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Biomedical subjects

R Fanelli

Publications and source records attributed to R Fanelli.

At least 19 recordsLinked to original sources

Organic tracers identification as a convenient strategy in industrial landfills monitoring.

Today, a significant environmental problem is due to the presence of industrial landfills, some of them old, which can release toxic compounds into the environment (Chemosphere 42 (2001) 415; Chemosphere 31 (1995) 3455). The identification of directly linked to the leachate tracers of contamination in the wells around the landfills, as early markers of a potential risk for the environment and/or man, is a good strategy for an early evaluation of contamination. Our protocol developed for wells water characterization is based on solid phase extraction combined with GC-MS and HPLC-MS/MS. In this way a list of organic contaminants of a specific industrial landfill is obtained, giving a solid basis also for the risk assessment. Here we present some specific examples and the use of these pollutants for environmental monitoring.

Environmental Monitoring↗

Persistent organic pollutants in food: public health implications.

Persistent organic pollutants are a heterogeneous group of chemicals sharing a number a common properties, including long term persistence and diffusion in the environment, and bioaccumulation through the food chain. Animal experiments and epidemiological studies suggest that the most sensitive adverse effects, such as disturbances on metabolism, development, and reproductive system, may occur in the range of current human exposure. Although the potential cancer risk of persistent organic pollutants remains undefined, the implementation of actions to reduce the exposure to these substances, which mainly occurs through the diet, is important.

Environmental Exposure↗

Screening for silent myocardial ischaemia in type 2 diabetic patients with additional atherogenic risk factors: applicability and accuracy of the exercise stress test.

OBJECTIVE: Coronary artery disease (CAD), a major cause of mortality in patients with type 2 diabetes (T2D), is often diagnosed late because of silent myocardial ischaemia (SMI). Exercise electrocardiogram testing (ECG) stress is the most utilized screening test for SMI. Its applicability and accuracy, which have never been reported in asymptomatic high-risk T2D patients, have been investigated in this study. DESIGN: A cross-sectional study with coronary angiography as the gold standard for detecting CAD was used. METHODS: Two hundred and six consecutive T2D patients, without symptoms and resting ECG signs of ischaemia but with peripheral vascular disease (PVD) and/or > or = two atherogenic factors, were studied. Ischaemia at ECG stress was indicated by horizontal or downsloping ST segment depression > or =1 mm at 0.08 s after the J point. CAD was defined by stenosis > or =70%. RESULTS: Only 141/206 (68%) patients had a diagnostic test: 27 (19%) tested positive and 114 (81%) tested negative. Coronary angiography in 71 patients (the 27 who tested positive and 44 randomly selected patients who tested negative) indicated a CAD prevalence of 29% and the ECG stress accuracy was 79%. 'False negative' patients (18%) had a higher prevalence (P<0.01) of long duration of diabetes and PVD. CONCLUSIONS: This is the first study which provides insights into the applicability and accuracy of ECG stress in screening SMI in high-risk patients with T2D. Due to the high prevalence of CAD, alternative screening tests in patients unable to perform the test and in those with a high chance of being 'false negative' should be looked for and validated.

Coronary Angiography↗

Purification of the aldehyde oxidase homolog 1 (AOH1) protein and cloning of the AOH1 and aldehyde oxidase homolog 2 (AOH2) genes. Identification of a novel molybdo-flavoprotein gene cluster on mouse chromosome 1.

We report the cloning of the AOH1 and AOH2 genes, which encode two novel mammalian molybdo-flavoproteins. We have purified the AOH1 protein to homogeneity in its catalytically active form from mouse liver. Twenty tryptic peptides, identified or directly sequenced by mass spectrometry, confirm the primary structure of the polypeptide deduced from the AOH1 gene. The enzyme contains one molecule of FAD, one atom of molybdenum, and four atoms of iron per subunit and shows spectroscopic features similar to those of the prototypic molybdo-flavoprotein xanthine oxidoreductase. The AOH1 and AOH2 genes are 98 and 60 kilobases long, respectively, and consist of 35 coding exons. The AOH1 gene has the potential to transcribe an extra leader non-coding exon, which is located downstream of exon 26, and is transcribed in the opposite orientation relative to all the other exons. AOH1 and AOH2 map to chromosome 1 in close proximity to each other and to the aldehyde oxidase gene, forming a molybdo-flavoenzyme gene cluster. Conservation in the position of exon/intron junctions among the mouse AOH1, AOH2, aldehyde oxidase, and xanthine oxidoreductase loci indicates that these genes are derived from the duplication of an ancestral precursor.

Aldehyde Oxidoreductases↗

First human experience with pulmonary vein isolation using a through-the-balloon circumferential ultrasound ablation system for recurrent atrial fibrillation.

