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Biomedical subjects

M Audran

Publications and source records attributed to M Audran.

At least 55 records · Page 3Linked to original sources
PubMed1998

Reversed-phase high-performance liquid chromatographic determination of enoxacin and 4-oxo-enoxacin in human plasma and prostatic tissue. Application to a pharmacokinetic study.

A simple high-performance liquid chromatographic method has been developed for the simultaneous determination of enoxacin and 4-oxo-enoxacin in plasma and prostatic tissue. The work-up procedure involves a liquid-liquid extraction step followed by isocratic chromatography on a reversed-phase analytical column, with ultraviolet absorbance detection (lambda = 340 nm). Using a mobile phase of 20.9% (v/v) acetonitrile buffer (pH 2.1), adequate retention time and separation among the analytes has been obtained using tetrabutylammonium hydroxide included in the eluent. Retention times are 5.2 min for enoxacin, 6.8 min for pefloxacin and 12 min for 4-oxo-enoxacin. For plasma and prostatic tissue, the precision of the assay was below 9%. The percent recovery from the nominal values for accuracy ranged from 94 to 108%. The limits of quantitation were 20 ng/ml for plasma and 50 ng/g for tissue (precision < 18%). The detection limits were 10 ng/ml and 25 ng/g, respectively. The calibration curves were linear from 20 to 1000 ng/ml for plasma and from 50 to 2500 ng/g for tissue. In plasma, the extraction recoveries averaged 52% for enoxacin and 63% for 4-oxo-enoxacin. In prostatic tissue, they were 57 and 76% for the two analytes, respectively. This method has been employed for the determination of enoxacin and 4-oxo-enoxacin in plasma and prostatic tissue samples from patients following repeated oral administration of enoxacin (400 mg twice a day for four days).

Adenoma↗
PubMed1998

Increased nucleolar organizer regions in osteoclast nuclei of Paget's bone disease.

The etiology of Paget's disease of bone is still unknown but several studies have reported a viral origin. At the electron microscopic level, characteristic nuclear and cytoplasmic inclusions have been found and mimic paramyxoviral nucleocapsids in osteoclasts (Oc). Sarcomatous degeneration is observed in 2% of pagetic patients. Nuclear organizer regions are parts of the nucleolus involved in the synthesis of ribosomes, and they contain nonhistone proteins that can be silver stained (AgNORs) on the interphasic nuclei. AgNOR number is known to correlate with the proliferative activity of the cell populations, whether normal or malignant. Cancer cells have an increased demand for (robosomal) rRNA and correlations have been found between AgNORs and proliferative antigens. We have adapted the AgNOR staining method to undecalcified bone biopsies at the light and TEM levels. Bone sections from 10 pagetic patients (without a previous bisphosphonate treatment) were stained for AgNORs. 10 patients having metabolic bone diseases associated with an increased Oc number (i.e., primary and secondary hyperparathyroidism) were used as controls. AgNORs appeared as black dots within the nucleoli of Oc nuclei and were easily numbered. A maximum of two or three dots could be seen in Oc nuclei from control subjects. In pagetic Oc, AgNOR number was greatly increased (6.80 +/- 2.57 dots vs. 2.12 +/- 1.07 in controls). TEM study also showed AgNOR in the nucleoli of pagetic patients' Oc. The viral inclusions within the nuclei appeared faintly stained and could not be confused with AgNORs. The large number of AgNORs in the nuclei of pagetic Oc reflects the need for a greater abundance of ribosomes. With the pagetic Oc being highly active, the cytoplasmic synthesis of proteins is maximized (probably hydrolases involved in the matrix breakdown). An increase in AgNORs does not reflect the proliferative activity of the cell because Oc are made by the fusion of precursors. It is postulated that: (a) other mRNAs (of viral/oncogene origin) could be actively transcribed in pagetic patients and require more numerous ribosomes; or (b) a viral genome/oncogene promotes alteration of the nuclear/nucleolar mechanism.

Cell Nucleus↗
PubMed1998

Different patterns of extension and recurrence in algodystrophy.

