A comparison of the intraocular pressure-lowering effect of 0.5% timolol maleate and the docosanoid derivative of a PGF2 alpha metabolite, 0.12% unoprostone, in subjects with chronic open-angle glaucoma or ocular hypertension.

The efficacy of 0.5% timolol was compared with that of the prostaglandin derivative unoprostone in maintaining control of intraocular pressure (IOP) in subjects with chronic open angle glaucoma (COAG) or ocular hypertension (OH) already responding satisfactorily to beta-blocker monotherapy. In a two-centre, double-masked, randomised parallel group study, 40 subjects were placed on 0.5% timolol eyedrops twice daily for two weeks. They were then randomised either to continue with 0.5% timolol or to switch to 0.12% unoprostone, applied twice daily for six weeks. IOP was measured at two-weekly intervals. The status of the conjunctiva, iris, cornea and anterior chamber was kept under observation. Ocular safety was monitored by measurements of visual acuity, and any systemic adverse events were recorded. After six weeks' treatment, there were no statistically significant differences in mean change from baseline IOP within or between treatment groups. For the subjects treated with unoprostone, mean IOP increased by 0.69 mm Hg (p = 0.368) while that of the timolol-treated subjects fell by 0.47 mm Hg (p = 0.287). The difference in mean IOP between groups was 1.16 mm Hg (p = 0.211, 95% confidence interval [CI] -0.69 to 3.02). The most common complaint was a mild and transient burning sensation on instillation which occurred more frequently in the unoprostone group. In conclusion, an aqueous solution of 0.12% unoprostone isopropyl, applied topically to the eye twice daily for six weeks, was as effective as 0.5% timolol in maintaining control of IOP in subjects with chronic open angle glaucoma or ocular hypertension. Both treatments were safe and well tolerated.

Recovery from pamidronate (APD): a two-year study in the dog.

The goal of this study was to find out if bone can recover after long-term administration of bisphosphonate. Disodium pamidronate (APD) was given orally by gavage to mature beagle dogs at doses of 0, 2.5, 12.5, and 25 mg/kg/day for 1 year (0.1% concentration) and the animals were allowed to recover for another year. At sacrifice, the os ilium was used to determine bone mineralization profile and, subsequently, each density fraction was analyzed chemically. The ribs were used to determine the lattice parameters and the size of the apatite crystals of bone. The sternum was used to determine selected morphometric parameters using image analysis of specimen X-ray films and, subsequently, to determine bone mechanical properties using a 3-point bending technique. We found that the 12.5 and 25 mg/kg/day doses exhibit a significant shift towards greater mineralization versus control, whereas the lower dose (2.5 mg/kg/day) was indistinguishable from the controls. The lattice parameters and crystal size of bone apatite remained unchanged. The image analysis shows a dose-related increase in trabecular volume and thickness. The connectivity increased with dose but the anisotropy of bone remained unchanged. Both the elastic modulus and the maximum stress of bone remain unaffected by APD. We conclude that when dogs are treated with APD for 1 year, their bones can reestablish their physical-chemical characteristics (mineralization profile, chemistry, and crystal size/strain) after 1 year of recovery, provided that the treatment dose is 2.5 mg/kg/day. In addition, the mechanical properties of the bone remained unaffected and the gains in trabecular volume and thickness are maintained.

Changes in bone mineralization, architecture and mechanical properties due to long-term (1 year) administration of pamidronate (APD) to adult dogs.

The goal of this study was to evaluate the effect of 1 year of APD administration on bone mineralization and bone mineral chemistry in the dog. Disodium pamidronate (APD) was given orally by gavage to mature beagle dogs at doses of 0, 2.5, 12.5 and 25.0 mg/kg per day (0.1% concentration for 12 months) as part of a long-term toxicity study. The os ilium and a vertebra were used to determine the mineralization profile and, subsequently, each density fraction was analysed chemically. The ribs were used to determine lattice parameters of the apatite crystal size using X-ray diffraction. The sternum was used to determine selected morphometric parameters using image analysis of specimen X-ray films and subsequently to determine mechanical properties using velocity-of-sound techniques. We found that for both the ilium and the vertebrae there was a significant shift of the mineralization profile towards greater density in a dose-related manner. This effect levelled off with the highest dose because the shift in mineralization profile correlated better with the square root of the dose than with the dose. Together with data on crystal size, which show an increase in lattice parameters and a decrease in crystal size with dose, our data lead us to believe that long-term administration of APD leads to an increase in bone mineralization without major changes in bone chemistry of Ca, Mg, and P and with a decrease in bone apatite crystal size. The image analysis shows a dose-related increase in trabecular bone volume and thickness.(ABSTRACT TRUNCATED AT 250 WORDS)

Rhegmatogenous retinal detachment in a hypertensive dog.

A 4-year-old dog of the Appenzeller strain with experimentally induced renal hypertension presented with apparently longstanding retinal changes, including hemorrhage, detachment, tears/holes, and anemia, in one eye and intravitreal hemorrhage in the other. The retinal tears/holes probably occurred following constant vitreous traction due to retinal hemorrhage and subsequent exsanguination of most of the retinal vasculature. This animal was reexamined six months later and most of these changes had persisted. Photodocumentation is presented.