Search PubMed⌕ Search

Biomedical subjects

A Laffont

Publications and source records attributed to A Laffont.

9 recordsLinked to original sources

Diurnal changes in the pharmacokinetic behavior of amikacin.

This retrospective study evaluated possible differences in the pharmacokinetic behavior of amikacin between the morning (AM) and evening (PM). Of 634 patients receiving amikacin therapy, 17 received a dose every 12 hours (an i.v. infusion at 8:00 AM and 8:00 PM) with amikacin serum levels obtained after both the AM and PM infusions. Pharmacokinetic parameter values were estimated by the nonparametric EM algorithm (USC*PACK clinical software) for a one-compartment model. All patient data were analyzed in three ways. The parameter values were estimated by fitting the model first only to the serum levels drawn following the AM dose; second, only to the data following the PM dose; and third, to all serum levels (AM + PM). Parameter values found were (mean, median, SD respectively): AM: Kel = 0.181114 h(-1), 0.224460 h(-1), 0.058820 h(-1); Vol = 23.657507 L; 23.376231 L; 1.353253 L; Cl = 4.326720 L x h(-1), 5.303726 L x h(-1), 1.447731 L x h(-1); PM: Kel = 0.110151 h(-1); 0.121295 h(-1); 0.016860 h(-1); Vol = 28.948043 L; 24.091703 L; 9.266628 L; Cl = 3.081761 L x h(-1), 2.810615 L x h(-1); 0.705874 L x h(-1); AM + PM: Kel = 0.165321 h(-1); 0.131796 h(-1); 0.075425 h(-1); Vol = 25.479043 L; 26.187970 L; 5.367054 L. These findings are in agreement with the known diurnal rhythm of glomerular filtration rate. Because pharmacokinetic parameter values are most often estimated using AM data, this may lead to an overevaluation of these values compared with PM or to values for the entire day. The resulting drug regimens may therefore be overestimated regarding the elimination rate constant and underestimated regarding the volume of distribution.

Adult↗

[Cardiovascular impact of end-stage renal insufficiency in children undergoing hemodialysis].

Cardiac hypertrophy and arterial dysfunction have been described in end-stage renal disease (ESDR) in adults. The incremental elastic modulus (Einc), is a marker of vascular wall material stiffness and an independant predictor of cardiovascular mortality in adults with ESRD on hemodialysis. The relationship between arterial changes and the heart is unknown in the children with ESRD in the same conditions. Using a high-resolution vascular ultrasound and a computerized system of measurement (Iotec), we assessed noninvasively 10 ESRD patients (mean +/- SD, age, 11.5 +/- 4 years; blood pressure [BP], 120 +/- 10/63 +/- 4 mmHg) and 10 age-, sex-, and BP-matched controls (mean +/- SD, age, 11 +/- 4 years; BP, 114 +/- 8/58 +/- 8 mmHg). The systolic and diastolic diameter of the common carotid artery (CCA), the thickness of the wall (intima-media thickness, IMT), the cross sectional compliance (CSC), the cross sectional distensibility (CSD) and the (Einc) were determined. CSC and CSD were evaluated at the same level of pressure. The CCA pressure waveform was obtained by applanation tonometry to assess the reflected wave by the augmentation index (AI). Further the left ventricular mass index was assessed. The flow mediated dilation (FMD) (endothelium-dependent function) and the vasodilation induced by glyceryl-trinitrate (GTNMD) (GTN, an endothelium-independent dilator) were evaluated at the brachial artery site. Compared to control subjects, ESRD patients have mechanical artery dysfunction with lower CSC and CSD (0.11 +/- 0.04 vs 0.18 +/- 0.05 mm2.mmHg-1; p < 0.01; 0.43 +/- 0.10 vs 0.82 +/- 0.20 mmHg-1.10(-2); p < 0.001) and higher Einc (2.60 +/- 1.00 vs 1.40 +/- 0.30 mmHg.10(3); p < 0.001). Furthermore an earlier return of the reflected pulse wave (AI -0.24 +/- 0.08 vs -0.58 +/- 0.06; p < 0.005) is correlated to LV mass index (r = 0.55, P < 0.01) that is significantly increased (134 +/- 63 vs 69 +/- 25 g/m2; p < 0.005). These patients have an impaired FMD (4 +/- 2 vs 7 +/- 1%; p = 0.02) with a normal GTNMD. This study shows that early arterial dysfunction can occur in children with ESRD.

Adult↗

[Biological diagnosis of immediate drug allergy. Comparative study of histamine liberation tests and CD63 expression by flow cytometry (preliminary results)].

