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PURPOSE: This article aims to comprehensively analyze the unique challenges in managing patients with metastatic Differentiated Thyroid Cancer (DTC) that develop radioiodine-refractory disease, especially in developing countries in Latin America. We discuss key contentious aspects of their treatment, such as the optimal timing for initiating systemic therapy, the choice of first-line medications, the appropriate timing for requesting molecular interrogation, and the challenges associated with accessing these drugs and molecular panels. METHODS: To illustrate these challenges and enhance understanding, we present five real clinical cases from the authors' experiences. RESULTS: Patients with Differentiated Thyroid Cancer (DTC) generally have an excellent prognosis, with an overall 10-year survival rate exceeding 97%. However, approximately 5% of DTC patients, especially those with distant metastases, may develop radioiodine-refractory disease, reducing survival rates. Access to medications remains difficult and time-consuming, particularly for patients within the public healthcare system. Urgent discussions on drug pricing involving all stakeholders are imperative. To break free from complacency, stakeholders must prioritize patient well-being by advocating for evidence-based drug pricing, increased participation in clinical trials, and streamlined regulatory processes. CONCLUSION: Beyond the recognized need for prospective randomized clinical trials to determine the optimal first-line drug and the timing of molecular testing, this type of manuscript plays a pivotal role in stimulating discussions and disseminating comprehensive knowledge about the challenges associated with treating and monitoring patients with radioiodine-refractory thyroid carcinoma, especially in developing countries.
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BACKGROUND: Envenomation caused by Bothrops alternatus is common in Southern Brazil. Acute Kidney Injury occurs after Bothrops snakebite and more information is necessaryrequired to understand its mechanism. OBJECTIVE: The objective was to evaluate the effect of Bothrops alternatus venom (BaV) on renal cells and rat isolated kidney function. METHODS: Wistar rats (n = 6, weighing 260-320 g) were perfused with a Krebs-Henseleit solution containing 6 g 100 mL-1 of bovine serum albumin. After 30 minutes, the kidneys were perfused with BaV to a final concentration of 1 and 3 µgmL-1; and subsequently were evaluated for Perfusion Pressure (PP), Renal Vascular Resistance (RVR), Urinary Flow (UF), Glomerular Filtration Rate (GFR), and percentage of electrolyte tubular transport. Renal histological analysis, cytokine release, oxidative stress and cytotoxicity in renal proximal tubular cells were assessed. RESULTS: BaV reduced PP, RVR, GFR, UF, total and proximal sodium transport (%TNa+), and chloride (%TCl-) in the isolated kidney perfusion model. Histological analysis of perfused kidneys disclosed the presence of proteinaceous material in the glomeruli and renal tubules, vacuolar tubular epithelial cell degeneration, Bowman's capsule degeneration, swelling of glomerular epithelial cells, glomerular atrophy and degeneration, and the presence of intratubular protein. Cytokine release (TNF-α, IL-1ß, IL-10) and oxidative stress were increased in the kidneys. The viability of LLC-MK2 cells (IC50: 221.3 µg/mL) was decreased by BaV and necrosis was involved in cell death. CONCLUSION: These findings indicate that BaV modifies functional parameters in an isolated perfused kidney model and has cytotoxic effects on renal lineage cells.
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Citocinas/biossíntese , Túbulos Renais/efeitos dos fármacos , Venenos de Serpentes/farmacologia , Animais , Bothrops , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Taxa de Filtração Glomerular , Túbulos Renais/metabolismo , Túbulos Renais/patologia , Macaca mulatta , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Relação Estrutura-AtividadeRESUMO
Bredemeyera floribunda roots are popularly used to treat snakebites in the semiarid region of Northeast Brazil, and previous studies indicate the anti-ophidian actions of triterpenoid saponins found in its roots. To assess B. floribunda root extract (BFRE) activity against the effects of Bothrops jararacussu venom (BjuV), antiphospholipasic, antiproteolytic, antihemorrhagic, antinecrotic, and anti-edematogenic activities were investigated in mice. Phytochemical analysis revealed the presence of saponins, flavonoids, and sugars, with rutin and saccharose being the major constituents of BFRE. Acute toxicity was determined and BFRE was nontoxic to mice. Phospholipase A2 and proteolytic activities induced by BjuV were inhibited in vitro by BFRE at all concentrations tested herein. BFRE (150 mg/kg) inhibited paw edema induced by BjuV (50 µg/animal), reducing total edema calculated by area under the curve, but carrageenan-induced paw edema was unchanged. Hemorrhagic and necrotizing actions of BjuV (50 µg/animal) were considerably decreased by BFRE treatment. Thus, BFRE blocked the toxic actions of B. jararacussu venom despite having no anti-inflammatory activity, which points to a direct inhibition of venom's toxins, as demonstrated in the in vitro assays. The larger amounts of rutin found in BFRE may play a role in this inhibition, since 3′,4′-OH flavonoids are known inhibitors of phospholipases A2.
