Increased Axon Initial Segment Length Results in Increased Na+ Currents in Spinal Motoneurones at Symptom Onset in the G127X SOD1 Mouse Model of Amyotrophic Lateral Sclerosis.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease preferentially affecting motoneurones. Transgenic mouse models have been used to investigate the role of abnormal motoneurone excitability in this disease. Whilst an increased excitability has repeatedly been demonstrated in vitro in neonatal and embryonic preparations from SOD1 mouse models, the results from the only studies to record in vivo from spinal motoneurones in adult SOD1 models have produced conflicting findings. Deficits in repetitive firing have been reported in G93A SOD1(high copy number) mice but not in presymptomatic G127X SOD1 mice despite shorter motoneurone axon initial segments (AISs) in these mice. These discrepancies may be due to the earlier disease onset and prolonged disease progression in G93A SOD1 mice with recordings potentially performed at a later sub-clinical stage of the disease in this mouse. To test this, and to explore how the evolution of excitability changes with symptom onset we performed in vivo intracellular recording and AIS labelling in G127X SOD1 mice immediately after symptom onset. No reductions in repetitive firing were observed showing that this is not a common feature across all ALS models. Immunohistochemistry for the Na+ channel Nav1.6 showed that motoneurone AISs increase in length in G127X SOD1 mice at symptom onset. Consistent with this, the rate of rise of AIS components of antidromic action potentials were significantly faster confirming that this increase in length represents an increase in AIS Na+ channels occurring at symptom onset in this model.

Microstructural white matter brain abnormalities in patients with idiopathic fecal incontinence.

BACKGROUND: Abnormal central nervous system processing of visceral sensation may be a part of the pathogenesis behind idiopathic fecal incontinence (IFI). Our aim was to characterize brain differences in patients with IFI and healthy controls by means of structural magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI). METHODS: In 21 female patients with IFI and 15 female healthy controls, whole-brain structural differences in gray matter volume (GMV), cortical thickness, and white matter tracts fractional anisotropy (FA) were quantified. For this purpose, we used voxel-based morphometry, surface based morphometry and tract-based spatial statistic, respectively. Furthermore, associations between structural brain characteristics and latencies of rectal sensory evoked electroencephalography potentials were determined. KEY RESULTS: Compared to healthy controls, IFI patients had significantly reduced FA values, reflecting reduced white matter tract integrity, in the left hemisphere superior longitudinal fasciculus (SLF), posterior thalamic radiation, and middle frontal gyrus (MFG), all P<.05. No differences were observed in GMV or in cortical thickness. The reduced FA values in the SLF and MFG were correlated with prolonged latencies of cortical potentials evoked by rectal stimuli (all P<.05). CONCLUSIONS & INFERENCES: This explorative study suggests that IFI patients have no macrostructural brain changes, but exhibit microstructural changes in white matter tracts relevant for sensory processing. The clinical relevance of this finding is supported by its correlations with prolonged latencies of cortical potentials evoked by rectal stimulation. This supports the theories of central nervous system changes as part of the pathogenesis in IFI patients.

Repeated Contrast Administration Is Associated With Low Risk of Postcontrast Acute Kidney Injury and Long-Term Complications in Patients With Severe Chronic Kidney Disease.

Patients with chronic kidney disease (CKD) frequently require radiographic examinations. We investigated the impact of repeated contrast administrations on short- and long-term kidney function and mortality in kidney transplantation candidates. In a prospective study, 81 predialysis transplantation candidates underwent computed tomography angiography (CTA) and invasive coronary angiography (ICA) as part of a pretransplant cardiovascular evaluation. Postcontrast plasma creatinine (P-creatinine) changes were compared with a precontrast control period. We identified postcontrast acute kidney injury (AKI) in 10 patients (13%) after CTA and in two patients (3%) after ICA. Compared with the control period, relative changes in P-creatinine were significantly higher after CTA (p < 0.001) and ICA (p < 0.01). Diabetic kidney failure (p < 0.05) and contrast dose >0.8 mL/kg (p < 0.001) were associated with increases in P-creatinine. All cases of postcontrast AKI were reversible, and we found no differences between the progression rates of the kidney failure during 12 months before and after contrast exposure (p = 0.56). In a Cox regression analysis, creatinine changes after CTA or ICA were not associated with increased need for dialysis treatment or mortality. Contrast exposure and transient postcontrast AKI did not increase the risk of accelerated CKD progression or the time to initiation of dialysis or death.

