Real world experience of therapeutic monitoring of medically treated prosthetic valve infective endocarditis by 18F-FDG-PET/CT.

INTRODUCTION: 18F-FDG-PET/CT is recommended to improve the diagnosis of prosthetic valve infective endocarditis (PVIE) and is a major criterion in the ESC-2015 classification. However, there is little evidence for its usefulness in the follow-up of medically treated PVIE patients. METHODS: A monocentric retrospective analysis of patients hospitalized for PVIE between January 2013 and December 2019 who were not treated with surgery and who had at least two 18F-FDG-PET/CT examinations during their medical management. RESULTS: Among 170 patients with PVIE, 117 were treated with antibiotic therapy but no surgery. Of these, 36 (31%) had at least two 18F-FDG-PET/CT examinations. At initial imaging, 28 patients had heterogeneous FDG uptake on their prosthetic valve and eight on their associated aortic graft. Hypermetabolism of spleen and bone marrow (HSBM) was observed in 18 and 19 patients, respectively. At the first follow-up 18F-FDG-PET/CT, 21 (58%) patients still had heterogeneous uptake, indicating persistent active endocarditis. HSBM was still present at the last follow-up imaging in four of the six patients with recurrent PVIE. CONCLUSION: 18F-FDG-PET/CT monitoring of medically treated patients with PVIE provides valuable additional information and prospective multicentric study should be conducted to assess its usefulness.

Over-blending effect of lubricants on capsules manufacturing: a simple and fast wettability technique to predict batch dissolution performance.

Mixing/blending is a crucial operation in the manufacturing of solid drug products in the pharmaceutical industry. Although usually described and controlled in specific steps, blending is also inherent to other operations such as the transference of materials and equipment feeding systems. This study aimed to investigate a simple and fast wettability testing procedure capable to foresee the potential over-blending effects of lubricants occurring during the manufacturing of solid dosage forms. An industrial batch blend was submitted to two mixing mechanisms studies (diffusion and shear) during increasing time periods, and the developed wettability testing procedure was applied to assess their impact on blend water uptake. Capsules filled with these blends were tested for dissolution and disintegration. The method was applied to capsules with known dissolution results manufactured at an industrial scale. Results demonstrated that processes inducing shear stress led to less permeable blends with consequent retardation on capsules dissolution of at least 35% in the tested timepoints and obtained study metrics above 500 s. Moreover, disintegration testing was not able to detect non-compliant dissolutions, while the proposed wettability testing procedure proved to be able to identify performance failures. Wettability results correlate the effect of mixing mechanisms to capsules dissolution performance, evidencing that this technique can be applied in the pharmaceutical industry to evaluate possible over-blending effects.

The ScRALF3 secreted peptide is involved in sporophyte to gametophyte signalling and affects pollen mitosis I.

Signalling events through small peptides are essential in multiple aspects of plant reproduction. The ScRALF3 Solanum chacoense Rapid Alkalinization Factor (RALF) peptide was previously shown to regulate multiple aspects of cell-cell communication between the surrounding sporophytic tissue and the female gametophyte during ovule development. We analysed the global expression pattern of ScRALF3 with GUS reporter gene under control of the ScRALF3 promoter and validated it with in situ hybridisation. To better understand the role of ScRALF3 we used three different RNA interference (RNAi) lines that reduced the expression of ScRALF3 during pollen development. Both expression methods showed the presence of ScRALF3 in different tissues, including stigma, style, vascular tissues and during stamen development. Down-regulation of ScRALF3 expression through RNAi showed drastic defects in early stages of pollen development, mainly on the first mitosis. These results suggest that the ScRALF3 secreted peptide regulates the transition from sporogenesis to gametogenesis in both male and female gametophytes.

Single dose escalation studies with inhaled POL6014, a potent novel selective reversible inhibitor of human neutrophil elastase, in healthy volunteers and subjects with cystic fibrosis.

