bluuebunny/crossref_metadata_2025 huggingface dataset:
Pre-Attentive Discriminability of Sound Order as a Function of Tone Duration and Interstimulus Interval: A Mismatch Negativity Study
Authors: Tervaniemi Mari , Radil Tomas , Radilova Jirka , Kujala Teija , Näätänen Risto
Published: April 2003

The present study addressed the pre-attentive processing of sound order. Event-related potentials were recorded from reading subjects while they were presented with pairs of two tones differing from each other in frequency (1000 vs. 1500 Hz). The within-pair (silent) interstimulus interval (ISI) was, in separate blocks, varied between 0 and 245 ms to determine the minimum separation in time needed for detecting the reversed order of the two frequencies. In standard tone pairs (p = 0.9), the frequencies were in an ascending order, whereas in the deviant pairs (p = 0.1), their order was reversed. Tone durations of 5 and 20 ms were employed in separate experiments. With the 20-ms stimulus duration, the change-specific mismatch negativity (MMN) component was elicited with all within-pair ISIs employed (0, 10, 30, 90 ms). With the 5-ms stimulus duration, however, MMN was elicited only with the 245-ms ISI but not with 95-ms or shorter ISIs. These results show that increased stimulus duration considerably improves perceiving the order of two tones at the pre-attentive level. They also indicate that the accuracy of the processing of temporal information can be probed with MMN. This finding, together with the fact that MMN elicitation does not require the subject’s voluntary attention, suggests that MMN might be used in the assessment of temporal processing deficits in clinical disorders in which patients are not motivated or able to give their verbal or motor response.
Trained Discrimination of Temporal Patterns: Cochlear Implants in Gerbils
Authors: Kadner Alexander , Scheich Henning
Published: April 2003

The purpose of this study was to establish an animal model for the discrimination of temporal order cues contained in electrical stimuli to the cochlea. Gerbils were deafened and implanted in the right cochlea with a single platinum stimulating electrode. Two groups of animals were trained in a two-way active avoidance shuttle box paradigm to discriminate downward from upward interval-modulated pulse trains (1–100 ms). One group consisted of naive animals. The other group had previously been trained in the same shuttle box (same behavioral meaning) to discriminate identical pulse trains presented acoustically. Significant discrimination performance was found in the group of naive animals. However, over the 6-day training period, animals with previous acoustic experience achieved no significant discrimination performance. This suggests that temporal order cues in pulse trains can be used in cochlear implants to transmit behaviorally relevant information but that this may be in conflict with relevant auditory preexperience.
A Simple Two-Component Model of the Electrically Evoked Compound Action Potential in the Human Cochlea
Authors: Lai Wai Kong , Dillier Norbert
Published: April 2003

Neural response telemetry (NRT) permits in situ intracochlear recordings of the electrically evoked compound action potential from the auditory nerves using scala tympani electrodes. The recorded NRT waveforms can generally be categorized under either single positive peak or double positive peak waveforms. This is similar to the observations from Stypulkowski and van den Honert, who suggested that the double peak complex arises from two components that could be axonal and dendritic in origin, respectively. Using a simple mathematical model which linearly combines two separate waveforms similar in shape but differing in amplitude and latencies, it was possible to simulate the various NRT waveform categories. The simulation results support the view that the two waveform components originate from dendritic or axonal processes and implies that the shape of the response waveform may provide information about the degree of neural survival in the stimulated cochlea. This information could be useful for determining optimal speech coding parameters for cochlear implant users on an individual basis.
Growth Characteristics of Breast-Fed Compared to Formula-Fed Infants
Authors: Dewey Kathryn G.
Published: April 2003

In affluent populations, breast-fed infants generally exhibit a different pattern of growth than formula-fed infants. The average weight gain of the former is lower than that of the latter, even after complementary foods are introduced. In some studies, the length gain is also lower among breast-fed infants, whereas in others there is no significant difference in linear growth between feeding groups. Growth in head circumference does not differ by feeding mode. Because of the difference in weight gain, breast-fed infants are generally leaner than formula-fed infants by 12 months of age. Breast-fed infants appear to self-regulate their energy intake at a lower level than consumed by formula-fed infants and have a lower metabolic rate. Evidence to date suggests that there are no apparent adverse consequences associated with the lower intake and slower weight gain of breast-fed infants: compared to formula-fed infants, they do not differ in activity level, and they experience less illness and appear to have enhanced cognitive development. The reasons for differences in growth patterns by feeding mode require further research.
Xanthine Oxidoreductase Gene Expression and Enzyme Activity in Developing Human Tissues
Authors: Saksela Mika , Lapatto Risto , Raivio Kari O.
Published: April 2003

Xanthine oxidoreductase (XOR) has been implicated in tissue injury following ischemia-reperfusion because of its ability to generate reactive oxygen species under these conditions. In order to elucidate its role in various organs, we quantified the levels of XOR mRNA expression and activity in developing human tissues. XOR gene expression was highest in the intestine and in the liver, which also showed the highest enzyme activities. By a sensitive RNA-PCR assay, low levels of the transcript were detected in the kidney, lung, cardiac muscle, and brain of all subjects studied. XOR activities followed the mRNA distribution, being low or undetectable in tissues other than the liver and the intestine.
Cerebrospinal Fluid and Serum Nitric Oxide Levels in Asphyxiated Newborns
Authors: Ergenekon Ebru , Gücüyener Kıvılcım , Erbaş Deniz , Süheyl Ezgü Fatih , Atalay Yıldız
Published: April 2003

