Le fixateur externe dans les lésions traumatiques graves du bassin: résultats à propos de 20 cas consécutifs [External fixator in severe traumatic injuries of the pelvis: results apropos of 20 consecutive cases]

From August 91 to December 94, 20 external fixators were used for severely injured patients (avg. ISS 25.2). The fractures were essentially open book with or without lateral compression and vertical lesions. The indication for fixation was treatment of shock and stabilization in 8 cases, stabilization alone in 9 cases, and in 3 cases as complementary fixation after internal fixation of posterior lesions. The fixation of the pelvis was effective on the amount of blood loss. One acetabulum fracture required surgery, two patients had internal fixation for loss of reduction and two others for late pubic and posterior pain. The clinical results are good; they are more related to the severity of the initial lesion than to the mode of fixation or the quality of the reduction. No superficial sepsis or osteitis was observed in relation to the pins.

Secretory IgA, a major immunoglobulin in most bovine external secretions.

Bovine secretory IgA (SIgA), recently identified in colostrum, was shown to be homologous to human SIgA by immunologic cross-reaction. A quantitative study indicated that bovine SIgA, a minor component of colostrum, is a major immunoglobulin in most other external secretions including saliva, spermatic fluid, lacrimal, nasal and gastrointestinal secretions. SIgA was isolated from saliva. The free form of secretory component was found to be abundant in milk. A normal lactating cow produces about 1.2 g of this protein per day. Two forms of IgA were identified in serum: a normal serum IgA with no secretory antigenic determinant, and a small amount of SIgA. In vitro synthesis of SIgA by the salivary gland was studied by tissue cultures with incorporation of labeled amino acids.

Reemergence of dormant Coats disease after 30 years.

Purpose. We describe an atypical case of a patient with Coats disease that re-emerged after 30 years, illustrating a previously poorly understood long-term evolution of the disease. Methods. A 20-year-old man consulted for visual acuity (VA) decrease in the left eye (LE) to 0.3. Fundus examination revealed an exudative lesion with telangiectasias in the superior peripheral retina compatible with the diagnosis of Coats disease. Results. The patient was treated with cryotherapy and argon laser. Visual acuity improved to 0.5 and remained stable during a 1-year follow-up. The patient did not seek further clinical follow-up. Thirty years later, he returned complaining of a progressive VA decrease in the LE. Snellen VA was measured to counting fingers. Fundus examination revealed stage 3A Coats disease with macular exudation and a serous retinal detachment in the inferior quadrants requiring the placement of an encircling band, external drainage, and cryotherapy of the vascular lesions. After 10 additional sessions of argon laser on the vascular malformations, exudation regressed further and best-corrected VA increased to 0.1 at the end of the follow-up period. Conclusions. Coats disease must be considered as a chronic disease, which necessitates a very long-term follow-up even in the absence of subjective visual loss. The disease can reawaken and recur with force in previously unaffected areas of the retina several decades later. The gold standard treatment consists of cryotherapy and argon laser. However, in cases of very important retinal exudation, surgical management with subretinal drainage may be necessary.

Pin guidance of reconstruction plate contour: an expanded role of external fixation

This article presents a modification of intraoperative external fixation for mandibular reconstruction with free tissue flaps. This technique is indicated when preregistration of the reconstruction plate is not possible due to transmandibular tumor extension. Once standard external fixation has been carried out and prior to segmental mandibulectomy, additional pins are fixed to the connecting rod that delineate the mandibular contour in three-dimensional (3D) space. Following mandibulectomy, these pins allow accurate contouring of the reconstruction plate and improved restoration of mandibular contour, projection, and dental occlusion. A step-by-step description of the technique using models and intraoperative photos is presented. This method of mandibular reconstruction is a simple and time-effective alternative to intraoperative computer navigation and 3D modeling in select cases of oral carcinoma where tumor infiltration of the outer mandibular cortex precludes prebending of the reconstruction plates.

Adaptive tuning of perceptual timing to whole body motion.

In a previous work we have shown that sinusoidal whole-body rotations producing continuous vestibular stimulation, affected the timing of motor responses as assessed with a paced finger tapping (PFT) task (Binetti et al. (2010). Neuropsychologia, 48(6), 1842-1852). Here, in two new psychophysical experiments, one purely perceptual and one with both sensory and motor components, we explored the relationship between body motion/vestibular stimulation and perceived timing of acoustic events. In experiment 1, participants were required to discriminate sequences of acoustic tones endowed with different degrees of acceleration or deceleration. In this experiment we found that a tone sequence presented during acceleratory whole-body rotations required a progressive increase in rate in order to be considered temporally regular, consistent with the idea of an increase in "clock" frequency and of an overestimation of time. In experiment 2 participants produced self-paced taps, which entailed an acoustic feedback. We found that tapping frequency in this task was affected by periodic motion by means of anticipatory and congruent (in-phase) fluctuations irrespective of the self-generated sensory feedback. On the other hand, synchronizing taps to an external rhythm determined a completely opposite modulation (delayed/counter-phase). Overall this study shows that body displacements "remap" our metric of time, affecting not only motor output but also sensory input.

