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Biomedical subjects

A Donati

Publications and source records attributed to A Donati.

At least 19 recordsLinked to original sources

Fluid challenge in patients submitted to spinal block.

AIM: The practice of routinely prehydrating patients by infusing a colloid solution for prevention of spinal anesthesia-induced hypotension has been challenged recently. The aim of the study was to evaluate the influence of a 15 mL/kg pre-emptive bolus of colloids (6% hydroxyhethyl starch) on heart rate (HR), mean arterial blood pressure (MAP), cardiac index (CI) in patients submitted to subarachnoid block with hyperbaric bupivacaine 0.5%, 0.2 mg/kg for orthopedic surgery of the lower limb. METHODS: Patients were monitored by a Model Flow method. Forty patients (ASA I-II) scheduled to undergo to spinal anesthesia for elective orthopedic surgery of the lower limb were enrolled in the study. The 20 patients in Group A were treated with a preanesthetic infusion of 15 mL/kg of hydroxyhaethyl starch 6%, Group B (20 untreated patients) was the control group. HR, MAP, CI were collected at T0 (first relevation); T1 (after 5 min from the spinal block); T2 (after 10 min); T3 (after 15 min); T4 (after 20 min); T5 (after 25 min); T6 (after 30 min); T7 (after 35 min). RESULTS: Our data show that MAP value is higher in treated patients than in control group (ANOVA: P<0.001) and at T1 in Group B MAP was lower than at T0 (P<0.05). HR and CI trend appear similar in the 2 groups. Our results show that heart rate is not affected by colloid infusion. This may be due to the substantial cardiovascular stability of the selective spinal anesthesia, which does not activate a clinical relevant compensatory vagal effect. Fluid prehydration would expand the vascular space and hence compensate for the reduction in systemic vascular resistance, although MAP reduction following the induction of spinal anesthesia is present in both treated and control groups. CONCLUSION: Our data show that despite to fluid challenge, we could not prevent MAP decrease in Group A, even if it is more marked in Group B.

Aged↗

Successful early voriconazole treatment of Aspergillus infection in two non immunocompromised patients in Intensive Care Unit.

We report two cases of respiratory Aspergillus infection that occurred in patients admitted to the Intensive Care Unit of a teaching hospital during renovation works and treated with new triazole voriconazole (Vfend). The first patient was affected with cerebral hemorrhage, the second with polytrauma and both developed Aspergillus Pneumonia during their ICU stay. Bronchoalveolar lavage, dosage with anti-Aspergillus antibodies, antigen measurements and galactomannan research with Sanofi Platelia were performed. Therapy was carried out with voriconazole for 12 days. Chest X-ray and laboratory tests showed complete resolution after 12 days of therapy; clinical symptoms were negative after 4 days. Aspergillus infection can be observed frequently in non-immunocompromised patients during ward renovation or in hospitals near building areas. Since treatment is often unsuccessful, we preferred to immediately employ new agents to reduce the impact of this disease.

Antifungal Agents↗

The greenhouse gas balance of the Province of Siena.

There is a profound debate over how to assign greenhouse gas (GHG) responsibilities; therefore, we have decided to follow IPCC guidelines, as they offer the only standardized method. We have identified each type of greenhouse emission and its level of absorption. We have studied the province and its districts and municipalities. We have determined that the energy sector is that with the highest level of emissions, even if the per capita emissions of the Province of Siena are very low. This is caused by a very low level of industrialization and the presence of a local geothermal production of energy. In order to highlight this aspect, we have considered scenarios both with and without geothermal production. Our research was then focused on single districts (groups of homogenous municipalities) and municipalities, where we found great differences among the greenhouse emissions of the areas. We have constructed a map of the greenhouse emissions of the whole province. It has been interesting to note that there are 14 municipalities with net negative emissions, seven with low positive emissions, 12 with medium positive emissions and three with elevated positive emissions. These latter correspond to the main city and to two of the most industrialized municipalities.

Carbon Dioxide↗

Dietary restriction counteracts age-related changes in cholesterol metabolism in the rat.

