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1.
Can J Anaesth ; 70(9): 1504-1515, 2023 09.
Article in English | MEDLINE | ID: mdl-37523142

ABSTRACT

PURPOSE: Chronic pain is a common condition affecting almost one in five Canadians. One of the methods used to treat chronic pain is injection therapies. While they are considered relatively safe procedures, they do carry inherent risk that can result in adverse events. Our goal was to investigate these patient safety events to identify themes that could be used to shape practice guidelines and standards and improve patient safety. METHODS: We looked at closed civil legal actions and regulatory college complaints associated with injection therapies for chronic pain in the Canadian Medical Protection Association database from 2015 to 2019. Injury was defined as that arising from, or associated with, plans or actions taken during the provision of health care, rather than an underlying disease or injury. RESULTS: Of the 91 cases identified, the most common reported complications were neurologic-related symptoms, injury, and infection. Fifty-eight percent (53/91) of patients experienced health care-related harm that had a negative effect on their health or quality of life. Peer experts were critical of the clinical care provided in 74% (67/91) of the cases. Provider-related (60%, 40/67), team-related (75%, 50/67), and system-related factors (21%, 14/67) were identified as contributing factors in these cases. Common examples of provider-related factors were deficiencies in clinical decision-making (48%, 19/40), failure to follow established procedures (43%, 17/40), and situational awareness (38%, 15/40). Common examples of team-related factors were deficiencies in medical record keeping (80%, 40/50) and communication breakdowns (56%, 28/50). All system-related factors were related to inadequate office procedures. CONCLUSION: We recommend that clinicians conduct appropriate physical examinations, keep up-to-date with clinical standards, and ensure their documentation reflects their assessment, the patient's condition, and the treatment rationale.


RéSUMé: OBJECTIF: La douleur chronique est une affection courante qui touche près d'une personne sur cinq au Canada. Les traitements par injections constituent l'une des méthodes utilisées pour traiter la douleur chronique. Bien que ces thérapies soient considérées comme des interventions relativement sécuritaires, elles comportent des risques inhérents qui peuvent entraîner des événements indésirables. Notre objectif était d'examiner ces événements liés à la sécurité des patient·es afin de cerner les thèmes qui pourraient être utilisés pour façonner les lignes directrices et les normes de pratique et améliorer la sécurité des patient·es. MéTHODE: Nous avons examiné les poursuites civiles fermées et les plaintes aux ordres de réglementation associées aux traitements par injection pour la douleur chronique dans la base de données de l'Association canadienne de protection médicale entre 2015 et 2019. Était considérée comme blessure toute lésion découlant de ou associée à des plans mis en place ou des mesures prises pendant la prestation de soins de santé, plutôt que comme une maladie ou une blessure sous-jacente. RéSULTATS: Sur les 91 cas identifiés, les complications les plus fréquemment signalées étaient des symptômes, des blessures et des infections neurologiques. Cinquante-huit pour cent (53/91) des patient·es ont subi des préjudices liés aux soins de santé qui ont eu un effet négatif sur leur santé ou leur qualité de vie. Les expert·es ont critiqué les soins cliniques fournis dans 74 % (67/91) des cas. Les facteurs liés aux prestataires (60 %, 40/67), à l'équipe (75 %, 50/67) et au système (21 %, 14/67) ont été identifiés comme des facteurs contributifs dans ces cas. Les exemples courants de facteurs liés aux prestataires comportaient les lacunes dans la prise de décision clinique (48 %, 19/40), le non-respect des procédures établies (43 %, 17/40) et la conscience situationnelle (38 %, 15/40). Les lacunes dans la tenue des dossiers médicaux (80 %, 40/50) et les problèmes de communication (56 %, 28/50) comptaient parmi les exemples courants de facteurs liés à l'équipe. Tous les facteurs identifiés comme étant systémiques étaient liés à des procédures administratives inadéquates. CONCLUSION: Nous recommandons aux cliniciennes et cliniciens de réaliser des examens physiques appropriés, de se tenir au courant des normes cliniques et de s'assurer que leur documentation reflète leur évaluation, l'état du/de la patient·e et la justification du traitement.


