Objective To compare the effect of two prebiotic/probiotic products on weight gain, stool microbiota, and stool short chain fatty acid content of premature infants. Methods This randomized, blinded, placebo-controlled trial included 90 premature infants treated with either a dietary supplement containing two lactobacillus species plus fructo-oligosaccharides (CUL, Culturelle®, ConAgra, Omaha, Nebraska, USA), a supplement containing several species of lactobacilli and bifidobacteria plus fructo-oligosaccharides (PBP, ProBioPlus DDS®, UAS Laboratories, Eden Prairie, Minnesota, USA), or placebo (a dilute preparation of Pregestamil formula) twice daily for 28 days or until discharge if earlier. The primary outcome was weight gain. Secondary outcomes were stool bacterial analysis by culture and 16S rDNA qPCR and stool short chain fatty acid content by high performance liquid chromatography. Results Both prebiotic/probiotic combinations contained more bacterial species than noted on the label. No significant effect on growth of either prebiotic/probiotic supplement was observed. By cultures, 64% of infants receiving PBP became colonized with bifidobacteria, compared to 18% of infants receiving CUL and 27% of infants receiving placebo (Chi Squared p=0.064). No differences were noted between groups in colonization rates for lactobacilli, Gram-negative enteric bacteria or staphylococci. By 16S rDNA PCR analysis, the bifidobacteria content in the stools of the infants receiving PBP was higher than in the infants receiving CUL or placebo (Kruskal-Wallis p=0.011). No significant differences in stool short chain fatty acid content were detected between groups. No adverse reactions were noted. Conclusions Infants receiving PBP were more likely to become colonized with bifidobacteria. No significant differences in weight gain or stool short chain fatty acid content were detected.

Prophylactic therapy with recombinant human lactoferrin and the probiotic, Lactobacillus GG, act to enhance defenses against invasive E. coli in the nascent small intestine. We suggest that rhLF and LGG are therapeutic agents that may reduce necrotizing enterocolitis and gut-related sepsis in preterm human infants.

A series of 84 patients with carcinoma of the larynx or hypopharynx was studied with regard to tumor host interaction. Prognostic evaluation of the “tumor” aspects of this interaction included preoperative staging (TNM), histologic grading of the primary tumor, and histologic examination for the presence of metastases confined to regional lymph nodes or extranodal spread. Morphological evidence of host resistance was judged by the presence and degree of lymphoid inflammatory infiltration around the primary tumor and factors suggestive of enhanced immune reactivity in lymph nodes, i.e., sinus histiocytosis, germinal center hyperplasia, plasmacytosis, and the presence of pyroninophilic blast cells. Of the factors evaluated, those which appeared to correlate best with 5‐year survival were stage of disease, presence or absence of positive regional nodes, histologic grade of the primary tumor, lymphoid infiltration in the primary tumor, and extensive germinal center hyperpiasia in the regional nodes. The favorable prognosis attached to the presence of lymphoid infiltration or germinal center hyperpiasia, however, was not uniform for all patients. The presence of lymphoid infiltration was a favorable sign only in the group of patients with positive nodes or in those patients with well‐differentiated (Grade I, II) tumors. The presence of extensive germinal center hyperpiasia was a favorable prognostic sign only in those patients with positive nodes or in those patients who had a poorly differentiated (Grade III, IV) tumor. None of the other morphological structures related to lymph node reactivity showed favorable prognostic significance. The relationship of morphology to host immune mechanisms was discussed.

