Trans-sulcal versus trans-parenchymal approach in supratentorial cavernomas. A multicentric experience.

OBJECTIVES: Cavernous malformations (CM) are low-flow vascular lesions that can cause significant symptoms and neurological deficits. Different intraoperative surgical approaches have been developed. Aim of the present investigation is the comparison between the trans-sulcal approach (TS) and the trans-parenchymal neuronavigation-assisted approach (TPN) in a surgical series from two neurosurgical centers. The technique and clinical outcomes are discussed, with a specific focus on seizure outcome. PATIENTS AND METHODS: Clinical and radiological data from two neurosurgical centers ("A. Gemelli" Hospital in Rome and A.O.U. Città della Salute e della Scienza in Turin) were retrospectively reviewed in order to evaluate the different outcome of TS and TPN approach for cavernous malformation treatment. RESULTS: A total of 177 patients underwent surgical intervention for supratentorial CM, 130 patients with TPN approach and 47 with TS approach. TS approach was associated with higher rate of seizure in early post-operative period both in epileptic patients (p < 0,001) and in patients without history of seizures before surgery (p = 0,002). Moreover, length of incision (p < 0,001), area of craniotomy (p < 0,001) and corticectomy (p < 0,001) were bigger in TS than in TPN approach. Brain contusion (p < 0,001) and fluid collection (p < 0,001) were more likely to be discovered after TS approach. CONCLUSIONS: TPN is a valuable approach for resection of CM. Minor complications are significantly lower in TPN approach when compared with TS approach. In addition, it is associated with lower rate of early post-operative seizure and shorter length of stay.

Evaluation by environmental monitoring of pesticide absorption in farm workers of 18 Italian tomato cultivations.

Tomato cultivation farms of Southern Italy were investigated in order to evaluate the general working conditions and the levels of exposure of farm workers to pesticides, during the mixing/loading and the application of pesticides on fields. Information on working modalities, personal protective equipment, etc. was collected using a questionnaire. Inhaling and cutaneous exposure levels were measured, and the estimated pesticide total absorbed dose was compared with Admissible Daily Intakes (ADIs). Field treatments were mainly carried out by using sprayers with open cab tractors, and, in 57.9 percent of cases, the pesticide mixture was manually prepared by mixing pesticides in a pail, often without using gloves (59.5 percent). The estimated pesticides absorbed doses varied in the range 0.56-2630.31 mg (mean value, 46.9 mg), and 20 percent of the measured absorbed doses exceeded ADIs. The findings obtained in the 18 examined farms show a worrying situation, suggesting the investigation of many more farms, so that a statistically significant picture of tomato cultivations in Southern Italy could be formed. Besides, the planning of training courses aimed to increase workers consciousness about health risks and how they can be prevented is advisable.

A study on the short-term effect of cafeteria diet and pioglitazone on insulin resistance and serum levels of adiponectin and ghrelin

The interaction between ghrelin and adiponectin is still controversial. We investigated the effect of cafeteria diet and pioglitazone on body weight, insulin resistance, and adiponectin/ghrelin levels in an experimental study on male Wistar rats. The animals were divided into four groups of 6 rats each, and received balanced chow with saline (CHOW-O) or pioglitazone (CHOW-P), or a cafeteria diet with saline (CAFE-O) or pioglitazone (CAFE-P). The chow/cafeteria diets were administered for 35 days, and saline/pioglitazone (10 mg·kg body weight-1·day-1) was added in the last 14 days prior to euthanasia. CAFE-O animals had a higher mean final weight (372.5 ± 21.01 g) than CHOW-O (317.66 ± 25.11 g, P = 0.017) and CHOW-P (322.66 ± 28.42 g, P = 0.035) animals. Serum adiponectin levels were significantly higher in CHOW-P (55.91 ± 20.62 ng/mL) than in CHOW-O (30.52 ± 6.97 ng/mL, P = 0.014) and CAFE-O (32.54 ± 9.03 ng/mL, P = 0.027) but not in CAFE-P. Higher total serum ghrelin levels were observed in CAFE-P compared to CHOW-P animals (1.65 ± 0.69 vs 0.65 ± 0.36 ng/mL, P = 0.006). Likewise, acylated ghrelin levels were higher in CAFE-P (471.52 ± 195.09 pg/mL) than in CHOW-P (193.01 ± 87.61 pg/mL, P = 0.009) and CAFE-O (259.44 ± 86.36 pg/mL, P = 0.047) animals. In conclusion, a cafeteria diet can lead to a significant weight gain. Although CAFE-P animals exhibited higher ghrelin levels, this was probably related to food deprivation rather than to a direct pharmacological effect, possibly attenuating the increase in adiponectin levels.

