Low temperature magnetic properties of Nd2Ru2O7.

We present magnetic susceptibility, heat capacity, and neutron diffraction measurements of polycrystalline Nd2Ru2O7 down to 0.4 K. Three anomalies in the magnetic susceptibility measurements at 146, 21 and 1.8 K are associated with an antiferromagnetic ordering of the Ru4+ moments, a weak ferromagnetic signal attributed to a canting of the Ru4+ and Nd3+ moments, and a long-range-ordering of the Nd3+ moments, respectively. The long-range order of the Nd3+ moments was observed in all the measurements, indicating that the ground state of the compound is not a spin glass. The magnetic entropy of Rln2 accumulated up to 5 K, suggests the Nd3+ has a doublet ground state. Lattice distortions accompany the transitions, as revealed by neutron diffraction measurements, and in agreement with earlier synchrotron x-ray studies. The magnetic moment of the Nd3+ ion at 0.4 K is estimated to be 1.54(2)µ B and the magnetic structure is all-in all-out as determined by our neutron diffraction measurements.

Complement-derived anaphylatoxins in human donor corneas treated with excimer laser.

BACKGROUND AND OBJECTIVE: An inflammatory response produced by excimer laser photorefractive keratectomy (PRK) may be associated with the subsequent corneal haze and regressions in refractive error observed after treatment. Complement-derived anaphylatoxins, potent mediators of inflammation, may have a role in postoperative healing. MATERIALS AND METHODS: Twenty right human donor corneas underwent a 6-D excimer laser PRK treatment. The corresponding left donor corneas served as the controls. After incubation in tissue culture media for 6 hours and elution in phosphate-buffered saline with EDTA for 24 hours, complement-derived anaphylatoxins C3a, C4a, and C5a were measured in corneal eluates by radioimmunoassay. RESULTS: Compared with control corneas, the excimer PRK corneas failed to demonstrate a significant increase in C3a, C4a, or C5a levels (P > .05). CONCLUSIONS: These results suggest that the excimer laser at this dose does not activate significant complement in the cornea.

Results of radial and astigmatic keratotomy by beginning refractive surgeons.

BACKGROUND: There is little information available on the results of radial and astigmatic keratotomy surgery that is performed by beginning refractive surgeons. METHODS: A retrospective review of all refractive keratotomies performed by Corneal Fellows in the University of California, Los Angeles, Department of Ophthalmology between October 1985 and October 1991 was performed. Data from all eyes with at least 3 months of follow-up were analyzed. Visual acuity, refractive error, and complication rates were compared with published case series. RESULTS: The mean preoperative spherical equivalent for the 79 eyes analyzed was -3.97 diopters (D) (range, -0.75 to -8.50 D). The mean postoperative spherical equivalent was -0.44 D (range, +1.50 to -3.88 D). The postoperative spherical equivalent was within 1.00 D of emmetropia in 85% of eyes, and uncorrected visual acuity was 20/40 or better in 94% of eyes. There were no vision-threatening complications. No patient lost more than one line of best-corrected visual acuity. CONCLUSION: Radial and astigmatic keratotomies that are performed by beginning refractive surgeons in a supervised setting can be safe and effective procedures with results comparable with those obtained by experienced refractive surgeons.

Ocular complications of systemic cancer chemotherapy.

Cancer chemotherapy has changed rapidly in recent years. New agents are constantly being developed. Established agents are being used with increased frequency, in new combinations, at higher dosages, and via new routes of administration. Enhanced survival, as well as increased drug toxicity, has resulted. Ocular toxicity is not uncommon and can greatly impact on quality of life. Practitioners in all fields are increasingly caring for patients who are receiving cancer chemotherapy. The recognition of eye disease resulting from chemotherapy is essential to appropriate patient management. We provide a review of the rapidly growing body of literature on the ocular toxicity of systemic cancer chemotherapy with particular attention to context, clinical course, mechanism, prevention and treatment.

An in vitro analysis of aminoglycoside corneal epithelial toxicity.

We evaluated the cytotoxicity of four aminoglycoside agents (neomycin, gentamicin, tobramycin, and amikacin) using an in vitro confluent rabbit corneal epithelial cell culture model. Primary corneal epithelial cell cultures were established and cells replated at 2 x 10(4) cells/2 cm2 well. After 48 hours either vehicle or an antibiotic was added at varying concentrations, each for 5, 30, or 60 minutes. 3H-thymidine was added immediately after drug removal and incorporation was measured 8 hours after drug or vehicle exposure. Comparisons of each drug to vehicle were expressed as % inhibition of control culture values. At the 5-minute exposure time tobramycin and amikacin showed no significant inhibition at any concentration, whereas neomycin and gentamicin showed significant inhibition at 6 mg/ml and 3.5 mg/ml or greater concentrations, respectively (p less than 0.05). At 30- and 60-minute exposure times all agents demonstrated significant inhibition at all tested concentrations in a non-dose dependent fashion (p less than 0.05). These in vitro data corroborate the animal and limited clinical data available for the aminoglycosides. Based on these toxicity profiles, tobramycin appears to be the topical agent of choice in the treatment of susceptible bacterial keratitis.

