Análise ultraestrutural do colágeno de feridas cutâneas de coelhos tratadas com plasma rico em plaquetas de equino / Ultrastructural analysis of the collagen of rabbit skin wounds treated with platelet-rich equine plasma

O colágeno é sintetizado e segregado no espaço extracelular e organizados em fibrilas estriadas de acordo com o tipo de tecido. Utilizaram-se 24 coelhos brancos da raça Nova Zelândia, com idade de 12 meses e com 3,0kg de peso corporal, para avaliar a porcentagem de colágeno das feridas cutâneas tratadas com plasma rico em plaquetas de equino e pomada contendo gentamicina, sulfanilamida, sulfadiazina, ureia e vitamina A. Os animais foram separados em quatro grupos de igual número e submetidos à remoção de pele na região das linhas médias dorsal torácica (feridas tratadas) e lombar (feridas controle). As feridas torácicas foram tratadas com plasma rico em plaqueta de equino e pomada contendo gentamicina, sulfanilamida, sulfadiazina, ureia e vitamina A, e as do grupo controle somente com a pomada. Dos animais do grupo I, foi coletado tecido cutâneo, para a avaliação histológica e a ultraestrutural, com três dias de pós-operatório; dos animais do grupo II, com sete dias; do grupo III, com 14 dias; e do grupo IV, com 21 dias. Decorrido o período de avaliação de cada grupo, foi coletado fragmento de pele para avaliação da porcentagem de colágeno, bem como do diâmetro e da densidade da fibrila de colágeno por microscopia eletrônica de transmissão. O tratamento com PRP de equino associado à aplicação tópica da pomada mostrou-se eficaz na maturação das fibrilas colágenas e na antecipação do processo cicatricial.(AU)

Collagen is synthesized and secreted into the extracellular space and organized into striated fibrils according to the tissue type. This study evaluated the concentration of collagen in rabbit skin wounds treated with equine platelet-rich plasma (PRP) and ointment containing gentamicin, sulfanilamide, sulfadiazine, urea, and vitamin A. Twenty-four New Zealand white rabbits aged 2 to 12 months and weighing 3.0kg were included. The animals were allocated equally into four groups and the skin was removed from the thoracic dorsal midline (treated wound) and lumbar (control wound) regions. The thoracic wounds were treated with equine PRP and ointment containing gentamicin, sulfanilamide, sulfadiazine, urea, and vitamin A, and the control group was treated with the ointment alone. For histological and ultrastructural assessment, cutaneous tissue was collected on postoperative days 3 (group I), 7 (group II), 14 (group III), and 21 (group IV). After the evaluation period, in each group, a skin fragment was collected for analysis of the collagen concentration, as well as the collagen fibril diameter and density by transmission electron microscopy. The results indicated that treatment with equine PRP combined with topical application of the ointment was effective in facilitating the maturation of collagen fibrils and the wound healing process.(AU)

Association of intraperitoneal ceftriaxone, intravenous gentamicin and oral metronidazole in the treatment of an abdominal abscess and peritonitis in a horse: case report / Associação da ceftriaxona intraperitoneal, gentamicina intravenosa e do metronidazol oral no tratamento de abscesso abdominal e peritonite em equino: relato de um caso

Medical management of abdominal abscesses in horses requires prolonged antibiotic therapy and presents varied success rates. A 6-year-old male horse with a history of colic and multiple abdominal punctures to relieve gas was attended. At admission, tachycardia, tachypnea, hyperthermia, mucosal congestion, dehydration, and rigid gait were observed. The association of physical examination, laboratory and ultrasonographic findings allowed the diagnoses of peritonitis and abdominal abscess. Supporting treatment plus broad spectrum antibiotic therapy was performed: daily intraperitoneal ceftriaxone (25 mg/kg, 7 days); daily intravenous gentamicin (6.6 mg/kg, 7 days); per os metronidazole three times a day (15 mg/kg 12 days), followed by the same dose twice a day (15 mg/kg 33 days), totaling 45 days of treatment. Plasma fibrinogen and ultrasonographic examination were the most effective tools to evaluate abscess evolution. There was normalization of the physical examination 24 h after beginning the treatment, consecutive regression of the nucleated cell count in the peritoneal fluid, and regression of plasma fibrinogen and size of the abscess. On the 10th treatment day, the animal was discharged from the hospital, maintaining oral therapy with metronidazole every 12 h (15 mg / kg). When the animal returned on the 30th day, an abscess size regression was observed. However, there was no resolution, and therapy with metronidazole was maintained. On the 45th day of treatment, a new hospital evaluation was performed, where the abscess resolved, and metronidazole was suspended. It is highlighted that the therapeutic association used in the treatment of abdominal infection and abscess resulted in a rapid clinical response.(AU)

