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P Sanders

Publications and source records attributed to P Sanders.

At least 55 records · Page 3Linked to original sources
PubMed1997

Local control and survival in spinal cord compression from lymphoma and myeloma.

BACKGROUND: Between 1979 and 1989, 48 cases of extradural spinal cord and cauda equina compression in patients with lymphoma (24) and myeloma (24) received local radiation therapy for control of cord compression. Twenty five (52%) of the cases were treated by surgical decompression prior to irradiation. Thirty five (73%) of the cases received chemotherapy following the diagnosis of spinal cord compression. Post-treatment outcome was assessed at a minimum follow-up of 24 months to determine the significant clinical and treatment factors following irradiation. RESULTS: Seventeen (71%) of the lymphoma and 15 (63%) of the myeloma patients achieved local control, here defined as improvement to, or maintenance of ambulation with minimal or no assistance for 3 months from the start of radiotherapy. At a median follow-up of 30 (2-98) for the lymphoma and 10 (1-87) months for the myeloma patients, the results showed that survival following local radiation therapy for cord compression was independently influenced by the underlying disease type in favour of lymphoma compared to myeloma (P < 0.01). The median duration of local control and survival figures were 23 and 48 months for the lymphomas compared to 4.5 and 10 months for the myeloma cases. Survival was also independently influenced by preservation of sphincter function at initial presentation (P < 0.02) and the achievement of local control following treatment (P < 0.01). DISCUSSION: We conclude that while disease type independently impacts on outcome following treatment of spinal cord compression in lymphoma and myeloma, within both of these disease types the achievement of local control of spinal cord compression is an important management priority, for without local control survival may be adversely affected.

Adolescent↗
PubMed1997

Pharmacokinetics of flumequine in sheep after intravenous and intramuscular administration: bioavailability and tissue residue studies.

The pharmacokinetic properties of flumequine and its metabolite 7-hydroxyflumequine were determined in six healthy sheep after single intramuscular (i.m.) and intravenous (i.v) injections at a dose of 6 mg/kg body weight. The tissue residues were determined in 20 healthy sheep after repeated i.m. administration with a first dose of 12 mg/kg and nine doses of 6 mg/kg. The flumequine formulation used was Flumiquil 3% Suspension Injectable. The mean plasma concentrations of flumequine after i.v. administration were described by a three-compartment open model with a rapid distribution and a relatively slow elimination phase. The low value of volume of distribution at steady state (Vdss) (0.52 +/- 0.24 L/kg) and high value of volume of distribution (Vdlambda3) (5.05 +/- 3.47 L/kg) emphasized the existence of a small compartment with a slow rate of return to the central compartment. The mean elimination half-life was 11.5 h. The 7-hydroxyflumequine plasma levels represented 2.3% of the total area under the curve. The mean plasma concentrations of flumequine after i.m. administration were characteristic of a two-compartment model with a first order absorption. The mean maximal plasma concentration (1.83 +/- 1.15 microg/mL) was obtained rapidly, i.e. 1.39 +/- 0.71 h after the i.m. administration. The fraction of dose absorbed from the injection site was 85.00 +/- 30.13%. The minimal concentrations of flumequine during repeated treatment were significantly lower in females than in males. Eighteen hours after the last repeated i.m. administration, the highest concentration of flumequine was observed at the injection sites followed by kidney, liver, muscle and fat. The highest concentration of 7-hydroxyflumequine was observed in the kidney and was ten times lower than the flumequine concentration. The longest flumequine elimination half-life was observed in the fat.

Animals↗
PubMed1997

Addressing information security training and awareness within the European healthcare community.

This paper discusses the need to promote information security issues within modern healthcare establishments and the consequent need for appropriate training and awareness initiatives. Security is an area of extreme significance in healthcare information systems but, whilst the need is generally recognised, many personnel are not familiar with even basic concepts and procedures. As such, adequate promotion of security through training and awareness initiatives is viewed as a vital first step. The paper highlights a series of basic factors that healthcare establishments (HCEs) should consider in setting up a training and awareness framework. The discussion then examines a number of ways in which relevant information may be disseminated to staff, including security guidelines, training seminars and world-wide web based services. The paper is largely based upon work that is currently being conducted as part of the Health Telematics ISHTAR (Implementing Secure Healthcare Telematics Applications in euRope) project.

