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Biomedical subjects

U Fischer

Publications and source records attributed to U Fischer.

At least 307 records · Page 17Linked to original sources
PubMed1983

Absorption rates of subcutaneously injected insulin in the dog as calculated from the plasma insulin levels by means of a simple mathematical model.

The appearance rate of insulin (calculated insulin secretion rate) in the circulating blood after subcutaneous injection was estimated in diabetic dogs from serial measurements of immunoreactive insulin concentrations using a simple mathematical model based on the insulin half-life and the distribution space. In the case of highly purified monocomponent porcine insulin, maximum concentrations occurred after 30-60 min. The duration of insulin appearance was dose-dependent and the rate of appearance could be described by a bi-exponential function. It was linearly dose-dependent but the effect on glycaemia showed saturation kinetics. The action of the injected dose on the fasting glycaemia diminished when the appearance rate became less than 0.3 mU X kg-1 X min-1. Fractional dose recovery was between 70% and 90% and was not different between depot and regular insulin. Appearance kinetics were not significantly affected by the initial glycaemia. The model presented provides a means for quantitative characterization of different insulin preparations.

Absorption↗
PubMed1983

Glucose metabolism studied isotopically in diabetic dogs: effect of restoration of peripheral normoinsulinaemia by the artificial B cell.

Normoglycaemia, peripheral normoinsulinaemia, and normoglucagonaemia were restored acutely in chronically diabetic dogs, using an extracorporal artificial B cell with peripheral venous insulin administration. Glucose metabolism was analysed by a non-steady-state tracer technique with double-labelled glucose (6-3H- and U-14C-glucose), and the incorporation of the 14C label into plasma lactate was determined. In the basal state, glucose turnover rates were not different from those in non-diabetic controls; but recirculation of the glucose-C label through the Cori cycle, and lactate labelling from glucose utilization were decreased. The glycaemic response to an intravenous infusion of non-labelled glucose was distinctly enhanced. This was based on a reduction in the rates of glucose disappearance. Its rates of appearance (total endogenous glucose production) were, however, suppressed to a normal extent by the exogenous glucose. Accordingly carbon recycling was nearly totally suppressed during the glucose infusion as in the controls. It is concluded that metabolic recompensation in these fasting, resting diabetic dogs remained incomplete because the interval of normoinsulinaemia, which obviously applied only to the peripheral circulation, was not long enough.

Animals↗
PubMed1983

Compliance testing by measurement of piracetam in urine--a possible method of compliance control for piracetam intakers. An empirical investigation.

All teams of investigators concerned with compliance rate have come to the conclusion that one can seldom rely on patients to take their tablets as prescribed. In case of long-term medication the problem becomes even more acute. A method for checking on compliance is, therefore, of great help in controlling medical therapy as well as in judging the effectiveness of pharmaceuticals. The results of this study imply that diachronic determination of piracetam concentration in patients' urine is an especially simple way of testing compliance without undue strain on the patient.

Adult↗
PubMed1983

Drug compliance of pregeriatric rehabilitation patients. Brief communication on a longitudinal investigation.

An overview on an follow-up study is given that concerns the drug-compliance of 990 pregeriatric rehabilitation patients. During 20 days the drug intake of every patient was controlled by riboflavine method. The compliance-rate was at 47.9 +/- 32.4%, and it was relatively constant during the course of the investigation. Other features as age, nationality, number of risk factors etc. correlated but moderately though significantly with the compliance-rate. The lowest values had foreigners, and/or patients prone to nicotine or alcohol abuse. The highest rate was found on patients being in the state after heart infarction.

Humans↗
PubMed1983

Not the artificial beta cell algorithms but their parameter values are important in automated glucose control of insulin-dependent diabetes.

The blood glucose responses of diabetic dogs on the ABC are nearly identical if different algorithms, but equivalent sets of parameters are used to control the glucose-dependent insulin infusion. There are however some differences in the insulin doses applied, which obviously result from different response kinetics of the particular formula to the minor BG oscillations that always occur. In the practical application of closed-loop systems the control constants should be individually estimated on the basis of certain controlled plant characteristics. For use in patients the checking and modeling systems still have to be simplified. The limits of the study, i.e. the fact that normoglycemia was restored for a short time only using the IV instead of the physiological portal route, remain the subject of further investigation.

