Efficacy of topical clotrimazole vs. topical tolnaftate in the treatment of otomycosis. A randomized controlled clinical trial / Eficácia do clotrimazol tópico versus tolnaftato tópico no tratamento da otomicose: um ensaio clínico controlado randomizado

Abstract Introduction: Otomycosis, an infection of the ear canal by fungi, is prevalent in hot and humid weather. Nevertheless, there is not sufficient evidence for the effectiveness of different topical antifungal treatments. Tolnaftate, is a topical antifungal agent described to be effective in the treatment of otomycosis. Currently there are not sufficient studies that prove its efficacy. Objectives: To compare the efficacy of clotrimazole and tolnaftate administration in the treatment of otomycosis. Material and methods: A controlled, randomized and open clinical trial included patients diagnosed with fungal external otitis who were treated with topical antifungals, randomized into two treatment groups: (1) clotrimazole cream; (2) tolnaftate solution. They were microscopically evaluated at one and two weeks of treatment to determine resolution of disease. Recurrence and complications were recorded. Demographic and clinical variables were collected and analyzed. Follow-up and final outcomes (absence of infection) were compared between groups. Results: Forty eight patients were included, 28 in the clotrimazole group and 20 in the tolnaftate group. Spring was the weather most commonly associated with otomycosis, while otic manipulation was the risk factor more common in both groups. Predominant symptoms were itching and otic fullness. Aspergillus niger organism was isolated most frequently. Treatment with clotrimazole resulted in 75% resolution vs 45% resolution with treatment with tolnaftate at one week of treatment (p = 0.007). The Tolnaftate treatment group demonstrated higher recurrence rates and treatment failures, 20% and 15% respectively. Conclusions: Clotrimazole cream treatment is more effective than tolnaftate for uncomplicated otomycosis. More studies are needed to corroborate our results.

Resumo Introdução: Otomicose, uma infecção fúngica do canal auditivo externo, é prevalente em climas quentes e úmidos. No entanto, a literatura não apresenta evidências suficientes sobre os diferentes tratamentos antifúngicos tópicos. O tolnaftato é um antifúngico tópico descrito como eficaz no tratamento da otomicose; entretanto, sua eficácia não está suficientemente comprovada. Objetivo: Comparar a eficácia do uso de clotrimazol e tolnaftato no tratamento da otomicose. Material e método: Ensaio clínico controlado e randomizado; incluiu pacientes diagnosticados com otite externa fúngica tratados com antifúngicos tópicos, randomizados em dois grupos de tratamento: 1) clotrimazole (creme); 2) solução de tolnaftato. Eles foram avaliados microscopicamente uma e duas semanas após o início do tratamento para avaliar a resolução da doença. Recorrência e intercorrências foram registradas; além disso, as variáveis demográficas e clínicas foram coletadas e analisadas. Os dados do acompanhamento e desfechos finais (ausência de infecção) foram comparados entre os grupos. Resultados: O estudo incluiu 48 pacientes, 28 dos quais foram alocados ao grupo clotrimazole e 20 ao grupo tolnaftato. A primavera foi a estação mais comum; a manipulação foi o fator de risco mais comum em ambos os grupos. Os sintomas mais comuns foram coceira e plenitude auricular. Aspergillus niger foi o micro-organismo mais comumente isolado. Após uma semana, o tratamento com clotrimazol apresentou uma taxa de resolução de 75% vs. 45% com o tratamento com tolnaftato (p = 0,007). O tratamento com tolnaftato apresentou maiores taxas de recidiva e falhas: 20% e 15%, respectivamente. Conclusões: Em casos de otomicose não complicada, o uso de clotrimazol (creme) é mais eficaz do que o de tolnaftato. Mais estudos são necessários para corroborar os presentes resultados.

Leptospirosis: vigilancia de casos del programa sindrome febril icterohemorragico . Aragua , Venezuela / Leptospirosis : surveillance of cases in the aragua hemorrhagic jaundice febrile syndrome program