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Animais , Masculino , Ratos , Antivenenos/farmacologia , Extratos Vegetais/farmacologia , Raízes de Plantas/química , Venenos de Crotalídeos/antagonistas & inibidores , Edema/tratamento farmacológico , Hemorragia/etiologia , Antivenenos/isolamento & purificação , Bothrops , Venenos de Crotalídeos/toxicidade , Polygalaceae/química , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Edema/etiologia , Hemorragia/tratamento farmacológicoRESUMO
Bredemeyera floribunda roots are popularly used to treat snakebites in the semiarid region of Northeast Brazil, and previous studies indicate the anti-ophidian actions of triterpenoid saponins found in its roots. To assess B. floribunda root extract (BFRE) activity against the effects of Bothrops jararacussu venom (BjuV), antiphospholipasic, antiproteolytic, antihemorrhagic, antinecrotic, and anti-edematogenic activities were investigated in mice. Phytochemical analysis revealed the presence of saponins, flavonoids, and sugars, with rutin and saccharose being the major constituents of BFRE. Acute toxicity was determined and BFRE was nontoxic to mice. Phospholipase A2 and proteolytic activities induced by BjuV were inhibited in vitro by BFRE at all concentrations tested herein. BFRE (150 mg/kg) inhibited paw edema induced by BjuV (50 µg/animal), reducing total edema calculated by area under the curve, but carrageenan-induced paw edema was unchanged. Hemorrhagic and necrotizing actions of BjuV (50 µg/animal) were considerably decreased by BFRE treatment. Thus, BFRE blocked the toxic actions of B. jararacussu venom despite having no anti-inflammatory activity, which points to a direct inhibition of venom's toxins, as demonstrated in the in vitro assays. The larger amounts of rutin found in BFRE may play a role in this inhibition, since 3',4'-OH flavonoids are known inhibitors of phospholipases A2.
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Antivenenos/farmacologia , Venenos de Crotalídeos/antagonistas & inibidores , Edema/tratamento farmacológico , Hemorragia/etiologia , Extratos Vegetais/farmacologia , Raízes de Plantas/química , Polygalaceae/química , Animais , Antivenenos/isolamento & purificação , Bothrops , Venenos de Crotalídeos/toxicidade , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Edema/etiologia , Hemorragia/tratamento farmacológico , Masculino , RatosRESUMO
The aim of this study was to analyze the alterations of arm and leg movements of patients during stroke gait. Joint angles of upper and lower limbs and spatiotemporal variables were evaluated in two groups: hemiparetic group (HG, 14 hemiparetic men, 53 ± 10 years) and control group (CG, 7 able-bodied men, 50 ± 4 years). The statistical analysis was based on the following comparisons (P ≤ 0.05): 1) right versus left sides of CG; 2) affected (AF) versus unaffected (UF) sides of HG; 3) CG versus both the affected and unaffected sides of HG, and 4) an intracycle comparison of the kinematic continuous angular variables between HG and CG. This study showed that the affected upper limb motion in stroke gait was characterized by a decreased range of motion of the glenohumeral (HG: 6.3 ± 4.5, CG: 20.1 ± 8.2) and elbow joints (AF: 8.4 ± 4.4, UF: 15.6 ± 7.6) on the sagittal plane and elbow joint flexion throughout the cycle (AF: 68.2 ± 0.4, CG: 46.8 ± 2.7). The glenohumeral joint presented a higher abduction angle (AF: 14.2 ± 1.6, CG: 11.5 ± 4.0) and a lower external rotation throughout the cycle (AF: 4.6 ± 1.2, CG: 22.0 ± 3.0). The lower limbs showed typical alterations of the stroke gait patterns. Thus, the changes in upper and lower limb motion of stroke gait were identified. The description of upper limb motion in stroke gait is new and complements gait analysis.
