41 results on '"Kilpatrick, Trevor"'
Search Results
2. Association Between Cognitive Trajectories and Disability Progression in Patients With Relapsing-Remitting Multiple Sclerosis.
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Merlo, Daniel, Stankovich, Jim, Bai, Claire, Kalincik, Tomas, Zhu, Chao, Gresle, Melissa, Lechner-Scott, Jeannette, Kilpatrick, Trevor, Barnett, Michael, Taylor, Bruce, Darby, David, Butzkueven, Helmut, and Van der Walt, Anneke
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- 2021
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3. Clinical impact of whole-genome sequencing in patients with early-onset dementia
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Huq, Aamira J, Thompson, Bryony, Bennett, Mark F, Bournazos, Adam, Bommireddipalli, Shobhana, Gorelik, Alexandra, Schultz, Joshua, Sexton, Adrienne, Purvis, Rebecca, West, Kirsty, Cotter, Megan, Valente, Giulia, Hughes, Andrew, Riaz, Moeen, Walsh, Maie, Farrand, Sarah, Loi, Samantha M, Kilpatrick, Trevor, Brodtmann, Amy, Darby, David, Eratne, Dhamidhu, Walterfang, Mark, Delatycki, Martin Bruce, Storey, Elsdon, Fahey, Michael, Cooper, Sandra, Lacaze, Paul, Masters, Colin L, Velakoulis, Dennis, Bahlo, Melanie, James, Paul A, and Winship, Ingrid
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BackgroundIn the clinical setting, identification of the genetic cause in patients with early-onset dementia (EOD) is challenging due to multiple types of genetic tests required to arrive at a diagnosis. Whole-genome sequencing (WGS) has the potential to serve as a single diagnostic platform, due to its superior ability to detect common, rare and structural genetic variation.MethodsWGS analysis was performed in 50 patients with EOD. Point mutations, small insertions/deletions, as well as structural variants (SVs) and short tandem repeats (STRs), were analysed. An Alzheimer’s disease (AD)-related polygenic risk score (PRS) was calculated in patients with AD.ResultsClinical genetic diagnosis was achieved in 7 of 50 (14%) of the patients, with a further 8 patients (16%) found to have established risk factors which may have contributed to their EOD. Two pathogenic variants were identified through SV analysis. No expanded STRs were found in this study cohort, but a blinded analysis with a positive control identified a C9orf72expansion accurately. Approximately 37% (7 of 19) of patients with AD had a PRS equivalent to >90th percentile risk.DiscussionWGS acts as a single genetic test to identify different types of clinically relevant genetic variations in patients with EOD. WGS, if used as a first-line clinical diagnostic test, has the potential to increase the diagnostic yield and reduce time to diagnosis for EOD.
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- 2022
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4. Association Between Cognitive Trajectories and Disability Progression in Patients With Relapsing-Remitting Multiple Sclerosis
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Merlo, Daniel, Stankovich, Jim, Bai, Claire, Kalincik, Tomas, Zhu, Chao, Gresle, Melissa, Lechner-Scott, Jeannette, Kilpatrick, Trevor, Barnett, Michael, Taylor, Bruce, Darby, David, Butzkueven, Helmut, and Van der Walt, Anneke
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- 2021
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5. Identification and Characterisation of cis-Regulatory Elements Upstream of the Human Receptor Tyrosine Kinase Gene MERTK
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Walsh, Alexander D., Johnson, Laura J., Harvey, Alexandra J., Kilpatrick, Trevor J., and Binder, Michele D.
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MERTKencodes a receptor tyrosine kinase that regulates immune homeostasis via phagocytosis of apoptotic cells and cytokine-mediated immunosuppression. MERTKis highly expressed in the central nervous system (CNS), specifically in myeloid derived innate immune cells and its dysregulation is implicated in CNS pathologies including the autoimmune disease multiple sclerosis (MS). While the cell types and tissues that express MERTKhave been well described, the genetic elements that define the gene’s promoter and regulate specific transcription domains remain unknown. The primary objective of this study was to define and characterise the human MERTKpromoter region. We cloned and characterized the 5’ upstream region of MERTKto identify cis-acting DNA elements that promote gene transcription in luciferase reporter assays. In addition, promoter regions were tested for sensitivity to the anti-inflammatory glucocorticoid dexamethasone. This study identified identified both proximal and distal-acting DNA elements that promote transcription. The strongest promoter activity was identified in an ∼850 bp region situated 3 kb upstream of the MERTKtranscription start site. Serial deletions of this putative enhancer revealed that the entire region is essential for expression activity. Using in silicoanalysis, we identified several candidate transcription factor binding sites. Despite a well-established upregulation of MERTKin response to anti-inflammatory glucocorticoids, no DNA region within the 5 kb putative promoter was found to directly respond to dexamethasone treatment. Elucidating the genetic mechanisms that regulate MERTKexpression gives insights into gene regulation during homeostasis and disease, providing potential targets for therapeutic modulation of MERTKtranscription.
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- 2021
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6. Case Report: Confirmation by Metagenomic Sequencing of Visceral Leishmaniasis in an Immunosuppressed Returned Traveler.
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Williams, Eloise, Isles, Nicole S., Seemann, Torsten, Kilpatrick, Trevor, Grigg, Andrew, Leroi, Marcel, Howden, Benjamin P., and Kwong, Jason C.
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- 2020
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7. Achievements and obstacles of remyelinating therapies in multiple sclerosis
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Stangel, Martin, Kuhlmann, Tanja, Matthews, Paul M., and Kilpatrick, Trevor J.
