The PEDRO (Pocketable Electronic Devices in Radiation Oncology) project: how clinical practice is changing among young radiation oncologists.

Purpose. To evaluate the impact of mobile devices and apps on the daily clinical activity of young radiation oncologists. Methods. A web-based questionnaire was sent to 382 young (≤40 years) members of the Italian Association of Radiation Oncology (AIRO). The 14 items investigated the diffusion of mobile devices (smartphones and/or tablets), their impact on daily clinical activity, and possible differences perceived by the participants over time. Results. A total of 158 questionnaires were available for statistical evaluation (response rate 41%). Up to 75% of respondents declared they used an electronic device during their clinical activity. Conversely, 82% considered the impact of smartphones/tables on daily practice low to moderate. Daily device use increased significantly from 2009 to 2012, with high daily use rates rising from 5% to 39.9%. Fulfillment of professional needs was declared by less than 42% of respondents and compliance with app indications by 32%. Almost all physicians desired in 2012 a comprehensive website concerning a variety of apps covering radiation oncologists' needs. Conclusions. Mobile devices are widely used by young Italian radiation oncologists in their daily clinical practice, while the indications so obtained are not always followed. Nevertheless, it would be important to verify the consistency of information found within apps, in order to avoid potential errors that might be detrimental to patients.

Nation-wide survey on radiation doses in diagnostic and interventional radiology in Switzerland in 1998.

A nation-wide survey on radiation doses in diagnostic and interventional radiology was conducted in Switzerland in 1998 aiming at establishing their collective radiological impact on the Swiss population. The study consisted on the one hand of surveying the frequency of more than 250 types of examinations, covering conventional radiology, mammography, fluoroscopy, angiography, interventional radiology, CT, bone densitometry, conventional tomography and dental radiology. On the other hand, for each type of examination the associated patient dose was established by modeling. The results of this study show that about 9.5 million diagnostic and interventional examinations are performed annually in Switzerland (1.34 per caput) and that the associated annual collective dose is of the order of 7100 person.Sv (1.0 mSv per caput). Switzerland is similar to other European countries in terms of the frequency of examinations and the collective dose.

Fast quantification of ten psychotropic drugs and metabolites in human plasma by ultra-high performance liquid chromatography tandem mass spectrometry for therapeutic drug monitoring.

A sensitive and selective ultra-high performance liquid chromatography (UHPLC) tandem mass spectrometry (MS/MS) method was developed for the fast quantification of ten psychotropic drugs and metabolites in human plasma for the needs of our laboratory (amisulpride, asenapine, desmethyl-mirtazapine, iloperidone, mirtazapine, norquetiapine, olanzapine, paliperidone, quetiapine and risperidone). Stable isotope-labeled internal standards were used for all analytes, to compensate for the global method variability, including extraction and ionization variations. Sample preparation was performed by generic protein precipitation with acetonitrile. Chromatographic separation was achieved in less than 3.0min on an Acquity UPLC BEH Shield RP18 column (2.1mm×50mm; 1.7μm), using a gradient elution of 10mM ammonium formate buffer pH 3.0 and acetonitrile at a flow rate of 0.4ml/min. The compounds were quantified on a tandem quadrupole mass spectrometer operating in positive electrospray ionization mode, using multiple reaction monitoring. The method was fully validated according to the latest recommendations of international guidelines. Eight point calibration curves were used to cover a large concentration range 0.5-200ng/ml for asenapine, desmethyl-mirtazapine, iloperidone, mirtazapine, olanzapine, paliperidone and risperidone, and 1-1500ng/ml for amisulpride, norquetiapine and quetiapine. Good quantitative performances were achieved in terms of trueness (93.1-111.2%), repeatability (1.3-8.6%) and intermediate precision (1.8-11.5%). Internal standard-normalized matrix effects ranged between 95 and 105%, with a variability never exceeding 6%. The accuracy profiles (total error) were included in the acceptance limits of ±30% for biological samples. This method is therefore suitable for both therapeutic drug monitoring and pharmacokinetic studies.

Radiation protection in digestive endoscopy: European Society of Digestive Endoscopy (ESGE) guideline.

