National registry-based case-control study: comorbidity and stroke in young adults.

OBJECTIVES: Stroke is overrepresented in cohorts of young adults with chronic diseases. The prevalence and impact of comorbidity among young stroke patients have not been compared with individuals without stroke. Our aim was to investigate the association between comorbidity and stroke in young adults. MATERIALS AND METHODS: A nationwide cohort of patients (aged 15-44 years), registered in the Swedish Stroke Register, (Riksstroke) 2001-2009, was identified. Age- and sex-matched controls were randomly selected from the Population Register of Sweden. Discharge diagnoses were retrieved from the National Patient Register and grouped by chapter in the International Classification of Diseases 10th revision. Associations between ICD-10 chapters and stroke were stratified (age, sex, and stroke type) and analyzed by multivariable logistic regression. RESULTS: In 2599 stroke patients analyzed, the prevalence of vascular risk factors (hypertension 25.3%, dyslipidemia 13.0%, diabetes 9.7%, heart failure 3.2%, and atrial fibrillation 2.8%), all ICD-10 chapters (except pregnancy) and prestroke hospitalizations were more frequent among cases than controls. Independent associations were found between stroke and eight ICD-10 chapters: neoplasms (odds ratios (OR) 1.53, 95% CI 1.15-2.05), blood (OR 1.61, 1.11-2.34), endocrine (OR 2.28, 1.77-2.93), psychiatric (OR 1.50, 1.24-1.81), nervous (OR 1.91, 1.46-2.50), eye (OR 1.67, 1.05-2.64), circulatory (OR 3.05, 2.45-3.80), and symptoms (OR 1.31, 1.13-1.52). The risk of stroke increased by 26% per ICD-10 chapter diagnosed. CONCLUSIONS: In addition to vascular risk factors, comorbidity (represented by ICD-10 chapters) was associated with increased risk of stroke in young individuals. The risk of stroke was further increased with the number of diagnosed ICD-10 chapters.

The prevalence of atrial fibrillation in a geographically well-defined population in northern Sweden: implications for anticoagulation prophylaxis.

OBJECTIVES: The aims of this study were to evaluate the community-based prevalence of atrial fibrillation (AF) in a western society using a geographically well-defined population in the northern part of Sweden as a reference and to estimate the proportion of patients eligible for oral anticoagulation (OAC) prophylactic therapy according to the stroke risk indices CHADS2 and CHA2 DS2 -VASc. Bleeding risk was assessed using the HAS-BLED score. DESIGN: The study population was recruited from AURICULA, a Swedish national quality register for patients receiving anticoagulation treatment. All patients with the diagnosis AF in the catchment area are registered in AURICULA. RESULTS: Of the 65 532 inhabitants in the catchment area, 1616 were diagnosed with AF (1200 cases were characterized as chronic AF). Thus, the overall prevalence of AF was 2.5%. The prevalence increased with age from 6.3% in patients over 55 years of age to 13.8% in those over 80 years. The prevalence was higher in men than in women in all age groups. Overall, 56.3% and 85.1% of the population were at high risk of stroke (≥2 points) according to CHADS2 and CHA2 DS2 -VASc, respectively. In addition, 26.9% had an increased bleeding risk according to HAS-BLED. CONCLUSION: Within this large Caucasian population, we identified the highest community-based prevalence of AF to date. The prevalence was strongly associated with increasing age and male gender. Using CHA2 DS2 -VASc instead of CHADS(2) widened the indication for OAC prophylactic therapy of AF in this population.

Validation of the Swedish inpatient and cause-of-death registers in the context of stroke.

BACKGROUND: Quality follow-up within stroke care is important in times when stroke prevalence is increasing and health care funds are limited. Administrative data, such as data from the inpatient register (IPR) and the cause-of-death register (CDR) are often used for this purpose, but the validity of such data has not been ascertained. METHODS: During the year 1999-2000, a community-based stroke register was established in a Swedish municipality. Data from that register was compared with two administrative registers, the IPR and the CDR. RESULTS: Using multiple overlapping data sources, 377 patients with first-ever stroke were found in the community-based register. Forty-four of these (12%) were missing in the IPR/CDR. Non-hospitalized patients were less likely to be registered in the IPR/CDR, as were patients who were not initially treated in a stroke unit. Stroke severity was lower among non-registered patients. Thirty patients (8%) in the IPR/CDR were misclassified as stroke patients. CONCLUSIONS: Quality follow-up within stroke care could be biased or have low comparability, when administrative data are used. Great caution should be taken when data are derived from the inpatient and cause-of-death registers, and more validation work needs to be carried out in the context of stroke.

