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1.
Epidemiol Infect ; 147: e109, 2019 01.
Article in English | MEDLINE | ID: mdl-30869022

ABSTRACT

As part of the evaluation of the French plan for the elimination of measles and rubella, we conducted a seroprevalence survey in 2013, aimed at updating seroprevalence data for people 18-32 years old. A secondary objective was to estimate measles incidence in this population during the 2009-2011 outbreak, and thus estimate the exhaustiveness of measles mandatory reporting. We used a cross-sectional survey design, targeting blood donors 18-32 years old, living in France since 2009, who came to give blood in a blood collecting site. We included 4647 people in metropolitan France, 806 people in Réunion Island and 496 in the French Caribbean. A further 3942 individuals were interviewed in the south-east region of metropolitan France to estimate the exhaustiveness of measles mandatory reporting. One of the main findings of this survey is that the proportion of people 18-32 years old susceptible to both measles and rubella infections remained high in France in 2013, 9.2% and 5.4%, respectively, in metropolitan France, even after the promotion campaigns about vaccination catch-up during and following the major measles epidemic in 2009-2011. Applying our results to French census data would suggest that around 1 million people aged 18-32 years old are currently susceptible to measles in France, despite this age group being one of the vaccination targets of the national measles elimination plan. Another important finding is that only an estimated 45% of the true number of cases in this age group was actually notified, despite notification being mandatory.


Subject(s)
Blood Donors/statistics & numerical data , Disease Outbreaks , Measles/epidemiology , Rubella/epidemiology , Adult , Disease Susceptibility/epidemiology , France/epidemiology , Humans , Incidence , Prevalence , Seroepidemiologic Studies , Young Adult
2.
Vox Sang ; 113(1): 3-12, 2018 Jan.
Article in English | MEDLINE | ID: mdl-29193128

ABSTRACT

Transfusion-transmitted infection risk remains an enduring challenge to blood safety in Africa. A high background incidence and prevalence of the major transfusion-transmitted infections (TTIs), dependence on high-risk donors to meet demand, suboptimal testing and quality assurance collectively contribute to the increased risk. With few exceptions, donor testing is confined to serological evaluation of human immunodeficiency virus (HIV), hepatitis B and C (HBV and HCV) and syphilis. Barriers to implementation of broader molecular methods include cost, limited infrastructure and lack of technical expertise. Pathogen reduction (PR), a term used to describe a variety of methods (e.g. solvent detergent treatment or photochemical activation) that may be applied to blood following collection, offers the means to diminish the infectious potential of multiple pathogens simultaneously. This is effective against different classes of pathogen, including the major TTIs where laboratory screening is already implemented (e.g. HIV, HBV and HCV) as well pathogens that are widely endemic yet remain unaddressed (e.g. malaria, bacterial contamination). We sought to review the available and emerging PR techniques and their potential application to resource-constrained parts of Africa, focusing on the advantages and disadvantages of such technologies. PR has been slow to be adopted even in high-income countries, primarily given the high costs of use. Logistical considerations, particularly in low-resourced parts of Africa, also raise concerns about practicality. Nonetheless, PR offers a rational, innovative strategy to contend with TTIs; technologies in development may well present a viable complement or even alternative to targeted screening in the future.


Subject(s)
Blood Safety/methods , Africa , Blood Donors , Blood Safety/economics , Blood Transfusion/standards , Communicable Disease Control , Communicable Diseases/transmission , Developing Countries , Health Resources , Hepatitis C/blood , Humans , Risk Reduction Behavior
4.
J Immunol Res ; 2015: 361604, 2015.
Article in English | MEDLINE | ID: mdl-25811034

