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Biomedical subjects

C Graffagnino

Publications and source records attributed to C Graffagnino.

16 recordsLinked to original sources
PubMed2003

Effect of apolipoprotein E genotype on in-hospital mortality following intracerebral haemorrhage.

OBJECTIVE: To determine the relationship between the apolipoprotein E (APOE) epsilon4 allele and in-hospital mortality from intracerebral haemorrhage (ICH). MATERIAL AND METHODS: Patients admitted to two acute stroke units with ICH were prospectively evaluated and APOE genotyped. In-hospital survival was recorded in 176 patients. RESULTS: There were 85 men and 91 women, mean age 68 years. Fifty-two (30%) of the 176 patients died in hospital. After adjusting for sex, age, hospital, and race, increased age (P = 0.009) and the presence of the APOEepsilon4 allele (P = 0.026) significantly reduced in-hospital survival. CONCLUSION: The APOEepsilon4 allele in this population may be associated with poor survival following ICH.

Age Distribution↗
PubMed2001

Feasibility and safety of moderate hypothermia after massive hemispheric infarction.

BACKGROUND AND PURPOSE: Moderate hypothermia decreases ischemic damage in experimental stroke models. This multicenter study was performed to evaluate (1) the safety and feasibility of moderate hypothermia and (2) its potential to reduce intracranial hypertension in acute stroke patients. METHODS: Fifty prospective patients with cerebral infarction involving at least the complete middle cerebral artery territory treated with moderate hypothermia were evaluated. Hypothermia was induced with the use of cooling blankets as well as alcohol and ice bags within 22+/-9 hours after stroke onset and maintained for 24 to 72 hours; subsequently, patients passively rewarmed over a mean duration of 17 hours. Outcome was assessed at 4 weeks and at 3 months. RESULTS: Time required for cooling to <33 degrees C varied from 3.5 to 11 hours. The most frequent complications of hypothermic therapy were thrombocytopenia (70%), bradycardia (62%), and pneumonia (48%). Four patients (8%) died during hypothermia as a result of severe coagulopathy, cardiac failure, or uncontrollable intracranial hypertension. An additional 15 patients (30%) died during or after rewarming because of rebound increase in intracranial pressure (ICP) and fatal herniation. A shorter (<16 hours) rewarming period was associated with a more pronounced rise of ICP. Elevated ICP values were significantly reduced under hypothermia. Neurological outcome according to the National Institutes of Health Stroke Scale score 4 weeks after stroke was 29, and Rankin Scale score 3 months after stroke was 2.9. CONCLUSIONS: Moderate hypothermia is feasible in patients with acute stroke, although it is associated with several side effects. Most deaths occur during rewarming as a result of excessive ICP rise. Our preliminary observation that a longer duration of the rewarming period limits the ICP increase remains to be confirmed in future studies.

Acute Disease↗
PubMed2000

Dose-finding, safety, and tolerability study of an oral platelet glycoprotein IIb/IIIa inhibitor, lotrafiban, in patients with coronary or cerebral atherosclerotic disease.

BACKGROUND: Antiplatelet therapy is the mainstay of the treatment and secondary prevention of cardiovascular and cerebrovascular ischemic events. We assessed the safety, tolerability, and pharmacodynamics of lotrafiban, an oral platelet glycoprotein IIb/IIIa inhibitor, as a secondary prevention strategy in patients with cerebrovascular or cardiovascular disease. METHODS AND RESULTS: Overall, 451 patients with a recent cardiovascular or cerebrovascular acute ischemic event were randomized in a double-blind fashion to 1 of 5 dosing regimens for 12 weeks: placebo or 5, 20, 50, or 100 mg lotrafiban, both twice daily with 300 to 325 mg/d aspirin. The primary end point was the incidence and tolerability of major and minor bleeding during treatment. Secondary end points included inhibition of platelet aggregation and clinical events. The placebo and lotrafiban 5-mg groups had similarly low rates of minor and major bleeding, but the 100-mg arm was terminated early because of excess major bleeding. Protocol-defined thrombocytopenia (<100 000 platelets/microL) occurred in 5 lotrafiban-treated patients (1.4%, 95% CI 0.2% to 2.7%) and 1 placebo patient (1.1%, 95% CI 0% to 3.1%). Three lotrafiban-treated patients had a nadir platelet count <20 000/microL (0.9%, 95% CI 0% to 1.8%). Lotrafiban produced dose-dependent inhibition of platelet aggregation; 5 mg lotrafiban did not differ significantly from placebo, whereas 100 mg inhibited aggregation by nearly 100%. CONCLUSIONS: -Lotrafiban provides dose-dependent platelet inhibition when administered to a range of patients with atherosclerosis. The level of platelet inhibition appears to correlate with bleeding risk and drug tolerability.

