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  • 1.
    Ben-Yosef, Yaara
    et al.
    PixCell Med Technol Ltd, Yokneam Ilit, Israel.
    Marom, Barak
    PixCell Med Technol Ltd, Yokneam Ilit, Israel.
    Hirshberg, Galit
    PixCell Med Technol Ltd, Yokneam Ilit, Israel.
    D'Souza, Carol
    Univ Westminster, Fac Sci & Technol, Biomed Sci, London, England.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Bransky, Avishay
    PixCell Med Technol Ltd, Yokneam Ilit, Israel.
    The HemoScreen, a novel haematology analyser for the point of care2016In: Journal of Clinical Pathology, ISSN 0021-9746, E-ISSN 1472-4146, Vol. 69, no 8, p. 720-725Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND AIMS: A haematology analyser, based on a new technology, is presented herein. The analyser that provides a complete blood count (CBC) and five-part differential accepts disposable cartridges containing all required reagents, making it maintenance-free and ideal for point-of-care (POC) settings. The test reproducibility and imperviousness to analytical errors are attributed to the imaging-based analysis employed. Imaging enables cell-morphology-based differentiation, which is analogous to the gold standard microscopic analysis. This article presents the HemoScreen new technology and evaluates its performance through a small-scale study conducted in its designated clinical settings.

    METHODS: Thirty anticoagulated whole blood samples were analysed on the HemoScreen and Sysmex XE-2100. Linear regression was performed for the methods comparison. Two samples with 15 replicates were processed for imprecision. Ease of use of the device was also considered.

    RESULTS: The HemoScreen demonstrated acceptable imprecision and good agreement with the Sysmex XE-2100. The white blood cells (WBCs), red blood cells (RBCs), haemoglobin (HGB), haematocrit (HCT), platelets (PLT), neutrophils, lymphocytes and eosinophils have coefficients of correlation (r) >0.97. For mean cell volume (MCV), mean cell HGB (MCH) and RBC distribution width (RDW), r values ranged from 0.92 to 0.96. For mean cell HGB concentration (MCHC) and monocytes r=0.82 was demonstrated. User-friendliness and suitability of the device for operation in the designated POC settings was also confirmed.

    CONCLUSIONS: The HemoScreen employs innovative technologies of viscoelastic focusing and microfluidics within a disposable cartridge for an image-based blood cell analysis. By providing accurate and repeatable CBC and five-part differential results within minutes and maintaining the simplicity of operation, the HemoScreen could have far-reaching implications for use at POC. Further extended evaluation is in progress.

  • 2. Henriksson, A E
    et al.
    Vancea, E
    Pitkänen, P
    Wilander, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Pathology.
    Bergqvist, David
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Neuroendocrine tumour cells in the wall of a splenic artery aneurysm2007In: Journal of Clinical Pathology, ISSN 0021-9746, E-ISSN 1472-4146, Vol. 60, no 7, p. 837-838Article in journal (Refereed)
    Abstract [en]

    Neuroendocrine tumours are reported from the alimentary and respiratory tracts. A case of a 57-year-old man with an unsuspected histopathological finding of neuroendocrine tumour cells in the wall of a splenic artery aneurysm is reported.

    Visceral artery aneurysms are uncommon but clinically important owing to the risk of rupture and of intra-abdominal bleeding.1 There are several possible aetiologies, atherosclerosis being one, and often the cause is unknown or at least not stated.1 The case of a patient with two visceral artery aneurysms and unsuspected histopathological finding is reported.

