bluuebunny/crossref_metadata_2025 huggingface dataset:
Analyte identification in capillary electrophoretic separation techniques
Authors: Kok Steven J. , Velthorst Nel H. , Gooijer Cees , Th. Brinkman Udo A.
Published: May 2005

A review on applications of on‐line hyphenation in capillary electrophoresis and capillary electrochromatography for the identification of migrating analytes is presented. There is an urgent need for unambiguous analyte identification by combining spectral information and observed migration times, because the parameters influencing the migration times and separation efficiencies in these separation techniques are not easily controlled, especially when real samples containing unknown interferences have to be analyzed. The spectrometric techniques covered here are ultraviolet and visible radiation (UV/Vis) absorption, fluorescence including fluorescence line‐narrowing spectroscopy, Raman spectroscopy, nuclear magnetic resonance and mass spectrometry. Attention is essentially confined to literature reports in which the extra information provided by the detector is really used for identification purposes, especially in real‐life samples, while the interfacing as such and analyte detectabilities in standard solutions are only briefly discussed. This article covers an extensive fraction of the literature published on this topic until the beginning of 1998.
Drug analysis by capillary electrophoresis and laser‐induced fluorescence
Authors: Couderc François , Caussé Elizabeth , Bayle Christophe
Published: May 2005

This review briefly presents the different laser‐induced fluorescence detectors, outlines the different dyes used to derivatize molecules which are used with capillary electrophoresis/laser‐induced fluorescence (CE‐LIF), and provides an overview and current status of CE‐LIF in drug analysis.
Separation of chiral compounds by capillary electrophoresis
Authors: Verleysen Katleen , Sandra Pat
Published: May 2005

This review presents the different chiral selectors used in capillary electrophoresis (CE) for the separation of enantiomers. The use of charged cyclodextrins, crown ethers, polysaccharides, proteins, natural and synthetic micelles, macrocyclic antibiotics and ergot alkaloids is discussed in detail. Neutral native and derivatized cyclodextrins are not treated because several review articles have already been published on this topic. Recent developments like the application of two chiral selectors in the same background electrolyte are highlighted.
Method development strategies for the enantioseparation of drugs by capillary electrophoresis using cyclodextrins as chiral additives
Authors: Fillet Marianne , Hubert Philippe , Crommen Jacques
Published: May 2005

General strategies for the development of capillary electrophoretic methods for the enantiomeric separation of basic, acidic or neutral drugs were developed. For all kinds of compounds, the use of a buffer made of 100 mM phosphoric acid adjusted to pH 3 with triethanolamine and containing anionic and/or uncharged cyclodextrin (CD) derivatives as chiral selectors was recommended. Two different optimization schemes depending on the acidic or basic character of the analytes, were elaborated. For most basic compounds present in cationic form at pH 3, enantiomeric separation could be achieved in the normal polarity mode. Different β‐cyclodextrin derivatives were first tested at a given concentration. Five derivatives were found to be particularly useful for enantioseparations in capillary electrophoresis (CE): the anionic carboxymethyl‐β‐CD (CMCD) and sulfobutyl‐β‐CD (SBCD) and the neutral dimethyl‐β‐CD (DMCD), trimethyl‐β‐CD (TMCD) and hydroxypropyl‐β‐CD (HPCD). After selection of the most suitable CD, its concentration was optimized with respect to chiral resolution. If necessary, a further improvement in resolution could often be obtained for the enantiomers of cationic solutes by increasing the buffer pH from 3 to 5 using CMCD as chiral additive. Another possible alternative for enhancement in chiral resolution was the addition of methanol or cyclohexanol to the buffer. For acidic drugs, essentially present in uncharged form at pH 3, and for neutral solutes, anionic CD derivatives such as SBCD or CMCD were first tested at a given concentration in the reversed polarity mode. Dual systems, based on the simultaneous addition of a charged CD (SBCD or CMCD) and a neutral CD (TMCD or DMCD), could then be investigated for resolution improvement. After optimization of the CD concentrations, the use of dual systems with CMCD at pH 5 could also be tested if necessary, especially for very weak acidic and neutral drugs. By applying these optimization strategies, 48 of the 50 drugs examined as model compounds could be fully enantioseparated by CE in short analysis times (usually less than 10 min).
Capillary electrophoresis for therapeutic drug monitoring
Authors: Brunner Lane J. , Dipiro Joseph T.
Published: May 2005

Therapeutic drug monitoring is commonly used in both the ambulatory and hospital patient care settings. Routine measurement of concentrations of therapeutic agents in biological fluids is critical for certain drugs to maintain therapeutic benefit with minimizing drug‐associated toxicities. Many analytical laboratory techniques are currently available to measure drug concentrations in biological samples. Recently there has been an increased interest in the use of capillary electrophoresis (CE) for measuring concentrations of therapeutic drugs in patient samples. However, while there are numerous reports of CE being used to measure drug concentrations in solution and pharmaceutical dosage forms, there are relatively few reports of the use of CE for measuring therapeutic agents in patient samples. The purpose of this paper is to provide an overview of methods currently used to measure therapeutic drugs in patient samples along with possible future trends for the use of CE in therapeutic drug monitoring.
Capillary electrophoresis for therapeutic drug monitoring of antiepileptics
Authors: Kataoka Yasufumi , Makino Kazutaka , Oishi Ryozo
Published: May 2005

