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Biomedical subjects

M H Golden

Publications and source records attributed to M H Golden.

At least 37 records · Page 2Linked to original sources

Electrophysiological assessment of brain function in severe malnutrition.

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.

Body Height↗

Glyoxalase I activity in erythrocytes from severely malnourished children.

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.

Child↗

Micronutrient status of the besieged residents of Sarajevo: May 1993.

OBJECTIVE: To assess micronutrient status indices in blood and plasma of subjects subjected to siege conditions. DESIGN: Whole blood and serum samples were taken from subjects, sampled from 30 clusters in four Municipal Areas of Sarajevo. The blood samples were flown, under appropriate refrigeration, to the UK for analysis. SETTING: The study was conducted in besieged Sarajevo and laboratory analyses were carried out at Department of Clinical Chemistry, Aberdeen Royal Infirmary and at Rowett Research Institute, Aberdeen, Scotland. SUBJECTS: 202 subjects, aged from 1 to 82 years were included in the sample. INTERVENTIONS: Serum folate, ferritin, transferrin, retinol, retinol-binding protein, beta-carotene, alpha-tocopherol, 25-hydroxycholecalciferol, C-reactive protein, haemoglobin and mean corpuscular volume of blood were determined. Micronutrient status was assessed by comparison with a range of values derived from multinational data sets from both pathologically malnourished and normal subjects. RESULTS: Haemoglobin, ferritin, folate, retinol and 25-hydroxycholecalciferol levels were lower in the Sarajevan sample than in normal reference populations. Serum alpha-tocopherol was low in children and adolescents while a low beta-carotene level probably reflected the scarcity of green vegetables. No consistent evidence of protein/energy deficits were detected. CONCLUSIONS: Data for retinol binding protein and transferrin, when considered in association with BMI and Z-score data, provided no significant evidence of protein-energy undernutrition. However, the prevailing food aid rations failed to maintain adequate reserves of several micronutrients, particularly iron, folate and vitamin D. The significance of low values for serum retinol and beta-carotene and of low serum alpha-tocopherol in children must be investigated further.

Adolescent↗

Production of interleukin-6 and tumour necrosis factor-alpha in vitro is reduced in whole blood of severely malnourished children.

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.

Female↗

The effect of acidosis on the labelling of urinary ammonia during infusion of [amide-15N]glutamine in human subjects.

In three experiments [amide-15N]glutamine was infused intravenously in male volunteers. After 4-8 h of infusion acidosis was achieved by an oral dose of CaCl2 (1 mmol/kg). In one subject acidosis was maintained for 5 d. The acid load produced an approximately 3-fold increase in urinary NH3 excretion, with a small (approximately 20%) and transient increase in the isotope abundance of urinary NH3. Estimates of glutamine production rate (flux) were obtained in two experiments. There was no evidence that it was increased in acidosis. The extra NH3 production by the kidney represented only a very small part, about 3%, of the total glutamine production rate.

Acidosis↗

Pathology of the lungs in childhood malnutrition in Jamaica. Light and electron microscopy.

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.

Female↗

Serum inorganic phosphate in protein-energy malnutrition.

We retrieved a series of measurements made 35 years ago of the concentration of inorganic phosphate (P) in the serum from 56 cases of severe protein-energy malnutrition at the Tropical Metabolism Research Unit, Jamaica. There is no record of whether or not the cases were randomly selected. The samples were obtained within 4 days of admission and except in 3 cases there was no follow-up. The average age was 12 months. The children have been classified retrospectively from the notes as marasmus (11 cases), kwashiorkor (22 cases) and marasmic kwashiorkor (23 cases). In all 11 children died (fatality rate 20%), eight of them from the group with marasmic kwashiorkor. Weight-for-age, length-for-age and weight-for-length have been calculated as Z-scores. Nearly all serum phosphate concentrations were low (mean 1.41 mmol.l-1, SD 0.444, range 0.50-2.45) compared with the normal value at this age of about 2 mmol.l-1. The serum P was significantly less depressed in the marasmic children (P = 0.042), but there was no relation between serum P and any of the anthropometric measurements, nor with outcome (death or survival). There was, however, a significant relationship with the degree of oedema. Death was related to age--the children who died were younger (mean difference 3.8 months; P = 0.01; 95% confidence interval 0.23-6.43). It took about 3 weeks of feeding a milk-based diet for serum phosphate to reach normal levels. There have been few previous measurements of serum P in malnutrition.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗

Is complete catch-up possible for stunted malnourished children?

Although malnourished children are stunted, their bone maturity is usually retarded to a comparable degree. This is seen in impoverished societies as well as in diseases such as coeliac disease, inflammatory bowel disease and hormonal deficiency. When these children are followed to adulthood they normally have some degree of spontaneous catch-up. With a change in environment, through adoption, emigration or with treatment of the disease there is usually definite catch-up growth, although it is often not to the NCHS standards. If puberty is delayed and/or growth continues into the early or mid twenties, then an acceptable final adult height is achieved. However, there may be a limitation imposed on an individual's maximum height by genetic imprinting in very early development. This may be the case where full catch-up appears to have taken place but is followed by an advanced puberty and early cessation of growth (Proos, Hofvander & Tuvemo, 1991a). The data from US slaves and cases of hormonal replacement, where treatment was initiated after age 18, each show that, if the circumstances of children in the Third World change, almost complete reversal of stunting is possible. The children can reach their own height potentials. Total reversal to affluent societal norms would probably require cross-generational catch-up. The most obvious reason why catch-up is not seen regularly is that an appropriate diet is not available over a sufficient period of time. We do not know the optimum ingredients for such a diet. Sulphur has been neglected as an essential nutrient; its economy should be examined in relation to skeletal growth in stunted populations.

Adolescent↗

Peroxisomes and the hepatic pathology of childhood malnutrition.

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.

Biopsy↗

Acute-phase protein response is impaired in severely malnourished children.

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.

Acute Disease↗

Elevated glutathione S-transferase activity in erythrocytes from malnourished children.

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.

Age Factors↗

Ultrastructure of the islets of Langerhans in protein-energy malnutrition.

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.

Female↗