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Several studies suggest that crack cocaine users exhibit higher prevalence of both psychiatric and psychosocial problems, with an aggressive pattern of drug use. Nevertheless, few experimental studies attempted to verify the neurotoxicity after crack cocaine exposure, especially when compared with other routes of cocaine administration. This systematic review aimed to verify whether in vitro and/or in vivo crack cocaine exposure is more neurotoxic than cocaine exposure (snorted or injected). A search was performed in the PubMed, EMBASE, Scopus, Web of Science, and LILACS databases for in vitro and in vivo toxicological studies conducted with either rats or mice, with no distinction with regard to sex or age. Other methods including BioRxiv, BDTD, Academic Google, citation searching, and specialist consultation were also adopted. Two independent investigators screened the titles and abstracts of retrieved studies and subsequently performed full-text reading and data extraction. The quality of the included studies was assessed by the Toxicological data Reliability assessment Tool (ToxRTool). The study protocol was registered with the Prospective Registry of Systematic Reviews (PROSPERO; CRD42022332250). Of the twelve studies included, three were in vitro and nine were in vivo studies. According to the ToxRTool, most studies were considered reliable either with or without restrictions, with no one being considered as not reliable. The studies found neuroteratogenic effects, decreased threshold for epileptic seizures, schizophrenic-like symptoms, and cognitive deficits to be associated with crack cocaine exposure. Moreover, both in vitro and in vivo studies reported a worsening in cocaine neurotoxic effect caused by the anhydroecgonine methyl ester (AEME), a cocaine main pyrolysis product, which is in line with the more aggressive pattern of crack cocaine use. This systematic review suggests that crack cocaine exposure is more neurotoxic than other routes of cocaine administration. However, before the scarcity of studies on this topic, further toxicological studies are necessary.
Assuntos
Cocaína Crack , Síndromes Neurotóxicas , Animais , Cocaína Crack/toxicidade , Síndromes Neurotóxicas/etiologia , Humanos , Camundongos , Ratos , Transtornos Relacionados ao Uso de CocaínaRESUMO
Widespread contamination of the Amazon basin with mercury has been reported to occur since at least the mid-80s due to heavy gold mining activity. Although initial studies have indicated that this may lead to deleterious neurological consequences to the indigenous populations living in the region, further research is needed to better characterize the neurological burden of such long-term exposure. With this aim, a cross-sectional exploratory study has been conducted with the Yanomami indigenous population residing in a northern Amazon region. All participants underwent a structured interview; detailed neurological examination, including assessment for cognitive, motor, coordination, and sensory functions; and laboratorial testing for serum hemoglobin, blood glucose, and methylmercury levels in hair samples. This study enrolled 154 individuals of 30.9 ± 16.8 years of age, of which 56.1% were female. Mean methylmercury levels in hair were 3.9 ± 1.7 µg/g. Methylmercury levels in hair > 6.0 µg/g were found in 10.3%. Among participants with hair methylmercury levels ≥ 6.0 µg/g, the prevalences of peripheral neuropathy and reduced cognitive performance were, respectively, 78.8% (95%CI 15-177%, p = 0.010) and 95.9% (95%CI 16-230.8%, p = 0.012) higher than those of individuals with lower levels. These results suggest that chronic mercury exposure may lead to significant and potentially irreversible neurotoxicity to Yanomami population living in the northern Amazon basin.
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Resumen Los inhibidores del punto de control inmunitario han demostrado mejorar el pronóstico de múltiples enfer medades oncológicas. Recientemente se han reportado eventos adversos relacionados a la inmunoterapia. La to xicidad neurológica es poco frecuente. Se presenta el caso de un paciente con encefalitis relacionada con inhibido res del punto de control inmunitario.
Abstract Immune checkpoint inhibitors have been shown to improve the prognosis of multiple oncological diseases. Recently, adverse events related to immunotherapy have been reported. Neurologic toxicity is infrequent. We pre sent the case of a patient with encephalitis associated to immune checkpoint inhibitors.
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Immune checkpoint inhibitors have been shown to improve the prognosis of multiple oncological diseases. Recently, adverse events related to immunotherapy have been reported. Neurologic toxicity is infrequent. We present the case of a patient with encephalitis associated to immune checkpoint inhibitors.
Los inhibidores del punto de control inmunitario han demostrado mejorar el pronóstico de múltiples enfermedades oncológicas. Recientemente se han reportado eventos adversos relacionados a la inmunoterapia. La toxicidad neurológica es poco frecuente. Se presenta el caso de un paciente con encefalitis relacionada con inhibidores del punto de control inmunitario.
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Encefalite , Neoplasias , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Encefalite/induzido quimicamente , Imunoterapia/efeitos adversos , Prognóstico , Neoplasias/tratamento farmacológicoRESUMO
El metotrexato es un fármaco análogo del ácido fólico ampliamente utilizado en el tratamiento de enfermedades autoinmunes, leucemias y linfomas. Su uso puede ocasionar la aparición de múltiples efectos adversos entre los que se encuentran aquellos relacionados con la presencia de toxicidad neurológica, que puede presentarse de forma aguda, subaguda o crónica. La neurotoxicidad subaguda es aquella que ocurre típicamente entre los 2 y los 14 días posteriores a la administración y puede manifestarse con una amplia gama de síntomas neurológicos. En la mayoría de los casos, no recurre con futuras exposiciones al medicamento. Presentamos tres casos de neurotoxicidad subaguda por metotrexato con manifestaciones clínicas diferentes en pacientes oncohematológicos que se internaron entre los años 2018 y 2020. Dos de ellos presentaron recurrencia frente a la nueva administración del fármaco y todos evidenciaron lesiones en resonancia magnética nuclear.
