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Biomedical subjects

R Hildebrandt

Publications and source records attributed to R Hildebrandt.

At least 37 records · Page 2Linked to original sources
PubMed1989

[Conventional insulin treatment and treatment using multiple injections in diabetes mellitus].

The relationship between development of late diabetic complications and the degree of diabetic control is discussed and thus also the indications for intensive insulin treatment. To promote improved understanding of the basis for treatment with multiple insulin injections, regulation of glucose metabolism in normal individuals is reviewed. The practical management in different insulin regimes and the advantages and disadvantages of these are mentioned. In particular, problems in connection with the "early morning phenomenon", postprandial hyperglycaemia and day-to-day variations in insulin absorption are emphasized.

Blood Glucose↗
PubMed1988

Is there a relationship between metabolic control and glucose concentration in breast milk of type 1 (insulin-dependent) diabetic mothers?

We studied glucose concentration of breast milk of nursing diabetic mothers and its possible relationship to the quality of metabolic control. Eleven Type 1 (insulin-dependent) diabetic mothers and 11 age-matched control subjects were included in the study. Although a near-normoglycemic control of diabetic mothers was accomplished by intensified insulin treatment, the HbA1 value was significantly higher in comparison to non-diabetic mothers (8.1 +/- 0.9% versus 6.2 +/- 0.5%; p less than 0.01). Regardless of this, the glucose concentration of breast milk did not differ between diabetic mothers and that of non-diabetic women (0.68 +/- 0.50 mmol/l versus 0.66 +/- 0.55 mmol/l). No correlation exists between glucose concentration of breast milk and relevant blood glucose concentration as well as glycosylated haemoglobin A1 of the mother. In conclusion, our data support the view that breast-feeding of infants of diabetic mothers is not associated with an increased offer of glucose and thus not being of importance as a possible mechanism to sustain a hyperinsulinemic state in the newborns.

Blood Glucose↗
PubMed1988

Relationship between fatty acid pattern and platelet aggregation in long-term insulin-dependent type I diabetics.

We investigated triglycerides, total cholesterol, HDL cholesterol, the fatty acid patterns of serum triglycerides, cholesterol esters and phospholipids in relation to the ADP induced platelet aggregation in 34 long-term insulin-dependent diabetic patients with an extremely long diabetes duration of about 40 years. The concentrations of triglycerides, total cholesterol and HDL cholesterol of the patients did not differ from those of an age-matched non-diabetic control group. In the insulin-dependent diabetics the percentages of arachidonic and eicosapentaenoic acid in both serum cholesterol esters and phospholipids were decreased in comparison with control subjects. No difference was observed with respect to the ADP induced platelet aggregation between long-term diabetics and controls. The findings demonstrate that type I diabetic patients with an extremely long duration of diabetes are not characterized by increased serum lipids or platelet aggregation, both being well known risk factors for macroangiopathy. However the decreased portions in eicosanoid synthesis precursors may indicate a disturbed fatty acid metabolism.

Cholesterol↗
PubMed1987

Influence of theophylline on the renal clearance of erythromycin.

The influence of theophylline on the kinetics of erythromycin was studied in 11 healthy subjects who received both drugs intravenously in therapeutic doses. Total clearance, terminal half-life and volume of distribution of erythromycin were not altered by concomitant theophylline treatment. However, renal clearance of erythromycin was enhanced by theophylline treatment (86.0 +/- 81.1 ml/min vs. 32.5 +/- 15.9 ml/min, with vs. without theophylline). Theophylline also altered urinary flow rate (4.7 +/- 1.6 ml/min vs. 1.9 +/- 1.2 ml/min, with vs. without theophylline) whereas fluid intake was identical (125 ml/h) as well as the pH of the urine (pH 6.5). The possible explanation that theophylline is acting via enhancing urinary flow rate, which reduced tubular reabsorption of erythromycin, has been ruled out by the findings of an additional trial done in 6 out of the 11 subjects. In this trial, renal clearance of erythromycin was not influenced by enhanced urinary flow rate (7.2 +/- 1.9 ml/min) which was due to high fluid intake (500 ml/h) whereas the pH of the urine was kept at 6.5 as in the first part of the study. When other mechanisms to explain the observed interaction were discussed taking into account our published results on theophylline kinetics influenced by concomitant erythromycin administration, the most likely explanation for our finding seems to be the interaction between erythromycin and 1-methyluric acid, one of the theophylline metabolites.

Adult↗
PubMed1987

The influence of cod-liver oil diet on various lipid metabolism parameters, the thromboxane formation capacity, platelet function and the serum MDA level in patients suffering from myocardial infarction.

