Another record of significant regional variation in toxicity of Tityus serrulatus venom in Brazil: a step towards understanding the possible role of sodium channel modulators.

The scorpion Tityus serrulatus is responsible for the most severe accidents that have been registered in Brazil, mainly in the state of Minas Gerais (MG), being the lung edema (LE), the main cause of death in these accidents. Although an increased in the number of accidents caused to this species in Federal District (Distrito Federal - DF), it seems that this particular species is not responsible for severe scorpionism cases in this region. Given this observation, we tested the toxicity in mice and compared the ability of T. serrulatus venom from DF (Ts-DF) and Minas Gerais State (Ts-MG) to induce LE in rats. The LD50 of Ts-DF venom was 51.6 µg/mouse, almost twice (1.98) higher than that obtained for Ts-MG venom. The ability of venom (0.5 mg/kg) to induce LE in rats was determined by the wet weight differences between treated and untreated lungs, by pulmonary morphological analyses and by pulmonary vascular permeability (PVP) using the Evans blue protocol. Significant differences in the wet weight of lungs and changes in PVP were found in Ts-MG venom treated rats when compared to rats treated with Ts-DF venom or untreated rats (p < 0.001), but no differences occurred when comparing rats treated with Ts-DF venom and untreated rats (p < 0.05). These results were confirmed by evaluation of pulmonary morphology. Comparison of chromatographic profiles obtained from these venoms (Ts-DF and Ts-MG) using the fractal dimension (D) analysis and the molecular mass fingerprint of the chromatographic fractions showed a higher number of components between 35 and 40% acetonitrile in Ts-MG venom than in Ts-DF venom, indicating a higher diversity of sodium channel modulators in that venom.

Pneumotoxicosis in sheep caused by ingestion of trema micrantha.

Trema micrantha, a fast-growing tree distributed throughout the Americas, produces palatable leaves that have been associated with hepatic necrosis and acute death when consumed by livestock. This report describes fatal pulmonary disease of sheep triggered by consumption of Trema micrantha. Affected sheep had severe progressive dyspnea for a few days before death. Subcutaneous and mediastinal emphysema, reddened lungs, interalveolar septal thickening, and diffuse type II pneumocyte proliferation were the main pathological findings. After ingesting 77.5 and 102.5 g/kg (divided in 3 doses, at 30-day intervals) of T. micrantha leaves, 2 additional sheep developed the same condition. These findings indicate that T. micrantha toxicosis should be considered in the differential diagnosis of ovine respiratory disease.

Impaired lung function in individuals chronically exposed to biomass combustion.

BACKGROUND: The use of biomass for cooking and heating is considered an important factor associated with respiratory diseases. However, few studies evaluate the amount of particulate matter less than 2.5 µm in diameter (PM2.5), symptoms and lung function in the same population. OBJECTIVES: To evaluate the respiratory effects of biomass combustion and compare the results with those of individuals from the same community in Brazil using liquefied petroleum gas (Gas). METHODS: 1402 individuals in 260 residences were divided into three groups according to exposure (Gas, Indoor-Biomass, Outside-Biomass). Respiratory symptoms were assessed using questionnaires. Reflectance of paper filters was used to assess particulate matter exposure. In 48 residences the amount of PM2.5 was also quantified. Pulmonary function tests were performed in 120 individuals. RESULTS: Reflectance index correlated directly with PM2.5 (r=0.92) and was used to estimate exposure (ePM2.5). There was a significant increase in ePM2.5 in Indoor-Biomass and Outside-Biomass, compared to Gas. There was a significantly increased odds ratio (OR) for cough, wheezing and dyspnea in adults exposed to Indoor-Biomass (OR=2.93, 2.33, 2.59, respectively) and Outside-Biomass (OR=1.78, 1.78, 1.80, respectively) compared to Gas. Pulmonary function tests revealed both Non-Smoker-Biomass and Smoker-Gas individuals to have decreased %predicted-forced expiratory volume in the first second (FEV1) and FEV1/forced vital capacity (FVC) as compared to Non-Smoker-Gas. Pulmonary function tests data was inversely correlated with duration and ePM2.5. The prevalence of airway obstruction was 20% in both Non-Smoker-Biomass and Smoker-Gas subjects. CONCLUSION: Chronic exposure to biomass combustion is associated with increased prevalence of respiratory symptoms, reduced lung function and development of chronic obstructive pulmonary disease. These effects are associated with the duration and magnitude of exposure and are exacerbated by tobacco smoke.

