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Biomedical subjects

C Lefèvre

Publications and source records attributed to C Lefèvre.

At least 19 recordsLinked to original sources

Determination of ivabradine and its N-demethylated metabolite in human plasma and urine, and in rat and dog plasma by a validated high-performance liquid chromatographic method with fluorescence detection.

A sensitive and selective high-performance liquid chromatographic method with native detection of fluorescence was developed and validated for the quantitation of ivabradine and its N-demethylated metabolite in plasma (rat, dog, human) and human urine. The procedure involves the use of an analogue as internal standard, solid-phase extraction on cyano cartridges, separation on a Nova-Pak C8 column and fluorescence detection. Calibration curves are linear in the concentration ranges from 0.5 to 100 ng/ml in plasma and 2.0 to 500 ng/ml in urine with a limit of quantitation set at 0.5 and 2.0 ng/ml in plasma and urine, respectively. The analysis of plasma and urine samples (spiked with the analytes at low, medium and high concentrations of the calibration range) demonstrates that both analytes can be measured with precision and accuracy within acceptable limits. Quality controls spiked with analyte concentrations up to 10000 ng/ml can also be analysed with excellent precision and accuracy after dilution of the samples. The parent drug and its metabolite are stable in plasma and urine after short-term storage (24 h at room temperature and after three freeze-thaw cycles) as well as after long-term storage at -20 degrees C (at least 6 months in animal plasma and 12 months in human plasma and urine). The method has been used to quantify both compounds in plasma and urine samples from clinical and non-clinical studies with ivabradine.

Animals

Arterial and neural relations at the posterior and lateral aspects of the medullo-spinal junction.

The authors report the results of a series of 59 microdissections of the region of the foramen magnum. These dissections were made under the strict conditions of a surgical approach using an operating microscope. The major anatomic structures of the medullo-spinal junction are arranged mainly at its lateral aspect. The customary surgical approaches to the posterior cranial fossa give ready access to the cerebello- and latero-medullary cisterns. The description of the neurovascular structures contained therein assumes a particular importance because of the relative frequency of lesions developing at this level. This study deals particularly with the vertebral a. (VA), the inferior posterior cerebellar a. (IPCA), the cranial nn. IX (glossopharyngeal n.), X (vagus n.), XIc and XIs (cranial and spinal accessory n.) and XII (hypoglossal n.). The anatomy of this posterior and lateral region is characterised by the contrast between the relatively uniform course of the VA and the variable course of the IPCA, a true guideline whose very irregular arrangement accounts for the diversity of its relations with the last four cranial nn.

Cadaver

[Static and dynamic changes of the cervical spine after laminectomy for cervical spondylotic myelopathy].

PURPOSE OF THE STUDY: Extensive cervical laminectomy has been widely used in the treatment of progressive myelopathies secondary to stenotic conditions. Complications of this procedure such as spinal instability, accelerated spondylotic changes, postoperative spinal deformity and constriction of the dura mater by extradural scar tissue formation have been recognized. However, the frequency of these complications is probably overestimated and their consequences on the clinical outcome remain unknown. The purpose of this report was to describe the incidence and consequences of cervical spinal deformity and instability after multilevel laminectomy in adult patients with myelopathy caused by cervical spondylosis and to determine the usefulness of preoperative dynamic films in the prevention of postoperative destabilization. MATERIALS AND METHODS: 30 patients older than 30 years who underwent a laminectomy of more than 3 levels without fusion for myelopathy secondary to cervical spondylosis were reviewed retrospectively with an average follow-up of 5 years. Functional results were evaluated according to the Japanese Orthopaedic Association scoring system. Lateral views in neutral position, in flexion and in extension of the preoperative cervical roentgenograms were analyzed in comparison with the last follow-up one in order to identify the changes in the curvature of the cervical column, in the range of motion of the neck, in the intervertebral angular mobility and antero-posterior displacement of the vertebral bodies, and finally to identify the incidence of spinal instability. RESULTS: 18 patients (31 per cent) developed postoperative changes in cervical spine curvature. 15 patients (25 per cent) had one or more destabilized levels. Deformities of the cervical spine occurring after surgery do not appear to cause any symptom or neurologic abnormalities. Destabilization required repeat surgery in 3 patients. All the levels found destabilized on the postoperative films were hypermobile on the preoperative dynamic radiographs. A preoperative olisthesis without hypermobility was not a risk factor for postoperative destabilization. CONCLUSION: The use of preoperative dynamic radiographs should improve the selection of patients undergoing laminectomy for the treatment of multilevel cervical cord compression. Dynamic X-rays may also reinforce the need for possible adjunctive procedures such as fusion and instrumentation, in order to prevent a postoperative destabilization. A preoperative olisthesis with a hypermobility in sagittal or horizontal planes must be fused and instrumented.