A true recurrence at exactly the same site is quite unusual in algodystrophy. Local or regional extension is possible. The bone scan is an easy way to demonstrate that the areas successively affected are not the same. An apparent local recurrence could in fact be a microscopic compression fracture of trabecular bone or cortical fractures or part of a factitious disorder.

Adult↗
PubMed1998

Further vascular, bone and autonomic investigations in algodystrophy.

Direct clinical observation is the most common means of diagnosing algodystrophy. Further investigations may be helpful to rule out other pathological conditions, such as occult or stress fractures or avascular osteonecrosis and to obtain a better understanding of algodystrophy. Transient vascular hyperpermeability in the affected part is well demonstrated by the clinical findings, the MRI signs, and the three-bone scan features. 99m Technectium EHDP bone scan provides an evaluation of the vascular abnormalities and of the osteoblastic activity. Dermal microcirculation and its reactions to sympathetic stimuli are investigated by laser doppler fluximetry and videophotometric capillaroscopy. Perhaps the sweat test does unveil what might be specific about algodystrophy. The amount of bone loss in algodystrophy in a few weeks or months is what might be expected over 10 years during the natural history of uncomplicated osteoporosis. An initial fracture is undoubtedly an initiating event in the appearance of algodystrophy, but patients suffering from algodystrophy may still have significant osteoporosis for a long period and hence be at risk for fracture. Densitometry could be an aid to the diagnosis and probably to monitoring treatment as well. The local colonization of fibroblasts following the transient stage of hyperpermeability must be kept in mind to explain the results of joint, bone, muscles or neurological investigations in late algodystrophy.

Absorptiometry, Photon↗
PubMed1997

Determination of nalbuphine in human plasma by high-performance liquid chromatography with electrochemical detection. Application to a pharmacokinetic study.

A high-performance liquid chromatographic procedure has been developed for the measurement of nalbuphine in plasma. Separation is performed on a reversed-phase analytical column (Ultrasphere ODS, 250 x 4.6 mm I.D., particle size, 5 microns). Mobile phase consisted of methanol-phosphate buffer (20:80, v/v) (pH 3.4). Electrochemical detection was performed using an ESA Coulochem II Model 5200 electrochemical detector equipped with a Model 5020 guard cell working at 550 mV and a Model 5021 analytical cell operating in the oxidation screening mode, with the potential of the first electrode set at 60 mV and the second electrode set at 450 mV. The method involves sample clean-up by liquid-liquid extraction using a chloroform-isopropanol mixture. After centrifugation, the organic phase was back-extracted with 17 mM phosphoric acid and then the aqueous phase was injected onto the column. The limits of quantitation and detection were 0.3 and 0.1 ng/ml, respectively. The extraction recovery was 91.1 +/- 3.7%. The intra- and inter-assay coefficients of variation were below 10%. Stability tests under various conditions have been performed. This method has been used to determine the pharmacokinetic parameters of nalbuphine in children.

Analgesics, Opioid↗
PubMed1997

Comparison of a direct and indirect population pharmacodynamic model: application to recombinant human erythropoietin in athletes.

Basic physiologic indirect response models have been proposed to account for the pharmacodynamics of drugs that act by way of inhibition or stimulation of the production or loss of endogenous substances or mediators. In this work, these models were applied to account for the effects of recombinant human erythropoietin (rHuEpo) in man. Indeed, rHuEpo induces a delayed increase of serum soluble transferrin receptors (sTfr) and a delayed decrease in ferritin (fr) concentrations. The purpose of the present study was to compare two pharmacodynamic approaches to relate serum erythropoietin (Epo) concentrations to the effect of rHuEpo on sTfr, and fr, the "indirect effect" and the "effect compartment" models. However, due to the average lag time of about 50 hr between the first intake of rHuEpo and the onset of the measurable effects, a delay function was incorporated into the "indirect response models" to describe the relationship between the Epo plasma concentrations and the endogenous receptors or mediators affected by the drug and responsible for the effects on sTfr and fr. There are no real differences in the descriptive features of the two models used. For these reasons, the indirect model seems more appropriate because it supplies a possible mechanistic interpretation of the physiological process.

