Afatinib is an oral tyrosine kinase inhibitor(TKI) approved for treating advanced non-small cell lung cancer. It is necessary to develop a simple quantification method for TKIs in order to facilitate therapeutic drug ...Afatinib is an oral tyrosine kinase inhibitor(TKI) approved for treating advanced non-small cell lung cancer. It is necessary to develop a simple quantification method for TKIs in order to facilitate therapeutic drug monitoring(TDM) in clinical settings. This study sought to develop a simple and sensitive competitive enzyme-linked immunosorbent assay(ELISA) to quantify afatinib in plasma for routine pharmacokinetic applications. An anti-afatinib antibody was obtained using(S)-N-4-(3-chloro-4-fluorophenyl)-7-(tetrahydrofuran-3-yloxy)-quinazoline-4,6-diamine(CTQD), which has the same substructure as afatinib, as a hapten. Enzyme labeling of afatinib with horseradish peroxidase was similarly performed using CTQD. A simple competitive ELISA for afatinib was developed based on the principle of direct competition between afatinib and the enzyme marker for the anti-afatinib antibody, which had been immobilized on the plastic surface of a microtiter plate. Plasma afatinib concentrations below the limit of quantification of 30 pg/mL were reproducibly measurable. Also, the values of plasma afatinib levels measured from 20 patients were comparable with those measured by high-performance liquid chromatography, and there was a strong correlation between the values determined by both methods(Y=0.976 X – 0.207, r=0.975). As indicated by its specificity and sensitivity, this newly developed ELISA for afatinib is an important tool for TDM and studies of the pharmacokinetics of afatinib.展开更多
We analyzed the relationship between the clinical characteristics, comorbidity, average relative dose intensity (aRDI) and outcome in patients of over 75 years old with malignant lymphoma. Of the 98 patients studied, ...We analyzed the relationship between the clinical characteristics, comorbidity, average relative dose intensity (aRDI) and outcome in patients of over 75 years old with malignant lymphoma. Of the 98 patients studied, the mean age was 79.9 years, and 68 patients (69.4%) had B-cell lymphomas, corresponding to mainly diffuse large B-cell lymphoma. The 5-year overall survival rate was 32.2% in 97 malignant lymphoma patients. T/NK subtype, poor performance status (PS) and high-intermediate/high international prognostic index (IPI) were found to be predictive of significantly poorer overall survival, as is the case in young patients. Correlation between comorbidity index and survival rate was not observed. We also analyzed the aRDI of cyclophosphamide and pirarubicin for 64/97 patients. The proportion of patients receiving ≤84% of the planned DI during five cycles gradually increased. Most patients could not maintain aRDI ≥85%. However, overall survival was not significantly different between patients with aRDI ≥0.85 and those with aRDI ≤0.84. In conclusion, the prognoses of very elderly patients with malignant lymphoma were not so poor when they were appropriately treated with modification of the applied dose and the duration of chemotherapy according to their status.展开更多
Relapsing polychondritis is a rare cartilaginous inflammatory disease affecting the external ear, nose, peripheral joints and tracheobronchial tree. It is characterized by recurrent inflammation and degeneration of ca...Relapsing polychondritis is a rare cartilaginous inflammatory disease affecting the external ear, nose, peripheral joints and tracheobronchial tree. It is characterized by recurrent inflammation and degeneration of cartilage and connective tissue. A 72-year-old man complained of dyspnea, cough and wheezing for 2 months. Diffuse wall thickening and narrowing from the trachea to segmental bronchus were seen on chest CT. Tracheostomy was performed in order to avoid as-phyxia, and he was diagnosed as relapsing polychondritis on the basis of pathology evaluation of a tracheal biopsy specimen. He was treated with high doses of a glucocorticoid, with which his symptoms improved. However, the cough and wheezing recurred after tapering of the glucocorticoid. His symptoms thereafter were improved by combination of the glucocorticoid with cyclosporine. The immunosuppressive agent provided effective treatment for glucocorticoid-resistant relapsing polychondritis.展开更多
Scurvy is now an almost forgotten disease, but it hasn’t yet disappeared entirely. Here, we report the case of a patient with scurvy who presented with multiple hemorrhages about 5 years after undergoing pharyngeal s...Scurvy is now an almost forgotten disease, but it hasn’t yet disappeared entirely. Here, we report the case of a patient with scurvy who presented with multiple hemorrhages about 5 years after undergoing pharyngeal surgery and radiochemotherapy for oropharyngeal cancer. This 60-year-old man was admitted to our hospital because of sudden onset of dyspnea and purpura. A physical examination and computed tomography revealed multifocal hemorrhages, namely, purpuras and petechiae on the legs and intramuscular and alveolar hemorrhages. Coagulation tests indicated a normal bleeding time and mild extension of the activated partial thromboplastin time. The coagulation factor activities were not low enough to account for such severe hemorrhages. No new hemorrhages were observed after admission. On questioning about his past eating habits, the patient reported having long had an extremely unbalanced diet, namely, a diet that was composed largely of carbohydrates with few fresh fruits and vegetables. This was due to the development of mechanical dysphagia after the operation. Since his vitamin C level was 0.5 μg/mL (normal range: 5.5 - 16.8 μg/mL), a diagnosis of scurvy was established. Thus, scurvy can still occur in modern times due to poor eating habits that arise from unusual settings. We must keep in mind that scurvy may be the cause when a patient presents with an apparently inexplicable tendency to hemorrhage.展开更多
