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Biomedical subjects

J H Thornley

Publications and source records attributed to J H Thornley.

At least 19 recordsLinked to original sources

A simple but flexible growth function.

The functional form W(t) = Wf - (Wf - Wo) exp[-k infinite (t - T) + 2c(root of t - root of T)] where Wf, Wo, k infinite, c and T are constants, is derived as a growth equation and evaluated using commonly applied growth functions such as the Gompertz, logistic, monomolecular and Richards. Further evaluation is made with reference to sets of observations on growth in a number of animal species ranging from mice to horses. The new function provides a flexible growth equation capable of describing sigmoidal and diminishing returns behaviour. It appears adept at describing sigmoidal patterns exhibiting faster early growth and a fairly low but variable point of inflexion, and can therefore be perceived as a generalised Gompertz equation. The function also has the ability to describe a wide range of hyperbolic shapes when there is no point of inflexion. The analysis described suggests that this simple equation is a worthwhile addition to the corpus of growth functions.

Animals↗

The effects of diffusion and viscosity on ruminant faecal excretion of markers in a simple compartmental model.

Using equations obtained in a previous analysis, results are computed numerically which illustrate the effects of diffusion and viscosity on faecal excretion patterns of markers in ruminants. Results are first given for plug flow, a velocity gradient produced by viscosity, and diffusion, each mechanism operating alone. Plug flow gives a period during which no marker appears in the faeces, then a sharp increase in faeces marker concentration, followed by rapid washout. A velocity gradient gives a more gradual appearance of marker in the faeces followed by a slower washout. Diffusion alone (although not realistic for ruminant marker kinetics) can give early appearance of marker followed by slow washout. Combining diffusion with a velocity gradient produced by viscosity can give a range of behaviour, depending on the effective diffusion coefficient, D'; an approximate method is used to compute these solutions. Because plug flow with no velocity gradient plus diffusion gives results similar to convective flow with a velocity gradient plus diffusion, we believe it will not be possible to determine the main mechanisms defining marker outflow patterns from observations of marker kinetics alone, and more detailed investigations will be needed. Although estimates of quantities such as mean transit time are unaffected by detailed mechanism, the interpretations of measures such as sigmoidicity, sharpness of the faecal marker concentration v. time curve, and length and nature of the washout tail are highly dependent on mechanism.

Animals↗

A sustained outbreak of Clostridium difficile in a general hospital: persistence of a toxigenic clone in four units.

OBJECTIVE: To evaluate the endemicity and epidemiology of toxigenic Clostridium difficile in a sustained outbreak of antibiotic-associated diarrhea. SETTING: University-affiliated, 465-bed tertiary care teaching hospital with adjacent cancer clinic in Hamilton, Ontario. DESIGN: From August 8, 1991, through August 31, 1993, a total of 187 cases were investigated for epidemiologic analysis of toxigenic C difficile from stool cultures, to identify the endemic clone(s). To assess the nature of contamination, cultures of inanimate surfaces in the patient environment from the four most affected units (medical teaching, nonteaching medical, hematologic oncology, and the intensive care unit) were processed for C difficile. The 229 clinical strains and 24 environmental strains isolated were typed by numerical analysis of SDS-PAGE protein patterns. RESULTS: A majority (81%) of cases in the epidemiologic analysis were associated with a toxigenic electrophoretic (EP) type 1 C difficile that was identical to the strain first isolated from an index case that occurred 18 months before the start of this study. Culture and typing of the C difficile strains from the inanimate surfaces in the four most affected units showed that the patient environment was contaminated with the toxigenic EP type 1 organism. Six other strains that occurred infrequently among cases also were found in the environment. CONCLUSIONS: A single predominant toxigenic clone has been implicated in a sustained outbreak of antibiotic-associated diarrhea that affected elderly patients. The "endemic" clone transmitted for the 25-month study period was linked to an index case shedding a toxigenic EP type 1 strain that occurred 21 months prior to the initial outbreak on the medical teaching unit. The patient environment in the affected units was found to be contaminated with the same clone, possibly due to shedding of organisms by fecally incontinent symptomatic patients. The extrinsic factors contributing to the endemic transmission of this one clone still are not well understood.

Bacterial Typing Techniques↗

On incorporating diffusion and viscosity concepts into compartmental models for analysing faecal marker excretion patterns in ruminants.

