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Biomedical subjects

F Leitner

Publications and source records attributed to F Leitner.

At least 19 recordsLinked to original sources

Computer assisted knee replacement.

Accurate alignment of knee implants is essential for the success of total knee replacement. Although mechanical alignment guides have been designed to improve alignment accuracy, there are several fundamental limitations of this technology that will inhibit additional improvements. Various computer assisted techniques have been developed to examine the potential to install knee implants more accurately and consistently than can be done with mechanical guides. For example, computer integrated instrumentation incorporates highly accurate measurement devices to locate joint centers, track surgical tools, and align prosthetic components. Image guided knee replacement provides a three-dimensional preoperative plan that guides the placement of the cutting blocks and prosthetic components. Robot assisted knee replacement allows one to machine bones accurately without the use of standard cutting blocks. The rationale for the development of computer assisted knee replacement systems is presented, the operation of several different systems is described, the advantages and disadvantages of different approaches are discussed, and areas for future research are suggested.

Arthroplasty, Replacement, Knee

In vitro dynamics of chromatin organization and migration.

The organization of eukaryotic chromatin is not static but changes as a function of cell status during processes such as proliferation, differentiation, and migration. DNA quantification has not been used extensively to investigate chromatin dynamics in combination with cellular migration. In this context, an optimized DNA-specific, nonperturbant method has been developed for studying chromatin organization, using the fluorescent vital bisbenzimidazole probe Hoechst 33342: this property has been described by Hamori et al. (1980). Computer-assisted image analysis was used to follow migratory activity and chromatin organization of L929 fibroblasts during in vitro wound healing. Cell movements were analyzed using an optical flow technique, which consists in the calculation of the velocity field of cells and nuclear movements in the frame. This system allows the correlation of cell migration and position in the cell cycle. It makes it possible to study chromatin dynamics using a quantitative analysis of nuclear differentiation reorganization (nuclear texture) and to correlate this with migration characteristics. The present system would be of interest for studying cell-extracellular matrix interactions using differing substrates, and also the migratory response to chemotactic factors. Such a model is a prerequisite for gaining better understanding of drug action.

Animals

Dynamic functional and structural analysis of living cells: new tools for vital staining of nuclear DNA and for characterisation of cell motion.

Increasing interest has been paid to applications of fluorescence measurements to analyze physiological mechanisms in living cells. However, few studies have taken advantage of DNA quantification by fluorometry for dynamic assessment of chromatin organization as well as cell motion during the cell cycle. This approach involves both optimal conditions for DNA staining and cell tracking methods. In this context, this report describes a stoichiometric method for nuclear DNA specific staining, using the bisbenzimidazole dye Hoechst 33342 associated with verapamil, a calcium membrane channel blocker. This method makes it possible to correlate variations of nuclear DNA content with cell motion in cells that are maintained alive. Motion measurement is the second goal of this paper and it explains the snake-spline method, and the associated cell following method.

Animals

Interpretation of multimodal medical images using connectionist and variational methods.

Our medical objective is to match multimodal 3D medical images into a coherent model of the patient, from which diagnosis can be assessed and therapeutics guided. 3D image segmentation is absolutely necessary to reach this objective. We investigate two complementary approaches for segmenting 3D medical images. First we present some definitions, basic properties and recent theoretical results about formal neural networks, and show that these results can be applied to brain tumour segmentation. A variational approach (called the 'snake spline' method) is then detailed. We finally show how segmented 3D images can be used for multimodal image matching.

Algorithms

[Dynamic characterization of the growth of brain tumors based on image sequences of nuclear magnetic resonance].

The evolution of a high grade glioblastoma of a patient undergoing radio-therapy has been analysed by considering a mathematical model which simulates the brain tumour growth within a two-dimensional domain defined by the brain and ventricles geometry. This simulated behaviour was compared with morphological data obtained from successive nuclear magnetic resonance scans of the patient. The model parameters include the proliferation rate and the diffusion coefficient of the tumour cells as well as their sensitivity to the irradiation. They were estimated using optimisation techniques to minimise the distance between simulated tumour area and scan data from different brain sections. The relevance of this quantitative estimation for the prognosis and for the consideration of additional parameters in the pre and post therapeutic evaluation of glioma is discussed.

Brain

Therapeutic studies of cefepime (BMY 28142) in murine meningitis and pharmacokinetics in neonatal rats.

Cefepime (BMY 28142) was compared with ceftazidime, cefotaxime, and moxalactam for efficacy in treating experimental meningitis in mice and neonatal rats. Mice were infected intracranially with Streptococcus pneumoniae, S. agalactiae, Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa and treated intramuscularly. Five- to eight-day-old neonatal rats were injected intracisternally with Haemophilus influenzae, S. pneumoniae, and S. agalactiae and treated intraperitoneally. Cefepime was found to be the most active compound against induced meningitis in mice infected with S. agalactiae. Cefepime was as active as cefotaxime against Staphylococcus aureus meningitis, slightly more active than cefotaxime against S. pneumoniae and E. coli, and as active as ceftazidime against K. pneumoniae and P. aeruginosa meningitis. Cefepime was found to be the most active compound against S. pneumoniae and S. agalactiae meningitis in neonatal rats. Against H. influenzae, cefepime was as active as moxalactam and cefotaxime. Ceftazidime was the least active compound. The pharmacokinetics of cefepime in neonatal rats were similar to those of ceftazidime. Both compounds penetrated well into cerebrospinal fluid and brain tissues of uninfected neonatal rats. Relative concentrations were twice as high as those of cefotaxime and moxalactam.

