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In a recent issue of the ARCHIVES, Geschwind et al1 reported that the 14-3-3 protein test performed in different laboratories across the United States is not a sensitive test for the diagnosis of sporadic Creutzfeldt-Jakob disease (sCJD), in contrast with the results published by European centers. We agree with the authors and with Aksamit,2 in the accompanying editorial, that the lack of centralized laboratories and formal standardization for this test in the United States is the best but not the only explanation for this discrepancy. In our opinion, 2 points deserve further comment: the issue of handling samples and a possible bias in the population studied.
Our laboratory established the 14-3-3 protein test by immunoblot in 1996. Standardization was achieved through exchange of samples with other European laboratories3 - 4 and participation in technical workshops. The laboratory works as a private reference center in Spain and since 1997 as part of the surveillance system of CJD in Catalonia (Spain).5 Until June 2003, we analyzed 1396 samples of suspected sCJD cases. A definite sCJD diagnosis was obtained in 88 cases, and in 78 (89%) the 14-3-3 test result was positive. The specificity of the test was 85%. These figures were no different when the data were limited to cases related to the surveillance system (91% and 85%, respectively) and rule out the possibility that a bias in patient referral could play a role in the results. Samples were sent to our laboratory at room temperature. In addition, we performed the test in samples with positive findings after repeated freeze-thaw cycles or when kept at room temperature for several days without a loss of sensitivity. These observations strongly suggest that the handling of samples does not explain the discrepancy in the results of Geschwind and colleagues.
Our main concern about the low sensitivity of the test in the study of Geschwind et al1 is related to a possible bias in the population studied. The median disease duration of 8 months (range, 2-33 months; mean ± SD, 10.4 ± 7.5 months) contrasts with that of 4 months (range, 2-30 months; mean ± SD, 5.4 ± 5.4 months) in our series, similar to that found in other studies.6 - 7 In addition to the fact that genetic analysis was not conducted in the series by Geschwind and colleagues', a longer disease duration could suggest a genetic bias toward genotypes (heterozygosity at codon 129) in which the 14-3-3 protein test is less sensitive.7 On the other hand, in our study the frequency of genetic cases of apparent sCJD was about 5%, although most of them were associated with positive results on 14-3-3 protein tests.
Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature
Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal
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