In previous studies of the response of normal volunteers to inoculation with respiratory viruses, the inoculum was administered by instillation of liquid into the nose and by a hand nebulizer that delivered a coarse spray to the nasopharynx (1). Observation indicated that much of the virus given by these methods deposited in the nasopharynx, but portions were swallowed, or discharged by coughing, sneezing, or expectoration. Although these studies often resulted in viral infection and illness, it was not possible to assess accurately dose-effect relationships. Furthermore, it was apparent that a full investigation of human response to respiratory viruses should include observations on the effect of inoculation of portions of the respiratory tract other than the nasopharynx.Inoculation with aerosol offered the possibility of attaining the above objectives. The site of deposition of particles within the respiratory tract and the number of particles deposited is a function of the particle size (2, 3). It is thus possible to estimate with some accuracy both the site of viral deposition and the amount of virus deposited when aerosols of known particle size containing known amounts of virus are inhaled. Therefore, when preliminary studies demonstrated the feasibility of the use in human volunteers of a small-particle aerosol containing Coxsackie A21 virus (4), and the properties of the aeorsol had been determined (5), observations were made on the response of volunteers to graduated doses of the aerosol utilizing three different inocula of Coxsackie A21.
818COXSACKIE Azl AEROSOL Rowever, the available data are merely suggestive and further experiments are needed to prove this supposition. If this hypothesis is correct, adrenalectomy (with substitution for lack of mineral corticoids) should increase the incidence of non-thymic lymphomas in neonatally thymectomized hosts.The incidence of myeloid leukemias was markedly increased by thymectomy in our earlier experiment( 1) and in those by Gross (12). In the present experiment only one case of myeloid leukemia was found in 106 thymectomized virus-infected rats. It occurred in a thymectomized rat with an implanted empty Millipore chamber. The lower incidence of myeloid leukemia in the present experiment (less than 1%) compared with 12% in our earlier experiment (1) is puzzling. We expected a higher incidence because more rats escaped early deaths from non-thymic lymphomas (cf. 6 ) . Failure of thymectomized rats to develop myeloid leukemia in the present experiments may be explained by low concentration of the virus. The thymus is a favored organ for replication of the virus ( 2 ) . If so, neonatal thymectomy prior to virusinfection as done in the present experiments, eliminates this effect of thymus and neonatally thymectomized rats might be expected to have less virus than rats infected with virus first and thymectomized one month later. month after virus-infection( 1 ) originated in cells which have been transformed in the thymus and seeded in other lymphoid organs prior to thymectomy. 3. The data also suggest a) that non-thymic lymphomas may be induced by the virus and b) that stressful agents which cause corticoid discharge might lower not only the incidence of the thymic, but also the non-thymic lymphomas.We acknowledge the able assistance of Miss Sandra
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