La découverte de l'insuline.

The first therapeutic benefits of insulin were recorded after the injection of pancreatic extract, given on January 23, 1922 in Toronto to a 14-year-old teenager. Until then, type I diabetes was always fatal, within weeks or months; the fatal outcome being delayed only at the cost of a drastic low-calorie diet. In previous decades, the importance of the pancreas in the development of diabetes had been pointed out, but all attempts to use a pancreatic extract had failed. It is with the objective of "neutralizing" the destructive effects of pancreatic juice (proteolytic) that the isolation of insulin was carried out by a research team which was totally improbable since it was headed by an orthopedic surgeon, Frederick Banting and a 22-year-old stagiaire, Charles Best. Their work was carried out in the university physiology laboratory of John Macleod and their outcome was made possible thanks to the skills of James Collip who purified the insulin preparation. Scientific reality invites us to emphasize that, Banting works, based on a wrong hypothesis, drew towards an historical discovery. Very quickly recognized as of major importance for medicine, the discovery was greeted by the attribution of the Nobel Prize in 1923. For a hundred years, insulin has not ceased to be an essential drug for tens of millions of patients in the world, but it has been a motor for scientific research: innovation in galenic pharmacy and biopharmacy, in fundamental chemistry as a subject for the study of the structure, analysis and synthesis of proteins, and finally, as a motor for the development of biotechnologies, since insulin was the first drug prepared by DNA-recombinant technology, and marketed in 1982.

Clearance of carbapenem-resistant Enterobacteriaceae vs vancomycin-resistant enterococci carriage after faecal microbiota transplant: a prospective comparative study.

BACKGROUND: Carbapenem-resistant Enterobacteriaceae (CRE) and vancomycin-resistant enterococci (VRE) carriage are increasing worldwide. Faecal microbiota transplantation (FMT) appears to be an attractive option for decolonization. This study aimed to evaluate CRE vs VRE clearance by FMT among carriers. METHODS: A multi-centre trial was undertaken on patients with CRE or VRE digestive tract colonization who received FMT between January 2015 and April 2017. Adult patients with CRE or VRE colonization, confirmed by three consecutive rectal swabs at weekly intervals, including one in the week prior to FMT, were included in the study. Patients with immunosuppression or concomitant antibiotic prescription at the time of FMT were excluded. Successful decolonization was determined by at least two consecutive negative rectal swabs [polymerase chain reaction (PCR) and culture] on Days 7, 14, 21 and 28, and monthly for three months following FMT. RESULTS: Seventeen patients were included, with a median age of 73 years [interquartile range (IQR) 64.3-79.0]. Median duration of carriage of CRE or VRE before FMT was 62.5 days (IQR 57.0-77.5). One week after FMT, three of eight patients were free of CRE colonization and three of nine patients were free of VRE colonization. After three months, four of eight patients were free of CRE colonization and seven of eight patients were free of VRE colonization. Qualitative PCR results were concordant with culture. Six patients received antibiotics during follow-up, three in each group. No adverse events were reported. CONCLUSION: CRE and VRE clearance rates were not significantly different in this study, possibly due to the small sample size, but a trend was observed. These data should be confirmed by larger cohorts and randomized trials.

Is faecal microbiota transplantation an option to eradicate highly drug-resistant enteric bacteria carriage?

Carbapenem-resistant Enterobacteriaceae (CRE) or vancomycin-resistant enterococci (VRE) carriage present a major public health challenge. Decolonization strategies are lacking. We aimed to evaluate the impact of faecal microbiota transplantation (FMT) on a cohort of patients with digestive tract colonization by CRE or VRE. Eight patients were included: six carrying CRE and two colonized by VRE. One month after FMT, two patients were free from CRE carriage, and another patient was free from VRE after three months. In our experience, this strategy is safe.

[Clinical pharmacist influence at hospital to prevent overdosed prescription of acetaminophen]. / Impact du pharmacien clinicien à l'hôpital pour prévenir les posologies supra-thérapeutiques du paracétamol.

