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Biomedical subjects

R Langer

Publications and source records attributed to R Langer.

At least 163 records · Page 9Linked to original sources
PubMed1997

Detection of radiographic findings in lung fibrosis using storage phosphor plates.

The aim of this work was to examine the influence of the filter kernel size on the detectability of differing radiological findings in interstitial lung disease. In 97 patients with confirmed pulmonary fibrosis chest radiographs were obtained with a filmscreen system of speed class 200 and with correspondingly exposed storage phosphorous plates. The size of the filter kernel used for the image postprocessing varied between sigma 5 and sigma 70. The detectability of interstitial lung changes was evaluated independently by eight readers on the basis of a defined rating system. The results were analysed using multifactorial analysis of variance with Scheffé test at a significance level of p = 0.05. Small kernel sizes (S 5, S 10) combined with high edge enhancement were only of benefit in the imaging of septal lines, but reduced the detectability of nodular and reticular structures. Good detail detectability of both micronodules and septal lines was obtained with a medium kernel size of sigma 40. Storage phosphor radiography utilizing the appropriate choice of postprocessing parameters provides equivalent image quality for evaluating interstitial lung changes compared with a modern filmscreen technique.

Female↗
PubMed1997

Computed tomography with iodine-free contrast media.

The purpose of this work was to evaluate the enhancement of different concentrations of gadolinium (Gd), ytterbium (Yb) and iodine in vitro and in vivo. Comparisons were made of the enhancement (HU) of Gd, Yb and iodine in concentrations ranging from 0.1 to 30 mg/ml. In vivo dynamic CT studies were performed in ten dogs with 0.5 M Gd, Yb and iodine. Time-density curves were achieved in aorta and liver. The in vitro studies confirmed a decrease in the enhancement in this order: Gd (120 kV) > Gd (137 kV) > Yb (120 kV) > Yb (137 kV) > iodine (120 kV) > iodine (137 kV). The specific enhancement of Gd was 40.8 (120 kV), of Yb 34.2 and of iodine 29.6 HU. The enhancement of the liver decreases from 21 HU (Gd) to 19 HU (Yb) and 12 HU (iodine). Gd and Yb achieved a higher aortal enhancement than iodine (190 vs 157 HU) All contrast media were well tolerated. Equimolar concentrations of Gd and Yb show a higher in vitro contrast and enhancement than iodine.

Animals↗
PubMed1997

The effect of donor and recipient age on engraftment of tissue-engineered liver.

A novel treatment for end-stage liver disease using heterotopic hepatocyte transplantation on biodegradable polymers has been investigated. Survival and repopulation of adequate cell mass to replace hepatic function has been the principal difficulty of this method. Hence the authors have begun to investigate the role of donor and recipient age on the efficiency of hepatocyte transplantation. Lewis rats were used as donors and recipients. Hepatocytes were isolated with a collagenase digestion, both for the adult and fetal livers (17 days estimated gestational age). After digestion, the hepatocytes were seeded onto 95% porous poly-(L)-lactic acid matrices. The polymer-cell constructs with adult or fetal cells were then implanted between mesenteric leaves of three different recipient groups: adults (approximately 200 g), 2-week, and 4-week neonates (two to five animals per group, depending on litter size). The specimens were harvested at 4 weeks, stained with Hematoxylin and Eosin (H&E), and the cell area of each specimen (24 sections per group) was quantitated using morphometric analysis. Results were statistically analyzed using an unpaired, two-tailed Student's t test. At 4 weeks, all specimens showed survival of groups of hepatocytes, especially along the periphery of the polymers and near blood vessels. The hepatocyte cell area for the six groups was calculated in square micrometers: the adult cells transplanted into adult recipients, 0.16 x 10(5) microns2; fetal cells into adults, 0.47 x 10(5) microns2; adult into 4-week neonates, 1.17 x 10(5) microns2; fetal into 4-week neonates, 4.54 x 10(5) microns2; adult into 2-week neonates, 2.98 x 10(5) microns2, and fetal into 2-week neonates, 5.81 x 10(5) microns2. In all three recipient groups, the area of fetal hepatocytes was approximately two to three times the area of the adult hepatocytes (P < .05 for 2-week and 4-week neonatal recipients, P = .06 for adult recipients). Also, as the recipient age decreased, there was an increase in the hepatocyte cell area (P < .05 for fetal or adult groups). The authors conclude that fetal hepatocytes heterotopically transplanted have a significant survival advantage over adult hepatocytes, independent of recipient age. The authors further conclude that the neonatal environment is more favorable than the adult environment for implantation of hepatocytes.

Age Factors↗
PubMed1997

Nanotechnology for biomaterials engineering: structural characterization of amphiphilic polymeric nanoparticles by 1H NMR spectroscopy.

