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A high-fidelity synthetic diagnostic has been developed for the ITER core x-ray crystal spectrometer diagnostic based on x-ray ray tracing. This synthetic diagnostic has been used to model expected performance of the diagnostic, to aid in diagnostic design, and to develop engineering tolerances. The synthetic model is based on x-ray ray tracing using the recently developed xicsrt ray tracing code and includes a fully three-dimensional representation of the diagnostic based on the computer aided design. The modeled components are: plasma geometry and emission profiles, highly oriented pyrolytic graphite pre-reflectors, spherically bent crystals, and pixelated x-ray detectors. Plasma emission profiles have been calculated for Xe44+, Xe47+, and Xe51+, based on an ITER operational scenario available through the Integrated Modelling & Analysis Suite database, and modeled within the ray tracing code as a volumetric x-ray source; the shape of the plasma source is determined by equilibrium geometry and an appropriate wavelength distribution to match the expected ion temperature profile. All individual components of the x-ray optical system have been modeled with high-fidelity producing a synthetic detector image that is expected to closely match what will be seen in the final as-built system. Particular care is taken to maintain preservation of photon statistics throughout the ray tracing allowing for quantitative estimates of diagnostic performance.
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Based on data for N = 2,756 children (1,410 girls; Mage = 8.10 years) from 16 data sets spanning five nations, this study investigated relations between national gender disparities and children's beliefs about gender and academic subjects. One national-level gender disparity involved inequalities in socioeconomic standing favoring adult males over females (U.N. Human Development Index). The other involved national-level gaps in standardized math achievement, favoring boys over girls (Trends in International Mathematics and Science Study Grade 4). Three novel findings emerged. First, girls' results from a Child Implicit Association Test showed that implicit associations linking boys with math and girls with reading were positively related to both national male advantages in socioeconomic standing and national boy advantages in Trends in International Mathematics and Science Study. Second, these relations were obtained for implicit but not explicit measures of children's beliefs linking gender and academic subjects. Third, implicit associations linking gender to academic subjects increased significantly as a function of children's age. We propose a psychological account of why national gender disparities are likely to influence children's developing implicit associations about gender and academic subjects, especially for girls. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
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It is well established that solutions of both polymeric and oligomeric κ-carrageenan exhibit a clear change in optical rotation (OR), in concert with gel-formation for polymeric samples, as the solution is cooled in the presence of certain ions. The canonical interpretation - that this OR change reflects a 'coil-to-helix transition' in single chains - has seemed unambiguous; the solution- or 'disordered'-state structure has ubiquitously been assumed to be a 'random coil', and the helical nature of carrageenan in the solid-state was settled in the 1970s. However, recent work has found that κ-carrageenan contains substantial helical secondary structure elements in the disordered-state, raising doubts over the validity of this interpretation. To investigate the origins of the OR, density-functional theory calculations were conducted using atomic models of κ-carrageenan oligomers. Changes were found to occur in the predicted OR owing purely to dimerization of chains, and - together with the additional effects of slight changes in conformation that occur when separated helical chains form double-helices - the predicted OR changes are qualitatively consistent with experimental results. These findings contribute to a growing body of evidence that the carrageenan 'disorder-to-order' transition is a cooperative process, and have further implications for the interpretation of OR changes demonstrated by macromolecules in general.
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Neutral [X-{Ir2 }-{Ir2 }-X] (X=Cl, Br, SCN, I) and dicationic [L-{Ir2 }-{Ir2 }-L]2+ (L=MeCN, Me2 CO) tetrametallic iridium chains made by connecting two dinuclear {Ir2 } units ({Ir2 }=[Ir2 (µ-OPy)2 (CO)4 ], OPy=2-pyridonate) by an iridium-iridium bond are described. The complexes exhibit fractional averaged oxidation states of +1.5 and electronic delocalization along the metallic chain. While the axial ligands do not significantly affect the metal-metal bond lengths, the metallic chain has a significant impact on the iridium-L/X bond distances. The complexes show free rotation around the unsupported iridium-iridium bond in solution, with a low-energy transition state for the chloride chain. The absorption spectra of these complexes show characteristic bands at 438-504â nm, which can be fine-tuned by varying the terminal capping ligands.
