Original Article
Nasal Gel and Olfactory Cleft
Gel nasal y hendidura olfatoria
Jesús Herranz González-Botas
, Anselmo Padín Seara
Corresponding author
Servicio de Otorrinolaringología, Complejo Hospitalario Universitario A Coruña, A Coruña, Spain
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(B) Radial design of the applicator head.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">The functions of the nasal cavity are filtering, warming and humidifying inspired air in order to protect the airway. Particles which become trapped in the nasal mucus are transported through the action of the cilia in the nasal epithelium towards the nasopharynx and the digestive system. The anatomical design of the nasal fossa facilitates the contact of air with the nasal mucosa and conditions airflow through it. The use of specific intranasal medication for local processes is useful as long as it reaches key areas such as the ostiomeatal complex or the Eustachian tube. Therefore, knowledge of its distribution is important, both to assess its effects and to evaluate possible side effects on sensitive areas, such as the olfactory epithelium.</p><p id="par0010" class="elsevierStylePara elsevierViewall">Intranasal administration of medication is often used in sinus conditions, a problem affecting approximately 1 000 000 people per year in Spain,<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> and nearly 40 000 000 in the U.S.A.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> Its safety has been confirmed in multiple studies<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,3</span></a> and its advantages over the oral route include rapid bioavailability in the bloodstream, preventing degradation in the gastrointestinal tract and prior passage through the liver. Its disadvantages include poor contact with the nasal mucosa and difficulty to reach specific areas, critical to its therapeutic effect.<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2–7</span></a> There are multiple types of administration systems<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6,8</span></a> and head positions for better distribution,<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6,9</span></a> so there have been numerous key recommendations based on literature reviews.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> However, studies have shown that, using the usual methods, the distribution of intranasally applied medication is localised mainly in the anterior portion of the nasal cavity.</p><p id="par0015" class="elsevierStylePara elsevierViewall">Anosmia has been reported as a side effect of intranasal medication, secondary to zinc content. A possible cause would be the contact of medication with the epithelium of the olfactory region,<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> but the possibility of distributing a nasal gel at the level of the olfactory area is highly implausible.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">The aim of this study is to assess whether a viscous gel, administered through a nasal inhaler with a radial head, can reach the olfactory cleft, and whether its nasal distribution varies depending on the delivery system employed.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Material and Method</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Study Population</span><p id="par0025" class="elsevierStylePara elsevierViewall">The study was conducted among healthy volunteers who had been previously informed of its conditions and characteristics. As a prerequisite, they had to sign a consent form which included the study characteristics, the material used and its possible side effects. We studied a total of 16 volunteers whose medical histories were assessed in order to rule out nasal condition or use of medication that could affect study results. They all underwent nasal endoscopy in order to confirm the absence of septal or septopyramidal deformity, as well as to assess the visibility of the olfactory area according to the following grades: 0, not visible; 1, partially visible; 2, visible after introducing the endoscope 2<span class="elsevierStyleHsp" style=""></span>cm; and 3, easily visible. The visualisation characteristics of the olfactory cleft are shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0030" class="elsevierStylePara elsevierViewall">The mean age of patients was 25<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>3 years (maximum: 28; minimum: 22), distributed equally between men and women. None of them had a previous history of nasal or systemic disease or of use of topical or systemic medication in the previous month. The inclusion criteria are summarised in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>.</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Study Period</span><p id="par0035" class="elsevierStylePara elsevierViewall">The study was conducted in January 2012.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Statistical Analysis</span><p id="par0040" class="elsevierStylePara elsevierViewall">We conducted statistical analysis using Fisher's test, with a confidence interval of 95% (<span class="elsevierStyleItalic">α</span>=0.05).</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Method</span><p id="par0045" class="elsevierStylePara elsevierViewall">After assessing the visibility of their olfactory cleft, patients were given indications for nasal gel application, following different instructions for each nostril. In the right nostril, they had to place the applicator vertically, introducing its upper end into the nostril and breathing deeply at the time of gel application. In the left nostril, they had to place the applicator in a horizontal position, directing the upper end towards the outer edge of the left eye and without breathing deeply at the time of gel application.