Evaluation of superficially and fully porous particles for HILIC separation of lanthanide-polyaminocarboxylic species and simultaneous coupling to ESIMS and ICPMS.

In this work, amide-bonded columns packed with fully porous particles (FPP) and superficially porous particles (SPP) were evaluated to separate lanthanide-polyaminocarboxylic species by hydrophilic interaction liquid chromatography (HILIC), using two model samples of interest in nuclear and other industrial applications. We assessed the gains achieved by reducing the dimensions of the columns along with the size of the FPPs to sub-2 µm and by using sub-3 µm SPP-packed columns. The FPP-packed Acquity column (100 × 2.1 mm; 1.7 µm) performed better than the SPP-packed Accucore column (150 × 2.1 mm; 2.6 µm), with a separation that was two times more efficient and three times shorter, while generating around 30% less in effluent volumes. This column was also coupled simultaneously to electrospray ionisation mass spectrometry (ESIMS) and inductively coupled plasma mass spectrometry (ICPMS). The instrumental set-up was performed in a conventional laboratory, by taking into account the geometrical constraints existing in the laboratory dedicated to radioelement analysis. Furthermore, separation of the series of lanthanide (Ln) species was demonstrated for the first time thanks to the separation mode of hydrophilic interaction liquid chromatography.

Challenges in initiating and conducting personalized cancer therapy trials: perspectives from WINTHER, a Worldwide Innovative Network (WIN) Consortium trial.

Advances in 'omics' technology and targeted therapeutic molecules are together driving the incorporation of molecular-based diagnostics into the care of patients with cancer. There is an urgent need to assess the efficacy of therapy determined by molecular matching of patients with particular targeted therapies. WINTHER is a clinical trial that uses cutting edge genomic and transcriptomic assays to guide treatment decisions. Through the lens of this ambitious multinational trial (five countries, six sites) coordinated by the Worldwide Innovative Networking Consortium for personalized cancer therapy, we discovered key challenges in initiation and conduct of a prospective, omically driven study. To date, the time from study concept to activation has varied between 19 months at Gustave Roussy Cancer Campus in France to 30 months at the Segal Cancer Center, McGill University (Canada). It took 3+ years to be able to activate US sites due to national regulatory hurdles. Access to medications proposed by the molecular analysis remains a major challenge, since their availability through active clinical trials is highly variable over time within sites and across the network. Rules regarding the off-label use of drugs, or drugs not yet approved at all in some countries, pose a further challenge, and many biopharmaceutical companies lack a simple internal mechanism to supply the drugs even if they wish to do so. These various obstacles should be addressed to test and then implement precision medicine in cancer.

Cobalt toxicity: chemical and radiological combined effects on HaCaT keratinocyte cell line.

Cobalt (Co) is an essential trace element well known as a constituent of vitamin B(12), but different compounds of Co are also described as highly toxic and/or radiotoxic for individuals or the environment. In nuclear power plants, (58)Co and (60)Co are radioactive isotopes of cobalt present as activation products of stable Co and Ni used in alloys. Skin exposure is a current occupational risk in the hard metal and nuclear industries. As biochemical and molecular cobalt-induced toxicological mechanisms are not fully identified, we investigated cobalt toxicity in a model human keratinocyte cell line, HaCaT. In this study, we propose a model to determine the in vitro chemical impact on cell viability of a soluble form of cobalt (CoCl(2)) with or without gamma-ray doses to mimic contamination by (60)Co, to elucidate the mechanisms of cobalt intracellular chemical and radiological toxicity. Intracellular cobalt concentration was determined after HaCaT cell contamination and chemical toxicity was evaluated in terms of cellular viability and clonogenic survival. We investigated damage to DNA in HaCaT cells by combined treatment with chemical cobalt and a moderate gamma-ray dose. Additive effects of cobalt and irradiation were demonstrated. The underlying mechanism of cobalt toxicity is not clearly established, but our results seem to indicate that the toxicity of Co(II) and of irradiation arises from production of reactive oxygen species.

