Irinophore C?, a lipid-based nanoparticulate formulation of irinotecan, is more effective than free irinotecan when used to treat an orthotopic glioblastoma model

Given compelling evidences supporting the therapeutic potential of irinotecan (IRN) for patients with glioblastoma (GBM), the present study evaluated the activity of Irinophore C? (IrC?), a lipid-based nanopharmaceutical formulation of IRN, in GBM. The levels of IRN and SN-38 were determined in plasma and brain after a single intravenous dose of IRN or IrC? in tumor-free mice. Treatment with IrC? significantly increased the plasma AUC(0-24h) of the active (lactone) forms of IRN and SN-38 when compared to free drug (760 and 30-fold increase, respectively). Levels of IRN and SN-38 in brain tissue were also increased significantly (compared to IRN treatment) following IrC? administration. A tolerability study revealed that IrC? is better tolerated than IRN. The efficacy of IrC? and IRN was assessed in an orthotopic model of GBM. The therapeutic efficacy of IrC? given at 25mg/kg weekly was comparable to the efficacy achieved using twice the dose of IRN. At the maximum tolerated dose, IrC? (100mg/kg) increased the survival time of tumor-bearing mice of 83% compared to untreated animals. Ki67 immunostaining analysis of IrC?-treated tumors revealed a transient increase in cell proliferation after treatment. The results justify further studies evaluating the use of IrC? for treating GBM.     

Relationships between auditory event‐related potentials and mood state,medication, and comorbid psychiatric illness in patients with bipolar disorder

Background: Patients with bipolar disorder (BD) exhibit aberrations in auditory event‐related potentials (ERPs), although the relationships between these measures and mood state at testing, comorbid psychiatric illness, presence of psychotic features, and medication usage are unclear. The purpose of this study was to investigate the relationships between these factors and auditory ERP measures in BD patients. Methods: An auditory ‘oddball’ discrimination task was used to elicit ERPs from 69 patients with type I BD and 52 healthy controls. Patients were placed into subgroups based upon their mood state at testing (euthymic or symptomatic), and ANOVA was used to compare amplitude and peak latency measures from the N100, P200, N200, and P300 ERP components across subgroups. Multiple regression was used to investigate relationships between ERP measures and comorbid psychiatric diagnosis, history of psychotic features, and medication status. Results: Relative to healthy control participants, euthymic and symptomatic BD patients exhibited reduced P300 and P200 amplitude, but ERP measures did not differ among BD patients on the basis of mood status. A history of a comorbid anxiety disorder was associated with reduced N200 peak latency, but prolonged P300 peak latency among BD patients. No other relationships between clinical variables and ERP measures were significant. Conclusions: The results suggest that disrupted auditory attention may be observed in BD patients regardless of their mood state at testing, medication status, or history of psychosis. These results extend previous findings, and provide further evidence for aberrations in the P300 ERP as an endophenotype for BD.     

Spontaneous thrombosis of giant cavernous internal carotid artery aneurysm in a neonate. Case report and review of the literature

Neonatal intracranial aneurysms are rare, with only 20 cases being reported in the literature. No case of spontaneous resolution of a giant intracranial cavernous segment aneurysm in a neonate is reported till date. The authors describe a 3-week-old male child who presented with a left-sided tonic seizure episode and was diagnosed as having a right-sided giant cavernous internal carotid artery aneurysm. The aneurysm was found to be totally thrombosed on angiography done before planning definitive treatment. The child is doing well at 2 years of follow-up. Spontaneous thrombosis, an exceptionally rare but fortunate outcome in a rare case of giant neonatal internal carotid artery aneurysm, has led the authors to report this case. The need of repeat imaging or angiography should be considered to rule out this rare outcome, more so if there is any delay between the ictus and treatment.     

Exploring Coping Strategies Among Young Asian American Women Breast Cancer Survivors

In recent years, breast cancer rates among young Asian American women have been increasing. Despite increases in breast cancer among young Asian American women, little is known about how this population copes throughout diagnosis, treatment, and survivorship. This study was a qualitative exploration of how young Asian American women cope with breast cancer diagnosis, treatment, and survivorship. In-depth interviews with 22 young (under the age of 50) Asian American women diagnosed with early stage breast cancer were conducted. Through qualitative data analysis, three major themes emerged including moving from managing the emotions of others to expressing emotional vulnerability, moving from work and productivity to work-life balance, and moving beyond the family and reaching out to breast cancer survivors. At diagnosis, participants worked to maintain normalcy including caring for others and working during treatment. Once treatment was over, women worked to find ways to use their experience as a transformative one and also to develop more positive coping skills including expressing emotional vulnerability and reaching out to others. Further studies are needed to create and test culturally tailored supportive interventions that enhance positive coping tools among young Asian American women diagnosed by breast cancer.     

The time dose fractionation (TDF) relationship in the radiotherapy of carcinoma of the cervix

A retrospective analysis of 291 patients with cancer of the uterine cervix treated with a combination of external and intracavitary radiotherapy was carried out. Patients were either treated with 45 Gy in 20 fractions by five fractions per week or with 42 Gy in 14 fractions by three fractions per week schedule by external radiotherapy. For brachytherapy the total dose was 24 to 32 Gy at a dose rate of 1.4 to 2.2 Gy per hour. Treatment results in terms of response, survival, recurrence and complication were correlated with total TDF values for point A (TDFTA) and for rectum TDFTR. Correlations of TDFTA with overall complication rate (p value less than 0.05) and rectal complications rate (p value less than 0.01) were excellent. TDFTA values did not correlate with response, recurrence and survival rates (p value greater than 0.1). Lack of correlation was observed between TDFTR and overall complication rate (p value greater than 0.1) as well as rectal complication rate (p value greater than 0.1). In order to limit grade II and III rectal and bladder complications to acceptable level, in combined external and intracavitary treatments, TDFTA value of less than 150 is suggested.