bluuebunny/crossref_metadata_2025 huggingface dataset:
Shortening of the Front Vibrating Part of the Vocal Folds in Phonation
Authors: Pešák J. , Jindra P.
Published: January 2005

We have tried to make use of the opportunity of repeated observations through the analysis of the recorded movements of the phonating vocal folds by means of the phonating vocal folds through indirect videolaryngostroboscopic technique. The results of our investigation correspond, among others, with Hála and Sovák’s diagrammatic description of continual and gradual changes in the vibration of the vocal folds in an uninterrupted sequence of tones of the human voice. In the initial chapter mention has been made of Hála and Honty’s works and of Pressmann’s work dealing with the described behaviour of the glottis when phonating high-pitched tones. The conclusions analogous to our findings have also been described by means of stereoscopically measuring the length of the phonating vocal folds. In conclusion, by measuring the distances between the anterior commissure and the junction between the membranous part of the vocal fold and vocal process of the arytenoid and the anterior commissure to the posterior nodal point of the vibrating part of the vocal folds we have verified the correctness of the findings published by Czermak, Hála and Honty, Pressmann, and Sovák, who pointed out the phenomenon of the shortening of the front vibrating part of the vocal folds in phonating high-pitched tones of the human voice.
Morphometric Quantification of Apoptotic Stages in Cell Culture
Authors: Sabbatini Maurizio , Bozzo Chiarella , Castellucci Mario , Cannas Mario
Published: January 2005

Apoptosis is an active process of self-destruction, whereby cells undergo physiological cell death. It occurs during development and regulation of tissue homeostasis or as a result of changes in environmental stimuli. Chromatin condensation and nuclear fragmentation, which are typical features of apoptotic nuclei, are usually quantified by fluorescent DNA dyes. The present study reports a reliable method to analyze morphological apoptotic stages in cultured cells, using light microscopy. We used the human neuroblastoma cell line SK-N-BE as a model to study apoptosis induced by inadequate cell-matrix interactions. Apoptosis was detected on cells cultured for different time intervals on polyHEMA, poly-L-lysine or collagen I. Quantitative morphometric and densitometric analysis after hematoxylin nuclear staining and caspase-3 immunocytochemistry, as markers of occurring apoptosis, were performed. Our method identifies different stages of caspase-3 activation and the subsequent DNA fragmentation and condensation. This experimental procedure enables us to detect slight differences in apoptosis progression by morphological analysis.
Release Bursts in English Word-Final Voiceless Stops Produced by Native English and Korean Adults and Children
Authors: Tsukada Kimiko , Birdsong David , Mack Molly , Sung Hyekyung , Bialystok Ellen , Flege James
Published: January 2005

The aim of this study was to evaluate the acquisition of statistical properties ofa second language (L2). Stop consonants are permitted in word-final position inboth English and Korean, but they are variably released in English and invariablyunreleased in Korean. Native Korean (K) adults and children living in North Americaand age-matched native English (E) speakers repeated English words ending inreleased tokens of /t/ and /k/ at two times separated by 1.2 years. The judgments ofE-speaking listeners were used to determine if the stimuli were repeated with audiblerelease bursts. Experiments 1 and 2 revealed fewer final releases for K thanE adults, and fewer releases for /t/ (but not /k/) for K than E children. Nearly all /t/ and/k/ tokens were heard as intended in experiment 3, which evaluated intelligibility.However, the K adults’ /k/ tokens were identified with less certainty than theE adults’. Taken together, the results suggested that noncontrastive (i.e., statistical)properties of an L2 can be learned by children, and to a somewhat lesser extent byadults.
Underlying Voicing in Majorcan Catalan Word-Final Stop-Liquid Clusters
Authors: Recasens Daniel , Espinosa Aina , Solanas Antoni
Published: January 2005

This study investigates the extent to which phonetic voicing is maintained inword-final clusters composed of an underlying voiced stop followed by nonsyllabic/l/ or /r/ in Majorcan Catalan. Electropalatographic and acoustic data forfive speakers of this Catalan dialect reveal that, in agreement with the non-syllabicstatus of the liquid, voicing for /l/ is only available if occurring during the precedingstop. The rhotic is always phonetically voiceless. Speakers differ regarding theextent to which they keep the underlying stop voicing distinction and the productionstrategies they use for that purpose. This distinction is highly robust and distributedover the entire syllable in nasal-stop-/l/ clusters for some speakers, butmuch less clear or absent for those speakers who devoice /l/ as a general rule.Underlying stop voicing is cued primarily by stop closure duration and vocal foldvibration, or else by closure duration rather than by voicing. It may be concludedthat the word-final devoicing process operating in Catalan does not apply toMajorcan Catalan tautosyllabic stop clusters with a liquid, and that phonetic voicingmay affect just the stop or both the stop and the liquid. The implications ofthese findings for sound change are discussed.
Voice Register in Suai (Kuai): An Analysis of Perceptual and Acoustic Data
Authors: Abramson Arthur S. , L-Thongkum Theraphan , Nye Patrick W.
Published: January 2005

