An innovative, easily fabricated, silver nanoparticle-based titanium implant coating: development and analytical characterization.

Microbial colonization and biofilm formation on implanted devices represent an important complication in orthopaedic and dental surgery and may result in implant failure. Controlled release of antibacterial agents directly at the implant site may represent an effective approach to treat these chronic complications. Resistance to conventional antibiotics by pathogenic bacteria has emerged in recent years as a major problem of public health. In order to overcome this problem, non-conventional antimicrobial agents have been under investigation. In this study, polyacrylate-based hydrogel thin coatings have been electrosynthesised on titanium substrates starting from poly(ethylene glycol diacrylate)-co-acrylic acid. Silver nanoparticles (AgNPs) with a narrow size distribution have been synthesized using a "green" procedure and immobilized on Ti implant surfaces exploiting hydrogel coatings' swelling capabilities. The coatings have been characterized by XPS and SEM/EDX, while their silver release performances have been monitored by ICP-MS. The antibacterial activity of these AgNP-modified hydrogel coatings was tested evaluating in vitro inhibition growth of Staphylococcus aureus, Pseudomonas aeruginosa and Escherichia coli, among the most common pathogens in orthopaedic infections. Moreover, a preliminary investigation of the biocompatibility of silver-loaded coatings versus MG63 human osteoblast-like cells has been performed. An important point of strength of this paper, in fact, is the concern about the effect of silver species on the surrounding cell system in implanted medical devices. Silver ion release has been properly tuned in order to assure antibacterial activity while preserving osteoblasts' response at the implant interface.

Antibiotic-modified hydrogel coatings on titanium dental implants.

Implant-associated infections represent an occasional but serious problem in dental and/or orthopaedic surgery. A possible solution to prevent the initial bacterial adhesion may be the coating of the implant surface with a thin layer of antibiotic-loaded biocompatible polymer. Hydrogels are one of the promising and versatile materials as antibiotic controlled release systems. In this work, antibiotic-modified poly(ethylene-glycol diacrylate) hydrogel coatings on titanium substrates were prepared by electrochemical polymerization and tested against methicillin resistant Staphylococcus aureus (ATCC 33591). Two different methods to load vancomycin and ceftriaxone were used. We show that the proposed titanium coatings displayed an interesting antibacterial activity, however, further studies on their effective cytotoxicity will furnish evidence of their real clinical efficacy.

Whole-body MR-DWIBS vs. [18F]-FDG-PET/CT in the study of malignant tumors: a retrospective study.

PURPOSE: Our aim was to assess the overall diagnostic accuracy of magnetic resonance diffusion-weighted whole-body imaging with background signal suppression (MR-DWIBS) compared with ([(18)F]-fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT), considered the reference standard of whole-body tumour imaging modalities, in a series of consecutive patients with malignant tumour. MATERIALS AND METHODS: Thirty-eight patients diagnosed with a malignant tumour over a 4-month period were enrolled in this retrospective, observational study. PET/CT and MR-DWIBS images were reviewed in double-blind manner by a nuclear medicine physician and radiologists with 4 years experience. Lesion size, standard uptake value (SUV) and apparent diffusion coefficient (ADC) were measured and calculated for each lesion. RESULTS: The qualitative analysis of MR-DWIBS and [(18)F]-FDG-PET/CT showed that two patients were negative at both techniques. MR-DWIBS was positive in 36 patients, 34 of whom were positive and two negative at [(18)F]-FDG-PET/CT, respectively. Two hundred and fifty-five lesions were identified by MR-DWIBS and 184 by [(18)F]-FDG-PET/CT, which was a significative discordance. Correlation between SUV and ADC of lesions positive at both techniques was not statistically significant. The mean difference between lesion size in [(18)F]-FDG-PET/CT and MR-DWIBS was not statistically significant. No correlation was found between glucose metabolism and water motion. CONCLUSIONS: MR-DWIBS may be used to evaluate localisation of parenchymal neoplasms but is less efficacious in characterising lymph-node and skeletal lesions. [(18)F]-FDG-PET/CT remains the best whole-body technique to identify lymph-node and skeletal lesions, but its limitation is identifying tumours with low glucose metabolism as in mucinous neoplasms. MR-DWIBS evaluation must be integrated with morphological images to increase MR diagnostic accuracy.

Ciprofloxacin-modified electrosynthesized hydrogel coatings to prevent titanium-implant-associated infections.

