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Biomedical subjects

D E Hilmas

Publications and source records attributed to D E Hilmas.

33 records · Page 2Linked to original sources
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

An easily dismantled pig pen for long-term radiation exposure.

A pen to hold individual miniature pigs during long-term radiation exposure studies has been designed and used. Wooden construction results in low cost and minimizes radiation scatter problems associated with higher density materials. An automatic water system is provided.

Animals↗
PubMed1977

Modification of Venezuelan equine encephalomyelitis virus infection in mice by X radiation.

A highly virulent strain of Venezuelan equine encephalomyelitis (VEE) virus produced less severe histopathologic changes in brain tissues of mice previously exposed to sublethal total-body x-irradiation than it caused in nonirradiated mice. Prior exposure to 600 R of x-irradiation virtually eliminated the lesions of vasculitis and encephalitis that were found in the infected nonirradiated control mice. Mean peak brain lesion scores generally decreased as radiation exposure dose was increased. Irradiation of mice before inoculation often decreased median time to death, whereas the severity of pathologic changes in brain tissues from inoculated irradiated mice was often reduced, without significantly altering ultimate host survival. The inflammatory response did not appear to have a significant role in clearance of this virus from the brain. There was no evidence that participation of the immune response contributed to total mortality from VEE virus encephalitis, as indicated by the failure of radiation immunosuppression to reduce mortality. Death apparently was caused by the direct cytocidal effects of VEE virus replication.

Animals↗
PubMed1976

Radiotherapy of spontaneous fibrous connective-tissue sarcomas in animals.

The clinical records and follow-up data obtained over 13 years on the results of radiotherapy of spontaneous fibrous connective-tissue sarcomas in dogs, cats, and horses were reviewed. The results obtained from the treatment of fibrosarcomas and sarcoids of horses indicated that radiation administered with 60Co is important in the medical and surgical management of these tumors. Fibrous connective-tissue sarcomas in horses were radioresponsive. When radiotherapy was applied postoperatively, the probability of a 2-year cure approached 50% for all prescribed radiation doses of less than 2,000 to greater than 4,000 rads. If radiation doses of 4,500-6,000 rads were used, a 2-year cure rate may approach or exceed 60%.

Animals↗
PubMed1976

Serum lactate dehydrogenase of normal, stressed, and yellow fever virus-infected rhesus monkeys.

Serum lactate dehydrogenase enzyme (sLDH) was studied in both healthy and yellow fever virus (YFV)-infected young adult rhesus monkeys (Macaca mulatta). In healthy monkeys, significant variation (p less than 0.001) was observed for both total activity and isoenzyme distribution among the following comparisons: individual monkeys, different days, different times of day, and caged versus chair-restrained monkeys (until 7 da after chair restraint). However, variability of baseline values was reduced by the use of samples obtained from resting subjects at 9:00 am on at least 3 consecutive days. Normal total activity and isoenzyme distribution values were based on 148 determinations obtained from 73 healthy, caged monkeys. Both total activity and the proportion of the 5th isoenzyme fraction increased significantly (p less than 0.001) in the YFV-infected monkeys, beginning 90 hr postinfection, consistent with hepatocellular necrosis and release of isoenzymes into the serum. The assay for sLDH appears to be of value as a diagnostic indicator during the course of YFV infection in the rhesus monkey.

Animals↗
PubMed1975

Response of irradiated mice to live-virus (TC-83) immunization.

Studies were conducted to determine the effects of sublethal, acute, total-body irradiation (600 R) on the immune response of mice to a replicating antigen. Irradiation was performed at varying times (0 to 21 days) prior to immunization with attenuated Venezuelan equine encephalomyelitis virus, TC-83. Development of protective immunity was studied by inoculating subgroups of irradiated mice with virulent Venezuelan equine encephalomyelitis virus on days 1 through 28 after immunization. Irradiation failed to affect the overt clinical response of mice inoculated with the attenuated strain, but antibody responses and the onset of protective immunity was delayed, particularly in mice irradiated 2 h to 3 days prior to vaccination. Immunity afforded by TC-83 developed more rapidly as the interval between irradiation and vaccination increased: when this interval was 14 or more days, the temporal course of immune response in irradiated mice was similar to that of nonirradiated vaccines. Persistence of TC-83 viremia was greatly prolonged in irradiated mice through the irradiation recovery period and probably provided the antigenic stimulus responsible for delayed development of effective immunity.

