[Medical reconciliation for hospitalized patients in orthopedic surgery department: Return of experience over 2 years of practice]. / Conciliation médicamenteuse à l'entrée des patients dans une unité de chirurgie orthopédique : retour d'expérience sur plus de 2 ans de pratique.

OBJECTIVES: Some medication errors can be prevented by pharmacist action such as medication reconciliation. The main objective of this study was to evaluate the medication reconciliation activity after two years of practice. The secondary objective was to assess the medical staff's satisfaction following the setting up of the activity. METHODS: This retrospective study was realized over a period of two years in our hospital. Patients meeting the following criteria were included: 65 years and over, hospitalized in orthopedic surgery department, preferentially after a discharge of the emergency room. After the best possible medication history was established, it is compared to medicines ordered. The discrepancies were defined as intended or unintended. Study data were collected and analyzed using Excel and SPSS statistics®. RESULTS: A total of 899 patients met the inclusion criteria during the study period, mean age was 78 years (27; 104). A total of 84 % of our cohort was admitted after a discharge of the emergency room. Seventy five percent of the population had at least an unintended discrepancie, a mean of 2,3 unintended discrepancies per patient was identified. Seventy five percent of the unintended discrepancy were discussed and resolved. The medical staff was mostly satisfied of the activity. CONCLUSION: The medication reconciliation secured the drug management of hospitalized patients.

Association of CTH variant with sinusoidal obstruction syndrome in children receiving intravenous busulfan and cyclophosphamide before hematopoietic stem cell transplantation.

Sinusoidal obstruction syndrome (SOS) is a severe complication of hematopoietic stem cell transplantation (HSCT) that can be fatal, often attributed to the conditioning regimen prior to HSCT. We evaluated the association of SOS risk with gene variants in cystathionase (CTH), an enzyme involved in glutathione synthesis, in 76 children receiving intravenous busulfan (Bu) before HSCT. Our results indicated an association with CTHc.1364 G>T (ORTT=10.6, 95% confidence interval (CI)=2.16, 51.54) and SOS risk, which was sex dependent (female patients, ORTT=21.82, 95% CI=3.590-132.649). The interaction between CTHc.1364 G>T and another risk variant (GSTA1*B) was explored. A recessive model with the use of GSTA1*B*B and CTH c.1364 TT genotypes proved to be useful at predicting SOS occurrence, indicating the possibility of using these gene variants as markers of SOS occurrence and to further individualize preemptive treatment aimed at reducing SOS incidence.

Role of operative airway evaluation in children with recurrent croup: a retrospective cohort study.

OBJECTIVE: Determine which risk factors in children with recurrent croup warrant bronchoscopic evaluation. DESIGN: Retrospective cohort study. SETTING: Tertiary paediatric hospital. PARTICIPANTS: Children with recurrent croup who underwent a rigid bronchoscopy between 2001 and 2013. MAIN OUTCOME MEASURES: Bronchoscopy findings, classified as normal, mildly abnormal or significantly abnormal. RESULTS: Two hundred and thirty-five children underwent a rigid bronchoscopy and 110 underwent a flexible oesophagoscopy. One hundred and forty-five children (61.7%) had a mildly abnormal exam, and 27 children (11.5%) had significant findings that required a surgical intervention or grade 2 or greater subglottic stenosis. The significantly abnormal group included 4 children with laryngomalacia, 2 with a subglottic cyst, 8 with grade 2 or 3 subglottic stenosis and 13 children who underwent a surgical procedure for subglottic stenosis. Sixty-seven children had a preoperative diagnosis of asthma, 62 were atopic and 78 had symptoms of gastro-oesophageal reflux. Oesophagoscopy was diagnostic of gastro-oesophageal reflux in 19 of 110 cases, and 106 children (45.1%) had bronchoscopic findings suggestive of GERD. Eight children had eosinophilic oesophagitis. After multivariate analysis, significantly abnormal bronchoscopy was significantly associated with chronic cough (P = 0.02), have a previous intubation (P = 0.002) or be younger than 3 years old (P = 0.01). CONCLUSION: Significant findings on bronchoscopy that warranted further surgical intervention were uncommon in this cohort. Nearly half of the patients had evidence of gastro-oesophageal reflux. In patients without risk factors for significant abnormalities, empiric medical management may be beneficial prior to endoscopy.

