Modelo integral de entrenamiento microquirúrgico y neuroendovascular con placenta humana / Comprehensive microsurgical and neuroendovascular training model with human placenta

Introducción: La neurocirugía vascular, tanto la microquirúrgica como endovascular, ha progresado significativamente en el tratamiento de la patología cerebrovascular. Sin embargo, en una considerable proporción de casos este tipo de patología no puede ser resuelta definitivamente mediante un único abordaje. Por lo cual consideramos que el neurocirujano en formación debe capacitarse con ambas técnicas.Se describe un modelo de entrenamiento en microcirugía y en nociones básicas del material y técnica neuroendovascular, utilizando placenta humana y recursos de baja complejidad. Material y método: Se utilizaron 20 placentas humanas, instrumental y sutura de uso habitual en microcirugía, microscopio quirúrgico Newton®XX1, material para procedimientos endovasculares; equipo de radioscopia (arco en C Phillips BV Pulsera®), un cráneo óseo y un cabezal de fijación tipo Sugita® adaptado a su uso en laboratorio. Los ejercicios consistieron en: 1. Disección y exposición de los vasos arteriales y venosos del corion; 2. Anastomosis término-terminal, termino-lateral y latero-lateral; 3. Generación de aneurismas laterales, de bifurcación o trifurcación; 4. Creación de bypass extra-intracraneano; 5. Clipado de los aneurismas en superficie y dentro del cráneo; 6. Control angiográfico pre y post clipado. 7. Embolización con coils de los aneurismas experimentales y de vasos placentarios con partículas de Spongostan®. Resultados: Aunque los vasos tienen una estructura y consistencia diferentes a los habituales para el neurocirujano, la placenta ofrece una variabilidad de calibres y formatos donde practicar los diferentes ejercicios. Conclusión: El entrenamiento en técnicas microquirúrgicas y neurointervencionistas puede ser realizado en modelos placentarios de simulación, que permiten el desarrollo háptico progresivo previo a la realización de un procedimiento in vivo.

Objective: Describe a training model in microsurgery and neuroendovascular surgery, using human placenta and low complexity resources. Material and methods: 20 human placentas, instruments and sutures were used in microsurgery, Newton XX1 surgical microscope, material for endovascular procedures; radioscopy equipment (C-arch Phillips BV Pulsera), a bony skull and a Sugita head adapted for laboratory use. The exercises consisted of: 1. Dissection and exposure of the arterial and venous vessels of the chorion; 2. End-to-end, end-to-side, side-to-side anastomosis; 3. Generation of lateral, bifurcation or trifurcation aneurysms; 4. Creation of extra-intracranial bypass; 5. Clipping of aneurysms on the surface and inside the skull; 6. Pre and post clipping angiographic control. 7. Coil embolization of experimental aneurysms and placental vessels embolization with spongostan particles. Results: Although the vessels have a different structure and consistency than usual for the neurosurgeon, the placenta offers a variability of sizes and formats to practice the different exercises. Conclusion: Training in microsurgical and neurointerventionist techniques can be carried out in placental models, which allow progressive haptic development prior to performing an in vivo procedure.

Impact of Melatonin Supplementation in Women with Unexplained Infertility Undergoing Fertility Treatment.

Unexplained infertility occurs when common causes for a couple's inability to conceive have been excluded. Although origins of idiopathic infertility are still unclear, factors, such as an altered oxidative balance, are believed to be involved. Melatonin is an outstanding antioxidant reportedly present in the follicular fluid (FF), which has been suggested as a useful tool in the management of human fertility. Herein, we observed that intrafollicular concentrations of melatonin were blunted in women with unexplained infertility (UI), which was associated with a marked oxidative imbalance in UI patients' FF. Based on these findings, this randomized pilot study was aimed at assessing whether exogenous melatonin ameliorated oxidative stress and improved in vitro fertilization (IVF) success rates in UI. Thus, 3 mg/day or 6 mg/day of melatonin were given to UI patients for a period spanning from the first appointment to control ovarian stimulation until the day of follicular puncture. Our results indicate that melatonin supplementation, irrespective of the two doses tested, ameliorated intrafollicular oxidative balance and oocyte quality in UI patients, and that this translated into a slight increase in the rate of pregnancies/live births. Therefore, although the indoleamine has shown therapeutic potential in this clinical setting, larger clinical trials in populations with different backgrounds are encouraged to corroborate the usefulness of melatonin.