OBJECTIVES: The recommended daily dose of acetaminophen is limited to 60mg/kg/day with a maximum of 3g daily dose in adults weighing less than 50kg or in patients undergoing certain risk factors. This study aimed at assessing the fulfillment of those recommendations and the possible impact on the liver dysfunction at supra-therapeutic doses of acetaminophen. METHODS: This study was performed one day in 9 services. Patients characteristics, acetaminophen dose, daily dose administered, physiopathological aspects, markers of liver damage were collected. RESULTS: Among 542 prescriptions analyzed, 343 of them contained acetaminophen. The median age of patients studied was 81 years and one third weighed less than 50kg. The main risk factor of supra-therapeutic prescriptions was the lack of dose acetaminophen based on weight with 14% patients concerned and this risk raised at 17% when the pathophysiological conditions were included. The presence of pharmacists in medicals departments was more effective than the use of informatics programs limiting the dose systematically to 3g/day, or a distant pharmaceutical validation from care services to reduce the risk of acetaminophen overdose. According to the statement of administrations, only 4 of 49 patients received doses above 60mg/kg/day with a low impact on liver function tests. CONCLUSION: The continuous presence in pharmaceutical care services was the most effective measure to ensure effective implementation of acetaminophen recommendations.

[Cyclosporine eye drops: A 4-year retrospective study (2009-2013)]. / Collyres de ciclosporine : étude d'une cohorte de patients de 2009 à 2013.

INTRODUCTION: The University Hospitals Paris Centre Pharmacy compounds three concentrations of cyclosporine eye drops: 20mg/mL (=2%); 5mg/mL (=0.5%) and 0.5mg/mL (=0.05%). Cyclosporine A 2% drops were developed in 1995 to prevent the rejection of high-risk cornea transplants after failure of topical steroids. The other concentrations of eye drops were developed for the treatment of various immune or inflammatory diseases of the cornea, conjunctiva and uvea. These eye drops are dispensed with a physician's prescription to hospitalized or ambulatory patients. A retrospective study over 4 years (2009-2013) was conducted to analyze the details of prescription and possible adverse events. MATERIALS AND METHODS: Dispensations made from January 1st, 2009 through December 31st, 2013 were studied, including patient age, dose of cyclosporine and practice location of prescribing physician. We also recorded the indications for cyclosporine eye drops in a sample of ambulatory patients. The analysis of local tolerability and the effect on visual comfort was based on questionnaires sent to the patients on cyclosporine 2% over a period of 2 months. RESULTS: Cyclosporine eye drops prescription grew continuously from 2009 through 2013 for all concentrations. In 2013, 5,859 patients were treated, among which 3,616 patients with topical cyclosporine 2%, 1,681 patients with 0.5%, and 562 patients with 0.05%. In total, this represents 62,621 eye drops. Treated patients ranged from 1 week to 100 years old. Topical 2% cyclosporine is indicated in 61% of cases to prevent high-risk corneal graft rejection. Other indications are corneal ulcer (6%), atopic keratoconjunctivitis (5%), vernal keratoconjunctivitis (5%) and herpetic keratitis (4%). Topical 0.5% cyclosporine is prescribed primarily for dry eye syndrome (20%) and to prevent rejection of high-risk corneal transplantation (11%), to treat ocular rosacea (10%), vernal keratoconjunctivitis (10%), atopic keratoconjunctivitis (8%) and Sjögren's syndrome (7%). Topical 0.05% cyclosporine is prescribed primarily for dry eye syndrome resistant to conventional treatment (47%) and Sjögren's syndrome (21%). Local tolerability of topical cyclosporine was evaluated in 388 patients. The majority of patients (63%) did not experience any adverse effects. The main side effects are redness, burning sensation and itching. CONCLUSION: Prescription of various formulations of topical cyclosporine is current practice for surgical indications: rejection of high-risk corneal transplantation; or medical indications: vernal or atopic keratoconjunctivitis and dry eye syndrome. Further prospective randomized studies would be necessary to validate formulations, doses and indications of cyclosporine eye drops.

