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Combination of oral terbinafine and topical ciclopirox compared to oral terbinafine for the treatment of onychomycosis.

BACKGROUND: Treatment of onychomycosis has recently been enhanced by the introduction of combination therapies. OBJECTIVE: To evaluate the efficacy of a combination therapy of ciclopirox nail lacquer and oral terbinafine compared to oral terbinafine monotherapy for the treatment of onychomycosis caused by dermatophytes. PATIENTS AND METHODS: Eighty patients with onychomycosis were randomly assigned to receive either oral terbinafine 250 mg/day for 16 weeks or a combination of oral terbinafine 250 mg/day for 16 weeks and topical ciclopirox nail lacquer once daily for 9 months. Both groups were followed up for 9 months from start of treatment. RESULTS: After 9 months of treatment, the mycological cure rates were 22/34 (64.7%) for the terbinafine-only group and 30/34 (88.2%) for the combination therapy group (p<0.05). No significant difference was noted in the complete cure rate. CONCLUSION: Combination therapy of oral terbinafine and ciclopirox nail lacquer is a safe and more effective treatment for onychomycosis than terbinafine alone, especially in younger patients and in shorter-duration onychomycosis.

Administration, Oral↗

Crystallographic structure of enamel surfaces treated with topical fluoride agents: TEM and XRD considerations.

The crystallographic structure of surface coatings produced by three topical fluoride agents deposited by a single application on intact human enamel surfaces was investigated by light- and dark-field transmission electron microscopy, as well as by electron and x-ray diffraction. The agents studied were an acidic silane fluoride lacquer, a neutral NaF lacquer, and an APF gel. The smallest coherently diffracting particles were CaF2 microcrystallites 4-15 nm in diameter. Large apatite-like crystals, approximately 1 micron in length, were also observed in the outer surface coating produced by the silane fluoride lacquer.

Animals↗

[The fluorescein angiography and indocyanine green angiography of high myopia with macular hemorrhage].

OBJECTIVE: To investigate the causes and fundus changes of high myopia with macular hemorrhage. METHODS: Color photography and fundus fluorescein angiography (FFA) were performed on 35 patients (37 eyes) of high myopia with macular hemorrhages, and indocyanine green angiography (ICGA) was performed on 8 patients. RESULTS: The causes of high myopia with macular hemorrhage could be divided into two forms: (1) macular hemorrhage with subretinal neovascularization (23 eyes), (2) macular hemorrhage without subretinal neovascularization (14 eyes). ICGA noted the neovascularization more well-defined and slightly bigger than FFA. In 9 of 14 eyes, lacquer cracks appeared at the sites of macular hemorrhage or around the hemorrhage. 6 eyes were followed up, the follow-up period ranging from 3 to 20 months (mean, 8.6 months). ICGA was performed on two patients. The results show that the rupture of choriocapillaries and Bruch's membrane can result in hemorrhage without subretinal neovascularization, and ICGA is more sensitive in detecting the lacquer cracks than FFA. CONCLUSION: Subretinal neovascularization and the formation of lacquer cracks result in two forms of high myopia with macular hemorrhage. ICGA combined with FFA is more useful in evaluating the two forms of hemorrhage.

Adolescent↗

Ciclopirox topical solution, 8% combined with oral terbinafine to treat onychomycosis: a randomized, evaluator-blinded study.

This randomized, evaluator-blind, 3-arm parallel, comparator controlled, multicenter pilot study evaluated the safety and efficacy of ciclopirox nail lacquer topical solution, 8% in combination with oral terbinafine for the treatment of moderate to severe toenail onychomycosis (> or =60% disease involvement of target nail and/or lunula/matrix involvement) (N = 73). Patients were randomized to 1 of 3 treatment arms: ciclopirox nail lacquer once daily for 48 weeks plus 4 weeks of terbinafine 250 mg/day, followed by 4 weeks of rest (no terbinafine), then another 4 weeks of terbinafine 250 mg/day (PLs); ciclopirox nail lacquer once daily for 48 weeks plus terbinafine 250 mg/day for 12 weeks (PL12); or terbinafine 250 mg/day for 12 weeks (L12). At week 48, mycological cure (negative microscopy and culture) occurred in 66.7% (14/21) (PL8), 70.4% (19/27) (PL12), and 56.0% (14/25) (L12) of patients confirmed dermatophyte positive, respectively (P: not significant). At this time point, effective cure (simultaneous mycological cure and > or =90% reduction in the disease area) was observed in 40.0% (8/20), 33.3% (8/24), and 34.8% (8/23) of patients, respectively (P: not significant). The PLs regimen was well-tolerated and had high compliance. The data suggest that combination therapy (PL8) may be an alternative regimen to continuous terbinafine (L12) in the treatment of moderate to severe dermatophyte toenail onychomycosis.

