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D Simard

Publications and source records attributed to D Simard.

At least 19 recordsLinked to original sources
PubMed1999

Low-dose and high-dose acetylsalicylic acid for patients undergoing carotid endarterectomy: a randomised controlled trial. ASA and Carotid Endarterectomy (ACE) Trial Collaborators.

BACKGROUND: Endarterectomy benefits certain patients with carotid stenosis, but benefits are lessened by perioperative surgical risk. Acetylsalicylic acid lowers the risk of stroke in patients who have experienced transient ischaemic attack and stroke. We investigated appropriate doses and the role of acetylsalicylic acid in patients undergoing carotid endarterectomy. METHODS: In a randomised, double-blind, controlled trial, 2849 patients scheduled for endarterectomy were randomly assigned 81 mg (n=709), 325 mg (n=708), 650 mg (n=715), or 1300 mg (n=717) acetylsalicylic acid daily, started before surgery and continued for 3 months. We recorded occurrences of stroke, myocardial infarction, and death. We compared patients on the two higher doses of acetylsalicylic acid with patients on the two lower doses. FINDINGS: Surgery was cancelled in 45 patients, none were lost to follow-up by 30 days, and two were lost by 3 months. The combined rate of stroke, myocardial infarction, and death was lower in the low-dose groups than in the high-dose groups at 30 days (5.4 vs 7.0%, p=0.07) and at 3 months (6.2 vs 8.4%, p=0.03). In an efficacy analysis, which excluded patients taking 650 mg or more acetylsalicylic acid before randomisation, and patients randomised within 1 day of surgery, combined rates were 3.7% and 8.2%, respectively, at 30 days (p=0.002) and 4.2% and 10.0% at 3 months (p=0.0002). INTERPRETATION: The risk of stroke, myocardial infarction, and death within 30 days and 3 months of endarterectomy is lower for patients taking 81 mg or 325 mg acetylsalicylic acid daily than for those taking 650 mg or 1300 mg.

Aged↗
PubMed1999

Myocardial blood flow regulation relative to left ventricle pressure and volume in anesthetized dogs.

The influence of left ventricle pressure and volume changes on coronary blood flow was investigated in eight anesthetized dogs. Coronary artery pressure-flow relationships were determined at two levels of left ventricular pressure and volume. The distribution of blood flow within the myocardium was also determined when these relationships varied. Reducing left ventricle pressures and volumes increased heart rate. Rate-pressure product, diastolic coronary pressure, myocardial O2 consumption, total, subendocardial and subepicardial flow decreased. Hematocrit and blood gas data were unchanged. The pressure-flow relationships were shifted leftward (p = 0.001) but the range of autoregulation was not altered. At low left ventricle pressures and volumes, the lower coronary artery pressure limit was shifted leftward (from 75 to 45 mm Hg (1 mm Hg = 133.3 Pa)), while total, subendocardial, and subepicardial blood flow did not change compared with the control. Below the lower coronary artery pressure limit, subendocardial but not subepicardial flow decreased, resulting in maldistribution of flow across the left ventricular wall. When coronary pressure was reset between control and the lower coronary artery pressure limit, subendocardial flow was restored. These results show that the lower coronary artery pressure limit can be shifted leftward while the distribution of blood flow across the left ventricular wall is preserved.

Anesthesia↗
PubMed1998

Canadian guidelines for intravenous thrombolytic treatment in acute stroke. A consensus statement of the Canadian Stroke Consortium.

BACKGROUND: The thromobolytic drug, tissue plasminogen activator (tPA) has been approved in the United States for the treatment of acute ischemic stroke amid controversy and concern about the balance of risk and benefit. The Canadian Stroke Consortium (CSC), a national network of neurologists who collaborate on joint projects in stroke medicine, including clinical trials and consensus statements, has developed guidelines for the use of tPA in Canada. METHODS AND RESULTS: The CSC Board of Directors wrote a preliminary report based on existing publications, including randomized drug trials and the report of a special committee struck by the Stroke Council of the American Heart Association. This draft was circulated to the CSC membership-at-large for suggestions or amendments, to produce this final draft. CONCLUSIONS: The present guidelines have been devised to represent a Canadian viewpoint of management. The Health Protection Branch of the Ministry of Health of Canada has not yet produced an evaluation. Further modification of these guidelines may be necessary when more data from clinical trials and experience with the drug become available.