Adult↗
PubMed1997

Progression in length and width of pagetic lesions, and estimation of age at disease onset.

The mean annual rate of increase in the length of pagetic lesions was 8.5 mm for the skull and tibia and 9.4 mm for the femur, after a follow-up of nine to 16 years according to the bone. The fastest rate of progression was seen at the femur and was 24 mm per year. Thirty years were required for lesions to spread to the entire pelvis and 13 years to all the bones surrounding the obturator foramen. Saber shin deformity of the tibia without involvement of the distal fourth of the bone indicated a disease duration of 25 years, as did involvement of the entire skull. The annual rate of increase in the width of lesions varied widely across patients and was not influenced by gender. Thickening of the skull occurred at a rate of about 4 to 5 mm per decade after pagetization of the bone, although faster rates were seen in some patients; a sandwich-like appearance with a thickness exceeding 32 mm was seen in six of the 29 skulls studied. At the femur and tibia, the increase in width was 10% to 30% per decade after pagetization of the bone; faster thickening was seen in some tibias with saber shin deformity. The thickness of the ischial tuberosity increased by 3 to 4 mm per decade after pagetization. Determination of the degree of hypertrophy is useful for estimating the duration of pagetic lesions when the entire bone is involved at first presentation. Involvement of the entire pelvis indicates a disease duration of 30 to 40 years according to whether the bone is hypertrophied or not. An estimation of age at disease onset in 70 patients suggested that the first bone lesions probably appeared before the age of 30 years in 45 patients (64%), whereas the diagnosis was established before 30 years in only three patients. These data suggest that Paget's disease may be a disease of teenagers and young adults.

Adult↗
PubMed1997

Polyostotic Paget's disease. A search for lesions of different durations and for new lesions.

We conducted a medical record-based study of 169 patients with polyostotic involvement identified among 200 Paget's disease patients. Follow-up was 15 to 41 years in 31 cases. The pelvis was the only bone that was more likely than not to be involved bilaterally. All the other paired bones were more likely to be involved unilaterally and when both sides were involved the two lesions were very often frankly asymmetric. In a given patient, the duration of the various pagetic lesions, estimated from their size and from data provided by an earlier study on the rate of progression of pagetic lesions, was similar in some cases and showed marked differences in others. Aggregation of the lesions into two or three disease duration groups was seen in some patients, suggesting that Paget's disease may occur in two or three waves. When we reviewed the radiographs from 30 patients with a mean follow-up of 23 years, we found new lesions in ten patients. However, a review of bone scans from 18 patients with a mean follow-up of 11 years failed to uncover any firm evidence of new lesion development, perhaps because all these patients received bisphosphonate therapy (etidronate, tiludronate, pamidronate). We also found data suggesting that the disease process spread across a joint in some patients, even in the absence of degenerative joint disease. In particular, in several cases an extensive pagetic lesion was seen on one side of a joint and a considerably smaller lesion on the other side.

Adult↗
PubMed1997

Epidural involvement in nontuberculous disk space infections. Incidence by magnetic resonance imaging, impact and prognosis.

Eleven of 25 patients admitted for nontuberculous disk space infections had magnetic resonance imaging evidence of epidural infection. No differences were found between the 11 patients with and the 14 patients without epidural infection regarding time to diagnosis, height of fever, presence of nerve root pain, presence of prespinal and/or paraspinal abscesses and proportion of cases due to Staphylococcus aureus. Antimicrobial therapy alone ensured a full recovery with no neurological sequelae in most cases, suggesting that presence of epidural sepsis does not affect the prognosis of nontuberculous disk space infections.

Abscess↗
PubMed1996

Cyclodextrins and enantiomeric separations of drugs by liquid chromatography and capillary electrophoresis: basic principles and new developments.

