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A comparative analysis of the effect of two compounds, dibutyryl–cyclic-AMP (dbcAMP) and latrunculin B, on the morphology and ultrastructure of the dimorphic fungus Mucor rouxiiunder aerobic growth conditions is presented. dbcAMP acts through the sustained activation of protein kinase A, and latrunculin B through the disruption of the actin cytoskeleton. Upon addition of these compounds to the growth medium at any stage of the germination process, cells lost polarised growth and switched to isodiametric growth. The effect was reversible. The morphologies, visualised by light microscopy or scanning electron microscopy (SEM), were alike. A switch from a rough to a smooth surface was observed by SEM when cells were repolarised by removal of the added compound. Ultrastructural changes under both conditions, as observed by transmission electron microscopy, were similar, the main feature being the enlargement of the cell wall, with irregular depositions, and detachment from the cell membrane. dbcAMP-treated cells showed a decrease in the number of glycogen granules compared with control and latrunculin B-treated cells. F-actin staining with fluorescein isothiocyanate–phalloidin showed that both dbcAMP- and latrunculin B-treated cells displayed a much lower fluorescence than control cells, with only a few pale plaques. The results suggest that the sustained activation of protein kinase A, which impairs polarised growth, might exert its effect through a modification of actin cytoskeleton organisation, very probably also involving an integrinlike pathway, as judged by the cell wall detachment and loss of cell adhesiveness of the dbcAMP-treated isodiametric cells.A comparative analysis of the effect of two compounds, dibutyryl–cyclic-AMP (dbcAMP) and latrunculin B, on the morphology and ultrastructure of the dimorphic fungus Mucor rouxiiunder aerobic growth conditions is presented. dbcAMP acts through the sustained activation of protein kinase A, and latrunculin B through the disruption of the actin cytoskeleton. Upon addition of these compounds to the growth medium at any stage of the germination process, cells lost polarised growth and switched to isodiametric growth. The effect was reversible. The morphologies, visualised by light microscopy or scanning electron microscopy (SEM), were alike. A switch from a rough to a smooth surface was observed by SEM when cells were repolarised by removal of the added compound. Ultrastructural changes under both conditions, as observed by transmission electron microscopy, were similar, the main feature being the enlargement of the cell wall, with irregular depositions, and detachment from the cell membrane. dbcAMP-treated cells showed a decrease in the number of glycogen granules compared with control and latrunculin B-treated cells. F-actin staining with fluorescein isothiocyanate–phalloidin showed that both dbcAMP- and latrunculin B-treated cells displayed a much lower fluorescence than control cells, with only a few pale plaques. The results suggest that the sustained activation of protein kinase A, which impairs polarised growth, might exert its effect through a modification of actin cytoskeleton organisation, very probably also involving an integrinlike pathway, as judged by the cell wall detachment and loss of cell adhesiveness of the dbcAMP-treated isodiametric cells.

AbstractAims: To assess the attitudes of Australian doctors towards the use of antithrombotic drug therapy for stroke prevention in patients with non-valvular atrial fibrillation (AF), and investigate the barriers to prescribing warfarin. Methods: A postal survey was undertaken among approximately 10% of all registered general practitioners (GPs), cardiologists and physicians in Australia. The anonymous questionnaire used case scenarios to assess doctors’ knowledge of current guidelines for the therapeutic management of AF and sought opinions on potential barriers to the use of anticoagulation. Results: Completed questionnaires were received from 711 doctors (30% response rate). The GPs performed better than the cardiologists and other specialists in estimating the risk of stroke in case scenarios. However, the cardiologists were more likely to select the recommended treatment, with GPs being more hesitant to use anticoagulation and tending to underestimate its reported benefit for stroke prevention in non-valvular AF. The GPs were also more likely to overestimate the reported risk of major bleeds with warfarin. In contrast, over one-third of the cardiologists went as far as to give warfarin to a low-risk patient and they were more likely to overestimate the reported benefit of aspirin and warfarin in AF. Only half the doctors correctly classified a patient without a previous stroke (but with other risk factors) as being at high risk. Increased experience as a registered medical practitioner was generally related to a poorer performance on classifying patients according to the risk of stroke. The principal barriers to the use of anticoagulation were nominated as: (i) active gastrointestinal bleeding, (ii) previous intracranial haemorrhage, (iii) alcoholism, (iv) a history of daily falls, (v) liver disease, (vi) severe anaemia and (vii) concurrent use of non-steroidal anti-inflammatory drugs. Conclusion: There is scope for improvement in doctors’ knowledge about the appropriate use of antithrombotic drug therapy in non-valvular AF and awareness of the results of recent clinical trials. Compilation and dissemination of clear guidelines and focused education on some of the other risk factors (apart from previous stroke or transient ischaemic attacks) in patients with non-valvular AF are important strategies for targeting barriers to the use of anticoagulation for stroke prevention. (Intern Med J 2002; 32: 15–23)

Background: The benefits of antithrombotic therapy in chronic atrial fibrillation (AF) have been established in clinical trials, but there is a paucity of data on outcomes in practice. Aims: The objective was to establish a large ongoing database of patients with non-valvular AF, to enable the accurate determination of clinical outcomes. Methods: A retrospective review of the medical records for consecutive patients who had AF documented on electrocardiogram at the major teaching hospital in Tasmania between 1 January 1997 and 30 June 1999 was performed. An extensive range of demographic and clinical variables was recorded for all patients with chronic or paroxysmal non-valvular AF. Results: The 505 patients (60% males) included in the database had a median age of 76 years. According to risk stratification criteria, 79% of the patients with previously diagnosed chronic or paroxysmal AF had a high risk of developing stroke at the time of admission to hospital care. However, only one-third (34%) of these patients were receiving warfarin (or warfarin plus aspirin), with almost one-quarter (24%) receiving no antithrombotic agent. The annual incidence of ischaemic strokes was 3.4% (1.5–6.4%; 95% CI) when taking warfarin, compared to 7.0% (5.2–9.4%) for patients not taking warfarin and 7.8% (5.4–11.1%) for patients taking aspirin. The annual incidence of bleeding complications in patients taking warfarin was 14.2% (10.0–19.5%) overall and 3.4% (1.5–6.4%) for major bleeds. In patients not taking warfarin, the overall annual incidence of bleeds was 8.4% (6.3–10.9%) and 3.9% (2.5–5.7%) for major bleeds. Conclusions: Warfarin is underused in patients with AF. In clinical practice, warfarin confers a similar stroke risk reduction to that observed in trials, with an increase in incidence of only minor bleeding complications. Aspirin did not appear to reduce the risk of stroke. (Intern Med J 2001; 31: 329–336)

The article focuses on the development of an optimized pulsed-power generator with integrated radiation detection system. Optimization of the bremsstrahlung source will lead to smaller pulsed-power generators, deployable collimators, and more manageable personnel shielding. There is a need for a repetitively operated pulsed-power generator which requires consideration of available generator architectures, thermal management, size, weight, maintainability, and cost.