A preliminary study on electromyographic analysis of the paraspinal musculature in idiopathic scoliosis

The paraspinal muscles have been implicated as a major causative factor in the progression of idiopathic scoliosis. Therefore, the objectives of this preliminary study were to measure the electromyographic activity (EMG) of the paraspinal muscles to determine its relationship to progression of the scoliotic curve. Idiopathic scoliotic patients were selected and identified afterwards on curve progression. The EMG activity on both sides of the spine was measured in a set of standardized postures using bipolar surface electrodes at the apex and two end vertebrae of the scoliotic curve. An EMG ratio involving measurements of the EMG activity on the convex and concave sides of the scoliotic curve was used to evaluate the paraspinal muscles. Enhanced EMG ratios at the apex of the scoliotic curve were found in both groups during sitting and standing. The most interesting finding was that children with progression of the curve also showed enhanced EMG ratios at the lower end vertebra of the curve. The EMG ratios between the groups were significantly different from each other at the apex and end vertebrae for several test conditions. Overlap in the EMG-ratio ranges made differentiation difficult for prediction of the progression of the individual scoliosis patient. However, the EMG ratio at the lower end vertebra of the scoliotic curve is significantly higher than 1 in all test conditions in the group of children with subsequent progression of the curve, whereas it is always normal in the non-progressive group. Therefore, EMG of the paraspinal muscles might be of value for prediction of progression in idiopathic scoliosis.     

Heparan sulfate control of proliferation and differentiation in the stem cell niche

Tissue-specific stem cell populations are established in "niches," anatomic locations with precise biochemical and cellular configurations that regulate their release and participation in tissue generation, maintenance, and repair. Niches have evolved to protect and perpetuate the self-renewing, undifferentiated state of the cells within and to regulate the rate of production of committed, tissue-specific progenitors. A niche thus integrates the cell growth, cell adhesion, and cell-cell signals that mediate the balanced response of stem cells to the needs of the organism. One constituent of every niche with the capacity to mediate almost all of the required functions is the glycosaminoglycan sugar heparan sulfate. This sugar is a master regulator of mitogenic and adhesive molecule behavior with the ability to rapidly change its binding affinities on the cell surface. Its properties may be the key to understanding the interplay between stem cells and their niche that creates the dynamic system necessary for sustaining tissues. As such, it has great promise for the design of tissue-specific stem cell therapeutics.     

Hospital Inpatient Admissions With Dehydration and/or Malnutrition in Medicare Beneficiaries Receiving Enteral Nutrition: A Cohort Study

Background: Enteral nutrition (EN) supports many older and disabled Americans. This study describes the frequency and cost of acute care hospitalization with dehydration and/or malnutrition of Medicare beneficiaries receiving EN, focusing on those receiving home EN. Methods: Medicare 5% Standard Analytic Files were used to determine Medicare spending for EN supplies and the proportion and cost of beneficiaries receiving EN, specifically home EN, admitted to the hospital with dehydration and/or malnutrition. Results: In 2013, Medicare paid $370,549,760 to provide EN supplies for 125,440 beneficiaries, 55% of whom were also eligible for Medicaid. Acute care hospitalization with dehydration and/or malnutrition occurred in 43,180 beneficiaries receiving EN. The most common principal diagnoses were septicemia (21%), aspiration pneumonitis (9%), and pneumonia (5%). In beneficiaries receiving EN at home, >one‐third (37%) were admitted with dehydration and/or malnutrition during a mean observation interval of 231 ± 187 days. Admitted patients were usually hospitalized more than once with dehydration and/or malnutrition (1.73 ± 1.30 admissions) costing $23,579 ± 24,966 per admitted patient, totaling >$129,685,622 during a mean observation interval of 276 ± 187 days. Mortality in the year following enterostomy tube placement was significantly higher for admitted compared with nonadmitted patients (40% vs 33%; P = .05). Conclusion: Acute care hospitalizations with dehydration and/or malnutrition in Medicare beneficiaries receiving EN were common and expensive. Additional strategies to reduce these, with particular focus on vulnerable populations such as Medicaid‐eligible patients, are needed.     