BACKGROUND: POL6014 is a novel, orally inhaled neutrophil elastase (NE) inhibitor in development for cystic fibrosis (CF). METHODS: Two studies, one in healthy volunteers (HVs, doses 20 to 960 mg) and one in subjects with CF (doses 80 to 320 mg) were conducted to evaluate the safety, tolerability and pharmacokinetics (PK) of single ascending doses of inhaled POL6014 with a Pari eFlow® nebuliser. PK was evaluated over a period of 24 h. In addition, NE activity in CF sputum was measured. RESULTS: After single doses, POL6014 was safe and well tolerated up to 480 mg in HVs and at all doses in subjects with CF. POL6014 showed a dose-linear PK profile in both populations with Cmax between 0.2 and 2.5 µM in HVs and between 0.2 and 0.5 µM in subjects with CF. Tmax was reached at approximately 2-3 h. Mean POL6014 levels in CF sputum rapidly reached 1000 µM and were still above 10 µM at 24 h. >1-log reduction of active NE was observed at 3 h after dosing. CONCLUSION: Inhalation of POL6014 can safely lead to high concentrations within the lung and simultaneously low plasma concentrations, allowing for a clear inhibition of NE in the sputum of subjects with CF after single dosing. TRIAL REGISTRATION: European Medicines Agency EudraCT-Nr. 2015-001618-83 and 2016-000493-38.

[Chyle leak after cervical surgery: Meta analysis--Management strategy]. / Lymphorrhée après chirurgie cervicale: méta-analyse--stratégie thérapeutique.

OBJECTIVE: Chyle fistula is a known complication in cervical surgery. It can lead to a postoperative lymphorrhea. There is no consensus on its management. The aim of this work is to propose a management strategy for postoperative chyle leak. MATERIALS AND METHODS: A literature review was conducted using PubMed database. RESULTS: Six prospectives articles were included. The enteral diet allowed a success in 57% of cases, and in these cases a lymph flow less than 580 mL/day. Parenteral nutrition was effective when the flow was less than 1050 mL/day. Reoperation was performed in case of failure of the nutritional treatments. CONCLUSION: Several therapeutics are available. From this meta-analysis, we developed a management strategy. We initiate an enteral diet when lymph flow is less than 500 mL/ day. Parenteral nutrition is used if the flow rate is between 500 and 1000 mL/day or in case of inefficiency of enteral diet during 10 days. Finally, revision surgery is necessary when the flow is greater than 1000 mL/day or when parenteral nutrition was ineffective in 10 days.

The novel CXCR4 antagonist POL5551 mobilizes hematopoietic stem and progenitor cells with greater efficiency than Plerixafor.

Mobilized blood has supplanted bone marrow (BM) as the primary source of hematopoietic stem cells for autologous and allogeneic stem cell transplantation. Pharmacologically enforced egress of hematopoietic stem cells from BM, or mobilization, has been achieved by directly or indirectly targeting the CXCL12/CXCR4 axis. Shortcomings of the standard mobilizing agent, granulocyte colony-stimulating factor (G-CSF), administered alone or in combination with the only approved CXCR4 antagonist, Plerixafor, continue to fuel the quest for new mobilizing agents. Using Protein Epitope Mimetics technology, a novel peptidic CXCR4 antagonist, POL5551, was developed. In vitro data presented herein indicate high affinity to and specificity for CXCR4. POL5551 exhibited rapid mobilization kinetics and unprecedented efficiency in C57BL/6 mice, exceeding that of Plerixafor and at higher doses also of G-CSF. POL5551-mobilized stem cells demonstrated adequate transplantation properties. In contrast to G-CSF, POL5551 did not induce major morphological changes in the BM of mice. Moreover, we provide evidence of direct POL5551 binding to hematopoietic stem and progenitor cells (HSPCs) in vivo, strengthening the hypothesis that CXCR4 antagonists mediate mobilization by direct targeting of HSPCs. In summary, POL5551 is a potent mobilizing agent for HSPCs in mice with promising therapeutic potential if these data can be corroborated in humans.

Lack of involvement of type 7 phosphodiesterase in an experimental model of asthma.

Type 7 phosphodiesterases (PDE7) are responsible for the decrease of intracellular cyclic AMP (cAMP) in many cells involved in allergic asthma by suppressing their potential to respond to many activating stimuli. The elevation of intracellular cAMP has been associated with immunosuppressive and anti-inflammatory activities and represents a potential treatment of asthma. Our aim was to evaluate the impact of the deletion of the murine phosphodiesterase (PDE)7B gene and then to evaluate the efficacy of a newly described selective PDE7A and -B inhibitor on an ovalbumin (OVA)-induced airway inflammation and airway hyperreactivity (AHR) model in mice. Inflammation was determined 72 h after single OVA challenge or 24 h after multiple challenges by the relative cell influx and cytokine content in bronchoalveolar lavage fluid. AHR and immunoglobulin E levels in serum were determined after multiple challenges. For the first time, we have demonstrated that the deletion of the PDE7B gene or the pharmacological inhibition of PDE7A and -B had no effect on all the parameters looked at in this model. These results highlight the absence of any implication of the PDE7 enzyme in our model.

