bluuebunny/crossref_metadata_2025 huggingface dataset:
Ebselen in Acute Middle Cerebral Artery Occlusion: A Placebo-Controlled, Double-Blind Clinical Trial
Authors: Ogawa Akira , Yoshimoto Takashi , Kikuchi Haruhiko , Sano Keiji , Saito Isamu , Yamaguchi Takenori , Yasuhara Hajime , for the Ebselen Study Group &
Published: April 2003

A randomized, double-blind, placebo-controlled trial of ebselen was conducted in patients with complete occlusion of the middle cerebral artery. Ebselen or placebo granules suspended in water (150 mg b.i.d.) were orally administered within 12 h of onset and continued for 2 weeks. The major end points were the maximum volume of cerebral infarct measured on follow-up computed tomography and the Glasgow Outcome Scale score at 1 month. One hundred and five patients were enrolled in this trial. Although the intent-to-treat analysis of 99 patients (43 given ebselen and 56 given placebo) did not reach statistical significance in reduction of the infarct volume (p = 0.099), the protocol-compatible analysis of 83 patients with complete occlusion of the middle cerebral artery (34 given ebselen and 49 given placebo) determined a significant reduction using ebselen treatment (p = 0.034). A good outcome was seen in approximately 15% more patients from the ebselen group, but the difference between the 2 groups was not significant (p = 0.129). There was a corresponding significant reduction in the volume of cerebral infarct and an improvement in the outcome of patients who started treatment within 6 h of onset. These findings may suggest that ebselen protected the brain from ischemic damage in the acute stage.
Subarachnoid Hemorrhage due to Septic Embolic Infarction in Infective Endocarditis
Authors: Krapf Hilmar , Skalej Martin , Voigt Karsten
Published: April 2003

During antibiotic therapy, a 56-year-old man with a Streptococcus bovis endocarditis developed an infarction of the right middle cerebral artery (MCA). Thirty hours after stroke onset, cranial computed tomography controls demonstrated a secondary subarachnoid hemorrhage, marked in the cistern of the right MCA. The latent period, cerebrospinal fluid analysis, angiographic and pathologic findings favor the assumption of a pyogenic arterial wall necrosis of the MCA due to a septic embolus. This pathomechanism of intracranial hemorrhage in infective endocarditis should be distinguished from a rupture of a mycotic aneurysm.
Cerebral Microembolus Generation in Different Extracorporeal Circulation Systems
Authors: Müllges Wolfgang , Berg Daniela , Babin-Ebell Jörg Babin-Ebell , Toyka Klaus V. , Elert Olaf
Published: April 2003

Microemboli generated during extracorporeal circulation (ECC) are likely to induce neurological sequelae. This study examines whether the choice of a distinct type of ECC can reduce intracerebral emboli counts. Middle cerebral artery blood flow during coronary artery bypass grafting was monitored continuously by transcranial Doppler ultrasound in 45 patients. The ECC systems used were a roller pump (n = 16), a centrifugal pump (n = 18) and a combination of centrifugal pump and heparin-coated ECC system (n = 11). Patients’ characteristics as well as surgical and anesthesiological procedure did not differ between the groups. Total counts did not differ significantly between the three groups. Intraoperative events in individual patients may lead to massive embolus generation overcoming positive properties of a distinct ECC system.
Long-Term Outcome after Local Intra-Arterial Fibrinolysis of Basilar Artery Thrombosis
Authors: Berg-Dammer E. , Felber S.R. , Henkes H. , Nahser H.C. , Kühne D.
Published: April 2003

Thrombolytic therapy of acute basilar artery (BA) thrombosis has been shown to reduce mortality and avoid a fatal outcome. Objective of this study was to investigate the long-term clinical outcome following intra-arterial fibrinolysis of occlusions of the BA. We retrospectively analyzed the clinical records and neuroradiologic results of 20 consecutive patients who had intra-arterial fibrinolysis of acute occlusions of the BA between 1982 and 1990. All patients were followed neurologically for a period of up to 12 years, including assessment of the Barthel index (BI) and brain CT or MRI studies. At the time of treatment, 6 patients were somnolent and 14 comatose, and tetraparesis was present in 15. The time between the onset of symptoms and treatment ranged from 1 to 48 h. The mortality rate was 35% (7/20 patients). Functional outcome was excellent in 9, 78%, of 13 survivors (BI <85). During the cumulative follow-up period (125 patient years) there was 1 death from myocardial infarction and 1 death from pneumonia. Vascular events during follow-up were myocardial infarction (n = 3) and a single cerebral transient ischemic attack. Despite the fact that our series was biased towards patients with severe symptoms, 65% (13/20) survived, and 78% of the survivors reached independence in daily life. These results provide evidence that local fibrinolysis of BA occlusion reduces mortality, and the long-term prognosis of the survivors is better than previously thought. None of our patients had a further stroke during the follow-up period, which indicates that acute BA occlusion is not a strong indicator for advanced arteriosclerotic disease.
The Usefulness of Ratios for Allocation Decisions: The Case of Stroke
Authors: Ament A. , Evers S. , Baltussen R.
Published: April 2003

