Actualización en el manejo de intoxicación sistémica por anestésicos locales / Local anesthetics systemic toxicity: update in management

Systemic toxicity by local anesthetics an adverse reaction that occurs when local anesthetics (AL) reach significant systemic levels, primarily affects the central and cardiovascular nervous system, and while it is an infrequent event, it can be potentially fatal. The main determinant of the toxicity is the plasma concentration of LA, especially the free fraction. The most serious symptoms are seizures and cardiac arrest, which can occur with the administration of any LA. Bupivacaine is the most cardiotoxic of the commonly used LAs, followed in decreasing order by levobupivacaine, ropivacaine and lidocaine.

La intoxicación sistémica por anestésicos locales (ISAL), una reacción adversa que ocurre cuando los anestésicos locales (AL) alcanzan niveles sistémicos significativos, afecta principalmente al sistema nervioso central y cardiovascular, y si bien, es un evento infrecuente, puede ser potencialmente fatal. El principal determinante de la ISAL es la concentración plasmática de AL, en especial la fracción libre. Los síntomas más graves son las convulsiones y paro cardíaco, los cuales pueden ocurrir con la administración de cualquier AL. La bupivacaína es el más cardiotóxico de los AL comúnmente utilizados, seguido en orden decreciente por levobupivacaína, ropivacaína y lidocaína.

Tóxicos ambientales y su efecto sobre el neurodesarrollo / [Environmental toxic and its effect on neurodevelopment].

Neurodevelopmental disorders are the result of a disturbance of brain function. They are frequent, with varied symptomatology, manifest themselves at different times of life and tend to be persistent with impact at the individual, family and social level. The association of these disorders with genetic entities is low. Although the research supports a mode of genetic inheritance, epigenetic factors and environmental factors can play an important role. In recent years there was a striking increase of these disorders especially attention deficit hyperactivity disorders and pervasive development disorder. Environmental factors such as the intoxication of the fetus by especially heavy metals lead and mercury are to blame in some children, of these disorders. Other substances of wide use, little degradation and maintenance in the food chain as pesticides, polychlorinated biphenyls and now the recycling of electronic waste put especially infants and children at risk, and even more so in the developing countries.

Impacto en la salud y el medio ambiente por exposición a plaguicidas e implementación de buenas prácticas agrícolas en el cultivo de tomate, Colombia, 2011 / Impact on health and environment of exposure to pesticides and implementation of best agricultural practices in tomato production, Colombia, 2011

Objetivo: describir los posibles efectos adversos en salud y medio ambiente por el uso de plaguicidas en zonas productoras de Colombia e implementar las buenas prácticas agrícolas (BPA) en el cultivo de tomate. Material y método: se realizó un estudio descriptivo en el municipio de La Merced-Caldas con tres fases: una de diagnóstico, donde se seleccionaron 132 trabajadores del sector agrícola y se recolectaron muestras biológicas y ambientales. Una segunda fase de intervención en la cual se incluyeron 5 parcelas, en estas se implementaron las (BPA) y una fase de evaluación de estas parcelas. Se llevó a cabo análisis simple de las variables y se exploraron posibles asociaciones. Resultados: el tiempo de exposición a plaguicidas en promedio fue de nueve años. Con mayor frecuencia el sistema nervioso central (95,5 por ciento) fue el más afectado; seguido por órganos de los sentidos (46,2 por ciento); sistema digestivo (33,3 por ciento ); piel (21,2 por ciento) y otros (19,7 por ciento). Se encontraron niveles de organoclorados en el 97,0 por ciento (128), inhibición de la enzima acetilcolinesterasa en el 34,1 por ciento (45) de los participantes y ningún nivel del metabolito etilentiourea. En las muestras ambientales se hallaron niveles de organofosforados en tomate y suelo. En el agua y lodo se detectaron niveles de organoclorados. La producción de tomate, mostró una diferencia estadísticamente significativa entre las parcelas con BPA y las tradicionales (p=0,020). Conclusiones: se evidenciaron los riesgos por uso de plaguicidas y la necesidad de fortalecer la vigilancia sobre los potenciales efectos para la salud que pueden producir los plaguicidas y mediante el empleo de las BPA.

