The Experts below are selected from a list of 1323 Experts worldwide ranked by ideXlab platform

Irwin J. Goldstein - One of the best experts on this subject based on the ideXlab platform.

  • the fungal chimerolectin moa inhibits protein and dna synthesis in nih 3t3 cells and may induce bax mediated apoptosis
    Biochemical and Biophysical Research Communications, 2014
    Co-Authors: Gabriele Cordara, Ute Krengel, Harry C. Winter, Irwin J. Goldstein, Kirsten Sandvig
    Abstract:

    The Marasmius oreades mushroom agglutinin (MOA) is a blood group B-specific lectin carrying an active proteolytic domain. Its enzymatic activity has recently been shown to be critical for toxicity of MOA toward the fungivorous soil nematode Caenorhabditis elegans. Here we present evidence that MOA also induces cytotoxicity in a cellular model system (murine NIH/3T3 cells), by inhibiting protein synthesis, and that cytotoxicity correlates, at least in part, with proteolytic activity. A peptide-array screen identified the apoptosis mediator BAX as a potential proteolytic substrate and further suggests a variety of bacterial and fungal peptides as potential substrates. These findings are in line with the suggestion that MOA and related proteases may play a role for host defense.

  • comparison of the binding properties of the mushroom Marasmius oreades lectin and griffonia simplicifolia i b4 isolectin to αgalactosyl carbohydrate antigens in the surface phase
    Xenotransplantation, 2004
    Co-Authors: Svend Kirkeby, Harry C. Winter, Irwin J. Goldstein
    Abstract:

    Kirkeby S, Winter HC, Goldstein IJ. Comparison of the binding properties of the mushroom Marasmius oreades lectin and Griffonia simplicifolia I-B4 isolectin to agalactosyl carbohydrate antigens in the surface phase. Xenotransplantation 2004; 11: 254-261. � Blackwell Munksgaard, 2004 Abstract: The binding of two a-galactophilic lectins, Marasmius oreades agglutinin (MOA), and Griffonia simplicifolia I isolectin B4 (GS I-B4 )t o neoglycoproteins and natural glycoproteins were compared in a surface phase assay. Neoglycoproteins carrying various a-galactosylated glycans and laminin from basement membrane of mouse sarcoma that contains the xenogenic Gala1-3Gal1-4GlcNAc epitope were immobilized in microtiter plate wells and lectin binding determined with an enzyme- linked assay. After 24 h of incubation, MOA had higher affinity for the xenogenic pentasaccharide (Gala1-3Gal1-4GlcNAcb1-3Galb1-4Glc) than for the Gala-monosaccharide. The binding properties of MOA and GS I-B4 to the xenogenic disaccharide (Gala1-3Galb1) were comparable while the binding of MOA to the xenogenic pentasaccharide was much stronger than the binding of GS I-B4 to the same epitope. Non-xeno- genic disaccharide-coupled neoglycoproteins having galactose end groups linked a1-2 or a1-4 to Gal or linked a1-3 to GalNAc bound very weakly to MOA, whereas GS I-B4 recognized all of these disac- charides with similarly high affinity. MOA also showed high affinity for laminin. The results indicate that the Marasmius oreades lectin has nearly the same affinities as does GS I-B4 for the simple xenogenic carbohydrate antigens, but MOA has greater affinity for the pentasac- charide and is far more specific in its binding preferences than the Griffonia lectin.

  • comparison of the binding properties of the mushroom Marasmius oreades lectin and griffonia simplicifolia i b4 isolectin to αgalactosyl carbohydrate antigens in the surface phase
    Xenotransplantation, 2004
    Co-Authors: Svend Kirkeby, Harry C. Winter, Irwin J. Goldstein
    Abstract:

    The binding of two alpha-galactophilic lectins, Marasmius oreades agglutinin (MOA), and Griffonia simplicifolia I isolectin B(4) (GS I-B(4)) to neoglycoproteins and natural glycoproteins were compared in a surface phase assay. Neoglycoproteins carrying various alpha-galactosylated glycans and laminin from basement membrane of mouse sarcoma that contains the xenogenic Galalpha1-3Gal1-4GlcNAc epitope were immobilized in microtiter plate wells and lectin binding determined with an enzyme-linked assay. After 24 h of incubation, MOA had higher affinity for the xenogenic pentasaccharide (Galalpha1-3Gal1-4GlcNAcbeta1-3Galbeta1-4Glc) than for the Galalpha-monosaccharide. The binding properties of MOA and GS I-B(4) to the xenogenic disaccharide (Galalpha1-3Galbeta1) were comparable while the binding of MOA to the xenogenic pentasaccharide was much stronger than the binding of GS I-B(4) to the same epitope. Non-xenogenic disaccharide-coupled neoglycoproteins having galactose end groups linked alpha1-2 or alpha1-4 to Gal or linked alpha1-3 to GalNAc bound very weakly to MOA, whereas GS I-B(4) recognized all of these disaccharides with similarly high affinity. MOA also showed high affinity for laminin. The results indicate that the Marasmius oreades lectin has nearly the same affinities as does GS I-B(4) for the simple xenogenic carbohydrate antigens, but MOA has greater affinity for the pentasaccharide and is far more specific in its binding preferences than the Griffonia lectin.

Maitland K - One of the best experts on this subject based on the ideXlab platform.

  • Assessment of Myocardial Function in Kenyan Children With Severe, Acute Malnutrition: The Cardiac Physiology in Malnutrition (CAPMAL) Study
    'American Medical Association (AMA)', 2019
    Co-Authors: Brent B, Obonyo N, Akech S, Shebe M, Mpoya A, Mturi N, Berkley J, Tulloh R, Maitland K
    Abstract:

    Importance: Mortality among African children hospitalized with severe malnutrition remains high, with sudden, unexpected deaths leading to speculation about potential cardiac causes. Malnutrition is considered high risk for cardiac failure, but evidence is limited. Objective To investigate the role of cardiovascular dysfunction in African children with severe, acute malnutrition (SAM). Design, Setting, and Participants A prospective, matched case-control study, the Cardiac Physiology in Malnutrition (CAPMAL) study, of 88 children with SAM (exposed) vs 22 severity-matched patients without SAM (unexposed) was conducted between March 7, 2011, and February 20, 2012; data analysis was performed from October 1, 2012, to March 1, 2016. Exposures Echocardiographic and electrocardiographic (ECG) recordings (including 7-day Holter monitoring) at admission, day 7, and day 28. Main Outcomes and Measures Findings in children with (cases) and without (controls) SAM and in marasmus and kwashiorkor phenotypes were compared. Results Eighty-eight children (52 with marasmus and 36 with kwashiorkor) of the 418 admitted with SAM and 22 severity-matched controls were studied. A total of 63 children (57%) were boys; median age at admission was 19 months (range, 12-39 months). On admission, abnormalities more common in cases vs controls included severe hypokalemia (potassium 4.2 mU/L) (18 of 74 [24%] vs 1 of 21 [5%]) and were associated with typical electrocardiographic changes (T-wave inversion: odds ratio, 7.3; 95% CI, 1.9-28.0; P = .001), which corrected as potassium levels improved. Fourteen children with SAM (16%) but no controls died. Myocardial mass was lower in cases on admission but not by day 7. Results of the Tei Index, a measure of global cardiac function, were within the reference range and similar in cases (median, 0.37; interquartile range [IQR], 0.26-0.45) and controls (median, 0.36; IQR, 0.28-0.42). Echocardiography detected no evidence of cardiac failure among children with SAM, including those receiving intravenous fluids to correct hypovolemia. Cardiac dysfunction was generally associated with comorbidity and typical of hypovolemia, with low cardiac index (median, 4.9 L/min/m2; IQR, 3.9-6.1 L/min/m2), high systemic vascular resistance index (median, 1333 dyne seconds/cm5/m2; IQR, 1133-1752 dyne seconds/cm5/m2), and with few differences between the marasmus and kwashiorkor manifestations of malnutrition. Seven-day continuous ECG Holter monitoring during the high-risk initial refeeding period demonstrated self-limiting significant ventricular arrhythmias in 33 of 55 cases (60%) and 6 of 18 controls (33%) (P = .049); none were temporally related to adverse events, including fatalities. Conclusions and Relevance There is little evidence that African children with SAM are at greater risk of cardiac dysfunction or clinically significant arrhythmias than those without SAM or that marasmus and kwashiorkor differed in cardiovascular profile. These findings should prompt a review of current guidelines