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Remyelination in the CNS is the natural process of damage repair in demyelinating diseases such as multiple sclerosis (MS). However, remyelination becomes inadequate in many people with MS, which results in axonal degeneration and clinical disability. Enhancement of remyelination is a logical therapeutic goal; nevertheless, all currently licensed therapies for MS are immunomodulatory and do not support remyelination directly. Several molecular pathways have been identified as potential therapeutic targets to induce remyelination, and some of these have now been assessed in proof-of-concept clinical trials. However, trial design faces several obstacles: optimal clinical or paraclinical outcome measures to assess remyelination remain ill-defined, and identification of the ideal timing of therapy is also a crucial issue. In addition, realistic expectations are needed concerning the probable benefits of such therapies. Nevertheless, approaches that enhance remyelination are likely to be protective for axons and so could prevent long-term neurodegeneration. Future MS treatment paradigms, therefore, are likely to comprise a combinatorial approach that involves both immunomodulatory and regenerative treatments.
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- 2017
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8. A Functional and Neuropathological Testing Paradigm Reveals New Disability-Based Parameters and Histological Features for P0180-190-Induced Experimental Autoimmune Neuritis in C57BL/6 Mice.
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Gonsalvez, David G, De Silva, Mithraka, Wood, Rhiannon J, Giuffrida, Lauren, Kilpatrick, Trevor J, Murray, Simon S, and Xiao, Junhua
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We assessed novel disability-based parameters and neuropathological features of the P0180-190 peptide-induced model of experimental autoimmune neuritis (EAN) in C57BL/6 mice. We show that functional assessments such as running capacity provide a more sensitive method for detecting alterations in disease severity than a classical clinical scoring paradigm. We performed detailed ultrastructural analysis and show for the first time that tomaculous neuropathy is a neuropathological feature of this disease model. In addition, we demonstrate that ultrastructural assessments of myelin pathology are sufficiently sensitive to detect significant differences in both mean G-ratio and mean axon diameter between mice with EAN induced with different doses of pertussis toxin. In summary, we have established a comprehensive assessment paradigm for discriminating variations in disease severity and the extent of myelin pathology in this model. Our findings indicate that this model is a powerful tool to study the pathogenesis of human peripheral demyelinating neuropathies and that this assessment paradigm could be used to determine the efficacy of potential therapies that aim to promote myelin repair and protect against nerve damage in autoimmune neuritides.
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- 2017
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9. High-efficiency pharmacogenetic ablation of oligodendrocyte progenitor cells in the adult mouse CNS
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Xing, Yao Lulu, Poh, Jasmine, Chuang, Bernard H.A., Moradi, Kaveh, Mitew, Stanislaw, Richardson, William D., Kilpatrick, Trevor J., Osanai, Yasuyuki, and Merson, Tobias D.
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Approaches to investigate adult oligodendrocyte progenitor cells (OPCs) by targeted cell ablation in the rodent CNS have limitations in the extent and duration of OPC depletion. We have developed a pharmacogenetic approach for conditional OPC ablation, eliminating >98% of OPCs throughout the brain. By combining recombinase-based transgenic and viral strategies for targeting OPCs and ventricular-subventricular zone (V-SVZ)-derived neural precursor cells (NPCs), we found that new PDGFRA-expressing cells born in the V-SVZ repopulated the OPC-deficient brain starting 12 days after OPC ablation. Our data reveal that OPC depletion induces V-SVZ-derived NPCs to generate vast numbers of PDGFRA+NG2+cells with the capacity to proliferate and migrate extensively throughout the dorsal anterior forebrain. Further application of this approach to ablate OPCs will advance knowledge of the function of both OPCs and oligodendrogenic NPCs in health and disease.
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- 2023
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10. A new era in the treatment of multiple sclerosis.
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Broadley, Simon A., Barnett, Michael H., Boggild, Mike, Brew, Bruce J., Butzkueven, Helmut, Heard, Robert, Hodgkinson, Suzanne, Kermode, Allan G., Lechner-Scott, Jeannette, Macdonell, Richard AL, Marriott, Mark, Mason, Deborah F., Parratt, John, Reddel, Stephen W., Shaw, Cameron P., Slee, Mark, Spies, Judith M., Taylor, Bruce V., Carroll, William M., and Kilpatrick, Trevor J.
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The article discusses a study which reviewed several Phase III clinical trials and Cochrane reviews on treatments for multiple sclerosis (MS) across New Zealand and Australia. Topics covered include analysis of levels of efficacies in various therapies, relapsing-remitting MS and risks for progressive multifocal leukoencephalopathy (PML) with natalizumab. Findings showed association of MS therapies with lymphopenia, development of idiopathic thrombocytopenic purpura (ITP) and thyroid disease.
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- 2015
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11. Therapeutic approaches to disease modifying therapy for multiple sclerosis in adults: An Australian and New Zealand perspective Part 2 New and emerging therapies and their efficacy.
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Broadley, Simon A., Barnett, Michael H., Boggild, Mike, Brew, Bruce J., Butzkueven, Helmut, Heard, Robert, Hodgkinson, Suzanne, Kermode, Allan G., Lechner-Scott, Jeannette, Macdonell, Richard A.L., Marriott, Mark, Mason, Deborah F., Parratt, John, Reddel, Stephen W., Shaw, Cameron P., Slee, Mark, Spies, Judith, Taylor, Bruce V., Carroll, William M., and Kilpatrick, Trevor J.