O tratamento conservativo dos abscessos abdominais em equinos requer antibioticoterapia prolongada e apresenta variadas taxas de sucesso. Foi atendido um cavalo de seis anos de idade, com histórico de cólica e múltiplas punções abdominais por agulha para esvaziamento de gás. Na admissão, foram observados taquicardia, taquipnéia, hipertermia, congestão mucosa, desidratação e marcha rígida. A associação do exame físico, achados laboratoriais e ultrassonográficos permitiu o diagnóstico de peritonite e abscesso abdominal. Foi realizado tratamento suporte e antibioticoterapia de amplo espectro: ceftriaxona intraperitoneal diária (25 mg/kg, 7 dias); gentamicina intravenosa diária (6,6 mg/kg, 7 dias); metronidazol oral três vezes ao dia (15 mg/kg, 12 dias), seguido de mesma dose duas vezes ao dia, por mais 33 dias, totalizando 45 dias de tratamento. O fibrinogênio plasmático e o exame ultrassonográfico foram os recursos mais eficazes para a avaliação da evolução do abscesso. Após 24 horas do início do tratamento foi constatada a normalização do exame fisico, regressão progressiva da contagem de células nucleadas no líquido peritoneal, do fibrinogênio plasmático e do tamanho do abscesso. No 10° dia de tratamento o animal recebeu alta hospitalar, mantendo-se a terapia oral com metronidazol a cada 12 horas (15 mg/Kg). Em retorno, ao 30° dia, observou-se regressão do tamanho do abscesso, entretanto, não houve resolução, tendo sido mantida a terapia com metronidazol. No 45º dia de tratamento, realizou-se nova avaliação hospitalar, onde foi observada a resolução do abscesso e a admnistração do metronidazol foi suspensa. Destaca-se, que a associação terapêutica utilizada no tratamento de infecção abdominal e abscesso resultou em rápida resposta clínica.(AU)

Luxación erecta expuesta de hombro en un niño: reporte de un caso / Erect shoulder dislocation in a child: case report / Erecto luxação do ombro em uma criança: relato de caso

La luxación erecta expuesta de hombro es una asociación lesional de muy baja frecuencia en la edad pediátrica. Son más frecuentes las lesiones fisarias y epifisarias que las luxaciones y lesiones ligamentarias. Esto es debido a la presencia de un tejido óseo con gran poder de deformidad elástica y un periostio grueso. Presentamos un caso clínico de un paciente de 11 años de edad que sufrió una luxación erecta expuesta de hombro derecho, producto de una caída de 1 metro y medio de altura. El tratamiento consistió en una limpieza quirúrgica de urgencia, reducción gleno humeral y antibioticoterapia empírica, penicinila 400.000 UI/kg/día fraccionado cada 6 hs y gentamicina 3mg/Kg/día fraccionada cada 8 h por 10 días, inmovilización por 3 semanas con cabestrillo seguido de rehabilitación, y un follow up de 2 años al final del cual el paciente no presento secuelas funcionales en la articulación glenohumeral derecha.

The exposed erect dislocation of the shoulder is a very low frequency lesion association in the pediatric age. The physical and epiphyseal lesions are more frequent than the dislocations and ligament injuries. This is due to the presence of a bone tissue with great elastic deformity power and a thick periosteum. We present a clinical case of an 11-year-old patient who suffered an exposed erect dislocation of the right shoulder, due to a fall of 1 meter and a half high. The treatment consisted of emergency surgical cleaning, humeral gleno reduction and empirical antibiotic therapy, penicinila 400,000 IU/kg/day divided every 6 hours and gentamicin 3mg/Kg/day divided every 8 hours for 10 days, immobilization for 3 weeks with a sling followed by rehabilitation, and a follow-up of 2 years at the end of which the patient did not present functional sequelae in the right glenohumeral joint.

A luxação ereta exposta do ombro é uma associação de lesão de freqüência muito baixa na idade pediátrica. As lesões físicas e epifisárias são mais freqüentes que as luxações e lesões ligamentares. Isto é devido à presença de um tecido ósseo com grande poder de deformidade elástica e um periósteo espesso. Apresentamos um caso clínico de um paciente de 11 anos de idade que sofreu uma luxação ereta exposta do ombro direito, devido a uma queda de 1 metro e meio de altura. O tratamento consistiu em limpeza cirúrgica de emergência, redução de gleno umeral e antibioticoterapia empírica, penicinila 400.000 UI / kg / dia dividida a cada 6 horas e gentamicina 3mg / Kg / dia dividida a cada 8 horas por 10 dias, imobilização por 3 semanas com tipóia seguida de reabilitação e seguimento de 2 anos no final dos quais o paciente não apresentava sequela funcional na articulação glenoumeral direita.

Uso de gentamicina transtimpánica: experiencia del Hospital Clínico de la Universidad de Chile / Transtympanic gentamicin: experience in Hospital Clínico Universidad de Chile

RESUMEN Introducción: La gentamicina transtimpánica se utiliza en el manejo de pacientes con vértigo crónico refractario al manejo médico. Objetivo: Describir y analizar las características clínicas, epidemiológicas, y resultados de pacientes sometidos a tratamiento con gentamicina transtimpánica en el Hospital Clínico de la Universidad de Chile. Material y método: Estudio retrospectivo, descriptivo, incluyendo los pacientes con patología otorrinolaringológica que hayan recibido gentamicina transtimpánica entre los años 2008 y 2018. Se analizaron variables epidemiológicas, clínicas, y función vestibular. Resultados: La serie está constituida por diez pacientes, con una edad promedio de 52,4 años; siete mujeres y tres hombres. El diagnóstico fue en su mayoría enfermedad de Ménière (7 pacientes). El número promedio de inyecciones de gentamicina fue de 2,8. En el período de seguimiento (rango 1-96 meses), se logró mejoría del vértigo en la mayoría de los pacientes (8 de 10). Conclusión: El tratamiento con inyecciones de gentamicina transtimpánica es una opción importante para aliviar la sintomatología de pacientes con vértigo crónico intratable. Debe indicarse en casos seleccionados, y siempre realizar un estudio auditivo y vestibular completo antes y después del tratamiento con gentamicina.

