Supplemental oxygen may decrease progression of prethreshold disease to threshold retinopathy of prematurity.

The optimum level of oxygen saturation for infants with prethreshold retinopathy of prematurity (ROP) is unknown. We reviewed our conversion rate from prethreshold to threshold ROP between 1985 and 1993 during which time target levels of oxygen saturation rose in a stepwise fashion. A retrospective study of 153 infants with prethreshold ROP was performed at Stanford University between 1985 and 1993 that showed that target minimum oxygen saturation rose from 92% (1985-1987) to 95% (1988) to 96% (1989) to 99% (1990-1993). In addition, we looked at 26 infants between 1994 and 1996 who were excluded from the STOP-ROP study and who were not receiving supplemental oxygen in an effort to maintain equipoise for that study. Infant characteristics were tabulated, and rates of progression from prethreshold to threshold ROP were calculated. Rates of progression to threshold varied little between 1985 and 1989 (average 37%), but dropped to 7% for the period between 1990 and 1993. From 1994 through 1996 the rate of progression to threshold disease rose again, to 38%. Moderate supplemental oxygen (target saturation 99% with PO2 no higher than 100 mm Hg) was associated with regression of prethreshold ROP, without appearing to arrest retinal vascular maturation.

Effects of microwave radiation on anti-infective factors in human milk.

In intensive care nurseries it has become common practice to use microwave thawing of frozen human milk for more rapid accessibility. Twenty-two freshly frozen human milk samples were tested for lysozyme activity, total IgA, and specific secretory IgA to Escherichia coli serotypes 01, 04, and 06. The samples were heated by microwave for 30 seconds at a low- or high-power setting and then reanalyzed. One-mL aliquots of 10 additional human milk samples were microwaved at low (20 degrees C to 25 degrees C), medium (60 degrees C to 70 degrees C), and high (greater than or equal to 98 degrees C) setting before the addition to each of 1 mL of diluted E coli suspension. E coli growth was determined after 3 1/2 hours of incubation at 37 degrees C. Microwaving at high temperatures (72 degrees C to 98 degrees C) caused a marked decrease in activity of all the tested antiinfective factors. E coli growth at greater than or equal to 98 degrees C was 18 times that of control human milk. Microwaving at low temperatures (20 degrees C to 53 degrees C) had no significant effect on total IgA, specific IgA to E coli serotypes 01 and 04, but did significantly decrease lysozyme and specific IgA to E coli serotype 06. Even at 20 degrees C to 25 degrees C, E coli growth was five times that of control human milk. Microwaving appears to be contraindicated at high temperatures, and questions regarding its safety exist even at low temperatures.

Mechanism of maturational decline of rat intestinal lactase-phlorizin hydrolase.

The maturational decline in lactase-phlorizin hydrolase (LPH) activity was studied in groups of young rats ranging from suckling to early post-weaned states. Associated maturational increases in sucrase-isomaltase (SI) and maltase-glucoamylase (MG) activities were also examined as a comparison. Over this time period changes in cellular concentrations of the three enzymes were observed, reflecting corresponding changes in enzyme activities. Synthesis patterns accompanying these maturational changes in concentration were examined using labelled leucine as a marker. Synthesis of LPH was found to be maintained at constant rates independent of the maturation-associated decline in its concentration, whereas the increases in cellular concentrations of SI and MG were due to accelerated synthesis of the enzyme. Turnover of LPH, based on both the fractional synthesis rate and the disappearance rate of labelled leucine from prelabelled LPH pools, was increased in a quantitatively similar way to the decline in LPH concentration. These findings are consistent with our earlier proposal that the maturational decline of LPH occurs because of accelerated turnover, without a decrease in its rate of synthesis.

Dietary CHO and stimulation of carbohydrases along villus column of fasted rat jejunum.

