Myocardial fibrosis and QTc are reduced following treatment with spironolactone or amiloride in stroke survivors: a randomised placebo-controlled cross-over trial.

INTRODUCTION: Myocardial fibrosis is dysrhythmogenic and may contribute to the high incidence of cardiac death in stroke survivors, especially if they have long QTc. We tested the hypothesis that procollagen-1-carboxy terminal peptide (P1CP), a biomarker of myocardial fibrosis, might be improved following treatment with spironolactone or amiloride in stroke survivors. We also tested the hypothesis that both drugs would shorten QTc. STUDY DESIGN: randomised, double-blinded, placebo-controlled, cross-over trial (spironolactone vs. amiloride vs. placebo). Duration of Study: 3 months (1 month per drug). Primary endpoints: P1CP, QTc RESULTS: 11 stroke survivors (5 female), aged 71 ± 4, BP 139/81 mmHg ± 20/11 mmHg, completed the study. Both spironolactone and amiloride significantly reduced P1CP [Spironolactone-Placebo = -24 ug/L, 95% CI = -40 to -6.9; Amiloride-Placebo = -28 ug/L, 95% CI = -44 to -11]. Spironolactone and amiloride both shortened QTc [Spironolactone vs. Placebo=-18 ms(1/2), 95% CI = -36 to -0.55; Amiloride vs Placebo = -25 ms(1/2), 95% CI = -42 to -7.5]. CONCLUSIONS: Procollagen-1-carboxy terminal peptide was reduced following treatment with spironolactone within a month. Further, this is the first study demonstrating amiloride could also improve myocardial fibrosis. The beneficial effects of both drugs on myocardial fibrosis, coupled with their effects on raising potassium translated to a shortening of QTc. Future studies should test the hypothesis that these drugs might reduce the risk of sudden cardiac death in stroke survivors.

The cost of cerebral ischaemia.

Cerebral ischaemia is a major cause of disability and death globally and has a profoundly negative impact on the individuals it affects, those that care for them and society as a whole. The most common and familiar manifestation is stroke, 85% of which are ischaemic and which is the second leading cause of death and most common cause of complex chronic disability worldwide. Stroke survivors often suffer from long-term neurological disabilities significantly reducing their ability to integrate effectively in society with all the financial and social consequences that this implies. These difficulties cascade to their next of kin who often become caregivers and are thus indirectly burdened. A more insidious consequence of cerebral ischaemia is progressive cognitive impairment causing dementia which although less abrupt is also associated with a significant long-term disability. Globally cerebrovascular diseases are responsible for 5.4 million deaths every year (1 in 10 of total). Approximately 3% of total healthcare expenditure is attributable to cerebral ischaemia with cerebrovascular diseases costing EU healthcare systems 21 billion euro in 2003. The cost to the wider economy (including informal care and lost productivity) is even greater with stroke costing the UK 7-8 billion pound in 2005 and the US $62.7 billion in 2007. Cerebrovascular disease cost the EU 34 billion euro in 2003. From 2005 to 2050 the anticipated cost of stroke to the US economy is estimated at $2.2 trillion. Given the global scale of the problem and the enormous associated costs it is clear that there is an urgent need for advances in the prevention of cerebral ischaemia and its consequences. Such developments would result in profound benefits for both individuals and their wider societies and address one of the world's most pre-eminent public health issues.

Effect of social deprivation on mortality and the duration of hospital stay after a stroke.

BACKGROUND: We aim to assess whether social deprivation independently predicts case fatality after a stroke patient has been admitted to hospital, and to assess whether social deprivation affected duration of hospital stay. METHODS: Cohort study in a tertiary teaching hospital included consecutive patients admitted to hospital within 48 h of their stroke between 1988 and 1994. Outcome measures were case fatality at 1 year and length of hospital stay. The socioeconomic category was derived from the postcode sector of residence for the patients (Carstairs index). Cause of death was determined by data linkage to the Registrar General data for Scotland. RESULTS: 2,042 stroke patients were included. A significant age difference existed between the deprivation categories (76.0 +/- 10.9 years in the affluent cohort vs. 71.4 +/- 10.7 years in the deprived cohort). Smoking was more common in the deprived group. ECG findings and neurological score on admission were similar between the groups. No difference existed between groups for length of hospital stay (p = 0.793), and in the proportions remaining alive at 1 year (p = 0.416). When entered into a multivariate Cox regression analysis, the deprivation categories did not predict mortality. Age, sex, Philadelphia Geriatric Center Instrumental Activities of Daily Living (IADL) Scale Score, Orgogozo neurological score on admission, and ECG abnormalities were the significant predictors. CONCLUSIONS: Stroke patients living in more socially deprived areas had their strokes at an earlier age but were not at a greater risk of dying or longer hospital stay once they had been admitted to hospital.

