Peritoneal dialysis in treatment of diffuse purulent peritonitis]

Hypotensive efficacy and safety of local monotherapy with 0.005% xalathane (once a day) and combined therapy with 0.5% timolol (twice a day) and 2% pilocarpine (3 times a day) are compared in 24 patients with primary open-angle glaucoma. Mean decrease of intraocular pressure was significant in both groups. No side effects of xalathane were recorded. In one case there was a slight reddening of the eye and a sensation of discomfort Pilocarpine therapy was associated with miosis in all patients; half of them complained of obscure vision and headache after instillation. Monotherapy with xalathane is safe sufficiently effective, and comparable to combined therapy with timolol and pilocarpine.     

A double-masked, randomized 1-year study comparing dorzolamide (Trusopt), timolol, and betaxolol. International Dorzolamide Study Group

OBJECTIVE: To investigate the safety profile and efficacy of 2.0% dorzolamide hydrochloride, when administered three times daily for up to 1 year, compared with that of 0.5% timolol maleate and 0.5% betaxolol hydrochloride, each administered twice daily. In addition, the effect of adding dorzolamide to the regimen of patients with inadequate ocular hypotensive efficacy while they were receiving one of the two beta-adrenoceptor antagonists and the effect of adding timolol to the regimen of patients receiving dorzolamide were also evaluated. DESIGN: A double-masked, randomized, parallel comparison. SETTING: Multinational study at 34 international sites. PATIENTS: Five hundred twenty-three patients with open-angle glaucoma or ocular hypertension, 17 to 85 years of age. Patients currently using ocular hypotensive medications were required to undergo a washout. INTERVENTION: Two percent dorzolamide three times a day, 0.5% timolol (Timoptic, Merck, Whitehouse Station, NJ) twice daily, and 0.5% betaxolol solution (Betoptic, Alcon, Fort Worth, Tex) twice daily. RESULTS: At 1 year, the mean percent reduction in intraocular pressure at peak of 2% dorzolamide, 0.5% timolol, and 0.5% betaxolol was approximately 23%, 25%, and 21%, respectively. At afternoon trough, the mean percent reduction in intraocular pressure was 17%, 20%, and 15% for dorzolamide, timolol, and betaxolol, respectively. CONCLUSIONS: The ocular hypotensive efficacy of 2.0% dorzolamide, given three times a day, is comparable with that of 0.5% betaxolol, given twice daily, for up to 1 year. In addition, long-term use of dorzolamide was not associated with clinically meaningful electrolyte disturbances or systemic side effects commonly observed with the use of oral carbonic anhydrase inhibitors.     

Efficacy of silicone punctal plugs as adjuncts to topical pharmacotherapy of glaucoma--a pilot study. Punctal Plugs in Glaucoma Study Group

BACKGROUND: The concept of enhancing the ocular hypotensive effects of topical antiglaucoma medications by impeding lacrimal drainage of medication has been insufficiently studied. This investigation sought to evaluate the effect of bilateral inferior punctal occlusion using silicone punctal plugs on the ocular hypotensive effect of topically applied timolol. METHODS: A randomized, double-masked, cross-over clinical trial was conducted, comparing the ocular hypotensive effect of timolol maleate 0.25 percent, both with and without occlusion of the inferior punctum with the Freeman silicone punctal plug. Following a 2-week washout of topical medication, 17 subjects with early primary open-angle glaucoma or ocular hypertension received one drop of timolol 0.25 percent in each eye with or without punctal plugs in place. Blood pressure, resting pulse rate, and intraocular pressure were measured both before timolol instillation and at intervals of 1, 2, 4, 8, and 12 hours following drop instillation. Following a 2-week washout period, the subjects were evaluated with the alternative treatment. RESULTS: There was no statistically significant difference (p = 0.648) in IOP levels between treatment groups. CONCLUSIONS: This pilot suggests that need for a longer-term study with larger numbers of subjects to evaluate the potential role of silicone punctal plugs to enhance the ocular bioavailability of topically applied antiglaucoma medications.     

