Detección no sospechada de catinonas y piperacinas en pacientes consumidores de metanfetamina y anfetamina atendidos en servicios de urgencias hospitalarios / Detection of unsuspected cathinone and piperazine-type drugs in urine samples positive for methamphetamine and amphetamine collected in emergency departments

Objetivos. Determinar la incidencia de catinonas y piperazinas, no sospechadas y/o declaradas en consumidores de metanfetamina (MANF) y anfetamina (ANF) atendidos en servicios de urgencias hospitalarios (SUH) y comparar los perfiles clínicos y toxicológicos. Método. Estudio retrospectivo de pacientes con intoxicación aguda por drogas recreativas con MANF y ANF confirmadas analíticamente atendidos en 3 SUH entre marzo de 2019 y diciembre de 2020. Se detectaron por HPLC-MS/MS las catinonas [metilona, fluorometcatinona, mecedrona, fluorometanfetamina, mefedrona, metilendioxipirovalerona (MDPV)] y las piperazinas sintéticas [meta-clorofenilpiperazina (mCPP), trifluorometilfenilpiperazina (TFMPP)]. Resultados. Se incluyeron 39 pacientes: 24 (61,5%) en el grupo MANF y 15 (38,5%) en el ANF. En 11 (28,2%), se detectaron catinonas sintéticas (grupo CAT), 10 en el grupo MANF (8 mefedrona, 2 metilona) y 1 en el grupo ANF (1 mefedrona) (90,9% vs 9,1%; p = 0,028). Ninguno de los pacientes declaró consumo de catinonas. El nú- mero de drogas implicadas en la intoxicación fue superior en el grupo CAT (3,5 [1,13] vs 2,5 [1,40]; p = 0,036). El perfil clínico del grupo CAT fue: varón (90,9%), consumidor de MANF (90,9%) y usuario de chemsex (45,5%). El diagnóstico de VIH se asoció significativamente al grupo CAT (45,5% vs 10,7%; p = 0,028). Los pacientes del grupo CAT presentaron mayor ansiedad (72,7% vs 21,4%; p = 0,007). No se hallaron diferencias en su manejo clínico. Conclusiones. La detección de MANF debería considerarse un dato de sospecha de consumo de catinonas sintéticas, y en esos casos debería contemplarse la detección de nuevas sustancias psicoactivas de abuso.

Objectives. To detect the presence of unsuspected and/or undeclared cathinone and piperazine-type designer drugs in methamphetamine (METH) and amphetamine users treated in emergency departments, and to compare clinical and toxicologic profiles. Method. Retrospective observational study of emergency department patients treated for confirmed acute intoxication by recreational drugs (METH and amphetamines) between March 2019 and December 2020. We ordered high-performance liquid chromatography with tandem mass spectrometry to detect cathinones (methylone, fluoromethcathinone, mexedrone, fluoromethamphetamine, mephedrone, methylenedioxypyrovalerone) and synthetic piperazines (meta-chlorophenylpiperazine and trifluoromethylphenylpiperazine). Demographic, clinical, and toxicologic variables were analyzed with SPSS software (version 23). Results. Thirty-nine patients were included: 24 (61.5%) had used METH and 15 (38.5%) an amphetamine. Synthetic cathinones were detected in samples from 11 patients (28.2%), 10 (90.9%) in the METH group and 1 (9.1%) in the amphetamine group (P = .028). The METH users had taken mephedrone (8 patients) or methylone (2 patients); the amphetamine user had taken mephedrone. None of the patients had declared use of a cathinone; nor was use suspected. The mean (SD) number of substances involved was higher among users of cathinones (3.5 [1.13] vs 2.5 [1.40] in those who took no cathinones; P = .036). Among the cathinone users, 90.9% were men, 90.9% had used METH, and 45.5% had practiced chemsex. HIV positivity was significantly associated with cathinone use (in 45.5% vs 10.7% of those not using cathinones; P = .028). All 5 of the patients who had taken cathinones and also practiced chemsex were HIV positive. Significantly more patients who had taken cathinones presented with anxiety (72.7% vs 21.43%; P = .007). No differences in clinical management were found. [...]

