[Renal cell carcinoma in the department of Hérault: Results over a 30 year period]. / Le cancer du rein dans le département de L'Hérault : résultats de 30 ans d'enregistrement.

OBJECTIVE: The objective of the study was to determine the specificities of renal cell carcinoma (RCC) in the department of Herault using the Herault Tumor Registry over 30 years. METHODS: Data of this study were obtained from the Herault cancer database. We analysed the evolution of RCC from 1987 to 2016, including the incidence, mortality, cancer pathology and staging at the moment of diagnosis. We compared our results with national and international data. RESULTS: We identified 3769 newly diagnosed RCC: 2628 in men (69,7%) and 1141 in women (30,3%). In 2016, RCC was the 8th most frequent cancer, both genders combined, the 7th most frequent cancer in men and the 11th in women. New cases of RCC increased by 4.2 in men and 3.3 in women over the study period. The number of localised forms increased by 9% over 20 years. In 2016, the probability of having a RCC before the age of 75 was of 2.11% for a man and of 0.62% for a woman. CONCLUSION: Over 30 years, the incidence rate of RCC increased in the department of Herault; however, mortality decreased over the same period. This analytical data should be improved by the development of the Registry of Herault Specialised in Onco-Urology (RHESOU). LEVEL OF EVIDENCE: 3.

Origen intraorbitario de las arterias etmoidales: estudio anatómico / Intraorbital origin of the ethmoidal arteries: anatomical study

RESUMEN Introducción: Ramas de la arteria oftálmica contribuyen a la irrigación de diversos territorios de la fosa nasal y de los senos paranasales. Objetivo: El objetivo de nuestro estudio es describir las arterias etmoidales desde su origen intraorbitario, y su relación con las estructuras musculares y nerviosas. Material y Método: Se realizó un estudio anatómico endoscópico en 20 fosas nasales y órbitas de diez cadáveres. Resultados: La disección del plano muscular permitió definir dos espacios de entrada a la órbita. Un primer espacio entre el músculo recto inferior y músculo recto medial (área 1) y otro entre el músculo recto medial y músculo oblicuo superior (área 2). En el área 1, la arteria oftálmica discurrió superior al nervio óptico en el 90%. La arteria etmoidal anterior se observó en todos los casos inferior al músculo oblicuo superior. En el área 2, la arteria etmoidal posterior, se localizó en todos los casos superior al músculo oblicuo superior. No se identificó la arteria etmoidal media en ningún caso. El origen de la arteria supraorbitaria se identificó entre las dos arterias etmoidales. Conclusión: La comprensión anatómica del origen intraorbitario de la arteria oftálmica permite el abordaje de determinada patología intraorbitaria compleja a través de la pared medial de la órbita.

ABSTRACT Introduction: Branches of the ophthalmic artery contribute to the irrigation of various territories of the nasal cavity and paranasal sinuses. Aim: The aim of our study is to describe the intraorbital course of the ethmoidal arteries and their relationship with the muscular and nervous structures. Material and method: We performed twenty nasal cavities and orbital dissections in ten adults cadaveric heads. Results: The dissection of the muscular orbital wall allowed defining two surgical orbital corridors, between the inferior rectus and the medial rectus muscles (area 1) and between the medial rectus and the superior oblique muscles (area 2). In area 1, the ophthalmic artery crosses over the optic nerve in 90% of the cases. The anterior ethmoidal artery was observed inferior to the superior oblique muscle. In area 2, the posterior ethmoidal artery was located superior to the superior oblique muscle in all cavities. No middle ethmoidal artery was identified. The origin of the supraorbital artery was found between the two ethmoidal arteries. Conclusions: The anatomical understanding of the intraorbital origin of the arteries of the ophthalmic artery allows perform two surgical approaches through the media orbital wall.