We examined the use of capillary electrophoresis for therapeutic drug monitoring of antiepileptic drugs. Micellar electrokinetic capillary chromatography (MEKC) with a diode array detector simultaneously determined concentrations of zonisamide, a new type of antiepileptic drug, and phenobarbital, phenytoin and carbamazepine, typical antiepileptic drugs, in human serum. Zonisamide levels in human serum obtained by MEKC correlated well with levels obtained by high‐performance liquid chromatography. The serum levels of phenobarbital, phenytoin and carbamazepine determined by MEKC were almost equal to those obtained by fluorescence polarization immunoassay. The reproducibility of separation and quantification with MEKC for intra‐ and inter‐day assays were appropriate. This MEKC method could provide a simple and efficient therapeutic drug monitoring method for antiepileptic drugs, especially in patients treated with a combination of zonisamide and other antiepileptic drugs. MEKC may be an attractive method for therapeutic drug monitoring, because of its specificity of separation, automation of procedure, ease of method development, low cost, small aqueous buffer amounts, speed of analysis, small injection volume and high environment‐directed performance.
Characterization of partitioning behavior of cephalosporins using microemulsion and micellar electrokinetic chromatography
Authors: Mrestani Yahya , El‐Mokdad Nasr , Rüttinger Hans H. , Neubert Reinhard
Published: May 2005

Electrokinetic chromatography (EKC) was introduced to determine the partitioning behavior of various cephalosporins (cefpim, cefpirom, cefaloridin, cefaclor, cephalexin, cefuroxim, cefotaxim) in microemulsions (ME) and micellar (MC) systems. The partitioning behavior of cephalosporins in microemulsions was characterized calculating the capacity factor. The required parameters for the determination of the capacity factor (μaq and μme are the electrophoretic mobilities of the solutes in the aqueous phase and the microemulsion phase, μeff is the effective mobility in the microemulsion solution) were measured by EKC using cationic and anionic microemulsion systems consisting of the surfactants/n‐heptane/1‐butanol/10 mM phosphate buffer solution, pH 7.0. Electrokinetic chromatography was shown to be a useful method to quantify the partitioning behavior of drugs in oil/water microemulsion. The logarithm of the capacity factor was correlated with the logarithm of the 1‐octanol/water partitioning coefficients.
Effects of various anionic chiral selectors on the capillary electrophoresis separation of chiral phenethylamines and achiral neutral impurities present in illicit methamphetamine
Authors: Lurie Ira S. , Odeneal Norman G. , McKibben Timothy D. , Casale John F.
Published: May 2005

In this study, various anionic chiral selectors were investigated for the capillary electrophoresis (CE) separation of six chiral phenethylamines and three achiral neutral impurities which are commonly identified in illicit methamphetamine. Analyses were carried out at pH 8 (high osmotic flow) with untreated capillaries using 25 mMchiral surfactant or 10 mMcharged cyclodextrin. The chiral selectors included the micelle (R)‐N‐dodecoxycarbonylvaline (EnantioSelect (R)‐Val‐1)) (ES) and the cyclodextrins sulfobutyl(IV)‐ether‐β‐cyclodextrin (SBE(IV)‐β‐CD) (BSB4), SBE(VII)‐β‐CD (BSB7), SBE(XII)‐β‐CD (BSB12), SBE(IV)‐γ‐CD (GSB‐4), SBE(VII)‐γ‐CD (GSB‐7), sulfated(XI)‐α‐cyclodextrin (SU(XI)‐α‐CD (AS11), SU(VII)‐β‐CD (BS7), SU(XII)‐β‐CD (BS12) and SU(XIII)‐γ‐CD (GS13). Enantiomeric and achiral selectivity strongly depends on the size of the CD, the average degree of substitution, and the type of substitution. ES exhibits good performance for the neutral solutes, but exhibits enantiomeric selectivity only for the α‐hydroxyphenethylamines. GS13 provides the best overall enantiomeric selectivity. All fifteen solutes related to methamphetamine are simultaneously separated using BSB7.
Quality evaluation by capillary electrophoresis of amphotericin B injection after filtration through various membrane filters
Authors: Makino Kazutaka , Hirakawa Masaaki , Goto Yoko , Nakashima Kazue , Kataoka Yasufumi , Oishi Ryozo
Published: May 2005

The determination of amphotericin B, an antifungal agent, was developed using micellar electrokinetic capillary chromatography (MEKC) with a diode array detector. Repeatability and intermediate precision of MEKC analysis were acceptable. A high correlation was found between amphotericin B levels in pharmaceutical solutions obtained by MEKC and those by high‐performance liquid chromatography (HPLC) (r = 0.994). This MEKC method is therefore useful for the determination of amphotericin B. The concentration of amphotericin B did not significantly change after filtration through polyethersulfone (PES, 0.2 μm) and polyvinylidene difluoride (PVDF, 0.45 μm) membrane filters. When the Fungizone injection was filtered through PES (0.2 μm) and added to 5% dextrose for injection (500 mL), particulate matters larger than 10 μm decreased by 64% to a level under the standard defined by United States Pharmacopoeia (USP XXIII). PVDF filtration (0.45 μm) did not have this effect. Our results suggest that filtration of Fungizone injection through PES (0.2 μm) membrane filters is recommended for the preparation of intravenous amphotericin B fluid.
Therapeutic drug monitoring of doxorubicin in paediatric oncology using capillary electrophoresis
Authors: Hempel Georg , Schulze‐Westhoff Petra , Flege Silke , Laubrock Nora , Boos Joachim
Published: May 2005

