Subacute corticobasal syndrome following internal carotid endarterectomy.

The present report is of two patients who, immediately after internal carotid endarterectomy, presented with unexplained hemiplegia, despite normal findings on repeated MRI scans, which secondarily evolved into homolateral subacute corticobasal syndrome (CBS), with asymmetrical hemispheric hypometabolism and evidence of dopaminergic denervation. This prompted us to propose an hypothesis of transient cerebral hypoxia arising during the surgical clamping period that might have provoked a prolonged or permanent functional lesion of the left hemisphere and basal ganglia, with no visible infarction on MRI but only synaptic rearrangement of the neural networks, thereby revealing or exacerbating a potentially preexisting silent impairment.

[Air and biomonitoring of occupational exposure to anesthetic gases in the health care workers of a large hospital in Milan]. / Il monitoraggio ambientale e biologico dell'esposizione professionale a gas anestetici presso le sale operatorie di un grande ospedale milanese.

In this study exposure to anesthetic gases in health care workers of a hospital of Milan was investigated. The evaluation focused on the period 2007-2010 and was performed by environmental monitoring (20 operating rooms and 54 samples) and biological monitoring (180 workers and 242 urine samples). Mean airborne exposure was 3:15 and 0.34 ppm for nitrogen protoxide (N2O) and sevorane; in end-of-exposure urine samples the concentration of N2O and hexafluoroisopropanol, metabolite of sevorane, were 4.85 mg/L and 0.21 mg/L, with 80 and 21% of values below the quantification limit. Sevorane monitoring exceeded or equaled the environmental limit value of 0.5 ppm and the biological exposure index in 17 and 11% of measures. There were no observed exceedances of the limit for N2O. The anesthetist and scrub nurse were tasks with greater exposure. There was a significant correlation between airborne halogenated gases and urinary hexafluoroisopropanol. The results of this study indicates that further efforts are needed to improve the hygienic conditions in the investigated hospital.

Atrial fibrillation is associated with hypermethylation in human left atrium, and treatment with decitabine reduces atrial tachyarrhythmias in spontaneously hypertensive rats.

Atrial fibrillation (AF) is the most common cardiac arrhythmia. As the molecular mechanisms underlying the pathology are largely unknown, this cardiac arrhythmia remains difficult to treat. To identify specific molecular actors involved in AF, we have performed a transcriptomic analysis on left atrium (LA) from patients with valvular heart disease with or without AF. We showed that 1627 genes had altered basal expression level in LA tissue of AF patients compared with the control group. The significantly enriched gene ontology biological process "anatomical structure morphogenesis" contained the highest number of genes in line with changes in structure that occur when the human heart remodels following AF development (ie, LA dilatation and interstitial fibrosis). We then focused the study on Pitx2 (paired-like homeodomain 2), being the most altered transcription factor in LA from AF patients and from which compelling evidence have indicated that its reduced expression can be considered as a marker for the disease. In addition, its expression was inversely correlated with LA size. We demonstrated that AF is associated with Pitx2 promoter hypermethylation both in humans and arrhythmic aging spontaneously hypertensive rats. Chronic administration of a DNA methylation inhibitor (ie, 5-Aza-2'-deoxycitidine) improved ECG arrhythmic profiles and superoxide dismutase activities and reduced fibrosis in the left ventricle of spontaneously hypertensive rats. Taken together, these data support the notion that AF is associated with epigenetic changes in LA and provide a proof-of-concept that hypomethylating agents have to be considered in the treatment of atrial arrhythmias.

[Cancer and fecundity]. / Cancer et fécondité.