文摘Afatinib is an oral tyrosine kinase inhibitor(TKI) approved for treating advanced non-small cell lung cancer. It is necessary to develop a simple quantification method for TKIs in order to facilitate therapeutic drug monitoring(TDM) in clinical settings. This study sought to develop a simple and sensitive competitive enzyme-linked immunosorbent assay(ELISA) to quantify afatinib in plasma for routine pharmacokinetic applications. An anti-afatinib antibody was obtained using(S)-N-4-(3-chloro-4-fluorophenyl)-7-(tetrahydrofuran-3-yloxy)-quinazoline-4,6-diamine(CTQD), which has the same substructure as afatinib, as a hapten. Enzyme labeling of afatinib with horseradish peroxidase was similarly performed using CTQD. A simple competitive ELISA for afatinib was developed based on the principle of direct competition between afatinib and the enzyme marker for the anti-afatinib antibody, which had been immobilized on the plastic surface of a microtiter plate. Plasma afatinib concentrations below the limit of quantification of 30 pg/mL were reproducibly measurable. Also, the values of plasma afatinib levels measured from 20 patients were comparable with those measured by high-performance liquid chromatography, and there was a strong correlation between the values determined by both methods(Y=0.976 X – 0.207, r=0.975). As indicated by its specificity and sensitivity, this newly developed ELISA for afatinib is an important tool for TDM and studies of the pharmacokinetics of afatinib.
文摘We analyzed the relationship between the clinical characteristics, comorbidity, average relative dose intensity (aRDI) and outcome in patients of over 75 years old with malignant lymphoma. Of the 98 patients studied, the mean age was 79.9 years, and 68 patients (69.4%) had B-cell lymphomas, corresponding to mainly diffuse large B-cell lymphoma. The 5-year overall survival rate was 32.2% in 97 malignant lymphoma patients. T/NK subtype, poor performance status (PS) and high-intermediate/high international prognostic index (IPI) were found to be predictive of significantly poorer overall survival, as is the case in young patients. Correlation between comorbidity index and survival rate was not observed. We also analyzed the aRDI of cyclophosphamide and pirarubicin for 64/97 patients. The proportion of patients receiving ≤84% of the planned DI during five cycles gradually increased. Most patients could not maintain aRDI ≥85%. However, overall survival was not significantly different between patients with aRDI ≥0.85 and those with aRDI ≤0.84. In conclusion, the prognoses of very elderly patients with malignant lymphoma were not so poor when they were appropriately treated with modification of the applied dose and the duration of chemotherapy according to their status.
文摘Relapsing polychondritis is a rare cartilaginous inflammatory disease affecting the external ear, nose, peripheral joints and tracheobronchial tree. It is characterized by recurrent inflammation and degeneration of cartilage and connective tissue. A 72-year-old man complained of dyspnea, cough and wheezing for 2 months. Diffuse wall thickening and narrowing from the trachea to segmental bronchus were seen on chest CT. Tracheostomy was performed in order to avoid as-phyxia, and he was diagnosed as relapsing polychondritis on the basis of pathology evaluation of a tracheal biopsy specimen. He was treated with high doses of a glucocorticoid, with which his symptoms improved. However, the cough and wheezing recurred after tapering of the glucocorticoid. His symptoms thereafter were improved by combination of the glucocorticoid with cyclosporine. The immunosuppressive agent provided effective treatment for glucocorticoid-resistant relapsing polychondritis.
文摘Scurvy is now an almost forgotten disease, but it hasn’t yet disappeared entirely. Here, we report the case of a patient with scurvy who presented with multiple hemorrhages about 5 years after undergoing pharyngeal surgery and radiochemotherapy for oropharyngeal cancer. This 60-year-old man was admitted to our hospital because of sudden onset of dyspnea and purpura. A physical examination and computed tomography revealed multifocal hemorrhages, namely, purpuras and petechiae on the legs and intramuscular and alveolar hemorrhages. Coagulation tests indicated a normal bleeding time and mild extension of the activated partial thromboplastin time. The coagulation factor activities were not low enough to account for such severe hemorrhages. No new hemorrhages were observed after admission. On questioning about his past eating habits, the patient reported having long had an extremely unbalanced diet, namely, a diet that was composed largely of carbohydrates with few fresh fruits and vegetables. This was due to the development of mechanical dysphagia after the operation. Since his vitamin C level was 0.5 μg/mL (normal range: 5.5 - 16.8 μg/mL), a diagnosis of scurvy was established. Thus, scurvy can still occur in modern times due to poor eating habits that arise from unusual settings. We must keep in mind that scurvy may be the cause when a patient presents with an apparently inexplicable tendency to hemorrhage.
