[General practitioners' knowledge on means of prescribing speech therapy]. / Connaissances des médecins généralistes sur les modalités de prescription de l'orthophonie.

INTRODUCTION: General practitioners are the first prescribers of speech therapy in France, a country in which speech therapists can practice only on medical prescription. The objective of this study was to measure general practioner's knowledge on means of prescribing speech therapy. METHOD: Cross-sectional study by self-questionnaires for general practitioners and residents in general practice in France. The test assessed five types of knowledge conducive to correct prescription of speech therapy: requirements for prescription, indications, prescription wording, ages of treatment eligibility, and reimbursement. The questionnaires were tested on an expert population, whose median score was used as a cut-off to separate doctors who knew the modalities of speech therapy prescription from those whose knowledge was insufficient. The characteristics differentiating the two groups were compared by multiple logistic regression. RESULTS: Five hundred and three general practitioners and five hundred and two residents in general medicine were included; 82.3% of the physicians having written a thesis and 86.2% of the residents had insufficient knowledge of the modalities of speech therapy prescription. Age, number of years since acquisition of a medical diploma and urban practice all had a negative impact on general practitioners' knowledge of speech therapy. CONCLUSION: French general practitioners' knowledge of speech therapy prescription seems insufficient. It is consequently necessary to improve the initial and continuing training of doctors. Collaborative work between general practitioners and speech therapists should be carried on, developed and strengthened.

GALV expression enhances the therapeutic efficacy of an oncolytic adenovirus by inducing cell fusion and enhancing virus distribution.

The limitations of the current oncolytic adenoviruses for cancer therapy include insufficient potency and poor distribution of the virus throughout the tumor mass. To address these problems, we generated an oncolytic adenovirus expressing the hyperfusogenic form of the gibbon-ape leukemia virus (GALV) envelope glycoprotein under the control of the adenovirus major late promoter. The oncolytic properties of the new fusogenic adenovirus, ICOVIR16, were analyzed both in vitro and in vivo, and compared with that of its non-fusogenic counterpart, ICOVIR15. Our results indicate that GALV expression by ICOVIR16 induced extensive syncytia formation and enhanced tumor cell killing in a variety of tumor cell types. When injected intratumorally or intravenously into mice with large pre-established melanoma or pancreatic tumors, ICOVIR16 rapidly reduced tumor burden, and in some cases, resulted in complete eradication of the tumors. Importantly, GALV expression induced tumor cell fusion in vivo and enhanced the spreading of the virus throughout the tumor. Taken together, these results indicate that GALV expression can improve the antitumoral potency of an oncolytic adenovirus and suggest that ICOVIR16 is a promising candidate for clinical evaluation in patients with cancer.

The course of primary progressive aphasia diagnosis: a cross-sectional study.

BACKGROUND: The primary progressive aphasia (PPA) diagnosis trajectory is debated, as several changes in diagnosis occur during PPA course, due to phenotype evolution from isolated language alterations to global cognitive impairment. The goal of the present study, based on a French cohort, was to describe the demographics and the evolution of subjects with (PPA) in comparison with Alzheimer's disease (AD) on a period of 7 years. METHODS: We conducted a repeated cross-sectional study. The study population comprised individuals with PPA and AD diagnosis (N=167,191) from 2010 to 2016 in the French National data Bank (BNA). Demographic variables, MMSE scores, diagnosis status at each visit and prescribed treatments were considered. RESULTS: From 2010 to 2016, 5186 patients were initially diagnosed with PPA, 162,005 with AD. Compared to AD subjects, significant differences were found concerning age (younger at first diagnosis for PPA), gender (more balanced in PPA), education level (higher in PPA) and MMSE score (higher of 1 point in PPA). Percentage of pending diagnosis, delay between first consultation and first diagnosis and the number of different diagnoses before the diagnosis of interest were significantly higher in PPA group compared to AD group. Pharmacological and non-pharmacological treatments were significatively more recommended following PPA than AD diagnosis. CONCLUSION: This study improves the knowledge of PPA epidemiology and has the potential to help adopting appropriate public health service policies. It supports the hypothesis that PPA is diagnosed later than AD. The PPA diagnosis increases the prescription of non-pharmacological treatments, especially speech and language therapy (SLT) that is the main treatment available and most effective when at the initial stage. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT03687112.

