Síntesis y uso de histidinato de cobre en niños con enfermedad de Menkes en México / Synthesis and use of copper histidinate in children with Menkes disease in Mexico

Resumen La enfermedad de Menkes es una patología neurodegenerativa y letal debida a mutaciones génicas de la enzima ATP-7A trasportadora de cobre; se manifiesta por síntomas neurológicos y alteraciones del tejido conectivo de severidad variable. El uso subcutáneo oportuno de histidinato de cobre (Cu-His) es determinante en la calidad de vida. Se reportan las primeras experiencias en México en la síntesis y uso seguro de Cu-His en tres casos en los que corroboramos hipocupremia e hipoceruloplasminemia. Bajo asesoramiento del Hospital for Sick Children, Toronto, Canadá, elaboramos una solución de 500 µg/mL. En los tres casos aplicamos 250 µg de Cu-His, sin efectos indeseables relevantes durante 30 días y observamos las siguientes determinaciones séricas de cobre (Cu en µg/L) y ceruloplasmina (Cp en mg/dL): caso 1, Cu días 0 y 30, 8 y 504 µg/L; Cp días 0 y 30, 4 y 10.75 mg/dL; caso 2, Cu días 0 y 30, < 50 y 502, µg/L; Cp días 0 y 30, 2 y 15 mg/dL; caso 3, Cu días 0 y 30, 3 y 84.2 µg/L; Cp días 0 y 30, 4 y 10.7 mg/dL. En México es posible la síntesis segura de Cu-His y tratar la enfermedad de Menkes, la cual debe ser intencionalmente buscada.

Abstract Menkes disease is a neurodegenerative and lethal pathology caused by gene mutations of the copper-transporting ATP-7A enzyme; it manifests itself by neurological symptoms and connective tissue changes of varying severity. Timely subcutaneous use of copper histidinate (Cu-His) is determinant for quality of life. We report the first experiences in Mexico on Cu-His synthesis and its safe use in 3 cases where hypocupremia and hypoceruloplasminemia were corroborated. With advice of the Hospital for Sick Children of Toronto Canada, we prepared a 500 µg/mL solution. In all three cases were 250 µg of Cu-His applied without relevant undesirable effects for 30 days. Serum copper (Cu, expressed in µg/L) and ceruloplasmin (Cp, in mg/dL) were determined: case 1, Cu days 0 and 30, 8 and 504 µg/L; Cp days 0 and 30, 4 and 10.75 mg/dL; case 2, Cu days 0 and 30, <50 and 502 µg/L; Cp days 0 and 30, 2 and 15 mg/dL; case 3, Cu days 0 and 30, 3 and 84.2 µg/L; Cp days 0 and 30, 4 and 10.7 mg/dL. In Mexico, it is possible to safely synthesize Cu-His and treat MD, which must be intentionally sought.

The maturation state of the auditory nerve and brainstem in rats exposed to lead acetate and supplemented with ferrous sulfate / Estado de maturação do nervo auditivo e tronco encefálico em ratos expostos a acetato de chumbo e suplementados com sulfato ferroso

Abstract Introduction The literature has reported the association between lead and auditory effects, based on clinical and experimental studies. However, there is no consensus regarding the effects of lead in the auditory system, or its correlation with the concentration of the metal in the blood. Objective To investigate the maturation state of the auditory system, specifically the auditory nerve and brainstem, in rats exposed to lead acetate and supplemented with ferrous sulfate. Methods 30 weanling male rats (Rattus norvegicus, Wistar) were distributed into six groups of five animals each and exposed to one of two concentrations of lead acetate (100 or 400 mg/L) and supplemented with ferrous sulfate (20 mg/kg). The maturation state of the auditory nerve and brainstem was analyzed using Brainstem Auditory Evoked Potential before and after lead exposure. The concentration of lead in blood and brainstem was analyzed using Inductively Coupled Plasma-Mass Spectrometry. Results We verified that the concentration of Pb in blood and in brainstem presented a high correlation (r = 0.951; p < 0.0001). Both concentrations of lead acetate affected the maturation state of the auditory system, being the maturation slower in the regions corresponding to portion of the auditory nerve (wave I) and cochlear nuclei (wave II). The ferrous sulfate supplementation reduced significantly the concentration of lead in blood and brainstem for the group exposed to the lowest concentration of lead (100 mg/L), but not for the group exposed to the higher concentration (400 mg/L). Conclusion This study indicate that the lead acetate can have deleterious effects on the maturation of the auditory nerve and brainstem (cochlear nucleus region), as detected by the Brainstem Auditory Evoked Potentials, and the ferrous sulphate can partially amend this effect.

