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Le volume consacre a la personne et a l’œuvre de Mme de Graffigny rassemble vingt articles, groupes en quatre parties. Le premier volet, «Francoise de Graffigny, temoin exceptionnel de son temps», considere l’ecrivaine dans son temps et son milieu. Les etudes y sont basees essentiellement sur la correspondance de Mme de Graffigny. De celle avec Duval, ne subsistent que les lettres adressees a l’ecrivaine; Andre Courbet y observe l’expression des pensees et preoccupations entre deux personnes ...

Ultrasound-guided injections of botulinum neurotoxin in cervical dystonia have a number of theoretical advantages. However, their action has never been compared to that of non-guided injections. The objectives of the study were to compare the outcome of botulinum neurotoxin type A treatment in patients with idiopathic, focal cervical dystonia, according to two methods: inspection and palpation of anatomical landmarks (non-guided group) or ultrasound guidance (ultrasound-guided group).We included consecutive patients in this single-center, prospective, real-life, non-randomized study. The outcomes were evaluated one month after the injections: Cervical Dystonia Impact Profile 58 (main outcome), Toronto Western Spasmodic Torticollis Rating Scale-2 (pain and disability subscores), Toronto Western Spasmodic Torticollis Rating Scale-PSYCH, patient-rated Clinical Global Impression - Improvement and adverse events. We used propensity score methods for statistical analysis; ten predefined confounding factors were used to build the propensity score.Sixty-three patients were included in the non-guided group, and 60 other patients in the ultrasound-guided group. We found no difference in main and secondary outcomes between the two study groups.This is the first direct comparison between ultrasound-guided and non-guided botulinum neurotoxin type A injections in patients with cervical dystonia. We hypothesize that ultrasound guidance made it possible to obtain the same results in the most severe (or the most demanding) patients as in the best responders. Further studies are still needed to assess the impact of botulinum neurotoxin injections into deep cervical muscles.

Apart from myeloma, primary prophylaxis of venous thromboembolism (VTE) in ambulatory cancer patients treated with chemotherapy is underused, despite its proven benefit for pancreatic cancer and to a lesser extent for lung cancer. This prophylaxis has been showed to be effective for myeloma, pancreas but in absolute numbers these cancers lead to a few venous thromboembolic events. Up to date, VTE risk scores cannot be used as a discriminatory criterion to select a high-risk population that could really benefit from this prevention. VTE depends in part on oncogenic mutations of tumor cells that result in an imbalance between activation and inhibition pathways that are involved in venous thrombus formation. So, stratification of risk of VTE in cancer patients could be considered from a clinical and molecular point of view and result in a tailored prophylaxis. This "personalized medicine" that is currently used for the anti-tumor treatment of many cancers and hematological malignancies, could lead to a more effective prophylaxis of VTE in cancer patients.

Resume Nous rapportons le cas d’une patiente de 34 ans qui a presente des myoclonies febriles avec une hypertonie spastique irreductible aux membres inferieurs. L’evolution s’est faite vers un coma hyperthermique associe a une defaillance multiviscerale. La presentation clinique etait evocatrice d’une encephalomyelite progressive avec rigidite et myoclonies (PERM) compliquee d’un coup de chaleur. Malgre un refroidissement, la patiente presenta des sequelles cerebelleuses. L’etiologie du PERM reste inconnue. Le coup de chaleur (ou heat stroke en anglais) est une complication redoutable de l’hyperthermie. Il doit etre evoque devant toute dysfonction neurologique dans un contexte d’hyperthermie superieure a 40 °C. L’evolution naturelle se fait vers une defaillance multiviscerale dans un contexte pro-inflammatoire. La mortalite depasse les 40 % et les sequelles neurologiques, principalement cerebelleuses, sont responsables d’un handicap majeur.

