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Biomedical subjects

P G Mills

Publications and source records attributed to P G Mills.

At least 19 recordsLinked to original sources
PubMed1997

The role of signal averaged P wave duration and serum magnesium as a combined predictor of atrial fibrillation after elective coronary artery bypass surgery.

OBJECTIVE: To investigate the role of low serum magnesium as a trigger for atrial fibrillation in patients with a substrate for the arrhythmia (assessed by signal averaged P wave duration). DESIGN: A case-control study. SETTING: A regional referral cardiac centre. PATIENTS AND INTERVENTIONS: 105 consecutive patients undergoing elective coronary artery bypass surgery had signal averaged P wave recordings before operation. Serum electrolytes were analysed preoperatively and on days 1, 2, and 5 after surgery. MAIN OUTCOME MEASURES: Any episode of electrocardiographically recorded atrial fibrillation was taken as a study end point. RESULTS: Of 102 patients discharged, 27 (26%) had documented episodes of atrial fibrillation at a mean of 2.7 days after surgery. A combination of P wave duration > 155 ms and serum magnesium on the first postoperative day of < 0.7 mmol/l had a sensitivity of 75% and specificity of 80% for predicting atrial fibrillation. Duration of hospital stay (7.9 v 6.8 days) was longer in the atrial fibrillation group (P < 0.01). Stepwise regression showed age, serum magnesium < 0.7 mmol/l on the first postoperative day (both P < 0.001), angiotensin converting enzyme inhibitor withdrawal (P < 0.02), and signal averaged P wave duration (P = 0.04) to be independent predictors. CONCLUSIONS: The combination of signal averaged P wave duration and low serum magnesium on the first postoperative day identified the majority of patients with atrial fibrillation after coronary artery bypass surgery. Early identification and pharmacological treatment for selected patients may reduce the incidence of postoperative atrial fibrillation.

Aged↗
PubMed1996

Modified low density lipoprotein and cytokines mediate monocyte adhesion to smooth muscle cells.

Monocyte adhesion to the arterial wall is a key event in the atherosclerotic process. We studied the interactions between human coronary arterial intimal smooth muscle cells (SMCs) and monocytes by examining (i) whether SMCs mediate monocyte adhesion when stimulated by oxidatively modified low density lipoprotein (LDL) or by the cytokines TNF alpha and IL-1, and (ii) the role of the adhesion molecules VCAM-1 and ICAM-1 (vascular cell and intercellular adhesion molecule, respectively) in this process. Preincubation of SMCs with both TNF alpha and IL-1 caused a significant 2-fold increase in VCAM-1 and ICAM-1 expression and a more than 9-fold increase in monocyte adhesion. The latter was significantly inhibited (by 1/3) by neutralising antibodies to VCAM-1 and ICAM-1. Modified LDL also induced a significant 3-fold increase in monocyte adhesion to SMCs, but did not induce VCAM-1 or ICAM-1 expression, nor was this adhesion inhibited by neutralising antibodies to VCAM-1 or ICAM-1. Oxidatively modified LDL, like the proinflammatory cytokines TNF alpha and IL-1, has the ability to enhance monocyte adhesion to human SMCs in vitro. LDL-induced monocyte adhesion to SMCs is distinct from that induced by TNF alpha and IL-1 in its lack of dependence on the classical adhesion pathways involving smooth muscle VCAM-1 and ICAM-1. SMCs are identified as a new cell population which may play an active role in recruiting monocytes to the arterial intima and atherosclerotic plaque.

Antibodies, Monoclonal↗
PubMed1996

Extent of oxidative modification of low density lipoprotein determines the degree of cytotoxicity to human coronary artery cells.

