Biomedical subjects
Publications and source records attributed to Massimo Cirillo.
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Cardiovascular disease is a major cause of morbidity and mortality in chronic kidney disease. Radionuclide-based methods can be used for analyses on the perfusion of coronary arteries and ventricular function. The present study reports the use of a new procedure for continuous measurements of left ventricle function during a dialytic session with the use of a recently developed portable gamma radiation detector (ventricular function study system). On average, left ventricle ejection fraction and stroke volume progressively and continuously decreased throughout the session (end session versus baseline: -13.8% for ejection fraction, -25.9% for stroke volume, P<.02). A biphasic response was found for heart rate: a transient modest decrease (at session midpoint, -4.2%) followed by an increase up to values higher than baseline (end session, +4.7%). Cardiac output decreased by 10.4% at session midpoint (P=.023 versus baseline) without further reduction in the following hours. Mean changes in systolic pressure paralleled data for cardiac output. Individual changes in indices of left ventricle function were scattered and strongly were correlated with thickness of interventricular septum and telediastolic left ventricular volume measured by standard echocardiogram in the interdialytic period (R>.75, P<.05). Data indicate that the ventricular function study system could be a powerful tool for characterization of the profile of left ventricular function in hemodialyzed patients.
About 85% of patients on maintenance hemodialysis have sleep disorders that depend on comorbidities, age, morning dialytic shift, and blood pressure. They are ameliorated by erythropoietin, by transplantation, and by daily and nocturnal dialysis. Some data exist on sleep disorders in CKD patients, and show that lack of a refreshing sleep is present even at early stages of the disease and may affect 82.2% of patients without any relationship to comorbidities.
Microalbuminuria is a mild urinary albumin elevation and is associated with cardiovascular disease. Urinary albumin/creatinine ratio is recommended for microalbuminuria assessment, because it reflects urinary albumin excretion. Muscular mass could affect albumin/creatinine ratio, because urinary creatinine reflects muscular mass. The study investigated high albumin/creatinine ratio attributed to low urinary creatinine without microalbuminuria. The Gubbio Population Study for ages 45 to 64 collected data on weight, skinfold, urinary albumin, urinary creatinine, and coronary heart disease. Weight and skinfold thickness were used to calculate fat and nonfat mass and urinary creatinine as a marker of muscular mass. Microalbuminuria was defined as urinary albumin of 20 to 199 microg/min and high albumin/creatinine ratio as a ratio of 17 to 250 microg/mg in men and of 25 to 355 microg/mg in women. Persons with macroalbuminuria (urinary albumin > or =200 microg/min) were excluded to focus analyses on microalbuminuria. Coronary heart disease was defined by ECG and questionnaire. The target cohort consisted of 1623 men and women, ages 45 to 64. Prevalence was 8.5% for high albumin/creatinine ratio (n=138), 4.3% for microalbuminuria (n=69), 5.2% for high albumin/creatinine ratio without microalbuminuria (n=85), and 1.0% for nonhigh albumin/creatinine ratio with microalbuminuria (n=16). High albumin/creatinine ratio without microalbuminuria was inversely associated with nonfat mass and urinary creatinine (P<0.04). Compared with persons with a nonhigh albumin/creatinine ratio, coronary heart disease was more prevalent in persons with a high albumin/creatinine ratio and microalbuminuria (18.9% and 7.1%; P=0.002), not in persons with a high albumin/creatinine ratio without microalbuminuria (8.2% and 7.1%; P=0.706). A high albumin/creatinine ratio in persons with low muscle mass indicates low urinary creatinine more often than microalbuminuria and cardiovascular disease.
UNLABELLED: Introduction The association between type 2 diabetes and hypertension has long been described, but the mechanisms remain unclear. Na-Li countertransport (Na-Li CT) activity is viewed as a marker of inherited pre-disposition to hypertension, especially if associated with other metabolic abnormalities. Aim To evaluate whether enhanced Na-Li CT activity is a predictor of type 2 diabetes. METHODS: Study participants were 2167 men and women, 30-70 years. Na-Li CT activity, glucose, HDL cholesterol, blood pressure, height, and weight were measured. Six years incidence of diabetes (WHO) was assessed. RESULTS: Baseline Na-Li CT activity was significantly higher for people who developed diabetes at follow-up (n = 101) than for those who remained non-diabetic (364 +/- 184 vs 300 +/- 150 micromol/l RBC/h, P < 0.001). This finding was confirmed after correction for obesity, hypertension, and blood glucose. Six years' incidence of diabetes increased across tertiles of baseline Na-Li CT activity--from 2 to 7%--with a significant linear trend (P < 0.001). In multivariate analyses Na-Li CT is a significant predictor of diabetes independent of age, BMI, HDL cholesterol, hypertension, and plasma glucose; based on exponentiation of the regression coefficient Na-Li CT higher by 154 micromol (i.e. 1 SD of the population mean) was associated with a 36% greater risk of incident diabetes. CONCLUSIONS: Prospective data from the present study show for the first time enhanced Na-Li CT activity is a significant predictor of development of diabetes in adults, thus suggesting that it could be viewed as a pre-clinical, possibly genetic, marker of inherited susceptibility to type 2 diabetes.
