Philip Sunshine

Abstract

Hypoxic-ischemic encephalopathy continues to be a major problem in perinatal medicine because of the high mortality rate and neurological and intellectual impairment in the surviving infants. In addition to the acute necrotic damage that occurs in the neurons initially, reperfusion injury and secondary neuronal damage continue for 6 to 72 hours after the initial insult. Secondary cellular energy failure, membrane breakdown, cellular influx of calcium ions, elaboration of cytokines, and oxidation of excitory amino acids all contribute to enhanced apoptosis of the neurons. Newer forms of therapy including the use of oxygen-free radical inhibitors and mild to moderate cerebral or systemic hypothermia for 72 hours following the asphyxial period are promising adjuncts as follow-up approaches to the affected newborns.

View details for PubMedID 12108076

View details for PubMedID 10685214

Abstract

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.

View details for PubMedID 9447528

View details for Web of Science ID A1996UP10300001

Abstract

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.

View details for Web of Science ID A1992HM25100018

View details for PubMedID 1557249

Abstract

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.

View details for Web of Science ID A1992HF96800015

View details for PubMedID 1540126

Abstract

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.

View details for Web of Science ID A1989R955100077

View details for PubMedID 2492155

Abstract

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.

View details for Web of Science ID A1988N242700015

View details for PubMedID 3129930

View details for PubMedID 3694523

Abstract

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.

View details for Web of Science ID A1987G133400010

View details for PubMedID 3829570

Abstract

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.

View details for Web of Science ID A1986F118400024

View details for PubMedID 3794917

Abstract

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.

View details for Web of Science ID A1986A979400008

View details for PubMedID 3085973

Abstract

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.

View details for Web of Science ID A1985AAH1500023

View details for PubMedID 3917495

Abstract

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.

View details for Web of Science ID A1985ASS1500028

View details for PubMedID 2413770

Abstract

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.

View details for Web of Science ID A1985AKH8600011

View details for PubMedID 3922428

Abstract

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.

View details for Web of Science ID A1984RW76000022

View details for PubMedID 6694039

Abstract

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.

View details for Web of Science ID A1983QH45800007

View details for PubMedID 6831887

Abstract

From 1961 to 1976, 229 infants with birth weights ranging from 751 to 1,000 gm were admitted to the Stanford University Hospital Intensive Care Nursery. The overall neonatal mortality for these infants was 63% (144/229), and there were ten late deaths. Before 1967, no infant in this group who required mechanical ventilation survived; thereafter, 30% (34/114) of the ventilated patients survived. Of the 75 long-term survivors 60 participated in a high-risk infant follow-up program; these included 23 infants who had received mechanical ventilation. The mean birth weight of these infants was 928 +/- 67 (SD) gm. Seventeen children (28%) had significant morbidity: seven (12%) with severe handicaps and ten (17%) with moderate handicaps. During this same period, seven infants weighing less than 750 gm at birth were also observed. The three infants who had not required ventilatory support thrived; the other four infants had required respirators and were significantly handicapped. More recently, neonatal mortality for infants with birth weights from 751 to 1,000 gm has improved: for 1977 to 1980, it was 28% (33/118). Furthermore, neonatal mortality for ventilated infants in this weight group was 27% (26/95). These data indicate an improved prognosis for very low-birth-weight infants, even with ventilatory support.

View details for Web of Science ID A1982NN58700022

View details for PubMedID 7079021

Abstract

Forty-eight infants, including 14 premature infants who were appropriate size for gestational age (AGA), 10 full-term AGA infants, 18 full-term infants who were large for gestational age (LGA), and six premature LGA infants of diabetic mothers (IDMs), had measurements of skinfold thickness (SFT) in the first 72 h of life. For the 24 LGA infants, there was a significant positive correlation between maternal glycohemoglobin (Hb AIc) in the post-partum period and SFT (r = 0.42, p less than 0.05). Our observations in this study support those of others, demonstrating that SFT increases with increasing gestational age. In addition, they support the hypothesis that, in diabetic pregnancies, or pregnancies associated with an elevated Hb AIc, a reflection of the time-integrated blood glucose level over the weeks preceding parturition, fetal hyperglycemia and hyperinsulinemia stimulate increased triglyceride synthesis in adipose cells and lead to an increase in fetal subcutaneous fat.

