Leisure-time physical activity and ischemic stroke risk: the Northern Manhattan Stroke Study

In this study we have evaluated the postmortem pharmacokinetics of amitriptyline (Ami) and metabolites in pigs after oral and intravenous administration, and the results are compared with previous studies in rats and humans. In addition a meticulous investigation of blood and tissue concentrations after postmortem intravenous infusion of Ami was undertaken. Of a total of 9 over-night fasted pigs, 3 were given 25 mg/Kg Ami orally, and another 3 pigs received an intravenous infusion lasting 1 h of 3.3 mg/Kg Ami prior to death. The final 3 pigs were sacrificed and then given the intravenous infusion after death. After approximately 5 h at room temperature, all carcasses were subsequently stored at 4-5 degrees C. Postmortem blood samples were collected at 0.25, 1, 2, 4, 8, 24, 48, and 96 h through an indwelling intracardial needle. Postmortem examination with blood and tissue sampling was performed 96 h after death. Analysis was carried out by high performance liquid chromatography with ultraviolet detection. Postmortem blood samples from the heart of the orally dosed animals revealed large and variable concentration increases of 99(30-243)% for Ami and 96(52-429)% for the main metabolite 10-OH-Ami at 96 h. In the intravenously infused live pigs heart blood Ami increased by 55(33-69)% and 10-OH-Ami increased by 232(76-240)%. Blood from the atria had significantly higher Ami concentrations than blood from both ventricles in the animals dosed while alive, and the drug concentration in femoral blood was higher than in heart blood (p < 0.01). In the orally dosed pigs the left lobe of the liver had significantly higher Ami levels than the right lobe. Tissue/blood Ami concentration ratios were generally lower than previously reported in rats and approximating the levels reported in humans. The animals infused intravenously after death demonstrated high drug levels in blood samples from central vessels, heart, lungs as well as cerebrospinal fluid and vitreous humour. This implies that the presence of a lethal concentration of a drug in just one sample of heart blood can prove worthless in a case where agonal drug infusion may have occurred.     

Cost-effectiveness of tissue plasminogen activator for acute ischemic stroke. NINDS rt-PA Stroke Study Group

Tissue plasminogen activator (tPA) has been shown to improve 3-month outcome in stroke patients treated within 3 hours of symptom onset. The costs associated with this new treatment will be a factor in determining the extent of its utilization. Data from the NINDS rt-PA Stroke Trial and the medical literature were used to estimate the health and economic outcomes associated with using tPA in acute stroke patients. A Markov model was developed to estimate the costs per 1,000 patients eligible for treatment with tPA compared with the costs per 1,000 untreated patients. One-way and multiway sensitivity analyses (using Monte Carlo simulation) were performed to estimate the overall uncertainty of the model results. In the NINDS rt-PA Stroke Trial, the average length of stay was significantly shorter in tPA-treated patients than in placebo-treated patients (10.9 versus 12.4 days; p = 0.02) and more tPA patients were discharged to home than to inpatient rehabilitation or a nursing home (48% versus 36%; p = 0.002). The Markov model estimated an increase in hospitalization costs of $1.7 million and a decrease in rehabilitation costs of $1.4 million and nursing home cost of $4.8 million per 1,000 eligible treated patients for a health care system that includes acute through long-term care facilities. Multiway sensitivity analysis revealed a greater than 90% probability of cost savings. The estimated impact on long-term health outcomes was 564 (3 to 850) quality-adjusted life-years saved over 30 years of the model per 1,000 patients. Treating acute ischemic stroke patients with tPA within 3 hours of symptom onset improves functional outcome at 3 months and is likely to result in a net cost savings to the health care system.     

