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Vejle, Denmark

Overgaard M.,University of Southern Denmark | Brasen C.L.,University of Southern Denmark | Svaneby D.,Vejle Sygehus | Feddersen S.,University of Southern Denmark | Nybo M.,University of Southern Denmark
Annals of Clinical Biochemistry | Year: 2013

Familial lipoprotein lipase (LPL) deficiency (FLLD) is a rare autosomal recessive genetic disorder caused by homozygous or compound heterozygous mutations in the LPL gene. FLLD individuals usually express an impaired or non-functional LPL enzyme with low or absent triglyceride (TG) hydrolysis activity causing severe hypertriglyceridaemia. Here we report a case of FLLD in a 29-year-old man, who initially presented with eruptive cutaneous xanthomata, elevated plasma TG concentration but no other co-morbidities. Subsequent genetic testing of the patient revealed compound heterozygosity of a novel duplication (p.R44Kfs*4) leading to a premature stop codon in exon 2 and a known mutation (N291S) in exon 5 of the LPL gene. Further biochemical analysis of the patient's postheparin plasma confirmed a reduction of total lipase activity compared with his heterozygous father carrying the common N291S mutation and to a healthy control. Also the patient showed increased (1.85-fold) activity of hepatic lipase (HL), indicating a functional link between HL and LPL. In summary, we report a case of FLLD caused by compound heterozygosity of a new duplication and a common mutation in the LPL gene, resulting in residual LPL activity. With such mutations, individuals may not receive a diagnosis before classical FLLD symptoms appear later in adulthood. Nevertheless, early diagnosis and lipid-lowering treatment may favour a reduced risk of premature cardiovascular disease or acute pancreatitis in such individuals. © The Author(s) 2013. Source

Klitgaard J.L.,Symphogen | Klitgaard J.L.,Dana-Farber Cancer Institute | Koefoed K.,Symphogen | Geisler C.,Rigshospitalet | And 7 more authors.
British Journal of Haematology | Year: 2013

Summary: The treatment of chronic lymphocytic leukaemia (CLL) has been improved by introduction of monoclonal antibodies (mAbs) that exert their effect through secondary effector mechanisms. CLL cells are characterized by expression of CD5 and CD23 along with CD19 and CD20, hence anti-CD5 Abs that engage secondary effector functions represent an attractive opportunity for CLL treatment. Here, a repertoire of mAbs against human CD5 was generated and tested for ability to induce complement-dependent cytotoxicity (CDC) and antibody-dependent cell-mediated cytotoxicity (ADCC) both as single mAbs and combinations of two mAbs against non-overlapping epitopes on human CD5. The results demonstrated that combinations of two mAbs significantly increased the level of CDC compared to the single mAbs, while no enhancement of ADCC was seen with anti-CD5 mAb combinations. High levels of CDC and ADCC correlated with low levels of Ab-induced CD5 internalization and degradation. Importantly, an anti-CD5 mAb combination enhanced CDC of CLL cells when combined with the anti-CD20 mAbs rituximab and ofatumumab as well as with the anti-CD52 mAb alemtuzumab. These results suggest that an anti-CD5 mAb combination inducing CDC and ADCC may be effective alone, in combination with mAbs against other targets or combined with chemotherapy for CLL and other CD5-expressing haematological or lymphoid malignancies. © 2013 John Wiley & Sons Ltd. Source

Miehlke S.,Center for Digestive Diseases Eppendorf | Madisch A.,Siloah Hospital | Kupcinskas L.,Lithuanian University of Health Sciences | Petrauskas D.,Lithuanian University of Health Sciences | And 9 more authors.
Gastroenterology | Year: 2014