Analyses of the perceptual and acoustic characteristics of the Register 1(ʼclearʼ) versus Register 2 (ʼbreathyʼ) distinction have been carried out on the Kuaidialect of Suai, a Mon-Khmer language. The perception results were obtainedfrom five-parameter synthesized stimuli. They showed that the primary parameterunderlying the distinction is the frequency of onset of laryngeal excitation (F0).One other parameter making a significant contribution was the open quotient. TheF0 result was confirmed by an acoustic analysis of eight pairs of natural utterancesproduced by native speakers. We conclude that the Suai language is in a stateof flux with respect to the voice registers, although the distinction has not disappeared.The perceptual data reveal mixed levels of sensitivity, and the productiondata indicate that some speakers maintain a fairly good distinction, while othersdo not. The language seems to be replacing the register distinction with a prosodicone of pitch accent, possibly as a stage leading to tonogenesis.
Cellular Uptake of Vitamin B12 in Patients with Chronic Renal Failure
Authors: Obeid Rima , Kuhlmann Martin , Kirsch Carl-Martin , Herrmann Wolfgang
Published: January 2005

Background/Aims: Elevated concentration of plasma homocysteine (tHcy) is common in renal patients, however, the reason behind the resistance to vitamin B12 and folate therapy are poorly understood. Methods: We investigated vitamin B12 uptake by mononuclear cells (MC) from predialysis patients (n = 19) as compared to healthy controls (n = 15). Serum levels of tHcy, methylmalonic acid and cystathionine, holotranscobalamin (holoTC), total vitamin B12 and folate were also measured. Results: The uptake of vitamin B12 by MC from renal patients was lower than that by MC from controls (9.3 vs. 12.5 pg/3 × 106 cells; p = 0.001). Nonetheless, the receptor-binding capacity was comparable between patients and controls (6.1 vs. 6.5 pg/3 × 106 cells; p = 0.627). Average reduction of vitamin B12 uptake in patients as compared to the controls was 18.1%. Conclusions: Our results show that vitamin B12 uptake is impaired in MC from renal patients, with no evidence that the surface receptor is down-regulated. High serum concentrations of holoTC are common in renal patients and might be related to a generalized resistance to this vitamin. Serum concentrations of vitamin B12 within the reference range are not likely to ensure vitamin delivery into the cells. Supraphysiological doses of vitamin B12 may be necessary to deliver a sufficient amount of the vitamins to the cells via mechanisms largely independent of holoTC receptor.
Relationship of Urine Output to Dialysis Initiation and Mortality in Acute Renal Failure
Authors: Liangos Orfeas , Rao Madhumati , Balakrishnan Vaidyanathapuram S. , Pereira Brian J.G. , Jaber Bertrand L.
Published: January 2005

Background: A non-oliguric state is considered a good prognostic indicator in acute renal failure (ARF), and may lead to withholding renal replacement therapy in anticipation of recovery. The present study explores the relationship between urine volume and the start of dialysis and hospital mortality in patients with ARF. Methods: In a non-concurrent cohort of patients with ARF treated exclusively with intermittent hemodialysis (IHD), demographic, clinical and laboratory characteristics were collected at the time of the first nephrology consultation and at the start of dialysis. Multiple linear and logistic regression analyses were used to identify factors associated with the time to initiation of dialysis and hospital mortality, respectively. Results: Urine volume correlated with the time from admission to start of dialysis (r = 0.60; p < 0.001). Higher urine volume, lower serum creatinine and lower APACHE II score were independently associated with increased time from admission to start of dialysis. Hospital mortality was independently associated with a higher urine volume (odds ratio, OR 3.8, 95% confidence interval, CI, 1.1–12.8, p = 0.03), a higher MOF score (OR 4.9, 95% CI 1.1–21.6, p = 0.03) and a higher number of dialysis treatments performed in the 1st week (OR 3.7, 95% CI 1.2–11.3, p = 0.03). Conclusions: Among patients with ARF requiring IHD, increased urine output is associated with higher mortality. This observation may reflect physician bias toward later initiation of dialysis in non-oliguric ARF. Further research is needed to help identify patients with non-oliguric ARF who require early dialytic support.
Structural Changes in the Renal Vasculature in Streptozotocin-Induced Diabetic Rats without Hypertension
Authors: Joo Turoni Claudio M. , Reynoso Héctor A. , Marañón Rodrigo O. , Coviello Alfredo , Peral de Bruno María
Published: January 2005

Background/Aim: We evaluated in diabetic-streptozotocin rats (STZR) the structural changes of glomeruli, preglomerular vessels, glomerular tuft and renal parenchyma in order to determine the degree of renal injury and the presence of remodeling in afferent arterioles developed by diabetes without overimposed hypertension. Methods: Renal mass index and histological score (glomerular number, density, tubular lesions and degree of arteriosclerosis) were estimated. In afferent arterioles the ratio of wall thickness/lumen was obtained by stereological methods. Results: STZR developed diabetes without hypertension; renal mass index increased and matched changes in glomeruli (decrease of capillary number and enlargement of mesangium and basement capillary membrane). Both glomerular number and density as well as afferent arteriole number were diminished. Degenerative changes in both proximal (glycogenic and hyaline degeneration) and distal tubules (hyaline casts) were also observed. At variance with preglomerular vessels, the efferent arterioles only presented initial arteriosclerosis. Finally, the stereological study of afferent arterioles showed a significantly lower arteriolar lumen area and arteriolar wall thickness in STZR, resulting in a remodeling without modification of wall/lumen ratio. Conclusion: Diabetes, uncomplicated by hypertension, is associated with (1) a reduction in glomerular number; (2) degeneration in parenchyma and renal tubules, and (3) a specific pattern of remodeling in preglomerular vessels different from that induced by hypertension. Although this work demonstrated that these changes are not triggered by hypertension, further investigations are required in order to determine which mediators are involved in diabetic-vascular renal dysfunction.
Chronic Estradiol Exposure Modulates Thyroid Structure and Decreases T4 and T3 Serum Levels in Middle-Aged Female Rats
Authors: Šošić-Jurjević Branka , Filipović Branko , Milošević Verica , Nestorović Nataša , Manojlović-Stojanoski Milica , Brkić Branislava , Sekulić Milka
Published: January 2005