ABSTRACT

The evaluation of the impact of probiotics on host health could help to understand how they can be used in the prevention of diseases. On the basis of our previous studies and in vitro assays on PBMC and Caco-2 ccl20:luc reporter system presented in this work, the strain Lactobacillus kefiri CIDCA 8348 was selected and administrated to healthy Swiss mice daily for 21 days. The probiotic treatment increased IgA in feces and reduced expression of proinflammatory mediators in Peyer Patches and mesenteric lymph nodes, where it also increased IL-10. In ileum IL-10, CXCL-1 and mucin 6 genes were upregulated; meanwhile in colon mucin 4 was induced whereas IFN-γ, GM-CSF, and IL-1ß genes were downregulated. Moreover, ileum and colon explants showed the anti-inflammatory effect of L. kefiri since the LPS-induced increment of IL-6 and GM-CSF levels in control mice was significantly attenuated in L. kefiri treated mice. Regarding fecal microbiota, DGGE profiles allowed differentiation of experimental groups in two separated clusters. Quantitative PCR analysis of different bacterial groups revealed only significant changes in Lactobacillus population. In conclusion, L. kefiri is a good candidate to be used in gut inflammatory disorders.


Subject(s)
Cultured Milk Products/microbiology , Gastrointestinal Microbiome/immunology , Immunity, Mucosal , Lactobacillus/immunology , Animals , Cell Line , Cytokines/biosynthesis , Feces/microbiology , Gene Expression , Gene Expression Regulation , Genes, Reporter , Humans , Immunity, Mucosal/genetics , Immunity, Mucosal/immunology , Immunoglobulin A/immunology , Intestinal Mucosa/immunology , Intestinal Mucosa/metabolism , Intestinal Mucosa/microbiology , Leukocytes, Mononuclear/immunology , Leukocytes, Mononuclear/metabolism , Lymphocyte Subsets/immunology , Lymphocyte Subsets/metabolism , Male , Mice
5.
Ann Fr Anesth Reanim ; 33(12): 664-8, 2014 Dec.
Article in French | MEDLINE | ID: mdl-25458457

ABSTRACT

In nasal and sinus surgery, the anaesthetist must share the operating field with the surgeon and take into account some patients' specific pathologies. Bleeding must be avoided by different means but the accurate gesture of the surgeon, added to the properties of the new anaesthetic drugs, may reduce the risk of this functional surgery.


Subject(s)
Anesthesia/methods , Anesthetics , Nasal Surgical Procedures/methods , Paranasal Sinuses/surgery , Antibiotic Prophylaxis , Humans , Monitoring, Intraoperative
6.
Lupus ; 21(13): 1459-62, 2012 Nov.
Article in English | MEDLINE | ID: mdl-22952321

ABSTRACT

Collapsing glomerulopathy (CG), characterized by collapse of the glomerular capillary loops onto the mesangial stalks is rarely associated to systemic lupus erythematosus (SLE). Recently a genetic predisposition to HIV associated nephropathy (HIVAN) has been shown in Afro-Americans: MYH9 polymorhism in 2008 and then APOL1 variants (G1 and G2 alleles) in 2010 were shown to be strongly associated with HIVAN. We describe here for the first time the association of CG in a young Afro-American female with SLE having a homozygous mutation of APOL1. The clinical history, laboratory findings and immunofluorescence all confirmed a diagnosis of SLE. However, studies for factors associated with collapsing glomerulopathy in other situations were consistently negative. As this Afro-American patient developed a CG, we performed genotyping of APOL1. It was found that she is homozygotic for the G2 allele of APOL1. Despite.


Subject(s)
Apolipoproteins/genetics , Black or African American/genetics , Homozygote , Kidney Glomerulus/pathology , Lipoproteins, HDL/genetics , Lupus Erythematosus, Systemic/genetics , Lupus Nephritis/genetics , Mutation , Apolipoprotein L1 , Biopsy , Female , Fluorescent Antibody Technique , Genetic Predisposition to Disease , Humans , Immunosuppressive Agents/therapeutic use , Lupus Erythematosus, Systemic/ethnology , Lupus Erythematosus, Systemic/pathology , Lupus Erythematosus, Systemic/therapy , Lupus Nephritis/ethnology , Lupus Nephritis/pathology , Lupus Nephritis/therapy , Phenotype , Plasma Exchange , Predictive Value of Tests , Renal Dialysis , Risk Factors , Treatment Outcome , Young Adult
8.
Ann Fr Anesth Reanim ; 31(1): 76-7, 2012 Jan.
Article in French | MEDLINE | ID: mdl-22188775

