PubMed Health⌕ Search

Biomedical subjects

M L Pitt

Publications and source records attributed to M L Pitt.

27 records · Page 2Linked to original sources
PubMed1996

Steady-state minute volume determination by body-only plethysmography in juvenile rhesus monkeys.

When one is using nonhuman primates for studying the inhalation of infective or toxic agents, a respiratory minute volume (MV) range of +/- 50 ml is desirable to ensure the accurate delivery of calculated doses of the aerosolized agent. When one is working with highly infective or toxic agents, it is desirable to anesthetize the animals and to separate the plethysmograph, used to measure MV, from the aerosol chamber, used to administer agents, in order to minimize decontamination procedures and to maximize safety. In our laboratory the sequential completion of these procedures requires at least 20 min. Therefore it is necessary to find an anesthetic that achieves a +/- 50 ml steady-state MV for at least 20 min and that does not change when an animal is transported from one apparatus to another. Using 2.6- to 4.0-kg, 14- to 18-month-old rhesus macaques, we determined that tiletamine/zolazepam induced a steady-state MV of 48 +/- 17.8 min, beginning 21.5 +/- 4.7 min after injection of the anesthetic agent. This MV did not significantly change when animals were transported. The use of ketamine and ketamine/acepromazine resulted in a steady-state MV period of 11.5 +/- 4.5 and 22.0 +/- 7.9 min respectively. When we compared these findings with previously reported mathematical estimations of MV based on functions of weight or respiratory rate, we further determined that the accurate measurement of MV before each aerosol exposure was critical for calculating inhaled doses of the agent.

Acepromazine↗
PubMed1995

The distribution of [125I]ricin in mice following aerosol inhalation exposure.

Studies were conducted to examine the uptake and redistribution of [125I]ricin from the lungs of mice following nose-only aerosol inhalation exposure. Radiolabelled contents were measured in lung and various extra-pulmonary tissues 15 min through 30 h following 10 min aerosol exposures. Pharmacokinetic analyses were performed on whole-organ data obtained for lungs, stomach, liver and spleen. Radioactivity within the lungs, maximal at 15 min post-exposure, was eliminated in a biexponential fashion with a long beta half-life (approximately 40 h). Large amounts of radiolabel were also found within the gastrointestinal tract. Radiolabel within the stomach exhibited an absorption phase and two-compartment elimination. Radiolabel content of many other tissues, including known accumulation sites for intravenously administered toxin, was significantly (p < 0.05) increased (relative to 15 min post-exposure) in association with the early elimination of radiolabel from the lungs, but levels in these tissues were very low and did not increase after 4 h post-exposure. The only exception was our sample of trachea, which showed delayed elevations in radiolabel (peak at 24 h); this pattern was attributable to the contained thyroid (not removed at necropsy) and its trapping of free [125I] released upon tissue [125I]ricin degradation. The overall data indicate that ricin administered by aerosol inhalation is delivered to both respiratory and gastrointestinal tracts; however, it is not extensively transported from either tract to other potential target sites. Ricin delivered to the lungs is primarily sequestered within the lungs until degradation. Only small amounts of ricin delivered to the gastrointestinal tract are absorbed into the circulation.

Administration, Inhalation↗
PubMed1995

Relationship between virulence and immunity as revealed in recent studies of the F1 capsule of Yersinia pestis.

Yersinia pestis, the causative agent of plague, possesses multiple virulence determinants encoded on its three plasmids and on its chromosome. We evaluated the role of the protein capsule F1 in virulence an immunity against plague. Strains lacking F1, either those that are naturally occurring or those with genetically defined nonpolar mutations in the structural gene, retained their virulence for mice and nonhuman primates. However, both active immunization with F1, from either a recombinant vector or Y. pestis, and passive immunization with F1 monoclonal antibody protected mice from experimental infection with wild-type F1-positive organisms. These results suggest that protective immunogens like F1 need not be essential for virulence. The rare isolation of virulent F1-negative organisms from F1-immunized animals infected with F1-positive strains supports this conclusion and also suggests that, in addition to F1, an optimal vaccine against plague should include essential virulence factors as immunogens.

Animals↗
PubMed1995

Pathology of experimental inhalation anthrax in the rhesus monkey.

