New reference nomograms for the study of ventricular size in preterm infants.

INTRODUCTION: Transfontanellar brain ultrasound is an essential tool for monitoring the size of the ventricles in preterm neonates and has many advantages over other alternative diagnostic techniques, including its accessibility and non-use of ionizing radiation. When considering the normal ventricular size, it is essential to have reference measurements based on age-matched populations. The objective of this article is to present our reference measures, based on a sample of preterm infants that we have studied. METHODS: A retrospective observational study was conducted. Measurements of the Levene index, frontal horn thickness, and Evans index were obtained in preterm neonates from 25 to 45 weeks, over a period of 5 years, between January 2016 and December 2020. After applying the exclusion criteria, a sample of 199 patients and 350 ultrasound scans were obtained. The independent samples t-test and the Mann-Whitney test were used for the comparison of samples. RESULTS: The distribution of the right and left Levene indices was normal (Shapiro-Wilk test with p = 0.16 and 0.05, respectively), unlike the thickness distribution of the frontal horns (p < 0.05 on both sides). No significant differences were detected between the sexes (p = 0.08). A linear correlation was found between the biparietal diameter and the Levene index. CONCLUSION: From the results obtained in our study, we present reference tables for ventricular size, with the 3rd, 25th, 50th, 75th, and 97th, being the first ones made in our country.

Actualización sobre el meningioma: correlación clínico-radiológica y radio-patológica / Update on meningioma: Clinical-radiological and radio-pathological correlation

Los meningiomas son tumores que se originan en las vellosidades aracnoideas y que constituyen la neoplasia no glial más común en el sistema nervioso central. Las manifestaciones clínicas asociadas al meningioma dependen, fundamentalmente, de su localización. La ubicación en la convexidad cerebral es las más frecuente, especialmente en lóbulos frontales, manifestándose con cefalea, alteraciones motoras, convulsiones e, incluso, con trastornos neurocognitivos. Existen 15 subtipos histológicos de meningioma y 3 grados histológicos. Dentro de estos, los grados 2 y 3 tienen un peor pronóstico y una mayor tasa de recurrencia, así como un comportamiento radiológico, por lo general, más agresivo. Aunque existen algunas características de imagen que pueden permitir demostrar un subtipo concreto, el diagnóstico definitivo siempre requerirá la confirmación histológica/molecular.(AU)

Meningiomas are tumors that originate in the arachnoid villi and are the most common non-glial neoplasm in the central nervous system. The clinical manifestations associated with meningioma depend, fundamentally, on its location. The location in the cerebral convexity is the most frequent, especially in the frontal lobes, manifesting with headache, motor disturbances, seizures and even neurocognitive disorders. There are 15 histologic subtypes of meningioma and three histologic grades. Within these, grades two and three have a worse prognosis and a higher rate of recurrence, as well as a radiological behavior that is generally more aggressive. Although there are some imaging features that can suggest a specific subtype, the definitive diagnosis will always require histological/molecular confirmation.(AU)

Update on meningioma: Clinical-radiological and radio-pathological correlation.

Meningiomas are tumors that originate in the arachnoid villi and are the most common non-glial neoplasm in the central nervous system. The clinical manifestations associated with meningioma depend, fundamentally, on its location. The location in the cerebral convexity is the most frequent, especially in the frontal lobes, manifesting with headache, motor disturbances, seizures and even neurocognitive disorders. There are 15 histologic subtypes of meningioma and three histologic grades. Within these, grades two and three have a worse prognosis and a higher rate of recurrence, as well as a radiological behavior that is generally more aggressive. Although there are some imaging features that can suggest a specific subtype, the definitive diagnosis will always require histological/molecular confirmation.