A study on the short-term effect of cafeteria diet and pioglitazone on insulin resistance and serum levels of adiponectin and ghrelin.

The interaction between ghrelin and adiponectin is still controversial. We investigated the effect of cafeteria diet and pioglitazone on body weight, insulin resistance, and adiponectin/ghrelin levels in an experimental study on male Wistar rats. The animals were divided into four groups of 6 rats each, and received balanced chow with saline (CHOW-O) or pioglitazone (CHOW-P), or a cafeteria diet with saline (CAFE-O) or pioglitazone (CAFE-P). The chow/cafeteria diets were administered for 35 days, and saline/pioglitazone (10 mg · kg body weight(-1) · day(-1)) was added in the last 14 days prior to euthanasia. CAFE-O animals had a higher mean final weight (372.5 ± 21.01 g) than CHOW-O (317.66 ± 25.11 g, P = 0.017) and CHOW-P (322.66 ± 28.42 g, P = 0.035) animals. Serum adiponectin levels were significantly higher in CHOW-P (55.91 ± 20.62 ng/mL) than in CHOW-O (30.52 ± 6.97 ng/mL, P = 0.014) and CAFE-O (32.54 ± 9.03 ng/mL, P = 0.027) but not in CAFE-P. Higher total serum ghrelin levels were observed in CAFE-P compared to CHOW-P animals (1.65 ± 0.69 vs 0.65 ± 0.36 ng/mL, P = 0.006). Likewise, acylated ghrelin levels were higher in CAFE-P (471.52 ± 195.09 pg/mL) than in CHOW-P (193.01 ± 87.61 pg/mL, P = 0.009) and CAFE-O (259.44 ± 86.36 pg/mL, P = 0.047) animals. In conclusion, a cafeteria diet can lead to a significant weight gain. Although CAFE-P animals exhibited higher ghrelin levels, this was probably related to food deprivation rather than to a direct pharmacological effect, possibly attenuating the increase in adiponectin levels.

Quantification of sirolimus and everolimus by immunoassay techniques: test specificity and cross-reactivity evaluation.

The possible cross-reactivity of immunoassays with structurally-related drugs was investigated. Innofluor Certican (FPIA) calibrators were measured by using IMx Sirolimus assay (MEIA) and MEIA Sirolimus calibrators were analysed by using FPIA Certican assay. Drug concentrations were measured in 95 and 100 samples from renal transplanted patients (RTP) on sirolimus or everolimus treatment by using immunoassays and LC/ESI-MSMS. A high cross-reactivity was found both for MEIA and FPIA. High correlation degrees, confirmed by the Bland-Altman and the Eksborg tests, were found between drug concentrations measured in real samples by both immunoassays (r = 0.909 and r = 0.970, respectively). LC/ESI-MSMS analysis of samples containing sirolimus showed no positivity for everolimus. Similarly, samples from patients on treatment with everolimus resulted negative as far as regards sirolimus. MEIA and FPIA could be considered mutually reliable and accurate alternatives for the specific-drug immunoassay. It should be noticed that in patients switching from one drug to the other unreal overestimation of the blood levels of the current administered immunosuppressant can occur.

Stability of sirolimus and everolimus measured by immunoassay techniques in whole blood samples from kidney transplant patients.

The measurement of blood concentration of immunosuppressive drugs is strongly recommended because of the narrow therapeutic range. An important aspect in the therapeutic monitoring of a drug is its possible degradation. This paper is aimed at investigating the stability of two widely-used immunosuppressants, sirolimus and everolimus. Short (storage at 30 degrees C for 3 or 7 days) and long term (storage at -20 degrees C for 0-90 days with a single freeze-thaw cycle) stability of sirolimus and everolimus in whole blood samples from kidney transplant patients were examined by using MEIA and FPIA. Sirolimus and everolimus samples stored at 30 degrees C in light for up to a week showed a decrement in concentration of 5.2 percent and 6.1 percent, respectively. Our findings on long term stability for both sirolimus and everolimus highlight the possibility of storing samples at -20 degrees C for up to 90 days, without the need to use lower storage temperatures. The results have important implications for patients living far from laboratories where drug concentration is measured or when the storing of blood samples is needed for pharmacokinetic studies.

[Algorithm validation for pesticide exposure risk evaluation by environmental monitoring data]. / Validazione di un algoritmo per la valutazione dei rischi da esposizione a pesticidi mediante dati di monitoraggio ambientale.

