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Biomedical subjects

U Siekmann

Publications and source records attributed to U Siekmann.

At least 19 recordsLinked to original sources
PubMed1999

Effects of hyperbaric and hyperoxic conditions on the disposition of drugs: theoretical considerations and a review of the literature.

1. Hyperbaric or hyperoxic or both conditions may affect the disposition of drugs by (1) changes in the catalytic activity of drug metabolizing enzymes, (2) hemodynamic changes and (3) changes in membrane permeability, affecting drug distribution. 2. In isolated microsome preparations from rat liver, the metabolism rate of aniline, but not of amidopirin, is reduced by hyperoxia. In vivo, the clearance of salicylic acid is enhanced in the dog at 2.8 ATA and 100% O2, but not at 6 ATA and air, for reasons that are still unknown. The disposition of theophylline, pentobarbital or pethidine is not affected in dogs by hyperbaric or hyperoxic conditions. 3. In human volunteers, hyperbaric or hyperoxic or both conditions do not affect the disposition of gentamycin (2.4 bar, 100% O2), caffeine or lidocaine (2.5 bar, 100% O2). 4. In conclusion, a single exposure to hyperbaric or hyperoxic conditions does not seem to affect single-dose pharmacokinetics of drugs eliminated by the kidney (gentamycin) or by the liver with a capacity-limited clearance (pentobarbital, theophylline, caffeine) or with a perfusion-limited clearance (pethidine, lidocaine). The enhancement of salicylic acid clearance in dogs under hyperoxic conditions remains unclear.

Animals↗
PubMed1997

Caffeine pharmacokinetics during hyperbaric hyperoxia in humans.

The effect of hyperbaric hyperoxia on the pharmacokinetics of caffeine was investigated in human volunteers. Some 600 ml of coffee were administered to 2 volunteers and blood samples were serially collected for 24 h. The volunteers entered a hyperbaric chamber 2.5 h following coffee ingestion for a total period of 110 min (0.25 MPa, alternating 100% O2-breathing for 20 min and air breathing for 5 min). The concentrations of caffeine in serum was determined by high pressure liquid chromatography. The caffeine amount ingested was determined by analyzing an aliquot of the coffee beverage. Data were analyzed assuming linear kinetics and an open one-compartment model. Effects of hyperbaric hyperoxia on caffeine disposition were investigated using a runs test. Moreover, a one-population t-test was applied to residuals, separately for data from the initial normobaric period, the hyperbaric period and the terminal normobaric period. Pharmacokinetic parameters were similar to established literature data on caffeine [Volunteer 1: maximal concentration (Cmax: 6.13 mg.L-1 at Tmax: 55 min, half-time of elimination (T1/2: 180 min, total clearance (Cl): 3.41 ml.min-1.kg-1; volume of distribution (Vd: 0.88 I.kg-1; Volunteer 2: Cmax: 6.23 mg.L-1, Tmax: 94 min, T1/2: 283 min, Cl: 1.90 ml.min-1.kg-1, Vd: 0.77 L.kg-1). The runs test as well as the analysis of residuals gave no evidence for alterations of caffeine disposition by hyperoxia (p > 0.05). The pharmacokinetics of caffeine do not seem to be influenced in a clinically relevant way in humans during a stay for 100 min at 0.25 MPa, alternating 100% O2 and air breathing.

Adult↗
PubMed1989

Hemodynamic and hemorheological profiles in women with proteinuric hypertension of pregnancy and in pregnant controls.

We obtained blood samples from 52 patients with pre-eclampsia and from 40 pregnant controls for measurement of plasma urate levels, hematocrit, white cell count and various hemorheological parameters. We also used impedance cardiography to measure cardiac output in both groups and from the results derived values for total peripheral resistance and oxygen transport. Central venous pressure was measured with a superior vena cava catheter in patients with pre-eclampsia but not in controls. Women with pre-eclampsia had significantly lower cardiac output and central venous pressure when compared with a control group. A modest correlation was observed between central venous pressure and cardiac output. The majority of pre-eclamptic patients had significantly raised hematocrit, leucocyte count, uric acid and red cell aggregation. Red cell deformability was significantly decreased in patients with pre-eclampsia. Most patients with severe pre-eclampsia (BP diast. greater than 100 mmHg) had a low Antithrombin III and colloid osmotic pressure level. The leucocyte count was raised when compared with the women with moderate pre-eclampsia. Oxygen delivery was reduced in patients with pre-eclampsia because of impaired rheological properties of their blood.

