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Biomedical subjects

A Alm

Publications and source records attributed to A Alm.

At least 55 records · Page 3Linked to original sources
PubMed1995

The short-time effect of latanoprost on the intraocular pressure in normal pressure glaucoma.

Latanoprost, a prostaglandin analogue, was given topically to 20 patients with normal pressure glaucoma in a double masked randomized study. Either latanoprost 0.006% or placebo (vehicle) was administered twice a day for 14 days. Latanoprost caused a statistically significant (p < 0.001) reduction in intraocular pressure from a diurnal baseline level of 16.8 to 14.3 mmHg, as measured on day 14. Latanoprost was well tolerated.

Administration, Topical↗
PubMed1995

Latanoprost administered once daily caused a maintained reduction of intraocular pressure in glaucoma patients treated concomitantly with timolol.

The long term effects of two dose regimens of latanoprost (PhXA41) administered to eyes concomitantly treated with timolol which had not adequately been controlled by timolol alone were compared. A total of 50 patients, 17 with primary open angle glaucoma and 33 with capsular glaucoma, were recruited from five clinics. All had glaucomatous visual field defects and an intraocular pressure (IOP) of at least 22 mm Hg despite treatment with 0.5% timolol twice daily. Patients were randomised to two treatment groups. In one group 0.006% latanoprost was given twice daily, in the other group placebo was given at 8 am and latanoprost at 8 pm for 3 months, with concomitant timolol treatment in both groups. Average daytime IOP (mean (SD)) at baseline (on timolol alone) and after 4 and 12 weeks' treatment was 24.8 (3.6), 16.8 (4.3), and 15.7 (2.4) mm Hg respectively with once daily application of latanoprost and 24.9 (2.9), 18.1 (3.0), and 18.0 (3.6) mm Hg respectively with latanoprost twice daily. No clinically significant side effects were observed during treatment. Latanoprost causes a marked and sustained IOP reduction in eyes which are also being treated with timolol. Latanoprost given once daily is at least as effective and probably superior to a twice daily dose regimen.

Aged↗
PubMed1993

Intraocular pressure-reducing effect of PhXA41 in patients with increased eye pressure. A one-month study.

PURPOSE: To establish the dose-response relationship for the effect on intraocular pressure (IOP) and side effects during long-term treatment of patients with ocular hypertension with the prostaglandin F2 alpha (PGF2 alpha) analog PhXA41. METHODS: A three-center, randomized, double-masked study where IOP, conjunctival hyperemia, and ocular irritation were followed during a 1-month twice-daily treatment with placebo or 35, 60, or 115 micrograms/ml PhXA41 in 60 patients with ocular hypertension, primary open-angle glaucoma, or capsular glaucoma. RESULTS: The three concentrations of PhXA41 reduced the average IOP between 31% and 38% during the second day of treatment, with only a weak dose-response relationship. The initial effect declined somewhat during the first 2 weeks of treatment but then remained at the same level for the rest of the study, with a pressure reduction of approximately 20% for all three concentrations. On the second day of treatment, mild conjunctival hyperemia could be observed in most treated patients. Nineteen of 45 PhXA41-treated patients, compared with 2 of 15 placebo-treated patients, reported to have mild to moderate ocular irritation. These side effects became less pronounced during the study, and at the end there was little difference in the degree of conjunctival hyperemia between placebo- and drug-treated eyes, and no drug-related ocular irritation was reported with the two lowest concentrations of PhXA41. CONCLUSIONS: It is confirmed that the PGF2 alpha analog PhXA41 is a major improvement with respect to the effect-side effect relationship and that it may become a valuable new agent for the treatment of glaucoma.

Adult↗
PubMed1992

The effect of sodium iodate on the blood-retinal and blood-brain barriers.

Both active transport through and permeability of the blood-retinal barrier (BRB) are affected by sodium iodate, while the blood-brain barrier (BBB) is more resistant. We studied the effect of sodium iodate on facilitated diffusion through the two barriers. The retinal (RUI) and brain (BUI) uptake indices were determined for D-glucose and two neutral amino acids in normal and sodium iodate-treated rats. The integrity of the barriers was estimated by RUI and BUI for L-glucose and by measuring tissue uptake of L-glucose after an intravenous injection. We found that 30 mg/kg sodium iodate had no effect on transport through or permeability of the BBB, while 20 mg/kg significantly (P < 0.02) reduced transport of D-glucose, but not amino acids, through the BRB 1 h after injection. After 24 h both 20 mg/kg and 30 mg/kg sodium iodate caused a significant disruption of the BRB (P < 0.005 and P < 0.001, respectively). Thus, sodium iodate selectively affects the carrier for D-glucose in the BRB but not in the BBB. The presence of an epithelial part in the BRB, the retinal pigment epithelium, may explain the difference between the two barriers.

Animals↗
PubMed1992

PhXA34--a prostaglandin F2 alpha analogue. Effect on intraocular pressure in patients with ocular hypertension.

