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Biomedical subjects

G Albrecht

Publications and source records attributed to G Albrecht.

At least 91 records · Page 5Linked to original sources

Serum magnesium in insulin-dependent diabetics and healthy subjects in relation to insulin secretion and glycemia during glucose-glucagon test.

UNLABELLED: In order to investigate the influence of insulin secretion on serum magnesium concentrations 33 insulin-dependent diabetics and 10 control subjects were studied. The residual insulin secretion (RIS) was investigated by measurement of human C-peptide (HCP) before and after stimulation during on OGTT (1.75 mg/kg)-glucagon (i.v. 0.1 mg glucagon/kg)-test. RESULTS: Certain RIS existed in 11 insulin-dependent diabetics, 12 were without any RIS (uncertain RIS in 10 patients). Glucose tolerance and daily glycemia differed significantly among the two groups. However, all diabetics were far from euglycemia, (3.3-9.3 mmol/l): Fasting plasma glucose 12.0 +/- 0.9 (certain RIS), 15.0 +/- 0.8 (no RIS), 13.9 +/- 1.8 (uncertain RIS). Serum magnesium was significantly lower in all diabetics, both before and during the test. There was no change during the OGTT-glucagon-test and no difference among the three groups of insulin-dependent diabetics. So, we conclude that a small RIS in our longterm insulin-dependent diabetics has no influence on the behaviour of serum magnesium. But, magnesium depletion can influence coronary blood flow, blood clotting, and atherogenesis. Therefore, it should be necessary to pay more attention to the hypomagnesemia in insulin-dependent diabetics.

Adult↗

In vivo comparison of different algorithms for the artificial beta-cell.

Using an extracorporeal artificial beta-cell in chronically diabetic dogs, the effects of four different mathematical models of glucose-controlled insulin dosage were compared: the Biostator algorithm (quadratic equation), Toronto algorithm (hyperbolic tangent function), Karlsburg algorithm (modified first-order derivative controller), and Ilmenau algorithm (second-order linear difference equation). The constants of all formulas implemented for the artificial beta-cell were obtained by regression analysis of paired blood glucose and plasma insulin data from normal control animals. Thus, they were biologically equivalent for all formulas. The patterns of blood glucose, insulin doses, and plasma insulin before, during, and after an intravenous glucose infusion test performed during the glucose-controlled insulin infusion showed no significant differences between the experimental groups subjected to the different algorithms. However, in no case were really normal blood glucose response curves restored by the artificial beta-cell. This might be due, first, to the fact that the algorithm parameters were not adapted to the actual individual insulin responsiveness, second, to the unphysiological peripheral venous route of insulin administration, and, third, to the lack of appropriate adaptation of the animals to normoglycemia.

Animals↗

[Undesirable skin reactions to lithium].

Lithium plays an important role in the treatment and prophylaxis of affective psychoses. Taking lithium-containing drugs by mouth can cause side effects on the skin, although severe side effects are rare. Acneiform dermatoses have been most frequently described. In addition, when taking lithium continuously, psoriasis can be triggered or worsened and the psoriasis tends to be resistant to treatment. Maculo papular eruptions, ulcers, keratosis pilaris like folliculitis, exfoliative dermatitis, dermatitis herpetiformis like eruption, and hair loss have been described. Possibly the blood level of lithium plays a decisive role in developing a dermatosis. If the skin side effect is mild, the dermatosis should be treated topically. If the dermatoses under lithium treatment are severe, a reduction in the lithium dosage should possibly be discussed with the psychiatrist. Only rarely does lithium have to be entirely discontinued.

Acne Vulgaris↗

[Serous borderline ovarian tumors].

Proliferating papillary serous cystadenomas that seldom occur are classified into the group of ovarian tumours of low malignant potential (borderline tumours). The present study includes 33 cases observed in our clinic since 1955. Even though the five-year survival rate being 88% was substantially higher than that for ovarian carcinomas, the prognosis of individual cases cannot be reliably predicted because of the uncertainty as to the biological behaviour in both clinical and histological terms. Consequently, the trend to predominantly radical surgery appears to be a justified approach. Whenever it is desirable to maintain fertility in younger women, conservative surgery would require a unilateral tumour without a ruptured capsule and normal histological findings to be obtained from wedge excision in the opposite ovary.

Adult↗

[Tumor degeneration of an autogenous ovarian transplant].

