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H W Young

Publications and source records attributed to H W Young.

5 recordsLinked to original sources

Nose-only versus whole-body aerosol exposure for induction of upper respiratory infections of laboratory mice.

The effectiveness of two aerosol delivery systems, nose-only and whole-body, were compared using Swiss-Webster mice and two pathogens, Klebsiella pneumoniae and Venezuelan equine encephalitis (VEE) virus. With K. pneumoniae the median lethal dose (LD50) and the mean time to death correlated with the inhaled dose. An LD50 value of 335 colony forming units (cfu) for nose-only exposure was significantly less than the LD50 value of 3741 cfu obtained for whole-body exposure. The LD50 values obtained with VEE virus for nose-only exposure [8 plaque forming units (pfu)] and whole-body exposure (11 pfu) were similar to each other. Following a 10-min nose-only exposure, concentrations of K. pneumoniae approximating 10(4)/g were present after 24 hr in the upper respiratory tract (URT) and lungs. The numbers of bacteria reached a peak at 72 hr, when resolution of the infection began. Detectable levels of bacteria in the blood and tissues were delayed in mice given whole-body exposure, plus there was a decreased concentration of bacteria per gram of tissue. Major pathological lesions induced by K. pneumoniae were mild suppurative rhinitis and minimal suppurative bronchopneumonia. Viremia was greatest at 96 hr following aerosol exposure to VEE. Virus concentrations in the URT, lungs, cerebrum, spleen and mesenteric lymph nodes reached maximum titers earlier for mice exposed by nose-only than for mice exposed to whole-body aerosols.(ABSTRACT TRUNCATED AT 250 WORDS)

Aerosols

Protection against Klebsiella pneumoniae respiratory tract infection of mice and squirrel monkeys given kanamycin by aerosol and injection.

The methods of aerosol administration of kanamycin and IM injection of the antibiotic were compared for their protection of mice and squirrel monkeys against Klebsiella pneumoniae respiratory tract infection. Mice exposed to LD90 of K pneumoniae at 0.5, 4, 24, 48 and 72 hours after they were treated with aerosol of kanamycin (27 mg/kg of body weight) were significantly better protected at all exposure times than were mice given the antibiotic (450 mg/kg) by IM injection. Squirrel monkeys given the aerosol at dose level of 11.25 mg/kg were completely protected against K pneumoniae exposure at 6 and 24 hours, whereas only one of eight monkeys treated with the same dose given IM survived the exposure at 6 hours and none survived at 24 hours. Antibiotic clearance curves indicated that kanamycin remained in the lungs at higher concentrations and for longer periods after aerosol treatment than after IM treatment.

Aerosols

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

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