Positive reform of tuna farm diving in South Australia in response to government intervention

© 2001 by Occupational and Environmental MedicineObjectives: Much of the tuna harvested in South Australia since 1990 has involved "farming" techniques requiring the use of divers. From 1993 to 1995, 17 divers from this industry were treated for decompression illness (DCI). In response, the State Government introduced corrective strategies. A decrease in the number of divers presenting for treatment was subsequently recorded. Consequently, the hypothesis was tested that the government intervention resulted in a decrease in the incidence of DCI in the industry and an improved clinical outcome of divers with DCI. Methods: The incidence of treated DCI in tuna farm divers was estimated from the number of divers with DCI treated and the number of dives undertaken extrapolated from a survey of the industry in 1997-8. General health was measured in the tuna farm diving population by a valid and reliable self assessment questionnaire. The outcome of the divers treated for DCI was analysed with a modified clinical severity scoring system. Results: The apparent incidence of treated DCI has decreased in tuna farm divers since the government intervention. The evidence supports a truly decreased incidence rather than underreporting. The general health of the tuna farm divers was skewed towards the asymptomatic end of the range, although health scores indicative of DCI were reported after 1.7% of the dives that did not result in recognised DCI. The clinical outcome of the divers treated since the intervention has improved, possibly because of earlier recognition of the disease and hence less time spent diving while having DCI. Conclusions: The government intervention in the tuna industry in South Australia has resulted in a reduced incidence of DCI in the industry

PKQuest: capillary permeability limitation and plasma protein binding – application to human inulin, dicloxacillin and ceftriaxone pharmacokinetics

BACKGROUND: It is generally assumed that the tissue exchange of antibiotics is flow limited (complete equilibration between the capillary and the tissue water). This assumption may not be valid if there is a large amount of plasma protein binding because the effective capillary permeability depends on the product of the intrinsic capillary permeability (PS) and the fraction of solute that is free in the blood (fw(B)). PKQuest, a new generic physiologically based pharmacokinetic software routine (PBPK), provides a novel approach to modeling capillary permeability in which the only adjustable parameter is the PS of muscle. METHODS: All the results were obtained by applying PKQuest to previously published human pharmacokinetic data. RESULTS: The PKQuest analysis suggests that the highly protein bound antibiotics dicloxacillin and ceftriaxone have a significant capillary permeability limitation. The human muscle capillary PS of inulin, dicloxacillin and ceftriaxone was 0.6, 13 and 6 ml/min/100 gm, respectively. The ceftriaxone protein binding is non-linear, saturating at high plasma concentrations. The experimental ceftriaxone data over a wide range of intravenous inputs (0.15 to 3 gms) was well described by PKQuest. PKQuest is the first PBPK that includes both permeability limitation and non-linear binding. CONCLUSIONS: Because of their high degree of plasma protein binding, dicloxacillin and ceftriaxone appear to have a diffusion limited exchange rate between the blood and tissue and are not flow limited as had been previously assumed. PKQuest and all the examples are freely available at