How Dominant Hand and Foot Dexterity May Reveal Dementia Onset: A Motor and Cognitive Dual-Task Study.

The combined provision of an arising number of dementia cases, and the substantial absence of effective treatments, led the scientific community toward the identification of early phases of this condition. Such an effort aims at the recognition of therapeutic windows and the characterization of the disease's different grades. In the last years, Motor and Cognitive Dual-Tasks (MCDT) have been widely used to address the early diagnosis of several neurocognitive disorders, among which dementia. Here we present different protocols: the walking MCDT, the toe-tapping MCDT, and the forefinger-tapping MCDT. Moreover, each task has been performed under different cognitive conditions: no cognitive effort, counting backwards by 1, 3, and 7. In this work, we report the results obtained through the combination of different motor and cognitive tasks, and we present 2 brand-new MCDT protocols, attempting to identify a sweet-spot for early diagnosis of dementia.

A modified E2F-1 promoter improves the efficacy to toxicity ratio of oncolytic adenoviruses.

The E2F-1 promoter has been used to confer tumor-selective E1A expression in oncolytic adenoviruses. Tumor specificity is mainly conferred by a unique structure of E2F-responsive sites organized in palindromes. Binding of the E2F-pRb complex to these palindromes results in repression of transcription in normal cells. Owing to deregulation of the Rb/p16 pathway in tumor cells, binding of free E2F activates transcription and initiates an autoactivation loop involving E1A and E4-6/7. ICOVIR-7 is a new oncolytic adenovirus designed to increase the E2F dependency of E1A gene expression. It incorporates additional palindromes of E2F-responsive sites in an insulated E2F-1 promoter controlling E1A-Delta24. The E2F palindromes inhibited replication in normal cells, resulting in a low systemic toxicity at high doses in immunocompetent mice. The Delta24 deletion avoids a loop of E2F-mediated self-activation in nontumor cells. Importantly, the additional E2F-binding hairpins boost the positive feedback loop on the basis of E1A-mediated transcriptional regulation of E4-6/7 turned on in cancer cells and increased antitumoral potency as shown in murine subcutaneous xenograft models treated by intravenous injection. These results suggest that the unique genetic combination featured in ICOVIR-7 may be promising for treating disseminated neoplasias.

Electrical impedance tomography compared to positron emission tomography for the measurement of regional lung ventilation: an experimental study.

