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Biomedical subjects

M J Alberts

Publications and source records attributed to M J Alberts.

At least 19 recordsLinked to original sources
PubMed2001

Advances in the genetics of cerebrovascular disease and stroke.

MEDLINE searches identified epidemiologic, experimental, and clinical studies on the genetics of cerebrovascular disease and stroke, including the following topics: genetic epidemiology of stroke; genetics of systemic disorders that cause ischemic stroke, including coagulation disorders, connective tissue disorders, vasculopathies, metabolic disorders, and disorders of unknown etiology; and genetics of systemic disorders that cause hemorrhagic stroke. Recent discoveries in stroke genetics involve the genetic basis of monogenic disorders such as cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy and sickle cell disease. Reproducing similar advances in other forms of cerebrovascular disease and stroke will be more difficult because their inheritance is complex, multigenic, and heterogeneous. However, the future is promising with the application of molecular genetic approaches such as linkage analysis, allele-sharing methods, association studies, and polygenic analysis of experimental crosses as well as the transmission/disequilibrium test--a statistical method for detection of linkage between a marker and a disease-susceptibility locus.

Cerebral Hemorrhage↗
PubMed2001

Suppression of recurrent transient ischemic attacks by a statin agent.

Recent studies of hydroxy-methylglutaryl coenzyme A reductase inhibitors have demonstrated that therapy with statins is associated with a significant decrease in the risk of stroke and TIA in patients with coronary artery disease. The underlying mechanism responsible for this effect is unclear. The author presents two patients who had cessation of TIAs upon institution of statin therapy. A variety of non-lipid-lowering mechanisms may account for this beneficial effect. This initial observation, if confirmed by further study, may suggest a role for statin agents in preventing recurrent TIAs.

Aged↗
PubMed2001

Use of exponential diffusion imaging to determine the age of ischemic infarcts.

OBJECTIVE: Diffusion-weighted magnetic resonance imaging (DWI) detects acute ischemic infarcts with high lesion conspicuity. Determination of infarct age is difficult on DWI alone because infarct signal intensity (SIinfarct) on DWI is influenced by T2 properties ("T2 shine-through"). Maps of the apparent diffusion coefficient (ADC) reflect pure diffusion characteristics without T2 effects but have low lesion conspicuity. Thus, in clinical practice, combined use of DWI and ADC maps is required. Exponential DWI (eDWI) is an innovative means of MRI-diffusion data analysis that merges the advantages of DWI and ADC maps. The authors hypothesized that SIinfarct on eDWI would correlate with infarct age. The authors studied 114 consecutive patients who had 120 ischemic strokes with clearly determined onset times and who underwent echo-planar DWI. The eDWI were generated by dividing the signal intensity on DWI by that on the corresponding T2 image on a pixel-by-pixel basis. SIinfarct on eDWI was measured in the lesion core and expressed as a percentage of contralateral control tissue. On eDWI, relative SIinfarct changed significantly with infarct age (P < .0001). When patients were sorted in infarct-age groups, no significant differences were found within the first 120 hours. However, for patients studied within 5 days, the mean relative SIinfarct was significantly higher compared with patients studied > or = 8 days after stroke (P < .05). For all infarcts up to 5 days old, the eDWI signal intensity was higher than control tissue (hyperintense appearance). All infarcts > 10 days old had an eDWI signal intensity lower than control tissue (hypointense appearance). The authors concluded that the use of eDWI, as a single set of images, reliably differentiates acute infarcts (< or = 5 days old) from infarcts > 10 days old. This feature would be expected to be helpful when the distinction between acute and nonacute infarction cannot be determined on clinical grounds.

Adolescent↗
PubMed2000

Recommendations for the establishment of primary stroke centers. Brain Attack Coalition.

OBJECTIVE: To develop recommendations for the establishment and operation of primary stroke centers as an approach to improve the medical care of patients with stroke. PARTICIPANTS: Members of the Brain Attack Coalition (BAC), a multidisciplinary group of representatives from major professional organizations involved with delivering stroke care. Supplemental input was obtained from other experts involved in acute stroke care. EVIDENCE: A review of literature published from 1966 to March 2000 was performed using MEDLINE. More than 600 English-language articles that had evidence from randomized clinical trials, meta-analyses, care guidelines, or other appropriate methods supporting specific care recommendations for patients with acute stroke that could be incorporated into a stroke center model were selected. CONSENSUS PROCESS: Articles were reviewed initially by 1 author (M.J.A.). Members of the BAC reviewed each recommendation in the context of current practice parameters, with special attention to improving the delivery of care to patients with acute stroke, cost-effectiveness, and logistical issues related to the establishment of primary stroke centers. Consensus was reached among all BAC participants before an element was added to the list of recommendations. CONCLUSIONS: Randomized clinical trials and observational studies suggest that several elements of a stroke center would improve patient care and outcomes. Key elements of primary stroke centers include acute stroke teams, stroke units, written care protocols, and an integrated emergency response system. Important support services include availability and interpretation of computed tomography scans 24 hours everyday and rapid laboratory testing. Administrative support, strong leadership, and continuing education are also important elements for stroke centers. Adoption of these recommendations may increase the use of appropriate diagnostic and therapeutic modalities and reduce peristroke complications. The establishment of primary stroke centers has the potential to improve the care of patients with stroke. JAMA. 2000.

