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See detailSimultaneous determination of seven azole antifungal drugs in serum by ultra-high pressure liquid chromatography and diode array detection
MISTRETTA, Virginie ULg; DUBOIS, Nathalie ULg; DENOOZ, Raphael ULg et al

in Acta Clinica Belgica (2014), 69(1), 53-61

Azole antifungals are a group of fungistatic agents that can be administered orally or parenterally. The determination of the concentrations of these antifungals (miconazole, fluconazole, ketoconazole ... [more ▼]

Azole antifungals are a group of fungistatic agents that can be administered orally or parenterally. The determination of the concentrations of these antifungals (miconazole, fluconazole, ketoconazole, posaconazole, voriconazole, itraconazole, and its major active metabolite, hydroxy-itraconazole) in serum can be useful to adapt the doses to pharmacological ranges because of large variability in the absorption and metabolism of the drugs, multiple drug interactions, but also potential resistance or toxicity. A method was developed and validated for the simultaneous determination of these drugs in serum utilizing ultra-high pressure liquid chromatography and diode array detection (UHPLC-DAD). After a simple and rapid liquid– liquid extraction, the pre-treated sample was analysed on an UHPLC-DAD system (Waters CorporationH). The chromatographic separation was carried out on an Acquity BEH C18 column (Waters Corporation) with a gradient mode of mobile phase composed of acetonitrile and aqueous ammonium bicarbonate 10.0 M pH10. The flow rate was 0.4 ml/min and the injection volume was 5 ml. The identification wavelength varied according to the drug from 210 to 260 nm. The method was validated by the total error method approach by using an analytical validation software (eNnoval V3.0 ArlendaH). The seven azole antifungals were identified by retention time and specific UV spectra, over a 13-minute run time. All calibration curves showed good linearity (r2.0.99) in ranges considered clinically adequate. The assay was linear from 0.05 to 10 mg/l for voriconazole, posaconazole, itraconazole, hydroxy-itraconazole, and ketoconazole, from 0.3 to 10 mg/l for fluconazole, and from 0.1 to 10 mg/l for miconazole. The bias and imprecision values for intraand inter-assays were lower than 10% and than 15%, respectively. In conclusion, a simple, sensitive, and selective UHPLC-DAD method was developed and validated to determine seven azole antifungal drugs in human serum. This method is applicable to patient samples, and can be applied successfully to clinical applications and therapeutic drug monitoring. [less ▲]

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See detailRefractory hypercalcemia and ectopic calcitonin secretion in a malignant pancreatic neuroendocrine tumor: hypocalcemic effects on cinacalcet
VALDES SOCIN, Hernan Gonzalo ULg; rubio almanza, Matilde; LOLY, Jean-Philippe ULg et al

in Acta Clinica Belgica (2013), 68(6), 42

Introduction: Paraneoplastic hypercalcemia is a sign of poor prognosis, as it is particularly resistant to the usual hypocalcemic treatments. Observation: In 2009, a well differentiated pancreatic ... [more ▼]

Introduction: Paraneoplastic hypercalcemia is a sign of poor prognosis, as it is particularly resistant to the usual hypocalcemic treatments. Observation: In 2009, a well differentiated pancreatic neuroendocrine tumor (Ki-67= 2%) is diagnosed in a 52-year-old diabetic man. The tumor is revealed with a splenic and hepatic carcinomatosis. Plasmatic calcium was: 3.54 mmol/L (2.15 - 2.6). Biology showed hypophosphatemia, PTH < 4 ng/ml, high 1-25 OH VitD, calcitonin: 1016 ng/ml (< 12 ng/ml). He had hypercalciuria and hypophosphaturia. He received for two years several cycles of Streptozotocin-ADRIAMYCIN and FOLFOX, with partial control of the tumor mass and calcium levels. In 2012, calcitonin levels are 29 ng/ml whereas calcemia is 3.17 mmol/L. Hypercalcemia is refractory to hyperhydration, diuretics, corticosteroids, and bisphosphonates therapy. Cinacalcet (Mimpara) is prescribed up to 120 mg/day (PO). Calcemia decreases gradually from 3 to 2.87 and then 2.76 mmol/L. PTH and calcitonin-the tumor mass remain unchanged. After two months of Cinacalcet treatment, Sunitinib (Sutent) 37.5 mg per day was added. During the third month, calcium levels dropped to 2.09 mmol/L and PTH raised to 78 pg/ml, requiring discontinuation of Mimpara. Calcitonin normalized, with a further improvement over pancreatic and metastatic lesions. Conclusion: Cinacalcet is a Calcium Sensing Receptor oral agonist. Cinacalcet hypocalcemic effects have not been previously documented in pancreatic paraneoplastic hypercalcemia. In our patient, Cinacalcet has significantly improved cancer prognosis: this drug could be a new alternative in paraneoplastic hypercalcemia. [less ▲]