The association of cytochrome P450 genetic polymorphisms with sulfolane formation and the efficacy of a busulfan-based conditioning regimen in pediatric patients undergoing hematopoietic stem cell transplantation.

Cytochrome P450 enzymes (CYPs) and flavin-containing monooxygenases (FMOs) likely have a role in the oxidation of intermediate metabolites of busulfan (Bu). In vitro studies to investigate the involvement of these enzymes are cumbersome because of the volatile nature of the intermediate metabolite tetrahydrothiophene (THT) and the lack of sensitive quantitation methods. This study explored the association between the CYP2C9, CYP2C19, CYP2B6 and FMO3 genotypes and sulfolane (Su, a water soluble metabolite of Bu) plasma levels in children undergoing hematopoietic stem cell transplantation (HSCT). The relationship between these genotypes and the effectiveness of myeloablative conditioning was also analyzed. Sixty-six children receiving an intravenous Bu-based myeloablative conditioning regimen were genotyped for common functional variant alleles in CYP2C9 (*2 and *3), CYP2C19 (*2 and *17), FMO3 (rs2266780, rs2266782 and rs1736557) and CYP2B6 (*5 and *9). The plasma levels of Bu and its metabolite Su were measured after the ninth Bu dose in a subset of 44 patients for whom plasma samples were available. The ratio of Bu to Su was considered the metabolic ratio (MR) and was compared across the genotype groups. Higher MRs were observed in CYP2C9*2 and *3 allele carriers (mean±s.d.: 7.8±3.6 in carriers vs 4.4±2.2 in non-carriers; P=0.003). An increased incidence of graft failure was observed among patients with an MR>5 compared with those with MR values <5 (20% vs 0%; P=0.02). In contrast, a significantly higher incidence of relapse and graft failure (evaluated as event-free survival) was observed in patients with malignant disease who carried CYP2B6 alleles with reduced function on both chromosomes compared with carriers of at least one normal allele (100% vs 40%; P=0.0001). These results suggest that CYP2C9 has a role in the oxidation reactions of THT and indicate that it may be possible to predict the efficacy of Bu-based myeloablative conditioning before HSCT on the basis of CYP genotypes and Bu MRs.

[MEN for multiple endocrin neoplasms: When evokate MEN? Update 2022]. / Mise au point sur les néoplasies endocriniennes multiples.

Multiple endocrine neoplasia (MEN) are genetic predisposition syndromes to endocrine tumors including MEN1, MEN2 and exceptionally MEN4. MEN are transmitted in an autosomal dominant fashion with a high penetrance. Classically, there is no genotype/phenotype correlation for NEM1 whereas this is the case for NEM2. Patients with NEM1, linked to an inactivating mutation of the menin gene, may present with: primary hyperparathyroidism, pituitary adenoma, duodeno-pancreatic neuroendocrine tumors (NETs), bronchial tumors with an increased risk of thymoma, adrenal cortical tumors, an increased risk of breast cancer and characteristic skin involvement such as collagenomas, lentiginomas and an increased risk of skin cancer. These patients require at least annual follow-up. Screening of children is proposed from the age of 5 years. Patients with NEM2, linked to an activating mutation of the RET proto-oncogene, all present with medullary thyroid carcinoma (MTC) at a variable age depending on the genotype. Some patients present a pheochromocytoma (50 %) and hyperparathyroidism (20 %). Pediatric forms with aggressive CMT, ganglioneuromatosis and marfanoid syndrome exist (rare NEM2B). Some mutations are associated with a risk of aggressive CMT, justifying prophylactic thyroidectomy before 6 months of age. The age of genetic testing depends on the mutation subtype in the NEM2 parent. NEM4, related to a mutation in the CDKN1B gene, are rare, with a less well-known pathogenesis and their follow-up is not well codified.

