bluuebunny/crossref_metadata_2025 huggingface dataset:
Epitope scanning reveals gain and loss of strain specific antibody binding epitopes associated with the conversion of normal cellular prion to scrapie prion
Authors: Pan Tao , Li Ruliang , Kang Shin‐Cheng , Wong Boon‐Seng , Wisniewski Thomas , Sy Man‐Sun
Published: August 2004

We used anti‐prion (PrP) monoclonal antibodies (Mabs) in different combinations to scan changes in the availability of antibody binding epitopes – using an epitope scanning assay – in brain homogenates from normal mice, and from mice infected with either ME7 or 139 A strains of infectious scrapie prion (PrPSc). In ME7‐infected brains, the epitope detected by the Mab pair 8B4/8H4 is reduced, while the epitope detected by the Mab pair 8F9/11G5 is increased. Mab 8F9/11G5 detect a conformational epitope on PrPScbecause the rise in Mab 8F9/11G5 binding is sensitive to a denaturing agent but resistant to proteinase K (PK). While the increase in Mab 8F9/11G5 binding correlates with the presence of PK‐resistant PrP and clinical signs of infection, the reduction in Mab 8B4/8H4 binding is detected earlier. Fractionation of the ME7‐infected brain homogenate in sucrose gradient revealed that the PrPScspecies detected by the epitope scanning assay are heterogeneous in size, with a molecular mass of ≈ ≥ 2000‐kDa. We also investigated whether these findings were applicable to two other strains of PrPSc, namely 87 V and 22 L. We found that the decrease in Mab 8B4/8H4 binding detected in ME7‐infected brains was also detected in 87 V‐infected brains but not in 22 L‐infected brains. In contrast, the increase in Mab 8F9/11G5 binding detected in ME7‐ and 139 A‐infected brains was also detected in 22 L‐infected brains but not in 87 V‐infected brains. Therefore, each prion strain has its unique conformation, and we can monitor the conversion of normal cellular prion (PrPC) to PrPScbased on the changes in the antibody binding patterns. The epitope can be decreased or increased, linear or conformational, detected late or early during infection, in a strain specific manner.
Excitatory amino acid induced oligodendrocyte cell death in vitro: receptor‐dependent and ‐independent mechanisms
Authors: Rosin Claudia , Bates Timothy E. , Skaper Stephen D.
Published: August 2004

Oligodendroglia play an important role in axonal conduction in the CNS and are sensitive to oxidative toxicity induced by glutamate in the absence of ionotropic glutamate receptors. In this study, oligodendrocyte signalling cascades were examined, in response to glutamate‐induced oxidative injury and to excitotoxicity. Rat cortical oligodendrocytes, differentiated in culture, were highly vulnerable to glutamate‐induced cell death. Competitive inhibition of cystine uptake and increased oxidative stress appeared responsible for this death, and caused an accumulation of intracellular peroxides as well as chromatin fragmentation and condensation. Glutamate receptor subtype agonists (quisqualate, ibotenate) known to inhibit cystine uptake were cytotoxic, but not NMDA itself; moreover, glutamate receptor antagonists were not protective. Oligodendrocytes were also vulnerable to overactivation of glutamate receptors, as kainic acid and AMPA proved to be toxic. AMPA toxicity required the presence of cyclothiazide, suggesting rapid desensitization of AMPA receptors. Glutamate‐induced oxidative stress and kainate/AMPA receptor stimulation activated the mitogen‐activated protein kinase (MAP kinase) pathway, as well as the transcription factor ELK. However, MAP kinase kinase inhibitors only protected against injury from glutamate‐induced oxidative stress. Oligodendrocytes were sensitive to oxygen–glucose deprivation injury as well, in a MAP kinase dependent fashion. Glutamate toxicity may conceivably be operative in neuropathological conditions that disrupt neuronal/oligodendrocyte interactions in axons, e.g. multiple sclerosis and ischaemia‐reperfusion injury.
DASB –in vitro binding characteristics on human recombinant monoamine transporters with regard to its potential as positron emission tomography (PET) tracer
Authors: Hummerich René , Reischl Gerald , Ehrlichmann Walter , Machulla Hans‐Jürgen , Heinz Andreas , Schloss Patrick
Published: August 2004

The efficiency of serotonergic signal transduction is controlled by the density of serotonegic synapses and by the activity of the serotonin transporter (SERT), which selectively clears the synaptic cleft of the neurotransmitter. SERT is located in axons, where it is concentrated in varicosities and terminal boutons and thus is an exquisite marker for serotonergic synapses. This finding has been taken advantage of for neuroimaging serotonergic synaptic contact sites. Previous positron emission tomography (PET) and single photon emission computed tomography (SPECT) studies were often carried out using radioligands that bind with high affinity to SERTs in the brainstem but also exhibit high affinity for dopamine and norepinephrine transporters and therefore did not allow quantification of serotonergic innervations in brain regions also containing dopaminergic or noradrenergic terminals. In order to visualize SERT availability more selectively, in recent years new tracers have been developed, one of which is [11C]DASB (N,N‐dimethyl‐2‐2‐amino‐4‐cyanophenylthiobenzylamine). Here, we have performed a detailed pharmacological characterization of unlabelled as well as radioactive DASB on recombinant human monoamine transporter proteins. Our results show that DASB selectively binds to SERT with high affinity (KD = 3.5 nm) to a site distinct from the serotonin (5‐HT) recognition/translocation site. 5‐HT inhibits DASB binding to SERT with more than one order of magnitude lower affinity than that of DASB binding (IC50 = 82.4 nm). These findings suggest DASB to be a highly selective PET tracer to visualize the density of serotonergic synapses in human brain.
The C‐terminal domain of the heavy chain of tetanus toxin rescues cerebellar granule neurones from apoptotic death: involvement of phosphatidylinositol 3‐kinase and mitogen‐activated protein kinase pathways
Authors: Chaïb‐Oukadour Imane , Gil Carles , Aguilera José
Published: August 2004