[Fecal microbiota transplantation in recurrent Clostridium difficile infections. Framework and pharmaceutical preparation aspects]. / Le transfert de microbiote fécal lors d'infections récidivantes à Clostridium difficile. Cadre et aspects pharmacotechniques.

The fecal microbiota transplantation consists in introducing a preparation constituted by a dilution of stools of a healthy donor in the digestive tract of a patient recipient, to restore his intestinal physiological balance. This therapeutic approach was the subject of numerous studies showing its efficiency in the treatment of the recurrent infections with Clostridium difficile. The fecal microbiota transplantation has now a high level of clinical evidence, which explains that it appears in various international recommendations. In France, the fecal microbiota transplantation responds to the definition of a medication and can be executed as a pharmaceutical preparation or as an experimental drug for clinical trials under the responsibility of a hospital pharmacy. The objective of this paper is to propose a definition of a framework and to describe the methods of preparation of the fecal microbiota transplantation in the treatment of the recurrent infections with C. difficile and the interactions to consider for hospital pharmacies that do not have technical means to operate this technique.

[History of corticotherapy]. / Histoire de la corticothérapie.

Corticosteroids emerged in the late 1940s, at a time when steroid chemistry began to offer new therapeutic approaches. Extractive chemistry (T. Reichstein), chemical synthesis (E.C. Kendall) and clinical investigations (P. Hench) were combined to result in the discovery of cortisone in 1948, leading to a long series of related derivatives. Besides their first applications to treat Addison's disease and rheumatic or inflammatory diseases, corticosteroids could easily correct many metabolic and functional symptoms. Fluoridation of the steroid skeleton allowed the development of more active and better tolerated molecules. Corticosteroids have revolutionized the treatment of allergic diseases or immunity troubles, graft rejection, many dermatological, respiratory, digestive, eye diseases, etc. It is used today in all areas of therapeutic.

[Successful treatment of resistant Fusarium solani keratitis with liposomal amphotericin B]. / Efficacité de l'amphotéricine B liposomale dans le traitement d'une kératite àFusarium solani résistante.

INTRODUCTION: The prognosis for Fusarium keratitis is poor. Effective drugs to treat this infection are therefore needed. CASE REPORT: A patient presented Fusarium solani keratitis. The infection regressed with topical amphotericin B and intravenous voriconazole. Topical steroids were introduced. There was reactivation and extension of the infection, invading the anterior chamber. Steroids were discontinued and the antifungal treatment was restarted but there was continued deterioration. Recovery was achieved without surgery, with topical voriconazole, topical liposomal amphotericin B, topical natamycin, intravenous liposomal amphotericin B, and intravenous voriconazole. CONCLUSION: Combined orally and topically administered voriconazole is a promising therapy when the minimum inhibitory concentration is approximately 2 microg/ml. Liposomal amphotericin B seems to be the most effective drug for the different infection stages. Posaconazole is a useful alternative but further investigations must be pursued.

[The story of Annales pharmaceutiques françaises. 1809-2009]. / L'histoire des Annales pharmaceutiques françaises. 1809-2009.

The Annales pharmaceutiques françaises is 200 years old. Initially, in 1809, the Bulletin de pharmacie was the organ of the Société de pharmacie de Paris. The journal was one of the dynamic events stimulated by the law of Germinal in year XI of the French revolution (1803). Its readership increased tremendously, rapidly making it the first regular journal in the pharmaceutical world. In 1984 it became the Journal de pharmacie et chimie published for a century. It was in 1943 that the journal took on its current name of the Annales pharmaceutiques françaises. The journal is now the official organ of the French National Academy of Pharmacy. The six annual issues are supplemented by an internet diffusion allowing readers access in all French-speaking countries.

[Efficacy of topical 2% cyclosporine A as a steroid-sparing agent in steroid-dependent vernal keratoconjunctivitis]. / Efficacité de la ciclosporine A en collyre à 2% en tant qu'épargneur de corticoïdes dans le traitement de la kératoconjonctivite vernale corticodépendante.

