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Biomedical subjects

G F Gensini

Publications and source records attributed to G F Gensini.

At least 19 recordsLinked to original sources
PubMed2006

Effect of individualizing starting doses of a statin according to baseline LDL-cholesterol levels on achieving cholesterol targets: the achieve cholesterol targets fast with atorvastatin stratified titration (ACTFAST) study.

AIMS: To investigate whether selecting the starting dose of atorvastatin according to baseline and target (<2.6 mmol/L) LDL-cholesterol (LDL-C) values would allow high-risk subjects to achieve target LDL-C concentration within 12 weeks, with the initial dose or a single uptitration. METHODS AND RESULTS: Twelve-week, prospective, open-label trial that enrolled 2117 high-risk subjects (statin-free [SF] or statin-treated [ST]). Subjects with LDL-C >2.6 mmol/L (100mg/dL) but <or=5.7 mmol/L (220 mg/dL) were assigned a starting dose of atorvastatin (10, 20, 40 or 80 mg/day) based on LDL-C and status of statin use at baseline, with a single uptitration at 6 weeks, if required. There was no washout for ST subjects. At study end, 80% of SF (82%, 82%, 83% and 72% with 10, 20, 40 and 80 mg, respectively) and 59% of ST (60%, 61% and 51% with 20, 40 and 80 mg, respectively) subjects reached LDL-C target. In the ST group, an additional 21-41% reduction in LDL-C was observed over the statin used at baseline. Atorvastatin was well tolerated. CONCLUSION: This study confirms that individualizing the starting dose of atorvastatin according to baseline and target LDL-C values (i.e. the required LDL-C reduction), allows a large majority of high-risk subjects to achieve target safely, within 12 weeks, with the initial dose or with a single titration.

Aged↗
PubMed2006

Italian SPREAD Guidelines: from past to future.

The development of the Italian Guidelines on Stroke involved a multidisciplinary working group, named the "SPREAD Collaboration" (Stroke PREvention and Awareness Diffusion), composed at present of different professional organisations and two patients' associations. The group was organised into operative subcommittees. Each subcommittee dealt with a different area covered by the guidelines and was composed of 5-10 experts in the specific field. A "scientific task force" and an editorial board were responsible for coordinating and reviewing the texts progressively processed and produced.

Forecasting↗
PubMed2006

The Stroke in Italy and Related Impact on Outcome (SIRIO) study: design and baseline data.

The SIRIO study collected detailed information on the stroke care of patients treated in neurological departments in Italy. This report refers to the baseline profile of patients. Each centre recorded the incident cases of ischaemic and haemorrhagic stroke, excluding SAH, for 1-4 months. Baseline data include demographics, risk factors, comorbidities, pre-event medications, social conditions, NIHSS and Rankin scale on entry, Barthel Index pre-event, diagnostic tests and treatments applied on entry. Overall, 3018 patients (56.7% men; mean age 72.1+/-12.2 years) with ischaemic (85.3%) or haemorrhagic stroke were hospitalised in 103 centres; 51% arrived by ambulance. Median time to hospital was 140 min (RIQ: 60-615). TOAST classification of the 2573 ischaemic strokes was: 29.4% large-artery atherosclerosis, 24.6% cardioembolic, 26.2% small vessels occlusion, 6.5% other determined causes and 13.3% undetermined. CT and/or MR were performed in all patients. Total Greenfield's comorbidity score was 5.4+/-3.5. Mean Barthel Index pre-event was 93+/-17; Rankin score on entry was 4-5 in 48% of the patients and 0-1 in 25%. Mean NIHSS on entry was 7.1+/-5.4; 52% of the patients had a NHISS <6 and 1% >22. SIRIO began giving the expected insights on the in-hospital management of stroke in Italy. Further information will be provided by the longitudinal phase of the study, which is in progress. Pre-event patient management and mode of reporting call for additional educational actions.

Age Factors↗
PubMed2006

Alpha-linolenic acid and cardiovascular diseases omega-3 fatty acids beyond eicosapentaenoic acid and docosahexaenoic acid.

