Separation of free amino acids in human plasma by capillary electrophoresis with laser induced fluorescence: potential for emergency diagnosis of inborn errors of metabolism.

Free amino acids (AAs) in human plasma are derivatized with 3-(4-carboxybenzoyl)quinoline-2-carboxaldehyde (CBQCA) and analyzed by capillary electrophoresis (CE) with laser induced fluorescence (LIF) detection. The labeling procedure is significantly improved over results reported previously. Derivatization can be completed in 40 min, with concentrations as low as 4 x 10(-8) M successfully labeled in favourable cases. Twenty-nine AAs (including 2 internal standards) are identified and can be reproducibly separated in 70 min. Migration time RSD values for 23 of these AAs were calculated and found in the range from 0.5 to 4%. The rapid derivatization procedure and the resolution obtained in the separation are sufficient for a semi-quantitative, emergency diagnosis of several inborn errors of metabolism (IEM). Amino acid profiles for both normal donor plasma samples and plasma samples of patients suffering from phenylketonuria, tyrosinemia, maple syrup urinary disease, hyperornithinemia, and citrullinemia are studied.

Reforms of the pre-graduate curriculum for medical students: the Bologna process and beyond.

For several years, all five medical faculties of Switzerland have embarked on a reform of their training curricula for two reasons: first, according to a new federal act issued in 2006 by the administration of the confederation, faculties needed to meet international standards in terms of content and pedagogic approaches; second, all Swiss universities and thus all medical faculties had to adapt the structure of their curriculum to the frame and principles which govern the Bologna process. This process is the result of the Bologna Declaration of June 1999 which proposes and requires a series of reforms to make European Higher Education more compatible and comparable, more competitive and more attractive for Europeans students. The present paper reviews some of the results achieved in the field, focusing on several issues such as the shortage of physicians and primary care practitioners, the importance of public health, community medicine and medical humanities, and the implementation of new training approaches including e-learning and simulation. In the future, faculties should work on several specific challenges such as: students' mobility, the improvement of students' autonomy and critical thinking as well as their generic and specific skills and finally a reflection on how to improve the attractiveness of the academic career, for physicians of both sexes.

Metallic renal artery MR imaging stent: artifact-free lumen visualization with projection and standard renal MR angiography.

A cardiac-triggered free-breathing three-dimensional (3D) balanced fast field-echo projection renal magnetic resonance (MR) angiographic sequence was investigated for in-stent lumen visualization of a dedicated metallic renal artery stent. Fourteen prototype stents were deployed in the renal arteries of six pigs (in two pigs, three stents were deployed). Projection renal MR angiography was compared with standard contrast material-enhanced 3D breath-hold MR angiography. Artifact-free in-stent lumen visualization was achieved with both projection MR angiography and contrast-enhanced MR angiography. These promising results warrant further studies for visualization of in-stent restenosis.

Cognition, Resources, and Institutions in the Explanation of Attitudes to Free Trade

This article proposes a framework for the analysis of attitudes to foreign trade policies that challenges the traditional skill-endowment approach. The traditional approach assumes informed individuals who calculate the costs and benefits of alternative policies. We propose that individuals lack information and that their positions rest on economic vulnerability, as mediated through risk-aversion. We also stress the role of environmental signals and political endorsements in guiding individuals' views on trade policy. We test this alternative approach with a Spanish survey conducted in May 2009 and the ISSP survey conducted in 2003 in a large number of less developed and more developed countries. The Spanish data show that the population is largely uninformed and that their ideas about the consequences of free trade policy do not explain attitudes among different socio-demographic groups. Meanwhile, the ISSP data contradict important aspects of the traditional approach and are consistent with the alternative approach.

Die Inguinal-Hernienplastik nach Lichtenstein: Eine einfache und komplikationsarme Technik, besonders geeignet für die Tageschirurgie [The Lichtenstein inguinal hernia-plasty: a simple and complication-free technique, especially suited for ambulatory surgery].