New promising and versatile materials for the development of in situ sustained release systems consisting of thin films of either poly(2-hydroxyethyl methacrylate) or a copolymer based on poly(ethylene-glycol diacrylate) and acrylic acid were investigated. These polymers were electrosynthesized directly on titanium substrates and loaded with ciprofloxacin (CIP) either during or after the synthesis step. X-ray photoelectron spectroscopy was used to check the CIP entrapment efficiency as well as its surface availability in the hydrogel films, while high-performance liquid chromatography was employed to assess the release property of the films and to quantify the amount of CIP released by the coatings. These systems were then tested to evaluate the in vitro inhibition of methicillin-resistant Staphylococcus aureus (MRSA) growth. Moreover, a model equation is proposed which can easily correlate the diameter of the inhibition haloes with the amount of antibiotic released. Finally, MG63 human osteoblast-like cells were employed to assess the biocompatibility of CIP-modified hydrogel coatings.

[Computerized digital thermometry in Raynaud's disease. Personal experience]. / La termometria digitale computerizzata nel morbo di Raynaud. Esperienze personali.

BACKGROUND: Computerized digital thermometry has been used for instrumental diagnosis of Raynaud's disease, that is characterized by diminution of the cutaneous temperature of the fingers and the late delayed recovery. Thermometry permits to measure basal temperature of the ten fingers, during cooling to 10 degrees C ("cold test") and the response, measuring temperature minute by minute up to 25 degrees. METHODS: In order to assess vasospastic ischemic disease a total of 66 subjects have been examined: 19 were asymptomatic for acrolocalised pathologies (control subjects) and 47 were symptomatic. RESULTS: No close correlation was observed between clinic and instrumental data. In fact 31.5% of the asymptomatic subjects had a "non-normal" reaction to the test; on the other hand, in the group of female over-50-years-old with symptoms suggesting Raynaud's disease, 38.5% of cases revealed "normal" instrumental patterns. Therefore no discriminating parameters were identified which might have allowed the instrumental identification of subjects suffering from Raynaud's disease compared to healthy individuals. CONCLUSIONS: In conclusion, computerised digital thermometry is a technique with a good level of sensitivity, while the specificity is scarce.

[Vascular manifestations in systemic sclerosis (scleroderma)]. / Le manifestazioni vascolari nella sclerosi sistemica (sclerodermia).

Progressive systemic sclerosis (PSS), a disease still of unknown origin, is a generalized autoimmune disorder characterized by immunological abnormalities, microvascular dysfunction, and tissue fibrosis. The mechanism leading to selective microvascular injury in PSS is not completely known, however it is now clear that neuropeptides, vascular endothelium, and disturbances in the regulation of fibroblast function are the three major contributors to the increased fibrosis of skin and internal organs. Thus, endothelial cell and fibroblast dysfunction may be linked through the paracrine activity of soluble endothelial cell products: the cytokine cascade (IL-1, TGF-beta-1, PDGF, TNF, etc.). In systemic sclerosis, the exaggerated generalized vasospastic tendency is clinically represented by Raynaud's phenomenon as shown by an early digital arterial closure after cold stimulation, and by an inadequate vasodilatory response to heat. In this review we summarize recently established data that center around the role of adhesion molecules, immune reactions, and aberrant fibroblast biology and metabolism in effecting vascular and connective tissue alterations in this disease. Only a better knowledge of the pathophysiological process involved in scleroderma might lead to the development of new therapeutic approaches.

[Cardiovascular disease and omega-3 fatty acids]. / Patologia cardiovascolare ed acidi grassi omega-3.

Fish oil is rich in the long chain omega-3 (omega-3) polyinsaturated fatty acids (PUFA), Pioneering studies of Dyerberg and Bang primarily originate interests in this way. The low incidence of acute myocardial infarction they verified within the Greenland Eskimos suggested that a high dietary omega-3 PUFA intake due to marine food might protect against coronary heart disease. They showed that the Eskimos had a beneficial lipid pattern and that their balance between pro-aggregatory thromboxanes and anti-aggregatory prostacyclins was shifted towards an anti-thrombotic state. The two major omega-3 fatty acids are decosapentaenoic acid (EPA C 20:5, omega 3), with five double bonds, and docosahexaenoic acid (DHA C 22:6, omega 3), with six double bonds. These fatty acids' significant effects include reduction of plasma triglycerides and lipoprotein levels as well as of platelets thrombogenicity in the microcirculation, which is due to effects on the mediators production derived from arachidonic acid (prostaglandins and leucotrienes), meddling in inflammatory and immune cell function, retarded atherosclerosis development. Experimental studies of atherogenesis and arterial thrombogenesis support the hypothesis that dietary omega-3 PUFA intake may play a leading role in primary or secondary prevention of coronary heart disease.