Over the last decades, an increasing body of evidence has been accumulated on the beneficial effect of polyunsaturated fatty acids both in primary and secondary prevention of cardiovascular diseases. However, the vast majority of the studies has been performed on long-chain polyunsaturated fatty acids, such as docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) and not on their biochemical precursor, alpha-linolenic acid (ALA). Actually, ALA has some other beneficial effects apart from the known antiarrhythmic effect. In fact, ALA has a strong inhibitory effect on omega-6 metabolic pathway. An adequate daily intake of ALA shifts metabolic pathway to EPA, so favoring the formation of products with a predominant antiaggregating and vasorelaxing action, with respect to eicosanoids with a predominant thrombotic effect. Some important evidences have been raised on the association between ALA and cardiovascular mortality. Indeed, dietary ALA has been associated with a lower rate of fatal and nonfatal coronary events. Hence, major scientific associations published nutritional guidelines including a specific recommendation for ALA.

Cardiovascular Diseases↗
PubMed2006

The concept of normality through history: a didactic review of features related to philosophy, statistics and medicine.

Normality characterises in medicine any possible qualitative or quantitative situation whose absence implies an illness or a state of abnormality. The illness concept was first a philosophical one. But the use of mathematics in the study of biological events, which began with Galton (1822-1911) and with Pearson (1857-1936), changed the frame of reference. In the second part of the 19th century mathematics was used to study the distribution of some biological characteristics in the evolution of the species. Around 1900, statistics became the basis for the study of the diffusion of the illnesses. Half a century later statistics made possible the transition from the description of single cases to groups of cases. Even more important is the concept of "normality" in laboratory medicine. In this field the search for the "perfect norm" was, and possibly still is, under way. The widespread use of statistics in the laboratory has allowed the definition, in a certain sense, of a new normality. This is the reason why the term "reference value" has been introduced. However, even the introduction of this new term has merely shifted the problem, and not resolved it.

Biology↗
PubMed2006

Role of natriuretic peptides in heart failure patients with special reference to those on cardiac resynchronization therapy.

In recent years natriuretic peptides (NPs) have emerged as important tools for evaluation of heart failure patients. Since its approval by the Food and Drug Administration (FDA) in November 2000, recent surveys suggest that approximately 83% of hospitals in the US use some type of NP testing. Although NP testing was originally focused on rapid diagnosis of patients presenting to the emergency department with shortness of breath, clinicians regularly look to NPs for diagnosing minimally symptomatic or asymptomatic left ventricular dysfunction, and using NPs levels in clinic to help ascertain when decompensation is present. NP testing is now included in the guidelines for the diagnosis and treatment of chronic heart failure and in the Italian Consensus Document for the clinical use of NPs. Recommendations indicate that assessment of NPs can be considered a reliable rule-out test of heart failure in primary care and in the emergency room even if they stated that the role for treatment monitoring or for prognostic evaluation needs to be determined. In recent years, cardiac resynchronization therapy (CRT) was introduced as a new treatment modality for patients with systolic heart failure and several studies suggest that plasma concentration of NPs ensues as a very useful parameter for evaluating and monitoring patients who undergo CRT. Thus this article aims not only to summarise data concerning NPs measurement in patients with heart failure, but also to indicate how these markers could be utilized in the future to objectively assess effects of CRT (identification of responders). In conclusion, if further studies will confirm above mentioned remarks, it would be possible that NPs evaluation can help to tailor the more suitable therapy for each heart failure patient and, therefore, to reduce the number of failures.

Arrhythmias, Cardiac↗
PubMed2005

Protein Z plasma levels in different phases of activity of coronary atherosclerosis.

