The adverse effects of PGE2 on aortic smooth muscle cell viability and cytokine secretion in vitro and the apparent effect of anti-inflammatory drugs to lower aneurysm growth rates suggest that selective inhibition of PGE2 synthesis could be an effective treatment to curtail aneurysm expansion.

short-term explants of AAA are a novel method to assess the effects of drugs on aneurysm tissue. Indomethacin reduces the production of PGE2, IL-1beta and IL-6, suggesting that cyclo-oxygenase-2 inhibitors may control the inflammation in the aneurysm wall and potentially limit AAA growth.

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BACKGROUND: Prostaglandin E2 (PGE2) and inflammatory cytokine levels are raised in the wall of abdominal aortic aneurysms (AAAs) and inflammatory processes appear to contribute to aneurysm expansion. The effect of PGE2 on aortic smooth muscle cells (SMCs) and the influence of indomethacin on AAA growth and production of inflammatory mediators were investigated. METHODS: Proliferation and apoptosis of aortic SMCs cultured with PGE2 were assessed by 5-bromo-2'-deoxyuridine uptake and oligonucleosome enzyme-linked immunosorbent assay. Full-thickness AAA explant cultures were used to measure the secretion of PGE2, interleukin (IL) 1beta and IL-6 in the presence and absence of indomethacin. In a case-control study, the effect of non-steroidal anti-inflammatory drugs (NSAIDs), including indomethacin, on AAA growth was examined. RESULTS: PGE2 suppressed proliferation (IC50 6 ng ml-1) and increased apoptosis of aneurysm SMCs. Indomethacin diminished secretion of PGE2, IL-1beta and IL-6 by AAA explants (see Table below). The median AAA growth rate of 19 patients taking NSAIDs was 1.8 (range 0-11.2) mm per year compared with 3.2 (0.4-10.9) mm per year in 59 patients (matched for age, sex, smoking and initial AAA diameter) not taking these drugs (P = 0.004). CONCLUSION: PGE2 is produced in the AAA wall in concentrations that are detrimental to SMCs. Indomethacin reduces PGE2, IL-1beta and IL-6 synthesis in aneurysm tissue and NSAIDs appear to reduce AAA growth. These drugs warrant further consideration for the treatment of AAA.

SummaryFour patients are described who had a significant elevation of serum thyroxine-binding globulin (TBG). Review of these patients indicated that inappropriate therapy for thyrotoxicosis had been given in three cases. A study of our laboratory records revealed that significant TBG elevation was a relatively common phenomenon which occurred in approximately 0 45% of our hospital population. Patients with this abnormality have serum thyroxine levels which are comparable to those with clinical thyrotoxicosis. Tri-iodothyronine is frequently elevated though less so than in patients with clinical thyrotoxicosis. Measurement of TBG is indicated in all cases of hyperthyroxinaemia in which the clinical features of thyrotoxicosis are doubtful. The TRH test was found to be most useful in evaluating the thyroid status of these patients.