A B S T R A C T The metabolism of acetone was studied in lean and obese humans during starvation ketosis. Acetone concentrations in plasma, urine, and breath; and rates of endogenous production, elimination in breath and urine, and in vivo metabolism were determined. There was a direct relationship between plasma acetone turnover (20-77 ,Umol/m2 per min) and concenitration (0.19-1.68 mM). Breath and urinary excretion of acetone accounted for a 2-30% of the endogenous production rate, and in vivo metabolism accounted for the remainder. Plasma acetone oxidation accounted for -60% of the production rate in 3-d fasted subjects and about 25% of the production rate in 21-d fasted subjects. About 1-2% ofthe total CO2 production was derived from plasma acetone oxidation and was not related to the plasma concentration or production rate. Radioactivity from [14C]acetone was not detected in plasma free fatty acids, acetoacetate, ,-hydroxybutyrate, or other anionic compounds, but was present in plasma glucose, lipids, and proteins. If glucose synthesis from acetone is possible in humans, this process could account for 11% of the glucose production rate and 59% of the acetone production rate in 21-d fasted subjects. During maximum acetonemia, acetone productioni from acetoacetate could account for 37% of the anticipated acetoacetate production, which implies that a significant fraction of the latter compound does not undergo immediate terminal oxidation.

A B S T R A C T Plasma acetate turnover and oxidation were determined in 11 healthy subjects by the constant infusion of a trace amount of [1_-4C]acetate for 6 h. The subjects ages ranged from 22 to 57 yr. There was a positive correlation (P < 0.001) between plasma acetate concentration and turnover rate, and a negative correlation (P < 0.001) between turnover and age. The plasma acetate concentration in the subjects 22-28 yr old was 0.17 vs. 0.13 mM (P < 0.02) in subjects 40-57 yr old. The plasma acetate turnover rate was also greater in the younger age group (8.23+0.66 vs. 4.98+0.64 ,umol/ min -kg, P < 0.01). Approximately 90% of the plasma acetate turnover was immediately oxidized to CO2 in both age groups, however, 13.2±+0.89% of the CO2 output in the younger group was derived from plasma acetate oxidation compared to 7.9+0.94% in the older group (P < 0.01). The mean plasma acetate concentration, turnover, and oxidation in six cancer patients 47-63 yr old were similar to the values observed in the age-matched healthy subjects.

Dronabinol (Marinol, Roxane Laboratories, Columbus, OH) and prochlorperazine were tested alone and in combination in a randomized, double-blind, parallel group, multicenter study. Patients were randomized to receive either 1) dronabinol 10 mg every 6 hr plus placebo; 2) placebo plus prochlorperazine 10 mg every 6 hr; or 3) dronabinol and prochlorperazine, each 10 mg every 6 hr. Antiemetic treatment was begun 24 hr prior to and continued for 24 hr after the last dose of chemotherapy; all was given orally. Only 29% of patients in group 3 versus 47% in group 1 and 60% in group 2 experienced nausea after chemotherapy. In addition, the median duration per episode and severity of nausea were significantly less with combination therapy. Vomiting occurred after chemotherapy in 41%, 55%, and 35% of patients in groups 1, 2, and 3, respectively. The median duration per episode of vomiting was 1 min in group 3 versus two in group 1 and four in group 2. Side effects, primarily CNS, were more common in group 1 than in group 2; addition of prochlorperazine to dronabinol appeared to decrease the frequency of dysphoric effects seen with the latter agent. The combination was significantly more effective than was either single agent in controlling chemotherapy-induced nausea and vomiting.

Using interference-contrast microscopy, erythrocyte vacuoles can be rapidly and easily distinguished. Because of the shadowing effect inherent in this optical system they appear as surface indentations. Twenty splenectomized patients with both normal and abnormal erythropoiesis had 54.3 per cent vacuolated cells as compared to 2.1 per cent in a control group of normal adults. A splenectomized patient with pure red cell aplasia, whose erythrocyte mass was maintained with fresh normal blood, had 44 per cent vacuolated cells. Electron microscopy thin sections showed numerous erythrocyte inclusions and vacuoles which were morphologically suggestive of hemoglobin degeneration. Similar inclusions were noted in all splenectomized subjects studied, and were found in greater numbers in patients with young cell populations. They were rare in normals with intact spleens. Transfusion studies show that these inclusions can be acquired by normal mature erythrocytes when circulating in an asplenic patient. Further, they are cleared from the circulation in the presence of an intact spleen without measurable loss of red cell viability. The evidence suggests that, in the absence of a spleen, autophagic vacuoles may occur in situ in all circulating red cells. It is presumed that these inclusions would normally be removed as a physiological process by a functioning spleen.

Paclitaxel plus carboplatin is an active and tolerable outpatient treatment for patients with advanced carcinoma of the urothelium. The ability to administer this combination over multiple cycles even to patients with advanced age and abnormal renal function makes it well suited for this patient population. Confirmatory trials of this regimen are ongoing.

Toremifene has antiestrogenic and estrogenic properties in vitro and in vivo. In addition, it may have antiangiogenesis and antimicrotubule properties at higher doses. Studies have demonstrated the efficacy of this agent in the treatment of metastatic breast cancer. We performed a phase II trial of toremifene in patients with androgen-independent prostate cancer (AIPC). Patients with an increasing prostate-specific antigen level despite castrate testosterone levels and antiandrogen withdrawal were eligible. Patients could not have received prior salvage hormonal therapy or chemotherapy. Patients received toremifene at 300 mg/m2/d orally (maximum dose 640 mg/d). Fifteen patients were treated. Patients received treatment for a median of 13 weeks (range, 4-30 weeks). The median age was 72 years (range, 58-80 years). The median Eastern Cooperative Oncology Group performance status was 0. The treatment was well tolerated and toxicity was mild. Two patients had grade III hepatic toxicity; one had grade III hyperglycemia. There were no treatment-related deaths. No objective responses were demonstrated. In summary, toremifene is not effective therapy for AIPC at the dose and schedule evaluated in this trial.

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