bluuebunny/crossref_metadata_2025 huggingface dataset:
SUCCESSFUL LONG TERM ERADICATION OF FACTOR VIII INHIBITOR IN PATIENTS WITH ACQUIRED HAEMOPHILIA A IN SAUDI ARABIA
Authors: Zaher Galila F , Adam Soheir S
Published: April 2012

Acquired haemophilia A is a serious and potentially fatal bleeding disorder. Diagnosis is difficult and maybe delayed due to its rarity. The high mortality rate and the complex nature of treatment necessitate patient management at a haemophilia centre, where the required expertise and resources are available. Prompt diagnosis is crucial and early initiation of therapy could be life saving. Management includes initial control of bleeding followed by an approach to eradicate the coagulation factor inhibitor. In this paper we describe our local experience with acquired haemophilia A, which resulted in the successful control of major bleeding at presentation and eradication of inhibitors.
A deep chlorophyll maximum nourishes benthic filter feeders in the coastal zone of a large clear lake
Authors: Malkin Sairah Y. , Silsbe Greg M. , Smith Ralph E. H. , Howell E. Todd
Published: April 2012

Water column profiles demonstrated that a deep chlorophyll maximum (DCM) in the littoral zone of Lake Ontario intersected the benthos during the development of stratification. We hypothesized that elevated food supply near the lake bottom may be nourishing littoral‐zone benthic suspension feeders during this time. Chlorophyll fluorescence was monitored at three heights above the lake bottom, together with near‐bottom water velocity using down‐facing acoustic Doppler current profilers (ADCPs), at three coastal stations along a cross‐shore transect. Concurrently, growth rates of quagga mussels (Dreissena bugensis) caged at the lake bottom were compared with mussels suspended 2 m above the bottom. Over a 3‐month period beginning April, caged lake‐bottom mussels grew rapidly (mean biomass‐specific growth rate = 1.08 yr−1), while over a 3‐month period beginning July, bottom mussels experienced a decrease in biomass (−0.74 yr−1). Suspended mussels always grew significantly faster than bottom mussels (2.3 and 2.2 yr−1 in Apr and Jul experiments, respectively), affirming previously predicted growth inhibition on the lake bottom due to seston depletion. The different growth rate between seasons of the caged‐bottom mussels was most likely attributable to differences in near‐bottom chlorophyll concentrations. There was significantly higher chlorophyll a concentration near the lake bottom during the April experiment (average of two stations closest to shore = 2.7 µg L−1) relative to the July experiment (0.21 µg L−1 at the same stations). We suggest that littoral‐zone quagga mussels are nourished during the onset of stratification via development of a DCM.
Existence of an Exact Walrasian Equilibrium in Nonconvex Economies
Authors: D’Agata Antonio
Published: April 2012

The existence of an exact Walrasian equilibrium in nonconvex economies is still a largely unexplored issue. This paper shows that such an equilibrium exists in nonconvex economies by following the ‘nearby economy’ approach introduced by Postlewaite and Schmeidler (Approximate Walrasian Equilibrium and Nearby Economies, 1981) for convex economies. More precisely, the paper shows that any equilibrium price of the convexified version of a nonconvex economy is an equilibrium price also for a set of ‘perturbed’ economies with the same number of agents. It shows that in this set there are economies that differ from the original economy only as regards preferences or initial endowments.
INCA-CE: a Central European initiative in nowcasting severe weather and its applications
Authors: Kann A. , Pistotnik G. , Bica B.
Published: April 2012

Abstract. The INCA-CE (Integrated Nowcasting through Comprehensive Analysis – Central Europe) project aims at implementing a transnational weather information system as well as applications for different socio-economic sectors to reduce risks of major economic damage and loss of life caused by severe weather. Civil protection and also stakeholders from economic sectors are in a growing need of accurate and reliable short-term weather forecasts. Within INCA-CE, a state-of-the art nowcasting system (INCA) is implemented at weather services throughout the European Union's CE (Central Europe) Programme Area, providing analyses and short term forecasts to the aforementioned end-users. In a coherent approach, the INCA (Integrated Nowcasting through Comprehensive Analysis) system will be adapted for implementation and use in a number of partner countries. Within transregional working groups, the gap between short-term weather information and its downstream activities in hydrological disaster management, civil protection and road management will be bridged and best practice management and measure plans will be produced. A web-based platform for outreach to related socio-economic sectors will initiate and foster a dialogue between weather services and further stakeholders like tourism or the insurance sector, flood authorities for disaster management, and the construction industry for cost-efficient scheduling and planning. Furthermore, the project will produce a compact guideline for policy makers on how to combine structural development aspects with these new features. In the present paper, an outline of the project implementation, a short overview about the INCA system and two case studies on precipitation nowcasts will be given. Moreover, directions for further developments both within the INCA system and the INCA-CE project will be pointed out.
Assessment of fat quality during storage chicken meat
Authors: Tkáčová Jana , Angelovičová Maria
Published: April 2012

The aim of study was assessment of fat quality in chicken meat during storage. The experiment verified the quality of fat as the fat acid number. The experiment was performed on the final fattening type of chickens ROSS 308. Chickens were fed by 2% lucerne meal in feed mixture. The carcass was stored in a freezer box at -18 °C after killing. Fat analysis was carried out after 12 and 15 months of storage. Acid number after 12 months storage was ranged from 5.97 to 8.39 mg KOH.g-1 fat, after 15 months, was ranged from 3.26 to 7.80 mg KOH.g-1 fat. The differences between values ​​of acid number and storage periods of chicken meat (12 and 15 months) was statistically significant (P ≤ 0.05). The results indicate a tendency for increased intensity fat the oxidation processes depending on storage length chicken meat. We recommend to assessment other indicators of chemical changes for example peroxide value for confirmation the hypothesis.
Quantitative and structural changes of testis and semen quality parameters changes caused by peroral administration of diazinon in rats
Authors: Cabaj Michal , Toman Róbert , Adamkovičová Mária , Massányi Peter , Šiška Branislav , Lukáč Norbert , Golian Jozef , Hluchý Sví¤toslav
Published: April 2012

