RESUMO
BACKGROUND: Severe acute malnutrition in childhood manifests as oedematous (kwashiorkor, marasmic kwashiorkor) and non-oedematous (marasmus) syndromes with very different prognoses. Kwashiorkor differs from marasmus in the patterns of protein, amino acid and lipid metabolism when patients are acutely ill as well as after rehabilitation to ideal weight for height. Metabolic patterns among marasmic patients define them as metabolically thrifty, while kwashiorkor patients function as metabolically profligate. Such differences might underlie syndromic presentation and prognosis. However, no fundamental explanation exists for these differences in metabolism, nor clinical pictures, given similar exposures to undernutrition. We hypothesized that different developmental trajectories underlie these clinical-metabolic phenotypes: if so this would be strong evidence in support of predictive adaptation model of developmental plasticity. METHODOLOGY/PRINCIPAL FINDINGS: We reviewed the records of all children admitted with severe acute malnutrition to the Tropical Metabolism Research Unit Ward of the University Hospital of the West Indies, Kingston, Jamaica during 1962-1992. We used Wellcome criteria to establish the diagnoses of kwashiorkor (n = 391), marasmus (n = 383), and marasmic-kwashiorkor (n = 375). We recorded participants' birth weights, as determined from maternal recall at the time of admission. Those who developed kwashiorkor had 333 g (95% confidence interval 217 to 449, p<0.001) higher mean birthweight than those who developed marasmus. CONCLUSIONS/SIGNIFICANCE: These data are consistent with a model suggesting that plastic mechanisms operative in utero induce potential marasmics to develop with a metabolic physiology more able to adapt to postnatal undernutrition than those of higher birthweight. Given the different mortality risks of these different syndromes, this observation is supportive of the predictive adaptive response hypothesis and is the first empirical demonstration of the advantageous effects of such a response in humans. The study has implications for understanding pathways to obesity and its cardio-metabolic co-morbidities in poor countries and for famine intervention programs.
Assuntos
Adaptação Fisiológica , Kwashiorkor/diagnóstico , Kwashiorkor/epidemiologia , Modelos Biológicos , Diagnóstico Pré-Natal , Peso ao Nascer , Feminino , Humanos , Lactente , Jamaica/epidemiologia , Kwashiorkor/mortalidade , Masculino , Análise de SobrevidaRESUMO
OBJECTIVE: To quantify intestinal glucose absorption in children with two types of severe malnutrition, kwashiorkor and marasmus, compared with healthy children. STUDY DESIGN: Children with kwashiorkor (n = 6) and marasmus (n = 9) and control subjects (n = 3) received a primed (13 mg/kg), constant infusion (0.15 mg/kg/min) of [6,6H2]glucose for 4.5 hours. Two hours after start of the infusion an oral bolus of glucose 1.75 g/kg labeled with [U-13C]glucose 10 mg/g was given and was followed by periodic blood sampling. Mathematical modeling was applied to determine oral glucose absorption. RESULTS: Median total glucose absorption was 5.9 mmol/kg, interquartile range (IQR) 4.5-6.7 mmol/kg and 4.4 (IQR 2.9-5.9) mmol/kg in children with kwashiorkor and marasmus compared with 7.7 (IQR 5.8-9.0) mmol/kg in control subjects; P = .03 compared with marasmus). Children with the lowest glucose absorption were found specifically in the kwashiorkor group and marasmic children with hypoalbuminemia. Severe impairment in absorption correlated with urinary 8-hydroxydeoxyguanosine secretion (r = -0.62, P = .01). CONCLUSIONS: Severe malnutrition is associated with an impaired glucose absorption and decreased glucose absorption correlates with oxidative stress in these children.
