RESUMO
Brain function in 10 severely malnourished children and matched controls was assessed using spectral analysis of electroencephalographic responses to photic driving during slow-wave sleep. The percentage power in the classical EEG broad-band domains was derived from temporo-occipital records. The malnourished group (5-23 months old; z-score height-for-age -3.2 +/- 0.3, weight-for-height -2.5 +/- 0.3) were tested on admission and on discharge from hospital. No significant differences were found between admission and discharge. Significant differences were found between malnourished and control groups, in the alpha 1 band in the undriven EEG, and in the alpha/beta 1 power ratio while driving at 8 Hz. These electrophysiological abnormalities, persisting despite somatic rehabilitation, must be associated with the chronic rather than the acute aspects of malnutrition, and can index the deviation of brain function from normality.
Assuntos
Encéfalo/fisiologia , Eletroencefalografia , Distúrbios Nutricionais/diagnóstico , Estatura , Peso Corporal , Feminino , Humanos , Lactente , Masculino , Índice de Gravidade de DoençaRESUMO
The enzyme glyoxalase I (Glyox I) is involved in metabolic detoxification, and requires glutathione (GSH) as a cofactor. Given the low concentration of whole blood GSH in children with oedematous malnutrition, it is possible that the function of this pathway may be compromised in these children. Glyox I activity was therefore assayed in erythrocytes taken from 133 severely malnourished children and 21 age-matched controls. The mean values (+/- SEM) for the marasmic group (Marasmus: 105 +/- 4/u/gm Hb) and the group with kwashiorkor (Kwash: 103 +/- 4/u/gm Hb) were not significantly different from controls (Cont: 104 +/- 2 u/gm Hb). In the group with marasmic-kwashiorkor (M-K: 88 +/- 4 u/g Hb) Glyox I activity was significantly lower than in controls (p < 0.005), as well as in children with Marasmus (p < 0.005), and kwashiorkor (p < 0.05). Enzyme activity was lower than normal in 45% of the MK group. Seven children died subsequent to admission; in five cases Glyox I activities were exceedingly low. There was a weak positive correlation between Glyox I activity and whole blood levels of GSH (r = 0.215). We conclude that Glyox I activity is relatively unaffected in malnutrition, except in those with M-K and especially those who do not survive the acutely malnourished state.
Assuntos
Países em Desenvolvimento , Lactoilglutationa Liase/sangue , Desnutrição Proteico-Calórica/enzimologia , Criança , Pré-Escolar , Eritrócitos/enzimologia , Feminino , Deficiência de Glucosefosfato Desidrogenase/enzimologia , Deficiência de Glucosefosfato Desidrogenase/genética , Glutationa/sangue , Humanos , Lactente , Jamaica , Masculino , Desnutrição Proteico-Calórica/diagnóstico , Valores de ReferênciaRESUMO
The autopsy records of 115 children with severe protein-energy malnutrition were reviewed. Sections of the lung histology showed evidence of bacterial pneumonia in 49% of cases. An additional 18% showed bronchitis, bronchiolitis or interstitial pneumonitis. Aspiration of gastric contents was evident in 10% of cases; 6% showed pulmonary oedema and congestion. In the remaining cases, no lung pathology was identified (17%). In 8 cases, rapid autopsy examination permitted fixation of lung tissue for electron microscopy. These included 4 cases of bronchopneumonia, one of which was associated with viral pneumonia. Another interstitial pneumonitis, probably of viral aetiology, was also studied. Both these virus-associated cases showed loss of type I pneumocytes and hyperplasia of type II pneumocytes. Another patient with herpes simplex hepatitis showed necrotic emboli in pulmonary capillaries with virions, as well as colonies of interstitial bacteria. One patient with acute pulmonary oedema displayed severe endothelial cell swelling on electron microscopy. In one case, there was no evidence of respiratory changes, apart from desquamation of type I pneumocytes. Useful information can be obtained on the fine structure of the lung, using samples taken soon after death.