The aim of this study was to find the quantitative and structural changes in the rat testis and changes of semen quality after a diazinon administration. METHODS: Rats received diazinon (99% purity) in thier drinking water (40 mg.l-1) with free access. Age of rats at the beginning of the experiment was 30 days and experiment lasted for next 90 days. The histological samples were evaluated by histological and morphometric methods in light microscopy and the samples of semen were evaluated with CASA method. RESULTS: Disintergation of cellular associations in the seminiferous epithelium, germ cells evacuation into the tubule lumen and thier necrosis were mostly observed. Rarely vacuolisation and cracks of epithelium and fibrotisation of interstitial tissue were noted. Morphometric methods have shown extension of epithelium (P<0,01), reduction of  tubule lumen (P<0,001) and dilatation of blood vessels (P<0,001). In CASA analysis elevation of all parameters were noted, with statistically significant increase of DSL, VSL, ALH. Dilatation of blood vessels will be probably one of the most significant finding in diazinon toxicity because changes in blood flow in the testis are the key factors of accurate physiological function of testis. The epithelium despite the serious disintegration of germ cells associations and release of these necrotised germ cells to the lumen was significantly extended. This fact indicates the self-reparation compensational function. The same tendency (stimulation effects) has been found in all analysed sperm parameters. It supports previous hypothesis. CONCLUSIONS: Diazinon in this design of experiment causes the disintegration of the germinal epithelium cells associations consequently leading to necrosis and release of these cells to the tubule lumen. Dilatation of blood vessels and unknown stimulation effect on sperm quality parameters are two other common effects of diazinon. We concluded that diazinon in our subchronic low dose test causes middle to moderate histological,  morphometric and semen quality changes which were partially compensated with some unknown recovery mechanism. Otherwise, subcellular structures and their functions may be damaged which can lead to subfertility. Further investigation of diazinon is needed for verification of our hypothesis.
Manejo Conservador vrs Quirúrgico con placa volar en pacientes mayores con fractura distal de radio
Authors: Editorial Comité , Koslov Andrey Ferrufino , Fonseca Rene
Published: April 2012

Las fracturas de la región distal de radio constituyen lesiones que se atienden con mayor frecuencia en los servicio de urgencias.(1) El tratamiento conservador era el de elección hasta hace algunos años. Sin embargo se ha visto una tendencia progresiva al tratamiento quirúrgico, debido a los importantes trastornos funcionales que acompañaban a los métodos ortopédicos (2).Objetivo: Se comparo la evolución en pacientes mayores de 50 años con fractura extraarticular distal de radio, manejados con tratamiento conservador vrs. tratamiento quirúrgico con placa volar; atendidos en la Consulta Externa de Ortopedia y Traumatología del Hospital Escuela, desde de Junio del 2009 a Junio del 2010.Métodos: Estudio descriptivo longitudinal, con muestra de 27 pacientes mayores de cincuenta años. Parte de los pacientes fueron manejados con tratamiento conservador, debido a un prolongado tiempo de evolución transcurrido desde el momento de la fractura; y a la vez se estudiaron los pacientes que fueron manejados quirúrgicamente con placa volar; con evaluaciones a los dos y tres meses postratamiento. Se analizaron hallazgos radiológicos, complicaciones, y funcionalidad relacionadas con ambos manejos.Resultados: La mayoría no presentaron alteraciones en la altura y angulación radial en ambos manejos, la perdida de rango articular normal fue la complicación mas reportada, los pacientes manejados con placa volar realizaron sus actividades cotidianas con menor dificultad la las 12 semanas.Conclusión: Los pacientes con manejo quirúrgico presentan menor alteración de parámetros radiológicos, y obtienen mejor grado funcional a las 8 semanas postratamiento debido la movilización precoz y fijación rígida de la fractura.Palabras Claves: Fractura extra articular distal de radio; manejo conservador; manejo quirúrgico; complicaciones; funcionalidad.DOI: http://dx.doi.org/10.5377/rmpm.v13i3.622 Revista de los Postgrados de Medicina UNAH Vol. 13 N° 3 Agosto-Octubre 2010
Tratamiento quirúrgico y complicaciones de lesiones esofágicas; estudio de casos en Hospital Escuela, Honduras
Authors: Editorial Comité , Rivera Martha Ayes , Valiadares Francisco Ayes
Published: April 2012

