All-trans retinoic acid (ATRA) is a derivative of vitamin A and is the mainstay treatment of acute promyelocytic leukemia (APL). Hypercalcemia is a rare yet important side-effect of ATRA, especially when it is used concomitantly with a medication that impedes its metabolism by inhibiting cytochrome P-450 in the liver and thus increasing the duration of exposure to ATRA. Azole antifungal drugs such as voriconazole are frequently used in patients undergoing chemotherapy due to a high incidence of fungal infections. These medications inhibit two vital enzymes of cytochrome P-450, CYP2C9 and CYP3A4, potentiating the effects of ATRA on calcium metabolism. We present a case of a nine-year-old girl who underwent chemotherapy with all-trans retinoic acid for acute promyelocytic leukemia. The patient was given an anti-fungal cover with voriconazole for extensive fungal chest infection simultaneously. She was found to have asymptomatic hypercalcemia on routine follow-up during the consolidation phase. Both medications were stopped. Subsequently, she was admitted to the ward and managed conservatively with hydration. Serum calcium levels were returned to normal within six days after stopping the combination of ATRA and voriconazole. https://www.selleckchem.com/products/GDC-0941.html We underscore that the use of anti-fungal medications should be limited while using ATRA. However, strict monitoring must be done when a combination of these drugs is started, if necessary.Background Recent reports showed that overseas doctors were more likely than UK graduates to be referred by their employers to the General Medical Council (GMC). We investigated the trend of medico-legal insurance awareness and uptake of medical defence organisations (MDOs) by junior doctors and to examine if there is a difference between overseas and UK graduates. Methods Online questionnaire survey sent to junior doctors within the Yorkshire and Humber Deanery. Data regarding year of graduation, country of origin of primary medical qualification, year of starting work in the National Health Service (NHS) and date of joining an MDO were collected. Participant-identifiable information was not collected. Results A total of 202 junior doctors completed the survey 153 (76%) UK graduates and 49 (24%) overseas. Overseas doctors were less likely to know about MDO compared to UK graduates prior to working in the NHS (13 [26.5%] vs. 146 [95.4%]; p less then 0.0001). At the time of starting practice, MDO uptake was still significantly lower amongst overseas graduates (4 [8.2%] vs. 144 [94.1%]; p less then 0.0001). Uptake by overseas doctors increased after starting work to 33 (67.3%). However, despite improvement in MDO uptake, a significant number of overseas doctors still did not have independent cover compared with UK graduates (16 [32.7%] vs. 3 [2%]; p less then 0.0001). Conclusions Overseas graduates joining the NHS are still less likely to be aware of the requirement of adequate medico-legal cover and are less likely to join an MDO compared with UK graduates. Healthcare providers and regulators should work to decrease the existing gap and increase awareness amongst newly arrived overseas doctors.Radiology request forms are the basis of communication between referring physicians and radiologists. These are the sole documents on the basis of which a justification to carry out a radiological procedure is carried out. However, across the globe, there is a problem of inadequately filled radiology request forms. Several interventions like standardization and the use of technology have been proposed worldwide to overcome the shortcomings of inadequately filled radiology request forms. We carried out a two-phase audit assessing the impact of a technological intervention on the quality of radiology requests with the results showing marked improvement in key parameters. A subset analysis was also done to highlight the importance of radiology request forms by following the patients' treatment course. The remaining shortcomings highlight the importance of training sessions and refresher courses for junior doctors in order to familiarize them with the importance of adequately filled radiology request forms.Acute complications of pacemaker implantation such as lead dislodgement, pneumothorax, and myocardial perforation are not uncommon. Management of these usually requires reintervention. We herein describe lead perforation after a single chamber pacemaker implantation, which was successfully managed conservatively. This case underscores that vigilant monitoring post lead perforation can avoid a redo procedure.Most cases of non-bacterial thrombotic endocarditis (NBTE) tend to be related to malignancy or rheumatologic and autoimmune disorders like systemic lupus erythematosus. Rheumatoid arthritis (RA) itself has been associated with increased atherosclerosis, coronary artery plaque formation, and endothelial damage. However, it is rare to see NBTE in RA, simultaneously presenting with the acute coronary syndrome and acute limb ischemia due to distant embolization. Here we present a case of a 46-year-old female presenting with chest pain and right leg numbness, found to have ST-elevation myocardial infarction (STEMI) and occlusion of a peripheral artery due to embolization of vegetation present in the aortic valve. We also provide an extensive literature review of the relationship between NBTE and MI. One must be extra vigilant in managing these patients, especially if the size of vegetation is large as it has a tendency to embolize causing devastating complications.
Chronic alcohol use is a worldwide problem with multifaceted consequences including multiplying medical costs and sequelae, societal effects like drunk driving and assault, and lost economic productivity. These large-scale outcomes are driven by the consumption of ethanol, a small permeable molecule that has myriad effects in the human body, particularly in the liver and brain. In this review, we have summarized effects of acute and chronic alcohol consumption on epigenetic mechanisms that may drive pathobiology of Alcohol Use Disorder (AUD) while identifying areas of need for future research.
Epigenetics has emerged as an interesting field of biology at the intersection of genetics and the environment, and ethanol in particular has been identified as a potent modulator of the epigenome with various effects on DNA methylation, histone modifications, and non-coding RNAs. These changes alter chromatin dynamics and regulate gene expression that contribute to behavioral and physiological changes leading to the development of AUD psychopathology and cancer pathology.
