994-09-01 00:00:00
abstract::When and where did modern humans evolve? How did our ancestors spread over the world? Traditionally, answers to questions such as these have been sought in historical, archaeological, and fossil records. However, increasingly genetic data provide information about the evolution of our species. In this review, we focus...
journal_title:Journal of internal medicine
pub_type: 杂志文章,评审
doi:10.1046/j.1365-2796.2002.00907.x
更新日期:2002-01-01 00:00:00
abstract:BACKGROUND:Echocardiographically determined left atrioventricular plane displacement (AVPD) is strongly related to prognosis in patients with chronic heart failure and in postmyocardial infarction patients. We aimed at exploring whether AVPD, unlike ejection fraction, is related to mortality in patients with stable cor...
journal_title:Journal of internal medicine
pub_type: 杂志文章
doi:10.1046/j.1365-2796.2003.01218.x
更新日期:2003-11-01 00:00:00
abstract:OBJECTIVE:To assess the relationships between circulating levels of proinflammatory cytokines and adrenocortical hormones and leptin early after stroke. DESIGN:Blood samples were collected four times daily the first two days after stroke, twice daily the next 4 days and four times at day 7. Cognitive function and func...
journal_title:Journal of internal medicine
pub_type: 杂志文章
doi:10.1046/j.1365-2796.2000.00600.x
更新日期:2000-02-01 00:00:00
abstract::During the long history of development of haemoglobin (Hb)-based O2 carriers (HBOCs), many side effects of Hb molecules have become apparent. They imply the physiological importance of the cellular structure of red blood cells. Hb-vesicles (HbV) are artificial O2 carriers that encapsulate concentrated Hb solution with...
journal_title:Journal of internal medicine
pub_type: 杂志文章,评审
doi:10.1111/j.1365-2796.2007.01893.x
更新日期:2008-01-01 00:00:00
abstract::Cancer is a genetic disease caused by 'gain of function' mutations of oncogenes and 'loss of function' mutations of tumour suppressors and of genes involved in DNA repair mechanisms. The RET gene encodes a tyrosine kinase receptor for molecules belonging to the glial cell line-derived neurotrophic factor (GDNF) family...
journal_title:Journal of internal medicine
pub_type: 杂志文章,评审
doi:10.1046/j.1365-2796.1998.00330.x
更新日期:1998-06-01 00:00:00
abstract::Poikilothermia syndrome is a rare cause of intrinsic thermoregulatory failure. Patients with this syndrome regulate body temperature poorly, if at all. Recently, a patient was referred to us who had clinical evidence of poikilothermia syndrome, as well as long-standing multiple sclerosis. Computerized tomography and m...
journal_title:Journal of internal medicine
pub_type: 杂志文章,评审
doi:10.1046/j.1365-2796.1998.00384.x
更新日期:1998-11-01 00:00:00
abstract:OBJECTIVES:To study the relationships between plasma renin activity and metabolic cardiovascular risk factors in patients with essential hypertension. SUBJECTS AND DESIGN:Patients with uncomplicated essential hypertension (n = 36) with a diastolic blood pressure of 95-115 mmHg were studied. Assessment of plasma renin ...
journal_title:Journal of internal medicine
pub_type: 杂志文章
doi:10.1046/j.1365-2796.1996.414756000.x
更新日期:1996-01-01 00:00:00
abstract:BACKGROUND:Hyponatremia is a common feature of acute illness and associated with increased mortality. This may be explained by a stress-mediated activation of the vasopressin system with an increase in free-water reabsorption. OBJECTIVES:To investigate whether the association between hyponatremia and mortality could b...
journal_title:Journal of internal medicine
pub_type: 杂志文章,多中心研究
doi:10.1111/joim.12764
更新日期:2018-09-01 00:00:00
abstract::A case of a clinically occult ovarian carcinoma leading to subacute cor pulmonale in a 62-year-old woman is described. The patient was admitted to hospital with increasing respiratory distress. Physical examination and echocardiography showed signs of pulmonary hypertension. She died from circulatory failure. Autopsy ...
journal_title:Journal of internal medicine
pub_type: 杂志文章
doi:10.1111/j.1365-2796.1994.tb00852.x
更新日期:1994-11-01 00:00:00
abstract:OBJECTIVES:The objective of the study was to determine whether an association between diet and platelet function, plasma fibrinogen level and factor VII coagulant activity (VII:C) could be established in young subjects. DESIGN:Data on the habitual diet of the subjects were collected either by a questionnaire on food h...
