Anti-hyperuricemia activity and its mechanism of flavonoid extract from saffron floral bio-residues / 中国中药杂志

A hyperuricemic rat model induced by adenine and ethambutol was established to investigate the anti-hyperuricemia activity and its mechanism of the flavonoid extract from saffron floral bio-residues. Sixty-seven SD rats were randomly divided into control group, model group, positive control group, and flavonoid extract groups(with 3 doses), respectively, and each group contained 11 or 12 rats. The hyperuricemic model was established by continuous oral administration of adenine(100 mg·kg~(-1)) and ethambutol(250 mg·kg~(-1)) for 7 days. At the same time, the positive control group was given allopurinol(20 mg·kg~(-1) per day) and the flavonoid extract groups were given the flavonoid extract at doses of 340, 170 and 85 mg·kg~(-1) per day, respectively. On day 8, rat serum, liver, kidney, and intestinal tissues were collected, and the levels of uric acid in serum and tissue, the xanthine oxidase activities and antioxi-dant activities in serum and liver were evaluated, and the kidney histopathology was explored. In addition, an untargeted serum metabolomics study was performed. According to the results, the flavonoid extract effectively reduced the uric acid levels in serum, kidney and ileum and inhibited the xanthine oxidase activities and elevated the antioxidant activities of serum and liver in hyperuricemic rat. At the same time, it reduced the levels of inflammation factors in kidney and protected renal function. Moreover, 68 differential metabolites of hyperuricemic rats were screened and most of which were lipids and amino acids. The flavonoid extract significantly retrieved the levels of differential metabolites in hyperuricemic rats, such as SM(d18:1/20:0), PC[18:0/18:2(92,12Z)], palmitic acid and citrulline, possibly through the following three pathways, i.e., arginine biosynthesis, glycine, serine and threonine metabolism, and histidine metabolism. To sum up, the flavonoid extract of saffron floral bio-residues lowered the uric acid level, increased the antioxidant activity, and alleviated inflammatory symptoms of hyperuricemic rats, which may be related to its inhibition of xanthine oxidase activity and regulation of serum lipids and amino acids metabolism.

Neuropatía óptica severa por etambutol / Severe optic neuropathy by ethambutol

Un varón de 51 años de edad con antecedentes de tuberculosis (TB) pulmonar en el año 2000, tratado por régimen 2RHZE/4RH. Presentó una recurrencia de TB con baciloscopía positiva y sensible a la rifampicina (Figura 1). Recibió etambutol (15 mg/kg/día), isoniacida (300 mg/día), rifampicina (600 mg/día) y pirazinamida (25mg/Kg/ día), más piridoxina 150 mg/ día. Tres meses después, el paciente presentó pérdida de la agudeza visual (AV) en ambos ojos (AO): 1/10 ojo derecho y 2/10 ojo izquierdo.

Drug-induced Hepatotoxicity of Anti-tuberculosis Drugs and Their Serum Levels

The correlation between serum anti-tuberculosis (TB) drug levels and the drug-induced hepatotoxicity (DIH) remains unclear. The purpose of this study was to investigate whether anti-TB DIH is associated with basal serum drug levels. Serum peak levels of isoniazid (INH), rifampicin (RMP), pyrazinamide (PZA), and ethambutol (EMB) were analyzed in blood samples 2 hr after the administration of anti-TB medication. Anti-TB DIH and mild liver function test abnormality were diagnosed on the basis of laboratory and clinical criteria. Serum anti-TB drug levels and other clinical factors were compared between the hepatotoxicity and non-hepatotoxicity groups. A total of 195 TB patients were included in the study, and the data were analyzed retrospectively. Seventeen (8.7%) of the 195 patients showed hepatotoxicity, and the mean aspartate aminotransferase/alanine aminotransferase levels in the hepatotoxicity group were 249/249 IU/L, respectively. Among the 17 patients with hepatotoxicity, 12 showed anti-TB DIH. Ten patients showed PZA-related hepatotoxicity and 2 showed INH- or RMP-related hepatotoxicity. However, intergroup differences in the serum levels of the 4 anti-TB drugs were not statistically significant. Basal serum drug concentration was not associated with the risk anti-TB DIH in patients being treated with the currently recommended doses of first-line anti-TB treatment drugs.

