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Biomedical subjects

D E Hilmas

Publications and source records attributed to D E Hilmas.

At least 19 recordsLinked to original sources

Beryllium sensitization and chronic beryllium disease at a former nuclear weapons facility.

The prevalence of beryllium sensitization and chronic beryllium disease by job category was examined among individuals tested in the Rocky Flats Beryllium Health Surveillance Program. The program offered ongoing beryllium health surveillance for any current or former employee who believed they may have been exposed to beryllium at the Rocky Flats Environmental Technology Site. Of the 18,589 living individuals contacted, 7,573 requested participation and 6,614 (87.3%) eventually participated. Of this group, 78.2 percent were found to have verifiable job and building histories. The beryllium lymphocyte proliferation test was used to identify beryllium-sensitized individuals. Sensitization and chronic beryllium disease rates were analyzed with respect to gender, building work location(s), and length of employment at Rocky Flats. Several job categories and buildings were strongly associated with the 81 cases of chronic beryllium disease and the additional 154 cases of beryllium sensitization in this population. Beryllium sensitization was highest among beryllium machinists, 11.4 percent (odds ratio = 3.04, compared to the remainder of those tested, 95 % confidence interval = 1.48, 3.97) and health physics technicians, 11.9 percent (odds ratio = 2.87, 95% confidence interval = 1.12, 7.36). However, odds ratios were also increased among custodial employees, 5.64 percent (odds ratio = 1.30, 95% confidence interval = 0.92, 1.85) and other job titles that were thought to have only minimal potential for exposure to beryllium.

Berylliosis↗

Former radiation worker Medical Surveillance Program at Rocky Flats.

The United States Department of Energy (DOE), Office of Occupational Medicine and Medical Surveillance, has supported an ongoing Former Radiation Worker Medical Surveillance Program at the DOE Rocky Flats site since 1992. The program currently is managed for DOE by Oak Ridge Institute for Science and Education through a contract with Oak Ridge Associated Universities. Participation in the program is entirely voluntary and provides former Rocky Flats workers who were exposed to radiation with long-term medical monitoring and an update to the assessment of their radiation dose. Program participants receive medical examinations and in vivo and in vitro bioassay measurements of residual radioactivity. Radiation doses to participants are largely a result of internal depositions of plutonium and its radioactive decay products. The causes of many of the higher internal doses were accidents that generally are well documented. Former radiation workers are invited to participate in the program if they meet specific criteria for radiation exposure. Informed consent is documented using a consent form approved by an Institutional Review Board. Demographic, medical, and dosimetric information is maintained in a computer database and will be evaluated for any trends or correlations between exposure and health outcome.

Adult↗

Possible health risks from low level exposure to beryllium.

The first case of chronic beryllium disease (CBD) at the Rocky Flats Environmental Technology Site (Rocky Flats) was diagnosed in a machinist in 1984. Rocky Flats, located 16 miles northwest of Denver, Colorado, is part of the United States Department of Energy (DOE) nuclear weapons complex. Research and development operations using beryllium began at Rocky Flats in 1953, and beryllium production operations began in 1957. Exposures could have occurred during foundry operations, casting, shearing, rolling, cutting, welding, machining, sanding, polishing, assembly, and chemical analysis operations. The Beryllium Health Surveillance Program (BHSP) was established in June 1991 at Rocky Flats to provide health surveillance for beryllium exposed employees using the Lymphocyte Proliferation Test (LPT) to identify sensitized individuals. Of the 29 cases of CBD and 76 cases of beryllium sensitization identified since 1991, several cases appear to have had only minimal opportunistic exposures to beryllium, since they were employed in administrative functions rather than primary beryllium operations. In conjunction with other health surveillance programs, a questionnaire and interview are administered to obtain detailed work and health histories. These histories, along with other data, are utilized to estimate the extent of an individual's exposure. Additional surveillance is in progress to attempt to characterize the possible risks from intermittent or brief exposures to beryllium in the workplace.

Berylliosis↗

Rocky Flats Beryllium Health Surveillance.

The Rocky Flats Beryllium Health Surveillance Program (BHSP), initiated in June 1991, was designed to provide medical surveillance for current and former employees exposed to beryllium. The BHSP identifies individuals who have developed beryllium sensitivity using the beryllium lymphocyte proliferation test (BeLPT). A detailed medical evaluation to determine the prevalence of chronic beryllium disease (CBD) is offered to individuals identified as beryllium sensitized or to those who have chest X-ray changes suggestive of CBD. The BHSP has identified 27 cases of CBD and another 74 cases of beryllium sensitization out of 4268 individuals tested. The distribution of BeLPT values for normal, sensitized, and CBD-identified individuals is described. Based on the information collected during the first 3 1/3 years of the BHSP, the BeLPT is the most effective means for the early identification of beryllium-sensitized individuals and to identify individuals who may have CBD. The need for BeLPT retesting is demonstrated through the identification of beryllium sensitization in individuals who previously tested normal. Posterior/anterior chest X-rays were not effective in the identification of CBD.