Objectives: In human medicine, estrogen is applied in prevention and treatment of health problems associated with the menopause. The aim of this study was to examine the effects of chronic estradiol dipropionate (EDP) treatment on thyroid gland structure and function in middle-aged female rats. Methods: At 14 months of age, Wistar rats received 0.625 mg EDP/kg b.w./day intraperitoneally for 2 weeks. The peripheral and central zones of the thyroid were stereologically analyzed and the following morphometric parameters determined: volume density of follicles, follicular epithelium, interstitium and colloid, epithelial height and the index of activation rate. Serum levels of TSH, T4 and T3 were determined by ELISA. Results: EDP treatment led to significant decreases in volume densities of follicles and follicular epithelium, epithelial height and index of activation rate (by 11%, p < 0.05; 23%, p < 0.005; 11%, p < 0.05 and 21%, p < 0.05, respectively) in comparison to control values. Hyperplasia of thyroid follicular cells was noticed in 25% of EDP-treated animals. Serum levels of T4 and T3 were decreased (by 33%, p < 0.005 and 28%, p < 0.001, respectively), but TSH concentration was not significantly different from that of the controls. Conclusion: Chronic estradiol treatment significantly decreased volume density and height of centrally located follicular epithelium, follicular activation index and serum level of total thyroid hormones in middle-aged rats.
Quality Assurance in Stereotactic Radiosurgery/Radiotherapy according to DIN 6875-1
Authors: Mack A. , Mack G. , Scheib S. , Czempiel H. , Kreiner H.J. , Lomax N.J. , Gianolini S. , Rieker M. , Weltz D. , Wolff R. , Muacevic A. , Wowra B. , Böttcher H.D. , Seifert V.
Published: January 2005

The new DIN (‘Deutsche Industrie-Norm’) 6875-1, which is currently being finalised, deals with quality assurance (QA) criteria and tests methods for linear accelerator and Gamma Knife stereotactic radiosurgery/radiotherapy including treatment planning, stereotactic frame and stereotactic imaging and a system test to check the whole chain of uncertainties. Our existing QA program, based on dedicated phantoms and test procedures, has been refined to fulfill the demands of this new DIN. The radiological and mechanical isocentre corresponded within 0.2 mm and the measured 50% isodose lines were in agreement with the calculated ones within less than 0.5 mm. The measured absorbed dose was within 3%. The resultant output factors measured for the 14-, 8- and 4-mm collimator helmet were 0.9870 ± 0.0086, 0.9578 ± 0.0057 and 0.8741 ± 0.0202, respectively. For 170 consecutive tests, the mean geometrical accuracy was 0.48 ± 0.23 mm. Besides QA phantoms and analysis software developed in-house, the use of commercially available tools facilitated the QA according to the DIN 6875-1 with which our results complied.
Tau Protein, Aβ42 and S-100B Protein in Cerebrospinal Fluid of Patients with Dementia with Lewy Bodies
Authors: Mollenhauer Brit , Cepek Lukas , Bibl Mirko , Wiltfang Jens , Schulz-Schaeffer Walter J. , Ciesielczyk Barbara , Neumann Manuela , Steinacker Petra , Kretzschmar Hans A. , Poser Sigrid , Trenkwalder Claudia , Otto Markus
Published: January 2005

The intra vitam diagnosis of dementia with Lewy bodies (DLB) is still based on clinical grounds. So far no technical investigations have been available to support this diagnosis. As for tau protein and β-amyloid(1–42) (Aβ42), promising results for the diagnosis of Alzheimer’s disease (AD) have been reported; we evaluated these markers and S-100B protein in cerebrospinal fluid (CSF), using a set of commercially available assays, of 71 patients with DLB, 67 patients with AD and 41 nondemented controls (NDC) for their differential diagnostic relevance. Patients with DLB showed significantly lower tau protein values compared to AD but with a high overlap of values. More prominent differences were observed in the comparison of DLB patients with all three clinical core features and AD patients. Aβ42 levels were decreased in the DLB and AD groups versus NDC, without significant subgroup differences. S-100B levels were not significantly different between the groups. Tau protein levels in CSF may contribute to the clinical distinction between DLB and AD, but the value of the markers is still limited especially due to mixed pathology. We conclude that more specific markers have to be established for the differentiation of these diseases.
Effects of Intravenous Polymaltose Iron on Oxidant Stress and Non-Transferrin-Bound Iron in Hemodialysis Patients
Authors: Driss Fathi , Vrtovsnik François , Katsahian Sandrine , Michel Catherine , Baron Gabriel , Kolta Amir , Sedrati Nadia , Mentré France , Mignon Françoise , Cabantchik Ioav , Grandchamp Bernard
Published: January 2005

