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Biomedical subjects

T Butler

Publications and source records attributed to T Butler.

At least 109 records · Page 6Linked to original sources

Interaction of Borrelia spirochetes with human mononuclear leukocytes causes production of leukocytic pyrogen and thromboplastin.

Relapsing fever caused by Borrelia spirochetes is characterized by episodes of spirochetemia, fever, and DIC. We examined the ability of Borrelia hermsii to induce production of leukocytic pyrogen and thromboplastin from human blood leukocytes in vitro. Organisms were found devoid of endotoxin by the Limulus assay. Human peripheral blood leukocytes were separated into MNC and PMN fractions and were incubated with two to five spirochetes per cell in 10% human serum. Supernatant fluids from MNC-spirochete mixtures produced mean increases in the temperature of rabbits of 0.80 degree to 1.35 degrees C, which were significantly higher than those caused by supernatant fluids of MNC or spirochetes alone (p less than 0.05). MNC-spirochete mixtures possessed seven to 15 times the thromboplastic activity of MNC suspensions alone, assayed with a modified one-stage prothrombin time. Supernatant fluids of PMNs and spirochetes, on the other hand, did not contain leukocytic pyrogen, and PMN suspensions did not produce thromboplastin. Cycloheximide (10 micrograms/ml), and inhibitor of protein synthesis, completely suppressed both pyrogen and thromboplastin production. Although intracellular spirochetes were observed within phagosomes of blood monocytes by electron microscopy, the production of leukocytic pyrogen and thromboplastin was not significantly altered by serum opsonins or by the inhibitors of phagocytosis cytochalasin B (5 micrograms/ml) or phenylbutazone (2 mg/ml). These results showed that Borrelia spirochetes stimulated human MNCs to produce increased amounts of leukocytic pyrogen and thromboplastin and that this stimulation required de novo synthesis of protein, was not mediated by endotoxin, and was not prevented by omitting opsonic proteins or by inhibiting phagocytosis.

Borrelia

Treatment of experimental Salmonella typhimurium infection with mecillinam and ampicillin.

The activities of mecillinam and ampicillin, alone and in combination, were evaluated in mice infected with the LT-2 strain of Salmonella typhimurium. The minimal inhibitory concentrations of mecillinam and ampicillin for this strain were, respectively, 6.2 and 0.4 microgram/ml of culture medium. In vitro synergy was demonstrated. CF-1 mice inoculated intraperitoneally with 10(4) colony-forming units of the LT-2 strain were used in the therapeutic assessments. Treatment of subgroups with graded doses of the respective penicillins or their combination was initiated 24 h after inoculation and repeated at 6-h intervals for 5 consecutive days. Animals were observed during 21 days for mortality or sacrificed for quantitative cultures of spleen homogenates at the end of the treatment. Ampicillin in doses of greater than or equal to 0.03 mg and mecillinam in doses of greater than or equal to mg reduced mortality rates from 77% in the saline-treated controls to a range of 0 to 4% (P less than 0.05). The same doses of antibiotics also extended the median times to death and lowered significantly the means of splenic bacterial counts. When both drugs were combined in doses that were partially effective or subinhibitory alone, no synergistic effects were observed. These results showed that mecillinam and ampicillin given alone were effective in treating S. typhimurium infection but that combinations of the two drugs were not synergistic in controlling the course of infections.

Amdinocillin

Plague in Brazil during two years of bacteriological and serological surveillance.

In north-east Brazil, where plague infection is endemic, bacteriological and serological methods were employed during a two-year period to determine accurately the occurrence of human infection and to define certain epidemiological features of both human and rodent infection. There were 67 confirmed cases of plague, predominantly among males and children. Most of these cases occurred in two inland rural plateaux of Ceara State. Clustering of cases in place and time was common, as was a history of contact with rats. Peak occurrence was in November 1978, during the warm, harvest time of year. Rodent surveillance resulted in isolation of Yersinia pestis from 33 animals, most of them from the field rodent, Zygodontomys pixuna, in the States of Pernambuco and Ceara. Our results indicate a decline in the number of human cases from previous years but show that several foci remain active and that serological testing, in addition to routine bacteriological testing, can assist workers in maintaining the surveillance of both human and rodent plague in Brazil.

Adolescent

Phagocytosis of Borrelia recurrentis by blood polymorphonuclear leukocytes is enhanced by antibiotic treatment.

The removal of Borrelia spirochetes from the blood in relapsing fever was studied by examining patients' blood phagocytic cells with the Dieterle silver stain. Polymorphonuclear leukocytes ingested Borrelia at increased rates for several hours after antibiotic treatment, during which time the total numbers of circulating plasma spirochetes were decreasing. Incubation of infected blood at 37 degrees C for 2 h resulted in a progressive increase in phagocytosis. Addition of penicillin G and tetracycline to infected blood caused a further enhancement of phagocytosis. Electron microscopy of polymorphonuclear leukocytes revealed spirochetes in phagosomes. These results indicated that blood polymorphonuclear leukocytes have a prominent role in removing Borrelia from the plasma and suggested that antibiotics act by altering the surface of spirochetes to render them more susceptible to phagocytosis.

