Changes over time in the prevalence and quality of care of type 2 diabetes in Italy: the Casale Monferrato surveys, 1988 and 2000

Background and aimsIn this study we assessed the prevalence of diagnosed type 2 diabetes and the quality of care during the period 1988–2000 in an Italian population.Methods and resultsTwo population-based surveys, using similar methods and centralized measurements, were conducted in 1988 and 2000 in a representative Italian area to identify people with known diabetes. The adjusted prevalence (reference, 2001 Italian population) was computed. The age- and sex-adjusted prevalence rates of diabetes in the population of Casale Monferrato were 2.13% (2.05–2.22) in 1988 and 3.07% (2.97–3.17) in 2000. In comparison with diabetic persons recruited in 1988 and independently of age and sex, persons recruited in 2000 had a lower likelihood of having HbA1c ≥7.0% (OR = 0.48; 0.42–0.56), diastolic blood pressure ≥80 mmHg (OR = 0.61; 0.49–0.75), LDL cholesterol ≥2.59 mmol/l (OR = 0.77; 0.63–0.93) and AER ≥20 μg/min (OR = 0.53; 0.45–0.61; they had a higher likelihood of having BMI ≥25 kg/m² (OR = 1.49; 1.2–1.74). However, 45.4% of patients still had HbA1c ≥7.0%, 80% blood pressure ≥130/80 mmHg and 79% LDL-cholesterol values ≥2.59 mmol/l.ConclusionMore than two-thirds of Italians with diabetes are now aged 65 years and more. The quality of control of glycemia, lipids and blood pressure improved and the prevalence of diabetic nephropathy decreased over time, although complete adherence to international guidelines has not yet been achieved.     

Impact of reperfusion strategies on in-hospital outcome in ST-elevation myocardial infarction in a context of interhospital network: data from the prospective VENERE registry (VENEto acute myocardial infarction REgistry]

BACKGROUND: Primary angioplasty (pPCI) is the most effective reperfusion treatment of acute ST-elevation myocardial infarction (STEMI), but logistic- and organization-related problems could affect the outcome. The aim of this study was to investigate the in-hospital outcome according to reperfusion strategy in the Veneto Region cardiology network. METHODS: A treatment protocol, aimed to treat patients with high-risk STEMI by pPCI on-site or after transport, was developed and shared by the majority of cardiology departments in the Veneto Region. Data of all consecutive patients with STEMI were prospectively recorded during a 6-month period. RESULTS: 999 patients with symptom onset < 12 hours were admitted to the 28 participating hospitals: 860 were treated on-site and 139 were transferred from the admitting hospital to an interventional center for PCI. Overall, 82% of patients were treated with reperfusion therapy. Ten patients died immediately before any treatment could be initiated. In 170 patients who did not receive any reperfusion treatment, in 302 patients who received fibrinolysis (and eventually rescue PCI) and in 517 patients sent to pPCI, the following in-hospital outcome was observed respectively: mortality rate 10, 6.95 and 6.57%; reinfarction rate 0.6, 1 and 0.4%; incidence of stroke 1.7, 1.4 and 0.9%; the need for urgent revascularization procedure 6.5, 10 and 2.3%. After adjustment for confounding variables, the in-hospital occurrence of the combined events was significantly lower in patients treated with pP-CI (odds ratio 0.33, confidence interval 0.20-0.53, p < 0.01) as well as a trend for a reduced in-hospital mortality was observed (odds ratio 0.51, confidence interval 0.26-1.03, p = 0.06). CONCLUSIONS: In the VENERE registry, patients treated with pPCI had a better in-hospital outcome as compared to those treated with fibrinolytic strategy.     

Asymptomatic cardiac lymphoma in a hepatitis C virus-positive thalassemic patient.

Primary cardiac non-Hodgkin lymphomas are fast-growing intracavitary and/or intramyocardial nodular masses, while secondary lymphomas most commonly infiltrate the cardiac tissue. By any definition, cardiac non-Hodgkin lymphomas usually manifest through arrhythmias, refractory heart failure, pericardial effusion, and embolic stroke. We here describe a case of a cardiac non-Hodgkin lymphoma in which the following, previously undescribed features manifest simultaneously. It occurred in a polytransfused hepatitis C virus-positive splenectomized thalassemic patient; it rapidly grew, giving rise to an enormous right atrial mass and, this notwithstanding, it was completely asymptomatic. This cardiac lymphoma was discovered during staging for a CD20+ large B-cell lymphoma of the tonsils. In particular, transesophageal echocardiography, showing that this prolapsing mass had a wide base on the atrial wall, led us to strongly suspect the lymphomatous origin of the mass itself. Notwithstanding anti-CD20 antibody therapy, urgent surgery was unavoidable and histology revealed that the mass consisted of lymphoma proliferation infiltrating even the right atrial wall and the pericardium. During the postoperative course the patient presented with a massive, fatal hemopericardium consequent to intravascular disseminated coagulation. This very unusual case, occurring in a hepatitis C virus-positive thalassemic patient, suggests that a case control study on the incidence of non-Hodgkin lymphoma in such patients may be interesting.     