Hypoxic-ischemic encephalopathy (HIE) is the result of a chain of events caused mainly by cytokines and nitric oxide (NO) release, which is later on followed by free oxygen radical injury. To investigate NO involvement in asphyxiated newborns, serum and cerebrospinal fluid (CSF) values of NO levels in 17 neonates with HIE were detected. Infants at or above 37 weeks of gestation were classified to have mild, moderate and severe HIE due to Sarnat and Sarnat. Samples obtained between 24 and 72 h of life were immediately frozen at –70°C till the time of measurement by Sievers NOA. Five patients had mild, 6 patients had moderate and 6 patients had severe HIE, 4 in the severe HIE group also had multisystem involvement. The CSF NO levels were significantly higher in moderate and severe HIE groups compared to the mild HIE group (p = 0.028 and p = 0.018 respectively). Our results show that NO level increases in CSF with the severity of HIE between 24 and 72 h following asphyxia. According to the animal work, this is the time period where inducible NO synthase gets activated and could cause neurotoxicity, which might perhaps be prevented by interventions.
Similarities and Differences between the Effects of Amino Acids and Nitroprusside on Peritoneal Permeability during CAPD
Authors: Douma Caroline E. , Imholz Alexander L.T. , Struijk Dirk G. , Krediet Raymond T.
Published: April 2003

Objective: Intraperitoneal administration of amino acid based dialysis solutions affects the surface area available for diffusion, with almost no effect on the intrinsic permeability to macromolecules. Intraperitoneally administered nitroprusside affects the vascular surface area and the intrinsic permeability without effect on the peritoneal blood flow. In the present study, these differences were translated into different effects on the radii of the pores in the peritoneal membrane. Methods: Effects of amino acid based dialysate and nitroprusside on peritoneal permeability characteristics were evaluated in standard peritoneal permeability analyses with L-arginine-containing amino acid dialysate (10 patients) or with 1.36% glucose dialysate with nitroprusside (10 patients). In each patient a control experiment with 1.36% glucose was performed. Kinetic modeling was done to analyze the effects in terms of the pore theory. Results: Both interventions increased the mass transfer area coefficients of low molecular weight solutes. This is in accordance with an increase in the unrestricted area over diffusion distance found with modeling. With amino acids almost no effect was found on the protein clearances; the increase in the large-pore radius was only small. Nitroprusside induced a marked increase in protein clearances. This was in accordance with an evident increase in the average large-pore radius. Conclusions: Amino acids affect the radii of the small pores and the large pores to the same extent. Nitroprusside influences especially the large pores. Both amino acids and nitroprusside are vasoactive, although the effects on the peritoneal microcirculation are different.
Cardiac Function and Oxygen Balance in Septic Patients during Continuous Hemofiltration
Authors: Meloni Carlo , Morosetti Massimo , Turani Franco , Palombo Giuditta , Meschini Luciano , Zupancich Enrico , Taccone-Gallucci Massimo , Di Giulio Salvatore , Casciani Carlo U.
Published: April 2003

The aim of this work was to study hemodynamic, oximetric and metabolic parameters in septic patients during continuous hemofiltration, in order to determine whether the changes in hemodynamic parameters can influence the oxygen utilization in peripheral tissues. 29 multiple organ failure patients with septic shock were studied during the first 48 h of continuous hemofiltration: 18 were submitted to CAVH and 11 patients were treated with CAVHD to correct ARF and fluid overload. Our data show that RVEF improves and REDVI reduces progressively during treatment, together with a significant reduction of the cardiac index after 48 h of CAVH(D). There were no significant variations in oxygen tissue parameters, while plasma lactate was reduced significantly. In conclusion, our data confirm that continuous hemofiltration may be useful in septic patients to correct fluid overload and ARF, without affecting hemodynamic stability and oxygen balance. Moreover, in septic patients, this technique improves hemodynamics, reduces the filling pressure in the right heart and reduces hyperdynamic response as CI and SVRI, without any negative effects on O2 balance.
Effects of Hemodialysis on Circulating Adrenomedullin Concentrations in Patients with End-Stage Renal Disease
Authors: Toepfer M. , Schlosshauer M. , Sitter T. , Burchardi C. , Behr T. , Schiffl H.
Published: April 2003

To characterize the determinants of circulating levels of adrenomedullin (AM), the plasma levels of this peptide were measured in 58 patients with end-stage renal disease on hemodialysis. Predialysis plasma levels of AM were more than twice as high in patients on hemodialysis as compared to controls. In hemodialysis patients with heart failure (NYHA classes II–IV) or hypertensive HD patients plasma levels of AM were significantly higher than in patients with end-stage renal disease only. Plasma levels of AM were not altered immediately by hemodialysis but decreased significantly 14–20 h after hemodialysis. AM plasma levels before hemodialysis and 14–20 h after hemodialysis were correlated with the corresponding mean arterial pressure.
Reduced Blood bcl-2 Protein Concentration in Patients on Hemodialysis
Authors: Buemi M. , Allegra A. , Corica F. , Ruello M. , Di Pasquale G. , Aloisi C. , Giaccobe M.S. , Romeo A. , Frisina N.
Published: April 2003