Acute Disease↗
PubMed1997

AMF-R tubules concentrate in a pericentriolar microtubule domain after MSV transformation of epithelial MDCK cells.

Autocrine motility factor receptor (AMF-R) is localized to an intracellular microtubule-associated membranous organelle, the AMF-R tubule. In well-spread untransformed MDCK epithelial cells, the microtubules originate from a broad perinuclear region and AMF-R tubules extend throughout the cytoplasm of the cells. In Moloney sarcoma virus (mos)-transformed MDCK (MSV-MDCK) cells, microtubules accumulate around the centrosome, forming a microtubule domain rich in stabilized detyrosinated microtubules. AMF-R tubules are quantitatively associated with this pericentriolar microtubule domain and the rough endoplasmic reticulum and lysosomes also co-distribute with the pericentriolar mass of microtubules. The Golgi apparatus is closely associated with the microtubule organizing center (MTOC) within the juxtanuclear mass of AMF-R tubules, and no co-localization of AMF-R tubules with the Golgi marker beta-COP could be detected by confocal microscopy. After nocodazole treatment and washout, microtubule nucleation occurs exclusively at the centrosome of MSV-MDCK cells, and only after microtubule extension to the cell periphery does the microtubule cytoskeleton reorganize to generate the pericentriolar microtubule domain after 30-60 min. AMF-R tubules dispersed by nocodazole treatment concentrate in the pericentriolar region in parallel with the reorganization of the microtubule cytoskeleton. MSV transformation of epithelial MDCK cells results in the stabilization of a pericentriolar microtubule domain responsible for the concentration and polarized distribution of AMF-R tubules.

Animals↗
PubMed1997

Outcome of asymptomatic patients with carotid disease. Asymptomatic Cervical Bruit Study Group.

Asymptomatic cervical atherosclerosis carries a variable risk of vascular events. We sought to identify patients with asymptomatic cervical bruits who may be at increased risk of developing ischemic events. We conducted a prospective multicenter cohort study of neurologically asymptomatic patients presenting a cervical bruit. Patients had biannual neurologic and carotid duplex evaluation. Association between ultrasonographic findings and vascular events, adjusting for common risk factors, was evaluated. Seven hundred fifteen patients were followed on average for 3.6 years. Mean age was 65 years. At initial visit, 357 subjects had a > or = 50% stenosis. Overall, 237 events occurred in 177 patients. Annual rate of all primary vascular events in patients with > or = 50% stenosis was 11.0% versus 4.2% in those with < 50% stenosis (p < 0.001). Annual rate of stroke and vascular death was 5.5% in the > or = 50% group compared with 1.9% in the < 50% group (p < 0.001). Yearly rate of unheralded ischemic stroke was 4.2% in subjects with > or = 80% stenosis and 1.4% in those with stenosis < 80% (p < 0.001). A stroke or TIA was ipsilateral to a > or = 80% stenosis in 66% of patients. Progression of carotid stenosis particularly to more than 80% was associated both with a higher rate of ipsilateral neurologic events and overall combined vascular events. Our data suggest that severity of carotid stenosis is the main risk factor predicting occurrence of neurologic and other vascular events. Yearly rate of ipsilateral stroke with > or = 50% carotid stenosis is low (1.4%) and most are nondisabling. Progression to > or = 80% or occlusion is associated with worse outcome.

Aged↗
PubMed1996

Inverse relation of autocrine motility factor receptor and E-cadherin expression following MDCK epithelial cell transformation.

