The ethics of pharmaceutical promotion.
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Advertising↗
Biomedical subjects
R J Hamill
Publications and source records attributed to R J Hamill.
Phagocytosis of Staphylococcus aureus by cultured bovine aortic endothelial cells: model for postadherence events in endovascular infections.
We examined the interaction of Staphylococcus aureus with cultured bovine aortic endothelial cells as a model for the initial events in the pathogenesis of endovascular infections. Confluent monolayers of cultured endothelial cells were incubated with S. aureus. Cell-associated bacteria were measured by washing away nonadherent organisms, disrupting the monolayers, and performing quantitative cultures. Phagocytosis was differentiated from adherence by treating the cells with lysostaphin; approximately 60% of cell-associated bacteria was found to be intracellular. Phagocytosis could be blocked by using cytochalasin B, which interferes with microfilament function. Addition of fibronectin resulted in a 63% increase in adherence of S. aureus to the endothelial cells but did not increase ingestion. Transmission electron microscopy demonstrated a sequence of events similar to that which occurs during ingestion by professional phagocytes, including: adherence of bacteria to the endothelial cell; formation and elongation of surface extensions of the endothelial cell to surround the adherent bacteria; and complete enclosure within apparent phagosomes. Phagocytosis of bacteria by endothelial cells, followed by intracellular persistence, may be an important postadherence event in the pathogenesis and pathophysiology of endovascular infections.
Animals↗
Effects of subinhibitory concentrations of antibiotics on Staphylococcus aureus interactions with fibronectin.
Bacterial adherence to host tissues relies on interactions between tissue macromolecules and bacterial surface molecules. One of the major predisposing factors to infection with Staphylococcus aureus is trauma to tissues. A common element in traumatized tissues is fibronectin. In previous studies, we have shown that fibronectin binds to Staph. aureus. In this paper, we have investigated the effects of subinhibitory concentrations of antibiotics on fibronectin interactions with Staph. aureus. Exposure of Staph. aureus to 1/4 MIC of penicillin increases the number of binding sites and enhances adherence of Staph. aureus to a collagen-fibronectin matrix. Chloramphenicol, erythromycin, clindamycin, and U57,930E all decreased the number of binding sites. Also, U57,930E reduced Staph. aureus adherence to a collagen-fibronectin matrix. Taken together, these data suggest that penicillin may enhance Staph. aureus adherence to tissue fibronectin whereas U57,930E might reduce such binding.
Anti-Bacterial Agents↗
Periprosthetic candidal infections following arthroplasty.
Candidal infection after prosthetic arthroplasty has been reported in six previous cases, to which four cases are now added. Candida albicans was the offending organism in four patients, Candida parapsilosis in three, Candida tropicalis in two, and Candida (Torulopsis) glabrata in one. None of the 10 patients had evidence of disseminated candidiasis, and, except for the uniform presence of a prosthesis, other underlying factors that are generally associated with candidal infections were present in only three. Clinical features that distinguished periprosthetic from natural bone and joint infection included an older patient population, the usual lack of predisposing factors other than the prosthesis, and the absence of evidence of disseminated candidiasis. All patients were treated with removal of the prosthesis and antifungal therapy, consisting of amphotericin B alone (six patients) or combined with 5-fluorocytosine (three patients) or ketoconazole (one patient). Infection appeared to be cured in nine of the 10 patients, but the follow-up was less than 1 year in five cases. Replacement with a new prosthetic joint was attempted in only two cases and successful in only one. Direct inoculation of organisms during surgery or transient unrecognized candidemia may initiate periprosthetic infection, which might then be promoted by favorable local factors, both mechanical and molecular. The role of prosthetic materials, candidal adhesins, and human factors such as fibronectin in initiating these infections has yet to be characterized.
Adult↗
Polymicrobial bacteremia: clinical and microbiologic patterns.
Between 1971 and 1987, 97 patients with polymicrobial bacteremia (PMB) were seen by a consulting infectious disease service. Seventy-four had severe underlying illnesses, and infection was hospital acquired in 80. PMB resulted from intraabdominal, urinary tract, or soft tissue infection in 45 patients, but a wide range of sources were implicated in the rest. Eleven patients had more than one source for the bacteremia, and, despite intensive diagnostic efforts, 24 had no identifiable source for at least one blood isolate. Bacteremia due to gram-negative bacilli most commonly occurred in intraabdominal, urinary tract, and wound infections; Escherichia coli and Klebsiella species were most frequently isolated. Streptococcus faecalis and Staphylococcus aureus were the predominant gram-positive isolates. Certain bacterial combinations seemed to provide a clue for predicting the source of PMB: for example, S. aureus together with gram-negative facultative rods usually arose from a skin or soft tissue source, whereas S. faecalis together with a gram-negative bacillus could often be traced to an intraabdominal infection. No unique clinical features appeared to predict the occurrence of bacteremia due to multiple rather than to a single organism. The mortality in patients was 21%, lower than has previously been described in PMB but similar to that reported for bacteremia due to a single organism.
Cross Infection↗
Spontaneous, nontraumatic gangrene due to Clostridium septicum.
Clostridium septicum is a major cause of spontaneous, nontraumatic gas gangrene. Unlike Clostridium perfringens, C. septicum is relatively aerotolerant and thus appears to be more capable of initiating infection in the absence of obvious damage to tissues. Six cases illustrate the clinical setting and fulminant nature of spontaneous gangrene caused by C. septicum. A lesion in the colon such as carcinoma is often present and is presumed to serve as a portal of entry to the bloodstream. Diabetes and leukopenia are also common predisposing conditions; compromise of vital host responses may facilitate proliferation of those organisms that settle out in the tissues. Acute lymphoma or leukemia during a course of chemotherapy is accompanied by damage to bowel mucosa and granulocytopenia, thus predisposing to spontaneous clostridial gangrene. Infection progresses in a fulminating manner; the majority of patients die within 24 hours of onset. Characteristic symptoms and signs include excruciating pain (although a sense of heaviness may be the only early symptom), swelling of tissues, crepitance, and bulla formation. A hallmark of C. septicum infection is the absence of acute inflammatory cells in involved tissues or in bulla fluid. A series of laboratory investigations demonstrated that fluid obtained from a bulla adversely affected the viability, morphology, and function of polymorphonuclear leukocytes (PMNs), which may explain the paucity of PMNs in involved tissues and may in part contribute to the fulminant progression observed in infection due to this organism.
Adenocarcinoma↗
Role of fibronectin in infective endocarditis.
It is now generally accepted that adherence of microorganisms to various components of cardiac valve surfaces is an important early event in the pathogenesis of infective endocarditis. Several lines of evidence suggest that fibronectin may have a role in this adherence process. Fibronectin is an important component of the extracellular matrix of endothelium and fibroblasts and is exposed when these tissues are injured. Fibronectin binds to platelets and fibrin and thereby contributes to the thrombogenicity of surfaces. Because the structure of fibronectin consists of multiple functional domains, fibronectin can bind simultaneously and specifically to microorganisms and various tissue elements such as collagen and cells and may facilitate the uptake of microorganisms by endothelial cells and fibroblasts. Subinhibitory concentrations of certain antibiotics interfere with the expression of bacterial fibronectin receptors and inhibit the binding of Staphylococcus aureus to collagen matrices; this interaction may have implications for antibiotic prophylaxis of infective endocarditis.
Endocarditis↗
Trends in bacteremic infection due to Streptococcus pyogenes (group A streptococcus), 1986-1995.
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Bacteremia↗