Search

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ajo.2009.09.023 Byline: Roger Vogel (a), R. Stephens Crockett (b), Neal Oden (c), Terry W. Laliberte (d), Luis Molina (d) Abstract: To evaluate the efficacy and safety of 0.18% sodium hyaluronate ophthalmic solution (Rejena, Vismed) compared with its vehicle for the treatment of signs and symptoms of dry eye disease. Author Affiliation: (a) Rx Development Resources, LLC, Tampa, Florida (b) Design and Analysis of Trials Associates, Inc, Grand Bay, Alabama (c) The EMMES Corporation, Rockville, Maryland (d) Lantibio, Inc, Chapel Hill, North Carolina Article History: Accepted 30 September 2009

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ajo.2007.06.012 Byline: Alan L. Robin (a)(b)(c), Gary D. Novack (d), David W. Covert (e), R. Stephens Crockett (f), Tania S. Marcic (c) Abstract: To determine with electronic monitoring an objective measurement of adherence in two populations of subjects: those using once-daily prostaglandin analogs as sole ocular hypotensive therapy (one-drug group) and those requiring an adjunctive medicine to the prostaglandin analog (two-drug group). Author Affiliation: (a) Wilmer Institute, Johns Hopkins University, Baltimore, Maryland (b) Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland (c) Mid Atlantic Glaucoma Experts, Baltimore, Maryland (d) PharmaLogic Development, Inc, San Rafael, California (e) Alcon Research Ltd, Fort Worth, Texas (f) D.A.T.A, Inc, Mobile, Alabama. Article History: Accepted 5 June 2007

This volume draws together the final outputs of the five-year UNESCO / IUGS / IGCP Project 571 and presents new data on radon in the built and natural environments, radon as a diagnostic tool of geophysical phenomena, reflections and recommendations on the future of radon research and a critique of radon's asserted use as a therapy. In recent years there has been an increasing interest in radon from a range of different aspects and we would suggest that radon science has the potential to be a useful tool in understanding our environment as well as its impacts on human health.

Context. Type II-linear supernovae are thought to arise from progenitors that have lost most of their H envelope by the time of the explosion, and they are poorly understood because they are only occasionally discovered. It is possible that they are intrinsically rare, but selection effects due to their rapid luminosity evolution may also play an important role in limiting the number of detections. In this context, the discovery of a subluminous type II-linear event is even more interesting.

The surface of human and bovine articular cartilage was imaged with environmental SEM and AFM. The effective modulus of the surface, from force--distance curves obtained with AFM, remained constant at 9±2 kPa in the presence of synovial fluid. Extensive washing of the cartilage surface with phosphate buffered saline (PBS) removed a superficial gel-like layer, leaving a granular layer intact. Force--distance curves showed that the chemical and mechanical properties of the gel exposed to PBS changed over time. The effective modulus at the surface dropped from 481 to 4 kPa over an hour. The results suggest that the gel-like layer, having partly lost water through evaporation on removal from the joint, absorbs water from PBS. It becomes softer and eventually begins to dissolve. The low effective modulus of the gel-like layer in synovial fluid indicates that it is too soft to influence the surface roughness. Imprints of the surface under pressure were taken using a low viscosity dental kit. Imaging of the imprint surface indicated that the topography of the cartilage under pressure was similar to that of the surface after removal of the gel-like layer. In conclusion, imaging of articular cartilage with ESEM and AFM revealed two distinct non-fibrous layers, which are granular and gel-like, and cover the fibrous collagen matrix.

