Experiences of the first 493 unrelated marrow donors in the National Marrow Donor Program

More than 410,000 people participated in the National Marrow Donor Program (NMDP) as of October 1, 1991, and more than 850 volunteers had donated marrow. While the incidence of serious morbidity as a result of bone marrow donation is rare, the incidence of lesser complications and the long-term consequences of marrow donation are not known. To determine the incidence of donor complications and measure the recovery time of volunteer, unrelated marrow donors, we analyzed the results of surveys of the first 493 persons who donated marrow through the NMDP. The marrows were collected at 42 centers. The median age of the donors was 37.9 years (range 19.1 to 55.6 years). The median volume of marrow collected was 1,050 mL (range 180 to 2,983 mL). Autologous red blood cells were transfused to 89.8% (439) of donors but only 0.6% (3) of donors received allogeneic blood. Acute complications related to the collection procedure occurred in 5.9% of donors; but a serious complication, apnea during anesthesia, occurred in only one donor. When donors were questioned approximately 2 days following discharge from their hospitalization, most donors described symptoms related to the collection; 74.8% experienced tiredness, 67.8% experienced pain at the marrow collection site, and 51.6% of the donors experienced low back pain. Donors were surveyed repeatedly until they felt that they had recovered completely. Mean recovery time was 15.8 days; however, 42 (10%) donors felt that it took them > or = 30 days to recover fully. The duration of the marrow collection procedure and duration of anesthesia both positively correlated with donor pain and/or fatigue following the collection; but the duration of the collection procedure had the highest correlation with post-collection pain and fatigue. The volume of marrow collected per unit of donor weight was more weakly correlated with donor pain and/or fatigue than the anesthesia and collection times. When multivariate analysis was used to analyze the correlation between donor recovery time and these variables, only the duration of the collection was found to correlate significantly with donor recovery time (P = .001). This analysis demonstrates that marrow donation is well tolerated with few complications. To decrease further the incidence of donor discomfort and recovery time following donation, the duration of the collection procedure, and probably the duration of anesthesia, and the volume of marrow collected, should be kept to a minimum.     

Differentiation state and responses to hematopoietic growth factors of murine myeloid cells transformed by myb

Murine hematopoietic cells can be transformed in vitro by recombinant retroviruses that express the myb oncogene, and hematopoietic growth factor (HGF)-dependent myeloid cell lines can be derived from these transformed primary cells. In this study, the differentiation state and responses of myb-transformed hematopoietic cells (MTHCs) have been investigated. We find that MTHCs exhibit properties of early myeloid progenitors including synergistic responses to combinations of HGFs and expression of certain surface markers. As reported previously, MTHCs respond well to granulocyte-macrophage colony-stimulating factor (GM- CSF) but can also respond to interleukin-3 (IL-3); the response to the latter factor depends on the mouse strain from which the cells are derived. Although these single factors stimulate MTHCs, combinations of these factors with colony-stimulating factor-1 (CSF-1 or M-CSF) or Steel factor (SLF or SCF) act synergistically to promote colony formation. The surface markers expressed by MTHCs include both granulocyte-macrophage lineage specific antigens Gr-1, 7/4, F4/80, and Mac-1, as well as two antigens found on early progenitors and stem cells--Thy-1 and Sca-1 (Ly6E). Expression of the latter markers is often heterogeneous and can be modulated by the growth factors to which the cells are exposed. Finally, we show that monocytic differentiation of MTHCs can be induced by exposure to tumor necrosis factor (TNF alpha). Taken together, these results suggest that MTHCs will be a useful model for studying HGF/cytokine responses in both proliferation and differentiation.     

Changes in peripheral blood CD5 (Bla) B-cell populations and autoantibodies following blood transfusion

