Salpetriere Research Articles

G.P.150: Clinical heterogeneity in adult forms of FHL1 related myopathies. The “Institut de Myologie” experience

FHL1 gene mutations are responsible for reducing body myopathy (RBM), a rare condition characterized by progressive muscle weakness and the presence of intracytoplasmic aggregates. Age at onset ranges from early onset in infancy, through childhood and in some cases adult age. FHL1 mutations may also lead to allelic disorders including Emery-Dreifuss like muscular dystrophy (EDMD), hypertrophic cardiomyopathy (HCM), X-linked myopathy with postural muscle atrophy and generalized hypertrophy (X-MPMA) and X-linked scapuloperoneal myopathy (X-SM). To report clinical, muscle imaging, histological and genetic features found of adult patients carrying FHL1 mutations, we retrospectively reviewed their medical reports of the 11 patients (6 M, 5 F) belonging to 8 families followed at the “Institute de Myologie”, Pitie-Salpetriere hospital, Paris. The 11 patients were assessed from 13 to 52 years old. Pseudodominant mode of inheritance was suggested in 4 families, X-linked in 3 and sporadic in one. Four had EDMD, 2 X-SM, 1 X-MPMA, 1 HCM while 2 patients had atypical features and 1 was still asymptomatic. When symptomatic, female patients had a striking asymmetric muscle involvement. Five patients had hypertrophic cardiomyopathy requiring heart transplantation in one patient at 18 years old. Two patients required night time ventilation due to diaphragm paralysis. Histologically, only 3 patients among the 8 probands had reducing bodies (RBs) at muscle biopsy, while 3 had non specific pattern, 1 had neuropathic pattern and one muscle biopsy was considered as normal. In contrast to infantile forms of FHL1 related myopathy that usually show RBs at muscle biopsy and lead to early death, adult forms had wider clinical and histological presentations. Moreover, FHL1 gene screening should be considered in those undiagnosed patients suffering from myopathies with diaphragm paralysis and/or HCM where X-linked inheritance is not excluded even in the absence of RBs at muscle pathology.

P11.05 * LENALIDOMIDE IN THE TREATMENT OF RELAPSED PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA (PCNSL)

BACKGROUND: Lenalidomide is an immunomodulator agent that exhibits efficacy in multiple myeloma and haematological malignancies including refractory/relapsed diffuse large B-cell (DLBC) systemic lymphoma. METHODS: Retrospective review of PCNSL patients treated with lenalidomide at the Pitie-Salpetriere hospital. Inclusion criteria were: 1) immunocompetent status 2) pathologically proven diagnosis of DLBC-PCNSL, 3) recurrent or refractory disease after at least two prior chemotherapy treatments, including intravenous high-dose methotrexate and cytarabine based regimens, 4) lenalidomide administered orally, at a dose of 25 mg/day on days 1-21 of a 28-days cycle. MRI scans were performed monthly. Response was evaluated according to the IPCG criteria. RESULTS: Between June 2011 and March 2013, 6 patients (4 women and 2 men) met the inclusion criteria. Lenalidomide was given as 3rd line in four patients, as 4th line in one and 5th line in one. Median age was 73.5 years (range 64-78) and median Karnofsky Performance Status was 60 (range 40-70). Two patients achieved complete response (CR). Patient 1 received a total of 9 monthly cycles of lenalidomide without any steroids and is still in remission after a follow-up of 18 months from the start of the treatment. Patient 2 achieved a CR and was off-steroids at the time of CR, but relapsed during the 3rd cycle and died after 14 weeks. Patient 3 achieved a partial response after one cycle but died suddenly during the 2nd cycle. Patients 4, 5 and 6 progressed and died 2, 5 and 6 months respectively after the start of lenalidomide. One of them who suffered from an oculo-cerebral relapse demonstrated a partial ocular response while progressing in the brain. Apart from the sudden death of unknown cause, the treatment was well tolerated. None of the patients experienced any grade III or IV toxicity. CONCLUSIONS: These results suggest that lenalidomide exhibits activity in heavily pre-treated PCNSL and is well tolerated in elderly patients. Lenalidomide efficacy on PCNSL needs to be evaluated prospectively, alone or in association with other cytotoxic agents. A phase II trial combining rituximab and lenalidomide for recurrent PCNSL is on-going in France ({type:clinical-trial,attrs:{text:NCT01956695,term_id:NCT01956695}}NCT01956695).

