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An 83-year-old woman was admitted to our center because of heart failure. Transthoracic echocardiography revealed severe mitral annular calcification resulting in a double mitral valve lesion. After discussion by the heart team, transcatheter mitral valve replacement with Tendyne (Abbott Structural, Santa Clara, CA, USA) was performed. Despite having a predicted neo-left ventricular outflow tract (LVOT) above the cut-off value, the patient developed clinically significant LVOT obstruction (LVOTO) refractory to medical treatment. This situation is often treated before the intervention, and dealing with LVOTO afterward can be challenging. After taking the patient's anatomy into consideration, we decided to perform alcohol septal ablation. Applying a combined strategy of medical treatment and intervention led to success. In this case report, we discuss this event and the strategies available for preventing and managing the condition.

Esta contribución presenta un análisis del texto inédito recuperado “Encuentros con César Vallejo” del poeta y crítico Leopoldo de Luis. Los comentarios de de Luis ofrecen una síntesis que puede considerarse esencial en la poética hispánica surgida en la contemporaneidad y de la que Vallejo forma parte principal. La interpretación luisiana al integrar el historicismo crítico y sus tradiciones al comentario del texto resultan ejemplares y de ahí la necesidad de publicación pues une la crítica sobre Vallejo con las propias coordenadas de su poética en el contexto vivido por el propio Leopoldo de Luis.

In this study, we investigated the effects of eleven synthetic guanidines containing the 1,3-diphenylpropenone core on the viabilities of six human cancer cells. The most cytotoxic compound against human cancer cells of this series contains a N-tosyl group and a N-methylpiperazine moiety 6f. It was cytotoxic against leukemia cells (U-937, HL-60, MOLT-3, and NALM-6) with significant effects against Bcl-2-overexpressing U-937/Bcl-2 cells as well as the human melanoma SK-MEL-1 cell line. It exhibited low cytotoxicity against quiescent or proliferating human peripheral blood mononuclear cells. The IC50 value for the leukemia U-937 cells was 1.6 ± 0.6 µM, a similar value to that in the antineoplastic agent etoposide. The guanidine containing a N-phenyl substituent 6i was also as cytotoxic as the guanidine containing the N-tosyl substituent and the N-methylpiperazine group 6f against human U-937 leukemia cells and both synthetic guanidines were potent apoptotic inducers. Cell death was mediated by the activation of the initiator caspase-9 and the executioner caspase-3, and associated with the release of cytochrome c. These synthetic guanidines are potent cytotoxic compounds against several human leukemia cells and even the human melanoma cell line SK-MEL-1 and might be useful in the development of new strategies in the fight against cancer.

Resumen: Introducción: El recambio valvular aórtico con prótesis sin sutura Perceval S se asocia a un aumento en la tasa de bloqueo auriculoventricular postoperatorio que precisa implante de marcapasos definitivo, comparado con las bioprótesis convencionales. En nuestra serie hemos modificado la técnica de implante (mínimo baloneo

Inhibition of microtubule function using tubulin targeting agents has received growing attention in the last several decades. The indole scaffold has been recognized as an important scaffold in the design of novel compounds acting as antimitotic agents. Indole-based chalcones, in which one of the aryl rings was replaced by an indole, have been explored in the last few years for their anticancer potential in different cancer cell lines. Eighteen novel (3′,4′,5′-trimethoxyphenyl)-indolyl-propenone derivatives with general structure 9 were synthesized and evaluated for their antiproliferative activity against a panel of four different human cancer cell lines. The highest IC50 values were obtained against the human promyelocytic leukemia HL-60 cell line. This series of chalcone derivatives was characterized by the presence of a 2-alkoxycarbonyl indole ring as the second aryl system attached at the carbonyl of the 3-position of the 1-(3′,4′,5′-trimethoxyphenyl)-2-propen-1-one framework. The structure–activity relationship (SAR) of the indole-based chalcone derivatives was investigated by varying the position of the methoxy group, by the introduction of different substituents (hydrogen, methyl, ethyl or benzyl) at the N-1 position and by the activity differences between methoxycarbonyl and ethoxycarbonyl moieties at the 2-position of the indole nucleus. The antiproliferative activity data of the novel synthesized compounds revealed that generally N-substituted indole analogues exhibited considerably reduced potency as compared with their parent N-unsubstituted counterparts, demonstrating that the presence of a hydrogen on the indole nitrogen plays a decisive role in increasing antiproliferative activity. The results also revealed that the position of the methoxy group on the indole ring is a critical determinant of biological activity. Among the synthesized derivatives, compound 9e, containing the 2-methoxycarbonyl-6-methoxy-N-1H-indole moiety exhibited the highest antiproliferative activity, with IC50 values of 0.37, 0.16 and 0.17 μM against HeLa, HT29 and MCF-7 cancer cell lines, respectively, and with considerably lower activity against HL-60 cells (IC50: 18 μM). This derivative also displayed cytotoxic properties (IC50 values ∼1 μM) in the human myeloid leukemia U-937 cell line overexpressing human Bcl-2 (U-937/Bcl-2) via cell cycle progression arrest at the G2-M phase and induction of apoptosis. The results obtained also demonstrated that the antiproliferative activity of this molecule is related to inhibition of tubulin polymerisation. The presence of a methoxy group at the C5- or C6-position of the indole nucleus, as well as the absence of substituents at the N-1-indole position, contributed to the optimal activity of the indole-propenone-3′,4′,5′-trimethoxyphenyl scaffold.

