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Biomedical subjects

R Hildebrandt

Publications and source records attributed to R Hildebrandt.

At least 19 recordsLinked to original sources
PubMed1997

Histochemical evaluation of placental dipeptidyl peptidase IV (CD26) in pre-eclampsia: enzyme activity in villous trophoblast indicates an enhanced likelihood of gestational hypertensive disorders.

PROBLEM: To determine whether differences in placental dipeptidyl peptidase IV (DPP IV, CD26) activities occurred in hypertensive complicated pregnancies as compared with uncomplicated pregnancies. METHOD: DPP IV activity was detected with H-Gly-Pro-4M2NA as the substrate in placental cryostat sections from 65 patients with gestational hypertension and 67 patients with uncomplicated pregnancies. The graduated intensities of the reaction product in the villous trophoblast were scored semiquantitatively by light microscopy and were related to the relative frequencies of hypertensive disorders (proportional odds model). After detection of enzyme activity, the same tissue samples were homogenized and used for kinetic fluorometric measurements. RESULTS: Enhanced villous trophoblastic DPP IV activity was significantly associated with an increased frequency of proteinuric hypertension in pregnant women (cumulative odds ratio theta1 = 1.6; P < 0.01). CONCLUSION: This study demonstrates for the first time that increased villous trophoblastic DPP IV activity indicates an increased likelihood of the presence and of the severity of hypertensive disorders in pregnancy.

Adult↗
PubMed1997

Hypokalaemia in pregnant women treated with the beta 2-mimetic drug fenoterol--a concentration and time dependent effect.

The effect of tocolytic treatment with fenoterol on plasma potassium concentrations was studied in 83 pregnant women on intravenous tocolytic therapy. Plasma concentrations of fenoterol and potassium were measured simultaneously, the time interval between initiation of therapy and taking the blood sample varying from 2 hours to 100 days. In a subset of 13 patients this blood sample was taken after two hours of therapy and pretreatment potassium concentrations were measured also. Pretreatment potassium concentrations were normal in these 13 patients and declined to 2.88 mmol/L (median) fenoterol concentrations being 320 ng/L through 1164 ng/L. Potassium concentrations measured later than 24 hours after initiation of therapy were all in the normal range corresponding fenoterol concentrations varying from 200 ng/L to 2504 ng/L. The multivariate statistical model for the description of all data showed that the duration of treatment was the only variable which explained the data to a significant extent. This might indicate that tolerance to the potassium lowering effect of fenoterol had developed within 24 hours after initiation of therapy. In the subset of 13 patients pretreatment potassium concentrations were found to be more important in explaining potassium concentrations than fenoterol concentrations at two hours. As we did not observe any adverse events in patients with low potassium concentrations and potassium concentrations were normal within 24 hours, we conclude that hypokalaemia due to fenoterol in the treatment of premature labor is not of clinical concern.

Adrenergic beta-Agonists↗
PubMed1996

Concentration-effect relationship of the positive chronotropic and hypokalaemic effects of fenoterol in healthy women of childbearing age.

OBJECTIVE: To analyse fenoterol-induced tachycardia and hypokalaemia, the most important and most frequent adverse effects of tocolytic therapy with beta 2-adrenoceptor agonists in females of childbearing age. METHODS: The study was performed as a double blind, randomised, placebo controlled, cross over trial. Seven healthy women aged 22-38 y, received intravenous infusions of fenoterol at 3 different rates within the therapeutic range for tocolysis (0.5,1.0, and 2.0 micrograms.min-1) and placebo. The time courses of the plasma concentrations of fenoterol and potassium, and the heart rate were analysed with mixed effects pharmacokinetic-pharmacodynamic (PKPD) modeling using NONMEM. RESULTS: The plasma concentration-time course followed a linear two compartment model. Fenoterol-induced tachycardia was described by a linear concentration-effect model with baseline. The estimated baseline and slope parameters were 78 beats.min-1 and 0.032 beats.min-1.microgram-1.1, respectively. Fenoterol-induced hypokalaemia could be described by a physiological indirect response model including feedback; the Estimated basal plasma potassium concentration was 3.93 mmol.1-1 and the slope factor for the fenoterol-induced relative increase in the efflux of potassium from the extracellular space was 6.22*10(-4) ng.1(-1). CONCLUSION: The estimated population parameters permitted calculation of the expected time course of tachycardia and hypokalaemia in women after the initiation of tocolysis with fenoterol over the clinically relevant concentration range, and prediction of its variability. Based on simulation, our model predicted that a continuous infusion of 2.0 micrograms.min-1 (highest rate examined) would increase heart rate to 113 beats.min-1 at steady state and lower the plasma potassium concentration to 2.77 mmol.1(-1) 1.5 h after beginning the infusion. Thereafter, the plasma potassium concentration would slowly return to normal.