Objective: Describe the possible adverse effects on population health and environment due to pesticide use in agricultural zones in Colombia, and implement the best agricultural practices (BAP) in tomato production. Materials and methods: A descript intoxicative study was carried out in the municipality of Merced-Caldas, consisting in three phases: a diagnostic phase, in which environmental and biological samples were collected, using a sample of 132 agricultural workers. In a second phase, BAP were implemented, and in the third phase, the results were evaluated. A univariate analysis was completed and posible associations were explored. Results: Average length of exposure to pesticides was 9 years. The central nervous system was the most affected (95.5 percent), followed by sensory organs (46.2 percent ), the digestive system (33.3 percent ), skin (21.2 percent) and others (19.7 percent). Organoclorides were found in 97.0 percent (128), inhibition of acetylcholinesterase enzyme was found in 43.1 percent (45); no metabolite ethylenethiourea was found. In the environmental samples, presence of organophosphates was found in tomatoes and soil. In water and mud samples, organochlorides were found. There was a statistically significant difference between BPA farms and traditional farms. (p=0,020). Conclusions: Risks due to pesticide use were demonstrated, and the need to strengthen vigilance on the potential effects of pesticide use.

Exposición a solventes y disfunción auditiva central: revisión de la evidencia científica / Solvent exposure and central auditory dysfunction: a literature review on the scientific evidence

Diversos estudios han demostrado que los solventes orgánicos pueden inducir una disfunción auditiva. Los modelos animales han mostrado que los solventes son capaces de dañar las células ciliadas externas. Estudios de campo en trabajadores expuestos a solventes han encontrado por una parte, una mayor prevalencia de hipoacusia sensorioneural en comparación a grupos controles, y por otra, una dis función auditiva central asociada a la exposición a solventes. El presente trabajo tiene como objetivo revisar y discutir la evidencia científica acerca de la disfunción auditiva central asociada a la exposición a solventes como el tolueno, estireno, xileno, bisulfato de carbono, y mezcla de ellos. Se discuten los resultados de las investigaciones llevadas a cabo en humanos expuestos laboralmente a estos agentes. Se discuten además, los mecanismos de ototoxicidady neurotoxidad de los solventes y sus implicancias en la evaluación de la hipoacusia inducida por solventes.

Different studies have demonstrated that solvents may induce an auditory dysfunction. Animal models have shown that solvents can injure the outer hair cells. Studies conducted in workers exposed to solvents have found on one hand, a higher prevalence of sensorineural hearing loss in comparison to non-exposed control group subjects. On the other hand, these studies have found a central auditory dysfunction associated with solvent exposure. The present manuscript aims at revising and discussing the scientific evidence on central auditory dysfunction associated with exposure to solvents such as toluene, styrene, xylene, carbon disulphate, and mixtures. Results from studies conducted in humans occupationally exposed to solvents are discussed. Also, the oto-and neuro-toxicity induced by solvents and the implications for the assessment of solvent-induced hearing loss are addressed.

Occupational Neurological Disorders in Korea

The purpose of this article was to provide a literature review of occupational neurological disorders and related research in Korea, focusing on chemical hazards. We reviewed occupational neurological disorders investigated by the Occupational Safety and Health Research Institute of Korean Occupational Safety and Health Agency between 1992 and 2009, categorizing them as neurological disorders of the central nervous system (CNS), of the peripheral nervous system (PNS) or as neurodegenerative disorders. We also examined peer-reviewed journal articles related to neurotoxicology, published from 1984 to 2009. Outbreaks of occupational neurological disorder of the CNS due to inorganic mercury and carbon disulfide poisoning had helped prompt the development of the occupational safety and health system of Korea. Other major neurological disorders of the CNS included methyl bromide intoxication and chronic toxic encephalopathy. Most of the PNS disorders were n-hexane-induced peripheral neuritis, reported from the electronics industry. Reports of manganese-induced Parkinsonism resulted in the introduction of neuroimaging techniques to occupational medicine. Since the late 1990s, the direction of research has been moving toward degenerative disorder and early effect of neurotoxicity. To understand the early effects of neurotoxic chemicals in the preclinical stage, more follow-up studies of a longer duration are necessary.

