bluuebunny/crossref_metadata_2025 huggingface dataset:
Estimating the tempo and mode of gene family evolution from comparative genomic data
Authors: Hahn Matthew W. , De Bie Tijl , Stajich Jason E. , Nguyen Chi , Cristianini Nello
Published: August 2005

Comparison of whole genomes has revealed that changes in the size of gene families among organisms is quite common. However, there are as yet no models of gene family evolution that make it possible to estimate ancestral states or to infer upon which lineages gene families have contracted or expanded. In addition, large differences in family size have generally been attributed to the effects of natural selection, without a strong statistical basis for these conclusions. Here we use a model of stochastic birth and death for gene family evolution and show that it can be efficiently applied to multispecies genome comparisons. This model takes into account the lengths of branches on phylogenetic trees, as well as duplication and deletion rates, and hence provides expectations for divergence in gene family size among lineages. The model offers both the opportunity to identify large-scale patterns in genome evolution and the ability to make stronger inferences regarding the role of natural selection in gene family expansion or contraction. We apply our method to data from the genomes of five yeast species to show its applicability.
DNA methylation of Sleeping Beauty with transposition into the mouse genome
Authors: Park Chang Won , Kren Betsy T. , Largaespada David A. , Steer Clifford J.
Published: August 2005

The Sleeping Beauty transposon is a recently developed non‐viral vector that can mediate insertion of transgenes into the mammalian genome. Foreign DNA elements that are introduced tend to invoke a host‐defense mechanism resulting in epigenetic changes, such as DNA methylation, which may induce transcriptional inactivation of mammalian genes. To assess potential epigenetic modifications associated with Sleeping Beauty transposition, we investigated the DNA methylation pattern of transgenes inserted into the mouse genome as well as genomic regions flanking the insertion sites with bisulfite‐mediated genomic sequencing. Transgenic mouse lines were created with two different Sleeping Beauty transposons carrying either the Agouti or eGFP transgene. Our results showed that DNA methylation in the keratin‐14 promoter and Agouti transgene were negligible. In addition, two different genomic loci flanking the Agouti insertion site exhibited patterns of DNA methylation similar to wild‐type mice. In contrast, high levels of DNA methylation were observed in the eGFP transgene and its ROSA26 promoter. These results indicate that transposition via Sleeping Beauty into the mouse genome may result in a significant level of de novo DNA methylation. This may depend on a number of different factors including the cargo DNA sequence, chromosomal context of the insertion site, and/or host genetic background.
Identification and characterization of a novel member of murine semaphorin family
Authors: Taniguchi Masahiko , Masuda Tomoyuki , Fukaya Masahiro , Kataoka Hirotaka , Mishina Masayoshi , Yaginuma Hiroyuki , Watanabe Masahiko , Shimizu Takao
Published: August 2005

The semaphorin gene family contains a large number of secreted type or transmembrane type proteins, and some of them function as the repulsive and attractive cues of axon guidance during development. Here we report a novel member of murine class 3 semaphorin genes, semaphorin 3G (Sema3G), mapped on chromosome 14. In adulthood, Sema3G is mainly expressed in the lung and kidney, and a little in the brain. Interestingly, in the adult rodent brain Sema3G is expressed only in the granular layer of the cerebellum, as determined by Northern blot and in situ hybridization analyses. We also found that Sema3G binds Neuropilin‐2, but not Neuropilin‐1, and induces the repulsion of sympathetic axons, but not dorsal root ganglion axons, indicating that Sema3G utilizes Neuropilin‐2 as a receptor to repel specific types of axons.
Proton density and apoplastic domains within soybean nodules in relation to the oxygen diffusion barrier
Authors: BROWN S.M. , CHUDEK J.A. , HUNTER G. , SPRENT J.I. , WALSH K.B. , WURTZ G.
Published: August 2005

A spin‐echo pulse sequence was used to obtain 1H nuclear magnetic resonance microimages of soybean nodules, with resolution to 40 mm and 3D presentation. At an acquisition time (TR) of c. 270 ms and a short echo time (TE) of 8.3 ms, a high proton intensity was detected in infected tissue and vascular strands, relative to the cortex. A longer TE of 15.5 ms was associated with a relatively low proton intensity in infected tissue. Thus protons in infected tissue were characterized by a short T2. Following detopping of the plant, or treatment of the root system with Ar:O2, proton intensity (TE 5.9, TR 120 ms) decreased exponentially in a zone corresponding to the inner cortex‐outer infected region. This result is interpreted as being caused by a loss of water mobility (i.e. increase in viscosity) or a filling of intercellular air spaces with fluid (i.e. loss of air‐water interfaces). The membrane impermeant tracer lucifer yellow was observed to infiltrate from the rhizosphere through the nodule cortex into the infected region in intact nodules of detopped and Ar:O2‐treated, but not control, plants. This result is consistent with the filling of air spaces with fluid following the imposed treatments, allowing infiltration of aqueous tracers. Variation in intercellular air space volume within the inner cortex has been suggested as a mechanism to allow a variable rate of diffusion of O2 into soybean nodules.
Stomatal regulation in a changing climate: a field study using Free Air Temperature Increase (FATI) and Free Air CO2 Enrichment (FACE)
Authors: NIJS I. , FERRIS R. , BLUM H. , HENDREY G. , IMPENS I.
Published: August 2005