Clinical Protocols↗
PubMed1999

Intracerebral hemorrhage outcome: apolipoprotein E genotype, hematoma, and edema volumes.

We investigated whether early hematoma or edema volumes could explain the adverse association between APOE epsilon4 and survival in intracerebral hemorrhage. Among 102 patients, epsilon4 carriers had a higher mortality rate than non-epsilon4 carriers (38 versus 24%, p = 0.05). Nonsurvivors had larger hematoma (75.5 cm3 versus 27.1 cm3, p<0.001) and edema volumes (37.5 cm3 versus 17.1 cm3, p<0.01), but these were not associated with epsilon4 after adjusting for race, age, and type of hemorrhage.

Aged↗
PubMed1999

APOE genotype as a risk factor for ischemic cerebrovascular disease: a meta-analysis.

OBJECTIVE: To determine whether a specific apolipoprotein E (APOE) polymorphism is a risk factor for ischemic cerebrovascular disease (CVD; stroke or TIA). BACKGROUND: The APOE epsilon4 allele is overrepresented in AD, atherosclerosis, and ischemic heart disease. In addition, epsilon4 carriers have higher plasma cholesterol levels than non-epsilon4 carriers. METHODS: Using Medline (OVID and PubMed), a search was performed for all studies that examined APOE in ischemic CVD. The authors identified nine case-control studies that were suitable for analysis. RESULTS: There were 926 patients with ischemic stroke or TIAs and 890 age- and sex-matched control subjects. Overall analysis revealed a significantly higher APOE-epsilon4 allelic frequency in affected patients compared with control subjects (0.14 versus 0.09; odds ratio, 1.68; 95% CI, 1.36 to 2.09; p<0.001). There was a significant excess of the epsilon3 allele (0.85 versus 0.80) but not the epsilon2 allele (0.06 versus 0.06) in the control subjects compared with the ischemic CVD patients. Seven studies had data on APOE genotypes. Carriers of epsilon4 were more frequent among ischemic CVD patients than control subjects (27% versus 18%; odds ratio, 1.73; 95% CI, 1.34 to 2.23; p<0.001). CONCLUSIONS: The APOE-epsilon4 allele and carriers of epsilon4 are more frequent among patients with ischemic CVD compared with control subjects. The epsilon2 allele does not appear to be protective for ischemic CVD. These findings imply a role for the APOE genotype in the pathogenesis of some cases of ischemic CVD.

Alleles↗
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↗
PubMed1999

Diagnosis and treatment of ischemic stroke.

Most patients who have a stroke are evaluated initially by a primary care physician. For patients to benefit from new stroke therapies that must be initiated within a few hours of stroke onset, primary care physicians must be prepared to diagnose stroke and initiate acute treatment. This article provides information on the rapid and accurate diagnosis and management of patients with acute ischemic stroke. This information is particularly relevant due to the relatively high risk:benefit ratio associated with some acute stroke therapies, such as tissue plasminogen activator. Information is also provided about medical and surgical therapies to prevent subsequent strokes.

Anticoagulants↗
PubMed1999

Cerebral amyloid angiopathy-related hemorrhage. Interaction of APOE epsilon2 with putative clinical risk factors.

BACKGROUND AND PURPOSE: Current evidence suggests that the apolipoprotein E (APOE for gene; apoE for protein) epsilon4 allele predisposes to cerebral amyloid angiopathy (CAA) whereas epsilon2 is associated with CAA-related hemorrhage (CAAH). The clinical risk factors for other forms of intracranial hemorrhage are a less-frequent feature of CAAH. In this study we examined potential clinical risk factors in patients with CAAH and assessed these with respect to APOE genotype. METHODS: Thirty-six patients were identified with a pathological diagnosis of CAAH. Clinical notes were reviewed to document age of hemorrhage onset, history of dementia, antiplatelet/anticoagulant medication, hypertension, minor head trauma, or transient neurological events. In a review of reported cases of CAAH, the frequency of these clinical features was also recorded. APOE genotypes were determined with use of polymerase chain reaction techniques. RESULTS: There were 24 women and 12 men; the mean age was 70.3 years. One third (n=12) had been taking antiplatelet medication, and a similar number were demented. Nine patients were hypertensive, and 4 had a history of recent minor head trauma. The relative frequency of each of these clinical features was similar to that in previous reports. Forty-four percent (16 of 36) possessed an epsilon2 allele. Antiplatelet or anticoagulant medication, hypertension, or minor head trauma were significantly more frequent antecedents of CAAH in epsilon2 carriers than in non-epsilon2 carriers (81% versus 35%, P=0.008), antiplatelet/anticoagulant medication in particular (P=0.038). CONCLUSIONS: Our findings suggest that antiplatelet or anticoagulant medication, hypertension, or minor head trauma are most likely to precipitate cerebral hemorrhage in patients with CAA who are also epsilon2 carriers. This may result from isoform-specific effects of apoE on the structure of amyloid-laden blood vessel walls.