When cultured cerebellar granule neurones are transferred from a medium containing high extracellular potassium concentration ([K+]e) (25 mm) to one with lower [K+]e (5 mm), caspase‐3 activity is induced and cells die apoptotically. In contrast, if cells in non‐depolarizing conditions are treated with brain‐derived neurotrophic factor (BDNF), caspase‐3 activity, chromatin condensation and cell death are markedly diminished. In this study, we show that the C‐terminal domain of the tetanus toxin heavy‐chain (Hc‐TeTx) is able to produce the same neuroprotective effect, as assessed by reduction of tetrazolium salts and by chromatin condensation. Hc‐TeTx‐conferred neuroprotection appears to depend on phosphatidylinositol 3‐kinase (PI3K) and mitogen‐activated protein kinase kinase, as is demonstrated by the selective inhibitors Wortmannin and PD98059, respectively. Hc‐TeTx also induces phosphorylation of the tyrosine kinase BDNF receptor, activation of p21Ras in its GTP‐bound form, and phosphorylation of the cascade including extracellular‐signal‐regulated kinases‐1/2 (ERK‐1/2), p90 ribosomal S6 kinase (p90rsk) and CREB (cAMP‐response‐element‐binding protein). On the other hand, activation of the Akt pathway is also detected, as well as inhibition of the active form of caspase‐3. These results point to an implication of both PI3K‐ and ERK‐dependent pathways in the promotion of cerebellar granule cell survival by Hc‐TeTx.
Zinc inhibits glutamate release via activation of pre‐synaptic KATP channels and reduces ischaemic damage in rat hippocampus
Authors: Bancila Victor , Nikonenko Irina , Dunant Yves , Bloc Alain
Published: August 2004

Zinc is concentrated in certain CNS excitatory tracts, especially in hippocampal mossy fibres where it has been suggested to modulate synaptic transmission and plasticity. Using rat mossy fibre synaptosomes depolarized by 4‐aminopyridine, we show here that low zinc concentrations restore the membrane potential and reduce glutamate release. Both effects arose from activation of ATP‐sensitive potassium channels (KATP), since they were mimicked by the KATP opener diazoxide and antagonized by the KATP blocker tolbutamide. Using recombinant channels expressed in COS‐7 cells, we confirmed that micromolar zinc did activate KATP of the type found in hippocampus. We tested the hypothesis that this action of zinc could be beneficial during an ischaemic challenge by using organotypic hippocampal slice cultures. When zinc was applied at micromolar concentrations during a brief anoxic‐hypoglycaemic episode, it significantly attenuated the ensuing neuronal death, whereas chelation of endogenous zinc markedly aggravated cell damage. Protective effect of zinc was mediated through KATP, as was shown by using the opener diazoxide and the blocker tolbutamide. Thus, by activating pre‐synaptic KATP channels, zinc protects neurones from hyper‐excitation, excessive transmitter release and exitotoxicity, and may thus act as an endogenous neuroprotector in conditions such as epilepsy or stroke.
Activity of protein phosphatase calcineurin is decreased in sporadic and familial amyotrophic lateral sclerosispatients
Authors: Ferri Alberto , Nencini Monica , Battistini Stefania , Giannini Fabio , Siciliano Gabriele , Casali Carlo , Damiano Maria G. , Ceroni Mauro , Chiò Adriano , Rotilio Giuseppe , Carrì Maria Teresa
Published: August 2004

Calcineurin (CaN) is a Ser/Thr protein phosphatase involved in a wide range of cellular responses to calcium mobilizing signals. Previous evidence supports the notion that calcineurin is oxidatively inhibited by mutant Cu, Zn superoxide dismutase (SOD1) typical of familial ALS patients in vitro and in transgenic mice. We report that calcineurin activity is markedly inhibited in lymphocytes from 37 sporadic, eight familial ALS patients and an asymptomatic subject carrying an SOD1 mutation as compared to 28 healthy controls. Two other healthy subjects, heterozygous for the D90A mutation from a recessive pedigree, have normal calcineurin activity. Immunoreactive CaN protein, age, sex and riluzole treatment are not related to calcineurin activity in samples from patients. However, we have observed a marked increase in total protein oxidation in extracts from ALS lymphocytes, as compared to extracts from control subjects. These data confirm that modification of calcineurin activity and possibly of calcineurin‐mediated pathways of signal transduction (including modulation of apoptotic neuronal death) may contribute to the pathogenesis of ALS.
Stress increases dynorphin immunoreactivity in limbic brain regions and dynorphin antagonism produces antidepressant‐like effects
Authors: Shirayama Yukihiko , Ishida Hisahito , Iwata Masaaki , Hazama Gen‐i , Kawahara Ryuzou , Duman Ronald S.
Published: August 2004

