bluuebunny/crossref_metadata_2025 huggingface dataset:
Cloning, structural organization, and chromosomal assignment of the porcine c-fos proto-oncogene, FOS
Authors: Reiner G. , Heinricy L. , Brenig B. , Geldermann H. , Dzapo V.
Published: April 2003

The complete porcine c-fos proto-oncogene (FOS) with flanking regions was cloned and sequenced. FOS consists of four exons at amino acids 1–47, 48–131, 132–167, and 168–380 and includes all the typical motifs of the fos proto-oncogene. The promoter contains consensus sequences for CRE, SRE, CaRE, and the E-Box, as well as an AP-1 site. Homologies between human and swine were between 89.7% and 96.3% in the exons. Based on somatic cell hybrid panel screening and known homologies between swine chromosome 7 and human chromosome 14, the porcine c-fos gene was assigned to chromosome 7q23.
DRM/GREMLIN (CKTSF1B1) maps to human chromosome 15 and is highly expressed in adult and fetal brain
Authors: Topol L.Z. , Modi W.S. , Koochekpour S. , Blair D.G.
Published: April 2003

Abstract. We have mapped and characterized the human homolog of Drm/Gremlin (CKTFS1B1), a member of a family of BMP antagonists that have been linked to both developmental and transformation-related functions. By screening a human cDNA library, we isolated a 3.3-kb cDNA containing the 552-bp region encoding the human DRM protein. CKTFS1B1 was localized on human chromosome 15q13→ q15 by somatic cell hybrid analysis and, more precisely, using radiation hybrids, to a region of markers linked to SGNE1, secretory granule neuroendocrine protein 1 and RYR3, the ryanodyne receptor 3. Northern blot analysis showed the presence of a single DRM-specific mRNA expressed in different human tissues, including brain, ovary, intestine and colon. In the brain, DRM expression is associated with the region localized around the internal capsule in the large subcortical nuclei. DRM appears to be predominantly expressed in normal cells and tissues, including normal neurons, astrocytes and fibroblasts. Interestingly, we detected DRM expression in normal cells obtained from several patients, but not in tumor cell lines established from the same patients. The data suggest that down-regulation of DRM is associated with tumor progression, and support the hypothesis that human DRM may play an important role during both neuroembryological development and carcinogenesis.
Comparative cytogenetics of tapirs, genus Tapirus (Perissodactyla, Tapiridae)
Authors: Houck M.L. , Kingswood S.C. , Kumamoto A.T.
Published: April 2003

Chromosomes of the four species of Tapirus were 2n = 52 in T. indicus, 2n = 76 in T. pinchaque, 2n = 80 in T. bairdii, and 2n = 80 in T. terrestris. The number of autosomal arms was 80–94. G-banded karyotypes indicated that a heterochromatic addition/deletion distinguished chromosomes 2 and 3 of T. bairdii and T. pinchaque, respectively. There were at least 13 conserved autosomes between the karyotypes of T. bairdii and T. terrestris, and at least 15 were conserved between T. bairdii and T. pinchaque. In G- and C-banded preparations, the X chromosomes of T. bairdii, T. indicus, and T. terrestris were identical, whereas the X chromosome of T. pinchaque differed from the X of the other species by a heterochromatic addition/deletion. The Y chromosome was a medium-sized to small acrocentric in T. bairdii, T. indicus, and T. pinchaque, but it was not positively identified in T. terrestris. There appeared to be fewer homologies between T. indicus and the three species occurring in Central and South America. Future cytogenetic studies of tapirs from the entire range of each of the four species might provide additional insight into their evolutionary biology and aid wildlife conservation efforts aimed at these threatened mammals.
The genomic structure, chromosome location, and analysis of the human DKK1 head inducer gene as a candidate for holoprosencephaly
Authors: Roessler E. , Du Y. , Glinka A. , Dutra A. , Niehrs C. , Muenke M.
Published: April 2003

Holoprosencephaly (HPE) is the most common developmental defect of the brain and face in humans. Here we report the analysis of the human ortholog of dkk-1 as a candidate gene for HPE. We determined the genomic structure of the human gene DKK1 and mapped it to chromosome 10q11.2. Functional analysis of four missense mutations identified in HPE patients revealed preserved activity in head induction assays in frogs suggesting a limited role for this gene in HPE pathogenesis.
Cloning of the murine Drm gene (Cktsf1b1) and characterization of its oncogene suppressible promoter
Authors: Zhang Q. , Topol L.Z. , Athanasiou M. , Copeland N.G. , Gilbert D.J. , Jenkins N.A. , Blair D.G.
Published: April 2003

The Drm gene, first identified in rat cells in our laboratory, appears to play a significant role in early embryo patterning and limb bud development. We have now isolated mouse Drm (mDrm) cDNA as well as genomic DNA clones and have mapped the Drm gene (Cktsf1b1) to murine chromosome 2. Cktsf1b1 is regulated in a tissue specific fashion and is expressed only in nontransformed mouse cells or primary fibroblasts in culture, but not in established transformed or tumor-derived mouse cell lines. The major transcription start sites map to within 69 bp upstream of the initiating ATG. A promoter was contained in the –214 to +1 bp 5′ flanking region, and promoter/reporter constructs showed 10-fold higher activity than control in REF-1 (rat), A31 (mouse) and CHO (hamster) cells. The region contains a TATA sequence and multiple potential transcription factor binding sites. Promoter activity was dose-dependently inhibited by cotransfection with either ras or mos oncogenes, but oncogene inhibition was reversed and the overall activity increased when cells were treated with the MAP kinase kinase (MKK) inhibitor PD98059. An NF-1 and Yi-like site, identified in the minimal promoter region, showed different mobility shift patterns when normal and transformed cell nuclear extracts are compared. Mutation of the NF-1 site reduced Cktsf1b1 promoter activity 25%, while mutation of the Yi-like site destroyed all the activity. Our results indicate that the expression of Cktsf1b1, a gene associated with early development and cell transformation, is sensitive to MKK levels and may be regulated via multiple transcription factor complexes.
Cloning and characterisation of ITGAV, the genomic sequence for human cell adhesion protein (vitronectin) receptor alpha subunit, CD51
Authors: Sims M.A. , Field S.D. , Barnes M.R. , Shaikh N. , Ellington K. , Murphy K.E. , Spurr N. , Campbell D.A.
Published: April 2003

