The assessment of pain: an audit of physiotherapy practice

This study concerned the adoption of scientific method by the physiotherapy profession, with pain measurement as the research focus. It involved an audit of 1010 patient records from four hospital physiotherapy departments in England, to determine how pain was assessed and recorded. The results show that while pain assessment was recorded in most of the cases audited, there was no record of reassessment in 29 per cent of cases. In the initial assessment, only 21 per cent of cases involved quantified methods, reducing to less than 2 per cent during reassessment. These results indicate that the use of recognised quantified methods for pain assessment was not standard practice amongst the physiotherapists audited. Implications for the adoption of scientific method are discussed

Human embryonic stem cells hemangioblast express HLA-antigens

Abstract Background It has been suggested that the initial differentiation of endothelial and hematopoietic cells during embryogenesis occurs from a common progenitor, called hemangioblast (hB). We hypothesized that these cells with dual hematopoietic/endothelial potential could be used in future regenerative medicine. Methods We used the two-step differentiation technology to generate bipotential blast cells from human embryonic stem cells (hES). This involved short differentiation in our in vitro EB system followed by differentiation in semisolid culture medium supplemented with mixture of cytokines. Results The occurrence of blast-colony-forming cells (BL-CFC) during EB differentiation (day 0–6) was transient and peaked on day 3. The emergence of this event was associated with expression of mesoderm gene T, and inversely correlated with expression of endoderm gene FoxA2. Similarly, the highest BL-CFC number was associated with increase in expression of early hematopoietic/endothelial genes: CD34, CD31 and KDR. The derived colonies were composed of 30–50 blast cells on day 6 in culture. These cells had homogenous appearance in Wright-Giemsa stain, but to a different extent expressed markers of immature hematopoietic and endothelial cells (CD31, CD34, VE-cadherin, Flt-1) and mature differentiated cells (CD45, CD33, CD146). We found that some of them expressed fetal and embryonic globin genes. Interestingly, these cells expressed also HLA class I molecules, however at very low levels compared to endothelial and hematopoietic cells. The blast cells could be successfully differentiated to hematopoietic cells in a CFU assay. In these conditions, blast cells formed CFU-M colonies (63.4 ± 0.8%) containing macrophages, BFU-E colonies (19.5 ± 3.5%) containing nucleated red blood cells, and CFU-EM colonies (17.1 ± 2.7%) composed of macrophages and nucleated erythrocytes. Cells of CFU-EM and BFU-E colonies expressed both ε – and γ- globin genes, but not adult-type γ-globin. When in endothelial cell culture conditions, blast cells differentiated to endothelial cells which had the ability to take up Dil-Ac-LDL and to form complex vascular networks in Matrigel. Conclusion 1) Hematoendothelial precursors exist transiently in early embryonic development and form single cell-derived colonies; 2) their differentiation can be tracked by the use of chosen molecular markers; 3) blast colonies consist of cells having properties of endothelial and hematopoietic precursors, however the issue of their ability to maintain dual properties over time needs to be further explored; 4) blast cells can potentially be used in regenerative medicine due to their low expression of HLA molecules.</p

