High-performance liquid chromatographic separation of fluoroquinolone enantiomers: a review.

Fluoroquinolones are antibacterial agents widely used clinically. In recent years, there has been an important development of new derivatives, and more than 7000 analogues have been described today. Different fluoroquinolones (FQ) have one or two chiral centers in their chemical structure and are available as racemates, diastereoisomers, or pure enantiomers. The clinical and pharmaceutical uses of these compounds need effective analytical procedures for quality control and pharmacodynamic and pharmacokinetic studies. This review article focuses on the high-performance liquid chromatographic separation of fluoroquinolone stereoisomers by the use of derivatization methods and ligand exchange (LE) or chiral liquid chromatography.

Uptake of quinolones by in-vitro human monocyte derived macrophages.

We have developed an in-vitro model of monocyte-derived macrophage (MDMphi) to compare fluoroquinolone uptake in monocytes and derived macrophages. Monocyte-derived macrophages were obtained in-vitro by cultivating freshly isolated monocytes for seven days in RPMI 1640 medium, containing foetal calf serum and Rhu granulocyte-macrophage colony stimulating factor. Final suspensions contained 95% viable cells and 63% macrophages. Intramacrophagic accumulation of ciprofloxacin, ofloxacin or sparfloxacin was measured at equilibrium after 30-min incubation in the presence of 16-18 microg mL(-1) antibiotic. The results revealed low intracellular accumulation of ofloxacin in MDMphi (intracellular/extracellular ratio: IC/EC = 1.7). Ciprofloxacin and sparfloxacin uptake was significantly higher. The IC/EC ratios were only slightly increased in macrophages when compared with monocytes under the same experimental conditions. These results suggest that maturation of monocyte to macrophage has only a limited effect on basal quinolone uptake. Monocytic maturation cannot explain the important differences between fluoroquinolone accumulation in monocytes and tissue macrophages. Cell activation may be a greater determinant.

[Audit on pelvimetry at a polyvalent radiology department]. / Audit sur les pelvimétries d'un service de radiologie polyvalente.

PURPOSE: Study of the dose absorbed by the fetus during CT pelvimetry. MATERIAL AND METHODS: Twenty consecutive pelvimetries on pregnant women showed the mean fetal location in regard of the maternal pelvic skeleton (retrospective study). Then, thermoluminescent radiation detectors were put in the antropomorph phantom slices, in housing correspondent to the fetal's volume. The location of this volume has been determined by the first study. Two different CT units were tested. RESULTS: In case of cephalic presentation, the maximum fetal dose was 3 mGy. In case of pelvic presentation, because of an additional frontal topogram, the dose reached 3,3 to 3,6 mGy. CONCLUSION: We recommend: 1) reduction of parameters (120kV and 100mAs) for "normal" women; using other parameters for larger women; interval follow-up to evaluate results using these parameters; 2) tilting the bisciatic plane of section so to avoid direct exposure to the fetus; 3) limitation to 25 cm for the lateral scout; suppression of the routine frontal scout in case of pelvic presentation.

Determination of phosphonoformate (foscarnet) in calf and human serum by automated solid-phase extraction and high-performance liquid chromatography with amperometric detection.

An isocratic high-performance liquid chromatographic method with automated solid-phase extraction has been developed to determine foscarnet in calf and human serums. Extraction was performed with an anion exchanger, SAX, from which the analyte was eluted with a 50 mM potassium pyrophosphate buffer, pH 8.4. The mobile phase consisted of methanol-40 mM disodium hydrogenphosphate, pH 7.6 containing 0.25 mM tetrahexylammonium hydrogensulphate (25:75, v/v). The analyte was separated on a polyether ether ketone (PEEK) column 150x4.6 mm I.D. packed with Kromasil 100 C18, 5 microm. Amperometric detection allowed a quantification limit of 15 microM. The assay was linear from 15 to 240 microM. The recovery of foscarnet from calf serum ranged from 60.65+/-1.89% for 15 microM to 67.45+/-1.24% for 200 microM. The coefficient of variation was < or = 3.73% for intra-assay precision and < or =7.24% for inter-assay precision for calf serum concentrations ranged from 15 to 800 microM. For the same samples, the deviation from the nominal value ranged from -8.97% to +5.40% for same day accuracy and from -4.50% to +2.77% for day-to-day accuracy. Selectivity was satisfactory towards potential co-medications. Replacement of human serum by calf serum for calibration standards and quality control samples was validated. Automation brought more protection against biohazards and increase in productivity for routine monitoring and pharmacokinetic studies.

