RESUMO
El estudio expone las acciones dirigidas a la reducción de los riesgos en el diseño de un nuevo proceso de producción del ingrediente farmacéutico activo de un inmunoterapéutico producido en el Centro de Ingeniería Genética y Biotecnología. El análisis modal de fallas y efectos fue conducido por un equipo multidisciplinario del referido centro. La administración de riesgos a la calidad se aplicó a la tecnología de obtención de una proteína recombinante con uso diagnóstico que se proponía transferir a la Dirección de Desarrollo Tecnológico. El riesgo en el diseño de un nuevo proceso de producción evaluó las fallas de mayor influencia en el bajo recobrado y el incumplimiento de las especificaciones de calidad del inmunoterapéutico. Las causas potenciales de estos fallas fueron: la insuficiente cantidad de viales de los bancos de células, el medio de cultivo complejo con componentes de origen bovino, la incorrecta manipulación de las muestras por los operarios, el uso de equipamiento no adecuado, los parámetros de operación (agitación, pH y conductividad) fuera de límites de especificación con efecto sobre la pureza por el alto porcentaje de contaminantes del hospedero; así como, un medio filtrante inadecuado unido a una incorrecta preparación del sistema de filtración redundantes en un producto no estéril. Las acciones llevaron a modificaciones en la tecnología propuesta por la Dirección de Investigaciones Biomédicas que permitió el diseño de un nuevo proceso productivo para un biofarmacéutico destinado al tratamiento de enfermedades virales crónicas(AU)
The study aimed at reducing risks in the design of a new production process for the active pharmaceutical ingredient of an immunotherapeutic produced at the Center for Genetic Engineering and Biotechnology. The failure mode and effects analysis were conducted by a multidisciplinary team from the center. Quality risk management was applied to the technology for obtaining a recombinant protein for diagnostic use that was proposed to be transferred to Technological Development Division. The risk analyses evaluated the greatest influence on low recovery and non-compliance with the immunotherapeutic quality specifications. The potential causes of the failures were: the insufficient number of vials in cell banks, the complex culture medium with components of bovine origin, the samples handling errors by the operators, the use of inappropriate equipment, the parameters of operation (agitation, pH and conductivity) outside specification limits affecting purity due to the high percentage of contaminants from the host; as well as, the inadequate filtering medium together with an incorrect preparation of the redundant filtration system in a non-sterile product. The actions could modify the technology proposed by Biomedical Research Division that allowed the design of a new production process of a biopharmaceutical product for the treatment of chronic viral diseases(AU)
Assuntos
Humanos , Masculino , Feminino , Gestão de Riscos/métodos , Viroses/tratamento farmacológico , Imunoterapia , Estágios do Ciclo de VidaRESUMO
Posttraumatic osteonecrosis of the femoral head (ONFH) affects patients at different ages and may lead to functional limitation and joint replacement, with total hip arthroplasty, which is a costly procedure. Proposed methods to optimize ischemic tissue regeneration have been reported. Phosphodiesterase-5 inhibitors act by inhibiting the degradation of guanosine 3',5'-cyclic monophosphate in the nitric oxide pathway, increasing its bioavailability and promoting vascular endothelial growth factor (VEGF)-mediated neovascular recruitment and the induction of tissue regeneration in the traumatized bone. Thirty male Sprague-Dawley rats (6 months old) were subjected to an experimental model of traumatic ONFH divided into two groups, according to the administration of 5 mg/kg sildenafil or water (control group). Rats were then killed at 7, 14, and 21 days. Histological (Goldner's trichrome), histochemical (periodic acid-Schiff [PAS]), and immunohistochemical (VEGF and osteopontin [OPN]) techniques were used to quantify bone and vascular responses. Higher levels of VEGF (p < 0.01) and OPN (p < 0.01) immunostaining in the epiphysis, the greater formation of osteoid tissue (p < 0.01 on Day 7; p < 0.05 on Day 14), and higher levels of PAS staining (p < 0.01 on Day 7) were observed in the sildenafil-treated group. The present study demonstrated that sildenafil optimized bone tissue regeneration by increasing VEGF signaling and OPN expression, with increased bone formation (osteoid and carbohydrate macromolecule deposition) in the early stages following traumatic ischemic insult. Thus, sildenafil treatment may improve the prognosis of patients with osteonecrosis.
