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Cytogenetic biomarkers, urinary metabolites and metabolic gene polymorphisms in workers exposed to styrene.

The present study comprised a biomonitoring study in 95 workers occupationally exposed to styrene and 98 unexposed controls, employing an integrated approach involving biomarkers of exposure, effect, and susceptibility. Airborne styrene was evaluated at workplace, and urinary styrene metabolites, mandelic acid (MA), phenylglyoxylic acid (PGA), vinylphenols (VPTs) and phenylhydroxyethylmercapturic acids (PHEMAs), were measured as biomarkers of internal dose. Cytogenetic alterations were evaluated by analysing the frequency of chromosomal aberrations (CAs) and micronucleated binucleated cells (MNBN) in peripheral blood lymphocytes. The micronucleus assay was coupled with centromeric fluorescence in situ hybridization to distinguish micronuclei (MN) arising from chromosomal breakage (C- MN) from those harboring whole chromosomes (C+ MN). The possible influence of genetic polymorphisms of xenobiotic-metabolizing enzymes involved in styrene biotransformation (EPHX1, GSTT1, GSTM1, GSTP1) and NAT2 on the cytogenetic endpoints was investigated. The exposed workers showed a significantly higher frequency of MNBN (13.8+/-0.5% versus 9.2+/-0.4%; P<0.001) compared to control subjects. The effect appeared to concern both C- and C+ MN. A positive correlation was seen between the frequency of C+ MN and urinary level of MA+PGA (P<0.05) and VPTs (P<0.001). Chromosome-type CAs positively correlated with airborne styrene level and VPTs (P<0.05), whereas chromatid-type CAs correlated with PHEMAs (P<0.05). Workers bearing GSTM1 null genotype showed lowered levels of PHEMAs (P<0.001). The GSTT1 null genotype was associated with increased MNBN frequencies in the exposed workers (P<0.05) and the fast activity EPHX genotype with a moderate decrease in both MNBN and CAs in the controls. Our results suggest that occupational exposure to styrene has genotoxic effects that are potentiated by the GSTT1 gene deletion. These observations may have relevance considering the risk of lymphatic and haematopoietic malignancies tentatively associated with styrene exposure.

Chromosome Aberrations↗

Ciprofloxacin interaction with silicon-based and conventional hydrogel contact lenses.

PURPOSE: Hydrogel contact lenses can be used as bandage lenses to protect the corneal surface after injury. The use of novel silicon-based hydrogel lens materials as bandage lenses has not gained widespread acceptance. As a first step toward advocating their usefulness as bandage lenses, their interaction with ocular pharmaceuticals must be understood because topical agents are often administered in conjunction with bandage lenses. METHODS: The in vitro uptake and release of ciprofloxacin from silicone-based hydrogel (SH) and conventional pHEMA-based (CH) hydrogel contact lenses was examined by spectrophotometric evaluation of the drug concentration in saline solution. RESULTS: The hydrogel contact lenses tested showed similar drug uptake (average 1800 microg/lens) but different levels of drug release. Multiphoton laser microscopy indicated that ciprofloxacin was distributed throughout the lens thickness, with higher levels of drug at the surface owing to drug precipitation. The drug adsorption onto the lenses was partially reversible. The SH lenses released a lower amount of drug than CH lenses (72 vs. 168 microg/lens). Ionic lenses released less drug than non-ionic lenses (127 vs. 151 microg/lens). CONCLUSIONS: The differences in ciprofloxacin uptake and release between SH and CH materials may not be clinically significant because the amount of drug released from all lenses would be above the MIC(90) of ciprofloxacin for common ocular pathogens. These results indicate that material properties have a significant impact on drug-lens interactions.

Adsorption↗

Biocompatibility of a nonpenetrating synthetic cornea in vascularized rabbit corneas.