Sospecha clínica y tratamiento quirúrgico de los mucoceles esfenoidales / Diagnosis and surgical treatment of sphenoid mucoceles

Introducción: Los mucoceles son formaciones benignas de lento crecimiento que pueden aparecer en cualquier seno paranasal, representando el seno esfenoidal menos del 10%. Objetivo: Presentamos nuestra experiencia de mucoceles en el seno esfenoidal. Material y método: Se obtuvieron los datos a partir de nuestra base de datos que recoge prospectivamente los casos de tumores de cabeza y cuello. Entre enero 1989 y enero 2013 se registraron 58 mucoceles en 54 pacientes, de los cuales 4 (7%) eran de seno esfenoidal. Tres pacientes eran mujeres y uno varón, con edades comprendidas entre 42 y 61 años. Todas las lesiones fueron estudiadas con endoscopia nasal, tomo-grafía computarizada y resonancia magnética. Resultados: Tres pacientes presentaron un antecedente quirúrgico de seno paranasal. El síntoma más frecuente fue la cefalea (3 pacientes de 4). Dos pacientes presentaron diplopia y uno pérdida progresiva de agudeza visual, requiriendo manejo quirúrgico urgente. Todos fueron tratados con esfenoidotomía por abordaje endoscópico endonasal. Fueron dados de alta a las 48 h posteriores con antibioticoterapia. Ninguno presentó recidiva. Conclusión: Los mucoceles esfenoidales representan menos del 10% de los mucoceles nasosinusales. La pérdida de agudeza visual requiere un rápido diagnóstico y manejo terapéutico quirúrgico urgente. El tratamiento de elección es la marsupialización.

Introduction: Sinus mucoceles are benign cysts that may appear in any sinus, but only 1%-10% occur in the sphenoid sinus. Aim: We describe the cases of sphenoid sinus mucoceles seen at our centre over the last 25 years. Material and method: In a prospective review of all mucoceles diagnosed between 1989 and 2013, we identified 58 mucocels in 54 patients. Four of the 58 (7%) were sphenoid mucoceles. There were three female patients and one male, and ages ranged from 42 to 61 years. We performed an endoscopy, CT and MR in all patients to confirm diagnosis. Results: Three patients had had endoscopic endonasal surgery in the past. The presenting symptoms were headache in 3 patients, diplopia in two, and visual loss, causing blindness, in one. The patient with amaurosis requiered urgent surgery. All four patients underwent sphenoidotomy with marsupialisation by the endonasal endoscopic approach. They were discharged 48 hours later on oral antibiotics. No recurrences have been observed to date. Conclusions: Sphenoid mucocele is a rare disease, requiring prompt treatment in cases of amaurosis. Good results can be achieved with endonasal endoscopic marsupialisation.

Semaphorin 7A inhibits platelet production from CD34+ progenitor cells.

BACKGROUND: The multifunctional protein semaphorin 7A (Sema7A) may have regulatory effects on blood cell differentiation via its receptors ß1-integrin and plexin C1. As thrombocytopenia can be treated with transfusion of ex vivo CD34(+) cell-derived megakaryocytes, we investigated the effect of Sema7A on differentiation of CD34(+) progenitor cells into megakaryocytes and platelets. METHODS: Megakaryocytes and platelets were differentiated with a specific cytokine cocktail (CC) from CD34(+) progenitor cells in the presence or absence of Sema7A. Expression of cell markers CD41, CD42a and CD61 or detection of the activation of the signal mediator focal adhesion kinase (FAK) was performed by flow cytometry, cytokine secretion by Luminex technology, and megakaryocyte cell density and morphology by microscopic studies. Sema7A levels in vivo were assessed by real-time PCR and ELISA in hematological patients undergoing chemotherapy. RESULTS: CD34(+) progenitor cells expressed the receptors for Sema7A. Expression of CD41, CD42a and CD61 was markedly reduced in the presence of Sema7A, after CC-dependent platelet production from CD34(+) progenitor cells. As revealed by microscopic analysis, megakaryocyte cell density was significantly lower in the presence of Sema7A as compared with controls. Blocking of CD29 abrogated the Sema7A-mediated inhibition. Sema7A activated FAK in CD34(+) progenitor cells and significantly increased secretion of the proinflammatory cytokines IL-6, IL-8 and GM-CSF. Finally, Sema7A levels were up-regulated in 50% of patients after chemotherapy. CONCLUSIONS: Sema7A markedly reduces the production rates of megakaryocytes and platelets from CD34(+) progenitor cells. Hence, up-regulation of Sema7A may be a major risk factor for a reduced platelet repopulation after hematopoietic stem cell transplantation.

