Changes in RDW according to prognostic predictors in newly diagnosed multiple myeloma.

RDW is an erythrocyte index that increase in multiple myeloma, in which it appears to have an important role in predicting outcome. For this reason, we performed a retrospective analysis to evaluate the relationships of RDW with some important prognostic predictors. Specifically, in a cohort of 190 newly diagnosed multiple myeloma patients, we have examined the behaviour of RDW and its trend in relation to the ISS stage and other prognostic factors, such as albumin, beta-2 microglobulin, LDH and bone marrow plasma cell infiltration. We performed the analysis in the entire cohort of patients and in the three different disease isotypes (Light chain, IgA, and IgG multiple myeloma). The evaluation of RDW in the different isotypes was made with the Kruskal-Wallis test, integrated by the Dunn test. The comparison between the subgroups allocated above and below the median value of each prognostic factor, was made with the Mann-Whitney test. From our analysis, we observed that RDW is higher in the IgA multiple myeloma, and it increases significantly from ISS I to III. Moreover, RDW increases in the presence of lower albumin values, higher levels of beta2-microglobulin and LDH and in the presence of a greater bone marrow plasma cell infiltrate.

The unpredictable erythrocyte deformability alteration in some hematological disorders: How the classification of primary hyperviscosity syndromes could change.

According to Wells classification, it is possible to distinguish the primary hyperviscosity syndromes in polycythemic, sclerocythemic and sieric and/or plasmatic. In polycythemia vera, multiple myeloma, Waldenström's macroglobulinemia, and monoclonal gammopathy of undetermined significance, we have observed an unexpected behaviour of the erythrocyte deformability. This data highlights that the hemorheological alteration present in polycythemia vera has not been related to the increase of RBC mass only, as well as that present in plasmacellular dyscrasias has not been attributable to the increase of plasma viscosity only.The aim of this paper is to suggest some starting points for an accurate reflection, emphasizing the need of a revision of the current classification of primary hyperviscosity syndromes.

Erythrocyte deformability and hemorheological profile in multiple myeloma.

The hemorheological profile in multiple myeloma (MM) has been extensively studied. Our investigation regarded the behavior of whole-blood viscosity, plasma viscosity and erythrocyte deformability in MM. We enrolled 24 MM patients; 13 of them had been recently diagnosed and were at the initial stage of therapy, 6 were on consolidation/conservation therapy and 5 had achieved a complete remission. On fasting venous blood we evaluated whole-blood and plasma viscosity at high and low shear rates, haematocrit, the ratios between whole-blood viscosity (at high and low shear rate) and haematocrit×100, the ratio between plasma viscosity at low and high shear rate and the erythrocyte deformability examined by using laser diffractometry and expressed as elongation index. A significant increase in plasma viscosity at low shear rate and a marked decrease in haematocrit were observed in MM patients compared with normal controls. Also the ratio between the high shear rate whole-blood viscosity and haematocrit ×100 and the ratio between the low and high shear rate plasma viscosity were significantly increased in MM patients. A significant decrease in erythrocyte deformability, especially at low shear stresses, was found. We discuss some hypotheses that might explain the behavior of red blood cell deformability in MM, considering that its impairment, in addition to the increase of plasma viscosity, can alter the microcirculatory flow in these patients.

Hemorheological parameters in Monoclonal Gammopathy of Undetermined Significance (MGUS).

There is scarcity of information about the hemorheological pattern in subjects with Monoclonal Gammopathy of Undetermined Significance (MGUS). This preliminary research is focused on the behaviour of whole-blood and plasma viscosity, haematocrit and erythrocyte deformability in the above clinical condition. We enrolled 21 MGUS subjects (10 women and 11 men; mean age 66.4 ± 11.6 years). In fasting venous blood we examined whole-blood and plasma viscosity at high and low shear rates, haematocrit, the ratios between whole-blood viscosity (at high and low shear rate) and haematocrit × 100, the ratio between plasma viscosity at low and high shear rate, and the erythrocyte deformability expressed as elongation index. By comparing normal controls to MGUS subjects a significant increase in whole-blood viscosity at high shear rate and in plasma viscosity at low shear rate were observed. In MGUS subjects the ratios between the high and low shear rate blood viscosity and haematocrit × 100, as well as the ratio between the low and high shear rate plasma viscosity were significantly higher. In MGUS subjects a marked decrease in erythrocyte deformability was also observed. The alteration of the hemorheological profile found in these subjects might be involved in the pathogenesis of thromboembolic events, which occur with a high frequency in MGUS.

Behaviour of the neutrophil to lymphocyte ratio in young subjects with acute myocardial infarction.

