Accurate assessment of preoperative Hb levels, better estimation of perioperative blood loss, efficient use of autologous blood, adherence to transfusion guidelines, and pharmacologic alternatives contribute to effective and comprehensive blood and anemia management.
This randomized comparison revealed that EPO significantly increases most of the hematologic effect produced by G-CSF administration after chemotherapy. This biologic property of EPO translated in vivo into a global improvement of patients' hematologic status.
OBJECTIVE -To clarify the pathogenesis of diabetes associated with mutations of the hemochromatosis (HFE) gene, 17 carriers, 9 normal glucose tolerant (NGT) and 8 diabetic, were evaluated in an interventional trial.
RESEARCH DESIGN AND METHODS-At enrollment and after a 2-year bloodletting period, euglycemic-hyperinsulinemic clamp, oral glucose tolerance test (OGTT), liver histology (nonalcoholic fatty liver disease activity score [NAS]), and liver iron content (LIC) were assessed.RESULTS -NGT subjects had significantly higher baseline insulin sensitivity (P Յ 0.001), secretion, and insulinogenic index (calculated from the OGTT) (P Յ 0.0001 for both) and lower LIC (P ϭ 0.004) and NAS (P ϭ 0.02) than diabetic patients. Baseline LIC correlated negatively with insulin secretion (NGT r 0 ϭ Ϫ0.676, P Յ 0.0001; diabetes r 0 ϭ Ϫ0.589, P ϭ 0.02) and insulin sensitivity (M value) (NGT r 0 ϭ Ϫ0.597, P ϭ 0.009; diabetes r 0 ϭ Ϫ0.535, P ϭ 0.03) and positively with NAS (diabetes r 0 ϭ 0.649, P ϭ 0.007) and triglycerides (NGT r 0 ϭ 0.563, P ϭ 0.015). At month 24, circulating iron was reduced by 179 Ϯ 26% in NGT and 284 Ϯ 54% in diabetic subjects. Insulin secretion (NGT 20 Ϯ 4%; diabetes 33 Ϯ 7%) and insulin sensitivity (NGT 25 Ϯ 5%; diabetes 18 Ϯ 3%) increased. LIC decreased in both groups (NGT 126 Ϯ 42%; diabetes 61 Ϯ 13%), and NAS ameliorated (NGT 65.1 Ϯ 6.5 vs. 38.1 Ϯ 6.83; P Յ 0.0001; diabetes 2.1 Ϯ 10.7 vs. 69.9 Ϯ 10; P Յ 0.0001).CONCLUSIONS -Iron depletion ameliorates insulin secretion and sensitivity in NGT and diabetic carriers of HFE gene mutations. This amelioration occurs in parallel with decreased LIC and improved NAS. These results justify glucose tolerance testing and prophylactic iron depletion in asymptomatic carriers as well.
Summary. A subset of circulating CD34 cells was found to express CD105 antigen. Sorting experiments showed that most granulocyte±macrophage colony-forming units (GM-CFU) and burst-forming units ± erythroid (BFU-E) were retained in the CD34/CD105À fraction, whereas rare GM-CFU/BFU-E were generated from CD34/CD105 cells. Megakaryocytic aggregates were entirely retained in the CD34/CD105 fraction. Neutralizing doses of an anti-TGF-b1 antibody demonstrated CD34/CD105 cells capable of colony-forming activity without any signi®cant effect on CD34/CD105À cells. Cloning of secondary colonies revealed that CD34/CD105 cells had a signi®cantly higher secondary cloning ef®ciency than CD34/CD105À cells. CD34/CD105 cells had a signi®cantly higher long-term culture-initiating cell (LTC-IC) frequency than CD34/CD105À cells. Kinetic analysis showed that 75% of CD34/CD105 cells consisted of DNA 2n G0Ki-67À cells whereas 82% of CD34/CD105À were DNA 2n G1Ki-67 cells, and this latter subset showed a RNA content consistently higher than CD34/CD105 cells. CD34/ CD105 progenitors were CD25, whereas CD34/ CD105À contained a small CD25 subset. Three-colour analysis of bone marrow and cord blood CD34 cells demonstrated that all the CD34/CD38 low/À primitive precursors were contained in CD34/CD105 cells. Extensive characterization of these CD105 precursors indicated that they have biological properties associated with primitive haematopoietic precursors.
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