Monitoring activity of fibrinolytic agents. A therapeutic challenge.

The recognition that thrombolytic therapy may be beneficial for coronary thrombolysis has led to an increased use of plasminogen activators in critically ill patients, sometimes with inadequate monitoring. This review delineates the components of the fibrinolytic system, describes mechanisms of fibrinolysis, and presents practical guidelines for monitoring the use of activators of the system.

16 alpha-[77Br]bromoestradiol: dosimetry and preliminary clinical studies.

An estrogen-receptor-binding radiopharmaceutical, 16 alpha-[77Br]bromoestradiol-17 beta, has been used successfully at high specific activity to image carcinogen-induced mammary tumors in rats and in preliminary studies to image breast tumors in patients. The biodistribution of the labeled estrogen in rats and its clearance in a monkey were used to estimate the radiation absorbed doses to a human resulting from administration of the radiopharmaceutical. Preliminary imaging studies in patients with mammary carcinoma show promising results and warrant further development of radiolabeled estrogens, particularly those carrying positron emitters that could permit positron emission tomography--for example Br-75 or F-18.

Prospects for in vivo Raman spectroscopy.

Raman spectroscopy is a potentially important clinical tool for real-time diagnosis of disease and in situ evaluation of living tissue. The purpose of this article is to review the biological and physical basis of Raman spectroscopy of tissue, to assess the current status of the field and to explore future directions. The principles of Raman spectroscopy and the molecular level information it provides are explained. An overview of the evolution of Raman spectroscopic techniques in biology and medicine, from early investigations using visible laser excitation to present-day technology based on near-infrared laser excitation and charge-coupled device array detection, is presented. State-of-the-art Raman spectrometer systems for research laboratory and clinical settings are described. Modern methods of multivariate spectral analysis for extracting diagnostic, chemical and morphological information are reviewed. Several in-depth applications are presented to illustrate the methods of collecting, processing and analysing data, as well as the range of medical applications under study. Finally, the issues to be addressed in implementing Raman spectroscopy in various clinical applications, as well as some long-term directions for future study, are discussed.

Extensive cross-reactive idiotypy among guinea-pig anti-TMA antibodies.

The extensive cross-reactivity of the immune response by strain 13 (S-13) and outbred guinea-pigs (GP) to either the bivalent antigen L-tyrosine-p-azophenyltrimethylammonium (tyr(TMA)) [H-L-tyr(TMA)-NH-(CH2)3]2 (T-S-T) or the conjugate 3-(p-trimethylphenylazo)-N-acetyl-L-tyrosylglycylglycine-bovine serum albumin (T-S-B) was examined. Antibody (Ab) isolated from a single T-S-B immune S-13 animal by affinity chromatography (proband) was used to induce anti-sera (anti-Id) in a rabbit and a syngeneic S-13 GP. These anti-Ids were both shown to be idiotype specific by means of a tube binding radioimmunoassay (TBRIA). A series of S-13 anti-(T-S-B), S-13 anti-(T-S-T), and outbred anti-(T-S-B) antisera were tested as inhibitors in the TBRIA through a range of 6-200 ng of anti-TMA Ab equivalent. Each was found to inhibit extensively, indicating a considerable amount of cross-reactivity of idiotypes present in the sera. In general, the rabbit anti-Id recognized more cross-reactivity among the various antisera than did the GP reagent, particularly among those from T-S-B immune S-13 animals. Addition of free "hapten" tyr(TMA) as an inhibitor specifically displaced 55% of the label from the rabbit reagent at 10(-5)M, while only 25% of binding of the proband to GP anti-Id was inhibitable at this concentration. These findings suggest that the rabbit and GP anti-Ids are directed predominantly to different determinants, the rabbit recognizing the less variant, hapten-binding portion of the GP Ab more than does the syngeneic GP reagent. Data from isoelectric focus patterns support the impression of a highly restricted Ab response to TMA. While each serum gives a distinct binding pattern, several bands appear shared by all responders.