Mutations in the DNA-binding codons of TP53, which are associated with decreased expression of TRAILreceptor-2, predict for poor survival in diffuse large B-cell lymphoma

Mutations of the TP53 tumor suppressor gene have been associated with poor survival in some series of diffuse large B-cell lymphoma (DLBCL) but not in other studies. The purpose of this study was to identify the frequency of TP53 alterations (mutations or deletions), characterize the gene expression of mutant/deleted cases, and determine the effects of mutations on survival. In a series of DLBCL that had previous gene expression profiling, we identified 24 mutations in 113 cases (21%). There was no difference in the frequency of mutations in the molecular subgroups of DLBCL. Twelve (50%) of the 24 cases had mutations localized to the DNA-binding codons in the core domain of TP53. The presence of any TP53 mutation correlated with poor overall survival (OS; P = .044), but DNA-binding mutations were the most significant predictor of poor OS (P < .001). Multivariate analysis confirmed that the International Prognostic Index, tumor size, and TP53 DNA-binding mutations were independent predictors of OS. Gene expression analysis showed that TRAILreceptor-2 (DR5) was the most differentially underexpressed gene in the TP53 mutated cases. Investigation is warranted into targeted therapy toward TRAIL receptor-2, to potentially bypass the adverse effect of mutated TP53 in DLBCL.     

Handgrip strength in English schoolchildren

Aims: The aims of this study were to evaluate patterns of handgrip (HG) strength in relation to gender and age in English schoolchildren and to compare this with existing data and produce reference data for this population. Methods: The HG of 7147 English schoolchildren (3773 boys and 3374 girls) aged 10–15.9 years was measured using a portable Takei handgrip dynamometer (Takei Scientific Instruments Co. Ltd, Tokyo, Japan). Centile data were produced using the Generalized Additive Models for Location, Scale and Shape. Z‐scores were generated using existing data for European children. Age and gender interactions were analysed using analysis of covariance. Results: In boys and girls, significant increases in HG were found between every age‐group (p < 0.001). Boys were significantly stronger than girls at every age (p < 0.001) and the boys’ age‐related increase was significantly greater than the girls’ (p < 0.001). Conclusion: This study provides reference data for handgrip strength in English schoolchildren. Handgrip strength in English children is broadly similar to existing European data, after adjusting for mass and stature. These data could be used for clinical or athletic screening of low and high strength in this population.     

Effect of quinolone antibiotics on hepatic growth and protein synthesis following partial hepatectomy in rats

Quinolone antibiotics inhibit eukaryotic as well as prokaryotic cell growth and protein synthesis. To determine whether these properties adversely affect hepatic growth and recovery following surgical resection, five groups of healthy, adult male rats (n = 7–8/group) were treated for 10 days with equal volumes of either ofloxacin (50 mg/kg), fleroxacin (25mg/kg), ciprofloxacin (25 mg/kg), norfloxacin (15mg/kg) or sterile saline (controls) prior to 70% partial hepatectomy (PH) and daily thereafter until death. Restituted liver mass, DNA and protein synthesis rates were determined at 24, 48 and 72 h PH. The results of the study revealed that all parameters of hepatic regeneration were similar in the five study groups at each time interval. To ensure that an effect on hepatic regeneration was not dose-dependent, additional experiments were performed where 1, 10 and 100 mg/kg ciprofloxacin was administered and DNA synthesis was measured 24 h post-PH. Once again, the results were similar to sterile saline-treated controls. These findings suggest that the quinolone antibiotics are unlikely to have an adverse effect on hepatic recovery following surgical resection of the liver and are safe to use in that setting.     

Myocardial perfusion is preserved in patients with psoriasis without clinically evident cardiovascular disease

Background  Psoriasis is associated with a premature atherosclerosis due to the chronic inflammatory process. To evaluate the effect of disease process on myocardial perfusion, we planned to perform 99mTc-MIBI myocardial perfusion single photon emission computed tomography (SPECT) in patients with psoriasis.
Methods  The study group consisted of 28 psoriasis patients (17 men, 11 women), aged 18-76 years, and mean age 41.2 ± 14.1 years. The patients were selected among those who were older than 18 years and longer than 10 years of disease duration with more than two times of systemic treatment. All patients underwent 99mTc-MIBI myocardial perfusion SPECT with the same day protocol.
Results  We detected various risk factors including smoking habits in 7, family history of cardiovascular disease in 4, hypertension in 1, hyperlipidemia in 9 patients. We completed myocardial perfusion SPECT for each patient and found normal perfusion pattern in SPECT images.
Conclusion  We detected that myocardial perfusion is preserved in the patients with psoriasis. The majority of acute heart attacks are caused by noncritical coronary stenosis and this may be an explanation for increased cardiovascular risk in these patients despite normal coronary perfusion.