Population pharmacokinetics and pharmacodynamics: An underutilized resource

A meeting was convened in Canberra, Australia, at the request of the Australian Drug Evaluation Committee (ADEC), on December 3-4, 1997 to discuss the role of population pharmacokinetics and pharmacodynamics in drug evaluation and development. The ADEC was particularly concerned about registration of drugs in the pediatric age group. The population approach could be used more often than is currently the case in pharmacokinetic and pharmacodynamic studies to provide valuable information for the safe and effective use of drugs in neonates, infants, and children. The meeting ultimately broadened to include discussion about other subgroups. The main conclusions of the meeting were: 1. The population approach, pharmacokinetic and pharmacodynamic analysis, is a valuable tool both for drug registration purposes and for optimal dosing of drugs in specific groups of patients, 2. Population pharmacokinetic and pharmacodynamic studies are able to fill in the gaps' in registration of drugs, for example, to provide information on optimal pediatric dosing. Such studies provide a basis for enhancing product information to improve rational prescribing, 3. Expertise is required to perform the population studies and expertise, with a clinical perspective, is also required to evaluate such studies if they are to be submitted as part of a drug registration dossier Such expertise is available in the Australasian region and is increasing. Centers of excellence with the appropriate expertise to advise and assist should be encouraged to develop and grow in the region, 4. The use of the population approach by the pharmaceutical industry needs to be encouraged to provide valuable information not obtainable by other techniques. The acceptance of population pharmacokinetic and pharmacodynamic analyses by regulatory agencies also needs to be encouraged, and 5. Development of the population approach to pharmacokinetics and pharmacodynamics is needed from a public health perspective to ensure that all available information is collected and used to improve the way drugs are used. This important endeavor needs funding and support at the local and international levels.

Reprocessing and reuse of single-use medical devices used during hemodynamic procedures in Brazil: A widespread and largely overlooked problem

Background. Several medical devices used during hemodynamic procedures, particularly angiographic diagnostic and therapeutic cardiac catheters, are manufactured for single use only. However, reprocessing and reuse of these devices has been reported, to determine the frequency of reuse and reprocessing of single-use medical devices used during hemodynamic procedures in Brazil and to evaluate how reprocessing is performed. Design. National survey, conducted from December 1999 to July 2001. Methods. Most of the institutions affiliated with the Brazilian Society of Hemodynamic and Interventional Cardiology were surveyed by use of a questionnaire sent in the mail. Results. The questionnaire response rate was 50% (119 of 240 institutions). Of the 119 institutions that responded, 116 (97%) reported reuse of single-use devices used during hemodynamic procedures, and only 26 (22%) reported use of a standardized reprocessing protocol. Cleaning, flushing, rinsing, drying, sterilizing and packaging methods varied greatly and were mostly inadequate. Criteria for discarding reused devices varied widely. Of the 119 institutions that responded, 80 (67%) reported having a surveillance system for adverse events associated with the reuse of medical devices, although most of these institutions did not routinely review the data, and only 38 (32%) described a training program for the personnel who reprocessed single-use devices. Conclusions. The reuse of single-use devices used during hemodynamic procedures was very frequent in hospitals in Brazil. Basic guidance on how to reuse and reprocess single-use medical devices is urgently needed, because, despite the lack of studies to support reusing and reprocessing single-use medical devices, such devices are necessary in limited-resource areas in which these practices are current.