Rats exposed to learned helplessness (LH), an animal model of depression, showed a recovery following an intracerebroventricular injection of nor‐binaltorphimine dihydrochloride (norBNI; a κ‐opioid antagonist). To investigate the potential role of dynorphin A and dynorphin B, we examined the effects of different stress/depression models on dynorphin A and dynorphin B immunoreactivity in hippocampus and nucleus accumbens (NAc). Immobilization stress (3 h) caused an increase in levels of dynorphin A and dynorphin B immunoreactivity in the hippocampus and the NAc. Forced swim stress also temporally increased dynorphin A levels in the hippocampus. Furthermore, exposure to LH produced a similar increase in dynorphin A and dynorphin B in the hippocampus and NAc. Infusions of norBNI into the dentate gyrus or CA3 regions of hippocampus and into the shell or core regions of NAc produced antidepressant‐like effects in the LH paradigm. The degrees of norBNI's effects were stronger in the CA3 region and NAc shell and less effective in the dentate gyrus of hippocampus and NAc core. These results indicate that both dynorphin A and dynorphin B contribute to the effects of stress, and suggest that blockade of κ‐opioid receptors may have therapeutic potential for the treatment of depression.
Progressive elevations in AMPA and GABAA receptor levels in deafferented somatosensory cortex
Authors: He Hai‐yan , Rasmusson Douglas D. , Quinlan Elizabeth M.
Published: August 2004

Restricted receptive fields (RFs), a hallmark of mature sensory systems, are actively maintained by a balance between ascending excitation and local inhibition in the cortex. Deafferentation disrupts this balance, allowing a sequence of changes in neuronal response properties that culminate in the reorganization of cortical RFs. To explore the molecular basis of deafferentation‐induced RF reorganization, we tracked changes in AMPA receptor (AMPAR), NMDA receptor (NMDAR) and GABAA receptor (GABAAR) levels in the deafferented somatosensory cortex of adult raccoons following single‐digit amputation. In synaptoneurosomes prepared from deafferented cortex, we observe a significant increase in AMPARs, but no change in NMDARs, 1–9 days post‐deafferentation, coincident with the appearance of new excitatory inputs and enlarged RFs. We observe a significant increase in GABAARs 2–7 weeks post‐deafferentation, coincident with a return of inhibitory input and shrinking RFs. These experience‐dependent changes in the levels of the major cortical ionotropic receptors were transient, returning to pre‐experimental baseline by ≥ 17 weeks post‐deafferentation, when RFs return to original size, but are remapped to different loci. This suggests that deafferentation‐induced cortical reorganization may be generated by activity‐dependent potentiation of weak excitatory synapses, followed by an increase in the strength of inhibitory synapses, resulting in finely tuned, remapped cortical RFs.
Metabolism of angiotensin II is required for its in vivo effect on dopamine release in the striatum of the rat
Authors: Stragier Bart , Sarre Sophie , Vanderheyden Patrick , Vauquelin Georges , Fournié‐Zaluski Marie‐Claude , Ebinger Guy , Michotte Yvette
Published: August 2004

The effect of angiotensin (Ang) IV, an inhibitor of insulin‐regulated aminopeptidase (IRAP), on extracellular dopamine levels in the striatum of freely moving rats was examined using in vivo microdialysis. The Ang IV was administered locally in the striatum through the microdialysis probe. A concentration‐dependent (10–100 µm) increase in extracellular striatal dopamine was observed. The effect of Ang II (10–100 µm), which has only a weak affinity for IRAP, was similar to that observed for Ang IV. The effects of both peptides could not be blocked by the AT1 antagonist candesartan (10 nm and 1 µm) nor by the AT2 antagonist S‐(+)‐1‐([4‐(dimethylamino)‐3‐methylphenyl]methyl)‐5‐(diphenyl‐acetyl)‐4,5,6,7‐tetrahydro‐1H‐amidazo(4,5‐c) pyridine‐6‐carboxylic acid (1 µm), suggesting that the observed effects are both AT1 and AT2 independent. The effect of Ang II could be blocked by the aminopeptidase‐A inhibitor (S)‐3‐amino‐4‐mercaptobutylsulphonic acid as well as the aminopeptidase‐N inhibitor 2‐amino‐4‐methylsulphonylbutane thiol, indicating that the effect of Ang II is mediated via metabolism into Ang IV. Other IRAP inhibitors, such as Divalinal‐Ang IV and LVV‐haemorphin‐7, had similar effects on extracellular dopamine levels as compared with Ang IV. We propose a role for IRAP as mediator for the effects of Ang IV and related peptides on extracellular dopamine levels in the striatum of the rat.
Permissive role of adenosine A2A receptors on metabotropic glutamate receptor 5 (mGluR5)‐mediated effects in the striatum
Authors: Domenici M. R. , Pepponi R. , Martire A. , Tebano M. T. , Potenza R. L. , Popoli P.
Published: August 2004