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In Part 2 of this three part review of multiple sclerosis (MS) treatment with a particular focus on the Australian and New Zealand perspective, we review the newer therapies that have recently become available and emerging therapies that have now completed phase III clinical trial programs. We go on to compare the relative efficacies of these newer and emerging therapies alongside the existing therapies. The effectiveness of β-interferon in the treatment of different stages and the different disease courses of MS is critically reviewed with the conclusion that the absolute level of response in term of annualised relapse rates (where relapses occur) and MRI activity are similar, but are disappointing in terms of sustained disability progression for progressive forms of the disease. Finally we review the controversial area of combination therapy for MS. Whilst it remains the case that we have no cure or means of preventing MS, we do have a range of effective therapies that when used appropriately and early in the disease course can have a significant impact on short term and longer term outcomes. [ABSTRACT FROM AUTHOR]
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- 2014
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12. Therapeutic approaches to disease modifying therapy for multiple sclerosis in adults: An Australian and New Zealand perspective Part 3 Treatment practicalities and recommendations.
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Broadley, Simon A., Barnett, Michael H., Boggild, Mike, Brew, Bruce J., Butzkueven, Helmut, Heard, Robert, Hodgkinson, Suzanne, Kermode, Allan G., Lechner-Scott, Jeannette, Macdonell, Richard A.L., Marriott, Mark, Mason, Deborah F., Parratt, John, Reddel, Stephen W., Shaw, Cameron P., Slee, Mark, Spies, Judith, Taylor, Bruce V., Carroll, William M., and Kilpatrick, Trevor J.
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In this third and final part of our review of multiple sclerosis (MS) treatment we look at the practical day-to-day management issues that are likely to influence individual treatment decisions. Whilst efficacy is clearly of considerable importance, tolerability and the potential for adverse effects often play a significant role in informing individual patient decisions. Here we review the issues surrounding switching between therapies, and the evidence to assist guiding the choice of therapy to change to and when to change. We review the current level of evidence with regards to the management of women in their child-bearing years with regards to recommendations about treatment during pregnancy and whilst breast feeding. We provide a summary of recommended pre- and post-treatment monitoring for the available therapies and review the evidence with regards to the value of testing for antibodies which are known to be neutralising for some therapies. We review the occurrence of adverse events, both the more common and troublesome effects and those that are less common but have potentially much more serious outcomes. Ways of mitigating these risks and managing the more troublesome adverse effects are also reviewed. Finally, we make specific recommendations with regards to the treatment of MS. It is an exciting time in the world of MS neurology and the prospects for further advances in coming years are high. [ABSTRACT FROM AUTHOR]
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- 2014
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13. Therapeutic approaches to disease modifying therapy for multiple sclerosis in adults: An Australian and New Zealand perspective Part 1 Historical and established therapies.
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Broadley, Simon A., Barnett, Michael H., Boggild, Mike, Brew, Bruce J., Butzkueven, Helmut, Heard, Robert, Hodgkinson, Suzanne, Kermode, Allan G., Lechner-Scott, Jeannette, Macdonell, Richard A.L., Marriott, Mark, Mason, Deborah F., Parratt, John, Reddel, Stephen W., Shaw, Cameron P., Slee, Mark, Spies, Judith, Taylor, Bruce V., Carroll, William M., and Kilpatrick, Trevor J.
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Multiple sclerosis (MS) is a potentially life-changing immune mediated disease of the central nervous system. Until recently, treatment has been largely confined to acute treatment of relapses, symptomatic therapies and rehabilitation. Through persistent efforts of dedicated physicians and scientists around the globe for 160 years, a number of therapies that have an impact on the long term outcome of the disease have emerged over the past 20 years. In this three part series we review the practicalities, benefits and potential hazards of each of the currently available and emerging treatment options for MS. We pay particular attention to ways of abrogating the risks of these therapies and provide advice on the most appropriate indications for using individual therapies. In Part 1 we review the history of the development of MS therapies and its connection with the underlying immunobiology of the disease. The established therapies for MS are reviewed in detail and their current availability and indications in Australia and New Zealand are summarised. We examine the evidence to support their use in the treatment of MS. [ABSTRACT FROM AUTHOR]
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- 2014
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14. Impact of telehealth on health care in a multiple sclerosis outpatient clinic during the COVID-19 pandemic.
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Li, Vivien, Roos, Izanne, Monif, Mastura, Malpas, Charles, Roberts, Stefanie, Marriott, Mark, Buzzard, Katherine, Nguyen, Ai-Lan, Seery, Nabil, Taylor, Lisa, Kalincik, Tomas, and Kilpatrick, Trevor
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• Patient satisfaction with telehealth was high with video consultations preferred. • Clinicians strongly preferred in-person visits which allow physical examination. • Telehealth-based EDSS was feasible but may under-estimate lower EDSS. • Treatment inertia may affect management decisions during telehealth consultations. The coronavirus disease 2019 (COVID-19) pandemic has precipitated expansion of telemedicine in outpatient management of chronic diseases including multiple sclerosis (MS). Studies conducted pre-pandemic, when telehealth was an alternative to in-person consultations, represent a different setting to current practice. The aim of this study was to assess the impact of telehealth on MS outpatient care in a tertiary metropolitan hospital in Melbourne, Australia during the COVID-19 pandemic. From March-December 2020, patients and clinicians in the MS outpatient clinic were surveyed regarding their attitudes towards telehealth. Scores on the Expanded Disability Status Scale (EDSS) from telehealth and face-to-face appointments during the study period were compared to scores from face-to-face consultations before and after this period. Medical records were reviewed to compare management decisions made during telehealth versus face-to-face consultations. Diagnoses and treatment of MS relapses were compared to 2019. Telehealth was used in 73% of outpatient appointments. Patient satisfaction was generally high. Patients and clinicians preferred face-to-face consultations but were willing to use telehealth longer term. Overall, there were no significant delays in identifying patients experiencing disability worsening via telehealth, but EDSS increase was recorded in more face-to-face than telehealth appointments particularly for those with lower baseline disability. Disease-modifying therapy commencement rates were similar, but symptomatic therapy initiation and investigation requests occurred more frequently in face-to-face visits. Comparable numbers of MS relapses were diagnosed and treated with corticosteroids in 2019 and 2020. Patient satisfaction with telehealth was high, but both clinicians and patients preferred in-person appointments. Telehealth implementation did not lead to high rates of undetected disability worsening or undiagnosed acute relapses, but telehealth-based EDSS assessment may underestimate lower scores. Treatment inertia may affect some management decisions during telehealth consultations. Telehealth will likely play a role in outpatient settings beyond the COVID-19 pandemic with further studies on its long-term impact on clinical outcomes required. [ABSTRACT FROM AUTHOR]
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- 2022
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15. Subjective versus objective performance in people with multiple sclerosis using the MSReactor computerised cognitive tests.