ABSTRACT

We reported the case of asymptomatic traumatic atlantoaxial dislocation in a 14-year-old woman. Clinical diagnosis of this uncommon dislocation is difficult and often made late. The early diagnosis by CT scan is necessary to avoid secondary aggravation. Integrity of the transverse ligament of the atlas is a determining factor for atlantoaxial stability and allows orthopaedic treatment after reduction using moderate traction on the head.


Subject(s)
Atlanto-Axial Joint/injuries , Atlanto-Axial Joint/surgery , Adolescent , Female , Humans , Joint Dislocations/surgery , Magnetic Resonance Imaging , Spinal Fusion , Tomography, X-Ray Computed , Traction
9.
Vox Sang ; 102(4): 354-61, 2012 May.
Article in English | MEDLINE | ID: mdl-22092160

ABSTRACT

BACKGROUND AND OBJECTIVES: Several pathogen inactivation methods currently applied to therapeutic plasma may result in products with different hemostatic properties. This study aims at evaluating and comparing the hemostatic potential of different therapeutic plasma preparations currently available in France. MATERIALS AND METHODS: We studied three types of pathogen-reduced plasma for transfusion (MB/light, Amotosalen/UVA, industrial S/D plasma). Quarantine, non-pathogen-reduced plasma, was used as a control. This study compared more specifically the content in FVIII, fibrinogen (clottable and antigen assays) and ADAMTS-13 and evaluated the intrinsic hemostatic properties using a thrombin generation test [Calibrated Automated Thrombogram (CAT)] at high and low concentrations of tissue factor to assess the maximum quantity of thrombin generated or the contribution of FVIII and FIX in the amplification phase of thrombin generation, respectively. RESULTS: The median FVIII concentration was >70 IU/dl for each preparation. Endogenous thrombin potential values were significantly different among the methods of plasma preparation (P<0·001) but were all in the range of the values measured in donors' plasma. Control by the thrombomodulin-activated protein C system was preserved in all preparations (>50% inhibition of endogenous thrombin potential). Fibrinogen concentrations were all within normal range but fibrinogen levels were lower in the plasmas treated with photochemical methods. ADAMTS-13 levels were preserved. CONCLUSION: The hemostatic potential appears well preserved in all therapeutic plasmas tested but there are some differences between preparations, the clinical relevance of which remains to be elucidated.


Subject(s)
Hemostasis , Plasma , Thrombin/biosynthesis , ADAM Proteins/blood , ADAMTS13 Protein , Factor VIII/analysis , Fibrinogen/analysis , France , Humans , Plasma/chemistry , Plasma/microbiology
10.
Ann Fr Anesth Reanim ; 30(12): 930-2, 2011 Dec.
Article in French | MEDLINE | ID: mdl-22040868

ABSTRACT

The Northern French Alps Emergency Network (RENAU) has a main objective the improvement of the quality of the care in the field of the emergency medical treatment. With this French medical system, we developed a procedure allowing the detachment of a medical-surgical team of the university hospital to help general hospital team in the event of immediate vital emergency situation with untransportable patient. We reported the successful implementation of this support strategy for a 51-year-old patient arrived in a hospital of the network in extremely serious hemodynamic shock due to an important hemorrhagic pericardial effusion with tamponnade 1 day after percutaneous closure of the patent foramen ovale (PFO).