Drug-induced Hepatotoxicity of Anti-tuberculosis Drugs and Their Serum Levels

The correlation between serum anti-tuberculosis (TB) drug levels and the drug-induced hepatotoxicity (DIH) remains unclear. The purpose of this study was to investigate whether anti-TB DIH is associated with basal serum drug levels. Serum peak levels of isoniazid (INH), rifampicin (RMP), pyrazinamide (PZA), and ethambutol (EMB) were analyzed in blood samples 2 hr after the administration of anti-TB medication. Anti-TB DIH and mild liver function test abnormality were diagnosed on the basis of laboratory and clinical criteria. Serum anti-TB drug levels and other clinical factors were compared between the hepatotoxicity and non-hepatotoxicity groups. A total of 195 TB patients were included in the study, and the data were analyzed retrospectively. Seventeen (8.7%) of the 195 patients showed hepatotoxicity, and the mean aspartate aminotransferase/alanine aminotransferase levels in the hepatotoxicity group were 249/249 IU/L, respectively. Among the 17 patients with hepatotoxicity, 12 showed anti-TB DIH. Ten patients showed PZA-related hepatotoxicity and 2 showed INH- or RMP-related hepatotoxicity. However, intergroup differences in the serum levels of the 4 anti-TB drugs were not statistically significant. Basal serum drug concentration was not associated with the risk anti-TB DIH in patients being treated with the currently recommended doses of first-line anti-TB treatment drugs.

Desfechos clínicos do tratamento de tuberculose utilizando o esquema básico recomendado pelo Ministério da Saúde do Brasil com comprimidos em dose fixa combinada na região metropolitana de Goiânia / Clinical treatment outcomes of tuberculosis treated with the basic regimen recommended by the Brazilian National Ministry of Health using fixed-dose combination tablets in the greater metropolitan area of Goiânia, Brazil

OBJETIVO: Descrever as taxas de cura, falência e abandono do tratamento da tuberculose com o esquema básico preconizado pelo Ministério da Saúde (tratamento com rifampicina, isoniazida, pirazinamida e etambutol por dois meses seguido de isoniazida e rifampicina por quatro meses) utilizando comprimidos em dose fixa combinada em regime autoadministrado e descrever os eventos adversos e seus possíveis impactos nos desfechos do tratamento. MÉTODOS: Estudo descritivo utilizando dados coletados prospectivamente dos prontuários médicos de pacientes com tuberculose (idade > 18 anos) tratados com o esquema básico em duas unidades básicas de saúde da região metropolitana de Goiânia, GO. RESULTADOS: A amostra foi composta por 40 pacientes com tuberculose. A taxa de cura foi de 67,5%, a taxa de abandono foi de 17,5%, e não ocorreram casos de falência. Nessa amostra, 19 pacientes (47%) relataram reações adversas aos medicamentos. Essas foram leves e moderadas, respectivamente, em 87% e 13% dos casos. Em nenhum caso houve necessidade de mudança do esquema ou suspensão do tratamento. CONCLUSÕES: A taxa de cura do esquema básico com o uso de comprimidos em dose fixa combinada sob regime autoadministrado foi semelhante às taxas históricas do esquema anterior. A taxa de abandono, na amostra estudada, foi muito acima da taxa preconizada como adequada (até 5%).

