High-dose daunorubicin in older patients with acute myeloid leukemia

BACKGROUND: A complete remission is essential for prolonging survival in patients with acute myeloid leukemia (AML). Daunorubicin is a cornerstone of the induction regimen, but the optimal dose is unknown. In older patients, it is usual to give daunorubicin at a dose of 45 to 50 mg per square meter of body-surface area. METHODS: Patients in whom AML or high-risk refractory anemia had been newly diagnosed and who were 60 to 83 years of age (median, 67) were randomly assigned to receive cytarabine, at a dose of 200 mg per square meter by continuous infusion for 7 days, plus daunorubicin for 3 days, either at the conventional dose of 45 mg per square meter (411 patients) or at an escalated dose of 90 mg per square meter (402 patients); this treatment was followed by a second cycle of cytarabine at a dose of 1000 mg per square meter every 12 hours [DOSAGE ERROR CORRECTED] for 6 days. The primary end point was event-free survival. RESULTS: The complete remission rates were 64% in the group that received the escalated dose of daunorubicin and 54% in the group that received the conventional dose (P=0.002); the rates of remission after the first cycle of induction treatment were 52% and 35%, respectively (P<0.001). There was no significant difference between the two groups in the incidence of hematologic toxic effects, 30-day mortality (11% and 12% in the two groups, respectively), or the incidence of moderate, severe, or life-threatening adverse events (P=0.08). Survival end points in the two groups did not differ significantly overall, but patients in the escalated-treatment group who were 60 to 65 years of age, as compared with the patients in the same age group who received the conventional dose, had higher rates of complete remission (73% vs. 51%), event-free survival (29% vs. 14%), and overall survival (38% vs. 23%). CONCLUSIONS: In patients with AML who are older than 60 years of age, escalation of the dose of daunorubicin to twice the conventional dose, with the entire dose administered in the first induction cycle, effects a more rapid response and a higher response rate than does the conventional dose, without additional toxic effects. (Current Controlled Trials number, ISRCTN77039377; and Netherlands National Trial Register number, NTR212.)

Juvenile myoclonic epilepsy with photosensitivity in a female with Velocardiofacial syndrome (del(22)(q11.2))--causal relationship or coincidence?

We report on an adolescent female with Velocardiofacial syndrome (del(22)(q11.2)) and an epilepsy phenotype resembling juvenile myoclonic epilepsy (JME). Clinically, the patient has characteristic signs of both disorders. JME has been linked to several chromosomes, but has not been related to 22q11.2 and is rarely observed in other genetic syndromes. We discuss possible explanations for a relationship between the chromosomal aberration and epilepsy as well as the importance of precise delineation of both epilepsy phenotypes and genetic defects in chromosomal disorders.

Cadherin-11 up-regulation in overactive bladder suburothelial myofibroblasts

PURPOSE: We investigated whether the adherens junction proteins cadherin-11 and beta-catenin can be immunohistochemically visualized in the human bladder using commercially available antibodies and, if so, whether there are differences between patients with overactive bladder and refractory detrusor overactivity, and controls without lower urinary tract symptoms. MATERIALS AND METHODS: In a prospective, nonrandomized single center study 32 patients with overactive bladder and refractory detrusor overactivity, and 8 controls without lower urinary tract symptoms underwent cystoscopic bladder biopsy. Quantitative immunohistochemistry was performed. The primary outcome was cadherin-11 and beta-catenin expression in the human bladder using commercially available antibodies. The secondary outcome was differences in cadherin-11 and beta-catenin in patients with overactive bladder and refractory detrusor overactivity, and controls. RESULTS: Double labeling experiments showed co-localization of cadherin-11 and connexin 43 in the suburothelium. There was also strong co-localization of cadherin-11 and beta-catenin in the suburothelium and detrusor. Significant 2-fold up-regulation of cadherin-11 was found in the suburothelium of patients with overactive bladder compared with that in controls (p = 0.018), whereas beta-catenin was similar in the groups (p = 0.6). In the detrusor cadherin-11 and beta-catenin expression was comparable in patients with overactive bladder and controls (each p = 0.5). No difference was observed in cadherin-11 and beta-catenin in patients with overactive bladder with idiopathic vs neurogenic detrusor overactivity in the suburothelium and the detrusor (p >0.3 and >0.2, respectively). CONCLUSIONS: Using commercially available antibodies cadherin-11 and beta-catenin expression in human bladder suburothelial myofibroblasts and detrusor smooth muscle cells was noted. Cadherin-11 up-regulation in suburothelial myofibroblasts in patients with overactive bladder may be significant in overactive bladder pathogenesis.

Verbreitung der Direktsaat in der Schweiz

Direktsaat ist eine wirksame Erosionsschutzmassnahme, die diverse ökologische und ökonomische Vorteile aufweist. Sie gewann in der Schweiz in den letzten Jahren zunehmend an Bedeutung: Seit Mitte der 1980er hat die direkt gesäte Fläche von wenigen Hektaren auf rund 12'000 ha im Jahre 2006 zugenommen. Gemessen am gesamten Ackerland ist diese Fläche aber nach wie vor gering (3 %). Regional kann die Direktsaat jedoch beachtliche Anteile aufweisen. Die in diesem Artikel vorgestellten Karten geben einen nationalen Überblick über die räumliche Verbreitung der direkt gesäten Fläche im Jahr 2006. Als Datengrundlage diente eine im Winter 2006 / 07 durchgeführte Befragung von Landwirten und Lohnunternehmern. Die Karten zeigen sehr heterogene Muster, machen aber auch verschiedene Schwerpunktregionen sichtbar. Die Interpretation dieser Muster veranschaulicht, dass die Verbreitung der Direktsaat an eine Vielzahl von Faktoren gebunden ist und nicht nur anhand naturräumlicher Gegebenheiten erklärt werden kann. Kantonale Förderprogramme spielen dabei eine ebenso wichtige Rolle wie das persönliche Engagement der beteiligten Experten und Lohnunternehmer, bestehende landwirtschaftliche Netzwerke sowie die Lebenswelten der Landwirte.