The integrin family of receptors serves as major receptors for extracellular matrix-mediated cell adhesion and migration, cytoskeletal organisation, cell proliferation, survival, and differentiation. The alpha-V integrins consist of a subset which share a common alpha-V subunit combined with one of five beta subunits (beta-1, 3, 5, 6, or 8). The alpha-V integrins have been implicated in a number of developmental processes, including vasculogenesis and angiogenesis, and are therapeutic targets for inhibition of angiogenesis and osteoporosis. The human cDNA for alpha-V integrin (ITGAV) consists of a 5,717-bp transcript with a coding sequence (CDS) of 3,146 bp encoding a 150-kDa mature peptide. Here we describe the gene structure of ITGAV.
The gene encoding TBC1D1 with homology to the tre-2/USP6 oncogene, BUB2, and cdc16 maps to mouse chromosome 5 and human chromosome 4
Authors: White R.A. , Pasztor L.M. , Richardson P.M. , Zon L.I.
Published: April 2003

TBC1D1 is the founding member of a family of related proteins with homology to t̲re-2/UPS6, b̲UB2, and c̲dc16 and containing the tbc box motif of 180–220 amino acids. This protein family is thought to have a role in differentiation and in regulating cell growth. We set out to map the TBC1D1 gene in mouse and human. Segregation analysis of a TBC1D1 RFLP in two independent mouse RI (recombinant inbred) lines reveals that mouse Tbc1d1 is closely linked to Pgm1 on chromosome 5. The human TBC1D1 gene was assigned to human chromosome 4p15.1→4q21 using Southern blot analyses of genomic DNAs from rodent-human somatic cell lines. A human-specific genomic fragment was observed in the somatic cell lines containing human chromosome 4 or the 4p15.1→4q21 region of the chromosome. TBC1D1 maps to the region containing the ortholog of mouse Pgm1 adding another locus to this long region of conserved synteny between mouse and man.
Thirteen type I loci from HSA4q, HSA6p, HSA7q and HSA12q were comparatively FISH-mapped in four river buffalo and sheep chromosomes
Authors: Di Meo G.P. , Perucatti A. , Schibler L. , Incarnato D. , Ferrara L. , Cribiu E.P. , Iannuzzi L.
Published: April 2003

Thirteen goat BAC clones containing coding sequences from HSA7, HSA12q, HSA4 and HSA6p were fluorescence in situ mapped to river buffalo (Bubalus bubalis, BBU) and sheep (Ovis aries, OAR) R-banded chromosomes. The following type I loci were mapped: BCP to BBU8q32 and OAR4q32, CLCN1 to BBU8q34 and OAR4q34, IGFBP3 to BBU8q24 and OAR4q27, KRT to BBU4q21 and OAR 3q21, IFNG to BBU4q23 and OAR3q23, IGF1 to BBU4q31 and OAR3q31, GNRHR to BBU7q32 and OAR6q32, MTP to BBU7q21 and OAR6q15, PDE6B to BBU7q36 and OAR6q36, BF to BBU2p22 and OAR20q22, EDN1 to BBU2p24 and OAR20q24, GSTA1 to BBU2p22 and OAR20q22, OLADRB (MHC) to BBU2p22 and OAR20q22. All mapped loci appeared to be located on homologous chromosomes and chromosome bands in both bovids. Comparison between gene orders in bovid (BBU and OAR) and human (HSA) chromosomes revealed complex rearrangements, especially between BBU7/OAR6 and HSA4, as well as between BBU2p/OAR20 and HSA6p.
Chromosome mapping of the genes for murine arylamine N-acetyltransferases (NATs), enzymes involved in the metabolism of carcinogens: identification of a novel upstream noncoding exon for murine Nat2
Authors: Fakis G. , Boukouvala S. , Buckle V. , Payton M. , Denning C. , Sim E.
Published: April 2003

Arylamine N-acetyltransferases (NATs) catalyse acetylation reactions which can result in either detoxification or activation of arylamine carcinogens. The human NAT loci (NAT1, NAT2, and a pseudogene, NATP) have been mapped to human chromosome 8p22, a region frequently deleted in tumours. There are three functional genes in mice (Nat1, Nat2, and Nat3) encoding for three NAT isoenzymes. Different alleles at the Nat2 locus are responsible for the acetylation polymorphism identified in different mouse strains. We show that Nat3 is close to Nat1 and Nat2, by screening of a P1 artificial chromosome (PAC) library and provide cytogenetic evidence for co-localisation of the three genes in chromosome region 8 B3.1-B3.3. The Nat region of mouse and human is homologous. We also provide sequence information and a restriction map in the vicinity of Nat1 and Nat2 and describe a noncoding exon located 6 kb upstream of the Nat2 coding region.
Cloning and chromosomal mapping of the mouse and human genes encoding the orphan glucocorticoid-induced receptor (GPR83)
Authors: De Moerlooze L. , Williamson J. , Liners F. , Perret J. , Parmentier M.
Published: April 2003

