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M Kekki

Publications and source records attributed to M Kekki.

At least 73 records · Page 4Linked to original sources

Pharmacokinetics of sulfaethidole in the rat: nonlinear multicompartment solution.

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.

Acetylation↗

The nonlinear tissue-binding character of fluoride kinetics in normal and anephric subjects. Graphical analysis of serum fluoride data from man and rabbit.

A study has been made of the fluoride kinetics in man, with a series of 5 healthy subjects and 4 patients with renal insufficiency. The fluoride metabolism was found to conform to nonlinear tissue-binding kinetics. Reanalysis of findings on the rabbit reported in the literature yielded equivalent results. The tissue-binding constants elicited - probably associated with the fluoride metabolism of bone - presented no differences between healthy subjects and uremics. Uremics had a clearly lower fractional fluoride elimination rate (K) compared with the healthy controls. A significant correlation of creatinine clearance on the K value was noted.

Adult↗

Epidemiology and dynamics of gastritis in a representative sample of an Estonin urban population.

The epidemiology and dynamics of gastritis were studied in a representative sample of an urban population of Estonia. The sample consisted of 227 subjects 15-69 years old who were examined by direct-vision endoscopic biopsy, and the data were subjected to dynamic evaluation by stochastic principles. The prevalence of antral gastritis (64%) was similar to but that of body gastritis (62%) higher than that in other population samples studied by us. Correspondingly, the prevalence of atrophic antral and body gastritis was high: 38% and 37%, respectively. The prevalence of atrophic gastritis in the antrum and body increased significantly with age. On the other hand, no sex dependence of gastritis could be demonstrated. The prevalence of gastritis mainly affecting the body (32%) was significantly higher in the present than in the other Estonian sample (19%) studied by us. Complete loss of normal body glands was found in 14 subjects, and in 8 of these the antrum was normal or only slightly altered (type A gastritis). The prevalence of gastritis mainly affecting the body increased significantly with age, whereas that of gastritis mainly affecting the antrum decreased. Dynamic evaluation disclosed two basic dynamic patterns similar to those found in other population samples: the age-specific prevalences of gastritis increased with age according to the Poisson process, and gastritis started in the antrum at a younger age, but its progression was more rapid in the body mucosa. Dynamically, the chief finding of the sample was markedly more rapid progression of the body gastritis than in other samples, which explains the high prevalence of gastritis mainly affecting the body mucosa (type A gastritis) in the present series.

Adolescent↗

Age- and sex-related behaviour of gastric acid secretion at the population level.

Pentagastrin-stimulated gastric acid output and the histology of the antral and body mucosa were examined in 72 computer-selected probands and their 365 relatives, altogether 437 cases. The frequencies of upper abdominal complaints, peptic ulcer and hiatal hernia, and blood group distribution were comparable with those of the population at large. Acid output, expressed as mmol/h, mmol/h/kg of total body weight (TBW), mmol/h/kg of lean body mass (LBM), and mmol/h/kg of fat-free body weight (FFB), correlated with the changes in the body mucosa but not with those in the antrum. Acid output was lower in females than in males when expressed as mmol/h or mmol/h TBW but not when expressed in terms of FFB, which better than LBM accounts for the variation in the gastric surface area and, in this manner, for that of the parietal cell mass. This suggests that the lower acid output in females is due to a smaller gastric surface area and correspondingly smaller parietal cell mass rather than to a lower reactivity of the cells to stimulation. Acid output decreased with increasing age in both sexes, and this was due to a concomitant increase in the incidence and severity of atrophic changes in the body mucosa. An age-related decrease in acid output was not seen in males with a normal body mucosa. In females with a normal body mucosa, however, output expressed in terms of FFB showed a significant increase with age. The reason for this increase is not clear. In males and females with superficial gastritis of the body mucosa acid output decreased with increasing age regardless of the formulation used.

Adolescent↗

Pharmacokinetics of intravenously administered bumetanide in man.

Disposition of [14C]bumetanide administered intravenously to four healthy volunteers could be described by a triexponential equation. The mean half-lives associated with each exponent were 5.9 min, 46 min, and 3.1 hr, respectively. The largest fraction of dose was eliminated during the second phase; only 17% was eliminated during the last phase. The total plasma clearance averaged 228 ml/min, with renal clearance about one-half of this value. The recovery of unchanged bumetanide in urine over 2 days was 47% of the dose, while the total recovery of radioactivity in urine averaged 82% of dose. In plasma 93% of bumetanide was bound to proteins. Thus bumetanide is rapidly eliminated by both renal and nonrenal mechanisms. The elimination kinetics resembled those described for furosemide.

Adult↗

Estimation, resolution and solvability of linear compartmental models: cholesterol metabolism in man.

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.

Body Fluid Compartments↗

Lipoprotein-lipase action determining plasma high density lipoprotein cholesterol level in adult normolipaemics.

In a series of healthy normolipaemic, adult subjects, plasma triglyceride turnover, heparin-releasable lipoprotein lipase (LPL), and plasma HDL cholesterol were determined. Strong correlations were found to exist between the fractional removal rate of plasma triglycerides (FTR) or LPL as one variable and HDL cholesterol as the other, whereas the triglyceride turnover rate (TR) did not correlate with HDL cholesterol. It is concluded that lipoprotein lipase action is largely responsible for the formation of HDL cholesterol in the blood stream.