B-type natriuretic peptide identifies silent myocardial ischaemia in stroke survivors.

OBJECTIVE: To test the hypothesis that B-type natriuretic peptide (BNP) predicts reversible myocardial ischaemia in stroke survivors who do not have chest pain or previous myocardial infarction. METHODS: 56 stroke survivors (mean (SE) age 68 (8) years) underwent tetrofosmin myocardial perfusion scanning with dipyridamole as the stressor. The degree of ischaemia was assessed by a scoring system (out of 64) by an experienced observer blinded to the results of BNP. RESULTS: In the whole cohort, BNP was significantly correlated with the degree of myocardial ischaemia on stress scanning (Spearman's r = -0.475, p < 0.001). BNP also correlated with the degree of reversible ischaemia (stress score - rest score; Spearman's r = 0.28, two tailed p = 0.049). In the cohort who did not have left ventricular systolic dysfunction (n = 44), BNP remained higher in patients with relevant myocardial ischaemia (mean (SE) BNP 20.9 pg/ml, 95% confidence interval (CI) 15.2 to 26.5 v 12.2 pg/ml, 95% CI 5.95 to 18.5; p = 0.046); 33 of the 44 patients had no chest pain or history of myocardial infarction. The relation between resting BNP and both inducible ischaemia and dipyridamole stress score remained significant (Spearman's r = 0.37 and -0.38, respectively). CONCLUSIONS: BNP correlates with the degree of reversible myocardial ischaemia in patients who do not have chest pain or a history of myocardial infarction or evidence of left ventricular systolic dysfunction. Stroke survivors with a high BNP deserve further investigations to rule out significant reversible myocardial ischaemia, in order to reduce their risk of cardiac death.

Spectrum of cardiac abnormalities associated with long QT in stroke survivors.

OBJECTIVES: To find out what spectrum of cardiac abnormalities are found in those stroke survivors who can be deemed to be at high cardiac risk by their having long QT. METHODS: 202 patients with good recovery from a cerebrovascular event occurring at least one month previously were recruited into a prospective epidemiological study. These stroke survivors underwent a battery of cardiac investigations including 12 lead ECG, echocardiography, myocardial perfusion scanning, and heart rate variability assessment. The ECGs were digitised by a single observer blinded to the blood pressure and other investigations of the patients. The maximum heart rate corrected QT interval (QTc max) in the 12 lead ECG was derived by Bazett's formula. RESULTS: Prolonged QTc max significantly correlated with increasing blood pressure, left ventricular mass index, and depressed heart rate variability. As the number of cardiac abnormalities increased, QTc max became more prolonged. CONCLUSIONS: Long QT is significantly associated with left ventricular mass index even after adjustment for both systolic and diastolic blood pressures. Long QT was also associated with the total cardiac disease burden. These two observations may explain why stroke survivors with long QTc max were at greater risk of cardiac death.

Does motor imagery training improve hand function in chronic stroke patients? A pilot study.

OBJECTIVE: To assess the efficacy of motor imagery training for arm function in chronic stroke patients. The relation between mental processes such as attentional and perceived personal control over recovery, and motor imagery was additionally investigated. DESIGN AND SUBJECTS: Twenty patients with long-term motor impairments (mean two years post stroke), were assessed before and after four weeks of training. Ten patients mentally rehearsed movements with their affected arm. Their recovery was compared with patients who performed nonmotor imagery (n =5), or who were not engaged in mental rehearsal (n=5). SETTING: Patients were recruited from the stroke database of Ninewells Hospital, Dundee. Assessment and training were performed at the patients' home. INTERVENTIONS: The motor imagery group was asked to practise daily imagining moving tokens with their affected arm. The nonmotor imagery group rehearsed visual imagery of previously seen pictures. All patients practised physically moving the tokens. MAIN MEASURES: The following variables were assessed before and after training: motor function (training task, pegboard and dynamometer), perceived locus of control, attention control and ADL independence. RESULTS: All patient groups improved on all motor tasks except the dynamometer. Improvement was greater for the motor imagery group on the training task only (average of 14% versus 6%). No effect of motor imagery training was found on perceived or attentional control. CONCLUSIONS: Motor imagery training without supervision at home may improve performance on the trained task only. The relation between movement imagery, attention and perceived personal control over recovery remained unclear.

