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2.
Transl Psychiatry ; 7(3): e1056, 2017 03 14.
Article in English | MEDLINE | ID: mdl-28291262

ABSTRACT

In animal models of autism spectrum disorder (ASD), the NKCC1 chloride-importer inhibitor bumetanide restores physiological (Cl-)i levels, enhances GABAergic inhibition and attenuates electrical and behavioral symptoms of ASD. In an earlier phase 2 trial; bumetanide reduced the severity of ASD in children and adolescents (3-11 years old). Here we report the results of a multicenter phase 2B study primarily to assess dose/response and safety effects of bumetanide. Efficacy outcome measures included the Childhood Autism Rating Scale (CARS), the Social Responsive Scale (SRS) and the Clinical Global Impressions (CGI) Improvement scale (CGI-I). Eighty-eight patients with ASD spanning across the entire pediatric population (2-18 years old) were subdivided in four age groups and randomized to receive bumetanide (0.5, 1.0 or 2.0 mg twice daily) or placebo for 3 months. The mean CARS value was significantly improved in the completers group (P: 0.015). Also, 23 treated children had more than a six-point improvement in the CARS compared with only one placebo-treated individual. Bumetanide significantly improved CGI (P: 0.0043) and the SRS score by more than 10 points (P: 0.02). The most frequent adverse events were hypokalemia, increased urine elimination, loss of appetite, dehydration and asthenia. Hypokalemia occurred mainly at the beginning of the treatment at 1.0 and 2.0 mg twice-daily doses and improved gradually with oral potassium supplements. The frequency and incidence of adverse event were directly correlated with the dose of bumetanide. Therefore, bumetanide improves the core symptoms of ASD and presents a favorable benefit/risk ratio particularly at 1.0 mg twice daily.


Subject(s)
Autism Spectrum Disorder/drug therapy , Bumetanide/administration & dosage , Sodium Potassium Chloride Symporter Inhibitors/administration & dosage , Adolescent , Anorexia/chemically induced , Asthenia/chemically induced , Autism Spectrum Disorder/physiopathology , Autism Spectrum Disorder/psychology , Bumetanide/therapeutic use , Child , Child, Preschool , Dehydration/chemically induced , Dose-Response Relationship, Drug , Female , Humans , Hypokalemia/chemically induced , Male , Sodium Potassium Chloride Symporter Inhibitors/therapeutic use , Treatment Outcome
3.
Mol Psychiatry ; 21(3): 411-8, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26055424

ABSTRACT

Phenotypic and genetic heterogeneity is predominant in autism spectrum disorders (ASD), for which the molecular and pathophysiological bases are still unclear. Significant comorbidity and genetic overlap between ASD and other neurodevelopmental disorders are also well established. However, little is understood regarding the frequent observation of a wide phenotypic spectrum associated with deleterious mutations affecting a single gene even within multiplex families. We performed a clinical, neurophysiological (in vivo electroencephalography-auditory-evoked related potentials) and genetic (whole-exome sequencing) follow-up analysis of two families with known deleterious NLGN4X gene mutations (either truncating or overexpressing) present in individuals with ASD and/or with intellectual disability (ID). Complete phenotypic evaluation of the pedigrees in the ASD individuals showed common specific autistic behavioural features and neurophysiological patterns (abnormal MisMatch Negativity in response to auditory change) that were absent in healthy parents as well as in family members with isolated ID. Whole-exome sequencing in ASD patients from each family identified a second rare inherited genetic variant, affecting either the GLRB or the ANK3 genes encoding NLGN4X interacting proteins expressed in inhibitory or in excitatory synapses, respectively. The GRLB and ANK3 mutations were absent in relatives with ID as well as in control databases. In summary, our findings provide evidence of a double-hit genetic model focused on excitatory/inhibitory synapses in ASD, that is not found in isolated ID, associated with an atypical in vivo neurophysiological pattern linked to predictive coding.


