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Biomedical subjects

A A Conti

Publications and source records attributed to A A Conti.

At least 19 recordsLinked to original sources

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↗

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↗

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↗

Obesity and nutritional behavior within a historical perspective.

Obesity is an ever increasing pathological condition in Western countries. Genetic, metabolic, social and cultural factors play different roles in the varying pictures of obesity, together with nutritional behavior. This research proposes to formulate a comparison through the literary sources of the classical world, so as to determine the modalities with which obesity and nutritional habits have been perceived in the past. In Greek and Roman art, obesity often assumed the characteristics of caricature and of satire, confirmed by the elaboration of the stereotype of the sponger. Obesity generated irony and sarcasm; meanwhile the figure of the tyrant too was modelled on the physical type of the obesus, in whom the vice both of alimentary and sexual excess was concentrated. The evaluation of obesity, in the course of the time, has seen alternate phases, that propose different physical models and elaborate different aesthetical canons, but always closely related to a strong social factor as a distinctive sign: opulence. Nowadays obesity is seen, on the contrary, as an ever increasing nutritional disorder, both in prevalence and in incidence, and, to the ideal of the fat subject, very recent years have progressively substituted a different aesthetic typology, also because hyperalimentation has been qualified as a concomitant cause for a number of degenerative disorders.

Adolescent↗

ACE DD genotype: an independent predisposition factor to venous thromboembolism.

BACKGROUND: The renin angiotensin system affects haemostasis through different mechanisms; data on the possible role of angiotensin-converting enzyme I/D polymorphism in the pathogenesis of deep venous thrombosis are conflicting, and no information is available regarding the A1166C polymorphism of the angiotensin type 1 receptor gene. In order to investigate this issue, angiotensin-converting enzyme and AT1R polymorphisms were genotyped in 336 consecutive venous thromboembolism patients and 378 controls. MATERIALS AND METHODS: Haemostasis-related risk factors have been evaluated by routine tests. Factor V Leiden, Factor II (G20210A), angiotensin-converting enzyme (I/D), and angiotensin type 1 receptor (A1166C) polymorphisms have been identified by molecular analysis. RESULTS: We documented a significant association between angiotensin-converting enzyme DD genotype and venous thromboembolism (OR=2.19 95%CI 1.51-3.17 adjusted for acquired and haemostasis-related risk factors, P<0.0001); in patients with haemostasis-related risk factors, angiotensin-converting enzyme DD genotype modified the risk of venous thromboembolism in hyperhomocysteinaemic and Factor V Leiden patients and was associated with the risk of recurrent venous thromboembolism (OR=1.83 95%CI 1.06-3.17 P=0.03). In patients without haemostasis-related risk factors the angiotensin-converting enzyme DD genotype was still an independent predictor of venous thromboembolism (OR=3.29 95%CI 2.17-4.98 adjusted for acquired risk factors, P<0.0001). No significant association between the angiotensin type 1 receptor CC genotype and venous thromboembolism was found. CONCLUSIONS: This study shows that angiotensin-converting enzyme DD genotype represents a susceptibility marker of thrombosis in subjects apparently without predisposing factors and traditional thrombophilic alterations, and increases the risk of venous thromboembolism in subjects in whom a thrombogenic condition occurs. Moreover, angiotensin-converting enzyme DD genotype may be considered a new predisposing factor to venous thromboembolism recurrence.

Adolescent↗

Relationship between the calibre of carotid arteries and the configuration of the circle of Willis in healthy older persons.

AIM: Recent papers have pointed out that the severity of brain damage that follows carotid occlusion is largely influenced by the state of integrity and functionality of the circle of Willis. In spite of this, duplex scanning investigation of carotid arteries has traditionally been focused on the assessment of the degree of the stenosis, while other features, such as the calibre of carotid arteries and their possible asymmetry, have often been neglected. The aim of the present paper was to verify, in a cohort of older persons, whether, based on the calibre of internal carotid arteries and their possible asymmetry, abnormalities of the circle of Willis can be predicted. Such information could be used to identify high risk patients in whom the status of the circle of Willis should be investigated by MR angiography. METHODS: We studied 118 healthy older persons with both duplex scanning investigation of carotid arteries and MR angiography of the circle of Willis. RESULTS: We found that the finding of abnormal internal carotid artery calibres was always associated with abnormalities of the precommunicating segments either of the anterior or of the posterior cerebral arteries. Abnormalities of communicating arteries did not affect the calibre of internal carotid arteries, but abnormalities of anterior communicating arteries could always be detected by contralateral common carotid artery compression manoeuvres. CONCLUSION: In conclusion our findings show that, in healthy older persons, duplex scanning investigation of carotid arteries may provide useful information about the integrity and functionality of the circle of Willis. Future studies should confirm our findings in patients with atherosclerotic lesions of internal carotid arteries.

