Neurologic complications are relatively common after solid organ transplantation and affect 15%-30%of liver transplant recipients.Etiology is often related to immunosuppressant neurotoxicity and opportunistic infectio...Neurologic complications are relatively common after solid organ transplantation and affect 15%-30%of liver transplant recipients.Etiology is often related to immunosuppressant neurotoxicity and opportunistic infections.Most common complications include seizures and encephalopathy,and occurrence of central pontine myelinolysis is relatively specific for liver transplant recipients.Delayed allograft function may precipitate hepatic encephalopathy and neurotoxicity of calcineurin inhibitors typically manifests with tremor,headaches and encephalopathy.Reduction of neurotoxic immunosuppressants or conversion to an alternative medication usually result in clinical improvement.Standard preventive and diagnostic protocols have helped to reduce the prevalence of opportunistic central nervous system(CNS)infections,but viral and fungal CNS infections still affect 1%of liver transplant recipients,and the morbidity and mortality in the affected patients remain fairly high.Critical illness myopathy may also affect up to 7%of liver transplant recipients.Liver insufficiency is also associated with various neurologic disorders which may improve or resolve after successful liver transplantation.Accurate diagnosis and timely intervention are essential to improve outcomes,while advances in clinical management and extended post-transplant survival are increasingly shifting the focus to chronic post-transplant complications which are often encountered in a community hospital and an outpatient setting.展开更多
Background: The prevalence of head and neck cancers in the world is around 57% and predominantly occurs in Asian countries. It accounts for 30% of all cancers in India. The cure rate of locally advanced squamous cell ...Background: The prevalence of head and neck cancers in the world is around 57% and predominantly occurs in Asian countries. It accounts for 30% of all cancers in India. The cure rate of locally advanced squamous cell carcinoma of the head and neck (SCCHN) has only 30% - 60% even after combined therapeutic approaches. Epidermal Growth Factor Receptor (EGFR) antagonists are the most researched targets in the management of head and neck cancers. Claims at superior tumor control and additional survival benefit without any added toxicity make it an attractive option. With this case series we intend to see how nimotuzumab, a humanized monoclonal antibody, fares in difficult cases of head and neck cancers. Case Description: In this case series, total six patients of locally advanced cancer of head and neck region were treated weekly using cisplatin and nimotuzumab concurrently with radiation therapy (RT) for 6 - 7 weeks. Depending upon the disease stage as well as the general condition of the patient, different dose cycles and radiation doses were tailored. Patients were monitored for regular physical examinations and hematological tests followed by pre and post treatment computed tomography (CT) scans, Fludeoxyglucose positive emission tomography (FDG PET-CT) scans, and histopathology. All patients were assessed for toxicities and managed consequently. After completion of radiation and follow-up, 6 weeks later post treatment CT scans were carried out. Conclusion: This case series shows that combination of chemoradiation with nimotuzumab achieved good response rates with no evidence of residual disease/disease progression on follow-up. The patients’ tolerability with combination therapy was good and toxicity was acceptable. Nimotuzumab was found beneficial in combination with chemoradiation for locally advanced head and neck cancers.展开更多
Cancer is a systemic disease. In order to fully understand it, we must take a holistic view on how cancer interacts with its host. The brain monitors and responds to natural and aberrant signals arriving from the peri...Cancer is a systemic disease. In order to fully understand it, we must take a holistic view on how cancer interacts with its host. The brain monitors and responds to natural and aberrant signals arriving from the periphery, particularly those of metabolic or immune origin. As has been well described, a hallmark of cancer is marked disruption of metabolic and inflammatory processes. Depending on the salience and timing of these inputs, the brain responds via neural and humoral routes to alter whole-body physiology. These responses have consequences for tumor growth and metastasis, directly influencing patient quality of life and subsequent mortality. Additionally, environmental inputs such as light, diet, and stress, can promote inappropriate neural activity that benefits cancer. Here, I discuss evidence for brain-tumor interactions, with special emphasis on subcortical neuromodulator neural populations, and potential ways of harnessing this cross-talk as a novel approach for cancer treatment.展开更多
Background: Inhibition of CD4 T cells reduces stroke-induced infarction by inhibiting neuroinflammation in the ischemic brain in experimental stroke. Nevertheless, little is known about its effects on neuronal surviva...Background: Inhibition of CD4 T cells reduces stroke-induced infarction by inhibiting neuroinflammation in the ischemic brain in experimental stroke. Nevertheless, little is known about its effects on neuronal survival signaling pathways. In this study, we investigated the effects of CD4 T cell deficits on oxidative stress and on the Akt/mTOR cell signaling pathways after ischemic stroke in mice. Methods: MHC II gene knockout C57/BL6 mice, with significantly decreased CD4 T cells, were used. Stroke was induced by 60-min middle cerebral artery (MCA) occlusion. Ischemic brain tissues were harvested for Western blotting. Results: The impairment of CD4 T cell production resulted in smaller infarction. The Western blot results showed that iNOS protein levels robustly increased at 5 h and 24 h and then returned toward baseline at 48 h in wild-type mice after stroke, and gene KO inhibited iNOS at 5 h and 24 h. In contrast, the anti-inflammatory marker, arginase I, was found increased after stroke in WT mice, which was further enhanced in the KO mice. In addition, stroke resulted in increased phosphorylated PTEN, Akt, PRAS40, P70S6, and S6 protein levels in WT mice, which were further enhanced in the animals whose CD4 T cells were impaired. Conclusion: The impairment of CD4 T cell products prevents ischemic brain injury, inhibits inflammatory signals, and enhances the Akt/mTOR cell survival signaling pathways.展开更多
Finding and retaining the fight people has long been one of the keys to a company＇s success. As the market regains momentum after last year＇s crisis, many companies in China are again finding it increasingly hard to...Finding and retaining the fight people has long been one of the keys to a company＇s success. As the market regains momentum after last year＇s crisis, many companies in China are again finding it increasingly hard to meet staffing needs, making employer branding an opportunity area for most companies in their marketing and corporate practices展开更多
文摘Neurologic complications are relatively common after solid organ transplantation and affect 15%-30%of liver transplant recipients.Etiology is often related to immunosuppressant neurotoxicity and opportunistic infections.Most common complications include seizures and encephalopathy,and occurrence of central pontine myelinolysis is relatively specific for liver transplant recipients.Delayed allograft function may precipitate hepatic encephalopathy and neurotoxicity of calcineurin inhibitors typically manifests with tremor,headaches and encephalopathy.Reduction of neurotoxic immunosuppressants or conversion to an alternative medication usually result in clinical improvement.Standard preventive and diagnostic protocols have helped to reduce the prevalence of opportunistic central nervous system(CNS)infections,but viral and fungal CNS infections still affect 1%of liver transplant recipients,and the morbidity and mortality in the affected patients remain fairly high.Critical illness myopathy may also affect up to 7%of liver transplant recipients.Liver insufficiency is also associated with various neurologic disorders which may improve or resolve after successful liver transplantation.Accurate diagnosis and timely intervention are essential to improve outcomes,while advances in clinical management and extended post-transplant survival are increasingly shifting the focus to chronic post-transplant complications which are often encountered in a community hospital and an outpatient setting.
