Regional anaesthesia and pain management.

Despite recent advances in analgesia delivery techniques and the availability of new analgesic agents with favourable pharmacokinetic profiles, current evidence suggests that postoperative pain continues to be inadequately managed, with the proportion of patients reporting severe or extreme postoperative pain having changed little over the past decade. Regional techniques are superior to systemic opioid agents with regards to analgesia profile and adverse effects in the context of general, thoracic, gynaecological, orthopaedic and laparoscopic surgery. Outcome studies demonstrate that regional analgesic techniques also reduce multisystem co-morbidity and mortality following major surgery in high risk patients.

5-HT(1A) activation counteracts cardiovascular but not hypophagic effects of sibutramine in rats.

The noradrenaline (NA) and serotonin reuptake inhibitor, sibutramine, gives effective weight loss, but full efficacy cannot be attained at approved doses due to cardiovascular side effects. We assessed in rats the contributions of NA and serotonin transporters to sibutramine's hypophagic and cardiovascular effects, and whether selective 5-hydroxytryptamine (5-HT(1A)) receptor activation could counteract the latter without affecting the former. Food intake was assessed in freely feeding rats and cardiovascular parameters in conscious telemetered rats.

The effects of different analgesic regimens on transcutaneous CO2 after major surgery.

Ventilatory impairment may be detected by a rise in transcutaneous carbon dioxide levels (PtcCO(2)). This observational study assessed the clinical utility of PtcCO(2) monitoring in the postoperative period, and quantified the effect of different peri-operative analgesic regimens on postoperative respiratory function. Following pre-operative baseline PtcCO(2) recording, continuous PtcCO(2) monitoring was performed in 30 patients after major colorectal surgery for up to 24 h.

GPR119 agonists as potential new oral agents for the treatment of type 2 diabetes and obesity.

Background: GPR119 is a Gαs-protein-coupled receptor expressed predominantly in pancreatic islets and gastrointestinal tract in humans.

Objective/methods: To review the available literature on GPR119 agonists.

Results: GPR119 de-orphanisation indicates two classes of possible endogenous agonists, phospholipids and fatty acid amides, with oleoylethanolamide and N-oleoyldopamine being the most potent.

Advances in patient-controlled analgesia: the role of fentanyl ITS.

Effective pain relief is an essential component of a patient's peri-operative care package. Good analgesia has been shown to reduce the incidence of cardiovascular, respiratory and thrombo-embolic complications following surgery. Satisfactory analgesia facilitates early patient ambulation following surgery, which may reduce in-patient stay.

Glucokinase activator PSN-GK1 displays enhanced antihyperglycaemic and insulinotropic actions.

Aims/hypothesis: We evaluated the insulinotropic and antihyperglycaemic actions of glucokinase activators (GKAs), especially through acute and subchronic studies in rodent diabetes models with (2R)-2-(4-cyclopropanesulphonylphenyl)-N-(5-fluorothiazol-2-yl)-3-(tetrahydropyran-4-yl)propionamide (PSN-GK1), a novel and potent GKA.

Materials And Methods: The action of PSN-GK1 on or in the following were investigated: (1) on human liver glucokinase, insulin secretion from MIN6 cells and 2-deoxy-D: -[(3)H]glucose (2-DG) uptake into rat hepatocytes; and (2) in Zucker diabetic fatty rats and in non-diabetic C57Bl/6, diabetic db/db and ob/ob mice.

Results: At 5 mmol/l glucose, PSN-GK1 activated glucokinase (4.

Incidence, etiology, and symptomatology of upper respiratory illness in elite athletes.

Purpose: Upper respiratory illness (URI) is the most common medical condition affecting elite athletes. The aims of this study were to identify and evaluate the incidence, pathogenic etiology, and symptomatology of acute URI during a 5-month training and competition period.

Methods: Thirty-two elite and 31 recreationally competitive triathletes and cyclists, and 20 sedentary controls (age range 18.

Nocardia paucivorans--a cause of disseminated nocardiosis.

We describe a 53-year-old man without discernable immunocompromise who presented with cerebral and cutaneous dissemination of primary pulmonary Nocardia paucivorans infection. This report also identifies 32 other patients in our health area with clinical isolates of N. paucivorans over the last 20 years, extending the reported spectrum of disease caused by this organism.

Applying science to drug discovery.

Scientists and science in the pharmaceutical industry rely heavily on the more academically orientated basic research carried out at Universities, for first of all training, but also as a source of new ideas and approaches to drug discovery. Progress in the discovery and development of novel therapeutics benefits from a healthy alliance with, and the output from, more basic research institutions, and the reverse is also true, with many advances in understanding of physiological and pathological processes being as the result of the application of novel targeted molecules. To illustrate this, some examples related to the themes of this meeting from my experiences in three different companies will be described.

