Homocysteine, MTHFR 677C-->T polymorphism, and risk of ischemic stroke: results of a meta-analysis.

BACKGROUND: Data are conflicting concerning risk for ischemic stroke associated with hyperhomocyst(e)inemia (hyper-Hcy) and a common polymorphism in the gene encoding 5,10-methylenetetrahydrofolate reductase (MTHFR 677C-->T), which predisposes to hyper-Hcy in vivo. METHODS: Search of MEDLINE, Science Citation Index, and abstracts of conference proceedings revealed relevant articles. Exposure was defined as follows: 1) prevalence of hyper-Hcy; 2) absolute difference in the mean Hcy concentration between subjects with and without ischemic stroke; and 3) the MTHFR TT genotype frequency. Outcome was defined as ischemic stroke with or without neuroimaging. Inclusion criteria were retrospective and prospective studies with reported odds ratios (OR) or hazard ratios (HR) or arithmetic mean Hcy levels. Exclusion criteria were absence of OR or HR, outcome defined as carotid atherosclerosis or intima-media thickening, stroke in patients younger than 18 years old, and studies in languages other than English. Statistical analyses for between-study heterogeneity and pooled risk estimates were performed using Stata software (Stata Corporation, College Station, TX). RESULTS: Among 16 studies (1,487 stroke and 2,554 nonstroke cases), the pooled mean Hcy level in patients with ischemic stoke was 2.32 micromol/L (95% CI, 1.6 to 3.04; p < 0.001) greater than that in those without ischemic stroke. Among 14 included studies (1,769 stroke and 7,400 nonstroke cases), the pooled OR estimate of ischemic stroke associated with hyper-Hcy was 1.79 (95% CI, 1.61 to 2.0; p < 0.001). Among 19 included studies (2,788 stroke and 3,962 nonstroke cases), the OR associated with the TT genotype was 1.23 (95% CI, 0.96 to 1.58; p = 0.1). CONCLUSION: These data support an association between mild-to-moderate hyper-Hcy and ischemic stoke. The MTHFR TT genotype may have a small influence in determining susceptibility to ischemic stoke.

Preoperative imaging of the carotid bifurcation. Current trends.

BACKGROUND: There is disagreement about the most appropriate imaging examination necessary for the preoperative assessment of the carotid bifurcation. Our objective was to find out the preferences of clinicians on this issue in one large hospital. And to determine whether and how these preferences have changed over time. STUDY DESIGN: Observational, retrospective study. SETTING: Large metropolitan and university affiliated hospital. Numbers of patients per year who underwent carotid endarterectomy during 1990-1998. Numbers of patients per year who had conventional catheter carotid angiography during the same period. Assessment of the nature of preoperative carotid imaging in a sample of 400 patients (100 each in 1990, 1993, 1996 and 1998). Analysis of the types of imaging examinations by year and determination of underlying trends. MEASURES: Number of carotid angiograms expressed as a percentage of carotid endarterectomies performed each year. Types of preoperative imaging examinations of the carotids and changes over time. RESULTS: The number of preoperative conventional catheter angiograms decreased over time. In 1990 angiography was performed in 86% of carotid endarterectomies. In 1998 the proportion decreased to 16% (p<0.05). Conversely, the proportion of endarterectomies carried out based solely on ultrasonography increased from 6% in 1990 to 56% in 1998 (p<0.05). The proportion of endarterectomies performed based on the combined findings of ultrasound and magnetic resonance angiography increased from 3% in 1990 to 56% in 1996 and to 26% in 1998. Computed tomoangiography has not become popular. The observed reduction in the number of preoperative conventional carotid angiograms was independent of the presence/absence of symptoms, the level of serum creatinine, the subspecialty of the surgeon (vascular surgery vs neurosurgery) and the individual surgeon involved. CONCLUSIONS: In one large university affiliated hospital the trend in the preoperative imaging of the carotid arteries is moving away from conventional catheter angiography. There is increasing application of ultrasound combined with magnetic resonance angiography and a more pronounced trend towards the performance of carotid endarterectomy based only on ultrasonography.

