Biomedical subjects

David Tanne

Publications and source records attributed to David Tanne.

At least 19 recordsLinked to original sources

PubMed2006

Effects of peroxisome proliferator-activated receptor ligands, bezafibrate and fenofibrate, on adiponectin level.

OBJECTIVE: Adiponectin is adipose-specific secretory protein and acts as anti-diabetic and anti-atherosclerotic molecule. We previously found peroxisome proliferators response element in adiponectin promoter region, suggesting that peroxisome proliferator-activated receptor (PPAR) ligands elevate adiponectin. Fibrates are known to be PPARalpha ligands and were shown to reduce risks of diabetes and cardiovascular disease. Effect of fibrates on adiponectin has not been clarified, whereas thiazolidinediones enhance adiponectin. Thus, we explored the possibility and mechanism that fibrates enhance adiponectin in humans, mice, and cells. METHODS AND RESULTS: Significant increase of serum adiponectin was observed in bezafibrate-treated subjects compared with placebo group in patients enrolled in The Bezafibrate Infarction Prevention study. Higher baseline adiponectin levels were strongly associated with reduced risk of new diabetes. Fibrates, bezafibrate and fenofibrate, significantly elevated adiponectin levels in wild-type mice and 3T3-L1 adipocytes. Such an effect was not observed in PPARalpha-deficient mice and adipocytes. Fibrates activated adiponectin promoter but failed to enhance its activity when the point mutation occurred in peroxisome proliferators response element site and the endogenous PPARalpha was knocked down by PPARalpha-RNAi. CONCLUSIONS: Our results suggest that fibrates enhance adiponectin partly through adipose PPARalpha and measurement of adiponectin might be a useful tool for searching subjects at high risk for diabetes.

Adipocytes↗

PubMed2006

Calcification of the thoracic aorta by spiral computed tomography among hypertensive patients: associations and risk of ischemic cerebrovascular events.

BACKGROUND: Calcium is often deposited in the aorta, but the associations and clinical implications of calcification of the aorta have not yet been elucidated. METHODS: In a prospective cohort of 455 hypertensive patients with at least 1 additional risk factor for atherosclerosis that underwent dual slice spiral computed tomography of the chest for assessment of arterial calcification (mean age 65.7+/-5.8, range 52-80 years, 48% female), we assessed for calcifications of the ascending and descending aorta and their association with the risk of subsequent ischemic cerebrovascular events during 3-year follow-up. RESULTS: Calcification of the ascending or descending aorta was present in 342 (75%) patients (60% calcification of the ascending aorta and 56% of the descending aorta). The main associations of calcification of the thoracic aorta were increasing age and the presence of coronary calcification, mitral annulus calcification, and aortic valve calcification. In a logistic regression model the main predictors of ischemic cerebrovascular events (n=27) during follow-up were the presence of severe calcification (thickness of > or = 5 mm) of the descending aorta (OR 4.9, 95%CI 1.8 to 13.5) and cigarette smoking (OR 2.8, 95%CI 1.1 to 6.7). CONCLUSIONS: Calcification of the thoracic aorta is highly prevalent among women and men with hypertension, is age-related, and correlates with calcification of the coronary arteries and heart valves. Only severe calcification of the descending aorta is associated with subsequent ischemic cerebrovascular events, suggesting that calcification of the thoracic aorta is a marker of the burden of vascular disease.

Aged↗

PubMed2006

Long-term effect of bezafibrate on pancreatic beta-cell function and insulin resistance in patients with diabetes.