Interleukin 3 enhances the cytotoxic activity of 1-β-d-arabinofuranosylcytosine (ara-C) on acute myeloblastic leukaemia (AML) cells

We have evaluated the possibility of enhancing the cell killing effect of ara-C on AML blasts by increasing their proliferative activity with haemopoietic growth factors. Leukaemic cells from 10 AML patients were incubated for 3 d in liquid culture in the presence or in the absence of the human recombinant growth factors IL-1 beta (5 U/ml) and IL-3 (3 U/ml), and subsequently exposed to ara-C (3 micrograms/ml) for the last 24 h. The number of residual leukaemic stem cells was evaluated by a clonogenic assay in semisolid medium. The results showed that ara-C exposure inhibits the proliferation of a higher proportion of clonogenic cells in cultures pretreated with growth factors than in the controls (mean inhibitory values: in the absence of growth factors = 49.8%; with IL-1 beta = 58.3%; with IL-3 78.9%). The effect was statistically significant only when IL-3 was used as a growth factor. The results suggest that haemopoietic growth factors may help to improve the therapeutic index of cytostatic agents.     

Anterior myocardial infarction in a chronic alcoholic man on disulfiram therapy: a case report]

Disulfiram is a drug used since 1940 in the treatment of alcohol dependence. However, it is not a completely safe drug; there are in the literature some case reports of more severe reaction than the usual "acetaldehyde syndrome" secondary to ingestion of disulfiram and alcohol. We describe a case of a 45-year-old, chronic alcoholic man in treatment with disulfiram, who suffered an acute anterior myocardial infarction, successfully treated with thrombolysis. The possible factors precipitating acute myocardial infarction in this patient are discussed.     

Associations between γ-glutamyl transferase, metabolic abnormalities and inflammation in healthy subjects from a population-based cohort: A possible implication for oxidative stress

AIM: To examine the relationships between γ -glutamyltransferase (GGT), alanine-aminotransferase (ALT),aspartate-aminotransferase (AST) and various metabolic parameters, C-reactive protein (CRP) and an oxidative stress marker (nitrotyrosine, NT) in subjects without any metabolic abnormalities from a population-based sample.METHODS: Two hundred and five subjects with normal body mass index (BMI), glucose tolerance, and without any metabolic abnormality were studied out of 1339subjects, without known liver diseases, alcohol abuse or use of hepatotoxic drugs, who are representative of the 45-64 aged population of Asti (north-western Italy).RESULTS: In all patients metabolic parameters and hs-CRP levels linearly increase from the lowest to the highest ALT and GGT tertiles, while in subjects without metabolic abnormalities, there is a significant association between fasting glucose, uric acid, waist circumference,hs-CRP, triglyceride values, and GGT levels. In these subjects, male sex, higher hs-CRP and glucose levels are associated with GGT levels in a multiple regression model, after adjustments for multiple confounders.In the same model, median NT levels are significantly associated with the increasing GGT tertile (β = 1.06;95%CI 0.67-1.45), but not with the AST and ALT tertiles.In a multiple regression model, after adjusting for age,sex, BMI, waist, smoking, and alcohol consumption, both NT (β = 0.05; 95%CI 0.02-0.08) and hs-CRP levels (β =0.09; 95%CI 0.03-0.15) are significantly associated with fasting glycemia.CONCLUSION: GGT, an easy, universally standardized and available measurement, could represent an early marker of sub-clinical inflammation and oxidative stress in otherwise healthy individuals. Prospective studies are needed to establish if GGT could predict future diabetes in these subjects.     