Estudio de coste-efectividad sobre la utilización de un tapón de hidrogel en las biopsias pulmonares guiadas por tomografía computarizada / Cost-effectiveness of hydrogel plugs in CT-guided lung biopsies

Objetivo: La utilización de un tapón de hidrogel reduce el número de neumotórax y la necesidad de tubos de drenaje pleural en las biopsias de pulmón guiadas por tomografía computarizada. Realizamos un estudio de coste-efectividad sobre su uso. Material y métodos: Se analizaron 171 biopsias de pulmón divididas en tres grupos: grupo 1 (n=22): punción aspirativa con aguja fina (PAAF) sin tapón de hidrogel; grupo 2 (n=89): PAAF con tapón, y grupo 3 (n=60): PAAF más biopsia con aguja gruesa (BAG) con tapón. Se calcularon costes totales (directos e indirectos) de los tres grupos. Se analizó el porcentaje de diagnósticos correctos, las ratios medias e incrementales y la opción más coste-efectiva. Resultados: Costes totales: grupo 1 = 1.261,28 + 52,65 = 1.313,93 Euros, grupo 2 = 1.201,36 + 67,25 = 1.268,61 euros, grupo 3 = 1.220,22 + 47,20 = 1.267,42 Euros. Porcentaje de diagnósticos correctos: grupo 1 = 77,3%, grupo 2 = 85,4% y grupo 3 = 95% (p = 0,04). Ratio medio de coste-efectividad: grupo 1 = 16,99, grupo 2 = 14,85 y grupo 3=13,34. Conclusiones: El grupo 3 fue la opción dominante, con la menor ratio media, lo cual demuestra que, en las biopsias de pulmón guiadas por TC, la opción más coste-efectiva es la realización de una PAAF y una BAG con la utilización del tapón de hidrogel deshidratado al final del procedimiento

Objective: Using a hydrogel plug decreases the number of cases of pneumothorax and reduces the need for pleural drainage tubes in CT-guided lung biopsies. We aimed to analyze the cost-effectiveness of using hydrogel plugs. Material and methods: We analyzed 171 lung biopsies divided into three groups: Group 1 (n=22): fine-needle aspiration cytology (FNAC) without hydrogel plugs; Group 2 (n=89): FNAC with hydrogel plugs; and Group 3 (n=60): FNAC plus core-needle biopsy (CNB) with hydrogel plugs. We calculated the total costs (direct and indirect) in the three groups. We analyzed the percentage of correct diagnoses, the average and incremental rations, and the most cost-effective option. Results: Total costs: Group 1 = 1,261.28 + 52.65 = euros 1,313.93; Group 2 = 1,201.36 + 67.25 = Euros 1,268.61; Group 3 = 1,220.22 + 47.20 = Euros 1,267.42. Percentage of correct diagnoses: Group 1 = 77.3%, Group 2 = 85.4%, and Group 3 = 95% (p = 0.04). Average cost-effectiveness ratio: Group 1 = 16.99; Group 2 = 14.85; and Group 3 = 13.34. Conclusions: Group 3 was the best option, with the lowest average cost-effectiveness ratio; therefore, the most cost-effective approach is to do FNAC and CNB using a dehydrated hydrogel plug at the end of the procedure

Cost-effectiveness of hydrogel plugs in CT-guided lung biopsies. / Estudio de coste-efectividad sobre la utilización de un tapón de hidrogel en las biopsias pulmonares guiadas por tomografía computarizada.

OBJECTIVE: Using a hydrogel plug decreases the number of cases of pneumothorax and reduces the need for pleural drainage tubes in CT-guided lung biopsies. We aimed to analyze the cost-effectiveness of using hydrogel plugs. MATERIAL AND METHODS: We analyzed 171 lung biopsies divided into three groups: Group 1 (n=22): fine-needle aspiration cytology (FNAC) without hydrogel plugs; Group 2 (n=89): FNAC with hydrogel plugs; and Group 3 (n=60): FNAC plus core-needle biopsy (CNB) with hydrogel plugs. We calculated the total costs (direct and indirect) in the three groups. We analyzed the percentage of correct diagnoses, the average and incremental rations, and the most cost-effective option. RESULTS: Total costs: Group 1 = 1,261.28 + 52.65 = € 1,313.93; Group 2 = 1,201.36 + 67.25 = € 1,268.61; Group 3 = 1,220.22 + 47.20 = € 1,267.42. Percentage of correct diagnoses: Group 1 = 77.3%, Group 2 = 85.4%, and Group 3 = 95% (p = 0.04). Average cost-effectiveness ratio: Group 1 = 16.99; Group 2 = 14.85; and Group 3 = 13.34. CONCLUSIONS: Group 3 was the best option, with the lowest average cost-effectiveness ratio; therefore, the most cost-effective approach is to do FNAC and CNB using a dehydrated hydrogel plug at the end of the procedure.