Berylliosis↗

Sarin intoxication elevates plasma pralidoxime.

Groups of guinea pigs were injected with a range of dosages for sarin (0, 140, 279, 557 micrograms/kg) followed by pralidoxime (2-PAM) and atropine sulfate (16 mg/kg). Poisoning by sarin in these animals elevated plasma pralidoxime content in a dose-dependent manner within 10 min of intoxication. Plasma levels after administration of 3.12 mg/kg of 2-PAM were elevated from a control mean of 6.18 micrograms/ml to a maximum of 13.78 micrograms/ml in animals given 557 micrograms/kg of sarin at 2 min after the injection of the therapeutic compounds. This suggests that pathophysiological changes following intoxication by potent inhibitors of cholinesterase result in a decrease in the rate and extent of distribution of therapeutic compounds. This effect is most likely a consequence of changes in cardiovascular functions influencing blood flow to various organs.

Animals↗

Protective and toxic effects of a nuclease-resistant derivative of polyriboinosinic-polyribocytidylic acid on Venezuelan equine encephalomyelitis virus in rhesus monkeys.

Polyriboinosinic-polyribocytidylic acid, stabilized with poly-L-lysine and carboxymethylcellulose (poly ICLC), favorably alters the pathogenesis of Venezuelan equine encephalomyelitis virus infection in rhesus monkeys by decreasing the number of infected monkey that become detectably viremic and by delaying the onset of viremia in the remaining monkeys. Poly ICLC is known to induce high circulating levels of interferon in primates, and the interferon system is assumed to be the mechanism by which poly ICLC exerts its antiviral effect. Poly ICLC treatment was associated with a few deaths, but only under certain conditions of infection and handling. The death of some infected, treated monkeys in the absence of death in monkeys that were either infected and untreated or treated and uninfected suggests a synergistic toxicity resulting from the combination of infection, handling, and poly ICLC treatment, although other explanations are possible.

Animals↗

Adjuvant effects of low doses of a nuclease-resistant derivative of polyinosinic acid . polycytidylic acid on antibody responses of monkeys to inactivated Venezuelan equine encephalomyelitis virus vaccine.

Polyriboinosinic.polyribocytidylic acid [poly(I).poly(C)] stabilized with poly-l-lysine and carboxymethylcellulose [poly(ICLC)] has been previously shown to be a compound with marked adjuvant activity when given in high doses with inactivated Venezuelan equine encephalomyelitis (VEE) virus vaccine. This study investigated the effects of much lower doses of poly(ICLC) on the magnitude and kinetics of the primary and secondary humoral antibody responses of rhesus monkeys to inactivated VEE virus vaccine. Monkeys given a single injection of vaccine developed very low neutralizing antibody titers, whereas those given adjuvant plus vaccine had 30- to 100-fold-higher titers which remained elevated for longer than 6 months. Low doses of poly(ICLC) given with VEE virus vaccine resulted in a profound but transient increase in priming of secondary antibody responses to the antigen. In contrast, the administration of poly-l-lysine and carboxymethylcellulose alone without the poly(I).poly(C) component of the complex had no adjuvant effect on antibody responses of monkeys to VEE virus vaccine. The temporal development of antibody by class (immunoglobulin M-immunoglobulin G) in monkeys given two injections of adjuvant-vaccine was not different from that with vaccine alone. Serial hematological and clinical chemistry determinations on monkeys given single or multiple doses of poly(ICLC) with vaccine were not different from values in monkeys given vaccine alone.

Adjuvants, Immunologic↗

Alterations of body fluid compartments and distribution of tissue water and electrolytes in rhesus monkeys with rocky mountain spotted fever.

Chair-restrained rhesus monkeys (Macaca mulatta) were inoculated subcutaneously with 10(2)--10(3) plaque-forming units of virulent Rickettsia rickettsii. The latent period for fever and rickettsemia was three to four days; death occurred six to eight days after infection. Total circulatory electrolyte levels and fluid volumes, including plasma, red blood cell, true circulatory blood, and extracellular fluid, increased. The expansion of the extracellular and plasma volumes resembled findings reported during severe Rocky Mountain spotted fever in humans, guinea pigs, and rabbits. Total water content of the liver also increased. Intracellular concentrations of K+, as well as total Na+ and K+, decreased in the diaphragm. Both the lung and medulla oblongata showed increased levels of intracellular Na+ and water with simultaneously decreased levels of extracellular Na+ and water. Such an intracellular overhydration of the medulla oblongata could contribute to death as a result of depression of the cardiovascular and respiratory centers. On the basis of the findings in monkeys, the intravenous infusion of fluids and electrolytes during clinical therapy of severe rickettsial infections should be considered extremely dangerous.