Nanoparticles composed of diblock poly(D,L-lactide-co-glycolide)-poly(ethylene glycol) (PLGA-PEG) or a branched, multiblock PLA-(PEG)3 were prepared by the single emulsion technique. Results of previous studies of these nanoparticles suggested that their structure is of the core-corona type with a polyester core and an outer PEG coating. In the present study, 1H NMR spectroscopy was utilized to provide direct evidence of the structure of these nanoparticles suspended in an aqueous environment. The results confirm the existence of the core-corona structure under these conditions, and show that the PEG moieties extend out from the nanoparticle core into the aqueous environment, and exhibit chain mobility similar to that of PEG in solution.

Biocompatible Materials↗
PubMed1997

Controlled protein delivery from biodegradable tyrosine-containing poly(anhydride-co-imide) microspheres.

Polymer microspheres capable of the controlled release of macromolecules for periods ranging from days to over a month were developed. The microspheres were made using a new family of anhydride polymers: tyrosine-containing poly(anhydride-co-imides), specifically poly[trimellitylimido-L-tyrosine-co-sebacic acid-co-1,3-bis(carboxphenoxy)propane] anhydrides [poly(TMA-Tyr:SA:CPP)]. These polymers may be of particular interest for controlled delivery of vaccine antigens due to the incorporation of an immunological adjuvant, L-tyrosine, into their backbone. Microspheres were produced from a variety of polymer compositions using a double-emulsion solvent-evaporation technique, and tested for their ability to provide controlled release of a model protein, bovine serum albumin, in vitro. The microspheres are spherical with smooth surfaces and encapsulate greater than 70% of the protein. Protein release rates from polymers of identical composition could be varied from 0.3 to over 125 micrograms per mg spheres per month by changing the amount of protein encapsulated. This effect can be magnified by using polymers with various monomer ratios. A close correlation between protein release and polymer weight loss was observed, suggesting a release mechanism controlled mainly by polymer erosion. Bovine serum albumin release from poly(TMA-Tyr:SA:CPP) microspheres is also pH sensitive, being enhanced at high pH and depressed under acidic conditions.

Anhydrides↗
PubMed1997

Colorimetric analysis of surface reactive amino groups on poly(lactic acid-co-lysine):poly(lactic acid) blends.

The quantification of functional amino (NH2) groups on poly(lactic acid-co-lysine):(poly(L-lactic acid (PLAL:PLA) blends was performed using a colorimetric assay based on the reaction of sulpho-succinimidyl-4-O-(4,4'-dimethoxytrityl)-butyrate (sulpho-SDTB) with primary amino groups. The colorimetric assay was used to assess the available reactive sites for coupling of biologically active species to PLAL. Blends were created that contained from 10 to 70 wt% poly(lactic acid-co-lysine). Bulk lysine contents within the blends were determined by amino acid analysis and ranged from 9.1 micromol g(-1) to 52.9 micromol g(-1) for blends created using PLA of 100000g mol(-1) molecular weight. Surface amino group concentrations on the same set of blends ranged from 0.23 to 1.45 nmol cm(-2). Similar surface amino groups concentrations were measured on blends using 50000, 200000 and 300000g mol(-1) poly(lactic acid). Non-specific interactions of the colorimetric assay reagents with the PLAL-containing blends were measured on blends prepared from epsilon-amino protected PLAL and 100000g mol(-1) PLA. The presence of amino groups within the top 50 angstroms was confirmed by X-ray photoelectron spectroscopy.

Amino Acids↗
PubMed1997

Chronic local tissue reactions, long-term immunogenicity and immunologic priming of mice and guinea pigs to tetanus toxoid encapsulated in biodegradable polymer microspheres composed of poly lactide-co-glycolide polymers.

Immunogenicity of tetanus toxoid (TT) encapsulated in biodegradable polymer microspheres composed of poly lactide (PLA) or poly lactide-co-glycolide (PLGA) polymers was evaluated in mice and guinea pigs for 1 year. Microsphere formulations made from polymers differing in molecular weight and composition elicited significantly higher IgG antibody levels than soluble TT in mice. The antibody levels elicited by microsphere formulations in mice and guinea pigs were similar to those elicited by a single injection of AlPO4 adsorbed TT. Immunogenicity was not consistently better with a particular polymer composition, molecular weight or microsphere size. However, animals primed with TT-containing microspheres showed significantly higher anamnestic response to a low dose booster 1 year after priming than those primed with AlPO4 adsorbed TT. Microspheres made from low molecular weight PLGA polymer showed a minimal local tissue reaction 1 year after injection. In contrast, aluminum adjuvant formed local granulomas which persisted for 1 year after injection. Microsphere formulations used in this study released a small fraction of antigenic TT during in vitro release studies due to denaturation of TT during encapsulation and hydration of microspheres. Nevertheless, strong priming of immune responses were seen. It remains to be demonstrated whether stabilization of TT would lead to more immunogenic microsphere formulations.

