Les inhibiteurs spécifiques de la recapture de la sérotonine dans la dépression de l’enfant et de l’adolescent: revue des controverses récentes

European and US drug regulatory authorities have recently warned against the use of selective serotonin reuptake inhibitors (SSRIs) in childhood and adolescent depression. Through an extensive literature review on the use of SSRIs to treat depression in children and adolescents — including psychiatric clinical trials, pharmacology, and drug safety data — we will: i) describe the main arguments justifying various regulatory decisions; ii) present published data and subsequent meta-analyses; iii) discuss how to integrate the recommendations into daily clinical practice, freeing professionals from a Manichean approach. We reach the limits of evidence-based medicine, which provide the basis of the scientific work of the regulatory authorities.     

Application de la technique de PCR en temps réel à l’étude de l’ADN ancien

Real-time Polymerase Chain Reaction (PCR) for the study of ancient DNA. The properties of ancient DNA (aDNA) make difficult the retrieval of DNA sequence. The advantage of Real-Time PCR was exploited, for the first time, in the study of aDNA. We determined the optimal condition to amplify, in one round of PCR, aDNA, which should be directly sequenced. Beside the verification of aDNA authenticity, we compared two cleaning bone methods: scalpel and ethanol. The ethanol specimens showed the best DNA yield. The aDNA was extracted and amplified (mitochondrial hypervariable region I) from five skeletons exhumed from the archaeological site of Notre-Dame-du-Bourg (France), dated from 3rd to 17th century. To cite this article: R. Kefi et al., C. R. Palevol 2 (2003) 125–132.     

Le Paléolithique supérieur de la région centre de l’île de Honshû

Tokai area is situated in the middle of Japan and has various configurations of ground. The eastern area has thick natural layers with volcanic ash which has been supplied from Mt. Fuji. About five chronological stages of Paleolithic culture from trapeze and edge-ground axe culture to microlith culture through backed blade culture have been found in the layers. These stages of Paleolithic culture are indicators of chronological studies in Tokai area. On the other hand, it is difficult to advance chronological studies in the middle east, middle, and west areas, because they have little thickness of layers with volcanic ash. However, different Paleolithic artifacts are found in top and bottom layers which put the AT layer between at Tsubakibora Site in Gifu Prefecture, and they have helped very much chronological studies of Paleolithic culture in the west area. Here is the first result of Paleolithic studies in Tokai area with artifacts which have been found on the forth layer of scoriae at Idemaruyama Site are dated about 35,000 years, one of the oldest Paleolithic culture in Japan. In addition, some lines of pits which were dated 30,000 years were found at Hatsunegahara Site, and they provided valuable data to study Paleolithic hunting. Finally, a holed pendant which had 10 notches on one side was unearthed from Fujiishi Site, and it was dated 19,000 years ago. At Terada and Hino Site, a flat big stone which had carvings was found, though the shape and use were seemed to be different from the pendant at Fujiishi Site.     

Quelques considérations sur l'enseignement de la médecine physique et de la réhabilitation

Particularly since World War II physical medicine and rehabilitation have assumed a growing importance. The efforts of the Canadian Association of Physical Medicine and Rehabilitation, following a survey of Canadian universities, to increase the theoretical and practical teaching of physiatrics are emphasized. It is considered important that the teaching of physical medicine and rehabilitation should be carried out concurrently with other medical and surgical teaching programs. Paramedical and auxiliary rehabilitation personnel should participate in the teaching program. The number of hours devoted to physiatrics should be increased, and the medical student should be permitted to choose physical medicine and rehabilitation as a part of his internship program.     

