Cholesterol regulates the cell surface expression of glycophospholipid-anchored CD14 antigen on human monocytes.

The CD14 antigen which is expressed on human monocytes and macrophages is a phosphatidylinositol-linked surface protein. We investigated the effects of cellular cholesterol depletion and repletion on cell surface expression of this glycoprotein. Adherent normal human monocytes were cultured for four days in media containing delipidated fetal calf serum which depleted cellular cholesterol. Immunofluorescence analysis demonstrated a markedly diminished surface expression of CD14 on cells cultured in delipidated serum compared to normal serum. Expression of CD64 (high-affinity Fc receptors, Fc gamma RI) also was reduced under these conditions. This inhibition of CD14 expression was overcome by addition to the culture medium of cholesterol, low density lipoprotein, or very low density lipoprotein. All of these supplements replenished cellular cholesterol. Expression of CD64(Fc gamma RI) was not restored by addition of cholesterol. These observations indicate that cholesterol can regulate the surface expression of some phosphatidylinositol-anchored glycoproteins.

Aetiopathology and genetic basis of neonatal diabetes.

A British Paediatric Association Surveillance Unit* study of neonatal diabetes determined a national incidence of 1 in 400,000 live births. Additional cases of transient neonatal diabetes were collected retrospectively. Most cases were of low birthweight at term: none had evidence of an autoimmune aetiopathogenesis. The median requirement for exogenous insulin treatment was three months. A significant number of cases developed type 2 diabetes in later life. Three of the 11 cases were found to have paternal uniparental isodisomy of chromosome 6. A further patient carried an unbalanced duplication of 6q 22-23, inherited from the father, which localised a potentially imprinted gene for diabetes to this region. The fact that low birthweight predisposes to type 2 diabetes in later life is well established, but a genetic defect that may relate both to intrauterine growth failure and the development of type 2 diabetes in later life has now been identified.

Urinary heparan sulphate proteoglycan excretion is abnormal in insulin dependent diabetes.

Urinary excretion of heparan sulphate proteoglycan (HSPG), the main anionic component of the glomerular basement membrane (GBM), was estimated in 30 adolescents and young adults with insulin dependent diabetes (IDDM), 10 with microalbuminuria and 20 sex matched, diabetic controls of similar age without evidence of microalbuminuria. A further 10 non-diabetic control subjects were also examined. Both groups of patients with diabetes had significantly elevated excretion of HSPG when compared to normal individuals. There was no difference in HSPG excretion between diabetic subjects with and without microalbuminuria.

The risk of diagnostic radiation of the newborn.

The amount of diagnostic radiation received by neonates at a large maternity hospital in 1982 was calculated. The risk of inducing neoplasia is unlikely to be greater than one in 280,000 for each radiograph of chest or abdomen. Provided that the exposure of the newborn to radiation at the John Radcliffe Hospital is typical of the rest of the country, and excluding cardiac catheterisation and computed tomography, we estimate that at most one to two cases of malignant disease per year may be caused by diagnostic radiation in the United Kingdom. Genetic risks appear to be negligible. The risks of not using radiography in newborn patients outweigh the risks of inducing malignant or genetic disease.

Preterm milk.

PIP: This editorial addresses the question of how best to feed the low birth weight infant. A study by Atkinson et al. on the composition of preterm mothers' milk found the nitrogen concentration in preterm milk to be considerably higher than in term milk. Preterm milk may be uniquely suited to the growth requirements of preterm infants. With the exception of calcium and phosphorus, preterm milk fits the requirements for preterm infant growth. Because of the difficulties of sustaining lactation without the infant sucking at the breast, partly due to the mother's motivation in the face of all the difficulties of having a baby in a Special Care Baby Unit, and partly due to the associated socioeconomic disadvantages, it is not possible for all mothers who deliver preterm babies to sustain their lactation. The composition of preterm milk should be used as a guide for the preparation of a human milk formula built from human milk products from a milk bank. The development of a human milk formula must take into account variations in the absorption of nutrients in low birth weight infants which may be affected by the processing of the milk, and variations in fat absorption in preterm infants which occur even when they are fed their mothers' fresh unprocessed milk.^ieng

The nipple-shield sampling system: a device for measuring the dietary intake of breast-fed infants.

We have devised a method for the determination of the composition of the milk infants obtain from the breast during suckling itself, suckled breast milk (SBM). The method involves the use of a nipple-shield sampling system, together with data on the pattern of milk flow from mother to infant derived from a cross-sectional analysis of test weighings during feeding. In this study, marked changes were demonstrated in milk fat the sixth day postpartum. From this information the total intake of fat and energy during the feed was calculated. These preliminary findings suggest that published information on the dietary intake of breast-fed infants may need some revision.

The biology of human drip breast milk.

