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Abbes Orabi N.,St Luc University Hospital | Vanwymersch T.,St Luc University Hospital | Paterson H.M.,St Luc University Hospital | Mauel E.,St Luc University Hospital | And 3 more authors.
Colorectal Disease | Year: 2011

Aim This study aimed to assess long-term function after total perineal reconstruction (TPR) with dynamic graciloplasty (DG) and systematic Malone appendicostomy (MA) adjunction after abdominoperineal excision (APR) for rectal cancer. Method From 1999 to 2004, TPR using DG and MA was performed in 10 patients [seven women; median age 40(range 28-55)years] after APR for rectal cancer (cT2 in one patient, cT3 in six patients and cT4 in three patients). We prospectively recorded early and late morbidity, mortality, oncological outcome, functional results (using the modified Working Party on Anal Sphincter Replacement 'WPASR' scoring system) and quality of life (QoL; using the European Organisation for Research and Treatment of Cancer 'EORTC' QLQ-C30 and QLQ-CR38 questionnaires). Results There was no procedure-related mortality. One patient required intra-abdominal re-operation. Nine patients required local and multiple revisions [there was one coloperineal anastomosis (CPA) stenosis, five CPA mucosal prolapse, three stenosis related to graciloplasty, two MA stenosis and one MA reflux]. After a median follow up of 78months, there was no local recurrence and six patients were alive and disease-free. Regarding the functional results, the median modified WPASR score, of 8, after a follow up of 78months, was good. The overall QoL scores remained stable over time. Conclusion In carefully selected patients who want to avoid definitive abdominal colostomy after APR for rectal cancer, reconstruction involving MA and DG after APR for low rectal cancer is followed by good long-term function and QoL. © 2011 The Authors. Colorectal Disease © 2011 The Association of Coloproctology of Great Britain and Ireland. Source

Laloux P.,Mont Godinne University Hospital | Lemonnier F.,Mont Godinne University Hospital | Jamart J.,Catholic University of Louvain
Acta Neurologica Belgica | Year: 2010

The profile of recurrent ischemic strokes has not been much investigated. The aim of this study was to evaluate how the therapeutic strategies recommended for secondary prevention after an ischemic stroke are implemented in the real world of clinical practice. All patients admitted for a recurrent ischemic stroke or TIA were prospectively registered. The etiology was determined according to the TOAST classification. The risk factors and cardiovascular treatment at the time of the recurrence were recorded. A total of 168 patients were evaluated. Most of the patients (61%) recurred after 1 year. The recurrent stroke was not associated with a particular etiological subtype. The most frequent risk factor was hypertension (79%), followed by hypercholesterolemia (43%), smoking (25%), and diabetes (22%). Most of the patients had more than 1 risk factor (84%). Hypertension was not satisfactorily controlled in 38% of patients, hypercholesterolemia in 42%, and diabetes in 59%. A significant minority of patients (15%) were not taking any antithrombotic agent despite a history of stroke or TIA. Only 34% of the cases with a known atrial fibrillation were on anticoagulant therapy and the International Normalized Ratio was <2.0 in 71% of them. In conclusion, stroke prevention needs to be improved by better implementation of therapeutic strategies in clinical practice. The patients should also be better informed about target values as well as the importance of physical activity and smoking cessation. Source

Hasdenteufel F.,Allergy Therapeutics | Luyasu S.,Mont Godinne University Hospital | Hougardy N.,Clinic of South Luxembourg | Fisher M.,University of Sydney | And 3 more authors.
Current Clinical Pharmacology | Year: 2012

Structure-activity relationships (SARs) refer to the relation between chemical structure and pharmacologic activity for a series of compounds. Since the pioneering work of Crum-Brown and Fraser in 1868, they have been increasingly used in the pharmaceutical, chemical and cosmetic industries, especially for drug and chemical design purposes. Structure-activity relationships may be based on various techniques, ranging from considerations of similarity or diversity of molecules to mathematical relationships linking chemical structures to measured activities, the latter being referred to as quantitative SAR or QSAR. This review aims at briefly reviewing the history of SARs and highlighting their interest in delayed and immediate drug allergy using selected examples from the literature. Studies of SAR are commonly conducted in the area of contact dermatitis, a delayed hypersensitivity reaction, to determine the allergenic potential of a given compound without animal testing. In immediate, immunoglobulin E-mediated drug hypersensitivity, this kind of approach remains rather confidential. It has been mainly applied to neuromuscular blocking drugs (muscle relaxants) and betalactam antibiotics (penicillins, cephalosporins). This review shows that SARs can prove useful to (i) predict the allergenic potential of a chemical or a drug, (ii) help identify putative antigenic determinants for each patient or small group of patients sharing the same cross-reactivity pattern, and (iii) predict the likelihood of adverse reactions to related molecules and select safe alternatives. © 2012 Bentham Science Publishers. Source