Intérêt d’une semi-quantification et d’une analyse statistique automatique pour l’interprétation de la tomoscintigraphie cérébrale de perfusion dans la maladie d’Alzheimer

IntroductionAs the visual interpretation of the brain perfusion SPECT for the diagnosis of Alzheimer's disease might be difficult, it is wished to benefit from techniques allowing to improve the diagnostic accuracy especially for the inexperienced readers.Materials and methodsThree readers retrospectively interpreted 77 ^99mTc-ECD SPECT studies within the context of suspected neurodegenerative disease. The probability of Alzheimer's disease was quoted from 1 to 5, and the optimum sensitivity and specificity values were determined from ROC curves. The readers also attributed a hypoperfusion score to 13 brain regions; a diagnosis was obtained from this semi-quantification using a simple logic rule. The SPECT scans were also analyzed using the Planet Neuro software and a diagnosis was reached from a threshold for 2 of the 90 analyzed regions. The gold standard was established by a comprehensive neurological evaluation with at least 5 years of follow-up.ResultsThe sensitivities and specificities of the three readers were 50 %, 56 %, 28 % and 76 %, 83 % and 90 %, respectively. Using the semi-quantification they were 50 %, 67 %, 61 % and 54 %, 85 %, 69 %. The results of two readers were more in agreement. Using the automatic quantification, sensitivity was 78 % and specificity 81 %.ConclusionThe semi-quantification seems to ameliorate the results of and the agreement between certain readers. However, the automatic quantification seems to be the only way of assisting all of the readers to improve their diagnostic performances.     

Intérêt de l’utilisation de la scintigraphie osseuse dans le diagnostic et le suivi de l’ostéochondrite primitive de la hanche

Osteochondritis, or Legg-Calvé-Perthes disease (LCP), is a necrosis of the proximal femoral epiphysis. This vascular accident entails on the complex phenomenon of growth of the child's hip and can result in deformations or even a strict destruction of the proximal femoral epiphysis. The aim of this article is to show the interest of the bone scintigraphy (BS) in precocious diagnosis and follow-up of LCP disease. In this aim, we introduced a clinical case of LCP disease where BS allowed a precocious diagnosis and a strigent monitoring. Discussion of case includes a systematic review of literature.     

Intérêt de la scintigraphie rénale au DMSA dans les pyélonéphrites aiguës de l’enfant

IntroductionAcute pyelonephritis is responsible for significant morbidity during the acute phase and distant irreversible kidney damage. However, diagnosis is often difficult in children. The aim of our study was to evaluate in children hospitalized for suspected acute pyelonephritis prevalence of acute lesions revealed by scintigraphy with ^99mTc labeled dimercaptosuccinic acid (DMSA) and the relationship between renal parenchymal lesions and different clinical factors and biological risks.MethodsThis is a prospective study collecting 40 children admitted with suspected infection of the high urinary tract. All have benefited from DMSA renal scintigraphy.ResultsThe average age of our patients was 3.25 years. The DMSA scan showed signs of acute pyelonephritis in 32.5% of cases. Taking this examination as a reference, fever was the most sensitive clinical signs (76.9%), but the specificity was only 48.1%. CRP (≥ 20 mg/mL) was the most sensitive (92.3%) but with a specificity of 40.7% organic signs. A high CRP was associated with acute pyelonephritis significantly (P = 0.0033). Sixty-three percent of refluxing kidneys were associated with acute pyelonephritis versus 20.8% of non-refluxing kidneys, with a significant difference (P = 0.007).ConclusionIn case of urinary tract infection in children, a complete clinical and laboratory table may be sufficient to retain the diagnosis of acute pyelonephritis. However, this possibility is rare. In the opposite case, a DMSA scan should be performed to confirm the diagnosis.     

A propos de l'intervention des aéroions dans les processus de régulation de la lipémie et de la cholestérolémie

Resume Les expériences ont porté sur des lapins repartis en deux groupes parallèles — un groupe étant traité avec des aéroions négatifs en concentrations moderées (n^– = 10 – 40.000; n⁺ = 1.000) et l'autre sans aéroionothérapie (témoins). Par rapport aux animaux témoins (pas exposés aux aéroions),on a enregistré,sous l'influence de l'aéroionothérapie, que: (1)il y a une tendence de normalisation de la motilité spontanée, deprimée par une alimentation contenant un excès de cholestérol(0,3 g/kg/jour); (2) la lipémie et la cholestérolémie sont restées à un niveau plus bas chez les animaux alimentés au cholestérol; (3) la lipémie et la cholestérolémie, de même que l'iode thyroïdien, sont restées aux valeurs voisines de celles normales,chez les animaux nourris avec un excès (20 mg/kg/jour), de substances antithyroïdiennes naturelles (provenant du chou).

