| 1. |
- Edebo, Anders, 1968, et al.
(författare)
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Circumferential and axial distribution of esophageal mucosal damage in reflux disease.
- 2007
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Ingår i: Diseases of the esophagus : official journal of the International Society for Diseases of the Esophagus / I.S.D.E. - : Oxford University Press (OUP). - 1120-8694. ; 20:3, s. 232-8
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to evaluate the axial and radial distribution of histological markers including hyperplasia of the basal cell layer, elongation of the papillae and dilatation of the intercellular spaces of the squamous epithelium in patients with nonerosive reflux disease compared to controls and to relate this to the macroscopic topography in erosive reflux disease. Two different study populations were included in this report. Endoscopic esophageal biopsies were taken from 21 healthy control subjects and 21 nonerosive reflux disease patients before and after 4 weeks of esomeprazole therapy. Endoscopic still images from 50 erosive reflux disease patients were reviewed for the radial orientation of LA grade A and/or B esophagitis (Los Angeles criteria for grading of reflux esophagitis). The 3 o'clock position of the squamocolumnar junction showed significantly thicker basal cell layer (P=0.011) and more intercellular space dilatation (P=0.01) in nonerosive reflux disease patients compared to the 9 o'clock position. Only a significant difference in dilatation of the intercellular spaces (P=0.018) between nonerosive reflux disease patients and controls were observed in the 3 o'clock region at the squamocolumnar junction, whereas 1-2 cm orally, all three histological criteria differed significantly (P
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| 2. |
- Budeus, B., et al.
(författare)
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Human cord blood b cells differ from the adult counterpart by conserved ig repertoires and accelerated response dynamics
- 2021
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Ingår i: Journal of Immunology. - : The American Association of Immunologists. - 0022-1767 .- 1550-6606. ; 206:12, s. 2839-2851
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Tidskriftsartikel (refereegranskat)abstract
- Neonatal and infant immune responses are characterized by a limited capability to generate protective Ab titers and memory B cells as seen in adults. Multiple studies support an immature or even impaired character of umbilical cord blood (UCB) B cells themselves. In this study, we provide a comprehensive molecular and functional comparison of B cell subsets from UCB and adult peripheral blood. Most UCB B cells have a mature, naive B cell phenotype as seen in adults. The UCB Ig repertoire is highly variable but interindividually conserved, as BCR clonotypes are frequently shared between neonates. Furthermore, UCB B cells show a distinct transcriptional program that confers accelerated responsiveness to stimulation and facilitated IgA class switching. Stimulation drives extensive differentiation into Ab-secreting cells, presumably limiting memory B cell formation. Humanized mice suggest that the distinctness of UCB versus adult B cells is already reflected by the developmental program of hematopoietic precursors, arguing for a layered B-1/B-2 lineage system as in mice, albeit our findings suggest only partial comparability to murine B-1 cells. Our study shows that UCB B cells are not immature or impaired but differ from their adult mature counterpart in a conserved BCR repertoire, efficient IgA class switching, and accelerated, likely transient response dynamics. © 2021 by TheAmericanAssociation of Immunologists, Inc.
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| 3. |
- Stockfelt, Marit, et al.
(författare)
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Plasma interferon-alpha is associated with double-positivity for autoantibodies but is not a predictor of remission in early rheumatoid arthritis-a spin-off study of the NORD-STAR randomized clinical trial
- 2021
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Ingår i: Arthritis Research & Therapy. - : Springer Science and Business Media LLC. - 1478-6354 .- 1478-6362. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- Background The type I interferon (IFN) gene signature is present in a subgroup of patients with early rheumatoid arthritis (RA). Protein levels of IFN alpha have not been measured in RA and it is unknown whether they associate with clinical characteristics or treatment effect. Methods Patients with early untreated RA (n = 347) were randomized to methotrexate combined with prednisone, certolizumab-pegol, abatacept, or tocilizumab. Plasma IFN alpha protein levels were determined by single molecular array (Simoa) before and 24 weeks after treatment initiation and were related to demographic and clinical factors including clinical disease activity index, disease activity score in 28 joints, swollen and tender joint counts, and patient global assessment. Results IFN alpha protein positivity was found in 26% of the patients, and of these, 92% were double-positive for rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA). IFN alpha protein levels were reduced 24 weeks after treatment initiation, and the absolute change was similar irrespective of treatment. IFN alpha protein positivity was associated neither with disease activity nor with achievement of CDAI remission 24 weeks after randomization. Conclusion IFN alpha protein positivity is present in a subgroup of patients with early RA and associates with double-positivity for autoantibodies but not with disease activity. Pre-treatment IFN alpha positivity did not predict remission in any of the treatment arms, suggesting that the IFN alpha system is distinct from the pathways of TNF, IL-6, and T-cell activation in early RA. A spin-off study of the NORD-STAR randomized clinical trial, NCT01491815 (ClinicalTrials), registered 12/08/2011, .
