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Biomedical subjects

J R Hamilton

Publications and source records attributed to J R Hamilton.

At least 145 records · Page 8Linked to original sources
PubMed1980

The postnatal development of sodium transport in the proximal small intestine of the rabbit.

To investigate the postnatal development of intestinal Na+ transport, a major determinant of fluid absorption, we measured spontaneous and glucose-coupled Na+ transport across short-circuited epithelium and in isolated villus enterocytes from rabbit jejunum at age intervals after birth. Villus cells from suckling animals actively transported Na+ and responded to glucose, but their capacity to do so was less than that of villus cells from older animals. Net Na+ fluxes across short-circuited epithelium from suckling animals failed to respond to glucose, remaining negligible and less than adult values. This lack of response to glucose in tissue from younger animals was associated with marked paracellular shunting as evidenced by greater unidirectional fluxes and greater tissue conductance. Villus enterocytes from suckling animals compared to those from adults had reduced (Na+-K+)ATPase activity, but were rich in thymidine kinase. We conclude that proximal intestinal epithelium in suckling animals has a limited capacity for active Na+ transport, is incompletely differentiated, and is leaky, with a greater permeability for ions compared with adult intestine.

Age Factors↗
PubMed1979

A clinical study of young infants after small intestinal resection.

We prospectively studied 15 infants who, before 3 months of age, underwent resection of the small intestine-proximal in 3 infants, mid in 6, and distal in 6. Two died before one year of age. Many required prolonged parenteral nutrition, but by one year, 12 of the 13 survivors were on oral feedings only, and seven were above the third percentile for height and weight. Developmental delay occurred in the early postoperative period but diminished with time. There was compensatory adaptation of the remaining gut, shown by improving fat and B12 absorption and duodenal bile-salt concentrations. Bacterial contamination complicating end-to-side anastomoses occurred in two cases (P), gastric hyperacidity in four of 12 (1P, 3M), and hyperoxaluria in eight of 14 (1P, 5M, 2D). Studies of immune competence revealed normal cellular immune function (11/11), transient hypogammaglobulinemia (3/14), hypocomplementemia (1/12), and serum autoantibodies (3/10). Thus, massive resection of the small intestine did not preclude spontaneous improvement in absorptive function, growth, and development.

Child Development↗
PubMed1979

Evaluation of a detoxification service of habitual drunken offenders.

The progress of 52 chronic alcoholic habitual drunken offenders who were offered a detoxification, assessment and referral service as an alternative to penal management for their public drunkenness was compared over a year with 48 control subjects, and each group's progress in the experimental year was compared with that in the previous year. The 'detoxification' patients were found not to have benefited as regards their alcoholism or episodes of drunkenness, though their periods of abstinence were longer. There were significant improvements in their accommodation and self-reported quality of life, and it is likely that their physical and perhaps mental health improved.

Alcoholism↗
PubMed1979

Determinants of diarrhea in viral enteritis. The role of ion transport and epithelial changes in the ileum in transmissible gastroenteritis in piglets.

To understand mechanisms of viral diarrhea further, we studied ileal ion transport in vitro in relation to mucosal changes and epithelial differentiation in transmissible gastroenteritis in piglets, an invasive viral enteritis thought to involve mainly proximal intestine. In infected pigs, at the height of diarrhea, short-circuited ileal epithelium failed actively to transport Na+ and Cl-, and there was a defect of glucose-mediated Na+ transport. The Cl- secretory response to theophylline remained intact. Conductance measurements indicate that paracellular permeability may be reduced and transcellular transport may be altered. A mucosal lesion was observed at the time of the transport changes, characterized by villus blunting, crypt hyperplasia, and immature crypt-type enterocytes on the villus epithelium, deficient in disaccharidase and (Na+, K+)ATPase activity but rich in thymidine kinase. Consideration of the major determinants of diarrhea in this invasive enteritis must take into account not only altered mucosal function and differentiation but also the extent of intestinal involvement, including the ileum, a major site of fluid absorption in the intestine.