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OBJECTIVES: Our objective was to reinforce clinical knowledge of hearing impairment in KBG syndrome. KBG syndrome is a rare genetic disorder due to monoallelic pathogenic variations of ANKRD11.The typical phenotype includes facial dysmorphism, costal and spinal malformation and developmental delay. Hearing loss in KBG patients has been reported for many years, but no study has evaluated audiological phenotyping from a clinical and an anatomical point of view. METHODS: This French multicenter study included 32 KBG patients with retrospective collection of data on audiological features, ear imaging and genetic investigations. RESULTS: We identified a typical audiological profil in KBG syndrome: conductive (71%), bilateral (81%), mild to moderate (84%) and stable (69%) hearing loss, with some audiological heterogeneity. Among patients with an abnormality on CT imaging (55%), ossicular chain impairment (67%), fixation of the stapes footplate (33%) and inner-ear malformations (33%) were the most common abnormalities. CONCLUSION: We recommend a complete audiological and radiological evaluation and an ENT-follow up in all patients presenting with KBG Syndrome. Imaging evaluation is necessary to determine the nature of lesions in the middle and inner ear.
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Anomalías Múltiples , Enfermedades del Desarrollo Óseo , Sordera , Discapacidad Intelectual , Anomalías Dentarias , Humanos , Anomalías Múltiples/genética , Discapacidad Intelectual/genética , Enfermedades del Desarrollo Óseo/genética , Anomalías Dentarias/genética , Facies , Estudios Retrospectivos , Proteínas Represoras/genética , FenotipoRESUMEN
Piperazine rings are essential motifs frequently found in commercial drugs. However, synthetic methodologies are mainly limited to N-substituted piperazines, preventing structural diversity. Disclosed herein is a straightforward catalytic method for the synthesis of complex C-substituted piperazines based on an uncommon head-to-head coupling of easily prepared imines. This 100% atom-economic process allows the selective formation of a sole diastereoisomer, a broad substrate scope, and a good functional group tolerance employing a bench-stable iridium catalyst under mild reaction conditions. Key to the success is the addition of N-oxides to the reaction mixture, as they notably enhance the catalytic activity and selectivity.
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Alzheimer's disease (AD) is the most common cause of dementia among older adults. APOE3 Christchurch (R136S, APOE3Ch ) variant homozygosity was reported in an individual with extreme resistance to autosomal dominant AD due to the PSEN1 E280A mutation. This subject had a delayed clinical age at onset and resistance to tauopathy and neurodegeneration despite extremely high amyloid plaque burden. We established induced pluripotent stem (iPS) cell-derived cerebral organoids from this resistant case and from a non-protected kindred control (with PSEN1 E280A and APOE3/3 ). We used CRISPR/Cas9 gene editing to successfully remove the APOE3Ch to wild type in iPS cells from the protected case and to introduce the APOE3Ch as homozygote in iPS cells from the non-protected case to examine causality. We found significant reduction of tau phosphorylation (pTau 202/205 and pTau396) in cerebral organoids with the APOE3Ch variant, consistent with the strikingly reduced tau pathology found in the resistant case. We identified Cadherin and Wnt pathways as signaling mechanisms regulated by the APOE3Ch variant through single cell RNA sequencing in cerebral organoids. We also identified elevated ß-catenin protein, a regulator of tau phosphorylation, as a candidate mediator of APOE3Ch resistance to tauopathy. Our findings show that APOE3Ch is necessary and sufficient to confer resistance to tauopathy in an experimental ex-vivo model establishing a foundation for the development of novel, protected case-inspired therapeutics for tauopathies, including Alzheimer's.