Autocrine motility factor interacts with its cell surface receptor (AMF-R) to stimulate tumor cell motility. To study AMF-R expression following transformation of polarized epithelial MDCK cells, we have used the invasive Moloney sarcoma virus transformed MDCK (MSV-MDCK) cell population. Decreased E-cadherin expression of the transformed MSV-MDCK clones is associated with both increased cellular motility and increased AMF-R expression. Increased AMF-R expression is due to MSV transformation as differentially motile MSV-MDCK clones, which either retain low E-cadherin, exhibit equivalent high levels of AMF-R. Loss of the polarized epithelial phenotype and increased cellular motility following transformation of MDCK cells is thus associated with a shift from a high E-cadherin/low AMF-R to a low E-cadherin/low AMF-R phenotype.

Animals↗
PubMed1996

Alniditan in the acute treatment of migraine attacks: a subcutaneous dose-finding study. Subcutaneous Alniditan Study Group.

Alniditan is a new 5HT1D receptor agonist, belonging to a different chemical class from sumatriptan and other indole derivatives used or being developed for the treatment of acute migraine. In a multinational double-blind randomized parallel-groups dose-finding trial, alniditan was given subcutaneously in hospital to patients with migraine headache of moderate or severe intensity at doses of 0.8 mg (n = 44), 1.0 mg (n = 42), 1.2 mg (n = 46) and 1.4 mg (n = 39). Efficacy, tolerability and safety of each dose were compared with those of placebo (n = 41). At 2 h after injection, headache was absent or mild in 83% and 82% of patients receiving alniditan 1.2 and 1.4 mg respectively compared with 39% for placebo (p < or = 0.002). Complete relief from headache was achieved in 72% (1.4 mg). Time to onset of relief decreased with increasing alniditan dose, and there was a dose-dependent reduction in headache recurrence rate: 25% of patients receiving 1.4 mg had responded by 15 min and headache recurred within 24 h in only 16% of the patients who initially responded to alniditan 1.4 mg, significantly less than for placebo (p = 0.018). Alniditan was superior to placebo in reducing the associated symptoms of nausea, phonophobia and photophobia, and in increasing patients' functional ability. The use of rescue medication was reduced when compared with placebo, and up to 87% of patients said that they would use the drug again if available. No clinically relevant cardiovascular effects were seen, nor consistent changes in clinical laboratory findings. Adverse effects, mainly head pressure, paraesthesia, and hot flushes, were reported by 34% of placebo-treated patients and up to 70% of patients receiving alniditan, but all doses were very well tolerated and no clear relationship with dose was established. Comparison with published findings suggests that alniditan 1.4 mg sc may have advantages over sumatriptan 6 mg sc in providing complete relief from acute migraine headache, and may be associated with fewer headache recurrences within 24 h. Both of these suggestions warrant further and larger trials of alniditan in acute migraine.

Adult↗
PubMed1996

Effect of 3-aminotriazole on hyperthermia-mediated cardioprotection in rabbits.

Hyperthermia-induced cardioprotection during myocardial ischemia may involve increased activity of antioxidative enzymes. In this study we investigated the effects of 3-amino-1,2,4-triazole (3-AT), an irreversible catalase inhibitor, in heat-shocked (HS) rabbits subjected to ischemia-reperfusion injury. Rabbits underwent whole body hyperthermia at 42 degrees C for 15 min. Twenty-four hours later, rabbits were administered either saline vehicle or 3-AT (1 or 2 g/kg i.p.) 30 min before undergoing 30 min of regional coronary occlusion and 3 h reperfusion. Controls did not undergo whole body hyperthermia and were given either saline or 3-AT. Heart rate and left ventricular pressure were recorded continuously during these experiments. Infarct area (tetrazolium staining) was normalized to anatomic risk zone size (microsphere autoradiography). Expression of HSP 71 was verified using Western blot analysis; myocardial catalase activity was determined in tissue biopsies. Infarct size was significantly reduced in HS rabbits (25.1 +/- 2.8%, P = 0.2; means +/- SE) compared with controls (53.6 +/- 4.7%). Treatment with 1 g/kg 3-AT attenuated HS-mediated cardioprotection (36.9 +/- 4.9%, P = 0.063 vs. HS); protection was abolished with 2 g/kg 3-AT (48.9 +/- 6.6%). Myocardial catalase activities were higher in tissue biopsies from HS rabbits (47.0 +/- 4.5 U/mg protein, P < or = 0.02) compared with controls (33.4 +/- 1.9 U/mg protein); catalase activities were significantly reduced in rabbits treated with 3-AT. In conclusion, whole body hyperthermia increases expression levels of HSP 71; myocardial catalase activity is also significantly increased. Myocardial protection is HS rabbits subjected to ischemia-reperfusion injury was reversed with 3-AT. These data suggest that increased intracellular activities of catalase and possibly other antioxidant enzymes is an important mechanism for hyperthermia-mediated cellular protection.