OBJECTIVE: Development of insulin resistance (IR) and the progressive failure of the pancreatic beta-cell function (BCF) may be important in the pathogenesis of type 2 diabetes. Influence of peroxisome proliferator-activated receptors ligand bezafibrate on BCF and IR in patients with diabetes is unknown. The present study was aimed to investigate the long-term effect of bezafibrate on these parameters in diabetic patients enrolled in the Bezafibrate Infarction Prevention (BIP) Study. METHODS: Metabolic and inflammatory parameters were analyzed from stored frozen plasma samples obtained from 351 diabetic patients (168 treated by bezafibrate and 183 by placebo) who completed a 2-year of randomized, double-blind, placebo-controlled study period. The homeostatic indexes of BCF (HOMA-BCF) and IR (HOMA-IR) were calculated according to the homeostasis model of assessment. RESULTS: Both groups displayed similar baseline characteristics. During follow-up, in the placebo group there was 28% rise of HOMA-IR (p<0.001). In contrast, HOMA-IR in patients in the bezafibrate group did not change (p=0.99). The intergroup differences in HOMA-IR percentage changes were in favor of bezafibrate (p=0.01). HOMA-BCF values have significantly decreased by 13.9% (p=0.04) in patients of placebo group, whereas in patients of bezafibrate group HOMA-BCF was stable during follow-up and its alterations (-2.9%) were non-significant (p=0.59). CONCLUSIONS: Diabetic patients from the placebo group demonstrated a progressive declining of BCF and an increasing of IR over 2 years of follow-up. These longitudinal changes were attenuated when patients used bezafibrate.

Aged↗

PubMed2006

Renal dysfunction and risk of ischemic stroke or TIA in patients with cardiovascular disease.

BACKGROUND: Mild renal insufficiency is increasingly recognized as an independent risk factor for cardiovascular disease. However, few data exist regarding its relation to risk of ischemic stroke. METHODS: Patients with chronic coronary heart disease and measured serum creatinine levels (n = 6,685) were followed up for incident ischemic stroke or TIA over 4.8 to 8.1 years. Glomerular filtration rate was estimated by the Cockroft-Gault equation and by the four-component Modification of Diet in Renal Disease (MDRD) equation and a rate < or =60 mL/minute/1.73 m2 defined chronic kidney disease (CKD). RESULTS: Among 6,685 patients, a quarter of patients had CKD. Adjusting for conventional risk factors and related medications, patients with CKD exhibited 1.54-fold hazard ratios (95% CI 1.13 to 2.09) of incident ischemic stroke or TIA by the Cockroft-Gault equation (1.53; 95% CI 1.16 to 2.01 by the MDRD equation). The corresponding adjusted hazard ratio associated with an increment of 1 SD in GFR was 0.71 (95% CI 0.57 to 0.88) when estimated by the Cockroft-Gault equation (0.84; 95% CI 0.75 to 0.95 estimated by the MDRD equation). CONCLUSIONS: Mild degrees of renal dysfunction are associated with increased risk of incident ischemic stroke or TIA in patients with pre-existing atherothrombotic disease. These findings expand the recommendation that patients with renal dysfunction should be considered as a high-risk group for cardiovascular disease and for ischemic stroke.

Age Distribution↗

PubMed2006

Hemostatic activation and outcome after recombinant tissue plasminogen activator therapy for acute ischemic stroke.

BACKGROUND AND PURPOSE: Early thrombolytic therapy with intravenous recombinant tissue plasminogen activator (rtPA) improves clinical outcome in acute ischemic stroke (AIS), but impaired endogenous fibrinolysis, thrombin generation, and vascular injury may hamper the efficacy of thrombolysis. We investigated in an exploratory, post hoc analysis the relationship between hemostatic markers and clinical outcomes among patients included in the National Institute of Neurological Disorders and Stroke (NINDS) rtPA Stroke Study. METHODS: Tissue plasminogen activator (tPA) antigen, thrombin-antithrombin complex (TAT), soluble thrombomodulin, and fibrinogen levels were measured in patients with AIS included in the NINDS rtPA Stroke Study from plasma samples collected at baseline, at 2 hours after treatment, and after 24 hours. RESULTS: TAT and tPA antigen levels peaked at 2 hours selectively in the rtPA treatment group, whereas fibrinogen levels dropped at 2 hours and remained low after 24 hours (P<0.0001 for interaction effects between time and treatment). At 24 hours, higher levels of tPA antigen were associated with a lower chance of favorable outcome (odds ratio [OR]=0.34; 95% CI, 0.14 to 0.82) selectively in the rtPA group, and higher levels of TAT (OR=1.72; 95% CI, 1.26 to 2.34) in the entire cohort and of thrombomodulin selectively in the rtPA group (OR=4.45; 95% CI, 1.26 to 15.67) were associated with higher 3-month mortality. CONCLUSIONS: Hemostatic activation after AIS appears to be independently associated with clinical outcome in patients treated with rtPA. However, because we have tested for multiple associations, some may have been identified by chance alone and require further confirmatory studies. On the basis of this exploratory analysis, there is a rationale to investigate the safety and efficacy of protocols in which rtPA is complemented by agents that are antithrombotic and enhance fibrinolysis.