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Merlo, Daniel, Kalincik, Tomas, Zhu, Chao, Gresle, Melissa, Lechner-Scott, Jeannette, Kilpatrick, Trevor, Barnett, Michael, Taylor, Bruce, Buzzard, Katherine, Darby, David, Butzkueven, Helmut, and van der Walt, Anneke
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Perceived cognitive impairment in MS is associated with adverse changes in employment capacity, sexual function, and aspects of daily living. Studies have shown relationships between perceived cognitive impairment and objective neuropsychological functioning and mood. Subjective cognitive performance in people with MS has not previously been compared to their objective performance on a computerised cognitive battery. All participants completed at least 6-monthly serial testing on the MSReactor computerised cognitive testing platform consisting of 3 reaction time tasks. These measure psychomotor processing speed (simple reaction time), attention (choice reaction time) and working memory (One back task). In addition, we collected subjective cognitive performance and patient reported outcomes of depression, anxiety and quality of life. The strength and direction of the relationships between subjective and objective performance on the cognitive tasks were examined using Kendalls rank coefficient at year 1 and year 2. We calculated partial correlation estimates where subjective performance was also associated with patient reported outcomes. Subjective overall performance correlated weakly with the working memory task (Tau -0.10; (95% confidence interval (CI) -0.19, -0.01). Subjective performance also correlated weakly with depression but not anxiety or quality of life. Subjective reaction speed correlated weakly with psychomotor processing speed (Tau -0.10; CI -0.19, -0.01); and subjective accuracy correlated weakly with the attention (Tau 0.12; CI 0.03, 0.21) and working memory (Tau 0.15; CI 0.05, 0.24) tasks, respectively. Participants' perceived performance on the MSReactor tests correlated only weakly with objective changes. Depression was associated with subjective cognitive performance reports. These results suggest that a person with MS' perception of their cognitive performance is only weakly associated with cognitive changes detected using MSReactor. [ABSTRACT FROM AUTHOR]
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- 2022
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16. Nanodiamonds with silicon vacancy defects for nontoxic photostable fluorescent labeling of neural precursor cells.
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Merson, Tobias D., Castelletto, Stefania, Aharonovich, Igor, Turbic, Alisa, Kilpatrick, Trevor J., and Turnle, Ann M.
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- 2013
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17. Associations between Silicone Skin Cast Score, Cumulative Sun Exposure, and Other Factors in the Ausimmune Study: A Multicenter Australian Study.
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Lucas, Robyn M., Ponsonby, Anne-Louise, Dear, Keith, Taylor, Bruce V., Dwyer, Terence, McMichael, Anthony J., Valery, Patricia, van der Mei, Ingrid, Williams, David, Pender, Michael P., Chapman, Caron, Coulthard, Alan, and Kilpatrick, Trevor
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The article focuses on a study associating silicone skin casts score, cumulative sun exposure, and other factors to the degree of skin damage conducted at the four areas of Eastern Australian. It notes that the determinants of skin damage can be measured by silicone cast at the back of the hand, environmental factors and age. It also says that sun exposure behaviors and phenotypes are important factors in developing skin damage not just ambient ultraviolet radiation (UVR).
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- 2009
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18. Subjective versus objective performance in people with multiple sclerosis using the MSReactor computerised cognitive tests.
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Merlo, Daniel, Kalincik, Tomas, Zhu, Chao, Gresle, Melissa, Lechner-Scott, Jeannette, Kilpatrick, Trevor, Barnett, Michael, Taylor, Bruce, Buzzard, Katherine, Darby, David, Butzkueven, Helmut, and van der Walt, Anneke
- Abstract
Perceived cognitive impairment in MS is associated with adverse changes in employment capacity, sexual function, and aspects of daily living. Studies have shown relationships between perceived cognitive impairment and objective neuropsychological functioning and mood. Subjective cognitive performance in people with MS has not previously been compared to their objective performance on a computerised cognitive battery.
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- 2022
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19. Nanodiamonds with silicon vacancy defects for nontoxic photostable fluorescent labeling of neural precursor cells
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Merson, Tobias D., Castelletto, Stefania, Aharonovich, Igor, Turbic, Alisa, Kilpatrick, Trevor J., and Turnley, Ann M.
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Nanodiamonds (NDs) containing silicon vacancy (SiV) defects were evaluated as a potential biomarker for the labeling and fluorescent imaging of neural precursor cells (NPCs). SiV-containing NDs were synthesized using chemical vapor deposition and silicon ion implantation. Spectrally, SiV-containing NDs exhibited extremely stable fluorescence and narrow bandwidth emission with an excellent signal to noise ratio exceeding that of NDs containing nitrogen-vacancy centers. NPCs labeled with NDs exhibited normal cell viability and proliferative properties consistent with biocompatibility. We conclude that SiV-containing NDs are a promising biomedical research tool for cellular labeling and optical imaging in stem cell research.