BRCA2 deficiency increases sensitivity of medulloblastoma to Olaparib by inhibiting RAD51-mediated DNA damage repair system

PurposeBRCA2 defect exists in glioma and regulates drug resistance of glioma to chemotherapy. However, its role in medulloblastoma and the mechanism is not known. To investigate the effects of BRCA2 deficiency combined with Olaparib in medulloblastoma and the mechanism.MethodsBRCA2 was knocked down by RNAi technology and cell proliferation was detected by CCK-8 assay. Cell apoptosis was determined by FACS analysis when the in vivo role of BRCA2 was explored with xenograft mice model. Western blotting technology was used to explore the mechanism of BRCA2.ResultsKnockdown of BRCA2 enhanced the inhibitory effect of Olaparib on proliferation of Daoy and LN229 cells. The inhibition rate of Olaparib on Daoy or LN229 cells was 61.1%, 66.03% in shBRCA2 group, while it was 42.9%, 41.1% in shNC group. Overexpression of RAD51 partially reversed the effect of shBRCA2. In Daoy cells, apoptotic rate was 26.9% in Olaparib group and 58.9% in Olaparib/shBRCA2 group. However, it was 33.4% after RAD51 was overexpressed. It was the same in LN229 cells. In xenograft mice model, tumor volume in Olaparib and Olaparib/shBRCA2 group was 376.12 and 84.95mm3 when tumor weight was 0.46 g and 0.12 g. In addition, the level of RAD51, RAD50, MRE11, and NBS was increased by Olaparib alone but decreased reversely after knockdown of BRCA2 in Daoy cells.ConclusionsKnockdown of BRCA2 increases the sensitivity of medulloblastoma cells to Olaparib and strengthens the efficacy of Olaparib in vitro and in vivo. Knockdown of BRCA2 causes DNA damage repair by regulating RAD51-mediated signaling pathway in Daoy cells.

Preclinical and clinical development of palbociclib and future perspectives

Cyclin-dependent kinases (CDKs) play a key role in cell cycle regulation, which makes them a clear therapeutic target to interfere with cell division and proliferation in cancer patients. Palbociclib, a specific inhibitor of CDK4/6 with outstanding clinical efficacy data and limited toxicity, has been recently approved for the treatment of hormone receptor (HR)-positive human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer, either in combination with an aromatase inhibitor or in combination with fulvestrant in women who have received prior endocrine therapy. This review describes the mechanism of action, preclinical experiences and clinical data of palbociclib, with a special focus on integrating this data with the positioning of palbociclib in the current clinical guidelines for advanced HR-positive/HER2-negative breast cancer. Aspects of the ongoing major studies are also presented, as well as future prospects in the development of palbociclib

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Las nuevas drogas psicoactivas: populares y peligrosas / New psychoactive substances: Popular and dangerous

La popularidad de las nuevas sustancias psicoactivas (NPS) se ha incrementado a pesar del posible riesgo asociado a su uso. Ante un perfil sin precedentes, la puesta en común de datos toxicológicos es vital para entender los daños asociados al consumo, y disponer de revisiones bibliográficas constituye una importante herramienta para mantener un conocimiento actualizado. Esta revisión se ha enfocado hacia los efectos tóxicos y el riesgo para la salud, así como a proporcionar datos toxicológicos forenses sobre casos en que alguna NPS haya sido identificada y relacionada con la muerte

New psychoactive substances (NPS) have become increasingly popular, despite the potential harm associated with their use. Due to its unknown profile, it is of vital importance that any toxicological data collected is shared, in order to understand the effects associated with the use of these substances, and this data are shared with the scientific community in order to update the knowledge available. This report deals has two objectives. The first one is to focus on the toxicological effects and health risks linked to the use of NPS. The second one is to provide information for forensic toxicologists in cases where an NPS has been identified and may have been involved in the cause of death

Seguridad en el uso de antidepresivos: hiponatremia inducida con vortioxetina a propósito de un caso / Safety in the use of antidepressants: vortioxetine-induce hyponatremia in a case report

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Discrepancy in calcium release from the sarcoplasmic reticulum and intracellular acidic stores for the protection of the heart against ischemia/reperfusion injury