Resumo Introdução A literatura relatou a associação entre o chumbo e os efeitos auditivos, com base em estudos clínicos e experimentais. No entanto, não há consenso em relação aos efeitos do chumbo no sistema auditivo, ou sua correlação com a concentração do metal no sangue. Objetivo Investigar o estado de maturação do sistema auditivo, especificamente do nervo auditivo e do tronco encefálico, em ratos expostos ao acetato de chumbo e suplementados com sulfato ferroso. Método 30 ratos machos desmamados (Rattus norvegicus, Wistar) foram distribuídos em seis grupos de cinco animais e expostos a uma de duas concentrações de acetato de chumbo (100 ou 400 mg/L) e suplementados com sulfato ferroso (20 mg/kg). O estado de maturação do nervo auditivo e do tronco encefálico foi analisado pelo Potencial Evocado Auditivo do Tronco Encefálico antes e após a exposição ao chumbo. A concentração de chumbo no sangue e tronco encefálico foi analisada utilizando-se Espectrometria de Massa com Plasma Indutivamente Acoplado. Resultados Verificamos que as concentrações de Pb no sangue e no tronco encefálico apresentaram alta correlação (r = 0,951, p < 0,0001). Ambas as concentrações de acetato de chumbo afetaram o estado de maturação do sistema auditivo, a maturação foi mais lenta nas regiões correspondentes à porção do nervo auditivo (onda I) e dos núcleos cocleares (onda II). A suplementação com sulfato ferroso reduziu significativamente a concentração de chumbo no sangue e no tronco encefálico no grupo exposto à menor concentração de chumbo (100 mg/L), mas não para o grupo exposto à maior concentração (400 mg/L). Conclusão Esse estudo indica que o acetato de chumbo pode ter efeitos deletérios na maturação do nervo auditivo e do tronco encefálico (região do núcleo coclear), como detectado pelos potenciais evocados auditivos do tronco encefálico, e que o sulfato ferroso pode diminuir parcialmente esse efeito.

Efficacy and safety of amphotericin B deoxycholate versus N-methylglucamine antimoniate in pediatric visceral leishmaniasis: an open-label, randomized, and controlled pilot trial in Brazil

ABSTRACT INTRODUCTION Despite their high toxicity, antimonials and amphotericin B deoxycholate are commonly used for treating visceral leishmaniasis (VL). Few studies showing conflictive data about their efficacy and adverse events in pediatric population are available. This study aimed to evaluate efficacy and safety of amphotericin B deoxycholate vs. that of N-methylglucamine antimoniate in treating pediatric VL in Brazil. METHODS This was a randomized, open-label, 2-arm and controlled pilot clinical trial. Treatment naïve children and adolescents with VL without signs of severe illness were treated with N-methylglucamine antimoniate (20mg/kg/day for 20 days) or amphotericin B deoxycholate (1 mg/kg/day for 14 days). All patients were diagnosed with positive direct examination and/or positive PCR for Leishmania spp. performed in bone marrow samples. The primary efficacy end-point was VL cure determined after 180 days of completion of treatment. The analysis was performed using intention-to-treat (ITT) and per protocol (PP) analyses. RESULTS In total, 101 volunteers were assessed. Efficacy was similar for both groups. The antimonial (n=51) and amphotericin B groups (n=50) had a cure rate of 94.1% and 100%, and 94% and 97.9% according to ITT and PP analyses, respectively. All patients reported adverse events (AE). Serious AE incidence was similar in both groups. Five individuals were excluded from the study because of severe adverse events. CONCLUSIONS N-methylglucamine antimoniate and amphotericin B deoxycholate have similar efficacy and adverse events rate in pediatric patients with VL.

Wheat sprout effects on histological and histometrical structure and sperm parameters in testis of rat exposed to lead

Background: Wheat sprout contains a high amount of antioxidants, vitamins [especially vitamin E], minerals and phytoestrogen compounds. Use of medicinal herbs in reducing heavy metal toxicities has increased worldwide. In recent years, negative effects of lead on the male reproductive system and sperm fertility parameters have been shown broadly

Objectives: This study investigated the effects of wheat sprout extract [WSE] and vitamin E on sperm parameters and testicular oxidative stress in rats exposed to lead acetate

Methods: Thirty-five rats were divided randomly into seven groups: Gl [control group] received 1 ml/kg/day of normal saline, G2 received 20 mg/kg/day of lead acetate, G3 and G4 received 100 mg/kg/day and 200 mg/kg/day of WSE respectively, G5 and G6 received 100 mg/kg/day and 200 mg/kg/day of WSE respectively with 20 mg/kg/day of lead acetate, and G7 received 100 mg/kg/day of vitamin E with 20 mg/kg/day of lead acetate. After 35 days, rats were sacrificed and blood, sperm, liver and testicle tissue samples were collected for histomorphological and histochemical studies

Results: Results showed that count, motility and viability of sperms increased following the administration of 200 mg/kg/day of WSE [p<0.01]. Histomorphological studies showed a significant increase in tubular differentiation index [TDI], Repopulation index [RI], number of Sertoli cells, and epithelium of seminiferous tubules in groups receiving 200 mg/kg/day of WSE [p<0.00l]

Conclusions: Results of the current study show that dose dependent WSE significantly prevents testicular toxicity and oxidative stress effects of lead acetate

Estudio comparativo entre el uso de manitol y el picosulfato sódico como preparación para colonoscopía / Comparison of colon-cleansing methods in preparation for colonoscopy- comparative of solutions of mannitol and sodium picosulfate

