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In this critical reviewthe biocidal efficacies of a variety of antimicrobial coatings currently in use for catheter surfaces are discussed to formulate the best strategy for decreasing the risk of catheter-associated infections. The development of new coatings containing antimicrobial chemicals and light-activated antimicrobial agents, and their applicability for use in catheters are summarised (132 references). [ABSTRACT FROM AUTHOR]

We investigated bioadhesion (bacterial and cell adhesion) and biocompatibility of poly(tetrafluoroethylene-co-perfluoro-3,6-dioxa-4-methyl-7-octenesulfonic acid) (Nafion™) and compared the results with those obtained with poly(vinylidene fluoride-co-hexafluoropropylene) (PVFHFP). When incubated with bacteria for 4 h to 7 days, Nafion film exhibited scarce bacterial adhesion at 6 h, after which the adhesion gradually increasing to relatively low levels. In contrast, significant bacterial adhesion to PVFHFP film was observed at 4 h, and much higher adhesion levels were shown thereafter. Although HEp-2 human cells adhered normally to both films, reaching confluence in 7–8 days, the cells adhered to Nafion appeared more lively and stable than those to PVFHFP. Subcutaneous implantation in mice revealed that Nafion elicited a mild acute inflammatory reaction without chronic inflammation or tissue necrosis, indicating excellent biocompatibility in mice. PVFHFP, however, provoked a moderate and prolonged acute inflammatory response. These differences in the biological characteristics of Nafion and PVFHFP films may be attributable to the differences in the chemical and physical natures of these polymer films. Nafion film provided a sufficiently solid support, expressing a high surface charge density and good water-wettability. In summary, Nafion is suitable for use in biomedical applications that require biocompatibility with a reduced possibility of post-operative infections. [ABSTRACT FROM AUTHOR]

Health care associated infections and deaths have reached dimensions that rival traditional diseases and have become a serious financial burden on the health-care systems. Beyond simple hygiene, hopes are high that new materials capable of killing microorganisms on contact could ease the situation. This review highlights recent trends on surface-modifications capable of eliminating a microbial threat upon contact. Despite significant advances, the field still focuses on chemical synthesis and biological testing without breakthroughs in medical materials research. [ABSTRACT FROM AUTHOR]

The aim of this research was to examine whether a daily instillation of tetra sodium ethylenediaminetetraacetic acid (EDTA) solution could reduce the rate at which encrustation by crystalline Proteus mirabilis biofilms blocks urinary catheters. Sets of three bladder models were fitted with size 14 all-silicone catheters. Tetra sodium EDTA solution was instilled into the catheter following biofilm development. Catheters were examined by digital photography and scanning electron microscopy for evidence of encrustation. The results showed that the mean time to blockage of the control catheters was 45 h for saline, 57 h for water and 67 h for those exposed to daily instillations of the EDTA solution. Statistical analysis confirmed that the mean encrustation rate on the EDTA-treated catheters was significantly lower than on the control-treated devices ( P = 0.047). This in vitro study indicates that EDTA may have beneficial effects in reducing the complication of catheter encrustation and blockage by crystalline biofilms. [ABSTRACT FROM AUTHOR]

Adhesion of uropathogens to epithelial cells is considered as an indispensable prerequisite for the manifestation of urinary tract infections. This study was carried out to investigate the influence of urinary constituents, such as glucose, lactose, urea and creatinine either alone or in combination, on the adhesion of uroisolates of Pseudomonas aeruginosa (planktonic and biofilm cells) to uroepithelial cells (UECs). It was observed that with increase in concentrations of these urinary constituents there was increase in adhesion of both cell forms of P. aeruginosa to UECs. This was true for all the strains of P. aeruginosa. The results of the present study bring out that environmental conditions prevalent in the host milieu under different physiological and pathological conditions have the potential to alter the adhesion ability of P. aeruginosa which may play an important role in deciding the ultimate outcome of an infection. [ABSTRACT FROM AUTHOR]

