Sally Brady - Academia.edu (original) (raw)
Papers by Sally Brady
Journal of Clinical Pathology
Biotin interference in immunoassays using biotin-streptavidin binding technology is well recognis... more Biotin interference in immunoassays using biotin-streptavidin binding technology is well recognised by clinical laboratories, though the prevalence of elevated biotin in patient populations is largely unknown. We determined serum biotin concentrations in 4385 patient samples received sequentially by 6 laboratories for routine immunoassay analysis in England, and Korea, Singapore and Thailand (3 countries within the Asia Pacific region, APAC). Samples were initially analysed using a research use-only immunoassay, with those identified as having potentially elevated biotin concentrations referred for definitive analysis by LC-MS/MS. The prevalence of elevated serum biotin was 0.4% and 0.6% for England and APAC, respectively (range 10.0–129.0 µg/L). Our data adds to a report from a different region of England and is the first for APAC. Laboratories and clinicians benefit from an awareness of the prevalence of elevated serum biotin, which coupled with an understanding of the threshold a...
International Journal of Laboratory Hematology
Toxicologic Pathology, 2007
The investigations aimed to evaluate the usefulness of cardiac troponins as biomarkers of acute m... more The investigations aimed to evaluate the usefulness of cardiac troponins as biomarkers of acute myocardial injury in the rat. Serum from female Hanover Wistar rats treated with a single intraperitoneal (IP) injection of isoproterenol (ISO) was assayed for cardiac troponin I (cTnI) (ACS: 180SE, Bayer), cTnI (Immulite 2000, Diagnostic Products Corporation) and cardiac troponin T (cTnT) (Elecsys 2010, Roche). In a time-course study (50.0 mg/kg ISO), serum cTnI (ACS:180SE) and cTnT increased above control levels at 1 hour postdosing, peaking at 2 hours (cTnI, 4.30 microg/L; cTnT, 1.79 microg/L), and declined to baseline by 48 hours, with histologic cardiac lesions first seen at 4 hours postdosing. The Immulite 2000 assay gave minimal cTnI signals, indicating poor immunoreactivity towards rat cTnI. In a dose-response study (0.25 to 20.0 mg/kg ISO), there was a trend for increasing cTnI (ACS:180SE) values with increasing ISO dose levels at 2 hours postdosing. By 24 hours, cTnI levels returned to baseline although chronic cardiac myodegeneration was present. We conclude that serum cTnI and cTnT levels are sensitive and specific biomarkers for detecting ISO induced myocardial injury in the rat. Serum troponin values reflect the development of histopathologic lesions; however peak troponin levels precede maximal lesion severity.
Toxicologic Pathology, 2008
Postgraduate Medical Journal, 2021
To cite: Floyd CN, Brady S, Monteiro D, et al. Postgrad Med J Epub ahead of print: [please includ... more To cite: Floyd CN, Brady S, Monteiro D, et al. Postgrad Med J Epub ahead of print: [please include Day Month Year]. doi:10.1136/ postgradmedj-2020-139459 Department of Clinical Pharmacology, Guy’s and St Thomas’ Hospitals NHS Trust, London, UK King’s College London British Heart Foundation Centre, School of Cardiovascular Medicine and Sciences, King’s College London, London, UK Department of Chemical Pathology, Guy’s and St Thomas’ NHS Foundation Trust, London, UK Department of Special Haematology, Guy’s and St Thomas’ NHS Foundation Trust, London, UK Department of Diabetes, University Hospital, Lewisham and Greenwich Trust, London, UK Department of Clinical Biochemistry and Metabolic Medicine, Guy’s and St Thomas’ and Lewisham and Greenwich Trust, London, UK
Annals of Clinical Biochemistry, 2015