ABSTRACT Introduction: Transtympanic gentamicin is used for treatment of patients with chronic vertigo refractory to medical management. Aim: To describe and analyze the clinical outcome of patients whom underwent treatment with transtympanic gentamicin at the Clinical Hospital Universidad de Chile. Material and method: Retrospective and descriptive study including patients with otolaryngologist disease whom underwent treatment with transtympanic gentamicin between 2008 and 2018. Epidemiological, clinical variables and vestibular function were analyzed. Results: The serie consists of ten patients, 7 men and 3 women, with an average age of 52,4 years. The most frequent diagnosis was Ménière disease (7 patients). The average number of gentamicin injections was 2,8. The follow up varies from 1 to 96 months, presenting improvement of vertigo in the majority of the cases (8 of 10 patients). Conclusion: The treatment with transtympanic injections of gentamicin is a relevant option to decrease symptoms in patients with chronic intractable vertigo. It should be indicated in selected patients. Prior and posterior the treatment, patients must be studied with a complete evaluation of the auditory and vestibular function.

Diverticulitis cecal: un complejo desafío médico / Cecal diverticulitis: a complex medical challenge

Antecedentes: la diverticulitis cecal es una patología poco común en los países occidentales. Clínicamente es indistinguible de una apendicitis aguda. Objetivos: exhibir los resultados de acuerdo con diferentes abordajes terapéuticos. Material y métodos: se presentan cinco casos de diverticulitis cecal tratados en nuestra institución entre enero de 2013 y diciembre de 2015. Revisión retrospectiva de historias clínicas e imágenes. Revisión de la literatura. Resultados: fueron incluidos cinco pacientes. En cuatro hubo resolución quirúrgica y uno tuvo buena evolución con tratamiento médico. Conclusiones: si bien es poco frecuente, la diverticulitis cecal debe considerarse dentro de los diagnósticos diferenciales frente a un cuadro de dolor abdominal localizado en fosa ilíaca derecha acompañado de estudios por imágenes no categóricos de apendicitis aguda.

Background: cecal diverticulitis is a rare disease in western countries. It is clinically indistinguishable from acute appendicitis. Objetive: to show outcome with different therapeutic approaches. Material and methods: we present five cases of cecal diverticulitis treated at our institution between January 2013 and December 2015. Retrospective review of medical records and images. Review of the literature. Results: five patients were included. Four cases required surgical treatment while one patient resolved with medical treatment. Conclusions: Although it is rare, cecal diverticulitis must be considered within the differential diagnoses in the face of abdominal pain located in the right iliac fossa and non-categorical imaging of acute appendicitis.

Intratympanic Gentamicin for Intractable Ménière's Disease - A Review and Analysis of Audiovestibular Impact

Abstract Introduction Intratympanic gentamicin regulates the symptoms in most patients with incapacitating Ménière's disease. The treatment protocols have changed over the years from medical labyrinthectomy to preservation of vestibular function. Objectives This study aims to review the audiovestibular response related to the effect of the drug in controlling vertigo. Data Synthesis Articles were identified by means of a search in the PubMed database using the key words Meniere and intratympanic or transtympanic gentamicin. Total 144 articles were reviewed after excluding those that were technical reports, those based on experimental animal studies, those that focused on outcomes other than vertigo (tinnitus or aural fullness), those with delivery methods other than tympanic membrane injection, and those with bilateral cases. If there was more than one article by the same author(s) or institution, only the most recent one matching the aforementioned criteria and those that were not overlapping were included. Conclusion Titration methods or multiple injections on a daily basis can be preferred if the patients have profound or non-serviceable hearing, since these methods have significant incidence of hearing loss. Treatment protocols with a frequency of injection not shorter than once a week, or those with injections on a monthly basis as "needed" provide the same level of vertigo control with better preservation of hearing. Caloric testing is not an ideal tool to analyze the correlation between vertigo control and the effect of gentamicin as compared with gain asymmetry of the vestibulo-ocular reflex. Vestibular-evoked myogenic potentials and the head thrust test are more reliable than other vestibular tests for the follow-up of patients undergoing gentamicin treatment.

Brucelosis en Chile: descripción de una serie de 13 casos / Brucellosis in Chile: description of a series of 13 cases

Introduction: Brucellosis is a zoonosis caused by Brucella spp. It may be acquired by consuming unpasteurized dairy products. Brucellosis has a low incidence in Chile, thus, we have a scarce data. Aim: To report and to characterize the first series of clinical cases of adult patients diagnosed with brucellosis in Chile. Methods: We describe a series of 13 clinical cases in patients diagnosed between 2000 and 2016 in three different centers in the Metropolitan Region, Chile. A retrospective analysis was performed on clinical presentation, laboratory, antibiotic treatment, morbidity and mortality. Results: The mean age was 50 years old. Eight cases had a record of consumption of unpasteurized dairy products. The most frequently reported complaints were fever. The most frequent focal point involved was the spine. Only one patient had a positive blood culture, while the diagnosis was made using serological techniques in the other part of the group. The most indicated antibiotic regimens were doxycycline-rifampicin and doxycycline-gentamicin. The hospital stay was 20 days approximately as an average. Clinical cure was achieved in all cases. Conclusions: Brucellosis is an infrequent zoonosis in Chile, and it produces a nonspecific clinical picture, so it is necessary to have high suspicion to make the diagnosis based in the antecedent of consumption of unpasteurized dairy or raw meat.