Une leçon clinique à la Salpetriere, 1887: trois conceptions de la mise en scene theatrale

Our premise is that the method of teaching at the bedside at the Salpetriere hospital – about hysteric disease – at the end of the nineteenth century and all the various conceptions of staging and direction in theatre at the same period partake of the same cultural juncture, characterized by a circulation ‒ transfers through contact, shifts and superpositions ‒ of different experiences in the act of looking. This paper examines three of such experiences, which were particularly common in theatres in Paris at the turn of the twentieth century: the clinical experience of looking, developed by Andre Antoine at the Theâtre-Libre; the haptic experience found in spectacular shows, with the Grand Guignol as one of its prime examples, and the hypnotic experience in the staging of symbolist theatre.

RecurrentBordetella holmesiiBacteremia and Nasal Carriage in a Patient Receiving Rituximab

Recurrent<i>Bordetella holmesii</i>Bacteremia and Nasal Carriage in a Patient Receiving Rituximab

A Hysterical Reading of Rodin'sGates of Hell

This paper offers a new reading of Auguste Rodin's most important sculpture, the Gates of Hell, by arguing that the artist engaged with the visual language of and the wider discourse on hysteria, which permeated not only the French popular and scientific press but also the culture at large in the last decades of the nineteenth century. Recently uncovered archival evidence reveals Rodin's strong ties to the familiy and intellectual circle of Doctor Jean-Martin Charcot of the Hospital de la Salpetriere, affording the sculptor exceptional exposure and access to the medical discourse on hysteria. Rodin assimilated and adapted the lexicon of hysterical postures for the figures that populate the Gates of Hell, using the great malady of the century to suggest the modern human condition and thereby creating a new and potent sculptural idiom that we recognize today as idiosyncratic of Rodin -and distinctly modern.

EPR/alanine dosimetry applied to Leksell gamma knife perfexion

Introduction Specificities of the Leksell Gamma Knife (LGK) forbid using reference conditions recommended by international radiotherapy beam calibration protocols. In this framework, the Laboratoire National Henri Becquerel and the Pitie-Salpetriere Hospital decided to check the beams calibration and the dose delivered (”end-to-end” test) by the LGK Perfexion. Moreover, this study aims to compare delivered dose by the two latest software versions of the Gammaplan Treatment Planning System (TPS). Materials The dosimetric method chosen is the Electron Paramagnetic Resonance (EPR) of alanine combined with Monte Carlo simulations. Dose rate measurements have required the phantom spherical ABS Elekta and for the test ‘‘end-to-end” an anthropomorphic head phantom. Methods EPR measurements associated with Monte Carlo simulations allowed the LNHB to develop a method to compare the results to the dose rates measured by ionization chamber. The ‘‘end-to-end” test was done following the patient circuit: CT-scan processing, Treatment planification with 16 mmand 16 mm+8 mmcollimations. The measured values were compared with those delivered by the TPS. Results An average difference of 0.8% between dose rates measured by alanine and ionization chamber was obtained. For the test ‘‘endto- end”, a mean difference of −1.7% (version 9 TPS) and −0.9% (version 10) were obtained. Conclusion Results show a good agreement between beam calibration and alanine measurements brought back to the TRS 398 reference conditions. Results of ‘‘end-to-end” tests gave a good agreement between measured values calculated. However, this study highlighted the impact of the heterogeneities that are not taken into account for TPS dose calculations.