A consecutive series of 353 patients who underwent Lichtenstein mesh repair for inguinal hernia from the 1st of July 1994 to the 30th of July 1995 were studied. We analysed our indication, technique, complications, follow-up and outcome. Special consideration was given to the advantages and acceptance of day-case surgery. Our results suggest that the Lichtenstein repair should be considered as a new standard procedure, especially outside of hernia centres.

Sulphate-reducing bacteria associated with biocorrosion: a review

Biocorrosion means any process of corrosion in wich microorganisms are somehow involved. As far as the petroleum industry is concerned, the anaerobic type is the more important, with Sulphate-Reducing Bacteria (SRB) accouting for half of the described processes. SRB are obligate anaerobs that use sulphur, sulphate or other oxidized sulphur compounds as oxidizing agents when decomposing organic material. A typical product of SRB metabolism, hydrogen sulphide -H2S-, is extremely toxic. In the present work we review the literature on mechanisms underlying biocorrosive process in wich SRB are involved and summarize some of the ultrastructural and eletrochemical work developed using SRB obtained from water injection flow in wells located on PETROBRAS offshore marine plataforms, sampled directly in the field over metallic probes, or cultured under laboratory conditions. Biofilms develop when SRB adhere to inert surfaces. A high diversity of morphological types is found inside these biofilms. Their extracellular matrix is highly hydrated and mainly anionic, as shown by its avid reaction with cationic compounds like ruthenium red. We have noted that variations in iron contet lead to interesting changes in the ultrastructure of the bacterial cell coat and also in the rate of corrosion induced in metallic test cupons. Since routine methods to prevent and treat SRB contamination and biodeterioration involve the use of biocides that are toxic and always have some environmental impact, an accurate diagnosis of biocorrosion is always required prior to a treatment decision. We developed a method that detects and semi-quantifies the presence of living or dead SRB by using free silver potentials as an indicator of corrosive action by SRB-associated sulphides. We found a correlation between sulphide levels (determined either by spectrophotometry, or using a silver electrode -E(Ag)- that measured changes in free potentials induced by the presence of exogeneously added sulphide) and SRB concentration (enumerated by a culturing method). E (Ag) was characterized under a variety of conditions andwas found to be relatively immune to possible interference resulting from aeration of media or from the psence of iron corrosion products. The method offers a simple, rapid, and effective means of diagnosing biocorrosive processes prior to their control.

Plasma Level of Mmp-9 as Predictive Factor for Response and Progression Free Survival in Patients Treated with Bevacizumab (Bev) and Pegylated Liposomal Doxorubicin (Pld): Sakk 24/06

