Measuring total health inequality: adding individual variation to group-level differences

Background  

Studies have revealed large variations in average health status across social, economic, and other groups. No study exists on the distribution of the risk of ill-health across individuals, either within groups or across all people in a society, and as such a crucial piece of total health inequality has been overlooked. Some of the reason for this neglect has been that the risk of death, which forms the basis for most measures, is impossible to observe directly and difficult to estimate.     

Control of uremic neuropathy by equilibrium peritoneal dialysis

Motor nerve conduction velocity (MNCV), sensory nerve conduction velocity (SNVC) and distal motor latencies times (DMLT) were evaluated both in upper and lower limbs in three groups of 15 patients of comparable age, treated respectively by extracorporeal dialysis (HD), continuous ambulatory peritoneal dialysis (CAPD) and combined peritoneal dialysis (CPD) for comparable sufficiently long periods. Moreover, MNCV was monitored longitudinally in two groups of patients shifted from CAPD to HD and vice versa. The results show a significant superiority of peritoneal dialysis and particularly of CAPD with respect to HD in controlling uremic neuropathy.     

Effect of two-hour daily hemodialysis and sham dialysis on breath isoprene exhalation

BACKGROUND: Isoprene, a volatile hydrocarbon produced by the human organism, is currently being extensively investigated because the mechanisms underlying its endogenous origin are unknown and because experiments suggest it is toxic and cancerogenous. Previous reports of increases in breath isoprene concentrations during 4-hour, thrice-weekly hemodialysis, but not during continuous ambulatorial peritoneal dialysis, prompted us to assess the behavior of isoprene in another dialytic modality, i.e., short daily hemodialysis (short DHD). Furthermore, in order to determine whether removal of solutes and/or contact of blood with the dialytic membrane influenced the metabolism of isoprene, we performed a sham short hemodialysis session in a subgroup of 8 patients (sham short HD), i.e., with blood flowing through a dialyzer but without dialysate and ultrafiltration. METHODS: The present study evaluates the effects of a two-hour short DHD and a two-hour session of sham HD on isoprene breath levels, as determined by gas chromatography before, during and after sessions. Parallel analyses of ambient air and monitoring of blood pressure and heart rate were performed. RESULTS: Both short DHD and sham DHD induced an increase in breath isoprene exhalation in all patients without being associated with significant hemodynamic variations. CONCLUSION: These findings suggest that the increase in breath isoprene after a session of hemodialysis is neither a reaction to mevalonate depletion nor to metabolic variations induced by the depurative effect, because these changes do not occur during sham HD. It is not related to hemodynamic changes because none were observed in this experimental model. The isoprene increase seems to be of metabolic origin and appears to be connected in some way with the extracorporeal circuit. These interesting findings provide a further impulse to study the biosynthetic pathways involved and to investigate the medical and biological significance of isoprene in humans.     

Overexpression of erythrocyte glutathione S-transferase in uremia and dialysis.

BACKGROUND: Overexpression of glutathione S-transferase (GST; EC 2.5. 1.18) has been documented in the erythrocytes of patients with chronic renal failure, and this event may well be of relevance from a clinical standpoint. In fact, it could serve as a marker of uremic toxicity overall, which can contribute to impair the function and survival of the erythrocytes. However, the biochemical details of this phenomenon are poorly understood. METHODS: In this study, we characterized the expression of GST in erythrocytes of 118 uremic patients under different clinical conditions. The mechanisms responsible for the regulation of protein expression and enzyme activity were investigated in light of different dialysis approaches, oxidative stress, uremic toxins, erythrocyte age, and erythropoietin (EPO) supplementation. RESULTS: Mean GST activity in uremic patients was highly overexpressed with respect to controls, and this phenomenon was exclusively attributable to an increased expression of GST. Overexpression of GST did not appear to be dependent on oxidative stress and was not influenced by vitamin E supplementation. In the same manner, both erythrocyte age and EPO supplementation apparently did not interfere with the GST concentrations, which were the same in controls and patients. Preliminary experiments suggested that high-molecular weight or protein-bound toxins could play some role in the overexpression of GST. CONCLUSIONS: GST expression may be a useful marker for the individual accumulation of uremic toxins as well as of the efficiency of new dialysis strategies in removing them.     

Biological effects of oxidant stress in haemodialysis: the possible roles of vitamin E.