BACKGROUND: The inhalation form of anthrax, although rare, is nearly always fatal because of the rapid progression of the disease with little host response until the terminal stages of the disease. The Gulf War heightened the concern that anthrax could be used as a biologic weapon. Past studies modeling pathologic changes in human inhalation anthrax have used the rhesus monkey. EXPERIMENTAL DESIGN: We studied pathologic changes in the rhesus monkey model of inhalation anthrax. Gross examination as well as light and electron microscopy were used to define pathologic alterations. Immunolabeling techniques were used to identify the anthrax bacillus by light and electron microscopy. RESULTS: Gross changes included hemorrhage in mesenteric (54%) and tracheobronchial (46%) lymph nodes, meninges (38%), lungs (31%), and small intestinal serosa (31%). Histopathologic changes included suppurative meningitis (77%); hemorrhages in the meninges (54%), neuropil (31%), and pulmonary alveoli (31%); and pneumonia (15%). Spleens and various lymph nodes from all monkeys had one or more of the following changes: hemorrhage, acute inflammation, extracellular bacilli, lymphocytic depletion, and histiocytosis. Spleens of two monkeys were devoid of extracellular bacilli, but degraded intrahistiocytic bacilli reacted with Ab to Bacillus anthracis cell wall polysaccharide. CONCLUSIONS: In our study, compared with previous reports, meningitis and mesenteric lymph node hemorrhages were more common, whereas mediastinal and tracheobronchial lymph node hemorrhages were less common. Immunostaining highlighted intracellular bacilli that would have been otherwise missed by light microscopic examination.

Animals↗
PubMed1993

Postexposure prophylaxis against experimental inhalation anthrax.

Inhalation anthrax is a rare disease that is almost invariably fatal. This study determined whether a prolonged course of postexposure antibiotics with or without vaccination would protect monkeys exposed to a lethal aerosol dose of Bacillus anthracis when the antibiotic was discontinued. Beginning 1 day after exposure, groups of 10 animals were given penicillin, ciprofloxacin, doxycycline, doxycycline plus vaccination, vaccination alone, or saline. Antibiotics were administered for 30 days and then discontinued. Vaccine was given on days 1 and 15. Two animals died of causes other than anthrax and were not included in the statistical analysis. Nine of 10 controls and 8 of 10 animals given only vaccine died. Each antibiotic regimen completely protected animals while on therapy and provided significant long-term protection upon discontinuance of the drug (penicillin, 7 of 10 survived, P < .02; ciprofloxacin, 8 of 9 survived, P < .002; doxycycline, 9 of 10 survived, P < .002; doxycycline plus vaccination, 9 of 9 survived, P < .0002). Protection against rechallenge was provided by combining postexposure antibiotic treatment with vaccination.

Aerosols↗
PubMed1985

Hypersensitivity among woodworkers in South Africa.

A group of South African woodworkers was investigated in respect of allergenic activity of three indigenous woods, yellowwood, stinkwood and blackwood, and Brazilian imbuia. Histories were taken, skin-prick tests performed, and total serum IgE levels estimated. A high rate of skin sensitivity was found, as well as previously undocumented skin sensitivities to stinkwood and yellowwood.

Adolescent↗
PubMedDate not supplied

Use of telemetry to assess vaccine-induced protection against parenteral and aerosol infections of Venezuelan equine encephalitis virus in non-human primates.

Two investigational vaccines, TC-83 (live-attenuated) and C-84 (formalin-inactivated), are currently available to immunize at-risk individuals against Venezuelan equine encephalitis virus (VEE). Ideally, such vaccines should protect against both the natural mosquito-borne route of infection and from aerosol, the most common route of laboratory infection. Whereas considerable data on vaccine efficacy following parenteral challenge are available, the efficacy of these vaccines against disease caused by aerosol exposure is not well established in primates. We compared the immunogenicity and protective capacity of TC-83 and C-84 against either subcutaneous or aerosol routes of infection in cynomolgus monkeys implanted with temperature-monitoring radiotelemetry devices. A single s.c. dose of TC-83, or three s.c. doses (days 0, 7, 28) of C-84, elicited similar serum virus-neutralizing antibody responses. Animals immunized with either TC-83 or C-84 were protected against s.c. infection. In contrast, after aerosol infection, 40% of the animals vaccinated with either TC-83 or C-84 developed signs nearly as severe as those seen in unvaccinated animals. Protection was not entirely consistent with the measured preinfection immune responses: unprotected animals had serum virus-neutralizing antibody titers and lymphoproliferative responses similar to those seen in protected animals. In this study, C-84 (three doses) protected monkeys as well as TC-83 (one dose) against either a s.c. or aerosol VEE challenge.

Aerosols↗