Awareness↗
PubMed1996

Pharmacokinetic-pharmacodynamic model for spiramycin in staphylococcal mastitis.

Simultaneous pharmacokinetic-pharmacodynamic (PK/PD) modelling for spiramycin in staphylococcal infections of the mammary gland of cows was used to predict the efficacy of spiramycin. A differential equation derived from the Zhi model was fitted to an in vitro killing curve and post-antibiotic effect determination. A seven-compartment PK model, in which 4 compartments representing each quarter of the mammary gland which was considered to be the effect compartment, was included. The PD model linked to the PK model was able to describe the in vivo spiramycin effect against Staphylococcus aureus. The parameters calculated from in vitro data predicted a rapid decrease for the first 12-24 h, and regrowth within 72 h following the treatment, whereas in vivo the bacterial effect was much less after 24 h than that predicted by the in vitro data. PK/PD modelling permitted the simulation of various doses to optimize the efficacy of the antibiotic, taking into account such dynamic parameters as bacterial growth rate constant, bacterial killing rate constant and the Michaelis-Menten type saturation constant. An optimal dosage regimen of 20000 IU/kg per day for 3 days was predicted for the treatment of Staphylococcus aureus mastitis.

Absorption↗
PubMed1996

[Bactericidal effect of colistin on Escherichia coli. Model and simulation or the pharmacokinetic-pharmacodynamic relation for prediction of efficacy in veterinary antibiotic therapy].

Pharmacodynamics studies consider three main parameters: the size of the bacterial population, the concentration of the antibiotic and the duration of its action. The pharmacodynamic characteristics of colistin were studied in vitro with Escherichia coli. The bacterial kinetics were fitted using differential equations. The mathematical model gave qualitative and quantitative information about the characteristics of the antibiotic-bacteria association. Above all, when linked to a pharmacokinetic model, the model permitted the prediction of the drug's efficiency. Simulations of various dosage levels in which the administration route, dose size, or interval between doses varied, permitted a more rational optimization than a prediction of efficacy based on the time taken to achieve antibiotic plasmatic concentrations above the minimal inhibitory concentration. Pharmacokinetic/pharmacodynamic modeling seems to be an interesting possibility for determining antibiotic dosing levels during the preclinical phase.

Animals↗
PubMed1996

[Bioavailability of muscle creatine kinase in sheep. Application to the assessment of local tolerance to injectable veterinary formulations].

Pharmacokinetic variables of skeletal muscle creatine kinase were determined in sheep after intravenous and intramuscular administration of the semipurified enzyme. Catheters implanted in the jugular vein were used for both intravenous injections and blood withdrawals. Blood sample collection by vacutainer and hemolysis may in fact have considerable effects on the measurement of creatine kinase activity in plasma. The change in the enzyme activity versus time in the plasma, after intravenous administration (123 +/- 38 U/kg) of creatine kinase, was fitted by a biexponential model. The mean volume of the central compartment (45 +/- 5 mL/kg) was approximately equal to the plasma volume. Plasma half-life and plasma clearance of creatine kinase were 3.7 +/- 1.7 h and 23 +/- 8 mL.kg-1.h-1, respectively. Mean plasma bioavailability of creatine kinase after intramuscular administration (357 +/- 36 U/kg) in both the loins and the gluteal mass was 42%. Maximal plasma activity was observed 4 and 5 h after injection and the half-life of the terminal phase was 7.3 or 8.6 h according to the muscle. The extent of muscle damage after intramuscular administrations of 21 veterinary drug formulations (one product per animal) was estimated from the total creatine kinase activity released in plasma during the 72 h following the injection. Equivalent weights of damaged muscle ranged from 1.4 to 83.3 g according to the irritant potency of the test formulation. Results differed only moderately between the injection sites (right and left gluteal mass) in the same animal. It can be concluded from this study that, in sheep: i) the bioavailability of creatine kinase from different injection sites (gluteal mass and loins) is comparable; and ii) the intra-individual variability in the estimation of muscle damage is moderate. Once validated, this non-invasive approach for local tolerance studies could be of value in assessing and comparing the irritant potency of veterinary drugs and in reducing the number of animals required.