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See detailPersistent low levels of serum hCG: please do not miss phantom hCG! (pseudohypergonadotropinemia syndrome)
VALDES SOCIN, Hernan Gonzalo ULg; SYRIOS, Petros ULg; GADISSEUR, Romy ULg et al

in Acta Clinica Belgica (2013), 68(6), 465

Introduction: Beyond pregnancy, persistent low levels of hCG may be associated with various benign and malignant conditions, i.e. quiescent gestational trophoblastic disease (QTD), raised pituitary hCG or ... [more ▼]

Introduction: Beyond pregnancy, persistent low levels of hCG may be associated with various benign and malignant conditions, i.e. quiescent gestational trophoblastic disease (QTD), raised pituitary hCG or false positive elevation caused by circulating heterophilic antibodies. This situation requires a clinico-biological approach in order to avoid misunderstandings that could lead to inappropriate diagnostic or therapeutic attitudes. Observation: A 23 years old woman (GOPO status) consulted his gynaecologist because of persistent abdominal pain. She was diagnosed of having trophoblastic disease on the basis of persistently positive human chorionic gonadotropin (hCG) test (Roche Modular) results, in the absence of pregnancy. Persistent low levels of hCG (around 10 U/L) were detected in her plasma. The patient underwent a trial with methotrexate chemotherapy. Abdominal pain was unrelieved whereas plasma hCG was 8.9 U/L. A serology test for Chlamydia indicated persistent infection and a course of antibiotic treatment was underwent without any relief. A laparoscopic exploration ruled out any trophoblastic residue or pelvic adherences. The patient was referred to the Endocrine Unit for further pituitary and hormonal investigations. Plasma and urine samples were sent to Biology Service to exclude a false hCG positive value. While low levels of hCG were detected in serum by assay, no significant hCG was detected in the urine (0,1 U/L). When serum was treated with HBT tube for the detection of heterophilic antibodies, hCG levels were 0.98 U/L. After mouse serum treatment, hCG was not further detected in our patient, indicating the presence of phantom hCG due to the presence of human anti mouse heterophilic antibodies. Conclusions: Textbooks on obstetrics and gynecology emphasize the importance of plasma hCG testing in patients with trophoblastic diseases. The ability of laboratory measurements to guide the clinician appropriately in every circumstance is limited. Caution should be exercised when clinical findings and laboratory results are discordant. Current protocols for the diagnosis and treatment of trophoblastic disease should include a compulsory test for hCG in urine and a test for heterophilic antibodies when appropriate. In this case report, we demonstrated that phantom hCG, was caused by heterogenous human anti mouse antibodies. [less ▲]

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See detailInvestigation olfactive de la mort
Focant, Jean-François ULg; Stefanuto, Pierre-Hugues ULg; Brasseur, Catherine ULg et al

in Acta Clinica Belgica (2013, October), 68-6

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See detailQuantitative determination of non persistent endocrine disruptors in human urine
Dewalque, Lucas ULg; PIRARD, Catherine ULg; DUBOIS, Nathalie ULg et al

in Acta Clinica Belgica (2013), 68(6),

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See detailEvaluation de l'exposition professionnelle aux cytostatiques des travailleurs de deux services du CHU de Liège
Rusu, Dorina; DUBOIS, Nathalie ULg; Surleraux, Cécile et al

in Acta Clinica Belgica (2013), 68(6), 472

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See detailProspective study of an advanced nurse triage for a target pathology at the admission in the emergency department
JOBE, Jérôme ULg; VANDERCLEYEN, C; Ghuysen, Alexandre ULg et al

in Acta Clinica Belgica (2013), 68(6), 2

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See detailValidation of analytical method for the determination in serum of psychotropic drugs commonly prescribed in Rwanda by HPLC-DAD
Hahirwa, Innocent; Charlier, Corinne ULg; DENOOZ, Raphael ULg et al

in Acta Clinica Belgica (2013), 68(6), 479

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See detailBlood lead, urinary lead, urinary δ-aminolevulinic acid and urinary porphyrins levels among people living in kinshasa, D.R. Congo : a pilot biomonitoring study
Mputu Malolo, Corneille-Liévin; Ndelo di Phanzu, Josaphat; Marini Djang'Eing'A, Roland ULg et al

in Acta Clinica Belgica (2013), 68(6), 475

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See detailApplication de la résonance magnétique nucléaire (RMN) en toxicologie judiciaire
Denooz, Raphaël ULg; Frederich, Michel ULg; Charlier, Corinne ULg et al

in Acta Clinica Belgica (2013), 68(6), 470

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See detailUnexplained cardiac failure leading to the identification of a Belgian family affected by hereditary amyloidosis.
DE PASQUAL, Aurelie ULg; BIESSAUX, Yves ULg; Blettard, Noelle et al

in Acta Clinica Belgica (2013), 68(4), 303-305

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See detailAcute cholecystitis with Listeria monocytogenes
DESCY, Julie ULg; De Mol, Patrick ULg; HAYETTE, Marie-Pierre ULg et al

in Acta Clinica Belgica (2012), 67(4), 295-297

Listeriosis, an opportunistic food-borne disease caused by Listeria monocytogenes, is infrequent and occurs preferentially in patients at the extremes of age, during pregnancy or in immunocompromised ... [more ▼]