Background: There is currently no identified marker predicting benefit from Bev in patients with breast cancer (pts). We monitored prospectively 6 angiogenesis-related factors in the blood of advanced stage pts treated with a combination of Bev and PLD in a phase II trial of the Swiss Group for Clinical Cancer Research, SAKK.Methods: Pts received PLD (20 mg/m2) and Bev (10 mg/kg) every 2 weeks for a maximum of 12 administrations, followed by Bev monotherapy until progression or severe toxicity. Blood samples were collected at baseline, during treatment and at treatment discontinuation. Enzyme-linked immunosorbent assays (Quantikine, R&DSystems and Reliatech) were used to measure vascular endothelial growth factor (VEGF), placental growth factor (PlGF), matrix metalloproteinase 9 (MMP-9) and soluble VEGF receptors -1, -2 and -3. The natural log-transformed (ln) data for each factor was analyzed by analysis of variance (ANOVA) model to investigate differences between the mean values of the subgroups of interest (where a = 0.05), based on the best tumor response by RECIST.Results: 132 samples were collected in 41 pts. The mean of baseline ln MMP-9 levels was significantly lower in pts with tumor progression than those with tumor response (p=0.0202, log fold change=0.8786) or disease control (p=0.0035, log fold change=0.8427). Higher MMP-9 level was a significant predictor of superior progression free survival (PFS): p=0.0417, hazard ratio=0.574, 95% CI=0.336-0.979. In a multivariate cox proportional hazards model, containing performance status, disease free interval, number of tumor sites, visceral involvement and prior adjuvant chemotherapy, using stepwise regression baseline MMP-9 was still a statistically 117P Table 1. SOLTI-0701* AC01B07* NU07B1* SOR+CAP N=20 PL+CAP N=33 SOR+ GEM/CAP N=23 PL+ GEM/CAP N=27 SOR+PAC N=48 PL+PAC N=46 Baseline characteristics Age, median (range), y 49 (32-72) 53 (30-78 54 (32-69) 57 (31-82) 50 (27-80) 52 (23-74) AJCC stage, n (%) IIIB/IIIC 3 (15) 6 (18) 0 (0) 3 (11) 8 (17) 9 (20) IV 17 (85) 27 (82) 23 (100) 24 (89) 40 (83) 37 (80) Metastatic site, n (%) Non-visceral 3 (15) 6 (18) 7 (30) 6 (22) 9 (19) 17 (37) Visceral 17 (85) 27 (82) 16 (70) 21 (78) 39 (81) 29 (63) Prior metastatic chemo, n (%) 8 (40) 15 (45) 21 (91) 25 (93) - - Efficacy PFS, median, mo 4.3 2.5 3.1 2.6 5.6 5.5 HR (95% CI)_ 0.60 (0.31, 1.14) 0.57 (0.30, 1.09) 0.86 (0.50, 1.45) 1-sided P value_ 0.055 0.044 0.281 Overall survival, median, mo 17.5 16.1 Pending 14.7 18.2 HR (95% CI)_ 0.98 (0.50, 1.89) 1.11 (0.64, 1.94) 1-sided P value_ 0.476 0.352 Safety N=20 N=33 N=22 N=27 N=46 N=46 Tx-emergent Grade 3/4, n (%) 15 (75) 16 (48) 20 (91) 17 (63) 36 (78) 16 (35) Grade 3§ hand-foot skin reaction/ syndrome 8 (40) 5 (15) 8 (36) 0 (0) 14 (30) 2 (4) *Efficacy results based on intent-to-treat population and safety results based on safety population (pts who received study drug[s]); _Cox regression within each subgroup; _log-rank test within each subgroup; §maximum toxicity grade for hand-foot skin reaction/syndrome; AJCC, American Joint Committee on Cancer mittedabstractsª The Author 2011. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com Downloaded from annonc.oxfordjournals.org at Bibliotheque Cantonale et Universitaire on June 6, 2011 significant factor (p=0.0266). The results of the other measured factors were presented elsewhere.Conclusions: Higher levels of MMP-9 could predict tumor response and superior PFSin pts treated with a combination of Bev and PLD. These exploratory results justify further investigations of MMP-9 in pts treated with Bev combinations in order to assess its role as a prognostic and predictive factor.Disclosure: K. Zaman: Participation in advisory board of Roche; partial sponsoring ofthe study by Roche (the main sponsor was the Swiss Federation against Cancer (Oncosuisse)). B. Thu¨rlimann: stock of Roche; Research grants from Roche. R. vonMoos: Participant of Advisory Board and Speaker honoraria

Use of glass beads and CF 11 cellulose for removal of leukocytes from malaria-infected human blood in field settings

Passage of malaria infected blood through a two-layered column composed of acid-washed glass beads and CF 11 cellulose removes white cells from parasitized blood. However, because use of glass beads and CF 11 cellulose requires filtration of infected blood separately through these two resins and the addition of ADP, the procedure is time-consuming and may be inapropriate for use in the field, especially when large numbers of blood samples are to be treated. Our modification of this process yields parasitized cells free of contaminating leukocytes, and because of its operational simplicity, large numbers of blood samples can be processed. Our procedure also compares well with those using expensive commercial Sepacell resins in its ability to separate leukocytes from whole blood. As a test of usefulness in molecular biologic investigations, the parasites obtained from the blood of malaria-infected patients using the modified procedure yield genomic DNA whose single copy gene, the circumsporozite gene, efficiently amplifies by polymerase chain reaction.

