bluuebunny/crossref_metadata_2025 huggingface dataset:
BIFURCATION IN ASYMMETRICALLY COUPLED BVP OSCILLATORS
Authors: UETA TETSUSHI , KAWAKAMI HIROSHI
Published: June 2003

BVP oscillator is the simplest mathematical model describing dynamical behavior of neural activity. Large scale neural network can often be described naturally by coupled systems of BVP oscillators. However, even if two BVP oscillators are merely coupled by a linear element, the whole system exhibits complicated behavior. In this letter, we analyze coupled BVP oscillators with asymmetrical coupling structure, besides, each oscillator has different internal resistance. The system shows a rich variety of bifurcation phenomena and strange attractors. We calculate bifurcation diagrams in two-parameter plane around which the chaotic attractors mainly appear and confirm relaxant phenomena in the laboratory experiments. We also briefly report a conspicuous strange attractor.
FRACTALITY OF MONTHLY EXTREME MINIMUM TEMPERATURE
Authors: VALDEZ-CEPEDA RICARDO DAVID , HERNÁNDEZ-RAMÍREZ DANIEL , MENDOZA BLANCA , VALDÉS-GALICIA JOSÉ , MARAVILLA DOLORES
Published: June 2003

Interest in climate change has increased over the last 30 years due largely to global predictions associated with the greenhouse effect, which appear to lead to a substantial increase in planetary temperature. Implications of such results have led many scientists to examine climatic records from different regions of the world in order to understand temperature behavior. However, many researchers have noted that changes in temperature variability are also important in determining the future temperature distributions. In this context, we have analyzed a long-term record of monthly extreme minimum temperature registered at Guanajuato, Mexico. Data set was treated as a fractal profile to estimate the fractal dimension through variography (Dv) and power-spectral (Ds) approaches under two situations: (1) complete series, from January 1895 to December 1997 with 312 missing observations, and (2) partial series, from January, 1921 to April, 1963 with no missing values. In both cases, we obtained similar values for the two types of fractal dimensions meaning there is not a significant effect of missing values. The estimated fractal dimensions for the partial series (508 observations) are near 1.5 (Dv = 1.445 ± 0.06, Ds = 1.486 ± 0.155), which means monthly extreme minimum temperature is almost equally characterized by both short- and long-range variations. Evaluating through scaling arguments did not evidence multifractality in the scale range of two to 254 months. Then interpolation can make use of the fact that monthly extreme minimum temperature has a power-law spectrum. Interpolated data generated by this way may develop greater confidence in their capability to forecast near future climate.
Assessment of Decline in Health-Related Quality of Life among Angina-Free Patients Undergoing Coronary Artery Bypass Graft Surgery
Authors: Pirraglia Paul A. , Peterson Janey C. , Williams-Russo Pamela , Charlson Mary E.
Published: June 2003

Purpose: Coronary artery bypass graft (CABG) surgery generally decreases symptoms and improves quality of life, but for those patients without angina, prolongation of life takes precedence. We used the SF-36 to assess changes in health-related quality of life (HRQOL) among patients who were angina free prior to CABG compared to those reporting angina. Methods: We combined data from two randomized trials of hemodynamic management during surgery. Prior to CABG, demographic, clinical and SF-36 data were obtained. Patients were reevaluated at a 6-month follow-up. Patients with a decline of ≧15 points from baseline to follow-up for individual SF-36 domains and >5 points for summary components were classified as having a decline. We used logistic regression models that controlled for baseline SF-36 score and other baseline characteristics to assess HRQOL decline with respect to angina status. Results: Of 590 patients, 28% were angina free at baseline. A third of the patients angina free at baseline had a postoperative decline in physical function. Patients who were angina free at baseline were three times more likely to suffer a decline in physical function than those with angina (odds ratio 3.29, 95% confidence interval 1.86–5.82). This finding remained after addition of adverse outcomes to the model. Baseline angina status was not related to any other SF-36 domain or to physical or mental summary component scores. Major adverse outcomes did not differ between angina-free patients and those with angina. Conclusions: The incidence of patients reporting a decline in physical function after CABG was greater in patients without angina preoperatively, even when adjusting for baseline score. Given the substantial risk of decreased physical functioning, employing interventions to maintain HRQOL in this population should be considered.
Rosuvastatin – A Highly Effective New 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Inhibitor: Review of Clinical Trial Data at 10–40 mg Doses in Dyslipidemic Patients
Authors: Schuster Herbert
Published: June 2003

Rosuvastatin (Crestor®; licensed to AstraZeneca, Macclesfield, UK from Shionogi, Osaka, Japan) is a new statin with pharmacologic characteristics that translate into selectivity of effect in hepatic cells and enhanced potency in 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibition. It is approved for use at doses of 10–40 mg once daily to reduce low-density lipoprotein (LDL) cholesterol, increase high-density lipoprotein (HDL) cholesterol and improve other lipid measures in dyslipidemic patients. In a dose-ranging study in mild/moderate hypercholesterolemia, rosuvastatin reduced LDL cholesterol by 52–63% at 10–40 mg. Rosuvastatin 10 mg reduces LDL cholesterol significantly more than atorvastatin 10 mg, simvastatin 10–40 mg and pravastatin 10–40 mg, and enables significantly more patients to achieve National Cholesterol Education Program and Joint European Societies LDL cholesterol goals compared with each of these statins. Rosuvastatin also produces marked elevations in HDL cholesterol and maintains this effect across the dose range. Rosuvastatin favorably modifies triglycerides, LDL cholesterol and other lipid measures in patients with hypertriglyceridemia or mixed dyslipidemia, including diabetic patients, and may constitute a monotherapy option for many such patients. Rosuvastatin is well tolerated when used alone or in combination, exhibiting a safety profile similar to that of other available statins. Rosuvastatin offers considerable advantages for use in routine clinical practice.
Comparison of Transthoracic and Intraoperative Transesophageal Color Flow Doppler Assessment of Mitral and Aortic Regurgitation
Authors: Neuman Yoram M. , Brasch Andrea V. , Kobal Sergio , Khan Steven S. , Mirocha James M. , Naqvi Tasneem Z. , Siegel Robert J.
Published: June 2003