Aged↗
PubMed1998

Acute hemodynamic changes during carotid artery stenting.

To determine the clinical significance of acute hemodynamic disturbances during stenting in the carotid sinus region, we assessed the relation between intraprocedural changes in heart rate (HR) and blood pressure (BP) and adverse neurologic and cardiac outcomes. Eighteen patients underwent carotid stenting with the Wallstent (Schneider Inc). Suitable candidates had at least 60% diameter stenosis of the carotid artery by angiography. Initial and nadir HR and BP were recorded during the predilatation, stent delivery, and postdilatation periods. Bradycardia was defined as HR < or =60 beats/min and hypotension as systolic BP < or =100 mm Hg. Nineteen Wallstents were successfully deployed in all 19 carotid arteries. Some degree of bradycardia or hypotension occurred in 68% of carotid stent procedures, but administration of vasoactive medications was necessary in only 7 patients (37%) with more persistent hemodynamic disturbances. Hypotension or the need for continuous vasopressor therapy was significantly more common during postdilatation (32%) than in the predilatation period (5%) (p = 0.02). Bradycardia was not reduced by prophylactic atropine. In 1 patient the hemodynamic response to stenting may have contributed to an adverse neurologic and cardiac outcome. Thus, despite frequent fluctuations in HR and BP, most carotid stenting procedures were performed with excellent overall results, even in patients at high risk.

Aged↗
PubMed1998

Acute stroke teams: results of a national survey. National Acute Stroke Team Group.

BACKGROUND AND PURPOSE: The sensitivity of the brain to brief periods of profound ischemia or prolonged periods of modest ischemia mandates an aggressive approach to acute stroke care. Past studies have shown that many stroke patients do not receive acute care in an urgent and timely fashion. The formation of acute stroke teams (AST) is one approach that can be used to accelerate the delivery of acute stroke care. METHODS: We conducted a survey of major stroke program directors and neurovascular experts throughout the United States. The survey focused on issues related to the presence of AST, their staffing, operational features, and utilization at the surveyed programs and hospitals. RESULTS: Surveys were returned from 45 of 60 centers. Ninety-one percent of the respondents indicated that they currently had an AST, with 66% formed between 1995 and 1997. Staffing of ASTs consisted of attending physicians (95%), nurses or study coordinators (73%), fellows (49%), and residents (46%). In almost all cases (98%), the AST was led by a neurologist or neurosurgeon, and 98% of the ASTs operated on a 24-hours-per-day, 7-days-per-week basis. The most common call frequency was 2 to 3 times per week (41%), followed by >5 calls per week (29%). In 59% of the cases, the teams cost </=$5000 per year to operate. The vast majority (78%) of ASTs responded within 10 minutes of receiving a call. CONCLUSIONS: The formation of ASTs is quite common at the surveyed programs. Although staffing patterns vary, most teams are led by neurologists or neurosurgeons. The utilization of ASTs varies by facility, but they appear to be useful, with only a modest incremental financial cost. The use of ASTs may assist in providing more rapid medical care to stroke patients and increase the use of some acute therapies. Extension of the AST concept to nonacademic hospitals appears feasible.

Academic Medical Centers↗
PubMed1998

tPA in acute ischemic stroke: United States experience and issues for the future.

The approval of tissue plasminogen activator (tPA) for treatment of patients with ischemic stroke in the United States marked the first therapy proven to reverse or limit the effects of an acute stroke. Despite this approval and the lack of an alternative therapy, the use of tPA in stroke has been quite low. Several explanations for this underutilization have been identified, including lack of patient awareness, potential complications, infrastructure deficiencies, and physician concerns. This article explores these issues and suggests strategies for improving the use of tPA as an acute therapy in stroke.

Acute Disease↗
PubMed1997

Hyperacute stroke therapy with tissue plasminogen activator.

The past year has seen tremendous progress in developing new therapies aimed at reversing the effects of acute stroke. Thrombolytic therapy with various agents has been extensively studied in stroke patients for the past 7 years. Tissue plasminogen activator (t-PA) received formal US Food and Drug Administration approval in June 1996 for use in patients within 3 hours of onset of an ischemic stroke. Treatment with t-PA improves neurologic outcome and functional disability to such a degree that, for every 100 stroke patients treated with t-PA, an additional 11-13 will be normal or nearly normal 3 months after their stroke. The downside of t-PA therapy is a 6% rate of symptomatic intracerebral hemorrhage (ICH) and a 3% rate of fatal ICH. Studies are under way to determine whether t-PA can be administered with an acceptable margin of safety within 5 hours of stroke, to evaluate the therapeutic benefits of intraarterial pro-urokinase, and to assess the use of magnetic resonance spectroscopy to identify which patients are most likely to benefit from thrombolysis. Combination thrombolytic-neuroprotectant therapy is also being studied. In theory, patients could be given an initial dose of a neuroprotectant by paramedics and receive thrombolytic therapy in the hospital. We are now entering an era of proactive, not reactive, stroke therapies. These treatments may reverse some or all acute stroke symptoms and improve functional outcomes.

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↗