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| 4. |
- Baldaque-Silva, F., et al.
(författare)
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Impact of gastroesophageal reflux control through tailored proton pump inhibition therapy or fundoplication in patients with Barrett's esophagus
- 2017
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Ingår i: World Journal of Gastroenterology. - : Baishideng Publishing Group Inc.. - 1007-9327 .- 2219-2840. ; 23:17, s. 3174-3183
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Tidskriftsartikel (refereegranskat)abstract
- AIM To determine the impact of upwards titration of proton pump inhibition (PPI) on acid reflux, symptom scores and histology, compared to clinically successful fundoplication. Two cohorts of long-segment Barrett's esophagus (BE) patients were studied. In group 1 (n = 24), increasing doses of PPI were administered in 8-wk intervals until acid reflux normalization. At each assessment, ambulatory 24 h pH recording, endoscopy with biopsies and symptom scoring (by a gastroesophageal reflux disease health related quality of life questionnaire, GERD/HRLQ) were performed. Group 2 (n = 30) consisted of patients with a previous fundoplication. In group 1, acid reflux normalized in 23 of 24 patients, resulting in improved GERD/HRQL scores (P = 0.001), which were most pronounced after the starting dose of PPI (P < 0.001). PPI treatment reached the same level of GERD/HRQL scores as after a clinically successful fundoplication (P = 0.5). Normalization of acid reflux in both groups was associated with reduction in papillary length, basal cell layer thickness, intercellular space dilatation, and acute and chronic inflammation of squamous epithelium. This study shows that acid reflux and symptom scores co-vary throughout PPI increments in long-segment BE patients, especially after the first dose of PPI, reaching the same level as after a successful fundoplication. Minor changes were found among GERD markers at the morphological level.
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| 5. |
- Edebo, Anders, 1968, et al.
(författare)
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Magnification endoscopy for diagnosis of nonerosive reflux disease: a proposal of diagnostic criteria and critical analysis of observer variability.
- 2007
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Ingår i: Endoscopy. - : Georg Thieme Verlag KG. - 1438-8812 .- 0013-726X. ; 39:3, s. 195-201
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND STUDY AIMS: This study tested the diagnostic value of high-resolution endoscopy for the recognition of subtle diagnostic esophageal mucosal changes in nonerosive reflux disease. PATIENTS AND METHODS: Ten control subjects and eleven patients with nonerosive reflux disease confirmed by a validated questionnaire, standard endoscopy, and 24-hour pH-metry participated in the study. Still images were collected by high-resolution endoscopes from the distal esophagus in a standardized manner, incorporating iodine staining. Assessments were repeated in the patients with reflux disease after 4 weeks of esomeprazole therapy. Interobserver variability in the recognition of the proposed criteria was initially evaluated by 27 endoscopists using an Internet-based process. After optimisation of image quality the evaluation was repeated face-to-face with six expert endoscopists. RESULTS: No criterion was identified in either assessment that was sufficiently sensitive and specific to patients with reflux disease to be clinically useful. The kappa value, used to assess interobserver variation, was acceptably high only for invisibility of palisade vessels (0.59). Triangular indentations, apical mucosal breaks, and pinpoint blood vessels at the squamocolumnar junction were identified more frequently in the patients with reflux disease ( P < 0.05). These changes and the invisibility of the palisade vessels were significantly less prevalent in reflux patients after therapy ( P < 0.01). CONCLUSIONS: Though some distal esophageal mucosal appearances observed with the high-resolution endoscope appeared to be related to nonerosive esophageal mucosal injury, none of these changes proved to be sufficiently sensitive and specific to justify their use as a diagnostic criterion for nonerosive reflux disease.
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| 6. |
- Scarpellini, E., et al.
