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Biomedical subjects

A C Keech

Publications and source records attributed to A C Keech.

15 recordsLinked to original sources
PubMed2005

Urinary albumin levels in the normal range determine arterial wall thickness in adults with Type 2 diabetes: a FIELD substudy.

AIM: Cardiovascular disease (CVD) rates are substantially higher among patients with Type 2 diabetes than in the general population. The objective of this study was to identify the determinants of carotid intima media thickness (IMT) in patients with Type 2 diabetes. METHODS: We measured the thickness of the intima media layer of the carotid artery, a strong predictor of the risk of future vascular events, in 397 Type 2 diabetic patients drawn from the Fenofibrate Intervention and Event Lowering in Diabetes study, prior to treatment allocation. RESULTS: The mean IMT was 0.78 mm [interquartile range (IQR) 0.23 mm], and the maximum IMT was 1.17 mm (IQR 0.36 mm). By multivariate analysis, age, sex, duration of diabetes, triglycerides, and total cholesterol were independently correlated with IMT, as was urine albumin-creatinine ratio (ACR) (P < 0.001). The effect of ACR on IMT was further examined by tertile. Clinically significant differences in IMT were associated with ACR > 0.65 mg/mmol, approximately one-fifth the standard clinical threshold for microalbuminuria (P < 0.01). Long-term diabetes, independent of other parameters, was associated with a 50% increase in age-related thickening. CONCLUSIONS: IMT in people with Type 2 diabetes is independently and continuously related to urine albumin levels and to the duration of diabetes. These results support previous data linking urine albumin measurements within the normal range with increased ischaemic cardiac mortality in the setting of Type 2 diabetes, and strongly suggest that urine albumin levels within this range should trigger a formal evaluation for CVD.

Aged↗
PubMed2001

Asia-Pacific collaboration on coronary heart disease risk factor intervention: study design and methods.

BACKGROUND: Age-adjusted death rates for coronary heart disease (CHD) have been decreasing in populations of developed countries. At the same time, CHD in the Asia-Pacific region appears to be increasing in parallel with the 'Westernisation' of diet and lifestyle. More epidemiological information is needed from the Asia-Pacific region in order to be able to predict trends in CHD and to plan resources for treatment. In this paper we outline the study design of a survey of coronary heart disease risk factors in Asia-Pacific countries. AIMS: To ascertain and compare in 10 countries: (i) rates of measurement of risk factors; (ii) levels of risk factors, and (iii) management of risk factors. METHODS: A retrospective survey was conducted in 180 randomly selected hospitals using a population-weighted sampling frame. Participating countries were Australia, Indonesia, Japan, Korea, Malaysia, New Zealand, the Philippines, Singapore, Taiwan and Thailand. Data covered a 6-month period from the patient's admission to hospital with myocardial infarction or unstable angina. Data included measures of hypertension, smoking, obesity, diabetes, dyslipidaemia and family history of coronary disease. The study design incorporated rigorous quality-assurance methods to ensure reliability. CONCLUSIONS: The study will provide data comparable to those from studies in Europe and the USA. Together, these studies will provide an international perspective on coronary risk factors.

Journal Article↗
PubMed1997

Hemorrhagic complications of intravenous heparin use.

