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Biomedical subjects

S G Williams

Publications and source records attributed to S G Williams.

At least 19 recordsLinked to original sources
PubMed2005

Complementary roles of simple variables, NYHA and N-BNP, in indicating aerobic capacity and severity of heart failure.

AIMS: The extent of exercise intolerance in patients with chronic heart failure (CHF) is dependent on and representative of the severity of heart failure. However, few primary care physicians have direct access to facilities for formal exercise testing. We have therefore explored whether information readily obtainable in the community can reliably predict the functional capacity of patients. METHODS AND RESULTS: Ninety-six subjects with a wide range of cardiac function (10 healthy controls and 86 CHF patients with NYHA classes I-IV, LVEF 36.9+/-15.2%) were recruited into the study and had resting plasma N-BNP and cardiopulmonary exercise testing to measure peak oxygen consumption (VO2). Significantly higher N-BNP levels were found in the CHF group (299.3 [704.8] fmol/ml, median [IQR]) compared with the healthy control group (7.2 [51.2] fmol/ml), p<0.0001. There were significant correlations between peak VO2 and N-BNP levels (R=0.64, P<0.001), peak VO2 and NYHA class (R=0.76, P=0.001), but no significant correlation was seen between peak VO2 and LVEF (R=0.0788, P=0.33). Multivariate analysis identified plasma N-BNP (P<0.0001) and NYHA class (P<0.0001) as significant independent predictors of peak VO2. Logistic modelling with NYHA class and log N-BNP to predict peak VO2<20 ml/kg/min showed that the area under the curve of receiver-operating-characteristic (ROC) curve was 0.906 (95% CI 0.844-0.968). A nomogram based on the data has been constructed to allow clinicians to estimate the likelihood of peak VO2 to be <20 ml/kg/min for given values of plasma N-BNP and NYHA class. CONCLUSIONS: By combining information from a simple objective blood test (N-BNP) and a simple scoring of functional status (NYHA), a clinician can deduce the aerobic exercise capacity and indirectly the extent of cardiac dysfunction of patients with CHF.

Adult↗
PubMed2004

From CONSENSUS to CHARM--how do ACEI and ARB produce clinical benefits in CHF?

Two decades of research from CONSENSUS to CHARM using modulators of the renin-angiotensin-aldosterone system (RAAS) in chronic heart failure (CHF) patients have shown convincing clinical benefits, but the majority of clinicians prescribing these drugs are still unclear about what mechanisms are responsible for the observed benefits. Of the candidate mechanisms hitherto proposed, there emerges a theme that best fits the spectrum of known factors from pathophysiology of heart failure to how the drugs enhance longevity of patients. This concept can be summarised as follows: after the onset of heart failure, neurohormones are activated resulting in raised levels of angiotensin, aldosterone and catecholamines, which are all known cardiotoxic agents. Cumulatively over time, they are responsible for accelerated cardiomyocyte attrition, manifesting as a faster reduction of cardiac pumping reserve, leading to worsening heart failure, more neurohormonal activation, thus propagating a vicious cycle spiralling towards an earlier fatality. The vicious cycle can be interrupted by dampening the excessive neurohormonal activities, thereby minimising cardiomyocyte losses and preserving cardiac functional reserve for longer. This culminates in maintenance of a reasonable quality of life and enhanced longevity. Such a mechanistic understanding would enable clinicians to have a better perspective on how to apply data from various clinical trials involving these drugs into clinical practice, to optimise and tailor therapy to the individual patient so that each patient can gain maximal benefits.

Angiotensin Receptor Antagonists↗
PubMed2004

The benefits of valsartan in the treatment of heart failure: results from Val-HeFT.

Angiotensin II receptor blockers (ARBs) are the most recent class of anti-hypertensive drug to enter clinical use for chronic heart failure (CHF). In the landmark Valsartan Heart Failure Trial (Val-HeFT), valsartan reduced the risk of the combined endpoint of all-cause mortality and morbidity by 13.2% over a 2-year follow-up. Although it significantly improved a pre-specified primary endpoint, it did not improve the endpoint of all-cause mortality. Valsartan administered to patients not receiving angiotensin-converting enzyme inhibitors (ACEI) at baseline reduced the endpoint of all-cause mortality by 33% and the combined endpoint of mortality and morbidity by 44%, compared with placebo. Based on these findings, valsartan became the first ARB to be approved by the US Food and Drug Administration for the treatment of New York Heart Association class II-IV HF in patients who are intolerant of ACEIs. This review provides a summary of the key Val-HeFT results and their implications in the treatment of CHF patients.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2004

Troponin T: how high is high? Relationship and differences between serum cardiac markers according to level of creatine kinase and type of myocardial infarction.

