Effects of trichloroethylene and its metabolite trichloroacetic acid on the expression of vimentin in the rat H9c2 cell line.

Trichloroethylene (TCE) and its metabolite trichloroacetic acid (TCAA) are environmental contaminants with specific toxicity for the embryonic heart. In an effort to identify the cellular pathways disrupted by TCE and TCAA during heart development, we investigated their effects on expression of vimentin, a marker of cardiac differentiation. Previous studies had shown that the level of vimentin transcript was inhibited in rat embryonic heart after maternal exposure to TCE via drinking water. In the same study, maternal exposure to TCAA produced the opposite effect, inducing an increased level of vimentin mRNA. In this study, we selected an in vitro system, the rat cardiac myoblast cell line H9c2, to further characterize the molecular mechanisms used by TCE and TCAA to disrupt normal heart development. In particular, we investigated the effects of both toxicants on vimentin, at both the RNA and protein levels, using dose-response and time course curves. Our experimental findings indicate that vimentin expression is affected by TCE and TCAA in H9c2 cells similarly as in vivo. The work is significant because it provides a suitable in vitro model for studies looking at toxicant effects on myocardiac cells, and it suggests that vimentin is a good marker of TCE exposure in the embryonic heart.

Atovaquone suspension for treatment of Pneumocystis carinii pneumonia in HIV-infected patients.

OBJECTIVE: To describe clinical experience with atovaquone suspension for the treatment of Pneumocystis carinii pneumonia (PCP) in HIV-infected patients. DESIGN: A retrospective chart review. METHODS: The medical records of 54 HIV-infected patients with PCP treated with atovaquone were examined. The outcomes of 34 patients treated with atovaquone suspension (750 mg twice a day) were compared with those of 20 patients treated with atovaquone tablets (750 mg three times a day). RESULTS: The proportion of patients successfully treated was similar with the suspension (74%) and tablet (70%) formulations of atovaquone. The proportion of patients with an inadequate response to therapy was lower for patients treated with atovaquone suspension (15%) than tablets (30%). Both formulations were well tolerated. CONCLUSION: Atovaquone suspension is effective and well tolerated for the treatment of PCP.

Oral atovaquone compared with intravenous pentamidine for Pneumocystis carinii pneumonia in patients with AIDS. Atovaquone Study Group.

OBJECTIVE: To test the hypothesis that the therapeutic success rate of oral atovaquone is not worse than that of intravenous pentamidine in the primary treatment of mild and moderate Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome and to detect differences in the toxicity rates of the two treatments. DESIGN: Patients were randomly assigned to receive 21 days of open-label therapy with either atovaquone, 750 mg orally with meals three times daily, or intravenous pentamidine, 3 to 4 mg per kg body weight once daily. SETTING: Multicenter study including university and community treatment facilities. PATIENTS: Patients with human immunodeficiency virus infection and clinical presentations consistent with mild or moderate P. carinii pneumonia were eligible. For efficacy and safety analyses, patients with histologically confirmed P. carinii pneumonia were emphasized. MEASUREMENTS: Patients were monitored by clinical and laboratory evaluations for therapeutic efficacy and adverse events during the acute treatment phase and for 8 weeks after therapy was discontinued. RESULTS: As initial therapy for a histologically confirmed episode of P. carinii pneumonia, 56 patients received atovaquone and 53 received pentamidine. More patients were successfully treated with atovaquone (57%) than with pentamidine (40%), a difference of 17% (95% CI, -3% to 38%; P = 0.085), but more patients failed to respond to atovaquone (29%) than to pentamidine (17%), a difference of 12% (CI, -6% to 29%; P = 0.18). Discontinuation of original therapy because of treatment-limiting adverse events was more frequent in the pentamidine group (36%) than in the atovaquone group (4%) (difference, -32%; CI, -48% to -17%; P < 0.001). Nine patients in each treatment group died during the study. CONCLUSIONS: Oral atovaquone and intravenous pentamidine have similar rates for successful treatment of mild and moderate P. carinii pneumonia, but atovaquone has significantly fewer treatment-limiting adverse events.