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Adulto , Humanos , Masculino , Pessoa de Meia-Idade , Braço/fisiologia , Marcha/fisiologia , Perna (Membro)/fisiologia , Paresia/fisiopatologia , Acidente Vascular Cerebral/fisiopatologia , Pontos de Referência Anatômicos , Fenômenos Biomecânicos , Articulação do Cotovelo/fisiopatologia , Movimento/fisiologia , Amplitude de Movimento Articular , Estatísticas não Paramétricas , Articulação do Ombro/fisiopatologiaRESUMO
The aim of this study was to analyze the alterations of arm and leg movements of patients during stroke gait. Joint angles of upper and lower limbs and spatiotemporal variables were evaluated in two groups: hemiparetic group (HG, 14 hemiparetic men, 53 ± 10 years) and control group (CG, 7 able-bodied men, 50 ± 4 years). The statistical analysis was based on the following comparisons (P ≤ 0.05): 1) right versus left sides of CG; 2) affected (AF) versus unaffected (UF) sides of HG; 3) CG versus both the affected and unaffected sides of HG, and 4) an intracycle comparison of the kinematic continuous angular variables between HG and CG. This study showed that the affected upper limb motion in stroke gait was characterized by a decreased range of motion of the glenohumeral (HG: 6.3 ± 4.5, CG: 20.1 ± 8.2) and elbow joints (AF: 8.4 ± 4.4, UF: 15.6 ± 7.6) on the sagittal plane and elbow joint flexion throughout the cycle (AF: 68.2 ± 0.4, CG: 46.8 ± 2.7). The glenohumeral joint presented a higher abduction angle (AF: 14.2 ± 1.6, CG: 11.5 ± 4.0) and a lower external rotation throughout the cycle (AF: 4.6 ± 1.2, CG: 22.0 ± 3.0). The lower limbs showed typical alterations of the stroke gait patterns. Thus, the changes in upper and lower limb motion of stroke gait were identified. The description of upper limb motion in stroke gait is new and complements gait analysis.
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Braço/fisiologia , Marcha/fisiologia , Perna (Membro)/fisiologia , Paresia/fisiopatologia , Acidente Vascular Cerebral/fisiopatologia , Adulto , Pontos de Referência Anatômicos , Fenômenos Biomecânicos , Articulação do Cotovelo/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Movimento/fisiologia , Amplitude de Movimento Articular , Articulação do Ombro/fisiopatologia , Estatísticas não ParamétricasRESUMO
OBJETIVO: O estudo teve como objetivo determinar se há diferenças na distribuição de pressão plantar estática e dinâmica entre crianças obesas e eutróficas. MÉTODO: Foram avaliadas vinte crianças, divididas em dois grupos (grupo de obesos e grupo de eutróficos), com idades entre nove e onze anos. As avaliações incluíram medidas das variáveis de pressão plantar na postura ereta e na marcha por meio do sistema Pedar (Novel GMbH). RESULTADOS: Constatou-se que as crianças obesas apresentaram maiores áreas de contato, picos de pressão, pressões médias máximas e integrais pressão-tempo, quando comparadas às eutróficas, com diferenças significativas, principalmente nas regiões do médio-pé e antepé. CONCLUSÕES: As diferenças observadas entre os grupos indicam que crianças obesas podem apresentar modificações importantes nos pés em função da sobrecarga excessiva e repetitiva à qual estão expostas, aumentando o risco para o desenvolvimento de lesões e patologias nos pés. Portanto, é necessário que programas de intervenção sejam implantados a fim de interferir também na progressão de problemas de natureza estrutural e funcional relacionados à obesidade.