Cardiac troponins have emerged over recent years as the "gold standard" serum biochemical marker for the diagnosis and management for patients with acute myocardial infarction (MI). The relationship between old (creatine kinase; CK) and new (troponin T; TT) markers of myocardial injury were examined in this study of 392 consecutive patients admitted to a district hospital with a diagnosis of an acute MI. Significant correlation of serum TT and peak CK levels were seen (R = 0.58, p<0.0001) in all types of MI. A significant relationship was also seen according to type of MI (Q wave or non-Q wave MI) or peak CK level. The regression equation (TT (microg/l) = 0.0027 (peak CK) + 1.1160 (IU/l)) may be used by clinicians to estimate TT release from a known peak CK result and thus provide some guidance on equivalence between the two tests. Our findings provide physicians with a benchmark reference range between the two cardiac markers, according to level of peak CK.

Adult↗
PubMed2003

Does balloon mitral valvuloplasty improve cardiac function? A mechanistic investigation into impact on exercise capacity.

Procedural technical success of balloon mitral valvuloplasty (BMV) is indicated by an increase in valve area and a reduction in transvalvar gradient, but there are conflicting results regarding whether these indicators correlate with subsequent improvements in exercise capacity. We conducted a study to explore the effects of valvuloplasty on cardiac function to gain insight into the mechanisms responsible for the impact on exercise ability. Sixteen patients with mitral stenosis participated in the study and the five who did not proceed to valvuloplasty served as the control group. All patients performed maximal cardiopulmonary exercise tests before and 6 weeks after valvuloplasty (without valvuloplasty in controls). Central haemodynamics including cardiac output were measured non-invasively at rest and peak exercise. At baseline, the cardiopulmonary exercise test results were similar in the two groups. Following valvuloplasty, cardiac output did not alter at rest, but increased significantly at peak exercise (8.7+/-1.7 to 10.5+/-2.1 l min(-1), P<0.01), as did peak cardiac power output (1.88+/-0.55 to 2.28+/-0.74, P<0.05) and cardiac reserve (1.07+/-0.33 to 1.45+/-0.55 watts, P<0.05). Aerobic exercise capacity improved (13.9+/-4.2 to 16.4+/-4.3 ml kg(-1) min(-1), P<0.01) as did exercise duration (354+/-270 to 500+/-266 s, P<0.01). There were no significant changes in the controls. There was a significant correlation between the changes in peak VO(2) and changes in cardiac reserve (r=0.62, P<0.01) but not with changes in resting haemodynamics. These changes did not correlate with changes in peri-procedural mitral valve haemodynamics, despite increases in mitral valve area from 1.05+/-0.16 to 1.74+/-0.4 cm(2) (P<0.0001), accompanied by falls in the transvalvar gradient and pulmonary artery pressure (12.4+/-4.7 to 4.5+/-3 mmHg, and 26.8+/-8.4 to 17.4+/-5.2 mmHg, respectively, all P<0.0001). In conclusion, we found that successful mitral valvuloplasty in our patient cohort led to improved cardiac and physical functional capacity but not resting haemodynamics. Neither indicators of technical success nor resting haemodynamics were very reliable in predicting functional improvement.

Adult↗
PubMed2003

The effect of khat chewing on gallbladder motility in a group of volunteers.

An increase in the prevalence of gallstones has been reported from the Middle East and the Republic of Yemen. Changing dietary habits and obesity are thought to be responsible but other local factors may contribute such as chewing the leaves of the khat plant (Catha edulis Forsk.) which is a widespread social custom in Yemen. We have studied the effects of khat chewing on gallbladder motility in a group of 10 healthy volunteers. All subjects underwent ultrasound measurements of gallbladder volume after chewing khat leaves or lettuce, which was used as the control. Results were compared after chewing for up to 2h in the fasting state and in response to a fatty meal. There was no significant change in gallbladder volume after chewing khat compared with lettuce in the fasting state (P=0.7) or in gallbladder emptying after a fatty meal (P=0.4) and we conclude that khat chewing has no clinically significant effect on gallbladder motility.

