John N. Udall

Development of Gastrointestinal Mucosal Barrier. I. The Effect of Age on Intestinal Permeability to Macromolecules

Summary: Indirect evidence has suggested that increased quantities of antigen may penetrate the intestinal mucosa and enter the systemic circulation during the newborn period compared to adult life. However, no direct measurement of macromolecular transport has been reported as a function of perinatal age. To study this process, we administered 100 mg of tritiated bovine serum albumin ([3H]BSA) by gavage to rabbits at birth, one wk, 2 wk, 6 wk, and one year of age and measured plasma radioactivity 4 hr after gavage. Plasma concentration of trichloroacetic acid insoluble radioactivity and immunoreactive bovine serum albumin radioactivity decreased significantly after one wk of age. When adult animals were gavaged with the same amount of [3H]BSA per body weight as the one-wk-old animals, they failed to transport as much of the antigen as the younger animals. This study, therefore, provides objective evidence that the intestinal mucosal barrier of newborns may be incompletely developed at birth and allow increased intestinal transport of antigens into the circulation.Speculation: The development of an animal model for the study of gastrointestinal host defense during the neonatal period may ultimately provide the basis for a better understanding of the mechanisms responsible for intestinal uptake of antigenic molecules and their contribution, if any, to the pathogenesis of human disease. Of particular importance is the accurate quantitation of immunologically reactive antigen absorbed by newborn animals. Using immunologic techniques to quantitate macromolecular transport, it can be determined whether conditions (enteric delivery of nutrients, growth factors in natural milk, etc.) thought to stimulate intestinal epithelial cell turnover can also accelerate the development of the intestinal mucosal barrier and thereby contribute to the protection of the infant from potentially harmful luminal antigens.

Assessment of lactose absorption by measurement of urinary galactose

Individuals with sufficient intestinal lactase hydrolyze ingested lactose to galactose and glucose and these monosaccharides are absorbed. Lactose is not digested completely when intestinal lactase activity is low and the disaccharide is malabsorbed. Breath hydrogen excretion after lactose ingestion is used commonly to diagnose lactose malabsorption. However, no direct tests are currently used to assess lactose absorption. We tested a new method of assessing lactose absorption in 26 healthy individuals. Each subject ingested 50 g of lactose. Participants were evaluated for lactose malabsorption using a standard 3-h breath hydrogen test. In addition, the urinary excretions of galactose, lactose, and creatinine were quantitated for 3-5 h after lactose ingestion. On the basis of breath hydrogen analysis after lactose ingestion, 12 individuals were lactose malabsorbers (defined as a rise in the breath hydrogen concentration of greater than 20 parts per million above the baseline value). The 14 subjects who did not malabsorb lactose by breath hydrogen testing (defined as a rise in the breath hydrogen concentration of less than or equal to 20 parts per million above the baseline value), had significantly more galactose in their urine 1, 2, and 3 h after lactose ingestion than lactose malabsorbers. The ratio of excreted lactose to excreted galactose was significantly decreased in lactose absorbers compared with lactose malabsorbers (p less than 0.001). Determination of the ratio of urinary galactose to urinary creatinine separated lactose absorbers from lactose malabsorbers completely (p less than 0.001). We conclude from this study that the determination of urinary galactose, urinary lactose/galactose ratio, and urinary galactose/creatinine ratio may be used to assess lactose digestion and absorption in healthy adults.

Maternal obesity, weight gain in pregnancy, and infant birth weight☆

with streptococcus, staphylococcus, and E. roli. Ultimately, the diagnosis is made when the bacteria is cultured from either the throat, ceyvix, vagjna, urine, stool, or blood. Treatment should be started promptly because cure is dependent on it. Otherwise, transplacental spread of infection will lead to spontaneous abortion, intrauterine death, piemature labor and delivery, or neonatal sepsis and death, as in this case, secondary to complications of prematurity, i.e., respiratory distress syndrome and intraventricular hemorrhage. The drug of choice for Listeria is a penicillin, specifically ampicillin, or tetracycline; these antibiotics often empirically used. After appropriate treatment, repeat cultures should be taken to assure cure. If undiagnosed and not treated, maternal infection can lead to fetal infection via transplacental or direct-contact modes of spread. In summary, Listeria monocytogenes is a significant cause of spontaneous abortion, intrauterine death, premature labor, and neonatal sepsis. When suspected, it is easily treated with penicillin. The key to cure is prompt diagnosis and treatment. Failure to do so leads to serious sequelae and results in the additional trealment of an infected premature infant.

