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Reportar los resultados de la ciclofotocoagulación transescleral con láser micropulsado en una población latinoamericana con glaucoma refractario en un entorno del «mundo real» y evaluar los factores asociados con éxito a un año de seguimiento.

Le bassin industriel de Lacq (Pyrénées-Atlantiques) rassemble depuis soixante ans de nombreuses activités chimiques et pétrochimiques. Afin d’évaluer leur impact sanitaire sur les populations riveraines, Santé publique France a mené un faisceau d’études, dont une écologique sur la mortalité dont l'objectif était d’évaluer une éventuelle surmortalité.

Les bassins industriels constituent des zones cumulant pollutions et nuisances environnementales. Leur impact sur la santé fait légitimement l'objet de préoccupations de la part des riverains. Dans son programme sur le développement durable à l'horizon 2030, l'Organisation mondiale de la santé insiste d'ailleurs sur la nécessité d’étudier l'impact de la présence de sites industriels actuels ou passés sur la santé des riverains et potentiellement source d'inégalités environnementales et sociales de santé. Dans ce contexte, Santé publique France définit, de manière originale, le protocole d'une étude multicentrique nationale de type écologique autour de groupes de bassins industriels présentant des caractéristiques communes en termes d'exposition des riverains.

Le bassin industriel de Lacq (France) rassemble depuis 60 ans de nombreuses activités chimiques et pétrochimiques. Afin d’évaluer leur impact sanitaire sur les populations riveraines, Santé publique France a mené une réflexion sur les indicateurs sanitaires d'intérêt disponibles pour mener une étude écologique de morbidité à une échelle géographique fine sur cette zone.

La question des effets des pesticides sur la santé est devenue ces dernières années une priorité en santé publique et particulièrement en Nouvelle-Aquitaine, première région agricole de France et d’Europe. En 2014, un dispositif pilote de suivi et de gestion des signalements sanitaires liés aux épandages de pesticides a été mis en place afin de :

OBJECTIVE: Connective tissue activating protein-III (CTAP-III), with molecular weight 9278 Da and isoforms including CTAP-III des 1-15 (neutrophil activating peptide-2, NAP-2) and other amino terminal deletion isoforms, has been isolated from human platelets and characterized. Platelets have also been shown to possess significant heparin/heparanase activity. We investigated whether human platelet heparin/heparanase activity derives from CTAP-III. METHODS: Radial immunodiffusion measurement showed substantial amounts of CTAP-III in plasma from outdated platelet packs. A convenient method for measurement of heparin/heparanase activity is described, and with this method platelet associated plasma was investigated for heparin/heparanase activity assayed against 3H-heparin and 35S-heparan sulfate. RESULTS: Removal of CTAP-III from platelet associated plasma with an immunospecific immunoaffinity column did not remove the heparin/heparanase activity from the plasma. Highly purified CTAP-III eluted from an immunospecific affinity column lacked heparin/heparanase activity. CONCLUSION: Human platelet heparin/heparanase activity resides not in CTAP-III but in a protein or proteins with molecular weight ≥ 55 kDa.

Neutrophil attractant/activation protein‐1 (NAP‐1) has sequence similarity to platelet factor‐4 (PF‐4) and to NAP‐2 (a truncated form of connective tissue activating protein‐Ill [CTAP‐III(des 1–15)]. We compared chemotactic activity for neutrophils of these related proteins. We also included for comparison CTAP‐III, CTAP‐III(des 1–13), the C‐terminal dodecapeptide of PF‐4 [PF‐4(59–70)], and C5a. Chemotactic potency (EC50) was highest for NAP‐1 and C5a. Although chemotactic efficacy (peak percentage of neutrophils migrating) was comparable for C5a, NAP‐1, and NAP‐2, the NAP‐2 response occurred only at concentrations 100‐fold higher than the NAP‐1 EC50of 10‐8M. Data for the CTAP‐III proteins confirmed that CTAP‐III is not an attractant and that chemotactic activity appears as a result of cleavage of residues at the N‐terminus to make CTAP‐III(des 1–13) or NAP‐2 [CTAP‐III(des 1–15)]. Chemotactic activity of PF‐4 was low and variable, with no significant response by neutrophils from six of nine subjects. In contrast, PF‐4(59–70) regularly induced high chemotactic responses, although the EC50of 1.6 × 10‐5M was 1,000‐fold greater than that of NAP‐1. The binding of fluoresceinated NAP‐1 to neutrophils was inhibited by unlabeled NAP‐1 or NAP‐2 but not by PF‐4 or PF‐4 (59–70). This suggests that NAP‐2 interacts with the neutrophil NAP‐1 receptor. Despite the low chemotactic potency of NAP‐2, it is a potential attractant at sites of injury because of the relatively large amounts of the parent CTAP‐III released from platelets, as indicated by a serum concentration of approximately 10‐6M.