Aged↗

[Appropriateness in the health system: past, present and future].

Nowadays, a health procedure or a clinical pathway are considered appropriate when they appear adequate with respect to scientific knowledge, consistent with the patient's values, safe as to risk management, and convenient with regard to the allocation of resources. This has not always been the case during the course of history, as the different clinical-methodological approaches to the same pathology in different Schools and Universities indicate, even in the same country. A hundred years ago, the difference of approaches could be explained by the limited circulation of ideas, usually based upon weak evidence, if not the personal impressions, of individual physicians. Today, on the contrary, evidence based medicine can represent a useful element in rendering homogeneous different types of behaviour in the same situation, and one of its characterising features is the elaboration of the concept of appropriateness. Appropriateness is a parameter internal to the evolution of health professions, requiring reasoned and shared employment. It originates from the need of health operators to explain why so many different kinds of behaviour exist in the context of the same clinical question. All the issues related to the concepts of clinical judgement and clinical decision-making derive from this and today more and more attention is being dedicated to the idea of appropriateness. The search for appropriateness is a progressive and cyclic process, that may always be improved. At present, strenuous team work is needed to avoid the features of the health system that are more clearly inappropriate, and that emerge from very simple analyses. Doing this is in the interest of the citizens, of health professionals and of the health economy as well.

Decision Making↗

Is the percentage of stenosis of the internal carotid artery a reliable measure of the risk of ischemic stroke? A morphometric study by duplex ultrasound of aortic arch branches in 500 normal adults.

BACKGROUND: The percentage of stenosis has been considered for the last 20 years, and still continues to be, the main criterion of choice between a surgical and a medical treatment of the atherosclerotic lesions of the aortic arch branches, particularly as regards the internal carotid artery. On the other side, it has been demonstrated that the risk of adverse acute cerebrovascular events, besides being related to the characteristics of the plaque, such as softness, subintimal haemorrhage or surface ulcer, is strictly related to the actual residual lumen of the internal carotid artery. The pre-eminent role of the percentage of stenosis in the choice of the treatment, hence, presumes a narrow range of variation of the original calibre of the vessel, yet to be proven. METHODS: Five-hundred normal adults underwent the measurement of the internal calibre of the aortic arch branches by duplex ultrasound in order to find out their actual range of variation. RESULTS: The range of variation of the internal calibre of the aortic arch branches, expressed as the ratio between the maximum and the minimum value found for each vessel, was very wide in all cases (from 180% for the right common carotid artery to 340% for the right vertebral artery). With reference to the internal carotid arteries, the range of variation was 219% for the right internal carotid artery and 241% for the left internal carotid arteries. CONCLUSIONS: Due to the wide range of variation of the original calibre of the aortic arch branches, the percentage of stenosis alone cannot be considered an accurate measure of the severity of the stenosis, and hence a reliable criterion of choice of the treatment.

Adult↗

[Diabetic nephropathy. A historical, clinical and diagnostic framework].

Diabetic nephropathy is the major chronic complication of diabetes mellitus for mortality and morbidity. It is a condition of renal damage appearing in the course of diabetes mellitus, with a clinical expression characterized by urinary signs and arterial hypertension. This condition is functionally distinguished by a progressive decrease of the glomerular filtration rate, and in the Western world it is currently the major determinant of end stage renal disease. In the last twenty years the incidence of renal failure in the course of diabetes mellitus has grown continuously, particularly in type 2 diabetic patients. The majority of patients with diabetic nephropathy reach end-stage renal failure within ten years from the first evidence of proteinuria, and, in the United States, about 30% of the chronically dyalitic patients have diabetic nephropathy. The identification and the control of the renal disease over time are based on the measurement of proteinuria. Although the most useful and reliable dosage methods for proteinuria are still debated, it appears clear today that a spot measurement of albuminuria is not a reliable indication for the diagnosis of diabetic renal disease. The measurement of albuminuria as well as of creatinuria several times a year in the diabetic subject is therefore recommended, considering also that the test needs repetition both when positive and negative. Despite of the relevant results achieved in the last few years by clinical research both in the diagnostic and in the therapeutic fields, the role of prophylactic measures still remains essential in diabetics at higher risk of nephropathy.

