bluuebunny/crossref_metadata_2025 huggingface dataset:
Construction of a whole-genome radiation hybrid panel for high-resolution gene mapping in pigs
Authors: Yerle M. , Pinton P. , Robic A. , Alfonso A. , Palvadeau Y. , Delcros C. , Hawken R. , Alexander L. , Beattie C. , Schook L. , Milan D. , Gellin J.
Published: April 2003

We have developed a panel of 152 whole-genome radiation hybrids by fusing irradiated diploid pig lymphocytes or fibroblasts with recipient hamster permanent cells. The number and size of the porcine chromosome fragments retained in each hybrid clone were checked by fluorescence in situ hybridization with a SINE probe or by primed in situ labeling (PRINS) with SINE-specific primers. A strategy based on the interspersed repetitive sequence polymerase chain reaction (IRS-PCR) was developed for selected clones to determine if the large fragments painted by the SINE probe corresponded to one pig chromosome or to different fragments of several chromosomes. This strategy was buttressed by a double PRINS approach using primers specific for α-satellite sequences of two different groups of swine chromosomes. Genome retention frequency was estimated for each clone by PCR with 32 markers localized on different porcine chromosomes. Of the 152 hybrids produced, 126 were selected on the basis of cytogenetic content and chromosome retention frequency to construct a radiation hybrid map of swine chromosome 8. Our initial results for this chromosome indicate that the resolution of the radiation hybrid map is 18 times higher than that obtained by linkage analysis.
Analysis of genetic heterogeneity among five gynogenetic clones of silver crucian carp, Carassius auratus gibelio Bloch, based on detection of RAPD molecular markers
Authors: Zhou L. , Wang Y. , Gui J.F.
Published: April 2003

The gynogenetic silver crucian carp, Carassius auratus gibelio, is a unique model system for studying evolutionary genetics and selective breeding, owing to its specific genetic background and reproductive modes. Five gynogenetic clones were analyzed by the random amplified polymorphic DNA (RAPD) technique, using 30 10-nucleotide-long primers. Twenty-six primers produced well-amplified DNA fragments with reproducible banding patterns, and 24 primers were polymorphic. Nearly identical banding patterns were observed among individuals within each clone, suggesting that each clone might possess a specific pattern owing to its gynogenesis. In contrast, the RAPD patterns of the five clones differed from each other. A phylogenetic tree was constructed using UPGMA cluster analysis based on a total of 3,744 distinguishable fragments (156 per individual). Average genetic distances within and among the five clones clearly indicated their intraclonal homogeneity, interclonal heterogeneity, and phylogenetic relationships. Clones A and P were the most closely related, whereas the most divergence was seen between clone D and clone E or F. A total of 88 polymorphic fragments were scored from 24 primers after excluding bands that were monomorphic for the five clones. Most primers corresponding to the polymorphic fragments amplified reproducible markers specific for one clone or that were shared by two, three, or four clones. Several primers (e.g., Opj-1, Opj-7, and Opp-10) produced abundant banding patterns that could be used to discriminate between the five clones. Markers specific for one or two clones were also identified. The RAPD markers identified in this study will likely benefit evolutionary genetics and selective breeding studies.
Human secretin (SCT): gene structure, chromosome location, and distribution of mRNA
Authors: Whitmore T.E. , Holloway J.L. , Lofton-Day C.E. , Maurer M.F. , Chen L. , Quinton T.J. , Vincent J.B. , Scherer S.W. , Lok S.
Published: April 2003

Secretin is an endocrine hormone that stimulates the secretion of bicarbonate-rich pancreatic fluids. Recently, it has been discussed that secretin deficiency may be implicated in autistic syndrome, suggesting that the hormone could have a neuroendocrine function in addition to its role in digestion. In the present study, the human secretin gene (SCT) was isolated from a bacterial artificial chromosome genomic library. SCT contains four exons, with the protein coding regions spanning 713 bp of genomic DNA. Human SCT is similar structurally to the secretin genes of other species. Amino acid conservation, however, is most pronounced within the exon encoding the biologically active mature peptide. Northern blot analysis shows that human SCT transcripts are located in the spleen, intestinal tract, and brain. Radiation hybrid mapping places the SCT locus on chromosome 11p15.5.
Safety and Tolerability of 619C89 after Acute Stroke
Authors: Muir Keith W. , Hamilton Steven J.C. , Lunnon Martin W. , Hobbiger Stephen , Lees Kennedy R.
Published: April 2003

Background: 619C89 is a use-dependent sodium channel blocker which reduces hemispheric infarction volume by up to 60% after permanent middle cerebral artery occlusion in rats. Intravenous doses of up to 1 mg/kg have been well tolerated by healthy young and elderly volunteers. This study sought to assess safety and tolerability of 619C89 in the treatment of acute stroke. Methods: Patients were randomised within 12 h of onset of stroke to receive 619C89 or placebo as an intravenous loading dose, followed by maintenance doses given 8 hourly for 64 h in a double-blind, ascending-dose tolerance study. Dosing commenced at 0.5 mg/kg loading plus 0.25 mg/kg/8 h maintenance for the first group and increased in increments of 0.5 mg/kg loading +0.25 mg/kg/8 h maintenance thereafter. Safety evaluation was continued for 3 months. Results: 48 patients were recruited. 12 received placebo and 36 received 619C89 in doses up to 2.5 mg/kg loading plus 1.25 mg/kg/8 h. Dose escalation was stopped after the occurrence of hallucinations in 5 of 18 patients who received 2 mg/kg +1 mg/kg/8 h or more. Gastro-intestinal upset and confusion were also possibly drug related. No drug-related effects on cardiovascular function were found. Conclusions: 619C89 was associated with significant central nervous system side-effects at doses of 2 mg/kg +1 mg/kg/8 h or greater as discrete intravenous infusions within 12 h of stroke onset. It may also cause gastro-intestinal side-effects. Doses below this are well tolerated in patients. No adverse cardiovascular effects were seen.
Alpha-1-Antitrypsin Deficiency in Spontaneous Intracranial Arterial Dissections
Authors: Schievink Wouter I. , Katzmann Jerry A. , Piepgras David G.
Published: April 2003

