[Diet from a preventive and therapeutic view point--diabetes mellitus].
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to W Bruns.
Explore the source record for details and available documents.
The present study focussed on the impact of heavy muscular work upon metabolic homeostasis in insulin dependent (type I) diabetics in situations involving a certain degree of hyper- and hypoinsulinemia. 20 juvenile type I-diabetics were compared with 6 nondiabetic healthy subjects. The diabetics were studied in states of hypo-(trial A) and hyperinsulinemia (trial B) at the start of the exercise. Differences in insulin availability resulted from the different times that had elapsed from the last insulin injection (3 hours in trial A and 1 hour in trial B) before the ergometer test started at 7 a.m. Six diabetics out of 20 patients were studied in both trials A and B to establish the reproducibility of metabolic reactions to the exercise. Bicycle ergometer tests were carried out in the upright position at 5 graded steps of 50 W, 75 W, 100 W, 125 W and a load near to exhaustion. Rest periods of five minutes were allowed between these work periods for taking blood samples before and after each work load. Plasma glucose, FFA, glycerol, lactate, alanine, IRI and HCP concentrations were investigated. The blood pressure at rest and during exercise was measured, and the physical working capacity (PWC170) was calculated according to Wahlund on the basis of the heart rate response to exercise. The results of the exercise tests reflect clearly the different metabolic reactions to heavy muscular work despite the relatively slight differences in insulin availability at the start: --Exhausting muscular work during the hypoinsulinemic state resulted in hyperglycemia and exaggerated lipolysis. --Heavy muscular work in a hyperinsulinemic state resulted in a reduced blood glucose level and antilipolytic reactions in comparison to nondiabetics. These findings suggest the great necessity of an adequate insulin availability during heavy muscular work in juvenile type I-diabetics.
The long term effect of clofibrate treatment on the carbohydrate and lipid metabolisms and on insulin secretion was studied in subjects with primary hyperlipoproteinemia and impaired glucose tolerance. Treatment consisted of a diet and 2.0 g clofibrate per day. The body weight, triglyceride and cholesterol levels, glucose tolerance and insulin secretion of 14 patients were monitored for five years. During the first year of treatment the mean triglyceride and cholesterol levels decreased by 80% and 40% respectively. The cholesterol level became fully normal in the course of further treatment, but the triglyceride level did not. The mean reduction of body weight over the five-year period amounted to 5.0 kg. Improvement in glucose tolerance was shown by a significant increase in Conard's glucose assimilation coefficient. Glucose tolerance became completely normal in some cases. In one case diabetes mellitus became manifest. Improvement of the glucose tolerance was accompanied by reduction of glucose-stimulated insulin secretion by about 50% of the original value. The results permit the conclusion that the use of clofibrate for the long-term treatment of hyperlipoproteinemia is still justified. If hyperlipoproteinemia is accompanied by impaired glucose tolerance, clofibrate can also be regarded as having a certain antidiabetic effect during the normalisation of the "metabolic syndrome".
The development of portable insulin infusion devices - in which the insulin dosage is programmed in advance (open loop system) are increasingly being used for long-term daily diabetes control. These pumps represent a new method for attaining significantly improved metabolic control (glycemia and glucose metabolites, HbA1, lipid and aminoacid metabolism) and an impressive influence on diabetic neuropathy, on general fitness and on quality of life of insulin-dependent diabetics. At least all insulin-dependent diabetics without noticeable residual insulin secretion should be treated by continuous subcutaneous insulin infusion (CSII) via portable pumps, that are 8 000-10 000 patients in the GDR and approximately 500 000 in the world. Considering special conditions (strict supervision by experienced medical staff, carefully drawn up adequate instructions, highly motivated and capable patients) we assume that at the present stage of technical development of the pumps infants, imbeciles and incooperatives should be excepted only.
Transfer of a 36-kilobase piece of human DNA containing the beta-interferon (IFN-beta) gene into mouse Ltk-cells leads to transient expression of human interferon even without an exogenous inducer. A low level of human interferon expression is also found in most stable clones containing the transferred DNA. With double-stranded RNA or Newcastle disease virus (NDV) as inducer, human interferon expression is greatly increased. The induced transcript is identical to normal human IFN-beta mRNA. Neighbouring genes contained on the transferred DNA are co-induced but are not essential for the production of human interferon in mouse L cells.