Assuntos
Pulmão/patologia , Desnutrição Proteico-Calórica/patologia , Feminino , Humanos , Lactente , Jamaica , Pulmão/ultraestrutura , MasculinoRESUMO
Liver specimens obtained immediately after death from eight severely malnourished children were examined by electron microscopy, and compared with seven liver biopsy specimens from children who had recovered from malnutrition. The liver cells from the fatal cases showed mitochondrial swelling, with coarse densities in the matrix, cholestasis, depletion of the endoplasmic reticulum and Golgi apparatus, diminished glycogen stores, prominent lipid deposits and focal cytoplasmic degradation. The nucleoli were enlarged. There was marked reduction in peroxisomes. In contrast, the biopsies from recovering children showed good cellular organisation, and a normal frequency of peroxisomes. Multiple factors, including sepsis, may lead to depletion of peroxisomes. Loss of peroxisomes may interrupt beta-oxidation of long-chain fatty acids and accentuate the accumulation of lipid. Moreover, a reduction in the concentration of catalase may remove one avenue for the detoxification of free radicals. As the concentration of other anti-oxidants, notably glutathione, is also reduced, free radical damage may occur, leading to lipid peroxidation of membranes, mitochondrial damage, pump failure and influx of water and electrolytes into the cell.
Assuntos
Países em Desenvolvimento , Fígado/patologia , Microcorpos/ultraestrutura , Desnutrição Proteico-Calórica/patologia , Biópsia , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Jamaica , Masculino , Microscopia Eletrônica , Mitocôndrias Hepáticas/ultraestrutura , Dilatação Mitocondrial/fisiologiaRESUMO
1. Cytokine production in vitro was assessed in 16 malnourished children, before and after nutritional recovery. 2. Tumour necrosis factor-alpha and interleukin-6 were measured in whole blood after lipopolysaccharide stimulation. 3. The total amount of both cytokines was significantly less after 24 h incubation among malnourished children when compared with the same children after nutritional rehabilitation. 4. Cytokine production in vitro is impaired in severely malnourished children.
Assuntos
Interleucina-6/biossíntese , Leucócitos/metabolismo , Distúrbios Nutricionais/sangue , Fator de Necrose Tumoral alfa/biossíntese , Feminino , Humanos , Técnicas In Vitro , Lactente , Leucócitos/efeitos dos fármacos , Lipopolissacarídeos/farmacologia , MasculinoRESUMO
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
Significant hormonal changes have been reported in childhood malnutrition, including high serum levels of growth hormone and cortisol, and low levels of circulating insulin. The ultrastructure of the endocrine pancreas in such patients has hitherto not been reported. A light microscopy survey of the pancreatic islets was carried out on 69 malnourished children dying from protein-energy malnutrition. In seven of these cases, a rapid autopsy protocol allowed tissues to be fixed for electron microscopy within 75 minutes of death. This paper presents the first ultrastructural observations on the Islets of Langerhans in childhood protein-energy malnutrition. In all cases, there was a variable degree of degeneration of all cell types with membrane damage, loss of ribosomes, vesiculation and mitochondrial swelling. In addition, the B-cells showed a high proportion of precursor granules compared to crystal forms, possibly accounting for low insulin serum levels reported by other workers. It is suggested that islet cell changes may be related to free radical damage secondary to depletion of glutathione and other antioxidants, as well as relative deficiencies of cysteine and zinc. In addition, the effects of agonal anoxia, and a short fixation delay after death must be considered.