Plasmacytoid dendritic cells reduce HIV production in elite controllers.

HIV elite controllers (EC) are a rare group of HIV-infected patients who are able to maintain undetectable viral loads during a long period of time in the absence of antiretroviral treatment. Adaptive immunity and host genetic factors, although implicated, do not entirely explain this phenomenon. On the other hand, plasmacytoid dendritic cells (pDCs) are the principal type I interferon (IFN) producers in response to viral infection, and it is unknown whether pDCs are involved in the control of HIV infection in EC. In our study, we analyzed peripheral pDC levels and IFN-α production by peripheral blood mononuclear cells (PBMCs) in EC compared to other groups of HIV-infected patients, the ability of pDCs to reduce HIV production in vitro, and the mechanisms potentially involved. We showed preserved pDC counts and IFN-α production in EC. We also observed a higher capacity of pDCs from EC to reduce HIV production and to induce T cell apoptosis, whereas pDCs from viremic patients barely responded without previous Toll-like receptor 9 (TLR-9) stimulus. The preserved functionality of pDCs from EC to reduce viral production may be one of the mechanisms involved in the control of HIV viremia in these subjects. These results demonstrate the importance of innate immunity in HIV pathogenesis, and an understanding of pDC mechanisms would be helpful for the design of new therapies.

The novel allele HLA-B*35:167 differs from HLA-B*35:03:01 by the amino acid exchange Val152Glu.

HLA-B*35:167 allele differs from HLA-B*35:03:01 and HLA-B*35:70 by an amino acid exchange at position 152.

[Adenovirus infections in children: experience in the field of the allogeneic stem cell transplantation]. / Les infections à adénovirus chez l'enfant: expérience dans le domaine de l'allogreffe de cellules souches hématopoïétiques.

UNLABELLED: Adenovirus (Adv) infections are frequent in pediatric patients, sometimes serious, above all in immunocompromised children. We report the cases of 2 children who presented an Adv infection after allogeneic stem cell transplantation (SCT). CASE REPORTS: Case n(o) 1 concerns a boy who received SCT at the age of 6 years. He had a hemorragic cystitis, which resolved after antiviral treatment and successful engraftment. Case n(o) 2 concerns a boy who received SCT at the age of 2. He shortly presented a disseminated infection, and died in spite of antiviral treatment and re-infusion of an autologous transplant. DISCUSSION: T-cell depletion (mainly carried out in vivo at present) is the major risk factor of Adv infection after allogeneic SCT. It is important to be recognized, in order to proceed to a routine screening among transplanted patients. Moreover, the detection of viral genoma by molecular biology is a predictive factor of disseminated disease development, with mortality rates higher than 50%. Early treatment is thus crucial. Immunotherapy is to be developed, by tapering of immunosuppression, or by manipulating grafts and donor lymphocyte infusions, in order to improve Adv specific responses. The possibility of a prophylaxis is still to be investigated.

Localization of VGLUT3, the vesicular glutamate transporter type 3, in the rat brain.