Methotrexate is a folic acid analogue widely used in the treatment of autoimmune diseases, leukemias, and lymphomas. Methotrexate use may cause multiple adverse effects, including those related to the presence of neurological toxicity, which may be acute, subacute, or chronic. Subacute neurotoxicity typically occurs between 2 and 14 days after administration and may present as a wide range of neurological symptoms. In most cases, it does not recur with future exposures to the drug. Here we describe 3 cases of subacute methotrexate neurotoxicity with different clinical manifestations in patients with oncohematological disease who were hospitalized between 2018 and 2020. Two of them showed recurrence with a new drug administration. Lesions were observed in the magnetic resonance imaging tests of all of them.
Assuntos
Humanos , Masculino , Criança , Adolescente , Síndromes Neurotóxicas/etiologia , Síndromes Neurotóxicas/patologia , Síndromes Neurotóxicas/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Linfoma , Imageamento por Ressonância Magnética , Metotrexato/efeitos adversos , Antimetabólitos Antineoplásicos/efeitos adversosRESUMO
Methotrexate is a folic acid analogue widely used in the treatment of autoimmune diseases, leukemias, and lymphomas. Methotrexate use may cause multiple adverse effects, including those related to the presence of neurological toxicity, which may be acute, subacute, or chronic. Subacute neurotoxicity typically occursbetween 2 and 14 days after administration and may present as a wide range of neurological symptoms.In most cases, it does not recur with future exposures to the drug. Here we describe 3 cases of subacute methotrexate neurotoxicity with different clinical manifestations in patients with oncohematological disease who were hospitalized between 2018 and 2020. Two of them showed recurrence with a new drug administration. Lesions were observed in the magnetic resonance imaging tests of all of them.
El metotrexato es un fármaco análogo del ácido fólico ampliamente utilizado en el tratamiento de enfermedades autoinmunes, leucemias y linfomas. Su uso puede ocasionar la aparición de múltiples efectos adversos entre los que se encuentran aquellos relacionados con la presencia de toxicidad neurológica, que puede presentarse de forma aguda, subaguda o crónica. La neurotoxicidad subaguda es aquella que ocurre típicamente entre los 2 y los 14 días posteriores a la administración y puede manifestarse con una amplia gama de síntomas neurológicos. En la mayoría de los casos, no recurre con futuras exposiciones al medicamento. Presentamos tres casos de neurotoxicidad subaguda por metotrexato con manifestaciones clínicas diferentes en pacientes oncohematológicos que se internaron entre los años 2018 y 2020. Dos de ellos presentaron recurrencia frente a la nueva administración del fármaco y todos evidenciaron lesiones en resonancia magnética nuclear.
Assuntos
Linfoma , Síndromes Neurotóxicas , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Metotrexato/efeitos adversos , Antimetabólitos Antineoplásicos/efeitos adversos , Imageamento por Ressonância Magnética , Síndromes Neurotóxicas/etiologia , Síndromes Neurotóxicas/tratamento farmacológico , Síndromes Neurotóxicas/patologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológicoRESUMO
Resumo Objetivo Mapear os tipos de neurotoxicidades apresentadas por pacientes submetidos ao Transplante de Células-Tronco Hematopoéticas. Métodos Trata-se de uma Scoping Review, orientada a partir do método proposto pelo Joanna Briggs Institute, e seguiu as recomendações do Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews. A busca pelos estudos foi realizada entre os meses de julho e agosto de 2020 e ocorreu nas bases de dados e em portais de teses e dissertações nacionais e internacionais. Resultados A amostra final foi composta por 71 artigos científicos, todos na língua Inglesa. Houve destaque para o ano de 2018 com 14 (19%) publicações. Observou-se prevalência de estudos realizados nos Estados Unidos da América com 29 (40,8%). No tocante a população, todos (100%) os artigos são sobre pacientes submetidos ao transplante de células-tronco hematopoéticas que apresentaram neurotoxicidades. Acerca dos quimioterápicos utilizados no regime de condicionamento pré-transplante de células-tronco hematopoéticas sete (9,8%) utilizaram a combinação de Fludarabina e Ciclofosfamida, seguida da Ciclosporina e Tacrolimus em seis (8,4%), ciclosporina em quatro (5,6%), Fludarabina em três (4,2%). Quanto às neurotoxicidades apresentadas em pacientes submetidos ao transplante, evidenciou-se a síndrome de encefalopatia reversível posterior em 19 (26,7%) estudos. Cabe ressaltar que outros estudos identificaram essa síndrome, porém relataram sintomas diferentes. Conclusão As neurotoxicidades apresentadas por pacientes submetidos ao transplante de células-tronco hematopoéticas, são encefalopatia reversível posterior, leucoencefalopatia reversível posterior, encefalopatia de Wernicke, encefalopatia hipertensiva, encefalopatia metabólica, encefalopatia límbica, complicações hemorrágicas e convulsões.
Resumen Objetivo Mapear los tipos de neurotoxicidades en pacientes sometidos al trasplante de células madre hematopoyéticas. Métodos Se trata de una Scoping Review, orientada a partir del método propuesto por el Joanna Briggs Institute, que siguió las recomendaciones del Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews. La búsqueda de los estudios se realizó entre los meses de julio y agosto de 2020 y ocurrió en las bases de datos y en portales de tesis de doctorado y maestría nacionales e internacionales. Resultados La muestra final estuvo compuesta por 71 artículos científicos, todos en lengua inglesa. Se destacó el año 2018 con 14 publicaciones (19 %). Se observó una prevalencia de estudios realizados en Estados Unidos de América con 29 (40,8 %). En lo que se refiere a la población, todos los artículos (100 %) tratan sobre pacientes sometidos al trasplante de células madre hematopoyéticas que presentaron neurotoxicidades. Sobre los quimioterápicos utilizados en el régimen de acondicionamiento previo al trasplante de células madre hematopoyéticas, siete (9,8 %) utilizaron la combinación de Fludarabina y Ciclofosfamida, seguida de la Ciclosporina y Tacrolimus en seis (8,4 %), ciclosporina en cuatro (5,6 %), Fludarabina en tres (4,2 %). Con relación a las neurotoxicidades en pacientes sometidos al trasplante, se evidenció el síndrome de encefalopatía reversible posterior en 19 estudios (26,7 %). Cabe destacar que otros estudios identificaron ese síndrome, pero refirieron síntomas distintos. Conclusión Las neurotoxicidades presentadas por pacientes sometidos al trasplante de células madre hematopoyéticas son encefalopatía reversible posterior, leuco encefalopatía reversible posterior, encefalopatía de Wernicke, encefalopatía hipertensiva, encefalopatía metabólica, encefalopatía límbica, complicaciones hemorrágicas y convulsiones.