OBJETIVO: Establecer la prevalencia, el manejo quirúrgico, así como la morbilidad y mortalidad asociadas a lesiones esofágicasPACIENTES Y MÉTODOS. Estudio descriptivo transversal que involucró a los pacientes que ingresaron al Servicio de Urgencias Quirúrgicas del Hospital Escuela entre el 1º de enero de 2008 y el 30 de junio de 2010 con diagnóstico de lesión esofágica. Se aplicó un Instrumento de recolección de datos clínicos y de manejo del paciente. Los resultados se presentan como frecuencias y porcentajes de las variables estudiadas utilizando el sistema de proceso de datos EPI.INFO 3.5.1RESULTADOS. Se incluyeron en el estudio 11 casos de pacientes con lesiones esofágicas que se manejaron en el servicio de urgencias quirúrgicas del Hospital Escuela, la mayoría de los casos se dio en el sexo masculino, con una edad promedio de 29 años. La principal etiología de estas lesiones fue la herida por arma de fuego en el 64% de los casos y secundaria a cuerpos extraños (placa dental) en el 27%. La zona anatómica más afectada fue la porción cervical en un 64% seguida de la torácica; el grado de lesión esofágica más frecuente fue la de grado III manejada en la mayoría de los casos mediante cierre primario. La exclusión esofágica se realizó en el 36.4% de los casos y esto a consecuencia del daño tisular y el grado de contaminación encontrado al momento del procedimiento quirúrgico. Los estudios de imagen realizados para la detección de estas lesiones fueron la radiografía cervical y torácica y el esófagograma, en ninguno de los casos se realizó endoscopia.La principal complicación de estas lesiones fue la mediastinitis que llevó a la muerte a 4 de los pacientes de esta serie.CONCLUSIÓN. Al igual que en otros países las lesiones esofágicas son raras, su sintomatología vaga hace que en ocasiones pasen desapercibidas, sin embargo la alta letalidad de sus complicaciones hace necesario su manejo oportuno.. Establecer la prevalencia, el manejo quirúrgico, así como la morbilidad y mortalidad asociadas a lesiones esofágicas.DOI: http://dx.doi.org/10.5377/rmpm.v13i3.623Revista de los Postgrados de Medicina UNAH Vol. 13 N° 3 Agosto-Octubre 2010
No uso de sonda orogástrica preoperatoria y régimen de alimentación postoperatorio en niños con estenosis hipertrófica de píloro
Authors: Editorial Comité , Anariba Raúl Virgilio , Quiroz Roberto Martínez , Rodríguez Gaspar
Published: April 2012

Palabras claves: estenosis hipertrόfica de piloro; sonda orogástrica; regimen de dietaDOI: http://dx.doi.org/10.5377/rmpm.v13i3.627 Revista de los Postgrados de Medicina UNAH Vol. 13 N° 3 Agosto-Octubre 2010
Prevalencia del Síndrome de HELLP y sus resultados Perinatales en pacientes del Hospital Materno Infantil
Authors: Editorial Comité , Sanchez Julissa Yaneth Andrade , Bustillo María Carolina
Published: April 2012

Palabras clave: sindrome de HELLP; resultados perinatales; complicacionesDOI: http://dx.doi.org/10.5377/rmpm.v13i3.630 Revista de los Postgrados de Medicina UNAH Vol. 13 N° 3 Agosto-Octubre 2010
Prevalencia de TDAH, Relación con Reprobación Escolar y Estado Nutricional en Población Escolar del Distrito Central
Authors: Editorial Comité , Duarte Zeni E , Reyes Eunice , Sosa Alfredo L , Risso Elena , Reyes Américo , Munguia Alejandra , Aguilar Mario
Published: April 2012

Palabras Clave: TDAH; Reprobación Escolar; nutrición DOI: http://dx.doi.org/10.5377/rmpm.v13i3.631 Revista de los Postgrados de Medicina UNAH Vol. 13 N° 3 Agosto-Octubre 2010
Rinoplasia abierta vrs cerrada ventajas y desventajas en el Hospital Escuela en el periodo Febrero 2008-Junio 2010
Authors: Editorial Comité , Rodriquez-Espinoza A , Flores-Guifarro Carlos A , Flores Br
Published: April 2012

Palabras clave: Rinoplastia abierta; Rinoplastia cerrada; deformidad nasal; perforatión septal; desviación nasalDOI: http://dx.doi.org/10.5377/rmpm.v13i3.633Revista de los Postgrados de Medicina UNAH Vol. 13 N° 3 Agosto-Octubre 2010
Uso de la combinación de Propofol-Ketamina para sedación en pacientes sometidos a Cistoscopias
Authors: Editorial Comité , López Franklin René , Amaya Ramón Arcadio , Romero María Guadalupe
Published: April 2012

Palabras clave: propofol; Ketamina; analgesia y sedacionDOI: http://dx.doi.org/10.5377/rmpm.v13i3.637Revista de los Postgrados de Medicina UNAH Vol. 13 N° 3 Agosto-Octubre 2010
Utilidad del Misoprostol Oral en el Tratamiento de Aborto Incompleto. Hospital Escuela
Authors: Editorial Comité , Estrada Ada Ruth , Espinal José Manuel
Published: April 2012

Palabras clave: Misoprostol; aborto incompleto; hemorragia uterinaDOI: http://dx.doi.org/10.5377/rmpm.v13i3.637Revista de los Postgrados de Medicina UNAH Vol. 13 N° 3 Agosto-Octubre 2010
Chronic Periodontal Disease May Influence the Pulp Sensitivity Response: Clinical Evaluation in Consecutive Patients
Authors: Zuza Elizangela Partata , Vanzato Carrareto Ana Luiza , Pontes Ana Emília Farias , Brunozzi Marcelo , Pires Juliana Rico , Toledo Benedicto Egbert Corrêa
Published: April 2012