Economic evaluation is becoming increasingly important in the field of stroke as well. The results of economic evaluation can be expressed in cost per quality-adjusted life years (QALY) gained, which enables policy makers to compare the relative efficiency of different interventions regarding different diseases. Although using the concept of QALY is preferable from a theoretical point of view, in medical practice more often cost-effectiveness analysis (CEA), and not cost-utility analysis, is applied for practical reasons. One of the main limitations of CEA is that the results may be compared only with results of other CEAs, using the same effect parameter. The calculation of cost-effectiveness ratios (CERs) in many cases is misleading for resource allocation. Effects should be expressed in interval or ratio scales in order to calculate CERs, which is rarely the case. The calculation of a CER in a CEA should only be performed if, and only if, the investigator is convinced that there is a constant relation between the specific effect parameter and the ultimate gain in health.
Detection of Right-to-Left Shunt with Ultrasound Contrast Agent and Transcranial Doppler Sonography
Authors: Jauss M. , Zanette E.
Published: April 2003

An international Consensus Meeting to determine a standard in the examination technique for the detection of right-to-left shunt (RLS) using contrast transcranial Doppler sonography (TCD) led to the following recommendations to standardize the examination procedure: The patient should be prepared with an 18-gauge needle inserted into the cubital vein and should be in the supine position. Insonation of at least one middle cerebral artery (MCA) using TCD is performed. The contrast agent is prepared using 9 ml isotonic saline solution and 1 ml air mixed with a three-way stopcock by exchange of saline/air mixture between the syringes and injected as a bolus. In case of little or no detection of microbubbles (MB) in the MCA under basal conditions, the examination will be repeated using the Valsalva maneuver (VM). Contrast agent will be injected 5 s before the start of the VM; the overall VM duration should be 10 s. The patient should start the VM on examiner’s command. The strength of the VM can be controlled by peak flow velocity of the Doppler curve. The time when the first MB appears at the MCA level will be noted. A four-level categorization according to the MB count should be applied: (1) 0 MB (negative result); (2) 1–10 MB; (3) >10 MB and no curtain, and (4) curtain. (‘Curtain’ refers to a shower of MB, where a single bubble cannot be identified.) The results should be documented for basal condition and VM testing separately. The clinical significance of the diagnosis of a RLS in a particular patient is not fully evaluated and requires further studies. A minimum amount of MB suggestive of a clinical relevant RLS is not yet established. It probably depends on interindividual differences in hemodynamics that are currently not fully understood. Transesophageal echocardiography remains the gold standard for detection of a patent foramen ovale or an atrial septum defect. However, TCD with a contrast agent has been turned out as a potential method to diagnose a RLS in several studies which have been published during the last years, and a RLS other than at the atrial level may be detected only by this method. Furthermore, the VM can be applied more comfortably and more reliably during Doppler examination than during transesophageal echocardiography.
Ecological Study of Streptococcus mutans, Streptococcus sobrinus and Lactobacillus spp. at Sub-Sites from Approximal Dental Plaque from Children
Authors: Babaahmady K.G. , Challacombe S.J. , Marsh P.D. , Newman H.N.
Published: April 2003

Previous immunofluorescence (IF) studies have indicated that Streptococcus mutans may preferentially colonise specific sub-sites within approximal plaque. The present study aimed to extend these observations to other mutans streptococci and lactobacilli in such gingival margin plaque. Two hundred and seventy approximal plaque samples were taken from 90 teeth (3 from each tooth) in 64 children; three gingival margin sub-sites in relation to the contact area: away from (A), to the side of (S) and below (B) the contact area. Samples were processed by indirect IF using high-titred polyclonal anti-S. mutans ‘c’, anti-S. sobrinus ‘d’, anti-L. casei and anti-L. acidophilus antisera. An overall positive association was found between S. mutans ‘c’ and S. sobrinus ‘d’ (p < 0.001). Significant differences (p < 0.1) were found between the proportional counts at each sub-site for S. mutans ‘c’: A = 39%, S = 51% and B = 70%, and for S. sobrinus ‘d’ 21, 33 and 49%. Mutans streptococci (MS) appeared to preferentially colonise the sub-site below the contact area (B = 81%), compared with sub-sites A and S (48 and 62%, respectively). S. mutans ‘c’ and S. sobrinus ‘d’ were detected together at sub-sites A = 12%, S = 22%, and B = 38%, with proportional counts at B sites being higher than those at A (B > A, p < 0.01, and B > S, p < 0.05). Lactobacillus spp. were isolated rarely, and were usually found together with MS. There was a positive relationship between the presence of lactobacilli or MS and caries (white spot lesions only), although these species could frequently be isolated from non-carious sites. The presence of both S. mutans ‘c’ and S. sobrinus ‘d’ were strongly correlated with early caries lesions. In addition, this study confirmed the variation in the microflora at different sub-sites within approximal dental plaque.
In situ Fluoride Retention in Enamel and Dentine after the Use of an Amine Fluoride Dentifrice and Amine Fluoride/Sodium Fluoride Mouthrinse
Authors: van Strijp A.J.P. , Buijs M.J. , ten Cate J.M.
Published: April 2003

