Uncertainty during anticipation modulates neural responses to aversion in human insula and amygdala.

Uncertainty about potential negative future outcomes can cause stress and is a central feature of anxiety disorders. The stress and anxiety associated with uncertain situations may lead individuals to overestimate the frequency with which uncertain cues are followed by negative outcomes, an example of covariation bias. Using functional magnetic resonance imaging, we found that uncertainty-related expectations modulated neural responses to aversion. Insula and amygdala responses to aversive pictures were larger after an uncertain cue (that preceded aversive or neutral pictures) than a certain cue (that always preceded aversive pictures). Anticipatory anterior cingulate cortex (ACC) activity elicited by the cues was inversely associated with the insula and amygdala responses to aversive pictures following the cues. Nearly 75% of subjects overestimated the frequency of aversive pictures following uncertain cues, and ACC and insula activity predicted this uncertainty-related covariation bias. Findings provide the first evidence of the brain mechanisms of covariation bias and highlight the temporal dynamics of ACC, insula, and amygdala recruitment for processing aversion in the context of uncertainty.

Effect of hemodialysis on topotecan disposition in a patient with severe renal dysfunction.

The pharmacokinetics of topotecan have been extensively studied in patients with normal renal function and there is one study of patients with mild to moderate renal insufficiency. However, the effect of hemodialysis on topotecan disposition has not been reported. The objective of this study was to characterize the disposition of topotecan in a patient with severe renal insufficiency receiving hemodialysis. Topotecan lactone disposition was characterized in a patient on and off hemodialysis. The topotecan lactone clearance determined after administration of topotecan alone and with hemodialysis was 5.3 l/h per m(2) vs 20.1 l/h per m2 respectively. At 30 min after the completion of hemodialysis, the topotecan plasma concentration obtained was greater than that measured at the end of hemodialysis (i.e. 8.0 ng/ml vs 4.9 ng/ml), suggesting a rebound effect. The topotecan terminal half-life off dialysis was 13.6 h, compared with an apparent half-life determined during hemodialysis of 3.0 h. These results demonstrate that topotecan plasma clearance while on hemodialysis increased approximately fourfold. Hemodialysis may be an effective systemic clearance process for topotecan and should be considered in selected clinical situations (e.g. inadvertent overdose, severe renal dysfunction).

Randomized, multicenter comparison of oral granisetron and oral ondansetron for emetogenic chemotherapy.

STUDY OBJECTIVES: To compare the antiemetic effectiveness and safety of oral granisetron plus dexamethasone with those of oral ondansetron plus dexamethasone administered before emetogenic chemotherapy. DESIGN: Randomized, prospective, multicenter, open-label study. SETTINGS: University-teaching hospital and veterans health care system. PATIENTS: Sixty-one chemotherapy-naïve patients scheduled to receive emetogenic antineoplastic agents. INTERVENTION: A single-dose oral granisetron 1 mg and dexamethasone 12 mg or single-dose oral ondansetron 16 mg and dexamethasone 12 mg was administered before chemotherapy. MEASUREMENTS AND RESULTS: Twenty-four hours after administration patients were contacted to assess nausea, emesis, and adverse events. There were no statistical differences in frequency of nausea or emesis between groups. Seventy-six percent and 82% of patients receiving ondansetron and granisetron, respectively, experienced no emesis 24 hours after chemotherapy. Complete protection from nausea occurred in 58% and 46% of patients receiving the drugs, respectively. Adverse events were similar between groups. CONCLUSION: Oral granisetron 1 mg and ondansetron 16 mg plus dexamethasone are safe and effective in preventing nausea and vomiting related to emetogenic chemotherapy.

Severe necrosis due to paclitaxel extravasation.

Paclitaxel is an antineoplastic agent derived from the bark of the Pacific yew tree that has activity against many tumors including breast and ovarian carcinomas. In the past, its extravasation quality has been considered to be a local irritant; however, recent reports suggest that the agent may be a vesicant. A patient experienced a delayed vesicant reaction to a paclitaxel extravasation that resulted in severe necrosis. No acute symptoms were reported at the time of extravasation from the 24-hour peripheral paclitaxel infusion. However, on day 11 the patient complained of severe and progressive pain at the site of extravasation. The site was erythematous and had areas of central necrosis requiring debridement and closure by a plastic surgeon. Because paclitaxel possesses vesicant characteristics, health care professionals should be aware of its potential extravasation hazard. Prolonged peripheral infusions should be avoided or administered with extreme caution.

Chemical pleurodesis with doxycycline 1 g.

We evaluated the utility of a single 1-g dose of doxycycline in the treatment of malignant and nonmalignant pleural effusions and refractory pneumothoraces in 27 consecutive patients requiring pleurodesis. After the evacuation of all retained air or fluid, and premedication with intravenous narcotic analgesics and intrapleural lidocaine 200 mg, the patients received doxycycline 1 g in 50 ml normal saline instilled through the chest tube. This was followed by instillation of 100-200 ml of air to facilitate dispersion. The chest tube was removed when the drainage was less than 150 ml/day. Twenty-three of 27 patients were evaluated at 30 days. Six (67%) of the nine patients with pneumothoraces achieved a response, and both patients with nonmalignant pleural effusions had a complete response. Of the 12 patients with malignant pleural effusion, 8 (67%) achieved a complete response, 2 had a partial response, and 2 had no response. Twenty-two (81%) of 27 patients experienced adverse effects with pleurodesis, with pain (81%) and fever (11%) being the most prevalent. In this limited number of patients, doxycycline 1 g appeared to be safe and effective for the treatment of pleural effusions and pneumothoraces. The 1-g dose must be compared with the standard 500-mg dose and with other established agents.

Cytomegalovirus colitis after 5-fluorouracil and interferon-alpha therapy.

Cytomegalovirus (CMV) infection is an opportunistic viral infection primarily affecting immunocompromised patients. Patients with inflammatory bowel disease have an increased risk for developing CMV infections of the gastrointestinal tract. While receiving continuous infusion of 5-fluorouracil and interferon-alpha, a 72-year-old woman with stage IV pancreatic carcinoma developed severe colitis with diarrhea that was refractory to conventional antidiarrheals. A biopsy specimen from the colon revealed CMV inclusions, which were confirmed by immunofluorescence. The patient was given ganciclovir 210 mg (5 mg/kg) every 12 hours for 14 days, and the diarrhea resolved after approximately 8 days of therapy. This is the first reported case of CMV colitis associated with combination 5-fluorouracil and interferon-alpha therapy.