Nutritional associations with bone loss during the menopausal transition: evidence of a beneficial effect of calcium, alcohol, and fruit and vegetable nutrients and of a detrimental effect of fatty acids.

BACKGROUND: The menopausal transition is characterized by rapid bone loss. Few data exist on the role of nutrition. OBJECTIVE: The objective of the study was to ascertain which dietary factors influence perimenopausal skeletal loss. DESIGN: A longitudinal study was conducted of 891 women aged 45-55 y at baseline and 50-59 y at follow-up 5-7 y later. Bone mineral density (BMD) was measured by using dual-energy X-ray absorptiometry at the lumbar spine and femoral neck (FN). Nutrient intakes were assessed after the baseline visit and 5 y later, by using the same food-frequency questionnaire. RESULTS: After adjustment for energy intake and other confounders, higher intakes of calcium were correlated with change in FN BMD (ie, reduced loss) (r = 0.073, P < 0.05), and the intake of modest amounts of alcohol was associated with less lumbar spine bone loss (P < 0.01 for quartile of alcohol intake). Greater FN BMD loss was associated with increased intake of polyunsaturated fatty acids (r = -0.110, P < 0.01), monounsaturated fatty acids (r = -0.069, P < 0.05), retinol (r = -0.067; P < 0.05), and vitamin E (r = -0.110; P < 0.01). The latter 2 nutrients were highly correlated with polyunsaturated fatty acids. For premenopausal women, calcium and nutrients found in fruit and vegetables (vitamin C, magnesium, and potassium) were associated with FN BMD, and calcium, vitamin C, and magnesium were associated with change in FN BMD. CONCLUSIONS: Although menopausal status and hormone replacement therapy use dominate women's bone health, diet may influence early postmenopausal bone loss. Fruit and vegetable intake may protect against premenopausal bone loss.

Antenatal factors in the development of the lumbar vertebral canal: a magnetic resonance imaging study.

STUDY DESIGN: The lumbar vertebral canal was measured in two cohorts of 10-year-old children (n = 161) using magnetic resonance imaging (MRI) and compared with obstetric records. OBJECTIVE: To investigate whether there are identifiable obstetric factors that determine the size of the lumbar vertebral canal. SUMMARY OF BACKGROUND DATA: The most rapid period growth for the lumbar vertebral canal is between 12 and 32 weeks in utero, with the midsagittal diameter of L1-L4 already 70% of adult dimension at birth. Therefore, adverse antenatal factors during this critical growth period may be expected to affect the size of the canal. METHODS: The canal size was measured from axial MRI sections taken through each lumbar vertebra (L1-L5) at the pedicular level of 84 children. Relations with obstetric data, prospectively collected in a neonatal database, were sought. The relation of low birthweight and canal size was further investigated in a second cohort of children (n = 77). RESULTS: The canal size, particularly the midsagittal diameter and the cross-sectional area, was found to be significantly reduced by low birthweight (with growth retardation in utero being a more important factor than length of gestation), low placenta weight, and lower socioeconomic class. Smoking during pregnancy significantly reduced the perimeter at L3 (P = 0.032) and L5 (P = 0.031), and also the cross-sectional area at L3 (P = 0.030) and L5 (P = 0.016). CONCLUSIONS: This study showed that, for this group of children, the size of the lumbar vertebral canal was reduced by low birthweight, with maternal smoking as an added adverse factor. Therefore, good antenatal care and maternal education may help to reduce the risk of spinal stenosis in adult life.

Urinary collagen cross-links as biochemical markers of growth: an evaluation of biological variables.