The metabotropic glutamate receptors 5 (mGlu5Rs) and the adenosine A2A receptors (A2ARs) have been reported to functionally interact in the striatum. The aim of the present work was to verify the hypothesis that the state of activation of A2A Rs could influence mGlu5R‐mediated effects in the striatum. In electrophysiological experiments (extracellular recording in rat corticostriatal slices), the ability of the selective mGlu5R agonist CHPG to potentiate the reduction of the field potential amplitude induced by NMDA was prevented not only by the selective mGlu5R antagonist MPEP, but also by the selective A2AR antagonist ZM 241385. Analogously, the application of CHPG potentiated NMDA‐induced toxicity (measured by LDH release) in cultured striatal neurons, an effect that was abolished by both MPEP and ZM 241385. Finally, the A2AR agonist CGS 21680 potentiated CHGP effects, an action that was reproduced and abolished, respectively, by forskolin (an activator of the cAMP/protein kinase A, PKA, pathway) and KT 5720 (a PKA inhibitor). The results indicate that A2ARs exert a permissive role on mGlu5R‐induced effects in the striatum. Such an interaction may represent an additional target for the development of therapeutic strategies towards striatal disorders.
Effect of valproic acid on serotonin‐2A receptor signaling in C6 glioma cells
Authors: Sullivan N. R. , Burke T. , Siafaka‐Kapadai A. , Javors M. , Hensler J. G.
Published: August 2004

Valproic acid (VPA), which has demonstrated efficacy in the treatment of bipolar disorder, has been shown to alter components of the phosphoinositide (PI) signaling cascade and to increase gene expression mediated by the transcription factor activator protein 1 (AP‐1). Central serotonin‐2A (5‐HT2A) receptors, which have been implicated in the pathophysiology of manic‐depressive illness, are coupled to PI hydrolysis. The promoter region of the 5‐HT2A receptor gene contains AP‐1 binding sites. We examined in C6 glioma cells the effect of VPA on 5‐HT2A receptor signaling. Treatment of cells with VPA (100 µg/mL) for 20 h, but not 1.5 h, resulted in an enhancement of 5‐HT2A receptor‐stimulated PI hydrolysis. This effect of 20‐h VPA exposure appeared not to be at the level of G protein or effector (i.e. phospholipase C: PLC) as inositol phosphate accumulation stimulated by aluminum fluoride or the PLC activator 2,4,6‐trimethyl‐N‐(m‐3‐trifluromethylphenyl) benzenesulfonamide was not increased. The number of 5‐HT2A receptors, as determined in saturation binding experiments using [3H]ketanserin, was increased by 20‐h VPA treatment, with no change in affinity (KD). Taken together, our data suggest that the increase in 5‐HT2A receptor‐mediated PI hydrolysis following 20‐h VPA exposure is not due to a general effect of VPA on this signaling cascade, but due to the up‐regulation of 5‐HT2A receptor number.
Validity and reliability of the revised convergence insufficiency symptom survey in adults
Authors: Rouse Michael W. , Borsting Eric J. , Lynn Mitchell G. , Scheiman Mitchell , Cotter Susan A. , Cooper Jeffrey , Kulp Marjean T. , London Richard , Wensveen Janice ,   Convergence Insufficiency Treatment Trial Group
Published: August 2004

Purpose:  To assess the validity and reliability of the revised Convergence Insufficiency Symptom Survey (CISS) in adults aged 19–30 years. The CISS was developed to be the primary outcome measure for studies evaluating various treatments for convergence insufficiency (CI).

Methods:  CISS mean scores from adults with symptomatic CI and adults with normal binocular vision (NBV) were compared to assess the survey's validity. Adults with symptomatic CI were given the CISS twice to evaluate reliability, which was assessed using intraclass correlation coefficient (ICC) and 95% limits of agreement.

Results:  Forty‐six adults with CI and 46 adults with NBV participated in the study. The mean CISS score for the CI group was 37.3 (S.D. = 9.3) and 11.0 (S.D. = 8.2) for the NBV group. These mean values were significantly different (p < 0.0001). Good discrimination (sensitivity = 97.8%, specificity = 87%) was obtained using a score of 21 or higher. For the CI group the ICC was 0.885 (95% CI of 0.798, 0.936) and the 95% limits of agreement were −9.0 to 7.6.

Conclusions:  Adults with symptomatic CI had a significantly higher CISS score than adults with NBV. The results of the study demonstrate that the CISS is a valid and reliable instrument that can be used clinically or as an outcome measure for research studies of adults with CI.
A comparison of the ARK‐700A autokeratometer and Medmont E300 corneal topographer when measuring peripheral corneal curvature
Authors: González‐Méijome J. M. , Jorge J. , Queiros A. , Almeida J. B. , Parafita M. A.
Published: August 2004

Purpose:  The purpose of this study was to evaluate if corneal topogometry measurements as taken with the ARK‐700A autokeratometer are comparable with those measured by the Medmont E300 videokeratoscope at corresponding locations.

Methods:  Central and peripheral radius and eccentricity were measured in 122 right eyes of young normal subjects using autokeratometry and videokeratoscopy, obtained in a random order.

Results:  Curvature measurements obtained with the ARK700A and Medmont E300 correlated well for the central cornea. Larger differences were observed between peripheral autokeratometry readings and the empirically determined corresponding locations with the videokeratoscope. Correlations between the instruments are inconsistent, resulting in unacceptable confidence intervals. Corneal eccentricity was significantly different between the instruments for the vertical (t = 2.4; p = 0.018) and for the horizontal meridians. In the first case, the difference between the averaged values was not clinically significant, but in the horizontal meridian the AK significantly overestimated eccentricity values (t = −11.5; p < 0.001) with differences which were clinically significant.