Melatonin diminishes oxidative damage in sperm cells, improving assisted reproductive techniques.

Sperm preparation procedures are a potential generator of oxidative stress-induced DNA damage, which leads to a dramatic drop in fertility. An increasing number of studies suggest that melatonin reduces the oxidative stress induced by manipulation. However, very little is known about the preservative role of melatonin in sperm preparation medium during assisted reproduction procedures. For this aim to be achieved, semen was divided into two fractions and preincubated with and without 1 mM melatonin. Afterwards, both fractions were divided into two subfractions to perform swim-up in the presence and absence of 1 mM melatonin. Labeling with anti-CD46 and antiactive caspase-3 allowed the monitoring of acrosome reaction and apoptosis by flow cytometry. Sperm DNA fragmentation and compaction were analyzed through propidium iodide staining. The normozoospermic and oligozoospermic samples that were preincubated with melatonin underwent a significant increase in the ratio of adequate spermatozoa and a reduction of caspase-3 activation. Additionally, preincubation with melatonin enhanced the migration of sperm cells with compacted DNA in oligozoospermic samples (P < 0.05) and prevented DNA fragmentation in normozoospermic samples (P < 0.05). In light of the current results, the cytoprotective capacity and innocuousness of melatonin make it a great candidate to be applied in assisted reproduction techniques in order to prevent triaogenic oxidative damage.

Metástasis en la mama de tumores extramamarios. Presentación de casos clínicos y revisión bibliográfica / Metastases to the breast of extramammary malignancies

Las metástasis en la mama son raras y representan solo el 0,5 al 2% de todas las neoplasias malignas de la misma. Cualquier tumor maligno puede metastatizar en la mama, pero los más frecuentemente reportados corresponden, entre otros, a linfoma, melanoma, cáncer de pulmón, de ovario, gástrico, de próstata y renal. Objetivo: El presente trabajo tiene como objetivo analizar nuestra experiencia en el hallazgo de nódulos mamarios que simulaban tumores benignos o malignos de la mama y resultaron ser metástasis de otros órganos. Se evaluó la forma de presentación y las características clínico-patológicas e imagenológicas de dichos casos. Material y método: Se analizaron en forma retrospectiva las historias clínicas de las pacientes operadas en el Hospital Central de San Isidro y en el Centro Mamario del Hospital Universitario Austral entre agosto de 2009 y agosto de 2014. Seidentificaron 5 casos de metástasis en la mama provenientes de tumores primarios de otros órganos. Resultados: Sobre un total de 5 casos de metástasis en la mama, todos fueron del sexofemenino. Las edades oscilaron entre 59 y 72 años (promedio 64 años). Observamos nódulos palpables al momento de la consulta, de rápido crecimiento, sin retracción de piel o pezón. Con respecto a las imágenes mamarias, se evidenciaron nódulos de bordes predominantemente definidos en 4 casos (66,6%) y, en dos de ellos, polilobulados (33,3%). No se evidenciaron microcalcificaciones ni espículas en ninguno de los casos. Discusión: Las metástasis mamarias son poco frecuentes. Clínica e imagenológicamente son de difícil diagnóstico, por lo que se destaca la importancia de tener en cuenta los antecedentes clínicos de los pacientes para realizar su diagnóstico diferencial...

Exogenous melatonin supplementation prevents oxidative stress-evoked DNA damage in human spermatozoa.

Reactive oxygen species (ROS) are essential for sperm physiological functions such as capacitation, hyperactivation, and acrosome reaction, on the one hand, and for stimulating the apoptotic processes involved in the regulation of spermatogenesis, on the other hand. However, the imbalance between production and removal of ROS leads to oxidative stress, which is referred to as one of the main factors involved in male infertility. The pineal hormone melatonin, given its low toxicity and well-known antioxidant capacity, could be an excellent candidate to improve sperm quality. For this reason, the objective of the present work was to analyze whether long-term supplementation with melatonin to infertile men affects human sperm quality and the quality of the embryos retrieved from their couples. Our findings showed that the daily supplementation of 6 mg melatonin, as early as after 45 days of treatment, produced an increase in melatonin endogenous levels, indirectly measured as urinary 6-sulfatoxymelatonin (aMT6-s), an enhancement of both urinary and seminal total antioxidant capacity, and a consequent reduction in oxidative damage caused in sperm DNA. Moreover, couples whose men were given melatonin showed a statistically significant increase in the percentage of grade A (embryo with blastomeres of equal size; no cytoplasmic fragmentation), B (embryo with blastomeres of equal size; minor cytoplasmic fragmentation), and C (embryo with blastomeres of distinctly unequal size; significant cytoplasmic fragmentation) embryos at the expense of grade D (embryo with blastomeres of equal or unequal size; severe or complete fragmentation.) embryos which were clearly reduced. In summary, melatonin supplementation improves human sperm quality, which is essential to achieve successful natural and/or assisted reproduction outcome.

