腔内聚乙烯十二指肠-空肠导管对体重调节的作用:猪动物模型可行性研究

目的评估十二指肠-空肠导管（Endoluminal Duodeno-Jejunal Tube，EDJT）在活体猪实验动物模型中减缓体重增加的可行性，及其在中短期生存中的安全性。方法本项研究共用8只45kg重的Yorkshire猪，其中3只置入180emEDJT，1只置入360cm EDJT，另4只猪作为对照组。切开十二指肠，将EDJT导管缝合固定在十二指肠近Vater壶腹起始处。结果评估全部猪的不适反应和体重，每日一次，共7周，未发现严重并发症发生。术后7周3组动物的平均体重变化百分率：对照组、180cm组和360cm组分别是22．5％，6％和-2．8％。EDJT组（180cm组、360cm组）体重增加明显减慢，与对照组相比，有统计学意义（P=0．05）。结论EDJT可以安全使用，无肠梗阻、肠套叠或胰腺炎等并发症发生。EDJT可明显减缓体重增加。     

Computed tomographic study of the posterior condylar angle in arthritic knees: its use in the rotational positioning of the femoral implant of total knee prostheses

The epicondylar axis is a reliable reference to check the rotation of the femoral implant in total knee prostheses (TKPs). However, during the operation it seems easier to use the posterior condylar axis as a landmark. The angle between these two axes is called the posterior condylar angle (PCA). The aim of this study was to measure the PCA in arthritic knees to assess the reliability of the posterior condylar axis as a reference for the control of the rotation of the femoral implant and to look for correlation with other radiological measurements. This prospective study consisted of 103 arthritic knees (81 varus, 22 valgus) before a TKP had been done in 103 patients (75 women, 28 men). The assessment of the PCA was made by computed tomographic scanning (CT). The HKA, HKS and HKT angles were measured on the pangonogram. The posterior condylar axis was internally rotated with respect to the epicondylar axis. The average value for all the patients was 2.65° degrees with a range from 0° to 7°. The PCA was significantly increased in the valgus knees. There was no correlation between the angles on the pangonogram and the posterior condylar axis. While the preoperative assessment of the PCA by CT scanning is reliable, the results obtained indicate the marked variability in its value. If one wishes to use the posterior condylar axis as a guide for rotation, it is therefore necessary to assess the PCA for each patient using adjustable jigs according to the value obtained. No measurement on standard radiographs allowed an extrapolation of the value of the PCA, and CT scanning seems to be the preferable radiological examination.

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Etude tomodensitométrique de l'angle condylien postérieur dans les genoux arthrosiques. Intérêt dans le positionnement en rotation de l'implant fémoral dans les prothèses totales de genou

Résumé L'axe épicondylien est une référence fiable pour le contrôle de la rotation de l'implant fémoral dans les prothèses totales de genou (PTG). Mais, lors de l'intervention, il semble plus facile d'utiliser l'axe condylien postérieur comme repère. L'angle entre ses deux axes est appelé angle condylien postérieur (ACP). Le but de cette étude était de mesurer l'ACP dans les genoux arthrosiques, d'évaluer la fiabilité de l'axe condylien postérieur comme référence pour le réglage de la rotation de l'implant fémoral, de rechercher une corrélation avec d'autres mesures radiologiques. Une étude prospective comportant 103 genoux arthrosiques (81 varus et 22 valgus), avant PTG a été effectuée, chez 103 patients (75 femmes et 28 hommes). L'évaluation de l'ACP a été faite par examen tomodensitométrique (TDM). Les angles HKA, HKS et HKT ont été mesurés sur le pangonogramme. L'axe condylien postérieur était en rotation interne par rapport à l'axe épicondylien. La valeur moyenne pour tous les patients était de 2.65°, avec des valeurs de 0 à 7°. La valeur de l'angle CP augmentait avec une différence significative dans le groupe des genu valgum. Il n'y avait pas de corrélation entre les angles du pangonogramme et l'ACP. Si l'évaluation pré-opératoire de l'ACP par TDM est fiable, les résultats obtenus mettent en évidence une variabilité importante de sa valeur. Il faut donc, si l'on veut utiliser l'axe condylien postérieur comme repère de rotation, évaluer pour chaque patient l'ACP, et utiliser un ancillaire réglable reportant la valeur obtenue. Aucune mesure sur des radiographies standard ne permettant d'extrapoler la valeur de l'ACP, la TDM semble l'examen radiologique de choix.

