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.

Bone marrow and chelatable iron in patients with protein energy malnutrition.

OBJECTIVES: To examine the iron status of malnourished children by comparing bone marrow iron deposits in children with protein energy malnutrition with those in well-nourished controls, and measuring chelatable urinary iron excretion in children with kwashiorkor. DESIGN: Bone marrow iron was assessed histologically in postmortem specimens from children with kwashiorkor or marasmus, and from controls. Twenty-four-hour urinary iron was measured in children with severe kwashiorkor, half of whom received 10 mg/kg of intramuscular desferrioxamine (DFO) on admission. SETTING: Red Cross War Memorial Children's Hospital, Cape Town. SUBJECTS: Thirteen children with kwashiorkor, 6 with marasmus and 16 well-nourished children underwent bone marrow examination. Urinary iron excretion was assayed in 17 children with kwashiorkor. RESULTS: Stainable iron was present in the bone marrow of half the children with kwashiorkor but in only 1 child in each of the other groups. The median iron excretion was 945.5 micrograms/24 hours in the DFO group compared with 28.5 micrograms/24 hours in the non-DFO group. CONCLUSIONS: There is an apparent excess of iron which may predispose to bacterial infections and free radical-mediated injury in children with kwashiorkor.

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.

Recombinant human erythropoietin in the treatment of the anemia of prematurity: results of a double-blind, placebo-controlled study.

OBJECTIVE: To assess the efficacy of recombinant human erythropoietin (rHuEpo) in the treatment of the anemia of prematurity. METHODOLOGY: A double-blind, placebo-controlled study was conducted on 80 preterm infants (< or = 32 weeks; postnatal age, 2 to 8 weeks; central hematocrit < or = 35%). Patients were randomly assigned to receive subcutaneous rHuEpo (Eprex, 600 U/kg per week) or an equivalent volume of placebo, for up to 6 weeks. All patients received supplements of vitamin E (25 IU) and iron (3 mg/kg per day). The iron supplement was increased if declining serum ferritin measurements were noted. RESULTS: Treatment and placebo groups did not differ significantly with respect to mean gestational age, birth weight, hematocrit, or reticulocyte count at study entry. Fewer transfusions were administered to those receiving erythropoietin (7 compared with 21; P = .002). Compared with the placebo group, the infants receiving rHuEpo had a higher mean hematocrit (32.3 +/- 4% vs 29.3 +/- 6.2%; P = .014) and absolute reticulocyte count (223 +/- 73 vs 124.9 +/- 73 x 10(9)/L; P < .001) at the end of the study. The mean neutrophil count was not significantly reduced at study exit (P = .8), nor at any other period during the trial in the rHuEpo group. Intercurrent events (mostly infections) were not increased in the treatment group, although there was one case of sudden infant death syndrome at age 4 months. CONCLUSIONS: Using a dose of rHuEpo of 600 U/kg per week, this study has shown a clear reduction in the requirement for blood transfusion in preterm infants.

The social, family and medical backgrounds of children with kwashiorkor presenting at a teaching hospital.

The social, family and medical backgrounds of 53 children hospitalised with kwashiorkor were compared with those of 106 children hospitalised for non-nutritional diseases to determine risk factors for severe nutritional disease in children presenting to a teaching hospital. The control children were matched for age, sex, race and the non-nutritional illness complicating the course of the children with kwashiorkor; in 80% of cases the reason for admission was either gastro-enteritis or pneumonia. A major difference between the groups was the educational status of the mothers. Only 57% of the mothers of the children with kwashiorkor were literate compared with 93% of the controls; 25% as opposed to 47% were married, and 36% as opposed to 72% received support from the father. There were no differences in the mothers' ages or use of contraception, or in the number of children they had. In all except 1 instance the child with kwashiorkor was the youngest or only child in the family, and the average sibling interval was 53 months. The types of dwellings occupied by the families were similar, but overcrowding was worse in the kwashiorkor group. Family income was below the household subsistence level in the vast majority of both groups, but significantly more of the kwashiorkor group had minimal cash income. Significantly fewer of the children with kwashiorkor had been breast-fed or adequately immunised, and 60% had previously been hospitalised for dehydrating diarrhoea. This study demonstrates that in an urban environment the traditional factors of large families and displacement by a younger sibling are not associated with kwashiorkor.(ABSTRACT TRUNCATED AT 250 WORDS)

Red blood cell antioxidant enzyme concentrations in kwashiorkor and marasmus.

