The future of health care--a community concept. Newfoundland.
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Biomedical subjects
Publications and source records attributed to H Collins.
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Fifteen hundred patients were scanned to predict fetal age and weight by biparietal diameter measurement. three hundred eleven patients had more than one scan. Forty-three small for gestational age (SGA) babies were ultimately delivered in this population. Prenatal ultrasound screening criteria for grouping into appropriate for gestational age (AGA) or small for gestational age (SGA) categories were: a) only an absolute biparietal diameter below the third percentile for the reference Rochester region population; b) only delta BPD calculated as less than 50 percent of the mean growth rate for the reference population; and c) a combination of these two factors. Intrauterine growth retardation was most accurately determined when an absolutely small biparietal diameter was found (at the time of the last ultrasound examination) in a woman with accurate gestational age assessment. Least accurate was the prediction based on one biparietal diameter measurement in a woman with poor clinical dates. A 50 percent false positive detection rate and poor sensitivity to intrauterine growth retardation were found using ultrasound biparietal diameter measurements as a screening test in this manner.
The mechanisms whereby invasive enteropathogens, e.g., Salmonella typhimurium, induce intestinal secretion are largely unknown. Since these organisms penetrate the intestinal epithelium, disrupt the brush border, and evoke an acute inflammatory reaction, increased plasma filtration through a damaged, more permeable epithelium might contribute to the secretory process. To examine this possibility, the plasma-to-lumen clearance of two different sized molecules, [51Cr]albumin and [14C]mannitol, was measured in the in vivo rabbit ileal loop and in vivo rhesus monkey models of salmonellosis. In the rabbit ileal loop model, the clearance of neither molecule was increased when compared to cholera toxin-exposed loops. In the rhesus monkey, clearance of [14C]mannitol into the jejunum, ileum, and colon of Salmonella-infected animals did not differ from the observed in control animals. These data indicate that invasion of the intestinal mucosa by S. typhimurium has not substantially altered the permeability characteristics of the intestinal mucosa and that plasma filtration through a damaged, more permeable mucosa does not contribute to the Salmonella-induced intestinal secretory process.
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Strains of Salmonella typhimurium were studied in the ligated rabbit ileal loop model to gain insight into the mechanisms whereby bacteria which invade the gastrointestinal mucosa evoke fluid exsorption. The organisms employed differed in various biologic attributes including the ability to invade the ileal epithelium, multiply within the mucosa, elicit an acute inflammatory reaction, and disseminate across the intestinal wall. Some strains provoked small intestinal fluid exsorption although these did not elaborate enterotoxin. Only those strains which invaded the mucosa were accompanied by either mucosal inflammation or fluid exsorption. Noninvasive strains produced neither histologic abnormalities nor fluid secretion. While strains which invaded the mucosa caused an acute inflammatory reaction, not all such strains evoked fluid secretion. Furthermore, there was no correlation in ability of invasive organisms to evoke fluid secretion or in the intensity of mucosal inflammation, number of intramucosal salmonellae, or in ability to disseminate from the rabbit ileum. These observations suggest that, as is the case in shigellosis, mucosal invasion may be a necessary factor for the intestinal fluid loss in salmonellosis. A bacterial property or factor, in addition to invasion of the gastrointestinal mucosa, seems to be responsible for fluid exsorptin. However, it is unlikely that a salmonella enterotoxin comparable to that elaborated by Vibrio cholerae, toxigenic Escherichia coli, or Shigella dysenteriae 1 is related to fluid secretion in salmonellosis.
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We have prepared aminoethyl (AE), aminopropyl (AP), and aminopentyl (APT) derivatives of gentiobiose heptaacetate (GH). These spacer compounds (AEGH, APGH, APTGH) have been coupled to succinylated diphtheria toxoid (Suc.DT) to produce conjugate vaccines. These conjugates all bind to the anti-lipid A human monoclonal antibody A6(H4C5) in an ELISA binding assay. Rabbits immunized with the APGH conjugate vaccine in either Freund's complete adjuvant or aluminum hydroxide gel produced antibody levels of 5120 and 3600 ELISA units, respectively, compared to an antibody level of less than 20 ELISA units for the prebleed sera. Sera from mice immunized with either the aminopropyl or the aminopentyl conjugate had antibody levels of 5120 and 2560 ELISA antibody units, respectively. These antibodies neutralized endotoxin in a Limulus lysate neutralization assay. Protection against the local Shwartzman reaction was demonstrated (p less than 0.05) in eight out of nine rabbits immunized with the Suc-DT-APGH conjugate vaccine compared to three out of 10 rabbits immunized with the carrier protein Suc-DT. Passive transfer experiments demonstrated that four out of five rabbits receiving immune serum were protected from Shwartzman reaction compared to one out of five rabbits receiving normal serum (p less than 0.1). These results indicated that epitopes contained in gentiobiose heptaacetate when properly presented as conjugate vaccines were capable of inducing neutralizing antibodies against endotoxin.