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Sökning: WFRF:(Wanders Alkwin)

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  • Föregående 12[3]45Nästa
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  • Liu, Bojing, et al. (författare)
  • Vagotomy and subsequent risk of inflammatory bowel disease : a nationwide register-based matched cohort study
  • 2020
  • Ingår i: Alimentary Pharmacology and Therapeutics. - John Wiley & Sons. - 0269-2813 .- 1365-2036. ; 51:11, s. 1022-1030
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The vagus nerve provides essential parasympathetic innervation to the gastrointestinal system and is known to have anti‐inflammatory properties.Aims: To explore the relationship between vagotomy and the risk of inflammatory bowel disease (IBD) and its major categories: Crohn's disease (CD) and ulcerative colitis (UC).Methods: A matched cohort comprising 15 637 patients undergoing vagotomy was identified through the Swedish Patient Register from 1964 to 2010. Each vagotomised patient was matched for birth year and gender with 40 nonvagotomised individuals on the date of vagotomy. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for IBD using flexible parametric models adjusted for matching variables, year of vagotomy, birth country, chronic obstructive pulmonary disease and comorbidity index.Results: We observed 119 (0.8%) patients with vagotomy developed IBD compared to 3377 (0.5%) IBD cases in nonvagotomised individuals. The crude incidence of IBD (per 1000 person‐years) was 0.38 for vagotomised patients and 0.25 for nonvagotomised individuals. We observed a time‐dependent elevated risk of IBD associated with vagotomy, for instance, the HR (95% CI) was 1.80 (1.40‐2.31) at year 5 and 1.49 (1.14‐1.96) at year 10 post‐vagotomy. The association appeared to be stronger for truncal than selective vagotomy and limited to CD (HR was 3.63 [1.94‐6.80] for truncal and 2.06 [1.49‐2.84] for selective vagotomy) but not UC (1.36 [0.71‐2.62] for truncal and 1.25 [0.95‐1.63] for selective vagotomy).Conclusions: We found a positive association between vagotomy and later IBD, particularly for CD. The finding indirectly underlines the beneficial role of the vagal tone in IBD.
  • Malmström, Per-Uno, et al. (författare)
  • AdCD40L Immunogene Therapy for Bladder Carcinoma : The First Phase I/IIa Trial
  • 2010
  • Ingår i: Clinical Cancer Research. - 1078-0432 .- 1557-3265. ; 16:12, s. 3279-3287
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE: Immunotherapy with bacillus Calmette-Guérin (BCG) instillation is recommended for high-risk non-muscle invasive bladder cancer. BCG is not effective in advanced tumors, and better alternatives are warranted. Immunostimulating gene therapy with adenoviral vectors expressing CD40L (AdCD40L) has shown efficacy in tumor models. CD40L stimulates systemic immunity and may be effective in local and invasive human disease. EXPERIMENTAL DESIGN: Patients with invasive bladder cancer scheduled for cystectomy or patients with Ta tumors were enrolled in a Phase I/IIa trial. Patients were treated with three cycles of intra-bladder Clorpactin WCS-90 prewash followed by AdCD40L instillation one week apart. Safety, gene transfer, immune effects and anti-tumor responses were monitored. RESULTS: All eight recruited patients were treated as scheduled, and therapy was well tolerated. The main adverse effect was transient local pain during prewash. Postoperatively, urinary tract infections and one case of late septicemia with elevated potassium were reported. No adverse events were ascribed to vector therapy. Gene transfer was detected in biopsies and bladders were heavily infiltrated with T-cells. The effector marker IFNg increased in biopsies while levels of circulating T regulatory cells were reduced. Histological evaluation indicated that AdCD40L therapy reduced the load of malignant cells. CONCLUSION: To our knowledge, this is the first report on immunogene therapy in bladder cancer and the first utilizing AdCD40L in vivo. Local AdCD40L gene therapy was safe, boosted immune activation and should be further evaluated as single or adjuvant therapy for urothelial malignancies.