Ibuprofen-loaded calcium phosphate granules: combination of innovative characterization methods to relate mechanical strength to drug location.

This paper studies the impact of the location of a drug substance on the physicochemical and mechanical properties of two types of calcium phosphate granules loaded with seven different contents of ibuprofen, ranging from 1.75% to 46%. These implantable agglomerates were produced by either low or high shear granulation. Unloaded Mi-Pro pellets presented higher sphericity and mechanical properties, but were slightly less porous than Kenwood granules (57.7% vs 61.2%). Nevertheless, the whole expected quantity of ibuprofen could be integrated into both types of granules. A combination of surface analysis, using near-infrared (NIR) spectroscopy coupling chemical imaging, and pellet porosity, by mercury intrusion measurements, allowed ibuprofen to be located. It was shown that, from 0% to 22% drug content, ibuprofen deposited simultaneously on the granule surface, as evidenced by the increase in surface NIR signal, and inside the pores, as highlighted by the decrease in pore volume. From 22%, porosity was almost filled, and additional drug substance coated the granule surfaces, leading to a large increase in the surface NIR signal. This coating was more regular for Mi-Pro pellets owing to their higher sphericity and greater surface deposition of drug substance. Unit crush tests using a microindenter revealed that ibuprofen loading enhanced the mechanical strength of granules, especially above 22% drug content, which was favorable to further application of the granules as a bone defect filler.

Comparison of low-shear and high-shear granulation processes: effect on implantable calcium phosphate granule properties.

BACKGROUND: Calcium phosphate porous ceramics present a great interest not only as complex bone defect fillers but also as drug delivery systems. Most of the methods described in the literature to fabricate pellets are based on compaction, casting into spherical molds, or on processes such as liquid immiscibility or foaming. Despite wet granulation is used in a wide range of applications in pharmaceuticals, food, detergents, fertilizers, and minerals, it is not applied in the biomaterial field to produce granules. METHODS: In this study physicochemical and in vitro drug delivery properties of implantable calcium phosphate granules, produced by two wet agglomeration processes, were compared. Pellets obtained by high shear granulation (granulation in a Mi-Pro apparatus) were shown to be more spherical and less friable than granules elaborated by low shear process (granulation in a Kenwood apparatus). Although Mi-Pro pellets had a slightly lower porosity compared to Kenwood granules, ibuprofen loading efficiency and dissolution profiles were not statistically different and the release mechanism was mainly controlled by diffusion, in both cases. CONCLUSION: Mi-Pro pellets appeared to be better candidates as bone defect fillers and local drug delivery systems as far as they were more spherical and less friable than Kenwood agglomerates.

A novel application of the T-cell for flow-through dissolution: the case of bioceramics used as ibuprofen carrier.

This paper describes the use of a novel flow cell, the T-cell, adapted to the flow-through cell apparatus, for the study of ibuprofen release from implantable loaded pellets and its performance in comparison to the compendial tablet cell. In fact, the drug targeting with a local delivery system becomes increasingly used to achieve therapeutic doses directly on the implantation site while maintaining a low systemic drug level. Due to the long and expensive in vivo studies necessary to evaluate the efficacy of such delivery systems, in vitro dissolution techniques are performed despite there being no standard method in the biomaterial field. In this work, dissolution profiles obtained with the T-cell configuration clearly indicate a prolonged release of ibuprofen. Dissolution data fitted to Higuchi, Hixson-Crowell, Ritger-Peppas and Kopcha equations indicate the coexistence of diffusion and erosion mechanisms governing ibuprofen release. T-cell adapted to the standard flow-through dissolution apparatus is shown to better simulate in vivo conditions than the tablet cell. This is relevant for in vivo/in vitro correlations.

Influence of process parameters on pellets elaborated in a Mi-pro high-shear granulator.

The aim of the study was to prepare porous pellets several hundred micrometers in diameter into or onto which drug substances could be embedded. Wet granulation was carried out on a powder mix of alpha-lactose and polyvinylpyrrolidone in a Mi-Pro high-shear granulator. The process parameters were investigated to point out their influence on pellet physical properties. The reference conditions of granulation that gave the most satisfactory pellets in size and shape were determined by adjusting the volume and the distribution rate of water. Increasing impeller speed resulted in an increase in granule size and granulation yield and in a decrease in proportion of fines. The granules showed easy flowing for all granulation conditions. Adjusting process parameters enabled control of size, shape, surface area, and porosity of the granules and thus the design of ready to use granules to which drug substances could be associated by deposition or inclusion.