The concentrations of bcl-2 protein that can block programmed cellular death in various cell lines were evaluated in blood samples from 10 uremic patients on hemodialysis, 10 uremics not yet on hemodialysis, and in 10 healthy controls. The bcl-2 protein variations (in uremics on dialysis) were ascertained in patients during the dialysis session. Oxidative stress was evaluated in all groups by assaying the products of intraerythrocytic lipoperoxidation. Dialyzed and nondialyzed uremic patients had higher bcl-2 protein concentrations than healthy subjects. Dialysis causes a significant reduction in the concentrations of bcl-2 protein which becomes statistically significant during the 3rd hour. In both groups of uremic patients a positive correlation was found between bcl-2 protein and products of lipoperoxidation.
Long-Term Extracorporeal Bilirubin Elimination: A Case Report on Cascade Resin Plasmaperfusion
Authors: Mertens Peter Rene , Schönfelder Thomas , Handt Stefan , Kierdorf Horst , Marschall Hanns-Ulrich , Busch Norbert , Heintz Bernhard , Sieberth Heinz-Günter
Published: April 2003

Acute hepatic failure develops as a disease entity of rather diverse origin. With disease progression, toxic bilirubin levels may cause severe complications which include AV-nodal blockage, cardiac arrhythmia, impaired consciousness, generalized seizures, and status epilepticus. Treatment choices to prevent clinical deterioration comprise of costly and limited available orthotopic liver transplantation, utilization of extracorporeal bioartificial liver support devices and haemoperfusion/plasmaperfusion treatment with activated charcoal/anion exchange filters. Here, we present a patient with acute drug-induced cholestatic hepatitis. Excessively elevated bilirubin levels were accompanied by cardiac and cerebral complications. Extracorporeal resin perfusion treatment (Plasorba, BR–350) was successfully performed over a 50-day period without activation of the coagulation system or side effects. Bilirubin levels were lowered to a minimum of 225 μmol/l, with concurrent clinical improvement. In conclusion, extracorporeal anion exchange plasmaperfusion may be a viable long-term treatment for hyperbilirubinaemic side effects in overt cholestatic hepatitis.
Low Density Lipoprotein (LDL) Modification: Basic Concepts and Relationship to Atherosclerosis
Authors: Sevanian Alex , Asatryan Liana , Ziouzenkova Ouliana
Published: April 2003

A large number of clinical studies support the hypothesis that the risk for atherosclerosis is associated with the proportion of different LDL subfractions in blood. Electronegatively modified forms of LDL (LDL–) isolated using different chromatographic techniques are characterised by significant differences in the protein and lipid content as compared to the native LDL subfraction. LDL– composition appears to influence its atherogenic properties as well as its high susceptibility to oxidation and impaired metabolism. Increased LDL– levels are found in subjects with coronary artery disease, particularly in diabetics and patients undergoing haemodialysis (HD). Whether elevated LDL– levels are due to the LDL oxidation in blood remains disputed despite the oxidative character of LDL– modification. Plausible means for LDL– formation in blood include glycation and protein-radical interactions with ApoB 100. The latter can prevail during HD as observed in in vitro studies using a model HD system. The rapid and progressive formation of LDL– during standard HD can be significantly reduced employing haemolipodialysis (HLD), which provides local delivery of specific antioxidants (vitamin E and C) to blood at concentrations above normal physiologic levels. This procedure appears to be more effective than oral supplementation with antioxidants and may be a promising approach to reducing the rapid progression of atherosclerosis in HD patients.
Evaluation of Pre- and Postdilutional On-Line Hemodiafiltration Adequacy by Partial Dialysate Quantification and On-Line Urea Monitor
Authors: Lim Paik-Seong , Lee Han-Pin , Kho Benny , Yu York-Leng , Chang Su-Ching , Lin Yu-Yu , Yang Chiu-Chin , Lin Yi-Tian , Wang Tsung-Hsiu , Kuo Shu-Yin , Lin Lung-Chin
Published: April 2003

On-line highflux hemodiafiltration (HDF) is a clinically interesting and effective mode of renal replacement therapy, which offers the possibility to obtain an increased removal of both small and large solutes. The fundamental role of urea kinetic monitoring to assess dialysis adequacy in conventional hemodialysis has been widely studied. Both direct measurement of the urea removed by the modified direct dialysate quantitation (mDDQ) based on partial dialysate collection (PDC) and dialysate-based urea kinetic modeling (DUKM) using urea monitor have been advocated. The validity of this assessment tool in the patients with on-line HDF remained unclear. The aims of this investigation were (1) to compare the delivered Kt/V, urea mass removal (UMR), solute removal index (SRI) and normalized protein catabolic rate (nPCR) between pre- and postdilutional high-flux HDF; (2) to verify and compare the efficiency of pre- and postdilutional HDF using DUKM with on-line dialysate urea sensor, and mDDQ with partial dialysate collection. During both mode of HDF, the paired analysis urea removed and Kt/V showed no significant difference. Using mDDQ, mean values for predilutional mode were as follows: Kt/V 1.53 ± 0.01 UMR, 16.8 ± 0.3 g/session; urea clearance 178 ± 18 ml/min; SRI 75.5 ± 7.7%; urea distribution volume (V) 28.3 ± 1.2 liters; nPCR 1.34 ± 0.18 g/kg/day; on the other hand, mean values for postdilutional mode were Kt/V 1.58 ± 0.01; UMR 17.10 ± 0.28 g/session; urea clearance 184 ± 21 ml/min; SRI 77.2 ± 3.5%; urea distribution volume, 27.8 ± 1.5 liters; nPCR 1.34 ± 0.19 g/kg/day. The mean value of urea generation rate was 5.82 ± 1.12 mg/min during HDF. Our results showed that dialysis adequacy was achieved with both high-volume predilutional HDF and postdilutional HDF. These two modes of HDF provided similar and adequate small solute clearance. In addition, we found that on-line analysis of urea kinetics is a reliable tool for quantifying and assuring delivery of adequate dialysis.
Analysis of Urea Nitrogen and Creatinine Kinetics in Hemodialysis: Comparison of a Variable-Volume Two-Compartment Model with a Regional Blood Flow Model and Investigation of an Appropriate Solute Kinetics Model for Clinical Application
Authors: Yamada Toshio , Hiraga Seigo , Akiba Takashi , Marumo Fumiaki
Published: April 2003