  • Markasz, Laszlo, et al. (författare)
  • Diminished DEFA6 Expression in Paneth Cells Is Associated with Necrotizing Enterocolitis
  • 2018
  • Ingår i: Gastroenterology Research and Practice. - Hindawi Publishing Corporation. - 1687-6121 .- 1687-630X.
  • Tidskriftsartikel (refereegranskat)abstract
    • Background. Necrotizing enterocolitis (NEC) is the most common gastrointestinal disorder in premature infants with a high morbidity and mortality. Paneth cell dysfunction has been suggested to be involved in the pathogenesis of NEC. Defensin alpha-6 (DEFA6) is a specific marker for Paneth cells acting as part of the innate immunity in the human intestines. The aim of this study was to investigate the expression of DEFA6 in infants with NEC. Materials and Methods. Infants who underwent bowel resection for NEC at level III NICU in Sweden between August 2004 and September 2013 were eligible for the study. Macroscopically vital tissues were selected for histopathological evaluation. All infants in the control group underwent laparotomy and had ileostomy due to dysmotility, and samples were taken from the site of the stoma. DEFA6 expression was studied by immunohistochemistry. Digital image analysis was used for an objective and precise description of the samples. Results. A total of 12 infants were included in the study, eight with NEC and four controls. The tissue samples were taken from the colon (n = 1), jejunum (n = 1), and ileum (n = 10). Both the NEC and control groups consisted of extremely premature and term infants (control group: 25-40 gestational weeks, NEC group: 23-39 gestational weeks). The postnatal age at the time of surgery varied in both groups (control group: 4-47 days, NEC group: 4-50 days). DEFA6 expression in the NEC group was significantly lower than that in the control group and did not correlate with gestational age. Conclusion. The diminished DEFA6 expression in Paneth cells associated with NEC in this study supports the hypothesis that alpha-defensins are involved in the pathophysiology of NEC. Future studies are needed to elucidate the role of alpha-defensins in NEC aiming at finding preventive and therapeutic strategies against NEC.
  • Marthinsen, Lars, et al. (författare)
  • Kolonspiroketos - behandlingsbart och värt att uppmärksamma : Erfarenheter från pediatrisk praktik
  • 2006
  • Ingår i: Läkartidningen. - 0023-7205 .- 1652-7518. ; 103:46, s. 3600-3602
  • Forskningsöversikt (övrigt vetenskapligt)abstract
    • This article is written to raise awareness among clinicians and pathologists regarding the existence of colonic spirochetosis. Whether this is of clinical significance is still a matter of debate. We report a series of sixteen randomly selected patients, all of paediatric age; eight of them have been reported in a previous publication (10). In one patient, spirochetes were found both in the colon and in the liver. The colon organisms were Brachyspira aalborgi, documented by antigen test; however, due to lack of material, the spirochetes in the liver could not be typed. As 10 of 13 patients recovered or improved after antibiotic treatment with clarythromycin or metronidazole, our conclusion is that Brachyspira may be pathogenic. We suggest that when a rectosigmoidoscopy/colonoscopy is performed, colonic spirochetosis should be considered, especially in the differential diagnosis to microscopic colitis.
  • Nordling, Sofia, et al. (författare)
  • Enhanced protection of the renal vascular endothelium improves early outcome in kidney transplantation Preclinical investigations in pig and mouse
  • 2018
  • Ingår i: Scientific Reports. - Nature Publishing Group. - 2045-2322 .- 2045-2322. ; 8
  • Tidskriftsartikel (refereegranskat)abstract
    • Ischemia reperfusion injury is one of the major complications responsible for delayed graft function in kidney transplantation. Applications to reduce reperfusion injury are essential due to the widespread use of kidneys from deceased organ donors where the risk for delayed graft function is especially prominent. We have recently shown that coating of inflamed or damaged endothelial cells with a unique heparin conjugate reduces thrombosis and leukocyte recruitment. In this study we evaluated the binding capacity of the heparin conjugate to cultured human endothelial cells, to kidneys from brain-dead porcine donors, and to murine kidneys during static cold storage. The heparin conjugate was able to stably bind cultured endothelial cells with high avidity, and to the renal vasculature of explanted kidneys from pigs and mice. Treatment of murine kidneys prior to transplantation reduced platelet deposition and leukocyte infiltration 24 hours post-transplantation, and significantly improved graft function. The present study thus shows the benefits of enhanced protection of the renal vasculature during cold storage, whereby increasing the antithrombotic and anti-adhesive properties of the vascular endothelium yields improved renal function early after transplantation.
