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Biomedical subjects

M F Sim

Publications and source records attributed to M F Sim.

15 recordsLinked to original sources
PubMed2000

Cost effectiveness analysis of BMD referral for DXA using ultrasound as a selective pre-screen in a group of women with low trauma Colles' fractures.

Measurements of bone density (BMD) are central to the World Health Organisation (WHO) approach to the definition of osteoporosis. Dual energy X- ray absorptiometry (DXA) remains the gold standard technique for measuring the bone mineral density (BMD) but Quantitative Ultrasound (QUS) is an attractive alternative method of bone assessment because it is easy to use and relatively inexpensive. It has been suggested that QUS could be used as a selective population pre-screen, to maximise the cost effectiveness of referral for DXA assessment of BMD. We set out to examine how such an approach might perform in the assessment of women with low trauma Colles' fracture. In 46 women aged 50-80 (mean 67) years we used DXA to measure BMD at lumbar spine and hip, and heel bone ultrasound to measure Broad Band Attenuation (BUA) and Velocity of Sound (VOS). We calculated local costs of pounds sterling 45 for DXA and pounds sterling 15 for QUS. We identified a BUA threshold of 60 dB/MHz as most cost effective as pre-screen, and calculated a sensitivity of 93% and specificity of 84% in identifying those subjects who were subsequently identified as having osteoporosis by DXA. DXA assessment of all patients had a cost of pounds sterling 77 per osteoporotic subject identified. We examined the cost-effectiveness of using QUS as a pre-screen, only referring subjects for more expensive DXA assessment if BUA was less than 60 dB/MHz. However this approach had no advantage, still costing pounds sterling 78 per osteoporotic subject identified. QUS assessment does not appear cost-effective as a pre-screen for DXA, even in this high risk group of women with low trauma Colles' fracture. A QUS pre-screen would only be cost-effective if the scan could be performed at a substantially lower cost.

Absorptiometry, Photon↗
PubMed1994

Assessment of flosequinan's direct effect on human arterial, venous, and cardiac muscle: comparison with other classes of agents used to treat heart failure.

We wished to provide comparative information regarding the direct effects of flosequinan, a novel quinolone under development for treating heart failure, on isolated human arterial, venous, and cardiac muscle. A similar assessment was made for four other agents--milrinone, ouabain, captopril and diltiazem--that have been used to treat heart failure patients, as well as for flosequinoxan, which is the primary metabolite of flosequinan. Flosequinan produced a potent and balanced relaxant effect on norepinephrine (NE)-contracted human arterial and venous smooth muscle, with IC25 values of 0.32 and 0.50 microM, respectively. At higher concentrations, flosequinan also produced a positive inotropic effect on human cardiac muscle (EC25 = 32 microM). A similar pattern of responses was observed with flosequinoxan. The pharmacologic profile obtained for the other agents examined differed from that observed with flosequinan and flosequinoxan in the following ways: Milrinone produced both vascular relaxant and positive inotropic effects, but at comparable concentrations; ouabain produced both vasoconstrictor and positive inotropic effects; diltiazem exerted a vascular relaxant effect at low concentrations and a negative inotropic effect at higher concentrations; and captopril had slight arterial relaxant and negative inotropic effects. These results demonstrate that the pharmacologic profile of flosequinan and flosequinoxan is unique as compared with that of other agents that have been used to treat patients with heart failure.

Captopril↗
PubMed1993

Relationship between inotropic activity and phosphodiesterase inhibition for flosequinan and milrinone.

The goal of this study was to assess the relationship between the positive inotropic response to high concentrations of the vasodilators flosequinan and BTS 53 554 (the sulfone metabolite of flosequinan) and the effect of both compounds on different forms of cyclic nucleotide phosphodiesterase. In addition, the relationship between inotropic activity and phosphodiesterase inhibition for the cardiotonic milrinone was also evaluated. All three agents exerted a positive inotropic effect on human cardiac muscle fibers. The concentration of milrinone required to increase cardiac contractility was comparable to the concentration required to inhibit the milrinone-sensitive subclass of cyclic AMP-specific phosphodiesterase (type III phosphodiesterase). However, no such relationship was observed for flosequinan and BTS 53 554. These results suggest that the cardiac response to high concentrations of flosequinan and BTS 53 554 is not mediated by inhibition of type III phosphodiesterase.

Humans↗
PubMed1992

Differential inotropic effects of flosequinan in ventricular muscle from normal ferrets versus patients with end-stage heart failure.

1. In right ventricular papillary muscles from control ferrets, flosequinan (10(-7)-10(-4) M) produced a concentration-dependent positive inotropic effect (10(-5) M = 153 +/- 24, 10(-4) M = 198 +/- 44% increase in isometric tension; control tension = 100%; n = 11) associated with a corresponding increase in amplitude of the intracellular Ca2+ ([Ca2+]i) transient recorded with aequorin (10(-5) M = 133 +/- 11, 10(-4) M = 187 +/- 36% increase in [Ca2+]i transient; n = 11). 2. The positive inotropic effect of flosequinan in control ferret ventricular muscle was neither blocked by propranolol (6 x 10(-7) M), nor associated with the abbreviation of the [Ca2+]i transient and contraction that is typical of catecholamines. 3. Neither flosequinan (n = 12) nor BTS 53 554, its sulphone metabolite (n = 6) produced a positive inotropic effect or altered the time course of contraction in myocardium from the hearts of patients with end-stage failure. 4. In contrast to milrinone, which produces a positive inotropic effect via phosphodiesterase inhibition, the unresponsiveness of myopathic human myocardium to flosequinan was not restored after intracellular adenosine 3':5'-cyclic monophosphate (cyclic AMP) levels were increased by prior treatment with forskolin (n = 13). 5. Taken together, these data indicate that flosequinan has a direct positive inotropic effect that is Ca(2+)-dependent, but independent of changes in intracellular cyclic AMP concentrations. 6. The positive inotropic effect may be species-dependent or altered by the presence of hypertrophy and/or heart failure. However, when used therapeutically in patients with severe heart failure, our data suggest that flosequinan should not adversely affect myocardial oxygen consumption through direct or catecholamine-mediated actions on the heart.

