Present and future pharacotherapy for heart failure

The pharmacotherapy currently recommended by the American College of Cardiology and the American Heart Association for heart failure (HF) is a diuretic, an angiotensin-converting enzyme inhibitor (ACEI), a β-adrenoceptor antagonist and (usually) digitalis. This current treatment of HF may be improved by optimising the dose of ACEI used, as increasing the dose of lisinopril increases its benefits in HF. Selective angiotensin receptor-1 (AT1) antagonists are effective alternatives for those who cannot tolerate ACEIs. AT1 antagonists may also be used in combination with ACEIs, as some studies have shown cumulative benefits for the combination. In addition to being used in Stage IV HF patients, in whom it has a marked benefit, spironolactone should be studied in less severe HF and in the presence of β-blockers. The use of carvedilol, extended-release metoprolol and bisoprolol should be extended to severe HF patients as these agents have been shown to decrease mortality in this group. The ancillary properties of carvedilol, particularly antagonism at prejunctional β-adrenoceptors, may give it additional benefits to selective β1-adrenoceptor antagonists. Celiprolol and bucindolol are not the β-blockers of choice in HF, as they do not decrease mortality. Although digitalis does not reduce mortality, it remains the only option for a long-term positive inotropic effect, as the long-term use of the phosphodiesterase inhibitors is associated with increased mortality. The calcium sensitising drug levosimendan may be useful in the hospital treatment of decompensated HF to increase cardiac output and improve dyspnoea and fatigue. The antiarrhythmic drug amiodarone should probably be used in patients at high risk of arrhythmic or sudden death, although this treatment may soon be superseded by the more expensive implanted cardioverter defibrillators, which are probably more effective and have fewer side effects. The natriuretic peptide nesiritide has recently been introduced for the hospital treatment of decompensated HF. Novel drugs that may be beneficial in the treatment of HF include the vasopeptidase inhibitors and the selective endothelin-A receptor antagonists but these require much more investigation. However, disappointing results have been obtained in a large clinical trial of the tumour necrosis factor α antagonist etanercept, where no likelihood of a difference between placebo and etanercept was observed. Small clinical trials with recombinant growth hormone to thicken ventricles in dilated cardiomyopathy have given variable results.

Therapeutic potential of selective superoxide dismutase mimetics

Selective superoxide dismutase (SOD) mimetics are potentially useful in pathological conditions in which there is an overproduction of the superoxide anion O-2.(-). These pathological conditions include inflammation, ischemia/reperfusion, shock, various cardiovascular disorders, amyotrophic lateral sclerosis (ALS) and other neurodegenerative disorders. A major step forward in this field was the development of small-molecule selective SOD mimetics that penetrate cell membranes, These selective SOD mimetics catalytically remove O-2.(-) without interfering with nitric oxide (NO), peroxynitrite (ONOO-) or other radicals such as hydroxyl radical or hydrogen peroxide (H2O2). These selective SOD mimetics (SC-52608, SC-55858, M-40403 and M-40401) have been shown to have benefits in animal models of inflammation, ischemia/reperfusion, shock, thrombosis and diabetes. The next challenge with selective SOD mimetics is to develop therapeutic potential into therapeutic agents.

Roles of fibroblast growth factors in the inner ear

The basic biology of the fibroblast growth factor (FGF) receptors and their splice variants is first reviewed, followed by a review of the known roles of FGFs in the inner ear. They include induction of the otocyst by FGF19, followed by FGF3 in further development of the otocyst. In later development, FGF3 or FGF10 acting on FGF receptor 2b is likely to be involved in development of the walls of the cochlear spaces, while FGF receptor 3 is involved in differentiation of the pillar cells of the organ of Corti. FGF1 and FGF2 act as trophic factors for the developing cochlear nerve fibres. Copyright (C) 2002 S. Karger AG, Basel.

Rapid genotyping of loci involved in antifolate drug resistance in Plasmodium falciparum by primer extension

Current methods used to genotype point mutations in Plasmodium falciparum genes involved in resistance to antifolate drugs include restriction digestion of PCR products, allele-specific amplification or sequencing. Here we demonstrate that known point mutations in dihydrofolate reductase and dihydropteroate synthase can be scored quickly and accurately by single-nucleotide primer extension and detection of florescent products on a capillary sequencer. We use this method to genotype parasites in natural infections from the Thai-Myanmar border. This approach could greatly simplify large-scale screening of resistance mutations of the type required for evaluating and updating antimalarial drug treatment policies. The method can be easily adapted to other P. falciparum genes and will greatly simplify scoring of point mutations in this and other parasitic organisms. © 2002 Australian Society for Parasitology Inc. Published by Elsevier Science Ltd. All rights reserved.