(författare)
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International consensus on the diagnosis and management of dumping syndrome
- 2020
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Ingår i: Nature Reviews Endocrinology. - : Springer Science and Business Media LLC. - 1759-5029 .- 1759-5037. ; 16:8, s. 448-466
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Tidskriftsartikel (refereegranskat)abstract
- Dumping syndrome is a common but underdiagnosed complication of gastric and oesophageal surgery. We initiated a Delphi consensus process with international multidisciplinary experts. We defined the scope, proposed statements and searched electronic databases to survey the literature. Eighteen experts participated in the literature summary and voting process evaluating 62 statements. We evaluated the quality of evidence using grading of recommendations assessment, development and evaluation (GRADE) criteria. Consensus (defined as >80% agreement) was reached for 33 of 62 statements, including the definition and symptom profile of dumping syndrome and its effect on quality of life. The panel agreed on the pathophysiological relevance of rapid passage of nutrients to the small bowel, on the role of decreased gastric volume capacity and release of glucagon-like peptide 1. Symptom recognition is crucial, and the modified oral glucose tolerance test, but not gastric emptying testing, is useful for diagnosis. An increase in haematocrit >3% or in pulse rate >10 bpm 30 min after the start of the glucose intake are diagnostic of early dumping syndrome, and a nadir hypoglycaemia level <50 mg/dl is diagnostic of late dumping syndrome. Dietary adjustment is the agreed first treatment step; acarbose is effective for late dumping syndrome symptoms and somatostatin analogues are preferred for patients who do not respond to diet adjustments and acarbose. Dumping syndrome is a frequent complication of oesophageal and gastric surgery, as well as bariatric surgery; however, guidance on how to manage patients with this condition is lacking. In this Evidence-based guideline, the authors use a Delphi consensus process to develop uniform guidance for the definition, diagnosis and management of dumping syndrome.
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| 7. |
- Aminoff, A, et al.
(författare)
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Allele-specific regulation of MTTP expression influences the risk of ischemic heart disease.
- 2010
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Ingår i: Journal of lipid research. - 0022-2275 .- 1539-7262. ; 51:1, s. 103-11
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Tidskriftsartikel (refereegranskat)abstract
- Promoter polymorphisms in microsomal triglyceride transfer protein (MTTP) have been associated with decreased plasma lipids but an increased risk for ischemic heart disease (IHD), indicating that MTTP influences the susceptibility for IHD independent of plasma lipids. The objective of this study was to characterize the functional promoter polymorphism in MTTP predisposing to IHD and its underlying mechanism. Use of pyrosequencing technology revealed that presence of the minor alleles of the promoter polymorphisms -493G>T and -164T>C result in lower transcription of MTTP in vivo in the heart, liver, and macrophages. In vitro experiments indicated that the minor -164C allele mediates the lower gene expression and that C/EBP binds to the polymorphic region in an allele-specific manner. Furthermore, homozygous carriers of the -164C were found to have increased risk for IHD as shown in a case-control study including a total of 544 IHD patients and 544 healthy control subjects. We concluded that carriers of the minor -164C allele have lower expression of MTTP in the heart, mediated at least partly by the transcription factor CCAAT/enhancer binding protein, and that reduced concentration of MTTP in the myocardium may contribute to IHD upon ischemic damage.
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| 8. |
- Cornell, David H., 1948, et al.
(författare)
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Zircon xenocrysts obscured the zircon date for the lower Koras Group, southern Africa
- 2023
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Ingår i: South African Journal of Geology. - 1012-0750. ; 126:2, s. 177-194
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Tidskriftsartikel (refereegranskat)abstract
- The Koras Group is a bimodal volcanosedimentary group located in post-tectonic grabens in a foreland thrust complex in the Kaaien Terrane of the Mesoproterozoic Namaqua-Natal Province of southern Africa. It contains two sequences of mafic and felsic volcanic rocks with an unconformity between them, only the lower sequence being slightly folded. The Koras Group was long regarded as having formed at the end of the 1 210 to 1 000 Ma Namaqua Orogeny, because it lacks the severe deformation and metamorphism of the underlying rocks, with igneous minerals preserved in many samples. Following years of unsuccessful attempts to precisely date the volcanic rocks, the first two ion probe U-Pb zircon studies both reported ages of-1 172 Ma for the Swartkopsleegte Formation felsic lava in the slightly folded lower sequence (based on relatively few dated zircons) and-1 100 Ma for the Leeuwdraai Formation rhyolite in the undeformed upper sequence. Thus a major 70 m.y. hiatus seemed apparent between the lower and upper sequences despite their similar geochemistry and rift-related setting. This gave rise to models which envisaged the Kaaien Terrane being unaffected by the syn-to late-tectonic deformation, migmatisation and granite intrusions, documented between 1 200 and 1 150 Ma in the adjoining Namaqua-Natal terranes to the west.A high-pressure (10 kbar) metamorphic event, recognised in the Kaaien Terrane basement just south of hardly deformed Koras Group exposures and dated at 1 150 Ma, is inconsistent with such models. A re-investigation and microbeam dating campaign on the Koras Group confirms the 1 101 & PLUSMN; 2 Ma (n = 6) age for felsic volcanic rocks of the upper sequence, but establishes a new reliable age of 1 114 & PLUSMN; 4 Ma for the lower one (n = 2). The 1 170 ages obtained in the earlier two studies were revisited and are now considered to reflect the age of zircon xenocrysts from the source rocks, which dominate the zircon population of some Swartkopsleegte Formation samples.Several criteria to distinguish autocrystic (magmatic) from antecrystic (age-overlappping xenocrystic) data points were investigated. One sample had high Th levels in only the younger zircons, but histograms of sufficiently precise 207Pb/206Pb ages provided the main criterion. Calculations of zircon crystallisation temperature intervals were not useful in predicting the abundance or proportions of magmatic and antecryst zircons. A multi-episode model of magmatic generation and crystallisation events is probably appropriate. In cases when felsic volcanic samples yield few zircons, care must be taken to avoid the problem exposed in this study.The Koras Group sediments have similar detrital zircon U/Pb age distributions to those of the Rehoboth Basement Inlier. This supports the concept that the Kaaien Terrane originated as the southern part of the Rehoboth Province.