Estudio de costo-efectividad de la biopsia mamaria asistida por vacío versus biopsia con aguja gruesa o arpón / The cost effectiveness of vacuum-assisted versus core-needle versus surgical biopsy of breast lesions

Objetivo. Realizar estudio de costo-efectividad de la biopsia por aspiración al vacío (BAV) (9 G) guiada por estereotaxia vertical o ecografía comparada con biopsia con aguja gruesa (BAG) (14 G) y biopsia con arpón. Material y métodos. Analizamos 997 biopsias mamarias (181 BAV, 626 BAG y 190 arpones). Calculamos costes totales (directos e indirectos) de los tres tipos de biopsia. No calculamos costes intangibles. El efecto a medir fue el "porcentaje de diagnósticos correctos" obtenidos con cada una de las técnicas. Calculamos los ratios medios de los tres tipos de biopsias e identificamos la opción dominante más costo-efectiva. Resultados. Costes totales de BAG 225,09 Euros, de BAV 638,90 Euros y de biopsia con arpón 1780,01 Euros. Porcentaje de diagnósticos correctos globales con BAG 91,81%, BAV 94,03% y biopsia con arpón 100%, sin diferencias significativas (p=0,3485). En microcalcificaciones, los porcentajes de diagnósticos correctos fueron con BAG 50% y con BAV 96,77%, p<0,0001. En nódulos tampoco hubo diferencias significativas. El ratio medio costo-efectividad considerando todas las lesiones en conjunto, fue para BAG 2,45, BAV 6,79 y arpón 17,80. Conclusión. La BAG fue la opción dominante para el diagnóstico de lesiones mamarias sospechosas de malignidad en general. En el caso de las microcalcificaciones, el bajo porcentaje de diagnósticos de la BAG (50%) desaconsejan su uso y colocan a la BAV como técnica de elección; la BAV es, además, más costo-efectiva que el arpón, que es la otra técnica indicada para biopsiar microcalcificaciones (AU)

Objectives. To determine the cost effectiveness of breast biopsy by 9G vacuum-assisted guided by vertical stereotaxy or ultrasonography in comparison with breast biopsy by 14G core-needle biopsy and surgical biopsy. Material and methods. We analyzed a total of 997 biopsies (181 vacuum-assisted, 626 core, and 190 surgical biopsies). We calculated the total costs (indirect and direct) of the three types of biopsy. We did not calculate intangible costs. We measured the percentage of correct diagnoses obtained with each technique. To identify the most cost-effective option, we calculated the mean ratios for the three types of biopsies. Results. Total costs were Euros 225.09 for core biopsy, Euros 638.90 for vacuum-assisted biopsy, and Euros 1780.01 for surgical biopsy. The overall percentage of correct diagnoses was 91.81% for core biopsy, 94.03% for vacuum-assisted biopsy, and 100% for surgical biopsy; however, these differences did not reach statistical significance (p=0.3485). For microcalcifications, the percentage of correct diagnoses was 50% for core biopsy and 96.77% for vacuum-assisted biopsy (p<0.0001). For nodules, there were no significant differences among techniques. The mean cost-effectiveness ratio considering all lesions was 2.45 for core biopsy, 6.79 for vacuum-assisted biopsy, and 17.80 for surgical biopsy. Conclusion. Core biopsy was the dominant option for the diagnosis of suspicious breast lesions in general. However, in cases with microcalcifications, the low percentage of correct diagnoses achieved by core biopsy (50%) advises against its use in this context, where vacuum-assisted biopsy would be the technique of choice because it is more cost-effective than surgical biopsy, the other technique indicated for biopsying microcalcifications (AU)

The cost effectiveness of vacuum-assisted versus core-needle versus surgical biopsy of breast lesions. / Estudio de costo-efectividad de la biopsia mamaria asistida por vacío versus biopsia con aguja gruesa o arpón.