[Assessing quality in the process of using hazardous drugs-prescription and preparation]. / Evaluación de la calidad en el proceso de utilización de fármacos peligrosos: prescripción y preparación.

OBJECTIVE: To evaluate the quality of cytotoxic drug prescription based on the results of an interventional pharmaceutical program and the quality of the final product based on quality-control prior to preparation. STUDY PERIOD: July 2002-March 2003. Hazardous drug prescription was evaluated through an analysis of pharmaceutical interventions during therapeutical monitoring. Depending on repercussion in patients, they were classified in three categories (treatment optimization, resource optimization or criteria unification). Data obtained from manual quality control programs prior to hazardous drug preparation were evaluated. RESULTS: Sixty-four interventions were made (9 interventions per 100 prescriptions): 55% were classified as treatment optimization, 28% as resource optimization and 17% as criteria unification. A total of 66% of the interventions focused on treatment optimization were caused by prescription errors. Ninety-seven per cent were accepted. Out of 2,074 preparations, 1,951 were evaluated (94.9%). A 5.1% of non-evaluated preparations were due to a lack of registration and 0.8% to violations in the established protocol. CONCLUSIONS: Results of the interventional Pharmaceutical program show that an assisted prescription system is necessary, not only to detect prescription errors but also to prevent them. Manual controls in different stages of the process are useful and they should be complementary to other more reliable dosification controls.

Evaluación de la calidad en el proceso de utilización de fármacos peligrosos: prescripción y preparación / Assesing quality in the process of using hazarous drugs-prescription and preparation

Objetivo: Evaluar la calidad de la prescripción de citostáticos a partir de los resultados obtenidos en el programa de intervenciones farmacéuticas y la calidad de la preparación mediante un control de calidad realizado de forma previa a la elaboración. Métodos: Periodo de estudio: julio 2002-marzo 2003. Prescripción: se evaluó mediante el análisis de las intervenciones farmacéuticas realizadas durante la monitorización terapéutica de los tratamientos con fármacos peligrosos. Para su evaluación se clasificaron en 3 categorías según la repercusión en el paciente (optimización del tratamiento, optimización de recursos, unificación de criterios). Preparación: se evaluaron los registros obtenidos en el programa de control de calidad manual, previo a la elaboración de las preparaciones de fármacos peligrosos. Resultados: Se realizaron 64 intervenciones (9 intervenciones por cada 100 prescripciones): 55% fueron para optimizar el tratamiento, 28% para optimizar recursos, 17% para unificar criterios. De las intervenciones enfocadas a optimizar el tratamiento, un 66% fueron por errores de prescripción. El 97% de las intervenciones fueron aceptadas. De las 2.074 preparaciones realizadas se evaluaron 1.951 (94,9%). De las preparaciones no evaluadas, un 5,1% fue por falta de registro y un 0,8% por falta de cumplimiento del protocolo establecido. Conclusiones: Los resultados obtenidos en el programa de intervenciones farmacéuticas evidencian la necesidad de implantar un sistema de prescripción asistida, que nos permitirá actuar no sólo en la detección de errores de prescripción, sino en su prevención. La realización de controles manuales en diferentes puntos del proceso de elaboración resulta útil y debería ser una medida complementaria a otros controles más fiables de dosificación

Objective: To evaluate the quality of cytotoxic drug prescription based on the results of an interventional pharmaceutical program and the quality of the final product based on quality-control prior to preparation. Methods: Study period: July 2002-March 2003. Hazardous drug prescription was evaluated through an analysis of pharmaceutical interventions during therapeutical monitoring. Depending on repercussion in patients, they were classified in three categories (treatment optimization, resource optimization or criteria unification). Data obtained from manual quality-control programs prior to hazardous drug preparation were evaluated. Results: Sixty-four interventions were made (9 interventions per 100 prescriptions): 55% were classified as treatment optimization, 28% as resource optimization and 17% as criteria unification. A total of 66% of the interventions focused on treatment optimization were caused by prescription errors. Ninety-seven per cent were accepted. Out of 2,074 preparations, 1,951 were evaluated (94.9%). A 5.1% of non-evaluated preparations were due to a lack of registration and 0.8% to violations in the established protocol. Conclusions: Results of the interventional pharmaceutical program show that an assisted prescription system is necessary, not only to detect prescription errors but also to prevent them. Manual controls in different stages of the process are useful and they should be complementary to other more reliable dosification controls

[Infections by Candida sp. in intensive care. Survey of French practices]. / Infections à Candida sp en réanimation. Enquête sur les pratiques françaises.

