bluuebunny/crossref_metadata_2025 huggingface dataset:
The Influence of Hypoalbuminemia on Maximal Flow Rates and Transmembrane Pressure during Plasmapheresis – An in vitro Study
Authors: Unger J.K. , Horn N.A. , Kashefi A. , Blumberg A. , Klosterhalfen B. , Rossaint R.
Published: April 2003

Background: Plasmapheresis has been used for the treatment of acute liver failure (ALF). In these patients, hypoalbuminemia is often observed. Since albumin improves the disaggregability of erythrocytes, hypoalbuminemia might deteriorate rheology and thus influence the overall performance of plasmapheresis. Methods: Hypoalbuminemia was mimicked by using porcine blood because of its physiologically low albumin/globulin ratio (AGR). Filters (n = 16) were integrated in a closed extracorporeal in vitro system. In the control group (n = 8), native porcine blood (AGR 0.8) was used. In the study group (n = 8), we used porcine blood supplemented with human albumin to obtain the human AGR value of 1.2. Two different heparinization protocols were compared in each group (2.5 IU/ml: n = 4 with albumin and n = 4 without albumin versus 5 IU/ml: n = 4 with and n = 4 without albumin). Results: In both heparinization protocols the higher AGR led to lower transmembrane pressure (TMP) levels compared to the lower AGR. The reduced TMPs enabled higher blood flow and filtration rates. Conclusion: Maintenance of a physiological AGR in ALF patients might improve the performance of plasmapheresis and – as opposed to raised heparinization – contribute to a safer application.
Continuous Flow Peritoneal Dialysis: Clinical Applications
Authors: Diaz-Buxo José A.
Published: April 2003

Continuous flow peritoneal dialysis (CFPD) can be considered a special form of hemodialysis, during which peritoneal effluent, rather than blood, is being dialyzed using standard hemodialysis technology. Preliminary clinical data have identified poor mixing of the dialysis solution, streaming and recirculation as a significant limitation in achieving maximal solute removal and ultrafiltration. Better catheter designs remain a research priority in this field. Although the clinical experience is limited to short-lasting experiments with CFPD, the preliminary data strongly support the superiority of CFPD as the most effective peritoneal dialysis modality in removing small solutes and providing high ultrafiltration rates. The levels of clearance attained are similar to quotidian hemodialysis. In addition, it is expected that the current methodology will provide a new standard of solution biocompatibility.
Xenotransplantation in the 21st Century
Authors: Perico Norberto , Benigni Ariela , Remuzzi Giuseppe
Published: April 2003

Xenotransplantation, i.e. transplantation across species, is increasingly being viewed a potential solution to the problem of severe shortage of transplant donors. Clinical application of xenotransplantation is, however, limited in large part by the pre-eminent hurdle of the immune response of the recipient against the graft. This immunologic reaction is mediated initially by natural xenoreactive antibodies, complement and natural killer cells, and later by elicited humoral and cellular immune responses that ultimately lead to graft failure. Progress in understanding the cellular and molecular basis of xenograft rejection has characterized the past few years. Additional hurdles to xenotransplantation include physiologic incompatibility of the transplant and the risk of infections. The recent development of novel strategies to overcome xenograft rejection has brought about great optimism that xenotransplantation may be attainable in the near future.
Bioartificial Kidney Alters Cytokine Response and Hemodynamics in Endotoxin-Challenged Uremic Animals
Authors: Fissell William H. , Dyke D. Brad , Weitzel William F. , Buffington Deborah A. , Westover Angela J. , MacKay Sherrill M. , Gutierrez Jorge M. , Humes H. David
Published: April 2003

The mortality from sepsis complicated by renal failure remains extremely high despite the application of modern renal replacement therapy. This study investigated whether treatment with a bioartificial kidney consisting of a hemofilter in a continuous venovenous hemofiltration circuit (CVVH) with a cartridge containing renal proximal tubule cells, also called the Renal Tubule Assist Device (RAD), would alter the course of sepsis in an animal model. The RAD has been previously characterized in vitro and ex vivo and provides transport, metabolic and endocrine activity. Mongrel dogs (n = 10) underwent surgical nephrectomy and 48 h later were treated with CVVH and either a RAD containing cells (n = 5) or an identically prepared sham cartridge (n = 5). After 4 h of therapy, intravenous endotoxin 2 mg/kg was infused over 1 h to simulate gram-negative septic shock. Data on blood pressure, cardiac output and systemic markers of inflammation were collected. Mean peak levels of an anti- inflammatory cytokine, IL-10, were significantly higher in cell-treated animals (15.25 vs. 6.29 ng/ml; p = 0.037), and mean arterial pressures were higher in cell-treated versus sham-treated animals (p < 0.04). We have demonstrated that treatment of an animal model of endotoxin shock and renal failure with a bioartificial kidney has measurable effects on circulating mediators of inflammation and on hemodynamic stability of the challenged animal.
Hepatitis C: Who Should You Treat and How?
Authors: Sánchez Tapias José M. , Rodés Juan
Published: April 2003

