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Resume Objectif Cet article se propose de montrer l’interet de la tractographie couplee a l’IRM fonctionnelle pour « tracer » in vivo des voies visuelles en combinant : (1) l’imagerie en tenseur de diffusion et la tractographie et (2) l’imagerie fonctionnelle (IRMf). Materiels et methodes Les voies visuelles ont ete reconstruites chez 205 sujets, sains et pathologiques. Onze cas ont beneficie, en plus, d’une acquisition en IRM fonctionnelle (effet BOLD), utilisant une stimulation par damiers noir-blancs clignotant. L’acquisition a ete pratiquee sur IRM 3.0 Tesla GEHC. Les donnees de neurotractographie et de l’IRMf ont ete secondairement fusionnees, ce qui constitue la neurotractographie fonctionnelle. Resultats et discussion Les principaux segments des voies visuelles ont ete reconstruits en tractographie : les nerfs optiques, le chiasma optique, les tractus et les radiations optiques, ainsi que la decussation de fibres dans le chiasma optique (de possibles voies directes hypothalamiques et thalamiques ont ete egalement identifiees). Conclusions L’imagerie en tenseur de diffusion constitue une methode prometteuse pour le diagnostic des maladies neurologiques. L’utilisation d’algorithmes informatiques sophistiques donne acces a l’anatomie in vivo. De plus, les cartes d’activation IRMf peuvent etre superposees sur les cartes d’anisotropie. La tractographie reliant deux regions d’un meme reseau fonctionnel renseigne ainsi sur la connectivite structurale sous-jacente. On parle en consequence de neurotractographie fonctionnelle.

Resume Introduction Les hematomes sous-retiniens spontanes ou associes a une degenerescence maculaire liee a l’âge (DMLA) sont habituellement de diagnostic clinique. Dans certains cas, l’aspect expansif pseudo-tumoral et la localisation peripherique de l’hematome peuvent faire evoquer une lesion tumorale. Le role de l’imagerie (echo Doppler, IRM) est alors important pour eliminer un melanome choroidien. Patients et methodes Les caracteres cliniques, echographiques et IRM des patients, adresses a l’institut Curie pour suspicion de melanome choroidien durant la periode 1998-2006, et dont le diagnostic final etait un hematome choroidien, ont ete revus. Les elements semiologiques du diagnostic differentiel avec les melanomes sont exposes. Resultats Quatre-vingt-quinze patients, âges de 54 a 92 ans (moyenne : 77 ans), ont ete suivis pour hematome choroidien. Vingt-sept patients avaient des antecedents de DMLA et 11 patients etaient traites par anticoagulant. Le fond d’œil mettait en evidence une hemorragie intravitreenne chez 18 patients et une localisation posterieure de la lesion chez 28 patients. L’epaisseur mesuree en echographie B standard etait de 1 a 7,8 mm (moyenne : 2,86 mm). Une IRM a ete pratiquee chez 27 patients et une echographie Doppler chez 11 patients. A l’echographie Doppler, les hematomes apparaissaient lineaires ou en dome regulier, hyperechogenes, sans vascularisation intralesionnelle en Doppler. A l’IRM, les hematomes apparaissaient en net hypersignal spontane en ponderation T1, de signal heterogene en T2 en rapport avec l’evolution du caillot, sans prise de contraste intralesionnelle. L’evolution en imagerie montrait une organisation progressive du caillot et une regression lente. Conclusion Le diagnostic des hematomes choroidiens est clinique. Dans certaines localisations posterieures pseudo-tumorales, l’echographie Doppler et l’IRM sont contributifs pour les differencier d’une tumeur.

We conducted study to determine whether and how the expression of the hypoxia-inducible factor 1alpha (HIF-1alpha) gene relates to outcome in patients with epithelial ovarian cancer. A total of 66 patients with epithelial ovarian cancer, who underwent primary surgery followed by platinum-based chemotherapy, were entered into this study. We confirmed the expression of HIF-1alpha and the vascular endothelial growth factor (VEGF) by immunohistochemistry. To determine the quantity of HIF-1alpha and VEGF expression, messenger RNA of each gene was measured by real-time reverse transcription-polymerase chain reaction. The cutoff values were determined by the receiver-operating characteristic curve according to survival. The protein expressions of HIF-1alpha and VEGF were strongly observed in the cancer cells. The cutoff value of HIF-1alpha and VEGF gene expression was 6.0 and 3.0, respectively. The expression of HIF-1alpha did not relate to clinical stage, but tumor with low VEGF expression was observed more frequently in stage I patients. The response rate to chemotherapy did not differ between high and low expression of both genes. The overall survival for patients with high expression of HIF-1alpha was significantly lower, but disease-free survival did not differ between high and low expression of HIF-1alpha, whereas both overall and disease-free survival for patients with high expression of VEGF were significantly lower. Multivariate analysis revealed that FIGO stage and HIF-1alpha expression were independent prognostic factors but that VEGF was not. The present study suggested that the expression level of HIF-1alpha could be an independent prognostic factor in epithelial ovarian cancer.

Objectif Le but de cette etude est d’evaluer la reponse corticale apres stimulation visuelle chez des sujets amblyopes unilateraux apres traitement. Materiel et methodes L’exploration clinique et en IRM fonctionnelle a ete effectuee chez des patients amblyopes unilateraux (7 hommes et 3 femmes, de 21 a 59 ans), traites dans leur enfance pour strabisme. Apres evaluation de l’acuite visuelle actuelle, dix patients furent examines en IRM fonctionnelle. Quatre sessions d’etude monoculaire furent realisees (deux sessions par œil) avec une presentation de damiers noirs-blancs clignotant a des frequences spatiales et temporelles de 1°/8 Hz et 15′/4 Hz. Un realignement anatomique des 4 sessions precedait une analyse statistique (logiciel SPM 99 Statistical Parametric Mapping ® ) mettant en evidence la reponse corticale apres stimulations de l’œil sain et de l’œil amblyope. Resultats et discussion Les reponses corticales visuelles tendent a distinguer deux groupes de patients amblyopes : dans un groupe d’acuite visuelle residuelle superieure ou egale a 7/10 e , la stimulation de l’œil atteint montrait un surcroit d’amplitude de la reponse corticale dans les aires visuelles principales, notamment V1, V3 et V5. Dans le 2 e groupe d’acuite inferieure a 7/10 e , la stimulation de l’œil amblyope induisait une reponse de moindre amplitude dans ces aires. Une activation supplementaire etait notee en regions orbito-frontales, prefrontales, parietales, dans les cuneus et les gyrus linguaux. Ces resultats suggeraient une reponse corticale visuelle differente en fonction de l’efficacite du traitement de l’amblyopie : une acuite visuelle subnormale correspondait a une receptivite corticale amelioree par rapport a la stimulation de l’œil sain, alors qu’une acuite deficiente correspondait a une faible reponse des aires visuelles principales, avec un recrutement d’activation d’aires secondaires dans un processus attentionnel contribuant a la reconstruction de l’image percue. Les effets de la plasticite corticale secondaire au traitement initial de l’amblyopie etaient retrouves meme des annees apres le traitement initial. Conclusion L’etude suggere l’importance d’un traitement efficace et precoce de l’amblyopie dans l’enfance, renforcant la receptivite du cortex visuel primaire et la participation d’aires visuelles secondaires dans un processus attentionnel pour l’analyse du message visuel provenant de l’œil anciennement amblyope.

