The cyclin D1 high and cyclin E high subgroups of breast cancer: separate pathways in tumorogenesis based on pattern of genetic aberrations and inactivation of the pRb node

In an attempt to identify subtypes of breast cancer and pinpoint patterns of cell cycle regulatory defects associated with clinical behaviour, proliferation and other transformation associated events, a multitude of cell cycle regulatory proteins were analysed in a material of 113 primary breast cancers. Increased proliferation was observed in two different scenarios; (1) with high cyclin D1 and elevated retinoblastoma protein (pRb) phosphorylation, (cyclin D1(high) tumours) or (2) with high cyclin E protein but low cyclin D1 and lack of corresponding pRb phosphorylation (cyclin E(high) tumours) indicative of an interrupted pRb pathway. Characteristic for cyclin E(high) tumours were further defects in p53, p27 and bcl-2, while c-erbB2 overexpression and c-myc amplification was found in both cyclin D1(high) and E(high) tumours. Using transfected cell lines overexpressing cyclin E, cyclin E(high) and D1(high) tumours were mimicked and the cyclin D1(high) cell line normalized the cyclin E kinase activity by an induction and redirection of p21 and p27 to the cyclin E complex whereas cyclin E(high) cell lines obtained increased kinase activity without redirection of inhibitors. Based on differences in genetic aberrations as well as function of the pRb node we therefore propose a model in which cyclin D1(high) and cyclin E(high) tumours represent two alternative mechanisms to inactivate the pRb pathway and thereby achieve unrestrained growth in the tumorogenesis of breast cancer.     

Hepatotoxicity of therapeutic short-course paracetamol in hospital inpatients: impact of ageing and frailty

Background: Paracetamol, a commonly used simple analgesic, can be fatal in overdose. Case reports suggest liver damage may occur at therapeutic doses. In older and particularly frail patients, dose reduction of therapeutic paracetamol is recommended due to concerns of an increased risk of hepatotoxicity. Aims: This study aimed to investigate the effects of ageing and frailty on the safety of paracetamol in hospital inpatients commenced on short courses of the drug. Methods: An observational cohort study of young (18–55 years, n = 19), older (≥70 years) fit (n = 24) and older frail (n = 28) hospital inpatients. Treatment group participants commenced regular paracetamol (3–4 g/day) during their hospital admission, whereas the control group was not exposed to paracetamol. In both groups, plasma alanine aminotransferase (ALT) was measured at baseline and day 5, and risk factors for raised ALT were recorded. A random serum paracetamol concentration was measured at day 5 in the treatment group. Results: No older frail treatment participants had an abnormal day 5 ALT. Odds ratios for having a day 5 ALT above the upper limit of normal (ULN) with paracetamol use, compared with unexposed controls, were 3·7 [95% confidence intervals (CI): 0·32, 41·59] for older not frail participants and 2·5 (95% CI: 0·34, 18·3) for younger participants. Decreasing frailty score independently predicted a day 5 ALT above the ULN (P < 0·05). Day 5 serum paracetamol concentrations were highest in older frail participants (P < 0·005). Conclusion: Higher paracetamol concentrations observed in frail older patients after 5 days of therapeutic paracetamol do not necessarily indicate an increased risk of hepatotoxicity.     

Comparison of the effect of post-instruction multiple-choice and short-answer tests on delayed retention learning

Background

People forget much of what they learn, therefore students could benefit from learning strategies that yield long-lasting knowledge. Yet surprisingly, little is known about how longterm retention is most efficiently mastered. We studied the value of teacher made in class tests as learning aids and compared two types of teacher-made tests (multiple choice and short-answer tests) with a no test (control) to determine their value as aids to retention learning.

Method

The study was conducted on two separate batches of medical undergraduate students. This study compared two types of tests [multiple choice questions (MCQs) and short answer questions (SAQs)] with a no test (control) group. The investigation involved initial testing at the end of the lecture (post instruction), followed by an unannounced delayed retention test on the same material three weeks later. The unannounced delayed test comprising of MCQs and SAQs on the same material was given three weeks later to all the three groups.

Results

In batch I, the MCQ group had a higher mean delayed retention score of 10.97, followed by the SAQ group (8.42) and the control group (6.71). Analysis of variance (ANOVA) test and least significance difference (LSD) post hoc test revealed statistically significant difference between the means of the three groups. Similar results were obtained for batch II

Conclusion

Classroom testing has a positive effect on retention learning; both short-answer and multiple-choice tests being more effective than no test in promoting delayed retention learning, however, multiple-choice tests are better.