Delayed but effective treatment of red-back spider envenomation.
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Adult↗
Biomedical subjects
C L Wells
Publications and source records attributed to C L Wells.
Bacterial translocation in a large-animal model of small-bowel transplantation. Portal vs systemic venous drainage and the effect of tacrolimus immunosuppression.
OBJECTIVE: To study whether bacterial translocation is more prevalent after small-bowel transplantation with systemic venous drainage (SVD) vs portal venous drainage (PVD) and whether it is influenced by immunosuppression. DESIGN: We performed 15 small-bowel transplantations in pigs. Group 1 (n = 5) had SVD and no immunosuppression; group 2 (n = 6), PVD and no immunosuppression; and group 3 (n = 4), PVD and immunosuppression with tacrolimus and methylprednisolone sodium succinate. Portal and systemic blood, portal and mesenteric lymph nodes, and liver were cultured in donors and recipients on postoperative day 0 (POD 0) and in recipients on postoperative day 3 (POD 3). Jejunal and ileal contents were also sampled at these times. SUBJECTS: Outbred male Yorkshire-Landrace pigs. MAIN OUTCOME MEASURES: (1) Blood and tissue bacterial cultures, (2) blood endotoxin levels, and (3) histopathologic examination. RESULTS: Cultures were positive for bacteria in 32% (16/50) of samples on POD 0 and 88% (22/25) on POD 3 in group 1, in 18% (11/60) of samples on POD 0 and 97% (29/30) on POD 3 in group 2, and in 8% (3/40) of samples on POD 0 and 95% (19/20) on POD 3 in group 3. Systemic blood cultures were positive for bacteria on POD 3 in 60% (3/5) of pigs in group 1, 83% (5/6) in group 2, and 100% (4/4) in group 3. Significantly more bacteria were present in the ileum than in the jejunum on POD 0 in group 2; this difference approached significance in groups 1 and 3. Bacterial numbers were identical in the ileum and jejunum by POD 3 in all groups. Circulating endotoxin levels were significantly elevated on POD 3 vs POD 0 only in group 1. Endotoxin levels were not significantly different between the SVD group (group 1) and either PVD group (groups 2 and 3). CONCLUSIONS: Bacterial translocation is prevalent after small-bowel transplantation in pigs whether PVD or SVD is used. Immunosuppression with tacrolimus does not prevent bacterial translocation but may reduce systemic endotoxemia.
Animals↗
Surgical Infection Society position on vancomycin-resistant Enterococcus.
The risk of transfer of vancomycin resistance to staphylococci is a real possibility and has been achieved in the laboratory. Prolonged colonization occurs with vancomycin-resistant Enterococcus (VRE), and many more patients are colonized than infected. The failure to identify, isolate, and adhere to infection control measures when caring for VRE-colonized patients dooms to failure any means to control its spread. Control of vancomycin use alone is unlikely to greatly affect the number of patients at risk for VRE colonization. The global spread of VRE may be impossible to stop, but infection control measures are the most important line of defense inside hospitals.
Anti-Bacterial Agents↗
Problems and priorities for controlling opportunistic pathogens with new antimicrobial strategies; an overview of current literature.
An International Study Group on New Antimicrobial Strategies (ISGNAS) has been formed in response to the recognition that development of microbial resistance to antibiotics is becoming a serious, world-wide problem. The group met in 1993 for the first time to discuss the feasibility of developing rational alternatives to the use of antibiotics and prepared, as a result, a comprehensive overview of normal (physiological) mechanisms involved in the control of potentially pathogenic (oppotunistic) microorganisms. One objective of ISGNAS is to understand the conditions which allow opportunistic microbes present among the symbionts to cause an infection. There is a need for more coherent information concerning the habitat, growth requirements and host and pathogen properties which allow opportunistic pathogens to cause life-threatening infections. In particular, information is urgently being sought to understand the complexity of the interactions between the vast number of microbial species, and the interactions between the microbes and their host. Another goal is to inspire and enable basic and clinical research that will lead to the development of new therapies for regulating colonization, translocation and infection by opportunistic micro-organisms in patients during periods of decreased resistance. With a sufficient amount of knowledge of how healthy individuals keep opportunistic micro-organisms under control, it may become feasible for physicians to maintain host resistance and inter-microbial factors involved in the containment of opportunistic microbes. Therapies aimed at boostering natural resistance mechanisms will be of critical importance to individuals whose resistance has been compromised as a result of another clinical condition.