Conclusions:  Central corneal curvature data obtained by ARK700A and Medmont E300 can be interchanged but the same is not true of peripheral determinations of corneal shape. ARK700A probably measures peripheral corneal shape within an elliptical region between 5 and 7 mm in diameter, with the major axis in the vertical meridian.
Relation between static and dynamic aspects of vergence, estimated with a subjective test using flashed dichoptic nonius lines
Authors: Jaschinski Wolfgang
Published: August 2004

The psychophysical technique for measuring vergence with dichoptic nonius lines was used to investigate dynamic responses to step vergence stimuli. Liquid crystal shutter glasses were operated with a cathode ray tube monitor to present convergent or divergent step stimuli of 32 min arc at t = 0. The resulting initial vergence response was estimated with nonius lines that appeared for 80 ms at a fixed delay of 400 ms after the vergence step stimulus. The vergence state reached 400 ms after the step depended on the vergence accuracy assumed before the step, i.e. baseline fixation disparity (FD). The following physiologically plausible results were found: (i) the amount of dynamic vergence changes within 400 ms tended to be negatively correlated between the convergent and divergent direction; (ii) subjects with a smaller convergent dynamic change had a steeper proximity–FD curve measured with static fusion targets as a function of viewing distance; (iii) FD was more eso or more exo depending on whether the vergence change was larger in the convergent or divergent direction respectively.
Influence of corneal asymmetry on the phakometric measurement of ocular surface alignment
Authors: Cervino A. , Uppal H. , Dunne M. C. M.
Published: August 2004

Phakometric measurements of corneal and crystalline lens surface alignment are influenced by corneal asymmetry in which the corneal apex does not coincide with the limbal centre. The purpose of this study was to determine the horizontal separation (e) between these corneal landmarks. Measurements were made in 60 normal eyes (30 subjects) using the Orbscan IIz corneal analysis workstation. Our results show that both corneal landmarks typically coincide, so that e = 0, but that inter‐subject variations of about ±1 mm can be expected (so that the corneal apex may fall nasal or temporal to the visual axis). This suggests that no correction for corneal asymmetry is required when estimating average amounts of ocular alignment from samples of eyes but that the measurement of e is strongly recommended for measurements in individual eyes.
Comparison of aberrations in different types of progressive power lenses
Authors: Villegas Eloy A. , Artal Pablo
Published: August 2004

Recently, computer numerically controlled machines have permitted the manufacture of progressive power lenses (PPLs) with different designs. However, the possible differences in optical performance among lens designs are not yet well established. In this work, the spatially resolved aberrations, at 20 relevant locations, of three PPLs with different designs were measured with a Hartmann–Shack wavefront sensor. The wavefront aberration (WA), its root mean square error (RMS) and the point‐spread function were obtained. Spatially resolved plots are shown for all aberrations, astigmatism alone, and for higher order aberrations. The average RMS of all zones is also compared, and the standard deviation is used as a parameter to evaluate the level of hard‐soft design. We find differences in the spatial distribution of the aberrations but not in the global RMS, indicating that current PPLs are rather similar to a waterbed, with the aberrations being the water: they can be moved but they cannot be eliminated.
Repeatability of the Waterloo Four‐Contrast LogMAR Visual Acuity chart and Near Vision Test card on a group of normal young adults
Authors: Cho Pauline , Woo George C.
Published: August 2004

Purposes:  To investigate the repeatability of logMAR visual acuity (VA) with the Waterloo Four‐Contrast LogMAR Visual Acuity (FCLVA) chart and the Near Vision Test (NVT) card. The differences and agreements between near logMAR VA using horizontally‐ and vertically‐presented letters were also determined.

Methods:  Visual acuity of one eye (55 subjects) was first assessed by using the FCLVA chart, comprising four charts of varying contrast, and then with the NVT card (comprising four charts of two contrasts and two presentations). Measurements were repeated after 3 or 4 weeks.

Results:  No significant between‐visit differences were observed for any of the charts used. The repeatability coefficient for the distance 90, 60, 30 and 10% charts were 0.07, 0.11, 0.15 and 0.16 log units, respectively. The repeatability coefficients of the near vision charts were 0.06, 0.04 (high contrast), 0.11 and 0.10 (low contrast) log units. The agreements between horizontally‐ and vertically‐presented letters were good. The differences were similar to the repeatability coefficient of each chart.

Conclusions:  The repeatability coefficient of the high contrast distance and near chart was about half a line. Repeatability coefficients increase with decreasing contrasts for both distance and near charts, with coefficients of one line or more for low contrast charts. Variabilities in both distance and near VA increase with decrease in contrast. The presentation of the letters does not affect near VA and the agreement between horizontally‐ and vertically‐presented letters (both high and low contrast) was within the repeatability coefficient of each chart.
Orbital development in Hong Kong Chinese subjects
Authors: Chau Anson , Fung Karl , Yip Lawrance , Yap Maurice
Published: August 2004

The purpose of this study was to examine the development of the orbit in Hong Kong Chinese subjects. Orbit volume was determined from magnetic resonance images of 81 subjects aged from 1 to 42 years old. Results show that orbit volume ranged from 11.56 to 25.50 cm3. In the first year of life, the mean orbit volume was 12.36 cm3. The orbit showed rapid growth in the first 3 years of life. From about 1–3 years old, the mean volume was 15.31 cm3. The orbit grew steadily to the age of 10 years. From age 11 to 15 years old, the mean volume was 20.24 cm3. Orbit growth levelled off at about 16 years of age with the mean volume at 21.00 cm3.
Spatial load factor in prediction of reading performance
Authors: Larter S. C. , Herse P. R. , Naduvilath T. J. , Dain S. J.
Published: August 2004