When antisera to RA synovial fibroblasts were reacted with synovial fluids in immunoelectrophoretic analyses, 90% of RA fluids gave a wing or extended precipi-tin arc pattern. In contrast, 38% of non-RA fluids gave the same types of patterns. The characteristics of the antigen are different from other previously reported synovial fluid components or antigens, and the antigen appears to be a glycoprotein.This study was supported by Grants AM-16326 and AM-10728 from the National Institutes of Health, by a grant from the Illinois Chapter of the Arthritis Foundation, a Clinical Research Center Grant from the Arthritis Foundation, and by Allied Health Professions Advanced Traineeship Grant No. 1-A02-AH00428-01. B. Anderson is the recipient of Research Career Development Award No. AM-70787 from NIH.

Antisera were prepared to the platelet-derived connective tissue activating peptide (CTAP-III) and used to ascertain the presence of CTAP-III materials in a number of biologic specimens by double immunodiffusion analyses. Materials reactive with anti-CTAP-III sera were found in all human sera and platelet extracts tested; weak reactivities were obtained in human plasma specimens but no reactivity was seen in plasma samples for which care was taken to avoid platelet activation. Extracts of synovial fluids and tissues and a spleen extract, processed in the manner similar to the CTAP-III purification scheme from platelet extracts, exhibited positive reactivities. However, synovial fluids contained no detectable reactivity by the double immunodiffusion method. The anti-CTAP-III sera were not reactive with the many polypeptide hormones and growth factors tested, including the CTAP-I and -II factors and platelet factor-4. Previous studies had shown that CTAP-III, β-thromboglobulin, and the low affinity platelet factor-4 share similar or identical antigenic determinatants. CTAP-III has mitogenic activity for many strains of human connective tissue derived cells and the presence of CTAP-III reactive components in synovial tissues suggests that CTAP-III may in part contribute to the proliferative response of those tissues during inflammation.

We investigated the ability of CA III, isolated from adult human skeletal muscle, to regulate cell growth and glycosaminoglycan (GAG) formation in connective tissue cells derived from various human tissues. Unlike muscle, dermal, and cartilage fibroblasts, synovial connective tissue cells were substantially activated by CA III and showed enhanced hyaluronic acid (HA) synthesis. Cell culture experiments showed that CA III induced a 2- to 11-fold increase in [14C]HA synthesis by human synovial fibroblasts (SF) in a dose-dependent manner (P< 0.001); erythrocyte CA I and CA II were inactive. Exposure of SF and muscle fibroblasts to CA III also resulted in a 20-45% and 16–70% increased 35S incorporation into proteoglycans, respectively. When adult human skin and cartilage fibroblasts were studied in the presence of CA III, no differences in the level of DNA and GAG formation were noted. These latter cell types were clearly activated by a platelet (CTAP-III) growth factor. The potential physiological implications of these observations are discussed.

DNA synthesis in guinea pig lung fibroblast cultures was shown to be stimulated by endotoxins, PGE2, CTAP-III, CTAP-P2, and insulin; indomethacin and cortisol partially reversed some of these effects. DNA synthesis in human lung fibroblasts was also markedly stimulated by CTAP-III, while the response to endotoxins was less striking.

Summary: The quantitative radiochemical methodology described in this report allows a major increase in information generation, increased experimental flexibility, improved statistical control, and increased diversity of information per culture. Other advantages relate to economies of technical time, supplies, cells, and test materials per individual culture. Microcultures of human synovial cells incorporate [14C]glucosamine into hyaluronic acid that accumulated primarily in the media and to a lesser extent in the cell mass. CTAP-I (from lymphoid cells), CTAP-III (from human platelets), PGE2, dibutyryl cAMP, and poly(I)poly(C) markedly stimulated hyaluronate synthesis, whereas cortisol, cycloheximide, and tunicamycin inhibited stimulated synthesis. Time studies with cycloheximide indicated that translation, essential for the activation of synovial cells, was completed by 17 h postexposure to CTAP-I. Tunicamycin also seemed to inhibit CTAP-I induced activation primarily by interpering with translation; however, tunicamycin also caused modest post-translational inhibition of hyaluronate synthesis in activated adult human synovial cells.

Summary: Earlier studies showed that guinea pig lung fibroblasts in cell culture could be “activated” by naturally occurring peptides with a resultant increase in glycolysis and glycosaminoglycan formation. Such connective tissue activation (CTA) in human cell systems (synovial, cartilage, dermal) has proved a useful tool for studying the mechanisms of inflammation and dissecting the efficacy and actions of anti-inflammatory drugs. The present study examined the consequences of treating basal and activated guinea pig lung fibroblasts with glucocorticoids. The data indicate that glucocorticoids minimally suppress glycosaminoglycan (GAG) synthesis in nonactivated cultures. Further, CTA was inhibited to only a minor degree in activated lung fibroblast cultures by steroids, and even markedly supraphysiologic concentrations of glucocorticoids were not notably inhibitory. It was of interest that thiols enhanced suppression of incremental GAG synthesis by some glucocorticoids in activated lung fibroblast cultures.