Adjuvants, Immunologic↗
Bacteroides fragilis enterotoxin modulates epithelial permeability and bacterial internalization by HT-29 enterocytes.
BACKGROUND & AIMS: Enterotoxigenic Bacteroides fragilis has been associated with diarrheal disease, and the enterotoxin has a cytopathic effect on cultured HT-29 enterocytes. Experiments were designed to determine the effect of B. fragilis enterotoxin on bacteria-enterocyte interactions. METHODS: Confluent HT-29 enterocytes were incubated for 1 hour with B. fragilis enterotoxin, followed by 1 hour of incubation with pure cultures of enteric bacteria, namely, Salmonella typhimurium (two strains), Listeria monocytogenes (three strains), Proteus mirabilis, Escherichia coli (three strains), and Enterococcus faecalis. Enterocyte viability was assessed using vital dyes, epithelial permeability was measured using transepithelial electrical resistance, enterocyte morphology and bacteria-enterocyte interactions were visualized using light and electron microscopy, and bacterial internalization was assessed using a quantitative culture of lysed enterocytes. RESULTS: B. fragilis enterotoxin did not affect enterocyte viability but decreased transepithelial electrical resistance, and individual enterocytes pulled apart. Enterotoxin pretreatment decreased internalization of L. monocytogenes (P < 0.01) but increased (P < 0.01) internalization of the other strains of enteric bacteria. Augmented bacterial internalization was associated with preferential bacterial adherence on the exposed lateral surface of enterotoxin-treated enterocytes. CONCLUSIONS: B. fragilis enterotoxin was associated with HT-29 cell rounding and with augmented internalization of selected strains of enteric bacteria that were preferentially adherent on the exposed enterocyte lateral surface.
Bacterial Adhesion↗
Effect of hypoxia on enterocyte endocytosis of enteric bacteria.
OBJECTIVE: To clarify the effect of hypoxia on bacteria-enterocyte interactions. DESIGN: Randomized. SETTING: Research laboratory. SUBJECTS: Enteric bacterial and cultured human intestinal epithelial cells, HT-29 cells. INTERVENTIONS: The effect of hypoxia on bacterial internalization and intracellular survival was studied, using enterocytes cultured for 21 days in either 20%, 10%, or 5% oxygen. The effect of bacterial growth conditions on bacterial internalization by enterocytes was studied, using bacterial cells in either the log phase or stationary phase of aerobic growth, and using bacterial cells in stationary phase, grown either under low oxygen conditions or under anaerobic conditions. MEASUREMENTS AND MAIN RESULTS: Individual strains of enteric bacteria were incubated with HT-29 cells for 1 hr. Numbers of internalized bacteria were subsequently quantified after enterocyte lysis. Bacterial growth conditions (anaerobic vs. aerobic and log-phase vs. stationary-phase bacterial cells) had no noticeable effect on the numbers of Salmonella typhimurium, Proteus mirabilis, and Escherichia coli internalized by enterocytes. Enterocytes cultivated in 20%, 10%, or 5% oxygen were >95% viable. Enterocytes cultivated in 20% oxygen were confluent, but those enterocytes cultivated in hypoxia were not confluent and were fewer in number compared with enterocytes cultivated in normoxia. Compared with enterocytes grown in normoxia, enterocytes cultivated in 5% and 10% oxygen internalized greater numbers of each of seven strains of enteric bacteria, including Listeria monocytogenes (two strains), Enterococcus faecalis (two strains), and P. mirabilis, E. coli (two strains), with statistically significant increases noted for five of these seven bacterial strains. Intracellular survival of L. monocytogenes and P. mirabilis was assayed. Both species survived intracellularly for 22 hrs, with no noticeable differences in the numbers of intracellular bacteria recovered from enterocytes cultivated in 20%, 10%, and 5% oxygen. CONCLUSION: These in vitro results suggest that augmented bacterial endocytosis by enterocytes might at least partially explain the increased frequency of bacterial translocation associated with tissue ischemia.
Bacterial Translocation↗
Does physical activity reduce risk of estrogen-dependent cancer in women?