Objetivos: El objetivo del presente estudio es comparar la preparación adecuada del colon con manitol y picosulfato sódico. Evaluar la aceptación de los pacientes, los efectos secundarios y la capacidad de limpieza. Materiales y métodos: Este es un estudio no aleatorio, prospectivo, ciego, en que el evaluador no tenía información sobre la preparación aplicada. La muestra obtenida se dividió en dos grupos de acuerdo con la preparación adecuada del colon, con 153 pacientes preparados con manitol al 10% y 84 pacientes con picosulfato sódico. La evaluación de la preparación se realizó usando la Escala de Boston (Boston Bowel Preparation Scale - BBP) a través de un sistema de puntuación para cada región del colon puntuada con 3 puntos: derecha, izquierda y colon transverso. Resultados: De los 237 pacientes que fueron evaluados, 146 (61,60%) eran mujeres y 91 (38,4%) eran hombres. En el grupo que utilizó manitol, 98 (64,05%) eran mujeres y 55 (35,95%) eran varones. Entre los pacientes que utilizaron picosulfato sódico, 48 (57,14%)eran mujeres y 36 (42,86%) eran hombres, sin diferencias estadísticas de ambos grupos (p>0,32). Teniendo en cuenta que con la adecuada preparación del colon y con puntuación de 6 puntos en la Escala de Boston, la preparación intestinal fue satisfactoria en ambos grupos. El 93% de los pacientes que utilizaron manitol y el 81% de los pacientes que utilizaron picosulfato sódico tenían preparación adecuada (puntuación de 6). La puntuación media en la preparación con manitol fue de 9 y en la preparación con picosulfato sódico fue de 7. No hubo diferencias significativas entre ambos grupos. Conclusión: Ambas preparaciones, demostraron ser seguras y eficaces para la limpieza del intestino, de acuerdo con la Escala de Boston, así como, la aceptabilidad de los pacientes y libre de complicaciones

Objectives: The purpose of the present study is to compare intestinal preparation with mannitol and sodium picosulphate, assessing patient’s acceptance, side effects and cleaning capacity. Material and methods: This is a prospective, nom randomized, blind study, in which the evaluator had no information about the preparation applied. The sample obtained was divided into two groups according to the bowel preparation applied, with 153 patients prepared with 10% mannitol and 84 patients with sodium picosulfate. The evaluation of colon preparation was done using the Boston Scale (Boston Bowel Preparation Scale - BBP) through a three-point scoring system for each of the three regions of the colon: right, left and transverse colon. Results: Of the 237 patients that were evaluated, 146 (61.60%) were female and 91 (38.4%) were male. Regarding the group that used mannitol, 98 were female (64.05%) and 55 were male (35.95%). Among the patients who used sodium picosulfate, 48 were female (57.14%) and 36 were male (42.86%), with no statistical differences between both groups (p> 0.32). Considering that an adequate preparation scores ≥ 6 in the Boston Scale, the bowel cleansing preparation was satisfactory in both groups. 93% of the patients who used mannitol and 81% of the patients who used sodium picosulfate had adequate preparation (score of ≥ 6). Moreover, we consider that the average score in the preparation with Mannitol was 9, while the sodium picosulfate score was 7. There were no significant differences between the two groups. Conclusion: There is consensus among authors who state that colonoscopy’s safety and success are highly related to the cleansing outcome, regardless of the method used. The same can be observed in the present study, on which both preparations were proved safe and effective for bowel cleansing, according to the Boston scale, as well as accepted by patients and free of complications

Intralesional meglumine antimoniate for the treatment of localised cutaneous leishmaniasis: a retrospective review of a Brazilian referral centre

Although intralesional meglumine antimoniate (MA) infiltration is considered an option for cutaneous leishmaniasis (CL) therapy and is widely used in the Old World, there have been few studies supporting this therapeutic approach in the Americas. This study aims to describe outcomes and adverse events associated with intralesional therapy for CL. This retrospective study reviewed the experience of a Brazilian leishmaniasis reference centre using intralesional MA to treat 31 patients over five years (2008 and 2013). The median age was 63 years (22-86) and the median duration time of the lesions up to treatment was 16 weeks. In 22 patients (71%), intralesional therapy was indicated due to the presence of contraindications or previous serious adverse events with systemic MA. Other indications were failure of systemic therapy or ease of administration. Intralesional treatment consisted of one-six infiltrations (median three) for a period of up to 12 weeks. The initial (three months) and definitive (six months) cure rates were 70.9% and 67.7%, respectively. Most patients reported mild discomfort during infiltration and no serious adverse events were observed. In conclusion, these results show that the intralesional MA efficacy rate was very similar to that of systemic MA treatment, and reinforce the need for further studies with adequate design to establish the efficacy and safety of this therapeutic approach.

