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Biomedical subjects

A N Neely

Publications and source records attributed to A N Neely.

At least 19 recordsLinked to original sources
PubMed2000

Survival of enterococci and staphylococci on hospital fabrics and plastic.

The transfer of gram-positive bacteria, particularly multiresistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE), among patients is a growing concern. One critical aspect of bacterial transfer is the ability of the microorganism to survive on various common hospital surfaces. The purpose of this study was to determine the survival of 22 gram-positive bacteria (vancomycin-sensitive and -resistant enterococci and methicillin-sensitive and -resistant staphylococci) on five common hospital materials: smooth 100% cotton (clothing), 100% cotton terry (towels), 60% cotton-40% polyester blend (scrub suits and lab coats), 100% polyester (privacy drapes), and 100% polypropylene plastic (splash aprons). Swatches were inoculated with 10(4) to 10(5) CFU of a microorganism, assayed daily by placing the swatches in nutritive media, and examining for growth after 48 h. All isolates survived for at least 1 day, and some survived for more than 90 days on the various materials. Smaller inocula (10(2)) survived for shorter times but still generally for days. Antibiotic sensitivity had no consistent effect on survival. The long survival of these bacteria, including MRSA and VRE, on commonly used hospital fabrics, such as scrub suits, lab coats, and hospital privacy drapes, underscores the need for meticulous contact control procedures and careful disinfection to limit the spread of these bacteria.

Anti-Bacterial Agents↗
PubMed1996

Recombinant neutral endopeptidase decreases oedema in the skin of burned guinea-pigs.

Oedema, due to increased vascular leakage postburn, cases significant problems for burn patients. The purpose of this study was to determine if local application of a recombinant neutral endopeptidase (rNEP) would reduce the increased vascular permeability caused by a burn. In a guinea-pig model, a single treatment of rNEP given immediately postburn significantly decreased burn-induced plasma extravasation. This rNEP effect was dependent upon both the dosage of the peptidase and its enzymatic activity. Additional experiments were consistent with the rNEP acting partly by degrading bradykinin, a mediator of increased vascular permeability postburn. These findings suggest that further study of rNEP as a possible treatment for oedema is warranted.

Analysis of Variance↗
PubMed1996

Circulating levels of tumour necrosis factor, interleukin 6 and proteolytic activity in a murine model of burn and infection.

Cytokines and proteinases have both been implicated as mediators in the inflammatory response associated with trauma and sepsis. Using a burned-infected mouse model, it was previously found that mortality is proportional to the amount of proteolytic activity (PA) in the circulation. However, little is known about circulating cytokine levels in hosts that are both burned and infected. With this mouse model, both tumour necrosis factor (TNF) and interleukin 6 (IL-6) were upregulated by a burn and by an infection. Burn plus infection produced an additive effect on each cytokine, but IL-6 levels correlated better with mortality. Treating mice with the proteinase inhibitor aprotinin immediately preburn and infectious challenge significantly decreased IL-6, PA and mortality. This may be a clinically relevant model for studying mediators in burned and/or septic hosts.

Animals↗
PubMed1995

Avirulence of a Pseudomonas aeruginosa algC mutant in a burned-mouse model of infection.

The virulence of wild-type Pseudomonas aeruginosa PAO1 and that of a genetically defined algC mutant, PAO1 algC::tet, were compared in a burned-mouse model of infection. Unlike PAO1, PAO1 algC::tet was avirulent, grew less well in the eschar, and did not disseminate to the liver of challenged animals. We have previously shown that the P. aeruginosa algC gene is required for biosynthesis of alginate and lipopolysaccharide (M.J. Coyne, Jr., K.S. Russell, C.L. Coyle, and J.B. Goldberg, J. Bacteriol. 176:3500-3507, 1994). In order to determine whether the alginate or lipopolysaccharide (LPS) defect was responsible for the avirulence of this strain, we constructed a strain with a mutation in an alginate-specific gene, algD. PAO1-algD was virulent in the burned-mouse model, thus implicating the LPS defect in PAO1 algC::tet as the relevant alteration responsible for the avirulence of this strain.

Animals↗
PubMed1994

Proteolytic activity and fatal gram-negative sepsis in burned mice: effect of exogenous proteinase inhibition.