The aim of this in situ investigation was to study the effect of an amine fluoride/sodium fluoride mouthrinse (total F = 250 ppm) in addition to an amine fluoride dentifrice (F = 1,250 ppm) on the amount of acquired fluoride in enamel and dentine. In the partial prosthesis of 12 participants a combined specimen of slightly demineralized enamel and dentine was placed. During two consecutive experiments, each lasting 3 weeks, the participants used an amine fluoride dentifrice alone or in combination with a fluoride mouthrinse. After the in situ period the specimens were retrieved and both the enamel and the dentine specimens were analysed for the amount of KOH–soluble fluoride and structurally bound fluoride. The results showed a significant increase in both KOH–soluble and structurally bound fluoride in enamel and dentine when a fluoride mouthrinse was used. Whether the rinsing procedure was performed immediately after toothbrushing or with a delay of 2 h did not influence the results. Furthermore it was shown that dentine acquired substantially more fluoride than enamel during the experimental period. The results indicate that a fluoride mouthrinse used in addition to a fluoride dentifrice may have a beneficial effect on the protection of enamel and dentine against caries.
Clinical Evaluation of Efficacy and Safety of a New Method for Chemo–Mechanical Removal of Caries
Authors: Ericson D. , Zimmerman M. , Raber H. , Götrick B. , Bornstein R. , Thorell J.
Published: April 2003

The aim of the study was to evaluate the clinical efficacy and safety of a new method (Carisolv™) for chemo–mechanical removal of caries. At four centres, 137 consecutive patients (64 females and 73 males aged 3–85 years, mean 35) entered a prospective, controlled, randomised open study. One primary caries lesion with distinct dentine involvement was selected per patient. A total of 116 lesions in permanent and 21 in deciduous teeth were selected. Caries was removed with traditional drilling or the new method. Gel was applied onto the carious dentine and the softened caries gently removed with specially designed hand instruments. New gel was applied and the procedure was repeated until no more debris could be removed and the surface was hard as judged by clinical criteria (probing and visual inspection). An independent examiner judged the cavity being caries–free or not, using clinical criteria. One hundred and thirteen patients were randomised for gel treatment and 24 for drilling. Three patients selected for drilling did not complete the treatment. Total caries removal was achieved in 106 cases with gel and in 19 with drilling. The reasons for incomplete caries removal were step–by–step excavation in 5 cases, unsuccessful caries removal in 1 case for each treatment, while 2 cases refused inspection. Mean (± SD) time for caries removal was 10.4 (±6.1) min with the gel method and 4.4 (±2.2) min with drilling. Mean volume of gel used was 0.4 (±0.2) ml. Eighty–two of 107 patients perceived that the new method caused less discomfort compared to drilling. Dentine caries was effectively removed using the Carisolv method without any adverse reactions.
The Effect of Window Width on the Demineralization of Human Dentine and Enamel
Authors: Ruben J. , Arends J. , Christoffersen J.
Published: April 2003

When lesion formation in dental enamel or dentine is studied in vitro, a well–defined area of the material, a 'window', is exposed to the demineralization medium. In the present experiments, we report the effect of window width on lesion formation in enamel and dentine. Rectangular windows, longest dimension always 5 mm and shortest dimension varying from 0.5 to 5 mm, were exposed to demineralization media. Lesions in dentine were formed by placing the specimens in an acidified unstirred 6% carboxymethyl cellulose (CMC) gel, an unstirred 0.5% CMC gel, a mildly stirred 0.5% CMC gel, or in a mildly stirred demineralization solution. Lesions in enamel were formed only in an unstirred acidified 6% CMC gel. pH in the demineralization media was 5.0 in all experiments. The microradiographic technique was used to assess lesion depth and mineral loss (vol%·μm) of lesions formed. Lesions formed in the unstirred gels were deeper, and there was a larger mineral loss, the narrower the window. There was no effect of window size on lesions formed in stirred systems. These effects can be explained by the strong dependence of concentration gradient in stirred gels just outside the exposed window on the window size. The phenomenon found here in vitro may at least partly explain why secondary caries may lead to localized, but relatively deep, lesions.
The Remineralization of EDTA–Treated Human Dentine
Authors: Kawasaki K. , Ruben J. , Stokroos I. , Takagi O. , Arends J.
Published: April 2003

The remineralization of whole human dentine treated with a neutral EDTA solution was investigated: the treatment periods were 15, 30 and 120 min. From the literature it is known that EDTA removes noncollagenous proteins (NCPs) from dentine powders. In order to extract more phosphoproteins from dentine lesions, in part of this work samples were also treated with 1 M NaCl or 4 M guanidine chloride solutions. All the dentine samples after the treatments mentioned were immersed subsequently in a remineralizing solution without fluoride for 2 weeks and microradiographed. To investigate the effects of fluoride, samples treated with EDTA for 120 min were also remineralized with 2ppm fluoride in solution. The results presented show that: (1) Measurable remineralization did not occur when fluoride was free in the remineralizing solution. Because remineralization occurred neither at the lesion front nor in the nonmineral part of the surface–softened tissue, presumably the NCPs (inhibitors) of underlying dentine diffused into the tissue during the remineralization period. (2) 2ppm fluoride caused remineralization at the lesion front. In this case we assume fluoride either acted as nucleating agent or overcame the NCP effects at the lesion front.
Plaque pH and Associated Parameters in Relation to Caries
Authors: Dong Y.-M. , Pearce E.I.F. , Yue L. , Larsen M.J. , Gao X.-J. , Wang J.-D.
Published: April 2003