Characteristics of histamine-induced leukocyte rolling in the undisturbed microcirculation of the rat mesentery

PURPOSE: To determine the efficacy and safety of latanoprost treatment for 1 year in glaucoma patients, and to evaluate the effects of switching from timolol to latanoprost therapy. METHODS: Latanoprost 0.005% was topically applied once daily without masking for 6 months in 223 patients with elevated intraocular pressure after previous treatment with latanoprost once daily or 0.5% timolol twice daily for 6 months in a multicenter, randomized, double-masked, parallel group study. RESULTS: Compared with baseline values before treatment, a significant (P < .0001) diurnal reduction in intraocular pressure of 6 to 8 mm Hg was maintained with minimal fluctuation for the duration of treatment. When treatment was switched from timolol to latanoprost, intraocular pressure was reduced by 1.5 +/- 0.3 mm Hg (mean +/- SEM; 8% change in intraocular pressure; 31% of the intraocular pressure reduction produced by timolol; P < .001) compared with the change in intraocular pressure in patients remaining on latanoprost therapy. Of the patients initially enrolled, 95% successfully completed treatment. There was a slight overall increase in conjunctival hyperemia in patients who switched from timolol to latanoprost, but no change in those who continued latanoprost. The timolol-induced reduction of resting heart rate returned to baseline levels after switching to latanoprost. Of the 247 patients treated with latanoprost during the masked and/or open-label studies, 12 (5%) demonstrated a definite (n = 4) or possible (n = 8) increase in iris pigmentation. CONCLUSIONS: Latanoprost is a well-tolerated ocular hypotensive agent that appears to be more effective than timolol in reducing intraocular pressure. The increase in iris pigmentation appears to be harmless but requires further investigation.     

A multicenter study comparing dorzolamide and pilocarpine as adjunctive therapy to timolol: patient preference and impact on daily life

BACKGROUND: A multicenter, 4-week, two-period crossover study, comparing 2% dorzolamide three times daily to 2% pilocarpine four times daily as adjunctive therapy to 0.5% timolol twice daily, was conducted on 81 patients with elevated intraocular pressure (IOP). The treatments were evaluated for patient preference, tolerability, impact on daily life, IOP control, and visual-field changes. METHODS: The Comparison of Ophthalmic Medications for Tolerability questionnaire was used to assess patient preference, as well as the perception of side effects and activity limitations resulting from the study medications. IOP measurements and visual-field examinations were obtained at baseline and at the end of each crossover period. RESULTS: Of the 77 patients who participated in both periods, 63 (82%) preferred dorzolamide. Patients who expressed a preference preferred dorzolamide over pilocarpine by a ratio of more than 10:1. Patients reported less interference with their daily life because of side effects and activity limitations while receiving dorzolamide than while receiving pilocarpine. Dorzolamide and pilocarpine were comparably effective in lowering IOP (16% to 17%). Also, significantly more patients reported adverse experiences and discontinued therapy as a result of adverse experiences while receiving pilocarpine than while receiving dorzolamide. CONCLUSION: The results of this multicenter study support those of two previous single-center studies; these results show that dorzolamide was greatly preferred over pilocarpine and had better tolerability and less adverse impact on patients' daily lives than pilocarpine.     

Intraocular pressure in rabbits by telemetry II: effects of animal handling and drugs

PURPOSE: To measure under carefully controlled conditions the effects in the rabbit eye of commonly used therapeutic agents for glaucoma. METHODS: Rabbits were outfitted in one eye with an implantable telemetric pressure transducer and monitored for several months under controlled conditions of light/ dark and handling. Effects of tonometry, handling, water drinking, and instillation of topical ophthalmic medications on intraocular pressure were recorded during each 24-hour day/night cycle. RESULTS: Pneumatonometry, animal handling, and water drinking all had an effect on intraocular pressure that in many instances was of the same magnitude as the effects of pharmacologic agents. Dorzolamide and timolol caused a sustained reduction of intraocular pressure during the nocturnal period. Epinephrine had a biphasic effect, causing an immediate pressure elevation followed by a prolonged depression. Apraclonidine, latanoprost, and pilocarpine had no measurable effect. CONCLUSIONS: Continuous telemetric measurement of intraocular pressure in rabbits permits the measurement of uncontrollable artifacts that occur with tonometric measurements and animal handling. If environmental conditions are rigidly controlled, this method is very sensitive for detecting therapeutic effects of candidates for ocular hypotensive drugs. When healthy animals are used, the method appears to be more sensitive for drugs that affect aqueous humor formation than for drugs that affect aqueous humor outflow resistance.     

