Predictive Value for Outcome and Evolution of Geriatric Parameters after Transcatheter Aortic Valve Implantation

To identify parameters of comprehensive geriatric assessment (CGA) CGA including ABCDEF score, a multidomain frailty assessment, associated with poor outcome after TAVI and to assess the evolution of CGA parameters at 6-months follow-up. One-year monocentric prospective cohort study. Departments of geriatric medicine and cardiology in Rouen University Hospital, Normandy, France. All patients over 70, selected for TAVI by a multidisciplinary “heart team”. 8-areas CGA was performed before TAVI and at 6-months follow-up. Poor outcome was defined as decrease in 1 BADL or unplanned readmission at 6 months or death within the first year after TAVI. Geriatric characteristics associated with poor outcome were assessed by logistic regression with surgical scores as bivariable. Geriatric characteristics were compared between baseline and 6-months follow-up. 114 patients (mean age 85.8±5.3 years) were included. Mean EuroSCORE was 19.1±10.6%. Poor outcome occurred in 57(50.0%) patients. Loss of one BADL (OR: 1.66, 95CI[1.11–2.48]), decrease in IADL (OR: 1.41, 95CI[1.14–1.74]), in plasmatic albumin (OR: 1.10, 95CI[1.01–1.20]), in MMSe (OR: 1.13, 95CI[1.02–1.26]), low walking speed (OR: 1.53, 95CI[1.01–2.33]) and ABCDEF score ≥2 (OR: 1.63, 95CI[1.09–2.42]) were independently associated with poor outcome. In survivors with complete follow-up (n=80), most geriatric parameters were maintained 6 months after TAVI, but IADL decreased (5.6±1.9 to 4.9±2.2, p<0.001). MMSe increased in patients with previous cognitive impairments whereas it decreased in those without (p<0.001). CGA parameters are independently associated with poor outcome after TAVI. These parameters, but IADL, are maintained at 6 months and course of the MMSe depends on previous cognitive status.     

Twenty years of FISH-based translocation analysis for retrospective ionizing radiation biodosimetry

Purpose: The fluorescent in situ hybridization (FISH) technique, which easily detects reciprocal translocations, is currently used to estimate doses in retrospective biological dosimetry, after suspected accidental overexposure to ionizing radiation (IR). This study of 42 cases aimed to verify the appropriateness of this assay for radiation dose reconstruction, compared to the dicentric assay, and to evaluate other limitations.

Material and methods: We labeled chromosomes 2, 4, and 12 by 3-color FISH painting to detect translocations on lymphocytes of patients with suspected past IR overexposure.

Result: Translocation dose estimation showed doses significantly different from 0?Gy in 25 of the 42 cases. The lowest positive dose measured was 0.3?Gy. Several months after IR exposure, the doses measured by translocation and dicentric assays are quite similar. For a year, dose estimation by translocation assay becomes more relevant as dicentric frequency starts to decrease, coming close to 0 for more than a year after the exposure. The persistence of translocations enabled us to corroborate an overexposure 44 years earlier. Interpretation of the observed translocation yield requires the knowledge of the patient’s other radiation exposures. A dose assessment by this biomarker is relevant only if the radiation exposure is confirmed.

Conclusions: This technique is appropriate for corroborating a former IR exposure of individuals. When the radiation dose is greater than 1?Gy, the translocations in complex exchanges must be considered. Another relevant point is the use of an appropriate background yield of translocations. The dose assessment, however, also depends on exposure to various genotoxic agents besides IR. If no evidence about the existence of radiation exposure is available, dose assessment is not useful. For this reason, report only the translocation frequency and its comparison with the background yield by age class is preferable.     