Administration, Oral↗
PubMed2000

Design of the blockade of the glycoprotein IIb/IIIa receptor to avoid vascular occlusion (BRAVO) trial.

BACKGROUND: Platelets play a key role in the pathogenesis of atherosclerosis, thrombosis, and acute coronary and cerebrovascular syndromes. Inhibition of platelet function by acetylsalicylic acid (aspirin) has been shown to reduce the incidence atherothrombotic events in patients with coronary, cerebrovascular, or peripheral vascular disease. Thienopyridine agents, however, including ticlopidine and clopidogrel, inhibit the adenosine diphosphate receptor and have modestly superior effects compared with aspirin on reduction of death, myocardial infarction, and stroke among a broad group of patients with vascular disease. More effective antithrombotic agents are still required to treat patients at high risk for recurrent vascular events. METHODS: Lotrafiban, a selective, nonpeptide antagonist of the human platelet fibrinogen receptor (glycoprotein [GP] IIb/IIIa [alphaIIb/beta3 integrin]), blocks the binding of fibrinogen to the GP IIb/IIIa receptor, which is the final common pathway of platelet aggregation. Lotrafiban at doses of up to 50 mg twice daily was well-tolerated in a 12-week, double-blind, placebo-controlled, dose-ranging study in patients with recent myocardial infarction, unstable angina, transient ischemic attack, or stroke when added to aspirin therapy. On the basis of these results, a dosing regimen was selected for the phase III Blockage of the Glycoprotein IIb/IIIa Receptor to Avoid Vascular Occlusion (BRAVO) trial based on pharmacodynamics and drug tolerability. In the pivotal BRAVO study, lotrafiban therapy is being evaluated in patients who have had a recent myocardial infarction, unstable angina, transient ischemic attack, or ischemic stroke, or who present at any time after a diagnosis of peripheral vascular disease combined with either cardiovascular or cerebrovascular disease. RESULTS: The efficacy evaluation will be based on a composite end point of clinical events (death by any cause, myocardial infarction, stroke, recurrent ischemia requiring hospitalization, or urgent ischemia-driven revascularization). The target enrollment is 9200 patients worldwide. Approximately 700 centers will participate and will be distributed within 30 countries across North America, Europe, Australia, and Asia.

Administration, Oral↗
PubMed1999

Stroke in patients with acute coronary syndromes: incidence and outcomes in the platelet glycoprotein IIb/IIIa in unstable angina. Receptor suppression using integrilin therapy (PURSUIT) trial. The PURSUIT Investigators.

BACKGROUND: The incidence of stroke in patients with acute coronary syndromes has not been clearly defined because few trials in this patient population have been large enough to provide stable estimates of stroke rates. METHODS AND RESULTS: We studied the 10 948 patients with acute coronary syndromes without persistent ST-segment elevation who were randomly assigned to placebo or the platelet glycoprotein IIb/IIIa receptor inhibitor eptifibatide in the Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy (PURSUIT) trial to determine stroke rates, stroke types, clinical outcomes in patients with stroke, and independent baseline clinical predictors for nonhemorrhagic stroke. Stroke occurred in 79 (0.7%) patients, with 66 (0.6%) nonhemorrhagic, 6 intracranial hemorrhages, 3 cerebral infarctions with hemorrhagic conversion, and 4 of uncertain cause. There were no differences in stroke rates between patients who received placebo and those assigned high-dose eptifibatide (odds ratios and 95% confidence intervals 0.82 [0.59, 1.14] and 0.70 [0.49, 0.99], respectively). Of the 79 patients with stroke, 17 (22%) died within 30 days, and another 26 (32%) were disabled by hospital discharge or 30 days, whichever came first. Higher heart rate was the most important baseline clinical predictor of nonhemorrhagic stroke, followed by older age, prior anterior myocardial infarction, prior stroke or transient ischemic attack, and diabetes mellitus. These factors were used to develop a simple scoring nomogram that can predict the risk of nonhemorrhagic stroke. CONCLUSIONS: Stroke was an uncommon event in patients with acute coronary syndromes in the PURSUIT trial. These strokes are, however, associated with substantial morbidity and mortality rates. The majority of strokes were of nonhemorrhagic causes. Eptifibatide was not associated with an increase in intracranial hemorrhage, and no significant effect on nonhemorrhagic stroke was observed. We developed a useful nomogram for assigning baseline nonhemorrhagic stroke risk in this patient population.

