15 research outputs found
Sublingual sufentanil (Zalviso) patient-controlled analgesia after total knee arthroplasty: a retrospective comparison with oxycodone with or without dexamethasone
David E van Veen,1 Christiaan CWM Verhelst,2 Roelof T van Dellen,3 JSHA Koopman4 1Erasmus University Rotterdam, Rotterdam, The Netherlands; 2Department of Orthopedic Surgery, Maasstad Hospital, Rotterdam, The Netherlands; 3Department of Hospital Pharmacy, Maasstad Hospital, Rotterdam, The Netherlands; 4Department of Anesthesiology, Maasstad Hospital, Rotterdam, The Netherlands Abstract: Postoperative pain is a major problem, especially in orthopedic surgery. Our data suggest suboptimal pain management after total knee arthroplasty. This study evaluated a sufentanil sublingual tablet system (Zalviso) to optimize postoperative pain treatment. This retrospective, single-center, cohort study was conducted between January 2017 and September 2017. Zalviso as standard treatment was compared with a cohort receiving oxycodone (Oxy) immediate release and Oxy extended release and another receiving Oxy immediate release, Oxy extended release, and dexamethasone (Dexa + Oxy). The primary end point, pain intensity, was assessed on a numeric rating scale (NRS). Highest, lowest, and number of NRS scores >7 were collected. Secondary end points included length of hospital stay, nausea, and mobilization on the day of surgery. Patients receiving Dexa + Oxy had a lower lowest-pain intensity on day 0 (median 0, IQR 0–0) when compared to patients receiving Oxy (median 2, IQR 0–3; P<0.0001) or Zalviso (median 2, IQR 0–4; P<0.0001). No differences were observed on day 1 or 2. No differences were observed in highest pain score or number of patients reporting NRS scores > 7. Patients treated with Dexa + Oxy or Zalviso were discharged earlier compared to patients treated with Oxy (P<0.001). Patients treated with Zalviso experienced more nausea compared to other groups on day 0 and day 1 (P<0.001). Patients treated with Dexa + Oxy had a higher percentage of mobilization on the day of surgery compared to Oxy and Zalviso (P<0.001). In conclusion, Zalviso did not improve postoperative pain management in patients undergoing total knee arthroplasty and increased nausea. Keywords: total knee arthroplasty, postoperative pain, multimodal treatment, acute pain, Zalviso, sublingual sufentanil tablet system, opioid, sufentanil, sublingual formulatio
Comprehensive behavioral testing in the R6/2 mouse model of Huntington's disease shows no benefit from CoQ10 or minocycline
Previous studies of the effects of coenzyme Q10 and minocycline on mouse models of Huntington’s disease have produced conflicting results regarding their efficacy in behavioral tests. Using our recently published best practices for husbandry and testing for mouse models of Huntington’s disease, we report that neither coenzyme Q10 nor minocycline had significant beneficial effects on measures of motor function, general health (open field, rotarod, grip strength, rearing-climbing, body weight and survival) in the R6/2 mouse model. The higher doses of minocycline, on the contrary, reduced survival. We were thus unable to confirm the previously reported benefits for these two drugs, and we discuss potential reasons for these discrepancies, such as the effects of husbandry and nutrition
Stage analysis of the reaction process using brain-evoked potentials and reaction time
Motor processes partly determine reaction time (RT) in both choice reaction time and in binary classification tasks. These latter tasks are popular in cognitive psychology because the experimenter believes that he has kept the motor component simple and constant and therefore can attribute changes in RT to perceptual or cognitive processes. In this paper we used the P3 component of the event-related potential (ERP) as a time marker indicating the duration of perceptual and cognitive processes. The latency of this component is believed to reflect stimulus evaluation time independent of response selection and organization time. Two types of tasks were used: a choice-reaction time task and a binary classification task. Signal similarity and S-R compatibility additively affected RT, but only signal similarity affected P3 latency. The number of items in the positive set and response type affected both P3 latency and RT. Relative response frequency changed the bias in the cognitive evaluation of the stimulus, reflected in the latency of the P3 component, and affected RT only if the subjects preset their motor system (indexed by the late CNV). A model was presented which proposes that motor processes may partially overlap with the perceptual and cognitive evaluation of the stimulus. Both ERPs and RT are necessary tools in the study of the relative timing of these processes
