Memoir of John Barclay Biddle, M.D.

Memoir of John Barclay Biddle, M.D., Late Professor of Materia Medica and General Therapeutics in The Jefferson Medical College of Philadelphia. Read before the College of Physicians of Philadelphia, June 4, 1879

Photo- and thermal-oxidation of polyethylene : Comparison of mechanisms and influence of unsaturation content

The behaviour of polyethylene with different contents in vinyl and t-vinylene groups have been studied by photooxidation with λ>300 nm light or by thermooxidation at a temperature of 100 °C. The oxidation was studied by infrared spectroscopy and it was shown that the same oxidation products were obtained, but with different relative concentrations depending on the conditions of ageing, i.e. photochemical or thermal conditions. The mechanisms by which the oxidation products are formed were recalled. The differences between photo- and thermo-oxidation were evidenced on the basis of the stability of ketones that do not accumulate in photochemical conditions, as a result of Norrish reactions. The influence of the initial amount of unsaturated groups on the rates of oxidation was characterized. It was shown that the concentration of unsaturations had no effect on the rate of photooxidation but dramatically influenced the stability in thermooxidative conditions

A new biophysical decompression model for estimating the risk of articular bends during and after decompression

International audienceThe biophysical models that intend to predict the risk of decompression sickness after a change of pressure are not numerous. Few approaches focus in particular on joints as target tissues, with the aim to describe properly the mechanisms inducing pain. Nevertheless, for this type of decompression incidents, called , no model proved to fit the empirical results for a broad range of exposures and decompression procedures. We present here an original biophysical decompression model for describing the occurrence of articular bends. A target joint is broken down into two parts that exchange inert gases with the blood by perfusion and with each other by diffusion over distances of a few millimeters. This diffusion pathway allows the slow amplification of microbubbles growing during and after decompression, consistent with the possible delayed occurrence of bends. The diffusion coefficients introduced into this model are larger than those introduced into most modern decompression models. Their value remains physical (#10m/s). Inert gas exchanges and the formation, amplification and resorption of microbubbles during and after decompression were simulated. We used a critical gas volume criterion for predicting the occurrence of bends. A risk database extracted from COMEX experience and other published studies was used for the correlation of model parameters not known . We considered a large range of exposure, and the commonly used inert gases nitrogen and helium. This correlation phase identified the worst biophysical conformations most likely to lead to the formation, in tissues such as tendons, of a large number of microbubbles recruited from pre-existing gas nuclei during decompression. The risk of bends occurrence was found to be linked to the total separated gas volume generated during and after decompression. A clamping phenomenon occurs soon after the start of decompression, greatly slowing the gas exchanges controlled especially by the oxygen window. This model, which reproduces many empirical findings, may be considered both descriptive and predictive

La France des Plantagenêts et l’emblème héraldique du lion dans les pièces historiques de Shakespeare

Dans la saga historique shakespearienne, de King John à Henry VIII, les fiefs plantagenêts, conquis, perdus, reconquis, définitivement abandonnés, demeurent une obsession commune aux souverains anglais en succession. L’emblème héraldique du lion, associé au semis de fleurs de lys, orne le blason des successeurs de Richard Coeur de Lion. Les rites de la chevalerie, en usage au cours des guerres de France, perdurent jusqu’à la démise de Richard II, qui scelle le début de l’ère moderne. La guerre fratricide des Deux Roses qui s’ensuit conduit à la perte de l’héritage angevin, en même temps que disparaissent les règles chevaleresques et la signification symbolique du bestiaire héraldique. Par ironie, sur la scène shakespearienne, les rois d’Angleterre continuent de se réclamer du lignage plantagenêt, alors même que l’héritage d’Aliénor d’Aquitaine est perdu à jamais.The Shakespearian historic saga, from King John to Henry VIII, makes of the Plantagenet dominions, whether they are conquered, lost, re-conquered or definitively abandoned, a common obsession amongst the successive English sovereigns. The heraldic emblem of the lion, in connection with the flag scattered with fleurs-de-lys, adorns the coats of arms of Richard Lion Heart’s successors. The rites of chivalry, in use during the wars in France last until Richard II is deposed, which marks the start of the modern age. The fratricide war of the Two Roses which ensues leads to the loss of the Anjou legacy, while at once and the same time, the chivalric code and the symbolic meaning of the heraldic bestiary are also lost. Ironically, on the Shakespearian stage, the English kings continue to claim Plantagenet lineage, at a time when the inheritance from Eleanor of Aquitaine is definitely lost