To investigate an appropriate solute kinetics model for clinical application, we analyzed urea nitrogen (UN) and creatinine (Cr) kinetics by a variable-volume two-compartmental model (2CM) and a regional blood flow model (RBF) in 44 hemodialysis patients with varying proportions of first compartmental volume and regional volume (p1). Solute kinetics could not be solved in some of the patients with higher p1 values, and there were more solution failures by the RBF than by the 2CM. The solute generation rate (g) and solute distribution volume in the dry state (VD) increased with increases in p1 in both models, but there were some differences between the two models. When g was normalized by VD, it became relatively constant, irrespective of the p1 value or model used (0.133 ± 0.029 mg/min/l by the 2CM and 0.132 ± 0.029 mg/min/l by the RBF for UN; 0.0200 ± 0.0049 mg/min/l by the 2CM and 0.0198 ± 0.0048 mg/min/l by the RBF for Cr). The intercompartmental mass transfer coefficient (Kc; liters/min) calculated by the 2CM decreased as p1 increased (Kc = –1.77·p1 + 1.16, p < 0.0001, R = 0.999 for UN; Kc = –0.847·p1 + 0.556, p < 0.0001, R = 1.000 for Cr). The systemic blood flow (Qsys; liters/min) calculated by the RBF also decreased as p1 increased (Qsys = –11.1·p1 + 6.21, p < 0.0005, R = 1.000 for UN; Qsys = –5.22·p1 + 2.90, p < 0.001, R = 0.999 for Cr). Since the RBF more frequently failed to solve the solute kinetics and since there was a difference in its Qsys values for UN and Cr, the 2CM was considered to be a superior model. When p1 was extremely low, the 2CM could be transformed into a modified variable-volume one-compartment model (1CM) which presented a similar g/VD (0.133 ± 0.029 for UN; 0.0200 ± 0.0048 for Cr). This modified 1CM was considered to satisfy appropriate conditions for clinical application, since it is simpler than the 2CM and provides useful information on the dialysis dose.
Clinical Pharmacokinetics and Effects of an Oral Sustained-Release Preparation of Disopyramide Prescribed for Patients Undergoing Maintenance Hemodialysis
Authors: Kaji Takashi , Nojima Yoshihisa , Arisaka Hiroaki , Naruse Takuji
Published: April 2003

Aims: We evaluated the clinical pharmacokinetics of a sustained-release preparation of disopyramide phosphate (DSR) and its effects on supraventricular arrhythmias in hemodialysis patients. Methods: Eight hemodialysis patients with either paroxysmal supraventricular tachycardia (PSVT) or PSVT plus paroxysmal atrial fibrillation (Paf) were given 150 mg of DSR 2 h before each hemodialysis. The frequency of PSVT, the duration of Paf before and 2 weeks after starting DSR and the blood concentration of the drug were evaluated. Results: There was no significant difference between serum levels of DSR before and after hemodialysis. The frequency of PSVT and the duration of Paf were significantly reduced by the therapy. Side effects and electrocardiographic abnormalities did not appear during the period. Conclusion: We conclude that hemodialysis does not remove DSR, and that a single dose of 150 mg of DSR given 2 h before hemodialysis is safe and sufficient to reduce the incidence of supraventricular arrhythmias.
Homocysteine as a Cardiovascular Risk Factor
Authors: Biasioli Stefano , Schiavon Renzo
Published: April 2003

Hyperhomocysteinemia (HH), a known risk factor for vascular diseases, is a frequent condition in hemodialysis (HD) patients. HH induces an oxidant stress to the vascular endothelium, causing a failure of vasodilation and an impairment of the antithrombotic properties. Vitamins B6, B12 and folic acid are important cofactors for the enzymes in the catabolism of homocysteine (Hcy). Failure of Hcy catabolism forces the cell to export Hcy into the plasma. The kidney is an important metabolic site for removal (up to 70%) of plasma Hcy (P-Hcy). HD lowers the P-Hcy concentration by 29 and 41% with cellulosic and noncellulosic membranes, respectively, yet values return to normal in only a few patients. Clearly, we must decrease the dangerous high levels of Hcy in different ways. Vitamin Supplementation: Vitamins B6, B12 and folic acid decreased the basal level of Hcy by about 40%, starting from the sixth month. Membranes: Some membranes performed better than the others. Techniques: On the chronic basis, in our 1-year experience, paired filtration dialyis led to the best results, when compared to bicarbonate dialysis and acetate-free biofiltration. Finally, as in HD patients no one type of treatment can normalize the P-Hcy concentration, we should try other, different strategies such as absorption, the use of liposomes and new types of supplementation.
Microbiologic Purity of Dialysate:Rationale and Te chnical Aspects
Authors: Canaud B. , Bosc J.Y. , Leray H. , Morena M. , Stec F.
Published: April 2003