     

Critical role of multidrug efflux pump CmeABC in bile resistance and in vivo colonization of Campylobacter jejuni

CmeABC functions as a multidrug efflux pump contributing to the resistance of Campylobacter to a broad range of antimicrobials. In this study, we examined the role of CmeABC in bile resistance and its contribution to the adaptation of Campylobacter jejuni in the intestinal tract of the chicken, a natural host and a major reservoir for Campylobacter. Inactivation of cmeABC drastically decreased the resistance of Campylobacter to various bile salts. Addition of choleate (2 mM) in culture medium impaired the in vitro growth of the cmeABC mutants but had no effect on the growth of the wild-type strain. Bile concentration varied in the duodenum, jejunum, and cecum of chicken intestine, and the inhibitory effect of the intestinal extracts on the in vitro growth of Campylobacter was well correlated with the total bile concentration in the individual sections of chicken intestine. When inoculated into chickens, the wild-type strain colonized the birds as early as day 2 postinoculation with a density as high as 10(7) CFU/g of feces. In contrast, the cmeABC mutants failed to colonize any of the inoculated chickens throughout the study. The minimum infective dose for the cmeABC mutant was at least 2.6 x 10(4)-fold higher than that of the wild-type strain. Complementation of the cmeABC mutants with a wild-type cmeABC allele in trans fully restored the in vitro growth in bile-containing media and the in vivo colonization to the levels of the wild-type strain. Immunoblotting analysis indicated that CmeABC is expressed and immunogenic in chickens experimentally infected with C. jejuni. Together, these findings provide compelling evidence that CmeABC, by mediating resistance to bile salts in the intestinal tract, is required for successful colonization of C. jejuni in chickens. Inhibition of CmeABC function may not only control antibiotic resistance but also prevent the in vivo colonization of pathogenic Campylobacter.     

Retinoids induce Fas(CD95) ligand cell surface expression via RARgamma and nur77 in T cells

Cells from the CD4+ murine T hybridoma line IP-12-7 enter the apoptotic suicide program via the Fas ligand (FasL)/Fas-mediated pathway upon TCR stimulation. This stimulus regulates the sensitization of the Fas death pathway and the cell surface appearance of preformed FasL. The apoptosis is dependent on new mRNA and protein synthesis and involves up-regulation of nur77.Two groups of nuclear receptors for retinoic acids (RA) have been identified: retinoic acid receptors (RAR) and retinoid X receptors. IP-12-7 cells express RARalpha and RARgamma. Here we show that,in the IP-12-7 T cells, RA also induced the expression and DNA binding of nur77, and the cell surface appearance of FasL. The induction was mediated via RARgamma. Despite the induced expression of cell surface FasL, only two structurally related RARgamma-selective compounds, CD437 and CD2325, initiated apoptosis in these cells. The lack of apoptosis induction by natural RA was related to the inability of RARgamma to sensitize the Fas death-pathway. Cell surface FasL, however, was able to induce cell death in Fas-bearing target cells. Natural RA also induced the expression of FasL in phytohemagglutinin-activated peripheral murine T cells. It is proposed that therapeutically administered RA might induce apoptosis in Fas-sensitive cells via induction of FasL expression in activated Tcells.     

Comparison of HLA-DR1-restricted T cell response induced in HLA-DR1 transgenic mice deficient for murine MHC class II and HLA-DR1 transgenic mice expressing endogenous murine MHC class II molecules

Transgenic mice expressing human HLA class II molecules provide a useful model for identifying HLA-restricted CD4+ epitopes. However, the influence of endogenous murine H-2-restricted T cell responses on HLA-restricted responses is not known. In the present study, we show that HLA-DR1 transgenic mice deficient for H-2 class II expression (HLA-DR1+/+/IAbeta0/0) exhibit an equivalent expression level of the transgene HLA-DR1 and a similar diversity in the TCR repertoire, but a slightly different number of CD4+ peripheral T cells, when compared to HLA-DR1 transgenic mice in which H-2 class II molecules were retained (HLA-DR1+/+/IAbeta+/+). More importantly, a strong antigen-specific HLA-DR1-restricted response was observed in nearly all HLA-DR1+/+/IAbeta0/0 mice immunized with HBV envelope protein (HBs) or capsid protein (HBc), whereas weak HBs- or HBc-specific HLA-DR1-restricted responses were detected in half of the immunized HLA-DR1+/+/IAbeta+/+ mice. Conversely, strong HBs- or HBc-specific H-2-restricted T cell responses were detected in HLA-DR1+/+/IAbeta+/+ mice but not in HLA-DR1+/+/IAbeta0/0 mice. Our results indicate that the coexpression of endogenous H-2 class II molecules reduces the intensity of HLA-DR1-restricted antigen-specific responses in transgenic mice, by favoring murine over human MHC recognition and education. Thus, HLA-DR1+/+/IAbeta0/0 mice represent a better model for identifying and characterizing HLA-DR1-restricted epitopes relevant for human disease.     