The favorable effect of topical betaxolol and timolol on glaucomatous visual fields: a 2-year follow-up study

BACKGROUND: It has been suggested that beta-adrenergic antagonists might have mechanisms of action other than ocular hypotensive effects affecting the visual function in glaucoma patients and that betaxolol might protect the visual field better than others. A randomized, double-blind study was conducted to compare the effects of betaxolol and timolol on visual fields of glaucoma patients. METHODS: Sixty-four glaucoma patients were treated with either 0.5% betaxolol or 0.25% timolol eyedrops twice daily. The Octopus visual field performance was followed up for 2 years and analyzed to find diffuse and localized changes. We analyzed the change in the mean sensitivity (MS) and performed a cluster analysis and clinical assessment of the visual fields in both treatment groups. RESULTS: The mean sensitivity (MS) improved significantly and equally in both treatment groups. There was a tendency towards more improved clusters in the betaxolol group than in the timolol group and more worsened cluster in the timolol group than in the betaxolol group, but the difference was not statistically significant. The clinical assessment also showed no statistically significant difference between the two groups. CONCLUSION: In the present study both betaxolol and timolol had a favorable effect on the visual fields of glaucoma patients. There was no statistically significant difference between betaxolol- and timolol-treated patients either in the change in mean retinal sensitivity or in the change in localized scotomatous areas.     

Cytotoxicity of 1-amino-4-phenyl-1,2,3,6-tetrahydropyridine and 1-amino-4-phenylpyridinium ion, 1-amino analogues of MPTP and MPP+, to clonal pheochromocytoma PC12 cells

AIMS: To compare the tolerability and efficacy of a fixed combination solution of dorzolamide/timolol (Cosopt), administered twice daily with the concomitant administration of its components, dorzolamide (Trusopt) twice daily and timolol (Timoptic) twice daily. METHODS: After a 2 week timolol run in, patients with open angle glaucoma or ocular hypertension were randomised (1:1) to receive treatment with either the dorzolamide/timolol combination solution twice daily (combination) or the dorzolamide solution twice daily plus timolol maleate solution twice daily (concomitant) for 3 months. RESULTS: 299 patients were entered and 290 patients completed the study. Compared with the timolol baseline, additional IOP lowering of 16% was observed at trough (hour 0) and 22% at peak (hour 2) at month 3 in both the concomitant and combination groups. The IOP lowering effects of the two treatment groups were clinically and statistically equivalent as demonstrated by the extremely small point differences (concomitant--combination) observed in this study--0.01 mm Hg at trough and 0.08 mm Hg at peak. The safety variables of the concomitant and combination groups were very similar. Both combination and concomitant therapy were well tolerated and few patients discontinued due to adverse effects. CONCLUSIONS: The dorzolamide/timolol combination solution administered twice daily is equivalent in efficacy and has a similar safety profile to the concomitant administration of the components administered twice daily.     

Seroneutralization of porcine reproductive and respiratory syndrome virus correlates with antibody response to the GP5 major envelope glycoprotein

PURPOSE: To compare the long-term efficacy and safety of brimonidine 0.2% twice daily with timolol 0.5% twice daily in patients with glaucoma or ocular hypertension. METHODS: Of the 926 patients enrolled in the study, 837 met the protocol entry criteria and received either brimonidine 0.2% twice daily (n = 466) or timolol 0.5% (n = 371) twice daily in each eye for 1 year. RESULTS: Brimonidine and timolol significantly reduced mean intraocular pressure (P < .001) from baseline levels at every scheduled follow-up visit, both at hour 2 (peak) and hour 12 (trough). At weeks 1 and 2 and months 3 and 12, significantly greater mean decreases in intraocular pressure (P < .040) at peak were observed in patients treated with brimonidine than those treated with timolol. The mean intraocular pressure decrease at trough was significantly greater for timolol than for brimonidine at each follow-up visit (P < .001). With the exception of ocular allergy (in 11.5% of patients using brimonidine and less than 1% using timolol), fewer than 3% of patients in either treatment group withdrew from the study prematurely as a result of a specific adverse event. Patients receiving timolol experienced significant decreases in heart rate (P < .001) from baseline at all follow-up visits. No significant changes in heart rate were seen in patients treated with brimonidine. Neither medication produced clinically significant changes in blood pressure. CONCLUSION: Brimonidine is safe and effective in the long-term lowering of intraocular pressure in patients with glaucoma or ocular hypertension, with efficacy comparable to that of timolol but without a notable negative chronotropic effect on the heart.     