At present the treatment of hepatitis C virus infection (HCV) has improved because of combined treatment with interferon (IFN) and ribavirin. The association of these two drugs has obtained a positive response in 40–50% of naive patients treated. Patients with relapse after monotherapy with IFN also show positive response with combined treatment in up to about 50% of patients with HCV genotype 1b. In patients with other genotypes the response is higher (up to 70%). In nonresponders to IFN alone, the response to combined therapy was higher although there is scarce data reporting this. Similar results were achieved in cirrhotic patients. The use of pegylated IFN has shown even greater efficacy. Sustained response was greater than 50%. Lastly, triple therapy with IFN, ribavirin and amantadine has been studied in small clinical trials in nonresponders to IFN monotherapy, with controversial results since in some studies sustained response was up to 48% being less than 20% in other studies.
Membrane Flux Not Biocompatibility Determines Beta-2-Microglobulin Levels in Hemodialysis Patients
Authors: Pickett Thomas M. , Cruickshank Alastair , Greenwood Roger N. , Taube David , Davenport Andrew , Farrington Ken
Published: April 2003

Background: Serum β2-microglobulin (β2M) levels are important in dialysis-related amyloid deposition but can be influenced by dialysis technique. Methods: We measured β2M levels in 3 centres using different dialysis regimes. Centre 1 (73 patients) used high-flux biocompatible, centre 2 (72 patients) low-flux biocompatible and centre 3 (142 patients) cuprophane dialysers. Results: β2M levels were lower with high-flux biocompatible than with low-flux biocompatible or cuprophane dialysis (22.3 ± 5.4 vs. 43.4 ±13.7 and 37.6 ±13.1 mg/l, respectively; p < 0.001). Levels were higher with low-flux biocompatible than with cuprophane dialysis (p < 0.001), but not if patients dialysed over 10 years were excluded. With low-flux biocompatible (47.4 ± 9.8 vs. 38.7 ± 15.2 mg/l; p < 0.01) and cuprophane dialysis (43.4 ± 8.2 vs. 36.7 ± 13.0 mg/l; p < 0.02), β2M levels were higher in patients dialysed over 5 years than in those dialysed less. Despite β2M levels increasing as residual renal function declined, there was no similar rise with high-flux biocompatible dialysis. Conclusions: Techniques allowing significant convection maintain lower β2M levels over many years. Membrane flux, not biocompatibility, is the main determinant of β2M levels in routine practice.
Fluid Resuscitation: Colloids vs. Crystalloids
Authors: Bellomo Rinaldo
Published: April 2003

The administration of intravenous fluids is perhaps the most common treatment given in the intensive care unit. According to biologic rationale, ongoing fluid losses should be replaced to maintain fluid homeostasis and relative or absolute deficiencies in circulating blood volume should be prevented or rapidly corrected. There is agreement that insensible fluid losses and isotonic fluid losses should be replaced with a judicious mixture of water and crystalloid solutions. There is, however, a great deal of controversy on which fluids should be used during the acute resuscitation phase to deal with acute relative or absolute hypovolemia. In particular, there is much controversy on whether colloidal or crystalloid solutions should be used. The controversy remains despite multiple meta-analyses. There are suggestions that albumin might increase mortality but the data supporting these concerns are weak. Starch solutions might adversely affect renal function. Crystalloids might be favored in trauma patients. These views remain inadequately supported by evidence. A randomized controlled trial now under way should increase the evidence base for practice in this area.
Keeping Pace with Changes in Technology and Technique
Authors: Baldwin Ian
Published: April 2003

The rapidly changing nature of new technologies and techniques in acute health care means it can be difficult keeping pace. Most facilities, large or small, are usually in continuous evaluation of a new technology. Published reviews and professional group guidelines can assist the process of change for continuous renal replacement therapy (CRRT) technologies and techniques. The current techniques and technologies are a mixed application of old and new technologies providing a combination of convective and diffusive solute clearance methods. There are a variety of anticoagulation approaches. New, purpose-built CRRT machines offer many advantages over old technology but their costs can be prohibitive and users do not always meet them with rapid behavioral change. Reading journal publications and texts, scientific meetings, education and training, Internet web site review/participation, quality improvement activities and an accurate local data base are the keys to keeping pace with changes and identifying whether a benefit can be anticipated and demonstrated. Possible changes for the future of techniques and technologies may be in the areas of modified approaches to continuous therapy with tailored approaches for specific patient care settings. Improved membrane characteristics for wider indications and the bio-artificial kidney are emerging along with blood pump and circuit design improvements, with new machine/operator interfaces.
Investigation of Lung Disease in Preterm Infants Using Magnetic Resonance Imaging
Authors: Adams Eleri W. , Counsell Serena J. , Hajnal Joseph V. , Allsop Joanna M. , Herlihy Amy , Edwards A. David
Published: April 2003

Many preterm infants require ongoing respiratory support despite treatment with exogenous surfactant. The reasons for this are unclear, but may involve one or a combination of changes in water content or distribution within the lung. Detailed three-dimensional information with the potential to provide quantitation of water content may help to investigate this further. We aimed to determine if magnetic resonance (MR) imaging could be developed to study lung disease in preterm infants. Appropriate MR sequences and procedures were defined and we found that T1 and proton density weighted images could be successfully acquired. The images contained three-dimensional information that could not be obtained using chest radiograph. MR imaging may be a useful method for studying the pathology of respiratory distress syndrome and chronic lung disease in preterm infants.
The Antennal Lobe of Orthoptera – Anatomy and Evolution
Authors: Ignell Rickard , Anton Sylvia , Hansson Bill S.
Published: April 2003