Intensive insulin therapy to non-cardiac ICU patients: a prospective study.

OBJECTIVE: Intensive insulin therapy reduced mortality in patients admitted to an intensive care unit following mainly cardiac surgery. The aim of this prospective study was to evaluate, if intensive insulin therapy could reduce mortality in medical and non-cardiac surgical patients admitted to a multidisciplinary intensive care unit. PATIENTS AND METHODS: For 6 months all adult patients, admitted to the intensive care unit, were included. Insulin was administered, if blood glucose 12 mmol L-1. For the next 6 months blood glucose level was reduced with intensive insulin therapy (aim 4.4 < BG < 6.1 mmol L-1); 271 patients were included. Patient characteristics data, APACHE II score, morbidity and mortality were recorded. RESULTS: At admission the two groups were comparable. The overall relative mortality was reduced 20% in the intensive insulin treated group (n.s.). In the intensive insulin treated group mortality was 13.1% in the medical patients and 11.2% in the surgical patients compared to 15.8% and 14.4%, respectively, in the conventional treated group (n.s.). The frequency of secondary infections was 21.5% in the intensive insulin treated group and 16.0% in the conventional treated group (n.s.). The proportion of hypoglycaemia increased from 4% to 14% (P < 0.05). CONCLUSIONS: Following intensive insulin therapy there was a trend towards reduced mortality in medical and non-cardiac surgical patients but less pronounced as in cardiac surgical patients. Intensive insulin therapy increased the frequency of hypoglycaemia. Around 4400 patients would have to be included in any future randomized study to reach significance.

Short- and long-term prognosis for very old stroke patients. The Copenhagen Stroke Study.

BACKGROUND AND PURPOSE: The very old are expected to become a growing part of the stroke population in the industrialised part of the world. The aims of this study were to evaluate clinical characteristics of patients aged 85 years or more at stroke onset and to investigate very old age as an independent predictor of short- and long-term outcome. METHODS: In the community-based Copenhagen Stroke Study we recorded admission clinical characteristics in 1197 consecutive stroke patients. Patients were stratified according to age groups on admission. Follow-up was performed at a mean of 7 years after stroke onset. By way of multiple logistic regression and survival analyses very old age was independently related to short- and long-term mortality and nursing home placement independent of other clinical characteristics. RESULTS: 16% of patients were 85 years or older at the time of stroke onset. More of the very old were women (75% versus 50%, P<0.0001), living alone (84% versus 54%, P<0.0001), had atrial fibrillation (37% versus 15%, P<0.0001), had pre-existing disability (29% versus 22%, P = 0.04), and had more severe strokes (Scandinavian Stroke Scale score 31 versus 37 points, P = 0.004). Fewer very old had hypertension (25% versus 34%, P = 0.02) and diabetes (14% versus 22%, P = 0.01). In adjusted multiple regression models, very old age predicted short-term mortality (OR 2.5; 95% CI 1.5-4.2), and discharge to nursing home or in-hospital mortality (OR 2.7; 95% CI 1.7-4.4). Five years after stroke very old age predicted mortality or nursing home placement (OR 3.9; 95% CI 2.1-7.3), and long-term mortality (HR 2.0; 95% CI 1.6-2.5). However, other factors such as onset stroke severity, pre-existing disability and atrial fibrillation were also significant independent predictors of prognosis after stroke. CONCLUSIONS: In this study very old age per se was a strong predictor of outcome and mortality after stroke. Apart from very old age, factors such as prestroke medical and functional status, and onset stroke severity should be taken into consideration when planning treatment and rehabilitation after stroke.

Admission body temperature predicts long-term mortality after acute stroke: the Copenhagen Stroke Study.