Purpose. The aim of the present study was to evaluate the clinical response of the pulp in teeth with chronic periodontitis. Methods. Consecutive patients who had been admitted to the Clinics of Periodontology and fulfilled the criteria of inclusion were enrolled from January to December 2007. Ninety-eight single-root teeth from 27 patients with chronic periodontitis were evaluated clinically with regard to clinical attachment level (CAL), probing depth (PD), and gingival recession (REC). After periodontal measurements, Pulpal Sensitivity (PS) was evaluated with the use of a cooling stimulus test. Data was analyzed with Student’s t test and contingency C coefficient. Results. Teeth that responded positively to PS test presented lower values of CAL (7.8 ± 2.8 mm), PD (5.0 ± 2.3 mm), and REC (2.8 ± 1.8 mm) in comparison to those that responded negatively (CAL = 12.0 ± 2.2 mm; PD = 7.9 ± 1.6 mm; REC = 4.1 ± 2.4 mm) (P<0.01, Student’s t test). In addition, significant correlations were observed between PS and periodontal parameters. Conclusions. Within the limits of this study, it could be suggested that the progression of periodontitis may significantly influence the negative pulpal response.
Safety Pin Suture for Management of Atonic Postpartum Hemorrhage
Authors: Mostfa Ali Abdelhamed M. , Zaitoun Mostafa M.
Published: April 2012

Objective. To assess the efficacy of a new suture technique in controlling severe resistant uterine atonic postpartum hemorrhage. Patients and Methods. This is a retrospective observational study that included thirteen women with uterine atony and postpartum bleeding that did not react to usual medical management. All these women underwent compressing vertical suture technique in which the anterior and posterior walls of the uterus were attached so as to compress the uterus. The suture is transfixed at the uterine fundus, thus eliminating the risk of sutures sliding off at the uterine fundus (safety pin suture). Results. safety pin uterine compression suture was a sufficient procedure to stop the bleeding immediately in 92.2% of the women. None of the women developed complications related to the procedure. Conclusion. A new safety pin suture is a simple and effective procedure to control bleeding in patients with treatment-resistant, life-threatening atonic postpartum hemorrhage with the advantage of eliminating the risk of the sutures sliding off at the uterine fundus.
Synthesis of Cobalt-Encapsulated Carbon Nanocapsules Using Cobalt-Doped Fullerene Nanowhiskers
Authors: Matsuura Daisuke , Miyazawa Kun'ichi , Kizuka Tokushi
Published: April 2012

We synthesized cobalt- (Co-) doped C60nanowhiskers (NWs) by applying a liquid-liquid interfacial precipitation method using a C60-saturated toluene solution and 2-propanol with Co nitrate hexahydrate (Co(NO3)3⋅6H2O). Heating the NWs at 873–1173 K produced carbon nanocapsules (CNCs) that encapsulated Co clusters with a hexagonal-closed-packed structure. After heating at 1273 K, the encapsulated Co clusters in CNCs were transformed into orthorhombic Co2C clusters. It was found that Co- and Co2C-encapsulated CNCs can be produced by varying heating temperature.
US Supreme Court to Consider Hearing Significant Stormwater Runoff Decision
Authors: Jennison Julie
Published: April 2012

A Ninth Circuit Court of Appeals case, Natural Resources Defense Council Inc. v. County of Los Angeles [636 F.3d 1235 (9th Cir. 2011)], is being considered by the U.S. Supreme Court for review. The case presents issues of nationwide significance for all operators of municipal separate storm sewer systems (MS4). This case, if allowed to stand and not be overturned by the Supreme Court, could have far‐reaching implications and create confusion for the lower courts in deciding future MS4‐related matters.
Utility Financial and Operational Dashboards: From Prehistoric Reporting to High‐tech Live Updates
Authors: Baird Gregory M.
Published: April 2012

Before the era of smart phones and instant messaging, information was difficult to come by and required manual, hands‐on efforts to first gather the data and then process it to create some form of intelligence that could be used by decision‐makers. Although to a degree the water industry may still rely on some customer feedback, utilities have made huge strides in developing early warning systems to monitor not only their water reliability and quality, but also their financial and operational performance.
Effects of a 10-Week Inspiratory Muscle Training Program on Lower-Extremity Mobility in People with Multiple Sclerosis
Authors: Pfalzer Lucinda , Fry Donna
Published: April 2012

Pulmonary muscle weakness is common in ambulatory people with multiple sclerosis (MS) and may lead to deficits in mobility function. The purpose of this study was to examine the effect of a 10-week home-based exercise program using an inspiratory muscle threshold trainer (IMT) on the results of four lower-extremity physical performance tests in people with MS. The study design was a two-group (experimental-control), pretest-posttest study. Outcome measures consisted of pulmonary function measures including maximal inspiratory pressure (MIP), maximal expiratory pressure (MEP), and maximal voluntary ventilation (MVV), and the following lower-extremity physical performance measures: the 6-Minute Walk (6MW) distance, gait velocity (GV), the Sit-to-Stand Test (SST), the Functional Stair Test (FST), and a balance test (BAL). A total of 46 ambulatory participants (Expanded Disability Status Scale [EDSS] score, 2.0–6.5) with MS were randomly assigned to an intervention group (mean EDSS score, 4.1) that received 10 weeks of home-based inspiratory muscle training or a nontreatment control group (mean EDSS score, 3.2). Of the original 46 participants, 20 intervention group participants and 19 control group participants completed the study. Compared with the control group, the intervention group made significantly greater gains in inspiratory muscle strength (P = .003) and timed balance scores (P = .008). A nonsignificant improvement in 6MW distance (P = .086) was also noted in the IMT-trained group as compared with the control group. This is the first study directly linking improvement in respiratory function to improvement in physical performance function in people with mild-to-moderate disability due to MS.
Cognition and Physical Disability in Predicting Health-Related Quality of Life in Multiple Sclerosis
Authors: Hoogs Marietta , Kaur Sukhmit , Smerbeck Audrey , Weinstock-Guttman Bianca , Benedict Ralph H. B.
Published: April 2012