View details for Web of Science ID A1982PB96400012

View details for PubMedID 6193261

Abstract

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.

View details for Web of Science ID A1982NR43400006

View details for PubMedID 7078907

Abstract

Of 22 survivors of gastroschisis and omphalocele, most had poor weight gain. Although one-third of gastroschisis babies were small-for-gestational age at birth, no other predisposing factors for poor growth could be demonstrated. No child had intrinsic gastrointestinal or metabolic sequelae at 3 years of age, as demonstrated by radiographic studies, fecal fat excretion, or serum chemistry screen. One-third of those tested had IQs less than 90; five had abnormal electroencephalograms; one had impaired hearing. Intellectual impairment was related to length of hospitalization due to a variety of nongastrointestinal factors. Neither growth nor intellectual development was related to the type of lesion present, even when IQ is corrected for prematurity. Impairment of growth and intellectual outcome may be related to prematurity, small-for-gestation birth weight, and nongastrointestinal neonatal complications.

View details for Web of Science ID A1982PF95000017

View details for PubMedID 6224924

View details for Web of Science ID A1981MC14800043

View details for PubMedID 6796076

Abstract

Over a two year period, 52 infants were found to have clinical signs of patent ductus arteriosus (PDA). Twenty-seven responded to fluid restriction and furosemide; the remaining 25 infants entered the Indomethacin (IN) study protocol. Their mean (+/- SE) gestational age was 29.3 (+/- 0.6) weeks and birth weight was 1,142 (+/- 80) gm. Either a placebo or IN (0.25 mg/kg) orally was given for two doses, 24 hours apart; if no response occurred, the patient was crossed over to the opposite medication. Using Chi-square analysis, a significant response rate to IN was found. There were no significant differences in birth weights, gestational ages, or fluid intake between responders and nonresponders. However, both responders and nonresponders required a prolonged ventilator course, suggesting factors other than PDA causing prolonged ventilatory requirements in these babies.

View details for Web of Science ID A1981LQ63100009

View details for PubMedID 7346744

Abstract

The effect of oral gentamicin on lactase, the major disaccharidase of the neonatal intestine, was studied using the suckling Wistar rat as a model. The jejunal lactase-specific activity of asphyxiated animals given oral gentamicin at a dose of 20 mg/kg/day for two days was significantly decreased compared to that of nonasphyxiated animals given oral saline (P less than 0.01). Although the intestinal lactase-specific activity of nonasphyxiated animals given oral gentamicin at a dose of 20 mg/kg/day for two days was not significantly different from that of animals given oral saline, a high dose of oral gentamicin (160 mg/kg/day) was associated with decreased lactase-specific activity in both the jejunum and ileum. Intramuscular administration of gentamicin was not associated with decreased intestinal lactase-specific activity. More information is needed regarding the mechanism of the biochemical injury associated with the oral use of aminoglycosides and its clinical significance, if any, in the human infant. Until this is known, the potential for such injury should be of special concern where prophylaxis against necrotizing enterocolitis is being considered, particularly in view of the increased tendency for treated infants to become colonized with gram negative organisms resistant to the antibiotic being used.

View details for Web of Science ID A1981LQ63100005

View details for PubMedID 6810292

Abstract

Ontogenic development continues after birth in mammalian enteric epithelium as an adaptive mechanism to extrauterine life. In the rat, particularly significant developmental changes in enteric structure, function, and cytokinetic properties occur over a short critical period (usually between 16 and 20 days of age), preparatory to dietary change with weaning. Surgical bypass of ileal segments was performed on suckling rats of 12-14 days of age, and the effect on subsequent intestinal development was studied in both the bypassed and the shortened segment remaining in continuity. The bypassed segment, although achieving normal maturational patterns of active sucrase appearance and maltase accumulation, continued to maintain coincident immature patterns of high lactose activity and low cell turnover times. The intestine in continuity showed precocious appearance of active sucrase and accumulation along with maltase to greater than control levels, accompanied by a normal coincident decline in lactase activity and enterocyte life-span. Involvement of intraluminal influences on various parameters of enteric ontogenic development is thus indicated with the effects expressed by a delay in the excluded (bypassed) segment and by stimulation in the shortened segment in continuity. Data are presented in further support of the hypothesis that the life-span of the enterocyte serves postnatally as a primary determinant of enteric lactase levels.