Subject(s)
Cardiac Tamponade/surgery , Emergency Service, Hospital/organization & administration , Emergency Treatment , Female , France , Humans , Middle Aged , Patient Care Team
11.
Rev Med Suisse ; 7(308): 1769-73, 1775, 2011 Sep 14.
Article in French | MEDLINE | ID: mdl-21954819

ABSTRACT

Humanitarian Medicine's practical experiences show the potential violence of the medicine's power over bodies everywhere. The inequality between assistance and people receiving benefits is comparable to the asymmetrical relationship between doctor and patient. Efforts have to be done in order to comprehend other possibilities of life's organization. The understanding of double subjectivities in the therapeutic relationship is a requirement for success, in any situation--as usual. Furthermore, the adverse effects of assistance remind us the primary principle not to harm. These admissions of failure urge to develop assessment reasoning, including all factors of influence on health (resources, policy...), and an approach which aims people to become self-sufficient.


Subject(s)
Cooperative Behavior , General Practice/standards , Altruism , Humans , Interdisciplinary Communication , Medicine/standards , Physician-Patient Relations , Switzerland
12.
Ann Fr Anesth Reanim ; 30(10): 730-3, 2011 Oct.
Article in French | MEDLINE | ID: mdl-21704475

ABSTRACT

OBJECTIVES: The main objective was to estimate the nature, severity and medical care of severe trauma injuries following mountain activities as compared to severe trauma following traffic accident in a mountain area. STUDY DESIGN: We conducted a prospective comparative monocentric observational study at a University Hospital located in the northern Alps area, using the First national study database (French intensive care recorded in severe trauma). PATIENTS AND METHODS: Three hundred and thirty-seven patients were included during a 2-year-period from January 2005 to December 2006. Three hundred and thirty-seven patients, including 223 traffic accidents and 114 mountain accidents were included. The survey data was achieved with a standardized method on a period of 30 days after the accident, and recorded in a computerized file for optimal completeness. RESULTS: The study did not show higher severity or mortality rates in patients with mountain accidents. In both groups, we found a peak of mortality for young adults and similar causes of death. However, spinal cord injuries were statistically more frequent in mountain accidents. CONCLUSION: So, it seems important to continuously warn population about dangers of this playground.


Subject(s)
Mountaineering/injuries , Skiing/injuries , Wounds and Injuries/epidemiology , Accidents, Traffic/statistics & numerical data , Adult , Age Factors , Cause of Death , Emergency Medical Services , Female , France/epidemiology , Humans , Injury Severity Score , Male , Middle Aged , Spinal Cord Injuries/epidemiology , Transportation of Patients , Young Adult
13.
Ann Fr Anesth Reanim ; 28(2): 135-9, 2009 Feb.
Article in French | MEDLINE | ID: mdl-19211218

ABSTRACT

INTRODUCTION: Patients with moderate traumatic brain injury (TBI) (Glasgow Coma Scale, GCS, 9-13) or minor TBI (GCS 14-15) are at risk for subsequent neurological deterioration. Serum protein S-100 is believed to reflect brain damage following TBI. In patients with normal or minor CT scan abnormalities on admission, we tested whether the determination of serum protein S-100 beta could predict secondary neurological deterioration. METHODS: Sixty-seven patients with moderate or minor TBI were prospectively studied. Serum samples were collected on admission within 12 hours postinjury to measure serum protein S-100 levels. Neurological outcome was assessed up to seven days after trauma. Secondary neurological deterioration was defined as two points or more decrease from the initial GCS, or any treatment for neurological deterioration. RESULTS: Nine patients had a secondary neurological deterioration after trauma. No differences in serum levels of protein S-100 were found between these patients and those without neurological aggravation (n=58 patients): 0.93 microg/l (0.14-4.85) vs 0.39 microg/l (0.04-6.40), respectively. The proportion of patients with abnormal levels of serum protein S-100 at admission according to two admitted cut-off levels (>0.1 and >0.5 microg/l) was comparable between the two groups of patients. Elevated serum levels of protein S-100 were found in patients with Injury Severity Score (ISS) of more than 16 (n=23 patients): 1.26 microg/l (0.14-6.40) vs 0.22 microg/l (0.04-6.20) in patients with ISS less than 16 (n=44 patients). DISCUSSION: The dosage of serum protein S-100 on admission failed to predict patients at risk for neurological deterioration after minor or moderate TBI. Extracranial injuries can increase serum protein S-100 levels, then limiting the usefulness of this dosage in this clinical setting.