OBJECTIVE: The isolation of Candida sp in nosocomial infections is on the increase and over the past 10 years many guidelines for "good" practices and recommendations have been published on the modalities for the management of systemic candidiasis. The aim of this paper was to assess the habits in the intensive care units in this domain in France. METHOD: A transversal survey on the habits was conducted from March to May 2001, using a questionnaire mailed to 200 intensive care units. RESULTS: One hundred eighty questionnaires (surgical reanimation: 12%, medical: 18%, medico-surgical: 70%) out of 200 (92.5%) were returned. The indirect diagnostic examinations: serology, search for antigenemia and PCR (Polymerase Chain Reaction) were never used in 21, 35 and 65% of cases. The systematic search for colonisation (a mean of 4 areas sampled) was conducted in all the patients by 19% of the investigators, in some patients by 53%, and never by 28%. An antifungal treatment was prescribed: in the presence of a positive haemoculture alone, once out of twice if the sample had been taken from a central catheter and in 2 cases out of 3 when the sample was peripheral. It was prescribed 6 times out of 10 after isolation of Candida sp following surgery or on needle aspiration of an intra-abdominal abscess, varyingly in the case of cadiduria, isolation of a Candida sp in a broncho-pulmonary sample or in abdominal draining and positive culture of a catheter, depending on the intensity of the colonisation, the severity of the clinical picture and the presence of factors of risk for Candida infection. It is still prescribed empirically depending on the same elements and the absence of explanation for worsening. When faced with candidemia in a non-neutropenic patient, a central catheter is not changed in 18% of cases. Depending on the microbiology, fluconazole is prescribed in: the identification of yeast without further precision (78% of cases), Candida sp without further precision (86% of cases), Candida non albicans without further precision (57% of cases), C. albicans (93% of cases), Candida non albicans other than C. krusei and C. glabrata (62% of cases), C. glabrata (36% of cases) with an increase in dose in 1 out of 2 cases. In the presence of C. glabrata or C. krusei, amphotericin B is the choice in respectively 51 and 75% of cases. To adapt the treatment.

Excitatory granule cells of the dentate gyrus exhibit a double inhibitory neurochemical content after intrahippocampal administration of kainate in adult mice.

We have previously demonstrated that, in the adult mouse, injection of kainate/AMPA receptors agonists into the dorsal hippocampus induces major structural modifications of the dentate gyrus granule cells. Such changes are mediated by the brain-derived neurotrophic factor (BDNF). Considering previous involvements of BDNF in activity-linked regulations of hippocampal neuronal phenotype, changes of neurochemical contents were further investigated. It is shown that excitatory granule cells rapidly acquire a strong immunoreactivity for the inhibitory neurotransmitters GABA and neuropeptide-Y, with different patterns for both molecules. GABA immunoreactivity appeared first in mossy fibers, before extending to cell bodies and dendrites. Analysis of glutamic acid decarboxylase revealed slight increases in mossy fibers and no somatic labeling. In contrast to GABA, neuropeptide-Y labeling was observed first in granule cell soma and then in mossy fibers, with a centrifugal gradient. All labelings were transient, but slight amounts of GABA and NPY were kept in some cell bodies for at least 6 months. Confocal microscope analysis of double GABA/NPY labelings revealed colocalization of both mediators in the same neurons. The specificity of kainate-linked changes was suggested by lack of immunoreactivity for somatostatin. These results show that the capacities of mature granule cells to adapt environmental modifications can concern neurochemical contents, by synthesis and/or uptake of specific molecules. The fact that adaptive changes are rapid and transient suggests a direct response to kainate, in order to limit its potentially deleterious effects. Colocalization of GABA and neuropeptide-Y indicates that the dentate gyrus granule cells can use several pathways to this aim.

Reduction of ischemic damage in NGF-transgenic mice: correlation with enhancement of antioxidant enzyme activities.