To document the incidence of bleeding complications occurring in patients admitted to a cardiology service treated with intravenous heparin and to identify the major risk factors for these adverse events. Intravenous heparin is effective treatment for a variety of cardiologic conditions but is associated with a number of adverse effects, including hemorrhage. During the study, 1,253 consecutive patients were admitted for acute cardiac care and of these, 416 were treated with intravenous heparin. A total of 39 complications occurred in 37 heparin-treated patients (8.9%), of which 23 were hemorrhagic complications occurring in 21 heparin-treated patients (5.5%). Of these hemorrhagic complications, 12 were directly related to a vascular access site and 11 were apparently "spontaneous" hemorrhages. There was no apparent relation between the dose (mean 1,021 U/hour [range 531 to 1,882]) or duration (6.7 +/- 5.7 days) of heparin therapy and hemorrhagic complications. In a multivariate analysis, female gender (odds ratio [OR] 4.76 [14.39 to 1.56]; p = 0.006), recent thrombolytic therapy (OR 12.9 [4.1 to 40.6]; p <0.0001), and a reduced admission hemoglobin (OR 1.41 [0.52 to 0.97]; p = 0.031) were significantly predictive of a hemorrhagic event. The incidence of cardiac catheterization procedures was not significantly higher in the complication group (OR 3.9 [0.84 to 18.4]; p = 0.082). Aspirin therapy, admission platelet count, and weight were noncontributory. Hemorrhagic complications occurred in 5.5% of patients receiving a continuous infusion of heparin. The use of thrombolytic therapy, female gender (independent of weight), and a reduced admission hemoglobin were significant independent predictors of hemorrhagic events.

Aged↗
PubMed1996

Absence of effects of prolonged simvastatin therapy on nocturnal sleep in a large randomized placebo-controlled study. Oxford Cholesterol Study Group.

1. It has been suggested that lipophilic HMG CoA reductase inhibitors, like lovastatin and simvastatin, may cause sleep disturbance. 2. Six hundred and twenty-one patients at increased risk of coronary heart disease were randomized in a single centre to receive 40 mg daily simvastatin, 20 mg daily simvastatin or matching placebo. To assess the effects of prolonged use of simvastatin on nocturnal sleep quality and duration, a sleep questionnaire was administered to 567 patients (95% of 595 survivors) at an average of 88 weeks (range: 44-129 weeks) after randomization. 3. The main outcome measures were sleep-related problems and use of sleep-enhancing medications reported during routine study follow-up visits, and responses to the sleep questionnaire about changes in sleep duration and about various sleep events during the preceding month. 4. No differences were observed between the treatment groups in the frequency of sleep-related problems reported, in the proportion of follow-up visits at which such problems were reported, or in the use of sleep-enhancing medications. The numbers who stopped study treatment were similar in the different treatment groups, and no patient stopped principally because of insomnia. In response to the sleep questionnaire, there were no significant differences between the treatment groups in reports of various sleep events during the preceding month, except that slightly fewer patients allocated simvastatin reported waking often. No differences in sleep duration were observed. 5. This placebo-controlled trial does not indicate any adverse effects of prolonged treatment with simvastatin on systematically sought measures of sleep disturbance.

Adult↗
PubMed1996

Hormone replacement therapy is associated with improved arterial physiology in healthy post-menopausal women.

OBJECTIVE: Oestrogen replacement therapy is associated with a marked reduction in coronary event rates in post-menopausal women. As older age is associated with progressive arterial endothelial damage, a key event in atherosclerosis, we assessed whether hormone replacement therapy (HRT) with oestrogen alone, or oestrogen and progesterone combined, is associated with improved endothelial function in healthy women after the menopause. DESIGN: Using high resolution external vascular ultrasound, brachial artery diameter was measured at rest and in response to reactive hyperaemia, with increased flow causing endothelium-dependent dilatation (flow-mediated dilatation). PATIENTS: We investigated 135 healthy women; 40 were pre-menopausal (mean +/- SD age/26 +/- 6 years, group 1), 40 were post-menopausal and had never taken HRT (aged 58 +/- 3 years; group 2) and 55 were age-matched post-menopausal women who had taken HRT for > or = 2 years, from within 2 years of the menopause (aged 57 +/- 4 years; group 3). In group 3, 40 women were on combined oestrogen and progesterone and 15 on oestrogen-only HRT. RESULTS: In group 2, flow-mediated dilatation was significantly reduced compared with group 1 (4.4 +/- 3.4 vs 9.6 +/- 3.6%, P < 0.001), consistent with a decline in arterial endothelial function after the menopause. In group 3, however, flow-mediated dilatation was significantly better than group 2 (6.2 +/- 3.3 vs 4.4 +/- 3.4%, P = 0.01), suggesting a protective effect of HRT. Flow-mediated dilatation was similar in women taking oestrogen alone and in those on combined HRT (5.5 +/- 2.8 vs 6.5 +/- 3.4%, P = 0.40). CONCLUSIONS: Long-term HRT is associated with improved arterial endothelial function in healthy post-menopausal women. This benefit was observed in both the combined hormone replacement and unopposed oestrogen therapy groups. This may explain some of the apparent cardioprotective effect of HRT after the menopause.

