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Infliximab (IFX) is a chimeric monoclonal antibody which has proven its efficacy in the treatment of inflammatory diseases. However, its efficacy can be limited by the development of anti-IFX antibodies (ATI) resulting in a therapeutic failure of IFX. ATI plasmatic monitoring is then indicated to optimize IFX treatment. The aim of this study was to validate an ELISA (enzyme linked immuno sorbent assay) method of ATI plasmatic monitoring. Methods Assessment of performance was based on the study of correlation and concordance (Bland Altman method) of the absorbances measured by the two readers. ELISA kit validation was made by calculating the accuracy and the exactitude. Results We collected 23 samples. Their mean age was 46 years and sex ratio M/W was 0.92. In nine cases, plasmatic AIT were positive and in 14 cases, they were not detected. Correlation between the two readers showed a correlation coefficient r2 of 99.95%. Concordance limits of the confidence interval 95% were [-112.768%-41.425%] with a bias of -35.671%. Repeatability and reproductibility were checked by a positive control and coefficients of variation were respectively of 5.574% and 14.184%. Limits of detection and quantification were respectively of 0.046 and 0.086. The positive predictive value was 0.5 and the negative predictive value was 1. The sensitivity was 100% and the specificity was 83%. Conclusion The assessment of the performance of the tested microplate reader and the validation of the tested ELISA kit showed good results allowing ATI routine measurement to optimize therapeutic management of patients treated by IFX.

To evaluate the modalities of administration of antiepileptic drugs (AED) with nasogastric tube (NGT) by nurses and to draw up recommendations.Our study consisted on investigating the modalities of administration of AED's with NGT by nurses during four months. We prepared 10 questions including demographic information. Participation was voluntary and anonymous. The questionnaire was distributed in seven intensive care departments after authorization of each head of the department. Thus, 45 nurses were included.Nurses sex ratio was 1.5 and mean age was 31 years (25 to 37 years). Among the nurses, 60% mentioned that the NGT were silicone made and 4% that they were PVC made. The mean duration before replacing the NGT was thought to be 5±3 days. Among the nurses, 91% affirmed to clear the NGT after each use. All the nurses had agreed that the solid form is the most commonly used pharmaceutical form in the NGT. AED were associated with the enteral feeding solution in 56%. The AED should be crushed before administration for 98% of the nurses even in case of polymedication. Among them, 62% recommended to crush all of the associated drugs together. Before introducing the AED into the NGT, 93% of the nurses reported mixing with tap water. We have noticed that 62% of nurses felt the need to improve their knowledge AED administration with NGT.To optimize AED therapy, modalities of administration by NGT in epileptic comatose patients should be enhanced.

Lamotrigine is an effective anticonvulsant drug used in the treatment of epilepsy. It has a narrow therapeutic range, a large inter and intra-individual pharmacokinetic variability and some concentration-dependent side effects.The aim of this study was to develop and validate a new method for lamotrigine quantitation in plasma using HPLC with UV/visible detection.A rapid HPLC-UV method was developed for the determination of lamotrigine in plasma. All solvents used were HPLC grade.After liquid-liquid extraction, chromatographic separation was achieved using an RP 18 (250 mm) column. The mobile phase was composed of acetonitrile and 0.1 M potassium dihyrogenophosphate (25/75) (v/v). Barbital sodium was used as internal standard. This technique was linear over the 2 μg/mL to 50 μg/mL range (r= 0.99). Detection and quantification limits were 0.07 μg/mL and 0.21 μg/mL, respectively. Within-day coefficient of variation (13.37 to 16 %) and day-to-day coefficients of variation (15.68 to 16.63 %) at three different concentrations. Under these conditions, each analysis required no longer than 10 min. We finally evaluated the plasma concentrations of lamotrigine in Tunisian patients treated with this drug.The results found are similar to those previously described and the developed method is repeatable and reproducible. It can be used for clinical applications.

