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Biomedical subjects

B Schulz

Publications and source records attributed to B Schulz.

At least 109 records · Page 6Linked to original sources

Clinical course in insulin-dependent diabetics undergoing hemodialysis.

Nephropathy continues to be the most serious complication in type I-diabetics. When we started chronic hemodialysis in these patients 15 years ago survival figures were poor. Later on the survival rate for diabetics undergoing hemodialysis has improved progressively. The aim of this report was to present our own experience in hemodialysis treatment of insulin-dependent diabetics. The cumulative survival rate of 46 insulin-dependent diabetics undergoing hemodialysis has increased progressively and now amounts to 70% after one year, and 50% after two years of treatment. At the same time we could attain a certain improvement of metabolic control. Nutrition has also been improved, as indicated by increased transferrin (p less than 0.05) and stable serum protein levels. Systolic blood pressure control became better (p less than 0.05) but, a fluid overload was still present. Here, further improvements are necessary to increase the survival rate. Therefore, the survival of diabetic patients with hemodialysis may be approaching that of non-diabetics. In some patients retinopathy was improved after one year of treatment. Despite a better prognosis for survival in diabetics treated by chronic hemodialysis we suggest that the successful renal transplantation should be the treatment of choice in patients suffering from diabetic nephropathy. In general, hemodialysis and renal transplantation should be started earlier than hitherto, i.e. already at creatinine levels of about 600 mumol/l, and at urea levels of 30 mmol/l. Strict metabolic and blood pressure control, as well as early laser coagulation therapy of retinopathy should be instituted for patients with creatine levels above 200 mumol/l, in close cooperation of a diabetologist, nephrologist, and ophthalmologist. This will be our future therapeutic strategy for these patients.

Adult↗

Metabolic, hormonal, and immunological alterations in subjects with antecedent mumps infection.

Since mumps virus seems to be one of the most likely candidates in viral etiology of insulin-dependent diabetes (IDDM) we studied the possible relationship of glucose tolerance (75 g oGTT), beta cell function, diabetes associated HLA antigens, haptoglobin phenotype, islet cell antibodies (ICA) and islet cell surface antibodies (ICSA) in 125 subjects with antecedent mumps infection. Impaired glucose tolerance (IGT) was diagnosed in 3.2% (n = 4) but onset of diabetes did not appear within 14 months after mumps infection. There was no relationship between glucose tolerance and complications of antecedent mumps infection (e.g. pancreatitis, meningitis, orchitis). The prevalence rate of ICA was 76%. ICSA were detectable in about 36% of children and 62% of the adults tested (p less than 0.01). There was no relationship between ICA/ICSA and diabetes-associated HLA antigens, haptoglobin phenotype or beta cell function (fasting C-peptide and insulin response to 75 g oGTT). However, adults with circulating ICA were characterized by a significantly lower insulin response to glucose. Fifty two "risk" subjects characterized by IGT, diabetes associated HLA antigen(s), ICA or ICSA either alone or combined were studied again 26 months after mumps infection. No symptomatic diabetes appeared and IGT was diagnosed in one case only. ICA and ICSA persisted in more than 50% of subjects in whom ICA or ICSA were present 14 months after mumps infection. Since the used immunological techniques do not clearly distinguish organ-specific from non-organ-specific antibodies the results must be interpreted with caution. To summarize, the preliminary results do not support a close temporal relationship between mumps infection and the onset of IDDM. The pathogenetic role of mumps virus and ICA/ICSA and their possible relation to a slow progressive beta cell destruction has still to be determined.

Adult↗

[Structure-release relationships of active polymeric drug combinations. 1. The influence of polymer structure on the diffusion of 3-methylpyrazole from monolithic systems].

The release of 3-methylpyrazole from monolithic polymer films into aqueous media has been studied. The diffusion of the active agent decreased with increasing of the content of acetate groups in reacetylated poly(vinyl alcohols) and with increasing of the ester lengths in copolymers of maleic esters, respectively. The release rate of active ingredient is dependent on the hydrophilicity of the polymer films. Contrary to the glass transition temperature the hydrophilicity of polymers expressed the interaction between polymer chains and water in a direct way. The hydrophilicity of copolymers of maleic esters correlated with the turbidimetric point, which can be determined by acidimetric titrations. The influences of interactions between polymers and the active agents on their diffusion in the polymers were also discussed.

