Foam sclerotherapy combined with surgical treatment for recurrent varicose veins: short term results.

OBJECTIVE: To study the short term results of combined peroperative foam sclerotherapy (PFS) and surgical treatment for recurrent varicose veins. METHODS: PFS was used to treat 129 limbs with recurrent varices: 100 great saphenous (GSV), 29 small saphenous veins (SSV). Foam was prepared with 1% polidocanol mixed with 4 times its volume of air. The 100 GSVs comprised 28 trunks directly connected with the femoral vein, 28 connected to a lymph node venous network, 11 associated with perforators and 33 isolated trunks. The 29 SSVs comprised 4 trunks directly connected to the popliteal vein, 7 isolated trunks, 15 popliteal perforators and 3 recanalisations after SSV stripping. All operations included phlebectomies. In twenty limbs re-ligation of the SFJ and 4 SPJs was carried out. All were performed under local anaesthesia in an ambulatory setting. Patients were assessed clinically and by colour duplex ultrasound after 3 and 40 days follow-up. RESULTS: 120 patients (93%) showed complete obliteration of saphenous trunks, junctions and varices. The 9 incomplete obliterations were 3 venous recanalisations in the SSV compartment and 6 perforators (4 popliteal and 2 femoral). Two asymptomatic deep venous thromboses were detected by colour duplex 3 days after operation. CONCLUSION: PFS facilitates surgical treatment of recurrent varicose veins. There is a small risk of post-operative deep vein thrombosis.     

LARP7 variants and further delineation of the Alazami syndrome phenotypic spectrum among primordial dwarfisms: 2 sisters

Alazami syndrome (AS) (MIM# 615071) is an autosomal recessive microcephalic primordial dwarfism (PD) with recognizable facial features and severe intellectual disability due to depletion or loss of function variants in LARP7. To date, 15 patients with AS have been reported. Here we describe two consanguineous Algerian sisters with Alazami PD due to LARP7 homozygous pathogenic variants detected by whole exome sequencing. By comparing these two additional cases with those previously reported, we strengthen the key features of AS: severe growth restriction, severe intellectual disability and some distinguishing facial features such as broad nose, malar hypoplasia, wide mouth, full lips and abnormally set teeth. We also report significant new findings enabling further delineation of this syndrome: disproportionately mild microcephaly, stereotypic hand wringing and severe anxiety, thickened skin over the hands and feet, and skeletal, eye and heart malformations. From previous reviews, we summarize the main etiologies of PD according to the involved mechanisms and cellular pathways, highlighting their clinical core features.     

Chemokine transport across human vascular endothelial cells.

Leukocyte migration across vascular endothelium is mediated by chemokines that are either synthesized by the endothelium or transferred across the endothelium from the tissue. The mechanism of transfer of two chemokines, CXCL10 (interferon gamma-inducible protein [IP]-10) and CCL2 (macrophage chemotactic protein [MCP]-1), was compared across dermal and lung microvessel endothelium and saphenous vein endothelium. The rate of transfer depended on both the type of endothelium and the chemokine. The permeability coefficient (Pe) for CCL2 movement across saphenous vein was twice the value for dermal endothelium and four times that for lung endothelium. In contrast, the Pe value for CXCL10 was lower for saphenous vein endothelium than the other endothelia. The differences in transfer rate between endothelia was not related to variation in paracellular permeability using a paracellular tracer, inulin, and immunoelectron microscopy showed that CXCL10 was transferred from the basal membrane in a vesicular compartment, before distribution to the apical membrane. Although all three endothelia expressed high levels of the receptor for CXCL10 (CXCR3), the transfer was not readily saturable and did not appear to be receptor dependent. After 30 min, the chemokine started to be reinternalized from the apical membrane in clathrin-coated vesicles. The data suggest a model for chemokine transcytosis, with a separate pathway for clearance of the apical surface.     

Quantitative comparison between two phase contrast techniques: diffraction enhanced imaging and phase propagation imaging

Two x-ray phase contrast imaging techniques are compared in a quantitative way for future mammographic applications: diffraction enhanced imaging (DEI) and phase propagation imaging (PPI). DEI involves, downstream of the sample, an analyser crystal acting as an angular filter for x-rays refracted by the sample. PPI simply uses the propagation (Fresnel diffraction) of the monochromatic and partially coherent x-ray beam over large distances. The information given by the two techniques is assessed by theoretical simulations and compared at the level of the experimental results for different kinds of samples (phantoms and real tissues). The imaging parameters such as the energy, the angular position of the analyser crystal in the DEI case or the sample to detector distance in the PPI case were varied in order to optimize the image quality in terms of contrast, visibility and figure of merit.     

