J Richard Hamilton

Jaundice associated with severe bacterial infection in young infants.

The study is based on observations made on 24 young infants who developed jaundice in the course of a proved bacterial infection. Enteric bacilli, E. coli in particular, were the most frequently encountered etiological agents. Urinary infection occurred commonly. The sudden onset of jaundice and an elevated white blood count should make one suspicious of an infection. Bacterial cultures will establish the diagnosis. Treatment with an appropriate antibiotic results in rapid improvement of the jaundice. The theory is advanced that a hemolytic process leading to anemia and a retention type of jaundice is present initially. This is followed by toxic liver damage resulting in a regurgitation type of jaundice in most of these patients.

Impaired assimilation of nasojejunal feeds in healthy low-birth-weight newborn infants

We compared nasojejunal with nasogastric tube feeding in 18 healthy low-birth-weight infants from eight to 15 days of age. NJ-fed infants had significantly more stools and excreted significantly more fat and potassium in their stools. Growth and weight gain did not differ between the groups during the study period. Future use of NJ feeding in LBW infants should take into account the possibility of malabsorption associated with this technique.

Supplemental intravenous alimentation in low-birth-weight infants

Comparative effects of intravenously administered 10 per cent dextrose solution with and without the addition of 3.5 per cent fibrin hydrolysate were evaluated in the supplemental alimentation of gastric-fed, low-birth-weight infants (

Effect of Chronic Malnutrition on Intestinal Structure, Epithelial Renewal, and Enzymes in Suckling Rats

Summary: To evaluate the impact of malnutrition on the developing gut, we studied small bowel structure, epithelial renewal, and enzymes in suckling rats deprived of adequate nutrient from birth. Rat pups were suckled by foster dams fed ad libitum one of three isocaloric, semipurified diets containing 6,9, or 25% (control) protein throughout gestation and lactation. An additional control group consisted of pups raised with their natural, chow-fed mothers. Although survival of the pups, 98% in the chow-fed and 25% protein groups, decreased to 83% in the 9% groups and 53% in the 6% protein groups, body and gut weights were remarkably uniform within each study group. Mean body weight, gut weight, villus height, and crypt depth were markedly and significantly less in the 6 and 9% pups when compared with those in the chow and 25% control groups, the 6% group being significantly more affected was than the 9% group (P < 0.001). Pups raised by chow-fed mothers also weighed significantly less (P < 0.001) than did those raised by dams fed the 25% protein diet. Total small intestinal protein and DNA content of mucosal scrapings were less in 6 than 9% rat pups (P < 0.001), which in turn were less than those in the 25% group (P < 0.05). The protein/DNA ratio in the small intestine of the 6% animals only was reduced when compared with the 25% group (P < 0.05). Epithelial cell migration assessed by autoradiography with [3H]thymidine was significantly slower in both proximal and distal intestinal segments of the 6% animals when compared with those from the 25% group (P < 0.001). Incorporation of the 3H, seen by autoradiography after 1 hr, was also signficantly decreased in the 6% group (P < 0.001). Calculated for the total small intestine, lactase, sucrase, alkaline phosphatase, and thymidine kinase activities were significantly diminished (P ≤ 0.001) in the 6% animals compared with 25% controls. Calculated in relation to mucosal protein content and compared with 25% controls, sucrase and alkaline phosphatase activities were significantly decreased (P < 0.001) in both proximal and distal small intestinal segments of the 6% animals, but thymidine kinase activity was decreased only in the distal segment (P < 0.001). However, lactase specific activity was increased in both proximal and distal segments from the 6% group (P < 0.001). Further studies of this phenomenon demonstrated a significant increase in intracellular acid β-galac-tosidase (P < 0.001), particularly in the distal intestinal segment, but also a marked increase in brush border β-galactosidase.Our data demonstrate that in the small intestinal mucosa of the suckling rat, chronic malnutrition causes a decreased number of cells and impaired epithelial proliferation. These abnormalities reflect a profound direct impact of malnutrition on the gut of the young animal and demonstrate a delay in the normal pattern of postnatal maturation of the small intestinal epithelium.

