Etienne LeBel

Synthesis, tissue distribution and tumor uptake of 99mTc- and 67Ga-tetrasulfophthalocyanine.

Complexes of tetrasulfophthalocyanine with 99mTc, 69Ga and 67Ga were prepared by the condensation of sulfophthalic acid with the appropriate metal-species. The Ga-complex was also obtained by exchange of the central hydrogens of the empty tetrasulfophthalocyanine. The labeled complexes were purified by thin layer chromatography and characterized by their chromatographic properties. Their biodistribution in rabbits and tumor-bearing rats revealed that most of the radioactivity accumulated in the kidneys, liver, ovaries, adrenals and spleen. Comparison of these distribution pattern with those of [99mTc]pertechnetate and 67Ga-citrate confirmed the in vivo stability of the labeled complexes. The 67Ga-complex reached better tumor-to-blood and tumor-to-muscle ratios than 67Ga-citrate.

The Influence of Vesical Distension on the Urethral Resistance to Flow: A Possible Role for Prostaglandins?

The possible role of prostaglandins in the mediation and/or modulation of the urethral response to vesical distension was investigated in female dogs. Three criteria for the possible involvement of these mediators have been investigated. Indomethacin could block the reduction of urethral resistance observed during vesical distension. Intra-arterial infusion of exogenous prostaglandin E2 resulted in a dose-dependent reduction in the urethral resistance to flow. Moreover, a significant release of prostaglandin E2 in the venous blood during the course of vesical distension could be demonstrated. The functional significance, mechanisms of release and mode of action of these highly active lipids are discussed.

Comparative Gastrointestinal Blood Loss Associated with Placebo, Aspirin, and Nabumetone as Assessed by Radiochromium (51Cr)

Nabumetone differs from most other nonsteroidal anti‐inflammatory drugs. It is presented to the gut as a nonacidic prodrug, and is metabolized to its active form after absorption. Studies in animals and humans suggest it is less irritating to the gastrointestinal mucosa. This study compared the gastrointestinal microbleeding induced by nabumetone to aspirin (acetylsalicylic acid, ASA), and placebo in a double blind parallel study using chromium 51Cr labelled red cells to quantitate fecal blood loss (FBL) in healthy volunteers. Thirty subjects were randomized to treatment with nabumetone (2000 mg), ASA (3.6 g) or placebo for 21 days following a 7 day placebo period. Six subjects served as untreated controls. FBL in nabumetone treated subjects was not significantly different to placebo or untreated subjects. In contrast, ASA‐treated subjects exhibited significantly increased FBL than the other 3 groups (P < .0001).

Gastrointestinal Blood Loss of Oxaprozin and Aspirin with Placebo Control

Abstract: The objective of this study was to compare the effects of oxaprozin (4,5‐diphenyl‐2‐oxazolepropionic acid), a nonsteroidal, antiinflammatory compound, and aspirin in a double‐blind, placebo‐controlled study to estimate gastrointestinal bleeding. The determination of fecal blood loss was made quantitatively by the use of the radioactive (51Cr) technique. During the first week, subjects were controlled with and without placebo. At the end of the second week, the subjects were divided and randomly assigned to one of three groups; 10 received 1200 mg oxaprozin (600 mg twice daily), 11 received 3900 mg aspirin (975 mg four times a day), and the remaining 8 subjects received placebo for two weeks. During the last two weeks, all received placebo again. A statistical analysis of variance showed that there were no statistical differences between the groups during the first and last two weeks of placebo therapy. During the active treatment period, weeks 3 and 4, there were statistically significant differences among the three groups. The mean blood loss during week 3 was significantly greater for the aspirin group, 8.8 ml/day, than the oxaprozin group, 3.3 ml/day (P < 0.05), and the placebo group, 1.4 ml/day (P < 0.001). The smaller difference between oxaprozin and placebo was also significant (P < 0.05). During the fourth week, the mean daily blood loss among oxaprozin patients had decreased to 2.3 ml/day, and no statistically significant difference from placebo (1.1 ml/day) was found.

The use of a 51Cr technique to detect gastrointestinal microbleeding associated with nonsteroidal antiinflammatory drugs

Of techniques used to evaluate gastrointestinal (GI) bleeding, use of radiochromium (51Cr)-tagged erythrocytes is the most quantitative and scientifically acceptable method. The value of this technique as well as systematic errors possible with its use are discussed. The medical literature concerning 51Cr evaluation of GI microbleeding with naproxen therapy is critically reviewed. We suggest that future studies using this technique be parallel, randomized, double-blind, and include a 1-week placebo baseline phase for all subjects. Treatment with nonsteroidal antiinflammatory drugs (NSAIDs) should last 3 to 4 weeks. A parallel group of subjects should receive placebo throughout the study. For valid statistical analyses, randomization must achieve baseline comparability of weight, height, age, and sex in the treatment groups. Data transformations may be necessary to satisfy the assumptions of the statistical model. Following these guidelines will enable investigators to better evaluate GI microbleeding during treatment with naproxen or other NSAIDs, and, hopefully, to establish the safety profiles of these drugs.

Comparative study of gastrointestinal microbleeding caused by aspirin, fenbufen, and placebo☆

Fifty volunteers, randomly divided into five groups, received placebo, fenbufen, or aspirin at dosages used in treating osteoarthritis and rheumatoid arthritis (fenbufen, 600 or 900 mg daily; aspirin, 3.6 g daily) for 28 days. Following radioactive chromium labeling of red cells in each subject, stool specimens were collected weekly for determination of blood loss by radioisotope procedure. Statistical analyses demonstrated no significant differences in gastrointestinal microbleeding between subjects who received fenbufen (600 or 900 mg daily) and those who received placebo. Conversely, there were significant (p less than 0.01) differences in microbleeding between subjects given aspirin and those given either dosage of fenbufen or placebo.