Biomedical subjects
Publications and source records attributed to C J Knight.
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OBJECTIVES: Although it only occurs in a minority of patients, renal involvement is a life-threatening complication of scleroderma (SSc). We have investigated the utility of two formulae to calculate glomerular filtration rate (GFR) in a population of SSc patients. METHODS: Twenty-six patients (20 female, 6 male, median age 58 yr, age range 12-80 yr) satisfied our criteria for inclusion in a retrospective comparison of measured and calculated GFR. GFR was measured using (51)Cr-EDTA. The modified Cockcroft and Gault formula and equation 7 from the Modification of Diet in Renal Disease (MDRD) were used to calculate GFR. RESULTS: Eighteen out of 19 patients analysed with a serum creatinine concentration less than the upper limit of the normal range had a measured GFR outside the normal range. Three patients with a normal creatinine concentration had a measured GFR <60 ml/min and in each of these the calculated GFR was also abnormal. All patients with a measured GFR <60 ml/min were identified using both the MDRD and the modified Cockcroft and Gault formula to calculate GFR. The greatest correlation between measured and calculated GFR was seen when the MDRD formula, which employs demographic and serum variables, was used in patients with body surface area (BSA) >1.4 m(2) who were not taking Iloprost (r=0.91). Use of the Cockcroft and Gault formula to calculate creatinine clearance with a correction factor for GFR, the inclusion of patients taking Iloprost and the inclusion of patients with BSA <1.4 m(2) were all associated with a lower degree of correlation. CONCLUSION: Serum creatinine is a poor marker of renal function in SSc patients. Calculating GFR from demographic and serum variables is a simple technique to identify SSc patients who have abnormal renal function. The authors recommend the use of the MDRD formula.
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AIMS: Coronary stent deployment is a major advance in percutaneous treatment of ischaemic heart disease, but 10-40% of patients still develop angiographic restenosis by 6 months due to neointimal hyperplasia. Patient-specific factors, including genetic factors, can contribute to this process. We have conducted a prospective study to examine the involvement of genetic risk factors (eNOS, ACE, MMP-3, IL-6, and PECAM-1) in restenosis following coronary stent deployment. METHODS AND RESULTS: A total of 226 patients who underwent elective and successful coronary artery stenting to de novo lesions in native coronary arteries were studied. Two hundred and five (90.7%) patients were restudied by coronary angiogram at 6 months and the stented lesions were assessed using an automated quantitative angiography system. Genotype was determined by polymerase chain reaction (PCR) and restriction enzyme digestion. Restenosis rate, defined as >or=50% diameter stenosis, was 29.3%. The overall genotype frequency distributions were in Hardy-Weinberg equilibrium for all variants. Carriers of the 298Asp allele of the eNOS Glu298Asp polymorphism showed a higher frequency of restenosis with an odds ratio of 1.88 (95%CI: 1.01-3.51, P=0.043) compared to 298Glu homozygotes. Carriers of the -786C allele of the eNOS -786T>C polymorphism also showed a higher frequency of restenosis with odds ratio of 2.06 (95%CI: 1.08-3.94, P=0.028). These effects were essentially additive and were independent of other classical risk factors. Other studied genes did not show significant association with coronary in-stent restenosis. CONCLUSION: In patients with coronary artery disease, the possession of the 298Asp and -786C variants of the eNOS gene are a risk factor for coronary in-stent restenosis, demonstrating the importance of the nitric oxide system in restenosis.
OBJECTIVE: To evaluate biomechanical properties of skin in patients with systemic sclerosis (SSc) using the BTC-2000 suction device. METHODS: Twenty five patients with limited cutaneous SSc (lcSSc), 20 patients with diffuse disease (dcSSc), and 25 age matched healthy controls were evaluated. Viscoelastic deformation (VED, mm), elastic deformation (ED, mm), ultimate deformation (UD, mm), and pressure-deformation ratio (PDR, mm Hg/mm) were measured on the dorsal surface of the forearm, shoulder, and above the trapezius muscle on the back. RESULTS: Indices of skin extensibility (VED, ED, UD) were reduced and resistance to stress (PDR) increased in patients with dcSSc compared with healthy controls, or patients with lcSSc, at all three sites (p<0.001). At all sites, and overall, UD, ED, and VED were lower and PDR was higher at skin score above grade 2, compared with clinically normal skin. For both lcSSc and dcSSc biomechanical differences from controls were found even at sites of clinically normal skin. CONCLUSION: BTC-2000 is a sensitive tool for clinical evaluation of skin involvement in SSc and may be a valuable adjunct to skin sclerosis score in disease monitoring.
