Reversible synaptic depression in developing rat CA3 CA1 synapses explained by a novel cycle of AMPA silencing-unsilencing

In the developing hippocampus, experiments using whole cell recordings have shown that a small number of synaptic activations can convert many glutamate synapses to AMPA silent synapses. This depression of AMPA signaling is induced by low-frequency (0.05-0.2 Hz) activation, does not require N-methyl-D-aspartate or metabotropic glutamate receptor activation for its induction, and does not readily reverse after stimulus interruption. Here we show, using field recordings and perforated patch-clamp recordings of transmission in developing CA3-CA1 synapses, that this synaptic depression also can be observed under more noninvasive recording conditions. Moreover, under these conditions, the synaptic depression spontaneously recovers within 20 min by the absence of synaptic activation alone, with a time constant of approximately 7 min as determined by field excitatory postsynaptic potential recordings. Thus as for the expression of long-term potentiation (LTP), recovery from this depression is susceptible to whole cell dialysis ("wash-out"). In contrast to LTP-induced unsilencing, the AMPA signaling after stimulus interruption was again labile, resumed stimulation resulted in renewed depression. The present study has thus identified a novel cycle for AMPA signaling in which the nascent glutamate synapse cycles between an AMPA silent state, induced by a small number of synaptic activations, and a labile AMPA signaling, induced by prolonged inactivity.     

Identification of HLA-DR-bound peptides presented by human bronchoalveolar lavage cells in sarcoidosis

Sarcoidosis is an inflammatory disease of unknown etiology, most commonly affecting the lungs. Activated CD4+ T cells accumulate in the lungs of individuals with sarcoidosis and are considered to be of central importance for inflammation. We have previously shown that Scandinavian sarcoidosis patients expressing the HLA-DR allele DRB1*0301 are characterized by large accumulations in the lungs of CD4+ T cells expressing the TCR AV2S3 gene segment. This association afforded us a unique opportunity to identify a sarcoidosis-specific antigen recognized by AV2S3+ T cells. To identify candidates for the postulated sarcoidosis-specific antigen, lung cells from 16 HLA-DRB1*0301pos patients were obtained by bronchoalveolar lavage. HLA-DR molecules were affinity purified and bound peptides acid eluted. Subsequently, peptides were separated by reversed-phase HPLC and analyzed by liquid chromatography-mass spectrometry. We identified 78 amino acid sequences from self proteins presented in the lungs of sarcoidosis patients, some of which were well-known autoantigens such as vimentin and ATP synthase. For the first time, to our knowledge, we have identified HLA-bound peptides presented in vivo during an inflammatory condition. This approach can be extended to characterize HLA-bound peptides in various autoimmune settings.     

Validation and improvement of a predictive model for treatment outcome in patients with temporomandibular disorders

OBJECTIVE: To examine whether it was possible to improve individual prediction of treatment outcome in patients with temporomandibular disorders (TMD) through continuous quality improvement registrations and implementation of changes in clinical routines. MATERIAL AND METHODS: All 5777 patients referred to a specialist clinic for stomatognathic physiology; 2187 TMD patients started treatment. The patients were divided into Muscle or Mainly TMJ symptom groups. Actual treatment outcome was predicted as Good or Dubious based on patient history and clinical findings. The degree of improvement of initial symptoms was graded using a numeric rating scale 0-100. Improvement in initial complaints of 50% or more was judged as a clinically important difference (CID); 989 patients (76%) completed treatment 1992-1998 (Sample 1) and 769 (86%) treatment 1999-2004 (Sample 2). RESULTS: For patients with Muscle symptoms in Sample 1, CID was reached by 90% of those predicted Good and by 56% of those predicted Dubious. In Sample 2, the figures were Good 93% and Dubious 57%. In subgroup Mainly TMJ symptoms, CID was reached by 94% of those predicted Good and by 88% if predicted Dubious in Sample 1. In Sample 2, the figures were the same for those predicted Good, i.e. 94%, and Dubious, 73%. CONCLUSION: Continuous quality improvement registrations and implementation of changes in clinical routines improved the ability to predict individually the actual treatment outcome between patients predicted Good or Dubious, respectively. Rheumatic disease turned out not to be a negative predictor for treatment outcome.     

Development and evaluation of a questionnaire for measuring patient views of involvement in myocardial infarction care.

BACKGROUND: Patients' involvement in their healthcare has been associated with improved treatment outcomes in chronic illness. Less is known about the affects of patient involvement on the outcomes of acute illness, such as myocardial infarction. A better understanding of patients' views and behaviour during hospitalization might improve clinical practice and enhance patient involvement. AIM: The aim of this study was to develop and evaluate a questionnaire for measuring patients' perceptions of their involvement during hospitalization for myocardial infarction care. METHODS: Focus groups with myocardial infarction patients provided the basis for the construction of the questionnaire. Questionnaire validity and reliability were evaluated in a small pilot study and a larger cross-sectional study among myocardial infarction patients at eleven Swedish hospitals. RESULTS: The questionnaire demonstrated good validity and reliability, with six factors measuring patient views and behaviour regarding involvement. CONCLUSION: The questionnaire appears to be a useful tool for evaluating the perceptions and behaviour of patients regarding patient involvement in myocardial infarction care. Use of this questionnaire may provide insight regarding areas of patient-staff interaction that need improvement. Pinpointing such areas may lead to improved patient involvement, satisfaction with care, and treatment outcomes.     

Intensive care sedation of mechanically ventilated patients: a national Swedish survey.

Sedation in critically ill patients is a complex issue and at the same time an important concept for ensuring patient comfort. The aim of this study was to review the current practice of sedation for patients on mechanical ventilation in Swedish intensive care units (ICUs). Questionnaires were sent by post to head nurses in 89 ICUs with mechanically ventilated patients. By August 2000, 87 (98%) questionnaires had been returned. The results show that mechanically ventilated patients were routinely sedated in 91% of ICUs. Midazolam or propofol in combination with an opioid were the drugs preferred by 76%. Heavy sedation was most usual in 63% of ICUs but, when asked about the sedation level preferred by nurses, 78% chose light sedation (P=0.001). Only 16% used sedation scales. This study indicates that local habits and personal attitudes seem to have a great impact on sedation routines. It therefore appears worthwhile for ICUs to review their practice and, if necessary, to consider implementing sedation scales and sedation guidelines. Research pertaining to potential complications and patient comfort in relation to different sedation levels as well as further validation of the efficacy of sedation scales is needed.