Listeriosis, an opportunistic food-borne disease caused by Listeria monocytogenes, is infrequent and occurs preferentially in patients at the extremes of age, during pregnancy or in immunocompromised hosts. Most common manifestations are maternofoetal and neonatal infections, severe invasive presentations such as bacteraemia with or without central nervous system symptoms occuring preferentially in immunosuppressed patients and self-limited gastro-enteritis affecting healthy individuals. Exceptionally, focal infections such as cholecystitis are described. We report here a case of acute cholecystitis caused by Listeria monocytogenes in an 82-year-old woman. Thanks to a successful treatment: cholecystectomy and antimicrobial therapy (amoxicillin plus clavulanic acid), the patient soon recovered. This case-report provides an opportunity to review the current literature concerning the association of Listeria monocytogenes and cholecystitis. [less ▲]

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See detailThe appearance of the thymus and the integrated evolution of adaptive immune and neuroendocrine systems
Geenen, Vincent ULg

in Acta Clinica Belgica (2012), 67

The immune system may be considered as a sensory organ able to respond to different kinds of danger signals that are not detected by nervous cells. The immune response is not autonomous but also regulated ... [more ▼]

The immune system may be considered as a sensory organ able to respond to different kinds of danger signals that are not detected by nervous cells. The immune response is not autonomous but also regulated by central and peripheral nervous system, as well as by neuropeptides, vitamin D and neuroendocrine axes such as the corticotrope, somatotrope, thyrotrope and gonadotrope axes. During evolution, the thymus emerged concomitantly with recombinase-dependent adaptive immunity as an ‘immune brain’ or a ‘master class’ highly specialized in the orchestration of central immunological self-tolerance. This was an absolute requirement for survival of species because of the high risk of autotoxicity inherent to the stochastic generation of extreme diversity characterizing this novel adaptive type of immune defenses against non-self. The thymus now appears to be an obligatory intersection for the integrated evolution of the major systems of cell-to-cell signaling, the nervous, endocrine and immune systems. The presentation of many self-peptides by thymic major histocompatibility complex (MHC) proteins is controlled by the autoimmune regulator (AIRE) gene/protein and is responsible for the clonal deletion of self-reactive T cells. In the same time, by still unexplained mechanisms, MHC presentation of the same self-peptides in the thymus promotes the generation of self-specific FOXP3+ CD4+CD25+ natural regulatory T cells (nTreg) that are able to inhibit in periphery self-reactive CD4+ and CD8+ T cells having escaped the thymus censorship. Moreover, a thymus dysfunction is more and more established as the primary event driving the development of organ-specific autoimmunity, which is the tribute paid, mainly by mankind, for the preservation of self against non-self. Our novel knowledge about thymus physiology and physiopathology already serves as the basis for the development of various innovative and efficient immunomodulating strategies in pharmacology. [less ▲]

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See detailA national cohort of HIV-infected patients in Belgium: design and main characteristics.
Van Beckhoven, D.; Buve, A.; Ruelle, J. et al

in Acta Clinica Belgica (2012), 67(5), 333-7

In Belgium, individual laboratory and treatment data of all HIV-infected patients seen in the 9 AIDS Reference Centres and 7 AIDS Reference Laboratories are collected prospectively since 2006. We present ... [more ▼]

In Belgium, individual laboratory and treatment data of all HIV-infected patients seen in the 9 AIDS Reference Centres and 7 AIDS Reference Laboratories are collected prospectively since 2006. We present here an analysis of patients recorded in the cohort database between 1st of January 2006 and 31st of December 2008. During that period, 11982 patients were under medical follow-up in Belgium. Sixty-one percent of the patients were male and the median age was 39.8 at the time of first recorded viral load. Among the patients whose nationality or probable mode of transmission was recorded, nearly half (48.0%) were Belgian and 38.3% originated from Sub-Saharan Africa; heterosexual contacts were reported in the majority of cases (56.0%) followed by homosexual contacts (35.3%). A total of 145 deaths were reported. Around three quarters of the patients were on ART. The median CD4 cell count rose from 470 cells/mm3 in 2006 to 501 cells/mm3 in 2008. This cohort enabled us to obtain comprehensive information on the numbers and characteristics of HIV-infected patients currently being followed up in Belgium, and on trends in antiretroviral therapy and biological results. This will serve for planning purposes, evaluation of access to care and as a source of information for further studies. [less ▲]

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