The combination of two pharmacophores into a single molecule represents one of the methods that can be adopted for the synthesis of new anticancer molecules. To investigate the influence of the position of the pyridine nitrogen on biological activity, two different series of α-bromoacryloylamido indolyl pyridinyl propenones 3a–h and 4a–d were designed and synthesized by a pharmacophore hybridization approach and evaluated for their antiproliferative activity against a panel of six human cancer cell lines. These hybrid molecules were prepared to combine the α-bromoacryloyl moiety with two series of indole-inspired chalcone analogues, possessing an indole derivative and a 3- or 4-pyridine ring, respectively, linked on either side of 2-propen-1-one system. The structure-activity relationship was also investigated by the insertion of alkyl or benzyl moieties at the N-1 position of the indole nucleus. We found that most of the newly synthesized displayed high antiproliferative activity against U-937, MOLT-3, K-562, and NALM-6 leukaemia cell lines, with one-digit to double-digit nanomolar IC50 values. The antiproliferative activities of 3-pyridinyl derivatives 3f–h revealed that N-benzyl indole analogues generally exhibited lower activity compared to N-H or N-alkyl derivatives 3a–b and 3c–e, respectively. Moreover, cellular mechanism studies elucidated that compound 4a induced apoptosis along with a decrease of mitochondrial membrane potential and activated caspase-3 in a concentration-dependent manner.

The World Health Organization reported that approximately 324,000 new cases of melanoma skin cancer were diagnosed worldwide in 2020. The incidence of melanoma has been increasing over the past decades. Targeting apoptotic pathways is a potential therapeutic strategy in the transition to preclinical models and clinical trials. Some naturally occurring products and synthetic derivatives are apoptosis inducers and may represent a realistic option in the fight against the disease. Thus, chalcones have received considerable attention due to their potential cytotoxicity against cancer cells. We have previously reported a chalcone containing an indole and a pyridine heterocyclic rings and an α-bromoacryloylamido radical which displays potent antiproliferative activity against several tumor cell lines. In this study, we report that this chalcone is a potent apoptotic inducer for human melanoma cell lines SK-MEL-1 and MEL-HO. Cell death was associated with mitochondrial cytochrome c release and poly(ADP-ribose) polymerase cleavage and was prevented by a non-specific caspase inhibitor. Using SK-MEL-1 as a model, we found that the mechanism of cell death involves (i) the generation of reactive oxygen species, (ii) activation of the extrinsic and intrinsic apoptotic and mitogen-activated protein kinase pathways, (iii) upregulation of TRAIL, DR4 and DR5, (iv) downregulation of p21Cip1/WAF1 and, inhibition of the NF-κB pathway.