文摘Background: The prevalence of head and neck cancers in the world is around 57% and predominantly occurs in Asian countries. It accounts for 30% of all cancers in India. The cure rate of locally advanced squamous cell carcinoma of the head and neck (SCCHN) has only 30% - 60% even after combined therapeutic approaches. Epidermal Growth Factor Receptor (EGFR) antagonists are the most researched targets in the management of head and neck cancers. Claims at superior tumor control and additional survival benefit without any added toxicity make it an attractive option. With this case series we intend to see how nimotuzumab, a humanized monoclonal antibody, fares in difficult cases of head and neck cancers. Case Description: In this case series, total six patients of locally advanced cancer of head and neck region were treated weekly using cisplatin and nimotuzumab concurrently with radiation therapy (RT) for 6 - 7 weeks. Depending upon the disease stage as well as the general condition of the patient, different dose cycles and radiation doses were tailored. Patients were monitored for regular physical examinations and hematological tests followed by pre and post treatment computed tomography (CT) scans, Fludeoxyglucose positive emission tomography (FDG PET-CT) scans, and histopathology. All patients were assessed for toxicities and managed consequently. After completion of radiation and follow-up, 6 weeks later post treatment CT scans were carried out. Conclusion: This case series shows that combination of chemoradiation with nimotuzumab achieved good response rates with no evidence of residual disease/disease progression on follow-up. The patients’ tolerability with combination therapy was good and toxicity was acceptable. Nimotuzumab was found beneficial in combination with chemoradiation for locally advanced head and neck cancers.
基金This study was supported by NIMH BRAIN Initiative (F32 MH115431)
文摘Cancer is a systemic disease. In order to fully understand it, we must take a holistic view on how cancer interacts with its host. The brain monitors and responds to natural and aberrant signals arriving from the periphery, particularly those of metabolic or immune origin. As has been well described, a hallmark of cancer is marked disruption of metabolic and inflammatory processes. Depending on the salience and timing of these inputs, the brain responds via neural and humoral routes to alter whole-body physiology. These responses have consequences for tumor growth and metastasis, directly influencing patient quality of life and subsequent mortality. Additionally, environmental inputs such as light, diet, and stress, can promote inappropriate neural activity that benefits cancer. Here, I discuss evidence for brain-tumor interactions, with special emphasis on subcortical neuromodulator neural populations, and potential ways of harnessing this cross-talk as a novel approach for cancer treatment.
文摘Background: Inhibition of CD4 T cells reduces stroke-induced infarction by inhibiting neuroinflammation in the ischemic brain in experimental stroke. Nevertheless, little is known about its effects on neuronal survival signaling pathways. In this study, we investigated the effects of CD4 T cell deficits on oxidative stress and on the Akt/mTOR cell signaling pathways after ischemic stroke in mice. Methods: MHC II gene knockout C57/BL6 mice, with significantly decreased CD4 T cells, were used. Stroke was induced by 60-min middle cerebral artery (MCA) occlusion. Ischemic brain tissues were harvested for Western blotting. Results: The impairment of CD4 T cell production resulted in smaller infarction. The Western blot results showed that iNOS protein levels robustly increased at 5 h and 24 h and then returned toward baseline at 48 h in wild-type mice after stroke, and gene KO inhibited iNOS at 5 h and 24 h. In contrast, the anti-inflammatory marker, arginase I, was found increased after stroke in WT mice, which was further enhanced in the KO mice. In addition, stroke resulted in increased phosphorylated PTEN, Akt, PRAS40, P70S6, and S6 protein levels in WT mice, which were further enhanced in the animals whose CD4 T cells were impaired. Conclusion: The impairment of CD4 T cell products prevents ischemic brain injury, inhibits inflammatory signals, and enhances the Akt/mTOR cell survival signaling pathways.
文摘Finding and retaining the fight people has long been one of the keys to a company＇s success. As the market regains momentum after last year＇s crisis, many companies in China are again finding it increasingly hard to meet staffing needs, making employer branding an opportunity area for most companies in their marketing and corporate practices