Aged

Detection of herpes simplex DNA in semen and menstrual blood of individuals attending an infertility clinic.

OBJECTIVE: To determine a possible link between herpes simplex virus 1 (HSV) and infertility. METHOD: A specifically designed polymerase chain reaction with nested primers, was developed and used to test for HSV in 153 men and 20 women attending an infertility clinic. RESULTS: HSV DNA was detected in 37 (24%) out of 153 semen samples and in 11 (55%) out of 20 menstrual blood samples. However, HSV DNA (0%) was not detected in the semen of 16 males with children. A significant association between the evidence for infertility and an HSV positive test was observed in men (Fisher's exact test, p = 0.024), and a stronger effect was found in females after failed in vitro fertilization (Fisher's exact test p = 0.0086). CONCLUSION: This is the first report of the detection of herpes simplex virus DNA in semen and menstrual blood. Encouraging preliminary results justify antiviral therapy in case of a positive test.

Acyclovir

Collective epidemic models.

A number of models have been proposed to describe the spread of infectious diseases of the S-I-R type. Most of them account for variable infectivity levels, and very few incorporate variable susceptibility levels. In the present work, a new epidemic model, called a collective model, is constructed that combines both variabilities in a general way. It is then established how to determine the exact distribution of the final state and the severity of the epidemic when the infection process stops.

Communicable Diseases

[Therapeutic possibilities of the lateral supra-malleolar flap and its variations. Apropos of 6 clinical cases].

The distally based lateral supramalleolaire flap with a retrograde blood flow on the perforating branch of the peroneal artery is a good flap to treat loss of skin involving the ankle, the region behind the Achilles tendon, and the foot. Based on the results of an anatomical study, the authors describe a modification of this flap which can be raised on the infero-lateral collateral artery, with an anterograde blood flow. In fact, clinical experience of six cases shows that vascular pedicle component (perforating branch of the peroneal artery, infero-lateral collateral artery) and blood flow (anterograde, retrograde) can be calculated according to the regional vascular network, arc of rotation and the type of flap. Because of the many possible combinations, it can be considered to be a flap with variable vascular pedicle raised "à la carte". However, according to our clinical cases, the anterograde blood flow does not seem to have resolved the problems of venous congestion of this flap.

Adult

Internal motions of apo-neocarzinostatin as studied by 13C NMR methine relaxation at natural abundance.