The overall increase in relative survival rates of adult and childhood cancer patients is related to improved chemotherapy and radiotherapy treatment protocols. However, this success is tempered by gonadotoxic effects and uterine damage. The reduced fertility and possible premature menopause can have a profound impact on patients self-esteem and quality of life. Consequently, preservation of fertility or treatments to protect the ovarian function, become a more relevant issue. Advances in assisted reproduction techniques have focused on the following: embryo cryopreservation which is restricted by time and constrains such as, sexual maturity and the presence of a stable partner. Cryopreservation of immature ovarian tissue, the most promising option, with restoration of natural fertility following auto-transplantation or maturation of oocytes in vitro in combination with assisted reproduction.

[Urinary MTBE as biological marker of exposure to traffic exhaust fumes]. / Valutazione di MTBE urinario come indicatore biologico di esposizione a traffico autoveicolare.

Methyl tert-butyl ether (MTBE) is an oxygenated compound added to Italian fuel in quantity of about 3% v/v. In the present study the excretion of urinary MTBE (U-MTBE) was evaluated as biomarker of exposure to traffic exhaust fumes. With this aim 127 Milan urban policemen, working as traffic wardens, were investigated. Spot urine samples were obtained prior to and at the end of the work shift, in different seasons. Median U-MTBE varied from 74 to 164 ng/L (range 60-657 ng/L). Comparing the pre-shift and end-shift samples an increase of about 14% in the U-MTBE level during the workshift was observed. An influence of the different seasons was observed, with lower values in spring and higher values in winter. Smoking did not affect the excretion of U-MTBE. The results of this study suggest that U-MTBE is a sensitive and specific marker for the assessment of exposure to traffic exhaust fumes.

Determination of hexafluoroisopropanol, a sevoflurane urinary metabolite, by 9-fluorenylmethyl chloroformate derivatization.

A reversed-phase HPLC method with fluorescence detection for the quantification of hexafluoroisopropanol (HFIP) in urine is presented. HFIP, a metabolite of the inhalation anesthetic sevoflurane, is excreted mainly in urine as glucuronic acid conjugate. After enzymatic hydrolysis of the glucuronate, primary amino groups of interferent urinary compounds are blocked by reaction with o-phthalic dicarboxaldehyde and 3-mercaptopropionic acid, followed by labeling of HFIP with 9-fluorenylmethyl chloroformate. The derivatization reaction proceeds in a water-acetonitrile (1:1) solution at room temperature with a borate buffer of pH 12.5 as a catalyst. A stable fluorescent derivative of HFIP is formed within 5 min. The HFIP-FMOC derivative is separated by reversed-phase chromatography with isocratic elution on an octadecyl silyl column (33x4.6 mm, 3 microm) and guard column (20x4.0 mm, 40 microm), at 35 degrees C, and detected by fluorescence detection at an excitation wavelength of 265 nm and an emission wavelength of 311 nm. The method detection limit is 40 pg, per 10-microl injection volume, corresponding to 16 microg/l of HFIP in urine. The among-series relative standard deviation is <6% at 200 microg/l (n=6). As a preliminary application, the method was used to detect HFIP concentration in the urine of two volunteers exposed for 3 h to an airborne concentration of sevoflurane in the order of 2 ppm.

[Magnetic resonance imaging early after acute myocardial infarction. A visual analysis of myocardial perfusion based on a 17 segment model]. / Imagerie par résonance magnétique en postinfarctus immédiat. Analyse visuelle de la perfusion myocardique sur un modèle à 17 segments.