Historical seriss of patients with visceral leihmaniasis treated with megluminne antimoniate in a hospital for tropical diseases, Maceió-AL, Brazil / Série histórica dos pacientes com leishmaniose visceral tratados com antimoniato de meglumina em hospital de Doenças Tropicais, Maceió-AL, Brasil

Introduction: Visceral leishmaniasis is an endemic protozoan found in Brazil. It is characterized by fever, pallor, hepatosplenomegaly, lymphadenopathy, and progressive weakness in the patient. It may lead to death if untreated. The drug of choice for treatment is meglumine antimoniate (Glucantime®). The aim of this study was to evaluate patients with visceral leishmaniasis according to criteria used for diagnosis, possible reactions to Glucantime® and blood pressure measured before and after treatment. Methods: 89 patients admitted to the Teaching Hospital Dr. Hélvio Auto (HEHA) in Maceió-AL, in the period from May 2006 to December 2009 were evaluated. Data were collected on age, sex, origin, method of diagnosis, adverse effects of drugs, duration of hospitalization, duration of treatment and dosage up to the onset of adverse effects. Results: There was a predominance of child male patients, aged between one and five years old, from the interior of the State of Alagoas. Parasitological diagnosis was made by bone marrow aspirate; three (3.37%) patients died, 12 (13.48%) had adverse reactions and treatment was changed to amphotericin B, and 74 (83.14%) were cured. Changes that led to replacing Glucantime® were persistent fever, jaundice, rash, bleeding and cyanosis. Conclusion: During the study, 89 patients hospitalized for VL were analyzed: 74 were healed, 12 were replaced by amphotericin B treatment and three died. Most of them were under five years old, male and came from the interior. The dosage and duration of treatment with Glucantime® were consistent with that advocated by the Ministry of Health. Persistence of fever, jaundice, rash, cyanosis and bleeding were the reactions that led the physician to modify treatment. No change was observed in blood pressure before and after treatment. This study demonstrated the work of a hospital, a reference in the treatment of leishmaniasis, which has many patients demanding its services in this area. It demonstrates that this disease is still important today, and needs to be addressed properly to prevent injury and death due to the disease.

A Leishmaniose visceral é doença infecciosa causada por protozoários das espécies chagasi e donovani sendo transmitida pela picada de insetos fêmea dos gêneros Lutzomyia e Phlebotomos. Constitui doença febril, determinando amplo aspecto de manifestações clínicas e prognóstico variável, que pode levar à morte se não for tratada. É doença endêmica encontrada no Brasil e nos últimos anos verificou-se intenso processo de urbanização da endemia e aumento da letalidade por leishmaniose visceral. O estudo teve como objetivo avaliar pacientes com leishmaniose visceral de acordo com os critérios utilizados para o diagnóstico, possíveis reações ao Glucantime® e pressão arterial, medidos antes e após o tratamento. Métodos: Foram avaliados 89 pacientes internados no Hospital Universitário Dr. Hélvio Auto (HEHA), em Maceió-AL, no período de maio de 2006 a dezembro de 2009. Foram coletados dados sobre idade, sexo, origem, método de diagnóstico, efeitos adversos da droga, duração da hospitalização, duração do tratamento e dose até o aparecimento de efeitos adversos. Resultados: Houve predomínio de crianças do sexo masculino, com idade entre um e cinco anos, a partir do interior do Estado de Alagoas. O diagnóstico parasitológico foi feito pelo aspirado de medula óssea, três (3,37%) pacientes morreram, 12 (13,48 %) apresentaram reações adversas e o tratamento foi alterado para anfotericina B, e 74 (83,14 %) foram curados. As alterações que levaram à substituição de Glucantime® foi febre persistente. A dosagem e duração do tratamento com Glucantime® foi seguido como preconizado pelo Ministério da Saúde. A persistência de febre, icterícia, prurido, cianose e sangramento foram as reações que levaram o médico a modificar o tratamento. Nenhuma mudança foi observada na pressão arterial antes e após o tratamento. O estudo realizado demonstrou o perfil de um Hospital, que recebe grande demanda de casos de leishmaniose visceral. Isso demonstra que essa doença continua sendo importante na atualidade, precisando ser abordada de maneira adequada, evitando assim agravos e mortes pela doença.

Efficacy and safety of glucantime for cutaneous leishmaniasis - eight years experience at a tertiary care hospital of Karachi

To observe the efficacy and adverse effect profile of Glucantime in treatment of cutanous leishmaniasis. Cross sectional study. This study was conducted in Dermatology Department, JPMC Karachi from Jan 2007 to Jan 2015. 252 patients of CL, diagnosed clinically and confirmed parasitologically were treated with injection glucantime. After taking history and physical examination, baseline complete blood count ,Liver function tests, Renal function tests and ECG were performed. 76 patients were treated with intralesional injection and 156 patients were treated with intramuscular Glucantime. Treatment response was observed and adverse effects were noted. The data was recorded and analysed on SPSS version 16. Mean +/- SD was calculated for continuous variables like age, duration of disease. Categorical values like gender, type, morphology, site of lesions efficacy and adverse effects were recorded as numbers and percentages. The mean age of I/L group was 31.4 +/- 11.6 and for I/M group. Efficacy of Intramuscular Glucantime was76.3% in intralesional group and 86.9%in intramuscular group. Adverse effects were seen in 25 % of intralesional and 26.9 % of intramuscular group. Glucantime is effective and well tolerated drug in Old world CL both by intramuscular or intralesional route

Acute Respiratory Distress Syndrome after the Use of Gadolinium Contrast Media

Acute respiratory distress syndrome (ARDS) is a medical emergency that threatens life. To this day, ARDS is very rarely reported by iodine contrast media, and there is no reported case of ARDS induced by gadolinium contrast media. Here, we present a case with ARDS after the use of gadobutrol (Gadovist) as a magnetic resonance imaging (MRI) contrast medium. A 26 years old female without any medical history, including allergic diseases and without current use of drugs, visited the emergency room for abdominal pain. Her abdominopelvic computed tomography with iodine contrast media showed a right ovarian cyst and possible infective colitis. Eighty-three hours later, she underwent pelvis MRI after injection of 7.5 mL (0.1 mL/kg body weight) of gadobutrol (Gadovist) to evaluate the ovarian cyst. She soon presented respiratory difficulty, edema of the lips, nausea, and vomiting, and we could hear wheezing upon auscultation. She was treated with dexamethasone, epinephrine, and norepinephrine. Her chest X-ray showed bilateral central bat-wing consolidative appearance. Managed with mechanical ventilation, she was extubated 3 days later and discharged without complications.