Intensified plaque acidogenicity in caries–prone subjects was reported many years ago, but emerging evidence has suggested that the relationship may not be as strong as once thought. We have now determined a range of acidogenicity variables in subjects having both caries prevalence and incidence data, and have included plaque mineral data in the analysis. pH measurements were made in 20 randomly selected subjects from a high–caries group (mean DMFS = 8.95) and 20 from a caries–free group of Beijing children aged 12 years participating in a caries prediction study. Subgroups with a 12–month DMFS increment ≥2 or = 0 were also formed from the two groups, respectively. Measurements were made with an iridium oxide electrode inserted between teeth 13/14, 23/24, 34/35 and 44/45, before and every 5 min for 30 min after rinsing with 10% sucrose, and the 4 resulting ‘Stephan curves’ averaged using a plaque pH analysis program. Supragingival plaque was collected from buccal and lingual smooth surfaces of posterior and upper anterior teeth and its acid extract analysed for Ca, P and F. Caries–free subjects (based on past experience) had a significantly higher maximum plaque pH and pH value after 30 min (reflecting a faster return to resting pH), a lower minimum enamel dissolution capacity of plaque and recorded less time below pH 7.0 than did high–caries subjects. No other differences were significant, including those of the principal acidogenic parameters ‘minimum pH attained after a sugar rinse’, ‘curve area below the critical pH of 5.5’ and ‘time below the critical pH’. Selection of the caries groups on the basis of both experience and incidence did not reveal significant differences in more parameters. Upper arch plaque was significantly more acidogenic than lower arch plaque, and there was a consistently strong association between upper and lower arch values in individuals. Ca, P and F in the subjects’ plaque had little or no influence on the principal acidogenic parameters. Our failure to find a relationship between caries prevalence or activity and these principal acidogenicity parameters may be related to differences between fissure and smooth surface plaque, temporal variations in acidogenicity and/or to use of F toothpaste during the 1–year observation period. These results support the view that factors such as the frequency of acidogenic episodes may be more important in caries progression than the degree of acidogenicity during any one episode.
Use of Variable Remineralization Periods to Improve the Abrasion Resistance of Previously Eroded Enamel
Authors: Attin T. , Buchalla W. , Gollner M. , Hellwig E.
Published: April 2003

The objective of the study was to evaluate the period of remineralization needed to re–establish the resistance of eroded enamel against brushing abrasion. Enamel specimens were prepared from 84 polished bovine incisors. The samples were evenly distributed among 7 groups (A–G) and submitted to ten alternating de– and remineralization cycles which included abrasion by toothbrushing. Demineralization was accomplished by immersing the specimens in the erosive soft drink Sprite Light® for 1 min. Remineralization was performed by storing the samples in artificial saliva for either 0 min (A), 10 min (B), 60 min (C) or 240 min (D). After each remineralization, the specimens were brushed in an automatic brushing machine. Group E (erosion and 240 min remineralization, but no brushing) group F (erosion, but no remineralization and no brushing), and group G (brushing, but no erosion and no remineralization) served as controls. After performing the cycles, loss of enamel was determined by profilometry. The following values (mean ± SD) were obtained and statistically analyzed (p<0.05): group A (5.16±1.26 μm), B (2.47±0.68 μm), C (1.72±0.75 μm), D (1.11±0.42 μm), E (0.81±0.23 μm), F (1.04±0.31 μm), G (0.22±0.15 μm). Only the differences between groups D, E, and F were statistically not significant. Under the chosen in vitro conditions, it is concluded that abrasion resistance of eroded enamel continuously increases with remineralization time. However, even after a period of 1 h of remineralization, abrasion of previously eroded enamel is increased
Relationship between Mineral Distributions in Dentine Lesions and Subsequent Remineralization in vitro
Authors: Kawasaki K. , Ruben J. , Tsuda H. , Huysmans M.C.D.N.J.M. , Takagi O.
Published: April 2003

Though the mineral distribution of the dentine carious lesion varies largely from tooth to tooth and from patient to patient, there are two main distribution profiles that characterize natural carious lesions in dentine. These profiles include softened and subsurface lesion types. The mineral distribution relationship between the starting profile and the profile after remineralization is not known. In order to study the relational aspects, we have produced demineralized dentine samples in vitro with mineral profiles similar to those of typical natural carious lesions, and subsequently remineralized the samples in a remineralizing solution with various fluoride concentrations (0, 2 and 10 ppm F). The mineral distributions were obtained by using an improved microradiographic technique. In addition, the nature of deposited mineral was analyzed by diamond–coupled total internal reflectance spectroscopy. Definite relationship was observed between the original lesion mineral distribution and the mineral distributions following remineralization. The amount of mineral present in approximately the first 50 μm of the lesion influenced the overall mineral profile after remineralization, possibly through influencing ion transport. If the amount was high (> approximately 10 vol%), the deposited mineral was confined to the surface (0–50 μm). The original mineral at those depths acted like a nucleus of mineral regrowth when the amount of residual mineral was intermediate, and like a transport barrier when the surface layer was well mineralized. If a surface barrier was not present, mineral was deposited at deeper depths in the lesion. Fluoride effect on dentine remineralization was dependent on the original mineral content and its distribution in the lesion. Although a high concentration of fluoride was very effective in low–mineral lesions, it produced hyperremineralization on well–mineralized subsurface lesions so that it prevented effective remineralization especially in deeper lesions.
Antimicrobial Effect of a Novel Ozone– Generating Device on Micro–Organisms Associated with Primary Root Carious Lesions in vitro
Authors: Baysan A. , Whiley R.A. , Lynch E.
Published: April 2003