OBJECTIVE: The aim of this study was to determine whether there were differences in static and dynamic plantar pressure distribution between obese and non-obese children. METHOD: Twenty children aged from nine to eleven years were assessed and divided into two groups (obese and non-obese groups). The assessments included measurements of plantar pressure variables while standing and walking, by means of the Pedar System (Novel GMbH). RESULTS: The obese children presented greater contact area, peak pressure, maximum mean pressure and pressure-time integral, in comparison with the non-obese children, with significant differences particularly in the midfoot and forefoot areas. CONCLUSION: The differences observed between the groups indicated that obese children may present significant modifications to their feet because of the excessive and repetitive loads that they are exposed to, which increases the risk of developing foot injuries and pathologies. It is suggested that there is a need to implement intervention programs with the aim of interfering with the progression of obesity-related problems from a structural and functional perspective.
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CONTEXTUALIZAÇÃO: A articulação do joelho destaca-se por ser uma estrutura comumente afetada por alterações degenerativas, lesões e síndromes. Avaliações clínicas objetivas e precisas são necessárias para estabelecimento de diagnósticos adequados e, conseqüentemente, melhores resultados tanto das cirurgias como dos programas de reabilitação. OBJETIVO: Verificar a presença de diferença entre os joelhos durante a marcha e sua relação com a diferença estática, nos planos sagital e frontal. MÉTODO: Foram avaliados 45 sujeitos saudáveis, sendo 21 do sexo masculino e 24 do sexo feminino. Mediu-se a amplitude de movimento da articulação do joelho, na marcha, por meio da eletrogoniometria. A avaliação da postura estática do joelho foi feita por meio de fotogrametria. Os dados foram analisados descritivamente e aplicou-se o coeficiente de correlação de Pearson. RESULTADOS: Os indivíduos apresentaram valores médios similares para os lados direito e esquerdo (diferença de aproximadamente 0,5º) no registro estático dos planos sagital e frontal. No entanto, o desvio-padrão foi alto, indicando grande variabilidade entre os sujeitos. Para o registro dinâmico, a diferença entre os joelhos foi de 0,4º para o plano sagital e 1º para o plano frontal. No entanto, a variabilidade encontrada também foi alta, principalmente para o plano frontal. Não foi encontrada correlação entre os registros estáticos e dinâmicos nos dois planos de movimento avaliados (r= -0,003 e p= 0,492 para o plano sagital e r= -0,014 e p= 0,465 para o plano frontal). CONCLUSÕES: Embora não tenha sido encontrada relação entre os registros estático e dinâmico, esse assunto merece ser investigado em estudos futuros, avaliando-se grupos mais amplos e com alterações posturais específicas e mais pronunciadas.
INTRODUCTION: The knee joint stands out as a structure that is commonly affected by degenerative alterations, injuries and syndromes. Precise objective clinical evaluations are necessary for establishing appropriate diagnoses and, consequently, better results from both surgical procedures and rehabilitation programs. OBJECTIVE: To investigate the existence of differences between the knees during gait and their relationship with the static difference in the sagittal and frontal planes. METHOD: Forty-five healthy subjects were included, of whom 21 were male and 24 were female. Knee joint range of motion was measured during gait by means of flexible electrogoniometry. The static posture of the knee was evaluated by means of photogrammetry. The data were analyzed descriptively and the Pearson correlation coefficient was applied. RESULTS: The individuals presented mean values that were similar for right and left knees in static recordings of the sagittal and frontal planes (difference of approximately 0.5º). However, the standard deviation was large, thus indicating great variability between the subjects. For the dynamic recordings, the difference between the knees was 0.4º for the sagittal plane and 1º for the frontal plane. The variability found was also large, especially for the frontal plane. There was no correlation between the static and dynamic recordings in the two planes of motion evaluated (r = -0.003 and p = 0.492 for the sagittal plane; r = -0.014 and p = 0.465 for the frontal plane). CONCLUSION: Although no relationship was found between the static and dynamic recordings, this matter deserves investigation in future studies, with evaluations of broader groups with specific and more pronounced postural abnormalities.
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Humanos , Masculino , Feminino , Marcha , Articulação do Joelho , Extremidade Inferior , PosturaRESUMO
Thirteen patients with Schistosoma mansoni myelopathy are reported. Neurologic syndromes included acute areflexic flaccid paraplegia (three), thoracic myelopathy with hyperreflexia and Babinski sign (six), and a cauda equina syndrome (four). Inflammatory granulomas and a schistosome worm in a leptomeningeal vein of the spinal cord were observed in the one patient coming to necropsy.
