Impact of renal impairment on dihydropyrimidine dehydrogenase (DPD) phenotyping.

BACKGROUND: The chemotherapeutic agent 5-fluorouracil (5-FU) is catabolized by dihydropyrimidine dehydrogenase (DPD), the deficiency of which may lead to severe toxicity or death. Since 2019, DPD deficiency testing, based on uracilemia, is mandatory in France and recommended in Europe before initiating fluoropyrimidine-based regimens. However, it has been recently shown that renal impairment may impact uracil concentration and thus DPD phenotyping. PATIENTS AND METHODS: The impact of renal function on uracilemia and DPD phenotype was studied on 3039 samples obtained from three French centers. We also explored the influence of dialysis and measured glomerular filtration rate (mGFR) on both parameters. Finally, using patients as their own controls, we assessed as to what extent modifications in renal function impacted uracilemia and DPD phenotyping. RESULTS: We observed that uracilemia and DPD-deficient phenotypes increased concomitantly to the severity of renal impairment based on the estimated GFR, independently and more critically than hepatic function. This observation was confirmed with the mGFR. The risk of being classified 'DPD deficient' based on uracilemia was statistically higher in patients with renal impairment or dialyzed if uracilemia was measured before dialysis but not after. Indeed, the rate of DPD deficiency decreased from 86.4% before dialysis to 13.7% after. Moreover, for patients with transient renal impairment, the rate of DPD deficiency dropped dramatically from 83.3% to 16.7% when patients restored their renal function, especially in patients with an uracilemia close to 16 ng/ml. CONCLUSIONS: DPD deficiency testing using uracilemia could be misleading in patients with renal impairment. When possible, uracilemia should be reassessed in case of transient renal impairment. For patients under dialysis, testing of DPD deficiency should be carried out on samples taken after dialysis. Hence, 5-FU therapeutic drug monitoring would be particularly helpful to guide dose adjustments in patients with elevated uracil and renal impairment.

Treatment of micropollutants in wastewater: Balancing effectiveness, costs and implications.

In this contribution, we analyse scenarios of advanced wastewater treatment for the removal of micropollutants. By this we refer to current mainstream, broad spectrum processes including ozonation and sorption onto activated carbon. We argue that advanced treatment requires properly implemented tertiary (nutrient removal) treatment in order to be effective. We review the critical aspects of the main advanced treatment options, their advantages and disadvantages. We propose a quantification of the costs of implementing advanced treatment, as well as upgrading plants from secondary to tertiary treatment when needed, and we illustrate what drives the costs of advanced treatment for a set of standard configurations. We propose a cost function to represent the total costs (investment, operation and maintenance) of advanced treatment. We quantify the implications of advanced treatment in terms of greenhouse gas emissions. Based on the indicators of total toxic discharge, toxicity at the discharge points and toxicity across the stream network discussed in Pistocchi et al. (2022), we compare costs and effectiveness of different scenarios of advanced treatment. In principle the total toxic load and toxicity at the points of discharge could be reduced by about 75 % if advanced treatment processes were implemented virtually at all wastewater treatment plants, but this would entail costs of about 4 billion euro/year for the European Union as a whole. We consider a "compromise" scenario where advanced treatment is required at plants of 100 thousand population equivalents (PE) or larger, or at plants between 10 and 100 thousand PE if the dilution ratio at the discharge point is 10 or less. Under this scenario, the length of the stream network exposed to high toxicity would not increase significantly compared to the previous scenario, and the other indicators would not deteriorate significantly, while the costs would remain at about 1.5 billion Euro/year. Arguably, costs could be further reduced, without a worsening of water quality, if we replace a local risk assessment to generic criteria of plant capacity and dilution in order to determine if a WWTP requires advanced treatment.

Numerical modelling of the suspended particulate matter dynamics in a regulated river network.