Subject(s)
Chronic Pain , Humans , Chronic Pain/therapy , Pain Management , Quality of Life , Canada , Documentation
2.
Curr Oncol ; 29(11): 8207-8221, 2022 10 29.
Article in English | MEDLINE | ID: mdl-36354708

ABSTRACT

INTRODUCTION: Cinemeducation, the pedagogical use of films, has been used in a variety of clinical disciplines. To date, no studies have looked at the use of film depictions of cancer pain and its management in clinical education. We investigated how patients with cancer pain and their management are depicted in Hollywood films to determine whether there is content that would be amenable to use for cancer pain assessment and management education. METHODS: A qualitative content analysis was performed. Films that contained characters with or references to cancer pain were searched for using the International Movie Database, the Literature Arts Medicine Database, the History of Medicine and Medical Humanities Database, and Medicine on Screen. After review, 4 films were identified for review and analysis. RESULTS: Themes that emerged from the analysis concerned the films' depictions of characters with pain, their healthcare providers, the therapies used for pain management, and the setting in which pain management was provided. CONCLUSIONS: This study demonstrates that patients with cancer pain are depicted in a compassionate manner. Pain management focused on the use of opioids. The settings in which patients received pain management was depicted as not being amenable to providing holistic care. This variety of topics related to pain management covered in the films make them amenable to use in cinemeducation. This study therefore forms the basis for future work developing film-based cancer education modules.


Subject(s)
Cancer Pain , Neoplasms , Humans , Motion Pictures , Cancer Pain/drug therapy , Nuclear Family , Delivery of Health Care , Neoplasms/complications
3.
Can J Pain ; 6(1): 195-210, 2022.
Article in English | MEDLINE | ID: mdl-36324369

ABSTRACT

The watching of films is popular and accessible to broad segments of the population. The depiction of medical conditions in films has the potential to affect the public's perception of them and contribute to stereotypes and stigma. We investigated how patients with chronic pain and their management are depicted in feature films. Films that contained characters with or references to chronic pain were searched for using databases such as the International Movie Database. Themes that emerged from the content analysis revolved around the films' depictions of characters with pain, their health care providers, and therapies for pain management. Patients with chronic pain were depicted in various ways, including in manners that could elicit empathy from audiences or that might contribute to the development of negative stereotypes about them. The attitudes of health care professionals toward patients with chronic pain ranged from compassionate to dispassionate. Pain management was typically depicted as lacking in breadth or using multidisciplinary approaches with a focus on pharmacological management. The variety of topics related to chronic pain depicted in feature films lends to their use in medical education strategies to better inform health care professions trainees about chronic pain management.


Le visionnement de films est populaire et accessible à de larges segments de la population. La représentation des affections médicales dans les films est susceptible d'affecter la perception qu'en a le public et de contribuer aux stéréotypes et à la stigmatisation. Nous avons étudié comment les patients souffrant de douleur chronique et leur prise en charge sont représentés dans les longs métrages. Les films qui contenaient des personnages ou des références à la douleur chronique ont été recherchés à l'aide de bases de données telles que l'International Movie Database. Les thèmes qui sont ressortis de l'analyse du contenu tournaient autour des représentations des personnages souffrant de douleur, de leurs prestataires de soins de santé et des traitements pour la prise en charge de la douleur. Les patients souffrant de douleur chronique étaient représentés de diverses manières, y compris de manière à susciter l'empathie du public ou contribuer à l'apparition de stéréotypes négatifs à leur sujet. L'attitude des professionnels de la santé à l'égard des patients souffrant de douleur chronique allait de la compassion à la circonspection. La prise en charge de la douleur était généralement décrite comme manquant d'envergure ou utilisant des approches multidisciplinaires, tout en mettant l'accent sur la prise en charge pharmacologique. La variété des sujets liés à la douleur chronique présentés dans les longs métrages favorise leur utilisation dans les stratégies d'éducation médicale pour mieux informer les professionnels de la santé en formation sur la prise en charge de la douleur chronique.

