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Biomedical subjects

M Ferrari

Publications and source records attributed to M Ferrari.

At least 19 recordsLinked to original sources

Changes in autonomic modulation to the heart and intracellular catecholamines. A longitudinal study in differentiated thyroid carcinoma during short-term hypothyroidism and thyroid hormone replacement.

BACKGROUND: The effects of thyroid deprivation on the autonomic modulation to the heart remain controversial. METHODS: In this study in patients followed for thyroid carcinoma, we investigated (1) heart rate variability parameters and the baroreflex gain and (2) intracellular catecholamine levels in circulating lymphocytes during short-term hypothyroidism (phase 1) and after reinstitution of TSH-suppressive thyroid hormone replacement (phase 2). RESULTS: The RR interval value (p < 0.01) and systolic blood pressure (p < 0.05) were higher in phase 1 than in phase 2. The low-frequency/high-frequency (LF/HF) ratio was significantly lower in the hypothyroid state (p < 0.05), with a higher HF component (p < 0.05). After adjusting for mean RR interval in the regression model, the difference between the power of RR interval oscillations calculated in the two states was greater for the LF band (p = 0.005) and it was borderline significant for the HF band (p = 0.052). The baroreflex gain alpha(LF) index was similar in the two phases. The stimulus-induced cellular production of norepinephrine and epinephrine in peripheral blood mononuclear cells was significantly higher in phase 2. CONCLUSION: The neurally-mediated influences on the sinus node and the study of intracellular catecholamine production suggest a reduced sympathoexcitation in hypothyroidism compared with the treatment phase. The early increase in blood pressure observed after thyroid hormone withdrawal is not due to impaired sensitivity of the baroreflex arc.

Autonomic Nervous System↗

Pharmacokinetic and demographic markers of 5-fluorouracil toxicity in 181 patients on adjuvant therapy for colorectal cancer.

BACKGROUND: The relationship between 5-fluorouracil (5-FU) pharmacokinetics and toxicity following i.v. bolus administration has not been extensively studied. PATIENTS AND METHODS: One hundred and eighty-one patients on adjuvant therapy with 5-FU plus leucovorin for colorectal cancer were the study population. 5-FU pharmacokinetics was determined on day 2 of the first, third, and fifth cycles; type and the grade of adverse reactions were recorded on the next cycle. RESULTS: The 5-FU area under the curve (AUC) measured at the first cycle ranged between 146 and 1236 mg x min/l and was significantly correlated with drug dose, patients' body weight (BW) and gender, females having higher AUCs. These covariates explained only 23% of AUC variability. AUC and age were the only covariates which discriminated between toxic (grade > or =2) and nontoxic cycles (grade <2), with an optimal AUC cut-off value of 596 mg x min/l. Such a correlation was lost during the next cycles following dose reduction because of toxicity in 80 patients. CONCLUSIONS: A method for calculating the initial 5-FU dose is proposed which takes into account patient BW, gender and a target AUC of 596 mg x min/l. Nevertheless, it appears that a substantial part of 5-FU toxicity is not linked to pharmacokinetic factors and dose adjustments must still be on the basis of careful clinical surveillance.

Adult↗

The adhesive strength of non-spherical particles mediated by specific interactions.

The specific adhesive interaction between a non-spherical particle and a cell layer under a linear shear flow is analyzed. The effect of the characteristic particle size, expressed in terms of the volume V, and shape, expressed in terms of the aspect ratio gamma, on the adhesive strength is investigated. It is shown that for a fixed shape, there exists an optimal volume V(opt) for which the adhesive strength has a maximum. A surprisingly accurate relationship has been derived between the optimal volume V(opt) and the ratio microS/m(r) (wall shear stress to the receptors surface density) having the form V(opt)=alpha(m(r)/microS)(beta). Also, oblate particles have been shown to adhere more effectively to the biological substrate than classical spherical particles for the same volume V. As a consequence, non-spherical particles can carry a larger amount of drugs and contrast agents than classical spherical particles with the same adhesive strength, improving the therapeutic and imaging efficacy. The formulae and the procedures described in the present work can guide the optimal design of intravascularly injectable micro/nano carriers.

Adhesives↗

Technique sensitivity associated with air-drying of HEMA-free, single-bottle, one-step self-etch adhesives.