PURPOSE: This study was designed to assess feasibility and biocompatibility of a lamellar, nonperforating supraDescemetic Synthetic Cornea (sDSC) implanted in rabbit eyes after a corneal injury. METHODS: Corneal vascularization and scarring was induced in the right eye of 15 rabbits by application of 1-heptanol and complete surgical removal of the limbus. An sDSC (7-mm diameter, 450-microm-thick optical zone, 100-microm-thick outer flange) was implanted after 45 +/- 5 days. The keratoprostheses were implanted with their central optic part positioned on a completely exposed Descemet's membrane (DM) while the outer flange was located in deep stroma. Three different materials were tested: hydrophobic PMMA (n = 5) and hydrophilic HEMA-MMA (n = 5) and HEMA-NVP (n = 5) with a water content of 34% and 75%, respectively. The corneal surface was covered with a conjunctiva-Tenon flap. Central flap trephination was performed after 63 +/- 7 days. DM vascularization and scarring was assessed and graded after flap opening and weekly thereafter. RESULTS: In all 15 consecutive cases implantation could be completed successfully without perforation of DM. Repair of the conjunctival flap had to be performed in five rabbits. Four months postoperatively, the flaps were opened. Four of five corneas (80%) with a PMMA implant and three of five (60%) with a HEMA-NVP75 implant had retained their original transparency. The others had developed significant neovascularization in the Descemet-sDSC optic interface. All corneas (100%) that received an sDSC made of HEMA-MMA34 displayed a completely clear DM without any vessels or scarring. DM was found firmly attached to the posterior surface of the optic. CONCLUSION: Implantation of a nonperforating synthetic cornea on top of an exposed DM is feasible. HEMA-MMA34 showed the most promising results. Because opening of the anterior chamber is not required, a lamellar supraDescemetic Synthetic Cornea would theoretically reduce some of the risks attributed to penetrating keratoprostheses.

Animals↗

AlphaCor: Clinical outcomes.

PURPOSE: To study the outcomes of AlphaCor implantation. METHODS: : The AlphaCor artificial cornea is indicated for corneal blindness not treatable by donor grafting. Prospective preoperative and follow-up data were collected. Data were evaluated using SPSS for statistical analysis of outcomes, trends, and associations. RESULTS: This report includes data returned through February 28, 2006, for all 322 devices implanted, with mean follow-up in situ of 15.5 months and a maximum of 7.4 years. The probability of AlphaCor retention at 6 months and 1 and 2 years for protocol cases was 92%, 80%, and 62%, respectively, and off-label cases were at higher risk (P = 0.010), as were cases not prescribed medroxyprogesterone (MPG; P = 0.001). Currently, the most common complications were stromal melting, fibrous reclosure of the posterior lamellar opening, and white intraoptic deposits, with incidences in 2005 of 11.4%, 5.1%, and 2.6%, respectively. MPG seems to protect against melts, and eyes with a history of herpetic keratitis were not at increased risk. A history of glaucoma or the presence of tubes did not affect device retention. Complications culminated in loss of an eye in 1.3%. Mean preoperative visual acuity (VA) was hand movements. The VA achieved postoperatively (light perception to 20/20) was affected by previous pathology and postoperative course, with a mean improvement of 2 lines. CONCLUSION: AlphaCor provides a treatment option where a donor tissue graft would not succeed in severe corneal conditions, while being reversible to a donor graft in the event of complications for anatomic integrity. Surgical technique and adjunctive therapies are evolving with experience. Continued data collection is important for a fuller understanding of AlphaCor's role.

Adult↗

Expanding MIRAgel scleral buckle simulating an orbital tumor in four cases.

PURPOSE: To describe four patients with an enlarging orbital mass from a swollen MIRAgel scleral buckle that simulated an orbital neoplasm. METHODS: In a retrospective, single-center case series at the Ocular Oncology Service at Wills Eye Hospital of Thomas Jefferson University, 4 eyes of 4 patients were referred for evaluation and treatment of a suspected orbital tumor. RESULTS: The initial presenting features were orbital mass (case 1), strabismus (case 2), and conjunctival mass with orbital extension (cases 3 and 4). Each patient vaguely recalled previous uncomplicated retinal detachment surgery 12 to 20 years earlier. Confirmation of the buckling implant material was made with the retina surgeon in 3 cases. A nontender, forniceal conjunctival mass, deep to the Tenon fascia and appearing as a translucent firm elevation was seen in all 4 cases. Axial CT (case 1) revealed a circumscribed anterior temporal orbital mass, believed to be a large inclusion cyst, 4 times thicker than the nasal scleral buckle. Ocular ultrasonography depicted an echolucent mass in the episcleral region (cases 3 and 4) that was 2 times thicker than the nasal scleral buckle (case 3). Excision was attempted in case 1, but only piecemeal removal was achieved, leading to extensive postoperative inflammation and decreased vision. The other 3 cases were followed conservatively without excision because they were each recognized to be a swollen MIRAgel implant and not an orbital tumor. CONCLUSIONS: MIRAgel scleral buckle material can greatly enlarge over a period of 10 years and simulate an orbital tumor or orbital cyst. Patients often do not recall details of the retinal surgery. Caution is advised regarding excision of this material because it is friable and can lead to extensive postoperative inflammation.

