Papiledema como posible signo guía en el diagnóstico del síndrome periódico asociado a la criopirina: a propósito de un caso / Papilledema as a possible key sign for diagnosis of cryopyrin-associated periodic syndromes (CAPS): A case report

El síndrome periódico asociado a la criopirina es una enfermedad rara y probablemente infradiagnosticada. Se presenta con manifestaciones sistémicas, entre ellas oftalmológicas, muy diversas, por lo que su diagnóstico supone un reto para el clínico. Presentamos el caso de una niña de 4 años en la que la identificación de papiledema en el examen oftalmológico constituyó el signo guía para el diagnóstico de síndrome periódico asociado a la criopirina. Pretendemos así concienciar sobre esta enfermedad de graves implicaciones y cuyo diagnóstico precoz resulta esencial para los afectados, para que sea tenido en cuenta con mayor frecuencia como diagnóstico diferencial (AU)

Cryopyrin-associated periodic syndrome is a rare and probably underdiagnosed disease. It presents with various systemic manifestations, including ophthalmological, making its diagnosis a challenge for the clinician. We present the case of a 4-year-old girl for which the identification of papilledema in the ophthalmological examination was the key sign for the diagnosis of cryopyrin-associated periodic syndrome. Our aim is to raise awareness of this syndrome with serious implications for affected patients, so that it is taken into account more frequently as a differential diagnosis, allowing an early diagnosis (AU)

Papilledema as a possible key sign for diagnosis of cryopyrin-associated periodic syndromes (CAPS): A case report.

Cryopyrin-associated periodic syndrome is a rare and probably underdiagnosed disease. It presents with various systemic manifestations, including ophthalmological, making its diagnosis a challenge for the clinician. We present the case of a 4-year-old girl for which the identification of papilledema in the ophthalmological examination was the key sign for the diagnosis of cryopyrin-associated periodic syndrome. Our aim is to raise awareness of this syndrome with serious implications for affected patients, so that it is taken into account more frequently as a differential diagnosis, allowing an early diagnosis.

ΔK=0 M1 Excitation Strength of the Well-Deformed Nucleus

The size of a ΔK=0 M1 excitation strength has been determined for the first time in a predominantly axially deformed even-even nucleus. It has been obtained from the observation of a rare K-mixing situation between two close-lying J^{π}=1^{+} states of the nucleus ^{164}Dy with components characterized by intrinsic projection quantum numbers K=0 and K=1. Nuclear resonance fluorescence induced by quasimonochromatic linearly polarized γ-ray beams provided evidence for K mixing of the 1^{+} states at 3159.1(3) and 3173.6(3) keV in excitation energy from their γ-decay branching ratios into the ground-state band. The ΔK=0 transition strength of B(M1;0_{1}^{+}→1_{K=0}^{+})=0.008(1)µ_{N}^{2} was inferred from a mixing analysis of their M1 transition rates into the ground-state band. It is in agreement with predictions from the quasiparticle phonon nuclear model. This determination represents first experimental information on the M1 excitation strength of a nuclear quantum state with a negative R-symmetry quantum number.

Efectos de la curva de aprendizaje en los resultados de la duodenopancreatectomía cefálica en un hospital de nivel II / Effects of the learning curve on the results of cephalic pancreaticoduodenectomy in a level II hospital

Resumen Introducción: La duodeno pancreatectomía cefálica es una operación compleja cuyos resultados a corto plazo son multifactoriales. Objetivo: Evaluar el impacto de la curva de aprendizaje en los resultados a corto plazo de la duodenopancreatectomía cefálica en un hospital de nivel II. Materiales y Método: Se analizaron los datos obtenidos a partir de una base de datos mantenida prospectivamente desde 2005. Se definieron dos periodos de tiempo: de 2005 a 2011 y de 2012 a 2017. Se compararon la morbilidad, mortalidad y estancia postoperatoria de ambos períodos. Resultados: Durante el período de tiempo estudiado se hicieron 126 duodenopancreatectomías cefálicas, 61 durante la primera etapa y 65 durante la segunda. La tasa de transfusión intraoperatoria se redujo de 33% a 15% (p = 0,011). La tasa de transfusión postoperatoria se redujo de 39 a 23% (p = 0,021). No hubo diferencias significativas con respecto a la incidencia global de complicaciones postoperatorias (59% y 52,3%). La incidencia de abscesos intraabdominales fue significativamente menor en el segundo período (18% y 4,6%, respectivamente; p = 0,038). La tasa de reintervenciones se redujo significativamente, de 22% a 9% (p = 0,049). También se redujo significativamente la tasa de mortalidad, de 6,56% a 0% (p = 0,032). La estancia media postoperatoria disminuyó significativamente en el segundo período, pasando de 19,6 a 15,8 días (p = 0,001), con una mayor proporción de pacientes dados de alta en los 8 primeros días de postoperatorio (11,5% y 38,5%, respectivamente; p = 0,001). Conclusión: La curva de aprendizaje es un factor que permite mejorar los resultados de la duodenopancreatectomía cefálica, en un hospital de nivel II, hasta alcanzar valores similares a los de un hospital de nivel III.