A method for the determination of doxorubicin and its main metabolite doxorubicinol in human plasma is described. Two different sample preparation procedures are applied depending on the expected concentration: To monitor the peak plasma levels, 10 μL of plasma are deproteinated with acetonitrile. After centrifugation, the supernatant is directly applied to the capillary by hydrodynamic injection. For the determination of lower amounts of doxorubicin and its main metabolite doxorubicinol 100 μL of plasma is extracted by liquid‐/liquid extraction with chloroform. After evaporation of the organic phase, the sample is reconstituted in acetonitrile/water (95/5 v/v) and injected into the capillary by electrokinetic injection. Idarubicin serves as the internal standard. Laser‐induced fluorescence detection with an Ar‐ion laser emitting at 488 nm and a 520 nm cut‐off filter is used for detection. The accuracy of the method was calculated to be 3.0% at higher concentrations and 15.0% at the limit of quantification. Reproducibility data are in accordance to the generally accepted criteria for bioanalytical methods. The limit of quantification is 2 μg/L, enabling us to monitor doxorubicin plasma levels for several days after application. Noninvasive blood sampling (from the fingertip) using heparinized capillaries was found to be a simple and convenient procedure and provides reproducible data. Initial results show high interindividual variability in doxorubicin peak plasma levels.
Comparison of capillary electrophoresis‐based immunoassay with fluorescence polarization immunoassay for the immunodetermination of methamphetamine using various methamphetamine antibodies
Authors: Choi Jeongeun , Kim Choonmi , Choi Myung Ja
Published: May 2005

An accurate and simple immunoassay using capillary electrophoresis (CE) with laser‐induced fluorescence (LIF) was performed for the detection of methamphetamine (MA) in urine. The CE‐LIF was conducted with an untreated fused‐silica column using antiserum and a tracer of fluorescein isothiocyanate (FITC)‐labeled MA. This CE‐LIF system was compared with fluorescence polarization immunoassay (FPIA) in a TDx analyzer in the photo‐check mode using the same FITC‐labeled tracer and the same antiserum. Various antibodies, not only those prepared by our own immunogens but also those from commercial sources, were screened and characterized in both assay systems with regard to sensitivity, precision, and cross‐reactivity. Both systems satisfied analytical precision and gave similar cross‐reactivity patterns. However, the CE‐LIF‐based immunoassay was approximately one order superior to FPIA in sensitivity, requiring less volume of sample, antiserum, and tracer for the assay. Considering that the FPIA system is well known to be a useful tool for screening antibodies and detecting drugs, the CE‐LIF‐based immunoassay system, which is seemingly more advantageous than the FPIA system, appears to have great power for the characterization of antibodies and for the detection of MA in urine.
In vivo monitoring of gabapentin in rats: A microdialysis study coupled to capillary electrophoresis and laser‐induced fluorescence detection
Authors: Rada Pedro , Tucci Sonia , Pérez Jackeline , Teneud Luis , Chuecos Susana , Hernández Luis
Published: May 2005

Gabapentin (GP) is a new anticonvulsant used in refractory epilepsy. Few studies have monitored the drug in vivo. We report the combination of capillary electrophoresis and laser‐induced fluorescence detection (CZE‐LIFD) with brain microdialysis and plasma ultrafiltration in an attempt to measure GP and offer an alternative technique for pharmacokinetic studies. We found that CZE‐LIFD is capable of linearly measuring 10−7–10−9 M GP in a 1 nL volume. It was also demonstrated that it is possible to monitor GP in prefrontal cortex dialysates and plasma in rats. It is concluded that the method permits in vivo monitoring of the drug in pharmacological as well as in clinical studies.
Development of a simple high‐performance capillary electrophoretic method with on‐line mode in capillary derivatization for the determination of spermidine
Authors: Oguri Shigeyuki , Tsukamoto Asako , Yura Atuko , Miho Yamazaki
Published: May 2005

A new high‐performance capillary electrophoretic (HPCE) method with an on‐line mode in‐capillary derivatization (ICD) procedure for determinations of some amines using 20 mmol/L sodium dodecyl sulfate (SDS) ‐ 2 mmol/L o‐phthalaldehyde (OPA) ‐ 2 mmol/L N‐acetylcysteine (NAC) ‐ 20 mmol/L phosphate‐borate buffer [9] has previously been shown. Although this technique offers direct fluorescence detection of free amines without any derivatization procedures before or after HPCE separation, the presence of spermidine (Spd) is difficult to detect due to low fluorescence intensity. The purpose of this study is to improve the detection sensitivity of Spd by reoptimizing this method with regard to the run buffer; the reoptimized method was applied to the determination of Spd in human plasma. To enhance the fluorescence intensity of the Spd signal, it is effective to use the run buffer in the presence of both β‐cyclodextrin (β‐CD: 8.8 mmol/L) and NAC at high concentration (16 mmol/L). By contrast, the intensity was remarkably decreased when SDS was used in the presence of β‐CD. After ultrafiltrating (UF) spiked human plasma with Spd, UF plasma was directly analyzed using the reoptimized method. Spd peak was detected and separated from the other peaks of blank plasma. The present method gave good linearity (r = 0.999), reproducibility (3.85% coefficient of variation at 5 μmol/L level; n = 10) and specificity. The detection limit and lower limit of quantitation is for 0.2 μmol/L and 1 μmol/L, respectively.
Separation of etoposide phosphate and methotrexate by capillary zone electrophoresis using UV detection with a high sensitivity cell
Authors: Mrestani Yahya , Neubert Reinhard
Published: May 2005