α1-Antitrypsin deficiency has been associated with a variety of vascular disorders including arterial aneurysms, spontaneous extracranial arterial dissections, and arterial fibromuscular dysplasia. We determined the distribution of α1-antitrypsin phenotypes in patients with intracranial arterial dissections, a rare cause of subarachnoid hemorrhage. The study population consisted of 4 consecutive patients with subarachnoid hemorrhage due to spontaneous intracranial arterial dissections. The vertebral artery was involved in 3 patients and the posterior inferior cerebellar artery in 1 patient. Three of these 4 patients were found to have a heterozygous α1-antitrypsin deficiency (PiMZ or PiMS phenotypes). These data support previous studies suggesting that patients with α1-antitrypsin deficiency may be at an increased risk of developing spontaneous arterial dissections.
Mitochondrial DNA in Stroke and Migraine with Aura
Authors: Ojaimi Joseline , Katsabanis Sophie , Bower Simon , Quigley Anita , Byrne Edward
Published: April 2003

Patients presenting with thrombotic stroke of unexplained etiology and or migraine with aura were screened for mitochondrial (mt) DNA mutations associated with cytopathies given that both migraine and stroke-like episodes are recognised with certain mt DNA mutations. Mutations usually associated with either mitochondrial encephalopathy, lactic acidosis and stroke-like episode, myoclonic epilepsy with ragged red fibres, or those strongly linked to Leber’s hereditary optic neuropathy (LHON) were not detected in patients or controls. However, increased levels of two of the secondary LHON mutations were found. The T→C mutation at nucleotide 4216 was more common than expected in patients aged 35 years or less, as was the 13708 G→A mutation in young stroke patients. This data lends support to the possibility that an accumulation of minor mt DNA mutations may contribute to the pathoaetiology of stroke and migraine with aura in some young patients.
Poststroke Atrial Fibrillation Bursts with Sinus Rhythm at Stroke Onset: What Was the Cause of Stroke?
Authors: Vuilleumier Patrik , Bogousslavsky Julien , Henriques Isabel , Kappenberger Lukas
Published: April 2003

Intermittent atrial fibrillation may cause stroke, and acute stroke may lead to secondary bursts of atrial fibrillation. We studied with continuous ECG before, during and after stroke a patient with a history of intermittent atrial fibrillation. To our knowledge, this is the first case with continuous monitoring of atrial fibrillation bursts and their precise timing in the peristroke period.
Pathophysiological Assessment of Nitric Oxide (Given as Sodium Nitroprusside) in Acute Ischaemic Stroke
Authors: Butterworth R.J. , Cluckie A. , Jackson S.H.D. , Buxton-Thomas M. , Bath P.M.W.
Published: April 2003

Acute ischaemic stroke is characterised by reductions in local cerebral blood flow (CBF) and activation of circulating platelets and leucocytes. Nitric oxide is a vasodilator and can inhibit these circulating cells. The aim of this study was to assess the effect of nitric oxide on platelet function and regional CBF in patients with acute ischaemic stroke. Sodium nitroprusside (SNP), a spontaneous nitric oxide donor, was administered at a dose which caused a 10 mm Hg fall in mean arterial blood pressure (MABP) in a pathophysiological study to 22 patients with acute ischaemic stroke and 12 matched control subjects. Platelet function (whole blood aggregation and flow cytometry) was assessed before and during SNP administration. Changes in regional CBF were measured using single photon emission computerised tomography (SPECT) scanning. SNP significantly reduced platelet aggregation in both the patient and control subject groups. Equally, the expression of platelet adhesion molecules P-selectin (CD62) and glycoprotein (GP) GP IIIa (CD61) were significantly reduced in both groups. GP Ia (CDw49b) expression was significantly attenuated in the patient but not in the control group. Four patients underwent SPECT scanning and improvements in local CBF corresponding to the penumbral area of the clinical stroke site were seen in 3 of these patients. A total of 24 regions of asymmetrical perfusion were examined, pre-SNP (median (SQR)), 0.68 (0.14) vs. peri-SNP 0.78 (0.17), 2p = 0.065. SNP, given at a dose which reduced MABP by 10 mm Hg, significantly inhibited platelet aggregation and adhesion molecule expression. Improved regional CBF was seen in some patients. SNP is a candidate therapeutic agent for patients with acute ischaemic stroke and warrants further study.
Warfarin, Aspirin and Microembolic Signals in the Acute Phase of Stroke in a Patient with Mechanical Heart Valves
Authors: Del Sette Massimo , Angeli Silvia , Gandolfo Carlo
Published: April 2003