Dialysate purity has become a major concern in hemodialysis since it has been shown that microbial-derived products were stimulating the production and the release of proinflammatory cytokines in hemodialysis patients. This chronic microinflammatory state induced by hemodialysis has been putatively implicated in the development of dialysis-related pathology. In order to prevent risk related to these offenders and to reduce patient/dialysis interaction, it appears highly desirable to use ultrapure dialysis fluid aiming at sterility and apyrogenicity on a regular basis. Ultrapure dialysate results from a complex chain of production where purity grade relies on the weaker link of this chain. Technical aspects and pitfalls in the production of ultrapure dialysate are summarized in this paper. Production of ultrapure dialysate may be achieved on a routine basis, provided adequate components are used, and hygienic handling is regularly ensured. It includes the use of ultrapure water, clean and or sterile electrolytic concentrates (liquid or powder), implementation of ultrafilters on hemodialysis machines, microbiologic monitoring and hygienic handling of the chain with frequent disinfection. Safety and reliability of ultrapure dialysate production relies on a continuous quality assurance process, where results are coupled to corrective action in a feedback loop process.
Diffusion Kinetics in Blood during Haemodialysis and in vivo Clearance of Inorganic Phosphate
Authors: Descombes Eric , Jutzet André , Perriard François , Fellay Gilbert
Published: April 2003

Contradictory data are reported in the literature concerning the diffusion kinetics of inorganic phosphates (iPh) between red blood cells and plasma during haemodialysis. Accordingly, we performed mass balance and equilibration studies to analyze the diffusion kinetics of iPh in vivo and in vitro. Mass balance analysis shows that iPh is only cleared from the plasma volume and thus that it practically does not diffuse from red blood cells to plasma during the short time lapse of blood transit through the haemodialyzer. In vitro equilibration studies of blood drawn at the filter outlet show that at room temperature there is a slow, limited, and almost linear net efflux of iPh during the 4 h that follow blood drawing. Our results point out: (1) that the in vivo clearance of iPh should be exclusively determined as plasma clearance, and (2) that for accurate clearance determinations the iPh concentrations should be measured in blood samples centrifuged within at most 1 h after blood drawing. Whole-blood clearance determinations – as well as the in vitro dialyzer data – largely overestimate (>30%) the real in vivo dialyzer performance.
Resource Limitations and Strategies for the Treatment of Uremia
Authors: Keshaviah Prakash
Published: April 2003

India has made great strides in health care since gaining independence in 1947. Much still needs to be done. Scarce health care resources are directed at priorities that include infant and maternal mortality, immunizations, malnutrition, communicable disease prevention, and access to protected water and sanitation. There is, therefore, no government reimbursement for treatment of patients with ESRD (estimated incidence of 100 per million population). Transplantation, the modality of choice in India, benefits only 2–3% of ESRD patients. Hemodialysis is primarily used short-term for pretransplant stabilization. A very small minority of patients is placed on maintenance hemodialysis or CAPD. The annual cost of renal replacement therapies is more than 10 times the per capita gross national product. Financial constraints pose ethical problems for the nephrologist related to adequate prescriptions and compliance. Preventing the progression of kidney disease and reducing the cost of disposables through indigenous manufacture are initiatives that need to be explored.
Identification of the WBSCR9 gene, encoding a novel transcriptional regulator, in the Williams-Beuren syndrome deletion at 7q11.23
Authors: Peoples R.J. , Cisco M.J. , Kaplan P. , Francke U.
Published: April 2003

We have identified a novel gene (WBSCR9) within the common Williams-Beuren syndrome (WBS) deletion by interspecies sequence conservation. The WBSCR9 gene encodes a roughly 7-kb transcript with an open reading frame of 1483 amino acids and a predicted protein product size of 170.8 kDa. WBSCR9 is comprised of at least 20 exons extending over 60 kb. The transcript is expressed ubiquitously throughout development and is subject to alternative splicing. Functional motifs identified by sequence homology searches include a bromodomain; a PHD, or C4HC3, finger; several putative nuclear localization signals; four nuclear receptor binding motifs; a polyglutamate stretch and two PEST sequences. Bromodomains, PHD motifs and nuclear receptor binding motifs are cardinal features of proteins that are involved in chromatin remodeling and modulation of transcription. Haploinsufficiency for WBSCR9 gene products may contribute to the complex phenotype of WBS by interacting with tissue-specific regulatory factors during development.
Venous Doppler Ultrasound Assessment of the Parasellar Region
Authors: Valdueza José Manuel , Hoffmann Olaf , Doepp Florian , Lehmann Rudolf , Einhäupl Karl Max
Published: April 2003