</p><p id="par0050" class="elsevierStylePara elsevierViewall">Nasal endoscopies were performed 1<span class="elsevierStyleHsp" style=""></span>min and 7<span class="elsevierStyleHsp" style=""></span>min after applying the gel, in order to detect presence of dye in the following anatomical structures:<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">-</span><p id="par0055" class="elsevierStylePara elsevierViewall">Nasal vestibule.</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">-</span><p id="par0060" class="elsevierStylePara elsevierViewall">Septum.</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">-</span><p id="par0065" class="elsevierStylePara elsevierViewall">Inferior turbinate.</p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">-</span><p id="par0070" class="elsevierStylePara elsevierViewall">Middle turbinate.</p></li><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">-</span><p id="par0075" class="elsevierStylePara elsevierViewall">Inferior meatus.</p></li><li class="elsevierStyleListItem" id="lsti0030"><span class="elsevierStyleLabel">-</span><p id="par0080" class="elsevierStylePara elsevierViewall">Middle meatus.</p></li><li class="elsevierStyleListItem" id="lsti0035"><span class="elsevierStyleLabel">-</span><p id="par0085" class="elsevierStylePara elsevierViewall">Olfactory cleft.</p></li></ul></p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Material</span><p id="par0090" class="elsevierStylePara elsevierViewall">The radial head applicator used in this study was a medication spray which administered 140<span class="elsevierStyleHsp" style=""></span>μl per dose (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>), manufactured by Aptar Pharma SAP #10277363. The liquid gel was produced by Unicep Packaging (Sandpoint, Idaho). It had no active ingredient and instead contained methylene blue (used as a dye), benzalkonium chloride, glycerine, hydroxyethyl cellulose, purified water and sodium chloride. The final viscosity of the product was 5500<span class="elsevierStyleHsp" style=""></span>cps. Gel ingredients and their percentages are shown in <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia></span></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Results</span><p id="par0095" class="elsevierStylePara elsevierViewall">We did not find stained gel at the level of the olfactory cleft, middle meatus or middle turbinate in any of the volunteers tested, on either side, in the endoscopy conducted at 1<span class="elsevierStyleHsp" style=""></span>min or at 7<span class="elsevierStyleHsp" style=""></span>min.</p><p id="par0100" class="elsevierStylePara elsevierViewall">In all cases we found stained gel at the level of the nasal vestibule, in both nostrils and during both endoscopies.</p><p id="par0105" class="elsevierStylePara elsevierViewall">On the right side, the inferior turbinate was the second location in frequency, with a percentage of dye of 87% at 1<span class="elsevierStyleHsp" style=""></span>min and 75% at 7<span class="elsevierStyleHsp" style=""></span>min. It was followed in frequency by the septum, with 75% and 62% at 1<span class="elsevierStyleHsp" style=""></span>min and 7<span class="elsevierStyleHsp" style=""></span>min, respectively, and by the inferior meatus, with 6.2% and 12.5% at 1<span class="elsevierStyleHsp" style=""></span>min and 7<span class="elsevierStyleHsp" style=""></span>min, respectively.</p><p id="par0110" class="elsevierStylePara elsevierViewall">The distribution of dye on the left side was more discreet. The second area in frequency was the nasal septum, with 18.7% and 13.5% at 1<span class="elsevierStyleHsp" style=""></span>min and 7<span class="elsevierStyleHsp" style=""></span>min, respectively, followed by the inferior meatus, which presented 6.5% in both endoscopies. Dye was not located in the inferior turbinate on this side.</p><p id="par0115" class="elsevierStylePara elsevierViewall">The Fisher test showed significant differences in the distribution of gel at the level of the septum (<span class="elsevierStyleItalic">P</span><.01) and inferior turbinate (<span class="elsevierStyleItalic">P</span><.001), when comparing both methods of application (<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>).</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Discussion</span><p id="par0120" class="elsevierStylePara elsevierViewall">The result of our study shows that a viscous gel administered through a nasal applicator with radial head was not able to reach the upper portion of the nasal fossa, as no dye was found in the olfactory cleft, middle turbinate and middle meatus. The modification of the application method did not result in better distribution at the top of the nasal fossa and only showed differences in distribution at the levels of the septum and inferior turbinate. Previous studies have shown that the distribution of medication administered intranasally is mainly located in the anterior nasal fossa (septum, vestibule and inferior turbinate) regardless of the application method employed.<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2,7,11</span></a> The nasal valve area is the narrowest part of the nasal fossa, separating the vestibule from the fossa itself. This structure is located about 2<span class="elsevierStyleHsp" style=""></span>cm from the edge of the nostril and has a midsection of about 0.7<span class="elsevierStyleHsp" style=""></span>cm. The greatest resistance to airflow takes place at the inferior turbinate head level. All these anatomical characteristics justify the difficulties for the passage and distribution of gel to deeper and superior areas of the nasal fossa.