Resident-centered MDR is an effective process using no additional resources that simultaneously improves quality of care while enhancing resident education and is associated with shortened length of stay.

We have studied a number of cell surface, enzyme, and protein markers in the human leukemic K562 cell line. We have confirmed previous observations that these cells accumulate human embryonic hemoglobins after exposure to hemin. In addition, our results demonstrated that these cells possess in their "uninduced" state i surface antigen, lactate dehydrogenase isoenzymes characteristic of embryonic or fetal erythroid cells, fetal and embryonic globin chains, and globin mRNAs.

We have recently described an in vitro clonal assay system for human megakaryocyte-progenitor cells or megakaryocytic colony-forming units (CFU-M). Serum specimens from patients with quantitative platelet disorders were screened for the capacity to alter in vitro megakaryocyte-colony formation. Serum from 11 patients with hypomegakaryocytic thrombocytopenia significantly enhanced the formation of CFU-M-derived colonies (200 to 1840 per cent). Neither serum from eight patients with thrombocytopenia and normal or increased numbers of marrow megakaryocytes nor serum from 11 patients with thrombocytosis altered colony formation. This stimulatory activity has been termed megakaryocytic-colony-stimulating activity (Meg-CSA). The number of megakaryocytic colonies formed was directly proportional to the quantity of stimulatory serum added. Meg-CSA levels appeared to be inversely related to marrow megakaryocyte numbers. The variations in Meg-CSA levels that were detected in different disease states suggest that alterations in the production of this stem-cell regulator have physiologic importance.

OBJECTIVE:Although hospitalists have been shown to improve both financial and educational outcomes, their ability to manage dual roles as clinicians and educators has been infrequently demonstrated, particularly in the community setting where large numbers of residents train. We evaluated the impact of hospitalists on financial and educational outcomes at a midsized community teaching hospital 1 year after implementation. DESIGN:Two hospitalist clinician educators ( HCEs) were hired to provide inpatient medical care while participating in resident education. Length of stay and cost per case data were calculated for all patients admitted to the hospitalist service during their first year and compared with patients admitted to private physicians. The hospitalists' top 11 discharge diagnoses were individually assessed. For the same time period, categorical medicine residents ( N = 36) were given an anonymous written survey to assess the HCEs' impact on resident education and service. RESULTS:Resource consumption: length of stay was reduced by 20.8% and total cost per case was reduced by 18.4% comparing the HCEs with community-based physicians. Reductions in both length of stay and cost per case were noted for 8 of the 11 most common discharge diagnoses. Resident survey: over 75% of residents responded, with all noting improvement in the quality of attending rounds, bedside teaching, and the overall inpatient experience. Residents' roles as teachers and team leaders were largely unchanged. A driving force behind the expansion of the hospitalist movement is the potential to deliver high-quality medical care while decreasing inpatient costs and improving efficiency. Several institutions have demonstrated that both length of stay (LOS) and cost per case (C/C) have been reduced through the use of hospitalists. CONCLUSION:1-6 On average, hospitalists have been reported to reduce LOS by 16.6% and C/C by 13.4%. 1 Such decreases have been shown in both academic 2,3 and community-based institutions. [4][5][6] Though economic forces ultimately drive the utilization of hospitalists, other outcomes, such as the benefit of hospitalists on the medical education of internal medicine residents and medical students, have been explored to a limited extent. 7 In one large university medical center, residents expressed satisfaction with the teaching provided by hospitalists and reported that it was equivalent and often superior to that of traditional ward attendings. 2 In fact, these residents requested that hospitalists be a part of all of their future inpatient ward rotations. Another university medical center found that the presence of hospitalists improved the quality of attending rounds, increased the emphasis on resident education during inpatient rotations, and enhanced residents' overall learning experience. 8Despite the fact that hospitalists often serve in dual roles as clinicians and educators, there are few data on their ability to effectively manage these roles simultaneously. For academic community-based teaching hospital...