Background: We examined the agreement between transthoracic echocardiography (TTE) and intraoperative prepump transesophageal echocardiography (TEE) in the assessment of left-sided regurgitant lesions and echocardiographic variables associated with grading discrepancies. Methods: The TTE and prepump TEE studies of 54 patients undergoing aortic-valve replacement for aortic stenosis were reviewed. Agreement and correlation in assessment of aortic (AR) and mitral regurgitation (MR) severity were evaluated. Results: There was no significant difference between mean TTE and prepump TEE grading of MR (0.23 ± 0.19 vs. 0.21 ± 0.15 jet area/area of the left atrium, p = 0.49), but the correlation between the two methods was weak (r = 0.40, p = 0.003), with an exact agreement of 54%. Prepump TEE tended to grade AR as more severe (mean grade 1.43 ± 0.94 vs. 1.24 ± 0.75, p = 0.058). The correlation between the two methods in AR assessment was fair (r = 0.70, p = 0.0001) with an agreement of 59%. For MR and AR grading, no significant correlations between valvular regurgitation severity and blood pressure differences between preoperative TTE and prepump TEE were found. In 17% of cases, discrepancies in identifying severe mitral or aortic valve regurgitation could have affected patient management. Conclusions: There is modest agreement in MR and AR assessment between TTE and prepump TEE. Cardiologists, cardiac surgeons, and anesthesiologists must be aware of differences between these methods when using prepump TEE to guide intraoperative decisions.
MR Imaging of Arrhythmogenic Right Ventricular Cardiomyopathy: Morphologic Findings and Interobserver Reliability
Authors: Bluemke David A. , Krupinski Elizabeth A. , Ovitt Theron , Gear Kathleen , Unger Evan , Axel Leon , Boxt Lawrence M. , Casolo Giancarlo , Ferrari Victor A. , Funaki Brian , Globits Sebastian , Higgins Charles B. , Julsrud Paul , Lipton Martin , Mawson John , Nygren Anders , Pennell Dudley J. , Stillman Arthur , White Richard D. , Wichter Thomas , Marcus Frank
Published: June 2003

Background: Magnetic resonance (MR) imaging is frequently used to diagnose arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D). However, the reliability of various MR imaging features for diagnosing ARVC/D is unknown. The purpose of this study was to determine which morphologic MR imaging features have the greatest interobserver reliability for diagnosing ARVC/D. Methods: Forty-five sets of films of cardiac MR images were sent to 8 radiologists and 5 cardiologists with experience in this field. There were 7 cases of definite ARVC/D as defined by the Task Force criteria. Six cases were controls. The remaining 32 cases had MR imaging because of clinical suspicion of ARVC/D. Readers evaluated the images for the presence of (a) right ventricle (RV) enlargement, (b) RV abnormal morphology, (c) left ventricle enlargement, (d) presence of high T1 signal (fat) in the myocardium, and (e) location of high T1 signal (fat) on a Likert scale with formatted responses. Results: Readers indicated that the Task Force ARVC/D cases had significantly more (χ2 = 119.93, d.f. = 10, p < 0.0001) RV chamber size enlargement (58%) than either the suspected ARVC/D (12%) or no ARVC/D (14%) cases. When readers reported the RV chamber size as enlarged they were significantly more likely to report the case as ARVC/D present (χ2= 33.98, d.f. = 1, p < 0.0001). When readers reported the morphology as abnormal they were more likely to diagnose the case as ARVC/D present (χ2 = 78.4, d.f. = 1, p < 0.0001), and the Task Force ARVC/D (47%) cases received significantly more abnormal reports than either suspected ARVC/D (20%) or non-ARVC/D (15%) cases. There was no significant difference between patient groups in the reported presence of high signal intensity (fat) in the RV (χ2 = 0.9, d.f. = 2, p > 0.05). Conclusions: Reviewers found that the size and shape of abnormalities in the RV are key MR imaging discriminates of ARVD. Subsequent protocol development and multicenter trials need to address these parameters. Essential steps in improving accuracy and reducing variability include a standardized acquisition protocol and standardized analysis with dynamic cine review of regional RV function and quantification of RV and left ventricle volumes.
Use of Reconstructed, Non-Orthogonal Plane, High-Resolution Computed Tomography of the Temporal Bone in the Planning of Temporal Bone Surgery
Authors: Manolidis Spiros , Williamson Bobby , Chan Ling-Ling , Taber Katherine H. , Hayman L. Anne
Published: June 2003