OBJECTIVE: To describe the rates of cure, treatment failure, and treatment abandonment obtained with the basic regimen recommended by the Brazilian National Ministry of Health (rifampin, isoniazid, pyrazinamide, and ethambutol for two months, followed by isoniazid and rifampin for four months) involving the use of fixed-dose combination tablets (self-administered treatment), as well as to describe adverse events and their potential impact on treatment outcomes. METHODS: This was a descriptive study based on prospective data obtained from the medical records of tuberculosis patients (> 18 years of age) treated with the basic regimen at either of two primary health care facilities in the greater metropolitan area of Goiânia, Brazil. RESULTS: The study sample comprised 40 tuberculosis patients. The rate of cure was 67.5%, the rate of treatment abandonment was 17.5%, and there were no cases of treatment failure. Of the 40 patients in the sample, 19 (47%) reported adverse reactions, which were mild and moderate, respectively, in 87% and 13% of the cases. It was not necessary to alter the regimen or discontinue the treatment in any of the cases evaluated. CONCLUSIONS: The rate of cure obtained with the self-administered, fixed-dose combination tablet form of the new basic regimen was similar to the historical rates of cure obtained with the previous regimen. The rate of treatment abandonment in our sample was much higher than that considered appropriate (up to 5%).

Tratamiento directamente observado de la tuberculosis en un hospital de la Ciudad de Buenos Aires / Directly observed treatment for tuberculosis in a Buenos Aires City hospital

Se describe la experiencia en la aplicación del tratamiento directamente observado de tuberculosis (TDO) en el período 1/1/1979-31/12/2009 y la comparación de los resultados obtenidos en el periodo 1979-1999 versus los de 2000- 2009. En un hospital de la Ciudad de Buenos Aires, 582 pacientes HIV negativos recibieron inicialmente rifampicina, isoniazida, pirazinamida y etambutol o estreptomicina. En la segunda fase 424 de estos pacientes tratados entre 01/01/1979 y 31/12/1999 (G1), recibieron esquemas bisemanales con rifampicina/isoniazida o isoniazida/estreptomicina y otros 158 pacientes, tratados entre 01/01/2000 y 31/12/2009 (G2) recibieron un esquema bisemanal o trisemanal con rifampicina/isoniazida. Se siguieron las recomendaciones de los programas de control de la Nación y la Ciudad. Los pacientes bajo TDO tuvieron tasas de tratamiento completo más elevadas (82.8% versus 48.7%), (p < 0.0001) con respecto a otros 483, que siguieron tratamiento autoadministrado (AUTO); la edad promedio fue de 36.3 ± 15.3 años, 63.1% eran varones y 69.4% tenían nacionalidad argentina. Presentaron tratamiento previo el 8.9%, comorbilidades el 6.1% y el 70.6% de las formas pulmonares fueron confirmadas bacteriológicamente. El 9.5% presentó efectos adversos a drogas y el sexo masculino presentó mayor frecuencia de abandonos (p = 0.004). Con respecto al G1, en el G2 hubo menor proporción de pacientes argentinos (48.7% vs. 77.1%), (p ≤ 0.0001), mayor frecuencia de comorbilidades (10.7% vs. 4.4%), (p = 0.005), de formas clínicas pulmonares con confirmación bacteriológica (95% vs. 87%), (p = 0.02) y de efectos adversos a drogas (17% vs. 6.6%), (p ≤ 0.0001). Hallamos tasas de cumplimiento total elevadas en TDO (82.8%), similares a las otras publicaciones.

The outcomes of directly observed therapy of tuberculosis (DOT) between 1/1/1979 and 12/31/2009 were analyzed. Results obtained in the 1979-1999 period were compared with those achieved in the 2000-2009 period. In a Buenos Aires City hospital, 582 HIV negative TB patients received rifampin, isoniazid, pyrazinamide and ethambutol or streptomycin in the initial stage, followed by a second stage where patients were included in two groups: G1 composed by 424 patients (period 1/1/1979-12/31/1999) who received either rifampin and isoniazid or rifampin and streptomicin twice a week, and G2, with 158 patients (period 1/1/2000-12/31/2009) who received either rifampin and isoniazid twice or three times a week. National and Buenos Aires City TB Control Programs recommendations were followed. Patients who underwent DOT had higher completeness rates than those included in self-administered therapy (82.8% vs. 48.7%), (p <0.0001). Mean age: 36.3±15.3 years, males: 63.1% and 69.4% were Argentine citizens. A 8.9% had been previously treated, 6.1% had co-morbidities. A 70.6% of pulmonary cases was bacteriologically confirmed, 82.8% of them completed the treatment, while 11.5% defaulted. Adverse effects to antituberculosis drugs were observed in 9.5% of cases; male patients showed higher rates of non adherence. G2 had a lower proportion of native people (48.7% vs. 77.1%), (p ≤ 0.0001), higher frequency of co-morbidities (10.7% vs. 4.4%), (p = 0.005), of bacteriologically confirmed pulmonary cases (95% vs. 87%), (p = 0.02) and more adverse effects than G1 (17% vs. 6.6%), (p ≤ 0.0001). In coincidence with other experiences, this work shows high treatment success rates in patients treated under DOT strategy.