Animals↗
PubMed1982

Plasma insulin and glucose tolerance in pancreatectomized dogs after autologous partial pancreas transplantation. Loss of the insulinogenic reflex after oGTT and meal feeding.

A transplanted pancreas is not subjected to the influence of external innervation. It can therefore be used to study the mechanism governing the early phase of insulin secretion after oral glucose intake or meals, which is independent of any absorption causing increase in the plasma glucose level. Three totally pancreatectomized dogs had the proc. lienalis of the pancreases (35% of the total pancreas weight) transplanted autologously into the abdominal cavity. Later extirpation of the transplant showed that the transplant had been the only organ secreting insulin in the animals. The transplanted dogs had normal basal plasma glucose and IRI concentrations, a reduced IRI reaction and glucose tolerance after i.v. glucose application. The early reflex increase in IRI concentration after oral glucose intake or meal feeding was observed in all control animals but not, in contrast, in the transplanted animals. The authors conclude that the early insulin secretion phase is entirely due to nerval influences.

Animals↗
PubMed1982

Comparison of peripheral and portal venous insulin administration on postprandial metabolic responses in alloxan-diabetic dogs. Effects of identical preprogrammed complex insulin infusion waveforms.

The optimal route for insulin administration by insulin infusion devices has not been established. To assess the differences between the peripheral venous and portal venous routes of insulin administration on postprandial metabolic responses, six alloxan-diabetic dogs were studied on four occasions. On the first, the insulin infusion rates given by the Biostator for disposal of a mixed meal were recorded electronically. On two subsequent occasions, these insulin infusion profiles were administered by a peripheral vein. On an additional occasion, the identical insulin infusion profile was given via the portal vein. No differences were observed in basal or peak plasma glucose, insulin, glucagon, branched chain amino acids, and lactate concentrations between portal and peripheral venous insulin administration. Furthermore, no differences in isotopically ( [2-3H]glucose) determined rates of systemic glucose appearance and disappearance were observed between the two routes. Although preprandial plasma alanine concentrations were greater when insulin was infused via the portal vein, the postprandial increments did not differ from those observed during infusion of insulin by a peripheral vein. These studies suggest that under the current experimental conditions, there appears to be no difference in the disposition of a mixed meal, measured as net whole body glucose appearance and disappearance rates, when insulin is administered in an open-loop fashion via either a peripheral or the portal vein.

Alanine↗
PubMed1982

Low dose streptozotocin diabetes after partial pancreatectomy in dogs. Histological findings in a new type of experimental diabetes.

Permanent diabetes was produced in 16 out of 55 dogs by partial pancreatectomy (77% of the calculated organ weight) and simultaneous infusion of 2 mg/kg streptozotocin into the superior pancreaticoduodenal artery. The animals exhibited hyperglycemia, absolute lack of endogenous B-cell function, and ketosis, but no exocrine pancreatic insufficiency. 21 animals needed up to 7 additional subsequent intravenous streptozotocin injections (15 mg/kg each at intervals of 3 days). In 18 animals the procedure failed to render them diabetic; they died mainly from toxic effects of the drug. There were severe pathohistological changes in all streptozotocin-treated animals. Besides the well known alterations of the islets of Langerhans, lymphocytic inflammations were found in numerous organs including the exocrine pancreas. In most cases they were combined with degenerative changes of the organ parenchyma, particularly in kidney and liver. These findings were not correlated to the sex of the animals, to the occurrence and severity if diabetes, to the time of survival, or to the streptozotocin dose applied. But they were obviously related to the clinical picture existing besides diabetes. It is concluded that the model of experimental diabetes presented might be useful in a carnivorous big animal species but that toxic streptozotocin effects are to be expected when the dose administered exceeds 2 mg/kg.

Animals↗
PubMed1982

[Topochemical and electron microscopical analysis of the pancreas of dogs after pancreatic denervation].

Histochemical and electronmicroscopic findings on chronically and selectively denervated pancreata of 8 dogs are described. Most nerve fibers showed marked degeneration and perineuritis, and there was an inflammation of intrapancreatic ganglia. There was no change in the number of islets or in the A-B-cell ratio. Insulitis frequently has been observed. Both immunohistochemically demonstrable insulin in the B-cells, and glucagon in the A-cells were reduced in relation to that in non-denervated controls. There were single A- and B-cells within the acini in an apparently normal frequency. Many pancreata showed a chronic infiltration and fibroblastic inflammation within the acini but their extent varied considerably between the animals. Intrapancreatic blood vessels were generally dilated, hyperemic, and perivascular fibrosis was seen in some cases; the vessels contained many leucocytes. Acinar cells were often subjected to vacuolic degeneration. Another part of them showed, however, increased appearance of ergastoplasm, mitochondria, and of Golgi apparatus as a sign of increased functional stimulation. There were fibrosis and mononuclear infiltration in the medium-sized and large pancreatic ducts.

