Laparoscopic ovarian cystectomy for a benign teratoma in a 10-year-old girl.

A 10-year-old girl was diagnosed with an 8-cm mature cystic teratoma. An outpatient ovary-conserving cystectomy was performed, and the girl recovered fully in 24 hours. We suggest that laparoscopy can be effective in the conservative management of some gynecologic disorders in properly selected children.

Laparoscopic hysterectomy for persistent gestational trophoblastic neoplasia.

We performed laparoscopic hysterectomy in a woman with persistent gestational trophoblastic neoplasia. The procedure offered advantages over vaginal hysterectomy in that intraabdominal inspection was possible, morcellation was avoided, and the uterine arteries were transected before uterine manipulation to avoid potential tumor embolization. In addition, an abdominal incision was not required, and the patient had shorter hospitalization and less pain than she would have had with the standard abdominal procedure. Persistent, locally invasive gestational trophoblastic neoplasia (GTN) develops in 15% of women after dilatation and evacuation for molar pregnancy. Chemotherapy and hysterectomy are curative in virtually all patients. Numerous factors are considered in deciding the primary mode of therapy. Women in whom fertility is not an issue may choose hysterectomy, which decreases the amount of chemotherapy required to achieve cure. Traditionally, this has been performed with an abdominal approach. We performed laparoscopic hysterectomy to manage GTN.

Biotransformation and pharmacokinetic overview of enoximone and its sulfoxide metabolite.

Enoximone possesses both positive inotropic and vasodilatory activities and may be useful in the treatment of patients with congestive heart failure (CHF). In all animal species investigated (rat, dog, monkey and man), the major urinary metabolite is the sulfide oxidation product (sulfoxide); very little unchanged drug appears in urine. Both in vitro and in vivo animal studies indicate reversibility of the sulfoxidation reaction; therefore, it is presumed that sulfoxidation is reversible in man. In normal healthy subjects, no difference in extent of absorption due to dietary state is observed. In patients with New York Heart Association class III to IV CHF, median terminal disposition half-lives for enoximone and its sulfoxide metabolite are 6.2 to 7.6 hours, respectively. Enoximone and sulfoxide plasma concentrations from high dose intravenous infusion studies in patients with class III to IV CHF were also investigated. The collective data suggest nonlinearity in one or more pharmacokinetic processes, of which one may be saturation of sulfoxidation. No direct relation between enoximone and/or the sulfoxide metabolite plasma concentration and pharmacologic effect has been established.

Acute hemodynamic effect of oral MDL 17,043 in severe congestive heart failure.

MDL 17,043, when administered intravenously in humans, produces a significant and salutary hemodynamic response. To determine its acute effect when administered orally (3 mg/kg), 10 patients with severe congestive heart failure were studied by right-sided cardiac catheterization for 8 hours. At 4 hours after drug ingestion, there was significant improvement in several hemodynamic measurements. Cardiac index increased 38% over baseline (from 1.9 +/- 0.4 to 2.6 +/- 0.4 liters/min/m2, p less than 0.01), arteriovenous oxygen difference decreased by 30% (from 8.0 +/- 1.4 to 5.6 +/- 1.2 vol%, p less than 0.01), heart rate increased by 8% (from 85 +/- 16 to 92 +/- 16 beats/min, p less than 0.05), stroke volume index increased by 22% (from 23 +/- 5 to 28 +/- 4 ml/beat/m2, p less than 0.05), left ventricular stroke work increased by 24% (from 18 +/- 5 to 22 +/- 5 g-m/m2, p less than 0.01), mean arterial pressure decreased by 10% (from 79 +/- 6 to 71 +/- 9 mm Hg, p less than 0.01), mean right atrial pressure decreased by 40% (from 10 +/- 5 to 6 +/- 4 mm Hg, p less than 0.01), and mean pulmonary artery wedge pressure decreased by 36% (from 22 +/- 5 to 14 +/- 6 mm Hg, p less than 0.01). Cardiac index, arteriovenous oxygen difference, mean arterial pressure, right atrial pressure, and pulmonary artery wedge pressure remained significantly improved at 8 hours. These findings indicate that MDL 17,043 is active when administered orally and produces beneficial hemodynamic effects for as long as 8 hours.

Simultaneous analysis of a new cardiotonic agent, MDL 17,043, and its major sulfoxide metabolite in plasma by high-performance liquid chromatography.

MDL 17,043 or 1,3-dihydro-4-methyl-5-[4-(methylthio)benzoyl]-2H-imidazol-2-one, is a new cardiotonic agent being developed for the treatment of congestive heart failure. This communication describes a sensitive and selective analytical procedure for the simultaneous analysis of MDL 17,043 and its major oxidative metabolite in plasma. The method involves addition of internal standard and organic solvent extraction, followed by separation with high-performance liquid chromatography and detection by ultraviolet absorption. The assay has good precision and accuracy. Evidence for the positive identification of the sulfoxide metabolite is also presented.

The objective and timing of drug disposition studies, appendix III. Diethylpropion and its metabolites in the blood plasma of the human after subcutaneous and oral administration.

Diethylpropion hydrochloride is an effective anorexiant at the recommended dose of 25 mg three times a day. Previous work in volunteers to evaluate the effects of much larger doses showed that 400 mg given orally was equipotent with 600 mg subcutaneously in terms of subjective and physiologic effects, i.e., the drug was more potent orally than subcutaneously. In one volunteer, blood level studies after a 600-mg subcutaneous dose showed concentrations of unchanged diethylpropion in the plasma about three times as high as those found after the equipotent 400 mg oral dose. In nine other volunteers, the plasma concentrations of unchanged diethylpropion found after a 75-mg oral dose was less than 1/100 of that observed after a 400-mg oral dose. These observations suggest a rapid but limited metabolic capacity for conversion of diethylpropion to its metabolites. The data indicate that the metabolites, rather than the parent drug, are responsible for the pharmacologic responses seen with doses much larger than those necessary for inducting anorexia.