The risk evaluation related to the occupational exposure to hazardous substances can be performed either by analytical data coming from environmental and/or biological monitoring or by using models and mathematical algorithms. Models are often considered economically more advantageous, nevertheless, in order to assure their reliability, they need to be validated by objective monitoring data. A predictive model for the evaluation of risks due to the exposure to pesticides in agriculture was elaborated, and, for model validations, 20 tomato farms were examined. For each farm, information necessary to the risk evaluation by using the elaborated algorithm were collected and, simultaneously, an environmental monitoring for the evaluation of inhaling and cutaneous exposure was carried out. The potential risk was estimated by comparing analytical data from environmental monitoring with respect to ADI (Admissible Daily Intake) values, for each investigated pesticide. Then, the accordance between the potential risk and the risk given by the elaborated model was evaluated and an agreement of 85.6% was found, showing a substantial reliability of the proposed model.

[Risk evaluation of contact with pesticides in Naples municipality gardeners]. / Programma di valutazione del rischio da contatto con antiparassitari nei giardinieri del comune di Napoli.

Pesticide use still now is a remarkable risk for all cultivation operators, including farmers and flower-growing workers. Recently, pesticides use on ornamental plant has been demonstrated to be able to determine a risk extension to general population. Aim of the project was to elaborate and to apply a method for pesticides risk evaluation in ornamental plant cultivations, as to define workers exposure and its possible diffusion to not occupationally exposed populations. Main features of method will be sampling and analysis approach. The first will estimate air dispersion of pesticides in garden centre, skin and garment smarminess in nurserymen and leaf adhered amounts, in concomitance with treatment and periodically to estimate natural decay. The latter will characterize pesticides by means of different methods (liquid and gaseous chromatography, spectrophotometry and spectrometry). Final aim will also be to identify the most reliable analytic method, as concerns accuracy, sensitivity and specificity.

[Antiblastic drug exposure: statistical analysis of the data coming from environmental monitoring of a site devoted to drug production]. / Esposizione a farmaci antiblastici: analisi statistica dei dati di monitoraggio ambientale in una sala di allestimento dei farmaci.

An environmental monitoring strategy was carried out for the determination of surface concentrations of cyclophosphamide (CP), ifosfamide (IF) and 5-fluorouracil (5-FU) in a drug preparation room of an oncology ward. Analytes were determined by wipe tests, liquid-liquid extraction with diatomaceous earths and GC/MSMS or HPLC/UV analysis. The analysed 249 samples showed concentrations of CP, IF and 5-FU varying in the ranges 0.020-18.83, 0.100-26.96, 0.740-208.9 microg/dm2, respectively. It is noteworthy that the 9.3% (CP), 18.6% (IF) and 76.3% (5-FU) of the investigated surfaces showed high contamination levels, with analytes amount higher than 0.5 microg/dm2 and a progressive contamination decrement going from workbenches, floor, hood planes and other examined surfaces (interphone, telephone etc.). A significant correlation (rhos = 0.303, p = 0.001) between the measured analyte concentration and the analyte handled amount was found only in the case of IF, and a diffuse contamination (traces of all the three analytes) was found on all investigated surfaces, even when analytes were not been used during the sampling days.

[Combustion generated nanoparticles: mutagenicity and chemical reactivity]. / Nanoparticelle generate dalla combustione: mutagenicità e reattività.

Nanoparticles of organic carbon (NOC) are formed in combustion of hydrocarbon-rich fuels and have been detected in vehicle exhausts, suggesting their presence in urban atmospheres. Epidemiological studies showed that some causal relationships exist between particle concentration in the air and a wide range of health effects, but no toxicological studies are reported on the potential health risk of particles smaller than 4 nm. The present study investigated the mutagenicity and the reactivity of NOC collected in water samples from the exhausts of diesel and gasoline engines. Mutagenicity was tested following the Ames Test, with and without metabolic activation. Reactivity was investigated by using a new approach aimed to identify electrophilic agents present in the sample material, which if introduced into the organism, could interact with nucleophilic sites of biological macromolecules (DNA and proteins), forming adducts. Given the large number of nucleophilc sites within biological macromolecules, the complexity of NOC, and the inexact knowledge of its chemical structure, this approach was simplified by examining in vitro interactions between NOC particles and model peptides through LCIMS analyses of incubation mixtures The results indicate a high reactivity and, in several cases, the mutagenicity of NOCs, thus calling for suitable biomarkers assess NOC exposure associated with vehicle emissions.

Mono- and diiodocyclophosphamide as possible internal standards for cyclophosphamide quantification: characterization by ion trap multi-stage mass spectrometry and effects of iodine-chlorine substitution on the fragmentation pattern.