[Horton's giant cell arteritis]. / L'arterite gigantocellulare di Horton.

Giant cell arteritis (GCA) is a spontaneous vasculitic syndrome specifically involving the walls of medium and large arteries. While involvement of other arterial beds is occasionally identified, this syndrome is most frequently recognized when symptomatic involvement of the temporal arteries occurs. Vascular lesions are characterized by patchy granulomatous infiltrates composed of T cells, macrophages, histiocytes, and giant cells. A better prognosis depends on early recognition of the clinical symptoms and prompt treatment. Diagnosis was based on the 5 clinical criteria previously used by the American College of Rheumatology (1990): 1) age 50 years or older; 2) new localized headache; 3) temporal artery tenderness or decrease in temporal artery pulse; 4) erythrocyte sedimentation over 50 mm/ hour; 5) abnormal result on artery biopsy. Giant cell arteritis was considered a rare disease under age 50; however, it is now known to be an important and significant cause of morbidity and mortality in elderly people. Therefore early recognition and treatment with corticosteroid are very important. There is no general agreement concerning the initial dosage, 40-65 mg/day are commonly recommended. After a few months the majority of patients can be treated with a low maintenance dosage of prednisolone (5 to 7.5 mg/day). The mean duration of treatment is about 5 years. The literature is reviewed and the clinical implications of this disease are discussed.

[Vascular "remodeling"]. / Il "remodeling" vascolare.

Vascular remodeling means a specific organization of the vascular wall around a diminished lumen as to the before existing conditions, with consequent vascular geometry modification. This organization comes from the response of all vascular components (endothelium, muscular cells, connective component, etc.) to physical and chemical stimuli. Particular behaviour of the vascular wall has lately been pointed out, both in long known pathologies (arteriosclerosis, arterial hypertension, diabetes mellitus, arteriosclerotic aneurysms) and in situations involving both physiopathology (ischaemia-reperfusion, angiogenesis) as therapy (angioplasty).

[The concept of quality of life in cardiac failure]. / Il concetto della qualità della vita in corso di scompenso cardiaco.

Chronic congestive heart failure is a common yet devastating syndrome and is a leading cause of morbidity and mortality in the industrialised countries. The incidence and prevalence of chronic congestive heart failure is increasing, placing a growing burden on the health care system. Despite many advances in treatment for heart disease, chronic heart failure is a terminal condition with a death rate as high as that for many malignant tumours. Patients suffering from chronic congestive heart failure report a poor quality of life because of physical symptoms, functional disability, emotional and economic burdens, frequent hospitalisations, and poor prognosis. In the context of heart failure, mortality risk (prognosis quoad vitam) can be measured using a variety of physiological variables; left ventricular (LV) dysfunction plays a primary role in the pathogenesis of congestive heart failure and correlates with prognosis, but a strong quantitative relation between exercise performance and indexes of LV function has not been demonstrated. This finding underscores the importance of psychosocial interventions in improving the quality of life and care outcomes for patients with heart failure. For this reason, questionnaires of quality of life, assessed by direct patient self-reports, have recently been imposed in cardiology, they have been used specially for evaluating most treatment of cardiac failure. The refinement of a definition of quality of life improved methods to study quality of life will contribute to a better understanding of this complex concept in heart failure patients.

[Hyperhomocysteinemia: a new independent vascular risk factor?]. / Iperomocisteinemia: un nuovo fattore indipendente di rischio vascolare?

The positive correlation existing between hyperhomocysteinemia and atherosclerosis has firmly been established through data derived from numerous epidemiologic and experimental observations as well as from intervention trials. Although most of the clinical data have been obtained in relation to coronary heart disease, hyperhomocysteinemia is also observed in patients with cerebral and peripheral arterial occlusive disease or peripheral venous thrombosis. The prevalence of the heterozygous state is today estimated about 1 to 2 percent of the population. Mild and moderate hyperhomocysteinemia have recently been proposed as an additional and independent risk factor for vascular disease. In this review we therefore describe recent findings about the pathogenesis of hyperhomocysteinemia and their implications for optimal drug therapy.