Spontaneous oesophageal perforation.

An autopsy was performed on a young adult, who apparently died during his sleep. Mediastinitis was established and empyema was also found in left pleural cavity. The oesophagus examination showed a tear in left side. The lesion occurred in the distal oesophagus and showed the leak communicating freely with the left pleural space. Oesophageal perforation was the source of empyema, resulted from barotrauma to the lower oesophagus during the effort of vomiting. Death caused by septic shock. Boerhaave syndrome is a serious and rapidly fatal spontaneous oesophagus rupture. Forceful ejection of gastric contents in an unrelaxed oesophagus against a closed glottis is the mechanism described. The tear thus produced is vertical. The case report discusses the historical, statistical, pathophysiological, diagnostic and therapeutic aspects of Boerhaave syndrome. The syndrome is a cause of sudden death, which be known by forensic pathologists.

Cerebellar-pulmonary embolism, cause of death in the newborn.

A 28-year-old woman delivered twin girls. The first twin was delivered without any difficulty. The head of the second twin failed to descend with pushing. A special kind of obstetrical forceps, Thierry's spatulas, were used to extract the second twin in the occipito-posterior vertex position. She was declared dead after recording Apgar scores of 0 and 0 and after 35 min of resuscitation. An autopsy was performed for medico-legal reasons. Macroscopic examination of the brain showed a small area of leptomeningeal haemorrhage in the left sylvian fossa and the base of the brain. Histopathological studies demonstrated cerebellar tissue emboli in meningeal and pulmonary arteries. Excessive pressure on the suboccipital region during delivery can cause traumatic separation of the occipital chondral junctions, which may lead to separation of the occipital squama from lateral parts of the occipital bones. The inferior part of the occipital squama is displaced forward and upward into the posterior fossa. This produces tearing of the duramater and occipital sinuses leading to leptomeningeal haemorrhage in the posterior cranial fossa, often associated with cerebellar lesions. Major stretching and tearing of the posterior aspect of tentorium cerebelli in contact with the sinuses and the cerebellar cortex may also occur, inducing slight movement of the occipital bones and subsequent emboli. This case study is that of a newborn death due to pulmonary cerebellar tissue embolism occurring during delivery with Thierry's forceps, which are considered less traumatic to the foetal cranium. A review of the literature identified 17 other published cases. In difficult deliveries this pathology should sought carefully. Brain, lung and placenta tissue sections must be studied.

An interdisciplinary approach to investigate the impact of cobalt in a human keratinocyte cell line.

Since in nuclear power plants, risks of skin contact contamination by radiocobalt are significant, we focused on the impact of cobalt on a human cutaneous cell line, i.e. HaCaT keratinocytes. The present paper reports an interdisciplinary approach aimed at clarifying the biochemical mechanisms of metabolism and toxicity of cobalt in HaCaT cells. Firstly, a brief overview of the used instrumental techniques is reported. The following parts present description and discussion of results concerning: (i) toxicological studies concerning cobalt impact towards HaCaT cells (ii) structural and speciation fundamental studies of cobalt-bioligand systems, through X-ray absorption spectroscopy (XAS), ab initio and thermodynamic modelling (iii) preliminary results regarding intracellular cobalt speciation in HaCaT cells using size exclusion chromatography/inductively coupled plasma-atomic emission spectroscopy (SEC/ICP-AES) and direct in situ analysis by ion beam micropobe analytical techniques.

Triethoxysilyl-substituted aminoethanethiol ligands for zinc and cadmium complexes and aminoethanethiol-modified silica gel. Evaluation of the corresponding supported molecular trap for metallic pollutant uptake (Cd2+, Hg2+ and Pb2+).