The effects of ageing on the metabolism of cholesterol were examined in three different organs (liver, aorta and brain) of 6-, 12- and 24-month-old male Sprague-Dawley rats. Ageing was associated with a significant increase in intracellular cholesterol esters in all three organs. Steady state mRNA levels of multidrug resistance protein (MDR) and acylCoA:cholesterol acyl transferase (ACAT), enzymes involved in cholesterol import and esterification, were also increased. By contrast, expression of mRNA for neutral cholesterol ester hydrolase (nCEH) and caveolin-1, proteins involved in cholesterol ester hydrolysis and export, were significantly reduced. Dietary restriction is the only intervention shown to extend lifespan and retard age-related declines in function in mammals. To further explore the possible correlation between changes in cholesterol esterification and ageing, we analysed cholesterol metabolism in liver, aorta, and brain of aged rats exposed to two dietary restriction regimens: intermittent (alternate-day) fasting (IF) and food intake restriction (60% of ad libitum feeding). Both dietary regimens attenuated the age-related changes in cholesterol esters and in the expression of genes involved in cholesterol metabolism. These results provide evidence that distinctive age-associated changes in intracellular cholesterol metabolism occur in rats. Furthermore, these modifications can be partially reversed by dietary restriction, a condition known to affect the ageing process. Age-related changes in cholesterol metabolism may play a role in triggering and/or aggravating senescence-related disorders characterized by altered cholesterol homeostasis.

Aging↗

Effects of aging and anti-aging caloric restrictions on carbonyl and heat shock protein levels and expression.

Heat shock proteins (Hsps) are induced by stressful stimuli and have been shown to protect cells and organs from such stresses both in vitro and in vivo, and play a positive role in lifespan determination. An attenuated response to stress is characteristic of senescence and no Hsp induction is observed upon exposure to stress and no protective effect of a mild stress is observed in cells from aged individuals. The artificial over-expression of Hsps, can produce a protective effect against a variety of damaging stimuli in cells from aged rats or aged humans, in whom cardiovascular disease is a major cause of morbidity in older age. Here, we show that aging significantly decreases the levels of Hsp27, Hsp60, Hsp72 and Hsc70 in right atrium and left ventricle of the rat heart, both at level of protein and of mRNA. Two different caloric restriction regimens have been found to counteract in part the decrease in the levels of Hsp expression in the aged heart tissue as well as the tendency to an increase of the levels of carbonyl in cardiac proteins. Our data suggest that cardiac Hsp levels may be a determinant of longevity in rodents, and that generation of new regimens of caloric restriction may eventually show how to improve modulation of cardiac aging.

Aging↗

Efficacy of ACE-inhibitor therapy on renal disease in glycogen storage disease type 1: a multicentre retrospective study.

BACKGROUND: The efficacy of ACE-inhibitors in decreasing microalbuminuria and proteinuria has been reported in a few patients with glycogen storage disease type 1 (GSD1); however, no case-control study has ever been published. AIM: The aim of the current study was to evaluate the efficacy of ACE-inhibitors in reducing glomerular hyperfiltration, microalbuminuria and proteinuria, and in delaying the progression of renal damage. PATIENTS AND METHODS: Ninety-five patients (median age at the time of the study: 14.5 years) were enrolled from nine Italian referral centres for metabolic diseases. A retrospective study of a 10-year follow-up was conducted in order to compare the evolution of these parameters in treated patients with those who were not treated with ACE-inhibitors. RESULTS: A significant and progressive decrease of glomerular filtration rate was observed in treated patients vs. those who were not treated with ACE-inhibitors (P < 0.05). No difference was observed for microalbuminuria and proteinuria between the two groups of patients. Moreover, the ACE-inhibitors significantly delayed the progression from glomerular hyperfiltration to microalbuminuria, but not that from microalbuminuria to proteinuria. CONCLUSIONS: The results of the present study underline the importance of a strict follow-up of renal function in GSD1 patients. The detection of glomerular hyperfiltration suggests precocious initiation of ACE-inhibitor treatment to delay the progression of renal damage. A randomized prospective study is needed to establish for certain the real effectiveness of this treatment in GSD1 patients.

Adolescent↗

Haemodynamic modifications after unilateral subarachnoid anaesthesia evaluated with transthoracic echocardiography.