Does a prolonged QT peak identify left ventricular hypertrophy in hypertension?

BACKGROUND: Left ventricular hypertrophy is a powerful predictor of death. Hypertensive subjects with left ventricular hypertrophy can have increased QT (end) dispersion, which is associated with cardiac death. Despite its prognostic value, QT (end) dispersion is not widely used. QTp (i.e. start of QRS to peak of T wave) is easier to measure. Therefore, we tested the hypothesis that long QT peak was associated with left ventricular hypertrophy and assessed its cost-effectiveness at diagnosing left ventricular hypertrophy. METHODS: ECGs and echocardiograms were recorded in 47 hypertensive patients. The onset of the QRS complex and peak of T wave of lead I of each subject's ECGs were digitised by one observer blind to results of the echocardiogram. Receiver-operator characteristics curves were plotted to determine the sensitivity and specificity of different cut-off values of QT peak at predicting left ventricular hypertrophy (defined as left ventricular mass index> or =134 g/m2 in male, > or =110 g/m2 in female). RESULTS: The heart-rate corrected QT peak of lead I correlated with left ventricular mass index (r=0.45, P=0.002). If all patients with a prolonged QT peak (> or =300 ms) had an echocardiogram, then no cases of left ventricular hypertrophy would be missed (100% sensitive). This novel ECG criterion not only had better positive and negative predictive values than the Sokolow-Lyon voltage criteria, but also resulted in more cost-effective resource use (< pound 370 vs. pound 1750/case of left ventricular hypertrophy detected). CONCLUSION: If the results of this small pilot study are confirmed in larger studies, then measuring QT peak of lead I may become a cost-effective way of identifying hypertensives who are likely to have echocardiographic left ventricular hypertrophy.

Cluster-randomized, controlled trial of computer-based decision support for selecting long-term anti-thrombotic therapy after acute ischaemic stroke.

BACKGROUND: Identifying the appropriate long-term anti-thrombotic therapy following acute ischaemic stroke is a challenging area in which computer-based decision support may provide assistance. AIM: To evaluate the influence on prescribing practice of a computer-based decision support system (CDSS) that provided patient-specific estimates of the expected ischaemic and haemorrhagic vascular event rates under each potential anti-thrombotic therapy. DESIGN: Cluster-randomized controlled trial. METHODS: We recruited patients who presented for a first investigation of ischaemic stroke or TIA symptoms, excluding those with a poor prognosis or major contraindication to anticoagulation. After observation of routine prescribing practice (6 months) in each hospital, centres were randomized for 6 months to either control (routine practice observed) or intervention (practice observed while the CDSS provided patient-specific information). We compared, between control and intervention centres, the risk reduction (estimated by the CDSS) in ischaemic and haemorrhagic vascular events achieved by long-term anti-thrombotic therapy, and the proportions of subjects prescribed the optimal therapy identified by the CDSS. RESULTS: Sixteen hospitals recruited 1952 subjects. When the CDSS provided information, the mean relative risk reduction attained by prescribing increased by 2.7 percentage units (95%CI -0.3 to 5.7) and the odds ratio for the optimal therapy being prescribed was 1.32 (0.83 to 1.80). Some 55% (5/9) of clinicians believed the CDSS had influenced their prescribing. CONCLUSIONS: Cluster-randomized trials provide excellent frameworks for evaluating novel clinical management methods. Our CDSS was feasible to implement and acceptable to clinicians, but did not substantially influence prescribing practice for anti-thrombotic drugs after acute ischaemic stroke.

Reversible hypertension following coeliac disease treatment: the role of moderate hyperhomocysteinaemia and vascular endothelial dysfunction.