Lubeluzole treatment of acute ischemic stroke. The US and Canadian Lubeluzole Ischemic Stroke Study Group

BACKGROUND AND PURPOSE: Lubeluzole is a novel benzothiazole compound that has shown neuroprotective activity in preclinical models of ischemic stroke. The present multicenter, double-blind, placebo-controlled study was conducted to assess the efficacy and safety of lubeluzole in the treatment of ischemic stroke. METHODS: Seven hundred twenty-one patients with clinical symptoms of acute ischemic stroke were randomized to receive either lubeluzole (7.5 mg over 1 hour, followed by a continuous daily infusion of 10 mg for up to 5 days) or placebo. Treatment was initiated within 6 hours of symptom onset. Mortality at 12 weeks was the primary efficacy end point. Secondary efficacy end points included neurological recovery (based on the National Institutes of Health Stroke Scale [NIHSS]), functional status (based on the Barthel Index), and level of disability (based on the Rankin Scale). Safety assessments included standard and continuous electrocardiographic monitoring, physical examination, measurements of vital signs, clinical laboratory evaluation, and adverse events reports. RESULTS: The overall mortality rate at 12 weeks for lubeluzole-treated patients was 20.7% compared to 25.2% for placebo-treated patients (NS). Controlling for relevant covariates, the degree of neurological recovery (NIHSS) at week 12 significantly favored lubeluzole over placebo (P = .033). Lubeluzole treatment similarly resulted in significantly greater improvements in functional status (Barthel Index) (P = .038) and overall disability (Rankin Scale) (P = .034) after 12 weeks. A global test statistic confirmed that lubeluzole-treated patients had a more favorable clinical outcome at 12 weeks (P = .041). The safety profile of lubeluzole resembled that of placebo. CONCLUSIONS: Treatment with lubeluzole within 6 hours of the onset of ischemic stroke had a nonsignificant effect on mortality and resulted in improved clinical outcome compared with placebo, with no safety concerns.     

Using the NIH Stroke Scale to assess stroke patients. The NINDS rt-PA Stroke Study Group

The stroke patient is acutely ill within minutes of symptom onset. Typically, he or she is awake and thus requires a focal neurologic exam to evaluate vision, movement, sensation and language. With the advent of acute stroke treatments that need to be rapidly implemented, it is critical that the nurse be able to assess patients and relay the information accurately and efficiently to other members of the health care team. Performing and documenting the awake stroke exam in the most efficient and useful manner is key to the nursing care of the stroke patient. The National Institutes of Health Stroke Scale (NIHSS) is a systematic assessment tool designed to measure the neurologic deficits most often seen with acute stroke patients. Originally designed as a research tool, it is a nonlinear ordinal scale, with possible scores ranging form 0-42. Exam performance has been timed to take 5-8 minutes. Use of the NIHSS includes documentation of neurologic status and outcome, data collection for planning safe nursing care and standardization of information exchanges between nurse caregivers and other health care professionals.     

Mitral valve strands and the risk of ischemic stroke in elderly patients. The French Study of Aortic Plaques in Stroke (FAPS) Investigators

BACKGROUND AND PURPOSE: Strands are thin and filamentous attachments on the cardiac valves shown by transesophageal echocardiography. Their nature and their potential for embolization are largely unknown. The objective was to estimate the risk of brain infarction in patients with mitral valve strands. METHODS: Using transesophageal echocardiography, we compared the frequency of strands on native mitral valves in 284 consecutive patients admitted with brain infarction and 276 control patients, all older than 60 years. In a second part, case subjects were followed up over a 2- to 4-year period, and the risk of recurrence of brain infarction was estimated in patients with and without strands. RESULTS: In the case-control study, mitral valve strands were found in 22.5% of the case patients and in 12.1% of the control subjects. In case subjects, mitral valve strands were more frequent in those with mitral valve dystrophy (52.4% versus 37.4%; P = .03). Strands were not associated with mitral valve prolapse, annular calcifications, or left atrial spontaneous echocardiographic contrast. After adjustment for age, sex, and mitral valve dystrophy, the odds ratio for ischemic stroke among patients with mitral strands was 2.2 (95% confidence interval, 1.4 to 3.6; P = .005). The frequency of strands was not different in patients with a known cause of brain infarction (24.4%) from that in patients with no other apparent cause (20.9%). During 646 per 100 person-years of follow-up, the incidence of recurrent brain infarction was 6.0 person-years in patients with strands and 4.2 in those without. In the Cox analysis, including potential confounders and poststroke treatment, mitral valve strands did not appear as independent predictors of recurrent brain infarction (relative risk, 1.3; 95% confidence interval, 0.5 to 3.0; P = .54). CONCLUSIONS: The present study shows an independent association between mitral valve strands and the risk of brain infarction. However, the lack of an increased relative risk of recurrence raises doubts about the potential causal relation with brain infarction in patients aged 60 years or older.     