Oxidative stress has been proposed to play a role in many disease states, including cardiovascular and infectious diseases, cancer, diabetes and neurodegenerative pathologies. The fact that these diseases have an increased incidence in uremia, and particularly in dialysis patients, suggests an increased exposure to oxidative stress in this condition. In haemodialysis (HD), the absence of a complete correction of the uremic toxicity together with the untoward effects of the dialysis, malnutrition and the progressive worsening of the clinical condition, can lead to a high susceptibility to oxidative stress by an abnormal production of oxidants - including reactive oxygen species (ROS) and uremic toxins with prooxidant function - and defective antioxidant protection. One of the most investigated biological effects of the oxidative stress in the HD patients is lipid peroxidation in plasma and blood cell membranes. Moreover, we have recently described how abnormal apoptosis in peripheral blood leukocytes is associated with cell oxidative stress (intracellular thiol depletion). Vitamin E, in both in vitro and in vivo conditions, has been proposed to partially correct these effects. In this review we evaluated some features of two new dialysis strategies using an antioxidant approach to the protection against the oxidant stress in HD. Their rationale is based on the emerging role of vitamin E in counteracting some biological effects associated with oxidant stress namely lipid peroxidation and apoptosis. These techniques use: 1) the recirculation of the dialysate through a suspension of vitamin E-enriched liposomes combined with the supplementation by the dialysate with ascorbic acid, this method has been called hemolipodialysis; 2) the coating of the dialysis membrane with vitamin E (vitamin E- modified dialysis membranes). These unconventional approaches to the antioxidant therapy in HD open a widely unexplored and promising field in the evolution of the biomaterials and dialysis quality.     

Microengineered 3D Tumor Models for Anti-Cancer Drug Discovery in Female-Related Cancers

Annals of Biomedical Engineering - The burden of cancer continues to increase in society and negatively impacts the lives of numerous patients. Due to the high cost of current treatment strategies,...     

Prevention of cardiovascular disease in high-risk individuals in low-income and middle-income countries: health effects and costs

In 2005, a global goal of reducing chronic disease death rates by an additional 2% per year was established. Scaling up coverage of evidence-based interventions to prevent cardiovascular disease in high-risk individuals in low-income and middle-income countries could play a major part in reaching this goal. We aimed to estimate the number of deaths that could be averted and the financial cost of scaling up, above current coverage levels, a multidrug regimen for prevention of cardiovascular disease (a statin, aspirin, and two blood-pressure-lowering medicines) in 23 such countries. Identification of individuals was limited to those already accessing health services, and treatment eligibility was based on the presence of existing cardiovascular disease or absolute risk of cardiovascular disease by use of easily measurable risk factors. Over a 10-year period, scaling up this multidrug regimen could avert 17.9 million deaths from cardiovascular disease (95% uncertainty interval 7.4 million-25.7 million). 56% of deaths averted would be in those younger than 70 years, with more deaths averted in women than in men owing to larger absolute numbers of women at older ages. The 10-year financial cost would be US$47 billion ($33 billion-$61 billion) or an average yearly cost per head of $1.08 ($0.75-1.40), ranging from $0.43 to $0.90 across low-income countries and from $0.54 to $2.93 across middle-income countries. This package could effectively meet three-quarters of the proposed global goal with a moderate increase in health expenditure.     

Insights into the molecular requirements for the anti-obesity activity of a series of CB1 ligands

Two-dimensional and 3D quantitative structure-activity relationships studies were performed on a series of diarylpyridines that acts as cannabinoid receptor ligands by means of hologram quantitative structure-activity relationships and comparative molecular field analysis methods. The quantitative structure-activity relationships models were built using a data set of 52 CB1 ligands that can be used as anti-obesity agents. Significant correlation coefficients (hologram quantitative structure-activity relationships: r2 = 0.91, q2 = 0.78; comparative molecular field analysis: r2 = 0.98, q2 = 0.77) were obtained, indicating the potential of these 2D and 3D models for untested compounds. The models were then used to predict the potency of an external test set, and the predicted (calculated) values are in good agreement with the experimental results. The final quantitative structure-activity relationships models, along with the information obtained from 2D contribution maps and 3D contour maps, obtained in this study are useful tools for the design of novel CB1 ligands with improved anti-obesity potency.