First report onoototoxicity of meglumine antimoniate / Primeiro relato de ototoxicidade pelo antimoniato de meglumina

Introduction: Pentavalent antimonials are the first drug of choice in the treatment of tegumentary leishmaniasis. Data on ototoxicity related with such drugs is scarcely available in literature, leading us to develop a study on cochleovestibular functions. Case Report: A case of a tegumentary leishmaniasis patient, a 78-year-old man who presented a substantial increase in auditory threshold with tinnitus and severe rotatory dizziness during the treatment with meglumine antimoniate, is reported. These symptoms worsened in two weeks after treatment was interrupted. Conclusion: Dizziness and tinnitus had already been related to meglumine antimoniate. However, this is the first well documented case of cochlear-vestibular toxicity related to meglumine antimoniate.

Introdução: Antimoniais pentavalentes são os fármacos de primeira escolha no tratamento da leishmaniose tegumentar. Dados de ototoxicidade relacionados a tais fármacos são escassos na literatura, o que nos levou a desenvolver um estudo de funções cócleo-vestibulares. Relato de caso: Relatamos caso de paciente masculino de 78 anos com leishmaniose tegumentar, que apresentou aumento significativo dos limiares auditivos com zumbido e tontura rotatória grave durante o tratamento com antimoniato de meglumina. Os sintomas pioraram até duas semanas após a interrupção do tratamento. Conclusão: Tontura e zumbido já tinham sido associados ao antimoniato de meglumina. Entretanto, este é o primeiro caso bem documentado de toxicidade cócleo-vestibular relacionado ao antimoniato de meglumina.

Montenegro skinttest and age of skin lesion as redictors of treatment failure in cutaneous leishmaniasis / Intensidade da intradermorreação de Montenegro e tempo de evolução da lesão como preditores de falha na resposta terapêutica da leishmaniose cutânea

A case-control study was conducted to examine the association among the Montenegro skin test (MST), age of skin lesion and therapeutic response in patients with cutaneous leishmaniasis (CL) treated at Evandro Chagas National Institute of Infectious Diseases (INI), Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, Brazil. For each treatment failure (case), two controls showing skin lesion healing following treatment, paired by sex and age, were randomly selected. All patients were treated with 5 mg Sb5+/kg/day of intramuscular meglumine antimoniate (Sb5+) for 30 successive days. Patients with CL were approximately five times more likely to fail when lesions were less than two months old at the first appointment. Patients with treatment failure showed less intense MST reactions than patients progressing to clinical cure. For each 10 mm of increase in MST response, there was a 26% reduction in the chance of treatment failure. An early treatment - defined as a treatment applied for skin lesions, which starts when they are less than two months old at the first appointment -, as well as a poor cellular immune response, reflected by lower reactivity in MST, were associated with treatment failure in cutaneous leishmaniasis.

Conduzimos estudo caso-controle que verificou a associação entre a intradermorreação de Montenegro (IDRM), o tempo de evolução da lesão e a resposta terapêutica em pacientes com leishmaniose cutânea (LC) atendidos no Instituto de Infectologia Evandro Chagas (INI), Fundação Oswaldo Cruz (Fiocruz), Rio de Janeiro, Brasil. Para cada caso com má resposta à terapêutica foram selecionados aleatoriamente dois controles que evoluíram com cicatrização das lesões após o tratamento, pareados por sexo e idade. Todos os pacientes realizaram tratamento com antimoniato de meglumina (Sb5+) IM, na dose de 5 mg Sb5+/kg/dia, continuamente, por 30 dias. Pacientes com LC apresentaram aproximadamente cinco vezes mais chance de falhar quando as lesões apresentavam menos de dois meses de evolução no primeiro dia de atendimento. Pacientes com falha terapêutica apresentaram reações de IDRM menos intensas que pacientes que evoluíram para a cura clínica. A cada 10 milímetros de aumento na resposta à IDRM, houve uma redução de 26% na chance de ocorrência de falha. O tratamento precoce, traduzido pelo tempo de evolução da lesão menor que dois meses no primeiro dia de atendimento, e resposta de imunidade celular deficiente, traduzida por IDRM menos intensa, demonstraram contribuir para a ocorrência de falha terapêutica na leishmaniose cutânea.