The estrogen-dependent cancers (breast, endometrial, and ovarian) are among the leading causes of morbidity and mortality in American women. Increased incidence of these cancers is predicted in the future, and the need for primary prevention is clear. Sufficient evidence has accumulated to warrant an analysis of the relationship between physical activity and estrogen-dependent cancer. Recent epidemiological studies confirm an inverse relationship between physical activity and estrogen-dependent cancer, with stronger associations appearing for occupational activity than for leisure time or nonoccupational activity. Several hypothesized mechanisms are described for the prevention of estrogen-dependent cancer by physical activity: 1) maintenance of low body fat and moderation of extraglandular estrogen, 2) reduction in number of ovulatory cycles and subsequent diminution of lifetime exposure to endogenous estrogen, 3) enhancement of natural immune function, and 4) the association of other healthy lifestyle habits. Although the mechanisms are not well defined, several lines of evidence support the inclusion of low-to-moderate physical activity as a preventive strategy for estrogen-dependent cancer.
Breast Neoplasms↗
Intracellular survival of enteric bacteria in cultured human enterocytes.
Translocating enteric bacteria have been visualized within intact intestinal epithelial cells in animal models of bacterial translocation. Although the ability of the enterocyte to engulf bacteria has been well documented in both in vivo and in vitro experimental models, relatively little is known about the enterocyte's ability to degrade internalized bacteria. Intracellular survival of eight strains of enteric bacteria (two strains of Listeria monocytogenes, Salmonella typhimurium, Proteus mirabilis, two strains of Escherichia coli, and two strains of Enterococcus faecalis) was quantified over a 20 h period using two different types of terminally differentiated polarized enterocytes considered relevant in vitro models of human small intestinal epithelium, namely Caco-2 and HT-29 cells. Caco-2 enterocytes were generally more permissive for bacterial uptake when compared with HT-29 enterocytes. However, bacterial survival was similar within each type of enterocyte, and most strains of enteric bacteria remained viable within enterocytes for the 20 h duration of the assay. In addition, with the exception of one strain of L. monocytogenes in Caco-2 cells, intracellular enteric bacteria had no noticeable effect on host enterocyte viability for this 20 h duration. Transmission electron microscopy was used to visualize both intact and degraded bacteria within individual enterocytes, suggesting that prolonged bacterial survival might have resulted from simultaneous bacterial degradation and replication. Thus, although enterocytes internalize enteric bacteria, enterocytes might not kill internalized bacteria as efficiently as leukocytes. Observations of bacterial intracellular survival supported the hypothesis that the enterocyte might be a portal of entry for translocating microbes, and observations of intracellular bacterial degradation might have implications for the role of the enterocyte as an antigen-presenting cell.
Caco-2 Cells↗
Colonization and translocation of intestinal bacterial flora.
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Animals↗
Stool carriage, clinical isolation, and mortality during an outbreak of vancomycin-resistant enterococci in hospitalized medical and/or surgical patients.
During a nosocomial outbreak of infection due to vancomycin-resistant enterococci (VRE), rectal swabs that were collected weekly were used to identify and isolate VRE carriers. Over 6 months, 1,458 stool specimens from 724 high-risk patients were cultured, and 187 VRE isolates were recovered from 61 patients; 96% of the isolates were Enterococcus faecium. VRE tended to be isolated from clinical specimens from patients identified as VRE carriers by stool surveillance (P < .01). However, isolation of VRE from surveillance cultures preceded clinical isolation for only approximately 50% of the patients from whom a clinical VRE isolate was recovered. Mortality was greater (P < .05) among patients from whom a clinical VRE isolate was recovered than among patients from whom VRE was isolated only by stool surveillance. The mortality (1[17%] of 6) among patients for whom VRE was isolated from blood was similar to that (10 [27%] of 37) among patients for whom vancomycin-susceptible enterococcus was isolated from blood (P = .97). Despite prompt initiation of contact precautions for VRE carriers, the incidence of fecal carriage of VRE remained approximately 8% among this patient population for the 6-month period of the study.
Adult↗
Inhibitory effect of bile on bacterial invasion of enterocytes: possible mechanism for increased translocation associated with obstructive jaundice.
