Detlefsen S.,Vejle Hospital |
Detlefsen S.,University of Southern Denmark
Histology and Histopathology | Year: 2013
During the first decade of the 21st century, IgG4-related disease (IgG4-RD), a fibroinflammatory condition occurring at multiple sites of the body, has been newly recognized. As indicated by its name, elevation of IgG4 in the serum and tissue is a common denominator of IgG4-RD. Since the observation that many patients suffering from autoimmune pancreatitis (AIP), a specific type of chronic pancreatitis, had elevated serum levels of IgG4, it was reported that these patients also had increased numbers of IgG4-positive cells in the inflamed pancreatic tissue. In 2003, it was noted that a significant proportion of the AIP patients had a variety of extrapancreatic fibroinflammatory lesions, and that AIP therefore was the pancreatic manifestation of a systemic disease. Among these extrapancreatic manifestations, the extrahepatic bile ducts, salivary glands, thyroid, lymph nodes and retroperitoneum were most frequently reported, and infiltration of the tissue with IgG4-positive cells was also noted at these sites. During the following years, a multitude of other conditions have been added to the spectrum of IgG4-RD. While some of these organ manifestations were once believed to represent diseases on their own, others have been included under the umbrella of multifocal fibrosclerosis. Biopsies or resection specimens from affected organs in IgG4-RD reveal several common microscopic features irrespective of the site of the lesion. Cellular and storiform fibrosis, lymphoplasmacytic infiltration, increased numbers of IgG4-positive cells and obliterative phlebitis are among the most characteristic histological changes in IgG4-RD. The detailed etiology, pathophysiology, epidemiology and clinical long-term outcome have at present yet to be fully elucidated. This paper focuses on the microscopic features, diagnosis and differential diagnosis of the different organ manifestations of IgG4-RD, and the current concepts of its pathogenesis will also be addressed.
Christensen H.,Vejle Hospital
Telemedicine journal and e-health : the official journal of the American Telemedicine Association | Year: 2011
We have developed an expert computer system for the control of oral anticoagulation therapy, accessible by the patients via their own computer. To investigate if the weekly measurement and dosing of international normalized ratio (INR) at home using the online Internet-based system was superior to conventional treatment, we performed a randomized, controlled trial. All 669 patients in our anticoagulation clinic were asked to participate in the trial, providing that they had Internet access and could use the CoaguChek XS system. A total of 140 patients were included and randomized to (A) once weekly measurement and report online, (B) twice weekly measurement and report online, and (C) continued conventional treatment with INR measurement in the lab every 4 weeks and dose adjustment by letter. Group A had 79.7% (95% CI 79.0-80.3) of time in therapeutic range (TTR), group B 80.2% (95% CI 79.4-80.9) of TTR, and group C 72.7% (95% CI 71.9-73.4) TTR. Groups A and B perform statistically significantly better than the conventional group C, with a difference of TTR of 7% points (p<2.2×10(-16)), whereas no difference was seen between A and B. Home measurement of INR and the reporting and dosing of results online once a week increase TTR from 72% to 79% as compared to conventional computer-assisted monitoring in an anticoagulation clinic.
Groth K.A.,Aarhus University Hospital |
Skakkebaek A.,Aarhus University Hospital |
Host C.,Aarhus University Hospital |
Gravholt C.H.,Aarhus University Hospital |
Bojesen A.,Vejle Hospital
Journal of Clinical Endocrinology and Metabolism | Year: 2013
Context: Recently, new clinically important information regarding Klinefelter syndrome (KS) has been published. We review aspects of epidemiology, endocrinology, metabolism, body composition, and neuropsychology with reference to recent genetic discoveries. Evidence Acquisition: PubMed was searched for "Klinefelter," "Klinefelter's," and "XXY" in titles and abstracts. Relevant papers were obtained and reviewed, as well as other articles selected by the authors. Evidence Synthesis: KS is the most common sex chromosome disorder in males, affecting one in 660 men. The genetic background is the extra X-chromosome, which may be inherited from either parent. Most genes from the extra X undergo inactivation, but some escape and serve as the putative genetic cause of the syndrome. KS is severely underdiagnosed or is diagnosed late in life, roughly 25% are diagnosed, and the mean age of diagnosis is in the mid-30s. KS is associated with an increased morbidity resulting in loss of approximately 2 yr in life span with an increased mortality from many different diseases. The key findings in KS are small testes, hypergonadotropic hypogonadism, and cognitive impairment. The hypogonadism may lead to changes in body composition and a risk of developing metabolic syndrome and type 2 diabetes. The cognitive impairmentis mainly in the area of language processing. Boys with KS are often in need of speech therapy, and many suffer from learning disability and may benefit from special education. Medical treatment is mainly testosterone replacement therapy to alleviate acute and long-term consequences of hypogonadism as well as treating or preventing the frequent comorbidity. Conclusions: More emphasis should be placed on increasing the rate of diagnosis and generating evidence for timing and dose of testosterone replacement. Treatment of KS should be a multidisciplinary task including pediatricians, speech therapists, general practitioners, psychologists, infertility specialists, urologists, and endocrinologists. Copyright © 2013 by The Endocrine Society.