Dynamics of the backbone and some side chains of apo-neocarzinostatin, a 10.7 kDa carrier protein, have been studied from 13C relaxation rates R1, R2 and steady-state 13C-(1H) NOEs, measured at natural abundance. Relaxation data were obtained for 79 nonoverlapping C alpha resonances and for 11 threonine C beta single resonances. Except for three C alpha relaxation rates, all data were analysed from a simple two-parameter spectral density function using the model-free approach of Lipari and Szabo. The corresponding C-H fragments exhibit fast (tau e < 40 ps) restricted libration motions (S2 = 0.73 to 0.95). Global examination of the microdynamical parameters S2 and tau e along the amino acid sequence gives no immediate correlation with structural elements. However, different trends for the three loops involved in the binding site are revealed. The beta-ribbon comprising residues 37 to 47 is spatially restricted, with relatively large tau e values in its hairpin region. The other beta-ribbon (residues 72 to 87) and the large disordered loop ranging between residues 97-107 experience small-amplitude motions on a much faster (picosecond) time scale. The two N-terminal residues, Ala1 and Ala2, and the C-terminal residue Asn113, exhibit an additional slow motion on a subnanosecond time scale (400-500 ps). Similarly, the relaxation data for eight threonine side-chain C beta must be interpreted in terms of a three-parameter spectral density function. They exhibit slower motions, on the nanosecond time scale (500-3000 ps). Three threonine (Thr65, Thr68, Thr81) side chains do not display a slow component, but an exchange contribution to the observed transverse relaxation rate R2 could no be excluded at these sites. The microdynamical parameter (S2, tau e and R2ex) or (S(slow)2, S(fast)2 and tauslow) were obtained from a straightforward solution of the equations describing the relaxation data. They were calculated assuming an overall isotropic rotational correlation time tau c for the protein of 5.7 ns, determined using standard procedures from R2/R1 ratios. However, it is shown that the product (1-S2) x tau e is nearly independent of tau c for residues not exhibiting slow motions on the nanosecond time scale. In addition, this parameter very closely follows the heteronuclear NOEs, which therefore could be good indices for local fast motions on the picosecond time scale.

Apoproteins

A fast word search algorithm for the representation of sequence similarity in genomic DNA.

Representation of sequence similarity by dot matrix plots is a method widely used for comparing biological sequences. The user is presented with an overall view of similarity between two sequences. Computation of this plot has been reconsidered here. An improvement is proposed through the preprocessing of the data into an automation recognizing the word structure of a sequence. The main advantage of this approach is to systematically eliminate the repetitions during word comparison. Simple heuristics are also considered to greatly speed up pattern matching. As a result, large sequences are handled very efficiently. This is illustrated by a comparison of large genomic DNA. The algorithm has been implemented in an interactive application on a microcomputer.

Algorithms

The "anatomic" view of the suprarenals in medical imaging.

Based on coordinates derived from three series of anatomic sections, the authors propose a view for tomographic investigation, applicable in MRI and ultrasound, which reconstructs the ideal image of the suprarenal gland in its quadrilateral as described by Testut. This "anatomic" view is 45 degrees vertical and oblique, intermediate between the sagittal and frontal views, which it can advantageously replace. A new aspect of suprarenal tomography, recalling the image of a triskele, is described in the context of this view.

Adrenal Glands

The position end-set tree: a small automaton for word recognition in biological sequences.

We consider the basic function which locates a specific string of symbols within a longer sequence. When one is expecting to do many substring searches it is worthwhile to build an auxiliary index to the sequence to aid in the search. We propose a method to generate a compact index that can be viewed as a small (partial) deterministic finite automaton recognizing the subword structure of a sequence. We present an algorithm for its construction on-line in linear time. Such a data structure permits the efficient localization of subwords in a sequence and can be used in the development of interactive sequence analysis software.

Algorithms

Pattern recognition in DNA sequences and its application to consensus foot-printing.

We consider the problem of comparing several nucleic acid sequences to identify words occurring imperfectly (patterns with no gap) with unusual frequency. Methods for computing, representing, and inspecting interactively the structure of such repeating motifs in nucleic acids and more generally any text are described. Multiple sequences are treated as one large concatenate. In a preprocessing step, a lexical index is created to provide rapid string matching for the enumeration of the words matching a pattern. For given word features (word length, minimal frequency), a sequence profile is displayed. The profile can be inspected interactively with on-line algorithms. Applications to the identification of regulatory elements in DNA regions involved in the control of gene expression are presented. Our program ('DNA-Lexemics') runs on the Macintosh.

Algorithms

A small automaton for word recognition in DNA sequences and its application to consensus analysis of regulatory elements in DNA regions controlling gene expression.

A method for pattern analysis of DNA sequence data is considered. A space economical automaton for word recognition was presented elsewhere together with an algorithm for its compilation in linear time. An algorithm for the localization of words including imperfect matches (motif search) was developed. A program was implemented on the Macintosh and used extensively for the representation of the word composition of DNA data. We explore different sets of regulatory sequences to illustrate the performance of this method. In mammalian DNA, this analysis reveals "consensus motifs" corresponding to functional (or putative) cis-acting elements mediating the regulation of gene expression.