Subject(s)
Autistic Disorder/complications , Autistic Disorder/genetics , Cell Adhesion Molecules, Neuronal/genetics , Evoked Potentials, Auditory/physiology , Genomics , Intellectual Disability/etiology , Acoustic Stimulation , Child, Preschool , Electroencephalography , Evoked Potentials, Auditory/genetics , Family Health , Female , Follow-Up Studies , Genetic Predisposition to Disease , Glutamic Acid , Humans , Male , Severity of Illness Index , Signal Transduction/genetics , gamma-Aminobutyric Acid
4.
Transl Psychiatry ; 4: e343, 2014 Jan 14.
Article in English | MEDLINE | ID: mdl-24424389

ABSTRACT

Perceiving others in pain generally leads to empathic concern, consisting of both emotional and cognitive processes. Empathy deficits have been considered as an element contributing to social difficulties in individuals with autism spectrum disorders (ASD). Here, we used functional magnetic resonance imaging and short video clips of facial expressions of people experiencing pain to examine the neural substrates underlying the spontaneous empathic response to pain in autism. Thirty-eight adolescents and adults of normal intelligence diagnosed with ASD and 35 matched controls participated in the study. In contrast to general assumptions, we found no significant differences in brain activation between ASD individuals and controls during the perception of pain experienced by others. Both groups showed similar levels of activation in areas associated with pain sharing, evidencing the presence of emotional empathy and emotional contagion in participants with autism as well as in controls. Differences between groups could be observed at a more liberal statistical threshold, and revealed increased activations in areas involved in cognitive reappraisal in ASD participants compared with controls. Scores of emotional empathy were positively correlated with brain activation in areas involved in embodiment of pain in ASD group only. Our findings show that simulation mechanisms involved in emotional empathy are preserved in high-functioning individuals with autism, and suggest that increased reappraisal may have a role in their apparent lack of caring behavior.


Subject(s)
Cerebral Cortex/physiopathology , Child Development Disorders, Pervasive/physiopathology , Emotions/physiology , Facial Expression , Pain/psychology , Social Perception , Adolescent , Adult , Female , Functional Neuroimaging , Humans , Magnetic Resonance Imaging , Male , Young Adult
5.
Eur J Neurol ; 20(7): 1094-100, 2013 Jul.
Article in English | MEDLINE | ID: mdl-23560508

ABSTRACT

BACKGROUND AND PURPOSE: A cost of illness study was undertaken on behalf of the French Ministry of Health to estimate the annual cost of stroke in France with the goal of better understanding the current economic burden so that improved strategies for care may be developed. METHODS: Using primary data from exhaustive national databases and both top-down and bottom-up approaches, the stroke-related costs for healthcare, nursing care and lost productivity were estimated. RESULTS: The total healthcare cost of stroke patients in France in 2007 was €5.3 billion, 92% of which was borne by statutory health insurance. The average cost of incident cases was €16 686 per patient in the first year, while the annual cost of prevalent cases was a little less than half that amount (€8099). Nursing care costs were estimated at €2.4 billion. Lost productivity reached €255.9 million and that income loss for stroke patients was partially compensated by €63.3 million in social benefit payments. CONCLUSIONS: With healthcare costs representing 3% of total health expenditure in France, stroke constitutes an ongoing burden for the health system and overall economy. Nursing care added nearly half again the amount spent on healthcare, while productivity losses were more limited because nearly 80% of acute incident strokes were in patients over age 65. The high cost of illness underscores the need for improved prevention and interventions to limit the disabling effects of stroke.


Subject(s)
Cost of Illness , Stroke/economics , France/epidemiology , Health Care Costs , Humans , Incidence , Insurance, Health/economics , Nursing Care/statistics & numerical data , Prevalence , Stroke/epidemiology
6.
Rev Neurol (Paris) ; 169(2): 126-35, 2013 Feb.
Article in French | MEDLINE | ID: mdl-22749335