Administration, Topical↗

Biomonitoring of 2-(2-alkoxyethoxy)ethanols by analysing urinary 2-(2-alkoxyethoxy)acetic acids.

2-Methoxyacetic and 2-ethoxyacetic acids are well known toxic metabolites of 2-alkoxyethanols. The use of 2-alkoxyethanols is now restricted, and the regulations have forced manufacturers to find substitutive solvents, 2-(2-alkoxyethoxy)ethanols. 2-(2-Alkoxyethoxy)ethanols resemble 2-alkoxyethanols, and their most hazardous similarity is their ability to metabolize to the 2-(2-alkoxyethoxy)acetic acids. In the present study, floor lacquerers' (n = 22) inhalation and total exposure to 2-(2-alkoxy)ethoxyethanols was measured. The measurements of inhalation exposure were done with charcoal tubes, and total exposure was biomonitored by urinalysis of 2-(2-alkoxyethoxy)acetic acids. The 8h inhalation exposures of floor lacquerers to 2-(2-methoxyethoxy)ethanol (DEGME), 2-(2-ethoxyethoxy)ethanol (DEGEE) and 2-(2-butoxyethoxy)ethanol (DEGBE) were in average 0.23 +/- 0.07 ppm (average+/-S.D., n = 3), 0.08 +/- 0.07 ppm (n = 16), and 0.05 +/- 0.03 ppm (n = 16), respectively. The excretions of 2-(2-methoxyethoxy)acetic acid (MEAA), 2-(2-ethoxyethoxy)acetic acid (EEAA) and 2-(2-butoxyethoxy)acetic acid (BEAA) were in average 4.9 +/- 4.3 mmol/mol creatinine, 9.3 +/- 8.0 mmol/mol creatinine and 9.2 +/- 7.4 mmol/mol creatinine, respectively. A linear relationship was found between the urinary 2-(2-alkoxyethoxy)acetic acid concentrations and the preceding 8-h occupational exposure to 2-(2-alkoxyethoxy)ethanol.

Acetates↗

Evaluation of exposure to 1-alkoxy-2-propanols and 1-(2-methoxy-1-methylethoxy)-2-propanol by the analysis of the parent compounds in urine.

Floor lacquerers' inhalation and total exposure to 1-alkoxy-2-propanols and 1-(2-methoxy-1-methylethoxy)-2-propanol (DPGME) were measured. The total exposure was biomonitored by urinalysis of free unchanged 1-alkoxy-2-propanols and DPGME. The floor lacquerers' 8-h inhalation exposures to 1-methoxy-2-propanol (PGME), 1-butoxy-2-propanol (PGBE) and DPGME were 1.9+/-1.3 (mean+/-S.D., n=15), 1.0+/-1.4ppm (n=11) and 0.2+/-0.3ppm (n=11), respectively. The gravity-corrected urinary excretions of PGME, PGBE and DPGME were 5.3+/-5.4mumol/l, 0.9+/-0.9mumol/l and 1.5+/-2.8mumol/l, respectively. A linear relationship was found between the gravity-corrected urinary excretion of PGME (R(2)=0.82), PGBE (R(2)=0.93) and DPGME (R(2)=0.93) and their preceding 8-h inhalation exposure. The correlations between the uncorrected urinary excretions and inhalation exposures to PGME, PGBE and DPGME was also calculated and found good (R(2)=0.82-0.95). The effect of work strain on the total exposure seemed to be more relevant in the exposure to hydrophilic PGME than in the exposure to more lipophilic PGBE.

Air Pollutants, Occupational↗

Occupational dermatoses from exposure to epoxy resin compounds in a ski factory.

Of 22 workers in a ski factory, occupational allergic contact dermatitis was found in 8. 6 were sensitive to epoxy resin compounds, i.e., epoxy resins, hardeners or diluents, 1 to cobalt in glass-fiber reinforcements, and 1 to formaldehyde in a urea-formaldehyde glue and a lacquer. 4 workers had irritant contact dermatitis from epoxy resin compounds, lacquers, sanding dust, or glass-fiber dust. 3 had contact allergy from a new sensitizer, diethyleneglycol diglycidyl ether, in a reactive diluent. Immediate transfer of workers sensitized to epoxy resin from epoxy exposure prevents aggravation of their dermatitis and broadening of the sensitization to epoxy hardeners, diluents and other compounds.