In vitro and in vivo gene therapy with CMV vector-mediated presumed dog beta-nerve growth factor in pyridoxine-induced neuropathy dogs

Due to the therapeutic potential of gene therapy for neuronal injury, many studies of neurotrophic factors, vectors, and animal models have been performed. The presumed dog beta-nerve growth factor (pdbeta-NGF) was generated and cloned and its expression was confirmed in CHO cells. The recombinant pdbeta-NGF protein reacted with a human beta-NGF antibody and showed bioactivity in PC12 cells. The pdbeta-NGF was shown to have similar bioactivity to the dog beta-NGF. The recombinant pdbeta-NGF plasmid was administrated into the intrathecal space in the gene therapy group. Twenty-four hours after the vector inoculation, the gene therapy group and the positive control group were intoxicated with excess pyridoxine for seven days. Each morning throughout the test period, the dogs' body weight was taken and postural reaction assessments were made. Electrophysiological recordings were performed twice, once before the experiment and once after the test period. After the experimental period, histological analysis was performed. Dogs in the gene therapy group had no weight change and were normal in postural reaction assessments. Electrophysiological recordings were also normal for the gene therapy group. Histological analysis showed that neither the axons nor the myelin of the dorsal funiculus of L(4) were severely damaged in the gene therapy group. In addition, the dorsal root ganglia of L(4) and the peripheral nerves (sciatic nerve) did not experience severe degenerative changes in the gene therapy group. This study is the first to show the protective effect of NGF gene therapy in a dog model.

New antihistamines: a critical view

OBJETIVO: Avaliar criticamente os mais novos anti-histamínicos anti-H1 e os diferentes termos utilizados para denominá-los, com base na revisão de evidências sobre o papel dos anti-H1 no tratamento das doenças alérgicas. FONTES DOS DADOS: Artigos originais, revisões e consensos indexados nos bancos de dados MEDLINE e PUBMED de 1998 a 2006. Palavra chave: anti-histamínicos. SíNTESE DOS DADOS: Os anti-histamínicos de segunda geração diferenciam-se dos de primeira geração por sua elevada especificidade e afinidade pelos receptores H1 periféricos e pela menor penetração no sistema nervoso central (SNC), com conseqüente redução dos efeitos sedativos. Embora os anti-histamínicos de segunda geração sejam, geralmente, melhor tolerados do que seus predecessores, alguns efeitos adversos, principalmente cardiotoxicidade, surgiram com alguns deles. Nos últimos 20 anos, novos compostos, com diferentes farmacocinéticas, foram sintetizados. A maioria deles manifesta propriedades antiinflamatórias que independem de sua atividade no receptor H1. Aprimoramentos mais recentes, geralmente na forma de metabólitos ativos, levaram ao uso do termo anti-histamínico de terceira geração. Esse termo surgiu espontaneamente, sem uma descrição clara de seu significado e implicações clínicas, criando grande confusão entre os profissionais da saúde. CONCLUSÕES: Com base nas evidências sobre anti-histamínicos anti-H1, nenhum deles pode ser considerado como "anti-histamínico de terceira geração". Para tanto, seria preciso comprovar que a nova classe de anti-histamínicos possui vantagens clínicas distintas sobre os compostos existentes e preenche pelo menos três pré-requisitos: ausência de cardiotoxicidade, de interações medicamentosas e de efeitos sobre o SNC.

OBJECTIVE: To perform a critical evaluation of the more recent H1 antihistamines and the various terms used to describe them, based on a review of evidence on their role in the treatment of allergic disorders. SOURCES: Original articles, reviews and consensus documents published from 1998 to 2006 and indexed in the MEDLINE and PubMed databases. Keyword: antihistamines. SUMMARY OF THE FINDINGS: Second-generation antihistamines differ from first-generation ones because of their elevated specificity and affinity for peripheral H1 receptors and because of their lower penetration of the central nervous system (CNS), having fewer sedative effects as a result. Whilst second-generation antihistamines are in general better tolerated than their predecessors, some adverse effects, principally cardiotoxicity, have been observed with some of them. Over the last 20 years, new compounds with different pharmacokinetic properties have been synthesized. The majority of these exhibit anti-inflammatory properties that are independent of their action on the H1 receptor. More recent improvements, generally in the form of active metabolites, led to the use of the term third-generation antihistamines. This term emerged spontaneously, with no clear definition of its meaning or clinical implications, creating great confusion among healthcare professionals. CONCLUSIONS: On the basis of the evidence on H1 antihistamines, none of them deserve the title"third-generation antihistamine." As the Consensus Group on New Generation Antihistamines concluded, to merit this definition, a new class of antihistamines would have to demonstrate distinct clinical advantages over existing compounds and fulfill at least three prerequisites: they should be free from cardiotoxicity, drug interactions and effects on the CNS.