Mind-body and art therapies impact on emotional regulation in patients with chronic diseases: a pragmatic mixed-methods randomized controlled trial.

BACKGROUND: Effective emotional regulation is recognized as essential to a good mental health of people with chronic diseases, and Mind-body and Art Therapies (MBATs) could have a positive effect on emotional regulation skills in this population. Thus, we aimed to evaluate the effect of MBATs on emotional regulation as measured by the Difficulties in Emotion Regulation Scale (DERS) questionnaire. METHODS: A convergent mixed approach nested in a pragmatic superiority two arms parallel randomized controlled trial was conducted. French speaking adults with one or more chronic somatic illnesses and not suffering from a chronic psychiatric disorder unrelated to one of their chronic somatic illness were included. At inclusion, non-directive interviews were conducted, followed by an initial DERS assessment. The same combination of evaluation was implemented after 6 months of activity (T1). After inclusion, each participant was randomized within either the intervention group (G1) or the control group (G2) following a controlled wait-list design by use of a pregenerated randomization list. Staff and patient were blinded to this list until the initial evaluation was completed, after which the trial was conducted in an open-label fashion. Participants chose 2 mediations: one creativity-focused (art-therapy, writing workshop, theatre of life, vocal workshop) and one mind-body-focused (mindfulness meditation, Pilates, shiatsu, ayurvedic massages). G1 started their mediations immediately after inclusion, while G2 started 6 months later. Primary outcome was the change in means at 6 months in the overall DERS score compared between each group. Non-directive interviews were carried out at the inclusion and after 6 months of MBATs. A continuous inductive analysis was carried out on gathered material in G1 to explore the participants' experiences regarding their disease and their perceived changes associated to the intervention. RESULTS: A total of 150 patients was randomized (75 per groups) at the end of the study. At T1, 133 patients filled out the final questionnaire (67 in G1 vs 66 in G2) and 112 interviews were analysed (54 in G1 vs 58 in G2). All 150 patients were analysed (intention to treat) using a multiple imputation approach. The mean DERS score at T0 was equal to 82.8 ± 21.1 and 85.0 ± 20.2 in G1 and G2 respectively. On average, at T1, the score decreased in the G1 (Δ = -4.8, SD = 21.3) and in G2 (Δ = -0.11, SD = 17.8). The difference in decrease, however, was not statistically significant (p = 0.13). Qualitative analysis underlined some MBATs benefits on emotional regulation, especially on regulation strategies. No harms related to the intervention has been observed. CONCLUSIONS: This study only partially supports benefits on MBAT on emotional regulation skills enhancement in patients with chronic disease receiving MBATs, as measured by the DERS scale. TRIAL REGISTRATION: The protocol was registered on Clinical Trials (NCT02911207).

First direct evidence of lion hunting and the early use of a lion pelt by Neanderthals.

During the Upper Paleolithic, lions become an important theme in Paleolithic art and are more frequent in anthropogenic faunal assemblages. However, the relationship between hominins and lions in earlier periods is poorly known and primarily interpreted as interspecies competition. Here we present new evidence for Neanderthal-cave lion interactions during the Middle Paleolithic. We report new evidence of hunting lesions on the 48,000 old cave lion skeleton found at Siegsdorf (Germany) that attest to the earliest direct instance of a large predator kill in human history. A comparative analysis of a partial puncture to a rib suggests that the fatal stab was delivered with a wooden thrusting spear. We also present the discovery of distal lion phalanges at least 190,000 old from Einhornhöhle (Germany), representing the earliest example of the use of cave lion skin by Neanderthals in Central Europe. Our study provides novel evidence on a new dimension of Neanderthal behavioral complexity.

Development of a positron probe for localization and excision of brain tumours during surgery.