Circulating proteolytic activity (PA) increases following burn or surgical trauma. Challenging traumatized mice with the yeast Candida albicans further increases PA. Once a PA threshold has been passed, mortality increases as PA increases. The purposes of this study were to determine (i) if gram-negative bacterial challenge affects circulating PA and mortality as Candida challenge does and (ii) if proteinase inhibitor treatment with aprotinin, antithrombin III, and alpha 1-proteinase inhibitor decreases circulating PA and increases the survival of burned mice infected with a bacterium. For all bacteria tested (Proteus mirabilis, Pseudomonas aeruginosa, and Klebsiella pneumoniae), burn plus challenge significantly elevated PA and mortality above levels in mice that were only burned or only challenged. Quantitative culture counts indicated that the mice died of sepsis. Proteinase inhibitor treatment of mice burned and challenged with K. pneumoniae significantly decreased circulating PA, decreased the hepatic microbial load, and increased survival. Hence, in traumatized mice challenged with either C. albicans or gram-negative bacteria, a relationship exists between proteolytic load and subsequent septic death. Parallels between these animal studies and human studies are discussed.

Animals↗
PubMed1992

Surgical trauma, Candida infection, and serum proteolytic activity.

Both surgical trauma and infection can disturb the proteinase to proteinase inhibitor balance in the circulation. We sought to assess the effect of Candida albicans infection (INFX) on postoperative mortality, to correlate mortality with total serum proteolytic activity (PA), and to assess the impact of exogenous proteinase inhibitors (PI) on this mortality. Mice underwent midline laparotomy (LAP) and immediate postoperative intravenous C. albicans infection. LAP + INFX shortened mean survival compared to INFX or LAP alone. Quantitative renal cultures confirmed that death in the LAP + INFX and INFX groups was due to Candida sepsis. PA was measured using an 125I-labeled protein assay, yielding micrograms of acid-soluble peptides/100 microliters of serum. In control, sham-operated, and LAP groups, PA averaged less than 9.0, and mortality was 0. In INFX and LAP + INFX groups, PA averaged greater than 14.5 and mortality was high. To determine if high PA was related to high mortality, LAP + INFX mice were treated immediately preoperatively with a single dose of PI (1 mg alpha 1-proteinase inhibitor, 1 mg antithrombin, and 1000 KIU aprotinin). Mean survival increased with PI treatment. In conclusion, the addition of Candida infection to surgical trauma hastened mean time to death. More rapid death correlated with elevated PA and may reflect systemic imbalance in the proteinase to proteinase inhibitor ratio in the circulation. PI improved survival, suggesting that proteinase inhibition may prove useful in the future in the treatment of fungal sepsis in surgical patients.

Animals↗
PubMed1992

Components of the increased circulating proteolytic activity in pediatric burn patients.

Total proteolytic activity (PA) is increased in the circulation of pediatric burn patients. The extent of the increase correlates with the percent total body surface area (TBSA) burned and is associated with increased susceptibility to fatal infection. To determine the source or sources of this PA, three factors were evaluated: (1) levels of proteinase inhibitors--antithrombin, alpha 2-antiplasmin, and alpha 1-proteinase inhibitor; (2) levels of proteinase--neutrophil elastase; and (3) activation of circulating proteolytic cascade systems as indicated by changes in levels of system components--plasminogen and prekallikrein. All assays measured functional levels of the proteins. Normal levels were determined in 25 consecutive well children who were seeing their pediatrician for checkups (14 boys, 11 girls, ranging in age from 10 months to 17 years). Twenty-five consecutive burn victims admitted to the Shriners Burns Institute, Cincinnati Unit (19 boys, six girls, aged 10 months to 17 years), with a mean full-thickness burn of 43.2% TBSA (range, 6%-87%) were studied in the first week postburn. Antithrombin, alpha 2-antiplasmin, plasminogen, and prekallikrein levels decreased (p < 0.001) postburn, whereas elastase increased (p < 0.001). We conclude that, in pediatric burn patients, decreased proteinase inhibitors, increased proteinase, and activation of circulating proteinase cascades all contribute to elevated total circulating PA postburn.