Expanding role of alpha adrenoceptor blockade in the treatment of benign prostatic hyperplasia

PURPOSE: To evaluate the efficacy and safety of timolol hemihydrate once daily versus timolol maleate gel forming solution once daily in patients with primary open-angle glaucoma or ocular hypertension. METHODS: We prospectively randomized patients with primary open-angle glaucoma or ocular hypertension to receive either timolol hemihydrate 0.5% solution or timolol maleate gel forming solution 0.5% every morning. The primary efficacy variable was the 8:00 AM trough intraocular pressure (IOP) 24 hours after administration. RESULTS: Three months after initiation of therapy, baseline IOP had decreased from 23.6 +/- 1.9 mmHg to 18.3 +/- 2.8 mmHg in the group taking timolol hemihydrate (n = 22) and from 23.7 +/- 2.2 mmHg to 18.4 +/- 3.1 mmHg in the group receiving timolol maleate gel (n = 21) at the 24-hour trough level. This was not a significant difference between groups at 3 months. Also, no difference was observed between groups in the 2-hour post instillation IOP. Visual acuity was decreased in the group receiving timolol maleate gel compared with those receiving timolol hemihydrate one minute after instillation of study medicine at month 3. Otherwise, ocular and systemic safety were similar between groups. No differences between groups in cardiac pulse or systolic and diastolic blood pressure were observed. CONCLUSION: Timolol hemihydrate 0.5% solution given once a day appears to be as efficacious and safe in decreasing IOP as timolol maleate gel 0.5% given once a day.     

Influence of alpha-cyclodextrin and hydroxyalkylated beta-cyclodextrin derivatives on the in vitro corneal uptake and permeation of aqueous pilocarpine-HCl solutions

Interactions in aqueous solution between pilocarpine hydrochloride (P-HCl), a rather hydrophilic drug with good water solubility, and various cyclodextrins (CDs) were described recently. To assess the influence of CDs on the diffusion behavior of pilocarpine, in vitro studies were performed using porcine or bovine corneas as diffusion barriers. The affinity of P-HCl for porcine cornea in the presence of alpha-cyclodextrin (alpha-CD) and (hydroxyethyl)-beta-cyclodextrin (HE-beta-CD) was determined by drug uptake experiments. Additionally, in vitro permeation experiments through bovine corneas were conducted with a modified diffusion device optimized for corneal perfusion studies. The results obtained from the corneal uptake studies indicate that the addition of alpha-CD led to increased tissue drug levels. The increase in permeability of pilocarpine in the presence of alpha-CD was approximately 10-fold (log Papp = -4.87 +/- 0.03) in comparison with plain P-HCl solution (log Papp = -5.89 +/- 0.06). Permeation studies with corneas pretreated with alpha-CD solution revealed enhanced corneal permeability of pilocarpine due to alpha-CD induced membrane effects. The hydroxyalkylated beta-CD derivatives HE-beta-CD (log Papp = -6.27 +/- 0.09) and (hydroxypropyl)-beta-cyclodextrin (HP-beta-CD; log Papp = -6.40 +/- 0.03), however, seemed to cause slightly decreased permeation rates, supporting the concept of an interaction between pilocarpine and the hydroxyalkylated-beta-CD derivatives. Considering physiological compatibility, the addition of CDs seems to be an effective tool to modify and optimize the ocular availability of pilocarpine.     

Children killing children

Tolerance and efficacy of a new combined antiglaucoma drug proxopheline (1% proxodolol and 0.25% clopheline) is assessed. Studies in 43 patients (63 eyes) with open-angle glaucoma showed that a single instillation of the drug decreases intraocular pressure in 1 h and in 93% of patients the hypotensive effect persists for up to 24 h. Prolonged (4 weeks) use of proxopheline resulted in normalization of intraocular pressure in 90% of treated eyes. The main side effect was dryness in the mouth (30%). The hypotensive effect of proxopheline is superior to that of proxodolol, but it involves a higher incidence of side effects, caused by clopheline--another component of proxopheline.     

Drug effects on intraocular pressure and vascular flow in the bovine perfused eye using radiolabelled microspheres

A novel technique is described in which the effect of the beta-adrenoceptor antagonists timolol and carteolol, and the vasodilators sodium nitroprusside (SNP) and verapamil on intraocular pressure (IOP) and the distribution of ocular flow in the bovine arterially perfused eye is investigated using radiolabelled microspheres. At maximum IOP-reducing dose timolol was found to significantly reduce perfusion in the choroid and, at higher dose, it was found to significantly reduce perfusion in the iris. By contrast, a maximal IOP-reducing dose of carteolol markedly reduced perfusion in the iris, ciliary body and choroid. Vasoconstriction induced by carteolol was not inhibited by the alpha-antagonist phentolamine. Against a background of vascular tone induced by noradrenaline, SNP and verapamil were found to significantly increase perfusion in the iris, ciliary body and choroid. The effects of these drugs upon the vasculature of the bovine perfused eye are varied and complex and may not bear a direct relationship to their ocular hypotensive effect.     

