Randomised,open-label,phase II study of gemcitabine with and without IMM-101 for advanced pancreatic cancer

Background:

Immune Modulation and Gemcitabine Evaluation-1, a randomised, open-label, phase II, first-line, proof of concept study ({"type":"clinical-trial","attrs":{"text":"NCT01303172","term_id":"NCT01303172"}}NCT01303172), explored safety and tolerability of IMM-101 (heat-killed Mycobacterium obuense; NCTC 13365) with gemcitabine (GEM) in advanced pancreatic ductal adenocarcinoma.

Methods:

Patients were randomised (2 : 1) to IMM-101 (10 mg ml^−l intradermally)+GEM (1000 mg m⁻² intravenously; n=75), or GEM alone (n=35). Safety was assessed on frequency and incidence of adverse events (AEs). Overall survival (OS), progression-free survival (PFS) and overall response rate (ORR) were collected.

Results:

IMM-101 was well tolerated with a similar rate of AE and serious adverse event reporting in both groups after allowance for exposure. Median OS in the intent-to-treat population was 6.7 months for IMM-101+GEM v 5.6 months for GEM; while not significant, the hazard ratio (HR) numerically favoured IMM-101+GEM (HR, 0.68 (95% CI, 0.44–1.04, P=0.074). In a pre-defined metastatic subgroup (84%), OS was significantly improved from 4.4 to 7.0 months in favour of IMM-101+GEM (HR, 0.54, 95% CI 0.33–0.87, P=0.01).

Conclusions:

IMM-101 with GEM was as safe and well tolerated as GEM alone, and there was a suggestion of a beneficial effect on survival in patients with metastatic disease. This warrants further evaluation in an adequately powered confirmatory study.     

Cholesterol interferes with the MTT assay in human epithelial-like (A549) and endothelial (HLMVE and HCAE) cells

Metabolically active cells are able to convert the MTT [3-(4,5-dimethythiazol-2-yl)-2,5-diphenyltetrazolium bromide] dye to blue formazan. This is the basis of the MTT assay, which is among the most widely used screening methods to evaluate cell viability and proliferation. When testing the effects of cholesterol products on the viability of human pulmonary epithelial-like A549 cells using trypan blue staining (cell numbers) and the MTT assay, results were inconsistent. The MTT assay indicated greater than 50% loss of viability with exposure of cells to cholesterol, whereas there was no decrease in viability indicated by trypan blue exclusion and propidium iodide uptake. A similar decrease in MTT reduction was obtained upon cholesterol treatment in human lung microvascular endothelial cells (HLMVECs) and human coronary artery endothelial cells (HCAECs) without loss of viability. This suggested a direct interference of cholesterol with the assay. However, using a cell-free system, there was no decrease in the reduction of MTT by ascorbic acid during incubation with a similar concentration of cholesterol. Light microscopy revealed enhanced exocytosis of formazan granules in presence of cholesterol. Incubation with apolipoprotein A-1 decreased cholesterol-mediated inhibition of MTT assay. These studies indicate decreased MTT reduction as a result of enhanced exocytosis of formazan due to cholesterol. A careful validation of viability assay procedures is therefore suggested in experiments where cholesterol is a constituent, to avoid a potential bias in concluding results of cytotoxicity studies.     

Management of nonpsychiatric medical conditions presenting with psychiatric manifestations

There is a significant dilemma when underlying medical disorders present as psychiatric conditions. It is important to identify the medical condition because treatment and management strategies need to be directed to the presenting symptoms and also to the underlying medical condition for successful treatment of the patient. Some systemic disorders present with psychiatric manifestations more often than others. The pattern of psychiatric disturbance seen may be specific for a particular medical disorder but may also be varied. Many drug formulations and medications also may produce psychiatric presentations. This article considers the management of nonpsychiatric medical conditions presenting with psychiatric manifestations.     

Role of multidetector computed tomography in assessment of fibro-osseous lesions of the craniofacial complex

Aim

To assess the role of multidetector CT in assessment of fibro-osseous lesions of the craniofacial complex.

Materials and methods

This study included 25 patients. Their age ranged from 15 to 64 years with a mean age of 37.56 ± 15.17 years. All the studied individuals were chosen selectively regarding complaint (those with known fibro-osseous lesions, facial disfigurement, and facial swelling) regardless of age and gender and examined using MDCT in detection of the lesion, and assessment of the extensions.

Results

In the present study, the cranio-facial fibrous dysplasia represented almost half of the presented cases (48%) followed by osteomas (36%) then ossifying fibroma (12%) and brown tumor (4%). 13 out of 25 cases in this study were pathologically proven to be fibro-osseous lesions and surgically operated. The final diagnosis was made by consensus of imaging, clinical findings and pathological features.

Conclusions

Multi-detector row CT images, including reformations, better delineate craniofacial complex anatomy than do single-detector row CT images. Using multi-slice CT scanning in the craniofacial complex becomes possible to depict the complete path of complex structures.     

Using the British National Formulary: best practice for nurse prescribers

This article explains how the British National Formulary (BNF) should be used to facilitate safe, effective and appropriate prescribing. It also outlines, by use of examples, how to find significant changes in a new edition of the BNF so that nurses can remain up to date with the latest prescribing information.