The aims of this present study were (1) to assess the antimicrobial effect of ozone from a novel ozone–generating device (Heolozone, USA) [0.052% (v/v) in air delivered at a rate of 13.33 ml·s–1] on primary root carious lesions (PRCLs) and (2) to evaluate the efficacy of ozone specifically on Streptococcus mutans and Streptococcus sobrinus. In study 1, 40 soft PRCLs from freshly extracted teeth were randomly divided into two groups to test the antimicrobial effect on PRCLs from exposure to ozonated water for either 10 or 20 s. Half of a lesion was removed using a sterile excavator. Subsequently, the remaining lesion was exposed to the ozonised water for a period of either 10 or 20 s (corresponding to 0.069 or 0.138 ml of ozone, respectively). Using paired Student t tests, a significant (p<0.001) reduction (mean ± SE) was observed in the ozone–treated groups with either a 10–second (log10 3.57±0.37) or 20–second (log10 3.77±0.42) ozone application compared with the control groups (log10 5.91±0.15 and log10 6.18±0.21, respectively). In study 2, 40 sterile saliva–coated glass beads were randomly divided into two groups for each micro–organism. One glass bead was put into each bijou bottle with 3 ml of Todd–Hewitt broth. S. mutans and S. sobrinus were inoculated anaerobically overnight. Each glass bead was then washed with 2 ml of phosphate–buffered saline. Immediately, 10 s of ozone gas was applied to each glass bead in the test groups. There was a significant (p<0.0001) reduction (mean ± SE) in ozone–treated samples for S. mutans (log10 1.01±0.27) and S. sobrinus (log10 1.09±0.36) compared with the control samples (log10 3.93±0.07 and log10 4.61±0.13, respectively). This treatment regime is an effective, quick, conservative and simple method to kill micro–organisms in PRCLs. Ozone gas application for a period of 10 s was also capable of reducing the numbers of S. mutans and S. sobrinus on saliva–coated glass beads in vitro.
Recent Developments in the Molecular Characterization of Barrett’s Esophagus
Authors: Fitzgerald Rebecca C. , Triadafilopoulos George
Published: April 2003

Barrett’s esophagus, or specialized intestinal metaplasia, is a common condition associated with gastroesophageal reflux and an increased risk for adenocarcinoma of the esophagus and gastric cardia. Currently, clinical surveillance for early detection of adenocarcinoma relies on the histopathological assessment of dysplasia. In this review we present data from the published literature, and combine this with results from our own research, to address what is currently known about the environmental factors and the molecular changes thought to be important in the pathogenesis of Barrett’s esophagus. The most important and well-characterized molecular changes, preceding the development of dysplasia, are alterations in the p53 and erbB-2 genes and aneuploidy. These molecular changes, as well as environmental influences, such as the quality and quantity of gastroduodenal refluxate, may result in abnormal cell proliferation which in turn promotes further genetic abnormalities and deregulation of cell growth. The identification of molecular changes, in the context of predisposing environmental factors, will enhance our understanding of the malignant progression of Barrett’s esophagus leading to more effective surveillance and treatment.
Genetic Epidemiology in Inflammatory Bowel Disease
Authors: Binder Vibeke
Published: April 2003

Family studies of different designs have been carried out in the last few years. Five to ten percent of patients have another case of inflammatory bowel disease (IBD) among their first-degree relatives, with about 75–80% concordance for the same disease within the family. About 20% of multi-affected families present both cases with ulcerative colitis and Crohn’s disease. The population relative risk in first-degree relatives of patients show a 14–15 times higher prevalence of IBD. Prevalence values of 1.5–3.5% in first-degree relatives have been found, with an even higher calculated lifetime risk especially in offspring and siblings of patients with IBD. Earlier disease onset in offspring of patients with IBD have consistently been found, and genetic anticipation has been hypothesized. The phenomenon, however, may be a result of a combination of a time trend – increasing the incidence of Crohn’s disease – and the fact that patients with early onset of IBD may have lower fertility and therefore may be underrepresented in the parent-child pairs studied. Twin studies have shown significantly higher concordance rates in monozygotic than in dizygotic twins. Further, the concordance rate in monozygotic twins is higher in Crohn’s disease than in ulcerative colitis, indicating a stronger genetic influence in this condition. Disease course and prognosis within families have been studied without convincing concordance found in this respect among family members.
Renal Function in Compensated Hepatic Cirrhosis: Effects of an Amino Acid Infusion and Relationship with Nitric Acid
Authors: Rodriquez A. , Martin A. , Oterino J.A. , Blanco I. , Jimenez M. , Perez A. , Novoa J.M.
Published: April 2003

