Predictors of cancer mortality in elderly subjects

Cancer mortality was analysed in 3282 elderly subjects aged 65 years from 2 cohorts of general population having different life-style patterns. They took part in the CASTEL (CArdiovascular STudy in the ELderly), a 12-year lasting prospective Italian study. The aim of the present analysis was to identify the items able to influence cancer mortality. A biochemical profile and a questionnaire on lifestyle were collected. Continuous items were averaged and compared with analysis of variance, frequencies with the Pearson's ² test. Mortality was recorded yearly for 12 years from the Registrar's Office and causes of death double-checked by consulting medical case sheets and family doctors' files. The influence of items on mortality was evaluated with the Cox multivariate analysis. Relative risk (RR) of each item was adjusted for confounders. Age, gender, tobacco smoking, the presence of respiratory symptoms, low body mass index in males, serum alanine transaminase (ALT) and alkaline phosphatase (ALP), as well as the town of residence, were powerful predictors of cancer mortality. In the entire population, 12-year overall mortality was 49.4%, cardiovascular 22.8%, and neoplastic 11%; the latter was higher in males than in females (15.7% vs. 7.9%, p < 0.00001). In subjects with respiratory symptoms neoplastic mortality was 11.6% (RR: 1.47) vs. 9.7% in those without symptoms (p < 0.01). Subjects with very low cholesterol ( 178 mg/dl), those with high uric acid ( 8.7 mg/dl) and males with low body mass index ( 22.7 kg/m²) has an increased risk of cancer mortality. RR of cancer mortality increased with increasing ALT or ALP. It was 1 in those having ALT and ALP between 9 and 41.2U/I, 1.41 in those exceeding this latter level and < 1 in those below 9U/I. RR of ALP had a similar trend, the best protective cut-off value being <106 and the worst one > 177U/I. When both serum enzymes were simultaneously raised, RR of cancer mortality increased to 2.84.     

MDA in plasma as a biomarker of exposure to pyrolysed MDI-based polyurethane: correlations with estimated cumulative dose and genotype for N-acetylation

The object of this study was to investigate whether exposure of pipe-layers to thermal degradation products of diphenylmethane diisocyanate (MDI) could be assessed by analysing 4,4-methylenedianiline (MDA) in hydrolysed plasma and urine, and whether the genotype for N-acetylation affected these biomarker levels. Blood and urine samples were drawn from 30-pipe-layers who had been welding polyurethane (PUR) insulated pipes during the preceding 3 months. MDA in hydrolysed plasma and urine was determined with a gas chromatography-mass spectrometry technique, and genotype for N-acetylation was analysed with a polymerase chain reaction technique. MDA in plasma was detected in 18 of the 30 pipe-layers. Their plasma concentrations of MDA varied from 0.05 to 8.48 g/1. There was a significant negative correlation between time since last welding of PUR-insulated pipes and P-MDA (r _s = 0.50, P = 0.005). There was also a significant positive correlation between the estimated number of welded PUR-insulated pipes during the preceding 3 months and P-MDA (r _s = 0.68, P = < 0.001). No significant association between genotype of N-acetylation and P-MDA was observed in a multiple regression analysis when adjustment was made for the estimated cumulative exposure to thermal degradation products of MDI. MDA in urine was detected in only four of the 30 pipe-layers. These four subjects had been welding PUR pipes on the same day as the sampling, or on the day before. The present results indicate the spot plasma samples analysed for MDA may give a rather good estimate of exposure to MDI during the preceding months. P-MDA, but not U-MDA, therefore seems to be a useful biomarker of long-term exposure to MDI. The individual N-acetylation capacity did not affect the plasma levels of MDA.     