Adult↗

Restoration of enophthalmos in anophthalmic socket by HTR polymer.

A 2-year-old girl had undergone preoperative radiotherapy and enucleation without implantation for retinoblastoma in her right eye. She presented with supratarsal depression after secondary hydroxyapatite implantation. Computed tomography revealed insufficient right orbital volume, relative to left orbital volume. Injections of Bioplant hard tissue replacement synthetic bone filled the subperiosteal space of the orbital floor and lateral and medial wall for supratarsal augmentation. This had the desired effect: The filler lasted without sequela at least through 1.5 years of follow-up. Hard tissue replacement was also used to fill the remaining socket void and enhance the facial ridge width.

Biocompatible Materials↗

Tissue responses to Hydron, assessed by intraosseous implantation.

Teflon tubes containing freshly mixed, polymerized Hydron root canal filling material, fully set AH26 or Teflon were implanted into the mandible of guinea pigs and assessed histologically at 2 days, 1, 2, 4, 12 and 26 weeks. None of the materials tested elicited signs of overt or significant tissue damage, and polymerized Hydron was assessed to be as biocompatible as fully set AH26 and Teflon. Bone formed in very close apposition to the polymerized Hydron, whereas a soft tissue capsule separated the regenerated bone from implants of AH26 and Teflon.

Animals↗

Tissue responses to Hydron, assessed by intramuscular implantation.

Freshly mixed polymerized Hydron root canal filling material, fully set AH26 and Teflon were implanted in the quadriceps muscle of guinea pigs and assessed histologically at 2 days, 1, 2, 3, 12 and 26 weeks after implantation. All materials were characterized by peri-implant fibrous connective tissue capsule formation. Von Kossa-positive calcific material was observed at the implant-tissue interface of Hydron implants. The amount of apparently calcified material increased with time. Inflammation was not a prominent tissue response for any of the test materials, nor was a foreign body giant cell response.

Animals↗

Cell responses to Hydron by a new in-vitro method.

An in-vitro biotoxicity test system, suitable for the assessment of endodontic filling materials, has been developed and used to test cell responses to Hydron, AH26 and Tubliseal. A robust, well-characterized and stable cell line (L-cells) which was grown as uniform cultures on Millipore filters, has been used as indicator cells. As they approached confluence they were exposed to test substances for 24 h and biosynthetic activities were measured. The test system is a modification of that described by Wennberg et al. (1979). By inverting the cultures on organ-culture rafts, cells were separated from the test material, which was placed on top of the Millipore filters. Freshly mixed polymerizing Hydron and prepolymerized Hydron were tested. The cell responses were compared with those of cultures exposed to freshly mixed AH26 and Tubliseal. Polymerizing and prepolymerized Hydron depressed both cell division, assessed by 3H-thymidine incorporation, and the synthesis and secretion of matrix material as measured by precipitable 35S-sulphate. Prepolymerized Hydron decreased cell functions by 59% and 56% of live cell controls, respectively, while the freshly mixed polymerizing Hydron inhibited biosynthesis by 89% and 94%, respectively. The data for polymerizing Hydron were compared with results for other root-filling materials and showed similar values to those for Tubliseal (92% and 95%), but greater inhibition of biosynthesis than for AH26 (53% and 50%). The AH26 values were similar to those obtained from cultures exposed to the prepolymerized Hydron. Recovery of biosynthetic capacity by these cultures after removal of all endodontic material was also assessed. Partial biosynthetic recovery of cell cultures was observed 24 h after removal of preopolymerized Hydron.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

A five-year study of Hydron root canal fillings.