Macrolides in cystic fibrosis.

Macrolide antibiotics have been licensed since the 1950s and have an important role in the treatment of a diverse range of infectious diseases. Macrolide antibiotics have antibacterial activity against gram-positive bacteria, some gram-negative bacteria and intracellular pathogens. The spectrum of antibacterial activity combined with excellent intracellular and tissue penetration has led to the extensive use of this class of drugs in respiratory disease.

Diverging regulation of pyruvate dehydrogenase kinase isoform gene expression in cultured human muscle cells.

The pyruvate dehydrogenase complex occupies a central and strategic position in muscle intermediary metabolism and is primarily regulated by phosphorylation/dephosphorylation. The identification of multiple isoforms of pyruvate dehydrogenase kinase (PDK1-4) and pyruvate dehydrogenase phosphatase (PDP1-2) has raised intriguing new possibilities for chronic pyruvate dehydrogenase complex control. Experiments to date suggest that PDK4 is the major isoenzyme responsible for changes in pyruvate dehydrogenase complex activity in response to various different metabolic conditions.

Hendra and Nipah viruses: new zoonotically-acquired human pathogens.

Some of the key features of Hendra and Nipah viruses are summarized in Table 1. The appearance of these new viruses over the last 10 years emphasizes a number of issues. (1) Epidemics of human infectious diseases can occur unexpectedly and with high impact in terms of morbidity and mortality.

Antibiotic therapy for Klebsiella pneumoniae bacteremia: implications of production of extended-spectrum beta-lactamases.

The prevalence of extended-spectrum beta -lactamase (ESBL) production by Klebsiella pneumonia approaches 50% in some countries, with particularly high rates in eastern Europe and Latin America. No randomized trials have ever been performed on treatment of bacteremia due to ESBL-producing organisms; existing data comes only from retrospective, single-institution studies. In a prospective study of 455 consecutive episodes of Klebsiella pneumoniae bacteremia in 12 hospitals in 7 countries, 85 episodes were due to an ESBL-producing organism.

A randomized trial of home vs hospital intravenous antibiotic therapy in adults with infectious diseases.

Objective: Despite widespread adoption of home care services, few randomised trials have compared health outcomes in the hospital and at home. We report a prospective, randomised trial of home versus hospital therapy in adults receiving intravenous (IV) antibiotics. Our objective was to show that home care is a feasible alternative to hospitalisation over a broad range of infections, without compromise to quality of life (QOL) or clinical outcomes.

Macrolides in cystic fibrosis: is there a role?

A spectrum of anti-inflammatory properties, evidence of anti-infective action against Pseudomonas aeruginosa at sub-inhibitory concentrations and positive clinical experience in patients with diffuse panbronchiolitis, a disease with features in common with cystic fibrosis (CF), has prompted research to evaluate the role of macrolide therapy in patients with CF. Newer macrolides such as azithromycin have the advantage of improved tolerability and a prolonged intracellular half-life requiring an infrequent dosing regimen. Results from initial studies suggest a benefit from several months of macrolide therapy in patients with CF.

International prospective study of Klebsiella pneumoniae bacteremia: implications of extended-spectrum beta-lactamase production in nosocomial Infections.

Background: Commonly encountered nosocomially acquired gram-negative bacteria, especially Klebsiella pneumoniae, produce extended-spectrum beta-lactamases (ESBLs) as an antibiotic resistance mechanism.

Objective: To determine whether microbiology laboratories should report the presence of ESBLs and to establish the infection-control implications of ESBL-producing organisms.

Design: Prospective observational study.

Pharmacokinetics and anti-hyperglycaemic efficacy of a novel inhibitor of glycogen phosphorylase, 1,4-dideoxy-1,4-imino-d- arabinitol, in glucagon-challenged rats and dogs and in diabetic ob/ob mice.

Aim: To further characterize the properties of 1,4-dideoxy-1,4-imino-d-arabinitol (DAB), a recently described novel and potent inhibitor of glycogen phosphorylase and potential anti-diabetic agent, we have determined its pharmacokinetic properties in rats, dogs and mice and compared these to its pharmacodynamic anti-hyperglycaemic efficacy.

Methods: Male Sprague Dawley rats, beagle dogs and diabetic Umeå ob/ob mice were administered DAB or 14C-DAB at various doses and by different routes and in either the conscious or the unconscious state and with or without glucagon, as appropriate. At different time points thereafter, blood, tissue and urine samples were withdrawn for analyses of DAB or 14C-DAB, and blood samples were taken for glucose concentration.