ABSTRACTPurpose:A new formulation of timolol with sorbic acid, timolol-LA (TLA) (Istalol†), has been developed which increases its ocular bioavailability. In the present study, we desired to evaluate the ocular comfort and systemic bioavailability of TLA in healthy volunteers in comparison to standard timolol maleate ophthalmic solution (TIM). †Istalol is a trade name of ISTA Pharmaceuticals, Irvine, CA, USAMethods:This study was a randomized, double-masked, active-controlled, crossover evaluation of 0.5% TLA and 0.5% TIM, bid, in 12 normal healthy volunteers. Visits were at Days 0, 1, 2, 4 and 8 in each period, and there was a minimum 7 day interperiod washout.Results:At all three post-dosing evaluation times (Day 1: Peak, Day 8: Trough, and Day 8: Peak), the 95% confidence interval for the difference between TLA and TIM was not more than 0.37 ng/mL. After administration of TLA, there was a greater incidence of burning/stinging and tearing, but not foreign body sensation, relative to TIM. In general, most symptoms were mild in intensity, and no subject discontinued treatment due to ocular discomfort. Both treatments decreased IOP to a similar level.Conclusion:TLA was relatively comfortable, with a safety profile consistent with further clinical development, and, with bid dosing (exaggerated [2X] that anticipated for clinical use), had a systemic bioavailability similar to that of TIM 0.5%, bid. The incidence of burning and stinging was higher with TLA than with TIM, although reports were mild in severity and did not result in any patient discontinuations. Although the results are of interest, further evaluation in a larger trial may be warranted.

Light damages the cultured bovine retinal epithelium at about the same intensities as those effective in the primate retina, in vivo. Also as in vivo, blue light (457.9 nm) is substantially more damaging than longer wavelengths of the visible spectrum. Experiments were performed to test whether this damage by light is mediated by a photodynamic reaction. Primary confluent monolayer cultures of the bovine retinal epithelium were exposed to 435 nm light for 120 minutes, during which time the oxygen content in the gas phase of the exposure chamber was maintained at a predetermined value. Prior to and after light exposure the cultures were aerated by 20% oxygen. The normal growth medium (Eagle's MEM + 10% fetal calf serum) was used during exposure. Light microscopic and EM examination 24 hours after exposure showed that changes indicating cell death were enhanced by a factor of 10 when exposures were conducted in an atmosphere of 95% oxygen instead of 20% oxygen. No damage at intensities up to 50 mw/sq.cm. was observed with a 0% oxygen atmosphere. These effects were the same when a saline, bicarbonate buffered medium was used during exposure. It is concluded that short wavelength light damage to the retinal epithelium is caused by a photodynamic reaction, i.e. a photosensitized aerobic oxidation. This is the first time that the mechanism of blue light damage on a retinal tissue has been established. The results suggest that light damage in the primate retina, which characteristically involves not only photoreceptors and epithelium but also cells in the other layers, has the same mechanism of light-induced pathology that has been observed in a variety of non-ocular tissues.

Povidone-iodine is frequently instilled on to the conjunctival surface prior to intraocular surgery in order to prevent septic endophthalmitis. A small amount of povidone-iodine is inevitably introduced into the eye when it is used in this manner. The toxicity of intravitreal povidone-iodine was assessed in rabbit eyes by injecting 0.1 ml of povidone-iodine in concentrations of 0.05%, 0.5% and 5% into the vitreous cavity. The injected eyes were evaluated by clinical examination, anterior segment and fundus photography, endothelial cell counts, electroretinography and histopathology. Compared to control eyes, no changes were observed in all 6 eyes injected with 0.1 ml of 0.05% povidone-iodine solutions. 9 of 10 eyes tolerated a concentration of 0.5% with no detectable adverse changes. One eye developed a temporary mild iritis and mild suppression of the ERG. Intraretinal hemorrhages, edema, arteriolar narrowing and retinal edema were seen one week following injection. Mild retinal necrosis of the same area was seen on histology. All 4 eyes injected with 5% povidone-iodine developed temporary hypotony and iridocyclitis. A dense cataract developed in all eyes. Full thickness retinal necrosis and a profound lasting reduction in the ERG was produced in all of these eyes. No corneal epithelial or endothelial changes were observed in any eye in this series. Low concentrations of intravitreal povidone-iodine likely to be produced by instillation prior to surgery are tolerated by rabbit eyes. The concentrations tolerated by the studied eyes are near reported bactericidal levels.