Adhesives↗

Morphology of enamel surfaces treated with topical fluoride agents: SEM considerations.

Three topical fluoride agents deposited surface coatings of different morphology and thickness on intact human enamel surfaces. The agents studied were an acidic silane fluoride lacquer, a neutral NaF lacquer, and an APF gel. Each agent reacted with the enamel surface differently, producing its own distinctive etching pattern. The smallest particles observed in the surface coatings were from 20 to 30 nm in diameter and appeared to have indistinct morphologies. They often agglomerated into spherical globules ranging from 1-3 micron in diameter.

Acidulated Phosphate Fluoride↗

[Occupational damage of the sense of smell].

Workers occupationally exposed to synthetic lacquers vapours and wood dust underwent olfactometric and laryngological examinations. The findings indicated that the synthetic lacquers vapours induced neurotoxic lesions of the smell sense. The wood dust causes only nasal cavity mucous membrane lesions inhibiting smell stimuli access to the smelling area. It was suggested olfactometric tests should be included into the preemployment examinations.

Adolescent↗

Occupational formaldehyde exposure and increased nasal cancer risk in man.

A comprehensive data linkage system for the detailed investigation of occupational cancer has newly been established in the Danish Cancer Registry, providing employment histories back until 1964. Based on this system a study of 839 cases of cancer of the nasal cavities, sinuses and rhinopharnyx and 2,465 cancer controls diagnosed in Denmark during the period 1970-1982 was conducted. Histories of exposure to formaldehyde, wood-dust and 10 other specified compounds or procedures, were assessed by industrial hygienists unaware of the case-control status of the cancer patients under study. Some 4.2% of the male and 0.1% of the female controls had been exposed to formaldehyde. A statistically significant excess risk (p less than 0.05) for carcinoma of the nasal cavity and sinuses among males with a history of exposure to formaldehyde (RR = 2.8), wood-dust (RR = 2.5) and paint lacquer and glue (RR = 2.1) was found. When adjustment was made for wood-dust exposure the relative risk associated with formaldehyde was reduced to 1.6, which is not significantly in excess of 1.0, although still compatible with a 3- to 4-fold increase in risk using conventional 95% confidence limits. The joint action of exposure to wood-dust and formaldehyde was in accordance with an additive effect. The excess risk of sino-nasal cancer with exposure to paint, lacquer and glue remained statistically elevated after adjustment for contemporary exposure to wood-dust and formaldehyde.

Air Pollutants, Occupational↗

Sinonasal cancer and occupational exposure to formaldehyde and other substances.

A case-control study of cancer of the nose and paranasal sinuses was conducted in France to determine whether occupational exposure to formaldehyde was associated with an increased risk of sinonasal cancer. Exposures to 14 other substances or groups of substances were also studied (wood dust, leather dust, textile dust, flour dust, sugar dust, coal/coke dust, nickel compounds, chromium compounds, chromium VI, welding fumes, soldering fumes, cutting oils, paints and lacquers, glues and adhesives). Cases (n = 207) and controls (n = 409) were interviewed to obtain detailed information on job history and other potential risk factors for sinonasal cancer. In addition, a questionnaire specially designed for this study was used to help assess exposures to formaldehyde and other substances of interest. The questionnaires were translated into history of occupational exposure by an expert in industrial hygiene, without knowledge of case-control status. Several exposure variables (lifetime average level, duration, cumulative level) were used to describe the risk related to exposure to formaldehyde. Potential confounding factors (occupational and non-occupational) were examined and adjusted for when necessary. No significant association was found between exposure to formaldehyde and squamous-cell carcinomas of the sinonasal cavities. Because of the strong association between exposure to wood dust and nasal adenocarcinoma, it was not possible to assess an independent effect of formaldehyde on this type of cancer. However, among males exposed to medium or high levels of wood dust, the risk of adenocarcinoma associated with formaldehyde was significantly elevated for the highest exposure categories for average level (OR = 5.3, 95% confidence interval = 1.3-22.2), cumulative level (OR = 6.9, 95% CI = 1.7-28.2) and duration of exposure (OR = 6.9, 95% CI = 1.7-27.8). Although a residual confounding effect of wood dust could not be excluded, this study suggests that exposure to both formaldehyde and wood dust may increase the risk of nasal adenocarcinoma, by comparison with the risk due to wood dust alone. This study also indicated an increased risk among males who had been exposed to glues and adhesives, for all histologic types, which was not explained by a confounding effect of paints and lacquers, wood dust or formaldehyde. No other significant association was observed.