Magnetic resonance imaging allows an accurate calculation of the left ventricular ejection fraction and left ventricular volumes. Additionally, it makes possible to assess myocardial perfusion after gadolinium chelate injection. Late after the injection, the presence of a myocardial hyper-enhancement can be visualized. The present study has used the 17 segment standardized nomenclature for tomographic imaging of the heart as recommended for all cardiac imaging modalities. Sixty nine patients were studied after a revascularised myocardial infarction. All patients had Timi grade 3 flow in the infarct-related artery after therapy. Regional and global function was studied using cine MR short axis slices. The gadolinium chelate first pass was scored using a 5 level scale reflecting the transmural extent of the segmental myocardial enhancement. The delayed enhancement due to gadolinium accumulation in the myocardium 10 min post injection was scored in the same manner. Left ventricular ejection fraction was 51 +/- 13%. Segmental thickening parameters (systolic thickness, absolute thickening and relative thickening) appeared statistically related to the hypoperfusion and delayed enhancement scores. Absolute myocardial thickening varied from 4.8 +/- 2.7 mm in the myocardial segments free of any delayed enhancement to 2.4 +/- 2.1 mm in segments presenting with a transmural extent of the delayed hyper-enhancement. Scores obtained after gadolinium injection were also well correlated with the global left ventricular function (r = 0.65, p < 0.01 for late enhancement). Magnetic resonance imaging of the heart allows a precise characterisation of revascularised myocardium which makes this technique very attractive for evaluating the treatments designed to improve myocardial microperfusion.

[Value of cervical plain radiography in unconscious trauma patient]. / Intérêt des radiographies standard du rachis cervical chez le traumatisé inconscient.

INTRODUCTION: The aim of this study was to evaluate the diagnostic value of cervical spine standard radiographs, performed in emergency, and compared with entire cervical helical CT with multiplanar reconstructions as reference. STUDY DESIGN: Open prospective study. PATIENTS AND METHODS: We conducted a six months prospective study including all patients over 15 years of age and unconscious (Glasgow Coma Scale < or = 12). Each patient underwent standard radiographs as well as helical CT of the entire cervical spine. Three senior surgeons and one senior radiologist evaluated the standard radiographs quality. The interpretation was performed by 7 different groups of judges. Two radiologists interpreted the helical CT. For each group, the sensibility, the specificity and the count of correct diagnosis for the standard radiographs were evaluated. The results of the correct diagnosis of each group were then compared to determine the most performant group. RESULTS: Fifty-one patients were included. Helical CT diagnosed spine injuries in 11 patients. The quality of standard radiographs was poor with less than 10% judged correct and 90% of the C7-D1 junction not visible. In the best group (radiologist), the sensibility was 50%, the specificity was 85% and the count of correct diagnosis was 78%. For the correct diagnosis, senior radiologist was significantly better than anaesthetist students, radiologist students and emergency physicians. CONCLUSION: The diagnostic value of standard radiographs was weak whatever the physician. Therefore, helical CT of the entire cervical spine is absolutely necessary and must be performed during the initial evaluation, if the haemodynamic conditions are required.

[The biological monitoring of occupational exposure to anesthetic gas and vapors: the determination of nitrogen protoxide, halothane and isoflurane in the urine]. / Monitoraggio biologico dell'esposizione professionale a gas e vapori anestetici: determinazione di protossido d'azoto, alotano e isofluorano nell'urina.

A gas-chromatographic method has been developed for measuring urinary nitrous oxide, halothane and isoflurane concentrations. A volume of head-space gases obtained from biological samples is analyzed by ECD-GC on a steel column (2 mm ID) serially packed with Porapak Q (1.2 m) and MS-5A (0.30 m), operated at 160 degrees C. The detection limit (ranging from 0.03 micrograms/l for halothane to 1 microgram/l for nitrous oxide), between-day precision (CV < 6%) and working linear range (up to 100 micrograms/l for halothane and 2000 micrograms/l for nitrous oxide) were determined. A two-year experience in biological monitoring of occupationally exposed surgical staff with the proposed method is reported and confounding factors are discussed. The method is easy to perform, free from interferences and suitable for use in routine analysis in toxicological laboratories.

[Biological monitoring of environmental benzene exposure in traffic wardens]. / Monitoraggio biologico dell'esposizione ambientale a benzene in addetti alla vigilanza urbana.