A prospective clinical and radiographic study was conducted in order to compare Hydron and laterally condensed gutta-percha/AH-26 root canal fillings. Paralleling technique periapical radiographs were taken preoperatively, postoperatively and at recall appointments at post-treatment intervals of 6 months, 1 year, 2 years, 3 years and 5 years. Clinical examination at the recall appointments revealed no adverse signs or symptoms amongst all the patients who attended (mean attendance 44.5% at each interval). Radiographs were scored according to the periapical status of the treated root, and comparable bone healing rates were observed between the two root-filling materials. Among the patients attending recall appointments, there were no radiographic signs of failure of any of the 39 gutta-percha/AH-26 root canal fillings. However, three of the 35 canals filled with Hydron were classified as failures, and four required further assessment after the 5-year recall appointment. This study indicated that Hydron and gutta-percha/AH-26 root canal fillings were well accepted but, on the basis of radiographic assessment, success with gutta-percha/AH-26 was more predictable.

Bismuth↗

Keratoprosthesis: preliminary results of an artificial corneal button as a full-thickness implant in the rabbit model.

PURPOSE: To develop a prototype artificial cornea and evaluate it in the rabbit model. METHODS: Hydrogel core-and-skirt keratoprostheses were made and were inserted as full-thickness implants covered with conjunctival flaps in the right eyes of eight rabbits. RESULTS: Peroperative complications related to inadequate mechanical strength led to failure in the early postoperative period in three animals, one was euthanased for an unrelated reason and the remaining four have been successful for up to 16 weeks' follow-up. CONCLUSIONS: Full-thickness implantation of an artificial cornea, analogous to penetrating keratoplasty, has been achieved in the rabbit model. Histological findings confirm that integration of the prosthesis with host tissue occurs. The main complications encountered in this preliminary series were related to inadequate strength of the sponge skirt of this prototype device. Work in our laboratories is now concentrated upon improving the mechanical qualities of the hydrogel skirt and on the enhancement of biointegration.

Animals↗

Human histologic evaluation of HTR polymer and freeze-dried bone allograft. A case report.

This case report compares the results of placement of HTR (Hard Tissue Replacement Synthetic Bone) and freeze-dried bone allograft (FDBA) in the same patient. 2 notches were made in each of 6 teeth, 1 at the gingival margin and the other at the most apical level of calculus. Soft tissue responses with both materials included probing depth reduction, gingival shrinkage and gain in clinical attachment. Histological sections of block extraction sites 30 months after placement of either material showed no signs of new attachment. Little or no inflammation was present with both materials. There was also an absence of all FDBA particles which assumes complete resorption of this material prior to 30 months. Gingival shrinkage resulted in the exposure of the gingival and calculus notch in all FDBA treated sites. Gingival epithelium was found adjacent to the gingival notch in all HTR treated sites. The calculus notch in HTR treated sites was lined by junctional epithelium with connective tissue and bone opposing the adhesion. HTR particles were present and surrounded by connective tissue or bone. HTR appears to serve as a scaffold for new bone formation when in close contact with alveolar bone.

Alveolar Bone Loss↗

A glove with exceptional protective features minimizes the risks of working with hazardous chemicals.

In continuation of our preceding studies, we disclose long-term experiments to test more extensively the protective power of the novel 4H Glove. 2 compounds encountered in modern electron microscopy technique, 1-hexadecene (1-HD) and 2-hydroxyethyl acrylate (2-HEA), which elicit allergic and/or toxic reactions in laboratory workers, were tested for their penetration through the 4H Glove material 1-HD has not to our knowledge been tested on any glove material. 2-HEA was known to have a breakthrough time exceeding 240 min; in contrast, it penetrates the common latex or vinyl gloves within minutes. When exposing the outside of a 4H Glove to 2-HEA for 200 h at 21 degrees C and then attaching the reverse unexposed side to a sensitized volunteer's forearm, 30 min of contact elicited a barely visible reddening of the skin at the contact site which disappeared within 24 h; 90 min of contact caused a somewhat stronger reddening limited to the contact area, which disappeared within 2 days. By the same criteria, 1-HD did not penetrate through the 4H Glove in 200 h. In an additional experiment, breakthrough time of 1-HD on latex gloves was less than 30 min.

Adult↗