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Acetylator status of kwashiorkor children in Ibadan (south-west Nigeria).

Acetylator status was determined in 25 kwashiorkor children, aged between 8 months and 3 years and in 25 age-matched control group of healthy children after a single oral dose of sulphamethazine (40 mg/kg body weight) and by measuring the acetylated sulphamethazine in blood samples, collected 6 h after the administration of sulphamethazine. The percentage of slow acetylators among kwashiorkor children was 40% while among the control group of children it was 48%. The difference between the two groups was not significant. Therefore, it is probable that the slow acetylator status of the Nigerian African children may not be a contributing factor for the development of kwashiorkor, a syndrome of protein-energy malnutrition. Furthermore, the polymorphic activity of N-acetyl transferase enzyme may not be impaired in kwashiorkor.

Acetylation↗

Intensive nursing care of kwashiorkor in Malawi.

The case fatality rate for children with kwashiorkor in central hospitals in Malawi was 30.5% (275/901) in 1995. The purpose of this study was to determine whether improved case management with intensive nursing care could lower this case fatality rate. A total of 75 children admitted with kwashiorkor in Blantyre, Malawi, received intensive nursing care. This included nursing in individual clean beds with blankets, a nurse:child ratio of 1:3, supervised feedings every 2 h, a paediatrician with expertise in treating kwashiorkor always available for consultation, laboratory evaluation for systemic infection and empiric use of ceftriaxone. Nineteen of these children died (25%). The causes of death were life threatening electrolyte abnormalities (hypokalaemia, hyponatraemia, hypophosphataemia) in nine cases, overwhelming infection in eight cases and congestive heart failure in two children. Children infected with the human immunodeficiency virus were more likely to die (9/20), as were children with life threatening electrolyte abnormalities (9/15) and children with more severe wasting. When compared with 225 children treated in the same year at the same institution, who were carefully matched for severity of kwashiorkor, intensive nursing did not improve overall survival.

Cause of Death↗

Serotonin metabolism in children with kwashiorkor.

Intestinal fat absorption, serum 5-hydroxytryptamine (5-HT) and 24-hour urinary excretion of 5-hydroxyindoleacetic acid (5-HIAA) were studied in 13 children with kwashiorkor and 10 matched healthy controls. Eight out of 13 children with kwashiorkor who had steatorrhea also showed raised plasma serotonin levels in parallel with the high urinary excretion of 5-HIAA. In five children with kwashiorkor who showed normal intestinal fat absorption, the serum 5-HT and urinary 5-HIAA levels were comparable to controls. After therapy, concurrent with clinical and biochemical recovery, the intestinal absorption of fat improved, serum 5-HT concentration and the urinary excretion of 5-HIAA returned to normal range. This suggested that the deranged serotonin metabolism in our cases was secondary to the protein-calorie deficiency. The presence of defective metabolism of serotonin (5-HT) in children with kwashiorkor has been reported and its possible role in the etiopathogenesis of steatorrhea-diarrhea, skin lesions and psychomotor changes has been suggested for further work.

Blood Proteins↗

Effect of severe kwashiorkor on intellectual development among Nigerian children.

A study was conducted to investigated the intellectual sequelae of severe kwashiorkor among Nigerian children of school age. The design for the study had an experimental urban kwashiorkor (index) group and four control groups, namely, a sibling group, a lower class group, an upper class group, and a rural kwashiorkor group. Various psychological tests measuring specific intellectual abilities were administered to all of the subjects taking part in the study. The findings showed that the index group had lower levels of certain types of intellectual skill-specifically the higher cognitive skills-at school age than their siblings, and more so than other controls except their rural counterparts; males showed a tendency to be more affected by severe kwashiorkor with regard to mental development than their female counterparts; there was no relationship between scores in the psychological tests and the ages at which the index cases were admitted into hospital; the upper class was clearly superior in performance of the tests and also in measures of weight and head measurements when compared to all of the other groups; there was no relationship between head circumference and scores in the tests among subjects in the five groups.

Anthropometry↗

Kwashiorkor in North America.

The controversy regarding the relative importance of protein vs energy deficiency in the genesis of kwashiorkor has not been resolved by studies of protein-energy malnutrition (PEM) in developing countries. Cases of edematous PEM (n = 29) in North America on the other hand provide clear indications that protein deficiency is an essential prerequisite for the development of kwashiorkor and marasmic kwashiorkor. Energy intakes may vary from low to high and the main source of energy may be carbohydrate or fat. These findings are in keeping with experimental evidence that a low ratio of protein to energy disrupts the usual hypometabolic response to dietary deficiency and leads to hypoalbuminemia and consequent edema. Protein supplements should be a part of programs aimed at preventing kwashiorkor.

