Biomedical subjects

H Jaeger

Publications and source records attributed to H Jaeger.

At least 37 records · Page 2Linked to original sources

PubMed1992

Measurements of volume changes and venous pressure in the human lower leg during walking and running.

This study investigates whether walking or running prevents the formation of edema in the lower leg. In 18 volunteers changes in calf volume were measured using strain gauge plethysmography during slow (3 km/h) and fast (6 km/h) walking or running (10 km/h) on a treadmill for 20 min each. Venous pressure was measured in a superficial vein near the ankle. Low-pass filtering removed motion artifacts from the signals. Slow walking reduced the calf volume in a biphasic manner: a rapid decrease was followed by a slow decline, lasting from about minute 2 to minute 20, its mean rate being -0.073%/min. Besides a rapid initial decrease, no significant change was observed during fast walking. During running, the calf volume first increased within 7 min to a maximum of 2.5% and subsequently decreased with a mean rate of -0.096%/min. The medians of venous pressure were 84.0, 23.5, 30.4, and 29.5 mmHg during quiet standing, slow and fast walking, and running, respectively. The experimental results prove the hypothesis that walking prevents dependent edema formation. This effect, however, cannot be fully explained by the lowered venous pressures.

Adult↗

PubMed1992

Evaluation of bioavailability and pharmacokinetics of two isosorbide-5-mononitrate preparations in healthy volunteers.

The objective of this study was to determine both the pharmacokinetic parameters and the bioavailability of two commercial 20-mg isosorbide-5-mononitrate (IS-5-MN) preparations (test and reference preparation) after single oral administration. For this purpose, the test and the reference preparation were examined in 24 healthy male volunteers according to a randomized 2-way cross-over design, blood samples were withdrawn up to 24 hours postadministration, and plasma concentrations of IS-5-MN were quantified by a gas chromatography (GC) method. Both preparations led to peak plasma levels of approximately 360 ng/mL IS-5-MN in the mean 0.76 hour (test) and 0.94 hour (reference preparation) after application; the plasma half-lives were about 5.2 hours, and for the areas under the curve (AUC(0-infinity)), mean values of 2741 (test preparation) and 2742 hour.ng/mL (reference preparation) were found. The statistical comparison (analysis of variance, confidence intervals) of the pharmacokinetic parameters found in the study resulted in bioequivalence of both IS-5-MN preparations. The undesired side effects/concomitant symptoms observed are known to occur after IS-5-MN administration.

Administration, Oral↗

PubMed1992

In vitro lymphocyte functions in the presence of bovine surfactant and its phospholipid fractions.

Endotracheal administration of human or xenogenic surfactant preparations is an effective treatment of the respiratory distress syndrome of preterm infants. The application of large amounts of phospholipids to the lung may result in a significant alteration of the local immune response. We studied the influence of the bovine surfactant preparation SF-RI 1 (Alveofact) on lymphocyte functions in vitro. PHA-induced cell proliferation and immunoglobulin synthesis in the presence of whole surfactant as well as six different defined phospholipids were investigated. A marked concentration-dependent suppression of immunoglobulin production independent of the immunoglobulin isotype and cell proliferation was observed in the range of 5 ng/ml-3 mg/ml of a single phospholipid (or SF-RI 1 respectively). It could be demonstrated that suppression of lymphocyte functions was only due to the phospholipid content of the surfactant preparation. These data indicate that in vivo immune functions may be significantly altered by the administration of exogenous surfactant. This may be particularly important in the presence of primary or secondary pulmonary infections.

Chromatography, Thin Layer↗

PubMed1991

A prospective and randomised study comparing the incidence of infusion phlebitis during continuous and cyclic peripheral parenteral nutrition.

Phlebitis is a major obstacle to successful and prolonged peripheral parenteral nutrition (PPN). This study evaluated the effects of elective changes of the intravenous cannula and cyclic infusion of PPN on the incidence and the severity of phlebitis. 51 consecutive patients requiring PPN were randomised into three groups. Group 1 received PPN continuously through a line which was changed only on evidence of phlebitis. In Group 2 intravenous lines were changed every 24h. Group 3 patients received PPN as a 12-h infusion after which the intravenous cannula was withdrawn. All patients received 1800 non-protein calories and 9.4g nitrogen daily. Infusion sites were assessed daily for phlebitis and this was scored using a modified Maddox scale. The mean (range) duration of PPN was 7.5 (1-13), 10.0 (2-42) and 8.2 (3-14) days in the three groups respectively. Severe phlebitis occurred more frequently (p < 0.05) in Group 1 compared to Group 2 or Group 3. The overall incidence of phlebitis assessed from the mean value of the Maddox scores for each group was highest in Group 1 and was significantly greater than that observed in either Group 2 (p < 0.05) or Group 3 (p < 0.001). Group 3 patients who received cyclic PPN had the lowest incidence of phlebitis. The results of this study suggest that the incidence of infusion phlebitis is minimised during PPN by the cyclic infusion of nutrient solutions.