</p><p id="par0125" class="elsevierStylePara elsevierViewall">This study was performed on healthy individuals without previous nasal condition or nasal obstruction and with a visible olfactory area, so additional obstructive factors were ruled out. We did not use topical anaesthesia or pledgets soaked in vasoconstrictor so as not to alter the characteristics of the nasal mucosa, avoiding the appearance of rhinorrhea and sneezing which would introduce a bias in the distribution of gel.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a></p><p id="par0130" class="elsevierStylePara elsevierViewall">The stained gel was found in all cases in the nasal vestibule, an area lined with multilayered squamous epithelium, unable to transport and mobilise secretions. Therefore, the gel remained at that location until it disappeared or was eliminated by the patient.</p><p id="par0135" class="elsevierStylePara elsevierViewall">Ciliated epithelium, located after the nasal valve, is capable of transporting nasal mucus and any substances trapped in it to the nasopharynx. The mean nasal mucus clearance time in healthy individuals is 30<span class="elsevierStyleHsp" style=""></span>min,<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> although this period may vary depending on the anatomical characteristics of each individual, local disease, mucus characteristics and use of medication.<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">13,14</span></a> No significant differences were found in nasal mucus clearance time when comparing a saline nasal spray and a gel spray, both stained with fluorescein.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a></p><p id="par0140" class="elsevierStylePara elsevierViewall">Due to its high viscosity, the nasal gel offered a lower tendency to drip, as well as reducing unpleasant taste sensations related to swallowing of the product.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> Since the direction of transport by ciliated epithelium is towards the nasopharynx and due to the effect of gravity, we can assume that transport of the gel towards the top of the nose after 7<span class="elsevierStyleHsp" style=""></span>min is very unlikely.</p><p id="par0145" class="elsevierStylePara elsevierViewall">The modifications made on applicators and solutions have shown best results with sprays in which the pressure is obtained by manual pumping rather than pressurised sprays,<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> but no improvement in distribution was obtained when comparing nasal sprays and drops.<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8,16,17</span></a> A previous study, which used a single-orifice applicator, showed similar results, with examinations performed up to 15<span class="elsevierStyleHsp" style=""></span>min after gel application,<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> with no changes in explorations conducted in 45 patients. Therefore, we decided not to perform endoscopies after 7<span class="elsevierStyleHsp" style=""></span>min, since this procedure causes discomfort for patients and increases rhinorrhea, a factor that could affect the results of the study.</p><p id="par0150" class="elsevierStylePara elsevierViewall">Modifications were designed to enable passage of the nasal valve and thus increase distribution in critical areas, mainly at the level of the nasal infundibulum, a key area in sinonasal conditions.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a></p><p id="par0155" class="elsevierStylePara elsevierViewall">Scheibe et al. studied different methods to reach the olfactory area. They considered that, since systemic corticosteroids were effective in the treatment of sudden anosmia, topical corticosteroids could also be useful, and concluded that the reason was due to their inability to reach the olfactory area.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> They reached the olfactory area in 73% of cases in which dyed saline solution was injected into the nostril using a syringe with a needle. This percentage dropped to 6.6% when the serum was applied with a spray and to 0% when it was administered as drops. A vasoconstrictor was used in all subjects 15<span class="elsevierStyleHsp" style=""></span>min before application of the serum and 3 consecutive doses were used.</p><p id="par0160" class="elsevierStylePara elsevierViewall">The position of the head also affects intranasal distribution because airflow and gravity hinder the arrival of medication to the top of the nose, a critical area in sinonasal condition.<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2,8,9,19</span></a> Cannady et al. found that, in patients who had previously undergone endoscopic sinus surgery, with 3 drops of fluorescein-dyed dexamethasone applied to a patient in the nasal vestibule with the head vertex placed toward the ground (a position known as “praying to Mecca”), the deposit at the olfactory area level was higher if the position was maintained for 5<span class="elsevierStyleHsp" style=""></span>min than if it was maintained for only 1<span class="elsevierStyleHsp" style=""></span>min.