Fish Hydrolysate Supplementation Containing n-3 Long Chain Polyunsaturated Fatty Acids and Peptides Prevents LPS-Induced Neuroinflammation

Neuroinflammation constitutes a normal part of the brain immune response orchestrated by microglial cells. However, a sustained and uncontrolled production of proinflammatory factors together with microglial activation contribute to the onset of a chronic low-grade inflammation, leading to neuronal damage and cognitive as well as behavioral impairments. Hence, limiting brain inflammatory response and improving the resolution of inflammation could be particularly of interest to prevent these alterations. Dietary n-3 long chain polyunsaturated fatty acids (LC-PUFAs) and low molecular weight peptides are good candidates because of their immunomodulatory and proresolutive properties. These compounds are present in a fish hydrolysate derived from marine-derived byproducts. In this study, we compared the effect of an 18-day supplementation with this fish hydrolysate to a supplementation with docosahexaenoic acid (DHA) on lipopolysaccharide (LPS)-induced inflammation in mice. In response to peripherally injected LPS, the fish hydrolysate supplementation decreased the hippocampal mRNA expression of the proinflammatory cytokines IL-6 (p < 0.001), IL-1β (p = 0.0008) and TNF-α (p < 0.0001), whereas the DHA supplementation reduced only the expression of IL-6 (p = 0.004). This decline in proinflammatory cytokine expressions was associated with an increase in the protein expression of IκB (p = 0.014 and p = 0.0054 as compared to the DHA supplementation and control groups, respectively) and to a modulation of microglial activation markers in the hippocampus. The beneficial effects of the fish hydrolysate could be due in part to the switch of the hippocampal oxylipin profile towards a more anti-inflammatory profile as compared to the DHA supplementation. Thus, the valorization of fish byproducts seems very attractive to prevent and counteract neuroinflammation.     

Effect of novel environmental stimuli on rat behaviour and central noradrenaline function measured by in vivo microdialysis

Rationale: Although physically aversive stimuli induce functional changes in central noradrenergic neurones, little is known about the noradrenergic response to environmentally aversive stimuli. Objectives: The first aim was to characterise environmental features that are perceived as stressful by rats. The second was to investigate whether changes in the concentration of extracellular noradrenaline are induced by these environmental features. Methods: A light/dark shuttle-box was used to test rats’ behavioural response to a range of stimuli (novelty, bright light, and the presence of an unfamiliar rat), either before or after microdialysis probe implantation. Changes in the concentration of extracellular noradrenaline in the frontal cortex and hypothalamus in vivo were then evaluated on exposure to these same test conditions. Results: Naive rats spent less time in a brightly-lit test arena than a dark one. However, the behavioural response to the light arena was attenuated by the presence of an unfamiliar rat. Probe implantation intensified the response to the light arena but did not affect behaviour in the dark arena. In the microdialysis studies, there was no change in the concentration of extracellular noradrenaline on transfer of rats to the dark arena but there was an increase in both the frontal cortex (+45%) and hypothalamus (+75%) on exposure to the light arena. A similar increase was induced in both brain regions when the light arena contained an unfamiliar rat. Conclusions: Implantation of a microdialysis probe modifies the behavioural responses to certain environmental stimuli. Regardless of this, the extent to which rats perceive a novel environment as aversive is not the only determinant of the noradrenergic response to such stimuli. However, differences in stimulus controllability in the microdialysis and the behavioural experiments could influence the apparent intensity of the stress. Received: 29 October 1998 / Final version: 19 March 1999     

A mechanistic basis for the role of cycle arrest in the genetic toxicology of the dietary carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP).

The heterocyclic amine 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), formed during the cooking of meat, induces tumors of the prostate, colon, and mammary gland when fed to rats. PhIP is readily absorbed and efficiently metabolized to a genotoxic derivative by CYP1 enzymes. Although metabolism and mutational potential of PhIP have previously been well characterized, the intervening cellular and genomic responses to the chemical are not fully understood. We have examined the cellular response to PhIP exposure in human mammary epithelial MCF10A cells, which retain characteristics of normal breast epithelial cells. Because these cells fail to activate PhIP, they were cocultured with a human lymphoblastoid cell line MCL-5, which constitutively expresses CYP1A1, and have been transfected to express human CYPs1A2, 2A6, 3A4, and 2E1. The MCL-5 cells were irradiated (2,000 rads) prior to coculture, rendering them unable to replicate yet still retaining metabolic competency. MCF10A cells were treated (in the presence of MCL-5 cells) with PhIP (1-100 microM) and harvested at various time-points. Compared to DMSO control, treatment (24 or 48 h) with PhIP resulted in a significant dose-dependent fall in cell number. Cells treated for 48 h then cultured in the absence of PhIP (and MCL-5 cells) for a further 6 days showed a much greater dose-dependent reduction in cell number. Flow cytometric analysis indicated that PhIP treatment (48 h) resulted in a dose-dependent accumulation of cells in the G1 population. Western blotting revealed elevated expression of p53 and the cyclin dependent kinase inhibitor p21WAF1/CIP1 after PhIP treatment. Levels of MDM2, a negative regulator of p53, and the hypophosphorylated form of RB were also elevated, consistent with the triggering of G1 cell cycle checkpoint. These cell cycle effects are critical, as they enable cells to effect genome repair, accept mutation, or eliminate excessively damaged cells.