This study investigates effects of climate warming (+ 2.5°C ubove ambient) and elevated CO2 concentration (600 μmol mol−1) on the stomatal functioning and the water relations of Lolium perenne, using Free Air Temperature Increase (FATI) and Free Air CO2 Enrichment (FACE). Compared to growth at ambient temperature, whole‐season temperature increase reduced leaf stomatal conductance, but only at the top of the canopy (‐14.6 and ‐8.8% at ambient and elevated CO2, respectively). However, because higher canopy temperature raised the leaf‐to‐air vapour pressure difference, leaf transpiration rate increased (+28% at ambient and +48% at elevated CO2) and instantaneous leaf water use efficiency, derived from short‐term measurements of assimilation and transpiration rate, declined (‐11% at ambient and ‐13% at elevated CO2). Nevertheless, at the stand level, growth at + 2.5°C reduced transpiration due to fewer tillers per plant and a smaller leaf area per tiller. This sparser vegetation was also more closely coupled to the atmosphere and maintained a drier internal microclimate. To assess whether the stomatal behaviour observed in this experiment could be explained by prevailing concepts of stomatal functioning, three models were applied (Cowan 1977; Ball, Woodrow & Berry 1987; Leuning 1995). The latter model accounted for the highest proportion of variability in the data (58%) and was insensitive to CO2 and temperature regime, which suggests that the principles of stomatal regulation are not affected by changes in CO2 or climate.
Estimation of the anatomical, stomatal and biochemical components of differences in photosynthesis and transpiration of wild‐type and transgenic (expressing yeast‐derived invertase targeted to the vacuole) tobacco leaves
Authors: PACHEPSKY L. B. , ACOCK B. , HOFFMAN‐BENNING S. , WILLMITZER L. , FISAHN J.
Published: August 2005

Photosynthesis and transpiration rates of transgenic (expressing yeast‐derived invertase targeted to the vacuole) tobacco (Nicotiana tabacum L.) leaves were, respectively, 50 and 70% of those of a wild type at 20°C, 350 cm3 m−3 CO2 concentration, 450 μmol (photons) m−2 s−1 of light intensity, and 70% relative air humidity. These differences could be attributed: (a) to changes in leaf anatomy and, consequently, to changes in gases diffusion between the cells' surfaces and the atmosphere; (b) to different stomatal apertures, and, for the photosynthesis rate, (c) to the altered CO2 assimilation rate. Our objective was to estimate the relative contributions of these three sources of difference. Measurements on the wild‐type and the transgenic leaf cross‐sections gave values for the cell area index (CAI, cell area surface per unit of leaf area surface) of 15.91 and 13.97, respectively.

The two‐dimensional model 2DLEAF for leaf gas exchange was used to estimate quantitatively anatomical, stomatal and biochemical components of these differences. Transpiration rate was equal to 0.9 for the wild‐type and to 0.63 mmol m−2 s−1 for the transgenic leaf: 24.0% of the difference (0.066 mmol m−2 s−1 was caused by the greater cell area surface in the wild‐type leaf, and 66.0% was caused by a smaller stomatal aperture in the transgenic leaf. Photosynthetic rate was 3.10 and 1.55 μmol m−2 s−1 for the wild‐type and transgenic leaves, respectively. Only 10.3% of this difference (0.16 μmol m−2 s−1) was caused by the difference in CAI, and the remaining 89.7% was caused by altered CO2 assimilation rate.
Occupational hypersensitivity to metal salts, including platinum, in the secondary industry
Authors: Cristaudo A. , Sera F. , Severino V. , De Rocco M. , Di Lella E. , Picardo M.
Published: August 2005

Background:  Exposure to platinum group elements (PGEs) – platinum (Pt), palladium (Pd), rhodium (Rh) and iridium (Ir) – may cause acute toxicity or hypersensitivity with respiratory symptoms, urticaria and (less frequently) contact dermatitis. Our aim was to determine the prevalence and the clinical characteristics of hypersensitivity to platinum salts and to other elements of the platinum group.

Methods:  A total of 153 subjects working in a catalyst manufacturing and recycling factory were examined. The examination consisted of a work exposure and medical questionnaire, physical examination, skin prick test for PGEs and other common aeroallergens, and patch tests for PGEs. Skin prick tests and patch tests were performed with H2[PtCl6], K2[PtCl4], Na2[PtCl6], IrCl3, RhCl3, PdCl2, aqueous solutions at different concentrations.

Results:  Positive prick test reactions to Pt‐salts at various concentrations were found in 22 (14.4%) of 153 workers; eight had simultaneous reactions to all Pt‐salts tested; seven had positive responses to H2[PtCl6] only; four had simultaneous positive reactions to both H2[PtCl6] and K2[PtCl4]; three had positive reactions to H2[PtCl6] and Na2[PtCl6]. Three of 22 had positive reactions to H2[PtCl6] and IrCl3 solutions, two of these had positive reactions to H2[PtCl6], IrCl3 and RhCl3 solutions. Positive patch test reactions to platinum salts at day 2 were seen in two of 153 subjects.