BACKGROUND AND PURPOSE: Body temperature is considered crucial in the management of acute stroke patients. Recently hypothermia applied as a therapy for stroke has been demonstrated to be feasible and safe in acute stroke patients. In the present study, we investigated the predictive role of admission body temperature to the long-term mortality in stroke patients. METHODS: We studied 390 patients with acute stroke admitted within 6 hours from stroke onset. Admission clinical characteristics (age, sex, admission stroke severity, admission blood glucose, cardiovascular risk factor profile, and stroke subtype) were recorded for patients with hypothermia (body temperature < or =37 degrees C) versus patients with hyperthermia (body temperature >37 degrees C). Univariately the mortality rates for all patients were studied by Kaplan-Meier statistics. To find independent predictors of long-term mortality for all patients, Cox proportional-hazards models were built. We included all clinical characteristics and body temperature as a continuous variable. RESULTS: Patients with hyperthermia had more severe strokes and more frequently diabetes, whereas no difference was found for the other clinical characteristics. For all patients mortality rate at 60 months after stroke was higher for patients with hyperthermia (73 per 100 cases versus 59 per 10 cases, P=0.001). When body temperature was studied in a multivariate Cox proportional-hazards model, a 1 degrees C increase of admission body temperature independently predicted a 30% relative increase (95% CI, 4% to 57%) in long-term mortality risk. For 3-month survivors we found no association between body temperature and long-term survival when studied in a multivariate Cox proportional hazard model (hazards ratio, 1.11 per 1 degrees C; 95% CI, 0.82 to 1.52). CONCLUSION: Low body temperature on admission is considered to be an independent predictor of good short-term outcome. The present study suggests that admission body temperature seems to be a major determinant even for long-term mortality after stroke. Hypothermic therapy in the early stage in which body temperature is kept low for a longer period after ictus could be a long-lasting neuroprotective measure.

Effect of hemodiafiltration and sepsis on chemotaxis of granulocytes and the release of IL-8 and IL-10.

BACKGROUND: Extracorporeal circulation, such as cardiopulmonary bypass and hemodialysis, has been associated with an activation of the immune system. Continuous veno venous hemodiafiltration (CVVHD) is used in critically ill septic patients. During CVVHD, cytokines are excreted in ultrafiltrate. When the membranes, used in CVVHD, are incubated with leukocytes in vitro a slight production of cytokines is observed. Due to the underlying disease it is difficult to investigate the effect of CVVHD in septic patients. We therefore studied the separate effect of CVVHD on the chemotaxis of granulocytes, the proliferation of lymphocytes and the release of IL-8 and IL-10 in healthy pigs compared to an endotoxin and a control group. METHODS: Thirty-one pigs were anesthetized and mechanically ventilated. CVVHD was performed in 10 pigs. Eleven pigs received an infusion of Escherichia coli endotoxin 30 microg/kg, and 10 pigs served as a control group. The chemotaxis of granulocytes was measured in an assay chamber, and the cytokines IL-8 and IL-10 with an enzyme-linked immunosorbent assay. The adhesion molecules CD18 and CD62 on lymphocytes were measured using monoclonal antibodies, and the lymphocyte proliferation was measured without stimulation and in response to mitogens. RESULTS: CVVHD was accompanied by lymphocytopenia and increased spontaneous lymphoproliferative response, but no change in adhesion molecules on lymphocytes or cytokine levels in plasma, and no decrease in the chemotaxis of granulocytes. Following endotoxin we observed a pronounced lymphocytopenia and an increased secretion of IL-8 and IL-10, a decrease in the expression of CD18 on lymphocytes and in the stimulated lymphocyte proliferation and in the chemotaxis of granulocytes. CONCLUSION: CVVHD does not, in contrast to endotoxin-induced sepsis, influence chemotaxis of granulocytes, the production of IL-8 and IL-10 or the proliferation of lymphocytes.

Carotid Doppler - costs and need after stroke or TIA.

OBJECTIVES: To estimate the need for and the costs of carotid Doppler and carotid endarterectomy after stroke or TIA in non-selected hospitalized patients. MATERIAL AND METHODS: During 25 months hospitalized patients with stroke or TIA, in whom carotid endarterectomy could be relevant, were examined with carotid Doppler. If a significant stenosis was found, they were further evaluated for surgery. Based on our results, the requirement for future carotid endarterectomy and Doppler screening was estimated, and the costs of the procedures calculated. RESULTS: Among 1351 patients 703 were screened with carotid Doppler. Forty-five had severe (70-99%) stenosis of the relevant carotid artery. Only 3 were operated on. The future costs of screening were estimated under different assumptions. CONCLUSION: Carotid endarterectomy is expensive due to the large number of patients screened with carotid Doppler per operated patient. A careful clinical selection of patients for screening is necessary.