Toluidine blue and toluidine blue-nanogold mixtures were incorporated into polyurethane and silicone polymers by a swell-encapsulation-shrink method using acetone-water mixtures. The surface and mechanical properties of the polymers were changed by the swell-shrink process especially the Young's modulus, but not by the introduction of toluidine blue or nanogold. The antibacterial properties of the various polymers were assessed under laser irradiation at 634 nm against Escherichia coliand methicillin-resistant Staphylococcus aureus(MRSA). The toluidine blue-incorporated polymers showed kills of (>105cfu/ml) for MRSA after just one minute of exposure. This is, to our knowledge, the most potent light-activated antimicrobial polymer combination reported to date. [ABSTRACT FROM AUTHOR]

The aim of this study was to examine the structure of the crystalline bacterial biofilms that encrust and block silver/hydrogel-coated latex catheters. Scanning electron microscopy was used to examine the crystalline deposits that were found encrusting catheters obtained from six patients undergoing long-term catheterization in a community setting. Large populations of bacilli and cocci were seen on all catheters developing on a basal foundation layer of crystalline material. These observations show that in patients prone to catheter encrustation, crystalline material formed in the urine can cover the surfaces of silver catheters. Extensive bacterial biofilms then develop on the crystals, shielded from the underlying silver. It is suggested that if antimicrobials are to be incorporated into catheters to prevent encrustation, they must diffuse out from the catheter surface and reduce the viable cell populations of the urease producing bacteria that elevate the urinary pH and trigger crystal formation. [ABSTRACT FROM AUTHOR]

Implant-associated infections can cause serious complications including osteomyelitis and soft tissue damage, and are a great problem due to the emergence of antibiotic resistant bacteria such as methicillin-resistant Staphylococcus aureus (MRSA). In some cases, antibiotic-loaded beads which release the antibiotic locally have been used, however such systems may lead to the development of antibiotic-resistant bacteria, as seen with gentamicin-loaded beads. Hence modifying the actual metal implant surface to inhibit or reduce initial bacterial adhesion may be an alternative option. This study describes the visualisation and quantification of S. aureus adhering to standard micro-rough ‘commercially pure’ titanium (TS) and Ti-6Al-7Nb (NS) surfaces, electropolished titanium (TE) and Ti-6Al-7Nb (NE) surfaces, and standard electropolished stainless steel (SS). Qualitative and quantitative results of S. aureus on the different surfaces correlated with each other, and showed significantly more live bacteria on NS than on the other surfaces, whilst there was no significant difference between the amount of bacteria on TS, TE, NE and SS surfaces. The results showed a significant decrease in the amount of bacteria adhering to the NE compared to standard NS surfaces. Such an observation suggests that the NS surface encouraged S. aureus adhesion, and could lead to higher infection rates in vivo. Hence electropolishing Ti-6Al-7Nb surfaces could be advantageous in osteosynthesis areas in minimising bacterial adhesion and lowering the rate of infection. [ABSTRACT FROM AUTHOR]

OBJECTIVES To test the ability of a sensor developed to signal infection by the organisms that generate the crystalline biofilms that encrust catheters, to give an early warning that encrustation was occurring on patients’ catheters, as the care of many patients undergoing long-term bladder catheterization is complicated by the encrustation and blockage of their catheters PATIENTS AND METHODS Twenty patients were followed prospectively for the lifetime of one of their catheters. Sensors based on cellulose acetate/bromothymol blue were placed in the urine-collection bags, which were changed as usual at weekly intervals. The bacteriology was assessed and pH determined weekly on urine samples. Photographic records were made of the sensors twice weekly. On removal, each catheter was examined for encrustation and blockage. RESULTS Proteus mirabilis was not isolated from five patients and in these cases the sensor colour remained golden-yellow to brown. The catheters drained for the scheduled period and showed no signs of encrustation. By contrast, the sensors turned dark blue/black in the urine of all 15 patients infected with P. mirabilis. All these patients’ catheters were encrusted and in 12 the catheters blocked. The mean interval between the sensor signalling and the catheter blocking was 12 days. CONCLUSION The cellulose acetate/bromothymol blue sensors placed in the urine collection bags are capable of signalling infection by P. mirabilis. They also signal the early stages of catheter encrustation and allow catheter replacement in ample time to avoid the clinical crises and emergency referrals caused by catheter blockage. [ABSTRACT FROM AUTHOR]