Etoposide phosphate and methotrexate are important anti‐tumor chemotherapeutic agents. Our previously presented capillary zone electrophoresis (CZE) method using a high sensitivity cell (Z‐cell) for quantitative analysis in biological media (urine, plasma) showed good precision and accuracy. The present results show that the investigation using a capillary with high sensitivity cell led to an approximately 10‐fold improvement of the detection limit compared to standard capillaries. Plasma and urine samples were analyzed by using a calibration curve for drug concentrations between 0.1 and 100 μg/mL. Good detection limits and good relative standard deviations of the migration times and of the peak areas were observed in these experiments.
A simulation model of morphological, vegetation and sediment changes in ephemeral streams
Authors: Hooke J. M. , Brookes C. J. , Duane W. , Mant J. M.
Published: May 2005

A model to simulate channel changes in ephemeral river channels and to test the effects of hydrological changes due to climate change and[sol ]or land use change was developed under the auspices of the EU funded MEDALUS programme (Mediterranean Desertification and Land Use). The model, CHANGISM (Channel Change GIS Simulation Model), is designed to simulate the effect of channel flow events and of climate conditions on morphology, sediment and vegetation, through sequences of events and conditions, over periods of up to several decades. The modelling is based on cellular automata but with calculations for water and sediment continuity. Process rules have both deterministic and stochastic elements. An important feature of the model is that it incorporates feedback elements between each event. The main aim of the model is to indicate the likely outcomes of events and combinations of conditions. It is linked to GIS for both input and output. The modelling is based on a channel reach and state is input as GIS layers of morphology (DEM), sediment and vegetation cover and state. Other initial conditions of soil moisture, groundwater level, and overall gradient are input. Parameters for processes are read from tables and can be easily changed for successive runs of the model. The bases for decisions on process specifications are discussed in this paper. Initial tests of the operation and sensitivity of the model were made on idealized reaches. The model was then tested using data from monitored sites in SE Spain. Simulations using clearwater flow worked well but initial simulations using events with sediment loads showed some tendency for excess deposition. Further tests and modifications are taking place. Overall, the model is one of the most sophisticated that simulates the interaction of flows with sediment and vegetation and the outcomes in terms of erosion, deposition, morphology, sediment cover, vegetation cover and plant survival over periods of up to 30 years for the scale of a channel reach. Copyright © 2005 John Wiley & Sons, Ltd.
A simplified theory for generalizing results from a radiant panel rate of flame spread apparatus
Authors: Quintiere James
Published: May 2005

Experimental results on the rate of lateral flame spread and time for piloted ignition under an externally imposed radiant flux were analyzed with a simple theroretical model. The data were developed from a radiant panel apparatus that considers a wall mounted sample with a flux distribution \documentclass{article}\pagestyle{empty}\begin{document}$ (\dot q_{\rm e} ^{\prime \prime } ) $\end{document} of 5 W cm−2 at the ignited end to 0.2 W cm−2 at the other end. It is shown that after an appropriate preheating time (flux exposure time before sample is ignited) the rate of flame spread (Vf) results can be correlated by \documentclass{article}\pagestyle{empty}\begin{document}$ V_{\rm f} - {\textstyle{1 \over 2}} = C\left( {\dot q''_{{\rm o,ig}} - \dot q_{\rm e} ^{\prime \prime } } \right) $\end{document} where C is a material ‘constant’ and \documentclass{article}\pagestyle{empty}\begin{document}$ \dot q''{\rm }_{{\rm o,ig}} $\end{document} is minimum flux for piloted ignition—also a material (and configuration) constant. An extension of this model demonstrates that Vf can also be expressed in terms of an ‘ignition temperature’ and the surface temperature of the material. Both correlations are derivable from a single flame spread experiment. Results are presented for a number of typical wood and plastic materials.
The effect of chain extenders and stabilizers on the in‐vivo stability of polyurethanes
Authors: Hergenrother Robert W. , Wabers Hugh D. , Cooper Stuart L.
Published: May 2005

Poly(etherurethane) (PEU) and poly(etherurethaneurea) (Biomer®) films with and without antioxidant stabilizers were subcutaneously implanted into dogs and rats for up to 10 weeks. It was found that the molecular weight of the PEU films decreased over the 10‐week period, while the Biomer® films increased in molecular weight. The presence of the stabilizers resulted in less severe changes in molecular weight. Surface cracking was most pronounced on both the stabilized and nonstabilized PEU films. Stress did not have to be applied to induce the surface cracking.
Controlled release of bisphosphonate from a biodegradable implant: Evaluation of release kinetics and anticalcification effect
Authors: Golomb Gershon , Levi Matilda , Van Gelder Joel M.
Published: May 2005