Anthropometry↗

Whole-body protein kinetics in children with kwashiorkor and infection: a comparison of egg white and milk as dietary sources of protein.

This study tested the hypothesis that during treatment of kwashiorkor (including marasmic kwashiorkor) with infection there is a lower rate of amino acid oxidation when the dietary intake of amino acids resembles the amino acid composition of acute phase proteins (APPs). Twenty-two children in Blantyre, Malawi, with kwashiorkor and acute infection were fed an isoenergetic, isonitrogenous diet with either egg white or milk as a protein source. The whole-body amino acid oxidation rate was measured after 24 h by determining the plasma urea rate of appearance, and whole-body protein breakdown and synthesis rates were determined from the plasma leucine rate of appearance. Plasma concentrations of C-reactive protein, alpha1-antitrypsin, tumor necrosis factor alpha (TNF-alpha), and interleukin 6 (IL-6) were determined on admission and at 24 and 48 h. The 11 children who received milk had a lower rate of amino acid oxidation than the children who received egg white (x +/- SD: 137 +/- 65 compared with 195 +/- 66 micromol urea x kg body wt(-1) x h(-1), P < 0.05). No significant differences were found between the two groups in the rate of whole-body protein breakdown or protein synthesis. The TNF-alpha concentration correlated inversely with whole-body protein breakdown and synthesis rates, and the IL-6 concentration correlated directly with C-reactive protein. We conclude that by making the amino acid composition of the diet resemble that of APPs in the treatment of acute kwashiorkor, the rate of amino acid oxidation can be decreased.

C-Reactive Protein↗

Leucocyte function in children with kwashiorkor.

A study of leucocyte response to infection, polymorphonuclear leucocyte chemotaxis and bactericidal activity, and nitroblue tetrazolium (NBT) reduction in children with kwashiorkor was undertaken and compared with a control group. The results show that total leucocyte counts were depressed in children with kwashiorkor, and lymphopenia was not infrequent. NBT reduction was normal. Abnormal polymorphonuclear leucocyte chemotaxis and bactericidal activity, though frequently found in children with kwashiorkor, was shown to be dependent on infection and not on protein depletion per se. Therefore, apart from some impairment of leucocyte mobilization in the presence of infection, the qualtiy of polymorphonuclear function, as determined by the above techniques, appears to be normal in kwashiorkor.

Blood Bactericidal Activity↗

Plasma free iron: a possible cause of oedema in kwashiorkor.

BACKGROUND: Oedema is a sine qua non for the diagnosis of kwashiorkor yet the mechanisms leading to oedema remain ill defined. AIMS: To relate the plasma concentration of radical promoting 'free' iron to the degree of oedema in patients with kwashiorkor. SETTING: University teaching hospital. PATIENTS: Fifteen children with kwashiorkor, nine of whom had severe and six of whom had a moderate degree of oedema. METHODS: Plasma 'free' iron was measured as bleomycin detectable iron (BDI) and related to severity of oedema and plasma albumin concentration. RESULTS: BDI was significantly higher in the patients with severe oedema (20.5 v 6.75 mumol/l) whereas the albumin concentrations were similar (16 v 17 g/l). BDI was no longer present in any patients 30 days after admission. CONCLUSIONS: 'Free' circulating iron may contribute to the oedema of kwashiorkor, and its sequestration could hasten recovery and decrease morbidity and mortality.

Child↗

Antioxidant status and nitric oxide in the malnutrition syndrome kwashiorkor.

The pathophysiology of kwashiorkor, a severe edematous manifestation of malnutrition, is still poorly understood. The syndrome is, however, known to be associated with alterations in redox metabolism. To further elucidate the role of oxidative stress in kwashiorkor, we carried out a longitudinal study on the major blood antioxidants at the St. Joseph's Hospital, Jirapa, Ghana. All kwashiorkor patients (K) were followed up for 20 d. In comparison with local healthy controls (C), the plasma total antioxidant status was reduced to less than 50% in the patients (C, 0.87 +/- 0.21 mM; K, 0.40 +/- 0.20 mM; p<0.001). Similarly, the major plasma antioxidant albumin (C, 40.9 +/- 2.5 g/L; K, 19.1 +/- 7.4 g/L; p < 0.001) and erythrocyte glutathione (C, 2.39 +/- 0.28 mM; K, 1.01 +/- 0.33; p < 0.001) were decreased, whereas the levels of bilirubin and uric acid were not significantly altered. Nitrite and nitrate were found to be increased by a factor of 2 in kwashiorkor (C, 120 +/- 46 microM; K, 235 +/- 107 microM; p < 0.001). Over the observation period, the trends of albumin and glutathione levels were related to clinical outcome. These concentrations rose in patients who recovered and fell in patients who did not. Our study strongly supports the hypothesis that oxidative and nitrosative stress play a role in the pathophysiology of edematous malnutrition. Prophylactic and therapeutic strategies should aim at the careful correction of the reduced antioxidant status of the patients.