Biofilms are bacterial communities embedded in a glue-like matrix mostly composed of exopolysaccharides and a small amount of proteins and nucleic acids. Conventional disinfection and sterilization methods are often ineffective with the biofilms since microorganisms within the biofilm show different properties from those in free planktonic life. The use of the gas discharge plasmas is a novel alternative since the plasmas contain a mixture of charged particles, chemically reactive species, and UV radiation. The four-day-old single-species biofilms were produced using Chromobacterium violaceum, a gram-negative bacterium commonly present in soil and water. The gas discharge plasma was produced by using an Atomflo 250 reactor (Surfx Technologies), and the bacterial biofilms were exposed to it for different periods of time. Our results show that a 10-min plasma treatment is able to kill almost 100% of the cells. The results show a rapid initial decline in the colony forming units per milliliter (phase one) that is followed by a much slower subsequent decline (phase two) of the D-values that are longer than the inactivation of the planktonic organisms, suggesting a more complex inactivation mechanism for the biofilms. Two hypotheses are offered to explain this biphasic behavior. Optical emission spectroscopy was used to study the plasma composition, and the role of the active species is discussed. These results indicate the potential of plasma as an alternative way for biofilm removal. [ABSTRACT FROM AUTHOR]

Weekly urinalysis was conducted for 12 weeks on a group of 21 long-term catheter users with confirmed catheter encrustation and urinary tract colonization with urease-positive bacteria, in order to explore the cause of considerable variation in the severity of encrustation between sufferers. The rapidity of catheter blockage correlated significantly with the pH above which crystals precipitated from urine (the nucleation pH) but not the pH of the voided urine itself. Linear regression showed the nucleation pH to be significantly predicted by a combination of urinary calcium and magnesium concentrations, with calcium being the more influential variable. Reducing the rate of catheter encrustation could be achieved by lowering the urinary concentration of calcium and magnesium, which may only require catheter users to increase their fluid intake. [ABSTRACT FROM AUTHOR]

Traditional fecal coliform bacterial indicators have been found to be severely limited in determining the significance and sources of fecal contamination in ambient waters of tropical and subtropical regions. The bacteriophages that infect Bacteroides fragilis have been suggested as better fecal indicators and at least one type may be human specific. In this study, the phages that infect B. fragilis host RYC2056 (RYC), including phage B56-3, and host ATCC 51477-HSP40 (HSP), including the human specific phage B40-8, were evaluated in the drainage basins of Tampa Bay, 7 samples (n = 62), or 11%, tested positive for the presence of phages infecting the host HSP, whereas 28 samples, or 45%, tested positive using the host RYC. A survival study was also done to compare the persistence of phages B56-3 and B40-8 to MS2 coliphage in seawater at various temperatures. The decay rates for MS2 were 0.239 log10 d-1 at 10°C, but increased to 0.896 at 20°C and 2.62 log10 d-1 at 30°C. The two B. fragilis phages persisted much longer in the seawater compared to the coliphage and showed little variation between the temperatures. All sewage influents sampled from area wastewater treatment plants contained phages that infected the two B. fragilis hosts at levels from 1.2 × 104 to 1.11 × 105 pfu 100 ml-1 for host RYC and 67 to 350 pfu 100 ml-1 for host HSP. Of the 7 chlorinated effluent samples tested, 3 were positive for the presence of the phage using the host RYC and the phage enrichment method, with levels estimated to be <10 pfu 100 ml-1. No phages were detected using the host HSP in the treated sewage effluent. Coliphages were found in 3 of the 7 effluent samples at a range of 30 to 1.2 × 10³ pfu 100 ml-1. [ABSTRACT FROM AUTHOR]

The factors controlling the rate at which crystalline bacterial biofilms develop on indwelling bladder catheters are poorly understood. It is known that normally the pH of voided urine (pHv) is lower than the pH at which calcium and magnesium phosphates come out of urine solution (pHn). In patients who develop infections with urease producing bacteria, however, the pHv rises above the pHn and precipitation of the phosphates occurs in the urine and the biofilm. The aim of this study was to examine ways of manipulating the pHn of urine so that more of its calcium and magnesium remain in solution under alkaline conditions. The experimental data show that pHn can be elevated by decreasing the calcium, magnesium and phosphate concentrations. Increasing the fluid intake of a human subject so that the urinary calcium fell from 120 mg/l to 25 mg/l, for example, resulted in the pHn increasing from 6.48 to 8.22. The addition of citrate to urine also produced a rise in the pHn. The daily consumption of 500 ml of fresh orange juice increased urinary citrate concentrations from 0.35 to around 1.21 mg/ml and the pHn rose from 7.24 to 8.2. The pHn of urine is thus a highly variable parameter. It can be manipulated by controlling the urinary concentrations of magnesium, calcium, phosphate and citrate ions. We suggest that increasing fluid intake with citrate containing drinks would reduce the extent of encrustation on catheters in patients infected with urease producing bacteria. [ABSTRACT FROM AUTHOR]

