Karl Anderson | University of Texas, Medical Branch at Galveston (original) (raw)

Papers by Karl Anderson

Research paper thumbnail of Final results from a phase 1/2, 48-month, open-label extension study of givosiran in patients with acute intermittent porphyria

Research paper thumbnail of Twelve-Month Interim Analysis of Efficacy and Safety of Givosiran, an Investigational Rnai Therapeutic for Acute Hepatic Porphyria, in the Envision Open Label Extension

Hematology, Transfusion and Cell Therapy, 2020

Research paper thumbnail of Effect of charcoal‐broiled beef on antipyrine and theophylline metabolism

Clinical Pharmacology & Therapeutics, 1978

Eight healthy volunteers were sequentially fed a control diet, a charcoal‐broiled beef‐containing... more Eight healthy volunteers were sequentially fed a control diet, a charcoal‐broiled beef‐containing diet, and the control diet a second time. The mean plasma half‐lives (t½) of antipyrine and theophylline were each decreased by 22% after the subjects were fed the charcoal‐broiled beef‐containing diet. The mean plasma t½s for these drugs returned to control values when the subjects were fed the control diet for a second time. Considerable individuality occurred in the responsiveness of the subjects to the charcoal‐broiled beef‐containing diet. The decreases in antipyrine plasma t½s among the 8 subjects ranged from 5% to 39%, and the decreases in theophylline t½S ranged from 0% to 42%.

Research paper thumbnail of The Porphyrias

Inborn Metabolic Diseases, 2000

Research paper thumbnail of Lead hazard among ironworkers. Dismantling lead-painted elevated subway line in New York City

New York state journal of medicine, 1978

Flame cutting of lead-painted steel structures may be associated with considerable lead exposure.... more Flame cutting of lead-painted steel structures may be associated with considerable lead exposure. In this study, an outbreak of lead poisoning among ironworkers dismantling an elevated subway line in New York City is described. Industrial hygiene evaluation of the respirators showed that inadequate equipment was the cause of the subsequent occupational disease. In the assessment of the lead-induced effects on the hematopoietic system, a new screening test--erythrocyte zinc protoporphyrin determination--was employed, utilizing a portable field device (hematofluorometer) on which an instantaneous reading of ZPP (zinc protoporphyrin) concentration is obtained. Correlative data between ZPP and blood lead are presented, demonstrating that ZPP determinations may improve and simplify the task of screening and monitoring populations chronically exposed to lead. The effect of lead on the biosynthesis of heme was also assessed in five workers, by investigating the functional capacity of the hepatic cytochrome P-450 system through drug metabolism studies before and after chelation therapy. The effect on this system was considered minimal. Environmental studies showed that very high amounts of lead dusts were generated by the demolition process, but did not present any significant hazard to people residing in the vicinity. It is emphasized that combined medical and industrial hygiene surveillance is more » essential for the safe management of such work operation, and workers engaged in such operations require proper respiratory equipment to minimize the risk of increased lead absorption. « less

Research paper thumbnail of Interactions between nutritional factors and drug biotransformations in man

Proceedings of the National Academy of Sciences of the United States of America, Jul 1, 1976

This study was undertaken to examine the influence of nutritional factors on the activity of the ... more This study was undertaken to examine the influence of nutritional factors on the activity of the mixed function oxidase system in man, which is cytochrome P450 dependent. Three normal volunteers were fed a low carbohydrate-high protein diet for 2 weeks, followed by a high carbohydrate-low protein diet for the following 2 weeks. At the end of each test diet period, the plasma elimination rates of antipyrine and theophylline were determined. The mean plasma half-life for antipyrine was 17.5 hr on the high carbohydrate-low protein diet and 9.2 hr on the low carbohydrate-high protein diet. The mean plasma half-life for theophylline was 8.9 hr on the high carbohydrate-low protein diet and 5.9 iwr on the low carbohydrate-high protein diet. These data demonstrate marked influences of dietary carbohydrate and/or protein ingestion on oxidative biotransformation of drugs in man. The effects of changes in dietary macronutrient composition on the hepatic microsomal enzymes that metabolize drugs, other foreign chemicals, and endogenous compounds, such as steroid hormones, have been studied extensively in animals (1). These studies show that dietary macronutrient composition, as well as the presence of contaminants and food additives, can influence the activities of these enzymes. Although dietary composition has been shown to be an important environmental determinant in the response of the experimental animal to pharmacological agents, such studies are lacking in man. A significant proportion of normal subjects manipulate their diets in weight-reducing regimens. Similarly, dietary treatments in clinical conditions, including obesity, atherosclerosis, and diabetes, are considered to play a significant role in the management of such disease problems. It is the purpose of these studies