A treatment planning method for sequentially combining radiopharmaceutical therapy and external radiation therapy.

PURPOSE: Effective cancer treatment generally requires combination therapy. The combination of external beam therapy (XRT) with radiopharmaceutical therapy (RPT) requires accurate three-dimensional dose calculations to avoid toxicity and evaluate efficacy. We have developed and tested a treatment planning method, using the patient-specific three-dimensional dosimetry package 3D-RD, for sequentially combined RPT/XRT therapy designed to limit toxicity to organs at risk. METHODS AND MATERIALS: The biologic effective dose (BED) was used to translate voxelized RPT absorbed dose (D(RPT)) values into a normalized total dose (or equivalent 2-Gy-fraction XRT absorbed dose), NTD(RPT) map. The BED was calculated numerically using an algorithmic approach, which enabled a more accurate calculation of BED and NTD(RPT). A treatment plan from the combined Samarium-153 and external beam was designed that would deliver a tumoricidal dose while delivering no more than 50 Gy of NTD(sum) to the spinal cord of a patient with a paraspinal tumor. RESULTS: The average voxel NTD(RPT) to tumor from RPT was 22.6 Gy (range, 1-85 Gy); the maximum spinal cord voxel NTD(RPT) from RPT was 6.8 Gy. The combined therapy NTD(sum) to tumor was 71.5 Gy (range, 40-135 Gy) for a maximum voxel spinal cord NTD(sum) equal to the maximum tolerated dose of 50 Gy. CONCLUSIONS: A method that enables real-time treatment planning of combined RPT-XRT has been developed. By implementing a more generalized conversion between the dose values from the two modalities and an activity-based treatment of partial volume effects, the reliability of combination therapy treatment planning has been expanded.

Sidebranching induced by external noise in solutal dendritic growth

We have studied sidebranching induced by fluctuations in dendritic growth. The amplitude of sidebranching induced by internal (equilibrium) concentration fluctuations in the case of solidification with solutal diffusion is computed. This amplitude turns out to be significantly smaller than values reported in previous experiments. The effects of other possible sources of fluctuations (of an external origin) are examined by introducing nonconserved noise in a phase-field model. This reproduces the characteristics of sidebranching found in experiments. Results also show that sidebranching induced by external noise is qualitatively similar to that of internal noise, and it is only distinguished by its amplitude.

The early IL-4 response to Leishmania major responsible for progressive disease in BALB/c mice is subject to the control of autocrine IL-2 production and regulatory CD4+C25+ T cells