Understanding and predicting the propagation, deposition and resuspension of suspended particulate matter (SPM) in river networks is important for managing water resources, ecological habitat, pollution, navigation, hydropower generation, reservoir sedimentation, etc. Observational data are scarce and costly, and there is little feedback on the efficiency of numerical simulation tools for compensating the lack of data on a river scale of several hundreds of kilometers. This paper aims at exploring the use of a one-dimensional (1-D) hydrodynamical model for understanding the source and fate of SPM during complex events. The numerical model was applied to the May-June 2008 flood in the Lower Rhône River, France. This event was a combination of floods of the Isère (including dam flushing operations in the Lower Isère River) and Durance tributaries over a two-week period. The simulation code was used to model the SPM fluxes at a high spatial and temporal resolution using a multi-class approach. Approximately half of the 4.9 Mt of SPM measured at the outlet at Beaucaire were found to come from the Isère River and the other half from the Durance River, whereas previous studies estimated that most of the SPM flux at the outlet came from the Durance River. The amount of SPM trapped within the river network, mainly behind the first hydropower structure downstream of the Isère confluence, was estimated to be 3.7 Mt due to the deposition of the coarsest particles. Such a model proved to be able to compute the interaction of various grain size classes with dams and other structures. In turn, the quality of the results of SPM fluxes and deposition is highly sensitive to particle parameters, especially grain size distribution, and to the operational rules of reservoirs.

Sampling of suspended particulate matter using particle traps in the Rhône River: Relevance and representativeness for the monitoring of contaminants.

Monitoring hydrophobic contaminants in surface freshwaters requires measuring contaminant concentrations in the particulate fraction (sediment or suspended particulate matter, SPM) of the water column. Particle traps (PTs) have been recently developed to sample SPM as cost-efficient, easy to operate and time-integrative tools. But the representativeness of SPM collected with PTs is not fully understood, notably in terms of grain size distribution and particulate organic carbon (POC) content, which could both skew particulate contaminant concentrations. The aim of this study was to evaluate the representativeness of SPM characteristics (i.e. grain size distribution and POC content) and associated contaminants (i.e. polychlorinated biphenyls, PCBs; mercury, Hg) in samples collected in a large river using PTs for differing hydrological conditions. Samples collected using PTs (n = 74) were compared with samples collected during the same time period by continuous flow centrifugation (CFC). The grain size distribution of PT samples shifted with increasing water discharge: the proportion of very fine silts (2-6 µm) decreased while that of coarse silts (27-74 µm) increased. Regardless of water discharge, POC contents were different likely due to integration by PT of high POC-content phytoplankton blooms or low POC-content flood events. Differences in PCBs and Hg concentrations were usually within the range of analytical uncertainties and could not be related to grain size or POC content shifts. Occasional Hg-enriched inputs may have led to higher Hg concentrations in a few PT samples (n = 4) which highlights the time-integrative capacity of the PTs. The differences of annual Hg and PCB fluxes calculated either from PT samples or CFC samples were generally below 20%. Despite some inherent limitations (e.g. grain size distribution bias), our findings suggest that PT sampling is a valuable technique to assess reliable spatial and temporal trends of particulate contaminants such as PCBs and Hg within a river monitoring network.

Leflunomide for BKvirus: Report of Seven Kidney-Transplanted Children.

BACKGROUND: Leflunomide is an immunosuppressive agent commercialized for treatment of rheumatoid arthritis. Because of its immunosuppressive and possible antiviral properties, leflunomide has been evaluated in some case series of BKVAN with favorable results, mostly in adult patients. Leflunomide targeted levels are usually between 50 and 100 mg/L in kidney transplant adult patients. Data in pediatric population are scarce. OBJECTIVE: To assess the effect of leflunomide on BKvirus in kidney-transplanted children. METHODS: Therapeutic drug monitoring of leflunomide is routinely performed by measuring its active metabolite, teriflunomide, using a simple HPLC-UV method. Pediatric kidney transplant patients with at least one teriflunomide sample between 2010 and 2017 were retrospectively included in this study. Viremia control was defined as undetectable BK viremia or a decrease of more than 1 log in the viral load from the baseline after two months of treatment. Adverse events were recorded. RESULTS: A total of 7 patients from 3 centers was included. 6 were only kidney transplant recipients; 1 was a lung-kidney transplant recipient with cystic fibrosis. All patients reported high load BK viremia but none developed BKVAN. For 67% of the patients, complete BK viral clearance was observed during leflunomide treatment with drastic immunosuppressive therapy reduction. Mycophenolate was indeed discontinued in almost all patients. Of note, leflunomide concentrations were significantly higher when viremia was controlled. Only 33% of the observed concentrations were >40 mg/L. The patient with cystic fibrosis had lower concentrations with higher drug doses. No hepatotoxicity was observed in this study and no patient experienced graft rejection. Leflunomide was suspected to cause hemolytic anemia and one patient experienced biological pancreatitis. CONCLUSION: This study evidenced the wide interindividual variability of the exposure and supported the routine practice of leflunomide with a suggested target level of 30-40 mg/L in pediatric kidney transplanted patient. However, because of the very limited number of patients in our series, further investigations are needed to validate this suggestion.

