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Differences in medical and surgical therapy for stroke prevention between leading experts in North America and Western Europe.

BACKGROUND AND PURPOSE: Large multicenter trials have evaluated the benefit of different medical and surgical therapies to prevent stroke. However, the application of trial results to clinical practice remains uncertain for some areas of stroke prevention and has been discussed passionately among international experts. As part of a worldwide survey, the purpose of this analysis was to provide an informative and comparative view of the current practice of leading experts in North America (NA) and Western Europe (WE), where most of the large prevention trials have been performed. METHODS: The survey was performed worldwide among 185 neurologists who are currently leading the discussions of stroke prevention practices. It contained questions on the use of antiplatelet agents, oral anticoagulation, and surgery for the prevention of ischemic stroke. The population of this present analysis is the two groups of experts from WE (n=73) and NA (n=48) exclusively. RESULTS: Of each group, >90% responded to the survey. Nearly all respondents reported prescribing aspirin in patients at risk of atherothrombotic stroke, but significant differences between NA and WE are shown by the recommended doses (P<.0001): aspirin doses of >500 mg daily are given exclusively by American participants (36%), whereas doses <200 mg are recommended only in Europe (51%). Eighty-six percent of American versus 59% of European respondents reported using ticlopidine as their second choice (P<.005), and 23% of respondents from WE used warfarin compared with 5% from NA (P<.05). The reported use of anticoagulants in patients with atrial fibrillation increased in accordance with the patient's individual risk of stroke, but respondents from WE were more reluctant to use anticoagulants in patients older than 75 years. Relatively higher target international normalized ratio values were reported by European respondents. Nearly all participants recommend carotid endarterectomy in patients with symptomatic carotid stenosis. The use of carotid endarterectomy in asymptomatic patients was significantly more common among responding experts from NA (48% versus 28%; P<.05), particularly in patients with >95% stenosis (89% versus 53%; P<.0005). CONCLUSIONS: This analysis shows significant differences in several areas of stroke prevention practices between leading experts from NA and WE. These differences may be explained partly by divergent results of trials from the two continents, but in some areas of controversy currently available trial data are not sufficient to form an international consensus to guide daily clinical practice.

Aged↗

André Barbeau and the oculopharyngeal muscular dystrophy in French Canada and North America.

André Barbeau (1931-1986) is best known world-wide in the neurologic community for his contributions to the study of Parkinson's disease, Huntington's chorea and Friedreich's ataxia. But in Québec, Canada, his name is associated with oculopharyngeal muscular dystrophy (OPMD), often called here 'maladie de Barbeau', on which he conducted a series of genealogic, genetic and clinical studies early in his career, most intensively from 1964 to 1966. He then demonstrated that most of the reported cases in North America could be traced back to French-Canadian ancestors. Furthermore, he identified this ancestor couple and linked them with a probable case in Niort, in France. Because he was the first to see over a hundred patients, his clinical studies were definitive. He did little work on OPMD after 1967 when he rushed back to the study of L-DOPA in the treatment of Parkinson's disease, a work that he had previously so brilliantly pioneered.

Family Health↗

Molecular evidence for multiple introductions of garlic mustard (Alliaria petiolata, Brassicaceae) to North America.

Invasive species offer excellent model systems for studying rapid evolutionary change. In this context, molecular markers play an important role because they provide information about pathways of introduction, the amount of genetic variation introduced, and the extent to which founder effects and inbreeding after population bottlenecks may have contributed to evolutionary change. Here, we studied microsatellite variation in eight polymorphic loci among and within 27 native and 26 introduced populations of garlic mustard (Alliaria petiolata), a European herb which is a current serious invader in North American deciduous forests. Overall, introduced populations were genetically less diverse. However, considerable variability was present and when compared to the probable source regions, no bottleneck was evident. Observed heterozygosity was very low and resulted in high inbreeding coefficients, which did not differ significantly between native and introduced populations. Thus, selfing seems to be equally dominant in both ranges. Consequently, there was strong population differentiation in the native (F(ST) = 0.704) and the introduced (F(ST) = 0.789) ranges. The high allelic diversity in the introduced range strongly suggests multiple introductions of Alliaria petiolata to North America. Out of six European regions, the British Isles, northern Europe, and central Europe had significantly higher proportions of alleles, which are common to the introduced range, and are therefore the most probable source regions. The genetic diversity established by multiple introductions, and the lack of inbreeding depression in this highly selfing species, may have contributed to the invasion success of Alliaria petiolata.

