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Biomedical subjects

R C Fader

Publications and source records attributed to R C Fader.

At least 19 recordsLinked to original sources
PubMed2000

In vitro activity of minocycline against respiratory pathogens from patients with cystic fibrosis.

Our objective was to determine the in vitro activity of minocycline against isolates of Burkholderia cepacia (BC), Stenotrophomonas maltophilia (SM), and Pseudomonas aeruginosa (PA) cultured from the respiratory tract of patients with cystic fibrosis (CF). Cultures of BC, SM, and PA were isolated in a hospital bacteriology laboratory from the sputum or oropharyngeal cultures obtained from patients attending a Cystic Fibrosis Center, and were prospectively tested for in vitro sensitivity to minocycline by Kirby-Bauer disk diffusion. From January 1994 to July 1995, 116 cultures from 61 patients had at least one of the three pathogens; 9/61 (15%) patients had an isolate of BC, and 7/9 (78%) had an initial isolate sensitive to minocycline, of which 3 were sensitive only to minocycline; 2 cultures were resistant to all antibiotics. Four of 7 patients with BC were treated with minocycline; 3 patients developed resistant isolates 3-13 months after therapy. Five of 61 patients (8%) had an isolate of SM: 4/5 (80%) of these isolates were sensitive to minocycline, of which 1 was sensitive only to minocycline. Fifty-five of 61 patients (90%) had at least one PA isolate, with 112 morphotypes recovered from 90 cultures: 40/112 morphotypes (36%) were sensitive to minocycline, 65 (58%) were resistant, and 7 (6%) were intermediate in sensitivity. We conclude that the marked in vitro activity of minocycline against BC and SM isolated from patients with CF suggests that minocycline may have an adjunct role in the antimicrobial therapy of multidrug resistant, respiratory pathogens in CF.

Adolescent↗
PubMed1994

The effect of anti-exotoxin A on the adherence of Pseudomonas aeruginosa to hamster tracheal epithelial cells in vitro.

One of the most important initial events of colonization and infection of epithelial tissues is the adherence of bacteria to mucosal surfaces. Bacterial adhesion to the epithelial cell may be mediated by a variety of adhesins, including exoproducts. One of these exoproducts, exotoxin A (EA) is a three-domain bacterial toxin that kills mammalian cells by gaining entry to the cytosol and inactivating protein synthesis. In the present study, HTE cultures, 2-4 weeks in vitro (containing both ciliated and non-ciliated cells), were treated for 1 hr with two different non-mucoid strains of Pseudomonas aeruginosa (1 x 10(8) organisms/ml) in the presence of anti-EA. 50 randomly selected fields were evaluated via SEM at x2500 magnification and the number of bacterial clusters/field quantitated. The results of this study indicate, first, that both piliated (ATCC15692) and non-piliated (PAKp) P. aeruginosa will bind to the HTE cells and, second, that treatment of HTE cells with either strain of P. aeruginosa in the presence of anti-EA will reduce bacterial binding by 25% to 50%. Thus, EA may participate in the adhesion of P. aeruginosa to respiratory tract epithelia.

ADP Ribose Transferases↗
PubMed1993

Exaggerated cardiopulmonary response after bacteremia in sheep with week-old thermal injury.

OBJECTIVE: To determine if thermal injury impairs pulmonary intravascular clearance of bacteria and therefore leads to exaggerated cardiopulmonary dysfunction in sheep, since endotoxin infusion has been previously shown to induce more severe pulmonary injury after thermal injury. DESIGN: Prospective, unblinded, randomized, controlled trial. SETTING: Laboratory at a large university medical center. INTERVENTIONS: Chronically instrumented, anesthetized sheep received a 40% total body surface area, third-degree thermal injury. Live Pseudomonas aeruginosa (10(7) P. aeruginosa/min for 1 hr; n = 6) were infused 7 to 10 days after thermal injury. Similarly prepared noninjured sheep received the same pseudomonas infusion (n = 7) or saline (n = 7). MEASUREMENTS AND MAIN RESULTS: Bacterial clearance, which measures phagocytosis by the pulmonary intravascular macrophages, was equally efficient in intact sheep and sheep with thermal injury. Pulmonary hypertension persisted for 18 hrs after thermal injury, compared with 8 hrs in noninjured sheep. Lung lymph flow significantly increased from 6 to 8 hrs in only the thermal injury group. Both bacteremic groups developed a hyperdynamic circulation from 6 to 8 hrs, but cardiac index was 1 to 1.5 L/min/m2 higher in thermally injured sheep. Total peripheral resistance index decreased significantly from 6 to 24 hrs in thermally injured sheep and from 6 to 12 hrs in intact bacteremic sheep. Mean arterial pressure of thermally injured sheep was increased at baseline and for the first 6 hrs compared with noninjured animals. Mean arterial pressure decreased from 6 to 24 hrs in sheep with thermal injury but did not change in intact bacteremic sheep. CONCLUSIONS: Bacterial clearance was not impaired by preceding thermal injury in sheep. Bacteremia in the presence of a preexisting thermal injury led to more persistent pulmonary hypertension and an exaggerated hyperdynamic circulation.