Albuminuria↗

Collateral circulation in internal carotid artery occlusion. A study by duplex scan and magnetic resonance angiography.

BACKGROUND: Clinical effects of internal carotid artery (ICA) occlusion may range from the absolute absence of symptoms to lethal hemispheric stroke. In this paper symptoms of patients with ICA occlusion have been related to the development of collateral circulation, different types of developed collateral circulation have been assessed, and the degree of sensitivity and specificity of duplex scan has been appraised. METHODS: Forty-eight patients with ICA occlusion or subocclusion, 24 males and 24 females, aged between 50 and 83 years (67.7+/-7.15), underwent duplex scan and magnetic resonance (MR) angiography. Nineteen patients were completely asymptomatic, 20 patients showed permanent neurological symptoms and 9 patients had shown transient symptoms. RESULTS: Twelve patients (25%) did not show any collateral circulation, 29 patients (60%) showed collateral circulation through homolateral external carotid artery branches and 7 patients (15%) showed collateral circulation through other circuits. Of the 20 patients with permanent symptoms only 8 showed collateral circulation. On the contrary, all the 19 asymptomatic patients and the 9 patients with transient symptoms showed collateral circulation. Eventually, duplex scan showed 78% sensitivity, 100%, specificity and 83% diagnostic accuracy. CONCLUSIONS: Our data show: 1) a clear-cut prevalence of collateral circulation through homolateral external carotid artery branches with respect to other possible collateral circulation; 2) an inverse relationship between the development of collateral circulation and the appearance of permanent symptoms; 3) a good diagnostic accuracy of duplex scan in revealing collateral circulation in the case of ICA occlusion.

Aged↗

The circle of Willis in healthy older persons.

BACKGROUND: The current indication for carotid surgery is based upon the percentage of stenosis of the internal carotid artery. This approach shows many limitations, one of which is to presume the anatomical completeness of the circle of Willis in all patients who are evaluated. On the contrary, there is increasing evidence of a great natural variability in the configuration of the circle of Willis. METHODS: The aim of the present paper was to investigate, by magnetic resonance angiography, the variability of the circle of Willis in a cohort of 118 healthy older persons. RESULTS: The circle of Willis showed an entirely complete configuration in 47% of the subjects, a complete configuration of its anterior part in 90% of the subjects, and a complete configuration of its posterior part in 48.5% of the subjects. CONCLUSIONS: These findings confirm the great variability of the circle of Willis even in healthy older persons and suggest that, in indicating carotid surgery, the configuration of the circle of Willis should also be taken into account.

Age Factors↗

S-100 protein and neuron-specific enolase as markers of subclinical cerebral damage after cardiac surgery: preliminary observation of a 6-month follow-up study.

Cerebral damage remains one of the hazards related to cardiac surgery with cardiopulmonary bypass. The use of biochemical markers of cerebral injury may be of practical value. We investigated the plasma release patterns of S-100 protein and neuron-specific enolase (NSE) during the intervention and their relationship with the development of neuropsychological deficits assessed 6 months after the intervention in 16 patients undergoing elective cardiac surgery with cardiopulmonary bypass. Both S-100 and NSE significantly increased peri- and postoperatively. Significant correlations were found between values measured at several time points and impaired performance in a few tests at the 6-month follow-up. A stratification into two age subgroups led to the hypothesis that age might have a confounding or a modifying effect on the association between S-100 and NSE levels, and cognitive impairment.

Aged↗

[Is evidence-based medicine really a craze? Surely it is fashionable to criticize it. A methodologic comment from the Centro Italiano per la Medicina Basata sulle Prove (Italian Center for Proof-Based Medicine)].