The first odor-processing neuropils of insects comprise glomeruli, islets of neuropil, that are supplied by olfactory receptor neurons and give rise to efferent axons to higher brain centers. Glomeruli size and organization varies in a taxon-specific manner across the Insecta, suggesting possible correlates between their organization and chemosensory behaviors in different insect groups. Comparative studies of antennal lobe glomeruli within the Orthoptera have been used to infer how the various taxon-specific arrangements of odorant-processing structures (glomeruli) might have evolved. The cellular arrangements in glomeruli have been surveyed using anterograde filling and Golgi impregnation of antennal receptor neurons projecting to the antennal lobe in Stenopelmatidae, Tettigoniidae, Gryllidae, Tetrigidae and Acrididae. These taxa, which represent the two sub-orders of Orthoptera, reveal a high correlation between the neural architecture of the glomeruli and structures within the glomeruli. Using a recent molecular phylogeny of the Orthoptera we have mapped the occurrence of glomerular characteristics to infer the evolution of antennal lobe structures in orthopterans. The functional implications of these results are discussed.
Localization of FMRFamide-Like Immunoreactivity in the Brain of the Viviparous Skink (Chalcides chalcides)
Authors: D’Aniello Biagio , Fiorentin Maria , Pinelli Claudia , Guarino Fabio M. , Angelini Francesco , Rastogi Rakesh K.
Published: April 2003

Neuroanatomical distribution of FMRFamide-like immunoreactivity was investigated in the brain and olfactory system of the viviparous skink, Chalcides chalcides. In the adult brain FMRFamide immunoreactive (ir) perikarya were observed in the diagonal band of Broca, medial septal nucleus, accumbens nucleus, bed nucleus of the anterior commissure, periventricular hypothalamic nucleus, lateral forebrain bundle, and lateral preoptic, subcommissural, suprachiasmatic and lateral hypothalamic areas. This pattern was seen in both male and female brains. Though all major brain areas showed FMRFamide-ir innervation, the densest ir fiber network was observed in the hypothalamus. During development, ir elements were observed for the first time in embryos at mid-pregnancy. FMRFamide perikarya were located along the ventral surface of the vomeronasal nerve, in the olfactory peduncle mediobasally, as well as in the anterior olfactory nucleus and olfactory tubercle. Furthermore, some ir neurons were observed in the rhombencephalic reticular substance; however, the ir fiber network was poorly developed. Later in development FMRFamide-ir neurons appeared also in the bed nucleus of the anterior commissure as well as the rhombencephalic nucleus of solitary tract and the dorsal motor nucleus of vagus nerve. In juveniles, the distribution profile of FMRFamide immunoreactivity was substantially similar to that of the adults, with a less widespread neuronal distribution and a more developed fiber network. Ontogenetic presence of FMRFamide immunoreactivity in the nasal area has been linked to the presence of a nervus terminalis in this reptile.
A Comparative Analysis of Relative Brain Size in Waterfowl (Anseriformes)
Authors: Iwaniuk Andrew N. , Nelson John E.
Published: April 2003

Variation in relative brain size was examined in 55 species of waterfowl (Anseriformes). Using both conventional statistics and phylogenetically based comparative methods, the extent of variation in relative brain size and possible relationships with mode of foraging and diet were examined. The results indicate that although brain size does vary considerably between closely related species of waterfowl, it is not reliably related to either foraging mode or diet. There are a number of possible reasons for the lack of relationships between brain size and foraging mode and diet. Firstly, subtle changes in foraging mode and diet may favor relatively large changes in brain size. Secondly, foraging mode and diet could be correlated with the expansion of an individual brain region without affecting overall brain size. Thirdly, other behavioral/ecological traits may be more important with respect to brain size evolution in waterfowl. For example, the relatively large brain of the musk duck (Biziura lobata) and altriciality of their young in comparison to other stiff-tailed ducks (Oxyura spp.) indicates that developmental rate plays a significant role in the evolution of brain size. Given the difference between our results and that reported in inter-order comparisons of brain size in birds, further research is required into other avian orders to assess how brain size and behavior might be related within orders as well as between them.
Correlation between the Admission Electrocardiogram and Regional Wall Motion Abnormalities As Detected by Echocardiography in Anterior Acute Myocardial Infarction
Authors: Porter Avital , Wyshelesky Albert , Strasberg Boris , Vaturi Mordehai , Solodky Alejandro , Imbar Shula , Sagie Alex , Battler Alexander , Birnbaum Yochai
Published: April 2003

We correlated ST elevation in various leads on admission and regional dysfunction in 132 patient with first anterior acute myocardial infarction using echocardiography. ST elevation in leads I and a VL and II, III and aVF was not associated with a specific pattern of regional dysfunction. Basal anterior and septal regional dysfunction were seen more often in patients with ST elevation in V1 (49 vs. 25%, p = 0.006; 35 vs. 17%, p = 0.048, respectively). Patients with ST elevation in V2 had more regional dysfunction of the apical inferior region (84 vs. 53%; p = 0.01). ST elevation in V5 and V6 was not associated with more apical or lateral wall motion abnormalities. ST elevation in lead V1 in anterior myocardial infarction is associated with a high incidence of regional dysfunction of the basal anterior, anteroseptal and septal regions.
A Technical Approach for Optimizing Surveillance of Patients with Unstable Coronary Syndromes: Continuous Vectorcardiography Ischemic Monitoring
Authors: Nørgaard Bjarne Linde , Thygesen Kristian , Gill Sabine , Dellborg Mikael
Published: April 2003