Résumé : La majorité des souches de souris de laboratoire sont résistantes à l'infection par le parasite Leishmania major (L. major). A l'opposé, les souris de la souche BALB développent une maladie évolutive. La résistance et la sensibilité sont corrélées avec l'apparition de lymphocytes T CD4+ spécifiques du parasite, Th1 (de l'anglais T helper) ou Th2 respectivement. La réponse aberrante Th2 chez les souris de la souche BALB/c dépend, au moins en partie, de façon critique de la production rapide d'IL-4 suite à l'infection. Ce pic précoce d'IL-4 est produit par une population de lymphocytes T CD4+ restreinte aux molécules du MHC de classe II, exprimant les chaînes du récepteur des cellules T Vß4-Va8. Ces lymphocytes sont spécifiques d'un épitope de l'homologue Leishmania de la molécule RACK1 des mammifères, appelée LACK. Il a été clairement démontré que l'IL-4 rapidement produite par ces cellules T CD4+ Vß4-Va8 induit la maturation Th2 responsable de la sensibilité vis-à-vis de L. major. Des expériences ont été entreprises pour étudier la régulation de cette réponse précoce d'IL-4. Dans ce travail, nous avons documenté, dans les cellules provenant des ganglions de souris sensibles infectées par L. major, une augmentation de la transcription de l'ARNm de l'IL-2 qui précède la réponse précoce d'IL-4. La neutralisation de l'IL-2 durant les premiers jours d'infection induit la maturation des cellules Thl et la résistance vis-à-vis de L. major. Ces effets de l'anticorps anti-IL-2 neutralisant sont liés à sa capacité d'interférer avec la transcription rapide d'IL-4 des cellules CD4+ réactives à l'antigène LACK. Une augmentation similaire d'IL-2 survient chez les souris résistantes C57BL/6 qui sont incapables de générer la réponse précoce d'IL-4. Cependant, la protéiné LACK induit une transcription précoce d'IL-2 uniquement chez les souris sensibles. Des expériences de reconstitution utilisant des souris C.B.-17 SCID et des cellules T CD4+ réactives à LACK provenant de souris BALB/c IL-2-~démontrent un mode d'action autocrine de l'IL-2 sur la régulation de la réponse précoce d'IL4. Par conséquent, chez les souris C57BL/6, l'absence du pic précoce d'ARNm de l'IL-4 important pour la progression de la maladie paraît liée à l'incapacité des cellules T CD4+ réactives à LACK de produire de l'IL-2. Un rôle dans le contrôle de la production précoce d'IL-4 par les cellules T régulatrices CD4+CD25+ a été investigué en déplétant in vivo cette population de cellules. La déplétion induit une élévation du pic précoce de l'ARNm de l'IL-4 dans les ganglions drainant de souris BALB/c, ainsi qu'une exacerbation du cours de la maladie avec des taux augmentés d'IL-4 dans les ganglions. La réponse rapide d'IL-2 vis-à-vis de L. major est aussi significativement augmentée chez les souris BALB/c déplétées en cellules CD4+CD25+. De plus, nous avons démontré que le transfert de 10puissance(7) cellules provenant de la rate de souris BALB/c déplétées en cellules T régulatrices CD4+CD25+ rend les souris SCID sensibles à l'infection et permet la différentiation Th2. Au contraire, les souris SCID reconstituées avec 10' cellules de la rate de souris BALB/c contrôle sont résistantes à infection par L. major et développent une réponse Thl. Chez les souris SCID reconstituées avec des cellules de rate déplétées en cellules exprimant le marqueur CD25, le traitement avec un anticorps neutralisant l'IL-4 au moment de l'infection par L. major prévient le développement de la réponse Th2 et rend ces souris résistantes à l'infection. Ces résultats démontrent que les cellules T régulatrices CD4+CD25+ jouent un rôle dans la régulation du pic précoce d'IL-4 responsable du développement cellulaire Th2 dans ce modèle d'infection. Summary Mice from most strains are resistant to infection with Leishmania major (L. major). In contrast, BALB mice develop progressive disease. Resistance and susceptibility result from parasite-specific CD4+ Thl or Th2 cells, respectively. The aberrant Th2 response in BALB/c mice depends, at least in part, upon the production of IL-4 early after infection. The CD4+ T cells responsible for this early IL-4 response to L. major express a restricted TCR repertoire (Vß4-Va8) and respond to an I-Ad-restricted epitope of the Leishmania homologue of mammalian RACK1, designated LACK. The role of these cells and the IL-4 they produce for subsequent Th2 cell development and disease progression in BALB/c mice was demonstrated. Experiments have been undertaken to study the regulation of the rapid IL-4 production to L. major. In this report, we document an IL-2 mRNA burst, preceding the reported early IL-4 response, in draining lymph nodes of susceptible mice infected with L. major. Neutralization of IL-2 during the first days of infection redirected Thl cell maturation and resistance to L. major, through interference with the rapid IL-4 transcription in LACKreactive CD4+ cells. A burst of IL-2 transcripts also occurred in infected C57BL/6 mice that do not mount an early IL-4 response. However, although the LACK protein induced IL-2 transcripts in susceptible mice, it failed to trigger this response in resistant C57BL/6 mice. Reconstitution experiments using C.B.-17 SCID mice and LACK-reactive CD4+ T cells from IL-2-/- BALB/c mice showed that triggering of the early IL-4 response required autocrine IL2. Thus, in C57BL/6 mice, the inability of LACK-reactive CD4+ T cells to express early IL-4 mRNA transcription, important for disease progression, appears due to an incapacity of these cells to produce IL-2. A role for CD4+CD25+ regulatory T cells in the control of this early IL-4 production was investigated by depleting in vivo this regulatory T cell population. Depletion induced an increase in the early burst of IL-4 mRNA in the draining lymph nodes of BALB/c mice, and exacerbated the course of disease with higher levels of IL-4 mRNA and protein in their lymph nodes. The rapid IL-2 response to L. major is also significantly enhanced in BALB/c mice depleted of CD4+CD25+ cells. We further showed that transfer of 10~ BALB/c spleen cells that were depleted of CD4+CD25+ regulatory T cells rendered SCID mice susceptible to infection and allowed Th2 differentiation while SCID mice reconstituted with 10 control BALB/c spleen cells were resistant to infection with L. major and developed a Thl response. Treatment with a mAb against IL-4 upon infection with L. major in SCID mice reconstituted with CD25-depleted spleen cells prevented the development of Th2 polarization and rendered them resistant to infection. These results demonstrate that CD4+CD25+ regulatory T cells play a role in regulating the early IL-4 mRNA and the subsequent development of a Th2 response in this model of infection.