Assuntos
Glicemia/metabolismo , Glucose/administração & dosagem , Absorção Intestinal , Desnutrição/diagnóstico , Desnutrição/mortalidade , Estudos de Casos e Controles , Criança , Pré-Escolar , Países em Desenvolvimento , Feminino , Gluconeogênese/fisiologia , Glucose/farmacocinética , Humanos , Lactente , Infusões Intravenosas , Kwashiorkor/sangue , Kwashiorkor/diagnóstico , Kwashiorkor/mortalidade , Malaui , Masculino , Desnutrição/sangue , Estresse Oxidativo/fisiologia , Desnutrição Proteico-Calórica/sangue , Desnutrição Proteico-Calórica/diagnóstico , Desnutrição Proteico-Calórica/mortalidade , Valores de Referência , Medição de Risco , Índice de Gravidade de Doença , Estatísticas não Paramétricas , Taxa de SobrevidaRESUMO
Severe hypophosphatemia, serum phosphate concentration <0.32 mmol/L (<1.0 mg/dL), occurred in 8 of 68 (12%) of children with kwashiorkor within 48 hours of admission; 5 of 8 (63%) of these children died, compared with 13 of 60 (22%) children without severe hypophosphatemia (P <.02). Dermatosis and dehydration were significantly correlated with severe hypophosphatemia, but these clinical signs could not reliably predict fatal cases. Severe hypophosphatemia seems to be common and life-threatening in children with kwashiorkor in Malawi.
PIP: Severe hypophosphatemia, serum inorganic phosphate concentration of less than 0.32 mmol/l, is associated with leukocyte dysfunction, acute respiratory decompensation, cardiac arrhythmias, and heart failure. The condition has been described in children with kwashiorkor from South Africa, but not in children from Jamaica or India. In acute kwashiorkor in sub-Saharan Africa, the case fatality rate remains high, often over 20%, despite the implementation of standard treatment protocols. The authors examined whether severe hypophosphatemia was frequent at presentation or during initial refeeding among Malawian children with kwashiorkor and whether it was associated with a fatal outcome. All children under age 10 years who presented with kwashiorkor to the Queen Elizabeth Central Hospital in Blantyre during a 2-month period were eligible and enrolled in the study. 68 children with kwashiorkor were studied. Severe hypophosphatemia occurred in 8 (12%) children with kwashiorkor within 48 hours of admission. 5 of these 8 (63%) children died, compared with 13 of 60 (22%) children without severe hypophosphatemia. Dermatosis and dehydration were significantly correlated with severe hypophosphatemia, but these clinical signs could not reliably predict fatal cases. Severe hypophosphatemia appears to be common and life-threatening in children with kwashiorkor in Malawi.
Assuntos
Hipofosfatemia/complicações , Hipofosfatemia/mortalidade , Kwashiorkor/complicações , Kwashiorkor/mortalidade , Pré-Escolar , Humanos , Lactente , Malaui/epidemiologia , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
The case fatality ratio (CFR) in acute protein-energy malnutrition (PEM) achieved in the Tropical Metabolism Research Unit (TMRU) was compared with that of other tertiary care facilities in Kingston. Trends in admission and fatality rates, case severity and complications were also examined. From ward admission registers for Bustamante Hospital for Children (BHC), the University Hospital of the West Indies (UHWI), children's wards and the TMRU all cases of PEM admitted from 1982 through 1991 were enumerated and there was a docket search for random subsamples. Ten-year mean CFR percent for BHC was 8.8 (n=1974); for UHWI wards 5.5 (n=658); for TMRU 7.1 (n=662). BHC has the least restrictions on admission and showed most clearly that the peak time in Kingston for admission of PEM was around 1985, falling to a minimum in 1988 - 1990 and rising again in 1991; however, the other sites also showed similar trends. BHC had a range of CFR precent p.a. of 20.0 to 3.0, with a striking fall in the second half of the decade. There was no temporal CFR trend for the UHWI or TMRU. The latter institution had the highest proportion of admissions with marasmic-kwashiorkor and the lowest proportion with recorded infection. The annual variation in numbers of PEM deaths at BHC was best accounted for by (a) percentage change in consumer price index and (b) percentage change in the US$ value of the Jamaican $, in the preceding year, and (c) annual number of admissions, together. Generally, our findings suggest a minor role for expert in-patient management in reducing deaths from PEM
