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Biomedical subjects

R C Boston

Publications and source records attributed to R C Boston.

46 records · Page 3Linked to original sources
PubMed1987

Quantitation of phosphorus excretion in sheep by compartmental analysis.

The control of phosphorus excretion in sheep has been examined by constructing a kinetic model that contains a mechanistic set of connections between blood and gastrointestinal tract. The model was developed using experimental data from chaff-fed sheep and gives an accurate description of the absorption and excretion of phosphorus in feces and urine of the ruminating sheep. Simulation of the response to an intravenous phosphorus infusion by adding an inflow of 2 g/day of phosphorus into the compartment describing blood, predicted values for fecal output of phosphorus lower than found experimentally. However, by alteration of the parameters describing absorption or salivation, the predictions approached experimental values. Similarly simulation of the conditions existing when a liquid diet was infused directly into the abomasum, i.e., a decrease in salivation rate [L(4.1)] and dietary phosphorus entering compartment 5 (abomasum) instead of compartment 4 (rumen), gave incorrect predictions for plasma and urinary phosphorus, but when the parameter for urinary phosphorus was increased the predicted values approached experimental values. These results indicated the main control site for phosphorus excretion in the ruminating sheep was the gastrointestinal tract, whereas for the nonruminating sheep fed the liquid diet, control was exerted by the kidney. A critical factor in the induction of adaptation of phosphorus reabsorption by the kidney was the reduction in salivation, and since this response occurred independently of marked changes in the delivery of phosphorus to the kidney, a humoral factor may be involved in this communication between salivary gland and kidney.

Animals↗
PubMed1986

The methodology of compartmental modeling as applied to the investigation of lipoprotein metabolism.

The statements to this point only give a cursory review of the beginning (20 years) of the kinetic approach to the classification of lipoproteins and subsystems which are involved in their synthesis and metabolism. At the present time the following partial list of theoretical findings expressed through model building can be made for the lipid and lipoprotein field: A cascade process of delipidation for VLDL exists and the rate of this process is decreased in subjects with hyperlipoproteinemia. ApoC recycles between VLDL and HDL in response to the dynamics of the delipidation cascade. New synthesis of apoB first appears with newly synthesized VLDL. VLDL apoB synthesis decreased in hyperlipidemic states examined. Multiple synthesis pathways exist for the triglyceride moiety of VLDL as determined by the transit time of a precursor through the conversion pathway. Thus the isotopic precursor methods now yield the same results as the more invasive techniques. Kinetic heterogeneity of VLDL, IDL, LDL, and HDL has been established. Kinetic heterogeneity for apoA-I, apoA-II, apoB, apoC-2 and apoC-3 have been established. The presence of direct pathways for IDL and LDL synthesis have been established. Irreversible loss of apoC from HDL has been predicted using models. Synthesis of apoC has been found to be invariant in hyperlipoproteinemic states studied. Hepatic cholesterol compartments associated with the formation of bile acids and biliary cholesterol derive a majority of their cholesterol from newly synthesized and lipoprotein-free cholesterol. More than 85% of the free cholesterol in the beta-lipoproteins cycles directly through the HDL. Free cholesterol recycles between HDL and tissue pools and between HDL and beta-lipoproteins.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

The maintenance, distribution and development of biomedical computer software: an exercise in software engineering.

The growing reliance of biomedical investigations on computer software in almost all facets of their work places considerable emphasis on the need for the integrated management of the software. In order to efficiently develop, distribute, and maintain the software, tools are required which not only automate these tasks but also, wherever possible, 'semi-intelligently', alert their user to irregular situation. We describe an assortment of such tools routinely used in the management of the SAAM/CONSAM biokinetic software and illustrate their application. Furthermore, using these techniques we have presented some comparative performances of numerical integrators and of computer processors.

Computers↗
PubMed1986

Metabolic consequences of prolonged hyperinsulinemia in humans. Evidence for induction of insulin insensitivity.

Hyperinsulinemia is frequently associated with a variety of insulin-resistant states and has been implicated causally in the development of insulin resistance. This study examines the metabolic consequences of prolonged hyperinsulinemia in humans. Basally and 1 h after cessation of a 20-h infusion of insulin (0.5 mU X kg-1 X min-1, aimed at elevating plasma insulin levels to approximately 30 mU/L) or normal saline, subjects were assessed for glucose turnover with 3-[3H]glucose; insulin sensitivity, as measured by either the euglycemic glucose-clamp technique or the intravenous glucose tolerance test (IVGTT) minimal model method of Bergman; and monocyte insulin-receptor binding. Hepatic glucose production (Ra) was suppressed by greater than 95% during each euglycemic clamp and during the 20-h insulin infusion. After the insulin infusion, Ra and glucose utilization rate returned to the initial basal level within 1 h, as did insulin levels. At that time, insulin sensitivity was significantly decreased, as measured by the "insulin action" parameter during the 40- to 80-min phase of the clamp (0.049 +/- 0.003 vs. 0.035 +/- 0.007 min-1, P less than .05) and during the 80- to 120-min phase (0.047 +/- 0.005 vs. 0.039 +/- 0.007 min-1, .05 less than P less than .1).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Movement of water within the body of sheep fed at maintenance under thermoneutral conditions.