We report the case of a 54-year-old woman, with atrial fibrillation and mechanical heart valves, who suffered a left-hemispheric stroke while she was under warfarin. Daily bilateral simultaneous transcranial Doppler monitoring of the middle cerebral arteries showed the presence of microembolic signals (MES), whose number remained unchanged after adding aspirin 100 mg daily. We conclude that anticoagulant plus antiplatelet therapy does not influence the number of MES in the acute phase of stroke in patients with prosthetic heart valves, suggesting the gaseous origin of MES in these patients.
Intracerebral Haemorrhage in AIDS
Authors: Roquer Jaume , Palomeras Ernest , Knobel Hernando , Pou Adolf
Published: April 2003

We report 8 patients with the acquired immunodeficiency syndrome (AIDS) and intracerebral haemorrhage. There were 7 men and 1 woman (mean age 37.2 years) with a mean CD4 count of 81.2/mm3. Alcohol abuse was recorded in 7 patients, intravenous drug use in 4, homosexual activity in 2, thrombocytopaenia in 1 and severe hypertension in 1. There were 5 lobar and 3 deep haemorrhages. Potential aetiologies of intracerebral haemorrhage included cerebral toxoplasmosis (n = 2), thrombocytopenia (n = 2), hypertension (n = 1) and cerebral tuberculosis (n = 1). Data of these patients were compared with those of 30 AIDS inpatients without brain haemorrhage matched by age and sex and no statistically significant differences in risk factors for AIDS except for alcohol abuse (>80 g/day) (p = 0.045) were found. Causes of brain haemorrhage in AIDS patients are heterogeneous. The relationship between both conditions may be explained by the effect of several predisposing factors to stroke in association with AIDS-related complications. Intracerebral haemorrhage is a late and serious complication of AIDS (mortality 62.5%). The frequency of intracerebral haemorrhage in AIDS (1.0%) is higher than that expected in a general population of young adults.
Cardiovascular Safety of Lubeluzole (Prosynap®) in Patients with Ischemic Stroke
Authors: Hacke W. , Lees K.R. , Timmerhuis T. , Haan J. , Hantson L. , Hennerici M. , Diener H.C.
Published: April 2003

The cardiovascular safety of lubeluzole was evaluated in patients with ischemic stroke in a double-blind, placebo-controlled trial. Forty-six patients were randomized to receive a continuous daily infusion of lubeluzole 5 mg (loading dose 3.75 mg over 1 h), lubeluzole 10 mg (loading dose 7.5 mg over 1 h), or placebo for 5 days within 24 h of stroke onset. The primary measure of cardiovascular safety was the QTc interval, derived from the continuous electrocardiogram (ECG) and measured during treatment and a 2-day follow-up. Compared with placebo, neither dosage of lubeluzole had any statistically or clinically relevant effects on the QTc. Neither were there any significant differences among the three treatment groups in the area under the curve for heart rate, QT interval, QT dispersion, or QTlc. Lubeluzole did not increase the frequency of ECG abnormalities. No ventricular fibrillation, ventricular tachycardia, or torsades de pointes were observed in any of the treatment groups. During this trial, 3 patients in the placebo group and 2 patients in the lubeluzole 5-mg group died. There were no deaths in the lubeluzole 10-mg group. Adverse experiences were similar in all three treatment groups except that superficial thrombophlebitis was more frequent in the lubeluzole 10-mg group. In doses to 10 mg/day, lubeluzole has a favorable cardiovascular safety profile, as demonstrated by the lack of clinically relevant effects on heart rate, QT, QTc, and QTlc, and it was well tolerated by patients with ischemic stroke.
Functional Recovery and Social Outcome after Cerebral Infarction in Young Adults
Authors: Neau Jean-Philippe , Ingrand Pierre , Mouille-Brachet Claire , Rosier Marie-Pierre , Couderq Christine , Alvarez Arturo , Gil Roger
Published: April 2003

This study was designed to assess the return to work, the poststroke depression and the quality of life after a cerebral infarction in young adults and was conducted on 71 consecutive young patients (aged 15–45 years) affected by a cerebral infarct who were hospitalized for the first time and discharged at least 1 year before the study. Data about risk factors, etiology, side and territory of stroke, social characteristics of the patient (age, sex, profession, educational level, family situation), poststroke seizures, recurrent stroke, other vascular events, and deaths were collected. Neurological deficits were graded with the National Institutes of Health (NIH) Stroke Scale. Poststroke depression (PSD) was quantified using the DSM-IIIR criteria and the Montgomery Asberg Depression Rating Scale. Outcomes were rated with the Ranking Scale, the Barthel Index and the Glasgow Outcome Scale. Quality of life was assessed with the Sickness Impact Profile. Follow-up information was obtained by interview and neurological examination. Follow-up information was obtained in 65 patients at a mean of 31.7 ± 13.0 (range 12–59) months, as 2 patients died and 4 were lost to follow-up and were thus excluded from this study. Poststroke seizures occurred in 7 patients (10.8%) and recurrent strokes in 4 patients (6.2%), but none were fatal. The outcome after stroke among survivors was usually good, since more than two-thirds of the patients (69.8%) reported no problem, 11.1% moderate handicap and one-fifth major handicap. Forty-six patients (73%) returned to work; the time period ranging from several days after stroke to 40 months, with a mean of 8 months. However, adjustments in their occupation were necessary for 12 patients (26.1%). PSD was common, since 48.3% of the patients were classified as depressed. PSD was associated with the localization of the infarct (carotid territory), a severe disability, a bad general outcome, and an absence of return to work. Their opinion about their quality of life was negative among approximately 30% of the patients, especially in emotional and alertness behaviors, social interaction, recreation and pastimes.The general outcome after cerebral infarct in young adults is usually good. However, the risk of a PSD is high, and only half of the patients had returned to their previous work. A remaining psychosocial handicap and depression of sexual activity impaired the quality of life. In multivariate analysis, a low NIH score at admission is a significant predictor for return to work, the absence of PSD, and a good quality of life.
Leukocyte Count and Aggregation during the Evolution of Cerebral Ischemic Injury
Authors: Silvestrini Mauro , Pietroiusti Antonio , Troisi Elio , Franceschelli Laura , Piccolo Paola , Magrini Andrea , Bernardi Giorgio , Galante Alberto
Published: April 2003