Assuntos
Feminino , Humanos , Lactente , Recém-Nascido , Pré-Escolar , Kwashiorkor/mortalidade , Desnutrição Proteico-Calórica/mortalidade , Fatores Socioeconômicos , Kwashiorkor/economia , Análise de Regressão , Mortalidade Hospitalar/tendências , Desnutrição Proteico-Calórica/economia , Inflação , JamaicaRESUMO
The case fatality ratio (CFR) in acute protein-energy malnutrition (PEM) achieved in the Tropical Metabolism Research Unit (TMRU) was compared with that of other tertiary care facilities in Kingston. Trends in admission and fatality rates, case severity and complications were also examined. From ward admission registers for Bustamante Hospital for Children (BHC), the University Hospital of the West Indies (UHWI), children's wards and the TMRU all cases of PEM admitted from 1982 through 1991 were enumerated and there was a docket search for random subsamples. Ten-year mean CFR percent for BHC was 8.8 (n=1974); for UHWI wards 5.5 (n=658); for TMRU 7.1 (n=662). BHC has the least restrictions on admission and showed most clearly that the peak time in Kingston for admission of PEM was around 1985, falling to a minimum in 1988 - 1990 and rising again in 1991; however, the other sites also showed similar trends. BHC had a range of CFR precent p.a. of 20.0 to 3.0, with a striking fall in the second half of the decade. There was no temporal CFR trend for the UHWI or TMRU. The latter institution had the highest proportion of admissions with marasmic-kwashiorkor and the lowest proportion with recorded infection. The annual variation in numbers of PEM deaths at BHC was best accounted for by (a) percentage change in consumer price index and (b) percentage change in the US$ value of the Jamaican $, in the preceding year, and (c) annual number of admissions, together. Generally, our findings suggest a minor role for expert in-patient management in reducing deaths from PEM (AU)
Assuntos
Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pré-Escolar , Estudo Comparativo , Desnutrição Proteico-Calórica/mortalidade , Kwashiorkor/mortalidade , Desnutrição Proteico-Calórica/economia , Kwashiorkor/economia , Mortalidade Hospitalar/tendências , Fatores Socioeconômicos , Jamaica , Análise de Regressão , InflaçãoRESUMO
Glutathione S-transferases (GSTs) are principally involved in detoxification. These enzymes can be induced by an increased flux of substrate, such as occurs during pro-oxidative stress or antioxidant deficiency. We tested the hypothesis that the postulated oxidative stress in severe malnutrition would result in induction of GSTs in erythrocytes. Erythrocyte GST activity towards 1-chloro-2,4-dinitrobenzene (CDNB) was measured in 271 malnourished children (22 undernourished; 92 marasmic; 82 kwashiorkor; 75 marasmic-kwashiorkor) and 48 healthy children. GST activity in the malnourished children was significantly higher than the control group (P < 0.01). The GST activity in the four classes of malnutrition did not differ. There was a weak relationship between GST activity and the height deficit, but not with the weight deficit, or the clinical features displayed by the children. The 11 children that died had a higher value than the survivors. There was no change in GST with anthropometric recovery. We conclude that erythrocyte GST has been induced in children with malnutrition. Induction of erythrocyte GST may be the result of exposure of the children to oxidative stress during the months prior to their presentation with severe malnutrition.
