The Experts below are selected from a list of 88719 Experts worldwide ranked by ideXlab platform
Shawn B. Bratton - One of the best experts on this subject based on the ideXlab platform.
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the apaf 1 procaspase 9 apoptosome complex functions as a proteolytic based molecular timer
The EMBO Journal, 2009Co-Authors: Srinivas Malladi, Howard O. Fearnhead, Madhavi Challamalladi, Shawn B. BrattonAbstract:During stress‐induced apoptosis, the initiator caspase‐9 is activated by the Apaf‐1 apoptosome and must remain bound to retain significant catalytic activity. Nevertheless, in apoptotic cells the vast majority of processed caspase‐9 is paradoxically observed outside the complex. We show herein that apoptosome‐mediated cleavage of procaspase‐9 occurs exclusively through a CARD‐displacement mechanism, so that unlike the effector procaspase‐3, procaspase‐9 cannot be processed by the apoptosome as a typical substrate. Indeed, procaspase‐9 possessed higher affinity for the apoptosome and could displace the processed caspase‐9 from the complex, thereby facilitating a Continuous Cycle of procaspase‐9 recruitment/activation, processing, and release from the complex. Owing to its rapid autocatalytic cleavage, however, procaspase‐9 per se contributed little to the activation of procaspase‐3. Thus, the Apaf‐1 apoptosome functions as a proteolytic‐based ‘molecular timer’, wherein the intracellular concentration of procaspase‐9 sets the overall duration of the timer, procaspase‐9 autoprocessing activates the timer, and the rate at which the processed caspase‐9 dissociates from the complex (and thus loses its capacity to activate procaspase‐3) dictates how fast the timer ‘ticks’ over.
Nauman Tariq - One of the best experts on this subject based on the ideXlab platform.
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short term oral methylergonovine maleate prophylaxis for status migrainosus case series and review of literature
Frontiers in Neurology, 2019Co-Authors: Najiya Haque, Nauman TariqAbstract:Background Intravenous dihydroergotamine (DHE) is frequently used during inpatient hospitalizations or outpatient infusion therapies for 3-5 days in order to break the Continuous Cycle of status migrainosus. Long term use of ergots can cause safety concerns especially fibrosis. We tried a short term 7 days prophylaxis of oral methylergonovine after discharge in order to prevent status migrainosus relapse and extend the therapeutic benefit from IV DHE. Methods Patients were diagnosed with status migrainosus in clinic setting based on the ICHD-III criteria. They received IV DHE for 3-5 days followed by methylergonovine maleate oral tablets as prophylaxis for 7 days post discharge. They were asked to maintain their headache diaries which included data on headache frequency and intensity. A post discharge follow up at 1 week and 6-8 weeks was planned. Clinical improvement was defined as > 50% decrease in frequency and intensity of headaches. Intensity was graded on verbal numerical rating scale (VNRS) with 10 being the worst possible pain. Results A total of 3 patients who benefited from IV DHE, consented to trial of Methylergonovine Maleate 0.4 mg oral tablets three times a day prophylaxis on the day of discharge for a period of 7 days. At 1 week post discharge, all of the 3 patients had reported sustained improvement with severity dropping from an average of 8/10 intensity to 3/10 on VNRS. The headaches frequency had dropped from daily to episodic in 2 of the 3 patients. At an average of 7 weeks post discharge, 2 out of the 3 patients had reported sustained benefit. The third patient relapsed to the pre-admission status migrainosus severity. One patient reported mild diarrhea and nausea but was still able to continue the drug for a week. Conclusion Oral methylergonovine maleate prophylaxis for 7 days after IV DHE is feasible and safe for status migrainosus. This approach has the potential to prolonged the benefit of IV DHE and prevent relapse in to status migrainosus.