Animals↗
PubMed1989

Cardiopulmonary changes occurring with pulmonary intravascular clearance of live bacteria in sheep.

Sheep were infused with live bacteria to determine if the bacteria are phagocytized in the pulmonary circulation and to study the associated cardiopulmonary changes. Unanesthetized animals (n = 9) with chronic hemodynamic and pulmonary lymph catheters received a 1 hr central venous infusion of live Pseudomonas aeruginosa (5 x 10(7) Ps./minute) and were compared to a sham group (n = 7). The pulmonary arterial levels of bacteria were five to 100 times higher than the aortic levels. Pulmonary intravascular clearance rates were 79-91%. Electron microscopy of the lungs 24 hr after the bacterial infusion showed that pulmonary intravascular macrophages and neutrophils phagocytosed the bacteria. Severe initial and mild persistent pulmonary hypertension occurred. The pulmonary lymph flow was elevated, initially from hydrostatic pressure and later from increased permeability. A hyperdynamic circulation occurred from 6 to 18 hr, with elevated cardiac index and lowered systemic vascular resistance and mean arterial pressure, mimicking cardiopulmonary changes seen in clinical sepsis. The removal of bacteria in the lungs may contribute to the injury in sheep.

Animals↗
PubMed1988

Evidence that in vitro adherence of Klebsiella pneumoniae to ciliated hamster tracheal cells is mediated by type 1 fimbriae.

Clinical isolates of fimbriated and nonfimbriated Klebsiella pneumoniae were examined for the ability to adhere to hamster tracheal cells cultured in vitro. Fimbriated-phase K. pneumoniae adhered preferentially to ciliated cells, whereas nonfimbriated-phase organisms were not adherent. The adherence was inhibited by D-mannose but not D-glucose, suggesting that type 1 fimbriae serve as the adhesin in the attachment process.

Animals↗
PubMed1988

Evaluation of 9-chloro-9-[4-(diethylamino)phenyl]- 9,10-dihydro-10-phenylacridine hydrochloride (C-390) in broth and agar media for identification of Pseudomonas aeruginosa.

Brain heart infusion broth and Mueller-Hinton agar containing the compound 9-chloro-9-[4-(diethylamino)phenyl]- 9,10-dihydro-10-phenylacridine hydrochloride (C-390) were evaluated as selective media for identifying Pseudomonas aeruginosa. Of the 192 Pseudomonas spp. and 68 additional oxidase-positive or glucose-nonfermenting gram-negative organisms tested, only P. aeruginosa (120 of 121 isolates) and certain strains of Pseudomonas cepacia, Aeromonas hydrophila, and Achromobacter xylosoxidans were able to grow in brain heart infusion broth containing 15 micrograms of C-390 per ml. When production of green or yellow-green pigment after overnight growth on Mueller-Hinton agar containing 30 micrograms of C-390 per ml was used as the criterion for identification, only P. aeruginosa produced a positive test (96% sensitivity and 100% specificity). The agar medium, therefore, can provide a single differential medium for the overnight identification of P. aeruginosa.

Acridines↗
PubMed1988

Infections caused by dematiaceous fungi: chromoblastomycosis and phaeohyphomycosis.