journal_title:Journal of internal medicine
pub_type: 杂志文章
doi:10.1111/j.1365-2796.1995.tb00888.x
更新日期:1995-06-01 00:00:00
abstract:OBJECTIVE:We hypothesized that low presenting systolic blood pressure (SBP) predicted cardioembolic stroke aetiology. DESIGN:Active and passive surveillance were used to identify all ischaemic strokes as part of the Brain Attack Surveillance in Corpus Christi (BASIC) population-based study. Multinomial logistic regres...
journal_title:Journal of internal medicine
pub_type: 杂志文章,多中心研究
doi:10.1111/j.1365-2796.2008.02022.x
更新日期:2009-03-01 00:00:00
abstract:OBJECTIVES:A description of the clinical presentation, diagnostic procedure and mode of therapy in three patients suffering from chronic mesenteric ischaemia. DESIGN AND INTERVENTIONS:In all cases, the diagnosis was made on the basis of abdominal complaints in combination with angiographic findings. The primary treatm...
journal_title:Journal of internal medicine
pub_type: 杂志文章
doi:10.1111/j.1365-2796.1995.tb01178.x
更新日期:1995-03-01 00:00:00
abstract:OBJECTIVE:To examine the feasibility and efficacy of a multifactorial intervention programme directed towards hypercholesterolaemia, smoking, and diabetes mellitus in treated hypertensive patients after more than 3 years' follow-up and to describe the incidence of cardiovascular complications. DESIGN:Open, randomized,...
journal_title:Journal of internal medicine
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1111/j.1365-2796.1994.tb00858.x
更新日期:1994-12-01 00:00:00
abstract::This review focuses on the determinants of longevity in the industrialized world, with emphasis on results from recently established data bases. Strong evidence is now available that demonstrates that in developed countries the maximum lifespan as well as the mean lifespan have increased substantially over the past ce...
journal_title:Journal of internal medicine
pub_type: 杂志文章,评审
doi:10.1046/j.1365-2796.1996.d01-2853.x
更新日期:1996-12-01 00:00:00
abstract:BACKGROUND:The mechanisms explaining morphological electrocardiogram (ECG) changes and increased troponin T (TnT) in acute stroke are unclear. The aims of the present study were to assess the prevalence of ECG and TnT changes in acute ischaemic stroke, to investigate whether ischaemic-like ECG changes correlate to a ri...
journal_title:Journal of internal medicine
pub_type: 杂志文章
doi:10.1111/j.1365-2796.2006.01639.x
更新日期:2006-06-01 00:00:00
abstract:OBJECTIVES:The objective of this study was to examine the effects of treatment with atorvastatin, alpha-tocopherol and the combination of both, on lipoproteins and oxidative stress in dialysis patients. DESIGN AND SETTING:This double-blind randomised placebo-controlled trial was performed at the dialysis department of...
journal_title:Journal of internal medicine
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1111/j.1365-2796.2005.01484.x
更新日期:2005-05-01 00:00:00
abstract:BACKGROUND:Structural remodelling of left ventricle is a common feature in the progression of congestive heart failure (CHF). Matrix metalloproteinases (MMPs) have been directly implicated as they degrade extracellular proteins. To test the hypothesis that MMP-and its inhibitor, tissue type inhibitor of matrix metallop...
journal_title:Journal of internal medicine
pub_type: 杂志文章
doi:10.1111/j.1365-2796.2007.01823.x
更新日期:2007-09-01 00:00:00
abstract::Neutrophil granules store proteins that are critically important for the neutrophil to move from the vascular bed to tissues and to kill microorganisms. This is illustrated in nature when individual proteins are deleted due to inherited mutations of their cognate genes, and such deficiencies result in the conditions l...
journal_title:Journal of internal medicine
pub_type: 杂志文章,评审
doi:10.1111/j.1365-2796.2010.02237.x
更新日期:2010-07-01 00:00:00
abstract::Vasopressin (AVP) plays a major role in the regulation of water and sodium homeostasis by its antidiuretic action on the kidney, mediated by V2 receptors. AVP secretion is stimulated by a rise in plasma osmolality, a decline in blood volume or stress. V1a receptors are expressed in vascular smooth muscle cells, but th...
journal_title:Journal of internal medicine
pub_type: 杂志文章,评审
doi:10.1111/joim.12645
更新日期:2017-10-01 00:00:00