We and others have demonstrated a protective effect of pacing postconditioning (PPC) against ischemia/reperfusion (I/R) injury. However, the mechanisms underlying this protection are not completely clear. In the present study, we evaluated the effects of calcium release from the sarcoplasmic reticulum (SR) and the novel intracellular acidic stores (AS). Isolated rat hearts (n = 6 per group) were subjected to coronary occlusion followed by reperfusion using a modified Langendorff system. Cardiac hemodynamics and contractility were assessed using a data acquisition program, and cardiac injury was evaluated by creatine kinase (CK) and lactate dehydrogenase (LDH) levels. Hearts were subjected to 30 min of regional ischemia, produced by ligation of the left anterior descending (LAD) coronary artery, followed by 30 min of reperfusion. The hearts were also subjected to PPC (3 cycles of 30 s of left ventricle (LV) pacing alternated with 30 s of right atrium (RA) pacing) and/or were treated during reperfusion with agonists or antagonists of release of calcium from SR or AS. PPC significantly (P < 0.05) normalized LV, contractility, and coronary vascular dynamics and significantly (P < 0.001) decreased heart enzyme levels compared to the control treatments. The blockade of SR calcium release resulted in a significant (P < 0.01) recovery in LV function and contractility and a significant reduction in CK and LDH levels (P < 0.01) when applied alone or in combination with PPC. Interestingly, the release of calcium from AS alone or in combination with PPC significantly improved LV function and contractility (P < 0.05) and significantly decreased the CK and LDH levels (P < 0.01) compared to the control treatments. An additive effect was produced when agonism of calcium release from AS or blockade of calcium release from the SR was combined with PPC. Calcium release from AS and blockade of calcium release from the SR protect the heart against I/R. Combining calcium release from acidic stores or blockade of calcium release from the SR with PPC produced a synergistic protective effect (AU)

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Tyrosine-kinase mutations in c-KIT and PDGFR-alpha genes of imatinib naïve adult patients with gastrointestinal stromal tumours (GISTs) of the stomach and small intestine: relation to tumour-biological risk-profile and long-term outcome

BACKGROUND: The identification of activating mutations in either c-KIT cell surface growth factor receptor or platelet-derived growth factor receptor alpha (PDGFRA) has lead the way for the development of novel agents that selectively inhibit key molecular events in gastrointestinal stromal tumour (GIST) pathogenesis. The aim of this study was to investigate the role of c-KIT and PDGFRA gene mutations in primary resectable, imatinib naïve GISTs located in the stomach and small intestine. METHODS: All adult patients with GIST located in either stomach or small intestine who underwent surgical resection without prior imatinib (Glivec) treatment were included. DNA extraction and mutational analysis were performed. Mutational analyses were performed for c-KIT (exons 9, 11, 13, and 17) and the PDGFRA genes (exons 12, 14 and 18). Clinical and pathological parameters were analyzed in relation to the mutations in c-KIT and PDGFRA. RESULTS: A total of 38 patients who underwent surgery for GIST located in either the stomach (n = 24) or in the small intestines (n = 14) were included. Mutations were found in 31 of 38 (81.6 %) patients, with 24 (63.2 %) located in c-KIT and 7 (18.4 %) in the PDGRFA exons, respectively. Seven patients (18.4 %) were wildtype (WT). The most common mutation was in c-KIT exon 11. Incidentally found GISTs were significantly smaller (size >5 cm in 15 % for incidental vs. 71 % for symptomatic; OR of 13.4, 95 % CI 2.3-76.5; P = 0.001) and had lower mitotic rate (0 % for incidental vs. 44 % of the symptomatic; OR 0.52, 95 % CI 0.36-0.75; P = 0.005). Accordingly, the Fletcher grade was significantly better for incidental cases, with most having very low or low risk (85 %) in contrast to 19 of 25 (76 %) symptomatic cases showing moderate to high-risk features (OR 17.4, 95 % CI 2.98-101.7; P < 0.001). However, the distribution of c-KIT, PDGFRA and WT was not differently distributed between incidental and symptomatic GISTs. Long-term survival up to 25 years (median: 8 years) was best determined by Fletcher risk-score in the multivariate model (HR 14.1, 95 % CI 1.7-114.5; p = 0.013). CONCLUSIONS: Long-term survival in resected GISTs of the stomach and small intestine is best determined by Fletcher risk-score. Mitotic activity appears related to tumour size and young age at onset. Mutational status did not influence the clinical or tumour-specific features in this cohort (AU)

