Optimal design for model discrimination and parameter estimation for itraconazole population pharmacokinetics in cystic fibrosis patients

Optimal sampling times are found for a study in which one of the primary purposes is to develop a model of the pharmacokinetics of itraconazole in patients with cystic fibrosis for both capsule and solution doses. The optimal design is expected to produce reliable estimates of population parameters for two different structural PK models. Data collected at these sampling times are also expected to provide the researchers with sufficient information to reasonably discriminate between the two competing structural models.

Adiponectin and its receptors in patients with chronic hepatitis C

Background/Aims: There is increasing interest in the influence of excess body weight and associated metabolic factors on the liver. In patients with non-alcoholic steatohepatitis, lower levels of adiponectin were associated with higher grades of hepatic steatosis and necroinflammatory activity, suggesting a pathophysiological role for this adipokine in liver disease. Methods: We studied 194 consecutive patients with untreated chronic HCV, to assess the relationship between adiponectin and its receptors and hepatic steatosis, fibrosis and inflammation. Results: Significant negative correlations between serum adiponectin and male gender, body mass index and serum insulin were observed. However, there was no association between serum adiponectin and stage of fibrosis and lower levels of serum adiponectin were associated with the presence of steatosis in males only. In contrast, there was a significant increase in serum adiponectin and hepatic adiponectin immunoreactivity with increasing inflammation. The hepatic mRNA expression of the adiponectin receptors, AdipoR1 and AdipoR2, displayed significant but opposite associations with phosphoenolpyruvate carboxykinase (PEPCK) gene expression, a substitute marker of hepatic insulin sensitivity. Conclusions: In patients with chronic HCV, adiponectin was associated with steatosis only in males and was paradoxically increased with inflammation. Our results suggest that the role of adiponectin in chronic liver diseases may be linked to gender and etiology. (c) 2005 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Telemedicine for rural and remote child and youth mental health services

The E-Child and Youth Mental Health Service was designed to provide children and adolescents in Queensland with access to specialist mental health consultations using telemedicine. A project officer provided a single point of contact for referral management and clinic coordination, thereby reducing barriers of access to the service. Over a six-month period from November 2004, 42 point-to-point videoconferences were conducted to nine sites in Queensland. Three multipoint conferences were also conducted. Eleven videoconferences (24%) were arranged for administrative purposes, and 34 (76%) were conducted for the delivery of clinical services (30 patients). The referral and consultation activity suggests an improvement in the capacity of rural and remote mental health service providers to deliver specialist services for children and adolescents.

Environmental contamination of arsenic and its toxicological impact on humans

Inorganic arsenic compounds are known carcinogens. The human epidemiologic evidence of arsenic-induced skin, lung, and bladder cancers is strong. However, the evidence of arsenic carcinogenicity in animals is very limited. Lack of a suitable animal model until recent years has inhibited studies of the mechanism of arsenic carcinogenesis. The toxicity and bioavailability of arsenic depend on its solubility and chemical forms. Therefore, it is critical to be able to measure arsenic speciation accurately and reliably. However, speciation of arsenic in more complex matrices remains a real challenge. There are tens of millions of people who are being exposed to excessive levels of arsenic in the drinking water alone. The source of contamination is mainly of natural origin and the mass poisoning is occurring worldwide, particularly in developing countries. Chronic arsenicosis resulting in cancer and non-cancer diseases will impact significantly on the public health systems in their respective countries. Effective watershed management and remediation technologies in addition to medical treatment are urgently needed in order to avoid what has been regarded as the largest calamity of chemical poisoning in the world.

Preliminary evaluation of the occurrence of herbicides and PAHs in the Wet Tropics region of the Great Barrier Reef, Australia, using passive samplers

The proximity of the Great Barrier Reef (GBR) Marine Park to areas of intensive agriculture and increasing urbanisation places the park under potential threat of contamination by land-based pollutants. Passive samplers were deployed at inshore reef and river mouth sites in the Wet Tropics region of the GBR during a dry and a wet season to measure levels of land-based organic pollutants in this environment. Two types of passive sampling devices were deployed: (i) a polar sampler, which can be used to monitor polar herbicides and (ii) semipermeable membrane devices (SPMDs) which sequester more hydrophobic compounds (e.g. PAHs, chlorpyrifos). Herbicides (diuron, simazine, atrazine, hexazinone and/or flumeturon) were detected at low concentrations (ng L-1) at all sites sampled and in both seasons. Chlorpyrifos was not detected while PAHs were present in SPMDs at levels below limits of detection. The results show that the GBR environment does contain low levels of organic pollutants and that passive sampling provides a sensitive monitoring tool for measuring waterborne organic pollutants. (c) 2005 Elsevier Ltd. All rights reserved.

Relationships of tacrolimus pharmacokinetic measures and adverse outcomes in stable adult liver transplant recipients

Alternative measures to trough concentrations [non-trough concentrations and limited area under the concentration-time curve (AUC)] have been shown to better predict tacrolimus AUC. The aim of this study was to determine if these are also better predictors of adverse outcomes in long term liver transplant recipients. The associations between tacrolimus trough concentrations (C-0), non-trough concentrations (C-1, C-2, C-4, C-6/8), and AUC(0-12) and the occurrence of hypertension, hyperkalaemia, hyperglycaemia and nephrotoxicity were assessed in 34 clinically stable liver transplant patients. The most common adverse outcome was hypertension, prevalence of 36%. Hyperkalaemia and hyperglycaemia had a prevalence of 21% and 13%, respectively. A sequential population pharmacokinetic/pharmacodynamic approach was implemented. No significant association between predicted C-0, C-1, C-2, C-4, C-6/8 or AUC(0-12) and adverse effects could be found. Tacrolimus concentrations and AUC measures were in the same range in patients with and without adverse effects. Measures reported to provide benefit, preventing graft rejection and minimizing acute adverse effects in the early post-transplant period, were not able to predict adverse effects in stable adult liver recipients whose trough concentrations were maintained in the notional target range.

Herbicide contamination and the potential impact to seagrass meadows in Hervey Bay, Queensland, Australia

Low concentrations of herbicides (up to 70 ng 1(-1)), chiefly diuron (up to 50 ng 1 (-1)) were detected in surface waters associated with inter-tidal seagrass meadows of Zostera muelleri in Hervey Bay, south-cast Queensland, Australia. Diuron and atrazine (up to 1. 1 ng g(-1) dry weight of sediment) were detected in the sediments of these seagrass meadows. Concentration of the herbicides diuron, simazine and atrazine increased in surface waters associated with seagrass meadows during moderate river flow events indicating herbicides were washed from the catchment to the marine environment. Maximum herbicide concentration (sum of eight herbicides) in the Mary River during a moderate river flow event was 4260 ng 1(-1). No photosynthetic stress was detected in seagrass in this study during low river flow. However, with moderate river flow events, nearshore seagrasses are at risk of being exposed to concentrations of herbicides that are known to inhibit photosynthesis. (c) 2004 Elsevier Ltd. All rights reserved.