We have recently identified a third subtype of glutamate vesicular transporter (VGLUT) named VGLUT3. In the present study, we provide a detailed account of the regional and cellular distributions of VGLUT3 in the rat brain, using specific nucleotide probes and antisera. The distribution of VGLUT3 protein was compared with that of the other vesicular transporters (VGLUT1 and VGLUT2). All the areas expressing VGLUT3 also contain high levels of VGLUT1 and -2 proteins, but, at a finer level of analysis, the distribution of the three subtypes differs. Unlike VGLUT1 and -2, VGLUT3 expression is limited to discrete cell populations. Neurons containing VGLUT3 transcript are essentially observed in the caudate-putamen, the olfactory tubercle, the nucleus accumbens, the hippocampus, the interpeduncular nucleus and the dorsal and medial raphe nuclei. More scattered populations of VGLUT3 expressing neurons are found in the cerebral cortex. The distribution of the VGLUT3 protein, as determined with specific antisera, overlaps with that of the transcript in the caudate-putamen, olfactory tubercles, hippocampus, cortex, interpeduncular nucleus, and raphe nuclei, suggesting that VGLUT3 is essentially present in local projection neurons in these regions. Microscopic examination reveals staining of terminals and perikarya. Furthermore, co-localization studies indicate that VGLUT3 is present in GABAergic interneurons in the hippocampus, as well as in the interpeduncular nucleus. However, other regions, such as the substantia nigra (pars compacta), the ventral tegmental area, and the parabigeminal nucleus, receive a dense VGLUT3 terminal labeling although they do not contain VGLUT3 expressing neurons. In these regions, VGLUT3 immunoreactivity may be present in terminals of long projecting neurons. This subclass of glutamatergic afferents differs from other "classical" excitatory terminals that express VGLUT1 or VGLUT2. The distribution of VGLUT3 in the rat brain suggests an unsuspected function of vesicular glutamate transport in subsets of interneurons and in neuromodulatory neurons.

The existence of a second vesicular glutamate transporter specifies subpopulations of glutamatergic neurons.

Before their exocytotic release during stimulation of nerve terminals, nonpeptide neurotransmitters are loaded into synaptic vesicles by specific transporters. Recently, a protein initially identified as brain-specific Na(+)-dependent inorganic phosphate transporter I (BNPI) has been shown to represent a vesicular glutamate transporter (VGLUT1). In this study, we investigated whether a highly homologous "differentiation-associated Na(+)-dependent inorganic phosphate transporter" (DNPI) is involved in glutamatergic transmission. Vesicles isolated from BON cells expressing recombinant DNPI accumulated l-glutamate with bioenergetical and pharmacological characteristics identical to those displayed by VGLUT1 and by brain synaptic vesicles. Moreover, DNPI localized to synaptic vesicles, at synapses exhibiting classical excitatory features. DNPI thus represents a novel vesicular glutamate transporter (VGLUT2). The distributions of each VGLUT transcript in brain were highly complementary, with only a partial regional and cellular overlap. At the protein level, we could only detect either VGLUT1- or VGLUT2-expressing presynaptic boutons. The existence of two VGLUTs thus defines distinct subsets of glutamatergic neurons.

[Bilateral monitoring of cerebral oxygen saturation in aortic arch surgery]. / Bilaterales Monitoring der zerebralen Sauerstoffsättigung in der Aortenbogen-Chirurgie.

Cerebral ischemia with consecutive neurological damage is a typical complication in aortic arch surgery. Therefore, intraoperative neuromonitoring is of increasing interest. This paper describes the role of bilateral near-infrared-spectroscopy (NIRS) in detecting cerebral ischemia. In the case of a patient with acute aortic dissection (Daily, type A), an unexpected sudden reduction of perfusion of the right carotid artery could easily be detected with the help of two instruments INVOS 3100A. The decrease in the saturation values from 74% to 54% correlated well with the drop of blood pressure in the right radial artery. Clamping of the aorta with interruption of the blood flow into the innominate artery through the false lumen was the reason for the low cerebral perfusion. After repositioning the aortic clamp NIRS in combination with invasive blood pressure monitoring sufficiently allowed to control the further course of cerebral perfusion. The NIRS is a non-invasive, easy to handle, and easy to interpret method for intraoperative monitoring of the neurological status. Therefore in our opinion it has got some relevant advantages in contrast to other neuromonitoring methods in aortic arch surgery.

[Imported dengue hemorrhagic fever: aprops of 1 case presenting with signs of acute alithiasic cholecystitis]. / Dengue hémorragique d'importation: à propos d'un cas ayant présenté des signes de cholécystite aiguë alithiasique.