4.
Can J Pain ; 6(1): 142-170, 2022.
Article in English | MEDLINE | ID: mdl-36092247

ABSTRACT

Background: Though chronic pain is widespread, affecting about one-fifth of the world's population, its impacts are disproportionately felt across the population according to socioeconomic determinants such as education and income. These factors also influence patients' access to treatment, including pharmacological pain management. Aim: A scoping review was undertaken to better understand the association of socioeconomic factors with physicians' pain management prescribing patterns for adults living with chronic pain. Methods: An electronic literature search was conducted using the EMBASE, CINAHL, SCOPUS, and Ovid MEDLINE databases and 31 retrieved articles deemed relevant for analyses were critically appraised. Results: The available evidence indicates that patients' lower socioeconomic status is associated with a greater likelihood of being prescribed opioids to manage their chronic pain and a decreased likelihood of receiving prescription medications to manage migraines, rheumatoid arthritis, and osteoarthritis. Conclusions: These results suggest that individuals with lower socioeconomic status do not receive equal prescription medicine opportunities to manage their chronic pain conditions. This is influenced by a variety of intersecting variables, including access to care, the potential unaffordability of certain therapies, patients' health literacy, and prescribing biases. Future research is needed to identify interventions to improve equity of access to therapies for patients with chronic pain living in lower socioeconomic situations as well as to explain the mechanism through which socioeconomic status affects chronic pain treatment choices by health care providers. Abbreviation: SES: socioeconomic status; RA: rheumatoid arthritis; IV: intravenous; SC: subcutaneous; bDMARDs: biological disease-modifying antirheumatic drugs; DMARDS; disease-modifying antirheumatic drugs; TNFi: tumour necrosis factor inhibitors; NSAIDs: non-steroidal anti-inflammatory drugs.


Contexte: Bien que la douleur chronique soit répandue, touchant environ un cinquième de la population mondiale, ses effets sont ressentis de manière disproportionnée au sein de la population en fonction de déterminants tels que l'éducation et le revenu. Ces facteurs influencent également l'accès des patients aux traitements, y compris la prise en charge pharmacologique de la douleur.Objectif: Un examen de la portée a été entrepris pour mieux comprendre l'association entre les facteurs socioéconomiques et les tendances manifestées par les médecins en matière d'ordonnances pour la prise en charge de la douleur chez les adultes vivant avec une douleur chronique.Méthodes: Une recherche documentaire électronique a été effectuée à l'aide des bases de données EMBASE, CINAHL, SCOPUS et Ovid MEDLINE. Par la suite, 31 articles récupérés qui avaient été jugés pertinents pour les analyses ont été soumis à une évaluation critique.Résultats: Les données disponibles indiquent que le statut socioéconomique inférieur des patients est associé à une plus grande probabilité de se voir prescrire des opioïdes pour la prise en charge de leur douleur chronique et à une diminution de la probabilité de recevoir des médicaments sur ordonnance pour prendre en charge les migraines, la polyarthrite rhumatoïde et l'ostéoarthrite.Conclusions: Ces résultats indiquent que les personnes ayant un statut socioéconomique inférieur ne bénéficient pas des mêmes possibilités de médicaments sur ordonnance pour prendre en charge leur douleur chronique. Cela est influencé par une variété de variables croisées, y compris l'accès aux soins, le fait que certains traitements soient potentiellement inabordables, la littératie de santé des patients et les préjugés en matière d'ordonnances. D'autres études sont nécessaires pour recenser les interventions visant à améliorer l'équité d'accès aux traitements pour les patients souffrant de douleur chronique vivant dans des situations socioéconomiques plus faibles, ainsi que pour expliquer le mécanisme par lequel le statut socioéconomique affecte les choix de traitement de la douleur chronique par les prestataires de soins de santé.