Explore the source record for details and available documents.
A report is given on experience gained during the electroneurographic examination of 800 diabetics of all ages and on the results of respiratory heart arrhythmia measurement on 215 diabetics. It is proposed that diabetic nervous disturbances should be divided into the following groups: 1--early diabetic and subclinical disturbances, 2--somatovisceral polyneuropathy in type I diabetics, 3--polyneuropathy in type II diabetics, 4--mononeuropathy, mononeuropathy multiplex and proximal amyotrophy. The disturbances in group 1 can be reversed by metabolic control. Only the PNP in group 2 shows a firm statistical correlation to duration of diabetes mellitus and to microangiopathy. This appears to be a dying back neuropathy, probably caused by the chronically catabolic metabolic situation.
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.
The isolation of a human genomic cosmid hybrid containing the interferon beta gene has recently been reported (Gross et al., 1981). This hybrid was mapped using single and double digests and cross-hybridisation with the sub-cloned EcoRI and BgIII fragments. Purified fragments and subclones were used as hybridisation probes against chromosomal "Southern" blots to show that at least half of the region has been cloned without alteration. This cannot at present be confirmed for the rest of the region due to the presence of highly repetitive DNA on these cloned fragments. Sequencing data on the 5'-end of the fibroblast IFN-beta gene shows a high density of direct and inverted repeats. The IFN-beta mRNA coding region contains no intron, although the possibility of other transcription starts is not ruled out. The cloned region shows no similarities to known genomic clones containing IFN-alpha genes.
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.
On the basis of the estimation of the plasma glucose and the insulin concentrations in 10-minute intervals during 24 hours by the mathematical analysis (multiple regression) over relations between the behaviour of plasma glucose and insulin concentration insulin secretion rates independent of plasma glucose can be calculated. In non-diabetics a circadian rhythm of the disposal of insulin - independent of food - is established. Thus the secretion rate increases in the early morning hours still before before the first meal and is maintained in different size up to nearly 18 o'clock. Then it established itself to the level of the nocturnal basal rate. Adequate changes of the insulin need during night are proved in diabetics without endogenic residual insulin secretion by means of the artificial B-cell Biostator. The circadian rhythm of the disposal of insulin take place parallel with adequate changes of other biological parameters and is of importance for the practice of the conventional insulin therapy as well as in the future use of non-measuring value-regulated insulin infusions (open-loop system).
Binding studies with penicillins other than penicillin G are rare in staphylococci. Therefore the binding of a series of penicillins to the isolated cytoplasmic membrane of S. aureus H was examined indirectly by inhibition of (14C)-penicillin G binding. Biphasic inhibition curves were obtained with the beta-lactamase-insensitive penicillins as well as with ampicillin, ciclacillin, and 6-aminopenicillanic acid (6-APA) indicating that there are at least two types of targets. 60--75% of them were those with a high affinity of 10(7)--10(8) l/mol, the affinities of the second type of binding sites being in the range of 10(4)--10(5) l/mol (except 6-APA: 10(5) l/mol resp.). Monophasic binding curves were produced by penicillin G, penicillin V, propicillin, mezlocillin, azlocillin, carbenicillin, ticarcillin and mecillinam. With both groups of penicillins reversible binding to some extent was found. From comparative analysis of the binding of particular penicillins it can be finally concluded that there exist four types of binding sites in staphylococcal membranes. This agrees with the current state of knowledge in the field of penicillin-binding proteins. A good correlation was found between the 50% binding value and the minimum inhibitory concentration for most of the penicillins. As half saturation also with the "biphasic" penicillins was always achieved by (irreversible) binding to the high-affinity targets, it may be suggested that the low-affinity binding sites are probably not related to the antibacterial action of penicillins in staphylococci.
It is reported on one for practice rational method for the determination of HbA1c. Methodical problems of its realization are pointed out. By the selection of suitable buffers short separating times can be achieved without any high expense of apparatuses. We have simplified the manufacture of haemolysates from venous blood to be separated chromatographically by the use of capillary blood. We did not find any significant differences between the values from venous and capillary blood. The valency of HbA1c for the purpose of estimation of the metabolic situation in diabetics during a longer period is explained with the help of literature, and the normal values in healthy test persons are represented.