Resolution of cttaneous leishmaniasis after acue eczema due to intralesional mmeglumine antimoniate / Resolução de leishmaniose cutânea após eczema agudo devido a antimoniato de meglumina intralesional

We report a case of a 42 year-old female, who came to a leishmaniasis reference center in Rio de Janeiro, Brazil, presenting a cutaneous leishmaniasis lesion in the right forearm. Treatment with low-dose intramuscular meglumine antimoniate (MA) (5 mg Sb5+/kg/day) was initiated, with improvement after 28 days, although with the development of generalized eczema. After 87 days, the lesion worsened. Patient refused treatment with amphotericin B. MA was then infiltrated in the lesion, in two sessions, resulting in local eczema, with bullae formation; however, twenty days after, both the ulcer and eczema receded. Intralesional administration of MA should be used carefully when previous cutaneous hypersensitivity is detected.

Relatamos caso de paciente de 42 anos atendida em centro de referência em leishmanioses no Rio de Janeiro, Brasil, apresentando lesão de leishmaniose cutânea no antebraço direito. Iniciado tratamento com baixa dose de antimoniato de meglumina (AM) intramuscular (5 mg Sb5+/kg/dia), houve melhora após 28 dias, porém com desenvolvimento de eczema generalizado. Após 87 dias, notou-se piora da lesão. A paciente recusou o tratamento com anfotericina B. Infiltrou-se AM na lesão em duas sessões, resultando em eczema local com bolhas. Entretanto, 20 dias depois, tanto a úlcera quanto o eczema regrediram. A administração intralesional do AM deve ser utilizada com cautela em pacientes com hipersensibilidade cutânea a este fármaco.

[Side effects of meglumine antimoniate in cutaneous leishmaniasis: 15 cases]

Leishmaniasis is wide spread parasitic disease considered to be endemic in 88 countries in both old and new world. The standard treatment remains Meglumine antimoniate. We study the side effects of systemic meglumine antimoniate in cutaneous leishmaniasis. We conduct a retrospective study covering 3-year period [2002- 2005]. All medical reports of cutaneous leishmaniasis treated by systemic Meglumine antimoniate are reviewed. The study comprise 63 patients all treated by systemic meglumine antimoniate at the dose of 60mg/kg/day for 10-15 days. Side effects were noted in 15 cases [12 females and 3 males] .The subject's age range from 11 to 78 years. Stibio-intolerance [fever, rash, arthralgia, abdominal pain] was observed in 12 cases and stibio-toxicity in 3 cases: precordialgies 1 case, hyperamylasemia and increase liver enzyme: 1 case, pancytopenia, renal and hepatic failure leading to death: 1 case, skin eruption: 7 cases, pruritis and erythema in the site of injection: 5 cases, urticaria: 1 case. Meglumine antimoniate was stopped in 13 cases Meglumine antimoniate is the generally recommended treatment of cutaneous leishmaniasis. In spite of the rarity of Glucantime's side effects, we recommend a careful survey especially in older patients

Failure of both azithromycin and antimony to treat cutaneous leishmaniasis in Manaus, AM, Brazil / Falha da azitromicina e do antimonial no tratamento da leishmaniose cutânea em Manaus, AM, Brasil

A non-randomized controlled clinical trial was carried outin order to evaluate both azithromycin and antimony efficacy in cutaneous leishmaniasis in Manaus, AM, Brazil. Forty nine patients from both genders, aged 14 to 70, with cutaneous ulcers for less than three months and a positive imprint for Leishmania spp. amastigotes were recruited into two groups. Group I (26 patients) received a daily-single oral dose of 500 mg of azithromycin for 20 days and Group II (23 patients) received a daily-single intramuscular dose of 20 mg/kg of meglumine antimony, also for 20 days. Azithromycin cured three of 24 (12.5 percent) patients on days 60, 90 and 120 respectively whereas therapeutic failure was considered in 21 of 24 (87.5 percent) cases. In group II, antimony cured eight of 19 (42.1 percent) cases as follows: three on day 30, one each on day 60 and day 90, and three on day 120. Therapeutic failure occurred in 11 of 19 (57.9 percent) individuals. The efficacy of antimony for leishmaniasis was better than azithromycin but analysis for the intention-to-treat response rate did not show statistical difference between them. Although azithromycin was better tolerated, it showed a very low efficacy to treat cutaneous leishmaniasis in Manaus.

Com o objetivo de avaliar a eficácia da azitromicina no tratamento da leishmaniose cutânea, foi realizado ensaio comparativo, em Manaus. Foram recrutados 49 pacientes de ambos os sexos, com idades entre 14 e 70 anos que apresentassem úlceras cutâneas com menos de três meses de evolução e que tivessem exame direto positivo para amastigotas de leishmânia. Estes pacientes foram alocados em dois grupos assim: Grupo I (26) recebeu uma dose diária de 500 mg de azitromicina pela via oral durante 20 dias e o Grupo II, recebeu uma dose diária de 20 mg/kg de antimoniato de meglumina por via intramuscular, durante 20 dias. Do grupo da azitromicina, três (12,5 por cento) de 24 pacientes curaram 60, 90 e 120 dias, respectivamente, enquanto, em 21 (87,5 por cento) de 24 houve falha terapêutica. No grupo do antimonial, oito (42,5 por cento) de 19 pacientes curaram como segue: três no dia 30, um no dia 60, um no dia 90 e três no dia 120. Contudo, em 11 (57,9 por cento) de 19 casos, houve falha terapêutica. A azitromicina foi menos eficaz do que o antimonial, embora, a análise da taxa de resposta por intenção de tratamento não mostrou diferença significativa, entre eles. A azitromicina foi melhor tolerada; porém, mostrou-se pouco eficaz no tratamento da leishmaniose cutânea, em Manaus.