BACKGROUND: Standard mapping and ablation of focal sources of atrial fibrillation are associated with very long procedure times and low efficacy. An anatomic approach to complete pulmonary vein isolation could overcome these limitations. METHODS AND RESULTS: Fifteen patients with atrial fibrillation refractory to medication underwent circumferential isolation of the pulmonary veins by using a novel catheter, with an ultrasound transducer (8-MHz) mounted near the tip, in a saline-filled balloon. Twelve atrial foci and/or atrial fibrillation triggers were identified in 9 patients (pulmonary vein locations: left upper, 3; right upper, 6; right middle, 1; right lower, 1; and left inferior, 1). In 5 patients, lesions were placed in the absence of any mapped triggers. Irrespective of trigger mapping, circumferential isolation of both upper pulmonary veins was attempted in all patients. The lower pulmonary veins were ablated when sinus rhythm activation mapping revealed evidence of a sleeve of atrial muscle in the vein. The median number of lesions per patient required to isolate 1 pulmonary vein was 4 (range, 1 to 29). After ablation, no evidence of narrowing was seen with repeat venography or follow-up computed tomography scan. After a mean follow-up of 35+/-6 weeks, 5 patients had recurrence of atrial fibrillation. Three responded to drugs that were previously ineffective, and 2 remained in atrial fibrillation. CONCLUSIONS: This novel ultrasound ablation system can successfully isolate multiple pulmonary veins. At early follow-up, this approach seems to be effective in preventing recurrent atrial fibrillation in a significant number of patients.

Adult↗

Effect of diet on serum albumin and hemoglobin adducts of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in humans.

2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is the most abundant heterocyclic amine formed in meat and fish during cooking and can be used as a model compound for this class of chemicals possibly involved in human carcinogenesis. Knowing the exposure to heterocyclic amines is important for establishing their role in human diseases. Serum albumin (SA) and globin (Gb) adducts were first tested as biomarkers of exposure to PhIP in male Fischer 344 rats given oral doses of 0.1, 0.5, 1 and 10 mg/kg. Blood samples were collected 24 hr after treatment and PhIP released from SA and Gb after acidic hydrolysis was analyzed by gas chromatography-mass spectrometry or liquid chromatography-tandem mass spectrometry. PhIP-SA and Gb adducts increased linearly with the dose. Studies on 35 volunteers with different dietary habits exhibited that diet was a major determinant in the formation of both adducts. PhIP-SA adducts were significantly higher in meat consumers than in vegetarians (6.7 +/- 1.6 and 0.7 +/- 0.3 fmol/mg SA; respectively, mean +/- SE; p = 0.04, Mann-Whitney U test). The Gb adduct pattern was quantitatively lower but paralleled SA (3 +/- 0.8 in meat consumers and 0.3 +/- 0.1 in vegetarians). PhIP-SA adducts were no different in smokers and in non-smokers. The results show for the first time that PhIP-blood protein adducts are present in humans not given the synthetic compound. Both biomarkers appear to be suitable for assessing dietary exposure and internal PhIP dose and may be promising tools for studying the role of heterocyclic amines in the etiology of colon cancer and other diseases.

Animals↗

Neuroadrenergic activation and response to dobutamine in congestive heart failure secondary to idiopathic dilated cardiomyopathy.

Detection of contractile reserve is important in heart failure patients. To determine if detection of contractile reserve is influenced by neuroadrenergic activation, we examined the relation between dobutamine stress echocardiography (DSE) findings and plasma norepinephrine levels (NE) at rest in 35 patients with nonischemic left ventricular (LV) dysfunction (New York Heart Association class >III in all; LV ejection fraction 0.27 +/- 0.5). Changes in global wall motion score (WMS), and separately in WMS of hypokinetic segments and akinetic segments, were analyzed. A patient was considered to be responsive to dobutamine if the change in global WMS was >/=4. Twenty-three patients were responsive and 12 were not responsive to dobutamine. Plasma NE and baseline heart rate were significantly higher in nonresponsive patients (p <0.001). Changes in global WMS and in hypokinetic segment WMS were inversely related to either plasma NE (r -0.68 and -0.67, respectively) or baseline heart rate (r -0.60 and -0.66, respectively). The change in akinetic segment WMS was related to plasma NE only (r -0.50). Changes in WMS were not related to age, diastolic and systolic LV volume, baseline global WMS, or number of akinetic segments at baseline. Plasma NE >602 pg/ml predicted a blunted or absent contractile reserve at DSE (sensitivity 92%; specificity 87%). Neuroadrenergic activation may influence contractile reserve found at DSE in patients with heart failure due to nonischemic LV dysfunction.

Adult↗

Presence of therapeutic drugs in the environment.