The mouse glucocorticoid-induced receptor (GIR) is an orphan G protein-coupled receptor highly expressed in brain and thymus (Harrigan et al., 1989; 1991). We have cloned the mouse GIR gene (Gpr83), determined its genomic organization and compared it with the human gene. The genomic organization of the gene is similar in both species although differences leading to specific splicing variants in the mouse have been found. Three introns interrupting the coding sequence are common to both mouse and human. A short sequence in the second intron of the mouse gene can be alternatively spliced in, leading to an insertion in the second intracellular loop of the receptor. This insertion constitutes an addi- tional exon which is not present in the human genome. The human GIR polypeptide shares 89.5% and 91.5% identity with its mouse and dog orthologs respectively. Splice variants lacking the first extracellular loop and the third transmembrane domain have been found in human and mouse species. The receptor variants resulting from these minor transcripts are likely to be non functional. Comparative genetic mapping of the Gpr83 gene showed that it maps to regions of conserved synteny on mouse chromosome 9 (A2–3 region) and human chromosome 11 (q21 region).
Clustering of two fragile sites and seven homeobox genes in human chromosome region 2q31→q32.1
Authors: Limongi M.Z. , Pelliccia F. , Gaddini L. , Rocchi A.
Published: April 2003

In this study we have used FISH to examine the relationship between a group of homeobox genes, namely DLX1/DLX2, EVX2 and four HOXD genes (10, 11, 12, 13), that map to region q31 on chromosome 2, and the FRA2G and FRA2H fragile sites located at 2q31 and 2q32.1 respectively. Our results indicate that these homeobox genes lie between the two fragile regions.
Cloning of leptin cDNA and assignment to the long arm of chromosome 5 in the marsupial Sminthopsis crassicaudata
Authors: Hope P.J. , Webb G.C. , Lok S. , Hope R.M. , Turnbull H. , Jelmberg A.C. , Wittert G.A.
Published: April 2003

We have isolated and sequenced full-length cDNA clones for leptin in the dasyurid marsupial Sminthopsis crassicaudata (fat-tailed dunnart). Southern and in situ hybridisation data indicated a single leptin gene in the S. crassicauda- ta genome, localised to arbitrary chromosome bands 5q24→ q31 on the long arm of chromosome 5, the short-arm terminus of which bears the only nucleolar organising region. The nucleotide sequence of the cDNAs revealed that the primary translation product of S. crassicaudata leptin is composed of 167 amino acid residues, with a potential signal peptide of 21 residues. The mature protein of 146 amino acids is 82% similar to both the mouse and human proteins and is predicted to have a molecular weight of 16.26 kDa. Northern blot analysis revealed that the corresponding mRNA is approximately 3.9 kb in size and is expressed only in white adipose tissue of this marsupial species. Evolutionary analyses indicate that S. crassicaudata leptin cDNA has evolved at a significantly faster rate than cDNAs from eutherian mammals.
Functional Outcome in Stroke Inpatient Rehabilitation: Predicting No, Low and High Response Patients
Authors: Paolucci Stefano , Antonucci Gabriella , Pratesi Luca , Traballesi Marco , Lubich Sergio , Grasso Maria Grazia
Published: April 2003

The aims of this study were: (1) to identify reliable prognostic factors for detecting subgroups of no, low and high response in consecutive patients admitted for rehabilitation of first stroke sequelae, and (2) to quantify the relative risk of poor or excellent prognosis on both Activities of Daily Living (ADL) and mobility for each significant variable. We prospectively studied 440 of 475 patients. From a group of 32 independent variables, those significantly associated with no, low and high effectiveness on both ADL and mobility were selected by means of multiple regression; then, the relative risk was calculated for each variable that significantly entered the multiple regressions. Patients with severe impairment or with global aphasia showed a relative risk of no response 4–6 times higher than that of other patients. An interval before rehabilitation longer than 2 months was associated with an increasing risk of no response. Elderly patients had a significantly higher relative risk of low response both on ADL and mobility. The presence of hemineglect and depression was associated with an increasing risk of low response on ADL but not on mobility. The absence of hemineglect and a short interval are prerequisites for an excellent functional prognosis on both ADL and mobility. A minor impairment, employed status, the absence of global aphasia and age ≤65 years increased the risk of high response. At the beginning of treatment, clear prognostic factors for the detection of subgroups with poor or excellent rehabilitation prognosis can be identified.
Internal Borderzone Infarction in Patients with Ischemic Stroke
Authors: Gandolfo Carlo , Del Sette Massimo , Finocchi Cinzia , Calautti Cinzia , Loeb Carlo
Published: April 2003