Many studies have shown that multiple sclerosis (MS) has a significant impact on patient health-related quality of life (HRQOL), but the relative contributions of physical versus cognitive disability are not well established. Most studies have relied on HRQOL outcomes that depend largely on patient mood, life satisfaction, and personal happiness. The Sickness Impact Profile (SIP) is a measure of HRQOL known for its relatively strong emphasis on task completion and activities of daily living. As such, the SIP may be less influenced by depression. We sought to determine the relative influence of physical disability and cognition, above and beyond demographic and disease variables, in predicting HRQOL. Patients (n = 132) and healthy controls (n = 26) underwent complete neuropsychological evaluation using the Minimal Assessment of Cognitive Function in MS (MACFIMS) battery and a series of self-report measures assessing depression, fatigue, and HRQOL. The SIP was also administered. Correlation analysis and group comparisons revealed significant associations between cognition and HRQOL outcomes. Logistic regression models comparing the Expanded Disability Status Scale (EDSS) and cognitive tests in predicting poor physical HRQOL retained both EDSS and Symbol Digit Modalities Test (SDMT) performance, while models predicting poor psychosocial and poor overall HRQOL retained only the SDMT. These findings support cognition as a significant predictor of overall HRQOL, psychosocial HRQOL, and, interestingly, physical HRQOL.
Successful Management of a Neurology Infusion Practice
Authors: Foley John F. , Dunne Anne M.
Published: April 2012

The increasing use of infusible biologic therapies, including the novel monoclonal antibody natalizumab for the treatment of relapsing forms of multiple sclerosis, has elicited much interest among neurologists in the provision of in-office infusions for their patients. An in-office infusion center may offer neurologists a means to provide integrated care for their patients in a familiar and supportive environment. This setting is especially convenient for chronically ill patients, allowing them to receive high-quality care under the direct supervision of their neurologist and facility staff. By administering infusible treatments in a neurology practice rather than referring patients to a hospital or oncology/hematology-based infusion center, the primary neurologist can more closely monitor clinical outcomes, treatment adherence, and the occurrence of adverse effects. In addition, there is greater opportunity for patient interaction and education, which can strengthen relationships with clinical caregivers. This model is also applicable to multispecialty or hospital-based neurology groups desiring to integrate neurology infusion services. In this article, we discuss overall management strategies; staffing and scheduling issues; general coding, billing, and reimbursement methodologies; and additional financial considerations.
A Comprehensive Cost-Effectiveness Analysis of Treatments for Multiple Sclerosis
Authors: Newton Ashley N. , Stica Christina M.
Published: April 2012

The purpose of this study was to examine the cost-effectiveness of four disease-modifying drugs (DMDs) used to treat multiple sclerosis (MS): glatiramer acetate (GA; Copaxone), interferon beta-1a (IFNβ-1a) intramuscular (IM) injection (Avonex), IFNβ-1a subcutaneous (SC) injection (Rebif), and interferon beta-1b (IFNβ-1b) SC injection (Betaseron). Cost-effectiveness analyses are useful in countering the financial uncertainties and treatment efficacy concerns faced by people with MS. We conducted simulation analyses of the principal findings of a 2009 study by Goldberg et al. (Goldberg LD, Edwards NC, Fincher C, et al: Comparing the cost-effectiveness of disease-modifying drugs for the first-line treatment of relapsing remitting multiple sclerosis. J Manag Care Pharm. 2009;15:543–555) to frame the researchers' findings from the perspectives of cost-conscious and cost-neutral MS patients. We found that for the cost-conscious consumer, the ranking of most (1) to least (4) preferred DMDs was 1) IFNβ -1a IM (Avonex), 2) GA (Copaxone), 3) IFNβ-1a SC (Rebif), and 4) IFNβ-1b SC (Beta-seron). For the cost-neutral consumer who places priority on effectiveness over costs, the ranking was 1) IFNβ-1a SC (Rebif), 2) IFNβ-1b SC (Betaseron), 3) GA (Copaxone), and 4) IFNβ-1a IM (Avonex). Future studies could examine cost-effectiveness over extended periods of time (eg, 15–20 years) and more closely examine the cost-effectiveness of natalizumab (Tysabri) relative to the four primary DMDs.
Depression Levels and Interferon Treatment in People with Multiple Sclerosis
Authors: Kim Sonya , Foley Frederick W. , Picone Mary Ann , Halper June , Zemon Vance
Published: April 2012

Multiple sclerosis (MS) is the most common cause of neurologic disease in young and middle-aged adults, and 75% of patients are female. Nearly one in two patients with MS will experience clinically significant depression—approximately three times the prevalence rate in the general population. This study used a cross-sectional approach to examine the link between depression levels and use of interferon medications among individuals with MS. Data were collected from 694 patients of the Multiple Sclerosis Comprehensive Care Center at Holy Name Medical Center in Teaneck, New Jersey. Analysis of variance was used to compare depression scores between patients taking and not taking interferons. Regression analyses with depression scores as the dependent variable were also conducted. The Beck Depression Inventory (BDI) was reduced to a set of dimensions by principal components analysis. Two components were identified, reflecting somatic and cognitive symptoms. The results showed no significant relationship between depression levels and interferon treatment. Significant associations were observed between depression and both age and disability status, with younger, more disabled patients tending to be more depressed.
Step-Length Variability in Minimally Disabled Women with Multiple Sclerosis or Clinically Isolated Syndrome
Authors: Flegel Melanie , Knox Katherine , Nickel Darren
Published: April 2012