BACKGROUND: Previous studies have shown conflicting data on accuracy of equations for kidney function prediction. The present work analysed the relationship of gender, age and body mass index (BMI) to error of predictions by the Cockcroft-Gault equation (CG(eq)), the simplified equation of the Modification of Renal Diseases Study (MDRD(eq)) and the Mayo Clinic equation (Mayo(eq)). METHODS: Inulin clearance (glomerular filtration rate; GFR) and other variables were measured in 380 subjects of both sexes, aged 18-88 years, with and without kidney disease. GFR was defined as low when <60 ml/min x 1.73 m2. BMI was used for definition of underweight/overweight. Relative error of predictions was used as an index of bias. It was calculated as prediction minus GFR (positive values =overestimates, negative values = underestimates) and expressed as a percentage of the GFR. Absolute error was used as an index of imprecision and was calculated as the absolute value of relative error. RESULTS: CG(eq) relative error was inversely associated with age and directly associated with BMI (P<0.001), but not with gender or GFR. MDRD(eq) relative error was inversely associated with female gender and GFR (P<0.001), but not with age or BMI. Mayo(eq) relative error was directly associated with male gender, BMI and GFR (P<0.01), but not with age. Absolute error was higher for CG(eq) than for MDRD(eq) but only at low GFR (P<0.001). Mayo(eq) had a higher absolute error than CG(eq) and MDRD(eq) (P<0.01). CONCLUSIONS: Errors of predictions varied not only with GFR but also with gender, age and BMI. Without using creatinine assay calibration, Mayo(eq) was less accurate than both MDRD(eq) and CG(eq), whereas MDRD(eq) was slightly more precise than CG(eq) but only at low GFR.
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The moderate increase in urinary albumin excretion defined as microalbuminuria is not rare and is associated with cardiovascular risk factors. Microalbuminuria prevalence is low in the absence of cardiovascular risk factors and progressively increases with the number cardiovascular risk factors. The main correlate of microalbuminuria is blood pressure, either systolic or diastolic pressure. The relation between blood pressure and microalbuminuria is continuous and graded because the microalbuminuria prevalence increases with the severity of hypertension. Among hypertensive patients on drug treatment, blood pressure control is associated with a low prevalence of microalbuminuria. Thus, blood pressure appears as a determinant of microalbuminuria rather than a mere correlate. For hypercholesterolemia, smoking, and diabetes, data are less strong but point to an independent positive association with microalbuminuria. Altogether, data indicate that microalbuminuria in the population reflects the presence of cardiovascular risk factors. Data on microalbuminuria and coronary heart disease support this idea. There is a continuous and graded relation between urinary albumin excretion and coronary heart disease prevalence. High urinary albumin excretion is likely a sign of vascular damage existing both at the renal and cardiac levels and induced by 1 or more uncontrolled cardiovascular risk factors.
Since the very early manned missions in space, a state of anemia associated with reduced erythropoietin levels and reduced plasma volume was disclosed. The reduction in red blood cell mass is driven by a process of selective hemolysis, which has been named neocytolysis. This phenomenon also occurs in people living at a high altitude who descend rapidly to sea level. The origin of the signal leading to destruction of newly produced red blood cells probably is located in central circulation, but the operating mechanism is unknown. The importance of plasma cell volume reduction in the genesis of a lower red cell mass also is supported by the inverse correlation seen at moderate altitude. People arriving at moderate altitude have increased erythropoietin concentration that decreases after a few days and is in inverse correlation with central venous pressure. Studies under simulated microgravity conditions in human beings (bed rest, head-down tilt at -6 degrees , water immersion) and in rats provide further insight in unraveling the mechanism of astronauts' anemia, a problem difficult to study in space because of the limited availability of spaceflights.