Adolescent↗
PubMed1992

Virulence and adhesive properties of serotypes A and B of Candida albicans isolated from paediatric burn patients.

The virulence and adhesive properties of 50 isolates of Candida albicans serotypes A and B collected over 6 years from 48 paediatric burn patients were examined to provide more detailed information about candidal pathogenesis in burn patients and to examine the relevance of the commonly used epithelial cell adhesion assay for determining fungal virulence. The isolates represented a fair distribution of serotypes (29 isolates were serotype A and 21 isolates were serotype B) and a total of 28 serotype-biotype combinations were found; 32% of the serotype-biotype combinations appeared only once, while 44% of the isolates showed similar biotype tests for two of three digits. Adhesion of the isolates to plastic and to buccal epithelial cells (BECs) was examined and compared after growth in a chemically defined medium. There were significant differences in the adhesion of individual isolates to plastic or BECs, but no correlation was found between biotype and adhesiveness. Serotype B isolates were found to be more adhesive to BECs (p less than 0.05) but not to plastic. There was no apparent correlation between candidal adhesiveness and site of isolation from these patients (autografts, blood, faeces, throat swabs, tracheal aspirates, wounds and intravenous catheters), although isolates from catheters were generally less adhesive to epithelial cells. Virulence in a systemic infection mouse model revealed that there were significant differences in virulence between isolates, but no correlation was found between virulence and the biotype, serotype or site of isolation. Similarly, no correlation was found between virulence and adhesiveness or cell-surface hydrophobicity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Effects of immunoglobulin G and low-dose amphotericin B on Candida albicans infections in burned mice.

Candidiasis causes serious problems for compromised hosts. Effective treatments for Candida albicans infections are few. To see if immunoglobulin (Ig) therapy could be beneficial, burn-immunocompromised mice were treated intravenously with 2.5 mg of five different IgG preparations 48 h postburn and post-C. albicans challenge. Despite up to fourfold differences in titer (1:1,600 to 1:6,400) to C. albicans, all preparations improved 10-day survival about 30% (P less than 0.0001). Treatment with a low dose of amphotericin B (AmB; 0.09 mg/kg of body weight) intravenously 24 and 48 h after burn and challenge improved survival 9 to 45% (P less than 0.0001). Treatment with a low dose of AmB plus IgG showed the same results as treatment with AmB alone and better results than treatment with IgG alone. Quantitative renal cultures from burned mice treated with AmB plus one IgG preparation, Sandoglobulin, showed that C. albicans counts decreased in sham-treated mice from 7.21 +/- 0.15 log10 CFU/g (mean +/- standard error of the mean) to 5.31 +/- 0.34, which was significantly less than counts with AmB (6.11 +/- 0.35) or Sandoglobulin (6.39 +/- 0.18) treatment alone. We conclude that (i) by using decreases in mortality and in renal fungal load as end points, treatment with IgG preparations alone or with a low dose of AmB alone protected burn-immunocompromised mice from candidiasis; (ii) though AmB plus one IgG preparation significantly decreased renal fungal load, the combination did not significantly decrease mortality beyond that found with AmB alone; and (iii) survival data did not correlate with IgG titers to C. albicans.

Amphotericin B↗
PubMed1992

Hageman factor dependent activation and its relationship to lethal Pseudomonas aeruginosa burn wound infections.

Trauma causes increases in total protease load in the circulation of the traumatized host animal or patient. This increase is due, in part, to Hageman Factor activation followed by down-line cascade system activation. Concomitant with the activation of these systems is a reduced host capacity to resist infection. Infection superimposed on a traumatized host increases the total host protease load even more by additional activation of Hageman Factor and cascade systems.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1991

Effect of challenge with Candida albicans strains with different levels of virulence on plasma proteins in burned mice.

Immunoglobulin G, immunoglobulin A, transferrin, and fibrinogen were measured by radial immunodiffusion in plasma samples from burned versus unburned mice challenged with high-virulence Candida albicans MY 1044 or its low-virulence mutant, MY 1049. Early decreases in these proteins were found after burn and/or MY 1044 but not MY 1049 challenge. These decreases may contribute to increased susceptibility of mice that were burned and challenged by MY 1044 to lethal candidiasis.

Animals↗