Journal Article↗

PubMed1991

Multiple peaks and low bioavailability of furosemide correlate with the volume of fluid ingested.

Two different single dose cross-over bioavailability studies were performed comparing a new oral furosemide preparation (test preparation = preparation A) with a marketed standard with a marketed standard preparation (reference preparation = preparation B). Test and reference preparation contained 40 mg of furosemide each. Into both studies, 18 healthy male volunteers were included; 4 volunteers participated in both studies. In study 1, the volunteers ingested the tested preparations together with 300 ml of an electrolyte solution in order to substitute volume and electrolyte deficits. Additional 200 ml were given 30 min post dose, 500 ml during the next 30 min and 1000 ml during the second hour after drug intake. In study 2, the tested preparations were ingested together with 200 ml of water without any additional volume substitution. The plasma concentration curves of study 1 showed a double peaking with a first maximum of furosemide levels at 1 h and a second peak at 3 h and 4 h, respectively, on average. The concentration-time curves of study 2 showed a single peak 1 h p.a. in the mean for both preparations. The relative bioavailability of preparation A was about 67% in study 1 compared to study 2. Preparation B showed a relative bioavailability of 59% in study 1 compared to study 2.

Adult↗

PubMed1991

[Plasma and urine kinetics of amitriptyline oxide and its metabolites. Comparison of intravenous infusion and oral administration in volunteers].

The study objective was to obtain detailed information on the plasma and urine kinetics of amitriptylinoxide (CAS 4317-14-0) and its metabolites. For this reason, 60 mg of amitriptylinoxide was administered to 12 subjects, both by intravenous infusion and by oral dosage, in a study performed according to a randomized two-way cross-over design. In plasma, we succeeded in analyzing the metabolites amitriptyline and nortriptyline in addition to the parent substance amitriptyloxide. The tests for the parent substance amitriptylinoxide revealed maximum plasma levels of 721 and 686 ng/ml at 1.96 h (i.v. infusion) and 0.82 h (oral formulation), respectively. Mean values of 2331 (infusion) and 1714 h.ng/ml (oral formulation) were determined for the area under the curve from time 0 to infinity AUC (0-infinity). We also produced a comprehensive evaluation of amitriptyline, however, this was not possible for the metabolite nortriptyline. In urine, we succeeded in a reliable quantification of 4 metabolites, namely cis-OH-amitriptylinoxide, trans-OH-amitriptylinoxide, amitriptyline and OH-nortriptyline, in addition to the parent substance amitriptylinoxide. In individual samples, nortriptyline, cis-OH-amitriptyline and trans-OH-amitriptyline were additionally identified. In the course of the study, there were no reports or observations of any adverse reactions in addition to the side effects known for amitriptylinoxide from literature. There were no clinically relevant differences in tolerability observed between these two preparations.

Administration, Oral↗

PubMed1990

Comparison of serum and urine neopterin concentrations in patients with HIV-1 infection.

Urine and serum neopterin concentrations are now widely used to monitor patients with HIV-1 infection. However, there are no published studies comparing the levels in urine and serum, and relating both to the patients' immune status. Urine and serum neopterin concentrations correlated closely in our study population of 37 HIV-1 seropositive patients (34 homosexuals, 3 drug addicts) and 10 HIV-1 seronegative homosexuals. Our data further show that urine and serum neopterin concentrations correlate almost identically with the clinical and immunological presentation of HIV-1 infected individuals, as expressed by the Walter Reed Staging classification. In addition, there was no difference between the correlation of neopterin concentrations in either serum or urine with the Quetelet indices. It will depend on the clinical situation whether blood or urine sampling is preferred. Collection and handling of urine samples from HIV infected patients is less risky to health care personnel in HIV settings.

Adult↗

PubMed1990

Review of methods and criteria for the evaluation of bioequivalence studies.

Guidelines for the performance and analysis of bioequivalence studies are not very specific. The advantages and disadvantages of the following methods and tests are discussed: analysis of variance by summation or by use of general linear models, nonparametric procedures, aposteriori probabilities and tests on the normality of residuals and on the variability of the results. Arguments for or against an analysis of data after logarithmic transformation versus analysis of untransformed data are presented. If the confidence intervals lie within certain limits, preparations may be considered equivalent. The criteria leading to those limits are discussed. It is recommended that concentration-dependent data of bioequivalence studies be evaluated by analysis of variance after logarithmic transformation, applying general linear models. Data that by theoretical reasons cannot be normally or log-normally distributed should be analysed by nonparametric methods. Otherwise these methods can only be recommended if a significant deviation from normality has been noted and only for two-way cross-over designs. For a geometric evaluation (after logarithmic transformation) the regions of acceptance should be symmetrical in the logarithm, e.g. (80%, 125%).