Research paper thumbnail of Key terms and definitions in acute porphyrias: Results of an international Delphi consensus led by the European porphyria network

Journal of Inherited Metabolic Disease

Acute porphyrias are a group of rare inherited disorders causing acute neurovisceral attacks. Man... more Acute porphyrias are a group of rare inherited disorders causing acute neurovisceral attacks. Many terms used frequently in the literature and clinical practice are ambiguous, which can lead to confusion in the way patients are managed, studied, and reported in clinical studies. Agreed definitions are a necessary first step in developing management guidelines and will facilitate communication of results of future clinical research. The Delphi method was used to generate consensus on key terms and definitions in acute porphyria. The process started with a brainstorming phase offered to all members of the European Porphyria Network followed by two Delphi rounds among international experts in the field of porphyria (the Acute Porphyria Expert Panel). A consensus of 75% or more was defined as the agreement threshold. A total of 63 respondents from 26 countries participated in the brainstorming phase, leading to the choice of nine terms and definitions. A total of 34 experts were invited...

Research paper thumbnail of Light-Related Cutaneous Symptoms of Erythropoietic Protoporphyria and Associations With Light Sensitivity Measurements

JAMA Dermatology

ImportanceErythropoietic protoporphyria (EPP) is a rare and underdiagnosed genetic disease charac... more ImportanceErythropoietic protoporphyria (EPP) is a rare and underdiagnosed genetic disease characterized by painful sensitivity to light. A better understanding and characterization of its light-induced cutaneous symptoms may aid in the identification of EPP in patients.ObjectivesTo describe the cutaneous symptoms of erythropoietic protoporphyria (EPP) and to determine if these symptoms are associated with the degree of light sensitivity.Design, Setting, and ParticipantsThis was a cross-sectional study of adolescent and adult (≥15 years) patients with EPP across the US conducted by a single academic hospital via a remotely administered survey, measurements of light sensitivity by light dosimetry and by text message symptom assessments. Data analyses were conducted from November 2020 to April 2022.ExposuresSunlight exposure.Main Outcomes and MeasuresSelf-reported symptoms and association with measured light sensitivity.ResultsThe study sample consisted of 35 patients with EPP (mean [...

Research paper thumbnail of Prospective observational pilot study of quantitative light dosimetry in erythropoietic protoporphyria

Journal of the American Academy of Dermatology

Research paper thumbnail of Disorders of Haem Biosynthesis

Research paper thumbnail of Porphyrin Accumulation and Biliary Lithiasis Causing Diffusely Black Livers in Broiler Chickens

Research paper thumbnail of Dietary pectin and cellulose effects on hepatic and intestinal mixed-function oxidations and hepatic HMG-CoA reductase

Research paper thumbnail of Biochemical Diagnosis of Acute Hepatic Porphyria: Updated Expert Recommendations for Primary Care Physicians