Assuntos
Ilhotas Pancreáticas/ultraestrutura , Desnutrição Proteico-Calórica/patologia , Feminino , Hormônio do Crescimento/sangue , Humanos , Hidrocortisona/sangue , Lactente , Jamaica , Masculino , Microscopia Eletrônica , Organelas/ultraestruturaRESUMO
1. The responses of plasma levels of C-reactive protein and serum amyloid A were assessed in two groups of malnourished children. 2. Sixty-six severely malnourished children were studied at admission. Fifty of these had clinical and/or laboratory evidence of infection. C-reactive protein was not elevated in 23 (46%) and serum amyloid A was not raised in 29 (58%) of these 50 children. 3. Surviving children (n = 62) received two doses of diphtheria-pertussis-tetanus vaccine, to which the C-reactive protein and serum amyloid A responses were measured. The first was given early in recovery, the second after nutritional rehabilitation. Ten mildly malnourished children acted as controls, receiving a single dose of diphtheria-pertussis-tetanus vaccine. 4. The responses of both C-reactive protein and serum amyloid A to diphtheria-pertussis-tetanus vaccine were significantly less in early recovery than after nutritional recovery. The response of the mildly malnourished group was no different from that of the severely malnourished group in early recovery, but was less than their response on discharge. 5. The acute-phase protein response of malnourished children is impaired. This may have prognostic implications as the response plays a central role in promoting healing.
Assuntos
Proteína C-Reativa/biossíntese , Distúrbios Nutricionais/sangue , Proteína Amiloide A Sérica/biossíntese , Doença Aguda , Infecções Bacterianas/metabolismo , Pré-Escolar , Vacina contra Difteria, Tétano e Coqueluche/administração & dosagem , Feminino , Humanos , Lactente , MasculinoRESUMO
Immunosuppression increases the susceptibility to infection and changes the inflammatory response in children with severe protein-energy malnutrition. In this 5-year prospective study bacteremia was documented in 16% of 336 severely malnourished children, 2 to 34 months of age, who were hospitalized consecutively in the Tropical Metabolism Research Unit, Kingston, Jamaica. The 53 children had 60 episodes of nosocomial and community-acquired bacteremia with 69 blood isolates. Community-acquired bacteremia accounted for 72% (43 of 60) of bacteremic episodes. Thirty-five percent (24 of 69) of the strains were coagulase-negative staphylococci, 19% (13 of 69) were Staphylococcus aureus and 11% (8 of 69) were Streptococcus Group D. Seventeen episodes of coagulase-negative staphylococcal bacteremia were acquired in the community and 7 were nosocomial. These patients were more likely to have pneumonic consolidation than children with all other bacteremias combined (P < 0.02, Fisher's exact test). The bacteremia-related case fatality rate was 8% (5 of 60). Polymicrobial and Gram-negative septicemia were independent positive predictive factors for mortality when compared with single-agent and Gram-positive sepsis (P < 0.02). This 71% (49 of 69) prevalence of Gram-positive organisms suggests a change in the epidemiology from the predominant Gram-negative etiologies (76%) described in previous reports.
Assuntos
Bacteriemia/complicações , Bacteriemia/microbiologia , Desnutrição Proteico-Calórica/complicações , Infecções Estafilocócicas/complicações , Bacteriemia/epidemiologia , Pré-Escolar , Coagulase , Feminino , Humanos , Lactente , Jamaica/epidemiologia , Masculino , Estudos Prospectivos , Desnutrição Proteico-Calórica/epidemiologiaRESUMO
Ultrasonographic, blinded assessment was made of the extent of hepatic steatosis in 55 children with severe malnutrition: undernutrition (n = 6), marasmus (n = 18), marasmickwashiorkor (n = 17), and kwashiorkor (n = 14). The children were examined on admission, in early recovery (considered as baseline), and again at discharge. Eleven healthy control children and eight of the previously malnourished children were studied as comparison groups. Both oedematous and non-oedematous malnourished children had significantly more steatosis than the comparison groups at each time. Children with oedematous malnutrition had significantly greater steatosis than non-oedematous children at admission. Half of the non-oedematous malnourished children had appreciable hepatic steatosis at both admission and at baseline. Hepatic fat was only slowly mobilised. The rate constant was 1.4 +/- 0.3%/day. One quarter of the children did not change steatosis grades during the period they were in hospital. There was no overall correlation between the extent of steatosis and liver size. Hepatic steatosis in childhood malnutrition is not confined to oedematous children: it is frequently present in marasmic and undernourished children. Its extent is not necessarily related to the degree of hepatomegaly and accumulated lipid is only slowly mobilised.