Researchers have previously studied the isotopic ratio of .sup.13 C/.sup.12 C in human breath. In these experiments, subjects were administered artificially labeled .sup.13 C substrates before the study began. For example, Lacroix, et al., in Stable Isotopes, Schmidt, et al., editors, pp. 393-398 (1982) studied glucose metabolism during exercise as measured by CO.sub.2 mass spectrometry after feeding .sup.13 C labeled glucose to the subjects. The disclosure of this article and of all other publications referred to herein are incorporated by reference as if fully set forth herein.
Similarly in Klein, et al., European Patent Application No. 253,927 (January 1988) the inventors discussed feeding .sup.13 C labeled urea to subjects in an attempt to detect the bacteria which cause ulcers. Urease activity in ulcer bacteria converts urea to carbon dioxide and ammonia. Breath samples were collected from the test subjects and analyzed for the presence of labelled isotope in exhaled carbon dioxide.
Jarvis, et al., 24 Medicine and Science in Sports and Exercise 320-326 (1992) discloses the effect of different food matrixes labeled with .sup.13 C on breath CO.sub.2 isotopic ratios during moderate exercise and Murphy, et al., 65 Archives of Disease in Childhood 574-578 (1990) discloses the use of isotopic ratios in breath CO.sub.2 to test for lipase activity in the human gut after feeding the subjects fat labeled with .sup.13 C.
U.S. Pat. No. 4,298,347 discusses a method for analyzing isotopic ratios in exhaled carbon dioxide when performing the above type of studies. The method involves a solvent and an organometallic compound that reacts with gaseous carbon dioxide and forms a soluble carbonyl compound which has a unique and well separated infrared spectral peak for the .sup.12 C and .sup.13 C or .sup.15 N:.sup.14 N products in the carbonyl frequency.
Schoeller, et al., 18 Ecology of Food and Nutrition 159-170 (1986) compares dietary isotopic ratios with the isotopic ratios in human plasma and hair. The article notes that the diet/tissue isotopic carbon ratio differences observed were small.
Gautier, et al., 74 Journal of Applied Physiology 133-138 (1993) studied the effect of the potent lypolysis inhibitor Acipimox by determining to what extent this affects the .sup.13 C:.sup.12 C ratio in expired air CO.sub.2 while the subject engaged in exercise. They concluded that if feeding experiments are done during exercise, a control should be run to correct for the effect of the exercise.
Researchers in the field often represent isotopic ratios as .delta..sup.13 C0/00=(R.sub.u /R.sub.s -1).times.1000 where R.sub.u and R.sub.s are the .sup.13 CO.sub.2 to .sup.12 CO.sub.2 ratios of the sample and belemnite from the Pee Dee Formation in South Carolina respectively.
Notwithstanding this art, we believe that no one else to date has used monitoring of .sup.13 C:.sup.12 C (or nitrogen stable isotope pairs) in isotopically unenriched subjects as a diagnostic tool.
USPTO Backgrounds
USPTO Backgrounds