Integrating the molecular and the population approaches to dementia research to help guide the future development of appropriate therapeutics

Dementia research over the last 50 years has expanded enormously and has greater international interest now than at any time in history. A variety of scientific approaches have been brought to bear on this complex disorder in which the syndrome of clinical features is its defining importance in societal terms. Little has emerged in terms of tangible benefits for people with dementia to date other than a hugely increased awareness at societal and governmental levels. One of the drivers for the increase in focus has been epidemiological evidence, which has provided background numbers for the justification of resources for dementia research. However it can be argued that this justification did not take into account the true meaning of the population evidence, drawing instead on preconceptions which were, at the time, the widely accepted interpretations of earlier evidence. Current evidence, along with the lack of single therapeutic successes, suggests that a clearer analysis is required which not only examines the value and applicability of existing knowledge, most particularly its generation and generalizability, but also where future investment should go for most likely benefit of populations. This includes a hard look at the pre-occupation of societies with single therapies, their place in the context of prevention more generally, particularly within aging populations, and how evidence is generated on likely impacts and their timeframes.     

Reducing post-lumbar puncture headaches with small bore atraumatic needles

Lumbar puncture for testing of Alzheimer’s disease pathophysiology for diagnostic confirmation is likely to become more common in the coming years. Minimizing adverse effects from this testing will be essential for clinical practice. Small bore, atraumatic needles reduce the occurrence of post-lumbar puncture headache (PLPH). Our goal was to extend this recommendation specifically to a well-characterized aging population. We assessed PLPH in the Alzheimer’s Disease Neuroimaging Initiative cohort and found that PLPH occurrence was reduced only when using a 24 gauge atraumatic needle. We recommend that lumbar punctures for clinical and research purposes in Alzheimer’s disease be conducted with 24 gauge atraumatic needles.     

Combined biomarkers evaluation for diagnosing kidney injury in preeclampsia

Objective: To identify novel potential biomarkers and evaluate combined biomarkers for diagnosing kidney injury with considerable accuracy in preeclampsia. Methods: The level of serum and urine neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), retinol-binding protein (RBP) and interleukin-18 (IL-18) were measured by enzyme-linked immunosorbent assay. Results: The level of serum cystatin C, urine RBP, urine NGAL and urine KIM-1 in preeclampsia group were higher than that in the normal pregnancy group. When four biomarkers are combined, the sensitivity and specificity are 100%/98.20%. Conclusion: Urine KIM-1 is the most potential biomarker for renal injury in preeclampsia. The more biomarkers combined, the more sensitivity and specificity were increased.     

Biomarkers associated with disease severity in allergic and nonallergic asthma

Asthma is a complex, chronic respiratory disease with a wide clinical spectrum. Use of high-throughput technologies has generated a great deal of data that require validation. In this work the objective was to validate molecular biomarkers related to asthmatic disease types in peripheral blood samples and define their relationship with disease severity. With this purpose, ninety-four previously described genes were analyzed by qRT-PCR in 30 healthy control (HC) subjects, 30 patients with nonallergic asthma (NA), 30 with allergic asthma (AA), and 14 patients with allergy (rhinitis) but without asthma (AR). RNA was extracted from peripheral blood mononuclear cells (PBMCs) using the TRIzol method. After data normalization, principal component analysis (PCA) was performed, and multiple approaches were used to test for differential gene expression. Relevance was defined by RQ (relative quantification) and corrected P value (<0.05). Protein levels of IL-8 and MSR1 were determined by ELISA and Western blot, respectively.PCA showed 4 gene expression clusters that correlated with the 4 clinical phenotypes. Analysis of differential gene expression between clinical groups and HCs revealed 26 statistically relevant genes in NA and 69 in AA. Protein interaction analysis revealed IL-8 to be a central protein. Average levels of IL-8 were higher in the asthma patients’ sera (NA: 452.28 ± 357.72, AA: 327.46 ± 377 pg/ml) than in HCs (286.09 ± 179.10), but without reaching statistical significance. Nine genes, especially MSR1, were strongly associated with severe NA.In conclusion, several molecular biomarkers of asthma have been defined, some of which could be useful for the diagnosis or prognosis of disease severity.