We previously reported that low protein Z plasma levels are associated with acute coronary syndromes (ACS). Aim of the present study was to evaluate protein Z levels in different phases of activity of coronary atherosclerosis. Protein Z plasma levels were measured in 166 (131 male and 35 female) patients consecutively admitted to the University of Florence with a diagnosis of ACS (group A), 166 (131 male and 35 female) patients selected by age and gender in relation to group A from those with a clinical history of ACS who remained symptom- and/or event-free over the last year before the investigation (group B); and 332 (262 male and 70 female) controls comparable for age and gender with the other two groups. None had liver or renal dysfunction nor showed a positivity for antiphospholipid antibodies or for factor V Leiden mutation. Patients under warfarin therapy were excluded. Mean protein Z plasma levels were found to be significantly (P < 0.0001) lower in group A (1475 +/- 684.1 ng mL(-1)) and group B (1327.6 +/- 690.7 ng mL(-1)) as compared with control group (1650.1 +/- 634.5 ng mL(-1)), while no significant differences existed between the two groups of patients (P = 0.06). A logistic regression analysis, performed after the division of the study population into quartiles of protein Z levels and adjusted for all possible confounders, showed a significant increased risk of ACS for the lowest (<1213 ng mL(-1)) as compared with the highest quartile of protein Z in both groups of patients [group A odds ratio (OR): 2.7, 95% CI 1.3-5.5, P = 0.007; group B OR: 3.2, 95% CI 1.1-8.9, P = 0.02). In conclusion, these results strengthen our previous data on low protein Z plasma levels in ACS and indicate a possible dose-response effect of decreasing protein Z plasma levels on the coronary atherosclerotic disease.

Adult↗
PubMed2005

PAI-1 and homocysteine, but not lipoprotein (a) and thrombophilic polymorphisms, are independently associated with the occurrence of major adverse cardiac events after successful coronary stenting.

OBJECTIVE: To evaluate the role of factor V Leiden, prothrombin G20210A polymorphism, plasminogen activator inhibitor type 1 (PAI-1) 4G/5G polymorphism, PAI-1, homocysteine, and lipoprotein (a) (Lp(a)) in the occurrence of major adverse cardiac events (MACE) in patients with acute coronary syndromes who underwent coronary stenting. DESIGN: 520 patients (375 men and 145 women) with acute coronary syndromes and 520 age and sex matched controls were enrolled. MACE were recorded for 109 patients. Heterozygosity for factor V Leiden, prothrombin G20210A polymorphism, and 4G/5G polymorphism did not significantly differ between patients with and without MACE. A significantly higher percentage of patients with increased homocysteine (28% v 19%, p < 0.001) and PAI-1 concentrations (25% v 16%, p < 0.001) had MACE with respect to those who did not. In Kaplan-Meier survival analysis, the overall risk of MACE was significantly higher among patients with increased PAI-1 (p = 0.006) and homocysteine concentrations (p = 0.04). Cox regression analysis adjusted for age, sex, traditional cardiovascular risk factors, renal function, systolic left ventricular function, the number of stenosed vessels, and history of percutaneous coronary intervention or coronary artery bypass grafting showed that homocysteine (odds ratio 7.5, 95% confidence interval (CI) 1.1 to 57.7, p < 0.05) and PAI-1 concentrations (odds ratio 5.3, 95% CI 1.2 to 23.8, p < 0.05) within the fifth quintile (with respect to the first) were significant and independent risk factors for the future occurrence of MACE. CONCLUSIONS: Increased PAI-1 and homocysteine concentrations are independent risk factors for MACE after successful coronary stenting, whereas Lp(a) and thrombophilic polymorphisms are not predictive.

Adult↗
PubMed2005

ACE DD genotype: a predisposing factor for abdominal aortic aneurysm.

OBJECTIVE: To examine the role of polymorphisms in angiotensin converting enzyme (ACE, I/D) and angiotensin II receptor (AT1R, A1166C) in the development of abdominal aortic aneurysm (AAA). MATERIALS AND METHODS: We investigated 250 consecutive patients, 217 males and 33 females (median age 72, range 50-83), undergone AAA elective repair and 250 healthy controls, comparable for sex and age. ACE and AT1R polymorphisms were studied by PCR-RFLP analysis. The genotype distribution was in Hardy-Weinberg equilibrium for all polymorphisms. RESULTS: The genotype distribution and allele frequency of ACE I/D, but not AT1R A1166C polymorphism were significantly different between patients and controls (ACE I/D: p=0.0002 and p<0.0001, respectively, and AT1R A1166C: p=0.6 and p=0.4, respectively). An association between the ACE DD genotype and the predisposition to AAA was found (OR DD vs. ID+II=1.9 95% CI 1.3-2.9, p<0.0001). Multivariate analysis adjusted for age, sex, traditional vascular risk factors and other atherosclerotic localizations, showed ACE DD genotype to be independently related to the disease (OR DD vs. ID+II=2.4, 95% CI 1.3-4.2 p=0.003). CONCLUSIONS: Our findings document that ACE DD genotype represents a susceptibility factor for AAA.