Continuous vectorcardiography ischemic monitoring (VCG) is a noninvasive technique which has contributed much to our understanding of the dynamics of acute coronary syndromes. For risk assessment of patients with unstable angina pectoris or non-Q-wave myocardial infarction, VCG shows important prognostic power which is further enhanced by its combination with the measurement of highly sensitive and specific biochemical markers of myocardial injury. VCG surveillance after revascularization therapy of Q-wave myocardial infarction is widely accepted because of its potential of assessing vessel patency, of estimating infarct size, and of revealing residual myocardial ischemia. Valuable prognostic information is available in real time with VCG, and treatment strategies may be based upon more reliable grounds. In this survey, the VCG technique is presented together with the most frequently used vectorcardiographic variables. Further, the use of the method for risk stratification of patients with unstable coronary syndromes is also described.
Is the Morning Peak of Acute Myocardial Infarction’s Onset Due to Sleep-Related Breathing Disorders?
Authors: Aboyans Victor , Cassat Claude , Lacroix Philippe , Tapie Philippe , Tabaraud François , Pesteil Francis , Bertin François , Laskar Marc , Virot Patrice
Published: April 2003

Many studies have shown that the risk of experiencing a myocardial infarction (MI) is increased during the first hours of the morning. Sleep apnea syndrome (SAS) is associated with an enhanced adrenergic activity, prolonged a few hours after awakening. We aimed at assessing whether sleep breathing disorders could be a culprit for the morning excess rate of MI. We studied 40 middle-aged men admitted for an acute MI. An overnight polysomnographic study was performed 37.4 ± 9.4 days after the MI. The prevalence of SAS was high (30%). The prevalence of SAS was significantly higher in patients with the MI onset during the morning. The circadian pattern was significantly different in patients with or without SAS: those with SAS presented an important peak of MI onset during the period between 06.00 and 11.59 h. None of them had their MI during the period between 24.00 and 05.59 h. This different nyctohemeral pattern underlines the potential role of sleep breathing disorders as a trigger of MI.
Prevalence of Heart Disease in Asymptomatic Chronic Cocaine Users
Authors: Roldan Carlos A. , Aliabadi Darius , Crawford Michael H.
Published: April 2003

To determine the prevalence of heart disease in outpatient young asymptomatic chronic cocaine users, 35 cocaine users and 32 age-matched controls underwent resting and exercise electrocardiography (ECG) and Doppler echocardiography. Findings consistent with coronary artery disease were detected in 12 (34%) patients and 3 (9%) controls (p = 0.01). Decreased left ventricular systolic function was demonstrated in 5 (14%) patients, but in none of the controls (p = 0.055). Finally, resting and peak exercise abnormal left ventricular filling was detected in 38 and 35% of patients as compared to 19 and 9% of controls, respectively (p = 0.11 and 0.02, respectively). We conclude that coronary artery or myocardial disease is common (38%) in young asymptomatic chronic cocaine users. Therefore, screening ECG and echocardiography may be warranted in these patients.
Arrhythmias in Neurofibromatosis
Authors: Verma Sumit , Ahmed Shilpi , Gudapati Surendra B. , King Don W. , Meador Kimford J. , Ahmed Rafique
Published: April 2003

Patients with neurofibromatosis have a higher incidence of anatomic cardiac abnormalities. However, there is little data regarding incidence of arrhythmias in this population. It is known that these patients have a higher mortality than the normal population, and it is possible that some deaths may be due to preventable causes such as cardiac arrhythmias. We report a patient with neurofibromatosis who was treated for a refractory seizure disorder for 8 years. However, video/EEG monitoring demonstrated that the patient had recurrent syncopal seizures secondary to sinus node dysfunction. Complete resolution of symptoms occurred after a permanent pacemaker implantation. We believe this is the first reported case of sinus node dysfunction associated with neurofibromatosis.
Clopidogrel and Side Effects
Authors: Reichenberger F. , Wirtz H. , Paschke R.
Published: April 2003

Clopidogrel is a recently developed thrombocyte inhibitor with fewer side effects. We report 2 patients with purpura and thrombopenia, respectively, due to clopidogrel therapy. As this compound is widely used in clinical practice, the occurrence of hematological and dermal side effects should be considered.
Thyroid Hormone Substitution Therapy Rapidly Enhances Left-Ventricular Diastolic Function in Hypothyroid Patients
Authors: Virtanen V.K. , Saha H.H.T. , Groundstroem K.W.E. , Salmi J. , Pasternack A.I.
Published: April 2003

Objective: Alterations in thyroid status may lead to changes in both systolic and diastolic function of the heart. Pulsed Doppler echocardiography is a reliable non-invasive means of assessing left-ventricular (LV) diastolic function. The aim of the present study was to evaluate LV diastolic function in patients with primary hypothyroidism receiving thyroxine therapy. Methods: Twelve patients (all females, mean age 47 ± 17, range 16–69 years) with primary hypothyroidism were studied by pulsed Doppler echocardiography. The first examination was made before the start of thyroxine substitution and the second at 37–68 (mean 53 ± 10) days after commencing thyroxine treatment (mean dose 136 ± 22 µg/day). Results: During thyroxine substitution therapy, the hypothyroid patients became clinically euthyroid and serum T4 increased from 51 ± 21 to 119 ± 24 nmol/l; TSH decreased from 50.4 ± 55.3 to 1.2 ± 1.5 mU/l. During therapy, heart rate increased from 61 ± 8 to 68 ± 10 (p = 0.05). The LV posterior wall (7.8 ± 1.0 mm) and interventricular septum thickness (8.0 ± 1.4 mm) were significantly greater in hypothyroid patients than in the control subjects (6.4 ± 1.0 mm, p = 0.007 and 6.8 ± 1.0 mm, p = 0.04, respectively). There was no significant change in LV dimensions and wall thickness during follow-up. E/Amax increased significantly during treatment (from 1.679 ± 0.432 to 1.947 ± 0.335, p = 0.006). The isovolumic relaxation time shortened significantly (from 88 ± 23 ms to 75 ± 24 ms, p = 0.005). Conclusions: The present study shows that LV diastolic function as assessed by pulsed Doppler echocardiography in hypothyroid patients is enhanced by thyroxine therapy during a rather short follow-up period.
Peritoneal Ultrafiltration for Chronic Congestive Heart Failure: Rationale, Evidence and Future
Authors: Mehrotra Rajnish , Khanna Ramesh
Published: April 2003