Objective: The mechanism underlying cerebral infarction in the borderzone between the territories of deep and superficial perforating arteries has not yet been clarified. This study was performed to investigate the prevalence, volume, site, and etiology of this type of subcortical infarction in a large unselected group of stroke patients. Methods and Patients: We analyzed a continuous series of 383 patients with recent cerebral infarction observed in our Stroke Unit. Patients underwent a complete clinical and instrumental workup. The subgroup of subjects with internal borderzone infarct alone were compared with the subgroups of patients with other types of cerebral infarcts by uni- and multivariate statistical tests. Results: There were 90 internal borderzone infarcts of 725 ischemic lesions (12% of the total), with a median volume of 0.32 ml (95% confidence interval 0.24–0.44; range: 0.012–20.2 ml). Internal borderzone infarcts alone occurred in only 13 of 383 (3.4%) patients. A comparison between patients with ‘pure’ internal borderzone infarction and patients with other types of cerebral infarcts by multiple logistic regression analysis demonstrated a significant independent causal role of carotid stenosis or occlusion. Conclusion: Our study suggests that ‘pure’ internal borderzone infarctions are quite rare findings in patients with ischemic stroke, and that the hemodynamic impairment due to atherosclerotic occlusion or stenosis of the carotid system could be the cause in the large majority of cases.
Correlates of Dependent Living3 Months after Ischemic Stroke
Authors: Pohjasvaara Tarja , Erkinjuntti Timo , Vataja Risto , Kaste Markku
Published: April 2003

To examine the correlates of dependent living after ischemic stroke, a consecutive cohort of 486 patients aged 55–85 years was examined 3 months after the index stroke. Detailed medical, neurological and radiological stroke evaluation, structured measures of cognition, emotion and behavior, activities of daily living (ADL), physical disability, and assessment of dependent living were performed. Independent correlates of dependent living 3 months after stroke were the presence of the major hemispheral stroke syndrome (odds ratio, OR, 11.8, 95% confidence interval, CI, 7.2–19.9), and a combination of handicap (Rankin Scale, OR 3.9, 95% CI 2.6–6.1), cognition (DSM-III-R dementia, OR 3.9, CI 1.5–10.7; any cognitive decline, OR 4.5, CI 2.0–11.2), and ADL [Functional Activities Questionnaire (FAQ), OR 1.2, 95% CI 1.1–1.2]. The Rankin Scale explained 51.5%, FAQ 5.9% and presence of DSM-III-R dementia or any cognitive decline 3.4% of the total variance between dependent and independent patients after stroke. Independent of the effects of physical disability, presence of cognitive impairment has important functional consequences on stroke patients. Our findings emphasize the importance of the evaluation of cognitive functions in both observational and interventional clinical trials, as well as in treatment planning, rehabilitation and guidance of patients with ischemic stroke.
Heparin Treatment in Acute Cerebral Sinus Venous Thrombosis: A Retrospective Clinical and MR Analysis of 42 Cases
Authors: Brucker A.B. , Vollert-Rogenhofer H. , Wagner M. , Stieglbauer K. , Felber S. , Trenkler J. , Deisenhammer E. , Aichner F.
Published: April 2003

The only randomized data on heparin treatment in acute cerebral sinus venous thrombosis (CSVT) are derived from a small number of patients. The rate of intracranial hemorrhages as a complication of high-dose heparin treatment is still unknown. This retrospective study evaluates the clinical features, neuroimaging monitoring and outcome of 42 patients with proven CSVT. Diagnosis was established by DSA, CT, MR tomography and MR angiography. All patients received heparin intravenously guided by doubling the aPTT value for 3 weeks, followed by oral anticoagulation. Partial or complete recanalization was found in 36 cases. 40 patients improved clinically, in 26 of them complete recovery was observed. One patient deteriorated and developed an apallic syndrome, one further patient died of septic multiorgan failure. Only in one patient was hemorrhagic transformation of infarcted brain tissue observed but without clinical deterioration.
Significance of Carotid Restenosis following Endarterectomy
Authors: Ganesan R. , Cote R. , Mackey A.
Published: April 2003

Background and Purpose: The clinical significance of restenosis after carotid endarterectomy as detected by duplex ultrasound has not been clearly established. To address this problem, we retrospectively evaluated the experience at two university-affiliated hospitals. Methods: All charts of patients with carotid endarterectomies between June 1987 and April 1995 were reviewed. Inclusion required neurological assessment and postoperative duplex ultrasound. Exclusion was based on a known source of cardioembolic disease, or recent (<6 months) myocardial infarction. Primary clinical endpoints were ipsilateral transient ischemic attack (TIA) or ischemic stroke. Contributing vascular risk factors were also identified. The effect of restenosis on event-free survival was analyzed using life tables and Gehan-Wilcoxon rank sum tet. Logistic regression was used to identify independent risk factors for restenosis and vascular events. Results: One hundred and eighty-seven patients were identified who underwent a total of 207 endarterectomies. Mean follow-up was 30.4 ± 20.9 months during which a total of 64 vascular events, including 42 TIAs, 18 strokes, and 4 vascular deaths occurred. Of these 21 TIAs and 8 strokes were ipsilateral to the side of endarterectomy. Event rates were compared for patients with ipsilateral high- (≥50%) and low-grade (<50%) restenosis. These two groups were comparable in terms of baseline risk factors. There was no significant difference in vascular event rates (for either ipsilateral events or events in any vascular territory) between the group with high- and low-grade restenosis. Nor was any such difference in event rates shown for patients who showed ipsilateral progression of carotid disease on serial ultrasound. However, patients operated for symptomatic carotid disease had a significantly higher risk of neurological events (p = 0.035). Logistic regression failed to disclose any other risk factors that were independently predictive of either restenosis or vascular events during follow-up. Conclusion: This study does not show a difference in vascular event rates for higher grades of carotid restenosis after carotid endarterectomy. Routine surveillance with carotid ultrasound does not appear to identify patients at higher risk for postoperative cerebrovascular events.
Impact of Carotid Endarterectomy upon Cognitive Functioning
Authors: Lunn Sarah , Crawley Francesca , Harrison Michael J.G. , Brown Martin M. , Newman Stanton P.
Published: April 2003