Analysis of Variance↗

Genetic characterization of type 2 porcine circovirus (PCV-2) from pigs with postweaning multisystemic wasting syndrome in different geographic regions of North America and development of a differential PCR-restriction fragment length polymorphism assay to detect and differentiate between infections with PCV-1 and PCV-2.

Postweaning multisystemic wasting syndrome (PMWS) is an emerging disease in swine. Increasing evidence indicates that a variant strain of porcine circovirus (PCV), designated type 2 PCV (PCV-2), is responsible for PMWS. To determine the extent of genetic heterogeneity of PCV-2 isolates, the complete genomes of six PCV-2 isolates from different regions of North America were amplified by PCR and sequenced. Sequence and phylogenetic analyses confirmed that two distinct genotypes of PCV exist: nonpathogenic genotype PCV-1 and PMWS-associated genotype PCV-2. However, within the PCV-2 genotype, several minor branches that have been identified appear to be associated with geographic origins. The genomic sequences of two French PCV-2 isolates diverge the most from those of other PCV-2 isolates and form a distinct branch. Other minor but distinguishable branches have also been identified for a Taiwan PCV-2 isolate and two of the Canadian PCV-2 isolates. All the U.S. PCV-2 isolates are closely related, but the Canadian isolates vary, to some extent, in their genomic sequences. The data from this study indicate that although the genome of PCV-2 is generally stable among different isolates, PCV-2 isolates from different geographic regions vary in their genomic sequences. This variation may have important implications for PCV-2 diagnosis and research. On the basis of genetic analyses of available PCV strains, a universal PCR-restriction fragment length polymorphism (PCR-RFLP) assay was developed to detect and differentiate between infections with PCV-1 and PCV-2. This PCR-RFLP assay should be useful for studying the pathogenesis of PCV-2, for detecting PCV-2 infection in pigs from different geographic regions, and for screening donor pigs for use in xenotransplantation.

Amino Acid Sequence↗

Genomic heterogeneity of AIDS retroviral isolates from North America and Zaire.

In an analysis of the genomic variation of AIDS retroviral isolates from patients living in New York, Alabama, and Zaire, restriction maps were constructed by using seven enzymes, each known to cleave the proviral DNA more than once, in conjunction with Southern blot analysis. The maps of LAV, HTLV-III, and ARV-2 as deduced from their published nucleotide sequences were included in this analysis. The results demonstrated that (i) several "signature" restriction sites were common to all isolates; (ii) with the exception of LAV and HTLV-III, the North American and European isolates were all different from one another and showed no geographical specificity; (iii) the African isolates as a group were more diverse than those from North America and Europe; and (iv) the genomic variability was concentrated within the env gene.

Acquired Immunodeficiency Syndrome↗

Two new mechanisms of macrolide resistance in clinical strains of Streptococcus pneumoniae from Eastern Europe and North America.

Resistance to macrolides in pneumococci is generally mediated by methylation of 23S rRNA via erm(B) methylase which can confer a macrolide (M)-, lincosamide (L)-, and streptogramin B (S(B))-resistant (MLS(B)) phenotype or by drug efflux via mef(A) which confers resistance to 14- and 15-membered macrolides only. We studied 20 strains with unusual ML or MS(B) phenotypes which did not harbor erm(B) or mef(A). The strains had been isolated from patients in Eastern Europe and North America from 1992 to 1998. These isolates were found to contain mutations in genes for either 23S rRNA or ribosomal proteins. Three strains from the United States with an ML phenotype, each representing a different clone, were characterized as having an A2059G (Escherichia coli numbering) change in three of the four 23S rRNA alleles. Susceptibility to macrolides and lincosamides decreased as the number of alleles in isogenic strains containing A2059G increased. Sixteen MS(B) strains from Eastern Europe were found to contain a 3-amino-acid substitution ((69)GTG(71) to TPS) in a highly conserved region of the ribosomal protein L4 ((63)KPWRQKGTGRAR(74)). These strains formed several distinct clonal types. The single MS(B) strain from Canada contained a 6-amino-acid L4 insertion ((69)GTGREKGTGRAR), which impacted growth rate and also conferred a 500-fold increase in MIC on the ketolide telithromycin. These macrolide resistance mechanisms from clinical isolates are similar to those recently described for laboratory-derived mutants.

Amino Acid Sequence↗

Phenotypic characteristics of GAD antibody-positive recently diagnosed patients with type 2 diabetes in North America and Europe.