Uptake of fluoroquinolones in human monocytes isolated from peripheral blood.

The aim of this study was to develop a technique for separating monocytic cells in suspension from peripheral blood to measure the intracellular penetration of three fluoroquinolones (ofloxacin, ciprofloxacin and sparfloxacin). Mononucleated cells were isolated from the blood on a density gradient with lymphoprep and purified by a specific technique of adhesion and disadhesion on fibronectin. The monocytes were obtained in suspension with 76.8% purity and 97.9% viability. This was a convenient form for measurement of intracellular accumulation by use of the velocity-centrifugation technique. Intra-monocytic penetration of ciprofloxacin, ofloxacin and sparfloxacin was measured at equilibrium after 30-min incubation in the presence of 16 microg mL(-1) antibiotic. The results revealed low intra-monocytic accumulation of ciprofloxacin (intracellular-extracellular = 1.76) and ofloxacin (intracellular-extracellular = 1.42). The penetration of sparfloxacin was significantly higher (intracellular-extracellular = 2.4). This study confirms the important differences between human immunocompetent cells in terms of their ability to concentrate quinolones. It also underlines the importance of monocyte-macrophage cellular differentiation as a determinant of antibiotic penetration.

[Imaging of small renal tumors]. / Imagerie des petites tumeurs rénales.

The increased incidence of detection of small renal tumours, less than or equal to 3 cm in diameter, is related to the generalization and improvement of radiological techniques. Many asymptomatic renal tumours are discovered by ultrasonography and computed tomography. Medical imaging is now able to identify simple cysts (morphological characters, absence of blood supply), angiomyolipomas (demonstration of the fatty contingent) and other solid renal tumours (tumour enhancement on computed tomography). Plain, followed by postcontrast CT looking for contrast enhancement of the lesions is the examination of choice in this context. MRI with Gadolinium injection looking for neoplastic enhancement can be useful in doubtful cases. Medical imaging is able to reliably demonstrate the vascular nature of solid lesions, but cannot distinguish between renal cancer, oncocytoma or another benign solid tumour. Medical imaging allows precise preoperative mapping when partial nephrectomy is envisaged.

Demonstration of efficacy of combining corticosteroids and colchicine in two patients with idiopathic sclerosing mesenteritis.

Sclerosing mesenteritis is an uncommon condition of unknown etiology. It is likely to be the fibrous evolution of mesenteric panniculitis. It often has an indolent course but may be complicated by progressive bowel obstruction. The treatment of the symptomatic forms is not well established. The observations of two women (20 and 65 years old) with a relentless downhill course of biopsy-proved sclerosing mesenteritis are described. A treatment regimen with corticosteroid therapy (initially 1 mg/kg/day) and colchicine (1 mg/day) led, in both cases, to a rapid improvement. Abdominal computer tomography showed reduction in the tumor size. The combination of corticosteroids and colchicine is helpful in the management of symptomatic sclerosing mesenteritis. Follow-up with abdominal computed tomography is useful in evaluating the therapeutic impact.

Comparative uptake of sparfloxacin and ciprofloxacin into human THP 1 monocytic cells.

The uptake of sparfloxacin (CAS 11542-93-9) by human monocytes was studied by comparison with ciprofloxacin (CAS 86393-32-0). The human monocytic THP 1 cells were incubated with the antibiotics for 2 h. Entry of antimicrobials into the cells was determined by means of a velocity gradient centrifugation technique and HPLC assay. Antibiotic uptake was expressed as the ratio of the intracellular to the extracellular drug concentration (IC/EC). Quinolones enter readily in monocytic cells but sparfloxacin is taken up more rapidly than ciprofloxacin. At steady-state the IC/EC ratio of sparfloxacin (9.07) is higher than IC/EC of ciprofloxacin (4.29). Characterization of quinolone uptake suggests that these drugs penetrate throughout the THP 1 membrane by passive diffusion. However, the results of the present study indicate that additional mechanisms may contribute to intracellular accumulation of ciprofloxacin and sparfloxacin. Gemfibrozil, an inhibitor of organic anion transport, increases the accumulation of ciprofloxacin but does not modify IC/EC of sparfloxacin. It can be concluded that human monocyte-like cells have functional organic anion transporters and that this way of secretion is quinolone selective.

[Transplacental passage of epirubicin]. / Passage transplacentaire de l'épirubicine.