Abstract Objective To map the types of neurotoxicity presented by patients undergoing Hematopoietic Stem Cell Transplantation. Methods This is a scoping review, guided by the method proposed by the Joanna Briggs Institute, and followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews recommendations. The search for studies was carried out between the months of July and August 2020 and took place in databases and in national and international theses and dissertations portals. Results The final sample consisted of 71 scientific articles, all in English. There was a highlight for the year 2018 with 14 (19%) publications. There was a prevalence of studies carried out in the United States of America with 29 (40.8%). Regarding the population, all (100%) articles are about patients undergoing hematopoietic stem cell transplantation who presented neurotoxicity. Regarding the chemotherapeutic agents used in the pre-transplantation regimen of hematopoietic stem cells, seven (9.8%) used the combination of Fludarabine and Cyclophosphamide, followed by Cyclosporine and Tacrolimus in six (8.4%), Cyclosporine in four (5.6%), Fludarabine in three (4.2%). As for the neurotoxicity presented in patients undergoing transplantation, the posterior reversible encephalopathy syndrome was evidenced in 19 (26.7%) studies. It should be noted that other studies have identified this syndrome, but have reported different symptoms. Conclusion The neurotoxicity presented by patients undergoing hematopoietic stem cell transplantation are posterior reversible encephalopathy, posterior reversible leukoencephalopathy, Wernicke's encephalopathy, hypertensive encephalopathy, metabolic encephalopathy, limbic encephalopathy, hemorrhagic complications and seizures.
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La hiperbilirrubinemia es el motivo más frecuente de consulta e internación en el período neonatal. Requiere la instauración oportuna de un tratamiento eficiente, ya que los recién nacidos son especialmente vulnerables a los daños que la bilirrubina puede causar en el sistema nervioso central, debido a características propias de esta etapa de la vida.La bilirrubina en altas concentraciones produce neurotoxicidad y estrés oxidativo. Sin embargo, estudios de biología molecular demuestran que la misma molécula se comporta como un potente antioxidante.El objetivo de esta actualización es revisar cuáles son los procesos por los que la bilirrubina genera daño celular y cuáles son sus efectos antioxidantes beneficiosos. Conocer estos mecanismos facilitaría una indicación más precisa de luminoterapia individualizada, eficaz y oportuna. Hasta nuevos avances científicos, la prescripción de este tratamiento debe ser orientada por consenso de expertos
Hyperbilirubinemia is the most common reason for consultation and hospitalization in the neonatal period. It requires a timely initiation of an effective treatment because newborn infants are especially vulnerable to damage caused by bilirubin in the central nervous system due to the characteristics typical of this stage of life.High bilirubin levels result in neurotoxicity and oxidative stress. However, molecular biology studies have demonstrated that bilirubin itself acts as a potent antioxidant.The objective of this update is to review the processes whereby bilirubin causes cell damage and determine its beneficial antioxidant effects. Knowing these mechanisms may facilitate a more accurate indication of a customized, effective, and timely phototherapy. Until new scientific advances are made, phototherapy should be prescribed based on expert consensus.
Assuntos
Humanos , Masculino , Feminino , Recém-Nascido , Bilirrubina , Estresse Oxidativo , Síndromes Neurotóxicas , AntioxidantesRESUMO
Hyperbilirubinemia is the most common reason for consultation and hospitalization in the neonatal period. It requires a timely initiation of an effective treatment because newborn infants are especially vulnerable to damage caused by bilirubin in the central nervous system due to the characteristics typical of this stage of life. High bilirubin levels result in neurotoxicity and oxidative stress. However, molecular biology studies have demonstrated that bilirubin itself acts as a potent antioxidant. The objective of this update is to review the processes whereby bilirubin causes cell damage and determine its beneficial antioxidant effects. Knowing these mechanisms may facilitate a more accurate indication of a customized, effective, and timely phototherapy. Until new scientific advances are made, phototherapy should be prescribed based on expert consensus.
La hiperbilirrubinemia es el motivo más frecuente de consulta e internación en el período neonatal. Requiere la instauración oportuna de un tratamiento eficiente, ya que los recién nacidos son especialmente vulnerables a los daños que la bilirrubina puede causar en el sistema nervioso central, debido a características propias de esta etapa de la vida. La bilirrubina en altas concentraciones produce neurotoxicidad y estrés oxidativo. Sin embargo, estudios de biología molecular demuestran que la misma molécula se comporta como un potente antioxidante. El objetivo de esta actualización es revisar cuáles son los procesos por los que la bilirrubina genera daño celular y cuáles son sus efectos antioxidantes beneficiosos. Conocer estos mecanismos facilitaría una indicación más precisa de luminoterapia individualizada, eficaz y oportuna. Hasta nuevos avances científicos, la prescripción de este tratamiento debe ser orientada por consenso de expertos.
