A method for measuring DNA synthesis and, thus, cell proliferation, in vivo is presented. The technique consists of administering [6,6-2 H 2 ]Glc or [U-13 C]Glc, isolating genomic DNA, hydrolyzing enzymatically to free deoxyribonucleosides, and derivatizing for GC-MS analysis of dA or dG isotopic enrichments, or both. Comparison of dA or dG to extracellular Glc enrichment (with a correction for intracellular dilution) reveals the fraction of newly synthesized DNA, by application of the precursor-product relationship. Thus, the technique differs from the widely used [ 3 H]thymidine or BrdUrd techniques in that the de novo nucleotide synthesis pathway, rather than the nucleoside salvage pathway, is used to label DNA; the deoxyribose rather than the base moiety is labeled; purine rather than pyrimidine deoxyribonucleosides are analyzed; and stable isotopes rather than radioisotopes are used. The method is applied here in vitro to the growth of HepG 2 and H 9 cells in culture; in animals to proliferation of intestinal epithelium, thymus, and liver; and in humans to granulocyte turnover in blood. In all instances, measured cell proliferation kinetics were consistent with expected or independently measured kinetics. The method has several advantages over previously available techniques for measuring cell turnover, involves no radioactivity or potentially toxic metabolites, and is suitable for use in humans. The availability of a reliable and safe method for measuring cell proliferation in humans opens up a number of fundamental questions to direct experimental testing, including basic problems related to cancer, AIDS, and other pathologic states.Control of cell proliferation is important in all multicellular organisms. A number of pathologic processes, including cancer and AIDS (1-3), are characterized by failure of the normal regulation of cell turnover. Measurement of the in vivo turnover of cells would therefore have wide application, if a method were available. Presently, direct and indirect techniques for measuring cell proliferation or destruction exist, but both types are flawed.Direct measurement generally involves the incorporation of a labeled nucleoside into genomic DNA. Examples include the tritiated thymidine ([ 3 H]dT) and BrdUrd methods (4, 5). These techniques are of limited applicability in humans, however, because of radiation-induced DNA damage with the former (6) and toxicities of nucleoside analogues (7) with the latter.Indirect methods also have been used in specific cases. Recent interest in CD4 ϩ T lymphocyte turnover in AIDS, for example, has been stimulated by using indirect estimates of T cell prolif-

MMT is associated with improved outcomes for individuals and pregnant women with opioid use disorders. MMT should be a covered service available to all individuals.

BMT is associated with improved outcomes compared with placebo for individuals and pregnant women with opioid use disorders. BMT should be considered for inclusion as a covered benefit.

No abstract

Current trends show that the proportion of nursing home admissions with mental illness, in particular depression, has overtaken the proportion with dementia. These changes may be related to increased recognition of depression, availability of alternatives to nursing homes for persons with dementia, and increased specialization among nursing homes in the care of postacute, rehabilitation residents. In light of these trends, it is critical to ensure that nursing homes have resources to adequately treat residents with mental illness to facilitate community reintegration.