Ten-year risk for myocardial infarction in patients with first-ever stroke: a community-based study.

BACKGROUND: Stroke and coronary heart disease (CHD) share common risk factors. The risk for stroke patients to have a myocardial infarction (MI) has not been fully explored. METHODS: Three hundred and seventy-seven first-ever stroke patients were ascertained prospectively. The 10-year incidence of MI was examined by register searches. The results were compared to the general Swedish population. Predictors for MI were identified using univariate and multivariate analysis. RESULTS: The cumulative incidence of MI over 10 years was 25.0/100 (95% confidence interval (CI), 19.5-31.5), 26.5 for men, (95% CI, 18.9-45.8) and 23.4 for women (95% CI, 16.0-32.9). Compared to the general population, the relative risk for stroke patients having a MI was 1.6 for men (95% CI, 1.12-2.37) and 1.9 for women (95% CI, 1.27-2.90). In multivariate analysis, CHD before the stroke (MI, angina pectoris, coronary artery bypass grafting, or percutaneous transluminal coronary angioplasty) and peripheral artery disease were significant predictors for MI. CONCLUSION: The risk for MI is significantly higher, for both male and female stroke patients, compared to the general population. Stroke patients with previous CHD and peripheral artery disease are at highest risk. Stroke patients should receive adequate secondary prevention, and cardiac complaints must be taken seriously.

Comparison of 90-day case-fatality after ischemic stroke between two different stroke outcome registries using propensity score matching analysis.

BACKGROUND: It has not been clarified whether the disparity in ischemic stroke outcome between populations is caused by ethnic and geographic differences or by variations in case mix. Propensity score matching (PSM) analysis can overcome some analytical problems but is rarely used in stroke outcome research. This study was to compare the ischemic stroke case-fatality between two PSM cohorts of Sweden and Korea. METHODS: Prognostic variables related to baseline characteristics and stroke care were included in our PSM model. Then, we selected 7675 Swedish and 1220 Korean patients with ischemic stroke from each stroke registers and performed one-to-one matching based on propensity scores of each patient. RESULTS: After PSM, all measured variables were well balanced in 1163 matched subjects, and the 90-day case-fatality was identical 6.2% (HR 0.997, 95%CI 0.905-1.099) in Sweden and Korea. CONCLUSIONS: No difference is found in the 90-day case-fatality in propensity score-matched Swedish and Korean patients with ischemic stroke.

The molecular basis of thrombolysis and its clinical application in stroke.

The rationale for thrombolysis, the most promising pharmacological approach in acute ischaemic stroke, is centred on the principal cause of most ischaemic strokes: the thrombus that occludes the cerebral artery, and renders part of the brain ischaemic. The occluding thrombus is bound together within fibrin. Fibrinolysis acts by activation of plasminogen to plasmin; plasmin splits fibrinogen and fibrin and lyses the clot, which then allows reperfusion of the ischaemic brain. Thrombolytic agents include streptokinase (SK) and recombinant tissue-type plasminogen activator (rt-PA) amongst others under test or development. SK is nonfibrin-specific, has a longer half-life than tissue-type plasminogen activator (t-PA), prevents re-occlusion and is degraded enzymatically in the circulation. rt-PA is more fibrin-specific and clot-dissolving, and is metabolized during the first passage in the liver. In animal models of ischaemic stroke, the effects of rt-PA are remarkably consistent with the effects seen in human clinical trials. For clinical application, some outcome data from the Cochrane Database of Systematic Reviews which includes all randomized evidence available on thrombolysis in man were used. Trials included tested urokinase, SK, rt-PA, pro-urokinase, or desmoteplase. The chief immediate hazard of thrombolytic therapy is fatal intracranial bleeding. However, despite the risk, the human trial data suggest the immediate hazards and the apparent substantial scope for net benefit of thrombolytic therapy given up to 6 h of acute ischaemic stroke. So far the fibrin-specific rt-PA is the only agent to be approved for use in stroke. This may be due to its short half-life and its absence of any specific amount of circulating fibrinogen degradation products, thereby leaving platelet function intact. The short half-life does not leave rt-PA without danger for haemorrhage after the infusion. Due to its fibrin-specificity, it can persist within a fibrin-rich clot for one or more days. The molecular mechanisms with regards to fibrin-specificity in thrombolytic agents should, if further studied, be addressed in within-trial comparisons. rt-PA has antigenic properties and although their long-term clinical relevance is unclear there should be surveillance for allergic reactions in relation to treatment. Although rt-PA is approved for use in selected patients, there is scope for benefit in a much wider variety of patients. A number of trials are underway to assess which additional patients - beyond the age and time limits of the current approval - might benefit, and how best to identify them.