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Short Term Oral Methylergonovine Maleate Prophylaxis for Status Migrainosus. Case Series and Review of Literature
Frontiers Media S.A., 2019Co-Authors: Najiya Haque, Nauman TariqAbstract:Background: Intravenous dihydroergotamine (DHE) is frequently used during inpatient hospitalizations or outpatient infusion therapies for 3–5 days in order to break the Continuous Cycle of status migrainosus. We tried a short term 7 days prophylaxis of oral methylergonovine after discharge in order to prevent status migrainosus relapse and extend the therapeutic benefit from IV DHE.Methods: Patients were diagnosed with status migrainosus in clinic setting based on the ICHD-III criteria. They received 1 mg IV DHE every 8 h along with metoclopramide for 3–5 days followed by methylergonovine maleate oral tablets as prophylaxis for 7 days post discharge. They were asked to maintain their headache diaries which included data on headache frequency and intensity. A post discharge follow up at 1 and 68 weeks was planned. Clinical improvement was defined as >50% decrease in frequency and intensity of headaches. Intensity was graded on verbal numerical rating scale (VNRS) with 10 being the worst possible pain. The institutes IRB and ethics committee exempted this study from review given that it had only 3 patients.Results: A total of 3 patients 25–45 years of age who benefited from IV DHE, consented to trial of Methylergonovine Maleate 0.4 mg oral tablets three times a day prophylaxis on the day of discharge for a period of 7 days. At 1 week post discharge, all of the 3 patients had reported sustained improvement with severity dropping from an average of 8/10 intensity to 3/10 on VNRS. The headaches frequency had dropped from daily to episodic in 2 of the 3 patients. At an average of 7 weeks post discharge, 2 out of the 3 patients had reported sustained benefit. The third patient relapsed to the pre-admission status migrainosus severity. One patient reported mild diarrhea and nausea but was still able to continue the drug for a week.Conclusion: Methylergonovine maleate after 3–5 days of IV DHE infusions may be a feasible treatment strategy for status migrainosus. This approach has the potential to prolonged the benefit of IV DHE and prevent relapse in to status migrainosus
Srinivas Malladi - One of the best experts on this subject based on the ideXlab platform.
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the apaf 1 procaspase 9 apoptosome complex functions as a proteolytic based molecular timer
The EMBO Journal, 2009Co-Authors: Srinivas Malladi, Howard O. Fearnhead, Madhavi Challamalladi, Shawn B. BrattonAbstract:During stress‐induced apoptosis, the initiator caspase‐9 is activated by the Apaf‐1 apoptosome and must remain bound to retain significant catalytic activity. Nevertheless, in apoptotic cells the vast majority of processed caspase‐9 is paradoxically observed outside the complex. We show herein that apoptosome‐mediated cleavage of procaspase‐9 occurs exclusively through a CARD‐displacement mechanism, so that unlike the effector procaspase‐3, procaspase‐9 cannot be processed by the apoptosome as a typical substrate. Indeed, procaspase‐9 possessed higher affinity for the apoptosome and could displace the processed caspase‐9 from the complex, thereby facilitating a Continuous Cycle of procaspase‐9 recruitment/activation, processing, and release from the complex. Owing to its rapid autocatalytic cleavage, however, procaspase‐9 per se contributed little to the activation of procaspase‐3. Thus, the Apaf‐1 apoptosome functions as a proteolytic‐based ‘molecular timer’, wherein the intracellular concentration of procaspase‐9 sets the overall duration of the timer, procaspase‐9 autoprocessing activates the timer, and the rate at which the processed caspase‐9 dissociates from the complex (and thus loses its capacity to activate procaspase‐3) dictates how fast the timer ‘ticks’ over.
Najiya Haque - One of the best experts on this subject based on the ideXlab platform.
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short term oral methylergonovine maleate prophylaxis for status migrainosus case series and review of literature
Frontiers in Neurology, 2019Co-Authors: Najiya Haque, Nauman TariqAbstract:Background Intravenous dihydroergotamine (DHE) is frequently used during inpatient hospitalizations or outpatient infusion therapies for 3-5 days in order to break the Continuous Cycle of status migrainosus. Long term use of ergots can cause safety concerns especially fibrosis. We tried a short term 7 days prophylaxis of oral methylergonovine after discharge in order to prevent status migrainosus relapse and extend the therapeutic benefit from IV DHE. Methods Patients were diagnosed with status migrainosus in clinic setting based on the ICHD-III criteria. They received IV DHE for 3-5 days followed by methylergonovine maleate oral tablets as prophylaxis for 7 days post discharge. They were asked to maintain their headache diaries which included data on headache frequency and intensity. A post discharge follow up at 1 week and 6-8 weeks was planned. Clinical improvement was defined as > 50% decrease in frequency and intensity of headaches. Intensity was graded on verbal numerical rating scale (VNRS) with 10 being the worst possible pain. Results A total of 3 patients who benefited from IV DHE, consented to trial of Methylergonovine Maleate 0.4 mg oral tablets three times a day prophylaxis on the day of discharge for a period of 7 days. At 1 week post discharge, all of the 3 patients had reported sustained improvement with severity dropping from an average of 8/10 intensity to 3/10 on VNRS. The headaches frequency had dropped from daily to episodic in 2 of the 3 patients. At an average of 7 weeks post discharge, 2 out of the 3 patients had reported sustained benefit. The third patient relapsed to the pre-admission status migrainosus severity. One patient reported mild diarrhea and nausea but was still able to continue the drug for a week. Conclusion Oral methylergonovine maleate prophylaxis for 7 days after IV DHE is feasible and safe for status migrainosus. This approach has the potential to prolonged the benefit of IV DHE and prevent relapse in to status migrainosus.