Resposta paradoxal após o início de tratamento para tuberculose: relato de caso / Paradoxical response after initiation of tuberculosis treatment: case report

JUSTIFICATIVA E OBJETIVOS: A reação paradoxal pode ser identificada em até 30% de todos os pacientes após o início de tratamento para tuberculose, embora seu diagnóstico permaneça um desafio, já que não existem testes confiáveis que o corroborem. O objetivo deste estudo foi relatar um caso em que o diagnóstico de reação paradoxal foi realizado.RELATO DO CASO: Paciente do sexo masculino, 31 anos,um mês após o início de uso de fármacos para tratamento de tuberculose miliar, com diagnóstico realizado por lavado broncoalveolar, apresentou plegia no membro inferior direito, parestesia no membro superior direito e membro inferior esquerdo, incontinência urinária e fecal. Ressonância nuclear magnética do encéfalo evidenciou múltiplas áreas com hipersinal em T2, predominando em substância branca subcortical em ambos os hemisférios, com realce de lesões nodulares, sugestivas de infecção oportunista. Antivírus da imunodeficiência humana 1/2 foi negativo. PCR DNA para M. tuberculosis no líquor foi negativa. Iniciou-se, então, dexametasona. O paciente apresentou melhora significativa, porém permaneceu com incontinência urinária.Tomografia computadorizada de crânio realizada posteriormente não evidenciou quaisquer alterações. CONCLUSÃO: Apesar de sua elevada prevalência, continua difícilr ealizar o diagnóstico de reação paradoxal após o início de tratamento para tuberculose. Mais estudos são necessários para melhor definir os parâmetros diagnósticos e para orientar diretrizes terapêuticas mais efetivas.

BACKGROUND AND OBJECTIVES: Paradoxical response can be identified in up to 30% of all patients after initiation of tuberculosis treatment, although your diagnosis still remains a challenge, mainly because do not exist trustworthy tests to confirm it. These study aimed to describe a case were the diagnosis of a paradoxical response was made.CASE REPORT: Male patient, 31 year-old, a month after the initiation of miliary tuberculosis treatment, with the diagnosis realized by bronchoalveolar lavage, presented right lower limb plegia, right upper limb paresthesia, urge and fecal incontinence. Brain Magnetic Resonance Imaging evidenced hyper signs of T2 in multiple areas, in which predominated in white subcortical substance, beyond enhancing nodular lesions, suggesting an opportunistic infection. Anti human immunodeficiency virus 1/2 was negative. PCR DNA to M. tuberculosis in liquor was negative. After, dexamethasone treatment was started. The patient presented a significant improvement, but urge incontinence remained unchanged. Brain computed tomography realized after not evidence any alteration. CONCLUSION: Despite paradoxical response presents high occurrence, it continuous to be difficult to make the diagnosis of paradoxical response after initiation of tuberculosis treatment. Further studies are necessary in order to improve the diagnostic parameters and to orientate more effective therapeutic consensus.