We investigated the kinetics of circulating biomarker elevation, specifically correlated with mor... more We investigated the kinetics of circulating biomarker elevation, specifically correlated with morphology in acute myocardial injury.Male Hanover Wistar rats underwent biomarker and morphologic cardiac evaluation at 0.5 to seventy-two hours after a single subcutaneous isoproterenol adminis-tration (100 or 4000mg/kg). Dose-dependent elevations of serumcardiac troponins I andT (cTnI, cTnT), and heart fatty acid–binding protein (H-FABP) occurred from 0.5 hour, peaked at two to three hours, and declined to baseline by twelve hours (H-FABP) or forty-eight to seventy-two hours (Serum cTns). They were more sensitive in detecting cardiomyocyte damage than other serum biomarkers. The Access 2 platform, an automated chemilumi-
Toxicologic Pathology, 2008
Tetrachlorodibenzo-p-dioxin (TCDD, or dioxin) and dioxin-like compounds (DLCs) induce numerous to... more Tetrachlorodibenzo-p-dioxin (TCDD, or dioxin) and dioxin-like compounds (DLCs) induce numerous toxicities, including developmental, endocrine, immunological, and multiorgan carcinogenic, in animals and/or humans. The National Toxicology Program (NTP) has conducted 4 murine carcinogenesis bioassays of TCDD in Swiss-Webster mice, Osborne-Mendel rats, B6C3F 1 mice, and female Harlan Sprague-Dawley rats. Two carcinogenesis studies of 3,3',4,4',5-pentachlorobiphenyl (PCB 126) or 2,3,4,7,8,-pentachlorodibenzofuran (PeCDF) in female Harlan Sprague-Dawley rats were also conducted, because humans are exposed daily to a combination of DLCs, primarily via ingestion of food. The Toxic Equivalency Factor was developed to evaluate health hazards caused by these mixtures. Herein we review the pathological effects reported in humans exposed to TCDD, PCB 126, and PeCDF and compare them to similar effects seen in NTP murine studies performed with the same compounds. In the NTP studies, TCDD, PCB126, and/or PeCDF induced neoplastic lesions (hepatocellular and/or cholangiolar, pancreatic, thyroidal, and pulmonary) and nonneoplastic alterations (hepatocellular and/or cholangiolar lesions in the liver, squamous hyperplasia in the oral cavity, cardiovascular damage, thyroid hypertrophy, and immunosuppression) similar to those reported in humans. While differences in specific pathologies were observed, clear consistency could be seen in the target organs affected (liver, oral cavity, cardiovascular system, immune system, thyroid, pancreas, and lung) in studies of both human and rodent toxicity and carcinogenicity.
Toxicologic Pathology, 2008
Tetrachlorodibenzo-p-dioxin (TCDD, or dioxin) and dioxin-like compounds (DLCs) induce numerous to... more Tetrachlorodibenzo-p-dioxin (TCDD, or dioxin) and dioxin-like compounds (DLCs) induce numerous toxicities, including developmental, endocrine, immunological, and multiorgan carcinogenic, in animals and/or humans. The National Toxicology Program (NTP) has conducted 4 murine carcinogenesis bioassays of TCDD in Swiss-Webster mice, Osborne-Mendel rats, B6C3F 1 mice, and female Harlan Sprague-Dawley rats. Two carcinogenesis studies of 3,3',4,4',5-pentachlorobiphenyl (PCB 126) or 2,3,4,7,8,-pentachlorodibenzofuran (PeCDF) in female Harlan Sprague-Dawley rats were also conducted, because humans are exposed daily to a combination of DLCs, primarily via ingestion of food. The Toxic Equivalency Factor was developed to evaluate health hazards caused by these mixtures. Herein we review the pathological effects reported in humans exposed to TCDD, PCB 126, and PeCDF and compare them to similar effects seen in NTP murine studies performed with the same compounds. In the NTP studies, TCDD, PCB126, and/or PeCDF induced neoplastic lesions (hepatocellular and/or cholangiolar, pancreatic, thyroidal, and pulmonary) and nonneoplastic alterations (hepatocellular and/or cholangiolar lesions in the liver, squamous hyperplasia in the oral cavity, cardiovascular damage, thyroid hypertrophy, and immunosuppression) similar to those reported in humans. While differences in specific pathologies were observed, clear consistency could be seen in the target organs affected (liver, oral cavity, cardiovascular system, immune system, thyroid, pancreas, and lung) in studies of both human and rodent toxicity and carcinogenicity.