At a woman, at that time only 27 years old, because of a one-sided ovarian tumour, the abdominal hysterectomy with the resection of both appendages had been carried out. At the same time the other ovary macroscopically without pathological findings had been implanted into the Retzius cavity, where later it degenerated tumourously like the histological picture of a cystoma serosum papilliferum proliferans. Since the resection of the second tumour, which was carried out 28 years after the first operation, there has been found no more manifestation of a tumour up to now.

Adult↗

Configuration of beta-globin messenger RNA in rabbit reticulocytes. Identification of sites exposed to endogenous and exogenous nucleases.

Masked and exposed sites in rabbit beta-globin messenger RNA were identified through S1 nuclease mapping of RNase T1 cleavage sites. Sites exposed to this enzyme were compared in deproteinized polysomal RNA and in mRNA in its native configuration in reticulocyte extracts. The analysis showed that most of the 3' non-coding region is well accessible to the enzyme, both in deproteinized RNA and in the cell extract. A possible protecting function for the poly(A) sequence is suggested by the fact that molecules with very short poly(A) segments were cleaved preferentially in this region. The G residues in the 5' non-coding region were inaccessible to RNase T1. A highly sensitive site adjacent to the initiation AUG codon was evident in the deproteinized RNA. This site was far less accessible to the enzyme in the mRNA associated with ribosomes in the cell extract. The first 150 nucleotides in the coding region showed very little susceptibility to digestion by the enzyme, in deproteinized RNA as well as in the cell extracts. Preparations of untreated mRNA showed the occurrence of truncated molecules, apparently generated by cleavage by endogenous nucleases. These cleavages were most prevalent in the two non-coding regions. They occurred at sites containing A-U sequences in the 3' non-coding region, and at sites with different sequences in the 5' non-coding region. Incubation of cell extracts at 37 degrees C did not cause any increase in these endogenous cleavages. It is suggested that they may have been generated in the intact cells, possibly as part of the mRNA degradation process in maturing reticulocytes.

Animals↗

Results of treatment with continuous subcutaneous insulin infusion (CSII) in insulin-dependent (type I) diabetics.

10 labile insulin-dependent diabetic patients treated with CSII were followed up for 6 to 16 months under conditions of everyday life. The mean blood glucose (MBG), glycosylated haemoglobin (HbA1), motor nerve conduction velocity (MCV), and respiratory heart arrhythmia at rest (RHA) were investigated. A significant improvement of metabolic control was observed (MBG 8.03 +/- 1.40 vs 5.18 +/- 0.87 mmol/l, p less than 0.01; HbA1 10.7 +/- 1.3 vs 8.7 +/- 1.6%, p less than 0.05) in comparison with the control values under intensified conventional therapy. MCV increased gradually but the average RHA remained unchanged. The psychological examination employing a questionnaire reflects that all patients selected were highly motivated and that their positive attitudes were further stabilized during pump treatment. An average of three mild hypoglycaemic episodes occurred per month per patient; these were no more than under intensified conventional treatment. Other minor clinical and technical complications occurred at a total frequency of one per month per patient and did not achieve therapeutical relevance.

Adult↗

Long-term improvement in metabolic control of unstable type I diabetes by s.c. insulin injection patterns based on the dose profiles required by bed-side artificial beta-cell.

Twenty unselected unstable type I diabetic inpatients whose blood glucose control was insufficient employing three daily s.c. injections of regular insulin supplemented by intermediate acting insulin were subjected to a 48-hour treatment with the Biostator -GCIIS when both diet and muscular exercise were kept as close as possible to the conditions at home. The s.c. injection regimen was adjusted to the insulin dose pattern required by the artificial beta cell. There was significant metabolic improvement in 16 out of the 20 patients on discharge, in comparison to the pre-Biostator conditions. This improvement was still present when the patients were re-admitted after an average of seven months. It is concluded that in certain cases of unstable type I diabetes mellitus the metabolic re-arrangement based on intercalary days on an extracorporal artificial beta cell might be useful if the control constants are adapted to minimize the insulin requirement by the machine.

Adolescent↗

Methods and effects of improved conventional insulin treatment in labile insulin-dependent diabetes (IDDM).