Diabetes detection in Australian general practice: a comparison of diagnostic criteria

Objectives: To study the influence of different diagnostic criteria on the prevalence of diabetes mellitus and characteristics of those diagnosed. Design and setting: Retrospective analysis of data from the general-practice-based Australian Diabetes Screening Study (January 1994 to June 1995). Participants: 5911 people with no previous diagnosis of diabetes, two or more symptoms or risk factors for diabetes, a random venous plasma glucose (PG) level > 5.5 mmol/L and a subsequent oral glucose tolerance test (OGTT) result. Main outcome measure: Prevalence of undiagnosed diabetes based on each of three sets of criteria: 1997 criteria of the American Diabetes Association (ADA), 1996 two-step screening strategy of the Australian Diabetes Society (ADS) (modified according to ADA recommendations about lowered diagnostic fasting PG level), and 1999 definition of the World Health Organization (WHO). Results: Prevalence estimates for undiagnosed diabetes using the American (ADA), Australian (ADS) and WHO criteria (95% CI) were 9.4% (8.7%-10.1%), 16.0% (15.3%-16.7%) and 18.1% (17.1%-19.1%), respectively. People diagnosed with diabetes by fasting PG level (common to all sets of criteria) were more likely to be male and younger than those diagnosed only by 2 h glucose challenge PG level (Australian and WHO criteria only). The Australian (ADS) stepwise screening strategy detected 88% of those who met the WHO criteria for diabetes, including about three-quarters of those with isolated post-challenge hyperglycaemia. Conclusion: The WHO criteria (which include an OGTT result) are preferable to the American (ADA) criteria (which rely totally on fasting PG level), as the latter underestimated the prevalence of undiagnosed diabetes by almost a half. The Australian (ADS) strategy identified most of those diagnosed with diabetes by WHO criteria.

An overview of APSIM, a model designed for farming systems simulation

The Agricultural Production Systems Simulator (APSIM) is a modular modelling framework that has been developed by the Agricultural Production Systems Research Unit in Australia. APSIM was developed to simulate biophysical process in farming systems, in particular where there is interest in the economic and ecological outcomes of management practice in the face of climatic risk. The paper outlines APSIM's structure and provides details of the concepts behind the different plant, soil and management modules. These modules include a diverse range of crops, pastures and trees, soil processes including water balance, N and P transformations, soil pH, erosion and a full range of management controls. Reports of APSIM testing in a diverse range of systems and environments are summarised. An example of model performance in a long-term cropping systems trial is provided. APSIM has been used in a broad range of applications, including support for on-farm decision making, farming systems design for production or resource management objectives, assessment of the value of seasonal climate forecasting, analysis of supply chain issues in agribusiness activities, development of waste management guidelines, risk assessment for government policy making and as a guide to research and education activity. An extensive citation list for these model testing and application studies is provided. Crown Copyright (C) 2002 Published by Elsevier Science B.V. All rights reserved.

Cleaner fish drives local fish diversity on coral reefs

Coral reefs are one of the most diverse habitats in the world [1], yet our understanding of the processes affecting their biodiversity is limited [1-3]. At the local scale, cleaner fish are thought to have a disproportionate effect, in relation to their abundance and size, on the activity of many other fish species, but confirmation of this species' effect on local fish diversity has proved elusive. The cleaner fish Labroides dimidiatus has major effects on fish activity patterns [4] and may indirectly affect fish demography through the removal of large numbers of parasites [5, 6]. Here we show that small reefs where L. dimidiatus had been experimentally excluded for 18 months had half the species diversity of fish and one-fourth the abundance of individuals. Only fish that move among reefs, however, were affected. These fish include large species that themselves can affect other reef organisms [2, 7]. In contrast, the distribution of resident fish was not affected by cleaner fish. Thus, many fish appear to choose reefs based on the presence of cleaner fish. Our findings indicate that a single small [8] and not very abundant [9] fish has a strong influence on the movement patterns, habitat choice, activity, and local diversity and abundance of a wide variety of reef fish species.