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Antimicrobial proteins and peptides are key effectors of innate immunity at mucosal surfaces in adult animals (21), but their role in host defense during perinatal intestinal development is not clearly delineated. Paneth cells are specialized epithelia in the crypts of the small bowel that control the intestinal growth of bacterial pathogens through the secretion of antimicrobial proteins and peptides (11). Paneth cells secrete their antimicrobial-rich granules upon exposure to pathogenic bacteria and bacterial products (1,11,12), and alphadefensins account for 70% of the secreted bactericidal activity of Paneth cells (1).Neonatal necrotizing enterocolitis is a disease mainly of preterm human infants, but its pathogenesis is incompletely understood (8). It is hypothesized that abnormal bacterial colonization of the small bowel plays a role (3). A causative association between Paneth cells and necrotizing enterocolitis has been proposed because preterm infants inadequately express alpha-defensins in the small bowel (10). Additionally, Paneth cells in surgical specimens from human infants with necrotizing enterocolitis have a deficiency in lysozyme (4), a prominent antimicrobial protein in Paneth cell granules (11). The inability of neonatal Paneth cells to control the growth of bacterial pathogens in the lumen of the small bowel is an attractive hypothesis related to the initiation of necrotizing enterocolitis, but there is no in vivo evidence that Paneth cells provide host defense in the neonatal small bowel.This investigation postulated that ablating Paneth cells in neonatal rats would reduce the ability of the neonatal small bowel to clear an infection caused by enteroinvasive Escherichia coli. To test this hypothesis, dithizone was given systemically to neonatal rats. Since dithizone selectively destroys Paneth cells in adult rats (16), we quantified the effects of dithizone on the Paneth cells of neonatal rats. After dithizone treatment, newborn rats were infected with an intragastric dose of Escherichia coli, and the quantitative clearance of this bacterium from the small bowel lumen was measured.Effect of dithizone on Paneth cells in the noninfected neonatal small bowel. For studies that examined the effects of dithizone, specific-pathogen-free Sprague Dawley rats (Harlan, San Diego, CA) were studied between 4 and 5 days of age. The studies described below were approved by the Animal Use Committee of the University of California, Davis.Dithizone (Sigma-Aldrich, St. Louis, MO) was suspended in 25 mM Li 2 CO 3 buffer, stirred for 2 h at 37°C, and then filtered through preweighed Whatman 1 paper (Whatman Inc., Clifton, NJ). The filter paper was completely dried after filtration and was reweighed to determine the mg/ml of dissolved dithizone. The measurement of dissolved dithizone was used to properly dose administration of the dye.Three separate litters of 4-day-old pups were given an intraperitoneal (i.p.) injection of either filter-sterilized dithizone (75 mg/kg of body weight) in mM Li 2 CO 3 buffer, 25 mM...

Necrotizing enterocolitis (NEC) is a devastating disease of premature infants. Probiotics decrease the risk of NEC in clinical and experimental studies. Antimicrobial peptides protect the gut against noxious microbes and shape the commensal microbiota, but their role in NEC remains unclear. We report that like in human ontogeny, the rat pup has low expression of Paneth cell antimicrobials, which increases rapidly during normal development. To investigate the expression of antimicrobial peptides in experimental NEC and the impact of probiotics on their expression, premature rats were divided into three groups: dam fed (DF), hand fed with formula (FF), or hand fed with formula containing Bifidobacterium bifidum (FF+BIF). All groups were exposed to asphyxia and cold stress. The expression of lysozyme, secretory phospholipase A2, pancreatic-associated proteins 1 and 3 mRNA was elevated in the FF (NEC) group, compared to the DF and FF+BIF groups where disease was attenuated. We conclude that induction of antimicrobial peptides occurs in experimental NEC similar to that reported in human disease and is attenuated when disease is averted by probiotic B. bifidum. The induction of antimicrobial peptides is likely an adaptive mucosal response that is often not sufficient to prevent disease in the premature gut.

Large home-range size and habitat specificity are two commonly cited ecological attributes that are believed to contribute to species vulnerability. The eastern diamondback rattlesnake Crotalus adamanteus is a declining species that occurs sympatrically with the more abundant canebrake rattlesnake Crotalus horridus in a portion of the south-eastern Coastal Plain, USA. In this study, we use the ecological similarities of the two species as experimental controls to test the role of home-range size and habitat specificity in the imperilment of the eastern diamondback rattlesnake. We used analysis of variance to investigate differences in home-range size between the two species, and home-range selection was modeled as habitat use versus availability with a case control sampling design using logistic regression. We failed to detect differences in home-range size between the two species; therefore, we could not identify home-range size as an attribute contributing to the imperilment of eastern diamondback rattlesnakes. Eastern diamondback rattlesnakes selected pine savannas to a degree that suggests that the species is a habitat specialist. Of the two factors examined, habitat specificity to the imperiled longleaf pine ecosystem may be a significant contributor to the decline of the eastern diamondback rattlesnake.

Pediatric trainees did not seem to manifest burnout symptoms based upon the MBS; interviews suggested that some do experience significant stress, although manifestations and responses were varied, some may be at risk. Methods identifying individuals at risk for burnout, and interventions to cope with stress may be valuable to their training.