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Biomedical subjects

A J Brady

Publications and source records attributed to A J Brady.

At least 19 recordsLinked to original sources
PubMed2003

The cost-effectiveness of a new statin (rosuvastatin) in the UK NHS.

Statins are central to the government's National Service Framework (NSF) for coronary heart disease (CHD). NHS spending on statins is currently about pounds sterling 500 million per annum and rising at an annual rate of 30%. Although generally considered to be a cost-effective treatment for hyperlipidaemia and cardiovascular disease, given the high and rising expenditure on statins in the UK, there is a pressing need to ensure that the choice between available statins reflects cost-effectiveness considerations. A decision model was developed to establish the cost-effectiveness of treating new hypercholesterolaemic patients to UK and European target levels of blood total cholesterol (TC) and low density lipoprotein-cholesterol (LDL-C), using rosuvastatin, atorvastatin, simvastatin, pravastatin or fluvastatin. The model was used to estimate the proportion of patients reaching target and the associated costs over a one-year period from the perspective of the NHS. The effectiveness of the alternative statins were modelled using data from the Statin Therapies for Elevated Lipid Levels compared Across doses to Rosuvastatin (STELLAR) trial. Monte Carlo simulation was used to reflect uncertainty in the parameter estimates applied in the model. Rosuvastatin is demonstrated to dominate (i.e. lower costs and a higher number of patients treated to target) atorvastatin, simvastatin and pravastatin. Compared with fluvastatin, the incremental cost per additional patient to target (PTT) for rosuvastatin was pounds sterling 24 using LDL-C and pounds sterling 83 using TC. The probability that rosuvastatin is cost-effective exceeds 95%, provided the NHS is prepared to pay at least pounds sterling 35 per PTT to achieve target LDL-C cholesterol levels (pounds sterling 160 for TC). The analysis demonstrates rosuvastatin is more cost-effective than the other statins in achieving UK and European cholesterol targets.

Coronary Disease↗
PubMed1996

Mechanical measurements from isolated cardiac myocytes using a pipette attachment system.

Single rat left ventricular myocytes were attached at both ends using a newly described double-barreled micropipette technique. This attachment procedure enabled the measurement of the active and passive mechanical properties of chemically skinned cells that showed little structural deformation. The force and oscillatory stiffness (100 Hz) of the cells were measured with a high signal-to-noise ratio, and the sarcomere length throughout the entire cell was monitored using image analysis. The passive properties were investigated from the resting sarcomere length to > 3 microns. Analysis of the sarcomere behavior indicated a high level of homogeneity throughout the cell. The attachment method supported the full activation of the cells by increased free Ca2+ (pCa 4.5), which produced 22.3 mN/mm (mean sarcomere length 2.11 microns). A force/pCa relationship was determined, which, when fitted according to the Hill equation, gave parameters of nH = 2.62 and pCa50 = 5.58. The described techniques allow the accurate study of the mechanical properties of single myocytes with increased fidelity and reliability over the preexisting methods.

Animals↗
PubMed1995

Nitric oxide, myocardial failure and septic shock.

Septic shock is a major cause of hospital deaths despite modern intensive therapy. Profound hypotension is caused by a collapse of regulatory mechanisms. Recent advances have established that bacterial products and the host inflammatory response together generate uncontrolled production of nitric oxide throughout the vasculature, accounting for this vasodilatation. Progressive heart failure is a further manifestation of established septic shock. Emerging research suggests that overproduction of nitric oxide within the myocardium likewise leads to loss of normal myocardial function. The possibility exists that exciting future therapies will be able to selectively inhibit the overproduction of nitric oxide and aid recovery from this frequently lethal condition.

Animals↗
PubMed1994

Effect of intense angiotensin II suppression on the diuretic response to furosemide during chronic ACE inhibition.

