A more powerful robust test for linkage is developed from the methodology of Haseman and Elston [Behav Genet 2(1):3-19, 1972]. This new robust test uses weighted least-squares (WLS) methods to detect linkage between a quantitative trait and a polymorphic marker. For comparison, the characteristics of a test for linakge that uses known trait genotypes for the parents are also studied. Sample sizes needed to detect linkage, calculated using asymptotic results, are compared for 1) the usual Haseman-Elston method, 2) the WLS method, and 3) the method that uses parental trait genotype data. The WLS method needs at most twice the number of sib pairs as does the method that uses information on the trait genotypes of the parents. The small sample properties of the Haseman-Elston (H-E) and WLS tests are investigated by simulation. The power calculations for the H-E method are found to be accurate. The power of the WLS method is overestimated when fewer than 300 sib pairs are studied, but the WLS method is nonetheless more powerful than the usual H-E method. In samples of fewer than 300 sib pairs, the WLS test tends to be anticonservative. Treating all sib pairs from sibships of size 3 or 5 as independent does not increase the significance of the tests.

Detection of anaerobic threshold (AT) requires either invasive techniques or expensive gas analyzers and somewhat complicated procedures. The purpose of this study was to determine if ventilatory frequency (f) could be used to detect AT. Thirteen (seven females) healthy, non-smoking, physically active adults (21-44 years) volunteered to perform progressive cycle exercise. A protocol of either 22.5- or 45-W increments every 2 min was used according to the subject's weight and fitness to assure steady state. Expiratory gas was measured using a computerized breath-by-breath system. Mean values of oxygen uptake (VO2, 1.min-1), ventilation (VE, 1.min-1), and f(br.min-1) were calculated each min. Peak VO2 ranged from 24.8 to 58.9 ml.kg-1.min with a group mean (+/- SD) of 45.1 +/- 11.6 ml.kg-1.min. Mean (+/- SD) VO2 at AT, as determined by disproportionate increase of VE, was 2.11 +/- 0.57 1.min-1. Mean (+/- SD) VO2 at the point of disproportionate increase of f was 2.09 +/- 0.58 1.min-1. A significant (P less than 0.05) correlation (r = 0.834) was found between the point of disproportionate increase in f and that of VE for individual data. A Student's t test indicated there was no significant difference in mean VO2 at AT. It was concluded that AT could be detected by f in healthy, physically active adults, thus providing a simplified and less expensive alternative method. This finding may have implications with regard to establishing and monitoring exercise intensity.

RO-07-0582 toxicity studies were performed in 12 patients for a total of 16 assays. Single and multifraction dose schedules were used, and drug concentrations in solid tumor tissue, cerebrospinal fluid, and blood (at 14 to 24 hr.) were established. A severe peripheral neuropathy occurred in 1 patient on the multifraction regimen when the total dosage reached 24 g. Drug absorption and concentration in the blood do not significantly differ from that of metronidazole. Maximum blood levels were reached at from 2 to 4 hr., and several days subsequent to administration had stabilized to levels only slightly above control levels.

Serum dopamine-beta-hydroxylase (DBH) levels and 30 polymorphic markers were determined on 178 individuals of the HGAR 29 family, ascertained through six probands who had clinical and electrocardiographic evidence of myocardial infarction. Individuals in this pedigree with a history of heart attack had significantly lower levels of DBH, but this difference was partly confounded with age differences. Pedigree segregation analysis showed evidence of a codominant gene for DBH segregating in the family. Linkage analysis between the putative DBH locus and 30 polymorphic marker loci, assuming a codominant model, yielded a largest lod score of 0.53, with ABO at 20% recombination. Adding this to the lod scores obtained by Elston et al [1979] and Goldin et al [1982], we obtain combined lod scores of 2.49 and 2.50 at 0.0 and 10% recombination respectively.

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