[Neurotrophic keratitis after vitrectomy and circumferential endophotocoagulation for retinal detachment]. / Kératite neurotrophique après chirurgie du décollement de rétine par vitrectomie et endophotocoagulation circonférentielle.

INTRODUCTION: Circumferential (360°) endophotocoagulation is frequently implemented during vitrectomies for retinal detachment. This photocoagulation may result in neurotrophic keratitis by damaging the ciliary nerves in the suprachoroidal space on their way to the pupil. We report a series of 4 cases of neurotrophic keratitis following a circumferential endophotocoagulation. PATIENTS AND METHODS: A retrospective observational case series of 4 non-diabetic patients having presented with a neurotrophic keratitis following a retinal detachment treated with vitrectomy and circumferential endophotocoagulation (532 nm) at Caen University Hospital. We report the various forms of corneal lesions and the diagnostic criteria allowing for the diagnosis of neurotrophic keratitis. DISCUSSION: Neurotrophic keratitis is caused by lesions occurring at various levels of corneal innervation. Endophotocoagulation may cause a neurotrophic keratitis by damaging the short and long ciliary nerves on their way to the pupil in the suprachoroidal space. The sequelae of this condition can limit visual recovery. Hence, it is probably advisable to screen for corneal anesthesia or severe hypesthesia following a retinal detachment treated with vitrectomy and circumferential endophotocoagulation and to implement prophylactic treatment (intensive lubricant therapy; preservative-free eye drops) if needed. CONCLUSION: The risk of neurotrophic keratitis should be weighed against the dose of laser retinopexy necessary and sufficient to obtain a sustained retinal reattachment. If circumferential endophotocoagulation is implemented, it is probably sensible to monitor corneal sensitivity and to adapt postoperative treatment if necessary.

[Efficacy of autologous peripheral blood stem cell transplantation (auto-PBSCT) on the neuropathic manifestations in POEMS syndrome]. / Efficacité à moyen terme de l'autogreffe de cellules souches hématopoïétiques périphériques sur la polyneuropathie du syndrome POEMS: expérience chez 5 cas.

INTRODUCTION: POEMS syndrome (polyneuropathy, organomegaly, endocrynopathy, M-protein, and skin changes) is a rare multisystem disease associated with plasma cell dyscrasia. The efficacy of autologous peripheral blood stem cell transplantation (auto-PBSCT) reported in case series has been mainly based on hematologic criteria and clinical recovery of peripheral neuropathy dysfunctions but has not been specifically evaluated. This retrospective study aimed to analyze the efficacy of auto-PBSCT on disability and electrophysiological patterns in patients with POEMS syndrome. METHODS: Five patients presenting with POEMS syndrome received auto-PBSCT. Disability was evaluated before treatment and at 6 and 12 months using the Overall Neuropathy Limitation Scale (ONLS) and MRC sumscore of 28 muscles. Nerve conduction studies were performed before and one year after treatment, on median, ulnar, fibular and tibial nerves. RESULTS: Mean age was 60.6 years (49-70). Disease duration between first symptoms and auto-PBSCT was 15.4 months (2-33). Before auto-PBSCT, mean ONLS score was 4.2 (1-10) and mean MRC sumscore 115.8/140 (74-140). At M6, mean ONLS score decreased and mean MRC sumscore increased; both were improved in all patients at M12: mean ONLS score 3 (range 0-8) at M6 and 2.2 (range 0-7) at M12; mean MRC sumscore 118/140 (77-140) at M6 and 122.4/140 (80-140) at M12. Significant recovery in electrophysiological patterns was observed in all patients on ulnar and median nerves: before-after treatment differences were observed for motor conduction velocities (34.41 vs. 45.47 m/s; P<0.001), distal CMAP amplitudes (5.04 vs. 5.96 mV; P=0.004), and sensory conduction velocities (43.20 vs. 49.20 m/s; P=0.001). Distal CMAP amplitude remained low in fibular and tibial nerves (0.41 vs. 0.17 mV). CONCLUSIONS: Clinical and electrophysiological improvement is obvious in POEMS syndrome peripheral neuropathy within one year after treatment with auto-PBSCT, undoubtedly resulting from extensive remyelinisation and axonal regeneration. Further studies are required to examine long-term outcome in patients with POEMS syndrome given auto-PBSCT.