In 92 particularly unstable IDDM patients we have tried to avoid any gap in daily insulin supply by applying one out of four newly designed combinations of regular and depot insulin. The short-term effect after three weeks and the long-term effect after greater than or equal to 12 months (data from 30 patients only) of these new regimens were compared with those of the traditional regimen in a retrospective evaluation: Glycemia (level and excursions) was significantly improved both after three weeks of inpatient treatment and after greater than or equal to 12 additional months on outpatient regimen. Serum beta-LP and HbA1 showed slight decrease during long-term follow-up. The majority of the patients reported improved well-being under conditions of daily life. However, the glycemia achieved was still far from the permanent euglycemia aimed at. For the avoidance of any gap in insulin supply in labile diabetics four insulin injections are necessary in most cases. For this, individually tailored combinations of regular and depot insulin must be drawn up carefully together with the patients to avoid a " strait -jacket" system which would not work under conditions of daily life.

Adult↗

Estimation of individually adapted control parameters for an artificial beta cell.

For optimum long-term glycemic regulation using a miniaturized artificial beta cell it is indispensible to estimate control parameters suited to the individual requirements of each diabetic patient. To solve this problem, a strategy has been developed which is based on engineering optimum-control theory with a model involving glucose and insulin interactions. The model considers physiologically relevant unit processes like endogenous glucose production, insulin-independent glucose uptake from its apparent distribution space, insulin-dependent glucose utilization, glucose-dependent insulin supply, and insulin catabolism. The assumed model structure is validated by results obtained in experimentally diabetic dogs using partition analysis. The individual parameter values of the model are obtained by a digital computer procedure based on a simple test which involves a bolus injection of glucose + insulin when a constant basal insulin dose is being administered in the diabetic in whom normoglycemia was re-established before the test. The method presented is recommended for future use in all cases where an optimized insulin regimen is to be worked out.

Animals↗

Modelling the glucose-insulin system as a basis for the artificial beta cell.

The control constants for glucose-dependent insulin dosage in diabetic dogs were determined from test results in the opened system on the basis of a global blood glucose plasma-insulin control model. The controlled plant of the model consisted of the glucose and insulin subsystems; the entire insulin providing process was considered to be the controlling element, and the glucose-dependent insulin dose estimation, the controller. The constants obtained were employed in the extracorporeal artificial beta cell. The structure of the model and the numerical values of its state variables were verified by the prediction of blood glucose responses to intravenous glucose loads and by the correspondence between glucose balances and insulin doses as calculates and those as observed in diabetic animals. The application of the optimum control constant estimates in feedback-controlled insulin infusions provides improved blood glucose patterns but unchanged needs for insulin in comparison to the application of standard control parameters.

Animals↗

Tracer kinetic studies of glucose and alanine metabolism in diabetic dogs on the artificial beta cell.

The in vivo glucose turnover was investigated employing [6-3H]glucose and [U-14C] glucose or [6-3H]glucose and [U-14C]alanine. Fasting chronically diabetic dogs at rest during short-term treatment with a bedside artificial beta cell were compared with normal animals in a glycemic steady state before, during, and after an i.v. load of unlabelled glucose. The insulin was infused into a peripheral vein. During the glucose-controlled insulin infusion glycemia was perfectly normalized, the concentrations of lactate and alanine remained elevated, pancreatic glucagon returned to normal, and the peripheral insulin levels were normal or slightly elevated in the diabetic dogs. Also the glucose turnover was in the normal range but the recirculation of the carbon label (i.e. the Cori cycle activity) was reduced. The alanine turnover and gluconeogenesis from alanine remained increased both in the basal state and during the glucose load. It is concluded that due to the absence of the physiological portosystemic insulin gradient, complete restoration of the physiological metabolic rates and control relations is not possible even if the blood glucose patterns are fully normalized.

Alanine↗

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↗

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↗

Diurnal rhythm of insulin sensitivity in subjects with normal and impaired glucose tolerance.

We studied the insulin sensitivity in 5 normal subjects and 5 subjects with impaired carbohydrate tolerance using the glucose controlled insulin infusion system (BIOSTATOR). During a fixed glucose infusion rate of 2 mg/kg b.w./min, the computer program was set to maintain the plasma glucose concentration at 4.44 mmol/l. The ratio of infused exogenous insulin to infused glucose served as a measure of insulin sensitivity. Calculating the average insulin glucose ratio for 24 hours, the mean values amounted to 3531 and 9319 ng/gm (p less than 0.01) in subjects with normal and impaired carbohydrate tolerance, respectively, indicating that insulin resistance is the main cause of decreased glucose utilization in the latter group. Circadian rhythms of insulin sensitivity occur in both groups in a similar fashion. The insulin sensitivity was higher in the afternoon (1200-1800) as compared to the night. Thus, diurnal variations in insulin sensitivity are independent of disturbances of glucose metabolism.

Blood Glucose↗