The American Journal of the Medical Sciences, 2021

Acute hepatic porphyria (AHP) is a group of rare, metabolic diseases where patients can experienc... more Acute hepatic porphyria (AHP) is a group of rare, metabolic diseases where patients can experience acute neurovisceral attacks, chronic symptoms, and long-term complications. Diagnostic biochemical testing is widely available and effective, but a substantial time from symptom onset to diagnosis often delays treatment and increases morbidity. A panel of laboratory scientists and clinical AHP specialists collaborated to produce recommendations on how to enhance biochemical diagnosis of AHP in the USA. AHP should be considered in the differential diagnosis of unexplained abdominal pain, the most common symptom, soon after excluding common causes. Measurement of porphobilinogen (PBG) and porphyrins in a random urine sample, with results normalized to creatinine, is recommended as an effective and cost-efficient initial test for AHP. Delta-aminolevulinic acid testing may be included but is not essential. The optimal time to collect a urine sample is during an attack. Substantial PBG elevation confirms an AHP diagnosis and allows for prompt treatment initiation. Additional testing can determine AHP subtype and identify at-risk family members. Increased awareness of AHP and correct diagnostic methods will reduce diagnostic delay and improve patient outcomes.

Research paper thumbnail of Expanding Experience With Liver Transplantation in Acute Intermittent Porphyria

Liver Transplantation, 2021

Acute intermittent porphyria (AIP) is a rare autosomal dominant hepatic disease with potentially ... more Acute intermittent porphyria (AIP) is a rare autosomal dominant hepatic disease with potentially severe and potential fatal neurological manifestations. In the current issue, Lissing et. al. confirm that marked improvement can occur following liver transplantation(LT) (1). AIP results from heterozygous deficiency of the third of eight enzymes in the heme biosynthetic pathway. Attacks of neurovisceral symptoms occur when exacerbating factors upregulate the first and rate limiting enzyme of the pathway (5-aminolevulinic acid synthase 1 - ALAS1) in the liver, causing accumulation of the porphyrin precursors 5-aminolevulinic acid (ALA) and porphobilinogen (PBG).

Research paper thumbnail of A Phase 1/2 Open Label Extension Study of Givosiran, an Investigational Rnai Therapeutic, in Patients with Acute Intermittent Porphyria

Hematology, Transfusion and Cell Therapy, 2020

Background and Aims: Porto sinusoidal vascular liver disease (PSVD) represents a cause of presinu... more Background and Aims: Porto sinusoidal vascular liver disease (PSVD) represents a cause of presinusoidal portal hypertension which can often lead to formation of oesophageal or gastric varices and portal hypertension related bleeding. In cirrhotic patients, liver stiffness measurement by transient elastography (LSM) < 20 kPa and platelets (PLT) count >150.000 are able to rule-out high risk oesophageal varices. However, in patients PSVD there is no noninvasive test that can predict the presence of varices. We aimed to investigate whether LSM, spleen stiffness measurement (SSM) and PLT count have a role in prediction of varices in patients with PSVD. Method: Patients diagnosed with PSVD who were admitted at the RIGH 'Prof. dr. Octavian Fodor' and who had performed endoscopies prior to or at enrolment were included in the study. All patients had routine laboratory work out and performed liver and spleen measurements by transient elastography with a Fibroscan 502 Touch ® (M or XL probe). The median of 10 measurements with an IQR < 0.3 was considered adequate. A control group of cirrhotic of various etiologies compensated patients was also included in the study. Results: Nineteen patients with biopsy proven PSVD were included in the study. Mean age was 34.79 years [range 19-72] and included 57.9% of male patients. All patients were Child Pugh A and had a mean MELD score of 9.31 [range 6-17], mean PLT level was 120.000 [range 12.000-325.000]. Fifteen patients of the patients had varices, either esophageal (n = 11), gastric (n = 2) or both (n = 1). Mean LSM was 9.3 kPa [range 3-39.7] and mean SSM was 46.9 kPa [11.8-75]. The ratio between the difference of SSM and LSM and PLT count ((SSM-LSM)/ PLT) was the best test to predict the presence of varices with an AUROC of 0.83 CI 95% (0.64-1), p = 0.04. If the (SSM-LSM)/PLT ratio was <0.06, the test had a sensitivity of 100%, specificity of 25%, a PPV of 83% and a NPV of 100% with a +L = 1.33 and a-LR = 0 in prediction of varices. The test had a diagnostic accuracy of 84.2% (16 / 19). If the (SSM-LSM)/PLT ration was > = 0.29, the test had a sensitivity of 66%, specificity of 100%, a PPV of 100% and a NPV of 44% with a + L = infinite and a-LR = 0.33 in prediction of varices. When this ratio was tested in the cirrhotic population, the AUROC was 0.32 CI 95% (0.13-0.53), p = 0.13. Conclusion: The ratio of (SSM-LSM)/PLT has a high accuracy for predicting esophageal or gastric varices in patients with porto sinusoidal vascular liver disease, but not for patients with compensated cirrhosis. At a cutoff of 0.06, the test has a very large effect on ruling-out and at a cutoff of 0.29 the test has a very large effect on ruling-in the presence of varices in this disorder. In these patients, according to these cutoffs , endoscopies should be performed if the ratio is between 0.06 and 0.29. Due to small sample size and high prevalence of varices, these results need confirmation in a larger cohort.