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Short Term Oral Methylergonovine Maleate Prophylaxis for Status Migrainosus. Case Series and Review of Literature
Frontiers Media S.A., 2019Co-Authors: Najiya Haque, Nauman TariqAbstract:Background: Intravenous dihydroergotamine (DHE) is frequently used during inpatient hospitalizations or outpatient infusion therapies for 3–5 days in order to break the Continuous Cycle of status migrainosus. We tried a short term 7 days prophylaxis of oral methylergonovine after discharge in order to prevent status migrainosus relapse and extend the therapeutic benefit from IV DHE.Methods: Patients were diagnosed with status migrainosus in clinic setting based on the ICHD-III criteria. They received 1 mg IV DHE every 8 h along with metoclopramide for 3–5 days followed by methylergonovine maleate oral tablets as prophylaxis for 7 days post discharge. They were asked to maintain their headache diaries which included data on headache frequency and intensity. A post discharge follow up at 1 and 68 weeks was planned. Clinical improvement was defined as >50% decrease in frequency and intensity of headaches. Intensity was graded on verbal numerical rating scale (VNRS) with 10 being the worst possible pain. The institutes IRB and ethics committee exempted this study from review given that it had only 3 patients.Results: A total of 3 patients 25–45 years of age who benefited from IV DHE, consented to trial of Methylergonovine Maleate 0.4 mg oral tablets three times a day prophylaxis on the day of discharge for a period of 7 days. At 1 week post discharge, all of the 3 patients had reported sustained improvement with severity dropping from an average of 8/10 intensity to 3/10 on VNRS. The headaches frequency had dropped from daily to episodic in 2 of the 3 patients. At an average of 7 weeks post discharge, 2 out of the 3 patients had reported sustained benefit. The third patient relapsed to the pre-admission status migrainosus severity. One patient reported mild diarrhea and nausea but was still able to continue the drug for a week.Conclusion: Methylergonovine maleate after 3–5 days of IV DHE infusions may be a feasible treatment strategy for status migrainosus. This approach has the potential to prolonged the benefit of IV DHE and prevent relapse in to status migrainosus
R E Geertsma - One of the best experts on this subject based on the ideXlab platform.
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medical technology at home safety related items in technical documentation
International Journal of Technology Assessment in Health Care, 2013Co-Authors: Ellen S M Hilbers, Claudette G J C A De Vries, R E GeertsmaAbstract:Advanced medical technologies are used in home settings to an increasing extent and this trend is expected to continue in the near future (1–3). Advantages are reduction of costs by shortening hospital stay, as well as improvement of quality of life for patients. However, home use of complex medical devices also brings new specific risks: Although intermittently supported by healthcare professionals, the patient, and lay carers have to operate the complex equipment themselves to a lesser or larger extent. Despite training provided, they have less medical and technical expertise and experience. Even home care professionals do not always have the opportunity to develop sufficient skills with all devices they may come across in daily practice. This may cause errors in operating complex devices, and inadequate dealing with alarms or unexpected situations. Pets and children, temperature and humidity extremes, dirt and dust, poor lightning, and limited space may interfere with safe and adequate device operation. Risks may also arise from changes in physical and cognitive capacities and emotional stability of patients and caregivers during the treatment period. Additionally, problems may be caused by improper storage, cleaning, maintenance, and calibration. There is no Continuous observation of the patient and, therefore, technical defects or medical problems may not be identified immediately and cannot always be solved as promptly as in an intramural setting (1;4;5). Problems with medical devices in home settings have indeed been reported over the past years (6–11). Risk analyses (RA) and instructions for use (IFU) for such devices should be adapted to the abovementioned, often use related, risks. Manufacturers of medical devices are obliged to perform a risk analysis, reduce risks as far as possible and provide clear instructions for use for their products, taking account of the training and knowledge level of the potential users (12). The European standard on application of risk management to medical devices (7) states: “The manufacturer shall establish, document, and maintain throughout the life-Cycle an ongoing process for identifying hazards associated with a medical device, estimating and evaluating the associated risks, controlling these risks, and monitoring the effectiveness of the controls.” Risks that cannot be eliminated by inherently safe design or construction, or reduced by adequate protection measures including alarms, are “residual risks” (RRs). Risks indicated in the RA as residual risks should be addressed on the label and/or in the IFU as warnings, precautions, or contraindications (WPCs), to ensure that the user is properly informed about these risks, and about how they can avoid hazardous situations by taking appropriate measures. On the other hand, all the WPCs that are mentioned in the IFU should originate from the RA as residual risks (13). Mutual coherence between RA and IFU is the extent to which residual risks in the RA and WPCs in the IFU are cross-referenced. The Medical Devices Directive (12) requires the device manufacturer to have “a systematic procedure to review experience gained from devices in the postproduction phase” and to take appropriate measures. This is called post market surveillance (PMS). PMS activities imply the systematic collection, analysis and interpretation of experiences with medical devices. A crucial aspect of PMS is gathering experiences by means of an active approach, including active customer feedback, post market clinical follow-up (where applicable) and literature reviews, in addition to handling of passive customer feedback, that is, complaints. Results of these activities have to be analyzed, and if relevant, changes should be made to the risk analysis, design, and/or IFU. This way a Continuous Cycle of improvement is maintained (14). In home treatment of patients with advanced technologies, many parties are involved, including industry, government agencies, health practitioners, lay carers, patients, and insurance companies. Acknowledgement of the risks by all the parties concerned, and adequate communication between all parties in the chain of care will enhance patient safety, as does the implementation of proper preventive measures. The Food and Drug Administration (FDA) has recently taken initiatives supporting patient safety in this setting (15). The Dutch National Institute for Public Health and the Environment (RIVM), an independent government institute for research and policy support, performed studies on safety-related aspects in technical documentation of manufacturers of medical equipment used in a home setting (6;10;11;16). An integrated survey of these studies is presented here.