Toxicologic Pathology, 2010
The current studies demonstrate the effect of low-dose intraperitoneal (IP) administration of iso... more The current studies demonstrate the effect of low-dose intraperitoneal (IP) administration of isoprotenerol (ISO) and subcutaneous (SC) versus IP routes of administration of ISO on serum cardiac troponin I (cTnI) levels in female Hanover Wistar rats, providing additional evidence to support acceptance of cTnI as a cardiac biomarker. At 2 hr postdosing with 0-500 mg/kg ISO, mean serum cTnI levels were increased in a dose-related fashion at !10 mg/kg with no evidence of cardiac pathology. At 24 h, cTnI concentrations were generally at control levels, but histologic cardiomyocyte injury was evident in a proportion of the animals given !10 mg/kg. In a second experiment, rats given SC ISO at 5,000 mg/kg and necropsied at 0, 1, 2, and 4 hr postdosing had higher levels of serum cTnI than animals given the same dose IP.
Toxicologic Pathology, Jun 28, 2010
We investigated the kinetics of circulating biomarker elevation, specifically correlated with mor... more We investigated the kinetics of circulating biomarker elevation, specifically correlated with morphology in acute myocardial injury. Male Hanover Wistar rats underwent biomarker and morphologic cardiac evaluation at 0.5 to seventy-two hours after a single subcutaneous isoproterenol administration (100 or 4000 mg/kg). Dose-dependent elevations of serum cardiac troponins I and T (cTnI, cTnT), and heart fatty acid-binding protein (H-FABP) occurred from 0.5 hour, peaked at two to three hours, and declined to baseline by twelve hours (H-FABP) or forty-eight to seventy-two hours (Serum cTns). They were more sensitive in detecting cardiomyocyte damage than other serum biomarkers. The Access 2 platform, an automated chemiluminescence analyzer (Beckman Coulter), showed the greatest cTnI fold-changes and low range sensitivity. Myocardial injury was detected morphologically from 0.5 hour, correlating well with loss of cTnI immunoreactivity and serum biomarker elevation at early time points. Ultrastructurally, there was no evidence of cardiomyocyte death at 0.5 hour. After three hours, a clear temporal disconnect occurred: lesion scores increased with declining cTnI, cTnT, and H-FABP values. Serum cTns are sensitive and specific markers for detecting acute/active cardiomyocyte injury in this rat model. Heart fatty acid-binding protein is a good early marker but is less sensitive and nonspecific. Release of these biomarkers begins early in myocardial injury, prior to necrosis. Assessment of cTn merits increased consideration for routine screening of acute/ongoing cardiomyocyte injury in rat toxicity studies.
Journal of Clinical Pathology
Biotin interference in immunoassays using biotin-streptavidin binding technology is well recognis... more Biotin interference in immunoassays using biotin-streptavidin binding technology is well recognised by clinical laboratories, though the prevalence of elevated biotin in patient populations is largely unknown. We determined serum biotin concentrations in 4385 patient samples received sequentially by 6 laboratories for routine immunoassay analysis in England, and Korea, Singapore and Thailand (3 countries within the Asia Pacific region, APAC). Samples were initially analysed using a research use-only immunoassay, with those identified as having potentially elevated biotin concentrations referred for definitive analysis by LC-MS/MS. The prevalence of elevated serum biotin was 0.4% and 0.6% for England and APAC, respectively (range 10.0–129.0 µg/L). Our data adds to a report from a different region of England and is the first for APAC. Laboratories and clinicians benefit from an awareness of the prevalence of elevated serum biotin, which coupled with an understanding of the threshold a...
International Journal of Laboratory Hematology
Toxicologic Pathology, 2007
The investigations aimed to evaluate the usefulness of cardiac troponins as biomarkers of acute m... more The investigations aimed to evaluate the usefulness of cardiac troponins as biomarkers of acute myocardial injury in the rat. Serum from female Hanover Wistar rats treated with a single intraperitoneal (IP) injection of isoproterenol (ISO) was assayed for cardiac troponin I (cTnI) (ACS: 180SE, Bayer), cTnI (Immulite 2000, Diagnostic Products Corporation) and cardiac troponin T (cTnT) (Elecsys 2010, Roche). In a time-course study (50.0 mg/kg ISO), serum cTnI (ACS:180SE) and cTnT increased above control levels at 1 hour postdosing, peaking at 2 hours (cTnI, 4.30 microg/L; cTnT, 1.79 microg/L), and declined to baseline by 48 hours, with histologic cardiac lesions first seen at 4 hours postdosing. The Immulite 2000 assay gave minimal cTnI signals, indicating poor immunoreactivity towards rat cTnI. In a dose-response study (0.25 to 20.0 mg/kg ISO), there was a trend for increasing cTnI (ACS:180SE) values with increasing ISO dose levels at 2 hours postdosing. By 24 hours, cTnI levels returned to baseline although chronic cardiac myodegeneration was present. We conclude that serum cTnI and cTnT levels are sensitive and specific biomarkers for detecting ISO induced myocardial injury in the rat. Serum troponin values reflect the development of histopathologic lesions; however peak troponin levels precede maximal lesion severity.
