Nijmegen, Netherlands
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Van den Ouweland J.M.W.,Canisius Wilhelmina Hospital | Kema I.P.,University of Groningen
Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences | Year: 2012

Liquid chromatography coupled to mass spectrometry (LC-MS/MS) is increasingly used as a routine methodology in clinical laboratories for the analysis of low molecular weight molecules. The high specificity in combination with high sensitivity and multi-analyte potential makes it an attractive complementary method to traditional methodology used for routine applications. Its strength and weaknesses in this context will be discussed and examples of successful clinical applications will be given. For LC-MS/MS to truly fulfil its promise in clinical diagnosis, the prerequisite steps being sample pre-treatment, chromatographic separation and detection by selected reaction monitoring must become more integrated as they are in conventional clinical analysers. The availability of ready-to-use reagents kits, eliminating efforts needed for method development and extensive validation, are likely to contribute to a wider acceptance of LC-MS/MS in clinical laboratories. Growing applicability of LC-MS/MS in the clinical laboratory field is expected from quantitative protein analysis. © 2011 Elsevier B.V..


Dings P.J.M.,Radboud University Nijmegen | Elferink M.A.G.,Comprehensive Cancer Center the Netherlands | Strobbe L.J.A.,Canisius Wilhelmina Hospital | De Wilt J.H.W.,Radboud University Nijmegen
Annals of Surgical Oncology | Year: 2013

Background: The absolute number of involved axillary lymph nodes (LNs) is considered the most important prognostic factor in breast cancer. Over the last decade, several studies indicated that the lymph node ratio (LNR) might predict outcome better than the number of positive LNs. In this study we test the applicability of earlier published LNR cutoff values and study the prognostic value of the LNR on a nationwide level. Methods: A nationwide population-based study was performed, using data from the Netherlands Cancer Registry, including all women diagnosed with node-positive breast cancer between 1999 and 2005 (N = 25,315). Patients were divided into 3 LNR risk groups (low, ≤0.20; intermediate, 0.21-0.65; and high, >0.65). Kaplan-Meier survival analysis was performed. In order to evaluate whether LNR was associated with overall survival (OS), Cox proportional hazards modeling was used. Results: For the entire cohort, 5- and 10-year OS rates were 78 % and 62 %, respectively. The number of positive LNs correlated with OS (5-year OS 84 %, 72 %, and 55 % for patients with 1-3, 4-9, and 10 or more positive LNs, respectively, P <.001). LNR also correlated with OS (5-year OS 86 %, 75 %, and 54 % for low-, intermediate-, and high-risk groups, respectively, P <.001). In the multivariable analysis, the risk of death increased with increasing LNR (P <.001). Conclusions: The LNR has an important prognostic value in node-positive patients, independent of traditional clinicopathological factors. LNR should be added as an independent prognostic variable to the current staging system. © 2013 Society of Surgical Oncology.


Amgen's new drug was found capable of shrinking artery-clogging plaques when used with cholesterol-lowering statin, results of a new clinical trial have shown. The combination of the drug Repatha (evolocumab) and statin also reduced LDL, also known as bad cholesterol, to extremely low levels in a majority of high-risk heart patients after a treatment period of 18 months. In the trial reported in the Journal of the American Medical Association on Tuesday, Nov. 15, Cleveland Clinic head of cardiology Dr. Steven Nissen and colleagues compared the effect of monthly injections with Repatha with statin therapy and statins alone on plaques that can cause heart attack. The nearly 1,000 participants of the study were patients with symptomatic heart disease and had blockages of between 20 and 50 percent in tested arteries. Nissen and colleagues collected the measurements of the plaque at the start of the trial and 18 months after using an ultrasound probe placed inside the diseased artery. In patients who received only statin, bad cholesterol remained at around 93 but the average level dropped to 36.6 in patients who used both Repatha and statin. Artery plaque likewise stayed about the same in those who received only statin but shrank 1 percent in those who received both drugs. In some participants who experienced more dramatic reduction in LDL levels, plaque shrank by 2 percent. "Among patients with angiographic coronary artery disease treated with statins, addition of subcutaneous evolocumab, compared with placebo, resulted in a greater decrease in percent atheroma volume after 76 weeks of treatment," researchers wrote in their study. Bigger studies are to see if the drops in cholesterol level can lead to fewer heart attacks and even deaths. Based on the plaque regression data from the study presented on Tuesday, however, investigators think that these trials will be positive. "These findings suggest that the large clinical outcome trials currently underway are likely to show major benefits," said one of study's lead directors Dr. Stephen Nicholls from Canisius Wilhelmina Hospital in the Netherlands. Although the result of the trial is promising, use of Amgen's new drug has its drawback. Statins are pills and they are sold at a cheap price. Repatha on the other hand must be given as shots twice or once a month using a pen-like device. The new drug, which belongs to a new class of drugs known as PCSK9 inhibitors, is also far more expensive, costing $14,000 a year and insurers do not often pay. © 2017 Tech Times, All rights reserved. Do not reproduce without permission.