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OBJECTIVE: Iloprost (ILO) is recommended for the treatment of systemic sclerosis (SSc) microangiopathy, but there is no common consensus on its optimal dosage. The aim of this study is to evaluate the kinetics of response to ILO administered in a daily outpatient scheme in SSc subjects using laser speckle contrast analysis (LASCA). METHOD: Adult SSc patients in stable therapy with ILO administered for 6 h for 2 consecutive days every 4 weeks were enrolled. Peripheral finger perfusion was assessed by LASCA. Each patient underwent five LASCA evaluations: before and after each day of ILO (D1pre, D1post, D2pre, and D2post) and after 4 weeks (D30). RESULTS: Twenty-seven SSc patients (77.8% female, mean age 61.5 years) were enrolled. LASCA showed an increase in perfusion at the end of each ILO course, but on the second day (both D1pre vs D2pre and D2pre vs D2post) the increase was no longer significant in half of the fingers. Moreover, compared to D1post, at the beginning of the second ILO day most of the fingers had already shown a significant reduction in perfusion. After 1 month, there were no statistically significant differences between the perfusion values of D1pre and D30. CONCLUSION: This LASCA study highlights the transience of the vasoactive effect of ILO, with a perfusion benefit that is completely lost after 1 month. The brevity of the perfusion effect of ILO and the use of LASCA are elements to consider in the design of future SSc trials to determine the optimal ILO dosage.
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Iloprost , Esclerodermia Sistémica , Adulto , Humanos , Femenino , Persona de Mediana Edad , Masculino , Iloprost/farmacología , Iloprost/uso terapéutico , Dedos , Capilares , Esclerodermia Sistémica/tratamiento farmacológico , Rayos LáserRESUMEN
Summary: Background. Kikuchi-Fujimoto Disease (KFD) or histiocytic necrotizing lymphadenitys is a rare disorder characterized by subacute necrotizing regional lymphadenopathy. It is usually presented as painful cervical nodes and associated with fever, headache, night sweats, nausea, vomiting and sore throat. Etiology of KFD is still unclear, two theories have been proposed: infections and autoimmune origin. Due to recent reports of KFD related to COVID-19 vaccination, the novelty of the mechanism of these vaccines and the immunomodulated role of both matters, a literature and adverse event databases review was carried out in order to shed light on the relationship between these two matters. Methods. A search in the Spanish and the European adverse events databases (FEDRA and Eudravigilance) was performed. Search criteria were any drug and the diagnosis "Histiocytic necrotizing lymphadenitis" according to the Medical Dictionary for Medical Activities version 25.0. All adverse events registered as June 2, 2022, were included. Results. FEDRA encompassed two KFD reports, one related to a mRNA COVID-19 vaccine. Eudravigilance included a total of 62 KFD cases, 14 of them associated to COVID-19 vaccines and eight to other vaccines. Conclusions. Pharmacovigilance is of utter importance in detecting adverse events caused by new vaccines. More research is needed to establish a final connection between KFD and COVD-19 vaccines, but due to the physiopathology of the condition, how vaccines stimulate the immune system and the high number of reported KFD cases with vaccines given its rare incidence, it is plausible to think that both entities are related.
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Vacunas contra la COVID-19 , COVID-19 , Linfadenitis Necrotizante Histiocítica , Humanos , COVID-19/prevención & control , Vacunas contra la COVID-19/efectos adversos , Linfadenitis Necrotizante Histiocítica/etiología , Linfadenitis Necrotizante Histiocítica/complicaciones , Farmacovigilancia , Vacunación/efectos adversosRESUMEN
Resumen Introducción: el estudio analizó (a) las diferencias entre madres y padres en sus actividades matemáticas en el hogar y en otros factores del ambiente matemático (actitudes, ansiedad, creencias y expectativas matemáticas) y (b) la asociación entre los factores del ambiente matemático y las actividades matemáticas en el hogar. Método: participaron 266 familias de niños y niñas chilenos de primer a tercer grado de primaria (edad promedio = 93.35 meses, DE = 11.45 meses). Ambos padres contestaron un cuestionario sobre matemáticas en el hogar. Resultados: las madres reportaron realizar actividades matemáticas con mayor frecuencia que los padres. Análisis de ecuaciones estructurales mostraron que las actividades matemáticas realizadas por los padres se relacionaron con sus creencias, actitudes y expectativas matemáticas; mientras que las de las madres se relacionaron con sus creencias, actitudes y género de los niños. Conclusiones: los hallazgos aportan a la comprensión del ambiente matemático en el hogar.