OBJECTIVES: This study examined the effect of air-drying on bond strength to dentin and nanoleakage in resin-dentin interfaces using HEMA-free one-step self-etch adhesives. METHODS: Twelve teeth had their occlusal dentin exposed and split in half. In the group of G-BOND (GB), the adhesive was dried gently or vigorously on each slit half tooth, and then light-cured. In the group of the experimental adhesive (EX), three coats of adhesive were dried using a single air-drying process prior to light-curing or dried after each of three coats of adhesive before light-curing. The split specimens were built-up with resin composite and then subjected to microtensile bond strength testing and TEM examination. RESULTS: GB showed significantly higher bond strength after vigorous drying than after gentle drying. Three teeth of from EX group showed higher bond strength after triple drying than after single drying, while two teeth showed no significant difference. Droplets were revealed in the adhesive layer after gentle drying with GB, and silver deposits existed along the interfaces in all groups. SIGNIFICANCE: The bonding quality to dentin may be improved by using an accelerated air-drying technique; although it is impossible to remove intrinsic dentin moisture that is drawn upwards from dentin tubules.

Acid Etching, Dental↗

The effective dispersion of nanovectors within the tumor microvasculature.

The effective longitudinal diffusion of nanovectors along non-permeable and permeable capillaries has been studied considering the contribution of molecular and convective diffusion based on the Taylor's theory of shear dispersion. The problem is of importance in the transport of nanovectors used for the intravascular delivery of drugs and contrast agents. It has been shown that for a given capillary size and hemodynamic conditions a critical radius acr exists for which the effective longitudinal diffusion along the capillary has a minimum: Nanovectors with a < acr diffuse mainly by Brownian diffusion whereas nanovectors with a < acr diffuse mainly by convection and the effective diffusion coefficient grows with a. In permeable conduits, the effective diffusion reduces significantly compared to normal non-leaky vessels and it has been derived that acr grows almost linearly with the hydraulic permeability Lp of blood vessels. It has been shown that the blood conduits with the largest effective longitudinal diffusivity could be preferentially targeted by the circulating vectors. Based on these findings, the following strategies are proposed to increase the number of nanovectors targeting the tumor vessels: (i) The use of nanovectors with a critical radius for normal vessels, (ii) the injecting of bolus of nanovectors with different radii, and (iii) the normalization of the tumor vasculature. Finally, it has been emphasized that the size of the vector should be selected depending on the body district where the tumoral mass is developing and on the type, malignancy, and state of the tumor.

Animals↗

Patients with Cushing's syndrome have increased intimal media thickness at different vascular levels: comparison with a population matched for similar cardiovascular risk factors.

Cushing's syndrome (CS) is associated with high cardiovascular risk. The aim of this study was to analyze intimal media thickness (IMT) in patients with CS and compare them with subjects matched for similar conventional and independent cardiovascular risk factors. Twenty eight patients with CS (mean age: 40.7 +/- 2.5 y) and 28 subjects (mean age: 41.1 +/- 14 y) matched for sex, age, smoking habit, body mass index, blood pressure levels, glucose and lipid metabolism were evaluated. IMT was measured at right and left common carotid (CC), carotid bulb (BC), aorta (Ao) and femoral (F) levels by B-echo-Doppler ultrasonography. Although parameters of cardiovascular risk factors did not differ statistically between patients and controls, IMT was significantly increased (right and left CC-IMT, p < 0.05; right and left BC-IMT, p < 0.01, Ao-IMT p < 0.05) and wall plaques were more common (14.2 % VS. 7.1 %) in patients. In CS patients, CC-IMT and F-IMT correlated positively and significantly with fasting glucose (right CC-IMT: r (2) = 0.37, p = 0.05; left CC-IMT: r (2) = 0.43, p = 0.02; right F-IMT: r (2) = 0.57; p < 0.01; left F-IMT: r (2) = 0.47, p = 0.01) and HOMA index (left CC-IMT: r (2) = 0.64, p < 0.01 and left F-IMT: r (2) = 0.48, p < 0.05). The CS patients' waist-to-hip ratio (WHR) was evaluated and correlated positively and significantly with CC-IMT (right: r (2) = 0.53, p = 0.01 and left: r (2) = 0.44, p = 0.05). No correlation was found between IMT and cortisol levels, however. In conclusion, patients with CS have more severe atherosclerotic damage than a population matched for similar cardiovascular risk factors. Multiple events related to long-term cortisol effects on metabolism and at vascular and endothelial sites may increase the risk of cardiovascular damage in patients with CS.