To learn more whether toxin formation by cyanobacteria is controlled by quorum sensing, the concentrations of microcystins and of homoserine lactones have been followed during a summer period in the deep mesotrophic Lake Zürich and in the shallow eutrophic Lake Muzzano. Specific cyanobacterial populations are present in both lakes, Planktothrix rubescens dominates in Lake Zürich, Microcystis wesenbergii in Lake Muzzano. Both organisms produced microcystins, and homoserine-lactones were detected as well in most of the samples. However, no clear relation between the concentrations of the two compounds was observed with sampling intervals of 2 weeks. [ABSTRACT FROM AUTHOR]

Norfloxacin-releasing urethral catheters were prepared for the purpose of preventing urinary tract infections during long-term catheterization. The outer and inner surfaces of the catheters were coated with poly(ethylene-co-vinyl acetate) (EVA) and an amphiphilic multiblock co-polymer (PEO[sub 2k]PDMS), composed of poly(ethylene oxide) and poly(dimethyl siloxane). Norfloxacin, a fluoroquinolone synthetic antibiotic, was impregnated into a coating layer. The in vitro drug release behavior was monitored for 30 days, the surface topography was investigated using scanning electron microscopy (SEM) and the antibacterial activity against different bacteria implicated in urinary tract infection was evaluated by the in vitro inhibition zone test. All the coated catheters showed continuous delivery of norfloxacin for up to 30 days owing to hydrophobic natures of norfloxacin and EVA. PEO[sub 2k]PDMS incorporated in a coating layer produced a smooth and uniform surface. The coated catheters created considerable inhibition zones for 10 days against Escherichia coli, Klebsiella pneumoniae and Proteus vulgaris, indicating the continuous release of norfloxacin. Overall, it was evident that the catheters coated with EVA/PEO[sub 2k]PDMS blends containing norfloxacin have a promising potential for the clinical use in patients undergoing long-term catheterization. [ABSTRACT FROM AUTHOR]

Urethral catheters, widely used for the drainage of the bladder, are associated with most urinary tract infections (UTIs) that account for 40% of all episodes occurring in acute-care hospitals. This study aimed to develop a gentamicin-releasing catheter that effectively prevents UTIs for short-term catheterization. For physical loading of gentamicin, the urethral catheters were coated by the simple dipping method with poly(ethylene-co-vinyl acetate) (EVA) and EVA/poly(ethylene oxide) (PEO) blends containing gentamicin. By varying the molecular weight (MW) and contents of PEO in the blends, various catheter surfaces were produced. In vitro drug release studies demonstrated that all the coated catheters exhibited sustained release up to 7 days; however, the release pattern was significantly dependant on the coating layers. Of the coated catheters, EVA/PEO (MW = 100k)-coated catheters were utilized to evaluate the antibacterial activity using an inhibition zone test, since they showed a promising drug release behavior and had PEO-rich biocompatible surfaces. In accordance with drug release behavior, EVA/PEO-coated catheters exhibited antibacterial activities for 7 days against Proteus vulgaris, Staphylococcus aureus and Staphylococcus epidermidis. These results imply that the catheters coated with EVA/PEO have a potential for short-term catheterization. [ABSTRACT FROM AUTHOR]