Assuntos
Necrose da Cabeça do Fêmur , Cabeça do Fêmur , Animais , Regeneração Óssea , Nucleotídeo Cíclico Fosfodiesterase do Tipo 5 , Cabeça do Fêmur/patologia , Necrose da Cabeça do Fêmur/tratamento farmacológico , Necrose da Cabeça do Fêmur/patologia , Humanos , Isquemia , Masculino , Ratos , Ratos Sprague-Dawley , Citrato de Sildenafila/farmacologia , Citrato de Sildenafila/uso terapêutico , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
The use of cephalomedullary devices has gained popularity in the treatment of proximal femoral fractures. Despite their biomechanical advantages, several complications are well described in the literature. One of these complications, which is rarely reported, is the medial migration of the cephalic screw. The authors present this unusual complication in a case of a long-nail implant, which was treated with removal of the implants as a first step, and posterior osteosynthesis with a locked proximal femur plate as a second step, as well the outcome until fracture consolidation and resolution of the case.
RESUMO
Abstract The use of cephalomedullary devices has gained popularity in the treatment of proximal femoral fractures. Despite their biomechanical advantages, several complications are well described in the literature. One of these complications, which is rarely reported, is the medial migration of the cephalic screw. The authors present this unusual complication in a case of a long-nail implant, which was treated with removal of the implants as a first step, and posterior osteosynthesis with a locked proximal femur plate as a second step, as well the outcome until fracture consolidation and resolution of the case.
Resumo O uso dos dispositivos cefalomedulares tem ganhado popularidade no tratamento das fraturas do fêmur proximal. Apesar das vantagens biomecânicas, várias complicações são descritas, entre as quais a migração medial do parafuso cefálico é pouco conhecida. Os autores apresentam um caso dessa complicação incomum em um implante de haste longa tratada em dois tempos cirúrgicos para a retirada dos implantes e posterior osteossíntese com placa bloqueada para fêmur proximal, assim como o desfecho até a consolidação da fratura e resolução do caso.
Assuntos
Humanos , Feminino , Idoso , Próteses e Implantes , Equipamentos e Provisões , Fraturas do Fêmur , Fixação de Fratura , Fixação Interna de Fraturas , Fixação Intramedular de FraturasRESUMO
ABSTRACT Objective: To identify the patient profile that obtains better clinical and quality of life improvement after lumbar spinal stenosis surgery, comparing the results in the pre and postoperative periods. Methods: Thirty-seven patients with lumbar spine stenosis submitted to surgery were prospectively evaluated. Through the 36-Item Short Form General Health Survey (SF-36) questionnaire we performed a preoperative analysis to identify morbidities and social security benefit earning. The SF-36 is a subjective postoperative questionnaire to assess surgical success six months after the surgery. Results: There were unfavorable outcomes in patients who received social security benefits and in those who had morbidities. According to the SF-36 score, the surgical result is better when the patient is non-smoker (p=0.05), non-hypertense (p=0.040), non-diabetic (p =0.010) or non sedentary (p=0.019), respectively on mental health, pain, social aspects and general health domains. Conclusion: The patient profiles that best benefit from the surgery are those who do not have morbidities and had no social security benefit. Evidence Level II, Prospective Study.