[Morphological and functional aspects of the cardiovascular system related to aging: does "aging heart" exist?]. / Aspetti morfologici e funzionali dell'apparato cardiovascolare nell'età avanzata: esiste il "cuore senile?"

Elderly people are the most rapid growing segment of society, and heart disease is the most common cause of death in this population. The aging process is associated with anatomic and physiologic alterations in the cardiovascular system; consequently, the manifestations of disease in the geriatric population differ from those involving younger patients. To formulate diagnosis of "aging heart" in older patient may be difficult, because of atypical symptoms or of the acceptance of symptoms as manifestations of old age. Aging is, moreover, often associated with a decline in physical activity, which may result in cardiovascular "deconditioning". The treatment strategy is the same as in younger patients, but the higher incidence of adverse effects and complications demands special awareness. In this article we discuss about age-related structural and functional changes that occur in the cardiovascular system, including changes in the heart muscle, valves, conduction system and major arteries.

[Pulmonary embolism of paraneoplastic origin]. / L'embolia polmonare da causa paraneoplastica.

Thromboembolic disease (TE) is an important cause of in-hospital morbidity and mortality. The relationship between cancer and abnormalities of blood coagulation has been recognized for well over a century. Deep venous thrombosis (DVT) of the lower extremities is the most common cause of thromboembolic disease, but pulmonary embolism, upper extremity vein thrombosis, disseminated intravascular coagulation, and other, more unusual, clinical events, may occur. Unexplained TE may serve as a marker for the presence of a hidden tumor. The frequency of pulmonary embolism (PE) among patients with a malignant neoplasm at necropsy is highly increased in the elderly patients. Among subjects with a malignant neoplasm, patients with pancreatic and gastric cancer (mucin-secreting adenocarcinomas), cancer of the large bowel and women with ovarian cancer had the highest frequency of PE. Old age, female sex, gastrointestinal and ovarian cancers must be considered as a significant risk factor for PE. The potentially responsible mechanisms for the thrombotic events, clinical manifestations, diagnostic implications and aspects of treatment of TE in malignant disease are discussed.

[Circadian patterns of ischemic events]. / Il comportamento circadiano degli eventi ischemici.

These is evidence of circadian variations in the occurrence of ischemic events such as: silent myocardial ischemia, stable angina, instable angina, acute myocardial infarction, sustained ventricular tachycardia, cerebral infarction, transient ischemic attack (TIA) and sudden cardiac death. In the general population many cardiovascular disorders occur with the greatest frequency between 6 and 12 a.m. (i.e. after awakening). Blood pressure, too, follows a distinct circadian pattern. Factors affecting circadian variations in cardiovascular disorders include physiological determinants, such as heart rate, catecholamine release, and platelet aggregation-which themselves cyclically vary-, and exogenous factors such as mental stress, anxiety, and physical activity. In chronotherapy, circadian variations in disease states and in the pharmacodynamic properties of drugs are exploited to improve prevention and treatment. Characterization of diseases states with this approach allows more accurate determination of the times when patients are at highest risk and therefore in greatest need of preventive measures; it also provides a mechanism for designing optimal drug regimens. In this review we therefore describe recent findings about the effects of biorhythms on cardiovascular disorders and their implications for optimal drug therapy.

[Liver cirrhosis and cardiovascular system]. / Cirrosi epatica ed apparato cardiovascolare.

The patient with hepatocellular disease shows marked vasodilatation, accompanied by hyperdynamic circulation and opening of arteriovenous shunts. The effect of these circulatory changes and especially the profound vasodilation has only recently been investigated in detail. In patients with hepatocellular failure the extremities are flushed, the pulses bounding, the cardiac output increased and the blood pressure low. The circulation resembles what found with systemic arteriovenous fistulae. The peripheral vasodilatation and splanchnic venous pooling reduce the effective blood volume so activating baroreceptors. The secondary events which follow the vasodilation include stimulation of the sympathetic nervous system. This serves to counteract the tendency to arterial hypotension and probably contributes to renal hypoperfusion and to the hepatorenal syndrome development. The nature of the concerned vasodilators remains speculative, but is likely to be multiple. Whatever its nature, the substance might be formed by the sick hepatocyte, fail to be inactivated by it or bypass it through intra- or extra-hepatic portal systemic shunts. In cirrhosis the cardiac index and reduced systemic vascular resistance correlate with the Child's grade of liver failure. This article provides an overview of the general vasodilatory state and its effects on various organs. The mechanisms and the different vasoactive substances that might be responsible are also discussed.