A review on sex differences in stroke treatment and outcome.

BACKGROUND: Beyond epidemiological differences, it has been controversial whether any important sex differences exist in the treatment of stroke. In this review paper, the following areas are covered: thrombolysis, stroke unit care, secondary prevention, surgical treatment, and rehabilitation. Additionally, symptoms at stroke onset, as well as outcome measures, such as death, dependency, stroke recurrence, quality of life, and depression are reviewed. METHODS: Search in PubMed, tables-of-contents, review articles, and reference lists after studies that include information about sex differences in stroke care. RESULTS: Ninety papers are included in this review. Women suffer more from cortical and non-traditional symptoms. Men and women benefit equally from thrombolysis and stroke unit care. Women with cardioembolic strokes may benefit more from anticoagulant therapy. Most studies have not found any tendency towards sexism in the choice of treatment. Post-stroke depression and low quality-of-life seem to be more common among women. Mortality rates are higher among men in some studies, while long-term ADL-dependency seems to be more common among women. CONCLUSIONS: Sex differences in stroke treatment and outcome are small, with no unequivocal proof of sex discrimination. Women have less favourable functional outcome because of higher age at stroke onset and more severe strokes.

Radiation to supraclavicular and internal mammary lymph nodes in breast cancer increases the risk of stroke.

The aim of this study was to assess whether adjuvant treatment of breast cancer (BC) affects the risk of stroke, and to explore radiation targets and fraction doses regarding risk and location of stroke. In a Swedish BC cohort diagnosed during 1970-2003, we carried out a nested case-control study of stroke after BC, with relevant details extracted from medical records. The odds ratio (OR) for radiotherapy (RT) vs that of no RT did not differ between cases and controls (OR=0.85; confidence interval, CI=0.6-1.3). Radiotherapy to internal mammary chain (IMC) and supraclavicular (SCL) lymph nodes vs that of no RT was associated with a higher, although not statistically significant, risk of stroke (OR=1.3; CI=0.8-2.2). In a pooled analysis, RT to IMC and SCL vs the pooled group of no RT and RT to breast/chest wall/axilla (but not IMC and SCL), showed a significant increase of stroke (OR=1.8; CI=1.1-2.8). There were no associations between cancer laterality, targets of RT, and location of stroke. The radiation targets, IMC and SCL, showed a statistically significant trend for an increased risk of stroke with daily fraction dose. Our finding of a target-specific increased risk of stroke and a dose-response relationship for daily fraction dose, indicate that there may be a causal link between RT to the IMC and SCL and risk of stroke.

Stroke unit care revisited: who benefits the most? A cohort study of 105,043 patients in Riks-Stroke, the Swedish Stroke Register.