Adverse drugs reactions associated with glaucoma medications

We undertook a non-concurrent prospective study of 191 Puerto Rican patients from August 1993 to April 1994. All patients had open angle glaucoma (OAG) (age ranged from 50 to 80 yrs; mean = 65 yrs). Patient's symptomatology associated to side effects of their glaucoma medicadons was reviewed. Incidence percent of ocular and/or systemic side effects per medication were: levobunolol 45.0%; betaxolol 42.0%; timolol 27.3%; pilocarpine 100%; dipivefrin 14.0%; and acetazolamide 250 mg 64.1%. Incidence percent of ocular and/or systemic side effects of topical beta-blockers used with concomittant medications were determined. Ocular side effects were more frequent in patients using levobunolol 44.2% than in those patients using betaxolol 42.0%, 8.5% of patients using levobunolol did report systemic side effects. No systemic side effects were reported by patients using betaxolol. Ocular side effects in patients using pilocarpine were frequent (100%); whereas the frequency of systemic side effects was low (6.1%). Systemic side effects were common in patients using carbonic anhydrase inhibitors. These results suggest that non-selective and cardio-selective topical Beta-blockers, differ in their ocular or systemic side effects.     

The efficacy and safety of the dorzolamide-timolol combination versus the concomitant administration of its components. Dorzolamide-Timolol Study Group

OBJECTIVE: To evaluate whether a fixed combination of 2% dorzolamide and 0.5% timolol given twice daily showed equivalent efficacy to the concomitant administration of 2% dorzolamide given three times daily and 0.5% timolol given twice daily in patients whose intraocular pressure (IOP) remained elevated during monotherapy with 0.5% timolol twice daily. DESIGN: Multicenter, parallel, randomized, double-masked clinical trial with an open-label extension. PARTICIPANTS AND INTERVENTION: In the masked phase, 242 patients received either the dorzolamide-timolol combination twice daily and placebo three times daily or dorzolamide three times daily and timolol twice daily for up to 3 months. In the open-label extension, 220 patients received the dorzolamide-timolol combination twice daily for up to 9 months. MAIN OUTCOME MEASURES: The criterion for establishing treatment equivalency was a 95% or greater confidence that the absolute difference in the mean change in IOP from baseline was less than 1.5 mmHg between treatments. RESULTS: During 3 months of treatment, the dorzolamide-timolol combination reduced IOP relative to the 0.5% timolol baseline by approximately 14% at hour 0 (just before the morning dose), 20% at hour 2, and 15% at hour 8. The IOP-lowering effect of concomitant therapy with dorzolamide and timolol was approximately 16% at hour 0.20% at hour 2, and 17% at hour 8. At hours 0, 2, and 8, there was greater than 97% confidence that the treatments were equivalent. During the open-label extension, the mean IOP reduction ranged from 14% to 15% at hour 0 and from 20% to 21% at hour 2. The treatment groups were generally comparable in terms of adverse events, symptoms, ocular signs, visual acuity, visual fields, physical examination, and laboratory measures. CONCLUSIONS: The IOP-lowering effect of the dorzolamide-timolol combination is comparable to that of dorzolamide three times daily plus timolol twice daily and is maintained for up to 1 year. The dorzolamide-timolol combination provides clinically important reduction in IOP relative to baseline treatment with timolol alone and is generally well-tolerated for up to 1 year.     

Pilocarpine hydrochloride in ophthalmic solutions: modification of a high-pressure liquid chromatographic determination and survey

Pilocarpine undergoes 2 important reactions in solutions, epimerization to isopilocarpine and hydrolysis to pilocarpic acid. There is no official USP limit for isopilocarpine or pilocarpic acid in pilocarpine hydrochloride ophthalmic solutions. An existing high-pressure liquid chromatographic (HPLC) method was modified by changing the buffer system to permit its use with constant-pressure as well as constant-volume instruments. The procedure separates all 3 components on a cation exchange resin; pilocarpine and isopilocarpine are determined directly and pilocarpic acid indirectly. Ophthalmic solutions and drug substances were obtained from substantially all the United States marketers of pilocarpine opthalmic solutions and were analyzed by the modified HPLC method. Results of the survey show that isopilocarpine is present to the extent of 0.4-3% and pilocarpic acid at levels of 0.6-7% of total alkaloid.     