[Non-vascular claudication or "painful leg syndrome"]. / Le claudicatio non vascolari ovvero la "sindrome delle gambe dolenti".

All angiologists commonly find that a considerable proportion of the persons referred to an angiology clinic are in fact suffering from other pathologies. Many of these patients often complain of polyhedric, vague symptoms, sometimes pyrotic and sometimes disguised as cramps, frequently accompanied by paresthesia or hypasthenia of the lower limbs which is generally justified, above all in elderly patients, as being caused by "circulation disorders". The authors felt the need to perform this study with the aim of both evaluating the prevalence of so-called non-vascular claudication or pseudo-claudication, defined here as "painful leg syndrome", and to identify simple and low-cost clinical and instrumental parameters, which may be useful not only to the general practitioner but also to the angiologist. A large number of patients with "false claudication" (43%) was diagnosed in this series and the most frequent cause was neurological pathology (68%). Anamnesis and an objective examination should, if correctly performed, be sufficient for a rapid diagnosis of non-vascular pathology and should therefore be useful in limiting the number of requests for Doppler tests, thus reducing waiting times and management costs.

[Neurocardiogenic (or vasovagal) syncope]. / La sincope neurocardiogena (o vasovagale).

Syncope is a common clinical problem in a general population that is responsible for a significant number of emergency department visits (3%) and hospitalizations (1%) each year. The clinical spectrum of etiologies of syncope includes disorders classified as cardiovascular, noncardiovascular and unexplained. A majority of syncopal events are believed to be caused by vasovagally mediated episodes by hypotension and bradycardia. Although vasovagal syncope is essentially equivalent to simple fainting, the physiologic events that lends to this phenomena are complex. Although not completely understood, the most commonly held theory explaining vasovagal syncope involves a series of reflexive interactions between cardiac mechanoreceptors and the autonomic nervous system. Until the advent of head upright tilt table testing, diagnosis of vasovagal syncope has been an assumption, made when all other causes have been eliminated. Frequently an accurate history, a physical examination and a standard ECG are enough to formulate a correct diagnosis. Head-up tilt test must be considered in patients with an unknown diagnosis, before starting invasive investigation. Tilt table testing, either alone or with a graded-dose infusion of isoproterenol, allows reproduction of the syncopal event in susceptible individuals and monitoring of the patients physiologic responses during the episode. Direct observation and documentation of symptoms permit accurate diagnosis and yield information vital to treatment and symptom control. This article reviews our current understanding of the mechanisms involved in the development of neurally mediated syncope.

[The medical angiology outpatient clinic today. The authors' personal experience and operational proposals]. / L'ambulatorio di angiologia medica oggi. Esperienza personale e proposte operative.

Over the past two decades the demographic characteristics of our population have changed resulting in a major increase in older age groups and a consequent real increase in the prevalence of vascular diseases' of an atherosclerotic type. This had led to an almost exponential increase in the number of requests for instrumental tests, such as Doppler. The aim of this study, the outcome of a review of the patients attending our outpatient clinic over the past twelve months, was to evaluate the current role of a clinic specialising in medical angiology compared to the changing requests for assistance and to elaborate operating proposals for clinics at various levels, aiming to attain the efficacy and efficiency of outpatient activity in accordance with the objective limitations of health spending and current legislation.

[The vascular changes in arterial hypertension]. / Le modificazioni vascolari nell'ipertensione arteriosa.

Although the causes of high blood pressure vary, it is becoming clear that sustained hypertension is associated with changes in cardiovascular structure: left ventricular hypertrophy, decrease in big-medium arteries compliance and increased wall thickness of small arteries. To some extent, these alterations are natural physiological responses and are protective. However, the risk of circulatory death is closely related to left ventricular hypertrophy, and therefore, it is suggested increasingly that effective antihypertensive treatment requires normalization not only of blood pressure but also of vascular structure. The purpose of this brief review is to identify the type of functional and structural changes that are found in arteries of hypertensive individuals.

[Severe pulmonary arterial hypertension and primary antiphospholipid antibodies syndrome]. / Ipertensione arteriosa polmonare severa e sindrome da anticorpi antifosfolipidi primaria.

A young patient with severe pulmonary hypertension of thromboembolic origin due to recurrent deep vein thrombosis is described. Although he presented no signs of systemic lupus erythematous, a high quantity of cardiolipin antibodies was found in his serum. Therefore, we discuss a possible association between the primary antiphospholipid antibodies syndrome and pulmonary embolic events.