The survival outcome of patients suffering from gliomas is directly linked to the complete surgical resection of the tumour. To help the surgeons to delineate precisely the boundaries of the tumour, we developed an intraoperative positron probe with background noise rejection capability. The probe was designed to be directly coupled to the excision tool such that detection and removal of the radiolabelled tumours could be simultaneous. The device consists of two exchangeable detection heads composed of clear and plastic scintillating fibres. Each head is coupled to an optic fibre bundle that exports the scintillating light to a photodetection and processing electronic module placed outside the operative wound. The background rejection method is based on a real-time subtraction technique. The measured probe sensitivity for (18)F was 1.1 cps kBq(-1) ml(-1) for the small head and 3.4 cps kBq(-1) ml(-1) for the large head. The mean spatial resolution was 1.6 mm FWHM on the detector surface. The gamma-ray rejection efficiency measured by realistic brain phantom modelling of the surgical cavity was 99.4%. This phantom also demonstrated the ability of the probe to detect tumour discs as small as 5 mm in diameter (20 mg) for tumour-to-background ratios higher than 3:1 and with an acquisition time around 4 s at each scanning step. These results indicate that our detector could be a useful complement to existing techniques for the accurate excision of brain tumour tissue and more generally to improve the efficiency of radio-guided cancer surgery.

Determination of ketamine and norketamine in plasma by micro-liquid chromatography-mass spectrometry.

A sensitive method of determination of ketamine and norketamine by micro-liquid chromatography/mass spectrometry was developed as part of a clinical trial in a pediatric population. Compounds were extracted from 100 microl plasma samples using solid-phase extraction on Oasis MCX cartridges. Separation was achieved on a C18 micro-column with a mobile phase composed of formic acid 0.1% and acetonitrile (90/10, v/v). Detection of ketamine, norketamine and their internal standard norketamine D4 was performed using selected ion monitoring at m/z 238.2, 224.2 and 228.2, respectively. Under these conditions, no loss of signal due to matrix effect was found and time of analysis did not exceed 10 min. Extracted calibration curves were linear from 5 to 500 ng/ml for each analyte, with correlation coefficients over 0.999. Intra- and inter-day validation studies showed mean recoveries between 98.1 and 101.7% and a relative standard deviation below 1.9%. Extraction recoveries ranged from 84.8 to 89.8% for both ketamine and norketamine. Limit of quantification was 4 ng/ml for each analyte.

First evidence of an extensive Acheulean large cutting tool accumulation in Europe from Porto Maior (Galicia, Spain).

We describe a European Acheulean site characterised by an extensive accumulation of large cutting tools (LCT). This type of Lower Paleolithic assemblage, with dense LCT accumulations, has only been found on the African continent and in the Near East until now. The identification of a site with large accumulations of LCTs favours the hypothesis of an African origin for the Acheulean of Southwest Europe. The lithic tool-bearing deposits date back to 293-205 thousand years ago. Our chronological findings confirm temporal overlap between sites with clear "African" Acheulean affinities and Early Middle Paleolithic sites found elsewhere in the region. These complex technological patterns could be consistent with the potential coexistence of different human species in south-western Europe during the Middle Pleistocene.

Cytotoxic T cell response against the chimeric ETV6-AML1 protein in childhood acute lymphoblastic leukemia.

Cytotoxic T lymphocytes (CTL) are potent effector cells that could provide long term antitumor immunity if induced by appropriate vaccines. CTL recognize 8-14 amino acid-long peptides processed intracellularly and presented by MHC class I molecules. A well-characterized example of a potential tumor antigen in childhood pre-B Acute Lymphoblastic Leukemia (ALL) results from the chromosomal translocation 12;21 leading to the fusion of the ETV6 and AML1 genes. This translocation is observed in > 25% of ALL-patients. In this study, we have examined whether the chimeric ETV6-AML1 protein could serve as a tumor specific antigen for CTL in HLA-A2.1 individuals. We have identified a nonapeptide (RIAECILGM), encoded by the fusion region of the ETV6-AML1 protein, that binds to HLA-A2.1 molecules and induces specific primary CTL in peripheral blood lymphocytes from healthy donors. These CTL specifically lysed HLA-A2.1 tumor cells endogeneously expressing the ETV6-AML fusion protein. CTL with similar functional capacities were found with high frequencies and cloned from one patient's bone marrow indicating that ETV6-AML1-specific anti-ALL CTL are, at least in some patients, spontaneously stimulated and might participate to host antileukemia defense.