Research paper thumbnail of Overall Health, Daily Functioning, and Quality of Life in Acute Hepatic Porphyria Patients: ENVISION, a Phase 3 Global, Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial

Digestive and Liver Disease, 2020

Research paper thumbnail of 996 Disease Characteristics of Acute Hepatic Porphyria Patients: ENVISION, a Phase 3 Global, Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial

American Journal of Gastroenterology, 2019

INTRODUCTION: Acute Hepatic Porphyria (AHP) is a family of rare genetic diseases due to enzyme de... more INTRODUCTION: Acute Hepatic Porphyria (AHP) is a family of rare genetic diseases due to enzyme deficiencies in heme biosynthesis in the liver that can lead to neurovisceral attacks and chronic symptoms. (1, 2) AHP is also associated with multiple long-term complications, including neuropathy (3,4), hypertension (5,6), chronic kidney disease (7), and hepatocellular carcinoma (8,9). METHODS: ENVISION (NCT03338816) was a Phase 3 global, multicenter, randomized, double-blind, placebo-controlled trial with an open label extension to evaluate the efficacy and safety of subcutaneous givosiran in AHP. Eligible patients had an AHP diagnosis and ≥2 attacks within the prior 6 months. At baseline detailed medical history and laboratory assessments were obtained. RESULTS: Ninety-four AHP patients enrolled, median (range) age 37.5 (19-65) years, 89% female, and median (range) of 6.5 (0.1–43) years since diagnosis. Patients had a median of 4 composite attacks in the preceding 6 months and 40% were...

Research paper thumbnail of 38 Prolongation of the Biochemical Effects and Clearance of Heme by Tin Mesoporphyrin in Acute Porphyria

Journal of Investigative Medicine, 2004

Research paper thumbnail of Disorders of Haem Biosynthesis

Inborn Metabolic Diseases, 2016

Research paper thumbnail of Lead intoxication: Effects on cytochrome P‐450‐mediated hepatic oxidations

Clinical Pharmacology & Therapeutics, 1976

Acute administration of lead to rats caused significant decreases in cytochrome P‐450, ethylmorph... more Acute administration of lead to rats caused significant decreases in cytochrome P‐450, ethylmorphine N‐demethylase, and aniline hydroxylase activities and prolonged hexobarbital‐induced sleeping times. However, chronic administration of lead to weanling rats caused no significant changes in hepatic cytochrome P‐450 levels or in the microsomal oxidative enzymes over a 12‐wk period. Eight patients exposed to lead in the process of burning through lead‐painted steel structures for at least 3 mo showed marked effects of chronic lead intoxication on the erythropoietic system: inhibition of erythrocyte δ‐aminolevulinic acid dehydratase, increased erythrocyte protoporphyrin levels, and increased urinary excretion of δ‐aminolevulinic acid. Chelation therapy greatly alleviated the inhibitory effects on dehydratase activity and decreased urinary δ‐aminolevulinic acid excretion. The plasma elimination rate of antipyrine, a drug primarily metabolized by hepatic microsomal enzymes, was determine...

