Clinical practice guidelines are increasingly being developed in medical settings to provide evidence-based recommendations to guide the clinical care of patients. The development of Clinical practice guidelines for the psychosocial care of patients with medical illness is a newer initiative, and more complex as the target audience includes health care professionals from diverse backgrounds. In Australia, the National Breast Cancer Centre and National Cancer Control Initiative have collaborated to develop Clinical practice guidelines for the psychosocial care of adults with cancer, funded by the Australian Government Department of Health and Ageing. This paper outlines the development of these guidelines in the international context, gives an overview of their content, and describes strategies for their implementation and evaluation.

1. Airway inflammation is a signal feature of human asthma, as is bronchial obstruction and the resultant airflow limitation. An obligatory accompaniment to airway inflammation is increased airway microvascular permeability, which in turn is causally related to bronchial oedema. In this review, we have attempted to describe the mechanisms of increased airway microvascular permeability and its relationship to oedema, bronchial obstruction and the hyperreactivity to spasmogenic stimuli which are such common features of asthma. 2. It is now clear that bronchial obstruction in chronic asthma can involve bronchial wall oedema and swelling in addition to reversible, elevated airway smooth muscle tone, mucus hypersecretion and airway plugging and potentially permanent structural changes in airway architecture. Inflammatory mediators released in the airway wall in asthma including histamine, platelet-activating factor, leukotrienes and bradykinin are potent inducers of increased bronchial microvascular permeability and are thus promoters of bronchial oedema, airway wall swelling and reduction in luminal calibre. 3. The primary mechanism believed to underlie acute increases in microvascular permeability is contraction of post-capillary venular endothelial cells, resulting in the formation of gaps between otherwise tightly associated cells. Extravasated plasma distributes to the interstitial spaces in the airway wall, resulting in oedema and swelling, but may also traverse the epithelium and collect in the airway lumen. 4. Luminal plasma may compromise epithelial integrity and cilial function and thus reduce mucus clearance. Plasma proteins may also promote the production of viscous mucus and the formation of luminal mucus plugs. Together, these effects can result in or contribute to airway obstruction and hyper-responsiveness. 5. An understanding of such mechanisms can provide insight concerning novel and effective anti-asthma therapies.

We evaluated the ability of hyperosmolar stimuli to activate afferent nerves in the guinea pig trachea and main bronchi and investigated the neural pathways involved. By using electrophysiological techniques, studies in vitro examined the effect of hyperosmolar solutions of sodium chloride (hypertonic saline) on guinea pig airway afferent nerve endings arising from either vagal nodose or jugular ganglia. The data reveal a differential sensitivity of airway afferent neurons to activation with hypertonic saline. Afferent fibers (both A delta and C fibers) with cell bodies located in jugular ganglia were much more sensitive to stimulation with hypertonic saline, compared with afferent neurons with cell bodies located in nodose ganglia. Additional studies in vivo demonstrated that inhalation of aerosols of hypertonic saline induced plasma extravasation in guinea pig trachea that was mediated via tachykinin NK1 receptors. Identification of a differential sensitivity of guinea pig airway afferent nerves to hypertonic saline leads to the speculation that airway responses to hyperosmolar stimuli may result from activation of afferent neurons originating predominantly from the jugular ganglion.

Objectives-A generalised transient improvement may follow intra-articular administration of glucocorticoids to patients with inflammatory arthropathy. This may represent a systemic anti-inflammatory eVect of glucocorticoid released from the joint, mediated through processes such as altered leucocyte traYcking or suppressed release of pro-inflammatory cytokines. Patients, who had received intraarticular injections of glucocorticoids were therefore studied for evidence of these two systemic eVects. Methods-Patients with rheumatoid arthritis were studied. Peripheral blood leucocyte counts, tumour necrosis factor (TNF ) release by peripheral blood monocytes, blood cortisol concentrations, and blood methylprednisolone concentration were measured for 96 hours after intraarticular injection of methylprednisolone acetate. Results-Measurable concentrations of methylprednisolone were present in blood for up to 96 hours after injection. Significant suppression of the hypothalamic-pituitary-adrenal axis persisted throughout this time. Altered monocyte and lymphocyte traYcking, as evidenced by peripheral blood monocytopenia and lymphopenia, was apparent by four hours after injection and resolved in concordance with the elimination of methylprednisolone. Granulocytosis was observed at 24 and 48 hours. Release of TNF by endotoxin stimulated peripheral blood monocytes was suppressed at four hours and thereafter. Suppression was maximal at eight hours and was largely reversed by the glucocorticoid antagonist, mifepristone. Conclusions-After intra-articular injection of methylprednisolone, blood concentrations of glucocorticoid are suYcient to suppress monocyte TNF release for at least four days and to transiently alter leucocyte traYcking. These eVects help to explain the transient systemic response to intra-articular glucocorticoids. Suppression of TNF is principally a direct glucocorticoid eVect, rather than a consequence of other methylprednisolone induced changes to blood composition.