Drogas emergentes (I): las «smart drugs» / Emergent drugs (I): smart drugs

En los últimos años han ganado popularidad unaserie de nuevas drogas, conocidas como smart drugs olegal highs, fácilmente accesibles a través de tiendas online.Ello ocurre sobre todo en los segmentos jóvenesde la población, asociado a su consumo lúdico fundamentalmentedurante los fines de semana.En general son derivados sintéticos de productosnaturales, de los que apenas existe investigación clínicay que no son detectables en los laboratorios de loshospitales.Tres de estos productos, el BZP (1-benzilpiperacina),la mefedrona (4-metilcatinona) y el Spice sonprobablemente los más utilizados en Europa. Los dosprimeros se consumen como alternativas al éxtasis y lacocaína, y se caracterizan por producir un cuadro clínicode tipo simpaticomimético, en ocasiones de consecuenciasgraves, con convulsiones e incluso muerte. ElSpice (mezcla de hierbas con cannabinoides sintéticoscomo el JWH-018, el JWH-073 y el CP 47,497-C8) estáocasionando cuadros de dependencia y esquizofrenia.Aunque las drogas emergentes poseen un aurade seguridad, cada vez hay más experiencia sobre susefectos secundarios(AU)

In recent years, a series of new drugs, known assmart drugs or legal highs, have gaining in popularity.They are easily obtainable through online shops. Thisis happening amongst younger segments of the populationand is associated with recreational consumption,at weekends.In general, they are synthetic derivatives of naturalproducts. There has been hardly any clinical researchinto them and they are not detectable in hospital laboratories.Three of these products, BZP (1-benzylpiperazine),mefedrone (4-methylmethcathinone) and Spice are probablythe most widely used in Europe. The first two areconsumed as an alternative to ecstasy and cocaine andare characterized by their producing a clinical profile ofa sympathetic mimetic type; on occasion, they have seriousconsequences, with convulsions and even death.Spice (a mixture of herbs with synthetic cannabinoidssuch as JWH-018, JWH-073 and CP 47497-C8) is givingrise to profiles of dependence and schizophrenia.Although the emergent drugs have an aura of safety,there is an increasing amount of experience on theirsecondary effects(AU)

Clinical implications of KIT and PDGFRA genotyping in GIST

Gastrointestinal stromal tumours (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract. GISTs are characterised by the expression of KIT, a type III tyrosine kinase receptor, and the presence of mutations in KIT or PDGFRA in about 80-85% of cases. The primary treatment for GIST is surgery, which cures most patients with low- or intermediate-risk tumours. The introduction of the kinase inhibitor imatinib mesylate, and sunitinib in second line, against KIT and PDGFRA has provided the first evidence of directed therapy in GIST. The aim of this review is to highlight the growing evidence that KIT and PDGFRA genotyping provides valuable information for the clinical management of GIST patients. We show that KIT and PDGFRA genotyping has emerged as one of the principal factors in the evaluation of GISTs, particularly in those tumours that are clearly malignant or have a high risk of recurrence. In addition to helping establish the diagnosis of GIST in unusual cases, genotyping can be very useful to physicians and patients in deciding on imatinib dose, in estimating the likelihood and duration of benefit, and potentially in selecting second-line therapies (AU)

Interacciones medicamentosas de etravirina / Etravirine drug interactions

Etravirina (ETR) es un fármaco perteneciente a la familia de los inhibidores de la transcriptasa inversa no análogos de nucleósidos (ITINAN), con actividad antiviral en situaciones de resistencia a los ITINAN de primera generación. Las interacciones farmacológicas producidas por ETR se deben a su efecto dual sobre el sistema CYP450. Es inductor de la actividad de CYP3A4 e inhibidor de la de CYP2C9 y CYP2C19. ETR presenta escasas interacciones farmacológicas clínicamente significativas, entre las que destacan los inhibidores de la proteasa sin potenciar, los ITINAN efavirenz y nevirapina, ritonavir a dosis plena y tipranavir/ritonavir. La interacción con fosamprenavir/ritonavir no es clínicamente significativa, aunque hay una escasa variación de sus valores plasmáticos al administrarse de manera conjunta con ETR. No presenta interacciones con darunavir/ritonavir

