Biomedical subjects

Andrew B Onderdonk

Publications and source records attributed to Andrew B Onderdonk.

5 recordsLinked to original sources

PubMed2003

Protection against lethal intra-abdominal sepsis by 1-(3-dimethylaminopropyl)-3-ethylurea.

Sodium hyaluronate-carboxymethylcellulose (HA/CMC) formulations are gels that effectively reduce postoperative adhesions in both animals and humans, when placed in the peritoneal or pelvic cavities concomitant with surgical manipulation. However, it has been suggested that the use of these products may increase the risk of peritoneal infection after contamination with intestinal contents during surgery. Using the rat intra-abdominal sepsis model, we found that administration of HA/CMC gels before bacterial challenge did not increase mortality but did significantly protect rats against lethal infection. This effect was dose and time dependent. Protection was conferred not by the HA/CMC gels themselves but by 1-(3-dimethylaminopropyl)-3-ethylurea (EDU), a small molecule released from the gel complex under physiologic conditions. Our results suggest that the protective effect exhibited by EDU is related to down-regulation of T cell-dependent responses and suppression of the proinflammatory-cytokine cascade associated with mortality during the early phase of disease.

Abdominal Abscess↗

PubMed2003

Method for optimizing pulsed-field gel electrophoresis banding pattern data.

The genomic DNA of 47 strains of TSST-1 toxin-producing Staphylococcus aureus were cleaved with SmaI restriction endonuclease and resolved in an agarose gel by pulsed-field gel electrophoresis (PFGE). An algorithm was designed to standardize the band weights or brightness (trace quantity) produced to a bounded region between 0 and 1 regardless of DNA fragment size while simultaneously reducing gel-to-gel variability. The algorithm allows for classification of isolates by band intensity as well as DNA mobility without a numerical hierarchy of band intensity that is caused by ranging DNA fragment lengths. On analysis many isolates were classified as separate entities on the basis of DNA co-migration only. Isolates differing by only DNA co-migration were subjected to a second digestion with restriction enzyme SacII. These isolates were characterized similarly to the standardized trace quantity analysis of SmaI PFGE patterns. The standardization method proposed in this article permits characterization of isolates on the basis of band differences, regardless of DNA co-migration, thus increasing the discriminatory power (0.79 to 0.89) of PFGE by increasing band-associated information. An established unbiased approach to the partitioning of data were also explored.

Algorithms↗

PubMed2003

Wound fluid bacterial levels exceed tissue bacterial counts in controlled porcine partial-thickness burn infections.

In the present study, an established controlled burn wound model was used to test the hypothesis that controlled surface contamination with is capable of generating a noninvasive method for the creation of a reproducible deep tissue burn wound infection. Using a liquid tight-wound chamber in Yorkshire pigs, partial-thickness burns were inoculated with saline-immersed for 24 hours. Noninoculated burns and unwounded skin immersed in normal saline served as controls. Bacterial cultures of wound fluid were performed daily, and tissue biopsies for bacteriological and histological evaluations were performed on days 1, 3, and 5. was only recovered from -inoculated wounds (tissue and fluid), whereas all controls contained endogenous only. The number of colony-forming units per gram of wound tissue did not correlate with the bacterial counts found in the overlying wound fluid for any wounds. Fluid counts were consistently higher than tissue counts by two logs. -inoculated wounds showed three times deeper tissue destruction than control wounds. Obtaining consistently deep tissue colonization without cross-contamination among wounds, this study introduces a noninvasive model for controlled burn wound infection suitable for future investigations regarding the efficacy of topical antibiotic wound treatment in experimental burns.

Animals↗

PubMed2003

Quantitative microbiologic models for preterm delivery.

Preterm delivery (PTD) is the leading cause of infant morbidity and mortality in the United States. An epidemiological association between PTD and various bacteria that are part of the vaginal microflora has been reported. No single bacterial species has been identified as being causally associated with PTD, suggesting a multifactorial etiology. Quantitative microbiologic cultures have been used previously to define normal vaginal microflora in a predictive model. These techniques have been applied to vaginal swab cultures from pregnant women in an effort to develop predictive microbiologic models for PTD. Logistic regression analysis with microbiologic information was performed for various risk groups, and the probability of a PTD was calculated for each subject. Four predictive models were generated by using the quantitative microbiologic data. The area under the curve (AUC) for the receiver operating curves ranged from 0.74 to 0.94, with confidence intervals (CI) ranging from 0.62 to 1. The model for the previous PTD risk group with the highest percentage of PTDs had an AUC of 0.91 (CI, 0.79 to 1). It may be possible to predict PTD by using microbiologic risk factors measured once the gestation period has reached the 20-week time point.

Bacteria↗

PubMed2002

CD1d-dependent macrophage-mediated clearance of Pseudomonas aeruginosa from lung.

CD1d-restricted T cells are implicated as key players in host defense against various microbial infections. However, the mechanisms involved and the role they play, if any, at the mucosal surfaces where pathogenic infections are initiated is unknown. In a murine pneumonia model established by intranasal application of Pseudomonas aeruginosa, CD1d(-/-) mice showed markedly reduced pulmonary eradication of P. aeruginosa compared with wild-type mice; this was associated with significantly lower amounts of macrophage inflammatory protein-2 and reduced numbers of neutrophils within the bronchoalveolar lavage fluid. Corollarily, treatment of mice with alpha-galactosylceramide--a lipid that activates CD1d-restricted T cells--increased the amount of interferon-gamma; this was associated with rapid pulmonary clearance through enhanced phagocytosis of P. aeruginosa by alveolar macrophages. These results reveal a crucial role played by CD1d-restricted T cells in regulating the antimicrobial immune functions of macrophages at the lung mucosal surface.

Animals↗