The vascular endothelium maintains a relatively vasodilated state via the release of nitric oxide (NO), a process that could be disrupted by hyperhomocysteinaemia. Since endothelial dysfunction is associated with increased systemic vascular resistance that is the hallmark of sustained arterial hypertension, we hypothesised that in patients with both hypertension and coeliac disease with hyperhomocysteinaemia (via malabsorption of essential cofactors), treatment of the latter disease could improve blood pressure (BP) control. A single patient with proven sustained hypertension and newly-diagnosed coeliac disease had baseline and post-treatment BP and endothelial function assessed by ambulatory BP monitoring (ABPM) and brachial artery forearm occlusion plethysmography respectively. This 49 year-old woman had uncomplicated sustained hypertension proven on repeated ABPM carried out 6 weeks apart (daytime mean 151/92 mm Hg and 155/95 mm Hg), and sub-clinical coeliac disease (gluten-sensitive enteropathy). Initial assessments revealed raised homocysteine levels with low normal vitamin B(12) level. It was likely that she had impaired absorption of essential cofactors for normal homocysteine metabolism. She adhered to a gluten-free diet and was give oral iron, folate and B(6) supplementations as well as B(12) injections for 3 months. Her BP had improved by 6 months and normalised by 15 months (daytime ABPM mean 128/80 mm Hg). There was parallel restoration of normal endothelial function with normalisation of her homocysteine levels. These observations suggest that sub-clinical coeliac disease related hyperhomocysteinaemia might cause endothelial dysfunction, potentially giving rise to a reversible form of hypertension. In addition, this case study supports the notion that irrespective of aetiology, endothelial dysfunction may be the precursor of hypertension. This highlights the need to resolve co-existing vascular risk factors in patients with hypertension.

Urate predicts subsequent cardiac death in stroke survivors.

AIMS: To test the hypothesis that urate predicts cardiac death after stroke independent of conventional risk factors of atherosclerosis, creatinine and diuretic use. METHODS AND RESULTS: Serum urate concentration was measured in an unselected cohort of 354 stroke survivors who were followed-up for a median of 2.8 years. Cardiac death was the primary end-point. Urate was associated with a statistically significant threefold increase in relative risk of cardiac death even after adjustment for other conventional risk factors. In the subgroup of patients who were not on diuretics, raised urate was associated with a 12-fold significant increase in relative risk of cardiac death after adjusting for renal function and other conventional risk factors. A urate concentration of greater than 0.31 mmol. l(-1) was 78% sensitive at predicting cardiac death within 5 years after stroke, but was only 54% specific. If urate exceeded 0.38 mmol. l(-1), specificity of predicting cardiac death within 5 years after stroke was 88%. CONCLUSIONS: Elevated serum urate concentration may be used to stratify risk of future cardiac death after stroke. This appeared to be true even in stroke survivors who were not on diuretic therapy.

Serum nitrate and nitrite levels in patients with rheumatoid arthritis, ankylosing spondylitis, and osteoarthritis.

OBJECTIVE: To assess and compare serum nitrate and nitrite levels in patients with ankylosing spondylitis (AS), rheumatoid arthritis (RA), and osteoarthritis (OA). METHODS: Thirty five patients with RA, 32 patients with AS, and 36 patients with OA were entered into this study. In addition, 30 healthy volunteers acted as a control group. Concentrations of nitrate and nitrite in serum were determined by direct and indirect Griess reactions. C reactive protein and erythrocyte sedimentation rate levels were determined as markers of systemic activity of disease (SAD) in RA and AS groups. RESULTS: Serum nitrate and nitrite levels were found to be higher in patients with AS and RA than in the OA group (p<0.01). In addition, serum nitrate and nitrite levels were higher in all three groups than in the control group (p<0.01). Moreover, serum nitrate and nitrite levels were higher in patients who had SAD than in those who had not in the RA and AS groups (p<0.01 and p<0.05, respectively), and there was a correlation between serum nitrate and nitrite concentrations and SAD variables in patients with RA (Spearman's r(s)=0.414, p<0.05 and r(s)=0.408, p<0.05, respectively) and AS (r(s)=0.421, p<0.05 and r(s)=0.412, p<0.05, respectively). CONCLUSION: The findings suggest that nitrate and nitrite production is enhanced in patients with inflammatory arthritis compared with OA. In addition, serum nitrate and nitrite levels are enhanced in patients with RA, AS, and OA compared with healthy subjects. Furthermore, there is a correlation between the SAD variables and serum nitrate and nitrite levels in patients with RA and AS.

Mortality during the winter flu epidemic--two cases of death associated with self-medication.

We report two cases of mortality associated with the recent winter influenza outbreak. Both cases were associated with self-medication. In one case an elderly lady died from haemorrhagic duodenitis induced by over the counter ibuprofen. In the second case the lady died from the consequences of exceeding the recommended doses of paracetamol by combining doses of the generic product with proprietary flu-remedies and Tylex (paracetamol and codeine).