Hansen L.K.,Vejle Hospital
Danish medical journal | Year: 2014
Ulcerative Colitis (UC) is a chronic inflammatory bowel disease located in the mucosa of the large bowel. UC often affects young adults between 15 and 40 years of age with no pre-dominant sex. Over time, incidence rates are steadily increasing and the cause of the disease remains unknown. Symptoms are general discomfort and bloody diarrhea. UC is diagnosed by endoscopic examination of the large bowel, where different hallmarks are found. It is of great importance that attacks/relapses are treated medically, as flares may cause death due to inflammatory destruction of the mucosa and perforation of the colon leading to extreme infection of the abdominal cavity. UC often affects the social life of the patients, as they feel that they must be in the immediate vicinity of toilets. Therefore, many patients prefer to stay at home during active disease. For society, UC is a costly disease due to patients reporting in sick and expensive medications. When medical treatment fails, UC patients must undergo surgery and have their colon removed (colectomy). This PhD project focused on the immune system of the body. Specifically, we looked into T cells (the chairmen of the immune system) that we believe play an important role in disease activity. When T cells are activated in inflammatory diseases, they produce several signaling substances (cytokines) that attract and activate the other parts of the immune system. T cells regulate their effector functions through calcium regulation. Upon activation, calcium is released from intracellular stores, which causes calcium channels to be embedded in the cell membrane (CRAC channels). As long as the T cells are stimulated, the two potassium channels KV1.3 and KCa3.1 maintain the driving force for calcium influx, thus keeping the T cells activated. Our aims were to investigate whether the two potassium channels KV1.3 and KCa3.1 were upregulated in mucosal biopsies from patients with active UC and whether there were correlations between the expression of the channels and the disease severity assessed by endoscopic and histological evaluation. Moreover, we used a rat colitis model (dextran sodium sulphate-induced) to examine the effect of pharmacological inhibition of KV1.3 and KCa3.1 on inflammation. We found that the expression of T cell potassium channel, KV1.3, was increased in active UC and a higher expression correlated well with both the endoscopic and the histological degree of inflammation. This suggests KV1.3 to be involved in the inflammatory process of UC. We did not find an increase of the other potassium channel, KCa3.1, at the gene expression level, but the channels were definitely present in the infiltrating T cells as examined by immunostaining. Preliminary gene expression data showed similar changes of gene expression in biopsies from Crohns disease (CD) patients. In addition, we conducted first pilot studies investigating whether pharmacological blockade of the channels ameliorates colitis in the rat DSS-model. We found a tendency towards less endoscopic inflammation in the acute phase (at day 7 and 10). However, at study termination, the improvement of inflammation failed to reach a significant level, presumably because of insufficient compound absorption from the intestine (based on low plasma concentration and previously reported amelioration of colitis by inhibiting KCa3.1). Based on these findings in our target identification study, it is suggested that both KV1.3 and KCa3.1 play a role in the inflammation of UC and possibly of CD and represent new pharmacological targets.
Gimsing S.,Vejle Hospital
Journal of Laryngology and Otology | Year: 2010
Objectives: (1) To compare audiometric parameters in patients with vestibular schwannoma and in those with asymmetric hearing loss from other causes; and (2) to assess proposed screening criteria by comparing published protocols. Methods: Audiometric data from 199 vestibular schwannoma patients and 225 non-tumour patients were compared. Eight screening protocols were tested on these 424 patients. Results: Vestibular schwannoma and non-tumour patients with little or no hearing loss in the unaffected ear were inseparable; however, vestibular schwannoma patients with hearing loss in the unaffected ear had greater audiometric asymmetry, compared with non-tumour patients with the same pattern of hearing loss. The sensitivity of screening protocols varied from 73 to 100 per cent; parallelism was observed between sensitivity and screening rate. Conclusion: As regards vestibular schwannoma screening protocols, the best compromise between sensitivity and screening rate was offered by a criterion comprising either: (1) 20dB asymmetry at two neighbouring frequencies, or unilateral tinnitus, or (2) 15dB asymmetry at two frequencies between 2 and 8kHz. Copyright © JLO (1984) Limited 2009.