Did standard curve, calculated concentrations for BCL-2 ELISA.
Patient recruited - LP and blood collection, then aliquoted samples in PC2 lab.
Organised specimens for other labs (NMR and mass spec.) BCL-2 ELISA performed. Mass Spec Samples: Patient 1: 200 ul + (40 µL BCL2): From Box 1, A1 Patient 27: 200 ul + (40 µL BCL2) From Box 1, I8. Patient 41: 200 ul From Box 8, B1, B2. + (40 µL BCL2)
Patient 24: 200 ul + (40 µL BCL2) Patient 26: 200 ul Patient 35: 200 ul (I1, I2)
Patient 32: 50 ul Patient 34: 50 ul Patient 36: 50 ul Patient 45: 50 ul
Patient 31: 50 ul Patient 39: 50 ul Patient 42: 50 ul Patient 44: 50 ul
Completed lab induction to mass spectroscopy lab. Normal meetings.
--Mark Hill 09:34, 16 May 2009 (EST) Aims of the project
Aim: To investigate the pathophysiology of delirium and its association with dementia at a neuronal and patient level. Hypothesis: That delirium is caused by diffuse neuronal apoptosis, with a relationship between the severity of delirium, “frailty” of the neurons due to co-existing neurodegenerative disease and extent of neuronal death.
Delirium is a key issue in geriatric medicine and the most common problem affecting older hospitalised patients. It is associated with higher rates of dementia, functional impairment and placement in residential care. Different neurotransmitters and amino acid precursors may be affected in delirium. Previous studies have only examined one neurotransmitter system at a time, with little evidence regarding the type of delirium seen in older medical inpatients. This project will involve biochemical analysis of patient CSF samples and investigation of apoptotic pathways to determine the association between apoptosis of neurons and delirium and whether this is the major mechanism of neuronal loss in dementia.
Project Plan Student tasks over 32 weeks. Please note that students will be enrolled in extra Faculty courses at the same time as the ILP. For more information on structure of the ILP over the 32 week timeframe.
Phase 1 involves learning about the presentation, manifestations and pathophysiology of delirium, including its association with dementia. This involves wide reading on the topic and clinical work to appreciate the range of clinical presentations of delirium. It will involve a literature review and completion of courses to ensure safe lab work. The ILP is based in the Geriatric Medicine Unit at POWH and the Cell Biology Laboratory at UNSW.
Phase 2 involves a mixture of clinical and laboratory work. Investigation of patients with delirium will include neuropsychological assessment, venepuncture to collect blood and lumbar puncture for CSF. Students will learn how to manage specimens into -80 storage and ELISA assay techniques. They will conduct their own laboratory work on these and previously collected specimens. They will gain an understanding of interactions between delirium and dementia.
Phase 3 involves completion of experimental work and follow-up of previously enrolled participants. Students will write a report of their work with a view to publication.
This project will contribute to an improved understanding of the pathophysiology of delirium, which, for such a common and dangerous condition, has received little research. It has the potential to confirm that delirium is due to apoptosis and to identify delirium as the acute transient cause of previously unexplained cell death in dementia.
Students will gain an understanding of the pathophysiology of delirium, its diverse clinical presentations and interaction with dementia. They will learn about CSF biochemistry and how apoptotic pathways and neurotransmitters play a role in delirium via hands-on laboratory work.
Inouye, S.K. Delirium in older persons. N Engl J Med 2006; 354: 1157-65. McCusker J, Cole M, Dendukuri N, Belzile E, Primeau F. Delirium in older medical inpatients and subsequent cognitive and functional status: a prospective study. CMAJ 2001; 165: 575-583. Takuma K, Yan SS, Stern DM, Yamada K. Mitochondrial dysfunction, endoplasmic reticulum stress, and apoptosis in Alzheimer’s disease. J Pharmacol Sci 2005; 97: 312-316.