Introduction: The duodenum pancreatectomy cephalic is a complex operation whose short-term results are multifactorial. Aim: To assess the impact of the learning curve on the short-term outcomes of cephalic duodenopancreatectomy at a level II hospital. Materials Method: We analyze the data obtained from a database maintained prospectively since 2005. Two time periods were defined: from 2005 to 2011 and from 2012 to 2017. The morbidity, mortality and postoperative stay of both periods were compared. Results: 126 cephalic duodenopancreatectomies were performed, 61 during the first period and 65 during the second. The intraoperative transfusion rate was reduced from 33% to 15% (p = 0.011). The postoperative transfusion rate was reduced from 39 to 23% (p = 0.021). There were no significant differences with respect to the overall incidence of postoperative complications (59% and 52.3%, respectively). However, the incidence of intra-abdominal abscesses was significantly lower in the second period (18% and 4.6%, respectively, p = 0.038). The rate of reoperations was significantly reduced, from 22% to 9% (p = 0.049). The mortality rate was also significantly reduced, from 6.56% to 0% (p = 0.032). The mean postoperative stay decreased significantly in the second period, from 19.6 to 15.8 days (p = 0.001), with a higher proportion of patients discharged in the first 8 postoperative days (11.5% and 38.5%, respectively, p = 0.001). Conclusion: The learning curve is a factor allows improving the results of cephalic pancreaticoduodenectomy, in a level II hospital, until reaching values similar to those of a level III hospital.

Current management of breakthrough cancer pain according to physicians from pain units in Spain.

PURPOSE: Current evidence suggests the need to improve the management of breakthrough cancer pain (BTcP). For this reason, we aimed to assess the opinion of a panel of experts composed exclusively of physicians from pain units, who play a major role in BTcP diagnosis and treatment, regarding the key aspects of BTcP management. METHODS: An ad hoc questionnaire was developed to collect real-world data on the management of BTcP. The questionnaire had 5 parts: (a) organizational aspects of pain units (n = 12), (b) definition and diagnosis (n = 3), (c) screening (n = 3), (d) treatment (n = 8), and (e) follow-up (n = 7). RESULTS: A total of 89 pain-unit physicians from 13 different Spanish regions were polled. Most of them agreed on the traditional definition of BTcP (78.9%) and the key features of BTcP (92.1%). However, only 30.3% of participants used the Davies' algorithm for BTcP diagnosis. Respondents preferred to prescribe rapid-onset opioids [mean 77.0% (SD 26.7%)], and most recommended transmucosal fentanyl formulations as the first option for BTcP. There was also considerable agreement (77.5%) on the need for early follow-up (48-72 h) after treatment initiation. Finally, 65.2% of participants believed that more than 10% of their patients underused rapid-onset opioids. CONCLUSIONS: There was broad agreement among pain experts on many important areas of BTcP management, except for the diagnostic method. Pain-unit physicians suggest that rapid-onset opioids may be underused by BTcP patients in Spain, an important issue that need to be evaluated in future studies.

Molecular Evidence of Genome Editing in a Mouse Model of Immunodeficiency.

Genome editing is the introduction of directed modifications in the genome, a process boosted to therapeutic levels by designer nucleases. Building on the experience of ex vivo gene therapy for severe combined immunodeficiencies, it is likely that genome editing of haematopoietic stem/progenitor cells (HSPC) for correction of inherited blood diseases will be an early clinical application. We show molecular evidence of gene correction in a mouse model of primary immunodeficiency. In vitro experiments in DNA-dependent protein kinase catalytic subunit severe combined immunodeficiency (Prkdc scid) fibroblasts using designed zinc finger nucleases (ZFN) and a repair template demonstrated molecular and functional correction of the defect. Following transplantation of ex vivo gene-edited Prkdc scid HSPC, some of the recipient animals carried the expected genomic signature of ZFN-driven gene correction. In some primary and secondary transplant recipients we detected double-positive CD4/CD8 T-cells in thymus and single-positive T-cells in blood, but no other evidence of immune reconstitution. However, the leakiness of this model is a confounding factor for the interpretation of the possible T-cell reconstitution. Our results provide support for the feasibility of rescuing inherited blood disease by ex vivo genome editing followed by transplantation, and highlight some of the challenges.