[Identifying addictive behaviors among adolescents: a school-based survey]. / Repérer les comportements addictifs chez les adolescents : enquête en milieu lycéen.

French epidemiological data show that adolescents today experiment with tobacco at an earlier age than in the 1990s. Half of them combine tobacco consumption with other psychoactive products such as alcohol or cannabis. Tobacco consumption usually begins in adolescence and early smoking initiation is related to stronger nicotine dependence and problems quitting in adulthood. Occasional tobacco consumption rapidly leads to nicotine dependence. The national smoking cessation questionnaire is a tool to assess addictive behaviors among adolescents. It includes validated scales such as the loss of autonomy over tobacco and psychological evaluation. The aim of this school-based study was to assess addictive behaviors among adolescents (specifically loss of autonomy over tobacco) and psychological profile. Data were collected from a cross-sectional study conducted in a high school in the Paris metropolitan area (Nogent-sur-Marne) in 2007 by the smoking cessation team of the Albert-Chenevier Hospital. Three hundred adolescents filled in a questionnaire concerning tobacco, alcohol, and cannabis consumption as well as their psychological profile. Loss of autonomy over tobacco use was evaluated with the Hooked on Nicotine Checklist (HONC). Anxiety and depressive disorders were identified using the Hospital Anxiety and Depression scale (HAD). Self-administered questionnaires were anonymously completed in the classroom by 151 girls and 149 boys aged 15-16 years (mean, 15.4 years): 34% of the adolescents smoked and most of them smoked at least one cigarette a day; 38% had used cannabis at least once in their life and one-third of them smoked more than 10 cannabis joints per month. Adolescents who frequently smoked cannabis had started smoking tobacco earlier than the other smokers (mean, 11.7 years versus 13.2 years). Adolescents often used different tobacco products. Manufactured cigarettes were the most frequently used, followed by shisha (waterpipe) and hand-rolled cigarettes. Among those who only smoked shisha, 76% had declared being non-smokers. Alcohol was the first psychoactive drug experimented by these adolescents; 73% had used alcohol at least once in their life and 10% used alcohol several times a week. According to the HONC, 94% of the smokers had lost control of their tobacco consumption. Concerning anxiety and depressive disorders, anxiety and depression scores were higher among smokers than non-smokers. Less than 6% of never-smokers had a depression score greater than 8 compared to 26% of adolescents smoking cannabis more than 10 times a month. The rapidity of the loss of autonomy among young smokers emphasizes the need for early interventions for tobacco prevention and cessation among adolescents. Tobacco use was often associated with anxiety and depressive symptoms, suggesting a need for professional support. The national smoking cessation questionnaire may be helpful in pediatric wards and consultations.

[Clinical, radiographic, prognostic and therapeutic aspects of demelinating disease with tumefactive demyelinating lesions]. / Aspects cliniques, radiologiques, pronostiques et thérapeutiques des lésions démyélinisantes extensives.

BACKGROUND: Demyelinating diseases presenting with a tumefactive demyelinating lesion (TDL) raise questions about classification, diagnosis, prognosis, and treatment. Their long-term course is not well described in literature. PATIENTS/METHODS: In a retrospective study, we describe the main characteristics of 29 patients with TDLs. In a case control study, we compared two cohorts of multiple sclerosis (MS) patients: 24 MS patients with TDL versus a reference cohort of patients with relapsing remitting MS. We compared the extended disability status score (EDSS) concerning the first demyelinating event (DE) with TDL, EDSS score at the end of follow-up and treatment intake. The objective was to discuss the prognosis and the management of TDL. RESULTS: In our study, the prognosis was better for patients with non-prevalent TDL (first DE without TDL) compared with patients with prevalent TDL (first DE with TDL) and was not different compared with the MS reference cohort. At the end of follow-up, there was no significant difference between patients treated with immunosuppressors after a first DE with TDL and patients with classical MS. The EDSS at the end of follow-up was statistically more severe for untreated patients after a first DE with TDL than for classical MS patients (P=0.0047). DISCUSSION: The prognosis of patients with TDL is difficult to assess because of its multifactorial nature (underlying disease and treatment impact). In our cohort, outcome of MS patients whose first severe DE involved a TDL was better when they received an early immunosuppressive treatment.

