Objective. To assess the risk of perforation or hemorrhage of peptic ulcer on treatment with nonsteroidal antiinflammatory drugs (NSAIDs), both as a class and as individual agents.Methods. A case-control study of medication histories in 494 patients and 972 matched control subjects.Results. The increase in risk (odds ratio) with NSAID therapy was 5.1 times the risk in controls. The odds ratio for piroxicam was 6.3 (95% confidence interval [CI] 3.3-12.0), as compared with 2.9 for diclofenac, ketoprofen, and sulindac combined (95% CI 2.0-4.2). The effect of other risk factors was also considered, and the adjusted odds ratios were 4.1 for all NSAIDs, 6.4 (95% CI 2.8-15.0) for piroxicam, and 3.3 (95% CI 2.G5.5) for diclofenac, ketoprofen, and sulindac combined.Conclusion. in other studies. There appear to be differences in risk between agents.It is well known that treatment with nonsteroidal antiinflammatory drugs (NSAIDs) is associated with unwanted gastrointestinal (GI) side effects. Retrospective studies have suggested that NSAIDs are associated with an increased risk of perforated peptic ulcer (1,2), and case-control studies have shown a risk factor of 2-4 for hemorrhage of peptic ulcers (3,4) in patients aged 60 years and over. Data from the UK Committee on Safety of Medicines ( 5 ) showed that for the NSAIDs currently available in New Zealand, reports of GI reactions ranged from 21 to 75 per million prescriptions.To ascertain the relative risks with the various NSAIDs, a case-control study of hemorrhage and perforation of peptic ulcer was begun early in 1986. The aim of this study was to confirm an increased risk of complications of peptic ulcer with NSAIDs and to determine whether there are significant differences between the available agents. PATIENTS AND METHODSSelection of patient population. It was estimated that to detect a 3-fold underrepresentation or a 2-fold overrepresentation in the case group of individual NSAIDs having 15% or more of the market share, and assuming an overall increase in risk of 3-fold, the study would require 450 index patients and 900 control subjects (a = 0.05, p = 1 -0.8). To this end, patients in Christchurch and surrounding areas (population 350,000) who were admitted to the hospital because of GI hemorrhage or possible perforation were identified within 24 hours by either the admitting diagnosis or the findings after admission. All such cases are admitted to

The armoured catfish (Hoplosternum littorale) from the Amazon River system is a facultative air breather that is tolerant to both acidic and hydrogen sulphide rich waters. Facultative air breathing in fishes is known to be an important strategy for surviving hypoxia, but its importance for surviving in acidic and hydrogen sulphide rich waters has not previously been investigated. Air-breathing frequency in H. littorale increased from 2 to 28 breaths/h as the partial pressure of oxygen [Formula: see text] in the water was reduced from 137 to 105 mmHg (1 mmHg = 133.322 Pa). Further reduction in [Formula: see text] to 55 mmHg resulted in a reduction in air-breathing frequency and depression of the metabolic rate. During exposure to acidic water (pH 2.8, [Formula: see text] = 155 mmHg), air-breathing frequency was 28 breaths/h, and during exposure to hydrogen sulphide in water buffered to pH 5.6 (700 μM, [Formula: see text] = 155 mmHg), air-breathing frequency was 40 breaths/h. In fish denied access to air, 200 μM hydrogen sulphide is lethal. Thus, in the armoured catfish, air breathing may be more important for surviving in hydrogen sulphide rich and acidic waters than for surviving in mild hypoxia.

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Purpose: To assess the safety and intraocular pressure (1OP)-lowering activity of 2% dorzolamide (topical carbonic anhydrase inhibitor), compared to 0.5% timolol and 0.5% betaxolol eyedrops.Conclusions: Dozolamide 2% given thrice daily was well tolerated and safe, with a clinically significant effect on IOP comparable to betaxolol 0.5% twice daily, but not as great as timolol 0.5% twice daily.Key words: Dorzolamide, glaucoma, ocular hypertension, topical carbonic anhydrase inhibitor. Methods:A parallel, masked, randomised one-year clinical trial was conducted in 16 patients with open-angle glaucoma or ocular hypertension, being a subset of a multicentre study which enrolled 523 subjects. Patients had IOP > 22 mmHg in one eye at baseline following washout of ocular hypotensive medications and were then randomised in a 3:l:l ratio to receive 2% dorzolamide thrice daily, 0.5% timolol twice daily or 0.5% betaxolol twice daily respectively. IOP was measured at Hour 2 (morning peak), Hour 5 and Hour 8 (afternoon trough for dorzolamide) at baseline, Weeks 2 and 4 and Months 2, 3, 6, 9 and 12.Results: Topical dorzolamide 2% solution was well tolerated and safe. Mean IOP for dorzolamide at Hour 2 was 29.1 mmHg at baseline and 20.8 mmHg on treatment at one year, a 28.5% change. Mean IOP for dorzolamide at Hour 8 was 24.5 mmHg at baseline and 20.2 mmHg on treatment at one year, a 17.6% change. Comparable percent changes for timolol and betaxolol were 43.2/25.7 mmHg at Hour 2 and 21.9/13.5 mmHg at Hour 8 respectively.Ophthalmologists have waited many years for a topical formulation of a carbonic anhydrase inhibitor, in the hope of achieving a therapeutic reduction in intraocular pressure (IOP) without the significant systemic side effects. Dorzolamide 2% (MK-507 -Merck Research Laboratories) is one such ophthalmic preparation which may fulfil this expectation. Pilot studies have shown acceptable ocular toleration and clinically significant pressure-lowering effect when given thrice daily to normal volunteers and to patients with elevated IOP.'" A multicentre trial was conducted by Merck Research Laboratories between January 199 1 and June 1992 to assess both safety and efficacy in a larger group of patients (n = 523) over a whole year? The purpose was to compare dorzolamide 2% thrice daily with betaxolol 0.5% twice and timolol 0.5% twice daily. This paper reports the results of a single-centre subset of that multicentre study, carried out at