INTRODUCTION: Vernal keratoconjunctivitis (VKC) is responsible for severe conjunctival and corneal inflammation that often requires topical steroids. Steroid dependency is not rare and can lead to unacceptable complications. The aim of this study was to analyze the efficacy of 2% cyclosporine eye drops (CsA) as a steroid-sparing agent in steroid-dependent VKC. PATIENTS AND METHODS: In this noncomparative interventional case series, 18 steroid-dependent VKC patients (17 males, 1 female; mean age, 13 years old) received 2% CsA qid. Topical steroids were associated at decreasing dosage for 1 week and stopped if possible. Efficacy was graded at 1 and 3 months on symptoms, signs and steroid use. Local and systemic tolerability (cyclosporinemia, creatininemia) was also assessed. RESULTS: After 1 month, inflammation was controlled without steroids in 11 cases (61%). Low-dose steroids were still necessary to control the disease in four cases (22%). In three cases (17%), the disease was not controlled despite high-dose steroids. At 3 months, results were similar. All patients whose inflammation was partially controlled or not controlled by CsA had active extraocular atopic diseases. Local and systemic tolerability was excellent. CONCLUSIONS: Topical 2% cyclosporine is inconstantly effective in steroid-dependent VKC. However, this treatment allows for a partial or total reduction of steroids in most cases.

Liposomal amphotericin B eye drops to treat fungal keratitis: physico-chemical and formulation stability.

Local fungal infections with Candida, Fusarium, Curvularia and Aspergillus can lead to serious ulceration of the cornea and must be treated rapidly. The current treatment consists of 0.15% (w/v) amphotericin B eye drops prepared from Fungizone, containing deoxycholate, irritant for the cornea, which reduces patient compliance. Eye drops based on liposomal amphotericin B (AmBisome would be a convenient alternative; however, according to the manufacturer's instructions, AmBisome can only be kept refrigerated for 1 week after reconstitution. A longer shelf-life at ambient temperature would be preferable for a preparation made in a hospital pharmacy and delivered to patients. Thus, the possibility of storing an ophthalmic preparation of 0.5% (w/v) liposomal amphotericin B after reconstitution was investigated. After 6 months at room temperature or at +2-8 degrees C, the hydrodynamic diameter measured by quasi-elastic light scattering remained constant at 108 +/- 30 nm with a polydispersity index lower than 0.15. Amphotericin B content, checked by a validated HPLC method, was maintained between 94 and 107%. Amphotericin B and soy phosphatidylcholine proportions remained constant, indicating that the liposomes remained intact and retained the drug. These results show the feasibility of an ophthalmic preparation based on liposomal amphotericin B developed in hospital pharmacies.

[John Vane, 1927-2004, the pharmacologist of the vascular endothelium [corrected]]. / John R. Vane, "pharmacologue de l'endothélium vasculaire", 1927-2004.

The work of John Vane greatly contributed to the use of aspirin in cardiology. The impact of aspirin administration at low dose for the prevention of stroke or coronary attack results from its effect on enzymes regulating the production of prostaglandins. After understanding the mechanism of interaction between aspirin and the vascular endothelium, Vane proposed assigning a major physiological function to the vascular endothelium which then became a pharmacological target for new drugs. Using an ingenious "real time" biological assay of bloodstream hormones irrigating an isolated organ called the "blood-bathed organ cascade", John Vane developed a system for highly sensitive monitoring of several mediators like angiotensin, bradykinin and prostaglandins and discovered prostacyclin, a potent platelet aggregation inhibitor. Vane explained anti-inflammatory drugs effects (among which aspirin remains the leader) through their activity on cyclo-oxygenase and inhibition of prostacyclin and thromboxane production. Another cyclooxygenase isoform, so-called type 2, has been discovered in 1991. Thus, besides the constitutive COX-1, participating to stomach protection and renal artery vasodilatation, a COX-2 enzyme is existing, induced by inflammatory phenomenons and cytokines stimulation, allowing to design specific inhibitors "coxibs", playing an increasing but controversial role in the struggle against inflammation. He won Albert Lasker Prize in 1977 and Nobel Prize in medicine and physiology (shared with Sune Bergström and Bengt I. Samuelson) in 1982.