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Groups of rabbits were exposed to negative air ions of moderate concentrations (n^– = 10 – 40,000; n⁺ = 1,000) while others served as controls. (1) When rabbits were fed a cholesterol-rich diet (0.3 g/kg/day)causing reduction of motility in the control animals, their motility was normalized under air ion treatment. (2) The blood cholesterol and lipid levels of rabbits on a cholesterol-rich diet were lower with air ion treatment than in controls.(3) When rabbits were fed a diet with thyroid blocking agents from cabbage the blood cholesterol and lipid levels and the thyroid iodine content remained unchanged with air ion treatment.

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Zusammenfassung Gruppen Kaninchen wurden mit negativen Luftionen in mässigen Konzentrationen (n^– = 100 000 – 40 000; n⁺ = 1 000) behandelt, während andere als Kontrollen dienten. (1) Die durch Fütterung von cholesterinreicher Diät (0,3 g/kg/Tag) verminderte Motilität der Tiere wurde unter der Luftionenbehandlung normalisiert. (2) Der durch Fütterung von cholesterinreicher Diät erhöhte Blutcholesterin- und-fettspiegel fiel durch Luftionenbehandlung ab. (3) Der durch Fütterung von strumipriven Substanzen aus Kohl erhöhte Cholesterin- und Fettspiegel im Blut und verminderte Jodgehalt der Schilddrüse wurde durch Luftionenbehandlung nicht beeinflusst.

     

Intérêt de la ponction épididymaire et de la biopsie testiculaire systématique dans la prise en charge de l’azoospermie obstructive

Introduction

In obstructive azoospermia (OA), even if spermatozoa recovery rate are high, pregnancy rates could be lower as expected. When almost surgeons stop if they could find motile spermatozoa in the epididymis after microsurgical epididymal sperm aspiration (MESA), in our center, we add systematically a testicular biopsy with testicular sperm extraction (TESE). What are our sperm extraction rates in MESA or TESE? Are pregnancy and miscarriage rates different regarding the sperm origin?

Material and methods

A retrospective study including 48 infertile couples with ICSI because of OA. Between 2003 and 2011, each patient had a complete aetiological exploration and a surgery with the association of MESA and TESE. ICSI were asynchronous. Each time it was possible, ICSI was realized first with epididymal spermatozoa.

Results

For 48 couples, 99 ICSI were realized. Fifteen couples had 24 ICSI-TESE because no spermatozoon was found in MESA. Eleven couples had 20 ICSI-TESE because of bad quality of sperm recovered with MESA. Twenty-two couples had 22 ICSI-MESA in first intention. If failed, 11 couples had continued with 12 ICSI-MESA and 10 with 20 ICSI-TESE. Although the number of injected oocytes (7,1±4,1 vs 6,9 ±3,6 P: 0,8) and embryos (4,5±3,0 vs 4,7±2,7; P: 0,7) were not significantly different in the two ICSI groups, the number of top quality embryos (2,4±1,9 vs 3,6±2,0 P: 0,005) and frozen embryos (0,9±1,8 vs 1,7±1,9 P: 0,04) were higher in the ICSI-TESE group. Pregnancy rate per punction (58,5% vs 26,5%, P: 0,002) was higher when testicular spermatozoa were used.

Conclusion

Our approach is original with the systematic association of MESA and TESE for each OA man, when others stop surgery when they can find spermatozoa with MESA. We found that more than the half of epididymal explorations were not useful because negative or of bad quality. Embryo quality and per punction pregnancy rate were better with testicular spermatozoa. Association of MESA and TESE could improve the management of these infertile men without exposing them to an over surgical risk.     