Dyspnoea in patients with chronic hepatitis C treated with pegylated interferon and ribavirin.

BACKGROUND: Adverse events attributed to the treatment of chronic hepatitis C patients with pegylated interferon (PEG-IFN) and ribavirin have been widely discussed. Lung disorders have been described, but the respiratory function of these patients during treatment has not been well studied. The aim of this study was to investigate the incidence of dyspnoea and possible changes in lung function associated with the use of PEG-IFN and ribavirin. METHODS: We evaluated clinical data and spirometry in 31 patients with chronic hepatitis C infections prior to treatment, in the 2(nd) week of treatment and in the 12(th) week of treatment. RESULTS: During the follow-up period, 19 patients (61.3%) had dyspnoea. Decreased haemoglobin levels were observed during the study, but there was no significant association with dyspnoea. However, patients with a body mass index (BMI) greater than 25 had a higher incidence of dyspnoea. No significant difference was detected between the values of forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), or forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC) ratio measured during the investigation. However, a significant decrease in FEV1 and FEV1/FVC ratio was observed in patients with later stages of liver fibrosis. CONCLUSIONS: Dyspnoea is a frequently occurring respiratory symptom during chronic hepatitis C treatment, and it is not associated with changes in spirometric parameters in the first 12 weeks of treatment. However, changes in FEV1 and FEV1/FVC can be observed in patients with advanced liver disease in the first 12 weeks of treatment with PEG-IFN and ribavirin.

Ivermectin-related adverse clinical events in patients treated for Mansonella ozzardi infections.

We report the occurrence of serious reactions after treatment with oral ivermectin in two patients with Mansonella ozzardi infections. Both had systemic and respiratory symptoms and recovered without sequelae. Follow-up revealed clearance of microfilaremia in both cases, with relapse in one of them. These reactions are well described in the treatment of other filarial infections, but have not yet been reported in the treatment of M. ozzardi. We are now reporting the first such known reactions with this helminthiasis.

Poor perception of dyspnea following methacholine challenge test in patients with asthma.

OBJECTIVE: To determine the proportion of asthma patients with a poor perception of dyspnea, correlating the level of that perception with the severity of acute bronchoconstriction, bronchial hyperresponsiveness, use of maintenance medication, and asthma control. METHODS: Uncontrolled clinical trial involving asthma patients treated at the Pulmonology Outpatient Clinic of the São Lucas Hospital, in Porto Alegre , Brazil. Methacholine challenge testing was performed using a five-breath dosimeter protocol. The perception of dyspnea after each breath was determined using the Borg scale. Data concerning asthma control, medication in use, and use of rescue short-acting bronchodilators were recorded. RESULTS: Of the 65 patients included in the study, 53 completed the evaluation. Of those, 32 (60.5%) showed adequate perception of dyspnea after the methacholine challenge test, whereas 21 (39.5%) did not perceive any changes in the degree of dyspnea even after a 20% fall in FEV1. There were no significant differences between the two groups regarding baseline FEV1, percentage fall in FEV1, and the dose of methacholine causing a 20% fall in FEV1. The perception of dyspnea was not significantly associated with age (p = 0.247); gender (p = 0.329); use of maintenance medication (p = 0.152); asthma control (p = 0.562), bronchial hyperresponsiveness (p = 0.082); or severity of acute bronchoconstriction (p = 0.749). CONCLUSIONS: A significant proportion of asthma patients have a poor perception of dyspnea. The factors related to the inability of these patients to identify changes in pulmonary function have not yet been well defined. In order to reduce asthma-related morbidity and mortality, it is essential that this group of patients be identified and counseled.