Chemical Phenomena↗

Tolbutamide does not alter insulin requirement in Type 1 (insulin-dependent) diabetes.

We examined whether tolbutamide has any acute or short-term effects on insulin action in Type 1 (insulin-dependent) diabetes. A euglycaemic glucose clamp was performed in seven Type 1 diabetic patients without clinical insulin resistance by infusing glucose at a constant rate of 0.01 mmol X kg-1 X min-1 for 3h together with a simultaneous insulin infusion using an 'artificial pancreas'. The insulin infusion rate required to maintain blood glucose at 6.7 mmol/l at a set low glucose infusion rate provides an index of insulin action in vivo. The euglycaemic clamp was performed on 3 separate days in the same patient: (1) in the basal state; (2) during simultaneous intravenous tolbutamide infusion of 0.5 g/h, and (3) after treatment with 2.5 g tolbutamide/day for 6 days in addition to insulin. The insulin infusion rate needed to maintain the set blood glucose level did not differ significantly between the three experimental conditions (1.2 +/- 0.2 versus 1.3 +/- 0.3 versus 1.2 +/- 0.3 U/h). Plasma glucagon, growth hormone, non-esterified fatty acid and glycerol levels did not differ between control or sulphonylurea treatment studies. The results suggest that tolbutamide does not exert any acute or short-term effects on insulin action in vivo in Type 1 diabetes. Our results do not provide support for the idea that this agent is a clinically useful adjunct to insulin in such patients.

Adult↗

Does insulin down-regulate its own receptor on erythrocytes in vitro?

The purpose of this study was to examine the in vitro effect of insulin on its own receptors on erythrocytes. Whole blood from 6 fasting normal and 6 diabetic (type II) subjects was incubated without or with exogenous insulin for 5 hours. The insulin binding to erythrocytes was then evaluated. At a tracer concentration, the percent 125I-insulin specifically bound amounted to 8.6 +/- 0.59% and 8.1 +/- 0.41% in fasting normal subjects and type II-diabetics, respectively. In contrast to in vivo studies, supraphysiologic insulin concentrations in the incubation medium did not alter significantly the insulin binding process. Thus, in vitro we could not demonstrate a down regulation of insulin receptor binding. It is likely that factors other than insulin are involved in the short-term regulation of insulin receptor affinity in man.

Erythrocytes↗

Islet cell antibodies in individuals at increased risk for IDDM.

Islet cell cytoplasmic antibodies (ICA), islet cell surface ( ICSA ) antibodies, HLA phenotypes, glucose tolerance, insulin secretion, and insulin sensitivity were studied in 16 twins of insulin-dependent diabetics as well as in 21 subjects with impaired glucose tolerance (IGT). 60% of the identical twins and 40% of the non-identical twins were ICSA -positive. The prevalence of ICSA in control persons was only 5%. ICA were found in all identical twins and in half of the non-identical twins. However, ICSA and ICA results were concordant in only 46% of the whole group of twins. There was no correlation between ICSA and either insulin secretion or insulin sensitivity. In the IGT subjects exhibiting low and normal insulin responses ICSA were observed in 67% and 23%, respectively. A high proportion of twins, but not of IGT subjects, had HLA DR3 or DR4 antigens which seem to confer genetic susceptibility to the development of IDDM. In the majority of DR3/DR4 twins, ICSA were also present. This might support the hypothesis of genetically-based autoimmunity, although the precise relationship between HLA and islet cell antibodies has to be clarified in a prospective study.

Adolescent↗

Heterogeneity of insulin response in relatives of type-I and type-II diabetics.

In 30 first-degree relatives (siblings or children) of type-I diabetics and 17 relatives (children) of type-II diabetics as well as in 19 healthy subjects a two-hour glucose infusion test (GIT, 12 mg/kg b.w./min) primed by a starting bolus of 0.33 g/kg b.w. was performed to evaluate carbohydrate tolerance (CHT) and insulin secretion pattern. After 4 to 5 years the test was repeated and the results were compared with those of the initial GIT. The glucose-stimulated insulin response of the early secretion phase (0--5 min) decreased during the follow-up study in relatives of type-II diabetics with normal CHT (in tendency) and with glucose intolerance (p less than 0.05) but not in relatives of type-I diabetics. A rightward shift of the glucose-insulin response curve was seen in the former group. Relatives of type-II diabetics with impaired CHT showed a striking abnormality in B-cell responsiveness. In relatives of type-I diabetics a disturbed glucose-insulin response curve could not be observed. The insulin response during the late phase of insulin secretion did not differ significantly among the groups. The conclusion drawn from our findings is that responsiveness of pancreatic B-cells seems to be directly affected genetically in first-degree relatives of type-II but not of type-I diabetics. Thus, diabetes mellitus cannot be regarded as one disorder with a similar genetic background.