Objectif Decrire les intoxications graves associees au mesusage recreatif de protoxyde d’azote rapportees aux centres de vigilance des Hauts-de-France. Historique des cas Depuis la fin 2018 de nombreux cas d’abus de protoxyde d’azote sont rapportes dans la region des Hauts-de-France, parmi lesquels de nombreux cas graves d’intoxication [1] . Methodes Collecte des intoxications graves associees a l’usage recreatif de protoxyde d’azote, rapportees aux centres de vigilance des Hauts-de-France (centres d’addictovigilance, de pharmacovigilance et centre antipoison) du 01 janvier au 31 octobre 2019. Resultats Quinze cas ont ete rapportes, dont 14 dans le Nord (1 dans la Somme), chez 5 femmes et 10 hommes, âges de 18 a 34 ans. Il existait une neuro-toxicite dans les 15 cas (5 scleroses combinees de la moelle, 12 atteintes neurologiques peripheriques dont 2 atteintes mixtes), une toxicite neuro-psychiatrique suspectee (psychose, desorientation spatiale) et cardio-respiratoire suspectee (embolie pulmonaire) dans 2 cas. Les cas d’atteinte neurologique etaient associes a des consommations regulieres, prolongees ou massives, dans 10 cas. Dans un cas de consommation legere et intermittente, les paresthesies ont dure 6 jours, resolutives a l’arret des consommations. Dans 2 cas les paresthesies sont survenues apres une premiere prise en charge medicale pour une atteinte non neurologique (neuro-psychiatrique et cardio-respiratoire). Dans un cas il existait une pharmacodependance authentifiee addictologiquement, avec des consommations prolongees et massives. Discussion La principale toxicite detectee est neurologique, cependant dans deux cas elle etait neuropsychiatrique ou cardiorespiratoire. Si elle est le plus frequemment associee a des consommations regulieres et/ou prolongees et/ou massives, elle peut survenir meme pour des consommations plus legeres ou intermittentes. Une fois reperee le consommateur doit beneficier d’une information claire concernant les risques de complications et une prise en charge therapeutique adaptee, aux risques de voir se constituer une neuro-toxicite grave ou avec sequelles. Les consommations doivent etre evaluees au plan addictologique afin de correctement prendre en charge une eventuelle pharmacodependance, risquant de perenniser une consommation devenant alors reguliere et/ou prolongee, facteur de risque de developper une atteinte neurologique grave. Conclusion Le mesusage recreatif de protoxyde d’azote est a l’origine de complications graves, notamment neurologiques, quels que soient les niveaux de consommations. En cas de non reperage, d’information ou de prise en charge, ce mesusage peut entrainer des complications graves ou des sequelles.

Resume La maladie de Huntington reste une maladie devastatrice pour les patients et leurs familles. Nous aborderons dans cette mise au point tous les aspects utiles pour optimiser sa prise en charge : son diagnostic, ses evaluations et traitements, les aides variees a envisager, enfin quelques notions sur les traitements au stade des essais cliniques.

Idiopathic hypertrophic cranial pachymeningitis (IHCP) is a rare clinical entity, characterized by a chronic inflammation causing thickening of the dura. Adequate therapeutic management is still a matter of debate. We present a patient with an IHCP, non-responsive to corticotherapy. Oral methotrexate was introduced (12.5 mg weekly) and total remission was observed after 6 weeks, both clinically and after neuro-imaging. We conclude that methotrexate can be effective and a therapeutical option in patients with IHCP who are resistant to corticotherapy or present major side-effects of chronic corticosteroids use.

Alcohol-induced hypoglycemia has rarely been studied since it was first described in 1941. Recently some studies have tried to evaluate the prevalence of hypoglycemia truly related to ethanol intoxication. Objectives: We tried to estimate the prevalence of hypoglycemia in a hospitalized alcohol-intoxicated population, and then to compare them to a non alcohol-intoxicated population. Methods: Six thousand one hundred and forty-five patients in whom blood glucose concentration and alcoholemia were measured simultaneously were enrolled in a 4-year retrospective study. Patients with undetectable alcohol levels were considered as the “control” group. Mild to moderate hypoglycemia and severe hypoglycemia were defined as blood glucose levels below 3.72 mmol/L (67 mg/dL) and 2.78 mmol/L (50 mg/dL), respectively. Diabetic patients with possible treatment-induced hypoglycemia were excluded. Results: Fifty-six percent of patient had measurble alcohol levels. The prevalence of mild to moderate hypoglycemia and severe hypoglycemia was 0.76 percent and 0.15 percent, respectively. There was no significant difference between the two groups, even after excluding patients with misleading factors. Conclusions: These results call into question the clinical existence of ethanol-induced hypoglycemia. The rarity of such occurrence put into doubt the relationship between alcohol intoxication and so-called alcohol-induced hypoglycemia. We emphasize the importance of ruling out other causes of hypoglycemia before relating them to alcohol intoxication. We summarize the lack of standardized management protocols for a possible theoretic risk of hypoglycemia associated with alcohol intoxication.