AIM: The aim of the study is the evaluation through transthoracic echocardiography of the haemodynamic modifications due to unilateral subarachnoid anaesthesia with bupivacaine 0.5% given for orthopaedic surgery. METHODS: In this prospective study, at the University Hospital Orthopedics surgical theater, 20 patients underwent orthopaedic surgery on the lower limbs. Unilateral spinal block was performed with hyperbaric bupivacaine 0.5%, 8 mg after a fluid challenge with saline solution 0.9%. Transthoracic echocardiography was performed and cardiac output was calculated from the left ventricular outflow tract (LVOT) with a recently validated technique. Cardiac output, stroke volume, ejection fraction, heart rate, mean arterial pressure were evaluated. These parameters were obtained before anaesthesia (t1), 5 minutes after anaesthesia (t2) and 16 minutes after anaesthesia (t3). RESULTS: Systolic, mean and diastolic arterial pressures after 5 min and 16 min from anaesthesia significantly decreased if compared to basal time (p<0.05 and p<0.001 respectively) while cardiac index (p<0.001) and ejection fraction (p<0.05) decreased only after 16 min from subarachnoid anaesthesia. CONCLUSION: Despite the fluid challenge we can not prevent a significant fall in the blood pressure and a decrease of the left ventricular function calculated with the decrease of cardiac output and of the left ventricular ejection fraction.

Adult↗

Correlation between hyperglycemia and mortality in a medical and surgical intensive care unit.

AIM: The aim of this study was to assess the correlation between hyperglycemia and mortality in a group of patients admitted to a medical and surgical ICU and to evaluate if the association between hyperglycemia and reason of ICU admission significantly worsens patients' outcomes. METHODS: A retrospective clinical study was conducted in the ICU of a University Hospital. Four-hundred and twelve adult patients admitted to our ICU were enrolled. The blood glucose level was measured at the time of admission and daily at 2-4 h intervals. When the glucose level exceeded 180 mg/dL, an insulin bolus or a continuous infusion were performed to maintain the glucose level at or below 180-200 mg/dL. RESULTS: Analysing the mean blood glucose levels of patients with the receiver operating characteristic (ROC) curve, it resulted that the blood glucose level of 141.7 mg/dL had higher sensitivity (76%) and specificity (56.5%) to discriminate the probability of death. In other words, in patients in whom the mean blood glucose levels were greater than 141.7 mg/dL, the probability of death was higher (26.62%) than in the group of patients in whom a strict blood glucose control was maintained (13.55%) (P = 0.0017). CONCLUSIONS: A strict blood glucose control seems to be crucial, even in a medical and surgical ICU. The need for intensive insulin therapy, even by means of continuous infusion of insulin, to obtain the normalization of blood glucose levels, appears essential.

Blood Glucose↗

A new and feasible model for predicting operative risk.

BACKGROUND: Although the POSSUM (Physiological and Operative Severity Score for the enumeration of Mortality and Morbidity) score can be used to calculate operative risk, its complexity makes its use unfeasible in the immediate clinical setting. The aim of this study was to create a new model, based on ASA status, to predict mortality. METHODS: Data were collected in two hospitals. All types of surgery were included except for cardiac surgery and Caesarean delivery. Age, sex and preoperative information, including the presence of cardiocirculatory and/or lung disease, renal failure, diabetes mellitus, hepatic disease, cancer, Glasgow Coma Score, ASA grade, surgical diagnosis, severity of the procedure and type of surgery (elective, urgent or emergency), were recorded for each patient. The model was developed using a data set incorporating data from 1936 surgical patients, and validated using data from a further 1849 patients. Forward stepwise logistic regression was used to build the model. Goodness of fit was examined using the Hosmer-Lemeshow test and receiver operating characteristic (ROC) curve analyses were performed on both data sets to test calibration and discrimination. In the validation data set, the new model was compared with POSSUM and P-POSSUM for both calibration and discrimination, and with ASA alone to compare discrimination. RESULTS: The following variables were included in the new model: ASA status, age, type of surgery (elective, urgent, emergency) and degree of surgery (minor, moderate or major). Calibration and discrimination of the new model were good in both development and validation data sets. This new model was better calibrated in the validation data set (Hosmer-Lemeshow goodness-of-fit test: chi(2)=6.8017, P=0.7440) than either P-POSSUM (chi(2)=14.4643, P=0.1528) or POSSUM, which was not calibrated (chi(2)=31.8147, P=0.0004). POSSUM and P-POSSUM had better discrimination than the new model, although this was not statistically significant. Comparing the two ROC curves, the new model had better discrimination than ASA alone (difference between areas, 0.077, SE 0.034, 95% confidence interval 0.012-0.143, P=0.021). CONCLUSIONS: This new, ASA status-based model is simple to use and can be performed routinely in the operating room to predict operative risk for both elective and emergency surgery.