Adult↗

Intestinal metaplasia with colonic-type sulphomucins in the gastric mucosa; its association with gastric carcinoma.

The occurrence of intestinal metaplasia with colonic-type sulphomucins: (abbreviated: s-IM or s-positive IM) in the gastric mucosa was studied in 125 patients with gastric carcinoma (GCA), 62 patients with pernicious anemia (PA), 301 and 183 first-degree relatives of GCA and PA patients, 406 outpatients and in 358 controls matched from a large population sample. The sulphomucins (s-mucins) were demonstrated histochemically in endoscopic biopsy specimens by using high iron diamine and Alcian blue (pH 1) methods. The prevalence of s-IM, especially the strongly s-positive IM, was significantly higher in GCA patients than in other series or controls of the same age group. Further, s-IM was significantly more common in PA patients and its prevalence higher in GCA relatives and outpatients than in other series or controls. The occurrence of s-IM was also age-dependent and dependent on the extent of IM. It was suggested that the occurrence of s-IM can be used as a sign of lesions that are more closely associated with GCA than IM is in general.

Adult↗

Dynamics of chronic gastritis in the remnant after partial gastrectomy for duodenal ulcer.

Morphological changes in the remnant mucosa 2-20 years after operation for duodenal ulcer (DU) were analyzed in 124 male subjects by means of stochastic mathematics. Fifty non-operated male DU patients and 168 age-matched males from a population sample served as controls. Substantially no progression of gastritis was found in the DU patients. In contrast, the operative intervention caused a rapid initial progression of gastritis, continuing after 2 years approximately at the same speed as in the population at large.

Adult↗

Progression of gastritis at a population level. Comparison of a long-term follow-up with stochastic analysis of cross-sectional data.

The applicability of the stochastic theory was tested by comparing dynamic data obtained from a cross-sectional population sample with the progression of gastritis observed during a long-term follow-up study of subjects with originally normal body mucosa or superficial gastritis. A good fit of the follow-up with the basic stochastic assumptions was observed, and the progression of gastritis during the follow-up study was similar to that obtained by the stochastic analysis of the cross-sectional data.

Adolescent↗

A model solution for intestinal absorption of warfarin. A drug with non-linear distribution pharmacokinetics in the rat.

A non-linear multicompartment model with saturation kinetics of binding to plasma and interstitial fluid proteins and with non-saturable binding to tissues has been applied to the absorption of warfarin (8 mg/kg of warfarin sodium) from the rat small intestine in situ. The absorption was best described with two pathways, one into plasma and the other instantaneously into the interstitial fluid. According to the results from the best computerized curve fitting, absorption is rapid, the apparent absorption rate constant being 0.258 min -1. At hypothetical zero time 0.253 of the dose (1.0) would be located in plasma, 0.597 in interstitial fluid 0.150 in tissues.

Animals↗

Plasma triglyceride turnover in 92 adult normolipaemic and 30 hypertriglyceridaemic subjects--the effect of age, synthesis rate and removal capacity on plasma triglyceride concentration.

Plasma triglyceride (TG) turnover measurements were carried out in 92 healthy normolipaemic and 30 hypertriglyceridaemic subjects. The analysis of the data revealed an age-dependence of the efficiency with which triglyceride particles were removed from the circulation, the elimination capacity being lower in older than in younger subjects. The population at large displayed heterogeneity with regard to maximal removal capacity, as already reported. Of the three groups into which the subjects were divided according to elimination capacity, those of lowest capacity were proportionately more numerous in the hypertriglyceridaemic than in the control series. This indicates that high synthesis rate and low elimination capacity are both involved in the development of hypertriglyceridaemia in man. The TG turnover test is thought to be useful in analyses concerning the heritability of mixed hyperlipidaemic states. A statistically significant decrease of plasma lipoprotein lipase with age was established using a matched series, thus confirming earlier observations and demonstrating that turnover tests and analyses of TG-removing enzymes are in good agreement.

Adolescent↗

Relation of plasma high-density lipoprotein cholesterol to lipoprotein-lipase activity in adipose tissue and skeletal muscle of man.

Lipoprotein-lipase activity (LPL) was measured in biopsies of adipose tissue and skeletal muscle of normal human subjects, and the results were related to concentrations of cholesterol and triglycerides in plasma lipoproteins. Adipose-tissue LPL activity was significantly higher in females than in males, whereas no sex difference was observed in skeletal-muscle LPL activity. A highly significant positive correlation was present between the plasma high density lipoprotein (HDL) cholesterol level and LPL activity in adipose tissue (r = +0.66, P less than 0.001) but not between HDL and skeletal-muscle LPL. The results suggest that the activity of LPL in adipose tissue and the rate of catabolism of triglyceride-rich lipoproteins might be one of the factors that determine the concentration of HDL in plasma and at least partly account for the known sex difference in plasma HDL level.

Adipose Tissue↗