OBJECTIVE: To assess whether the extent of LDL oxidation influences its cytotoxic effects, thus contributing to its atherogenic potential. DESIGN AND SETTING: The effects of native and modified LDL on cultured human coronary artery smooth muscle cells (SMC) and endothelial cells (ECs) were investigated. MAIN OUTCOME MEASURES: Four indices of cytotoxicity were studied: (i) chromium-51 release; (ii) 5-bromo-2'-deoxyuridine (BrDUrd) uptake; (iii) morphological appearance; and (iv) EC migration. RESULTS: (i) Minimally modified (mm) LDL (400 micrograms/ml) causes significant 51Cr release; the cytotoxic effect was significantly greater for copper oxidised (ox) LDL (400 micrograms/ml). Native LDL had no effect. (ii) BrDUrd uptake studies showed significant inhibition of cell proliferation by 100 micrograms/ml of oxLDL and to a lesser extent by mmLDL; native LDL had no effect. (iii) Morphological appearance was not altered by native LDL. Changes in cell morphology were induced by mmLDL (400 micrograms/ml), and were more pronounced with oxLDL in concentrations of > or = 200 micrograms/ml. (iv) EC migration was significantly inhibited by oxLDL (100 micrograms/ml), but not by native or mmLDL. CONCLUSION: The extent of oxidation of LDL determined its cytotoxicity to coronary artery cells. Native LDL had no cytotoxic effect. In contrast, oxLDL and to a lesser extent mmLDL caused cytotoxicity at concentrations to which cells in vivo might be exposed. This may contribute to the atherogenicity of modified LDL by enhancing cellular injury and inflammation, and by inhibiting re-endothelialisation of areas of coronary artery damaged during the atherogenic process.

Bromodeoxyuridine↗
PubMed1994

Hepatic portal venous flow in patients undergoing tricuspid valve surgery.

OBJECTIVE: To determine the changes of flow in the hepatic artery and portal vein of patients undergoing tricuspid valve repair together with mitral valve replacement. DESIGN: Non-randomised parallel group study. SETTING: Tertiary referral centre. PATIENTS: 18 patients with mitral valve disease with or without tricuspid regurgitation (age range 46-73; six men) and six patients with coronary artery disease and normal left ventricular function (women age range 39-78; four men). INTERVENTIONS: Mitral valve replacement with or without modified De Vega repair of the tricuspid valve or coronary artery bypass surgery. MAIN OUTCOME MEASURES: Flow in the hepatic artery and portal vein as measured by duplex Doppler flowmetry before and two to four weeks after operation. RESULTS: Preoperative hepatic artery flow was less in patients with mitral valve disease than in patients with coronary artery disease (162.7(13.1) ml.min-1 v 242.5(6.6) ml.min-1, p < 0.05). Portal vein perfusion was significantly reduced only in patients with associated tricuspid regurgitation compared with (844(83) ml.min-1 v 1422(64) ml.min-1 p < 0.05). Hepatic perfusion was unaltered after operation in patients undergoing coronary artery bypass surgery (p > 0.05). Flow in the hepatic artery and portal vein was improved only in patients undergoing mitral valve replacement with associated tricuspid valve repair (p < 0.05). CONCLUSION: Abnormalities of hepatic perfusion can be measured non-invasively in all patients with mitral valve disease but especially in those with associated tricuspid regurgitation needing valve repair. These abnormalities improved two to four weeks after mitral valve surgery and tricuspid valve repair, suggesting that measurement of portal flow might be a useful means of assessing the severity of tricuspid regurgitation.

Adult↗
PubMed1994

Abnormal ventricular repolarisation in association with myocardial bridging.

Myocardial bridging causing systolic compression of epicardial coronary arteries may be an incidental finding at coronary arteriography. Bridging rarely causes myocardial ischaemia. A young man presented with chest pain and striking abnormalities of ventricular repolarisation that initially were treated as myocardial infarction. At cardiac catheterisation the coronary arteries were normal apart from the presence of a myocardial bridge affecting a major diagonal branch of the left anterior descending artery. Echocardiography was normal with no features of hypertrophic cardiomyopathy.

Adult↗
PubMed1990

Coronary arteriography in a district general hospital: feasibility, safety, and diagnostic accuracy.