Toxicologic Pathology, 2008
Postgraduate Medical Journal, 2021
To cite: Floyd CN, Brady S, Monteiro D, et al. Postgrad Med J Epub ahead of print: [please includ... more To cite: Floyd CN, Brady S, Monteiro D, et al. Postgrad Med J Epub ahead of print: [please include Day Month Year]. doi:10.1136/ postgradmedj-2020-139459 Department of Clinical Pharmacology, Guy’s and St Thomas’ Hospitals NHS Trust, London, UK King’s College London British Heart Foundation Centre, School of Cardiovascular Medicine and Sciences, King’s College London, London, UK Department of Chemical Pathology, Guy’s and St Thomas’ NHS Foundation Trust, London, UK Department of Special Haematology, Guy’s and St Thomas’ NHS Foundation Trust, London, UK Department of Diabetes, University Hospital, Lewisham and Greenwich Trust, London, UK Department of Clinical Biochemistry and Metabolic Medicine, Guy’s and St Thomas’ and Lewisham and Greenwich Trust, London, UK
Annals of Clinical Biochemistry, 2015
We investigated the kinetics of circulating biomarker elevation, specifically correlated with mor... more We investigated the kinetics of circulating biomarker elevation, specifically correlated with morphology in acute myocardial injury.Male Hanover Wistar rats underwent biomarker and morphologic cardiac evaluation at 0.5 to seventy-two hours after a single subcutaneous isoproterenol adminis-tration (100 or 4000mg/kg). Dose-dependent elevations of serumcardiac troponins I andT (cTnI, cTnT), and heart fatty acid–binding protein (H-FABP) occurred from 0.5 hour, peaked at two to three hours, and declined to baseline by twelve hours (H-FABP) or forty-eight to seventy-two hours (Serum cTns). They were more sensitive in detecting cardiomyocyte damage than other serum biomarkers. The Access 2 platform, an automated chemilumi-
Toxicologic Pathology, 2008
Tetrachlorodibenzo-p-dioxin (TCDD, or dioxin) and dioxin-like compounds (DLCs) induce numerous to... more Tetrachlorodibenzo-p-dioxin (TCDD, or dioxin) and dioxin-like compounds (DLCs) induce numerous toxicities, including developmental, endocrine, immunological, and multiorgan carcinogenic, in animals and/or humans. The National Toxicology Program (NTP) has conducted 4 murine carcinogenesis bioassays of TCDD in Swiss-Webster mice, Osborne-Mendel rats, B6C3F 1 mice, and female Harlan Sprague-Dawley rats. Two carcinogenesis studies of 3,3',4,4',5-pentachlorobiphenyl (PCB 126) or 2,3,4,7,8,-pentachlorodibenzofuran (PeCDF) in female Harlan Sprague-Dawley rats were also conducted, because humans are exposed daily to a combination of DLCs, primarily via ingestion of food. The Toxic Equivalency Factor was developed to evaluate health hazards caused by these mixtures. Herein we review the pathological effects reported in humans exposed to TCDD, PCB 126, and PeCDF and compare them to similar effects seen in NTP murine studies performed with the same compounds. In the NTP studies, TCDD, PCB126, and/or PeCDF induced neoplastic lesions (hepatocellular and/or cholangiolar, pancreatic, thyroidal, and pulmonary) and nonneoplastic alterations (hepatocellular and/or cholangiolar lesions in the liver, squamous hyperplasia in the oral cavity, cardiovascular damage, thyroid hypertrophy, and immunosuppression) similar to those reported in humans. While differences in specific pathologies were observed, clear consistency could be seen in the target organs affected (liver, oral cavity, cardiovascular system, immune system, thyroid, pancreas, and lung) in studies of both human and rodent toxicity and carcinogenicity.