BACKGROUND: CD5 B cells and the natural autoantibodies they produce play a role in antigen presentation, tolerance induction, and maintenance of an idiotypic immune network. The effects of transfusion on autoantibodies and peripheral blood CD5 B cells were studied. STUDY DESIGN AND METHODS: Eight previously transfused patients with sickle cell anemia and five patients who underwent orthopedic surgical procedures with transfusion were enrolled in the study. Patients in both groups received 1 to 2 units of allogeneic packed red cells. Ten untransfused healthy adults and five patients who underwent orthopedic surgery without transfusion were enrolled as controls. Peripheral blood CD5 B cells, serum levels of IgM, antinuclear antibodies, rheumatoid factor, and anticardiolipin IgM were quantitated either at the beginning of the study (baseline sample), before transfusion, or before surgery and either at 1-, 2-, 4-, 6-, and 8-week intervals after transfusion, after surgery, or after the baseline sample was obtained. RESULTS: IgM levels and the absolute number of B cells that coexpressed CD5 rose to twice pretransfusion levels in six of eight transfused sickle cell anemia patients and in four of five transfused orthopedic surgery patients. No comparable increases in CD5 B cells were noted in untransfused controls. Preexisting rheumatoid factor and antinuclear antibody levels increased in four of five transfused orthopedic surgery patients. One sickle cell anemia patient developed anti-Fya despite receiving Fya-negative blood. Increasing titers of anti-Fya paralleled the increases in IgM and CD5 B cells after transfusion. One patient who developed a positive direct antiglobulin test after transfusion had large increases in serum anticardiolipin IgM. Anticardiolipin IgM was subsequently eluted from direct antiglobulin test-positive red cells obtained after transfusion. Antibodies with anti-Fya-like activity and anticardiolipin IgM were produced in vitro by CD5 B cells and not by conventional CD5-negative B cells. CONCLUSION: An association was found between transfusion-induced increases in CD5 B cells and increased autoantibody production. These data may have implications for immunologic intervention to prevent the induction of red cell antibodies and other changes in the immune system caused by exposure to foreign antigens via blood transfusion.     

Momentarily stuck in the foramen ovale.

An 80-year-old woman was admitted for a diagnosis of severe pulmonary embolism. A large serpentine thrombus stuck in a patent foramen ovale (PFO) completely resolved without the patient experiencing any manifestation. The right renal artery was the final destination. Thromboaspiration was unsuccessful. Three months later, the patient was diagnosed with a malignant melanoma and metastatic dissemination.     

Dysglycemias in pregnancy: from diagnosis to treatment. Brazilian consensus statement

There is an urgent need to find consensus on screening, diagnosing and treating all degrees of DYSGLYCEMIA that may occur during pregnancies in Brazil, considering that many cases of DYSGLYCEMIA in pregnant women are currently not diagnosed, leading to maternal and fetal complications. For this reason the Brazilian Diabetes Society (SBD) and the Brazilian Federation of Gynecology and Obstetrics Societies (FEBRASGO), got together to introduce this proposal. We present here a joint consensus regarding the standardization of clinical management for pregnant women with any degree of Dysglycemia, on the basis of current information, to improve medical assistance and to avoid related complications of Dysglycemia in pregnancy to the mother and the fetus. This consensus aims to standardize the diagnosis among general practitioners, endocrinologists and obstetricians allowing the dissemination of information in basic health units, public and private services, that are responsible for screening, diagnosing and treating disglycemic pregnant patients.     

Neochordal repair of a double orifice mitral valve

Native double-orifice mitral valve is an exceedingly rare valvular abnormality. A 77-year-old patient was referred for a severe mitral regurgitation, and a double-orifice mitral valve with a central fibrous bridge was unexpectedly found. A flail anterior leaflet with 2 ruptured chordae was observed on the anterolateral mitral valve orifice, the leaflets on the posterior valve orifice were normally thin. Mitral valve repair was successfully performed with replacement of the 2 torn chordae by two 4/0 expanded polytetrafluoroethylene neochordae. We accordingly suggest that current mitral valve repair techniques remained a valuable option, even on central bridge double-orifice mitral valve regurgitation.     

Enabling a robust scalable manufacturing process for therapeutic exosomes through oncogenic immortalization of human ESC-derived MSCs

Background  

Exosomes or secreted bi-lipid vesicles from human ESC-derived mesenchymal stem cells (hESC-MSCs) have been shown to reduce myocardial ischemia/reperfusion injury in animal models. However, as hESC-MSCs are not infinitely expansible, large scale production of these exosomes would require replenishment of hESC-MSC through derivation from hESCs and incur recurring costs for testing and validation of each new batch. Our aim was therefore to investigate if MYC immortalization of hESC-MSC would circumvent this constraint without compromising the production of therapeutically efficacious exosomes.