Assuntos
Antioxidantes , Bilirrubina , Bilirrubina/metabolismo , Humanos , Hiperbilirrubinemia , Estresse Oxidativo , FototerapiaRESUMO
Description Infantile botulism is a potentially devastating disease caused by ingestion of Clostridium botulinum spores through food products or dust particles. The toxin produced by the spores can lead to descending paralysis requiring hospitalization for supportive care which sometimes includes mechanical ventilation. Human Botulism Immune Globulin-Intravenous (BIG-IV or BabyBIG) from the Infant Botulism Treatment and Prevention Program (IBTPP) has been shown to greatly improve outcomes. A previously healthy 5-month-old infant was admitted to her regional hospital for poor feeding and lethargy. When the weakness progressed and she had trouble with protecting her airway, she was intubated and transferred to our institution. The primary diagnosis was infantile botulism and the decision was made to treat with BabyBIG. The pharmacy department was able to assist with obtaining BabyBIG, ensuring proper preparation, and coordinating the team for swift administration. In the days following the BabyBIG administration, the patient slowly started to recover her respiratory function and muscle tone. On day five of admission the patient was extubated. After transfer to the general pediatric floor the patient was given a transpyloric feeding tube and worked with gastrointestinal and nutrition services to improve oral feeding. She was discharged on day seventeen with plans to continue working with therapy and nutrition. BIG-IV can have a major impact in the recovery of infantile botulism. Pharmacists are in an optimal position to assist with coordinating the multidisciplinary team regarding its procurement, preparation, and administration.
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Caso clínico de un hombre de 20 años, procedente de área rural de un municipio de Nariño, que consulta a un centro de salud después de 36 horas de haber ingerido de modo no intencional 20-30 mL de gramoxone (dicloruro de paraquat) mientras estaba en estado de embriaguez, con síntomas digestivos, hiperbilirrubinemia, elevación de azoados, leucocitosis y neutrofilia, por lo que es referido a un hospital de alta complejidad en la ciudad de Pasto. Durante su hospitalización, presenta epistaxis, falla renal con requerimiento de hemodiálisis, quemaduras orales, hipertermia y dos episodios de crisis convulsivas tónico-clónico generalizadas. Se toman paraclínicos: azoados, gases arteriales, electrolitos, glicemia, entre otros, cuyos resultados se enmarcan dentro de la normalidad durante los episodios convulsivos. Es relevante proporcionar elementos para construir un criterio clínico que explique el compromiso neurológico, ya que, es raro y complejo en intoxicaciones por herbicidas como el paraquat.
A clinical case of a 20 year-old man from a rural area of Llorente-Nariño, who consulted a local health center after 36 hours of accidental ingesting Gramoxone (paraquat dichloride, 20-30 mL), while under the influence of alcohol, that provoked digestive symptoms, hyperbilirubinemia, elevation of creatinine and hemogram with leukocytosis and neutrophilia, is referred to the third level of health attention in the city of Pasto. During the hospital course he presents epistaxis, kidney failure with need of hemodialysis, oral burns, hyperthermia and two episodes of convulsive seizures clonic-tonic generalized with arterial blood gases, electrolytes, glycemia and other para-clinics within normal ranges during the seizures. It's important to try to give elements to build a clinical criteria to explain neurologic compromise, because is exceptionally strange and complex this type of clinical presentation in cases of intoxication with paraquat.Keywords: paraquat; herbicides; poisoning; neurotoxicity syndromes.
Caso clínico de um homem de 20 anos, procedente de área rural de um munícipio de Nariño, que consulta a um centro de saúde depois de 36 horas de haver ingerido de modo não intencional 20-30 mL de gramoxone (dicloreto de Paraquat) enquanto estava em estado de embriaguez, com sintomas digestivos, hiperbilirrubinemia, elevação de azoados, leucocitose e neutrofilia, pelo que é referido a um hospital de alta complexidade na cidade de Pasto. Durante sua hospitalização, apresenta epistaxe, falha renal com requerimento de hemodiálise, queimaduras orais, hipertermia e dois episódios de crise convulsivas tônico-clônico generalizadas. Se tomam paraclínicos: azoados, gases arteriais, eletrólitos, glicemia, entre outros, cujos os resultados se quadram dentro da normalidade durante os episódios convulsivos. É relevante proporcionar elementos para construir um critério clínico que explique o compromisso neurológico, já que, é raro e complexo em intoxicações por herbicidas como o paraquat.
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Humanos , Paraquat , Intoxicação , Síndromes Neurotóxicas , HerbicidasRESUMO
BACKGROUND: Colorectal carcinoma (CRC) is widely treated by chemotherapy based on an intensely neurotoxic drug: oxaliplatin (OXL). We objective to evaluate prospectively the orofacial neurotoxicity during FLOX (fluorouracil + leucovorin + OXL) chemotherapy. METHODS: So, 46 patients with CRC were prospectively evaluated during FLOX chemotherapy by 3 cycles (C) of 6 weeks (W) each. We weekly applied the orofacial section of the Acute and Chronic Neuropathy Questionnaire of Common Toxicity Criteria for Adverse Events of the National Cancer Institute of the United States of America (Oxaliplatin-specific neurotoxicity scale). Patients were asked the following concerning the severity (scores 0-5) of orofacial symptoms: jaw pain, eyelids drooping, throat discomfort, ear pain, tingling in mouth, difficulty with speech, burning or discomfort of the eyes, loss of any vision, feeling shock/pain down back and problems breathing. We summed the scores (0-50) and evaluated the clinicopathological data. Friedman/Dunn, Chi square and multinomial regression logistic tests were used (SPSS 20.0, p < 0.05). RESULTS: There was a significant increase in sum of orofacial neurotoxicity from baseline to C1.W3, C2.W1 and C3.W5 (p < 0.001) due increase in scores of jaw pain (p < 0.001), eyelids drooping (p = 0.034), throat discomfort (p < 0.001), ear pain (p = 0.034), tingling in mouth (p = 0.015), burning/discomfort of your eyes (p < 0.001), loss of any vision (p < 0.001), feeling shock/pain down back (p < 0.001), problems with breathing (p = 0.045), but not difficulty with speech (p = 0.087). Women (p = 0.021) and young patients (p = 0.027) had significant higher prevalence of orofacial neurotoxicity. CONCLUSIONS: FLOX-related orofacial neurotoxicity begins acutely and remains long term with increased incidence in women and younger patients.