Lentiviral-Mediated Gene Therapy in Fanconi Anemia-A Mice Reveals Long-Term Engraftment and Continuous Turnover of Corrected HSCs.

Fanconi anemia is a DNA repair-deficiency syndrome mainly characterized by cancer predisposition and bone marrow failure. Trying to restore the hematopoietic function in these patients, lentiviral vector-mediated gene therapy trials have recently been proposed. However, because no insertional oncogenesis studies have been conducted so far in DNA repair-deficiency syndromes such as Fanconi anemia, we have carried out a genome-wide screening of lentiviral insertion sites after the gene correction of Fanca(-/-) hematopoietic stem cells (HSCs), using LAM-PCR and 454-pyrosequencing. Our studies first demonstrated that transduction of Fanca(-/-) HSCs with a lentiviral vector designed for clinical application efficiently corrects the phenotype of Fanconi anemia repopulating cells without any sign of toxicity. The identification of more than 6,500 insertion sites in primary and secondary recipients showed a polyclonal pattern of reconstitution, as well as a continuous turnover of corrected Fanca(-/-) HSC clones, without evidences of selection towards specific common integration sites. Taken together our data show, for the first time in a DNA repair-deficiency syndrome, that lentiviral vector-mediated gene therapy efficiently corrects the phenotype of affected HSCs and promotes a healthy pattern of clonal turnover in vivo. These studies will have a particular impact in the development of new gene therapy trials in patients affected by DNA repair syndromes, particularly in Fanconi anemia.

Tratamiento del dolor irruptivo con fentanilo sublingual en pacientes con úlceras cutáneas crónicas / Breakthrough pain treatment with sublingual fentanyl in patients with chronic cutaneous ulcers

Objetivo. El presente estudio pretende establecer la eficacia y tolerabilidad de los opioides en el tratamiento del dolor en pacientes con úlceras cutáneas crónicas y dolor irruptivo incidental. Material y método. Estudio abierto, multicéntrico, prospectivo, no controlado, realizado en unidades del dolor y de úlceras de 5 hospitales de la Comunidad Valenciana. El criterio de inclusión fue dolor basal mayor o igual a 4 según la escala visual analógica o dolor irruptivo mayor o igual a 4 durante la cura. Los criterios de exclusión fueron alteraciones cognitivas, intolerancia a opioides y rechazo del paciente a dar el consentimiento. El protocolo estableció 5 momentos de evaluación: basal (primera visita), 15 días, un mes, 2 y 3 meses. La variable principal del estudio fue el dolor medido con la escala visual analógica en reposo, en movimiento y durante la cura. Se administraron opioides para el dolor basal y se administró fentanilo sublingual para el dolor irruptivo. Resultados. Treinta y dos pacientes (86,5%) completaron el estudio. El dolor basal experimentó una reducción media de 3,6 (DE 2,3) puntos en la escala visual analógica, el dolor en movimiento disminuyó 3,9 (DE 2,5), y el dolor durante la cura disminuyó 4,5 (DE 2,8), siendo en todos estadísticamente significativa (p < 0,001) desde el primer control. Catorce pacientes (43,8%) presentaron náuseas, 7 (21,9%), somnolencia y estreñimiento, 5 (15,6%), prurito, y uno (3,1%), vómitos. Conclusiones. Los resultados de nuestro estudio evidencian que el tratamiento con opioides en pacientes con úlceras cutáneas crónicas proporciona un alivio efectivo del dolor, tanto basalmente como durante la cura, con escasos efectos adversos (AU)

