Epidermal growth factor receptors and prognosis in primary breast cancer

A retrospective study was performed on 109 human breast tumors stored in liquid nitrogen in order to assess the prognostic value of epidermal growth factor receptor (EGF-R) (median patient follow-up 5 years). A significant inverse relationship was observed between EGF-R and both estrogen (ER) and progesterone receptors (PR). Univariate analysis showed a trend towards a shorter metastasis-free survival both in the overall population and in node-negative patients with EGF-R positive tumors. Multivariate analysis of the overall population showed that lymph-node involvement and PR status were the only significant variables in predicting metastasis-free survival. However, in patients receiving no adjuvant treatment (hormone therapy or chemotherapy), EGF was the only significant variable in the multivariate Cox analysis. No c-erbB-1 amplification was detected in these tumors.     

Bronchopulmonary cancers: medical approach of the last weeks of life. Study of 191 patients

The characteristics of patients with carcinoma of the lung during their last weeks of life were reviewed in 191 patients treated in the same department and who died between September 1982 and January 1985. The main symptoms were breathlessness (112/191) which posed difficult therapeutic problems preventing domiciliary treatment, and pain (87/191) which was more easily managed in the author's experience. The modes of death were also analysed, showing a number of sudden deaths (14). Therapeutic sedatives were the immediate cause of death in 32 cases, in the first part of the study. The authors make a rapid review of the different available palliative measures. This type of study is the only way of changing medical practices and strategies in patients dying in hospital.     

Biomarkers for Alzheimer's disease therapeutic trials

The development of disease-modifying treatments for Alzheimer's disease requires innovative trials with large numbers of subjects and long observation periods. The use of blood, cerebrospinal fluid or neuroimaging biomarkers is critical for the demonstration of disease-modifying therapy effects on the brain. Suitable biomarkers are those which reflect the progression of AD related molecular mechanisms and neuropathology, including amyloidogenic processing and aggregation, hyperphosphorylation, accumulation of tau and neurofibrillary tangles, progressive functional, metabolic and structural decline, leading to neurodegeneration, loss of brain tissue and cognitive symptoms. Biomarkers should be used throughout clinical trial phases I-III of AD drug development. They can be used to enhance inclusion and exclusion criteria, or as baseline predictors to increase the statistical power of trials. Validated and qualified biomarkers may be used as outcome measures to detect treatment effects in pivotal clinical trials. Finally, biomarkers can be used to identify adverse effects. Questions regarding which biomarkers should be used in clinical trials, and how, are currently far from resolved. The Oxford Task Force continues and expands the work of our previous international expert task forces on disease-modifying trials and on endpoints for Alzheimer's disease clinical trials. The aim of this initiative was to bring together a selected number of key international opinion leaders and experts from academia, regulatory agencies and industry to condense the current knowledge and state of the art regarding the best use of biological markers in Alzheimer's disease therapy trials and to propose practical recommendations for the planning of future AD trials.     

Sodium valproate does not augment Prpsc in murine neuroblastoma cells

Sodium valproate (VPA) has been reported to increase the accumulation of the pathologic isoform of prion protein (PrPsc) in scrapie-infected murine neuroblastoma cells. In this study, the effect of VPA on PrPsc accumulation was investigated in murine N2a neuroblastoma cells chronically infected with scrapie strain 22L (N2a-22L). No accumulation of PrPsc was detected after short-term (3 days) or long-term (21 days) treatment of N2a-22L cells with 4.8, 12, 18 or 24 microM VPA. Higher VPA concentrations (240 and 600 microM) also failed to augment PrPsc expression. In conclusion, in our experimental conditions, no deleterious effect was induced by VPA on prions replication.     