OBJECTIVES: To determine the cost effectiveness of breast biopsy by 9G vacuum-assisted guided by vertical stereotaxy or ultrasonography in comparison with breast biopsy by 14G core-needle biopsy and surgical biopsy. MATERIAL AND METHODS: We analyzed a total of 997 biopsies (181 vacuum-assisted, 626 core, and 190 surgical biopsies). We calculated the total costs (indirect and direct) of the three types of biopsy. We did not calculate intangible costs. We measured the percentage of correct diagnoses obtained with each technique. To identify the most cost-effective option, we calculated the mean ratios for the three types of biopsies. RESULTS: Total costs were €225.09 for core biopsy, €638.90 for vacuum-assisted biopsy, and €1780.01 for surgical biopsy. The overall percentage of correct diagnoses was 91.81% for core biopsy, 94.03% for vacuum-assisted biopsy, and 100% for surgical biopsy; however, these differences did not reach statistical significance (p=0.3485). For microcalcifications, the percentage of correct diagnoses was 50% for core biopsy and 96.77% for vacuum-assisted biopsy (p<0.0001). For nodules, there were no significant differences among techniques. The mean cost-effectiveness ratio considering all lesions was 2.45 for core biopsy, 6.79 for vacuum-assisted biopsy, and 17.80 for surgical biopsy. CONCLUSION: Core biopsy was the dominant option for the diagnosis of suspicious breast lesions in general. However, in cases with microcalcifications, the low percentage of correct diagnoses achieved by core biopsy (50%) advises against its use in this context, where vacuum-assisted biopsy would be the technique of choice because it is more cost-effective than surgical biopsy, the other technique indicated for biopsying microcalcifications.

Puesta al día en el estudio radiológico de la tuberculosis pulmonar / Update on the radiological study of pulmonary tuberculosis

La tuberculosis ha mostrado un resurgimiento en los últimos años, fenómeno que se ha atribuido a factores como el aumento de la migración y la epidemia del virus de la inmunodeficiencia humana. La tuberculosis pulmonar primaria se manifiesta desde el punto de vista radiológico con afectación parenquimatosa, linfadenopatías, derrame pleural o enfermedad miliar. En la forma posprimaria, el hallazgo radiológico más precoz son los nodulillos y las lesiones ramificadas centrolobulillares, que aumentan de tamaño y confluyen para dar consolidaciones parcheadas, mal definidas. La presencia de cavitaciones es muy característica de enfermedad activa. El objetivo de este trabajo es describir los hallazgos radiológicos de la tuberculosis pulmonar y sus complicaciones (AU)

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Preferencias en el formato de cuestionarios y en el uso de Internet en escolares / Preferences in the format of questionnaires and use of the Internet by schoolchildren