A number of patients with type 2 diabetes are GAD antibody positive. A Diabetes Outcome Progression Trial (ADOPT) is a randomized, double-blind clinical trial in recently diagnosed drug-naive patients with type 2 diabetes that allows for the evaluation of GAD positivity in the context of anthropometric and biochemical characteristics. Of the 4,134 subjects enrolled in ADOPT for whom GAD status was obtained, 174 (4.2%) were GAD positive, with the prevalence of GAD antibodies being similar in North America (4.7%) and Europe (3.7%). Although BMI and age were similar, GAD-positive patients had a lower fasting insulin level, compatible with them being more insulin sensitive. The lower fasting insulin concentration was accompanied by a decreased early insulin response to oral glucose. However, when this insulin response was corrected for the degree of insulin sensitivity, GAD-positive and -negative patients had similar beta-cell function. Consistent with the difference in insulin sensitivity, GAD-positive patients had higher HDL cholesterol and lower triglyceride levels. In the GAD-positive individuals, the prevalence of the metabolic syndrome as defined by NCEP ATP III (National Cholesterol Education Program Adult Treatment Panel III) was also lower (74.1 vs. 83.7%, P = 0.0009). These phenotypic differences may underlie a potential difference in the natural history of hyperglycemia and its clinical outcomes.

Autoantibodies↗

Dental extractions in patients on an oral anticoagulant: a survey of practices in North America.

PURPOSE: The World Health Organization (WHO) recommends the use of the International Normalized Ratio (INR) for reporting prothrombin time (PT) values. However, there are no scientifically based guidelines for performing dental extractions when using the INR. Oral and maxillofacial surgeons were surveyed to determine whether the INR is the method they use to monitor the level of anticoagulation and to determine what protocols are followed when anticoagulated patients require dental extractions. MATERIALS AND METHODS: A mail survey of academic oral and maxillofacial surgeons in North America was conducted to determine their choice of laboratory tests for assessing patients on oral anticoagulants and their protocol before proceeding to dental extractions. RESULTS: Fifty-three of 73 respondents (73%) routinely use the INR, but only 21% rely on this method alone. Twelve percent and 11% of respondents, respectively, also use the PT value and PT ratio. The level of anticoagulation at which surgeons would proceed with dental extractions was variable. For those using the INR, it was from 1.3 to 4.0, for those using PT ratios the perceived safe range was from 1.0 to 2.0, and for those using the PT value, the range was from 13 to 21 sec. CONCLUSIONS: Despite the support in the medical literature for use of the INR, many oral and maxillofacial surgeons still use the PT for monitoring oral anticoagulant therapy. There is no consensus on the INR interval at which dental extractions can be safely performed. Prospective studies are needed in this area.

Administration, Oral↗

Distributions of exotic plants in eastern Asia and North America.

Although some plant traits have been linked to invasion success, the possible effects of regional factors, such as diversity, habitat suitability, and human activity are not well understood. Each of these mechanisms predicts a different pattern of distribution at the regional scale. Thus, where climate and soils are similar, predictions based on regional hypotheses for invasion success can be tested by comparisons of distributions in the source and receiving regions. Here, we analyse the native and alien geographic ranges of all 1567 plant species that have been introduced between eastern Asia and North America or have been introduced to both regions from elsewhere. The results reveal correlations between the spread of exotics and both the native species richness and transportation networks of recipient regions. This suggests that both species interactions and human-aided dispersal influence exotic distributions, although further work on the relative importance of these processes is needed.

Asia↗

Estimates of the distributions of forest ecosystem model inputs for deciduous forests of eastern North America.

Techniques for evaluating uncertainties in process-based, computer simulation models are evolving in response to the proliferation of such models and the demand for their use in the management of forest ecosystems. Many evaluation techniques require precise statements of the uncertainties associated with each model input. Statements of uncertainty are typically formulated as probability density functions (pdfs). Here, pdfs are developed for 29 inputs of the process-based, forest ecosystem, computer simulation model PnET-II, many of which are inputs to other well-known forest ecosystem models. The inputs considered describe vegetation characteristics of forests typical of the Eastern Deciduous Forest biome of North America. Data were compiled largely from published literature to estimate pdfs. The compiled distributions can be used to conduct various model evaluations including uncertainty assessment, calibration, and sensitivity analysis.

Ecosystem↗

Intraspecific variation in the rDNA its loci of 37-collar-spined echinostomes from North America: implications for sequence-based diagnoses and phylogenetics.