ABSTRACT

INTRODUCTION: This study evaluates comorbidities, primary and secondary drug prevention and two years survival among patients hospitalized for stroke during the first half of 2008. METHODS: First hospitalization with stroke diagnosis was identified by using the national hospital discharge database and linked to the reimbursement database of the beneficiaries covered by the general health insurance scheme (74% of the 64 million population). A medication was considered to be used when there were more than two reimbursements over the 6 months following or preceding hospitalization. RESULTS: Among the 36,844 patients with stroke, 31.6% had a main diagnosis of transient ischemic attack (TIA), 53.6% a cerebral infarct (CI) and 14.8% a cerebral hemorrhage (CH). For the 8429 patients aged less than 60 years, high frequency of low-income and full health insurance coverage (11% of the covered population) was found for CI (17.6%) and CH (24.6%). Specific refund for invalidating stroke before hospitalization was found for 16% of patients with CI and 10.5% of those with CH. During the two previous years, around 7% of all patients were hospitalized for stroke, 30% for arterial hypertension, 13% for cardiac electric disorders, 10% for coronary disease and 12% for diabetes. Death rates one month after hospitalization were 11.3% for CI and 33.8% for CH, and two years after 22.5% for CI, 43% for CH and 7.7% for TIA. At least one antihypertensive drug treatment was found for 55.2% of patients with a TIA before hospitalization and 62.9% after and respectively 59.4% and 65.8% for CI and 51.1% and 57.7% for CH. Before hospitalization, beta-blocker was the most frequent antihypertensive class (21 to 25.6% according to stroke type). After hospitalization, frequency increased for angiotensin-converting enzyme inhibitors among CI patients (31% vs. 18.7%) and calcium-channel blockers among CH patients (27.1% vs. 13.7%). Antiplatelet drugs were used by 58% of the patients with CI after hospitalization (27.8% before). An anticoagulant drug was present for 74.8% of patients with CI, 69.5% for TIA and 19.2% for CH. Among patients with ischemic stroke, half of them had a lipid-lowering drug after hospitalization. A combination of antihypertensive, anticoagulant and lipid lowering drugs was found for 32.9% of patients with a TIA, 39.9% for CI and 7.6% for CH after hospitalization. CONCLUSION: These patients presented frequently a history of stroke and comorbidities and their level of secondary prevention must be improved.


Subject(s)
Inpatients/statistics & numerical data , Stroke/epidemiology , Adult , Aged , Aged, 80 and over , Antihypertensive Agents/therapeutic use , Cardiovascular Agents/therapeutic use , Comorbidity , Drug Utilization/statistics & numerical data , Female , Fibrinolytic Agents/therapeutic use , France/epidemiology , Hospital Mortality , Hospitals, General , Humans , Hypoglycemic Agents/therapeutic use , Hypolipidemic Agents/therapeutic use , Kaplan-Meier Estimate , Male , Middle Aged , Patient Readmission/statistics & numerical data , Psychotropic Drugs/therapeutic use , Risk Factors , Secondary Prevention , Stroke/classification , Stroke/prevention & control , Young Adult
7.
Transl Psychiatry ; 2: e202, 2012 Dec 11.
Article in English | MEDLINE | ID: mdl-23233021

ABSTRACT

Gamma aminobutyric acid (GABA)-mediated synapses and the oscillations they orchestrate are altered in autism. GABA-acting benzodiazepines exert in some patients with autism paradoxical effects, raising the possibility that like in epilepsies, GABA excites neurons because of elevated intracellular concentrations of chloride. Following a successful pilot study,(1) we have now performed a double-blind clinical trial using the diuretic, chloride-importer antagonist bumetanide that reduces intracellular chloride reinforcing GABAergic inhibition. Sixty children with autism or Asperger syndrome (3-11 years old) received for 3 months placebo or bumetanide (1 mg daily), followed by 1-month wash out. Determination of the severity of autism was made with video films at day 0 (D0) and D90 by blind, independent evaluators. Bumetanide reduced significantly the Childhood Autism Rating Scale (CARS) (D90-D0; P<0.004 treated vs placebo), Clinical Global Impressions (P<0.017 treated vs placebo) and Autism Diagnostic Observation Schedule values when the most severe cases (CARS values above the mean ± s.d.; n=9) were removed (Wilcoxon test: P-value=0.031; Student's t-test: P-value=0.017). Side effects were restricted to an occasional mild hypokalaemia (3.0-3.5 mM l(-1) K(+)) that was treated with supplemental potassium. In a companion study, chronic bumetanide treatment significantly improved accuracy in facial emotional labelling, and increased brain activation in areas involved in social and emotional perception (Hadjikhani et al., submitted). Therefore, bumetanide is a promising novel therapeutic agent to treat autism. Larger trials are warranted to better determine the population best suited for this treatment.