OBJETIVOS: Describir las preferencias para responder cuestionarios vía web en población infantil escolarizada; y analizar la actitud sobre el uso de Internet para comunicarse con los profesionales de salud. MÉTODOS: Estudio transversal de la población escolar de Palafolls (Barcelona, n=923) en octubre y noviembre de 2013. Los participantes contestaron las versiones web y en papel en un día de clase, en orden aleatorizado y con un intervalo mínimo de 2horas. Se recogieron las preferencias por una u otra versión, y la intención de compartir información con los profesionales de salud. Se calcularon porcentajes de uso y actitudes, y se ajustaron modelos de regresión logística. RESULTADOS: Participación de 77% (n=715). El 42,4% (38,7-46,0) declaró preferir la versión web y el 20,6% (17,6-23,6) prefirió la versión papel. Los de mayor edad (odds ratio [OR]=0,89; 0,84-0,95 para la edad), y los de familias con nivel de estudios secundarios (OR=0,63; 0,43-0,93) o universitarios (OR=0,61; 0,38-0,97) presentaron menor probabilidad de preferir la versión web. Los varones (OR=1,55; 1,10-2,16), y los que declararon hábitos sedentarios (OR=1,78; 1,06-3,0) presentaron mayor probabilidad de preferir la versión web. La puntuación más elevada (mejor) en calidad de vida (OR=1,03; 1,01-1,05) y no declarar hábitos sedentarios (OR=0,33; 0,15-0,73) se asoció con la actitud positiva para compartir información con los profesionales de salud. CONCLUSIONES: Los niños más jóvenes declaran preferir la versión web. Aunque el uso de Internet es muy generalizado, está poco extendido para comunicarse con los profesionales sanitarios

OBJECTIVES: To describe the preferences to complete questionnaires via the internet by schoolchildren, as well as to analyze the attitude towards the use of internet to communicate with health professionals. METHODS: Cross-sectional study of a school population in Palafolls (Barcelona, n=923) was conducted in October and November 2013. Participants completed both internet and paper versions on a single school day, in random order, and with at least an interval of 2hours. Preferences to answer internet vs paper version were recorded, along with the willingness to share information with health professionals. Percentages of use preferences and attitudes were estimated, and logistic regression models were fitted to analyze the association with the preferences and willingness to share information with health professionals. RESULTS: Participation rates were 77% (n=715), of whom 42.4% (38.7 to 46.0) preferred the internet version, and 20.6% (17.6 to 23.6) the paper version. Older children (odds ratio [OR] = 0.89, 0.84 to 0.95 for age), and those from families with secondary school (OR = 0.63, 0.43 to 0.93), and university degree (OR = 0.61, 0.38 to 0.97) were less likely to prefer the internet version, while boys (OR = 1.55, 1.10 to 2.16) and those children reporting sedentary habits (OR = 1.78, 1.06 to 3.0) were more likely to prefer the internet version. Those scoring higher quality of life (OR = 1.03, 1.01-1.05) and not reporting sedentary habits (OR = 0.33, 0.15 to 0.73) were factors associated with a positive attitude to share information with health professionals. CONCLUSIONS: Younger children prefer to use the internet. Although Internet use is very widespread, it is less used to communicate with health professionals

[Update on the radiological study of pulmonary tuberculosis]. / Puesta al día en el estudio radiológico de la tuberculosis pulmonary.

Tuberculosis has made a comeback in recent years. This upsurge has been attributed to factors such as increased immigration and the human immunodeficiency virus epidemic. Primary pulmonary tuberculosis manifests radiologically with parenchymal involvement, lymph node involvement, pleural effusion, and/or miliary disease. In post-primary tuberculosis, the earliest radiological sign is small nodules and branching centrilobular lesions that increase in size and coalesce to form ill-defined patchy consolidations; cavitations are very characteristic of active disease. The aim of this article is to describe the radiologic findings for pulmonary tuberculosis and its complications.

Induction of somatic embryogenesis in explants of shoot cultures established from adult Eucalyptus globulus and E. saligna†×†E. maidenii trees.