Fascitis palmr asociada a leucemia mieloide crónica / Palmar fascitis associated with chronic myeloid leukemia

El síndrome de fascitis palmar con poliartritis (PFPAS) es un trastorno paraneoplásico infrecuente. Consiste en artritis generalizada de la mano, eritema, tumefacción, rigidez y engrosamiento de la fascia palmar con contracturas progresivas en flexión de los dedos, yse asocia a una enfermedad maligna subyacente. Presentamos el caso de una mujer de 75 años de edad que presentó placas induradas eritemato-violáceaspruriginosas y levemente dolorosas en ambas palmas, con tumefaccióny retracción en flexión de los dedos asociado a artralgias en ambas muñecas.El estudio de la médula ósea confirmó el diagnóstico de leucemia mieloide crónica...

Exploratory, randomized, double-blind, placebo-controlled study on the effects of Bifidobacterium infantis natren life start strain super strain in active celiac disease.

BACKGROUND/AIMS: The aim of this exploratory trial was to establish if the probiotic Bifidobacterium natren life start (NLS) strain strain may affect the clinical course and pathophysiological features of patients with untreated celiac disease (CD). Positive findings would be helpful in directing future studies. METHODS: Twenty-two adult patients having 2 positives CD-specific tests were enrolled. Patients were randomized to receive 2 capsules before meals for 3 weeks of either Bifidobacterium infantis natren life start strain super strain (Lifestart 2) (2×10(9) colony-forming units per capsule) (n = 12) or placebo (n = 10), whereas they also consumed at least 12 g of gluten/day. A biopsy at the end of the trial confirmed CD in all cases. The primary outcome was intestinal permeability changes. Secondary endpoints were changes in symptoms and the Gastrointestinal Symptom Rating Scale, and in immunologic indicators of inflammation. RESULTS: The abnormal baseline intestinal permeability was not significantly affected by either treatment. In contrast to patients on placebo, those randomized to B. infantis experienced a significant improvement in Gastrointestinal Symptom Rating Scale (P = 0.0035 for indigestion; P = 0.0483 for constipation; P = 0.0586 for reflux). Final/baseline IgA tTG and IgA DGP antibody concentration ratios were lower in the B. infantis arm (P = 0.055 for IgA tTG and P = 0.181 for IgA DGP). Final serum macrophage inflammatory protein-1ß increased significantly (P < 0.04) only in patients receiving B. infantis. The administration of B. infantis was safe. CONCLUSIONS: The study suggests that B. infantis may alleviate symptoms in untreated CD. The probiotic produced some immunologic changes but did not modify abnormal intestinal permeability. Further studies are necessary to confirm and/or expand these observations.

Melatonin protects human spermatozoa from apoptosis via melatonin receptor- and extracellular signal-regulated kinase-mediated pathways.

OBJECTIVE: To evaluate whether the protective effect of melatonin on H2O2-induced caspase activation and DNA fragmentation depends on the interaction between melatonin and its surface receptors. DESIGN: Laboratory study. SETTING: Center for assisted human reproduction at a Spanish hospital. PATIENT(S): Twenty-one healthy donors. INTERVENTION(S): Human spermatozoa were treated with increasing concentrations of hydrogen peroxide (H2O2; 1 µM, 10 µM, 100 µM, 1 mM) and preincubated with 1 mM melatonin. MAIN OUTCOMES MEASURE(S): Activation of caspase-3 and -9 as well as DNA fragmentation were examined by fluorescence methods. RESULT(S): Our findings showed that H2O2 induced a significant increase in caspase-9 and caspase-3, which was dose independent. Conversely, pretreatment with melatonin reduced H2O2-mediated caspase activation in a dose-dependent way. Moreover, the antiapoptotic effects of melatonin in ejaculated human spermatozoa may involve membrane melatonin receptor MT1. In addition, we found that the survival-promoting pathway extracellular signal-regulated kinase (ERK) is likely to have a role in the protective actions of melatonin in ejaculated human spermatozoa. Finally, we confirmed these results further by demonstrating that melatonin prevention of H2O2-induced DNA fragmentation is dependent on both MT1 receptor and ERK signaling. CONCLUSION(S): These results indicate that the stimulation with melatonin triggers a set of events culminating in cell death prevention in ejaculated human spermatozoa.