In the last years the neutrophil to lymphocyte ratio (NLR) has been examined in cardiovascular disorders and in particular in coronary artery disease and acute myocardial infarction (AMI). Now we examined this parameter in subjects with juvenile myocardial infarction at the initial stage and after 3 and 12 months. We enrolled 123 young subjects (112 men and 11 women, mean age 39.4 ± 5.8 yrs) with AMI. The time interval between the AMI onset and the investigation was 13 ± 7 days. The mean value of NLR observed in young AMI subjects was significantly increased compared to normal controls (N = 1.817 ± 0.711; young AMI subjects = 2.376 ± 0.873, p <  0.0001). NLR does not discriminate STEMI (2.427 ± 0.878) and non STEMI (2.392 ± 0.868) or diabetics (2.604 ± 1.000) and non diabetics (2.324 ± 0.853), but it differentiates smokers (2.276 ± 0.853) and non smokers (2.837 ± 1.072). NLR at the initial stage is not correlated with the number of cardiovascular risk factors or with the extent of the coronary disease. In this study we found a significant decrease of neutrophil count at 3 and 12 months later AMI without any significant variation of lymphocyte and consequently we observed a decrease in NLR at these two intervals of time in comparison with the initial stage. Despite some limitations present in this study, it is interesting to underline that also in juvenile myocardial infarction this low-cost haematological marker may be considered together with other inflammatory indicators.

Nitric oxide metabolites (nitrite and nitrate) in several clinical condition.

We determined the concentration of nitric oxide metabolites (NO2-+NO3-), expressed as NOx, in several clinical conditions. Regarding this, we have examined 25 subjects with arterial hypertension, 41 subjects with chronic kidney disease in conservative treatment, 106 subjects with metabolic syndrome subdivided according to the presence (n = 43) or not (n = 63) of diabetes mellitus, 48 subjects with obstructive sleep apnea syndrome (OSAS), 14 women with systemic sclerosis complicated with Raynaud's phenomenon, 42 dialyzed subjects and 105 young subjects with acute myocardial infarction (AMI). In subjects with arterial hypertension, chronic kidney disease, metabolic syndrome, systemic sclerosis, as well as, in dialyzed and AMI subjects, we found at baseline a NOx increase. In dyalized subjects after a standard dialysis session, we observed a decrease in NOx. The increase in NOx in juvenile AMI was significantly influenced by cigarette smoking and less by cardiovascular risk factors and the extent of coronary lesions; at 3 and 12 months later than the initial event, we observed a decrease of NOx that remains significantly higher than the control group. In subjects with OSAS no difference in NOx was noted in comparison with normal controls, although their subdivision according to the apnea/hypopnea index operates a clear distinction regarding NOx concentration.

[The role of lactate besides the lactic acidosis]. / Il ruolo del lattato oltre l'acidosi lattica.

Lactic acidosis (LA) is the most common form of metabolic acidosis defined by values of lactate greater than 5 mmol / l and by a pH <7.34. The pathogenesis of LA involves hypoxic (type A) and non hypoxic (type B) causes which are often coexisting. Lactic acidosis is usual in hospitalized population especially in subjects in intensive care units, in which lactate levels on admission could be predictors of mortality even in the absence of organ dysfunction or shock. The outcome is mainly dependent on the cardiovascular effects of acidosis. In subjects with cardiogenic shock, the increased lactate/pyruvate ratio, detectable at onset, is correladed with mortality. An early assessment of blood and tissue lactate levels could play a role in the therapeutic management as well as in outcome. LA could be a unfavorable prognostic factor in cancer. The lactate would act also as "signal molecule" and as a promoting factor in angiogenesis and tumor progression. In the presence of risk factors for LA the role of metformin may be overrated. Despite the doctrinal progress to understand the pathogenesis and pathophysiology, there is not univocal consensus on the therapeutic treatment of LA. The identification and the attempt to remove the cause of acidosis are main aims; treatment with sodium bicarbonate is a matter of debate as the data on the cardiovascular effects and mortality are unclear. The therapy with carbicarb, dichloroacetate or THAM has shown no specific advantages in terms of mortality. In experimental models of LA and shock the use of sodium-hydrogen exchanger-1 (NHE1) selective inhibitors reduces cell damage and inflammatory cytokines synthesis; it also improves cardiac performance and decreases mortality.

Myocardial infarction in young adults: risk factors, clinical characteristics and prognosis according to our experience.