RESUMO
OBJECTIVE: To identify the patient profile that obtains better clinical and quality of life improvement after lumbar spinal stenosis surgery, comparing the results in the pre and postoperative periods. METHODS: Thirty-seven patients with lumbar spine stenosis submitted to surgery were prospectively evaluated. Through the 36-Item Short Form General Health Survey (SF-36) questionnaire we performed a preoperative analysis to identify morbidities and social security benefit earning. The SF-36 is a subjective postoperative questionnaire to assess surgical success six months after the surgery. RESULTS: There were unfavorable outcomes in patients who received social security benefits and in those who had morbidities. According to the SF-36 score, the surgical result is better when the patient is non-smoker (p=0.05), non-hypertense (p=0.040), non-diabetic (p =0.010) or non sedentary (p=0.019), respectively on mental health, pain, social aspects and general health domains. CONCLUSION: The patient profiles that best benefit from the surgery are those who do not have morbidities and had no social security benefit. Evidence Level II, Prospective Study.
RESUMO
BACKGROUND: Significant symptomatic chronic aortic regurgitation (AR) leads to considerable left ventricular remodeling at the expense of myocyte hypertrophy and extracellular matrix remodeling. The relevance of interstitial fibrosis concentration in these patients is unknown. We analyzed the degree of fibrosis in the left ventricle (LV) in symptomatic patients with AR submitted to surgical treatment, and its relationship with functional and anatomical characteristics. OBJECTIVE: To evaluate myocardial fibrosis in chronic severe aortic regurgitation. METHODS: Twenty-eight patients with chronic symptomatic AR (16 with normal LV function and 12 with LV dysfunction) were selected and assessed pre- and postoperatively by echocardiography. Functional capacity was measured using maximal oxygen consumption (VO2max) through the cardiopulmonary test. Myocardial fibrosis volume fraction (MFV) was quantified through endomyocardial biopsy performed in all patients during surgery. We compared the histopathologic results with a nine-patient control group. RESULTS: The mean age was 39 +/- 12 years, 75% of the patients were male, and the rheumatic etiology accounted for 84% of the cases. Twenty-five patients remained in FC l and ll at the end of the study, and there was a significant reduction of the LV diameters between the preoperative and late postoperative timepoints. Three deaths occurred but they were not related to postoperative ventricular dysfunction. The parameters of the cardiopulmonary test were similar between pre- and postoperative timepoints. MFV in patients with AR was significantly higher than in the control group (3.47 +/- 1.9% vs 0.82 +/- 0.96%, respectively, p=0.001). There was no statistical correlation among LV fibrosis and LV diameters, LVEF and MVO2. CONCLUSION: In patients with significant symptomatic AR, the presence of limited myocardial fibrosis was not associated with clinical, echocardiographic or functional complications.
Assuntos
Insuficiência da Valva Aórtica/fisiopatologia , Fibrose Endomiocárdica/fisiopatologia , Remodelação Ventricular/fisiologia , Adulto , Insuficiência da Valva Aórtica/patologia , Insuficiência da Valva Aórtica/cirurgia , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Doença Crônica , Colágeno/metabolismo , Fibrose Endomiocárdica/etiologia , Fibrose Endomiocárdica/patologia , Feminino , Ventrículos do Coração/patologia , Humanos , Masculino , Consumo de Oxigênio/fisiologia , Cuidados Pós-Operatórios , Cuidados Pré-Operatórios , Volume Sistólico/fisiologiaRESUMO