Animals

BMY 28100, a new oral cephalosporin.

BMY 28100, a new oral cephalosporin with a (Z)-propenyl side chain at the 3 position and a p-hydroxyphenylglycyl substituent at the 7 position, was evaluated in comparison with cefaclor and cephalexin and, when appropriate, ampicillin and vancomycin. In vitro, BMY 28100 was more active than the reference cephalosporins against streptococci, Staphylococcus aureus, Staphylococcus epidermidis, Listeria monocytogenes, Haemophilus influenzae, Propionibacterium acnes, Clostridium perfringens, and Clostridium difficile. BMY 28100 was comparable to cefaclor and more active than cephalexin against Staphylococcus saprophyticus and ampicillin-susceptible strains of Branhamella catarrhalis; but against ampicillin-resistant strains of B. catarrhalis, BMY 28100 was comparable to cephalexin and more active than cefaclor. Against Neisseria gonorrhoeae, BMY 28100 was comparable to cephalexin, but less active than cefaclor. Members of the family Enterobacteriaceae overall were equally susceptible to BMY 28100 and cefaclor but were less susceptible to cephalexin. In human serum, BMY 28100 was 45% protein bound. After an oral dose to mice, 82% of the drug was recovered in urine. The oral therapeutic efficacy of BMY 28100 in systemically infected mice reflected its activity in vitro.

Animals

Comparison of a new cephalosporin, BMY 28142, with other broad-spectrum beta-lactam antibiotics.

BMY 28142, a new broad-spectrum semisynthetic cephalosporin, was evaluated in vitro and in vivo in comparison with ceftazidime, cefotaxime, moxalactam, and cefoperazone. The activity of BMY 28142 compared favorably with the activities of the other compounds against both Pseudomonas aeruginosa and Staphylococcus aureus and was somewhat greater against members of the family Enterobacteriaceae. The influence of inoculum size on MICs of BMY 28142 was small for most of the isolates tested, except Enterobacter species. With Enterobacter strains, a marked inoculum effect was found with all of the compounds, and the effect was more pronounced in broth than agar. Still, MICs of BMY 28142 in broth did not exceed 16 micrograms/ml. Of 37 Enterobacteriaceae strains resistant to one or more of the comparison beta-lactams, none were resistant, at a low inoculum size (10(4) CFU), to BMY 28142, compared with 3 for moxalactam, 18 for ceftazidime, 23 for cefotaxime, and 34 for cefoperazone; at an inoculum size of 10(6) CFU, the number of resistant strains was 12, 17, 25, 34, and 37, respectively. Binding to human serum proteins approximated 19%. Recovery of 73% of the drug in mouse urine indicated good bioavailability. The in vitro profile was sustained in vivo by the results obtained with experimental infections in mice. BMY 28142 was as effective as ceftazidime against systemic infection with P. aeruginosa and as effective as cefotaxime against systemic infection with S. aureus. Overall, infections with 18 of 20 strains representing nine genera were responsive to BMY 28142 at doses equivalent to or lower than those of the most effective of the comparison compounds.

Animals

Antibacterial activity of phosphanilic acid, alone and in combination with trimethoprim.

We explored the antibacterial activity of phosphanilic acid (P), an analog of sulfanilic acid, alone and in combination with trimethoprim (T; TP, 1:5) with sulfamethoxazole (S) and co-trimoxazole, the combination of this sulfonamide with trimethoprim (TS, 1:5) as the reference. P resembled S in spectrum but, in addition, had significant activity against Pseudomonas aeruginosa. The overall frequency and degree of synergism with TP were lower than with co-trimoxazole. P, like S, was strongly affected by changes in inoculum size and was not bactericidal. P was well absorbed parenterally but not orally in mice. Despite low (but prolonged) blood levels, P, given orally to mice, was effective in treating infections caused by P. aeruginosa. However, against most experimental infections the therapeutic effectiveness of P, as well as that of TP, administered either intramuscularly or orally was unimpressive. Based on in vivo data, the therapeutic application of P or TP would appear to be limited.

4-Aminobenzoic Acid

A murine model for listerial meningitis and meningoencephalomyelitis: therapeutic evaluation of drugs in mice.

Meningitis and meningoencephalomyelitis caused by Listeria monocytogenes were experimentally established in mice. The pathological changes in brain and spinal cord resulting from the infection resemble those observed in man and domestic animals. The efficacy of 24 antibiotics in treating this experimental infection was determined. Minocycline and chlortetracycline were the most efficacious antiotics followed by amoxicillin, which was 2- to 4-fold less active than the former. However, the acute toxicity of amoxicillin to the murine central nervous system was at least 10-fold lower than that of the tetracyclines. Since parenteral amoxicillin may be of value in the management of listerial meningitis and meningoencephalomyelitis in man and domestic animals, clinical trials seem warranted.