PDMS-based polyurethanes (PUs) grafted with monomethoxy poly(ethylene glycol) (MPEG) were synthesized to develop a coating material for urinary catheters with a silicone surface for minimizing urinary tract infections. MPEG was grafted on PDMS-based PUs by two methods depending on the PU synthetic routes: esterification and allophanate reactions. It was confirmed from mechanical characterization that an increase of the hard segment amount enhanced the ultimate strength and Young's modulus, while reducing elongation at the end-points. The incorporation of MPEG in PDMS-based PUs induced a decrease in tensile strength and Young's modulus, and increased elongation at the break point due to its high flexibility. When hydrated in distilled water, mechanical properties of all PUs synthesized in this study deteriorated due to water absorption. It was evident from the bacterial adhesion test that PDMS-based PUs showed moderate resistance to adhesion of E. coli on their surfaces compared to Pellethane®, while the incorporation of MPEG significantly enhanced repellency to bacteria, including E. coli and S. epidermidis. We also studied the release behavior of an antibiotic drug, rifampicin, from the polymeric devices fabricated by solvent evaporation. Although rifampicin is hydrophilic and soluble in pH 7.4 phosphate buffer, it showed a sustained release over 45 days from PDMS-based PUs with MPEG that were grafted on ethylene glycol residues by allophanate reaction. This release characteristic was predominantly influenced by a hydrogen bond interaction between the polymers and rifampicin, which was confirmed through an ATR-IR study. This may imply that the specific interaction is responsible for the delayed release. Considering the mechanical properties, morphologies of drug-incorporated polymeric matrices, and drug release behaviors, PDMS-based PU with MPEG that were grafted on ethylene glycol (a chain extender) residues by allophanate reaction showed better material properties for uretharal catheter coating pusposes in order to minimize urinary tract infections. [ABSTRACT FROM AUTHOR]

A drug delivery system (DDS) which provides a sustained release of antibiotics at the focal site either singly, or in combination with a bone stimulating factor could both eliminate infection and increase the number of potentially healthy osteogenic cells. In this study, we address the use of a degradable gelatin DDS, for the combined release of therapeutic levels of both gentamicin and growth hormone (GH). An initial bolus release was observed during the first 24 h followed by a reduced, but sustained, release for both drugs up to 14 days. Bioactivity of gentamicin was demonstrated by growth inhibition of Staphylococcus aureus for over 96 h with a mean zone of inhibition of 29.4 mm (±0.19) for the time period studied. Furthermore, GH was shown to have a direct effect on primary human osteoblast-like (HOB) cells, stimulating proliferation and enhancing their differentiation. Site-specific drug delivery offers the advantage of localizing a drug directly at the target site, thus minimizing systemic effects. The results of this study suggest that gelatin is a good DDS for the combined release of drugs. In addition, gelatin is both biocompatible and biodegradable, thus making it a promising DDS for the management of acute and chronic bone and tissue infection such as osteomyelitis. © 1999 Kluwer Academic Publishers [ABSTRACT FROM AUTHOR]

The biofilm mode of growth has been implicated in the majority of human bacterial infections. In the urinary tract, notable biofilm-associated infections include prostatitis, chronic cystitis, struvite urolithiasis, and catheter-associated infections. Biofilms protect the causative organisms from host defences and antimicrobial therapy. Biofilm formation has traditionally been considered to result from adhesion and capsule formation by adherent microorganisms. Recent work has shown that a large number of genes are activated during this process, some of which have been associated with twitching motility, quorum sensing, and slow growth. In this paper, we review some of the recent work on biofilm biology and highlight its role in urinary tract infections, particularly those associated with urinary catheters. [ABSTRACT FROM AUTHOR]

Encrustation and blockage of indwelling urethral catheters is primarily brought about by infection of the urinary tract by Proteus mirabilis or other urease-producing species. The bacteria colonise the catheter forming a biofilm community within a polysaccharide matrix. The activity of the urease drives up the urinary pH and causes the crystallisation of calcium and magnesium phosphates in the biofilm. We have used a simple physical model of the catheterised bladder to investigate the ability of urease inhibitors to control encrustation. It was observed that acetohydroxamic acid (1.0 mg/ml) and fluorofamide (1.0 μg/ml) restricted the increase in pH of P. mirabilis-infected urine from 9.1 to 7.6. Significant reductions in the deposition of calcium and magnesium salts were also recorded on the silicone catheters. Electron microscopy confirmed that encrustation and occlusion of the catheter lumen was minimal in the presence of the urease inhibitors. The data from this in vitro study suggests that urease inhibitors, particularly fluorofamide, could have clinical applications in the prevention of catheter encrustation and blockage. [ABSTRACT FROM AUTHOR]