Abstract Introduction: The study analyzes (a) the differences between mothers and fathers in their home math activities and home math environment factors (math attitudes, anxiety, beliefs, and expectations) and (b) the associations among the home math environment factors and home math activities of Chilean families. Method: Participants were 266 families of boys and girls attending grades 1-3 (mean age = 93.35 months, DS = 11.45 months). Both parents of each child independently answered a home math questionnaire. Results: Mothers reported doing more math activities with their children than fathers. The structural equation model analyses showed that the frequency with which fathers engage in home math activities was related to their math beliefs, attitudes, and expectations, whereas maternal home math activities were related to their beliefs, attitudes, and the gender of the child. Conclusions: The findings contribute to the understanding of the home math environment.
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Monochromators for synchrotron radiation beamlines typically use perfect crystals for the hard X-ray regime and gratings for soft X-rays. There is an intermediate range, typically 1-3â keV (tender X-rays), which common perfect crystals have difficulties covering and gratings have low efficiency, although some less common crystals with high d-spacing could be suitable. To evaluate the suitability of these crystals for a particular beamline, it is useful to evaluate the crystals' performance using tools such as ray-tracing. However, simulations for double-crystal monochromators are only available for the most used crystals such as Si, Ge or diamond. Here, an upgrade of the SHADOW ray-tracing code and complementary tools in the OASYS suite are presented to simulate high d-spacing crystals with arbitrary, and sometimes complex, structures such as beryl, YB66, muscovite, etc. Isotropic and anisotropic temperature factors are also considered. The YB66 crystal with 1936 atomic sites in the unit cell is simulated, and its applicability for tender X-ray monochromators is discussed in the context of new low-emittance storage rings.
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Objetivo: Analizar la eficacia terapéutica, seguridad y valor pronóstico de diferentes biomarcadores de la radioembolización transarterial con esferas de itrio-90 (TARE) en pacientes con metástasis hepáticas de cáncer colorrectal. Material y métodos: Estudio prospectivo que incluye los pacientes con metástasis hepáticas de cancer colorrectal tratados con TARE entre noviembre de 2015 y junio de 2020. Se analizó la respuesta terapéutica (3 y 6 meses, criterios RECIST v1.1) mediante el cálculo de las tasas de respuesta tumoral objetiva (ORR) y de control de la enfermedad (DCR), así como la asociación de los biomarcadores con la respuesta terapéutica y la supervivencia global (SG) y libre de progresión (SLP). Resultados: Treinta TARE en 23 pacientes (edad media 61,61±9,13 años; 56,5% varones). La ORR a los 3 meses fue del 16,7% y el DCR del 53,3%. A los 6 meses progresaron el 80% de los pacientes. La ORR y DCR se asociaron con la edad (p=0,047), tratamiento con bevacizumab (p=0,008), hemoglobina (p=0,008), NLR (p=0,040), albúmina (p=0,012) y GPT (p=0,023) previas a la TARE, y la dosis absorbida tumoral estimada>115Gy (p=0,033). La mediana de SG fue de 12 meses (IC 95%: 4,75-19,25 meses) y de SLP 3 meses (IC 95%: 2,41-3,59 meses). La SG se asoció con la cirugía del tumor primario (p=0,019), mutación KRAS (p=0,024), hemoglobina (p=0,009), NLR (p=0,005) y PLR (p=0,042) previos a la TARE. Conclusión: Los biomarcadores con capacidad para predecir el pronóstico y respuesta terapéutica a la TARE incluyen desde parámetros bioquímicos a factores relacionados con la dosimetría tumoral estimada (AU)