Because of the increased incidence of infections caused by dematiaceous fungi, it is important to clearly define the conceptual basis for the clinical nomenclature for infections caused by these fungi. When considering dematiaceous fungal infections, there is a continuum of diseases that can be separated into the three categories of chromoblastomycosis, phaeohyphomycosis, and mycetoma. The diseases chromoblastomycosis and phaeohyphomycosis are compared and contrasted in this chapter.

Chromoblastomycosis↗
PubMed1988

Mycetoma: a contemporary concept.

Mycetoma is a localized noncontagious infection that involves cutaneous and subcutaneous tissue, fascia, and bone. The disease is caused by either aerobic actinomycetes or fungi that are normally associated with soil and plant material. In the past, actinomycosis, botryomycosis, fungus balls, and some forms of Majocchi's granuloma trichophyticum have been confused with mycetoma. Antimicrobic chemotherapy and surgery are management approaches used to resolve this disease.

Bacterial Infections↗
PubMed1987

Evaluation of topical therapy with silver-kaolin (Argostop) in an experimental model of burn wound sepsis.

Burn wound therapy with silver-kaolin, a topical agent applied as an aerosol spray, was evaluated in male rats given a 20 per cent total body surface area, full thickness dorsal scald burn. Burn wounds treated with silver-kaolin healed at rates comparable to untreated wounds. No significant differences were noted in the numbers or types of organisms colonizing the wounds of treated and untreated rats at 5, 12 and 19 days post-burn. To evaluate the effectiveness of silver-kaolin in treating burn wound sepsis, rats were inoculated on the wound surface with 2.5 x 10(8) Pseudomonas aeruginosa. This inoculum resulted in 100 per cent mortality in untreated rats. Rats treated with silver-kaolin had a mortality rate of 71 per cent, compared to a 9 per cent mortality rate in rats treated with 1 per cent silver sulphadiazine. When silver-kaolin was applied to the wound prior to bacterial inoculation, the mortality rate was reduced to 6 per cent. When wounds were treated with kaolin alone and then inoculated with bacteria, the mortality rate was 50 per cent, indicating that part of the effectiveness of silver-kaolin appeared to be due to a barrier effect. These results indicate that silver-kaolin may be useful for preventive topical antimicrobial therapy of acute burns or after wound debridement or excision, but is not suitable for therapy of wounds previously colonized by microorganisms.

Administration, Topical↗
PubMed1987

Staphylococcal toxins: screening of burn wound isolates and evidence for alpha-haemolysin production in the burn wound.

Culture filtrates of Staphylococcus aureus strains isolated from burn patients were examined for cytotoxic activities. A large molecular weight cytotoxin (MW = 253,000 daltons) that exhibited cytotoxicity for human foreskin cells and haemolytic activity against human and rabbit erythrocytes was identified. The cytotoxic activity could be completely neutralized by antiserum formed against the cytotoxin. Further characterization of the molecule by isoelectric focusing revealed that the cytotoxin was composed of at least two toxic factors of smaller molecular weight. Both factors exhibited cytotoxicity to tissue-culture cells; however, one factor lysed rabbit but not human erythrocytes whereas the other factor had the opposite haemolytic pattern. The cytotoxicity of each factor was neutralized by the antiserum formed against the cytotoxin. A cytotoxic factor that exhibited haemolytic activity for rabbit erythrocytes, and that was neutralized by the cytotoxin antiserum, was identified in burn wound extracts of mice infected with Staph. aureus. On the basis of molecular weight and isoelectric focusing data, we conclude that the large molecular weight cytotoxin was composed of an aggregation of alpha-haemolysin and another presently unidentified toxic molecule, possibly delta-toxin. Alpha-haemolysin appears to be produced in vivo during experimental staphylococcal burn wound infection.

Animals↗
PubMed1986

Evolution of lymph thrombi in experimental Brugia malayi infections: a scanning electron microscopic study.

Lymph thrombi in cats experimentally-infected with Brugia malayi were examined by scanning electron microscopy. A variety of morphological forms were noted and it appeared that thrombi undergo a maturation process characterized by at least three transitional phases. Initially, the thrombus consists of erythrocytes encased in fibrin (Phase I). Phase II thrombi are characterized by the appearance of phagocytic cells and fibroblasts on the surface of the thrombus. At the end of the maturation process, the thrombus surface consists solely of fibroblasts or endothelial cells, perhaps derived from the vessel wall (Phase III). Occlusion of the lymphatic lumen by thrombi and the accompanying inflammatory response triggered by B. malayi infection may be a major factor in the pathogenesis of lymph stasis in this disorder.