Animals↗
PubMed1978

Intestinal function in infants with severe congenital heart disease.

We evaluated digestive tract function in 21 young infants with severe congenital heart disease. One group had congestive heart failure and ventricular septal defect or single ventricle; the other had cyanosis and transposition of the great arteries. Enteric protein loss was excessive in eight patients, and steatorrhea was found in five. These abnormalities were mild and not related to the type or severity of the cardiac lesion. Available evidence points to a need of these babies for calories in excess of normal requirements for weight. The present study suggests that in designing dietary regimens for these very sick patients, their potential for defective gastrointestinal function must be considered. Because no consistent pattern of abnormalities in apparent, each patient who fails to thrive may deserve gastroenterologic evaluation.

Body Weight↗
PubMed1978

Synergistic infection with murine cytomegalovirus and Pseudomonas aeruginosa in mice.

A previous report from this laboratory demonstrated that mice infected intraperitoneally with a 0--20% lethal inoculum of murine cytomegalovirus (CMV) exhibited markedly enhanced mortality rates (90%--100%) within 48 hr after an intravenous injection of a 0--20% lethal inoculum of Pseudomonas aeruginosa. The current study demonstrated that mice infected with murine CMV alone had high titers of virus in multiple organs over a 20-day period, whereas mice injected with P. aeruginosa alone had a self-limited infection confined to the kidney. In the combined murine CMV-P. aeruginosa infection, titers of virus in tissues were changed very little. In contrast, P. aeruginosa was recovered in high concentrations from multiple organs, a finding which demonstrated a progressive systemic infection closely resembling that produced by a 100% lethal inoculum of P. aeruginosa alone in normal mice. An increased mortality rate due to P. aeruginosa in murine CMV-infected mice was dependent on inoculation of live bacteria and could not be explained by enhanced susceptibility to endotoxin. These results indicate that murine CMF markedly enhanced the suceptibility of mice to infection with P. aeruginosa and suggest that the virus altered mechanisms of host resistance important in recovery from bacterial infections.

Animals↗
PubMed1978

Familial enteropathy: a syndrome of protracted diarrhea from birth, failure to thrive, and hypoplastic villus atrophy.

We have studied 5 infants with persistent severe diarrhea from birth and marked abnormalities of absorption associated with failure to thrive leading to death in 4 infants. Three had siblings who died and a sibling of a 4th is ill at present, all with a similar illness; 2 were the products of consanguinous marriages. Exhaustive investigation failed to identify a recognized disease entity in any patient. Steatorrhea, sugar malabsorption, dehydration, and acidosis were severe in all patients, whatever the diet fed. Total parenteral nutrition was used, but excessive stool water and electrolyte losses persisted even when nothing was fed by mouth. There was no evidence of a hematological or consistent immunological defect in any infant and no abnormalities of intestinal hormones were noted. In the duodenal mucosa of all infants we saw similar abnormalities characterized by villus atrophy, crypt hypoplasia without an increase in mitoses or inflammatory cell infiltrate in the lamina propria and in villus enterocytes absence of a brush border, increase in lysosome-like inclusions, and autophagocytosis. In 3 infants studied by marker perfusion of the proximal jejunum we found abnormal glucose absorption and a blunted response of Na+ absorption to actively transported nonelectrolytes; in 2 there was net secretion of Na+ and H2O in the basal state. Our patients evidently suffered from a congenital enteropathy which caused profound defects in their capacity to assimilate nutrients. The similar structural lesion seen in the small intestinal epithelium of all of our cases undoubtedly contributed to their compromised intestinal function, but the pathogenesis of this disorder, if indeed it is a single disease, remains obscure.

Acidosis↗
PubMed1977

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.

Enteral Nutrition↗
PubMed1977

Synergistic infection with murine cytomegalovirus and Candida albicans in mice.