Clinicopathologic correlates in the oldest-old: Commentary on "No disease in the brain of a 115-year-old woman".

den Dunnen et al. [den Dunnen, W.F.A., Brouwer, W.H., Bijlard, E., Kamphuis, J., van Linschoten, K., Eggens-Meijer, E., Holstege, G., 2008. No disease in the brain of a 115-year-old woman. Neurobiol. Aging] had the opportunity to follow up the cognitive functioning of one of the world's oldest woman during the last 3 years of her life. They performed two neuropsychological evaluations at age 112 and 115 that revealed a striking preservation of immediate recall abilities and orientation. In contrast, working memory, retrieval from semantic memory and mental arithmetic performances declined after age 112. Overall, only a one-point decrease of MMSE score occurred (from 27 to 26) reflecting the remarkable preservation of cognitive abilities. The neuropathological assessment showed few neurofibrillary tangles (NFT) in the hippocampal formation compatible with Braak staging II, absence of amyloid deposits and other types of neurodegenerative lesions as well as preservation of neuron numbers in locus coeruleus. This finding was related to a striking paucity of Alzheimer disease (AD)-related lesions in the hippocampal formation. The present report parallels the early descriptions of rare "supernormal" centenarians supporting the dissociation between brain aging and AD processes. In conjunction with recent stereological analyses in cases aged from 90 to 102 years, it also points to the marked resistance of the hippocampal formation to the degenerative process in this age group and possible dissociation between the occurrence of slight cognitive deficits and development of AD-related pathologic changes in neocortical areas. This work is discussed in the context of current efforts to identify the biological and genetic parameters of human longevity.

Gamma Knife radiosurgery after previous microvascular decompression decreases the chances of pain free in classical trigeminal neuralgia

Purpose: To evaluate the safety-efficacy of Gamma Knife surgery (GKS) as a second treatment for classical trigeminal neuralgia (CTN), and the influence of prior microvascular decompression (MVD). Methods: Between July 1992 and November 2010, 737 patients have been operated with GKRS for ITN and prospectively evaluated in Timone University Hospital in Marseille, France. Among these, 54 patients had a previous history of MVD. Radiosurgery using a Gamma Knife (model B or C or Perfexion) was performed on the basis of on both MR and CT targeting. A single 4 mm isocenter was positioned in the cisternal portion of the trigeminal nerve at a median distance of 7.6 mm (range 3.9-11.9) anteriorly to the emergence of the nerve (retrogasserian target). A median maximum dose of 85 Gy (range 70-90) was delivered. Here, the 45 patients with previous MVD and a follow-up longer than one year are evaluated (the patients with megadolichobasilar artery compression and multiple sclerosis were excluded). Results: The median age in this series was 56.75 years (range 28.09-82.39). The median follow-up period was 39.48 months (range 14.10-144.65). All the patients had a past history of surgery, with at least one previous failed MVD, but also radiofrequency lesion (RFL) in 16 patients (35.6%), balloon microcompression in 7 (15.6%) and glycerol rhizotomy in 1 (2.2%). Thirty-five patients (77.8%) were initially pain free after GKS within a median time of 14 days (range 0, 180). Patients from this group had less probability of being pain free compared to our global population of essential trigeminal neuralgia without previous MVD history (p=0.010, hazard ratio of 0.64). Their probability of remaining pain free at 3, 5, 7 and 10 years was 66.5%, 59.1%, 59.1% and 44.3%, respectively. Twelve patients (34.3%) initially pain free experienced a recurrence with a median delay of 31.21 months (range 3.40-89.93). The hypoesthesia actuarial rate at 1 year was 9.1% and remained stable till 12 years with a median delay of onset of 8 months (range 8-8). Conclusions: Retrogasserian GKS proofed to be safe and effective on the long-term basis even after failed previous MVD. Even if the initial result of pain free was only 77.8%, the toxicity was low with only 9.1% hypoesthesia. No patient reported a bothersome hypoesthesia. The probability of maintaining pain relief in the long-term was of 44.3% at 10 years.