FUNDAMENTO: A insuficiência aórtica crônica importante sintomática (IAo) leva a grande remodelamento ventricular esquerdo, à custa de hipertrofia de mióciotos e remodelamento da matriz extracelular. A relevância da concentração de fibrose intersticial nos pacientes acometidos é desconhecida. Analisamos o grau de fibrose no ventrículo esquerdo (VE) em pacientes sintomáticos com IAo submetidos a tratamento cirúrgico e sua relação com características funcionais e anatômicas. OBJETIVO: Avaliar a fibrose miocárdica na insuficiência aórtica crônica importante. MÉTODOS: Selecionaram-se 28 pacientes com IAo (16 com função VE normal e 12 com disfunção do VE), os quais foram analisados no pré e pós-operatório por ecodopplercardiografia. A capacidade funcional foi medida pelo teste de esforço cardiopulmonar. Para comparação dos resultados histopatológicos, um grupo-controle de 9 pacientes foi constituído. RESULTADOS: A média etária foi de 39 ± 12 anos, 75 por cento do sexo masculino com 84 por cento de etiologia reumática. Vinte e cinco pacientes permaneceram em classes funcionais I e II ao fim do estudo e apresentaram redução significativa dos diâmetros do VE entre os momentos pré e pós-operatórios. Houve três óbitos não relacionados à disfunção VE. Os parâmetros do teste cardiopulmonar não se modificaram entre o pré e o pós-operatório. O volume de fibrose intersticial em pacientes com IAo foi significativamente quando maior comparado ao grupo controle (3,47 ± 1,9 por cento vs 0,82 ± 0,96 por cento, respectivamente, p = 0,001). Não houve correlação entre o grau de fibrose do VE, parâmetros ecocardiográficos e funcionais. CONCLUSÃO: Em pacientes com IAo, a presença de fibrose miocárdica não se associou às alterações clínicas, ecocardiográficas ou funcionais.
BACKGROUND: Significant symptomatic chronic aortic regurgitation (AR) leads to considerable left ventricular remodeling at the expense of myocyte hypertrophy and extracellular matrix remodeling. The relevance of interstitial fibrosis concentration in these patients is unknown. We analyzed the degree of fibrosis in the left ventricle (LV) in symptomatic patients with AR submitted to surgical treatment, and its relationship with functional and anatomical characteristics. OBJECTIVE: To evaluate myocardical fibrosis in chronic severe aortic regurgitation. METHODS: Twenty-eight patients with chronic symptomatic AR (16 with normal LV function and 12 with LV dysfunction) were selected and assessed pre- and postoperatively by echocardiography. Functional capacity was measured using maximal oxygen consumption (VO2max) through the cardiopulmonary test. Myocardial fibrosis volume fraction (MFV) was quantified through endomyocardial biopsy performed in all patients during surgery. We compared the histopathologic results with a nine-patient control group. RESULTS: The mean age was 39 ± 12 years, 75 percent of the patients were male, and the rheumatic etiology accounted for 84 percent of the cases. Twenty-five patients remained in FC l and ll at the end of the study, and there was a significant reduction of the LV diameters between the preoperative and late postoperative timepoints. Three deaths occurred but they were not related to postoperative ventricular dysfunction. The parameters of the cardiopulmonary test were similar between pre- and postoperative timepoints. MFV in patients with AR was significantly higher than in the control group (3.47 ± 1.9 percent vs 0.82 ± 0.96 percent, respectively, p=0.001). There was no statistical correlation among LV fibrosis and LV diameters, LVEF and MVO2. CONCLUSION: In patients with significant symptomatic AR, the presence of limited myocardial fibrosis was not associated with clinical, echocardiographic or...