A reproducible procedure for induction of somatic embryogenesis (SE) from adult trees of Eucalyptus globulus Labill. and the hybrid E. saligna Smith × E. maidenii has been developed for the first time. Somatic embryos were obtained from both shoot apex and leaf explants of all three genotypes evaluated, although embryogenic frequencies were significantly influenced by the species/genotype, auxin and explant type. Picloram was more efficient for somatic embryo induction than naphthaleneacetic acid (NAA), with the highest frequency of induction being obtained in Murashige and Skoog medium containing 40 µM picloram and 40 mg l(-1) gum Arabic, in which 64% of the shoot apex explants and 68.8% of the leaf explants yielded somatic embryos. The embryogenic response of the hybrid was higher than that of the E. globulus, especially when NAA was used. The cultures initiated on picloram-containing medium consisted of nodular embryogenic structures surrounded by a mucilaginous coating layer that emerged from a watery callus developed from the initial explants. Cotyledonary somatic embryos were differentiated after subculture of these nodular embryogenic structures on a medium lacking plant growth regulators. Histological analysis confirmed the bipolar organization of the somatic embryos, with shoot and root meristems and closed procambial tissue that bifurcated into small cotyledons. The root pole was more differentiated than the shoot pole, which appeared to be formed by a few meristematic layers. Maintenance of the embryogenic lines by secondary SE was attained by subculturing individual cotyledonary embryos or small clusters of globular and torpedo embryos on medium with 16.11 µM NAA at 4- to 5-week intervals. Somatic embryos converted into plantlets after being transferred to liquid germination medium although plant regeneration remained poor.

[Preferences in the format of questionnaires and use of the Internet by schoolchildren]. / Preferencias en el formato de cuestionarios y en el uso de Internet en escolares.

OBJECTIVES: To describe the preferences to complete questionnaires via the internet by schoolchildren, as well as to analyze the attitude towards the use of internet to communicate with health professionals. METHODS: Cross-sectional study of a school population in Palafolls (Barcelona, n=923) was conducted in October and November 2013. Participants completed both internet and paper versions on a single school day, in random order, and with at least an interval of 2 hours. Preferences to answer internet vs paper version were recorded, along with the willingness to share information with health professionals. Percentages of use preferences and attitudes were estimated, and logistic regression models were fitted to analyze the association with the preferences and willingness to share information with health professionals. RESULTS: Participation rates were 77% (n=715), of whom 42.4% (38.7 to 46.0) preferred the internet version, and 20.6% (17.6 to 23.6) the paper version. Older children (odds ratio [OR]=0.89, 0.84 to 0.95 for age), and those from families with secondary school (OR=0.63, 0.43 to 0.93), and university degree (OR=0.61, 0.38 to 0.97) were less likely to prefer the internet version, while boys (OR=1.55, 1.10 to 2.16) and those children reporting sedentary habits (OR=1.78, 1.06 to 3.0) were more likely to prefer the internet version. Those scoring higher quality of life (OR=1.03, 1.01-1.05) and not reporting sedentary habits (OR=0.33, 0.15 to 0.73) were factors associated with a positive attitude to share information with health professionals. CONCLUSIONS: Younger children prefer to use the internet. Although Internet use is very widespread, it is less used to communicate with health professionals.

Melanoma maligno gastrointestinal en paciente albino: a propósito de un caso

Los albinos tienen predisposición al padecimiento de determinados tipos de cáncer cutáneo, pero el melanoma no es común. Entre los pocos artículos que documentan su aparición en estos pacientes, la afección gastrointestinal por melanoma aparece con relativa frecuencia, ya sea en forma de tumor primario o metástasis. Se presenta el caso de una paciente mujer de 70 años con una lesión gástrica y otra intestinal, detectadas mediante tomografía computada. El estudio anatomopatológico fue compatible con el diagnóstico de melanoma amelanótico. Pese a su escasa incidencia en albinos, el melanoma es una opción que no puede descartarse. Es importante, además, revisar los diferentes componentes del tracto gastrointestinal ante la existencia (o no) de un melanoma primario conocido.(AU)

Albinos are predisposed to suffer certain types of skin cancer, but not usually melanoma, with just a few reports documenting it .Gastrointestinal tract is a relatively frequent site of melanoma occurrence, weather as a primary tumour or metastasis. We report a case of a 70 year-old female patient who underwent a computed tomography where a gastric and a bowel tumor were found. The pathology study was compatible with the diagnosis of an amelanotic melanoma. Despite that the diagnosis of melanoma in albine patients is a rare finding, it must be considered. It is also important to search through the digestive system even if there is no primary melanoma known.(AU)