The purpose of this report is to present normal values for venous blood flow velocities from the parasellar region using transcranial Doppler ultrasound (2-MHz transducer) with both transtemporal and transorbital approaches and to examine the nature of previously reported low-pulsatility signals with velocities in the arterial range from this area. Forty-three subjects ranging in age from 18 to 56 years (mean ± SD, 31.9 ± 10.1 years) were examined. In all subjects, a venous signal directed away from the probe with the source lateral to the internal carotid artery siphon was detected on at least one side. A total of 72 parasellar venous signals were insonated. Signals were considered to belong to the main inflow and outflow vessels of the cavernous sinus. The mean blood flow velocity ranged from 6 to 81 cm/s (mean ± SD, 27.3 ± 17.4 cm/s). Typical transients in the Valsalva test confirmed the venous character of the signals. No significant gender, side-to-side or age dependency was observed. A separate analysis was done for venous high-velocity signals defined by a mean blood flow velocity greater than 30 cm/s. They were detected in 21 out of 43 subjects (48.9%) via a transtemporal approach and in 6 of them (14%) via the transorbital route, too. Again, no significant gender, side-to-side or age dependency was noted. In summary, we found a greater variability of venous blood flow velocities in the parasellar region compared to other basal cerebral veins, e.g. the basal vein of Rosenthal. The previously reported low-pulsatility signals with velocities in the arterial range proved to be of venous origin.
Experience with Diffusion-Weighted Imaging in an Acute Stroke Unit
Authors: Read S.J. , Jackson G.D. , Abbott D.F. , Syngeniotis A. , Mitchell L.A. , Fitt G.R. , Donnan G.A.
Published: April 2003

We performed diffusion-weighted MRI (DWI) on a standard 1.5-tesla MRI scanner using a high-speed stimulated echo pulse sequence (turboSTEAM) in 9 stroke patients and 9 control subjects to investigate whether this technique can be used clinically to assist in ischaemic stroke diagnosis within the time frame for potential therapy. Stroke patients underwent DWI between 3.75 h and 3 days after stroke onset. Three patients were studied on more than one occasion. DWI was normal in the 9 controls. Seven of 9 stroke patients showed areas of increased signal on DWI. DWI detected cerebral ischaemia 3.75 h after stroke onset when both CT and T2-weighted MRI were normal. In 6 DWI-positive patients studied at later times, increased signal on T2-weighted images was present at the same time. Two patients had normal CT, T2-weighted and DWI images; both made good neurological recoveries. For the routine assessment of stroke patients, DWI implemented on a standard MRI system can provide additional information of clinical value to that obtained with conventional pulse sequences. In particular it facilitates early detection of cerebral ischaemia during the first few hours after stroke.
The ECASS 3-Hour Cohort
Authors: Steiner Thorsten , Bluhmki Erich , Kaste Markku , Toni Danilo , Trouillas Paul , von Kummer Rüdiger , Hacke Werner
Published: April 2003

Objectives: (1) To determine whether and how outcome measurements in the ECASS trial are influenced by a shorter time window (0–3 vs. 3–6 h) between onset of symptoms and start of thrombolytic therapy using recombinant tissue plasminogen activator (rt-PA) in acute ischemic stroke. (2) To discuss the results of the ECASS 0- to 3-hour cohort with the results of the National Institute of Neurological Disorders and Stroke Study (NINDSS). Design and Analysis: Analysis of the 0- to 3-hour and the 3- to 6-hour cohort in accordance with the ECASS protocol. Comparative analysis of the ECASS and NINDSS results following the NINDSS protocol using dichotomized endpoints. Main Outcome Measures: Primary endpoints: modified Rankin Scale, Barthel Index; secondary endpoints: combined Barthel/Rankin, long-term Scandinavian Stroke Scale, National Institutes of Health Stroke Scale, mortality at 30 and 90 days, occurrence of intracranial hemorrhage. NINDS trial endpoint: favorable outcome as defined in the NINDS trial. Results: In ECASS, 87 patients were randomized within 3 h of stroke onset. Differences in favor of rt-PA treatment can be found for all primary and secondary outcome measures in the ECASS 0- to 3-hour cohort, except for mortality at day 30, which is somewhat higher in the rt-pA-treated group. However, due to the small sample size, the differences do not reach statistical significance. Early infarct signs (as defined by the ECASS protocol) are found as early as 2 h after stroke onset. Parenchymal hemorrhages are found significantly more often among rt-PA-treated patients. The results in the ECASS 0- to 3-hour cohort fit well with the results in NINDSS. Conclusion: Data from the 3-hour ECASS cohort support the efficacy of early thrombolytic therapy in acute hemispheric stroke patients. Comparing bleeding complications between the ECASS and NINDSS is difficult because of differences in the definition and occurrence of hemorrhagic events.
Is Another Clinical Trial Warranted Regarding Endarterectomy for Asymptomatic Carotid Stenosis?
Authors: Chaturvedi Seemant , Halliday Alison
Published: April 2003

Background: Several clinical trials regarding carotid endarterectomy for asymptomatic stenosis have been conducted in the past two decades. These research studies have not resolved the controversy regarding the optimal treatment of patients with this condition. Summary of review: We examine some of the reasons why there is persisting uncertainty regarding the value of carotid endarterectomy for asymptomatic stenosis. These include the sample size of earlier studies, the generalizability of these studies, and the clinical importance of the reported surgical benefits in some studies. We then review the rationale for another, larger clinical trial. Conclusions: The role of endarterectomy for asymptomatic stenosis remains an unsettled issue. A larger clinical trial may shed light on how to best identify which patients derive clinically significant benefits from prophylactic carotid artery surgery.
The Ege Stroke Registry: A Hospital-Based Study in the Aegean Region, Izmir, Turkey
Authors: Kumral Emre , Özkaya Bekir , Sagduyu Ayşe , Şirin Hadiye , Vardarli Egemen , Pehlivan Murat
Published: April 2003

