The absorption and excretion of fluoride and arsenic in humans

The absorption and excretion of fluoride and arsenic were measured in a group of healthy volunteers given drinking water with naturally high concentration of fluoride (F 2.3 mg/l), or high concentration of arsenic (As 0.15 mg/l), or high concentrations of both fluoride and arsenic (F 2.25 mg/l, As 0.23 mg/l and F 4.05 mg/l, As 0.58 mg/l), respectively. The results indicated that, for arsenic, the absorption rate, the proportion of urinary excretion and the biological-half-life did not show statistically significant differences between drinking water containing high arsenic alone and drinking water containing different levels of high arsenic and fluoride. Excretion and retention of arsenic were positively correlated to the total arsenic intake. Similar results were observed for fluoride. This suggests that there are different metabolic processes for arsenic and fluoride in respect to absorption and excretion; and no joint action can be attributed by these two elements. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.

Comparison of two population pharmacokinetic programs, NONMEM and P-PHARM, for tacrolimus

Objectives: To compare the population modelling programs NONMEM and P-PHARM during investigation of the pharmacokinetics of tacrolimus in paediatric liver-transplant recipients. Methods: Population pharmacokinetic analysis was performed using NONMEM and P-PHARM on retrospective data from 35 paediatric liver-transplant patients receiving tacrolimus therapy. The same data were presented to both programs. Maximum likelihood estimates were sought for apparent clearance (CL/F) and apparent volume of distribution (V/F). Covariates screened for influence on these parameters were weight, age, gender, post-operative day, days of tacrolimus therapy, transplant type, biliary reconstructive procedure, liver function tests, creatinine clearance, haematocrit, corticosteroid dose, and potential interacting drugs. Results: A satisfactory model was developed in both programs with a single categorical covariate - transplant type - providing stable parameter estimates and small, normally distributed (weighted) residuals. In NONMEM, the continuous covariates - age and liver function tests - improved modelling further. Mean parameter estimates were CL/F (whole liver) = 16.3 1/h, CL/F (cut-down liver) = 8.5 1/h and V/F = 565 1 in NONMEM, and CL/F = 8.3 1/h and V/F = 155 1 in P-PHARM. Individual Bayesian parameter estimates were CL/F (whole liver) = 17.9 +/- 8.8 1/h, CL/F (cutdown liver) = 11.6 +/- 18.8 1/h and V/F = 712 792 1 in NONMEM, and CL/F (whole liver) = 12.8 +/- 3.5 1/h, CL/F (cut-down liver) = 8.2 +/- 3.4 1/h and V/F = 221 1641 in P-PHARM. Marked interindividual kinetic variability (38-108%) and residual random error (approximately 3 ng/ml) were observed. P-PHARM was more user friendly and readily provided informative graphical presentation of results. NONMEM allowed a wider choice of errors for statistical modelling and coped better with complex covariate data sets. Conclusion: Results from parametric modelling programs can vary due to different algorithms employed to estimate parameters, alternative methods of covariate analysis and variations and limitations in the software itself.

Comparison of an ELISA and an LC/MS/MS method for measuring tacrolimus concentrations and making dosage decisions in transplant recipients

This study compared an enzyme-linked immunosorbent assay (ELISA) to a liquid chromatography-tandem mass spectrometry (LC/MS/MS) technique for measurement of tacrolimus concentrations in adult kidney and liver transplant recipients, and investigated how assay choice influenced pharmacokinetic parameter estimates and drug dosage decisions. Tacrolimus concentrations measured by both ELISA and LC/MS/MS from 29 kidney (n = 98 samples) and 27 liver (n = 97 samples) transplant recipients were used to evaluate the performance of these methods in the clinical setting. Tacrolimus concentrations measured by the two techniques were compared via regression analysis. Population pharmacokinetic models were developed independently using ELISA and LC/MS/MS data from 76 kidney recipients. Derived kinetic parameters were used to formulate typical dosing regimens for concentration targeting. Dosage recommendations for the two assays were compared. The relation between LC/MS/MS and ELISA measurements was best described by the regression equation ELISA = 1.02 . (LC/MS/MS) + 0.14 in kidney recipients, and ELISA = 1.12 . (LC/MS/MS) - 0.87 in liver recipients. ELISA displayed less accuracy than LC/MS/MS at lower tacrolimus concentrations. Population pharmacokinetic models based on ELISA and LC/MS/MS data were similar with residual random errors of 4.1 ng/mL and 3.7 ng/mL, respectively. Assay choice gave rise to dosage prediction differences ranging from 0% to 30%. ELISA measurements of tacrolimus are not automatically interchangeable with LC/MS/MS values. Assay differences were greatest in adult liver recipients, probably reflecting periods of liver dysfunction and impaired biliary secretion of metabolites. While the majority of data collected in this study suggested assay differences in adult kidney recipients were minimal, findings of ELISA dosage underpredictions of up to 25% in the long term must be investigated further.