Conclusions:  The results of this study demonstrate that Pt‐salts are important allergens in the catalyst industry and that the clinical manifestations involve both the respiratory system and the skin. Hexachloroplatinic acid should be considered the most important salt to use for skin prick tests.
Characterization of allergen‐specific monocyte‐derived dendritic cells generated from monocytes by a single‐step procedure: effect on naïve and memory T cells
Authors: Takishita T. , Okano M. , Takahashi K. , Yoshino T. , Sugata Y. , Hattori H. , Ohuchi S. , Ogawa T. , Nishizaki K.
Published: August 2005

Background:  Dendritic cells are one of the most potent antigen‐presenting cells and when pulsed with allergen can modulate allergen‐specific T‐cell responses. We sought to establish a single‐step method by which to generate allergen‐specific monocyte‐derived dendritic cells (MoDCs).

Methods:  Dermatophagoides farinae (Df)‐prepulsed MoDCs were generated from monocytes by culturing with Df in the presence interleukin (IL)‐4, granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) and tumour necrosis factor (TNF)‐α simultaneously. Df‐prepulsed MoDC were incubated with autologous naïve and memory T cells in the absence of recall antigen, then proliferation and cytokine production by T cells was determined.

Results:  Generation of allergen‐prepulsed MoDCs was confirmed by examining expression of surface molecules. Df‐prepulsed MoDC selectively induced proliferation of Df‐specific T cells in the absence of recall antigen. Under these conditions, Df‐prepulsed MoDCs augmented but did not alter the cytokine production profile. In addition, Df‐prepulsed MoDCs activated naïve T cells leading to proliferation and selective production of IFN‐γ in allergic patients but not in healthy subjects.

Conclusions:  These results suggest that Df‐prepulsed MoDC generated from monocytes by a simple single‐step manipulation can induce Df‐specific cellular responses from both naïve and memory T cells in the absence of recall antigen, and these cells potentially can be utilized as immune adjuvants in allergen‐specific immunotherapy.
Antibody profiles and self‐reported symptoms to pollen‐related food allergens in grass pollen‐allergic patients from northern Europe
Authors: Ghunaim N. , Grönlund H. , Kronqvist M. , Grönneberg R. , Söderström L. , Ahlstedt S. , Van Hage‐Hamsten M.
Published: August 2005

Background:  Most studies on pollen‐related food allergy have so far focused on the association of birch/weed pollen allergens and plant food allergy. The aim of this study was to elucidate the allergen spectrum among a group of grass pollen‐allergic patients from northern Europe and to relate the results to clinical histories of pollen‐related food allergy.

Methods:  Fifty‐eight grass pollen‐allergic patients answered a questionnaire regarding allergy to foods. Blood samples were taken to test IgE‐reactivity to a large panel of pollen allergens and pollen‐ and nonpollen‐related food allergens using crude allergen extracts and recombinant and native allergens.

Results:  Three different groups of grass pollen‐allergic patients were identified according to their IgE antibody profile: a grass pollen group only (19%), a grass and tree pollen group (29%) and a grass, tree and compositae (pan‐) pollen group (48%). No sensitization to Bet v 1 as well as almost no IgE to plant food was observed in the grass pollen group. In contrast, nearly all patients in the two tree‐related groups had IgE to Bet v 1, which reflected the high frequency of adverse reactions to typical birch‐related food in these groups. Only four patients belonging to the pan‐pollen group displayed IgE to profilin Phl p 12/Bet v 2. Patients in the pan‐pollen group reported significantly more symptoms to food allergens compared with patients in the two other groups. The most frequently reported symptom was the oral allergy syndrome.

Conclusions:  Sensitization to grass pollen alone is rare among grass pollen‐allergic patients from northern Europe. The majority of patients are in addition sensitized to birch (Bet v 1), which seems to be closely related to their pollen‐derived food allergy. The study highlights the advantage of using well‐defined allergen molecules for the diagnosis of cross‐reactivity between pollen and food allergens.
The lived experiences of clinical educators with implications for their preparation, support and professional development
Authors: Higgs Joy , McAllister Lindy
Published: August 2005

The article reports on research into the lived experience of being and becoming a speech pathology clinical educator, and examines implications for the preparation and professional development of clinical educators. The Lived Experience of Being a Clinical Educator Model offers valuable insights into the nature of the role and the realities of clinical educators’ lives. The model comprises six dimensions of being a clinical educator: a sense of self; a sense of relationship with others; a sense of being a clinical educator; a sense of agency; an endeavour to seek dynamic self‐congruence; and growth and development. The model will provide a sound basis for the preparation and professional development of clinical educators, as well as being a useful tool for personally reflecting upon their challenging role as practitioners.
Molecular Genetics of the Neuronal Ceroid Lipofuscinoses
Authors: Mole Sara , Gardiner Mark
Published: August 2005

The neuronal ceroid lipofuscinoses (NCLs) are a group of inherited neurodegenerative disorders characterised by the accumulation of autofluorescent storage material in neurons and other cell types. The clinical features include visual impairment, progressive myoclonic epilepsy, and cognitive decline reflecting progressive neurodegeneration. The NCLs are subdivided into several subtypes according to age of onset, clinical course, and ultrastructure of the storage material. The molecular genetic basis of this group of disorders has recently been clarified. Mutations in the gene encoding a lysosomal enzyme, palmitoyl protein thioesterase (PPT), cause infantile NCL (locus CLN1 on chromosome 1p32) or Haltia‐Santavuori disease. This Finnish disease is characterised ultrastructurally by granular osmiophilic deposits (GRODs). Juvenile‐onset NCL with GRODs also is caused by mutations in PPT. Classic late‐infantile NCL (Jansky‐Bielschowsky disease) is caused by mutations in a gene encoding a pepstatin‐insensitive lysosomal peptidase (CLN2 on chromosome 11p15), and juvenile‐onset NCL (Batten disease) is caused by mutations in a gene encoding a 438‐amino‐acid membrane protein (CLN3 on chromosome 16p12) of unknown function. A locus for Finnish variant late‐infantile NCL, CLN5, has been mapped to chromosome 13q22 and a locus for variant late‐infantile NCL, CLN6, to chromosome 15q21–23. These and further advances will allow the molecular basis of the NCLs to be elucidated and may lead to new strategies for diagnosis and treatment.
The Clinical Pharmacokinetics of the New Antiepileptic Drugs
Authors: Perucca Emilio
Published: August 2005