Adult rats when fed a high carbohydrate diet of 70% sucrose or glucose for 24 h following a 4-day fast showed increased concentrations of intestinal sucrase-isomaltase (EC 3.2.1.48, EC 3.2.1.10) and maltase-glucoamylase (EC 3.2.1.20) but not lactase-phlorizin hydrolase (EC 3.2.1.23, EC 3.2.1.62). The concentration increases of these enzymes were accompanied by corresponding acceleration of their synthesis rates. Contrary to earlier studies by others, suggesting that upper villus cells in the fasted intestine are unresponsive to stimulation of sucrase activity by refeeding a high-sucrose diet, the concentration increases of both sucrase-isomaltase and maltase-glucoamylase were seen to occur in cells all along the length of the villus column. The earlier studies differed from the present study by basing enzyme assays relative to protein rather than the DNA content of villus cell fractions. We have shown that villus cells increase their protein content severalfold while migrating to villus tip, providing the basis for the difference between earlier and the present findings. Further evidence that stimulation of sucrase-isomaltase and maltase-glucoamylase by high carbohydrate is not restricted to the crypt and lower villus region was obtained by the finding that their synthesis rates appeared to be equally stimulated along the length of the villus column.

Maturational patterns of carbohydrases in the ileal remnant of rats after jejunectomy at infancy.

The enteric epithelium of suckling rat undergoes dramatic functional and cytokinetic changes (redifferentiation) with maturation. Ileal epithelial maturation was studied in infant rats subjected to 60% proximal enterectomy at age 10 d in an effort to examine redifferentiation mechanisms. Two months after resection the residual ileal remnant was increased in diameter, weight, total protein, and DNA per unit length compared with ileal segments from control littermates that had laparotomy without resection. The residual ileum demonstrated increased sucrase activity per unit length but was indistinguishable from control ileal segments in activity per unit DNA or villus distribution. Lactase activity was negligible in all segments of the residual intestine. Villus height and crypt depth were increased in the residual ileum with slight increases in cell turnover and cell-migration rates. These results show the presence of an intrinsic program for regulation of ileal epithelial maturation and its resistance to alteration by a major stimulus applied before its expression.

Clinical uses, collection, and banking of human milk.

The Mothers' Milk Bank (MMB) of San Jose, CA, has provided banked human milk to clinicians and researchers since its founding in 1974. This article briefly acknowledges the many and varied reasons for the use of human milk. Its primary focus however, is to review the protocol followed by the MMB for collection, banking, and distribution of human milk.

Growth and differentiative maturation of the rat enterocyte.

Cells of the intestinal mucosa of the infant and adult rat maintain a pattern of continuous growth, accumulating structural and functional proteins and lipids while migrating the length of the villus column. Cells of jejunal and ileal segments were fractionated sequentially from villus tip to inner crypt and distribution patterns were determined for DNA, total protein, cholesterol, phospholipid, and disaccharidases. Patterns of increasing ratios of protein, lipids, and disaccharidases to DNA were maintained to villus tips, with only slight fall-off of enzymes observed. Distribution profiles of disaccharidases, when computed relative to protein (as seen in previous reports), show distortion of the true cellular distribution pattern of these enzymes as determined by the DNA content of the fractions. Wide variation in cell protein concentrations was evident between jejunal and ileal segments in pre- and postweaned rats. Ileal cells of the suckling rat contained particularly high protein concentrations, which appeared to be largely transitory in nature and related to food intake. Cholesterol and phospholipids were found to be concentrated in the microvillus membrane and account for a significantly large fraction of the cellular content of these lipids.

Effects of hydrocortisone on carbohydrase concentrations, de novo synthesis and turnover patterns in immature rat intestine.

