Search

INTRODUCTION: Hypothalamic-pituitary-adrenal (HPA) axis activity is related to childhood disruptive behavior disorders and to exposure to abuse and neglect. This study explores the relationship of diurnal salivary cortisol levels with oppositional defiant disorder (ODD) and caregiver attitudes toward physical punishment among boys in Mongolia. METHODS: Salivary cortisol was collected in the home or institution 4 times daily for 4 days from 46 boys, aged 4-10 years, in Ulaanbaatar, Mongolia. Caregivers rated child disruptive behavior symptoms, attitudes toward physical punishment, and community violence exposures. Mixed effects models were used to estimate the association of psychopathology and caregiver attitudes with salivary cortisol levels. RESULTS: Boys meeting criteria for ODD displayed consistently lower diurnal salivary cortisol levels compared to boys without ODD diagnoses. Controlling for ODD diagnosis, boys with depression showed higher cortisol levels throughout the day. No other diagnosis was associated with cortisol levels. Psychiatric diagnosis accounted for 17% of between individual variations in cortisol levels unexplained by the covariates. In a separate model, caregivers' beliefs regarding physical punishment accounted for 11% of between individual differences: boys with caregivers who stated physical punishment was necessary for discipline displayed hypocortisolism. Institutionalization did not associate with cortisol levels. DISCUSSION: Salivary cortisol data from a non-Western naturalistic setting support an association of reduced basal HPA activity with disruptive behavior disorders and caregiver attitudes toward discipline. These findings suggest HPA functioning may be a reflection of or mediate disruptive behavior disorders in children across ethnic and cultural settings. Language: en

Temozolomide sensitivity is determined by methylation of the O6-methylguanine-DNA methyltransferase (MGMT) promoter. This study assessed whether the temozolomide dose can be tailored by MGMT promoter status and whether protracted, low-dose temozolomide can “prime” blasts in patients with unmethylated MGMT (unMGMT). Elderly patients with high-risk AML were stratified by MGMT methylation. Patients with methylated MGMT (mMGMT) received temozolomide 200 mg/m2 orally for 7 days every 4 weeks, while patients with unMGMT received temozolomide 100 mg/m2 orally for 14 days followed by 200 mg/m2 orally for 7 days every 6weeks. Of 36 patients (median age, 75 years), 31 (86%) had an unMGMT promoter. Overall response rate for the entire cohort was 36%. Patients with mMGMT and unMGMT had similar response rates (40% vs. 29%). Median duration of response and overall survival (OS) among responders were 29 and 35 weeks, respectively. Induction deaths (ID) occurred in 25% of patients, mostly caused by disease progression. Hematological toxicities were the most common adverse event. Toxicities were similar between patients on conventional versus protracted schedules. High HCT-CI scores were predictive of lower CR rate, higher ID, and shorter OS, while bone marrow blast count

The majority of patients with acute myeloid leukaemia (AML) are elderly. Advancements in supportive care and regimen intensification have resulted in improvements in clinical outcomes for younger AML patients, but analogous improvements in older patients have not been realized. While outcomes are compromised by increased comorbidities and susceptibility to toxicity from therapy, it is now recognized that elderly AML represents a biologically distinct disease that is more aggressive and less responsive to therapy. Some patients tolerate and benefit from intensive remission-induction approaches, while others are best managed with less aggressive strategies. The challenge is to differentiate these groups based on host-related and biological features, in order to maximize the therapeutic benefit and minimize toxicity. As more is understood about the complicated pathogenesis and molecular basis of AML, there are more opportunities to develop and test targeted therapies. Elderly patients, with their narrow therapeutic window, are well positioned to derive a benefit from these novel agents, and therefore, despite a difficult past, there are reasons to be optimistic about the future of elderly AML.

Background Sitagliptin is a new oral glucose-lowering medication that acts via the incretin hormone system. The most common side-effects are headache and pharyngitis, and few serious adverse events were observed during clinical trials. Dose adjustment is recommended in renal insufficiency, but long-term safety experience is limited. Case report We present a patient with chronic renal insufficiency who developed leg pain, weakness and tenderness after starting treatment with high-dose sitagliptin while on simvastatin. The patient had acute renal failure and rhabdomyolysis that resolved with cessation of sitagliptin, simvastatin, ezetimibe, diuretics and olmesartan. All drugs except sitagliptin, ezetimibe and simvastatin were resumed, and the patient was subsequently started on lovastatin without recurrence of rhabdomyolysis. Conclusions High doses of sitagliptin may have worsened this patient's renal failure and precipitated rhabdomyolysis by increasing circulating levels of simvastatin. Given the high likelihood that sitagliptin will be co-administered with statins and renally active medications, further study of long-term safety of sitagliptin in renal sufficiency may be warranted.