Late positive components and stimulus evaluation time
The amplitude and latency of late positive components were, together with reaction time (RT), studied in a task which combines visual and memory search. The visual display contained either one, two or four letters, as did the memory set. Six load combinations, resulting in one, four, eight and 16 comparisons, were examined. The reaction time data indicated a self-terminating search process. Three late positive components were present in the evoked potential: one at 375 msec after the onset of the display, one at 375 msec after the offset of the display and one around 600 msec. Only the latter component appeared to be sensitive to the number of comparisons. Adaptive averaging was applied to this latter component. The latency of this P300 suggested, in contrast to the RT data, an exhaustive search process. In addition there was a negligible correlation between the response latency and P300 latency at single trial level. Several hypotheses are suggested for what P300 could have to tell us
A review of the Groote Schuur hospital experience of low-velocity non-missile penetrating orbital and transorbital stab wounds
Includes bibliographical references.The aim of this study is to perform a retrospective review of all cases of low-velocity non-missile penetrating orbital trauma with intracranial complications presenting at Groote Schuur Hospital over the 5 year period between 1997 and 2001
On-line Measurement and Modelling of Dynamic Plant Responses to Variations of the Microenvironment
De landbouw staat voor grote uitdagingen. De wereldbevolking stijgt gest aag, en zal dit in de toekomst blijven doen. Al deze monden zullen echte r moeten gevoed worden. De wetenschap zal dan ook een onafgebroken inspa nning moeten blijven leveren om de plantaardige en dierlijke productie t e optimaliseren. Een meer rationeel gebruik van schaarse natuurlijke bro nnen zoals energie en water vormen hierbij belangrijke elementen. De groei en ontwikkeling van alle levende organismen (waaronder mensen, dieren, planten en micro-organismen) worden, naast genetische factoren, ook beïnvloed door een complex geheel van micro-omgevingsfactoren. Een e fficiënte sturing ervan houdt twee voorwaarden in. Ten eerste dient er e en continue meting te zijn van de procesuitgang(en) of van één of meerde re variabelen die deze beïnvloeden. Ten tweede moet er een betrouwbare p redictie zijn (dynamisch model), die beschrijft hoe de procesuitgang(en) reageren op een verandering van de regelingang(en). Tot op heden werd voor biologische processen niet voldaan aan deze voorw aarden. Er wordt in sturingssystemen in de praktijk nog steeds geen cont inue meting van de biologische reactie (verder aangeduid met de term plantrespons of biorespons) van het levende organisme gebruikt, ho ewel het levende organisme in alle gevallen het belangrijkste procesonde rdeel is. In de tuinbouw bijvoorbeeld, wordt de continue biorespons van de planten op de variërende micro-omgeving niet opgevolgd noch gebruikt om bij te sturen. Het klimaat in de serre wordt nog steeds gestuurd op é én meetpunt van het klimaat per serrecompartiment, zonder op de plant ze lf te meten. Bovendien zal de biorespons maar correct interpreteerbaar z ijn wanneer de lokale micro-omgeving gekend is en deze laatste variee rt zelf ook in tijd en ruimte. Sinds de jaren zeventig is de speaking plant benadering een onderzo ekstopic. De basisidee hier is om de plantstatus permanent op te volgen en te sturen door gebruik te maken van korte-termijn respons op de omgev ing als terugkoppelingssignaal. Tot op vandaag heeft deze veelbelovende benadering echter geen succes gehad door ondermeer het gebrek aan kwanti tatieve gegevens van de micro-omgeving rondom