Risk factors for ischemic stroke: Dubbo Study of the elderly

Extensive clinical experience with the implantable cardioverter defibrillator (ICD) combined with recently completed prospective, randomized trials like MADIT and AVID, have demonstrated the lifesaving efficacy of this therapy and its superiority compared to conventional medical management in treating patients at high risk of sudden arrhythmic death. This evidence has in turn spurred great interest in further ICD studies. Since the ability of the ICD to save lives is no longer in question, there is a need to reexamine the real objectives of these new studies.     

The geographic variation in stroke incidence in two areas of the southeastern stroke belt: the Anderson and Pee Dee Stroke Study

BACKGROUND and PURPOSE: South Carolina and the southeastern United States have maintained the highest stroke mortality in the country. The Anderson and Pee Dee Stroke Study is an assessment of cerebrovascular disease incidence in 2 geographically defined communities in the stroke belt. METHODS: Strokes were identified in the Anderson and Pee Dee areas of South Carolina. All hospitalized and out-of-hospital deaths occurring during 1990 among the residents of these 2 areas were included. Strokes were classified by an independent panel of neurologists using a standard protocol that included specific criteria for stroke and subtypes. RESULTS: The overall age-adjusted stroke incidence rates (per 100 000 population) were significantly higher in the Pee Dee population (293.1) compared with Anderson (211.2). The geographic differences were more dramatic in the younger age groups of 35 to 64 years. Likewise, incidence rates for blacks were nearly twice the rates for whites. The rates in the Pee Dee were higher than the rates from other studies in the United States and other parts of the world. Although the stroke subtypes did not vary between the 2 regions, race-sex differences were identified. CONCLUSIONS: High stroke incidence and disease rates persist for all 4 race-sex groups in the Southeast and reflect similar risks as mortality rates. However, geographic variability in stroke rates suggests that the pattern of disease in the region is not so much a "belt" of increased stroke in contiguous areas but rather more a "necklace" of different levels of risk. These results should be useful in the identification of factors associated with this geographic enigma.     

Stroke 2: expanding the nurse's role in stroke rehabilitation

This article, the second of two considering the nurse's role in stroke rehabilitation, focuses on potential nursing contributions in a number of areas. There is scope, particularly in the community, to develop a far greater nursing role in both the acute and the postacute phases of rehabilitation. However, nurses often have ambivalent attitudes towards rehabilitation--seeing acute care as more prestigious and important. Such attitudes are developed and reinforced in basic training which gives relatively little emphasis to chronic illness.     

Role thrombocytes in etiopathogenesis of ischemic stroke

This paper presents the most essential problems concerning the role of platelets in the genesis of ischaemic brain disease and their role in spreading of ischaemic focus. The role of platelets in atherogenesis and development of vascular abnormalities in arterial hypertension and diabetes mellitus was considered, and attention was paid to conditions concerned with the pathogenesis of ischaemic stroke such as presence of antiphospholipid antibodies and presence of large volume platelets, in which platelet activation plays essential role. Then it was shown that platelet hyperactivation occurs in acute phase of ischaemic stroke and mechanisms of destructive action of activated platelets on recent ischaemic focus in brain such as secretion of neurotoxins and blocking of microcirculation by platelet aggregates were discussed.     