[Subthalamic nucleus stimulation using a Fisher ZD stereotactic frame, MR-CT fusion guidance and peroperative orthogonal radiographs, in Parkinson disease]. / Evaluation de la stimulation du noyau sous-thalamique utilisant un cadre de Fischer adapté, un guidage par fusion IRM-scanner et un contrôle radiographique stéréotaxique peropératoire, dans la maladie de Parkinson.

BACKGROUND: We present the method and results of an original technique to implant electrodes in the subthalamic nucleus (STN) to treat Parkinson's disease, based on adaptations of the Fisher ZD stereotactic frame. METHODS: Targets coordinates were calculated after fusion of stereotactic CT-scan and MRI images. STN was localized by its theoretical coordinates according to AC-PC and by its direct visualization on T2 images. Electrodes were implanted after local anesthesia, using peroperative multicanal microrecordings and test stimulation. Electrodes location was checked by peroperative perpendicular radiographs. To avoid projection of the frame arm on the area of interest on anteroposterior and lateral radiographs, the arm was fixed at 45 degrees from the usual 90 degrees position. This original fixation needed a trigonometric transformation of the X and Y stereotactic coordinates. Radiopaque markers, fixed on the frame, were identified on the radiographs, allowing the calculation of the stereotactic coordinates of the electrode tip, which were then entered in the stereotactic MRI, to check its location from the defined target. RESULTS: No problem due to adaptations of the frame occurred in the 60 patients. In all cases, peroperative radiographs allowed to confirm the correct location of electrodes. Six months after surgery, UPDRS III score without medication was decreased by 52% with stimulation "on". UPDRS IV items 32, 33 and 39 scores were decreased by 75,7, 79,5 and 72%. Daily dopa-equivalent dose was decreased by 71%. One asymptomatic thalamic hematoma and two wound infections occurred. CONCLUSION: This method was efficient and safe to implant deep electrodes.

[Real life visual and anatomic outcomes of aflibercept treatment for treatment-naive patients with exudative age-related macular degeneration]. / Réponse visuelle et anatomique en condition de « vraie vie ¼ du traitement par aflibercept chez les patients naïfs atteints de dégénérescence maculaire liée à l'âge exsudative.

Anti-VEGF therapies have revolutionized the treatment of neovascular age-related macular degeneration (AMD). PURPOSE: The goal of this study was to evaluate the "real life" visual and anatomical outcomes of aflibercept treatment for treatment-naive patients with exudative AMD. METHODS: This was a retrospective study of patients treated with aflibercept in the department of Ophthalmology at the University Hospital of Bordeaux between November 2013 and July 2015. The follow-up period varied from 3months to 2years. All patients received an induction phase with 3monthly intravitreal injections (IVT) followed by personalized monitoring. ETDRS best-corrected visual acuity (BCVA), fundus examination and OCT were performed at each visit. Data were collected at day 0, 3 months, 6, 9, 12months, 18 and 24months. RESULTS: Forty-three eyes of forty patients, mean age 77.7years, were included, with a minimum of 3months follow-up. Twenty-five eyes were followed for 1year; 5 eyes for two years. At baseline, the mean BCVA was 55.7 letters. Patients received 7.5 injections on average the first year and 2.6 the 2nd year. The mean gain of visual acuity was +7.3 letters at 3 months, +6.2 letters at 12 months, and +6.8 letters at 2years. Anatomically, the OCT data showed a decline of all parameters. The central macular thickness decreased by 118.3µm at 3months, 136.4µm at 12months and 65.5µm at 2years. CONCLUSION: Aflibercept can achieve effective visual and anatomical outcomes with results, which approach the pivotal studies, despite the use of personalized protocols and longer monitoring intervals.