Objectif Etude de la reponse corticale a la stimulation visuelle chez des sujets presentant une degenerescence maculaire liee a l’âge (DMLA). Materiel et methodes Nous avons realise une etude prospective en IRM fonctionnelle chez 10 patients presentant une DMLA uni- ou bilaterale, et 5 temoins d’âge comparable. Le paradigme de stimulation visuelle comporte une succession de phases de repos avec presentation d’un point de fixation centre sur fond d’ecran noir, suivie de phases d’activation avec presentation d’eclairs lumineux a 2 Hz de frequence temporelle. Les images IRM sont anatomiquement realignees ; les modifications du signal par effet BOLD, correspondant a la reponse vasculaire de l’activation neuronale, sont calculees en utilisant le logiciel SPM 99. Resultats Le premier objectif est d’evaluer la faisabilite d’une etude fonctionnelle chez les sujets âges. Temoins et patients se sont plaints de la duree de l’examen, bien que chacune des 2 phases fonctionnelles actives dure seulement 4 minutes 30. La fixation du point central est alteree pour les patients. Des mouvements trop importants ont entraine l’elimination de deux patients et d’un temoin du traitement statistique final. Discussion Cette etude est l’une des rares explorations IRM fonctionnelle du sujet âge, du fait des conditions techniques de realisation, de la fragilite du sujet et de sa pathologie ophtalmologique. Cependant, avec une information renouvelee et une optimisation de la stimulation visuelle, nous avons pu valider les reponses vasculaires d’activation neuronale pour la majorite des sujets. L’imagerie fonctionnelle des voies visuelles retrochiasmatiques apparait applicable en pratique clinique meme chez les sujets d’âges avances.

Objectif, materiel et methodes Evaluation en IRM fonctionnelle de la reponse corticale, apres stimulation visuelle chez des sujets atteints de DMLA neovasculaire apres photocoagulation. Les atteintes sont unilaterales chez 5 patients et bilaterales chez 5 patients. Cinq temoins sont egalement explores selon les memes modalites. Resultats Sur les 10 patients, 8 montrent des reponses corticales significatives, ainsi que 4 des 5 temoins. Nous avons effectue une comparaison individuelle des stimulations des cotes sain et atteint, du fait du nombre restreint de patients et de l’heterogeneite du tableau clinique des groupes examines. Chez les temoins, une stimulation du cortex visuel primaire, notamment en projection maculaire et perimaculaire bi-hemispherique, a ete observee. Les patients presentaient une restriction quantitative de la reponse corticale, une exclusion du cortex visuel primaire a projection maculaire apres stimulation de l’œil atteint, une activation etendue des aires visuelles peristriees et secondaires et une asymetrie hemispherique de reponse corticale pour certains sujets. Discussion Cette etude montre une relative correspondance entre l’importance de l’atteinte clinique et l’activation corticale pour chaque sujet. Cependant, elle a revele certaines particularites. i) A acuite visuelle comparable, la reponse corticale varie d’un patient a l’autre ; outre la compliance subjective du patient, la persistance de zones retiniennes maculaires intra-lesionnelles encore fonctionnelles pourrait influer sur la fonction visuelle objective. ii) L’asymetrie hemispherique correspondrait a une modification du champ visuel due a la deviation du regard vers une neomacula lateralisee. iii) L’activation notable des aires secondaires suggere une modification des interactions neuronales visuelles, par levee du feed-back negatif par le cortex strie maculaire. iv) Les modeles d’activation corticale doivent tenir compte de parametres physiologiques specifiques induisant une variabilite de la reponse vasculaire du sujet âge. Conclusion Malgre la difficulte de l’exploration, nous avons abouti a des observations reproductibles de reponse cerebrale dans la DMLA revelant un appauvrissement de l’activation corticale primaire et un renforcement des aires peripheriques. Ces premiers resultats devront etre valides dans une plus grande population de sujets atteints de DMLA, qui fera l’objet au prealable d’une information adequate.

Les collections d'anatomie de l'universite Paris V presentent un ensemble de dissections et de cires anatomiques tres anciennes, de tres haute qualite et parfaitement conservees, ayant servi a l'enseignement de l'anatomie et classees au patrimoine des monuments historiques depuis 1992.

A seismic probabilistic risk assessment (PRA) method has been applied to evaluate the safety of nuclear reactor buildings during earthquakes. Improvement was made to two methods (based on linear response and based on non-linear response) of fragility analysis in seismic PRA. The conventional method, which is based on linear response, considers increases of seismic capacity implicitly, using the non-linear behaviour of the structure. We described how to evaluate the capacity increase factor for the linear response method. Secondly, we proposed a method based on the non-linear response and a stratified two-point estimation method which can efficiently evaluate the variability of non-linear responses. We applied the two method to a PWR-type nuclear reactor building and ascertained that these method are useful and effective.

The aim of this magnetic resonance imaging study was to find a geometrical characterization of the deeper part of the corpus callosum. Its shape was studied in 12 middle-aged persons free of white matter pathology. Profiles of curvatures were measured showing that this surface was close to a minimal one, especially at the genu and near the splenium. To assess the effect of a white matter pathology on these geometrical features, the same measurements were performed in an extra group of nine patients with definite multiple sclerosis. The hypothesis of curvatures profiles parallelism for the two groups could be rejected at the 0.05 confidence level for the mean curvatures but not for the Gaussian ones. Curvatures profiles may give indications on balance between the cortex and the fiber bundles growth rates during the development and on large scale modifications cooccurring with multilocular white matter pathologies.