Sir, Since the beginning of the 1990s, 26 members of the CTX-M family have been identified.1 These extended-spectrum β-lactamases (ESBLs) belong to the class A family and most of them have a good hydrolysis for cefotaxime, whereas ceftazidime is a poor substrate. The geographical origin of these enzymes has been much debated recently: South America or Europe?2 For the scientific community, complete characterization of the enzymes is most important (sequence and biochemical properties). The producing strains have been isolated from various areas, but mainly Asia, South America, Africa and Europe.3–6 In February 2001 a multiresistant strain of Escherichia coli (EC 1) was isolated in a urine sample of a 49-year-old French woman (patient 1) hospitalized from 15 January to 17 February in the traumatology unit of our University Hospital (Dijon, France). The patient was hospitalized following spinal trauma. She had not been abroad for 5 years. The strain had a high level of resistance to all broad-spectrum cephalosporins, and a double-disc synergy test was positive. The pI of the ESBL, determined by analytical isoelectric focusing, was 8.6, an unusual value. In May 2001, the Mâcon Hospital Laboratory (100 km from Dijon) sent us an ESBL-producing strain of E. coli, isolated from the wound of an open leg fracture of a 36-year-old French woman (patient 2). In January 2001, the patient went to India on honeymoon, where she was in a car accident. She was first hospitalized in an intensive care unit in New Delhi; 2 weeks later she was back in France. After a 10-day stay in the traumatology unit of our hospital (12–22 January), she was transferred to Mâcon, where she lives. The main trauma affected one leg, with multiple fractures associated with substance loss. The bacterial cultures of urine, and a biopsy of bone, were negative in Dijon. After the transfer to Mâcon, the doctors noticed a wide surface of tissue necrosis, with absence of wound closure, and clinical signs of infection. An ESBLproducing strain of E. coli (EC 2) was isolated in this wound and sent to us for characterization of the enzyme. The EC 2 antibiogram was very similar to that of EC 1, and EC 2 also produced an ESBL with pI 8.6. A comparison, by pulsed-field gel electrophoresis, was performed after digestion of total DNA by XbaI, and revealed that both strains had identical profiles. MICs of β-lactams, determined by a microdilution method, showed that the strains were highly resistant to penicillins (ticarcillin > 2048 mg/L) and broad-spectrum cephalosporins (cefotaxime 1024 mg/L and ceftazidime 64 mg/L). The best inhibition was obtained with clavulanic acid. The strains were also resistant to kanamycin, tobramycin, gentamicin, tetracycline, co-trimoxazole and quinolones. Imipenem and amikacin maintained good activity. Attempts to transfer the ESBL phenotype to E. coli K12-C600 (resistant to sodium azide) or Klebsiella pneumoniae 10031 (resistant to rifampicin) failed. PCR amplifications were negative for blaTEM and blaSHV, but positive with primers specific for blaCTX-M: P1C (5′-TCGTCTCTTCCAGA-3′) and P2C (5′-CAGCTTATTCATCGC-3′), P3C (5′-GCGATGAATAAGCTG-3′) and Fin (5′-CCGTTTCCGCTATTA-3′). The entire coding region of the gene was amplified. Both strands of the PCR products were sequenced. Analysis of the sequences revealed that the ESBL produced by the clinical strains EC 1 and EC 2 was identical to CTX-M15.7 This enzyme differs from CTX-M3 by an aspartic acid to glycine substitution at position 240. The same substitution is also encountered in CTX-M16,8 an enzyme that also provides resistance to ceftazidime in the organisms in which it resides. CTX-M15 was first isolated in Japan. The sequence was submitted in November 2000 by Muratami (Genbank accession number AY013478) but not published. In 2001, the same enzyme was characterized by Karim et al.7 in clinical strains of E. coli, and also in Enterobacter aerogenes and K. pneumoniae isolated in New Delhi. Strains expressing the common CTX-M-type β-lactamases are easily detected: they are resistant to cefotaxime, whereas the activity of ceftazidime is conserved. In the strains EC 1 and EC 2 all broad-spectrum cephalosporins had high MICs: before the determination of the pI there was no suspicion of CTX-M production. Advance Access published January 6, 2003