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- 2013
20. Antisaccade performance in patients with multiple sclerosis
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Fielding, Joanne, Kilpatrick, Trevor, Millist, Lynette, and White, Owen
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Commonly used measures of disability in patients with Multiple sclerosis (MS) inadequately reflect disease severity and progression. Further, cognitive deficits experienced by up to 70% of patients, are poorly represented by these measures. Saccadic eye movements may provide a powerful tool for the analysis of cognitive changes in MS, providing a surrogate measure of performance that extends more conventional measures. The cognitive control of eye movements has not previously been investigated in patients with MS. We studied antisaccade (AS) performance in 25 patients with MS and compared the results with 25 age matched healthy controls, to evaluate the resolution of response conflict between volitional and automatic processes. Experimental measures were also correlated with a battery of neuropsychological tests evaluating attention, working memory and executive processes, the most commonly reported cognitive deficits in MS. Compared to controls, patients with MS generated significantly more prosaccade errors, and AS latencies were prolonged and more variable. Error rates correlated significantly with scores on the commonly used PASAT. MS patients also exhibited poor spatial accuracy, with mean absolute error significantly larger and more variable than control subjects. The sensitivity of this task in dissociating function in MS, as well as clear correlation with a key measure of cognition, suggests that eye movements, may provide a surrogate measure of cognitive function in MS, with the potential to sensitively assess disease severity and progression.
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- 2009
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21. Impact of telehealth on health care in a multiple sclerosis outpatient clinic during the COVID-19 pandemic
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Li, Vivien, Roos, Izanne, Monif, Mastura, Malpas, Charles, Roberts, Stefanie, Marriott, Mark, Buzzard, Katherine, Nguyen, Ai-Lan, Seery, Nabil, Taylor, Lisa, Kalincik, Tomas, and Kilpatrick, Trevor
- Abstract
•Patient satisfaction with telehealth was high with video consultations preferred.•Clinicians strongly preferred in-person visits which allow physical examination.•Telehealth-based EDSS was feasible but may under-estimate lower EDSS.•Treatment inertia may affect management decisions during telehealth consultations.
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- 2022
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22. Multiple sclerosis disability profile and quality of life in an Australian community cohort
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Khan, Fary, McPhail, Tracey, Brand, Caroline, Turner-Stokes, Lynne, and Kilpatrick, Trevor
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The objective of this study was to determine the experience of disability and reported symptoms in multiple sclerosis in an Australian community sample, comparing the perceptions of patients, carers and treating doctors, and to examine effects on quality of life, carer stress and utilization of health services. The study design used a prospective cross sectional community survey. The participants were persons with a confirmed diagnosis of multiple sclerosis, with quantified neurological, mobility and cognitive deficits, from a tertiary hospital database (n101), who lived at home, and their carers and doctors. The study method used demographic, diagnostic and disease severity data extracted from the database. Structured interviews conducted at home included (1) open questionnaires for participant, carer and general practitioner, prioritizing symptomsproblems affecting daily living; and (2) standardized assessments for patient quality of life, caregiver strain and perceived burden of care. The mean age was 49 years (range 28–64). Those more severely affected had a significantly reduced quality of life and increased carer burden than those with milder disability, but discordance between patients, carers and doctors was noted in their perception of problems and symptom experience. Rates of depression (67) and work-related problems were high, but vocational support was rarely provided. Forty persons used interferon, of whom 20 had secondary progressive multiple sclerosis; 39 reported difficulty in accessing rehabilitation services and only 10 were referred to medical rehabilitation units. In conclusion, the rates of disability and symptom experience were similar to other series; however, access and utilization of appropriate rehabilitation and support services appears to be lacking. There were higher reported rates of depression and poor quality of life. Opportunities may possibly exist to re-deploy resources to develop vocational support, counselling and rehabilitation.
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- 2006
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23. Neuroglial responses to CNS injury: prospects for novel therapeutics
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Kilpatrick, Trevor J, Butzkueven, Helmut, Emery, Ben, Marriott, Mark, Taylor, Bruce V, and Tubridy, Niall
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Immune-mediated therapies can reduce the relapse rate in multiple sclerosis. However, there is no clear-cut evidence that any of these therapies substantially alter the long-term outcome for patients with progressive multiple sclerosis. The neurological disability that all too frequently accompanies multiple sclerosis is ultimately due to injury to target cells, principally oligodendroglia, within the nervous system. Recent data suggest that activation of leukemia inhibitory factor-receptor signaling is an important component of a neurobiological response that serves to limit the extent of immune-mediated injury. Therefore, inactivation of this pathway could provide a novel approach to the treatment of demyelinating disease.
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- 2004
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24. Prospects for stem cell transplantation in multiple sclerosis
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Kilpatrick, Trevor J., Butzkueven, Helmut, and Grigg, Andrew
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- 2002
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25. Chopper, a New Death Domain of the p75 Neurotrophin Receptor That Mediates Rapid Neuronal Cell Death*
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Coulson, Elizabeth J., Reid, Kate, Baca, Manuel, Shipham, Kylie A., Hulett, Sarah M., Kilpatrick, Trevor J., and Bartlett, Perry F.