Baixo grau de percepção da dispneia após teste de broncoprovocação induzida por metacolina em pacientes com asma / Poor perception of dyspnea following methacholine challenge test in patients with asthma

OBJETIVO: Determinar o percentual de asmáticos com má percepção da dispneia, correlacionando-a com gravidade da broncoconstrição aguda, hiper-responsividade brônquica, uso de medicação de manutenção e controle da asma. MÉTODOS: Ensaio clínico não controlado com pacientes asmáticos do Ambulatório de Pneumologia do Hospital São Lucas em Porto Alegre (RS). Foram realizados testes de broncoprovocação com metacolina com protocolo dosimetrado em cinco doses, e foi avaliada a percepção da dispneia após cada dose administrada, utilizando a escala de Borg. Dados sobre controle da asma, medicação em uso e uso de broncodilatador de curta ação de resgate foram coletados. RESULTADOS: Dos 65 pacientes incluídos, 53 completaram a avaliação. Desses, 32 (60,5 por cento) apresentaram percepção adequada da dispneia após o teste de broncoprovocação com metacolina, ao passo que 21 (39,5 por cento) não perceberam nenhuma alteração no grau de dispneia mesmo após uma queda de 20 por cento em VEF1. Não houve diferenças significativas entre os dois grupos em relação a VEF1 basal, percentagem de queda do VEF1 e dose de metacolina causadora de queda de 20 por cento do VEF1. Não houve correlação significativa entre percepção da dispneia e idade (p = 0,247), sexo (p = 0,329), uso de medicação de manutenção (p = 0,152), controle da asma (p = 0,562), hiper-responsividade brônquica (p = 0,082) e gravidade da broncoconstrição aguda (p = 0,749). CONCLUSÕES: Uma percentagem significativa dos asmáticos apresenta baixo grau de percepção da dispneia. Os fatores relacionados com a incapacidade de identificação da modificação da função pulmonar não estão bem definidos. A identificação e a orientação desse grupo de pacientes são fundamentais para a redução de morbidade e mortalidade por asma.

OBJECTIVE: To determine the proportion of asthma patients with a poor perception of dyspnea, correlating the level of that perception with the severity of acute bronchoconstriction, bronchial hyperresponsiveness, use of maintenance medication, and asthma control. METHODS: Uncontrolled clinical trial involving asthma patients treated at the Pulmonology Outpatient Clinic of the São Lucas Hospital, in Porto Alegre , Brazil. Methacholine challenge testing was performed using a five-breath dosimeter protocol. The perception of dyspnea after each breath was determined using the Borg scale. Data concerning asthma control, medication in use, and use of rescue short-acting bronchodilators were recorded. RESULTS: Of the 65 patients included in the study, 53 completed the evaluation. Of those, 32 (60.5 percent) showed adequate perception of dyspnea after the methacholine challenge test, whereas 21 (39.5 percent) did not perceive any changes in the degree of dyspnea even after a 20 percent fall in FEV1. There were no significant differences between the two groups regarding baseline FEV1, percentage fall in FEV1, and the dose of methacholine causing a 20 percent fall in FEV1. The perception of dyspnea was not significantly associated with age (p = 0.247); gender (p = 0.329); use of maintenance medication (p = 0.152); asthma control (p = 0.562), bronchial hyperresponsiveness (p = 0.082); or severity of acute bronchoconstriction (p = 0.749). CONCLUSIONS: A significant proportion of asthma patients have a poor perception of dyspnea. The factors related to the inability of these patients to identify changes in pulmonary function have not yet been well defined. In order to reduce asthma-related morbidity and mortality, it is essential that this group of patients be identified and counseled.

Phenol used as a preservative in Bothrops antivenom induces impairment in leukocyte-endothelial interactions.