Hospital personnel involved in antineoplastic drug preparation and administration to patients are exposed to large amounts of these drugs. Labour legislation indicates the necessity of planning monitoring strategies aimed at prevention and/or reduction of drug exposure. Monitoring strategies consist of quantitative determinations of indicators, present in environmental and biological matrices. Among the antineoplastic drugs widely used, cyclophosphamide (CP) has been identified as a suitable indicator of potential exposure to mixtures of antineoplastic drugs. Many literature methods for quantitative analysis of CP involve either liquid (LC) or gas chromatography (GC) with mass spectrometry (MS), both of which require use of a suitable internal standard. The present work focuses on the synthesis of mono- and diiodocyclophosphamide (CPI and CPI(2)) to be used as internal standard. These compounds were analyzed by GC/EI-MS/MS and LC/ESI-MS(n) using ion trap mass spectrometry. The product ion mass spectra are interpreted in terms of proposed structures of fragment ions. Iodine-chlorine substitution resulted in a weakening of the carbon-halogen bond with a noteworthy influence on the ion fragmentation processes. The proposed suitability of CPI and CPI(2) as internal standards was based on similarities to CP as regards ionization and fragmentation processes. The results obtained suggest that CPI could be used as internal standard for CP quantification by LC/ESI-MS/MS, and CPI(2) for GC/EI-MS/MS analyses.

[Fumigation of soil and food: assessment of occupational exposure to methyl bromide]. / Fumigazione di terreni agricoli e derrate alimentari: la valutazione dell'esposizione professionale a bromuro di metile.

Innovative procedures were developed for the biological monitoring of workers exposed to methyl bromide, through the determination of biomarkers of exposure, such as bromide in serum, and of biomarkers of the biologically effective dose, such as haemoglobin adducts. The effectiveness of the developed techniques for the biological monitoring was tested through the analysis of blood samples from workers employed in soil fumigation.

Determination of urinary S-phenylmercapturic acid by liquid chromatography-tandem mass spectrometry.

Urinary S-phenylmercapturic acid (S-PMA) is considered a useful biomarker for the measurement of low levels of benzene exposure, related to occupational exposure, smoking habits or environmental pollution. S-PMA quantitative analysis requires highly sensitive and specific techniques and purification procedures, mainly based on liquid-liquid or solid-phase extraction, which result in time expensive analyses. A method was developed for the quantitative determination of S-PMA in urine by using a simple, reproducible and easily automatizable HPLC purification followed by LC/ESI-NI/MS2 analysis. In order to reduce the cost of the analysis, related to the use of expensive labeled standards, p-bromo-S-phenylmercapturic acid (p-Br-S-PMA) was synthesized, characterized and used as internal standard. The feasibility and efficacy of the proposed method were examined by constructing calibration curves in the range from 6.2 to 200 microg/l and data were analyzed in terms of linearity and statistical parameters. The detection limit, related to the purification of 1 ml urine sample is 5 microg/l. The method was applied to the analysis of 12 urine samples from smoker subjects non-occupationally exposed to benzene. S-PMA urinary levels ranged from 13.6 to >200 microg/l, suggesting a high influence of life style in the S-PMA excretion. The proposed analytical method is suitable for the biological monitoring of both smoker and non-smoker workers, occupationally exposed to benzene. By processing at least 2 ml of urine samples, the method appears to be also useful for the evaluation of benzene uptake due to the environmental pollution.

Mass spectrometric identification of a candidate biomarker peptide from the in vitro interaction of epichlorohydrin with red blood cells.

The reaction products of epichlorohydrin with human alpha- and beta- globins, obtained through in vitro incubation of these compounds and red blood cells, were determined by using reversed-phase high-performance liquid chromatography (RP-HPLC), electrospray ionization mass spectrometry and matrix-assisted laser desorption/ionization tandem mass spectrometry. The alpha-globin was much more reactive than the beta-globin. At low incubation ratios, approximating the order of magnitude of epichlorohydrin concentration as found in workplaces, the only modified peptide still detectable was the 62-90 belonging to the alpha-chain and carrying an incremental mass of 92 u on either His72 or His89. Given that the two peptides co-eluted in a single chromatographic peak during RP-HPLC separation, they could be chosen as suitable biomarkers for quantification in the setting up of a new methodology for the biological monitoring of persons occupationally exposed, replacing currently known procedures.

Changes in HIV-related risk behaviors following drug abuse treatment.