Background: The use of intravenous iron to correct anemia in end-stage renal diseases (ESRD) has been suspected of catalyzing the production of activated oxygen species and promoting oxidative damage. We investigated the pro-oxidative potential of injected iron in hemodialysis patients. Methods: In study A, 65 patients with ESRD were studied. 20 patients received weekly infusions of iron polymaltose (maltofer), whereas 45 patients had been off iron therapy for more than 2 months. In study B, 12 patients were investigated during two consecutive hemodialysis sessions, one session without and one session with infusion of 100 mg of maltofer over 4 h. Serum iron status, non-transferrin-bound iron (NTBI) and markers of oxidative stress were studied in blood samples from these patients. Results: In study A, NTBI was detected in 41% of the patients and the proportion of NTBI-positive patients was the same whether or not they received iron therapy. In study B, the serum iron and transferrin saturation index increased during iron infusion and NTBI transiently appeared in some patients but markers of oxidative stress were not significantly affected. Conclusion: Although ESRD patients have a high prevalence of NTBI in their serum, no correlation could be established between the presence of NTBI and an increased oxidative stress. The slow infusion of maltofer does not promote a significant increase in the plasma concentration of oxidative stress markers. It may therefore be considered as a safe complement to erythropoietin therapy.
Plasma Concentrations of Brain Natriuretic Peptide in Patients with Acute Ischemic Stroke
Authors: Nakagawa Kazuhiko , Yamaguchi Takekane , Seida Mitsuru , Yamada Shimpei , Imae Shogo , Tanaka Yoji , Yamamoto Kiyotaka , Ohno Kikuo
Published: January 2005

Background: Acute blood pressure (BP) elevation and cardiac abnormalities are known to follow ischemic stroke. Brain natriuretic peptide (BNP), which is produced in response to such cardiovascular alterations, is expected to play a hemodynamic role. We measured plasma BNP concentrations in patients with cerebral infarction (CI) to determine the implications of BNP in acute ischemic stroke. Methods: Eighty-eight patients with CI, 59 with essential hypertension, 44 with spontaneous intracerebral hemorrhage, 22 with asymptomatic atrial fibrillation (Af), and 20 age- and sex-matched healthy volunteers were recruited in the study. CI patients were divided into 2 subgroups either having Af (27 patients) or not (61 patients). BNP levels were repeatedly measured in 58 patients with CI. BNP levels were compared between ischemic subgroups categorized by size of infarction. Correlation was investigated between BNP levels and hemodynamic parameters. Results: BNP levels in CI patients were significantly higher, but they decreased in the subacute period. BNP levels in CI patients without Af were correlated with mean arterial blood pressure (MAP) on admission or the degree of reduction in MAP at day 1, while in CI patients with Af BNP levels showed negative correlation with MAP on admission. Follow-up serum sodium levels in CI patients with Af were negatively correlated with BNP levels on admission. Conclusions: This study suggests the hemodynamic implications of BNP in acute ischemic patients.
Mortality and Cause of Death after Hospital Discharge in 10,981 Patients with Ischemic Stroke and Transient Ischemic Attack
Authors: Kimura Kazumi , Minematsu Kazuo , Kazui Seiji , Yamaguchi Takenori
Published: January 2005

Background: The aim of this study was to examine the 1-year cumulative mortality rate and cause of death, and to identify the predictive factors for death after hospital discharge following ischemic stroke and transient ischemic attack (TIA) using data from the Japan Multicenter Stroke Investigators’ Collaboration study. Methods: We prospectively registered 16,922 consecutive patients with acute ischemic stroke or TIA from May 1999 to April 2000 in 156 Japanese hospitals. We mailed a questionnaire to the 15,322 patients who were alive at hospital discharge. Results: 10,981 patients (6,945 men, 4,036 women, age 70 ± 11 years, median 71, range 19–100 years) were enrolled in the follow-up study. The mean follow-up period was 271 ± 110 days (median 272 days; range 1–487 days). The 1-year cumulative mortality was 6.8% (7.0% for 10,234 stroke patients and 3.5% for 747 TIA patients). The causes of death were: cerebrovascular disease, 24.1%; pneumonia, 22.6%; heart disease, 18.1%; cancer, 11.0%, and miscellaneous causes, 24.1%. Multivariate analysis suggested that male gender, age, diabetes mellitus, atrial fibrillation, history of stroke, nonlacunar stroke, functional disability and transfer to another hospital or nursing home on discharge were significant independent predictors of death during the follow-up period. Conclusions: The major causes of death after hospital discharge were found to be cerebrovascular diseases, pneumonia and heart diseases. Thus, in order to improve survival after hospital discharge, in addition to appropriate management of vascular risk factors following stroke, it appears to be important to take measures to prevent pneumonia and to discharge patients to their own home, if possible.
Botulinum Toxin: Mechanisms of Action
Authors: Dressler Dirk , Adib Saberi Fereshte
Published: January 2005

Botulinum toxin (BT) has been perceived as a lethal threat for many centuries. In the early 1980s, this perception completely changed when BT’s therapeutic potential suddenly became apparent. We wish to give an overview over BT’s mechanisms of action relevant for understanding its therapeutic use. BT’s molecular mode of action includes extracellular binding to glycoprotein structures on cholinergic nerve terminals and intracellular blockade of the acetylcholine secretion. BT affects the spinal stretch reflex by blockade of intrafusal muscle fibres with consecutive reduction of Ia/II afferent signals and muscle tone without affecting muscle strength (reflex inhibition). This mechanism allows for antidystonic effects not only caused by target muscle paresis. BT also blocks efferent autonomic fibres to smooth muscles and to exocrine glands. Direct central nervous system effects are not observed, since BT does not cross the blood-brain barrier and since it is inactivated during its retrograde axonal transport. Indirect central nervous system effects include reflex inhibition, normalisation of reciprocal inhibition, intracortical inhibition and somatosensory evoked potentials. Reduction of formalin-induced pain suggests direct analgesic BT effects possibly mediated by blockade of substance P, glutamate and calcitonin gene-related peptide.
The Major Grass Pollen Group 5 Allergen from Dactylis glomerata and Its C-Terminal Split Product Both Behave as Dimers: Implications for Allergen Standardization
Authors: van Oort Erica , Dieker Miranda C. , de Heer Pleuni G. , Peltre Gabriel , Aalberse Rob C. , van Ree Ronald
Published: January 2005