Animals↗
PubMed1995

Mercy Healthcare's CARE 2000: an evolution in progress.

In a learning environment of shared governance, continuous quality improvement, and redesign principle application, disciplines of Mercy Healthcare San Diego produced their patient care delivery redesign model, Creative Actions Reflecting Excellence. Nurses, pharmacists, medical technologists, respiratory care practitioners, physicians, educators, managers, and many other professional and technical partners converted change and transition into opportunities. As disciplines understood and appreciated each other's unique and shared contributions, quality of care, stakeholder satisfaction, and process efficiencies increased.

Decision Making, Organizational↗
PubMed1994

Determination of spiramycin and neospiramycin in plasma and milk of lactating cows by reversed-phase high-performance liquid chromatography.

After chloroform extraction, the rapid and sensitive determination of spiramycin and neospiramycin can be performed with AASP-diol clean-up cartridges prior to reversed-phase C18 high-performance liquid chromatography. The limits of quantification of spiramycin in plasma and milk are 0.023 and 0.013 microgram/ml, respectively, and those of neospiramycin, are 0.058 and 0.006 microgram/ml, respectively. Application of the method to the analysis of plasma and milk samples obtained from pharmacokinetic studies is described. Spiramycin has a terminal half-life of 14.27 h in plasma and 34.59 h in milk, while neospiramycin has a half-life of 25.62 h in plasma and 105.85 h in milk.

Animals↗
PubMed1994

Confirmatory analysis for spiramycin residue in bovine muscle by liquid chromatography/particle beam mass spectrometry.

To ensure that residues of veterinary drugs, above their respective maximum residue limits, do not reach the human food supply, European Community regulations specify requirements for detection, quantification and confirmation analytical methods and control procedures. The European Community member states base meat controls on these protocols. A liquid chromatographic/mass spectrometric analysis of spiramycin in calf muscle is presented as a confirmatory method for this compound. A particle beam interface was used, with negative ion chemical ionization mass spectrometry, using methane as the reagent gas. Samples (2 g muscle were prepared by liquid/liquid extraction followed by solid-phase extraction clean-up. On-line liquid chromatography/mass spectrometry of extracts was carried out on a C-18 bonded silica column. The specificity required for a regulatory confirmation procedure was achieved by monitoring five fragment ions with m/z 304, 330, 475, 683 and 684. Variation of the relative ion abundances was less than 20% at the maximum limit of residue, 50 micrograms kg-1. The method specificity was tested for three related compounds: neospiramycin, erythromycin and tylosin. The detection limit based on ion chromatogram peaks areas obtained with control samples was determined to be 20 micrograms kg-1.

Animals↗
PubMed1994

Identification of tylosin in bovine muscle at the maximum residue limit level by liquid chromatography-mass spectrometry, using a particle beam interface.

A particle beam liquid chromatography-mass spectrometric method is presented as a confirmatory technique for analysis of tylosin residues in bovine muscle. After chloroform extraction and a diol solid-phase extraction clean-up, on-line liquid chromatography-mass spectrometry (LC-MS) of extracts is carried out on an RP-18 bonded silica column. The analyte is introduced into the ion source by a particle beam interface and identified by negative chemical ionization with selective ion monitoring. The tylosin molecular ion is obtained with this ionization mode. The response of the ion chromatogram peak areas is linear for the three levels of spiked muscle analysed (0.5, 1 and 2 maximum residue limit). Under these LC-MS conditions, other macrolide antibiotics such as spiramycin and erythromycin do not interfere with tylosin.

Animals↗
PubMed1994

Particle beam liquid chromatography-mass spectrometry method with negative ion chemical ionization for the confirmation of oxacillin, cloxacillin and dicloxacillin residues in bovine muscle.