Analysis of Variance↗

PubMed1990

Serum trace element levels in HIV-infected subjects.

The absolute number of T4 cells and the serum concentrations of Ca, Cu, Fe, K, Mg, P, Se, and Zn were determined in 59 Walter-Reed staged, HIV-infected men, compared to healthy controls, serum levels of Ca, Cu, and Fe were significantly higher, those of P and Se significantly lower in the HIV-infected subjects. In the HIV-infected cases, but not in the controls, the concentrations of Se and Zn, of Ca with Cu and Fe, and of Fe with P, were directly correlated. In the controls, the correlation between the levels of K and Mg was direct, and inverse between those of Zn and P. Trace element levels did not significantly correlate with WR-stage. However, the absolute number of T4 cells was directly correlated with the serum Mg concentration.

Acquired Immunodeficiency Syndrome↗

PubMed1990

[Comparison of the effect and tolerability of two glibenclamide preparations with different release rates].

In a double-blind, randomized, multicenter, two-way crossover study, efficacy and tolerability of two glibenclamide (CAS 1028-21-8) preparations with different rates of release were compared during a 28 day long-term treatment period for each preparation. It involved 80 patients with diabetes mellitus type II difficult to stabilize orally, who had received preliminary glibenclamide treatment. The switching from one treatment to the other in particular was strictly controlled: day profiles on glucose and insulin were prepared on the last day of the long-term therapy period and again on the first two days of the next long-term therapy period. Halfway through each treatment period and on the last day of each therapy period, the glucose content of the 24 h urine was determined in order to assess diabetes stabilization. The quality of diabetes stabilization and tolerability being comparable for both treatments, there were no statistically significant differences determined for AUC, Cmin, Cmax, tmin and tmax in the insulin day profile and glucose day profile on switching from treatment A (Glibenclamid-ratiopharm) to B (reference preparation) nor from B to A. The tolerability of both preparations was very good.

Aged↗

PubMed1990

Development of a high performance liquid chromatography method for the simultaneous measurement of prednisone and prednisolone.

An improved high performance liquid chromatographic assay (HPLC) is presented for the quantitative determination of prednisone and its main metabolite prednisolone. This HPLC assay, employing a UV-detector and dexamethasone as an internal standard, provides a selective and sensitive determination of glucocorticoids in plasma. The advantage of this method is the possibility of simultaneously measuring exogenic and endogenic glucocorticoids. The lower limit of quantification is 5 ng/ml.

Chromatography, High Pressure Liquid↗

PubMed1989

Bioequivalence and pharmacodynamics of a modified glibenclamide formulation in healthy volunteers.

A glibenclamide preparation (Glycolande N) with a modified galenic formulation was compared with a marketed standard preparation for bioequivalence and hypoglycaemic action after single oral administration of 3.5 mg. Twelve healthy male volunteers participated in this open two-way cross-over study. The confidence intervals around the mean values of the standard preparation were all in the range of +/- 20%. No significant differences were found between both formulations for Cmax, Tmax, AUC1 and AUC3. The glucose profiles were virtually equal. Both preparations are regarded as bioequivalent and therapeutically equivalent.

Adult↗

PubMed1989

Quantitative determination of verapamil and metabolites in human serum by high-performance liquid chromatography and its application to biopharmaceutic investigations.

A specific and sensitive high-performance liquid chromatographic method for the quantitative analysis of verapamil and N-desmethylverapamil in human serum is described. The analytes were extracted from serum using diethylether under alkaline conditions, followed by back extraction into dilute hydrochlorid acid for chromatographic analysis on a reversed-phase column with a mobile phase consisting of acetonitrile, water and perchloric acid at a flow rate of 1 l/min. The analytes were detected by fluorescence detection, the influence of temperature on retention is discussed. The method is linear, quantitative and reproducible for two calibration ranges in serum (2.5 ng/ml-100 ng/ml and 12.5 ng/ml-500 ng/ml) using peak area ratios analyte/internal standard for quantification. At ultimate sensitivity, concentrations down to 250 pg/ml could be assayed. The method was selective to 6 other metabolites of verapamil and common exogenous interferences. It was applicated to the serum samples of a comparative 120 mg - verapamil hydrochloride tablet single dose two-way cross-over study comprising 18 volunteers. The pharmacokinetic data for both formulations are presented.

Biopharmaceutics↗

PubMed1989

Performance of a slow-release formulation of isosorbide-5-mononitrate (ISMO retard).