PhXA34, a prostaglandin analogue, was given topically to 40 patients with untreated ocular hypertension in a double masked randomised study. One single dose of 0.3, 1, 3, 10 micrograms, or placebo (vehicle) was given to one eye of each patient. A dose related IOP reduction ranging from 11 to 35% was observed with a maximal effect with 3 and 10 micrograms PhXA34. No hyperaemia was seen except after 10 micrograms PhXA34, where a mild to moderate hyperaemia was seen from 8 hours with a duration of up to 24 hours. Mild foreign body sensation in the PhXA34-treated eye was noted by three patients. No cells or flare were seen.

Adult↗
PubMed1992

[Pharmacology aspects of glaucoma].

The aim of all treatment for glaucoma is to lower intra-ocular pressure. During the past decade, the short-action cholinergic agonists, eserine and pilocarpine, that have been used for over a hundred years have been replaced as the drugs of choice by beta-blockers, in particular the non-selective beta-blocker, timolol maleate. Of the series of drugs developed in recent years for the treatment of glaucoma, two types--carbonic anhydrase inhibitors and prostaglandin analogues--are undergoing phase III trials. The article provides an account of the pharmacological basis of glaucoma treatment today and in the immediate future.

Adrenergic alpha-Agonists↗
PubMed1991

Multiple-dose, dose-response relationship for the topical carbonic anhydrase inhibitor MK-927.

The multiple-dose, dose-response curve of MK-927 was studied in a five-center, double-masked, randomized, placebo-controlled, parallel study of 2%, 1%, and 0.5% MK-927 in 76 patients with bilateral primary open angle glaucoma or ocular hypertension and intraocular pressure greater than 24 mm Hg following washout of ocular hypotensive medications. Patients received doses at 8 AM and 8 PM for 14 days, and parallel 12-hour intraocular pressure curves were performed prestudy and on day 14, with 4-hour curves on days 1 and 4. There was a significant dose-response relationship, with 0.5% MK-927 twice daily being a minimal-effect dose. Both 1% and 2% MK-927 were active through 12 hours postdose, and peak mean percent decrease in pressure at 2 hours postdose was 18.6% and 20.6%, respectively.

Administration, Topical↗
PubMed1991

PhXA34, a new potent ocular hypotensive drug. A study on dose-response relationship and on aqueous humor dynamics in healthy volunteers.

The prostaglandin analogue PhXA34 was tested in two studies in normal human eyes; 1, 3, and 10 micrograms of PhXA34 reduced the intraocular pressure by about 2, 3, and 4 mm Hg, respectively, 6 to 10 hours after a single topical dose. The only side effect observed was a slight conjunctival hyperemia after 10 micrograms of PhXA34. In a second study we determined the effect of 10 micrograms of PhXA34 once daily for 7 days on intraocular pressure, outflow facility, aqueous flow, blood-aqueous barrier permeability, ocular discomfort, and hyperemia. The mean intraocular pressure was below 9 mm Hg 12 hours post dose. About one third of the intraocular pressure reduction could be explained by increased outflow facility. Aqueous flow was unaffected. Treatment caused a 21% increase in aqueous fluorescence 1 hour after an oral dose of fluorescein. Mild ocular discomfort and some hyperemia were initially observed in half of the subjects, but frequency and magnitude of these side effects declined during the study.

Administration, Topical↗
PubMed1991

The effect of diabetes on transport through the blood-retinal and blood-brain barriers in rats.

The uptake-index technique was used to study the effect of streptozotocin-induced diabetes on transport through the blood-retinal (BRB) and blood-brain barriers (BBB) in rats. Untreated diabetes reduced retinal and cerebral uptake of glucose but had no effect on the uptake of L-leucine. A similar reduction in glucose uptake was achieved by an intravenous infusion of glucose in normal rats. Insulin given 1-4 h before the experiments to diabetic rats normalized both blood-glucose levels and retinal and cerebral glucose uptake in diabetic rats. Experiments in hyperglycemic, normal rats suggested that both the preceding plasma glucose level and the concentration of glucose in the injected bolus influence retinal and cerebral uptake of glucose, and we conclude that competitive inhibition may explain the reduction in glucose uptake observed in untreated diabetes.

Animals↗
PubMed1990

The effect of adding prostaglandin F2 alpha-isopropylester to timolol in patients with open angle glaucoma.

Prostaglandin F2 alpha-isopropylester (PGF2 alpha-IE) (0.5 microgram) or placebo was added twice daily for 1 week to one eye in each of 30 patients with open angle glaucoma not adequately controlled with timolol treatment. Compared with placebo, PGF2 alpha-IE reduced the intraocular pressure of these timolol-treated eyes significantly. The absolute difference in mean change between PGF2 alpha-IE and placebo groups was 4.5 mm Hg with a 95% confidence interval of 3.1 to 6.6 mm Hg, corresponding to a mean reduction of initial intraocular pressure of 17.4% in eyes treated with PGF2 alpha-IE. Conjunctival or episcleral hyperemia was seen in all eyes treated with PGF2 alpha-IE for up to 4 hours but not in eyes treated with timolol and placebo, and aqueous flare was not observed in any eye. Thirteen of 15 patients treated with PGF2 alpha-IE, compared with only 3 of 15 who received placebo, reported mild to moderate subjective discomfort in the treated eye in the form of a foreign-body sensation that lasted for up to 2 hours. These results demonstrate that PGF2 alpha-IE, in a dose that has previously been shown to reduce intraocular pressure in normotensive volunteers or in patients with glaucoma who are taking no other medications, also significantly reduces the intraocular pressure of patients with glaucoma whose pressures are not adequately controlled on a twice-daily regimen of timolol.