Etude de l'utilisation des médicaments dans la maladie d'Alzheimer et maladies apparentées

La maladie d'Alzheimer (MA) représente l'étiologie principale de la démence. A l'heure actuelle, les seuls traitements pharmacologiques à disposition sont symptomatiques, il s'agit des médicaments dits "spécifiques " de la démence : inhibiteurs de l'acétylcholinestérase (IAchE) et mémantine. Cependant, leur efficacité reste très discutée et la durée optimale de leur utilisation n'est pas clairement établie. Par ailleurs, l'utilisation des neuroleptiques, en réponse aux troubles des comportements de la démence dits " perturbateurs ", est fréquente, bien que réalisée hors recommandations et pour la plupart hors autorisation de mise sur le marché. Une augmentation du risque de décès sous neuroleptiques a été évoquée, conduisant à la publication d'alertes émises par l'Agence Française de Sécurité Sanitaire des Produits de santé (AFSSaPS) en mars 2004 et décembre 2008. Ce travail était centré sur l'étude pharmaco-épidémiologique des médicaments spécifiques de la MA et des neuroleptiques en population présentant une MA. La première partie de cette thèse avait pour objectif d'identifier les facteurs prédictifs et l'incidence de non persistance (arrêt, changement) des médicaments spécifiques de la démence. Notre premier travail était réalisé parmi 611 sujets atteints de MA, recrutés en centres experts universitaires français (cohorte REAL.fr), utilisateurs prévalents d'IAchE. Il a permis d'estimer l'incidence de l'arrêt et du changement des IAChE à 3,6 (IC95% :[2,3-4,8]) et 9,2[7,0-11,3] pour 100 personne-année, respectivement. Notre second travail était conduit parmi 557 utilisateurs incidents d'IAchE dans une cohorte européenne de patients atteints de MA, recrutés en centres experts (cohorte ICTUS). L'incidence de l'arrêt et du changement des médicaments spécifiques étaient de 9,7[7,4-11,9] et 12,5[9,86-15,11] pour 100 personne-année. Les facteurs prédictifs d'arrêt étaient des marqueurs d'effets indésirables médicamenteux (posologie inefficace, faible indice de masse corporel, chutes), l'existence de troubles psycho-comportementaux, la progression de la MA sur le plan cognitif, la posologie inefficace, une hospitalisation récente, et la spécialité du centre. Les facteurs prédictifs de changement étaient l'ancienneté de la MA, la sévérité de la MA (MMSE<15), la progression de la MA sur le plan fonctionnel, la posologie inefficace, un recours élevé aux aides infirmières et la spécialité du centre. La seconde partie de cette thèse était centrée sur l'utilisation des neuroleptiques. Elle consistait à étudier le risque de mortalité sous neuroleptiques, puis à décrire l'évolution temporelle de l'utilisation des neuroleptiques en France, en étudiant l'impact des alertes émises par l'AFSSaPs. Notre troisième travail, réalisé dans la cohorte REAL.fr, mettait en évidence que, si l'utilisation de neuroleptiques était prédictive d'une surmortalité en analyse univariée et avec un ajustement limité, cette association perdait toute significativité (HR ajusté : 1,12 [0,59-2,12]), en particulier dès ajustement sur des facteurs de confusion tels que la sévérité de la maladie (déclin cognitif). Le quatrième et dernier travail, centré sur l'exposition aux neuroleptiques dans la démence en France, était réalisé dans les données de l'assurance maladie française (échantillon généraliste de bénéficiaires). Si les tendances d'utilisation montraient une diminution régulière de l'exposition aux neuroleptiques durant la période 2003-2011 (passant de 14,2% à 10,2%), cette dernière portait majoritairement sur les agents non concernés par la première alerte. La diminution observée n'apparait pas donc liée aux alertes. L'étude du bon usage des médicaments dans la MA reste à poursuivre.The leading cause of dementia is Alzheimer's Disease (AD). To date, the drugs marketed in AD (cholinesterase inhibitors and memantine, also called antidementia drugs) are symptomatic and of limited efficacy. In particular, the optimal treatment duration is still under debate. In addition, neuroleptics (antipsychotics) are commonly used in behavioural and psychological symptoms of dementia (BPSD). However, their use remains mostly off label and an increased mortality risk has been suggested with these agents. This led to 2 warnings in march 2004 and December 2008 issued by the French drug agency (AFSSaPS). Data about longitudinal drug use's patterns among clinically confirmed AD patients in a real-life setting remain scarce. This thesis dealt with pharmacoepidemiologic studies of antidementia drugs and antipsychotics is subjects with Alzheimer's Disease or associated disorders. The first part of this thesis aimed to (i) estimate the incidence of antidementia drugs' discontinuation and switch, and (ii) to identify predictive factors of these 2 outcomes. We conducted 2 researches in 2 cohorts. The first analysis was conducted among 611 French AD patients followed for 2 years. The second analysis was performed among a European cohort of 1375 subjects with AD followed for 2 years. We restricted this analysis to the antidementia drugs new users (n=557). The second part of this thesis aimed to study antipsychotic drug use in AD and associated disorders. We first studied the mortality risk associated with antipsychotic use in a 4-year cohort of 686 French subjects with AD. We secondarily described trends in the use of antipsychotic drugs in France between 2003 and 2011, and assessed the impact of AFSSaPS warnings. To this aim, we conducted an interrupted time series study among subjects with and without dementia in the French main Health Insurance Scheme. Patterns of drug use and proper use of medicinal drugs in AD need to be further investigated