Childhood celiac disease: Response of treated patients to a small uniform daily dose of wheat gluten

We undertook a detailed reassessment of 23 children with proved celiac disease 3.8 ±1.0 years after initiation of dietary therapy. Thirteen had normal duodenal biopsies; ten biopsies were typical of active celiac disease. Each received a constant dose of wheat gluten for six days in the hospital; one developed symptoms. Duodenal biopsy, repeated in the 13 with normal structure before gluten, was normal in all but one patient after six days. Of those 12 patients with normal mucosa after six days, three developed symptoms after one to six months of ingesting gluten. The three symptomatic patients and the nine asymptomatic patients assessed after 12 to 15 months developed both mucosal lesions typical of celiac disease and decreased mucosal disaccharidase activities. Fat excretion and linear growth were not affected, but weight gain was affected by the gluten challenge. In a large group of unselected proved cases of celiac disease, we found none with transient gluten intolerance. We advocate long-term dietary therapy for all cases diagnosed in childhood.

Alanine Enhances Jejunal Sodium Absorption in the Presence of Glucose Studies in Piglet Viral Diarrhea

ABSTRACT. We measured the response of jejunal sodium (Na) absorption to neutral amino acid (L-alanine) and to dipeptides (L-alanyl-L-alanine, glycylsarcosine) in normal piglets and in piglets with acute viral diarrhea after experimental infection with transmissible gastroenteritis (TGE) virus. In the TGE jejunum villi were blunted, crypts were deepened, and the epithelium was composed of relatively undifferentiated cells with reduced disaccharidase, decreased sodium-potassium-stimulated ATPase, and elevated thymidine kinase activities. The response of Na absorption to a maximal concentration of L-alanine (20 mM) or D-glucose (30 mM) was significantly blunted in TGE jejunum in Ussing chambers. However, the addition of L-alanine together with D-glucose caused a significantly greater increment of Na absorption than either L-alanine or D-glucose alone in control and TGE tissue. The effect of Na absorption of the dipeptide L-alanyl-L-alanine (10 mM), which was rapidly hydrolyzed by control and TGE mucosa, was similar to that of L-alanine (20 mM), while glycylsarcosine, a poorly hydrolyzed dipeptide, did not change net Na absorption in the jejunum. Our data support the concept of separate carrier systems for neutral amino acid and hexose in the crypt-type intestinal epithelium characterizing viral enteritis. We speculate that a sodium-cotransporting amino acid, if added to oral glucose-electrolyte solutions, could benefit oral rehydration therapy in acute viral diarrhea; neither of the dipeptides tested here can be expected to enhance absorption to any greater extent than its constituent amino acids.

Impact of Chronic Protein-Calorie Malnutrition on Small Intestinal Repair after Acute Viral Enteritis: A Study in Gnotobiotic Piglets

ABSTRACT: To investigate the effect of chronic proteincalorie malnutrition on intestinal repair after an enteric infection, we examined small intestinal structure, enzyme activity, and sodium transport in undernourished piglets during the acute and convalescent phases of a viral enteritis, transmissible gastroenteritis (TGE). Gnotobiotic pigs, nutritionally deprived from the age of 7 days, gained less weight than dietary controls from 14 days of age until the end of the study. Animals from malnourished and control diet groups were innoculated with TGE virus at 22-23 days and studied during the acute (40 h) and convalescent (4, 10, and 15 days) stages of this experimental enteritis along with noninfected dietary controls. After TGE infection, we observed a further decrease in weight gain and an increased mortality only in undernourished pigs. In jejunum and ileum of both dietary groups at 40 h after TGE infection, we observed comparable structural lesions, similar decreased activities of mucosal enzymes (sucrase, lactase, sodium-potassium-dependent ATPase), and increased thymidine kinase activities. Also we noted comparable diminution of glucose-stimulated jejunal sodium absorption in both dietary groups at 40 h. In control diet pigs, transport abnormalities recovered by 4 days after TGE infection and normal mucosal structure and enzyme activity returned over 4-15 days. In undernourished piglets, structural repair and enzyme abnormalities were prolonged when compared with the control diet group; glucose-stimulated sodium transport did not recover until 10 days after infection and never regained the enhanced activity seen in noninfected undernourished controls. We conclude that small intestinal recovery of the undernourished animal after viral enteritis is prolonged and speculate that impaired mucosal repair is important determinant of the delayed recovery of structural and functional abnormalities in this animal model of a major human disease.