Background: On SDS-PAGE grass pollen group-5 allergens migrate as a doublet with an apparent molecular mass (Mr) of 25 kDa. Immunoblot analysis revealed additional group 5 reactivity at double and half this Mr. The aim of this study was to investigate these group 5 molecular entities and to compare their allergenicity and behavior in quantitative immunoassays. Methods: Group-5-specific monoclonal antibodies were produced and used for the development of a group-5-specific sandwich ELISA. Affinity-purified Dac g 5 was separated by SDS-PAGE/Western blotting; individual bands were analyzed by N-terminal sequencing. Size exclusion chromatography (SEC) in conjunction with group-5-specific ELISA, competitive RIA and RAST inhibition were used to analyze the size distribution of Dac g 5. Basophil histamine release assays were used to assess biological activity. Results: The lower band of the typical group 5 doublet was identified as a truncated form lacking the typical group 5 N-terminus ADL/AGY, observed in the upper band. The 12-kDa peptide was shown to be the C-terminal half of Dac g 5 (amino acid 127 onwards). SEC in conjunction with competitive RIA revealed that around 45% of Dac g 5 is represented by the 12-kDa peptide. Both the C-terminal half and the whole allergen dimerize under nondenaturing conditions. In competitive RIA and RAST inhibition both forms are equally well detected. In contrast, the half molecule is poorly recognized in sandwich ELISA and displays negligible biological activity in basophil histamine release tests with purified IgE. Conclusions: These observations stress the need to evaluate the performance of allergen standardization protocols in detail, with special attention to allergen size distribution.
Biochemical and Immunological Characterization of Pollen-Derived β-Galactosidase Reveals a New Cross-Reactive Class of Allergens among Mediterranean Trees
Authors: Bistoni Onelia , Emiliani Carla , Agea Elisabetta , Russano Anna M. , Mencarelli Simona , Orlacchio Aldo , Spinozzi Fabrizio
Published: January 2005

Background: The most potent allergens in the Spermatophytae family exhibit significant homology with enzymes. Some of these are though to be involved in pectin metabolism, recognition of compatible stigma and delivery of sperm cells to the ovule. Objective: To test if glycohydrolase activities from some Mediterranean tree pollens could act as allergens in sensitized hosts. Methods: Freshly collected Cupressus and Olea pollens were investigated for their glycohydrolase activities by means of synthetic fluorogenic substrates and isoenzymes characterized by DEAE-cellulose ion-exchange chromatography. Binding of specific IgE was investigated by immunoblotting in 30 tree-sensitive subjects, as well as in 20 atopic non-tree-sensitive and 15 healthy controls. The enzymes were also adopted to stimulate proliferation of allergen-specific T cell clones. Finally, they were tested in vivo in a cutaneous immediate wheal and flare reaction. Results: β-Galactosidase (β-GAL) is present with different isoenzymatic patterns on both pollen extracts, could be recognized by circulating IgE, as well as immunoprecipitated by sera from allergic subjects. The enzyme could stimulate the proliferation of T cells from allergic subjects, and favor the emergence of CD4+ T cell clones with specific in vitro reactivity to β-GAL. Finally, the enzyme induced in vivo a cutaneous wheal and flare reaction in clinically sensitive subjects. Conclusions: Despite different isoenzymatic patterns, Olea-derived β-GAL cross-reacted with that from cypress pollen, suggesting that these enzymatic glycoproteins may represent major native allergens among these Mediterranean trees.
Pranlukast, a Leukotriene Receptor Antagonist, Inhibits Interleukin-5 Production via a Mechanism Distinct from Leukotriene Receptor Antagonism
Authors: Fukushima Chizu , Matsuse Hiroto , Hishikawa Yoshitaka , Kondo Yuki , Machida Ikuko , Saeki Sachiko , Kawano Tetsuya , Tomari Shinya , Obase Yasushi , Shimoda Terufumi , Koji Takehiko , Kohno Shigeru
Published: January 2005

Background: Pranlukast, a cysteinyl leukotriene receptor 1 (CysLTR1) antagonist, inhibits not only airway smooth muscle contraction, but also allergic inflammation. The aim of this study was to determine the mechanism of pranlukast-induced interleukin-5 (IL-5) inhibition in allergic inflammation. Methods: Surgically resected human lung tissue was passively sensitized in vitro with mite-allergen-sensitized sera, followed by stimulation with mite allergen after pretreatment of the tissue with pranlukast, dexamethasone, or both. The IL-5 protein level in the culture medium was measured, and in situ hybridization of IL-5 and CysLTR1 mRNA was performed using lung tissues. Results: Pretreatment of lung tissues with pranlukast alone significantly decreased the amount of IL-5 protein in the culture medium by 40%. The combination of pranlukast and dexamethasone synergistically enhanced this effect. Quantitative in situ hybridization with image analysis revealed abundant expression of IL-5 mRNA in eosinophils, lymphocytes, and mast cells in sensitized and allergen-stimulated lung tissues. CysLTR1 mRNA was detected in macrophages, smooth muscle cells, eosinophils, and mast cells, but was less expressed in lymphocytes. Pranlukast-induced inhibition of IL-5 mRNA expression was noted in various cells, irrespective of their CysLTR1 mRNA expression status. In addition, cysteinyl leukotrienes per se failed to upregulate the IL-5 production. Conclusion: Our results indicate that pranlukast inhibits IL-5 synthesis via a mechanism distinct from CysLTR1 antagonism.
Distortion Product Otoacoustic Emissions after Intratympanic Gentamicin Therapy for Unilateral Ménière’s Disease
Authors: Perez Nicolas , Boleas M , Martin Eduardo
Published: January 2005