INTRODUCTION: Electrical impedance tomography (EIT), which can assess regional lung ventilation at the bedside, has never been compared with positron-emission tomography (PET), a gold-standard to quantify regional ventilation. This experiment systematically compared both techniques in injured and non-injured lungs. METHODS: The study was performed in six mechanically ventilated female piglets. In normal lungs, tidal volume (VT) was randomly changed to 6, 8, 10 and 15 ml/kg on zero end-expiratory pressure (ZEEP), then, at VT 10 ml/kg, positive end-expiratory pressure (PEEP) was randomly changed to 5, 10 and 15 cmH2O. Afterwards, acute lung injury (ALI) was subsequently created in three animals by injecting 3 ml/kg hydrochloric acid into the trachea. Then at PEEP 5 cmH2O, VT was randomly changed to 8 and 12 ml/kg and PEEP of 10 and 15 cmH2O applied at VT 10 ml/kg. EIT and PET examinations were performed simultaneously. EIT ventilation (VTEIT) and lung volume (VL) were measured in the anterior and posterior area of each lung. On the same regions of interest, ventilation (VPET) and aerated lung volume (VAatten) were determined with PET. RESULTS: On ZEEP, VTEIT and VPET significantly correlated for global (VTEIT = VPET - 2E-13, R2 = 0.95, P < 0.001) and regional (VTEIT = 0.81VPET+7.65, R2 = 0.63, P < 0.001) ventilation over both conditions. For ALI condition, corresponding R2 were 0.91 and 0.73 (P < 0.01). Bias was = 0 and limits of agreement were -37.42 and +37.42 ml/min for global ventilation over both conditions. These values were 0.04 and -29.01 and +29.08 ml/min, respectively, for regional ventilation. Significant correlations were also found between VL and VAatten for global (VL = VAatten+1E-12, R2 = 0.93, P < 0.0001) and regional (VL = 0.99VAatten+0.92, R2 = 0.65, P < 0.001) volume. For ALI condition, corresponding R2 were 0.94 (P < 0.001) and 0.54 (P < 0.05). Bias was = 0 and limits of agreement ranged -38.16 and +38.16 ml for global ventilation over both conditions. These values were -0.24 and -31.96 to +31.48 ml, respectively, for regional ventilation. CONCLUSIONS: Regional lung ventilation and volume were accurately measured with EIT in healthy and injured lungs and validated by simultaneous PET imaging.

Feasibility and safety of ultra-low tidal volume ventilation without extracorporeal circulation in moderately severe and severe ARDS patients.

PURPOSE: Mechanical ventilation with ultra-low tidal volume (VT) during ARDS may reduce alveolar strain, driving pressure and hence ventilator-induced lung injury, with the main drawback of worsening respiratory acidosis. We hypothesized that VT could be reduced down to 4 ml/kg, with clinically significant decrease in driving pressure, without the need for extracorporeal CO2 removal, while maintaining pH > 7.20. METHODS: We conducted a non-experimental before-and-after multicenter study on 35 ARDS patients with PaO2/FiO2 ≤ 150 mmHg, within 24 h of ARDS diagnosis. After inclusion, VT was reduced to 4 ml/kg and further adjusted to maintain pH ≥ 7.20, respiratory rate was increased up to 40 min-1 and PEEP was set using a PEEP-FiO2 table. The primary judgment criterion was driving pressure on day 2 of the study, as compared to inclusion. RESULTS: From inclusion to day 2, driving pressure decreased significantly from 12 [9-15]  to 8 [6-11] cmH2O, while VT decreased from 6.0 [5.9-6.1] to 4.1 [4.0-4.7] ml/kg. On day 2, VT was below 4.2 ml/kg in 65% [CI95% 48%-79%], and below 5.25 ml/kg in 88% [CI95% 74%-95%] of the patients. 2 patients (6%) developed acute cor pulmonale after inclusion. Eleven patients (32%) developed transient severe acidosis with pH < 7.15. Fourteen patients (41%) died before day 90. CONCLUSION: Ultra-low tidal volume ventilation may be applied in approximately 2/3 of moderately severe-to-severe ARDS patients, with a 4 cmH2O median reduction in driving pressure, at the price of transient episodes of severe acidosis in approximately 1/3 of the patients.

Syncytia formation affects the yield and cytotoxicity of an adenovirus expressing a fusogenic glycoprotein at a late stage of replication.

Fusogenic membrane glycoproteins (FMGs) may enhance the cytotoxicity of conditionally replicative adenoviruses. However, expression at early stages of infection impairs virus replication. We have inserted the hyperfusogenic form of the gibbon ape leukemia virus (GALV) envelope glycoprotein as a new splice unit of the major late promoter (MLP) to generate a replication-competent adenovirus expressing this protein. At high multiplicity of infection (MOI), this virus replicated efficiently forming clumps of fused cells and showing a faster release. In contrast, at low MOI, infected cells formed syncytia where only one nucleus contained virus DNA, decreasing total virus production but increasing cytotoxicity.

Evaluation of rotation thrombelastography for the diagnosis of hyperfibrinolysis in trauma patients.