An in vitro method which assesses corneal epithelial toxicity due to antineoplastic, preservative and antimicrobial agents.

We developed an in vitro model for studying the cytotoxicity of pharmacologic agents on corneal epithelium employing 3H-thymidine incorporation. Primary rabbit corneal epithelial cell cultures were established, and the cells plated prior to each experiment. 3H-thymidine incorporation was measured after the addition of drug or vehicle to these confluent cells, and dose-response curves were generated. Marked inhibition of 3H-thymidine incorporation was reached at chemotherapeutic concentrations achieved clinically for cytosine arabinoside (10(-7) M), methotrexate (10(-3) M), and 5-fluorouracil (10(-6) M). A 10(-4) M concentration of 2-deoxycytidine, a naturally occurring competitive inhibitor of cytosine arabinoside, protected cells up to a concentration of 10(-5) M. We utilized these data to undertake an in vivo prophylaxis study in 13 leukemia patients receiving high-dose iv cytosine arabinoside. Topical deoxycytidine 10(-4) M and 1% prednisolone phosphate, given 12 hours prior to the start of antileukemic therapy, were effective in reducing symptoms and signs of keratitis; both were better than historical placebo-treated eyes. Ophthalmic preservatives were studied in vitro at concentrations used clinically: benzalkonium chloride (BAC) (0.004-0.02%) was the most toxic, thimerosal (TMS) (0.001-0.004%) intermediate, and chlorobutanol (CHB) (0.2-0.5%) the least toxic. Antiviral agents (final concentration) included: trifluridine (TFT) (1.0%), ethyldeoxuridine (EDU) (2.0%), and idoxuridine (IDU) (0.1%). Dose but not time-dependent concentrations of these 3 agents were noted to cause toxicity; however, (E)-5(2-bromovinyl)-2'-deoxyuridine (BVDU) (0.1%) was non-toxic. Similarly, tobramycin and amikacin were significantly less toxic than gentamicin and neomycin in this system. These in vitro cytotoxicity data correlate well with previous in vivo and pre-clinical corneal epithelial toxicity studies. Our model may be useful in the toxicologic study of future topical ophthalmic agents.

An in vitro study of ophthalmic antiviral agent toxicity on rabbit corneal epithelium.

Using an in vitro system we measured the corneal epithelial cytotoxicity and the antiviral activity of the antiviral agents idoxuridine (IDU), trifluridine (TFT), ethyldeoxyuridine (EDU), and (E)-5-(2-Bromovinyl)-2'-deoxyuridine (BVDU). Confluent rabbit corneal epithelial cell cultures were established, and the antiviral agents were added for 5, 30, or 60 min at a range of concentrations including that used clinically (IDU 0.1%, TFT 1.0%, BVDU 0.1%, EDU 2.0%). Twelve hour [3H]thymidine incorporation then was measured and expressed as % inhibition of control cultures. In separate experiments confluent corneal epithelial cell monolayers were inoculated with 10(4) plaque forming units (PFU) of HSV type 1 (McKrae strain) for 1 h, and IDU 0.1%, TFT 1.0%, and BVDU 0.1% were added to the culture for determination of PFU inhibition. Significant dose-, but not time-dependent, toxicity was observed at the clinical concentrations of IDU, TFT, and EDU. Toxicity was absent for BVDU. TFT and IDU were the most toxic, and EDU was of intermediate toxicity. IDU, TFT, and BVDU showed significant antiviral activity in this corneal epithelial cell culture system (TFT greater than BVDU greater than IDU). The results of this in vitro study paralleled the findings of previous in vivo corneal epithelial toxicity studies of IDU, TFT, and BVDU. Our data, however, suggest that EDU has a potential for clinical toxicity and further studies are recommended. Our model may be useful in the future toxicologic study of new antiviral agents.

Mechanism of inhibition of granulopoiesis by ethanol.

The mechanism of inhibition of neutrophilic granulopoiesis by ethanol has not been well characterized. Possible mechanisms investigated include: (a) a direct toxic effect on the granulocyte-macrophage cluster-colony forming unit (CFU-GM), and/or (b) inhibition of production of CFU-GM proliferation stimulating factor activity (CSA) from T lymphocytes (T cells). Addition of as much as 600 mg% ethanol to T-cell- and monocyte-depleted light-density marrow (TMoDLDBM) cells from humans in soft agar cultures which were stimulated with an exogenous source of CSA did not inhibit the CFU-GM proliferation, suggesting that ethanol has no direct toxic effect on the CFU-GM. T cells obtained from the blood of normal humans were cultured in the presence of phytohemagglutinin with 100 to 600 mg% ethanol. Cell-free conditioned media (CM) from these cultures were tested for CSA concentration by their capacity to stimulate proliferation of CFU-GM from human TMoDLDBM or rat whole bone marrow cells. The results indicated that ethanol at a concentration greater than 100 mg% inhibited CSA production from T cells. There was no evidence for production of an inhibitor of CFU-GM proliferation from T cells in the presence of ethanol. These results suggest that the neutropenia which occurs in relation to alcohol abuse may in part be related to decreased CSA production from T cells.