Preditores dos desfechos do tratamento da tuberculose / Predictors of tuberculosis treatment outcomes

OBJETIVO: Analisar os desfechos do tratamento da tuberculose e seus preditores. MÉTODOS: Estudo longitudinal de coorte de pacientes com tuberculose tratados entre 2004 e 2006 no Instituto de Pesquisa Evandro Chagas, na cidade do Rio de Janeiro. As razões de risco ajustadas (RRa) dos preditores foram estimadas. RESULTADOS: Foram incluídos 311 pacientes. As taxas de cura, de abandono, de mortalidade e de falha terapêutica foram, respectivamente, 72 por cento, 19 por cento, 6 por cento e 2 por cento. A troca de regime terapêutico por eventos adversos foi necessária em 8 por cento. O alcoolismo (RRa, 0,30), uso do regime estreptomicina+etambutol+ofloxacina (SEO; RRa, 0,32), infecção por HIV sem tratamento antirretroviral (TARV; RRa, 0,36) e o uso do regime rifampicina+isoniazida+pirazinamida+etambutol (RRa, 0,58) reduziram a probabilidade de cura. A faixa etária mais jovem (RRa, 3,84) e o alcoolismo (RRa, 1,76) aumentaram a probabilidade do abandono. Não foi possível determinar as RRa para os demais desfechos devido a suas baixas prevalências. Entretanto, medidas do risco relativo (RR) identificaram os seguintes potenciais preditores do óbito: uso de esquema SEO (RR, 11,43), infecção pelo HIV sem TARV (RR, 9,64), forma clínica disseminada (RR, 9,09), ausência de confirmação bacteriológica (RR, 4,00), diabetes mellitus (RR, 3,94) e comportamento homo/bissexual (RR, 2,97). A baixa renda (RR, 11,70) foi potencial preditor para falha terapêutica, ao passo que infecção pelo HIV com uso de TARV (RR, 2,46) e forma clínica disseminada (RR, 3,57) foram potenciais preditores para troca do esquema por evento adverso. CONCLUSÕES: O esquema SEO deve ser utilizado transitoriamente quando possível. Os dados confirmam a importância de TARV e sugerem a necessidade de seu início precoce.

OBJECTIVE: To analyze tuberculosis treatment outcomes and their predictors. METHODS: This was a retrospective longitudinal cohort study involving tuberculosis patients treated between 2004 and 2006 at the Instituto de Pesquisa Evandro Chagas, in the city of Rio de Janeiro. We estimated adjusted risk ratios (ARRs) for the predictors of treatment outcomes. RESULTS: Among 311 patients evaluated, the rates of cure, treatment abandonment, treatment failure, and mortality were 72 percent, 19 percent, 2 percent, and 6 percent, respectively. Changes in the treatment regimen due to adverse events occurred in 8 percent. The factors found to reduce the probability of cure were alcoholism (ARR, 0.30), use of the streptomycin+ethambutol+ofloxacin (SEO) regimen (ARR, 0.32), HIV infection without the use of antiretroviral therapy (ART; ARR, 0.36), and use of the rifampin+isoniazid+pyrazinamide+ethambutol regimen (ARR, 0.58). Being younger and being alcoholic both increased the probability of abandonment (ARR, 3.84 and 1.76, respectively). It was impossible to determine the ARR for the remaining outcomes due to their low prevalence. However, using the relative risk (RR), we identified the following potential predictors of mortality: use of the SEO regimen (RR, 11.43); HIV infection without ART (RR, 9.64); disseminated tuberculosis (RR, 9.09); lack of bacteriological confirmation (RR, 4.00); diabetes mellitus (RR, 3.94); and homosexual/bisexual behavior (RR, 2.97). Low income was a potential predictor of treatment failure (RR, 11.70), whereas disseminated tuberculosis and HIV infection with ART were potential predictors of changes in the regimen due to adverse events (RR, 3.57 and 2.46, respectively). CONCLUSIONS: The SEO regimen should not be used for extended periods. The data confirm the importance of ART and suggest the need to use it early.