Prevención de los efectos adversos anticolinérgicos inducidos por los antipsicóticos en la 3ª edad: descripción de un caso en tratamiento con clozapina / Prevention of anticholinergic adverse effect induced by antipsychotics in aged: report of a case in treatment with clozapine

La seguridad y eficacia del uso de Clozapina en ancianos es actualmente objeto de estudio. Los pacientes geriátricos parecen presentar una mayor predisposición a sufrir hipotensión ortoestática y una mayor reactividad a los efectos anticolinérgicos, como también son más sensibles a los efectos adversos sobre el SNC. Se describe en el presente estudio el caso de una paciente portadora de un cuadro esquizofrénico catatónico en tratamiento con Clozapina, que presentó marcados síntomas anticolinérgicos y que mejoró de sus síntomas tras la suspensión del fármaco y el cambio a otro antipsicótico atípico (Risperidona). El estudio de niveles plasmáticos de Clozapina mostró que aún con 50 mg/día alcanzaba niveles plasmáticos de 200 ng/dl. Se analiza en el presente reporte la necesidad de una adecuada evaluación clínica y la importancia del control de Niveles Plasmáticos.

Effectiveness, safety and tolerability of gatifloxacin, a new 8-methoxyfluoroquinolone, in the treatment of outpatients with community-acquired pneumonia: a Brazilian study

OBJECTIVES: Evaluation of the effectiveness, safety and tolerability of gatifloxacin in the treatment of outpatients with community-acquired pneumonia (CAP). STUDY DESIGN: A prospective, multicenter, non-comparative clinical study carried out in Brazil. Voluntary, unpaid physician participation contributed to an unbiased study design. PATIENTS: Adult outpatients with clinical diagnosis of CAP. REGIMEN: Gatifloxacin, 400 mg PO once daily for 7 to 14 days. STUDY PROCEDURES: Initial clinical assessment, at the first day of gatifloxacin therapy; final evaluation after 7 to 14 days of treatment. RESULTS: According to the physicians assessments 97.3 of patients were cured or improved after gatifloxacin treatment. The incidence of adverse events was low and the most commonly reported events were nausea and dyspepsia. CONCLUSIONS: Gatifloxacin, 400 mg PO once daily for 7 to 14 days, is effective and safe in the treatment of patients with CAP.

Treatment of adults with community-acquired respiratory tract infections: results of a multicentric clinical trial with gatifloxacin

Respiratory tract infections have an important clinical and economic impact and they are the most common indication for antibiotic use in outpatient practice. This prospective, multicenter non-controlled trial assessed the efficacy and safety of gatifloxacin in the treatment of community-acquired respiratory tract infections. Patients were treated with a daily oral dose of gatifloxacin 400 mg for 7-14 days. The diagnosis of respiratory infection was made based on the clinical condition and/or radiologic findings. A total of 5,044 adult patients with community-acquired respiratory infections was treated with gatifloxacin in different centers in Brazil between March 1, 2001, and October 31, 2001. Among the 5,044 patients treated, 1,501 patients (29.76) had community-acquired pneumonia, 756 (14.99) had acute exacerbation of chronic bronchitis and 2,787 (55.25) had acute sinusitis. Of the total of patients treated, 3,607 (71.51) were considered cured, 1,261 (25) progressed with some clinical improvement, 28 (0.56) presented a relapse, 56 (1.11) failed to treatment and 92 (1.82) were unable to be evaluated. Adverse events were described in 634 (12.57) patients. The most common adverse events were: nausea (2.24); dyspepsia (1.86); diarrhea (0.79); change in taste (0.46); insomnia and irritability (0.22); dizziness (0.77); headache (0.42); allergic reaction (0.18); Central Nervous System alterations insomnia, agitation, anxiety (0.46). This study showed that the treatment of respiratory tract infections with gatifloxacin was safe and efficient and had a low incidence of adverse events.