Acute Disease↗

PubMed2006

Serum homocysteine and long-term risk of myocardial infarction and sudden death in patients with coronary heart disease.

We have prospectively evaluated the risk of incident coronary events in association with serum total homocysteine in patients with preexisting chronic coronary heart disease. A nested case-control design was used. Total homocysteine concentration was measured in baseline fasting serum samples from patients with chronic coronary heart disease enrolled in the Bezafibrate Infarction Prevention Study (n = 3,090) who developed coronary events during 6.2 years of follow-up (n = 69). They were matched for age and gender with controls without subsequent cardiovascular events. Elevated homocysteine levels were associated with 2.5 times higher risk of subsequent coronary events and each 5 mumol/l increment was associated with a 25% higher risk.

Bezafibrate↗

PubMed2006

C-reactive protein as a predictor of incident ischemic stroke among patients with preexisting cardiovascular disease.

BACKGROUND AND PURPOSE: C-reactive protein (CRP) has emerged as an important predictor of cardiovascular disease, but there are few prospective data on its association with risk of ischemic stroke in patients at high risk. METHODS: We examined the association between CRP levels and subsequent risk of incident ischemic stroke among 2979 patients with stable coronary heart disease included in a controlled clinical trial (Bezafibrate Infarction Prevention) that assessed the efficacy of bezafibrate, a fibric acid derivative, versus placebo for secondary prevention. CRP was measured by a high-sensitivity assay in plasma samples collected before randomization and again at the second follow-up year of an overall mean follow-up of 6.2 years. RESULTS: Risk of ischemic stroke per 1000 person-years increased from 4.1% for baseline CRP in the lowest tertile (<2.3 mg/L; n=982) to 5.9% for levels at the middle tertile (2.3 to 5.4 mg/L; n=1013) and 10.5% for CRP levels at the upper tertile (>5.4 mg/L; n=984; P<0.001). With adjustment for potential confounders, baseline CRP levels in the top versus bottom tertile were associated with a 2.16-fold increased hazard (95% CI, 1.32 to 3.53) for ischemic stroke, and CRP levels measured after 2 years were associated with a hazard ratio of 2.43 (95% CI, 1.30 to 4.57). The risk of an incident ischemic stroke did not differ between the bezafibrate group compared with the placebo group regardless of baseline CRP levels. CONCLUSIONS: These findings, based on a large prospective study, demonstrate the risk prediction for incident ischemic stroke conferred by CRP levels in patients at high risk.

Aged↗

PubMed2006

Long-term versus intermediate-term supervised exercise training in advanced heart failure: effects on exercise tolerance and mortality.

AIM: To date there have been no studies exploring the effects of long-term versus intermediate-term and short-term supervised exercise training program in patients with severe chronic heart failure (CHF) on optimal medical therapy. We assessed exercise tolerance and mortality in CHF patients undergoing long- versus intermediate-term exercise training (ET). METHODS: Forty-two consecutive severe CHF patients (New York Heart Association functional class III) were referred for a supervised exercise and cardiac rehabilitation program and were followed-up for 3 years: 20/42 (48%) patients discontinued ET after intermediate-term period of 1.6+/-0.8 years (Group A, intermediate-term ET), and 22/42 (52%) remained on the ET program for 3.0+/-0.3 years (Group B, long-term ET). Exercise duration, 6-min walked distance and metabolic equivalents (METs) assessed by modified Bruce protocol were recorded before, 4.5 months after, and 3 years after initiation of ET. RESULTS: Both groups were comparable regarding age, gender, prevalence of ischemic etiology, mean ejection fraction and medications. Risk factors for ischemic heart disease were similar, except for the prevalence of diabetes, which was higher in Group A compared to Group B (11/20 versus 5/22, p=0.03). Significantly more Group A patients died after ET discontinuation (4/20 versus 0/22, p=0.01). At the end of follow-up a significant improvement could be seen in Group B patients compared to A in exercise duration, 6-min walked distance and metabolic equivalents (p<0.01 for all). CONCLUSIONS: Higher survival rate was observed in severe CHF patients undergoing long-term versus intermediate-term exercise training. Long-term supervised exercise training is safe and improves exercise tolerance in these patients.