Ciclosporine (CsA) is an immunosuppressant drug used in bone marrow transplantation in order to extend allograft survival. Despite its efficiency, CsA can expose to therapeutic failure or to toxicity because of underdosing or overdosage. So, many techniques of monitoring CsA in blood were used, the referance one is the chromatographic technique then, the automated techniques: fluorescence polarization immunoassay (FPIA) and chimiluminescent microparticle immunoassay (CMIA). In this study, we aimed to compare the results of CsA concentrations measured by the two automised techniques. Statistical studies showed that the two techniques were repeatable and reproductible. Results obtained by FPIA were slightly higher than those obtained by CMIA but without a significative difference. In conclusion, FPIA technique could be used to measure CsA blood concentration in replacement of CMIA in case of technical problems.

Valproic acid (VA) is a widely used antiepileptic drug. Because of its pharmacokinetic variability and the influence of intrinsic and extrinsic factors such as the treatment compliance, VA therapeutic drug monitoring (TDM) is recommended in children. The aim of this study is to evaluate the effect of treatment compliance and the economic level on VA tough plasmatic concentration (TPC) and epileptic rhythm in children.A one-year prospective study (August 2008-August 2009) concerning children (age≤5 years) regularly treated by VA who had a VA TDM. So, 276 plasmatic samples from 238 children were collected. The children were divided in two groups as following: the group 1 (G1) presenting a good compliance and a reliable questioning and the group 2 (G2) presenting a bad compliance and a non reliable questioning. We evaluated the interindividual variability by correlating the TPC to the dose. Then, we divided the hole group in function of their economic levels (low-medium-high).Sex ratio male/female was 1.3. Median age was 5 years+/-3,9. The mean TPC was 62 µg/mL [0.12-131 µg/mL]. VA TPC were in the therapeutic range (TR) in 62%. Adverse drug reactions were noted in 4.2% of the children. G1 represented 70% of the children and G2, 30%. The TPC were in the TR in 67% of G1 and 51% of G2 (p=0.02). There was a significant difference between the TPC in G1 and G2 (p=0.02).There was no significative difference in the TPC in function of the economic levels. There was no correlation between TPC and the administered doses. The epileptic seizures were more spaced in children with therapeutic TPC than those with TPC in the TR (p=0.002) and in G1 than in G2 (p=0.03).Compliance should be appropriate in order to optimize the TDM rule. A good compliance and a therapeutic TPC allow a better control of epileptic seizures.

Methotrexate (MTX) is a folic acid antagonist used at high-dose intravenously on 24 hours (24h) in the treatment of the acute lymphoblastic leukemia (ALL). To prevent potential toxicity, MTX is usually administered following the application of preventive measures. We report a case of an accidental shortening time for high dose MTX infusion and a literature review of accidental intoxications by the MTX. This case illustrates the importance of the respect of MTX high dose infusion time and the major role played by the therapeutic drug monitoring.

The objective of our work is to search if there is a relation between azathioprine's metabolites (6-thioguanines nucleotides and 6-methyl mercaptopurines) and clinical efficacy and adverse effects of azathioprine in inflammatory bowel disease population.We included patients with Crohn's disease or ulcerative colitis (UC) treated by azathioprine for a duration more than 1year. Each patient had a dosage of azathioprine metabolites.We included 43 Crohn's disease patients and 7 UC. Azathioprine was indicated for steroid dependancy in 23 cases, to prevent post-operative recurrence in 10 cases, to maintain clinical remission obtained by medical treatment in 17 patients. A clinical response to azathioprine (obtention of remission, absence of recurrence during the follow up) was observed in 34 patients.Our work confirms the relation between the doses of azathioprine metabolites and the myelotoxicity due to this molecule.

The objective of our work is to search if there is a relation between azathioprine's metabolites (6-thioguanines nucleotides and 6-methyl mercaptopurines) and clinical efficacy and adverse effects of azathioprine in inflammatory bowel disease population.We included patients with Crohn's disease or ulcerative colitis (UC) treated by azathioprine for a duration more than 1 year. Each patient had a dosage of azathioprine metabolites.We included 43 Crohn's disease patients and 7 UC. Azathioprine was indicated for steroid dependancy in 23 cases, to prevent post-operative recurrence in 10 cases, to maintain clinical remission obtained by medical treatment in 17 patients. A clinical response to azathioprine (obtention of remission, absence of recurrence during the follow up) was observed in 34 patients.Our work confirms the relation between the doses of azathioprine metabolites and the myelotoxicity due to this molecule.