Introducción: La brucelosis es una zoonosis provocada por Brucella spp, cuyo principal mecanismo de transmisión es mediante el consumo de lácteos no pasteurizados. Es de baja ocurrencia en Chile, por lo que los datos locales son escasos. Objetivo: Reportar y caracterizar la primera serie de casos clínicos de pacientes adultos con diagnóstico de brucelosis en Chile. Material y Método: Se describe una serie de 13 casos clínicos en pacientes diagnosticados entre el año 2000 y el 2016 en tres centros de la Región Metropolitana, Chile. Se realizó un análisis retrospectivo acerca de la presentación clínica, laboratorio, tratamiento antimicrobiano y morbi-mortalidad. Resultados: El promedio de edad fue 50 años. Ocho casos tenían antecedente de consumo de lácteos no pasteurizados. El motivo de consulta más frecuente fue sensación febril. El compromiso focal más frecuente fue el de columna vertebral. Sólo en un paciente se encontró hemocultivo positivo; en el resto el diagnóstico se hizo mediante técnicas serológicas. Los esquemas antimicrobianos más indicados fueron doxiciclina-rifampicina y doxiciclina-gentamicina. La estadía hospitalaria fue en promedio de 20 días. En todos los casos se logró curación clínica. Conclusiones: La brucelosis es una zoonosis infrecuente en Chile, produce un cuadro clínico inespecífico, por lo que se debe tener una alta sospecha para realizar el diagnóstico, basada en el antecedente del consumo de productos lácteos no pasteurizados o de carne mal cocida.

Refractory episodic vertigo: role of intratympanic gentamicin and vestibular evoked myogenic potentials / Vertigem refratária episódica: papel da gentamicina intratimpânica e potencial evocado miogênico vestibular

Abstract Introduction: Even today, the treatment of intractable vertigo remains a challenge. Vestibular ablation with intratympanic gentamicin stands as a good alternative in the management of refractory vertigo patients. Objective: To control intractable vertigo through complete saccular and horizontal canal vestibular ablation with intratympanic gentamicin treatment. Methods: Patients with refractory episodic vertigo were included. The inclusion criteria were: unilateral ear disease, moderate to profound sensorineural hearing loss, and failure to other treatments. Included patients underwent 0.5-0.8 mL of gentamicin intratympanic application at a 30 mg/mL concentration. Vestibular ablation was confirmed by the absence of response on cervical vestibular evoked myogenic potentials and no response on caloric tests. Audiometry, electronystagmography with iced water, and vestibular evoked myogenic potentials were performed in all patients. Results: Ten patients were included; nine patients with Meniere's disease and one patient with (late onset) delayed hydrops. Nine patients showed an absent response on vestibular evoked myogenic potentials and no response on caloric tests. The only patient with low amplitude on cervical vestibular evoked myogenic potentials had vertigo recurrence. Vertigo control was achieved in 90% of the patients. One patient developed hearing loss >30 dB. Conclusions: Cervical vestibular evoked myogenic potentials confirmed vestibular ablation in patients treated with intratympanic gentamicin. High-grade vertigo control was due to complete saccular and horizontal canal ablation (no response to iced water in electronystagmography and no response on cervical vestibular evoked myogenic potentials).

Resumo Introdução: Ainda hoje, o controle da vertigem intratável permanece um desafio. A ablação vestibular com gentamicina intratimpânica permanece como uma boa alternativa no tratamento de pacientes com vertigem refratária. Objetivo: Controlar a vertigem intratável por meio de ablação vestibular completa dos canais sacular e horizontal com gentamicina intratimpânica como tratamento. Método: Pacientes com vertigem refratária episódica foram incluídos. Os critérios de inclusão foram doença unilateral da orelha, perda auditiva neurossensorial de moderada a profunda e fracasso com outros tratamentos. Os pacientes incluídos receberam uma aplicação de 0,5-0,8 mL de gentamicina intratimpânica com concentração de 30 mg/mL. A ablação vestibular foi confirmada pela ausência de resposta no teste de potencial evocado miogênico vestibular cervical (PEMVc) e nenhuma resposta nas provas calóricas. Audiometria, eletronistagmografia com água gelada e potencial evocado miogênico vestibular foram realizados em todos os pacientes. Resultados: Ao todo, dez pacientes foram incluídos: nove com doença de Ménière e um com hidropisia tardia. Nove pacientes apresentaram ausência de resposta no teste de potencial evocado miogênico vestibular e nenhuma resposta na prova calórica. O único paciente com baixa amplitude no PEMVc apresentou recorrência da vertigem. O controle da vertigem foi obtido em 90% dos pacientes. Um paciente desenvolveu perda auditiva > 30 dB. Conclusões: O PEMVc confirmou ablação vestibular nos pacientes tratados com gentamicina intratimpânica. O alto grau de controle da vertigem foi devido à ablação completa do sáculo e canal horizontal (sem resposta à água gelada na eletronistagmografia e ausência de resposta no PEMVc).

Priming previne a insuficiência renal aguda nefrotóxica através da estimulação do mecanismo de defesa antioxidante / Priming prevent nephrotoxic acute renal failure through stimulation of antioxidant defense mechanism