This study retrospectively investigated the significance of whole body CT (WCT) for patients with sepsis. A medical chart review was retrospectively performed for all patients with systemic inflammatory response syndrome that were treated initially between April 2011 and March 2012. The subjects were divided into a WCT group that underwent WCT on arrival and a control group. Results of this study suggested that WCT for sepsis was useful for elderly patients whose chief complaint or physiological findings could not suggest the anatomical site of infection, to determine the infectious focus and indications/method for surgery, to diagnose the basic diseases associated with opportunistic infections and to evaluate complicated diseases, {"references":["","R.P.Dellinger , M.M.Levy, J.M.Carlet, et al, \"Surviving Sepsis\nCampaign: International guidelines for management of severe sepsis and\nseptic shock,\" Crit Care Med vol.36, pp296-327, 2008.","C.P. Bleekr-Rovers, F.J.Vos, E.M.Kleijn, et al, \"A prospective\nmulticenter study on fever of unknown origin: the yield of a structured\ndiagnostic protocol,\" Medicine (Baltimore), vol.86,pp26-38, 2007.","J.Barkhausen, F.Stöblen, E.Dominguez-Fernandez, et al, \"Impact of CT\nin patients with sepsis of unknown origin,\" Acta Radiol vol.40, pp552-5,\n1999.","G. Kumar, N. Kumar, A Taneja, et al, \"from the Milwaukee Initiative in\nCritical Care Outcomes Research (MICCOR) Group of Investigators.\nNationwide trends of severe sepsis in the 21st century (2000-2007),\"\nChest vol.140, pp1223-31, 2011.","S.Huber-Wagner, R.Lefering, L.M.Qvick, et al; Working Group on\nPolytrauma of the German Trauma Society, \"Effect of whole-body CT\nduring trauma resuscitation on survival: a retrospective, multicentre\nstudy,\" Lancet, vol 373, pp1455-61,2009.","T.Nagai, C.Inoue, K.Tonouchi, et al,\"Multiple Organ Failure Followed by\nIntrauterine Klebsiella Pneumoiiiae Infection Associated with Diabetes\nMellitus,\" Kitakanto Med J vol.59, pp151-5, 2009. In Japanese","Y.Eriguchi, S.Ri, N.Fujimura,et al, \"A case of invasive Group A\nStreptococca1 infection,\" Rinsho to Kenkyu vol.89, pp111-3, 2012. In\nJapanese","T.Fujiwara, T.Nagai, K.Kaneko, et al, \"Candida Glabrata Fungemia After\nAmputation of an Infected Diabetic Foot,\" Kitakanto Med J vol.60,\npp259-63, 2010. In Japanese","Y.Yanagawa, Y.Hirano, N.Matsumoto, et al, \"Emphysematous\npyelonephritis induced by Citrobacter freundii,\" J Emerg Trauma Shock\nin press.\n[10] M.Gotthardt, C.P.Bleeker-Rovers, O.C.Boerman, et al, \"Imaging of\ninflammation by PET, conventional scintigraphy, and other imaging\ntechniques,\" J Nucl Med vol.51, pp1937-49, 2010.\n[11] S.M.Opal, T.D.Girard, E.W.Ely, , \"The immunopathogenesis of sepsis in\nelderly patients,\" Clin Infect Dis. Vol.41 Suppl 7, ppS504-12, 2005.\n[12] D.J.Brenner, E.J.Hall, \"Computed tomography: An increasing source of\nradiation exposure,\" N Engl J Med vol. 357, pp2277-84, 2007."]}

The frontal eye field and parietal eye field are known to be involved during visually guided saccades. As the location of the human parietal eye field is not yet well known, functional MRI was used during such a saccade task to better localise this field. Besides activity in visual areas of the occipital cortex, bilateral activity was seen in the precentral sulcus, corresponding to the frontal eye field, and in the deep region of the intraparietal sulcus. It is suggested that this intraparietal area, bordering areas 39 and 40 of Brodmann, corresponds to the human parietal eye field.

Summary Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited arterial disease of the brain recently mapped to chromosome 19. We studied 148 subjects belonging to seven families by magnetic resonance imaging and genetic linkage analysis. 45 family members (23 males and 22 females) were clinically affected. Frequent signs were recurrent subcortical ischaemic events (84%), progressive or stepwise subcortical dementia with pseudobulbar palsy (31%), migraine with aura (22%), and mood disorders with severe depressive episodes (20%). All symptomatic subjects had prominent signal abnormalities on MRI with hyperintense lesions on T2-weighted images in the subcortical white-matter and basal ganglia which were also present in 19 asymptomatic subjects. The age at onset of symptoms was mean 45 (SD [10·6]) years, with attacks of migraine with aura occurring earlier in life (38·1 [8·03] years) than ischaemic events (49·3 [10·7] years). The mean age at death was 64·5 (10·6) years. On the basis of MRI data, the penetrance of the disease appears complete between 30 and 40 years of age. Genetic analysis showed strong linkage to the CADASIL locus for all seven families, suggesting genetic homogeneity. CADASIL is a hereditary cause of stroke, migraine with aura, mood disorders and dementia. The diagnosis should be considered not only in patients with recurrent small subcortical infarcts leading to dementia, but also in patients with transient ischaemic attacks, migraine with aura or severe mood disturbances, whenever MRI reveals prominent signal abnormalities in the subcortical white-matter and basal ganglia. Clinical and MRI investigations of family members are then crucial for the diagnosis which can be confirmed by genetic linkage analysis. The disease is probably largely undiagnosed.