Hormonal Contraceptives and the Length of Their Use Are Not Independent Risk Factors for High-Risk HPV Infections or High-Grade CIN

Aims: To evaluate the role of hormonal contraceptives as a risk factor of high-risk human papillomavirus (HR-HPV), cervical intraepithelial lesions (CIN) and cervical cancer in our multi-center population-based LAMS (Latin American Screening) study. Methods: A cohort study with >12,000 women from Brazil and Argentina using logistic regression to analyze the covariates of hormonal contraception (HOC - oral, injections, patches, implants, vaginal ring and progesterone intrauterine system) use followed by multivariate modeling for predictors of HR-HPV and CIN2+. Results: HR-HPV infection was a consistent risk factor of high-grade CIN in all three groups of women. The length of HOC use was not significantly related to high-grade squamous intraepithelial lesions (HSIL)+ Pap (p = 0.069), LSIL+ Pap (p = 0.781) or ASCUS+ (p = 0.231). The same was true with the length of HOC use and histology CIN3+ (p = 0.115) and CIN2+ (p = 0.515). Frequently, HOC users have previously shown more HPV-related lesions, as well as lower HPV prevalence if they were current smokers. But HOC use and time of usage were not independent risk factors of either HR-HPV infection or high-grade CIN using multiple logistic regressions. Conclusions: No evidence was found for an association between the use of HOC with an increased risk for HR-HPV infection or high-grade CIN in this cohort. Copyright (C) 2010 S. Karger AG, Basel

Use and non-use values of wild Asian elephants: A total economic valuation approach

The contingent valuation method is often used for valuing environmental goods possessing use as well as non-use values. This paper investigates the relative importance of these values in relation to the existence of the wild Asian elephant. It does so by analysing results from a contingent valuation survey of a sample of urban residents living in three selected housing schemes in Colombo. We find that the major proportion of the respondents’ willingness to pay (WTP) for conservation of wild elephants is attributable to the non-use values of the elephant. However, differences in the relative importance of these values exist between those who visit national parks and those who do not. Differences in respondents’ WTP for conservation of elephants are found to be largely influenced by attitudinal and behavioural factors rather than socio-economic ones. We conclude that policymakers must recognise and take account of the importance of non-use values of the Asian elephant, if this endangered species is to survive in the long run. Nevertheless, the non-consumptive use value of elephants in Sri Lanka is also found to be substantial.

Management, conservation and farming of saltwater crocodiles: An Australian case study of sustainable commercial use

Opinions differ about what types of policies are likely to be most effective in conserving wildlife species. For example, the Convention on International Trade in Endangered Species of Wild Flora and Fauna (CITES) is based on the premise that curbing the commercial use of endangered species favours their conservation, whereas the Convention on Biological Diversity envisages the possibility that such use may contribute to the conservation of species. In Australia, as illustrated in the case of the saltwater crocodile (Crocodylus porosus), the governments of the Northern Territory and Western Australia have favoured the latter policy in recent years, whereas Queensland has favoured the former approach. The saltwater crocodile management plan of the Northern Territory provides an instructive case study of the consequences of adopting a commercial use strategy to promote wildlife conservation. The methodology used in this study, which involves a survey of crocodile farm managers and managers of cattle properties in the Northern Territory as well as secondary data, is outlined, after providing background on the conservation status of saltwater crocodiles in Australia and the saltwater crocodile management plan of the Northern Territory. In the results section, after outlining the nature and structure of the Northern Territory crocodile farming industry, evidence is presented on whether or not the crocodile management plan of the Northern Territory encourages pastoralists to conserve crocodiles on their properties. This study concludes with a discussion of the overall conservation effectiveness of the crocodile management scheme of the Northern Territory and considers its possible implications for saltwater crocodile management in areas of Asia where the species occurs.

Public attitudes to the use of wildlife by Aboriginal Australians: Marketing of wildlife and its conservation

Indigenous Australians have socioeconomic attributes similar to those of residents in some developing countries. Their utilisation of wildlife could add to their economic opportunities. Attitudes of a sample of the Australian public towards the subsistence use of wildlife by Indigenous Australians and whether or not they should be allowed to sell wildlife and wildlife products are examined. Allowing such possibilities could provide economic incentives for nature conservation among local people. We explore whether those sampled believe that Indigenous Australians should do more than other groups and institutions to conserve Australia's tropical species, and whether or not they should be allowed to take common as well as endangered wildlife species for food. Attitudes of the sampled public towards Indigenous Australians earning income from trophy hunting and from the harvesting of northern long-necked turtles for the pet trade are canvassed. The possible conservation consequences of sale of wildlife by Indigenous Australians are discussed.

