ABSTRACT
The course of antrum and body gastritis was studied using an essentially linear multicompartmental model in pernicious anemia probands, their first-degree relatives, and controls consisting of a representative family sample of a large Finnish population. Our earlier dynamic approach showed that progression of body gastritis was virtually identical in a series followed up with biopsies and in cross-comparison analyses, indicating that cross-sectional data can be used for dynamic analyses at a population level. The collected data fitted a model which consisted of stepwise progression of body gastritis to severe atrophy, of corresponding progressive steps for antral gastritis, and of regression of the antral changes after the end-stage of the body process had been reached. In addition, acceleration of the progression of gastritis in older subjects had to be taken into account in the model construction. The main findings which characterized pernicious anemia probands and their close relatives were: (1) a rapid overall progression of body gastritis particularly after 50 years of age; (2) a very rapid progression of body atrophy in its final stages, which was unrelated to age; (3) the occurrence of juvenile severe body atrophy; and (4) the healing of antral gastritis which was most marked at the stage of superficial gastritis. These results may offer a dynamic explantation for the occurrence of severe body atrophy in association with a normal or slightly altered antral mucosa in pernicious anemia and the prepernicious anemia state.
Subject(s)
Anemia, Pernicious/genetics , Gastritis, Atrophic/diagnosis , Gastritis/diagnosis , Adult , Aged , Anemia, Pernicious/complications , Chronic Disease , Female , Gastric Mucosa/pathology , Gastritis, Atrophic/etiology , Gastritis, Atrophic/genetics , Gastritis, Atrophic/pathology , Humans , Male , Middle Aged , Models, Biological , PrognosisABSTRACT
Sulfaethidole distribution and elimination in the rat was studied over a 90-fold dose range. This experimental design produced marked nonlinearity in the binding of sulfaethidole to proteins in both interstitial fluid an plasma. Using a multicompartmental model consisting of binding of sulfaethidole to plasma and interstitial fluid proteins, sulfaethidole distribution in the body could be simulated. Urinary and biliary elimination of sulfaethidole depended on the unbound drug mass in the plasma and urine flow. The results confirm the central role of the unbound species in the distribution and elimination of drugs with marked binding to plasma proteins.
Subject(s)
Sulfathiazoles/metabolism , Acetylation , Animals , Bile/analysis , Blood Proteins/metabolism , Extracellular Space/physiology , Kinetics , Male , Models, Biological , Proteins/metabolism , Rats , Rats, Inbred Strains , Sulfathiazoles/analysis , Sulfathiazoles/urineABSTRACT
The paper presents a method to test metabolic linear multicompartment models for their mathematical solvability and their power of resolution with respect to individual parameters. The method can be seen as a means of predicting not only the model theoretical identifiability but also the expected quality of estimation before undertaking any actual serial experiments. The compartmental model of human cholesterol metabolism is taken as a demonstrative problem. The analysis shows that it is possible with tracer techniques to measure the cholesterol turnover, the cholesterol fluxes between exchangeable cholesterol pools, the cholesterol masses in individual pools, and the endogenous cholesterol synthesis in individual pools if certain conditions are met. In any complex kinetic situation, performance of a systematic model analysis is recommended before embarking on large-scale experimentation.