Aged↗
PubMed2005

Dietary habits, lifestyle and cardiovascular risk factors in a clinically healthy Italian population: the 'Florence' diet is not Mediterranean.

OBJECTIVE: To evaluate dietary habits and lifestyle of Italian subjects, to provide current data on adequacy of the nutritional guidelines and recommendations especially in relation to primary prevention of cardiovascular diseases and to assess the influence of dietary habits on lipid profile and homocysteine levels. DESIGN: Cross-sectional. SETTING: Population-based study. SUBJECTS: A sample of 520 clinically healthy subjects (211 males, 309 females) with a mean age of 46 y, living in Florence area, Italy. INTERVENTIONS: Dietary pattern was assessed by trained dietitians through a semiquantitative food questionnaire. Fasting blood samples were drawn for assessment of lipid profile, homocysteine and circulating vitamins. RESULTS: Contribution from total fats was over 30% in about 70% of subjects and intake of saturated fatty acids (SFA) was above the recommended values in at least 40% of the study population. Furthermore, almost the whole (99.6%) population reported low intake of polyunsaturated fatty acids (PUFA). High levels of total cholesterol were present in over 40% of the study population, whereas abnormal values of LDL-cholesterol were observed in about 30%. High levels of homocysteine were found in 11.7% of the study population. An extremely high percentage of subjects reported low intake of vitamins, especially with regard to folic acid (89%), vitamin B(6) (70.1%) and vitamin E (99.6%). In a multiple linear regression model, circulating levels of vitamin B(12) and folic acid, and intake of alcohol and vitamin C resulted in being independently associated with homocysteine plasma levels. CONCLUSIONS: In a typical Mediterranean country, general outlines of Mediterranean diet are not completely followed, especially concerning total fats, SFA, PUFA and vitamins' intake. SPONSORSHIP: Ministero della Salute (Italy) - 'Progetto per la Salute e la Prevenzione di Malattia' 2001-2003.

Cardiovascular Diseases↗
PubMed2005

Relevance of post-methionine homocysteine and lipoprotein (a) in evaluating the cardiovascular risk in young CAD patients.

BACKGROUND: Aims of our study were to evaluate the prevalence of high lipoprotein (a) [Lp(a)] and homocysteine levels - both in the fasting state (FHcy) and post-methionine (PMHcy) - in young coronary artery disease (CAD) patients, and to investigate the role of genetic and environmental factors for hyperhomocysteinaemia. MATERIALS AND METHODS: We studied 140 patients with angiographically documented CAD (24 women </= 55 years and 116 men </= 50 years) and 140 healthy subjects as controls. RESULTS: Both FHcy [13.2 (5.4-45.8) vs. 9.0 (5.1-24) micromol L(-1)); P < 0.0001] and PMHcy [(39.4 (9.0-66.4) vs. 25.2 (16.4-33.9); P < 0.0001] were significantly higher in patients than in controls. Lp(a) levels were significantly higher in patients than in controls (200 (3-1486) mg L(-1) vs. 97 (10-412) mg L(-1); P < 0.0001). At the multivariate analysis, adjusted for the classical cardiovascular risk factors and creatinine levels, the OR (95% CI) for CAD at young age significantly increased in the fourth quartile of the distribution of FHcy, PMHcy and Lp(a) levels [FHcy: 14.9 (4.1-58), P < 0.0001; PMHcy: 19.2 (4.0-86.3); P < 0.0001; Lp(a): 19.6 (4.7-78.6): < 0.0001]. Vitamin deficiencies were detected in 28/140 (20%) patients. The prevalence of the homozygous C677T (+/+) methylenetetrahydrofolatereductase genotype was higher, but not significantly different, in patients (22.8%) than in controls (18.6%). The allele frequency of the 844ins68 insertion variant in the cystathionine beta-synthase gene was 0.08 in the control group and 0.06 in the patient group. CONCLUSIONS: Results of the present study indicate the usefulness of including fasting and post-methionine Hcy, and Lp(a) determination in the diagnostic panels of young CAD patients, in order to obtain a better assessment of their cardiovascular risk profile.