Resume Cette etude fournit des donnees epidemiologiques concernant l'ensemble des Salmonella isolees au Centre hospitalier general de Mâcon (71) au cours des 10 dernieres annees (1980–1990). Ces donnees sont comparees a celles fournies par l'Institut Pasteur de Paris (Centre national de reference pour les Salmonella et Shigella). Deux cent quarante trois Salmonella ont ete isolees, avec une moyenne de 24 souches par an dont 86 % dans des selles. Elles representent 1 a 2 % des souches identifiees dans les quelques 900 coprocultures annuelles. Les Salmonella se repartissent en 38 serotypes dont les 5 principaux representent 78 % des souches. S. typhi-murium correspond a 49 % de l'ensemble des Salmonella. Il est a noter une grande stabilite de la frequence d'isolement des differents serotypes sur les dix ans malgre deux pics en 1981 et 1987. Celui de 1981 (38 souches) est lie a une epidemie saisonniere de S. panama et a une epidemie hospitaliere de S. bovismorbificans. Le pic de 1987 est essentiellement du a une recrudescence de S. typhi-murium, parallele a celle notee dans l'environnement et dans l'alimentation a l'echelle nationale.

Introduction Les soins pharmaceutiques pendant l’hospitalisation permettent la prevention et la resolution des problemes relies a la pharmacotherapie (PRP). Leur interet n’est plus a demontrer. Neanmoins, leur continuite a la sortie reste un champ d’investigation possible. Il nous a semble indispensable de securiser le lien hopital/ ville, periode de transition a risque de PRP par la mise en place d’un courrier pharmaceutique de sortie. Materiels et methodes Etude prospective observationnelle monocentrique, realisee dans l’unite d’hospitalisation conventionnelle du service d’Endocrinologie au Centre Hospitalier Lyon Sud, Hospices Civils de Lyon. Les patients diabetiques de type 2 hospitalises pour un desequilibre hyperglycemique chronique pendant la periode de l’etude (Juin-Juillet 2012) ont ete inclus. Un courrier pharmaceutique de sortie, a destination du pharmacien d’officine, du reseau d’education therapeutique et du medecin traitant, a ete constitue a partir de l’observation pharmaceutique (entretien d’entree, evaluation des connaissances medicamenteuses, de l’observance, …) et des soins pharmaceutiques dispenses (bilan de conciliation, synthese des modifications therapeutiques, resolution des PRB et courrier pharmaceutique). Un questionnaire de satisfaction des professionnels de sante a ete elabore. Resultats 30 patients ont ete inclus (âge moyen : 60,5 ± 9,9 ans ; Anciennete mediane du diabete 12 ans [9–20] ; HbA1c moyenne : 10,3 ± 2,2 %). 40 % des patients possedent peu de connaissances sur leurs traitements/maladie, 57 % presentent des problemes d’observance, 70 % pratiquent l’automedication, 52 % ne connaissent pas l’HbA1c. 66 % ont adheres au reseau d’education therapeutique. 36 % des prescriptions ont beneficie d’au moins une intervention pharmaceutique. La totalite des professionnels de sante du secteur ambulatoire considerent les informations transmises pertinentes pour assurer la continuite des soins pharmaceutiques et 42 % les ont renseignes dans leur dossier patient. Conclusion La continuite des soins pharmaceutiques est indispensable pour securiser le lien hopital/ville et renforcer la collaboration pharmacien clinicien et professionnels de sante du secteur ambulatoire. Des etudes de plus grandes envergures sont necessaires pour confirmer ces resultats.

The aim of the present work was to investigate the preparation of low molecular weight heparin (LMWH) nanoparticles (NP) as potential oral heparin carriers. The NP were formulated using an ultrasound probe by water-in-oil-in-water (w/o/w) emulsification and solvent evaporation with two biodegradable polymers [poly-epsilon-caprolactone, PCL and poly(D,L-lactic-co-glycolic acid) 50/50, PLGA] and two non-biodegradable positively charged polymers (Eudragit RS and RL) used alone or in combination. The mean diameter of LMWH-loaded NP ranged from 240 to 490 nm and was dependent on the reduced viscosity of the polymeric organic solution. The surface potential of LMWH NP prepared with Eudragit polymers used alone or blended with PCL and PLGA was changed dramatically from strong positive values obtained with unloaded NP to negative values. The highest encapsulation efficiencies were observed when Eudragit polymers took part in the composition of the polymeric matrix, compared with PCL and PLGA NP exhibiting low LMWH entrapment. The in vitro LMWH release in phosphate buffer from all formulations ranged from 10 to 25% and was more important (two- to threefold) when esterase was added into the dissolution medium. The in vitro biological activity of released LMWH, determined by the anti-factor Xa activity with a chromogenic substrate, was preserved after the encapsulation process, making these NP good candidates for oral administration.