Dinoprost↗
PubMed1990

Permeability of ocular vessels and transport across the blood-retinal-barrier.

This paper reviews quantitative studies on the permeability of retinal and choroidal vessels and the exchange of nutrients over the blood retinal barrier (BRB). The fenestrated capillaries in the choroid are very permeable to low molecular weight substances; sodium permeability in the choroid is probably 50 times that in skeletal muscle. This results in high concentrations and rapid turnover of nutrients in the extra-vascular compartment of the choroid. Free diffusion is restricted by the pigment epithelium barrier. Also the retinal capillaries, with tight junctions between the endothelial cells, have very low permeability even to sodium. The uptake index technique has provided evidence for several carrier systems in the BRB; hexoses, neutral and basic amino acids, and monocarboxylic acids, very similar to those found in the brain. At least for glucose and lactate these carriers operate at both levels of the BRB; the RPE and the endothelium of the retinal capillaries, and in both directions; i.e. inwards and outwards.

Animals↗
PubMed1990

Effects of D-timolol and L-timolol eye drops on intraocular pressure and aqueous flow. A dose-response study in normal eyes.

The effect on intraocular pressure of 0.5, 1.0, 2.0 or 4.0% D-timolol and 0.25 or 0.5% L-timolol was determined in healthy volunteers after a single topical application. A dose-response relationship for D-timolol could be established. The effect on a diurnal pressure curve and on aqueous humour production was about twice as large with 0.25% L-timolol as with 4.0% D-timolol.

Administration, Topical↗
PubMed1990

The effect of reduced tear drainage on corneal and aqueous concentrations of topically applied fluorescein.

The effect of reduced tear drainage on the intraocular penetration of topically applied fluorescein was studied with fluorophotometry in healthy eyes. Corneal and aqueous fluorescein concentrations could not be followed for the first hour after application of fluorescein because tear film fluorescense influenced fluorophotometric determinations of fluorescein concentrations in cornea and aqueous for at least 30 min. Insertion of punctal plugs in the upper and lower punctum of one eye caused a significant (P less than 0.025) increase in aqueous fluorescein concentrations 1 to 8 h after application of 20 microliters of a 2% solution of sodium fluorescein in the lower conjunctival sac. The achieved concentrations were almost 4 times as large as in the fellow eye. There was some individual variation, but a marked increase was observed in 9 of 11 subjects. Attempts to reduce tear drainage by compressing the tear sac and/or closing the eye lids for 1 min after application of the eye drop had no significant effect on corneal or aqueous concentrations of fluorescein 1 to 8 h later.

Administration, Topical↗
PubMed1990

Ocular effects of two different prostaglandin F2 alpha esters. A doublemasked cross-over study on normotensive eyes.

Ocular hypotensive effects and side effects of two different topically applied prostaglandin (PG) esters were evaluated in a double masked study in 12 healthy males. Three doses of 15-propionat-PGF2 alpha-isopropylester (15-prop-PGF2 alpha-IE), two doses of PGF2 alpha-isopropylester (PGF2 alpha-IE), and placebo were compared. At equipotent doses 15-prop-PGF2 alpha-IE caused similar ocular side effects as PGF2 alpha-IE. It is concluded that both PGF2 alpha-IE and 15-prop-PGF2 alpha-IE reduce the IOP in normal eyes, but the use of a diester such as 15-prop-PGF2 alpha-IE does not provide a better separation between effect on IOP and side effects than PGF2 alpha-IE.

Administration, Topical↗
PubMed1989

Prostaglandin F2 alpha-isopropylester eye drops: effect on intraocular pressure in open-angle glaucoma.

In 30 patients with previously untreated open-angle glaucoma an intraocular pressure (IOP) curve was taken before and during treatment with PGF2 alpha-isopropylester (PGF2 alpha-IE) eye drops in one eye. Compared with the pretreatment IOP, the PGF2 alpha-IE induced a slowly increasing reduction in IOP. Just before the first dose the IOP was 31.4 (SEM 1.6) mm Hg. When corrected for the fall in pressure observed in the fellow eye the largest reduction, 5.8 (SEM 0.7) mm Hg (p less than 0.001), was obtained 24 hours later, that is, 12 hours after the second dose. In a subgroup of 10 patients the treatment was continued for one week. In this group the final pretreatment IOP was 25.9 (SEM 1.3) mm Hg. The reduction 24 hours later was 4.5 (SEM 0.6) mm Hg (p less than 0.001). The effect was maintained and even slightly increased during the week, and on the seventh day of treatment the IOP reduction ranged between 4.8 and 7.6 mm Hg compared with the pretreatment IOP. No serious subjective or objective side effects were observed.

Aged↗