Cardiac Output↗
PubMed1989

[Seminar: electronic data processing in gynecology and obstetrics].

Several possible procedures were discussed for computerizing clinical research and basic documentation. All approaches were evaluated with regard to available performance and installation effort. Additionally examples for personal computer aided data collection in the field of perinatology, oncology, endocrinology and expert systems were presented.

Electronic Data Processing↗
PubMed1989

Decreased myometrial beta-adrenoceptors in women receiving beta 2-adrenergic tocolytic therapy: correlation with lymphocyte beta-adrenoceptors.

We have determined simultaneously the density of beta-adrenoceptors in human myometria (by (-)-[125I]iodopindolol binding) derived from 36 women undergoing cesarean section and in the corresponding circulating lymphocytes (by (-)-[125I]iodocyanopindolol binding). In myometrial membranes about 80% to 85% of the beta-adrenoceptors were of the beta 2-subtype. The density of myometrial and lymphocyte beta-adrenoceptors in women treated with the beta 2-adrenoceptor agonist hexoprenaline to prevent preterm labor was about 65% to 70% lower than that in nontreated women. Concomitantly, in hexoprenaline-treated women the 10 mumol/L isoproterenol-evoked increase in lymphocyte cyclic adenosine monophosphate content (as index for lymphocyte beta-adrenoceptor responsiveness) was diminished to a similar extent. Combining all data resulted in a significant positive correlation between myometrial and lymphocyte beta-adrenoceptor densities (r = 0.7303; n = 36; p less than 0.001). It is possible that determination of beta-adrenoceptor function in circulating lymphocytes may be a useful model to monitor myometrial beta-adrenoceptor changes during tocolytic therapy.

Adolescent↗
PubMed1989

[Changes in hemodynamic values in various phases of pelviscopy].

In 57 patients the effects of various stages during routine laparoscopy (induction of anaesthesia, intraabdominal insufflation of carbon dioxide, changes in body position) on cardiac performance were investigated. For the measurement of cardiac output we used the noninvasive thoracic impedance cardiography. After induction of anaesthesia and with terminated CO2 insufflation cardiac index significantly decreased compared to the reference values prior to surgical intervention (3.21 L/m2 vs. 1.96 L/m2; p less than 0.0001). At the end of laparoscopy in Trendelenburg position there was a slight increase in cardiac index with 2.26 L/m2. After the patients had been returned to the horizontal position and the abdomen was then deflated cardiac index almost reached the values at the beginning of laparoscopy. We demonstrated a high reproducibility in cardiac output measurements using impedance cardiography when comparing the respective values 24 hours prior to laparoscopy and those results investigated 24-48 hours after the surgical intervention. With regard to clinical situations of hypovolemia, f.e. ruptured ectopic pregnancies it is evident that the described alterations in cardiac performance should be considered.

Adolescent↗
PubMed1986

[Prenatal sonographic diagnosis of abnormalities and the significance of prepartum therapeutic procedures].

Between 1981 and October 1985, prenatal ultrasound examinations revealed 19 malformations of the central nervous system, 13 intestinal malformations, 15 malformations of the urogenital tract, four non-immunological cases of hydrops fetalis, two sacral teratomas and one cardiac malformation. In only one of eleven cases of hydrocephalus were all preconditions fulfilled for considering an intra-uterine ventriculo-amniotic shunt insertion. In bilateral obstructive uropathy the dynamics of amniotic fluid volume both before and after intra-amniotic administration of an infusion is decisive for any further prognostic assessment. There are marked differences regarding the neonatal survival rate between the various organ-specific malformations (gastro-intestinal: 31%; hydrocephalus: 55%; obstructive uropathy: 89%). Personal experience suggests that there are only a few cases requiring intra-uterine, predominantly invasive, treatment. The value of prenatal ultrasound examination lies mainly in early diagnosis and the resulting choice of subsequent obstetric measures. Of particular importance is an interdisciplinary collaboration with specialists in allied fields.

Congenital Abnormalities↗
PubMed1986

Simultaneous investigations of maternal cardiac output and fetal blood flow during hypervolemic hemodilution in preeclampsia--preliminary observations.