Adult

Septicemia caused by Capnocytophaga in a granulocytopenic patient with glossitis.

A patient receiving immunosuppressive treatment for multiple myeloma became granulocytopenic, and acute glossitis developed. Blood cultures were positive for Capnocytophaga, a fastidious Gram-negative bacillus that is known to be part of the normal oral flora and a pathogen for periodontitis. The infection responded to treatment with antibiotics, including penicillin G, to which the organism was sensitive. This is one of the first reports of Capnocytophaga septicemia, and suggests that this organism may be an important pathogen in immunosuppressed patients with oral mucosal lesions.

Acute Disease

Effect of a Salmonella group H1 R factor on virulence and response of infections to antimicrobial therapy.

A group H1 R factor encoding resistance to chloramphenicol, streptomycin, sulfonamide, and tetracycline was transferred into Salmonella typhimurium LT-2. The virulence of LT-2 for mice, as assessed by intraperitoneal 50% lethal dose and the number of organisms in the spleen, was not affected by the R factor. On the other hand, the R factor conferred resistance in mouse infections to therapy with chloramphenicol and trimethoprim plus sulfamethoxazole.

Animals

Experimental Eikenella corrodens endocarditis in rabbits.

The ability of Eikenella corrodens to cause endocarditis in catheterized rabbits was studied. E. corrodens 1073, the serum-resistant strain used in the study, was isolated from a human periodontitis lesion. Thirty-four rabbits, surgically catheterized across the aortic valve and injected intravenously 24 to 48 h later with 10(7) to 10(9) log-phase organisms, were studied. Only three rabbits developed positive blood cultures and only two rabbits died before the time of sacrifice at 14 days after infection. Autopsies showed that all rabbits developed aortic vegetations, 52% of which were culture positive for E. corrodens. The organisms were recovered from aortic vegetations in a mean concentration of 10(5.3) colony-forming units/g of tissue and from liver or kidney in 28% of the animals in concentrations from 10(2) to 10(4) colony-forming units/g. Indirect immunofluorescent staining of vegetations, with the use of specific rat antiserum to E. corrodens 1073 and fluorescein isothiocyanate-labeled goat antirat serum, revealed colonies of E. corrodens in culture-negative vegetations as well as in those which were culture positive. The results showed that E. corrodens was an effective pathogen in the rabbit model of endocarditis, in which the disease was infrequently bacteremic and rarely fatal.

Agglutinins

Typhoid fever. Studies of blood coagulation, bacteremia, and endotoxemia.

Patients with typhoid fever were studied to determine whether disseminated intravascular coagulation (DIC), circulating bacteria, and endotoxemia were responsible for the signs and symptoms of their illnesses. Coagulation tests in 28 patients detected thrombocytopenia in 17, hypofibrinogenemia in nine, and elevated titers of fibrinogen-related antigens in 20. Repeated testing during convalescence showed a return toward normal values. Intestinal bleeding, however, did not correlate with abnormalities of coagulation tests. Thus, DIC occurred commonly but appeared to be a subclinical event in these patients. In 25 patients with positive blood cultures for Salmonella typhi, quantitative cultures detected from less than 10 to 9 x 10(2) bacteria/ml. Limulus tests for endotoxin in plasma were negative in all 21 patients tested. These results indicated that the concentrations of circulating bacteria and endotoxin in typhoid fever are lower than in other Gram-negative bacterial infections and suggested that circulating bacteria and endotoxin do not play a major role in the pathogenesis of typhoid fever.

Antigens

Activation of protein mediators of inflammation and evidence for endotoxemia in Borrelia recurrentis infection.

Fifteen patients with Borrelia recurrentis infection were studied to evaluate the role of certain plasma proteins and endotoxin in the pathophysiology of both the acute illness and the Jarisch-Herxheimer-like reaction. The causative spirochetes disappeared from the blood during the Jarisch-Herxheimer-like reaction, which occurred about 2 hours after antibiotic therapy. The mean titers of Hageman factor, plasma prekallikrein and serum hemolytic complement activity were decreased at the time of admission and 2 hours after treatment, and rose to normal values during convalescence. Serum properdin titers were decreased in 14 patients at the time of admission, in 12 patients 2 hours after treatment, and in none during convalescence. The frequency of elevated levels of fibrinogen-related antigens increased from three patients at the time of admission to 12 patients 2 hours after treatment. Results of plasma limulus tests for endotoxin-like material were positive in 11 patients at the time of admission and in 13 patients 2 hours after treatment. These findings demonstrated that Hageman factor, prekallikrein and proteins of the complement system are activated in B. recurrentis infection and that endotoxin may play a role in both the acute illness and in the development of the Jarisch-Herxheimer-like reaction after treatment.

Adolescent