The milk which drips from the opposite breast during breast feeding is used in some centres for feeding premature babies, yet there is little scientific information on the biology of this secretion. Drip breast milk (DBM) differs from expressed breast milk (EBM), both in its contents and in the change in its composition over the period of lactation. The fat concentration and energy value of DBM are low, compared with levels reported for EBM: protein, fat, sodium and energy value in DBM fall with the duration of lactation, whereas magnesium and calcium rise, and lactose, potassium osmolality and lysozyme remain constant. The milk fat content of DBM produced by individual donors is linearly related to the daily volume of DBM produced. Studies on 477 women admitted to the Oxford General Practice Obstetric Unit over 1 yr showed that, of the 75% who were lactating successfully 2 wk after delivery, 19% were producing DBM by 2--4 wk. Women who produced DBM did not differ in age or parity from those lactating women who did not, and their babies did not differ in birthweight, gestation, centile or sex. The suitability of DBM as a food for premature infants is discussed.

Differences in the pattern of milk intake between breast and bottle fed infants.

Two hundred and nine 6-day-old healthy term infants were test weighed either during bottle feeding (n= 77) or breast feeding (n=132). Cross-sectional data collection avoided repeated interruptions of individual feeds. Bottle fed infants (fed ad libitum) and breast fed infants consumed a similar feed volume (respectively, 67 +/- 2 ml versus 75 +/- 6ml, mean +/- S.E.M.) over a similar period of time (mean 25 min); yet the pattern of milk flow during feeding was significantly different in the two groups. In bottle fed infants, there was a linear pattern of milk intake over the first 10 min of feeding, by which time 81% of the feed has been consumed, contrasting with a biphasic intake pattern in breast fed infants in whom a total 84% of the feed was consumed either in the first 4 min or between 15 and 19 min after the start of the feed. It is speculated that these differences in the pattern of milk intake could influence the physiological responses to feeding and might account for differences between breast and bottle fed infants in gut hormonal responses to milk feeds.

Effect of a traditional and of a new nipple shield on sucking patterns and milk flow.

The effect of a traditional (Mexican Hat) and of a new (Thin Latex) nipple shield on the sucking patterns and milk intake of 5-8-day-old babies was examined. Milk intake was determined accurately by test weighing using a Sartorius electronic balance with animal weighing keyboard, and sucking patterns by filming the mouth of the baby. The Mexican Hat reduced milk transfer by 58% (P is less than 0.01), and increased sucking rate (P is less than 0.05) and time spent resting (P is less than 0.01). The Thin Latex nipple shield reduced milk intake by a smaller amount (22%), and had no significant effect on sucking patterns.

The water content of the human umbilical cord.

105 umbilical cords from 53 term and 52 preterm newborn infants were freeze-dried after removal of the blood vessels, to determine the water content. The mean umbilical cord water content (i.e. mean of water content of fetal and placental ends of the cord), was 88.9% (SD 2.73) for term cords and 91.9% (SD 1.99) for preterm cords. The mean water content fell with increasing gestation. The fetal end of the cord had a significantly higher water content than the placental end. Similarly, the volume of a 4-cm length segment of cord was significantly greater at the fetal than placental end. There was no correlation between cord water content or volume and several other variables including birthweight, size for gestational age and placental weight. These observations suggest a metabolically active role for the umbilical cord.

Individual patterns of milk intake during breast-feeding.

The pattern of milk transfer during breast-feeding was ascertained for individual mother-infant pairs using a 'fractional' weighing technique. This method employs a single, fixed intermediate weighing on each breast, and a flexible, final weighing point at the 'natural' termination of feeding on each breast. The data demonstrate considerable variability between individuals both in feed length and in the rate of milk transfer from mother to baby. They show that the rate of intake tends to be consistent between the first and second breast, and that each mother-infant pair has a characteristic rate of milk transfer. Significant milk intake occurred from four minutes to the end of the feed on each breast. These results imply that breast-feeding 'rules' about the length of a feed can only be offered as helpful guidelines, rather than principles to be strictly followed. The results of a reciprocal nursing experiment suggest that the typical rate of milk transfer is a product of both milk release by the mother and milk demand by the baby.

Paediatric preparation for multiple premature births.

We describe the managment of 2 sets of pre-term quadruplets born to 2 women pregnant concurrently following the induction of ovulation with gonadotrophin. Careful antenatal planning was necessary to provide for each of the 8 pre-term infants a standard of neonatal medical and nursing care comparable to that normally available for singleton pre-term infants.

A human milk formula.

In view of the possible deficits in the energy value and protein content of human milk when used for feeding low birth weight preterm neonates, a method has been devised suitable for use in a human milk bank for making milk formulae from human milk products. Human milk formula (HMF) is produced by adding, to whole human milk, human cream, obtained by separation by centrifugation, together with salt-free and lactose-free human milk protein, extracted by simple dialysis and freeze-drying. This human milk formula is, therefore, enriched in energy, human milk fat, protein and salts (which may be added), to approach the current concept of an ideal milk formula(e) for preterm infants. In addition, the increased concentration of antimicrobial proteins achieved in HMF may offset any losses in these proteins caused by pasteurisation.

The continuous measurement of milk intake at a feed in breast-fed babies.