View details for Web of Science ID A1981LP54900023

View details for PubMedID 7227778

Abstract

We have established a new transfusion program for an intensive care nursery which is based on crossmatching several infants to the same unit of type O Rh0(D) negative packed red blood cells, dividing the unit into quadpacks, and allowing multiple entry into each quadpack over a 24-hour period in the nursery. With this procedure, each donor unit can be used to provide multiple transfusions to four infants over a four-day period. Follow-up of transfusion recipients revealed that 20% had evidence of previous or ongoing CMB infection at 10 months of age, a prevalence comparable to that for transfused infants in other studies. We found no evidence for transmission of HB infection and a low risk of allosensitization to red cell and lymphocyte antigens.

View details for Web of Science ID A1980KQ18700025

View details for PubMedID 6253615

Abstract

Of 40 survivors of necrotizing enterocolitis 19 were completely normal children at the time of follow-up, one to three years later. Among the other 21 children, only six had moderate to severe neurologic impairment, representing 15% of all survivors. Despite the fact that intestinal injury is the main feature of the neonatal disease, only four children were symptomatic from gastrointestinal sequelae, and none of these suffered failure to thrive. Thus, 81% (17) of the children with late morbidity had problems unrelated to the gastrointestinal tract. The nongastrointestinal morbidity was associated with prematurity and the degree of perinatal stress.

View details for Web of Science ID A1980KU96100021

View details for PubMedID 7454483

Abstract

Lactase and maltase, the predominant sugar hydrolases associated with the intestinal brush bordermembrane of the suckling rat, were purified essentially free of the other to near homogeneity (lactase at specific activity 23, maltase at specific activity 58), and their specific physiocochemical properties determined. Antisera prepared to each showed by immunodiffusion a single common precipitin line with pure enzyme and solubilized proteins of the brush border membrane. Brush border membranes were purified 26--35-fold from infant rat intestine. Membranes prepared from 10-day-old rats contained 32% protein, 43% lipid and 25% carbohydrate with lactase and maltase estimated to comprise in excess of 10% and 2%, respectively, of the membrane protein. Immunotitration curves of lactase and maltase showed equivalent antibody binding by the membrane-bound and free enzyme forms. Furthermore, antibody binding to one enzyme did not affect the immunotitration curve or the extractability (by papain or Triton X-100) of the other membrane-bound enzyme. It was concluded that the lactase and maltase molecules are attached singly on the external membrane surface in a spatially independent manner with their antigenic sites as freely available to antibody binding as exhibited by their papain-solubilized counterparts.

View details for Web of Science ID A1979HA71500020

View details for PubMedID 110347

Abstract

Thirty-nine critically ill infants with pulmonary disease received tolazoline because of severe hypoxemia refractory to administration of 100% O2 and mechanical ventilation. Twenty-seven (69%) of the infants responded with an increase in PaO2 greater than or equal to 20 torr in the first umbilical arterial gas after completion of the initial ten-minute infusion (1 to 2 mg/kg) of the drug. A response was not correlated with survival. The overall survival was 46%, essentially unchanged from our previous report (44%). Infants with hyaline membrane disease had the poorest survival rate (33%). Complications associated with the use of tolazoline occurred in 82% of the infants. A hypotensive reaction, defined as a 25% decrease in mean arterial pressure from the pre-tolazoline level, occurred in 67% of the infants, and more commonly in the infants with RDS (87%). In 11 infants who did not respond to the initial dose of tolazoline, the dose was increased up to 10 mg/kg/hour; only one infant responded, and eight (73%) had a hypotensive reaction.

View details for Web of Science ID A1979HN82900024

View details for PubMedID 480041

View details for Web of Science ID A1979HR74500011

View details for PubMedID 120008

Abstract

The arrangement of the sugar hydrolases, sucrase-isomaltase, maltase, and lactase on the microvillus membrane of rat intestine was investigated by immunological technique. The enzymes were purified essentially free of each other to near homogeneity and antisera of high specificity were obtained against each. Microvillus membranes were prepared routinely in high purity from rat intestine and contained an average 61% protein, 20% lipid, and 19% carbohydrate, with the sugar hydrolases comprising an estimated 20--25% of the membrane protein. The immunoreactivity of membrane-bound sucrase-isomaltase, maltase, and lactase was investigated with antisera demostrating specific reactivity to each, when tested in the presence of other membrane extractives. The membrane-bound enzymes were found in each case to combine with antibody in amounts equivalent to that required to effect precipitation of comparable units of the free enzymes from solution. Preloading membrane vesicles with antibodies to any two of the enzymes did not affect either the immunoreactivity or extractability (by papain or Triton X-100) of the third. The antibody-binding studies indicated an arrangement of these enzymes independent of each other on the membrane surface, in a manner allowing each to maintain a high degree of molecular freedom.