The effect of Bothrops antivenom on blocking the disturbances induced by Bothrops jararaca venom in leukocyte-endothelial interactions (LEI) at the microcirculation of the cremaster muscle in mice was evaluated using intravital microscopy. Our findings showed that an i.v. injection of Bothrops antivenom, per se, induced changes in LEI, similar to those induced by an s.c. injection of B. jararaca venom, and that Bothrops antivenom can also induce ephemeral symptoms, such as tremor and dyspnea in mice. These effects were mostly due to phenol used in Bothrops antivenom as a preservative, since animals injected i.v. with a phenol solution, but not with phenol-free Bothrops antivenom, presented those effects on LEI, and also tremor and dyspnea. In addition, phenol-free antivenom abrogated venom-induced changes in LEI parameters. The present data demonstrate that Bothrops antivenom contains antibodies that neutralize toxins of B. jararaca venom that impair LEI, and suggest that the phenol used as a preservative in it can originate some undesired effects.

Dispnéia crônica e alterações funcionais respiratórias em ex-trabalhadores com asbestose avaliados para concessão de benefício / Chronic dyspnea and altered respiratory function in former workers with asbestosis evaluated to determine benefits

INTRODUÇAO: A dispnéia é um sintoma de difícil avaliação, principalmente nas doenças ocupacionais. OBJETIVO: Avaliar a relação entre presença e intensidade de dispnéia crônica, e sua repercussão funcional em ex-trabalhadores com asbestose na avaliação de disfunção e incapacidade. MÉTODO: Escores de dispnéia pelas escalas Medical Research Council modificada, American Medical Association de 1984 e 1993 e Baseline Dyspnea Index foram obtidos em 40 ex-trabalhadores com diagnóstico de asbestose, os quais foram também submetidos a espirometria, medidas da capacidade de difusão pulmonar do monóxido de carbono e testes de exercício cardiopulmonar incremental e submáximo. RESULTADO: Dispnéia esteve presente em 72,5 por cento e 67,5 por cento dos indíviduos de acordo com as escalas do Medical Research Council e American Medical Association de 1984, respectivamente e em apenas 37,5 por cento e 31,6 por cento dos pacientes de acordo com as escalas American Medical Association de 1.993 e Baseline Dyspnea Index. Houve melhor concordância entre as escalas Medical Research Council e American Medical Association de 1993, e American Medical Association de 1984 e American Medical Association de 1993 quando as graduações "ausente" e "leve" foram agrupadas. Não foi observada relação significativa entre dispnéia de acordo com cada uma das escalas e presença de anormalidades funcionais no repouso e/ou exercício. CONCLUSAO: O nível de concordância entre as escalas de dispnéia varia significativamente em indivíduos com asbestose. Há falta de relação dos índices de dispnéia com variáveis que avaliam disfunção respiratória em repouso e exercício.

A importância do reconhecimento precoce da toxicidade pulmonar por amiodarona: a propósito de cinco casos / The importance of early recognizing of pulmonary toxicity by amiodarone: a report of five cases

Amiodarona é um agente antiarrítmico, com reconhecida toxicidade para os pulmões. Tal efeito adverso é geralmente relacionado à dose utilizada e duração da terapia, embora existam relatos de que esses não são os únicos preditores da toxicidade. A partir do atendimento, em um curto intervalo de tempo, de cinco pacientes com toxicidade pulmonar por amiodarona no Serviço de Pneumologia do Hospital São Lucas da PUCRS são revisados os critérios clínicos e diagnósticos de tal situação. Conclui-se pela conveniência de alto índice de suspeição clínica de avaliação, em todos os pacientes em uso da droga, da função pulmonar completa, inclusive com difusão pelo monóxido de carbono. A realização de espirometria convencional e gasometria arterial são úteis somente em casos avançados (AU)

Amiodarone is a commonly used anti-arrhythmic agent, with well-recognized lung toxicity. Such adverse effect is usually related to the dose and duration of the treatment, although there are reports showing that these are not the only predictors of toxicity. Following the occurrence of five cases diagnosed in a short period of time at the Serviço de Pneumologia do Hospital São Lucas da PUCRS, we reviewed clinical criteria and diagnostic procedures to assess such clinical situation. We conclude that is necessary a high clinical suspicion rate and for the need of pulmonary function evaluation, including carbon monoxide diffusion capacity, in all patients using the drug. Spirometry and arterial blood gases are useful only in severe cases (AU)

Allergic reaction after rubber dam placement.