We present the profile of risk factors, etiologic and clinical data of 2,000 consecutive patients with first-ever-in-a-lifetime stroke (cerebral infarction, cerebral hemorrhage and subarachnoid hemorrhage), admitted to the Ege University Hospital between January 1, 1991, and September 31, 1995. This hospital-based registry is the first systematic epidemiologic report on the stroke profile of Turkish people. The Ege University Stroke Unit is the only tertiary medical care facility which is organized for patients with different stroke subtypes in İzmir, Turkey. A prospective hospital-based registry using systematic computer coding of data of all stroke patients has been used since January 1991. All patients were evaluated by clinical examination, CT and/or MRI, color duplex and specific cardiac investigations. They were followed up for at least 6 months. The mean age was 62.3 ± 12 years, and 44.4% were females. Ischemic stroke was found in 77%, primary intracerebral hemorrhage in 19% and subarachnoid hemorrhage in 4%. The major risk factor of ischemic stroke was hypertension (63%), followed by hypercholesterolemia (37%), diabetes mellitus (35%), ischemic heart disease (23%), atrial fibrillation (20%) and smoking (17%). The main cause of primary intracerebral hemorrhage was hypertension (88%), and the principal localization was the thalamus (38%), followed by putamen (28%), lobar (16%), pons (6%), cerebellar (4%), primary intraventricular hemorrhage (4%) and multiple hemorrhages (2%). The overall 30-day case-fatality rate was 19.7% and the higher mortality rate was found in patients with primary intracerebral hemorrhage (29%) than in those with ischemic stroke (17%). The Ege Stroke Registry allows to estimate the stroke-related problems in patients admitted to a stroke unit and to evaluate the risk factors, etiology and clinical manifestations of stroke in Turkey.
Migraine with Aura and Right-to-Left Shunt on Transcranial Doppler: A Case-Control Study
Authors: Del Sette Massimo , Angeli Silvia , Leandri Massimo , Ferriero Giorgio , Bruzzone Gian Luca , Finocchi Cinzia , Gandolfo Carlo
Published: April 2003

Right-to-left shunt (RLS), usually due to patent foramen ovale, is a well-established risk factor for ischemic stroke in young patients, while the role of migraine as an independent factor is still debated. We evaluated 44 patients suffering from migraine with aura, and compared them with 73 patients younger than 50 with focal cerebral ischemia, and 50 controls, asymptomatic for cerebrovascular disease, and without a history of migraine. All the subjects underwent bilateral transcranial Doppler with injection of contrast medium in an antecubital vein. The test was performed during normal ventilation and during Valsalva maneuver, recording both the middle cerebral arteries and the basilar artery. Criteria for diagnosing RLS was the presence of at least 3 microbubbles within 15 s from injection. Eighteen out of 44 migraine patients (41%) showed RLS, as opposed to 8 of 50 controls (16%) (p < 0.005). Twenty-six out of 73 patients with cerebral ischemia had RLS (35%). We conclude that the prevalence of RLS in patients with migraine with aura is significantly higher than in normal controls, and is similar to the prevalence of RLS in young patients with stroke. These findings could be helpful in understanding the relationship between migraine and stroke.
The Risk of Intracerebral Haemorrhage with Smoking
Authors: Thrift Amanda G. , McNeil John J. , Donnan Geoffrey A. , for the Melbourne Risk Factor Study Group &
Published: April 2003

To determine whether smoking contributes to the risk of primary intracerebral haemorrhage (ICH) a case-control study was carried out on 331 consecutive cases of first-episode ICH as verified by computed tomography. Patients were age- and sex-matched to 331 community-based controls. Unlike other forms of stroke where smoking is an established risk factor, there was no increase in risk of ICH with smoking in this study (odds ratio, OR, 1.07, 95% confidence interval, CI, 0.63–1.81). Similar ratios were obtained for past and current smokers. Neither the amount smoked nor the duration of smoking were associated with ICH. Further investigation, however, revealed an interaction between smoking and hypertension on the risk of ICH that was similar regardless of the amount of cigarettes currently smoked and was largely seen to be a phenomenon in men (OR 8.13, 95% CI 2.04–32.42). This interaction is a new finding, but the post-hoc nature of this analysis requires that it be further tested, preferably in a large prospective study.
Cobalt-55 Positron Emission Tomography of Ipsilateral Thalamic and Crossed Cerebellar Hypometabolism after Supratentorial Ischaemic Stroke
Authors: De Reuck J. , Stevens H. , Jansen H. , Keppens J. , Strijckmans K. , Goethals P. , Lemahieu I. , Santens P. , Korf J.
Published: April 2003

Cobalt-55 (55Co) is a positron emission tomography (PET) tracer used to demonstrate brain damage, possibly associated to calcium-mediated processes. The degree of 55Co accumulation correlates with the severity of ischaemia in stroke patients. It is still a matter of debate whether ipsilateral thalamic hypometabolism (ITH) and crossed cerebellar hypometabolism (CCH), occurring after middle cerebral artery (MCA) infarcts, represent only a metabolic depression of these remote regions or can lead to structural damage. The present study investigates whether an increased 55Co influx can be demonstrated with PET in ITH and CCH after MCA infarcts. About half of the patients with ITH and CCH had a significant degree of 55Co uptake in, respectively, the ipsilateral thalamus and the contralateral cerebellar hemisphere. It was observed in patients with severe signs of stroke on admission and poor clinical outcome, and correlated well with the degree of 55Co influx within the supratentorial infarct. The present study demonstrates that ITH and CCH after MCA infarction can represent structural damage in these remote areas that occurs during the second week after stroke onset.
Percutaneous Endoscopic Gastrostomy after Acute Stroke:Complications and Outcome
Authors: Wijdicks Eelco F.M. , McMahon Molly M.
Published: April 2003