Blood pressure in acute stroke. The Copenhagen Stroke Study.

This study examines blood pressure (BP) and independent factors related to BP in the acute phase of stroke. The study is part of the community-based Copenhagen Stroke Study. In a multivariate regression model we analyzed the impact of clinical and medical factors on admission BP. BP declined with increasing time from stroke onset with a total of 8/4 mm Hg. Independent factors related to diastolic BP were ischemic heart disease (-3.9 mm Hg), male gender (2.2 mm Hg), known hypertension prior to stroke (8.6 mm Hg), and primary hemorrhage (9.7 mm Hg). Independent factors related to systolic BP were age (3.6 mm Hg/10-year increase), atrial fibrillation (-7.2 mm Hg), ischemic heart disease (-6.0 mm Hg), intracerebral hemorrhage (13.3 mm Hg), and known hypertension prior to stroke (16.3 mm Hg). No independent relations were seen between BP and diabetes, claudication, previous stroke, smoking, daily alcohol consumption, initial stroke severity and lesion size. The increase in BP in the acute phase of stroke is a uniform response to the ischemic event per se. BP is not related to stroke severity. Several factors are independently related to the BP level in acute stroke. The clinical significance of this is yet to be tested, but these factors may contribute to the seemingly complex relation between BP and outcome.

Partial unilateral ureteropelvic junction obstruction induced in 2-week-old piglets.

PURPOSE: We examined effects on kidney function and morphology of a partial ureteropelvic junction obstruction induced late in the postnatal nephrogenesis period of the pig. We compared the results to a similar study on pigs with obstruction induced early in the nephrogenesis period. MATERIALS AND METHODS: A total of 20 14-day-old pigs were included in the study. Fifteen animals were randomized to partial unilateral obstruction and 5 were sham operated. Kidney function and morphology were analyzed regarding glomerular filtration rate, renographic functional share and total kidney volume at the age of 4, 12 and 24 weeks. RESULTS: At age 4 weeks hydronephrosis was found in all obstructed kidneys included in the study. Four obstructed kidneys had renographic functional share 40% or greater and 1 deteriorated to less than 40% at 24 weeks. A total of 11 obstructed kidneys had a functional share less than 40%, 5 increased to a share greater than 40% at age 24 weeks and 3 had decreasing share from age 4 to 24 weeks. Single kidney glomerular filtration rate of the contralateral kidneys was significantly increased at all ages. Volume of the contralateral kidney was significantly increased at age 4 and 12 weeks. CONCLUSIONS: The variability and course of renographic functional share in kidneys subjected to partial obstruction at age 2 weeks was similar to findings obtained in pigs obstructed at age 2 days. In contrast to these our study showed compensatory increase in function and size of the contralateral kidney, suggesting that contralateral compensation is an ability gained late in the nephrogenesis period.

Manual and oral apraxia in acute stroke, frequency and influence on functional outcome: The Copenhagen Stroke Study.

OBJECTIVES: To determine the frequency of manual and oral apraxia in acute stroke and to examine the influence of these symptoms on functional outcome. DESIGN: Seven hundred seventy six unselected, acute stroke patients who were admitted within seven days of stroke onset with unimpaired consciousness were included. If possible, the patients were assessed for manual and oral apraxia on acute admission. Neurologic stroke severity including aphasia was assessed with the Scandinavian Stroke Scale, and activities of daily living function was assessed with the Barthel Index. All patients completed their rehabilitation in the same large stroke unit. RESULTS: Six hundred eighteen patients could cooperate with the apraxia assessments. Manual apraxia was found in 7% of subjects (10% in left and 4% in right hemispheric stroke; chi2 = 9.0; P = 0.003). Oral apraxia was found in 6% (9% in left and 4% in right hemispheric stroke; chi2 = 5.4; P = 0.02). Both manual and oral apraxia were related to increasing stroke severity, and manual, but not oral, apraxia was associated with increasing age. There was no gender difference in frequency of apraxia. Patients with either type of apraxia had temporal lobe involvement more often than patients without. When analyzed with multiple linear and logistic regression analyses, neither manual nor oral apraxia had any independent influence on functional outcome. CONCLUSION: Apraxia is significantly less frequent in unselected patients with acute stroke than has previously been assumed and has no independent negative influence on functional outcome.

