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Biomedical subjects

J S Walker

Publications and source records attributed to J S Walker.

At least 109 records · Page 6Linked to original sources
PubMed1978

Continuous monitoring of mixed venous oxygen tension (PvO2) in cardiorespiratory disorders.

The development of a miniature polarographic electrode mounted in the tip of a double-lumen plastic catheter has made possible continuous in-vivo monitoring of oxygen tension. Inexpensive catheters of this type have already proved of value as a means of continuously monitoring arterial oxygen tension in the newborn. In 25 patients with acute respiratory failure we found that these catheters could be safely and easily flow-guided into the pulmonary artery. In this way continuous recordings of mixed venous oxygen tension (PvO2) could be made for a period of several days. In our experience a sustained fall of PvO2 below 40 mm Hg proved to be a reliable indicator of respiratory or cardiac deterioration not always obvious by observation. In the patients described, falls of this order were seen after reductions in inspired oxygen concentration, in acute respiratory failure, in accidental underventilation, and in hypovolaemia and cardiac arrythmias. In some very ill patients routine nursing care involving movement of the patient caused pronounced falls of PvO2. Although electrode drift was an occasional problem, this could be checked by intermittent blood-sampling and recalibration if necessary.

Aged↗
PubMed1977

Aerosol therapy of influenza infections of mice and primates with rimantadine, ribavirin, and related compounds.

Ribavirin administered as small-article aerosols had significant therapeutic effect in the treatment of viral respiratory infections induced by influenza virus. The preliminary experiment using ribavirin to treat influenza infection in the squirrel monkey is encouraging. We expect to extend these experiments by initiating therapy at a later time to investigate the potential value of ribavirin in a clinical situation. Several derivatives of ribavirin are effective antiviral compounds. The tri-O-acetyl derivative appears to offer a potential advantage over ribavirin, although this cannot be stated with certainty since the data were obtained from separate experiments. Radiolabeling has been used as a means of measuring tissue concentration and clearance rates of various drugs. It is hoped that the use of labeled ribavirin and the tri-O-acetyl derivative will assist us in determining whether a depot of antiviral drug is created in pulmonary tissues after administration as a small-particle aerosol. These experiments are now in progress.

Adamantane↗
PubMed1977

Scrub typhus infection in rats in four habitats in Peninsular Malaysia.

Rickettsia tsutsugamushi isolations were attempted from blood samples obtained from rats captured in four adjacent habitats near Kuala Lumpur, Malaysia. Antibody surveys were also made. Rickettsial infections were most frequent in rats captured in the forest and in lalang grass (Imperata cylindrica) and least frequent in the most extensively disturbed habitat, an Orang Asli (aborigine) village. Forest rats such as Rattus sabanus (31%), as well as rats in the subgenus R. (Rattus), i.e. R. tiomanicus (26%) and R. argentiventer (35%) had frequent active infections. The house rat R. exulans had less frequent infections (15%). Frequency of antibody occurrence followed a similar pattern. No marked seasonal differences in the frequency of infections could be detected during the 18-month study.

Animals↗
PubMed1977

Response of influenza virus-infected mice to selected doses of ribavirin administered intraperitoneally or by aerosol.

The effects of graded doses of ribavirin administered either by aerosol or intraperitoneally were compared in influenza virus-infected mice. The median effective dose values (based upon percent survival) were 3.3 and 15.8 mg/kg per day for the aerosol and intraperitoneal routes, respectively. Lung lesion scores and titer of virus were lower after aerosol than intraperitoneal therapy.

Aerosols↗
PubMed1977

Fat of Coxiella burnetti in macrophages from immune guinea pigs.

The interaction between Coxiella burnetii and peritoneal macrophages obtained from immune guinea pigs was studied by transmission electron microscopy. Phagocytosis and subsequent fate of ingested phase I and II rickettsiae were compared. Phase I rickettsiae were more resistant to phagocytosis than were phase II organisms. Macrophages from phase I- and II-immunized animals were equally capable of phagocytizing rickettsiae. Phase I and II rickettsiae previously treated with normal serum multiplied and destroyed macrophages from guinea pigs that had been immunized with phase II rickettsiae. Phase II organisms were initially suppressed in macrophages from phase I-immunized animals, but eventually multiplied in these cells. In contrast, only phase I organisms were destroyed by macrophages from phase I-immunized animals. Treatment of rickettsiae with immune serum enhanced ingestion by macrophages and potentiated the destruction of organisms by both types of macrophages. The macrophage migration inhibition assay was performed on peritoneal exudate cells from immune animals. Migration of peritoneal macrophages from phase I-immunized guinea pigs was inhibited, whereas macrophages from phase II-immunized animals migrated when cells were cultured in the presence of killed, intact phase I or II C. burnetii.