Etravirine (ETR) belongs to the family of non-nucleoside analogue reverse transcriptase inhibitors (NNRTIs), with antiviral activity in patients with resistance to first-generation NNRTIs. The drug interactions caused by ETR are due to its dual effect on the CYP450 system. ETR acts as an inducer of CYP3A4 and inhibitor of CYP2C9 and CYP2C19. This drug shows few clinically significant drug interactions, the most important of which involve the unboosted protease inhibitors, the NNRTIs efavirenz and nevirapine, full-dose ritonavir and tipranavir/ritonavir. Interaction with fosamprenavir/ritonavir is not clinically significant, although their plasma levels vary slightly when used in combination with ETR. ETR shows no interactions with darunavir/ritonavir

Un caso de liquen plano asociado a tratamiento con imatinib / A case of lichen planus associated to treatment with imatinib

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Efecto del sildenafilo en un sujeto con miocardiopatía hipertrófica obstructiva candidato a trasplante cardíaco / Effect of sildenafile in patient with obstructive hypertrophic cardiomyopathy candidated to cardiac transplantation

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Effect of a heterotrimeric G protein α subunit on conidia germination, stress response, and roquefortine C production in Penicillium roqueforti

Heterotrimeric G protein signaling regulates many processes in fungi, such as development, pathogenicity, and secondary metabolite biosynthesis. For example, the Galpha subunit Pga1 from Penicillium chrysogenum regulates conidiation and secondary metabolite production in this fungus. The dominant activating allele, pga1G42R, encoding a constitutively active Pga1 Galpha subunit, was introduced in Penicillium roqueforti by transformation, resulting in a phenotype characterized by low sporulation and slow growth. In this work, the effect of the constitutively active Pga1G42R Galpha subunit on conidial germination, stress tolerance, and roquefortine C production of P. roqueforti was studied. Pga1G42R triggered germination in the absence of a carbon source, in addition to negatively regulating thermal and osmotic stress tolerance. The presence of the Pga1G42R Galpha subunit also had an important effect on roquefortine C biosynthesis, increasing production and maintaining high levels of the mycotoxin throughout a culture period of 30 days. Together, the results suggest that G protein-mediated signaling participates in the regulation of these three processes in P. roqueforti (AU)

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Drogas de abuso y patrones de consumo emergentes / Abusive drugs and emerging patterns of consumption

Las tendencias emergentes en materia de drogas a menudo reflejan, potencian o sustituyen tendencias tradicionales. Los desarrollos de la tecnología de la información y los medios de comunicación, particularmente Internet, proporcionan canales que facilitan la difusión de nuevas tendencias y permiten expresar diferentes opiniones en relación con el consumo de drogas y los riesgos asociados. La evolución más significativa en relación con las nuevas sustancias psicoactivas durante los últimos años es la expansión de nuevos derivados de la piperazina: BZP (1-benzilpiperazina), mCPP (1-(3-clorofenil)piperazina) and TFMPP (1-(3-trifluorometilfenil)piperazina). Otros grupos de nuevas sutancias psicoactivas son: drogas de club (ketamina, GHB o ácido gamma hidroxibutírico, y sus precursores gamma-butirolactona y 1,4-butanediol, GBL y 1,4-BD, respectivamente), drogas inteligentes (nootrópicos) y esteroides anabolizantes. Este artículo informa sobre evoluciones recientes en materia de consumo ilegal de sustancias psicoactivas que los indicadores clave sobre drogas no abordan de forma rutinaria y que solo recientemente se han identificado (AU)