Background and Purpose: The extent to which carotid endarterectomy (CEA) influences cognitive functioning has been the subject of a number of studies often with conflicting conclusions. This paper systematically reviews the literature in an attempt to clarify this issue. Results: Although the majority of studies (16/28) reported an improvement in cognition after surgery, a substantial minority (12/28) found no change. Studies before 1984 tended to report an improvement, while later studies tended to report no change in cognition. Cognitive improvement was also more likely the longer the time interval between CEA and assessment. The studies were found to differ on many methodological factors, e.g. sample size, type of patient and control group, severity and side of carotid stenosis, the range of cognitive tests and timing of postoperative assessment. Conclusion: Given the conflicting findings, and the methodological issues, it is not possible to draw a clear conclusion regarding the impact of carotid endarterectomy upon cognition. Future research which pays attention to these methodological factors is needed in order to adequately resolve the current debate.
Neuropsychological Features of Dementia due to Dural Arteriovenous Malformation
Authors: Jaillard Assia Serradj , Peres Blandine , Hommel Marc
Published: April 2003

We report two patients aged 65 and 61 years, who presented a subacute dementia with normal CT scan without contrast injection. Angiography showed a dural arteriovenous malformation. The patients improved dramatically with treatment of the malformation. Dementia was characterised by frontal dysfunction, emotional disorders, mnesic and praxic impairment. This neuropsychological pattern suggests a profile of global dementia in the field of vascular dementia.
Age-Related Transcranial Doppler Findings in the Evaluation of Cerebral Circulation during Postprandial and Postural Tests
Authors: Poli Leone , Bo Mario , Secreto Piero , Zanocchi Mauro , Bottino Piero
Published: April 2003

We used transcranial Doppler (TCD) to investigate whether there are cerebral circulation differences between young and elderly subjects in response to postprandial postural changes. Preprandial and postprandial systolic and diastolic blood pressure, heart rate, mean middle cerebral artery (MCA) velocity (Vmean MCA), systolic/diastolic MCA velocity ratio (Vs/Vd MCA) and pulsatility index (PI) were determined in 15 healthy elderly subjects (mean age 74.3 ± 6.5 years) and in 10 younger subjects (mean age 31.6 ± 7.2 years) in the supine position and after a postural change. As compared with young subjects, elderly ones showed a greater postprandial systolic pressure decline (p < 0.05) associated with a significant decrease of Vmean MCA (p < 0.05), and a greater increase of Vs/Vd and PI (p < 0.05 both). We conclude that, as compared with young subjects, elderly ones have reduced cerebrovascular adaptive response to pressure modifications induced by postprandial postural changes.
Cerebrovascular Response to Dynamic Changes in pCO2
Authors: Garnham J. , Panerai R.B. , Naylor A.R. , Evans D.H.
Published: April 2003

Fifty-six subjects with carotid artery disease were assessed by measuring the cerebral blood flow velocity (CBFV) change in response to inhalation of 5% CO2 in air whilst continuously monitoring the blood pressure (BP). Coherent averaging of the data characterised differences in CBFV, BP, resistance area product and critical closing pressure during changes in end-tidal CO2 (ETCO2). The results primarily demonstrate that the augmentation of ETCO2 increases the CBFV and BP, causing a pressure autoregulatory response, and allows the processes of pressure autoregulation and cerebral vascular reserve to be differentiated.
Prospective Study on the Complication Rate of Carotid Surgery
Authors: Hartmann Andreas , Hupp Thomas , Koch Hans-Christian , Dollinger Peter , Stapf Christian , Schmidt Regina , Hofmeister Christoph , Thompson JohnL.P. , Marx Peter , Mast Henning
Published: April 2003

Background: Randomized trials of carotid endarterectomy for high-grade stenosis have shown a benefit for surgery under the condition of low perioperative complication rates. Concerns have been expressed that the complication rates of carotid surgery are higher in everyday practice and may vary considerably between centers. We prospectively established the complication rate for carotid surgery in a single institution. Design: Prospective 2-year study. All patients received pre- and postoperative neurological evaluation. Laboratory tests included pre- and postoperative brain imaging, intracranial and neck vessel sonography, conventional angiography, magnetic resonance angiography, and intraoperative monitoring. Participants: 108 consecutive patients: 54 symptomatic patients fulfilling the inclusion criteria of the European Carotid Surgery Trial (ECST) and 54 asymptomatic patients fulfilling the inclusion criteria of the North American Trial on Asymptomatic Stenoses (ACAS). Setting: Single academic center with a high volume of carotid endarterectomies (>50 per year). Participating center in ECST. Main Outcome Measures: Stroke or death as defined in the randomized trials. Results: The overall complication rate was 8.3% (95% CI 4.1–15.6%). Complications were more frequent in patients with symptomatic stenosis (11.1%, CI 4.6–23.3%) than in asymptomatic cases (5.6%, CI 1.5–16.4%). Three patients died (2 strokes, 1 myocardial infarction). Disabling strokes were found in 2 patients (Rankin scale scores 3 and 4). Nondisabling strokes (Rankin scale score 1 and 2) occurred in 4 patients. The complication rates for symptomatic and asymptomatic patients were higher than the ones reported in the randomized trials, but 95% confidence intervals showed that the differences were not statistically significant. The point estimates of complication rates still supported a benefit of surgery for patients with symptomatic stenosis, but denied a positive effect of endarterectomy for patients with asymptomatic stenosis. Conclusion: In this center, a beneficial effect of carotid surgery for asymptomatic stenoses cannot be safely assumed.
Carotid and Vertebral Artery Injury following Severe Head or Cervical Spine Trauma
Authors: Rommel Oliver , Niedeggen Andreas , Tegenthoff Martin , Kiwitt Paul , Bötel Uwe , Malin Jean-Pierre
Published: April 2003