OBJECTIVES: Myocardial infarction is a relatively unusual phenomenon in young subjects. The aim if this work is to characterize the risk profile and factors influencing outcomes of these patients since it makes possible to manage prevention interventions. PATIENTS AND METHODS: We examined cardiovascular risk factors, clinical presentation, angiographic picture and outcome of a group of young patients hospitalized for a myocardial infarction. We enrolled 121 young patients consecutively admitted to our hospital for a myocardial infarction and examined them not only at the initial stage, but also after 3 months and one year; finally a long-term telephonic follow up was performed, when possible. RESULTS: We found some peculiarity making these patients quite different from the older ones who develop a myocardial infarction: cigarettes smoking, family history of ischemic heart disease and hyperlipidemia were the most frequent cardiovascular risk factors, while diabetes and hypertension were less represented; moreover coronary angiography showed more frequently a less extensive coronary atherosclerosis. Patients who developed a cardiovascular event at follow-up presented a significantly higher prevalence of hypertension and obesity and a significantly lower frequency of healthy coronary arteries and of previous revascularization. CONCLUSIONS: Myocardial infarction in young adults presents several peculiarities, represented not only by the risk profile, but also by the angiographic picture and the prognosis. Considering the long life expectancy of the involved population, the essential role of preventive interventions should be strongly underlined.

[Hyponatremic syndrome]. / Sindrome iponatriemica.

Sodium, the most important extracellular fluid electrolyte, is the focus of several homeostatic mechanisms that regulate fluid and electrolyte balance. Hyponatremia is a common electrolyte abnormality caused by an actual sodium deficiency or extracellular compartment fluid excess. Clinical symptoms are related with acuity and speed with which this abnormality is established. The symptoms are mainly neurological and neuromuscular disorders (headache, confusion, stupor, seizures, coma) due to brain cells edema. Hyponatremia due to sodium deficiency is caused by sodium loss from kidney (nephritis, diuretics, mineralocorticoid deficiency) and / or extrarenal (vomiting, diarrhea, burns). Hyponatremia due to water excess seems to be the most common and it is attributable to cirrhosis, nephrotic syndrome, heart failure, infusion 5% glucose solutions and drugs that stimulate ADH secretion. It was recently highlighted the role of inflammation and IL-6 in the non-osmotic ADH release. Hyponatremia is considered also marker of phlogosis. Acute (<48 h) and severe (<125 mEq/ L) hyponatremia is a medical emergency that requires prompt correction. Patients with chronic hyponatremia have a high risk of osmotic demyelination syndrome if rapid correction of the plasmatic sodium occurs. In combination with conventional therapy, a new class of drugs, vasopressin receptors antagonists (AVP-R antagonists) would be able to increase the excretion of electrolyte-free water and the serum sodium concentration.

Exercise in obesity management.

Obesity is considered a global epidemic by the World Health Organization in both developed and developing countries. It is associated with a higher risk of cardiovascular disease, diabetes mellitus, cancer and other clinical conditions. Visceral fat is the major responsible for metabolic complications, such as insulin-resistance, and it acts as an endocrine organ producing adipokines involved in lipidic and glycaemic metabolism. TNF-α and IL-6, produced by adipose tissue, increase NADPH oxidase activity activating protein kinase C and NFκB leading to an higher oxidative stress. The obesity management includes physical activity: aerobic training improves lipid profile and insulin sensitivity while resistance training increases lean body mass and basal metabolism and has beneficial effects on bone mineral density and glucose tolerance. An exercise program should include 30 to 45 minutes of moderate intensity activity performed 3 to 5 days a week. Weight loss is also associated with lower blood pressure and improved oxidative status, confirmed by reduced oxidative stress markers and increased antioxidant protection. An inverse association between indicators of systemic inflammation and physical activity has been demonstrated, so exercise training may reduce endothelial damage and cardiovascular risk.

Effects of exercise on inflammation markers in type 2 diabetic subjects.

Endothelial dysfunction and plasma markers of inflammation are significantly increased in type 2 diabetics. Several proinflammatory cytokines, acute-phase proteins, and cell adhesion molecules, such as C-reactive protein (CRP), interleukines (IL), and tumor necrosis factor alpha (TNF-α), seem to play a role in the low-grade systemic inflammation observed in these subjects. Lifestyle changes are necessary to prevent atherosclerosis and cardiovascular events. Physical exercise is known to reduce markers of inflammation by decreasing adipocytokine production and cytokine release from skeletal muscles, endothelial cells, and immune system and also improving antioxidant status. In type 2 diabetics, aerobic and resistance training have different effects on cytokine levels, and the differences in the modalities of exercise (type, duration, and intensity) and especially in the examined population could produce different results. Recent research showed that combined exercise has greater anti-inflammatory effects than aerobic or resistance exercise alone causing a deepest decrease in CRP, IL-6, IL-1ß, TNF-α, leptin, and resistin and a higher increase in anti-inflammatory cytokines such as IL-4, IL-10, and adiponectin.