Desfechos do retratamento de pacientes com tuberculose com o uso do esquema 3 em Porto Alegre, Brasil / Retreatment of tuberculosis patients in the city of Porto Alegre, Brazil: outcomes

OBJETIVO: Descrever os desfechos do retratamento de pacientes com tuberculose com o uso do esquema 3 (estreptomicina, etambutol, etionamida e pirazinamida por 3 meses + etambutol e etionamida por 9 meses) devido à falência do tratamento com o esquema básico (rifampicina, isoniazida e pirazinamida por 2 meses + rifampicina e isoniazida por 4 meses). MÉTODOS: Estudo descritivo de coorte histórica, não controlada, com adultos que foram tratados com o esquema 3. Foram avaliados os desfechos desse tratamento, as reações adversas aos fármacos, as recidivas e os fatores associados. RESULTADOS: Foram incluídos no estudo 229 pacientes. A taxa de cura geral foi de 62 por cento. Entre os pacientes que usaram a medicação regularmente e aqueles que a usaram irregularmente, a taxa de cura foi de 88 por cento e 31 por cento, respectivamente. Observaram-se reações adversas em 95 pacientes (41,5 por cento), principalmente digestivas. Ocorreram 17 recidivas (12,0 por cento) nos cinco anos de seguimento. CONCLUSIONS: Os desfechos com o uso do esquema 3, em geral, não foram satisfatórios, pois esse esquema foi aplicado em uma população selecionada com alto risco de não adesão ao tratamento e apresenta altas taxas de reações adversas, especialmente as de tipo digestivo, possivelmente causadas pela etionamida. No entanto, para aqueles que conseguiram tomar a medicação regularmente, a taxa de cura foi satisfatória. A taxa de recidiva foi superior àquela preconizada por consensos internacionais, possivelmente devido ao tempo de tratamento curto (apenas 12 meses). Acreditamos que o esquema 3 estendido para 18 meses poderia ser uma alternativa para pacientes com comprovada adesão ao tratamento.

OBJECTIVE: To describe the outcomes of retreatment in tuberculosis patients receiving the regimen known, in Brazil, as regimen 3 (streptomycin, ethambutol, ethionamide, and pyrazinamide for 3 months + ethambutol and ethionamide for 9 months) after treatment failure with the basic regimen (rifampin, isoniazid, and pyrazinamide for 2 months + rifampin and isoniazid for 4 months). METHODS: A descriptive, uncontrolled, historical cohort study involving adult tuberculosis patients treated with regimen 3. We evaluated adverse drug effects, recurrence, treatment outcomes, and associated factors. RESULTS: The study included 229 patients. The overall cure rate was 62 percent. For the patients who used the medications regularly and those who did not, the cure rate was 88 percent and 31 percent, respectively. Adverse events occurred in 95 patients (41.5 percent), and most of those events were related to the gastrointestinal tract. In the five-year follow-up period, relapse occurred in 17 cases (12.0 percent). CONCLUSIONS: Overall, the outcomes of treatment with regimen 3 were unsatisfactory, in part because this regimen was administered to a selected population of patients at high risk for noncompliance with treatment, as well as because it presents high rates of adverse effects, especially those related to the gastrointestinal tract, which might be caused by ethionamide. However, for those who took the medications regularly, the cure rate was satisfactory. The recurrence rate was higher than that recommended in international consensus guidelines, which might be attributable to the short (12-month) treatment period. We believe that regimen 3, extended to 18 months, represents an option for patients with proven treatment compliance.

Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) Syndrome Induced by Celecoxib and Anti-tuberculosis Drugs

Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) syndrome reflects a serious hypersensitivity reaction to drugs, characterized by skin rash, fever, lymph node enlargement, and internal organ involvement. So far, numerous drugs such as sulfonamides, phenobarbital, sulfasalazine, carbamazepine, and phenytoin have been reported to cause the DRESS syndrome. We report a case in a 29-yr-old female patient who had been on celecoxib and anti-tuberculosis drugs for one month to treat knee joint pain and pulmonary tuberculosis. Our patient's clinical manifestations included fever, lymphadenopathy, rash, hypereosinophilia, and visceral involvement (hepatitis and pneumonitis). During the corticosteroid administration for DRESS syndrome, swallowing difficulty with profound muscle weakness had developed. Our patient was diagnosed as DRESS syndrome with eosinophilic polymyositis by a histopathologic study. After complete resolution of all symptoms, patch tests were positive for both celecoxib and ethambutol. Although further investigations might be needed to confirm the causality, celecoxib and ethambutol can be added to the list of drugs as having the possibility of DRESS syndrome.