Objectives: To demonstrate the utility of high-resolution computed tomography (HRCT) reconstructed in non-orthogonal planes in the planning of temporal bone surgery. Study Design: Qualitative and quantitative comparison of in vivo anatomic measurements between orthogonal and non-orthogonal plane reformatted HRCT of the temporal bone. Methods: HRCT data of 10 normal temporal bones were reconstructed two-dimensionally in two non-orthogonal planes. Parallel to the plane defined by the superior semicircular canal (defined as transverse) as well as perpendicular to the plane defined by the superior semicircular canal (defined as longitudinal). This was done using commercially available software. Sixteen surgically important relationships between neural, vascular and/or bony structures were measured and analyzed. Results: Quantitatively, wide variations were obtained in the measurements obtained from images of both non-orthogonal planar orientations. These variations were not age or sex dependent. Qualitatively, the images obtained highlight the anatomy of the temporal bone and skull base as it will be encountered during otologic surgery, since the surgical visual axis is along the long axis of the temporal bone. Conclusions: The reformatted images in non-orthogonal planes were superior to the axial and coronal series because they condensed critical relationships into a single perspective which promoted an intuitive understanding of the surgical approach. These reconstructed images show wide differences in quantitative measurements between surgically relevant landmarks. The protocol can be easily implemented in the clinical setting and is a potentially valuable educational tool. We recommend that non-orthogonal reconstructed images be routinely included with orthogonal temporal bone HRCT scans.
Results of Magnetic Resonance Imaging Assessment, Acoustic Analysis, Phonatory Function and Perceptual Rating of Glottic Insufficiency before and after Fat Augmentation: Correlated with Subjective Rating
Authors: Hsiung Ming-Wang , Chen Yen-Yu , Pai Lu , Lin Chao-Jung , Wang Hsing-Won
Published: June 2003

Autogenous fat augmentation has been proven effective in the treatment of glottic insufficiency (GI) using both subjective and objective methods of evaluation. However, no information is available in published research regarding the effectiveness and predictability of value parameters with regard to patients’ perceptions and concerns. This article retrospectively examines the correlation between subjective and objective examinations and subjective ratings (SRs) in patients with presbylaryngis (n = 14) and sulcus vocalis (n = 2). Acoustic analysis, phonatory function, magnetic resonance imaging (MRI) assessment, and perceptual rating data were evaluated against SRs using pre- and postoperative test results in 16 patients. The mean time over which subjective and objective examinations were performed was 10 months. Twelve patients reported excellent results, while no change was observed in 4 patients. When compared against SR, the kappa value of jitter, shimmer, harmonic to noise ratio, phonation time, grade, roughness, breathiness, and MRI were 0.25, 0, –0.08, –0.11, –0.11, 0.18, 0, and 1, respectively. The agreement between the MRI and SR values was complete, and was the only relationship shown to be significant (p < 0.001). MRI assessment is an effective and reliable examination tool which can be considered for use in assessing the progress of the post-fat injection operation in GI patients during follow-up examinations. Furthermore, due to the excellent agreement between MRI assessment and the patients’ subjective feelings, the SR value may serve as a good index of fat survival.
Labyrinth Anesthesia – A Forgotten but Practical Treatment Option in Ménière’s Disease
Authors: Adunka Oliver , Moustaklis Elena , Weber Alexander , May Angelika , von Ilberg Christoph , Gstoettner Wolfgang , Kierner Antonius C.
Published: June 2003

The aim of this study was to determine the efficiency of labyrinth anesthesia – the intratympanic instillation of lidocaine – in the treatment of Ménière’s disease and to recall a forgotten method. Twenty-four patients (15 male, 9 female), aged from 19.7 to 80.6 years (mean: 47.8 years) with the clinical diagnosis of unilateral Ménière’s disease who underwent labyrinth anesthesia in our department were included in this retrospective study. After local anesthesia of the tympanic membrane, a solution of 4% lidocaine and furfuryladenine (Kinetin) was instilled into the tympanic cavity. Patient records, a questionnaire and a physical examination were used to evaluate vertigo control, hearing loss, tinnitus, and quality of life according to the AAO-HNS criteria before and after surgery. Postoperatively, 87.5% of patients reported at least a noticeable decrease of vestibular symptoms, 66.7% of these patients were free of attacks for an average of 26.5 months. Postoperative hearing was the same or even improved in 87.5% of our patients. Tinnitus was not affected in any individual. Based on the findings presented herein, we consider labyrinth anesthesia a practicable and, due to its safety, highly recommendable therapeutic option for patients suffering from Ménière’s disease.
Assessment of Auditory Skills in 140 Cochlear Implant Children Using the EARS Protocol
Authors: Sainz Manuel , Skarzynski Henryk , Allum John H.J. , Helms Jan , Rivas Adriana , Martin Jane , Zorowka Patrick Georg , Phillips Lucy , Delauney Joseph , Brockmeyer Steffi Johanna , Kompis Martin , Korolewa Inna , Albegger Klaus , Zwirner Petra , Van de Heyning Paul , D’Haese Patrick
Published: June 2003

Auditory performance of cochlear implant (CI) children was assessed with the Listening Progress Profile (LiP) and the Monosyllabic-Trochee-Polysyllabic-Word Test (MTP) following the EARS protocol. Additionally, the ‘initial drop’ phenomenon, a recently reported decrease of auditory performance occurring immediately after first fitting, was investigated. Patients were 140 prelingually deafened children from various clinics and centers worldwide implanted with a MEDEL COMBI 40/40+. Analysis of LiP data showed a significant increase after 1 month of CI use compared to preoperative scores (p < 0.01). No initial decrease was observed with this test. Analysis of MTP data revealed a significant improvement of word recognition after 6 months (p < 0.01), with a significant temporary decrease after initial fitting (p < 0.01). With both tests, children’s auditory skills improved up to 2 years. Amount of improvement was negatively correlated with age at implantation.
Vestibular Morphology in the Mutant Mix-Mouse
Authors: Sato Harushiro , Bagger-Sjöbäck Dan , Hultcrantz Malou
Published: June 2003

