Group A streptococcal (GAS) infection induces the production of Abs that cross-react with host neuronal proteins, and these anti-GAS mimetic Abs are associated with autoimmune diseases of the CNS. However, the mechanisms that allow these Abs to cross the blood-brain barrier (BBB) and induce neuropathology remain unresolved. We have previously shown that GAS infection in mouse models induces a robust Th17 response in nasal-associated lymphoid tissue (NALT). Here, we identified GAS-specific Th17 cells in tonsils of humans naturally exposed to GAS, prompting us to explore whether GAS-specific CD4+ T cells home to mouse brains following i.n. infection. Intranasal challenge of repeatedly GAS-inoculated mice promoted migration of GAS-specific Th17 cells from NALT into the brain, BBB breakdown, serum IgG deposition, microglial activation, and loss of excitatory synaptic proteins under conditions in which no viable bacteria were detected in CNS tissue. CD4+ T cells were predominantly located in the olfactory bulb (OB) and in other brain regions that receive direct input from the OB. Together, these findings provide insight into the immunopathology of neuropsychiatric complications that are associated with GAS infections and suggest that crosstalk between the CNS and cellular immunity may be a general mechanism by which infectious agents exacerbate symptoms associated with other CNS autoimmune disorders.

No abstract

The Patient Care Travelling Record (PCTR) is a passport-like health-care summary that, in previous research by the authors, has been found to be a feasible and acceptable tool to convey important clinical information about the palliative care patient. This randomized controlled trial was conducted to determine the effectiveness and efficiency of this Record in improving patient mood, decreasing uncertainty, improving satisfaction with health care, reducing use of health-care services, and maximizing pain control. Eligible patients were randomized to receive or not receive the PCTR (completed by nurse or physician and reviewed jointly with the patient). As baseline entry into the study and then at 1 and 2 months, patients completed measures on level of certainty, mood states, satisfaction with care, levels of pain, and health-care services utilization. During the 2-year study period, only 20% (N = 61) of the patients enrolled in a palliative care program in Southern Ontario were eligible for the trial. Of these patients, 18 died, 15 declined to participate, and 7 were emotionally unable to complete the questionnaires. Thus 21 patients completed the trial. With the exception of those age 65 years and over, the patients using the Record reported decreased levels of uncertainty on follow-up. There was no additional use of health-care services, no differences in mood states, pain relief, or satisfaction with health care. It is significant that 80% of palliative patients were not eligible because their physical and psychological status rendered them insufficiently stable to participate in a research study. Because of their vulnerable status, these patients may be ideal for the utilization of the Record in clinical care. Although research in this palliative care population is challenging due to difficulties with recruitment and high dropout rates due to death, the PCTR, which was previously shown to be acceptable and feasible, has now been shown to be effective in reducing patient uncertainty, specifically for adults under 65 years. Indications for future research are described.

In caring for dying patients, physicians and health team members face a number of decisions about how best to proceed with treatment. Many of these decisions carry implications for the life of the patient, either directly or indirectly. Recent discussions about the morality and wisdom of euthanasia provide an excellent stimulus to reexamine the ethical nature of these decisions. This paper reviews five ethical principles, and describes a process of decision-making that can result in two broad paths of action in relation to life-prolonging treatment. Case examples are presented for illustration. Appropriate ethical practice can be differentiated from acting with the primary intent to take life (euthanasia).

There is an increasing trend toward providing palliative care services within general hospitals. The history and work of three hospital palliative care teams is reviewed, one in New York, one in London, and one in Ontario, Canada. The evolution, leadership, structure, functioning, and financing of the teams is discussed. Indicators of success and survival, principally financial support, leadership, and acceptability within hospitals, are considered. It is recommended that the service traditionally limited to oncology patients be extended to other patient groups. It is also recommended that, taking into account cultural and institutional differences, standardized mechanisms be adopted so that services can be systematically audited and changes implemented. Research and education will become increasingly important if services within hospitals are to survive.