BACKGROUND. Temozolomide (TMZ), an oral methylating imidazotetrazinone, has antitumor activity against gliomas, malignant melanomas, and brain metastasis and is presently administered as a 5‐day oral schedule every 4 weeks. METHODS. A single‐institution phase 2 clinical trial was conducted to determine the efficacy and the safety profile of a new regimen based on a dose‐intensified, protracted course of TMZ after whole‐brain radiotherapy (WBRT). Patients were eligible if they had at least 1 bidimensionally measurable brain metastasis from breast cancer and nonsmall cell lung cancer (NSCLC). Twenty‐seven patients were treated with 30 grays (Gy) of WBRT with concomitant TMZ (75 mg/m2/day) for 10 days, and subsequent TMZ at a dose of 75 mg/m2 per day for 21 days every 4 weeks, for up to 12 cycles. RESULTS. Two complete responses (7.4%) and 11 partial responses (40.7%) were achieved. The schedule appeared to be well tolerated, with grade 3 toxicity (graded according to National Cancer Institute Common Toxicity Criteria) observed in only 2 patients. The overall median survival was 8.8 months and the median progression‐free survival was 6 months. CONCLUSIONS. The concomitant use of WBRT and protracted low‐dose TMZ appears to be an active, well‐tolerated regimen. The observed antitumor activity suggests the need for further investigation of this schedule in combination with other anticancer agents for the concomitant treatment of brain metastases and primary cancers. Cancer 2008. © 2008 American Cancer Society.

Objective. Psychological interventions reduce the impact of psychosis, but widescale implementation is problematic. We tested the feasibility of group acceptance and commitment therapy for Psychosis (G-ACTp), delivered by frontline staff, and cofacilitated by service-user experts-by-experience (SU-EbyE), for service-users and informal caregivers (ISRCTN: 68540929). We estimated recruitment/retention rates and outcome variability for future evaluation. Methods. Staff and SU-EbyE facilitators completed 1-day workshops, then delivered closely supervised G-ACTp, comprising four sessions (weeks 1-4) and two boosters (10 and 12 weeks). Participants recruited from adult community psychosis services were randomized to receive G-ACTp immediately or after 12 weeks, completing outcome assessments at 0, 4, and 12 weeks. Service-use/month was calculated for 1-year prerandomization, weeks 0-12, and 5-year uncontrolled follow-up. Results. Of 41 facilitators trained (29 staff, 12 SU-EbyE), 29 (71%; 17 staff, 12 SU-EbyE) delivered 18 G-ACTp courses. Participant refusal rates were low (9% of service-users [10/112]; 5% of caregivers [4/79]); 60% of those invited to participate attended ≥1 G-ACTp session (64% of service-users [39/61]; 56% of caregivers [35/63]). Randomization of facilitators and participants proved problematic and participant follow-up was incomplete (78% [66/85]; 82% of service-users [36/44]; 73% of caregivers [30/41]). Effect

AimTo measure the prevalence of abnormal rest perfusion in a population of consecutive patients with known hypertrophic cardiomyopathy (HCM) referred for cardiovascular MRI (CMR), and to assess any associations between abnormal rest perfusion and the presence, pattern, and severity of myocardial scar and the presence of risk factors for sudden death.Materials and methodsEighty consecutive patients with known HCM referred for CMR underwent functional imaging, rest first-pass perfusion, and late gadolinium enhancement (LGE).ResultsThirty percent of the patients had abnormal rest perfusion, all of them corresponding to areas of mid-myocardial LGE and to a higher degree of segmental hypertrophy. Rest perfusion abnormalities correlated with more extensive and confluent LGE. The subgroup of patients with myocardial fibrosis and rest perfusion abnormalities (fibrosis+/perfusion+) had more than twice the incidence of episodes of non-sustained ventricular tachycardia on Holter monitoring in comparison to patients with myocardial fibrosis and normal rest perfusion (fibrosis+/perfusion–) and patients with no fibrosis and normal rest perfusion (fibrosis–/perfusion–).ConclusionsFirst-pass perfusion CMR identifies abnormal rest perfusion in a significant proportion of patients with HCM. These abnormalities are associated with the presence and distribution of myocardial scar and the degree of hypertrophy. Rest perfusion abnormalities identify patients with increased incidence of episodes of non-sustained ventricular tachycardia on Holter monitoring, independently from the presence of myocardial fibrosis.

The Italian Co-operative Group GIMEMA conducted a randomized trial in adult acute nonlymphocytic leukemia (ANLL) to assess the role of postconsolidation treatment. Of 448 evaluable patients entered into the study, 305 (68%) achieved a complete remission after a standard induction with daunorubicin and cytosine arabinoside (3 + 7; 2 + 5). Those in remission after a consolidation therapy including 4 courses of daunorubicin, cytosine arabinoside, and 6-thioguanine (DAT) were allocated to one of three arms: no treatment, conventional maintenance, or intensive postconsolidation therapy. The median disease-free survival (DFS) was 13 months, and the median survival was 14 months, with 26% surviving at 6.5 years. There was no difference in survival and in disease-free survival among the three postconsolidation arms. In conclusion our study, as others, suggests that the critical period of ANLL treatment is within the first 5-6 months.

A high oxygen affinity hemoglobin variant was identified in a 53-year-old male patient from Napoli (Italy), suffering from pulmonary thromboembolism and polycythemia. A detailed structural characterization of the variant hemoglobin was carried out, both at the protein and DNA levels, by a combination of DNA sequencing and allele-specific amplification techniques with mass spectrometric procedures. The amino acid substitution was found to be Tyr-->Cys, and the corresponding DNA mutation was identified as A-->G at the second position of codon 145 of the beta chain. These variations indicated the presence of Hb Rainier. Haplotype analysis of DNA polymorphisms showed that the beta-globin gene from Hb Rainier was associated with haplotype II. Moreover, structural analyses provided direct identification of an intramolecular disulphide bridge joining the newly inserted beta145Cys with beta93Cys. This is the first report of the occurrence of Hb Rainier in Italy.