Two mature Border Leicester x Merino wethers were maintained with continuous feeding under thermoneutral conditions. Their water balance was recorded for 2 weeks; at the beginning of each week they were given a dose of tritiated water (TOH) into the pulmonary artery or the rumen and samples were taken from both the pulmonary artery and the rumen. A four-compartment model was developed which simultaneously fitted the balance and tracer data. The half-time of TOH in body water was 6.7 days for one sheep and 7.6 days for the other; TOH space was about 55% of liveweight in both sheep. The bidirectional flux of water between the plasma-accessible compartment and 'bound' intracellular water averaged 45 litres per hour and that between plasma-accessible water and rumen water averaged 3.2 litres per hour. The mean residence times of a water molecule in the rumen were, for the two sheep, 60 and 63 min and the time constants for flow from the rumen were 12.3 and 13.4 h. Consideration of the rumen water balance suggested that there was net movement of water from the rumen to the plasma at about 200 ml/h; diffusion accounted for 86% of the influx to and 92% of the efflux from the rumen.

Animals↗
PubMed1983

Fetal and maternal endocrine responses to exercise in the pregnant ewe.

Maternal and fetal concentrations of plasma insulin, pancreatic glucagon, growth hormone (GH), corticosteroids and enteroglucagon, and of blood glucose and lactate, were measured in well-fed, late pregnant ewes before, during and after walking on a treadmill at 0.7 m.s-1, 10 degrees slope for 60 min. Exercise caused rapid and substantial increases in maternal concentrations of glucose, lactate, pancreatic glucagon and corticosteroids, smaller but significant decreases in levels of GH and enteroglucagon, and no change in insulin. With the exception of GH, concentrations of these maternal hormones had returned to pre-exercise levels within 20 min of stopping exercise. The exercise-induced maternal hyperglycaemia was associated with a proportionately similar, rapid increase in fetal blood glucose; fetal blood lactate and plasma corticosteroids also increased, but at slower rates and other fetal hormone concentrations were unchanged. During recovery there was a rapid increase in fetal insulin levels. The results are discussed in terms of the regulation of exercise-induced changes in maternal energy metabolism, and fetal metabolic and hormonal sensitivity to these changes.

Adrenal Cortex Hormones↗
PubMed1983

Evidence of possible dose-dependent doxorubicin plasma kinetics in man.

The published plasma clearance profiles of doxorubicin in man (with differing liver status) have been analyzed further using a kinetic model instead of a linear regression model. At high (60 mg/m2 and 45 mg/m2) and intermediate (30 mg/m2) doxorubicin dose levels, a triphasic drug clearance pattern is apparent. However, at a low dose level (15 mg/m2), a biphasic profile can adequately describe the kinetics. This association of the kinetics with drug dose has been demonstrated in several ways, the simplest of which involves graphic overlaying of juxtaposed plasma clearances, and shows the emergence of a kinetic profile for low dose levels that is markedly different from that at high dose levels. At doses greater than about 45 mg/m2, a probable saturation of response mechanisms is observed. It is not possible to interpret these results in terms of pure dose-dependent responses because of the varying health status of the individual subjects between and within experimental treatment. However, in light of our findings further investigation into the possibility of such an effect should be undertaken, particularly in view of its clinical ramifications.

Body Fluid Compartments↗
PubMed1979

Variations in the response of sheep to experimental magnesium deficiency.

Hypomagnesaemia was induced in adult sheep by changing their diet from chaff given orally to a milk diet, low in Mg, infused via the abomasum. All sheep given the milk diet developed hypomagnesaemia and four out of 19 developed nervous convulsions similar to the natural disease grass tetany. Analysis of the sequential changes in plasma Ca, P and Mg revealed a striking positive correlation between Ca and Mg and hypocalcaemia thus appeared to be a general response to Mg deficiency. Many sheep appeared to adapt to the deficiency since after a period of about 11 days the decline in plasma Mg (and Ca) was either alleviated or reversed. However the four sheep which developed convulsions all showed a rapid and substantial decline in plasma Mg associated with a decline in plasma Ca.

Animals↗
PubMedDate not supplied

Conversational SAAM--an interactive program for kinetic analysis of biological systems.

CONSAM is a conventional version of the kinetic modelling program SAAM. Adjoined to the model processing capability of SAAM, CONSAM additionally affords the user creation, inspection, and alteration capabilities in model manipulation, assessment, and development. To achieve this flexibility CONSAM incorporates a text editor, a solution-saving facility, a model image-saving facility and a graphics package. Command syntax and command logic checking together with command argument defaulting help make CONSAM easy to use. The use of CONSAM in modelling a non-linear drug response to a moderately complicated dosing strategy is presented.

Computers↗