AIM: To investigate the validity of urinary pyridinium cross-links (pyridinoline and deoxypyridinoline) as markers of growth in healthy children. METHODS: Three pilot studies (P1-P3) were conducted to investigate the time of day, the minimal duration within a day, and how many times per week urine samples needed to be collected to obtain representative values of cross-link excretion in normal children 3-5 years of age. The results were used to design a 4-month longitudinal protocol to evaluate whether pyridinium cross-links could be used as markers of growth velocity. RESULTS: Mean differences from 24-hour values were only between 1 and 4% for urinary cross-links (nmol/h) in overnight 12-hour collections. Three consecutive collections were required for weekly output estimates with a maximum error of 10% in >90% of the children. During the 4-month longitudinal study, the regression equation of height velocity on pyridinoline and deoxypyridinoline excretion explained approximately 60% of the variance in the subgroup of subjects who provided three complete urinary collections per observation period. No relationship was observed when the cases with fewer or incomplete collections were included in the analysis. Cross-link values collected at baseline were of no use to predict height velocity at 4 months. CONCLUSIONS: Urinary pyridinium cross-links correlate with the growth velocity in healthy children when using an appropriate urinary collection protocol. However, their predictive value in this population is negligible.

Glyoxalase I activity in erythrocytes from severely malnourished children

The enzyme glycoxalase 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 therfore assayed in erythocytes taken from 133 severely malnourished children and 21 age-matched controls. The mean values (ñSEM) for the marasmic group (marasmus: 105 ñ 4/u/gm Hb) and the group with kwashiorkor (Kwash: 103 ñ 4/u/gm Hb) were not significantly different from controls (cont: 104 ñ 2u/gm HB)>. In the group with marasmic-kwashiorkor (M-K: 88 ñ 4u/g Hb) Glyox I activity was significantly lower 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 per cent 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

Glyoxalase I activity in erythrocytes from severely malnourished children

The enzyme glycoxalase 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 therfore assayed in erythocytes taken from 133 severely malnourished children and 21 age-matched controls. The mean values (ñSEM) for the marasmic group (marasmus: 105 ñ 4/u/gm Hb) and the group with kwashiorkor (Kwash: 103 ñ 4/u/gm Hb) were not significantly different from controls (cont: 104 ñ 2u/gm HB)>. In the group with marasmic-kwashiorkor (M-K: 88 ñ 4u/g Hb) Glyox I activity was significantly lower 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 percent 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 (AU)

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 kwashiokor (23 cases). In all 11 children died (fatality rate 20 percent), 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.1-1, SD 0.444, range 0.50-2.45) compared with the normal value at this age of about 2 mmol.1-1. 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 percent 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. We agree with previous authors that the low serum values are evidence of phosphate depletion and suggest that phosphate might be added to the electrolyte solutions used in the early stages of recovery. However, reports of adverse effects indicate that this should be done with great care (AU)

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 per cent of cases. An additional 18 per cent showed bronchitis, bronchiolitis or interstitial pneumonitis. Aspiration of gastric contents was evident in 10 per cent of cases; 6 per cent showed pulmonary oedema and congestion. In the remaining cases, no lung pathology was identified (17 per cent ). 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 pnuemocytes. Useful information can be obtained on the fine structure of the lung, using samples taken soon after death.

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 percent of cases. An additional 18 percentshowed bronchitis, bronchiolitis or interstitial pneumonitis. Aspiration of gastric contents was evident in 10 percent of cases; 6 percent showed pulmonary oedema and congestion. In the remaining cases, no lung pathology was identified (17 percent). 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 pnuemocytes. Useful information can be obtained on the fine structure of the lung, using samples taken soon after death. (AU)

Peroxisomes and the hepatic pathology of childhood malnutrition

Liver specimens obtained immediately after death from eight severly malnourished children were examined by electron microscopy, and compared with seven liver biopsy specimens from children who 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 reducation 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 peroximes 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 electrolyted into the cell.

Peroxisomes and the hepatic pathology of childhood malnutrition

Liver specimens obtained immediately after death from eight severly malnourished children were examined by electron microscopy, and compared with seven liver biopsy specimens from children who 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 reducation 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 peroximes 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 electrolyted into the cell (AU)

Coagulase-negative staphylococcal bacteraemia in severely malnourished Jamaican children - abstract