Adolescent↗

The role of macroautophagy in the ageing process, anti-ageing intervention and age-associated diseases.

Macroautophagy is a degradation/recycling system ubiquitous in eukariotic cells, which generates nutrients during fasting under the control of amino acids and hormones, and contributes to the turnover and rejuvenation of cellular components (long-lived proteins, cytomembranes and organelles). Tight coupling between these two functions may be the weak point in cell housekeeping. Ageing denotes a post-maturational deterioration of tissues and organs with the passage of time, due to the progressive accumulation of the misfunctioning cell components because of oxidative damage and an age-dependent decline of turnover rate and housekeeping. Caloric restriction (CR) and lower insulin levels may slow down many age-dependent processes and extend lifespan. Recent evidence is reviewed showing that autophagy is involved in ageing and in the anti-ageing action of anti-ageing calorie restriction: function of autophagy declines during adulthood and is almost negligible at older age; CR prevents the age-dependent decline of autophagic proteolysis and improves the sensitivity of liver cells to stimulation of lysosomal degradation; protection of autophagic proteolysis from the age-related decline co-varies with the duration and level of anti-ageing food restriction like the effects of CR extending lifespan; the pharmacological stimulation of macroautophagy has anti-ageing effects. Besides the involvement in ageing, macroautophagy may have an essential role in the pathogenesis of many age-associated diseases. Higher protein turnover may not fully account for the anti-ageing effects of macroautophagy, and effects of macroautophagy on housekeeping of the cell organelles, antioxidant machinery of cell membranes and transmembrane cell signaling should also be considered.

Aging↗

Solution structure of folic acid. Molecular mechanics and NMR investigation.

The structure of folic acid in solution was investigated by nuclear magnetic resonance (NMR) and theoretical calculations. Dynamical information and geometrical constraints were obtained by carbon-13 relaxation study, homo-nuclear NOESY spectra and hetero-nuclear 1H-13C NOE experiments. This set of experimental data was used for the molecular mechanics and molecular dynamic calculations. The accuracy of the final structure was established by the R(NMR) factor, which was calculated comparing the experimental NOESY cross-peaks intensities and the corresponding values simulated by using the complete relaxation matrix analysis (CORMA) approach.

Carbon Isotopes↗

Ageing and oxidative stress: a role for dolichol in the antioxidant machinery of cell membranes?

Dolichol is a polyprenol compound broadly distributed in membranes, biosynthetized by the general isoprenoid pathway from acetate via mevalonate and farnesyl pyrophosphate. Dolichol lays inside the membrane between the two leaflets of the lipid bilayer very close to the tail of phospholipid fatty acids. No definite catabolic pathways for this molecule have yet been identified. Evidence is produced that dolichol levels increase dramatically with increasing age; that anti-ageing caloric restriction retards this age-associated change; that dolichol may act as a radical scavenger of peroxidized lipids belonging to the cell membranes. In view of the polyunsaturated fatty acids (PUFA), dolichol and Vitamin E location and stechiometry, it is proposed that molecules might interact each-other to form a highly matched free-radical-transfer chain, whose malfunctioning might be involved in statin toxicity and neurodegenerative diseases.

Aging↗

To verify four 5-year-old mathematical models to predict the outcome of ICU patients.

AIM: The aim of this study is to verify calibration and discrimination after 5 years in the case mix of patients admitted to the Intensive Care Unit (ICU) during the year 2000. In this way we want to perform a quality control of our ICU in order to justify the increased amount of money spent for intensive care. METHODS: A prospective study has been made on the 357 patients admitted to the ICU during the year 2000. The Apache II score was calculated within the first 24 hours and, depending on the length of stay in the ICU, on the 5(th), 10(th) and 15(th) day after ICU admission. On the basis of the 4 mathematical models death risk has been calculated for each of the 4 times. The Hosmer-Lemeshow test was performed for calibration and ROC curves for discrimination, always for each of the 4 mathematical models. RESULTS: The 1(st) model, at 24 hours from ICU admission, showed a bad calibration (p=0.000088), while the ROC curve was 0.744+/-0.32. Also the 2(nd) model, at the 5(th) day from admission, showed a bad calibration (p=0.000588), with ROC curve of 0.827+/-0.04. The 3(rd) model (10(th) day), was well calibrated (p=0.112247) and discriminating (ROC=0.888 +/-0.04). Finally the models at 15 days showed again a bad calibration (p=0.001422) but a very good discrimination (area=0.906+/-0.06). CONCLUSION: Developing mathematical models to predict mortality within ICUs can be useful to assess quality of care, even if these models should not be the only ICU quality controls, but must be accompanied by other indicators, looking at quality of life of the patients after ICU discharge.