Adult↗

Relationship between insulin secretion and pancreas morphology in subjects with chronic pancreatitis.

In order to investigate whether a relationship exists between in vivo insulin secretion and islet mass, 8 patients suffering from severe chronic relapsing pancreatitis were studied before and after pancreatectomy by glucose-glucagon-test (per os 1.75 g glucose; i.v. glucagon 0.01 mg/kg b.w.) and by intravenous glucose-tolerance-test (iGTT) (i.v. glucose 0.33 g/kg b.w.). Postoperative in vitro assessments of pancreatic insulin and alpha-amylase content were performed, and morphometric studies were carried out. Patients were characterized by reduced c-peptide secretion when compared with healthy subjects. The c-peptide response to the glucose-glucagon-test correlated well with the morphometrically estimated exocrine and islet tissue mass (P less than 0.05) and with the content of insulin and amylase in the tissue. The findings suggest that in subjects suffering from severe chronic relapsing pancreatitis the maximal insulin response might represent a parameter for the patient's islet mass.

Adult↗

[Multivariate analysis of the clinical care of underweight patients].

In a patient group of "underweight" persons, a total of 20 factors of the pregnant status, of the course of pregnancy and birth, as well as of the perinatal birth result, were tested by means of univariate analysis of variance and multivariate analysis of discriminance. Despite marked complexity of the influencing parameters and their interactions, it is shown that it will be approximately sufficient to pay attention to a few parameters to arrive at a comparable objectivation of overall clinical results. It is also evident that conclusions valid for direct obstetric and perinatal medical work cannot be arrived at from retrospective analysis alone.

Analysis of Variance↗

Metabolic and hormonal responses during a glucose controlled insulin infusion (Biostator) in subjects with impaired glucose tolerance.

The short-term effect of the glucose-controlled insulin infusion system (GCIIS) Biostator on metabolic and hormonal responses was studied in 10 non-obese subjects with glucose intolerance and insulin low response to glucose. Glucose tolerance characterized by means of a 2 h glucose infusion test (12 mg/kg/min) primed by i.v. injection of 0.33 g glucose/kg body weight was completely normalized by GCIIS. Results provide further support that normalization of glucose tolerance by means of GCIIS is accompanied by peripheral hyperinsulinaemia if compared with 33 non-obese healthy controls. Glucose-induced endogenous insulin secretion (C-peptide) was significantly reduced during the GCIIS study possibly due to inhibition of insulin secretion by exogenous insulin and/or by lower blood glucose concentration after normalization of glucose tolerance. Acute normalization of glucose tolerance in these patients failed to alter pancreatic glucagon, NEFA and glycerol responses but normalized paradoxical growth hormone response to glucose.

Adult↗

[Problems of monitoring metabolism of type I diabetics undergoing hemodialysis treatment].

The metabolic control of nephropathic type I diabetics dependent on dialysis is especially difficult and can be rendered more difficult by the procedure of haemodialysis, mainly due to the use of glucose-free dialysis fluid. The blood glucose level is reduced, resulting in hypoglycaemia. The purpose of this study was to compare the effects of various methods of compensating for the glucose loss on blood glucose homoeostasis. 5 dialysis-dependent type I diabetics on equal supplies of carbohydrates and insulin received extra glucose in the dialysis fluid and as infusions before and after dialysis. All 3 experimental regimens prevented reduction of the blood glucose level due to dialysis, without any significant differences between them. The choice of method can be made according to the dialysis equipment used.

Adult↗

Reticular formation of the lower brainstem. A common system for cardiorespiratory and somatomotor functions: discharge patterns of neighboring neurons influenced by cardiovascular and respiratory afferents.