5.
J Obstet Gynaecol Can ; 44(7): 750-756, 2022 07.
Article in English | MEDLINE | ID: mdl-35202866

ABSTRACT

OBJECTIVE: To determine whether cannabis users have different pain scores after gynaecologic oncology surgery than non-cannabis users. METHODS: A retrospective chart review was completed for 654 patients who underwent gynaecologic oncology surgery during a 2-year period. The primary outcome was postoperative pain at 12 and 36 hours after surgery using an 11-point pain scale. Secondary outcomes included opioid consumption, length of hospital stay, opioid side effects, and sleep disturbance. RESULTS: Of all patients included in this study, 64 used cannabis and 590 did not. Propensity score matching and list-wise deletion identified 57 matched pairs. Pain scores were significantly higher at 12 hours (P < 0.001) and 36 hours (P =0.002) after surgery in cannabis users (median pain scores 6 [IQR 5-7]) and 5 [IQR 4-7], respectively) than non-users (median pain scores 4 [IQR 3-6] and 4 ([IQR 2-5], respectively). Median opioid consumption was significantly higher at 12 hours (P = 0.039) and 36 hours (P = 0.044) after surgery in cannabis users (oral morphine equivalent [OME] 20 [IQR 10-40] mg and OME 40 [IQR 10-100] mg, respectively) than non-users (OME 10 [IQR 5-20] mg and OME 30 mg [IQR 7.5-50] mg, respectively]. Sleep disturbance was significantly higher in cannabis users (odds ratio 3.31; P = 0.009). CONCLUSIONS: After gynaecologic oncology surgery, patients who used cannabis preoperatively had higher postoperative pain scores, higher opioid use, and more sleep disturbance than non-users. This suggests that preoperative cannabis use is a risk factor for postoperative pain.


Subject(s)
Cannabis , Genital Neoplasms, Female , Analgesics/therapeutic use , Analgesics, Opioid/therapeutic use , Female , Genital Neoplasms, Female/surgery , Humans , Pain, Postoperative/drug therapy , Retrospective Studies
7.
J Neurosurg Pediatr ; : 1-5, 2019 Sep 06.
Article in English | MEDLINE | ID: mdl-31491753

ABSTRACT

Transorbital penetration accounts for one-quarter of the penetrating head injuries (PHIs) in adults and half of those in children. Injuries that traverse (with complete penetration of) the brainstem are often fatal, with survivors rarely seen in clinical practice. Here, the authors describe the case of a 16-year-old male who suffered and recovered from an accidental transorbital PHI traversing the brainstem-the first case of complete neurological recovery following such injury. Neuroimaging captured the trajectory of the initial injury. A delayed-onset carotid cavernous fistula and the subsequent development of internal carotid artery pseudoaneurysms were managed by endovascular embolization.The authors also review the relevant literature. Sixteen cases of imaging-confirmed PHI traversing the brainstem have been reported, 14 involving the pons and 12 penetrating via the transorbital route. Management and outcome of PHI are informed by object velocity, material, entry point, trajectory, relationship to neurovascular structures, and the presence of a retained foreign body. Trauma resuscitation is followed by a careful neurological examination and appropriate neuroimaging. Ophthalmological examination is performed if transorbital penetration is suspected, as injuries may be occult; the potential for neurovascular complications highlights the value of angiography. The featured case shows that complete recovery is possible following injury that traverses the brainstem.

8.
Curr Stem Cell Res Ther ; 6(3): 229-54, 2011 Sep.
Article in English | MEDLINE | ID: mdl-21476982

ABSTRACT

Tissue-specific human neural precursor cells (hNPCs) can be isolated from various regions of the developing or adult central nervous system and may serve as a viable source of cells in cell replacement therapies for the treatment of neurodegenerative disorders. However, in order for cell replacement strategies to become a routine therapeutic option for the treatment of neurodegenerative disorders, hNPCs should be generated under standardized and controlled conditions. Studies over the last two decades have focused on developing cell growth media and cell handling protocols for expansion and differentiation of hNPCs in culture. Key studies have reported the development of serum-free growth media and large-scale computer-controlled suspension bioreactors that can support high cell proliferation rates (doubling times < 3 days), multipotentiality, and potential neurogenic differentiation (more than 60% neurons). Moreover, bioengineering studies have focused on controlling culture conditions in suspension bioreactors including inoculation, hydrodynamics of culture, oxygen and nutrients transfer to the cells, monitoring in situ physiological parameters using process control techniques, and expansion for extended periods of time. In addition, in vitro and in vivo characterization of hNPCs have been performed, providing information on stem/progenitor cell characteristics, cell surface analysis, and appropriate type of cells to use in transplantation studies.