  • 3. Jatta, K.
    et al.
    Eliason, G.
    Portela-Gomes, G. M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Grimelius, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Caro, O.
    Nilholm, L.
    Sirjsö, A.
    Piehl-Aulin, K.
    Abdel-Halim, S. M.
    Overexpression of von Hippel-Lindau protein in skeletal muscles of patients with chronic obstructive pulmonary disease2009In: Journal of Clinical Pathology, ISSN 0021-9746, E-ISSN 1472-4146, Vol. 62, no 1, p. 70-76Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: A significant number of patients with chronic obstructive pulmonary disease (COPD) exhibit skeletal muscle wasting and decreased capillary area formation, which correlate with increased mortality. AIM: To determine the molecular mechanisms mediating decreased capillary formation in COPD. METHODS: 24 patients with COPD and 12 matching controls were recruited. Patients with COPD were classified into mild, moderate and severe groups according to GOLD (global initiative for chronic obstructive lung disease) criteria. Biopsy specimens were obtained from the tibialis anterior muscle. Fibre typing and capillary formation, together with messenger RNA (mRNA) expression of hypoxia-inducible factors (HIF1alpha and HIF3alpha), vascular endothelial growth factors (VEGF-A, VEGF-B and VEGF-C isoforms) and von Hippel-Lindau (VHL) protein, were determined. VHL expression and localisation were further studied by immunohistochemistry. RESULTS: Skeletal muscle capillary formation decreased significantly with increasing disease severity. Compared with controls, a tendency to mRNA overexpression of HIF1alpha, HIF3alpha and VEGF isoforms was observed in mild and moderate COPD, which decreased at the severe stage. In contrast, skeletal muscle biopsy samples from patients with COPD exhibited significant overexpression of VHL at both the mRNA and protein level by immunohistochemistry. VHL protein was further determined to be localised to satellite cells. CONCLUSIONS: Overexpression of VHL was identified in the skeletal muscle of patients with COPD. Increased VHL activity may have a negative effect on transduction of the hypoxic signal and may contribute to decreased capillarisation in skeletal muscles of patients with COPD.

  • 4.
    Linder, Nina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH), International Child Health and Nutrition. Institute for Molecular Medicine Finland, HILIFE, University of Helsinki, Helsinki, Finland .
    Taylor, Jenny C
    Wellcome Trust Centre for Human Genetics, University of Oxford and Oxford NIHR Biomedical Research Centre, Oxford, UK .
    Colling, Richard
    Department of Cellular Pathology, Oxford University Hospitals NHS Foundation Trust, Oxford, UK .
    Pell, Robert
    Department of Cellular Pathology, Oxford University Hospitals NHS Foundation Trust, Oxford, UK .
    Alveyn, Edward
    University of Oxford, Medical School, Oxford, UK .
    Joseph, Johnson
    Department of Oncology, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
    Protheroe, Andrew
    Department of Oncology, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
    Lundin, Mikael
    Institute for Molecular Medicine Finland, HILIFE, University of Helsinki, Helsinki, Finland.
    Lundin, Johan
    Institute for Molecular Medicine Finland, HILIFE, University of Helsinki, Helsinki, Finland; Department of Public Health Sciences, Global Health/IHCAR, Karolinska Institutet, Stockholm, Sweden.
    Verrill, Clare
    Nuffield Department of Surgical Sciences and NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, UK .
    Deep learning for detecting tumour-infiltrating lymphocytes in testicular germ cell tumours2018In: Journal of Clinical Pathology, ISSN 0021-9746, E-ISSN 1472-4146, Vol. 72, no 2, p. 157-164Article in journal (Refereed)
    Abstract [en]

    AIMS: To evaluate if a deep learning algorithm can be trained to identify tumour-infiltrating lymphocytes (TILs) in tissue samples of testicular germ cell tumours and to assess whether the TIL counts correlate with relapse status of the patient.

    METHODS: TILs were manually annotated in 259 tumour regions from 28 whole-slide images (WSIs) of H&E-stained tissue samples. A deep learning algorithm was trained on half of the regions and tested on the other half. The algorithm was further applied to larger areas of tumour WSIs from 89 patients and correlated with clinicopathological data.

    RESULTS: A correlation coefficient of 0.89 was achieved when comparing the algorithm with the manual TIL count in the test set of images in which TILs were present (n=47). In the WSI regions from the 89 patient samples, the median TIL density was 1009/mm2. In seminomas, none of the relapsed patients belonged to the highest TIL density tertile (>2011/mm2). TIL quantifications performed visually by three pathologists on the same tumours were not significantly associated with outcome. The average interobserver agreement between the pathologists when assigning a patient into TIL tertiles was 0.32 (Kappa test) compared with 0.35 between the algorithm and the experts, respectively. A higher TIL density was associated with a lower clinical tumour stage, seminoma histology and lack of lymphovascular invasion.

    CONCLUSIONS: Deep learning-based image analysis can be used for detecting TILs in testicular germ cell cancer more objectively and it has potential for use as a prognostic marker for disease relapse.