Adolescent↗
PubMed1995

Absence of effect of simvastatin on the progression of lens opacities in a randomised placebo controlled study. Oxford Cholesterol Study Group.

AIMS: A detailed assessment of ophthalmic effects of an HMG CoA reductase inhibitor, simvastatin, was performed. METHODS: Six hundred and twenty one individuals considered to be at increased risk of coronary heart disease were randomised, following an 8 week placebo 'run in' period, to receive 40 mg daily simvastatin, 20 mg daily simvastatin, or matching placebo. Patients with a baseline corrected visual acuity better than 6/24 and without a history of cataract were eligible for detailed ophthalmic assessment at 6 months (539 patients assessed) and at 18 months (474 patients assessed). RESULTS: No significant differences between the treatment groups were detected at the 6 month or 18 month visit in the refractive condition of the eye or in the mean intraocular pressure. Nor were there clear differences in the Oxford grading system scores for various measures of the major types of cataract (cortical spokes, posterior subcapsular cataract, nuclear brunescence, white scatter) or for other morphological features visible within the lens (fibre folds or focal dots). Scheimpflug slit image photographs and retroillumination analysis of the percentage of cataract within a defined region of the lens were also performed at each visit, with no clear differences observed between the treatment groups. CONCLUSION: This single centre double blind study found no good evidence of any adverse effects of 18 months of simvastatin treatment on lens opacity formation, using a variety of validated techniques to assess cataract development. Routine clinic follow up of visual symptoms and admission to hospital for ophthalmic procedures over 5 years of treatment was also reassuring, with no excess adverse outcomes observed with simvastatin.

Adult↗
PubMed1989

Absorption and elimination of bismuth from oral doses of tripotassium dicitrato bismuthate.

The pharmacokinetics of bismuth subcitrate were studied in plasma and urine under conditions of single and multiple dosing (28-56 days) using atomic absorption technique. Single dose plasma pharmacokinetics showed peak concentrations of 5.5-57.5 micrograms.l-1 (mean = 24.7 micrograms.l-1), reached between 30 and 60 min post dosing with an apparent biphasic elimination pattern. Multiple dose studies showed a continuing rise in plasma concentration and urine excretion rate reaching apparent steady-state levels over 7-29 days (mean = 18 days). Washout studies in 6 individuals reciprocated accumulation. Maximum equilibrated plasma levels of 7.6-58.3 micrograms.l-1 (mean = 38.3 micrograms.l-1) were well below those associated with encephalopathy. The half-life of bismuth elimination was 20.7 days. Present patterns of intermittent dosing with bismuth are unlikely to be associated with bismuth accumulation despite slow accumulation and elimination.

Adult↗
PubMed1988

Extent and pharmacokinetic mechanisms of oral atenolol-verapamil interaction in man.

Chronic coadministration of oral verapamil with oral atenolol resulted in a variable increase in atenolol steady-state plasma concentrations in a group of 10 patients on chronic maintenance therapy. Individual subjects showed changes in area under the plasma atenolol concentration-time curve (AUC) of more than 100%, however group comparisons did not achieve statistical significance unless normalized for verapamil dose. Renal clearance of atenolol was shown to be decreased by more than 25% in 2 subjects studied using intravenous dosing of atenolol. This interaction is likely to contribute to the documented clinical intolerance of combinations of atenolol and verapamil.

Administration, Oral↗