179 research outputs found
Optimized determination of clobazam in human plasma with extraction and high-performance liquid chromatography analysis
No full textNMR spectrocopic analysis of rat brain development:in vitro proton and carbon studies of whole tissue and its phospholipid fraction
No full textThe developmental patterns of the rat brain at several postnatal time points were investigated in Folch (chloroform-methanol) extracts. The chloroform- (lipid-containing) and water-soluble (cytosolic) fractions of whole-tissue extracts and the phospholipid fraction separated from the organic fraction by chromatography were analysed by means of high-resolution1H and 13C nuclear magnetic resonance (NMR) spectroscopy. Analysis of the cytosolic fraction showed the changing patterns of several brain metabolites during postnatal maturation, in full agreement with data obtained from perchloric acid extracts. 1H NMR spectroscopy of the phospholipid fraction allowed for quantitative evaluation of fatty acid acyl chain length, mean unsaturation and mean polyunsaturation. It was found that both mean unsaturation and polyunsaturation are lower in adult brain phospholipids than during the first 3 postnatal weeks. 13C NMR spectroscopy of the same fraction showed that the molar percentage of C18 fatty acids (oleic, linoleic, linolenic) in brain phospholipids is similar at all the investigated time points. These results indicate that the combination of Folch extraction with simple chromatographic procedures and NMR analysis yields useful data to define the chemical maturation of the brain. Copyright © 2001 S. Karger AG, Basel
Impact of Residual Setup Error on Parotid Gland Dose in Intensity-Modulated Radiation Therapy with or without Planning Organ-at-Risk Margin
No full textPurpose: To estimate the dosimetric impact of residual setup errors on parotid sparing in head-and-neck (H&N) intensity-modutated treatments and to evaluate the effect of employing an PRV (planning organ-at-risk volume) margin for the parotid gland. Patients and Methods: Ten patients treated for H&N cancer were considered. A nine-beam intensity-modutated radiotherapy (IMRT) was planned for each patient. A second optimization was performed prescribing dose constraint to the PRV of the parotid gland. Systematic setup errors of 2 mm, 3 mm, and 5 mm were simulated. The dose-volume histograms of the shifted and reference plans were compared with regard to mean parotid gland dose (MPD), normal-tissue complication probability (NTCP), and coverage of the clinical target volume (V(95%) and equivalent uniform dose [EUD]); the sensitivity of parotid sparing on setup error was evaluated with a probability-based approach. Results: MPD increased by 3.4%/mm and 3.0%/mm for displacements in the craniocaudal and lateral direction and by 0.7%/mm for displacements in the anterior-posterior direction. The probability to irradiate the parotid with a mean dose > 30 Gy was > 50%, for setup errors in cranial and lateral direction and < 10% in the anterior-posterior direction. The addition of a PRV margin improved parotid sparing, with a relative reduction in NTCP of 14%. The PRV margin compensates for setup errors of 3 mm and 5 mm (MPD <= 30 Gy in 87% and 60% of cases), without affecting clinical target volume coverage (V(95%) and EUD variations < 1% and < 1 Gy). Conclusion: The parotid gland is more sensitive to craniocaudal and lateral displacements. A setup error of 2 mm guarantees an MPD : 30 Gy in most cases, without adding a PRV margin. If greater displacements are expected/accepted, an adequate PRV margin could be used to meet the clinical parotid gland constraint of 30 Gy, without affecting target volume coverage
HPLC analysis of HbA1c in dried blood spot samples (DBS): a reliable future for diabetes monitoring
No full textTo simplify collection and transport of blood for HbA1c measuring, we have studied the use of a special paper that absorbs a defined volume of capillary blood and quickly dries it (dried blood-spot, DBS). The DBS can be sent to a central laboratory using regular postal service and without temperature control. This system differs greatly from other proposed DBS methods for HbA1c because it overcomes the haemoglobin alterations during the drying and storing processes, that otherwise make this analysis unreliable. We have developed a special treatment of the paper before collection that stabilises the HbA1c molecule excellently in dried blood samples, allowing accurate HPLC analysis even two weeks after collection. This method has been applied in a "blind" study in which HbA1c values determined in 97 DBS coming from an hospital diabetes care centre were compared with those obtained from parallel venous blood samples
Cisplatin, hyperthermia, and radiation (trimodal therapy) in patients with locally advanced head and neck tumors: A phase I-II study
No full textPurpose: Hyperthermia is now being widely used to treat clinical malignancies especially combined with radiotherapy and more rarely with chemotherapy. The combination of heat, radiation, and chemotherapy (trimodality) can lead to potent interaction. The present Phase I-II study was conducted to evaluate the feasibility and acute toxicity of a combination of cisplatin, hyperthermia, and irradiation in the treatment of superficial cervical nodal metastases from head and neck cancer. Methods and Materials: Eighteen patients with measurable neck metastases from previously untreated squamous cell head and neck tumors were entered into the trial. Therapy consisted of a conventional irradiation (total dose 70 Gy, 2 Gy five times a week) combined with a weekly administration of 20 mg/m2 iv of cisplatin and a total of two sessions of local external microwave hyperthermia (desired temperature of 42.5°C for 30 min). Results: Feasibility of the treatment was demonstrated. Acute local toxicity was mild; no thermal blisters or ulcerations were reported and only two patients experienced local pain during hyperthermia. Cutaneous toxicity appeared greater than in our previous studies with irradiation plus hyperthermia and irradiation plus cisplatin. Systemic toxicity was moderate with major toxic effects observed in three patients (World Health Organization (WHO) grade 3 anaemia). Even though it was not an aim of the study to evaluate the nodal response, we observed a complete response rate of 72.2% (95% confidence interval 51-93.4%), 16.6% of partial response and 11.1% of no change. Conclusion: The study confirms the feasibility of the combination of cisplatin, heat, and radiation with an acceptable toxicity profile. The trimodal therapy deserves further evaluation as a way to enhance the efficacy of irradiation in the treatment of nodal metastases from head and neck tumors