Therapeutic drugs can contaminate the environment because of metabolic excretion, improper disposal, or industrial waste. To assess the extent of this contamination, we listed drugs thought to be putative priority pollutants according to selected criteria, and measured them in Lombardy, Italy. Most drugs were measurable in drinking or river waters and sediments, suggesting that pharmaceutical products are widespread contaminants, with possible implications for human health and the environment.

Italy↗

Prospective randomized comparison of antiarrhythmic therapy versus first-line radiofrequency ablation in patients with atrial flutter.

BACKGROUND: Despite the high success rate of radiofrequency (RF) ablation, pharmacologic therapy is still considered the standard initial therapeutic approach for atrial flutter. OBJECTIVE: We prospectively compared the outcome at follow-up of patients with atrial flutter randomly assigned to drug therapy or RF ablation. METHODS: Patients with at least two episodes of symptomatic atrial flutter in the last four months were randomized to regimens of either antiarrhythmic drug therapy or first-line RF ablation. After institution of therapy, end points included recurrence of atrial flutter, rehospitalization and quality of life. RESULTS: A total of 61 patients entered the study, 30 of whom were randomized to drug therapy and 31 to RF ablation. After a mean follow-up of 21 +/- 11 months, 11 of 30 (36%) patients receiving drugs were in sinus rhythm, versus 25 of 31 (80%) patients who underwent RF ablation (p < 0.01). Of the patients receiving drugs, 63% required one or more rehospitalizations, whereas post-RF ablation, only 22% of patients were rehospitalized (p < 0.01). Following RF ablation, 29% of patients developed atrial fibrillation which was seen in 53% of patients receiving medications (p < 0.05). Sense of well being (pre-RF 2.0 +/- 0.3 vs. post-RF 3.8 +/- 0.5, p < 0.01) and function in daily life (pre-RF 2.3 +/- 0.4 vs. post-RF 3.6 +/- 0.6, p < 0.01) improved after ablation, but did not change significantly in patients treated with drugs. CONCLUSION: In a selected group of patients with atrial flutter, RF ablation could be considered a first-line therapy due to the better success rate and impact on quality of life, the lower occurrence of atrial fibrillation and the lower need for rehospitalization at follow-up.

Aged↗

Analysis of benzothiazole in Italian wines using headspace solid-phase microextraction and gas chromatography-mass spectrometry.

Benzothiazoles are a part of the molecular structure of a large number of natural products, biocides, drugs, food flavors, and industrial chemicals. They also appear in the environment mainly as a result of their production and use as rubber vulcanization accelerators. A new headspace solid-phase microextraction (HS-SPME) method for analysis of benzothiazole (BTH) in wine is described. This method is fast, inexpensive, and does not require solvents. The detection limit of BTH in wine was 45 ppt with linearity up to 100 ppb. The quantification of BTH is performed by the standard additions method and does not require the use of an internal standard. We have analyzed 12 wines from different grape varieties grown in several regions, using SPME extraction and gas chromatography-mass spectrometry (GC-MS) detection. Under these experimental conditions, benzothiazole was found in all wines analyzed. Concentration levels in samples varied from 0.24 microg/L (Vermentino) to 1.09 microg/L (Franciacorta).

Benzothiazoles↗

Modulation of vascular endothelial gene expression by physical training in patients with chronic heart failure.

BACKGROUND: Abnormalities of the skeletal muscle vasculature, such as endothelial dysfunction and reduced microvascular density, can be reversed by physical training in patients with chronic heart failure. The molecular mechanisms that mediate the beneficial effects of physical training on the vascular endothelium are unknown. METHODS: Endothelial nitric oxide synthase (eNOS) and vascular endothelial growth factor (VEGF) gene expression in the skeletal muscle, peak oxygen consumption (VO2) and calf peak reactive hyperemia were measured before and after 12 weeks of supervised physical training in 10 patients with chronic heart failure. Five patients with heart failure of similar severity who did not participate in the training program served as controls. RESULTS: The effects of physical training on eNOS and VEGF gene expression were heterogeneous. eNOS gene expression increased 3-4 fold in 4 patients while it remained constant in 6 patients. VEGF gene expression increased significantly in all patients who were not treated with beta-adrenergic blockade and remained constant in all patients who were treated with beta-adrenergic blockade. In contrast, physical training increased peak VO2 and calf peak reactive hyperemia in all patients. Mean peak VO2 increased from 13.13 +/- 2.21 to 16.19 +/- 2.69 ml/kg/min (p < 0.001) and calf peak reactive hyperemia increased from 19.7 +/- 2.3 to 29.6 +/- 4.0 ml*min(-1)*100 ml(-1) (p < 0.001). CONCLUSIONS: A supervised program of physical training that consistently enhanced peak VO2 and vascular reactivity in patients with chronic heart failure increased or left eNOS and VEGF gene expression unchanged in skeletal muscle. Changes in vascular endothelial gene expression may contribute to the benefits of training on vascular endothelial function but are not solely responsible for these benefits.