This article shows that functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) are very useful in the in vivo description of the visual pathways using today's most advanced techniques and allowing fusion between fMRI and tractography. Two complementary techniques were combined: (1) DTI coupled with the tractography and (2) fMRI.A group of 205 cases, normal and pathological, children and adults, were studied for tractographic reconstitution of visual pathways. In addition, 11 patients underwent an acquisition in fMRI (BOLD effect), with a stimulation of a black-and-white flickering checkerboard. Acquisition was carried out on a 3.0 Tesla GEHC MRI unit. Activated arrays of fMRI are overlaid with those of neurotractography (neural tractography) having like results a functional neurotractography.The main components of the visual pathways were successfully reconstructed in tractography: the optic nerves, optic chiasm, optic tracts, and optic radiations. It was also possible to visualize fiber decussation within the chiasma (possible direct pathways to the hypothalamus and thalamus were also identified).The tensor of diffusion is increasingly used and is a promising technology to improve the diagnosis of neurological diseases. Sophisticated algorithms contribute a new vision of the anatomy, with the possibility of isolating distinct anatomical entities. With the software used, the charts of fMRI activation are overlaid on the anisotropy charts. The tractograms that link two regions of the same functional network thus provide information on subjacent structural connectivity. Consequently, one speaks about functional neurotractography.

After 13 years of glaucoma exploration using MRI at 1.5 and 3 Tesla, we have deduced that there is no specific characteristic between the different forms of this disease, which is manifested by a slowly progressing degenerative optical neuropathy, predominant from front to back (with volume of the optic nerve head always greater than the distal portions of the 2nd neurone, chiasma, and optic tract), interspersed with clinical flare-ups that are recognized by an intense localized hypersignal (frequently from the apex progressing along the canal). Visual tract involvement is always bilateral, even in cases where symptoms are exclusively unilateral (asymmetry can be observed in these cases). The discordance between (i) the severity of axon reduction and (ii) the signs of injury already present at the time when MRI is performed and the relative preservation of visual function argues for encephalic disease with visual involvement. Its delayed discovery makes treatment, even with neuroprotectors, less effective and points toward the need for implementing directed genetic prevention studies, as a first step to more effectively assessing the therapies available.

Detail the most frequent problems encountered in the differential diagnosis of retinoblastoma.and method: We conducted a retrospective study on the children referred to the Curie Institute for suspicion of retinoblastoma between 2000 and 2006. Diagnosis was made by fundus examination using the indirect ophthalmoscope, ultrasonography, and MRI.Of the 486 children seen during this period, 408 had unilateral or bilateral retinoblastoma and 78 (16%) had another lesion: Coats disease (20 children, 25%), congenital malformations (23 children, 30%; coloboma, PHPV, microphthalmia, isolated or associated with retinal dysplasia), other tumors (10 children, 13%; astrocytomas and medulloepithelioma), combined hamartomas (six children, 8%), inflammatory diseases (six children, 8%) (Toxocara canis, cat scratch eye disease, or toxoplasmosis), and other diseases (13 children, 16%; corneal opacities, congenital cataract, or retinal detachment).Compared to previous series, this study shows the proportion of erroneous diagnosis has lowered (16%) compared to earlier studies by Balmer (1986; 30%), and Shields (1991; 42%). No cases of retinopathy of prematurity were seen in our series, demonstrating that screening is good or of a lower frequency in France. The frequency of PHPV has dropped. Coats disease remains a frequent and sometimes difficult diagnosis to make, particularly in advanced stages of the disease.

International audience; Fried syndrome, first described in 1972, is a rare X-linked mental retardation that has been mapped by linkage to Xp22. Clinical characteristics include mental retardation, mild facial dysmorphism, calcifications of basal ganglia and hydrocephalus. A large four-generation family in which the affected males have striking clinical features of Fried syndrome were investigated for linkage to X-chromosome markers; the results showed that the gene for this condition lies within the interval DXS7109-DXS7593 in Xp22.2. In total, 60 candidate genes located in this region, including AP1S2, which was recently shown to be involved in mental retardation, were screened for mutations. A mutation in the third intron of AP1S2 was found in all affected male subjects in this large French family. The mutation resulted in skipping of exon 3, predicting a protein with three novel amino-acids and with termination at codon 64. In addition, the first known large Scottish family affected by Fried syndrome was reinvestigated, and a new nonsense mutation, p.Gln66X, was found in exon 3. Using CT, both affected patients from the French family who were analysed had marked calcifications of the basal ganglia, as previously observed in the first Scottish family, suggesting that the presence of distinctive basal ganglia calcification is an essential parameter to recognise this syndromic disorder. It may be possible to use this feature to identify families with X-linked mental retardation that should be screened for mutations in AP1S2.

Functional MRI evaluation of the cortical response in treated amblyopic patients.Clinical and functional MRI exploration of ten patients, seven men and three women aged from 21 to 59 years, with strabismus management during childhood. Functional evaluations were performed on a 1.5 Tesla MR device, with four monocular functional sessions, two stimulations per eye. Alternating rest and active phases displayed still and flickering black and white checkerboards with spatial and temporal frequencies of 1 degree/8Hz and 15'/4Hz. Anatomical realignment and statistical analysis were performed using SPM99 (Statistical Parametric Mapping) to compare the four sessions in individuals.In patients presenting a visual acuity of the amblyopic eye less than 0.7, stimulation of this eye induced lower response in V1, V3, and V5 in comparison with the contralateral eye stimulation. Unexpectedly, in patients recovering normal or subnormal acuity, the amblyopic eye gave comparable or enhanced response in these areas. Additional response was found in the secondary visual cortex, the cuneus, the lingual gyrus, and in parietal, frontal, and orbitofrontal areas. These results suggest a variation in cortical response depending on the efficacy of the treatment. Recovered amblyopic eye, even with acuity less than the contralateral eye, may induce a reinforced cortical sensitivity to visual stimulus. Secondary visual areas may contribute to an attentional process in image perception and analysis. Cortical plasticity may be observed several years after amblyopia treatment.Our study substantiates the importance of an effective and early treatment of functional amblyopia, inducing cortical plasticity with reinforced attention and sensitivity to visual perception.

Arteriovenous malformations of the brain (BAVMs) are a relatively rare group involving intracranial vascular lesions (telangiectasia, cavernous malformation, venous anomaly). We report the case of a patient who presented an atypical visual symptomatology revealing a BAVM.A 48-year-old woman consulted for a recent bilateral visual blur. In darkness, discrete anisocoria appeared on the left eye. At the biomicroscopy light examination, we found areflexic semi-mydriasis (direct and consensual) on the left eye; the light reflex (direct and consensual) on the right eye was normal. During the accommodative reflex test the left pupil contracted. We propose the diagnosis of Adie's pupil, which was confirmed by the pilocarpine test (0.125%). We decided to examine the visual field because the symptomatology of the visual blur remained unexplained. The visual field showed a left homonymous inferior lateral scotoma. MRI showed a right occipital arteriovenous malformation.A quick examination could confuse painless anisocoria with a compression of the IIIrd intrinsic left nerve. This recent scotoma revealed BAVM progression. The natural history of BAVMs shows that the essential risk of these injuries is the onset of an intracranial hemorrhage. To reach a radical therapeutic decision, a cerebral arteriography clarifying the afferent and efferent vascularity of the nidus was carried out.This case is original in that it associates the concomitant discovery of a BAVM and Adie's pupil. Symptomatic BAVMs are extremely serious. Planning their treatment requires multidisciplinary cooperation in order to reduce the risk of mortality.