Research paper thumbnail of Final results from a phase 1/2, 48-month, open-label extension study of givosiran in patients with acute intermittent porphyria

Research paper thumbnail of Twelve-Month Interim Analysis of Efficacy and Safety of Givosiran, an Investigational Rnai Therapeutic for Acute Hepatic Porphyria, in the Envision Open Label Extension

Hematology, Transfusion and Cell Therapy, 2020

Research paper thumbnail of Effect of charcoal‐broiled beef on antipyrine and theophylline metabolism

Clinical Pharmacology & Therapeutics, 1978

Eight healthy volunteers were sequentially fed a control diet, a charcoal‐broiled beef‐containing... more Eight healthy volunteers were sequentially fed a control diet, a charcoal‐broiled beef‐containing diet, and the control diet a second time. The mean plasma half‐lives (t½) of antipyrine and theophylline were each decreased by 22% after the subjects were fed the charcoal‐broiled beef‐containing diet. The mean plasma t½s for these drugs returned to control values when the subjects were fed the control diet for a second time. Considerable individuality occurred in the responsiveness of the subjects to the charcoal‐broiled beef‐containing diet. The decreases in antipyrine plasma t½s among the 8 subjects ranged from 5% to 39%, and the decreases in theophylline t½S ranged from 0% to 42%.

Research paper thumbnail of The Porphyrias

Inborn Metabolic Diseases, 2000

Research paper thumbnail of Lead hazard among ironworkers. Dismantling lead-painted elevated subway line in New York City

New York state journal of medicine, 1978

Flame cutting of lead-painted steel structures may be associated with considerable lead exposure.... more Flame cutting of lead-painted steel structures may be associated with considerable lead exposure. In this study, an outbreak of lead poisoning among ironworkers dismantling an elevated subway line in New York City is described. Industrial hygiene evaluation of the respirators showed that inadequate equipment was the cause of the subsequent occupational disease. In the assessment of the lead-induced effects on the hematopoietic system, a new screening test--erythrocyte zinc protoporphyrin determination--was employed, utilizing a portable field device (hematofluorometer) on which an instantaneous reading of ZPP (zinc protoporphyrin) concentration is obtained. Correlative data between ZPP and blood lead are presented, demonstrating that ZPP determinations may improve and simplify the task of screening and monitoring populations chronically exposed to lead. The effect of lead on the biosynthesis of heme was also assessed in five workers, by investigating the functional capacity of the hepatic cytochrome P-450 system through drug metabolism studies before and after chelation therapy. The effect on this system was considered minimal. Environmental studies showed that very high amounts of lead dusts were generated by the demolition process, but did not present any significant hazard to people residing in the vicinity. It is emphasized that combined medical and industrial hygiene surveillance is more » essential for the safe management of such work operation, and workers engaged in such operations require proper respiratory equipment to minimize the risk of increased lead absorption. « less

Research paper thumbnail of Interactions between nutritional factors and drug biotransformations in man

Proceedings of the National Academy of Sciences of the United States of America, Jul 1, 1976

This study was undertaken to examine the influence of nutritional factors on the activity of the ... more This study was undertaken to examine the influence of nutritional factors on the activity of the mixed function oxidase system in man, which is cytochrome P450 dependent. Three normal volunteers were fed a low carbohydrate-high protein diet for 2 weeks, followed by a high carbohydrate-low protein diet for the following 2 weeks. At the end of each test diet period, the plasma elimination rates of antipyrine and theophylline were determined. The mean plasma half-life for antipyrine was 17.5 hr on the high carbohydrate-low protein diet and 9.2 hr on the low carbohydrate-high protein diet. The mean plasma half-life for theophylline was 8.9 hr on the high carbohydrate-low protein diet and 5.9 iwr on the low carbohydrate-high protein diet. These data demonstrate marked influences of dietary carbohydrate and/or protein ingestion on oxidative biotransformation of drugs in man. The effects of changes in dietary macronutrient composition on the hepatic microsomal enzymes that metabolize drugs, other foreign chemicals, and endogenous compounds, such as steroid hormones, have been studied extensively in animals (1). These studies show that dietary macronutrient composition, as well as the presence of contaminants and food additives, can influence the activities of these enzymes. Although dietary composition has been shown to be an important environmental determinant in the response of the experimental animal to pharmacological agents, such studies are lacking in man. A significant proportion of normal subjects manipulate their diets in weight-reducing regimens. Similarly, dietary treatments in clinical conditions, including obesity, atherosclerosis, and diabetes, are considered to play a significant role in the management of such disease problems. It is the purpose of these studies