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Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias Colorretais/tratamento farmacológico , Síndromes Neurotóxicas/etiologia , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/patologia , Face , Feminino , Fluoruracila/administração & dosagem , Humanos , Incidência , Leucovorina/administração & dosagem , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Boca/efeitos dos fármacos , Síndromes Neurotóxicas/epidemiologia , Oxaliplatina/administração & dosagem , Doenças do Sistema Nervoso Periférico/epidemiologia , Estudos ProspectivosRESUMO
Purpose Studies have demonstrated that star fruit consumption by nephropathic patients triggers severe neurotoxic effects that can lead to convulsions or even death. Brain areas likely susceptible to star fruit poisoning have not been investigated. The objective of the present study was to map possible epileptogenic areas susceptible to star fruit intoxication in nephropathic rats. Methods The study analyzed 25 rats (5 groups). Rats in the experimental group underwent bilateral ureteral obstruction surgery and orogastric gavages with star fruit juice. An electroencephalogram was used to confirm convulsive seizures. Urea and creatinine levels were used to confirm the uremia model. Immunohistochemical analysis was used to map cells with c-Fos protein (c-Fos+ cells) to identify brain areas with increased neuronal activity. Control groups included non-nephropathic and nephropathic rats that did not receive star fruit. Results A statistically significant increase (p 0.01) in c-Fos+ cells was noted in nephropathic animals receiving star fruit juice compared to control groups, in brain areas commonly related to epileptogenic neural circuits including the hippocampus, amygdala, rhinal cortex, anterior cingulate area, piriform area, and medial dorsal thalamus. Conclusion These data corroborate the neurotoxic capacity of star fruit in nephropathic patients.(AU)
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Animais , Masculino , Ratos , Averrhoa/toxicidade , Convulsões , Nefropatias , Síndromes Neurotóxicas , Modelos AnimaisRESUMO
Abstract Purpose Studies have demonstrated that star fruit consumption by nephropathic patients triggers severe neurotoxic effects that can lead to convulsions or even death. Brain areas likely susceptible to star fruit poisoning have not been investigated. The objective of the present study was to map possible epileptogenic areas susceptible to star fruit intoxication in nephropathic rats. Methods The study analyzed 25 rats (5 groups). Rats in the experimental group underwent bilateral ureteral obstruction surgery and orogastric gavages with star fruit juice. An electroencephalogram was used to confirm convulsive seizures. Urea and creatinine levels were used to confirm the uremia model. Immunohistochemical analysis was used to map cells with c-Fos protein (c-Fos+ cells) to identify brain areas with increased neuronal activity. Control groups included non-nephropathic and nephropathic rats that did not receive star fruit. Results A statistically significant increase (p<0.01) in c-Fos+ cells was noted in nephropathic animals receiving star fruit juice compared to control groups, in brain areas commonly related to epileptogenic neural circuits including the hippocampus, amygdala, rhinal cortex, anterior cingulate area, piriform area, and medial dorsal thalamus. Conclusion These data corroborate the neurotoxic capacity of star fruit in nephropathic patients.
Assuntos
Humanos , Animais , Ratos , Proteínas Proto-Oncogênicas c-fos , Frutas , Nefropatias , Encéfalo , Córtex Cerebral , Proteínas Proto-Oncogênicas c-fos/metabolismo , Proteínas Proto-Oncogênicas c-fos/metabolismo , Frutas/intoxicação , Frutas/intoxicação , Hipocampo , Nefropatias , Nefropatias/complicaçõesRESUMO
Resumen: Introducción: la marihuana es la sustancia de abuso más consumida en América y Europa después del alcohol. En Uruguay la prevalencia es cercana a 23%. El principio activo delta 9-tetrahidrocannabinol es responsable de los efectos psicoactivos. La principal fuente en un niño es una parte de la planta, cigarrillo o comestible con cannabis proveniente de un familiar o vecino. La intoxicación puede ser más severa en niños que en adultos. En Uruguay, en 2013, se aprobó la ley 19.172 que regula el mercado de cannabis, generando un nuevo escenario con potencial riesgo para la población pediátrica. Objetivo: comunicar casos clínicos de intoxicación aguda no intencional por cannabis asistidos entre marzo y junio de 2017, analizar circunstancias de exposición, manifestaciones clínicas, severidad y evolución. Observación clínica: cuatro niños (9 meses, 1, 2 y 8 años) fueron asistidos. En todos ellos la vía de ingreso fue oral en ambiente doméstico. Presentaron síntomas neurológicos agudos: depresión de conciencia, convulsiones, distonías, ataxia, irritabilidad. Requirieron medidas de sostén, descontaminación digestiva y exámenes de laboratorio ampliado. El screening en orina fue positivo en cuatro casos. En dos se realizó la técnica confirmatoria. Aplicando el Poisoning Severity Score, todos sufrieron intoxicación moderada. Se asistieron en conjunto con toxicólogo clínico. Conclusiones: los niños que presentan síntomas predominantemente neurológicos de instalación aguda sin una causa evidente, pueden presentar intoxicación aguda por cannabis, sobre todo cuando en el entorno doméstico hay consumo, cultivo o ambos. Debemos mantener una vigilancia activa. Seguramente futuras investigaciones contribuirán a definir la necesidad de establecer estrategias de prevención destinadas a la población infantil con el objetivo de disminuir el potencial efecto no deseado de este nuevo escenario.
Summary: Introduction: marijuana is most highly consumed abuse substance in America and Europe after alcohol. In Uruguay, the prevalence is close to 23%. The active ingredient, delta 9-tetrahydrocannabinol, is responsible for its psychoactive effects. The main source of access for a child involves a relative and/or neighbor. Intoxication may be more severe in children, In 2013,.cannabis-sale regulating Act 19.172 was approved in Uruguay, and it generated a new potentially risky scenario for children. Objective: report clinical cases of severe unintentional intoxication from cannabis between March and June 2017, and analyze circumstances that led to exposure, clinical manifestations, severity and evolution. Clinical observation: 4 children (9 months, 1, 2 and 8 years of age) were assisted. In all cases, they had ingested cannabis in their home environment. They presented severe neurological symptoms: depressed level of consciousness, convulsive seizures, dystonia, ataxia, irritability. They required supportive measures, digestive decontamination and additional laboratory tests. Urine screening was positive in 4 cases. In 2, we performed confirmatory technique. As per the Poisoning Severity Score, all children suffered moderate intoxication. They were assisted jointly by a clinical toxicologist. Conclusions: children showing predominantly acute neurological symptoms with no apparent cause can be the subject of severe cannabis intoxication, especially when cannabis consumption takes place in their household environments. Surveillance is needed and future research will certainly contribute to the creation of prevention strategies with the purpose of reducing the potential unwanted consequences of this new scenario for children.