Adolescent↗

Soya isoflavone-enriched cereal bars affect markers of endothelial function in postmenopausal women.

Soya isoflavones are thought to be cardioprotective due to their structural similarity to oestrogen. In order to investigate the effect of soya isoflavones on markers of endothelial function we conducted a randomised, double-blind, placebo-controlled, cross-over study with thirty healthy postmenopausal women. The women consumed cereal bars, with or without soya isoflavones (50 mg/d), for 8 weeks, separated by an 8-week washout period. Systemic arterial compliance (SAC), isobaric arterial compliance (IAC), flow-mediated endothelium-dependent vasodilation (FMD) and nitroglycerine-mediated endothelium-independent vasodilation (NMD) were measured at the beginning of the study and after each intervention period. Blood pressure (BP) and plasma concentrations of nitrite and nitrate (NOx) and endothelin-1 (ET-1) were measured at the beginning and end of each intervention period. NMD was 13.4 (SEM 2.0)% at baseline and 15.5 (SEM 1.1) % after isoflavone treatment compared with 12.4 (SEM 1.0)% after placebo treatment (P=0.03). NOx increased from 27.7 (SEM 2.7) to 31.1 (SEM 3.2) microM after isoflavones treatment compared with 25.4 (SEM 1.5) to 20.4 (SEM 1.1) microM after placebo treatment (P=0.003) and a significant increase in the NOx:ET-1 ratio (P=0.005) was observed after the isoflavone treatment compared with placebo. A significant difference in SAC after the isoflavone and placebo treatment was observed (P=0.04). No significant difference was found in FMD, IAC, BP and ET-1. In conclusion, 8 weeks' consumption of cereals bars enriched with 50 mg soya isoflavones/d increased plasma NOx concentrations and improved endothelium-independent vasodilation in healthy postmenopausal women.

Biomarkers↗

Evidence for associations between common polymorphisms of estrogen receptor beta gene with homocysteine and nitric oxide.

BACKGROUND: Homocysteine and asymmetric dimethylarginine (ADMA) affect nitric oxide (NO) concentration, thereby contributing to cardiovascular disease (CVD). Both amino acids can be reduced in vivo by estrogen. Variation in the estrogen receptor (ER) may influence homocysteine and ADMA, yet no information is available on associations with single nucleotide polymorphisms in the estrogen receptor genes ERalpha (PvuII and XbaI) and ERbeta (1730G-->A and cx + 56 G-->A). OBJECTIVE: To find relationships between common polymorphisms associated with cardiovascular disease and cardiovascular risk factors homocysteine and ADMA. METHODS: In a cross-sectional study with healthy postmenopausal women (n = 89), homocysteine, ADMA, nitric oxide metabolites (NOx), plasma folate and ERalpha and beta polymorphisms ERalpha PvuII, ERalpha XbaI; ERbeta 1730G-->A (AluI), ERbeta cx + 56 G-->A (Tsp509I) were analyzed. RESULTS: Women who are homozygotic for ERbetacx + 56 G-->A A/A exhibited higher homocysteine (p = 0.012) and NOx (p = 0.056) levels than wildtype or heterozygotes. NOx concentration was also significantly affected by ERbeta 1730 G -->A polymorphism (p = 0.025). The ERbeta (p < 0.001) and ERalpha (p < 0.001) polymorphisms were in linkage disequilibrium. CONCLUSIONS: Women who are homozygotic for ERbetacx + 56 G-->A A/A may be at increased risk for cardiovascular disease due to higher homocysteine levels.

Aged↗

The adhesion between fibre posts and composite resin cores: the evaluation of microtensile bond strength following various surface chemical treatments to posts.