In the last few years allergic reactions to natural rubber latex (NRL) have increased in dental practice affecting both the dental team and patients. Some case reports discuss the potential risks of hypersensitivity to NRL products. An adverse patient reaction after dental rubber dam placement is reported. About 1 min after the isolation of the tooth with a rubber dam the patient presented signs and symptoms of hypersensitivity. Oxygen and intravenous hydrocortisone were administered and the patient kept under observation. After 2 h she had stable vital signs and no more allergics symptoms. It is unclear whether components of the NRL dam or the cornstarch powder incorporated with the rubber dam was responsible for the allergic reaction. Dentists must be aware of the health problem and be prepared for an adequate management in dental practice.

Alveolar lesions induced by systemic administration of cocaine to rats.

In this work, alveolar lesions induced after systemic administration of cocaine (30 mg/kg per day, i.p.) to rats were evaluated both by light microscope analysis for morphological assessment as well as by measurement of the alveolar area as a quantitative index of the alveolar damage. Rats were examined after different times of exposure: 7, 15, 30, 45, 60 and 75 days. The histopathological evaluation of cocaine-treated rats revealed a remarkable thickening in some interalveolar septa, with interstitial hemorrhages, progressive thrombosis and transformation of reticular and elastic fibers into diffuse fibrosis. A significant decrease of the alveolar area was also observed. These findings are indicative of severe changes in capillaries, alveoli and bronchiole after cocaine exposure, which in turn may progressively disrupt the general function of the lungs. Differential mechanisms of systemic toxicity after cocaine exposure are discussed.

Respiratory symptoms, spirometry and chronic occupational paraquat exposure.

OBJECTIVES: A cross-sectional study was conducted to evaluate the relationship between respiratory health and paraquat exposure. METHODS: The study population was selected from among workers at 15 Nicaraguan banana plantations which relied on paraquat for the control of weeds. All the workers were interviewed after they received their job assignment for the day of the survey, and all who reported never having applied paraquat and all who reported more than 2 years of cumulative exposure as applicators of paraquat with knapsack sprayers were invited for medical evaluation. One hundred and thirty-four exposed workers and 152 unexposed workers were administered a questionnaire interview asking about exposure and respiratory symptoms, and they underwent spirometric testing of forced expiratory volume in 1 s (FEV1.0) and forced vital capacity (FVC). RESULTS: In the exposed group 53% reported having experienced a skin rash or burn resulting from paraquat exposure, 25% reported epistaxis, 58% nail damage, and 42% paraquat splashed in the eyes. There was a consistent dose-response relationship between intensity of exposure (as indicated by a history of skin rash or burn) and the prevalence of dyspnea. This relationship was more marked for more severe dyspnea. There was a 3-fold increase in episodic wheezing accompanied by shortness of breath among the more intensely exposed workers. There was no relationship between exposure and FEV1.0 or FVC. CONCLUSIONS: The high prevalence of respiratory symptoms associated with exposure, in the absence of spirometric abnormalities associated with exposure, could be a result of unmeasured gas exchange abnormalities among workers with long-term exposure to paraquat.

Dapsone in the treatment of dermatitis herpetiformis / ver

The use of dapsone B.P.C. in the treatment of dermatitis herpetiformis is desacribed. 28 cases were treated with excellent control in 24. The toxic effects of the with excellent control in 24 ments for control of treatment are determined. The relative merits of dapsone and sulphapyridine are compared. I wish to tank Dr. G. Harvey for permission to publich these cases and Dr. Baikie for investigating the hematological offects of dapsone.