Bonomini M.,University of Chieti Pescara |
Zammit V.,Clinical science Research Institute |
Pusey C.D.,Imperial College London |
De Vecchi A.,Policlinico Hospital |
Pharmacological Research | Year: 2011
Anemia is one of the most frequent complications of kidney failure and a common cause of morbidity in dialysis patients. A number of clinical studies have suggested that l-carnitine (LC), a naturally occurring compound involved in bioenergetic processes, may alleviate the anemia of hemodialysis patients. Since LC deficiency is commonly present in dialysis patients, LC has been described as a "conditional vitamin". However, the use of LC supplementation in dialysis remains controversial as well as its mode of action in preventing anemia. Recent literature shows that to fully exploit its pharmacological potential, LC may have to be administered at doses that achieve supra-physiological levels of LC in plasma and target organs. However, this concept has not been fully investigated in uremic patients. In this article, we will review the use of LC in dialysis patients, and provide a rationale for the anti-anemic action of LC based on biophysical, metabolic and antiapoptotic effects of this compound on erythropoiesis and the function of mature, circulating erythrocytes. The discussion will be focused on experimental and clinical data that support the concept that supra-physiological concentrations of LC may improve the anemic condition of dialysis patients, as would be expected from a "conditional drug" rather than a "conditional vitamin". © 2010 Elsevier Ltd.
Giordano D.,Policlinico Hospital |
Quattrone S.,Policlinico Hospital |
Pintaudi B.,Messina University |
Di Benedetto A.,Messina University
Menopause | Year: 2011
Objective: The aim of this study was to evaluate whether myo-inositol, an insulin-sensitizing substance, may improve some features of metabolic syndrome in postmenopausal women. Methods: Eighty postmenopausal women affected by the metabolic syndrome were enrolled prospectively in the study and treated with diet plus supplementation of myo-inositol (2 g BID plus diet: intervention group) or with diet plus placebo (control group) for 6 months. They were evaluated at baseline and after 6 months for insulin resistance (homeostasis model assessment ratio [HOMA] insulin resistance), lipid profile, and blood pressure. Results: Myo-inositol plus diet improved systolic and diastolic blood pressure, HOMA index, cholesterol, and triglyceride serum levels with highly significant differences, compared with the groups treated only with diet and placebo. In the group treated with myo-inositol, a decrease in diastolic blood pressure (-11%), HOMA index (-75%), and serum triglycerides (-20%) and an improvement in high-density lipoprotein cholesterol (22%) were shown. Conclusions: Supplementation with myo-inositol may be considered a reliable option in the treatment of metabolic syndrome in postmenopausal women. © 2011 by The North American Menopause Society.
Galeone A.,University of Bari |
Galeone A.,La Pitie Salpetriere Hospital |
Rotunno C.,University of Bari |
Guida P.,University of Bari |
And 4 more authors.
Journal of Cardiothoracic and Vascular Anesthesia | Year: 2013
Objectives: To assess the incidence of incomplete heparin reversal and heparin rebound after cardiac surgery with cardiopulmonary bypass (CPB) and the ability of the activated coagulation time (ACT) and thromboelastography (TEG) to detect these phenomena. Design: Prospective single-center study. Setting: University hospital. Participants: Forty-one patients undergoing elective cardiac surgery with CPB and with normal preoperative TEG parameters. Interventions: ACT, TEG, and plasma heparin levels were measured in all patients at 5 different times between 20 minutes and 3 hours after protamine administration. The variability of TEG reaction time (R) with and without heparinase (delta-R [DR]) was used to detect the presence of residual heparin. Measurements and Main Results: Plasma heparin expressed as anti-FXa activity was detected in 180 (88%) samples. At univariate analysis, ACT, R-kaolin (R-k), and DR significantly correlated with plasma heparin concentration (respectively, p = 0.007, p = 0.006, and p = 0.002). At multivariate analysis, R-k and DR remained associated with plasma heparin concentration (respectively, p = 0.014 and p = 0.004). Greater quartiles of heparin were associated with higher values of R-k and DR. Combined procedures had significantly lower DR than isolated procedures (p = 0.017), and CPB time and heparinization time positively correlated with R-k (respectively, p = 0.044 and p = 0.022). No association was observed between heparin concentration, ACT, and TEG parameters with postoperative bleeding and need for blood and blood components transfusions. Conclusions: Heparin rebound and incomplete heparin reversal are very common phenomena after cardiac surgery with CPB; ACT is not able to detect residual heparin activity, whereas TEG analysis with and without heparinase allows the diagnosis of heparin rebound. © 2013 Elsevier Inc.