Transarterial chemoembolization (TACE) for unresectable hepatocellular carcinoma in cirrhotics: functional hepatic reserve and survival

BACKGROUND/AIMS: Transarterial chemoembolization is widely used for palliative treatment of hepatocellular carcinoma, but patient's characteristics associated with maximal benefit are still undefined. METHODOLOGY: In 81 cirrhotic patients with unresectable hepatocellular carcinoma, who underwent transarterial chemoembolization, variables correlated with survival were studied. In 46/81, the antipyrine metabolism test has been performed before and 72 hours after first transarterial chemoembolization. RESULTS: Mean overall survival of whole population was 22 months. One-, two-, and three-year survival rates were respectively 85%, 38.6%, and 18.1%. Better survival was observed in those patients who received more than one treatment (p = 0.016), while no relationship was found with treatment response, drug used, or number of lobes involved. Univariate analysis of the subgroup with antipyrine pharmacokinetic data revealed a significant relation between survival and baseline albumin (p = 0.039), total cholesterol (p = 0.036), AST (p = 0.017), log of total bilirubin (p = 0.017), and Child-Pugh class (p = 0.029), but not with parameters of antipyrine metabolism. Antipyrine metabolism was not significantly modified by transarterial chemoembolization in the subgroup tested before and after the first treatment. Using Cox regression analysis and selecting AST and log of total bilirubin, a prognostic index was defined: prognostic index 0.006 (AST-83.044) + 0.638 [log of total bilirubin-0.1175]. One-, two-, and three-year survival rates were respectively 92%, 59.2%, and 29.6% for the patient group with prognostic index < 0, and 76%, 14.3%, and 4.8% for the group with prognostic index > 0 (p < 0.01). CONCLUSIONS: Transarterial chemoembolization is a safe procedure and appears beneficial for those patients with a good functional hepatic reserve. The antipyrine metabolism test does not provide any additional prognostic information.     

Evidence for a direct and non-receptor-mediated action of 5HT2 antagonists on transmembrane cation transport systems

Summary Changes in transmembrane sodium fluxes have been reported in normotensive and in hypertensive subjects after ketanserin administration. In this study, the effects of the serotonergic system on transmembrane sodium transport mechanisms have been investigated in vitro. In erythrocytes drawn from ten healthy subjects, we studied the effects of serotonin (5HT) on the Na/K pump, Na/K cotransport, Na/Li countertransport, and passive permeability of Na. No significant changes were found. A direct, non-receptor-mediated action of ketanserin was then suspected, and the effects of two concentrations of ketanserin (5×10^-8 and 5×10^-7 M) were evaluated in erythrocytes from 12 normal volunteers. Both concentrations of ketanserin significantly decreased the activity of the Na/K pump and increased the activity of Na/Li countertransport. Na/K cotransport and passive permeability were not affected. Indirect evidence of the action of ketanserin on sodium transmembrane fluxes came from other experiments. In the red blood cells taken from five normal subjects and incubated for 2 hours in a plasma pool, we evaluated the changes in intracellular sodium concentration induced by the presence of 5HT or ketanserin. A significant decrease in intracellular sodium concentration occurred only with ketanserin. This study indicates that ketanserin has a direct influence on transmembrane sodium fluxes. If this action were also present in other cells, it might contribute to the actions of the drug at vascular, nervous, and renal tubular levels.     

Inhibition of vascular endothelial growth factor receptor 2-mediated endothelial cell activation by Axl tyrosine kinase receptor

GAS6, the product of a growth arrest specific (GAS) gene, is the ligand of the tyrosine kinase receptor Axl. GAS6 and Axl are both expressed in endothelial cells, where they are involved in many processes such as leukocyte transmigration through capillaries and neointima formation in injured vessels. Here, we show that Axl stimulation by GAS6 results in inhibition of the ligand-dependent activation of vascular endothelial growth factor (VEGF) receptor 2 and the consequent activation of an angiogenic program in vascular endothelial cells. GAS6 inhibits chemotaxis of endothelial cells stimulated by VEGF-A isoforms, but not that triggered by fibroblast growth factor-2 or hepatocyte growth factor. Furthermore, it inhibits endothelial cell morphogenesis on Matrigel and VEGF-A-dependent vascularization of chick chorion allantoid membrane. GAS6 activates the tyrosine phosphatase SHP-2 (SH2 domain-containing tyrosine phosphatase 2), which is instrumental in the negative feedback exerted by Axl on VEGF-A activities. A dominant-negative SHP-2 mutant, in which Cys 459 is substituted by Ser, reverted the effect of GAS6 on stimulation of VEGF receptor 2 and endothelial chemotaxis triggered by VEGF-A. These studies provide the first demonstration of a cross talk between Axl and VEGF receptor 2 and add new information on the regulation of VEGF-A activities during tissue vascularization.