The recent finding of the 37-collar-spined Echinostoma revolutum in North America prompted rDNA nucleotide sequence comparisons between this worm and the sympatric Echinostoma trivolvis. Three isolates of E. revolutum from distinct sites and 2 isolates of E. trivolvis collected from a single site were used in this analysis. Sequence data were compared to those from previously sequenced members of the 37-collar-spine group. The 3 North American isolates of E. revolutum were found to be identical, but they differed from Eurasian isolates of E. revolutum at 9 of the 1,006 sites sequenced. Further, 1 of the E. trivolvis isolates studied herein was identical to the published sequence for this species, but 6 nucleotide changes were observed in the second E. trivolvis isolate. Restriction fragment length polymorphisms at this locus support the nucleotide differences found between the E. trivolvis isolates. The degree of intraspecific variation detected raises questions regarding the utility of the internal-transcribed spacer regions of the ribosomal DNA repeat for taxonomic diagnosis and in phylogenetic studies for poorly differentiated groups, such as the 37-collar-spined congeners.

Animals↗

'Babesia gibsoni' of dogs from North America and Asia belong to different species.

18S rDNA sequences from 4 isolates of Babesia gibsoni originating from Japan, Malaysia and Sri Lanka were compared with a previously published, 0.5 kb portion of the 18S rDNA from a B. gibsoni isolate from California, USA, and with the corresponding 18S rDNA sequences of other Babesia spp. Distance, parsimony and maximum likelihood analyses showed almost identical genotypes among the small canine Babesia from Asia, but an unexpectedly distant genetic relationship to that from the USA. While the American isolate segregated together with B. equi, the Asian isolates showed a close relationship to B. divergens and B. odocoilei. These results indicate that small Babesia of dogs originating from North America and Asia belong to different, genetically distantly related species.

Animals↗

Foodborne outbreaks of cyclosporiasis have arisen in North America. Is the United Kingdom at risk?

Cyclospora cayetanensis is a parasitic protozoon that causes prolonged watery diarrhoea. It is endemic in some developing countries, and recent foreign travel is often used as a selection criterion for screening in the United Kingdom (UK). Epidemiological investigations of outbreaks of cyclosporiasis among people in the United States and Canada who had not travelled abroad showed the infection to be foodborne and often associated with foods eaten raw. These included raspberries imported from Guatemala, and pesto (made with basil) and lettuce from other sources. Such foods are also being imported in increasing amounts to the UK, but no outbreaks have been documented, perhaps because none has occurred or because of poor ascertainment. This paper reviews the outbreaks reported from North America, evaluates the risks to the UK population, and suggests how surveillance could be improved.

Animals↗

Leptographium wingfieldii introduced into North America and found associated with exotic Tomicus piniperda and native bark beetles.

Leptographium wingfieldii is a well-known fungal associate of the pine shoot beetle, Tomicus piniperda, in Europe. This fungus is pathogenic to pines and is an important cause of blue-stain in the sapwood of infested trees. Tomicus piniperda was first found in a Christmas tree plantation in Ohio, USA, 1992, but isolation of the fungi associated with these intercepted insects was not attempted. Fungal strains resembling L. wingfieldii were recently isolated from pines attacked by T. piniperda, Dendroctonus valens and Ips pini in the northeastern United States. These strains were morphologically similar to the ex-type and other reference strains of L. wingfieldii. Strains were also compared based on sequences of the partial ITS ribosomal DNA operon, beta-tubulin and elongation factor 1-alpha (EF-1alpha) genes. Based on these DNA sequence comparisons, reference strains of European L. wingfieldii were conspecific with North American strains from pines attacked by T. piniperda, D. valens and I. pini. A single strain from Canada, collected in 1993 near the Ontario border with the USA, shortly after the discovery of T. piniperda in that area and tentatively identified as L. wingfieldii, was also included in this study. Its identification was confirmed, suggesting that L. wingfieldii has been present in this region and probably over the whole range of the insect's distribution for at least a decade. This represents the first record of L. wingfieldii associated with the introduced and damaging pine shoot beetle T. piniperda in North America. It shows that the fungus is well established and can become associated with other native bark beetles that attack stressed and/or dying trees. The occurrence and spread of this highly pathogenic fungus associated with North American bark beetles should be monitored.

Animals↗

Diverse prevalence of large deletions within the OA1 gene in ocular albinism type 1 patients from Europe and North America.