  • Assessment of myocardial function in Kenyan children with severe, acute malnutrition
    'American Medical Association (AMA)', 2019
    Co-Authors: Brent B, Obonyo N, Akech S, Mpoya A, Mturi N, Shebbe M, Ja Berkley, Tulloh Rmr, Maitland K
    Abstract:

    Importance Mortality among African children hospitalized with severe malnutrition remains high, with sudden, unexpected deaths leading to speculation about potential cardiac causes. Malnutrition is considered high risk for cardiac failure, but evidence is limited. Objective To investigate the role of cardiovascular dysfunction in African children with severe, acute malnutrition (SAM). Design, Setting, and Participants A prospective, matched case-control study, the Cardiac Physiology in Malnutrition (CAPMAL) study, of 88 children with SAM (exposed) vs 22 severity-matched patients without SAM (unexposed) was conducted between March 7, 2011, and February 20, 2012; data analysis was performed from October 1, 2012, to March 1, 2016. Exposures Echocardiographic and electrocardiographic (ECG) recordings (including 7-day Holter monitoring) at admission, day 7, and day 28. Main Outcomes and Measures Findings in children with (cases) and without (controls) SAM and in marasmus and kwashiorkor phenotypes were compared. Results Eighty-eight children (52 with marasmus and 36 with kwashiorkor) of the 418 admitted with SAM and 22 severity-matched controls were studied. A total of 63 children (57%) were boys; median age at admission was 19 months (range, 12-39 months). On admission, abnormalities more common in cases vs controls included severe hypokalemia (potassium 4.2 mU/L) (18 of 74 [24%] vs 1 of 21 [5%]) and were associated with typical electrocardiographic changes (T-wave inversion: odds ratio, 7.3; 95% CI, 1.9-28.0; P = .001), which corrected as potassium levels improved. Fourteen children with SAM (16%) but no controls died. Myocardial mass was lower in cases on admission but not by day 7. Results of the Tei Index, a measure of global cardiac function, were within the reference range and similar in cases (median, 0.37; interquartile range [IQR], 0.26-0.45) and controls (median, 0.36; IQR, 0.28-0.42). Echocardiography detected no evidence of cardiac failure among children with SAM, including those receiving intravenous fluids to correct hypovolemia. Cardiac dysfunction was generally associated with comorbidity and typical of hypovolemia, with low cardiac index (median, 4.9 L/min/m2; IQR, 3.9-6.1 L/min/m2), high systemic vascular resistance index (median, 1333 dyne seconds/cm5/m2; IQR, 1133-1752 dyne seconds/cm5/m2), and with few differences between the marasmus and kwashiorkor manifestations of malnutrition. Seven-day continuous ECG Holter monitoring during the high-risk initial refeeding period demonstrated self-limiting significant ventricular arrhythmias in 33 of 55 cases (60%) and 6 of 18 controls (33%) (P = .049); none were temporally related to adverse events, including fatalities. Conclusions and Relevance There is little evidence that African children with SAM are at greater risk of cardiac dysfunction or clinically significant arrhythmias than those without SAM or that marasmus and kwashiorkor differed in cardiovascular profile. These findings should prompt a review of current guidelines

  • Assessment of Myocardial Function in Kenyan Children With Severe, Acute Malnutrition: The Cardiac Physiology in Malnutrition (CAPMAL) Study
    'American Medical Association (AMA)', 2019
    Co-Authors: Brent B, Obonyo N, Akech S, Shebe M, Mpoya A, Mturi N, Berkley J, Tulloh R, Maitland K
    Abstract:

    Importance: Mortality among African children hospitalized with severe malnutrition remains high, with sudden, unexpected deaths leading to speculation about potential cardiac causes. Malnutrition is considered high risk for cardiac failure, but evidence is limited. Objective To investigate the role of cardiovascular dysfunction in African children with severe, acute malnutrition (SAM). Design, Setting, and Participants A prospective, matched case-control study, the Cardiac Physiology in Malnutrition (CAPMAL) study, of 88 children with SAM (exposed) vs 22 severity-matched patients without SAM (unexposed) was conducted between March 7, 2011, and February 20, 2012; data analysis was performed from October 1, 2012, to March 1, 2016. Exposures Echocardiographic and electrocardiographic (ECG) recordings (including 7-day Holter monitoring) at admission, day 7, and day 28. Main Outcomes and Measures Findings in children with (cases) and without (controls) SAM and in marasmus and kwashiorkor phenotypes were compared. Results Eighty-eight children (52 with marasmus and 36 with kwashiorkor) of the 418 admitted with SAM and 22 severity-matched controls were studied. A total of 63 children (57%) were boys; median age at admission was 19 months (range, 12-39 months). On admission, abnormalities more common in cases vs controls included severe hypokalemia (potassium <2.5 mEq/L) (18 of 81 [22%] vs 0%), hypoalbuminemia (albumin level <3.4 g/dL) (66 of 88 [75%] vs 4 of 22 [18%]), and hypothyroidism (free thyroxine level <0.70 ng/dL or thyrotropin level >4.2 mU/L) (18 of 74 [24%] vs 1 of 21 [5%]) and were associated with typical electrocardiographic changes (T-wave inversion: odds ratio, 7.3; 95% CI, 1.9-28.0; P = .001), which corrected as potassium levels improved. Fourteen children with SAM (16%) but no controls died. Myocardial mass was lower in cases on admission but not by day 7. Results of the Tei Index, a measure of global cardiac function, were within the reference range and similar in cases (median, 0.37; interquartile range [IQR], 0.26-0.45) and controls (median, 0.36; IQR, 0.28-0.42). Echocardiography detected no evidence of cardiac failure among children with SAM, including those receiving intravenous fluids to correct hypovolemia. Cardiac dysfunction was generally associated with comorbidity and typical of hypovolemia, with low cardiac index (median, 4.9 L/min/m2; IQR, 3.9-6.1 L/min/m2), high systemic vascular resistance index (median, 1333 dyne seconds/cm5/m2; IQR, 1133-1752 dyne seconds/cm5/m2), and with few differences between the marasmus and kwashiorkor manifestations of malnutrition. Seven-day continuous ECG Holter monitoring during the high-risk initial refeeding period demonstrated self-limiting significant ventricular arrhythmias in 33 of 55 cases (60%) and 6 of 18 controls (33%) (P = .049); none were temporally related to adverse events, including fatalities. Conclusions and Relevance There is little evidence that African children with SAM are at greater risk of cardiac dysfunction or clinically significant arrhythmias than those without SAM or that marasmus and kwashiorkor differed in cardiovascular profile. These findings should prompt a review of current guidelines

Svend Kirkeby - One of the best experts on this subject based on the ideXlab platform.

  • comparison of the binding properties of the mushroom Marasmius oreades lectin and griffonia simplicifolia i b4 isolectin to αgalactosyl carbohydrate antigens in the surface phase
    Xenotransplantation, 2004
    Co-Authors: Svend Kirkeby, Harry C. Winter, Irwin J. Goldstein
    Abstract:

    Kirkeby S, Winter HC, Goldstein IJ. Comparison of the binding properties of the mushroom Marasmius oreades lectin and Griffonia simplicifolia I-B4 isolectin to agalactosyl carbohydrate antigens in the surface phase. Xenotransplantation 2004; 11: 254-261. � Blackwell Munksgaard, 2004 Abstract: The binding of two a-galactophilic lectins, Marasmius oreades agglutinin (MOA), and Griffonia simplicifolia I isolectin B4 (GS I-B4 )t o neoglycoproteins and natural glycoproteins were compared in a surface phase assay. Neoglycoproteins carrying various a-galactosylated glycans and laminin from basement membrane of mouse sarcoma that contains the xenogenic Gala1-3Gal1-4GlcNAc epitope were immobilized in microtiter plate wells and lectin binding determined with an enzyme- linked assay. After 24 h of incubation, MOA had higher affinity for the xenogenic pentasaccharide (Gala1-3Gal1-4GlcNAcb1-3Galb1-4Glc) than for the Gala-monosaccharide. The binding properties of MOA and GS I-B4 to the xenogenic disaccharide (Gala1-3Galb1) were comparable while the binding of MOA to the xenogenic pentasaccharide was much stronger than the binding of GS I-B4 to the same epitope. Non-xeno- genic disaccharide-coupled neoglycoproteins having galactose end groups linked a1-2 or a1-4 to Gal or linked a1-3 to GalNAc bound very weakly to MOA, whereas GS I-B4 recognized all of these disac- charides with similarly high affinity. MOA also showed high affinity for laminin. The results indicate that the Marasmius oreades lectin has nearly the same affinities as does GS I-B4 for the simple xenogenic carbohydrate antigens, but MOA has greater affinity for the pentasac- charide and is far more specific in its binding preferences than the Griffonia lectin.

