TASK DEFINITION: Given a passage, construct a question on the basis of the information present in the passage. Construct the question in such a way that (i) it is unambiguous, (ii) it is answerable from the passage, (iii) its answer is unique (iv) it answer uses text phrases from the passage. Avoid creating questions that (i) can't be answered correctly without actually understanding the passage and (ii) uses the same words or phrases given in the passage.
PROBLEM: Cardiac rupture is a catastrophic complication that occurs after acute myocardial infarction (MI) and, at present, there are no effective pharmacological strategies for preventing this condition. Here we investigated the effect of the angiotensin II receptor blocker olmesartan (Olm) on post-infarct cardiac rupture and its underlying mechanisms of action.', 'C57Bl/6 mice with MI were treated with Olm, aldosterone (Aldo) or vehicle. Cultured neonatal cardiomyocytes and fibroblasts were exposed to normoxia or anoxia and treated with angiotensin II (Ang II), RNH6270 (active ingredient of Olm) or Aldo.', 'The mortality rate and incidence of cardiac rupture in MI mice during the first week in the Olm-treated group were significantly lower than in the vehicle-treated group. Olm or RNH6270 reduced myeloperoxidase staining in the infarcted myocardium, decreased apoptosis in cultured cardiomyocytes and fibroblasts, as assessed by Hoechst staining and TUNEL assay, attenuated the accumulation of p53 and phosphorylated p53 and cleaved caspase 3 induced by MI or Ang II, as assessed by Western blotting, and up-regulated growth differentiation factor-15 (GDF-15). In cultured cardiomyocytes and fibroblasts, treatment with Ang II, Aldo or anoxia significantly down-regulated the expression of GDF-15.

SOLUTION: Does olmesartan prevent cardiac rupture in mice with myocardial infarction by modulating growth differentiation factor 15 and p53?

PROBLEM: It has been shown that the circulating Renin-Angiotensin System (RAS) is activated during normal pregnancy, but little is known about RAS in pregnancies complicated by gestational diabetes (GDM). GDM is considered not merely a temporary condition, but a harbinger of hypertension and type 2 diabetes. The aim of this study was to evaluate the circulating RAS profile in normotensive women with GDM at the third trimester of pregnancy and to compare the results with healthy pregnant and non-pregnant age-matched women.', 'The diagnostic criteria for GDM followed the recommendations of the American Diabetes Association. Angiotensin I (Ang I), Angiotensin II (Ang II) and Angiotensin 1-7 [Ang-(1-7)] were determined in 24 pregnant patients with GDM; 12 healthy pregnant women and 12 non-pregnant women by radioimmunoassay.', 'Levels of Ang I, Ang II and Ang-(1-7) were higher in pregnant women (p<0.05), but showed a different pattern in the GDM group, in which reduced Ang-(1-7) circulating levels were found (p<0.05). This observation was confirmed by the significantly lower Ang-(1-7)/Ang I ratio (p<0.05).

SOLUTION: Does the pregnancy-induced increase of plasma angiotensin- ( 1-7 ) is blunt in gestational diabetes?

PROBLEM: Clinical trials of adjuvant radiotherapy after mastectomy have largely excluded women aged 70 years or over, even though they comprise 30% of the breast cancer population. This study examined outcomes in elderly women with high-risk breast cancer treated with or without postmastectomy radiotherapy (PMRT).', 'Data were analysed for 233 women aged 70 years or over with high-risk breast cancer (tumours > 5 cm or > or = 4 positive axillary nodes) treated with mastectomy and referred to the British Columbia Cancer Agency from 1989 to 1997. Tumour and treatment characteristics were compared between two cohorts: women treated with PMRT (n = 147) vs women treated without PMRT (n = 86). Univariate and multivariate analyses of 10-year Kaplan-Meier locoregional recurrence (LRR), distant recurrence, breast cancer-specific survival and overall survival were carried out.', 'Median follow-up time was 5.5 years. The distribution of tumour sizes was similar in the two groups. Compared with women treated without PMRT, higher proportions of women who underwent PMRT had four or more positive nodes (83% vs 67%, P = 0.01) and positive surgical margins (14% vs 4%, P = 0.02). Systemic therapy, used in 94% of women, was comparable in the two cohorts (P = 0.63). Elderly women treated with PMRT had significantly lower LRR compared with women treated without PMRT (16% vs 28%, P = 0.03). No differences in distant recurrence, breast cancer-specific survival or overall survival were observed in the two treatment groups (all P > 0.05). On multivariate analysis, the omission of PMRT and the presence of high-grade histology were significant predictors of LRR, whereas an increasing number of positive nodes was significantly associated with distant recurrence and overall survival.

SOLUTION:
Does postmastectomy radiotherapy reduce locoregional recurrence in elderly women with high-risk breast cancer?