Subject(s)
Autistic Disorder/drug therapy , Bumetanide/therapeutic use , GABA Modulators/therapeutic use , Asperger Syndrome/drug therapy , Autistic Disorder/diagnosis , Autistic Disorder/psychology , Child , Child, Preschool , Double-Blind Method , Female , Humans , Male , Severity of Illness Index , Treatment Outcome
8.
Encephale ; 37(1): 10-7, 2011 Feb.
Article in French | MEDLINE | ID: mdl-21349369

ABSTRACT

OBJECTIVE: The literature on autism reports regularly the presence of a peak of ability on the visuospatial tasks. The classic interpretation of this result refers to the theoretical model proposed by Frith (1989) who evokes a "lack of central coherence" in persons with autism that is a deficit in the mobilization of global processing. The research reported here has for objective to propose a reflection on the relevance of this model by asking the following question: is global processing impaired in autism or simply not mobilized for the benefit of the almost exclusive appeal to local treatment? METHODS: A group of children with high-functioning autism was compared with normally developping children (n=15 per group), matched on age and global level of intelligence. The clinical group, 14 boys and a girl, had received a diagnosis of typical autism according to the criteria of the ICD-10 (F84.0) confirmed by ADI-R. These children all used a functional language at the time of inclusion within the study, however all of them initially presented a delay in language (mean age: 8 years and 6 months; mean total IQ: 98.07). The typically developping group, 12 boys and three girls, were from ordinary school (mean age: 9 years, mean total IQ: 106.2). Two tasks were employed for the collection of data: the Wechsler Intelligence Scale for Children-Third Edition (WISC-III) was used to estimate the total-, verbal- and performance-IQ scores of every child and to match both groups. It also permitted the evaluation and comparison of the performances of the children on the following visuospatial tasks: "picture completion", "object assembly" and "block design". The NEPSY scale permitted the estimation and comparison of the levels of performance of both groups on visuospatial functions. RESULTS: In terms of scores, the tasks of the WISC-III, requiring visiospatial processing as well as the global evaluation of the visiospatial functions with the NEPSY, showed the absence of significant differences between children with high-functioning autism and typical children of the same age. However, differences of strategies appeared both between the groups and, in children with autism, according to the tasks to resolve. The comparison of subtests, "arrows" and "picture completion" on one hand, and "object assembly" and "block design" on the other, showed that children with autism are capable of mobilizing correct configural processing in the first ones but not in the second. The only factor which differentiates these tasks is the appeal or not to a motor coordination. It is possible that the lack of motor ease, often described in this type of children, sometimes leads them towards strategies of low level, i.e., to local adjustments, unlike the typical children who mobilize a strategy supported on a global representation of the purpose to be reached. CONCLUSION: If our results confirm the capacities of children with autism to resolve the tasks requiring a visiospatial processing, the strategies which they mobilize do not support the existence of a weakness of the central coherence. We suggest, in persons with autism, the idea of a priority granted to the local information treatment in the absence of a deficit of global or configural processing.


Subject(s)
Aptitude , Attention , Autistic Disorder/diagnosis , Autistic Disorder/psychology , Internal-External Control , Orientation , Perceptual Disorders/diagnosis , Perceptual Disorders/psychology , Psychomotor Performance , Visual Perception , Child , Female , Humans , Intelligence , Language Development Disorders/diagnosis , Language Development Disorders/psychology , Male , Problem Solving , Psychological Theory , Psychometrics/statistics & numerical data , Psychomotor Disorders/diagnosis , Psychomotor Disorders/psychology , Reference Values , Wechsler Scales/statistics & numerical data
9.
Arch Pediatr ; 17(8): 1243-8, 2010 Aug.
Article in French | MEDLINE | ID: mdl-20615674