The treatment of patients with Ménière’s disease that do not respond to conventional therapy becomes complicated, particularly when taking into account the issue of hearing damage as well as the control of vertigo. Treatment often involves the intratympanic administration of gentamicin, for which different protocols are used. Hence, it is important that we better understand how this treatment influences hearing, beyond mere audiometric assessments. The aim of this prospective study was to evaluate the effect of intratympanic gentamicin treatment for Ménière’s disease on cochlear function, as assessed by otoacoustic emissions. The 41 patients included in the study had been diagnosed with unilateral Ménière’s disease as defined by the American Academy of Otolaryngology-Head and Neck Surgery guidelines (1995), and had been refractory to medical treatment for at least 1 year. Intratympanic injections of gentamicin at a concentration of 27 mg/ml were performed at weekly intervals until indications of vestibular hypofunction appeared in the treated ear. Before beginning the treatment and 3 months after ending it, pure tone and speech audiometry tests were performed and the results are expressed in terms of the pure tone average (0.5, 1, 2, and 3 kHz) and the speech discrimination score, respectively. At the same time, a distortion product otoacoustic emission (DPOAE) study was performed and the results are expressed in terms of its presence or absence, and as the amplitude and threshold of the emission. When analyzed 3 months after the treatment had terminated, hearing loss was seen in 13 patients (31.7%). However, no significant change in the threshold and/or amplitude of otoacoustic emissions was observed in any of the patients. Neither were changes in the audiometric stage, number of injections required or the existence of DPOAE before treatment detected. Hence, the treatment method used here for patients with intractable unilateral Ménière’s disease can be considered as having a low risk on auditory function, as assessed both audiometrically and with otoacoustic emissions, and can be considered as subablative for hearing function.
Serial Audiometry and Speech Recognition Findings in Finnish Usher Syndrome Type III Patients
Authors: Plantinga R.F. , Kleemola L. , Huygen P.L.M. , Joensuu T. , Sankila E.-M. , Pennings R.J.E. , Cremers C.W.R.J.
Published: January 2005

Audiometric features, evaluated by serial pure tone audiometry and speech recognition tests (n = 31), were analysed in 59 Finnish Usher syndrome type III patients (USH3) with Finmajor/Finmajor (n = 55) and Finmajor/Finminor (n = 4) USH3A mutations. These patients showed a highly variable type and degree of progressive sensorineural hearing impairment: from normal to moderate USH2A-like hearing impairment at young ages to profound or even USH1B-like hearing impairment at more advanced ages. Compound heterozygous patients generally showed a milder phenotype. The highest progression was seen during the first two decades of life, gradually slowing down with further ageing. This type of non-linear progression may be unique amongst the Usher syndromes. Speech recognition started to deteriorate at highly variable ages. In some patients, it jeopardised normal speech and language development, whereas in others it was still remarkably good at advanced ages.
Aging Effects on Vestibulo-Ocular Responses in C57BL/6 Mice: Comparison with Alteration in Auditory Function
Authors: Shiga Atsushi , Nakagawa Takayuki , Nakayama Meiho , Endo Tsuyoshi , Iguchi Fukuichiro , Kim Tae-Soo , Naito Yasushi , Ito Juichi
Published: January 2005

Age-related changes in auditory function are well documented in animal models; however, this is not the case as regards vestibular function. In this study, we evaluated age-related changes in vestibulo-ocular responses in C57BL/6 mice that are considered as a model of presbycusis. The functional data were substantiated by the findings of histological analysis of vestibular and auditory peripherals. The gain in vestibulo-ocular reflex, which reflects functionality of the vestibular system, increased in an age-dependent manner until 12 weeks and exhibited limited functional loss due to aging after 24 weeks. By contrast, no alteration in the thresholds of the auditory brainstem response (ABR) was observed from 3 to 12 weeks of age; however, ABR thresholds were significantly elevated from age 24 weeks and onwards. Histological analysis demonstrated that the degeneration of auditory peripherals was closely related with functional loss due to aging. Vestibular peripherals also exhibited age-related degeneration morphologically, although age-related dysfunction was not apparent. Age-related changes in the vestibular function of C57BL/6 mice followed a different time course when compared to changes in auditory function. These findings indicate that mechanisms for age-related changes in vestibular function differ from those of auditory function.
Normative Findings of Electrically Evoked Compound Action Potential Measurements Using the Neural Response Telemetry of the Nucleus CI24M Cochlear Implant System
Authors: Cafarelli Dees D. , Dillier N. , Lai W.K. , von Wallenberg E. , van Dijk B. , Akdas F. , Aksit M. , Batman C. , Beynon A. , Burdo S. , Chanal J.-M. , Collet L. , Conway M. , Coudert C. , Craddock L. , Cullington H. , Deggouj N. , Fraysse B. , Grabel S. , Kiefer J. , Kiss J.G. , Lenarz T. , Mair A. , Maune S. , Müller-Deile J. , Piron J.-P. , Razza S. , Tasche C. , Thai-Van H. , Toth F. , Truy E. , Uziel A. , Smoorenburg G.F.
Published: January 2005