Animals↗
PubMed1982

The influence of selective pancreatic denervation on plasma insulin and glucose tolerance in dogs.

The mechanism of reflex plasma insulin responses after oral stimulation and the influence of autonomic control on glucose- and meal -induced insulin secretion needs to be elucidated. Dogs with chronic pancreatic fistulas were studied two months after selective pancreatic denervation or bilateral truncal vagotomy and compared with fistulated controls. The normal glucose- and amino acid-independent insulinogenic reflex after an oral glucose load or after a meal was inhibited in the experimental groups. Glucose-related insulin secretion (oral or intravenous loads) and glucose tolerance were clearly reduced after vagotomy, but only partly diminished in the denervated animals. The plasma insulin increase after meat ingestion was inhibited in both experimental groups. It is concluded that the B-cells work under integrated tonic control of both the vagal and the sympathetic systems. Independent of this control, a vago-vagal insulinogenic reflex is initiated by enteric stimuli. These two mechanisms might be considered as part of the gastroentero-pancreatic axis in a broader sense.

Animals↗
PubMed1981

[The use of artificial beta-cells or programmed insulin infusions in the therapy of insulin-dependent diabetes mellitus].

Completing the article 36, 19-26 (1981) of this journal, the indications for feedback-controlled ("closed-loop", artificial B-cell) and for glucose-independent ("open loop") insulin infusions are defined exactly. So far the artificial B-cell can be used as a bedside equipment only. Its application is restricted to a small number of diabetics who are difficult to be treated. In these cases, some improvement of insulin injection therapy can be obtained by means of so-called normoglycaemie intervening days and by the assessment of the "real" need of insulin using an artificial B-cell. Under certain conditions, open-loop insulin infusions seem to be advantageous both as continuous nocturnal basal rate administrations or as automated whole day infusions with the basal rates supplemented by extra doses to cover the meals. This should, however, be confirmed by controlled studies under ambulatory conditions.

Diabetes Mellitus↗
PubMed1981

[Use of an artificial B-cell in clinic and experimental medicine].

Long-term hyperglycaemia in diabetics favours the development of diabetic microangiopathy. The clinical research, therefore, aims to find new opportunities to obtain normoglycaemia in insulin-dependent diabetics mainly by following three patts: -transplantation of pancreatic tissue or isolated islets of Langerhans - implantation of so-called hybrid pancreas and -construction of an artificial B-cell. This paper gives a review of the development, principle of function and clinical application of the glucose controlled insulin infusion system (closed loop system) and of the so-called open loop system without feedback to the glucose values. Results of our own investigations with GCIIS "Biostator", the development of an algorithm of our for the correlation between glucose and insulin behaviour and the first results with the insulin therapy with micropumps (open loop system) were demonstrated and discussed critically.

Blood Glucose↗
PubMed1981

A physiological solvent for crystalline insulin.

Insulin is insoluble in water at physiological pH, but dissolves relatively rapidly in plasma. To quantify the ability of various solutions to dissolve crystalline insulin, a simple assay measuring dissolution time was developed. At pH 7.5 and room temperature, distilled water, 0.154 mol/l NaCl, Ringer's lactate solution, and 5% albumin in 0.154 mol/l NaCl did not dissolve insulin crystals within 30 min. Normal postprandial human plasma and a protein-free cell culture medium dissolved insulin crystals within 3 to 8 min. This ability was inhibited by acid titration of the fluids to a stable pH of 6.30, at which point bicarbonate depletion could be implied. Repletion of bicarbonate did restore the ability of these solutions to dissolve insulin crystals, but back-titration to the initial pH with NaOH did not. The effect of sodium bicarbonate alone was strongly concentration dependent above 23 mmol/l. We suggest that the ability of physiological fluids to dissolve insulin crystals at normal pH depends on their bicarbonate content. The ability to dissolve insulin with a physiological solvent which prevents its reaggregation promises to facilitate its use in portable pumping systems.

Adult↗