Evidence Based Medicine (EBM) represents the methodological search for the best solution of a clinical problem, using the most relevant scientific acquisitions of biomedical research, collected and critically appraised in the light of the experience and expertise of physicians. This search is targeted to individual patient care, in the frame of risk/benefit and cost/effectiveness ratios. EBM approach constitutes a precious tool for applied clinical practice, and can also represent a useful methodological instrument for the complete management of patients. The impetus given to outcome studies, to effectiveness studies, to careful attention for outpatients, to the individual data (of the patients of controlled trials) analysis is a major merit of EBM. Many authors nowadays consider EBM just a fashion, and today denigrating EBM appears a fashion too. Medicine complexity is enormous, and EBM can provide a useful methodological approach to this same complexity. EBM is not the automatic solution for every clinical problem, but is a logical tool for the critical evaluation of the relevance of biomedical research results and for the judgment of their applicability into daily clinical practice.

Decision Support Techniques↗

[Evidence-based guidelines for prevention and therapy of venous thromboembolism].

UNLABELLED: Recently, evidence-based guidelines for the prevention and therapy of venous thromboembolism have been published. Prophylaxis: in General Surgery patients with moderate to severe risk need to be treated with unfractioned (UFH) or low molecular weight (LMWH) heparin. Non pharmacological methods must be reserved to patients with high hemorrhagic risk and in association to heparin to patients with particularly high thromboembolic risk. In high risk Ortopedic Surgery prophylaxis with high doses LMWH or oral anticoagulants (OA) is indicated. Il Neurosurgical Surgery and in politraumatized patients prophylaxis must be individualized taking account of hemorrhagic risk; patients with acute medullary lesion with paraplegia must be treated with LMWH. In Internal Medicine conditions which determine prolonged bed rest need prophylaxis with UFH or LMWH. In pregnancy, pharmacological prophylaxis is indicated only in cases of preceding thrombotic events or documented congenital risk factors. THERAPY: deep venous thrombosis or sub-massive pulmonary embolism must be treated with anticoagulant doses of UFH or LMWH (100 U antiXa/Kg twice daily). OA must be continued for a time identifiable on the basis of underlying disease. In massive or sub-massive pulmonary embolism with hemodynamic instability thrombolysis is indicated. In heparin induced thrombocytopenia alternative antithrombotic treatments must be employed.

Administration, Oral↗

Electrophysiologic procedures and activation of the hemostatic system.

BACKGROUND: Thromboembolism occurs in 0.4% to 2% of the subjects undergoing radiofrequency ablation (RFA), but its mechanisms remain unclear. Our aim was to evaluate several parameters of the hemostatic system in relation to the electrophysiologic procedure. METHODS: Thirty consecutive patients were enrolled in the study. Fifteen underwent electrophysiologic study and 15 underwent radiofrequency ablation. Before the ablation procedure, all subjects were given an intravenous heparin bolus (2500 IU). Blood samples were drawn immediately before, at the end of, and 24 hours after the procedures. Spontaneous platelet aggregation in whole blood and in platelet-rich plasma, markers of clotting activation (prothrombin fragment 1+2 and the thrombin-antithrombin complex) and the fibrinolytic system (plasminogen activator inhibitor and D-dimer) levels were evaluated. RESULTS: At the end of the procedure, spontaneous platelet aggregation in whole blood, prothrombin fragment 1+2, thrombin-antithrombin complex, and D-dimer levels increased significantly in all patients. The hemostatic changes were more marked after RFA than after electrophysiology. Spontaneous aggregation in whole blood, prothrombin fragment 1+2, and thrombin-antithrombin complex levels at 24 hours after the procedure were similar to those observed before the procedure in both groups; D -dimer levels were still elevated with respect to preprocedure levels, with a trend toward higher levels in patients undergoing RFA rather than electrophysiology. A significantly more marked activation of coagulation (prothrombin fragment 1+2, P <.005) was found in patients in whom the mean duration of energy application was higher than 23.5 seconds. CONCLUSIONS: Our data suggest that antithrombotic prevention with a prolonged administration of heparin and/or the association of antiplatelet agents should be considered in patients undergoing RFA.

Adult↗