One hundred and forty-seven adult recipients of the Nucleus® 24 cochlear implant system, from 13 different European countries, were tested using neural response telemetry to measure the electrically evoked compound action potential (ECAP), according to a standardised postoperative measurement procedure. Recordings were obtained in 96% of these subjects with this standardised procedure. The group results are presented in terms of peak amplitude and latency, slope of the amplitude growth function and ECAP threshold. The effects of aetiological factors and the duration of deafness on the ECAP were also studied. While large intersubject variability and intrasubject variability (across electrodes) were found, results fell within a consistent pattern and a normative range of peak amplitudes and latencies was established. The aetiological factors had little effect on the ECAP characteristics. However, age affected ECAP amplitude and slope of the amplitude growth function significantly; i.e., the amplitude is higher in the lowest age category (15–30 years). Principal component analysis of the ECAP thresholds shows that the thresholds across 5 electrodes can be described by two factors accounting for 92% of the total variance. The two factors represent the overall level of the threshold profiles (‘shift’) and their slopes across the electrode array (‘tilt’). Correlation between these two factors and the same factors describing the T- and C-levels appeared to be moderate, in the range of 0.5–0.6.
Mechanism of Contraction of Rat Isolated Tail Arteries by Hyposmotic Solutions
Authors: Wijetunge S. , Hughes A.D.
Published: January 2005

Contraction induced by hyposmotic swelling was examined in rat tail arteries mounted on a myograph containing a modified Krebs physiological saline solution (PSS) containing 50 mM mannitol (300 mosm/l). Hyposmotic swelling was induced by removing mannitol. In arteries having basal tone or arteries precontracted with K+ or the thromboxane mimetic U-46619, removal of mannitol caused a concentration dependent contraction of rat tail arteries. Concurrent measurement of tension and intracellular calcium [Ca2+]i in arteries loaded with fura-2 showed that both tension and [Ca2+]i increased on exposure to a hyposmotic solution. Removal of endothelium or inhibition of nitric oxide and cyclooxygenase together did not affect contractile responses. Removal of extracellular Ca2+ abolished the contractile response to hyposmotic solution and NiCl2, a nonspecific inhibitor of Ca2+ influx pathways, blocked the rise in [Ca2+]i and tension in response to a hyposmotic solution. Verapamil and nisoldipine, inhibitors of Cav1.2 (L-type) calcium channels significantly reduced the contractile response to a hyposmotic solution. Addition of NiCl2 to nisoldipine caused an additional inhibition of the response to a hyposmotic solution. Inhibition of calcium release from the sarcoplasmic reticulum by ryanodine or cyclopiazonic acid (CPA) did not cause any change in the tension response to a hyposmotic solution. CPA did not significantly inhibit the response to a hyposmotic solution in the presence of NG-methyl-L-arginine, oxyhaemoglobin and indomethacin. We conclude that contraction induced by a hyposmotic solution is largely due to Cav1.2 calcium channels although other Ca2+ influx pathways also contribute.
Clinical Relevance of Differences between Various Beta-Blockers
Authors: Vintila Marius Marcian
Published: January 2005

More than 15 beta-blockers are available today. They represent a class I recommendation in major cardiovascular disorders such as hypertension, coronary heart disease and chronic heart failure. If in hypertension and coronary heart disease their favorable action is considered a class effect, in heart failure some of them are of more benefit than others. Bisoprolol, carvedilol and metoprolol proved in important clinical trials significant reductions in mortality and morbidity in patients with different stages of heart failure, from asymptomatic ventricular dysfunction to NYHA class IV heart failure. The newcomer nebivolol reduced morbi-mortality in old and very old patients as shown in the recently presented SENIORS study.
Clinical Efficacy of Ivabradine
Authors: Tardif Jean-Claude
Published: January 2005

Ivabradine is the first selective and specific If inhibitor with a complete clinical development program. This new pharmacological class represents a novel approach to heart rate reduction that could be of special relevance in different clinical situations such as stable angina. Ivabradine was shown to reduce resting heart rate without modifying any major electrophysiological parameters. Thus, exclusive heart rate reduction can be achieved in the clinic as a result of specific and selective If current inhibition. Ivabradine efficacy has been evaluated in a large clinical program in stable angina. This article will present the results of four randomized clinical studies which have evaluated the efficacy of ivabradine in stable angina patients. Ivabradine was shown to be superior to placebo in improving exercise tolerance test (ETT) criteria (n = 360). In a 4-month, double-blind, controlled study (n = 939), ivabradine 5 and 7.5 mg twice daily was shown to be at least as effective as atenolol 50 and 100 mg once daily. Furthermore, the anti-ischemic and antianginal efficacy of ivabradine has been demonstrated versus amlodipine (n = 1,195), improving total exercise duration and other ETT criteria, and reducing the frequency of angina attacks. Additionally, ivabradine maintains its antianginal efficacy in the long term. Ivabradine therefore represents a valuable treatment for patients with stable angina.
The Era of Statins – Is There Still a Place for Other Classes of Lipid-Lowering Drugs?
Authors: Wascher Thomas C.
Published: January 2005

Plenty of evidence suggests statins as the first-line therapy for the treatment of lipid disorders. However, further therapeutic options available in the treatment of lipid disorders are fibrates, niacin and cholesterol absorption inhibitors. In the present study, current treatment modalities of lipid disorders are reviewed, and their use was scrutinized based on the available evidence.
Potassium Must Be Considered in Congenital Long QT Syndrome
Authors: Christiansen Michael , Kjeldsen Keld , Wettrell Göran , Larsen Lars A. , Lundkvist Lennart , Andersen Paal S. , Tran Cao T. , Kanters Jørgen K. , Vuust Jens
Published: January 2005