Mix-mice, a new strain of mice with inner ear dysfunction, and their littermates were used in the present study in order to investigate vestibular morphology, visualised by light microscopy (LM) and transmission electron microscopy (TEM). Contrary to the mix-mice, their littermates showed less stained nerve chalices and it was possible to detect that hair cells showed surface herniations and so-called ‘blebs’ in the apical portion of the epithelium. Sensory hairs showed a disarrayed pattern. The mix-mice had severe microscopical abnormalities: collapse of the membranous cell layer, cavities inside the neuroepithelium, severe loss of hair cells, herniations of the few remaining hair cells and increased supporting cells were evident. In the utricle and saccule, hair cells were missing and the epithelial surface was covered by a single layer of smooth, flattened epithelial cells of hitherto unknown origin.
Nasal Septal Perforations during Treatment with Topical Nasal Glucocorticosteroids Are Generally Not Associated with Contact Allergy to Steroids
Authors: Cervin Anders , Hansson Christer , Greiff Lennart , Andersson Morgan
Published: June 2003

Background: Mucosal ulcers and perforations of the nasal septum are very rare and may have several underlying causes. Contact allergy to steroids has been suggested as a possible aetiological factor in patients who develop perforations during topical steroid use. Methods: We have identified 13 subjects with perforations of their nasal septum and concomitant topical nasal steroid use. In order to evaluate whether these patients had developed contact allergy to steroids they underwent patch testing with an extended steroid series. Results: None of the subjects displayed any positive reaction to the steroids. Conclusion: Sensitivity to glucocorticoids is a well-described phenomenon and may in selected subjects also be associated with local side effects to nasal sprays. However, contact allergy to steroids does not seem to be a general explanation for septal perforations in patients using nasal steroids.
Microbiology and Management of Deep Facial Infections and Lemierre Syndrome
Authors: Brook Itzhak
Published: June 2003

This review describes the microbiology, diagnosis and management of deep facial infections and Lemierre syndrome. The origins of most of these infections are odontogenic infections that spread to fascial spaces of the lower head and upper neck. Other sources include pharyngotonsillar, nasal, otologic, salivary gland and dermatologic infections, hematogenic spread, cervical adenitis and trauma. These space infections can be divided into those around the face (masticatory, buccal, canine and parotid), the suprahyoid area (submandibular, sublingual and lateral pharyngeal) and the infrahyoid region or lateral neck (retropharyngeal and pretracheal spaces). The organisms accounting for these infections are aerobic and anaerobic that arise from the oropharyngeal flora. Complications of these infections can be life threatening and can result from hematogenic or direct spread. Complications that arise following local extension include suppurative jugular thrombophlebitis, cavernous sinus thrombosis, carotid erosion, maxillary sinusitis and osteomyelitis of the jaws. Management includes surgical drainage and antimicrobial therapy.
Pituitary Apoplexy: A Pathologic Entity from an Otolaryngologist’s View
Authors: Xenellis J. , Stivaktakis J. , Karpeta N. , Rologis D. , Ferekidis E.
Published: June 2003

A case of pituitary apoplexy, which was initially misdiagnosed as ‘acute frontal sinusitis’, is reported. The presenting symptoms and signs of the patient were headache, moderate fever, left periorbital edema, marked tenderness over the left frontal sinus and purulent secretion over the left middle turbinate and nasopharynx. These clinical symptoms were wrongly perceived as complicated frontal sinusitis. The CT scan and the elective right carotid angiography showed a pituitary adenoma. Therefore pituitary apoplexy of a preexisting pituitary adenoma was diagnosed. The patient underwent surgical removal of the adenoma and his postoperative course was uneventful. Thus otolaryngologists should consider pituitary apoplexy in the differential diagnosis of pathologies concerning the anatomic area of the anterior cranial fossa.
Changes in the Tullio Phenomenon and the Fistula Sign in the Course of Endolymphatic Hydrops
Authors: Suzuki Mitsuya , Kitajima Naoharu , Ushio Munetaka , Shintani Mieko , Ishibashi Toshio
Published: June 2003

We performed electronystagmography with caloric stimulation and studied vestibular evoked myogenic potentials (VEMPs) associated with changes in the Tullio phenomenon and the fistula sign during the clinical course of a patient with endolymphatic hydrops. The Tullio phenomenon and the fistula sign disappeared in association with a reduction in the caloric response, which implicates the ampullary function of the lateral semicircular canal. Even when no VEMP could be detected for the affected ear, the Tullio phenomenon and fistula signs were observed; thus, either these phenomena had a lower response threshold than the VEMPs, or saccular receptors were not involved in the Tullio phenomenon.
Silicone Septal Button in the Management of a Large Tracheo-Oesophageal Fistula following Primary Puncture in a Laryngectomee
Authors: Mirza S. , Head M. , Robson A.K.
Published: June 2003

We describe the use of a silicone septal button in the management of a patient who developed a large tracheo-oesophageal fistula following primary puncture as part of a total laryngectomy. The button was easily inserted, well tolerated and prevented leakage of solids into the trachea, allowing the patient to eat.
Cerebral Correlates of the Progression Rate of the Cognitive Decline in Probable Alzheimer’s Disease
Authors: Nagahama Yasuhiro , Nabatame Hidehiko , Okina Tomoko , Yamauchi Hiroshi , Narita Minoru , Fujimoto Naoki , Murakami Motonobu , Fukuyama Hidenao , Matsuda Minoru
Published: June 2003