Amitrole↗
PubMed1995

The risk of stroke in patients with first-ever retinal vs hemispheric transient ischemic attacks and high-grade carotid stenosis. North American Symptomatic Carotid Endarterectomy Trial.

BACKGROUND: The prognosis of amaurosis fugax has been considered to be favorable compared with that of hemispheric transient ischemic attacks. However, this has remained uncertain for patients with significant carotid stenosis as the assessment of progression of the disease has been confounded when patients undergo carotid endarterectomy. In the North American Symptomatic Carotid Endarterectomy Trial, patients with high-grade (70% to 99%) carotid stenosis were randomized to receive either medical or surgical treatment, thus making an unconfounded analysis possible. METHOD: We identified 129 medically treated patients with high-grade carotid stenosis who had their first-ever transient ischemic attack as the entry event into the trial. Fifty-nine patients with retinal transient ischemic attacks (RTIAs) were compared with 70 patients with hemispheric transient ischemic attacks (HTIAs). RESULTS: Patients with HTIAs were older, with a higher prevalence of most risk factors for stroke. Average time of delay from the onset of transient ischemic attacks to medical treatment was longer for patients with RTIAs than for patients with HTIAs (48.5 vs 15.2 days). Kaplan-Meier estimates of the risk of ipsilateral stroke at 2 years were 16.6% +/- 5.6% for patients with RTIAs and 43.5% +/- 6.7% for patients with HTIAs (P = .002 for the difference in risk between RTIAs and HTIAs). From corresponding Cox's proportional hazards regression analyses, the risk of ipsilateral stroke ranged from 11.2% to 28.9% for patients with RTIAs and from 37.4% to 96.3% for patients with HTIAs across stenoses, spanning 75% to 95%. Overall, the relative risk of ipsilateral stroke (HTIAs compared with RTIAs) was 3.23 (95% confidence interval, 1.47 to 7.12), regardless of the degree of high-grade stenosis. CONCLUSION: To our knowledge, this study is the first report on the expected outcome for medically treated patients with high-grade (70% to 99%) carotid stenosis in whom the first-ever event was either an RTIA or HTIA. The presence of RTIAs carries a considerable risk of ipsilateral strokes, particularly at higher degrees of stenosis. However, in comparison with HTIAs, patients with RTIAs still have a better prognosis.

Aged↗
PubMed1995

Autocrine motility factor receptor is a marker for a distinct membranous tubular organelle.

Autocrine motility factor (AMF) is secreted by tumor cells and is capable of stimulating the motility of the secreting cells. In addition to being expressed on the cell surface, its receptor, AMF-R, is found within a Triton X-100 extractable intracellular tubular compartment. AMF-R tubules can be distinguished by double immunofluorescence microscopy from endosomes labeled with the transferrin receptor, lysosomes labeled with LAMP-2, and the Golgi apparatus labeled with beta-COP. AMF-R can also be separated from a LAMP-2 containing lysosomal fraction by differential centrifugation of MDCK cells and is found within a 100,000 g membrane pellet. By electron microscopic immunocytochemistry, AMF-R is localized predominantly to smooth vesicular and tubular membranous organelles as well as to a lesser extent to the plasma membrane and rough endoplasmic reticulum. AMF-R tubules have a variable diameter of 50-250 nm and can acquire an elaborate branched morphology. By immunofluorescence microscopy, AMF-R tubules are clearly distinguished from the calnexin labeled rough endoplasmic reticulum and AMF-R tubule expression is stable to extended cycloheximide treatment. The AMF-R tubule is therefore not a biosynthetic subcompartment of the endoplasmic reticulum. The tubular morphology of the AMF-R tubule is modulated by both the actin and microtubule cytoskeletons. In a similar fashion to that described previously for the tubular lysosome and endoplasmic reticulum, the linear extension and peripheral cellular orientation of the AMF-R tubule are dependent on the integrity of the microtubule cytoskeleton. The AMF-R tubule may thus form part of a family of microtubule-associated tubular organelles.