Local intra-arterial thrombolysis in acute ischemic stroke

BACKGROUND AND PURPOSE: We performed a retrospective analysis of the prognostic factors in patients treated with local intra-arterial thrombolysis (LIT). The purpose of this study was to evaluate the safety and efficacy of LIT using urokinase in patients with acute ischemic stroke of the anterior or posterior circulation and to determine the influence of clinical and radiological parameters on outcome. METHODS: Forty-three patients were treated with LIT using urokinase (median dose, 0.75x10(6) IU). The median National Institutes of Health Stroke Scale (NIHSS) score at hospital admission was 18 (range, 9 to 36). Nine patients had occlusions of the internal carotid artery (ICA), 23 of the middle cerebral artery (MCA), 1 of the anterior cerebral artery, and 10 of the basilar artery (BA). Outcome was assessed after 3 months and classified as good for Rankin Scale (RS) scores of 0 to 3 and poor for RS scores of 4 or 5 and death. RESULTS: Nine patients (21%) recovered to RS scores 0 or 1, 17 (40%) to scores of 2 or 3, and 7 (16%) to scores of 4 or 5. Ten patients (23%) died. Outcome was good in 17 patients (80%) with MCA occlusions, in 3 patients (33%) with ICA, and in 5 patients (50%) with BA occlusions. Good outcome was associated with an initial NIHSS score of <20 (P<0.001), improvement by 4 or more points on NIHSS score within 24 hours (P=0.001), and vessel recanalization (P=0.02). Recanalization was more likely if LIT was started within 4 hours (P=0.01). Symptomatic cerebral hemorrhage occurred in 2 patients (4.7%). CONCLUSIONS: LIT was most efficacious in patients with MCA and BA occlusions when the initial NIHSS score was less than 20 and when treated within 4 hours. It is of limited value in patients with distal ICA occlusions.     

Observations on isovolemic hemodilution in acute ischemic stroke

The reduction of blood viscosity is an alternative of the improvement of the cerebral flow during an acute ischemic stroke (AIS). We studied 18 patients with AIS, ranging in age from 44 to 72 years (mean age 57 years), 11 females and 7 males. We applied an isovolemic hemodilution for 2 days starting with an emission of 250 or 500 ml blood, followed by the infusion of an equal amount of 6% HAES-steryl solution. We made determination of hematocrit, plasma density, plasma viscosity 1, 3 and 6 hours before and after the infusion; a decrease was noted in all the studied hemorheologic parameters, and the short term clinical course was an improvement. In conclusion, the isovolemic hemodilution using 6% HAES solution reduced hematocrit, plasma density, plasma viscosity but no changes were noted in the hemodynamic parameters; isovolemic hemodilution as the single therapeutic method in AIS does not solve the therapy, involving only one pathogenetic link, i.e., the microcirculation.     

Asymptomatic cerebral infarctions in patients with ischemic stroke

We studied 383 consecutive patients with stroke and ischemic lesions on CT scan for the presence of symptomatic cerebral infarction (SCI) and asymptomatic cerebral infarction (ACI). We evaluated risk factors as well as volume, site and number of the lesions. ACIs occurred in 34% of the cases (130/383); 88% of ACIs were lacunes and internal borderzone infarctions, with a volume of less than 2 ml. Larger infarctions were asymptomatic in 27 patients (20.8%); 114 (68.7%) out of 166 patients with two or more SCIs (68.7%) had one or more ACIs. Infarctions in the lateral middle cerebral artery (MCA) territory were SCIs, in the medial MCA territory ACIs. Independent risk factors for ACI were age above 70 years and smoking; cardioembolism prevailed in SCI, small vessel disease in ACI; high levels of disability prevailed in SCIs.