When should ultrasonography be used to detect asymptomatic carotid atheroma in diabetic patients?

INTRODUCTION: While guidelines for detection of silent myocardial and lower limb ischemia are established, data on screening asymptomatic carotid lesions remain scarce. However, such screening would be costly. Since the prevalence of diabetes increases constantly, it is necessary to keep screening costs low by setting up criteria for the selection of patients at risk of ischemic cerebral attack and those who will need medical or surgical attention. Diabetic patients, particularly type 2, often have many reasons to take anti-platelet agents and lipid-lowering therapy. Therefore, carotid ultrasonography screening would have little effect on treatment modification or on glycaemia and blood pressure objectives, but could improve the prognosis of operable lesions. IN THE GENERAL POPULATION: A one-time screening program was considered worthwhile if the prevalence of severe asymptomatic stenosis was over 20%. The presence of another arterial occlusive disease or other cardio-vascular risk factors could be a major argument for screening. IN DIABETIC PATIENTS: Carotid intima-media thickness (IMT) was recognized as a reliable prognostic indicator of heart attack and stroke. It worsens with duration of diabetes, renal failure, cardiac neuropathy and poor long term glycaemic control. CONCLUSION: Our review suggests that a one-time carotid ultrasonography screening could be recommended for diabetic patients with coronary disease or lower limb atherosclerosis (secondary prevention), all diabetic patients above 60 years of age, smokers, hypertensive and with hypercholesterolemia; type 1 diabetic patients with poor long term glycaemic control; all type 2 diabetic patients with renal failure, a long duration of ill-controlled diabetes or with a carotid bruit. This literature review should be analyzed with caution. It would be helpful to organize a prospective long term study on all types of diabetic patients, including a carotid ultrasonography screening program by experienced radiologists.

Influence of glutathione S-transferase gene polymorphisms on busulfan pharmacokinetics and outcome of hematopoietic stem-cell transplantation in thalassemia pediatric patients.

Hematopoietic stem-cell transplantation (HSCT) is currently the only curative therapeutic option for the treatment of thalassemia. In spite of the high cure rate, HSCT can lead to life-threatening adverse events in some patients. Busulfan (Bu) is a key component of the conditioning regimen prior to HSCT. Inter-individual differences in Bu pharmacokinetics (PK) are hypothesized to influence Bu efficacy and toxicity. Since Bu is mainly metabolized by glutathione S-transferase (GST), we investigated the relationship of GSTA1 and GSTM1 genotypes with first-dose PK and HSCT outcomes in 44 children with thalassemia intermedia and thalassemia major. All children received a myeloablative conditioning regimen with IV Bu. Association analysis revealed a relationship between GSTA169C>T (or haplotype *A/*B) and first Bu dose PK that was dependent on sex and Pesaro risk classification (PRC). Among female patients and patients with PRC I-II, homozygous individuals for the GSTA1T-69 allele defining haplotype *B, had higher Bu exposure and lower clearance (P⩽0.01). Association with HSCT outcomes showed that patients with the GSTM1 null genotypes had higher occurrence of regimen-related toxicity (P=0.01). These results suggest that GST genotypes could be useful to tailor the first Bu dose accordingly to improve HSCT outcome.

Genetic Diversification and Dispersal of Taro (Colocasia esculenta (L.) Schott).