Hydrocortisone administration to infant rats enhanced cellobiase and maltase activities and induced precocious expression of sucrase and trehalase activities along the length of the small intestine. These activity changes reflected proportional concentration increases in the enzymes lactase (EC 3.2.1.23), maltase/glucoamylase (EC 3.2.1.20) and sucrase-isomaltase (EC 3.2.1.48/10). Administration of an equivalent tracer dose of [3H]leucine (by body weight) to control and hydrocortisone-treated infant rats resulted in greater accumulation of label in the carbohydrase pools of the treated rats, suggesting their increased de novo synthesis. The increased concentrations of lactase and maltase/glucoamylase induced by exogenous hydrocortisone were matched by the presence of corresponding greater amounts of label in their brush border pools. Accumulation of label in each of the lactase, maltase/glucoamylase and sucrase-isomaltase pools was generally similar in the hydrocortisone-treated rats, suggesting equivalent stimulation of their synthesis as a group by the humoral agent. The turnover rates of the carbohydrases as a group were found to be similar and did not appear to differ in control and hydrocortisone-treated rats. Total protein synthesis rates were slightly greater in the intestine of the hydrocortisone-treated group of rats.

Nature of elevated rat intestinal carbohydrase activities after high-carbohydrate diet feeding.

Adult rats that were maintained on a low-carbohydrate intake showed rapid increase in the activities of sucrase, maltase, and lactase along the length of the small intestine when they were fed a high-starch diet. In the present study, we have identified these activity increases, and showed that they reflect proportional accumulations in enzyme-protein of sucrase-isomaltase (EC 3.2.1.10, 3.2.1.48), maltase-glucoamylase (EC 3.2.1.20), and neutral lactase (EC 3.2.1.23). It was determined that each of these enzymes exists in adult rat intestine in single immunoreactive form and accounts as a group for all sucrase, cellobiase, and most maltase and lactase activities. Dietary change from low to high carbohydrate (starch) resulted in an increase in [3H]leucine accumulation in each of the enzymes, without a change in the amount of label accumulation in total intestinal proteins. The increase in label accumulation in the brush-border carbohydrase pools was matched generally by proportional elevation in the pool concentrations of sucrase-isomaltase and lactase but not maltase. These studies suggest that the elevation of intestinal carbohydrase concentrations induced by high-carbohydrate feeding may involve selective stimulation of their synthesis.

The nature of maturational decline of intestinal lactase activity.

We have examined the nature of the decline of lactase (EC 3.2.1.23) activity in the maturing rat intestine. It was established in an initial study that the activity decline reflected a proportional reduction in the concentration of the enzyme protein. Accumulation patterns of label into lactase, total intestinal proteins and sucrase (EC 3.2.1.48)-isomaltase (EC 3.2.1.10) were compared, 4 h following administration of a tracer dose of [3H]leucine to weanling rats exhibiting a wide range of lactase decline. Accumulation of increasing amounts of label in total intestinal proteins and sucrase-isomaltase pools was found to accompany the lactase decline, in contrast to accumulation of a constant amount of label in the declining lactase pools. The pattern of increased label accumulation in total intestinal proteins was shown in a corollary study to reflect a corresponding acceleration of total protein synthesis. On this basis, the finding of a constant amount of label in the declining lactase pools suggested a constant synthesis of lactase. We proposed earlier that associated reductions in enterocyte life-span (leading to correspondingly less lactase accumulation) rather than suppressed synthesis may provide the primary causal basis of lactase decline in the postweaned mammal.

The natural history of subependymal germinal matrix hemorrhage.

A prospective study of 377 premature infants (less than or equal to 1500 gm) was undertaken to delineate the natural history of subependymal/intraventricular hemorrhage (S/IVH) and its complications using ultrasound (US) and computed tomography (CT). Low grade (I, II) S/IVH had a low mortality while higher grades (III, IV) still had elevated mortality rates. The addition of intraparenchymal hemorrhage (IPH) to S/IVH incrementally increased the incidence of death and other complications, suggesting IPH hemorrhage should be categorized separately. When a specific day could be identified, S/IVH had its onset in the first 7 days of life with peak incidence occurring on day 3. S/IVH appeared to be an event limited to less than 24 hours in all but 5% of infants in whom progression of hemorrhage was documented over a 24-hour period. The mortality rate of these progressive hemorrhages was high, 50%. The benign phenomenon of late S/IVH was detected in 5% of infants. These hemorrhages were clinically silent and of minor severity. Several complications of S/IVH were detected. Hydrocephalus was a significant complication only for higher grades of S/IVH. When present, severe hydrocephalus had an early onset and reached a maximum at around 3 weeks of age. "Atrophic change" of a cerebral hemisphere was detected in 30% of all S/IVH infants, while this was not seen in nonS/IVH infants. This "atrophic" abnormality had a marked predilection for the left hemisphere, independent of the site of the S/IVH. Periventricular leukomalacia (PVL) was documented by US in 2% of infants and could be detected in the first week of life. PVL presented in the first week of life as an echogenic lesion which developed "cystic" changes at approximately 3-4 weeks of age. This complication should be categorized separately from S/IVH.