Subject(s)
Batch Cell Culture Techniques/methods , Bioreactors , Clinical Trials as Topic/methods , Neural Stem Cells/cytology , Animals , Antigens, Surface/metabolism , Batch Cell Culture Techniques/instrumentation , Cell Differentiation , Clinical Trials as Topic/instrumentation , Culture Media , Drug Delivery Systems , Humans , Neural Stem Cells/metabolism , Neural Stem Cells/physiology , Neural Stem Cells/transplantation , Neurodegenerative Diseases/therapy , Time-Lapse Imaging
9.
Biotechnol Prog ; 27(3): 776-87, 2011.
Article in English | MEDLINE | ID: mdl-21485037

ABSTRACT

Understanding initial cell growth, interactions associated with the process of expansion of human neural precursor cells (hNPCs), and cellular events pre- and postdifferentiation are important for developing bioprocessing protocols to reproducibly generate multipotent cells that can be used in basic research or the treatment of neurodegenerative disorders. Herein, we report the in vitro responses of telencephalon hNPCs grown in a serum-free growth medium using time-lapse live imaging as well as cell-surface marker, aggregate size, and immunocytochemical analyses. Time-lapse analysis of hNPC initial expansion indicated that cell-surface attachment in stationary culture and the frequency of cell-cell interaction in suspension conditions are important for subsequent aggregate formation and hNPC growth. In the absence of cell-surface attachment in low-attachment stationary culture, large aggregates of cells were formed and expansion was adversely affected. The majority of the telencephalon hNPCs expressed CD29, CD90, and CD44 (cell surface markers involved in cell-ECM and cell-cell interactions to regulate biological functions such as proliferation), suggesting that cell-surface attachment and cell-cell interactions play a significant role in the subsequent formation of cell aggregates and the expansion of hNPCs. Before differentiation, about 90% of the cells stained positive for nestin and expressed two neural precursor cells surface markers (CD133 and CD24). Upon withdrawal of growth cytokines, hNPCs first underwent cell division and then differentiated preferentially towards a neuronal rather than a glial phenotype. This study provides key information regarding human NPC behavior under different culture conditions and favorable culture conditions that are important in establishing reproducible hNPC expansion protocols.


Subject(s)
Cell Communication , Cell Proliferation , Neural Stem Cells/cytology , Antigens, CD/analysis , Bioengineering , Cell Culture Techniques/methods , Cell Differentiation/drug effects , Culture Media, Serum-Free , Cytokines/drug effects , Humans , Telencephalon/cytology
10.
J Neurotrauma ; 27(10): 1805-18, 2010 Oct.
Article in English | MEDLINE | ID: mdl-20698759

ABSTRACT

Autonomic dysreflexia consistently develops in patients and in rats after severe upper thoracic spinal cord injury (SCI) as a result of exaggerated spinal sympathetic excitation. In this study we induced episodic hypertension in rats after varying degrees of SCI severity to investigate the contribution of serotonergic bulbospinal axons to the development of autonomic dysreflexia after SCI. Female Wistar rats (250-300 g) were used in all experiments in the following groups: (1) uninjured, (2) clip compression at T4 of 20, 35, or 50 g, (3) spinal cord transection at T4, and (4) intrathecal 5,7-dihydroxytryptamine creatinine sulfate (5,7-DHT). Immunohistochemistry for choline acetyl transferase and serotonin (5-HT) was performed on T8-T12 spinal segments to identify sympathetic preganglionic neurons, and to assess 5-HT-containing axons in the intermediolateral cell column (IMLC), respectively. Testing for autonomic dysreflexia was conducted by measuring mean arterial pressure (MAP) at rest and after colon distension-induced hypertension. We observed that the magnitude of the pressor response seen after colon distension correlated with SCI severity and density of 5-HT-immunoreactive axons in the IMLC. Intrathecal administration of the 5-HT(2A) agonist dimethoxy-4-iodamphetamine increased resting MAP and blocked colon distension-induced hypertension, whereas the 5-HT(2A) antagonist ketanserin decreased resting MAP and was permissive to the colon distension-induced pressor response in SCI rats. These results suggest that the SCI-induced loss of serotonergic inputs into the spinal cord IMLC is proportional to the pathogenesis of autonomic dysreflexia and hypotension seen after SCI. We thus conclude that sparing of serotonergic axons beyond a critical threshold preserves cardiovascular regulation and prevents the development of autonomic dysreflexia.