Objective. The aim of the study was to assess the efficacy and safety of opioids in the management of pain in those patients with chronic cutaneous ulcers and breakthrough/incidental pain. Material and method. An open-label, multicentre, prospective, uncontrolled study was conducted in the pain and ulcer units of 5 hospitals across the Comunidad Valenciana. Eligibility criteria were baseline pain 4 in the visual analogue scale or breakthrough procedural pain 4. Exclusion criteria were cognitive impairment, opioid intolerance, or patient refusal to provide informed consent. The protocol scheduled 5 controls: baseline (enrolment), 15 days, one month, 2 months, and 3 months. The main outcome measure of the study was the visual analogue scale score during rest, movement and procedures. Opioids were administered for release of the baseline pain, and sublingual fentanyl for breakthrough pain. Results. A total of 32 patients (86.5%) completed the study. Baseline pain achieved a mean improvement of 3.6 visual analogue scale points (SD 2.3), movement pain improved by 3.9 points (SD 2.5) and procedural pain improved by 4.5 points (SD 2.8), and the mean pain intensity improvement was statistically significant from the first control and at all controls thereafter (P < .001). Nausea was reported by 14 patients (43.8%), drowsiness and constipation by 7 (21.9%), itching by 5 (15.6%), and one (3.1%) reported vomiting. Conclusions. Structured assessment of pain is a key concept in the management of patient with chronic cutaneous ulcers. The results of this study suggest that opioid therapy provides clinically significant pain relief with few adverse effects (AU)

[Breakthrough pain treatment with sublingual fentanyl in patients with chronic cutaneous ulcers]. / Tratamiento del dolor irruptivo con fentanilo sublingual en pacientes con úlceras cutáneas crónicas.

OBJECTIVE: The aim of the study was to assess the efficacy and safety of opioids in the management of pain in those patients with chronic cutaneous ulcers and breakthrough/incidental pain. MATERIAL AND METHOD: An open-label, multicentre, prospective, uncontrolled study was conducted in the pain and ulcer units of 5 hospitals across the Comunidad Valenciana. Eligibility criteria were baseline pain 4 in the visual analogue scale or breakthrough procedural pain 4. Exclusion criteria were cognitive impairment, opioid intolerance, or patient refusal to provide informed consent. The protocol scheduled 5 controls: baseline (enrolment), 15 days, one month, 2 months, and 3 months. The main outcome measure of the study was the visual analogue scale score during rest, movement and procedures. Opioids were administered for release of the baseline pain, and sublingual fentanyl for breakthrough pain. RESULTS: A total of 32 patients (86.5%) completed the study. Baseline pain achieved a mean improvement of 3.6 visual analogue scale points (SD 2.3), movement pain improved by 3.9 points (SD 2.5) and procedural pain improved by 4.5 points (SD 2.8), and the mean pain intensity improvement was statistically significant from the first control and at all controls thereafter (P<.001). Nausea was reported by 14 patients (43.8%), drowsiness and constipation by 7 (21.9%), itching by 5 (15.6%), and one (3.1%) reported vomiting. CONCLUSIONS: Structured assessment of pain is a key concept in the management of patient with chronic cutaneous ulcers. The results of this study suggest that opioid therapy provides clinically significant pain relief with few adverse effects.

Generation of iPSCs from genetically corrected Brca2 hypomorphic cells: implications in cell reprogramming and stem cell therapy.

Fanconi anemia (FA) is a complex genetic disease associated with a defective DNA repair pathway known as the FA pathway. In contrast to many other FA proteins, BRCA2 participates downstream in this pathway and has a critical role in homology-directed recombination (HDR). In our current studies, we have observed an extremely low reprogramming efficiency in cells with a hypomorphic mutation in Brca2 (Brca2(Δ) (27/) (Δ27)), that was associated with increased apoptosis and defective generation of nuclear RAD51 foci during the reprogramming process. Gene complementation facilitated the generation of Brca2(Δ) (27/) (Δ27) induced pluripotent stem cells (iPSCs) with a disease-free FA phenotype. Karyotype analyses and comparative genome hybridization arrays of complemented Brca2(Δ) (27/) (Δ27) iPSCs showed, however, the presence of different genetic alterations in these cells, most of which were not evident in their parental Brca2(Δ) (27/) (Δ27) mouse embryonic fibroblasts. Gene-corrected Brca2(Δ) (27/) (Δ27) iPSCs could be differentiated in vitro toward the hematopoietic lineage, although with a more limited efficacy than WT iPSCs or mouse embryonic stem cells, and did not engraft in irradiated Brca2(Δ) (27/) (Δ27) recipients. Our results are consistent with previous studies proposing that HDR is critical for cell reprogramming and demonstrate that reprogramming defects characteristic of Brca2 mutant cells can be efficiently overcome by gene complementation. Finally, based on analysis of the phenotype, genetic stability, and hematopoietic differentiation potential of gene-corrected Brca2(Δ) (27/) (Δ) (27) iPSCs, achievements and limitations in the application of current reprogramming approaches in hematopoietic stem cell therapy are also discussed.

Brief report: impaired cell reprogramming in nonhomologous end joining deficient cells.