Gait is one of the most frequently impaired bodily functions in multiple sclerosis (MS). Determining abnormal parameters of gait in early MS could influence MS treatment and rehabilitation. The purpose of this study was to determine whether increased step-length variability could be detected in minimally disabled patients with MS or clinically isolated syndrome (CIS) using a sensored walkway gait analysis system. Nine participants with MS/CIS and nine age- and gender-matched controls were recruited for this study. MS/CIS participants underwent a neurologic examination, and all participants completed a screening interview. Each participant completed three walks at a self-selected pace and three walks at a brisk pace across the GAITRite walkway (MAP/CIR Inc, Havertown, PA). Mean values for step-length variability, step length, and velocity were calculated for each participant's self-selected and brisk trials. Independent t tests were used to compare MS/CIS participants with controls, and effect sizes were calculated. Step-length variability in the left leg at the self-selected pace was found to be greater in participants with MS/CIS than in controls, although no significant differences were found in velocity or step length. Step-length variability measurement shows promise in detecting subtle gait dysfunction. Larger, prospective studies exploring step-length variability may determine its clinical viability for detecting subtle gait dysfunction and could lead to improved prognostication of disability progression in MS.
Relapsing-Remitting Multiple Sclerosis Patients' Experience with Natalizumab
Authors: Miller Colleen E. , Karpinski Mary , Jezewski Mary Ann
Published: April 2012

This phenomenological investigation was undertaken to gain a better understanding of multiple sclerosis (MS) patients' experience with natalizumab (Tysabri; Biogen Idec Inc, Cambridge, MA) treatment and its impact on their quality of life (QOL). Twenty MS patients who were receiving natalizumab treatment were recruited by the physicians, nurse practitioners, nurses, and social worker of the William C. Baird Multiple Sclerosis Center in Buffalo, New York, between March 2009 and November 2009. Patients were invited to participate if they had relapsing-remitting MS, had received at least six treatments of natalizumab, and could articulate their experience. An interviewer obtained informed consent, gathered basic demographic information, and then tape-recorded the participants' accounts of their experience with natalizumab. The audio-recorded interviews were transcribed and de-identified before being submitted to the investigators for analysis. The Atlas.ti qualitative data analysis program (Scolari, Berlin, Germany) was used to manage the data. Patients found natalizumab easy to tolerate and effective; moreover, they described improvement in their QOL. Patients must weigh the benefits of control of their MS against the increased risk of developing progressive multifocal leukoencephalopathy with natalizumab treatment. Information from this study will be used to educate professionals involved in MS patient care as well as patients and families considering treatment with natalizumab.
Dietary fat types and 4‐year cognitive change in community‐dwelling older women
Authors: Okereke Olivia I. , Rosner Bernard A. , Kim Dae H. , Kang Jae H. , Cook Nancy R. , Manson JoAnn E. , Buring Julie E. , Willett Walter C. , Grodstein Francine
Published: April 2012

Objective:

A study was undertaken to relate dietary fat types to cognitive change in healthy community‐based elders.

Methods:

Among 6,183 older participants in the Women's Health Study, we related intake of major fatty acids (saturated [SFA], monounsaturated [MUFA], total polyunsaturated [PUFA], trans‐unsaturated) to late‐life cognitive trajectory. Serial cognitive testing, conducted over 4 years, began 5 years after dietary assessment. Primary outcomes were global cognition (averaging tests of general cognition, verbal memory, and semantic fluency) and verbal memory (averaging tests of recall). We used analyses of response profiles and logistic regression to estimate multivariate‐adjusted differences in cognitive trajectory and risk of worst cognitive change (worst 10%) by fat intake.

Results:

Higher SFA intake was associated with worse global cognitive (p for linear trend = 0.008) and verbal memory (p for linear trend = 0.01) trajectories. There was a higher risk of worst cognitive change, comparing highest versus lowest SFA quintiles; the multivariate‐adjusted odds ratio (OR) with 95% confidence interval (CI) was 1.64 (1.04–2.58) for global cognition and 1.65 (1.04–2.61) for verbal memory. By contrast, higher MUFA intake was related to better global cognitive (p for linear trend < 0.001) and verbal memory (p for linear trend = 0.009) trajectories, and lower OR (95% CI) of worst cognitive change in global cognition (0.52 [0.31–0.88]) and verbal memory (0.56 [0.34–0.94]). Total fat, PUFA, and trans‐fat intakes were not associated with cognitive trajectory.

Interpretation:

Higher SFA intake was associated with worse global cognitive and verbal memory trajectories, whereas higher MUFA intake was related to better trajectories. Thus, different consumption levels of the major specific fat types, rather than total fat intake itself, appeared to influence cognitive aging. ANN NEUROL 2012;
Accelerating progress in induced pluripotent stem cell research for neurological diseases
Authors: Ito Daisuke , Okano Hideyuki , Suzuki Norihiro
Published: April 2012

In 2006, Yamanaka's group pioneered a method for reprogramming somatic cells by introducing definite transcription factors, which enabled the generation of induced pluripotent stem cells (iPSCs) with pluripotency comparable to that of embryonic stem cells. These iPSCs are attracting considerable attention for their potential in rejection‐tolerance personalized replacement therapy. In recent years, patient‐derived iPSCs have been used to recapitulate the phenotypes of neurological diseases and broaden our understanding of the pathogenesis of many neurological diseases, including those of late onset. It is now expected that iPSCs will serve as an unlimited source of disease‐specific neural cells for use in disease modeling. This review outlines current progress in neurodegenerative disease research involving iPSCs and discusses the potential roles iPSCs may play in helping researchers elucidate the pathological processes of neurodegenerative diseases and in drug discovery and regenerative medicine. Ann Neurol 2012;72:167–174.
Concurrent acute brain infarcts in patients with monocular visual loss
Authors: Helenius Johanna , Arsava E. Murat , Goldstein Joshua N. , Cestari Dean M. , Buonanno Ferdinando S. , Rosen Bruce R. , Ay Hakan
Published: April 2012

Objective:

Embolism from a proximal source to the retinal circulation could be a sign of embolism from the same source to the hemispheric circulation. We sought to determine the frequency of acute brain infarcts on diffusion‐weighted imaging (DWI) in patients with monocular visual loss of presumed ischemic origin (MVL).