High Efficiency of ICE (Ifosfamide-Carboplatin-Etoposide) in Relapse/Refractory Primary Central-Nervous System and Intra-Ocular Non Hodgkin Lymphoma, After First Line Treatment Containing High Doses of Methotrexate and Cytarabine. A Monocentric Retrospective Study From 2010 to 2012 On 17 Cases

AbstractAbstract 3664 Background:Primary central nervous system lymphoma (PCNSL) and primary intra-ocular lymphoma (PIOL) are at very high risk of relapse after a first line treatment, and then carry a very poor prognosis. Autologous stem cell transplantation (ASCT) can offer prolonged responses but its results clearly depend on efficiency of salvage chemotherapy (Soussain, haemtologica, 2012). Since recent publications on first line treatment of PCNSL and PIOL recommend high dose methotrexate (Mtx) and cytarabine (AraC) (Ferreri, Lancet 2009), salvage chemotherapy must use other drugs with high level of penetration in the central nervous system (CNS). In this setting, ICE regimen, validated in systemic non Hodgkin lymphoma, seems to be appropriated but no data is published in PCNSL and PIOL. Methods:From june 2010 to may 2012, all relapse/refractory PCNSL and PIOL treated in first line by high doses of Mtx and AraC in the Pitie-Salpetriere Hospital, Paris, France, where treated by ICE regimen : ifosfamide (5g/m2 at day 2), carboplatine (AUC 5 at day 2) and etoposide (100mg/m2/d days 1 to 3). Doses where adapted on patient general status and ASCT proposed when possible. Results:Seventeen patients have been treated, 7 females and 10 males, median age 62 [28–84]. Four where refractory and 13 in relapse, with a mean progression free survival (PFS) of 368 days [85–1763], 4 had a second line, one a third before ICE. At moment of ICE treatment, localizations where 10 CNS, 2 CNS + PIOL, 3 PIOL and 2 meningitis. The mean number of cycles was 4 [1–6] and 4 patients needed a dose reduction. During treatment, grade 3/4 WHO toxicities where: 6 neutropenic fever (one death), 5 anemia, 9 neutropenia, 10 thrombopenia and one CNS complication (coma and hypersalivation). ASCT have been made in 6 patients (5 in CR, 1 in PR) and are pending in 3. Complete response (CR) have been obtained in 13 patients (76%), partial in 2. With a mean follow-up of 405 days, 6/15 patients in response relapsed (only one after ASCT), in a median of 81 days, 9 patients died (7 by progression, one during treatment and one in CR). Median Overall survival (OS) was 220 days for all patients but was not reached in case of ASCT. Conclusion:ICE regimen is very effective in relapse/refractory PCNSL and PIOL heavily treated by high dose Mtx and AraC. This efficacy can allow to perform ASCT in eligible patients, chemosensitivity being the most important factor influencing the OS and PFS after ASCT. ICE can represent a new standard in this setting. Disclosures:Leblond:Roche: Advisory Board Other, Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Mundipharma: Honoraria; Janssen-Cilag: Honoraria.

Specific guidelines on wound and wound‐bed management 2011

Foot Ulcer Trials Unit, Nottingham University Hospitals Trust, Nottingham, UK St George’s Vascular Institute, St George’s Healthcare NHS Trust, London, UK Department of Endocrinology, University Hospital of Malmo, Sweden Southern Arizona Limb Salvage Alliance (SALSA), University of Arizona College of Medicine, Tucson, Arizona IWGDF, Heemstede, The Netherlands Service de diabetologie, Hopital Pitie-Salpetriere, Assistance Publique des Hopitaux de Paris, and Universite P et M Curie, Paris, France Department of Endocrinology, Lund University Hospital and Institution for Clinical Sciences in Lund, Sweden School of Healthcare Studies, Cardiff University, Cardiff, UK