The intravascular volume consists of 40% to 45% red cells. Their production is controlled predominantly by erythropoietin (EPO), a hormone that is secreted particularly when tissue hypoxia is present. Because of this high percentage of the total intravascular volume the question comes to mind that, in addition to hypoxia, can volume-regulation mechanisms, known to be responsible for the maintenance of plasma volume, modulate EPO secretion when the total vascular volume changes? Indeed, there is evidence that in situations in which the intravascular volume or specifically the intrathoracic volume is altered, EPO secretion is affected. EPO secretion increases when the intrathoracic volume decreases 24 hours after water immersion or after endurance exercise when a negative water balance prevails. A head-down tilt on the other side induces central engorgement leading to a decrease of EPO concentrations. Under these experimental conditions no hypoxia was seen, supporting the idea that a volume stimulus outgoing from intrathoracic parts of the circulation modulated EPO secretion. Further observations from the clinical side are needed to support these ideas and the consequences need to be implemented into clinical practice.
Renal dysfunction is a constant feature of congestive heart failure and is a stronger predictor of mortality than left ventricular ejection fraction or New York Heart Association classification. In heart failure, a reduction of glomerular filtration rate and renal plasma flow occurs, although the filtration fraction increases. There are many reason for this pattern. A reduction in effective circulating volume stimulates sympathetic activity and the renin-angiotensin-aldosterone system, and it is associated with increased concentrations of atrial natriuretic peptide, brain natriuretic peptide, and tumor necrosis factor alpha. Because in chronic kidney disease heart dysfunction commonly is present, an efficient cardiologist-nephrologist interaction should be promoted.
Clinical studies indicate that indices of glomerular filtration rate (GFR) as serum creatinine or creatinine clearance can predict the risk of death in congestive heart failure (CHF) and in heart transplantation. The study reports data on creatinine clearance before and after heart transplantation in 160 patients followed-up for 5 years at our Unit. Pre-transplant creatinine clearance averaged 83.5+/-32 mL/min x 1.73 m(2) and was not significantly associated with 5-year mortality. Creatinine clearance significantly decreased after heart transplantation with a linear trend up to 3 years for patients with complete follow-up. Data suggest that the relation between kidney function and mortality after heart transplantation is affected by several confounders with inclusion of cause of heart disease, co-morbidity, anemia, and post-transplant decrease in kidney function.
This article reviews bone adaptation to microgravity, during manned space missions, in humans undergoing Head Down Tilt (HDT) and in Hind-Limb-Suspended Rats. Under microgravity conditions, bone loss occurs in association with hypercalciuria, which in turn modulates Aquaporin 2 (AQP2) excretion in urine, thus avoiding stone forming in space. This report discloses the need to prevent bone loss in order to prepare for long stays at lunar bases or voyages to Mars.
BACKGROUND: Vascular access thrombosis is an important cause of morbidity in patients with end-stage renal failure on maintenance hemodialysis (MHD). However, little is known about its risk factors. The present study was undertaken to evaluate the role of coagulation factors, fibrinolytic factors, and anti-phospholipid antibodies (aPL). In particular, we have evaluated the role of anti-protein C and anti-protein S antibodies in patients on MHD with and without thrombosis because no data are available in the literature. METHODS: The study group comprised 30 patients with thrombotic complications (TC), 40 patients matched for age, sex, and dialytic age with no thrombotic complications (NTC) and 400 controls. We have measured: anti-protein C antibodies, anti-protein S antibodies, anticardiolipin antibodies (ACA), anti-beta2-glycoprotein antibodies (beta2-GPI), and anti-prothrombin antibodies (aPT), along with prothrombin time, fibrinogen, plasminogen, protein C, protein S, anti-thrombin III, APC-resistance test, D-dimer, tissue-type plasminogen's activator, plasminogen activator inhibitor-1 (PAI-1), prothrombin fragment 1+2, factors of the intrinsic and extrinsic pathway, C-reactive protein, and homocysteine. RESULTS: There were no significant differences between groups for prothrombin time, fibrinogen, plasminogen, protein C, protein S, anti-thrombin III, activated protein C (APC) resistance, D-dimer, tPA, C-reactive protein, Factors II, X, and VII. The anti-beta2-GP1 and aPT were elevated in both TC and NTC patients, compared to the control group. Significant differences between TC and NTC groups were found for anti-protein C and anti-protein S antibodies, ACA-IgM, PAI-1, Factor VIII, prothrombin fragments 1+2, and homocysteine. CONCLUSION: The most novel finding was a significant elevation of anti-protein C antibodies and anti-protein S antibodies in the TC group (i.e., in patients on MHD with thrombosis of vascular access). It indicates that other pathogenetic mechanisms in addition to endothelial damage may cause hypercoagulability in uremia.