Although there is an increasing interest in defining the role of DNA damage response mechanisms in cell reprogramming, the relevance of proteins participating in nonhomologous end joining (NHEJ), a major mechanism of DNA double-strand breaks repair, in this process remains to be investigated. Herein, we present data related to the reprogramming of primary mouse embryonic fibroblasts (MEF) from severe combined immunodeficient (Scid) mice defective in DNA-PKcs, a key protein for NHEJ. Reduced numbers of induced pluripotent stem cell (iPSC) colonies were generated from Scid cells using reprogramming lentiviral vectors (LV), being the reprogramming efficiency fourfold to sevenfold lower than that observed in wt cells. Moreover, these Scid iPSC-like clones were prematurely lost or differentiated spontaneously. While the Scid mutation neither reduce the proliferation rate nor the transduction efficacy of fibroblasts transduced with reprogramming LV, both the expression of SA-ß-Gal and of P16/INK(4a) senescence markers were highly increased in Scid versus wt MEFs during the reprogramming process, accounting for the reduced reprogramming efficacy of Scid MEFs. The use of improved Sleeping Beauty transposon/transposase systems allowed us, however, to isolate DNA-PKcs-deficient iPSCs which preserved their parental genotype and hypersensitivity to ionizing radiation. This new disease-specific iPSC model would be useful to understand the physiological consequences of the DNA-PKcs mutation during development and would help to improve current cell and gene therapy strategies for the disease.

Collective structure in 94Zr and subshell effects in shape coexistence.

Based on results from a measurement of weak decay branches observed following the ß- decay of 94Y and on lifetime data from a study of 94Zr by inelastic neutron scattering, collective structure is deduced in the closed-subshell nucleus 94Zr. These results establish shape coexistence in 94Zr. The role of subshells for nuclear collectivity is suggested to be important.

Usefulness of tenderness to characterise fibromyalgia severity in women.

OBJECTIVES: To investigate the usefulness of tenderness (tender points count (TPC) and algometer score) to characterise fibromyalgia (FM) severity and symptomatology in women. METHODS: The study sample comprised 174 women aged 51±7 years. We ossesse tenderness using pressure algometry; quality of life by means of the Short-Form 36 Health Survey (SF-36) and the Hospital Anxiety and Depression Scale (HADS). We used the FM impact questionnaire (FIQ) to assess FM severity and symptomatology. Patients were categorised according to three FIQ-derived categories: FIQ<70 vs. ≥70; FIQ<59 vs. ≥59; and FM-type I and II. RESULTS: TPC was significantly higher in the group of patients with FIQ≥59 (16.9±2 vs. 15.6±4, p=0.02), whereas no differences between groups were observed according to FIQ≥70 (17.0±2 vs. 16.2±3, p=0.12) or FM type (16.8±3 for type II vs. 15.9±4 for type I, p=0.13). We observed a significant association between TPC and FIQ-job difficulty, pain, morning tiredness and stiffness dimensions (all p<0.05), yet it was not correlated with total score of FIQ, FIQ-anxiety, fatigue and depression dimensions (all p>0.05). Algometer score was lower in the FIQ≥70 (45.7±12 vs. 51.1±14, p=0.05) and FIQ≥59 (46.7±13 vs. 52.7±14, p=0.05) groups, and there were no difference between FM types (48.7±13 vs. 49.5±14 for type II and I respectively, p=0.81). Algometer score was not associated with total score of FIQ or FIQ dimensions (all p≥0.1). CONCLUSIONS: Widespread pain and pain hypersensitivity, as measured by TPC and algometer score, do not seem to be useful to characterise FM severity and symptomatology (measured by FIQ) in women.

Características de las dimensiones y subdimensiones de la personalidad en jóvenes jugadores de baloncesto / No disponible

Los trabajos que han destacado y predominado en las dos últimas décadas, en relación con el estudio de la personalidad, tanto en el ámbito deportivo (Hoyt, Rhodes, Hausenblas, Giacobbi, 2009; Ruiz, 2005) como extradeportivo: en psicología de las organizaciones, en psicología de la educación y en psicología clínica, confluyen en el modelo de los “Cinco Grandes Factores de la Personalidad” (MPBFQ). Para medirlos se han aplicado, principalmente, el modelo NEO- Personality Inventory (NEO-PI) y el cuestionario de personalidad Big Five (BFQ) de Caprara, Barbaranelli, Borgogni y Perugini (1993). El objetivo del presente trabajo es conocer los rasgos de la personalidad de los jóvenes jugadores de baloncesto a través del cuestionario de personalidad BFQ (Bermúdez, 1995) (AU)