Anomalies in the developing neural and visceral head skeleton of the Australian lungfish, Neoceratodus forsteri

Several anomalies occur in the developing neural and visceral head skeleton of young specimens of Neoceratodus forsteri that have been reared under laboratory conditions. These include anomalies of the basicranium and its derivatives, aberrations of the anterior mandible and hyoid apparatus, and abnormalities in the articulation of the jaws and the elements that produce them. Apart from the occasional absence of the basihyal, and failure of the quadrate processes to form, the anomalies are not deficiencies. Most involve malformations of parts of the neurocranium and visceral skeleton, inappropriate articulations or fusions between elements, disunity in structures that are normally fused and the appearance of supernumerary elements. The incidence of chondral anomalies, generally higher than aberrations that occur in the dermal skeleton in juvenile lungfish, ranges from 1-10% in laboratory reared individuals that have not been subjected to experimental interference. The anomalies differ from those found in many amphibian populations, in the field and in the laboratory, because they involve the cranium, and not the limbs, and the lungfish have not been exposed to the factors that cause anomalies in the amphibians. It is unlikely that the existence of those anomalies, if it is reflected in the wild population, places a selective pressure on the lungfish, because, in a normal season, less than 1% of the total number of eggs produced survive to be recruited into the adult population.

An overview of drugs and ancillary equipment for the dentist's emergency kit

The concept of a basic (i.e., essential) medical emergency kit suitable for a general dental practitioner varies somewhat between different authorities. A practitioner's choice is also dependant on the proximity of medical aid and the nature of the dental practice. Over recent years the trend has been to restrict the items to a minimum, in the interest of both common sense and safety, for example, just oxygen, adrenaline 1:1000, an oral carbohydrate source, glyceryl trinitrate and aspirin as first options. Ancillary equipment should include an oxygen therapy facemask, a pocket mask and a set of oral (Guedel) airways. Two further medication options for consideration are an aerosol bronchodilator and, in certain circumstances, an injectable antihypoglycaemic agent. This paper provides a selective overview of the subject. An absolute necessity is for dentists to be competent in Basic Life Support skills, and to maintain a complete and current medical history for all patients.

Diagnosis and management of unusual dental abscesses in children

Although the majority of dental abscesses in children originate from dental caries or trauma, a few are associated with unusual conditions which challenge diagnosis and management. Recent research findings have shed light on these unusual entities and greatly improved understanding of their clinical implications. These conditions include developmental abnormalities such as dens invaginatus in which there is an invagination of dental tissues into the pulp chamber and dens evaginatus in which a tubercle containing pulp is found on the external surface of a tooth crown. In addition, inherited conditions which show abnormal dentine such as dentine dysplasia, dentinogenesis imperfecta, and osteogenesis imperfecta predispose the dentition to abscess formation. Furthermore, 'spontaneous' dental abscesses are frequently encountered in familial hypophosphataemia, also known as vitamin D-resistant rickets, in which there is hypomineralization of dentine and enlargement of the pulp. In addition to developmental conditions, there are also acquired conditions which may cause unusual dental abscesses,. These include pre-eruptive intracoronal resorption which was previously known as 'pre-eruptive caries' or the 'fluoride bomb'. In addition, some undiagnosed infections associated with developing teeth are now thought to be the mandibular infected buccal cysts which originate from infection of the developing dental follicles. In the present paper, these relatively unknown entities Which cause unusual abscesses in children are reviewed with the aim of updating the general practitioner in their diagnosis and management.

Residential mobility in the Seoul metropolitan region: Who, where and why?

This article presents data on residential mobility for the Seoul Metropolitan Region. It addresses two questions-why do households move and who moves and finds that like research undertaken in other cities that a wide range of factors impact on the residential mobility process. Key outcomes include the impact of housing dissatisfaction on residential mobility and the impact that life cycle, period of residence and housing and dwelling characteristics have on discerning between movers and non-movers.

Ubiquitous travel service delivery

Free independent travelers require flexible, reactive service delivery due to their regularly changing location and activities and the lack of a wired Internet connection. A ubiquitous travel service delivery system that is able to dynamically deliver services in response to relevant events, such as changing location, availability of new last-minute specials, work opportunities, and safety issues can provide added value while retaining the flexibility that is so important to independent travelers. This article describes such a system. An engineering design research approach has been adopted to design the system. Issues addressed include traveler and service states and events, contexts, situations, and situation-action rules. An architecture is proposed that is based on distributed, cooperating software agents and mobile data technologies. The role of these agents is to continuously monitor situations that are occurring in the physical and virtual service spaces and to take the required action for any situations that are relevant to the traveler.