  • Nyström, Niklas, et al. (författare)
  • Human enterovirus species B in ileocecal Crohn's disease
  • 2013
  • Ingår i: Clinical and Translational Gastroenterology. - 2155-384X .- 2155-384X. ; 4
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES:Advanced ileocecal Crohn's disease (ICD) is characterized by strictures, inflammation in the enteric nervous system (myenteric plexitis), and a high frequency of NOD2 mutations. Recent findings implicate a role of NOD2 and another CD susceptibility gene, ATG16L1, in the host response against single-stranded RNA (ssRNA) viruses. However, the role of viruses in CD is unknown. We hypothesized that human enterovirus species B (HEV-B), which are ssRNA viruses with dual tropism both for the intestinal epithelium and the nervous system, could play a role in ICD.METHODS:We used immunohistochemistry and in situ hybridization to study the general presence of HEV-B and the presence of the two HEV-B subspecies, Coxsackie B virus (CBV) and Echovirus, in ileocecal resections from 9 children with advanced, stricturing ICD and 6 patients with volvulus, and in intestinal biopsies from 15 CD patients at the time of diagnosis.RESULTS:All patients with ICD had disease-associated polymorphisms in NOD2 or ATG16L1. Positive staining for HEV-B was detected both in the mucosa and in myenteric nerve ganglia in all ICD patients, but in none of the volvulus patients. Expression of the cellular receptor for CBV, CAR, was detected in nerve cell ganglia.CONCLUSIONS:The common presence of HEV-B in the mucosa and enteric nervous system of ICD patients in this small cohort is a novel finding that warrants further investigation to analyze whether HEV-B has a role in disease onset or progress. The presence of CAR in myenteric nerve cell ganglia provides a possible route of entry for CBV into the enteric nervous system.
  • Ramachandran, Mohanraj, 1988-, et al. (författare)
  • An infection-enhanced oncolytic adenovirus secreting H. pylori neutrophil-activating protein with therapeutic effects on neuroendocrine tumors
  • 2013
  • Ingår i: Molecular Therapy. - 1525-0016 .- 1525-0024. ; 21:11, s. 2008-2018
  • Tidskriftsartikel (refereegranskat)abstract
    • Helicobacter pylori Neutrophil Activating Protein (HP-NAP) is a major virulence factor involved in H. pylori infection. HP-NAP can mediate anti-tumor effects by recruiting neutrophils and inducing Th1-type differentiation in the tumor microenvironment. It therefore holds strong potential as a therapeutic gene. Here, we armed a replication-selective, infection-enhanced adenovirus with secretory HP-NAP, Ad5PTDf35-[Δ24-sNAP], and evaluated its therapeutic efficacy against neuroendocrine tumors. We observed that it could specifically infect and eradicate a wide range of tumor cells lines from different origin in vitro. Insertion of secretory HP-NAP did not affect the stability or replicative capacity of the virus and infected tumor cells could efficiently secrete HP-NAP. Intratumoral administration of the virus in nude mice xenografted with neuroendocrine tumors improved median survival. Evidence of biological HP-NAP activity was observed 24 hours after treatment with neutrophil infiltration in tumors and an increase of proinflammatory cytokines such as TNF-α and MIP2-α in the systemic circulation. Furthermore, evidence of Th1-type immune polarization was observed as a result of increase in IL-12/23 p40 cytokine concentrations 72 hours post-virus administration. Our observations suggest that HP-NAP can serve as a potent immunomodulator in promoting anti-tumor immune response in the tumor microenvironment and enhance the therapeutic effect of oncolytic adenovirus.