The present investigation describes the formulation and the in vivo efficacy of prolonged controlled‐release chitosan matrices, containing the novel anticalcification agents adipoyland suberoylbisphosphonate (AdBP and SuBP). Chitosan matrices were prepared by the solvent‐cast method and the role of several factors such as polymer molecular weight (MW), crosslinking, and drug load concentration, on the release rate profile have been examined. Crosslinking of chitosan films retarded degradation rate of the polymer but not the release rate of the embedded drug. Chitosan's MW and drug load concentration did not affect drug release rate. The release kinetics of the bisacylphosphonates were characterized by initial burst‐effect and pseudo zero‐order kinetics in the following release phase. AdBP/chitosan matrices (co‐implanted subdermally in rats with the calcifiable bioprosthetic heart valve tissue) significantly inhibited tissue calcification after 15 and 30 days implantation (66.4 and 108.6 μg/mg Ca++ in comparison to 2.7 and 3.6 μg/mg Ca++, untreated and treated groups, respectively). No side effects were noted.
The effect of a thin coating of polymethylmethacrylate on the torsional fatigue strength of the cement‐metal interface
Authors: Davies Jeffrey P. , Singer Gordon , Harris William H.
Published: May 2005

Recent studies have established that a mechanism of initiation of failure of fixation of cemented femoral components is debonding of the cement‐metal interface. Other studies have shown that the torsional forces induced by stair climbing and rising from a chair are very high. Thus, the interface between the femoral prosthesis and the bone cement in total hip arthroplasty (THA) is required to transmit high torsional loads from the metal to the cement in a cyclic shear mode many times per year. These torsional loads likely contribute to the debonding. This study evaluated the efficacy of a thin layer of polymethylmethacrylate (PMMA) precoating in increasing the torsional fatigue strength of the cement‐metal interface. Fatigue studies were performed on 15 specimens. Each specimen was tested with and without PMMA precoating. The PMMA precoat significantly and substantially increased the torsional fatigue strength of the cement‐metal interface. Thus, PMMA precoating is likely to be a clinical advantage in maintaining the long‐term integrity of the cement‐prosthesis interface.
Histological techniques for the study of the biomaterial‐tissue interface of total joint replacements — a modification for the preservation of bone cement
Authors: Fornasier V. L. , Sanders G. , Goodman S. B.
Published: May 2005

The methods usually employed for the histological processing of orthopaedic specimens of cemented joint arthroplasties involve treatment with methacrylate monomer and organic solvents which dissolve the polymethylmethacrylate cement. This may distort the intimate relationship of the cell layers along the surface of the interface between the bone and the cemented implant. The authors report on a technique for the processing and embedding of cemented orthopaedic implants which permits preservation of the polymethylmethacrylate cement. The method utilizes a modification of Spurr's low viscosity epoxy resin and avoids the use of solvents such as acetone. Undecalcified sections of cemented joint replacements from animal studies and human specimens have been prepared using this method. It is possible to use these sections for detailed histomorphologic and histomorphometric analysis of bone tissue and of the soft tissue membrane adjacent to the polymethylmethacrylate cement.
Acute toxicity of metal ions in cultures of osteogenic cells derived from bone marrow stromal cells
Authors: Puleo David A. , Huh Winston W.
Published: May 2005

The effects of metal ions released from orthopedic implants on nearby bone cells remain largely unknown. The purpose of this study was to examine the acute toxicity of metal ions on osteogenic cells derived from bone marrow. Bone marrow stromalcells were cultured with metal ions found in commonly used orthopedic implants, that is, Ti‐6Al‐4V, Co‐Cr‐Mo, and 316L stainless steel. Solutions of individual ions and combinations representing the alloy composition were prepared from atomic absorption standards and added to the cultures to give concentrations ranging from 50 ppb to 5o ppm. After a 48‐h period of exposure to ions, the bone marrow cultures were examined for effects of cytotoxicity by measuring total cell number, total cell protein, and mitochondrial activity. Cr6+was grossly cytotoxic; Co2+, Mo6+, Fe3+, and Ni2+were moderately cytotoxic; and Ti4+, Al3+, V5+, and Mn2+were minimally toxic, as determined by the assays used. Ion solutions representing Co‐Cr‐Mo and 316L stainless steel were moderately toxic; solutions representing Ti‐6Al‐4V were toxic at only the highest concentrations used. The observed cytotoxicity was time‐dependent, with irreversible toxic effects being initiated following as short as a 3‐ to 6‐hour exposure. These results show that metal ions associated with Co‐Cr‐Mo and 316L stainless steel are toxic to osteogenic cells at concentrations approximating those measured in the fibrous membrane encapsulating orthopedic implants. © 1995 John Wiley & Sons, Inc.
Materials and design concepts for an intervertebral disc spacer. II. Multidurometer composite design
Authors: Vuono‐Hawkins Monica , Langrana Noshir A. , Parsons John R. , Lee Casey K. , Zimmerman Mark C.
Published: May 2005