Potentially reversible factors during the very acute phase of stroke and their impact on the prognosis: is there a large therapeutic potential to be explored?

In the Copenhagen Stroke Study, we evaluated the combined impact on stroke outcome of potentially treatable factors such as acute body temperature, blood glucose, and stroke in progression. The patients were stratified into two groups: (1) patients with 'good' prognostic parameters (body temperature on admission < or = 37.0 degrees C and plasma glucose on admission < or = 6.5 mmol/l and who did not develop stroke in progression) and (2) patients with correspondingly 'poor' prognostic parameters. A poor outcome was observed in 4% of the patients with good prognostic parameters versus in 49% of the patients with poor prognostic parameters (p < 0.01). In the multivariate analysis which also included stroke severity, blood glucose contributed significantly to poor outcome with an odds ratio (OR) of 1.2/1.0 mmol/l increase, body temperature with an OR of 2.2/1 degrees C increase, and stroke in progression with an OR of 2.9. However, the combined effect of all three factors was more than additive with an OR of 10.0 (95% CI 1.5-56; p < 0.01). We have shown that in human stroke a strong and more than additive association exists between potentially reversible parameters and outcome. Intervention trials can prove whether these marked relations are causal.

Renal function outcome in unilateral hydronephrosis in newborn pigs. II. Function and volume of contralateral kidneys.

PURPOSE: We evaluated the compensatory response of contralateral kidney growth and function in pigs with unilateral hydronephrosis. MATERIALS AND METHODS: Unilateral partial ureteral obstruction causing severe hydronephrosis was induced at age 2 days in 12 piglets, while 10 underwent sham operation. At ages 4, 12 and 24 weeks single kidney function was assessed using 99mtechnetium diethylenetriaminepentaacetic acid differential uptake on renography combined with the glomerular filtration rate estimated from the plasma clearance of 99mtechnetium diethylenetriaminepentaacetic acid. Kidney size was measured in parallel by magnetic resonance imaging. RESULTS: At 4 weeks the glomerular filtration rate and volume of the contralateral kidneys did not differ from those in controls, although obstructed kidney function was significantly decreased. At 12 weeks the mean glomerular filtration rate plus or minus standard error of mean of the contralateral kidneys significantly increased to 1.60 +/- 0.11 versus 1.33 +/- 0.11 ml. per minute per kg. (p <0. 05), whereas kidney volume did not differ from that in sham operated controls. At 24 weeks the glomerular filtration rate and volume of the contralateral kidneys did not differ from those in controls. Glomerular filtration rate and volume of the contralateral kidneys did not correlate at 4 weeks but they correlated at 12 and 24 weeks (r = 0.94 and 0.89, respectively). CONCLUSIONS: Initially kidneys contralateral to obstructed kidneys with decreased function had no increased growth or function. Furthermore, function and volume of the contralateral kidneys were not associated at the early age. Thus, the results of our study imply that determining the size (growth) or function of the contralateral kidney at an early age does not predict function decrease in a partially obstructed kidney in this pig model.

Early infection and prognosis after acute stroke: the Copenhagen Stroke Study.