AIM: To evaluate the influence of various surface treatments to fibre posts on the microtensile bond strength with different composite resins. METHODOLOGY: A total of 110 fibre posts were randomly divided into five groups, according to the surface pre-treatment performed. Group 1: immersion in 24% H(2)O(2) for 10 min and silanization for 60 s; group 2: immersion in 10% H(2)O(2) for 20 min and silanization for 60 s; group 3: immersion in 4% hydrofluoric acid gel for 60 s and silanization for 60 s; group 4: silanization of the post surface for 60 s and application of the bonding agent G-Bond; group 5: silanization of the post surface for 60 s (control group). After treatment, two posts were randomly selected from each group to evaluate the morphological aspect of the post surface with scanning electron microscopy. The remaining posts in each group were divided into five subgroups of five posts each, which differed in the type of composite resin used for the core build-up. Post-core strength were calculated and the differences among experimental groups were analysed with two-way anova and the Tukey test (alpha = 0.05). RESULTS: The post-core strengths achieved in groups 1 and 2 were significantly higher (P < 0.05), than those of groups 3, 4 and 5. The post-core strength in the control group was significantly lower (P < 0.05) than all other groups. CONCLUSIONS: Hydrogen peroxide and hydrofluoric acid both modified the surface morphology of fibre posts and with silane, significantly enhanced the interfacial strength between them and core materials.

Acrylic Resins↗

A case series of young stroke in Rome.

In this hospital case series study we enrolled 394 consecutive ischemic stroke patients aged 14-47 years, all of whom were submitted to a diagnostic protocol. We evaluated the incidence of cerebral ischemia in young adults, as well as the risk factors and the etiopathogenesis of this pathology. Modified diagnostic criteria adopted from the TOAST and Baltimore-Washington Cooperative Young Stroke Study were used for the etiologic classification. The crude annual incidence rate was 8.8/100,000 (95% CI 7.7-9.9), which is in keeping with the rates reported in comparable registries. Risk factors were distributed as follows: smoking in 56% of patients, hypertension in 23%, dyslipidemia in 15%, migraine in 26%, and diabetes mellitus in 2%. Oral contraceptives were being taken by 38% of the women enrolled. The etiology of stroke in the patients was as follows: cardioembolism in 34%, atherothrombosis in 12%, non-atherosclerotic vasculopathies in 14% (including arterial dissection in 12%), other determined causes in 13%, lacunar stroke in 2.5%, migraine in 1%, and undetermined causes in 24%. Despite its biased sampling frame, this large hospital case series, in which risk factor distribution and etiopathogenesis were investigated, stresses the need for an adequate diagnostic approach in young ischemic patients.

Adolescent↗

Metabolic and hemodynamic features of elderly patients undergoing beating heart coronary artery bypass graft surgery.

AIM: Coronary artery bypass graft (CABG) surgery, nowadays, is increasingly performed in patients who are older and have more comorbidities than subjects operated on a decade ago. In this study, we investigated metabolic and hemodynamic features of elderly patients with single vessel coronary artery disease (CAD), undergoing beating heart coronary artery bypass graft (BHCABG) surgery. METHODS: Twenty-five elderly patients, ages 73-78 years, with isolated left anterior descending artery (LAD) disease, were enrolled and compared to a younger similar group of 25 patients, mean age 48+/-1.2 years. A single vessel left internal mammary artery (LIMA) to LAD BHCABG was performed in all patients. Duration of temporary LAD occlusion was 9.8+/-0.5 min in the elderly group, and 10+/-0.4 min in the younger group. Myocardial arterial-venous differences in glucose, lactate, and creatine phosphokinase (CPK) were performed at different time points: preoperatively in the operating room (T0); at the end of the grafting procedure (T1); and before closing the chest (T2). Left ventricular stroke work index (LVSWI), as an indicator of global function of left ventricle, were recorded at T0, T1, T2, 6 (T3) and 48 (T4) hours postoperatively. RESULTS: Preoperative glucose extraction, observed in both groups, did not augment during and after surgery. In addition, neither lactate nor CPK were released in the coronary sinus during temporary LAD occlusion and following reperfusion in either group. Similarly, no significant changes in LVSWI were observed intra- and perioperatively between the two groups. CONCLUSIONS: Cardiac metabolism, hemodynamic parameters and global left ventricular function were not affected in either group by brief LAD occlusion during BHCABG, suggesting that BHCABG is a well-tolerated surgical approach, which can be safely attempted in patients of any age.

Age Factors↗

Laparoscopic assisted aortic surgery. A review.