Janssen J.P.,Canisius Wilhelmina Hospital
European Respiratory Review | Year: 2010

Thoracoscopy is an old but still very valuable technique for the evaluation of pleural pathology and, especially for the further investigation of the aetiology of pleural fluid. It remains of great importance, since it is able to not only provide an exact diagnosis, but also can have therapeutic potential. In this review, the differential diagnostic aspects of transudate versus exudate are further elaborated, and the role of thoracoscopy is compared to closed pleural biopsy and image guided biopsy. © ERS 2010.


Snoeck M.,Canisius Wilhelmina Hospital
Local and Regional Anesthesia | Year: 2012

Articaine is an intermediate-potency, short-acting amide local anesthetic with a fast metabolism due to an ester group in its structure. It is effective with local infiltration or peripheral nerve block in dentistry, when administered as a spinal, epidural, ocular, or regional nerve block, or when injected intravenously for regional anesthesia. In comparative trials, its clinical effects were not generally significantly different from those of other short-acting local anesthetics like lidocaine, prilocaine, and chloroprocaine, and there is no conclusive evidence demonstrating above-average neurotoxicity. Articaine proved to be suitable and safe for procedures requiring a short duration of action in which a fast onset of anesthesia is desired, eg, dental procedures and ambulatory spinal anesthesia, in normal and in special populations. © 2012 Snoeck, publisher and licensee Dove Medical Press Ltd.


Hermans D.J.J.,Radboud University Nijmegen | Bauland C.G.,Canisius Wilhelmina Hospital | Zweegers J.,Radboud University Nijmegen | Van Beynum I.M.,Erasmus Medical Center | Van Der Vleuten C.J.M.,Radboud University Nijmegen
British Journal of Dermatology | Year: 2013

Background Infantile haemangioma (IH) is a benign, common and self-limiting tumour of infancy; only a minority of cases need active treatment. Currently, propranolol appears superior to classic treatments. Objectives To document in a prospective study indications and side-effects of propranolol for complicated IH in a large patient group. Methods Analysis of prospectively collected data was performed on 174 patients with IH treated with propranolol in a tertiary referral centre from September 2008 to January 2012. Results The group consisted of children with a potentially threatening and/or complicated IH; the girl/boy ratio was 123/51, and the mean age at the start of treatment was 4·8 months. In 173 cases (99·4%), treatment was successful, as assessed nonquantitatively by clinical observation. This striking effect was characterized by immediate cessation of growth, softening, fading of the erythema and rapid induction of regression. The mean duration of treatment was 10·7 months. The most important adverse effects were hypotension (3·4%), wheezing (9·2%), nocturnal restlessness (22·4%) and cold extremities (36·2%). In one patient, propranolol was stopped. In 15 patients it was necessary to reduce the dose, although the lower dose was still effective. Conclusions In this study, propranolol was effective and safe in almost all patients with complex IH. Administration of systemic medication to an infant with a benign condition requires careful consideration, as only a minority of patients with IH require an active medical intervention. A shift of the indication of propranolol for IH is evident, expanding its application for life-threatening situations or severe functional impairment to early prevention of disfigurement or cosmetically permanent sequelae. However, the indication for such an active approach should be determined by experienced physicians. © 2012 The Authors. BJD © 2012 British Association of Dermatologists.


Chowdhary A.,University of Delhi | Sharma C.,University of Delhi | Hagen F.,Canisius Wilhelmina Hospital | Meis J.F.,Canisius Wilhelmina Hospital | Meis J.F.,Radboud University Nijmegen
Future Microbiology | Year: 2014

Aspergillus fumigatus, a ubiquitously distributed opportunistic pathogen, is the global leading cause of aspergillosis. Azole antifungals play an important role in the management of aspergillosis. However, over a decade, azole resistance in A. fumigatus isolates has been increasingly reported with variable prevalence worldwide and it is challenging the effective management of aspergillosis. The high mortality rates observed in patients with invasive aspergillosis caused by azole-resistant A. fumigatus (ARAF) isolates pose serious challenges to the clinical microbiologist for timely identification of resistance and appropriate therapeutic interventions. The majority of ARAF isolates contain alterations in the cyp51A gene; however, there have been increasing reports on non-cyp51A mutations contributing to azole resistant phenotypes. This review highlights the emergence and various mechanisms implicated in the development of azole resistance in A. fumigatus. We further present recent developments related to the environmental route in the emergence of ARAF isolates and discuss the therapeutic options available. © 2014 Future Medicine Ltd.