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The cytoplasmic juxtamembrane region of the p75 neurotrophin receptor (p75NTR) has been found to be necessary and sufficient to initiate neural cell death. The region was named “Chopper” to distinguish it from CD95-like death domains. A 29-amino acid peptide corresponding to the Chopper region induced caspase- and calpain-mediated death in a variety of neural and non-neural cell types and was not inhibited by signaling through Trk (unlike killing by full-length p75NTR). Chopper triggered cell death only when bound to the plasma membrane by a lipid anchor, whereas non-anchored Chopper acted in a dominant-negative manner, blocking p75NTR-mediated death both in vitroand in vivo. Removal of the ectodomain of p75NTRincreased the potency of Chopper activity, suggesting that it regulates the association of Chopper with downstream signaling proteins.
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- 2000
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26. Evaluating the perspective of patients with MS and related conditions on their DMT in relation to the COVID-19 pandemic in one MS centre in Australia.
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Seery, Nabil, Li, Vivien, Nguyen, Ai-Lan, Roos, Izanne, Buzzard, Katherine A, Atvars, Roberts, Taylor, Nicola, Tunnell, Kelsey, Carey, John, Dwyer, Chris, Taylor, Hasini Fernandoa Lisa, Baker, Josephine, Marriott, Mark P, Kilpatrick, Trevor J, Kalincik, Tomas, and Monif, Mastura
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• Covid-19 pandemic can have implications for MS and neuroimmunology patients and potentially their adherence to disease modifying therapies (DMTs). • A large proportion of patients receiving DMT's for their MS expressed some degree of concern regarding the COVID-19 pandemic and their therapy in one MS centre in Australia. • The level of concern in most patients was at most mild however. • Patients ascribed similar concern to the risk of a relapse of their disease compared to the risk of contracting COVID-19, perhaps underscoring a willingness to continue their DMT despite the pandemic. Objective: Patients with Multiple Sclerosis (MS) and on disease modifying therapies (DMTs) that can be immunosuppressive or immunomodulatory form a special group where risk of continuation of DMT needs to be taken into account with risk of contracting Covid-19. This concept can pose a degree of anxiety for patients as well as neurologists. We aimed to evaluate patient perspectives regarding the use of Natalizumab and anti-CD20 therapies (Rituximab and Ocrelizumab) in the context of the COVID-19 pandemic. Methods: cross-sectional study conducted via voluntary survey filled in by patients with MS and related disorders receiving their infusional treatment in one MS centre in Australia, exploring their concerns regarding their therapy, their therapy and COVID-19, precautions undertaken in response to the pandemic, and factors impacting their decision-making. Results: 170 patients completed the survey. Of patients on Natalizumab, the majority had either no or mild concern regarding their DMT and COVID-19, and of patients on B-cell depleting therapies, again, the majority had no or mild concern, though a slightly higher proportion had a moderate level of concern. Asked to delineate their concerns, an increased risk of contracting COVID-19 was more commonly conveyed than MS-specific factors or poor outcomes pertaining to COVID-19 if contracted, by patients in both groups. Conversely, being invited to specifically consider the possibility of contracting COVID-19 or experience a relapse of MS, almost half of the cohort rated both of equal of concern. More than half of the cohort were self-isolating more stringently than general government advice and government-related resources followed by information provided by patient's neurologist where the commonest means of information to guide decision making. Conclusions: Whilst a large proportion of patients had some concern regarding the impact of their DMT on COVID-19, whether on their risk of contracting COVID-19 or a theoretical risk for more severe disease, the overall level of concern in most cases was at most mild. Patients on B-cell depleting therapies were more inclined to express a higher level of concern. A similar concern was ascribed to a risk of a relapse or worsening MS symptoms compared to the risk of contracting COVID-19. Such attitudes may underscore a willingness of patients to continue their DMT where benefits outweigh risks during future phases of the COVID-19 pandemic. [ABSTRACT FROM AUTHOR]
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- 2020
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27. The MSReactor computerized cognitive battery correlates with the processing speed test in relapsing-remitting multiple sclerosis.
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Yam, Charmaine, Merlo, Daniel, Stankovich, Jim, Darby, David, Gresle, Melissa, Kalincik, Tomas, Kilpatrick, Trevor J., Lechner-Scott, Jeanette, Taylor, Bruce, Barnett, Michael, Butzkueven, Helmut, and van der Walt, Anneke
- Abstract
• The MSReactor battery could monitor for cognitive change in the clinic setting. • MSReactor battery correlates moderately with the Processing Speed Test. • The test-retest reliability was good for both tests over 6 months. • Depression and anxiety have minimal effect on MSReactor scores. • Manual dexterity has no effect on MSReactor and Processing Speed test scores. Monitoring and screening of cognitive function in the ambulatory setting requires simple, brief cognitive tests that are reproducible. MSReactor (MSR) is a web-based platform that screens psychomotor (processing) speed, attention and working memory using a game-like interface. The Processing Speed Test (PST) is a validated computerized version of the Symbol Digit Modalities test (SDMT) and component of the Multiple Sclerosis Performance Test (MSPT). To determine the baseline and 6-month predictive correlations between the MSReactor computerised cognitive battery and the PST. Prospectively enrolled relapsing-remitting multiple sclerosis (RRMS) patients completed the MSR and the PST during 6-monthly clinic visits. Pearson's product-moment coefficients with partial correlation adjustment were calculated between the PST and MSR reaction times for Simple reaction test (SRT), Choice reaction test (CRT) and One- back test (OBK). 379 RRMS patients from six tertiary MS centres in Australia were enrolled. The mean age was 40.4 years (SD 10.3) and median Expanded Disability Status Scale (EDSS) score was 1.5 (IQR 1.0 – 2.0). Most (66%) were on high efficacy disease-modifying treatment. Baseline PST scores correlated with the MSR reaction times: SRT (R =-0.40), CRT (R = -0.44) and OBK (R = -0.47), p <0.05. There was a moderate correlation between the first visit MSR and 6-month PST test for SRT (R = -0.37, p <0.001), CRT (R =-0.44, p < 0.001) and OBK (R = -0.43, p < 0.001) speed. MSR-measured psychomotor speed, attention and working memory at baseline moderately correlates with baseline and 6-month PST; suggesting overlapping cognitive processes are being tested. Six-month test-retest reliability was acceptable for both tests. [ABSTRACT FROM AUTHOR]