Summary: Because pharmacokinetics is a major determinant of the magnitude and duration of pharmacologic response, understanding the kinetic properties of the new antiepileptic drugs (AEDs) is essential for the correct use of these compounds in clinical practice. After oral administration, absorption is rapid and relatively efficient for the new AEDs, the most notable exception being gabapentin, whose bioavailability decreases with increasing dosage. None of the new AEDs is extensively bound to plasma proteins except for tiagabine, which is over 95% protein‐bound. The route of elimination differs to an important extent from one compound to another, and elimination half‐lives range from over 30 h for zonisamide to 5–7 h for gabapentin. For all drugs that are metabolized, half‐life is shortened and clearance is increased when patients receive concomitant enzyme‐inducing agents such as barbiturates, phenytoin, and carbamazepine. Lamotrigine metabolism is markedly inhibited by valproic acid, and felbamate may increase the serum levels of most other AEDs. Felbamate, topiramate, and oxcarbazepine may also reduce the efficacy of the contraceptive pill by stimulating its metabolism.
Patients' Understanding of and Adjustment to Epilepsy: Interim Findings from a European Survey
Authors: Baker Gus A. , Jacoby Ann , De Boer Hanneke , Doughty Julie , Myon Eric , Taïeb Charles
Published: August 2005

Summary: The purpose of the study was to discover how much European patients with epilepsy and their carers understand about epilepsy. This article reports the interim results for the first four European countries recruited to the study and includes data collected from 1,920 people with epilepsy and 2,136 carers. Clinical and demographic details and data on understanding of epilepsy were collected using self‐completed questionnaires mailed to members of epilepsy support groups. There were no significant differences between people with epilepsy and carers for scores on the Epilepsy Knowledge Questionnaire, although people with epilepsy were more likely to score in the higher ranges. Higher scorers on the questionnaire were more likely to be better educated, to have lower scores on the impact of epilepsy scales, to have higher scores on the adjustment to epilepsy scale, and were less likely to report feeling stigmatized. The study confirms the findings of previous studies that people with epilepsy are reasonably well informed, although some gaps in their knowledge were evident. A comparison of country differences will be made and multivariate statistical analysis will allow a better understanding of the contribution of knowledge to people's overall adjustment to their condition.
Medical and Surgical Strategies for Epilepsy Care in Developing Countries
Authors: Palmini André
Published: August 2005

Summary: Epilepsy is a major health problem, and there is hope that current international initiatives—epitomized in the “Epilepsy: Out of the Shadows” campaign—will increase the commitment of the general public and health officials to the care of patients. Particularly in developing countries, there is great need for alleviation of the extremely difficult situation of people with epilepsy and their families. Doctors can play their part by adhering to specific medical and surgical strategies aimed at the improvement of epilepsy care in these countries. Included in the former are joining efforts to guarantee a regular distribution of conventional antiepileptic drugs (AEDs), make optimal use of the more easily available AEDs, and improve communication with patients and families at all levels. It is also important to support the creation of local and regional specialized epilepsy centers with the capability to perform presurgical evaluation and epilepsy surgery in many patients with medically refractory seizures. The establishment of such centers in developing countries will face several challenges, including a critical view of technological advances and the need to support well‐trained, creative people who can evaluate and operate on patients with relatively limited resources. This article proposes that the success of such an approach depends on the progressive build‐up of a “critical mass” of specialized people who are trained locally to select or reject epilepsy patients for surgery using the available resources. A stepwise approach to the increasing levels of complexity involved in the evaluation and surgical treatment is proposed, with the expectation that each center will find its level and adhere to its capability.
Corpus Callosotomy in Colombia and Some Reflections on Care and Research Among the Poor in Developing Countries
Authors: Fandiño‐Franky Jaime , Torres M. , Nariño D. , Fandiño Javier
Published: August 2005