Ventana sin costo a la información biomédica; una perspectiva académica / Free window biomedical information to a academic perspective

Un acceso fácil y sin costo a revistas médicas en INTERNET a través de la Fundación Ginebra de Educación Médica e Investigación, la que facilita a médicos y otros profesionales de la Salud acceso a una biblioteca completa para investigar y revisar artículos, permitiéndoles crear sus propios programas de Educación Médica Contínua

An easy approach to free medical journals in INTERNET through the non profit contribution of the Geneva Foundation for Medical Education and Research, which facilitates doctors and other health related professionals access to a complete library of research and review articles, allowing them to create a self oriented program of Continued Medical Education.

[Metabolic syndrome: from insulin resistance to adipose tissue dysfunction]. / Sindrome metabolica: dall'insulino-resistenza alla disfunzione del tessuto adiposo.

Recently the definition, the pathophysiology and even the clinical utility of metabolic syndrome (MS) have been discussed. The risk induced by each component of the metabolic syndrome is higher than the risk induced by MS alone. MS alone is, in fact, a weaker predictor of cardiovascular disease than diabetes. New criteria to define the metabolic syndrome have been proposed, as adipokines, CRP and PAI-1. IGFBP-1 is related to hyperinsulinemia/insulin resistance and to the risk of diabetes and fatal ischemic heart disease development. IGF/IGFBP system could be a link between insulin resistance and cardiovascular disease. RBP-4 can attenuate insulin signalling in skeletal muscle and induce hepatic gluconeogenesis. The belief that insulin-resistance is the main cause of MS could change in favour of the adipose tissue dysfunction. The most common cause of a reduced capacity of the adipose tissue to store fats is the increased dietary intake, also present in lipodistrophy, type 1 diabetes mellitus and polycystic ovarian syndrome. The adipose tissue production of adipokines and cytokines (such as IL-6, TNF-alpha and TGF-beta) and the excessive lipid flux towards muscles, heart and liver (Ectopic fat storage syndrome) contribute to the MS genesis and to an increased cardiovascular risk. The comprehension of adipose tissue dysfunction mechanisms offers new possibilities of prevention and therapy.

Diagnóstico y tratamiento del loxoscelismo / Diagnostic and treatment of the loxoscelism

El loxoscelismo es una enfermedad de presencia mundial y es causada en Chile por la Loxosceles laeta o araña de los rincones. Entre los componentes enzimáticos del veneno inyectado está la esfingomielinasa D, causante de necrosis y hemólisis, principales características patológicas de la enfermedad. Sus presentaciones clínicas fundamentales son: el loxoscelismo cutáneo (80 por ciento) y el loxoscelismo cutáneo visceral (20 por ciento). El primero es un cuadro local de necrosis dermoepidérmica de extensión variada, que mayoritariamente evoluciona hacia la regresión con medidas conservadoras y que en el 10 por ciento requiere terapia quirúrgica. El cuadro cutáneo visceral es una variante grave, que requiere terapia precoz y agresiva de su componente sistémico, el que por la hemólisis intravascular que lo causa, puede producir daño renal y hepático y de otros parénquimas nobles. Su tratamiento es inespecífico y apunta a disminuir o modular la respuesta inflamatoria y sus efectos. Existe un antisuero cuya eficacia y seguridad de uso en humanos no ha sido aún demostrada y cuya indicación habitual no está difundida ni recomendada. Dada la gravedad que puede revestir este envenenamiento y de que no existen medidas específicas para contrarrestar su efecto, la recomendación principal es evitar el contacto con el agente, la araña Loxosceles laeta, erradicándola activamente del ambiente doméstico.

Chronic renal failure: oxidative stress, endothelial dysfunction and wine.

Atherosclerosis development is accelerated in chronic renal failure (CRF) and is the major cause of death in this clinical condition. An increased oxidative stress and an endothelial dysfunction, with their complex interrelationships, are relevant aspects of atherogenesis in CRF patients and might be targets for treatment. Many studies have underlined the cardiovascular protection provided by a moderate wine consumption. This beneficial effect is due to both alcohol and nonalcoholic components of wine including several phenolic molecules such as quercetin and resveratrol. Wine polyphenols have antioxidant properties and favorably influence endothelial function, in particular by stimulating nitric oxide-mediated vasodilation and inhibiting the endothelin-1 pathway. The possible advantage of a moderate wine consumption in CRF patients can be hypothesized and deserves clinical investigation.