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- 2020
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28. Cerebrospinal Fluid Biochemistry in the Diagnosis of Multiple Sclerosis
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Ratnaike, Sujiva, Kilpatrick, Trevor, Tress, Brian, Davis, Stephen, Kilpatrick, Christine, Byron, Keith, and Deam, David
- Abstract
The Poser criteria for diagnosing multiple sclerosis (MS) includes clinical, paraclinical and laboratory information.1We studied the influence of cerebrospinal fluid (CSF) biochemistry results on the categorisation of patients with suspected MS.A retrospective study was made of 138 patients who had CSF samples sent over a 1 year period to the laboratory for examination for oligoclonal bands. Using the Poser criteria, 23 patients were diagnosed as having definite MS and one patient as probable MS. Cerebrospinal fluid biochemistry upgraded the categorisation from probable to definite MS in 16 of these 24 patients (66%).In this study, we found oligoclonal bands to be more sensitive in the diagnosis of MS (96%) than either the concentration of IgG in the CSF (43·5%) or the IgG expressed as a percentage of the total protein in the CSF (71%). We conclude that CSF biochemistry is a valuable investigation in the evaluation of patients with suspected MS.
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- 1990
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29. Neuroimmunology of demyelinating disease
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Bartlett, Perry F. and Kilpatrick, Trevor J.
- Abstract
The immunopathogenesis of multiple sclerosis appears to be dependent on the interaction between major histocompatibility cpmplex molecules, T-cell receptors, and peptide antigens. The mechanisms regulating this ‘tripartite’ system and their relevance to immune-mediated experimental and human demyelination and potential treatment strategies are reviewed.
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- 1991
30. Evaluating the perspective of patients with MS and related conditions on their DMT in relation to the COVID-19 pandemic in one MS centre in Australia
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Seery, Nabil, Li, Vivien, Nguyen, Ai-Lan, Roos, Izanne, Buzzard, Katherine A, Atvars, Roberts, Taylor, Nicola, Tunnell, Kelsey, Carey, John, Dwyer, Chris, Taylor, Hasini Fernandoa Lisa, Baker, Josephine, Marriott, Mark P, Kilpatrick, Trevor J, Kalincik, Tomas, and Monif, Mastura
- Abstract
•Covid-19 pandemic can have implications for MS and neuroimmunology patients and potentially their adherence to disease modifying therapies (DMTs).•A large proportion of patients receiving DMT's for their MS expressed some degree of concern regarding the COVID-19 pandemic and their therapy in one MS centre in Australia.•The level of concern in most patients was at most mild however.•Patients ascribed similar concern to the risk of a relapse of their disease compared to the risk of contracting COVID-19, perhaps underscoring a willingness to continue their DMT despite the pandemic.
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- 2020
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31. The MSReactor computerized cognitive battery correlates with the processing speed test in relapsing-remitting multiple sclerosis
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Yam, Charmaine, Merlo, Daniel, Stankovich, Jim, Darby, David, Gresle, Melissa, Kalincik, Tomas, Kilpatrick, Trevor J., Lechner-Scott, Jeanette, Taylor, Bruce, Barnett, Michael, Butzkueven, Helmut, and van der Walt, Anneke
- Abstract
•The MSReactor battery could monitor for cognitive change in the clinic setting.•MSReactor battery correlates moderately with the Processing Speed Test.•The test-retest reliability was good for both tests over 6 months.•Depression and anxiety have minimal effect on MSReactor scores.•Manual dexterity has no effect on MSReactor and Processing Speed test scores.
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- 2020
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32. Visceral leishmaniasis in a returned traveller on fingolimod therapy
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Williams, Eloise, Kilpatrick, Trevor, Grigg, Andrew, Leroi, Marcel, and Kwong, Jason C.
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- 2020
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33. Measurement of intracellular cytokines in MS patients treated with β-interferon and association of a β-interferon induced exacerbation with increased expression of γ-interferon by monocytes
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Toh, Ling and Kilpatrick, Trevor J.
- Abstract
The effects that immunomodulatory agents such as β-Interferon (IFN-β) exert upon cytokine production in autoimmune disease such as multiple sclerosis remain incompletely understood. The recent development of techniques to directly assess cytokine production within peripheral blood leucocytes promises to advance this field. β-Interferon treatment occasionally causes short-lived exacerbations of neurological dysfunction, often associated with systemic flu-like symptoms. Whereas these side effects usually occur and remit within the first few months of therapy, we have identifi ed several patients who have developed symptoms many months after the onset of treatment. To begin to investigate the cause of these late onset exacerbations, we assessed the intracellular cytokine profiles of two patients, one stable on IFN-β treatment and another experiencing side effects. The latter patient exhibited an increase in the percentage of monocytes that expressed g-Interferon after IFN-β administration, whereas no such modulation was seen in the patient without side effects.