Public valuation of and attitudes towards the conservation and use of the Hawksbill turtle: An Australian case study

Managing hawksbill turtle populations for use and conservation requires (i) adequate scientific understanding of their population status and dynamics and (ii) consideration of the public’s attitudes to this species. This study employs experimental surveys to assess the Australian public’s attitudes towards the hawksbill turtle, their knowledge of it, their views about its sustainable commercial harvesting, and their support and financial contribution for the species’ conservation. Contingent valuation reveals that the Australian public’s willingness to contribute to the conservation of the hawksbill turtle is high even in comparison to threatened Australian bird and mammal fauna. Most of this stated contribution is based on the intrinsic (non-use) value associated with the hawksbill turtle. It seems that the Australian public will only accept its harvesting if the sustainability of this is assured and its population is more secure. The CITES categorisation of the hawksbill as an Appendix I species hampers the development of techniques for its sustainable use.

Environmental regulation of land use and public compensation: principles, and Swiss and Australian examples

The authors discuss the regulation of rural land use and compensation for property-rights restrictions, both of which appear to have become more commonplace in recent years but also more contested. The implications of contemporary theories in relation to this matter are examined, including: the applicability of new welfare economics; the relevance of the neoclassical theory of politics; and the implications of contemporary theories of social conflict resolution and communication. Examination of examples of Swiss and Australian regulation of the use of rural properties, and the ensuing conflicts, reveals that many decisions reflect a mixture of these elements. Rarely, if ever, are social decisions in this area made solely on the basis of welfare economics, for instance social cost-benefit analysis. Only some aspects of such decisions can be explained by the neoclassical theory of politics. Theories of social conflict resolution suggest why, and in what way, approaches of discourse and participation may resolve conflicts regarding regulation and compensation. These theories and their practical application seem to gain in importance as opposition to government decisions increases. The high degree of complexity of most conflicts concerning regulation and compensation cannot be tackled with narrow economic theories. Moreover, the Swiss and Australian examples show that approaches involving conflict resolution may favour environmental standards.

Tree use, diet and home range of the koala (Phascolarctos cinereus) at Blair Athol, central Queensland

Free-ranging koalas (Phascolarctos cinereus) were monitored by means of radio-relocation in the area of Blair Athol Coal Mine and surrounding properties. Daytime tree use, home range and diet of these koalas was determined in spring and autumn, as was the leaf moisture composition of potential fodder species. Koalas used on average 93 (male koalas) and 56 (female koalas) trees during the period of observation, occupying home ranges of 135 and 101 ha respectively. Mean sightings per tree were 1.19 for both males and females and home-range sizes were not significantly different between sexes or seasons. Koalas were observed returning to previously used daytime roosting trees infrequently (

The 2000 Ogura Lecture: Olfactory neural cells: An untapped diagnostic and therapeutic resource