Water diffusion analysis in magnetic resonance imaging (MRI) provides an elective visualization of fiber tract orientations in cerebral white matter, especially for optic tracts. We explored 25 patients from 18 to 45 years of age, with normal MRI in 20 subjects, and radiological anomalies in five. On a 1.5 Tesla MRI apparatus, diffusion tensor acquisitions were performed in 5 minutes 58 seconds with an EPI Single Shot sequence covering the entire brain. Image displacements were precluded by patient information and adequate fixation, then digitally corrected on workstations. Volume merging and fiber tract extraction were achieved using dedicated software (Volume-One and dTV). A directional depiction was obtained for all areas in the white matter, in particular for white matter junctions. Coming from the lateral geniculate body, the optic tracts were directed posteriorly toward the occipital cortex, with numerous connections to extrastriate associative areas, and through the corpus callosum and the fornix. Diffusion tractography requires optimization of volume displacements, before and secondary to MRI acquisitions. Our diffusion tensor acquisition, with image optimization in a short-duration sequence can be routinely applied to all patients, for a specific analysis of functional connections between cortical areas of cerebral white matter.

This paper evaluates factors influencing the total cost of reinforced concrete (RC) members during their service life when structures gradually deteriorate and require maintenance work. The form of deterioration considered herein is salt attack, and the repairing method involves restoration of the member to its original cross-section. Total maintenance cost is expressed as present cost based on the coefficient of current price. The main factors calculated are the deterioration ratio of RC members at the repair stage, the actual interest ratio, and the cost loss for expected structural failure. Calculation results indicate that the life cycle cost of a structure is greatly affected by these factors, and that they have to be decided carefully.

The Museum of anatomy of the University Paris V exhibits a collection of ancient and high quality dissections and waxworks, very well preserved, which were used for teaching anatomy and have been classified historic monument since 1992.

Nedaplatin (cis-diammine-glycolato platinum: CDGP) is a platinum compound with a molecular weight of 303.18 that was recently developed in Japan. There have been reports of the antineoplastic effects of Nedaplatin on cancers in the cranio-cervical region, lung, esophagus, urinary bladder, testis, ovary, and uterus. In this study, we performed combined therapy of CDGP and fluorouracil (5-FU) for 8 patients with oral cancers, and evaluated the results to elucidate the clinical effect and adverse side effects. The subjects were 8 patients with squamous cell carcinoma (5 males and 3 females aged 33-65 years). The primary carcinoma regions were the tongue in 5 patients, oral floor in 2 patients, and mandibular gingiva in 1 patient. The T-classification was T2 in 6 patients and T4 in 2 patients, and the clinical staging was Stage II in 5 patients, Stage III in 1 patient and Stage IV in 2 patients. We first administered 700 mg/m2 5-FU per day from day 1 to day 5 (total dose 3,500 mg/m2), then 90 mg/m2 CDGP on day 5. The clinical effect was evaluated as a partial response in all cases, showing a 100% success rate. The histopathological findings of resected tumors were evaluated by Ohboshi and Shimozato's classification. One patient was Grade IIA, 5 patients Grade IIB, and 2 patients Grade III. The adverse side effects were slight myelotoxicity, gagging, nausea, alopecia, and stomatitis less than Grade II. Although the oral cancers in this study were extroverted superficial ulcerative cancers, and the number of patients was low at 8, this combined therapy is considered useful and worth evaluating in further accumulated cases.

5'-DFUR is a pro drug of 5-FU, which is known to be converted by thymidine phosphorylase (dThdPase). A recent pre-clinical study revealed that CPA upregulates dThdPase activity specifically in tumor cells. Furthermore, clinical trials have shown significant response rates in breast cancer patients, when using the chemotherapy combination of 5'-DFUR, CPA and MPA. The purpose of this study was to examine the efficacy of this regimen as a pain reduction therapy for breast cancer patients with bone metastasis. Ten patients who had bone metastasis with restricted ADL were included in the study. All of the patients had had previous exposure to such standard chemotherapy as CAF, CMF, taxol and oral 5-FU administration. The patients were administered daily oral doses of 5'-DFUR at 800-1,200 mg, CPA at 200 mg and MPA at 400-800 mg for two weeks as induction therapy, followed by two weeks rest (one to two cycles). Daily dose of 800 mg of 5'-DFUR, 100 mg of CPA, 400-800 mg of MPA was continuously administered thereafter. The main findings included a significant decrease in pain in eight patients, which continued for more than 6 months. In five patients, the effect lasted more than one year. As the pain decreased, the patients' QOL was improved. Hematological toxicity of more than grade 3 was observed in three patients but only during the induction therapy. One patient had pulmonary thrombosis and required hospitalization. In conclusion, oral administration of 5'-DFUR/CPA/MPA is well tolerated and useful in reducing pain.

We reported a retrospective study of 27 children (mean age = 10 years), who presented a loss of vision due to an acute optic neuritis, between 1982 and 1997. The symptoms ar more likely bilateral in children, and frequently associated with systemic viral infection or hepatitis B vaccination. Multiple sclerosis occurs approximately in 20 p. cent of the cases, i.e. less frequently than by adults. Magnetic resonance imaging is now systematic: in 20 children hyperintense nodular abnormalities in a various distribution was demonstrated by 9 children. During the follow-up, 23 eyes of 27 have an excellent recovery of vision, but 4 patients have developed multiple sclerosis. Corticotherapy was uses in 23 cases, in the form of methylprednisolone intravenous flashes in 14 cases.