This article expresses the current view of the European Society of Gastrointestinal Endoscopy (ESGE) about radiation protection for endoscopic procedures, in particular endoscopic retrograde cholangiopancreatography (ERCP). Particular cases, including pregnant women and pediatric patients, are also discussed. This Guideline was developed by a group of endoscopists and medical physicists to ensure that all aspects of radiation protection are adequately dealt with. A two-page executive summary of evidence statements and recommendations is provided. The target readership for this Guideline mostly includes endoscopists, anesthesiologists, and endoscopy assistants who may be exposed to X-rays during endoscopic procedures.

Determination of picogram levels of midazolam, and 1- and 4-hydroxymidazolam in human plasma by gas chromatography-negative chemical ionization-mass spectrometry.

Midazolam is a widely accepted probe for phenotyping cytochrome P4503A. A gas chromatography-mass spectrometry (GC-MS)-negative chemical ionization method is presented which allows measuring very low levels of midazolam (MID), 1-OH midazolam (1OHMID) and 4-OH midazolam (4OHMID), in plasma, after derivatization with the reagent N-tert-butyldimethylsilyl-N-methyltrifluoroacetamide. The standard curves were linear over a working range of 20 pg/ml to 5 ng/ml for the three compounds, with the mean coefficients of correlation of the calibration curves (n = 6) being 0.999 for MID and 1OHMID, and 1.0 for 4OHMID. The mean recoveries measured at 100 pg/ml, 500 pg/ml, and 2 ng/ml, ranged from 76 to 87% for MID, from 76 to 99% for 1OHMID, from 68 to 84% for 4OHMID, and from 82 to 109% for N-ethyloxazepam (internal standard). Intra- (n = 7) and inter-day (n = 8) coefficients of variation determined at three concentrations ranged from 1 to 8% for MID, from 2 to 13% for 1OHMID and from 1 to 14% for 4OHMID. The percent theoretical concentrations (accuracy) were within +/-8% for MID and 1OHMID, within +/-9% for 4OHMID at 500 pg/ml and 2 ng/ml, and within +/-28% for 4OHMID at 100 pg/ml. The limits of quantitation were found to be 10 pg/ml for the three compounds. This method can be used for phenotyping cytochrome P4503A in humans following the administration of a very low oral dose of midazolam (75 microg), without central nervous system side-effects.

Clear detection of ADIPOQ locus as the major gene for plasma adiponectin: results of genome-wide association analyses including 4659 European individuals.

OBJECTIVE: Plasma adiponectin is strongly associated with various components of metabolic syndrome, type 2 diabetes and cardiovascular outcomes. Concentrations are highly heritable and differ between men and women. We therefore aimed to investigate the genetics of plasma adiponectin in men and women. METHODS: We combined genome-wide association scans of three population-based studies including 4659 persons. For the replication stage in 13795 subjects, we selected the 20 top signals of the combined analysis, as well as the 10 top signals with p-values less than 1.0 x 10(-4) for each the men- and the women-specific analyses. We further selected 73 SNPs that were consistently associated with metabolic syndrome parameters in previous genome-wide association studies to check for their association with plasma adiponectin. RESULTS: The ADIPOQ locus showed genome-wide significant p-values in the combined (p=4.3 x 10(-24)) as well as in both women- and men-specific analyses (p=8.7 x 10(-17) and p=2.5 x 10(-11), respectively). None of the other 39 top signal SNPs showed evidence for association in the replication analysis. None of 73 SNPs from metabolic syndrome loci exhibited association with plasma adiponectin (p>0.01). CONCLUSIONS: We demonstrated the ADIPOQ gene as the only major gene for plasma adiponectin, which explains 6.7% of the phenotypic variance. We further found that neither this gene nor any of the metabolic syndrome loci explained the sex differences observed for plasma adiponectin. Larger studies are needed to identify more moderate genetic determinants of plasma adiponectin.

Determination of meropenem in plasma and filtrate-dialysate from patients under continuous veno-venous haemodiafiltration by SPE-LC.