RESUMO Introdução: Priming é um mecanismo de proteção induzida pela exposição anterior de uma célula ou órgão a baixas ou mesmas concentrações de uma substância tóxica. Objetivo: analisar o mecanismo de priming induzido pela exposição a gentamicina em células tubulares proximais humanas e na insuficiência renal aguda (IRA). Métodos: Células tubulares foram expostos a 2 mM de gentamicina durante 24 horas, enquanto ratos Wistar foram expostas a 40 mg/kg durante 3 dias. Depois de uma semana, as células foram expostas à mesma concentração durante 24h e os ratos durante dez dias. Os animais condicionados foram comparados com ratos controle e tratados com gentamicina durante 10 dias. Foram analisados parâmetros bioquímicos, o estresse oxidativo foi analisado por hidroperóxidos e proteínas carboniladas urinárias, enquanto a defesa antioxidante foi estudada pela atividade antioxidante do plasma e imunomarcação e atividade da catalase, superóxido dismutase, heme oxigenase-1 (HO-1) nos rins. Necrose, apoptose, proliferação e expressão da endotelina-1 (ET-1) e HO-1 foram estudadas em células. Resultados: o condicionamento dos animais inibiu o aumento da creatinina, ureia, excreção urinária de sódio e de proteína induzida por gentamicina. Bosentana, antagonista do receptor ET-1, e hemin, indutor de HO-1, potencializaram a inibição. O mecanismo de proteção foi mediado pela indução de enzimas antioxidantes HO-1, catalase e SOD atividade e redução do estresse oxidativo. O condicionamento inibiu a morte celular e induziu a proliferação via produção de ET-1. Conclusão: o mecanismo de condicionamento é persistente e multifactorial, o estímulo da defesa antioxidante poderia mimetizar o processo de condicionamento e impedir a IRA.

ABSTRACT Introduction: Priming is the mechanism of protection induced by a previous exposition of a cell or organ to low or equal concentrations of a toxic substance. Objective: To analyze the mechanism of priming induced by the previous exposition to gentamicin in human proximal tubular cells and nephrotoxic acute renal failure (ARF). Methods: Wistar rats and tubular cells were exposed to gentamicin 2mM during 24h or 40 mg/kg during 3 days and after one rest week were exposed to the same concentration during 24h in cells and additional ten days in rats. The primed animals were compared to control rats receiving vehicle and GENTA animals treated with the gentamicin during the same period. Biochemical parameters were analyzed. The oxidative stress was analyzed by urinary hydroperoxides and carbonylated protein while antioxidant defense was studied by antioxidant activity of the plasma (FRAP), catalase, superoxide dismutase, heme-oxygenase 1 (HO-1) immunostaining and enzymatic activity in kidney. Necrosis, apoptosis, proliferation, endothelin 1 (ET-1) and HO-1 expression were studied in cells. Results: Priming of the animals inhibited the increase in creatinine, urea, sodium excretion and urinary protein induced by gentamicin. Bosentan, ET-1 receptor antagonist, and hemin, HO-1 inducer, potentiate the inhibition. The mechanism of protection was mediated by induction of the antioxidant enzymes HO-1, catalase and SOD activity and oxidative stress reduction. Priming inhibited cell death and induced proliferation through ET-1 production. Conclusion: Priming is a persistent and multifactorial mechanism, the stimulation of the antioxidant defense could mimics partially the priming process and prevent the ARF.

Parámetros farmacocinéticos de gentamicina en recién nacidos de término: ¿Es necesario monitorizar en forma sistemática sus concentraciones plasmáticas? / Gentamicin pharmacokinetics in term newborn: ¿Is it necessary to systematically monitor plasmatic levels?

Background: Gentamicin is indicated as empiric treatment for neonatal sepsis. Plasmatic levels dosification of gentamicin is a common practice. The relationship between peak plasma concentration (Cmáx) with minimum inhibitory concentration (MIC) (Cmáx/MIC) is the parameter that best predicts treatment efficacy. Aim: To determine pharmacokinetics of gentamicin in term newborn infants. Methods: Term newborn infants receiving gentamicin, without critical illness in which plasmatic levels of gentamicin was performed were included. Elimination clearance (Cl) elimination half-life (t½) and volume of distribution (Vd) were calculated. In each case the value of Cmax/MIC parameter was calculated, considering a MIC value of 1 μg/mL for Escherichia coli. Results: Thirteen newborns were included. The mean PK values were Cl: 0.26 mL/hour, Vd: 0.54 L/kg and t½: 6.8 h. Cmax/MIC was > 8 in 6 newborns. Conclusions: Pharmacokinetic parameters of gentamicin are predictable in term newborn infants. With gentamicin doses normally used Cmax/MIC values reached 8 in 6 newborns. It is necessary to review the usefulness of plasma drug monitoring and gentamicin dosage in this group of newborns.

Introducción: Gentamicina es utilizada como tratamiento empírico en la sepsis neonatal. El monitoreo de su concentración plasmática es una práctica frecuente. La relación entre la concentración plasmática máxima (Cmax) y la concentración inhibitoria mínima (Cmax/ CIM) es el parámetro que mejor predice la eficacia. Objetivo: Determinar los parámetros farmacocinéticos (FC) de gentamicina en recién nacidos (RN) de termino. Material y Métodos: Se incluyeron RN de término, sin enfermedad crítica, en tratamiento con gentamicina (4 mg/kg/24 h) en los que se realizó monitoreo de su concentración plasmática. Se determinaron: clearence de eliminación (Cl), vida media de eliminación (t½) y volumen de distribución (Vd). Se estimó la Cmax/CIM, considerando una CIM de 1 μg/mL para Escherichia coli. Resultados: Participaron 13 RN. La media de Cmax fue 8,19 μg/mL y de Cmin 0,73 μg/mL. La media de los parámetros farmacocinéticos fue: Cl 0,26 mL/h, Vd 0,54 L/kg, t½ 6,8 h. La razón Cmáx/CIM fue ≥ 8 en 6 de los 13 RN. Conclusiones: Los parámetros FC de gentamicina en RN de término, sin enfermedad crítica, son predecibles. La posología habitual no permitió obtener valores de Cmax/CIM > 8 en todos los casos. Es necesario revisar la necesidad de monitorizar su concentración plasmática en forma sistemática y la posología de gentamicina en este grupo de pacientes.