Objetivo: To determine the therapeutic effectiveness and safety of transarterial radioembolization (TARE) with Yttrium-90 in patients with colorectal cancer (CRC) liver metastases and to evaluate the prognostic value of different biomarkers. Material and methods: This prospective longitudinal study enrolled consecutive patients with CRC liver metastases treated with TARE between November 2015 and june 2020. The therapeutic response at three and six months (RECIST1.1 criteria) and the relationship of biomarkers with therapeutic response, by calculating objective tumor response rates (ORR) and disease control (DCR), and overall survival (OS) and progression-free (PFS). Results: Thirty TAREs were performed in 23 patients (mean age, 61,61±9,13 years; 56,5% male). At three months, the objective response rate (ORR) was 16,7% and the disease control rate (DCR) 53,3%. At six months, the disease progressed in 80%. The ORR and DCR were significantly associated with age at diagnosis (P=.047), previous bevacizumab treatment (P=.008), pre-TARE haemoglobin (P=.008), NLR (P=.040), pre-TARE albumin (P=.012), pre-TARE ALT (P=.023) and tumour-absorbed dose>115Gy (P=.033). Median overall survival (OS) was 12 months (95% CI, 4.75-19.25 months) and median progression-free survival (PFS) 3 months (95% CI, 2.41-3.59). OS was significantly associated with primary tumour resection (P=.019), KRAS mutation (HR: 5.15; P=.024), pre-TARE haemoglobin (HR: .50; p=.009), pre-TARE NLR (HR: 1.65; P=.005) and PLR (HR: 1.01; P=.042). Conclusion: TARE prognosis and therapeutic response were predicted by different biomarkers, ranging from biochemical parameters to tumour dosimetrics (AU)
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Humanos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Neoplasias Colorrectales/patología , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/radioterapia , Radioisótopos de Itrio/administración & dosificación , Biomarcadores , Estudios Longitudinales , Estudios Prospectivos , Radiofármacos/uso terapéutico , Radioisótopos , Pronóstico , Análisis de SupervivenciaRESUMEN
Recessive dystrophic epidermolysis bullosa (RDEB) is a genetic extracellular matrix disease caused by deficiency in type VII collagen (Col VII). The disease manifests with devastating mucocutaneous fragility leading to progressive fibrosis and metastatic squamous cell carcinomas. Although Col VII abundance is considered the main predictor of symptom course, previous studies have revealed the existence of mutation-independent mechanisms that control disease progression. Here, to investigate and validate new molecular modifiers of wound healing and fibrosis in a natural human setting, and toward development of disease-modulating treatment of RDEB, we performed gene expression profiling of primary fibroblast from RDEB siblings with marked phenotypic variations, despite having equal COL7A1 genotype. Gene enrichment analysis suggested that severe RDEB was associated with enhanced response to TGF-ß stimulus, oxidoreductase activity, and cell contraction. Consistently, we found an increased response to TGF-ß, higher levels of basal and induced reactive oxygen species (ROS), and greater contractile ability in collagen lattices in RDEB fibroblasts (RDEBFs) from donors with severe RDEB vs mild RDEB. Treatment with antioxidants allowed a reduction of the pro-fibrotic and contractile phenotype. Importantly, our analyses revealed higher expression and deposition in skin of the relatively uncharacterized small leucine-rich extracellular proteoglycan PRELP/prolargin associated with milder RDEB manifestations. Mechanistic investigations showed that PRELP effectively attenuated fibroblasts' response to TGF-ß1 stimulus and cell contractile capacity. Moreover, PRELP overexpression in RDEBFs enhanced RDEB keratinocyte attachment to fibroblast-derived extracellular matrix in the absence of Col VII. Our results highlight the clinical relevance of pro-oxidant status and hyper-responsiveness to TGF-ß in RDEB severity and progression. Of note, our study also reveals PRELP as a novel and natural TGF-ß antagonist with a likely dermo-epidermal pro-adhesive capacity.