BACKGROUND: Treatment at stroke units is superior to treatment at other types of wards. The objective of the present study is to determine the effect size of stroke unit care in subgroups of patients with stroke. This information might be useful in a formal priority setting. METHODS: All acute strokes reported to the Swedish Stroke Register from 2001 through 2005 were followed until January 2007. The subgroups were age (18-64, 65-74, 75-84, 85+ years and above), sex (male, female), stroke subtype (intracerebral haemorrhage, cerebral infarction and unspecified stroke) and level of consciousness (conscious, reduced, unconscious). Cox proportional hazards and logistic regression analyses were used to estimate the risk for death, institutional living or dependency. RESULTS: 105,043 patients were registered at 86 hospitals. 79,689 patients (76%) were treated in stroke units and 25,354 patients (24%) in other types of wards. Stroke unit care was associated with better long-term survival in all subgroups. The best relative effect was seen among the following subgroups: age 18-64 years (hazard ratio (HR) for death 0.53; 0.49 to 0.58), intracerebral haemorrhage (HR 0.61; 0.58 to 0.65) and unconsciousness (HR 0.70; 0.66 to 0.75). Stroke unit care was also associated with reduced risk for death or institutional living after 3 months. CONCLUSIONS: Stroke unit care was associated with better long-term survival in all subgroups, but younger patients, patients with intracerebral haemorrhage and patients who were unconscious had the best relative effect and may be given the highest priority to this form of care.

Risk factors for stroke-related pain 1 year after first-ever stroke.

OBJECTIVE: To estimate the prevalence of stroke-related pain and to explore its relation to spasticity. DESIGN: Cross-sectional survey. PATIENTS AND METHODS: One hundred and forty patients were examined at 1 year after first-ever stroke. Pain was assessed by a structured interview and categorized as stroke-related or not, pain intensity by use of the visual analogue scale (VAS), spasticity by use of the modified Ashworth scale, stroke severity and the presence of specific neurological impairments by use of the National Institute of Health Stroke Scale (NIHSS), and depression by use of the Montgomery-Asberg Depression Scale. RESULTS: Pain was reported by 68 patients (49%) with a mean VAS of 42 (95% CI 36-47). In 29 patients (21%), pain was categorized as stroke-related pain. Univariate analyses demonstrated correlations between stroke-related pain and total NIHSS score, paresis, sensory disturbance, depression and spasticity respectively. A multiple regression analysis demonstrated an independent association of stroke-related pain with paresis (OR = 3.1, 95% CI 1.2-7.7), sensory disturbance (OR = 3.1, 95% CI 1.1-8.9) and depression (OR = 4.1, 95% CI 1.4-13). CONCLUSIONS: The estimated prevalence of stroke-related pain was 21%. Stroke-related pain was associated with sensorimotor impairments and depression, but not with spasticity as an independent variable.

MEK-inhibitor U0126 in hyperglycaemic focal ischaemic brain injury in the rat.

BACKGROUND: Hyperglycaemia aggravates ischaemic brain injury, possibly due to activation of signalling pathways involving mitogen-activated protein kinases (MAPK). In this study, the activation of MAPK/ERK was inhibited using the upstream inhibitor of MAPK-ERK-kinase (MEK) U0126, and the effects on focal brain ischaemia were evaluated during normo- and hyperglycaemia. MATERIALS AND METHODS: Temporary (90 min) middle cerebral artery occlusion (MCAO) was induced in five groups of rats. U0126 (400 microg kg(-1)) or vehicle was given as 60-min intravenous infusions starting either 30 min prior to MCAO or 30 min prior to reperfusion. The infarct size was determined by perfusion with tetrazolium red after 24 h of survival, and the neurology was tested with the 4-level scale of Bederson and performance on an inclined plane. The inhibitory effect on the targeted MEK enzyme was investigated by analysing the phosphorylation of the downstream target ERK with western immunoblotting. Two subgroups were investigated with magnetic resonance imaging (MRI), including diffusion-weighted (DWI) and perfusion-weighted imaging (PWI). RESULTS: U0126 effectively reduced the infarct size and improved neurology in hyperglycaemic rats both when given before and after ischemic onset. This effect was not accompanied by any detectable changes in cerebral blood flow on MRI. Normoglycaemic rats had generally milder injuries compared with the hyperglycaemic and there was a nonsignificant trend for U0126 to reduce damage also in the nonhyperglycaemic groups. CONCLUSIONS: In conclusion, U0126 appears to be neuroprotective in this model of hyperglycaemic ischaemic brain injury. The findings support the pathogenic importance of the MEK-ERK pathway in hyperglycaemic-ischaemic brain injury.

