G. Kenneth Adams

Recovery of central respiratory function following anticholinesterase intoxication

Spontaneous recovery of central respiratory function was studied in anesthetized guinea pigs intoxicated with pinacolyl methylphosphonofluoridate (Soman) or isopropyl methylphosphonofluoridate (Sarin). I.v adiministration of either agent produced an immediate disruption phrenic nerve activiity and resulting ventilatory failure. Animals were maintained on artifical respiration until spontaneous functional recovery was complete, as evidenced by the re-establishment of synchronized burst activity on the phrenic nerve and return of tracheal airflow. This usually occurred within 1 h. Animals were sacrificed at predetermined intervals after intoxication, and the brainstem homogenates were analyzed for AChE activity. Results showed no significant return of AChE activity after 1 h, although functional recovery of respiration was complete within this time. Additional doses of the agents were administered at various times after recovery from the respiratory blockade. Following spontaneous restoration of ventilatory function, subsequent injections of the organophosphorus compounds failed to reinstate central respiratory paralysis, although they further depressed brainstem AChE levels. These data suggest that spontaneous recovery of central respiratory function after intoxication with Soman or Sarin may not be related to the return of AChE activity.

Physiology and pharmacology of nasal function and mucus secretion

Abstract The nose plays an important part in the normal physiological function of the body and is a key defense against airborne noxious influences. The ability of the nose to play these roles is dependent upon a normal nasal airway and healthy nasal mucosa. Most nasal diseases run a self-limited course, and injury resulting therefrom is quickly followed by a restoration of normal function. In the treatment of nasal symptoms the physician must carefully weigh the desire to alleviate the patients discomfort against the possibility of acutely or chronically impairing nasal function. Even a cursory examination of the literature reveals the paucity of reliable information not only on the relative effectiveness of most pharmacological agents employed in nasal disease, but also on their adverse effects upon nasal function. We now have a better understanding of nasal function which can serve as a guide to those seeking the discovery of improved nasal medications. We also have readily available tools for measuring some of the desired effects of drugs upon nasal function and some of the functions which might be injured. Rhinomanometry (Brown, 1967; Bridger and Proctor, 1970) and measurement of mucociliary function (Hill, 1957; Gosselin, 1961; Quinlan et al. , 1969; Dadaian, 1971; Sakakura et al. , 1973) can be carried out by intelligent investigators in most first class clinical environments. Climate chambers are available for testing the effects of environmental influences and for measuring the effect of therapeutic agents under controlled conditions (Proctor et al. , 1973a). We urge that appropriate studies be employed for weighing the relative usefulness of currently used drugs and for testing new ones prior to their release for public consumption. Clinical impression, upon which we must now to a large degree rely, should not be accepted in the future as adequate evidence supporting pharmacological therapy of nasal disease.

Single-Breath Deposition of Jet-Nebulized Saline Aerosol

A common method of inhalation of aerosols used in clinical research and in therapy is by single inspiratory breaths at unregulated inspiratory flow rates from a jet-type nebulizer. We have studied the effect of inspiratory flow rate on the regional deposition of such an orally inhaled aerosol when delivered to the human respiratory tract directly from a jet-type nebulizer by single inspiratory breaths. The aerosol, generated by a No.42 DeVilbiss jet nebulizer, was inhaled by mouth by three normal human subjects at flow rates between 13 and 165 1/min. At mean inspiratory flow rates ranging between 13 and 35 1/min, deposition of the radioaerosol was predominantly in the bronchopulmonary region (larynx and below) of the three subjects. Inhalation of the aerosol at flow rates above 48 1/min resulted in increasing oropharyngeal deposition (supralaryngeal). Oropharyngeal deposition of the aerosol, at all inspriatory flow rates, was greater than predicted by the Stokes number calculated using the inspiratory flo...