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Epidermólisis Ampollosa Distrófica , Colágeno Tipo VII/genética , Epidermólisis Ampollosa Distrófica/genética , Proteínas de la Matriz Extracelular/genética , Fibroblastos/metabolismo , Fibrosis , Glicoproteínas , Humanos , Mutación , Proteoglicanos Pequeños Ricos en Leucina/genética , Factor de Crecimiento Transformador beta/genética , Factor de Crecimiento Transformador beta/metabolismoRESUMEN
Neuroleptic malignant syndrome is a rare medical emergency associated with the use of antipsychotics and other antidopaminergic drugs. There is no specific test, and diagnosis is based on high clinical suspicion and good differential diagnosis. A clinical picture consistent with hyperthermia, muscle rigidity, altered level of consciousness, together with signs of rhabdomyolysis in analytical studies and a history of taking neuroleptic drugs are the key elements in the detection of this entity. Due to its low incidence and potential mortality, it is essential to publish case reports of neuroleptic malignant syndrome in order to raise awareness of this entity and facilitate diagnostic suspicion when encountering a patient with compatible symptoms. The following is the case of a 79 year old patient with chronic alcohol consumption as the only history of interest, who was given a single dose of haloperidol after an episode of delirium in the postoperative period of conventional trauma surgery. She subsequently developed a picture of progressive deterioration of the level of consciousness, diaphoresis, generalized muscle rigidity, hyperthermia, together with severe metabolic acidosis, hyperlacticaemia, rhabdomyolysis, hypertransaminasemia and hypocalcemia. After ruling out other entities compatible with the clinical picture, neuroleptic malignant syndrome was given as the main diagnostic hypothesis. Diagnosis was confirmed after clinical and analytical improvement following treatment with dantrolene. The patient was discharged from hospital with no sequelae a few days after onset of the condition.
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Antipsicóticos , Síndrome Neuroléptico Maligno , Rabdomiólisis , Anciano , Antipsicóticos/efectos adversos , Femenino , Fiebre , Humanos , Rigidez Muscular/complicaciones , Rigidez Muscular/tratamiento farmacológico , Síndrome Neuroléptico Maligno/complicaciones , Síndrome Neuroléptico Maligno/etiología , Periodo Posoperatorio , Rabdomiólisis/inducido químicamente , Rabdomiólisis/complicacionesRESUMEN
INTRODUCTION: It has been observed in recent years that levels of such molecules as calcitonin gene-related peptide (CGRP) and, to a lesser extent, the pituitary adenylate cyclase-activating peptide are elevated during migraine attacks and in chronic migraine, both in the cerebrospinal fluid and in the serum. Pharmacological reduction of these proteins is clinically significant, with an improvement in patients' migraines. It therefore seems logical that one of the main lines of migraine research should be based on the role of CGRP in the pathophysiology of this entity. DEVELOPMENT: The Spanish Society of Neurology's Headache Study Group decided to draft this document in order to address the evidence on such important issues as the role of CGRP in the pathophysiology of migraine and the mechanism of action of monoclonal antibodies and gepants; and to critically analyse the results of different studies and the profile of patients eligible for treatment with monoclonal antibodies, and the impact in terms of pharmacoeconomics. CONCLUSIONS: The clinical development of gepants, which are CGRP antagonists, for the acute treatment of migraine attacks, and CGRP ligand and receptor monoclonal antibodies offer promising results for these patients.