Cerebral Haemorrhage. Parenchymal intracranial haemorrhage.

While there have been substantial improvements in the management of patients with cerebral infarction and there are likely to be further improvements over the next decade, the same may not be true for cerebral haemorrhage. Diagnostic facilities and neurosurgical techniques have improved but not all patients are benefiting from these. The current literature is reviewed. Further controlled trials of the utility of modern neurosurgical techniques are urgently required as at present no therapeutic intervention holds out hope for these patients other than optimum medical management. The main focus must be on prevention.

Relationship of volume of lesion to length of hospital stay and outcome at one year in stroke patients.

The aim of this study was to investigate the relationship between the volume of lesion (VOL) in patients with stroke and the associated length of hospital stay (LOS), as well as longer-term functional outcome. Computerised tomography (CT) scans were used to measure the volume, region and type of lesion, volume being measured by planimetry. LOS and other patient details were obtained from the Dundee Stroke Database. The total LOS was associated with the VOL on univariate analysis (p = 0.004) and after adjustment for the other variables (p = 0.006) due to a larger lesion being associated with longer stay in hospital. Patient follow-up confirmed that the VOL was also highly significant when related to functional outcome measures of impairment, disability and handicap at one year, as determined by Orgogozo (p = 0.03), Barthel (p < 0.01) and Rankin scores (p < 0.01) respectively. The VOL is related to the length of stay in hospital and outcome at one year. This is of particular interest with the increasing use of thrombolysis and development of neuroprotectant agents designed to limit VOL.

Empyema of lung associated with Streptococcus milleri infection.

Empyema of the lung is a very serious illness which must be detected quickly and treated aggressively. We report an unusual case of empyema of the lung associated with a boating accident while the patient was fishing in a sea loch off the west coast of Scotland.

Which acute stroke patients with atrial fibrillation are prescribed warfarin therapy? Results from one-year's experience in Dundee.

The recommended treatment of ischaemic stroke patients with atrial fibrillation (AF) is anticoagulation therapy with warfarin sodium and if this is contraindicated then aspirin should be used. The management of patients on warfarin therapy can be complicated and there is a risk of intra-cranial haemorrhage in elderly patients. However, these are the patients who stand to gain the most benefit from this treatment and therefore increased use of warfarin for secondary prophylaxis is likely to lead to a lower rate of subsequent admissions and less morbidity. The recommended treatment for these patients has often not been fully instigated in practice. This study was carried out in order to determine whether a group of patients admitted to a teaching hospital with diagnosis of ischaemic stroke and atrial fibrillation received appropriate antithrombotic therapy. Details of patients admitted with acute stroke during 1997 were obtained from the Dundee Stroke Database and information was extracted from the relevant clinical notes. Twenty-five out of 42 patients (60%) were considered eligible for anticoagulation and 14 out of those 25 (56%) were found to be on warfarin either on admission or subsequently. Of patients aged less than 75 years, 8/10 (80%) were on warfarin, whereas only 6/15 (40%) of those aged 75 years and older were being anticoagulated.

The importance of identifying intracranial haemorrhage as a cause of transient focal neurological symptoms.

Until recently, there have been no reports of intracerebral haemorrhage presenting with transient neurological symptoms. We present two cases of intracerebral haemorrhage presenting as transient ischaemic attacks and discuss the radiological changes on early and late CT scans. It would seem justified to scan most patients presenting with TIA early to institute appropriate secondary prevention measures.

Subacute gastric volvulus--a rare cause of vomiting in the elderly.

We report a case of an important and uncommon cause of vomiting in an elderly female patient who had no previous apparent gastrointestinal problems. A diaphragmatic hernia with gastric volvulus, which presented non-specifically but was an important diagnosis to make.

The Dundee Stroke Register: experience of the first ten years.

The objective to establish a register of all patients admitted to Dundee hospitals with acute stroke has been achieved. To do this a computerised database system has been established and a prospective survey has been conducted of clinical data of patients at time of admission, with follow-up at one and three years. All patients with a WHO diagnosis of acute stroke (excluding patients with subarachnoid haemorrhage), from January 1988 have been recorded. By the end of 1998, 3222 patients had been registered. The Dundee Stroke register database is the largest in Scotland and one of the largest in the world. The establishment of the register and database has required substantial investment of resources and the collaboration of the NHS, universities and the private sector. The operation of the register has heightened interest in stroke. It also provides present and future opportunities for clinical research and audit studies and the monitoring of outcomes.