La leptospirosis es una antropozoonosis de distribución mundial, con mayor incidencia en países tropicales. En Venezuela los casos son registrados en el sistema nacional de vigilancia para enfermedades íctero-hemorrágicas, con poca publicación sobre los aspectos clínicos y epidemiológicos de la enfermedad, por lo tanto el objetivo fue establecer las características epidemiológicas, clínicas, y diagnósticas de la leptospirosis en el Estado Aragua. El diseño fue un estudio epidemiológico transversal que describe los casos confirmados y probables de leptospirosis, obtenidos a partir del programa nacional de Síndrome Febril Ictérico Hemorrágico. Como resultados de 533 casos reportados desde enero del 2011 hasta julio del 2013, 233 (43,7%) fueron probables y 68 (12,75%) confirmados de leptospirosis. La tasa cruda de incidencia acumulada de leptospirosis por 100.000 habitantes más elevada en el periodo de estudio ocurrió en el año 2012, con un valor de 2,94 y los municipios con mayor tasa fueron Bolívar (7,9) y Sucre (5,2). Los factores de riesgo más reportados fueron: presencia de roedores en vivienda con 63,2%, marzo y abril, los meses con menor pluviosidad presentaron la menor frecuencia de casos. Los síntomas más frecuentes en los casos confirmados fueron fiebre 75%, cefalea 61,8%, ictericia 55,9%, vómitos 54,4%, dolor abdominal 47,1%, diarrea 35,3%. Cefalea, artralgia, mialgia y dolor retro-ocular predominaron en mayores a 10 años. 12,8% de los casos de leptospirosis se diagnosticaron por PCR en sangre, 28% PCR en orina, 45,2% por MAT.

Leptospirosis is a worldwide distribution anthropozoonosis, with a higher incidence in tropical countries. In Venezuela, the cases are registered in the national surveillance system for the ictero-hemorrhagic diseases, with little documentation upon clinical and epidemiological aspects of the disease; hence, the aim of this study was to establish epidemiologic, clinical and diagnostic characteristics of leptospirosis in Aragua state. It was a Cross sectional epidemiological study where probable and confirmed cases of leptospirosis were described, obtained from the febril icterohemorrhagic national surveillance program. From 533 cases reported since January of 2011 to July of 2013, 233 (43,79%) were probable cases, 68 (12,75%) were confirmed for leptospirosis. The highest cumulative incidence crude rate of leptospirosis per 100.000 inhabitants of the study period occurred in 2012 with 2,94. Bolivar (7,9%) and Sucre (5,2%) were the municipalities with the highest incidence rate. The main risk factors were: the presence of rodents in houses 63,2%, march and april were the months with the lowest rainfall which showed the fewest number of cases. The most frequent symptoms in confirmed cases were fever (75%), headaches (61,8%), jaundice (55,9%), vomiting (54,4%), abdominal pain (47,1%), diarrhea (35,3%), were the most frequent symptoms among confirmed cases. Headache, joint pain, myalgia, and retroocular pain, were significantly more frequent in ages over 10 years. 12,8% of the caseswere diagnosed by PCR based on blood, 28% by PCR based on urine, 45,2% by MAT.

Dermatomiositis y síndrome de Evans asociado a infección por HTLV-1 / Dermatomiositis and Evans syndrome associated with HTLV-1 infection

Paciente mujer de 55 años de edad, natural de Ayacucho, con antecedente de dermatomiositis desde hace 3 años, recibió tratamiento irregular con prednisona. Dos meses antes del ingreso presenta anemia hemolítica autoinmune y púrpura trombocitopénica idiopática, recibió pulsos de metilprednisolona y transfusión de paquetes globulares. Al ingreso, soporosa, mal estado general, marcada pérdida ponderal, deshidratada, livedo reticularis en miembros inferiores, onicodistrofia y onicolisis múltiple en los dedos de ambos pies. Western Blot positivo para HTLV-1. Evoluciona con hipoglicemia recurrente. Reportamos un caso de dermatomiositis y síndrome de Evans presentados en el contexto de una infección por virus linfotrópico humano tipo 1...

A 55-year-old female patient, born in Ayacucho, with a history of dermatomyositis for 3 years, who received irregular treatment with prednisone. Two months prior to admission, she presented with autoinmune hemolytic anemia and idiopathic thrombocytopenic purpura. The patient received methylprednisolone pulse therapy and packed red blood cells transfusions. Upon admission, she was drowsy, with a poor overall status, marked weight loss, dehydration, with presence of livedo reticularis in her lower extremities, and onychodystrophy and onycholysis on the toes of both feet. Western blot test was positive for human T-lymphotropic virus type 1 (HTLV-1). The patient evolved with recurrent hypoglycemia. Therefore, we report a case of dermatomyositis and Evans syndrome in the context of an HTLV-1 infection...