Adrenergic beta-Agonists↗
PubMed1995

Antibodies to cytokeratins bind to epitopes in human uterine smooth muscle cells in normal and pathological pregnancies.

Cytokeratin antibodies have been widely used for the identification of trophoblast cells in the placental bed, following their invasion from the developing conceptus. Their identification centres upon the expression of cytokeratin in epithelial cells, from which trophoblast cells are derived. Our recent observations indicate that this strict relationship may be more complex than was thought. Cryostat and paraffin sections of human decidua and myometrium, taken from the placental bed and the uterotomy cut, were examined immunocytochemically for cytokeratins using ten antibody clones selected to identify different cytokeratin proteins and antigenic epitopes. Biopsy specimens were obtained from normal and pathological pregnancies (pre-eclampsia, fetal retardation, amnioninfection, hysterorrhexis, placenta praevia) at the time of caesarean section (26-41 weeks of pregnancy). Antibodies against nine clones, CAM 5.2, MNF 116, AE1/AE3, CK5, KS-B17.2, CY-90, M20, E3, and 34 beta E12 identified, as expected, syncytial giant cells and mononuclear trophoblasts within the placental bed and glandular epithelial cells throughout the uterus. In addition, they stained numerous fusiform cells that were classified by established criteria to represent smooth muscle cells, both within blood vessels and myometrium. No staining differences were observed between normal and pathological disorders. These results indicate that cytokeratin antibodies CAM 5.2, MNF 116 and AE1/AE3, and other antibodies targeting proteins 8 and 18, cross-react with epitopes expressed in cells other than giant trophoblastic cells and mononuclear trophoblasts in the uterus and, thus, caution has to be used when such antibodies are used for the diagnostic characterization of tissues related to the placental bed.

Actins↗
PubMed1995

Biliary excretion of mezlocillin in patients with hepatic disease.

In three patients with liver disease (2 patients with alcoholic liver cirrhosis and 1 patient with chronic cholangitis) total, renal, biliary and metabolic clearance of the acylureidopenicillin mezlocillin was examined under steady state conditions. Mezlocillin was infused for 6 hours at a constant infusion rate of 10 mg/min. Renal clearance was calculated based on urinary excretion rates. Duodenal perfusion and marker dilution technique was applied to determine biliary excretion rates of the drug. Clearances were estimated by dividing the excretion rate by the respective plasma concentration. Total clearance was calculated by dividing the infusion rate by the plasma concentration. Biliary clearance was markedly reduced in the patients compared to the data of 8 healthy controls (0.65 +/- 0.33 ml/min vs 98.6 +/- 42.5 ml/min). Total and renal clearance were diminished (total clearance: 121.4 +/- 21.6 ml/min vs 286.5 +/- 54.6 ml/min, renal clearance, 65.4 +/- 1.0 ml/min vs 137.6 +/- 32.6 ml/min). In contrast, metabolic clearance was not changed (53.3 23.1 ml/min vs 50.3 +/ 24.2 ml/min). As mezlocillin is well tolerated and has a wide margin of safety we do not recommend reduced dosage. On the contrary, it might even be necessary to increase the dose when treating biliary tract infections in patients with cholestasis in order to assure effective drug concentrations in the bile.

Adult↗
PubMed1994

Fenoterol metabolism in man: sulphation versus glucuronidation.