Research paper thumbnail of Key terms and definitions in acute porphyrias: Results of an international Delphi consensus led by the European porphyria network

Journal of Inherited Metabolic Disease

Acute porphyrias are a group of rare inherited disorders causing acute neurovisceral attacks. Man... more Acute porphyrias are a group of rare inherited disorders causing acute neurovisceral attacks. Many terms used frequently in the literature and clinical practice are ambiguous, which can lead to confusion in the way patients are managed, studied, and reported in clinical studies. Agreed definitions are a necessary first step in developing management guidelines and will facilitate communication of results of future clinical research. The Delphi method was used to generate consensus on key terms and definitions in acute porphyria. The process started with a brainstorming phase offered to all members of the European Porphyria Network followed by two Delphi rounds among international experts in the field of porphyria (the Acute Porphyria Expert Panel). A consensus of 75% or more was defined as the agreement threshold. A total of 63 respondents from 26 countries participated in the brainstorming phase, leading to the choice of nine terms and definitions. A total of 34 experts were invited...

Research paper thumbnail of Light-Related Cutaneous Symptoms of Erythropoietic Protoporphyria and Associations With Light Sensitivity Measurements

JAMA Dermatology

ImportanceErythropoietic protoporphyria (EPP) is a rare and underdiagnosed genetic disease charac... more ImportanceErythropoietic protoporphyria (EPP) is a rare and underdiagnosed genetic disease characterized by painful sensitivity to light. A better understanding and characterization of its light-induced cutaneous symptoms may aid in the identification of EPP in patients.ObjectivesTo describe the cutaneous symptoms of erythropoietic protoporphyria (EPP) and to determine if these symptoms are associated with the degree of light sensitivity.Design, Setting, and ParticipantsThis was a cross-sectional study of adolescent and adult (≥15 years) patients with EPP across the US conducted by a single academic hospital via a remotely administered survey, measurements of light sensitivity by light dosimetry and by text message symptom assessments. Data analyses were conducted from November 2020 to April 2022.ExposuresSunlight exposure.Main Outcomes and MeasuresSelf-reported symptoms and association with measured light sensitivity.ResultsThe study sample consisted of 35 patients with EPP (mean [...

Research paper thumbnail of Prospective observational pilot study of quantitative light dosimetry in erythropoietic protoporphyria

Journal of the American Academy of Dermatology

Research paper thumbnail of Disorders of Haem Biosynthesis

Research paper thumbnail of Porphyrin Accumulation and Biliary Lithiasis Causing Diffusely Black Livers in Broiler Chickens

Research paper thumbnail of Dietary pectin and cellulose effects on hepatic and intestinal mixed-function oxidations and hepatic HMG-CoA reductase

Research paper thumbnail of Biochemical Diagnosis of Acute Hepatic Porphyria: Updated Expert Recommendations for Primary Care Physicians