Évaluation de la TEP au 18F-FDG dans l’exploration de la récidive des carcinomes colorectaux

PurposeThe aim of the study was to evaluate the diagnostic performance, the prognosis factors and the therapeutic impact of 18F-FDG positron emission tomography (FDG-PET) in the detection of recurrent colorectal cancers.MethodsSixty PET/CT with 18F-FDG and CT were performed in 52 patients, at the Paul Papin cancer center between 2003 and 2005, following suspicion of colorectal cancer relapse. The FDG-PET impact on the clinical management was studied by examination of multidisciplinary concertations results. Survival analysis were realized with a mean follow up of 2.2 years.ResultsRecurrence was confirmed for 50 explorations by histologic (n = 32), radiologic (n = 14) or clinical (n = 4) findings. Twenty patients died during the time of the study. On a patient based analysis, FDG-PET sensitivity, specificity and overall accuracy were 90, 90, 90% respectively compared with 74, 50 and 70% for CT. FDG-PET changed the clinical management in 18 cases (30%). A positive FDG-PET signal, more than one hepatic lesion, more than two lymph node lesions detected on FDG-PET and more than two hepatic lesions on CT were characterized as bad prognostic factors for survival. Multivariate analysis showed that the only independent bad prognostic factor was the FDG-PET detection of more than two liver lesions.ConclusionThese results confirmed the important impact of FDG-PET in the clinical management of patients with a suspected recurrence of colorectal cancer.     

La paléoflore autuno-stéphanienne de la région de Demnate(Est de Marrakech-Maroc)

The paleoflora described and pictured in this paper has been collected in two deposits of the area of Demnate: the OT6 bis drilling in the oriental Haouz and an exposure in the Rhojdamas (High-Atlas). Two completely different associations have been characterized: one hygrophilous and autochtonous of the «Stephanian type and the other mesoxerophilous and allochtonous (vegetation of the upland?) of the «Autunian type. In the OT6 bis drilling, the two floras alternate so that it is impossible to draw a precise boundary between the Stephanian and Autunian. In the Rhojdamas, only the Autunian flora has been identified. Such a combination of the two floras has similarly been recorded in several stephanian basins of the French Massif Central.     

Intérêt de l’introduction à la nomenclature du test de détection des HPV

Le cancer du col de l’utérus reste un problème de santé publique puisque 900 000 nouveaux cas sont diagnostiqués chaque année de par le monde [Luthra] et il est responsable en France de plus de 1600 décès par an. Pourtant, depuis plus de 40 ans, le dépistage de masse des précurseurs du cancer invasif est tout à fait réalisable et le traitement des anomalies cervicales pré-invasives amène généralement à la guérison.     

Intérêt de l’interprétation collégiale de l’échographie cervicale,de la scintigraphie 99mTc-MIBI et de la TEP-TDM à la 18-Fluorocholine dans l’hyperparathyroïdie primaire : expérience du service de médecine nucléaire de l’hôpital Cochin