Clinical practice became clinical science in the years 1720-1820. There were many reasons for this transformation. The discoveries by Santorio Santorio, William Harvey, Marcello Malpighi, Giovanni Alfonso Borelli, Lorenzo Bellini, Thomas Sydenham, Giovanni Maria Lancisi, were perceived by students who asked for changes in the medical curriculum. In 1761 Morgagni centered the study of diseases on morbid anatomy, a way to control at autopsy the validity of diagnosis. J.P. Frank who worked on public health and John Locke who supported a method of scientific reasoning based on asking questions were also instrumental for changes. Hospitals, formerly hospices for the poor, became places for curing and healing. Military hospitals represented models to be followed. In Vienna Marie Therese inaugurated the Allegemein Krankenhaus in 1785. In revolutionary France Fourcroy with the law Frimaire An III, 1794 gave a new rationale. Medicine and surgery were unified in the curriculum. Basic sciences were introduced. Dissection became compulsory, practical teaching became the rule. But it was with John Hunter, Domenico Cotugno and P. Joseph Desault that the great advancement was achieved. They were anatomists and therefore they made the knowledge of human body the core of medical curriculum. However experimentation on animals, as well as practical bedside teaching at the hospital also became important. Through their work hospitals and universities were associated in a common goal.
BACKGROUND: Female gender is associated with high erythropoietin (EPO) resistance in end-stage renal disease. The aim of our study was to investigate the roles of age and menstrual status in this relationship. METHODS: Cross-sectional analysis of registry data for 3,224 hemodialysis adults treated with EPO. Data collection included gender, age, weight, height, dialytic age, hemoglobin, EPO dose, and, for women with ages 25-44 only, also information on menstrual status and iron homeostasis. EPO resistance index (ERI) was calculated as EPO dose per kilogram BW/hemoglobin. RESULTS: Men and women had not significantly different hemoglobin and significantly different EPO dose per kilogram weight (women vs. men, +18.2%, p < 0.001). Thus, ERI was higher in women than in men (+19.5%, p < 0.001). The gender-associated difference in ERI linearly decreased along age groups: +30.9% for ages 25-44, +23.2% for ages 45-64, and +14.2% for ages 65-84 (p < 0.05 for interaction between age and gender-associated difference in ERI). Within the subgroup of women with ages 25-44, women with menses in comparison to women without had 44.6% higher ERI (p < 0.01) due to combination of lower hemoglobin (p < 0.05) with higher EPO dose (p < 0.001). Women with menses had also lower serum iron, transferrin saturation, and serum ferritin (p < 0.001). CONCLUSION: The gender-associated difference in ERI is lower with increasing patients' age. The large difference between young men and women is due to women with menses who have iron deficiency more frequently than women without periods.
BACKGROUND: Previous studies report that urinary albumin excretion is associated with coronary heart disease (CHD). The present epidemiologic study investigated if (1) blood pressure status affects the association of urinary albumin excretion with CHD; and (2) urinary albumin excretion is associated with low renal function also. METHODS: The cross-sectional association was analyzed of overnight urinary albumin excretion with prevalence of CHD (myocardial infarction and/or ischemia as defined by standard electrocardiogram) and low renal function (overnight creatinine clearance <60 mL/min) in a population sample of 1632 men and women with ages 45 to 64 years. Hypertension, hypercholesterolemia, smoking habit, and diabetes mellitus were included in analyses. RESULTS: CHD prevalence was in the whole sample 8.2% (N= 134), in the hypertensive subgroup 11.9% (N= 79), and in the nonhypertensive subgroup 5.7% (N= 55). For the association between urinary albumin excretion (logarithm-transformed due to skewed distribution) and CHD, the multivariate logistic coefficient with 95% CI was significant in the whole sample (+0.79, 95% CI =+0.32/+1.26, P < 0.001) and in the hypertensive subgroup (+0.97, 95% CI =+0.70/+1.24, P < 0.001), not in the nonhypertensive subgroup (-0.06, 95% CI =-0.80/+0.68, P= 0.997). Prevalence of low creatinine clearance was in the whole sample 4.0% (N= 66), in the hypertensive subgroup 4.8% (N= 32), and in the nonhypertensive subgroup 3.5% (N= 34). The logistic coefficient between urinary albumin excretion and low creatinine clearance was borderline significant in the whole sample (+0.56, 95% CI =-0.02/+1.14, P= 0.090), significant in the hypertensive subgroup (+0.73, 95% CI =+0.04/+1.42, P= 0.044), not significant in the nonhypertensive subgroup (-0.07, 95% CI =-1.25/+1.10, P= 0.913). CONCLUSION: Results support the use of urinary albumin excretion as marker of CHD and slightly reduced renal function in hypertensives.