A tribute: Abel Ayerza and pulmonary hypertension

In the history of research on pulmonary hypertension, one of the key landmarks was the clinical description of the disease, which was made in 1901 by Abel Ayerza. From then on, in the international medical literature (especially the French, British and American literature), so-called “Ayerza's disease” encompassed various aetiological forms of pulmonary hypertension, discriminated today thanks to developments in the understanding of this disease and its current classification. Abel Ayerza was born in Buenos Aires, Argentina, in 1861. After achieving a doctorate with a gold medal in 1886 from the School of Medicine at the University of Buenos Aries, he travelled to Paris, France where he specialised with Jean Martin Charcot and Francois Joseph Babinski at the Hopital de la Salpetriere, Pierre Carl Edouard Potain at the Hopital de la Charite and Francois Sigismond Jaccoud at the Hopital de la Pitie. On his return to Argentina, he joined the Hospital de Clinicas at the University of Buenos Aires, where, at the age of 37, he was appointed Professor of the First Chair of Medicine. Figure 1. Portrait of Dr Abel Ayerza (courtesy of the Ayerza family). On August 20, 1901, Dr Ayerza described a patient with a history of chronic cough and sputum, dyspnoea, severe cyanosis, profound daytime sleepiness and manifestations of right heart failure. The patient was a 38-yr-old male who had suffered from pneumonia at 20 and 32 yrs of age and since then had had respiratory symptoms. Dyspnoea was severe at rest and there was central cyanosis, clubbed fingers and tachypnea. In …

Clinical Management of Acute Schistosomiasis: Still Challenging!

Two recent outbreaks of acute schistosomiasis (AS) are described in this issue of the journal.1,2 These cases bring to light the difficulties in the diagnosis and management of AS as it has been recently addressed in the literature.3,4 The diagnosis of AS remains difficult, although molecular tools may be helpful as illustrated during one of the reported outbreaks.1 Clinically, the association of fever, angioedema, dry cough, urticaria and high blood eosinophilia clearly points to an allergic reaction to the migrating and maturing helminth larvae such as in AS.4 Diagnosis during this very early phase of the parasitic lifecycle classically relies on serological testing. The sensitivity and specificity of serological tests for AS diagnosis reach 80 and 97%, respectively when a combination of ELISA and indirect hemagglutination assays are used.5 However, following exposure, the median time to seroconversion is about 46 days, whereas clinical signs appear after about 30 days and ranges can be … Corresponding Author: Stephane Jaureguiberry, MD, Department of Infectious and Tropical Diseases and Parasitology‐Mycology, Hopital Pitie Salpetriere, Assistance Publique des Hopitaux de Paris, University Pierre et Marie Curie, 47‐83 Bvd de l’Hopital, Paris 75013, France. E‐mail: stephane.jaureguiberry{at}psl.aphp.fr

Journal-related Activities and Other Special Activities at the 2011 American Society of Anesthesiologists Annual Meeting

Journal-related Activities and Other Special Activities at the 2011 American Society of Anesthesiologists Annual Meeting

The Salpêtrière Hospital in Paris and Its Role in the Beginnings of Modern Rheumatology

In the early hours of the morning of August 31, 1997, Diana, Princess of Wales, was a passenger in a Mercedes-Benz being driven at high speed through the fashionable 8th Arrondissement of Paris. Passing through a tunnel along the Seine River, the vehicle ran into a wall. An ambulance took her to the decidedly unfashionable 13th Arrondissement, where she was pronounced dead about 2 hours later at La Salpetriere Hospital. La Salpetriere, or saltpeter works (intriguing name for a hospital!), the largest hospital in Paris, has a fascinating history. About 400 years ago, an arsenal for the manufacture of munitions was relocated to the present Salpetriere site from across the river. Since gunpowder is largely a mixture of sulfur and saltpeter (KNO3), the site was referred to as the saltpeter works. This appellation has been applied to the successive institutions that have stood on this site, and persists to this day. Under Louis XIV, who reigned from 1643 to 1715, a large proportion — estimated as high as 10% — of the Paris population of 400,000 were homeless beggars. They were not just underprivileged, they had nothing: no money, no honest way to earn money, nothing to eat, nowhere to live. They were dressed in rags. Of course they had some alternatives: crime, begging, prostitution, and suicide. All these alternatives were employed. Clearly, this situation had the potential for major social disorder. At the same time, the middle of the 17th century saw the rise of concern for the poor, spearheaded by the efforts of St. Vincent de Paul. His influence, combined with the perceived need for greater social stability, prompted the King in 1656 to remove undesirable members of society from the streets by sheltering them in grand settings1. His motivation: “to put an end to …