Subject(s)
Autonomic Dysreflexia/etiology , Autonomic Dysreflexia/physiopathology , Axons/metabolism , Serotonin/metabolism , Spinal Cord Injuries/complications , Analysis of Variance , Animals , Autonomic Dysreflexia/metabolism , Axons/drug effects , Blood Pressure/drug effects , Blood Pressure/physiology , Choline O-Acetyltransferase/metabolism , Female , Heart Rate/drug effects , Heart Rate/physiology , Immunohistochemistry , Indophenol/analogs & derivatives , Indophenol/pharmacology , Injections, Spinal , Ketanserin/pharmacology , Motor Activity/physiology , Rats , Rats, Wistar , Serotonin Antagonists/pharmacology , Serotonin Receptor Agonists/pharmacology , Spinal Cord Injuries/metabolism , Spinal Cord Injuries/physiopathology
11.
Childs Nerv Syst ; 26(4): 491-502, 2010 Apr.
Article in English | MEDLINE | ID: mdl-20174925

ABSTRACT

INTRODUCTION: The localization of tumors and epileptogenic foci within the somatosensory or language cortex of the brain of a child poses unique neurosurgical challenges. In the past, lesions in these regions were not treated aggressively for fear of inducing neurological deficits. As a result, while function may have been preserved, the underlying disease may not have been optimally treated, and repeat neurosurgical procedures were frequently required. Today, with the advent of preoperative brain mapping, image guidance or neuronavigation, and intraoperative monitoring, peri-Rolandic and language cortex lesions can be approached directly and definitively with a high degree of confidence that neurosurgical function will be maintained. METHODS AND RESULTS: The preoperative brain maps can now be achieved with magnetic resonance imaging (MRI), functional MRI, magnetoencephalography, and diffusion tensor imaging. Image guidance systems have improved significantly and include the use of the intraoperative MRI. Somatosensory, motor, and brainstem auditory-evoked potentials are used as standard neuromonitoring techniques in many centers around the world. Added to this now is the use of continuous train-of-five monitoring of the integrity of the corticospinal tract while operating in the peri-Rolandic region. CONCLUSION: We are in an era where continued advancements can be expected in mapping additional pathways such as visual, memory, and hearing pathways. With these new advances, neurosurgeons can expect to significantly improve their surgical outcomes further.


Subject(s)
Monitoring, Intraoperative/methods , Neurosurgical Procedures/methods , Brain/physiopathology , Brain/surgery , Brain Neoplasms/complications , Brain Neoplasms/physiopathology , Brain Neoplasms/surgery , Child , Diagnostic Imaging/methods , Female , Humans , Neoplasms, Neuroepithelial/complications , Neoplasms, Neuroepithelial/physiopathology , Neoplasms, Neuroepithelial/surgery , Seizures/etiology , Seizures/physiopathology , Seizures/surgery
12.
Biotechnol Bioeng ; 105(4): 823-33, 2010 Mar 01.
Article in English | MEDLINE | ID: mdl-19882735

ABSTRACT

Human neural precursor cells (hNPCs), harvested from somatic tissue and grown in vitro, may serve as a source of cells for cell replacement strategies aimed at treating neurodegenerative disorders such as Parkinson's disease (PD), Huntington's disease (HD), and intractable spinal cord pain. A crucial element in a robust clinical production method for hNPCs is a serum-free growth medium that can support the rapid expansion of cells while retaining their multipotency. Here, we report the development of a cell growth medium (PPRF-h2) for the expansion of hNPCs, achieving an overall cell-fold expansion of 10(13) over a period of 140 days in stationary culture which is significantly greater than other literature results. More importantly, hNPC expansion could be scaled-up from stationary culture to suspension bioreactors using this medium. Serial subculturing of the cells in suspension bioreactors resulted in an overall cell-fold expansion of 7.8 x 10(13) after 140 days. These expanded cells maintained their multipotency including the capacity to generate large numbers of neurons (about 60%). In view of our previous studies regarding successful transplantation of the bioreactor-expanded hNPCs in animal models of neurological disorders, these results have demonstrated that PPRF-h2 (containing dehydroepiandrosterone, basic fibroblast growth factor and human leukemia inhibitory factor) can successfully facilitate the production of large quantities of hNPCs with potential to be used in the treatment of neurodegenerative disorders.