Ethanol has been shown to exhibit therapeutic properties as an ablative agent alone and in combination with thermal ablation. Ethanol may also increase sensitivity of cancer cells to certain physical and chemical antitumoral agents. The aim of our study was to assess the potential influence of nontoxic concentrations of ethanol on hyperthermia therapy, an antitumoral modality that is continuously growing and that can be combined with classical chemotherapy and radiotherapy to improve their efficiency. Human leukemia cells were included as a model in the study. The results indicated that ethanol augments the cytotoxicity of hyperthermia against U937 and HL60 cells. The therapeutic benefit of the hyperthermia/ethanol combination was associated with an increase in the percentage of apoptotic cells and activation of caspases-3, -8 and -9. Apoptosis triggered either by hyperthermia or hyperthermia/ethanol was almost completely abolished by a caspase-8 specific inhibitor, indicating that this caspase plays a main role in both conditions. The role of caspase-9 in hyperthermia treated cells acquired significance whether ethanol was present during hyperthermia since the alcohol enhanced Bid cleavage, translocation of Bax from cytosol to mitochondria, release of mitochondrial apoptogenic factors, and decreased of the levels of the anti-apoptotic factor myeloid cell leukemia-1 (Mcl-1). The enhancement effect of ethanol on hyperthermia-activated cell death was associated with a reduction in the expression of HSP70, a protein known to interfere in the activation of apoptosis at different stages. Collectively, our findings suggest that ethanol could be useful as an adjuvant in hyperthermia therapy for cancer.

Guaiane-type sesquiterpene lactones are naturally occurring compounds which have attracted attention due to their array of biological activities. In this study, chlorinated guaianolides 1–8, isolated from plants of the genus Centaurea, were evaluated against the human leukemia cell lines HL-60, U-937, a specific U-937 cell line that overexpresses the anti-apoptotic Bcl-2 protein and the human melanoma cell line SK-MEL-1. This established the relevant structure-growth inhibition relationships. Chlorohyssopifolins A (1), C (3) and D (4) and linichlorin A (6) were the most potent compounds in terms of inducing growth inhibition in the four cell lines. IC50 values were below 10 μM in all cases. Chlorohyssopifolins A (1) and D (4) and linichlorin A (6) were potent apoptotic inducers in human U-937 leukemia cells, as determined by fluorescent microscopy and flow cytometry, and their mechanism of action was associated with cytochrome c release, caspase activation and poly(ADP-ribose)polymerase cleavage. Overall this study shows that guaianolides induce cytotoxicity against human tumor cells and provides important insights into the cell death pathways that are involved.

Introducción y objetivos: La insuficiencia mitral (IM) isquémica crónica es una patología frecuente y compleja, consecuencia del remodelado ventricular y anular mitral asimétrico que acontece tras el infarto de miocardio. El anillo protésico Carpentier-McCarthy-Adams IMR ETlogix® (Edwards Lifesciences Corporation) actúa específicamente sobre esta deformación geométrica. Analizamos nuestros resultados tras 10 años realizando esta técnica. Métodos: Noventa pacientes con IM isquémica crónica grado ≥ 2 fueron sometidos consecutivamente a anuloplastia mitral con anillo IMR ETlogix® desde 2005 hasta 2015; 75 (83,3%) presentaban clase funcional NYHA III-IV. Sesenta y seis (73,3%) fueron intervenidos con carácter urgente. En 73 (81,1%) asociamos otro procedimiento cardíaco. Obtuvimos seguimiento clínico y ecocardiográfico periódico de todos los pacientes que superaron la cirugía. Resultados: Mediana de seguimiento 62 meses (12-129). Mortalidad hospitalaria de 1 paciente (1,1%); 16 pacientes fallecidos en el seguimiento (7 de causa cardíaca). El ecocardiograma de control tardío objetivó recidiva significativa (IM grado ≥ 2) en 6 pacientes (2 de ellos IM grado > 2), con una reintervención por dehiscencia anular. No hubo incremento significativo en el gradiente medio transmitral. El análisis univariado objetivó la altura de tenting preoperatoria como mejor predictor de recidiva de la IM en nuestra serie, con un punto de corte en 10,65 mm (sensibilidad 100%, especificidad 93%, área bajo la curva ROC 0,97). Conclusiones: La anuloplastia con anillo IMR ETlogix® es una técnica segura y eficaz para corregir la IM isquémica crónica, fundamentalmente en pacientes con una altura de tenting preoperatoria inferior a 10,65 mm.