Immunosuppression increases the susceptibility to infection and changes the inflammatory response in children with severe protein-energy malnutrition. In this five-year prospective study, bacteraemia was documented in 16 percent of 336 severely malnourished children (2-34 months of age), who were hospitalized consecutively in the Tropical Metabolism Research Unit, UWI, Kingston, Jamaica. The fifty-three children had 60 episodes of noscomial and community-acquired bacteraemia with 69 blood isolates. Community-acquired bacteraemia accounted for 72 percent (43/60) of bacteraemic episodes. Thirty-five per cent (24/69) of the strains were coagulase-negative staphylococci, 19 percent (13/69) were Staphylococcus aureus and 11 percent (8/69) were Streptococcus Group D. Seventeen episodes of coagulase-negative staphylococcal bacteraemia were acquired in the community, and seven were nosocomial. These patients were more likely to have pneumonic consolidation than children with all other bacteraemias combined (p<0.02, Fisher Exact Test). The bacteraemia-related case fatality rate was 8 percent (5/60). Polymicrobial and gram-negative septicaemia were independent positive predictive factors for mortality when compared with single-agent and gram-positive sepsis (p<0.02). This 71 percent (49/69) prevalence of gram-positive organisms suggests a change in the epidemiology from the predominant gram-negative aetiologies described in previous reports (AU)

Elevated glutathione S-transferase activity in erythrocytes from malnourished children

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)

Comparison of antioxidant status during recovery from malnutrition on a corn oil- or coconut oil-based diet - abstract

Children recovering from malnutrition are given a high-energy diet during the "catch-up" phase. Corn oil, a poly-unsaturated fatty acid (PUFA) rich vegetable oil, is used to supply 60 per cent of the energy in the recovery diets. Previous work suggests that this high intake of corn oil may be associated with a deterioration of antioxidant status. A normal antioxidant status is essential for protection against cell damage. We therefore compared indices of antioxidant status (whole blood gluthathione, GSH; plasma vitamen E; and urinary mercapturic acid outputs (UMCA) in two groups of malnourished children who had recovered on isocaloric diets containing either PUFA rich, corn oil (Control group) or coconut oil (test group), which is rich in saturated fatty acids. Both groups showed an initial normalisation of GSH and vitamin E levels; whereas the test group maintained normal levels, the control group showed a progressive decrease of both indices during recovery. At discharge the test group had GSH (2.7 ñ 0.08 vs 2.44 ñ 0.88 mmol/Lrbc, mean ñ SEM) and vitamen E (8.44 ñ 1.21 vs 7.38 ñ 1.01 mg/l), levels that were significantly higher (p< 0.05) that in the Control group. Several children in the Control group had vitamen E levels that were below the accepted normal range. At recovery, UMCA outputs of the Control group (4.85 ñ 0.55 umol/kg/24 hr) were further increased, and as such were significantly higher (p < 0.05) than the admission mean (3.32 ñ 0.54 umol/kg/24 hr). In the test group, mean discharge UMCA output (1.98 ñ 0.44 umol/kg/24 hr) was significantly lower than admission values, as well as the mean discharge UMCA output of the Control group. This suggests that the body's burden of compounds that require detoxification is significantly increased when malnourished children are rehabilitated on a diet rich in corn oil. Following recovery on the coconut oil diet, plasma cholesterol levels (2.30 ñ 0.15 mmol) were similar to the pre-treatment mean (2.15 ñ 0.11 mmol). However, plasma levels of triglycerides fell significantly (p < 0.05) with treatment (pre: 1.23ñ0.14; post 0.88ñ0.08 mmol). When given a diet that is not rich in PUFA, malnourished children are able to maintain their antioxidant status within the normal range. It is suggested that coconut oil be used routinely in the formulation of recovery diets for malnourished children (AU)

Acute-phase protein response is impaired in severely malnourished children

The reponse of plasma levels of C-reactive protein and serum amyloid A were assessed in two groups of malnourished children. 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 percent) and serum amyloid A was not raised in 29 (58 percent) of these 50 children. 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. 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 midly malnourished group was no different from that of the severely malnourished group in early recovery, but was less than their response on discharge. The acute-phase protein response of malnourished children is impaired. This may have prognostic implications as the reponse plays a central role in promoting healing. (Summary)

Coagulase-negative staphylococcal bacteremia in severely malnourished Jamaican children