  • comparison of the binding properties of the mushroom Marasmius oreades lectin and griffonia simplicifolia i b4 isolectin to αgalactosyl carbohydrate antigens in the surface phase
    Xenotransplantation, 2004
    Co-Authors: Svend Kirkeby, Harry C. Winter, Irwin J. Goldstein
    Abstract:

    The binding of two alpha-galactophilic lectins, Marasmius oreades agglutinin (MOA), and Griffonia simplicifolia I isolectin B(4) (GS I-B(4)) to neoglycoproteins and natural glycoproteins were compared in a surface phase assay. Neoglycoproteins carrying various alpha-galactosylated glycans and laminin from basement membrane of mouse sarcoma that contains the xenogenic Galalpha1-3Gal1-4GlcNAc epitope were immobilized in microtiter plate wells and lectin binding determined with an enzyme-linked assay. After 24 h of incubation, MOA had higher affinity for the xenogenic pentasaccharide (Galalpha1-3Gal1-4GlcNAcbeta1-3Galbeta1-4Glc) than for the Galalpha-monosaccharide. The binding properties of MOA and GS I-B(4) to the xenogenic disaccharide (Galalpha1-3Galbeta1) were comparable while the binding of MOA to the xenogenic pentasaccharide was much stronger than the binding of GS I-B(4) to the same epitope. Non-xenogenic disaccharide-coupled neoglycoproteins having galactose end groups linked alpha1-2 or alpha1-4 to Gal or linked alpha1-3 to GalNAc bound very weakly to MOA, whereas GS I-B(4) recognized all of these disaccharides with similarly high affinity. MOA also showed high affinity for laminin. The results indicate that the Marasmius oreades lectin has nearly the same affinities as does GS I-B(4) for the simple xenogenic carbohydrate antigens, but MOA has greater affinity for the pentasaccharide and is far more specific in its binding preferences than the Griffonia lectin.

Harry C. Winter - One of the best experts on this subject based on the ideXlab platform.

  • the fungal chimerolectin moa inhibits protein and dna synthesis in nih 3t3 cells and may induce bax mediated apoptosis
    Biochemical and Biophysical Research Communications, 2014
    Co-Authors: Gabriele Cordara, Ute Krengel, Harry C. Winter, Irwin J. Goldstein, Kirsten Sandvig
    Abstract:

    The Marasmius oreades mushroom agglutinin (MOA) is a blood group B-specific lectin carrying an active proteolytic domain. Its enzymatic activity has recently been shown to be critical for toxicity of MOA toward the fungivorous soil nematode Caenorhabditis elegans. Here we present evidence that MOA also induces cytotoxicity in a cellular model system (murine NIH/3T3 cells), by inhibiting protein synthesis, and that cytotoxicity correlates, at least in part, with proteolytic activity. A peptide-array screen identified the apoptosis mediator BAX as a potential proteolytic substrate and further suggests a variety of bacterial and fungal peptides as potential substrates. These findings are in line with the suggestion that MOA and related proteases may play a role for host defense.

  • comparison of the binding properties of the mushroom Marasmius oreades lectin and griffonia simplicifolia i b4 isolectin to αgalactosyl carbohydrate antigens in the surface phase
    Xenotransplantation, 2004
    Co-Authors: Svend Kirkeby, Harry C. Winter, Irwin J. Goldstein
    Abstract:

    Kirkeby S, Winter HC, Goldstein IJ. Comparison of the binding properties of the mushroom Marasmius oreades lectin and Griffonia simplicifolia I-B4 isolectin to agalactosyl carbohydrate antigens in the surface phase. Xenotransplantation 2004; 11: 254-261. � Blackwell Munksgaard, 2004 Abstract: The binding of two a-galactophilic lectins, Marasmius oreades agglutinin (MOA), and Griffonia simplicifolia I isolectin B4 (GS I-B4 )t o neoglycoproteins and natural glycoproteins were compared in a surface phase assay. Neoglycoproteins carrying various a-galactosylated glycans and laminin from basement membrane of mouse sarcoma that contains the xenogenic Gala1-3Gal1-4GlcNAc epitope were immobilized in microtiter plate wells and lectin binding determined with an enzyme- linked assay. After 24 h of incubation, MOA had higher affinity for the xenogenic pentasaccharide (Gala1-3Gal1-4GlcNAcb1-3Galb1-4Glc) than for the Gala-monosaccharide. The binding properties of MOA and GS I-B4 to the xenogenic disaccharide (Gala1-3Galb1) were comparable while the binding of MOA to the xenogenic pentasaccharide was much stronger than the binding of GS I-B4 to the same epitope. Non-xeno- genic disaccharide-coupled neoglycoproteins having galactose end groups linked a1-2 or a1-4 to Gal or linked a1-3 to GalNAc bound very weakly to MOA, whereas GS I-B4 recognized all of these disac- charides with similarly high affinity. MOA also showed high affinity for laminin. The results indicate that the Marasmius oreades lectin has nearly the same affinities as does GS I-B4 for the simple xenogenic carbohydrate antigens, but MOA has greater affinity for the pentasac- charide and is far more specific in its binding preferences than the Griffonia lectin.

  • comparison of the binding properties of the mushroom Marasmius oreades lectin and griffonia simplicifolia i b4 isolectin to αgalactosyl carbohydrate antigens in the surface phase
    Xenotransplantation, 2004
    Co-Authors: Svend Kirkeby, Harry C. Winter, Irwin J. Goldstein
    Abstract:

    The binding of two alpha-galactophilic lectins, Marasmius oreades agglutinin (MOA), and Griffonia simplicifolia I isolectin B(4) (GS I-B(4)) to neoglycoproteins and natural glycoproteins were compared in a surface phase assay. Neoglycoproteins carrying various alpha-galactosylated glycans and laminin from basement membrane of mouse sarcoma that contains the xenogenic Galalpha1-3Gal1-4GlcNAc epitope were immobilized in microtiter plate wells and lectin binding determined with an enzyme-linked assay. After 24 h of incubation, MOA had higher affinity for the xenogenic pentasaccharide (Galalpha1-3Gal1-4GlcNAcbeta1-3Galbeta1-4Glc) than for the Galalpha-monosaccharide. The binding properties of MOA and GS I-B(4) to the xenogenic disaccharide (Galalpha1-3Galbeta1) were comparable while the binding of MOA to the xenogenic pentasaccharide was much stronger than the binding of GS I-B(4) to the same epitope. Non-xenogenic disaccharide-coupled neoglycoproteins having galactose end groups linked alpha1-2 or alpha1-4 to Gal or linked alpha1-3 to GalNAc bound very weakly to MOA, whereas GS I-B(4) recognized all of these disaccharides with similarly high affinity. MOA also showed high affinity for laminin. The results indicate that the Marasmius oreades lectin has nearly the same affinities as does GS I-B(4) for the simple xenogenic carbohydrate antigens, but MOA has greater affinity for the pentasaccharide and is far more specific in its binding preferences than the Griffonia lectin.

Brent B - One of the best experts on this subject based on the ideXlab platform.

  • Assessment of Myocardial Function in Kenyan Children With Severe, Acute Malnutrition: The Cardiac Physiology in Malnutrition (CAPMAL) Study
    'American Medical Association (AMA)', 2019
    Co-Authors: Brent B, Obonyo N, Akech S, Shebe M, Mpoya A, Mturi N, Berkley J, Tulloh R, Maitland K
    Abstract:

    Importance: Mortality among African children hospitalized with severe malnutrition remains high, with sudden, unexpected deaths leading to speculation about potential cardiac causes. Malnutrition is considered high risk for cardiac failure, but evidence is limited. Objective To investigate the role of cardiovascular dysfunction in African children with severe, acute malnutrition (SAM). Design, Setting, and Participants A prospective, matched case-control study, the Cardiac Physiology in Malnutrition (CAPMAL) study, of 88 children with SAM (exposed) vs 22 severity-matched patients without SAM (unexposed) was conducted between March 7, 2011, and February 20, 2012; data analysis was performed from October 1, 2012, to March 1, 2016. Exposures Echocardiographic and electrocardiographic (ECG) recordings (including 7-day Holter monitoring) at admission, day 7, and day 28. Main Outcomes and Measures Findings in children with (cases) and without (controls) SAM and in marasmus and kwashiorkor phenotypes were compared. Results Eighty-eight children (52 with marasmus and 36 with kwashiorkor) of the 418 admitted with SAM and 22 severity-matched controls were studied. A total of 63 children (57%) were boys; median age at admission was 19 months (range, 12-39 months). On admission, abnormalities more common in cases vs controls included severe hypokalemia (potassium 4.2 mU/L) (18 of 74 [24%] vs 1 of 21 [5%]) and were associated with typical electrocardiographic changes (T-wave inversion: odds ratio, 7.3; 95% CI, 1.9-28.0; P = .001), which corrected as potassium levels improved. Fourteen children with SAM (16%) but no controls died. Myocardial mass was lower in cases on admission but not by day 7. Results of the Tei Index, a measure of global cardiac function, were within the reference range and similar in cases (median, 0.37; interquartile range [IQR], 0.26-0.45) and controls (median, 0.36; IQR, 0.28-0.42). Echocardiography detected no evidence of cardiac failure among children with SAM, including those receiving intravenous fluids to correct hypovolemia. Cardiac dysfunction was generally associated with comorbidity and typical of hypovolemia, with low cardiac index (median, 4.9 L/min/m2; IQR, 3.9-6.1 L/min/m2), high systemic vascular resistance index (median, 1333 dyne seconds/cm5/m2; IQR, 1133-1752 dyne seconds/cm5/m2), and with few differences between the marasmus and kwashiorkor manifestations of malnutrition. Seven-day continuous ECG Holter monitoring during the high-risk initial refeeding period demonstrated self-limiting significant ventricular arrhythmias in 33 of 55 cases (60%) and 6 of 18 controls (33%) (P = .049); none were temporally related to adverse events, including fatalities. Conclusions and Relevance There is little evidence that African children with SAM are at greater risk of cardiac dysfunction or clinically significant arrhythmias than those without SAM or that marasmus and kwashiorkor differed in cardiovascular profile. These findings should prompt a review of current guidelines

  • Assessment of myocardial function in Kenyan children with severe, acute malnutrition
    'American Medical Association (AMA)', 2019
    Co-Authors: Brent B, Obonyo N, Akech S, Mpoya A, Mturi N, Shebbe M, Ja Berkley, Tulloh Rmr, Maitland K
    Abstract:

    Importance Mortality among African children hospitalized with severe malnutrition remains high, with sudden, unexpected deaths leading to speculation about potential cardiac causes. Malnutrition is considered high risk for cardiac failure, but evidence is limited. Objective To investigate the role of cardiovascular dysfunction in African children with severe, acute malnutrition (SAM). Design, Setting, and Participants A prospective, matched case-control study, the Cardiac Physiology in Malnutrition (CAPMAL) study, of 88 children with SAM (exposed) vs 22 severity-matched patients without SAM (unexposed) was conducted between March 7, 2011, and February 20, 2012; data analysis was performed from October 1, 2012, to March 1, 2016. Exposures Echocardiographic and electrocardiographic (ECG) recordings (including 7-day Holter monitoring) at admission, day 7, and day 28. Main Outcomes and Measures Findings in children with (cases) and without (controls) SAM and in marasmus and kwashiorkor phenotypes were compared. Results Eighty-eight children (52 with marasmus and 36 with kwashiorkor) of the 418 admitted with SAM and 22 severity-matched controls were studied. A total of 63 children (57%) were boys; median age at admission was 19 months (range, 12-39 months). On admission, abnormalities more common in cases vs controls included severe hypokalemia (potassium 4.2 mU/L) (18 of 74 [24%] vs 1 of 21 [5%]) and were associated with typical electrocardiographic changes (T-wave inversion: odds ratio, 7.3; 95% CI, 1.9-28.0; P = .001), which corrected as potassium levels improved. Fourteen children with SAM (16%) but no controls died. Myocardial mass was lower in cases on admission but not by day 7. Results of the Tei Index, a measure of global cardiac function, were within the reference range and similar in cases (median, 0.37; interquartile range [IQR], 0.26-0.45) and controls (median, 0.36; IQR, 0.28-0.42). Echocardiography detected no evidence of cardiac failure among children with SAM, including those receiving intravenous fluids to correct hypovolemia. Cardiac dysfunction was generally associated with comorbidity and typical of hypovolemia, with low cardiac index (median, 4.9 L/min/m2; IQR, 3.9-6.1 L/min/m2), high systemic vascular resistance index (median, 1333 dyne seconds/cm5/m2; IQR, 1133-1752 dyne seconds/cm5/m2), and with few differences between the marasmus and kwashiorkor manifestations of malnutrition. Seven-day continuous ECG Holter monitoring during the high-risk initial refeeding period demonstrated self-limiting significant ventricular arrhythmias in 33 of 55 cases (60%) and 6 of 18 controls (33%) (P = .049); none were temporally related to adverse events, including fatalities. Conclusions and Relevance There is little evidence that African children with SAM are at greater risk of cardiac dysfunction or clinically significant arrhythmias than those without SAM or that marasmus and kwashiorkor differed in cardiovascular profile. These findings should prompt a review of current guidelines