Loteprednol etabonate is a novel site-active corticosteroid synthesized through structural modifications of prednisolone-related compounds so that it will undergo a predictable transformation to an inactive metabolite. In double-masked studies, loteprednol etabonate was effective in the treatment of giant papillary conjunctivitis, seasonal allergic conjunctivitis, postoperative inflammation, and uveitis. The objective of this analysis was to determine the incidence of clinically significant elevations in intraocular pressure (IOP) with long-term use of loteprednol etabonate.

No single drug or combination of drugs was used routinely in pediatric emergency departments to sedate children for suturing. A meperidine-promethazine-chlorpromazine “cocktail” was chosen most frequently. Many physicians were dissatisfied with the method they selected, however, leading some to experiment with newer medications such as fentanyl. The American Academy of Pediatrics (AAP) guidelines for the elective use of conscious sedation, specifically, those regarding monitoring during sedation and discharge post sedation, were not adhered to uniformly. Further study of conscious sedation in children is needed.

The radical cation of 2,5-dimethyl-2,4-hexadiene is identified by ESR upon adsorption of the parent molecule on activated H-mordenite. The same radical is observed when 2,3-dimethyl-1-butene or 2-methylpropene is adsorbed. This is clear evidence for highly specific dimerisation-fragmentation reactions of the primary radical cations in the zeolite at room temperature.

A new chimical method is related allowing to determine automatically the quantity of components in normal aqueous humour. The first results concern proteins, sodium, potassium and chloride. A method for manual measurement of the quantity of ascorbic and is also related. This work is a preliminary report before the study of pathological changes which will be published later on.

Solid free-form fabrication methods are surveyed. This approach of making objects by depositing material layer by layer lends itself to the direct conversion of fluid reactants to a solid part, as opposed to the production of a material and its subsequent processing. Examples are given of the formation of ceramics, metals, thermoplastics, thermosets, and composites. In principle, mobile products can be removed from the layers as they form, allowing a much wider range of reactions to be used. Since the composition may be varied as the object is built up, it is also possible to combine several materials into a monolithic piece.

Radon gas has been shown to cause an increased incidence of lung cancer. In affected areas, levels in the overground workplace can be sufficiently high to be a health risk and remediation is required. In the UK, the workplace Action Level is 400 Bq m−3. The variation of radon levels in the workplace was studied both before and after remediation. In most rooms, remediation resulted in a greater reduction at night than during the working day. The dose reduction, and therefore the health benefit, to workers is less than that predicted by the drop in radon averaged over 24 h. In order to obtain a health benefit to 75% of workers in our series, the 24 h average radon level in each room must be reduced to <225 Bq m−3. It is recommended that UK Regulatory Agencies adopt a post-remediation workplace Action Level of 225 Bq m−3.

Purpose: There is a growing interest in developing drugs for the treatment of pediatric diseases. Combining pediatric development with chronic use and prevention of disease progression indication(s) present special challenges to the clinical pharmacologist. Myopia is a very prevalent disease (up to 80% in some countries), for which current treatments meet only the optical pathology, not ocular comorbidity, or the underlying structural abnormality. Pirenzepine is a m1-selective muscarinic antagonist, long used orally in Europe, and effective in animal models of myopia.Methods: Valley Forge developed a stable ophthalmic gel. The ocular safety and tolerance of PIR was investigated in a short-term study with two year follow-up in myopic children. Subsequently, multi-year, worldwide studies were conducted on the safety and efficacy of the highest tolerated concentration.Results: In an initial Phase 2 study, myopic children tolerated up to 2% PIR. In two subsequent one year Phase 2 studies, 2% PIR, b.i.d. reduced the rate of progression of myopia by ∼50%. While there were some traditional m3-antagonist undesirable effects observed (e.g., mydriasis, accommodation complaints), they were for the most part not therapy limiting, and were much less than expected from a non-selective muscarinic antagonist such as atropine.Conclusions: PIR presents promise as a chronic treatment for prevention of disease progression for pediatric myopia. A continuing development program is planned.Clinical Pharmacology & Therapeutics (2004) 75, P23–P23; doi: 10.1016/j.clpt.2003.11.086

Title compounds (III) are prepared from amidrazones (I) (and some labeled isotopomers) and transformed to radicals (V) via salts (IV).