de bladeren en planten. Bo vendien reageren alle organismen individueel verschillend, zodat een ada ptieve aanpak noodzakelijk is. Een goede meting en predictie van de resp ons van de plant op zijn veranderende micro-omgeving is zeer belangrijk om ongewenste omgevingsfactoren sneller te detecteren, nog voor het mens elijke oog dit kan. In dit onderzoek werd aangetoond dat 3-D gradiënten in luchttemperatuur en lichtintensiteit in een gewas niet te verwaarlozen zijn. Zowel in een kleine plantengroeikamer als in een semi-commerciële serre werden grote verschillen geregistreerd, afhankelijk van de lichtinstraling. De dynam iek van de in tijd en ruimte variërende verdeling van de luchttemperatuu r in dit niet-perfect gemengd fluïdum werd gemodelleerd, aan de hand van data uit dynamische stapexperimenten. De resultaten toonden dat een eerste orde model volstond om de dynamiek van dit complexe proces te bes chrijven (RT2 > 91,0 %). De grote ruimtelijke verschillen in luchttemperatuur resulteerden evenee ns in grote verschillen in bladtemperatuur, welke beïnvloed wordt doo r zijn micro-omgeving. Bij stapexperimenten in temperatuur en lichtinten siteit kwam een dynamisch eerste orde gedrag van de bladtemperatuur n aar voor in respons op deze beide individuele systeemingangen. De transf erfunctiemodellen beschreven de respons steeds voor minimaal 92,7 %. Een belangrijk probleem bij de modellering van complexe biologische proc essen is de complexiteit van de mathematische modellen. De bestaande mec hanistische modellen met biologische betekenis zijn zeer complex, te com plex voor efficiënte monitoring en sturing. De eenvoudige black box mo dellen daarentegen hebben geen biologische betekenis in de parameters ma ar tot op heden bestond er geen systematische methode om deze betekenis te definiëren. Hieraan wil de datagebaseerde mechanistische modellerings techniek (DBM) een antwoord bieden. De dynamische plantresponsie fotosynthese werd gemodelleerd aan de hand van de datagebaseerde mechanistische modelleringstechniek. In een eerste datagebaseerde fase wordt een mathematisch (black box) model met la ge complexiteit opgesteld aan de hand van technieken voor systeemidentif icatie. De modelorde, bepaald aan de hand van kwantitatieve criteria, ge eft het aantal relevante processen weer die zich in de plant voordoen en die dominant zijn om de dynamiek tijdens een veranderende lichtintensit eit te beschrijven. Om in een tweede fase, de mechanistische interpreta tie fase, fysiologisch en fysisch inzicht te brengen in de black box modelparameters, is in dit werk een methodologie ontwikkeld, om dit prob leem op een meer systematische manier aan te pakken. De methode houdt ee n meerstappenplan in, dat in hoofdzaak bestaat uit het ontbinden van de lage orde mathematische modellen in een combinatie van verschillende eer ste orde modellen, geconfigureerd in serie, parallel en/of terugkoppelin g, op een stabiele en (fysiologisch) realistische manier, waarna elk van de eerste orde modellen kan geïdentificeerd worden met een dominant fys iologisch (sub)proces. Als voorbeeld is de dynamische modellering uitgewerkt van de verandering van de netto CO2-assimilatie door het blad bij veranderingen in lichtin tensiteit. De modellering van de verandering van de CO2-assimilatie door het blad wanneer licht aangeschakeld wordt, (donker-licht inductieres pons) toonde een derde orde modelstructuur, en dus zijn drie dominante p rocessen betrokken, die bepalend zijn voor het globale CO2-fixatieproces . Deze processen werden, in vergelijking met bestaande literatuur, geïde ntificeerd als (1) de carboxylatie en (2) de oxygenatie (fotorespiratie) van ribulose-bisfosfaat (RuBP), beide gekatalyseerd door het enzym Rubi sco, en (3) de opening van de huidmondjes (zij limiteren de CO2 toevoer naar het blad). De respons van de CO2-assimilatie op een verandering van lage naar hoge lichtintensiteit werd best gemodelleerd door een eerste orde model en was ontbindbaar in een snelle en een trage respons, respec tievelijk geïdentificeerd als een onmiddellijke stijging van de carboxyl atie (gelimiteerd door de intercellulaire CO2-concentratie) en een gelei delijke opening van de huidmondjes (waardoor de CO2 toevoer steeg). De r espons van de CO2-assimilatie wanneer licht uitgeschakeld