From the in vitro release-rate constant of a new sustained-release (SR) preparation of 40 mg isosorbide-5-mononitrate, the concentration-time profile in healthy subjects could be excellently predicted. Therapeutically, effective concentrations of 100 ng/ml were achieved within 20 min and lasted up to a maximum of 15.6 h. The decline of concentrations below this value thereafter, guarantees the absence of tolerance development in chronic therapy. In a three-period change-over study, two other commercial SR preparations exhibited only 79% and 53% of the bioavailability of the new formulation, which was significant in both cases. Compared with literature data, the absolute bioavailability of the new form should lie in the order of at least 85%.

Adolescent↗

PubMed1989

[Bioavailability and pharmacokinetics of a new nifedipine preparation in healthy volunteers].

In the course of this trial the bioavailability and the essential pharmacokinetic parameters of a newly developed 10 mg nifedipine preparation were to be determined in comparison to a marketed reference preparation after single oral administration. For this purpose, the test and the reference preparation were examined in 16 healthy volunteers according to a randomized 2-way cross-over design (latin square), blood samples were withdrawn up to 16 h p.a. and plasma concentrations of nifedipine and NPO (primary metabolite of nifedipine) were quantified by a HPLC method. Both preparations led to mean maximum concentrations of nifedipine in plasma of 110 mg/ml about 0.5 h p.a.; the mean termial half-lives were 1.8 h (test preparation) and 1.7 h (reference preparation). The data found for the metabolite NPO largely corresponded to those of the parent substance, thus equal metabolisation and adequate pharmaceutical quality of the two galenics may be presumed. Statistical comparison (ANOVA, Pratt-Wilcoxon test) did not reveal any significant differences between the test and reference preparation and, apart from a minor deviation, confidence intervals according to Westlake were sufficiently small, such that the two formulations may be considered bioequivalent. No differences of clinical relevance were detected between the two preparations in assay. The undesired side effects/concomitant symptoms known after nifedipine administration were observed.

Adult↗

PubMed1988

Sensitive quantification of pseudoephedrine in human plasma and urine by high-performance liquid chromatography.

An assay for the selective quantification of pseudoephedrine in human plasma and urine was developed using high-performance liquid chromatography with UV detection at 205 nm. Analyte and internal standard were extracted from alkaline plasma or urine into a mixture of n-hexane and diethyl ether, and the organic phase was back-extracted into dilute acid. The chromatographic system comprises microparticulate cyanopropyl-silica as stationary phase and a ternary solvent mixture with ion-pair reagents as mobile phase. Using 0.25 ml plasma, the lower limit of quantification was 25 ng/ml with excellent linearity up to 1000 ng/ml. In urine, the calibration ranged from 2.5 to 100 micrograms/ml. The selectivity of the method was demonstrated for several pharmaceuticals with similar structures. The validated method was applied to a pharmacokinetic study with a single oral dose of 100 mg of pseudoephedrine in two galenic formulations. Precision and accuracy data of the assay and calculated pharmacokinetic parameters are presented.

Adolescent↗

PubMed1988

Tryptophan degradation in patients infected by human immunodeficiency virus.

Tryptophan and kynurenine were measured retrospectively in sera of 11 male patients with advanced human immunodeficiency virus (HIV) infection (Walter Reed stages 4 and 6). Tryptophan levels are significantly reduced to less than 50% in patients with HIV infection and kynurenine levels significantly elevated when compared to sex and age matched controls. The decrease of tryptophan levels might contribute to neurologic symptoms often associated with HIV infection. Since interferon-gamma induces degradation of tryptophan via the kynurenine pathway, the present results may be consistent with enhanced endogenous production of interferon-gamma in advanced HIV infection.

Acquired Immunodeficiency Syndrome↗

PubMed1988

Improved high-performance liquid chromatographic method for the determination of tiotixene in human serum.

The problem of accurate determination of tiotixene in body fluids is still challenging. Several methods have been published but most of them require a tedious, time-consuming sample preparation, are not specific enough and lack the necessary sensitivity or require highly sophisticated analytical devices. As carefully validated analytical methods represent the basis of conclusive clinical trials (e.g. evaluating bioavailability/bioequivalence), an assay was developed to fulfill these needs. The method present employs an HPLC system combined with a UV-detector and uses perazine as an internal standard. The achieved lower limit of detection in serum was 0.05 ng/ml and the calibration curves were linear in the range of 0.5-20 and 0.1-2.0 ng/ml, respectively. The chromatographic peaks were well resolved and the cis-/transisomers well separated. The imprecision and inaccuracy data typically ranged from 2 to 7%; the recovery from serum was always better than 80%. The assay has been successfully used for the determination of very low tiotixene serum levels during several clinical studies.

Calibration↗