Acute Disease↗
PubMed1997

Endoglin gene polymorphism as a risk factor for sporadic intracerebral hemorrhage.

Intracerebral hemorrhage (ICH) is a common and serious type of stroke. Recent studies have shown that inherited factors that affect the development of the vessel wall can increase the risk of ICH. We studied endoglin as a candidate gene in patients with sporadic ICH, since mutations in this gene can cause telangiectasia formation. One hundred three patients with sporadic ICH and 202 controls were studied. The polymerase chain reaction and single-strand conformational polymorphism analysis were used to screen for mutations in exon 7 of the endoglin gene. No coding mutations in exon 7 were identified in the ICH patients or controls. A 6-base intronic insertion was found 26 bases beyond the 3' end of exon 7. The homozygous form of the insertion was present in 9 of 103 (8.7%) ICH patients compared with 4 of 202 (2.0%) controls, p = 0.012 (odds ratio 4.8 [95% confidence interval, 1.28, 21.60]). Analysis of the endoglin transcript around the insertion did not reveal any changes in the RNA sequence. There were no obvious clinical features that distinguished the ICH patients with the homozygous insertion from the other patients. The pathophysiologic mechanism underlying this association remains to be determined.

Adult↗
PubMed1997

Tissue plasminogen activator in a vertebral artery dissection.

BACKGROUND: Spontaneous dissection of the vertebral artery is uncommon. METHOD: Case study. RESULTS: We report a 49-year-old woman who presented with the rapidly progressing basilar artery syndrome who was given an intravenous dose of tissue plasminogen activator seven hours after the onset of first symptoms. Thirty minutes after the injection, a dramatic recovery of the patient's consciousness and neurological signs was noted. CONCLUSION: To our knowledge, this is the first reported case of intravenous tissue plasminogen activator use in acute vertebral artery dissection.

Arterial Occlusive Diseases↗
PubMed1996

Lipids and stroke: a paradox resolved.

BACKGROUND: Although dyslipidemia is a well established risk factor for coronary artery disease, its relationship to ischemic cerebrovascular disease has remained unclear, perhaps because of the heterogeneous nature of strokes. METHODS: In a case-control study, we measured the serum concentrations of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, serum triglycerides, and lipoprotein(a) levels and determined the apolipoprotein E phenotype and serum ferritin level in 90 consecutive systematically investigated patients with stroke or transient ischemic attack of atherothrombotic origin. Ninety age-, sex-, and community-matched subjects served as controls. RESULTS: Plasma total cholesterol (5.99 vs 5.45 mmol/L [232 vs 211 mg/dL], P=.003), low-density lipoprotein cholesterol (3.96 vs 3.45 mmol/L [153 vs 133 mg/dL], P=.004), and serum triglyceride (2.09 vs 1.82 mmol/L [8] vs 70 mg/dL], P=.03) levels were significantly higher among the patients with atherothrombotic strokes and transient ischemic attacks than among the control subjects. The inverse was true for high-density lipoprotein cholesterol (1.07 vs 1.18 mmol/L [41 vs 46 mg/dL], P=.02) levels. No significant differences were found in lipoprotein(a) levels or in the distribution of apolipoprotein E phenotypes or allele frequency. Serum ferritin levels did not differ significantly between patients and control subjects. CONCLUSIONS: Elevated low-density lipoprotein cholesterol and triglyceride levels are significant independent risk factors in patients with proven atherothrombotic cerebrovascular disease manifesting as stroke or transient ischemic attack. The level of stored serum iron, as reflected by serum ferritin levels, does not correlate with the presence of atherothrombotic cerebrovascular or coronary disease.

Aged↗
PubMed1995

Risk of intracranial aneurysms in families with subarachnoid hemorrhage.

