Biomedical subjects

J W Dominik

Publications and source records attributed to J W Dominik.

12 recordsLinked to original sources

PubMed1984

Effect of environmental factors on aerosol-induced Lassa virus infection.

Previous studies suggested that the most frequent means of transmission of Lassa virus was by either direct or indirect contact with infectious material. Aerosol stability and respiratory infectivity of the Josiah strain of Lassa virus were assessed to determine the effect of environmental factors on aerosol-induced infection. The stability of the virus in aerosol, particularly at low relative humidity (30% RH), plus the ability of the virus to infect guinea pigs and monkeys via the respiratory route emphasize the potential for aerosol transmission of Lassa virus. Biological half-lives at both 24 and 32 degrees C ranged from 10.1 to 54.6 min, and were sufficient for aerosol dispersion of virus to considerable distances in natural situations. Infectivity of Lassa virus in small particle aerosol was demonstrated in outbred guinea pigs and cynomolgus monkeys using dynamic aerosol equipment. Monkeys exposed to inhaled doses to 465 PFU were infected and died. The median infectious dose (ID50) for guinea pigs was 15 PFU, yet a definitive median lethal aerosol dose (LD50) could not be established. Organ tropism of aerosol-induced Lassa virus infections in outbred guinea pigs was similar to that previously reported for inbred guinea pigs infected by subcutaneous inoculation.

Aerosols↗

PubMed1981

Respiratory infectivity of a recently isolated Egyptian strain of Rift Valley fever virus.

The respiratory infectivity of a strain of Rift Valley fever virus isolated in Egypt (strain ZH-501) was compared with that of one isolate from Uganda (Entebbe strain) and two isolates from South Africa (strains SA-51 and SA-75). Studies were performed with ICR mice which were infected by exposure to infectious aerosols composed of particles with a mass median diameter of 0.96 micrometer. The respiratory median lethal doses for ZH-501, Entebbe, SA-51, and SA-75 were 2.2, 1.9, 2.6, and 1.9 log10 plaque-forming units, respectively. Although these values are statistically different, the biological implications of such differences seem unimportant. In an additional study of pathogenesis, a single group of mice was infected with 3.1 log10 plaque-forming units of ZH-501, and tissues were assayed sequentially through 96 h postinfection. Between 6 and 30 h, demonstration of an increasing virus concentration only in the lungs indicated that initial replication occurred there; however, determination of histopathological changes did not reveal evidence of pneumonia. Virus was isolated from the liver by 48 h, and the ultimate outcome of infection was a fulminating and fatal hepatic necrosis.

Aerosols↗

PubMed1980

Aerosol stability and respiratory infectivity of japanese B encephalitis virus.

Experiments were conducted to examine the aerosol stability and respiratory infectivity of Japanese B encephalitis virus. At 75 degrees F (about 24 degrees C), survival of the virus as aerosol was inversely related to relative humidity. After correction for physical decay, the mean virus half-lives of the virus were 28, 38, and 62 min at relative humiditis of 80, 55, and 30%, respectively. Virus recoveries as aerosol at 4 min aftr dissemination generally exceeded the theoretical limit of 100%, based on the amount disseminated, to suggest that the process of dissemination operated to deagglomerate or release bound virus from the tissue cells in suspension. Swiss-ICR mice and golden Syrian hamsters were highly susceptible to lethal infections after respiratory challenge. Hartley strain guinea pigs and Fisher-Dunning rats, although infected, based on seroconversion observations, survived the infections. Deaths occurred in squirrel monkeys only after exposure to a high aerosol dose of virus (10(6.0) plaque-forming units). Studies of the virus concentration dynamics and histopathological findings in mouse tissues after aerosol challenge supported a hypothesis for direct transport of virus across the foramina of the cribriform plate to the tissues of the central nervous system to produce primary encephalitis.

Aerosols↗

PubMed1980

Effects of intravenous and aerosol administration of crude Shigella toxin to rhesus macaques: preliminary study.

Experiments were conducted to determine the dose response, survival time, blood biochemical changes, and cardiohepatic responses to a single IV injection of crude Shigella toxin in rhesus macaques (Macaca mulatta). Circulatory shock, hepatic falure, respiratory depression, dyspnea, convulsions, and coma were observed before death. The survival time was inversely related to the administered toxic dose, which ranged from 20 to 200 microgram/kg of body weight. However, the severity of lesions in the heart and gastrointestinal tract was directly correlated with the amount of the injected dose. Macaques exposed to aerosols of crude Shigella toxin did not show any signs of toxicosis within 7 days after exposure and were considered permanent survivors. Seemingly, an IV crude preparation of Shigella toxin is lethal to rhesus macaques, but an aerosol crude preparation of Shigella toxin is not.