In order to determine the frequency of neck vessel injuries, Doppler investigations were performed in 60 patients following either severe head injury (n = 29), cervical spine injury (n = 26), or combined head and cervical spine injury (n = 5). The majority of patients were referred to our hospital for early rehabilitation; before admission Doppler investigations had been performed in only 2 patients. Clinically, 3 patients sustained severe cerebral ischemia due to neck vessel trauma: 1 patient with left-sided ICA dissection after head trauma revealed Doppler abnormalities only in the early phase of the disease; the second patient demonstrated persistent Doppler abnormalities due to traumatic right-sided ICA and VA occlusion. The third patient sustained a fatal vertebral and basilar artery thrombosis following cervical spine injury. In 57 patients without clinical signs suspicious of neck vessel trauma, sonography revealed abnormali- ties in 3 patients (11%) with severe head injury and in 6 patients (20%) with cervical spine or combined head and spine injury, in both groups mainly related to the vertebrobasilar system. Neck vessel injury is probably an underdiagnosed complication of severe head or cervical spine trauma. Although interpretation of Doppler findings may be difficult, particularly in the vertebrobasilar system, Doppler investigations can be recommended as a screening method to exclude neck vessel injuries.
What is the Cost of Admitting Patients with Transient Ischaemic Attacks to Hospital?
Authors: Gubitz Gordon , Phillips Stephen , Dwyer Victoria
Published: April 2003

Financial constraints at our institution prompted us to evaluate the management of patients referred to the Acute Stroke Service because of transient ischaemic attack (TIA). We analysed age, gender, length of stay, hospital costs, discharge disposition and stroke recurrence for all cases of TIA admitted to the Acute Stroke Service between January 1, 1994, and December 31, 1996. During this time, 110 cases of TIA were admitted. All had a CT head scan, 60% had carotid Doppler ultrasound, and 30% had transthoracic echocardiography. No patients admitted with TIA died, and 92% were discharged home. The average annual cost of in-patient management of TIA was 328,000 Canadian dollars, of which 95% were accounted for by the cost of the hospital bed alone. If hospitalisation of patients with TIA could be reduced, significant cost-savings could be realised.
Endovascular Treatment of Carotid Dissecting Aneurysms
Authors: Butterworth Richard J. , Thomas Dafydd J. , Wolfe John H.N. , Mansfield Averil O. , Al-Kutoubi Aghiad
Published: April 2003

Background and Purpose: Cervical arterial dissection is a well-recognised cause for acute ischaemic stroke. Dissecting aneurysms commonly occur in the affected vessels contributing to the clinical presentation. Persistence of these aneurysms may provide a source of future embolic events as well as causing local symptoms or even be at risk of spontaneous rupture. Methods: We describe 4 patients with traumatic internal carotid artery (ICA) dissections with aneurysm formation at the skull base. Three of the 4 patients still had carotid aneurysms on follow-up investigations and so underwent endovascular procedures using stenting and coil techniques. The carotid aneurysm resolved spontaneously in the fourth patient. Results: The endovascular procedures resulted in significant reduction or obliteration of the flow within the carotid aneurysms with restoration of the true lumen diameter in the adjacent ICA in all 3 patients. No perioperative complications were experienced except for transient headache in 2 patients. Conclusions: In patients with persistent aneurysms the exact risk of subsequent ischaemic events remains unknown and prospective long-term studies are needed to ascertain this risk. If recurrent stroke rates are found to be high, then carotid stenting (with or without coil insertion) is a feasible invasive approach which could be considered in these patients.
Interrater Reliability of the National Institutes of Health Stroke Scale: Rating by Neurologistsand N urses in a Community-Based Stroke Incidence Study
Authors: Dewey Helen M. , Donnan Geoffrey A. , Freeman Elspeth J. , Sharples Catherine M. , Macdonell Richard A.L. , McNeil John J. , Thrift Amanda G.
Published: April 2003

The reliability of the National Institutes of Health Stroke Scale (NIHSS) for use by trained neurologists in clinical trials of acute stroke has been established in several hospital-based studies. However, it also has the potential for application in community-based settings and to be used by nonneurologists: issues which have not been explored before. Hence, we aimed to determine the reliability of the NIHSS when administered by research nurses within the existing North Eastern Melbourne Stroke Incidence Study. Using the NIHSS, thirty-one consecutively registered stroke patients were assessed by 2 neurologists and 1 of 2 trained research nurses. The interrater reliability of observations was compared using weighted and unweighted kappa statistics and intraclass correlation coefficients (ICC). There was a high level of agreement for total scores between the 2 neurologists (ICC = 0.95) and between each neurologist and research nurse (ICC = 0.92 and 0.96). While there was moderate to excellent agreement among neurologists and research nurse (weighted κ > 0.4) for the majority of the NIHSS items, there was poor agreement for the component ‘limb ataxia’. Overall, agreement between nurse and neurologist for individual items was not significantly different from agreement between neurologists. It appears that in both hospital and community settings, trained research nurses can administer the NIHSS with a reliability similar to stroke-trained neurologists. This ability could be used to advantage in large community-based trials and epidemiological studies.
Presentation and Prognosis of Bilateral Infarcts in the Territory of the Superior Cerebellar Artery
Authors: Stangel Martin , Stapf Christian , Marx Peter
Published: April 2003