Dengue is prevalent in all subtropical areas. Hemorrhagic forms of the disease were first described in southeast Asia but have now been observed on several continents. Travelers are at risk for infection and the likelihood of imported dengue has grown in relation to volume of air traffic. In developed countries, dengue usually presents in the benign form, but sudden aggravation is always possible. The purpose of this report is to describe a case of imported dengue hemorrhagic fever associated with abdominal pain in a traveler returning from Asia. Radiological findings were suggestive of nonlithiasic cholecystitis. Similar ultrasound feature have been reported by pediatric groups during dengue outbreaks in Asia. Previous findings have shown that bladder involvement is a predictive sign of severe disease and impending shock. Surgery is contraindicated in these patients. Close clinical and laboratory surveillance is necessary due to the high risk of aggravation. The pathogenesis of this severe life-threatening form of the disease is unclear. A possible explanation is involvement of a more virulent strain of virus. Dengue should always be considered after malaria in the differential diagnosis of returning travelers patients presenting fever.

The comparative efficacy and tolerability of CGP 56697 (artemether + lumefantrine) versus halofantrine in the treatment of uncomplicated falciparum malaria in travellers returning from the Tropics to The Netherlands and France.

CGP 56697 (Riamet) is a new oral anti-malarial drug composed of artemether and lumefantrine (benflumetol) which combines the fast, short-acting artemether for rapid parasite clearance with the prolonged action of lumefantrine for intended radical cure. In this double-blind, comparative trial, the efficacy and tolerability of CGP 56697, given as a course of 4 x 4 tablets over 48 h, was compared to halofantrine, given as 3 x 2 tablets over 12 h with a second course 1 week later. Patients (mostly non-immune) with acute, uncomplicated Plasmodium falciparum infection were randomly assigned to either CGP 56697 (n = 51) or halofantrine (n = 52). CGP 56697 proved superior with respect to parasite clearance time (median 32 vs. 48 h, P < 0.001) and parasite reduction at 24 h (median 99.7 vs. 89.6%, P < 0.001) with a non-significant difference in resolution of fever (median 24 vs. 32 h, P = 0.835). However, a 28-day cure rate of 82% was observed for CGP 56697 and 100% for halofantrine. Significant QTc prolongations (> 30 ms) were seen 6-12 h after halofantrine intake but not after CGP 56697 intake. CGP 56697 is an effective, well-tolerated treatment for uncomplicated falciparum malaria but for this dosing regimen the recrudescence rate is unacceptablyhigh (18%). For travellers contracting malaria abroad, we propose a six-dose regimen of CGP 56697 over 3 days.

[Diagnostic and treatment of hypereosinophilia upon return from the tropics: 102 patients]. / Diagnostic et traitement des hypereosinophilies sanguines au retour des tropiques: a propos de 102 patients.

Management of blood eosinophilia in travelers returning from the tropics is controversial. In this prospective study, 102 asymptomatic tropical travelers underwent investigation and treatment for hypereosinophilia. In contrast with direct tests for parasitic infection which were positive in only 15% of cases, immunological tests were suggestive of helminthic infection is 77%. The most common diagnoses were toxocarosis (49%), strongyloidiasis (30%), and filariasis (19%). Anti-parasite treatment was undertaken based on laboratory findings (12 cases) or on presumptive diagnosis using two-agent therapy (ivermectin and praziquantel) in 13 cases or three-agent therapy (ivermectin, praziquantel, flubendazole) in 77 cases. As a result of treatment, eosinophil count returned to normal in 61% of cases and decreased in 30%. These findings suggest that presumptive treatment of blood eosinophilia can be undertaken in tropical travelers using three anti-parasitic drugs: ivermectin (1 x 0.4 mg/kg), flubendazole (2 x 100 mg per day for 3 days), and praziquantel (1 x 40 mg). As a precaution before using ivermectin, tests should be performed to detect loiasis which can lead to adverse reactions.