  • Rönnblom, Anders, et al. (författare)
  • Celiac disease, collagenous sprue and microscopic colitis in IBD. Observations from a population-based cohort of IBD (ICURE)
  • 2015
  • Ingår i: Scandinavian Journal of Gastroenterology. - 0036-5521 .- 1502-7708. ; 50:10, s. 1234-1240
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective. Inflammatory bowel disease (IBD), microscopic colitis and celiac disease are all diseases with worldwide distribution and increased incidence has been reported from many areas. There is a shortage of studies investigating the occurrence of these diseases in the same individual and whether those affected demonstrate any particular phenotype. The aim of the study was to describe the concomitant incidence of microscopic colitis and celiac disease in a population-based IBD cohort. Methods. All 790 individuals in a prospective population-based cohort included 2005-09 from Uppsala region, Sweden, were reviewed regarding the appearance of microscopic or celiac disease before or after IBD diagnosis. Results. Fifty percent (396/790) of the patients had been examined for the possibility of celiac disease. Seventeen patients with celiac disease were found, representing 2.2% of the cohort. Patients with celiac disease were younger compared to the non-celiac patients and those with colitis had more often an extensive inflammation of the colon. Seventy-one percent (12/17) were women. The majority of the patients were diagnosed with celiac disease before IBD. Five patients with IBD had an earlier diagnosis of microscopic colitis or developed it after the IBD diagnosis. One teenager developed collagenous sprue, misinterpreted as a severe relapse of ulcerative colitis (UC) resulting in colectomy. Conclusions. The risk for celiac disease seems not to be increased in IBD, but those affected by both diseases seem to be predominantly women with extensive UC. There is a potential association between microscopic colitis and IBD.
  • Sangfelt, Per, et al. (författare)
  • Monitoring Dominant Strictures in Primary Sclerosing Cholangitis with Brush Cytology and FDG-PET
  • 2014
  • Ingår i: Journal of Hepatology. - 0168-8278 .- 1600-0641. ; 61:6, s. 1352-1357
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND/AIMS: Despite high risk of cholangiocellular adenocarcinoma (CCA) it is unclear how surveillance of patients with primary sclerosing cholangitis (PSC) should be performed.METHOD: We evaluated a follow-up algorithm of brush cytology and positron emission tomography/computed tomography with [18F]fluorodeoxyglucose ([18F]FDG-PET/CT), measured as the maximum standardized uptake values normalized to the liver background (SUVmax/liver) at 180 minutes, in PSC patients with dominant bile duct strictures.RESULTS: Brush cytology with high grade dysplasia (HGD) was detected in 12/70 patients (17%), yielding diagnostic sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 56%, 89%, 75% and 88%, respectively. Preemptive liver transplantations due to repeated HGD before manifest CCA were performed in six patients. Receiver operating characteristic (ROC) analysis of [18F]FDG uptake showed that a SUVmax/liver quotient of 3.3 was able to discriminate between CCA and non-malignant disease with a sensitivity, specificity, PPV and NPV for CCA of 89%, 92%, 62%, 98%, respectively. A SUVmax/liver >3.3 detected CCA in 8/9 patients whereas a quotient < 2.4 excluded CCA. Combining brush cytology and quantitative [18F]FDG-PET/CT yielded a sensitivity for HGD and/or CCA of 100% and a specificity of 88%.CONCLUSION: Early detection of HGD before manifest CCA is feasible with repeated brush cytology and may allow for preemptive liver transplantation. [18F]FDG-PET/CT has a high sensitivity for manifest CCA and a negative scan indicates a non-malignant state of the disease. Brush cytology and [18F]FDG-PET/CT are complementary in monitoring and managing PSC patients with dominant strictures.
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  • Föregående 12[3]45Nästa
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