Exercise Therapy↗

PubMed2006

Interleukin-6 and the risk of future cardiovascular events in patients with angina pectoris and/or healed myocardial infarction.

The aim of this study was to evaluate the prognostic value of interleukin-6 (IL-6) for myocardial infarction (MI) and mortality in a population with stable coronary artery disease (CAD) during a mean period of 6.3 years. IL-6 is a major proinflammatory cytokine of acute phase response; elevated levels are associated with worse prognosis in unstable angina and after acute MI. However, data regarding its long-term prognostic value in stable CAD are limited and controversial. A nested case-control study design was used. Of 3,090 patients with stable CAD, 129 with an adequate blood sample for IL-6 and who reached the end points (MI or sudden death) were randomly selected. Each case was 1:1 matched with 129 controls (alive at the end of the study and free of cardiovascular events) according to age, gender, and treatment. Of the 129 cases, 113 had a MI as the initial event, and for the other 16 the initial event was sudden death. There were 8 patients who first had a MI and later died suddenly. IL-6 was significantly higher in cases (2.34 pg/ml) than in controls (1.65 pg/ml) (p = 0.0004). IL-6 was significantly correlated with C-reactive protein (r = 0.2, p = 0.002); a borderline significance was also found for fibrinogen (r = 0.11, p = 0.07). Each increase of 1 pg/ml in IL-6 was associated with a 1.70 (range 1.23 to 2.45) increased relative odds of subsequent MI or sudden death. Events rate per 1,000 patients-years for the 5 quintiles of IL-6 were 72.26, 89.61, 79.76, 142.53, and 181.08, respectively (p <0.0001). A significantly higher risk in the upper quintile was found (odds ratio, 3.44; 95% confidence interval 1.57 to 8.13). In conclusion, elevated IL-6 levels are strongly associated with future cardiac events and mortality in a population with stable CAD during a long-term follow-up.

Aged↗

PubMed2006

Attenuation of progression of insulin resistance in patients with coronary artery disease by bezafibrate.

BACKGROUND: Development of insulin resistance (IR) may be important in the pathogenesis of both metabolic syndrome and type 2 diabetes mellitus. Few data are available regarding the short-term efficacy of the peroxisome proliferator-activated receptor ligand bezafibrate on IR, and its long-term effect is unknown. The present analysis aimed to investigate the effect of bezafibrate on IR in patients with coronary artery disease enrolled in the Bezafibrate Infarction Prevention Study. METHODS: Metabolic and inflammatory parameters were analyzed from stored frozen plasma samples obtained from patients who completed a 2-year, randomized, double-blind, placebo-controlled study. The homeostatic indexes of IR (HOMA-IRs) were calculated according to the homeostasis model of assessment. RESULTS: Both the patients taking bezafibrate (n = 1262) and those taking placebo (n = 1242) displayed similar baseline characteristics. The HOMA-IRs significantly correlated at baseline and during follow-up with glucose (r = 0.35 and 0.31, respectively) and triglycerides (r = 0.16 and 0.19, respectively). In a subgroup of 351 patients with diabetes, HOMA-IR at baseline was 88% higher than in their counterparts with normal glucose levels (P<.001). In the placebo group, during follow-up there was a significant 34.4% rise in HOMA-IR. In contrast, in the bezafibrate group there was only a nonsignificant 6.6% change in HOMA-IR. The intergroup differences in percentage changes of HOMA-IR were in favor of bezafibrate (P<.001). CONCLUSIONS: In patients with coronary artery disease enrolled in our study, as represented by the placebo group, HOMA-IR increased over time. During the 2 years of the follow-up, bezafibrate significantly attenuated this process.

Aged↗

PubMed2006

Perceptual, social, and behavioral factors associated with delays in seeking medical care in patients with symptoms of acute stroke.