View details for Web of Science ID A1979HS69800001

View details for PubMedID 116006

Abstract

The prevalence of primary adult lactose malabsorption and the pattern of milk use were studied among 109 Indians from various tribes of the American Great Basin and Southwest. Included were 100 persons who reported being full-blooded Indians as well as three with Mexican admixture and 6 with some European ancestry. Lactose malabsorption was found in 92% of the full-blooded Indians but in only 50% Indians who acknowledged European admixture. These results agree with those of studies of native Americans done elsewhere which show very high prevalences of such lactose malabsorption among adults reported as fullblooded and lower prevalences among individuals with admitted European ancestors. The suggestion made is that in pre-Colombian times, before interbreeding with Europeans began on any scale, such lactose malabsorption may have been nearly universal among native American adults. Most of the Indians studied consumed abundant milk since childhood but were nevertheless predominantly malabsorbers as adults. This argues against the induction hypothesis advanced by some to explain the striking ethnic differences that occur around the world in primary adult lactose malabsorption.

View details for Web of Science ID A1978ES37400002

View details for PubMedID 580162

Abstract

The effects of pasteurization, lyophilization, and freezing on immunoglobulin and lymphocytes in human milk was studied. We found a significant decrease in total lymphocyte count after all three processing methods. Pasteurization and lyophilization caused a significant decrease in immunoglobulin concentration and in specific antibody titer to Escherichi coli. Freezing specimens up to four weeks resulted in no significant alteration of IgA content or in E. coli antibody titer. Since a major advantage of human milk is the transference of passive local immunity, these quantitative changes may have clinical importance.

View details for Web of Science ID A1977EC66200008

View details for PubMedID 336859

Abstract

The intractable diarrhoea syndrome of infancy continues to be a major diagnostic and therapeutic challenge to the paediatrician and paediatric gastroenterologist. A carefully organized, staged approach to diagnosis will provide the best method of identifying those infants in whom a specific aetiology exists and for whom specific therapy is often available. Regardless of aetiology, however, the early use of appropriate nutritional support will not only reduce morbidity and mortality in these infants, but will prevent the development of many of the secondary consequences of malnutrition. The physician must compulsively pay attention to the details of daily management and provide an organized approach to diagnosis and treatment in order to improve the outcome of infants with intractable diarrhoea.

View details for Web of Science ID A1977DJ59400014

View details for PubMedID 195759

Abstract

Lactose loading tests and other means were used to determine the pattern of primary "adult" lactose malabsorption (LM) and milk use among 171 subjects, including 122 children and 49 adults, almost all of them Pima Indians of Arizona. LM develops at quite young ages in full-blooded Pima children: already in the 3- to 4-year age group, 40% had LM. Of 62 full-blooded Indians (greater than or equal to 4 years of age), 59 (95%) had LM. Of 41 Indians (greater than or equal to 4 years) who were of mixed Indian-northern European ancestry, however, only 25 (61%) had LM, and, among them, prevalence of LM correlated with degree of northern European admixture. Whereas only 21% of Pima lactose absorbers reported symptoms after the loading test, 72% of malabsorbers did so, with older malabsorbers more likely to experience symptoms. In their everyday lives, only 23% of malabsorbers recognized symptoms brought on by milk consumption, but the percentage of malabsorbers making such an association increased with age. Nevertheless the Pima, adults as well as children, continue to drink reasonable quantities of milk. Family pedigrees are consistent with the hypothesis that adult lactose absorption is inherited as an autosomal dominant trait. Over-all results of this study, moreover, support the geographic hypothesis advanced to explain ethnic or racial differences in prevalence of LM, rather than the induction hypothesis.