Animals

Bactericidal activity of cefadroxil, cephalexin, and cephradine in an in vitro pharmacokinetic model.

Cefadroxil (Duricef, Mead Johnson and Company), resembles cephalexin and cephradine in spectrum of antibacterial activity but differs in human pharmacokinetic properties. Whether the latter are likely to affect activity in vivo was assessed by determining bactericidal activity against clinical isolates under conditions simulating the variation of drug concentration in the blood stream after an oral dose of 500 mg to adults. In this kinetic model, cefadroxil was more active than cephalexin or cephradine against Staphylococcus aureus, Streptococcus pneumoniae, Klebsiella pneumoniae, Proteus mirabilis, Haemophilus influenzae and one of two strains of Escherichia coli. The other strain of E. coli was virtually unaffected by the cephalosporins. S. pyogenes was equally susceptible to all three cephalosporins. Analysis of the results suggest that the pharmocokinetic properties of an antibiotic affect its activity in the blood stream, provided the susceptibility of the infecting organism is concentration-dependent within the range of drug concentration occurring in serum.

Adult

Comparative bactericidal effect of ceforanide (BL-S 786) and five other cephalosporins in an in vitro pharmacokinetic model.

The bactericidal activity of ceforanide was compared, in an in vitro kinetic model, with that of five other cephalosproins: cephalothin, cefazolin, cefamandole, cefuroxime, and cefoxitin. Cultures of various pathogens in 95% human serum were incubated for 12 hours in the presence of the cephalosporins whose concentrations were modified periodically-by addition of a concentrated solution of drug or dilution with unmedicated serum-in order to simulate the variation of antibiotic concentration in human blood after one-gram intramuscular dose. One Gram-positive strain and six Gram-negative strains were used. Bactericidal activity was assessed by monitoring changes in the number of colony-forming units. Tests showed that against Klebsiella pneumoniae, ceforanide was the most active of the six cephalosporins. Proteus mirabilis was more susceptible to ceforanide and cefuroxime than to the other compounds; Enterobacter cloacae to ceforanide, cefuroxime, and cefamandole; Escherichia coli to ceforanide, cefuroxime, cefamandole, and cefazolin. The number of viable cells of Staphylococcus aureus was reduced below detectable levels by all cephalosporins except cefoxitin. On the other hand, Providencia stuartii was virtually unaffected by all of the cephalosporins except cefoxitin.

Bacteria

Laboratory evaluation of BL-S786, a cephalosporin with broad-spectrum antibacterial activity.

Biological and physicochemical properties of BL-S786 were compared with those of cephalothin, cephaloridine, and cefazolin. With few exceptions, BL-S786 was more active than the reference compounds against major gram-negative pathogenic species and its antibacterial spectrum was broader than that of cephalosporins currently available for clinical use. Although BL-S786 was generally less active than the control cephalosporins against gram-positive pathogens, it inhibited their growth at concentrations that should readily be achieved in humans after standard parenteral dosage. Streptococcus faecalis, a species relatively unsusceptible to cephalosporins in general, was an exception. BL-S786 was an effective bactericidal agent for strains of various gram-negative organisms. After intramuscular administration to mice, BL-S786 achieved high concentrations in blood, and its biological half-life was longer than that of the other three cephalosporins.

Animals

BL-S 640, a cephalosporin with a broad spectrum of antibacterial activity: properties in vitro.

BL-S 640 was evaluated in vitro by comparison with cephalothin, cephaloridine, cefazolin, and cephalexin. The new compound was more active than the control cephalosporins against most major gram-negative and some gram-positive species. Moreover, its antibacterial spectrum included strains of Enterobacter, Proteus morganii, P. rettgeri, and Providencia stuartii, species generally resistant to the other cephalosporins. BL-S 640 was an effective bactericidal agent for strains of various species of Enterobacteriaceae. In human plasma, the compound was 58% protein bound.

Bacteria

BL-S640, a cephalosporin with a broad spectrum of antibacterial activity: bioavailability and therapeutic properties in rodents.

The bioavailability and therapeutic properties of BL-S 640 in rodents were compared with those of cephalothin, cephaloridine, and cefazolin after parenteral administration, and cephalexin after oral administration. When given intramuscularly in dosages of 5 to 40 mg/kg, peak concentrations of BL-S 640 in the blood of mice were proportional to dose, but when given orally, they were proportional only up to a dose of 25 mg/kg. After either route of administration, the concentration of BL-S 640 in the blood declined at a slower rate than that of the control compounds. Rats receiving BL-S 640 orally excreted an average of 39% of the drug in the urine. BL-S 640 was highly effective in the treatment of mice infected systemically with a variety of pathogenic bacteria, its therapeutic efficacy in comparison with that of other cephalosporins being frequently in excess of what would have been predicted on the basis of comparative activities in vitro.

Animals