Summary: The authors present the results of a series of corpus callosotomies (CCS) in 97 patients performed from 1989 to 1997 at the Hospital Neurologico of the Liga Colombiana Contra La Epilepsia, Cartagena, Colombia. This study demonstrates the feasibility of performing these procedures in the developing world and analyzes the outcome and cost of treatment. Patients with medically intractable secondarily generalized epilepsy, bilateral nonfocal epileptic electroencephalogram (EEG), and absence of progressive encephalopathy were accepted as candidates (patients aged 0–30 years; 62 children, 19 girls and 43 boys, with mean age at surgery of 7·9 years; 35 adults, 19 women and 16 men, with mean age at surgery of 25·8 years). Preoperatively, the mean seizure frequency was 12·1 per day, or 364 per month (range, 0·06–200 per day, 1·8–6000 per‐month). Before surgery, 40% of patients were classified with generalized tonic‐clonic seizures of different etiologies, or cryptogenic seizures; 36% had mixed seizures; 19% had Lennox‐Gastaut Syndrome; and 5% had West Syndrome. Usually, routine EEG, computed tomography, and clinical findings sufficed for the surgical decision. The standard microsurgical technique performed was an anterior two‐thirds CCS by the same surgeon under general anesthesia. In five cases, an additional frontal lobe excision after electrocorticography and subdural electrode monitoring was carried out in the same session. The results were evaluated after a mean follow‐up of 35 months (range, 12–28). Two thirds of patients became seizure‐free or were left with none or some disabling seizures. AED medication was eased slightly after surgery. The complication rate was low. The patients underwent postoperative psychosocial studies and neuropsychological rehabilitation and showed tendencies toward improvement. The direct cost of CCS in U.S. dollars (US$) ranged between 3,137 and 3,995 depending on the preoperative studies. Thus, CCS is well suited for selected patients in developing countries. Thus far, implantation of a vagus nerve stimulator has exceeded our economic possibilities in treating similar patients. Some reflections on care and research among epilepsy patients in developing countries are discussed.
Fast and Sustained Efficacy of Levetiracetam during Titration and the First 3 Months of Treatment in Refractory Epilepsy
Authors: French Jacqueline , Di Nicola Sylvie , Arrigo Celestina
Published: August 2005

Summary:  Purpose: To investigate whether the efficacy of levetiracetam (LEV) is sustained in adult patients with refractory partial seizures over a 3‐month period.

Methods: Treatment effect was assessed in a post hoc analysis by determining the proportion of seizure‐free days during each week of a 3‐month period after the initiation of treatment. Pooled data from three randomized, double‐blind, placebo‐controlled trials (n = 883) were analyzed.

Results: The mean proportion of seizure‐free days was greater in the LEV group than in the placebo group. The difference, which was statistically significant, was observed as early as the first week after the initiation of treatment. It was higher in the first week of treatment and subsequently was maintained for each week over the 3‐month period (p < 0.001 or p = 0.002 at each time point). Patients in the LEV group had on average 74% to 81% days each week without any seizure, compared with 69% to 72% in the placebo group.

Conclusions: LEV is efficient in controlling seizures from the first week of drug initiation, during uptitration, and throughout the first 3 months of treatment. An interesting amplification of efficacy occurs in the first week of therapy, which is intriguing and warrants further investigation.
Seizures Manifesting as an Urge to Defecate, with an Ictal Discharge in the Right Hemisphere
Authors: Koubeissi Mohamad Z. , Crone Nathan E. , Lesser Ronald P.
Published: August 2005

Summary: We report a 47‐year‐old right‐handed woman with simple partial seizures manifesting in part as an urge to defecate shortly after a visual distortion. On at least one occasion, this was followed by head deviation to the left and a secondarily generalized tonic–clonic seizure. The ictal electroencephalogram lateralized to the right hemisphere, suggesting that the ictal urge to defecate may lateralize to this side.
Reflex Seizures in Patients with Malformations of Cortical Development and Refractory Epilepsy
Authors: Palmini André , Halasz Peter , Scheffer Ingrid E. , Takahashi Yukitoshi , Jimenez Angeles Perez , Dubeau François , Andermann Frederick , Paglioli‐Neto Eliseu , Da Costa Jaderson Costa , Rosenow Felix , Fritsch Brita
Published: August 2005

Summary: Purpose:Malformations of cortical development (MCDs) are usually highly epileptogenic, and their hyperexcitability could facilitate the occurrence of reflex seizures. We sought to characterize reflex seizures in patients with MCDs and refractory epilepsy.

Methods:Clinical, electrographic, and neuroimaging data were reviewed in eight patients with MCDs who had reflex seizures reproduced during presurgical evaluation.

Results:All eight patients had both reflex and spontaneous seizures. In six, however, drop attacks or axial myoclonic seizures occurred only upon specific sensory stimulation. Reflex seizures were induced by more than one type of stimulus in most patients, but anatomofunctional correlations could usually be invoked. Six patients had significant intellectual impairment. Surgical resection controlled seizures in two patients.

Conclusions:Reflex seizures in patients with MCDs may be medically refractory and may often manifest as drop attacks or axial myoclonus. Surgical resection of focal lesions can bring reflex seizures under control. Putative mechanisms related to the relatively low frequency of reflex seizures in MCDs are discussed.
Poststroke Epilepsy: Occurrence and Predictors—A Long‐term Prospective Controlled Study (Akershus Stroke Study)
Authors: Lossius Morten I. , Rønning Ole M. , Slapø Geir D. , Mowinckel Petter , Gjerstad Leif
Published: August 2005

Summary:  Purpose: The aims of the study were to assess the occurrence of poststroke epilepsy (PSE) in patients with ischemic strokes, to identify predictors, and to investigate whether treatment in a stroke unit (SU) influenced the long‐term outcomes of epilepsy.

Methods: Patients with PSE, defined as those having two ore more unprovoked epileptic seizures ≥1 week after an ischemic stroke, were identified from a cohort of 484 patients with ischemic strokes. The patients were prospectively assessed 7–8 years after stroke or until death. Different variables were studied to look for possible predictors.