Granuloma actínico / Actinic granuloma

El granuloma actínico es una rara afección de la piel que se desarrolla en general en áreas expuestas al sol. Su patogénesis no es clara.La teoría más aceptada es la implicancia de la radiación solar como factor disparador. Típicamente la enfermedad se presenta en individuos mayores de 30 años con historia de exposición solar. Se manifiesta con lesiones anulares de bordes elevados y atrofia central,asintomáticas, con poca tendencia a la involución. Se han probado múltiples terapéuticas con éxito variado. Esta entidad poco frecuente fue descripta por primera vez en 1975 por O`Brien. Presentamos dos pacientes con granuloma actínico. El primero correspondió a una mujer de 83 años de edad con una lesión en pómulo izquierdo. El segundo a un varón de 70 años con una gran lesión que se extendía desde el epigastrio hasta las clavículas.

Actinic granuloma is a rare skin disorder usually developing uponsun-exposed areas. While its pathogenesis is unclear, the acceptedhypothesis maintains that solar radiation is the triggering factor.Typically the disease develops in individuals over 30 years of age witha history of sun exposure, showing annular lesions with raised bordersand central atrophy, asymptomatic, with little tendency to regression.Multiple therapies have been tested with variable response. Thisuncommon entity was described for the first time in 1975 by O’Brien.We present two patients with actinic granuloma. The first onecorresponded to an 83 years-old woman with a lesion on the leftcheek. The second one was a 70 years-old male with a large lesion thatextended from the epigastrium to the collar bones.

The correlation between urinary 5-hydroxyindoleacetic acid and sperm quality in infertile men and rotating shift workers.

BACKGROUND: Serotonin is a neurotransmitter that modulates a wide range of neuroendocrine functions. However, excessive circulating serotonin levels may induce harmful effects in the male reproductive system. The objective of this study was to evaluate whether the levels of urinary 5-hydroxyindoleacetic acid (5-HIIA), a major serotonin metabolite, correlate with different classical seminal parameters. METHODS: Human ejaculates were obtained from 40 men attending infertility counselling and rotating shift workers by masturbation after 4-5 days of abstinence. Urinary 5- HIIA concentration was quantified by using a commercial ELISA kit. Forward motility was assessed by a computer-aided semen analysis (CASA) system. Sperm concentration was determined using the haemocytometer method. Sperm morphology was evaluated after Diff-Quik staining, while sperm vitality was estimated after Eosin-Nigrosin vital staining. RESULTS: Our results show that urinary 5-HIIA levels obtained from a set of 20 volunteers negatively correlated with sperm concentration, forward motility, morphology normal range and sperm vitality. On the other hand, we checked the relationship between male infertility and urinary 5-HIIA levels in 20 night shift workers. Thus, urinary 5-HIIA levels obtained from 10 recently-proven fathers were significantly lower than those found in 10 infertile males. Additionally, samples from recent fathers exhibited higher sperm concentration, as well as better forward motility and normal morphology rate. CONCLUSIONS: In the light of our findings, we concluded that high serotonin levels, indirectly measured as urinary 5-HIIA levels, appear to play a role as an infertility determinant in male subjects.

Melatonin as a potential tool against oxidative damage and apoptosis in ejaculated human spermatozoa.

It is assumed somatic cells can die in the apoptotic, the autophagic, or the necrotic way; however, the mechanisms of sperm death are not clear. Here, ejaculated human spermatozoa were evaluated for apoptosis and reactive oxygen species production in the absence or presence of melatonin, and we concluded that melatonin reverses sperm apoptosis due to its free radical scavenging actions.