A previous report from this laboratory demonstrated that mice infected intraperitoneally with a 20% lethal inoculation of murine cytomegalovirus (CMV) exhibited markedly enhanced mortality rates (80%-100%) after an intravenous injection of a 0-20% lethal inoculum of Candida albicans. The current study revealed that mice infected with murine CMV alone had high titers of virus in spleen, liver, lung, and kidney from days 3 through 20, whereas those inoculated with C. albicans alone had a self-limited fungal infection involving only the kidney. In the combined murine CMV-C. albicans infection, the titers of murine CMV in tissues were changed very little. In contrast, C. albicans was recovered from multiple organs, and a progressive renal infection developed. This altered pathogenesis of the candida infection in murine CMV-infected mice resembled that produced by a 100% lethal inoculum of C. albicans alone. These results indicate that the murine CMV infection enhanced the susceptibility of mice to infection with C. albicans and suggest that death was due to progressive fungal infection of the kidney.

Animals↗
PubMed1977

Human rotavirus enteritis induced in conventional piglets. Intestinal structure and transport.

To better understand the pathogenesis of infantile viral gastroenteritis, we studied Na+ and Cl- fluxes in vitro in short-circuited jejunal epithelium from 8-10-day-old piglets after infection with a standard dose of human rotavirus given via nasogastric tube. 11 infected piglets, all of whom became ill, were compared with 9 uninfected, healthy litter-mates. When killed 72 h after infection, intestinal villi were shorter and crypts deeper (P less than 0.025) in duodenum, upper jejunum, and mid-small intestine, but not ileum in infected piglets. Virus antigen was seen by fluorescence microscopy in occasional jejunal villus tip cells in only four infected piglets and no controls at 72 h. Net Na+ and Cl- fluxes did not differ from noninfected litter-mate controls under basal conditions, but response to glucose was blunted in infected piglets (P less than 0.001). Theophylline stimulated net Cl- secretion in both infected and control animals, and cyclic AMP concentration in isolated jejunal villus enterocytes did not differ significantly. In isolated jejunal villus enterocytes of infected piglets, thymidine kinase activity increased (P less than 0.001), and sucrase activity decreased (P less than 0.001). We conclude that in this invasive enteritis caused by a major human viral pathogen, glucose-coupled Na+ transport is impaired in the jejunum at a time when the villus epithelium shows enzyme characteristics of crypt epithelium, and when little or no virus is present. These findings are identical to those occurring in an invasive coronavirus enteritis of piglets but differ markedly from those seen with enterotoxigenic diarrhea.

Animals↗
PubMed1977

Na+ transport in jejunal crypt cells.

As enterocytes migrate from crypts to villi they differentiate and mature. To examine the effect of epithelial differentiation on ion transport we studied 22Na+ efflux and (Na+--K+)-adenosine triphosphatase activity in suspensions of epithelial cells selectively isolated from different regions of the villus to compare crypt cells with villous tip cells. Enterocytes were isolated from rat jejunum by a dilation-vibration technique. Thymidine kinase, sucrase, and alkaline phosphatase activities were measured as markers of specific cell populations. Compared to villous cells, cells from the crypt region demonstrated lower (Na"--K+)-adenosine triphosphatase activity, lower total and passive Na+ efflux rate constants, and failure of Na+ transport to respond to an actively transported nonelectrolyte.

Adenosine Triphosphatases↗
PubMed1977

Acrodermatitis enteropathica, zinc, and the Paneth cell. A case report with family studies.

An infant with acrodermatitis enteropathica was studied before and after starting zinc therapy. Clinical recovery was rapid, and the plasma zinc, serum and mucosal alkaline phosphatase activities returned to normal. Light microscopy of small intestinal biopsies showed normal mucosa. Electron microscopy of the Paneth cells initially revealed abnormal inclusion bodies which disappeared during therapy, suggesting that the abnormality is secondary to zinc deficiency, and not a primary defect. These abnormal inclusions may represent altered secretory granules and a proliferation of lysosomes. We were unable to define the heterozygous state biochemically or histologically.

Acrodermatitis↗