Modulation of vascular tone and reactivity by nitric oxide in porcine pulmonary arteries and veins

Isolated porcine pulmonary vessels were studied in order to evaluate the role of nitric oxide in arteries and veins. Leukotriene C4 and noradrenaline contracted porcine pulmonary arteries but induced only negligible contractions of porcine pulmonary veins. After treatment with the nitric oxide synthase inhibitor N(omega)-nitro-L-arginine (L-NOARG), significant contractions to leukotriene C4 and noradrenaline were uncovered in pulmonary veins. In arterial preparations, L-NOARG caused a less marked potentiation of noradrenaline-induced contractions and did not alter leukotriene C4-induced contractions. Endothelium-dependent relaxations to acetylcholine were greater in veins compared with arteries whereas the endothelium-independent relaxations to the nitric oxide donor sodium nitroprusside (SNP) and the cyclic nucleotide analogue 8-bromo-cGMP were similar in the two preparations. Taken together these data suggest that the apparent insensitivity of porcine pulmonary veins to leukotriene C4 and noradrenaline was because of release of nitric oxide. The effect of nitric oxide synthase inhibition was less pronounced in porcine pulmonary arteries, suggesting a preferential functional role of nitric oxide in porcine pulmonary veins, originating in a greater production of nitric oxide by veins as opposed to arteries.     

Immunohistochemical evidence for the expression of the carcinoembryonic antigen by human thymic epithelial cells in vitro and in neoplastic conditions.

Thymic epithelial cells (TECs), which are known to influence T-cell differentiation, may undergo phenotypic changes and lose some differentiation antigens (for example, the HLA-DR complex) in neoplastic conditions and when they are grown in culture. Using an indirect immunofluorescence assay, the authors investigated the expression of the carcinoembryonic antigen (CEA) by normal cultured or pathologic human TECs. This antigen, which can be regarded as a marker of undifferentiation, disappears during the normal development of epithelial tissues and reappears in neoplastic conditions. In normal as well as hyperplastic (myasthenia gravis-associated) thymuses, the epithelial network (revealed in double-labeling experiments by an anti-keratin monoclonal antibody) is virtually CEA-negative, except for the specific labeling observed on some cells of Hassall's corpuscles. In thymomatous epithelial cells, however, a strong and specific fluorescent labeling was consistently detected in all thymomas studied. Thymic epithelial cells grown in cultures from fragments of normal thymuses also expressed CEA on their cell membranes. Interestingly, the relative number of CEA-positive cells increased as a function of the age of the primary culture and reached virtually 100% when monolayers became confluent (Days 12-14). Moreover, using an ELISA assay, the authors demonstrated the presence of CEA in supernatants from TEC cultures. Interestingly, the amount of CEA in these supernatants decreased as a function of the age of the culture. In addition, a marked inhibition of TEC proliferation was observed after treating the cultures with an anti-CEA serum. Our results demonstrate that CEA is expressed not only in situ by differentiated neoplastic TECs but also by normal TECs cultured in vitro. In addition, the inhibitory action of the anti-CEA serum on TEC proliferation suggests that CEA may act physiologically as a growth factor for proliferating epithelial cells. In this respect, cultures of human TECs represent a good model for further studies.     

Immunomodulation by roquinimex decreases the expression of IL-23 (p19) mRNA in the brains of herpes simplex virus type 1 infected BALB/c mice

Herpes simplex virus (HSV) is a common neurotropic virus which infects epithelial cells and subsequently the trigeminal ganglia (TG) and brain tissue. We studied how immunomodulation with roquinimex (Linomide) affects the course of corneal HSV infection in BALB/c mice. BALB/c mice have also been used in a model for HSV-based vectors in treating an autoimmune disease of the central nervous system (CNS). We addressed the questions of how immunomodulation affects the local as well as the systemic immune response and whether roquinimex could facilitate the spread of HSV to the CNS. The cytokine response in the brain and TG was studied using a quantitative rapid real-time RT-PCR method. We were interested in whether immunomodulation affects the expression of the recently described Th1-cytokine IL-23p19 in the brain and TG. The expression of IL-23 mRNA was decreased in brains of roquinimex-treated BALB/c mice. Also the expression of IL-12p35 and IFN-gamma mRNAs decreased. No significant changes were seen in IL-4 and IL-10 mRNA expression. The cytokine response was also studied using supernatants of stimulated splenocytes by EIA. Roquinimex treatment suppressed the production of IFN-gamma and also the production of IL-10 in HSV-infected BALB/c mice.