ABSTRACT

The term "dyspraxia" was coined by Julian de Ajuriaguerra and Mira Stambak in 1964. This clinical term was treated very differently according to which explanatory model was adopted. Nowadays, it is used to refer to developmental coordination disorder in view of its neuro-developmental origin. In any case, the actual clinical situations vary and are often complex. In our opinion, it is first necessary to examine the differential diagnosis: apraxia in children caused by lesions, dysgraphia, simply delayed motor development, non-verbal learning disability syndrome, hemispheric specialisation deficits, pervasive developmental disorders (autisms, Asperger syndrome, atypical autism and other pervasive developmental disorders), mixed specific developmental disorders, multiple developmental disorder, and children with high potential. Next we focus on co-morbidity. Firstly, we look at psychopathological disorders associated with dyspraxia: autism and pervasive developmental disorders, dyscalculia/math disability, dyslexia/reading difficulties, dysphasia accompanied by verbal dyspraxia, intelligence deficiency, anxiety disorders, and attention-deficit hyperactivity disorder (ADHD). Secondly, we examine psychopathological disorders associated with dyspraxia. Children with developmental coordination disorder are less inclined to participate in collective games. As a result, there is a greater risk of them becoming lonely and isolated. They have higher child behaviour checklist (CBCL) scores in the somatic problems scale as well as for anxiety, depression and social withdrawal. They have low self-perception in sports as well as at school, which is related to their physical appearance and their self-esteem, attention deficit and externalized behaviour. These children are often at risk of academic failure and they suffer from oppositional defiant disorder and functional disorders. And finally, we believe that it is important to touch on the impact of these disorders on the family.


Subject(s)
Apraxias/psychology , Aphasia/etiology , Aphasia/psychology , Apraxias/classification , Apraxias/etiology , Child , Developmental Disabilities/classification , Developmental Disabilities/psychology , Family , Humans
11.
J Neuroradiol ; 31(4): 334-9, 2004 Sep.
Article in French | MEDLINE | ID: mdl-15545945

ABSTRACT

First, to summarize the results of teleradiology programs on neurosurgical emergency care in France. Second, to compare French data with the international literature. Third, to discuss the likely developments and future of teleneuroradiology and teleneurosurgery. Data on French use of telemedicine applications in neuroradiology come from a survey of telemedicine applications in France, which has been conducted in year 2003 at the request of the French ministry of the Research. Teleradiology clearly has a positive impact on emergency neurosurgical care by reducing the time to correct diagnosis and initiation of treatment of patients who need to be transferred and avoid unnecessary transfers. However, present teleradiology applications have organizational limitations that are summarized and discussed with reference to the literature. Further developments in information and communications technology have the potential to revolutionise neurosurgical emergency care and contribute to improve the training of neuroradiology and neurosurgery staff.


Subject(s)
Emergency Treatment/methods , Neuroradiography/methods , Teleradiology/organization & administration , Diffusion of Innovation , Emergencies , Emergency Treatment/standards , Forecasting , France , Health Services Research , Humans , Needs Assessment , Neuroradiography/standards , Neurosurgery/organization & administration , Patient Transfer , Program Evaluation , Time Factors
12.
Nucl Med Commun ; 24(12): 1215-24, 2003 Dec.
Article in English | MEDLINE | ID: mdl-14627847

ABSTRACT

We prospectively compared the impact of the standard approach, of fluorodeoxyglucose positron emission tomography (FDG PET) and of FDG dual-head coincidence gamma camera imaging (DHC) in preoperative staging of patients with non-small-cell lung cancer (NSCLC). In addition to traditional staging, 42 patients were studied with a PET system and a DHC system. The number of lesions detected on DHC and on PET were compared independently of the proof of a tumoural invasion. Then, for the sub-group of lesions with the proof of a tumoural invasion, the sensitivity of the different imaging modalities was compared. Finally, stagings were compared with final staging established by histopathological findings (n=28), additional imaging modalities (n=4), clinical and traditional imaging follow-up over at least 4 months. DHC detected 105 of the 145 lesions considered as pathological on PET (73%, P=0.01), with a concurrence of 89% (NS) in lesions larger than 1.5 cm, and only 17% (P=0.03) in those smaller or equal to 1 cm. Traditional staging detected 87 of the 114 verified tumoural lesions (76%), PET 110/114 (96%, P=0.01 vs traditional staging), DHC 88/114 (77%, NS vs traditional staging, P=0.01 vs PET). PET correctly predicted the N stage in 39/42 (93%) patients, DHC in 38/42 (90%), and computed tomography in 32/42 (76%). PET correctly predicted the M stage in 42/42 (100%) patients, DHC in 41/42 (98%), and traditional staging in 38/42 (90%). Identical NM staging was obtained with DHC and PET in 38/42 (90%) patients. Compared to traditional NM staging, PET correctly up-staged 9/42 (21%) patients and down-staged 3/42 (7%), with one additional false N up-staging. DHC correctly up-staged 7/42 (17%) patients and down-staged 3/42 (7%), with one additional false N down-staging. PET correctly reclassified 4/42 (9.5%) patients from resectable to unresectable and incorrectly reclassified one. DHC correctly reclassified 3/42 (7%) patients without false therapeutic reclassification. Although DHC detected fewer lesions than PET, DHC is a possible alternative to PET since the impact on staging was high as compared with traditional staging and was very similar to that of PET.


