A community of practice to address system-based issues and promote clinical leadership among trainee medical officers in a large public health service: an evaluation of a trainee-led forum.

Clinical leadership is necessary to improve the performance of large public hospitals. Trainee medical officers (TMOs) are important stakeholders in organisation-wide initiatives that affect the medical workforce and support clinician engagement. This case study describes the development of a representative body known as the 'TMO Forum' within the Central Adelaide Local Health Network as a mechanism to promote engagement between medical trainees and the hospital executive to facilitate escalation and discussion of system-based issues.

[Inter- and intraindividual pharmacokinetic variations in the treatment of Parkinson's disease].

In the treatment of Parkinson's disease, levodopa, DCI, MAO-B inhibitor, COMT inhibitors, dopamine receptor agonists, amantadine, anticholinergics have been applied and new drugs are being developed. Levodopa is still the golden standard in the treatment of Parkinson's disease. The study on levodopa bioavailability showed 3-4 times differences in individual patients.

Unity from diversity: the evidential use of anecdotal reports of adverse drug reactions and interactions.

Anecdotal case reports contribute about one-third of the published literature on adverse drug reactions and interactions, but are regarded as providing poor-quality evidence. However, they can occasionally provide proof of cause and effect, and there are many other reasons for publishing them. Because an anecdote is a narrative, narratological paradigms from literature, art, and music can show how we can make evidential use of anecdotes.

Treatment gap in the use of lipid-lowering drug therapy in diabetes: a population-based study.

Background: Lowering cholesterol is highly effective in reducing morbidity and mortality in high-risk people with prevalent cardiovascular disease.

Aims: To investigate lipid-lowering therapy use for secondary prevention of coronary heart disease in all diabetic patients in Tayside, Scotland.

Methods: Among the 385,500 Tayside residents on 31 March 2001, the DARTS database identified all people with Types 1 and 2 diabetes with prevalent macrovascular disease, defined as a history of angina or coronary heart disease.

Joining the DoTS: new approach to classifying adverse drug reactions.

A new classification system for adverse drug reactions based on time course and susceptibility as well as dose responsiveness should improve drug development and management of adverse reactions

Bi-phasic change in BDNF gene expression following antidepressant drug treatment.

The gene for brain derived neurotrophic factor (BDNF) has recently received attention in relation to the therapeutic action of antidepressant treatment. This study aimed to clarify the influence of post drug interval on the effect of acute and repeated treatment with antidepressant drugs on BDNF gene expression in the rat brain. It was found that repeated administration of either the monoamine oxidase inhibitor tranylcypromine (TCP) or 5-hydroxytryptamine (5-HT) re-uptake inhibitors (fluoxetine, paroxetine and sertraline), evoke a bi-phasic and time-dependent effect on BDNF gene expression in the rat hippocampus (especially dentate gyrus).

Increasing plasma potassium with amiloride shortens the QT interval and reduces ventricular extrasystoles but does not change endothelial function or heart rate variability in chronic heart failure.

Objectives: To test whether simply increasing plasma potassium with amiloride would exert any of the same beneficial effects on "surrogate outcome measures" that are seen with spironolactone. The latter has been shown to improve mortality in chronic heart failure, possibly as a result of improvements in endothelial dysfunction, vascular angiotensin converting enzyme (ACE), autonomic function, myocardial fibrosis, ventricular arrhythmias, and QT interval indices.

Design: Randomised, placebo controlled trial.

Aldosterone induces acute endothelial dysfunction in vivo in humans: evidence for an aldosterone-induced vasculopathy.

Experimental studies have suggested a role for aldosterone and glucocorticoids in the pathogenesis of endothelial dysfunction. We therefore set out to characterize the acute effects of these hormones on vascular function in vivo in normal humans. A randomized, placebo-controlled, double-blind crossover study was performed on 16 healthy male volunteers (aged 19-29 years), examining the vascular effects of acute intravenous aldosterone infusion (12 pmol.

5-HT2A receptor activation leads to increased BDNF mRNA expression in C6 glioma cells.

It has recently been suggested that an increase in brain-derived neurotrophic factor (BDNF) expression may mediate some of the therapeutic effect of antidepressant drugs, via their effects on the neurotransmitter 5-hydroxytryptamine (5-HT). However, because it is unclear whether 5-HT manipulations directly affect BDNF expression, we examined BDNF mRNA levels in C6 glioma cells following incubation with 5-HT using reverse transcription polymerase chain reaction (RT-PCR) and Northern blot analysis. Incubation of C6 glioma cells with 5-HT increased the BDNF mRNA expression approx twofold.

Studies on the role of calcium in the 5-HT-stimulated release of glutamate from C6 glioma cells.

We recently reported that 5-hydroxytryptamine(2A) (5-HT(2A)) receptor activation on cultured glial cells induces glutamate release [J. Neurosci. Res.

The effect of fluvoxamine and sertraline on the opioid withdrawal syndrome: a combined in vivo cerebral microdialysis and behavioural study.

A microdialysis study was undertaken to determine the effect of acute and sub-chronic administration of the selective serotonin reuptake inhibitor, fluvoxamine, and the acute effect of the selective serotonin reuptake inhibitor sertraline, on the naloxone precipitated opioid withdrawal induced increase in hippocampal noradrenaline levels. This study also determined the effect of fluvoxamine and sertraline on opioid withdrawal-induced physical behaviours. Naloxone (1 mg kg(-1); i.