Resumo: Introdução: a maconha é a substância do abuso mais consumida na América e na Europa depois do álcool. No Uruguai, a prevalência é próxima de 23%. O ingrediente ativo delta 9-tetrahydrocannabinol é responsável pelos efeitos psicoativos. A principal fonte de acesso à marijuana por parte duma criança é ingerir uma parte da planta, cigarro ou comestível com cânabis de um parente e / ou vizinho. A intoxicação pode ser mais grave em crianças do que em adultos. No Uruguai, em 2013, a Lei 19.172 foi aprovada e regulou a venda de cânabis, gerando um novo cenário com risco potencial para as crianças. Objetivo: relatar casos clínicos de intoxicação aguda não intencional por cânabis atendidos entre março e junho de 2017, analisar as circunstâncias de exposição, manifestações clínicas, gravidade e evolução. Observação clínica: 4 crianças (9 meses, 1, 2 e 8 anos de idade) foram atendidas. Todos eles ingeriram cânabis num ambiente doméstico. Apresentaram sintomas neurológicos agudos: depressão da consciência, convulsões, distonia, ataxia, irritabilidade. Eles precisaram de medidas de suporte, descontaminação digestiva e testes de laboratório adicionais. O screening de urina foi positivo em 4 casos. Em 2, a técnica confirmatória foi realizada. Utilizando o Poisoning Severity Score, todos sofreram intoxicação moderada. Eles foram assistidos conjuntamente pelo toxicologista clínico. Conclusões: é possível que crianças que apresentam sintomas neurológicos predominantemente de instalação aguda sem causa evidente, apresentem intoxicação aguda por cânabis, especialmente quando existe consumo no ambiente ou na cultura domésticos. Nós devemos manter uma vigilância ativa. Com certeza, futuras pesquisas contribuirão para definir estratégias de prevenção para crianças, com o objetivo de reduzir o potencial efeito indesejado desse novo cenário.
RESUMO
La colistina o polimixina E es un antibiótico cuyo uso fue descontinuado por la toxicidad renal y neurológica relacionadas al uso de colistina sulfato. Estos efectos adversos han disminuido con el uso del profármaco colistimetato sódico. Actualmente el uso de colistina es más frecuente debido al incremento de infecciones ocasionadas por bacilos Gram negativos multirresistentes, sobre todo en las unidades de cuidados intensivos. Presentamos el caso de una mujer de 50 años de edad con antecedente de consumo de anti-inflamatorios no esteroideos y corticoides, pos- operada de perforación gástrica que evolucionó con colecciones abdominales por Acinetobacter sp. multirresistente. Recibió 34 días de colistina endovenosa y desarrolló hiperpigmentación cutánea, ataxia (neurotoxicidad) y falla renal (nefrotoxicidad) de forma secuencial secundaria a la administración de colistina, los efectos adversos desaparecieron con la suspensión del antibiótico. (AU)
Colistin or polymycin E is an antibiotic that was discontinued due to its renal and neurologic toxicity related to its colistin sulfate content. These adverse effects have been reduced with the use of sodium colistemathe. There is currently a more frequent use of colistin due to an increase of multi-resistant Gram negative infections, particularly in intensive care units. We present the case of a 50-year-old woman with history of surgery due to gastric perforation, use of steroids and non-steroidal anti-inflammatory drugs, that developed intra-abdominal abscesses due to multidrug resistant Acinetobacter spp. She received 34 days of intravenous colistin and developed skin hyperpigmentation, ataxia and renal failure. These adverse effects disappeared with discontinuation of the drug. (AU)
Assuntos
Humanos , Feminino , Pessoa de Meia-Idade , Hiperpigmentação , Colistina/toxicidade , Colistina/uso terapêutico , Síndromes NeurotóxicasRESUMO
Resumo Objetivo Investigar a prevalência e incidência de neuropatia periférica relacionada ao tratamento com antineoplásicos de pessoas com mieloma múltiplo bem como a associação entre os esquemas quimioterápicos e a neuropatia periférica após o tratamento. Método Estudo documental, correlacional, realizado em dois locais de referência para tratamento oncológico, localizados nos estados do Ceará e Minas Gerais, com análise de pacientes atendidos entre janeiro/2013 e janeiro/2016. Os dados foram analisados utilizando-se análise descritiva e inferencial a partir dos testes qui-quadrado e exato de fisher. Resultados Foram avaliados 100 prontuários de pessoas com mieloma múltiplo com média de idade de 62,7 anos, maioria de homens (64%). O esquema quimioterápico mais utilizado (60%) foi o bortezomibe, dexametasona e ciclofosfamida; 20% dos pacientes apresentavam neuropatia periférica antes do tratamento, 68% desenvolveram durante o tratamento e 56% ao finalizar o tratamento. Não houve associação entre os esquemas quimioterápicos e a neuropatia periférica após o tratamento. Conclusão O presente estudo mostrou um aumento da incidência de NP em indivíduos em tratamento para o MM, 80% apresentaram sintomas de neuropatia antes e/ou durante e/ou após o tratamento com esquemas quimioterápicos. A predominância foi de homens idosos aposentados. O esquema quimioterápico mais utilizado foi o VDC e não foi identificada associação entre os esquemas utilizados e a NP após término o tratamento. As implicações dessas observações recaem sobre a necessidade de avaliação contínua da NP em pessoas com MM, além da monitorização rigorosa desse evento no decorrer do tratamento e após o mesmo, bem como o manejo dos eventos adversos e alterações relacionadas a doença. Não houve associação entre os esquemas quimioterápicos e a neuropatia periférica após o tratamento. Espera-se que os resultados obtidos auxiliem na organização de um registro de dados sobre NP em pacientes com câncer, com o objetivo principal de determinar alvos de intervenção, tornando o cuidado mais eficiente e integral.