Objetivo: Determinar la incidencia de deterioro valvular estructural (DVE) entre todos los modelos de bioprótesis aórtica Mitroflow (A12/LX/DL), así como definir los factores de riesgo implicados y el posible papel protector del tratamiento anticalcificación phospholipid reduction treatment (PRT) del modelo DL. Métodos: Estudio retrospectivo de 1.023 pacientes consecutivos operados de recambio valvular aórtico con bioprótesis Mitroflow entre 2001 y 2014. Resultados: El seguimiento medio fue de 5,4 ± 3,1 años. La incidencia acumulada global de DVE fue 0,48% a un año, 2,1% a 5 años y 6,8% a 10 años. El grupo PRT mostró menor incidencia acumulada de DVE (0,2% vs. 1,2% a 4 años) (p = 0,04). El análisis de regresión de riesgos competitivos confirmó: edad < 70 años (HR = 2,98 [1,5-5,89], p = 0,002), tamaño valvular de 19 mm (HR = 4,7 [2,29-9,64], p 30 mmHg en postoperatorio precoz (HR = 10,3 [5,3-19,9], p

BCR-ABL1-STAT5 is an oncogenic signaling pathway in human chronic myelogenous leukemia (CML) and it represents a valid target for anti-CML drug design. Resistance to direct BCR-ABL1 inhibitors is a common clinical issue, so STAT5 inhibition has become an interesting alternative target. In this study, the effects of NPQ-C6, a novel naphtoquinone-coumarin conjugate, were evaluated on human CML-derived K562 cells. Live-Cell Imaging analysis revealed that NPQ-C6 inhibited 2D (IC50AUC = 1.4 ± 0.6 μM) growth of CML cells. NPQ-C6 increased sub-G1 and reduced G0/G1 cell cycle phases in a dose- and time-dependent manner. This effect on cell cycle was related to increased levels of apoptotic nuclei, cleavage of caspase-3, -9, and PARP and annexin V-positive cells. NPQ-C6 increased γH2AX, a double-strand DNA break marker. NPQ-C6 showed a wide range of modulatory effects on cell signaling through an early increased phosphorylation of JNK, P38-MAPK and AKT, and decreased phosphorylation of ERK1/2, BCR-ABL1, and STAT5. NPQ-C6 inhibited expression of c-MYC and PYM-1, two target gene products of BCR-ABL1/STAT5 signaling pathway. Cytokine-induced activation of STAT5/STAT3-dependent transcriptional and DNA binding activities were also inhibited by NPQ-C6. Notably, NPQ-C6 maintained its activity on BCR-ABL1/STAT5/c-MYC/PIM-1 oncogenic pathway in imatinib-resistant cells. Molecular modeling suggested BCR-ABL1 and JAK2 proteins as NPQ-C6 targets. In summary, our data show a novel multikinase modulator that might be therapeutically effective in BCR-ABL1-STAT5-related malignancies.

Induction of apoptosis is a common chemotherapeutic mechanism to kill cancer cells The thiazole system has been reported over the past decades as a building block for the preparation of anticancer agents. A novel series of 2-arylalkylamino-4-amino-5-(3′,4′,5′-trimethoxybenzoyl)-thiazole derivatives designed as dual inhibitors of tubulin and cyclin-dependent kinases (CDKs) were synthesized and evaluated for their antiproliferative activity in vitro against two cancer cell lines and, for selected highly active compounds, for interactions with tubulin and cyclin-dependent kinases and for cell cycle and apoptosis effects. Structure-activity relationships were elucidated for various substituents at the 2-position of the thiazole skeleton. Among the synthesized compounds, the most active analogues were found to be the p-chlorobenzylamino derivative 8e as well as the p-chloro and p-methoxyphenethylamino analogues 8f and 8k, respectively, which inhibited the growth of U-937 and SK-MEL-1 cancer cell lines with IC50 values ranging from 5.7 to 12.2 μM. On U-937 cells, the tested compounds 8f and 8k induced apoptosis in a time and concentration dependent manner. These two latter molecules did not affect tubulin polymerization (IC50 > 20 μM) nor CDK activity at a single concentration of 10 μM, suggesting alternative targets than tubulin and CDK for the compounds.

Spiciformin (1) is a sesquiterpene lactone with a germacrane skeleton that is found in two Tanacetum species endemic to the Canary Islands. In this study, the cytotoxicities of 1 and its acetyl derivative (2) were evaluated against human tumor cells. These sesquiterpene lactones were cytotoxic against human acute myeloid leukemia (U-937 and HL-60) cells, even in cells over-expressing the pro-survival protein Bcl-2, but melanoma (SK-MEL-1) and human mononuclear cells isolated from blood of healthy donors were more resistant. Both compounds are apoptotic inducers in human leukemia U-937 cells. Cell death was mediated by the processing and activation of initiator and effector caspases and the cleavage of poly(ADP-ribose) polymerase, and it was blocked by a broad-spectrum caspase inhibitor and (in the case of sesquiterpene lactone 2) by the selective caspase-3/7, -8, and -9 inhibitors. In addition, certainly in the case of compound 2, this was found to be associated with a decrease in mitochondrial membrane potential, downregulation of the anti-apoptotic protein Bcl-2, activation of the mitogen-activated protein kinases signaling pathway, and generation of reactive oxygen species. It will, therefore, be relevant to continue characterization of this class of compounds.