Aims: In order to assess the possible participation of nitric oxide (NO) in renal function during compensated hepatic cirrhosis, we studied renal function, the plasma and urinary levels of cGMP and the concentration of nitrates and nitrites, as markers of NO synthesis in blood and urine, in 10 patients with Child A hepatic cirrhosis as compared with 10 control subjects, both under basal conditions and during stimulation (amino acid-induced glomerular hyperfiltration). Methods: To study renal function, the glomerular filtration rate (GFR), effective renal plasma flow (ERPF), renal functional reserve (RFR), renal venous resistance (RVR) and the filtration fraction (FF) were measured. Renin and aldosterone levels were determined to assess the possible involvement of these compounds in the renin-angiotensin-aldosterone axis. Results: GFR and ERPF were significantly lower in the patients with cirrhosis than in the controls (mean GFR: 82±12.3 vs. 105±15 ml/min, p = 0.01; ERPF 452±86 vs. 543±56 ml/min, p = 0.002). The RFR value was similar in both groups. In the basal situation cGMP levels were higher in plasma and urine in patients with cirrhosis than in the controls (plasma cGMP in cirrhosis 8.4±2.4 vs. 4.2±3.5 pmol/ml; urine cGMP in cirrhosis 1.2±2.1 vs. 0.68±0.1 pmol/ml). The NO levels were also higher in plasma and urine in patients with cirrhosis vs. controls (plasma NO in cirrhosis 45.5±9.2 vs. 30.3±1.2 μmol/l; urinary NO in cirrhosis 6.2±1.3 vs. 3.1±2.3 μmol/ml). In both groups the amino acid perfusion increased GFR, ERPF, cGMP and NO levels in plasma and urine. In the patients with cirrhosis the RVR decreased significantly during perfusion and no noteworthy changes in FF were observed. The GFR values observed during amino acid perfusion were similar in patients with cirrhosis and portal hypertension to those observed in the controls (27.2±12 vs. 25.3±16%). However, the changes induced the ERPF were more marked in patients with cirrhosis (cirrhosis 35.3±15 vs. 22.2±13%, p = 0.02). Conclusions: The present findings point to certain alterations in renal function in patients with hepatic cirrhosis and portal hypertension without ascitis, a clear difference being visible between the ERPF and GFR following amino acid-induced stimulation. The significant elevation in cGMP and NO levels in plasma and urine implies a maintained vasodilatory action that may at least partly compensate the vasoconstrictor effects of angiotensin II.
Pathophysiology and Pharmacological Treatment of Gastroesophageal Reflux Disease
Authors: Storr M. , Meining A. , Allescher H.-D.
Published: April 2003

Gastroesophageal reflux disease (GERD) is one of the most common diagnoses in a gastroenterologist’s practice. Gastroesophageal reflux describes the retrograde movement of gastric contents through the lower esophageal sphincter (LES) to the esophagus. It is a common, normal phenomenon which may occur with or without accompanying symptoms. Symptoms associated with GERD include heartburn, acid regurgitation, noncardiac chest pain, dysphagia, globus pharyngitis, chronic cough, asthma, hoarseness, laryngitis, chronic sinusitis and dental erosions. The introduction of fiberoptic instruments and ambulatory devices for continuous monitoring of esophageal pH (24-hour pH monitoring) has led to great improvement in the ability to diagnose reflux disease and reflux-associated complications. The development of pathological reflux and GERD can be attributed to many factors. Pathophysiology of GERD includes incompetent LES because of a decreased LES pressure, transient lower esophageal sphincter relaxations (TLESRs) and deficient or delayed esophageal acid clearance. Uncomplicated GER may be treated by modification of life style and eating habits in an early stage of GERD. The various agents currently used for treatment of GERD include mucoprotective substances, antacids, H2 blockers, prokinetics and proton pump inhibitors. Although these drugs are effective, they do not necessarily influence the underlying causes of the disease by improving the esophageal clearance, increasing the LESP or reducing the frequency of TLESRs. The following article gives an overview regarding current concepts of the pathophysiology and pharmacological treatment of GERD.
Epidemiological Dementia Index: A Screening Instrument for Alzheimer’s Disease and Other Types of Dementia Suitable for Use in Populations with Low Education Level
Authors: Fountoulakis K.N. , Tsolaki M. , Mohs R.C. , Kazis A.
Published: April 2003

Introduction: MMSE and CAMCOG are neuropsychological scales developed for use in everyday clinical practice and epidemiological surveys. Material and Methods: These two instruments were used as part of the assessment during an epidemiological survey in the municipality of Pylaia, Greece. The project was based on the World Health Organization Program for Research on Aging and Age-Associated Dementias (1992). It had two phases. During phase I, nursing students collected demographic data, risk factors, personal and family history data and they applied MMSE, CAMCOG and scales of everyday life functioning. During phase II, 4 physicians examined all subjects that manifested possible cognitive deterioration (MMSE<27), in order to reach a final diagnosis. The final diagnosis was made according to DSM-IV and NINCDS-ADRDA criteria. MMSE and CAMCOG were not taken into consideration in the diagnostic process. Three hundred and eighty subjects were initially screened. All were aged over 70 years. After the exclusion of subjects who were illiterate, blind, etc., the results of 277 subjects were finally analyzed. Subjects with 6 years of education or less accounted for 92.42% of the total study sample. Twelve of them (5.33%) suffered from Alzheimer’s disease, 7 from vascular dementia (2.52%) and 1 suffered from secondary dementia (0.36%). Results: MMSE exceeded 90% sensitivity at the level 22/23 and specificity at 14/15. The levels for CAMCOG were 56/57 and 43/44, respectively. This low performance of both tests is to a large extent due to the functional illiteracy of elderly individuals in Greece, to possible coexistence of mood disorders or simply to lack of cooperation. The analysis of data led to the development of an Epidemiological Dementia Index (EDI), with a scale ranging from 0 to 7. Nondemented subjects had a mean EDI of 5.12 (SD = 1.67) and demented patients had a mean EDI of 1.6 (SD = 1.92). At the level 4/5 sensitivity was 93.33. Specificity was 93.56 at the level 2/3.
Predisposing and Precipitating Factors for Delirium in Hospitalized Older Patients
Authors: Inouye Sharon K.
Published: April 2003