Objective: To evaluate the possible relation between the rate of cognitive deterioration in patients with probable Alzheimer’s disease (AD) and the distribution pattern of neural dysfunction. Methods: The regional cerebral blood flow (rCBF) was measured in rapidly and slowly progressing groups of AD patients using single-photon emission computed tomography and was compared between the groups. While controlling for demographic and clinical factors that could be associated with the stage and prognosis of the illness, the deterioration rate of the Mini Mental State Examination (MMSE) score was significantly greater in the rapidly progressing group than that in the slowly progressing group. Results: The rCBF in the right posterodorsal, anterior and superior prefrontal cortices and the inferior parietal cortex was significantly lower in the rapidly progressing patients. Moreover, lower perfusion in these regions correlated significantly with rapid deterioration in the MMSE. Conclusions: These findings suggest that the rCBF values in these cortical regions could be useful in predicting which AD patients will show a relatively rapid cognitive decline.
Successful Treatment of Dermatomyositis and Polymyositis with Anti-Tumor-Necrosis-Factor-Alpha: Preliminary Observations
Authors: Hengstman G.J.D. , van den Hoogen F.H.J. , Barrera P. , Netea M.G. , Pieterse A. , van de Putte L.B.A. , van Engelen B.G.M.
Published: June 2003

Tumor necrosis factor α neutralization seems a rational therapy for myositis because this proinflammatory cytokine has been implicated in the pathogenesis of this disorder. Until now, we have treated 2 patients with a chimeric anti-TNF-α monoclonal antibody (infliximab). Both patients demonstrated a marked and sustained subjective and objective improvement without the occurrence of any side effects. These preliminary results suggest that anti-TNF-α treatment with infliximab is a safe and rapidly effective therapy for myositis.
Quality of Life after Vagus Nerve Stimulation for Intractable Epilepsy: Is Seizure Control the Only Contributing Factor?
Authors: McLachlan Richard S. , Sadler Mark , Pillay Neelan , Guberman Alan , Jones Michael , Wiebe Samuel , Schneiderman Jack
Published: June 2003

We assessed the impact of vagus nerve stimulation on a cohort of patients with intractable epilepsy. A 1-year prospective trial of vagus nerve stimulation for intractable epilepsy was done in 26 patients. Seizure frequency, anti-epileptic drugs, and quality of life were assessed using QOLIE-89, ELDQOL, and a Likert scale of impact of treatment. Seizures were reduced by more than 50% in 19% of the patients, by less than 50% in 46%, and were unchanged in 35% of them. Antiepileptic drugs were reduced in 43% of the patients. There was a significant improvement in the mean overall QOLIE-89 score and other measures of quality of life, but these did not correlate with changes in seizure frequency. Subjective improvement occurred in 84% of the patients. The quality of life improves in some patients following vagus nerve stimulation for intractable epilepsy. The favorable effects of this treatment may be attributable to additional factors besides seizure control which in this study was modest.
DNA Testing for Huntington Disease in the Turkish Population
Authors: Akbas Fahri , Erginel-Unaltuna Nihan
Published: June 2003

Huntington disease (HD) is an autosomal dominant inherited disease, characterized by involuntary movements, behavioral and personality changes and dementia. Although the mean age at onset is about 40 years, onset varies from 5 to 79 years. Therefore, at-risk individuals are never sure to have escaped the disease. The genetic defect is a CAG trinucleotide repeat expansion at the 5′ end of the IT-15 gene on chromosome 4. In this study, we analyzed 127 patients with HD and 122 healthy controls. The numbers of CAG repeats varied from 38 to 78 (median: 42) in 127 HD patients, while in healthy controls we observed only 10–35 CAG repeats (median: 18). The length of the CAG repeat expansion in Turkish HD patients and normal controls was similar to that reported from other populations. Negative correlations (r = –0.67) were also found between age of disease onset and repeat length.
Decreased Frequency of the Tumor Necrosis Factor α –308 Allele in Serbian Patients with Multiple Sclerosis
Authors: Drulović Jelena , Popadić Dušan , Mesaroš Šarlota , Dujmović Irena , Cvetković Ivana , Miljković Djordje , Stojsavljević Nebojša , Pravica Vera , Pekmezović Tatjana , Bogdanović Gradimir , Jarebinski Mirjana , Stojković Marija Mostarica
Published: June 2003

Tumor necrosis factor (TNF) α has been considered the prototypic cytopathogenic cytokine in multiple sclerosis (MS), but recently this cytokine has been shown to possess significant anti-inflammatory and neuroprotective effects in demyelinating diseases. It has been reported that the TNFα –308 polymorphism influences levels of TNFα production, and that the rare allele, TNF2, is associated with high TNFα production. We investigated the TNFα –308 polymorphism in 143 unrelated Serbian patients with MS and 123 ethnically matched, healthy individuals using the allele-specific restriction fragment length polymorphism polymerase chain reaction technique. The frequency of the TNF2 allele was significantly decreased in MS patients (14%) in comparison with controls (24%; p = 0.044). The TNF2 allele had no influence on disease behavior, since it was not associated with the course and severity of MS in this group of patients. The result suggests that in the Serbian population polymorphism at position –308 of TNFα or at an adjacent locus might have a role in MS susceptibility.
Assessment of Neuroinflammation and Microglial Activation in Alzheimer’s Disease with Radiolabelled PK11195 and Single Photon Emission Computed Tomography
Authors: Versijpt Jan J. , Dumont Filip , van Laere Koen J. , Decoo Danny , Santens Patrick , Audenaert Kurt , Achten Eric , Slegers Guido , Dierckx Rudi A. , Korf Jakob
Published: June 2003