Adverse drug reactions: keeping up to date.

The amount of published literature on adverse drug reactions is overwhelming; for example, the serial publication Side Effects of Drugs Annual lists and critically discusses over 3000 references each year. As a group, pharmacotherapeutics journals publish more papers on adverse drug reactions than journals that cover other fields, but even so they publish a minority of the total number of papers, and no single journal or group of journals can be highlighted as being a frequent source of primary information. Non-specialists must therefore rely on secondary literature (reviews) and tertiary literature (critical summaries) for information.

Electrical stimulation of the dorsal and median raphe nuclei increases extracellular noradrenaline in rat hippocampus: Evidence for a 5-HT-independent mechanism.

Recent studies have used raphe stimulation combined with in vivo measurements of extracellular dopamine to investigate interactions between the 5-hydroxytryptamine (5-HT) and dopamine systems. Here we have tested whether the same approach can be used to investigate interactions between the 5-HT and noradrenaline systems. Electrical stimulation of the dorsal raphe nucleus (DRN) or median raphe nucleus (MRN) was performed in anaesthetised rats implanted with microdialysis probes in the hippocampus and locus coeruleus (LC).

Gradual reactivation over time of vascular tissue angiotensin I to angiotensin II conversion during chronic lisinopril therapy in chronic heart failure.

Objectives: This study was designed to fully characterize vascular tissue angiotensin I (AI)/angiotensin II (AII) conversion changes over time in vivo in humans during chronic angiotensin-converting enzyme (ACE) inhibitor therapy.

Background: Plasma AII does not remain fully suppressed during chronic ACE inhibitor therapy. However, the plasma renin angiotensin system (RAS) might be dissociated from the vascular tissue RAS.

In vitro evidence that 5-hydroxytryptamine increases efflux of glial glutamate via 5-HT(2A) receptor activation.

Recent studies have established the presence of 5-hydroxytryptamine (5-HT)(2A) receptors on glial cells in culture and in the brain in situ. Here we used cultured C6 glioma cells to investigate the possibility that 5-HT(2A) receptors on glia regulate glutamate release from the cell. The efflux of endogenous glutamate from cultured C6 glioma cells was increased by addition of 5-HT in a concentration-dependent manner (maximal effect +200%).

Cigarette smoking in men and vascular responsiveness.

Aims: Smoking is a major risk factor for developing atherosclerosis. In order to understand the vascular abnormalities observed in smokers, we investigated vascular responsiveness in cigarette smokers.

Methods: We performed two consecutive matched group comparative studies to investigate vascular responsiveness using venous occlusion plethysmography.

Lisinopril improves endothelial function in chronic cigarette smokers.

Cigarette smoking is a pernicious risk factor for the pathogenesis of coronary artery disease, and endothelial dysfunction is an important antecedent event in this process. This is important, as cigarette smoke is directly toxic to endothelial cells. Inhibitors of angiotensin-converting enzyme (ACE) have been shown to improve endothelial function in diabetes and hypercholesterolaemia, and are a promising option in smokers.

Circadian variation in the effects of aldosterone blockade on heart rate variability and QT dispersion in congestive heart failure.

Objectives: The study was designed to comprehensively evaluate the circadian effects of aldosterone blockade on autonomic tone and QT dispersion in chronic heart failure (CHF).

Background: Spironolactone therapy given in addition to angiotensin-converting enzyme inhibitors improved survival in CHF, but the mechanism of its benefit is uncertain. Experimental evidence suggests that aldosterone may have detrimental effects on the autonomic nervous system, especially during the morning hours.

Different tonic regulation of neuronal activity in the rat dorsal raphe and medial prefrontal cortex via 5-HT(1A) receptors.

It has been established that 5-HT(1A) receptors are expressed both presynaptically as autoreceptors by 5-HT containing neurones, and postsynaptically by a variety of other neurones. Activation of either somatodendritic 5-HT(1A) autoreceptors or postsynaptic 5-HT(1A) receptors induces hyperpolarisation and inhibition of action potential discharge of the neurones, but it is unclear whether 5-HT(1A) receptors are under a general tonic influence by 5-HT. In the present study, using single unit recordings from both anesthetized and non-anesthetized rats, we show that the activity of neurones in the medial prefrontal cortex is not altered by systemic administration of the selective 5-HT(1A) receptor antagonist, WAY 100635.

5-HT1A and 5-HT2 receptors differentially regulate the excitability of 5-HT-containing neurones of the guinea pig dorsal raphe nucleus in vitro.

We have used intracellular recording techniques to examine the effects of 5-hydroxytryptamine (5-HT, serotonin) on 5-HT-containing neurones of the guinea pig dorsal raphe nucleus in vitro. Bath-applied 5-HT (30-300 microM) had two opposing effects on the membrane excitability of these cells, reflecting the activation of distinct 5-HT receptor subtypes. As demonstrated previously in the rat, 5-HT evoked a hyperpolarization and inhibition of 5-HT neurones, which appeared to involve the activation of an inwardly rectifying K(+) conductance.

Forbidden fruit.

Although citrus fruits prevent and cure scurvy, they may not always be as good for you as you thought.