The influence of an eicosapentaenoic-acid-rich diet, containing 8.1 g cod-liver oil, given daily for two weeks on various parameters of lipid metabolism, the thromboxane formation capacity, platelet function and the serum MDA level was studied in 16 patients with myocardial infarction. The 18:2, 20:3 and 20:4 fatty acid portions of serum phospholipids were significantly decreased, whereas the 20:5 and 22:6 portions were significantly elevated. Serum total cholesterol, LDL cholesterol and the thromboxane formation capacity were significantly increased. Serum triglycerides, HDL cholesterol, the prostacyclin blocking activity of LDL, and several parameters of platelet function were unchanged, the platelet count was significantly depressed. As compared to those of healthy persons, the serum MDA levels in myocardial infarction patients were significantly increased both before and after cod-liver oil ingestion. A possible correlation between the elevated serum levels of MDA and total cholesterol, LDL cholesterol as well as thromboxane formation capacity and the cod-liver oil treatment in patients with myocardial infarction is discussed.

Cholesterol↗
PubMed1986

Measurement of insulin during isolation and purification from animal pancreas. A comparison of radioimmunoassay, radioreceptor assay and in-vivo bioassay.

For the purpose of monitoring the yield of the insulin extraction procedure from animal pancreas three methods of insulin determination were compared, i.e. the mouse convulsion test, a radioreceptor assay (RRA) on rat fat cells and a radioimmunoassay (RIA) which was especially laid out for high insulin concentrations. In samples containing actually insulin in general all three methods provided comparable results. Notable differences were only found in proinsulin-containing material. Because of its simplicity and high reproducibility as well as the good agreement of its results with those obtained with the other assays, the RIA turned out to be the most suitable assay. On the other hand, the RRA should be useful in detecting molecular differences between the investigated insulin-like preparations and standard insulin.

Animals↗
PubMed1985

Pharmacokinetics of ceftizoxime.

The kinetics of ceftizoxime, a newly developed cephalosporin, were evaluated in 6 healthy subjects, with respect to its excretory pathways especially by the biliary route. Total, renal and biliary clearance were determined at two different steady states. Steady state was achieved by constant intravenous infusion (604.1 mg/h) over 6 h after an initial loading dose (750 mg); 1.5 h after discontinuation of that infusion, a further infusion was commenced at a lower rate (284 mg/h) over 3 h, the second steady state being reached 0.5 to 1.0 h later. The drug was mainly excreted by the kidneys (56.7 to 92.9% of the dose). Biliary excretion, measured by the duodenal perfusion and marker dilution technique, was low (0.2 to 7.8% of the dose). Urinary and biliary excretion as well as total clearance were not dose-dependent. However, there was pronounced interindividual variation in total (35.2 to 236 ml/min) and renal clearance (10.6 to 208 ml/min), which could both be explained by varying interindividual urinary flow rates (mean flow rate: 0.99 ml/min to 3.14 ml/min). Intraindividual variation in renal clearance was less pronounced, but in the same subject changes in renal clearance were correlated with changes in urinary flow rate. From the varying renal clearance, which exceeded the glomerular filtration rate at high urinary flow rates and was below it at low urinary flow rates, it can be concluded that, in addition to glomerular filtration, tubular secretion and tubular reabsorption are involved in the renal excretion of ceftizoxime.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Pharmacokinetics of sulphinpyrazone and its major metabolites after a single dose and during chronic treatment.

The pharmacokinetics of sulphinpyrazone and its major metabolites (sulfide, sulfone, p-hydroxysulfone and p-hydroxy-sulphinpyrazone) were investigated in 9 volunteers after a single oral dose as well as after chronic treatment for 23 days. Chronic administration of sulphinpyrazone, in comparison with a single oral dose, led to significant changes in plasma AUC (115.86 to 42.90 mg/l . h), in renal clearance (1.06 to 1.80 l/h), in hepatic intrinsic clearance (319.0 to 598.0 l/h), and in the unbound fraction in plasma 1.15 to 1.69%) and in tissue (2.73 to 1.31%). The volume of distribution changed from 20.24 to 52.04 l. The steady state concentrations predicted from the single dose were significantly higher than the values found after chronic treatment. The results suggest that sulphinpyrazone induces its own metabolism. The metabolism of the sulfone, p-hydroxysulfone and the p-hydroxy-sulphinpyrazone to further degradation products was also induced. Chronic treatment with sulphinpyrazone reduced the plasma AUC of the sulfide and caused a decrease in its elimination half-life (20.9 to 14.3 h). Since considerable amounts of the sulfide are formed in the G.I. tract, it is suggested that besides the induction of metabolism, bacteria which reduce sulphinpyrazone to the sulfide may also be responsible for the observed pharmacokinetic changes.

Adult↗
PubMed1984

Lack of clinically important interaction between erythromycin and theophylline.