View details for Web of Science ID A1977EC57700006

View details for PubMedID 578795

View details for Web of Science ID A1976BD83000027

View details for PubMedID 1249697

Abstract

A prospective study was carried out to identify the immediate and long-range advantages and disadvantages of a walking-donor transfusion program for an intensive care newborn nursery. The effect of heparin on coagulation of blood was evaluated and found to be minimal. There was no evidence of transmission of HBSAg. The prevalence of CMV infection at the time of follow-up was higher in infants who had received blood from donors seropositive for CMV than in infants who had been transfused from seronegative donors. In our experience, a walking-donor program has been a safe and effective method for the provision of small transfusions of blood to sick neonates.

View details for Web of Science ID A1976CG39900030

View details for PubMedID 182947

Abstract

Forty-six neonates with hypoxemia were treated with tolazoline, a pulmonary vasodilator, within the first two days of life. Eight of ten (80%) infants without apparent lung disease responded with a mean increase in PaO2 of 116 torr within one hour of beginning tolazoline infusions. One of the responding infants and two nonresponders died. Thirty-six additional infants with a variety of pulmonary disorders had severe hypoxemia which was refractory to mechanical ventilation. Twenty-one (58%) responded with a mean increase in PaO2 of 130 torr within one hour after beginning tolazoline and 13 (62%) of these survived. Fifteen patients had little or no improvement in PaO2 following tolazoline and only three (20%) of these infants survived. Responders could not be distinguished from nonresponders by clinical or laboratory features prior to therapy with tolazoline. Fourteen infants experienced complications possibly related to tolazoline.

View details for Web of Science ID A1976CG39900023

View details for PubMedID 1085352

Abstract

The rates of colonization and infection of newborns with coagulase-positive staphylococci were studied during five sequential periods using various modes of skin care in the nursery. Colonization and infection were low during the baseline period when total body bathing with 3% hexachlorophene was employed (period 1), but increased dramatically (80% colonization, 9.5% infection) when hexachlorophene was discontinued and replaced by Ivory Soap baths (period 2). Reinstitution of hexachlorophene (period 3) reduced both colonization and infection, but not to the low levels seen during period 1. A second Ivory Soap period (period 4) resulted in a return to high colonization (77%) and infection (11.5%) rates. During period 5, daily Ivory Soap baths were continued and bacitracin ointment was applied to the umbilical area at least three times daily. Colonization was reduced to 10% and infection to 3.0%. Bacitracin could not be detected in serum in 15 infants studied. Colonization with gram-negative enteric bacilli was highest while using hexachlorophene or Ivory-bacitracin, but no increase in gram-negative infections was seen. Colonization of newborns with non-group A beta-hemolytic streptococci was not influenced predictably with various modes of skin care. The local application of bacitracin is a safe and effective method of controlling staphylococcal colonization and disease for infants in nurseries.

View details for Web of Science ID A1976CD09900011

View details for PubMedID 958762

Abstract

Urea cycle function was evaluated in liver obtained from six patients with Reye's syndrome and from five control subjects. Reye's syndrome patients demonstrated normal activities for the extramitochondrial portion of the urea cycle, but showed marked abnormalities of the mitochondrial enzymes, i.e., carbamyl phosphate synthetase (CPS) and ornithine transcarbamylase (OTC) (Tables 2,3). CPS activity was reduced to less than 15% of control values in all four patients from whom tissues was obtained during the first 72 hr after the onset of encephalopathy. Two patents from whom tissue was not obtained until after 9 days of symptoms showed no reduction in CPS activity. The OTC activity was also reduced (3-67% of control values) in the four patients from whom tissue was obtained early in the illness. In addition, greater than 60% reduction in Vmax and Km for carbamyl phosphate was noted in all four patients in whom sample size permitted kinetic analysis, including both patients in whom CPS and OTC activity were not markedly reduced. The same kinetic abnormality as well as decreased CPS activity were experimentally produced in normal rate liver incubated in the presence of 1.0 mM 4-pentenoic acid, a short chain fatty acid and known hepatic mitochondrial toxin (Table 4).

View details for Web of Science ID A1975AU05700005

View details for PubMedID 171618

View details for Web of Science ID A1974R846600002

View details for PubMedID 4809308

View details for Web of Science ID A1974R896200017

View details for PubMedID 4809413

View details for Web of Science ID A1974S041000027

View details for Web of Science ID A1974S456200010

View details for Web of Science ID A1973Q523800010