Melanoma maligno gastrointestinal en paciente albino: a propósito de un caso / Gastrointestinal melanoma in an albino patient: Report of a case

Los albinos tienen predisposición al padecimiento de determinados tipos de cáncer cutáneo, pero el melanoma no es común. Entre los pocos artículos que documentan su aparición en estos pacientes, la afección gastrointestinal por melanoma aparece con relativa frecuencia, ya sea en forma de tumor primario o metástasis. Se presenta el caso de una paciente mujer de 70 años con una lesión gástrica y otra intestinal, detectadas mediante tomografía computada. El estudio anatomopatológico fue compatible con el diagnóstico de melanoma amelanótico. Pese a su escasa incidencia en albinos, el melanoma es una opción que no puede descartarse. Es importante, además, revisar los diferentes componentes del tracto gastrointestinal ante la existencia (o no) de un melanoma primario conocido...

Pulsed dye laser treatment for facial flat warts.

The facial flat wart is not only a contagious viral disease, but also a cause of a distressing cosmetic problem. Although there are many therapeutic options, including salicylic acid, imiquimod, cryotherapy, retinoids, intralesional immunotherapy, and topical 5-aminolevulinic acid photodynamic therapy among others, no monotherapy has been proved to achieve complete remission in every case. Treatment with pulsed dye laser (PDL) seems to be a promising therapeutic option. To assess the efficacy and safety of PDL in a series of patients with viral flat warts on the face, in this prospective study, 32 patients were treated with PDL at 595-nm wavelength, a laser energy density of 9 or 14 J/cm(2) with a spot size of 7 or 5 mm, respectively, with air cooling and a pulse duration of 0.5 millisecond. A complete response was noted in 14 patients (44%), and an excellent response was observed in 18 patients (56%) with 1-year follow-up, with only four recurrences. No significant side effects were reported except intense transitory purpuric response. We consider that PDL is a good option of treatment for flat warts on the face due to its good clinical results, fast response, and low incidence of side effects.

Comparative assessment of PDE 4 and 7 inhibitors as therapeutic agents in experimental autoimmune encephalomyelitis.

BACKGROUND AND PURPOSE: PDE4 inhibition suppresses experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). However, side effects hinder PDE4 inhibitors clinical use. PDE7 inhibition might constitute an alternative therapeutic strategy, but few data about the anti-inflammatory potential of PDE7 inhibitors are currently available. We have used the EAE model to perform a comparative evaluation of PDE4 and PDE7 inhibition as strategies for MS treatment. EXPERIMENTAL APPROACH: Two PDE7 inhibitors, the sulfonamide derivative BRL50481 and the recently described quinazoline compound TC3.6, were assayed to modulate EAE in SJL mice, in comparison with the well-known PDE4 inhibitor Rolipram. We evaluated clinical signs, presence of inflammatory infiltrates in CNS and anti-inflammatory markers. We also analysed the effect of these inhibitors on the inflammatory profile of spleen cells in vitro. KEY RESULTS: TC3.6 prevented EAE with efficacy similar to Rolipram, while BRL50481 had no effect on the disease. Differences between both PDE7 inhibitors are discussed. Data from Rolipram and TC3.6 showed that PDE4 and PDE7 inhibition work through both common and distinct pathways. Rolipram administration caused an increase in IL-10 and IL-27 expression which was not found after TC3.6 treatment. On the other hand, both inhibitors reduced IL-17 levels, prevented infiltration in CNS and increased the expression of the T regulator cell marker Foxp3. CONCLUSIONS AND IMPLICATIONS: These results provide new information about the effects of Rolipram on EAE, underline PDE7 inhibition as a new therapeutic target for inflammatory diseases and show the value of TC3.6 to prevent EAE, with possible consequences for new therapeutic tools in MS.