Emerging drugs trends often mimic, expand on, or substitute previously popular drug trends. Developments in information technology and communication media, particularly the Internet, provide channels that facilitate the diffusion of new trends and allow the expression of diverse opinions about drug use and the associated risks. The most significant development relating to new psychoactive substances in recent years is the spread of various novel piperazine derivatives: BZP (1-benzylpiperazine), mCPP (1-(3-chlorophenyl)piperazine) and TFMPP (1-(3-trifluoromethylphenyl)piperazine). Other groups of new psychoactive substances are: club drugs (ketamine, GHB or gamma hydroxybutyric acid, and its precursors gamma-butyrolactone and 1,4-butanediol, GBL and 1,4-BD, respectively), smart drugs (nootropics) and anabolic steroids. This article reports on recent developments in the illicit use of psychoactive substances that are not routinely addressed by the key drug indicatorsand have only recently been identified (AU)

Cost-effectiveness analysis of sunitinib in patients with metastatic and/or unresectable gastrointestinal stroma tumours (GIST) after progression or intolerance with imatinib

INTRODUCTION: Sunitinib is a multiselective oral inhibitor of several tyrosine-kinase receptors that has demonstrated its efficacy in patients with metastatic and/or unresectable gastrointestinal stroma tumours (GIST) who were resistant to or intolerant to previous treatment with imatinib. The purpose of this study is to assess the cost-effectiveness of sunitinib vs. best supportive care (BSC) in GIST as a second- line treatment, from the perspective of the Spanish National Health System. MATERIALS AND METHODS: A Markov model was used to assess the cost effectiveness of sunitinib (50 mg/day, 4 weeks "on" and 2 weeks "off") vs. BSC in GIST as a second-line treatment. Transition probabilities between the three health states considered in the model (progression-free survival (PFS), progression and death) were obtained from a clinical trial [Demetri et al. (2006) Lancet 368:1329-1338]. Health resource data (drugs, medical visits, laboratory and radiology tests, palliative care and adverse events) were obtained from an expert panel. Deterministic and probabilistic sensitivity analyses were conducted. RESULTS: Projected PFS years, life years (LY) and quality of life adjusted years (QALYs) were higher for sunitinib compared with BSC: 0.50 vs. 0.24, 1.59 vs. 0.88 and 1.00 vs. 0.55. Mean costs per patient were 23,259 euros with sunitinib and 1,622 euros with BSC. The incremental cost-effectiveness ratios (ICERs) obtained were: 4,090 euros/month PFS, 30,242 euros/LY and 49,090 euros/QALY gained. The most influential variables for the results were the efficacy and unit cost of sunitinib. CONCLUSIONS: According to the efficiency thresholds for oncology patients in developed countries, sunitinib is considered cost-effective vs. BSC with acceptable costs per LY and QALY gained (AU)

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Repercusiones de la retirada de la tioridazina / Repercussions of the withdrawal of thioridazine

Introducción. Como consecuencia de la retirada del mercado de la tioridazina, pacientes que habían sido tratados con este fármaco requieren un nuevo abordaje terapéutico. Observamos casos de ingreso en la unidad de agudos por descompensación tras la retirada de tioridazina y que presentan difícil manejo terapéutico. Se realiza una descripción de las características clínicas y de la pauta farmacológica que lleva a la estabilización del paciente. Resultados. La muestra obtenida en nuestra unidad es de 15 pacientes con una media de 20 años de estabilidad previa a la retirada de tioridazina. Representan un 6% de todos los pacientes en tratamiento con tioridazina durante2005 en nuestra región sanitaria. Presentaron un perfil psicopatológico común: patrón afectivo sobreañadido a la clínica psicótica, predominando labilidad emocional y tendencia a hipertimia de difícil manejo farmacológico. En un 27%se consiguió estabilidad con fenotiazinas piperazinas en monoterapia; en un 60 % requirieron la asociación con eutimizante y/o a antipsicótico atípico. Un 20% se estabilizaron con antipsicóticos atípicos en monoterapia. En un 40% pauta moseutimizante para manejar la inestabilidad afectiva y un 27 % presentaron respuesta a tratamiento con terapia electroconvulsiva (TEC), que se prescribe de segunda elección debido a la resistencia al tratamiento farmacológico asociado a gravedad. Conclusiones. Proponemos iniciar un tratamiento con el grupo de fenotiazinas piperazinas valorando la introducción de un eutimizante y/o TEC. Se ha producido un 33% de reingresos; un 40 % de los casos han requerido centros demedia/larga estancia y registramos un suicidio consumado. Observamos un elevado coste tanto de recursos asistenciales, económicos como de calidad de vida (autonomía, habilidades sociales y nivel cognitivo) en nuestra muestra tras la retirada de tioridazina (AU)