Melatonin is present in all living organisms where it displays a diversity of physiological functions. Attenuation of melanogenesis by melatonin has been reported in some mammals and also in rodent melanoma cells. However, melatonin may also stimulate melanogenesis in human melanoma cells through mechanisms that have not yet been revealed. Using the human melanoma cells SK-MEL-1 as a model, an increase in both tyrosinase activity and melanin was already observed at 24 h after melatonin treatment with maximal levels of both being detected at 72 h. This effect was associated with the induction in the expression of the enzymes involved in the synthesis of melanin. In this scenario, glycogen synthase kinase-3β seems to play a significant function since melatonin decreased its phosphorylation and preincubation with specific inhibitors of this protein kinase (lithium or BIO) reduced the expression and activity of tyrosinase. Blocking of PI3K/AKT pathway stimulated melanogenesis and the effect was suppressed by the inhibitors of glycogen synthase kinase-3β. Although melatonin is a recognized antioxidant, we found that it stimulates reactive oxygen species generation in SK-MEL-1 cells. These chemical species seem to be an important signal in activating the melanogenic process since the antioxidants N-acetyl-l-cysteine and glutathione decreased both the level and activity of tyrosinase stimulated by melatonin. Our results support the view that regulation of melanogenesis involves a cross-talk between several signaling pathways.

Objetivos: Analizar la morfología del arco aórtico en pacientes sometidos a cirugía híbrida por patología de arco y aorta torácica descendente, así como evaluar los resultados a corto y a medio plazo. Pacientes y métodos: Catorce pacientes consecutivos (78,6% varones, con edad media de 61,9 ± 10,1 años y euroSCORE logístico medio 19,2 ± 9,6%) operados mediante cirugía híbrida (derivación carótido-subclavia izquierda, 7 casos; translocación de 2 troncos, 2 casos; translocación de 3 troncos, 5 casos) fueron incluidos en el estudio. Se analizaron los diámetros aórticos, la longitud de las zonas de anclaje, la distancia entre troncos supraaórticos, la angulación y el radio de curvatura del arco. Resultados: La longitud media de la zona de anclaje proximal aumentó de 5,9 ± 5,3 a 36,3 ± 9,6 mm tras cirugía de troncos supraaórticos. El radio de curvatura medio del arco fue de 48,7 ± 19,9 mm con angulación media de 84,6 ± 29,1°. Cuatro pacientes presentaron un radio de curvatura 2,5 cm para evitar defectos de aposición en la curvatura menor del arco y endofugas tipo ia.

Phytochemical research of two Tolpis species, T. proustii and T. lagopoda, led to the isolation of three new compounds: 30-chloro-3β-acetoxy-22α-hydroxyl-20(21)-taraxastene (1), 3β,22α-diacetoxy-30-ethoxy-20(21)-taraxastene (2) and 3β,28-dihydroxy-11α-hydroperoxy-12-ursene (3). The structures of the new compounds were elucidated by means of extensive IR, NMR, and MS data and by comparison of data reported in the literature. The in vitro antioxidant activities of the extracts were assessed by the DPPH and ABTS scavenging methods. The cytotoxicity of several known compounds and its derivatives was also assessed against human myeloid leukemia K-562 and K-562/ADR cell lines.