Iudicello A.,Policlinico Hospital |
Alberghini L.,Maggiore Hospital |
Benini G.,Maggiore Hospital |
Mosconi P.,Irccs Instituto Of Ricerche Farmacologiche Mario Negri
Trials | Year: 2016
Therapeutic use of an unauthorised drug (or of an authorised drug for an unauthorised indication) for patients with a life-threating disease is permitted outside a clinical trial as an Expanded Access Programme (EAP). The regulations regarding EAPs is not the same all over the world. For example, the recommendation of the European Medicines Agency (EMA) in EU countries also includes within EAPs patients who have been treated in a clinical trial and who wish to continue the treatment. Nevertheless, the patients treated in a clinical trial could have the option of continuing treatment for an extended period in an Open-label Extension study, aimed to generate long-term data on efficacy, safety, tolerability and administration. The aims of this paper - based on the difficulties and incoherence encountered by an Italian Ethic Committee (EC) during the authorisation process of EAPs - are: understanding the origin of this misclassification by analysing differences and similarities among USA, European and Italian regulations concerning EAPs; and showing difficulties in classifying international study protocols as a consequence of the lack of harmonisation of definitions. We performed a critical review of the current USA, European and Italian regulations and we analysed some practical cases by retrieving protocols from Clinicaltrials.gov and the Italian Clinical Trials Registry (OsSC) containing in the title the keywords 'Expanded Access Programme', "'Expanded Access', 'Open-label Extension study' or 'Early Access'. We observed that the Food and Drug Administration ( FDA) definition of EAP is very clear while the EMA definition is similar to that of an Open-label Extension study. This lack of a clear definition generates misclassification and it is possible to find an EAP with an efficacy or safety endpoint; or an EAP managed as a clinical trial; or an EAP classified in Clinical Trials Registries as a phase II, III or IV clinical trial. The internationalisation of the studies requires a harmonisation on a global level of legislation and definitions to eliminate misclassification of protocols. For this reason, the authors suggest that: a) the EMA definition should be harmonised with the FDA definition of EAPs, b) European regulation, even if optional, should be adopted in a compulsory way by national regulations. Moreover, separate registries for both EAPs and clinical trials should be organised. © 2016 Iudicello et al.
PubMed | University of Foggia, Policlinico Hospital, Taranto Local Health Unit and Ferrari
Type: | Journal: Journal of diabetes research | Year: 2016
Surveillance represents a key strategy to control type 1 diabetes mellitus (T1DM). In Italy, national data are missing. This study aimed at evaluating the incidence of T1DM in subjects <18 year olds in Apulia (a large southeastern region, about 4,000,000 inhabitants) and assessing the sensitivity of the regional Registry of Childhood-Onset Diabetes (RCOD) in the 2009-2013 period.We performed a retrospective study matching records from regional Hospital Discharge Registry (HDR), User Fee Exempt Registry (UFER), and Drugs Prescription Registry (DPR) and calculated T1DM incidence; completeness of each data source was also estimated. In order to assess the RCOD sensitivity we compared cases from the registry to those extracted from HDR-UFER-DPR matching.During 2009-2013, a total of 917 cases (about 184/year) in at least one of the three sources and an annual incidence of 25.2 per 100,000 were recorded, lower in infant, increasing with age and peaked in 5- to 9-year-olds. The completeness of DPR was 78.7%, higher than that of UFER (64.3%) and of HDR (59.6%). The RCODs sensitivity was 39.05% (360/922; 95% CI: 34.01%-44.09%).Apulia appeared as a high-incidence region. A full, active involvement of physicians working in paediatric diabetes clinics would be desirable to improve the RCOD performance.