The main function of the intervertebral disc is to transmit and attenuate compressive and torsional forces, and stabilize the intervertebral joint. Unfortunately, the disc may be displaced or damaged due to trauma or disease causing the nucleus to herniate and protrude into the vertebral canal or intervertebral foramen. Pressure on the spinal nerve may cause pain or paralysis in the area of its distribution. At present, the surgical procedures used to alleviate this condition include disc excision, and/or spinal fusion. A more desirable situation would involve removing the nucleus pulposus and part or all of the annulus fibrosis and implanting a suitable biofunctional equivalent. Such a prostheis should attenuate stresses and prevent abnormal stress at adjacent intervertebral joints. Maintenance of normal disc height would prevent impingement of the posterior facet joints and facet joint syndrome. In a previous companion paper (J. Applied Biomat. 5:125–132; 1994), the mechanical behavior of disc prostheses manufactured from fiber reinforced, elastomeric thermoset resins were examined. In order to develop devices which were more practical from a manufacturing standpoint and extremely reproducible, the fiber reinforced thermoset resins were replaced by multi‐durometer thermoplastic elastomeric materials. In the present paper, the mechanical properties of thermoplastic multicomponent desings have been investigated. © 1995 John Wiley & Sons, Inc.
Characterization of three formulations of a synthetic foam as models for a range of human cancellous bone types
Authors: Szivek John A. , Thompson Joel D. , Benjamin James B.
Published: May 2005

Porous polyurethane foams were prepared from Daro foam components with a range of mechanical properties to simulate human trabecular bone. Ratios of 10.0:5.0, 10.0:7.9, and 10.0:10.0 isocyanate to resin were mixed, cured, and cut into cubes. Properties were determined from uniaxial compression to 50% of the original cube height at a strain rate of 1.2 mm/s. Electron microscopy was used to characterize the foam structure. Average compressive yield stress values, ultimate compressive stresses, and elastic moduli ranged from 4.44 to 2.79, 5.61 to 3.28, and 134.0 to 110.1 MPa, respectively, for the three formulations. The foam materials showed a similar morphology of spherical bubbles, and the average bubble size tended to decrease as the ratio of isocyanate to resin increased even though the bubble size differences were not statistically significant. The results indicate that large blocks of foam can be prepared with consistent mechanical properties simulating a range of trabecular bone properties so that implants can be tested for various patient populations. © 1995 John Wiley & Sons, Inc.
Educational goals for biomaterials science and engineering: Prospective view
Authors: Von Recum Andreas F. , Laberge Martine
Published: May 2005

The research field of biomaterials and surgical implants has matured to a point suggesting that a formal and comprehensive education is now required to handle all professional issues related to biomaterials and implant development. A professional curriculum is proposed for a discipline of biomaterials science and engineering on a graduate level. The curriculum includes the definition of an essential knowledge base and describes two track options for a study period of 3 years. Lists of prerequisites as well as required and suggested courses are presented and discussed. Continuing education courses are presented as examples. A quick vision of the immediate future of the field enforces the need for biomaterials professionals to take the lead in bringing the field into the next century. © 1995 John Wiley & Sons, Inc.
Nucleation and mineralization of organic matrices
Authors: Walton A. G. , Friedman B. A. , Schwartz A.
Published: May 2005

Features controlling the initiation of matrix calcification have been investigated in a model system. Two major influences which dominate nucleation are the matrix integrity and the location of certain chemical binding sites. It has been shown that chemical chelating groups can, and do, promote calcification under simulated physiological conditions. Organically bound phosphate does not appear to promote nucleation, suggesting that it is chelation of calcium or other cations which is the initial step in tissue calcification. In the sequence of compounds investigated for nucleation catalysis, those possessing at least three chelating groups and a stereopsecific configuration were effective. The mineral phase forming first in association with the organic matrix is a soft non‐apatitic calcium phosphate of Ca/P ratio approximately 1.5. This is the same phase that forms in the absence of organic matrices at physiological pH and is probably the precursor to hydroxyapatite in biological calcification. It is suggested that nucleation catalysts exist both within and outside the collagen fibrillar framework. A possible location of the internal site has been proposed, based on the availability of a capillary channel and chelating ligands, and this postulate is supported by electron microscopic evidence which shows that bone crystals lie within the fibrils, occupying space which terminates in the polar 640 A staining area.
Effect of varying electrolyte concentration on in vitro streaming potentials across canine aortae and carotid arteries
Authors: Srinivasan S. , Burrowes C. B. , Lucas T. , Bauer S. B. , Sawyer P. N.
Published: May 2005

Knowledge of the characteristics of the blood–intima interface is important because it leads to information concerning (a) the normal antithrombotic mechanism (b) nature of interreactions between blood and intima (c) testing and selection of vascular wall substitutes which are antithrombotic and inhibit clotting. A technique for obtaining the electrical interfacial characteristics of blood vessel walls is by measuring streaming potentials. Experiments described in the present work are extensions of original in vivo streaming potential measurements. In vitro streaming potentials were measured across fresh canine aortae and carotid arteries using Krebs saline serum substitute, logarithmically varying both internal and external electrolyte concentrations. Positive streaming potentials were measured indicating that the blood vessel wall is negatively charged. Streaming potentials increased linearly with increasing flow rate, decreased with increasing internal electrolyte concentration, decreased with increasing external electrolyte concentration, and reversed, becoming positive, with aging of exteriorized artery. Thus the electrical characteristics of the blood vessel wall are dependent on an ionic balance between the blood vessel wall, flowing blood stream, and external environment. The information demonstrates the importance of electrochemical and physicochemical phenomena in the structure and function of the vascular interface and helps explain in vivo conditions conducive to or inhibitory of intravascular thrombosis.
Metallurgical analyses of failed orthopedic implants
Authors: Cahoon J. R. , Paxton H. W.
Published: May 2005