Introducción: la exigencia de demostración de la intercambiabilidad de medicamentos genéricos en relación con los innovadores comenzó en el mundo desarrollado en la década de 1970. Objetivo: en el presente artículo se hace una breve reseña histórica señalando los medicamentos con los cuales y por primera vez se constataron problemas de bioequivalencia. Resultados: se señala que la implementación de la intercambiabilidad en América Latina comienza a principios de la primera década de este siglo, impulsado por un grupo de trabajo de la Organización Panamericana de la Salud (OPS), y que Uruguay comenzó a legislar en la materia en enero de 2007. Se definen los conceptos de bioequivalencia y de intercambiabilidad de medicamentos y se aclara cuáles son los medicamentos que deberían cumplir con esta exigencia en nuestro país. Se examinan los criterios para diseñar un listado de prioridades para exigir la bioequivalencia y se hace una revisión del marco regulatorio que nuestro país se ha dado desde el año 2007. Se hace referencia a diseños específicos de estos estudios cuyo objetivo es evaluar la interacción de las nuevas formulaciones "retard" con la comida o minimizar el efecto de la variabilidad intraindividual sobre la potencia estadística de los estudios. Conclusiones: se comentan algunos detalles mejorables de la normativa y el impacto de los estudios de bioequivalencia sobre los hábitos de prescripción, el mercado farmacéutico en Uruguay y la accesibilidad a medicamentos eficaces y seguros.

The idea about picaresque novel got a place inside the most misty and wandering of the compared literature. with the purpose of expanding on that strict field, the concept has been redefine in a sense of «tradición picaresca», or even in terms used by Guillén or Blackburn, of a «mito picaresco». Then, in a dialectic way, and through the hermeutic circle, the genre is continuously enriched and modified with new novels. El difunto Matías Pascal, of Luigi Pirandello, shows iconic elements that refers to the original picaresque novel and satisfies the higher criteria of that enlarge critic category. The main character of the novel, from the poetic of the picaresque character and in a evolved key, after the romantic heroes interval mostly homogeneous, rediscover the opposite prototype of the 176h century critic novel, of origin and picaresque background.

Eupatorin is a naturally occurring flavone that inhibits cell proliferation in human tumor cells. Here we demonstrate that eupatorin arrests cells at the G2-M phase of the cell cycle and induces apoptotic cell death involving activation of multiple caspases, mitochondrial release of cytochrome c and poly(ADP-ribose) polymerase cleavage in human leukemia cells. This flavonoid induced the phosphorylation of members of the mitogen-activated protein kinases and cell death was attenuated by inhibition of c-jun N-terminal kinases/stress activated protein kinases. Eupatorin-induced cell death is mediated by both the extrinsic and the intrinsic apoptotic pathways and through a mechanism dependent on reactive oxygen species generation.

Sin resumen.

Las reacciones cutáneas son las reacciones adversas medicamentosas más frecuentes, ocurriendo en 2% de todos los tratamientos. El objetivo de este trabajo es realizar una revisión de los medicamentos que con mayor frecuencia causan el síndrome de Stevens-Johnson, la necrólisis epidérmica tóxica y señalar sus manifestaciones clínicas basados en la literatura y en los reportes del sistema nacional de farmacovigilancia. Especialmente nos interesa señalar estos síndromes como un problema relacionado a los medicamentos, ya que algunos fármacos, muchos de ellos de uso prevalente, son el agente etiológico en la mayoría de los casos. La suspensión de aquellos no destinados a sostener una función vital es prioritaria ante la sospecha de una reacción cutánea severa. Existen síntomas y signos que permiten al médico identificar los casos potencialmente graves. Los compuestos asociados con este tipo de reacciones sólo pueden ser identificados si los clínicos sospechan que existe una relación causa-efecto y posteriormente la informan. Es difícil conocer todo acerca de todos los medicamentos que prescribimos. Podemos acercarnos a esa meta si seleccionamos unos pocos para nuestra práctica clínica habitual.

Jacques-Alain MILLER es psicoanalista, editor -uno de cuyos principales cometidos consiste en establecer los textos y la publicación de los Seminarios de Jacques LACAN, tal como le encargó el propio maestro escritor, prestigioso conferenciante y profesor especializado en los fundamentos del psicoanálisis. En la actualidad dirige el Departamento de Psicoanálisis de la Universidad de París VIII. Es miembro del Consejo de la Escuela de la Causa Freudiana, editor de las publicaciones del Campo Freudiano y director de la revista Ornicar, una de las más importantes publicaciones psicoanalíticas en el panorama internacional. Está casado con Judith MILLER -hija de LACAN-, presidenta de la Fundación del Campo Freudiano, con la que tiene dos hijos. Ha visitado España en numerosas ocasiones, pronunciando conferencias, dictando seminarios e impulsando la articulación de grupos de estudio psicoanalíticos en diversas ciudades. Es asesor editorial de la revista «El Analiticón», publicación del Campo Freudiano en España.