Introduction. As a consequence of the withdrawal of thioridazine from the market, patients who have been treated with this drug require a new therapeutic approach. We have observed patients who require admission to acute unit due to decompensation resulting from the withdrawal of thioridazine who present a difficult management of therapeutic regime. The clinical characteristics and drug treatment needed to stabilize the patient are described. Results. The sample obtained in our unit included15 patients with a mean of 20 years of stability prior to withdrawal of thioridazine. This represents 6% of all the patients treated with thioridazine in 2005 in our healthcare area. They had a common psychopathological profile: affective pattern in addition to the psychotic symptomatology with predominance of emotional lability and hypomaniac tendency which is difficult to control pharmacologically. Clinical stabilization was obtained in 27% of patients by means of piperazine phenothiazines in monotherapy. An association with mood stabilizer and/or an atypical antipsychotic in 60% of patients was needed. In 40 % we prescribed a mood stabilizer to manage affective instability and 27% responded to electroconvulsive therapy (ECT) treatment, which is indicated as a second option due to resistance to pharmacological treatment and/or presenting a serious condition. Conclusions. We propose starting treatment with a group of piperazine phenothiazines, evaluating the introducing of mood stabilizers and/or ECT in each case. There have been 33% re-admissions, 40% of which required medium/long-term stay centers and one of which committed suicide. We demonstrate a high cost in terms of care, economic resources and of quality of life (autonomy, social skills and cognitive level) in our sample as a result of Meleril® (thioridazine) withdrawal of the market (AU)

La PET/TAC con 18F-FDG en la evaluación de la respuesta de los tumores del estroma gastrointestinal al tratamiento con imatinib / 18F-FDG PET/CT in response evaluation of gastrointestinal stromal tumours treated with imatinib

Objetivo. Diferentes trabajos han demostrado la efectividad del tratamiento adyuvante con mesilato de imatinib en el tumor del estroma gastrointestinal (GIST) irresecable, metastásico o recidivado. Hemos estudiado, retrospectivamente, el papel de la PET/TAC con 18F-FDG en la valoración de la respuesta del GIST al tratamiento con imatinib. Material y métodos. El estudio incluyó 8 pacientes consecutivos con GIST confirmado por cirugía (4 estómago, 2 intestino delgado, 1 intestino delgado y peritoneo y 1 recto) a los cuales se les realizaron 18 PET/TAC con 18F-FDG después de iniciar el tratamiento con mesilato de imatinib (400 mg/día o dosis mayores si se detectó progresión). La PET/TAC se adquirió a los 60-90 minutos después de la administración intravenosa de 333-707 MBq de 18F-FDG. Se realizó un análisis visual y semicuantitativo (standardized uptake value [SUV]) de las imágenes. La respuesta a la terapia se valoró siguiendo las recomendaciones de la EORTC para la PET. Los resultados se confirmaron por seguimiento clínico, hallazgos radiológicos o histología. Resultados. La respuesta al imatinib fue completa en 5 pacientes. Cuatro de ellos tuvieron adenopatías abdominales, asociadas a metástasis hepáticas en dos; el otro paciente tuvo una masa tumoral residual. La respuesta fue parcial (disminución del SUV y de la extensión de la captación de FDG) en un paciente con nódulos pulmonares. Se observó progresión de la enfermedad en un paciente por la aparición de nuevas metástasis hepáticas en la PET/TAC. Una paciente no respondió a la terapia y tuvo múltiples implantes peritoneales y una masa abdominal, falleciendo a los 2 meses de la PET/TAC. Conclusión. La PET/TAC con 18F-FDG identificó el grado de respuesta del GIST a la terapia con imatinib. En los pacientes que respondieron al tratamiento se observó la normalización de la captación de FDG o un descenso en el SUV de las lesiones (AU)