Aerosols↗

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

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

Effects of small-particle aerosols of rimantadine and ribavirin on arterial blood pH and gas tensions and lung water content of A2 influenza-infected mice.

The respiratory pathophysiology of A2 influenza infection was studied in mice treated with small-particle aerosols (SPA) of rimantadine or ribavirin. Untreated infections in mice resulted in survival rates of 15% or less and were characterized by (i) severe hypoventilation (decreased P(O2) and increased P(CO2)), (ii) compensated respiratory acidosis (increased P(CO2) and HCO(3) (-), with normal pH), (iii) pneumonia with increased ratio of wet/dry lung weight, and (iv) hypothermia. Treatment with SPA of rimantadine (21 mg/kg per day for 4 days) beginning 72 h after virus challenge significantly improved survival rate (80%) but failed to alter lung pathology from that found in infected, untreated mice. Rimantadine treatment decreased somewhat the severity of hypoventilation, respiratory acidosis, lung wet weight, hypothermia, and lung virus titers from that observed in infected, untreated mice. SPA of ribavirin (26 mg/kg per day for 4 days) initiated 6 h after SPA exposure of mice to virus significantly improved survival rate (95%) and reduced lung virus titers and lung pathology. Gas exchange and pulmonary edema in ribavirin-treated, infected mice were significantly improved over those of infected, untreated controls. The mechanisms for increased survival rates induced by SPA of rimantadine remain uncertain, since increased survival rates could not be ascribed entirely to improvements in lung functions. In contrast, however, ribavirin treatment appeared to improve survival rates by reducing major lung pathology and pulmonary dysfunction. This was probably mediated through the antiviral effects of ribavirin.

Adamantane↗

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

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

Influenza virus population dynamics in the respiratory tract of experimentally infected mice.

Virus population dynamics in the lungs, trachea, and nasopharynx of Swiss-ICR mice were studied after respiratory challenge with mouse-adapted preparations of strain A2/Aichi/2/68 influenza virus. Markedly higher doses of virus were required to produce infection with nasopharyngeal challenge than with bronchoalveolar challenge. In all of the infections, the highest virus concentrations were observed in the lungs. Peak concentrations in the trachea were lower than in the lungs but higher than in the nasopharynx. Decreasing virus levels were observed by 120 h after challenge and were generally below detectable levels by the end of 10 days. A compartmental model of a single mathematical form was developed which provided close fits of the virus concentration measurements regardless of the challenge dose, site of initial deposition, or respiratory tissue considered. The model includes seven compartments with five associated rate parameters. The application of compartmental modeling techniques and expression of the virus population dynamics in mathematical terms is regarded as a new approach to the study of the pathogenesis of infections.

Administration, Intranasal↗

PubMed1975

Treatment of influenza infection of mice by using rimantadine hydrochlorides by the aerosol and intraperitoneal routes.

Rimantadine hydrochloride was administered for 4 days in a small-particle (95% < 6.5 mum) aerosol (8.8 mg/kg per day) or intraperitoneally (40 mg/kg per day) to mice previously infected with influenza A/Aichi/2/68 (H(3)N(2)), mouse adapted. Mean time to death and incidence of survival were significantly increased in all treated groups of mice. The rate of eventual disappearance of virus from lung tissue was also accelerated by therapy. However, maximal mean virus titer per lung, and lung histopathology, did not reveal any difference between control and either group of treated mice. Aerosol therapy initiated at 72 h postinfection was as effective as that initiated at 6 h, even though lung virus titers of these mice had already peaked by 72 h. In contrast, intraperitoneal therapy initiated at 72 h was not effective in all studies.

Adamantane↗

PubMed1974

Modified spinning top homogeneous spray apparatus for use in experimental respiratory disease studies.

The May spinning top generator was adapted to a modified Henderson tube for producing large aerosol particles (>4 mum) to obtain almost exclusive upper respiratory tract deposition of infectious aerosols in exposed mice. The system was installed in a biological safety cabinet to permit experimentation with pathogens. A novel mechanism utilizing parts from a machinists micrometer and the mechanical stage from a light microscope was developed for the spinning top generator as a means for precisely positioning the liquid feed needle. Aerosol light-scatter properties were continuously analyzed to provide relative measures of particle size distribution and aerosol concentration. When mice were exposed to influenza virus aerosols in which none of the virus was contained in particles with aerodynamic diameters <4 mum, essentially all of the virus was deposited in the upper respiratory tract tissues.

Aerosols↗