Connective tissue activating peptides (CTAPs) extracted from leukocytes and platelets stimulate glycolysis and synthesis of glycosaminoglycan and DNA in cultured human connective tissue cells. CTAP-III, isolated from fresh or outdated human platelets, is a low molecular weight single-chain protein with an isoelectric point of 8.5 that markedly stimulates DNA synthesis and multiple aspects of glycosaminoglycan and proteoglycan metabolism. This report presents a definitive comparison of CTAP-III prepared by two methods [one designated (A), alternative] with similar platelet proteins described by others, beta-thromboglobulin (beta-TG) and low-affinity platelet factor 4 (LA-PF-4). CTAP-III, CTAP-III(A), LA-PF-4, and beta-TG have common antigenic determinants documented by immunoprecipitation and radioimmunoassay. CTAP-III, CTAP-III(A), and LA-PF-4 are biologically active in that they stimulate DNA and glycosaminoglycan synthesis by human synovial cells; beta-TG is inactive. Carboxyl-terminal digestion gave identical terminal sequences for CTAP-III, CTAP-III(A), and beta-TG. Amino-terminal sequence data indicate that CTAP-III and CTAP-III(A) (also LA-PF-4) are identical and differ from beta-TG only by an additional amino-terminal tetrapeptide (Asn-Leu-Ala-Lys-). The biologically active molecule, CTAP-III, may be proteolytically converted to its inactive degradation product (beta-TG) in the course of platelet aging, platelet storage, release from the platelets, or initiation of biological activity.

Summary: Most glycosaminoglycans (GAGs) formed by lung fibroblasts under both basal and stimulated conditions were secreted into the culture medium. High molecular weight (>106 daltons) hyaluronic acid (HA) was the major GAG species formed. Most of the SO4-GAG synthesized by lung fibroblasts was of proteoglycan (PG) monomer size. Agents stimulating complex carbohydrate formation also exhibited some selectivity with respect to whether HA or PG was formed in incremental amounts. Hyaluronate synthesis was especially stimulated by endotoxins, SO4-GAG by β-xylosides, and PG by CTAP-III.

Connective tissue activating peptide (CTAP-III) is one of the growth factors found in the α granules of human platelets. This small cationic platelet protein shows several apparent isoelectric point variants after the preparative isoelectric focusing step in large scale preparations from multiple donors. Analytical isoelectricfocusing techniques under denaturing conditions, coupled with Western blotting and immunodetection, now show that CTAP-III prepared rapidly from single donors also has multiple isoelectric point variants, suggesting that this finding is more likely related to post-translational modification than preparative artifact or genetic polymorphism.

Primary cultures of fibroblast-like cells from rheumatoid synovial tissue changed in vitroto a cell population exhibiting epithelial morphology, heteroploidy, altered growth characteristics, and decreased capacity to synthesize hyaluronic acid. Quantitative changes in the protein and nucleic acid composition of the cells were also demonstrated.

Administration of ACTH caused chromatolysis in the cells of the paraventricular hypothalamic nucleus. Cortisone affected this nucleus but induced more widespread chromatolysis and vacuolation of thalamic and hypothalamic nerve cells.

Lipids from connective tissue cells cultivated in vitrowere identified by silicic acid column and paper chromatography, and by Dawson's hydrolysis procedures. Phospholipids constituted 64–84% of the total lipid with the remainder approximately equally distributed between cholesterol and the glycerides. Total lipid concentration ranged from 9.1 to 17.2 mg per 100 mg of dry cell solids. Phosphatidyl choline,-ethanol-amine,-myoinositol, sphingomyelin, and plasmalogens were identified in all cells examined. Phosphatidyl serine was undetected in one, and “phosphatidic acid” undetected in several of the cell lines. No unusual intracellular concentration of lipid or definite correlation with mucopolysaccharide production was demonstrated.