Meropenem, a carbapenem antibiotic displaying a broad spectrum of antibacterial activity, is administered in Medical Intensive Care Unit to critically ill patients undergoing continuous veno-venous haemodiafiltration (CVVHDF). However, there are limited data available to substantial rational dosing decisions in this condition. In an attempt to refine our knowledge and propose a rationally designed dosage regimen, we have developed a HPLC method to determine meropenem after solid-phase extraction (SPE) of plasma and dialysate fluids obtained from patients under CVVHDF. The assay comprises the simultaneous measurement of meropenem's open-ring metabolite UK-1a, whose fate has never been studied in CVVHDF patients. The clean-up procedure involved a SPE on C18 cartridge. Matrix components were eliminated with phosphate buffer pH 7.4 followed by 15:85 MeOH-phosphate buffer pH 7.4. Meropenem and UK-1a were subsequently desorbed with MeOH. The eluates were evaporated under nitrogen at room temperature (RT) and reconstituted in phosphate buffer pH 7.4. Separation was performed at RT on a Nucleosil 100-5 microm C18 AB cartridge column (125 x 4 mm I.D.) equipped with a guard column (8 x 4 mm I.D.) with UV-DAD detection set at 208 nm. The mobile phase was 1 ml min(-1), using a step-wise gradient elution program: %MeOH/0.005 M tetrabutylammonium chloride pH 7.4; 10/90-50/50 in 27 min. Over the range of 5-100 microg ml(-1), the regression coefficient of the calibration curves (plasma and dialysate) were >0.998. The absolute extraction recoveries of meropenem and UK-1a in plasma and filtrate-dialysate were stable and ranged from 88-93 to 72-77% for meropenem, and from 95-104 to 75-82% for UK-1a. In plasma and filtrate-dialysate, respectively, the mean intra-assay precision was 4.1 and 2.6% for meropenem and 4.2 and 3.7% for UK-1a. The inter-assay variability was 2.8 and 3.6% for meropenem and 2.3 and 2.8% for UK-1a. The accuracy was satisfactory for both meropenem and UK-1a with deviation never exceeding 9.0% of the nominal concentrations. The stability of meropenem, studied in biological samples left at RT and at +4 degrees C, was satisfactory with < 5% degradation after 1.5 h in blood but reached 22% in filtrate-dialysate samples stored at RT for 8 h, precluding accurate measurements of meropenem excreted unchanged in the filtrate-dialysate left at RT during the CVVHDF procedure. The method reported here enables accurate measurements of meropenem in critically ill patients under CVVHDF, making dosage individualisation possible in such patients. The levels of the metabolite UK-1a encountered in this population of patients were higher than those observed in healthy volunteers but was similar to those observed in patients with renal impairment under hemodialysis.

Adaptive statistical iterative reconstruction reduces patient radiation dose in neuroradiology CT studies.

INTRODUCTION: Adaptive statistical iterative reconstruction (ASIR) can decrease image noise, thereby generating CT images of comparable diagnostic quality with less radiation. The purpose of this study is to quantify the effect of systematic use of ASIR versus filtered back projection (FBP) for neuroradiology CT protocols on patients' radiation dose and image quality. METHODS: We evaluated the effect of ASIR on six types of neuroradiologic CT studies: adult and pediatric unenhanced head CT, adult cervical spine CT, adult cervical and intracranial CT angiography, adult soft tissue neck CT with contrast, and adult lumbar spine CT. For each type of CT study, two groups of 100 consecutive studies were retrospectively reviewed: 100 studies performed with FBP and 100 studies performed with ASIR/FBP blending factor of 40 %/60 % with appropriate noise indices. The weighted volume CT dose index (CTDIvol), dose-length product (DLP) and noise were recorded. Each study was also reviewed for image quality by two reviewers. Continuous and categorical variables were compared by t test and free permutation test, respectively. RESULTS: For adult unenhanced brain CT, CT cervical myelography, cervical and intracranial CT angiography and lumbar spine CT both CTDIvol and DLP were lowered by up to 10.9 % (p < 0.001), 17.9 % (p = 0.005), 20.9 % (p < 0.001), and 21.7 % (p = 0.001), respectively, by using ASIR compared with FBP alone. Image quality and noise were similar for both FBP and ASIR. CONCLUSION: We recommend routine use of iterative reconstruction for neuroradiology CT examinations because this approach affords a significant dose reduction while preserving image quality.

A highly sensitive LC-tandem MS assay for the measurement in plasma and in urine of salbutamol administered by nebulization during mechanical ventilation in healthy volunteers.