Viejos y nuevos antiepilépticos en psiquiatría / Treatment of personality disorders with antiseizure drugs

Los antiepilépticos, especialmente la carbamazepina y el valproato, se han utilizado en el tratamiento de algunos trastornos psiquiátricos caracterizados por alteraciones afectivas y conductuales prácticamente desde su introducción en la clínica. Sin embargo, en la última década la aparición de una generación de anticonvulsivantes más seguros y manejables ha promovido el uso generalizado de estos agentes por parte de los psiquiatras. Los nuevos anticonvulsivantes son mejor tolerados y más seguros en comparación con los antiepilépticos clásicos y presentan una fármaco cinéticamás conveniente y menos interacciones farmacológicas. Aunque los anticonvulsivantes han demostrado ser eficaces en algunos trastornos psiquiátricos, especialmente en el tratamiento del trastorno afectivo bipolar, su eficacia en muchos otros trastornos no está todavía suficientemente contrastada mediante ensayos clínicos aleatorizados. De hecho, el uso de algunos anticonvulsivantes en muchas entidades psiquiátricas se basa en gran medida en estudios abiertos o en series de casos. Puesto que los mecanismos de acción de los diferentes anticonvulsivantes son diversos, su eficacia en diferentes trastornos psiquiátricos no es un efecto de clase. Por consiguiente hacen falta más estudios para definir con mayor nitidez qué agentes son eficaces y en qué trastornos presenta mayor utilidad cada uno de ellos (AU)

Antiepileptics, in particular carbamazepine and valproate, have been used in the treatment of some psychiatric disorders characterised by affective and behavioural disturbances practically from their introduction into the clinics. However, in the last decade the appearance of a generation of safer and more easy-to-use anticonvulsants has prompted the widespread use of these agents by psychiatrists. New anticonvulsants are better tolerated and safer when compared with the classic ones and they have more convenient pharmacokinetics and less drug-drug interactions. While anticonvulsants have shown to be effective in a number of psychiatric disorders (notably in the treatment of affective bipolar disorder) as yet, their efficacy in many other conditions has not been well established by means of randomized clinical trials. In fact, the use of some anticonvulsants in many psychiatric entities is largely based on open or case series studies. Since the mechanisms of action of the different anticonvulsants are diverse, their efficacy in different psychiatric disorders is not a class effect. Therefore, further studies are needed to clearly define which agents and to which disorders they are more useful (AU)

Aspectos clínicos prácticos del uso de anticomiciales / Practical clinical issues on the use of antiseizure drugs

Con la aparición de nuevos antiepilépticos más seguros y mejor tolerados, la utilización de los fármacos anticomiciales para el tratamiento de los trastornos psiquiátricos ha experimentado un notable auge en la última década. Desde la introducción de la vigabatrina en 1992, el arsenal de anticonvulsivantes disponibles se ha incrementado rápidamente a razón de prácticamente un nuevo fármaco cada 1-2 años. La rápida llegada al mercado de un número ingente de fármacos dificulta la actualización de conocimientos por parte del psiquiatra, máxime si se tiene en cuenta quela aplicación de los nuevos anticomiciales al tratamiento de los distintos trastornos psiquiátricos se fundamenta en gran medida en la experiencia clínica más que en los ensayos clínicos, por lo que no existen posologías ni pautas de uso estandarizadas. Sin embargo, es necesario que el psiquiatra conozca las peculiaridades de cada uno de estos fármacos en relación con su manejo rutinario, así como en situaciones especiales como el embarazo o la insuficiencia hepática o renal. El presente artículo recoge algunas recomendaciones acerca de los aspectos prácticos del uso de estos medicamentos, la mayoría de las cuales deriva necesariamente de la experiencia adquirida a partir de los pacientes epilépticos (AU)

With the advent of new antiepileptics safer and better tolerated, the use of anti-seizure drugs in the treatment of psychiatric disorders has experienced a remarkable growth in the last decade. Since the introduction of vigabatrin, in 1992, the armoury of available anticonvulsants has increased rapidly at a rate of practically one drug every one or two years. The fast arrival to the market of such a huge number of drugs hampers the psychiatrist keeping updated, especially when taking into account that the use of new anticonvulsants to treat different psychiatric disorders is based, to a great extent, on clinical experience rather than on clinical trials and thus, no standardised posologies or guidelines for their use are available. Nevertheless, psychiatrists need to know the peculiarities of each of these drugs regarding their routine management, as well as in special situations as pregnancy or renal or hepatic insufficiency. This article gives some recommendations about practical issues on the management of these drugs, most of which are necessarily based on experience gained from epileptic patients (AU)

