Beyond the benzodiazepines: The search for new anxiolytics. A summary of pre-clinical approaches

The clinical efficacy of the benzodiazepines in reducing anxiety is widely accepted. However, the search for novel anxiolytics continues, motivated by the hope of finding a non-sedative anxiolytic. This article reviews the pre-clinical evidence for new compounds as it relates both to their anxiolytic actions in animal tests and to their sedative potential. Drugs acting at sites on the GABA-benzodiazepine receptor complex are discussed, as well as the potential importance of aminergic and peptidergic pathways.     

Immune therapy of lupus: what is on the horizon?

Systemic lupus erythematosus (SLE) is a complex disease whichhas posed a continuing challenge to scientists and cliniciansof diverse areas of specialization. It serves as a model forthe study of the mechanisms of autoimmunity—providingan important basis for the development of novel targeted therapiesin lupus and related conditions. The pathophysiology of SLE stems from the abnormal clearanceof apoptotic cells and/or endothelial activation. Material fromdying cells such as apoptotic blebs that are not efficientlyremoved may act as antigenic stimuli and lead to the developmentof autoantibodies with consequent formation of immune complexesand an inflammatory response in a variety of organ systems [1].This     

Albuterol Delivery by Metered-Dose Inhaler With a Pediatric Mechanical Ventilatory Circuit Model

Study Objective . To determine albuterol delivery by metered-dose inhaler (MDI) in an in vitro pediatric mechanical ventilatory circuit model. The influence of a spacing device, endotracheal tube (ETT) diameter and length, and air humidity was also investigated. Design . An albuterol MDI canister was connected to an AeroVent spacer or Airlife MDI adapter and ETT 4.0, 5.0, or 6.0 mm at commercially available and equal lengths. The ETT tip was attached to an in-line filter holder with a 1-μm type A/E glass fiber filter. Ventilator settings were fractional concentration of inspired oxygen 50%, tidal volume 250 ml, inspiratory:expiratory (I:E) ratio 1:3, rate 25 breaths/minute, temperature 35°C, and a decelerating flow pattern. Ten albuterol canisters were activated two times each (total 2000 μg) into dry (4.0-, 5.0-, and 6.0-mm ETT) and humidified air (4.0- and 6.0-mm ETT) and repeated in triplicate. Percentage MDI output was determined by weighing the filter before and after drug administration (balance sensitivity 10 μg). Significant differences (p≤0.05) among the groups with and without a spacer and in dry and humidified air were determined by ANOVA with Scheffe's multiple comparison test. Multiple regression was used to determine significant associations between ETT diameter and length and delivery. Main Results . With the AeroVent spacer in humidified air, delivery with the 4.0- and 6.0-mm ETT was approximately 2.3% and 5%, respectively. The spacer and dry air significantly improved delivery. Conclusions . In humidified air, the dose of albuterol by MDI with an AeroVent spacer should be doubled for children intubated with 6.0-mm ETT, and four puffs administered for every one puff desired for 4.0-mm ETT. The results of this investigation should prove useful in initial clinical trials of albuterol MDI in ventilator-dependent infants and children.     

Raised corticosterone in the rat after exposure to the elevated plus-maze

Rats given one or two 5-min trials in the elevated plus-maze had plasma corticosterone concentrations significantly higher than the home cage control group and there was no sign of habituation in the group given two trials. In rats given two plus-maze trials the corticosterone responses were significantly higher in the group given 10-min rather than 5-min trials. A previous experience of cat odour (1 week earlier) has no effect on the plasma corticosterone response, but did have an anxiogenic effect that could be detected by a decrease in the percentage of time spent on the open arms of the plus-maze. The results are discussed with reference to the nature of anxiety generated by trials 1 and 2 and by the trial duration in the plus-maze, and with respect to dissociation between behavioural and endocrinological measures.     

Measuring clinical outcome

At the present time, there are many fundamental issues coming from the Department of Health or from other national organizations, which will have an effect on the future development of the dietetic profession. The British Diatetic Association (BDA) Professional Development Committee will consider these issues, as and when appropriate, and will publish the information in the form of Briefing Papers.
The first Briefing Paper on 'Quality Assurance' was published by the BDA in November 1989. The second on 'Measuring clinical outcome' is published below. In each case the opinion of BDA members and specialist groups has been sought and the Professional Development Committee wishes to thank individuals and the specialist groups for their comments.
The Briefing Papers are intended to provide information and promote discussion among the membership. I would welcome further comments from readers, which may be directed to the British Dietetic Association Office.     

Practice guidelines: the radiology perspective

Clinical practice guidelines have emerged as a reality for medical practitioners over the past 20 years. Although virtually all groups interested in the development of practice guidelines hope for improvements in patient care, secondary expectations vary widely among those using them. Their use in daily practice by physicians has met with resistance from barriers including concerns of “cookbook” medicine, a loss of autonomy, and increased professional liability. The recent experience of the ACR in addressing these challenges illustrates that physicians are receptive to steps perceived to mitigate the risks accompanying the use of guidelines as well as to efforts to increase their understanding of implementing guidelines in clinical practice. The experiences of other medical societies and an inventory of future trends reveal additional challenges associated with the use of practice guidelines, as third parties look to guidelines as points of reference for gauging the performance of health care providers.     

Challenges in accessing multidisciplinary pain treatment facilities in Canada

PURPOSE: The objective of this survey was to examine the services offered by multidisciplinary pain treatment facilities (MPTFs) across Canada and to compare access to care at these MPTFs. METHODS: A MPTF was defined as a clinic that advertised specialized multidisciplinary services for the diagnosis and management of patients with chronic pain, having a minimum of three different health care disciplines (including at least one medical speciality) available and integrated within the facility. The search method included approaching all hospital and rehabilitation centre administrators in Canada, the Insurance Bureau of Canada, the Workplace Safety and Insurance Board or similar body in each province. Designated investigators were responsible for confirming and supplementing MPTFs from the preliminary list for each province. Administrative leads at each eligible MPTF were asked to complete a detailed questionnaire regarding their MPTF infrastructure, clinical, research, teaching and administrative activities. RESULTS: Completed survey forms were received from 102 MPTFs (response rate 85%) with 80% concentrated in major cities, and none in Prince Edward Island and the Territories. The MPTFs offer a wide variety of treatments including non-pharmacological modalities such as interventional, physical and psychological therapy. The median wait time for a first appointment in public MPTFs is six months, which is approximately 12 times longer than non-public MPTFs. Eighteen pain fellowship programs exist in Canadian MPTFs and 64% engage in some form of research activities CONCLUSION: Canadian MPTFs are unable to meet clinical demands of patients suffering from chronic pain, both in terms of regional accessibility and reasonable wait time for patients' first appointment.