Subject(s)
Brain Injuries/blood , Nerve Growth Factors/blood , S100 Proteins/blood , Adolescent , Adult , Aged , Aged, 80 and over , Biomarkers , Brain Injuries/complications , Confounding Factors, Epidemiologic , Disease Progression , Female , Glasgow Coma Scale , Humans , Male , Middle Aged , Multiple Trauma/blood , Predictive Value of Tests , S100 Calcium Binding Protein beta Subunit , Trauma Severity Indices , Young Adult
15.
Am J Transplant ; 8(9): 1901-10, 2008 Sep.
Article in English | MEDLINE | ID: mdl-18671673

ABSTRACT

We have analyzed the evolution of renal status beyond the perioperative period in patients with cystic fibrosis (CF) undergoing lung transplantation and presented histological analysis of 15 patients biopsied for an episode of accelerated renal function loss (RFL). Episodes of accelerated RFL after the perioperative period occurred in 32.5% of patients and significantly raised the risk of end-stage renal disease (ESRD) (p < 0.001). The histologic lesions associated with these episodes differed according to the time of onset. Early onset (10 cases) was associated with tubulointerstitial lesions in the form of oxalate nephropathy (50%) and/or a pigmented tubulopathy (80%). This latter was correlated with treatment with antiviral agents (p = 0.002) and aminoside and glycopeptide antibiotics (p = 0.03) administered in the month preceding biopsy. Lesions in late episodes of accelerated RFL (5 cases) were principally vascular: arteriosclerosis and arteriolosclerosis (p = 0.007, p = 0.00002), correlated with diabetic glomerulosclerosis or focal segmental glomerulosclerosis in the absence of prominent diabetic changes. Specific calcineurin-inhibitor nephrotoxicity was present in 93.3% of biopsies associated with thrombotic microangiopathy in 46.7% of cases. The identification of specific etiologies of progressive kidney disease in patients with CF after lung transplantation should permit more effective post-transplant care of these patients.


Subject(s)
Cystic Fibrosis/complications , Kidney Glomerulus/pathology , Kidney Tubules/pathology , Kidney/pathology , Lung Transplantation , Biopsy , Cyclosporine/adverse effects , Diabetic Nephropathies/etiology , Diabetic Nephropathies/pathology , Diabetic Nephropathies/surgery , Glomerular Filtration Rate , Glomerulosclerosis, Focal Segmental/etiology , Glomerulosclerosis, Focal Segmental/pathology , Glomerulosclerosis, Focal Segmental/surgery , Humans , Immunosuppressive Agents/adverse effects , Kidney/drug effects , Kidney/surgery , Kidney Glomerulus/drug effects , Kidney Glomerulus/surgery , Kidney Tubules/drug effects , Kidney Tubules/surgery , Retrospective Studies , Tacrolimus/adverse effects
16.
Ann Fr Anesth Reanim ; 27(3): 256-60, 2008 Mar.
Article in French | MEDLINE | ID: mdl-18314297

ABSTRACT

Amphetamines are considered as narcotics in France. Their use induces modifications of the central nervous system and of the cardiovascular, respiratory and urinary systems by a sympathomimetic indirect effect. Here is reported the observation of a young woman who absorbed amphetamines causing a cardiogenic shock on a ground of acute myocarditis. The constitution of haemodynamic, respiratory and neurologic distresses lead to the endotracheal intubation of the patient. The haemodynamic status remaining shaky, despite the use of vasoactive drugs, a circulatory assistance by intra-aortic counter pulsation balloon was carried out. The initial echocardiography showed a left ventricular ejection fraction lower than 20%. Amphetamine's toxicity mechanisms still remain complicated; on cardiovascular plan, some cases of coronary artery spasm have been described. The coronarography, not accomplished immediately, was normal. Toxicological samples revealed an abnormally high amphetamines concentration. The severity of the cardiac attack was amplified by a Mycoplasma pneumoniae myocarditis. There was a positive evolution in eight days. Intoxication and infection can difficultly be dissociated in this case of cardiogenic shock.