Results: From 484 patients with ischemic strokes, PSE developed in 12 (2.5%) and 15 (3.1%) patients during the first year and 7–8 years after stroke, respectively. Eight (53%) of these patients were treated in a stroke unit (SU), and seven (47%) were treated in a general medical ward (GMW). The mean age of those who developed PSE and those who did not was 74.3 years and 76.3 years, respectively. In a multivariate analysis, a Scandinavian Stroke Scale (SSS) score <30 on admission was a significant predictor for developing PSE [odds ratio (OR), 4.9; p = 0.004).

Conclusions: The prevalence of PSE, 7 to 8 years after an ischemic stroke, was 3.1%. SSS scores <30 on admission were a significant predictor for PSE. Neither treatment in SU versus GMW, cortical location, nor age at onset of stroke seemed to influence the risk of developing PSE.
Suppression of Kindled Seizures by Paracrine Adenosine Release from Stem Cell–Derived Brain Implants
Authors: Güttinger Martin , Fedele Denise , Koch Peter , Padrun Vivianne , Pralong William F. , Brüstle Oliver , Boison Detlev
Published: August 2005

Summary:  Purpose: Stem cells and their derivatives have emerged as a promising tool for cell‐based drug delivery because of (a) their unique ability to differentiate into various somatic cell types, (b) the virtually unlimited donor source for transplantation, and (c) the advantage of being amenable to a wide spectrum of genetic manipulations. Previously, adenosine‐releasing embryonic stem (ES) cells have been generated by disruption of both alleles of adenosine kinase (Adk−/‐). Lack of ADK did not compromise the cells' differentiation potential into embryoid bodies or glial precursor cells. The aim of the present study was to investigate the potential of differentiated Adk−/‐ ES cell progeny for seizure suppression by paracrine adenosine release.

Methods: To isolate paracrine effects of stem cell–derived implants from effects caused by network integration, ES cell–derived embryoid bodies and glial precursor cells were encapsulated into semipermeable polymer membranes and grafted into the lateral brain ventricles of kindled rats.

Results: While seizure activity in kindled rats with wild‐type Adk+/+ implants remained unaltered, rats with adenosine‐releasing Adk−/‐ ES cell–derived implants displayed transient protection from convulsive seizures and a profound reduction of afterdischarge activity in EEG recordings. Long‐term seizure suppression was precluded by limited viability of the encapsulated cells.

Conclusions: We thereby provide a proof‐of‐principle that Adk−/‐ ES cell–derived brain implants can suppress seizure activity by a paracrine mode of action. Adk‐deficient stem cells therefore represent a potential tool for the treatment of epileptic disorders.
Application of Magnetoencephalography in Epilepsy Patients with Widespread Spike or Slow‐wave Activity
Authors: Shiraishi Hideaki , Ahlfors Seppo P. , Stufflebeam Steven M. , Takano Kyoko , Okajima Maki , Knake Susanne , Hatanaka Keisaku , Kohsaka Shinobu , Saitoh Shinji , Dale Anders M. , Halgren Eric
Published: August 2005

Summary:  Purpose: To examine whether magnetoencephalography (MEG) can be used to determine patterns of brain activity underlying widespread paroxysms of epilepsy patients, thereby extending the applicability of MEG to a larger population of epilepsy patients.

Methods: We studied two children with symptomatic localization‐related epilepsy. Case 1 had widespread spikes in EEG with an operation scar from a resection of a brain tumor; Case 2 had hemispheric slow‐wave activity in EEG with sensory auras. MEG was collected with a 204‐channel helmet‐shaped sensor array. Dynamic statistical parametric maps (dSPMs) were constructed to estimate the cortical distribution of interictal discharges for these patients. Equivalent current dipoles (ECDs) also were calculated for comparison with the results of dSPM.

Results: In case 1 with widespread spikes, dSPM presented the major activity at the vicinity of the operation scar in the left frontal lobe at the peak of the spikes, and some activities were detected in the left temporal lobe just before the peak in some spikes. In case 2 with hemispheric slow waves, the most active area was located in the left parietal lobe, and additional activity was seen at the ipsilateral temporal and frontal lobes in dSPM. The source estimates correlated well with the ictal manifestation and interictal single‐photon emission computed tomography (SPECT) findings for this patient. In comparison with the results of ECDs, ECDs could not express a prior activity at the left temporal lobe in case 1 and did not model well the MEG data in case 2.

Conclusions: We suggest that by means of dSPM, MEG is useful for presurgical evaluation of patients, not only with localized epileptiform activity, but also with widespread spikes or slow waves, because it requires no selections of channels and no time‐point selection.
A Comparison of the Ability of a 4:1 Ketogenic Diet and a 6.3:1 Ketogenic Diet to Elevate Seizure Thresholds in Adult and Young Rats
Authors: Nylen Kirk , Likhodii Sergei , Abdelmalik Peter A. , Clarke Jasper , Burnham W. McIntyre
Published: August 2005

Summary: Purpose:The pentylenetetrazol (PTZ) infusion test was used to compare seizure thresholds in adult and young rats fed either a 4:1 ketogenic diet (KD) or a 6.3:1 KD. We hypothesized that both KDs would significantly elevate seizure thresholds and that the 4:1 KD would serve as a better model of the KD used clinically.

Methods:Ninety adult rats and 75 young rats were placed on one of five experimental diets: (a) a 4:1 KD, (b) a control diet balanced to the 4:1 KD, (c) a 6.3:1 KD, (d) a standard control diet, or (e) an ad libitum standard control diet. All subjects were seizure tested by using the PTZ infusion test. Blood glucose and β‐hydroxybutyrate (β‐OHB) levels were measured.