We evaluated leukocyte aggregation by means of the leukergy test and count in 26 patients with atherothrombotic stroke and in 10 patients with transient ischemic attacks. The evaluation was performed within 24 h from the onset of symptoms and then repeated on day 2, 4, 6 and 8. Data were compared with those of 10 healthy controls. Stroke patients were followed until day 30 when a clinical examination and brain computed tomography were performed to evaluate the extent and outcome of cerebral damage. Both leukocyte aggregation and count were significantly increased in stroke patients with respect to controls. While leukocyte count was not able to differentiate the severity of neurological impairment in stroke patients, leukocyte aggregation was significantly higher in major than in minor stroke patients on days 2 and 4 (p < 0.05). Moreover, while values of leukocyte count recorded at entry remained substantially stable in the following determinations in all groups, leukocyte aggregation showed a significant increase (p < 0.05) on day 4 with respect to all the other determinations in major stroke patients. These findings show that the extent and temporal profile of changes in leukocyte count and aggregation are different in patients with cerebrovascular disease and suggest an involvement of altered leukocyte rheology in the development of cerebral ischemic injury.
Clinical Predictors of Early Embolic Recurrence in Presumed Cardioembolic Stroke
Authors: Arboix Adrià , García-Eroles Luis , Oliveres Montserrat , Massons Juan B. , Targa Cecilia
Published: April 2003

Background: We determined clinical predictive factors of in-hospital embolic recurrence in presumed cardioembolic stroke patients by means of multivariate analysis based on clinical and neuroimaging prognostic variables assessed within 48 h of stroke onset. Methods: Data of 347 consecutive patients with presumed cardioembolic stroke included in a prospective stroke registry were collected. Demographic characteristics, clinical events, and outcome in the recurrent and nonrecurrent embolization group were compared. The independent predictive value of each variable on the development of early embolic recurrence was analyzed in two multiple liner regression models – one based on eight demographic, anamnestic, and clinical variables and another based on 10 clinical, neuroimaging, and outcome variables. Results: In-hospital recurrent embolization was diagnosed in 25 (6.9%) patients. The latency period was 12.1 days. The overall in-hospital mortality was 70.8% in the recurrent embolization group and 24.4% in the nonrecurrent embolization group (p < 0.001). Alcohol abuse, the combination of hypertension, valvular heart disease, and atrial fibrillation, nausea and vomiting, and previous cerebral infarction were predictors of recurrent embolization in the model based on clinical variables. In addition to these four variables, cardiac events were selected in the model based on clinical, neuroimaging, and outcome variables. Conclusions: A small number of clinical features that can be easily obtained on the patient’s initial assessment may help clinicians to identify a subgroup of patients with cardioembolic stroke at the highest risk of developing early recurrent brain or systemic embolization.
True Fungal Mycotic Aneurysm of the Basilar Artery: A Clinical and Surgical Dilemma
Authors: Watson Joe C. , Myseros John S. , Bullock M. Ross
Published: April 2003

Mycotic aneurysms of the intracranial circulation of true fungal etiology are extremely rare and are associated with a very high mortality. We report a case of a fatal aneurysm of the basilar artery secondary to Scedosporium apiospermum infection. The medical and surgical treatments are presented to demonstrate the difficulties associated with these lesions.
Transient Muteness Followed by Dysarthria in Patients with Pontomesencephalic Stroke
Authors: Orefice Giuseppe , Fragassi Nina A. , Lanzillo Roberta , Castellano Annalisa , Grossi Dario
Published: April 2003

Dysarthria is the principal motor abnormality following vascular damage to pontine paramedian structures, owing to the involvement of corticobulbar fibres. Here we describe 2 cases of adults affected by dysarthria following transient muteness as the result of a stroke in pontomesencephalic structures. Their clinical outcome was very similar to that of young patients who have undergone surgery of the 4th ventricle. Recently the importance of pons involvement has also been underlined in these cases. This case report suggests the existence of a functional network for speech, in which the pontomesencephalon is an important station for the triggering and the efficacy of verbal production.
Potential Usefulness of Basic Fibroblast Growth Factor as a Treatment for Stroke
Authors: Ay Hakan , Ay Ilknur , Koroshetz WalterJ. , Finklestein SethP.
Published: April 2003

Within the past few years, a growing body of evidence has accumulated indicating that exogenously administered neurotrophic growth factors may limit the extent of acute ischemic neural injury and enhance functional neurorecovery following stroke. One of the most widely studied growth factor in this regard is basic fibroblast growth factor (bFGF). In preclinical studies, bFGF administered intravenously within hours after the onset of ischemia reduces infarct size, presumably due to direct protection of cells at the borders (penumbra) of cerebral infarction. On the other hand, if bFGF is administered intracisternally starting at one day after ischemia, infarct size is not reduced, but recovery of sensorimotor function of the impaired limbs is increased, presumably due to enhancement of new neuronal sprouting and synapse formation in the intact uninjured brain. Clinical trials of the intravenous administration of bFGF as a cytoprotective agent in acute stroke are in progress. Trials of the delayed administration of bFGF as a recovery-promoting agent in subacute stroke are anticipated.
Stroke Treatment Guided by Transcranial Doppler Monitoring in a Patient Unresponsive to Standard Regimens
Authors: Behrens S. , Daffertshofer M. , Hennerici M.G.
Published: April 2003