Resumen Objetivo investigar la prevalencia e incidencia de la neuropatía periférica relacionada al tratamiento con antineoplásicos de personas con mieloma múltiple, así como la asociación entre los regímenes de quimioterapia y neuropatía periférica después de tratamiento. Método Estudio documental, correlativo, realizado en dos puntos de referencia para el tratamiento del cáncer, los cuales se encuentran en los estados de Ceará y Minas Gerais, con análisis de pacientes tratados entre enero / 2013 y enero / 2016. Los datos fueron analizados utilizando el análisis descriptivo e inferencial a partir de las pruebas qui-cuadrado y exacto de Fisher. Resultados Fueron evaluados 100 expedientes de personas con mieloma múltiple con una edad media de 62,7 años, siendo la mayoría hombres (64%). El esquema quimioterápico más utilizado (60%) fue el bortezomib, dexametasona y ciclofosfamida; el 20% de los pacientes presentaban neuropatía periférica antes del tratamiento, el 68% la desarrolló durante el tratamiento y el 56% al finalizar el tratamiento. No hubo asociación entre los esquemas quimioterápicos y la neuropatía periférica después del tratamiento. Conclusión Este estudio mostró una mayor incidencia de NP en individuos que reciben tratamiento para MM, el 80% presentó síntomas de neuropatía antes y / o durante y / o después del tratamiento con regímenes de quimioterapia. La predominancia fue de hombres ancianos jubilados. El esquema quimioterápico más utilizado fue el VDC y no se identificó asociación entre los esquemas utilizados y la NP después de terminar el tratamiento. Las implicaciones de estas observaciones recaen sobre la necesidad de evaluación continua de la NP en personas con MM, además del monitoreo riguroso de dicho evento durante el tratamiento y después del mismo, así como el manejo de los eventos adversos y alteraciones relacionadas con la enfermedad. No hubo asociación entre los esquemas quimioterápicos y la neuropatía periférica después del tratamiento. Se espera que los resultados obtenidos ayuden en la organización de un registro de datos sobre NP en pacientes con cáncer, con el objetivo principal de determinar metas de intervención, obteniendo una atención más eficiente e integral.
Abstract Objective To investigate the prevalence and incidence of peripheral neuropathy (PN) related to antineoplastic therapy in people with multiple myeloma and the association between chemotherapy regimens and peripheral neuropathy after treatment. Method This is a documentary and correlational study carried out in two reference sites for cancer treatment, located in the Brazilian states of Ceará and Minas Gerais, with an analysis of patients treated between January 2013 and January 2016. A descriptive and inferential analysis of data was carried out by means of chi-square and Fischer's exact tests. Results The study assessed 100 medical records of people with multiple myeloma, who were aged 62.7 years on average and were mostly men (64%). The most used chemotherapy regimen (60%) was bortezomib, dexamethasone, and cyclophosphamide; 20% of patients had peripheral neuropathy before treatment, 68% had it during treatment and 56% at the end of treatment. There was no association between chemotherapy regimens and peripheral neuropathy after treatment. Conclusion Our study showed an increase in the incidence of PN in individuals undergoing treatment of multiple myeloma, 80% had symptoms of neuropathy before and/or during and/or after treatment with chemotherapy regimens. Predominance was of elderly retired men. The most common chemotherapy regimen was bortezomib/dexamethasone/cyclophosphamide and there was no association between regimens used and PN after treatment. The implications of these observations rest on the need for a permanent assessment of PN in people with multiple myeloma, in addition to a strict follow-up to this event in the course of treatment and after it, as well as the management of adverse events and alterations related to the disease. There was no association between chemotherapy regimens and peripheral neuropathy after treatment. It is expected that the results obtained help in the organization of a data record about PN in patients with cancer, with the main purpose of establishing targets of intervention, thus making care more efficient and comprehensive.
Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Dexametasona/uso terapêutico , Prontuários Médicos , Síndromes Neurotóxicas , Ciclofosfamida/uso terapêutico , Bortezomib/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Manifestações Neurológicas , Epidemiologia Descritiva , Antineoplásicos Hormonais/uso terapêutico , Antineoplásicos Alquilantes/uso terapêutico , Quimioterapia Combinada , Estudos de Avaliação como Assunto , Correlação de Dados , Octogenários , Inferência Estatística , Antineoplásicos/uso terapêuticoRESUMO
Posterior reversible encephalopathy syndrome is an illness with multiple causes and distinctive clinicalradiological characteristics that should be known by intensivists and emergency room physicians for a timely diagnosis and treatment. A fatal case of posterior reversible encephalopathy syndrome is presented, and the risk factors related to the outcome are identified.A 60-year-old man without a relevant medical history arrived at the emergency room presenting with depressed consciousness, seizures, and high blood pressure. Tomographic images revealed a posterior cerebellar hematoma. Resonance images showed ischemic zones, vasogenic edema from the thalamus to the brain stem, middle cerebellar peduncles, deep white matter of the cerebral hemispheres, and zones of hemorrhagic transformation. Despite medical-surgical management, the patient died. The risk factors described as the cause of the fatal outcome were identified. This case demonstrates that posterior reversible encephalopathy syndrome can occur without triggering risk factors and highlights the need for early recognition to establish an appropriate intervention to avoid injury or a fatal outcome. Cases of posterior reversible encephalopathy syndrome provide opportunities to investigate the susceptibility for the development of this condition and to establish appropriate preventive measures.