Elective Impella Recover LP 5.0 utilization for postcardiotomy low-output syndrome after aortic valve replacement

a Division of Cardiac Surgery, Pitie-Salpetriere Hospital, University “Pierre et Marie Curie”, Paris 6, Paris, France b Ph.D. School in Cardiothoracic and Respiratory Science, Cardiovascular Surgery Unit, II University of Naples, Naples, Italy c Ph.D. School in Cardiovascular Science, Cardiovascular Surgery Unit, University of Verona Medical School, Verona, Italy d Department of Anaesthesiology, Pitie-Salpetriere Hospital, University “Pierre et Marie Curie”, Paris 6, Paris, France

A History of Multiple Sclerosis

This volume is part of the Healing Science: Disease, Medicine, and History series edited by John Parascandola. The goal of this series is to present history of medicine to a broad-based general audience, rather than limiting its readership to medical historians and physicians. With the exception of the final chapter, this book fulfills this mission. The author, Colin Talley, is an assistant professor of Behavioral Science and Health Education at Emory University who took his history of medicine training at the prestigious University of California at San Francisco program. The author begins his short text by defining multiple sclerosis as a disease of the spinal cord and brain that strikes adults between 20 and 50 years of age. In 2007 there were between 266,000 and 400,000 cases reported in the United States and over 2.5 million worldwide. He then outlines this book's content by asking a series of questions he intends to answer in his book. Why did multiple sclerosis emerge as a distinct neurological disease at the end of the nineteenth century in France? Talley credits this medical breakthrough to the clinical work conducted by Jean-Martin Charcot at the La Salpetriere hospital in Paris, beginning in the late 1860s. Until then multiple sclerosis had been misdiagnosed as a wide variety of neurological disorders. The author then asks, why did multiple sclerosis go from being a little diagnosed disease in the first half of the twentieth century in the United States to becoming a major neurological disorder by the late 1940s? He credits this major change to the rise of the neurology specialty and the impact of lay activities lead by the National Multiple Sclerosis Society, which started its work in 1946.

MEG Detects Alpha-Power Modulations in Pulvinar

Event Abstract Back to Event MEG Detects Alpha-Power Modulations in Pulvinar Yohan Attal1*, Jérôme Yelnik2, Eric Bardinet1, Marie Chupin1 and Sylvain Baillet3 1 Massachusetts General Hospital, United States 2 Hopital Pitie-Salpetriere, INSERM U679, France 3 Medical College of Wisconsin, United States Objectives: Neuroimaging evidence regarding the functional organization of subcortical nuclei such as pulvinar is rather scarce compared to cortical structures [1]. Further, MEG is often believed to be insensitive to deeper brain structures. We have recently developed a global-brain MEG model that encompasses structural and electrophysiological properties of cortical and subcortical structures for source analysis [2]. Here we use this model to map the brain structures involved in the modulation of brain activity in the alpha range in 6 subjects. Methods and Results: Individual T1-weighted MRI axial scans (1x1x1.5mm voxel size) from 6 healthy subjects were processed to extract cortical and subcortical tessellations. Neocortical and hippocampus surface tessellations were obtained using the automatic pipeline available in the BrainVISA free software solutions [3]. Central grey nuclei were segmented from the individual MR volumes using a deformable atlas approach [4]. Elementary current dipoles (ECD) were placed at the surface of the cortex and hippocampus and along regular volumic grids within subcortical nuclei. The MEG session consisted of a block-designed “eyes open - eyes closed” paradigm (CTF Omega whole-head 151-channel MEG system). Each block lasted for 30 s. Data were band-pass filtered within the alpha band that was determined on an individual basis after inspection of the power spectra of each subject. Distributed source imaging was performed using BrainStorm. Significant ( , non-parametric permutation tests [5]) modulations of MEG source amplitudes were detected by contrasting the eyes open vs. eyes closed conditions. These amplitude modulations were detected in the dorsal and lateral parietal cortex and in the pulvinar thalamic regions. These areas are densely interconnected and generally assumed to be involved in the generation and modulation of alpha brain waves. Conclusions: The global source model has been evaluated on experimental MEG data on a classical eyes-open/eyes-closed paradigm. Modulations of activities were detected in parieto-occipital cortical regions and in the pulvinar part of the thalamus. These results indicate that complete, realistic modelling of MEG source distribution can help detect activation in deeper brain structures that were thought to be invisible to MEG.