ObjectivesThis study aims to assess performances of preoperative conventional imaging (99mTc-MIBI scintigraphy, cervical Ultrasonography) and 18F-fluorocholine PET/CT (FCH PET/CT) exams in the detection of hyperfunctioning parathyroid gland(s) in patients operated from primary hyperparathyroidism (pHPT).MethodsBefore surgery, 51 consecutive patients with biochemically confirmed pHPT had successively cervical ultrasonography (cUS), 99mTc-MIBI scintigraphy and FCH PET/CT, all performed in the same Nuclear Medicine Department. 99mTc-MIBI scintigraphy were performed immediatly after cUS and interpreted by same operators. FCH PET/CT exam were interpreted independently by two nuclear medicine physicians. An additional interpretation session integrating the three imaging modalities read in consensus as a combined imaging set was performed.ResultsAt surgery, 69 lesions were removed: 32 parathyroid adenoma and 37 parathyroid hyperplasia. 70% of patients had single-gland disease and 30% had multiglandular disease at histopathology analysis. In the patient-based analysis, sensitivity and accuracy in the detection of single gland disease) for FCH PET/CT, cUS and for 99mTc-MIBI scintigraphy were 86% [0.71–0.94] and 86% [0.70–0.95], 69% [0.52–0.81] and 69% [0.51–0.83], 40% [0.26–0.56] and 40% [0.24–0.58], respectively. Sensitivity and accuracy of the combined imaging set for the detection of single gland disease were 94% [0.81–0.99] and 94% [0.81–0.99].ConclusionOur results suggest that cUS/99mTc-MIBI scintigraphy and FCH PET/CT interpreted during a comprehensive session could be the ideal practice to precisely localize parathyroid lesion(s) in patients with pHPT before surgery.     

Intérêt de la tomoscintigraphie cardiaque à la 123I-mIBG couplée à la perfusion myocardique dans le diagnostic de l’atrophie multisystématisée

ObjectiveThe aim of this prospective study is to assess the pertinence of using ¹²³I-mIBG myocardial tomoscintigraphy coupled with perfusion scintigraphy as a diagnostic tool, to discriminate between multiple system atrophy (MSA) and idiopathic Parkinson's disease (PD) at first guided by clinical data and L-DOPA tests.Material and methodsForty patients, aged from 43 to 78 years (median 62 years) with Parkinson's syndrome were studied. Nineteen had a diagnosis of PD (criteria of brain bank) and 21 AMS (Gibbs criteria). All were given test to acute L-DOPA. Chest-centered planar imaging (128 × 128 matrix, 5 minutes of duration) is performed at 1 hour and 4 hours after injection of 220 MBq of ¹²³I-mIBG, in addition a non-synchronised tomoscintigraphy (64 × 64 matrix, 32 images of 50 seconds , zoom 1.45) was performed after the 4th hour and 15 minutes after injection of 200 to 400 MBq of ^99mTc-tetrofosmin. Besides neurological data, the parameters retained for comparison purposes with ¹²³I-mIBG cardiac tomoscintigraphy were patients’ age, duration of disease and L-DOPA test results. Two regions of interest (ROI) identical in size and in shape are used for ¹²³I-mIBG uptake quantifications (H/M and washout [Wo]). The first one was placed in projection of mediastinum (M) and the other one in projection of heart (H).ResultsWe found an overall decreased uptake of the myocardial ¹²³I-mIBG without perfusion abnormality in 15 of 19 patients with PD and 11 among them were L-DOPA sensitive (L-DOPA test greater than 30%). Normal tracer uptake with ¹²³I-mIBG associated with an almost quite normal perfusion was seen in 15 of 21 patients with MSA and they were little or not L-DOPA sensitive (L-DOPA test less than 30%). Therefore, 10 discordant cases (25%) between cardiac scintigraphy and clinical evolution of disease with also discordant L-DOPA tests were observed. In the PD group, quantification of data enhanced the diagnostic decision with low heart to mediastinum ratio (H/M) (1.32 ± 0.15 at the early stage and 1.25 ± 0.13 at the later stage). In the MSA group, the uptake of ¹²³I-mIBG (1.66 ± 0.43 at the early stage and 1.72 ± 0.42 at the later stage) was comparable to literature data, however, with significant inter-individual variations. The association of data of scintigraphy with L-DOPA test allows to improve sensitivity in 84% and specificity in 90.5%.ConclusionOur prospective study of 40 cases shows the relevance of cardiac sympathetic postganglionic imaging with ¹²³I-mIBG coupled with myocardial perfusion scintigraphy to discriminate between MSA and PD with a higher sensitivity (71.4%) compared to the test with L-DOPA but a lower specificity (78.9%) than the L-DOPA. The difficulty of diagnosis is firstly linked to damage occurring to both the pre- and postganglionic sympathetic systems in patients with MSA and secondly to the integrity of the sympathetic nerve endings in patients with PD. However, the association of data of scintigraphy with L-DOPA test show a significant improvement of sensibility (84%).     