Molecular characterization of a murine, major A/B type hnRNP protein: mBx.

We have previously identified a discrete hnRNP polypeptide of the A/B type, named mBx, as an abundant protein species in murine cells. The molecular characterization of this protein is now accomplished. From all evidence provided, mBx polypeptide represents a new gene product, distinct from the known members of the A/B family A1 and A2/B1. It is, instead, mostly related to a still hypothetical human protein of A/B type, as well as to the Xenopus hnRNPA3 protein species.

Aetiology of fever in patients with acute stroke.

OBJECTIVE: Fever in patients with acute stroke is usually related to infectious complications. In some cases, a focus of infection cannot be identified, fever does not respond to empirical antibiotic treatment and is thought to be due to the central nervous system lesion. The aim of this study was to determine the frequency and origin of fever in patients with acute stroke and the characteristics associated with the presence of fever. DESIGN: A retrospective study of 36 months' duration. SETTING: The study was carried out at 'Alexandra' Hospital, a tertiary care teaching centre in Athens, Greece. SUBJECTS: A total of 330 patients hospitalized for acute stroke from June 1992 until July 1994. RESULTS: In 37.6% of 330 patients, fever was noted; 22.7% had a documented infection and 14.8% had fever without a documented infection. In univariate analysis, older age was associated with the presence of fever (P = 0.001). The development of fever was associated with intracerebral haemorrhage versus ischaemic infarct (P < 0.001) and with the presence of mass effect (P < 0.001), transtentorial herniation (P < 0.001), intraventricular blood (P < 0. 001), and larger size of ischaemic infarct (P = 0.0001) and of haemorrhage (P = 0.0002). Patients with fever had lower scores on admission on the Glasgow Coma Scale (P = 0.0001) and the Scandinavian Stroke Scale (P = 0.0001). The development of fever was associated with prior use of an invasive technique (P < 0.001) and more specifically with urinary catheterization (P < 0.001), but not with the presence of risk factors for infection. Patients with fever had a worse outcome assessed by the Modified Rankin Scale (P = 0. 0001) and the Barthel Index (P = 0.0001). In multivariate analysis, age, Scandinavian Stroke Scale score and mass effect were found to be significantly associated with fever (P = 0.035, P = 0.0001 and P = 0.0004, respectively). Patients with fever without documented infection had an earlier onset of fever than those with infection (P = 0.0061). In a logistic regression analysis, the only factor predictive of fever without documented infection versus infection was earlier onset of fever (P = 0.029). CONCLUSION: Patients with acute stroke who develop fever are older, suffer severe stroke, their fever is associated with the use of invasive techniques, and they have a poor outcome. In patients with fever without a focus of infection, the only characteristic that is different from patients with known infection is earlier onset of fever.

Recognition of subsets of the mammalian A/B-type core heterogeneous nuclear ribonucleoprotein polypeptides by novel autoantibodies.

The structurally related A/B-type core heterogeneous nuclear ribonucleoprotein (hnRNP) polypeptides of 34-39 kDa (A1, A2, B1 and B2) belong to a family of RNA-binding proteins that are major components of 40 S hnRNP complexes. By two-dimensional gel electrophoresis and peptide mapping analysis we compared each member of the A/B-type core proteins in the human and rat liver cells. This comparison revealed the unique presence in rat cells of major protein species, referred to as mBx polypeptides, that appeared as three charge isoforms at a position corresponding to the minor HeLa B1b protein spot. In addition, clear differences in the ratios of the A1 polypeptide to the A1b isoform were observed. The detection, in sera of patients with rheumatic autoimmune diseases, of two novel autoantibody specificities, one recognizing solely B2 protein and the second both the B2 and mBx polypeptides, helped to identify mBx proteins as new A/B-type hnRNP components, immunologically related to B2 protein. A common immunoreactive V8 protease peptide of approx. 17 kDa has been identified in B2 and mBx hnRNP polypeptides. mBx protein species are identified in cells of murine origin, and have a ubiquitous tissue distribution and developmental appearance.