Subject(s)
Carcinoma, Non-Small-Cell Lung/diagnostic imaging , Fluorodeoxyglucose F18 , Gamma Cameras , Lung Neoplasms/diagnostic imaging , Tomography, Emission-Computed/methods , Adult , Aged , Aged, 80 and over , Carcinoma, Non-Small-Cell Lung/pathology , False Negative Reactions , False Positive Reactions , Female , Humans , Lung Neoplasms/pathology , Male , Middle Aged , Neoplasm Staging/methods , Preoperative Care/methods , Radionuclide Imaging/methods , Radiopharmaceuticals , Reproducibility of Results , Sensitivity and Specificity , Tomography, Emission-Computed/instrumentation
13.
Ann Cardiol Angeiol (Paris) ; 52(3): 162-8, 2003 Jun.
Article in French | MEDLINE | ID: mdl-12938568

ABSTRACT

Intracoronary brachytherapy aims at a reduction of in-stent restenosis by lessening neo-intimal proliferation. To assess its clinical potential, a systematic review of the literature indexed in the standard biomedical bibliographic databases selected eight prospective randomized clinical trials; seven of them, comparing coronary brachytherapy and non-treatment or placebo, have been included in the present meta-analysis. This analysis confirms the angiographic benefit of this procedure, as reported in the individual studies; it also shows, however an excess of clinical adverse effects not exhibited by any individual trial. Therefore, intracoronary brachytherapy cannot be recommended as routine practice, while one cannot rule out its interest in special situations.


Subject(s)
Angioplasty, Balloon, Coronary , Brachytherapy , Coronary Restenosis/prevention & control , Stents , Brachytherapy/adverse effects , Coronary Angiography , Coronary Restenosis/diagnostic imaging , Data Interpretation, Statistical , Follow-Up Studies , Humans , Placebos , Prospective Studies , Randomized Controlled Trials as Topic , Time Factors
14.
Presse Med ; 29(33): 1833-41, 2000 Nov 04.
Article in French | MEDLINE | ID: mdl-11109441

ABSTRACT

UNLABELLED: ALTERNATIVE TO SURGERY: New stereotactic guided breast biopsy procedures may constitute a major issue for the diagnosis of non-palpable breast lesions detected at mammography by eliminating the need for surgery in many women with benign breast disease. INDICATIONS: Vacuum-assisted core biopsies provide more complete sampling than the conventional 14-gauge stereo-tactic core biopsies, reducing the number of unsatisfactory biopsies. The more invasive advanced breast biopsy device obtains an intact lesion in its entirety for histological assessment. Currently, there is no definite strategy delineating the precise indications for the diagnosis of screening detected abnormalities. PERSPECTIVES: Because of the increase of the diagnostic armamentarium, care of women with non-palpable breast lesions should be multidisciplinary, involving radiologist, surgeons and histologists and rigorous medical and economic evaluation of diagnostic strategies involving these new health technologies should be pursued.