Frequency of colitis induced by drugs is often under estimated. Antibiotics and nonsteroidal anti-inflammatory drugs (NSAIDS) are usually incriminated. In this study, we classified colitis according to the main responsible drug with a focus on clinical symptomatology, physiopathology, evolution, and complications. We describe colitis due to antibiotics, NSAIDS, laxatives, vasoconstrictive agents, oestroprogestatives, chemotherapy and drugs induced microscopic colitis. The last one represents a particular case; it can be idiopathic, infectious or drugs induced. Its physiopathology is not well known and its diagnosis is based only on histologic criterion. Drug responsibility is easy to determine only for pseudomembranous colitis. In the other cases, chronology is very variable and the clinical, endoscopic and histological elements are rarely specific. Because of the large number of drugs that may induce colitis, it is necessary to search for potentially responsible drugs, especially if there is no obvious cause of the colitis.

Postmenopausal osteoporosis is especially female pathology, whose incidence increases with age.The purposes of this study are to evaluate the level of bone turnover by the determination of markers of bone formation (PAL, BAP) and marker of bone resorption (CTX) in the osteoporotic women, to study the correlations between bone biochemical markers, clinical parameters and radiological measurements and to assess the interest of biochemical markers therapeutic monitoring after 6 months of antiresorptive treatment.The authors report a prospective study of 134 osteoporotic women classified in two groups according to the presence of osteoporotic fracture. Patients of the first group G1 (n=102) with fractures, were treated by the bisphosphonates (risedronate), whereas the ones of the second group G2 (n=32) without fractures, were submited to calcic supplementation and vitamin D.The analyses showed that the femoral and lumbar BMD were statistically lower in the presence of osteoporotic fractures. However, the values of CTX were statistically higher in the patients of G1 group compared to those of the G2 group (0,708 +/- 0,332 ng/ml versus 0,514 +/- 0,225 ng/ml). The CTX were statistically correlated with the femoral and lumbar BMD (r = -0,21, p0,05 and r= -0,348, p0,001). The hypovitminosis were observed in 50,98% (52/102) of women with ostéoporotic fractures, whereas it was only 25% (8/32) in women without fractures. After 6 months of treatment by the bisphosphonates, the PAL, the BAP and the CTX have decreased with an average of, respectively, 19%, 46,5% and 62,9%. These variations were significantly more important in G1 group.The biochemical markers of bone turnover, in particular those of the resorption (CTX), can predict the postmenopausal woman's bone loss evaluated by BMD, the risk of fractures and the efficiency of the bone treatments.

Paracetamol is an extensively used analgesic and antipyretic. Allergy to this drug is occasionally reported and is usually moderate.We led a retrospective study of 119 cases of allergic reactions to paracetamol notified to the Tunisian centre of pharmacovigilance, between September 1990 and September 2000. These cases were validated according to the method of imputability of Bégaud et al.Our population comprised 64 women and 55 men, aged 1 month to 70 years. Antecedents of allergy or atopy were found in many cases, including 10 cases of allergy to paracetamol and 6 to salicylates. Paracetamol was self-administered in 50% of cases and taken with other drugs in 68% of cases. The type of lesions varied, the most frequent being urticaria (34.4%), macular and pustular eruption (30.2%) and fixed drug eruption (12.6%). Some reactions were serious, such as Lyell syndrome or anaphylactic shock. Resolution was favourable in all cases and paracetamol was definitively contraindicated for patients with scores of high or mild imputability.Allergy to paracetamol seems to be rare but not exceptional. Several risk factors seem to be important in triggering this side effect, particularly antecedents of allergy to this drug or to aspirin.