If permanent focal ischemia is induced by middle cerebral artery occlusion (MCAO), neurons within the infarcted territory die by necrosis and apoptosis (or programmed cell death). We have previously shown, using a mouse strain transgenic (tg) for the nerve growth factor (NGF) gene, that tg mice have consistently smaller infarcted areas than wild-type (wt) animals, correlated with upregulated NGF synthesis and impaired apoptotic cell death. We studied, in wt and tg mice subjected to MCAO, the activities of several antioxidant enzymes and the synthesis of the proteins of the Bcl-2 family. Our results show that the antiapoptotic Bcl-2 protein and glutathione peroxidase are recruited after MCAO. NGF-tg mice also had an intrinsic resistance to oxidative stress because their basal copper zinc superoxide dismutase (SOD) and glutathione transferase activities were high. Additionally, manganese SOD activity increased in NGF-tg mice after MCAO, correlating strongly with the resistance of these mice to apoptosis.

Detection of known and new mutations in the thiopurine S-methyltransferase gene by single-strand conformation polymorphism analysis.

To detect mutations in the thiopurine S-methyltransferase gene (TPMT), we have developed a strategy based on single-strand conformation polymorphism (SSCP) analysis of the gene amplified by polymerase chain reaction (PCR). The sensitivity of the method was first evaluated by analyzing DNA samples from five individuals, including two high methylators (HMs), two intermediate methylators (IMs), and one deficient methylator (DM). TPMT alleles and mutations in each of these individuals had previously been characterized by conventional PCR-based assays and direct sequencing analysis. All mutations were associated with particular shifts in the electrophoretic mobility of DNA fragments, allowing their identification. We further tested the efficiency of the strategy to detect new TPMT mutations. For this purpose, additional DNAs from 15 IMs and 15 HMs were submitted to PCR-SSCP analysis. A total of 7 alleles were characterized, including two new alleles. The first one, termed TPMT*1A, harbors a single mutation C-->T at nucleotide -178 in exon 1 and was detected in a HM subject. The second one, termed TPMT*7, was characterized by a T-->G transversion at nucleotide 681 in exon 10. This allele should be a nonfunctional allele of the TPMT gene since it was observed in combination with a wild-type allele in an intermediate methylator. We conclude that the PCR-SSCP strategy we developed could be advantageously used to fully characterize the extent of allelic variation at the TPMT gene locus in populations and thus to improve our understanding of the genetic polymorphism of TPMT activity, which has considerable consequences for the toxicity and efficacy of therapeutically important and widely used drugs.

[Atelectasis of the maxillary sinus. Analysis of progression stages. Apropos of 4 cases]. / Processus atélectasique du sinus maxillaire. Analyse des stades évolutifs. A propos de 4 cas.

We analyzed atelectasic processes occurring in the maxillary sinus. Several publications in the literature have tempted to analyze the pathogenesis. Clinically the processes are often silent and only revealed when the major opthalmological complication, enophthalmia, becomes patent. In other cases there is a long history of chronic sinusitis. There is a spectacular retraction of the maxillary sinus walls leading to collapse of the orbital floor and enophthalmia. We report four cases of maxillary sinusitis with atelectasia of the sinus walls at different stages of progression. These observations and data in the literature emphasize the importance, whatever the state of development, of endoscopic osteal decompression to avoid ophthalmological complications.

[Atypical involvement of undifferentiated carcinomas of the nasopharyngeal type. Apropos of 3 cases]. / Localisations atypiques des carcinomes indifférenciés de type nasopharyngé. A propos de 3 cas.

We report 3 cases of undifferentiated carcinomas of nasopharyngeal type (UCNT) found in unusual sites and compare them with histologically identical tumors found in the nasopharynx. Using viral serology and viral marquers found in the tumor cells, we looked for a link with the Epstein Barr Virus (EBV) which exists in the nasopharyngeal site. It appears that UCNT found in unusual sites have a poorer prognostic than the same nasopharyngeal tumors; no link was found with EBV. The number of published cases is too small to form a conclusion, therefore, we propose a systematic search for EBV, presenting our protocol, each time is discovered UCNT in an unusual site.

[Use of endoscopy in pituitary surgery]. / Utilisation de l'endoscopie dans la chirurgie pituitaire.

Endoscopy has changed many of surgical procedures concerning nasal and paranasal cavities. It has been proposed for transnasal removal of pituitary adenomas. The authors report their experience concerning four pituitary macroadenomas operated with the neurosurgical team of Sainte-Anne hospital. The endonasal trans-septal route seemed to be more anatomical and less traumatic than the rhinoseptal sublabial route. The 30 degrees rigid Hopkins endoscope was a good help for controlling the absence of any tumor remnant in the supra and parasellar regions after complete removal of the tumor performed through the endoscope or with the operating microscope. The authors discuss the advantages and limitations of such endoscopic procedures in the light of recent literature.