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2.
Euro Surveill ; 29(14)2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38577802

RESUMEN

Elizabethkingia anophelis is a multidrug-resistant pathogen causing high mortality and morbidity in adults with comorbidities and neonates. We report a Dutch case of E. anophelis meningitis in a neonate, clonally related to samples taken from an automated infant milk dispenser located at the family's residence. We inform about the emergence of E. anophelis and suggest molecular surveillance in hospitals and other health settings. This is the first case connecting an automated formula dispenser to an invasive infection in a neonate.


Asunto(s)
Infecciones por Flavobacteriaceae , Flavobacteriaceae , Meningitis , Humanos , Recién Nacido , Infecciones por Flavobacteriaceae/diagnóstico , Infecciones por Flavobacteriaceae/tratamiento farmacológico , Infecciones por Flavobacteriaceae/epidemiología , Genoma Bacteriano , Leche , Países Bajos
3.
Front Pediatr ; 12: 1367337, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38464893

RESUMEN

Objectives: To describe the use and outcomes of the neurological wake-up test (NWT) in pediatric severe traumatic brain injury (pTBI). Design: Retrospective single-center observational cohort study. Setting: Medical-surgical tertiary pediatric intensive care unit (PICU) in a university medical center and Level 1 Trauma Center. Patients: Children younger than 18 years with severe TBI [i.e., Glasgow Coma Scale (GCS) of ≤8] admitted between January 2010 and December 2020. Subjects with non-traumatic brain injury were excluded. Measurements and main results: Of 168 TBI patients admitted, 36 (21%) met the inclusion criteria. Median age was 8.5 years [2 months to 16 years], 5 patients were younger than 6 months. Median initial Glasgow Coma Scale (GCS) and Glasgow Motor Scale (GMS) was 6 [3-8] and 3 [1-5]. NWTs were initiated in 14 (39%) patients, with 7 (50%) labelled as successful. Fall from a height was the underlying injury mechanism in those seven. NWT-failure occurred in patients admitted after traffic accidents. Sedation use in both NWT-subgroups (successful vs. failure) was comparable. Cause of NWT-failure was non-arousal (71%) or severe agitation (29%). Subjects with NWT failure subsequently had radiological examination (29%), repeat NWT (43%), continuous interruption of sedation (14%) or intracranial pressure (ICP) monitoring (14%). The primary reason for not doing NWTs was intracranial hypertension in 59%. Compared to the NWT-group, the non-NWT group had a higher PRISM III score (18.9 vs. 10.6), lower GCS/GMS at discharge, more associated trauma, and circulatory support. Nine patients (25%) died during their PICU admission, none of them had an NWT. Conclusion: We observed limited use of NWTs in pediatric severe TBI. Patients who failed the NWT were indistinguishable from those without NWT. Both groups were more severely affected compared to the NWT successes. Therefore, our results may indicate that only a select group of severe pTBI patients qualify for the NWT.

4.
Eur J Neurol ; 30(8): 2430-2441, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37170790

RESUMEN

BACKGROUND AND PURPOSE: Acute flaccid myelitis (AFM) and transverse myelitis (TM) are serious conditions that may be difficult to differentiate, especially at onset of disease. In this study, we compared clinical features of pediatric AFM and TM and evaluated current diagnostic criteria, aiming to improve early and accurate diagnosis. METHODS: Two cohorts of children with enterovirus D68-associated AFM and clinically diagnosed TM were compared regarding presenting clinical features, additional investigations, and outcome. Current diagnostic criteria for AFM and TM were applied to evaluate their specificity. RESULTS: Children with AFM (n = 21) compared to those with TM (n = 36) were younger (median 3 vs. 10 years), more often had a prodromal illness (100% vs. 39%), predominant proximal weakness (69% vs. 17%), and hyporeflexia (100% vs. 44%), and less often had sensory deficits (0% vs. 81%), bowel and/or bladder dysfunction (12% vs. 69%), and hyperreflexia (0% vs. 44%). On magnetic resonance imaging, brainstem involvement was more common in AFM (74% vs. 21%), whereas supratentorial abnormalities were only seen in TM (0% vs. 40%). When omitting the criterion of a sensory level, 11 of 15 (73%) children with AFM fulfilled the diagnostic criteria for TM. Of children with TM, four of 33 (12%) fulfilled the diagnostic criteria for probable/definite AFM. CONCLUSIONS: Although there is considerable overlap between AFM and TM in children, we found important early differentiating clinical and diagnostic features. Meeting diagnostic criteria for AFM in children with TM and vice versa underlines the importance of thorough clinical examination and early and accurate diagnostic studies.