Adolescent↗

Misplaced iron in kwashiorkor.

OBJECTIVES: To determine the presence of radical promoting iron (non-protein-bound or loosely bound or free iron) in the plasma of children with kwashiorkor. DESIGN: The bleomycin assay was employed for the quantitation of free or loosely bound iron. SETTING: The Red Cross War Memorial Children's Hospital, Cape Town, Tertiary Care. SUBJECTS: Fifty children on admission with kwashiorkor: six with marasmus and twelve healthy well-nourished controls. RESULTS: Non-protein-bound iron was detected in the plasma of 58% of children with kwashiorkor but was absent in marasmic and healthy well-nourished children. CONCLUSIONS: The presence of radical promoting iron supports the hypothesis that a free radical injury probably plays a role in the pathogenesis of kwashiorkor and its removal may improve mortality.

Bleomycin↗

Cortisol and growth hormone in kwashiorkor and marasmus.

Cortisol and growth hormone concentrations in the plasma were determined in 26 children with kwashiorkor, 13 with marasmus, and 21 controls. Cortisol levels were high in babies with kwashiorkor and marasmus, but higher in the former, in relation to a constant body mass. The concentration of plasma cortisol correlated positively with the body mass deficit in kwashiorkor (r = 0,66) and in children with low mass for age (r = 0,75). Growth hormone levels were elevated in both kwashiorkor and marasmus. The proposed role of these hormones in metabolic adaptation to malnutrition is discussed.

Body Weight↗

Plasma concentration of taurine is higher in malnourished than control children: differences between kwashiorkor and marasmus.

Plasma free amino acids were determined in the plasma of severely malnourished children under two years of age. A total of thirty-one patients and eleven controls were evaluated: seventeen cases of kwashiorkor, eight cases of marasmus, and six cases of marasmic-kwashiorkor. Fasting plasma samples were taken in the morning on the day of admission. Fasting plasma samples were also taken from nine patients at discharge after two months in the hospital where they received a balanced diet as treatment. A partial reversal of the signs of malnutrition was observed at discharge. In the whole group of patients ad admission, lower concentrations of tyrosine, methionine, tryptophan, and leucine and higher concentrations of aspartate, glutamate, and taurine were observed compared to controls. Taurine continued to be elevated in the malnourished group at the time of discharge. Marasmic children, as compared to controls, had high aspartate and low tryptophan levels, but taurine levels were not significantly different from controls. Kwashiorkor patients had low tyrosine, methionine, tryptophan, and lysine, and significantly higher taurine plasma levels. The elevated concentration of taurine might be the result of a redistribution of this amino acid to provide specific tissues with the required amount for development.

Amino Acids↗

Nitrosamine metabolism in kwashiorkor rats.

The in vitro metabolism of nitrosodimethylamine (NDMA) was studied in liver tissue obtained from male weanling kwashiorkor wistar rats. The elimination of this compound and that of nitrosomorpholine (NMOR) from the blood, after a single intravenous dose, was also investigated. N-demethylase activity in liver microsomes of the test animals was not significantly different from that of the controls although the activity of this enzyme per gram wet liver tissue was considerably reduced in the model animals. On the other hand, the glutathione (GSH) content in liver cytosol of the kwashiorkor animals was much higher than that of the controls. The elimination of NDMA and NMOR from the blood of the experimental animals over 8 hr following i.v. administration of the carcinogens, showed that the clearance rate of each nitrosamine was significantly lower in the kwashiorkor rats.

Animals↗

Kwashiorkor.