Deterministic mathematical equations are derived to describe the pattern of marker excretion in the faeces of ruminants under steady-state conditions when diffusion and viscosity concepts are introduced into a simple two-compartment scheme of the gastrointestinal tract. The basic scheme comprises a pure-mixing pool obeying first-order kinetics and a second compartment exhibiting streamline flow. Introduction of a velocity gradient, longitudinal diffusion or both into the second compartment, even with various simplifying assumptions, yields analytically insoluble equations. The impact of these mechanisms is to be investigated numerically rather than analytically in future work.

Animals↗

On the two-compartment model for estimating the rate and extent of feed degradation in the rumen.

An analysis of the compartmental scheme used to determine the rate and extent of ruminal degradation of feeds is presented. Attention is given to the kinetic representation of the degradation of the potentially degradable fraction. Changing the kinetic order of the rate, and introducing indigestible substrate inhibition and microbial activity into its representation, are investigated. This leads to response functions such as the Gompertz and logistic for describing the cumulative disappearance of potentially degradable substrate during in-sacco and in-vitro incubation.

Animals↗

Estimating the production of faeces by ruminants from faecal marker concentration curves.

The use of faecal marker concentration curves, in conjunction with compartmental analysis, is examined as a method for predicting faecal output in ruminants. Formulae for faecal production are derived for the various multicompartment models currently used to interpret marker concentration data. A comparison of observed and model-derived estimates of faecal dry matter production using three different markers is given for sheep consuming hay or a mixed diet.

Animals↗

Metabolism of the lactating cow. II. Digestive elements of a mechanistic model.

The structure and characteristics of a model suitable for estimating digestion within the rumen and rates and patterns of nutrient entry in lactating cows are presented. The model consists of 12 state variables comprising a large particle pool, small particle pools representing insoluble dietary nutrients, soluble pools representing soluble dietary nutrients, and fermentation intermediates and end products. The model was constructed assuming continuous feeding, using Michaelis-Menten or mass action kinetics. The computer program was written in ACSL to run on a VAX computer. A fourth-order Runge-Kutta procedure was used for numerical integration. Sensitivity and behavioural analysis demonstrated that overall stability and sensitivity of the model to individual parameters was generally satisfactory, but the need to improve the description and parameterization of aspects such as particle size in relation to availability, rate and affinity constants for amino acid degradation and rate constants for particle outflow from the rumen was established. Adjustments of the model to examine discontinuous feeding regimes were undertaken and initial results with respect to changes in fermentation rates, rumen acetate levels and microbial metabolism were considered realistic. Comparisons with experimental data were considered satisfactory on forage-based and medium concentrate-containing diets, but with diets comprising 90% cereal, some inconsistencies, especially with respect to predictions of volatile fatty acid production rates, were observed. Reasons for this are put forward and suggestions for improvements in the model are discussed.

Animals↗

Metabolism of the lactating cow. III. Properties of mechanistic models suitable for evaluation of energetic relationships and factors involved in the partition of nutrients.

Two models of lactating dairy cows were constructed by combining mechanistic models of digestion and metabolism reported previously and by adding elements to allow simulation of changes in tissue metabolic capacities over time. One model (day version) had an integration interval of 0.005 d and was suitable for simulation of within-day dynamics of nutrient supply and partition. The other (lactation version) had an integration interval of 1 d and was suitable for simulation of full lactation cycles. A number of simulation analyses were conducted to characterize and evaluate the models, to examine quantitative and dynamic properties of mechanisms which influence partition of nutrients, to identify aspects requiring further study, and to illustrate the potential usefulness of mechanistic, as compared to empirical, models in analyses of energy balance in lactating dairy cows.

Animal Nutritional Physiological Phenomena↗

Simulation of the metabolism of absorbed energy-yielding nutrients in young sheep: efficiency of utilization of acetate.