Antibodies, Bacterial↗
PubMed1977

Immunoprophylaxis of experimental Mycoplasma pneumoniae disease: effect of aerosol particle size and site of deposition of M. pneumoniae on the pattern of respiratory infection, disease, and immunity in hamsters.

The distribution of Mycoplasma pneumoniae infection in the respiratory tract and the extent of pulmonary pathology were determined by the site of deposition and the number of organisms administered to hamsters. Infection of the upper and lower areas of the respiratory tract occurred when organisms were introduced into both areas by small-particle aerosol (2.3 micrometer) or by intranasal (i.n.) instillation of a 200-microliter inoculum. In contrast, when organisms were delivered primarily to the upper respiratory tract by large-particle aerosol (8 micrometer) or by i.n. instillation of a small volume of inoculum (2 or 20 microliter), infection remained limited to this area in most or all instances. When the lungs became infected after i.n. administration of a 200-microliter inoculum, the most extensive pulmonary lesions were seen in the animals given the largest number of organisms. Each of the modes of administration of M. pneumoniae initiated an infection which conferred measurable resistance to a subsequent challenge capable of inducing extensive pulmonary disease. The most effective resistance was induced by the two modes of administration which produced an infection involving the entire respiratory tract, i.e., small-particle aerosol or i.n. instillation of a 200-microliter inoculum.

Administration, Intranasal↗
PubMed1977

Continuous aerosol therapy system using a modified Collison nebulizer.

A Collison nebulizer was incorporated into an exposure system for administering antiviral compounds as continuous aerosols to mice infected with influenza virus. The nebulizer was modified to control aerosol output by varying the liquid feed rate. A multiple regression equation was developed from data obtained with uranine dye to define the aerosol concentration of the dye in the system as a function of the concentration of the dye in the spray fluid and the rate at which it was aerosolized. The rate of change of the concentration of the test solution due to evaporative losses was also ascertained for a 1-ml/min feed rate over a 23.5-h period of operation. Procedures are outlined for using these relationships to determine the concentration of a given drug that will result in a given dose. Performance data for the drug ribavirin are presented.

Aerosols↗
PubMed1976

Small-particle aerosols of antiviral compounds in treatment of type A influenza pneumonia in mice.

Three chemotherapeutic drugs active against type A influenza virus (amantadine, rimantadine, and ribavirin) were tested as therapeutic agents against established infections with influenza virus in mice. The drugs were administered intraperitoneally or as aerosols either from 6 hr to four days or from three to seven days after infection. Small-particle aerosols were administered continuously 24 hr per day. Continuous dissemination of aerosols was superior to intraperitoneal administration, as evidenced by higher survival rates at 21 days. Rimantadine, amantadine, and ribavirin were effective when treatment was delayed for three days. Ribavirin was the most efficacious if therapy was initiated as an aerosol 6 hr after infection. In contrast to amantadine, ribavirin given in samll-particle aerosols at 6 hr prevented the development of pneumonia and decreased titers of virus in lung.

Administration, Intranasal↗
PubMed1976

Therapeutic effects of ribavirin given by the intraperitoneal or aerosol route against influenza virus infections in mice.

Ribavirin (1-beta-d-ribofuranosyl-1,2,4-triazole-3-carboxamide) is an effective antiviral agent against type A influenza infection of mice. Therapy was most effective when administered as a small-particle aerosol early in the infection. Treatment was also effective by either the intraperitoneal or aerosol route in mice with histological evidence of pneumonia. Ribavirin increased the percent survival, lowered lung virus titers, and decreased the development of lung pathology when therapy was initiated at 6 h as a small-particle aerosol. There was no evidence of pulmonary toxicity or immunosuppressive effects.

Aerosols↗
PubMed1976

Aerosol vaccination of mice with a live, temperature- sensitive recombinant influenza virus.