Today secondary prevention of stroke is based on large clinical trials with the disadvantage of a lack of individual pathophysiological aspects. This is mainly due to the difficulty in identifying the source of stroke reliably and rapidly in these patients. Recurrent microembolic events detected by transcranial Doppler monitoring (TCM) has been suggested to individualize treatment. We describe a patient with recurrent ischemic events in the posterior circulation. Repeated TCM of the PCA disclosed microembolic events in the course of an acute embolic lesion pattern demonstrated by MRI. Detection of high-intensity transient signals by TCM provided a useful guidance of pathophysiologically oriented treatment in this patient.
Venous Microemboli in Patients with Artificial Heart Valves
Authors: Georgiadis D. , Baumgartner R.W. , Uhlmann F. , Lindner A. , Zerkowski H.R. , Zierz S.
Published: April 2003

Background: Detection of microemboli signals (MES) in patients with artificial heart valves has been extensively described, but the underlying material remains unclear. We assumed that the detection of MES in the jugular vein of patients with prosthetic valves would clearly argue for gaseous embolic material, since formed emboli are unable to cross through the capillaries. Methods and Results: Twenty-five patients with artificial heart valves, 15 patients with asymptomatic carotid artery disease, and 25 normal controls were examined. Monitoring was performed simultaneously over the dominant jugular vein and the ipsilateral middle cerebral artery for 30 min per subject, using 2-MHz transducers of a color duplex scanner for the jugular vein and a pulsed-wave Doppler for the middle cerebral artery. Data were harvested in an eight-channel digital recorder and MES counts evaluated by two separate observers. MES prevalence in the middle cerebral artery was 100, 13 and 0% in patients with artificial heart valves, asymptomatic carotid artery disease, and normal controls, respectively. No MES were detected in the jugular veins of patients with carotid artery disease or in normal controls, while their prevalence was 68% in patients with artificial heart valves. The interobserver agreement was satisfactory. Conclusion: Our results suggest that the embolic material of at least a part of MES in patients with artificial heart valves is gaseous.
Indomethacin for Brain Edema following Stroke
Authors: Schwarz Stefan , Bertram Markus , Aschoff Alfred , Schwab Stefan , Hacke Werner
Published: April 2003

Conventional therapies for raised intracranial pressure (ICP) frequently are not effective. We report a patient with raised ICP following a large hemispheric stroke. After conventional therapies had failed, indomethacin was repeatedly administered. After bolus infusion (50 mg), the ICP fell by a mean of 8.1 mm Hg, and the mean arterial blood pressure increased by a mean of 7.1 mm Hg, leading to a mean increase in the cerebral perfusion pressure by 15.3 mm Hg. After 1 h, the ICP had returned to baseline values after most infusions. Continuous infusion of indomethacin was not effective. We conclude that indomethacin may reduce elevated ICP over a short time in patients with ischemic brain edema even after conventional therapy has failed.
Clopidogrel for Cerebrovascular Prevention
Authors: Paciaroni Maurizio , Bogousslavsky Julien
Published: April 2003

Ischemic stroke, myocardial infarction and peripheral arterial disease are different clinical manifestations commonly due to the same underlying disease, i.e. atherosclerosis with subsequent thrombosis/embolism (atherothrombosis). Many clinical trials of secondary prevention after stroke or TIA have evaluated the benefit of long-term use of antiplatelet drugs in reducing the risk of subsequent vascular events. Aspirin and triclopidine have been shown to be effective in placebo-controlled studies for the composite outcome of stroke, myocardial infarction, or vascular death. Contrasting with these benefits, there were potentially serious, though rare, adverse effects. These considerations certainly justify the development of new antiplatelet agents. Clopidogrel is a new ADP-receptor antagonist, with a greater activity in animal models of thrombosis. CAPRIE (Clopidogrel versus Aspirin in Patients at Risk of Ischemic Events) was a randomized, blinded, international trial designed to assess the relative efficacy of clopidogrel and aspirin in reducing the risk of the outcome cluster of ischemic stroke, myocardial infarction, or vascular death, as well as to assess their relative safety. 19,185 patients were recruited. The intention-to-treat analysis showed that the relative risk reduction was 8.7% (95% CI 0.3–16.5, p = 0.043) in favor of clopidogrel from an overall annual event rate of ischemic stroke, myocardial infarction, or vascular death, ranging from 5.83% in the aspirin group to 5.33% in the clopidogrel group. The percentage of adverse events reported was higher in the aspirin group for all categories except rash, diarrhea, and abnormal liver function. It seems likely that clopidogrel will replace ticlopidine for stroke prevention, because of its better safety profile, and comparable efficacy. Clopidogrel probably will not replace aspirin as the first line therapy for many clinicians because of its higher cost and lack of widespread experience. However, other clinicians have already decided that they will use clopidogrel as first choice, because of the significant advantage over aspirin demonstrated in the CAPRIE study.
Hyperacute Diffusion-Weighted MRI in Basilar Occlusion Treated with Intra-Arterial t-PA
Authors: Nighoghossian N. , Derex L. , Turjman F. , Honnorat J. , Lucain P. , Berthezene Y. , Artru F. , Froment J.C. , Trouillas P.
Published: April 2003