Subject(s)
Bioreactors , Cell Culture Techniques/methods , Neurodegenerative Diseases/therapy , Neurogenesis , Neurons/cytology , Cell- and Tissue-Based Therapy , Cells, Cultured , Humans
13.
Expert Rev Neurother ; 8(7): 1125-39, 2008 Jul.
Article in English | MEDLINE | ID: mdl-18590482

ABSTRACT

With an increase in the aging population, the incidence of Parkinson's disease (PD), a disabling neurodegenerative disorder mainly affecting motor function, will inevitably present a challenge to an already overburdened healthcare system. Current medical and surgical therapies offer symptomatic relief but do not provide a cure. Experimental studies suggest that GDNF has the ability to protect degenerating dopamine neurons in PD as well as promote regeneration of the nigrostriatal dopamine system. However, clinical trials of GDNF infusion to date remain inconclusive. This review will examine the experimental and clinical evidence of GDNF use in PD with particular focus on its potential as an effective therapy in the treatment of PD.


Subject(s)
Cell- and Tissue-Based Therapy/methods , Genetic Therapy/methods , Glial Cell Line-Derived Neurotrophic Factor/therapeutic use , Parkinson Disease/therapy , Animals , Clinical Trials as Topic , Dopamine/metabolism , Glial Cell Line-Derived Neurotrophic Factor/metabolism , Humans
15.
Nat Med ; 14(5): 507-9, 2008 May.
Article in English | MEDLINE | ID: mdl-18391961

ABSTRACT

Postmortem analysis of five subjects with Parkinson's disease 9-14 years after transplantation of fetal midbrain cell suspensions revealed surviving grafts that included dopamine and serotonin neurons without pathology. These findings are important for the understanding of the etiopathogenesis of midbrain dopamine neuron degeneration and future use of cell replacement therapies.


Subject(s)
Brain Tissue Transplantation/pathology , Fetal Tissue Transplantation/pathology , Neurons/pathology , Parkinson Disease/therapy , Brain Tissue Transplantation/methods , Fetal Tissue Transplantation/methods , Humans , Immunohistochemistry , Male , Middle Aged , Parkinson Disease/diagnostic imaging , Positron-Emission Tomography , Treatment Outcome , Tyrosine 3-Monooxygenase
16.
Biotechnol Prog ; 24(4): 859-70, 2008.
Article in English | MEDLINE | ID: mdl-18380486

ABSTRACT

The transplantation of in vitro expanded human neural precursor cells (hNPCs) represents a potential new treatment alternative for individuals suffering from incurable neurodegenerative disorders such as Parkinson's disease (PD) and Huntington's disease (HD). However, in order for cell restorative therapy to have widespread therapeutic significance, it will be necessary to generate unlimited quantities of clinical grade hNPCs in a standardized method. We report here that we have developed a serum-free medium and scale-up protocols that allow for the generation of clinical quantities of human telencephalon-derived hNPCs in 500-mL computer-controlled suspension bioreactors. The average hNPC aggregate diameter in the bioreactors was maintained below a target value of 500 microm by controlling the liquid shear field. The human cells, which were inoculated at 10(5) cells/mL, exhibited a doubling time of 84 h, underwent a 36-fold expansion over the course of 18 days, and maintained an average viability of over 90%. The bioreactor-derived hNPCs retained their nestin expression following expansion and were able to differentiate into glial and neuronal phenotypes under defined conditions. It has also been demonstrated that these hNPCs differentiated to a GABAergic phenotype that has recently been shown to be able to restore functional behavior in rat models of HD and neuropathic pain (Mukhida, K. et al. Stem Cells 2007; DOI 10.1634/stemcells.2007-0326). This study demonstrates that clinical quantities of hNPCs can be successfully and reproducibly generated under standardized conditions in computer-controlled suspension bioreactors.


Subject(s)
Bioreactors , Cell Culture Techniques/methods , Neurodegenerative Diseases/therapy , Neurons/physiology , Stem Cells/physiology , Cell Aggregation , Cell Differentiation , Cells, Cultured , Humans , Neurons/cytology , Oxygen/metabolism , Stem Cells/cytology
17.
Neurosurg Focus ; 24(3-4): E8, 2008.
Article in English | MEDLINE | ID: mdl-18341411