Tuberculous ulcer of tongue with oral complications of oral antituberculosis therapy.

Tuberculosis (TB) is an infectious disease affecting humans of all ages in all parts of the world. The dentist plays an important role in the identification and control of this condition by early recognition of oral lesions that may precede the detection of the pulmonary form. Occurrence of increased incidence of mycobacterial infections as a part of the spectrum of AIDS only emphasizes the importance of early diagnosis. A case of a tuberculous ulcer on the tongue along with oral ulcerations, which occurred as a consequence of oral antituberculosis therapy (ATT), is presented. Such complications have rarely been reported in the literature and the management of these is described herein. The tuberculous ulcer healed uneventfully in five weeks after institution of ATT and the other ATT-induced ulcers healed after a week of topical anesthetic application. The clinical presentations, differential diagnoses to be considered, and management of such oral manifestations is discussed. The occupational risk posed by TB to the dentist and appropriate precautions to be observed have been highlighted.

Efficacy of PS-VEPS in the detection of subclinical optic neuritis following ethambutol in therapeutic dosage

Ethambutol is an antimicrobial agent used frequently to treat tuberculosis. The most commonly recognized toxic effect of ethambutol is optic neuropathy, which may sometime result in irreversible vision loss. However, early recognition not only prevents this complication, it also increases compliance of the drug. This study was carried out to assess the usefulness of pattern-shift visual evoked potentials [PS-VEPs] in the detection of sub clinical optic neuropathy in patients on ethambutol for the treatment of tuberculosis in the recommended dosage. 30 consecutive patients of tuberculosis were studied before and after two months of ethambutol therapy. Ethambutol was administered in the WHO recommended dosage of 15mg/kg of body weight. All the patients underwent pattern shift visual evoked potential tests, which check the function of the visual pathway from the retina to the occipital cortex. PS-VEP abnormalities were seen in 5 patients [16.7%],out of which prolonged latency was documented in 3 patients [10%],increased latency difference was seen in 1 patient [3.3%] and abnormal amplitude difference was reported in 1 patient [3.3%].Associated psychophysical abnormalities of visual acuity in 2 patients [6.7%] and color vision abnormality in 1 patient [3.3%] were also seen. Our study confirms that during the treatment with ethambutol, PS-VEPs may reveal a surprisingly high percentage of sub clinical optic neuritis even at dosages considered to be safe. This needs attention in terms of patient care and drug compliance

Rapidly developing Optic Neuritis secondary to Ethambutol: possible mechanism of injury

Optic neuritis has been described among the toxic effects of Ethambutol. This side effect is dose related. The mean duration of Ethambutol induced optic neuritis [EON] is three months. We report a case of EON after few days of exposure to Ethambutol and the symptoms resolved after discontinuation of Ethambutol. This most likely represents an idiosyncratic reaction which is different as compared to dose related optic neuritis

Evaluation of visual functions in patients on ethambutol therapy for tuberculosis: a prospective study.

To study the incidence of clinical and subclinical optic nerve toxicity with ethambutol therapy in patients with tuberculosis and to evaluate the reversibility of its side effects after cessation of therapy. This prospective randomized controlled study included 60 newly diagnosed adult cases of tuberculosis, who were randomly assigned into two groups. The study group included 30 patients (60eyes) who received ethambutol as a part of their anti-tubercular treatment and the control group included 30 patients (60eyes) who did not receive ethambutol. The patients were examined on monthly basis. The visual parameters studied were best corrected visual acuity, pupillary reactions, optic disc changes, color vision, contrast sensitivity, pupil cycle time, visual field charting and visual evoked potential. Ethambutol was stopped in those patients in whom toxicity was detected and they were followed more frequently. Only one patient (3.3%) showed decrease in visual acuity, three patients (10%) developed visual field defects, two patients (6.7%) showed deterioration of contrast sensitivity, the pupil cycle time was prolonged in one eye and two patients (6.7%) showed abnormal visual evoked potential. During the therapy, all patients in the study group had normal pupillary reactions, fundus picture and color vision. Conclusions: Ethambutol induced ocular toxicity was seen in three patients (10%) in our study. The maximum visual recovery occurred in first six to eight weeks after stopping ethambutol. The visual recovery was complete in only one patient, but it was partial in two patients i.e. visual fields, contrast sensitivity and visual evoked potential remained abnormal.