Animals↗
PubMed1988

Cardiovascular effects of the novel arteriovenous dilator agent, flosequinan in conscious dogs and cats.

1. Flosequinan (BTS 49 465, 7-fluoro-1-methyl-3-methylsulphinyl-4-quinolone) a novel arteriovenous dilator agent was orally effective in conscious renal hypertensive dogs and normotensive cats. The hypotensive potency of flosequinan was approximately ten times less than that of hydralazine in renal hypertensive dogs, 10 mg kg-1 and 20 mg kg-1 flosequinan causing similar falls in mean blood pressure to 1 mg kg-1 and 3 mg kg-1 hydralazine respectively. In normotensive cats, 5 mg kg-1 flosequinan caused similar falls to 0.5 and 1.0 mg kg-1 hydralazine. The onset of hypotensive effect after flosequinan appeared to be slightly slower than after hydralazine in the dog and slightly faster than hydralazine in the cat. 2. The degree of tachycardia and increase in plasma renin activity (PRA) for equivalent falls in mean blood pressure in both species was significantly less for flosequinan than for hydralazine (P less than 0.05). 3. In normotensive dogs, flosequinan, 10 and 20 mg kg-1 orally, caused a small but non-significant increase in sodium and chloride excretion and had little effect on urine volume whereas hydralazine, 1 and 3 mg kg-1 orally, caused a marked retention of sodium and chloride ions and a reduction in urine volume (P less than 0.01). 4. Neither flosequinan, 10 mg kg-1 orally, nor hydralazine 1 mg kg-1 orally, affected either glomerular filtration rate measured as creatinine clearance or effective renal plasma flow measured as p-aminohippuric acid clearance in normotensive dogs. 5. The lesser degree of tachycardia and increase in plasma renin activity together with a lack of sodium retaining activity associated with flosequinan suggest that this agent may have potential advantages over existing therapy as an antihypertensive in man.

Animals↗
PubMed1982

Reduction of the effects of diuretics or sodium chloride loading in the conscious rat by inhibitors of prostaglandin synthesis.

In conscious rats pretreatment with indomethacin or flurbiprofen, two chemically unrelated inhibitors of prostaglandin synthesis, reduced urine volume and sodium excretion induced by four diuretics, acetazolamide, amiloride, bendrofluazide and frusemide, or oral sodium chloride loads. The maximum reduction in sodium excretion was limited to approximately 2 mmol/kg Na+ even when sodium excretion was greatly increased. In contrast these inhibitors did not appreciably affect potassium excretion. These results indicate that part of the natriuretic response in the rat to highly and moderately efficacious diuretics and to sodium chloride loading is modified by prostaglandins. We suggest that the lack of effects on potassium excretion indicate that the collecting tubule is the probable site of action.

Acetazolamide↗
PubMed1981

BTS 39542, a dihydrophthalazin-1-ylacetic acid with high efficacy diuretic activity.

1 BTS 39542, a novel dihydrophthalazin-1-ylacetic acid, has high efficacy diuretic activity in mice, rats, rabbits and dogs. It is twice as potent as frusemide in mice and dogs, ten times as potent in rats and twenty times as potent in rabbits. 2 BTS 39542, like frusemide, exerts its major effects in the loop of Henle and increases renal blood flow but does not affect glomerular filtration rate in dogs. 3 The ratio of the excretion of the major cations (sodium plus potassium) to that of the major anion (chloride) after either BTS 39542 or frusemide varied with species. In rats and rabbits the ratio was approximately unity but in mice and dogs the ratio consistently exceeded unity. 4 A method for evaluating diuretics based on potency and relative potassium excretion is described.

Animals↗
PubMed1977

An investigation of the sex difference in the diuretic response to ethacrynic acid in mice.

1. Female mice of the Hough/Porton and Tuck/TO strains were found to be more sensitive than male mice to the diuretic effects of oral and intravenous doses of ethacrynic acid. 2. The sensitivity of Hough/Porton male mice to ethacrynic acid was increased after pretreatment with stilboestrol and the sensitivity of female Hough/Porton mice decreased after pretreatment with testosterone. 3. There were no significant sex differences in the diuretic response to frusemide, acetazolamide, aminophylline, bendrofluazide, and Su 15049A although a small, but significant, increase in the sensitivity of male Tuck/TO mice to triamterene was noted. 4. The sex difference in diuretic response to ethacrynic acid may be related to an effect of sex hormone balance on its metabolism or on the sensitivity of its renal receptor.

Animals↗
PubMed1976

Effects of various diuretic agents in the mouse.

Diuretic effects of seven orally-acting diuretic agents have been examined in the mouse. The following compounds, examples of various types of orally active compound available, produced their characteristic diuretic effects: bendrofluazide, frusemide, ethacrynic acid, acetazolamide, triamterene, aminophylline and Su 15049A. The diuretic effects of the various agents were demonstrated under both water and saline-loading conditions. After allowing for differences in baseline sodium excretion, all diuretics except acetazolamide caused a further enhancement of sodium excretion after saline-loading compared with water-loading tests. The mouse possesses several advantages over the more commonly used rat since the range of diuretic responsiveness is greater. These results suggest that the mouse is a suitable species for diuretic testing.

Acetazolamide↗