In pre-eclampsia hemodynamic alterations are characterized by a lack of plasma volume expansion and a raised peripheral vascular resistance. For the compensation of plasma volume deficit and to restitute blood fluidity the therapeutic use of plasma volume expanders (f.e. low molecular dextran) is recommended. Several groups (Goodlin et al., Cloeren et al., Heilmann et al., Seghal et al., Schröck) have demonstrated benefitial effects on fetal status and development in the course of hypervolemic hemodilution in preeclampsia. This therapeutic procedure presumes the continuous surveillance of maternal hemodynamics to early recognize heart insufficiency or fluid overload in the lungs. We use the noninvasive thoracic impedance cardiography for continuous monitoring of maternal heart performance. The effect of hypervolemic hemodilution on fetal circulation has not been quantitatively investigated yet. Meanwhile pulsed doppler ultrasonography offers the possibility of estimating quantitative changes on fetal blood flow. We used both noninvasive techniques--thoracic impedance cardiography and pulsed doppler imaging system--for the simultaneous evaluation of maternal and fetal hemodynamic parameters during hypervolemic hemodilution. This preliminary report summarizes the investigations in 5 patients with pre-eclampsia (mean arterial blood pressure greater than or equal to 103.3 mm Hg, hemoconcentration with elevated hematocrit levels greater than or equal to 38%). The patients received an infusion of 500 ml dextran 40 over a period of exactly 60 minutes. The simultaneous measurements of maternal and fetal cardiovascular parameters were performed in 15-minutes intervals during dextran application and 15 minutes (p 15), 30 minutes (p 30) and 60 minutes (p 60) after the end of infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

[Hexoprenaline--a new tocolytic for treatment of premature labor].

Hexoprenaline is a selective beta 2-mimetic drug used in tocology for the prevention of premature labor and immature birth. From clinical application of the drug in bronchospasm therapy its selectivity, which is due to the elongated nitrogen substituent, is well-known. Because of the relatively small stimulation of cardiac beta 1-receptors the side-effects related therewith are less pronounced than with other beta-mimetics. The extent of tachycardia depends on the initial sympathomimetic condition of the patients. The success rate for hexoprenaline tocolyses is 34-78%, dependent on the initial tocological condition. The advantage of hexoprenaline compared with other tocolytics on the basis of experience made so far seems to relate to the smaller increase in chronotropy and the better tolerability.

Female↗
PubMed1984

[Maternal and fetal hemodynamics under simultaneous beta stimulation and beta1 blockade in a tocolysis model. Considerations on status of the neonatal beta receptor and transplacental passage of metoprolol].

This report summarizes the clinical experiences in the treatment of preterm labor using the combination of hexoprenaline and the beta 1-antagonist metoprolol. We found a dose dependency in the antagonism of positive inotropic effects primarily induced by the beta-stimulator hexoprenaline. To verify the pharmacological properties of metoprolol in transplacental passage we evaluated the plasma concentration of metoprolol in umbilical cord blood. There is quite a low concentration of the beta-blocker nearly 24 h after the last course of administration. The beta 2-receptor density--determined by (+/-)-125-iodocyanopindolol (ICYP) binding--and beta 2-receptor responsiveness--assessed by cyclic AMP response to isoprenaline stimulation--in lymphocytes derived from neonatal blood were also investigated. These results were compared with identical investigations in adult lymphocytes. The results indicate that in neonates beta 2-receptor density and responsiveness is significantly diminished in comparison to the adult controls. The present investigations induce a new concept for the estimation of concomitant fetal cardiovascular reactions under maternal beta-blockade.

Adrenergic beta-Agonists↗
PubMed1984

[Effect of metoprolol on the flow properties of blood].

In the present article the interaction of 1- isopropylamino-3-[4-(2-methoxyethyl)-phenoxy]-2-propanol (metoprolol, Beloc) with human erythrocytes is reported. Metoprolol is well known and acts mainly as a selective beta-1-antagonist. While erythrocyte aggregation, suspension osmolality and pH-values were unchanged, red cell deformability was markedly improved. Investigation into the furosemide-sensitive fluxes resulted in an inhibition of sodium efflux and in a constant water content of human erythrocytes. These in vitro results suggest that metoprolol induced improvement of red cell deformability cannot be explained by shape changes of erythrocytes.

Blood Viscosity↗
PubMed1984

[Treatment results in malignant tumors of the vulva, a retrospective analysis of 119 cases].