Peritoneal dialysis (PD) was the first dialytic therapy used to achieve euvolemia in individuals with refractory congestive heart failure. PD remains a viable therapy for the short-term management of refractory congestive heart failure, and fluid removal rates comparable to those obtained with the continuous extracorporeal therapies can be achieved. However, with advances in extracorporeal therapies, the role of PD in these situations is limited to those individuals in whom vascular access cannot be obtained or if extracorporeal therapies are not available. On the other hand, PD is the ultrafiltration therapy of choice for the long-term ambulatory management of individuals with refractory congestive heart failure, either as a palliative therapy or as a bridge to definitive surgery or transplantation. A reduction in hospitalization rates and an improvement in functional capacity can be expected under such circumstances; however, survival is unlikely to be affected.
Plasma Levels of Brain Natriuretic Peptide Increase in Patients with Idiopathic Bilateral Atrial Dilatation
Authors: Arima Mizuhiro , Kanoh Tatsuji , Kawano Yasunobu , Oigawa Tetsuya , Yamagami Shinichiro , Matsuda Shigeru
Published: April 2003

Idiopathic bilateral atrial dilatation (IBAD) is an extremely rare anomaly and is usually associated with atrial fibrillation. Plasma levels of atrial natriuretic peptide (ANP) have been shown to increase in patients with atrial fibrillation. However, secretion of ANP and brain natriuretic peptide (BNP) in patients with IBAD remains unclear. We investigated the clinical features of 9 patients with IBAD and 16 age- and sex-matched patients with lone atrial fibrillation (LAF). Plasma levels of ANP and BNP were measured, and echocardiographic parameters were followed. Left (LAV) and right atrial volumes (RAV) were significantly higher in patients with IBAD than in patients with LAF (both p < 0.01). There were no differences between patients with IBAD and LAF in other echocardiographic parameters. The percent increases in LAV and RAV in patients with IBAD exceeded those in patients with LAF (both p < 0.01). Plasma levels of BNP and the BNP/ANP ratios in patients with IBAD were significantly higher than those in patients with LAF (both p < 0.01), but there was no significant difference in plasma levels of ANP. Regarding the clinical course of the patients with IBAD compared with those with LAF, the atrial volume increased gradually, and plasma levels of BNP were significantly higher. These findings suggested that IBAD was not only influenced by long-term atrial fibrillation, but also by subclinical left ventricular dysfunction.
Prevention by Means of Fluoride of Enamel Erosion as Caused by Soft Drinks and Orange Juice
Authors: Larsen M.J.
Published: April 2003

Fluoride has been suggested to prevent erosion of the teeth, either after a topical treatment of the teeth or by addition of fluoride to the acidic drink. The main aim of the present study was to describe the dissolution of calcium fluoride in some soft drinks and orange juice and compare it with the amounts of calcium fluoride left on the enamel surfaces after a topical treatment. A further aim was to describe the dissolution of enamel in soft drinks and juice saturated for 3 days with solid calcium fluoride. Solid calcium fluoride was suspended in each of 10 soft drinks and orange juices and gently agitated for 72 h, after which the drinks were analyzed for calcium, phosphate and fluoride and pH was determined. To examine the erosion–preventive effect of the calcium fluoride–rich drink, intact teeth were exposed to the drinks with or without calcium fluoride. It was found that from 6 to 45 mg of calcium fluoride was dissolved per liter of drink. The more acidic the drink, the more calcium fluoride was dissolved, presumably due to HF formation. The teeth exposed to the soft drinks all showed erosion–like lesions. Very little effect of the 4–6 ppm ionic fluoride dissolved in the soft drinks was observed. In orange juice, however, the dissolved calcium fluoride established a saturation with respect to fluorapatite and consequently, the erosion–like lesion was replaced by a caries–like lesion. In conclusion, the acidic soft drinks are capable of dissolving considerable amounts of calcium fluoride and the erosion–preventive effect of even high fluoride concentrations is limited.
Are More Complex Study Designs Needed for Future Acute Stroke Trials?
Authors: Mohr J.P. , Mast H. , Thompson J.L.P. , Sacco R.L.
Published: April 2003

Stroke scales were originally devised to quantify the disturbance in neurological function explained by a stroke-induced brain lesion [1]. Given the century-long experience with the clinical examination and the beliefs in the principles of clinicoanatomical correlation, most of the popular stroke scales were derived directly from the traditional neurological examination. Included in the assessment was, typically, a score to estimate the level of consciousness: uni- or bilateral disturbances in the main sensory and motor systems, and disturbances in so-called higher cerebral functions including speech, language, memory, the patient’s awareness of the extent of the neurological disturbance, and response to stimuli presented on one or other sides of space. Recognizable as the traditional examination, most such scales have been readily accepted by clinical investigators.
Advantages and Disadvantages of Neurological Scales
Authors: Orgogozo Jean-Marc
Published: April 2003