Ocular albinism type 1 (OA1) is an X-linked disorder mainly characterized by congenital nystagmus and photodysphoria, moderate to severe reduction of visual acuity, hypopigmentation of the retina, and the presence of macromelanosomes in the skin and eyes. We have previously isolated the gene for OA1 and characterized its protein product as melanosomal membrane glycoprotein displaying structural and functional features of G protein-coupled receptors. We and others have identified mutations of various types within the OA1 gene in patients with this disorder, including deletions and splice site, frameshift, nonsense, and missense mutations. However, different prevalences of large intragenic deletions have been reported, ranging from 10% to 50% in independent studies. To determine whether these differences might be related to the geographic origin of the OA1 families tested, we performed a further extensive mutation analysis study leading to the identification of pathogenic mutations in 30 unrelated OA1 patients mainly from Europe and North America. These results, together with our earlier mutation reports on OA1, allow us to resolve the apparent discrepancies between previous studies and point to a substantial difference in the frequency of large intragenic deletions in European (<10%) compared with North American (>50%) OA1 families. These observations and our overall refinement of point mutation distribution within the OA1 gene have important implications for the molecular diagnosis of OA1 and for the establishment of any mutation detection program for this disorder.

Albinism, Ocular↗

Recurrent spinal hydatidosis in North America. Case report and review of the literature.

Spinal hydatidosis is an uncommon manifestation of the parasite Echinococcus, affecting fewer than 1% of patients with hydatid disease. The authors report on a 34-year-old Turkish woman who presented with recurrent primary spinal hydatid disease. The patient originally presented with progressive numbness and paraparesis that was reversed after T5-6 laminectomy and cyst removal. Pathological findings indicated parasitic infection and she underwent treatment for cysticercosis. Nevertheless, she returned 4 years later with back pain, numbness, and monoparesis. Neuroimaging studies revealed spinal cord compression with multiple cysts that were again resected. Pathological findings were consistent with Echinococcus. Although this disease is uncommon, particularly in North America, the authors conclude that spinal hydatidosis should be considered in the differential diagnosis of any patient who has lived or traveled within endemic areas and who presents with spine lesions and cord compression. The authors review the literature pertaining to the epidemiological features, presentation, diagnosis, neuroimaging characteristics, recommended treatments, and overall prognosis of spinal hydatidosis.

Adult↗

Rapid Asia-Europe-North America geographic dispersal of earliest Eocene primate Teilhardina during the Paleocene-Eocene Thermal Maximum.

True primates appeared suddenly on all three northern continents during the 100,000-yr-duration Paleocene-Eocene Thermal Maximum at the beginning of the Eocene, approximately 55.5 mya. The simultaneous or nearly simultaneous appearance of euprimates on northern continents has been difficult to understand because the source area, immediate ancestors, and dispersal routes were all unknown. Now, omomyid haplorhine Teilhardina is known on all three continents in association with the carbon isotope excursion marking the Paleocene-Eocene Thermal Maximum. Relative position within the carbon isotope excursion indicates that Asian Teilhardina asiatica is oldest, European Teilhardina belgica is younger, and North American Teilhardina brandti and Teilhardina americana are, successively, youngest. Analysis of morphological characteristics of all four species supports an Asian origin and a westward Asia-to-Europe-to-North America dispersal for Teilhardina. High-resolution isotope stratigraphy indicates that this dispersal happened in an interval of approximately 25,000 yr. Rapid geographic dispersal and morphological character evolution in Teilhardina reported here are consistent with rates observed in other contexts.

Animals↗

Histologic and molecular diagnosis of tularemia: a potential bioterrorism agent endemic to North America.

Francisella tularensis (FT), a zoonotic bacterium that causes tularemia, has received attention as a possible bioterrorism threat. We developed a PCR assay for use in fixed, processed tissues, which are safer to handle and allow archival testing. PCR analysis for a 211-bp fragment of the FT lipoprotein gene was performed on tissues from 16 cases of tularemia. In all, 14/15 cases with intact DNA (93%) were positive for FT by PCR. Frequent histologic findings in PCR-positive tissues included irregular microabscesses and granulomas in liver, spleen, kidney, and lymph nodes, and necrotizing pneumonia. Unusual cases featuring suppurative leptomeningitis and gastrointestinal ulcers were also seen. As this disease is endemic in North America, and has been identified as a potential bioterroristic threat, awareness of the clinicopathologic spectrum of disease and available detection methods is increasingly important. This PCR assay, the first designed for use in processed tissues, is an excellent method for diagnosis of tularemia.

Adolescent↗