Bartels R.H.M.A.,Radboud University Nijmegen | Donk R.,Canisius Wilhelmina Hospital | Verbeek A.L.M.,Radboud University Nijmegen
Neurosurgery | Year: 2010

Objective: A meta-analysis was performed to evaluate whether a beneficial clinical effect of cervical disk prostheses over conventional cervical diskectomy with fusion exists. Methods: A literature search was completed ending February 4, 2009, that included the abstract books of recent major spine congresses. All studies reported the results of single-level cervical disease without myelopathy. The Visual Analog Score (VAS) of the arm, VAS of the neck, Neck Disability Index, Physical Composite Scores of the Short Form 36, and Mental Composite Score of the Short Form 36, as well as adverse events, were evaluated. Results: Nine records were found, totaling 1533 patients. Of these, 1165 were evaluable at the last follow-up at 12 or 24 months. As an effect measure, a pooled odds ratio (OR) was calculated at 12 and 24 months. At 12 months, the VAS arm reached statistical significance (OR = 0.698; 95% confidence interval [CI], 0.571-0.853), as did the VAS neck (OR = 0.690; 95% CI, 0.562-0.847), and the Physical Composite Scores (OR = 1.362; 95% CI, 1.103-1.682) and the Mental Composite Score (OR = 1.270; 95% CI, 1.029-1.569) of the Short Form 36, favoring arthroplasty. The Neck Disability Index at 24 months also reached statistical difference (OR = 0.794; 95% CI, 0.641-0.984). All other measurements did not reveal any statistical difference. The number of complications, including secondary surgeries for adjacent segment disease, did not differ. Conclusion: A clinical benefit for the cervical disk prosthesis is not proven. Because none of the studies were blinded, bias of the patient or researcher is a probable explanation for the differences found. Therefore, these costly devices should not be used in daily clinical practice. Copyright © 2010 by the Congress of Neurological Surgeons.


Venhovens J.,Canisius Wilhelmina Hospital | Meulstee J.,Canisius Wilhelmina Hospital | Verhagen W.I.M.,Canisius Wilhelmina Hospital
Clinical Neurophysiology | Year: 2016

Several types of acoustic stimulation (i.e. tone bursts or clicks), bone-conducted vibration, forehead taps, and galvanic stimulation elicit myogenic potentials. These can be recorded in cervical and ocular muscles, the so called vestibular evoked myogenic potentials (VEMPs). The cervical VEMP (cVEMP) resembles the vestibulo-collic reflex and the responses can be recorded from the ipsilateral sternocleidomastoid muscle. The ocular VEMP resembles the vestibulo-ocular reflex and can be recorded from extra-ocular muscles by a surface electrode beneath the contralateral infraorbital margin. Initially, the literature concerning VEMPs was limited to peripheral vestibular disorders, however, the field of VEMP testing is rapidly expanding, with an increasing focus on central neurological disorders. The current literature concerning VEMP abnormalities in central neurological disorders is critically reviewed, especially regarding the methodological aspects in relation to quality as well as the clinical interpretation of the VEMP results. Suggestions for further research are proposed as well as some clinically useful indications. © 2015 International Federation of Clinical Neurophysiology.


Van Den Ouweland J.M.W.,Canisius Wilhelmina Hospital | Vogeser M.,Ludwig Maximilians University of Munich | Bacher S.,Ludwig Maximilians University of Munich
Reviews in Endocrine and Metabolic Disorders | Year: 2013

The prevalence of vitamin D deficiency in the general population has become a major public health problem. Vitamin D deficiency might have significant consequences not only to bone health but possibly to autoimmune-, infectious and cardiovascular disease. This has resulted in increased clinical testing for 25-hydroxyvitamin D (25(OH)D) in serum, as circulating 25(OH)D is regarded as the best indicator of adequate exposure to sunlight and dietary intake of vitamin D. There are reportedly over 50 vitamin D metabolites of which 25(OH)D and 1,25(OH)2D are well known to provide clinical information. More recently, there is increasing interest in measuring the C3-epimer of 25(OH)D, which has shown to contribute significantly to the 25(OH)D concentration, particularly in infant populations, and in 24,25(OH)2D, a major catabolite of 25(OH)D metabolism. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is an analytical tool that allows the specific determination of all relevant vitamin D metabolites, with the potential of performing multiple analyte analysis in a single experimental setting, creating a vitamin D profile. This article reviews recent advances in the quantification of vitamin D metabolites using LC-MS/MS. © 2013 Springer Science+Business Media New York.

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