Photooxidation of Polypropylene/Montmorillonite Nanocomposites. 2. Interactions with Antioxidants.

2005 American Chemical SocietyThe influence of stabilizing additives on the photooxidation of polypropylene/montmorillonite (PP/ MMt) nanocomposites exposed to UV light was studied. Two différent stabilizers were used, a phenolic antioxidant and a redox antioxidant. A significant reduction in the induction period of oxidation was observed in the presence of MMt. This is believed to arise from interactions between the additives and the nanoclay. The interactions could involve the adsorption of additives onto the clay, the degradation of the alkylammonium cations exchanged in MMt, and the catalytic effect of iron impurities of the organomontmorillonite. Iron could catalyze the decomposition of the primary hydroperoxides formed by photooxidation of PP, which would in turn accelerate the additive consumption and decrease the length of the period before the permanent regime of oxidation is reached

Effect of n-3 fatty acids on metabolism of apoB100-containing lipoprotein in type 2 diabetic subjects

The effect of long-chain n-3 PUFA on the metabolism of apoB100-containing lipoprotein in diabetic subjects is not fully understood. The objective of the present study was to determine the effect of a daily intake of 1080mg EPA and 720mg DHA for diabetic subjects on the kinetics of apoB100-containing lipoprotein in the fasting state. A kinetic study was undertaken to determine the mechanisms involved in the effects of n-3 fatty acids in terms of a decrease in triacylglycerol level in type 2 diabetic patients. We have studied the effect of fish oils on the metabolism of apoB100 endogenously labelled by [5,5,5-2H3]-leucine in type 2 diabetic patients in the fasting state. The kinetic parameters of apoB100 in VLDL, intermediate-density lipoprotein and LDL were determined by compartmental modelling in five diabetic subjects before and 8 weeks aftern-3 fatty acid treatment. Treatment did not change the plasma cholesterol level (0·801 (sd 0·120)v. 0·793 (sd 0·163) mmol/l) but lowered the plasma triacylglycerol level (1·776 (sd 0·280) v.1·356 (sd 0·595) mmol/l; p<0·05). Treated patients showed a decrease in VLDL apoB100 concentration (0·366 (sd 0·030) v.0·174 (sd 0·036) g/l; v<0·05) related to a decrease in VLDL 1 production (1·49 (sd 0·23) v.0·44 (sd 0·19) mg/kg per h; p<0·05) and an increase in the VLDL conversion rate (0·031 (sd 0·024)v.0·052 (sd 0·040) per h; p<0·05), with no change in fractional catabolic rates. Treatment led to a higher direct production of intermediate-density lipoprotein (0·02 (sd 0·01) v 0·24 (sd 0·12) mg/kg per h; p<0·05). In conclusion, the present study, conducted in the fasting state, showed that supplementation with n-3 fatty acids in type 2 diabetic patients induced beneficial changes in the metabolism of apoB100-containing lipoprotei

In Situ Kinetics Study of the Accelerated Aging of Poly(ethylene oxide) Using PhotoDSC

PhotoDSC has been applied to follow the global kinetics of chain scissions resulting from the UV light irradiation or from the thermal degradation of a high molecular weight PEO (4 106 gâmol-1). Infrared spectroscopy, XRD measurements and rheology experiments were performed to evidence the occurrence of chain scissions. Melting energy was used as a tool to quantify the extent of the degradation. It was found that the chain scissions reaction follows a first-order kinetic law for both photo and thermal degradation. The activation energies were found identical in both cases (41 kJ mol-1), whereas the degradation rate was higher in the case of UV irradiation than in the case of thermoageing