Critical Care↗

Transesophageal Doppler ultrasonography evaluation of hemodynamic changes during videolaparoscopic cholecystectomy.

BACKGROUND: The aim of this study was to assess the changes of hemodynamic and oxyphoretic parameters induced by pneumoperitoneum in a series of patients undergoing laparoscopic cholecystectomy, by using the transesophageal Doppler ultrasonography (TEDU). METHODS DESIGN: prospective study. SETTING: a medico-surgical intensive care unit of an University Hospital. PATIENTS: 11 patients who underwent laparoscopic cholecystectomy because of gallbladder stones. INTERVENTIONS: a central venous line, a radial artery line were placed before the induction of anesthesia. End expiratory CO2 (EtCO2) was monitored by using a capnometer (Dräger, Germany). Cardiac output (CO) was measured using the transesophageal Doppler system Abbott ODM II (Abbott Critical Care Systems, Ireland), which was positioned in the esophagus after stabilization of anesthesia. MEASUREMENTS: hemodynamic parameters, including CO, central venous pressure, mean arterial pressure, measurement of EtCO2 and arterial and central venous samples were performed: after reaching a stable anesthesia but before any surgical manipulation (T0); after induction of pneumoperitoneum (T1); 15 min after T1 (T2); 30 min after T1 (T3). RESULTS: SVR increased significantly at T1 and T2 compared to T0; PaCO2 and PvCO2 at T2 and T3. HR and MAP increased significantly at T1, and CVP significantly at all the times. CONCLUSIONS: Laparoscopic surgery is a mini-invasive technique of increasing success among both surgeons and patients. The widening of candidate patients raises the question of eligibility for individuals with known cardiopulmonary disease. In these patients, only a careful and thorough anesthesiologic monitoring allows the prompt identification and treatment of any relevant hemodynamic and/or ventilatory changes.

Adult↗

Clinical and molecular findings in hyperornithinemia-hyperammonemia-homocitrullinuria syndrome.

The authors report the clinical and molecular findings in eight patients with hyperornithinemia, hyperammonemia, and homocitrullinuria (HHH) syndrome. The most consistent neurologic finding was spastic paraparesis, seen in five of the eight patients. However, all showed signs of pyramidal tract involvement. A broad spectrum of pathogenetic mutations (including missense, nonsense, splice site, insertion, and deletions) were identified in the ORNT1 gene.

Adolescent↗

Solution structure of hyaluronic acid oligomers by experimental and theoretical NMR, and molecular dynamics simulation.

The conformational properties of hyaluronic acid (HA) oligomers in aqueous solution were investigated by combining high-resolution NMR experimental results, theoretical simulation of NMR two-dimensional (2D) spectra by Complete Relaxation Matrix Analysis (CORMA), and molecular dynamics calculations. New experimental findings recorded for the tetra- and hexasaccharides enabled the stiffness of the HA and its viscoelastic properties to be interpreted. In particular, rotating frame nuclear Overhauser effect spectroscopy spectra provided new information about the arrangement of the glycosidic linkage. From (13)C NMR relaxation the rotational correlation time (tau(c)) were determined. The tau(c) were employed in the calculation of geometrical constraints, by using the MARDIGRAS algorithm. Restrained simulated annealing and 1 ns of unrestrained molecular dynamic simulations were performed on the hexasaccharide in a box of 1215 water molecules. The beta(1 --> 3) and beta(1 --> 4) glycosidic links were found to be rigid. The lack of rotational degree of freedom is due to direct and/or water-mediated interresidue hydrogen bonding. Both single or tandem water bridges were found between carboxylate group and N-acetil group. The carboxylate group of glucuronic acid is not involved in a direct link with the amide group of N-acetyl glucosamine and this facilitated bonding between the residue and the water molecules.

Biopolymers↗