BACKGROUND: Blood loss and uncontrollable bleeding are major factors affecting survival in trauma patients. Because treatment with antifibrinolytic drugs may be effective, early detection of hyperfibrinolysis with rotation thrombelastography (ROTEM may be beneficial. METHODS: Eighty-seven trauma patients were included in this prospective observational study. Blood samples were collected at admission. After in vitro activation with tissue factor (EXTEM) and inhibition with aprotinin (APTEM), ROTEM parameters including maximal clot firmness (MCF) and clot lysis index at 30 min (CLI(30)) were determined. Hyperfibrinolysis was defined as a euglobulin lysis time (ELT) <90 min. Threshold for ROTEM parameters were determined with receiver-operating characteristic curves (ROC) analysis according to the ELT results. RESULTS: ELT was determined in a subgroup of 23 patients. In this group of patients, ROC analysis showed that for a threshold of 18 mm (MCF-EXTEM), 71% (CLI(30)) and 7% (increase of MCF-APTEM), sensitivity was, respectively, 100%, 75%, and 80% with a specificity of 100%. With the application of these thresholds to the whole trauma cohort, ROTEM analysis detected hyperfibrinolysis in five patients [6%, 95% confidence interval (CI): 2-13%]. As expected, patients with hyperfibrinolysis were more severely injured (median Injury Severity Score: 75 vs 20, P<0.05), had greater coagulation abnormalities [international normalized ratio (INR): 8.2 vs 1.3, P<0.05; fibrinogen: 0.0 vs 2.2 g litre(-1), P<0.05], and a higher mortality rate (100%, CI: 48-100% vs 11% CI: 5-20%, P<0.05). CONCLUSIONS: ROTEM provided rapid and accurate detection of hyperfibrinolysis in severely injured trauma patients.

Sex ratio in dementia with Lewy bodies balanced between Alzheimer's disease and Parkinson's disease dementia: a cross-sectional study.

BACKGROUND: Gender distribution varies across neurodegenerative disorders, with, traditionally, a higher female frequency reported in Alzheimer's disease (AD) and a higher male frequency in Parkinson's disease (PD). Conflicting results on gender distribution are reported concerning dementia with Lewy bodies (DLB), usually considered as an intermediate disease between AD and PD. The aim of the present study was to investigate gender differences in DLB in French specialized memory settings using data from the French national database spanning from 2010 to 2015 and to compare sex ratio in DLB with that in AD, Parkinson's disease dementia (PDD), and PD. Our hypothesis was that there is a balanced sex ratio in DLB, different from that found in AD and PD. METHODS: We conducted a repeated cross-sectional study. The study population comprised individuals with a DLB, AD, PDD, or PD diagnosis according to the International Classification of Diseases, Tenth Revision, in the French National Alzheimer Database between 2010 and 2015. Sex ratio and demographic data were compared using multinomial logistic regression and a Bayesian statistical model. RESULTS: From 2010 to 2015 in French specialized memory settings, sex ratios (female percent/male percent) were found as follows: 1.21 (54.7%/45.3%) for DLB (n = 10,309), 2.34 (70.1%/29.9%) for AD (n = 135,664), 0.76 (43.1%/56.9%) for PD (n = 8744), and 0.83 (45.4%/54.6%) for PDD (n = 3198). Significant differences were found between each group, but not between PDD and PD, which had a similar sex ratio. CONCLUSIONS: This large-sample prevalence study confirms the balanced gender distribution in the DLB population compared with AD and PD-PDD. Gender distribution and general demographic characteristics differed between DLB and PDD. This is consistent with the hypothesis that DLB is a distinct disease with characteristics intermediate between AD and PD, as well as with the hypothesis that DLB could have at least partially distinct neuropathological correlates.

Diagnosis of early coagulation abnormalities in trauma patients by rotation thrombelastography.