Dances with Darwin, 1875–1910: Vernacular Modernity in France by Rae Beth Gordon

MLR, 105.3, 2010 877 and 1890s. The role of Le Figaro inRodenbach's career is particularly significant, since itoffered a stage upon which he could initially reveal his journalistic and, later,his literary talent, through the form of thefeuilleton?%. strategy also adopted by Zola and Barbey d'Aurevilly. In 1892, having written a number of articles for the paper, he published Bruges-la-morte as a feuilleton to popular and critical success. From the perspective of nineteenth-century studies, Rodenbach's texts on literature and painting are, as Gorceix states, significant in the first instance because they offerus 'les impressions, les reactions, prises sur le vif, d'un temoin direct de son epoque' (p. 27). Based mainly on artists and writers living in Paris, essays on Baudelaire, Verlaine, Mallarme, and les Goncourts are accompanied by those on regional writers such asMistral and Brizeux, while the articles on artists are equally wide-ranging, including Rodin, Puvis de Chavannes, Monet, Carriere, and Raffaelli. Rodenbach's admiration for and friendship with many of thewriters and artists he chooses precludes criticism of their shortcomings, yet his perceptive analysis ofMallarme and Rodin, for example, reveals his talent as a critic and in particular for disseminating an understanding of theirwork to a less cultured public. His description of the former's poetic language is telling: cDonc lesmots se taisent; le poete ne les considere plus que comme des signes qui, par la contexture, par la place occupee, par leurmariage avec tel autre precedemment hai, evoquent des sensations vierges, des sens imprevus' (p. 189). Rodenbach's article on Rodin is equally incisive and pedagogical, explaining how he reinvented sculpture through 'la grande loi de la nature [qu'il] a appliquee a toutes ses figures, qui en tirent leur supreme accent de vie' (p. 256). In terms of Rodenbach's own oeuvre, the annex of his writings on Flanders, destined for a Parisian public, is also illuminating. On the one hand, the themes and images ofmisted landscapes, mystical abbeys, and silentmedieval towns recall those of his literary texts; on the other, however, these are self-sufficientand absorbing travel guides which conjure up the exoticism of Rodenbach's native land. Gorceix's edition of Rodenbach's texts thus offers a welcome addition not only to the study of the writer himself, but also to the dissemination and reception of thework of his contemporaries, as well as to the field of nineteenth-century travel literature. Queen's University Belfast Claire Moran Dances with Darwin, 1875-1910: Vernacular Modernity inFrance. By Rae Beth Gordon. Farnham: Ashgate. 2009. 311pp. ?60. ISBN 978-0-7546-5243-4. Dances with Darwin picks up where Rae Beth Gordon's wittily entitled and en grossing Why theFrench Love Jerry Lewis (Stanford, CA: Stanford University Press, 2001) leftoff.An erstwhile performer herself in Paris cafes-concerts, she extends her research here intovarious forms of show-business grotesquerie (inmusic halls, circuses, fairgrounds, and exhibitions), and links these suggestively to the conco mitant phenomenon of (simplistic) exploitation ofDarwin's theories of evolution: in short, the nineteenth-century obsession with the human zoo, typified outside 878 Reviews France by Barnum and the spectacles he made of freaks. Gordon concentrates on three decades and a bit of French popular culture. In her own words: 'The convergence of primitivism with nervous pathology (e.g. epilepsy or hysteria) in the fin-de-siecle music-hall is a vernacular modernity thatprecedes the same shock inHigh Art by three decades' (p. 4). Stereotyped Darwinism was made familiar to the public not only by the popular press but also by popular entertainers. In effect, Gordon's theme is the numerous ways inwhich, like slang, cultural phenomena filtersocially upwards. Despite or because ofwidespread fears of rampant regression and degeneration (a reverse evolution), audiences responded oftenmimetically to the staged displays of chanteuses epileptiques', a kind of St Vitus's dance thatGordon likens to the pelvic gyrations of Elvis Presley a half-century or so later.The famous dancer Jane Avril was a hysteric patient at La Salpetriere mental hospital, where she discovered her vocation; Sarah Bernhardt less riskily studied alleged hysteria in preparation for a stage part. Maurice Chevalier started his career as a comique idiot. There...