Delirium is a common and serious problem for older hospitalized patients. This investigation proposes a multifactorial model of delirium etiology, involving a complex interrelationship of predisposing (vulnerability) factors and precipitating factors (acute insults). An overview of risk factors for delirium identified in 14 studies published since 1980 is provided. Although these studies identify key risk factors for delirium, they do not allow the examination of the interrelationship of predisposing and precipitating factors. Thus, we present two prospective cohort studies by our group which empirically examine: (1) predisposing (vulnerability) factors, (2) precipitating factors, and (3) the interrelationship of predisposing and precipitating factors. Understanding these risk factors is the key to developing appropriate preventive strategies and to target intermediate and high risk patients for intervention efforts.
Drugs That Induce Delirium
Authors: Karlsson Ingvar
Published: April 2003

Drug-induced delirium is often seen in clinical practice. Most knowledge about delirium-inducing drugs comes from reports on side effects, and few systematic studies have been done in the field. Delirium is strongly associated with anticholinergic activity; drugs of different classes, including tricyclic antidepressants and traditional high-dose neuroleptics, constitute a high-risk group. A large number of drugs, including benzodiazepines, sedatives, dopamine-activating drugs, antiepileptics, histamine H2 receptor blockers, digitalis and analgesics, are less frequently associated with delirious reactions and constitute a medium-high-risk group. Some of these drugs do not have anticholinergic effects but in vitro have shown to bind to muscarine receptors. The risk of inducing delirium in frail elderly and demented persons clearly suggests that drugs which might induced delirium should be avoided.
Neuropathological Substrates of Dementia and Depression in Vascular Dementia, with a Particular Focus on Cases with Small Infarct Volumes
Authors: Ballard Clive , McKeith Ian , O’Brien John , Kalaria Rajesh , Jaros Evelyn , Ince Paul , Perry Robert
Published: April 2003

The neuropathological substrates of dementia and depression were evaluated in 30 patients with cerebrovascular disease and significant cognitive impairment (VaD), with a particular focus on patients with small infarct volumes (<15 ml). VaD patients with small infarct volumes had a similar degree of cognitive impairment to those with larger infarct volumes (>15 ml) but were significantly more likely to be depressed and to have areas of microinfarction. A review of individual cases with small infarct volumes suggested that the combination of microinfarction, diffuse white matter disease and perivascular changes, or the overlap of neurodegenerative pathologies and microvascular changes were particularly important. Microinfarction was also significantly associated with major depression.
Postnatal Development of the Rat Neostriatum: Electrophysiological, Light- and Electron-Microscopic Studies
Authors: Tepper James M. , Sharpe Neal A. , Koós Tibor Z. , Trent Francine
Published: April 2003

The postnatal development of the electrophysiological properties and morphology of rat neostriatum was studied using in vivo and in vitro intracellular recording and biocytin staining and light and electron microscopy. The principal neurons, the medium spiny neurons, were found to undergo a protracted postnatal development of their electrophysiological and morphological characteristics. Most of the intrinsic membrane properties of medium spiny neurons came to resemble those in the adult by the end of the 3rd postnatal week. Synaptic responses and spontaneous activity patterns in medium spiny neurons were dependent on the arrival and functional maturation of excitatory afferents from cortex and thalamus and did not become adult-like until the end of the 1st postnatal month.
Can Experimental Conditions Explain the Discrepancy over Glutamate Stimulation of Aerobic Glycolysis?
Authors: Hertz Leif , Swanson Raymond A. , Newman George C. , Marrif Husnia , Juurlink B.H.J. , Peng Liang
Published: April 2003

Uncertainty reigns over whether or not glutamate uptake in astrocytes leads to strong stimulation of glucose utilization, measured as accumulation of radioactive deoxyglucose-6-phosphate. This is an important issue, not only because glutamate is the major excitatory transmitter, but also because it has been postulated that glutamate-induced stimulation of glycolysis links brain excitation with activation of energy production. The effect of glutamate on deoxyglucose utilization in cultured rat and mouse astrocytes grown in different media and incubated under various conditions during the deoxyglucose assay has, therefore, been studied. Under most conditions, no stimulation occurred but rather a decrease in deoxyglucose utilization during exposure to glutamate; under certain conditions, the contribution of non-metabolized deoxyglucose to the intracellular 14C signal was significant.
Infantile Spasms: The Development of Nonverbal Communication after Epilepsy Surgery
Authors: Caplan Rochelle , Guthrie Donald , Komo Scott , Shields W. Donald , Sigmann Marian
Published: April 2003