FUNDAMENTO: La insuficiencia aórtica crónica severa sintomática (IAo crónica severa) ocasiona una gran remodelación ventricular izquierda, por cuenta de hipertrofia de miociotos y remodelación de la matriz extracelular. Se desconoce la relevancia de la concentración de fibrosis intersticial en los pacientes acometidos. Analizamos el grado de fibrosis en el ventrículo izquierdo (VI) en pacientes sintomáticos con IAo crónica severa sometidos a tratamiento quirúrgico y su relación con características funcionales y anatómicas. OBJETIVO: Evaluar la fibrosis miocárdica en la insuficiencia aórtica crónica severa. MÉTODOS: Se seleccionaron a 28 pacientes con IAo crónica severa (16 con función VI normal y 12 con disfunción del VI), los que se analizaron en el pre y el postoperatorio por ecocardiografía Doppler. Se midió la capacidad funcional por la prueba de esfuerzo cardiopulmonar. Para comparación de los resultados histopatológicos, se constituyó a un Grupo Control de 9 pacientes. RESULTADOS: El promedio de edad fue de 39±12 años, el 75 por ciento del sexo masculino con el 84 por ciento de etiología reumática. El total de 25 pacientes permanecieron en clases funcionales I e II al fin del estudio y presentaron reducción significativa de los diámetros del VI entre los momentos pre y postoperatorios. Hubo tres óbitos no relacionados a la disfunción VI. Los parámetros de la prueba cardiopulmonar no se modificaron entre el pre y el postoperatorio. El volumen de fibrosis intersticial en pacientes con IAo crónica severa fue significativo cuando mayor, comparado al Grupo control (3,47 ± 1,9 por ciento vs. 0,82 ±0,96 por ciento, respectivamente, p = 0,001). No hubo correlación entre el grado de fibrosis del VI, parámetros ecocardiográficos y funcionales. CONCLUSIÓN: En pacientes con IAo crónica severa, la presencia de fibrosis miocárdica no se asoció a las alteraciones clínicas, ecocardiográficas o funcionales.
Assuntos
Adulto , Feminino , Humanos , Masculino , Insuficiência da Valva Aórtica/fisiopatologia , Fibrose Endomiocárdica/fisiopatologia , Remodelação Ventricular/fisiologia , Insuficiência da Valva Aórtica/patologia , Insuficiência da Valva Aórtica/cirurgia , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Doença Crônica , Colágeno/metabolismo , Fibrose Endomiocárdica/etiologia , Fibrose Endomiocárdica/patologia , Ventrículos do Coração/patologia , Consumo de Oxigênio/fisiologia , Cuidados Pós-Operatórios , Cuidados Pré-Operatórios , Volume Sistólico/fisiologiaRESUMO
Objetivo: Avaliar o comportamento biológico da membrana amniótica, através de análise histológica, após implantação como enxerto do tendão calcaneano de coelhos. Métodos: Foi produzida uma lesão cirúrgica completa, com ressecção de 2cm do tendão calcaneano, na pata traseira direita de 60 coelhos machos jovens. A lesão foi tratada com enxerto de membrana amniótica humana em 30 animais (grupo A) e nos 30 restantes (grupo B) serviu como controle. A resolução da lesão foi acompanhada por seis, oito e 12 semanas, após o que os animais foram sacrificados e as peças submetidas a análise macroscópica e microscópica (técnicas histológicas, histoquímicas e imunomarcação). Na análise microscópica foi observado que, com o tempo de resolução, o colágeno, de início desorganizado, se reorganizou, a reação inflamatória desapareceu, embora em um animal do subgrupo de 12 semanas notou-se o aparecimento de células gigantes de corpo estranho e, em alguns animais com oito semanas, ocorreu uma reação alérgica representada pelo grande número de mastócitos na área tendão-membrana. Não houve a participação de miofibroblastos no processo de remodelação, demonstrando que a vasculogênese foi adequada; com aumento temporário de proteoglicanas ácidas durante a etapa de fibrilogênese em áreas do tendão e pouca participação de fibras elásticas e glicoproteínas neutras durante o processo. Resultado: A membrana amniótica comportou-se como biocompatível diferenciando-se em tecido semelhante ao preexistente (tendinoso). Conclusão: A membrana amniótica humana, quando usada em experimento, em animais, mostrou-se eficiente como elemento reparador de lesões tendinosas...
Assuntos
Animais , Masculino , Coelhos , Âmnio/transplante , Tendão do Calcâneo/transplanteRESUMO
The authors report a tibial stress fracture in a 32 year-old man. His main complain was pain in the anteromedial portion of the knee. The clinical examination simulated a medial collateral ligament injury. The radiographic examination was normal. The MRI revealed a fracture of the anteromedial portion of the tibia. The need for MRI in selected cases is emphasized.