Comparative evaluation of in vitro parameters of tamoxifen citrate loaded poly(lactide-co-glycolide), poly(epsilon-caprolactone) and chitosan nanoparticles.

Tamoxifen (TAM), the clinical choice for the antiestrogen treatment of advanced or metastatic breast cancer, was formulated in nanoparticulate carrier systems in the form of poly(lactide-co-glycolide) (PLGA), poly-epsilon-caprolactone (PCL) and chitosan (CS) nanoparticles. The PLGA and PCL nanoparticles were prepared by a nanoprecipitation technique whereas the CS nanoparticles were prepared by the ionic gelation method. Mean particle sizes were under 260 nm for PLGA and PCL nanoparticles and around 400 nm for CS nanoparticles. Polydispersity indices were less than 0.4 for all formulations. Zeta potential values were positive for TAM loaded nanoparticles because of the positive charge of the drug. Drug loading values were significantly higher for PCL nanoparticles when compared to PLGA and CS nanoparticles. All nanoparticle formulations exhibited controlled release properties. These results indicate that TAM loaded PLGA, PCL and CS nanoparticles may provide promising carrier systems for tumor targeting.

Comparison of five organic wastes regarding their behaviour during composting: part 1, biodegradability, stabilization kinetics and temperature rise.

This paper aims to compare household waste, separated pig solids, food waste, pig slaughterhouse sludge and green algae regarding their biodegradability, their stabilization kinetics and their temperature rise during composting. Three experiments in lab-scale pilots (300 L) were performed for each waste, each one under a constant aeration rate. The aeration rates applied were comprised between 100 and 1100 L/h. The biodegradability of waste was expressed as function of dry matter, organic matter, total carbon and chemical oxygen demand removed, on one hand, and of total oxygen consumption and carbon dioxide production on the other. These different variables were found closely correlated. Time required for stabilization of each waste was determined too. A method to calculate the duration of stabilization in case of limiting oxygen supply was proposed. Carbon and chemical oxygen demand mass balances were established and gaseous emissions as carbon dioxide and methane were given. Finally, the temperature rise was shown to be proportional to the total mass of material biodegraded during composting.

Comparison of five organic wastes regarding their behaviour during composting: part 2, nitrogen dynamic.

This paper aimed to compare household waste, separated pig solids, food waste, pig slaughterhouse sludge and green algae regarding processes ruling nitrogen dynamic during composting. For each waste, three composting simulations were performed in parallel in three similar reactors (300 L), each one under a constant aeration rate. The aeration flows applied were comprised between 100 and 1100 L/h. The initial waste and the compost were characterized through the measurements of their contents in dry matter, total carbon, Kjeldahl and total ammoniacal nitrogen, nitrite and nitrate. Kjeldahl and total ammoniacal nitrogen and nitrite and nitrate were measured in leachates and in condensates too. Ammonia and nitrous oxide emissions were monitored in continue. The cumulated emissions in ammonia and in nitrous oxide were given for each waste and at each aeration rate. The paper focused on process of ammonification and on transformations and transfer of total ammoniacal nitrogen. The parameters of nitrous oxide emissions were not investigated. The removal rate of total Kjeldahl nitrogen was shown being closely tied to the ammonification rate. Ammonification was modelled thanks to the calculation of the ratio of biodegradable carbon to organic nitrogen content of the biodegradable fraction. The wastes were shown to differ significantly regarding their ammonification ability. Nitrogen balances were calculated by subtracting nitrogen losses from nitrogen removed from material. Defaults in nitrogen balances were assumed to correspond to conversion of nitrate even nitrite into molecular nitrogen and then to the previous conversion by nitrification of total ammoniacal nitrogen. The pool of total ammoniacal nitrogen, i.e. total ammoniacal nitrogen initially contained in waste plus total ammoniacal nitrogen released by ammonification, was calculated for each experiment. Then, this pool was used as the referring amount in the calculation of the rates of accumulation, stripping and nitrification of total ammoniacal nitrogen. Separated pig solids were characterised by a high ability to accumulate total ammoniacal nitrogen. Whatever the waste, the striping rate depended mostly on the aeration rate and on the pool concentration in biofilm. The nitrification rate was observed as all the higher as the concentration in total ammoniacal nitrogen in the initial waste was low. Thus, household waste and green algae exhibited the highest nitrification rates. This result could mean that in case of low concentrations in total ammoniacal nitrogen, a nitrifying biomass was already developed and that this biomass consumed it. In contrast, in case of high concentrations, this could traduce some difficulties for nitrifying microorganisms to develop.