Factors affecting cane yield and commercial cane sugar in the Tully district

The Tully Sugar Mill has collected information about sugarcane supplied for crushing from every block in the mill district from 1970 to 1999. Data from 1988 to 1999 were analysed to understand the extent of the variation in cane yield per hectare and commercial cane sugar in the Tully mill area. The key factors influencing the variation in cane yield and commercial cane sugar in this commercial environment were identified and the variance components computed using a restricted maximum likelihood methodology. Cane yield was predominantly influenced by the year in which it was harvested, the month when the crop was ratooned (month of harvest in the previous year) and the farm of origin. These variables were relatively more important than variety, age of crop or crop class (plant crop, first ratoon through to fourth or older ratoons) and fallowing practice (fallow or ploughout-replant). The month-of-ratooning effect was relatively stable from year-to-year. Commercial cane sugar was influenced by the year of harvest, the month of harvest and their interaction, in that the influence of the month of harvest varied from year to year. Variety and farm differences were also significant but accounted for a much lower portion of the variation in commercial cane sugar. An empirical model was constructed from the key factors that influenced commercial cane sugar and cane yield to quantify their combined influence on sugar yield (t/ha). This may be used to assist mill personnel to predict their activities more accurately, for example to calculate the impact of a late finish to the current harvest season on the following year's crop.

Structural ordering of coal char during heat treatment and its impact on reactivity

The effect of heat treatment on the structure of an Australian semi-anthracite char was studied in detail in the 850-1150degreesC temperature range using XRD, HRTEM, and electrical resistivity techniques. It was found that the carbon crystallite size in the char does not change significantly during heat treatment in the temperature range studied, for both the raw coal and its ash-free derivative obtained by acid treatment. However, the fraction of the organized carbon in the raw coal chars, determined by XRD, increased with increase of heat treatment time and temperature, while that for the ash-free coal chars remained almost unchanged. This suggests the occurrence of catalytic ordering during heat treatment, supported by the observation that the electrical resistivity of the raw coal chars decreased with heat treatment, while that of the ash-free coal chars did not vary significantly. Further confirmatory evidence was provided by high resolution transmission electron micrographs depicting well-organized carbon layers surrounding iron particles. It is also found that the fraction of organized carbon does not reach unity, but attains an apparent equilibrium value that increases with increase in temperature, providing an apparent heat of ordering of 71.7 kJ mol(-1) in the temperature range studied. Good temperature-independent correlation was found between the electrical resistivity and the organized carbon fraction, indicating that electrical resistivity is indeed structure sensitive. Good correlation was also found between the electrical resistivity and the reactivity of coal char. All these results strongly suggest that the thermal deactivation is the result of a crystallite-perfecting process, which is effectively catalyzed by the inorganic matter in the coal char. Based on kinetic interpretation of the data it is concluded that the process is diffusion controlled, most likely involving transport of iron in the inter-crystallite nanospaces in the temperature range studied. The activation energy of this transport process is found to be very low, at about 11.8 kJ mol(-1), which is corroborated by model-free correlation of the temporal variation of organized carbon fraction as well as electrical resistivity data using the superposition method, and is suggestive of surface transport of iron. (C) 2002 Elsevier Science Ltd. All rights reserved.

Some new killing trick: Welfare reform and drug markets in a U.S. urban ghetto

Ethnographic data collected over a 5-year period is analyzed to determine how the Personal Responsibility & Work Opportunity Reconciliation Act of 1996 (PRWORA) has affected the lives of young male drug dealers from AIDS-afflicted families residing in Detroit. The data analysis indicated that the participants perceived drug dealing as the only viable employment opportunity for meeting the quotidian & health care needs of their families. The findings also revealed that the participants were highly aware of local political processes & the necessities of caring for relatives living with AIDS. Additional attention is dedicated to exploring the state of MI's rationale for ending the General Assistance Program, the sociocultural foundations of the PRWORA, various stipulations of the PRWORA, & how the PRWORA has augmented the legal vulnerability of welfare recipients. It is concluded that the PRWORA will force many welfare recipients to engage in illicit activities & will generally decrease recipients' health. 59 References. J. W. Parker

