Asynchronous antigen expression in B lineage acute lymphoblastic leukemia

Cell surface phenotypes of 113 B lineage acute lymphocytic leukemia (ALL) cases, defined by the presence of HLA-DR and at least one B-cell- specific antigen (either CD19, CD20, or CD22), were compared with antigen-defined stages of normal B lymphocyte development. The cases were first evaluated for expression of HLA-DR, CD19, CD34, CD10, CD20, and CD22 by indirect one-color immunofluorescence. Pairwise comparisons of cell surface marker expression were performed for each leukemic sample: no correlations were observed for paired antigen expression on the leukemic samples using antigens expressed either early or late during normal B lymphoid development. Complete immunophenotypes of the cases were then compared with normal B-cell developmental stages. Sixteen different complete immunophenotypes were observed on the leukemias that were not found in normal marrow; at least 78% of the cases demonstrated such "asynchronous" combinations of B lymphoid- associated differentiation antigens. Several samples were subsequently studied by two-color immunofluorescence, and the presence of doubly labeled cells with "asynchronous" antigen combinations was confirmed. These results indicate that the majority of B lineage leukemias exhibit "developmental asynchrony," as compared with normal marrow B cells. The data further suggest that ALL cases do not accurately represent cells arrested at the stage where the leukemogenic event occurred. Rather, ALL appears to be a disease in which there may be maturation of leukemic blasts; but this maturation is "asynchronous" when compared with the normal developmental process.     

Successful allogeneic cryopreserved marrow transplantation

Cryopreservation has been used extensively in autologous marrow transplantation (BMT), but there has been limited use in allogeneic BMT. We describe here 6 cases of successful engraftment following allogeneic BMT with cryopreserved marrow. Patients suffered from Wiscott-Aldrich syndrome, osteopetrosis, aplastic anemia, and acute lymphocytic, acute non-lymphocytic, and chronic myelogenous leukemia, and ranged in age from 5 mos to 35 yrs. Marrow was collected using standard techniques. In one case T-cells were removed to prevent graft-vs-host disease. Marrow was frozen for a variety of reasons. Buffy coat cells were frozen at controlled rate in 10% DMSO, and stored in liquid nitrogen for 6 to 49 d. Engraftment (WBC greater than 1000/uL x 3 d) occurred from 13 to 37 d post BMT. In 4 of 4 cases in which data are available, donor origin of engraftment was documented, 1 with cytogenetics, 2 with red cell typing, and 4 with restriction fragment length polymorphisms. 3 patients are alive and well 21, 21, and 42 months post BMT. These results suggest frozen marrow can be successfully used for allogeneic BMT.     

A novel COL1A1 mutation in infantile cortical hyperostosis (Caffey disease) expands the spectrum of collagen-related disorders

Infantile cortical hyperostosis (Caffey disease) is characterized by spontaneous episodes of subperiosteal new bone formation along 1 or more bones commencing within the first 5 months of life. A genome-wide screen for genetic linkage in a large family with an autosomal dominant form of Caffey disease (ADC) revealed a locus on chromosome 17q21 (LOD score, 6.78). Affected individuals and obligate carriers were heterozygous for a missense mutation (3040Ctwo head right arrowT) in exon 41 of the gene encoding the alpha1(I) chain of type I collagen (COL1A1), altering residue 836 (R836C) in the triple-helical domain of this chain. The same mutation was identified in affected members of 2 unrelated, smaller families with ADC, but not in 2 prenatal cases and not in more than 300 chromosomes from healthy individuals. Fibroblast cultures from an affected individual produced abnormal disulfide-bonded dimeric alpha1(I) chains. Dermal collagen fibrils of the same individual were larger, more variable in shape and size, and less densely packed than those in control samples. Individuals bearing the mutation, whether they had experienced an episode of cortical hyperostosis or not, had joint hyperlaxity, hyperextensible skin, and inguinal hernias resembling symptoms of a mild form of Ehlers-Danlos syndrome type III. These findings extend the spectrum of COL1A1-related diseases to include a hyperostotic disorder.     