Animals↗
PubMed1995

CNS vasculitis.

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Central Nervous System Diseases↗
PubMed1994

Timely administration of AICA riboside reduces reperfusion injury in rabbits.

OBJECTIVE: Agents which promote increased interstitial adenosine levels may be cardioprotective. The aim of this study was to evaluate the ability of 5-amino-1-beta-D- ribofuranosylimidazole-4-carboxamide (AICAr), an adenosine regulating agent, to limit infarct size when given before ischaemia, before coronary reperfusion, or postreperfusion in a rabbit preparation of ischaemia-reperfusion injury. METHODS: The left coronary artery was occluded for 30 min and subsequently the ischaemic bed was reperfused for 180 min. Infarct size and risk zone size were delineated by tetrazolium staining and microsphere autoradiography, respectively. Four groups were studied: controls (n = 13), AICAr (2.5 mg.kg-1.min-1 intravenously for 5 min followed by 0.5 mg.kg-1.min-1 for 60 min) beginning either 5 min before coronary occlusion (n = 11), 5 min before coronary reperfusion (n = 11), or at 25 min coronary reperfusion (n = 10). Lignocaine was not given in these experiments. RESULTS: Infarct size, normalised to risk zone, was significantly reduced with AICAr given 5 min before coronary reperfusion, at 35.0(SEM 4.4)% v 51.8(3.9)% in controls; p = 0.03. Cardioprotection was not observed when AICAr was given either 5 min before coronary occlusion [44.2(4.8)%] or 25 min postreperfusion [45.9(3.2)%]. CONCLUSIONS: These findings support the hypothesis that adenosine regulating agents, such as AICAr, can modulate infarct size in this rabbit preparation of ischaemia-reperfusion injury.

Aminoimidazole Carboxamide↗
PubMed1992

Comparison of the efficacy and safety of flunarizine to propranolol in the prophylaxis of migraine.

This study was designed to compare flunarizine, a cerebro-specific calcium channel antagonist, and propranolol in the prophylaxis of migraine with or without aura. Following a 1 month single-blind placebo baseline period, 94 patients were equitably randomised under double-blind conditions to take flunarizine 10 mg daily or propranolol 80 mg twice daily for 4 months. Both treatments led to a significant reduction in the frequency of migraines and use of rescue analgesics with a significantly greater decrease in number of attacks for flunarizine after 1 and 4 months. Neither treatment affected the severity nor duration of migraines. Overall, 67% of flunarizine patients and 51% of propranolol patients responded positively. Propranolol significantly reduced blood pressure and heart rate; flunarizine had no effect on cardiovascular function. Weight gain was noted with both treatments. Flunarizine is at least as effective as propranolol in the prophylactic treatment of migraine and may have a better safety profile.

Adolescent↗
PubMed1975

Carotid endarterectomy: survival rates of 227 patients.

From March 1963 to March 1974, 227 patients with carotid stenosis underwent unilateral or bilateral carotid endarterectomy at l'Hôpital de l'Enfant-Jésus in Québec. Survival during the first 7 years after operation was analysed by life-table methods based on full intervals. The observed probability of death in this group was significantly higher than the probability expected in the general population, by 6.8% in the 1st year and 3.9% in the 2nd year. In the next 3 years the differences were much smaller (0.5, 0.9 and 1.4%). The major causes of death were myocardial infarction and stroke. Women fared somewhat better than men after the 1st year of follow-up. Unexpectedly, patients who underwent unilateral endarterectomy had lower survival rates in each of the first 5 years after operation than patients who underwent staged bilateral operations, whether survival was measured from the date of the first or the second operation.

Adult↗