Subject(s)
Amphetamines/poisoning , Mycoplasma Infections/complications , Shock, Cardiogenic/chemically induced , Adult , Amphetamines/blood , Amphetamines/urine , Female , Heart Rate , Humans , Hypertension/physiopathology , Shock, Cardiogenic/complications , Treatment Outcome
17.
Ann Fr Anesth Reanim ; 27(1): 90-3, 2008 Jan.
Article in French | MEDLINE | ID: mdl-18068944

ABSTRACT

We report the case of a 29-year-old female who presented with a series of major vascular complications in rapid succession: haemothorax following rupture of a mammary artery aneurysm, pulmonary embolism, anterior myocardial infarction secondary to spontaneous dissection of the left anterior descending artery and rupture of a false aneurysm of the splenic artery. A diagnosis of Ehlers-Danlos syndrome (vascular variant) was considered the most likely in this context. Characterized by an extreme vascular fragility, this rare disease poses important clinical management issues for the anaesthetist and intensive care physician.


Subject(s)
Aneurysm, Ruptured/etiology , Aortic Dissection/etiology , Coronary Aneurysm/etiology , Ehlers-Danlos Syndrome/complications , Hemothorax/etiology , Myocardial Infarction/etiology , Pulmonary Embolism/etiology , Adult , Aneurysm, False/etiology , Comorbidity , Ehlers-Danlos Syndrome/diagnosis , Emergencies , Female , Genetic Predisposition to Disease , Humans , Mammary Arteries/pathology , Rupture, Spontaneous , Splenic Artery/pathology
18.
Ann Fr Anesth Reanim ; 26(11): 959-64, 2007 Nov.
Article in French | MEDLINE | ID: mdl-18029139

ABSTRACT

Adequate instruments for measuring patient outcome after subarachnoid aneurysmal haemorrhage (SAH) are required to interpret results of clinical trials before making clinical recommendations. Graded measures are generally used, e.g. Glasgow Outcome Scale (GOS) and the modified Rankin Scale (mRS). However, these scales are inappropriate to measure cognitive dysfunction, particularly in patients with good outcome. We investigated the most frequent complains, the working status and the self-assessment of handicap (quality of life) in GOS-5 patients after their surgical treatment of a ruptured aneurysm. A questionnaire was sent to 126 patients one year following their discharge from hospital. The questionnaire assessed their motor activity, vitality and psychological troubles and handicap. Over 84 patients with GOS-5, 55 (65%) had persistent cognitive and psychological troubles including memory deficit, vitality and depressive troubles. Providing the use of combined scales to assess handicap and quality of life, these results suggest that SAH can result in a persistent alteration of cognitive function in patients, even in those classified as having a good outcome using the routine graded scales.


Subject(s)
Aneurysm, Ruptured/surgery , Intracranial Aneurysm/physiopathology , Intracranial Aneurysm/surgery , Subarachnoid Hemorrhage/physiopathology , Subarachnoid Hemorrhage/surgery , Affect , Aneurysm, Ruptured/physiopathology , Aneurysm, Ruptured/psychology , Anxiety , Glasgow Coma Scale , Humans , Intracranial Aneurysm/psychology , Memory Disorders/epidemiology , Quality of Life , Retrospective Studies , Subarachnoid Hemorrhage/psychology , Surveys and Questionnaires , Treatment Outcome
19.
Med Mal Infect ; 37(11): 762-4, 2007 Nov.
Article in French | MEDLINE | ID: mdl-17888603