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| 9. |
- Lund, M, et al.
(författare)
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Nitric oxide and endothelin-1 release after one-lung ventilation during thoracoabdominal esophagectomy.
- 2013
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Ingår i: Diseases of the esophagus. - : Oxford University Press (OUP). - 1120-8694. ; 26:8, s. 853-858
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Tidskriftsartikel (refereegranskat)abstract
- One-lung ventilation (OLV) is applied during esophagectomy to improve exposure during the thoracic part of the operation. Collapse of lung tissue, shunting of pulmonary blood flow, and changes in alveolar oxygenation during and after OLV may possibly induce an ischemia-reperfusion response in the lung, which may affect the pulmonary endothelium. Such a reaction might thereby contribute to the frequently occurring respiratory complications among these patients. In this small trial, 30 patients were randomized to either OLV (n= 16) or two-lung ventilation (TLV, n= 14) during esophagectomy. Central venous and arterial plasma samples were taken before and after OLV/TLV for analysis of nitrite and a metabolite of nitric oxide (NO), and also during the 1st, 2nd, 3rd, and 10th postoperative day for analysis of endothelin, another endothelium-derived vasoactive mediator. Lung biopsies were taken before and after OLV or TLV, and analyzed regarding immunofluorescence for isoform of NO synthase, a protein upregulated during inflammatory response and also vascular congestion. No changes in lung isoform of NO synthase immunofluorescence or vascular congestion were registered after neither OLV nor TLV. Plasma nitrite and endothelin levels were similar in the two study groups. We conclude that OLV does not seem to have any influence on key regulators of pulmonary vascular tone and inflammation, i.e. NO and endothelin. From this perspective, OLV seems to be a safe method, which defends its clinical position to facilitate surgical exposure during thoracoabdominal esophagectomy.
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| 10. |
- Vieth, M, et al.
(författare)
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Radial distribution of dilated intercellular spaces of the esophageal squamous epithelium in patients with reflux disease exhibiting discrete endoscopic lesions.
- 2004
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Ingår i: Digestive diseases (Basel, Switzerland). - : S. Karger AG. - 0257-2753 .- 1421-9875. ; 22:2, s. 208-12
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Dilatation of intercellular spaces of the esophageal squamous epithelium has been suggested as a marker of early acid reflux-induced damage. This change is a potentially useful addition to histomorphological changes that represent so called minimal endoscopic lesions. We have assessed dilatation of intercellular spaces with regard to: (1) interobserver variability, and (2) whether the incidence of this varies between 'red streaks' and the adjacent normal looking squamous epithelium. METHODS: Esophageal biopsies from 44 patients with chronic gastro-esophageal reflux (GERD) were evaluated. At endoscopy, these patients had one or more red streaks on the tops of the mucosal folds in the distal esophagus. Biopsies were taken from the red streaks and from the normal-appearing mucosa 1 cm lateral to the red streaks. Biopsies were assessed in a blinded fashion by two independent pathologists (MV & RF). Criteria for assessing intercellular space dilatation were evaluated and agreed on prior to the study. RESULTS: Good interobserver agreement was recorded (kappa = 0.82 at the streaks and 0.77 for the control tissues) for absence/presence of intercellular space dilatation. Red streak and control biopsies differed significantly (p = 0.0001), with respect to presence of dilated intercellular spaces, with 90.5 % of the former demonstrating this as present compared to 56.1% in the controls. CONCLUSION: This study supports the concept that esophageal mucosal minimal changes due to reflux is localised and that dilatation of intercellular spaces is an early sign of reflux-induced epithelial damage. The low interobserver variability in the assessment of intercellular space dilatation suggests that this may be a useful variable for assessment of early signs of acid-reflux induced damage to the squamous epithelium of the esophagus by use of light microscopy.
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