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> They found no differences between applying the product and maintaining the head vertex toward the ground for 1<span class="elsevierStyleHsp" style=""></span>min, and application of the product through a syringe inserted into the nostril between 3 and 5<span class="elsevierStyleHsp" style=""></span>mm and directed towards the external edge of the ipsilateral eye.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> Merkus et al. found no differences in distribution at the level of the middle meatus when comparing 4 different head positions (upright, hyperextended, on one side and with the vertex toward the ground) and 3 different applicator models.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> They concluded that the position with the vertex towards the ground enabled greater product distribution at the top of the nasal fossa, and that this could improve the delivery of medication to the olfactory area in patients with nasal polyposis.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a></p><p id="par0165" class="elsevierStylePara elsevierViewall">Taking a deep breath while administering the product was not associated with better distribution in the nasal fossa.<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2,19</span></a> We found a better distribution in the head of the inferior turbinate, but did not identify the presence of gel at the level of the middle turbinate, middle meatus and olfactory cleft.</p><p id="par0170" class="elsevierStylePara elsevierViewall">Guo et al. analysed intranasal distribution in terms of different viscosities with the product applied and found no differences when combining different methods of application. They concluded that different methods of application do not alter distribution because airflow has little influence on product distribution and deposition.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> Particles leaving the applicator head impact on the vestibule and head of the inferior turbinate, without the ability to change direction and adapt to the airflow present in the area of the turbinate.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a></p><p id="par0175" class="elsevierStylePara elsevierViewall">Multiple methods have been used for the study of intranasal distribution of medication (isotopes, dyes, endoscopy, collection of product on pledgets), each with different advantages and disadvantages.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> This variability makes comparisons between studies more difficult.</p><p id="par0180" class="elsevierStylePara elsevierViewall">Intranasal endoscopic identification of dyes has been used in multiple studies.<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7,19,21</span></a> It is assumed that if the dye is identified at the level of the head of the middle turbinate, then it is possible to obtain distribution in that area, which is critical in sinonasal involvement.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> The sample size employed in most studies, as well as the methodology, was similar to that used in our study, with the difference that we specifically aimed to identify the dye at the level of the olfactory cleft, did not employ vasoconstrictor or anaesthesia, and the olfactory area was visible in all subjects.</p><p id="par0185" class="elsevierStylePara elsevierViewall">Intersubject variability was minimised because even though subjects administered the product themselves, they were controlled directly by an observer, so as to ensure that they followed the correct procedure. There are no studies which analyse inter- and intrasubject variability, and which can provide information on the effect of incorrect product application due to not following instructions.</p><p id="par0190" class="elsevierStylePara elsevierViewall">There have been reports of anosmia secondary to intranasal use of products containing zinc.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> Also, olfactory epithelium necrosis has been found in human nasal tissue cultures and in mice exposed to the product.<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> Lim et al. mentioned the difficulty of depositing nasal gel in the olfactory area of a non-anaesthetised guinea pig as an argument to criticise the methodology of the study by Slotnick et al.<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> In their study, Slotnick et al. found no relationship between a gel containing zinc and anosmia.<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a></p><p id="par0195" class="elsevierStylePara elsevierViewall">Regardless of the effect that zinc may cause on the olfactory epithelium, contact of zinc with the olfactory mucosa is necessary to generate damage in the olfactory epithelium. Therefore, the hypothesis is unlikely, taking into account that in our study we found no presence of dye in the olfactory area or in its vicinity. In clinical cases associated with the description of anosmia syndrome related to zinc, patients clearly reported burning sensation and olfactory impairment immediately or hours after administration of nasal gel while taking a deep breath. In our study, both with deep inspiration and without it, with the applicator in a vertical or horizontal position, gel distribution was localised in the anterior portion of the nose. This distribution did not change in the exploration conducted after 7<span class="elsevierStyleHsp" style=""></span>min.