Algorithms

The dimension of Reed-Frost epidemic models with randomized susceptibility levels.

A generalized Reed-Frost epidemic process is discussed in which variability among susceptible individuals is incorporated by randomizing the levels of resistance of the individuals to the infection. Our purpose is to derive the exact distribution of the ultimate number of susceptibles surviving the disease. This is achieved by a simple conditional argument and by using a particular family of polynomials defined recursively. The results can be viewed as a continuation of those obtained by the authors for the alternative situation with randomized infectivity levels.

Disease Outbreaks

Measuring the severity of disease clustering using Tango's index.

Tango [Biometrics 40:15 (1984)] proposed an index for detecting disease clustering in time applicable to grouped data obtained from a population that remains fairly stable over the study period. This index has received considerable attention in the literature including the suggestion that it be used to detect the space-time clustering of diseases and the suggestion to use similar test statistics to detect disease clustering in space and/or time while accounting for a changing population size over the study period. This paper concerns the related question of measuring the severity of the disease clustering once it has been determined that cases are not randomly distributed over space and/or time. A family of alternatives to randomness is proposed in which space and/or time versions of Tango's index are sufficient statistics for the parameters measuring the severity of the clustering. For the special case of temporal clustering, an unbiased estimator of the clustering parameter and its sampling variance is derived, and a particularly simple interpretation of this estimator is suggested. These latter results are based on some asymptotic approximations due to Tango [Biometrics 46:351 (1990)]. An application to the trisomy data given by Wallenstein [Am. J. Epidemiol. 111:367 (1980)] is discussed.

Cluster Analysis

A mathematical model of rinderpest infection in cattle populations.

A mathematical model for the epidemiology of rinderpest was developed, starting from a simplified descriptive analysis of the disease. A formula for the calculation of the probability of infection of a susceptible animal was first established. A deterministic failure threshold of the infection was then deduced. Deterministic and stochastic approaches were adopted using iterative methods on a computer. These allowed a description of the spread and the variability of an infection process in a population to be made. An illustration of the use of this model showed that, in some cases, variability effects due to stochastic factors were very important. In these particular conditions, the use of the deterministic model alone was not adequate for a good description of the infection. Consequently, improvements of the model were proposed in order to make it more realistic and to allow its use for the evaluation of the efficiency of field operations.

Animals

[3-dimensional reconstruction of x-ray computed tomographic views in fractures of the acetabulum].

In 21 cases of acetabulum fractures of 19 patients, the authors compare the findings given by three dimensional reconstructions of axial CT scan cuts with the plain films. The number of CT scan cuts is reasonable for each patient. Working time is about 20 to 30 minutes for the technician. In the cases of complex and displaced fractures, three dimensional imaging brings often decisive informations for the therapeutic management of these patients. Unusual views are often allowed but completely adapted to each type of fracture.

Acetabulum

[A proposed prototype for recording and analysis of mandibular movement: the Cinétic].

The investigation of means of recording mandibular movement has aroused the interest of a considerable number of researchers. Their own devices, increasingly ingenious, all display certain advantages and shortcomings. The need for a device more appropriate to the needs of day-to-day odontological use has been felt for some time. By giving a broad explanation of how it works, we have tried to assess the possibilities of the proposed prototype, the Cinetic. It measures movement of the dentalium in all three dimensions simultaneously. Since its reliability, when tested by a study concerning a sample of 40 patients, proved entirely satisfactory, a more sophisticated version was promptly devised. This latest Cinetic allows the ROZENCWEIG dyskinesia index, to be calculated, the FARRAR diagram to be drawn, and the mastication movements to be analysed by giving a visual display of the mandibular opening and closing trajectories, the speed diagram, the duration of the cycle, mandibular velocity and acceleration, and a breakdown of the cycles for each respective side. In order to be fully competitive, the Cinetic lacks the capacity to record and analyse condylar movement. Work on incorporating these features is currently at an experimental stage.

Dental Equipment