Adult↗
PubMed2003

Open access echocardiography: a prospective audit of referral patterns from primary care.

Following recently published recommendations and guidelines, a prospective audit of 222 consecutive patients referred for open access echocardiography was conducted over a period of three months in a large district general hospital in the UK. Our study demonstrated the waiting time for an open access echocardiogram to be shorter than the waiting time for the outpatient clinic, which allowed identification of clinically significant cardiac disease sooner, leading to early advice on patient management. Specialist referral was avoided by the inclusion of management comments by a cardiologist in the technical echocardiogram report. We showed that open access echocardiography for detection of left ventricular systolic function, should be performed only if the ECG is abnormal, confirming previous reports. ECG interpretation in primary care is unreliable. In view of limited resources, hospitals should vigorously screen referrals for open access echocardiography.

Atrial Fibrillation↗
PubMed2002

Artificial urinary sphincter implantation in the irradiated patient: safety, efficacy and satisfaction.

OBJECTIVE: To compare the long-term outcome of artificial urinary sphincter (AUS) implantation in patients after prostatectomy, with and with no history of previous irradiation. PATIENTS AND METHODS: The study included 98 men (mean age 68 years) with urinary incontinence after prostatectomy for prostate cancer (85 radical, 13 transurethral resection) who had an AUS implanted. Twenty-two of the patients had received adjuvant external beam irradiation before AUS implantation. Over a mean (range) follow-up of 46 (5-118) months, the complication and surgical revision rates were recorded and compared between irradiated and unirradiated patients. The two groups were also compared for the resolution of incontinence and satisfaction, assessed using a questionnaire. RESULTS: Overall, surgical revision was equally common in irradiated (36%) and unirradiated (24%) patients. After activating the AUS, urethral atrophy, infection and erosion requiring surgical revision were more common in irradiated patients (41% vs. 11%; P < 0.05); 70% of patients reported a significant improvement in continence, regardless of previous irradiation. Patient satisfaction remained high, with > 80% of patients stating that they would undergo surgery again and/or recommend it to others, despite previous irradiation and/or the need for surgical revision. CONCLUSIONS: Despite higher complication and surgical revision rates in patients who have an AUS implanted and have a history of previous irradiation, the long-term continence and patient satisfaction appear not to be adversely affected.

Aged↗
PubMed2002

A mechanistic investigation of ACE inhibitor dose effects on aerobic exercise capacity in heart failure patients.

BACKGROUND: Angiotensin converting enzyme inhibitors at high doses have been shown to improve prognosis of heart failure patients. Their beneficial effects on exercise capacity have been less convincing in large parallel group studies. The objective of this investigation was to explore the mechanisms involved in dose-related functional effects and to test the hypothesis that a trial recommended high dose of lisinopril would improve aerobic exercise capacity and cardiovascular function more than with a low dose. METHODS: Twelve patients with symptomatic heart failure completed a randomized double-blind crossover trial of lisinopril 5 mg o.d. and 20 mg o.d. for 24 weeks, crossing over the doses at 12 weeks. The primary end-point was aerobic exercise capacity, and the secondary end-points were cardiac performance at peak exercise and dobutamine stimulation. RESULTS: The aerobic exercise capacity (primary end-point) was significantly higher during the 5mg per day dosage compared to the 20 mg (1696 vs 1578 ml.min(-1), P=0.016), equivalent to a rise of 1.53 ml.kg(-1)min(-1) from the 19.6 ml.kg(-1)min(-1) with 20mg when normalized by body weight. Seventy-three percent of patients showed greater peak oxygen consumption and peak cardiac power output with the 5mg per day dose than the 20 mg, and none showed the opposite. In terms of cardiac performance, although the results were not statistically significant, there was a consistent pattern showing the same directional changes in favour of the lower dose in peak exercise cardiac power output and cardiac power output at maximal dobutamine. There were no significant differences in the resting values. A total of 24 adverse reactions were reported during the 5 mg phase compared to 38 during the 20 mg phase. CONCLUSIONS: Contrary to expectation, the aerobic exercise capacity of patients was found to be greater with the lower dose of lisinopril, suggesting that therapy with ACE inhibitors for heart failure may require tailoring the doses to the individual to optimize functional benefits in relation to the assumed prognostic benefits.