Sodium ion transport in isolated intestinal epithelial cells. The effect of actively transported sugars on sodium ion efflux

Abstract A technique to measure Na+ efflux from isolated intestinal epithelial cells has permitted us to examine the mechanisms responsible for Na+ transport in absorptive cells without contamination by other cell types. We examined the effect of actively transported sugars on Na+ efflux from isolated rat jejunal epithelial cells to evaluate the mechanism by which actively transported non-electrolytes stimulate Na+ absorption. Glucose, galactose and 3-O- methylglucose , sugars known to be actively transported by the small intestine, stimulate total Na+ efflux from isolated epithelial cells. This stimulation results from an increase of active Na+ transport, since it is inhibited by ouabain. Glucose stimulation is significantly greater than that produced by galactose or 3-O- methylglucose , 2-Deoxyglucose, a sugar that is not actively transported, has no effect on total Na+ efflux from isolated cells. Phloridzin, which has no effect on Na+ efflux in a sugar-free medium, completely abolishes the effect of galactose. These findings (a) support the hypothesis that the increase in intestinal absorption of Na+ in the presence of actively transported non-electrolytes occurs by a transcellular route; and (b) are consistent with the ion-gradient model. The results are not compatible with the direct energy-coupling model.

Recent Developments in Viral Gastroenteritis

In recent years impressive advances have been made in understanding viral gastroenteritis. A specific causative agent has been identified in infants and young children, and studies of a similar but distinct enteritis in piglets have given new insight into the pathogenesis of viral diarrhea. This article discusses these recent findings in veterinary and human medicine.

Effect of glucocorticoid on piglet jejunal mucosa during acute viral enteritis.

ABSTRACT: We measured the effect of pharmacological doses of glucocorticoid on piglet jejunal structure and function during acute viral diarrhea. Weaned piglets, infected experimentally with transmissible gastroenteritis virus, a coronavirus that induces a diarrheal illness similar to human rotavirus infection, received methylprednisolone (30 mg/kg) or saline intramuscularly at 48 and 72 h after infection; noninfected littermate controls were similarly injected with methylprednisolone. Animals were killed at 96 h, at the height of diarrhea, and jejunal epithelium was studied in vitro. Transmissible gastroenteritis, as expected, induced structural, enzyme, and Na transport abnormalities. Methylprednisolone did not affect small intestinal structure or function of noninfected control piglets. In transmissible gastroenteritis-infected piglets, jejunal villi were longer and glucose-facilitated Na absorption was greater after methylprednisolone than after saline treatment. Increased glucose stimulation of Na flux in vitro in the methylprednisolone-treated infected group was not attributable to enhanced Na+-K+-ATPase activity and occurred despite persistence of the virus within mucosal cells, shown by immunofluorescense microscopy. In this piglet model of viral diarrhea, early regeneration of absorptive surface that precedes recovery of disaccharidase function is accelerated by glucocorticoid therapy.ABSTRACT: We measured the effect of pharmacological doses of glucocorticoid on piglet jejunal structure and function during acute viral diarrhea. Weaned piglets, infected experimentally with transmissible gastroenteritis virus, a coronavirus that induces a diarrheal illness similar to human rotavirus infection, received methylprednisolone (30 mg/kg) or saline intramuscularly at 48 and 72 h after infection; noninfected littermate controls were similarly injected with methylprednisolone. Animals were killed at 96 h, at the height of diarrhea, and jejunal epithelium was studied in vitro. Transmissible gastroenteritis, as expected, induced structural, enzyme, and Na transport abnormalities. Methylprednisolone did not affect small intestinal structure or function of noninfected control piglets. In transmissible gastroenteritis-infected piglets, jejunal villi were longer and glucose-facilitated Na absorption was greater after methylprednisolone than after saline treatment. Increased glucose stimulation of Na flux in vitro in the methylprednisolone-treated infected group was not attributable to enhanced Na+-K+-ATPase activity and occurred despite persistence of the virus within mucosal cells, shown by immunofluorescense microscopy. In this piglet model of viral diarrhea, early regeneration of absorptive surface that precedes recovery of disaccharidase function is accelerated by glucocorticoid therapy.