Analyzing a personal series of children with acute optic neuritis (AON), we studiedA retrospective study of 28 eyes in 20 patients (mean age: 10;7 years), examined between 1982 and 1997, with a follow-up ranging from 6 months to 15 years (mean: 5;5 years). We recorded etiologic factors, clinical features (ocular and extra ocular), biological results, and neuroimaging findings.Initial involvement was uni- or bilateral with poor visual acuity (under 20/200 in 22 eyes of 28). Intracerebral inflammation was present in 9 of 13 cases where MRI was performed. We found a cause in only 7 cases (5 viral diseases and 2 recent vaccinations against hepatitis B). Visual recovery was good (over 20/25 in 20 eyes of 28) whatever the treatment, but AON recurred in 5 children. Four children later developed multiple sclerosis.The cause of AON is rarely found. After eliminating an infection, we retained viral disease, complication of a recent vaccination against hepatitis B, and neurological diseases. MRI was the imaging study of choice. Development of multiple sclerosis occurred in 4 cases of 20, the same frequency as in the literature. The risk of later development of multiple sclerosis was 20%. Progression of AON was often excellent. Nevertheless, corticotherapy was added, in form of intravenous boluses followed by decreasing oral therapy for one month.

We investigated neurochemical abnormalities in the normal-appearing white matter (NAWM) on MRI of patients with optic neuritis (ON) and compared them to those of patients with multiple sclerosis (MS). Patients with ON (42) were classified into three groups according to abnormalities on brain MRI. Patients with MS (55) were devided in two groups: relapsing remitting MS (RRMS) and secondary progressive MS (SPMS). All patients underwent MRI of the brain and localised proton magnetic resonance spectroscopy (MRS) of NAWM. The results were compared to those of 15 controls. Patients with MS had significant abnormalities compared with controls and with patients with ON. Patients with RRMS and those with ON had comparable MRS parameters, while patients with SPMS had significant spectroscopic abnormalities in comparison with controls, but also with patients with RRMS. These changes consisted of a decrease in N -acetylaspartate, a neuronal marker, which may reflect axonal dysfunction and/or loss. MRS abnormalities were detected in 14 patients with ON (27 %). The main abnormalities consisted of a decrease in N -acetylaspartate, an increase in choline-containing compounds at long echo times, and the presence of free lipid peaks at short echo times. MRS of the NAWM on MRI may prove useful for detecting neurochemical brain abnormalities in ON not visible on MRI.

We present a case of a large mucocele pressing the orbit forward and compared our findings with those reported by others.A 23-year-old woman was examined for an inflammatory tumor of the internal canthus. She had a 6/10 vision loss of the left eye, diplopia, and non-axial exophthalmos. CT scan and magnetic resonance imaging evidenced a huge sinus mucocele behind the orbit. Surgery using the paralateronasal approach was performed. Pathology confirmed the diagnosis of mucocele.Ophthalmic complications of mucoceles result from tumor growth leading to compressive optic neuropathy or even compression of the chiasma. A sinus mucocele should be suspected upon indirect clinical signs and lead to neuroradiological explorations. Magnetic resonance imaging reveals iso- or high signals on T1-weighted sequences and high signal on T2-weighted sequences. MRI evidences intracranial or orbital extension. CT scan reveal the degree of bone erosion. Prognosis is favorable after surgical treatment. It is important to correctly diagnose mucocele on the basis of clinical and neuroradiological findings in order to propose early surgery and prevent permanent visual loss by compressive optic neuropathy.

In case of 5-fluorouracil (5-FU)/leucovorin (LV) treatment, which is one of the most effective forms of chemotherapy for colorectal carcinoma, 5-FU is usually continuously infused from the venous route. However, since this continuous infusion limits the patients' active daily life, oral administration is preferable. In the present study, we evaluated the efficacy and side effects of orally administered 5-FU/LV.In the continuous intravenous infusion group (civ group), colon 26 bearing mice were cannulated into central vein from external jugular vein. From this route, either 5, 10, or 20 mg/kg of 5-FU was continuously infused for 7 days (n = 6). In another group, either 10, 20, 40 mg/kg of 5-FU was infused orally (po group, n = 6). The other 6 animals were used for the non-treatment group. In the next series, 100 mg/kg of LV was added for each group above. Tumor volume, thymidylate synthase inhibition rate (TSIR) and body weight were measured at the end of infusion. During the experimental period, mice had free access to chow and water.The tumor/control (T/C) volumes ratio showed that approximately twice the orally administered 5-FU dose had an anti-tumor effect equal to that of 5-FU administered intravenously. Synergic antitumor effects by LV were only revealed in the civ group. Significant body weight loss was recognized only in the po group at a 5-FU dose of more than 20 mg/kg. In summary, since the modulation effect of LV was recognized only with continuously intravenous infusion of 5-FU, further improvement of oral administration is required in the LV/5-FU combination therapy.

Persistent hyperplastic primary vitreous (PHPV) is a rare developmental malformation of the eye. This anomaly is usually unilateral and unassociated with other disease. PHPV may have clinical variations: an anterior and/or a posterior one. Diagnosis and treatment are exposed in our paper.We study 38 eyes in 34 patients. All patients had an anterior form of PHPV. Nine of them associated a posterior form. Eighteen eyes underwent surgery, the mean postoperative follow-up is 4.7 years. Treatment is discussed, depending on the initial form of PHPV. We report the evolution of the surgical eyes and the untreated eyes.Slit lamp examination and echographic findings (A-scan and B-scan) support the diagnosis. In some cases computed tomography or RMN can be useful. If the cataract is mild in the anterior form of PHPV, treatment of amblyopia and frequent clinical examination can be sufficient. If the cataract is dense, a lensectomy must to be performed. The surgical technique can be difficult. For the eyes with posterior PHPV, the surgical treatment is to be avoided, because of high risk of retinal detachment.PHPV may have clinical variations, mostly with cataract as major sign. In purely anterior presentation, in absence of marked microphthalmos, lensectomy can be useful.

Sneddon syndrome is characterized by the association of livedo reticularis and cerebrovascular ischemic events. Clinical and MRI aspects are described in 26 patients with Sneddon syndrome. MRI features were classified in 6 groups according to the aspect and topography of the lesions. No correlation was found between the presence of vascular risk factors, valvulopathy or antiphospholipid antibodies and the presence of dementia or MRI lesions. There was a significant correlation between MRI extension of the lesions and clinical disability. Clinical course and MRI findings are presented according to the treatment.