Ecological criteria for evaluating candidate sites for marine reserves

Several schemes have been developed to help select the locations of marine reserves. All of them combine social, economic, and biological criteria, and few offer any guidance as to how to prioritize among the criteria identified. This can imply that the relative weights given to different criteria are unimportant. Where two sites are of equal value ecologically; then socioeconomic criteria should dominate the choice of which should be protected. However, in many cases, socioeconomic criteria are given equal or greater weight than ecological considerations in the choice of sites. This can lead to selection of reserves with little biological value that fail to meet many of the desired objectives. To avoid such a possibility, we develop a series of criteria that allow preliminary evaluation of candidate sites according to their relative biological values in advance of the application of socioeconomic criteria. We include criteria that,. while not strictly biological, have a strong influence on the species present or ecological processes. Out scheme enables sites to be assessed according to their biodiversity, the processes which underpin that diversity, and the processes that support fisheries and provide a spectrum of other services important to people. Criteria that capture biodiversity values include biogeographic representation, habitat representation and heterogeneity, and presence of species or populations of special interest (e.g., threatened species). Criteria that capture sustainability of biodiversity and fishery values include the size of reserves necessary to protect viable habitats, presence of exploitable species, vulnerable life stages, connectivity among reserves, links among ecosystems, and provision of ecosystem services to people. Criteria measuring human and natural threats enable candidate sites to be eliminated from consideration if risks are too great, but also help prioritize among sites where threats can be mitigated by protection. While our criteria can be applied to the design of reserve networks, they also enable choice of single reserves to be made in the context of the attributes of existing protected areas. The overall goal of our scheme is to promote the development of reserve networks that will maintain biodiversity and ecosystem functioning at large scales. The values of eco-system goods and services for people ultimately depend on meeting this objective.

New Zealand climate in the Neogene and implications for global atmospheric circulation

New Zealand has a good Neogene plant fossil record. During the Miocene it was without high topography and it was highly maritime, meaning that its climate, and the resulting vegetation, would be controlled dominantly by zonal climate conditions. Its vegetation record during this time suggests the climate passed from an ever-wet and cool but frostless phase in the Early Miocene in which Nothofagus subgenus Brassospora was prominent. Then it became seasonally dry, with vegetation in which palms and Eucalyptus were prominent and fires were frequent, and in the mid-Miocene, it developed a dry-climate vegetation dominated by Casuarinaceae. These changes are reflected in a sedimentological change from acidic to alkaline chemistry and the appearance of regular charcoal in the record. The vegetation then changed again to include a prominent herb component including Chenopodiaceae and Asteraceae. Sphagnum became prominent, and Nothofagus returned, but mainly as the subgenus Fuscospora (presently restricted to temperate climates). This is interpreted as a return to a generally wet, but now cold climate, in which outbreaks of cold polar air and frost were frequent. The transient drying out of a small maritime island and the accompanying vegetation/climate sequence could be explained by a higher frequency of the Sub-Tropical High Pressure (STHP) cells (the descending limbs of the Hadley cells) over New Zealand during the Miocene. This may have resulted from an increased frequency of 'blocking', a synoptic situation which occurs in the region today. An alternative hypothesis, that the global STHP belt lay at a significantly higher latitude in the early Neogene (perhaps 55degreesS) than today (about 30degreesS), is considered less likely because of physical constraints on STHP belt latitude. In either case, the difference between the early Neogene and present situation may have been a response to an increased polar-equatorial temperature gradient. This contrasts with current climate models for the geological past in which the latitude of the High Pressure belt impact is held invariant though geological time. (C) 2003 Elsevier Science B.V. All rights reserved.

NEW Solutions: An Australian health promotion programme for people with mental illness

The prevalence of people who are overweight or obese is continuing to rise. This is a key risk indicator of preventable morbidity and mortality resulting from many diseases. The increase in the number of obese people is associated with dietary practices and a reduction in physical activity. There is a need to implement strategies for the reduction of obesity in at-risk groups. People with a mental illness are at high risk of many physical illnesses related to behavioural factors, which include poor diet and lack of exercise. Health promotion programmes need to be incorporated into mental-health services to improve the general health and wellbeing of people with a mental illness. An Australian psychiatric rehabilitation service developed and implemented a health promotion programme, NEW Solutions, which aimed to address issues related to weight gain, dietary practice and physical inactivity.