[Evaluation of lead acetate side effects on rat hippocampus and the effects of vitamin C on these]

To investigate the effect of ascorbic acid against lead-induced neurotoxicity in the rat hippocampus. The heads of 40 male Sprague-Dawley rats were divided into 4 groups: normal, control, lead-treated and lead plus ascorbic acid-treated. Lead acetate [20mg/kg] was administered intraperitonealy to rats for 7days in third and fourth groups. During this period, rats in the fourth group received 500 mg ascorbic acid, in drinking water daily. At the end of the treatment, all rats were sacrified and their hippocamps were excluded. Using TEM the samples were examined in terms of natural and apoptotic cells. Histopathological evaluation showed that apoptosis was attenuated significantly in the ascorbic acid group but not in the lead group. Simultaneous administration of ascorbic acid and lead increased the level of Bcl-2 and decreased Bax protein compared with lead-treated only. It seems that ascorbic acid may reduce the lead-induced toxicity in central nervous system

An alternative antimonial schedule to be used in cutaneous leishmaniasis when high doses of antimony are undesirable

Despite more than half a century of use in leishmaniasis, antimony therapy still presents serious problems concerning dosage and toxicity. Low and high doses have been shown to be equally effective. In this paper, the feasibility of injecting one ampoule of meglumine antimoniate intramuscularly every other day until clinical cure is demonstrated, while studying a series of 40 cutaneous leishmaniasis cases. Total dose used varied from 1,822.5 to 12,150mg of pentavalent antimony and total time of treatment varied from 3 to 10 weeks, with 86 percent efficacy. Thirty-six out of the 40 patients are still on follow-up with a mean time of 10.7 ± 7 months and a median of 9 months. No relapse or mucosal lesions have been noted so far. The schedule showed good tolerance and easy application and its efficacy was comparable to the officially recommended WHO schedule. Therefore, such a schedule represents a valuable alternative for the cases with high toxicicity to antimony or daily injections are an obstacle to the treatment.

Apesar de utilizado há mais de meio século no tratamento da leishmaniose, o antimônio apresenta ainda problemas quanto a sua toxicidade e dose ideal. Doses baixas têm se mostrado tão eficazes quanto doses altas. Neste trabalho, apresentamos o resultado do emprego de uma ampola de antimoniato de meglumina intramuscular, em dias alternados, até a cura clínica, numa série de 40 casos. A dose total utilizada, por paciente, variou de 1.822,5 a 12.150mg de antimônio pentavalente e o tempo de tratamento de 3 a 10 semanas com eficácia de 86 por cento. Dos 40 pacientes estudados, 36 ainda estão em acompanhamento, com um tempo médio de 10,7 ± 7 meses e média de 9 meses. Não houve recidivas nem lesões mucosas. O esquema utilizado foi bem tolerado, de fácil aplicação, eficácia comparável ao esquema oficialmente preconizado pela OMS, mostrando-se como valiosa alternativa para os casos com potencial toxicidade ao antimônio ou cuja aplicação de injeções diárias represente um obstáculo ao tratamento.

Treatment of bone pain secondary to metastases using samarium-153-EDTMP

CONTEXTO: Mais de 50% dos pacientes com câncer de próstata, mama ou pulmão desenvolverão dor óssea secundária a metástases. O tratamento da dor óssea metastática visa minimizar a dor, reduzir o uso de opióides e manter os movimentos. OBJETIVO: Avaliar o uso de EDTMP-153Sm para tratamento da dor óssea secundária a metástases refratária a tratamento com opióides. TIPO DE ESTUDO: Retrospectivo. LOCAL: Divisão de Medicina Nuclear, Universidade Estadual de Campinas (Unicamp). MÉTODOS: 58 pacientes foram estudados (34 homens), com média de idade de 62 anos. 31 pacientes com neoplasia de próstata, 20 com neoplasia de mama, três pacientes com câncer de pulmão, um com hemangioendotelioma de pulmão, um com adenocarcinoma de paratireóide, um com osteosarcoma e um paciente que apresentava um tumor primário desconhecido. Todos apresentavam múltiplas metástases ósseas à cintilografia óssea com MDP-99mTc e foram tratados com EDTMP-153Sm. A resposta ao tratamento foi graduada em boa (redução da dor em 50 - 100%), intermediária (25-49%) e má (0-24%). RESULTADOS: Todos os pacientes apresentavam boa captação de EDTMP-153Sm nas metástases ósseas. Dentre os doentes com câncer de próstata, resposta intermediária ou boa ocorreu em 80.6% (25 pacientes) e má resposta em 19.4% (6). Dentre os pacientes com câncer de mama, 85% (17) apresentaram resposta intermediária ou boa à terapia enquanto 15% (3) apresentaram má resposta. Todos os três pacientes com câncer de pulmão apresentaram resposta pobre ao tratamento. Os doentes com hemangioendotelioma de pulmão e com o tumor primário desconhecido apresentaram resposta intermediária ao tratamento; os pacientes com osteossarcoma e com o adenocarcinoma de paratireóide apresentaram boa resposta. Mielotoxicidade significativa não ocorreu. DISCUSSAO: O controle da dor é importante para melhorar a qualidade de vida do doente com câncer avançado. O mecanismo de alívio da dor com radionuclídeos ainda não foi elucidado, mas o tratamento é de simples administração e baixo risco de mielotoxidade. CONCLUSAO: Tratamento com EDTMP-153Sm pode controlar a dor secundária a metástases ósseas de forma efetiva na maioria dos pacientes com câncer de próstata e câncer de mama sem efeitos colaterais significativos.