BACKGROUND: Reagent-supported thromboelastometry with the rotation thrombelastography (e.g. ROTEM) is a whole blood assay that evaluates the visco-elastic properties during blood clot formation and clot lysis. A hemostatic monitor capable of rapid and accurate detection of clinical coagulopathy within the resuscitation room could improve management of bleeding after trauma. OBJECTIVES: The goals of this study were to establish whether ROTEM correlated with standard coagulation parameters to rapidly detect bleeding disorders and whether it can help to guide transfusion. METHODS: Ninety trauma patients were included in the study. At admission, standard coagulation assays were performed and ROTEM parameters such as clot formation time (CFT) and clot amplitude (CA) were obtained at 15 min (CA(15)) with two activated tests (INTEM, EXTEM) and at 10 min (CA(10)) with a test analyzing specifically the fibrin component of coagulation (FIBTEM). RESULTS: Trauma induced significant modifications of coagulation as assessed by standard assays and ROTEM. A significant correlation was found between prothrombin time (PT) and CA(15)-EXTEM (r = 0.66, P < 0.0001), between activated partial thromboplastin time and CFT-INTEM (r = 0.91, P < 0.0001), between fibrinogen level and CA(10)-FIBTEM (r = 0.85, P < 0.0001), and between platelet count and CA(15)-INTEM (r = 0.57, P < 0.0001). A cutoff value of CA(15)-EXTEM at 32 mm and CA(10)-FIBTEM at 5 mm presented a good sensitivity (87% and 91%) and specificity (100% and 85%) to detect a PT > 1.5 of control value and a fibrinogen less than 1 g L(-1), respectively. CONCLUSIONS: ROTEM is a point-of-care device that rapidly detects systemic changes of in vivo coagulation in trauma patients, and it might be a helpful device in guiding transfusion.

Olfactory disturbances in ageing with and without dementia: towards new diagnostic tools.

BACKGROUND: Olfactory disorders increase with age and often affect elderly people who have pre-dementia or dementia. Despite the frequent occurrence of olfactory changes at the early stages of neurodegenerative disorders such as Alzheimer's disease, olfactory disorders are rarely assessed in daily clinical practice, mainly due to a lack of standardised assessment tools. The aims of this review were to (1) summarise the existing literature on olfactory disorders in ageing populations and patients with neurodegenerative disorders; (2) present the strengths and weaknesses of current olfactory disorder assessment tools; and (3) discuss the benefits of developing specific olfactory tests for neurodegenerative diseases. METHODS: A systematic review was performed of literature published between 2000 and 2015 addressing olfactory disorders in elderly people with or without Alzheimer's disease or other related disorders to identify the main tools currently used for olfactory disorder assessment. RESULTS: Olfactory disorder assessment is a promising method for improving both the early and differential diagnosis of Alzheimer's disease. However, the current lack of consensus on which tests should be used does not permit the consistent integration of olfactory disorder assessment into clinical settings. CONCLUSION: Otolaryngologists are encouraged to use olfactory tests in older adults to help predict the development of neurodegenerative diseases. Olfactory tests should be specifically adapted to assess olfactory disorders in Alzheimer's disease patients.

Feasibility studies of large scale production of human anti-tetanus toxoid monoclonal antibodies.

The feasibility of large scale production of human anti-tetanus toxoid monoclonal antibody for therapeutic use was evaluated using a human heterohybridoma. The effects of duration of subculture, transition from static to agitated culture conditions and the level of serum concentration were studied. The level of antibody secreted by the clone decreased with increasing length of subculture and decreasing serum concentration. The clone exhibited heterogeneity in expression of surface IgG after 2 or 7 weeks of subculture in static culture conditions irrespective of the serum concentration. However, a prolonged duration of subculture (9 weeks) in 3% serum medium had an effect on the expression of surface IgG both in static and agitated culture conditions. With respect to total (surface and intracellular) IgG, two distinct cell populations were observed. On long term subculture (9 weeks) in low serum medium (3% FCS), there was a decrease in the population which was the high synthesizer. In addition, when these cells were cultivated in agitated spinner flasks, a defect in secretion of antibodies was observed. Thus a general fall in the amount of antibody in the supernatant of agitated cultures was due to decrease in antibody synthesis as well as the defect in secretion of antibodies.