Bengt Jangfeldt, Axel Munthe: the road to San Michele, translated by Harry Watson, London and New York, I B Tauris, 2008, pp. ix, 383, illus., £25.00 (hardback 978-1-84511-720-7).

Dr Axel Munthe (1857–1949) is best known as the author of The story of San Michele (London, John Murray, 1929), a book translated into some forty languages, which has fascinated readers across the world. In a semi-fictional autobiography the elderly Munthe presented himself as an old hermit, retired from medical practice to a mystical retreat on the isle of Capri. The adventures and sentiments of the hero in The story of San Michele were a construction of an alternative life, that of an ideal physician, ever available to his patients, never charging for his services, modelling his life on St Francis, and a benevolent protector of animals. This book and probably also Munthe’s earlier Letters from a mourning city (London, John Murray, 1887, 1899) about volunteer work during a cholera epidemic in Naples inspired many men and women to good deeds in medical service. Munthe did not publish in medical journals. His early fiction, however, provides some interesting glimpses into the practice of medicine a century ago. Bengt Jangfeldt’s biography Axel Munthe: the road to San Michele is a valuable contribution to the publications in English about the medical man Axel Munthe, who developed into a literary personality. Drawing on a treasure trove of Munthe’s preserved private correspondence and other sources, Jangfeldt has meticulously traced his life’s journey and professional career. The younger son of an apothecary in Sweden, Munthe’s brief medical education in Montpellier and Paris prepared him for work as an obstetrician, but he fashioned himself as a nerve doctor, claiming that he had trained under Jean-Martin Charcot at La Salpetriere. His attempts to build a medical practice in Paris in the 1880s failed, but he was assisted to set up practice at Piazza di Spagna in Rome and became a sought-after physician among English, American and Scandinavian expatriates in the 1890s. Munthe retired, a wealthy man, to the isle of Capri, where he would have his main residence for forty years. On Capri he had already built the Villa San Michele, presently a popular tourist attraction. In the private realm, Munthe experienced two failed marriages. With his English second wife Hilda, nee Pennington Mellor, Munthe had two sons. For thirty years he maintained a close relationship with Queen Victoria of Sweden, a relationship lasting until her death in 1930. Munthe left Capri in 1943 and spent the remaining years of his life in an apartment at the Royal Palace in Stockholm. Jangfeldt’s main focus is on the Anglophile, cosmopolitan Munthe’s personal life and the social milieux in which he moved. Jangfeldt’s fascination with Munthe’s ascent into high society—diplomatic circles, nobility, and the network of royal families in Europe a hundred years ago—and Munthe’s stance in the two world wars conveys empathy and thrill. Sweden does not have a great biographical tradition on a par with France or Britain. Jangfeldt’s work in this genre is therefore a first. Lytton Strachey pointed out in his preface to Eminent Victorians that a biographer has two duties: to preserve, and to lay bare, to expose. Jangfeldt excels in the first task, but he is not a critical historian who cynically examines his findings to uncover a truth less seductive to a romantic imagination than the first, fresh impressions. Nevertheless, a reader interested to learn about the life of a high society physician a hundred years ago will be well entertained by Jangfeldt’s rendition of Axel Munthe’s story.