A previously described mathematical model that simulates the metabolism of absorbed nutrients was used to examine factors influencing the efficiency of utilization of acetate in a sheep weighing 25 kg. A significant component of the model was a function representing substrate cycles that degraded ATP when its concentration reached twice initial levels. Acetate utilization was simulated when up to 2 g mol/d were added to four diets (representing forages and concentrates) that supplied varying proportions of absorbed volatile fatty acids, glucose and protein. The basal diets provided either 4.375 (near energy balance) or 8.75 MJ/d absorbed energy. The predicted net efficiency of utilization (kf) of the energy in added acetate was high (0.58-0.70) for all combinations of absorbed nutrients at the low level of energy absorption, whereas at the higher level, it ranged from 0.16 (forage) to 0.49 (high protein concentrate). Low kf values were always associated with a considerable flux of ATP through the degradation pathway. The increase in ATP concentration that caused this pathway to operate was linked to an inhibition in the utilization of acetyl-CoA for fatty acid synthesis and an increase in its oxidation. The simulated addition of exogenous NADPH or its precursors (particularly glucose and propionate) to these diets repartitioned acetyl-CoA flux towards fatty acid synthesis instead of oxidation, decreased the flux of ATP through the degradation pathway and increased the kf of added acetate. Although a negative relationship was predicted between kf of added acetate and NADPH production for diets with increasing protein content, kf still depended on ATP flux through the degradation pathway. Addition of glucose to the high protein diets decreased this flux by decreasing acetyl-CoA oxidation and increasing fatty acid synthesis. The predictions suggest that the efficiency of acetate utilization in ruminants may be influenced by NADPH availability when a considerable amount of absorbed energy is derived from acetate. Increased absorption of glucose or propionate enhanced NADPH production, but the major effect on acetate utilization of increasing dietary protein was not through NADPH production.

Absorption↗

Simulation of the metabolism of absorbed energy-yielding nutrients in young sheep: efficiency of utilization of lipid and amino acid.

A previously described mathematical model that simulates the metabolism of absorbed nutrients in a sheep weighing 25 kg was used to examine the effects of altering lipid and amino acid absorption, and the potential of the animal to deposit protein on the efficiency of utilization (kf) of metabolizable energy. The predicted kf of energy from lipid added to several diets ranged from 0.65 to 0.74 and was influenced by both the protein and glucose content of the diet. The highest efficiency occurred when body protein deposition was limited by amino acid absorption. Lower values occurred with high protein diets when the proportion of body energy deposited as fat declined and, with low protein diets, when NADPH supply limited the synthesis of fatty acids from acetyl-CoA. Predicted kf of energy from amino acid added to several diets ranged from 0.003 to 0.47. Low values occurred when protein synthesis was limited by amino acid absorption; an increase in amino acid supply increased ATP utilization for protein synthesis and substantially reduced fat deposition with little resulting change in energy retention. The higher values occurred when most of the additional amino acid was oxidized. Glucose supply increased the kf of added amino acid primarily by reducing the synthesis of glucose from amino acids. Predicted kf of a whole diet generally declined as the proportion of protein in the diet increased. However, when the balance of absorbed nutrients was such that fat synthesis was limited by the supply of NADPH, kf increased with increasing dietary protein. Predicted kf of a diet also declined when the proportion of body energy deposited as protein increased, except when fat synthesis was limited by the supply of NADPH. The predictions suggest that kf is determined primarily by the energetic efficiency of biochemical reactions for maintenance and growth. However, most kf values less than 0.5 were associated with a flux of more than 1 g mol/d of ATP through the degradation pathway (representing substrate cycles) that occurred when NADPH supply limited the synthesis of fatty acids from acetyl-CoA.

Absorption↗

Laboratory and clinical evaluation of isolation media for Campylobacter jejuni.

Six selective isolation media were evaluated for their ability to support the growth of Campylobacter jejuni. Colony counts of 70 isolated strains of C. jejuni and recovery studies on these strains in simulated positive feces samples demonstrated that Bolton and Hutchinson' charcoal, cefoperazone, deoxycholate agar and Karmali's charcoal-based selective medium produced the highest recovery rates with the greatest suppression of other fecal flora. C. jejuni colonies were more easily recognized on charcoal-based selective medium. A clinical evaluation performed on 2,780 human, animal, and avian feces specimens confirmed the results of the laboratory investigation. From human samples, 4 more strains of C. jejuni were isolated on charcoal-based selective medium than were isolated on Skirrow medium, and 19 more strains of C. jejuni or C. coli were isolated on charcoal-based selective medium from animal specimens. Suppression of normal fecal flora was also greater on charcoal-based selective medium.

Animals↗

On the mathematics of digesta flow kinetics.