Insulin secretion rates after glucose loading were calculated from peripheral venous IRI concentrations considering half life and distribution space of exogenous insulin in normal men and dogs. The coefficients of multiple linear regression analysis between insulin secretion rates and plasma glucose (level and order and rate of change) were used as algorithm parameters in glucose-controlled insulin infusions. These were carried out in each dog based on individual estimations before the induction of diabetes but in the diabetic patients based on values derived from a group of normal subjects. Using this formula, nearly normal patterns of glucose and of insulin were observed in diabetic men and dogs under basal conditions and after IV glucose loading but not after meals. This algorithm enables selection of the parameters prospectively. The effect of a parameter combination depends on insulin sensitivity and it should be appropriately adapted. In the diabetic patients there was no predictable influence of the brittle or stable characteristics of the disease nor of insulin antibodies on the glucose curves obtained with glucose controlled insulin infusions.
In staphylococci (and other gram-positive bacteria) the phenotypical expression of intrinsic penicillin resistance as well as the frequency of this resistance are unknown. A permeability barrier in the cell wall, as it was established in gram-negative bacteria, is unlikely in staphylococci and was excluded by experiments with whole cells. Assuming that in staphylococci intrinsic resistance is also located in the cell envelope, the cytoplasmic membrane should be the site of responsibility. Therefore the binding of (14C)-penicillin G to the isolated membrane fraction of four staphylococcal strains resistant to penicillin G was studied. Two strains showed an additional resistance to methicillin, one of them was penicillinase-negative. Compared with two sensitive strains the penicillin binding was greatly reduced in the membranes of the resistant ones. This was not due to a loss of specific receptors. The maximum specific binding capacity of about 20 nmol of (14C)-penicillin G/g membrane protein was found in the resistant strains as well as in the sensitive controls. Furthermore penicillin G irreversibly bound also in the resistant bacteria. Differences, however, were found regarding the affinity of the binding sites for penicillin. In all resistant strains it was reduced by a factor of about 500. Our findings confirm the assumption that in staphylococci the mechanism of intrinsic penicillin resistance is located in the cytoplasmic membrane. They can best be explained when considering that not the penicillin binding components themselves but the membrane structure in their environment is altered thus preventing the access of the antibiotic to its site of action in the membrane. In addition, the homogeneity of our results indicates that intrinsic resistance to penicillin G is, contrary to current opinion, a general phenomenon in resistant staphylococci.
Explore the source record for details and available documents.
Sensory conduction velocity of the median nerve, motor conduction velocity of both median and tibial nerves, and corresponding distal laterncies are sufficient parameters to establish the diagnosis of polyneuropathy almost with certainty. Considering these six parameters yielded in detection of peripheral nerve dysfunction in 22% of diabetic patients who were free from clinical signs of polyneuropathy. Electroneurographical findings in 340 out of 677 patients with diabetes mellitus were interpreted as evidence of segmental demyelination. Within this group there was the majority of patients with clinical signs of polyneuropathy and with subclinical signs of peripheral nerve dysfunction. There existed a positive correlation between signs of nerve dysfunction with angiopathy, age and duration of the disease. A second group consisting of 243 diabetics with signs of incipient segmental demyelination with or without signs of axonaal degeneration mainly included juvenile patients with a short duration of the disease and with a low frequency of angiopathy.
789 patients with diabetes mellitus were studied by clinical and electroneurographical investigation. Motor and sensory conduction velocities of the median nerve and motor conduction velocity of the tibial nerve were determined. 86.1% of the patients suffered from juvenile diabetes, and 13.9% from maturity onset diabetes. Average duration of the disease was 9.5 years, average age of the patients was 26.7 years. Clinical signs of polyneuropathy were found in 19.1%. In 40.9% of the patients at least one of 3 conduction velocities was found to be delayed. Patients with clinical signs of polyneuropathy exhibited delayed nerve conduction velocities and delayed distal latencies. Diagnosis of polyneuropathy almost with certainty is possible by determining the three nerve conduction velocities and the three corresponding distal latencies. 22% of patients without clinical signs of polyneuropathy exhibited electroneurographical signs of impaired peripheral nerve function. Heredity, body weight, lipid metabolism, actual metabolic balance, and treatment were found to be without any significant influence on nerve conduction velocity.