Use of sodium nitroprusside in neonates: efficacy and safety.

Sodium nitroprusside was administered to 58 neonates, including 11 with severe respiratory distress syndrome, 15 with persistent pulmonary hypertension of the newborn, 28 with clinical shock, three with systemic hypertension, and two with pulmonary hypoplasia, all refractory to conventional intensive therapy. Nitroprusside was infused at 0.2 to 6.0 micrograms/kg/min for periods of 10 minutes to 126 hours. Infants with severe respiratory distress syndrome had increased PaO2 and decreased PaCO2 or peak inspiratory pressure, and nearly all (82%) survived. Infants with persistent pulmonary hypertension of the newborn had variable responses; improvement did not correlate with survival, but survival (47%) was identical to that in an earlier series of infants given tolazoline. Infants in shock had improved perfusion, urine output, and serum bicarbonate levels, and these responses were significantly related to survival. Hypertension was controlled in all three hypertensive infants. Adverse effects were very uncommon. Toxic effects were not observed. Sodium nitroprusside is effective and can be used safely in circulatory disorders in the neonate.

The bacterial content of breast milk after the early initiation of expression using a standard technique.

This study was initiated to evaluate the effect of early expression on the bacterial colony count of human milk. Significant bacterial contamination (greater than or equal to 10,000 colony-forming units/ml milk) was more common in 11 mothers who delayed the onset of expression of their milk compared with mothers who began to express their milk in the immediate postpartum period (n = 15) or who began to nurse their own full-term infants soon after delivery (n = 9). These data suggest that mothers who are separated from their prematurely born or sick infants should begin to express milk for their own infants as soon after birth as possible to provide milk with low bacterial contamination for frozen storage and later use.

Predicting survival among ventilator-dependent very low birth weight infants.

Ventilator-bound very low birth weight (VLBW) infants represent an increasing proportion of our nursery population. We reviewed the hospital course of 38 VLBW infants who required more than 1 month of intermittent mandatory ventilation (IMV) between 1976 and 1978. Twenty-eight infants survived; 10 died. There were no significant differences between survivors and nonsurvivors in estimated gestational age (EGA), Apgar scores, first pH, first mean arterial pressure (MAP), h of IMV required, or birth weight; nor did the incidence of patent ductus arteriosus (PDA), respiratory distress syndrome (RDS), or transport differ. Pneumothorax was significantly more common among those infants who died. When ventilator settings were reviewed, significant differences were found consistently between the 2 groups of 3, 5, and 7 days of age, but not at 1, 14, 21, or 28 days of age. A predictive model for estimating the probability of survival of such infants was developed based upon these data, employing birth weight, mean airway pressure (MAWP) at 7 days of age, and occurrence of pneumothorax, and was applied prospectively to a group of 29 such infants born in 1979 and 1980. Prediction of outcome was significantly more accurate than chance alone. We conclude that prolonged ventilator dependence is largely confined to VLBW infants; that it is the rule among infants less than 750 g; and that accurate, objective assessment of an individual infant's prognosis may lead to improved care.

Reactions of women to intrapartum fetal monitoring.

The present study examined the reactions of women to routine intrapartum fetal monitoring at a medical center and at a community hospital. Positive responses were found in an interview and on a questionnaire developed from interviews reported in prior studies. Women believed they understood the purpose of the monitor and used it for various purposes in labor. Some differences in reactions to intrapartum fetal monitoring were found to be based on particular characteristics of the women in each setting.