Efficacy and tolerability of 0.5% timolol maleate ophthalmic gel-forming solution QD compared with 0.5% levobunolol hydrochloride BID in patients with open-angle glaucoma or ocular hypertension

We compared the efficacy of timolol maleate ophthalmic gel-forming solution 0.5% QD with that of levobunolol hydrochloride 0.5% BID, as measured by change in intraocular pressure (IOP), effect on heart rate, and ocular tolerability. The study had a positive-controlled, double-masked, randomized, multicenter, 12-week, two-period (6 weeks each), crossover design. One hundred fifty-two patients with open-angle glaucoma or ocular hypertension were randomized to receive either timolol maleate gel-forming solution QD or levobunolol BID for 6 weeks, followed by a crossover to the alternate treatment. IOP and heart rate were measured at morning trough and peak during weeks 3, 6, 9, and 12. Timolol maleate gel-forming solution QD was comparable to levobunolol BID in reducing IOP at peak and trough. Although the effects on peak heart rate were similar between the two medications, the effect on trough heart rate of timolol maleate gel-forming solution QD was significantly less than that of levobunolol BID (P = 0.001). The incidence of ocular burning and stinging was comparable between the two treatments. Patients experienced significantly more blurred vision when using timolol maleate gel-forming solution than when using levobunolol (P = 0.013). Overall, more patients experienced at least one adverse event when using timolol maleate gel-forming solution. Timolol maleate gel-forming solution QD is as efficacious in reducing IOP as levobunolol BID.     

A case report of two siblings with familial leukoencephalopathy in normotensive male adults with alopecia and lumbago

The aim of the study was to examine the hypotensive efficacy and tolerance of bisoprolol in elderly patients. Sixty patients (40 <65 years and 20 >65 years) with mild-to-moderate essential hypertension (diastolic blood pressure (DBP) between 95 and 109 mm Hg) were included in the study. After a 2-week run-in period on placebo, patients began bisoprolol therapy (5 mg/d) for 12 weeks. After 4 weeks the dose was increased to 10 mg/d in those with a DBP > or =95 mm Hg. Additionally, in 10 patients over 65 years old, 24-h ambulatory BP monitoring (ABPM) was performed, after placebo and after bisoprolol (5 mg) administration. The hypotensive efficacy of bisoprolol in the elderly and younger patients was similar. Before and after treatment the mean difference of systolic BP (SBP) was 19.6 +/- 12.5 mm Hg and DBP 9.6 +/- 6.2 mm Hg in the younger patients and 16.1 +/- 13.6 mmHg and 9.5 +/- 6.0 mmHg in the elderly patients. Bisoprolol produced a similar reduction in heart rate (23.1% vs 17.1%) in the estimated groups. The tolerance of bisoprolol was good in both groups. There were no significant differences in adverse drug reactions between the groups.     

Effect of pilocarpine ocular therapeutic systems on diurnal control of intraocular pressure

The pilocarpine ocular therapeutic system is an innovative ocular drug delivery system which releases pilocarpine into the tear film at a constant rate of 20mug/hr or 40mug/hr. The system was evaluated in 22 hospitalized patients with bilateral open angle glaucoma to determine its ability to control ocular pressure throughout the diurnal interval. Only the right eye of each patient was treated with the pilocarpine ocular therapeutic system; the other eye served as a control. Twelve pressure measurements were made with a noncontacttorometer over a 34-hour test period. In general, the pilocarpine ocular therapeutic system provided satisfactory around-the-clock control of intraocular pressure and was well tolerated by the patients.     

Clinical experience with amrinone in patients with advanced congestive heart failure

To examine the efficacy of chronic amrinone therapy, the drug was administered to 12 patients with advanced congestive heart failure on average for 27.9 days. The majority of patients had a persistent increase in cardiac index and a persistent decrease in systemic vascular resistance. A decrease in pulmonary arterial diastolic pressure was observed after oral amrinone administration in three patients. However, changes in pulmonary arterial pressure were not consistent in response to intravenous administration of the drug. Thrombocytopenia occurred in four patients, hypogeusia was noted by three patients, and dysosmia developed in two patients. The cumulative survival of the amrinone patients was significantly poorer than that of a second group of patients with congestive heart failure having similar symptoms. These findings indicate that there is a subset of patients with congestive heart failure who do not benefit from chronic amrinone administration and that in such patients its use (especially when given concomitantly with potentially toxic and hypotensive drugs) should be extremely guarded.