Associations between human liver and kidney cadmium content and immunochemically detected CYP4A11 apoprotein

This present study was undertaken to assess potential effects of cadmium on CYP4A11 apoprotein in human liver and kidney as detected by Western blotting using a highly specific anti-peptide antibody. Liver and kidney cortex samples were autopsy specimens of 37 individuals (26 mates and I I females) whose ages ranged from 3 to 89 years. All were Caucasians who had not been exposed to cadmium in the workplace. Reduced CYP4A11 apoprotein levels were found in chronic hepatitis samples and in liver samples showing fatty changes. In contrast, increased CYP4A11 apoprotein levels were found in liver samples having higher cadmium content compared to the lower cadmium content samples. Increased CYP4A11 levels were also found in liver samples from female donors, compared to male donors; the difference being attributable to higher female liver cadmium burden. In distinction to liver, lowered CYP4A11 levels were seen in the kidney cortex samples which have high cadmium content, It is proposed here that the difference between the absolute cadmium burden of the liver and kidney samples may be responsible for the different patterns of expression of CYP4A11 in these two tissues. Further, since cadmium exposure may be associated with derangement in blood pressure control, it is interesting to note the possible relationship between altered CYP4A11-dependent production of arachidonic acid hydroxy and epoxy metabolites in kidney cortex and altered control of blood pressure. Our findings provide a possible link between these observations. (C) 2002 Elsevier Science Inc. All rights reserved.

Confined-unconfined flow in a horizontal confined aquifer

Mixed confined and unconfined groundwater flow occurs in a bounded initially dry aquifer when the hydraulic head at the side boundary suddenly rises above the elevation of the aquifer's top boundary. The flow problem as modelled by the Boussinesq equation is non-trivial because of the involvement of two moving boundaries. The transformed equation (based on a similarity transformation) can, however, be dealt with more easily. Here, we present an approximate analytical solution for this flow problem. The approximate solution is compared with an 'exact' numerical solution and found to be a very accurate description for describing the mixed confined and unconfined flow in the confined aquifer. (C) 2002 Elsevier Science B.V. All rights reserved.

Telemedicine for new neurological outpatients: putting a randomized controlled trial in the context of everyday practice

In a retrospective review, the telemedical management of 65 outpatients from a randomized controlled trial (RCT) of telemedicine for non-urgent referrals to a consultant neurologist was compared with the management of 76 patients seen face to face in the same trial, with that of 150 outpatients seen in the neurology clinics of district general hospitals and with that of 102 neurological outpatients seen by general physicians. Outcome measures were the numbers of investigations and of patient reviews. The telemedicine group did not differ significantly from the 150 patients seen face to face by neurologists in hospital clinics in terms of either the number of investigations or the number of reviews they received. Patients from the RCT seen face to face had significantly fewer investigations but a similar number of reviews to the other 150 patients seen face to face by neurologists (the disparity in the number of investigations may explain the negative result for telemedicine in that RCT). Patients with neurological symptoms assessed by general physicians had significantly more investigations and were reviewed significantly more often than all the other groups. Patients from the RCT seen by telemedicine were not managed significantly differently from those seen face to face by neurologists in hospital clinics but had significantly fewer investigations and follow-ups than those patients managed by general physicians. The results suggest that management of new neurological outpatients by neurologists using telemedicine is similar to that by neurologists using a face-to-face consultation, and is more efficient than management by general physicians.

A review of guidelines and standards for telemedicine

We conducted a review to establish the range and scope of current telemedicine guidelines and standards. Published guidelines were identified by searching the Medline and Telemedicine Information Exchange (TIE) databases, and by performing a Google search using the term 'telemedicine guidelines'. Three types of guidelines were identified, namely clinical, operational and technical. Clinical guidelines included those for teleradiology, telepsychiatry, home telenursing, minor injuries telemedicine, surgical telemedicine, teledermatology and telepathology. Operational guidelines included those for email communication, Internet access and videoconferencing. Technical guidelines included those from the American Telemedicine Association and the US Office for the Advancement of Telehealth. The main standards relevant to telemedicine include those of the International Telecommunication Union and the DICOM standard. The scarcity of guidelines and standards suggests that telemedicine is not yet near to routine use. If an international telemedicine organization were to take responsibility for defining guidelines, under the direction of clinicians with appropriate telemedicine experience, this might speed up their development.