[Anti-MAG paraproteinemic demyelinating polyneuropathy: a clinical, biological, electrophysiological and anatomopathological descriptive study of a 13-patients' cohort]. / Les polyneuropathies avec IgM monoclonale anti-MAG : étude descriptive clinique, biologique, électrophysiologique et anatomopathologique d'une cohorte de 13 patients.

INTRODUCTION: Polyneuropathies associated with IgM paraproteinemia and anti-myelin associated glycoprotein (MAG) antibodies (MAG-PN) have to be differentiated from chronic inflammatory demyelinating polyneuropathies. METHODS: In a retrospective study, we have analyzed clinical, electrophysiological, biological and pathological data from MAG-PN patients. RESULTS: Seven male and six female patients were followed in the department for a mean 2 years (0.5-6.5 years). Mean age at diagnosis was 61 years (44.5-85.5 years). Patients had symmetrical bilateral paresthesia (11/13) and hypoesthesia (11/13) prominent in the lower limbs. Nine patients developed gait ataxia and four patients had moderate distal weakness in the lower limbs. Mean Overall Neuropathy Limitation Scale was 2.3 (0-5). Nerve conduction study showed demyelinating features though delayed distal motor latency on median (206 % of normal value) and ulnar nerves (150% of normal value). Seven out of thirteen patients had at least two nerves with terminal latency index below 0.25. IgM paraproteinemia was of undetermined significance in ten cases and three patients had non-Hodgkin lymphoma. IgM deposits and widening of the peripheral myelin were observed in 5/7 sural nerve biopsies. Anti-MAG antibodies were detected in the sera of all patients using enzyme-linked immunosorbent assay and in 8/12 patients using western blot analysis. CONCLUSIONS: MAG-PN have distinctive clinical, electrophysiological and pathological features. It is a chronic, slowly progressive, predominantly sensory and ataxic neuropathy. Disability is usually moderate. Electrophysiological study shows distal demyelinating process and is highly suggestive of MAG-PN in more than one half of our patients. Several techniques may detect anti-MAG antibodies, they have to be associated to improve sensitivity and specificity of the test.

[Paraneoplastic limbic encephalitis with positive anti-RI antibodies and mediastinal seminoma]. / Encéphalite limbique paranéoplasique avec anticorps anti-RI et séminome médiastinal.

We report the case of a 49-year-old man who was admitted for progressive behaviorial disorders with frontal elements. There was no sensorial nor motor deficiency. Clinical examination revealed android obesity, cutaneous and mucous paleness, pubic and axillary depilation and gynecomastia. Encephalic MRI found a lesion of the left amygdalian region with high T2 intensity and low T1 intensity associated with gadolinium-enhancement. Cerebrospinal fluid analysis showed a lymphocytic meningitis. Panhypopituitarism was found on the endocrine investigations. Anti-RI antibodies were positive, leading to the diagnosis of paraneoplastic limbic encephalitis. The CT-scan showed a node of the lower part of the thymic area. Surgical resection revealed an ectopic mediastinal seminoma. The evolution consisted of paraneoplastic fever and crossed-syndrome with right hemiparesia and left common oculomotor nerve paralysis. Treatment was completed by two cycles of carboplatin, corticosteroids and substitutive opotherapy. Paraneoplastic fever disappeared, but behavioral disorders and palsy remain unchanged. The patient died two years later in a bedridden state. This case of paraneoplastic limbic encephalitis associated with positive anti-RI antibodies and mediastinal seminoma is exceptional and has not to our knowledge been described in the literature. Cancers usually associated with anti-RI antibody are breast and lung cancer. Paraneoplastic limbic encephalitis is not the classical clinical presentation, which usually is brainstem encephalitis. Hypothalamic involvement, uncommon in paraneoplastic limbic encephalitis is mainly associated with positive antineuronal anti-Ma2 antibodies. Finally, the gadolinium enhancement on encephalic MRI is unusual in paraneoplastic limbic encephalitis.