Asunto(s)
Enfermedades Virales del Sistema Nervioso Central , Infecciones por Enterovirus , Mielitis Transversa , Mielitis , Enfermedades Neuromusculares , Niño , Humanos , Mielitis Transversa/diagnóstico , Infecciones por Enterovirus/complicaciones , Infecciones por Enterovirus/diagnóstico , Enfermedades Neuromusculares/diagnóstico , Mielitis/diagnóstico , Enfermedades Virales del Sistema Nervioso Central/diagnóstico , Enfermedades Virales del Sistema Nervioso Central/complicaciones
5.
Eur J Paediatr Neurol ; 44: 28-36, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-36996587

RESUMEN

BACKGROUND: Acute flaccid paralysis (AFP) is characterized by rapidly progressive limb weakness with low muscle tone. It has a broad differential diagnosis, which includes acute flaccid myelitis (AFM), a rare polio-like condition that mainly affects young children. Differentiation between AFM and other causes of AFP may be difficult, particularly at onset of disease. Here, we evaluate the diagnostic criteria for AFM and compare AFM to other causes of acute weakness in children, aiming to identify differentiating clinical and diagnostic features. METHODS: The diagnostic criteria for AFM were applied to a cohort of children with acute onset of limb weakness. An initial classification based on positive diagnostic criteria was compared to the final classification, based on application of features suggestive for an alternative diagnosis and discussion with expert neurologists. Cases classified as definite, probable, or possible AFM or uncertain, were compared to cases with an alternative diagnosis. RESULTS: Of 141 patients, seven out of nine patients initially classified as definite AFM, retained this label after further classification. For probable AFM, this was 3/11, for possible AFM 3/14 and for uncertain 11/43. Patients initially classified as probable or possible AFM were most commonly diagnosed with transverse myelitis (16/25). If the initial classification was uncertain, Guillain-Barré syndrome was the most common diagnosis (31/43). Clinical and diagnostic features not included in the diagnostic criteria, were often used for the final classification. CONCLUSION: The current diagnostic criteria for AFM usually perform well, but additional features are sometimes required to distinguish AFM from other conditions.


Asunto(s)
Enterovirus Humano D , Infecciones por Enterovirus , Mielitis Transversa , Enfermedades Neuromusculares , Niño , Humanos , Preescolar , alfa-Fetoproteínas , Infecciones por Enterovirus/diagnóstico , Enfermedades Neuromusculares/diagnóstico , Enfermedades Neuromusculares/complicaciones , Mielitis Transversa/diagnóstico , Debilidad Muscular , Parálisis/diagnóstico , Parálisis/etiología
6.
Euro Surveill ; 27(42)2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-36268734

RESUMEN

BackgroundAcute flaccid myelitis (AFM) is a polio-like condition affecting mainly children and involving the central nervous system (CNS). AFM has been associated with different non-polio-enteroviruses (EVs), in particular EV-D68 and EV-A71. Reliable incidence rates in European countries are not available.AimTo report AFM incidence in children in the Netherlands and its occurrence relative to EV-D68 and EV-A71 detections.MethodsIn 10 Dutch hospitals, we reviewed electronic health records of patients diagnosed with a clinical syndrome including limb weakness and/or CNS infection and who were < 18 years old when symptoms started. After excluding those with a clear alternative diagnosis to AFM, those without weakness, and removing duplicate records, only patients diagnosed in January 2014-December 2019 were retained and further classified according to current diagnostic criteria. Incidence rates were based on definite and probable AFM cases. Cases' occurrences during the study period were co-examined with laboratory-surveillance detections of EV-D68 and EV-A71.ResultsAmong 143 patients included, eight were classified as definite and three as probable AFM. AFM mean incidence rate was 0.06/100,000 children/year (95% CI: -0.03 to 0.14). All patient samples were negative for EV-A71. Of respiratory samples in seven patients, five were EV-D68 positive. AFM cases clustered in periods with increased EV-D68 and EV-A71 detections.ConclusionsAFM is rare in children in the Netherlands. The temporal coincidence of EV-D68 circulation and AFM and the detection of this virus in several cases' samples support its association with AFM. Increased AFM awareness among clinicians, adequate diagnostics and case registration matter to monitor the incidence.