Otoacoustic emissions and auditory assessment in infants at risk for early brain damage.

The importance of early hearing screening has long been recognized, as the prognosis for the hearing impaired child is improved when the diagnosis is made as early as possible, and the intervention is begun immediately. For clinical screening of hearing impairment, the recording of otoacoustic emissions was recommended. As some risk factors for early brain damage are at the same time also risk factors for dysfunction of auditory system, we presumed that infants at risk for brain damage have hearing impairment more frequently than the rest of the population of the same age. We were interested in the role of otoacoustic emission testing during the assessment of auditory function in these infants. There were 110 infants at risk for brain damage included in the study. After thorough otorhinolaryngological examination, auditory function was estimated by recording of otoacoustic emissions, tympanometry, pure tone audiometry and, when necessary, auditory brainstem responses. Otoacoustic emissions were recorded by Madsen-Electronics Celesta 503 in an acoustically treated sound room. We registered spontaneous as well as transient and distortion product otoacoustic emissions. The neurologist formed two groups with different degrees of neurological risk. The collected results of auditory function were compared with the degree of neurological risk. For the statistical analysis, the procedure chi(2) and Fischer test were used. Spontaneous otoacoustic emission was detected in 38.2% of examinees. Evoked otoacoustic emissions were registered in 87.3% of infants. The testing had to be repeated in 32.7% of infants. We observed evoked otoacoustic emissions to be present also in a child with sensorineural hearing impairment and no auditory brainstem responses. Up to 32.7% of infants at risk for brain damage were hard of hearing. Conductive hearing loss was discovered with 25.4% of infants, and eight (7.3%) had sensorineural hearing impairment. In the group of examinees with only risk factors 3.6% had sensorineural impairment and in a group with abnormal motor development, there were 18.5% with that kind of hearing loss. Fischer test confirmed a statistically significant difference between the groups. Infants at risk for brain damage have more frequently impaired auditory function than their peers. For this reason, it is especially important to focus attention on the hearing condition when dealing with this population. Recording of evoked otoacoustic emissions is very helpful in pediatric audiometry, but any interpretation of the results should consider the possibility of auditory neuropathy.

Does it make sense to preserve the stapedial muscle during surgical treatment for otosclerosis?

Our study aimed to show whether it is useful to preserve the stapedial muscle during the surgical treatment of otosclerosis. The study was carried out on 67 patients with tympanoscopic evidence of otosclerosis. In group A (34 patients) the stapedial muscle was intra-operatively preserved as follows: the stapedial suprastructure with preserved muscle tendon was transpositioned onto the longer arm of the incus and secured with a wire loop. The mean uncomfortable level for sounds was measured after surgery and the results of group A patients were compared with those obtained in group B (33 patients, who underwent standard surgery). One month after surgery, in group A patients, the cochleostapedial reflex was evoked in 21 patients (61.8 per cent) and two months later in 32 patients (94.1 per cent). One month after operation, in group A patients the mean uncomfortable level was 108.8 dB, while three months later it increased to 114.1 dB. In group B, the relevant values were 97.8 dB one month after surgery, and 98.0 dB three months later. Our presumption that stapedial muscle preservation is necessary has been proved by the fact that the patients with the preserved muscle had a higher noise discomfort threshold.

In vitro cultivation of third stage larvae of Wuchereria bancrofti to fourth stage: influence of some physico-chemical factors.