Contribution of ParE Mutation and Efflux to Ciprofloxacin Resistance in Pseudomonas aeruginosa Clinical Isolates

Mechanisms of resistance to fluoroquinolone antibiotics in Pseudomonas aeruginosa are mainly comprised of: 1) alteration in DNA gyrase and topoisomerase IV owing to mutations clustered in the quinolone resistance-determining regions (QRDRs) 1-5 and 2) activation or enhancement of efflux pumps 6-8. We have previously reported gyrA, gyrB and parC mutations 3 in thirty clinical isolates of P. aeruginosa, collected at the Pitie-Salpetriere Hospital 3,9 and resistant to ciprofloxacin (MICs, 2 to 128 μg/ml). We observed that all isolates with a double gyrA-parC mutation displayed high ciprofloxacin MICs. However, some of the strains with a single mutation in gyrA or gyrB also had these high MICs. In the present work, other hypothetical mechanisms, such as mutation in parE and enhanced efflux, were investigated. Total DNA was extracted by the freeze-thaw procedure as previously described 3. parE QRDR was amplified and sequenced for all strains. Analysis of the entire parE sequence was carried out for strains with high ciprofloxacin MICs and no mutations in gyrB, parC or parE QRDR. Primers, nucleotide positions and annealing temperatures (Ta) are listed in Table 1. PCR amplifications were performed as previously described 3. For efflux assay, the MIC of ciprofloxacin was determined by the agar dilution method without and with 20 μg/ml of Phe-Arg-β-naphthylamide (PAβN) (Sigma-Aldrich). Eight of the thirty clinical isolates investigated for the ciprofloxacin resistance mechanism, harbored a mutation in the QRDR of ParE resulting in Asp-419to-Asn substitution (Table 2). These isolates were highly resistant to ciprofloxacin (MIC of 16-32 μg/ml) and harbored the GyrA alteration Thr-83-to-Ile but lacked GyrB and ParC alterations. Two strains were found to carry a ParE change outside the QRDR: one at position 473 (Ala-473-to-Val), and a novel one at position 200 (Val-200-to-Met). Finally, No ParE changes were found in the remaining strains, either those with a low level of resistance (ciprofloxacin MIC 1 μg/ml and 4 μg/ml. Multiple efflux pump systems that extrude quinolones have been described in P. aeruginosa 7,8. Investigation of efflux pump enhancement was undertaken by a phenotypic approach. PAβN has been described as an effective inhibitor of efflux pump in P. aeruginosa 14. For 27 clinical isolates, ciprofloxacin MICs decreased in the presence of PAβN by 2to 64fold. However, for only 7 strains, the decrease in ciprofloxacin MICs was more than 4-fold, indicating that most strains exhibited a natural or moderately enhanced efflux (Table 2). The effect of PAβN on ciprofloxacin MIC was higher in strains with patterns P1 and P3 (4to 64-fold decrease in MICs with 5 strains showing more than a 4-fold decrease) than in strains with patterns P4 to P8 (2to 8-fold reduction in MICs with 2 strains showing a 8-fold decrease). This result is concordant with a previous study on the PAβN effect on a large collection of levofloxacin-resistant clinical strains of P. aeruginosa 15. In conclusion, for most of the P. aeruginosa clinical strains, the high level of resistance to ciprofloxacin REPRINT

Why I joined the research laboratory of Prof. D. Carleton Gajdusek in 1968

Two important milestones in my life: I was born in 1921 to a military family from Languedoc in France; in 1986 I took compulsory retirement after declining to create a new research unit in the Pitie Salpetriere Hospital in Paris. Sometime in between I discovered what hospital life was like,

Corrigendum to “Guideline on antiplatelet and anticoagulation management in cardiac surgery” [Eur. J. Cardiothorac. Surg. 34 (1) (2008) 73–92

Department of Cardiothoracic Surgery, James Cook University Hospital, Middlesbrough, UK Department of Cardiothoracic Surgery, Leiden University Medical Center, Leiden, Netherlands Department of Cardiac Surgery, Vicenzo Hospital, Italy d Institute of Cardiology, La Pitie-Salpetriere Hospital, Paris, France Department of Cardiothoracic Surgery, University Hospital of Liege, Liege, Belgium Department of Cardiothoracic Surgery, Karolinska University Hospital, Stockholm, Sweden Department of Cardiothoracic Surgery, Papworth Hospital, CB23 3RE, Cambridge, UK