A circadian signal of change of season in patients with seasonal affective disorder.

BACKGROUND: In animals, the circadian pacemaker regulates seasonal changes in behavior by transmitting a signal of day length to other sites in the organism. The signal is expressed reciprocally in the duration of nocturnal melatonin secretion, which is longer in winter than in summer. We investigated whether such a signal could mediate the effects of change of season on patients with seasonal affective disorder. METHODS: The duration of melatonin secretion in constant dim light was measured in winter and in summer in 55 patients and 55 matched healthy volunteers. Levels of melatonin were measured in plasma samples that were obtained every 30 minutes for 24 hours in each season. RESULTS: Patients and volunteers responded differently to change of season. In patients, the duration of the nocturnal period of active melatonin secretion was longer in winter than in summer (9.0 +/- 1.3 vs 8.4 +/- 1.3 hours; P=.001) but in healthy volunteers there was no change (9.0 +/- 1.6 vs 8.9 +/- 1.2 hours; P=.5). CONCLUSIONS: The results show that patients with seasonal affective disorder generate a biological signal of change of season that is absent in healthy volunteers and that is similar to the signal that mammals use to regulate seasonal changes in their behavior. While not proving causality, this finding is consistent with the hypothesis that neural circuits that mediate the effects of seasonal changes in day length on mammalian behavior mediate effects of season and light treatment on seasonal affective disorder.

Antidepressant drug-induced hypothalamic cooling in Syrian hamsters.

Antidepressant drugs have been reported to alter the circadian pattern of body temperature, but specific effects on the amplitude or on average body temperature are not consistent, and there have been no specific studies to examine chronic drug effects on brain temperature. To address these issues, hypothalamic temperature (Thy) was monitored telemetrically in hamsters treated with three antidepressant drugs: the monoamine oxidase inhibitor (MAOI), clorgyline; the 5HT reuptake inhibitor, fluoxetine; and the alkali metal, lithium. For comparison, hamsters were also treated with two neuroleptic drugs, chlorpromazine and haloperidol. Each of the three antidepressant drugs, but neither of the neuroleptic drugs, produced a chronic decrease in diurnal (rest-phase) hypothalamic temperature. The Thy-decreasing effect of clorgyline was not prevented by pinealectomy, and Thy decreased more than peritoneal temperature (Tp), thus reducing the temperature difference between the hypothalamus and the peritoneal cavity. Less general effects of the antidepressants were also observed. Clorgyline and fluoxetine, but not lithium, delayed the 24-hour rhythm of Thy. Clorgyline and lithium, but not fluoxetine decreased the average 24-hour Thy. The neuroleptics chlorpromazine and haloperidol decreased the amplitude of the 24-hour Thy rhythm. The fact that chronic antidepressant drugs, but not neuroleptic drugs, decrease Thy is consistent with their different neurotransmitter effects and clinical applications, and raises the possibility that their antidepressant property might be related to their capacity to decrease Thy during sleep.

Fluoxetine decreases brain temperature and REM sleep in Syrian hamsters.

The antidepressant drug, fluoxetine (FLX), a selective serotonin reuptake inhibitor, was administered to Syrian hamsters, and its acute and chronic effects on EEG sleep and hypothalamic temperature were recorded. Acute fluoxetine treatment at doses of 5, 10, 20 and 40 mg/kg decreased REM sleep and hypothalamic temperature in a dose-dependent manner. It increased NREM sleep, and, at doses of 20 and 40 mg/kg, it increased wakefulness. At 40 mg/kg, it decreased motor activity. During chronic treatment, tolerance developed to FLX's REM sleep-inhibiting effects, but tolerance did not develop to FLX's hypothalamic temperature-decreasing effects. Chronic FLX treatment produced circadian phase-dependent decreases in temperature beyond those that were observed during acute treatment. The apparent dissociation during chronic treatment between FLX's temperature-lowering effects and its REM-decreasing effects might be related to long-term changes in 5HT receptor function or FLX pharmacokinetics.

Single-dose treatment of uncomplicated gonorrhea: a comparison of cefonicid and penicillin.

Cefonicid, a parenteral semisynthetic cephalosporin, achieves high and sustained serum levels in humans. Activity against strains of Neisseria gonorrhoeae, including those that produce beta-lactamase, has been shown in vitro. The efficacy of 1.0 g of cefonicid was evaluated noncomparatively in 50 men with gonococcal urethritis; four failed to respond to treatment. Additionally, 57 men and 34 women received either 1.0 g of cefonicid or 4.8 X 10(6) units of procaine penicillin G plus 1.0 g of probenecid in a double-blind study. Among 17 men treated with penicillin, two failed to respond, and one failed among the 33 patients treated with cefonicid. Seventeen women received 1.0 g of cefonicid, and all cervical infections were cured. Among those who received cefonicid, 13 had rectal infections; and four had positive cultures at follow-up four to seven days posttreatment. Among the 17 women receiving penicillin, none failed to respond to therapy; only seven had both cervical and rectal infection. Of the 116 pretreatment and seven posttreatment isolates tested, 45 (37%) were inhibited by less than 0.0625 microgram of penicillin/ml and 121 (98%) were inhibited by less than 1.0 microgram/ml. Forty-one (33%) of the 123 isolates were inhibited by less than 0.0625 microgram of cefonicid/ml and 122 (99%) by less than 1.0 microgram of cefonicid/ml. The median MIC of cefonicid for the strains isolated from the women whose rectal infections were cured was 0.125 microgram/ml; that for the strains isolated from the women with rectal infections who failed to respond was 0.5 microgram/ml. Administration of 1.0 g of cefonicid intramuscularly is effective therapy for uncomplicated gonococcal urethritis in men.(ABSTRACT TRUNCATED AT 250 WORDS)

Trimethoprim-sulfamethoxazole in the treatment of gonorrhea: comparison with standard treatment schedules.

Several treatment regimens of trimethoprim-sulfamethoxazole (TMP-SMZ) were compared to the USPHS-recommended schedules for treatment of uncomplicated gonorrhea with ampicillin plus probenecid, tetracycline, or aqueous procaine penicillin G in both men and women. TMP-SMZ, six tablets as a single oral dose daily for 3 days, was as effective as the ampicillin or tetracycline schedules. The drug was well tolerated.

Treatment of gonorrhea with spectinomycin hydrochloride: comparison with standard penicillin schedules.

Spectinomycin hydrochloride, a new parenteral antibiotic prepared from Streptomyces spectabilis, was compared with standard U.S. Public Health Service-recommended dosages of aqueous procaine penicillin G in the treatment of uncomplicated gonorrhea in 353 men and 314 women. Of the 314 women, 130 had a pretreatment positive rectal culture. All diagnoses were proven by culture on Thayer-Martin selective medium. Minimal inhibitory concentrations of both drugs were determined. Single doses of 2 and 4 g of spectinomycin were compared with 2.4 million units of procaine penicillin in males and with both 2.4 and 4.8 million units of procaine penicillin in females. Both spectinomycin schedules, 2.4 million units of penicillin in males and 4.8 million units of penicillin in females, resulted in cure rates in excess of 90%. There were no failures at the rectal site only in those women with positive rectal cultures. There was no advantage to using the larger amount of spectinomycin in either sex.