Toxicologic Pathology, 2008
Tetrachlorodibenzo-p-dioxin (TCDD, or dioxin) and dioxin-like compounds (DLCs) induce numerous to... more Tetrachlorodibenzo-p-dioxin (TCDD, or dioxin) and dioxin-like compounds (DLCs) induce numerous toxicities, including developmental, endocrine, immunological, and multiorgan carcinogenic, in animals and/or humans. The National Toxicology Program (NTP) has conducted 4 murine carcinogenesis bioassays of TCDD in Swiss-Webster mice, Osborne-Mendel rats, B6C3F 1 mice, and female Harlan Sprague-Dawley rats. Two carcinogenesis studies of 3,3',4,4',5-pentachlorobiphenyl (PCB 126) or 2,3,4,7,8,-pentachlorodibenzofuran (PeCDF) in female Harlan Sprague-Dawley rats were also conducted, because humans are exposed daily to a combination of DLCs, primarily via ingestion of food. The Toxic Equivalency Factor was developed to evaluate health hazards caused by these mixtures. Herein we review the pathological effects reported in humans exposed to TCDD, PCB 126, and PeCDF and compare them to similar effects seen in NTP murine studies performed with the same compounds. In the NTP studies, TCDD, PCB126, and/or PeCDF induced neoplastic lesions (hepatocellular and/or cholangiolar, pancreatic, thyroidal, and pulmonary) and nonneoplastic alterations (hepatocellular and/or cholangiolar lesions in the liver, squamous hyperplasia in the oral cavity, cardiovascular damage, thyroid hypertrophy, and immunosuppression) similar to those reported in humans. While differences in specific pathologies were observed, clear consistency could be seen in the target organs affected (liver, oral cavity, cardiovascular system, immune system, thyroid, pancreas, and lung) in studies of both human and rodent toxicity and carcinogenicity.
Toxicologic Pathology, 2010
The current studies demonstrate the effect of low-dose intraperitoneal (IP) administration of iso... more The current studies demonstrate the effect of low-dose intraperitoneal (IP) administration of isoprotenerol (ISO) and subcutaneous (SC) versus IP routes of administration of ISO on serum cardiac troponin I (cTnI) levels in female Hanover Wistar rats, providing additional evidence to support acceptance of cTnI as a cardiac biomarker. At 2 hr postdosing with 0-500 mg/kg ISO, mean serum cTnI levels were increased in a dose-related fashion at !10 mg/kg with no evidence of cardiac pathology. At 24 h, cTnI concentrations were generally at control levels, but histologic cardiomyocyte injury was evident in a proportion of the animals given !10 mg/kg. In a second experiment, rats given SC ISO at 5,000 mg/kg and necropsied at 0, 1, 2, and 4 hr postdosing had higher levels of serum cTnI than animals given the same dose IP.
Toxicologic Pathology, Jun 28, 2010
We investigated the kinetics of circulating biomarker elevation, specifically correlated with mor... more We investigated the kinetics of circulating biomarker elevation, specifically correlated with morphology in acute myocardial injury. Male Hanover Wistar rats underwent biomarker and morphologic cardiac evaluation at 0.5 to seventy-two hours after a single subcutaneous isoproterenol administration (100 or 4000 mg/kg). Dose-dependent elevations of serum cardiac troponins I and T (cTnI, cTnT), and heart fatty acid-binding protein (H-FABP) occurred from 0.5 hour, peaked at two to three hours, and declined to baseline by twelve hours (H-FABP) or forty-eight to seventy-two hours (Serum cTns). They were more sensitive in detecting cardiomyocyte damage than other serum biomarkers. The Access 2 platform, an automated chemiluminescence analyzer (Beckman Coulter), showed the greatest cTnI fold-changes and low range sensitivity. Myocardial injury was detected morphologically from 0.5 hour, correlating well with loss of cTnI immunoreactivity and serum biomarker elevation at early time points. Ultrastructurally, there was no evidence of cardiomyocyte death at 0.5 hour. After three hours, a clear temporal disconnect occurred: lesion scores increased with declining cTnI, cTnT, and H-FABP values. Serum cTns are sensitive and specific markers for detecting acute/active cardiomyocyte injury in this rat model. Heart fatty acid-binding protein is a good early marker but is less sensitive and nonspecific. Release of these biomarkers begins early in myocardial injury, prior to necrosis. Assessment of cTn merits increased consideration for routine screening of acute/ongoing cardiomyocyte injury in rat toxicity studies.