Subject(s)
Breast Neoplasms/pathology , Mammography , Biopsy, Needle , Breast/pathology , Female , Humans , Predictive Value of Tests
15.
Ann Med Interne (Paris) ; 151 Suppl 1: 1S5-12, 2000 May.
Article in French | MEDLINE | ID: mdl-10896982

ABSTRACT

In 1991 the public hospitals in Paris set up a plan to regulate the prescription of IVIg. The plan includes an expert committee and reliable data collection. The expert committee has a threefold mission: i) perform an annual up-date of IVIg classification using three categories: accepted indications (group I), currently deabated indications (group II), and unwarranted indications (group III); ii) develop guidelines for improved therapeutic strategies; iii) stimulate research. Data on use of IVIg are collected in 16 pilot hospitals. These data designate IVIg prescriptions by indication. Data are centralized by the CEDIT which publishes an annual report. Between 1988 and 1991, prescription of IVIg increased at an average annual rate of 33%. Between 1991 and 1996, the amount of IVIg used leveled off: approximately 330 kilograms/year, excluding research protocols. In 1997 there was a decline to 299 kilograms accounting for a total expenditure of 44 million French francs (US$ 6.7M). In 1997, group I prescriptions represented 80% of all IVIg prescriptions, group II 9.8% and group III 9.1%. Comparison of medical practice with a scientificaly recognised reference made it possible for AP-HP to set up an effective regulation of IVIg prescriptions. The longevity of this evaluation work is by itself a success.


Subject(s)
Immunoglobulins, Intravenous/therapeutic use , Data Collection , Drug Costs/statistics & numerical data , Drug Prescriptions/economics , Drug Prescriptions/statistics & numerical data , Drug Utilization/statistics & numerical data , France/epidemiology , Health Expenditures/statistics & numerical data , Hospitals, Public/statistics & numerical data , Humans , Immunoglobulins, Intravenous/economics , Paris/epidemiology , Pilot Projects , Practice Guidelines as Topic , Practice Patterns, Physicians'/statistics & numerical data , Research
16.
Melanoma Res ; 8(5): 431-7, 1998 Oct.
Article in English | MEDLINE | ID: mdl-9835457

ABSTRACT

Digital epiluminescence microscopy (DELM) is currently being developed for the diagnosis of pigmented skin lesions (PSL) and the early diagnosis of malignant melanoma. So far there are only few studies documenting if modifications in PSL may be detected by DELM over time. Our purpose was to determine if DELM is an adequate tool for the follow-up of PSL and if any detectable modifications occur within PSL over time. We followed 150 PSL over 2 years in 67 patients using a DELM system. At the end of the follow-up period, the retrieved DELM images were analysed by two observers and evaluated for the presence and type of modifications. Modifications were observed in 69% of the PSL. These modifications were of two types. Type 1 corresponded to an increase in the pigment content of the lesion without modification of either its size or architecture, and was probably related to sun-related seasonal variation. Type 2 included an increase in the size and various variations in the architecture, corresponding to a progression of the lesion. Correlation of the type of modification with the type of PSL, as defined by its epiluminescence microscopy (ELM) patterns, indicated that type 2 modifications were associated with lesions initially showing ELM signs of 'dysplasia', whereas lesions showing only type 1 modifications did not show such patterns. We have documented the feasibility of following up PSL with DELM. The pattern of modification of a PSL over time could be correlated with its nature.


Subject(s)
Melanocytes/pathology , Melanoma/pathology , Nevus, Pigmented/pathology , Skin Neoplasms/pathology , Adolescent , Adult , Female , Follow-Up Studies , Humans , Image Processing, Computer-Assisted , Luminescent Measurements , Male , Melanoma/diagnosis , Microscopy/methods , Nevus, Pigmented/diagnosis , Skin Neoplasms/diagnosis
17.
Pediatr Radiol ; 28(7): 557-61, 1998 Jul.
Article in English | MEDLINE | ID: mdl-9662585

ABSTRACT

BACKGROUND: A new low-dose digital X-ray device, based on Charpak's Nobel prize-winning multiwire chamber, enables the production of images at very low doses. Objectives. To present the first dosimetric and clinical results. MATERIALS AND METHODS: The analysis was performed on 93 children with scoliosis and 47 undergoing pelvic radiography. The comparative study between conventional X-ray and the new technique focused on three points: (1) the dose delivered by each system (2) the diagnostic information provided by each system and (3) comparison of image quality criteria with European guidelines. RESULTS: The mean ratio of conventional dose to that of the low-dose technique was 13.1 for the spinal examination and 18.8 for the pelvis. There was no significant difference in diagnostic information available from each modality, but there was a slight difference in quality criteria in favour of the conventional technique. CONCLUSION: This new device allows spectacular dose reduction, consistent with adequate clinical information. Improvements of the prototype will lead to extension of potential indications and industrial development.


