The Goodpasture's epitope (GP) has recently been localized to the last 36 AA of the non-collagenous (NCl) domain of the alpha 3 chain of type IV collagen [alpha 3(IV)]. Since alpha 3(IV) induces glomerulonephritis (GN) in rats and rabbits, the purpose of the present study was to determine if the GP epitope itself could induce GN. We immunized rats with synthetic peptides of GP epitope, 36-mer, alone or as protein conjugates. Rats immunized with bovine GBM served as positive controls. Peptide immunized rats developed high titer antibodies to peptides, but only unconjugated 36-mer induced antibody against human and bovine GBM, but not to rat GBM. Acidic residues and the full length 36-mer were important in production of GBM reactive antibodies. Positive controls developed antibody to GBM without reactivity against 36-mer, had IgG and fibrin on the basement membrane, GN and proteinuria. Kidney eluted antibody was reactive with rat, bovine, and human GBM but not 36-mer. GN rat lymphocytes underwent blast transformation to GBM but not peptide, and peptide immunized animals responded only to the respective peptides. None of the animals immunized with GP peptide epitope, despite the development of anti-peptide antibodies or anti-GBM antibodies, developed any in vivo fixation of antibody to the GBM, abnormal proteinuria, or GN. The present study shows that the GP epitope is sufficient to induce an immune response to the epitope, but it is not sufficient to induce GN. This demonstrates that other factors or epitopes are important in the pathogenicity of GBM induced GN in this model. These remain to be delineated.
The purpose of this study was to identify barriers to the management of pain in long-term care institutions. Formal caregivers practising in four long-term care institutions in Hamilton, Ontario participated in eight focus groups. Participants included 6 physicians, 19 registered nurses, 8 registered practical nurses, 13 health care aides and 8 occupational therapists or physiotherapists. Three types of barriers were found: caregiver-related, patient-related and systems-related. Four themes for facilitating pain management were identified: (a) caregivers knowing the patient, (b) family support, (c) caregivers demonstrating understanding and compassion, and (d) teamwork by caregivers. Formal caregivers practising in long-term care institutions encounter a multitude of barriers that hinder the adequate assessment and treatment of pain, such as caregiver beliefs and knowledge and cognitive impairment in patients. Innovative strategies and strong political will are needed to overcome them.
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