Objective. Several studies have demonstrated the effective use of adjuvant treatment with Imatinib mesylate for unresectable, metastatic or recurrent gastrointestinal stromal tumours (GIST). We retrospectively evaluated the role of 18F-FDG PET/CT scanning in assessing the response of GIST patients to imatinib mesylate therapy. Materials and methods. Eight consecutive patients with GIST confirmed by surgery (4 stomach, 2 small bowel, 1 small bowel and peritoneum, and 1 rectum) underwent eighteen 18F-FDG PET/CT imaging after beginning imatinib mesylate therapy (400 mg/day or greater if disease progression). PET/CT scan was acquired 60-90 minutes after the intravenous injection of 333-707 MBq of 18F-FDG. Visual and semiquantitative (standardized uptake value [SUV]) analysis of images was performed. Response to therapy was assessed according to EORTC recommendations for PET. Results were confirmed by clinical follow-up, radiographic findings or histological analysis. Results. Complete response to imatinib mesylate was observed in 5 patients. Four had abdominal lymph nodes, associated with liver metastases in 2, and the other had a residual tumour mass. Partial response (reduction in SUV and in the extent of FDG uptake) was demonstrated in a patient with lung nodules. Disease progression was observed in one patient who had developed new liver metastases on the PET/CT scan. One patient with multiple peritoneal implants and abdominal mass was a non-responder and died 2 months after the 18F-FDG PET/CT. Conclusion. 18F-FDG PET/CT scan identified the degree of GIST response to imatinib therapy. Patients who responded to therapy showed normalisation of FDG uptake or a decrease in the SUV of lesions (AU)

Seguridad de ziprasidona en intoxicación: a propósito de un caso / Ziprasidone security in overdose: one case report

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Utilidad de la FDG-PET en la evaluación precoz de la eficacia de imatinib (Glivec) en el tratamiento de tumores del estroma gastrointestinal / Utility of FDG-PET for early evaluation of efficiency of imatinib mesylate (Glivec) in the treatment of gastrointestinal stromal tumors

El manejo de los tumores del estroma gastrointestinal, definidos como neoplasias mesenquimales c-Kit positivas, ha cambiado rápidamente en los últimos cinco años. El mesilato de imatinib (Glivec®) es el tratamiento estándar de los tumores del estroma gastrointestinal irresecables o metastáticos. El imatinib debe administrarse hasta el desarrollo de intolerancia o la progresión de la enfermedad. No es infrecuente que los tumores del estroma gastrointestinal aumenten de tamaño durante los primeros meses de tratamiento, de ahí el valor limitado de los criterios convencionales de evaluación de respuesta de los tumores sólidos para determinar la eficacia del imatinib durante este período. La tomografía de emisión de positrones empleando 18F-fluorodesoxiglucosa ha demostrado tener una alta sensibilidad en la evaluación precoz de la respuesta tumoral al imatinib. Presentamos el caso de una mujer de 53 años diagnosticada de recidiva de tumor del estroma gastrointestinal 18 meses después de finalizar tratamiento adyuvante con imatinib. Tras 72 horas de tratamiento con imatinib el tumor mostraba en la tomografía de emisión de positrones una disminución en la captación de 18F-fluorodesoxiglucosa

The management of gastrointestinal stromal tumors, usually defined as c-KIT-positive mesenchimal neoplasias, has evolved very rapidly in the last five years. Imatinib mesylate (Glivec®) is the standard treatment in unresectable or metastatic gastrointestinal stromal tumors. Imatinib should be given until development of intolerance or progressive disease. It is not uncommon for gastrointestinal stromal tumors to become larger during the early post-treatment phase and conventional response to treatment criteria in solid tumors have a limited value for evaluation the efficiency of imatinib in this period. FDG-PET has proven to be highly sensitive in detecting early response tumor. A 53-year old woman was diagnosed of relapse gastrointestinal stromal tumor 18 months after adyuvant imatinib mesylate finished. Imatinib was started and 72 hours later the tumor showed a decrease of fluorodeoxyglucose F18 uptake on positron emission tomography scan