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Esquistossomose mansoni/complicações , Doenças da Medula Espinal/etiologia , Adolescente , Adulto , Idoso , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Meninges/irrigação sanguínea , Meninges/parasitologia , Pessoa de Meia-Idade , Óvulo , Paraplegia/etiologia , Paraplegia/parasitologia , Paraplegia/patologia , Polirradiculopatia/etiologia , Polirradiculopatia/parasitologia , Polirradiculopatia/patologia , Reflexo Anormal , Esquistossomose mansoni/patologia , Doenças da Medula Espinal/parasitologia , Doenças da Medula Espinal/patologiaRESUMO
O movimento humano requer controle e coordenação simultâneos entre diversos segmentos corporais e, para tanto, o sistema motor elabora estratégias neuro-musculares e fiom de reduzir os graus de liberdade. Uma maneira de se investigar a flexibilidade e adaptabilidade do sistema motor e através do estudo biomecânico de padrões de movimentos submetidos a diferentes demandas ambientais. Assim, este estudo propõe-se a avaliar respostas eletromiográficas dos principais músculos locomotores, bem como a componente vertical da força reação do solo durante o andar no plano, subindo e descendo escadas em crianças. Através da análise do comportamento adaptativo destes parâmetros neuro-musculares e cinéticos, pode-se obter indicadores quantitativos e qualitativos da função coordenativa do sistema motor
Abstract - The human movement is dependent on the contrai of multiple coordinations and the motor system elaborates neuro-muscular strategies to reduce the degrees of freedom of multi-joint movements. A way to investigate the flexibility and adaptability characteristics of the motor system is through the biomechanical study of movement patterns submitted to different environmental constraints. The purpose of this study is to analyse the electromyographic activity of locomotor muscles and the vertical componente ofthe ground reaction force in children during levei and stair walking. Through the analysis of the adaptative behavior of these selected neuromuscular and kinetic parameters, it is possible to identify qualitative and quantitative indicators of the coordinative function ofthe human motor system
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Humanos , Criança , Atividade Motora , Adaptação Psicológica , Locomoção , Manifestações Neurológicas , Maleabilidade , Eletromiografia , Fenômenos BiomecânicosRESUMO
It is reported our diagnosis and therapeutical experience with a patient that presented clinical, radiological and tomographical manifestations of paracoccidioidomycosis with involvement of lungs, brain and spinal cord. Besides being a rare case the authors call attention for the extreme difficulty in defining the final diagnosis, which was achieved only after laminectomy and surgical biopsy of the intra spinal cord tumor at the C5 level. The patient received two series of treatment with ketoconazole (400-600 mg/day). After both the patient presented tonic and clonic convulsive disorders. We speculated about a possible perigranulomatous inflammatory response related to the therapeutical intervention, not yet described in literature.
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Doenças do Sistema Nervoso Central/diagnóstico , Paracoccidioidomicose/diagnóstico , Doenças do Sistema Nervoso Central/tratamento farmacológico , Humanos , Cetoconazol/uso terapêutico , Masculino , Pessoa de Meia-Idade , Paracoccidioidomicose/tratamento farmacológicoRESUMO
O presente relato de caso, descreve nossa experiência diagnóstica e terapêutica com um paciente que apresentou manifestaçöes clínicas, radiológicas e tomográficas de paracoccidioidomicose comprometendo os pulmöes, cérebro e, particularmente, a medula espinhal. Além da raridade do caso, chama-se a atençäo para a extrema dificuldade na elucidaçäo diagnóstica definitiva, obtida somente após laminectomia e biópisa cirúrgica de tumoraçäo iintramedular ao nvel de C5. O paciente recebeu duas séries de tratamento com ketoconazol (400 a 600 mg/dia). No início de ambas apresentou crise convulsiva tònico-clónica. Especula-se sobre uma possível resposta inflamatória perigranulomatosa intracerebral, relacionada à intervençäo terapêutica, ainda sem relato na literatura