Unilateral cerebellar infarcts in the territory of the superior cerebellar artery (SCA) have been studied in recent years to delineate the clinical presentation and stroke mechanism, but most studies excluded bilateral infarctions. We have studied patients with bilateral SCA infarctions to provide data on clinical findings, stroke distribution and outcome. We collected data of 8 patients with bilateral SCA infarctions recognized by computed tomography and/or magnetic resonance imaging. The most common clinical presentation of patients with bilateral SCA infarctions were nausea, vomiting or vertigo (6 patients), often associated with ataxia and dysarthria (5 patients). Further symptoms were variable and depended on additional infarcts in other vascular territories. Infarcts were often partial or scattered with equal distribution between the medial and lateral branches of the SCA. Complete infarction within the SCA area occurred in less than half of the cases. Clinical outcome was either benign (full recovery in 3 patients) or fatal (5 patients). Predictors for a good clinical recovery were young age, few vascular risk factors, only partial involvement of the SCA territory without involvement of other vascular territories, and absent limb weakness on clinical presentation.
The Dose-Response Relationship of Acetazolamide on the Cerebral Blood Flow in Normal Subjects
Authors: Grossmann Werner M. , Koeberle Bernhard
Published: April 2003

Background: Acetazolamide (AA) is used to determine the cerebral vasoreactivity (CVR). To investigate whether the usually applied standard dose of 1 g intravenously will guarantee stable test conditions, the dose-response relationship of AA on cerebral blood flow (CBF) and cerebral blood flow velocity (CBFV) in normal subjects was determined. Methods: In 59 healthy volunteers, rCBF was measured with a 133Xenon inhalation device, and CBFV of the middle cerebral artery (MCA) by transcranial Doppler sonography. The first CBF measurement was taken at rest, the second 15 min after application of AA at a dosage of 5, 10, 13, 15 and 18 mg/kg of body weight, respectively. The CBFV (n = 52) of the middle cerebral artery on the side of the better temporal window was taken 25 min after application of AA 13 mg/kg. In order to determine the side effects of AA, statements of an additional 172 patients were included. Results: A significant dosage dependence of AA on the CBF (fast flow and initial slope index) exists between 5 and 18 mg/kg intravenously. After AA 13 mg/kg, the fast flow increases from 70.8 ± 10.8 to 110.1 ± 13.5 ml/100 g/min, the initial slope index from 46.5 ± 5.4 to 62.8 ± 5.8, and the CBFV from 51.5 ± 8.5 to 85.4 ± 14.2 cm/s. The CVR of CBF and CBFV ascertained that way shows an age dependence equivalent to the situation at rest. Severity and frequency of side effects are dosage-dependent, significantly in part, but reversible without exception. Conclusion: For the determination of CVR of CBF with AA, a dosage related to body weight is required. The usually applied standard dose of 1 g intravenously is not sufficient for standardized test conditions. For evaluation of the results obtained, the apparent age dependence of CVR must be taken into account. Because of the severity of side effects occurring at a higher dose, an AA dosage of 13 mg/kg intravenously is recommended.
Correlates of Informant-Rated Cognitive Decline after Stroke
Authors: Starr John M. , Nicolson Catherine , Anderson Kathryn , Dennis Martin S. , Deary Ian J.
Published: April 2003

Cognitive impairment is common after stroke, but measurement is problematic. Six tests of mental ability, unaffected by loss of limb function, were administered to 49 subjects of mean age 74.2 years at a median of 4.3 years (range 0.1–16.8) after stroke together with a depression score and the IQCODE, an informant-rated scale of estimated cognitive decline. Over 90% of stroke patients were able to complete most tests. IQCODE correlated significantly with the HADS depression score (r = 0.35, p = 0.040), the 2-year Barthel score (r = –0.60, p = 0.001) and with a general cognitive factor extracted from the mental ability test scores (r = –0.42, p = 0.016). We conclude that informant-rated methods offer a promising approach to measuring cognitive decline after stroke.
Cerebral Venous Infarction following Thrombosis of the Draining Vein of a Venous Angioma (Developmental Abnormality)
Authors: Masson C. , Godefroy O. , Leclerc X. , Colombani J.M. , Leys D.
Published: April 2003

We report two cases of cerebral venous angioma presenting as venous infarction, one in the left parietal lobe, the other in the left frontal lobe. Cerebral imaging demonstrated thrombotic occlusion of the draining vein of the venous angioma associated in the latter case with thrombosis of the anterior part of the superior longitudinal sinus. Both patients were free of coagulopathy. They were treated with anticoagulant therapy. One completely recovered, while the other was left with slight residual disability. Thrombosis of the draining vein has been reported in only 6 previous cases, of whom only 2 received anticoagulant therapy. Discovery of a venous angioma in the diagnostic workup of a patient with recent neurological disorders should raise the question of a possible occlusion of the draining vein and lead to an appropriate therapy.
Management of Resistant Hypertension in Patients with Carotid Stenosis: High Prevalence of Renovascular Hypertension
Authors: Spence J. David
Published: April 2003