OBJECTIVE: To clarify the effect of bile salts on internalization of enteric bacteria by intestinal epithelial cells. DESIGN: Randomized study. SETTING: Research laboratory. SUBJECTS: Cultured human intestinal epithelial cells, namely HT-29 cells. INTERVENTIONS: The effect of bile was studied by adding bile during the time period in which bacterial cells were permitted to interact with enterocytes. In subsequent experiments, bile was added to the culture medium used to grow bacteria, and bacterial cells were washed before adding bacteria to enterocytes. Three different concentrations of three different bile preparations were tested. MEASUREMENTS AND MAIN RESULTS: Salmonella typhimurium and Proteus mirabilis were each incubated with HT-29 cells for 1 hr; the numbers of internalized bacteria were subsequently quantified following enterocyte lysis. The presence of bile during bacteria-enterocyte incubation had no effect on the numbers of internalized bacteria. However, if S. typhimurium or P. mirabilis were grown in the presence of bile, these washed bacterial cells were generally internalized by HT-29 cells in significantly fewer numbers, compared with bacterial cells grown in medium without bile supplementation. Enterocyte viability and morphologic ultrastructure did not appear to be affected by the presence of bile itself, or by the interaction with bacterial cells that had been cultivated in unsupplemented medium or in bile-supplemented medium. CONCLUSIONS: Exposure to bile during bacterial growth resulted in bacterial cells with decreased invasiveness for cultured intestinal epithelial cells. This observation is consistent with previous in vivo studies of obstructive jaundice, where the absence of bile in the intestinal lumen, not bile duct ligation, appeared to facilitate bacterial translocation in obstructed animals. Thus, the presence of bile in the intestinal lumen may decrease bacterial translocation by a mechanism that involves decreased epithelial internalization of enteric bacteria.
Bile↗
Exposure of the lateral enterocyte membrane by dissociation of calcium-dependent junctional complex augments endocytosis of enteric bacteria.
Intestinal bacterial translocation is facilitated in a variety of clinical conditions involving increased intestinal permeability, such as shock and trauma. Because there is both in vivo and in vitro evidence that enteric bacteria can be internalized by intestinal epithelial cells, experiments were designed to test the effect of increased intestinal permeability on enterocyte endocytosis of enteric bacteria. Mature, confluent cultures of HT-29 enterocytes were placed in a calcium-free solution for 1 h. Enterocyte viability was not noticeably altered, but transepithelial electrical resistance was significantly decreased (indicating a decrease in epithelial junctional integrity), and the enterocytes were pulled apart. Electron microscopic observations revealed enteric bacteria preferentially adherent on the exposed enterocyte lateral surface, and the numbers of viable enteric bacteria (Listeria monocytogenes, Salmonella typhimurium, Proteus mirabilis, Escherichia coli, and Enterococcus faecalis) internalized by these enterocytes were significantly increased. Restoration of calcium restored confluency to enterocyte cultures, and bacterial internalization reverted to control levels. Thus, calcium-dependent junctional integrity might play a role in augmenting bacterial translocation in clinical conditions associated with increased intestinal permeability.
Animals↗
Contact with epithelial cells induces the formation of surface appendages on Salmonella typhimurium.
The enteric bacteria Salmonella typhimurium has the ability to invade (enter) nonphagocytic cells. The internalization process occurs as a result of an intimate interaction between the bacteria and the host cell, in which S. typhimurium triggers a cascade of host cell-signaling events leading to the formation of host cell membrane ruffles and bacterial uptake. Using high resolution scanning electron microscopy, we have observed that contact with cultured epithelial cells results in the formation of appendages on the surface of S. typhimurium. The formation of such appendages did not require de novo protein synthesis, and it was transient, since these surface structures were no longer present on bacteria that had initiated the internalization event. Salmonella mutants defective in the transient formation of these surface organelles were unable to enter into cultured epithelial cells, indicating that such structures are required for bacterial internalization.
Animals↗
A plasmid-encoded surface protein on Enterococcus faecalis augments its internalization by cultured intestinal epithelial cells.