Evaluation of Efficacy, Safety and Tolerability of a Combination of Clobetasol, Neomycin and Miconazole Versus Betamethasone, Clotrimazole and Neomycin Versus Betamethasone, Gentamycin and Miconazole in Subjects with Eczematous Disorders Associated with underlying Tinea or Yeast Infections.

Lobate GM Neo, 15 mg is a triple drug combination of a steroid clobetasol with anti-fungal miconazole and antibacterial neomycin in treatment of Eczematous disorders associated with underlying Tinea or Yeast Infections. Aims and Objectives: The study was designed to evaluate the efficacy, safety and tolerability of a combinations of clobetasol, neomycin and miconazole (Group A) versus betamethasone, clotrimazole, neomycin (Group B) versus betamethasone, gentamicin, miconazole (Group C) in subjects with any type of eczematous disorder associated with underlying tinea or yeast infection. Materials and Methods: This was an open label, parallel group, randomized comparative study. The primary endpoint analyzed was improvement in clinical score from baseline at the end of day 7 and other primary endpoint like hyperpigmentation were analyzed by the visual analogue scale of 1 to 10 at the end of day 7. Results: Thirty-six subjects were randomized to three groups. The clinical score showed a significant reduction from baseline at the end of day 7 in all the groups, i.e. 82.9%, 81.3% and 85.6% in Group A, B and C respectively. However, the difference between the groups were not statistically significant. Mean hyper pigmentation score showed significant decrease of 82.9% in Group A, 81.6% in Group B and 92.2% in Group C from baseline at the end of day 7. Conclusion: The triple combination of antifungal, antibacterial and potent steroid was found to be efficacious, safe and tolerable in reducing signs and symptoms (scaling, inflammation, burning and itching) of eczematous disorder associated with underlying tinea/yeast infection.

Once versus individualized multiple daily dosing of aminoglycosides in critically ill patients

The purpose of this study was to evaluate the once daily dosing [ODD] program in critically ill Egyptian patients compared to individualized multiple daily dosing [MDD] in terms of clinical and bacteriological efficacy. In addition, the incidence of nephrotoxicity associated with both regimens in this specific group of patients was assessed. Fifty-two patients with suspected or confirmed bacterial infections admitted to the Critical Care Medicine Department, Kasr El-Aini-Cairo University Hospitals comprised the study population. The amikacin group [30 patients] was sub-divided into 14 patients receiving amikacin ODD [1 g i.v.] and 16 patients receiving amikacin in MDD [500 mg i.v./dose]. The gentamicin group [22 patients] was sub-divided into 10 patients receiving the drug ODD [240 mg i.v.] and 12 patients receiving gentamicin MDD [80 mg i.v./dose]. Amikacin or gentamicin serum levels were determined by the enzyme multiplied immunoassay technique using Emit 2000. MDD regimen was adjusted based on the individual pharmacokinetic parameters using the Sawchuk-Zaske method. There was no significant difference between the two dosing regimens with regard to clinical and antibacterial efficacy or incidence of nephrotoxicity of both gentamicin and amikacin groups. In the ODD regimen, duration of treatment had no effect on increasing incidence of nephrotoxicity unlike the individualized MDD regimen. No dose adjustments were needed in the once daily dosing regimen since trough concentrations have never been above toxic level. The study showed that the ODD regimen is preferred in critically ill patients to individualized MDD as shown by comparable efficacy, nephrotoxicity and lesser need for therapeutic drug monitoring and frequent dose adjustments required in the individualized MDD regimen

The Modified Static Spacers Using Antibiotic-Impregnated Cement Rod in Two-Stage Revision for Infected Total Knee Arthroplasty

The two-stage exchange arthroplasty (one- or two-stage) is believed to be the gold standard for the management of infections following total knee arthroplasty. We herein report a novel two-stage exchange arthroplasty technique using an antibiotic-impregnated cement intramedullary nail, which can be easily prepared during surgery using a straight thoracic tube and a Steinmann pin, and may provide additional stability to the knee to maintain normal mechanical axis. In addition, there is less pain between the period of prosthesis removal and subsequent reimplantation. Less soft tissue contracture, less scar adhesion, easy removal of the cement intramedullary nail, and successful infection control are the advantages of this technique.

Cimento ósseo com gentamicina no tratamento da infecção óssea: Estudo da eluição in vitro / Bone cement and gentamIcin in the treatment of bone infection: Background and in vitro study

OBJETIVO: Determinar as características de eluição da gentamicina. MÉTODO: 480mg de gentamicina foram adicionadas a 40g de cimento ósseo. Dez corpos de teste semelhantes foram produzidos e imersos individualmente em solução salina tamponada por 28 dias. Amostras dos dias 1, 2, 7, 14, 21 e 28 foram analisadas pelo método de imunofluorescência polarizada. RESULTADO: A maior parte da gentamicina foi liberada do cimento nas primeiras 24 horas. Uma queda gradual se deu do 2º ao 14º dia. No 28º dia, a maior parte das amostras não apresentava mais níveis detectáveis do antibiótico. CONCLUSÃO: A mistura liberou quantidades elevadas e em doses terapêuticas do antibiótico de forma previsível ate o décimo quarto dia.