Ethambutol and optic neuropathy.

PURPOSE: To demonstrate the association between ethambutol and optic neuropathy. METHOD: Thirteen patients who developed optic neuropathy after being treated with ethambutol for tuberculosis of the lung or lymph node at Siriraj Hospital between 1997 and 2001 were retrospectively reviewed. The clinical characteristics and initial and final visual acuity were analyzed to determine visual outcome. RESULTS: All patients had optic neuropathy between 1 to 6 months (mean = 2.9 months) after starting ethambutol therapy at a dosage ranging from 13 to 20 mg/kg/day (mean = 17 mg/kg/day). Seven (54%) of the 13 patients experienced visual recovery after stopping the drug. Of 6 patients with irreversible visual impairment, 4 patients had diabetes mellitus, glaucoma and a history of heavy smoking. CONCLUSION: Early recognition of optic neuropathy should be considered in patients with ethambutol therapy. A low dose and prompt discontinuation of the drug is recommended particularly in individuals with diabetes mellitus, glaucoma or who are heavy smokers.

Effect of ethambutol on the development of the retina and optic nerve of the chick embryo

The present work was concerned with the development of the retina and optic nerve of the chick embryo and the effect of ethambutol on its development together with the explanation of the possible hazards of antituberculous drugs which May occur To the foetus, if the pregnant mother is under the treatment with these drugs. Histological studies were made on the retina and optic nerve of 9,11 and 15 days chick embryos injected on the 6 th day of incubation with a dose of ethambutol equivalent to the human therapeutic dose [0.8mg/chick embryo]. It was found that ethambutol induced retardation of growth and degenerative changes in the layers of the retina associated with reduction in the size of the optic nerve. As age advenced at 15 day of incubation, regeneration of retina started and progressed gradually till full term, but its size was still less than the control embryo of the same age

Visual evoked responses in ethambutol induced optic neuritis.

Pattern evoked responses were recorded in 46 patients of tuberculosis on ethambutol and 16 healthy subjects. Deterioration in visual acuity was documented in two patients (4.3%). P100 latency was delayed in 16 cases (34.8%), while in 12 patients (26.1%) both latency and amplitude were affected. A cut off latency value of > or = 140 ms was associated with ophthalmological findings. The incidence of subclinical toxicity as detected by visual evoked response (VER) was higher in older subjects, patients on higher doses of ethambutol (> or = 20 mg/kg/day) and longer duration of treatment. Of two cases with objective ocular signs, one who reported for follow up after two months had recovered completely after stopping ethambutol. Recording of VER is an extremely useful objective test for subclinical optic nerve damage.

Visual evoked responses in tuberculous children on ethambutol therapy.

Visual evoked responses (VERs) were recorded in 47 children, aged 3-13 years with tuberculosis, treated with ethambutol (20 mg/kg/day) as a part of the antitubercular regimen. VERs were evoked by monocular whole field stimulation, the stimulus being provided by a black and white checker-board pattern reversed every 560 msec and recorded before the commencement, 2, 4, 6, 9 and 12 months of therapy and between 3 to 6 months after stopping the drug. In the first 6 months of therapy the mean values of latency ranged from 92.8 to 101.3 msec in the 3 to less than 6 years age group and 88.5 to 100.3 msec in children 6-13 years of age. Between 6-12 months of therapy the mean values of latency were between 93.3 to 101.0 msec in the 3 to less than 6 years age group and 96.0 to 101.5 msec in the older group. Between 3-6 months after stopping therapy the means of latency ranged from 92 to 96 msec. The differences were not statistically significant at any point of time. Thus, children do not seem to be at greater risk for developing ethambutol inducted optic damage as compared to adults. Ethambutol in the above stated dose may, therefore, be recommended for inclusion in antitubercular chemotherapy in pediatrics without undue fear of subclinical toxicity.