Faculty Bibliography

We describe the clinical course of an 81-year-old woman who was evaluated for worsening symptomatology of spinal cord claudication. Diagnostic studies revealed mild lumbar canal stenosis at L3-4, severe stenosis at L4-5 with a myelogram-CT scan demonstrating a complete block at this level mainly a result of a hypertrophied ligamentum flavum. At surgery, the ligamentum was found to be thickened and to be causing severe compression of the dural tube. Pathologic studies of the excised ligamentum flavum revealed extensive amyloid protein deposition. The amyloid was not further classified with further medical evaluation and followup failing to identify any conditions associated with local or systemic amyloidosis.

Fifty-nine patients with acute gouty arthritis entered into a 7-day multicenter, double blind trial of ketoprofen versus indomethacin. Patients were randomly assigned to receive 100 mg of ketoprofen (n = 29 patients) or 50 mg of indomethacin (n = 30 patients) 3 times a day. More than 90% of the patients in each group reported pain relief within the 1st day of treatment. By Day 5, 7 patients in the ketoprofen group and 6 in the indomethacin group discontinued treatment because of complete or substantial pain relief. At the end of the study, most patients in both groups were rated as having marked improvement both by the investigators and by self-assessment. Three patients in each group withdrew prematurely because of drug related gastrointestinal disorders. Ketoprofen compared favorably for efficacy and safety with indomethacin in the treatment of gouty arthritis.

Codeine, a relatively weak oral narcotic agent, is the most frequently prescribed oral opiate drug. It is also frequently utilized as a control drug in comparative analgesic efficacy studies. These studies are often single dose analysis of pain relief following surgery or childbirth. We conducted a single dose, post-operative analysis of 116 patients who were randomly assigned to receive codeine 60 mg, acetaminophen 600 mg, the combination of codeine and acetaminophen at these doses, or a placebo. Only the combination agent was uniformly superior to placebo. Codeine 60 mg was not consistently superior to placebo in this post-operative single dose analysis. A review of the literature confirms the difficulty in unequivocally establishing the value of codeine as an analgesic, in acceptable oral doses, in the single dose setting. Previous reports, however, suggest that the multiple doses of codeine may afford adequate analgesia. Interpretation of single dose studies with extrapolation to repeated dosing in the practice setting is difficult.

In this long-term, double-blind, multicenter study, efficacy and safety of zomepirac sodium were compared with those of aspirin for treatment of the chronic pain associated with osteoarthritis in 607 patients, 405 of whom received zomepirac and 202 of whom received aspirin. Final evaluations during one year of treatment showed zomepirac significantly more effective than aspirin for reducing pain at rest (P = 0.02) and average pain (P = 0.04). Moreover, zomepirac was rated better than aspirin in physician global evaluations of overall response to therapy (P = 0.02) and patient evaluations of pain relief (P = 0.03). At the end of the one-year study, patients were permitted to extend double-blind treatment for an additional year. In final evaluations for patients who continued, zomepirac was significantly better than aspirin for relief of pain on motion (P = 0.05) and also in patient global evaluations of therapeutic response (P = 0.02). Side effect profiles during the first year of therapy were generally comparable for zomepirac and aspirin. However, complaints related to the special senses, especially tinnitus and hearing disturbances, were reported more frequently during aspirin therapy, and urogenital side effects were more common during zomepirac therapy. For both drug groups, the overall incidence of side effects was lower in the second year than in the first. This is the first published study to show a nonsteroidal antiinflammatory agent to be more effective than aspirin for the long-term treatment of pain associated with osteoarthritis.

Zomepirac sodium, a new, nonnarcotic analgesic agent, was compared with the combination of propoxyphene/acetaminophen in a placebo-controlled, double-blind, single-dose study in 196 hospitalized postsurgical patients with pain severe enough to require a prescription analgesic. Patients received 100 mg zomepirac sodium, 50 mg zomepirac sodium, 100 mg propoxyphene napsylate with 650 mg acetaminophen, or placebo. Total pain relief during the 6-hour observation period showed that 100 mg zomepirac sodium was significantly more effective than the propoxyphene combination. All active drugs were superior to placebo. Percentages of patients requiring remedication before the end of the study were: 77 per cent for placebo, 48 per cent for propoxyphene/acetaminophen, 43 per cent for 50 mg zomepirac sodium, and 29 per cent for 100 mg zomepirac sodium. The numbers of patients reporting side effects were not significantly different among the treatment groups. These results confirm those of other single-dose pain studies which showed 100 mg zomepirac sodium significantly more efficacious than the propoxyphene/acetaminophen combination.

The diagnosis of gout and pseudogout has traditionally been established by the identification, in synovial fluid, of monosodium urate and calcium pyrophosphate dihydrate crystals with compensated polarizing light microscopy. In this paper the utility of electron microscopy in establishing these diagnosis in two cases, when the conventional means of synovial fluid analysis had failed to do so, is discussed. The application of ultrastructural analysis of synovial fluid increases diagnostic capability in the crystal deposition diseases, and it is recommended for those patients in whom the more usual studies have not established a diagnosis