Aged↗
PubMed2001

Escherichia coli strains that allow antibiotic-free plasmid selection and maintenance by repressor titration.

We report the construction of two novel Escherichia coli strains (DH1lacdapD and DH1lacP2dapD) that facilitate the antibiotic-free selection and stable maintenance of recombinant plasmids in complex media. They contain the essential chromosomal gene, dapD, under the control of the lac operator/promoter. Unless supplemented with IPTG (which induces expression of dapD) or DAP, these cells lyse. However, when the strains are transformed with a multicopy plasmid containing the lac operator, the operator competitively titrates the LacI repressor and allows expression of dapD from the lac promoter. Thus transformants can be isolated and propagated simply by their ability to grow on any medium by repressor titration selection. No antibiotic resistance genes or other protein expressing sequences are required on the plasmid, and antibiotics are not necessary for plasmid selection, making these strains a valuable tool for therapeutic DNA and recombinant protein production. We describe the construction of these strains and demonstrate plasmid selection and maintenance by repressor titration, using the new pORT plasmid vectors designed to facilitate recombinant DNA exploitation.

Amino Acid Sequence↗
PubMed2001

Left ventricular volume reduction without ventriculectomy.

Partial left ventriculectomy (the Batista procedure) to achieve left ventricular volume reduction (LVVR) has been advocated as an alternative to cardiac transplantation in patients with end-stage dilated left ventricles. Here, we describe a new technique of LVVR that uses realignment of the papillary muscles, thus avoiding ventriculectomy, and report preliminary results. Eight patients (all male, mean age 49.3 [range 38 to 70] years) underwent LVVR between October 1998 and March 2000 as an adjunct to surgical coronary revascularization. Five were assessed with echocardiography and cardiopulmonary exercise testing before and after (mean follow-up time 267 [range 94 to 416] days) the operation. LVVR significantly improved left ventricular end-diastolic volume (254 +/- 32 to 218 +/- 36 mL, p = 0.03), left ventricular ejection fraction (20.14% +/- 1.36% to 31.28% +/- 2.32%, p = 0.007), and exercise duration (from 394 +/- 88 to 611 +/- 79 seconds, p = 0.03). A nonsignificant improvement in maximal oxygen consumption was also observed. This technique of LVVR is relatively simple to perform and is accomplished through a small apical cardiotomy. Preliminary results show an encouraging functional improvement following surgery. Future controlled studies are required to assess this novel technique further.

Adult↗
PubMed2001

Disparate results of ACE inhibitor dosage on exercise capacity in heart failure: a reappraisal of vasodilator therapy and study design.

Despite manifest benefits of angiotensin converting enzyme (ACE) inhibitors on the prognosis of patients with heart failure, there is a lack of consistency in the results of trials investigating the effects of ACE inhibitors on exercise capacity. The inconsistencies cannot be readily explained by variations in effects on known neurohumoral or conventional haemodynamic factors. Drawing on insights from physiology of pump-load interactions, in a normal circulation there is an optimal extent of systemic vasodilation at which the delivery of hydraulic energy from the cardiac pump is maximal (the 'impedance matchpoint'). In heart failure, the vasoconstrictive effects shift the operating point towards mismatch at higher resistances, and optimal vasodilatory therapy would reshift the operating point to the matchpoint. Excessive dosage, however, would cause overvasodilatation leading to a reduction in cardiac power output and consequently compromising exercise ability. High levels of ACE inhibitors may not therefore improve exercise ability. Another potential reason for the observed inconsistencies is that the often used parallel-group study design (ideal for mortality studies) may not be suitable for investigating drug effects on exercise capacity because dropouts from such studies would introduce occult selection biases, thereby confounding treatment effects. In conclusion, this reappraisal of the conflicting observations reported on ACE inhibitor effects on exercise capacity has highlighted a proposition that there is an optimal dosage of ACE inhibitors which will most enhance exercise capacity, and this will require further well designed cross-over studies to elucidate.

Angiotensin-Converting Enzyme Inhibitors↗