Animals↗

Studies of the coagulation system and blood pressure during experimental Bolivian hemorrhagic fever in rhesus monkeys.

Experimental infection of rhesus monkeys (Macaca mulatta) with Machupo virus produced a hemorrhagic disease similar to that of Bolivian hemorrhagic fever in humans. The disease in infected animals was also characterized by the development of hypotension and coagulation abnormalities as indicated by severe thrombocytopenia and prolongation of the activated partial thromboplastin time. Evidence for disseminated intravascular coagulation was inconclusive due to the presence of normal to elevated fibrinogen levels, relatively low levels of circulating fibrin split products, and the lack of widespread fibrin thrombus deposition. The most likely causes of the hemorrhagic tendencies of this disease in infected monkeys were thrombocytopenia and decreased synthesis of coagulation and other plasma proteins due to severe hepatocellular necrosis. Hypotension may also have been due to decreased plasma protein synthesis.

Animals↗

Femoral venipuncture for repeated blood sampling in miniature swine.

Repetitive blood sampling of miniature swine was accomplished by percutaneous puncture of the femoral vein. Swine were restrained manually in dorsal recumbency. The skin was penetrated in the inguinal area approximately 2.5 cm laterally to the most posterior mammary gland with a 21-gauge, 3 cm (1.5 inch) needle. Ten milliliters of blood were withdrawn of frequent intervals for 4 months without apparent harm to the animals.

Animals↗

Effect of staphylococcal enterotoxin B on cardiorenal functions and survival in X-irradiated rhesus macaques.

Pretreatment of rhesus macaques with nonlethal total-body x-irradiation (400 R) prolonged survival time from an average of 15 hours to 101 hours after intravenous (IV) inoculation of 50 microgram of staphylococcal enterotoxin B (SEB)/kg of body weight. Radiation exposure per se did not produce detectable cardiorenal changes; however, the longer survival after SEB challenge exposure in x-irradiated rhesus macaques was associated with improved cardiorenal functions if compared with that of nonirradiated macaques given the same dose of SEB. Total-body radiation exposure 4 days prior to IV SEB inoculation prevented typical SEB-induced decreases (where measured at 5 hours) in cardiac output, stroke volume, TcH2O, CPAH, Cosm, and urine flow, as well as increases in total peripheral and renal resistance. A theory concerning the significance of radiation-induced leukopenia on modification of SEB-induced cardiorenal functions is postulated.

Animals↗

Swine influenza virus vaccine: potentiation of antibody responses in rhesus monkeys.

Polyriboinosinic-polyribocytidylic acid stabilized with poly-L-lysine and carboxymethylcellulose [poly(ICLC)] enhances the antibody response in rhesus monkeys immunized with swine influenza virus subunit vaccine. Monkeys given the vaccine-adjuvant combination had earlier and significantly (P less than .05) higher titers by 14 days compared to those that received vaccine alone. The potentiation of the antibody response of young monkeys given a split-virus vaccine in combination with poly(ICLC) suggests that this vaccine-adjuvant combination may similarly provide a potentially useful alternative approach to the immunization of pediatric and young adult age groups against swine influenza.

Adjuvants, Immunologic↗

Vascular clearance of venezuelan equine encephalomyelitis viruses as a correlate to virulence for rhesus monkeys.

The epizootic Trinidad donkey strain of Venezuelan equime encephalomyelitis virus (VEE) was cleared slowly from the circulation of rhesus monkeys following intravenous inoculation, while the live, attenuated vaccine strain, TC-83, was cleared rapidly. The efficent clearance of TC-83 vaccine may be a factor in the lower viremia and benign course of TC-83 virus infection in rhesus monkeys.

Animals↗

Interferon induction in cynomolgus and rhesus monkey after repeated doses of a modified polyriboinosinic-polyribocytidylic acid complex.

Serum interferon activity was determined in 12 cynomolgus and 12 rhesus monkeys injected intravenously once daily for 10 days with from 0.1 to 6.0 mg of a stabilized polyriboinosinic acid . polyribocytidylic acid complex per kg, composed of polyriboinosinic acid . polyribocytidylic acid, poly-1-lysine, and carboxymethylcellulose [poly(ICLC)]. Interferon activity was detected 2 h after the first injection, with maximum activity occurring 8 h after the second injection. A period of hyporesponsiveness occurred after the third injection of poly(ICLC) in all monkeys and lasted until the sixth injection in the rhesus monkeys, when interferon activity again became more elevated. The delayed rebound was not as apparent in cynomolgus monkeys. Rhesus monkeys injected with 6 mg/kg did not exhibit serious side effects.

Animals↗