Background: Congenital long QT syndrome (cLQTS), characterized by prolonged QTc time, syncope or sudden death caused by torsade de pointes ventricular tachycardia, has an autosomal dominant pattern of inheritance and is caused by mutations in genes coding for the cardiac ion channels conducting the depolarizing sodium current, INa, and the repolarizing delayed rectifier potassium currents, IKr and IKs. Methods: We describe a family in which one family member died suddenly and unexpectedly from what was assumed to be cardiac death, and in which another person with symptoms indicating cLQTS had been controlled for more than 40 years with oral potassium chloride and ammonium chloride. She was screened for mutations in LQTS genes using polymerase chain amplification reaction of genomic DNA followed by single-strand conformation polymorphism analysis. Results: A clinically well-described missense mutation, G306R in KCNQ1, coding for the ion channel conducting the IKs current was found. The mutation causes a moderately dominant reduction in the IKs current. Conclusion: The novel observation is that potassium in cLQTS caused by the KCNQ1 mutation protects against syncope in a life-long perspective. Thus, although the mechanism is not fully elucidated, maintaining a normal potassium homeostasis is of general importance. Hence, securing sufficient intake of potassium and careful control of potassium-losing conditions are important elements in the management of patients with cLQTS as a supplement to established therapeutic strategies.
Comparative Study on the Effects of Cyclosporin A in Renal Cells in Culture
Authors: Nascimento Clarissa R. , Braga Filipe , Capella Luiz S. , Santos Omar R. , Lopes Aníbal G. , Capella Marcia A.M.
Published: January 2005

Background: Although cyclosporin A (CSA) inhibits P-glycoprotein (ABCB1), the relationship between this inhibition and CSA-induced nephrotoxicity is not established. Methods: Three renal cell lines were used to investigate the effects of CSA in cellular viability and accumulation of rhodamine 123 (Rho123): LLC-PK1, which does not express ABCB1 substantially; MDCK, expressing moderate amounts of this protein, and Ma104 cells, which express high amounts of ABCB1. Results: The viability was significantly reduced in the three cell lines after treatment with CSA concentrations >10 µM. Ma104 was the more resistant and LLC-PK1 the more sensitive. CSA increased Rho123 accumulation in the three cell lines when incubated simultaneously, MDCK presenting the higher increase. However, different results were achieved when the periods of incubation with Rho123 and CSA were disconnected: a post-incubation with CSA was more effective in Ma104 cells, while MDCK and LLC-PK1 showed no difference between pre-, co- and post-incubation with CSA. Conclusions: Our results suggest that the effects of CSA may be divided into two groups: ABCB1-independent (direct injury), and ABCB1-dependent toxicity, due to modulation of its activity. This could result in increased accumulation of noxious ABCB1 substrates, contributing to CSA-induced nephrotoxicity. Furthermore, the mechanisms of ABCB1 modulation by CSA may be different for different cell lines.
Serum Cross-Linked N-Terminal Telopeptide of Type I Collagen for Evaluation of Renal Osteodystrophy in Hemodialysis Patients
Authors: Nakashima Ayumu , Yorioka Noriaki , Mizutani Takashi , Yamagata Zentaro , Ueno Toshinori , Takasugi Norihisa
Published: January 2005

Background: Useful markers of bone resorption are needed for hemodialysis patients with renal osteodystrophy. This study investigated the use of a new immunoassay for cross-linked N-terminal telopeptide of type 1 collagen to assess bone changes in hemodialysis patients. Methods: Radial bone mineral density was examined in 178 hemodialysis patients at baseline and after 12 months. Serum levels of N-terminal telopeptide and other markers were measured. Results: The annual percent change of radial bone mineral density was negatively correlated with the levels of N-terminal telopeptide, intact osteocalcin, tartrate-resistant acid phosphatase, bone-specific alkaline phosphatase, and intact parathyroid hormone. The annual percent change of radial bone mineral density showed a stronger correlation with N-terminal telopeptide levels than with the other markers, except for intact parathyroid hormone. Also, intact parathyroid hormone and N-terminal telopeptide levels showed a stronger correlation than that of either tartrate-resistant acid phosphatase or cross-linked carboxyterminal telopeptide of type 1 collagen with intact parathyroid hormone. Conclusion: Serum N-terminal telopeptide may be the most useful bone resorption marker in renal osteodystrophy and its use combined with bone formation markers may improve the management of this condition.
Blood Pressure Control before and after Starting Dialysis
Authors: Dasgupta Indranil , Burden Richard
Published: January 2005

Background/Aim: We have previously reported a study on the adequacy of management of hypertension in patients developing end-stage renal failure (ESRF) over a period of 3 years from a single health district in the UK (n = 107). There were significant shortcomings in all aspects of management of hypertension including blood pressure (BP) control. Methods: In this report, we have compared BP control in the same cohort of patients before and after starting renal replacement therapy (RRT). Results: BP control improved significantly after the patients were established on dialysis (mean 158/ 87 mm Hg pre-RRT vs. 152/82 mm Hg post-RRT; p < 0.0001), and fewer antihypertensive agents were prescribed to control BP (mean 2.45 vs. 1.74) in this period (p < 0.0001). Moreover, patients on continuous ambulatory peritoneal dialysis (n = 50) had a better systolic BP control compared with the haemodialysis patients (n = 57; p = 0.03). Conclusions: This study shows significant improvement in BP control in a cohort of patients with ESRF following the start of dialysis.