BACKGROUND AND PURPOSE: Infection is a frequent complication in the early course of acute stroke and may adversely affect stroke outcome. In the present study, we investigate early infection developing in patients within 3 days of admission to the hospital and its independent relation to recovery and stroke outcome. In addition, we identify predictors for early infections, infection subtypes, and their relation to initial stroke severity. METHODS: In the community-based Copenhagen Stroke Study, 1,156 unselected patients were examined for early infection. Stroke severity was assessed with the Scandinavian Stroke Scale (SSS) on admission and at discharge. Multiple logistic and linear regression analyses were used to determine independent relations to early infection. Relevant stroke risk factors, admission stroke severity, and body temperature were included in the analysis. RESULTS: Of the subjects studied, 19.4% developed early infection. In women, 68% of the early infections were urinary tract infections, and in men, 49% of the early infections were pneumonias. Independent predictors of early infection were advanced age (OR per 10 years, 1.24; 95% CI, 1.02-1.64), female gender (OR, 2.0; 95% CI, 1.3-3.0), and decreased SSS score on admission (OR per 10 points, 0.69; 95% CI, 0.62-0.78). The presence of early infection prolonged hospital stay by a mean of 9.3 days (P < .0001) but not death during hospital stay (P = .78), stroke severity at discharge (P = .32), or rate of discharge to nursing home (P = .17). CONCLUSION: Advanced age, female gender, and increased stroke severity independently predict development of early infection. The present study indicates that early infection does not influence outcome in acute stroke patients per se, but it delays patient discharge from the hospital.

Feasibility and safety of inducing modest hypothermia in awake patients with acute stroke through surface cooling: A case-control study: the Copenhagen Stroke Study.

BACKGROUND AND PURPOSE: Hypothermia reduces neuronal damage in animal stroke models. Whether hypothermia is neuroprotective in patients with acute stroke remains to be clarified. In this case-control study, we evaluated the feasibility and safety of inducing modest hypothermia by a surface cooling method in awake patients with acute stroke. METHODS: We prospectively included 17 patients (cases) with stroke admitted within 12 hours from stoke onset (mean 3.25 hours). They were given hypothermic treatment for 6 hours by the "forced air" method, a surface cooling method that uses a cooling blanket with a flow of cool air (10 degrees C). Pethidine was given to treat compensatory shivering. Cases were compared with 56 patients (controls) from the Copenhagen Stroke Study matched for age, gender, initial stroke severity, body temperature on admission, and time from stroke onset to admission. Blood cytology, biochemistry, ECGs, and body temperature were monitored during hypothermic treatment. Multiple regression analyses on outcome were performed to examine the safety of hypothermic therapy. RESULTS: Body temperature decreased from t(0)=36.8 degrees C to t(6)=35.5 degrees C (P:<0.001), and hypothermia was present until 4 hours after therapy (t(0)=36.8 degrees C versus t(10)=36.5 degrees C; P:=0.01). Mortality at 6 months after stroke was 12% in cases versus 23% in controls (P:=0. 50). Final neurological impairment (Scandinavian Stroke Scale score at 6 months) was mean 42.4 points in cases versus 47.9 in controls (P:=0.21). Hypothermic therapy was not a predictor of poor outcome in the multivariate analyses. CONCLUSIONS: Modest hypothermia can be achieved in awake patients with acute stroke by surface cooling with the "forced air" method, in combination with pethidine to treat shivering. It was not associated with a poor outcome. We suggest a large, randomized clinical trial to test the possible beneficial effect of induced modest hypothermia in unselected patients with stroke.

[Treatment and rehabilitation in an apoplexy unit increases the 5-year survival]. / Behandling og rehabilitering på apopleksiafsnit øger 5-års-overlevelsen.

Treatment of stroke patients in specialised stroke units has become more frequent, but the longterm effect of this treatment has not been determined. In this prospective, community-based study of 1241 unselected acute stroke patients we compared outcome between patients geographically randomised to treatment in a stroke unit or in a general neurological/medical ward, from the time of acute admission to the end of rehabilitation. Baseline characteristics were comparable between the two treatment groups regarding age, sex, marital status, pre-stroke residence, and stroke severity. Patients treated in the stroke unit had higher comorbidity with regard to hypertension and diabetes. Multivariate linear and logistic regression analyses were applied to estimate the independent influence of stroke unit treatment on outcome. Stroke unit treatment significantly reduced not only initial mortality, but also mortality within five years from stroke onset. The relative risk of dying within the first five years from stroke was reduced by 40%, p < 0.01. Treatment and rehabilitation of unselected stroke patients in a stroke unit reduces initial mortality, discharge rate to nursing home, reduces cost of treatment, and improves longterm survival up to five years after stroke.

The effect of CVVHD and endotoxin on the oxidative burst, adhesion molecules and distribution in tissues of granulocytes.

