Practical and analytical aspects of using friend controls in case-control studies: experience from a case-control study of childhood cancer.

We report empirical data on the use of friend controls, specifically response rates, case-control concordance and analytical approaches. The data derive from a North American multi-institutional study of childhood cancer that was conducted in 2002-07 and that focused on paternal exposures. Case parents nominated friends as potential controls; up to three controls participated per case. For 137 (69%) of the 199 case families, at least one control parent participated. Of 374 potential controls contacted, 247 (66%) participated. Case fathers with controls were markedly more likely to be non-Hispanic White, college graduates and non-smokers compared with case fathers without controls. Odds ratios adjusted for demographic characteristics were generally similar but occasionally differed between analyses that included only members of matched sets and those that included all participants, i.e., controls and cases with and without controls. For demographic characteristics, simulations demonstrated that the observed concordance of cases and controls within matched sets exceeded that expected under random ascertainment, indicating probable overmatching. However, the observed concordance of smoking and other exposures was similar to the expectation under random ascertainment, suggesting little overmatching on exposures. Although not ideal, friend controls were convenient, had a reasonably high response rate and provided controls closely matched on race/ethnicity, education and age.

Nerve growth factor sensitivity is broadly distributed among myenteric neurons of the rat colon.

Nerve growth factor (NGF) acts on the two-receptor system of trkA and p75 to mediate neuroprotection and influence phenotype and function in the peripheral nervous system, but the effects of NGF on the enteric nervous system (ENS) are virtually unknown. To establish a basis for enteric responsiveness to NGF, we studied the presence and distribution of NGF-sensitive receptors in the myenteric neurons of the normal rat colon and examined their activation via trkA phosphorylation. Fluorescent immunocytochemistry on wholemounts showed that the two NGF receptors were abundantly present in the ENS, with 71% of all neurons positive for trkA and 78% for p75. More thanr 60% of the myenteric neurons expressed both receptors, and exogenous application of NGF resulted in trkA phosphorylation, evidence for high NGF sensitivity within the ENS. trkA was co-expressed with choline acetyltransferase (61% of trkA-positive neurons), neuronal nitric oxide synthase (22%), or calbindin (10%), suggesting widespread potential for NGF action. We conclude that functional receptors for NGF are widely distributed among the diverse enteric phenotypes and argue for a novel NGF-mediated regulatory system within the ENS.