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- 2001
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34. Immunosuppressive therapy is valuable in aggressive Multiple Sclerosis
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Kilpatrick, Trevor J. and Butzkueven, Helmut
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- 2000
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35. 134 Cladribine: a multicentre long-term efficacy biomarker australian study (CLOBAS)
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Lechner-Scott, Jeannette, Maltby, Vicky, Lyndon, Amanda, Monif, Mastura, Kilpatrick, Trevor, Butzkueven, Helmut, Taylor, Bruce, McCombe, Pamela, Hodgkinson, Suzanne, Fabis-Pedrini, Marzena, Kermode, Allan, Barnett, Michael, and Kalincik, Tomas
- Abstract
IntroductionCladribine tablets (marketed as Mavenclad®) is a new oral therapy, which has recently been listed on the pharmaceuticals benefit scheme (PBS) in Australia for treatment of relapsing MS. The current dosing schedule is for 2 courses given a year apart, which has been shown to be effective for treatment of MS up to 4 years in 75% of patients (based on annualised relapse rate). However, re-initiation of therapy after year 4 has not been studied.MethodsThis will be a multicentre, 6-year, phase IV, low interventional trial. Subjects considered for treatment with cladribine will receive an initial treatment course in year 1 and a continuing treatment course in year 2. After year 3, patients will have the option for re-dosing, if clinically indicated or to switch to another disease modifying therapy. Throughout the duration of the study we will assess blood based biomarkers including lymphocyte subsets, serum neurofilament light chain, DNA methylation and RNA analysis as well as MRI findings (brain volume/lesion load) and cognitive performance.ResultsThis study has been approved by the Hunter New England Local Health District Human Research Ethics Committee. The study is due to commence on March 14th.ConclusionsThis will be the first long-term efficacy trial of cladribine which offers re-initiation of therapy after the initial two courses. We expect this study will be an indication if any of the assessed biomarkers can be used to predict treatment efficacy or the need for re-initiation of Cladribine in MS patients.
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- 2019
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36. Paraclinical Correlates of Visual Acuity Loss in Multiple Sclerosis.
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Marriott, Mark, Kolbe, Scott C, Butzkueven, Helmut, Kilpatrick, Trevor J, and Egan, Gary F
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- 2009
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37. 89. Modulation of regulatory and cytotoxic T cell expression signature in first demyelinating events and early multiple sclerosis.
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Skibina, Olga G., Perreau, Victoria M., Hu, Yifang, Binder, Michele, Judith, Judith, Butzkueven, Helmut, Smyth, Gordon, and Kilpatrick, Trevor
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- 2010
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38. 29. Probing neuron-glial interactions for therapeutic benefit.
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Kilpatrick, Trevor
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- 2010
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39. Protracted form of Encephalitis with Good Outcome
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Frasca, Joseph, Burns, Richard J, and Kilpatrick, Trevor J
- Abstract
Objective: To present four patients seen over a five‐year period who developed severe protracted encephalitic illnesses but whose outcomes were favourable. Clinical features: Of the four patients, aged 18, 22, 34 and 19, three presented with acute psychosis, and all had a prolonged clinical course requiring intensive care management. One patient had residual generalised seizures and the other three recovered fully. No infective or toxic agent could be identified but viral encephalitis was considered most likely. Outcome: Despite the protracted courses, the outcomes were favourable. This is in contrast to the generally poor outcomes in encephalitis caused by established infective agents such as herpes simplex type 1. Conclusions: When the aetiology and hence the natural history of the encephalitis is unknown, long‐term intensive support is appropriate.
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- 1993
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40. Acute median nerve compression by haemorrhage from acute myelomonocytic leukaemia
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Kilpatrick, Trevor, Leyden, Michael, Sullivan, John, Lawler, Gary, and Grossman, Howard
- Abstract
A 61‐year‐old male receiving treatment for acute myelomonocytic leukaemia (AMML) developed weakness and sensory loss in the thumb, index and middle finger and half of the ring finger of the left hand as a result of a spontaneous haemorrhage into the carpal tunnel and forearm, an unusual cause of median nerve compression. These findings were confirmed by CT scanning and post‐mortem examination. This is the first report of spontaneous haemorrhage occurring in a patient with AMML.
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- 1985
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41. Schwann Cell Apoptosis in the Postnatal Axotomized Sciatic Nerve Is Mediated Via NGF through the Low-Affinity Neurotrophin Receptor
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PETRATOS, STEVEN, BUTZKUEVEN, HELMUT, SHIPHAM, KYLIE, COOPER, HELEN, BUCCI, TAMARA, REID, KATE, LOPES, ELIZABETH, EMERY, BEN, CHEEMA, SURINDAR S., and KILPATRICK, TREVOR J.
- Abstract
Schwann cell death is a developmentally regulated phenomenon and is also induced after peripheral nerve axotomy in neonatal rodents. In this study, we explored whether ligand-induced activation of the low-affinity neurotrophin receptor (p75NTR) is responsible for inducing Schwann cell death in vivo. Administration of exogenous nerve growth factor (NGF) to the axotomized nerve site in wild-type animals resulted in a 2.6-fold increase in Schwann cell apoptosis in the distal nerve stumps compared to axotomy alone. No increase in apoptosis, above baseline levels, was seen in p75NTR-mutant mice either with or without NGF. When anti-NGF antibodies were administered to the site of the peripheral nerve lesion in wild-type mice there was a reduction in the percentage of Schwann cell apoptosis to levels seen in both the quiescent state and in the axotomized nerves of the p75NTR-mutant mice. These results demonstrate that apoptosis of Schwann cells in axotomized peripheral nerve is mediated predominantly through p75NTR signaling and initiated via endogenously produced NGF.
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- 2003
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