Currently, biochemical modulation for 5-fluorouracil (5-FU) is one of the most successful chemotherapy for both colo-rectal and gastric cancer. The purpose of this study is to evaluate the significance of measuring intratumoral thymidylate synthetase (TS) and folate (FH4) levels as predictive parameters for the successful treatment. Samples were collected from 16 advanced colo-rectal and 21 advanced gastric cancer. TS and tetrahydrofolate levels in the specimens were measured by binding assay. Results showed that there were no significant difference in TS levels between the different pathologic types of carcinoma. On the other hand, well (3.94 +/- 1.75 p mol/g) and moderately (5.95 +/- 2.69 p mol/g) differentiated carcinoma showed lower FH4 levels compared to poorly differentiated carcinoma (9.58 +/- 5.27 p mol/g). In conclusion, biochemical modulation by cisplatin or leucovorin, which elevates intratumoral folate levels, is more needed for well and moderately differentiated carcinoma. Finally, measuring TS levels can also be important because two cases who responded to cisplatin/5-FU chemotherapy showed low TS levels compared to the others who had lower response.

Cortical activity during eye movement was examined with functional magnetic resonance imaging. Horizontal saccadic eye movements and smooth pursuit eye movements were elicited in normal subjects. Activity in the frontal eye field was found during both saccadic and smooth pursuit eye movements at the posterior margin of the middle frontal gyrus and in parts of the precentral sulcus and precentral gyrus bordering the middle frontal gyrus (Brodmann's areas 8, 6, and 9). In addition, activity in the parietal eye field was found in the deep, upper margin of the angular gyrus and of the supramarginal gyrus (Brodmann's areas 39 and 40) during saccadic eye movement. Activity of V5 was found at the intersection of the ascending limb of the inferior temporal sulcus and the lateral occipital sulcus during smooth pursuit eye movement. Our results suggest that functional magnetic resonance imaging is useful for detecting cortical activity during eye movement.

Objectives—To characterise clinically a large French family aVected with cerebral cavernomas and to check for linkage of this condition to chromosome 7. Methods—A family,originating from Normandy and in which five members had undergone surgery for cavernomas, was extended. All members older than 18 were studied clinically and by neuroimaging. Genetic linkage analysis was conducted using 11 polymorphic microsatellite markers located between D7S502 and D7S479. Results—The family included three generations. Among the 25 members investigated, 11 had an abnormal cerebral MRI, eight of them being symptomatic, and 12 were asymptomatic with a normal MRI. The status of the two remaining members could not be established on the basis of clinical and MRI data. The family reported shares some striking features with other previously linked families—namely, a high clinical penetrance and the presence of multiple lesions within most of the aVected members. A lod score of 4.04 was obtained with marker D7S657 with no recombinant. Significant lod scores were also obtained with D7S524 (Zmax=3.32 at =0.00) and D7S630 (Zmax=3.44 at =0.00). These results establish linkage of the condition found in this family to chromosome 7. Haplotype analysis strongly suggests that the gene is telomeric to D7S802 and centromeric to D7S479. Conclusions—These data confirm linkage of cerebral cavernous malformations to chromosome 7 in a non-Hispanic family. (J Neurol Neurosurg Psychiatry 1997;63:40‐45)

The aim of this magnetic resonance imaging study was to find a geometrical characterization of the deeper part of the corpus callosum. Its shape was studied in 12 middle-aged persons free of white matter pathology. Profiles of curvatures were measured showing that this surface was close to a minimal one, especially at the genu and near the splenium. To assess the effect of a white matter pathology on these geometrical features, the same measurements were performed in an extra group of nine patients with definite multiple sclerosis. The hypothesis of curvatures profiles parallelism for the two groups could be rejected at the 0.05 confidence level for the mean curvatures but not for the Gaussian ones. Curvatures profiles may give indications on balance between the cortex and the fiber bundles growth rates during the development and on large scale modifications co-occurring with multilocular white matter pathologies.

Fifty six patients among whom 39 had white matter diseases had MRI of the brain comparing FLAIR sequence to a conventional proton density sequence. Flair sequence allowed to detect 18 additional hypersignal (HS) that were not present on T2 sequence. These HS were located in the periventricular areas for 5 of them, near the cortical sulci in 10, and in the centrum semi-ovale for 3. FLAIR sequence permitted analyze 41 other lesions that were not obvious on proton density sequences. Thirty five of them were thus confirmed to be HS : 31 in the paracortical areas, 3 in the paraventricular regions and one in the internal capsule, whereas the remaining 6 were normal sulci of the brain. FLAIR sequence increases the sensitivity of MRI in white matter diseases.

We used a rapid long TE proton magnetic resonance spectroscopic (MRS) sequence in the normal appearing white matter of 11 patients with definite multiple sclerosis (MS) localizing the volume of interest in the centrum semi-ovale. The metabolic changes were compared to the same area in 11 normal brains. We found a significant decrease in NAA/Cr ratios and a borderline significance of increase in Cho/Cr ratios in patients with MS. A discriminant analysis was performed on these data. This allowed to obtain a simple ratio, NAA/(Cho+Myo), which discriminated MS patients from controls. Our results indicate that normal appearing white matter on MRI is biochemically abnormal in patients with MS. In addition MRS could be routinely used after a standard MRI examination in patients with MS for clinical correlations, total load of the disease assessment and monitoring clinical trials.

Currently, biochemical modulation for 5-fluorouracil (5-FU) by cisplatin (CDDP) is one of the most successful forms of chemotherapy for gastric cancer. Although the mechanism of this modulation is thought to increase intracellular folate levels, it is still unknown how much CDDP is needed to elevate folate levels. The purpose of this study is to determine the appropriate volume of CDDP as a modulator for 5-FU. Either 5, 20, 100 mg/body of CDDP was administered intravenously to advanced gastric cancer patients just before operation. Four hrs later, the stomach was resected and folate levels were measured in the tumor and normal mucosa by thymidylate synthase binding assay. The results showed folate elevation only after administration of 100 mg/body of CDDP, both in the tumor and mucosa (p0.01). In conclusion, if CDDP is infused as a bolus, a relatively large amount is needed to modulate the intratumor folate level.