Basilar artery thrombosis should be diagnosed immediately, as intra-arterial thrombolysis might improve the outcome. Diffusion-weighted (DWI)-MRI and three-dimensional time-of-flight MR angiography (3D TOF Turbo MRA) may provide additional insight into the extent of ischemia and the level of the occlusion. These methods could be helpful in the early classification of vertebrobasilar stroke, thus reserving the use of conventional angiography and possible intra-arterial thrombolysis for patients who had a severe clinical picture explained by preliminary assessments. We report the case of a 74-year-old woman who experienced a basilar artery occlusion; DWI-MRI and 3D TOF Turbo MRA provided noninvasive information concerning the level of arterial occlusion and its parenchymal ischemic impact, this leading to an intra-arterial thrombolytic therapy. These data suggest the feasibility of a noninvasive urgent diagnostic and prognostic approach with DWI-MRI and 3D TOF Turbo MRA in basilar occlusion.
Hippocampal Damage in the Human Brain after Cardiac Arrest
Authors: Fujioka Masayuki , Nishio Kenji , Miyamoto Seiji , Hiramatsu Ken-Ichiro , Sakaki Toshisuke , Okuchi Kazuo , Taoka Toshiaki , Fujioka Susumu
Published: April 2003

Background and Purpose: Very few reports are available on changes in the human hippocampus after cardiac arrest. The objective of this study was to investigate if specific hippocampal volume losses can be demonstrated in the human brain following reperfusion after cardiac arrest. Methods: We assessed the volumes of the hippocampal formation (HF) and temporal lobe excluding HF (TL) as the contrast using magnetic resonance (MR)-imaging-based volumetry in 11 vegetative patients after cardiac arrest and in 22 healthy controls of similar age, sex and body size distribution. The measured volumes were normalized for differences in the head size among subjects by dividing by the total intracranial volume (TICV). The MR images of the 11 patients were obtained between days 8 and 21 after cardiac arrest. Results: The observed volumes of HFs and TLs of both patient and control groups were as follows: right HF volume (HFV): 2.67 ± 0.19 (mean ± SD, cm3) in patients versus 3.89 ± 0.44 in controls; left HFV: 2.72 ± 0.17 versus 3.74 ± 0.35; right TL volume (TLV): 73.37 ± 6.54 versus 80.08 ± 7.62, and left TLV: 72.45 ± 6.77 versus 78.59 ± 6.68. The normalized indices (HFV/TICV and TLV/TICV) were as follows: right HF: 0.0021 ± 0.0002 (mean ± SD) in patients versus 0.0031 ± 0.0001 in controls, p < 0.0001, left HF: 0.0022 ± 0.0002 versus 0.0030 ± 0.0001, p < 0.0001, right TL: 0.058 ± 0.002 versus 0.064 ± 0.004, p = 0.0007, and left TL: 0.058 ± 0.002 versus 0.062 ± 0.004, p = 0.0014. The HFV-TLV ratios (HFV/TICV divided by TLV/TICV) of both groups were: right HFV-TLV ratio: 0.037 ± 0.004 in patients versus 0.049 ± 0.004 in controls, p < 0.0001, left HFV-TLV ratio: 0.038 ± 0.004 versus 0.048 ± 0.004, p < 0.0001. Conclusions: The patient group had HFs that were 26.8–30.6% smaller than those of the control group, but in the patient group, the TLs slightly decreased in size by only 7.8–8.2% of the volume of those in the control group within 21 days after cardiac arrest. The volume reductions in the bilateral HFs of patients after cardiac arrest were significantly larger than those in the bilateral TLs. We speculate that this specific rapid hippocampal shrinkage reflects its greater vulnerability to global brain ischemia.
Stick to the Rules
Authors: Lenzi D. , Lenzi G.L.
Published: April 2003

A young patient under ACO (anticoagulant) therapy with acute embolic stroke is presented, and therapeutic rules are discussed.
Cholesterol Reduction and Stroke Occurrence: An Overview of Randomized Clinical Trials
Authors: Di Mascio Rocco , Marchioli Roberto , Tognoni Gianni
Published: April 2003

We performed a meta-analysis of randomized clinical trials of more than 6 months duration to describe how fatal and nonfatal strokes are related to cholesterol lowering and to the type of intervention. A total of 41 individual trials including approximately 80,000 subjects and followed for an average of about 4 years were included in the overview. There was a 16% (95% CI, 7–25%) reduction in risk of stroke among treated patients compared to control patients (test for heterogeneity, p = 0.76). When trials that used different interventions were separately examined, a significant reduction in stroke occurrence was observed only for those using statins as active treatment (risk reduction 23%; 95% CI 13–33%). A variance-weighted regression analysis of the logarithmic odds ratios for stroke incidence against the percentage of cholesterol reduction indicated that a reduction of fatal and nonfatal stroke can be obtained for a cholesterol reduction of 9% (95% CI 6.8–13.6%). The combined data of primary and secondary prevention trials indicate that a large reduction of blood cholesterol, achievable with statin drugs, can reduce the incidence of stroke.
Clinician’s Biases toward Surgery in Cerebellar Hematomas: An Analysis of Decision-Making in 94 Patients
Authors: Wijdicks Eelco F. M. , St. Louis Erik K. , Atkinson John D. , Li Hongzhe
Published: April 2003