OBJECTIVE: To determine the feasibility, safety, and diagnostic accuracy of coronary arteriography in the radiology department of a district general hospital using conventional fluoroscopy and videotape recording. DESIGN: Observational study of the feasibility and safety of coronary arteriography in a district general hospital and analysis of its diagnostic accuracy by prospective within patient comparison of the video recordings with cinearteriograms obtained in a catheter laboratory. SETTING: Radiology department of a district general hospital and the catheter laboratory of a cardiological referral centre. SUBJECTS: 50 Patients with acute myocardial infarction treated with streptokinase who underwent coronary arteriography in a district general hospital three (two to five) days after admission. 45 Of these patients had repeat coronary arteriography after four (three to seven) days in the catheter laboratory of a cardiological referral centre. MAIN OUTCOME MEASURES: Incidence of complications associated with catheterisation and the sensitivity and specificity of video recordings in the district general hospital (judged by two experienced observers) for identifying the location and severity of coronary stenoses. RESULTS: Coronary arteriograms recorded on videotape in the district general hospital were obtained in 47 cases and apart from one episode of ventricular fibrilation (treated successfully by cardioversion) there were no complications of the procedure. 45 Patients were transferred for investigation in the catheter laboratory, providing 45 paired coronary arteriograms recorded on videotape and cine film. The specificity of the video recordings for identifying the location and severity of coronary stenoses was over 90%. Sensitivity, however, was lower and for one observer fell below 40% for lesions in the circumflex artery. A cardiothoracic surgeon judged that only nine of the 47 video recordings were adequate for assessing revascularisation requirements. CONCLUSIONS: Coronary arteriography in the radiology department of a district general hospital is safe and feasible. Nevertheless, the quality of image with conventional fluoroscopy and video film is inadequate and will need to be improved before coronary arteriography in this setting can be recommended.

Aged↗
PubMed1990

Exertional myocardial ischemia in diabetes: a quantitative analysis of anginal perceptual threshold and the influence of autonomic function.

Patients with diabetes are prone to silent myocardial infarction and silent exertional ischemia. Although the mechanism is not clear, it may reflect a specific impairment of the sensory innervation of the heart. To test this hypothesis, anginal perceptual threshold was measured in 32 diabetic patients and 36 nondiabetic control patients, all of whom had typical exertional angina. Anginal perceptual threshold was defined as the time from onset of 0.1 mV ST depression to the onset of chest pain during treadmill stress electrocardiography. Although ST depression occurred earlier in the diabetic than in the nondiabetic group (111 +/- 82 versus 216 +/- 162 s, p less than 0.005), the anginal perceptual threshold in the diabetic group was delayed by a mean of 86 s (149 +/- 76 versus 63 +/- 59 s, p less than 0.001), with 95% confidence intervals of 53 to 119 s. Autonomic function tests were abnormal in the diabetic group, and in both groups regression analyses (using a third order polynomial) showed marked prolongations of anginal perceptual threshold as the heart rate responses to the Valsalva maneuver decreased to below the normal range (r = 0.5, p less than 0.001). There was a similar though less pronounced relation between anginal perceptual threshold and the heart rate responses to deep breathing (r = 0.3, p less than 0.02). These data suggest that prolongation of the anginal perceptual threshold may be caused by autonomic neuropathy involving the sensory innervation of the heart. To test sensory function, median nerve conduction studies were performed in 19 patients (10 diabetic and 9 nondiabetic).(ABSTRACT TRUNCATED AT 250 WORDS)

Angina Pectoris↗
PubMed1990

Prolonged anginal perceptual threshold in diabetes: effects on exercise capacity and myocardial ischemia.