BACKGROUND AND PURPOSE: Despite availability of reperfusion therapy for acute ischemic stroke, most patients remain ineligible mainly because of late hospital arrival. We hypothesized that perceptual, social, and behavioral factors affect delays in seeking help after symptom onset. METHODS: Patients presenting with stroke symptoms were interviewed about symptom experiences, interpretations, and reactions. Odds ratios (95% CI) for risk of delay >3 hours were estimated, and variables associated with increased risk and representing demographic, clinical, perceptual, social, and behavioral factors were included in an assessment of the effect of combined risk factors on delay. RESULTS: Among 209 patients (mean age 61.8+/-12 years, 69% men) the median time interval from symptom awareness to seeking help was 2 (0.5 to 9) hours and to hospital arrival, 4.2 (1.3 to 14.5) hours. On multivariate adjustment, perceiving symptoms as severe (odds ratio [OR]: 0.42; 0.17 to 0.95), advice from others to seek help (OR: 0.18; 0.05 to 0.63), and contacting an ambulance (OR: 0.26; 0.10 to 0.63) were associated with decreased risks of delay, whereas perceived control of symptoms (OR: 2.45; 1.08 to 5.71) increased risk of delay in seeking help. Risk of delay in hospital arrival was 3 times greater in women than in men. Increasing proportions of patients who delayed seeking help were observed with increasing numbers of combined risk factors, ranging from 17% to 94% for 0 to 1 and 6 to 7 factors, respectively. CONCLUSIONS: Perceptual, social, and behavioral factors contribute to delay in seeking medical care in acute ischemic stroke beyond demographic and clinical variables, and, when combined, further increase risk of delay. These findings may be important for designing programs to reduce delay.

Behavior↗

PubMed2006

CD40 ligand and risk of ischemic stroke or coronary events in patients with chronic coronary heart disease.

BACKGROUND: CD40 ligand (CD40L) is a trimeric, transmembrane protein of the tumor necrosis factor family and together with its receptor CD40 is an important contributor to the inflammatory processes that lead to atherosclerosis, plaque destabilization, and thrombosis. METHODS: In order to assess the association between serum concentrations of CD40 ligand (CD40L) and risk of future ischemic stroke and coronary events among patients with chronic CHD, we obtained baseline serum samples from patients (n = 3090) with chronic CHD enrolled in a secondary prevention trial. With a prospective nested case-control design, we measured baseline CD40L concentration in sera of patients who subsequently developed myocardial infarction, sudden cardiac death or ischemic stroke during follow-up (cases, n = 233) and in 233 age- and gender-matched pairs without any subsequent cardiovascular events. RESULTS: Relative odds for recurrent cardiovascular events per one natural log unit difference of CD40L were 0.97 (95%CI, 0.82-1.16). No increase in relative odds for recurrent cardiovascular events was observed per increasing quartiles of CD40L concentrations. In analysis for individual end-points, different trends of risks were observed beyond the 95 percentile for ischemic stroke (OR 2.22; 95%CI, 0.46-12.5) and for recurrent coronary events (OR 0.35; 95%CI, 0.07-1.37), but falling short of statistical significance. CONCLUSION: High serum concentrations of CD40L were not associated with increased risk of ischemic stroke or coronary events in patients with chronic coronary heart disease.

Biomarkers↗

PubMed2006

Serum uric acid and long-term mortality from stroke, coronary heart disease and all causes.

BACKGROUND: Increased serum uric acid (SUA) levels are linked to obesity, dyslipidemia, diabetes and hypertension. Whether SUA carries a risk for coronary heart disease (CHD) and stroke remains uncertain. DESIGN: A prospective cohort study. METHODS: Of an original cohort of middle-aged workers who were examined in 1963 and followed-up for 23 years, 9125 men, free of CHD at entry, are included in this study. Subjects were divided into quintiles according to baseline SUA levels. Hazard ratios (HR) for all-cause, CHD, and stroke mortality were estimated in SUA quintiles, with the third serving as a referent. RESULTS: During follow-up, 2893 deaths were recorded, including 830 ascribed to CHD and 292 to stroke. The HR for all death [1.22, 95% confidence interval (CI) 1.09-1.37] and CHD (1.29, 95% CI 1.05-1.58) were increased in the upper SUA quintile. Fatal stroke showed a U-shaped relationship as both the upper (HR 1.48, 95% CI 1.02-2.17) and bottom (HR 1.43, 95% CI 0.99-2.08) quintiles were associated with a higher risk. Adjustment for confounders reduced the HR of the upper quintile for all outcomes, but did not attenuate the association of the bottom quintile with stroke (HR 1.52, 95% CI 1.04-2.23). When analysed separately by stroke type, the latter association seemed to be stronger for hemorrhagic (HR 3.27, 95% CI 1.14-9.33) than for ischemic stroke (HR 1.34, 95% CI 0.87-2.05). CONCLUSION: In addition to findings supporting increased mortality among hyperuricemic subjects, we identified an association between low SUA levels and fatal stroke, which deserves further investigation.