Methods:

We retrospectively studied 129 consecutive patients with MVL secondary to retinal ischemia. All patients underwent DWI, comprehensive ophthalmologic and neurologic examination, and diagnostic evaluations for the underlying etiology. Statistical analyses explored univariate and multivariate predictors of DWI evidence of acute brain infarcts.

Results:

DWI revealed concurrent acute brain infarct(s) in 31 of the 129 patients (24%). The probability of positive DWI was higher in embolic versus nonembolic MVL (28 vs 8%, p = 0.04), in MVL characterized by permanent visual loss versus transient symptoms (33 vs 18%, p = 0.04), and in MVL associated with concurrent hemispheric symptoms versus isolated MVL (53 vs 20%, p < 0.01). Patients with positive DWI were more likely to harbor a major underlying etiology as compared to those with normal DWI (odds ratio, 3.7; 95% confidence interval, 1.5–9.4).

Interpretation:

This study demonstrates that MVL does not always represent an isolated disease of the retina; approximately 1 of every 4 patients with MVL demonstrates acute brain infarcts on DWI. Because patients with concurrent brain infarcts are more likely to exhibit a cardiac or vascular source of embolism, imaging evidence of brain injury in patients with MVL may be a useful marker to guide the timing and extent of diagnostic examinations. ANN NEUROL 2012;72:286–293.
Adult polyglucosan body disease: Natural History and Key Magnetic Resonance Imaging Findings
Authors: Mochel Fanny , Schiffmann Raphael , Steenweg Marjan E. , Akman Hasan O. , Wallace Mary , Sedel Frédéric , Laforêt Pascal , Levy Richard , Powers J. Michael , Demeret Sophie , Maisonobe Thierry , Froissart Roseline , Da Nobrega Bruno Barcelos , Fogel Brent L. , Natowicz Marvin R. , Lubetzki Catherine , Durr Alexandra , Brice Alexis , Rosenmann Hanna , Barash Varda , Kakhlon Or , Gomori J. Moshe , van der Knaap Marjo S. , Lossos Alexander
Published: April 2012

Objective:

Adult polyglucosan body disease (APBD) is an autosomal recessive leukodystrophy characterized by neurogenic bladder, progressive spastic gait, and peripheral neuropathy. Polyglucosan bodies accumulate in the central and peripheral nervous systems and are often associated with glycogen branching enzyme (GBE) deficiency. To improve clinical diagnosis and enable future evaluation of therapeutic strategies, we conducted a multinational study of the natural history and imaging features of APBD.

Methods:

We gathered clinical, biochemical, and molecular findings in 50 APBD patients with GBE deficiency from Israel, the United States, France, and the Netherlands. Brain and spine magnetic resonance images were reviewed in 44 patients.

Results:

The most common clinical findings were neurogenic bladder (100%), spastic paraplegia with vibration loss (90%), and axonal neuropathy (90%). The median age was 51 years for the onset of neurogenic bladder symptoms, 63 years for wheelchair dependence, and 70 years for death. As the disease progressed, mild cognitive decline may have affected up to half of the patients. Neuroimaging showed hyperintense white matter abnormalities on T2 and fluid attenuated inversion recovery sequences predominantly in the periventricular regions, the posterior limb of the internal capsule, the external capsule, and the pyramidal tracts and medial lemniscus of the pons and medulla. Atrophy of the medulla and spine was universal. p.Y329S was the most common GBE1 mutation, present as a single heterozygous (28%) or homozygous (48%) mutation.

Interpretation:

APBD with GBE deficiency, with occasional exceptions, is a clinically homogenous disorder that should be suspected in patients with adult onset leukodystrophy or spastic paraplegia with early onset of urinary symptoms and spinal atrophy. ANN NEUROL 2012;72:433–441.
Chondroitin sulfate proteoglycans in demyelinated lesions impair remyelination
Authors: Lau Lorraine W. , Keough Michael B. , Haylock‐Jacobs Sarah , Cua Rowena , Döring Axinia , Sloka Scott , Stirling David P. , Rivest Serge , Yong V. Wee
Published: April 2012

Objective:

Failure of remyelination is a critical impediment to recovery in multiple sclerosis (MS). Chondroitin sulfate proteoglycans (CSPGs) have been reported to accumulate in MS lesions, and we thus examined the functional roles of CSPGs on oligodendrocyte precursor cells (OPCs), oligodendrocytes, and remyelination.

Methods:

We evaluated the expression of CSPGs in lysolecithin‐injected mouse spinal cord, an animal model of demyelination and spontaneous remyelination. The functional impact of CSPGs on OPCs and remyelination was investigated using cultured adult murine and human OPCs and by treating demyelinated mice with xyloside to reduce the CSPG deposition that occurred following injury.