This study investigated whether there is a relationship between reading age and clinical optometric tests that have varying degrees of spatial loading in their design. Spatial loading in this context is the demand on the visual system to process information about the relative position and orientation of stimuli. A total of 112 children aged 8–11 years were assessed using saccadic eye movement and rapid naming tasks with varying spatial loads. All were subtests of Garzia's Developmental Eye Movement test and Liubinas’ SeeRite Reading Diagnostic Programme. Variability in load was achieved by comparing rapid naming of numerals vs the spatially loaded letters p, d, b, q; and by comparing the speed of reading numerals presented in increasingly complex arrays. Reading Age was assessed independently and results were analysed by multiple logistic regression. Spatially loaded naming tasks performed at speed exposed a Spatial Loading Factor which clearly differentiates children at risk with reading.
RAF Near Point Rule modification
Authors: Adler Paul
Published: August 2004

A simple and inexpensive modification to the RAF near point rule is described. This modification allows a greater range of values for near point of convergence to be measured.
Pseudophakic accommodation with translation lenses – dual optic vs mono optic
Authors: Langenbucher Achim , Reese Sven , Jakob Christina , Seitz Berthold
Published: August 2004

Purpose:  To investigate the pseudophakic accommodation effect in dual and mono optic translation accommodative intraocular lenses (AIOL) using linear matrix methods in the paraxial space.

Methods:  Dual (anterior optic of power +32 D linked to a compensatory posterior optic of negative power) and mono lens power was determined in the non‐accommodated state using linear geometric optics based on the Gullstrand model eye. The position of the AIOL was calculated from a regression formula. Pseudophakic accommodation was assessed with three systems: (1) forward shift of the mono optic lens, (2) anterior translation of the anterior optic in the dual optic lens system with an unchanged position of the posterior minus lens and (3) symmetrical anterior and posterior translation of the anterior and posterior lens. The Gullstrand model eye was modified by changing the axial length (and proportionally changing the phakic anterior chamber depth) to investigate the accommodative effect in myopic and hyperopic eyes.

Results:  The dual optic lens system (2) yields a nearly constant accommodation amplitude of 2.4–2.5 D mm−1 movement over the total range of axial lengths. The mono optic lens (1) provides a higher accommodative effect only in extremely short eyes (high refractive power of the lens), whereas for normal eyes (1.4–1.5 D mm−1 movement) and for long (myopic) eyes the accommodative effect is much less than the dual optic lens. The dual optic lens system under condition (3) yields less accommodation amplitude compared with the dual optic system under condition (2) over the total range of axial length but provides higher accommodation amplitude compared with the mono optic lens system (1) with axial lengths greater than 22.3 mm (lens power 25.5 D). In the accommodated state, with lens translation of 1 mm, the absolute value of the lateral magnification increases with the refractive power of the mono optic lens (1) and decreases in both dual optic lens systems (under conditions 2 and 3).

Conclusions:  A mathematical strategy is presented for calculation of the accommodative effect of mono‐optic and dual optic AIOL. The dual optic lens yielded a nearly constant accommodation amplitude of about 2.4–2.5 D mm−1 translation, whereas the mono optic lens yielded an accommodative response of <2 D mm−1 translation in long myopic or normal eyes. Only in extremely short eyes is the accommodative amplitude of the mono‐optic lens higher than the dual optic lens.
Clinical characteristics of unilateral myopic anisometropia in a juvenile optometric practice population
Authors: Pointer Jonathan S. , Gilmartin Bernard
Published: August 2004

Purpose:  A retrospective study of longitudinal case histories, undertaken to establish the clinical and statistical characteristics of unilateral myopic anisometropia (UMA) amongst the juvenile and adolescent population at an optometric practice, is reported. UMA was defined as that specific refractive state where an unequivocally myopic eye is paired with a ‘plano’ [spherical equivalent refraction, (SER) = ±0.25 Dioptres (D)] companion eye.

Methods:  The clinical records of all patients aged <19 years on file at an established independent optometric practice were categorised as ‘myopic’ (SER ≤−0.50 D), ‘hypermetropic’ (≥+0.75 D) or ‘emmetropic’ (≥−0.37≤+0.62 D). Subsequently all juvenile patients matching the UMA criterion, together with a case‐matched group of bilaterally myopic individuals, were selected as the comparative study populations.

Results:  A total of 14.4% (n = 21 of 146) of the juvenile myopic case histories were identified as cases of UMA. More than half of these UMA cases emerged between the ages of 11.5 and 13.5 years. There was a marked female gender bias. The linear gradient of the age‐related mean refractive trend in the myopic eye of the UMA population was not statistically significantly different (p > 0.1) to that fitted to the ametropic progression recorded in either eye of the case‐matched population of young bilateral myopes; uniquely the slope associated with the companion eye of UMA cases was statistically significantly (p < 0.025) less steep. Compared with bilateral myopes fewer cases of UMA required a refractive correction to relieve visual or asthenopic symptoms, and this initial correction was dispensed on average 1 year later (at age 12.7 years) in UMA patients.