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Péptido Relacionado con Gen de Calcitonina , Trastornos Migrañosos , Anticuerpos Monoclonales/uso terapéutico , Péptido Relacionado con Gen de Calcitonina/metabolismo , Antagonistas del Receptor Peptídico Relacionado con el Gen de la Calcitonina/uso terapéutico , Cefalea/tratamiento farmacológico , Humanos , Trastornos Migrañosos/tratamiento farmacológicoRESUMEN
El síndrome neuroléptico maligno es una emergencia médica poco frecuente asociada al uso de antipsicóticos y otros fármacos antidopaminérgicos. No se dispone de una prueba específica para su diagnóstico, basándose este en una alta sospecha clínica y la realización de un buen diagnóstico diferencial. Un cuadro clínico compatible, destacando la hipertermia, rigidez muscular, alteración del nivel de conciencia y signos de rabdomiolisis en los estudios analíticos, junto con el antecedente de la toma de fármacos neurolépticos, constituyen los elementos clave para la detección de esta entidad. Debido a su escasa incidencia y su potencial mortalidad, es primordial su conocimiento a través de series de casos descritos en la literatura para facilitar su sospecha diagnóstica ante un caso clínico compatible. A continuación, exponemos un caso de una paciente de 79 años con consumo crónico de alcohol como único antecedente de interés, que recibió una dosis única de haloperidol tras un cuadro de delirio en el contexto de un postoperatorio convencional de traumatología. Posteriormente, desarrolló un cuadro de deterioro progresivo del nivel de conciencia, diaforesis, rigidez muscular generalizada, hipertermia, junto a acidosis metabólica severa, hiperlactacidemia, rabdomiolisis, hipertransaminasemia e hipocalcemia. Tras excluir otras entidades compatibles con la clínica, el síndrome neuroléptico maligno se postuló como la principal hipótesis diagnóstica, reforzándose el diagnóstico tras la mejoría clínica y analítica evidente posterior al inicio del tratamiento con dantrolene. La paciente pudo, finalmente, ser dada de alta escasos días después del inicio del cuadro sin presentar secuelas.(AU)
Neuroleptic malignant syndrome is a rare medical emergency associated with the use of antipsychotics and other antidopaminergic drugs. There is no specific test, and diagnosis is based on high clinical suspicion and good differential diagnosis.A clinical picture consistent with hyperthermia, muscle rigidity, altered level of consciousness, together with signs of rhabdomyolysis in analytical studies and a history of taking neuroleptic drugs are the key elements in the detection of this entity.Due to its low incidence and potential mortality, it is essential to publish case reports of neuroleptic malignant syndrome in order to raise awareness of this entity and facilitate diagnostic suspicion when encountering a patient with compatible symptoms.The following is the case of a 79 year old patient with chronic alcohol consumption as the only history of interest, who was given a single dose of haloperidol after an episode of delirium in the postoperative period of conventional trauma surgery. She subsequently developed a picture of progressive deterioration of the level of consciousness, diaphoresis, generalized muscle rigidity, hyperthermia, together with severe metabolic acidosis, hyperlacticaemia, rhabdomyolysis, hypertransaminasemia and hypocalcemia. After ruling out other entities compatible with the clinical picture, neuroleptic malignant syndrome was given as the main diagnostic hypothesis. Diagnosis was confirmed after clinical and analytical improvement following treatment with dantrolene. The patient was discharged from hospital with no sequelae a few days after onset of the condition.(AU)
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Humanos , Femenino , Anciano , Síndrome Neuroléptico Maligno , Periodo Posoperatorio , Síndrome Neuroléptico Maligno/diagnóstico , Antipsicóticos , Síndrome Neuroléptico Maligno/tratamiento farmacológico , Síndrome Neuroléptico Maligno/mortalidad , Pacientes Internos , Atención al PacienteRESUMEN
Although many more eyes of children with retinoblastoma are salvaged now compared to just 10 years ago, the control of vitreous seeding remains a challenge. The introduction of intravitreal injection of melphalan has enabled more eyes to be salvaged safely but with definite retinal toxicity. Intensive treatment with high-dose intravitreal topotecan may be a strategy to control tumor burden because of its cell cycle-dependent cytotoxicity and the proven safety in humans. Therefore, we evaluated the ocular and systemic safety of repeated high-dose intravitreal injections of topotecan in rabbits. Systemic and ocular toxicity was assessed in non-tumor-bearing rabbits after four weekly injections of three doses of topotecan (10 µg, 25 µg, and 50 µg) or vehicle alone. Animals were evaluated weekly for general and ophthalmic clinical status. One week after the last injection, vitreous and plasma samples were collected for drug quantification and the enucleated eyes were subjected to histological assessment. Weight, hair loss, or changes in hematologic values were absent during the study period across all animal groups. Eyes injected with all topotecan doses or vehicle showed no signs of anterior segment inflammation, clinical or histologic evidence of damage to the retina, and ERG parameters remained unaltered throughout the study. Vitreous and plasma topotecan lactone concentrations were undetectable. Four weekly intravitreal injections of topotecan up to 50 µg in the animal model or a 100 µg human equivalent dose were not toxic for the rabbit eye. High doses of topotecan may show promising translation to the clinic for the management of difficult-to-treat retinoblastoma vitreous seeds.