werd, werd gek arakteriseerd door een minimum en bleek een tweede orde modelstructuur t e hebben. Een snelle val van de RuBP regeneratie en de superpositie van een carboxylatie en oxygenatie, beide dalend door een krimpende RuBP voo rraad uit de laatste lichtperiode, waren de belangrijkste processen, die deze respons bepaalden. Samenvattend kan gesteld worden dat de datagebaseerde mechanistische mod elleringstechniek een geschikte aanpak is voor de ontwikkeling van eenvo udige en betekenisvolle dynamische modellen; welke de speaking plant, de fytomonitoring, tot een succes kunnen maken, onder de voorwaarde dat de micro-omgeving van de plant gekend is.status: Publishe
Níveis plasmáticos de neopterina e IL-10 como marcadores de depressão e alteração de personalidade associados ao traumatismo cranioencefálico grave
Dissertação (mestrado) - Universidade Federal de Santa Catarina, Centro de Ciências da Saúde, Programa de Pós-Graduação em Ciências Médicas, Florianópolis, 2015.Justificativa: Traumatismo cranioencefálico é um grave problema de saúde pública, devido sua alta incidência, mortalidade e morbidade. No Brasil, cerca de 341 casos por 100.000 habitantes são registrados anualmente. Aproximadamente 50% dos sobreviventes de TCE grave apresentam sequelas de longo prazo e o aumento do risco da depressão é bem estabelecido, podendo estar relacionado com o processo inflamatório no sistema nervoso central (SNC). Objetivos: Identificar a associação dos níveis de marcadores inflamatórios (NPT e IL-10) com a incidência de depressão e alteração de personalidade após TCE grave. Resultados: Indivíduos do sexo masculino constituíam 78,4% da amostra e a idade média das vítimas de TCE grave foi de 31 anos. Dentre as variáveis sócio-demográficas, psiquiátricas e de hospitalização analisadas, apenas níveis séricos elevados de IL-10 (p=0,03) e a razão entre citocinas pró e anti-inflamatórias (TNF-a/IL-10, p=0,01) estiveram independentemente associados ao aparecimento da depressão pós TCE. A incidência de alteração de personalidade foi de 24,3%. Não houve associação dos níveis séricos de neopterina (TCE agudo) com a gravidade do TCE, tempo de coleta ou com a taxa de mortalidade (p=0,82). Conclusões e implicações: Nossos resultados sugerem que o aumento sérico dos níveis de IL-10 podem ser usados como um biomarcador de mau prognóstico em pacientes vítimas de TCE grave tanto na fase aguda (mortalidade hospitalar) como na fase crônica (depressão) do TCE. Os mecanismos envolvidos nas associações observadas continuam desconhecidos e precisam ser investigados em mais estudos.Abstract : Justification: traumatic brain injury (TBI) is a serious public health problem due to its high incidence, mortality and morbitidy. In Brazil, the annual incidence of traumatic brain injury (TBI) is approximately 341 cases per 100,000 inhabitants. Approximately 50% of severe TBI survivors have long-term sequelae that impair their functionality and social reintegration. The cause of the incresead risk of depression after TBI is unclear but may be inflammatory-related with incresead brain sensitivity to secondary inflammatory challenges. Objectives: Identify the association of levels of inflammatory markers (NPT and IL-10) with the incidence of depression and personality disorders after severe TBI. Results: The sample was comprised primarily for male gender (78,4%) and the mean age of the victims was 31 years old. Among all the socio demographics, psychiatric and hospitalization variables, only the serum levels of IL-10 (p = 0.03) and the ratio between pro- and antiinflammatory cytokines (TNF-a / IL-10, p = 0.01) were independently associated with depression after TBI. The incidence of personality change was 24.3%. There was no association of serum neopterin (acute TBI) with the severity of TBI, time of collection of blood samples or the mortality rate (p = 0.82). Conclusions: our results suggests that enhanced levels o IL-10 are a biomarker of worse prognosis of severe TBI patients evaluated in the acute (hospital mortality) and chronic (depression) phases of TBI. The mechanism involved in the observed associations remain to be investigated
An ERP investigation of premotor sensory activity and response control in adults with Developmental Coordination Disorder.
