Response of oral leukoplakia to beta-carotene.

Leukoplakia is associated with increased risk of oral cancer and is considered a premalignant lesion. Retinoids, particularly 13-cis retinoic acid, can frequently reverse leukoplakia. However, these drugs have considerable toxicity and are not suitable for large-scale use in the prevention of oral cancer. Beta-carotene is a naturally occurring, nontoxic carotenoid with biologic properties that suggest that it might be efficacious against oral leukoplakia. In 1986, we began a randomized study of 13-cis retinoic acid (1 mg/kg/d) versus beta-carotene (30 mg/d) in leukoplakia. However, owing to the marked differences in toxicity between the two compounds outlined in the consent form, 11 of the initial 16 eligible patients refused to participate unless they were "guaranteed" beta-carotene. Therefore, the study design was changed to a phase II trial of beta-carotene in which the compound was given daily for 3 months. Responding patients were continued for another 3 months of treatment. All lesions were examined histologically at entry. Responses were monitored by bidimensional measurements and photography done at entry, then monthly while on treatment and at study completion. Twenty-four evaluable patients were treated, and 17 had major responses (two complete, 15 partial), a response rate of 71% (95% confidence limits, 53% to 89%). There was no significant toxicity requiring drug discontinuation or dose reduction. These results indicate that beta-carotene has substantial activity in oral premalignancy. Because of its lack of toxicity, it is an excellent candidate for a preventive agent for oral cancer.

A double-blind, randomized study of naproxen sodium, ibuprofen, and placebo in postoperative dental pain.

In a double-blind, parallel, placebo-controlled study, 203 patients with post-operative dental pain following the extraction of one or two bony impacted third molars were randomized to receive a single dose of naproxen sodium 220 mg, ibuprofen 200 mg or placebo. Pain intensity and pain relief were assessed at intervals for 12 hours postdose. Both active drugs demonstrated superior analgesic efficacy over placebo. Naproxen sodium and ibuprofen were comparable both in onset of analgesic action and in pain relief. From 1 to 12 hours postdose, naproxen sodium showed a trend for superior analgesic efficacy compared with ibuprofen; this trend reached statistical significance at the 12-hour time point. Both drugs were well-tolerated and effective analgesics for postoperative dental pain.

A single-dose, double-blind comparison of naproxen sodium, acetaminophen, and placebo in postoperative dental pain.

The analgesic efficacy and duration of action of naproxen sodium 440 mg (n = 92), acetaminophen 1000 mg (n = 89), and placebo (n = 45) were compared in a single-dose, randomized, double-blind, 12-hour study of patients with at least moderate pain secondary to extraction of three or four third molars. Time to remedication, a measure of duration of analgesic effect, was significantly longer (P < 0.001) with naproxen sodium (median, 9.9 hours) than with either acetaminophen (median, 3.1 hours) or placebo (median, 2.0 hours). Naproxen sodium was also superior to acetaminophen for peak pain intensity difference (visual analog scale), summed pain intensity differences, total pain relief, peak pain relief, time to reduction of pain by 50%, and overall rating. The overall percentages of patients reporting adverse events, and the types of events reported, were comparable with the three treatments. Thus naproxen sodium demonstrated superior efficacy and similar tolerability to acetaminophen in this postoperative dental pain model.

Treatment of sex offenders with Depo-Provera.

Medroxyprogesterone acetate (MPA) is capable of reducing male testosterone blood levels with a corresponding reduction in sexual interest and activity. An attempt to evaluate its effectiveness with court committed sexual offenders was made with eight subjects each serving as his own control by alternating Depo-Provera injections for 16 weeks with saline injections for a corresponding 16 weeks. This paper reports the results of this study and the conclusions that appear to be appropriate.