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Biomedical subjects

Elaine Ferguson

Publications and source records attributed to Elaine Ferguson.

6 recordsLinked to original sources

Comparison of two indinavir/ritonavir regimens in the treatment of HIV-infected individuals.

BACKGROUND: Pharmacokinetic enhancement of protease inhibitors (PIs) with low-dose ritonavir (RTV) for salvage therapy is increasingly common. The purpose of this study was to compare the pharmacokinetics, safety, and tolerability of indinavir (IDV)/RTV at 800/200 mg (arm A) and 400/400 mg (arm B) administered twice daily in HIV-infected subjects failing their first PI-based regimen. METHODS: A phase I/II, randomized, open-label, 24-week study was conducted. Formal 12-hour pharmacokinetic evaluations were performed, and study visits occurred at baseline; at weeks 1, 2, and 4; and every 4 week thereafter for 24 weeks. Clinical symptoms and laboratory assessments were collected. Subjects were allowed to switch arms because of toxicity. RESULTS: Forty-four subjects were enrolled (22 per arm). IDV predose concentration, maximum plasma concentration and area under the curve were significantly higher in arm A. Fifty-five percent and 45% of subjects in arms A and B responded (<200 copies/mL at week 24; P = 0.76), respectively. CD4 cell responses were similar. All subjects had IDV-sensitive virus at baseline and at virologic failure. Tolerability was comparable, but all grade 3 or higher triglyceride increases occurred in arm B and more subjects in arm B switched because of toxicity (5 vs. 1 triglyceride increases). CONCLUSIONS: This is the largest formal pharmacokinetic evaluation of 2 dosage combinations of IDV/RTV in HIV-infected individuals. Pharmacokinetic parameters were consistent with previous results in patients but lower than in seronegative controls. Both regimens exhibited similar tolerability and response rates. High toxicity with a low response suggests that the optimum IDV/RTV combination would include an RTV dose <400 mg and an IDV dose <800 mg in this population.

Adolescent↗

Changes in the human mitochondrial genome after treatment of malignant disease.

Mitochondrial DNA (mtDNA) is the only extrachromosomal DNA in human cells. The mitochondrial genome encodes essential information for the synthesis of the mitochondrial respiratory chain. Inherited defects of this genome are an important cause of human disease. In addition, the mitochondrial genome seems to be particularly prone to DNA damage and acquired mutations may have a role in ageing, cancer and neurodegeneration. We wished to determine if radiotherapy and chemotherapy used in the treatment of cancer could induce changes in the mitochondrial genome. Such changes would be an important genetic marker of DNA damage and may explain some of the adverse effects of treatment. We studied samples from patients who had received radiotherapy and chemotherapy for point mutations within the mtDNA control region, and for large-scale deletions. In blood samples from patients, we found a significantly increased number of point mutations compared to the control subjects. In muscle biopsies from 7 of 8 patients whom had received whole body irradiation as well as chemotherapy, the level of a specific mtDNA deletion was significantly greater than in control subjects. Our studies have shown that in patients who have been treated for cancer there is an increased level of mtDNA damage.

Adolescent↗

Do economic constraints encourage the selection of energy dense diets?

Economic constraints, by inducing the selection of low cost energy dense diets, could indirectly be responsible for the high prevalence of obesity in low socio-economic status groups. Diet optimisation by linear programming was used to test this hypothesis, by examining the relationship between the cost and the energy density (ED) of modelled diets. Models were developed that minimized the departure from the mean adult French diet estimated from a cross-sectional dietary survey. Palatability constraints were introduced into all models. The impacts of cost on ED and of ED on cost were explored by introducing and strengthening first a constraint on cost and then a constraint on ED. Forcing the cost of the linear programming diets to decrease induced a strong increase in their EDs. In contrast, forcing the ED to increase induced only a moderate decrease in diet costs. These results suggest that, although an energy dense diet can be selected at a relatively high cost, when cost is not influencing food choices, an energy dense diet will be preferentially selected to maintain habitual French dietary patterns when the budget for food is low. This supports the hypothesis that economic constraints play a role in the high prevalence of obesity in low-income people.

Adult↗

Linear programming: a mathematical tool for analyzing and optimizing children's diets during the complementary feeding period.

During the complementary feeding period, children require a nutrient-dense diet to meet their high nutritional requirements. International interest exists in the promotion of affordable, nutritionally adequate complementary feeding diets based on locally available foods. In this context, two questions are often asked: 1) is it possible to design a diet suitable for the complementary feeding period using locally available food? and 2) if this is possible, what is the lowest-cost, nutritionally adequate diet available? These questions are usually answered using a "trial and error" approach. However, a more efficient and rigorous technique, based on linear programming, is also available. It has become more readily accessible with the advent of powerful personal computers. The purpose of this review, therefore, is to inform pediatricians and public health professionals about this tool. In this review, the basic principles of linear programming are briefly examined and some practical applications for formulating sound food-based nutritional recommendations in different contexts are explained. This review should facilitate the adoption of this technique by international health professionals.

Diet↗

Linear and nonlinear programming to optimize the nutrient density of a population's diet: an example based on diets of preschool children in rural Malawi.

BACKGROUND: Food consumption surveys are often used to detect inadequate nutrient intakes but not to determine whether inadequate nutrient intakes are due to suboptimal use of locally available foods or to insufficient availability of nutrient-dense foods. OBJECTIVES: The objectives were to describe the use of linear programming as a method to design nutrient-adequate diets of optimal nutrient density and to identify the most stringent constraints in nutritional recommendations and food consumption patterns in a population's diet. DESIGN: This analysis was conducted with the use of food consumption data collected during 2 seasons from rural Malawian children aged 3-6 y. Linear programming was used to select diets based on local foods that satisfied a set of nutritional constraints while minimizing the total energy content of the diet. Additional constraints on daily intakes of foods and food groups were also introduced to ensure that the diets were compatible with local food patterns. The strength of the constraints was assessed by analyzing nonlinear programming sensitivity. RESULTS: In the harvest season, it was possible to satisfy nutritional recommendations with little departure from the local diet. In the nonharvest season, nutritional adequacy was impaired by the low availability of riboflavin- and zinc-rich animal or vegetable foods and by the high phytate content of other foods. CONCLUSIONS: This analysis suggests that nutrition education may help improve the diets of children in the harvest season, whereas changes in the range of available foods might be needed in the nonharvest season. Linear and nonlinear programming can be used to formulate recommendations with the use of data from local food consumption surveys.

Child↗

'Leaving a mark'.

Biopsies by various means do have a risk of seeding tumour cells into the biopsy track. Even with fine needle and trocar techniques this has been proven to occur. By excising the biopsy track at the time of surgery this risk can be reduced. With needle and trocar techniques there might be little evidence of the puncture when the time of surgery takes place. We advocate using Indian ink to mark the biopsy site.

Biopsy, Needle↗