Adenocarcinoma↗

Determination of dietary tin intake in an adult French citizen.

The tin contents in fresh food or in food stored in lacquered or unlacquered cans were determined in order to estimate the daily tin intake in a French citizen. Tin levels were 76.6 +/- 36.5 mg/kg in foods preserved in unlacquered cans, 3.2 +/- 2.3 mg/kg in foods stored in lacquered cans, and 0.03 +/- 0.03 mg/kg in fresh foods. Tin intake is essentially dependent on food stored in tin cans (98%), which only represents 5.6% of the total daily consumption of foods by a French citizen. The estimated tin intake (2.7 mg/day whether 0. 04 mg/kg of body weight) remains widely inferior to the daily tolerable dose in humans (2 mg/kg of body weight).

Adult↗

Modification of lignin for the production of new compounded materials.

The cell walls of woody plants are compounded materials made by in situ polymerization of a polyphenolic matrix (lignin) into a web of fibers (cellulose), a process that is catalysed by polyphenoloxidases (laccases) or peroxidases. The first attempt to transform the basic strategy of this natural process for use in human craftsmanship was the ancient lacquer method. The sap of the lacquer tree (Rhus verniciflua) contains large amounts of a phenol (urushiol), a polysaccharide and the enzyme laccase. This oil-in-water emulsion solidifies in the presence of oxygen. The Chinese began using this phenomenon for the production of highly creative artwork more than 6,000 years ago. It was the first example of an isolated enzyme being used as a catalyst to create an artificial plastic compound. In order to apply this process to the production of products on an industrial scale, an inexpensive phenol must be used, which is transferred by an enzyme to active radicals that react with different components to form a compounded material. At present, the following approaches have been studied: (1) In situ polymerization of lignin for the production of particle boards. Adhesive cure is based on the oxidative polymerization of lignin using phenoloxidases (laccase) as radical donors. This lignin-based bio-adhesive can be applied under conventional pressing conditions. The resulting particle boards meet German performance standards. By this process, 80% of the petrochemical binders in the wood-composite industry can be replaced by materials from renewable resources. (2) Enzymatic copolymerization of lignin and alkenes. In the presence of organic hydroperoxides, laccase catalyses the reaction between lignin and olefins. Detailed studies on the reaction between lignin and acrylate monomers showed that chemo-enzymatic copolymerization offers the possibility to produce defined lignin-acrylate copolymers. The system allows control of the molecular weights of the products in a way that has not been possible with chemical catalysts. This is a novel attempt to enzymatically induce grafting of polymeric side chains onto the lignin backbone, and it enables the utilization of lignin as part of new engineering materials. (3) Enzymatic activation of the middle-lamella lignin of wood fibers for the production of wood composites. The incubation of wood fibers with a phenol oxidizing enzyme results in oxidative activation of the lignin crust on the fiber surface. When such fibers are pressed together, boards are obtained which meet the German standards for medium-density fiber boards (MDF). The fibers are bound together in a way that comes close to that by which wood fibers are bound together in naturally grown wood. This process will, for the first time, yield wood composites that are produced solely from naturally grown products without any addition of resins.

Biopolymers↗

Treatment of onychomycosis: pros and cons of antifungal agents.

BACKGROUND: Antifungal agents are beneficial in the treatment of onychomycosis in the general population, as well as in children, the elderly, and immunocompromised individuals. Special patient populations can be more difficult to treat due to such factors as drug interactions with concomitant medications, adverse events, and poor compliance. In addition, there is limited information about the use of antifungal agents in special populations, e.g., children. OBJECTIVE: The pros and cons of oral and topical antifungal agents are discussed, with focus on special patient populations. METHODS: We searched MedLine (1966 to April 2003) for clinical studies evaluating the efficacy of oral and topical antifungal agents to treat onychomycosis. The key words used in conjunction with "onychomycosis" include: "terbinafine," "itraconazole," "fluconazole," "amorolfine nail lacquer," "ciclopirox nail lacquer," "HIV," "transplant patients," "diabetes," "children," and "elderly." Studies were excluded if published in a language other than English. RESULTS: Studies have shown that antifungal agents can be of benefit in treating the elderly, children, and immunocompromised individuals (e.g., transplant patients, Down's patients, HIV patients, and diabetics) with onychomycosis. CONCLUSION: The treatment modality of onychomycosis in special patient populations should take into account the clinical presentation of the onychomycosis, the causative organism, patient and physician preference, the concomitant medications that the patient is on, and the potential for adverse events for that patient if antifungal therapy is undertaken.

