The marrow cell continuum: stochastic determinism.

Traditional models of hematopoiesis have been hierarchical in nature. Over the past 10 years, we have developed data indicating that hematopoiesis is regulated in a continuum with deterministic and stochastic components. We have shown that the most primitive stem cells, as represented by lineage negative rhodamine(low) Hoechst(low) murine marrow cells are continuously or intermittently cycling as determined by in vivo BrdU labeling. When marrow stem cells are induced to transit cell cycle by in vitro exposure to cytokines, either IL-3, IL-6, IL-11, and steel factor or thrombopoietin, FLT3 ligand, and steel factor, they progress through cycle in a highly synchronized fashion. We have determined that when the stem cells progress through a cytokine stimulated cell cycle the homing, engraftment, adhesion protein, global gene expression, and hematopoietic differentiation phenotypes all change in a reversible fashion. This has led to the continuum model, in which, with cycle transit, chromatin is continually changing altering open transcription areas and providing a continually changing landscape of transcriptional opportunity. More recently, we have extended the changing differentiation profiles to differentiation into lung cells and found that non-hematopoietic differentiation also shows cycle related reversibly modulation. These observations all together support a continuum model of stem cell regulation in which the phenotype of the marrow stem cells is continually and reversibly changing over time.

End-of-life care in medical textbooks.

Improvement in end-of-life care has become a demand of the public and a priority for health care professionals. Medical textbooks could support this improvement by functioning as educational resources and as reference material. In this paper, four widely used general medical textbooks are assessed for their coverage of nine content domains for 12 illnesses that often cause death; each domain in each disease and in each text was graded for presence and helpfulness of advice. Helpful information was rare, and only prognostication and medical treatments to alter the course of the disease were usually mentioned. Harrison's Textbook of Medicine, The Merck Manual, and Scientific American Medicine often mentioned at least a few of the domains in each disease, although not often in a way that would guide a clinician. Manual of Medical Therapeutics (The Washington Manual) includes little information about end-of-life care. Improvement seems possible. Short additions of information on end-of-life care would probably be effective. Many chapters discussed at length certain topics that are clearly optional; other textbooks addressed these topics only briefly. When dealing with end-of-life care, physicians should seek guidance from other sources and textbook authors and editors should improve the utility and completeness of their texts.