The new-generation nebulizers are commonly used for the administration of salbutamol in mechanically ventilated patients. The different modes of administration and new devices have not been compared. We developed a liquid chromatography-tandem mass spectrometry method for the determination of concentrations as low as 0.05 ng/mL of salbutamol, corresponding to the desired plasma concentration after inhalation. Salbutamol quantification was performed by reverse-phase HPLC. Analyte quantification was performed by electrospray ionization-triple quadrupole mass spectrometry using selected reaction monitoring detection ESI in the positive mode. The method was validated over concentrations ranging from 0.05 to 100 ng/mL in plasma and from 0.18 to 135 ng/mL in urine. The method is precise, with mean inter-day coefficient of variation (CV%) within 3.1-8.3% in plasma and 1.3-3.9% in urine, as well as accurate. The proposed method was found to reach the required sensitivity for the evaluation of different nebulizers as well as nebulization modes. The present assay was applied to examine whether salbutamol urine levels, normalized with the creatinine levels, correlated with the plasma concentrations. A suitable, convenient and noninvasive method of monitoring patients receiving salbutamol by mechanical ventilation could be implemented. Copyright © 2011 John Wiley & Sons, Ltd.

Variations of the carcinoembryonic antigen level in the plasma of patients with gynecologie cancers during therapy

In 63 patients with histologically proved gynecologie carcinoma, circulating carcinoembryonic antigen (CEA) was determined by radioimmunoassay before and at two intervals after treatment. Thirty-one patients of 63 had CEA values over 2.5 ng. per milliliter before treatment. In general, the CEA levels were low compared to those found in endodermal carcinoma. The percentage of elevated CEA values was slightly higher in cases of carcinoma of the cervix and corpus uteri than in those of carcinoma of the ovary. All patients with CEA levels greater than 2.5 ng. per milliliter treated by complete surgical resection of tumor showed a drop of CEA levels to below 2.5 ng. per milliliter seven weeks after operation. In contrast, patients with palliative therapy showed no change in CEA values. About half of the patients treated with a complete course of internal and external radiotherapy showed a drop of CEA levels to below 2.5 ng. per milliliter, whereas the other patients showed fluctuating CEA values. No correlation between clinical status and evolution of CEA levels in these patients could be drawn at the present time. The CEA test seems to be of little value for the earl of diagnosis of gynecologie carcinoma but appears to be interesting for the evaluation of therapy and the follow-up of patients with diagnosed cases.

Ionizing radiation enhances immunogenicity of cells expressing a tumor-specific T-cell epitope.

BACKGROUND: p53 point mutations represent potential tumor-specific cytolytic T lymphocyte (CTL) epitopes. Whether ionizing radiation (IR) alters the immunological properties of cells expressing mutant p53 in respect of the CTL epitope generated by a defined point mutation has not been evaluated. METHODS: Mutant p53-expressing syngeneic, nontumor forming BALB/c 3T3 fibroblasts, tumor forming ras-transfected BALB/c 3T3 sarcomas, and DBA/2-derived P815 mastocytoma cells, which differ at the level of minor histocompatibility antigens, were used as cellular vaccines. Cells were either injected with or without prior IR into naive BALB/c mice. Cellular cytotoxicity was assessed after secondary restimulation of effector spleen cells in vitro. RESULTS: Injection of P815 mastocytoma cells expressing the mutant p53 induced mutation-specific CTL in BALB/c mice irrespective of prior irradiation. However, syngeneic fibroblasts or fibrosarcomas endogenously expressing mutant p53 were able to induce significant mutation-specific CTL only when irradiated prior to injection into BALB/c mice. IR of fibroblasts did not detectably alter the expression of cell surface molecules involved in immune response induction, nor did it alter the short-term in vitro viability of the fibroblasts. Interestingly, radioactively-labeled fibroblasts injected into mice after irradiation showed altered organ distribution, suggesting that the in vivo fate of these cells may play a crucial role in their immunogenicity. CONCLUSIONS: These findings indicate that IR can alter the immunogenicity of syngeneic normal as well as tumor forming fibroblasts in vivo, and support the view that ionizing radiation enhances immunogenicity of cellular tumor vaccines.

A novel method for quantification of sulfolane (a metabolite of busulfan) in plasma by gas chromatography-tandem mass spectrometry.