The American Journal of the Medical Sciences, 2021

Acute hepatic porphyria (AHP) is a group of rare, metabolic diseases where patients can experienc... more Acute hepatic porphyria (AHP) is a group of rare, metabolic diseases where patients can experience acute neurovisceral attacks, chronic symptoms, and long-term complications. Diagnostic biochemical testing is widely available and effective, but a substantial time from symptom onset to diagnosis often delays treatment and increases morbidity. A panel of laboratory scientists and clinical AHP specialists collaborated to produce recommendations on how to enhance biochemical diagnosis of AHP in the USA. AHP should be considered in the differential diagnosis of unexplained abdominal pain, the most common symptom, soon after excluding common causes. Measurement of porphobilinogen (PBG) and porphyrins in a random urine sample, with results normalized to creatinine, is recommended as an effective and cost-efficient initial test for AHP. Delta-aminolevulinic acid testing may be included but is not essential. The optimal time to collect a urine sample is during an attack. Substantial PBG elevation confirms an AHP diagnosis and allows for prompt treatment initiation. Additional testing can determine AHP subtype and identify at-risk family members. Increased awareness of AHP and correct diagnostic methods will reduce diagnostic delay and improve patient outcomes.

Research paper thumbnail of Expanding Experience With Liver Transplantation in Acute Intermittent Porphyria

Liver Transplantation, 2021

Acute intermittent porphyria (AIP) is a rare autosomal dominant hepatic disease with potentially ... more Acute intermittent porphyria (AIP) is a rare autosomal dominant hepatic disease with potentially severe and potential fatal neurological manifestations. In the current issue, Lissing et. al. confirm that marked improvement can occur following liver transplantation(LT) (1). AIP results from heterozygous deficiency of the third of eight enzymes in the heme biosynthetic pathway. Attacks of neurovisceral symptoms occur when exacerbating factors upregulate the first and rate limiting enzyme of the pathway (5-aminolevulinic acid synthase 1 - ALAS1) in the liver, causing accumulation of the porphyrin precursors 5-aminolevulinic acid (ALA) and porphobilinogen (PBG).

Research paper thumbnail of A Phase 1/2 Open Label Extension Study of Givosiran, an Investigational Rnai Therapeutic, in Patients with Acute Intermittent Porphyria

Hematology, Transfusion and Cell Therapy, 2020

Background and Aims: Porto sinusoidal vascular liver disease (PSVD) represents a cause of presinu... more Background and Aims: Porto sinusoidal vascular liver disease (PSVD) represents a cause of presinusoidal portal hypertension which can often lead to formation of oesophageal or gastric varices and portal hypertension related bleeding. In cirrhotic patients, liver stiffness measurement by transient elastography (LSM) < 20 kPa and platelets (PLT) count >150.000 are able to rule-out high risk oesophageal varices. However, in patients PSVD there is no noninvasive test that can predict the presence of varices. We aimed to investigate whether LSM, spleen stiffness measurement (SSM) and PLT count have a role in prediction of varices in patients with PSVD. Method: Patients diagnosed with PSVD who were admitted at the RIGH 'Prof. dr. Octavian Fodor' and who had performed endoscopies prior to or at enrolment were included in the study. All patients had routine laboratory work out and performed liver and spleen measurements by transient elastography with a Fibroscan 502 Touch ® (M or XL probe). The median of 10 measurements with an IQR < 0.3 was considered adequate. A control group of cirrhotic of various etiologies compensated patients was also included in the study. Results: Nineteen patients with biopsy proven PSVD were included in the study. Mean age was 34.79 years [range 19-72] and included 57.9% of male patients. All patients were Child Pugh A and had a mean MELD score of 9.31 [range 6-17], mean PLT level was 120.000 [range 12.000-325.000]. Fifteen patients of the patients had varices, either esophageal (n = 11), gastric (n = 2) or both (n = 1). Mean LSM was 9.3 kPa [range 3-39.7] and mean SSM was 46.9 kPa [11.8-75]. The ratio between the difference of SSM and LSM and PLT count ((SSM-LSM)/ PLT) was the best test to predict the presence of varices with an AUROC of 0.83 CI 95% (0.64-1), p = 0.04. If the (SSM-LSM)/PLT ratio was <0.06, the test had a sensitivity of 100%, specificity of 25%, a PPV of 83% and a NPV of 100% with a +L = 1.33 and a-LR = 0 in prediction of varices. The test had a diagnostic accuracy of 84.2% (16 / 19). If the (SSM-LSM)/PLT ration was > = 0.29, the test had a sensitivity of 66%, specificity of 100%, a PPV of 100% and a NPV of 44% with a + L = infinite and a-LR = 0.33 in prediction of varices. When this ratio was tested in the cirrhotic population, the AUROC was 0.32 CI 95% (0.13-0.53), p = 0.13. Conclusion: The ratio of (SSM-LSM)/PLT has a high accuracy for predicting esophageal or gastric varices in patients with porto sinusoidal vascular liver disease, but not for patients with compensated cirrhosis. At a cutoff of 0.06, the test has a very large effect on ruling-out and at a cutoff of 0.29 the test has a very large effect on ruling-in the presence of varices in this disorder. In these patients, according to these cutoffs , endoscopies should be performed if the ratio is between 0.06 and 0.29. Due to small sample size and high prevalence of varices, these results need confirmation in a larger cohort.