It has been reported that third stage larvae (L3) of Wuchereria bancrofti strain from Jakarta, molted to the fourth stage (L4) in vitro, in a simple culture medium supplemented with 10% human serum. In the present study, this culture medium has been used to examine the effects of some physico-chemical parameters on larval growth, development and molting of Wuchereria bancrofti from India. Lymph at 10% concentration enhanced the in vitro survival time of larvae. Molting of larvae from L3 to L4 stage has been obtained using human fetal lung cells in cellular co-culture and as a source of conditioned medium. Given these improvements in the medium supplementation, it has been observed that the age of L3s (duration of L3s maintenance within the mosquitos) is one of the most important parameters for the development of L3s in vitro. No molting was observed when one day L3s were used whereas, molting occurred with one or two weeks old L3s. On the contrary, when more than 3 weeks old L3s were used molting failed to occur even though duration of survival of L3s was improved and in this case, most of the larvae were degenerated.

The antitumor drug F14512 enhances cisplatin and ionizing radiation effects in head and neck squamous carcinoma cell lines.

BACKGROUND: Head and Neck Squamous Cell Carcinoma (HNSCC) is the sixth most common cancer worldwide. The treatment of advanced stages HNSCC is based on surgical treatment combined with radiotherapy and chemotherapy or concomitant chemo-radiotherapy. However, the 5-year survival remains poor for advanced stages HNSCC and the development of new targeted therapies is eagerly awaited. F14512 combines an epipodophyllotoxin core-targeting topoisomerase II with a spermine moiety introduced as a cell delivery vector. This spermine moiety facilitates selective uptake by tumor cells via the Polyamine Transport System (PTS) and reinforces topoisomerase II poisoning. Here we report the evaluation of F14512 toward HNSCC. MATERIALS AND METHODS: Four cell lines representative of head and neck cancer localizations were used: Fadu (pharynx), SQ20B (larynx), CAL33 and CAL27 (base of the tongue). PTS activity and specificity were evaluated by confocal microscopy and flow cytometry using the fluorescent probe F17073 which contains the same spermine moiety as F14512. Cytotoxicity, alone or in association with standard chemotherapeutic agents (cisplatin, 5FU), and radio-sensitizing effects were investigated using MTS and clonogenic assays, respectively. F14512 efficiency and PTS activity were also measured under hypoxic conditions (1% O2). RESULTS: In all 4 tested HNSCC lines, an active PTS was evidenced providing a specific and rapid transfer of spermine-coupled compounds into cell nuclei. Interestingly, F14512 presents a 1.6-11-fold higher cytotoxic effect than the reference compound etoposide (lacking the spermine chain). It appears also more cytotoxic than 5FU and cisplatin in all cell lines. Competition experiments with spermine confirmed the essential role of the PTS in the cell uptake and cytotoxicity of F14512. Hypoxia had almost no impact on the drug cytotoxicity. The combination of F14512 with cisplatin, but not 5FU, was found to be synergistic and, for the first time, we demonstrated the significant radio-sensitizing potential of F14512. CONCLUSION: The spermine moiety of F14512 confers a targeted effect and a much better efficacy than etoposide in HNSCC lines. The synergistic effect observed in association with cisplatin and radiotherapy augurs well for the potential development of F14512 in HNSCC.

[Acute respiratory distress syndrome related to intra-alveolar hemorrhage revealing a vasculitis]. / Syndrome de détresse respiratoire aiguë sur hémorragie intra-alvéolaire révélant une vascularite.

Intra-alveolar hemorrhage (IAH) could be revealed by acute respiratory failure. The classic association of hemoptysis - anemia - radiological infiltrates is suggestive and has to be confirmed by broncho-alveolar lavage with Golde score. Etiologies included immune and non-immune diseases, with specific treatment for each. We report a case of IAH revealed by acute respiratory distress syndrome and anemia (3 g/dL), related to pulmonary and cerebral vasculitis without renal involvement. The patient was efficiently treated with corticosteroids and cyclophosphamide. This case highlights the critical role of BAL cytological analysis with Golde score, and the need for a rapid and accurate diagnosis in order to guide specific treatment. If histology is needed, renal biopsy even without renal involvement, or surgical lung biopsy is possible.