Biomarkers↗

PubMed2006

Decrease in triglyceride level by bezafibrate is related to reduction of recurrent coronary events: a Bezafibrate Infarction Prevention substudy.

BACKGROUND: Fibrates were reported to be effective in reducing recurrent coronary events in coronary heart disease patients with elevated triglycerides. It is not known whether this effect is related to the extent of triglyceride reduction. METHODS: Participants comprised 3090 coronary heart disease patients enrolled in the Bezafibrate Infarction Prevention study, which showed a nonsignificant reduction (9.4%; P=0.26) in fatal or nonfatal myocardial infarction and sudden death during a mean follow-up time of 6.2 years. RESULTS: Significant reduction in triglyceride serum level was evident only among patients allocated to bezafibrate, ranging between 0.06 mmol/l (5 mg/dl) in the lowest decile of baseline triglycerides level and 0.68 mmol/l (60 mg/dl) in the highest baseline decile. The extent of triglyceride reduction with bezafibrate was significantly associated with the reduction of risk; relative risk reduction of 55% (hazards ratio: 0.45; 95% confidence interval: 0.24-0.84) was observed among patients with baseline triglycerides>or=2.26 mmol/l who reduced triglyceride level to >0.50 mmol/l (>44.3 mg/dl). In contrast, the risk of recurrent events among patients treated with bezafibrate and achieving less triglyceride reduction or failing to reduce triglyceride level was not significantly different from that of patients treated with placebo. CONCLUSION: Bezafibrate treatment was associated with significant risk reduction among coronary heart disease patients with elevated triglyceride levels that substantially reduced their triglyceride level with treatment.

Aged↗

PubMed2006

A national survey of acute cerebrovascular disease in Israel: burden, management, outcome and adherence to guidelines.

BACKGROUND: There are no national data on the burden and management of acute cerebrovascular disease in Israel. OBJECTIVES: To delineate the burden, characteristics, management and outcomes of hospitalized patients with acute cerebrovascular disease in Israel, and to examine adherence to current guidelines. METHODS: We prospectively performed a national survey in all 28 hospitals in Israel admitting patients with acute cerebrovascular events (stroke or transient ischemic attacks) during February and March 2004. RESULTS: During the survey period 2174 patients were admitted with acute cerebrovascular disease (mean age 71 +/- 13 years, 47% women; 89% ischemic stroke or TIA, 7% intracerebral hemorrhage and 4% undetermined stroke). Sixty-two percent of patients were admitted to departments of medicine and a third to neurology, of which only 7% were admitted to departments with a designated stroke unit. Head computed tomography was performed during hospitalization in 93% of patients. The overall rate of urgent thrombolytic therapy for acute ischemic stroke was 0.5%. Among patients with ischemic stroke or TIA, 94% were prescribed an antithrombotic medication at hospital discharge, and among those with atrial fibrillation about half were prescribed warfarin. Carotid duplex was performed in 30% and any vascular imaging study in 36% of patients with ischemic events. The mean (+/-SD) length of hospital stay was 12 +/- 27 days for ICH and 8 +/- 11 days for ischemic stroke. Among patients with ICH, 28% died during hospitalization and 66% died or remained with severe disability while for ischemic stroke the corresponding rates were 7% and 41% respectively. Mortality rates within 3 months were 34% for ICH and 14% for ischemic stroke. CONCLUSIONS: This national survey demonstrates the high burden of acute stroke in Israel and reveals discordance between existing guidelines and current practice. The findings highlight important areas for which reorganization is imperative for patients afflicted with acute stroke.

Acute Disease↗

PubMed2006

[Guidelines for the management of acute stroke--2005].