Kwashiorkor may occur when an imbalance between pro- and antioxidants in malnourished children results in an excess of free radicals. The concentrations of the antioxidant enzymes catalase (CAT), superoxide dismutase (SOD), reduced glutathione (GSH) and glutathione peroxidase (GPX) were measured in erythrocytes of 22 children with kwashiorkor on admission to hospital and repeated on days 5, 10 and 30 of recovery. The concentrations were compared with those in 22 children with marasmus and in 20 children who were normally nourished but had infective illness necessitating their hospitalization. CAT and SOD were similar in all groups and did not change during recovery. GSH and GPX were significantly lower in kwashiorkor than in the other groups. Concentrations of thiobarbituric acid-reactive substances (TBARS), a marker of lipid peroxidation, were significantly elevated in children with kwashiorkor. During clinical recovery, GSH but not GPX concentrations rose despite an increase in plasma selenium levels and decreased concentrations of TBARS. These findings suggest that the antioxidant status of children with kwashiorkor differs from that of well nourished and marasmic children. Whether these differences are the cause of the consequence of the clinical picture is unresolved.

Reversible cerebral shrinkage in kwashiorkor: an MRI study.

Protein energy malnutrition is associated with cerebral atrophy which may be detrimental to intellectual development. The aim of this study was to document the anatomical abnormalities which lead to the appearance of cerebral atrophy using magnetic resonance imaging (MRI) in the acute stage of kwashiorkor and to monitor changes during nutritional rehabilitation. Twelve children aged 6 to 37 months requiring admission to hospital for the treatment of kwashiorkor were studied. The children were evaluated clinically, biochemically, and by MRI of their brains on admission and 30 and 90 days later. Brain shrinkage was present in every child on admission. White and grey matter appeared equally affected and the myelination was normal for age. At 90 days, the cerebral changes had resolved in nine and improved substantially in the remainder, by which time serum proteins and weight for age were within the normal range. The findings of this study suggest that brain shrinkage associated with kwashiorkor reverses rapidly with nutritional rehabilitation.

Plasma zinc, copper, selenium, ferritin and whole blood manganese concentrations in children with kwashiorkor in the acute stage and during refeeding.

Plasma zinc, copper, selenium, ferritin and whole blood manganese concentrations were measured in 22 children with kwashiorkor on admission to hospital and on days 5, 10 and 30 of refeeding. Twenty similarly aged, healthy, well nourished children served as controls. The mean (SEM) zinc, copper and selenium concentrations of 7.5 (0.93), 10.8 (0.64) and 0.29 (0.02) mumol/l, respectively, in the children with kwashiorkor on admission were all significantly lower than the values of 13.7 (0.66), 25.6 (1.72) and 0.72 (0.04) mumol/l in the controls. In contrast, the erythrocyte manganese level of 1.67 (0.09) micrograms/gHb and the median ferritin concentration of 293 micrograms/dl were significantly higher than in the controls. After 30 days there was full clinical recovery with significant weight gain and a return of the plasma albumin, caeruloplasmin, copper and ferritin to normal. However, manganese remained elevated and zinc and selenium concentrations remained significantly low. Our results suggest that nutritional rehabilitation of children with kwashiorkor is incomplete by 30 days and cannot be judged purely by a return of the plasma proteins to normal. Addition of selected trace elements to the diet may hasten full recovery.

Post-exercise ketosis in post-prandial exercise: effect of glucose and alanine ingestion in humans.

This study examined ketosis in response to 90 min of running before and after the ingestion of 50 g glucose or 50 g L-alanine in thirty-three athletes. Everyone ran 20 km at 07.30 h and then rested, while fasting, till 16.00 h. There were four test groups: 'glucose-before', 'glucose-after', 'alanine-before' and 'alanine-after' according to whether glucose or alanine was ingested at 07.00 h, or 09.00 h. Controls did not ingest either test substance. The control 3-hydroxybutyrate concentration rose from 0.23 +/- 0.03 mmol/l (S.E. of mean) at 07.00 h to 0.74 +/- 0.27 mmol/l at 12.00 h, and 0.94 +/- 0.33 mmol/l at 16.00 h. Glucose ingestion before or after exercise did not influence post-exercise ketosis significantly, despite high insulin: glucagon ratios, low free fatty acid concentrations and hyperglycaemia. Alanine significantly lowered the 3-hydroxybutyrate levels, especially after exercise (to 0.14 +/- 0.07 mmol/l at 12.00 h; P less than 0.05) despite reversed insulin: glucagon ratios. This suggests that hepatic responsiveness to portal hyperglycaemia and the main hormones of metabolism is altered immediately after exercise, presumably to promote muscle glycogen synthesis in preference to liver glycogen synthesis.

Adrenergic modulation of human pancreatic polypeptide (hPP) release.