Immunosupression 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 percent of the 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 percent (43 of 60) of bactermic episodes. Thirty-five percent (24 of 69) of the strains were coagulase-negative staphylococci, 19 percent (13 of 69) were Staphylococcus aureus and 11 percent (8 of 69) were Streptococcus Group D. Seventeen episodes of coagulase negative staphylococcal bacteremia were acquired in the community and 7 nosocominal. 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 percent (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 percent (49 of 69) prevalence of Gram-positive organism suggests a change in the epidemiology from the predominant Gram-negative etiologies (76 percent) described in previous reports (AU)

Hepatic ultrastructure in children with protein-energy malnutrition

Samples of liver from eight children who died from malnutrition with its complications were studied by electron microscopy. Specimens were taken within one hour of death. These tissues had changes consistent with severe terminal illness, including mitochondrial swelling, with loss of matrix granules, disorganization of cristae, and evidence of calcium influx. Glycogen tended to be scanty. Lipid droplets were frequent. Endoplasmic membranes were depleted, and focal cytoplasmic degradation was frequent. Intracanalicular cholestasis was striking in four cases with loss of microvilli. Peroxisomes were depleted. This may be significant as peroxisomes are pivotal in the processing of very long-chain fatty acids in cholic acid metabolism and in elimination of free radicals. The observations were compared with previous reports in the literature, and with seven biopsies taken in 1970 from malnourished children who recovered. One, obtained on the fourth day, from a child with marasmus, showed atrophy of cellular organelles. The other samples were biopsied during the recovery phase, and displayed considerable restoration to normal morphology. Mitochondria had prominent matrix granules. Peroxisomes were frequently seen. There was no evidence of cholestasis (AU)

Ultrasonographic assessment of the extent of hepatic steatosis in severe malnutrition

Ultrasonographic, blinded assessment was made of the extent of hepatic steatosis in 55 children with severe malnutrition: undernutrion (n=6), marasmus (n=18), marasmic-kwashiorkor (n=17), and kwashiorkor (n=14). The children were examined on admission, in early recovery (considered as baseline), and again 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 ñ 0.3 percent/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 under-nourished children. Its extent is not necessarily related to the degree of hepatomegaly and accumulated lipid is only slowly mobilised (AU)

Effect of zinc on lean tissue synthesis during recovery from malnutrition

During recovery from severe wasting, malnourished children gain weight at greatly accelerated rates. To determine if additional zinc added to their basal therapeutic diets increased the retention of lean tissue and stimulated protein metabolism, we studied three groups of children taking either the basal diet alone or the basal diet supplemented with either 76 mumol (5 mg) or 153 mumol (10 mg) Zn/kg diet. The zinc-supplemented children gained similar weight and consumed the same amount of diet as the unsupplemented children. Zinc supplementation resulted in a greater net absorption of nitrogen and a higher rate of protein turnover, as estimated from urinary ammonia 15N enrichment after oral [15N] glycine. We conclude that additional zinc affected the composition of newly synthesized tissue and intermediary nitrogen metabolism (AU)

The exocrine pancreas in kwashiorkor and marasmus. Light and electron microscopy

Histological sections of pancreas and liver from 65 cases of children dying from childhood malnutrition were reviewed. The extent of pancreatic atrophy and fibrosis was compared with fatty change in the liver. Pancreatic atrophy was common, and often associated with severe fatty change in the liver, but also occurred in marasmic children with scanty liver fat. Pancreatic fibrosis, when present, was only of mild degree. Among 16 patients with marasmus, fibrosis was only seen in one pancreas. Fibrosis was recorded in 8/25 cases of kwashiorkor, and in 7/24 cases diagnosed as marasmic-kwashiorkor. Electron microscopy of the pancreas was performed in seven cases, using tissue collected at immediate autopsy. Atrophy and variable amounts of degranulation of acinar cells were seen. There was often disorganization of the endoplasmic reticulum with intracisternal sequestration. Mitochondrial swelling was consistent with terminal anoxia. Centro-acinar cells were prominent. Some acini were dilated and contained fibrillar material. These findings support the pioneer paper by Blackburn and Vinijchaikul (1969) and underlie the importance of pancreatic atrophy in the pathology of protein-energy malnutrition.