Asunto(s)
Enfermedades Virales del Sistema Nervioso Central , Enterovirus Humano A , Enterovirus Humano D , Infecciones por Enterovirus , Mielitis , Poliomielitis , Humanos , Niño , Adolescente , Países Bajos/epidemiología , Mielitis/diagnóstico , Mielitis/epidemiología , Enfermedades Virales del Sistema Nervioso Central/diagnóstico , Enfermedades Virales del Sistema Nervioso Central/epidemiología , Infecciones por Enterovirus/diagnóstico , Infecciones por Enterovirus/epidemiología
7.
Eur J Neurol ; 29(2): 593-604, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-34747551

RESUMEN

BACKGROUND AND PURPOSE: Differentiation between acute flaccid myelitis (AFM) and Guillain-Barré syndrome (GBS) can be difficult, particularly in children. Our objective was to improve the diagnostic accuracy by giving recommendations based on a comparison of clinical features and diagnostic criteria in children with AFM or GBS. METHODS: A cohort of 26 children with AFM associated with enterovirus D68 was compared to a cohort of 156 children with GBS. The specificity of the Brighton criteria, used for GBS diagnosis, was evaluated in the AFM cohort and the specificity of the Centers for Disease Control and Prevention (CDC) AFM diagnostic criteria in the GBS cohort. RESULTS: Children with AFM compared to those with GBS had a shorter interval between onset of weakness and nadir (3 vs. 8 days, p < 0.001), more often had asymmetric limb weakness (58% vs. 0%, p < 0.001), and less frequently had sensory deficits (0% vs. 40%, p < 0.001). In AFM, cerebrospinal fluid leukocyte counts were higher, whereas protein concentrations were lower. Spinal cord lesions on magnetic resonance imaging were only found in AFM patients. No GBS case fulfilled CDC criteria for definite AFM. Of the AFM cases, 8% fulfilled the Brighton criteria for GBS, when omitting the criterion of excluding an alternate diagnosis. CONCLUSIONS: Despite the overlap in clinical presentation, we found distinctive early clinical and diagnostic characteristics for differentiating AFM from GBS in children. Diagnostic criteria for AFM and GBS usually perform well, but some AFM cases may fulfill clinical diagnostic criteria for GBS. This underlines the need to perform diagnostic tests early to exclude AFM in children suspected of atypical GBS.


Asunto(s)
Enfermedades Virales del Sistema Nervioso Central , Síndrome de Guillain-Barré , Mielitis , Enfermedades Neuromusculares , Enfermedades Virales del Sistema Nervioso Central/complicaciones , Enfermedades Virales del Sistema Nervioso Central/diagnóstico , Niño , Síndrome de Guillain-Barré/complicaciones , Síndrome de Guillain-Barré/diagnóstico , Humanos , Mielitis/diagnóstico , Enfermedades Neuromusculares/complicaciones , Enfermedades Neuromusculares/diagnóstico
8.
Brain Dev ; 43(5): 626-636, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33509615

RESUMEN

OBJECTIVE: It may be difficult for clinicians to estimate the prognosis of pediatric acute transverse myelitis (ATM). The aim of this study was to define prognostic factors for relapsing disease and poor outcome in pediatric ATM. METHODS: This prospective cohort study included 49 children, 18 boys and 31 girls (median age 13.1 years, IQR 6.5-16.2) with a first episode of ATM. Factors associated with relapsing disease and poor outcome (Expanded Disability Status Scale (EDSS) ≥ 4) were assessed during a median follow-up of 37 months (IQR 18-75). RESULTS: In total, 14 patients (29%) experienced ≥ 1 relapse(s) and nine patients (18%) had a poor outcome. Factors at onset associated with relapsing disease included higher age (16.1 vs. 11.6 years, p = 0.002), longer time to maximum severity of symptoms (5.5 vs. 3 days, p = 0.01), lower maximum EDSS score (4.0 vs. 6.5, p = 0.003), short lesion on spinal MRI (64 vs. 21%, p = 0.006), abnormalities on brain MRI (93 vs. 44%, p = 0.002) and presence of oligoclonal bands in cerebrospinal fluid (67 vs. 14%, p = 0.004). The only factor associated with poor outcome was presence of a spinal cord lesion on MRI without cervical involvement (56 vs. 14%, p = 0.02). CONCLUSION: Pediatric ATM patients presenting with clinical, radiological and laboratory features associated with multiple sclerosis (MS) are at risk for relapsing disease. In absence of these known MS risk factors at onset of disease these patients are at low risk for relapses. Only a minority of pediatric ATM patients in this cohort have a poor outcome.