A method for the continuous measurement of milk intake during a breast-feed is described. A miniature Doppler ultrasound flow transducer, located in the tip of a latex nipple shield, is interposed between mother and baby during feeding. Preliminary results indicate the scope and current limitations of the method in terms of both populations and individual mother/infant pairs. An initial analysis of individual feeds indicates that two factors may contribute to the curtailment of intake during a feed from one breast: a progressive reduction in intake volume per suck, and/or an increase in the proportion of time spent pausing between bursts of sucking.

Short-time low-temperature pasteurisation of human milk.

Using the Oxford Human Milk Pasteuriser human milk was exposed to lower temperature and shorter time periods than employed in classical holder pasteurisation. Heating human milk at 62.5 degrees C for 5 min completely destroyed Escherichia coli, Staphylococcus aureus, and group B beta-haemolytic streptococci inoculated into the samples. Heating at 56.0 degrees C for 15 min destroyed over 99% of the inoculated organisms. The mean percentage remaining activity of certain antimicrobial proteins after heat treatment at 62.5 degrees C for 30 min, 62.5 degrees C for 5 min and 56 degrees C for 15 min were as follows: IgA 67, and 90%; lactoferrin 27, 59 and 91%; and lysozyme 67, 96 and 106%, respectively. These results suggest that human milk can be effectively pasteurised using less heat treatment than in classical holder pasteurisation. Lower temperature and shorter heat treatment also preserves substantially more of the activity of the antimicrobial proteins present in human milk.

Drip breast milk: it's composition, collection and pasteurization.

"Drip breast milk" is that milk which spontaneously drips from the contralateral breask during the suckling of an infant. Biochemically and immunologically, pooled drip milk resembled pooled mature expressed breast milk, although it has a lower fat concentration. About 15% of lactating women are capable of producing drip milk; volumes produced are up to 188 ml/donor/day. A milk bank is described which processes 1400 liters of drip milk/yr. Heat treatment of this milk with a semi-automated holder pasteurizer caused a 21% reduction in IgA concentration and a 36% reduction in lysozyme activity, as well as a decrease in the ability of the milk to inhibit the growth of E. coli. In comparison with boiling, pasteurization was as effective in reducing total bacterial content provided the milk initially contained fewer than 10(6) bacteria/ml.

Evaluating breast-milk intake by test weighing: a portable electronic balance suitable for community and field studies.

A K-Tron Digital Scale (Model DS-1) was used to weigh a group of 52 new born babies. The regression of the weights on true weights obtained with a Sartorius electronic balance 3806MP was 0.9911, with an estimated residual variance of 5.25. With the same babies weighed on a Marsden Weighmaster, the estimated residual variance was 68.93. Data from published studies on other balances are presented for comparison. The K-Tron is a reliable, portable, battery operated balance suitable for measuring milk intake by test weighing in homes or in the field.

The automatic sampling shield: a device for sampling suckled breast milk.

The automatic sampling shield uses the negative pressure exerted by the breast-feeding baby during sucking to withdraw a series of small samples from the milk stream. Shield performance was studied at four feeds for each of 13 babies. Acceptance of the shield was good (96% of feeds) and samples were obtained in 88% of feeds. Sample weight was large enough for micro-biochemical analysis of composition (median weight 1.3 g), without depriving the baby of important amounts of milk (median percentage of weight of milk intake was 4.3% and sample weight was less than 5 g in all cases). The shield should sample a constant proportion throughout the feed, in order to obtain a sample that is representative of the infant's nutrient intake. Fractional test-weighing of feeds showed a tendency for a larger proportion of the feed to be collected at slower flow rates. Modelling on the basis of the observed flow profiles in conjunction with a theoretical fat concentration profile showed that the observed 'disproportionality' would have over-estimated fat intake by a mean of 2.6% per feed (S.D.9.1 range -18.9% to + 16.9%). Using the shield in random sequence at two out of the first four feeds after 0800 h, showed that an infant's mean milk intake with the shield was on average 32% less than on control feeds. Allowing for possible compensation by the infant when control feeds followed low shield intakes, mean milk intakes with the shield were 17% smaller than without the shield.

Relationships between nursing patterns, supplementary food intake and breast-milk intake in a rural Thai population.

Relationships between nursing patterns, supplementary food intake and breast-milk intake were examined in a group of 52 Thai babies under 1 year of age. All data were collected over two consecutive days, 24 h/day. Total sucking time (min/day) and supplementary food intake (kcal/day) were significant predictors of breast-milk intake after allowing for the age of the baby: R-squared is 0.32 for sucking time and 0.39 for supplementary food intake. The two variables were themselves correlated (r is -0.47). The number of breastfeeds per day and their mean duration was determined for each case, counting each episode of attachment to the breast as a separate feed. Number and mean duration of breastfeeds were then evaluated as predictor variables. The duration of feeds had no predictive power. Number of feeds was linearly related to milk intake and combined with age was as good a predictor of milk intake as total sucking time (with R-squared 0.34). These results suggest that a simple count of breastfeeds is as valuable as more complex measures of sucking duration in predicting to breast-milk intake.