Anginal perceptual threshold (the time from onset of 0.1 mV of ST segment depression to onset of angina during treadmill exercise) is prolonged in diabetic patients with coronary artery disease. In the present study, the functional significance of this perceptual abnormality was evaluated by analysis of its effect on exercise capacity and the severity of myocardial ischemia. Treadmill exercise in 32 diabetic patients and 36 nondiabetic control patients showed a close linear correlation between the time to onset of electrical ischemia (ST segment depression) and exercise capacity in both groups (r = 0.8 and 0.9, respectively; p less than 0.001). However, the slope of the relation was flatter in the diabetic group because prolongation of the anginal perceptual threshold permitted continued exercise as ischemia intensified. The anginal perceptual threshold itself showed a close linear correlation with exercise capacity in the diabetic group (r = 0.8, p less than 0.001), although in the nondiabetic group these variables were unrelated. The permissive effect of a prolonged anginal perceptual threshold on exercise capacity is undesirable as reflected by its correlation with ischemia at peak exercise (r = 0.6, p less than 0.001): the longer the threshold, the greater the exercise capacity and the more severe the ischemia. Indeed, the inverse relation between the severity of ischemia at peak exercise and exercise capacity in the nondiabetic group (r = 0.4, p less than 0.02) was completely lost in the diabetic group. Thus, in diabetic patients with coronary artery disease, anginal perceptual threshold is a major determinant of exercise capacity.(ABSTRACT TRUNCATED AT 250 WORDS)

Angina Pectoris↗
PubMed1989

Patterns of coronary artery disease in post-infarction ventricular septal rupture.

Cardiac angiography was reviewed in 91 patients with post-infarction ventricular septal rupture. The results were compared with those of 123 stable survivors who had a positive submaximal exercise test early after infarction. Anterior infarction and occlusion of the infarct vessel were more common in those with ventricular septal rupture than in the comparison group. In the group with ventricular septal rupture there was more left ventricular damage, with aneurysm formation in two thirds, and coronary angiography showed more single than triple vessel disease. In the comparison group there was more triple vessel disease than single vessel disease. Angiographically demonstrable collaterals to the infarct territory were not seen or only very faintly seen in 82% of those with septal rupture. Well developed collaterals were seen in two thirds of the comparison group. These patterns of coronary disease suggest that ventricular septal rupture is more likely in patients with coronary occlusion and little or no collateral support to the infarct territory.

Collateral Circulation↗
PubMed1989

Myocardial abscess and sternal osteomyelitis following myocardial infarction and resuscitation.

A 58 year old man presented with an anterior myocardial infarction requiring repeated resuscitation. He had impaired glucose tolerance. He died five weeks later and post-mortem examination revealed a myocardial abscess and sternal osteomyelitis due to Staphylococcus aureus. These had not been apparent clinically. The possible aetiology and difficulties in diagnosis are discussed.

Abscess↗
PubMed1988

Infective endocarditis: incidence and mortality in the North East Thames Region.

A survey of infective endocarditis in the North East Thames Regional Health Authority was carried out over a period of 30 months from 1982 to 1984. The incidence, clinical characteristics, and in-hospital mortality were studied. Important causes of endocarditis were dental treatment, the presence of dental disease, drug abuse, and cytoscopy. The omission or incorrect administration of antibiotic prophylaxis in patients with valve disease was noted, but failure of correctly prescribed antibiotic prophylaxis was not recorded. Adverse prognostic features were increased age, prosthetic valve infection, Gram negative or staphylococcal infections, and aortic valve involvement. In contrast, mortality was lower in patients with mitral valve prolapse, ventricular septal defect, and streptococcus viridans infection. Deaths were usually attributable to irreversible complications present at the time of diagnosis. Vegetations were detected on the echocardiogram in half of those studied and mortality was higher in those with vegetations than without. Operation for native valve infection was associated with a low mortality and it is likely that the overall mortality for infective endocarditis has been improved by surgical intervention.

Endocarditis, Bacterial↗
PubMed1988

Relative power of clinical, exercise test, and angiographic variables in predicting clinical outcome after myocardial infarction: the Newham and Tower Hamlets study.