Macrophages induce neutrophil apoptosis through membrane TNF, a process amplified by Leishmania major.

Neutrophils are recruited to the site of parasite inoculation within a few hours of infection with the protozoan parasite Leishmania major. In C57BL/6 mice, which are resistant to infection, neutrophils are cleared from the site of s.c. infection within 3 days, whereas they persist for at least 10 days in susceptible BALB/c mice. In the present study, we investigated the role of macrophages (MPhi) in regulating neutrophil number. Inflammatory cells were recruited by i.p. injection of either 2% starch or L. major promastigotes. Neutrophils were isolated and cultured in the presence of increasing numbers of MPhi. Extent of neutrophil apoptosis positively correlated with the number of MPhi added. This process was strictly dependent on TNF because MPhi from TNF-deficient mice failed to induce neutrophil apoptosis. Assays using MPhi derived from membrane TNF knock-in mice or cultures in Transwell chambers revealed that contact with MPhi was necessary to induce neutrophil apoptosis, a process requiring expression of membrane TNF. L. major was shown to exacerbate MPhi-induced apoptosis of neutrophils, but BALB/c MPhi were not as potent as C57BL/6 MPhi in this induction. Our results emphasize the importance of MPhi-induced neutrophil apoptosis, and membrane TNF in the early control of inflammation.

Immunoglobulin classes in aquatic mammals. Characterization by serologic cross-reactivity, molecular size and binding of human free secretory component.

On the basis of serologic cross-reactivity, three immunoglobulin classes homologous to human IgG, IgM and IgA were identified in two species of acquatic mammal representing the orders Cetacea (dolphin) and Pinnipedea (sea lion). Molecular size was estimated by sucrose density gradient ultracentrifugation and Sephadex G-200 chromatography, indicating a 7S IgG, 19S IgM and heterogeneous serum IgA. Human secretory component was readily bound to the IgM of both species and to an apparently lesser extent to the larger molecular size populations of IgA. No binding was observed with IgG. Several antisera specific for human γ-chains gave a single precipitin line with the sea lion IgG but when made to react with dolphin serum produced two lines, suggesting the presence of two different subclasses of IgG in this species.

Analysing the innovation process in the EU Integrated Programme, ISAFRUIT

ISAFRUIT is an integrated European Union Project focussed on increasing fruit consumption as a means to improve human health, through evaluating the fruit chain and addressing bottlenecks therein.The innovations which are being developed throughout the ISAFRUIT Project have been analysed to determine both the success factors and the obstacles in reaching the commercialisation stage. Only 9.58% of the deliverables planned within the Project were focussed on developing technological innovations.There is evidence, however, of successes in the development of new innovations arising from the ISAFRUIT Project, with several other potential innovations in the pipeline. Of the technologies identified, 67% are still at the “invention stage”; that is, the stage prior to bridging the so-called “valley of death”, the stage between an invention and an innovation. Those which are considered to have moved over the “valley of death” either had industry partners included in the Project, or had consulted with industry to ensure that the technology was relevant, or met a recognised industry need. Many of the technologies which made less progress did not have the same interactions with industry. A number of other issues were identified which prevented further progress towards innovation. The need for scientists to publish scientific papers, both for their career pathways and to increase their chances of future funding, was identified as one issue, although the filing of patents is now becoming more accepted and recognised. The patenting system is considered complex by many scientists and is not well-understood. Finally, agreements between partners on the sharing of intellectual property rights can cause a delay in the innovation process.