Cortisol and ACTH exhibit circadian rhythmicity, peaking in the early morning. These peaks are associated with increased activity and alertness. We sought to determine whether self-reported daily rhythms predict outcome of a.m. and p.m. CRH challenge in elderly subjects. We surveyed 96 elderly subjects to determine daily rhythms in activity levels, mood, alertness, and performance. Seven healthy subjects were given a cumulative activity score reflecting propensity toward morningness or eveningness. Subjects underwent CRH challenge testing during the morning and evening hours of different days. Baseline plasma ACTH and cortisol concentrations were higher in the morning than in the evening and lower values were associated with lower activity scores (i.e., greater morningness). No trends were apparent between activity score and net hormone response or percent change in hormone concentration.

Adrenocorticotropic Hormone↗

PubMedDate not supplied

Metabolic oxidation phenotypes as markers for susceptibility to lung cancer.

That bronchial carcinoma is not an inevitable consequence of cigarette smoking has stimulated the search for host factors that might influence the susceptibility of the individual smoker. One plausible host factor would be a polymorphic gene controlling the metabolic oxidative activation of chemical carcinogens, giving rise to wide inter-subject variation in the generation of cancer-inducing and/or promoting species. Recently, three genetic polymorphisms of human metabolic oxidation have been demonstrated (as characterized by debrisoquine, mephenytoin and carbocysteine), with the metabolism of several substrates exhibiting the phenomenon. Debrisoquine 4-hydroxylation segregates into two human phenotypes, each comprising characteristic metabolic capability. We report here the frequency of debrisoquine 4-hydroxylation phenotypes in age-, sex- and smoking history-matched bronchial carcinoma and control patients. Cancer patients showed a preponderance of probable homozygous dominant extensive metabolizers (78.8%) with few recessive poor metabolizers (1.6%) compared with smoking controls (27.8% and 9.0% respectively). We conclude that the gene controlling debrisoquine 4-hydroxylation may be a host genetic determinant of susceptibility to lung cancer in smokers and that it represents a marker to assist in assessing individual risk.

Carcinoma, Bronchogenic↗