Objective: To review the complications and outcome of percutaneous endoscopic gastrostomy placement (PEG) in 74 patients with acute stroke. Patients and Methods: Medical record review and follow-up of patients with acute stroke admitted to a referral center. Results: There were no immediate procedure-related complications. Late complications included aspiration pneumonia (11%), PEG occlusion and replacement (6%), accidental PEG removal (6%), wound infection (3%) and fatal gastrointestinal bleeding in 1 patient. In 18 patients (28%), PEG could be subsequently removed due to improvement in swallowing. Conclusion: PEG provides an effective alternative method of enteral feeding, but its impact on outcome remains uncertain. Late complications occurred in one third of the patients, but were seldom life threatening. Removal of the gastrostomy tube and resumption of oral feeding was possible in more than a quarter of the patients. All our patients who received PEG placement after acute stroke remained severely disabled; one third of the patients died from systemic complications of their stroke.
Effects of Subcortical Cerebrovascular Lesions on Cortical Hemodynamic Parameters Assessed by Perfusion Magnetic Resonance Imaging
Authors: Nighoghossian N. , Berthezene Y. , Adeleine P. , Wiart M. , Damien J. , Derex L. , Itti R. , Froment J.C. , Trouillas P.
Published: April 2003

A simultaneous decrease of cerebral blood volume (CBV) and cerebral blood flow (CBF) has been described after subcortical stroke with positron emission tomography. However, this imaging modality cannot be applied routinely to stroke patients. Dynamic susceptibility contrast-enhanced MRI techniques (DSC-MRI) might be interesting in the assessment of these effects. Dynamic T2-weighted echo planar imaging was used to produce DSC-MR images during an intravenous bolus injection of gadopentetate dimeglumine in 9 patients who experienced a subcortical stroke involving thalamus or basal ganglia and in 8 control subjects. A series of 50 consecutive images at 1-second intervals was acquired at the anatomic level of the centrum semiovale quite distant from the subcortical lesion, rCBF and rCBV were determined over frontal and parietal regions of interest and through the entire cortical mantle. DSC-MRI enabled the detection of hemodynamic changes induced by subcortical stroke. Analysis of rCBV and rCBF values showed that the hemodynamic parameters were significantly decreased on the affected side. In controls mean rCBF and rCBV values recorded over the whole cortical mantle of each hemisphere showed no significant interhemispheric asymmetry.
Families of Trials: The Answers to All Our Questions?
Authors: Dennis Martin , Wardlaw Joanna , Sandercock Peter , Signorini David , Warlow Charles
Published: April 2003

Many of the important clinical decisions we make on a daily basis in stroke medicine are not supported by adequate evidence. This leads to variations in practice. If practice influences outcome, this must be regarded as unacceptable since it implies that many patients are receiving sub-optimal treatment. Where the advantages of certain treatment policies over others are only moderate, large randomised clinical trials provide the most reliable evidence of effectiveness. However, only a tiny proportion of patients with stroke are randomised in trials. Instead, the majority are exposed to treatments allocated haphazardly, rather than randomly, which serves only to delay the emergence of evidence concerning the relative merits of alternative treatment approaches. We suggest that we might increase the proportion of patients who contribute to advancing our knowledge by developing ‘families’ of trials. A ‘family’ would comprise a series of randomised trials into which patients with stroke may be enrolled either simultaneously or sequentially into one or more of the trials which would share common systems for randomisation and follow-up. Such a system would facilitate large, simple, randomised trials, reduce research costs, increase the generalisability of trial results and allow clinicians and patients to contribute to advancing our knowledge whenever they are uncertain about the best treatment. In this article, we discuss the advantages of this approach, some of the problems and their potential solutions.
Stroke during Sleep: Epidemiological and Clinical Features
Authors: Bornstein Natan M. , Gur Alexander Y. , Fainstein Pinchas Fainshtein , Korczyn Amos D.
Published: April 2003

Stroke during sleep is an unexplored area of vascular neurology and its pathogenesis; clinical significance and prevention still remain uncertain. The aim of our study was to determine the epidemiological and clinical patterns of ischemic stroke occurring during sleep. Consecutive patients (n = 1822) with acute ischemic stroke recorded in the Tel Aviv Stroke Register were studied. Stroke during sleep was determined whenever focal neurological deficit was verified to have occurred while the patient had been asleep. The comparisons between patients with stroke during sleep and while awake were performed using the t test with Bonferroni correction and the χ2 test for age, sex, vascular risk factors (i.e. ischemic heart disease, myocardial infarction, atrial fibrillation, arterial hypertension, hyperlipidemia, diabetes mellitus, peripheral vascular disease, smoking), vascular distribution (carotid versus vertebrobasilar) and severity of stroke (mild, moderate or severe). Data regarding the onset of stroke (during sleep or while awake) were available for 1,671 patients. A minority of strokes occurred during sleep (n = 311, 18.6%), and stroke during sleep was severer (χ2 = 11.9, p < 0.002). No significant differences were found in terms of age, sex and vascular distribution between the two groups. None of the vascular risk factors was found to be more frequent in stroke during sleep. Strokes occurring during sleep were found to be severer than those with onset while awake. However, no specific clinical patterns of risk factor profiles could be identified in these patients. Hemodynamic factors may play an important role in the occurrence of stroke during sleep, and this issue should be further investigated.