Research paper thumbnail of Overall Health, Daily Functioning, and Quality of Life in Acute Hepatic Porphyria Patients: ENVISION, a Phase 3 Global, Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial

Digestive and Liver Disease, 2020

Research paper thumbnail of 996 Disease Characteristics of Acute Hepatic Porphyria Patients: ENVISION, a Phase 3 Global, Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial

American Journal of Gastroenterology, 2019

INTRODUCTION: Acute Hepatic Porphyria (AHP) is a family of rare genetic diseases due to enzyme de... more INTRODUCTION: Acute Hepatic Porphyria (AHP) is a family of rare genetic diseases due to enzyme deficiencies in heme biosynthesis in the liver that can lead to neurovisceral attacks and chronic symptoms. (1, 2) AHP is also associated with multiple long-term complications, including neuropathy (3,4), hypertension (5,6), chronic kidney disease (7), and hepatocellular carcinoma (8,9). METHODS: ENVISION (NCT03338816) was a Phase 3 global, multicenter, randomized, double-blind, placebo-controlled trial with an open label extension to evaluate the efficacy and safety of subcutaneous givosiran in AHP. Eligible patients had an AHP diagnosis and ≥2 attacks within the prior 6 months. At baseline detailed medical history and laboratory assessments were obtained. RESULTS: Ninety-four AHP patients enrolled, median (range) age 37.5 (19-65) years, 89% female, and median (range) of 6.5 (0.1–43) years since diagnosis. Patients had a median of 4 composite attacks in the preceding 6 months and 40% were...

Research paper thumbnail of 38 Prolongation of the Biochemical Effects and Clearance of Heme by Tin Mesoporphyrin in Acute Porphyria

Journal of Investigative Medicine, 2004

Research paper thumbnail of Disorders of Haem Biosynthesis

Inborn Metabolic Diseases, 2016

Research paper thumbnail of Lead intoxication: Effects on cytochrome P‐450‐mediated hepatic oxidations

Clinical Pharmacology & Therapeutics, 1976

Acute administration of lead to rats caused significant decreases in cytochrome P‐450, ethylmorph... more Acute administration of lead to rats caused significant decreases in cytochrome P‐450, ethylmorphine N‐demethylase, and aniline hydroxylase activities and prolonged hexobarbital‐induced sleeping times. However, chronic administration of lead to weanling rats caused no significant changes in hepatic cytochrome P‐450 levels or in the microsomal oxidative enzymes over a 12‐wk period. Eight patients exposed to lead in the process of burning through lead‐painted steel structures for at least 3 mo showed marked effects of chronic lead intoxication on the erythropoietic system: inhibition of erythrocyte δ‐aminolevulinic acid dehydratase, increased erythrocyte protoporphyrin levels, and increased urinary excretion of δ‐aminolevulinic acid. Chelation therapy greatly alleviated the inhibitory effects on dehydratase activity and decreased urinary δ‐aminolevulinic acid excretion. The plasma elimination rate of antipyrine, a drug primarily metabolized by hepatic microsomal enzymes, was determine...