Albumins↗
PubMed1997

The in vitro construction of a tissue engineered bioprosthetic heart valve.

PROBLEM: Heart valve replacement with either a nonliving xenograft or a mechanical prosthesis is an effective therapy for valvular heart disease. Both of these approaches have limitations, including their inability to grow, repair, and remodel. In addition, a mechanical prosthesis requires long-term anticoagulation therapy. METHODS: This study demonstrates the in vitro creation of tissue engineered heart valve tissue using cardiovascular cells on degradable polymer matrices, 40 heart valve leaflets were created using this technique from two sources. Xenograft leaflets were created using human dermal fibroblasts and bovine aortic endothelial cells (n = 20) or allograft valve leaflets were created using sheep myofibroblasts and sheep endothelial cells (n = 20). A mixed sheep cell population was obtained consisting of endothelial cells and myofibroblasts. Endothelial cells were labelled with acethylated low density lipoprotein (Ac-Dil-LDL) and cells were separated into two groups using an activated cell sorter: LDL positive cells comprised of a pure endothelial cell population and LDL negative cells comprised of mixed cell population containing myofibroblasts and smooth muscle cells. The LDL negative cells were seeded on a synthetic polyglycolic acid (PGA) mesh and grown in vitro to form a tissue-like fibroblast-mesh core. Endothelial cells were then seeded onto the surface of the fibroblast-mesh core, forming a single monolayer. RESULTS: Histological evaluation of these constructs revealed an inner core of LDL negative cells and outer endothelial-like cells which were factor VIII positive. There was no evidence of capillary formation from endothelial cells invading the myofibroblasts and smooth muscle matrix and the endothelial lining appeared complete. CONCLUSIONS: It is feasible to construct allogenic heart valve tissue which could be used to make a valve.

Animals↗
PubMed1997

Noninvasive in vivo monitoring of drug release and polymer erosion from biodegradable polymers by EPR spectroscopy and NMR imaging.

Biodegradable polymers have attracted much attention as implantable drug delivery systems. Uncertainty in extrapolating in vitro results to in vivo systems due to the difficulties of appropriate characterization in vivo, however, is a significant issue in the development of these systems. To circumvent this limitation, noninvasive magnetic resonance techniques, electron paramagnetic resonance (EPR) and magnetic resonance imaging (MRI), were applied to characterize drug release and polymer degradation in vitro and in vivo. MRI makes it possible to monitor water content, tablet shape, and response of the biological system such as edema and encapsulation. The results of the MRI experiments give the first direct proof in vivo of postulated mechanisms of polymer erosion. Using nitroxide radicals as model drug releasing compounds, information on the mechanism of drug release and microviscosity inside the implant can be obtained by means of 1.2 GHz EPR spectroscopy. To be able to attribute nitroxide mobility to a particular layer of the implant, sandwich-like tablets were manufactured, taking advantage of the distinct spectral features of nitroxides containing different isotopes of nitrogen (15N vs 14N). The use of both noninvasive methods to monitor processes in vivo leads to new insights in understanding the mechanisms of drug release and polymer degradation.

Biodegradation, Environmental↗
PubMed1997

Evaluation of solute permeation through the stratum corneum: lateral bilayer diffusion as the primary transport mechanism.

Solute permeation across human stratum corneum (SC) was examined in terms of the fundamental bilayer transport properties. A mathematical model was developed to describe the macroscopic SC permeation via the interkeratinocyte lipid domain in terms of (i) the structure and dimensions of the SC, and (ii) the microscale lipid bilayer transport properties, which include the bilayer/water partition coefficient, the lateral diffusion coefficient, the interfacial transbilayer mass transfer coefficient, and the intramembrane transbilayer mass transfer coefficient. The relative importance of the diffusive resistances associated with the bilayer transport properties was evaluated with the model and experimental data. Lateral diffusion coefficients in SC lipid bilayers were calculated from 120 human skin permeability measurements, and compared with previously reported measurements made in SC-extracted lipids. Good qualitative and quantitative agreement was observed, indicating that, in the context of the model, the diffusive resistance associated with lateral diffusion is sufficient to explain the overall resistance of solute permeation through the SC. A similar analysis shows that the diffusive resistance associated with interfacial transbilayer transport is not capable of explaining the experimental permeation values, thus supporting this finding. The lateral diffusion analysis also revealed a bifunctional size dependence of transport within the SC, with a strong size dependence for small solutes (<300 Da) and a weak size dependence for larger solutes.

Biological Transport↗
PubMed1997

A theoretical model of erosion and macromolecular drug release from biodegrading microspheres.