Pénfigo foliáceo endémico / Endemic pemphigus foliaceus (fogo selvagem)

El pénfigo foliáceo endémico (P F E) o fuego salvaje es una dermatosis ampollar auto inmune presente en áreas de la Amazonia peruana. Se caracteriza por vesículas intraepidérmicas acantolíticas, localizadas en la región subcorneal y en cuya etiología participan anticuerpos contra desmogleína 1, una glicoproteína encargada de la unión intercelular de las células epidérmicas. Se presenta el caso de en una mujer de 52 años con PFE grave, de evolución fulminante y desenlace fatal por sepsis...

The endemic pemphigus foliaceus (EPF) or fogo selvagem is an autoimmune bullous dermatosis located in areas of our Amazon jungle .It is characterized by intraepidermic acantholytic vesicles in the subcorneal region and its etiology involves the presence of antibodies to desmoglein 1, a glycoprotein responsible for the intercellular junctions of the epidermal cells. We present the case of a 52-year-old woman with severe PFE with fulminant evolution and fatal outcome due to sepsis...

Acción analgésica y neurofarmacológica de las fracciones soluble y no soluble del extracto etanólico de la semilla de Jatropha curcas L. / Analgesic and neuropharmacological activities of soluble and not soluble fractions of the ehtanolic extract from Jatropha curcas L. seeds

Introducción. Estudios preclínicos evidencian efectos dosis dependiente sobre la analgesia e inflamación y neurotoxicidad de las hojas, corteza y raíz de J. curcas L. El propósito del estudio fue evaluar la actividad analgésica y neurofarmacológica de las fracciones de la semilla de J. curcas L. Métodos. Estudio experimental, preclínico y prospectivo. Se distribuyeron 48 ratones en seis grupos control: ácido acético, diclofenaco, tramadol, agua destilada, diazepam y cafeína. Cuatro grupos experimentales: fracción soluble a 500 mg/kg y fracción no soluble a 250, 500 y 750 mg/kg; se evaluó los efectos sobre la algesia, por medio de la prueba de contorsiones abdominales por ácido acético a 1,5 %, y las manifestaciones neurológicas, mediante la prueba de Irwin. Se realizaron pruebas para el análisis de las variables cuantitativas y para las variables cualitativas. Resultados. La inhibición de las contorsiones fue 62,27 %, 56,86 %, 44,12 % y 42,06 % para los grupos 5, 2, 4 y 3, respectivamente. Las manifestaciones neurológicas de los grupos experimentales mostraron presencia y significancia de las variables excitación, sacudidas de cabeza, rascarse, incoordinación motora, cola de Straub, piloerección y estereotipias. Las variables estereotipias y rascado se presentaron en las dos fracciones. Conclusión. La fracción soluble y la no soluble del extracto etanólico de J. curcas L. presentaron efecto analgésico y efectos tóxicos a nivel del sistema nervioso central.

Introduction. Preclinical studies show the dose dependent effects on the analgesia, inflammation and neurotoxicity of the leaves, bark and root. The purpose of the study was to evaluate the analgesic and neuropharmacological activity of the fractions of the seed J. curcas L. Methods. Experimental study, preclinical and prospective. 48 rats were distributed in 6 control groups: acetic acid, diclofenac, tramadol, distilled water, diazepam, caffeine. Four experimental groups: 500 mg/kg of soluble fraction and 250, 500 y 750 mg/kg of insoluble fraction; the effects on the algesia were evaluated using an exam of abdominal contortions with acetic acid on 1,5%; the neurological manifestations were measured with the Irwin test. To analyze the quantitative and qualitative variables exams were used. Results. The inhibition of the contortions were 62,27 %, 56,86 %, 44,12 % y 42,06 % for the groups 5, 2, 4 y 3, respectively. The neurological manifestations of the experimental groups showed the presence and significance of the variables: excitation, head twitches, scratching, motor incoordination, Straub tail, piloerection and stereotypies. The variables stereotypes and scratching presented themselves in the two fractions. Conclusion. The soluble and insoluble fraction of the ethanoic extract of J. Curcas L. presented analgesic and toxic effects on the central nervous system.