Asunto(s)
Esclerosis Múltiple/diagnóstico , Mielitis Transversa/diagnóstico , Enfermedad Aguda , Adolescente , Niño , Preescolar , Femenino , Estudios de Seguimiento , Humanos , Masculino , Esclerosis Múltiple/metabolismo , Esclerosis Múltiple/patología , Esclerosis Múltiple/fisiopatología , Mielitis Transversa/metabolismo , Mielitis Transversa/patología , Mielitis Transversa/fisiopatología , Neuromielitis Óptica/diagnóstico , Neuromielitis Óptica/metabolismo , Neuromielitis Óptica/patología , Neuromielitis Óptica/fisiopatología , Evaluación de Resultado en la Atención de Salud , Pronóstico , Recurrencia
9.
Lancet ; 397(10271): 334-346, 2021 01 23.
Artículo en Inglés | MEDLINE | ID: mdl-33357469

RESUMEN

Acute flaccid myelitis (AFM) is a disabling, polio-like illness mainly affecting children. Outbreaks of AFM have occurred across multiple global regions since 2012, and the disease appears to be caused by non-polio enterovirus infection, posing a major public health challenge. The clinical presentation of flaccid and often profound muscle weakness (which can invoke respiratory failure and other critical complications) can mimic several other acute neurological illnesses. There is no single sensitive and specific test for AFM, and the diagnosis relies on identification of several important clinical, neuroimaging, and cerebrospinal fluid characteristics. Following the acute phase of AFM, patients typically have substantial residual disability and unique long-term rehabilitation needs. In this Review we describe the epidemiology, clinical features, course, and outcomes of AFM to help to guide diagnosis, management, and rehabilitation. Future research directions include further studies evaluating host and pathogen factors, including investigations into genetic, viral, and immunological features of affected patients, host-virus interactions, and investigations of targeted therapeutic approaches to improve the long-term outcomes in this population.


Asunto(s)
Enfermedades Virales del Sistema Nervioso Central/diagnóstico por imagen , Enfermedades Virales del Sistema Nervioso Central/rehabilitación , Infecciones por Enterovirus/epidemiología , Hipotonía Muscular , Debilidad Muscular , Mielitis/diagnóstico por imagen , Mielitis/rehabilitación , Enfermedades Neuromusculares/diagnóstico por imagen , Enfermedades Neuromusculares/rehabilitación , Enfermedades Virales del Sistema Nervioso Central/líquido cefalorraquídeo , Enfermedades Virales del Sistema Nervioso Central/virología , Niño , Infecciones por Enterovirus/líquido cefalorraquídeo , Infecciones por Enterovirus/complicaciones , Salud Global , Humanos , Imagen por Resonancia Magnética , Hipotonía Muscular/etiología , Debilidad Muscular/etiología , Mielitis/líquido cefalorraquídeo , Mielitis/virología , Enfermedades Neuromusculares/líquido cefalorraquídeo , Enfermedades Neuromusculares/virología , Evaluación del Resultado de la Atención al Paciente
10.
Eur J Pediatr ; 178(9): 1305-1315, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31338675