OBJECTIVE: To establish why recurrent myocardial ischaemia predicts adverse outcome in patients with refractory unstable angina on maximal medical treatment. DESIGN: Prospective observational study in 101 patients with refractory unstable angina who underwent continuous ST-segment monitoring and kept detailed pain charts prior to cardiac catheterization. Setting Tertiary referral centre. RESULTS: Significant coronary disease was identified in 90 subjects with 74 (82%) having multivessel disease, 41 (46%) complex lesion morphology, and 10 (11%) subjects with definite features of intra-coronary thrombus. The frequency of complex lesions or intra-coronary thrombus did not differ in relation to the extent of coronary disease. Recurrent chest pain was present in 72 of the 90 (80%) subjects, while transient ischaemia was detected in 26 (29%). The presence of transient ischaemia was a powerful predictor of complex lesions or thrombus (odds ratio 7.1;P<0.001). Subjects with severe recurrent chest pain had a greater frequency of intracoronary thrombus (odds ratio 9.5;P<0.05). CONCLUSIONS: In unstable angina once the normal mechanisms causing myocardial ischaemia (i.e. increased myocardial demand and coronary vasoconstriction) have been treated using maximal antianginal treatment, the continued development of transient myocardial ischaemia is strongly associated with complex coronary lesion morphology and intracoronary thrombus. It is already known that patients with complex lesion morphology and intracoronary thrombus have an adverse outcome in unstable angina and therefore it is this association that explains why transient ischaemia is a predictor of poor outcome in unstable angina.
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Hypertrophic cardiomyopathy is a familial cardiac disorder with heterogeneous expression and a diversity of morphological, functional and clinical features. Some individuals with hypertrophic cardiomyopathy may be asymptomatic while others are disabled by symptoms of angina and breathlessness. This article summarizes the genetics, pathophysiology and present management of this important condition.
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AIMS: The GPIIb-IIIa complex on the platelet membrane plays an important part in thrombosis as it is the receptor for fibrinogen. The gene for platelet membrane glyco-protein IIIa has multiple alleles one of which, the GPIIIa-Proline33 (HPA-1b, PlA2, Zwb) allele has been reported in some, but not all studies, to be associated with an increased risk of myocardial infarction. We investigated whether the presence of the Pro33 form of GPIIIa on the platelet membrane is associated with increased fibrinogen binding. METHODS AND RESULTS: Blood samples from 70 patients (54 male) with stable angina of whom 22 (18 male) had a history of previous myocardial infarction, were analysed for the GPIIIa-Leu-Pro33 polymorphism at the genomic level, and for whole blood flow cytometric measurement of platelet fibrinogen binding. The GPIIIa-Pro33 form was present in 20 (28.6%) patients (1 homozygous) representing an allele frequency of 0.85 and 0.15 (GPIIIa-Leu33:Pro33). The incidence of myocardial infarction was higher (40.0%) in patients positive for GPIIIa-Pro33 than in those without (32.0%) but this was not significant (P=0.58). Fibrinogen binding to ADP-stimulated platelets was significantly higher in the GPIIIa-Pro33 positive group at all ADP concentrations (<0.0001; two way ANOVA). There was no association between fibrinogen binding and the level of expression of the GPIIb-IIIa complex, platelet volume or platelet count. Fibrinogen binding in response to thrombin stimulation was not different between the groups (P>0.05). CONCLUSIONS: The increased tendency of platelets from patients with the Pro33 form of GPIIIa may predispose patients with this allele to a higher risk of acute thrombotic events, and argues for selective use of therapeutic agents that inhibit ADP-mediated platelet activation in occlusive vascular disease states.