Function of wild-type or mutant Rac2 and Rap1a GTPases in differentiated HL60 cell NADPH oxidase activation

Studies of neutrophil nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation in a cell-free system showed that the low molecular-weight guanosine triphosphatase (GTPase) Rac was required, and that Rap1a may participate in activation of the catalytic complex. Full-length posttranslationally modified Rac2 was active, whereas only the 1-166 truncated form of Rap1a was functional in the cell-free system, and thus, clarification of the function of Rap1a and Rac2 in intact human phagocytes is needed to provide further insight into their roles as signal transducers from plasma membrane receptors. In the present studies, oligonucleotide-directed mutagenesis was used to introduce a series of mutations into human rap1a or rac2 in the mammalian expression vector pSR alpha neo. HL60 cells transfected with wild-type or mutated rac2 or rap1a cDNA constructs and control HL60 cells transfected with the pSR alpha neo vector containing no inserted cDNA were selected in G418-containing media, then subclones were isolated. Compared with the parent HL60 cells, each of the stable transfected cell lines differentiated similarly into neutrophil-like cells and expressed comparable levels of NADPH oxidase components p47- phox, p67-phox and gp91-phox. The differentiated vector control cell line produced O2. in response to receptor stimulation at rates that were not significantly different from parent HL60 cells. O2-. production by differentiated cell lines expressing mutated N17 Rap1a or N17 Rac2 dominant-negative proteins was inhibited, whereas O2-. production by the subline overexpressing wild-type Rap1a was increased by fourfold. O2-. production by the differentiated cell line expressing GTPase-defective V12 Rap1a was also significantly inhibited, a finding that is consistent with a requirement for cycling between guanosine diphosphate- and GTP-bound forms of Rap1a for continuous NADPH oxidase activation in intact neutrophils. A model is proposed in which Rac2 mediates assembly of the p47 and p67 oxidase components on the cytosolic face of the plasma membrane via cytoskeletal reorganization, whereas Rap1a functions downstream as the final activation switch involving direct physical interaction with the transmembrane flavocytochrome component of the NADPH oxidase.     

Unrelated donor marrow transplantation in children

Eighty-eight children 0.5 to 17 years of age (median, 9 years of age) received an unrelated donor marrow transplant for treatment of chronic myeloid leukemia (CML; n = 16), acute lymphoblastic leukemia (ALL) in first or second remission (n = 15) or more advanced stage (n = 28), acute myeloid leukemia (AML; n = 13), or other hematologic diseases (n = 16) between June 1985 and April 1993. All patients were conditioned with cyclophosphamide and total body irradiation and received a combination of methotrexate and cyclosporine as graft-versus-host disease (GVHD) prophylaxis. Fourty-six patients received transplants from HLA-identical donors and 42 patients received transplants from donors who were minor-mismatched at one HLA-A or B or D/DRB1 locus. The Kaplan-Meier estimates of disease-free survival and relapse were 75% and 0% for patients with CML, 47% and 20% for ALL in first or second remission, 10% and 60% for ALL in relapse or third remission, 46% and 46% for AML in first remission (n = 1) or more advanced disease (n = 12), and 29% and 69% for other diseases. HLA disparity was not significantly associated with lower disease-free survival, but the results suggest more relapses in HLA-matched recipients and there was significantly more transplant-related mortality in mismatched recipients (51% v 24%, P = .04). Most deaths were due to infections associated with acuteor chronic GVHD and occurred within the first 2 years after transplantation. Granulocyte engraftment occurred in all evaluable patients. Sixty-three percent of HLA-matched and 57% of HLA- mismatched recipients were discharged home disease-free at a median of 98 and 103 days, respectively, after transplantation (P = not significant [NS]). The incidence of grades II-IV acute GVHD was 83% in HLA-matched and 98% in HLA-mismatched recipients (P = .009). The incidence of chronic GVHD was 60% in HLA-matched and 69% in HLA- mismatched recipients (P = NS). One or multiple late adverse events such as cataracts, osteonecrosis of the hip or knee, restrictive or obstructive pulmonary disease, and hypothyroidism have occurred in 11 of 33 (33%) surviving patients. Immunosuppression was discontinued in 58% of surviving patients, including all 12 patients surviving more than 3.2 years, all of whom have a Lansky or Karnofsky score of 100%.(ABSTRACT TRUNCATED AT 400 WORDS)     

Studies on levamisole--induced agranulocytosis

Widespread clinical trials of leavo-tetramisole (levamisole) as an immunopotentiating agent in rheumatoid arthritis, metastatic carcinoma, and immunodeficiency states have been complicated by agranulocytosis (AGC) in 2.5%-13% of patients. Other than a relationship with prolonged high dosage, very little is known regarding the pathogenesis of levamisole-induced AGC. Whereas leukoagglutination was negative, fluorochromatic microgranulocytotoxicity (GCY) tests were positive with serum from 10 of 10 acutely neutropenic patients. The antibody was IgM, reacted with 100% of unrelated granulocytes, but not with T or B lymphocytes. Some sera also reacted with monocytes and the myeloid cell line, K-562. Tests for antigen-antibody complexes or cold autoantibodies were negative. Although clinical evidence strongly suggests a haptene (drug) mechanism, in vitro mixing experiments were also negative. An alternative choice parallels the model of aldomet- induced Coombs'-positive hemolytic anemia. Finally, GCY first became positive 2-3 mo prior to the onset of AGC on two patients, suggesting the possibility of identifying those at risk well before the onset of neutropenia.