The neurological features demonstrated by a patient form a valid measurement for the level of impairment experienced following a stroke. These features can be assessed using neurological scores, which assign values to the many deficits exhibited by such patients and allow a prognosis to be made on patient outcome. Several stroke scales have been produced, most of which are based on normative scaling. While these stroke scales provide effective patient assessment, they do have some associated disadvantages. The analysis of multiple minor deficits can lead to the same scoring as a few major deficits, some scales assess stroke only on a small number of items. In addition, most scales operate best in the middle range of stroke severity and have limited value in mild and severe cases. Despite these drawbacks, neurological scores give an earlier and more sensitive response to the outcome of stroke than functional scales. They are powerful prognostic indicators in stroke. Most of them are equivalent, which allows comparison between studies.
Acute Stroke Subtypes – Is There a Need for Reclassification?
Authors: Hennerici M.G. , Schwartz A.
Published: April 2003

Although stroke covers a wide range of diseases and aetiologies, it is currently managed using uniform treatments, such as thrombolysis and neuroprotective drugs, irrespective of the individual stroke pathophysiology. The time-consuming, ineffective and often misleading standard work-up of stroke subtypes is now being augmented with immediate brain and vessel imaging studies and laboratory testing. This approach means that, in addition to distinguishing between haemorrhagic and ischaemic lesions, ischaemic lesions can be assigned to various stroke subtypes. Diffusion-weighted magnetic resonance imaging is useful to detect the cytotoxic oedema occurring early in cerebral ischaemia, and sequential studies are useful in evaluating each patient’s prognosis. Both this technique and magnetic resonance angiography are effective in the assessment of an optimal selection of therapy in early stroke. Particular benefit is derived by patients with recent infarction and overlapping signs and symptoms of residual and acute deficits, and those with more than one aetiology. Demonstration of very small versus large ischaemic territories supports the likelihood of a good spontaneous outcome and discourages high-risk treatment procedures. Chronic and acute lesions may be differentiated and potentially salvageable tissue identified in cases of embolic stroke. The micro-embolic nature of lesions formed by the fragmentation of more proximal intracranial artery occlusions may be revealed by ultrasound studies showing high-intensity transient signals. Results from such studies are also useful to re-evaluate present concepts of stroke subtypes: recent data suggest that the ‘border zone infarction’ concept needs to be largely abandoned.
One Year after CAPRIE, IST and ESPS 2
Authors: Hankey Graeme J.
Published: April 2003

The IST, CAPRIE and ESPS-2 have shown that large collaborative randomised trials can be conducted in stroke medicine and can provide statistically and clinically significant results. They, and other concurrent studies, have highlighted the potential hazards of early anticoagulation, and the effectiveness and safety of early (and continuous) antiplatelet therapy in limiting early stroke recurrence and its consequences. In addition, they have shown that antiplatelet agents with differing mechanisms of action can have different effects, and perhaps additive effects when combined. The ESPRIT trial should delineate the roles of oral anticoagulant therapy, and the combination of aspirin and dipyridamole, in the prevention of stroke due to arterial disease. Future trials will hopefully determine the role in secondary stroke prevention of inhibitors of the platelet GPIIb/IIIa complex (the final common pathway of platelet aggregation), the combination of anitplatelet agents with different mechanisms of action (e.g. aspirin and clopidogrel, aspirin and IIb/IIIa inhibitors), the combination of antiplatelet agents and oral anticoagulants (which may simultaneously modify platelet function and fibrin production), and the combination of antithrombotic and cholesterol-lowering (statin) medications.
New Genetic Concepts and Stroke Prevention
Authors: Auburger Georg
Published: April 2003

So far, stroke genetics has the reputation of daunting complexity and heterogeneity. However, progress through efforts at studying the human genome has provided novel technologies and focus, and 12 stroke genes or loci have already been identified in the last years, usually through the study of large pedigrees. However, particularly little is known about the ischemic form of stroke, and only recently could one chromosomal locus be shown to exert a major effect on stroke latency and outcome – through QTL studies in mouse strains. Whether the outstanding role of this one gene locus is also true in humans should be tested in linkage analyses of large pedigrees. The characterization of such families will probably be essential for progress in molecular genetics of ischemic stroke as well as being a challenge for clinical stroke centers.
Imaging Arterial Wall Disease
Authors: Hennerici Michael , Meairs Stephen
Published: April 2003

Ultrasonographic imaging of the carotid arteries allows assessment of both early and advanced atherosclerotic disease. This noninvasive technique has played a central role in many recent epidemiological studies and is being used increasingly for evaluating the efficacy of atherosclerosis prevention trials. New developments in ultrasound equipment, the use of echocontrast agents, novel applications of three- and four-dimensional sonography and in vivo characterization of plaque constituents with high-resolution MRI have broadened the scope of imaging of arterial walls, providing both enhanced information on disease progression as well as new insights into pathomechanisms of carotid plaque embolization. This article highlights pertinent issues of imaging of arterial wall disease and discusses important areas of current and future research in this field.
Cerebral Blood Flow, Glucose Metabolism and TUNEL-Positive Cells in the Development of Ischemia
Authors: Terada Koichi , Inao Suguru , Mizutani Nobuhiko , Tsukada Hideo , Yoshida Jun
Published: April 2003