Conclusions:  Individuals identified as demonstrating clinically‐defined UMA can be considered as distinct but functionally normal cases on the continuum of human refractive error. However, any unilaterally‐acting determining factor(s) underlying the genesis of the condition remain obscure.
Influence of surround illumination on pupil size and contrast sensitivity
Authors: Vizmanos Juan G. , De La Fuente Isabel , Matesanz Beatriz M. , Aparicio Juan A.
Published: August 2004

Lighting plays a major role in contrast sensitivity (CS) measurements. Both the test and surround illumination influence the results although they are not usually considered in clinical practice. The effects of test luminance are well known, but the influence of surround luminance seems to be less investigated. This study aims to evaluate the differences in CS measured with two configurations of surround illumination typical of clinical practice; and to analyse the influence of the angular size of the target on pupil diameter for both surround luminances. An experimental arrangement was designed to measure CS with controlled illumination of both test and surround. An infrared pupillometer was also used to measure steady pupil size. A statistically significant increase of CS and a decrease of pupil size with higher surround illumination were found.
A Global Ranking of Political Science Departments
Authors: Hix Simon
Published: August 2004

Rankings of academic institutions are key information tools for universities, funding agencies, students and faculty. The main method for ranking departments in political science, through peer evaluations, is subjective, biased towards established institutions, and costly in terms of time and money. The alternative method, based on supposedly ‘objective’ measures of outputs in scientific journals, has thus far only been applied narrowly in political science, using publications in a small number of US-based journals. An alternative method is proposed in this paper – that of ranking departments based on the quantity and impact of their publications in the 63 main political science journals in a given five-year period. The result is a series of global and easily updatable rankings that compare well with results produced by applying a similar method in economics.
Semi-Presidentialism: Concepts, Consequences and Contesting Explanations
Authors: Elgie Robert
Published: August 2004

In contrast to the work on presidentialism and parliamentarism, semi-presidentialism remains very much the poor relation in the debate about regime types. This is true both in the sense that there is less work on semi-presidential regimes and also because of the fact that semi-presidentialism has few advocates. This review examines the existing work on semi-presidentialism and asks three questions: What is semi-presidentialism? What is the main dependent variable in semi-presidential studies? And what is the most appropriate explanatory variable in such studies' It does provide some answers to these questions, but the main purpose is to highlight some of the most problematic issues in the contemporary study of semi-presidentialism.
A Randomized, Controlled Trial of Comprehensive Geriatric Assessment and Multidisciplinary Intervention After Discharge of Elderly from the Emergency Department—The DEED II Study
Authors: Caplan Gideon A. , Williams Anthony J. , Daly Barbra , Abraham Ken
Published: August 2004

Objectives: To study the effects of comprehensive geriatric assessment (CGA) and multidisciplinary intervention on elderly patients sent home from the emergency department (ED).

Design: Prospective, randomized, controlled trial with 18 months of follow‐up.

Setting: Large medical school–affiliated public hospital in an urban setting in Sydney, Australia.

Participants: A total of 739 patients aged 75 and older discharged home from the ED were randomized into two groups.

Intervention: Patients randomized to the treatment group underwent initial CGA and were followed at home for up to 28 days by a hospital‐based multidisciplinary outreach team. The team implemented or coordinated recommendations. The control group received usual care.

Measurements: The primary outcome measure was all admissions, to the hospital within 30 days of the initial ED visit. Secondary outcome measures were elective and emergency admissions, and nursing home admissions and mortality. Additional outcomes included physical function (Barthel Index (total possible score=20) and instrumental activities of daily living (/12) and cognitive function (mental status questionnaire (/10)).

Results: Intervention patients had a lower rate of all admissions to the hospital during the first 30 days after the initial ED visit (16.5% vs 22.2%; P=.048), a lower rate of emergency admissions during the 18‐month follow‐up (44.4% vs 54.3%; P=.007), and longer time to first emergency admission (382 vs 348 days; P=.011). There was no difference in admission to nursing homes or mortality. Patients randomized to the intervention group maintained a greater degree of physical and mental function (Barthel Index change from baseline at 6 months: −0.25 vs −0.75; P<.001; mental status questionnaire change from baseline at 12 months: −0.21 vs −0.64; P<.001).

Conclusion: CGA and multidisciplinary intervention can improve health outcomes of older people at risk of deteriorating health and admission to hospital. Patients aged 75 and older should be referred for CGA after an ED visit.
Use of the Physician Orders for Life‐Sustaining Treatment Program in Oregon Nursing Facilities: Beyond Resuscitation Status
Authors: Hickman Susan E. , Tolle Susan W. , Brummel‐Smith Kenneth , Carley Margaret Murphy
Published: August 2004

Objectives: Program was designed to communicate resident/surrogate treatment preferences in the form of medical orders. To assess statewide nursing facility use of the Physician Orders for Life‐Sustaining Treatment (POLST) and to identify the patterns of orders documented on residents' POLST forms.

Design: Telephone survey; on‐site POLST form review.

Setting: Oregon nursing facilities.

Participants: One hundred forty‐six nursing facilities in the telephone survey; 356 nursing facility residents aged 65 and older at seven nursing facilities in the POLST form review.

Measurements: A telephone survey; onsite POLST form reviews.

Results: In the telephone survey, 71% of facilities reported using the POLST program for at least half of their residents. In the POLST form review, do‐not‐resuscitate (DNR) orders were present on 88% of POLST forms. On forms indicating DNR, 77% reflected preferences for more than the lowest level of treatment in at least one other category. On POLST forms indicating orders to resuscitate, 47% reflected preferences for less than the highest level of treatment in at least one other category. The oldest old (≥85, n=167) were more likely than the young old (65–74, n=48) to have orders to limit resuscitation, medical treatment, and artificial nutrition and hydration.