Estudio del efecto Antidepresivo del extracto hidroalcohólico de hojas de Hypericum laricifolium (Chinchango) en ratones albinos / Study of the antidepressant effect of the hydroalcoholic extract of leaves of Hypericum laricifolium (Chinchango) in albino mice

El objetivo de esta investigación fue comprobar el efecto antidepresivo del extracto hidroalcohólico de las hojas de Hypericum laricifolium (Chinchango) en ratones albinos. Se empleó el modelo de natación forzada modificada (FST) donde se sometió a todos los animales a una sesión de habituación que consistió en sumergirlos en una piscina cilíndrica durante 15 minutos; posteriormente fueron tratados cada 12 horas de la siguiente manera: Grupo 1(n=13) vehículo 5 ml/Kg, Grupo 2 (n=13) Diazepan 10mg/Kg, Grupo 3 (n=13) Hypericum l (n=13) 1% 100mg/Kg y Grupo 4 (n=13) Hypericum l 10% 1000mg /Kg .Veinticuatro horas después se realizo la sesión de evaluación sometiéndolos a la experiencia anterior, durante 5 minutos. Se registró el tiempo de inmovilidad, swimming (natación) y climbing (escalado) para cada animal. Para la prueba de suspensión de la cola (TST) los animales fueron tratados cada 12 hrs de la siguiente manera Grupo 1(n=11) vehículo 5 ml/Kg Grupo 2 (n=11) Fluoxetina 10mg/Kg Grupo 3 (n=11) Hypericum l (n=11) 1% 100mg/Kg Grupo 4 Hypericum l 10% 1000mg /Kg. Veinticuatro horas más tarde los ratones fueron suspendidos individualmente por el tercio distal de la cola (prueba de suspensión de la cola) registrándose el tiempo de inmovilidad durante 6 minutos. En el modelo de FST los grupos Hypericum 1 % y 10% mostraron una reducción en el tiempo de inmovilidad en relación al grupo control 170 y 167 seg vs 231 seg respectivamente; el tiempo de swimiming para el grupo Hypericum al 10% en relación al grupo control fue 112 vs 48 seg respectivamente; no observándose modificaciones en el tiempo de climbing. En la prueba de TST los animales con Hypericum l al 10% y fluoxetina mostraron una significativa reducción del tiempo de inmovilidad en relación al grupo control 65 y 42 seg vs 108 segundos. En conclusión el extracto hidroalcoholico de las hojas de Hypericum laricifolium presentó efecto antidepresivo en ratones observándose un mayor efecto a la concentración del 10%.

Relationship between caspase activity and apoptotic markers in human sperm in response to hydrogen peroxide and progesterone.

Apoptosis plays an essential role in normal spermatogenesis, but deregulations of this biological process, which is closely associated with male infertility, have been found. Whereas calcium homeostasis is a key regulator of cell survival, sustained elevation of intracellular calcium plays a role in apoptosis. The aim of this research was to determine the role of two different calcium mobilizing agents, hydrogen peroxide (H(2)O(2)) and the physiological agonist progesterone, on the apoptosis process of human ejaculated spermatozoa. Translocation of membrane phosphatidylserine was examined with an annexin V binding assay, DNA damage was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling (TUNEL assay) and caspase-3 activity was assessed using a fluorometric assay. After incubation of spermatozoa for 1 h with either 10 microM H(2)O(2) or 20 microM of progesterone, there was a significant increase in both caspase-3 activity and the percentage of annexin V-positive cells. Similarly, the TUNEL results were significantly higher 1 h after incubation with either 10 microM H(2)O(2) or 20 microM of progesterone. In fact, progesterone-treated cells showed a three-fold increase (from 17.6 to 52.9%) of TUNEL-positive cells compared to untreated cells, while H(2)O(2)-treated cells exhibited a two-fold increase (from 17.6 to 37.9%). In sum, our results suggest that spermatozoa treated with calcium mobilizing agents, such as H(2)O(2) and progesterone, seem to undergo an apoptosis process that is dependent on caspase-3 activation.

Reduced levels of intracellular calcium releasing in spermatozoa from asthenozoospermic patients.