Adult↗
PubMed2005

Thrombophilic risk factors in patients with severe carotid atherosclerosis.

Carotid stenosis and atrial fibrillation are the strongest risk factors for ischemic stroke. Ongoing prevention efforts include the identification of novel factors that increase the risk for carotid atherosclerosis. The aim of this study was to determine the thrombophilic risk profile of patients with severe carotid stenosis by evaluating a number of genetic and metabolic risk factors [factor (F)II G20210A, factor V Leiden, MTHFR C677T polymorphisms, anticardiolipin antibodies (aCL), lipoprotein(a) (Lp(a)), and homocysteine (Hcy)]. The study population consisted of 615 patients [(410 M/205 F; median age 73 (26-94) years] with severe (> 70%) carotid stenosis, and 615 apparently healthy subjects [(410 M/205 F; age 73 (31-92) years]. On multivariate analysis, independent risk factors were elevated Hcy [odds ratio (OR) 7.6, 95% confidence interval (CI) 4.8, 11.8] and Lp(a) levels (OR 2.9, 95% CI 2.1, 3.9), the presence of aCL (OR 5.7, 95% CI 3.1, 10.4) and heterozygosity for FII G20210A polymorphism (OR 2.8, 95% CI 1.3, 5.9). In the subgroup of women, independent risk factors for severe carotid atherosclerosis were: high levels of Hcy and Lp(a) and the presence of aCL, whereas hyperhomocysteinemia, elevated Lp(a) levels, aCL, FII G20210A and MTHFR 677TT polymorphisms remained independent risk factors in the subgroup of men. The results of the present study demonstrate that the prevalence of the thrombophilic risk factors is increased in patients with severe carotid atherosclerosis.

Adult↗
PubMed2005

Past and present of ''what will please the lord'': an updated history of the concept of placebo.

In ecclesiastic tradition the term ''Placebo'' indicated the promise to please the Lord in medieval prayer. The expression ''Placebo Domino'' (''I shall please the Lord'') constituted the beginning of a famous passage of a V century A.D. translation of the Bible. It was in the second half of the XVIII century that the word Placebo became an integral part of the medical-pharmacological vocabulary, and in fact Quincy's Lexicon (1787) defined it as a remedy used more to please than to heal people. For centuries placebos have been considered precious deceptive therapies and, until 1945, they were generally considered to be morally useful management tools. At the end of World War II it was clear that a critical evaluation of the function of placebos was needed to shed some light on their real role. Following this methodological call, in the years following different studies on placebos were proposed, and in 1955 HK Beecher published in the JAMA a paper, ''The Powerful Placebo'', in which he concluded that it was evident that placebos had a high degree of therapeutic effectiveness. Recent evidence points to the fact that, on the contrary, placebos do not have major clinical effects and that the limits of their application should be fully acknowledged.

History, 18th Century↗
PubMed2004

Influence of eNOS gene polymorphisms on carotid atherosclerosis.

INTRODUCTION: Nitric oxide (NO) is an endothelium-derived relaxing factor which plays a role in atherogenetic events. Polymorphisms in the endothelial NO synthase gene (eNOS) influences the functional activity of the enzyme and affect the susceptibility to atherogenesis. In this study we determined whether T-786C, G894T and 4a/4b eNOS genetic variants may increase the susceptibility to carotid atherosclerosis. METHODS: The study groups included 304 consecutive patients with severe carotid stenosis (>/=70%) and 544 control subjects. The eNOS polymorphisms were analysed by molecular biology techniques. RESULTS: The genotype distribution and allele frequency of eNOS 4a/4b, but not T-786C and G894T, polymorphism was significantly different between patients and controls. Using logistic regression with adjustment for other risk factors, the 4a allele and the combined genotype 4a4a+4a4b/894TT+GT and -786CC+TC/894TT+GT were associated with carotid stenosis (OR=1.5, p=0.02; OR=1.8, p=0.01; OR=1.5, p=0.04, respectively). In a subset of patients (30 of 304) with no traditional risk factors for atherosclerosis, a relatively high incidence of the 4a allele and 4a4a+4a4b/-786CC+TC combined genotype was noted. DISCUSSION: Our findings suggest that the 4a allele and the eNOS combined genotypes are independent predisposing factors to carotid atherosclerosis.