OBJECTIVE: Extracorporeal circulation, such as cardiopulmonary bypass and haemodialysis, has been associated with an activation of the immune system, especially the granulocytes. Continuous veno-venous haemodiafiltration (CVVHD) is used in critically ill septic patients. During CVVHD cytokines are excreted in the ultrafiltrate. But when the membranes used in CVVHD are cultured with granulocytes, the granulocytes are slightly activated. This effect is potentiated by endotoxin. We therefore, in vivo, compared the effect on granulocyte activation of CVVHD with an endotoxin group and a control group. METHODS: Thirty-one pigs were anaesthetized and mechanically ventilated. In ten pigs CVVHD was performed. Eleven pigs received an infusion of Escherichia coli endotoxin 30 mu/kg(-1) and ten pigs served as a control group. The adhesion molecules CD18 and CD62L were measured using monoclonal antibodies. The oxidative burst activity was assayed as superoxide dismutase-inhibitory reduction of cytochrome c. The number of granulocytes in peripheral blood and in the lungs and liver were counted. RESULTS: The infusion of endotoxin was followed by granulocytopenia, reduced oxidative burst activity, increased expression of CD18 and decreased expression of CD62L on granulocytes. Accumulation of granulocytes in liver and lung tissue was also noted in this group. CVVHD was only associated with a non-significant decrease in CD62L expression on granulocytes. It did not affect any of the other measured immunological parameters. CONCLUSION: In contrast to endotoxin-induced sepsis, the granulocytes were not activated during CVVHD.

Outcome measures in acute stroke trials: a systematic review and some recommendations to improve practice.

BACKGROUND: There is little consistency in the measurement of outcome in acute stroke trials, and this may complicate interpretation of the results and reduce the likelihood of detecting worthwhile drug effects. This study aims to investigate empirically the measures used to date and to give recommendations for future studies. SUMMARY OF COMMENT: A systematic review of all published randomized studies of acute stroke drug intervention was undertaken, and the measures used were recorded. Fifty-one studies involving 57 214 subjects were identified. These studies used 14 different measures of impairment, 11 different measures of activity, 1 measure of "quality of life," and 8 miscellaneous other measures. Timing of outcome assessments varied from 1 week to 1 year, with the modal time being 3 months. Many studies used ordinal measures but dichotomized results for analysis. Of the 51 studies included in the review, only 21 demonstrated benefit with the defined primary outcome measure. In several studies, however, post hoc analysis using varied outcome measures or varied cut points for dichotomizing outcomes resulted in positive results, whereas the primary study analysis failed to do so. CONCLUSIONS: There is no consensus on the level of outcome to be used, the method of measurement to be used, or the most appropriate timing of the assessment. It is recommended that future studies should include extended/instrumental activities and advanced mobility as components of the primary outcome measure, with outcome assessment being undertaken at 6 months. New initiatives in developing stroke-specific outcomes may address some of the current problems in the assessment of stroke outcomes

Prediction of walking function in stroke patients with initial lower extremity paralysis: the Copenhagen Stroke Study.

OBJECTIVES: The majority of stroke patients with initial leg paralysis do not regain independent walking. We characterize the minority who, despite initial leg paralysis, regained independent walking. DESIGN: Consecutive and community based. SETTING: A stroke unit receiving all stroke patients from a well-defined community. PATIENTS: A total of 859 acute stroke patients; 157 (15%) initially had leg paralysis. MAIN OUTCOME MEASURES: Scandinavian Stroke Scale (SSS) and Barthel index (BI) on admission and weekly during rehabilitation. Univariate and multivariate statistics were considered. RESULTS: Of the 157 patients with initial leg paralysis, 84 (60%) died; 73 (40%) survived. Fifteen (21%) survivors regained walking function (the walking group), and 58 (79%) did not (the nonwalking group). The BI on admission was the only factor of significant predictive value (p < .03). Mean admission BI was 50 in the walking group versus 3 in the nonwalking group (p < .001). Age, gender, lesion size, total SSS score, and comorbidity had no predictive value. Within the first week, the walking group gained 3.2 points in the SSS subscore for leg strength versus 0.5 points in the nonwalking group (p < .02). CONCLUSION: Only 10% of stroke patients with initial leg paralysis regained independent walking. In these patients, BI on admission was high and leg strength improved quickly in the first week.