Population genomics from a food matrix: estimating csd variability using next generation sequencing on Apis mellifera DNA present in honey
No full textThe complementary sex determiner (csd) gene is a crucial genetic factor in the sex determination of Apis mellifera L. Females only develop if fertilized eggs have functional heterozygous genotypes at this gene. Males, being haploids, are emizygous. Two identical csd alleles result in non-viable males. Given the recent decline in honey bee populations, it is imperative to monitor allele variability at this gene to prevent negative effects of high inbreeding levels. In this study, we evaluated the use of next generation sequencing in conjunction with environmental honey DNA as a source of honey bee genomic information to obtain extensive sequencing data for analysing variability at the hypervariable region (HVR) of the csd gene. DNA was extracted from several honey samples directly collected from oneycombs of various colonies. A bioinformatic pipeline was utilised to analyse approx. 1.5 million reads, identifying a total of 160 different csd alleles, 55% of which were novel. The average number of alleles per sample corresponded with the expected number of patrilines per colony, based on queen mating behaviour. The diversity of alleles at the csd gene could also offer valuable information for reconstructing the honey bee population genetic history
Hyperfractionated radiation in combination with local hyperthermia in the treatment of advanced squamous cell carcinoma of the head and neck : A phase I-II study
No full textTwenty-seven patients with cervical metastases from squamous cell head and neck tumours were treated with hyperfractionated XRT (total dose 69.60- 76.80 Gy, 1.2 Gy b.i.d. five times a week) combined with a total of two to six sessions of superficial external HT. Acute local toxicity WaS mild; as major acute side effects, only one ulceration was recorded. No severe late side effects were observed. Late toxicity was similar to that observed in our previous studies with the combination of heat and radiation. Nodal complete response was observed in 77% of patients, partial response was observed in 15% of patients and no change was observed in 8% of patients. Five-year actuarial nodal control was 64.5 ± 19% and 5-year actuarial survival was 24 ± 10%. The treatment of nodal metastases from head and neck turnouts with the combination of HT and hyperfractionated XRT is feasible with an acceptable acute and late toxicity profile
A comprehensive atlas of nuclear sequences of mitochondrial origin (NUMT) inserted into the pig genome
No full textBackground: The integration of nuclear mitochondrial DNA (mtDNA) into the mammalian genomes is an ongoing, yet rare evolutionary process that produces nuclear sequences of mitochondrial origin (NUMT). In this study, we identified and analysed NUMT inserted into the pig (Sus scrofa) genome and in the genomes of a few other Suinae species. First, we constructed a comparative distribution map of NUMT in the Sscrofa11.1 reference genome and in 22 other assembled S. scrofa genomes (from Asian and European pig breeds and populations), as well as the assembled genomes of the Visayan warty pig (Sus cebifrons) and warthog (Phacochoerus africanus). We then analysed a total of 485 whole genome sequencing datasets, from different breeds, populations, or Sus species, to discover polymorphic NUMT (inserted/deleted in the pig genome). The insertion age was inferred based on the presence or absence of orthologous NUMT in the genomes of different species, taking into account their evolutionary divergence. Additionally, the age of the NUMT was calculated based on sequence degradation compared to the authentic mtDNA sequence. We also validated a selected set of representative NUMT via PCR amplification. Results: We have constructed an atlas of 418 NUMT regions, 70 of which were not present in any assembled genomes. We identified ancient NUMT regions (older than 55 million years ago, Mya) and NUMT that appeared at different time points along the Suinae evolutionary lineage. We identified very recent polymorphic NUMT (private to S. scrofa, with < 1 Mya), and more ancient polymorphic NUMT (3.5–10 Mya) present in various Sus species. These latest polymorphic NUMT regions, which segregate in European and Asian pig breeds and populations, are likely the results of interspecies admixture within the Sus genus. Conclusions: This study provided a first comprehensive analysis of NUMT present in the Sus scrofa genome, comparing them to NUMT found in other species within the order Cetartiodactyla. The NUMT-based evolutionary window that we reconstructed from NUMT integration ages could be useful to better understand the micro-evolutionary events that shaped the modern pig genome and enriched the genetic diversity of this species
Il dosaggio dell’hba1c su blood spot negli studi di popolazione e nell’automonitoraggio del diabete
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