The reaction of 2-[3-(triethoxysilyl)propylamino]ethanethiol (LH, a) and 1-methyl-2-[3-(triethoxysilyl)propylamino]ethanethiol (LH, b) with ZnX2 and CdX2 (X = Cl, Br, I, NO3) in tetrahydrofuran (THF) or CH2Cl2 gives several complexes depending on the experimental conditions. Elemental analyses, IR, Raman, 13C[1H], 1H NMR and mass spectroscopies indicated the formation of mononuclear and dinuclear complexes. In the absence of NEt3 as proton quencher, the protonated ligands react in their zwitterionic form giving dinuclear [M(LH)X2]2 [M = Zn (1), Cd (2); LH = a, b; X = Cl, Br, I] or mononuclear M(NO3)2(LH)2 [M = Zn (5), Cd (6); LH = a] complexes. In both cases, coordination occurs through the S atoms, the ligands acting as terminal and bridging species. With NEt3, the deprotonated ligands are chelated through their N and S atoms and bridging occurs through the S atoms in [MLX]2 [M = Zn (3), Cd (4); LH = a; X = Cl, Br] complexes. The LH ligand is chemically grafted onto silica, the procedure optimized and the resulting material characterized by 13C and 29Si cross-polarization, magic-angle spinning (CP-MAS) NMR and DRIFT. This material is evaluated as a supported molecular trap for binding heavy metals (Cd2+, Hg2+, Pb2+) in aqueous solution. In both batch and column processes, it appears that Hg2+ and Pb2+ are trapped more than Cd2+, but in all cases values lower than those allowed were obtained.

Improved vessel visualization in MR angiography by nonlinear anisotropic filtering.

This paper deals with a preprocessing technique of magnetic resonance angiography (MRA) images, applied before maximum-intensity-projection (MIP). The purpose was to recover small low-intensity vessels, visible in individual slices, but lost in MIP images that usually have higher background level than the individual slices. The authors have developed a nonlinear three-dimensional spatial filtering technique (called HD filter) based on anisotropic smoothing. The filter first searches for the local orientation of the vessel. It then performs a nonlinear smoothing in the vessel's local direction so as to avoid blurring its boundaries. Noise level reduction, contrast enhancement, and improved small vessel visibility achieved by this filter are illustrated on dynamic contrast-enhanced subtraction MRA images of the lower limbs.

No trend toward a spontaneous improvement of hyperparathyroidism and high bone turnover in normocalcemic long-term renal transplant recipients.

Although hyperparathyroidism is a common feature in renal transplant recipients, the long-term course of parathyroid hormone (PTH) secretion in these patients is not well established, and the actual contribution of PTH to posttransplant bone disease remains incompletely understood. Therefore, we studied calcium-regulating hormones and serum osteocalcin, as a marker of bone remodeling, in 82 normocalcemic renal transplant recipients with good renal function who had received a graft 6 to 73 months previously and in 82 healthy subjects matched for age and sex. In all subjects, fasting serum and 24-hour urinary samples were collected. The transplant recipients had excessive PTH secretion (serum PTH, 6.9 +/- 0.5 pmol/L in recipients v 3.0 +/- 0.1 pmol/L in healthy subjects; P < 0.001) and high bone turnover (osteocalcin, 16.6 +/- 0.8 microg/L v 8.0 +/- 0.3 microg/L; P < 0.001). (Values are mean +/- SEM.) In addition, transplant recipients had a slightly higher ionized calcium than the healthy subjects, providing definite evidence of an inappropriate PTH secretion in renal transplant recipients. Furthermore, in subgroups of 25 recipients and 25 healthy controls matched for creatinine clearance, the results superimposed those obtained in the whole groups, suggesting that excessive PTH secretion and high bone turnover in renal transplant recipients did not merely reflect the moderately reduced renal function of some recipients. In the whole group of transplant recipients, PTH correlated positively with osteocalcin (r = 0.40; P < 0.001), suggesting that PTH contributes at least partly to posttransplant bone disease. Conversely, there was no correlation between serum PTH or osteocalcin and the delay from grafting. Therefore, our results provide no evidence for a spontaneous improvement of either persistent hyperparathyroidism or high bone turnover in normocalcemic long-term renal transplant recipients.