Kwashiorkor kills millions of young children in the tropical Third World. It was believed to be a disease of protein starvation. The medical team headed by Professor Ralph Henrickse of the Liverpool School of Tropical Medicine has discovered that aflatoxin, a fungus toxin, may be the triggering factor in this disease which also impairs liver function. In New Zealand, we have a pasture fungus, the spores of which produce a liver toxin that has killed millions of animals this century and impaired the performance of millions more. New Zealand is a pastoral farming country with 70 million sheep and several million cattle. We now protect the animal with zinc medication. This paper describes the similarities between Kwashiorkor and the mycotoxic liver disease in New Zealand livestock, known locally as Facial Eczema. It describes briefly my discovery that pharmacological doses of zinc protected farm animals from pasture contaminated with the spores of the fungus Pithomyces chartarum, which contains the toxin sporidesmin. This paper proposes that Kwashiorkor and Facial Eczema are diseases with similar beginnings and a common end.

Aflatoxins↗

A case of kwashiorkor in the UK.

A case of kwashiorkor in a British child of Caucasian origin is described. The 5-year-old boy was referred to hospital for investigation of a persistent anaemia, but on examination was found to have classical features of kwashiorkor. He was stunted with both height and weight below the fifth centile and had mild pitting oedema in both legs. His hair was pale and easily pluckable and a soft liver edge was palpable. Plasma albumin concentration was 16 g/l and the plasma amino acid pattern, which revealed markedly reduced levels of essential but normal to high non-essential amino acids, was similar to that described in kwashiorkor in Uganda. A dietary history revealed that for about 2 years the child's diet had contained very little protein but adequate energy and had been supplemented with multivitamin pills. There was no evidence of other pathology, neglect or abuse and the child responded rapidly to refeeding with a balanced diet.

Amino Acids↗

Serum colloidal osmotic pressure in the development of kwashiorkor and in recovery: its relationship to albumin and globulin concentrations and oedema.

1. Serum colloidal osmotic pressure was measured in children 'at risk' to kwashiorkor, in other with frank signs of the disease and during recovery. Simultaneous estimations of serum albumin and globulin concentrations and assessments of the extent of oedema were also made. 2. During the development of kwashiorkor, serum colloidal osmotic pressure did not decrease significantly until albumin concentration was 25-1--27-5 g/l. Above 30-0 g/1, colloidal osmotic pressure was maintained at normal levels during which time a significant reciprocal relationship existed between albumin and globulin concentrations. These findings provide support for suggestions that there may be on oncotic regulation of albumin synthesis. 3. Low albumin concentrations were mainly responsible for the low colloidal osmotic pressures found in children with kwashiorkor and in agreement and previous findings the threshold for the formation of oncotic oedema was found to be about 2-35--2-65 kN/m2. 4. Values for colloidal osmotic pressure calculated from serum albumin and gobulin concentrations using emprical formulas did not agree well with measured values and no constant correction factor suitable over the whole range of albumin concentrations found in rural Ugandan children could be devised. In many hypoalbuminaemic children ony direct measurement of serum colloidal pressure will indicate the true extent of risk to an episode of oedema.

Child↗

Increased oxidative stress in kwashiorkor.

To test the hypothesis that kwashiorkor is associated with increased oxidative stress, urinary concentrations of 2 oxidized amino acids, o,o '-dityrosine and ortho -tyrosine, were measured by gas chromatography-mass spectrometry. Children with kwashiorkor, with or without infection, had a 3- to 7-fold increase in urinary o,o '-dityrosine and a 1.5- to 2-fold increase in ortho -tyrosine when compared with well-nourished children. This observation raises the possibility that oxidative damage to proteins and other biologic targets plays a role in the clinical manifestations of kwashiorkor.

Child, Preschool↗

Selective deficiency of hepatic triglyceride lipase and hypertriglyceridaemia in kwashiorkor.

1. Serum postheparin lipolytic activities (PHLA), triglyceride and free fatty acid concentrations were determined in children with kwashiorkor before and after treatment and also in normal control children. 2. Using the range (571-1650 mumol/l) of serum triglyceride of the control children as normal, five (20%) of the twenty-five children with kwashiorkor had low (less than 570 mumol/l), thirteen (52%) had normal (571-1650 mumol/l) and seven (28%) had high (more than 1650 mumol/l) serum triglyceride levels. 3. The serum PHLA did not show any definite correlation with the level of circulating triglycerides, although the lowest levels of PHLA were found in the malnourished children with highest triglyceride level. 4. While the hepatic PHLA in the malnourished children was significantly less than control value, the extrahepatic PHLA did not differ significantly. 5. After treatment, serum PHLA rose significantly and the mean levels were within normal range. 6. Our findings suggest that a defect in catabolism of very-low-density lipoprotein caused by a low hepatic PHLA may cause hypertriglyceridaemia in children with kwashiorkor.

Body Weight↗