James L. Frost

The effect of ouabain on tension in isolated respiratory tract smooth muscle of humans and other species

1 The Na+, K+‐pump has been implicated in animal models of airway hyperreactivity. We examined the effects of inhibiting the Na+, K+‐pump and Na+, Ca2+‐exchange on isometric tone of isolated trachealis from humans and other species. 2 In preparations from 5 out of 9 humans, strong spontaneous contractions (36–48 h−1; up to 1.8 g) developed within 25 min. 3 Ouabain (10−7‐10−5 m) caused an immediate and sustained contraction. This response was not blocked by atropine, diphenhydramine, or cimetidine. 4 Contractions were also elicited when the normal physiological solution was changed to a K+‐free solution, a procedure which inhibits the Na+, K+‐pump, and in reduced (15 mm) Na+ solution, which inhibits Na+, Ca2+ exchange. 5 In preparations of dog and guinea‐pig isolated trachea, ouabain (10−5 m) caused a multiphasic response; in the rabbit, ouabain was without effect. K+‐free solution was without effect in the dog preparations and produced relaxation of the guinea‐pig trachea. Guinea‐pig tracheae responded to a low Na+ solution with a strong contraction. 6 Our findings indicate that: (a) human airway smooth muscle may be a spontaneously contracting muscle, at least in vitro, (b) a prolonged contraction to ouabain is unique for the human airway smooth muscle among the animals tested, as is the contraction in a K+‐free medium, and (c) the contractile response does not involve acetylcholine or histamine release, but may involve a Na+, Ca2+‐exchange mechanism. These results suggest that the level of Na+, K+‐pump activity could play a role in determining the degree of bronchomotor tone in humans.

Suicide and unintentional poisoning mortality trends in the United States, 1987-2006: two unrelated phenomena?

BackgroundTwo counter trends in injury mortality have been separately reported in the US in recent times - a declining suicide rate and a rapidly rising unintentional poisoning mortality rate. Poisoning suicides are especially difficult to detect, and injury of undetermined intent is the underlying cause-of-death category most likely to reflect this difficulty. We compare suicide and poisoning mortality trends over two decades in a preliminary assessment of their independence and implications for suicide misclassification.MethodsDescription of overall and gender- and age-specific trends using national mortality data from WISQARS, the Web-based Injury Statistics Query and Reporting System, maintained by the Centers for Disease Control and Prevention (CDC). Subjects were the 936,633 residents dying in the 50 states and the District of Columbia between 1987 and 2006 whose underlying cause of death was classified as suicide, unintentional poisoning, or injury mortality of undetermined intent.ResultsThe official US suicide rate declined 18% between 1987 and 2000, from 12.71 to 10.43 deaths per 100,000 population. It then increased to 11.15 deaths per 100,000 by 2006, a 7% rise. By contrast to these much smaller rate changes for suicide, the unintentional poisoning mortality rate rose more than fourfold between 1987 and 2006, from 2.19 to 9.22 deaths per 100,000. Only the population aged 65 years and older showed a sustained decline in the suicide rate over the entire observation period. Consistently highest in gender-age comparisons, the elderly male rate declined by 35%. The elderly female rate declined by 43%. Unlike rate trends for the non-elderly, both declines appeared independent of corresponding mortality trends for unintentional poisoning and poisoning of undetermined intent. The elderly also deviated from younger counterparts by having a smaller proportion of their injury deaths of undetermined intent classified as poisoning. Poisoning manifested as a less common method of suicide for this group than other decedents, except for those aged 15-24 years. Although remaining low, the undetermined poisoning mortality rate increased over the observation period.ConclusionsThe official decline in the suicide rate between 1987 and 2000 may have been a partial artifact of misclassification of non-elderly suicides within unintentional poisoning mortality. We recommend in-depth national, regional, and local population-based research investigations of the poisoning-suicide nexus, and endorse calls for widening the scope of the definition of suicide and evaluation of its risk factors.

Sudden, Unexpected Death in a 5-Year-Old Boy with an Unusual Primary Intracranial Neoplasm: Ganglioglioma of the Medulla

This report documents sudden, unexpected death in a 5-year-old boy from a ganglioglioma of the medulla. Gangliogliomas are rare, primary brain tumors that are encountered predominantly in childhood. We are unaware of any previous report of a similar case.