BACKGROUND: Primary intracoronary stenting reduces the rate of restenosis when compared with balloon angioplasty (PTCA) in selected patients. The strategy of PTCA followed by provisional stent placement for suboptimal PTCA results may be preferable to universal stenting but has not yet been tested in a randomized trial. METHODS: An attempt was made to obtain an optimal result with PTCA alone in 143 patients. Stenting was required in 50 patients (35%) for significant coronary dissection or PTCA failure. In the remaining 93 patients, the angiographic result was assessed immediately using on-line quantitative coronary angiography and classified as either optimal (<15% residual stenosis) or suboptimal (>/=15% residual stenosis). Sixteen patients (11%) had an optimal result from PTCA. The remaining 77 (54%) patients had a suboptimal result and were immediately randomized either to no further treatment or to the placement of a stent. The primary end-point was the rate of restenosis (>50% stenosis), assessed by quantitative coronary angiography, at 6 months. RESULTS: Angiographic follow-up was completed in 132 patients. Restenosis occurred in 53 (36,69)% of patients with a suboptimal result randomized to PTCA alone compared with 24 (12,41)% of patients randomized to stent (P=0.023). There was no significant difference in minimal luminal diameter at follow-up between the randomized groups. The rate of restenosis was 14 (2,43)% in patients with an optimal PTCA result and 14 (5,28)% in those that required stenting. CONCLUSIONS: Optimal angiographic results following conventional PTCA are rare and the restenosis rate following suboptimal results is high. The strategy of stenting suboptimal results is associated with a significant reduction in the rate of stenosis.
The aims of this study were to evaluate the simultaneous assessment of myocardial viability and function for the detection of hibernating myocardium using ECG-gated 99Tcm-tetrofosmin single photon emission tomography (SPET), and to compare the technique with 201Tl SPET in combination with cine magnetic resonance imaging (MRI). Fifteen patients aged 41-70 years with impaired left ventricular function (mean LVEF 23.4 +/- 8.1%) and three-vessel coronary artery disease were studied before and after coronary artery bypass grafting (CABG). The following investigations were performed within the 3 months before surgery: stress/redistribution and separate-day rest 201Tl SPET with early and late imaging, stress and ECG-gated rest 99Tcm-tetrofosmin SPET, and resting cine MRI. Between 3 and 6 months post-surgery, stress/redistribution 201Tl SPET and cine MRI were repeated. Tracer uptake in nine segments of the left ventricle was graded visually and by quantitative analysis. Myocardial motion and thickening were graded visually from cine MRI and from gated 99Tcm-tetrofosmin SPET images. Segments were defined as hibernating pre-operatively if tracer uptake was moderately reduced or better but myocardial motion was severely hypokinetic or worse. The accuracy of pre-operative assessment was assessed by comparison with post-operative function assessed by MRI. The sensitivity and specificity for the prediction of functional improvement were 69% and 60% for late rest 201Tl uptake combined with MRI; 58% and 62% for rest 99Tcm-tetrofosmin uptake combined with MRI; and 62% and 45% when gated 99Tcm-tetrofosmin SPET was used to assess both tracer uptake and wall motion. In 21 of 135 segments, contractile function could not be assessed by gated 99Tcm-tetrofosmin SPET because of inadequate tracer uptake; function was improved in 5 (25%) of these segments after CABG. In conclusion, the combined assessment of viability and function using ECG-gated 99Tcm-tetrofosmin SPET is feasible and it allows the assessment of hibernating myocardium with similar accuracy to the combination of ungated 99Tcm-tetrofosmin SPET with MRI. Where tracer uptake is too poor for assessment of function, there is a low incidence of myocardial hibernation. However, ECG-gated 99Tcm-tetrofosmin SPET is not superior to 201Tl SPET combined with cine MRI in the identification of hibernation.