Several metallic orthopedic implants which failed in service and for which the medical histories are known are comprehensively examined using metallographic techniques and electron microprobe analyses to determine the causes of failure. The results indicate that fatigue is a major cause of failure and that, in all probability, the fatigue is initiated by poor design or poor material.
Utilization of polyelectrolyte complexes in biology and medicine
Authors: Markley Lita L. , Bixler Harris J. , Cross Robert A.
Published: May 2005

Polyelectrolyte complexes are ionic hydrogels formed by the coreaction of two oppositely charged, strongly ionized polyelectrolytes. While insoluble in simple solvents and infusible, these polymers can be fabricated into membranes, fibers, and other shaped articles by casting from ternary solvents. Homogeneous membranes are optically clear, amorphous structures in which the equilibrium gel water content can be controllably varied from ca. 30–90%. The net ion‐exchange capacity of the membrane can be varied from zero to ca. 2.0 meq/g, either cationic or anionic. Homogeneous membranes are characterized by unusually high water and gas permeabilities and permeabilities to water and soluble solutes which can be controlled by adjustment of gel water content and ion‐exchange capacity. Anisotropic membranes can also be prepared which are high flux molecular ultrafilters for solutes as small as sucrose. The anisotropic membranes have found widespread use in biology for fractionation, concentration, and purification of biopolymers. Homogeneous membranes show promise as analogues for biological membranes. A number of applications are being evaluated in medicine and surgery. These include: vascular grafts, antithrom‐bogenic coatings for plastic prostheses, contact lenses, corneal implants, and surgical adhesives. In addition, polyelectrolyte complex membranes are showing considerable promise for artificial kidneys and blood oxygenators.
Implant testing of polymerizing materials
Authors: Roydhouse Richard H.
Published: May 2005

An implant test, in which 0.3–0.5 g of solidifying or polymerizing material was injected into the belly wall of rats, was used to compare the tissue reactions to four materials. A histological survey was made of the tissue reactions to stainless steel pins, zinc oxide–eugenol mixtures, cold‐cure acrylic resin, silicate dental cement, and to a polymer–filler system (dental restorative). The irritant effects of the implant on the fibrous encapsulation about these foreign bodies were used to assess the toxicity of the material. Implanted stainless steel pins acted as a control for comparison. Zinc oxide–eugenol and silicate cement produced necrosis when injected in the mixed but unset state; the irritation continued for 30 days after implantation and was sufficient to impede fibrous encapsulation. Fibrous encapsulation about injections of cold cure acrylic resin and an experimental composite of polymer and filler occurred 5 days after similar encapsulation about implanted stainless steel implants. The inclusion of a relatively inert filler decreased the initial reaction to a monomer–catalyst mixture.
The determination of tear energy of extensible materials of dental interest
Authors: Webber Richard L. , Ryge Gunnar
Published: May 2005

The clinical performance of somatoprosthetic materials and some elastic impression materials has been related to their resistance to tearing. In most instances, the test method used has been tear strength determinations, many of which are notoriously sensitive to variations in specimen geometry. It has been shown that the energy per unit area of new torn surface is independent of specimen geometry. Two relatively simple equations were found to determine the probable range of energies involved in tearing standardized trouser‐shaped specimens regardless of the elastic properties of the materials tested. The energies so obtained for three highly extensible materials were found to be relatively independent of specimen geometry within the unstretched limits specified by ASTM test No. D 1938–62T. It is, therefore, concluded that a modification of Greensmith's trousers method for determining tear energy can be conveniently applied to extensible materials of dental interest.
Influence of acid‐treated Ag3Sn on the tensile strength and fracture of dental amalgam
Authors: Young F. A. , Wilsdorf H. G. F.
Published: May 2005

A dilute HCl wash of Ag3Sn powder results in a dental amalgam exhibiting 20% higher tensile strength. It was found that the fracture propagation paths in treated and untreated specimens were different.

The support of the National Institute of Dental Research under Grant No. DE‐30233 and Program Project DE‐02111 is gratefully acknowledged.
Antithrombogenic cellulose film
Authors: Britton R. A. , Merrill E. W. , Gilliand E. R. , Salzman E. W. , Austen W. G. , Kemp D. S.
Published: May 2005

A careful solvent‐exchange procedure followed by liquid‐phase reaction of ethyleneimine with cellulose film in a nonpolar solvent provides an effective method of uniformly aminoethylating cellulose. The protonated aminoethyl groups on the cellulose can then ionically bind heparin, a blood anticoagulant. Heparinized aminoethylated cellulose tubing at low levels of aminoethylation (ca. 0.2–0.3% nitrogen) exhibited excellent antithrombogenic properties as well as excellent mechanical strength properties. The in vitro tests demonstrated indefinitely long whole‐blood clotting times with normal thrombin times. In the in vivo experiments, the heparinized aminoethylated cellulose tubing provided extended patency when implanted intravascularly in the regions of low blood flow rate (infra renal inferior vena cava of dogs). A principal use of this film is in the artificial kidney.
Fiber metal composites in the fixation of skeletal prosthesis
Authors: Galante Jorge , Rostoker William
Published: May 2005

To serve as a component of a load‐bearing skeletal prosthesis, a porous material should offer the following attributes: (1) pore channels over 100μ in diameter; (2) continuity of pore channels; (3) matrix material inert and compatible with animal tissues; (4) manufacturable as thick coatings or thin‐walled complex surface assemblies; (5) manufacturable to precision dimensions; (6) large compliance comparable to bone; (7) crack resistance, particularly under impact.