Administration, Oral↗

Magnetic susceptibility of laccases and ceruloplasmin.

1. Recent magnetic susceptibility measurements on laccase (monophenol,dihydroxyphenylalanine:oxygen oxidoreductase, EC 1.14.18.1) from the lacquer tree Rhus vernicifera showed a deviation from Curie behaviour above 50 K, which was taken as evidence for an antiferromagnetically coupled Cu(II)-Cu(II) pair in the oxidized enzyme. The magnetic susceptibility of this protein has been reinvestigated. Further measurements on laccase from the fungus Polyporus versicolor and human ceruloplasmin (iron(II):oxygen oxidoreductase, EC 1.16.3.1) are presented. 2. The magnetic susceptibility of fungal laccase and lacquer tree laccase can be accounted for by the EPR detectable copper ions in the temperature range 40--300 K. 3. If an antiferromagnetically coupled Cu(II)-Cu(II) pair exists in the laccases, then the coupling, expressed as --J, should be at least of the order of 300 cm-1, as deduced from the Curie dependence of the susceptibility and the sensitivity in our measurements. 4. If an analogy with the laccases is assumed for the EPR invisible copper in ceruloplasmin then a limiting value of the coupling may be deduced also in this case, with --J at least of the order of 200 cm-1.

Catechol Oxidase↗

New material for low-cost intraocular lenses.

A UV-hardening lacquer material based on polyurethane, used in Philips compact disc lens systems, was tested as suitable material for low-cost intraocular lenses (IOLs). A slightly changed composition (code number I-0.5A) came out as the best and was subsequently tested, with reference to poly(methyl methacrylate) (PMMA), as a 'lobster-claw' lens in Hollander rabbit eyes for a period of 24 wk. No carcinogenic effects were found, while only minor vascularization of the cornea at the incision area occurred. The in vitro biocompatibility tests of the material were positive. Scanning electron microscopy images of the IOLs at 2, 6, 12 and 24 wk postoperative showed portions of an acellular membrane, multinuclear giant cells which hyalinize and stay as pigmented plaques, microphages and fibroblasts with fibrillar strands, long pseudopodia, and broad microplicea. The chosen UV lacquer showed a foreign body reaction and properties comparable with PMMA, and is suitable for manufacturing low-cost IOLs.

Animals↗

Indocyanine green angiographic features of pathologic myopia.

PURPOSE: To analyze indocyanine green angiographic findings of pathologic myopia and compare them with those of fluorescein angiography, with particular reference to the usefulness of indocyanine green angiography in the management of neovascular complications. METHODS: Thirty-two consecutive patients (52 eyes) with pathologic myopia underwent a complete ophthalmologic examination including fluorescein and indocyanine green angiography. RESULTS: Retrobulbar arteries and veins were visualized solely on indocyanine green angiography in 33 (63%) of 52 eyes. Choroidal arteries appeared attenuated and reduced in number. In the area of staphyloma, choroidal veins were less numerous, and in all eyes an absence of the normal choroidal flush caused by the choriocapillaris filling was observed. Subretinal and retinal hemorrhages were present in 28 (54%) of 52 eyes. Choroidal neovascularization was diagnosed in 16 eyes on fluorescein angiography and in 18 eyes on indocyanine green angiography. In seven eyes, indocyanine green angiography disclosed lacquer cracks (without choroidal neovascularization), appearing in the late phases as hypofluorescent lines, as the probable cause of the subretinal and retinal hemorrhages. In only one eye did indocyanine green angiography fail to disclose choroidal neovascularization detectable on fluorescein angiography. In two eyes, neither dye could clarify the origin of the hemorrhages. CONCLUSIONS: Indocyanine green angiography allows identification of retrobulbar arteries and veins, and analysis of the altered choroidal vasculature. Moreover, indocyanine green angiography is a useful diagnostic tool to differentiate lacquer cracks from choroidal neovascularization in retinal and subretinal hemorrhages.

Adolescent↗

Myopic cracks, angioid streaks, and traumatic tears in Bruch's membrane.

We studied the pattern of break formation in 60 eyes with myopic lacquer cracks, angioid streaks, or traumatic tears in Bruch's membrane, using a graphics composition technique and computer analysis of digitized images. Lacquer cracks were found in a reticular distribution within a posterior staphyloma; angioid streaks occurred in a spider-web configuration centered on the optic nerve; traumatic tears were characteristically curved, perineural, and eccentric temporally. The specific break patterns imply the operation of biomechanical forces.

Adolescent↗