Evaluation of the impact of various agricultural practices on nitrate leaching under the root zone of potato and sugar beet using the STICS soil-crop model.

The quaternary aquifer of Vitoria-Gasteiz (Basque Country, Northern Spain) is characterised by a shallow water table mainly fed by drainage water, and thus constitutes a vulnerable zone in regards to nitrate pollution. Field studies were performed with a potato crop in 1993 and a sugar beet crop in 2002 to evaluate their impact on nitrate leaching. The overall predictive quality of the STICS soil-crop model was first evaluated using field data and then the model was used to analyze dynamically the impacts of different crop management practices on nitrate leaching. The model was evaluated (i) on soil nitrate concentrations at different depths and (ii) on crop yields. The simulated values proved to be in satisfactory agreement with measured values. Nitrate leaching was more pronounced with the potato crop than with the sugar beet experiment due to i) greater precipitation, ii) lower N uptake of the potato crop due to shallow root depth, and iii) a shorter period of growth. The potato experiment showed that excessive irrigation could significantly increase nitrate leaching by increasing both drainage and nitrate concentrations. The different levels of N-fertilization examined in the sugar beet study had no notable effects on nitrate leaching due to its high N uptake capacity. Complementary virtual experiments were carried out using the STICS model. Our study confirmed that in vulnerable zones agricultural practices must be adjusted, that is to say: 1) N-fertilizer should not be applied in autumn before winter crops; 2) crops with low N uptake capacity (e.g. potatoes) should be avoided or should be preceded and followed by nitrogen catch crops or cover crops; 3) the nitrate concentration of irrigation water should be taken into account in calculation of the N-fertilization rate, and 4) N-fertilization must be precisely adjusted in particular for potato crops.

Botulinum toxin injection in patients with hereditary spastic paraparesis.

In an open label study, we analyzed the efficacy of botulinum toxin injection at the lower limbs of patients with hereditary spastic paraparesis (HSP). Fifteen patients who showed disabling spasticity with no or poor effect of oral treatment were recruited consecutively. Botulinum toxin was injected (400 U; Botox) into the spastic muscles identified by clinical examination (equinus, varus, and pathological hip adduction). Patients were regularly assessed from the first day to the fifth month: spasticity (Ashworth), motor strength, range of movements, Functional Ambulation Categories (FAC), gait parameter, Rivermead Motor Assessment, self-analysis of benefit and satisfaction. We observed a moderate and significant (P < 0.05) reduction of ankle plantar flexor and hip adductor spasticity, with a partial increase in the range of the active and passive motion at the ankle and in gait velocity. At an individual level, six of 15 patients showed an increase in gait velocity. The FAC and RMA did not change. Patients often reported partial improvement in foot position and lower limb propulsion, and fair satisfaction. In conclusion, botulinum toxin injection can be effective in HSP patients with relatively ancient spasticity. This technique can be introduced into the therapeutic panel, which also includes physiotherapy, oral treatment and baclofen pump.

[Post stroke hemiplegia: interest of botulinum toxin injection at the upper limb]. / Hémiplégie vasculaire: intérêt de l'injection de toxine botulique au membre supérieur.

OBJECTIVES: To present data about the effect of botulinum toxin injection on the upper limb of stroke patients. METHODS: We used the Medline data bank. Analysis took into account the international classification of functioning and disability. Important technical or pragmatic points were analysed separately. RESULTS: Botulinum toxin reduces spasticity of the injected muscles, with a mean gain of about 1 point on the Ashworth scale in the 4 to 6 weeks post injection, but with a large variability. This is associated to an increase in the passive range of motion, especially at wrist, and at times to a facilitation of active movements, when they are still possible. Improvement in functional tests is observed when fair proximal and distal motricity persists. Reduction in the dependence in daily living activities has not been shown by group studies. Several patients have an improvement in using the hand for blocking and transporting objects, mainly in a facilitating position (pronation, partial wrist flexion). Comfort of patients and caregivers is more regularly improved. Results are partially predictable; improvement in function is observed in patients with fair distal motricity (extension) and low spasticity, and improvement in comfort in those with severe spasticity and low motricity. CONCLUSION: Further studies are required, on one hand for better assessment of distal functional improvement, on the other hand at earlier phases of the disease.