Prevalence of disabling spasticity 1 year after first-ever stroke.

OBJECTIVE: To estimate the prevalence of disabling spasticity (DS) 1 year after first-ever stroke. DESIGN: Cross-sectional survey 1 year after first-ever stroke. METHODS: Patients above 18 years from one county with first-ever stroke were identified by use of the national stroke registry. A representative sample of 163 patients was created and 140 of these were followed up. Assessments of motor function and ability with the modified Ashworth Scale, the modified Rankin Scale (mRS), the Barthel Index (BI) and clinical evaluation were performed in order to identify patients with spasticity-related disability. RESULTS: The observed prevalence of any spasticity was 17% and of DS 4%. Patients with DS scored significantly worse than those with no DS on the mRS (P = 0.009) and the BI (P = 0.005). DS was more frequent in the upper extremity, correlated positively with other indices of motor impairment and inversely with age. There was an independent effect of severe upper extremity paresis (OR 22, CI 3.9-125) and age below 65 years (OR 9.5, CI 1.5-60). CONCLUSIONS: The prevalence of DS after first-ever stroke is low but corresponds to a large number of patients and deserves further attention with regards to prevention and treatment.

A national stroke quality register: 12 years experience from a participating hospital.

Registration of all hospitalized stroke patients is practiced in Sweden in order to assess care quality. Data in this register, Riks-Stroke (RS), may be biased due to incomplete registration. The purpose of this paper was to report changes in stroke outcome in relation to fluctuations in registration. Patients registered in RS at a hospital during the period 1994-2005 were analyzed. Case fatality at 28 days, living conditions, and activities of daily living (ADL) performance at 3 months were correlated to the number of patients registered and follow-up frequency. A total of 4994 stroke cases were registered during the period. A high annual registration rate was significantly correlated to a high case fatality ratio. A low annual follow-up rate was associated with a low proportion of patients living in their own home without any need of help. Quality parameters are sensible for selection bias, which make them difficult to compare over time and between hospitals. We suggest that by weighing outcome data against stroke severity, safer conclusions may be drawn. Additionally, hospitals considering setting up quality registers should make every effort to attain complete case ascertainment at all times, including patients managed outside the hospital, in order to avoid selection bias.

Cerebrospinal fluid markers of disturbed brain cell metabolism.

Reversibly and irreversibly disturbed brain cell metabolism may be monitored in an indirect way by the analyses of enzymes in the CSF according to the hypothesis of cell swelling induced by energy shortage. Adenylate kinase fulfils the criteria for an ideal CSF marker with the exception that it is not organspecific, which necessitates precautions to avoid influence of AK in erythrocytes and serum. When taking such limitating factors into account, AK determinations may be diagnostically useful in combination with radiological and clinical observations. Besides, it is possible that a combination of AK analyses and clinical signs are useful in the prognostication in individual patients suffering from global cerebral ischemia and cerebral infarction.

Hormone replacement therapy and the risk of stroke. Follow-up of a population-based cohort in Sweden.

BACKGROUND: The protective effect of postmenopausal estrogen replacement therapy on coronary heart disease has been shown in several studies. However, the effect on stroke is more controversial, and data on estrogen-progestin combinations are sparse. METHODS: A total of 23,088 women living in the Uppsala (Sweden) Health Care Region were identified from pharmacy records as having been prescribed noncontraceptive estrogens during 1977 through 1980. They were followed up from 1977 to 1983 for admissions to the hospital because of a first stroke (International Classification of Diseases, Eighth Revision, codes 430 through 438 and 344). The mean observation time was 5.8 years. The expected number was based on person-years in the cohort and incidence rates in the population of the region. RESULTS: Overall, 361 cases of first stroke were observed in the cohort, as compared with 403.2 expected (relative risk [RR], 0.90; 95% confidence limits, 0.81, 0.99). The RR for acute stroke (International Classification of Diseases, Eighth Revision, codes 431 through 436) was 0.85 (0.75, 0.97). In women younger than 60 years at entry who were prescribed estradiol compounds (1 to 2 mg) or conjugated equine estrogens (0.625 to 1.25 mg), the risk of any stroke was reduced by almost 30% (RR, 0.72; 0.58, 0.88) and the risk of acute stroke was reduced by 40% (RR, 0.61; 0.46, 0.79). Women prescribed a combined estradiol-levonorgestrel brand also had a lowered risk of stroke (RR, 0.61; 0.40, 0.88). Weak compounds (mainly estriol) showed no stroke-protective effect, nor was there any relationship between hormone replacement and risk of subarachnoid hemorrhage. CONCLUSION: Hormone replacement therapy with potent estrogens alone or cyclically combined with progestins can, particularly when started shortly after menopause, reduce the risk of stroke.