1. Plasma levels of fenoterol (F) and its conjugate metabolites were determined in healthy female subjects and in pregnant women treated for preterm labour. Sulphate (S) and glucuronide (G) conjugates could be quantified. 2. In the healthy volunteers, AUC of both the metabolites was half that of parent compound (AUC-S/AUC-F: 0.42; 0.14-1.16) (AUC-G/AUC-F: 0.49; 0.18-0.86) during i.v. administration of the drug and was several fold that of parent drug (AUC-S/AUC-F: 116.9; 36.4-353.3, AUC-G/AUC-F: 19.9; 5.1-57.5) after p.o. administration indicating extensive presystemic elimination. 3. In the healthy subjects, the AUC ratio of G:S was 1.1 (0.5-2.6) and 0.16 (0.10-0.27) after i.v. and p.o. administration, respectively, thus indicating that sulphation is the prevailing metabolic pathway in the presystemic elimination. 4. In patients, concentration ratios were used for the analysis. During continuous i.v. treatment, Css-S/Css-F was 3.8 (2.5-4.8) and Css-G/Css-F was 1.5 (0.7-2.1). During p.o. treatment Csstrough S/Csstrough-F was 69.4 (32.1-145.7) and Csstrough-G/Csstrough-F 9.4 (5.6-13.2).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1994

[Importance of measuring blood flow in monitoring pregnancy-induced hypertension and IUGR].

Doppler flow velocimetry of uterine and fetal vessels is carried out in high risk pregnancies. However, there is controversy about the predictive value of elevated resistance indices (RI) with respect of adverse fetal outcome. Therefore we estimated the frequency of elevated RI in uterine and fetal vessels in pregnant women with documented pregnancy induced hypertension (SIH, n = 9), intrauterine growth retardation (IUGR, n = 16) and uncomplicated pregnancies (n = 8). The results of the doppler flow velocimetry were compared to the fetal outcome. Elevated RI were observed in all vessels in the two groups with SIH and IUGR. In contrast, all RI in the control group were found to be in the normal range. The frequency of elevated RI in the a. uterine was slightly but not significantly higher in the SIH group than in the IUGR group. Approximately 50% of the infants of the groups with SIH and IUGR were born prematurely. However, in all but 4 infants apgar score and pH of cord blood were in the normal range. Decision for premature delivery in the IUGR group were mostly based on elevated RI. It is concluded that this may have led to delivery before fetal decompensation occurred and thus may have had a positive effect on fetal outcome.

Adult↗
PubMed1993

Pharmacokinetics of fenoterol in pregnant and nonpregnant women.

The pharmacokinetics of the beta 2-adrenergic drug fenoterol, which is used as a tocolytic agent in pregnancy, has been investigated in pregnant (n = 9) and nonpregnant (n = 5) women during a constant rate intravenous infusion. Clearance and mean residence time were found to be 1990 (1879/2220; Median, Q25/Q75) ml/min and 9.2 (8.0/14.0) min in the pregnant and 2126 (1915/2130) ml/min and 16.6 (16.5/32.1) min in the nonpregnant women, respectively. In addition, fenoterol clearance was estimated in 88 women from a single blood sample collected at steady state during IV therapy and the effect of gestational age on clearance was studied. Clearance displayed large interindividual variation. There was no apparent correlation between clearance and gestational age. We conclude that there is no need to adjust the dose on pharmacokinetic grounds in the course of pregnancy.

Adult↗
PubMed1992

The pharmacokinetics of the beta 2-adrenoceptor agonist fenoterol in healthy women.

We have studied the pharmacokinetics of fenoterol in healthy women during and after a 3 h intravenous infusion of different doses within the therapeutic range for tocolysis (0.5 microgram.min-1, 1.0 micrograms.min-1, and 2.0 micrograms.min-1). A specific and sensitive radioimmunoassay was used for the determination of fenoterol. For compartmental analysis the plasma concentration time data were fitted with the TOPFIT program, assuming two exponentials. The total clearance of fenoterol increased with dose (1299 ml.min-1 at 0.5 microgram.min-1, 1483 ml.min-1 at 1.0 micrograms.min-1, and 1924 ml.min-1 at 2.0 micrograms.min-1), as did the apparent volume of distribution (from 49 l at the lowest to 85 l at the highest dose). In contrast, the apparent half-lives were not dose-dependent, with t1/2.lambda 1 4.8 min and t1/2.lambda z 52 min.

Adult↗
PubMed1992

Improvement of metabolic control and changes of fatty acid composition do not alter platelet aggregability and thromboxane production in type 2 diabetes mellitus.