All-trans retinoic acid (ATRA) is a derivative of vitamin A and is the mainstay treatment of acute promyelocytic leukemia (APL). Hypercalcemia is a rare yet important side-effect of ATRA, especially when it is used concomitantly with a medication that impedes its metabolism by inhibiting cytochrome P-450 in the liver and thus increasing the duration of exposure to ATRA. Azole antifungal drugs such as voriconazole are frequently used in patients undergoing chemotherapy due to a high incidence of fungal infections. These medications inhibit two vital enzymes of cytochrome P-450, CYP2C9 and CYP3A4, potentiating the effects of ATRA on calcium metabolism. We present a case of a nine-year-old girl who underwent chemotherapy with all-trans retinoic acid for acute promyelocytic leukemia. The patient was given an anti-fungal cover with voriconazole for extensive fungal chest infection simultaneously. She was found to have asymptomatic hypercalcemia on routine follow-up during the consolidation phase. Both medications were stopped. Subsequently, she was admitted to the ward and managed conservatively with hydration. Serum calcium levels were returned to normal within six days after stopping the combination of ATRA and voriconazole. https://www.selleckchem.com/products/GDC-0941.html We underscore that the use of anti-fungal medications should be limited while using ATRA. However, strict monitoring must be done when a combination of these drugs is started, if necessary.Background Recent reports showed that overseas doctors were more likely than UK graduates to be referred by their employers to the General Medical Council (GMC). We investigated the trend of medico-legal insurance awareness and uptake of medical defence organisations (MDOs) by junior doctors and to examine if there is a difference between overseas and UK graduates. Methods Online questionnaire survey sent to junior doctors within the Yorkshire and Humber Deanery. Data regarding year of graduation, country of origin of primary medical qualification, year of starting work in the National Health Service (NHS) and date of joining an MDO were collected. Participant-identifiable information was not collected. Results A total of 202 junior doctors completed the survey 153 (76%) UK graduates and 49 (24%) overseas. Overseas doctors were less likely to know about MDO compared to UK graduates prior to working in the NHS (13 [26.5%] vs. 146 [95.4%]; p less then 0.0001). At the time of starting practice, MDO uptake was still significantly lower amongst overseas graduates (4 [8.2%] vs. 144 [94.1%]; p less then 0.0001). Uptake by overseas doctors increased after starting work to 33 (67.3%). However, despite improvement in MDO uptake, a significant number of overseas doctors still did not have independent cover compared with UK graduates (16 [32.7%] vs. 3 [2%]; p less then 0.0001). Conclusions Overseas graduates joining the NHS are still less likely to be aware of the requirement of adequate medico-legal cover and are less likely to join an MDO compared with UK graduates. Healthcare providers and regulators should work to decrease the existing gap and increase awareness amongst newly arrived overseas doctors.Radiology request forms are the basis of communication between referring physicians and radiologists. These are the sole documents on the basis of which a justification to carry out a radiological procedure is carried out. However, across the globe, there is a problem of inadequately filled radiology request forms. Several interventions like standardization and the use of technology have been proposed worldwide to overcome the shortcomings of inadequately filled radiology request forms. We carried out a two-phase audit assessing the impact of a technological intervention on the quality of radiology requests with the results showing marked improvement in key parameters. A subset analysis was also done to highlight the importance of radiology request forms by following the patients' treatment course. The remaining shortcomings highlight the importance of training sessions and refresher courses for junior doctors in order to familiarize them with the importance of adequately filled radiology request forms.Acute complications of pacemaker implantation such as lead dislodgement, pneumothorax, and myocardial perforation are not uncommon. Management of these usually requires reintervention. We herein describe lead perforation after a single chamber pacemaker implantation, which was successfully managed conservatively. This case underscores that vigilant monitoring post lead perforation can avoid a redo procedure.Most cases of non-bacterial thrombotic endocarditis (NBTE) tend to be related to malignancy or rheumatologic and autoimmune disorders like systemic lupus erythematosus. Rheumatoid arthritis (RA) itself has been associated with increased atherosclerosis, coronary artery plaque formation, and endothelial damage. However, it is rare to see NBTE in RA, simultaneously presenting with the acute coronary syndrome and acute limb ischemia due to distant embolization. Here we present a case of a 46-year-old female presenting with chest pain and right leg numbness, found to have ST-elevation myocardial infarction (STEMI) and occlusion of a peripheral artery due to embolization of vegetation present in the aortic valve. We also provide an extensive literature review of the relationship between NBTE and MI. One must be extra vigilant in managing these patients, especially if the size of vegetation is large as it has a tendency to embolize causing devastating complications.
Chronic alcohol use is a worldwide problem with multifaceted consequences including multiplying medical costs and sequelae, societal effects like drunk driving and assault, and lost economic productivity. These large-scale outcomes are driven by the consumption of ethanol, a small permeable molecule that has myriad effects in the human body, particularly in the liver and brain. In this review, we have summarized effects of acute and chronic alcohol consumption on epigenetic mechanisms that may drive pathobiology of Alcohol Use Disorder (AUD) while identifying areas of need for future research.
Epigenetics has emerged as an interesting field of biology at the intersection of genetics and the environment, and ethanol in particular has been identified as a potent modulator of the epigenome with various effects on DNA methylation, histone modifications, and non-coding RNAs. These changes alter chromatin dynamics and regulate gene expression that contribute to behavioral and physiological changes leading to the development of AUD psychopathology and cancer pathology.
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