A unifying mathematical analysis of the use of compartmental models with and without time lags is given, with particular reference to the use of such models for digesta movement along the gastro-intestinal tract of the ruminant. First the generalized compartmental model without time lags is developed, and then it is shown how discrete time lags may be incorporated into this formalism. The important relationship between distributed lags, especially the gamma-distributed time lags, and the equivalent compartmental scheme, is emphasized. It is shown how distributed time lags can be included in a general compartmental model. The treatment covers, as special cases, some widely used models, and shows their relationship to each other and to other possible models. Finally a compartmental interpretation is outlined for a recently proposed double-exponential model.

Animals↗

Simulation of the metabolism of absorbed energy-yielding nutrients in young sheep.

A mathematical model is described, which simulates the metabolism of absorbed nutrients (amino acids, acetic acid, butyric acid, glucose, lipid and propionic acid) in growing sheep. The basic assumption of the model is that each nutrient is partitioned between synthetic, oxidative or intermediate reactions with rates of reaction which are described using enzyme kinetics. These rates depend on the relationship between maximum reaction rates, constants of affinity and inhibition and the concentrations of metabolites as determined by the model. Synthetic reactions calculate fat and protein deposition while intermediate reactions involve the production of ATP and NADPH. There is a total of twelve state variables and the model, programmed in CSMP and ACSL, is solved by integration of twelve differential equations. The model calculates the efficiency of utilization of metabolizable energy for different nutrient inputs and the results may be interpreted in terms of fluxes through the metabolite pools. Simulations using inputs representing forage- and concentrate-based diets indicated decreased efficiency for the forage at high levels of intake and possible reasons for this were further studied in simulations where the inputs of protein and glucose were varied.

Acetates↗

Rapid identification of antibiotic-resistant corynebacteria with the API 20S system.

The API 20S system (Analytab Products, Plainview, N.Y.) was evaluated for the rapid identification of multiply antibiotic-resistant aerobic diphtheroids. Sixty-eight clinical isolates of multiply resistant Centers for Disease Control group JK and group D2 corynebacteria had API 20S profiles which were clearly different from those of a number of strains of other Corynebacterium species which were tested. The API 20S system allowed more rapid identification of antibiotic-resistant diphtheroids than conventional biochemical tests. Its use for corynebacteria other than group JK and group D2 is not recommended at this time.

Anti-Bacterial Agents↗

Laboratory and clinical evaluation of modified New York City medium (Henderson formulation) for the isolation of Neisseria gonorrhoeae.

The growth-promoting properties of several ingredients of New York City (NYC) medium were investigated by using 100 recently isolated clinical strains of Neisseria gonorrhoeae. Difco GC medium base promoted the growth of large colonies of gonococci significantly better than other commercial GC medium bases. A 1% agar concentration resulted in the growth of larger colonies than 2% agar, without affecting the stability of the gel. Neither replacement of horse plasma with horse serum nor reducing the concentration of added serum from 12 to 3% affected the growth of even the most fastidious strains tested. From these observations, a modified NYC medium (Henderson) has been formulated which is easy to prepare and less expensive than NYC or Thayer-Martin medium. In a direct clinical comparison with 1,275 specimens, an isolation rate of 6.5% was achieved with both NYC medium and the Henderson formulation.

Culture Media↗

Criteria for detection of Clostridium difficile toxin production by counterimmunoelectrophoresis.

Counterimmunoelectrophoresis (CIE) was compared with a cytotoxicity assay and isolation of toxin-producing Clostridium difficile for the diagnosis of antibiotic-associated diarrhea. Standardized criteria for CIE positivity were established as two major precipitin lines with specific C. difficile antitoxin. Using these criteria on 425 fecal specimens, we determined the sensitivity of CIE (80%) to be comparable to that of the cytotoxicity assay (82%). Both methods were highly specific. With carefully controlled techniques, CIE can be used in routine diagnostic laboratories to screen for toxigenic C. difficile.

Animals↗

A human coenurus infection in Canada.

This is the first description of human coenurus infection in Canada. The patient, a 38-year-old Caucasian woman, suffered severe and incapacitating symptoms, including recurrent rash, pyrexia, night sweats and lymphadenopathy, that were suspicious of a lymphoma, possibly Hodgkin's disease. She received several trials of chemotherapy over a 3-year period which controlled her symptoms, but only during the treatment periods. The appearance of a hemorrhagic mass in the left breast led to the surgical removal of bladder-like cysts. The patient's symptoms have not recurred since the cysts were exercised. These have been identified as larvae of Taenia serialis.

Adult↗