Total percentage body weight changes during add-on therapy with tiagabine, carbamazepine and phenytoin.

Changes in body weight were evaluated in 349 patients from a study comparing efficacy of add-on therapy with tiagabine (TGB), carbamazepine (CBZ) or phenytoin (PHT). TGB add-on therapy showed no significant weight changes when added to either PHT or CBZ. CBZ add-on therapy showed a significant percentage weight gain of a mean body increase of 1.5% (P = 0.002). Adjunctive TGB therapy had no significant effect on total body weight, while adjunctive CBZ therapy was associated with weight gain.

Migraine prophylaxis with divalproex.

OBJECTIVE: To compare the effectiveness and safety of divalproex sodium (Depakote) and placebo in the prophylaxis of migraine headache. DESIGN: Multicenter, double-blind, randomized, placebo-controlled investigation, having a 4-week, single-blind placebo baseline phase and a 12-week treatment phase (4-week dose adjustment, 8-week maintenance). SETTING: Eight headache/neurology clinics throughout the United States. PATIENTS: One hundred seven patients randomized to divalproex or placebo (2:1 ratio): 70 receiving divalproex and 37 receiving placebo. INTERVENTION: Divalproex and placebo dosages titrated in blinded fashion during dose adjustment period to achieve actual/sham trough valproate sodium concentrations of approximately 70 to 120 mg/L. MEASUREMENTS AND MAIN RESULTS: During the treatment phase, the mean migraine headache frequency per 4 weeks was 3.5 in the divalproex group and 5.7 in the placebo group (p < or = .001), compared with 6.0 and 6.4, respectively, during the baseline phase. Forty-eight percent of divalproex-treated patients and 14% of placebo-treated patients showed a 50% or greater reduction in migraine headache frequency from the baseline phase (P < .001). Among those with migraine headaches, divalproex-treated patients reported significantly less functional restriction than placebo-treated patients and used significantly less symptomatic medication per episode. No significant treatment group differences were observed in average peak severity or duration of individual migraine headaches. Treatment was stopped in 13% of divalproex-treated patients and 5% of placebo-treated patients because of intolerance (P, not significant). CONCLUSIONS: Divalproex is an effective prophylactic drug for patients with migraine headaches and is generally well tolerated.

Single- and multiple-dose pharmacokinetics of clarithromycin, a new macrolide antimicrobial.

The pharmacokinetics of clarithromycin and its active 14(R)-hydroxy metabolite were evaluated after single and multiple oral doses of 250 and 500 mg of clarithromycin. Multiple-dose regimens used 12-hour dosing intervals for 7 doses. Plasma and urine concentrations were measured using high-performance liquid chromatography. Appearance of clarithromycin and its metabolite in plasma were rapid, as reflected by mean times to maximum plasma concentration ranging from 1.8 to 2.6 and 1.8 to 2.9 hours, respectively. The rises in clarithromycin peak plasma concentration (Cmax) and area under the plasma concentration versus time curve (AUC) were disproportionate to increase in dose, suggesting nonlinearity in parent compound pharmacokinetics. Clarithromycin terminal disposition half-life (t1/2) also exhibited dose dependency, ranging from harmonic means of 2.7 to 4.8 hours. In contrast, based on Cmax AUC, and predicted/observed accumulation ratios, nonlinearity in metabolite pharmacokinetics was not observed. Plasma accumulation of metabolite occurred to a much lesser degree than that of the parent compound despite a substantially longer t1/2 for the metabolite (metabolite accumulation ratios based on AUC dose 7/AUC dose 1:250-mg regimen = 1.03 +/- 0.33, 500-mg regimen = 0.81 +/- 0.29, parent accumulation ratios: 250-mg regimen = 1.64 +/- 0.47, 500-mg regimen = 1.65 +/- 0.69). This would suggest that formation of this metabolite is capacity-limited and that this may in part account for the nonlinearity observed in clarithromycin pharmacokinetics. Urinary excretion constituted a relatively important route of elimination of clarithromycin, with renal clearance accounting for 17 to 31% of apparent total body clearance.

Massive ovarian edema. A clinicopathologic study of five cases including ultrastructural observations and review of the literature.

Massive ovarian edema is a tumor-like condition occurring in young women considered to be the result of torsion of the ovary to the extent that it interferes with venous and lymphatic drainage, but is insufficient to cause necrosis. Marked enlargement of the ovary occurs, and the patient usually presents with an adnexal mass. If the torsion occurs acutely abdominal pain is prominent. If it occurs gradually, the patient may be virilized and stromal luteinization is often observed microscopically within the involved ovary. Edema fluid accumulates in the stroma but the tunica albuginea and superficial cortical zone are characteristically uninvolved. In one patient, precocious puberty was the presenting finding and this regressed following excision of the mass. This unique finding suggests that the lesion can result in the production of significant quantities of estrogen, and that this is less likely to be recognized after menarche. In the case studied by electron microscopy, the principal finding was the presence of both fibroblasts and myofibroblasts in the edematous stroma. The increased number of myofibroblasts may be a response to the edema.