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Combined low volume polyethylene glycol solution plus stimulant laxatives versus standard volume polyethylene glycol solution: a prospective, randomized study of colon cleansing before colonoscopy.

INTRODUCTION: The effectiveness of polyethylene glycol solutions (PEG) for colon cleansing is often limited by the inability of patients to drink adequate portions of the 4 L solution. The aim of the present study was to determine whether a reduced volume of PEG combined with stimulant laxatives would be better tolerated and as or more effective than the standard dose. METHODS: Patients undergoing outpatient colonoscopy were randomly assigned to receive either low-volume PEG plus sennosides (120 mg oral sennosides syrup followed by 2 L PEG) or the standard volume preparation (4 L PEG). The subjects rated the tolerability of the preparations and their symptoms. Colonoscopists were blind to the colonic cleansing preparation and graded the cleansing efficacy using a validated tool (the Ottawa scale). RESULTS: The low-volume PEG plus sennosides preparation was significantly better tolerated than the standard large volume PEG (P<0.001) but was less efficacious (P=0.03). Thirty-eight per cent of patients in the large volume PEG group were unable to finish the preparation, compared with only 6% in the reduced volume group. There were no adverse events reported. CONCLUSIONS: Although the low-volume PEG plus sennosides preparation was better tolerated, it was not as effective as standard large-volume PEG. However, in view of the significant difference in tolerance, further research investigating possible improvements in the reduced-volume regimen seems warranted.

Anthraquinones↗

Bone ingrowth in the presence of particulate polyethylene. Synergy between interface motion and particulate polyethylene in periprosthetic tissue response.

We have investigated whether the presence of polyethylene (PE) alone is sufficient to cause an aggressive periprosthetic tissue response, or whether certain mechanical interface conditions can allow bone to grow while in the presence of PE. An experimental implant was loaded in the presence and absence of particulate PE under stable and unstable conditions. Bone with a thin, discontinuous fibrous membrane formed in both groups of stable implants, either in the presence or absence of PE. By contrast, a continuous fibrous membrane consistently formed in both groups of unstable implants. The membrane consisted of loose fibrous connective tissue when PE was absent, and dense connective tissue with macrophages and a synovial lining when PE was present. In this model, if the interface was stable, the presence of PE was not sufficient to prevent the formation of bone or to produce a phagocytic tissue response. Only when the interface was unstable did a fibrous membrane form, and only then in the presence of PE.

Animals↗

Studies on the tumor-promoting activity of polyethylene: inhibitory activity of metabolic cooperation of polyethylene films containing an antioxidant.

Tumor-promoting activity, inhibitory activity on the gap-junctional intercellular communication of polyethylene (PE) film containing a model antioxidant, 2,2'-methylene-bis(4-methyl-6-tert-butylphenol) (MBMBP), at various amounts was assessed by V79 metabolic cooperation (MC) assay. The extracts prepared from PE film containing MBMBP showed the inhibitory activities and the potencies of the inhibitory activities depended on the amount of MBMBP involved in the film, whereas the extract prepared from MBMBP-free PE film did not show any inhibitory activities. However, the inhibitory activities were observed when MC assay was carried out on the surface of the MBMBP-free film. These findings indicate that tumor-promoting activity of PE film is influenced by the surface property of the film as well as by amount and kind of additives incorporated.

Antioxidants↗

Direct comparison of liposomal doxorubicin with or without polyethylene glycol coating in C-26 tumor-bearing mice: is surface coating with polyethylene glycol beneficial?

Sterically stabilized liposome is characterized by a surface coating of polyethylene glycol (PEG) or other polymers that can reduce opsonization of the liposome by plasma proteins. It has a higher plasma area under the concentration-time curve (AUC), which is believed to correlate with better therapeutic efficacy. However, the presence of large molecules on the liposomal surface may reduce the interactions of liposomes with cells and hinder entry of liposomes into the tumor tissue. Using a stable liposomal system composed of distearoyl phosphatidylcholine/cholesterol, we examined the effect of PEG (Mr 2000) on the pharmacokinetics and on the efficacy of liposomal doxorubicin with C-26 syngeneic tumor model in BALB/c mice. The plasma AUC of liposomal doxorubicin with 6 mol-% PEG-modified distearoyl phosphatidylethanolamine (PEG-DSPE) was approximately twice that of liposomal doxorubicin without PEG at various dosages, regardless of whether the mice were tumor-bearing. Paradoxically, the group of mice treated with liposomal doxorubicin without PEG had higher tumor doxorubicin concentrations. The 72-h tumor AUC was 1.44 times that of liposomal doxorubicin with 6% PEG-DSPE. The tumor-accumulation efficiency (AUC(Tumor)/AUC(Plasma)) of liposomal doxorubicin without PEG was 0.87, and this was more than twice that of the liposomal doxorubicin with 6% PEG-DSPE (0.31). At a dose of 10 mg/kg, although both liposomal groups were better than the free drug group in terms of clinically relevant parameters, including toxicity, tumor shrinkage, and survival, there was no difference between the two liposomal drug groups. In this stable liposome system, surface coating with PEG offered no benefit for liposomal doxorubicin in the C-26 tumor model. To enhance the therapeutic index of liposomal doxorubicin, simply increasing plasma AUC by surface coating with PEG may not be satisfactory.

Animals↗

Analysis of interfacial phenomena of aqueous solutions of polyethylene oxide and polyethylene glycol flowing in hydrophilic and hydrophobic capillary viscometers.