Eficacia de la gabapentina en el tratamiento del dolor neuropático secundario a la lesión medular / Efficacy of the gabapentine in the treatment of the neuropathic pain due to spinal cord injury

en el tratamiento del dolor neuropático en pacientes afectos de lesión medular. Pacientes y métodos: Estudio prospectivo y comparativo en el que se incluyeron pacientes con lesión medular y dolor neuropático de acuerdo con la clasificación de Siddall y definición de la IASP, de más de tres meses de evolución y que no hubieran recibido tratamiento previo con gabapentina. Se valoraron y cuantificaron las características e intensidad del dolor neuropático y su interferencia con el sueño, así como su tolerabilidad a través de visitas seriadas. Resultados: Fueron incluidos 43 pacientes, 80,5 % varones con una edad media de 42 + 10,2 años. Se apreció mejoría en la descripción, valoración e intensidad del dolor en las escalas de Lattinen y McGill (p< 0,0001); así como en la interferencia con el sueño (p<0,0001) entre las dos visitas de seguimiento. La tolerabilidad del medicamento fue calificada como excelente en el 73,8%. Conclusiones: El tratamiento del dolor neuropático secundario a la lesión medular con gabapentina ofrece resultados satisfactorios en cuanto a la reducción de la intensidad y frecuencia del mismo; consigue disminuir la interferencia que produce en el sueño y constituye una alternativa segura, con pocos efectos secundarios

Objective: To evaluate the efficacy and tolerability of gabapentin in the treatment of neuropathic pain in patients with spinal cord injury. Patients and methods: Prospective and comparative study was designed. Individuals with spinal cord injury and neuropathic pain in accord with Siddall's classification and IASP's definition were included. The evolution of pain was longer than three moths and any patient had received previously treatment with gabapentine. Intensity and characteristic of neurophatic pain and its interference with sleep were measured and the tolerability was also assessed. Results: Fourty three patients were included, 80,5% men, 42+10,2 years aged. The results of description and intensity of pain in Lattinen and McGill scales were better (p<0,001), as also the interference with sleep (p<0,001) between the visits of control. Conclusions: The treatmet of neurophatic pain due to spinal cord with gabapentine offers satisfactory results to decrease its intensity and frecuency, to get a lower interference with sleep and it is a safe alternative with very few secundary effects

Fentanilo transdérmico en el tratamiento para el dolor neuropático del lesionado medular / Transdermal fentanyl in the treatment of neuropathic pain of spinal cord injured patient

Diseño. Estudio prospectivo, longitudinal y abierto. Objetivos. Valorar la eficacia analgésica del fentanilo transdérmico en dolor neuropático secundario a lesión medular comparándola con otros grupos de pacientes con dolor neuropático. Material y métodos. Se incluyeron pacientes con dolor neuropático afectos de lesión medular, conformándose un grupo control de enfermos amputados y afectos de un accidente cerebrovascular. Fueron registradas las características del dolor: intensidad según escala analógica visual y escala de Latineen, interferencia con el sueño y los efectos secundarios presentados. Se realizaron controles mediante visitas seriadas, monitorizándose los cambios manifestados respecto al dolor tras la administración del fentanilo transdérmico. En el estudio estadístico se emplearon la prueba de x 2 de Pearson y la prueba t, siendo considerados significativos valores de p < 0,05. Resultados. Treinta y dos pacientes fueron incluidos en el estudio, 20 lesionados medulares, 8 amputados y 4 pacientes afectos de un accidente cerebrovascular. La intensidad del dolor neuropático se redujo en ambos grupos, determinándose el descenso global en la escala analógica visual, de 7,54 a 3,8 a los tres meses (p < 0,05) y en la escala de Lattinen de 12,78 a 7,14 (p < 0,05). El descenso en la escala analógica visual fue menos intenso en el grupo de lesionados medulares, de 7,7 a 4,91 (p < 0,05), que en amputados y en pacientes con accidentes cerebrovasculares. Conclusiones. El fentanilo transdérmico es una alternativa terapéutica eficaz para el tratamiento del dolor neuropático secundario a lesión medular, si bien el descenso de intensidad del dolor es menor que en pacientes con dolor neuropático de otro origen