BACKGROUND: Asthenozoospermia is one of the most common findings present in infertile males characterized by reduced or absent sperm motility, but its aetiology remains unknown in most cases. In addition, calcium is one of the most important ions regulating sperm motility. In this study we have investigated the progesterone-evoked intracellular calcium signal in ejaculated spermatozoa from men with normospermia or asthenozoospermia. METHODS: Human ejaculates were obtained from healthy volunteers and asthenospermic men by masturbation after 4-5 days of abstinence. For determination of cytosolic free calcium concentration, spermatozoa were loaded with the fluorescent ratiometric calcium indicator Fura-2. RESULTS: Treatment of spermatozoa from normospermic men with 20 micromolar progesterone plus 1 micromolar thapsigargin in a calcium free medium induced a typical transient increase in cytosolic free calcium concentration due to calcium release from internal stores. Similar results were obtained when spermatozoa were stimulated with progesterone alone. Subsequent addition of calcium to the external medium evoked a sustained elevation in cytosolic free calcium concentration indicative of capacitative calcium entry. However, when progesterone plus thapsigargin were administered to spermatozoa from patients with asthenozoospermia, calcium signal and subsequent calcium entry was much smaller compared to normospermic patients. As expected, pretreatment of normospermic spermatozoa with both the anti-progesterone receptor c262 antibody and with progesterone receptor antagonist RU-38486 decreased the calcium release induced by progesterone. Treatment of spermatozoa with cytochalasin D or jasplakinolide decreased the calcium entry evoked by depletion of internal calcium stores in normospermic patients, whereas these treatments proved to be ineffective at modifying the calcium entry in patients with asthenozoospermia. CONCLUSION: Our results suggest that spermatozoa from asthenozoospermic patients present a reduced responsiveness to progesterone.

Caspase 3 activation in human spermatozoa in response to hydrogen peroxide and progesterone.

OBJECTIVE: To determine the role of calcium signaling on apoptosis evoked by the reactive oxygen species H2O2 and by the physiological agonist P in human ejaculated spermatozoa. DESIGN: Laboratory study. SETTING: Center for assisted human reproduction in a hospital in Spain. PATIENT(S): Forty-five healthy volunteers. INTERVENTION(S): Spermatozoa were treated with increasing concentrations of hydrogen peroxide (H2O2; 10 microM, 100 microM, and 1 mM) or with 20 microM of P for 5-120 minutes. MAIN OUTCOME MEASURE(S): Activation of caspase-3 and -9 as well as phosphatidylserine externalization were examined in human ejaculated spermatozoa by fluorescence methods. RESULT(S): Hydrogen peroxide and P induced activation of caspase-3 and -9. In addition, the effect of H2O2 and P was time dependent. Dimethyl-1,2-bis (aminophenoxy) ethane-N,N,N',N'-tetraacetic acid loading was able to inhibit H2O2- and P-induced caspase-3 activation and phosphatidylserine externalization. Pretreatment of spermatozoa with Ru360, to block the calcium uptake into mitochondria, also was able to decrease the activation of caspase-3 and phosphatidylserine exposure that was stimulated by either H2O2 or P. CONCLUSION(S): These findings suggest that H2O2- and P-induced mitochondrial apoptosis is dependent on calcium signaling.

Eritema nodoso: estudio prospectivo de su etiología en treinta y ocho pacientes / Erythema nodosum: prospective study of its etiology in 38 patients

Objetivo del trabajo: Hallar la etiología del EN en los pacientes de nuestra institución y determinar si existen caracteres clínicos o exámenes complementarios sugestivos de esas etiologías. Material y métodos: Entre abril de 1988 y abril de 1995 se estudiaron en forma prospectiva 38 pacientes con EN. Todos fueron examinados mediante una matriz de datos clínicos única y a todos se les solicitó los mismos estudios de laboratorio. En 34 pacientes se obtuvo una biopsia de piel. Se definieron previamente los criterios diagnósticos que permitieran establecer luego la etiología del EN (estreptocócico, medicamentoso, tuberculoso, etc). Resultados: La etiología pudo ser determinada en el 69 por ciento de los pacientes. En 18 casos EN estreptocócico, en 4 casos coincidió con medicamentos, en 3 casos fue atribuido al embarazo, en otros 3 a TBC (2 casos de adenitis TBC y uno asociado a tuberculide papulonecrótica) y en un caso se diagnosticó una enfermedad de Hodgkin. En una paciente, el EN se asoció a síndrome de Sweet y en otra a necrobiosis lipoídica