RESUMEN

Acute flaccid myelitis is characterized by the combination of acute flaccid paralysis and a spinal cord lesion largely restricted to the gray matter on magnetic resonance imaging. The term acute flaccid myelitis was introduced in 2014 after the upsurge of pediatric cases in the USA with enterovirus D68 infection. Since then, an increasing number of cases have been reported worldwide. Whereas the terminology is new, the clinical syndrome has been recognized in the past in association with several other neurotropic viruses such as poliovirus.Conclusion: This review presents the current knowledge on acute flaccid myelitis with respect to the clinical presentation and its differential diagnosis with Guillain-Barré syndrome and acute transverse myelitis. We also discuss the association with enterovirus D68 and the presumed pathophysiological mechanism of this infection causing anterior horn cell damage. Sharing clinical knowledge and insights from basic research is needed to make progress in diagnosis, treatment, and prevention of this new polio-like disease. What is Known: • Acute flaccid myelitis (AFM) is a polio-like condition characterized by rapid progressive asymmetric weakness, together with specific findings on MRI • AFM has been related to different viral agents, but recent outbreaks are predominantly associated with enterovirus D68. What is New: • Improving knowledge on AFM must increase early recognition and adequate diagnostic procedures by clinicians. • The increasing incidence of AFM urges cooperation between pediatricians, neurologists, and microbiologists for the development of treatment and preventive options.


Asunto(s)
Enfermedades Virales del Sistema Nervioso Central/diagnóstico , Enterovirus Humano D , Infecciones por Enterovirus/diagnóstico , Mielitis/diagnóstico , Enfermedades Neuromusculares/diagnóstico , Enfermedades Virales del Sistema Nervioso Central/epidemiología , Enfermedades Virales del Sistema Nervioso Central/terapia , Enfermedades Virales del Sistema Nervioso Central/virología , Diagnóstico Diferencial , Infecciones por Enterovirus/complicaciones , Infecciones por Enterovirus/epidemiología , Infecciones por Enterovirus/terapia , Salud Global , Síndrome de Guillain-Barré/diagnóstico , Síndrome de Guillain-Barré/virología , Humanos , Mielitis/epidemiología , Mielitis/terapia , Mielitis/virología , Mielitis Transversa/diagnóstico , Mielitis Transversa/virología , Enfermedades Neuromusculares/epidemiología , Enfermedades Neuromusculares/terapia , Enfermedades Neuromusculares/virología , Pronóstico
11.
Pediatr Infect Dis J ; 38(1): 16-21, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-30234793

RESUMEN

BACKGROUND: Enterovirus-D68 (EV-D68) is a respiratory virus within the genus Enterovirus and the family of Picornaviridae. Genetically, it is closely related to rhinovirus that replicates in the respiratory tract and causes respiratory disease. Since 2014, EV-D68 has been associated with the neurologic syndrome of acute flaccid myelitis (AFM). METHODS: In October 2016, questionnaires were sent out to a European network including 66 virologists and clinicians, to develop an inventory of EV-D68-associated AFM cases in Europe. Clinical and virologic information of case patients was requested. In addition, epidemiologic information on EV testing was collected for the period between March and October 2016. RESULTS: Twenty-nine cases of EV-D68-associated AFM were identified, from 12 different European countries. Five originated from France, 5 from Scotland and 3 each from Sweden, Norway and Spain. Twenty-six were children (median age 3.8 years), 3 were adults. EV-D68 was detected in respiratory materials (n = 27), feces (n = 8) and/or cerebrospinal fluid (n = 2). Common clinical features were asymmetric flaccid limb weakness, cranial nerve deficits and bulbar symptoms. On magnetic resonance imaging, typical findings were hyperintensity of the central cord and/or brainstem; low motor amplitudes with normal conduction velocities were seen on electromyography. Full clinical recovery was rare (n = 3), and 2 patients died. The epidemiologic data from 16 European laboratories showed that of all EV-D68-positive samples, 99% was detected in a respiratory specimen. CONCLUSIONS: For 2016, 29 EV-D68-related AFM cases were identified in mostly Western Europe. This is likely an underestimation, because case identification is dependent on awareness among clinicians, adequate viral diagnostics on respiratory samples and the capability of laboratories to type EVs.