Adult↗
PubMed2004

Cytokine gene expression and production by human LPS-stimulated mononuclear cells are inhibited by sulfated heparin-like semi-synthetic derivatives.

BACKGROUND: The K5 polysaccharide obtained from Escherichia coli strain 010:K5:H4 is a polymer of the disaccharidic unit formed by D-glucuronic acid and N-acetylglucosamine. This structure is akin to N-acetylheparosan, the precursory polymer of heparin and of heparan sulfate. This structural affinity with N-acetylated heparin and with de-sulfated heparin makes the K5 polysaccharide extremely useful for the preparation of sulfated heparin-like semi-synthetic derivatives. It has been demonstrated that heparins are able to inhibit tissue factor and cytokine production and expression by human monocytes. OBJECTIVE: The aim of this study was to evaluate the effects of four different heparin-like semi-synthetic derivatives on inflammatory cytokine production and expression by human mononuclear cells. RESULTS: The simultaneous addition of lipopolysaccharide (LPS; 0.2 and 10 micro g mL(-1)) and the K5 polysaccharide did not inhibit interleukin (IL)-1beta, IL-6 or tumor necrosis factor (TNF)-alpha production by stimulated mononuclear cells. IL-1beta, IL-6 and TNF-alpha concentrations in supernatants of LPS-stimulated mononuclear cells were not influenced by the addition of N,O-sulfated K5 polysaccharide (K5-N, OS) and epimerized N-sulfated K5 polysaccharide (K5 NS epi) at 5 and 10 microg mL(-1), whereas the addition of epimerized N,O-sulfated K5 polysaccharide (K5-N, OS epi) (5 and 10 microg mL(-1)) and O-sulfated K5 polysaccharide (K5-OS) (5 and 10 microg mL(-1)) to LPS-stimulated cells caused a significant dose-dependent inhibition of IL-1beta, IL-6 and TNF-alpha. All sulfated heparin-like semi-synthetic derivatives did not influence the IL-10 production by LPS-stimulated mononuclear cells. In LPS-stimulated cells (0.2 and 10 microg mL(-1)), K5-OS or K5-N, OS epi at 5 and 10 microg mL(-1) markedly decreased TNF-alpha mRNA expression. CONCLUSIONS: These results indicate that the sulfated heparin-like semi-synthetic derivatives K5-OS and K5-N, OS epi are able to inhibit both expression and production of inflammatory cytokines, whereas they do not influence the anti-inflammatory cytokine IL-10, suggesting a potential role for these products as modulators of inflammatory reactions.

Bacterial Capsules↗
PubMed2004

The evaluation of the results of clinical trials: surrogate end points and composite end points.

The evaluation of the clinical outcome of patients enrolled in randomised controlled studies should always be accurate and objective. The methods used to assess and report patients' results must consequently be indicated a priori in the design of the clinical experimentation. Major (hard) individual end points currently constitute the gold standard in the definition of outcome measures, yet surrogate and composite end points are spreading diffusely as alternative/complementary outcome measures. Surrogate end points are minor outcome measures that are easier to record and are being adopted instead of major end points. They may be considered acceptable substitutes of hard end points when capable of predicting major events reliably, and when it may be demonstrated that the intervention on such surrogate end points consistently modifies the incidence of the event. In other cases they cannot represent predictive elements of major clinical outcomes. Composite (combined) primary end points may contribute to improve the statistical precision of a clinical trial; moreover, since clinical trials are particularly expensive, their identification permits more limited samples of patients to be enrolled. Their limits include the possibility that the direction in which the different outcome measures composing the combined end point are modified is not the same. Biomedical researchers are called upon to design studies adopting major (hard) end points, rather than solitary surrogate end points, in order to provide really useful information for the care of patients. The selection of composite end points requires notable methodological attention so as to retrieve the most reliable estimates on the efficacy and the effectiveness of treatments.

Humans↗