To ensure human food safety, the European Union has defined maximum residue limits (MRLs) for veterinary drug residues in food products. Analytical methods need to be developed to confirm the presence of drugs at the MRL level. A method using particle beam liquid chromatography-mass spectrometry was developed for the confirmation of oxacillin, cloxacillin and dicloxacillin in bovine muscle at the maximum residue limit of 300 micrograms kg-1. Beta-lactams were extracted from tissues with ethyl acetate under slightly acidic conditions and separated on a C18 bonded silica column with a methanol-aqueous formic acid (2%) solution-acetonitrile mobile phase. Negative ion chemical ionization with methane as the reagent gas was used to identify the compounds. The specificity required for a regulatory confirmation procedure was achieved by monitoring five fragment ions for each compound (selected ion monitoring mode): m/z 183, 198, 213, 214 and 241 for oxacillin; m/z 196, 248, 250, 275 and 277 for cloxacillin; m/z 165, 230, 232, 274 and 276 for dicloxacillin.

Animals↗
PubMed1994

Pharmacokinetics and tissue residues of spiramycin in cattle after intramuscular administration of multiple doses.

Pharmacokinetic variables of spiramycin and its distribution in muscle, liver, kidney, and injection sites were studied in 18 mixed-sex 1-year-old calves to assess drug withdrawal time after 2 IM administrations of 100,000 IU of spiramycin/kg of body weight at 48-hour intervals. Presence of a compound, other than spiramycin I (ie, neospiramycin), was observed in tissues used for withdrawal time determination. High concentrations observed at the injection sites decreased slowly to maximal residue limit with half-life of 109.5 hours for neospiramycin and 77.5 hours for spiramycin. At 14 days, neospiramycin concentrations were higher in kidney than in liver and half-life was different between these 2 tissues. Two methods of withdrawal time determination were used and the part of the samples without residue detected, in the calculation, was discussed. Withdrawal time of 35 days can be proposed on the basis of average daily intake determined for spiramycin, with concentration at injection sites representing 10% of the whole muscle concentration.

Animals↗
PubMed1993

Regulation of tobacco acetolactate synthase gene expression.

Acetolactate synthase (ALS) catalyzes the first common step in the biosynthesis of isoleucine, leucine, and valine. The previous cloning of two tobacco (Nicotiana tabacum) ALS genes (SurA and SurB) has allowed transcript accumulation from these genes to be monitored. mRNA blot analysis of ALS transcripts showed a message size of 2.2 kb. Quantitation of the levels of ALS messages in tobacco organs indicated that there was 3- to 4-fold variation in the levels of expression of the ALS genes in different organs. This variability correlated with the developmental stage of the samples, with the highest levels of expression found in developing organs. In situ hybridizations of anti-mRNA probes to plant sections established that ALS messages are most prevalent in metabolically active and dividing cells of roots, stems, and floral tissue. Using RNase protection assays, the transcriptional start sites of the ALS genes were determined, and the expression levels of the two tobacco ALS genes were then followed separately. Both tobacco ALS genes are expressed in a coordinated manner in all tobacco organs examined, with the SurB gene being consistently expressed at higher levels than the SurA gene.

Acetolactate Synthase↗
PubMed1993

[Modeling of the bactericidal effect of spiramycin. Choice of a pharmacodynamic model].

The modelling of in vitro growth curves of Staphylococcus aureus ATCC 6538P at different pHs, of spiramycin killing curves and of the dose-effect relationship was performed. The growth curve was characterised by a Volterra-Kostitzin differential model, the main parameters of which were the bacterial growth rate constant of 0.95 +/- 0.13 h-1 and a lag-time of 0.74 +/- 0.36 h. The Zhi model used for bactericidal kinetics showed the same bacterial killing rate constant from a minimum concentration characteristic of "time-dependent" antibiotics. This differential model incorporated with pharmacokinetic models could lead to a rationale for proper dosage regimens.

Culture Media↗
PubMed1992

Determination of chloramphenicol in muscle using a particle beam interface for combining liquid chromatography with negative-ion chemical ionization mass spectrometry.

A simple and rapid liquid chromatographic-mass spectrometric analysis of chloramphenicol in calf muscle is presented. A particle beam interface was used, with negative-ion chemical ionization mass spectrometry using methane as the reagent gas. The method specificity was tested for three related compounds, dehydrochloramphenicol, nitrosochloramphenicol and nitrophenylaminopropanediol. The extraction procedures require 5 g of muscle, and the quantification limit is 2 micrograms/kg for chloramphenicol. Residues were detected in calf muscle 48 h after intravenous administration of chloramphenicol (25 mg/kg body weight).

Animals↗