Retrospective evaluation of bone pain palliation after samarium-153-EDTMP therapy

OBJETIVO: O presente trabalho teve por objetivo avaliar o efeito paliativo da dor e a toxicidade medular associados ao tratamento com Samário-153-EDTMP em pacientes com metástases ósseas. MÉTODOS: O estudo foi realizado de forma retrospectiva, a partir do levantamento de prontuário de 178 pacientes submetidos a tratamento com 1mCi/kg de 153Sm-EDTMP devido à dor por metástases ósseas. Os prontuários de 73 pacientes foram considerados adequados para análise dos parâmetros clínicos (intensidade da dor) e laboratoriais (hemograma). A intensidade da dor foi avaliada em escala de 0 a 10 pelo próprio paciente, antes e durante 8 semanas após o tratamento. Hemograma completo foi realizado antes do tratamento e a cada semana nas 8 semanas seguintes. Estudos de dosimetria foram realizados em 41 dos 73 pacientes, baseados na excreção urinária e retenção do radioisótopo, sendo a dose de radiação absorvida correlacionada à toxicidade medular. RESULTADOS: Redução importante na intensidade da dor (diminuição de 75 a 100% do basal) foi constatada em 36 pacientes (49%), com redução de 50-75%, 25-50% e 0-25% em, respectivamente, 20 (27%), 10 (14%) e 7 (10%) casos. Não se observou variação significativa da resposta entre os pacientes com tumor primário de mama (n=29) ou de próstata (n=36). Toxicidade medular foi observada em 75,3% dos pacientes (71,2% com leucopenia e 53,4% com plaquetopenia), em geral de grau leve a moderado e com recuperação ao término da 8º semana. A dose média de medula foi de 347±65 cGy, havendo baixa correlação entre a dosimetria medular e a queda da contagem de leucócitos (coeficiente de correlação linear de 0,40) ou de plaquetas (coeficiente de correlação linear = 0,48). CONCLUSÕES: O tratamento com Samário-153-EDTMP permitiu um adequado controle da dor por metástases ósseas, com significativa redução na intensidade da dor. A toxicidade medular transitória foi a principal reação adversa observada, em geral de grau leve a moderado, apresentando baixa correlação com as medidas dosimétricas.

Avaliação da tolerância e nefrotoxicidade do antimonial pentavalente administrado na dose de 40 mg Sb V/kg/dia, de 12/12 h, por 30 dias na forma cutâneo-mucosa de leishmaniose / The evaluation of the tolerance and nephrotoxicity of pentavalent antimony administered in a dose of 40 mg Sb V/kg/day, 12/12 hr, for 30 days in the mucocutaneous form of leishmaniasis

Foi avaliada a função renal de 11 pacientes com leishmaniose cutâneo-mucosa tratados com antimonial pentavalente na dose de 40mg SbV/kg/dia aplicada de 12/12 horas, em esquema contínuo, durante trinta dias. No estudo, um paciente apresentou insuficiência renal reversível e dois desenvolveram alterações enzimáticas hepáticas e eletrocardiográficas sendo o esquema terapêutico interrompido. Nos demais pacientes observou-se efeitos nefrotóxicos tais como diminuição da taxa de filtração glomerular, diminuição da capacidade de concentração urinária, avaliada por um jejum hídrico de 16 horas e aumento na fração de excreção de sódio. No exame do sedimento urinário observou-se um aumento no número de leucócitos e cilindros. Os resultados encontrados neste estudo sugerem que o tratamento com antimonial pentavalente na dose de 40mg SbV/kg/dia foi menos tolerado em virtude de seus efeitos tóxicos, não parecendo apresentar índice de cura superior ao esquema atualmente preconizado de 20mg SbV/kg/dia.

The renal function of eleven patients with mucocutaneous leishmaniasis was analyzed in a prospective study realized at the School Hospital of University of Brasília. The patients were treated with doses of 40 mg/kg/day of pentavalent antimony (Sb V), in a continuous scheme during thirty days. In this study three patients were excluded, one patient with reversible renal failure and two patients with hepatic and cardiac malfunctions. In the other eight patients, severe nephrotoxic effects were observed, like reduction of glomerular filtration rate, reduction of the urinary concentration capacity, evaluated by a sixteen hours hydric fasting and an increase of sodium fractional excretion. An increase in the number of leucocytes and cylinders were observed at the urinary sediment exam. Finally, the results shows that the treatment with pentavalent antimony in doses of 40 mg Sb/kg/day was less tolerated on account of its renal toxic effects. This scheme seems not be superior than the currently preconized scheme of 20 mg of Sb V/kg/day during 30 days.