  • Assessment of Myocardial Function in Kenyan Children With Severe, Acute Malnutrition: The Cardiac Physiology in Malnutrition (CAPMAL) Study
    'American Medical Association (AMA)', 2019
    Co-Authors: Brent B, Obonyo N, Akech S, Shebe M, Mpoya A, Mturi N, Berkley J, Tulloh R, Maitland K
    Abstract:

    Importance: Mortality among African children hospitalized with severe malnutrition remains high, with sudden, unexpected deaths leading to speculation about potential cardiac causes. Malnutrition is considered high risk for cardiac failure, but evidence is limited. Objective To investigate the role of cardiovascular dysfunction in African children with severe, acute malnutrition (SAM). Design, Setting, and Participants A prospective, matched case-control study, the Cardiac Physiology in Malnutrition (CAPMAL) study, of 88 children with SAM (exposed) vs 22 severity-matched patients without SAM (unexposed) was conducted between March 7, 2011, and February 20, 2012; data analysis was performed from October 1, 2012, to March 1, 2016. Exposures Echocardiographic and electrocardiographic (ECG) recordings (including 7-day Holter monitoring) at admission, day 7, and day 28. Main Outcomes and Measures Findings in children with (cases) and without (controls) SAM and in marasmus and kwashiorkor phenotypes were compared. Results Eighty-eight children (52 with marasmus and 36 with kwashiorkor) of the 418 admitted with SAM and 22 severity-matched controls were studied. A total of 63 children (57%) were boys; median age at admission was 19 months (range, 12-39 months). On admission, abnormalities more common in cases vs controls included severe hypokalemia (potassium <2.5 mEq/L) (18 of 81 [22%] vs 0%), hypoalbuminemia (albumin level <3.4 g/dL) (66 of 88 [75%] vs 4 of 22 [18%]), and hypothyroidism (free thyroxine level <0.70 ng/dL or thyrotropin level >4.2 mU/L) (18 of 74 [24%] vs 1 of 21 [5%]) and were associated with typical electrocardiographic changes (T-wave inversion: odds ratio, 7.3; 95% CI, 1.9-28.0; P = .001), which corrected as potassium levels improved. Fourteen children with SAM (16%) but no controls died. Myocardial mass was lower in cases on admission but not by day 7. Results of the Tei Index, a measure of global cardiac function, were within the reference range and similar in cases (median, 0.37; interquartile range [IQR], 0.26-0.45) and controls (median, 0.36; IQR, 0.28-0.42). Echocardiography detected no evidence of cardiac failure among children with SAM, including those receiving intravenous fluids to correct hypovolemia. Cardiac dysfunction was generally associated with comorbidity and typical of hypovolemia, with low cardiac index (median, 4.9 L/min/m2; IQR, 3.9-6.1 L/min/m2), high systemic vascular resistance index (median, 1333 dyne seconds/cm5/m2; IQR, 1133-1752 dyne seconds/cm5/m2), and with few differences between the marasmus and kwashiorkor manifestations of malnutrition. Seven-day continuous ECG Holter monitoring during the high-risk initial refeeding period demonstrated self-limiting significant ventricular arrhythmias in 33 of 55 cases (60%) and 6 of 18 controls (33%) (P = .049); none were temporally related to adverse events, including fatalities. Conclusions and Relevance There is little evidence that African children with SAM are at greater risk of cardiac dysfunction or clinically significant arrhythmias than those without SAM or that marasmus and kwashiorkor differed in cardiovascular profile. These findings should prompt a review of current guidelines