The diagnosis of drug allergy is mainly based upon a detailed clinical history, positive skin tests (ST) and detection of specific IgE. In case of discrepant results, in vitro investigations to identify the responsible drug are needed. The histamine release test (HR) is usually performed. Nevertheless, its clinical benefit remains controversial. Flow cytometric methods (FCM) for the study of allergen induced basophil activation have been recently described. We assessed their usefulness in the diagnosis of drug allergy in comparison to HR results. Eighteen patients were included and 24 drugs (mainly antibiotics and muscle relaxant drugs) were tested. On the basis of clinical signs, 15 patients were classified as allergic (18 drugs). Sensitivity of biological investigations were found as follows: 71% (ST), 71% (FCM) and 24% (HR). This suggests performing FCM rather than HR. In addition, HR is more costly in terms of both reagents and laboratory technician time. Thus, CD63 detection by FCM seems to be a more reliable method in the clinical immunology laboratory. Additional data are needed to validate these preliminary results (sensitivity and specificity, especially in atopic patients) and to assess the interest of the method to investigate drug allergy due to other types of molecules.

Antigens, CD↗

Determination of ceftazidime in plasma using high-performance liquid chromatography and electrochemical detection. Application for individualizing dosage regimens in elderly patients.

This study describes a sensitive HPLC-electrochemical detection method for the analysis of ceftazidime, a third-generation cephalosporin, in human plasma. The extraction procedure involved protein precipitation with 30% trichloroacetic acid. The separation was achieved on a reversed-phase column (250X4.6 mm I.D., 5 microm) packed with C18 Kromasil with isocratic elution and a mobile phase consisting of acetonitrile-25 mM KH2PO4-Na2HPO4 buffer, pH 7.4 (10:90, v/v). The proposed analytical method is selective, reproducible and reliable. The assay has a precision of 0.2-15.1% (C.V.) in the range of 5-200 microg mil(-1). (corresponding to 0.5 to 20 ng of ceftazidime injected onto the column), and is optimised for assaying 50 microl of plasma. The extraction recovery from plasma was approximately 100%. The method was highly specific for ceftazidime and there was no interference from either commonly administered drugs or endogenous compounds. This assay was used to measure ceftazidime in elderly patients for therapeutic drug monitoring.

Aged↗

[Individual variability of pharmacokinetic parameters of amikacin in the elderly: retrospective studies].

UNLABELLED: In previous works, we have shown: i) good parameter predictive performances of the USC*PACK Clinical Programs for amikacin therapy in the elderly, ii) no significant difference generally detected between estimated parameter values at days 7 and 14 after the beginning of therapy, iii) assurance of neither accumulation nor toxicity during therapy up to 14 days or more, in our conditions. The objectives of this study were to explore which elements best explained differences found in the pharmacokinetic parameters (PK) of the elderly patients, who had received several courses of amikacin therapy. METHODS: patients' pharmacokinetic data and their medical records were retrospectively analyzed. Only patients who received amikacin therapy with at least a 2-month washout between their courses were studied. Two parameterizations of the 1-compartment PK model were used: one without covariates: Kel-Vol, where Kel = elimination rate constant and Vol = distribution volume, and another including covariates: Ks-Vs, with: Kel = Ks. CCr + Ki, where: Ks = renal fraction of Kel, Ki - non renal elimination, CCr = estimated creatinine clearance, and Vs = Vol/W, where Vs = distribution volume per kg and W = weight. RESULTS: 14 patients, 3 men and 11 women, fulfilled the criteria (4 of them satisfied the condition with 3 courses). They were 66 to 89 years old, their mean weight was 53.86 +/- 11.03 kg (46-71.5), their CCr averaged: 55.45 +/- 17.16 mL/min (14.84-96.27). CONCLUSION: Among patients exhibiting changes (67%) in PK parameters between different courses of therapy, 42% could have the variability related to covariate (W, CCr) changes; in the others 58% the residual variability could be explained by different factors: severity of infection, immune system deficiency and/or particularly parenteral nutrition. Based on these result, we suggest including septic choc and parenteral nutrition as covariates during amikacin adaptive control.

Age Factors↗

[The hospital course of thrombolyzed myocardial infarction: role of bypass and angioplasty].

The frequency of indications for revascularization (bypass and angioplasty) after intravenous thrombolysis in myocardial infarction (MI) varies from 3.3% (Gissi) to 60% (Tami). Initial progress in 30 patients hospitalized consecutively for MI treated by thrombolysis (group A) was compared with that of 30 MI patients treated conventionally (group B) over the same period. There were no between group differences in age, sex, infarction history, bypass history, topography of infarction or extent of coronary lesions. Group A was characterized by a larger ejection fraction (51.7 +/- 9.2% vs 44.9 +/- 10%; p less than 0.05), a higher frequency of ischemic recidivism (33% vs 10%; p less than 0.05), and more frequent indications for secondary revascularization (50% vs 20%; p less than 0.02).

Adult↗

[Synthesis].

Explore the source record for details and available documents.

Disease↗