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Tronco Encefálico/fisiologia , Encéfalo/fisiologia , Síndrome da Leucoencefalopatia Posterior , Convulsões/complicações , Humanos , Imageamento por Ressonância Magnética , Masculino , Prognóstico , Convulsões/fisiopatologiaRESUMO
El síndrome de encefalopatía posterior reversible es una condición que responde a múltiples causas y presenta características clínicas o radiológicas distintivas; los intensivistas y los médicos de urgencias deben conocerlo con el fin de hacer el diagnóstico y ordenar el tratamiento oportuno. Se presenta un caso fatal de síndrome de encefalopatía posterior reversible, en el cual se determinaron los factores de riesgo relacionados con el resultado final. Un hombre de 60 años sin antecedentes médicos ingresó por urgencias con depresión de la conciencia, convulsiones y tensión arterial elevada. Las imágenes de la tomografía revelaron un hematoma cerebeloso posterior, y las de resonancia magnética mostraron zonas isquémicas, edema vasogénico que se extendía desde los tálamos hacia el tallo cerebral, los pedúnculos cerebelosos medios y la sustancia blanca profunda de los hemisferios cerebelosos, así como zonas de transformación hemorrágica. A pesar del tratamiento médico y quirúrgico recibido, el paciente falleció. Se determinaron los factores de riesgo que se han descrito como causa de muerte en este síndrome. Este caso demuestra que dicho síndrome puede ocurrir sin que se hayan detectado factores de riesgo desencadenantes y pone en evidencia la necesidad de su reconocimiento temprano para establecer una intervención adecuada y evitar daños o un desenlace fatal. Además, abre el camino a nuevos estudios sobre la propensión a desarrollarlo y las medidas preventivas que pueden adoptarse.
Posterior reversible encephalopathy syndrome is an illness with multiple causes and distinctive clinicalradiological characteristics that should be known by intensivists and emergency room physicians for a timely diagnosis and treatment. A fatal case of posterior reversible encephalopathy syndrome is presented, and the risk factors related to the outcome are identified. A 60-year-old man without a relevant medical history arrived at the emergency room presenting with depressed consciousness, seizures, and high blood pressure. Tomographic images revealed a posterior cerebellar hematoma. Resonance images showed ischemic zones, vasogenic edema from the thalamus to the brain stem, middle cerebellar peduncles, deep white matter of the cerebral hemispheres, and zones of hemorrhagic transformation. Despite medical-surgical management, the patient died. The risk factors described as the cause of the fatal outcome were identified. This case demonstrates that posterior reversible encephalopathy syndrome can occur without triggering risk factors and highlights the need for early recognition to establish an appropriate intervention to avoid injury or a fatal outcome. Cases of posterior reversible encephalopathy syndrome provide opportunities to investigate the susceptibility for the development of this condition and to establish appropriate preventive measures.
Assuntos
Síndrome da Leucoencefalopatia Posterior , Edema Encefálico , Imageamento por Ressonância Magnética , Hemorragia Cerebral , Síndromes Neurotóxicas , Substância BrancaRESUMO
ABSTRACT Objectives: to estimate the prevalence of impaired tactile sensory perception, identify risk factors, and establish a risk prediction model among adult patients receiving antineoplastic chemotherapy. Method: historical cohort study based on information obtained from the medical files of 127 patients cared for in the cancer unit of a private hospital in a city in Minas Gerais, Brazil. Data were analyzed using descriptive and bivariate statistics, with survival and multivariate analysis by Cox regression. Results: 57% of the 127 patients included in the study developed impaired tactile sensory perception. The independent variables that caused significant impact, together with time elapsed from the beginning of treatment up to the onset of the condition, were: bone, hepatic and regional lymph node metastases; alcoholism; palliative chemotherapy; and discomfort in lower limbs. Conclusion: impaired tactile sensory perception was common among adult patients during chemotherapy, indicating the need to implement interventions designed for early identification and treatment of this condition.
RESUMO Objetivos: Estimar a prevalência de percepção sensorial tátil alterada, identificar os fatores de risco e estabelecer modelo de predição de risco para seu desenvolvimento, em pacientes adultos, submetidos à quimioterapia antineoplásica. Método: Coorte histórica realizada a partir de informações obtidas em prontuários de 127 pacientes atendidos em uma unidade oncológica de um hospital privado de um município de Minas Gerais, Brasil. Os dados foram analisados por estatística descritiva, bivariada, com análise de sobrevida e multivariada por regressão de Cox. Resultados: Dos 127 pacientes analisados 57% desenvolveu percepção sensorial tátil alterada. As variáveis independentes que impactaram, de forma significativa e conjunta, com o tempo para ocorrência do desfecho foram: metástases óssea, hepática e de linfonodo regional, alcoolismo, quimioterapia paliativa e desconforto nos membros inferiores. Conclusão: A percepção sensorial tátil alterada foi um achado comum em pacientes adultos durante o tratamento quimioterápico, apontando para a necessidade da implementação de intervenções que visem identificar precocemente e prevenir ou tratar o problema.
RESUMEN Objetivos: estimar la prevalencia de percepción sensorial táctil alterada, identificar los factores de riesgo y establecer un modelo de predicción de riesgo para su desarrollo, en pacientes adultos sometidos a quimioterapia antineoplásica. Método: estudio de cohorte histórica, realizado a partir de informaciones obtenidas de fichas médicas de 127 pacientes atendidos en unidad oncológica de un hospital privado, en municipio de Minas Gerais, Brasil. Los datos fueron analizados con estadística descriptiva, bivariada, con análisis de sobrevivencia y multivariado con la regresión de Cox. Resultados: de los 127 pacientes analizados, 57% desarrollaron percepción sensorial táctil alterada. Las variables independientes que causaron impacto de forma significativa, y conjuntamente con el tiempo para ocurrencia del resultado, fueron: metástasis ósea, hepática y de linfoma regional; alcoholismo; quimioterapia paliativa; e, incomodidad en los miembros inferiores. Conclusión: la percepción sensorial táctil alterada fue un hallazgo común en pacientes adultos durante el tratamiento quimioterápico, lo que apunta para la necesidad de la implementación de intervenciones que objetiven identificar precozmente y prevenir o tratar el problema.