Stroke management: updated recommendations for treatment along the care continuum

The Australian Clinical Guidelines for Stroke Management 2010 represents an update of the Clinical Guidelines for Stroke Rehabilitation and Recovery (2005) and the Clinical Guidelines for Acute Stroke Management (2007). For the first time, they cover the whole spectrum of stroke, from public awareness and prehospital response to stroke unit and stroke management strategies, acute treatment, secondary prevention, rehabilitation and community care. The guidelines also include recommendations on transient ischaemic attack. The most significant changes to previous guideline recommendations include the extension of the stroke thrombolysis window from 3 to 4.5 h and the change from positive to negative recommendations for the use of thigh-length antithrombotic stockings for deep venous thrombosis prevention and the routine use of prolonged positioning for contracture management.     

Hemolytic Disease of the Newborn Apparently Caused by Anti-Lua

Report of the first example of pure anti-Lu^a associated with hemolytic disease of the newborn. Of special interest is the fact that this serum demonstrated a marked prozone reaction in saline, papain and indirect Coombs titrations, and is the first anti-Lu^a serum to react well by the indirect Coombs technic.     

Integrated analytical techniques with high sensitivity for studying brain translocation and potential impairment induced by intranasally instilled copper nanoparticles

Health impacts of inhalation exposure to engineered nanomaterials have attracted increasing attention. In this paper, integrated analytical techniques with high sensitivity were used to study the brain translocation and potential impairment induced by intranasally instilled copper nanoparticles (CuNPs). Mice were exposed to CuNPs in three doses (1, 10, 40 mg/kg bw). The body weight of mice decreased significantly in the 10 and 40 mg/kg group (p < 0.05) but recovered slightly within exposure duration. Inductively coupled plasma mass spectrometry (ICP-MS) analysis showed that CuNPs could enter the brain. Altered distribution of some important metal elements was observed by synchrotron radiation X-ray fluorescence (SRXRF). H&E staining and immunohistochemical analysis showed that CuNPs produced damages to nerve cells and astrocyte might be the one of the potential targets of CuNPs. The changes of neurotransmitter levels in different brain regions demonstrate that the dysfunction occurred in exposed groups. These data indicated that CuNPs could enter the brain after nasal inhalation and induced damages to the central nervous system (CNS). Integration of effective analytical techniques for systematic investigations is a promising direction to better understand the biological activities of nanomaterials.     

Risk stratification in pre-hospital management of myocardial infarction with ST elevation: value of a risk score profile

The aims of this study were to evaluate new tools of risk stratification in an unselected population of myocardial infarction (MI), usable in a pre-hospital situation, and to compare the risk profile of these patients with those of other clinical trials or myocardial infarction registries. The risk scores of death at 30 days (TIMI score and TIMI risk index) based on data available in the context of coronary emergencies, were applied to the population base of the MI observatory of myocardial infarction in the C?te d'Or (RICO). The risk profile was expressed by the smoothed graph of frequency distribution of each score. The TIMI score applied to the RICO population had a high discriminating power (c = 0.80) for mortality whereas TIMI risk index was less powerful (c = 0.57). The risk profile of the RICO population was comparable to that of InTIME II, ASSENT 2 and the NRMI with reperfusion registry. The NRMI without reperfusion and the MAGIC studies had different profiles characterised by a shift in the graph towards high risk patients. The authors conclude that risk stratification scores, like the TIMI score, are valuable tools for early triage in the management of MI patients. The risk profiles allow comparative analysis of risk levels of populations notably with respect to other registries and also with respect to randomised clinical trials.     

Checkpoint kinase 1 protein expression indicates sensitization to therapy by checkpoint kinase 1 inhibition in non–small cell lung cancer

Background

When presenting with advanced stage disease, lung cancer patients have <5% 5-y survival. The overexpression of checkpoint kinase 1 (CHK1) is associated with poorer outcomes and may contribute to therapy resistance. Targeting CHK1 with small-molecule inhibitors in p53 mutant tumors might improve the effectiveness of chemotherapy and radiotherapy in non–small cell lung cancer (NSCLC).

Methods

We evaluated CHK1 messenger RNA and protein levels in multiple NSCLC cell lines. We assessed cell line sensitization to gemcitabine, pemetrexed, and radiotherapy by CHK1 inhibition with the small molecule AZD7762 using proliferation and clonogenic cell survival assays. We analyzed CHK1 signaling by Western blotting to confirm that AZD7762 inhibits CHK1.

Results

We selected two p53 mutant NSCLC cell lines with either high (H1299) or low (H1993) CHK1 levels for further analysis. We found that AZD7762 sensitized both cell lines to gemcitabine, pemetrexed, and radiotherapy. Chemosensitization levels were greater, however, for the higher CHK1 protein expressing cell line, H1299, when compared with H1993. Furthermore, analysis of the CHK1 signaling pathway showed that H1299 cells have an increased dependence on the CHK1 pathway in response to chemotherapy. There was no increased sensitization to radiation in H1299 versus H1993.

Conclusions

CHK1 inhibition by AZD7762 preferentially sensitizes high CHK1 expressing cells, H1299, to anti-metabolite chemotherapy as compared with low CHK1 expressing H1993 cells. Thus, CHK1 inhibitors may improve the efficacy of standard lung cancer therapies, especially for those subgroups of tumors harboring higher expression levels of CHK1 protein.     

Interobserver variability,detection rate,and lesion patterns of 68Ga-PSMA-11-PET/CT in early-stage biochemical recurrence of prostate cancer after radical prostatectomy

European Journal of Nuclear Medicine and Molecular Imaging - 68Ga-PSMA-11-PET/CT is increasingly used in early-stage biochemical recurrence of prostate cancer to detect potential lesions for an...