Viscosities of aqueous solutions of five polyethylene oxide (PEO) samples with molar masses from 1.5 x 10(5) to 1.0 x 10(6) were carefully measured in a polytetrafluoroethylene (PTFE) capillary Ubbelohde viscometer in the concentration range from dilute down to extremely dilute concentration regions and compared with those of the same sample obtained from a glass capillary viscometer. At the same time, viscosities of aqueous solutions of three PEG samples in glass and paraffin-coated capillary viscosity were measured. The wall effects occurred in viscosity measurements for PEO and PEG aqueous solutions in different capillary viscometers were theoretically analyzed and discussed. It was found that different interfacial behaviors occurred in both hydrophobic and hydrophilic capillary viscometers respectively and the interfacial behaviors also exhibit molar mass dependence.

Journal Article↗

Insight into the molecular arrangement of high-density polyethylene polymer chains in blends of polystyrene/highdensity polyethylene from differential scanning calorimetry and Raman techniques.

Polystyrene/high-density polyethylene (PS/HDPE) blends were synthesized by melt blending in a single screw extruder. Co-continuity measurements using solvent extraction and scanning electron (SEM) micrographs showed that co-continuity was obtained around 35% PS. Thermal analyses measurements revealed a reduction in crystallinity of the HDPE phase around the co-continuous composition. Raman analyses across the entire composition range of these blends showed an increase in the normalized integral intensities of the 1128 cm(-1) and 1061 cm(-1) stretching vibrations of the HDPE molecules. The presence of all-trans HDPE chains that are not packed into an orthorhombic structure is used to explain the simultaneous occurrence of reduced crystallinity and increased intensity of all-trans HDPE stretch vibrations.

Journal Article↗

Three-dimensional polyethylene wear of a press-fit titanium prosthesis. Factors influencing generation of polyethylene debris.

Between 1985 and 1990, 108 consecutive Harris-Galante I (Zimmer, Warsaw, IN) total hip arthroplasties were performed by four surgeons at a single hospital. At the time of follow-up evaluation, 80 hips were available for review. The mean rate of linear wear was 0.15 mm/y, mean rate of three-dimensional femoral head displacement was 0.21 mm/y, and mean rate of volumetric wear was 121 mm3/y. Eight hips (10%) in this series had radiologic osteolysis around either the femoral or acetabular component. A significantly greater volumetric wear rate was found in patients who were younger, those with a higher activity level, those who received a 32-mm-diameter femoral head, and those with vertical orientation of their acetabular component. No relationship could be made with patient weight, gender, Harris hip score, or cup diameter.

Adult↗

Accelerated clearance of polyethylene glycol-modified proteins by anti-polyethylene glycol IgM.

Tumor therapy by the preferential activation of a prodrug at tumor cells targeted with an antibody-enzyme conjugate may allow improved treatment efficacy with reduced side effects. We examined antibody-mediated clearance of poly(ethylene glycol)-modified beta-glucuronidase (betaG-sPEG) as a method to reduce serum concentrations of enzyme and minimize systemic prodrug activation. Enzyme-linked immunosorbent assay and immunoblot analysis of two monoclonal antibodies generated by immunization of BALB/c mice with an antibody-betaG-sPEG conjugate showed that mAb 1E8 (IgG1) bound betaG and betaG-sPEG whereas mAb AGP3 (IgM) bound poly(ethylene glycol). Neither antibody affected the betaG activity. mAb 1E8 and AGP3 were modified with 36 and 208 galactose residues (1E8-36G and AGP3-208G) with retention of 72 and 48% antigen-binding activity, respectively, to target immune complexes to the asialoglycoprotein receptor on liver cells. mAb 1E8 and AGP3 cleared betaG-PEG from the circulation of mice as effectively as 1E8-36G and AGP3-208G, respectively. mAb AGP3, however, cleared betaG-sPEG more completely and rapidly than 1E8, reducing the serum concentration of betaG-sPEG by 38-fold in 8 h. AGP3 also reduced the concentration of an antibody-betaG-sPEG conjugate in blood by 280-fold in 2 h and 940-fold in 24 h. AGP3-mediated clearance did not produce obvious damage to liver, spleen, or kidney tissues. In addition, AGP3 clearance of betaG-sPEG before administration of BHAMG, a glucuronide prodrug of p-hydroxyaniline mustard, prevented toxicity associated with systemic activation of the prodrug based on mouse weight and blood cell numbers. AGP3 should be generally useful for accelerating the clearance of PEG-modified proteins as well as for improving the tumor/blood ratios of antibody-betaG-PEG conjugates for glucuronide prodrug therapy of cancer.

Aniline Mustard↗

Blood plasma/implant interfaces FT--IR studies of adsorption on polyethylene and heparin-treated polyethylene surfaces.

Described is an attenuated total reflection (ATR), Fourier Transform infrared (FT--IR) technique useful for studying the adsorption of blood plasma proteins onto polymer surfaces. This technique had the advantage of employing whole blood plasma and has detected differences between the species adsorbed onto heparin-treated polymers as compared to the species adsorbed on untreated polymers. Differences detected consist of 1) changes in conformation and/or composition of proteins adsorbed on treated and untreated polymers, and 2) changes in amounts of carbohydrate-containing materials on the treated and untreated polymer surfaces. The advantages of FT-IR are its extreme sensitivity and its ability to work with highly complex systems such as whole blood plasma. These abilities should be of great value for providing direct molecular level information concerning protein adsorption from intact blood systems.

Adsorption↗