BACKGROUND: Genetic factors may be important in the etiology of subarachnoid hemorrhage (SAH) and intracranial aneurysm (IA) formation. Several studies have reported the familial occurrence of SAH and IA, although in most cases asymptomatic family members were not studied with elective angiography. The examination of data from large sibships could provide important information about the frequency of IA occurrence in at-risk individuals and the mode of inheritance for familial SAH/IA. METHODS: We reviewed published case series of sibships with SAH and at least four siblings, in which at least one sibling underwent elective angiography. Data were collected on age-of-onset, clinical events, presence of hypertension, angiographic findings, and outcome. Patients were classified as "affected" if they had a SAH or if an IA was detected by elective angiography, and "unaffected" if they were asymptomatic and had a negative angiogram. RESULTS: Seven case series with 52 individuals (26 men and 26 women) met our inclusion criteria. The sibships ranged from 6 to 13 members. Most of the siblings (32 of 52, 61%) were asymptomatic, 18 (35%) had a SAH, and 2 (4%) had focal symptoms but no SAH. Elective angiography of 34 siblings showed an IA in 11 (32%) and was negative in 23 (68%). The overall rate of affecteds (SAH or IA) was 56%. CONCLUSIONS: Based on data from these sibships, angiography of asymptomatic at-risk siblings demonstrated an IA in almost one-third of cases. Familial SAH/IA segregated with a pattern that was consistent with an autosomal dominant trait in this selected series of sibships, although other factors could produce these findings.

Adult↗
PubMed1995

Cystatin C mutation in an elderly man with sporadic amyloid angiopathy and intracerebral hemorrhage.

BACKGROUND: Cerebral amyloid angiopathy (CAA) with intracerebral hemorrhage (ICH) occurs both sporadically and as a result of mutations in either cystatin C or the amyloid precursor protein. ICH due to cystatin C mutations typically occurs in young people of Icelandic origin. CASE DESCRIPTION: We report a case of sporadic CAA with ICH in an elderly Croatian man with a mutation in cystatin C identical to that found in Icelandic hereditary cerebral hemorrhage with amyloidosis. CONCLUSIONS: This is the first case report of sporadic CAA associated with the same mutation causing hereditary cerebral hemorrhage with amyloidosis of the Icelandic type. Sporadic CAA may thus be associated with genetic mutations in some patients. The frequency of these mutations is yet to be determined.

Cerebral Amyloid Angiopathy↗
PubMed1994

A molecular genetic study of intracerebral hemorrhage.

BACKGROUND: Two forms of inherited intracerebral hemorrhage (ICH) are associated with an amyloid angiopathy caused by mutations in the genes for the amyloid precursor protein or cystatin C. The purpose of this study was to determine whether patients with sporadic ICH have mutations in the amyloid precursor protein or cystatin C genes. METHODS: Consecutive patients with ICH admitted to the neurology or neurosurgery services at Duke University Hospital, Durham, NC, were studied. Using the polymerase chain reaction, we amplified exons 16 and 17 of the amyloid precursor protein and exon 2 of cystatin C and sequenced the products. Twenty-six men and 22 women were studied. The ICH location was deep in 29 patients, lobar in 16, cerebellar in two, and brain stem in one. There were 30 patients (63%) with a positive family history of stroke; seven of them (15%) had a family history of ICH. CONCLUSIONS: Mutations previously reported to cause familial forms of ICH were not found in this group of patients.

Adult↗
PubMed1994

The importance of family history in cerebrovascular disease.

BACKGROUND AND PURPOSE: The role of genetics in cerebrovascular disease remains controversial. The purpose of this study was to assess the influence of family history on atherothrombotic infarction or transient ischemic attack. METHODS: Ninety patients with stroke or transient ischemic attack and 90 age- and sex-matched community control subjects were studied prospectively. Medical and family histories were obtained from all subjects, and a complete physical examination was performed. RESULTS: Eighty-five patients and 86 control subjects knew their family history for ischemic heart disease and stroke. A positive history for ischemic heart disease was present in 62 (73%) of the patients and 46 (53%) of the control subjects (P = .019), and a positive family history for stroke was present in 38 (47%) of the patients and 21 (24%) of the control subjects (P = .014). CONCLUSIONS: Although a positive vascular family history was not an independent risk factor in a multivariate analysis, it was an excellent marker of the presence of other established vascular risk factors. Personal histories of ischemic heart disease, hypertension, and hyperlipidemia were found to be significant independent risk factors for stroke.

Adult↗
PubMedDate not supplied

Familial clustering of intracerebral hemorrhage: a prospective study in North Carolina.

Few studies have assessed the frequency of familial clustering in intracerebral hemorrhage (ICH). Of 144 patients with ICH prospectively assessed, 14 (9.8%) had a positive family history of ICH (FH+). Four pedigrees had more than two affected family members. Comparisons between FH+ and FH- probands demonstrated no significant differences in race, age, sex, ICH type or location. An underlying genetic etiology may account for familial clustering in some ICH patients.

Aged↗