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Anagrelide is a new therapeutic compound recently demonstrated to have a rapid and selective thrombocytopenic effect in humans. The effects of anagrelide were evaluated in plasma clot and liquid suspension cultures of optimally stimulated normal human peripheral blood megakaryocyte progenitors in order to determine the mechanism of its thrombocytopenic activity. In plasma clot cultures, at clinically relevant, therapeutic concentrations (5 to 50 ng/mL), anagrelide exerted no significant inhibitory effect on megakaryocyte colony numbers or colony size. Only at anagrelide concentrations of 10 to 500 times therapeutic doses did anagrelide inhibit megakaryocyte colony development: an anagrelide concentration of 5 micrograms/mL reduced colony numbers by 57% and colony size by 31%. In contrast, lower, therapeutic anagrelide concentrations exerted profound effects in liquid culture on megakaryocyte cytoplasmic maturation, size, and DNA content. When present for the entire 12-day culture duration, anagrelide induced left- shifted megakaryocyte maturation and reduced both megakaryocyte ploidy and megakaryocyte diameter. Anagrelide, at concentrations of 5 to 50 ng/mL, shifted the modal cultured megakaryocyte morphologic stage from III to II, reduced the model ploidy value from 16N to 8N, and decreased the mean megakaryocyte diameter by up to 22%, from 27.6 microns to 21.6 microns. Megakaryocyte diameter was significantly reduced in most instances, even when analyzed as a function of morphologic stage. When anagrelide was added to the cultures after 6- and 9-day delays (during the final 6 and 3 days, respectively, of culture), similar inhibitory effects on megakaryocyte maturation stage and ploidy distribution were observed. However, the magnitude of the left-shift in ploidy appeared to be less as the duration of anagrelide exposure was reduced. Conversely, megakaryocyte diameter was not significantly affected by the shorter 3- and 6-day anagrelide exposures. These data indicate that therapeutic concentrations of anagrelide influence primarily the postmitotic phase of megakaryocyte development, decreasing platelet production by reducing megakaryocyte size and ploidy, as well as by disrupting full megakaryocyte maturation. Inhibition of megakaryocyte diameter appears to require more prolonged anagrelide exposure than inhibition of maturation stage and ploidy. The molecular mechanisms responsible for the inhibitory effects of anagrelide on megakaryocytopoiesis remain to be defined.

The possible pathogenetic mechanisms responsible for the production of acquired amegakaryocytic thrombocytopenic purpura (AATP) were investigated in a group of patients with this disorder. Absence of megakaryocytes and small platelet glycoprotein-bearing mononuclear cells, as determined by immunochemical staining of patient marrows with an antisera to platelet glycoproteins, suggested that the defect in AATP occurs in an early progenitor cell of the megakaryocytic lineage. Using an in vitro clonal assay system for negakaryocytic progenitor cells or megakaryocyte colony-forming units (CFU-M), the proliferative capacity of AATP marrow cells was then assessed. Bone marrow cells from three of four patients formed virtually no megakaryocyte colonies, suggesting that in these individuals the AATP was due to an intrinsic defect in the CFU-M. Bone marrow cells from an additional patient, however, formed 12% of the normal numbers of colonies, providing evidence for at least partial integrity of the CFU-M compartment in this patient. Serum specimens from all six patients were screened for their capacity to alter in vitro megakaryocyte colony formation. Five of six sera enhanced colony formation in a stepwise fashion, demonstrating appropriately elevated levels of megakaryocyte colony- stimulating activity. The serum of the patient with partial integrity of the CFU-M compartment, however, stimulated colony formation only at low concentrations. At higher concentrations, this patient's serum actually inhibited the number of colonies cloned, suggesting the presence of a humoral inhibitor to CFU-M. Serum samples from all patients were further screened for such humoral inhibitors of megakaryocyte colony formation using a cytotoxicity assay. The patient whose serum was inhibitory to CFU-M at high concentrations was indeed found to have a complement-dependent serum IgG inhibitor that was cytotoxic to allogeneic and autologous marrow CFU-M but did not alter erythroid colony formation. These-studies suggest that AATP can be due to at least two mechanisms: either an intrinsic effect at the level of the CFU-M or a circulating cytotoxic autoantibody directed against the CFU-M.

Plasminogen activator inhibitor-1 (PAI-1) is present in the platelet ^-granule and is released on platelet activation. Platelet PAI-1 could either be synthesized by the megakaryocyte or taken up from the plasma. In this report we confirm the presence of PAI-1 protein in human megakaryocytes by Western blot analysis and show its synthesis in guinea pig megakaryocytes by metabolic labeling. We document the presence of PAI-1 mRNA in human platelets and show a 3-kb mRNA species on Northern blot analysis of guinea pig megakaryocytes. Neither untreated CHRF-288 cells, a megakaryoyblastic cell line, nor human erythroleukemia (