Efforts for the Correct Comprehension of Deceitful and Ironic Communicative Intentions in Schizophrenia: A Functional Magnetic Resonance Imaging Study on the Role of the Left Middle Temporal Gyrus.

Deficits in social cognition and more specifically in communication have an important impact on the real-life functioning of people with schizophrenia (SZ). In particular, patients have severe problems in communicative-pragmatics, for example, in correctly inferring the speaker's communicative intention in everyday conversational interactions. This limit is associated with morphological and functional alteration of the left middle temporal gyrus (L-MTG), a cerebral area involved in various communicative processes, in particular in the distinction of ironic communicative intention from sincere and deceitful ones. We performed an fMRI study on 20 patients with SZ and 20 matched healthy controls (HCs) while performing a pragmatic task testing the comprehension of sincere, deceitful, and ironic communicative intentions. We considered the L-MTG as the region of interest. SZ patients showed difficulties in the correct comprehension of all types of communicative intentions and, when correctly answering to the task, they exhibited a higher activation of the L-MTG, as compared to HC, under all experimental conditions. This greater involvement of the L-MTG in the group of patients could depend on different factors, such as the increasing inferential effort required in correctly understanding the speaker's communicative intentions, and the higher integrative semantic processes involved in sentence processing. Future studies with a larger sample size and functional connectivity analysis are needed to study deeper the specific role of the L-MTG in pragmatic processes in SZ, also in relation to other brain areas.

Increased tolerability of bimonthly 12-hour timed flat infusion 5-fluorouracil/irinotecan regimen in advanced colorectal cancer: A dose-finding study.

A dose-finding study was designed to determine the maximum tolerated dose (MTD) of a bimonthly 12-h (10:00 p.m to 10:00 a.m), timed flat infusion (TFI) of 5-fluorouracil (5-FU) plus irinotecan (CPT-11), without leucovorin (LV), for metastatic colorectal carcinoma (CRC). A total of 33 patients were treated. Seven dose levels included a fixed CPT-11 dose of 180 mg/m2 on days 1 and 15 (d(1,15)) and escalating doses of 5-FU 600-1200 mg/m2 on days 1-4 and 15-18 (d(1-4,15-18)). Dose-limiting toxicities (DLTs) were: grade 3-4 non-hematologic, grade 4 hematologic and any toxicity causing a more than a 2-week delay in treatment. The MTD was reached at the seventh dose level. DLTs were observed in 5/8 patients (63%): G3 diarrhea, 2 patients, associated with G3 mucositis in one instance; G4 neutropenia, 2 patients, associated with severe asthenia in 1 patient; G3 hand-foot syndrome, 1 patient. The recommended doses (RDs) were established at the sixth dose level: 5-FU, 1100 mg/m2/d(1-4,15-18); CPT-11 180 mg/m2/d(1,15) [5-FU and CPT-11 dose intensity (DI), 2200 and 90 mg/m2 per week (w), respectively]. At the recommended dose, the DLTs in 38 cycles were: mucositis, 2 cycles (5%); afebrile G4 neutropenia and hand-foot syndrome, 1 cycle (3%). In 24 assessable patients, the overall response rate was 37.5%. The present CPT-11/5-FU schedule is highly tolerable in an outpatient setting using the highest recommended 5-FU dose effective in advanced CRC.

Prophylactic options in patients with 5-fluorouracil-associated cardiotoxicity.

At present, the various mechanisms involved in 5-fluorouracil (5-FU)-correlated cardiotoxicity remain to be elucidated and a universally accepted prophylaxis or treatment for this specific toxicity is not available. Although it may improve time to progression, survival and clinical benefit, a 5-FU-based regimen usually has to be discontinued if a patient experiences cardiotoxicity. Here, we describe our experience with three cases of 5-FU-associated cardiotoxicity. The angina-like pain that appeared approximately 95 h after beginning 5-FU therapy was apparently independent of the drug's administration modality. In the two patients receiving 5-FU 12-h flat continuous infusion from 22.00 to 10.00 h (5-FU 12-h c.i.) in combination with other drugs, the dose of 5-FU was reduced by 10-20% and patients received prophylactic transepidermal nitroglycerin. In the third patient, 5-FU administration modality was changed and prophylactic therapy was not given. By taking these precautions, the patients no longer complained of anginal pain and none of them discontinued chemotherapy.