To evaluate whether improvement of metabolic control or changes in fatty acid composition of serum lipids may alter thromboxane (TXB2) formation and platelet function we followed up 25 newly diagnosed type 2 diabetics without angiopathy for about 6 months. Improvement of metabolic control was associated with significant decrease in total cholesterol (C), HDL-C, LDL-C, triglycerides (TG) and ratios of total C/HDL-C and LDL-C/HDL-C, respectively. Palmitic acid of TG and phospholipids decreased significantly whereas linoleic acid increased in the two serum lipids. The ADP-induced platelet aggregability and sensitivity were not altered. There was even no effect on TXB2 synthesis capacity of clotting whole blood during 6 months of treatment. Platelet aggregability and TXB2 formation were not correlated to the degree of metabolic control, nor was there any correlation to serum lipids and their fatty acid composition.

Adult↗
PubMed1991

Thromboxane production and platelet aggregation in type 2 diabetes mellitus without vascular complications.

Diabetic individuals frequently have platelet hyperaggregability and increased thromboxane (TXB2) production. To evaluate whether improvement of metabolic control or changes in fatty acid composition of serum lipids might alter thromboxane (TXB2) formation and platelet function, we followed up 25 newly diagnosed type 2 diabetics without angiopathy for about 6 months. Improvement of metabolic control (HbA1, fell from 12.0 +/- 0.3 to 9.0 +/- 0.3%; p less than 0.01) was associated with significant decrease in total cholesterol, triglycerides, and ratios of total cholesterol/HDL-cholesterol and LDL-cholesterol/HDL-cholesterol. Palmitic acid of phospholipids decreased significantly, whereas eicosapentaenoic acid increased. Regardless of this, the ADP-induced platelet aggregability and sensitivity were not altered. There was no effect whatever on the TXB2 synthesis capacity of clotting whole blood (204.9 +/- 25.0 vs 222.8 +/- 32.0 ng/ml) over 6 months of treatment. Platelet aggregability and TXB2 formation were not correlated to the degree of metabolic control, nor were there any correlations to serum lipids and their fatty acid composition. Thus, we are tempted to speculate that glucose metabolism in diabetes itself does not affect platelet aggregation or TXB2 formation in type 2 diabetes mellitus.

Adult↗
PubMed1990

[Multiple reuse of disposable material for insulin injection without resterilization].

Of 123 type I diabetics 306 one-way syringes and canules, respectively, were repeatedly used for the insulin injection in the domestic milieu (altogether 4,157 injections). The average duration of application was 29 days (2-296), the average number of injections 51 (4-422). Of 81% of the patients no immediate cleaning was made. No local reactions appeared at the sites of injection. At the end of the use all injection materials were free from bacterial contaminations (determination of the germ number in the lumen of the syringes and canules). One-way material can repeatedly be used by one and the same diabetic for the insulin injection in the domestic milieu, observing a normal personal hygiene regimen (1 week or 30 injection in uninterrupted sequence). It is not necessary to perform an intermediate cleaning of the materials.

Colony Count, Microbial↗
PubMed1990

[Experiences with conversion from MC-insulin NOVO to L-insulin S.N.C. of insulin dependent diabetic patients].

After a circa 10-year therapy with MC-insulin NOVO 12 diabetics were changed to the chromatographically purified insulins L-insulin S.N.C. and insulin S.N.C. of the nationally-owned enterprise Berlin-Chemie. 3 and 6 months, respectively, ago after the ambulatory change the patients were metabolically, immunologically, hormonally and clinically characterized. Profiles of blood glucose, value of glycaemia and HbA1 also lipid parameters, creatinine values, residual B-cell function, blood pressure and ophthalmologic state did not show any significant differences to the initial values after change to S.N.C.-insulins. Insulin-antibody level (9.5%-9.4%-9.7%) and insulin need (0.48 IU/kg-0.46 IU/kg-0.48 Iu/kg) also remained unchanged. Local reactions were not observed. Under the condition of a permanently good quality of the S.N.C.-insulins (purity and stability of the preparations) the application of chromatographically purified insulin of the firm Berlin-Chemie with comparable therapeutic success as in insulin MC NOVO is possible in a large part of the patients.

Adult↗
PubMed1990

[The microbial count of insulin multiple-dose containers].

In accordance with the Pharmacopoeia of the GDR, from multiple-dose containers containing injection preparations with preservatives added such preparations may be repeatedly withdrawn up to 72 h after opening these containers. Exempted from this limitation are multiple-dose containers containing insulin injection preparations repeatedly used by diabetics for self-injections. Microbiological tests were to contribute to clearing the question whether the period of using these insulin multiple-dose containers can be provided to be maximally 30 d after first use.

Colony Count, Microbial↗