Cytochrome P450 et activation génétique — de la pharmacologie à l’élimination du cholestérol et à la régression de l’athérosclérose

Background

Lipoproteins are closely associated with the atherosclerotic vascular process. Elevated levels of highdensity lipoprotein cholesterol (HDL-C) and apolipoprotein AI (apo AI) in plasma indicate a low probability of coronary heart disease (CHD) together with enhanced longevity, and elevated levels of low-density lipoproteincholesterol (LDL-C) and apo B indicate an increased risk of CHD and death. Studies linking gene activation and the induction of cytochrome P450 with elevated plasma levels of apo AI and HDL-C and lowered plasma levels of LDL-C presented a new potential approach to prevent and treat atherosclerotic disease.

Objective and methods

This is a review aimed at clarifying the effects of P450-enzymes and gene activation on cholesterol homeostasis, the atherosclerotic vascular process, prevention and regression of atherosclerosis and the manifestation of atherosclerotic disease, particularly CHD, the leading cause of death in the world.

Results

P450-enzymes maintain cellular cholesterol homeostasis. They respond to cholesterol accumulation by enhancing the generation of hydroxycholesterols (oxysterols) and activating cholesterol-eliminating mechanisms. The CYP7A1, CYP27A1, CYP46A1 and CYP3A4 enzymes generate major oxysterols that enter the circulation. The oxysterols activate — via nuclear receptors — ATP-binding cassette (ABC) A1 and other genes, leading to the elimination of excess cholesterol and protecting arteries from atherosclerosis. Several drugs and nonpharmacologic compounds are ligands for the liver X receptor, pregnane X receptor and other receptors, activate P450 and other genes involved in cholesterol elimination, prevent or regress atherosclerosis and reduce cardiovascular events.

Conclusions

P450-enzymes are essential in the physiological maintenance of cholesterol balance. They activate mechanisms which eliminate excess cholesterol and counteract the atherosclerotic process. Several drugs and nonpharmacologic compounds induce P450 and other genes, prevent or regress atherosclerosis and reduce the occurrence of non-fatal and fatal CHD and other atherosclerotic diseases.     

Apport de la TEP/TDM au 18FDG dans la stadification initiale et l’évaluation précoce de la réponse thérapeutique des rhabdomyosarcomes pédiatriques

PurposeThe objective of this study was to retrospectively evaluate the impact of positron emission tomography/computed tomography (PET/CT) using fluorine-18-fluorodeoxyglucose (FDG), in comparison with conventional imaging modalities (CIM), for initial staging and early therapy assessment in paediatric rhabdomyosarcoma.Patients and methodsPrior to treatment, 18 patients (age range, 9 months to 18 years) with histologically proven rhabdomyosarcoma underwent FDG PET/CT in addition to CIM (magnetic resonance imaging of primary site, whole body CT and bone scintigraphy). After three courses of chemotherapy, 12 patients underwent FDG PET/CT in addition to CIM. RECIST criteria and visual analysis of FDG uptake were used for assessment of response. The standard of reference was determined by an interdisciplinary tumor board based on imaging material, histopathology and follow-up data (median = 5 years).ResultsPET/CT sensitivity was superior to CIM's concerning lymph node involvement (100% versus 83%, respectively) and metastases detection (100% versus 50%, respectively). PET/CT results changed therapeutic management in 11% of cases. After three courses of chemotherapy, the rate of complete response was 66% with PET/CT versus 8% with CIM. Five percent of patients relapsed during follow-up (median = 5 years).ConclusionThis study confirms that PET/CT depicts important additional information in initial staging of paediatric rhabdomyosarcomas and suggests a superior prognostic value of PET/CT in early response to chemotherapy assessment.