Aged↗

Analysis of some pesticides in water samples using solid-phase microextraction-gas chromatography with different mass spectrometric techniques.

A solid-phase microextraction (SPME)-GC procedure has been developed for the analysis of four selected pesticides (propanil, acetochlor, myclobutanil and fenoxycarb) in water samples. Mass spectrometry (MS) was used and two different instruments, a quadrupole MS system and an ion trap operating in the MS-MS mode, were compared. A Carbowax-divinylbenzene SPME fiber was used. The performances of the two GC-MS instruments were comparable in terms of linearity (in the range of 0.1-10 microg/l in water samples) and sensitivity (limits of detection were in the low ng/l range); the quadrupole MS instrument gave better precision than the ion trap MS-MS system, but generally the relative standard deviations for replicates were acceptable for both instruments (<15%). Specificity with these two instruments was comparable in the analysis of ground water samples. Recovery tests were made to assess the applicability of the SPME procedure in the quantitative analysis of contaminated groundwaters.

Carbamates↗

Central pulmonary artery lesions in chronic obstructive pulmonary disease: A transesophageal echocardiography study.

BACKGROUND: In patients with acute pulmonary embolism, transesophageal echocardiography (TEE) often reveals presumably thrombotic lesions within the central pulmonary arteries (CPAs). These CPA lesions, when found in patients with primary pulmonary hypertension, have been attributed to in situ thrombosis or atherosclerosis. We hypothesized that similar CPA lesions may also develop in patients with chronic obstructive pulmonary disease (COPD) in the absence of pulmonary embolism. METHODS AND RESULTS: We examined by TEE 25 patients with COPD and 27 control patients with left heart disease. None of the patients had previous pulmonary embolism or ileofemoral and popliteal vein thrombosis. By use of TEE, CPA lesions were found in 12 COPD patients (48%) and 2 control patients (7.4%) (P<0.01). When CPA lesions were subdivided into types 1 (protruding and mobile) and 2 (wall-adherent), type 1 lesions proved to be uncommon, being found within the pulmonary trunk in 12% and 3.7% of COPD and control patients, respectively (P=NS). Conversely, type 2 lesions, which were always localized in the right pulmonary artery, were frequent in COPD patients (36%) and rare in control patients (3.7%) (P<0.01). When available, helical CT and MR angiography confirmed TEE findings, supporting an atherosclerotic origin of type 2 lesions, which were different from typical thrombotic lesions. FEV(1)/FVC ratio, RV/TLC ratio, PaO(2), hematocrit value, and pulmonary artery systolic pressure were not significantly different in COPD patients with and without CPA lesions. At TEE, however, COPD patients with CPA lesions showed a larger size of the main and right pulmonary arteries. CONCLUSIONS: TEE often reveals CPA lesions in stable patients with COPD even in the absence of significant pulmonary hypertension and not in close relation with the severity of pulmonary dysfunction.

Aged↗

Biomonitoring of n-nitroso compounds, nitrite and nitrate in the urine of Egyptian bladder cancer patients with or without Schistosoma haematobium infection.

The excretion of nitrate, nitrite, apparent total N-nitroso compounds and volatile nitrosamines was measured in 24 hr urine from 61 Egyptians, divided into 4 groups: controls, Schistosoma haematobium-infected patients and bladder cancer patients with and without a history of schistosomal infection. Urinary nitrate in S. haematobium-infected patients was significantly higher than in the other 3 groups. Nitrite was below the detection limit of the method (</=0.015 microgram/mg creatinine) in all but one of the control samples. S. haematobium infection significantly increased urinary nitrite to 0.9 +/- 1.16 microgram/mg creatinine (mean +/- SD, p = 0. 001). In both bladder cancer groups, nitrite was about 20 times that in S. haematobium-infected patients without bladder cancer. Excretion of apparent total N-nitroso compounds paralleled that of nitrite. Overall, a good correlation was observed between these 2 variables (r = 0.71, p = 0.0001). N-nitrosodimethylamine was present in all the samples analyzed. S. haematobium infection significantly increased urinary N-nitrosodimethylamine level compared with that of controls (4.02 +/- 1.61 and 2.04 +/- 2.97 ng/mg creatinine, respectively, p = 0.01). Among cancer patients, N-nitrosodimethylamine was higher than in controls only in those with schistosomal infection. The presence of N-nitroso compounds and N-nitrosodimethylamine in the urine of S. haematobium-infected patients both before and after the development of cancer, and the observation that these compounds also occur in bladder cancer patients with no history of schistosomal infection, suggest that these compounds might have a role not only in the initiation of the carcinogenic process, but also in its progression.

Bacterial Infections↗