ABSTRACT

OBJECT: Fetal tissue transplantation for Parkinson disease (PD) has demonstrated promising results in experimental and clinical studies. However, the widespread clinical application of this therapeutic approach is limited by a lack of fetal tissue. Human neural precursor cells (HNPCs) are attractive candidates for transplantation because of their long-term proliferation activity. Furthermore, these cells can be reproducibly expanded in a standardized fashion in suspension bioreactors. In this study the authors sought to determine whether the survival, differentiation, and migration of HNPCs after transplantation depended on the region of precursor cell origin, intracerebral site of transplantation, and duration of their expansion. METHODS: Human neural precursor cells were isolated from the telencephalon, brainstem, ventral mesencephalon, and spinal cord of human fetuses 8-10 weeks of gestational age, and their differentiation potential characterized in vitro. After expansion in suspension bioreactors, the HNPCs were transplanted into the striatum and substantia nigra of parkinsonian rats. Histological analyses were performed 7 weeks posttransplantation. RESULTS: The HNPCs isolated from various regions of the neuraxis demonstrated diverse propensities to differentiate into astrocytes and neurons and could all successfully expand under standardized conditions in suspension bioreactors. At 7 weeks posttransplantation, survival and migration were significantly greater for HNPCs obtained from the more rostral brain regions. The HNPCs differentiated predominantly into astrocytes after transplantation into the striatum or substantia nigra regions, and thus no behavioral improvement was observed. CONCLUSIONS: Understanding the regional differences in HNPC properties is prerequisite to their application for PD cell restoration strategies.


Subject(s)
Bioreactors , Cell Differentiation/physiology , Cell Movement/physiology , Embryonic Stem Cells/physiology , Neurons/physiology , Parkinson Disease/pathology , Amphetamine/pharmacology , Animals , Behavior, Animal/drug effects , Cell Survival , Central Nervous System/cytology , Central Nervous System/embryology , Central Nervous System Stimulants , Disease Models, Animal , Female , Fetus , Humans , Parkinson Disease/etiology , Parkinson Disease/physiopathology , Parkinson Disease/therapy , Rats , Rats, Wistar , Stem Cell Transplantation/methods
18.
Neuropsychiatr Dis Treat ; 4(6): 1111-28, 2008 Dec.
Article in English | MEDLINE | ID: mdl-19337454

ABSTRACT

Tourette's syndrome (TS) is a neurological disorder characterized by motor and vocal tics that typically begin in childhood and often are accompanied by psychiatric comorbidities. Symptoms of TS may be socially disabling and cause secondary medical complications. Pharmacological therapies remain the mainstay of symptom management. For the subset of patients in whom TS symptoms are medically recalcitrant and do not dissipate by adulthood, neurosurgery may offer an alternative treatment strategy. Greater understanding of the neuroanatomic and pathophysiologic basis of TS has facilitated the development of surgical procedures that aim to ameliorate TS symptoms by lesions or deep brain stimulation of cerebral structures. Herein, the rationale for the surgical management of TS is discussed and neurosurgical experiences since the 1960s are reviewed. The necessity for neurosurgical strategies to be performed with appropriate ethical considerations is highlighted.

19.
Can J Surg ; 50(6): 485-9, 2007 Dec.
Article in English | MEDLINE | ID: mdl-18053379

ABSTRACT

The origins of neurosurgical services in Atlantic Canada are tied to the individual efforts of William D. Stevenson. Born in Hamilton, Ontario, Stevenson completed his senior matriculation in Dunnville, Ontario, before studying medicine at the University of Toronto. He completed the Gallie surgical course in Toronto and then spent 1 year training with Edward Archibald at McGill University. After working for 2 years with the Canadian Mobile Neurosurgical Unit in Europe during the Second World War, Stevenson undertook formal neurosurgical training with Kenneth G. McKenzie, Canada's first neurosurgeon. Stevenson was thereafter recruited to Halifax to start the neurosurgical service at the Victoria General Hospital in January 1948, and he remained head of the division for the next 26 years. His pioneering work laid the foundations for the establishment of a major academic neurosurgical service at Dalhousie University and was crucial for the establishment of neurosurgery in Atlantic Canada. After his retirement, Stevenson moved back to Ontario and began his second career, transferring his passion for neurosurgery to oil painting. His legacy to neurosurgery in Atlantic Canada will be remembered in perpetuity with the annual Neurosurgery Resident Research Award at Dalhousie University, established and named in his honour. This paper focuses on Stevenson's life and work in neurosurgery as Atlantic Canada's first neurosurgeon.


Subject(s)
Neurosurgery/history , Canada , History, 20th Century , Humans
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