Al Assaf C.,Catholic University of Leuven | Van Obbergh F.,Catholic University of Leuven | Billiet J.,Laboratory of Hematology | Lierman E.,Catholic University of Leuven | And 10 more authors.
Haematologica | Year: 2015

The JAK2 V617F mutation, the thrombopoietin receptor MPL W515K/L mutation and calreticulin (CALR) mutations are mutually exclusive in essential thrombocythemia and support a novel molecular categorization of essential thrombocythemia. CALR mutations account for approximately 30% of cases of essential thrombocythemia. In a retrospective study, we examined the frequency of MPL and CALR mutations in JAK2 V617F-negative cases of essential thrombocythemia (n=103). In addition, we compared the clinical phenotype and outcome of CALR mutant cases of essential thrombocythemia with a cohort of JAK2 V617F-positive essential thrombocythemia (n=57). CALR-positive cases represented 63.7% of double-negative cases of essential thrombocythemia, and most carried CALR type 1 or type 2 indels. However, we also identified one patient who was positive for both the JAK2 V617F and the CALR mutations. This study revealed that CALR mutant essential thrombocythemia is associated with younger age, higher platelet counts, lower erythrocyte counts, leukocyte counts, hemoglobin, and hematocrit, and increased risk of progression to myelofibrosis in comparison with JAK2 V617F-positive essential thrombocythemia. Analysis of the CALR mutant group according to indel type showed that CALR type 1 deletion is strongly associated with male gender. CALR mutant patients had a better overall survival than JAK2 V617F-positive patients, in particular patients of age 60 years or younger. In conclusion, this study in a Belgian cohort of patients supports and extends the growing body of evidence that CALR mutant cases of essential thrombocythemia are phenotypically distinct from JAK2 V617F-positive cases, with regards to clinical and hematologic presentation as well as overall survival. © 2015 Ferrata Stor ti Foundation. Source

Ghardi M.,Belgian Nuclear Research Center | Moreels M.,Belgian Nuclear Research Center | Chatelain B.,Mont Godinne University Hospital | Chatelain C.,Mont Godinne University Hospital | Baatout S.,Belgian Nuclear Research Center
International Journal of Molecular Medicine | Year: 2012

In case of accidental radiation exposure or a nuclear incident, physical dosimetry is not always complete. Therefore, it is important to develop tools that allow dose estimates and determination that are based on biological markers of radiation exposure. Exposure to ionizing radiation triggers a large-scale activation of specific DNA signaling and repair mechanisms. This includes the phosphorylation of γH2AX in the vicinity of a double-strand break (DSB). A DNA DSB is a cytotoxic form of DNA damage, and if not correctly repaired can initiate genomic instability, chromosome aberrations, mutations or apoptosis. Measurements of DNA DSBs and their subsequent repair after in vitro irradiation has been suggested to be of potential use to monitor cellular responses. The bone marrow and the blood are known to be the most radiosensitive tissues of the human body and can therefore be of particular importance to find radiation-induced biological markers. In the present study, changes in H2AX phosphorylation and apoptosis of irradiated human peripheral blood mononuclear cells (PBMCs) were analyzed. Freshly isolated PBMCs from healthy donors were irradiated with X-rays (0.1, 0.25, 0.5, 1, 2 and 4 Gy). The phosphorylation of γH2AX was measured at different time points (0, 0.25, 1, 2, 4, 6 and 24 h) after irradiation. We detected a linear dose-dependency of γH2AX phosphorylation measured by γH2AX foci scoring using immunofluorescence microscopy as well as by γH2AX fluorescence detection using flow cytometry. Apoptosis was detected by measuring DNA fragmentation at different time points (0, 24, 48, 72, 96 h) after X-irradiation using DNA ladder gel electrophoresis. The apoptotic DNA fragmentation increased in a dose-dependent manner. In conclusion, DNA DSBs and subsequent apoptotic DNA fragmentation monitoring have potential as biomarkers for assessing human exposure in radiation biodosimetry. Source

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