The interrelations of clinical, exercise test, and angiographic variables and their relative values in predicting specific clinical outcomes after myocardial infarction have not been fully established. Of 302 consecutive stable survivors of infarction, 262 performed a predischarge submaximal exercise test. In the first year after infarction patients with a "positive" exercise test were 13 times more likely to die, 2.8 times more likely to have an ischaemic event, and 2.3 times more likely to develop left ventricular failure than patients with negative tests. Patients with positive exercise tests underwent cardiac catheterization. Features of the history, 12 lead electrocardiogram, in-hospital clinical course, exercise test, and left ventricular and coronary angiograms that predicted these clinical end points were identified by univariate analysis. Then multivariable analysis was used to assess the relative powers of all variables in predicting end points. Certain features of the exercise test remained independent predictors of future ischaemic events and the development of overt left ventricular failure, but clinical and angiographic variables were more powerful predictors of mortality. Because the exercise test is also used to select patients for angiography, however, the results of this study strongly support the use of early submaximal exercise testing after infarction.

Adult↗
PubMed1986

Effects of erythrapheresis on pulmonary haemodynamics and oxygen transport in patients with secondary polycythaemia and cor pulmonale.

Reducing packed cell volume has been advocated as a therapeutic procedure in patients with polycythaemia secondary to hypoxic cor pulmonale. The aim of this investigation was to evaluate the effects of this manoeuvre on resting pulmonary haemodynamics and tissue oxygenation in 12 such patients. The subjects were studied whilst they were breathing air (n = 12), after breathing 35% oxygen for 30 min (n = 11) and breathing air 30 min after isovolaemic reduction in packed cell volume, from 0.61 +/- 0.02 to 0.50 +/- 0.02 (mean +/- SEM), by erythrapheresis (n = 12). Initial values for the group were: PaO2 6.5 +/- 0.3 kPa; red cell mass 152 +/- 12% predicted; mean pulmonary artery pressure (PAP) 41 +/- 3 mmHg; cardiac index 3.1 +/- 0.31 min-1 m-2. Breathing 35% oxygen reduced PAP by 3.1 +/- 1.0 mmHg (P less than 0.02), cardiac index by 0.28 +/- 0.121 min-1 m-2 (P less than 0.05) and right ventricular stroke work by 0.05 +/- 0.01 J (P less than 0.01). Systemic vascular resistance was unchanged. Systemic oxygen transport increased and peripheral oxygen consumption was unaltered. Erythrapheresis reduced blood viscosity at shear rates 23 S-1 and 230 S-1. PAP fell by 2.4 +/- 1.1 mmHg (P less than 0.05) and cardiac index increased by 0.32 +/- 0.091 min-1 m-2 (P less than 0.01), but right ventricular stroke work was unchanged. Systemic vascular resistance was reduced by 25 +/- 7 kPa S l-1 (P less than 0.01). Systemic oxygen transport decreased but peripheral oxygen consumption was unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1985

Adverse effects of high dose aspirin on platelet adhesion to experimental autogenous vein grafts.

Prostacyclin (PGI2) production and platelet adhesion were studied in veins grafted into the arterial system of rabbits. Animal groups consisted of: no treatment; low dose aspirin (ASA) (0.5 mg . kg-1 X 24 h-1) plus dipyridamole (2 mg . kg-1 X 6 h-1); high dose ASA (40 mg . kg-1 X 24 h-1) plus dipyridamole (2 mg . kg-1 X 6 h-1); dipyridamole (2 mg . kg-1 X 6 h-1) alone. Results showed that vein grafts from animals treated with high dose ASA plus dipyridamole produced significantly less PGI2 than the other three groups (p less than 0.05 compared with the dipyridamole group; p less than 0.01 compared with the other two groups). In addition, there was significantly greater platelet deposition on the vein grafts from this high dose ASA group as compared to the low dose ASA group (p less than 0.05). By contrast, animals treated with dipyridamole alone had significantly less platelet deposition compared to both the control and high dose ASA groups (p less than 0.05). High dose ASA given to prevent thrombotic occlusion following coronary artery bypass grafting may, by reducing PGI2, result in enhanced platelet deposition. This in turn is likely to increase intimal hyperplasia as has been demonstrated previously with high dose ASA. Clinical studies, which have shown the early anti-thrombotic benefits of high dose ASA plus dipyridamole, have not measured graft intimal thickness. Since this process is an important cause of graft narrowing, ASA, in high dose, may adversely affect long-term graft survival.

6-Ketoprostaglandin F1 alpha↗