Conclusion: The POLST program is widely used in Oregon nursing facilities. A majority of individuals with DNR orders requested some other form of life‐extending treatment, and advanced age was associated with orders to limit treatments.
The Physician Orders for Life‐Sustaining Treatment Program: Oregon Emergency Medical Technicians' Practical Experiences and Attitudes
Authors: Schmidt Terri A. , Hickman Susan E. , Tolle Susan W. , Brooks Heather S.
Published: August 2004

Objectives: To evaluate emergency medical technicians' (EMTs) experiences with the Physician Orders for Life‐Sustaining Treatment (POLST) program and learn about attitudes regarding its effectiveness.

Design: Anonymous survey mailed to a stratified random sample.

Setting: Tri‐County Portland, Oregon, area.

Participants: A total of 572 Oregon EMT respondents (out of 1,048 surveys) were included in the analysis.

Measurements: Survey questions about experiences with the POLST form and opinions about POLST.

Results: Respondents were mostly male (76%) and paramedics (66%). Most respondents (73%) had treated a patient with a POLST, and 74% reported receiving education about POLST. EMTs reported that POLST, when present, changed treatment in 45% of cases. Seventy‐five percent of the respondents agreed that the POLST form provides clear instructions about patient preferences, and 93% agreed that the POLST form is useful in determining which treatments to provide when the patient is in cardiopulmonary arrest. Fewer (63%) agreed that the form is useful in determining treatments when the patient has a pulse and is breathing.

Conclusion: Most respondents have experience with the POLST program. EMTs find the POLST form useful and often use it to change treatment decisions for patients.
Effect of Vascular Lesions on Cognition in Alzheimer's Disease: A Community‐Based Study
Authors: Riekse Robert G. , Leverenz James B. , McCormick Wayne , Bowen James D. , Teri Linda , Nochlin David , Simpson Kate , Eugenio Charisma , Larson Eric B. , Tsuang Debby
Published: August 2004

Objectives: To investigate whether clinical and neuropathological differences exist between Alzheimer's disease (AD) cases with and without vascular lesions neuropathologically diagnosed using Consortium to Establish a Registry for Alzheimer's Disease (CERAD) criteria.

Design: Descriptive observational study.

Setting: A community‐based registry that identified incident dementia cases.

Participants: Of the 124 subjects with available clinical and neuropathological assessments, 30 had AD lesions alone, and 18 had AD with vascular lesions. Patients with other neuropathological findings were excluded.

Measurements: Dependent measures included demographic, clinical, and neuropathological characteristics. Neuropathological diagnoses were made using the CERAD criteria and Braak and Braak staging.

Results: Of the 124 autopsied cases, 85 cases were diagnosed with neuropathological AD. Of these, 30 had pathology consistent with “pure” AD, whereas 18 had AD pathology with significant vascular lesions (AD/V). There were no differences in age, sex, or education between groups. AD/V cases had higher baseline and final Mini‐Mental State Examination (MMSE) scores than pure AD cases, but after adjusting for education, differences in MMSE scores were not statistically significant. The AD/V group had significantly lower Braak staging than the pure AD group, after adjusting for education and final MMSE scores.

Conclusion: In this comparison study of AD cases with and without vascular lesions, AD/V cases had less severe AD pathology than those with AD alone, indicating that cerebrovascular disease likely contributes to the severity of cognitive impairment in those with AD. Controlling for vascular risk factors in patients with AD may have a significant effect on severity of dementia.
The Effect of Risperidone on Nursing Burden Associated with Caring for Patients with Dementia
Authors: Frank Lori , Kleinman Leah , Ciesla Gabrielle , Rupnow Marcia F. T. , Brodaty Henry
Published: August 2004

Objectives: To compare risperidone treatment with placebo for the burden to nursing staff of older nursing‐home residents with dementia.

Design: Randomized, double‐blind, placebo‐controlled trial.

Setting: Long‐term care institutions in Australia and New Zealand.

Participants: Two hundred seventy‐nine residents had evaluable data for comparison of oral risperidone with placebo treatment at 4 weeks, 8 weeks, and endpoint across the 12‐week trial.

Measurements: The Modified Nursing Care Assessment Scale (M‐NCAS) is a 28‐item instrument that measures behavior occurrence in patients (patient outcome) and difficulty of those behaviors for nursing staff as rated by nurse carers (nurse outcome). Treatment groups were compared via analysis of covariance (ANCOVA). To aid score interpretation, M‐NCAS effect sizes were examined by response category, with response defined as subjects with mean Cohen‐Mansfield Agitation Inventory total aggression subscale score change of 4 points or greater, a clinical outcome for patients.

Results: Between‐group ANCOVAs showed statistically significant reductions in nurse‐rated M‐NCAS scores from baseline to endpoint for the patients randomized to risperidone relative to placebo (P<.05). Effects were evident at 4 weeks and maintained over time. Effect sizes were moderate to large for responders and near zero for nonresponders.

Conclusion: Risperidone treatment was associated with an early and sustained reduction in nursing staff burden as measured using the M‐NCAS compared with placebo treatment for older nursing home residents with dementia.