OBJECTIVE: To determine the elution characteristics of the antibiotic (gentamicin) mixed with bone cement. METHODS: 480mg of gentamicin was added to 40g of bone cement. Ten specimens were immersed in buffered saline solution for 28 days. Samples of days 1, 2, 7, 14, 21 and 28 were analyzed by the fluorescence polarization immunoassay method. RESULTS: Most of the gentamicin was eluted from the cement in the first 24 hours. A gradual downslide occurred between days 2 and 14. By the 28th day, there was no trace of the antibiotic. CONCLUSION: The mixture released high amounts of the antibiotic in a predictable (therapeutic) manner during at least fourteen days.

Once-Daily Gentamicin Administration for Community-Associated Methicillin Resistant Staphylococcus aureus in an in vitro Pharmacodynamic Model: Preliminary Reports for the Advantages for Optimizing Pharmacodynamic Index

PURPOSE: Community-associated methicillin resistant Staphylococcus aureus (CA-MRSA) infections are increasing. Although gentamicin (GEN) is usually susceptible against CA-MRSA, GEN is rarely considered for treatment as monotherapy. We employed an in vitro pharmacodynamic model (IVPDM) to compare efficacies of GEN against CA-MRSA with two dosing regimens [thrice-daily (TD), once-daily (OD)]. MATERIALS AND METHODS: Using two strains of CA-MRSA, we adopted IVPDM comprised of two-compartments with a surface-to-volume ratio of 5.34 cm-1. GEN regimens were simulated with human pharmacokinetic data of TD and OD. Experiments were performed over 48 hours in triplicate for each strain and dosing regimen. RESULTS: MICs of GEN for YSSA1 and YSSA15 were 1 and 2 mg/L, respectively. In OD, indices of peak/MIC were > 8.6 at least, in contrast to or = 3-log10 reduction in CFU/mL was demonstrated prior to 4 hours in TD and OD, and continued until 8 hours for both strains. However, reductions in the colony counts at 24 and 48 hours were significantly larger for OD compared to TD in both strains (p < 0.001). During TD, resistance developed in YSSA1 and small colony variants (SCVs) were documented in YSSA15. No resistance or SCVs were observed during OD in both strains. CONCLUSION: TD and OD showed the same killing slopes until 8 hours. After the 24 hours of experiments, OD of GEN would be advantageous not only in having more reductions in colony counts, but also suppressing the development of resistance or SCVs for 48 hours.

Ototoxicidade e otoproteção em orelha interna de cobaias utilizando gentamicina e amicacina: aspectos ultra-estruturais e funcionais / Ototoxicity and otoprotection in the inner ear of guinea pigs using gentamicin and amikacin: ultrastructural and functional aspects

A ototoxicidade ainda é um desafio para medicina. A descoberta dos mecanismos endógenos autoprotetores das células ciliadas externas associados a métodos de avaliação funcional e ultra-estrutural das mesmas abriu nova perspectiva no entendimento e controle destes mecanismos. OBJETIVO: O trabalho objetivou determinar se subdoses de gentamicina protegia contra ototoxicidade da amicacina baseado nestes mecanismos e determinar se a amplitude das emissões otoacústicas teria correlação com grau de integridade das células ciliadas. MATERIAL E MÉTODO: Estudo experimental. Utilizando 31 cobaias, administrou-se soro fisiológico, gentamicina e amicacina, isoladamente e associadas, via intramuscular, por 12, 30 e 42 dias. Pesquisa de emissões otoacústicas foi realizada no início e final do experimento, comparado com estudo da integridade coclear, por microscopia eletrônica. RESULTADOS: Subdoses de gentamicina não protegeram a orelha interna contra toxicidade da amicacina; diminuições da amplitude das emissões otoacústicas apresentaram forte correlação com aumento de lesões das células ciliadas. CONCLUSÃO: Os achados contribuem para o entendimento dos mecanismos de ototoxicidade e otoproteção da orelha interna. A determinação da correlação entre amplitude de emissões e integridade celular tem grande importância no acompanhamento das lesões de células ciliadas, com possível aplicação no monitoramento de ototoxicidade por drogas em humanos.

Ototoxicity is still a challenge to medicine. The discovery of self-protecting endogenous mechanisms of the outer hair cells associated with their functional and ultra-structural assessment methods has opened new horizons in the understanding and controlling of these mechanisms. AIM: this paper aimed at establishing whether or not underdoses of gentamicin could protect the inner ear against the harmful effects of amikacin, based on these protection mechanisms and determine if the otoacoustic emission amplitudes could be associated with the level of hair cell integrity. MATERIALS AND METHODS: Experimental study. We used 31 guinea pigs. They were injected with saline solution, gentamicin and amikacin, alone and in combinations -intramuscular injections - during 12, 30 and 42 days. The otoacoustic emissions were recorded in the beginning and at the end of the experiment, comparing it with the cochlear integrity study carried out by electron microscopy. RESULTS: gentamicin underdoses did not protect the inner ear against amikacin toxicity; the reduction in otoacoustic emissions was strongly associated with an increase in hair cell lesions. CONCLUSION: these findings help understand inner ear otoprotection and ototoxicity. Establishing the correlation between the emissions amplitude an cell integrity plays an important role in the follow up of hair cell damage, with possible monitoring of ototoxicity caused by drugs in humans.