The effect of short-term starvation on mucosal barrier function in the newborn rabbit.

ABSTRACT: The compromised human newborn frequently presents with overwhelming feeding problems which lead to inadequate intake. These problems may affect the development of the small intestine, especially mucosal barrier function, leading to increased infections and susceptibility to allergens. To study this, an animal model was established using neonatal rabbits deprived of nutrients from birth until 72 h. Mucosal barrier function was compared in deprived and control (naturally fed 72-h-old animals) rabbits by measuring immunoreactive bovine serum albumin in serum 4 h after intragastric infusion of crystalline bovine serum albumin (200 mg/100 g body weight). Trypsin activity was measured in rinse fluid obtained from the small intestine. Representative sections of jejunum from control and experimental animals were formalin fixed and stained with hematoxylin and eosin for morphologic comparison. Following the bovine serum albumin feeding, a significantly increased serum immunoreactive bovine serum albumin and significantly decreased trypsin-like activity of the small intestinal rinse fluid was noted in starved animals compared to controls. In addition, the enterocytes of malnourished animals were more cuboidal and contained fewer and smaller supranuclear granules on microscopic examination than the enterocytes of controls. This study suggests that short-term starvation in newborns affects mucosal barrier function. Acute starvation may place newborns at increased risk for infections and allergic disease.

Nutritional support for pediatric patients with inflammatory bowel disease

Pediatric patients with ulcerative colitis and Crohns disease often suffer from malnutrition and growth failure. This is particularly true in pubertal children. Chronic insufficient nutrient intake is most often the cause of growth failure. Both parenteral nutrition and defined enteral formulas are available to rehabilitate patients with malnutrition and growth failure. Assessment of nutritional status and growth and the use of parenteral nutrition and defined enteral formulas to reverse malnutrition, growth failure, and inflammation in pediatric patients with inflammatory bowel disease are discussed.

Improved Lactation with Metoclopramide A Case Report

feed, it is a process which results from a complex interaction of hormones. These hormones induce significant morphologic changes in the breast during pregnancy, initiate the secretion of milk, and maintain milk production.2,3 Prolactin appears to be the most important hormone involved in the onset and maintenance of lactation; however, other hormones, including estrogen and progesterone, are involved. Lactogenesis increases significantly in the postpartum period, when estrogen and progesterone levels decrease. The tactile stimulus to maternal nipples by the suckling infant prompts afferent impulses to effect the release of prolactin from the pituitary, which stimulates milk flow. Continued milk production requires a delicate interplay of prolactin and other hormones. Lactation may falter for a variety of reasons, including weak sucking on the part of the infant and maternal stress, infection, or fatigue.4 Metoclopramide has been used recently when lactation falters. It stimulates prolactin secretion and thereby enhances milk productjon _3>5+ The purpose of this report is

Calcified thrombus in the right atrium: A rare complication of long-term parenteral nutrition in a child

A 5-year-old boy with short-bowel syndrome who receives home parenteral nutrition developed a calcified thrombus that involved the inferior vena cava (IVC) and the right atrium. Symptoms included 3 to 4 months of intermittent fever and 2 months of vague chest pain. Blood could not be aspirated from the IVC catheter and an IVC contrast study demonstrated the calcified thrombus. The intracardiac portion of the mass was removed surgically, but the IVC mass could not be completely excised. The boy developed a pericardial effusion 6 weeks after surgery. He was treated for this and 6 months after the initial surgery the patient was asymptomatic.