Vehicle exhausts are a well known source of aromatic hydrocarbon pollution in urban environments. The paper reports the results of environmental and biological monitoring of benzene exposure in traffic wardens carried out over a 5-hour workshift. Subjects (n = 131) were grouped according to smoking habits and job task as follows: group (A) 52 nonsmoking office workers, (B) 43 nonsmoking outdoor workers, subdivided into (B1) 36 working on foot and (B2) 7 cyclists; (C) 20 smokers office workers, (D) 16 smokers outdoor workers, subdivided into (D1) 11 working on foot and (D1) 5 cyclists. The median indoor environmental benzene concentration (26 micrograms/m3, n = 50) was significantly lower than the outdoor concentration (45 micrograms/m3, n = 43) (p < 0.01); median exposure value of cyclists was 78 micrograms/m3 (n = 12). For biological monitoring, urinary excretion of trans,transmuconic acid was determined in spot samples collected at 7:30 h (MAit) and 12:30 h (MAft). The MAftA median value (63 micrograms/l, range 2-242 micrograms/l) was not statistically different from MAftB (74 micrograms/l, range 15-216 micrograms/l), while the MAftB2 value of 96 micrograms/l was higher than both MAftB1 (71 micrograms/l) and MAftA. In group (B) there was a relationship between airborne benzene levels and MAftB excretion (y = 17.2 + 1.1x, r = 0.62, n = 35, p < 0.01). The influence of smoking on urinary MA excretion was studied by comparing the results obtained in all nonsmokers (AB) with smokers (CD). MAftCD (192 micrograms/l) was significantly higher than MAftAB (69 micrograms/l) (p < 0.01). In smokers, statistically significant relationships were observed between urinary excretion of MAft (y, microgram/l) and cotinine (x, microgram/l) (y = 83 + 0.08x, r = 0.73, n = 23, p < 0.01), and smoking (x, number cigarettes/day) (y = 87.4 + 4.4x, r = 0.53, n = 29, p < 0.01). Comparison between MAft and MAit median excretion values, calculated for each of the 6 exposure groups, showed that MAft was always higher than the corresponding MAit value. A rough estimate of the total dose of benzene ("index of exposure", EI) inhaled by each subject during the 5-hour working shift as a consequence of air pollution and smoking was also made. Considering the entire group of subjects, a significant association was observed between EI and MAft values (y = 43.4 + 0.39x, r = 0.65, n = 104, p < 0.01). Individual values of MA it were correlated with MAft according to the equation y = 43.6 + 0.82x (r = 0.62, n = 105; p < 0.01) and were also positively associated with EI values (y = 42.3 + 0.20x; r = 0.55; n = 74; p < 0.01). In conclusion, the results suggest that the measurement of urinary MA excretion is a poor indicator for assessing environmental benzene exposure at levels below 100 micrograms/m3, such as those seen in this study; MA can however be reliably used as a biomarker for higher exposures such as those, for example, due to smoking.

[Application of high-pressure liquid chromatography in the analysis of urinary metabolites of aromatic solvents]. / Applicazioni della cromatografia liquida ad alte prestazioni nell'analisi dei metaboliti urinari dei solventi aromatici.

The introduction of HPLC methods in industrial toxicology represents a valuable tool for the routine monitoring of workers occupationally exposed to aromatic solvents. The HPLC method described here permits the simultaneous determination of metabolites of ethylbenzene, styrene, toluene, xylene isomers, benzene, phenol and cresol isomers in diluted urine samples. Pretreatment of urine samples with steam distillation is necessary only for determination of phenol and cresols because of their low concentrations. A comparison between a GLC and the HPLC procedure for mandelic and phenylglyoxylic acids confirmed the satisfactory performance of the HPLC method.

Aluminum determination in biological fluids and dialysis concentrates via chelation with 8-hydroxyquinoline and solvent extraction/fluorimetry.