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medical technology at home safety related items in technical documentation
International Journal of Technology Assessment in Health Care, 2013Co-Authors: Ellen S M Hilbers, Claudette G J C A De Vries, R E GeertsmaAbstract:Advanced medical technologies are used in home settings to an increasing extent and this trend is expected to continue in the near future (1–3). Advantages are reduction of costs by shortening hospital stay, as well as improvement of quality of life for patients. However, home use of complex medical devices also brings new specific risks: Although intermittently supported by healthcare professionals, the patient, and lay carers have to operate the complex equipment themselves to a lesser or larger extent. Despite training provided, they have less medical and technical expertise and experience. Even home care professionals do not always have the opportunity to develop sufficient skills with all devices they may come across in daily practice. This may cause errors in operating complex devices, and inadequate dealing with alarms or unexpected situations. Pets and children, temperature and humidity extremes, dirt and dust, poor lightning, and limited space may interfere with safe and adequate device operation. Risks may also arise from changes in physical and cognitive capacities and emotional stability of patients and caregivers during the treatment period. Additionally, problems may be caused by improper storage, cleaning, maintenance, and calibration. There is no Continuous observation of the patient and, therefore, technical defects or medical problems may not be identified immediately and cannot always be solved as promptly as in an intramural setting (1;4;5). Problems with medical devices in home settings have indeed been reported over the past years (6–11). Risk analyses (RA) and instructions for use (IFU) for such devices should be adapted to the abovementioned, often use related, risks. Manufacturers of medical devices are obliged to perform a risk analysis, reduce risks as far as possible and provide clear instructions for use for their products, taking account of the training and knowledge level of the potential users (12). The European standard on application of risk management to medical devices (7) states: “The manufacturer shall establish, document, and maintain throughout the life-Cycle an ongoing process for identifying hazards associated with a medical device, estimating and evaluating the associated risks, controlling these risks, and monitoring the effectiveness of the controls.” Risks that cannot be eliminated by inherently safe design or construction, or reduced by adequate protection measures including alarms, are “residual risks” (RRs). Risks indicated in the RA as residual risks should be addressed on the label and/or in the IFU as warnings, precautions, or contraindications (WPCs), to ensure that the user is properly informed about these risks, and about how they can avoid hazardous situations by taking appropriate measures. On the other hand, all the WPCs that are mentioned in the IFU should originate from the RA as residual risks (13). Mutual coherence between RA and IFU is the extent to which residual risks in the RA and WPCs in the IFU are cross-referenced. The Medical Devices Directive (12) requires the device manufacturer to have “a systematic procedure to review experience gained from devices in the postproduction phase” and to take appropriate measures. This is called post market surveillance (PMS). PMS activities imply the systematic collection, analysis and interpretation of experiences with medical devices. A crucial aspect of PMS is gathering experiences by means of an active approach, including active customer feedback, post market clinical follow-up (where applicable) and literature reviews, in addition to handling of passive customer feedback, that is, complaints. Results of these activities have to be analyzed, and if relevant, changes should be made to the risk analysis, design, and/or IFU. This way a Continuous Cycle of improvement is maintained (14). In home treatment of patients with advanced technologies, many parties are involved, including industry, government agencies, health practitioners, lay carers, patients, and insurance companies. Acknowledgement of the risks by all the parties concerned, and adequate communication between all parties in the chain of care will enhance patient safety, as does the implementation of proper preventive measures. The Food and Drug Administration (FDA) has recently taken initiatives supporting patient safety in this setting (15). The Dutch National Institute for Public Health and the Environment (RIVM), an independent government institute for research and policy support, performed studies on safety-related aspects in technical documentation of manufacturers of medical equipment used in a home setting (6;10;11;16). An integrated survey of these studies is presented here.