Expression of vascular endothelial growth factor (VEGF) and its receptors (Flt-1 and Flk-1) following permanent and transient occlusion of the middle cerebral artery in the rat.

Vascular endothelial growth factor (VEGF) is a known endothelial mitogen and a potent enhancer of vascular permeability although its role in focal cerebral ischemia is still not completely understood. The present report describes the immunohistochemical distribution of VEGF and its 2 receptors, Flt-1 and Flk-1 at day 1 and 3 following permanent and transient middle cerebral artery occlusion (MCAO) in the rat. A bilateral increase in VEGF immunoreactivity, particularly in neurons and blood vessels, was seen in both the experimental designs by day 1. By day 3, the immunoreactivity was restricted chiefly to the lesion side, where reaction was most prominent in the border zones of the infarcts. Immunoreaction to VEGF was more pronounced in cases of permanent MCAO than in transient MCAO. Flt-1 reaction was increased in neurons, glial and endothelial cells after both transient and permanent MCAO. Immunoreactivity to Flk-1 was prominent in glial cells and was present to some extent in endothelial cells. These findings indicate an early upregulation of VEGF and its receptors after permanent as well as transient focal cerebral ischemia in the rat.

Effects of a perindopril-based blood pressure-lowering regimen on disability and dependency in 6105 patients with cerebrovascular disease: a randomized controlled trial.

BACKGROUND AND PURPOSE: We sought to quantify the effects of blood pressure lowering on long-term disability and dependency among patients with cerebrovascular disease. METHODS: We performed a randomized, double-blind, placebo-controlled trial. A total of 6105 participants with a history of stroke or transient ischemic attack in the past 5 years were recruited from 172 hospital outpatient clinics in 10 countries. Subjects were randomly assigned to the following groups: active treatment (angiotensin-converting enzyme inhibitor perindopril [4 mg/d] for all patients, with the diuretic indapamide added at the discretion of treating physicians) or matching placebo(s). Measurements were disability (defined as a Barthel Index score < or =99/100) and dependency (a positive response to the following question: "In the last 2 weeks has the patient required regular help with everyday activities?"). RESULTS: The median duration of follow-up was 4 years. At the last available assessment, 19% of the active treatment group and 22% of the placebo group were disabled (adjusted odds ratio, 0.76; 95% CI, 0.65 to 0.89; P<0.001). Twelve percent of the active treatment group and 14% of the placebo group were dependent (adjusted odds ratio, 0.84; 95% CI, 0.71 to 0.99; P=0.04). The effects of treatment appeared to be mediated primarily through the prevention of disability and dependency associated with recurrent stroke. Four-year treatment with the study drug regimen would be expected to result in the avoidance of 1 case of long-term disability for every 30 (95% CI, 19 to 79) patients. CONCLUSIONS: Among individuals with cerebrovascular disease, a perindopril-based blood pressure-lowering regimen not only reduced the risk of stroke and major vascular events but also substantially reduced the risks of associated long-term disability and dependency.

Acupuncture and transcutaneous nerve stimulation in stroke rehabilitation: a randomized, controlled trial.