Background and Purpose: No studies have examined clinical decision-making in cerebellar hemorrhages. Clinical and CT features may influence surgery in patients with a spontaneous cerebellar hematoma. One commonly accepted adage is to remove a clot when 3 cm or larger in axial diameter on presentation CT scan. It is possible that certain preferences impact on outcome. Methods: We analyzed 94 patients with spontaneous cerebellar hematomas between the years of 1973–1993. Thirty-one patients underwent suboccipital craniectomy and clot removal with or without ventriculostomy. Deterioration denoted worsening of consciousness, new brainstem signs, or presentation in coma. Statistical analysis was performed utilizing a tree-based model fitted by binary recursive partitioning. Ninety-five percent confidence intervals (CI) were calculated. Results: The overall probability of surgical intervention was 33% (CI 23–43%). The chance of surgery in stable patients was 7% (CI 2–20%). Neurologic deterioration was seen in 54 patients (57%) and increased the prospects of a surgical procedure (52%, CI 38–66%). Surgery was performed in all deteriorating patients with small hematomas (size <3 cm), but large clots (size >3 cm) did not substantially influence surgical decision-making (45%, CI 30–60%) except in patients younger than 70 years old (57%, CI 41–82%). Conclusions: Clinicians at our institution usually wait for clinical deterioration to unfold prior to operating on patients with cerebellar hematomas. After deterioration occurs, they prefer small hematomas but will operate on large hematomas when patients are younger than 70, generally withholding surgery from older patients. These attitudes may impact on outcome and should be considered in future treatment trials.
Intrathecal Administration of Thrombin Inhibitor Ameliorates Cerebral Vasospasm
Authors: Kudo Akira , Suzuki Michiyasu , Kubo Yoshitaka , Watanabe Mikio , Yoshida Kenji , Doi Mamoru , Kuroda Kiyoshi , Ogawa Akira
Published: April 2003

The role of thrombin as a spasmogen after subarachnoid hemorrhage was evaluated using the intrathecally administered thrombin inhibitor hirudin, released from a drug delivery system (DDS) based on collagen in a canine vasospasm model. The DDS was implanted into the cisterna magna with autologous blood in the hirudin-treated group. The reduction in the angiographical diameter of the basilar artery was only 19% in the hirudin-treated group on day 7, showing a significant difference between hirudin-treated and nontreated groups (p < 0.01). These results suggest that thrombin is an important cause of vasospasm. The collagen DDS has great potential for treatment in the cerebrospinal fluid milieu.
Thalamic Hematoma from a Ruptured Posterior Cerebral Artery Aneurysm
Authors: Crum Brian A. , Wijdicks Eelco F.M.
Published: April 2003

Background: The location of parenchymal hemorrhage often indicates the site of the aneurysm in subarachnoid hemorrhage. Case Report: We present the first case of a thalamus hematoma associated with a small ruptured (P1) posterior cerebral artery aneurysm with rapid washout of subarachnoid blood mimicking a ganglionic hemorrhage. Conclusion: Thalamus hematoma with subarachnoid hemorrhage points at a ruptured proximal posterior circulation aneurysm.
Patient Understanding of Genetic Principles and Their Expectations of Genetic Services within the NHS: A Qualitative Study
Authors: Emery Jon , Kumar Satinder , Smith Helen
Published: April 2003

Objectives: To explore patients’ accounts of their understanding of heredity and genetic risk, the information patients believe they require to understand inherited disease, and their expectations and attitudes towards the provision of genetic services in the NHS. Method: Qualitative study using semi-structured, in-depth interviews of 19 patients with a family history of colorectal cancer referred to the Wessex regional cancer genetics clinic. Results and Interpretation: Three important themes emerged from the data: (1) Understanding genetics. (2) Making sense of genetic risk. (3) The role of primary care in genetics. Patients’ understanding of genetics is often disparate from the scientific explanation, but they feel it is unnecessary to understand basic principles of genetics to make sense of their family history of cancer. When presented with genetic risk in numerical terms, patients reformulate this information and reconstruct their risk according to personal and family experiences of cancer and personal understanding of inheritance. Although not scientifically accurate, patients’ conceptualisation of risk provides a framework on which to plan ways to reduce their own and their family’s risk of cancer. Patients perceive general practitioners predominantly as gatekeepers to secondary care with primary care currently unprepared to deal with genetic issues. Conclusions: This study has generated some important hypotheses relating to patients’ attitudes towards the role of primary care in genetics, and to communicating information about genetics and risk. Further research is required to explore the acceptability of genetic advice in primary care, and the value of discussing genetic risk in relation to patients’ beliefs about inheritance.
Genetic Testing for Cancer Risk: A Population Survey on Attitudesand Intention
Authors: Ulrich Cornelia M. , Kristal Alan R. , White Emily , Hunt Julie R. , Durfy Sharon J. , Potter John D.
Published: April 2003

