In order to determine whether matrix metalloproteinases (MMPs) contribute to inflammation in asthma, we have examined the release of MMPs in bronchoalveolar lavage (BAL) fluids and their production and regulation by alveolar macrophages (AM), in short-term culture. BAL was collected from 38 asthmatic subjects (24 untreated and 14 treated with inhaled corticosteroids), 26 healthy nonsmokers, and 18 patients with chronic bronchitis used as a control group for another inflammation. The profile of MMPs present in BAL fluid and AM supernatant, determined by zymographic analysis, was found to be similar in all populations. The main enzyme released was identified immunologically as MMP-9, a potent collagenolytic and elastolytic enzyme. Its release, measured using enzyme immunoassay, was significantly enhanced in fluids and in AM supernatants from untreated asthmatics compared with those from the other populations. Enhanced MMP-9 levels, in asthma, could not be explained by a different sensitivity of AM to interleukin-4, interferon-gamma, or dexamethasone, compounds that have been shown to inhibit MMP-9. The phorbol ester phorbol 12-myristate 13-acetate (PMA), a protein kinase C (PKC) activator, significantly increased MMP-9 in AM from healthy control subjects but not in those from untreated asthmatics. Calphostin C and H7, PKC inhibitors, significantly reduced PMA-stimulated MMP-9 release in AM from healthy control subjects and spontaneous MMP-9 release in AM from untreated asthmatics. H8, a PKA inhibitor, was inactive in both populations. These data suggest that the stimulation of MMP-9 release in AM from untreated asthmatic patients occurs, at least partly, via signals activating PKC.

Background: Peripheral muscle weakness can be caused by both peripheral muscle and neural alterations. Although peripheral alterations cannot totally explain peripheral muscle weakness in COPD, the existence of an activation deficit remains controversial. The heterogeneity of muscle weakness (between 32 and 57% of COPD patients) is generally not controlled in studies and could explain this discrepancy. This study aimed to specifically compare voluntary and stimulated activation levels in COPD patients with and without muscle weakness. Methods: Twenty-two patients with quadriceps weakness (COPD MW), 18 patients with preserved quadriceps strength (COPD NoMW) and 20 controls were recruited. Voluntary activation was measured through peripheral nerve (VA peripheral) and transcranial magnetic (VA cortical) stimulation. Corticospinal and spinal excitability (MEP/Mmax and Hmax/Mmax) and corticospinal inhibition (silent period duration) were assessed during maximal voluntary quadriceps contractions. Results: COPD MW exhibited lower VA cortical and lower MEP/Mmax compared with COPD NoMW (p < 0.05). Hmax/Mmax was not significantly different between groups (p = 0.25). Silent period duration was longer in the two groups of COPD patients compared with controls (p < 0.01). Interestingly, there were no significant differences between all COPD patients taken together and controls regarding VA cortical and MEP/Mmax. Conclusions: COPD patients with muscle weakness have reduced voluntary activation without altered spinal excitability. Corticospinal inhibition is higher in COPD regardless of muscle weakness. Therefore, reduced cortical excitability and a voluntary activation deficit from the motor cortex are the most likely cortical mechanisms implicated in COPD muscle weakness. The mechanisms responsible for cortical impairment and possible therapeutic interventions need to be addressed.

A small opportunistic study of Stress and Expressed Emotion was undertaken with community mental health workers, who were all case managers or keyworkers to clients with severe mental illness. It was hypothesised that a range of EE ratings would be found in staff, and that they would have high levels of burnout and stress. Job satisfaction was also measured. Ten staff were interviewed about 28 clients. Thirty nine percent of interviewees were rated as high EE (7/10 staff were high EE about at least one client), with low EE interviews showing significantly more warmth. Emotional exhaustion, depersonalisation and GHQ levels were above norms for the general population, and were similar to those found in other inner city community teams, but were not related to EE levels. Nevertheless personal accomplishment and job satisfaction were high. High EE interviews were related to increased client symptomatology. Implications for long term community care are discussed.

Case management has been an integral part of psychiatric practice in the United States for over a decade and has generated a large body of literature. The application of case management principles to the care of people suffering from psychiatric disorders is becoming increasingly popular in the United Kingdom and Europe and literature is now beginning to be published. However, no definitive statements about the efficacy of case management have been made due to a range of conceptual and methodological problems. The present paper is a critical review of the case management outcome literature. Reported outcomes are reviewed in the context of study design and service characteristics. The authors conclude that case management practice can have at least some impact on patients' use of services (including marked decrease in in-patient bed days); satisfaction with services; engagement with services; and social networks and relationships when it is delivered as a direct, clinical service with high staff: patient ratios. A set of recommendations are suggested for the future practice and presentation of research into case management.