BACKGROUND AND PURPOSE: In small trials with control groups that receive no intervention, acupuncture has been reported to improve functional outcome after stroke. We studied effects of acupuncture and transcutaneous electrical nerve stimulation on functional outcome and quality of life after stroke versus a control group that received subliminal electrostimulation. METHODS: In a multicenter randomized controlled trial involving 7 university and district hospitals in Sweden, 150 patients with moderate or severe functional impairment were included. At days 5 to 10 after acute stroke, patients were randomized to 1 of 3 intervention groups: (a) acupuncture, including electroacupuncture; (b) sensory stimulation with high-intensity, low-frequency transcutaneous electrical nerve stimulation that induces muscle contractions; and (c) low-intensity (subliminal) high-frequency electrostimulation (control group). A total of 20 treatment sessions were performed over a 10-week period. Outcome variables included motor function, activities of daily living function, walking ability, social activities, and life satisfaction at 3-month and 1-year follow-up. RESULTS: At baseline, patients in each group were closely similar in all important prognostic variables. At 3-month and 1-year follow-ups, no clinically important or statistically significant differences were observed between groups for any of the outcome variables. The 3 treatment modalities were all conducted without major adverse effects. CONCLUSIONS: When compared with a control group that received subliminal electrostimulation, treatment during the subacute phase of stroke with acupuncture or transcutaneous electrical nerve stimulation with muscle contractions had no beneficial effects on functional outcome or life satisfaction.

Age relations of cardiovascular risk factors in a traditional Melanesian society: the Kitava Study.

This study examined cross-sectional age relations of blood pressure, anthropometric indexes, serum lipids, and hemostatic variables in 203 subsistence horticulturists aged 20-86 y in Kitava, Trobriand Islands, Papua New Guinea. The population is characterized by extreme leanness (despite food abundance), low blood pressure, low plasma plasminogen activator inhibitor 1 activity, and rarity of cardiovascular disease. Tubers, fruit, fish, and coconut are dietary staples whereas dairy products, refined fat and sugar, cereals, and alcohol are absent and salt intake is low. Although diastolic blood pressure was not associated with age in Kitavans, systolic blood pressure increased linearly after 50 y of age in both sexes. Body mass index decreased with age in both sexes. Serum total cholesterol, triacylglycerol, low-density-lipoprotein cholesterol, and apolipoprotein B increased in males between 20 and 50 y of age, whereas high-density-lipoprotein cholesterol and apolipoprotein A-I decreased. There were no significant differences in these indexes with age in the few females studied. A slight linear age-related increase of lipoprotein(a) was present in males. Plasma fibrinogen, factor VII clotting activity, factor VIII clotting activity, and von Willebrand factor antigen increased with age in both sexes but plasminogen activator inhibitor 1 activity did not. The modest or absent relations between the indexes measured and age are apparently important explanations of the virtual nonexistence of stroke and ischemic heart disease in Kitava.

Eosinophil cationic protein (ECP) in the cerebrospinal fluid.

ECP (eosinophil cationic protein) has been measured by means of a specific radioimmunoassay in the cerebrospinal fluid (CSF) from 210 individuals with various diseases affecting the central nervous system. In the same specimens lactoferrin and albumin were measured as well, as indicators of neutrophil-involved inflammation and damage to the blood-brain barrier. From a patient reference group (n = 39) the upper "normal" limit for ECP was estimated to 1.7 microgram/l. In patients with acute cerebrovascular disease (n = 108) ECP levels were elevated in 38% of the cases which was a significantly (P less than 0.001) greater proportion than seen for lactoferrin (7%). In patients with acute infections of the CNS (n = 30) 67% had raised ECP levels with significantly higher levels (P less than 0.001) in those having bacterial infections. The ECP levels were significantly correlated (P less than 0.001) to the lactoferrin-levels in the whole infectious group. In patients with tumours (n = 25) raised levels of ECP were found in 67% of those with malignant and in 6% of those having benign tumours. This difference was statistically significant (P = 0.001). The ECP levels were closely related to those of lactoferrin (P less than 0.001) and albumin (P less than 0.005). Of the patients with multiple sclerosis (n = 19) 25% had raised ECP levels. This proportion was not significantly different from those having raised lactoferrin levels. In three patients extremely high ECP levels (70-455 micrograms/l) were found and a causal relationship between ECP and the brain tissue damage in these patients is suggested. In comparison with the neutrophil-related data the findings suggest a preferential involvement of eosinophils in some diseases affecting the central nervous system.