BACKGROUND: Contrary to expectation, most studies have demonstrated that initiation of an angiotensin-converting enzyme (ACE) inhibitor in conventional doses in patients with heart failure reduces the diuretic efficacy of furosemide. Recently, it has been suggested that single low doses (1 mg) but not high doses (25 mg) of captopril enhance furosemide-induced diuresis. It is not known whether the interaction between diuretics and ACE inhibitors are altered during long-term dosing. METHODS AND RESULTS: Eight patients with heart failure treated with diuretics and ACE inhibitors for at least 3 months were studied. All patients were established on captopril 12.5 mg three times daily for 2 weeks before the study. Sodium intake was fixed before the study, and usual medication was withheld on study days. Intravenous furosemide was given on each of 2 study days to maintain a moderate, constant diuresis. Renal plasma flow and glomerular filtration rate (GFR) were determined using clearance techniques, and urine was collected hourly over 4 hours. Captopril 12.5 mg or placebo was given in a randomized, single-blind fashion at the end of the first hour. Compared with placebo, captopril reduced plasma concentrations of angiotensin II (23 +/- 18 versus 4 +/- 3 pg/ml 1 hour after dosing, P < .02) and systolic (131 +/- 31 versus 122 +/- 29 mm Hg, P < .01) and diastolic (74 +/- 15 versus 67 +/- 13 mm Hg, P < .05) blood pressures. GFR fell (55 +/- 24 versus 51 +/- 22 mL/min, P < .02) and effective renal plasma flow rose during the first (198 +/- 76 versus 231 +/- 49 mL/min) and second hours after dosing (185 +/- 69 versus 247 +/- 74 mL/min, P < .02). Similarly, urine volumes, in response to furosemide, increased after captopril (238 +/- 90 versus 283 +/- 111 mL, P < .05, and 245 +/- 78 versus 311 +/- 92 mL, P < .01, 1 and 2 hours after dosing). Urinary electrolyte concentrations fell, but total urinary sodium (22 +/- 7 versus 28 +/- 12 mmol/hr, P < .01) and chloride (20 +/- 6 versus 25 +/- 11 mmol/hr, P < .05) excretion increased in the 2 hours after dosing, as did fractional excretion of sodium (urinary sodium/urinary creatinine) (61 +/- 27 versus 75 +/- 36 mmol/mumol, P < .01). CONCLUSIONS: Intense although transient ACE inhibition with captopril enhances the diuretic effects of furosemide during long-term ACE inhibition.

Aged↗
PubMed1993

Nitric oxide attenuates cardiac myocyte contraction.

Cardiac muscle fibers have microvessels in close proximity, the distance from the nearest capillary being no greater than 8 microns. We performed experiments on isolated, electrically stimulated, contracting guinea pig cardiac myocytes to test whether NO from endothelium or nitrovasodilators or directly superfused in solution might affect myocyte contractility. In endothelium-myocyte coculture experiments, 10(-7) M bradykinin reduced myocyte shortening by 11 +/- 3.5%. This effect was abolished in the presence of NG-nitro-L-arginine methyl ester and was unaffected by indomethacin. Sodium nitroprusside, but not organic nitrovasodilators, reduced myocyte contraction amplitude by 23% at 3 x 10(-5) M. This effect was reversed by methylene blue. Superfusion with NO solution had an effect similar to sodium nitroprusside, as did exposure to 8-bromoguanosine 3',5'-cyclic monophosphate. Thus the present study shows that cardiac myocyte contraction is attenuated by NO, which appears to act via production of guanosine 3',5'-cyclic monophosphate within the myocytes. Because cardiac myocytes in vivo are in such close proximity to endothelium, the effects of endothelial products on cardiac myocyte contractility may be important in myocardial function.

Animals↗
PubMed1992

Case report: therapeutic bronchial artery embolization in a case of Takayasu's arteritis.

The pulmonary arteries are frequently involved in Takayasu's arteritis with a reported incidence of 41-100% in affected individuals. Patients are usually asymptomatic, however, often despite extensive pulmonary involvement. We describe a patient with Takayasu's arteritis who presented with haemoptysis caused by bronchial artery hypertrophy secondary to occlusive pulmonary arterial disease, who was treated by bronchial artery embolization. This is, to our knowledge, the first reported case of haemoptysis secondary to Takayasu's arteritis successfully treated by embolization.

Adult↗