Aggregation substance, a plasmid-encoded Enterococcus faecalis surface protein, plays a role in mediating the formation of mating aggregates, resulting in plasmid transfer. The role of aggregation substance in the internalization of E. faecalis by cultured intestinal epithelial cells, namely HT-29 cells, was analyzed. It was associated with a significant increase in endocytosis of E. faecalis by HT-29 cells: Numbers of internalized enterococci were fewer than of an invasive strain of Listeria monocytogenes, similar to Salmonella typhimurium and another L. monocytogenes strain, and greater than relatively noninvasive strains of E. faecalis, Proteus mirabilis, and Escherichia coli. Electron microscopy confirmed aggregation substance on the surface of strains interacting with the enterocyte microvillous surface, and intracellular enterococci were localized within membrane-bound vacuoles in the enterocyte cytoplasm. Thus, aggregation substance may facilitate E. faecalis internalization by host epithelial cells.
Bacterial Adhesion↗
Bacterial translocation and lipopolysaccharide-induced mortality in genetically macrophage-deficient op/op mice.
Genetically macrophage-deficient op/op mice have a total absence of macrophage colony-stimulating factor (also known as colony-stimulating factor 1 or CSF-1), and therefore an absence of a population of macrophages dependent on CSF-1. op/op mice also have profound secondary deficiencies in certain cytokines secreted by this macrophage population, such as tumor necrosis factor, interleukin-1, and granulocyte colony-stimulating factor. In the present study, op/op mice were used to clarify the role of the macrophage in two clinical processes: (a) bacterial translocation in response to antibiotic-induced intestinal overgrowth, and (b) endotoxin-induced bacterial translocation, morbidity, and mortality. The results were unexpected, in that bacterial translocation and endotoxin-induced morbidity and mortality were similar in op/op mice and their functionally normal littermates. These data indicated either that a specific macrophage population and its cytokines (including tumor necrosis factor and interleukin 1) might not play pivotal roles in the pathogenesis of bacterial translocation and endotoxin-induced septic shock, or alternatively, as yet unknown redundancies in vivo might compensate for the genetic deficiencies associated with the op/op mutation.
Animals↗
Bacterial translocation in cultured enterocytes: magnitude, specificity, and electron microscopic observations of endocytosis.
Previous in vivo evidence has shown that bacterial phagocytosis by enterocytes may be an initial step in bacterial translocation across the intestinal epithelium. This study analyzed the interactions of cultured enterocytes, namely Caco-2 cells, with nine strains of enteric bacteria, tested in pure culture and in mixed culture. These nine strains had a spectrum of invasive potential and included Salmonella typhimurium, Listeria monocytogenes (three strains), Escherichia coli (three strains), Proteus mirabilis, and Enterococcus faecalis. Numbers of viable intracellular bacteria recovered from Caco-2 cells were: L. monocytogenes > S. typhimurium > P. mirabilis > E. coli > E. faecalis. Uptake of a given microbe by enterocytes was strain-specific and was not influenced by the presence of another strain, regardless of the invasive ability of the coinfecting strain. Electron microscopic visualization of bacterial adherence and uptake by Caco-2 cells indicated that the epithelial interactions of normal enteric bacteria were similar to these observed with invasive strains of salmonella and listeria.
Bacteria↗
The use of heart rates to monitor exercise intensity in relation to metabolic variables.
Exercise intensity during training and competition was assessed in women runners in relation to two metabolic markers determined in the laboratory, ventilatory threshold (VT) and 4 mM of blood lactic acid (OBLA). Heart rates (HRs) were then obtained during 6 days of training and during an 8 km race. These HRs were used as references for quantifying the amount of hard (> HR-OBLA), moderate (< HR-OBLA, > HR-VT) and easy (< HR-VT) intensity training. Mean maximal heart rate (HRmax) was 183 bpm, HR-OBLA was 94.8% of HRmax, and HR-VT was 82.2% of HRmax. Average weekly training time was 301.2 min, of which 45.8% was in the easy intensity range, 45.7% in the moderate intensity range, and 8.9% in the hard intensity range. Self-reports of how training time was spent differed from actual training as revealed by the monitored heart rates. Subjects reported that they completed 3 sessions per week of easy intensity training, less than 1 session of moderate intensity training, and 1.5 sessions of hard intensity training. More than 70% of the 8 km race was performed at an intensity higher than HR-OBLA (173 bpm). Although 8 km race intensity closely corresponded with that at OBLA, very little training time was spent at that running intensity. HR monitoring of training intensity provided more accurate information than self-reports of training intensity.
Adult↗
Editorial response to a decade of experience with selective decontamination of the digestive tract as prophylaxis for infections in patients in the intensive care unit: what have we learned?
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Anti-Bacterial Agents↗