A theoretical model is outlined for predicting the time evolution of total mass, mean molecular weight, and drug release for the case of a spherical bulk-eroding microsphere, prepared by a double emulsification procedure and containing a hydrophilic drug, such as a protein or peptide. Explicit analytical formulae are derived for calculating the time evolution of measurable macroscopic characteristics, such as drug release or mean molecular weight. Microsphere hydration, polymer erosion, and drug release phases are each described. Results indicate that polymer degradation by only random-chain scission or only end scission (or unzipping) cannot explain experimentally observed kinetics of particle mass loss and molecular weight change; thus, a combined model (incorporating both random and end scission) is proposed. A general methodology for determining the microscopic transport coefficients (such as polymer degradation rate constant or drug diffusion coefficient) from erosion and release data is outlined. This paradigm is applied to the specific case of 50:50 poly(D,L-lactic-co-glycolic acid (PLGA) microspheres encapsulating glycoprotein 120 (gp 120), a candidate AIDS vaccine. Predictions permit comparisons with experimental data for mean weight- and number-averaged molecular weights, as well as for mass loss and protein release. Other comparisons are made with data appearing in the literature for release of tetanus toxoid from PLA and PLGA microspheres of variable molecular weight. Agreement between theory and experiment is observed.

AIDS Vaccines↗
PubMed1997

An explanation for the variation of the sonophoretic transdermal transport enhancement from drug to drug.

Over the last few decades, application of therapeutic ultrasound (frequency between 1 and 3 MHz and intensity between 1 and 2 W/cm2) has been attempted to enhance transdermal transport of several drugs, a method referred to as sonophoresis. The sonophoretic enhancement of transdermal drug transport was found to vary significantly from drug to drug. In certain cases, ultrasound did not induce any enhancement of transdermal drug transport. This variation in the efficacy of sonophoresis has raised a controversy regarding its applicability as a transdermal delivery enhancer. The objective of this paper is to provide a summary of the literature data on sonophoresis and an explanation for the observed variation of the sonophoretic enhancement from drug to drug. This paper also presents an equation to qualitatively predict whether therapeutic ultrasound may enhance transdermal transport of a given drug based on knowledge of the drug passive skin permeability and octanol-water partition coefficient.

Administration, Cutaneous↗
PubMed1997

[CT volumetry of the liver before transplantation].

PURPOSE: Purpose of the study was to assess the predictive accuracy of preoperative CT volumetry for water displacement volume after liver transplantation. METHODS: In a retrospective study the liver volume of 52 patients who underwent an orthotopic liver transplantation, was calculated preoperatively based on incremental and spiral computed tomography (CT). The calculated values were compared with the liver volume measured by water displacement and weight of the extirpated liver. RESULTS: Marked differences of 19-21.5% were seen between calculated CT volume and water displacement volume for the entire group, and of 12.4-16.9% for livers with a plausible physical liver density (0.9 and 1.1 g/cm3). In this group, 68-86% of the livers were in the acceptable tolerance range for a predictive accuracy (+10% to -20%). Other error sources, such as the breathing shift of the abdominal organs and interobserver variability (1.5-2.7%), were of minor importance for volume calculation. CONCLUSION: In conclusion, both incremental CT and spiral CT are reliable methods for the preoperative estimation of the liver volume, whereas best accordance with the corrected water displacement volume was obtained using the individual segmentation thresholds.

Adolescent↗
PubMed1997

Characterization of partially saturated poly(propylene fumarate) for orthopaedic application.

A partially saturated linear polyester based on poly(propylene fumarate) (PPF) was synthesized for potential application in filling skeletal defects. The synthesis was carried out according to a two-step reaction scheme. Propylene glycol and fumaryl chloride were first combined to form an intermediate fumaric diester. The intermediate was then subjected to a transesterification to form the PPF-based polymer. This method allowed for production of a polymer with a number average molecular weight up to 1500 and a polydispersity index of 2.8 and below. The polymeric backbone structure was investigated through the use of FTIR and NMR. Kinetic studies of the transesterification allowed mapping of the molecular weight increase with reaction time. The final product was also characterized by thermal and solubility analysis.

Bone Cements↗
PubMed1997

[Computerized tomography differentiation of hepatocellular carcinoma and cholangiocellular tumors].

20 patients with hepatocellular carcinomas (HCC) and 18 patients with tumours of the biliary passages and gallbladder (CAC)) were examined via angio-CT without table increment and via spiral CT. Evaluation of the time-density curve of angio-CT showed more rapid and greater enhancement in case of HCC, whereas CAC were characterised by slower and lesser contrast medium uptake than the surrounding hepatic tissue. Superior differential diagnostic information was obtained via angio-CT, whereas spiral CT yields the best information on extent and number of hepatic tumours.

Aged↗