Objectives: Inflammation contributes to degeneration in Alzheimer’s disease (AD), not simply as a secondary phenomenon, but primarily as a significant source of pathology. [123I]iodo-PK11195 is a single photon emission computed tomography (SPECT) ligand for the peripheral benzodiazepine receptor, the latter being expressed on microglia (brain resident macrophages) and upregulated under inflammatory circumstances. The objectives were to assess AD inflammation by detecting [123I]iodo-PK11195 uptake changes and investigate how uptake values relate with perfusion SPECT and neuropsychological findings. Methods: Ten AD and 9 control subjects were included. [123I]iodo-PK11195 SPECT images were realigned into stereotactic space where binding indices, normalized on cerebellar uptake, were calculated. Results: The mean [123I]iodo-PK11195 uptake was increased in AD patients compared with controls in nearly all neocortical regions; however, statistical significance was only reached in the frontal and right mesotemporal regions. Significant correlations were found between regional increased [123I]iodo-PK11195 uptake and cognitive deficits. Conclusions: [123I]iodo-PK11195 is a cellular disease activity marker and allows in vivo assessment of microglial inflammation in AD.
Clinical Presentation and Treatment of Wilson’s Disease: A Single-Centre Experience
Authors: Pellecchia M.T. , Criscuolo C. , Longo K. , Campanella G. , Filla A. , Barone P.
Published: June 2003

Thirty patients with Wilson’s disease (WD) were observed at a movement disorder clinic between 1970 and 2000. Disease onset was at the mean age (SD) of 14.5 (±5.9) years. Presentation with hepatic disease occurred in 12 of 30 patients and with neurologic disease in 15. Three patients were asymptomatic at the time of diagnosis. The mean (SD) delay to diagnosis was 5.9 (±5.7) years. Five patients diagnosed in an advanced stage of disease died before initiating treatment. Eighteen patients were followed and treated with D-penicillamine alone or in combination with zinc sulphate. Treatment improved most of neurological symptoms. Dystonic postures, behavioural disturbances and dysarthria were the most resistant neurological signs. ‘Pseudo-sclerotic’ neurologic involvement predicted a good outcome, whereas hepatic onset and ‘classic’ neurologic involvement were associated with a poorer prognosis. Two of the 18 treated patients died of hepatic failure due to voluntary discontinuation of therapy. Both D-penicillamine and zinc sulphate were well tolerated. No teratogenic effect of D-penicillamine was observed throughout 5 pregnancies. Our results suggest that D-penicillamine or a combination of D-penicillamine and zinc sulphate is a safe and effective long-term treatment in patients with WD.
Atrophy of the Substantia innominata on Magnetic Resonance Imaging Predicts Response to Donepezil Treatment in Alzheimer’s Disease Patients
Authors: Tanaka Yuriko , Hanyu Haruo , Sakurai Hirofumi , Takasaki Masaru , Abe Kimihiko
Published: June 2003

To investigate whether atrophy of the substantia innominata as shown on magnetic resonance imaging (MRI), reflecting degeneration of cholinergic neurons in the nucleus basalis of Meynert, predicts response to donepezil treatment in patients with Alzheimer’s disease (AD), we studied correlations between the thickness of the substantia innominata and clinical efficacy. Eighty-two patients were divided into responders, including transiently and continuously responding groups, and nonresponders, based on the changes in the Mini-Mental State Examination (MMSE) score from baseline at 3 months and at 12 months. Atrophy of the substantia innominata was more pronounced in transiently and continuously responding groups than nonresponders, but no significant change in the thickness between transiently and continuously responding groups was found. The MMSE score changes from baseline at 3 months and at 12 months significantly inversely correlated with the thickness of the substantia innominata. Logistic regression analysis revealed that the overall discrimination rate with the thickness of the substantia innominata was 70% between responders and nonresponders. We conclude that atrophy of the substantia innominata on MRI helps to predict response to donepezil treatment in patients with AD.
Inflammatory Markers in Matched Plasma and Cerebrospinal Fluid from Patients with Alzheimer’s Disease
Authors: Sun Yong-Xin , Minthon L. , Wallmark A. , Warkentin S. , Blennow K. , Janciauskiene S.
Published: June 2003

It has been suggested that a number of molecules associated with inflammation are involved in the pathogenesis of Alzheimer’s disease (AD). We measured the levels of α1-antichymotrypsin (ACT), α1-antitrypsin (AAT), interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1) and oxidised low-density lipoprotein (oxLDL) in matched cerebrospinal fluid (CSF) and plasma of 141 patients with probable AD. We found a significant relationship between CSF and plasma levels of ACT (r = 0.4, p < 0.001), IL-6 (r = 0.74, p < 0.001), MCP-1 (r = 0.71, p < 0.001), and a borderline relationship between CSF and plasma oxLDL (r = 0.22, p < 0.05). In addition, linear regression analysis revealed a positive correlation between levels of CSF-ACT and oxLDL (p < 0.001), but an inverse relation between levels of CSF ACT, CSF AAT and MCP-1 (p < 0.001). A significant correlation was also found between levels of CSF ACT, oxLDL and the ratio of CSF to serum albumin, which is used as a measure of the blood-brain barrier function. Our data extend previous reports regarding the inflammatory markers in the plasma and CSF of patients with AD and provide good evidence that levels of ACT, IL-6, MCP-1 and oxLDL in plasma and CSF might be candidates as biomarkers for monitoring the inflammatory process in AD.
Vitamin B12-B6-Folate Treatment Improves Blood-Brain Barrier Function in Patients with Hyperhomocysteinaemia and Mild Cognitive Impairment
Authors: Lehmann Martin , Regland Björn , Blennow Kaj , Gottfries C.G.
Published: June 2003