Between 1960 and 1980 111 patients with malignomas of the vulva were treated. Among these 86 cases were admitted primarily with view of treatment. Within the period conception of therapy was changed drastically. Where as in former time treatment consists in excision of the tumour with following conventional X-ray therapy, since 1973 therapy of choice was radical vulvectomy with inguinal lymphonodectomy. Based on these facts a retrospective comparison of the survival rates in possible, particularly distribution of stages is likely the same in the two groups. The group treated since 1973 has essential better survival rates. This can be attributed to the conception of radical operative treatment preferred in literature predominantly. Mortality rate is below 5 per cent which will be favourable in the geriatric clientele. To make the results of treatment comparable internationally a postoperative classification should be proposed like in breast cancer. The question of the position of an additional postoperative irradiation is to be answered only with aid of a prospective multicenter study.

Adult↗
PubMed1983

Indices of cardiac function during treatment with betamimetic drugs (fenoterol and hexoprenaline).

The limiting factor in the treatment of preterm labor by betamimetics is the effect of these drugs on heart rate and cardiac action. In this paper we compare these effects produced by hexoprenaline and fenoterol, which are both beta-sympathomimetic drugs now in clinical use. As indices of cardiac action we measured the pre-ejection period (PEP), the left ventricular ejection time (LVET) and their sum, namely total electromechanical systole (QS2) by thoracic impedance cardiography. In 20 individual tests, seven subjects were given both hexoprenaline and fenoterol on separate occasions in a dose relationship of 1 : 12.5. We found a relation between PEP/LVET on the one hand and the Heather-index (an impedance specific parameter of response to stress) on the other. Both parameters represent inotropic effects in cardiac action. With increasing betamimetic stimulation there was a decrease of PEP/LVET (-23% for hexoprenaline and -29% for fenoterol) and an increase in the Heather-index (+98% for hexoprenaline and +117% for fenoterol). These results are not statistically significantly different and so we cannot agree with Lipshitz [19 ]who reported less beta 1-stimulation with hexoprenaline.

Adult↗
PubMed1983

[Single-dose mezlocillin prophylaxis and postoperative morbidity after vaginal hysterectomy: pharmacokinetic and clinical results].

In this prospective, randomized study we evaluated the prophylactic administration of 5 g Meclocillin in a single dose. 100 patients undergoing vaginal hysterectomies were observed. Clinical parameters as well as Meclocillin concentrations in serum and myometrium were compared. We found a sufficient Meclocillin concentration in serum and myometrium 30 minutes after intravenous administration. In the control group (n = 50) 8 patients had a febrile postoperative course whereas there was 1 patient only in the treated group. A more detailed analysis regarding predisposing risk factors, urinary tract infections and pathogens of the vaginal wound secretions is presented. The single dose administration had no significant effect on the incidence of postoperative urinary tract infections. The preliminary result of our study reveals the single dose treatment to be a remarkable alternative to the three-dose-perioperative regimen. Regarding the general question of prophylactic antibiotic treatment at time of vaginal hysterectomy especially individual factors as well as preoperative risk factors have to be taken into account.

Drug Administration Schedule↗
PubMed1983

[Hypervolemic hemodilution in pre-eclampsia].

Studying 30 pregnant women, 26 resulted in a pre-eclampsia and 4 in a fetal intrauterine growth retardation. The patients were treated with 500 ml low molecular dextran per hour. We found a hemodilution, an increase of plasma viscosity (5.4%), and a raised cardiac output (32.4%). Resulting from the increased cardiac output we saw a raised systemic oxygen transport capacity in contrast to the hemodilution. The hemodilution is characterized by the increase in stroke volume, whereas heart rate and mean arterial blood pressure are remaining unchanged. The erythrocyte aggregation fell (32.4%) and colloid osmotic pressure raised (27%). Watching the clinical course, we observed a prolongation of gestation above 14 days in ten patients with pre-eclampsia and intrauterine growth retardation. One intrauterine death had to be noticed. The data suggest that only an early infusion therapy with low molecular colloids can be successful in the treatment of hemorheological disorders in pre-eclampsia.

Adult↗
PubMed1981

Hemoconcentration and pre-eclampsia.

We measured erythrocyte aggregation and hematocrit in 155 uncomplicated pregnancies and in 55 pregnant women with pre-eclampsia. In the later group we found increased erythrocyte aggregation and a higher hematocrit than in normal patients of comparable gestational age. Erythrocyte aggregation correlated well with plasma fibrinogen levels (r = 0.74) but other high molecular weight proteins such as alpha-2-macroglobulin, IgM and lipoproteins were not measured. Hematocrit showed correlation with mean arterial blood pressure (r = 0.69) and peripheral vascular resistance (r = 0.73). The possible effects of changes in hematocrit and erythrocyte aggregation on blood flow through the intervillous circulation are discussed as are the clinical implications of our findings.

Adult↗