Prediction of AVM obliteration after stereotactic radiotherapy using radiobiological modelling

This study was carried out in order to derive the radiobiological parameters of the dose-response relation for the obliteration of arteriovenous malformation (AVM) following single fraction stereotactic radiotherapy. Furthermore, the accuracy by which the linear Poisson model predicts the probability of obliteration and how the haemorrhage history, location and volume of the AVM influence its radiosensitivity are investigated. The study patient material consists of 85 patients who received radiation for AVM therapy. Radiation-induced AVM obliterations were assessed on the basis of post-irradiation angiographies and other radiological findings. For each patient the dose delivered to the clinical target volume and the clinical treatment outcome were available. These data were used in a maximum likelihood analysis to calculate the best estimates of the parameters of the linear Poisson model. The uncertainties of these parameters were also calculated and their individual influence on the dose-response curve was studied. AVM radiosensitivity was assumed to be the same for all the patients. The radiobiological model used was proved suitable for predicting the treatment outcome pattern of the studied patient material. The radiobiological parameters of the model were calculated for different AVM locations, bleeding histories and AVM sizes. The range of parameter variability had considerable effect on the dose-response curve of AVM. The correlation between the dosimetric data and their corresponding clinical effect could be accurately modelled using the linear Poisson model. The derived response parameters can be introduced into the clinical routine with the calculated accuracy assuming the same methodology in target definition and delineation. The known volume dependence of AVM radiosensitivity was confirmed. Moreover, a trend relating AVM location with its radiosensitivity was observed.     

Complete sparing of high-contrast color input to motion perception in cortical color blindness

It is widely held that color and motion are processed by separate parallel pathways in the visual system, but this view is difficult to reconcile with the fact that motion can be detected in equiluminant stimuli that are defined by color alone. To examine the relationship between color and motion, we tested three patients who had lost their color vision following cortical damage (central achromatopsia). Despite their profound loss in the subjective experience of color and their inability to detect the motion of faint colors, all three subjects showed surprisingly strong responses to high-contrast, moving color stimuli--equal in all respects to the performance of subjects with normal color vision. The pathway from opponent-color detectors in the retina to the motion analysis areas must therefore be independent of the damaged color centers in the occipitotemporal area. It is probably also independent of the motion analysis area MT/V5, because the contribution of color to motion detection in these patients is much stronger than the color response of monkey area MT.     

Increased Production of Interferon‐γ by Leishmania Homologue of the Mammalian Receptor for Activated C Kinase‐Reactive CD4+ T cells among Human Blood Mononuclear Cells: An Early Marker of Exposure to Leishmania?

A prospective study was undertaken to define early predictive immunological marker(s) of exposure to Leishmania in naïve subjects who have never been exposed to any Leishmania and who were also free of any cutaneous leishmaniasis lesions. These naïve subjects could have been exposed to Leishmania in a rain forest where Leishmania guyanensis and their natural vectors and mammalian host are cocirculating. The production of interferon (IFN)‐γ in response to the Leishmania homologue of the mammalian receptor for activated c kinase (LACK), a candidate for vaccine against leishmaniasis was analysed. At the end of their stay in the rain forest, LACK‐specific CD8⁺ T cells were detected in subjects whose peripheral blood mononuclear cell (PBMC) produced IFN‐γ in response to soluble Leishmania antigens (SLA) and in those whose PBMC remained unresponsive to SLA. However, LACK‐specific CD4⁺ T cells were detected only in PBMCs from individuals who became IFN‐γ responders to SLA. In subjects whose PBMC became positive to SLA, LACK‐reactive CD4⁺ T cells producing high level of IFN‐γ were detectable before the SLA‐reactive IFN‐γ producing CD4⁺ T cells, suggesting that the former readout assay could be used as an early predictive immunological marker of exposure to Leishmania in subjects who remained disease free.     

Healthy subjects express differences in clinical responses to inhaled lipopolysaccharide that are related with inflammation and with atopy

BACKGROUND: Endotoxin and its purified derivative LPS are important contaminants of both domestic and occupational environments that have been related to airway diseases. A body of data suggests that there is considerable interindividual variability in LPS sensitivity. OBJECTIVE: The aim of the study was to relate the individual clinical responses to inhaled LPS with the inflammatory process and the atopic status. METHODS: Fifteen healthy subjects were challenged each week by inhalation with saline solution or LPS (0.5, 5, or 50 microg). The systemic response was defined by the increase in body temperature, blood neutrophilia, acute-phase proteins (C-reactive protein and LPS-binding protein [LBP]), and E-selectin. The LPS-induced airway response was defined as the increase in airway responsiveness and related to the cell count and concentration of TNF-alpha, myeloperoxidase, and eosinophil cationic protein in induced sputum. The atopic status was defined as an increase in IgE or a positive skin prick test result. RESULTS: Subjects (n = 7) with a significant increase in body temperature had a larger increase in the systemic inflammatory response (blood neutrophilia; P <.01) and in blood concentrations of C-reactive protein (P <.02) and LBP (P <.01). Subjects with a significant increase in airway responsiveness (n = 8) had an increase in the sputum concentration of eosinophil cationic protein (P <.01). The amplitude of the systemic response (increase in body temperature [P <.001], blood neutrophilia [P <.02], and rise in LBP [P <.05] and decrease in FEV(1) [P <.01]) were inversely associated with the atopic status, suggesting a link between atopy and LPS responsiveness. CONCLUSIONS: The clinical response to LPS occurs systemically or locally and is associated with inflammation. The atopic status was inversely related to the systemic inflammation.