Human Embryonic Stem Cells Hemangioblast Express HLA-antigens

Background: It has been suggested that the initial differentiation of endothelial and hematopoietic cells during embryogenesis occurs from a common progenitor, called hemangioblast (hB). We hypothesized that these cells with dual hematopoietic/endothelial potential could be used in future regenerative medicine. Methods: We used the two-step differentiation technology to generate bipotential blast cells from human embryonic stem cells (hES). This involved short differentiation in our in vitro EB system followed by differentiation in semisolid culture medium supplemented with mixture of cytokines. Results: The occurrence of blast-colony-forming cells (BL-CFC) during EB differentiation (day 0-6) was transient and peaked on day 3. The emergence of this event was associated with expression of mesoderm gene T, and inversely correlated with expression of endoderm gene FoxA2. Similarly, the highest BL-CFC number was associated with increase in expression of early hematopoietic/endothelial genes: CD34, CD31 and KDR. The derived colonies were composed of 30-50 blast cells on day 6 in culture. These cells had homogenous appearance in Wright-Giemsa stain, but to a different extent expressed markers of immature hematopoietic and endothelial cells (CD31, CD34, VE-cadherin, Flt-1) and mature differentiated cells (CD45, CD33, CD146). We found that some of them expressed fetal and embryonic globin genes. Interestingly, these cells expressed also HLA class I molecules, however at very low levels compared to endothelial and hematopoietic cells. The blast cells could be successfully differentiated to hematopoietic cells in a CFU assay. In these conditions, blast cells formed CFU-M colonies (63.4 +/- 0.8%) containing macrophages, BFU-E colonies (19.5 +/- 3.5%) containing nucleated red blood cells, and CFU-EM colonies (17.1 +/- 2.7%) composed of macrophages and nucleated erythrocytes. Cells of CFU-EM and BFU-E colonies expressed both epsilon - and gamma- globin genes, but not adult-type gamma-globin. When in endothelial cell culture conditions, blast cells differentiated to endothelial cells which had the ability to take up Dil-Ac-LDL and to form complex vascular networks in Matrigel. Conclusion: 1) Hematoendothelial precursors exist transiently in early embryonic development and form single cell-derived colonies; 2) their differentiation can be tracked by the use of chosen molecular markers; 3) blast colonies consist of cells having properties of endothelial and hematopoietic precursors, however the issue of their ability to maintain dual properties over time needs to be further explored; 4) blast cells can potentially be used in regenerative medicine due to their low expression of HLA molecules

Efficacy and safety of empagliflozin in glycogen storage disease type Ib: Data from an international questionnaire

PURPOSE: This paper aims to report collective information on safety and efficacy of empagliflozin drug repurposing in individuals with glycogen storage disease type Ib (GSD Ib). METHODS: This is an international retrospective questionnaire study on the safety and efficacy of empagliflozin use for management of neutropenia/neutrophil dysfunction in patients with GSD Ib, conducted among the respective health care providers from 24 countries across the globe. RESULTS: Clinical data from 112 individuals with GSD Ib were evaluated, representing a total of 94 treatment years. The median age at start of empagliflozin treatment was 10.5 years (range = 0-38 years). Empagliflozin showed positive effects on all neutrophil dysfunction-related symptoms, including oral and urogenital mucosal lesions, recurrent infections, skin abscesses, inflammatory bowel disease, and anemia. Before initiating empagliflozin, most patients with GSD Ib were on G-CSF (94/112; 84%). At the time of the survey, 49 of 89 (55%) patients previously treated with G-CSF had completely stopped G-CSF, and another 15 (17%) were able to reduce the dose. The most common adverse event during empagliflozin treatment was hypoglycemia, occurring in 18% of individuals. CONCLUSION: Empagliflozin has a favorable effect on neutropenia/neutrophil dysfunction-related symptoms and safety profile in individuals with GSD Ib

Efficacy and safety of empagliflozin in glycogen storage disease type Ib: Data from an international questionnaire.

PURPOSE This paper aims to report collective information on safety and efficacy of empagliflozin drug repurposing in individuals with glycogen storage disease type Ib (GSD Ib). METHODS This is an international retrospective questionnaire study on the safety and efficacy of empagliflozin use for management of neutropenia/neutrophil dysfunction in patients with GSD Ib, conducted among the respective health care providers from 24 countries across the globe. RESULTS Clinical data from 112 individuals with GSD Ib were evaluated, representing a total of 94 treatment years. The median age at start of empagliflozin treatment was 10.5 years (range = 0-38 years). Empagliflozin showed positive effects on all neutrophil dysfunction-related symptoms, including oral and urogenital mucosal lesions, recurrent infections, skin abscesses, inflammatory bowel disease, and anemia. Before initiating empagliflozin, most patients with GSD Ib were on G-CSF (94/112; 84%). At the time of the survey, 49 of 89 (55%) patients previously treated with G-CSF had completely stopped G-CSF, and another 15 (17%) were able to reduce the dose. The most common adverse event during empagliflozin treatment was hypoglycemia, occurring in 18% of individuals. CONCLUSION Empagliflozin has a favorable effect on neutropenia/neutrophil dysfunction-related symptoms and safety profile in individuals with GSD Ib