A porous composite was manufactured by molding and sintering short metal fibers, which fulfilled all of these requirements. The composite was manufactured both with titanium and Vitallium fibers.

Experimental implants were performed in dogs and rabbits indicating peripheral bone formation around the implant at 2 weeks and penetration from 3 weeks on. Shear strength values at the prosthesis‐bone interface were in the range of 20 kg/cm2 3 weeks after implantation.

Femoral prostheses implanted in dogs revealed fixation by bone formation and maintenance by bone ingrowth up to 1 yr following implantation.

Massive incorporation with bone of skeletal segmental replacements for the baboon's femur were seen up to 3 months following implantation.

Practical problems that can be encountered with the use of porous fiber metal composites for prosthesis fixation relate to: (1) the possibility of long‐term corrosion occurring in an implant with a very large surface area; (2) technical problems with implantation requiring intimate contact between the fiber metal surface and the bone and (3) the difficulties in removing an implant which has failed for mechanical reasons requiring that a device manufactured using fiber metal composites for fixation be absolutely failure free from a mechanical viewpoint.
Biomechanical investigations of bone‐porous carbon and porous metal interfaces
Authors: Nilles J. L. , Lapitsky M.
Published: May 2005

The mechanical strengths of four types of ingrown porous carbon and two types of porous metal bone implants were correlated with the type of osseous ingrowth into the porous interfaces. Intracortical cylinders were implanted into canine long bones and examined at 3, 6, and 12 weeks. Histological techniques were used to study bone ingrowth. Tetracycline labelling and electron microprobe analysis were used to characterize the degree of mineralization of the ingrowth. Shear strengths of bone‐porous material interfaces were measured on cylinders forced out in compression. Histology revealed readily identifiable bone in most porous specimens. Mineralization was found to various depths in all porous specimens. After ingrowth, the porous metals, possessing appreciable inherent strength, displayed interfacial shear strengths from one‐third to two‐thirds that of cortical bone. The very porous carbon lattices, possessing little inherent strength, developed interfacial strength after ingrowth approaching that of the ingrowing cortical bone. The less open, more rigid porous carbon implants developed smaller interfacial strengths, averaging between one‐eighth and one‐half that of the ingrowing cortical bone.
Glassy carbon: A potential dental implant material
Authors: Hucke E. E. , Fuys R. A. , Craig R. G.
Published: May 2005

The carbonization of certain polymers under carefully controlled conditions yields glassy carbon bodies which may have potential application in the dental profession. Considerable evidence is now available for the good compatibility of a variety of carbonaceous materials with tissue and bone. Many carbons remain relatively inert in the human environment compared to metals and polymers. Disordered carbons with strengths exceeding that of graphite are commercially available with elastic modulus in the same range as that reported for bone(∼3 × 106 psi). The object of this study was to determine mechanical properties and characterize the structure of a new porous glassy carbon material.

Compressive and tensile strength data were obtained for carbon samples with a wide range of pore structures. A scanning electron microscope and a mercury porosimeter were used to observe variations in pore structures. The porous materials tested exhibited compressive strength values up to 48,000 psi and ultimate tensile strength values up to 7,500 psi. Sonic modulus values from 1 to 4.6 × 106 psi have been measured. Some carbon samples had interconnected porosity exceeding 50% and median pore diameters greater than 50 μ. Material with an interconnected mean pore size as small as 46 Å has also been produced. Preliminary animal implant studies are in progress.
Orthopedic implants—a clinical and metallurgical analysis
Authors: Weinstein A. , Amstutz H. , Pavon G. , Franceschini V.
Published: May 2005

A study of metallic implants consecutively removed from 133 patients at the Hospital for Special Surgery during a 2‐year period was conducted to evaluate their performance. They had been implanted for 2 weeks to over fifteen years. The implants studied consisted of prostheses and internal fixation devices used for open reduction of fractures or immobilization of osteotomies. The implants had been fabricated from either stainless steel or cobalt‐chromium alloys.

Case histories and roentgenograms were reviewed. A detailed inspection of each implant was performed including failure analysis when required. Crevice or fretting corrosion was noted on all but one stainless steel implant of the plate and screw type, and to a lesser extent with the cobalt‐chromium alloy implants. Extreme wear was noted on contact areas of articulating prosthetic components made of cobalt chromium alloy. Complete mechanical failures of internal fixation devices were attributable to fatigue, design deficiencies or misuse of the implant. These findings are discussed in light of the clinical results.
The measurement and effects of friction and wear in artificial hip joints
Authors: Walker P. S. , Salvati E.
Published: May 2005

The two systems for artificial hip joints in use at present are metal‐on‐metal and metal‐on‐plastic. There are many variables affecting friction and wear, which include diameter, sphericity, relative geometry of the components, and surface roughness. Tests in a simulating machine incorporated cyclic load and motion. Frictional torque of metal‐on‐plastic joints increased with diameter; Charnley 22 mm diameter producing lowest friction. For metal‐on‐metal the contact situation produced variable results, but friction was higher than for the plastic joints. Reciprocating friction machine tests suggested that high molecular weight polyethylene and AP4 polyester gave low friction and wear. Vitallium gave at least three times the friction of the plastic using γ‐globulin solution as lubricant; but wear appeared to be much less.