Thirty patients had mild cognitive impairment and increased homocysteine levels in serum. On average, they were supplemented orally with a high dose of a vitamin B12-B6-folate combination for 270 days. All patients had normal serum B12 and folate levels at baseline. Cerebrospinal fluid levels of the tau protein (CSF-tau) and the albumin ratio were measured before and after treatment. The serum homocysteine levels were normalised after treatment. The albumin ratio significantly correlated with vascular risk factors. At baseline, the ratio was higher in the patients in comparison with age-matched controls. After treatment, the ratio was significantly reduced, which may indicate a tightening of the blood-brain barrier. The CSF-tau levels did not change significantly although there was a numeric decline. None of the patients progressed into dementia during the treatment period. When treated with a vitamin B12-B6-folate combination, patients with mild cognitive impairment and hyperhomocysteinaemia appear to improve their blood-brain barrier function. They may also stabilise their cognitive status. Further investigations are warranted on the role of blood-brain barrier dysfunction in the pathogenesis of dementia.
Cathepsin D Polymorphism in Italian Elderly Subjects with Sporadic Late-Onset Alzheimer’s Disease
Authors: Ingegni Tiziana , Nocentini Giuseppe , Mariani Elena , Spazzafumo Liana , Polidori M. Cristina , Cherubini Antonio , Catani Marco , Cadini Donatella , Senin Umberto , Mecocci Patrizia
Published: June 2003

Alzheimer’s disease (AD) is the most frequent cause of dementia in elderly people. Different pathological pathways have been involved in the development of late-onset AD. Among them, numerous genes have been proposed as pathogenetic factors acting independently or interactively. It has been suggested that the cathepsin D gene (CTSD) is associated with late-onset AD. We analyzed an exonic polymorphism of the CTSD gene [C→T (Ala→Val) transition at position 224] in 142 AD patients and 120 controls. Our data indicate no significant association between this polymorphism and the risk of AD. Likewise there was no association between CTSD polymorphism and the apolipoprotein E genotype in the risk of developing AD.
The Impact of Different Diagnostic Criteria on Prevalence Rates for Delirium
Authors: Laurila Jouko V. , Pitkala Kaisu H. , Strandberg Timo E. , Tilvis Reijo S.
Published: June 2003

A cross-sectional study was performed to evaluate the concordance of the present criteria of delirium among elderly (>70 years) geriatric hospital patients (n = 230) and nursing home residents (n = 195). Different subjects were diagnosed as having delirium when operationalized criteria according to the American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders (DSM-III, DSM-III-R, DSM-IV) and the World Health Organization’s International Classification of Diseases (ICD-10) were used. Whereas 132 subjects (31.1%) met the criteria for delirium by at least 1 classification, only 25 (5.9%) met all 4. The most inclusive was the DSM-IV (24.9% of the subjects) followed by DSM-III-R (19.5%), DSM-III (18.8%) and ICD-10 (10.1%), respectively. The DSM-IV and ICD-10 had the largest number of patients not overlapping with any other diagnostic group. The newest DSM-IV classification found more cases of delirium especially among acutely ill, hospitalized patients.
Volume Reduction in Cerebral Blood Flow in Patients with Alzheimer’s Disease: A Sonographic Study
Authors: Maalikjy Akkawi N. , Borroni B. , Agosti C. , Pezzini A. , Magoni M. , Rozzini L. , Prometti P. , Romanelli G. , Vignolo L.A. , Padovani A.
Published: June 2003

Neuroimaging techniques such as PET and SPECT demonstrated a consistent reduction of cerebral blood flow (CBF) in Alzheimer’s disease (AD). The aim of the study was to assess the potential role of ultrasonography for CBF measurement in AD patients and whether the CBF volume correlates positively with disease severity. Fifty patients who met the diagnostic criteria of probable AD (NINDS-ADRDA) were compared to 50 age-matched healthy elderly volunteers. The extracranial internal carotid arteries (ICAs) and the vertebral arteries (VAs) of the patients and controls were examined. Angle-corrected time-averaged flow velocity (TAV) and the diameter of the vessel were measured. Intravascular flow volumes were calculated as the product of TAV and the cross-sectional area of the circular vessel. CBF volume was calculated as the sum of flow volumes in the ICAs and VAs of both sides. All subjects underwent the MMSE. The mean global CBF (474.87 ± 94.085 vs. 744.26 ± 94.082 ml/min; p < 0.0001) was lower in AD patients than in healthy volunteers. A significant decline in global flow volumes (r = 0.48; p < 0.0007) with the degree of cognitive impairment was also present. The ability of ultrasonography to characterize flow decreases makes such a technique an attractive tool for the study of AD, for the evaluation of pharmacological therapies and, possibly, for early diagnosis.
The Validity and Reliability of 6 Sets of Clinical Criteria to Classify Alzheimer’s Disease and Vascular Dementia in Cases Confirmed Post-Mortem: Added Value of a Decision Tree Approach
Authors: Hogervorst E. , Bandelow S. , Combrinck M. , Irani S.R. , Smith A.D.
Published: June 2003