Extended-spectrum beta-lactamase [ESBL] in Omani Children: Study of prevalence, risk factors and clinical outcomes at Sultan Qaboos University Hospital, Sultanate of Oman

Antimicrobial resistance is a growing problem worldwide, which imposes difficulties in the selection of appropriate empirical antimicrobial therapy. This study evaluated extended-spectrum ?-lactamase [ESBL] isolates in 2005 in The Department of Child Health at Sultan Qaboos University Hospital [SQUH], Oman. During the 12 month period from January 2005 to December 2005, ESBL isolates from paediatrics inpatients were identified and analysed. Risk factors for the patients who grew ESBLs were analysed. 13.3% of E. coli and 16.6% of Klebsiella pneumoniae isolated were ESBL producers. Most of the ESBLs were from urine [46.2%] and blood [42.6%]. The main risk factors for ESBL in these children were previous exposure to antimicrobials [100%], prolonged hospital stay, severe illness [92.3%] and female gender [84.6%]. Sensitivity of 100% was observed to carbapenems whereas 92% of the isolates were susceptible to amikacin. The oximino-cephalosporins were 100% resistant. Klebsiella pneumoniae were 100% resistant to piperacillin-tazobactam and nitrofurantoin. E. coli was 100% resistant to trimethoprim-sulfamethoxazole and ciprofloxacin. No resistance was recorded for the following combinations: amikacin plus piperacillin-tazobactam, amikacin plus nitrofurantoin and gentamicin plus nitrofurantoin. ESBL-producing organisms are becoming a major problem in Omani children. Exposure to antimicrobials and long admissions are modifiable risk factors that should be targeted for better control. Carbapenems are the most sensitive and reliable treatment options for infections caused by ESBLs. Amikacin plus piperacillin-tazobactam or nitrofurantoin are good alternatives

Efficacy and safety of gentamicin by interval and intravenous dosage adjustment based on the gestational age in Thai neonates.

OBJECTIVE: To determine the pharmacological efficacy and safety of the gentamicin regimen that adjusts intravenous dose and interval based on the gestational age (GA) in Thai neonates. MATERIAL AND METHOD: Neonates aged < or = 7 days, who had received gentamicin for clinically suspected or high risk of sepsis and had no contraindication to gentamicin usage were enrolled. They were stratified into four groups by GA as < or = 29, 30-33, 34-37 and > or = 38 weeks gestation. Gentamicin administration in each group was 5, 4.5, 4 and 4 mg/kg/dose every 48, 36, 36 and 24 hours respectively according to Neofax regimen. Peak serum gentamicin concentration (SGC), trough SGC and serum creatinine (Cr) were obtained. RESULTS: Forty-nine neonates were enrolled. Forty-four (89.7%) had peak SGC within the desirable range (5-12 mg/L). Three neonates had slightly high peak SGC. Their peak SGCs were 13.0, 12.21 and 12.20 mg/L. Two neonates had slightly low peak SGC. Their peak SGCs were 4.91 and 4.4 mg/L. All neonates had trough SGC below 2 mg/L. None had significant rising of serum Cr during the present study period. CONCLUSION: This gentamicin regimen yielded good pharmacological efficacy and safety in Thai neonates, who were in the first week of life and had no renal function impairment.

Tonometria, paquimetria e comprimento axial ocular em cães glaucomatosos submetidos à ablação uveal intravítrea / Tonometry, pachymetry and globe axial lenght in glaucomatous dogs submitted to intravitreal uveal ablation

Estudaram-se as alterações tonométricas, paquimétricas e de comprimento axial em cães com glaucoma submetidos à ablação uveal intravítrea. Foram avaliados 13 olhos irreversivelmente cegos de cães que apresentavam glaucoma crônico unilateral, nos quais realizou-se a ablação uveal intra-vítrea, por meio de injeção na câmara vítrea de 0,5ml de sulfato de gentamicina (40mg/ml) associado a 0,3ml de fosfato de dexametasona (4mg/ml). As mensurações da pressão intra-ocular (Po), espessura corneana e eixo axial com tonometria de aplanação, paquimetria ultra-sônica e ultra-sonografias modos A e B foram realizadas no dia da ablação (M0) e após uma (M1), quatro (M4), oito (M8), 12 (M12), 24 (M24) e 48 semanas (M48). A Po diminuiu significativamente em todos os momentos em relação ao M0, com aumento da espessura corneana ao longo do experimento. Nas avaliações ultra-sonográficas notou-se diminuição significativa do bulbo ocular a partir de M4, com medidas ultra-sonográficas modo A significativamente maiores que as do modo B. O procedimento foi efetivo na redução da Po e na diminuição do eixo axial, demonstrando ser viável no controle do glaucoma crônico em olhos irreversivelmente cegos, e ser uma alternativa à enucleação e inserção de prótese ocular

Changes in tonometry, pachymetry and globe axial length in glaucomatous dogs submitted to intravitreal uveal ablation were studied. Thirteen irreversible blind canine eyes were evaluated. They presented unilateral chronic glaucoma, in which intravitreal uveal ablation was performed, through vitreous chamber injection of 0.5ml of gentamicin sulfate solution (40mg/ml) with 0.3ml of dexametazon dissodic phosphate (4mg/ml). The measurements of intraocular pressure (IOP), corneal thickness and globe axial length with aplanation tonometry, ultrasound pachymetry and A and B-mode ultrasound scan were made on the day of the procedure (M0), and on the next day (M1), four (M4), eight (M8), 12 (M12), 24 (M24) and 48 weeks (M48) after. The IOP decreased on all moments in relation to M0, with corneal thickness increasing throughout the experiment. The ultrasonographic evaluations revealed significant globe decrease from M4, with A-scan measurements significantly higher than B-scan. The procedure was effective on intraocular pressure reduction and in shortening the axial length, showing to be feasible to control chronic glaucoma in irreversible blind eyes, as well as an alternative to enucleation and intraocular prothesis