Using automated pharmacy records to assess the management of tuberculosis.

We used automated pharmacy dispensing data to characterize tuberculosis (TB) management for 45 health maintenance organization (HMO) members. Pharmacy records distinguished patients treated in HMOs from those treated elsewhere. For cases treated in HMOs, they provided useful information about appropriateness of prescribed regimens and adherence to therapy.

Supplementing tuberculosis surveillance with automated data from health maintenance organizations.

Data collected by health maintenance organizations (HMOs), which provide care for an increasing number of persons with tuberculosis (TB), may be used to complement traditional TB surveillance. We evaluated the ability of HMO-based surveillance to contribute to overall TB reporting through the use of routinely collected automated data for approximately 350,000 HMO members. During approximately 1.5 million person-years, 45 incident cases were identified in either HMO or public health department records. Eight (18%) confirmed cases had not been identified by the public health department. The most useful screening criterion (sensitivity of 89% and predictive value positive of 30%) was dispensing of two or more TB drugs. Pharmacy dispensing information routinely collected by many HMOs appears to be a useful adjunct to traditional TB surveillance, particularly for identifying cases without positive microbiologic results that may be missed by traditional public health surveillance methods.

Energetically unfavorable interactions among the zinc fingers of transcription factor IIIA when bound to the 5 S rRNA gene.

Xenopus transcription factor IIIA (TFIIIA) binds to over 50 base pairs in the internal control region of the 5 S rRNA gene, yet the binding energy for this interaction (DeltaG0 = -12.8 kcal/mol) is no greater than that exhibited by many proteins that occupy much smaller DNA targets. Despite considerable study, the distribution of the DNA binding energy among the various zinc fingers of TFIIIA remains poorly understood. By analyzing TFIIIA mutants with disruptions of individual zinc fingers, we have previously shown that each finger contributes favorably to binding (Del Rio, S., Menezes, S. R., and Setzer, D. R. (1993) J. Mol. Biol. 233, 567-579). Those results also suggested, however, that simultaneous binding by all nine zinc fingers of TFIIIA may involve a substantial energetic cost. Using complementary N- and C-terminal fragments and full-length proteins containing pairs of disrupted fingers, we now show that energetic interference indeed occurs between zinc fingers when TFIIIA binds to the 5 S rRNA gene and that the greatest interference occurs between fingers at opposite ends of the protein in the TFIIIA.5 S rRNA gene complex. Some, but not all, of the thermodynamically unfavorable strain in the TFIIIA.5 S rRNA gene complex may be derived from bending of the DNA that is necessary to accommodate simultaneous binding by all nine zinc fingers of TFIIIA. The energetics of DNA binding by TFIIIA thus emerges as a compromise between individual favorable contacts of importance along the length of the internal control region and long range strain or distortion in the protein, the 5 S rRNA gene, or both that is necessary to accommodate the various local interactions.