Taro (Colocasia esculenta (L.) Schott) is widely distributed in tropical and sub-tropical areas. However, its origin, diversification and dispersal remain unclear. While taro genetic diversity has been documented at the country and regional levels in Asia and the Pacific, few reports are available from Americas and Africa where it has been introduced through human migrations. We used eleven microsatellite markers to investigate the diversity and diversification of taro accessions from nineteen countries in Asia, the Pacific, Africa and America. The highest genetic diversity and number of private alleles were observed in Asian accessions, mainly from India. While taro has been diversified in Asia and the Pacific mostly via sexual reproduction, clonal reproduction with mutation appeared predominant in African and American countries investigated. Bayesian clustering revealed a first genetic group of diploids from the Asia-Pacific region and to a second diploid-triploid group mainly from India. Admixed cultivars between the two genetic pools were also found. In West Africa, most cultivars were found to have originated from India. Only one multi-locus lineage was assigned to the Asian pool, while cultivars in Madagascar originated from India and Indonesia. The South African cultivars shared lineages with Japan. The Caribbean Islands cultivars were found to have originated from the Pacific, while in Costa Rica they were from India or admixed between Indian and Asian groups. Taro dispersal in the different areas of Africa and America is thus discussed in the light of available records of voyages and settlements.

Contribution of single-photon emission computed tomography in the diagnosis and follow-up of CNS toxicity of a cytarabine-containing regimen in pediatric leukemia.

PURPOSE: Cytarabine (ara-C) is one of the most effective chemotherapeutic agents in patients with acute leukemia (AL), with a clear dose effect. Use of high-dose ara-C is hampered, however, by a noticeable toxicity, particularly to the CNS. We investigated the usefulness of CNS perfusion imaging with technetium-99m ((99m)Tc)-hexamethyl-propylene-amine oxime (HMPAO) single-photon emission computed tomography (SPECT) concurrent to magnetic resonance imaging (MRI) to specifically assess the effects of standard- and high-dose ara-C in children with AL. PATIENTS AND METHODS: Twenty-six perfusion studies using (99m)Tc-HMPAO SPECT were performed in 12 children (age range, 4 to 15 years) with AL after induction therapy, which consisted of a standard-dose ara-C, immediately after consolidation with high-dose ara-C, and later during follow-up (range, 6 to 44 months). The chemotherapy-related adverse events were monitored and correlated to SPECT and MRI. RESULTS: After the induction phase, all children were neurologically normal on MRI. On SPECT imaging, four children displayed a slightly heterogeneous perfusion. After high-dose ara-C (4 to 36 g/m(2)), five children had regressive neurologic signs of potential toxic origin. Of these five children, only one had an abnormal MRI scan, whereas all patients showed evidence of diffuse cerebral and/or cerebellar heterogeneous perfusion on SPECT. The seven other patients without any neurologic symptoms had normal MRI scans; SPECT was normal for three patients and abnormal for four patients. On follow-up, for four children who had presented with clinical neurologic toxicity, SPECT improved in three patients and remained unchanged in one patients. In two of these four children, delayed abnormalities (T2 white matter hypersignal and cerebellar atrophy) appeared on MRI scans. CONCLUSION: In our series, diffuse heterogeneous brain hypoperfusion is often the sole early objective imaging feature identified by SPECT of high-dose ara-C neurotoxicity, where MRI still demonstrates normal pictures.

Mapping of chromosome 20 for loss of heterozygosity in childhood ALL reveals a 1,000-kb deletion in one patient.

The long arm of chromosome 20 displays recurrent loss of heterozygosity (LOH) for microsatellite markers in blast cells from children with acute lymphoblastic leukemia. To further characterize the region of deletion and to precisely establish its frequency, we searched for LOH in 103 children with ALL using polymorphic markers in the previously described region of interest, namely between D20S101 and D20S887. LOH was detected in nine patients (ie with a frequency of 8.7%). Interestingly, in one patient, a small deletion was found, flanked proximally by D20S850 and distally by M201, a dinucleotide repeat identified from chromosome 20 sequences. The distance between these two markers is approximately 1000 kb. The occurrence of non-random deletions of the long arm of chromosome 20 has previously been observed in myeloid malignancies (myeloproliferative disorders and myelodysplastic syndromes) in 5-10% of patients. The small deletion in our patient is located within the common region of deletion of myeloproliferative disorders suggesting that a tumor suppressor gene may be the common target of the deletions in various types of hematological malignancies.