Asunto(s)
Enfermedades Virales del Sistema Nervioso Central/virología , Infecciones por Enterovirus/complicaciones , Infecciones por Enterovirus/epidemiología , Mielitis/virología , Enfermedades Neuromusculares/virología , Adolescente , Adulto , Enfermedades Virales del Sistema Nervioso Central/epidemiología , Niño , Preescolar , Brotes de Enfermedades/estadística & datos numéricos , Enterovirus Humano D/patogenicidad , Infecciones por Enterovirus/líquido cefalorraquídeo , Europa (Continente)/epidemiología , Heces/virología , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Hipotonía Muscular/virología , Mielitis/epidemiología , Enfermedades Neuromusculares/epidemiología , Parálisis/virología , Sistema Respiratorio/virología , Encuestas y Cuestionarios , Adulto Joven
13.
Crit Rev Oncol Hematol ; 104: 30-41, 2016 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-27263935

RESUMEN

Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder, associated with a variable clinical phenotype including café-au-lait spots, intertriginous freckling, Lisch nodules, neurofibromas, optic pathway gliomas and distinctive bony lesions. NF1 is caused by a mutation in the NF1 gene, which codes for neurofibromin, a large protein involved in the MAPK- and the mTOR-pathway through RAS-RAF signalling. NF1 is a known tumour predisposition syndrome, associated with different tumours of the nervous system including low grade gliomas (LGGs) in the paediatric population. The focus of this review is on grade I pilocytic astrocytomas (PAs), the most commonly observed histologic subtype of low grade gliomas in NF1. Clinically, these PAs have a better prognosis and show different localisation patterns than their sporadic counterparts, which are most commonly associated with a KIAA1549:BRAF fusion. In this review, possible mechanisms of tumourigenesis in LGGs with and without NF1 will be discussed, including the contribution of different signalling pathways and tumour microenvironment. Furthermore we will discuss how increased understanding of tumourigenesis may lead to new potential targets for treatment.


Asunto(s)
Glioma/etiología , Neurofibromatosis 1/complicaciones , Animales , Glioma/diagnóstico , Humanos , Mutación , Clasificación del Tumor , Fenotipo , Transducción de Señal , Microambiente Tumoral
14.
Sci Transl Med ; 5(182): 182ra53, 2013 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-23616120

RESUMEN

A rare neurodevelopmental disorder in the Old Order Mennonite population called PMSE (polyhydramnios, megalencephaly, and symptomatic epilepsy syndrome; also called Pretzel syndrome) is characterized by infantile-onset epilepsy, neurocognitive delay, craniofacial dysmorphism, and histopathological evidence of heterotopic neurons in subcortical white matter and subependymal regions. PMSE is caused by a homozygous deletion of exons 9 to 13 of the LYK5/STRADA gene, which encodes the pseudokinase STRADA, an upstream inhibitor of mammalian target of rapamycin complex 1 (mTORC1). We show that disrupted pathfinding in migrating mouse neural progenitor cells in vitro caused by STRADA depletion is prevented by mTORC1 inhibition with rapamycin or inhibition of its downstream effector p70 S6 kinase (p70S6K) with the drug PF-4708671 (p70S6Ki). We demonstrate that rapamycin can rescue aberrant cortical lamination and heterotopia associated with STRADA depletion in the mouse cerebral cortex. Constitutive mTORC1 signaling and a migration defect observed in fibroblasts from patients with PMSE were also prevented by mTORC1 inhibition. On the basis of these preclinical findings, we treated five PMSE patients with sirolimus (rapamycin) without complication and observed a reduction in seizure frequency and an improvement in receptive language. Our findings demonstrate a mechanistic link between STRADA loss and mTORC1 hyperactivity in PMSE, and suggest that mTORC1 inhibition may be a potential treatment for PMSE as well as other mTOR-associated neurodevelopmental disorders.


Asunto(s)
Enfermedades del Sistema Nervioso Central/tratamiento farmacológico , Enfermedades del Sistema Nervioso Central/metabolismo , Convulsiones/tratamiento farmacológico , Sirolimus/uso terapéutico , Animales , Western Blotting , Movimiento Celular/efectos de los fármacos , Células Cultivadas , Citarabina/farmacología , Femenino , Humanos , Imidazoles/farmacología , Inmunohistoquímica , Diana Mecanicista del Complejo 1 de la Rapamicina , Ratones , Complejos Multiproteicos/metabolismo , Piperazinas/farmacología , Embarazo , Serina-Treonina Quinasas TOR/metabolismo
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