Firetto M.C.,Policlinico Hospital |
Lemos A.A.,Policlinico Hospital |
Marini A.,University of Milan |
Avesani E.C.,University of Milan |
Biondetti P.R.,Policlinico Hospital
Emergency Radiology | Year: 2013
To retrospectively evaluate the frequency and type of findings that were missed in the original reports of multi-detector CT angiography (MDCTA) in patients with suspected acute bowel ischemia. From January 2007 to March 2011, a series of 35 patients who underwent MDCTA of the abdomen and pelvis and had surgery were included. The reports of the initial CT were retrospectively compared with the discharge diagnosis and surgical reports. Discrepant or missing findings were re-evaluated and divided into relevant or not relevant regarding the diagnosis. In 23 of the 35 patients (66 %), all findings were correctly diagnosed in the initial MDCTA report. In the remaining 12 of the 35 patients (34 %), lesions that were not reported were present at surgery. In 10 of the 12 (83 %) patients, the overlooked findings were relevant and subtle: gas in the portal vein (n = 3), gas in the bowel wall (n = 3), gas in the portal vein and bowel wall (n = 2), thrombotic occlusion of the superior mesenteric artery (n = 1), and thrombotic occlusion of the inferior mesenteric artery (n = 1). In 2 of the 12 (17 %) patients in whom the MDCTA-overlooked findings were classified as non-relevant, bowel ischemia was found at surgery. With retrospective image interpretation, 83 % of the patients with occlusive mesenteric ischemia at surgery were correctly identified, whereas the remaining 17 % with non-occlusive mesenteric ischemia at surgery showed non-relevant findings at MDCTA. About 33 % of relevant findings of bowel ischemia were overlooked by the initial MDCTA interpretation, most were subtle findings. However, secondary reading revealed most of these findings and can serve to improve diagnostic performance. © 2012 Am Soc Emergency Radiol.
Lissoni P.,San Gerardo Hospital |
Messina G.,Policlinico Hospital |
Rovelli F.,San Gerardo Hospital
Current Aging Science | Year: 2012
Aging and advanced cancer are characterized by similar neuroendocrine and immune deficiencies; the most important of them consist of diminished nocturnal production of the pineal hormone melatonin (MLT) and decreased production of IL-2. At present, however, it is known that the pineal gland may produce indole hormones other than MLT. The most investigated of them is represented by 5-methoxy-tryptamine (5-MTT), which may exert antitumor, anticachectic, and immunomodulating effects under experimental conditions, in addition to those effects produced by MLT itself. In an attempt to obtain some preliminary data in human subjects about the potential therapeutic properties of 5-MTT, three different studies of 5-MTT have been carried out in advanced solid tumor patients. The first study of MLT plus 5-MTT included 14 thrombocytopenic cancer patients who did not respond to MLT alone. In the second study we have compared the clinical efficacy of MLT plus 5-MTT in a group of 25 untreatable metastatic cancer patients to the results obtained in a control group of 25 cancer patients receiving MLT alone. Finally, the third study of MLT plus 5-MTT included 14 untreatable metastatic cancer patients who did not respond to MLT alone. In all of these studies, MLT and 5-MTT were given orally at the level of 20 mg/day in the evening and at 5 mg/day during the period of maximum light. A normalization of platelet number was achieved by MLT plus 5-MTT in 5 of 14 (36%) thrombocytopenic cancer patients who did not respond to MLT alone. The percentage of disease control obtained by MLT plus 5-MTT in untreatable metastatic cancer patients was significantly higher than that achieved by MLT alone (15/25 [60%] vs. 8/25 [32%], P<0.05). Finally, the association of 5-MTT with MLT induced disease stabilization in 4 of 14 (29%) untreatable metastatic cancer patients who did not respond to MLT alone. © 2012 Bentham Science Publishers.