</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Conclusions</span><p id="par0200" class="elsevierStylePara elsevierViewall">Our study supports the concept that a viscous nasal gel is distributed in the anterior and inferior parts of the nasal fossa, primarily at the levels of the vestibule, septum and inferior turbinate, and that this distribution is not affected by the position of the applicator or by taking a deep breath at the time of application. We did not identify the presence of dyed gel in the middle turbinate, middle meatus and olfactory cleft, neither after 1<span class="elsevierStyleHsp" style=""></span>min nor after 7<span class="elsevierStyleHsp" style=""></span>min of product application. Moreover, this finding was not affected by different methods of product application. Therefore, we consider that the contact of a nasal gel with the olfactory epithelium of the olfactory cleft is highly unlikely.</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Financing</span><p id="par0205" class="elsevierStylePara elsevierViewall">This work was requested and funded by the company <span class="elsevierStyleGrantSponsor">Matrixx Initiatives, Inc.</span>, 8515 East Anderson Drive Scottsdale, AZ 85255, U.S.A.</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Conflict of interests</span><p id="par0210" class="elsevierStylePara elsevierViewall">The authors have no conflict of interests to declare.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:12 [ 0 => array:2 [ "identificador" => "xres95040" "titulo" => array:5 [ 0 => "Abstract" 1 => "Objective" 2 => "Material and method" 3 => "Results" 4 => "Conclusions" ] ] 1 => array:2 [ "identificador" => "xpalclavsec82193" "titulo" => "Keywords" ] 2 => array:2 [ "identificador" => "xres95041" "titulo" => array:5 [ 0 => "Resumen" 1 => "Objetivo" 2 => "Material y método" 3 => "Resultados" 4 => "Conclusiones" ] ] 3 => array:2 [ "identificador" => "xpalclavsec82192" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Material and Method" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Study Population" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Study Period" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Statistical Analysis" ] 3 => array:2 [ "identificador" => "sec0030" "titulo" => "Method" ] 4 => array:2 [ "identificador" => "sec0035" "titulo" => "Material" ] ] ] 6 => array:2 [ "identificador" => "sec0040" "titulo" => "Results" ] 7 => array:2 [ "identificador" => "sec0045" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0050" "titulo" => "Conclusions" ] 9 => array:2 [ "identificador" => "sec0055" "titulo" => "Financing" ] 10 => array:2 [ "identificador" => "sec0060" "titulo" => "Conflict of interests" ] 11 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2012-03-06" "fechaAceptado" => "2012-05-03" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec82193" "palabras" => array:3 [ 0 => "Intranasal preparations" 1 => "Distribution" 2 => "Olfactory cleft" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec82192" "palabras" => array:3 [ 0 => "Preparaciones intranasales" 1 => "Distribución" 2 => "Hendidura olfatoria" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<span class="elsevierStyleSectionTitle">Objective</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">To evaluate whether a nasal gel, administered using a radial-hole inhaler, reaches the olfactory cleft, and if a different administration method influences distribution.</p> <span class="elsevierStyleSectionTitle">Material and method</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Sixteen healthy volunteers underwent a nasal endoscopy at 1 and 7<span class="elsevierStyleHsp" style=""></span>min after the administration of a intranasal gel, with a different method in each fossa.</p> <span class="elsevierStyleSectionTitle">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">No dye deposition was identified at the olfactory cleft, middle turbinate or middle meatus. In all cases the gel was identified at the nasal vestibule. On the right side, the second most frequent dye identification area was the inferior turbinate, with a rate of 87% at the first minute and 75% at 7<span class="elsevierStyleHsp" style=""></span>min. It was followed by the septum (75% and 62%) and the inferior meatus (6.2% and 12.5%). On the left side, the second most frequent stained area was the septum (18.7% and 13.5%), followed by the inferior meatus (6.5% and 65%). No inferior turbinate staining was found in the left side. There was a significant difference in the deposition rate at the septum (<span class="elsevierStyleItalic">P</span><.01) and inferior turbinate (<span class="elsevierStyleItalic">P</span><.001), when both administration methods were compared.</p> <span class="elsevierStyleSectionTitle">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">No nasal gel, administered using a radial-hole inhaler, was found at the olfactory cleft, middle turbinate or middle meatus. Gel distribution was located at the anterior and inferior portion of the nose, independent of the administration method used. Significantly different gel distribution rates were found at the septum and inferior turbinate when the 2 administration methods were compared.</p>" ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "<span class="elsevierStyleSectionTitle">Objetivo</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Identificar si un gel administrado mediante un inhalador de cabeza radial puede alcanzar la hendidura olfatoria y si su distribución intranasal se modifica según el método de aplicación.</p> <span class="elsevierStyleSectionTitle">Material y método</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Se estudiaron 16 voluntarios a los que se administró un gel teñido de modo diferente en cada fosa, realizándose una endoscopia tras 1 y 7<span class="elsevierStyleHsp" style=""></span>min.