We studied the transplacental transfer of epirubicin, an anthracycline used for the treatment of different neoplastic disorders, in particular breast cancers, by in vitro perfusion of term human placenta. Placenta from women with uncomplicated pregnancy were collected immediately after vaginal delivery and put into 37 degrees C thermostated hood. Perfusion of foetal surface of the placenta by modified Earle's solution was started immediately after catheterisation at a flow rate of 6 ml/min and then so was the perfusion of the intervillous space at the rate of 12 ml/min. Samples were collected at different times after the initiation of the perfusion from arterial inflow and venous outflow respective of the maternal and foetal compartment. The transplacental transfer of epirubicin was investigated for two doses: 5 and 9 micrograms/ml. The mean transfer value of epirubicin is low (3.66 +/- 1.07%) for the two tested doses and is only slightly higher than doxorubicin transfer, which drug has provided rare accidents in the clinical reports. These results are in favour of a low placental toxicity of epirubicin. Clinical data have to be collected from pregnant women to confirm the low foetal toxicity of epirubicin.

Iohexol in patients undergoing urography: a comparison of polypropylene containers (Unique Soft Pack) and glass vials.

The purpose of the present phase IV multicentre trial was to evaluate general patient tolerance to Omnipaque 350 mgI/ml (iohexol) supplied in polypropylene containers compared to that of the same product supplied in routinely used glass vials, with emphasis on allergy-like adverse events. Polypropylene is a pure plastic material with practically no additives, and has been tested in vitro as a contrast medium packaging material for several years. Handling of these containers is easier and safer than handling of glass vials. Iohexol was administered to 1481 patients undergoing urography (741 patients in the glass vial group, 740 in the polypropylene container group), all of whom successfully participated in the trial. Six centres, representing four European countries, participated. Patients were randomized to receive iohexol from either polypropylene containers or traditional glass vials according to a double blind, parallel design. Pre-established inclusion and pre-admission exclusion criteria were followed, as well as routine procedures for preparation of the patients and conduct of the urography examinations at each hospital. Patient tolerance was assessed by recording all adverse events experienced over a period of up to 1 h after the procedure. Allergy-like events were defined as coughing, sneezing, nausea, vomiting, urticaria or itching. No adverse events were experienced by 56.5% of the patients in the glass vial group, nor by 58.0% of those in the polypropylene group. Discomfort (mainly a sensation of warmth) was reported by 39.4% and 38.6% of the patients, and adverse events other than discomfort by 7.4% and 5.9% of the patients, respectively. There seemed to be a correlation between the speed of injection and the frequency of discomfort (an increase with increasing speed), both of which varied a lot between centres. There was no significant difference in the incidence of allergy-like events between the two groups. Such reactions were seen in 2.0% of patients in the glass vial group and 1.9% of those in the polypropylene container group. There was no significant difference between the patients' tolerance to iohexol supplied in traditional glass vials or in polypropylene containers. Therefore, the new polypropylene container can be recommended as a container for Iohexol.

Liver metastases: safety and efficacy of detection with superparamagnetic iron oxide in MR imaging.

PURPOSE: To evaluate the clinical and biologic safety of superparamagnetic iron oxide (SPIO) as a contrast agent in magnetic resonance (MR) imaging and to assess its efficacy in the detection of liver metastases. MATERIALS AND METHODS: Twenty adults with liver metastases underwent MR imaging at 1.5 T before and 1 hour after infusion of SPIO. Four spin-echo (SE) sequences and one gradient-echo (GRE) sequence were used. RESULTS: There were no adverse reactions. Alterations in serum protein, serum iron, transferrin, and ferritin levels and transferrin saturation coefficient were statistically significant. The mean tumor-to-liver contrast-to-noise ratio (C/N) increased markedly with all sequences. The best postcontrast tumor-to-liver contrast was obtained with the GRE sequence (repetition time msec/echo time msec = 300/15). The mean number of apparent lesions detected after administration of SPIO increased by 12 with the proton-density-weighted SE sequences (800/30 and 2,500/30), four with the T2-weighted SE sequence (2,500/90), and seven with the GRE sequence (300/15). CONCLUSION: SPIO is safe, increases tumor-to-liver C/Ns with some sequences, and improves the detection of liver metastases.

Rectal malacoplakia in renal transplantation: MR features.