The role of busulfan (Bu) metabolites in the adverse events seen during hematopoietic stem cell transplantation and in drug interactions is not explored. Lack of availability of established analytical methods limits our understanding in this area. The present work describes a novel gas chromatography-tandem mass spectrometric assay for the analysis of sulfolane (Su) in plasma of patients receiving high-dose Bu. Su and Bu were extracted from a single 100 μL plasma sample by liquid-liquid extraction. Bu was separately derivatized with 2,3,5,6-tetrafluorothiophenolfluorinated agent. Mass spectrometric detection of the analytes was performed in the selected reaction monitoring mode on a triple quadrupole instrument after electronic impact ionization. Bu and Su were analyzed with separate chromatographic programs, lasting 5 min each. The assay for Su was found to be linear in the concentration range of 20-400 ng/mL. The method has satisfactory sensitivity (lower limit of quantification, 20 ng/mL) and precision (relative standard deviation less than 15 %) for all the concentrations tested with a good trueness (100 ± 5 %). This method was applied to measure Su from pediatric patients with samples collected 4 h after dose 1 (n = 46), before dose 7 (n = 56), and after dose 9 (n = 54) infusions of Bu. Su (mean ± SD) was detectable in plasma of patients 4 h after dose 1, and higher levels were observed after dose 9 (249.9 ± 123.4 ng/mL). This method may be used in clinical studies investigating the role of Su on adverse events and drug interactions associated with Bu therapy.

Determination of trimipramine and its demethylated and hydroxylated metabolites in plasma by gas chromatography-mass spectrometry.

A gas chromatographic-mass spectrometric (GC-MS) method has been developed, for the determination of trimipramine (TRI), desmethyltrimipramine (DTRI), didesmethyltrimipramine (DDTRI), 2-hydroxytrimipramine (2-OH-TRI) and 2-hydroxydesmethyltrimipramine (2-OH-DTRI). The method includes two derivatization steps with trifluoroacetic acid anhydride and N-methyl-N-(tert.-butyldimethyl silyl)trifluoroacetamide and the use of an SE-54 capillary silica column. The limits of quantitation were found to be 2 ng/ml for DTRI and 4 ng/ml for all other substances. Besides, methods have been optimized for the hydrolysis of the glucuronic acid conjugated metabolites. This specific detection method is useful, as polymedication is a usual practice in clinical situations, and its sensitivity allows its use for single-dose pharmacokinetic studies.

Albedo and estimates of net radiation for green beans under polyethylene cover and field conditions

This paper describes the albedo (r) and estimates of net radiation and global solar irradiance for green beans crop (Phaseolus vulgaris L.), cultivated in greenhouse with cover of polyethylene and field conditions, in Botucatu, SP, Brazil (22º 54' S; 48º 27' W; 850 m). The solar global irradiance (Rg) and solar reflected radiation (Rr) were used to estimate the albedo through the ratio between Rr and Rg. The diurnal curves of albedo were obtained for days with clear sky and partially cloudy conditions, for different phenological stages of the crop. The albedo ranged with the solar elevation, the environment and the phenological stages. The cloudiness range have almost no influence on the albedo diurnal amount. The estimation of radiation were made by linear regression, using the global solar irradiance (Rg) and net short-waves radiation (Rc) as independent variables. All estimates of radiation showed better adjustment for specific phenological periods compared to the entire crop growing cycle. The net radiation in the greenhouse has been estimated by the global solar irradiance measured at field conditions.

Radiation and energy balance of lettuce culture inside a polyethylene greenhouse

The objective of this paper was to describe the radiation and energy balance, during the lettuce (Lactuca sativa, L. cv. Verônica) crop cycle inside a polyethylene greenhouse. The radiation and energy balance was made inside a tunnel greenhouse with polyethylene cover (100 mum) and in an external area, both areas with 35 m². Global, reflected and net radiation, soil heat flux and air temperature (dry and humid) were measured during the crop cycle. A Datalogger, which operated at 1 Hz frequency, storing 5 minutes averages was utilized. The global (K¯) and reflected (K­) radiations showed that the average transmission of global radiation (K¯in / K¯ex) was almost constant, near to 79.59%, while the average ratio of reflected radiation (K­in / K­ex) was 69.21% with 8.47% standard-deviation. The normalized curves of short-wave net radiation, in relation to the global radiation (K*/ K¯), found for both environments, were almost constant at the beginning of cycle; this relation decreased in the final stage of culture. The normalized relation (Rn/ K¯) was bigger in the external area, about 12%, when the green culture covered the soil surface. The long-wave radiation balance average (L*) was bigger outside, about 50%. The energy balance, estimated in terms of vertical fluxes, showed that, for the external area, in average, 83.07% of total net radiation was converted in latent heat evaporation (LE), and 18% in soil heat flux (G), and 9.96% in sensible heat (H), while inside of the greenhouse, 58.71% of total net radiation was converted in LE, 42.68% in H, and 28.79% in G.