The activity of three antiseptic bladder washout solutions was examined in a physical model of the catheterized bladder. Tests were performed against cultures of four common urinary tract pathogens that had established themselves in the model and colonized the surfaces with biofilm. Double instillations of chlorhexidine (0.02% w/v) at 6-h intervals failed to eliminate Pseudomonas aeruginosa, Proteus mirabilis, and Providencia stuartii from the bladder model. Escherichia coli, however, was susceptible to a second instillation provided that it was performed within 12 h. Supplementing chlorhexidine with EDTA and TRIS potentiated its activity against E. coli. Mandelic acid (1.0% w/v) was the most effective of the agents, double instillations eliminating all but Pr. mirabilis infections. [ABSTRACT FROM AUTHOR]

The effects of chlorhexidine diacetate and benzalkonium chloride on the cell surface of a chlorhexidine-sensitive (Pv 2) and a chlorhexidine-resistant (Pv 67) strain of are described. Low concentrations of chlorhexidine diacetate (10 mg/l and upwards) increased the hydrophobicity of Pv 2, whilst having little effect on Pv 67. Both strains were resistant to benzalkonium chloride but a concentration as low as 2 mg/l induced a significant increase in hydrophobicity in Pv 2, with 25–50 mg/l needed to induce a similar type of increase in Pv 67. The possible nature of the resistance is discussed. [ABSTRACT FROM PUBLISHER]

- A simple physical model of the catheterised bladder has been used to assess the activities of antiseptic agents that have been recommended as bladder instillations in the treatment of urinary tract infections in patients with indwelling catheters. The activities of povidone-iodine, phenoxyethanol, chlorhexidine, chlorhexidine supplemented with EDTA+Tris, noxythiolin and neomycin were examined against selected species of uropathogens. Except for phenoxyethanol against Pv. stuartii and possibly Ps. aeruginosa, single applications of these antibacterials for 30 min were not effective in sterlising urine in the artificial bladder. However, a second application 1 h later of phenoxyethanol but not chlorhexidine or povidone-iodine did eradicate Ps. aeruginosa. It is suggested that bacteria growing as a film on the bladder wall are particularly resistant to antimicrobials. [ABSTRACT FROM AUTHOR]

The iron content of human nails has been measured by atomic absorption spectrophotometry and compared with other measurements of iron status including the bone marrow. Four groups of individuals were studied: 40 healthy laboratory staff, five iron-deficient subjects before and during iron therapy, four patients at various stages of treatment with iron, and 15 postmortem cases. The iron status of the individual was reflected by the amount of iron present in nail samples. Nail sampling is proposed as a cheap, noninvasive method of assessing the iron status of the individual. [ABSTRACT FROM PUBLISHER]

Characteristics of the T4 and T3 radioimmunoassay kits that are commercially available in the UK are described. Useful comparative data and criticism are given about many of these kits. Some unacceptable variation in accuracy is demonstrated. [ABSTRACT FROM PUBLISHER]

Seventy isolates of Providence were obtained from urinary tract infections in patients from five hospitals. They were all identified as Providence B (Providencia stuartii). A typing system was devised for these organisms based on their production of and sensitivity to bacteriophage and bacteriocins. Using this system, 27 distinct strains were recognized, and it was clear that many patients had been infected with the same strain. The minimum inhibitory concentrations of six antiseptics and disinfectants for these strains were determined. Many of the strains were up to 300-fold more resistant to the cationic antiseptics chlorhexidine, cetrimide, and Resiguard than the control strain Escherichia coli NCTC 10418. The sensitivities of the Providence strains to Hycolin, glutaraldehyde, and phenyl mercuric nitrate, however, were similar to those of the control organism. There were significant correlations between the sensitivities of the strains to the three cationic antiseptics. The loss of chlorhexidine resistance from a Providence strain after exposure of the cells to N-methyl-N' nitro N nitrosoguanidine resulted in a concomitant loss of resistance to cetrimide and Resiguard, but there was no significant increase in the sensitivity of the mutants to the other three antibacterials. [ABSTRACT FROM PUBLISHER]

A comparison has been made of the sensitivities to various antibiotic and non-antibiotic substances of some strains of and , the latter including strains isolated from eye and other cosmetic products and from other sources. Whereas strains showed a high resistance to cetrimide and to benzalkonium chloride, the strains were generally more sensitive to these and to chlorhexidine. The strains were also more sensitive to the various antibiotics tested. The loss of the ability to transfer an R factor by two strains of caused no significant change in their drug sensitivity pattern. [ABSTRACT FROM PUBLISHER]