Creating a transatlantic research enterprise for preventing Alzheimer's disease

In recognition of the global problem posed by Alzheimer's disease and other dementias, an international think-tank meeting was convened by Biocat, the Pasqual Maragall Foundation, and the Lou Ruvo Brain Institute in February 2009. The meeting initiated the planning of a European Union-North American collaborative research enterprise to expedite the delay and ultimate prevention of dementing disorders. The key aim is to build parallel and complementary research infrastructure that will support international standardization and inter-operability among researchers in both continents. The meeting identified major challenges, opportunities for research resources and support, integration with ongoing efforts, and identification of key domains to influence the design and administration of the enterprise.     

Health and nutritional promotion program for patients with dementia (nutrialz study): Design and baseline data

Background  There is a lack of data on global weight loss prevention programs for patients with dementia or clear evidence about their impact on a functional level, caregiver burden or the use of healthcare and social resources. “NutriAlz” is a socio-educative and nutritional intervention program to prevent weight loss and loss of function in dementia patients. Study Design and Methods  A cluster randomized multi-centre study, which will allow the comparison of a group benefiting from the intervention with a control group after a year of monitoring. Patients were recruited from 11 hospitals in the ambulatory diagnostic units and day care centres. The baseline interview include: sociodemographic and socioeconomic variables (age, gender, educational level, marital status); diagnostic, treatments, MMS, a list of comorbid conditions; activities of daily living (ADL, IADL), Zarit Scale, brief-NPI, Cornell scale and nutritional status as measured by the Mini Nutritional Assessment. All participants or their family signed the inform consent form. Baseline characteristics  Total of 946 patients were included, with a mean (± SD) of 79 ± 7.3 year of age; 68,1 % were women; 44,9% lives with their partner, only 3% lives alone; 79.8% had Alzheimer’s dementia, 5.25 ± 3.0 years since symptoms of dementia and 2.8 ± 2.11 years since diagnosis. Mean MMSE score was 15.4 ± 6.2; mean weight was 64.4 ± 12.5 kg; mean BMI was 27.0 ± 4.5 (with 3% below 19, 5% between 19–21, 10% between 21–23, and 82% above 23). Mean ADL without difficulties was 3.2± 2.1; mean IADL without difficulties was 0.7± 1.6; mean number of symptoms in the NPI was 4.4 ± 2.59, with severity score of 7.9 ± 5.9 and distress score of 11.3 ± 9.0; mean Zarit scale was 27.4 ± 15.5; mean MNA was 23.2 ± 3.5 with 5 % as malnourished, 32 % at risk of malnutrition, and 63 % with adequate nutritional status.     

Biomarkers of mitochondrial dysfunction and inflammaging in older adults and blood pressure variability

GeroScience - Most physiopathological mechanisms underlying blood pressure variability (BPV) are implicated in aging. Vascular aging is associated with chronic low-grade inflammation occurring in...     

Early results of exclusive radiotherapy in advanced stage cervical carcinoma performed with reference to ICRU Report 38.

BACKGROUND AND PURPOSE: Most of the studies in which medium dose rate (MDR) or high dose rate (HDR) brachytherapy have been used for the treatment of cervical carcinoma were prescribed according to the Manchester system. This study aims to present early results of exclusive radiotherapy, which includes MDR brachytherapy, performed using ICRU 38 recommendations to their full extent. MATERIALS AND METHODS: Between 1994 and 1997, 80 patients with advanced stage (FIGO stages IIA-IVA) cervical carcinoma received external beam therapy (EBT) to the pelvis at a total dose of 46 to 50 Gy and two fractions of MDR (approximately 11.5 Gy/h) brachytherapy delivered to the 60 Gy reference isodose. A dose correction factor of 0.80 was used for dose rate effect. Additionally, 10-14 Gy EBT was given as a parametrial boost. Mean follow-up duration was 25.7 months. RESULTS: Local control (LC) and 3-year overall survival were 63% and 68%, respectively, for all patients. For stages II, III, and IV, LC was 75%, 44%, and 60% and 3-year survival was 75%, 62%, and 50%, respectively. Seven patients had severe late complications (8.7%). CONCLUSIONS: The results of this study encourage the use of ICRU 38 recommendations with MDR or HDR brachytherapy with some additional measures in terms of the radiobiological aspect.