Animals↗
PubMed1985

Chemical parameters, antimicrobial activities, and tissue toxicity of 0.1 and 0.5% sodium hypochlorite solutions.

ffe chemical parameters, antimicrobial activity, and tissue toxicity of two sodium hypochlorite (NaOCl) solutions buffered to a physiologic pH were studied. Initially, a 0.5% NaOCl solution buffered with 3 g of NaH2PO4 per liter was examined. The solution had a pH of 7.49 and an osmolality of 352 mOsmol/liter. When compared with unbuffered and NaHCO3-buffered 0.5% NaOCl solutions, the NaH2PO4-buffered solution was significantly more effective in killing Staphylococcus aureus in vitro. However, the pH of the NaH2PO4-buffered solution decreased over time with a concomitant decrease in antibacterial activity. A freshly prepared solution decontaminated human cadaveric skin colonized by S. aureus, Pseudomonas aeruginosa, or Candida albicans in vitro within 10 min of exposure, whereas a 24-h-old solution cleared the skin of organisms within 15 min. When gauze soaked with 0.5% NaOCl was applied to guinea pig skin for 2 weeks, a 15% decrease in basal cell viabilities was noted. Because of the pH instability and basal cell toxicity, a 0.1% NaOCl solution buffered with NaH2PO4-Na2HPO4 was evaluated. This solution had an osmolality of 386 mOsmol/liter and a pH of 7.4 that was stable over 1 week. A freshly prepared 0.1% NaOCl solution decontaminated skin colonized with S. aureus, C. albicans, and P. aeruginosa within 10, 20, and 30 min, respectively. A 24-h-old solution did not completely decontaminate the colonized skin but significantly reduced the number of microorganisms on the skin surface (P less than 0.001). Application of this solution of guinea pig skin for 2 weeks produced no significant effect on basal cell viabilities. These solutions may serve as alternative topical agents for use in burn therapy.

Animals↗
PubMed1985

Experimental candidiasis after thermal injury.

The ability of Candida albicans to infect thermally injured mice was studied. Female mice were either left unburned or given a 20% total body surface area 2-s or 7-s scald burn. The wound or skin surface was then inoculated with a human burn wound isolate of C. albicans. At 4 h postburn, approximately 10(2) to 10(3) CFU/g of tissue could be recovered from the skin of burned and unburned animals. Unburned mice cleared the organisms from the skin by 72 h, whereas in 7-s-burned animals, the candida increased in numbers to approximately 10(7) CFU/g of tissue. The ability of the organisms to invade systemically after wound surface inoculation was examined in mice given either a 2-s or a 7-s scald burn. Each injury was histologically confirmed as a full-thickness (third degree) burn, with slightly deeper tissue damage observed with the 7-s burn. At each time period examined (1, 4, 7, and 10 days), there were significantly fewer organisms in the wounds of mice given the 2-s injury than in wounds of mice burned for 7 s (P less than 0.05). In 3 of 33 mice given a 7-s injury, organisms were recovered from the kidneys at the time of sacrifice, whereas no evidence of invasion into the kidneys was noted in mice given a 2-s thermal injury. This study demonstrated that thermal injury enhances the ability of C. albicans to infect mice and that the depth of burn appears to be an important factor in determining whether the organisms can invade the burn wound to cause systemic infection. This animal model should be valuable in elucidating the virulence factors of C. albicans that play a role in the pathogenesis of candidiasis after thermal injury.

Animals↗
PubMed1983

Elevated cAMP in intestinal epithelial cells during experimental cholera and salmonellosis.