Objectives: To characterize the clinical, biological, and neuroradiological findings in Sneddon syndrome; to correlate magnetic resonance imaging abnormalities with disability, presence of hypertension and other vascular risk factors, presence of heart valvulopathy on echography, and titer of antiphospholipid antibodies; and to compare these findings in antiphospholipid-positive and antiphospholipid-negative patients. Design: Retrospective review of the records of 32 consecutive patients with livedo reticularis and neurological events, followed up in our institution between January 1991 and August 1995. Patients: Twenty-six patients (20 women and 6 men) who had at least 1 cerebral ischemic arterial event associated with generalized and pathological livedo reticularis. Results: The age at the first cerebral ischemic event ranged from 22 to 58 years. Motor deficit was the most frequent sign (found in 73% of cases). Disability was found in 50%, systemic hypertension in 65%, heart valvulopathy in 61%, and antiphospholipid antibodies in 42% of cases. Patients were classified in 6 groups according to magnetic resonance imaging findings. No correlation was found between the presence of hypertension or other vascular risk factors, valvulopathy, antiphospholipids, and magnetic resonance imaging abnormalities. There was no significant difference between antiphospholipid-positive and antiphospholipid-negative patients except for the presence of antinuclear antibodies. There was a significant correlation between the extent of magnetic resonance imaging abnormalities and disability. Conclusion: The severity of the disease seems to be correlated with magnetic resonance imaging aspects, but not to the presence of antiphospholipid antibodies. Magnetic resonance imaging may help to understand the natural course of the cerebral involvement of the disease.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited arterial disease of the brain recently mapped to chromosome 19. We studied 148 subjects belonging to seven families by magnetic resonance imaging and genetic linkage analysis. 45 family members (23 males and 22 females) were clinically affected. Frequent signs were recurrent subcortical ischaemic events (84%), progressive or stepwise subcortical dementia with pseudobulbar palsy (31%), migraine with aura (22%), and mood disorders with severe depressive episodes (20%). All symptomatic subjects had prominent signal abnormalities on MRI with hyperintense lesions on T2-weighted images in the subcortical white-matter and basal ganglia which were also present in 19 asymptomatic subjects. The age at onset of symptoms was mean 45 (SD [10-6]) years, with attacks of migraine with aura occurring earlier in life (38.1 [8.03] years) than ischaemic events (49.3 [10.7] years). The mean age at death was 64.5 (10.6) years. On the basis of MRI data, the penetrance of the disease appears complete between 30 and 40 years of age. Genetic analysis showed strong linkage to the CADASIL locus for all seven families, suggesting genetic homogeneity. CADASIL is a hereditary cause of stroke, migraine with aura, mood disorders and dementia. The diagnosis should be considered not only in patients with recurrent small subcortical infarcts leading to dementia, but also in patients with transient ischaemic attacks, migraine with aura or severe mood disturbances, whenever MRI reveals prominent signal abnormalities in the subcortical white-matter and basal ganglia. Clinical and MRI investigations of family members are then crucial for the diagnosis which can be confirmed by genetic linkage analysis. The disease is probably largely undiagnosed.

Article abstract—Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an autosomal dominant cerebral arteriopathy mapped to chromosome 19 and characterized mainly by recurrent subcortical ischemic strokes and extensive white-matter signal abnormalities (WMAs) on magnetic resonance imaging. Other clinical features include migraine attacks and progressive subcortical dementia. Herein, we describe several members of the same family who suffered migraine attacks, mostly with aura, associated with WMAs, segregating with an autosomal dominant pattern of inheritance. One individual had a progressive subcortical dementia with similar WMAs. Although ischemic stroke, one of the hallmarks of CADASIL, was not present in this family, we hypothesized that the present disorder resulted from an alteration of the CADASIL gene. Genetic linkage analysis, using four chromosome 19 markers spanning the CADASIL locus, supports this hypothesis.

To determine whether the length and depth of the calcarine sulcus are associated and can be used for estimating the size of the primary visual area (area 17) and other regions in MR images of the human occipital lobe.The length and depth of the calcarine sulcus and the projection areas of the mesial surface of the occipital lobe and of the total hemisphere were measured in MR images of 23 healthy subjects.A higher variability of the size of the projection area of the mesial surface of the occipital lobe compared with that of the remaining part of the hemisphere is found. The projection area of the mesial cortical surface of the occipital lobe is correlated with the length of the calcarine sulcus, but both parameters are not correlated with the depth of the calcarine sulcus and, therefore, also not with the size of the part of area 17 buried in the sulcus.The size of area 17 cannot be estimated by the length of the calcarine sulcus in MR images. Depth and length of the calcarine sulcus grow independently in the human brain. Different degrees of folding may cause the variability of architectonic areas.

Fourteen patients with recurrent breast cancer were treated with a combination of mitoxantrone (10 mg/m2 iv, day 1), vincristine (1 mg/m2 iv, day 1) and prednisolone (30 mg/day day 1-7). Cycles were repeated every 4 weeks and all patients received more than 3 cycles. The objective response rate was 70.0% (7 of 10). In two patients, the treatment has been continued now for more than one year. In these 2 patients, the duration of response is more than 40 weeks. The toxicity was primarily myelosuppression. Five of 14 patients (35.7%) had leukopenia of Grade 3 and 4. These patients received G-CSF therapy and recovered well from leukopenia. Nausea and vomiting were well tolerated, probably by prednisolone. This regimen was especially superior in the maintenance of quality of life because hair loss was much less compared to CAF (cyclophosphamide, ADM, 5-fluorouracil) treatment. In conclusion, MVP treatment is highly effective and safe for the treatment of recurrent breast cancer.

5-fluorouracil (5-FU)/methotrexate (MTX) sequential chemotherapy is one of the standard regimen for the treatment of gastric cancer. Though this combination therapy is highly effective, the mechanism is still unclear. In this study, we investigated the relationship between antitumor activity and the inhibition of thymidylate synthase and between antitumor activity and incorporation of 5-FU into RNA (F-RNA) in mice bearing Sarcoma-180 treated by tegafur alone (100 mg/kg) or by the combination of MTX (42 mg/kg) and tegafur (100 mg/kg). A new method for the determination of F-RNA of tumor tissue samples was used. Briefly, RNA fractions containing incorporated 5-FU were extracted by KOH hydrolysis. FUra in RNA fractions was released by HCl hydrolysis and its levels were determined by GC-MS. The results showed that the F-RNA levels were significantly elevated by the pretreatment of MTX. According to this result, it is suggested that the measurement of F-RNA levels together with the determination of FUra concentration and the inhibition rate of thymidylate synthase were considered as a good means for the evaluation of antitumor efficacy of FUra. We concluded that the impairment of RNA metabolism played a major role in the antitumor activity of MTX/5-FU combination.