Objective. This is an over-view of the cellular biology of upper nasal mucosal cells that have special characteristics that enable them to be used to diagnose and study congenital neurological diseases and to aid neural repair. Study Design: After mapping the distribution of neural cells in the upper nose, the authors' investigations moved to the use of olfactory neurones to diagnose neurological diseases of development, especially schizophrenia. Olfactory-ensheating glial cells (OEGs) from the cranial cavity promote axonal penetration of the central nervous system and aid spinal cord repair in rodents. The authors sought to isolate these cells from the more accessible upper nasal cavity in rats and in humans and prove they could likewise promote neural regeneration, making these cells suitable for human spinal repair investigations. Methods: The schizophrenia-diagnosis aspect of the study entailed the biopsy of the olfactory areas of 10 schizophrenic patients and 10 control subjects. The tissue samples were sliced and grown in culture medium. The ease of cell attachment to fibronectin (artificial epithelial basement membrane), as well as the mitotic and apoptotic indices, was studied in the presence and absence of dopamine in those cell cultures. The neural repair part of the study entailed a harvesting and insertion of first rat olfactory lamina propria rich in OEGs between cut ends of the spinal cords and then later the microinjection of an OEG-rich suspension into rat spinal cords previously transected by open laminectomy. Further studies were done in which OEG insertion was performed up to 1 month after rat cord transection and also in monkeys. Results: Schizophrenic patients' olfactory tissues do not easily attach to basement membrane compared with control subjects, adding evidence to the theory that cell wall anomalies are part of the schizophrenic lesion of neurones. Schizophrenic patient cell cultures had higher mitotic and apoptotic indices compared with control subjects. The addition of dopamine altered these indices enough to allow accurate differentiation of schizophrenics from control patients, leading to, possibly for the first time, an early objective diagnosis of schizophrenia and possible assessment of preventive strategies. OEGs from the nose were shown to be as effective as those from the olfactory bulb in promoting axonal growth across transected spinal cords even when added I month after injury in the rat. These otherwise paraplegic rats grew motor and proprioceptive and fine touch fibers with corresponding behavioral improvement. Conclusions. The tissues of the olfactory mucosa are readily available to the otolaryngologist. Being surface cells, they must regenerate (called neurogenesis). Biopsy of this area and amplification of cells in culture gives the scientist a window to the developing brain, including early diagnosis of schizophrenia. The Holy Grail of neurological disease is the cure of traumatic paraplegia and OEGs from the nose promote that repair. The otolaryngologist may become the necessary partner of the neurophysiologist and spinal surgeon to take the laboratory potential of paraplegic cure into the day-to-day realm of clinical reality.

Low input tillage/cropping systems for limited resource areas

Agriculture in limited resource areas is characterized by small farms which an generally too small to adequately support the needs of an average farm family. The farming operation can be described as a low input cropping system with the main energy source being manual labor, draught animals and in some areas hand tractors. These farming systems are the most important contributor to the national economy of many developing countries. The role of tillage is similar in dryland agricultural systems in both the high input (HICS) and low input cropping systems (LICS), however, wet cultivation or puddling is unique to lowland rice-based systems in low input cropping systems. Evidence suggest that tillage may result in marginal increases in crop yield in the short term, however, in the longer term it may be neutral or give rise to yield decreases associated with soil structural degradation. On marginal soils, tillage may be required to prepare suitable seedbeds or to release adequate Nitrogen through mineralization, but in the longer term, however, tillage reduces soil organic matter content, increases soil erodibility and the emission of greenhouse gases. Tillage in low input cropping systems involves a very large proportion of the population and any changes: in current practices such as increased mechanization will have a large social impact such as increased unemployment and increasing feminization of poverty, as mechanization may actually reduce jobs for women. Rapid mechanization is likely to result in failures, but slower change, accompanied by measures to provide alternative rural employment, might be beneficial. Agriculture in limited resource areas must produce the food and fiber needs of their community, and its future depends on the development of sustainable tillage/cropping systems that are suitable for the soil and climatic conditions. These should be based on sound biophysical principles and meet the needs of and he acceptable to the farming communities. Some of the principle requirements for a sustainable system includes the maintenance of soil health, an increase in the rain water use efficiency of the system, increased use of fertilizer and the prevention of erosion. The maintenance of crop residues on the surface is paramount for meeting these requirements, and the competing use of crop residues must be met from other sources. These requirements can be met within a zonal tillage system combined with suitable agroforestry, which will reduce the need for crop residues. It is, however, essential that farmers participate in the development of any new technologies to ensure adoption of the new system. (C) 2001 Elsevier Science B.V. All rights reserved.