Few in vivo studies were available about the relation between cerebral blood flow, glucose metabolism and the appearance of apoptotic cells in the development of cerebral infarct. To investigate this, we measured local cerebral blood flow (lCBF), local cerebral metabolic rate in glucose (lCMRglc), and histopathology in transient focal cerebral ischemia in the rat. A unilateral middle cerebral artery occlusion (MCAO) was induced for 2 h in Wistar-ST rats (n = 42). A histopathological study with hematoxylin-eosin staining and the TdT-mediated dUTP-biotin nick-end labeling (TUNEL) method was performed. lCBF was measured by means of the 14C-iodoantipyrine autoradiography technique during MCAO (n = 6), and 1, 22 and 70 h after reperfusion. lCMRglc was also measured by autoradiography with 14C-2-deoxyglucose in the animals 22 h after reperfusion. These parameters were assessed in each region of interest: the ischemic core, boundary zones (BZ-I and BZ-II) and remote area. The boundary zones were defined as the area based on TUNEL positivity (more than 5/field) at 22 h after reperfusion (BZ-I) and at 70 h after reperfusion (BZ-II). In the BZ-I, lCBF was decreased to 18% of the control during MCAO, and lCBF and lCMRglc showed 44 and 62% of the control, respectively, 22 h after reperfusion. In this area, TUNEL-positive cells increased at 22 h, then markedly decreased 70 h after reperfusion. In the BZ-II, lCBF decreased to 39% of the control during MCAO, then returned to about 90% of the control 22 h after reperfusion. lCMRglc was maintained near its normal range (82% of the control) 22 h after reperfusion. Histopathology of BZ-II was normal 22 h after reperfusion. The TUNEL positivity of neurons in our study was assumed to be a marker of apoptotic cells. Our data suggested that the apoptotic process plays an important role in the maturation of a cerebral infarct. Both lCBF and lCMRglc were maintained with only a mild reduction in the predisposing phase of apoptosis, suggesting that sufficient blood supply and glucose metabolism are required to promote the process of apoptosis.
Recurrence of a Cerebral Arteriovenous Malformation after Surgical Excision
Authors: Freudenstein Dirk , Duffner Frank , Ernemann Ulrike , Rachinger Jens , Grote Ernst H.
Published: April 2003

Complete resection of a cerebral arteriovenous malformation (AVM) should eliminate the future risk of an associated intracranial bleeding. Because total removal of an AVM may be difficult to assess at the time of surgery, postoperative angiography has become the accepted standard for documenting that complete removal has been achieved. However, even angiographically confirmed excision of an AVM does not completely exclude the possibility of rebleeding. Regrowth of an AVM with subsequent haemorrhage has been documented in children and is attributed to forces acting on the immature vasculature. The authors report the case of a 21-year-old man whose AVM recurred 5 years after angiographically proven complete excision. According to the presented case, the authors emphasise that, even in adults, angiographic documentation of total removal does not always eliminate the risk of reformation of an AVM.
Cerebral Vein and Dural Sinus Thrombosis in Portugal: 1980–1998
Authors: Ferro José M. , Correia Manuel , Pontes Celso , Baptista Miguel V. , Pita Fernando
Published: April 2003

There is insufficient information on the prognosis and safety of anticoagulation in acute cerebral vein and dural sinus thrombosis (CVDST). To describe the clinical aspects and medical management of CVDST in Portuguese hospitals, to evaluate the safety of anticoagulation in this setting, and to identify subgroups of CVDST patients with different prognoses, we registered symptomatic CVDST patients admitted to Portuguese hospitals since 1980. Cases were collected from file review up to 6/95 and from consecutively admitted patients from 6/95 to 6/98. One hundred and forty-two patients were included from 20 centers (51 retrospectively and 91 prospectively). One hundred and twelve patients (79%) were anticoagulated. There were only 6 new intracranial hemorrhages (4 in anticoagulated patients) and 2 systemic hemorrhages. Nine (6%) patients died. At discharge, 96 (68%), had recovered completely and only 6 (4%) were dependent (Rankin ≧3). Significant multivariate predictors of death/dependency were central nervous system infection as a predisposing cause (odds ratio, OR = 15.4; 95% confidence interval CI = 111–1.1), encephalopathy on admission (OR = 5.2; 95% CI = 18.7–1.5) and hemorrhage on admission CT/MR (OR = 3.6; 95% CI = 12.9–1). Significant predictors of complete recovery were no encephalopathy on admission (OR = 5; 95% CI = 12.5–2.1), age <45 years (OR = 3.8; 95% CI = 9.2–1.6) and anticoagulation (OR = 3.8; 95% CI = 9.6–1.5). It is possible to identify CVDST patients with potential bad or good prognosis in the acute phase. Anticoagulation was safe and a predictor of complete recovery in acute CVDST.
Acute Phase Predictors of Subsequent Psychosocial Burden in Carers of Elderly Stroke Patients
Authors: Thommessen B. , Wyller T.B. , Bautz-Holter E. , Laake K.
Published: April 2003