  • 5. Madrigal, Irene
    et al.
    Isabel Alvarez-Mora, Maria
    Karlberg, Olof
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Rodriguez-Revenga, Laia
    Elurbe, Dei M.
    Rabionet, Raquel
    Mur, Antonio
    Pie, Juan
    Ballesta, Francisca
    Sauer, Sascha
    Syvänen, Ann-Christine
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine.
    Mila, Montserrat
    Efficient application of next-generation sequencing for the diagnosis of rare genetic syndromes2014In: Journal of Clinical Pathology, ISSN 0021-9746, E-ISSN 1472-4146, Vol. 67, no 12, p. 1099-1103Article in journal (Refereed)
    Abstract [en]

    Aims The causes of intellectual disability, which affects 1%-3% of the general population, are highly heterogeneous and the genetic defect remains unknown in around 40% of patients. The application of next-generation sequencing is changing the nature of biomedical diagnosis. This technology has quickly become the method of choice for searching for pathogenic mutations in rare uncharacterised genetic diseases. Methods Whole-exome sequencing was applied to a series of families affected with intellectual disability in order to identify variants underlying disease phenotypes. Results We present data of three families in which we identified the disease-causing mutations and which benefited from receiving a clinical diagnosis: Cornelia de Lange, Cohen syndrome and Dent-2 disease. The genetic heterogeneity and the variability in clinical presentation of these disorders could explain why these patients are difficult to diagnose. Conclusions The accessibility to next-generation sequencing allows clinicians to save much time and cost in identifying the aetiology of rare diseases. The presented cases are excellent examples that demonstrate the efficacy of next-generation sequencing in rare disease diagnosis.

  • 6.
    Sundbom, Marcus
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Elphick, D. A.
    Mahida, Y. R.
    Cunliffe, R. N.
    Midtvedt, T.
    Engstrand, L.
    Rubio, C.
    Axelsson, L. Göran
    Alteration in human defensin-5 expression following gastric bypass surgery2007In: Journal of Clinical Pathology, ISSN 0021-9746, E-ISSN 1472-4146, Vol. 60, no 9, p. 1029-1034Article in journal (Refereed)
    Abstract [en]

    Background: Roux-en-Y gastric bypass surgery provides a novel human model to investigate small bowel mucosal innate immunity, in which there is loss of gastric acid-mediated protection against orally-acquired microorganisms. Aim: To study changes in jejunal mucosal immunoreactivity of human defensin (HD)-5,an antimicrobial peptide normally produced by Paneth cells. Methods: Mucosal samples were obtained from 18 female patients ( 24 - 54 years), from the same segment of jejunum during and after gastric bypass surgery. Samples were used for bacterial culture and immunohistochemistry using anti-HD-5 antibody. The number of immunoreactive cells per crypt and villus were determined and expressed as mean (SD). Results: No bacteria were cultured from any of the perioperative jejunal samples but colonies of bacteria normally present in the pharynx were identified during culture of all postoperative jejunal biopsy specimens (1-> 100 colonies). Paneth cell numbers per crypt were unchanged after gastric bypass ( 4.16 (0.71) vs 4.24 (0.78)). However, following surgery, there was an increase in HD-5-positive intermediate cells per crypt (0.25 (0.41) vs 1.12 (0.66), p < 0.01), HD-5 staining enterocytes per crypt ( 0.03 ( 0.09) vs 1.38 ( 1.10), p < 0.01), HD-5 staining material in the crypt lumen (crypt lumens: 5.0% ( 10.9%) vs 68.1% ( 27.9%), p < 0.01) and HD-5 immunoreactivity coating the luminal surface of villus enterocytes ( villi sampled: 15.0% ( 31.0%) vs 67.5% ( 42.0%), p < 0.01). Conclusions: Bacteria normally resident in the pharynx were present in the proximal jejunal mucosa following Roux-en-Y gastric bypass surgery. After gastric bypass, there was increased secretion of HD-5 and an increase in HD-5 expressing intermediate cells and enterocytes in the crypt. The increase in HD-5 expression in the jejunal mucosa following gastric bypass surgery is likely to be secondary to exposure to orally-acquired microorganisms.

1 - 6 of 6
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