</p> <span class="elsevierStyleSectionTitle">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">No se identificó gel a nivel de la hendidura olfatoria, cornete medio o meato medio independientemente del método de administración utilizado. En el vestíbulo se identificó colorante en todos los casos. En el lado derecho la segunda localización más frecuente fue el cornete inferior con una incidencia del 87% al minuto y del 75% a los 7<span class="elsevierStyleHsp" style=""></span>min. Le siguieron el tabique, 75 y 62%, y el meato inferior, 6,2 y 12,5%. En el lado izquierdo la segunda localización más frecuente fue el tabique, 18,7 y 13,5%, seguida del meato inferior, 6,5 y 65%. Las diferencias en la presencia de colorante a nivel del septo (p<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0,01) y el cornete inferior fueron significativas.</p> <span class="elsevierStyleSectionTitle">Conclusiones</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">No se ha identificado la presencia de gel a nivel de la hendidura olfatoria, cornete medio o meato medio. La distribución se localiza a nivel de la parte anterior e inferior de la fosa nasal, con diferencias significativas si se emplean métodos de administración diferentes.</p>" ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara">Please cite this article as Herranz González-Botas J, Padín Seara A. Gel nasal y hendidura olfatoria. Acta Otorrinolaringol Esp. 2012;63:370–5.</p>" ] ] "multimedia" => array:5 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1596 "Ancho" => 496 "Tamanyo" => 105424 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">(A) Nasal applicator. (B) Radial design of the applicator head.</p>" ] ] 1 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="2" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Right Side</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="2" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Left Side</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">No. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">No. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">% \t\t\t\t\t\t\n \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Grade 0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Grade 1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12.5 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Grade 2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">25 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Grade 3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">94 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">62.5 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab179908.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Visual Assessment of the Olfactory Area.</p>" ] ] 2 => array:7 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No use of medication by nasal route in the past month \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No use of medication by general route in the past month \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Absence of acute or chronic systemic involvement \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Absence of acute or chronic nasal involvement \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No history of sinonasal surgery \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Visualisation of the nasal area of grade 1 or higher \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Absence of septal or pyramidal deformity \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Informed consent \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab179907.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Inclusion Criteria for Volunteers in the Study.</p>" ] ] 3 => array:7 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Ingredient \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Percentage, % \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Function \t\t\t\t\t\t\n \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Hydroxyethyl cellulose \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Viscosity \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Glycerine \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Stability \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Sodium chloride \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Isotonic buffer \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Benzalkonium chloride \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.02 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Preservative \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Methylene blue \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.01 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Dye \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Purified water \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">∼97 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Vehicle \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab179909.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Ingredients and their Percentages in the Gel.</p>" ] ] 4 => array:7 [ "identificador" => "tbl0020" "etiqueta" => "Table 4" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">No., number of cases with positive dye identification; NS, not significant.</p><p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">Values with significant differences are shown in bold (<span class="elsevierStyleItalic">P</span><.05).