BACKGROUND: Both radionuclide perfusion tracers and contractile response to dobutamine have been used to identify hibernating myocardium. The aim was to compare 201Tl (thallium) single photon emission CT (SPECT), 99mTc-tetrofosmin (tetrofosmin) SPECT, and dobutamine cine MRI for identifying regions of reversible myocardial dysfunction. METHODS AND RESULTS: Thirty patients with 3-vessel coronary artery disease and impaired left ventricular function (mean LVEF, 24.0%; SD, 8.3%) scheduled for coronary bypass grafting were recruited. All underwent rest/dobutamine stress (5 to 10 microg . kg-1 . min-1) cine MRI, stress/rest tetrofosmin SPECT, and stress/redistribution and separate-day rest/redistribution thallium SPECT before surgery. Stress/redistribution thallium SPECT and resting MRI were repeated after surgery. In a 9-segment model, SPECT images were scored visually for tracer uptake, which was also measured from a polar plot of myocardial counts. MRI was scored visually for endocardial motion, myocardial thickening, and thickness. Five patients died before follow-up, and 2 declined postoperative investigation. In the remaining 23 patients, mean LVEF increased from 24.0% (SD, 8.3%) to 29.7% (SD, 11.1%) (P<0.05). Of 207 segments analyzed, 145 had significantly abnormal wall motion before surgery, and 82 of these improved function after revascularization. The criteria for predicting recovery of severely hypokinetic segments on preoperative imaging were tracer uptake graded "moderately reduced" or better, or positive inotropic response on dobutamine MRI. Late-rest thallium images showed the highest sensitivity (76%), compared with stress-redistribution thallium (68%) and rest tetrofosmin (66%) (P<0.05). All 3 tracer techniques were nonspecific (44%, 51%, and 49%, respectively). Redistribution of thallium after the resting injection was insensitive (18%) but highly specific (83%). Inotropic response to dobutamine was also insensitive (50%) but specific (81%). CONCLUSIONS: Radionuclide uptake is a sensitive but nonspecific predictor of myocardial functional recovery, whereas dobutamine MRI is specific but insensitive.
The antianginal efficacy and tolerability of amlodipine and diltiazem were compared in a double-blind randomized trial of 97 patients with angina resistant to atenolol alone. Both amlodipine and diltiazem significantly reduced the frequency of angina attacks (p <0.001) and glyceryl trinitrate consumption (p <0.05 to p <0.01). During Holter monitoring, both treatments reduced the overall frequency of ambulatory myocardial ischemia, although changes did not reach statistical significance. Exercise test parameters (total exercise time, time to angina, time to ST depression, and maximum ST depression) tended to improve with both treatments, but changes did not achieve statistical significance relative to baseline or to each other. Both drugs were generally well tolerated. Adverse events occurred in 15 patients in the amlodipine group (30%) and in 17 patients in the diltiazem group (36%), but patients taking diltiazem reported almost twice as many adverse events (30) patients taking amlodipine (18). Quality of life, as assessed by total Nottingham Health Profile Scores, was not significantly different between treatments. The addition of either once-daily amlodipine or twice-daily sustained release diltiazem improved symptoms in patients with angina resistant to atenolol alone, but diltiazem was associated with more frequent and more serious adverse events.
AIMS: To assess the ability of clinical characteristics, admission ECG and continuous ST segment monitoring in determining long-term prognosis in unstable angina. METHODS: Two hundred and twelve patients with unstable angina (mean age 59 years), presenting within 24 h of an acute episode of angina were recruited at three hospitals and treated with standardized medical therapy. All patients kept chest pain charts and underwent ST segment monitoring for 48 h. The occurrence of death, myocardial infarction, and need for revascularization was assessed over a median follow-up of 2.6 years. RESULTS: The risk of death of myocardial infarction was greatest in the first 6-8 weeks after admission. Admission ECG ST depression and the presence of transient ischaemia predicted increased risk of subsequent death or myocardial infarction, whereas a normal ECG predicted a good prognosis. In 14 patients, ST segment monitoring provided the only evidence of recurrent ischaemia, and 72% of this group suffered an adverse event. Transient ischaemia and a history of hypertension were the most powerful independent predictors of death or myocardial infarction. CONCLUSIONS: Adverse events in unstable angina occur early after admission and can be predicted by clinical and ECG characteristics, and by the presence of transient ischaemia during ST segment monitoring. Risk stratification by these simple assessments can identify patients with unstable angina at high risk.