Intestinal Permeability to Intact Lactose in Newborns and Adults

Small amounts of lactose have been shown to be absorbed intact across the intestine and excreted unchanged in the urine of newborns and adults. We designed a study to quantitate the intestinal uptake and urinary excretion of this disaccharide in these age groups. Similar amounts of lactose were given orally to 17 term newborns (age: 24.8 +/- 3.0 h) as a standard infant formula, and to 15 adult lactose absorbers (age: 28.1 +/- 2.6 years) and 11 adult lactose malabsorbers (age: 24.7 +/- 2.9 years) as a 20% water solution. Following lactose ingestion, breath was collected every 30 or 60 min for 3 h and analyzed for hydrogen concentration. Urine was also collected, and lactose and creatinine concentrations were determined. Peak hydrogen concentration was less than 20 ppm above baseline in newborns and adult lactose absorbers and 85 +/- 14 ppm in adult lactose malabsorbers. Urinary lactose excretion, expressed as a function of body weight (mg/ml/kg b.w.), was substantially greater in newborns (4.2 +/- 0.82) than in adult lactose absorbers (0.29 +/- 0.07; p less than 0.001) and adult lactose malabsorbers (0.55 +/- 0.04; p less than 0.01). Similarly, urinary lactose excretion expressed as a ratio of urinary lactose to urinary creatinine (mg/mg) was increased (p less than 0.001) in newborns (2.05 +/- 0.26) when compared to adult lactose absorbers (0.11 +/- 0.02) and adult lactose malabsorbers (0.20 +/- 0.02). Our data demonstrate that the intestinal uptake and urinary excretion of intact lactose is significantly increased in newborns compared to adult subjects.

Passive transplacental immunization: influence on the detection of enteric antigen in the systemic circulation.

Summary: Female New Zealand white rabbits were immunized with bovine serum albumin (BSA). Litters which had never suckled, from immunized and nonimmunized rabbits, were tested at 4 h, 24 h, and 48 h after birth. After obtaining an initial blood sample, all infant rabbits were gavaged with 100 mg of BSA plus tracer amounts of [125I]-BSA. Infant rabbits born to immunized mothers had circulating antibody before feeding and pups from nonimmunized mothers had no detectable antibody to BSA. The fed animals were sacrificed at 3–4 h after gavage. Serum obtained from cardiac and portal blood was examined for protein bound radioactivity and for the presence of immunoreactive BSA (iBSA) by electroimmunodiffusion. All infant rabbits had radioactivity in their blood. Approximately 50% of the radioactivity in the serum of infant rabbits from nonimmunized does was protein bound and all of these animals had iBSA in portal or cardiac serum samples. Of the 33 infant rabbits from immunized does, only four had protein bound radioactivity in their serum. This radioactivity appeared to be associated with circulating immune complexes of [125I]-BSA-rabbit-anti-BSA antibodies. None of the 33 infant rabbits had iBSA detectable by electroimmunodiffusion.

652 INTESTINAL TRANSPORT AND LIVER UPTAKE OF A FOOD ADDTIVE PRESENT IN INFANT FORMULAS

Undegraded carrageenan, a sulfated polygalactan macromolecule, is used as an emulsifier in ready-to-use infant formulas. Although undegraded carrageenan has not been shown to be transported across the intestine the safety of this food additive has recently been questioned because of its toxic effect on the intestine and liver of laboratory animals (Lancet 1:602, 1980). We have shown that intestinal macromolecular transport is increased early in life, therefore, newborns may be more susceptible to any toxic effect of carrageenan. To investigate the intestinal transport and toxicity of carrageenan in newborn animals, 40 mgm of carrageenan, a quantity present in 5 oz of formula, was given by gavage to newborn rabbits. Cardiac and portal blood were obtained four hours later. The stomach, small intestine and liver of animals were removed and homogenized. Double gel-diffusion with antiserum raised to λ-carrageenan was used to detect the presence of carrageenan in blood and tissue specimens. The results are expressed in animals positive for carrageenan/animals tested.This data suggests that undegraded carrageenan is transported across the intestine and is cleared by the liver. Morphologic studies of the developing intestine and liver are currently in progress to determine the degree of carrageenan toxicity.