Animals↗
PubMed1975

Response of sublethally irradiated monkeys to a replicating viral antigen.

Temporal effects of exposure to sublethal, total-body X radiation (400 R) on responses to vaccination with attenuated Venezuelan equine encephalomyelitis vaccine virus. TC-83, were examined in rhesus monkeys. Viremia, often with delayed onset, was prolonged even when irradiation preceded vaccination by 28 days. Virus titers were increased, articularly in groups irradiated 4 or 7 days before vaccination. Delay in appearance of hemagglutination-inhibition and serum-neutralizing antibody correlated closely with persistence of viremia in irradiated-vaccinated monkeys. The temporal course of antibody response was markedly affected by the intervals between irradiation and injection of this replicating antigen. With longer intervals between irradiation and vaccination, the somewhat depressed antibody responses approached normal or surpassed those of nonirradiated monkeys. Vaccination 14 days after radiation exposure resulted in lethality to 8 of 12 monkeys, apparently as a result of secondary infection. The additional lymphopenic stress due to the effect of TC-83, superimposed on the severly depressed hematopoietic competence at 14 days, undoubtedly contributed to this increased susceptibility to latent infection.

Animals↗
PubMed1975

Tumor microvasculature following fractionated x irradiation.

The microvasculature of C3H/Bi mouse mammary carcinomas 8 mm in average diameter was evaluated using morphometric methods following six consecutive daily exposures of 500 R of x radiation. Tumor volume did not change significantly during the intervals between treatments. Tumors began to grow again 72 hours after the sixth 550-R fraction, with mean vessel length and surface area reaching maximum values and vessel diameters and volumes becoming minimal at this time. These changes were attributed to improved colloidal-carbon filling of previously existing nonfunctional vessles. When anatomically derived estimates of vascular dimensions were related to a metabolically useful blood supply, improved capability for exchange of essential nutrients occurred 72 hours after the sixth 500-R fraction.

Animals↗
PubMedDate not supplied

Application of beryllium antibodies in risk assessment and health surveillance: two case studies.

This paper demonstrates that current standards used by the Occupational Safety and Health Administration (OSHA) to establish an area free from potential beryllium contamination may be inadequate. Using the Beryllium Antibody Assay, it was shown that workers exposed to former beryllium work areas, thought to be sanitized and to meet OSHA standards, experienced statistically significant rises in blood beryllium antibody titers. This finding raises the question of whether the equipment currently required to protect workers in beryllium-laden environments is sufficient. The project mission of decommissioning/decontaminating the former nuclear weapons plant at Rocky Flats Environmental Technology Site (RFETS), instituted in 1992, has necessitated development of new technology directed toward safe and responsible cleanup. Challenges have been posed not only by the need to dispose of radioactive and chemical waste, but also by the problem of cleaning up hazardous metals such as the element beryllium. Beryllium was used extensively in research and the manufacture of nuclear weapons components at Rocky Flats for over 40 years. Since inhalation of this element can induce chronic beryllium disease (Eisenbud and Lisson, 1983), an antibody assay was developed to screen workers for internal exposure to beryllium. Exposure is indicated by a titer of antibodies greater than two standard deviations above a normal population control (defined as the mean titer of pooled samples from 51 individuals with no known exposure to beryllium) and a p-value of < 0.05. This paper describes two new applications for the assay: risk assessment and health surveillance. Case study 1 involves a team of three workers who cleaned a beryllium plenum and whose beryllium antibody titers provided a quantitative assessment of their exposure. Case study 2 describes the use of the antibody assay to determine the probable manner in which one worker was exposed to beryllium while performing his duties as an architectural engineer.

Air Pollutants, Occupational↗