Results:

Early and robust upregulation of CSPGs following lysolecithin‐induced demyelination was cleared during remyelination. In culture, CSPGs anchored onto the substratum reduced the adhesion of mouse and human OPCs and their subsequent morphological differentiation into process‐bearing oligodendrocytes. Soluble CSPGs added to already adherent OPCs reduced the development of processes, whereas the acquisition of mature myelin proteins was unimpeded. Stripe assays of alternating CSPG and control substrata confirmed the nonpermissive nature of CSPGs for OPC adhesion and morphological differentiation. Enzymatic degradation of CSPGs with chondroitinase ABC was sufficient to overcome CSPG‐dependent inhibition of human oligodendrocytes. Finally, in vivo xyloside treatment to reduce CSPG synthesis in lysolecithin‐demyelinated mice increased numbers of OPCs and oligodendrocytes in lesions, and culminated in improved remyelination.

Interpretation:

These results identify CSPGs as a nonpermissive substrate for OPCs and oligodendrocytes, and as a prominent impediment to remyelination. The data suggest the requirement for the neutralization of CSPGs for repair after demyelination. ANN NEUROL 2012;72:419–432.
Neonatal exposure to antiepileptic drugs disrupts striatal synaptic development
Authors: Forcelli Patrick A. , Janssen Megan J. , Vicini Stefano , Gale Karen
Published: April 2012

Objective:

Drug exposure during critical periods of brain development may adversely affect nervous system function, posing a challenge for treating infants. This is of particular concern for treating neonatal seizures, as early life exposure to drugs such as phenobarbital is associated with adverse neurological outcomes in patients and induction of neuronal apoptosis in animal models. The functional significance of the preclinical neurotoxicity has been questioned due to the absence of evidence for functional impairment associated with drug‐induced developmental apoptosis.

Methods:

We used patch‐clamp recordings to examine functional synaptic maturation in striatal medium spiny neurons from neonatal rats exposed to antiepileptic drugs with proapoptotic action (phenobarbital, phenytoin, lamotrigine) and without proapoptotic action (levetiracetam). Phenobarbital‐exposed rats were also assessed for reversal learning at weaning.

Results:

Recordings from control animals revealed increased inhibitory and excitatory synaptic connectivity between postnatal day (P)10 and P18. This maturation was absent in rats exposed at P7 to a single dose of phenobarbital, phenytoin, or lamotrigine. Additionally, phenobarbital exposure impaired striatal‐mediated behavior on P25. Neuroprotective pretreatment with melatonin, which prevents drug‐induced neurodevelopmental apoptosis, prevented the drug‐induced disruption in maturation. Levetiracetam was found not to disrupt synaptic development.

Interpretation:

Our results provide the first evidence that exposure to antiepileptic drugs during a sensitive postnatal period impairs physiological maturation of synapses in neurons that survive the initial drug insult. These findings suggest a mechanism by which early life exposure to antiepileptic drugs can impact cognitive and behavioral outcomes, underscoring the need to identify therapies that control seizures without compromising synaptic maturation. ANN NEUROL 2012;72:363–372
Thalamic Connections of Auditory Cortex in Marmoset Monkeys: Lateral Belt and Parabelt Regions
Authors: de la Mothe Lisa A. , Blumell Suzanne , Kajikawa Yoshinao , Hackett Troy A.
Published: April 2012

The primate auditory cortex is comprised of a core region of three primary areas, surrounded by a belt region of secondary areas and a parabelt region lateral to the belt. The main sources of thalamocortical inputs to the auditory cortex are the medial geniculate complex (MGC), medial pulvinar (PM), and several adjoining nuclei in the posterior thalamus. The distribution of inputs varies topographically by cortical area and thalamic nucleus, but in a manner that has not been fully characterized in primates. In this study, the thalamocortical connections of the lateral belt and parabelt were determined by placing retrograde tracer injections into various areas of these regions in the marmoset monkey. Both regions received projections from the medial (MGm) and posterodorsal (MGpd) divisions of the medial geniculate complex (MGC); however, labeled cells in the anterodorsal (MGad) division were present only from injections into the caudal belt. Thalamic inputs to the lateral belt appeared to come mainly from the MGC, whereas the parabelt also received a strong projection from the PM, consistent with its position as a later stage of auditory cortical processing. The results of this study also indicate that the organization of the marmoset auditory cortex is similar to other primates. Anat Rec, 2012. © 2012 Wiley Periodicals, Inc.
Abnormal Development at Early Postimplantation Stage in Mouse Embryos After Preimplantation Genetic Diagnosis
Authors: Yang Yang , Zeng Yan , Lv Zhuo , Wan Ru , Tong Man , Zhu Hui , Wang Liu , Zhou Zuomin , Zhou Qi , Sha Jiahao
Published: April 2012

Preimplantation genetic diagnosis (PGD) is an established procedure for the genetic analysis of embryos. To assess the effect of the procedure on early embryonic development, we generated a murine experimental system, including mice implanted with biopsied in vitro cultured embryos, control mice implanted with in vitro cultured embryos without biopsy, and mice with naturally conceived embryos. Embryos at the 7.5‐dpc stage were isolated from all three groups and the embryo implantation rate, the survival rate of implanted embryos, and the developmental stage of surviving embryos were carefully assessed and compared among all three groups. We found the implantation rate was similar between biopsied and control group embryos (67.92% vs. 66.67%). However, the survival rate of implanted embryos in the biopsied group (49.31%) was significantly lower than that of the control (60.91%) and normal groups (96.24%) at 7.5 dpc. In addition, the survival rate of control group embryos was significant lower than that of normal group embryos. Classification of the precise developmental stages of randomly selected live implanted embryos at 7.5 dpc revealed no differences among the three groups. Our results indicate that blastomere biopsy does not adversely affect embryo implantation. The PGD procedure, in particular blastomere biopsy, increases the rate of embryo death at 4.5–7.5 dpc, but does not affect the development of surviving 7.5 dpc embryos. Anat Rec, 2012. © 2012 Wiley Periodicals, Inc.