Results:Neither KD elevated absolute “latencies to seizure” in young or adult rats. Similarly, neither KD elevated “threshold doses” in adult rats. In young rats, the 6.3:1 KD, but not the 4:1 KD, significantly elevated threshold doses. The 6.3:1 KD group showed poorer weight gain than the 4:1 KD group when compared with respective controls. The most dramatic discrepancies were seen in young rats.

Conclusions:“Threshold doses” and “latency to seizure” data provided conflicting measures of seizure threshold. This was likely due to the inflation of threshold doses calculated by using the much smaller body weights found in the 6.3:1 KD group. Ultimately, the PTZ infusion test in rats may not be a good preparation to model the anticonvulsant effects of the KD seen clinically, especially when dietary treatments lead to significantly mismatched body weights between the groups.
Apical Ballooning Syndrome in a Postoperative Patient with Normal Microvascular Perfusion by Myocardial Contrast Echocardiography
Authors: Ramakrishna Gautam , Ravi Barugur S. , Chandrasekaran Krishnaswamy
Published: August 2005

Apical ballooning syndrome is classically described as transient left ventricular (LV) dysfunction, marked LV akinesia, and normal or near‐normal coronary arteries. The etiology is unclear and there is limited information based on case reports and small case series. We describe a 35‐year‐old woman who underwent surgical hepatectomy and developed apical ballooning syndrome in the postoperative period. The novel use of myocardial contrast echocardiography (MCE) in this setting demonstrated intact microvascular perfusion and lack of coronary flow‐limiting abnormalities despite apical akinesis. In select patients with similar clinical presentations, performing MCE is safe and may be pursued as an alternative to invasive coronary angiography.
Elongation Index as a New Index Determining the Severity of Left Ventricular Systolic Dysfunction and Mitral Regurgitation in Patients with Congestive Heart Failure
Authors: Yokusoglu Mehmet , Uzun Mehmet , Baysan Oben , Erinc Kursad , Sag Cemal , Ozkan Mustafa , Karaeren Hayrettin , Genc Celal , Isik Ersoy
Published: August 2005

The shape of the left ventricle is an important echocardiographic feature of left ventricular dysfunction. Progression of the mitral regurgitation and consequent left ventricular remodeling is unpredictable in heart failure. Elongation index is an index of left ventricular sphericity. The surface area of the elongated ventricle is larger than that of a spherical one. The objective of this study was to assess the relation between elongation index and the degree of mitral regurgitation along with noninvasive indices of left ventricular function. Thirty‐two patients (21 male, 11 female, mean age: 57 ± 6 yrs) with congestive heart failure and mitral regurgitation were included. Patients were stratified into three groups according to vena contracta width as having mild (n = 11), moderate (n = 11) and severe mitral regurgitation (n = 10). The elongation index (EI) was considered as equal to {[(left ventricular internal area‐measured) − (theoretical area of the sphere with measured left ventricular volume)]/(theoretical area of the sphere with measured left ventricular volume)}. Ejection fractions by the modified Simpson rule, dP/dt and sphericity index (SI) were also recorded. The relationship between (EI), ejection fraction, dP/dt and SI reached modest statistical significance (p < 0.05). When the EI and SI were compared, the correlation was also significant (p < 0.01). The areas under the receiver operator curve of EI and SI for discriminating dP/dt < 1000 mm Hg/s were 0.833 and 0.733, respectively. In conclusion, the elongation, which defines the shape of the left ventricle, might be related to the systolic function of the left ventricle and the degree of the mitral regurgitation. Further studies are needed to demonstrate its use in other clinical entities.
Impact of Policy Shifts on South Asian Carers in the United Kingdom
Authors: Hensel Elizabeth , Krishnan Mya , Saunders Katie , Durrani Nazia , Rose John
Published: August 2005

Abstract  The aim of this study was to assess how the introduction of new service policies in the United Kingdom – such as person‐centered planning and the active development of support networks – was impacting the lives of carers of people with intellectual disability from South Asian backgrounds. Using a semistructured interview schedule, 19 families of South Asian background living in an urban conurbation were interviewed about their service use and needs with respect to providing care for their family member with an intellectual disability. The families experienced material disadvantage, poor health, and did not access services to the same extent as did the general population in the UK. Overall, community participation was low and only two individuals with an intellectual disability had a care plan as outlined in the latest UK government policies. The introduction of these new policies did not appear to have positively impacted the lives of the individuals interviewed in this study. The results were similar to findings of studies in other parts of Britain: that is, the culture of caring and protecting the individual with an intellectual disability, combined with the importance of family life over an outside social life, ran somewhat counter to the underlying principles of current national disability policy (i.e., promoting individual rights and independent living). It is suggested that attempts to implement these policies risks alienating carers of South Asian descent from service providers and their implementation must be done in a culturally sensitively context.
Perceptions of Program Administrators Toward Health Planning for Persons with Intellectual Disabilities: A National Survey in Taiwan
Authors: Lin Jin‐Ding , Yen Chia‐Feng , Loh Ching‐Hui , Chwo Miao‐Ju , Wu Jia‐Ling , Tung Ho‐Jui
Published: August 2005