Mecanismos de interacción entre el extracto etanólico de Jatropha curcas L. y metoclopramida en el sistema gastrointestinal / The mechanisms of interaction between the ethanol extract of Jatrohpa curcas L. and metoclopramide on gastrointestinal system

Objetivo: Determinar los mecanismos de interacción entre el extracto etanólico de Jatrohpa curcas L. y la metoclopramida sobre el sistema gastrointestinal. Material y Métodos: Se usó 30 ratones albinos machos, en5 grupos; los que recibieron por vía oral: Grupo 1: Jatropha curcas L. 800 mg/Kg, y 0, 5mg/Kg de metoclopramida. Grupo 2: 0.5 mg/mL de metoclopramida. Grupo 3: 1.5 mg/Kg de Atropina. Grupo 4: 800 mg/kg de Jatropha curcas L. Grupo 5: no recibió medicamento. A todos, se les administró por vía oral: carbón activado al 5% 0,1 mL/10g, como marcador intestinal. Se empleó el Método Arboset al, para evaluar la motilidad intestinal. La validación estadística del recorrido intestinal se realizó aplicando las pruebas de Kolmogorov Smirnov, ANOVA de 1 cola, Tukey y Newman-Keuls. Resultados: Se observó un el porcentaje de recorrido del carbón de 36.46% del grupo 1 frente a 65,45%, 3,66% y 58,87% de los grupos 2, 3 y 4, respectivamente; y de 58,87% del grupo 4 frente a 20,94% del grupo 5. Conclusiones: Se evidenció el antagonismo entre el extracto etanólico de la semilla de Jatropha curcas L. con la metoclopramida, el cual se explicaría por la interacción entre el sistema colinérgico, adrenérgico, GABAérgico y de neuropéptidos sobre la glándula suprarrenal, sistema nervioso central y gastrointestinal.

Objective: Determinate the mechanisms of interaction between the ethanol extract of Jatrohpacurcas L. and metoclopramide on gastrointestinal system. Material and Methods: 30 male albino mice were used, forming 5 groups and received oral medications as follows: Group 1: Jatropha curcas L. 800 mg / kg, and 0.5 mg/Kg of metoclopramide. Group 2: 0.5 mg/mL of metoclopramide. Group 3: 1.5 mg/Kg of atropine. Group 4: 800 mg/Kg of Jatropha curcas L. Group 5 received no medication. All groups receivedoral activated charcoal 0.1 mL/10g as intestinal marker. The Arbos et al method was used to evaluate intestinal motility. The statistical validation of the intestine dynamics was performed using the Kolmogorov Smirnov, 1-tailed ANOVA, Tukey and Newman-Keuls. Results: the percentage of charcoal runs in the 1rst group was 36.46% compared to 65.45%, 3.66 % and 58.87% for the 2nd, 3th and 4th groups, respectively. In the 4th group was 58,87% compared to 20.94% in the 5th group. Conclusions: the antagonism between the ethanol extract of the seeds of J.curcas L. with metoclopramide, which is probably would explain by the interaction between the cholinergic system, adrenergic system, GABAergic system and neuropeptides on the adrenal gland, central nervous system and gastrointestinal system.

Dosis-respuesta sobre la motilidad intestinal y el sistema nervioso de la interacción entre Jatropha curcas L. y metoclopramide / Intestinal motility andnervous system effects dose-response curvefor the interaction between Jotropha curcas L. and metoclopramide

Objetivo: Determinar el efecto dosis-respuesta sobre la motilidad intestinal y el sistema nervioso, de la interacción entre el extracto etanólico de las semilla de J. curcas L. y metoclopramida. Métodos: Se utilizaron 90 ratones albinos,formando 10 grupos de interacción que recibieron por vía oral (VO), en dosis establecida metoclopramida 0,5 mg/kg y en dosis escalonada extracto etanólico de la semilla de J. curcas L. (100 a 1000 mg/kg). Otros 5 grupos recibieron por VO, 0,5 mg/kg de metoclopramida; 1,5mg/kg de atropina; 800mg/kg de J. curcas L., 0,1ml/10g de agua destilada y el último grupo no recibió medicamento. A todos los grupos, se les administró vía oral carbón activado al 5 %, 0,1ml/10 g, como marcador intestinal. Se empleó el Método de Arbos et al, para evaluar la motilidad intestinal y la prueba de Irwin para el sistema nervioso. La validación estadística del recorrido intestinal se realizó aplicando las pruebas de Shapiro-Wilk, ANOVA de 1 cola, Tukey, Newman-Keuls, Kruskal-Wallis y correlación de Pearson. Para la prueba de Irwin se aplicó la prueba de Chi-cuadrado corregido de Yate y el estadístico exacto de Fisher. Resultados: Se observó un porcentaje de recorrido del carbón de 56,8%, 34,54%, 31,85% y 24,57%, en los grupos de interacción 2, 7, 8, 9 y 10 respectivamente, frente a 56,3% (metoclopramida) y 27,66% (control). El Test de Irwin denotó piloerección, sedación, aumento de la respiración y letalidad. Conclusiones: Se comprobó el antagonismo entre el extracto etanólico de la semilla de J. curcas L. con la metoclopramida, y la ocurrencia de manifestaciones en el sistema nervioso.