Agostini A.,University of Bologna |
Benuzzi F.,University of Modena and Reggio Emilia |
Filippini N.,University of Oxford |
Filippini N.,LENITEM Laboratory of Epidemiology |
And 10 more authors.
Neurogastroenterology and Motility | Year: 2013
Background Crohn's disease (CD) is a chronic intestinal disorder characterized by overproduction of inflammatory cytokines and recurrent abdominal pain. Recently, brain morphological abnormalities in the pain matrix were found in patients with chronic pain disorders including irritable bowel syndrome. To investigate potential structural brain changes associated with CD, we used magnetic resonance imaging (MRI). Furthermore, we tested whether in patients gray matter (GM) volumes correlated with disease duration. Methods Eighteen CD patients in remission and 18 healthy controls underwent structural MRI. Voxel-based morphometry (VBM) is a fully automated technique allowing identification of regional differences in the amount of GM enabling an objective analysis of the whole brain between groups of subjects. VBM was used for comparisons and correlation analysis. Key Results With respect to controls, CD patients exhibited decreased GM volumes in portion of the frontal cortex and in the anterior midcingulate cortex. Disease duration was negatively correlated with GM volumes of several brain regions including neocortical and limbic areas. Conclusions & Inferences Crohn's disease is associated with brain morphological changes in cortical and subcortical structures involved in nociception, emotional, and cognitive processes. Our findings provide new insight into the brain involvement in chronic inflammatory bowel disorders. © 2012 Blackwell Publishing Ltd.
Santamaria A.,Messina University |
Giordano D.,Policlinico Hospital |
Corrado F.,Messina University |
Pintaudi B.,Messina University |
And 4 more authors.
Climacteric | Year: 2012
Objective To evaluate the 12-month effect of myo-inositol treatment on some biochemical parameters of women affected by metabolic syndrome. Methods Eighty outpatient postmenopausal women, affected by metabolic syndrome, were enrolled in a 12-month study. All women were treated with a low-energy diet, and then they were randomly assigned to myo-inositol 2 g b.i.d. (n 40) or placebo (n 40). All the women were evaluated for serum glucose, insulin, HOMA-IR (Homeostasis Model Assessment-Insulin Resistance), triglycerides, total and high density lipoprotein cholesterol, body mass index (BMI), waist circumference and blood pressure at baseline and after 12 months of treatment. Results With the exception of BMI and waist circumference, after 12 months of treatment, all the parameters studied showed a significant improvement in the myo-inositol group compared to the control group. At the end of the study, in the myo-inositol group, the number of women without metabolic syndrome was eight (20%) whereas, in the control group, only one woman no longer had the metabolic syndrome after 12 months of diet. Conclusions Myo-inositol might be considered one of the insulin-sensitizing substances in the treatment of metabolic syndrome. © 2012 International Menopause Society.
Grimaldi C.,Childrens Hospital Bambino Gesu |
Monti L.,Childrens Hospital Bambino Gesu |
Falappa P.,Childrens Hospital Bambino Gesu |
D'Ambrosio G.,Childrens Hospital Bambino Gesu |
And 2 more authors.
Journal of Pediatric Surgery | Year: 2012
Congenital intrahepatic portosystemic shunts are rare hepatic vascular anomalies that often lead to severe secondary conditions. A 6-year-old boy was referred for assessment of severe hypoxia, and a large liver mass was diagnosed with such a malformation and was managed by direct closure of the venous fistula by interventional radiology. Follow-up assessment shows normalization of the respiratory condition and a progressive reduction of the vascular liver lesion. Review of literature suggests that radiologic interventions are currently the criterion standard for managing these conditions, with surgery reserved for patients who are not eligible for radiologic procedure and those requiring liver transplantation. © 2012 Elsevier Inc.