Experiments were done in dogs with chloralose-urethane anesthesia. Long-lasting extracellular recordings were made from the medial parts of the reticular formation of the lower brainstem for up to 250 min. The study is based on reactions of 103 neurons. The activities of 2 or 3 neighbouring neurons recorded under identical conditions with one electrode or of neurons recorded with two electrodes at the same time could be changed regularly and synchronously by experimental changes of hemodynamic or ventilatory parameters. Action potentials were separated by amplitude discrimination. Rhythmic pulsatile modulations were proved to be present in 78% of all neurons by post-event-time histograms triggered by the R-wave of the ECG. In the 96 neurons tested 86% changed their activity when arterial pressure was raised by inflating a balloon in the abdominal aorta (79% decreased and 7% increased their activity). In post-event-time histograms triggered by the start of inspiration, 83% of the neurons showed modulations of their activity with respiratory rhythm. Experimental lung inflation decreased the activity in 75% of the tested neurons, while experimental lung deflation activated 47% of the tested neurons. Stimulation of arterial chemoreceptors activated 77% of the tested neurons. It was thus demonstrated that receptors in the cardiovascular and respiratory systems exert an influence on nearly all neurons from which recordings were made in that part of the reticular formation. Arterial baroreceptors and lung stretch receptors revealed a generalized depressing effect on the neuronal activity while chemoreceptors exert a generalized augmenting effect. At different times of recording these neurons did not always react to the same extent to comparable stimulations of afferents.

Action Potentials↗

Reticular formation of the lower brainstem. A common system for cardiorespiratory and somatomotor functions: discharge patterns of neighboring neurons influenced by somatosensory afferents.

Extracellular recordings were made from 103 neurons located in the medial parts of the reticular formation of the lower brainstem of chloralose-urethane anesthetized dogs. Activities of 2 or 3 neighbouring neurons under identical conditions could be recorded with one electrode. In 9 recordings it was possible to register simultaneously up to 5 neurons with two electrodes placed in both halves of the medulla. Action potentials of individual neighbouring neurons were identified by amplitude discrimination. The influences of somatosensory afferents from skin, joints and muscles on neuronal discharge patterns were tested. Responses of single neurons were characterized by multisensory afferent spectra including afferents from various parts of the body. The combinations of afferents converging onto neighbouring neurons were similar, whereas neurons in more distant parts of the medulla revealed different combinations of converging afferents. In long-lasting recordings the influence of somatosensory afferents on the discharge behaviour changed from time to time. When the discharge behaviour was mainly determined by somatosensory afferents, neighbouring neurons were shown to be organized in sub-populations. The results led to the conclusion that in this part of the reticular formation different types of functional organization of the neuronal network are possible. The type of functional organization depends on the actual preponderances of different inputs to the neurons.

Animals↗

Insulin receptor binding and insulin-mediated glucose uptake in type-II-diabetics.

A 5-hour insulin clamp was performed in 7 normal subjects (N) and 6 type-II-diabetics. After a 10-min-priming insulin infusion, a constant infusion of 1.813 micrograms/m2 s.a./min was given to all subjects. Glycemia was kept at fasting levels by a variable glucose infusion. Under these conditions the amount of metabolized glucose (M) has been calculated and served as a measure of insulin-stimulated glucose disposal. M differed markedly between N (35.6 +/- 3.11 mumol glucose/kg b.w./min and diabetics (17.8 +/- 1.17 mumol glucose/kg b.w./min; p less than 0.01) indicating a diminished insulin sensitivity in the latter group. However, M increased slightly but significantly until the end of the study in both groups. Under fasting conditions the mean percent 125I-insulin specifically bound to 3.5 X 10(9) erythrocytes/ml at tracer concentrations was 12 +/- 1.2% and 8.9 +/- 0.9% in N and diabetics, respectively. During insulin infusion specific insulin binding decreased significantly in both groups by 34% and 41%. Thus, the downregulation of insulin binding was similar in both groups and was due to changes in receptor affinity. Assuming that insulin binding to red blood cells mimic that to target cells we conclude that the cause of reduced glucose utilization in type-II-diabetes lies mainly in changes of postreceptor events rather than in receptor binding.

Adult↗

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↗

Diurnal variation in specific insulin binding to erythrocytes.

We studied the insulin binding to erythrocytes during a 24-h period in 11 normal subjects. Compared with 0800 and 1600 h the specific 125I-insulin binding decreased significantly at midnight. These changes were mainly due to alterations in insulin binding affinity rather than a decrease in receptor number. An inverse finding was obtained concerning the plasma insulin levels. In fact, the highest insulin concentrations were observed at midnight. The results suggest that diurnal variations in insulin receptor function occur in response to fluctuations of plasma insulin levels.

Circadian Rhythm↗