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Biomedical subjects

E Luedin

Publications and source records attributed to E Luedin.

3 recordsLinked to original sources

Increase of plasma nonesterified fatty acid concentration and decrease of albumin binding affinity after intravenous injection of glycocholate-lecithin mixed micelles.

Lipophilic drugs intended for intravenous use can be solubilized by mixed-micellar systems containing glycoholic acid and lecithin (MM). Our present studies determined the influence of such MM preparations on albumin binding of monoacetyldiaminodiphenyl sulfone (MADDS), a deputy ligand for bilirubin. After intravenous administration of MMs to healthy male and female adult volunteers, concentration-time profiles of bile acid and nonesterified (NEFA) and esterified fatty acids were obtained as well. In vitro experiments with blood from adults and from neonatal cords indicated a modest reduction in reserve albumin for binding of MADDS after addition of MMs, resulting from glycocholic acid in the micellar preparation. After injection of MM preparations with up to 530 mg glycocholic acid, a rapid decrease of the reserve albumin was observed. The effect was more pronounced in men than in women and resulted in different areas under the time curve for the decrease (p = 0.049). At their maximum (3 to 10 minutes after MM doses) the decreases averaged (+/- SD) 68% +/- 14% in men and 45% +/- 8.5% in women. Low reserve albumin concentrations were maintained over 20 minutes despite rapidly declining bile acid concentrations. Injection of MM caused a drastic increase of NEFA in the serum samples with a more pronounced effect in men (average +/- SD increase: 473% +/- 93%) than in women (148% +/- 91%) (p = 0.01). The changes in NEFA concentrations ran reciprocal to the changes of reserve albumin for binding MADDS. In all subjects the increase in NEFA was accompanied by a decrease in reserve albumin for palmitate. Fatty acid binding to albumin was well restored within 1 hour. Thus, before drugs incorporated in MM can be prescribed to neonates who are at risk for having kernicterus, the impact of intravenous MM on bilirubin binding and NEFA levels must be investigated in that patient population.

Adult

Time course of thrombolysis induced by intravenous bolus or infusion of tissue plasminogen activator in a rabbit jugular vein thrombosis model.

Tissue plasminogen activator is a thrombolytic agent that has been shown to be efficient in patients with myocardial infarction or pulmonary embolus. However, little is known about the time course and the dose dependency of its thrombolytic effect. The goal of our study was to investigate the time course of the thrombolysis induced by increasing doses of tissue plasminogen activator (t-PA) given either as a continuous infusion (0.0625-1 mg/kg) or as a bolus (0.05-0.4 mg/kg). For this purpose, we modified a previously described rabbit jugular vein thrombosis model by using an external gamma counter to follow continuously the thrombolysis. After administration of t-PA as either an infusion or a bolus, the rate and the extent of thrombolysis were dose dependent. The thrombus size decreased regularly following an exponential curve and reached a lower asymptote implicating an unlysable thrombus. As expected, after bolus injection, t-PA was rapidly inhibited resulting in a duration of action of approximately 15 minutes; this was independent of the dose. Surprisingly, during continuous infusion of t-PA for as long as 4 hours, the duration of action was limited to about 2 hours, although the plasma t-PA activity levels remained stable. Although the rate of inhibition was lower and thus the duration of action was longer during continuous infusion of t-PA than after a bolus injection, the extent of thrombolysis was similar when the same dose of t-PA was given as either a bolus or an infusion. These findings could be attributed to the higher initial rate of thrombolysis observed after a bolus injection.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Comparison of a CEA-EIA assay based on monoclonal antibody with a CEA-RIA assay with polyclonal antiserum.

A monoclonal CEA-EIA assay is evaluated with respect to clinically pertinent data. Comparison is done with the conventional CEA-RIA assay (Roche). Good interlaboratory reproducibility was found, and the stability was very good over the one year evaluation period. The EIA assay could be performed in samples of serum and plasma with compatible results. The correlation between the EIA and RIA values was different in different diagnostic groups, with high correlation in colo-rectal cancer, and low in non-malignant diseases, in which the EIA assay had a lower frequency of CEA positive values. In colo-rectal cancer the RIA assay shows a 20% specificity improvement compared with the EIA assay. This was also reflected in better predictability for true positive and true negative cancer diagnosis in this group of patients as well as increased ability to discriminate between malignant and non-malignant diseases. In other groups of patients, like lung cancer and uterine cervical cancer, such improvement was not seen. The discrimination between malignant and non-malignant diseases was comparable to that of the RIA assay. In follow-up series the EIA and RIA assays detected recurrences and responses to treatment in a quite similar way. In most cases of recurrences from colo-rectal cancer, however, the EIA values increased faster and were a better indicator for recurrent disease than the RIA values.

Antibodies, Monoclonal