Objective: Genetic testing for cancer risk will shortly enter medical practice. Our intent was to increase the understanding of the public’s attitudes towards and potential demand for genetic testing. Methods: We conducted a random-digit-dial survey of 1,450 adults in Washington State to assess the public’s attitudes toward genetic testing for cancer risk and to investigate correlates of intention to be tested for breast cancer risk (women) and prostate cancer risk (men). No specific genes were mentioned, as the intent of the survey was to understand the general interest in screening for genetic risks. The survey addressed familiarity with genetic testing, intention to be tested for breast or prostate cancer risk (when tests become available), benefits and risks associated with genetic tests, and who should have access to test results. Results: Most respondents expressed the intention to be tested for breast or prostate cancer risk (women 76%, men 83%). Most women (83%) and men (74%) would give the results to their primary care physician, but fewer believed that the test results should be available to their employer (women 5%, men 9%), their health insurer (women 32%, men 31%), or family members (women 42%, men 43%). Over 60% worried that discrimination could arise from genetic testing. Correlates of intention to be tested for breast cancer (women) included a family history of breast cancer, lower education, poor health, a history of mammography screening, and more physician visits in the past year. Among men, correlates of intention to test for prostate cancer included higher income, previous cancer diagnosis, a history of PSA screening, and more physician visits in the past year. Respondents who strongly believed in the benefits of genetic testing, who perceived themselves at greater risk for having a gene that increases risk, or who were less worried about discrimination expressed greater intent to be tested. Conclusions: Our survey suggests that the demand for genetic tests for cancer risk may be high, although confidentiality of test results is a major concern. Health care providers, genetic counselors, and research institutions should prepare strategies and policies for genetic testing and counseling as these tests enter general medical practice.
Assessment of Family Cancer History Collection and Utilization in Patient Care
Authors: Allen Howard J. , Briceno Cesar A. , Piver M. Steven
Published: April 2003

Objectives: This study was conducted to determine whether patients and accompanying persons visiting the Gynecologic Oncology Clinic were aware if a family cancer history was recorded and utilized in their medical care; whether they were aware of the importance of a family cancer history, and whether they would like to learn more about familial cancer. Methods: Sixteen- and 17-item self-report questionnaires were administered to patients and their accompanying persons, respectively, who were visiting the Gynecologic Oncology Clinic. All responses were anonymous. Results: Two hundred forty-four patient questionnaires and 114 accompanying person questionnaires were completed. Seventy-eight percent of the patients and 70% of the accompanying persons replied that a physician had inquired about their family history of cancer. Only 40% of those patients and 70% of those accompanying persons (31 and 49% of total patients and accompanying persons, respectively) replied that the inquiry was by their family physician. Sixty-seven percent of these patients and 63% of these accompanying persons reported that a written record was made of the family history. Thirty-one percent of the patients and 28% of accompanying persons knew that their family cancer history information had been used to aid in their medical care. Eighty-eight percent of the patients and 83% of the accompanying persons reported the occurrence of at least one relative with cancer; however, only 44% of the patients and 35% of the accompanying persons replied that a health care provider had ever provided teaching about the importance of a family cancer history. Seventy-five percent of the patients and 73% of the accompanying persons indicated that they would like to learn more about hereditary cancer and cancer genetics. Conclusions: This study demonstrates that patients desire information about cancer genetics and hereditary cancer. Therefore, health care providers should provide better education and information to their patients as well as improve their family history-taking skills.
The Hungarian Periconceptional Service as a Model for Community Genetics
Authors: Czeizel A.E. , Dobó M. , Dudás I. , Gasztonyi Z. , Lantos I.
Published: April 2003

Objectives: This review describes the methods and results of the Hungarian periconceptional service consisting of counselling, examinations and medical interventions. (The term periconceptional is used instead of preconceptional because the early postconceptional period is also involved to this service.) Methods: The service was based on three steps: check-up examination of reproductive health (i.e., preconceptional screenings), a 3-month preparation for conception, dispensed and/or supervised by qualified nurses, and a better protection in early pregnancy for the most sensitive early development of the embryo for voluntary and eligible couples. Results: Experiences from the coordinating centre of the Hungarian periconceptional service are summarized between February 1, 1984, and January 31, 1999, thus 15 years. Participants with positive family histories, case histories and subjects with genito-urinary infections had a more effective flow towards secondary care. Infertile couples were diagnosed and treated sooner. The periconceptional service is effective for the introduction of periconceptional folic acid-containing multivitamin supplementation and for the reduction of smoking and alcohol consumption in females in the preconceptional period. The rate of major congenital abnormalities (20.6 per 1,000) was significantly lower than expected. Conclusions: The periconceptional service is feasible and has many benefits. Thus, proper preparation for conception is the earliest and probably the most important effort to prevent genetic diseases.
Down Syndrome and Parity
Authors: Clementi M. , Bianca S. , Benedicenti F. , Tenconi R.
Published: April 2003

Objective: To investigate the effect of parity on Down syndrome (DS). Methods: The study was conducted on data from Northeast Italy (NEI) (1981–1996) and Sicily (ISMAC) (1991–1996) Congenital Malformation Registries. In these areas, all DS births are recorded and confirmed by chromosomal analysis; the NEI Registry also registers pregnancy terminations (TOPs) after prenatal diagnosis of DS. In order to estimate the effect of parity independently of the mother’s age and to reduce the truncation effect, different age classes and three classes of parity (1, 2–4, >4) were defined. Results: The study sample consisted of 1,088 consecutive newborns and 169 consecutive fetuses affected by DS. In both NEI and ISMAC samples, we found a significantly increased risk of having a DS child for multiparas ≥35 years of age. In the NEI sample, the inclusion of TOP data did not seem to modify this finding. In the ISMAC sample, a significantly reduced risk for primiparas was found at all ages. Conclusions: Our data confirm a higher risk of having a DS child in women with parity >4. As this effect is evident only in women ≥35 years age, its practical impact is null because these women are usually offered prenatal diagnosis in any case. However, the mechanisms involved, if this association is true, are very intriguing and the observation should stimulate scientific studies allowing a better knowledge of the nondisjunction mechanism.