Within the Developmental Coordination Disorder (DCD) literature the primary research focus has been directed towards children with DCD. Little has been investigated regarding the long term prognosis of these individuals with regards to the impact of the disorder in later life. Also, previous investigations and resulting suggestions of underlying aetiology have been based on behavioural data of poor performance with few studies examining the underlying biological considerations. Thus, the research within this thesis had two key aims. The first being to examine underlying processes associated with adaptive and goal directed movement in a sample of adults with DCD. The second aim was to provide biological evidence for the continued difficulties of adults with DCD.
Previous work in the area of cognitive psychology has identified distinct sensory and motor control functions as hallmarks of efficient and adaptive movement. This thesis explores the underlying sensory and motor control abilities of adults with DCD. There were two key aspects of this thesis with the first consisting of an investigation into the manner in which adults with DCD utilize sensory functions as a consequence of movement preparation. The secondary portion of this thesis focused on two key aspects of response modulation, the ability to effectively activate cortical regions underpinning effector response and response inhibition. Both aspects of the thesis drew methodological influences from the field of electroencephalography. This approach provided direct biological measurement of both sensory and response related activity.
The data obtained within this thesis provides evidence that adults with DCD do in fact demonstrate both atypical behavioural and biological functions during manual response activity. Chapter 4 highlighted key behavioural findings identifying that the DCD group demonstrates continued difficulty with accurate movement compared to typically developing peers. Chapters 5 and 6 focused on sensory activity as a consequence of movement preparation. The findings from these chapters suggest that adults with DCD present with maladaptive early sensory processing functions required for accurate movement output. Findings from the later chapters investigating response related activity suggest that adults with DCD experience difficulty with both measures of response activation and inhibition.
In summary, these findings suggest that adults with DCD experience an array of sensorimotor and response related difficulties vital to adaptive goal directed movement. Importantly, the findings presented within this thesis are the first to present direct biological based evidence for continued difficulties in a sample of adults with DCD. Conclusions are discussed in relation to previous research along with the possible influences these findings have in behaviour. The limitations of the current research and suggestions for future work are also considered
Fluoxetine restores spatial learning but not accelerated forgetting in mesial temporal lobe epilepsy
Learning and memory dysfunction is the most common neuropsychological effect of mesial temporal lobe epilepsy, and because the underlying neurobiology is poorly understood, there are no pharmacological strategies to help restore memory function in these patients. We have demonstrated impairments in the acquisition of an allocentric spatial task, in patients with unilateral hippocampal sclerosis. We also show that patients have accelerated forgetting of the learned spatial task and that this is associated with damage to the non-dominant hippocampal formation. We go on to show a very similar pattern of chronic allocentric learning and accelerated forgetting in a status epilepticus model of mesial temporal lobe epilepsy in rats, which is associated with reduced and abnormal hippocampal neurogenesis. Finally, we show that reversal of the neurogenic deficit using fluoxetine is associated with reversal of the learning deficit but not the accelerated forgetting, pointing to a possible dissociation in the underlying mechanisms, as well as a potential therapeutic strategy for improving hippocampal-dependent learning in patients with mesial temporal lobe epilepsy