This report describes the CT and MRI features of rectal malacoplakia in a renal transplant recipient. The lesion appeared strongly hyperdense (105 HU) on unenhanced CT and demonstrated hypointense signal on T1- and T2-weighted MR imaging with slight homogeneous enhancement after gadolinium injection. These characteristics distinguish this lesion from other more common neoplastic, inflammatory rectal lesions that are typically isointense on T1-weighted imaging and enhance variably after gadolinium injection. Characteristic intracytoplasmic siderocalcific spherules in malacoplakia can produce suggestive features on unenhanced CT and MRI.

[MRI: overview, technique, interpretation]. / I.R.M.: généralités, technique, interprétation.

The purpose of this paper is to describe the general principle of MRI, emphasising the practical conduct of the examination which consists of three main phases. The authors define the concepts of relaxation time and T1 and T2, essential parameters for the understanding of MRI. They simply explain how to recognise a predominance of T1- or T2-weighting on MRI images. They review the principal artefacts which must be recognised in order to avoid erroneous interpretation of the images. Lastly, they define the value of MRI in clinical urology, renal pathology, especially neoplastic, and prostatic and bladder disease.

[Pelvic lymph node groups in computed tomography. Topographic atlas]. / Groupes ganglionnaires pelviens en TDM. Atlas topographique.

This atlas was prepared to facilitate the diagnosis of lymph mode enlargement in the pelvic region and to improve topographic diagnosis. Fifty computed tomographies were performed after lymphography using centimetric pelvic slices in order to select eight levels for reference. A statistical analysis was conducted to establish a diagram of the mean number of lymph nodes on the right and left side for each level. A table was established indicating the mean number and standard deviation for each group of nodes for the 8 different levels. In addition, a control slice (chosen among 50) accounts for the morphology of the iliac vessels, of the lymph nodes and psoas muscle most frequently encountered at each level. The distribution of the groups of nodes shows why interpretation can be difficult, particularly at vessel bifucations and confluents. Precise morphology based on effective opacification, especially in the pelvic area, is required for positive and especially topographic diagnosis. Finally, the description of the medial border of the psoas muscle and its close relations with certain groups of lymph nodes can cause some problems because of the similar densities. The atlas is of great help here.

[Placental penetration of cefpirome (HR 810): study of fetal concentrations after in vitro infusions of human placenta at term]. / Pénétration placentaire du cefpirome (HR 810): étude des concentrations foetales après perfusion in vitro de placenta humaine à terme.

Cefpirome (CPO) is a new parenteral cephalosporin with a wide antibacterial spectrum. In order to explore the possibility of using CPO in late pregnancy, we studied its placental transfer in vitro in a model of human placenta infusion. Mother-to-foetus in vitro transfer of CPO is high, similar to that of amoxicillin, with a placental clearance index of 0.20. A pharmacokinetic simulation based upon this result and data from literature suggests that CPO concentrations in foetal blood and amniotic fluid should be appropriate for the treatment of severe materno-foetal infections in late pregnancy. These preliminary results need to be confirmed by in vivo pharmacokinetic and clinical studies before recommending the use of CPO in late pregnancy.

[Irradiation of the fetus and the child in radiodiagnosis. Low doses]. / Irradiation du foetus et de l'enfant en radiodiagnostic. Doses faibles.

Controlling irradiation of the conceptus, the child and the adolescent due to radiodiagnosis techniques is of particular importance since these age groups are more sensitive to ionizing irradiation than adults. In addition the conceptus (embryo or foetus) often receives whole-body irradiation. Based on the data in the literature, it can only be demonstrated that, under normal diagnostic conditions, irradiation risks do exist. However, the aim of applying ethical standards based on the "ALARA" concept is to reduce the potential irradiation-related risk and to sustain a sufficiently high level of awareness of the potential danger in health careworkers.

Sensitive high-performance liquid chromatographic method for the determination of labetalol diastereoisomers in plasma samples without derivatization.

A direct high-performance liquid chromatographic assay for the determination of labetalol diastereoisomers in plasma without derivatization was developed. Baseline resolution of diastereoisomers was accomplished on a C18 bonded reversed-phase polymeric column with a basic (pH 11.5) mobile phase and isocratic elution. Sample treatment was optimized in order to achieve a complete extraction of labetalol diastereoisomers and to avoid racemization during extraction. Fluorimetric detection improved the selectivity and afforded a detection limit of 3 ng/ml for each diastereoisomer. This method is suitable for routine quantification of labetalol diastereoisomers and has been applied to a pharmacokinetic study in small laboratory animals.