The objective was to describe the psychosocial burden experienced by informal carers of elderly stroke victims, and to identify its predictors among baseline characteristics of the patients. From a prospective study of 171 elderly stroke patients admitted to a geriatric ward for rehabilitation in the acute phase, 68 patients living at home with a primary caregiver were identified 6 months after the stroke. At baseline, all the patients were assessed with respect to motor function, cognitive function, global handicap and activities of daily living, and after 6 months the caregivers were assessed, using the Relatives’ Stress Scale. According to this, the most frequent impacts were worries that an accident might befall their relatives, that they had to reorganise their household routines and further, that their social life and ability to take holidays had been reduced. Impaired cognitive function was the only baseline patient characteristic that predicted a subsequent psychosocial burden on the carer. Special attention should be paid to elderly stroke patients initially assessed with impaired cognitive function and their caregivers.
Carbon Disulfide Vasculopathy: A Small Vessel Disease
Authors: Huang Chin-Chang , Chu Chun-Che , Chu Nai-Shin , Wu Trong-Neng
Published: April 2003

We present the clinical manifestations of 4 male patients with acute stroke-like symptoms and polyneuropathy after long-term exposure to carbon disulfide (CS2) in a viscose rayon plant. The ages of onset of polyneuropathy ranged from 42 to 45 years with a duration of CS2 exposure between 6 and 21 years. The ages of onset of stroke were from 42 to 48 years. The risk factors for stroke including heart disease and diabetes were denied, except for smoking in 4, hyperlipidemia in 2 and hypertension in 1. At the initial visit in 1992, only 2 patients developed sudden onset of hemiparesis suggesting a lacunar stroke before the diagnosis of CS2 intoxication. Brain computed tomography (CT) scans showed low-density lesions in the basal ganglia in 2 patients, cortical atrophy in 1 and normal in 1. Brain magnetic resonance image (MRI) study disclosed multiple lesions in the corona radiata and basal ganglia on T2-weighted images in 3 patients and cortical atrophy in 1. After the diagnosis, they left their jobs for a CS2-free environment, and improvement of the working conditions was noted. During 5 years follow-up period, another 2 patients also developed an acute episode of stroke with hemiparesis. Brain CT and/or MRI follow-up studies in these 2 patients revealed new lesions in the basal ganglia and corona radiata. Intriguingly, a patient with previous stroke also developed new lesions in the bilateral thalami and brainstem. Carotid Doppler scan, transcranial Doppler scan and/or cerebral angiography did not show any prominent stenosis or occlusion in the major intracranial large arteries. We conclude that encephalopathy may occur in patients after long-term CS2 exposure, probably due to impaired cerebral perfusion. The lesions tend to occur in the basal ganglia, corona radiata and even brainstem, particularly involving the small-sized vessels. In addition, the cerebral lesions may progress even after cessation of CS2 exposure. Therefore, we suggest that CS2 exposure may be a risk factor for stroke.
The Effect of Transdermal Glyceryl Trinitrate, a Nitric Oxide Donor, on Blood Pressure and Platelet Function in Acute Stroke
Authors: Bath Philip M.W. , Pathansali Rohan , Iddenden Robert , Bath Fiona J.
Published: April 2003

Background and Purpose: Hypertension is a common medical complication in acute stroke and is associated with a poor outcome. However, no large trials have assessed the effect of lowering blood pressure (BP) on outcome, and it remains unclear how BP should be managed in acute stroke. We assessed, in a double-blind randomised controlled trial, whether the nitric oxide (NO) donor glyceryl trinitrate (GTN, a known systemic and cerebral vasodilator), would lower BP and alter platelet function. Methods: Thirty-seven patients with recent (<5 days) ischaemic or haemorrhagic stroke were randomised by minimisation to 12 days of daily treatment with transdermal GTN or matching placebo patches. Twenty-four-hour ambulatory BP was measured before and during GTN treatment at days 0, 1 and 8. Platelet aggregation and expression of adhesion molecules were assessed at the same time points. Functional outcome (Rankin scale) and case fatality were assessed at 3 months. Analysis was by intention-to-treat. Results: GTN significantly lowered BP by 13.0/5.2 mm Hg at day 1 and 9.3/5.0 mm Hg at day 8. The lesser reduction at day 8 than day 1 suggests that tolerance to GTN was developing. Non-significant falls of 0.9/0.6 and 3.8/0.0 mm Hg occurred at days 1 and 8, respectively, in the placebo group. GTN had no effect on heart rate, or platelet aggregation or expression of platelet adhesion molecules, including glycoproteins Ia, Ib, IIIa and P-selectin. Additionally, GTN did not alter case fatality or dependency, although the study was not powered for these outcomes. Conclusions: Transdermal GTN, an NO donor, lowered BP by 5–8%, a clinically significant and relevant, but not excessive, degree in patients with acute stroke. However, GTN had no effect on platelet aggregation or expression of adhesion molecules. Since NO donors increase cerebral blood flow in patients with acute ischaemic stroke, GTN may be an appropriate drug for testing the effect of lowering BP on functional outcome.
Platelet Glycoprotein IIb/IIIa Blockade in Acute Ischemic Stroke
Authors: Bogousslavsky Julien , Leclerc Jacques R.
Published: April 2003

While thrombolytic therapy is approved in the United States and Canada for treatment of acute ischemic stroke, only a small number of patients are currently treated. Additional agents that could restore or improve cerebral flow are needed. Based on the experience in acute coronary syndromes, reperfusion agents such as platelet glycoprotein IIb/IIIa antagonists, alone or in combination with reduced doses of thrombolytic agents, have the potential for improving the safety and efficacy of recombinant tissue plasminogen activator (rt-PA). In addition, these newer agents may permit extension beyond the current 3-hour window from symptom onset used for systemic rt-PA.