Direct demonstration of an HLA-DR allotypic determinant on the low molecular weight (beta) subunit using a mouse monoclonal antibody specific for DR3

A murine monoclonal antibody directed against a human B cell surface antigen with the characteristics of HLA-DR is described. The antigen detected is tightly linked to HLA and is correlated with the alloantigen HLA-Dw/DR3. Reactivity with a fraction of Dw/DRw6 cells is also observed. The determinant recognized by this antibody has been shown to be present on the smaller molecular weight β subunit of the HLA-DR antigen.     

A severe transfusion reaction associated with anti-EnaTS in a patient with an abnormal alpha-like red cell sialoglycoprotein

A 71-year-old woman (Ped) received 3 units of red cells (RBCs), compatible by the indirect antiglobulin test but strongly (4+) incompatible by direct agglutination at 37 degrees C. The next day, her plasma hemoglobin was 1252 mg percent and the direct antiglobulin test (DAT) was weakly positive (IgG and C3). Less than 5 percent of the transfused cells could be detected 48 hours posttransfusion. Her clinical condition deteriorated and renal failure developed. The patient died of pulmonary embolism. Her serum contained a strong (4+) IgM agglutinin and a weakly reactive (microscopically positive) IgG antibody, with anti-EnaTS specificity. EnaFS and EnaTS antigens were severely depressed or absent from the patient's RBCs; the ficin-resistant Ena antigen (EnaFR) appeared to be present. Pretransfusion RBC sialic acid level was 53 +/- 2 percent of normal. The patient's RBC membranes were shown to contain sialoglycoproteins beta and delta by sodium dodecyl sulphate polyacrylamide gel electrophoresis with periodic acid Schiff's base staining, with weak staining of components in the regions corresponding to alpha, alpha 2 and alpha delta. The nature of these components was not identified, but their presence suggested that the patient's RBCs expressed a previously undescribed sialoglycoprotein alpha variant.     

Untwist the twist: instant hemodynamic improvement in known HeartMate 3 complication

Journal of Artificial Organs - The HeartMate 3 [HM3 (Abbott, Abbott Park, Illinois)] is a left-ventricular assist device (LVAD) with excellent clinical results. Outflow graft occlusion as a...     

Left thoracotomy vs full sternotomy for centrifugal durable LVAD implantation: 1-year outcome comparison post-LVAD and post-heart transplantation

Journal of Artificial Organs - Left ventricular assist device (LVAD) implantations have traditionally been approached through a full median sternotomy (FS). Recently, a minimally invasive left...     

Human costs of aged care productivity: Innovation versus staffing and skills mix

ProblemThere is ongoing debate regarding the impact of, and relationship between, technological innovation and staffing levels and skills mix in aged care. Some commentators suggest that mandating minimum staffing levels and skills mix will undermine the sector’s ability to increase productivity via technological innovations.AimThis paper aims to stimulate scholarly debate regarding staffing levels, skills mix, and technological innovation in aged care.MethodsAs a discussion paper providing a scholarly and political critique of current policy issues affecting nurses and aged care, no reporting guideline has been followed.FindingsStaffing and skills mix in aged care has risen as a prominent, divisive issue. Some commentators suggest that productivity is hampered by mandating minimum staffing levels and skills mix by interfering with the uptake of innovation and technology. While technological innovation has led to many opportunities for better outcomes, we argue that without at least enough of the right kind of staff in aged care, technology and innovation alone cannot be relied upon to facilitate the dignified, person-centred care that older people deserve.DiscussionWe argue that staffing levels and skills mix need not be opposed to the implementation of innovations in aged care and that a focus on productivity and efficiency risks dehumanising the sector even further.ConclusionBy maximising labour potential in aged care, and enabling a sector that supports a suitably sized and skilled workforce to care for older people, we are supporting a workforce that is ready and able to leverage opportunities offered by innovations in ways that do not dehumanise our older people.