The postoperative development of nonverbal communication was studied in 29 children, aged 18.2 (SD = 11.54) months, who underwent multilobar resection or hemispherectomy for intractable symptomatic infantile spasms (IS). Using the Early Social Communication Scale, the IS subjects had little, if any, social interaction, joint attention or behavior regulation before surgery. After a mean follow-up of 24 months, most of the children continued to have delayed nonverbal communication skills compared to normal children. Seizure-related, surgical and cognitive factors were unrelated to the postsurgical development of nonverbal communication. The children with right-sided surgery had a statistically significant increase in the use of social interaction but not in other gestural behaviors. Removal of the frontal lobe was not related to the nonverbal communication outcome. The study’s findings suggest that impaired use of nonverbal communication might be a feature of surgically treated children with medically intractable IS.
Regulation of Neuronal Differentiation in Human CNS Stem Cell Progeny by Leukemia Inhibitory Factor
Authors: Galli Rossella , Pagano Stefano F. , Gritti Angela , Vescovi Angelo L.
Published: April 2003

The generation of diverse types of neural cells during development occurs through the progressive restriction of the fate potential of neuroepithelial progenitor cells. This process is controlled by factors intrinsic and extrinsic to the cell. While the effect of extrinsic cues on multipotent stem cells of the murine central nervous system (CNS) is becoming clearer, little is known of neural stem cells of human origin. We sought to establish the roles played by two cytokines, leukemia inhibitory (LIF) and ciliary neurotrophic factor (CNTF), and by nerve growth factor (NGF) and platelet-derived growth factor (PDGF) in regulating neuronal and astroglial differentiation in cultured embryonic diencephalic human stem cells. While NGF did not influence either neuronal or glial formation, PDGF surprisingly decreased the percentage of stem cell-generated neurons, an effect opposite to that observed in murine progenitors. Furthermore, while we confirmed the known ability of LIF and CNTF to support astroglial differentiation, we also observed that, in contrast with their murine counterparts, the fraction of CNS stem cell-generated neurons in human cultures was enhanced twofold in the presence of both cytokines. These findings highlight important differences between humans and rodents in regard to the way epigenetic cues regulate the function of neural stem cells.
Dendritic Alterations of Cerebellar Purkinje Neurons in Postnatally Lead-Exposed Kittens
Authors: Patrick George W. , Anderson William J.
Published: April 2003

Many investigations have sought to determine the effect of lead exposure on the development of the cerebellum. This study addresses the effects of postnatal lead exposure in kittens on dendritic development of Purkinje cells. Golgi-Cox filled cells were used to measure dendritic branching patterns, spine density, height, width and distance from the cerebellar surface. The results revealed a significant increase in spine density and altered patterns of dendritic branching. Complex dendritic branching was evident with a progressive shift in peak branching peripherally. Lead-exposed Purkinje cells showed early sprouting with subsequent pruning. At 5 weeks of age dendritic branches on experimental cells were increased along the entire dendritic extent. Control Purkinje cells showed initial sprouting with subsequent pruning. Normal developmental growth spurts and lead-induced effects were evident on dendritic height, width and distance from the surface. Cerebella stained with hematoxylin and eosin and cresyl violet acetate showed no evidence of vascular damage or other pathologies. These findings corroborate the evidence of hyperspiny dendritic formation representing an important mechanism of neuronal plasticity. In regard to morphological effects of lead on rodents, the hyperspiny Purkinje cell dendrites and patterns of dendritic growth in lead-treated kittens offer an alternative interpretation of neurobehavioral findings of lead-burdened children. The results are discussed with reference to other aspects of lead exposure and neural development.
Keratoacanthoma Developing on a Pigmented Patch in Incontinentia pigmenti
Authors: Sakai Hiroyuki , Minami Masako , Satoh Emi , Matsuo Shinobu , Iizuka Hajime
Published: April 2003

Cutaneous manifestations of incontinentia pigmenti (IP) have classically been described as three sequential stages: an initial vesicobullous stage, a verrucous stage and a stage of swirled pigmentation. Verrucous lesions tend to last longer than vesicobullous eruptions, often persisting until 1 year of age. However, adult patients with verrucous lesions are rare. We report a case of keratoacanthoma with marked dyskeratosis on a pigmented patch in a 20-year-old woman. This tumor, like subungual keratotic tumors of IP, might have been developed as one of the late manifestations of the disease.
Extreme UV Exposure of Professional Cyclists
Authors: Moehrle Matthias , Heinrich Lothar , Schmid Andreas , Garbe Claus
Published: April 2003

Background: The most important risk factor for the development of melanoma and non-melanoma skin cancer is thought to be ultraviolet (UV) radiation. To date there is no quantification of the UV exposure of outdoor sports professionals training and competing at high solar UV levels. Methods: During eight stages of the ‘Tour de Suisse’ cycling race, the UV exposure of 6 professional cyclists was monitored with Bacillus subtilis spore film dosimeters. Results: The measurements showed a personal UV exposure between 0.2 minimal erythema dose (MED) during the prologue and 17.2 MED during a mountain stage. The mean daily personal exposure of all full stages (prologue excluded) was 8.1 MED. The personal exposure level determined during these races exceeded international exposure limits by more than 30 times. Conclusion: Therefore UV exposure of sports professionals should be limited by application of sun screens, protective clothing and training/competition at low insolation.