We describe a simple, rapid, and sensitive fluorescence method for measurement of aluminum (Al) in human biological fluids, in dialysis solutions, and in tap water, which uses 8-hydroxyquinoline for ion chelation. The fluorescence intensity of the toluene-extracted metal chelate (excitation wavelength, 380 nm; emission wavelength, 504 nm) remains unchanged for over 48 h at room temperature. Fluorescence intensity is a linear function of the concentration of Al in the 2-1000 microg/L range with detection limits of 0.7-2 microg/L. A large excess of other ions normally found in biological fluids does not interfere in Al determination. The method developed was successfully used in assaying Al in serum and urine of reference subjects, in serum samples from patients undergoing long-term dialysis, and in dialysis solutions. Al concentrations, measured by this fluorimetric procedure, were compared with those obtained by Zeeman graphite-furnace atomic absorption spectrometry. A correlation coefficient of 0.98 was obtained. The proposed method could be used for routine analysis in clinical laboratories for accurate determination of aluminum in aqueous or biological fluids.

Liquid chromatography of urinary porphyrins for the biological monitoring of occupational exposure to porphyrinogenic substances.

Very sensitive and precise analytical methods for measuring total porphyrin excretion and the relative amounts of different porphyrins in urine are required in order to monitor the biological effects of porphyrinogenic substances in workers and the general population. Many analytical steps of a HPLC method for measuring porphyrins as methyl esters in urine have been perfected. Sensitivity is 0.1 microgram/1 for each type of porphyrin, and average recovery is 92% in the range of 50-450 micrograms/liter porphyrins. The coefficient of variation is 3.4% within a series and 12.5% between series. Chemical oxidation before analysis and appropriate storing of the samples are the key points in achieving high quality results. The urinary excretion of porphyrins in healthy male workers varies within the range 21 to 161 micrograms/liter (95% limits of a group of 78 subjects). Concomitant factors, like drug use or liver disorders, were found to alter urinary porphyrin excretion. The proposed method permits the detection of extremely small alterations in porphyrin excretion resulting from occupational exposure to industrial chemicals such as, for example, mild coproporphyrinuria or early stages of chemical porphyria induced by polyhalogenated arylhydrocarbons.

Gas chromatography-electron-capture detection of urinary methylhippuric acid isomers as biomarkers of environmental exposure to xylene.

Methylhippuric acid isomers (MHAs), urinary metabolites of xylenes, were determined, after clean-up by C18-SPE and esterification with hexafluoroisopropanol and diisopropylcarbodiimide, by GC with ECD detection, on an SPB-35 capillary column (30 m, 0.32 mm I.D., 0.25 microm film thickness, beta = 320). S-benzyl-mercapturic acid was used for internal standardization. Chromatographic conditions were: oven temperature 162 degrees C, for 14.2 min; ramp by 30 degrees C/min to 190 degrees C, for 3.5 min; ramp by 30 degrees C/min to 250 degrees C, for 4 min; helium flow rate: 1.7 ml/min; detector and injector temperature: 300 degrees C. The sample (1 microl) was injected with a split injection technique (split ratio 5:1). MHA recovery was >95% in the 0.5-20 micromol/l range; the limit of detection was <0.25 micromol/l; day-to-day precision, at 2 micromol/l, was Cv<10%. Urinary MHAs were determined in subjects exposed to different low-level sources of xylenes: (a) tobacco smoking habit and (b) BTX urban air pollution (airborne xylene ranging from 0.1 to 3.7 micromol/m3). Study (a) showed a significant difference between urinary MHA median excretion values of nonsmokers and smokers (4.6 micromol/l vs. 8.1 micromol/l, p<0.001). Study (b) revealed a significant difference between indoor workers and outdoor workers (4.3 micromol/l vs. 6.9 micromol/l, p<0.001), and evidenced a relationship between MHAs (y, micromol/mmol creatinine) and airborne xylene (x, micromol/m3) (y = 0.085+0.34x; r = 0.82, p<0.001, n = 56). Proposed biomarkers could represent reliable tools to study very low-level exposure to aromatic hydrocarbons such as those observed in the urban pollution due to vehicular traffic or in indoor air quality evaluation.