Investigation of individual drug enantiomers is required in pharmacokinetic and pharmacodynamic studies of drugs with a chiral centre. Cyclodextrins (CDs) are extensively used in high-performance liquid chromatography as stationary phases bonded to a solid support or as mobile phase additives in HPLC and capillary electrophoresis (CE) for the separation of chiral compounds. We describe here the basis for the liquid chromatographic and capillary electrophoretic resolution of drug enantiomers and the factors affecting their enantiomeric separation. This review covers the use of CDs and some of their derivatives in studies of compounds of pharmacological interest.

Chemistry, Pharmaceutical↗
PubMed1996

Validation of liquid chromatographic and gas chromatographic methods. Applications to pharmacokinetics.

Validations of analytical methods are important for the generation of data for bioavailability, bioequivalence and pharmacokinetic studies. It is essential to use well defined and fully validated analytical methods to obtain reliable results that can be satisfactorily interpreted. This manuscript is intended to provide guiding principles for the evaluation of a method's overall performance. For this purpose, all of the variables of the method are considered, including sampling procedure, sample preparation, chromatographic separation, detection and data evaluation. The criteria considered are as follows: stability, selectivity, limits of quantification and of detection, accuracy, precision, linearity, recovery and ruggedness. Models used for analytical calibration curves are explained in term of validity and limitations, along with a presentation of the most common statistical considerations used to validate the model. Appropriate means of testing precision and accuracy, the most important factors in assessing method quality, are presented. Other issues, such as re-validation, cross-validation, partial sample volume, endogenous drugs and biological matrix of limited availability, are also discussed.

Calibration↗
PubMed1996

[Current options for the treatment of Paget's disease of bone].

From 10 to 20% of patients with Paget's disease of bone, including those without patent clinical signs, risk severe neurological, orthopedic or cardiovascular complications. Calcitonin and etidronate were the first drugs allowing a certain degree of control over excessive bone remodeling subsequent to Paget's disease. Further progress has been made with a family of new bisphosphonates (clodronate, pamidronate, tiludronate, alendronate, risedronate, and others). Ideally, treatment should eliminate bone pain, normalize markers, restore normal bone structure, and prevent recurrence and complications. The new generation of bisphosphonates have powerful anti-osteoclasic activity. These easy-to-administer well-tolerated drugs may be indicated in certain asymptomatic patients in the 50-year age range who have active disease and lesions involving the skull (neurological risk) or lower limbs (orthopedic risk). Although there are no data on the cost effectiveness comparing medical or surgical treatment in these forms having reached the stage of complications, the result in terms of pain relief and improved quality of life is real. Further assessment of wider indications for certain non-symptomatic, but threatening forms of the disease, is needed. Prospective studies should focus on medical improvement, quality of life, and cost-effectiveness.

Diphosphonates↗
PubMed1996

High-performance liquid chromatographic determination of tazobactam and piperacillin in human plasma and urine.

A high-performance liquid chromatographic (HPLC) method with ultraviolet (UV) absorbance was developed for the analysis of piperacillin-tazobactam (tazocillin), in plasma and urine. The detection was performed at 218 nm for tazobactam and 222 nm for piperacillin. The procedure for assay of these two compounds in plasma and of piperacillin in urine involves the addition of an internal standard (ceftazidime for tazobactam and benzylpenicillin for piperacillin) followed by a treatment of the samples with acetonitrile and chloroform. To quantify tazobactam in urine, diluted samples were analysed using a column-switching technique without internal standard. The HPLC column, LiChrosorb RP-select B, was equilibrated with an eluent mixture composed of acetonitrile-ammonium acetate (pH 5). The proposed technique is reproducible, selective, and reliable. The method has been validated, and stability tests under various conditions have been performed. Linear detector responses were observed for the calibration curve standards in the ranges 5-60 micrograms/ml for tazobactam, and 1-100 micrograms/ml for piperacillin and spans what is currently though to be the clinically relevant range for tazocillin concentrations in body fluids. The limit of quantification was 3 micrograms/ml for tazobactam and 0.5 microgram/ml for piperacillin in plasma and urine. Extraction recoveries from plasma proved to be more than 85%. Precision, expressed as C.V., was in the range 0.4-18%.

Chromatography, High Pressure Liquid↗