Objectives: Determinate the dose-response relationship with respect to intestinal motility and the nervous system, of the interaction between the ethanol extract of the J. curcas L. seed and metoclopramide Methods: 90 albino mice were used, which were divided into 10 interaction groups that received 0.5 mg Kg oral (PO) metoclopramide as a fixed dose, and they also received progressively increased doses (100 to 1000 mg/Kg) of an ethanol extract of J. curcas L. seeds. Five additional groups received 0.5 mg metoclopramide PO, 1.5 mg/Kg atropine, 800 mg/Kg J. curcas L., and 0.1 ml/10g distilled water. All groups received oral 5% activated charcoal, 0.1 ml/10g as an intestinal marker. We used the technique described by Arbos et al. for assessing intestinal motility and Irwin's test for assessing the nervous system. The statistical validation of intestine dynamics was performed using Shapiro-Wilk, 1-tailed ANOVA, Tukey, Newman-Keuls, Kruskal-Wallis and Pearson correlation tests. We used the Chi-square method with Yates correction and Fisher's exact method when performing Irwin's test. Results: The percentages of charcoal runs in the 2nd, 7th, 8th, 9th, and 10th interaction groups were 56.8%, 34.54%, 31.85 and 24.57%, compared to 56.3% (metoclopramide) and 27.66% (control). The Irwin test showed these neurological effects: piloerection, sedation, increased respiratory rate and lethality. Conclusions: We proved there is antagonism between the ethanol extract of J. curcas L. seeds and metoclopramide. We also found the concomitant occurrence of neurotoxic effects.

Delayed administration of G-CSF until day +7 after autologous peripheral blood stem cell transplant is as effective in accelerating hematopoietic as day 0

PURPOSE: To compare the hematopoietic recovery and the clinical outcome after high dose chemotherapy and peripheral blood stem cell (PBSC) transplant between patients who received recombinant granulocyte colony-stimulating factor (G-CSF) starting on day 0 and those who received it starting on day +7. PATIENTS AND METHODS: Thirty-five consecutive patients received high dose chemotherapy with ifosfamide, etoposide and carboplatin (ICE) and autologous PBSC transplant. PBSC mobilization was achieved with G-CSF. In 19 transplants done in 1994, G-CSF was started on day 0 and in 16 procedures done in 1995, G-CSF was started on day +7. In both groups G-CSF was given until the absolute neutrophil count was 1 x 10(9)/L. RESULTS: The median number of days to reach an absolute neutrophil count > 0.1 x 10(9)/L, was 11 in the patients who started the G-CSF on day 0 and 11 days in the patients with delayed administration of G-CSF and to reach > 0.5 x 10(9)/L 14 days and 13 respectively. The median number of days to reach a platelet count > 20 x 10(9)/L was 14 and 13. Comparison of early vs. delayed administration of G-CSF did not show any significant differences regarding the time to achieve platelet independence, number of days with fever, median days of hospital stay, number of red cell or platelet transfusions. CONCLUSIONS: Starting G-CSF on day +7 after high dose ICE chemotherapy and autologous transplant of PBSC is as effective in restoring the hematopoietic function as is starting its administration on day 0.

Bioavailability of etoposide after oral administration of the solution marketed for intravenous use: Therapeutic and pharmacoeconomic perspectives

Background. Oral etoposide administration is a suitable alternative to the intravenous route; therefore, commercial capsules have been developed. Before these capsules were available in Mexico, we studied drug bioavailability after oral administration of the intravenous etoposide solution (IVES). Methods. Eight adult cancer patients received a 50-mg oral etoposide dose as IVES and blood samples were collected over a period of 24 h. plasma etoposide concentration was determined by high-performance liquid chromatography, plasma concentration against time curves were constructed, and biovailability parameters were calculated. Results. Oral IVES yielded an adequate bioavailability profile because Cmax was 2.38 ñ 0.30 µg/mL, AUC was 12.87 ñ 2.02 µg/mL and half-life was 6.72 ñ 0.97 h. Conclusions. Considering that the pharmacokinetic aim is to maintain plasm concentrations between 0.5 and 1.0 µg/mL for several hours while avioding high concentrations, i.e., of 10 µg/mL or higher, oral administration of 50-mg etoposide as IVES appears to be a suitable dosing option. In addition, oral IVES is considerably less expensive than intravenous administration in terms of both drug presentation and administration