Behaviour of oligodendrocytes and Schwann cells in an experimental model of toxic demyelination of the central nervous system

Oligodendrocytes and Schwann cells are engaged in myelin production, maintenance and repairing respectively in the central nervous system (CNS) and the peripheral nervous system (PNS). Whereas oligodendrocytes act only within the CNS, Schwann cells are able to invade the CNS in order to make new myelin sheaths around demyelinated axons. Both cells have some limitations in their activities, i.e. oligodendrocytes are post-mitotic cells and Schwann cells only get into the CNS in the absence of astrocytes. Ethidium bromide (EB) is a gliotoxic chemical that when injected locally within the CNS, induce demyelination. In the EB model of demyelination, glial cells are destroyed early after intoxication and Schwann cells are free to approach the naked central axons. In normal Wistar rats, regeneration of lost myelin sheaths can be achieved as early as thirteen days after intoxication; in Wistar rats immunosuppressed with cyclophosphamide the process is delayed and in rats administered cyclosporine it may be accelerated. Aiming the enlightening of those complex processes, all events concerning the myelinating cells in an experimental model are herein presented and discussed

Relato de desordens vestilococleares causadas por álcool / Report of vestibulo-cochlear disorders induced by alcohol

Este trabalho tem como objetivo demonstrar a necessidade e a importância da avaliaçäo otoneurológica neste tipo de paciente, muitas vezes visto exclusivamente pelo clínico geral e ignorado quanto aos seus distúrbios vestibulococleares

Clinical Study on Carbon Monoxide Intoxication in Children

Carbon monoxide intoxication has long been one of the most serious public health problems in Korea. This is mainly due to the wide use of anthracite coal briquettes as domestic fuel for cooking and under-the floor heating. One hundred and seven cases of CO intoxicated children hospitalized at Yonsei Medical center from January 1970 to December 1986 have been investigated clinically. The sex ratio was 1.3:1 (male 60 cases, female 47 cases) with the peak incidence occuring in patients between 12 and 14 years of age (28%). The most common symptoms were vomiting convulsions and headache; and the most frequent signs were altered mental state, increased deep tendon reflex and a positive Babinski sign. The outcome of patients was as follows: 4 cases (3.7%) expired, 77 cases (72.0%) recovered without neurologic sequelae and 26 cases (24.3%) survived with neurologic sequelae. The neurologic sequelae included persistent convulsions (7 cases), cortical blindness (3 cases), peripheral neuropathy (2 cases) and delayed neurologic sequelae (11 cases). Neurologic sequelae occurred most frequently in comatose patients (45.5%) and least often in mentally alert patients (6.1%), more frequently m patients exposed to CO gas for more than 8 hours than in those exposed for less than 8 hours, and in patients who did not receive hyperbaric oxyen therapy(29.4%) than in those who did(19.6%). Delayed neurologic sequelae were mental retardation (72.7%), epilepsy (36.4%), mutism (18.2%) etc. The lucid interval in 11 cases of delayed neurologic sequelae ranged from 2 to 20 days. The results of this study suggest that every patient exposed to CO gas should receive prompt and efficient oxygenation including hyperbaric oxygen therapy and that expeditious reduction of cerebral edema maybe of value. The importance of providing follow-up facilities in anticipation of a relapse of the delayed neurologic sequelae has been established.

Estudo das manifestaçöes neurológicas em 93 doentes com intoxicaçäo exógena por substâncias químicas näo medicamentosas / Neurologic manifestations in 93 patients with exogenous poisoning due to non-medicamentous chemical substances

Foram analisadas as manifestaçöes neurológicas em 93 doentes com suspeita de intoxicaçäo exógena. A detecçäo das substâncias tóxicas foi realizada no sangue, urina e líquido cefalorraqueano. Verificou-se nítido predomínio do comprometimento do sistema nervoso central em relaçäo ao periférico e aparente tropismo de herbicidas e organofosforados para o sistema nervoso central, comparando-se o comportamento dos metais pesados e organoclorados. Säo analisadas os prováveis mecanismos de açäo dessas substâncias no sistema nervoso e säo apresentados o sinais e/ou sintomas que foram observados