ABSTRACT

We report a case of severe pneumonia due to Chryseobacterium indologenes in an immunocompetent patient. Chryseobacterium indologenes (formerly Flavobacterium indologenes) are saprophytic Gram-negative rods widely distributed in damp environment. Many sites of infection were described in the literature. These infections are always severe sometimes associated to multiple organ failure. The evolution is usually favorable with antibiotic treatment. Bacteria characteristically grow as yellow-pigmented colonies. They are naturally resistant to many antimicrobial agents. They are usually susceptible to piperacillin(DCI) alone or combined with tazobactam(DCI), ceftazidime(DCI), cefepime(DCI), fluoroquinolones(DCI), rifampin(DCI) and cotrimoxazole(DCI), but the in vitro susceptibility to these antibiotics should be systematically tested. Nevertheless, the optimum antibiotic treatment for Chryseobacterium-related infections remains to be established. In the case we report, the diagnosis was made according to the results of bronchial sample bacterial culture. This case report underlines the need for specific management of patients infected with this species.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Chryseobacterium , Flavobacteriaceae Infections/immunology , Immunocompetence , Adult , Chryseobacterium/drug effects , Chryseobacterium/isolation & purification , Female , Humans , Microbial Sensitivity Tests
20.
Encephale ; 33(2): 179-87, 2007.
Article in French | MEDLINE | ID: mdl-17675913

ABSTRACT

Citalopram, a selective serotonin reuptake inhibitor, is composed of 2 enantiomers, R-citalopram and S-citalopram, 2 different non-superimposable mirror image forms of the same molecule. Separating these 2 enantiomers has enabled studying their individual properties. Citalopram's pharmacologic activity is centered on the S enantiomer's high affinity for the serotonin transporter which is twice as high as citalopram's and 30 to 40 times higher than R-citalopram. This leads to an inhibition of serotonin reuptake two times higher for escitalopram compared with citalopram and confirms that citalopram's pharmacologic activity is due to the S-enantiomer. Contrary to what might be expected, the effect of escitalopram (DCI of S-citalopram) is not superimposable on an equivalent dose of citalopram but is superior. Several hypotheses could explain this superiority. First, conversions of the S-enantiomer into the R-enantiomer may occur, but there is no reason why this phenomenon would happen more when both enantiomers are present than when escitalopram is alone. Furthermore, pharmacokinetic studies have shown that S or R configurations are stable in vivo. Second, a particular action of R-citalopram may influence the S-enantiomer's kinetic from intestinal absorption to blood-brain barrier. But concentrations of both enantiomers in the frontal cortex are the same. Therefore, R-citalopram does not interfere with escitalopram's kinetic. Finally, interactions may appear at the synaptic level. Results of experimentation, after in situ injection to the cortex level, confirm that an interaction between the 2 enantiomers takes place at that level. A direct negative interaction of R-citalopram on one or several effectors that create the antidepressive effect seems justified. This negative interaction has been studied in depth. Animal models have shown that the R-enantiomer has no antidepressive potential and when associated with escitalopram prohedonic effects disappear. Escitalopram is more powerful than citalopram in reducing anxiety but the presence of R-citalopram reduces the positive effects of escitalopram. We then may conclude that R-citalopram antagonizes the antidepressive effects of escitalopram and that its presence limits the therapeutic effect and reduces the speed of action of citalopram. The antagonism of escitalopram by R-citalopram was not expected and one hypothesis is that a direct interaction between the 2 enantiomers may occur on a particular site of the serotonin transporter. Results have shown that R-citalopram has a significant affinity only for the allosteric site of the transporter, which regulates the affinity of the ligand for the active site at the origin of serotonin reuptake inhibition. Unlike citalopram, escitalopram's pharmacologic action is not blocked by R-citalopram explaining its greater therapeutic efficacy and more rapid mode of action.


Subject(s)
Anxiety Disorders/drug therapy , Citalopram/chemistry , Depressive Disorder, Major/drug therapy , Selective Serotonin Reuptake Inhibitors/chemistry , Depressive Disorder, Major/psychology , Humans , Stereoisomerism , Treatment Outcome
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