Oxidation of methane at the CH4/H2O-(CO2) transition zone in the external part of the Central Alps, Switzerland: Evidence from stable isotope investigations

With the aim of understanding the mechanisms that control the metamorphic transition from the CH4- to the H2O-(CO2)-dominated fluid zone in the Helvetic domain of the Central Alps of Switzerland, fluid inclusions in quartz, illite ``crystallinity'' index, vitrinite reflectance, and the stable isotope compositions of vein and whole rock minerals and fluids trapped in quartz were investigated along four cross-sections. Increasing temperature during prograde metamorphism led to the formation of dry gas by hydrocarbon cracking in the CH4-zone. Fluid immiscibility in the H2O-CH4-(CO2)-NaCl system resulted in cogenetic, CH4- and H2O-dominated fluid inclusions. In the CH4-zone, fluids were trapped at temperatures <= 270 +/- 5 degrees C. The end of the CH4-zone is markedby a sudden increase of CO2 content in the gas phase of fluid inclusions. At temperatures > 270 +/- 5 degrees C, in the H2O-zone, the total amount of volatiles within the fluid decreased below 1 mol% with no immiscibility. This resulted m total homogenization temperatures of H2O-(CO2-CH4)-NaCl inclusions below 180 degrees C. Hydrogen isotope compositions of methane in fluid inclusion have delta D values of less than -100 parts per thousand in the CH4-zone, typical for an origin through cracking of higher hydrocarbons, but where the methane has not equilibrated with the pore water. delta D values of fluid inclusion water are around -40 parts per thousand., in isotopic equilibrium with phyllosilicates of the whole rocks. Within the CH4 to H2O(CO2) transition zone, delta D(H2O) values in fluid inclusions decrease to -130 parts per thousand interpreted to reflect the contribution of deuterium depleted water from methane oxidation. In the H2O-zone, delta D(H2O) values increase again towards an average of -30 parts per thousand which is again consistent with isotopic equilibrium with host-rock phyllosilicates. delta C-13 values of methane in fluid inclusions from the CH4-zone are around -27 parts per thousand in isotopic equilibrium with calcite in veins and whole rocks. The delta C-13(CH4) values decrease to less than -35 parts per thousand at the transition to the H2O-zone and are no longer in equilibrium with the carbonates in the whole rocks. delta C-13 values of CO, are variable but too low to be in equilibrium with the wall rock fluids, compatible with a contribution of CO2 from closed system oxidation of methane. Differences in isotopic composition between host-rock and Alpine fissure carbonate are generally small, suggesting that the amount of CO2 produced by oxidation of methane was small compared to the C-budget in the rocks and local pore fluids were buffered by the wall rocks during precipitation of calcite within the fissures. (c) 2006 Elsevier B.V. All rights reserved.

A comparison of Bayesian and frequentist approaches to incorporating external information for the prediction of prostate cancer risk.

We present the most comprehensive comparison to date of the predictive benefit of genetics in addition to currently used clinical variables, using genotype data for 33 single-nucleotide polymorphisms (SNPs) in 1,547 Caucasian men from the placebo arm of the REduction by DUtasteride of prostate Cancer Events (REDUCE®) trial. Moreover, we conducted a detailed comparison of three techniques for incorporating genetics into clinical risk prediction. The first method was a standard logistic regression model, which included separate terms for the clinical covariates and for each of the genetic markers. This approach ignores a substantial amount of external information concerning effect sizes for these Genome Wide Association Study (GWAS)-replicated SNPs. The second and third methods investigated two possible approaches to incorporating meta-analysed external SNP effect estimates - one via a weighted PCa 'risk' score based solely on the meta analysis estimates, and the other incorporating both the current and prior data via informative priors in a Bayesian logistic regression model. All methods demonstrated a slight improvement in predictive performance upon incorporation of genetics. The two methods that incorporated external information showed the greatest receiver-operating-characteristic AUCs increase from 0.61 to 0.64. The value of our methods comparison is likely to lie in observations of performance similarities, rather than difference, between three approaches of very different resource requirements. The two methods that included external information performed best, but only marginally despite substantial differences in complexity.