Serum human pancreatic polypeptide (hPP) responses to adrenergic modulation were measured in 24 normal subjects. Epinephrine (6 microgram/min) was infused to stimulate adrenergic alpha- and beta-receptors. Beta-receptor stimulation was achieved by infusing epinephrine and selectively blocking alpha- receptors with phentolamine, and alpha-receptor stimulation was achieved by infusing epinephrine and blocking beta-receptors with propranolol. Combined alpha- and beta-receptor stimulation caused a small but insignificant rise in hPP concentration. Phentolamine alone caused a twofold rise in hPP concentration, which was abolished by simultaneous atropine infusion. Propranolol alone had no effect. Adrenergic beta-receptor stimulation with epinephrine plus phentolamine caused a sevenfold rise from 45 +/- 10 to 351 +/- 60 pM (P < 0.05), whereas adrenergic alpha-receptor stimulation caused a significant fall from 100 +/- 25 pM (the rise in hPP concentration induced by epinephrine) to 44 +/- 7.8 pM. The changes in hPP concentration did not correlate with changes in serum insulin, glucose, or free fatty acid (FFA) concentrations. The pattern of the response was quite different from insulin, while reached a peak within 1 min of phentolamine administration, whereas hPP levels rose slowly to a peak at 45 min. The rise induced by adrenergic beta-receptor stimulation with epinephrine plus phentolamine was equivalent to the rise from 40 +/- 11 to 280 +/- 48 pM caused by an insulin-induced fall in serum glucose of about 50% and that induced by isoproterenol infusion, which caused a fourfold rise from 69 +/- 3 to 271 +/- 84 pM. These data suggest that the adrenergic system may be important in the regulation of hPP release.

The effect of dietary fiber on glucose and hormone responses to a mixed meal in normal subjects and in diabetic subjects with and without autonomic neuropathy.

We investigated the effects of fiber on responses of blood glucose, serum insulin, gastric inhibitory polypeptide (GIP), and immunoreactive pancreatic glucagon (IRG) to ingestion of mixed meal with and without added fiber (5 g guar and 5 g pectin) in 12 normal, healthy subjects and in 12 age-, sex-, and weight-matched non-insulin-dependent, maturity-onset diabetic subjects (NIDDM). Fiber markedly enhanced glucose tolerance in the normal subjects without a change in insulin or GIP but with a significant reduction in glucagon responses. Fiber also markedly improved glucose tolerance in the NIDDMs without changing insulin or GIP but with a significant reduction in the glucagon responses. The NIDDMs were divided into two groups of six subjects, with and without autonomic neuropathy (AN). In NIDDMs without AN, glucose tolerance was improved by fiber without a change in insulin, IRG, or GIP. In diabetic subjects with AN, glucose tolerance was not improved, although glucagon levels were lowered and insulin and GIP responses were unchanged. It appears, therefore, that fiber improves glucose tolerance by altering factors other than insulin. It seems also that autonomic nervous supply to the gastrointestinal tract is important in mediating the effect.

Plasma pancreatic polypeptide concentrations in acute pancreatitis.

Plasma human pancreatic polypeptide (hPP) concentrations were measured in 17 patients with acute pancreatitis. On admission the mean plasma hPP concentration was 33 +/ 6,9 pmol/l (range 11-92 pmol/l), which was similar to the mean hPP concentration of 43 +/- 4 pmol/l (range 11-92 pmol/l) in age-matched healthy subjects. The plasma immunoreactive glucagon (IRG) concentration was elevated 5-fold. Nine patients were managed conventionally and received prolonged glucagon infusion, and 8 were managed conventionally and received saline infusion. Treatment was carried out in a double-blind manner. Glucagon infusion caused a further 5-fold rise in circulating IRG concentrations and an increase in the blood glucose concentration from 7,5 to 9,7 mmol/l. This was associated with a fall in hPP concentrations and a significant reduction in variability. It is suggested that plasma hPP levels are not elevated in patients with acute pancreatitis and, therefore, do not reflect acute pancreatic damage.

Synthetic luteinizing hormone-releasing hormone in impotent male diabetics.

We compared the effect of luteinizing hormone-releasing hormone (LH-RH) 500 micrograms 8-hourly and placebo on sexual function in impotent diabetic males. These patients had no obvious vascular or neurological disease and no major psychological disorders to account for their impotence. Basal serum testosterone concentrations were normal in all. Five patients had elevated basal gonadotropin concentrations and/or exaggerated gonadotropin responses to LH-RH. During the first week of the LH-RH treatment there was a significant rise in LH and follicle-stimulating hormone (FSH) concentrations. The LH levels remained elevated throughout the second week of treatment, whereas the FSH returned to pretreatment values. There was no change in hormone concentration during placebo therapy. Clinical responses to treatment were assessed by a self-evaluating questionnaire relating to (i) sexual function and libido; (ii) erectile potency; and (iii) general well-being. There was no significant change within each category, but taken together a significant improvement was found with both LH-RH and placebo treatment. There was no difference between the two forms of treatment.

Pancreatic polypeptide (PP) responses to oral and intravenous glucose in man.

Serum human pancreatic polypeptide (hPP) responses to 50 gm. of oral glucose and a 25 gm. intravenous bolus of glucose were measured in 10 healthy human volunteers. Oral glucose caused a 50% rise, whereas I.V. glucose caused a 35% fall in hPP concentration. There was no relationship between the absolute glucose concentration or the change in glucose level and the PP concentration. It is suggested that oral and I.V. glucose affect PP by indirect mechanisms and that PP may be involved in carbohydrate metabolism in man.