In 11 healthy volunteers the kinetics of theophylline and the plasma levels and the urinary excretion of its metabolites were studied before and after treatment with erythromycin for 10 days. Theophylline was administered as an intravenous bolus injection (280 mg) followed by a constant intravenous infusion (23.8 +/- 4.1 mg/h) for 6 hours. The total clearance of theophylline at steady-state (63.4 +/- 9.9 vs 63.8 +/- 14.4 ml/min, before vs after erythromycin treatment) and the elimination half-life after cessation of the infusion (6.7 +/- 2.6 vs 7.5 +/- 1.8 h, before vs after treatment) did not change during the treatment with erythromycin. No difference in the formation of metabolites before and after treatment with erythromycin was detected; the findings in urine were 40.4 +/- 5.0 vs 42.1 +/- 5.4% 1,3-dimethyluric acid, 29.6 +/- 4.6 vs 30.1 +/- 5.9% 1-methyluric acid and 13.4 +/- 3.5 vs 12.5 +/- 2.2% 3-methylxanthine before and after erythromycin treatment, respectively. It is concluded that a clinically relevant interaction between erythromycin and theophylline does not occur.

Adult↗
PubMed1984

Correlation between the pharmacokinetics and pharmacodynamics of dopamine in healthy subjects.

The pharmacokinetics and the pharmacodynamic action of dopamine were investigated in 5 healthy subjects. Dopamine was given in different doses (200, 400 and 800 micrograms/min) by constant intravenous infusion over 90 min. In order to control the influence of the procedure on the measured parameters the subjects also received a similar infusion of saline. Dopamine, noradrenaline and adrenaline levels in plasma were followed for up to 6 h after the infusion, and arterial pressure and heart rate were monitored. Dopamine reached a steady state level within 15 to 30 min after commencement of the infusion; the steady state levels averaged 36.5 micrograms/l at 200 micrograms/min, 73.8 micrograms/l at 400 micrograms/min and 207 micrograms/l at 800 micrograms/min. The corresponding total clearances were 5.81/ min, 5.51/min and 3.91/min suggesting non-linear kinetics. The kinetics could not be described by compartmental model. Noradrenaline and adrenaline levels were found to be elevated during infusion of dopamine. Noradrenaline had returned to its pretreatment level within 15 to 30 min after cessation of the infusion, whereas the adrenaline level did not return to the pretreatment value within the observation period. Heart rate was increased by the dose of 400 micrograms/min, and the systolic and mean arterial pressures were elevated, whereas distolic blood pressure remained unchanged. Elevated systolic blood pressure was better correlated with plasma dopamine than with noradrenaline concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1984

Effect of insulin suppositories in type I diabetic patients (preliminary communication).

Eight type I diabetic patients received a subcutaneous injection of 10 IU regular insulin, or--after a one week interval--a suppository containing 75 IU crystalline insulin, the surfactant Brij 58, and the basic mass. In all patients there was a disease in blood glucose (onset after 20 min, maximum effect after 50 min, end of the effect after 90 min), and the plasma IRI level increased. However, the effect was attenuated in relation to the control test employing s.c. administration. The ratio of subcutaneous to rectal doses required to achieve the same effect was between 1:18 and 1:26.

Adult↗
PubMed1984

Influence of a cod liver oil diet in diabetics type I on fatty acid patterns and platelet aggregation.

The influence of an eicosapentaenoic acid rich diet containing only 6,8 g cod liver oil daily for 2 weeks in 20 type I diabetics on fatty acid pattern in serum, platelet aggregation and thiobarbituric acid-reactive substances in serum were studied. There were increases in eicosapentaenoic acid portions in triglycerides, cholesterol esters and phospholipids of serum. This was associated with an inhibition of the platelet hyperaggregation, whereas platelet hyporeactivity is shifted to normal. Hyperreactivity of platelets from diabetics may be caused by enhanced TXA2 formation in comparison to healthy humans (1). On the other hand, diets rich in eicosapentaenoic acid inhibit platelet aggregation in healthy Volunteers (2,3). Therefore we investigated the dietary effect of relatively low doses of cod liver oil in diabetics type I on the eicosapentaenoic acid/arachidonic acid balance.

Adult↗
PubMed1983

Lack of interaction between the tetracyclic antidepressant maprotiline and the centrally acting antihypertensive drug clonidine.

