[Safety and efficacy of LK565--a new polymer ultrasound contrast medium]. / Untersuchungen zur Sicherheit und Effizienz von LK565--einem neuen Polymer-Ultraschallkontrastmittel.

We tested a newly developed ultrasound contrast agent (LK565) from poly-aspartic acid (PAA; particle size 3 microns; particle content: air) in 15 healthy male probands (20-38 years) in doses of 10, 30 and 100 mg intravenously. One day and immediately before the study a routine laboratory test, an ECG and an EEG were performed. The EEG was continued through the complete time period that the ultrasound contrast lasted, i.e., up to one hour after the injection. All probands were followed clinically for 24 hours when the routine laboratory and the ECG were repeated. All subjects tolerated the contrast agent well. There were no changes in either the EEG or in the ECGs performed throughout the study. There were no significant laboratory changes except for a small and transient increase in the neutrophil count in five probands receiving the highest dose. All injections with 10 mg led to a significant improvement in the color Doppler signal. All injections with 30 and 100 mg led to a very strong echo contrast lasting for 5 to 12 minutes in the harmonic B-mode. Using the latter, fragments of intramyocardial coronaries could be visualized. The tested ultrasound polymer contrast agent was safe, well tolerated and efficient in this acute study.

Quantitative analysis of HBY 097 and its metabolites in human serum and urine by HPLC.

Two HPLC methods were developed: one for the quantitation of HBY 097 reverse transcriptase inhibitor and its metabolites M2 and M3 in human serum, and one for the quantitation of metabolite M5 in urine. The HPLC procedure for the quantitation of HBY 097 and its metabolites M2 and M3 in human serum involved protein precipitation with acetonitrile followed by automated on-line trace enrichment. The HPLC procedure for the analysis of metabolite M5 in urine involved enzymatic hydrolysis of urine with beta-glucuronidase to convert metabolite M5 (glucuronide of M3) to M3. Reverse phase chromatographic separation with gradient elution. UV detection at 335 nm, and internal standard were used to quantitate analytes in both procedures. The lower quantitation limits were 25 ng ml-1 for HBY 097 and metabolites M2 and M3 in serum, and 0.5 microgram ml-1 for the metabolite M5 in urine measured as metabolite M3 after hydrolysis. The HBY 097 and metabolite M3 concentrations were specific but metabolite M2 was semi-specific because the two diastereomers of M2 were not resolved by the present chromatographic procedure. Both procedures were applied to the quantitation of HBY 097 and its metabolites in serum and urine of HIV positive patients who were enrolled in a clinical study of drug safety and pharmacokinetics.

[Polymer microparticles for right and left heart echocardiography and imaging myocardial perfusion after peripheral vein injection]. / Polymer-Mikropartikel für Rechts-und Linksherzechokardiographie und Darstellung der Myokardperfusion nach periphervenöser Injektion.

It is conceivable that a stable ultrasound contrast agent could be used for reproducible right and left heart echocardiography and myocardial visualization after intravenous injection. Microparticles from different polymers and preparation procedures were screened in six dogs leading to one superior agent with reproducible high quality echo contrast in doses of 1 mg/kg. This special agent is based on condensates of aspartic acid, ethanolamine and decanoic acid. Out of this material particles were formed with an average diameter of 2 micrometers. The easily suspendable particles were used for the following studies in a dose of 1 mg/kg intravenously in eight pigs. Maximal video intensity averaged 116 +/- 42 relative intensity units (IU) in the right, 137 +/- 42 IU in the left ventricle, 42 +/- 7 in the normally perfused and 11 +/- 2 in the hypoperfused myocardium after circumflex ligature. The area under the intensity curve was 1942 +/- 100 IUxs in the right, 2452 +/- 1291 IUxs in the left ventricle, 518 +/- 124 in the normally perfused and 202 +/- 94 in the hypoperfused myocardium after circumflex ligature. There was no change of heart rate, central arterial or pulmonary artery pressure during and after the injections. There was also no loss of echo intensity during the passage of contrast material through the heart due to systolic pressure. The described agent can be used for the opacification and ultrasonic visualization of the right and left heart as well as normally and hypoperfused myocardium without visible side-effects in animal studies.

Experimental high density optical memory using the dichroic absorption of the m(a) color center.

An experimental, high density optical memory using M(A) color centers in KCI has been built to study the application of color centers as read, write, and erase computer bulk memories. M(A) centers are employed as a binary indicator by making use of their ability to reorient in the KCI lattice when excited with either [110] or [110] polarized 531-nm light. Information is read out with circularly polarized 531-nm light. Results indicate that writing times of less than 5 microsec and packing densities exceeding 10(6) bits/cm(2) will be possible in a fully developed system.