Abstract  Health planning is an important factor in assuring quality of care for the general population. However, in Taiwan relatively little attention has been given to this with respect to vulnerable groups of people, such as those with intellectual disabilities (ID). Using a structured questionnaire, posted to all disability service programs (n = 157) caring for people with ID, the authors examined the perceptions of directors of service programs for people with ID with respect to health planning and the development of health‐planning issues in their programs. Results indicate that although most respondents agreed with the importance of health planning and concurred with the specific health‐planning issues identified by the authors, there was a gap between perceived importance and satisfaction with how these issues were being dealt. The three greatest gaps were observed in “hearing and vision screenings,”“routine meetings on health issues,” and “regular dental health checkups for the ID population.” Using an opportunity calculation to prioritize the most promising health‐planning areas, the authors found that “emergency planning and practice,”“routine meetings on health management,”“planning for infectious disease control,”“regular oral health checkups,” and “hearing and vision screenings” were the areas with greatest opportunities for further improvement in the programs. Size and auspice of the programs were not correlated to the perceived importance and satisfactions. The authors conclude that Taiwanese health authorities need to more carefully promote health planning for people with ID within disability programs so as to ensure the quality of health care and health promotion for people with ID.
Likelihood ratios increase diagnostic certainty in pulmonary embolism
Authors: Chu Kevin , Brown Anthony FT
Published: August 2005

Pulmonary embolism (PE) is a difficult diagnosis to confirm. The choice of tests has led to a myriad of algorithms. Diagnostic uncertainty can be quantified by the application of the tests’ likelihood ratios (LR). Positive and negative LR enable the conversion of a pretest to a post‐test probability, given a positive and negative test result, respectively. Thus, a pretest probability of <17% and a negative D‐dimer with a negative LR of 0.05 (sensitivity 98%, specificity 40%) lead to a post‐test probability of PE of <1%. Ventilation perfusion (V/Q) scans with a normal, very low, low, intermediate and high probability result have an LR of 0, 0.125, 0.25, 1 and 17, respectively. Also, patients with a V/Q scan result other than normal or high probability still have a post‐test probability of PE from 3 to 65%. Positive and negative computed tomography pulmonary angiograms (CTPA) have an LR of 8.6 and 0.06, respectively (sensitivity 95%, specificity 89%). Patients with a high pretest probability and negative CTPA again still have a post‐test probability of more than 10%. However, as the post‐test probability after one test becomes the pretest probability for the next, test results used cumulatively progressively narrow the gap to a final diagnosis. The post‐test probability after a D‐dimer, V/Q scan, CTPA, leg ultrasound or pulmonary angiography, alone or in any combination or in any order, can be calculated using their LR. Use of LR thus assists in the precise interpretation of test results, such as in complex algorithms for PE.
Epidemiology of unarmed threats in the emergency department
Authors: Knott Jonathan C , Bennett Dianne , Rawet Jennifer , Taylor David McD
Published: August 2005

Objective:  To evaluate the precipitants, subject characteristics, nature and outcomes of unarmed threats in the ED.

Methods:  A 12 month prospective survey of security codes precipitated by an unarmed threat (Code Grey).

Results:  Data were collected on 151 subjects. The Code Grey rate was 3.2/1000 ED presentations. They were most frequent on Saturday and in the late evening/early morning. There were verbal or physical threats of violence made to staff on 104 occasions (69%, 95% confidence interval [CI] 61–76) and a perceived threat of patient self‐harm on 114 occasions (76%, 95% CI 68–82). Median time to be seen by a doctor was 8 min (interquartile range [IQR]: 2–21 min) and median time from presentation to Code was 59 min (IQR: 5–222 min). Sixteen subjects (11%, 95% CI 6–17) had a history of violence, 45 (30%, 95% CI 23–38) were affected by alcohol, 25 (17%, 95% CI 11–24) had used illicit drugs and 79 (52%, 95% CI 44–60) had a significant mental illness contributing to the Code Grey. Seventy‐one patients (47%, 95% CI 39–55) required psychiatric admission, 49 (79%, 95% CI 66–88) involuntarily.

Conclusion:  Acutely agitated subjects pose a threat to themselves and the staff caring for them. The reason for the agitation is multifactorial and the majority arrive in a behaviourally disturbed state requiring early intervention. The times most likely to result in a Code Grey coincide with least available resources: ED and hospital risk management policies must account for this. A coherent approach by ED to this population is required to optimize patient and staff outcomes.
Triage nurses validly and reliably estimate emergency department patient complexity
Authors: Vance Jenny , Sprivulis Peter
Published: August 2005

Objective:  To access the validity and reliability of triage nurse estimates of ED patient complexity.

Methods:  Prospective, single‐blinded evaluation of triage nurse estimates of patient complexity, where a high‐complexity patient is defined as a patient requiring two or more procedures or investigations or consultations. Validity of complexity estimates was assessed by comparison with the number of actual procedures, investigations and consultations requested. Reliability of triage nurse estimates of complexity was assessed by comparison with assessment nurse estimates of complexity.

Results:  The specific proportion of agreement and spearman correlation coefficient of triage nurse estimates of complexity with actual procedure, investigations and consultation use were 0.83 (95% confidence interval [CI] 0.79–0.88) and 0.59 (95% CI 0.51–0.66), respectively. The specific proportion of agreement and kappa of triage nurse estimates of complexity with assessment nurse estimates were 0.80 (95% CI 0.73–0.87) and 0.59 (95% CI 0.47–0.71), respectively.

Conclusions:  Triage nurses make valid and reliable estimates of patient complexity. This information might be used to guide ED work flow and ED casemix system analysis.