Rationnel Le tres grand benefice des deux traitements pivots dans la Maladie de Parkinson (MP) que sont la L-dopa et la stimulation subthalamique sont mis en peril a long terme par l’apparition de troubles axiaux avec des freezing de la marche (FOG). Ceux-ci pourraient etre en partie lies a une depletion dopaminergique et noradrenergique dans les boucles striato-frontales. Le methylphenidate (MPD) pourrait augmenter le niveau dopaminergique et noradrenergique synaptique striatal par inhibition des transporteurs pre synaptique. Objectif Nous avons etudie si le MPD ameliorait les FOG et les capacites attentionnelles chez les patients non dements au stade avance de la MP. Methode Dans cette etude randomisee en double aveugle versus placebo (ClinicalTrials.gov : NCT00914095), les patients, de 13 centres en France, qui avaient des troubles axiaux severes avec des FOG, en depit d’un controle optimal des fluctuations motrices par dopatherapie et stimulation subthalamique, etaient eligibles pour l’inclusion. Les patients etaient assignes au groupe MPD (1 mg/kg/j) ou placebo pendant 3 mois. Le critere primaire etait le nombre de pas au Stand Walk Sit Test (SWS) dans des conditions standardisees sans L-dopa entre la premiere et la derniere visite. Resultats Quatre vingt patients ont ete screenes et 69 patients eligibles ont termine l’etude. Par rapport au groupe placebo, on notait sous MPD une diminution significative du nombre de pas et du temps (au SWS), du nombre de freezing (au FOG trajectory) et du score de handicap moteur (UPDRS III) sans L-dopa associee a une diminution du nombre de freezing apres test au L-dopa. L’attention et la somnolence etaient egalement ameliorees sous MPD. Il n’y avait pas d’aggravation significative des dyskinesies, ni de l’humeur ou de comportement addictif. Une inhibition des transporteurs pre synaptiques de dopamine etait observee sur le DaTSCAN™. Conclusions Le MPD ameliore le freezing de la marche avec un impact positif sur la cognition et le comportement dans une population selectionnee de patients parkinsoniens evolues sous stimulation subthalamique avec des doses moderees quotidiennes de L-dopa.

The fat content and the fat globule size distribution of human preterm milk samples were analyzed and compared with data of previously analyzed samples of term milk. A negative correlation was found between the fat content and the gestational age. In both term and preterm milk three subpopulations of fat globules could be observed. The subpopulations of small (1 to 15 microns) and large globules (8 to 13 microns) were larger in preterm milk, but decreased slower throughout lactation. The average diameter was identical in both milks and increased with advancing lactation. The fat surface, which also depends on the fat content, increased with decreasing gestational age. However, no correlation between the specific fat surface area and the gestational age was found. Compared to human milk, commercial infant formulas have a smaller average fat globule diameter and a larger specific fat surface area.

Continuous search for antineutron annihilation events in an antiproton stack leads to the discovery of a star of 10+15\(\mathop n\limits^{\_\_} \). Of the fifteen shower particles of this star, twelve are identified as electrons and three as pions. A negative pion among the three comes to rest. The ten heavy prongs contain only evaporation protons. All the protons come to rest in the emulsion and each proton has a kinetic energy less than 15 MeV. Dividing the twelve electrons into three groups and assuming each group as the decay of π0→e++e−+e++e−, we can evaluate the masses of the three π0’s respectively as (136±14), (135±14) and (136±13) MeV. The probability for the simultaneous decay of three ordinary π0’s is only 4·10−14. This event suggests the possibility of a new process for the production of electrons,e.g. the existence of a second π0. Considering the high multiplicity, the wide angular distribution and the right average energy of the pions as well as the total energy of the star, we conclude that this event is the result of an annihilation between an antineutron and a nucleon. A small-cell technique is proposed for the measurement of the multiple scattering of the inclined minimum-ionizing tracks.

The study of antineutron annihilation electron showers in K-5 emulsion exposed to 740-Mev/c antiprotons and the conclusion that there is possible existence of a second neutral pion are discussed. (R.E.U.)

In the scanning of antiproton tracks, five antineutron events were found. A reproduction of one of the events is given. The star had 17 prongs involving an associated production of K/sup -/ - K/sup 0/ mesons, with the K/sup 0/ decaying as theta /sup into two pi /sup 0'/s immediately after production and each pi /sup 0/ in turn decaying into a Dalitz pair and a gamma ray. The two electron pairs formed four of the tracks, the K/sup -/ meson formed another, and three knock-on protons, a low-energy electron, an alpha particle, and eight evaporation protons formed the remaining tracks. (M.C.G.)