Subject(s)
Radiographic Image Enhancement/instrumentation , Child , Child, Preschool , Humans , Pelvic Bones/diagnostic imaging , Radiation Dosage , Scoliosis/diagnostic imaging
18.
Dermatology ; 195(2): 108-11, 1997.
Article in English | MEDLINE | ID: mdl-9310714

ABSTRACT

BACKGROUND: In vivo epiluminescent light microscopy (ELM) of pigmented skin lesions reveals numerous elementary structures. Among them, the pigment network (PN), black dots (BD) and brown globules (BG) constitute important semiologic features. Based on histological extrapolations, it has been postulated that PN should reflect the presence of melanin in the epidermis and its honeycomb aspect should result from the dermoepidermal architecture. OBJECTIVE: To demonstrate this directly by analyzing separately by ELM the epidermal and dermal sides of melanocytic lesions. METHODS: We split the epidermis from the dermis of 10 pigmented lesions (6 lentigos, 4 nevocytic nevi) by incubation with dispase. ELM images were done in vivo before excision, then ex vivo on the whole specimen and separately on the split epidermis and dermis. Epidermal and dermal specimens were finally controlled by histology. RESULTS: PN was observed only on the epidermal side of the split. Its organization was remarkably conserved after the procedure as compared with prior in vivo images. In contrast, pigmentation observed on dermal sides of the splits showed no organized pattern and corresponded to melanophages. BG were found on the dermal side and BD on the epidermal side of the split lesions, which confirms previous hypotheses. CONCLUSION: By subtracting the dermal pigmentation and vessels from the image, the split technique has thus established the epidermal origin of the PN and given a more detailed ELM analysis of network components.


Subject(s)
Lentigo/pathology , Microscopy, Fluorescence/methods , Nevus, Pigmented/pathology , Skin Neoplasms/pathology , Skin/pathology , Culture Techniques , Diagnosis, Differential , Epidermal Cells , Epidermis/pathology , Humans , Melanocytes/pathology , Sensitivity and Specificity
19.
Dermatology ; 195(1): 84-5, 1997.
Article in English | MEDLINE | ID: mdl-9267752

ABSTRACT

BACKGROUND: Treatment by ultraviolet radiation (UV) during human immunodeficiency virus (HIV) infection is controversial, since exposure of HIV-infected cells in vitro to UV enhances HIV replication in vitro. METHODS: Four consecutive AIDS patients with psoriasis and CD4 count lower than 20/mm3 were treated with 8-methoxypsoralen and UVA (PUVA). HIV viremia expressed as long of HIV-1 RNA copies/ml of plasma was quantified 10 min before and 1 h following UVA exposure, every week during PUVA therapy and at the end of treatment. The Psoriasis Area Surface Index (PASI) score was used to quantify the severity of psoriasis. RESULTS: No significant change in HIV-1 RNA level was observed in the 18 paired samples analyzed before and 1 h after PUVA (median: -0.05 log HIV-1 RNA, range: -0.50-0.21, p = 0.10). After 12-31 UVA exposure for a total dose of 15.5-196 J/cm2 over a period of 6-15 weeks, viremia changes from baseline in the 4 patients were -0.61, -0.07, 0.36 and 0.39 log HIV RNA. In 1 patient without antiviral treatment, a persistent decrease in viremia and transient increase in CD4 cell count were observed. PUVA was well tolerated and associated with significant improvement of the PASI score in 3 patients. CONCLUSION: HIV viremia is not significantly modified by PUVA therapy in AIDS patients with psoriasis.


Subject(s)
Acquired Immunodeficiency Syndrome/virology , PUVA Therapy , Viremia/virology , Anti-HIV Agents/therapeutic use , CD4 Lymphocyte Count , HIV-1/genetics , HIV-1/isolation & purification , HIV-1/radiation effects , Humans , Methoxsalen/therapeutic use , Pilot Projects , Psoriasis/drug therapy , RNA, Viral/analysis , Radiation Dosage , Time Factors , Ultraviolet Rays , Virus Replication/radiation effects
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