</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Area \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="2" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Right Side</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="2" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Left Side</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Value of <span class="elsevierStyleItalic">P</span> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">No<span class="elsevierStyleItalic">.</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">No<span class="elsevierStyleItalic">.</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Vestibule 1<span class="elsevierStyleHsp" style=""></span>min \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">16 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">100 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">16 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">100 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NS \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Vestibule 7<span class="elsevierStyleHsp" style=""></span>min \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">16 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">100 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">16 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">100 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NS \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Septum 1<span class="elsevierStyleHsp" style=""></span>min \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleBold">75</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleBold">18.7</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleBold">.01</span> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Septum 7<span class="elsevierStyleHsp" style=""></span>min \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleBold">62.5</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleBold">13.5</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleBold">.01</span> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Inferior turbinate 1<span class="elsevierStyleHsp" style=""></span>min \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">14 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleBold">87.5</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleBold">0</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleBold">.001</span> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Inferior turbinate 7<span class="elsevierStyleHsp" style=""></span>min \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleBold">75</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleBold">0</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleBold">.001</span> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Inferior meatus 1<span class="elsevierStyleHsp" style=""></span>min \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NS \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Inferior meatus 7<span class="elsevierStyleHsp" style=""></span>min \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NS \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab179906.png" ] ] ] ] 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2023 March | 2 | 0 | 2 |
| 2021 February | 0 | 1 | 1 |
| 2021 January | 0 | 2 | 2 |
| 2020 December | 0 | 1 | 1 |
| 2020 November | 0 | 2 | 2 |
| 2020 October | 0 | 2 | 2 |
| 2020 July | 0 | 1 | 1 |
| 2020 May | 0 | 2 | 2 |
| 2020 March | 13 | 10 | 23 |
| 2020 February | 14 | 10 | 24 |
| 2020 January | 14 | 3 | 17 |
| 2019 December | 14 | 9 | 23 |
| 2019 November | 12 | 3 | 15 |
| 2019 October | 8 | 4 | 12 |
| 2019 September | 11 | 3 | 14 |
| 2019 August | 12 | 2 | 14 |
| 2019 July | 15 | 33 | 48 |
| 2019 June | 45 | 14 | 59 |
| 2019 May | 116 | 12 | 128 |
| 2019 April | 34 | 18 | 52 |
| 2019 March | 7 | 8 | 15 |
| 2019 February | 9 | 5 | 14 |
| 2019 January | 7 | 7 | 14 |
| 2018 December | 10 | 8 | 18 |
| 2018 November | 10 | 3 | 13 |
| 2018 October | 10 | 1 | 11 |
| 2018 May | 6 | 0 | 6 |
| 2018 April | 11 | 4 | 15 |
| 2018 March | 2 | 0 | 2 |
| 2018 February | 6 | 2 | 8 |
| 2018 January | 10 | 1 | 11 |
| 2017 December | 5 | 0 | 5 |
| 2017 November | 10 | 4 | 14 |
| 2017 October | 8 | 3 | 11 |
| 2017 September | 6 | 6 | 12 |
| 2017 August | 10 | 6 | 16 |
| 2017 July | 12 | 7 | 19 |
| 2017 June | 18 | 22 | 40 |
| 2017 May | 9 | 10 | 19 |
| 2017 April | 18 | 10 | 28 |
| 2017 March | 13 | 24 | 37 |
| 2017 February | 18 | 3 | 21 |
| 2017 January | 10 | 4 | 14 |
| 2016 December | 19 | 5 | 24 |
| 2016 November | 18 | 8 | 26 |
| 2016 October | 19 | 2 | 21 |
| 2016 September | 21 | 7 | 28 |
| 2016 August | 23 | 5 | 28 |
| 2016 July | 12 | 1 | 13 |
| 2016 June | 16 | 9 | 25 |
| 2016 May | 22 | 10 | 32 |
| 2016 April | 25 | 27 | 52 |
| 2016 March | 23 | 15 | 38 |
| 2016 February | 18 | 18 | 36 |
| 2016 January | 22 | 17 | 39 |
| 2015 December | 15 | 10 | 25 |
| 2015 November | 17 | 9 | 26 |
| 2015 October | 18 | 16 | 34 |
| 2015 September | 14 | 12 | 26 |
| 2015 August | 10 | 10 | 20 |
| 2015 July | 14 | 5 | 19 |
| 2015 June | 5 | 1 | 6 |
| 2015 May | 17 | 10 | 27 |
| 2015 April | 17 | 14 | 31 |
| 2015 March | 23 | 13 | 36 |
| 2015 February | 25 | 7 | 32 |
| 2015 January | 41 | 7 | 48 |
| 2014 December | 55 | 7 | 62 |
| 2014 November | 22 | 2 | 24 |
| 2014 October | 33 | 8 | 41 |
| 2014 September | 44 | 2 | 46 |
| 2014 August | 19 | 2 | 21 |
| 2014 July | 19 | 5 | 24 |
| 2014 June | 11 | 3 | 14 |
| 2014 May | 11 | 3 | 14 |
| 2014 April | 7 | 1 | 8 |
| 2014 March | 20 | 4 | 24 |
| 2014 February | 11 | 6 | 17 |
| 2014 January | 12 | 4 | 16 |
| 2013 December | 11 | 3 | 14 |
| 2013 November | 8 | 4 | 12 |
| 2013 October | 21 | 7 | 28 |
| 2013 September | 8 | 1 | 9 |
| 2013 August | 10 | 1 | 11 |
| 2013 July | 1 | 0 | 1 |
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