OBJECTIVES: To measure changes in HIV-related injection drug and sexual risk behaviors following drug treatment in a therapeutic community program. METHODS: We conducted a prospective cohort study of 261 drug users, randomly assigned to day or residential treatment. Participants were interviewed 2 weeks after entering treatment and 6, 12 and 18 months later (follow-up rate: 83%). RESULTS: Greater reductions in injection risk behaviors were associated with more time in treatment and the later waves of measurement. Wave was also associated with a reduction of sexual risk behavior. CONCLUSIONS: Drug abuse treatment was associated with a decrease in HIV-related risk behavior.

Determination of cyclophosphamide and ifosphamide in urine at trace levels by gas chromatography/tandem mass spectrometry.

A specific and sensitive method based on gas chromatography/tandem mass spectrometry with on-column injection was developed to quantify simultaneously cyclophosphamide and ifosphamide in urine by using trophosphamide as an internal standard. The urine samples were extracted with diethyl ether and derivatization was performed with heptafluorobutyric anhydride. The detection limits of cyclophosphamide and ifosphamide in urine samples were 0.1 and 0.5 ng ml(-1), respectively, with a signal-to-noise ratio of 3 : 1. The sensitivity, the specificity and the low cost of the instrumentation involved make this method suitable for economical analysis on a large scale, such as for the biological monitoring of occupational exposure to cyclophosphamide and ifosphamide in production plants and in hospitals during their pharmacological use.

A randomized trial comparing day and residential drug abuse treatment: 18-month outcomes.

Extending an earlier report of 6-month outcomes, this study reports 12- and 18-month follow-up data for clients (N = 188) entering a therapeutic community drug treatment program who were randomly assigned to day or residential treatment conditions. Outcomes included Addiction Severity Index composite scores and measures of depression, psychiatric symptoms, and social support. Both groups showed significant change over time. The pattern of change indicated decreased problem severity in the 1st 6 months and then maintenance of lowered problem severity. Comparisons between groups indicated greater improvement for residential treatment clients on social problems and psychiatric symptoms but no differences on the remaining outcomes. Although residential treatment may offer some specific advantages, the conclusion here is that improvement among day treatment clients was not significantly different from that of residential treatment clients.

Visicorrafia extramucosa con sutura absorbible sintética monofilamento en ratas Wistar / Extramucosal suture of the bladder using absorbable suture material: experimental study

El objetivo del trabajo es comparar los resultados con dos tipos de suturas en vesicorrafias realizadas en un plano.Se efectuó una vesicorrafia extramucosa en 48 ratas Wistar separadas en 2 grupos(n=24):en el primero con catgut 6-0 y en el segundo con polidioxanona(PDS)6-0.Cada grupo fue divido en 3 subgrupos según en momento del sacrificio:7,14 o 28 días luego de la cirugía.Se estudió la presencia de litiasis,alteraciones en los puntos de las suturas y la actividad inflamatoria,aguda y crónica.La litiasis ocurrió en los subgrupos a los 7 días(1),14 días(1),28 días(1)en el grupo catgut a los 14 días(3)y 28 días(1)La granulación,el edema y la presencia de células gigantes fue significativamente mayor en los subgrupos tratados con catgut.El número de macrógrafos y de polimorfonucleares fue mayor en el grupo suturado con catgut a los 7 y 14 días,como también el número de linfocitos a los 28 días.La polidioxanona produjo menor reacción inflamatoria aguda y crónica que el catgut

Visicorrafia extramucosa con sutura absorbible sintética monofilamento en ratas Wistar / Extramucosal suture of the bladder using absorbable suture material: experimental study

El objetivo del trabajo es comparar los resultados con dos tipos de suturas en vesicorrafias realizadas en un plano.Se efectuó una vesicorrafia extramucosa en 48 ratas Wistar separadas en 2 grupos(n=24):en el primero con catgut 6-0 y en el segundo con polidioxanona(PDS)6-0.Cada grupo fue divido en 3 subgrupos según en momento del sacrificio:7,14 o 28 días luego de la cirugía.Se estudió la presencia de litiasis,alteraciones en los puntos de las suturas y la actividad inflamatoria,aguda y crónica.La litiasis ocurrió en los subgrupos a los 7 días(1),14 días(1),28 días(1)en el grupo catgut a los 14 días(3)y 28 días(1)La granulación,el edema y la presencia de células gigantes fue significativamente mayor en los subgrupos tratados con catgut.El número de macrógrafos y de polimorfonucleares fue mayor en el grupo suturado con catgut a los 7 y 14 días,como también el número de linfocitos a los 28 días.La polidioxanona produjo menor reacción inflamatoria aguda y crónica que el catgut