Incidence and outcome of progressive multifocal leukoencephalopathy over 20 years of the Swiss HIV Cohort Study.

BACKGROUND: We investigated the incidence and outcome of progressive multifocal leukoencephalopathy (PML) in human immunodeficiency virus (HIV)-infected individuals before and after the introduction of combination antiretroviral therapy (cART) in 1996. METHODS: From 1988 through 2007, 226 cases of PML were reported to the Swiss HIV Cohort Study. By chart review, we confirmed 186 cases and recorded all-cause and PML-attributable mortality. For the survival analysis, 25 patients with postmortem diagnosis and 2 without CD4+ T cell counts were excluded, leaving a total of 159 patients (89 before 1996 and 70 during 1996-2007). RESULTS: The incidence rate of PML decreased from 0.24 cases per 100 patient-years (PY; 95% confidence interval [CI], 0.20-0.29 cases per 100 PY) before 1996 to 0.06 cases per 100 PY (95% CI, 0.04-0.10 cases per 100 PY) from 1996 onward. Patients who received a diagnosis before 1996 had a higher frequency of prior acquired immunodeficiency syndrome-defining conditions (P = .007) but similar CD4+ T cell counts (60 vs. 71 cells/microL; P = .25), compared with patients who received a diagnosis during 1996 or thereafter. The median time to PML-attributable death was 71 days (interquartile range, 44-140 days), compared with 90 days (interquartile range, 54-313 days) for all-cause mortality. The PML-attributable 1-year mortality rate decreased from 82.3 cases per 100 PY (95% CI, 58.8-115.1 cases per 100 PY) during the pre-cART era to 37.6 cases per 100 PY (95% CI, 23.4.-60.5 cases per 100 PY) during the cART era. In multivariate models, cART was the only factor associated with lower PML-attributable mortality (hazard ratio, 0.18; 95% CI, 0.07-0.50; P < .001), whereas all-cause mortality was associated with baseline CD4+ T cell count (hazard ratio per increase of 100 cells/microL, 0.52; 95% CI, 0.32-0.85; P = .010) and cART use (hazard ratio, 0.37; 95% CI, 0.19-0.75; P = .006). CONCLUSIONS: cART reduced the incidence and PML-attributable 1-year mortality, regardless of baseline CD4+ T cell count, whereas overall mortality was dependent on cART use and baseline CD4+ T cell count.

Myéloradiculopathie chronique progressive chez un homme de 61 ans [Chronic progressive myeloradiculopathy in a 61-year-old man]

A painful worsening of known difficulties in walking led us to investigate a man who presented a spastic paraparesis. Radiological investigations had to be repeated three times before making a diagnosis of a right C6 spinal dural arteriovenous fistula after a 22-month follow-up. Knowing the mechanisms leading to spinal venous hypertension may explain the low yield of the early radiological investigations that should be repeated. The efficiency of the treatment depends on the severity of the presurgical neurologic manifestations.

Rhythmic growth explained by coincidence between internal and external cues.

Most organisms use circadian oscillators to coordinate physiological and developmental processes such as growth with predictable daily environmental changes like sunrise and sunset. The importance of such coordination is highlighted by studies showing that circadian dysfunction causes reduced fitness in bacteria and plants, as well as sleep and psychological disorders in humans. Plant cell growth requires energy and water-factors that oscillate owing to diurnal environmental changes. Indeed, two important factors controlling stem growth are the internal circadian oscillator and external light levels. However, most circadian studies have been performed in constant conditions, precluding mechanistic study of interactions between the clock and diurnal variation in the environment. Studies of stem elongation in diurnal conditions have revealed complex growth patterns, but no mechanism has been described. Here we show that the growth phase of Arabidopsis seedlings in diurnal light conditions is shifted 8-12 h relative to plants in continuous light, and we describe a mechanism underlying this environmental response. We find that the clock regulates transcript levels of two basic helix-loop-helix genes, phytochrome-interacting factor 4 (PIF4) and PIF5, whereas light regulates their protein abundance. These genes function as positive growth regulators; the coincidence of high transcript levels (by the clock) and protein accumulation (in the dark) allows them to promote plant growth at the end of the night. Thus, these two genes integrate clock and light signalling, and their coordinated regulation explains the observed diurnal growth rhythms. This interaction may serve as a paradigm for understanding how endogenous and environmental signals cooperate to control other processes.