Background & Aims Studies reporting that budesonide is effective for the treatment of collagenous colitis have been small and differed in efficacy measures. Mesalamine has been proposed as a treatment option for collagenous colitis, although its efficacy has never been investigated in placebo-controlled trials. We performed a phase 3, placebo-controlled, multicenter study to evaluate budesonide and mesalamine as short-term treatments for collagenous colitis. Methods Patients with active collagenous colitis were randomly assigned to groups given pH-modified release oral budesonide capsules (9 mg budesonide once daily, Budenofalk, n = 30), mesalamine granules (3 g mesalamine once daily, Salofalk, n = 25), or placebo for 8 weeks (n = 37) in a double-blind, double-dummy fashion. The study was conducted in 31 centers (hospital clinics and private practices) in Germany, Denmark, Lithuania, Spain, and the United Kingdom. The primary end point was clinical remission at 8 weeks defined as ≤3 stools per day. Secondary end points included clinical remission at 8 weeks, according to the Hjortswang-Criteria of disease activity, taking stool consistency into account. Results A greater percentage of patients in the budesonide group were in clinical remission at week 8 than the placebo group (intention-to-treat analysis, 80.0% vs 59.5%; P =.072; per-protocol analysis, 84.8% vs 60.6%; P =.046). Based on the Hjortswang-Criteria, 80.0% of patients given budesonide achieved clinical remission compared with 37.8% of patients given placebo (P =.0006); 44.0% of patients given mesalamine achieved clinical remission, but budesonide was superior to mesalamine (P =.0035). Budesonide significantly improved stool consistency and mucosal histology, and alleviated abdominal pain. The rate of adverse events did not differ among groups. Conclusions Oral budesonide (9 mg once daily) is effective and safe for short-term treatment of collagenous colitis. Short-term treatment with oral mesalamine (3 g once daily) appears to be ineffective. ClinicalTrials.gov number, NCT00450086. Source

Diez P.,Mount Vernon Center for Cancer Treatment | Vogelius I.S.,Vejle Sygehus | Vogelius I.S.,University of Wisconsin - Madison | Bentzen S.M.,University of Wisconsin - Madison
International Journal of Radiation Oncology Biology Physics | Year: 2010

Purpose: A new method is presented for synthesizing dose-response data for biochemical control of prostate cancer according to study design (randomized vs. nonrandomized) and risk group (low vs. intermediate-high). Methods and Materials: Nine published prostate cancer dose escalation studies including 6,539 patients were identified in the MEDLINE and CINAHL databases and reviewed to assess the relationship between dose and biochemical control. A novel method of analysis is presented in which the normalized dose-response gradient, γ50, is estimated for each study and subsequently synthesized across studies. Our method does not assume that biochemical control rates are directly comparable between studies. Results: Nonrandomized studies produced a statistically significantly higher γ50 than randomized studies for intermediate- to high-risk patients (γ50 = 1.63 vs. γ50 = 0.93, p = 0.03) and a borderline significantly higher (γ50 = 1.78 vs. γ50 = 0.56, p = 0.08) for low-risk patients. No statistically significant difference in γ50 was found between low- and intermediate- to high-risk patients (p = 0.31). From the pooled data of low and intermediate- to high-risk patients in randomized trials, we obtain the overall best estimate of γ50 = 0.84 with 95% confidence interval 0.54-1.15. Conclusions: Nonrandomized studies overestimate the steepness of the dose-response curve as compared with randomized trials. This is probably the result of stage migration, improved treatment techniques, and a shorter follow-up in higher dose patients that were typically entered more recently. This overestimation leads to inflated expectations regarding the benefit from dose-escalation and could lead to underpowered clinical trials. There is no evidence of a steeper dose response for intermediate- to high-risk compared with low-risk patients. © 2010 Elsevier Inc. All rights reserved. Source

Appelt A.L.,Vejle Sygehus | Appelt A.L.,University of Southern Denmark | Vogelius I.R.,Copenhagen University
Radiotherapy and Oncology | Year: 2012

Several clinical risk factors for radiation induced toxicity have been identified in the literature. Here, we present a method to quantify the effect of clinical risk factors on radiation dose-response curves and apply the method to adjust the dose-response for radiation pneumonitis for patients with/without pre-existing pulmonary co-morbidities. © 2011 Elsevier Ireland Ltd. All rights reserved. Source

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