Mice were vaccinated intranasally (i.n.) or with small-particle aerosols (SPA; 2 mum) or large-particle aerosols (LPA; 8 mum) of an attenuated, temperature-sensitive, recombinant A influenza (H3N2) virus, ts-1 (E). Serum virus-neutralizing and hemagglutination inhibition antibodies were detected for all vaccinated mice by 28 days. Bronchoalveolar wash fluids had increased levels of immunoglobulin (IgG, IgA) only in the i.n. -vaccinated mice. Hemagglutination and virus-neutralizing antibodies were detected in the SPA- and i.n. -vaccinated groups but not in the LPA vaccinates. Upon challenge with SPA of a mouse virulent H3N2 influenza vitus, total protection was obtained for the SPA- and I.N. -vaccinated mice, whereas only 89% of the LPA group survived. Replication of the challenge virus was signifcantly repressed in both the lower and upper respiratory tracts of the three groups of vaccinated mice compared to the nonvaccinated controls. The protection afforded the SPA- and i.n. -vaccinated mice was the same as measured for mice after recovery from earlier subelthal active infection with virulent virus.

Aerosols↗
PubMed1976

Interaction between Coxiella burnetii and guinea pig peritoneal macrophages.

The phagocytosis and subsequent degradation of phase I and II Coxiella burnetii by macrophages obtained from immune and nonimmune guinea pigs were compared. Phase I rickettsiae were more resistant to phagocytosis than were phase II organisms. There was no significant difference in the percentage of phagocytosis of either phase of rickettsiae by macrophages from immune or nonimmune animals. After ingestion, phase I and II organisms pretreated with normal serum multiplied and destroyed normal macrophages as well as macrophages obtained from guinea pigs immunized with phase II rickettsiae. In contrast, only phase I organisms were degraded by macrophages from phase I-immunized animals in the presence of normal serum. Immune serum rendered rickettsiae more susceptible to phagocytosis and also potentiated the destruction of organisms by all types of macrophages. The specificity of macrophages from phase I animals to degrade only phase I rickettsiae was demonstrated by the ability of Rickettsia rickettsii to replicate in these macrophages.

Animals↗
PubMed1976

Electron microscopic study on the interaction between normal guinea pig peritoneal macrophages and Coxiella burnetii.

An electron microscopic study was conducted to explore the interaction between normal guinea pig peritoneal macrophages and phase I and II Coxeilla burnetii previously treated with either normal or immune serum. A comparison was made on the efficiency of phagocytosis and subsequent killing of rickettsiae by macrophages. Both phases of rickettsiae previously treated with normal serum multiplied within phagosomes after phagocytosis with resultant destruction of macrophages. In contrast, suspending rickettsiae in immune serum rendered them more susceptible to phagocytosis and potentiated their destruction within macrophages.

Animals↗
PubMed1975

Mammals and scrub typhus ecology in peninsular Malaysia.

The overall comparisons of habitats are given in (Table III). The habitats are arranged in order of extent of alterations by man, with the least disturbed at the top. The highest average blood isolation rates came from the least disturbed areas. The highest monthly maximal rickettsial isolation rates from blood and maximal prevalence rates of antibody per month were also obtained at Bukit Lanjan, the habitat least altered by activities of man. The lowest average blood isolation rate (6%) and the lowest monthly maximal rickettsial isolation and antibody prevalence rates were obtained at Bukit Mandol, the habitat most extensively and intensively altered by man. The intermediate habitats had intermediate rates. We caution anyone interpreting these observations, however, in terms of human disease, which seem to be associated with hyperendemic foci. Here we are not dealing with hyperendemicity from the standpoint of human disease, but present evidence of widespread endemicity from which hyperendemic foci may derive. Also, we have not yet identified the prevalent strains and do not know their infectivity to man.

Animals↗
PubMed1975

Influenza alone and in sequence with pneumonia due to Streptococcus pneumoniae in the squirrel monkey.

Squirrel monkeys (Saimiri sciureus) inoculated intratracheally with 10(4.2)-10(8.2) egg median infectious doses (EID50) of type A influenza virus (H3N2) responded with clinical illness including such signs as fever, sneezing or coughing, coryza, and increased respiratory rates. Necropsy studies performed six days after inoculation revealed bronchopneumonia in addition to a mild tracheitis. Squirrel monkeys given 10(5)-6 x 10(8) colony-forming units (cfu) of Streptococcus pneumoniae intratracheally died four to six days later after developing severe illness characterized by fever, bacteremia, lethargy, anorexia, coughing, labored breathing, and bronchopneumonia. Monkeys given 770 cfu of S. pneumoniae responded with less severe symptoms and survived. Four squirrel monkeys inoculated with 10(8.2) EID50 of virus and then 102 hr later with 770 cfu of S. pneumoniae developed severe disease; three of the four animals died within 40 hr. At necropsy these monkeys had more extensive and severe bronchopneumonia than was seen in monkeys infected with either organism alone.

Animals↗