The technique of biopsy occupies a position of undisputed importance as a diagnostic procedure. It has not found wide application in the field of rheumatic diseases, however, because of the expense and period of incapacity involved with conventional arthrotomy. The situation was significantly improved, we believe, in 1951, when Polley and Bickel1 described their experiences with an instrument for punch biopsy of the synovial membrane. In several subsequent reports2-4 these authors have confirmed their opinion regarding the diagnostic value of the method. Our initial report 5 was in agreement, stating that the procedure was considered a practical diagnostic method.The Polley-Bickel instrument (Fig. 1) is simply constructed. The main part is a hollow stainless-steel tube with a trocar point and a hooked opening on the dorsal surface near the trocar tip. A hollow tubular knife with a sharp cutting rim fits inside the outer tube and is used

L’impact sanitaire des expositions aux pesticides est une préoccupation de santé publique qui concerne les agriculteurs mais également les populations riveraines. L’objectif du programme Phytosignal est de recueillir des effets de santé attribués aux épandages de pesticides chez des riverains d’exploitations agricoles. Nous présentons ici les résultats préliminaires de ce projet.

L’impact sanitaire des expositions aux pesticides est une préoccupation de santé publique qui concerne les agriculteurs mais également les populations riveraines. L’Objectif du programme Phytosignal® est de recueillir les effets de santé attribués aux épandages de pesticides chez des riverains d’exploitations agricoles. Nous présentons ici les résultats préliminaires de ce projet.

In early 2017, the Regional Unit of Public Health France was solicited for recurring symptoms, mostly irritations and headaches, affecting employees of a 400 people administration office. These symptoms had emerged with the relocation in a new building completely renovated that was characterized by low consumption mode and cumulative new working conditions (open space, reorganization of services). These events led to the evacuation of the building because of non-compliant indoor air analyzes. In order to identify the origin of this episode, surveys were conducted by a multidisciplinary group (epidemiology, occupational health, environment, socio-anthropology) following the recommendations of the National Public Health Agency for the management of unexplained collective syndromes.

Les signalements d’événements de santé inhabituels en milieu professionnel, reçus et traités par l’Institut de veille sanitaire (InVS), sont de plus en plus fréquents. Ils concernent potentiellement plusieurs acteurs locaux et régionaux, et peuvent susciter des réponses retardées, dispersées, parfois incohérentes. Afin de fournir une réponse épidémiologique réactive, adaptée et coordonnée aux signalements et alertes en santé travail, l’InVS déploie depuis 2008 un dispositif régionalisé : les Gast, groupes d’alerte en santé travail. Chaque Gast réunit deux épidémiologistes de l’InVS, l’un de la cellule régionale (département de coordination des alertes et des régions, Dcar) et l’autre du département santé travail (DST), un médecin inspecteur régional du travail de la Direccte et un médecin de la consultation de pathologie professionnelle (CPP) du centre hospitalier universitaire. L’ARS, le médecin du travail, le CHSCT, l’entreprise sont impliqués et régulièrement informés du traitement du signalement. Le dispositif des Gast, qui a vocation à couvrir l’ensemble du territoire national, est à ce jour implanté dans dix régions métropolitaines. Une base de données nationale permet d’enregistrer tous les signalements et les réponses apportées, d’analyser et faire le bilan annuel des activités de veille et d’alerte de l’InVS dans le domaine des risques professionnels. Ce système est étroitement lié aux dispositifs nationaux et régionaux de santé publique et de santé au travail.

The purpose of this study was to determine the prevalence of oral feeding problems at hospital discharge for preterm infants and to assess if these could be markers of later disability. This was a retrospective review of patients enrolled in a follow-up clinic database. Infants included were = 32 wk GA, seen for the initial clinic visit between January 1, 2002 to December 31, 2004. 71/328 (22%) infants had oral feeding disorders (OFD) as defined by having one or more of the following at hospital dismissal: use of tubes and/or feeding pump, feeding more frequently than every 3 hours secondary to poor volume tolerance, and/or less than 100% of feeding orally. A comparison group of infants was determined by matching each study infant with the next infant in the database without a feeding problem but with the same GA (± 1 wk) and BW (± 100g). Medical complications and limited outcome data were obtained by database review. Group differences were determined by chi-square and univariate analysis of variance with significance indicated by P<.05.There were no group differences in BW (1023 ± 370 and 1026 ± 345 g, OFD and control, respectively), GA (27.6 ± 2.5 wk, both), or gender. OFD infants were, on average, discharged from the hospital 5 weeks later and 880 g heavier than comparisons (P=.000). There were no group differences in rates of severe IVH or ROP. OFD infants were more likely to have CLD (52% and 35%, P=.04) and be discharged on a home apnea monitor (47% and 25%, P=.009). 39% of OFD infants had neither CLD or IVH. A subset of infants had 24-month developmental screening using the Bayley Infant Neurodevelopmental Screener (BINS). Controlling for CLD and maternal race, OFD infants (n=14) tended to have a lower mean BINS scores than comparisons (n=30), 6.9 ± 3.6 and 4.3 ± 3.2, P=.08.Preterm infants appear to frequently have oral feeding problems at hospital discharge. Additional study of this population is needed to determine possible etiologies and long-term implications of delayed oral feeding, which could be a unique marker of disability.