The well known interaction between tricyclic antidepressants and the centrally acting antihypertensive drug clonidine, namely impairment of the antihypertensive effect of clonidine, is thought to be related to blockade of noradrenaline uptake or competition at central alpha-receptors. The tetracyclic antidepressant maprotiline has been shown to be a potent inhibitor of noradrenaline uptake and it might, therefore, interfere with the antihypertensive action of clonidine. The possible interaction of clonidine and maprotiline was studied in 8 healthy subjects using doses in the therapeutic range. The study followed a double-blind, cross over design, in which clonidine alone (0.3 mg p.o.), clonidine (0.3 mg p.o.) plus maprotiline (100 mg in 4 divided doses over 22 h), maprotiline alone (100 mg in 4 divided doses over 22 h) and placebo were given by the double-dummy technique. Several pharmacodynamic parameters were measured for 12 h after administration of the drugs (supine and erect blood pressure, heart rate, saliva production and sedation). Concurrent administration of maprotiline did not alter the effect of clonidine and neither the size nor the time of the maximal response after clonidine were influenced by maprotiline. It is concluded that [1] blockade of noradrenaline uptake is not associated with the interaction of tricyclic antidepressants and clonidine, and [2] maprotiline should be preferred to tricyclic antidepressants in hypertensive patients on clonidine therapy if a concomitant depressive illness has to be treated.

Adult↗
PubMed1983

Effect of single and multiple doses of sulphinpyrazone on antipyrine metabolism and urinary excretion of 6-beta-hydroxycortisol.

Sulphinpyrazone decreases the plasma clearance of tolbutamide and S-warfarin and increases the clearance of R-warfarin, theophylline and antipyrine. In order to determine whether sulphinpyrazone is an inducer or inhibitor or both of oxidative drug metabolism, antipyrine and its metabolites as well as 6-beta-hydroxycortisol were measured in urine before, 24 h and after 23 days of chronic administration of sulphinpyrazone (4 X 200 mg/day). During chronic treatment sulphinpyrazone increased the ratio of 6-beta-hydroxycortisol to the 17-hydroxycorticosteroids by 70% (p less than 0.02). The renal clearance of the main oxidative metabolites of antipyrine (4-hydroxyantipyrine, 3-hydroxymethylantipyrine and norantipyrine) were increased after sulphinpyrazone (p less than 0.02). Except for norantipyrine, no change in total excretion of antipyrine and its metabolites occurred after 24 h or after 23 days. It is concluded that sulphinpyrazone induces the enzymes which metabolize antipyrine and cortisol.

Adult↗
PubMed1983

Intestinal absorption of levodopa in man.

In four healthy subjects the intestinal absorption of levodopa (l-dopa) was investigated by measuring the plasma concentration of the amino acid following the administration of l-dopa at three different sites in the small intestine. In order to minimize presystemic clearance of l-dopa, the subjects were pretreated with the peripheral decarboxylase inhibitor benserazide 3 X 50 mg every 8 h on the previous day and 1 X 50 mg 2 h prior to administration of the l-dopa. L-dopa 100 mg dissolved in 0.05 N HCl and 50 mg benserazide dissolved in 0.05 N HCl were coadministered. Under these conditions no difference in tmax, cmax or AUC of l-dopa was observed between administration of the drug into the proximal or the distal part of duodenum, or into the upper part of jejunum. The results indicate that in healthy subjects, during inhibition of peripheral decarboxylase, the rate and extent of l-dopa absorption does not differ at any site in the upper small intestine.

Adult↗
PubMed1983

Non-linear elimination processes of theophylline.

After intravenous and oral administration of theophylline to four healthy subjects, the plasma concentration-time curve of theophylline could be described by linear pharmacokinetics, although total clearance in all subjects decreased when the dose was increased; the doses were theophylline 193.2 mg and 386.4 mg i.v. and 161 mg and 322 mg p.o. Total clearance was 65.5 +/- 11.3 ml/min. Renal clearance changed from 15.2 +/- 9.5 ml/min in the first two hours after administration to 4.9 +/- 5.5 ml/min between 16 and 24 h (p less than 0.001). 1,3-dimethyluric acid (DMU), the major metabolite of theophylline, was determined in urine and in plasma. The renal clearance of DMU was constant at 496.7 +/- 180 ml/min. There was some evidence that at high plasma concentrations of theophylline the formation of DMU might be a zero-order process. The renal excretion rate of 1-methyluric acid (1-MU) paralleled that of DMU, which is in accordance with the assumption that DMU is demethylated to 1-MU. 3-methylxanthine (3-MX) was excreted in urine at a constant rate over 10 h, the rate being equivalent to the dose, which is contrary to the assumption of Michaelis-Menten-kinetics. 3-methyluric acid was found to be a minor metabolite of theophylline and 1-methylxanthine (1-MX) could not be detected. The cumulative amounts excreted in urine, expressed as a percentage of the dose and corrected for molecular weight, were theophylline 16.6 +/- 6.5%, DMU 44.3 +/- 7.0%, 1-MU 24.3 +/- 4.8%, 3-MX 12.9 +/- 3.4% and 3-MU 2.2 +/- 1.8%.

Adult↗