Data from 204 participants from the Oxford Project to Investigate Memory and Ageing, who were diagnosed post-mortem using the histopathological criteria of the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD), were used to assess the validity of the clinical criteria for Alzheimer’s disease (AD) of the ‘National Institute of Neurological and Communicative Disorders and Stroke/the Alzheimer’s Disease and Related Disorders Association’ (NINCDS/ADRDA). Cases who had been diagnosed as NINCDS/ADRDA ‘probable AD’ in life were usually confirmed at autopsy, but half of the NINCDS/ADRDA ‘negative’ cases were not (low specificity). It was hypothesized that the overall clinical impression may have taken precedence over the use of the actual criteria. We therefore investigated the validity and reliability of the clinical criteria using a computerized ‘dementia diagnosis system’ for each of 6 sets of criteria [Diagnostic and Statistical Manual of Mental Disorders (DSM-IV), NINCDS/ADRDA and three sets of criteria specifically for vascular dementia (VaD): NINCDS-AIREN, State of California Alzheimer’s Disease Diagnostic and Treatment Centers (ADDTC), and Vascular Cognitive Impairment (VCI)] to classify a subset (n = 96) of the cases confirmed post-mortem. The use of the computerized system significantly (p = 0.01) increased the specificity (81%, similar to sensitivity) of the NINCDS/ADRDA diagnoses, which were shown to have ‘moderate’ inter-rater reliability. The DSM-IV criteria had good validity for AD when compared with post-mortem confirmation and showed ‘substantial’ inter-rater reliability. The ADDTC and VCI criteria for VaD had good specificity (88%) and sensitivity (75%), but only for one rater. The DSM-IV and NINCDS-AIREN criteria for VaD showed poor validity and inter-rater reliability. We conclude that the forced use of decision trees through a computerized system enhances the accuracy of the clinical diagnoses of dementia.
Molecular genetic delineation of a deletion of chromosome 13q12→q13 in a patient with autism and auditory processing deficits
Authors: Smith M. , Woodroffe A. , Smith R. , Holguin S. , Martinez J. , Filipek P.A. , Modahl C. , Moore B. , Bocian M.E. , Mays L. , Laulhere T. , Flodman P. , Spence M.A.
Published: June 2003

In a sporadic case of autism and language deficit due to auditory processing defects, molecular genetic studies revealed that a chromosomal deletion occurred in the 13q12→q13 region. No chromosome abnormalities were detected in the parents. We determined that the deletion occurred on the paternally derived chromosome 13. There are two previous reports of chromosome 13 abnormalities in patients with autism. The deletion in the subject described in this paper maps between the two chromosome 13 linkage peaks described by Bradford et al. (2001) in studies of subjects with autism and language deficits. The 9-Mb region deleted in the patient described here contains at least four genes that are expressed in brain and that play a role in brain development. They are NBEA, MAB21L1, DCAMKL1 and MADH9. These genes therefore represent candidate genes for autism and specific language deficits.
Increased frequency of X-bearing sperm in males from an infertility clinic: analysis by two-color fluorescence in situ hybridization
Authors: Johannisson R. , Leuschner E. , Hüppe M. , Hinrichs F. , Al-Hasani S. , Diedrich K. , Schwinger E. , Mennicke K.
Published: June 2003

Semen samples from 34 men visiting the Lübeck infertility clinic were investigated using a two-color FISH method to determine the ratio of X- and Y-bearing sperm. The overall ratio was significantly shifted to a preponderance of X-containing sperm. A statistical comparison with seven reports from the literature which included 53 normal probands demonstrated in our patients a significant tendency of a preponderance of X-bearing sperm and significantly less Y-bearing sperm. Furthermore, the Lübeck sperm samples are remarkably more heterogeneous in respect to their variability of X- and Y-bearing spermatozoa than in the other mentioned studies with normal probands. These phenomena have to be evaluated in further studies on groups of infertile males showing similar infertility histories.
Genomic organization of human TCF12 gene and spliced mRNA variants producing isoforms of transcription factor HTF4
Authors: Gan T.-I. , Rowen L. , Nesbitt R. , Roe B.A. , Wu H. , Hu P. , Yao Z. , Kim U.-J. , O’Sickey T. , Bina M.
Published: June 2003

The human TCF12 gene, mapping to 15q21, encodes the helix-loop-helix transcription factor 4 (HTF4). A detailed analysis of this genomic region established the organization of the TCF12 gene. The gene includes 21 exons and is significantly larger than an average human gene. Preceding the second exon, two alternative acceptor sites for mRNA splicing yield two distinguishable transcripts (HTF4a and HTF4b) which differ in their 5′ untranslated region but share identical coding sequences. Differential utilization of exon 15 in the TCF12 gene may reflect a mechanism producing a cell-type-specific protein (HTF4c). In addition, intron 5 in the TCF12 gene corresponds to the region involved in a translocation, t(9;15)(q22;q21), that results in a form of extraskeletal myxoid chondrosarcoma.
Identification and characterization of Srsp1, a rat gene differentially expressed during spermatogenesis and coding for a serine stretch-containing protein
Authors: Geisinger A. , Dos Santos A. , Benavente R. , Wettstein R.
Published: June 2003

By means of mRNA differential display and cDNA library screening we have characterized a novel gene of the rat that is differentially expressed during spermatogenesis. Northern blot analyses showed that its mRNA reaches the highest level during the first meiotic prophase. The transcript appears to be testis-specific as it was not detectable in any of the nine other tissues tested. The full length ORF encodes a putative phosphoprotein containing a serine stretch and a bipartite nuclear localization signal, which we call Srsp1 (“serin-rich spermatogenic protein 1”). Comparison of the cDNA from Srsp1 with genomic sequences in databases allowed us to determine the number of introns; some putative regulatory sequences are proposed. This is the first report of a gene differentially expressed during spermatogenesis that codes for a protein containing a serine stretch.