Assuntos
Transtornos da Nutrição Infantil/enzimologia , Eritrócitos/enzimologia , Glutationa Transferase/metabolismo , Kwashiorkor/enzimologia , Desnutrição Proteico-Calórica/enzimologia , Fatores Etários , Estatura , Peso Corporal , Estudos de Casos e Controles , Transtornos da Nutrição Infantil/sangue , Transtornos da Nutrição Infantil/classificação , Transtornos da Nutrição Infantil/mortalidade , Pré-Escolar , Doença Crônica , Eritrócitos/química , Glutationa Transferase/análise , Glutationa Transferase/fisiologia , Humanos , Lactente , Kwashiorkor/sangue , Kwashiorkor/classificação , Kwashiorkor/mortalidade , Oxidantes/efeitos adversos , Admissão do Paciente , Alta do Paciente , Desnutrição Proteico-Calórica/sangue , Desnutrição Proteico-Calórica/classificação , Desnutrição Proteico-Calórica/mortalidade , Índice de Gravidade de Doença , Estresse Fisiológico/induzido quimicamente , Taxa de SobrevidaRESUMO
Glutathione S-transferases (GSTs) are principally involved in detoxication. These enzymes can be induced by an increased flux of substrate, such as occurs during pro-oxidative stress or antioxidant deficiency. We tested the hypothesis that the postulated oxidative stress in severe malnutrition would result in induction of GSTs in erythocytes. Erythrocyte GST activity towards 1-chloro-2, 4-dinitrobenzene (CDNB) was measured in 271 malnourished children (22 undernourished; 92 marasmic; 82 kwashiorkor; 75 marasmic-kwashiorkor) and 48 healthy children. GST activity in the malnourished children was significnatly higher than the control group (p < 0.01). The GST activity in the four classes of malnutrition did not differ. There was a weak relationship between GST activity and the height deficit, but not with the weight deficit, or the clinical features displayed by the children. The 11 children that died had a higher value than the survivors. There was no change in GST with anthropometric recovery. We conclude that erythrocyte GST has been induced in children with malnutrition. Induction of erythrocyte GST may be the result of exposure of the children to oxidative stress during the months prior to their presentation with severe malnutrition (AU)
Assuntos
Humanos , Lactente , Pré-Escolar , Transtornos da Nutrição Infantil/enzimologia , Eritrócitos/enzimologia , Desnutrição Proteico-Calórica/enzimologia , Glutationa Transferase/metabolismo , Kwashiorkor/enzimologia , Fatores Etários , Estatura , Peso Corporal , Estudos de Casos e Controles , Transtornos da Nutrição Infantil/sangue , Transtornos da Nutrição Infantil/classificação , Transtornos da Nutrição Infantil/mortalidade , Doença Crônica , Eritrócitos , Química , Glutationa Transferase/análise , Glutationa Transferase/fisiologia , Kwashiorkor/sangue , Kwashiorkor/classificação , Kwashiorkor/mortalidade , Oxidantes Fotoquímicos/efeitos adversos , Admissão do Paciente , Alta do Paciente , Desnutrição Proteico-Calórica/sangue , Desnutrição Proteico-Calórica/classificação , Desnutrição Proteico-Calórica/mortalidade , Índice de Gravidade de Doença , Estresse Fisiológico/induzido quimicamente , Taxa de SobrevidaRESUMO
Entre las enfermedades mas frecuentes que afecta a nuestra población está la desnutrición en sus diversos grados. Y la que causa la mortalidad elevada, dejando secuelas invalidantes, es precisamente la desnutrición grave. La producción adecuada de hormona tiroidea es fundamental para el mantenimiento de la función normal de casi todas las células del organismo, desde el final del primer trimestre de vida fetal hasta la muerte. Aunque todabía no se conoce completamente su mecanismo de acción, la hormona tiroidea es esencial para el crecimiento, el desarrollo y las funciones normales. Tanto un exceso como un deficit pueden tener consecuencias graves, y en ocaciones irreversibles. Como consecuencia de la restricción de nutrientes, el organismo del niño indispensablemente debe realizar una serie de mecanismos adaptivos que le permitan mantener su vida, donde necesariamente deben ser regidos por el sistema endócrino. Por lo tanto cada niño que sufre desnutrición extrema, se convierte en un problema dificil, y los resultados de experiencias foraneas son contradictorias, que facilmente nos llevan a la confusión. Además de que existen otros factores que pudiesen influir como: ambiente familiar etc.