Stroke is a major cause for morbidity and mortality in Israel, the third most common cause of death and the main cause for neurological disability among adults. Several significant breakthroughs occurred over recent years in the management of stroke, and acute stroke has increasingly been recognized as a medical emergency--a "brain attack" comparable to a "heart attack". Several new scientific publications, guidelines and consensus statements from Europe and North America necessitate a paradigm shift in the management of acute stroke. The guidelines focus on a number of issues: acute stroke as a medical emergency, dedicated stroke units, early reperfusion therapy for acute ischemic stroke, emergency management and general stroke treatment, use of diagnostic tests in the acute phase, and the prevention and treatment of complications.

Acute Disease↗

PubMed2006

Trombolysis in acute stroke.

BACKGROUND: Rapid restoration of cerebral blood flow is the principle goal of acute ischemic stroke therapy. Intravenous recombinant tissue plasminogen activator is an effective therapy for acute ischemic stroke. It has been available in the United States for over a decade and was approved for use in Israel at the end of 2004. OBJECTIVES: To assess the implementation of intravenous rt-PA in routine clinical care at our center after its formal approval in Israel, and the therapeutic and logistic implications for reperfusion therapy for acute ischemic stroke in Israel. METHODS: Patients with acute ischemic stroke admitted between January 2005 and June 2006 who were treated with intravenous rt-PA or endovascular-based reperfusion were reviewed. Implementation, timing, safety and clinical outcomes were assessed. RESULTS: Forty-six patients received reperfusion therapy (37 with intravenous rt-PA and 9 with endovascular-based therapy), corresponding to 4.0% of ischemic stroke patients in 2005 and a projection of 6.2% in 2006. The mean age of intravenously treated patients was 67 years (range 22-85 years), median baseline NIHSS score was 14 (25-75%, 10-18) and the median 'onset to drug time' was 150 minutes (25-75%, 120-178). Symptomatic intracerebral hemorrhage and orolingual angioedema each occurred in one patient (2.7%). Significant clinical improvement occurred in 54% of treated patients, and 38% of patients were independent at hospital discharge. CONCLUSIONS: The use of reperfusion therapy for acute ischemic stroke has increased in our center after the formal approval of rt-PA therapy to over 5%, with 'onset to drug time', safety and outcome after intravenous rt-PA treatment comparing favorably with worldwide experience. A prerequisite for the implementation of effective reperfusion therapy and expansion of the proportion of patients treated nationwide is the establishment of a comprehensive infrastructure.

Adult↗

PubMed2005

Hemodynamic evaluation of embolic trajectory in an arterial bifurcation: an in-vitro experimental model.

BACKGROUND AND PURPOSE: Despite the importance of embolism as a major cause of brain infarction, little is known about the hemodynamic factors governing the path large emboli tend to follow. Our aim was to test in vitro, whether hemodynamic parameters other than flow ratios between bifurcation branches may affect the distribution of embolic particles in a Y-shaped bifurcation model, used as an analogue to an arterial bifurcation. METHODS: In vitro experiments were conducted using suspensions of sphere-shaped particles (0.6, 1.6, and 3.2 mm) in water-glycerin mixture, using steady and pulsatile laminar flow regimes in a Y-shaped bifurcation model (identical branching angles [theta1=theta2=45 degrees] with one daughter branch diameter wider than the other [D1=6 mm, D2=4 mm]; average Reynolds number 500). RESULTS: Experiments using naturally buoyant particles under steady flow conditions and four outlet-flow ratios revealed that small (0.6 mm) and mid-sized (1.6 mm) particles entered into either the narrower or wider bifurcation daughter branch nonpreferentially, proportionally to the flow ratios. Large particles (3.2 mm), however, preferentially entered the wider daughter branch. Moreover, as the flow ratio increases this phenomenon was augmented. Further experiments revealed that the preference of the wider daughter branch for high particle-to-branch diameter-ratios further increases under pulsatile flow and by the density ratio between particles and fluid. CONCLUSIONS: Particles' distribution in a bifurcation is affected, beyond its outlets-flow-ratios, by the particle-to-branch diameter-ratio. The tendency of large particles to preferentially enter the wider bifurcation branch, beyond the flow ratio, is augmented under pulsatile flow conditions and is affected by particle-to-fluid density-ratio. These findings may have important implications for understanding the hemodynamic mechanisms underlying the trajectory of large emboli.

Animals↗