Hypothermia protects brain function in acute carbon monoxide poisoning

The role of body temperature in the morbidity and mortality resulting from acute severe carbon monoxide (CO) poisoning (2400 ppm CO, 90 min) was investigated using an unanesthetized animal model. Modified Levine prepared female rats (left common carotid artery and jugular cannulated) displayed a lower rate of recovery period (4 hr) re-warming, and an increased mortality rate and behaviorally-assessed neurologic index (NI) compared to normal rats. This indicated their greater susceptibility to CO hypoxia, although the degree of CO-induced hypothermia was the same in both groups. The whole-body cooling of Levine rats to a similar extent prior to CO exposure increased somewhat the post-CO re-warming rate, and marginally decreased NI and mortality during CO exposure (in-CO). In contrast, maintenance of constant body temperature by external heating during CO exposure resulted in a negative post-CO re-warming rate and sharply increased NI and in-CO mortality. Normal euthermic rats were much less severely affected by CO. The results suggest that hypothermia, whether CO-induced or produced by prior cooling, provides measurable protection of brain function during acute severe CO poisoning, and that maintenance of body temperature increases in-CO mortality and interferes with ability to thermoregulate and increases NI in survivors.     

HEALTH STATUS AND HEALTH CARE IN RURAL AUSTRALIA: A CASE STUDY

Knowledge of the health status of, and patterns of health care service utilization by rural Australian communities, is scant. This deficiency limits attempts to formulate policies designed to bring about efficient, effective and equitable delivery of health care services. This article reports the results of a health interview survey conducted in the Wimmera region of Victoria during spring 1984. The results demonstrate not only that patterns of morbidity in rural areas differ from the Australian average, but also that the health status of rural dwellers is worse than that of most Australians. Evidence suggests that while accessibility is not the most significant determinant of utilization of health care services, distance from services does affect propensity to use them.     

Hearing loss and otitis media on Guam: impact of professional services

In less than two decades, there has been a dramatic reduction in the prevalence of otitis media and perforations among Guam's school-aged children. In addition, hearing loss due to chronic middle ear disease as a cause of disqualification from military service has dropped from a first rank order cause to next-to-last. However, there has been no reduction in the prevalence of otitis media in the preschool population. The reduction in chronic ear disease is the result of improved access to primary care, intensive hearing screening, wide availability of audiologic diagnostic and follow-up services, and comprehensive otologic care. It is essential that these services continue to be available to Guam's children to avoid a reversal of these dramatic gains. Attention must now focus on how to achieve similar gains for Micronesian children who remain restricted in their access to these resources.     

Conformationally restricted analogues of the muscarinic agent N-methyl-N-(1-methyl-4-pyrrolidino-2-butynyl)acetamide

Conformationally restricted analogues of the selective partial muscarinic agonist N-methyl-N-(1-methyl-4-pyrrolidino-2-butynyl)acetamide (BM 5; 2) were synthesized. The compounds were tested for muscarinic and antimuscarinic activity in the isolated guinea pig ileum and in intact mice. They were found to be moderately potent muscarinic antagonists or weak partial agonists. The new compounds were less potent than 2 in inhibiting (-)-[3H]-N-methylscopolamine binding in the rate cerebral cortex. Thus, structural modifications of 2 in which part of the amide moiety has been connected with the methyl group in the butynyl chain to form a five-membered ring decrease affinity and in most cases abolish efficacy.     

Positive end-expiratory pressure and the damaged right ventricle. An experimental open versus closed chest study

Hemodynamic changes after isolated impairment of right ventricular function (produced by increasing afterload by temporary banding of the pulmonary artery) were studied in 22 ventilated pigs during increased levels of positive end-expiratory pressure (4, 8, 12, and 16 cm H2O). In the open chest group, application of positive end-expiratory pressure produced only a slight decrease of cardiac index. After right ventricular damage a decrease of cardiac index of more than 25% occurred only when higher levels of positive end-expiratory pressure were applied. In contrast to the open chest group, the closed chest group showed more distinct cardiovascular responses after positive end-expiratory pressure. In the damaged right ventricle with a positive end-expiratory pressure of 16 cm H2O, right ventricular end-diastolic pressure increased more than 100%. With positive end-expiratory pressure, cardiac index decreased 34% before and 47% after right ventricular damage. We conclude that positive end-expiratory pressure induces a more pronounced decrease in cardiac index if right ventricular function is impaired. During open chest conditions with lower levels of positive end-expiratory pressure, these changes are only small, however, and probably irrelevant. During closed chest conditions, the hemodynamic changes are much more pronounced. High right ventricular end-diastolic pressures resulting from impaired right ventricular contractility as well as from high levels of positive end-expiratory pressure may have an impact on biventricular function and right ventricular coronary driving pressure.     

Pharmacological properties of fluphenazine-mustard, an irreversible calmodulin antagonist

We describe an improved synthesis and properties of fluphenazine-mustard, a potent phenothiazine having an alkylating chlorethylamine chain in its structure. The drug possesses anticalmodulin activity equivalent to the parent compound, but unlike fluphenazine dihydrochloride, the mustard derivative irreversibly antagonizes the ability of calmodulin to activate cyclic nucleotide phosphodiesterase. This property is partially calcium-dependent and can be overcome by coincubation with excess fluphenazine dihydrochloride. The compound irreversibly inactivated calmodulin when incubated with intact cells and caused single-stranded breakage of DNA. Fluphenazine-mustard possesses potent antiproliferative and cytotoxic properties against malignant cell lines that are likely to be mediated through both of these actions.