Cholera and salmonellosis are two diarrheal diseases in which intestinal tissue cyclic adenosine monophosphate (cAMP) concentrations are elevated. Investigations of each experimental disease were initiated to identify the specific intestinal cells containing the elevated cAMP. Epithelial cells were eluted from the mucosa of infected and control intestinal loops of adult rabbits, after which the cAMP content of the epithelial cell fractions and the lamina propria cells was extracted and assayed. The identity of the epithelial cells (in the villus tip-to-crypt cell gradient) was monitored by measuring their intracellular alkaline phosphatase activity, while scanning electron microscopy was used to visualize the effects of infection and cell elution techniques. Clearly, in both experimental cholera and salmonellosis, elevated cAMP levels were associated with crypt epithelial cells. Villus tip epithelial cells from either infection tended to contain less cAMP than those of noninfected control tissue. In Salmonella-infected loops, it was apparent that cAMP was also elevated in lamina propria cell fractions. Lamina propria cells from V. cholerae-infected intestinal loops contained only basal levels of cAMP. In vitro exposure of isolated intestinal cells from normal rabbit intestine to a cell-free lysate of Salmonella resulted in elevation of cAMP in the epithelial cells and lamina propria cells. We conclude that in experimental cholera and salmonellosis, significant elevation of the cAMP levels occurred in intestinal crypt cells, consistent with an enterotoxin-mediated mechanism. In Salmonella-infected loops, it was unclear if the increased concentration of cAMP in lamina propria cells was generated by enterotoxin released from the invasive salmonellae or by prostaglandins formed during the inflammatory response to the bacteria, or by both mechanisms.

Alkaline Phosphatase↗
PubMed1983

Sodium hypochlorite decontamination of split-thickness cadaveric skin infected with bacteria and yeast with subsequent isolation and growth of basal cells to confluency in tissue culture.

The ability of sodium hypochlorite to decontaminate skin while leaving sufficient epidermal cell viability for growth in tissue culture was investigated with an in vitro system. Split-thickness cadaveric skin was infected with Staphylococcus aureus, Pseudomonas aeruginosa, and Candida albicans and subsequently treated with various concentrations of sodium hypochlorite for various time intervals. Exposure to a 0.5% solution of sodium hypochlorite for 6 min effectively decontaminated the skin while leaving 66% of the basal cells viable. The basal cells were subsequently grown to confluency in tissue culture. This study demonstrates that microbial colonization of skin can be eliminated by exposure to dilute hypochlorite. This procedure, while decontaminating the skin, leaves sufficient viability of epidermal cells for subsequent growth and expansion in tissue culture, elements essential for grafting over wounds.

Bacteria↗
PubMed1982

Purification and chemical characterization of type 1 pili isolated from Klebsiella pneumoniae.

Type 1 pili were purified from a Klebsiella pneumoniae strain isolated from a human urinary tract infection. The pili were removed from the bacteria by mechanical shearing, precipitated out of solution by ammonium sulfate, solubilized in a deoxycholate-containing buffer, and finally purified by gel filtration. Chemical characterization of the isolated pili revealed a single protein subunit (pilin) which had a Mr = 21,500. Amino acid compositional analysis revealed a high content of residues that contribute significantly to secondary structure. Automated sequence analysis of the NH2-terminal region revealed a striking homology (79% identity) with type 1 pili of Escherichia coli. In contrast, NH2-terminal sequence comparison of K. pneumoniae pilin with other previously reported bacterial pilins showed no significant homology. No immunological cross-reactivity was detectable between E. coli and K. pneumoniae pili when tested by Ouchterlony double immunodiffusion or by rocket immunoelectrophoresis. The results of this study, when compared to other studies of bacterial pili, indicate that type 1 pili from members of the Enterobacteriaceae share morphological similarities and that their monomeric subunits are chemically similar. In addition, these results give strong evidence that the type 1 pilins of the enteric bacteria represent a separate class of homologous pilins.

Amino Acid Sequence↗
PubMed1982

Klebsiella pneumoniae-induced experimental pyelitis: the effect of piliation on infectivity.

The effect of bacterial piliation on the infectivity of Klebsiella pneumoniae in the renal pelvis was examined by means of piliated and nonpiliated variants derived from a single parent strain. Piliated-phase variants were significantly more infective as determined by viable counts of bacteria isolated from the kidneys at the time of sacrifice. In addition, scanning electron microscope was used to examine the renal pelvis for evidence of infection. Kidneys infected with piliated-phase organisms exhibited greater tissue damage -- both in the magnitude of tissue alterations observed and in the number of kidneys affected. Thus, it is concluded that piliation contributes to the ability of K. pneumoniae to infect the renal pelvis following reflux from the bladder.

Animals↗