We give an overview of different laparoscopic assisted techniques to perform aortic surgery. In a meta-analysis the paper describes the combined experience of two vascular surgical centers who together have performed more than 524 laparoscopic assisted aortic procedures. Basically the following techniques can be used to perform a laparoscopic assisted procedure: 1) transperitoneal approach (the Alimi procedure); 2) hand assisted laparoscopy (the Ferrari technique); 3) left retrocolic laparoscopic assisted; 4) combining laparoscopic assisted and total laparoscopy techniques. In all cases a transperitoneal approach was chosen to dissect the aorta. This was either accomplished directly or using a left retrocolic access originally described by Dion as the apron technique. In some cases a hand assist device was used, which permits the surgeon to introduce the non dominant hand while maintaining the pneumoperitoneum. The mortality in abdominal aortic aneurysm (AAA) patients in either center did not exceed 1.8%. ICU stay, postoperative ileus and length of stay were significantly shorter compared to patients with a full length incision. The Pisa group showed that there is still a significant reduction of operating time as well as aortic cross clamping time beyond the learning curve of the first 30 patients. The analysis of the pooled data shows that even in AAA patients the laparoscopic assisted procedure can be performed with operating times of less than 3 h and hospital stays up to 4 days, which we only know from endovascular aneurysm exclusion. This is the first publication of hand assisted laparoscopic endoaneurysm repair involving a large number of patients. The operations can be performed with expediency and safety. We can use these laparoscopic procedures to perform even complex aortic operations including suprarenal aneurysms with revascularization of the renal and visceral arteries. An outlook of future developments including stapling technology is given.

Angiography↗

Two patients with COMT inhibitor-induced hepatic dysfunction and UGT1A9 genetic polymorphism.

The authors report two cases of catechol-O-methyltransferase (COMT) inhibitor-induced asymptomatic hepatic dysfunction in women with Parkinson disease. The patients were genotyped for the UDP-glucuronosyltransferase (UGT) 1A9 gene (which encodes the main COMT inhibitor-metabolizing enzyme), and found to carry mutations leading to defective glucuronidation activity. This suggests that UGT1A9 poor metabolizer genotype(s) may be a predisposing factor for COMT inhibitor-induced hepatotoxicity.

Adult↗

Major myofibrillar changes in early onset myopathy due to de novo heterozygous missense mutation in lamin A/C gene.

Mutations in the lamin A/C gene (LMNA) have been associated with neuromuscular diseases and more complex syndromes, involving bone and adipose tissue. We report on a case of early onset myopathy due to a heterozygous LMNA mutation in exon 9, characterized by the presence of a marked number of cytoplasmic bodies with extensive myofibrillar abnormalities and Z-disk disruption in skeletal muscle. This case suggests there is a need to increase the list of genes to be screened in patients with myofibrillar myopathy.

Child↗

Levels of F2-isoprostanes in systemic sclerosis: correlation with clinical features.

OBJECTIVE: Oxidative stress may be one of the important complex pathogenetic mechanisms that lead to damage in scleroderma; free radicals may provoke endothelial injury, fibroblast proliferation and fragmentation of autoantigens favouring induction of autoantibodies. The present study investigates the oxidant status in scleroderma patients by measuring the urinary concentration of 8-isoprostaglandin-F2alpha, an F2-isoprostane, and a product of free radical-mediated peroxidation of arachidonic acid. METHODS: Forty-three scleroderma patients (42 women and 1 man, mean age 54.1 yr, mean disease duration 9.0 yr) underwent clinical evaluation and instrumental investigations in order to assess skin, vascular, lung and heart involvement. Von Willebrand factor was evaluated as marker of vascular dysfunction in 36 out of the 43 cases. The urinary level of 8-isoprostaglandin-F2alpha was measured in all scleroderma patients and in the 43 age- and sex-matched healthy controls. RESULTS: Urinary levels of 8-isoprostaglandin-F2alpha were higher in scleroderma patients than in the healthy control group (341.7 vs 147.6 pg/mg creatinine; P < 0.001). Values of 8-isoprostaglandin-F2alpha were strongly correlated with the nailfold videocapillaroscopy pattern and lung involvement (P = 0.002 and 0.003, respectively), showing increasing levels with the progression of pulmonary severity. Correlation between 8-isoprostaglandin-F2alpha level and von Willebrand factor narrowly failed to reach statistical significance (P = 0.05). There was no correlation between 8-isoprostaglandin-F2alpha concentration and disease activity, vascular, skin and heart involvement, disease pattern or autoantibody profile. CONCLUSIONS: Our study further supports the role of oxidant stress in the pathogenesis of scleroderma, showing a strong correlation between a marker of free radical damage with both the severity of lung involvement and the videocapillaroscopic patterns.

Adult↗