Introduction: Patients with carotid stenosis are at high risk of vascular events and therefore require an optimal control of risk factors such as hypertension. As the treatment of hypertension differs according to the cause, we examined the prevalence of resistant hypertension, and the cause of hypertension, among patients with carotid stenosis followed closely in two randomized trials of carotid endarterectomy. Objective: The purpose of this study was to determine the prevalence of resistant hypertension and of secondary hypertension among patients with carotid stenosis. Methods: A chart review was performed of all patients from our center who participated in the North American Symptomatic Carotid Endarterectomy Trial or the Asymptomatic Carotid Artery Study to determine the prevalence of renovascular hypertension. Results: Among 170 patients with carotid stenosis followed in these two trials, 145 (83.5%) were hypertensive (systolic >160 or diastolic >90 mm Hg); at least 24 (14.1% overall, 16.6% of hypertensives) had renovascular hypertension based on either nuclear medicine renography, renal angiography or both; among the 79 patients with resistant hypertension (mean arterial pressure >130 mm Hg despite treatment), 20 (25.3%) had renovascular hypertension. Adrenocortical hyperplasia was the underlying cause of hypertension in 12 (7.1% of cases, 8.3% of hypertensives, 8.8% of resistant hypertensives). Blood pressures were significantly higher for patients with renovascular and adrenocortical hypertension (p < 0.0001 for systolic, p = 0.024 for diastolic pressures). Conclusion: Among patients with carotid stenosis, renovascular hypertension is unusually common. Resistant hypertension among such patients should lead to investigation and management directed at the cause of hypertension. Appropriate investigations might include plasma renin/aldosterone ratio, captopril renography and MRA of the renal arteries or renal angiography.
Role of a Stroke Data Bank in Evaluating Cerebral Infarction Subtypes: Patterns and Outcome of 1,776 Consecutive Patients from the Besançon Stroke Registry
Authors: Moulin Thierry , Tatu Laurent , Vuillier Fabrice , Berger Eric , Chavot Didier , Rumbach Lucien
Published: April 2003

The purpose of this study was to estimate the frequency of various risk factors, courses and outcome of infarct subtypes in a large hospital-based stroke registry. Methods: From 1987 to 1994, 1,776 stroke patients with a first-ever infarction were included in the Besançon Stroke Registry. All patients were evaluated by a standard protocol (risk factors, stroke onset, stroke courses, clinical characteristics, neuroimaging, Doppler ultrasonography and cardiac investigations). Outcome was evaluated at 30 days using the Rankin scale. Results: There were 1,012 men (mean age 67.2 ± 13.7 years) and 764 women (mean age 71.4 ± 15.6 years). At least two neuroimaging examinations were performed in 81.4% (n = 1,446) of the patients and an infarct was visible in 80.9% (n = 1,436). The second neuroimaging examination (CT or MRI) was performed after 8.2 ± 1.6 days. 85.4% of patients were admitted on the first day of the stroke: 28.3% within 3 h and 48.4% within 6 h. In addition, stroke severity was well correlated with the short time interval between stroke onset and admission. Past medical history of hypertension was the major risk factor occurring in 57.5% of all types of infarction. While diabetes was more frequently found in small deep infarct, atrial fibrillation and history of heart failure were found in anterior circulation infarcts. The distribution of clinical presentations was conventional. Hemorrhagic transformation was found in 14.9% of the patients, especially in MCA and PCA infarcts. In all patients, logistic regression analysis determined independent predictive factors for death: clinical deterioration at the 48th hour (OR 7.5, 95% CI 4.9–11.3), initial loss of consciousness (OR 3.3, 95% CI 2.1–4.9), age (OR 1.05, 95% CI 1.03–1.06), complete motor deficit (OR 2.6, 95% CI 1.7–3.8), history of heart failure (OR 1.9, 95% CI 1.3–3.0), lacunar syndrome (OR 0.25, 95% CI 0.10–0.60) and regressive stroke onset (OR 0.24, 95% CI 0.10–0.52). However, the outcome was clearly correlated with the infarct location. The in-hospital mortality rate was lowest in patients with small deep infarct (2.9%) or border zone infarcts (3.4%) and the highest in patients with total middle cerebral artery infarct (47.4%) or multiple infarcts (27.6%). Conclusion: Our registry appears to be a useful tool to understand the course and outcome of a large group of nonselected patients with subtypes of infarction. It can also help to analyze the influence of specific stroke management in the different categories of stroke types.
Stroke as the First Manifestation of Calcific Aortic Stenosis
Authors: Oliveira-Filho Jamary , Massaro Ayrton R. , Yamamoto Fábio , Bustamante Luiz , Scaff Milberto
Published: April 2003

Heart valve calcifications are rarely recognized as a potential source for cerebral embolism. Previous studies have identified mitral, but not aortic, valve calcifications to be risk factors for stroke. Based on these studies, heart surgery is unlikely to be indicated in patients who present with a stroke and an ‘incidental’ aortic valve calcification. We report a case of a 46-year-old man presenting with acute onset of left-sided weakness and numbness. A previous smoking history was the only cardiovascular risk factor found. Head CT scan revealed a right middle cerebral artery territory infarct and an adjacent high-density lesion. CT angiography demonstrated the presence of calcific embolic material in the middle cerebral artery. A search for embolic sources revealed a calcific aortic stenosis (CAS). Initially placed on coumadin, the patient developed silent myocardial infarction 2 months later, presumed to be also embolic in origin from the CAS. After aortic valve replacement, the patient has been symptom-free during a 2-year follow-up. In conclusion, CT angiography may be the method of choice for detecting calcific cerebral emboli, and demonstration of a causal relationship between CAS and an embolic stroke by CT angiography may be an important adjunct in surgical decision-making.