Design. Prospective, longitudinal and open-labeled study. Objectives. Assess analgesic efficacy of transdermal fentanyl in neuropathic pain secondary to spinal cord injury comparing it with other groups of patients with neuropathic pain. Material and methods. Patients with neuropathic pain affected by spinal cord injury were included, the control group being formed by amputee patients and those affected by cerebrovascular accident. The pain characteristics were recorded: intensity according to visual analogue scale and Lattinen scale, interference with sleep and side effects presented. Controls were conducted by seriated visits, monitoring the changes seen regarding pain after administration of transdermal fentanyl. Pearson's x 2 test and the t-test were used in the statistical study, values of p < 0.05 being considered as significant. Results. A total of 32 patients were included in the study, 20 with spinal cord injury, 8 amputees and 4 patients with cerebrovascular accident. Neuropathic pain intensity decreased in both groups, the global decrease on the visual analogue scale being determined from 7.54 to 3.8 at three months (p < 0.05) and on the Lattinen scale from 12.78 to 7.14 (p < 0.05). Decrease on the visual analogue scale was less intense in the spinal cord injured group, from 7.7 to 4.91 (p < 0.05), than in the amputees and in patients with cerebrovascular accidents. Conclusions. Transdermal fentanyl is an effective therapeutic alternative for treatment of neuropathic pain secondary to spinal cord injury although the decrease in pain intensity is less than in patients with neuropathic pain of another origin

[The modulatory role of neurokinins in affective behaviors]. / El papel modulador de las neuroquininas en las conductas afectivas.

Neurokinins (NK) are peptide molecules with modulatory actions on other neurotransmitter systems, notably the monoaminergic ones, within the central nervous system and peripheral tissues. A great deal of evidence supports a role for these substances, mainly for substance P and its main receptor NK1, in a number of physiologic and pathologic conditions, including affective and behavioral responses to stress. NK1 receptor antagonists have shown preclinical activity in several paradigms of anxiety and depression. Mutant mice lacking the NK1 receptor gene have an increased firing rate of dorsal raphe serotonergic neurons, an effect that can also be seen after the administration of substance P antagonists. When given chronically, NK1 antagonists promote an enhancement of serotonergic transmission in the hippocampus that seems to be mediated by interaction with other neurotransmission systems. Clinical efficacy of such drugs has also been demonstrated among patients with major depression, although the results have been inconclusive. More research is needed to elucidate the precise role these drugs could play in the treatment of affective disorders in the future.

El papel modulador de las neuroquininas en las conductas afectivas / The modulatory role of neurokinins in affective behaviors

Las neuroquininas (NK) son moléculas peptídicas que tienen una acción moduladora de otros sistemas neurotransmisores, entre ellos los monoaminérgicos, en el sistema nervioso central, así como en tejidos periféricos. Existen numerosas evidencias de que estas sustancias, y en especial la sustancia P y su principal receptor NK1, intervienen en numerosos procesos fisiológicos y patológicos, entre ellos las respuestas conductuales y afectivas al estrés. Los antagonistas del receptor NK1 han mostrado actividad preclínica en diversos modelos de ansiedad y de depresión. Los ratones mutantes con ausencia del gen del receptor NK1 presentan un aumento de la frecuencia de descarga de las neuronas serotoninérgicas del rafe dorsal, un efecto que también se observa tras la administración de antagonistas de la sustancia P. La administración crónica de antagonistas NK1 produce un aumento de la transmisión serotoninérgica en el hipocampo, que está mediada por la interacción con otros sistemas de neurotransmisión. También se ha demostrado la eficacia clínica de estos fármacos en pacientes con depresión mayor, aunque los resultados no han sido concluyentes. Son precisos más estudios para aclarar el papel que pueden desempeñar este tipo de fármacos en el tratamiento de los trastornos afectivos en el futuro

Neurokinins (NK) are peptide molecules with modulatory actions on other neurotransmitter systems, notably the monoaminergic ones, within the central nervous system and peripheral tissues. A great deal of evidence supports a role for these substances, mainly for substance P and its main receptor NK1, in a number of physiologic and pathologic conditions, including affective and behavioral responses to stress. NK1 receptor antagonists have shown preclinical activity in several paradigms of anxiety and depression. Mutant mice lacking the NK1 receptor gene have an increased firing rate of dorsal raphe serotonergic neurons, an effect that can also be seen after the administration of substance P antagonists. When given chronically, NK1 antagonists promote an enhancement of serotonergic transmission in the hippocampus that seems to be mediated by interaction with other neurotransmission systems. Clinical efficacy of such drugs has also been demonstrated among patients with major depression, although the results have been inconclusive. More research is needed to elucidate the precise role these drugs could play in the treatment of affective disorders in the future